natriuretic-peptide--brain and Cardiomyopathies

Liver cirrhosis is an increasing public health problem and a major cause of morbidity and mortality. Accordingly, cirrhotic cardiomyopathy, a frequently underdiagnosed condition, is becoming a growing health problem. In the last 20 years, cardioselective biomarkers have been investigated for their diagnostic and prognostic properties for numerous conditions. The aim of this article is to review the literature on the relationship between the most commonly used cardioselective biomarkers (cardiac troponins I and T, N-terminal pro-B-type natriuretic peptide, brain natriuretic peptide, and heart-type fatty-acid binding protein) and the presence, functional stage, and clinical outcomes of liver cirrhosis. Elevated plasma levels of these biomarkers have been reported in patients with liver cirrhosis, and there is mounting evidence on their predictive value for clinical outcomes in this disease. In addition, elevated plasma levels of these biomarkers have been reported in patients before, during, and after liver transplantation, but in fewer studies. Due to their predictive value for clinical outcomes, we advocate the use of these markers in patients with liver cirrhosis and cirrhotic cardiomyopathy, as well as in candidates for liver transplant.

Topics: Biomarkers; Cardiomyopathies; Humans; Liver Cirrhosis; Liver Transplantation; Natriuretic Peptide, Brain; Public Health

Angiotensin receptor neprilysin inhibitors (ARNI), sodium-glucose cotransporter 2 inhibitors (SGLT2i), soluble guanylate cyclase stimulators (sGCs), and the traditional golden triangle standard-of-care (SOC) are effective drugs for heart failure. We aimed to assess the efficacy of 4 interventions in these patients.. PubMed, The Cochrane Library, Embase, and Web of Science databases were electronically searched to collect randomized controlled trials of 3 novel drugs in the treatment of heart failure from inception to September 1st, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk bias of included studies. Stata 16.0 software was used for network meta-analysis.. A total of 17 randomized controlled trial involving 38,088 patients were included. The results of network meta-analysis: in terms of heart failure rehospitalization rate, 3 novel drugs lower than SOC [ARNI (OR = 0.77, 95% CI: 0.71-0.83), SGLT2i (OR = 0.70, 95% CI: 0.63-0.77), sGCs (OR = 0.88, 95% CI: 0.78-0.99)], and SGLT2i was also lower than sGCs (OR = 0.79, 95% CI: 0.68-0.93). In terms of all-cause mortality, ARNI was lower than SOC (OR = 0.81, 95% CI: 0.66-0.99). In terms of cardiovascular mortality, ARNI and SGLT2i was lower than SOC (ARNI [OR = 0.80, 95% CI: 0.70-0.92], SGLT2i [OR = 0.87, 95% CI: 0.76-0.99]). In terms of rates of cardiovascular death or heart failure rehospitalization, 3 novel drugs lower than SOC (ARNI [OR = 0.76, 95% CI: 0.71-0.82], SGLT2i [OR = 0.76, 95% CI: 0.70-0.82], sGCs [OR = 0.87, 95% CI: 0.78-0.97]). In terms of Kansas city cardiomyopathy questionnaire score, ARNI and SGLT2i was superior to SOC (ARNI [MD = 1.43, 95% CI: 0.43-2.42], SGLT2i [MD = 1.88, 95% CI: 1.12-2.65]). In terms of N-terminal pro-B-type natriuretic peptide outcome indexes, SGLT2i was superior to SOC (MD = -134.63, 95% CI: -237.70 to -31.56). The results of Surface under the cumulative ranking sequencing: in terms of heart failure rehospitalization rate and rates of cardiovascular death or heart failure rehospitalization, the ranking was SGLT2i>ARNI>sGCs>SOC. in terms of all-cause mortality and cardiovascular mortality, the ranking was ARN>SGLT2i>sGCs>SOC. in terms of Kansas city cardiomyopathy questionnaire score and N-terminal pro-B-type natriuretic peptide outcome indexes, the ranking was SGLT2i>ARN>SOC.. The available evidence suggests that all 3 novel heart failure drugs can improve the prognosis of heart failure. ARNI may be the most effective in reducing mortality, SGLT2i may be the most effective in improving quality of life, while sGCs may be inferior to ARNI and SGLT2i.

Topics: Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Network Meta-Analysis; Quality of Life; Randomized Controlled Trials as Topic; Stroke Volume

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in the coronavirus 2019 (COVID-19) global pandemic. While primarily a respiratory virus, SARS-CoV-2 can cause myocardial injury. The pattern of injury, referred to as acute COVID-19 cardiovascular syndrome (ACovCS), is defined by cardiac troponin leak in the absence of obstructive coronary artery disease. Although the etiology of the injury is unknown, many speculate that a cytokine release syndrome (CRS) may be an important factor. We aim to review recent data concerning markers of cardiac injury in ACovCS and its relation to the CRS.. Cardiac injury was common in patients hospitalized for COVID-19, with both cardiac troponin and B-type natriuretic peptide (BNP) being elevated in this population. Biomarkers were correlated with illness severity and increased mortality. Cytokines such as IL-6 were more often elevated in patients with ACovCS. Myocarditis evident on cardiac MR following COVID-19 may be associated with cardiac troponin levels. The impact of dexamethasone and remdesivir, two therapies shown to have clinical benefit in COVID-19, on myocardial injury is unknown. Biomarkers of cardiac stress and injury in COVID-19 may be used to stratify risk in the future. Currently, there is no evidence that inhibition of cytokine release will reduce myocardial injury in patients with COVID-19.

Topics: Biomarkers; Cardiomyopathies; COVID-19; Cytokine Release Syndrome; Humans; Natriuretic Peptide, Brain; SARS-CoV-2; Troponin

An increase in left ventricular volume after a myocardial infarction is a key component of the adverse remodelling process leading to chamber dysfunction, heart failure and an unfavourable outcome. Hence, the therapeutic strategies have been designed to reverse the remodelling process by medical therapy, devices or surgical strategies. Surgical ventricular reconstruction primarily combined with myocardial revascularization has been introduced as an optional intervention aimed to reduce the left ventricle through resection of the scar tissue and is recommended in selected patients with predominant heart failure symptoms, and with myocardial scarring and moderate left ventricular remodelling. This review outlines the rationale and the technique for reconstructing the left ventricle and the possible indications for using that technique, based on experiences from the centre with the largest international experience. The major contributions in the literature are briefly discussed.

Topics: Biomarkers; Cardiomyopathies; Contraindications, Procedure; Heart Ventricles; Humans; Mitral Valve; Mitral Valve Insufficiency; Myocardial Ischemia; Natriuretic Peptide, Brain; Patient Selection; Peptide Fragments; Ventricular Remodeling

Heart failure with left ventricular dysfunction occurring during pregnancy or during the post-partum period in patients without history of cardiovascular disease defines peripartum cardiomyopathy (PPCM). PPCM carries a high morbidity and mortality rate as well as the possibility of recovery ad integrum. Its incidence shows ethnic variations, with a greater prevalence of the disease among women with African descent. Pathogenesis of PPCM remains poorly understood. Both "oxidative stress-prolactin axis" and "anti-angiogenic-signaling excess" hypotheses are currently being investigated. Novel diagnostic strategies and biomarkers are currently being evaluated. Besides conventional treatment of heart failure, targeted therapies such as pharmacological prolactin blockade are under evaluation. The aim of this short review is to highlight current management as targeted therapy has far been disappointing.

Topics: Bromocriptine; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Heart Failure; Heart Transplantation; Heart-Assist Devices; Hormone Antagonists; Humans; Incidence; Natriuretic Peptide, Brain; Oxidative Stress; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prolactin; Radiography, Thoracic; Ventricular Dysfunction, Left

Cardiac biomarkers have been extensively investigated as early detectors of cardiac toxicity from cancer therapies. Whereas the role of biomarkers in monitoring anthracycline toxicity is generally well understood, substantial uncertainty remains regarding their role in monitoring newer targeted cancer therapies.. This review article examines all major published studies using cardiac troponins and/or N-terminal pro-B-type natriuretic peptide (NT-proBNP) in monitoring for cardiac toxicity with trastuzumab, tyrosine kinase inhibitors, and mammalian target of rapamycin (mTOR) inhibitors. There is substantial variability among studies regarding biomarker assays used, sensitivity of the assays, and definitions of abnormal results. In general, troponin I predicts early but not late cardiac events when trastuzumab is administered after anthracyclines, but troponin increases likely reflect anthracycline injury rather than trastuzumab injury. NT-proBNP detects cardiac toxicity with tyrosine kinase inhibitors and mTOR inhibitors, but not independently from echocardiography.. Troponin I can serve as a marker for susceptibility to cardiac toxicity during early trastuzumab treatment in patients who have received recent anthracyclines. NT-proBNP can serve as a useful marker of cardiac toxicity in patients treated with tyrosine kinase inhibitors or mTOR inhibitors if echocardiographic screening is not being used.

Topics: Antineoplastic Agents; Biomarkers; Cardiomyopathies; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin I

Sepsis-induced myocardial dysfunction is a common complication in septic patients and is associated with increased mortality. In the clinical setting, it was once believed that myocardial dysfunction was not a major pathological process in the septic patients, at least in part, due to the unavailability of suitable clinical markers to assess intrinsic myocardial function during sepsis. Although sepsis-induced myocardial dysfunction has been studied in clinical and basic research for more than 30 years, its pathophysiology is not completely understood, and no specific therapies for this disorder exist. The purpose of this review is to summarize our current knowledge of sepsis-induced myocardial dysfunction with a special focus on pathogenesis and clinical characteristics.

Topics: Biomarkers; Blood Pressure; Calcium; Cardiomyopathies; Electrocardiography; Heart; Humans; Natriuretic Peptide, Brain; Sepsis

The natural history of immunoglobulin light chain associated amyloidosis (AL) is determined by the extent of cardiac involvement. Patients with cardiac AL and symptomatic heart failure have a median survival of approximately six months without successful treatment of the underlying plasma cell disorder The outcome in cardiac AL is determined by both the severity of cardiac involvement and the response to treatment. Staging systems using cardiac biomarkers, including NT- proBNP and troponin, have been found to be powerful predictors of prognosis and are used to guide treatment. Arrhythmias are common in cardiac AL and may lead to acute hemodynamic compromise. Sudden cardiac death, often due to pulseless electrical activity, is an important cause of early mortality. Supportive therapy for heart failure is usually limited to diuretics. Beta-blockers, ACE-inhibitors, and angiotensin receptor blockers are poorly tolerated in cardiac AL and should be avoided. Cardiac transplantation is controversial and reserved for highly selected patients with limited extracardiac involvement. The primary target of treatment in cardiac AL is obliteration of the plasma cell clone, using chemotherapy alone or combined with autologous stem cell transplantation. Despite the risk of early mortality, overall survival has improved with advances in disease modifying therapy. Earlier diagnosis and treatment of cardiac AL is crucial to improving survival.

Topics: Aged; Amyloidosis; Atrial Fibrillation; Biomarkers; Cardiomyopathies; Death, Sudden, Cardiac; Early Diagnosis; Female; Heart Failure; Heart Transplantation; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Embolism; Troponin

Cardiac involvement drives the prognosis and treatment in systemic amyloid. Echocardiography, the mainstay of current cardiac imaging, defines cardiac structure and function. Echocardiography, in conjunction with clinical phenotype, electrocardiogram and biomarkers (brain natriuretic peptide and troponin), provides an assessment of the likelihood and extent of cardiac involvement. Two tests are transforming our understanding of cardiac amyloidosis, bone tracer scanning and cardiovascular magnetic resonance (CMR). CMR provides a "second opinion" on the heart's structure and systolic function with better accuracy and more precision than echocardiography but is unable to assess diastolic function and is not as widely available. Where CMR adds unique advantages is in evaluating myocardial tissue characterisation. With administration of contrast, the latest type of late gadolinium enhancement imaging (phase-sensitive inversion recovery sequence) is highly sensitive and specific with images virtually pathognomonic for amyloidosis. CMR is also demonstrating that the range of structural and functional changes in cardiac amyloid is broader than traditionally thought. CMR with T1 mapping, a relatively new CMR technique, can measure the amyloid burden and the myocyte response to infiltration (hypertrophy/cell loss) with advantages for tracking change (e.g. the wall thickness can stay the same but the composition can change) over time or during therapy. Such techniques hold great promise for advancing drug development in this arena and providing new prognostic insights. CMR with tissue characterisation is rewriting our understanding of cardiac amyloidosis and may lead to the development of new classification, therapies and prognostic systems.

Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Contrast Media; Echocardiography; Gadolinium; Humans; Magnetic Resonance Imaging; Myocardium; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Troponin

Cardiac manifestations are recognized complications of subarachnoid hemorrhage. Neurogenic stress cardiomyopathy is one complication that is seen in acute subarachnoid hemorrhage. It can present as transient diffuse left ventricular dysfunction or as transient regional wall motion abnormalities. It occurs more frequently with neurologically severe-grade subarachnoid hemorrhage and is associated with increased morbidity and poor clinical outcomes. Managing this subset of patients is challenging. Early identification followed by a multidisciplinary team approach can potentially improve outcomes.

Topics: Adrenergic beta-Antagonists; Apoptosis; Cardiomyopathies; Cardiotonic Agents; Catecholamines; Electrocardiography; Humans; Intra-Aortic Balloon Pumping; Myocytes, Cardiac; Natriuretic Peptide, Brain; Prognosis; Subarachnoid Hemorrhage; Troponin I; Ventricular Dysfunction, Left

Peripartum cardiomyopathy is a form of heart failure occurring at the end of pregnancy or early in the postpartum period. Women may recover, have persistent cardiac dysfunction or suffer complications and death. Women who are African-American, older, hypertensive or have multiple gestation pregnancies have increased risk. Diagnosis and treatment may be delayed due to similarities between symptoms of normal pregnancy and heart failure. Echocardiography is essential for the diagnosis, and B-type natriuretic peptide can be helpful. Treatment for systolic heart failure must be adjusted during pregnancy, and anticoagulation may be indicated. Even after recovery, subsequent pregnancy confers substantial risk of worsening heart failure. Further investigations into the etiology, duration of treatment and risks for relapse are needed.

Topics: Age Factors; Black or African American; Breast Feeding; Cardiomyopathies; Cardiovascular Agents; Echocardiography; Female; Humans; Hypertension; Multiple Birth Offspring; Natriuretic Peptide, Brain; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Risk Factors; United States

Topics: Biomarkers; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Neurotransmitter Agents; Prognosis; Risk Factors

AL amyloidosis patients with multi-organ and particularly cardiac involvement have historically been considered to have a bad prognosis. The introduction of autologous stem cell transplantation was associated with unacceptable toxicity in high-risk patients, but responding patients have prolonged overall survival. Toxicities can be decreased by careful patient selection, but this reduces the applicability of this treatment modality to a limited number of patients. Efforts are therefore needed to design novel more effective regimens, with the use of new medications, such as thalidomide, lenalidomide and bortezomib, next generation immunomodulatory drugs and proteasome inhibitors. Their combination with dexamethasone and alkylating agents show promising results, allowing a high percentage of remission and subsequent event-free and overall survival, even in a significant proportion of high risk, poor prognosis populations. This review includes the state-of-the-art treatment for AL amyloidosis patients as of 2012, in light of the progress in management of this disease during recent years.

Topics: Alkylating Agents; Amyloid; Amyloidosis; Biomarkers; Boronic Acids; Bortezomib; Cardiomyopathies; Clinical Trials as Topic; Combined Modality Therapy; Dexamethasone; Forecasting; Humans; Immunoglobulin Light Chains; Immunologic Factors; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pyrazines; Risk; Severity of Illness Index; Stem Cell Transplantation; Troponin C; Troponin T

Brain natriuretic peptide (BNP) and N-terminal brain natriuretic peptide (NT-proBNP) are important biomarkers for pediatric cardiovascular diseases. Peptide levels are associated with age and gender. Current studies have shown that BNP and NT-proBNP are valuable in the diagnosis of heart failure, with a high specificity and sensitivity. They also contribute to differentiating heart failure from acute respiratory distress induced by simple pulmonary factors. In addition, BNP and NT-proBNP are useful in the evaluation of disease severity and treatment guidance in children with pulmonary hypertension, cardiomyopathy and Kawasaki disease. Current limitations include the relatively small sample size of the study, the detection method and a range of normal values that are not completely uniform.

Topics: Cardiomyopathies; Cardiovascular Diseases; Child; Dyspnea; Familial Primary Pulmonary Hypertension; Heart Failure; Humans; Hypertension, Pulmonary; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Peptide Fragments

Pulmonary hypertension (PH) is a well-recognized complication of sarcoidosis. Patients with sarcoidosis-associated PH (SAPH) have poorer functional status and greater supplemental oxygen requirements than sarcoidosis patients without PH, and are more likely to be listed for lung transplantation. PH is an independent risk factor for mortality in sarcoidosis patients awaiting lung transplantation. The pathophysiology of SAPH is complex, with multiple mechanisms contributing to pathogenesis, including the fibrous destruction of the pulmonary vascular bed, extrinsic compression of the central pulmonary vessels and an intrinsic vasculopathy. Recognition of SAPH may be delayed as it can be masked by the clinical picture of underlying pulmonary sarcoidosis, and right heart catheter remains the gold-standard for diagnosis. Management of SAPH is based on reversal of resting hypoxaemia, treatment of comorbidities and treatment of the underlying sarcoidosis. The use of corticosteroids in SAPH is controversial. Specific PH therapy is not routinely recommended in SAPH as there are no successful placebo-controlled trials, although there is limited data to suggest that endothelin receptor antagonists and phosphodiesterase-5 inhibitors may be useful.

Topics: Cardiomyopathies; Endothelin-1; Humans; Hypertension, Pulmonary; Lung; Natriuretic Peptide, Brain; Sarcoidosis, Pulmonary; Ultrasonography; Vasoconstriction

Systemic AL amyloidosis is a rare complication of monoclonal gammopathies. Renal manifestations are frequent, mostly characterized by heavy proteinuria, with nephrotic syndrome and renal failure in more than half of the patients at diagnosis. Without treatment, median survival does not exceed 12 months. Amyloid heart disease and diffusion of amyloid deposits are associated with reduced survival. Treatment of systemic AL amyloidosis has been profoundly modified with the introduction of international criteria for the definition of organ involvement and hematologic response, and with the use of sensitive tests for the measurement of serum-free light chain levels. Melphalan plus dexamethasone is now established as the gold standard for first line treatment of systemic AL, with similar efficacy and reduced treatment-related mortality compared to high-dose therapy. Modern chemotherapy regimens, based on the use of novel agents such as bortezomib and lenalidomide, might further improve patient survival.

Topics: Amyloid; Amyloidosis; Biomarkers; Boronic Acids; Bortezomib; Cardiomyopathies; Consensus Development Conferences as Topic; Dexamethasone; Drug Therapy, Combination; Heart Transplantation; Humans; Immunoglobulin Light Chains; Kaplan-Meier Estimate; Kidney Failure, Chronic; Kidney Transplantation; Lenalidomide; Melphalan; Natriuretic Peptide, Brain; Paraproteinemias; Paraproteins; Peptide Fragments; Prognosis; Pyrazines; Randomized Controlled Trials as Topic; Renal Dialysis; Thalidomide

Amyloidotic cardiomyopathy (ACMP) occurs in the setting of rare genetic diseases, blood dyscrasias, chronic infection and inflammation, and advanced age. Cardiologists are on the front lines of diagnosis of ACMP when evaluating patients with unexplained dyspnea, congestive heart failure, or arrhythmias. Noninvasive detection of diastolic cardiac dysfunction and unexplained left ventricular hypertrophy should be followed by biopsy to demonstrate the presence of amyloid deposits and appropriate genetic, biochemical, and immunologic testing to accurately define the type of amyloid. Growing numbers of treatment options exist for these diseases, and timely diagnosis and institution of therapy is essential for preservation of cardiac function.

Topics: Amyloid; Amyloidosis; Biomarkers; Biopsy; Cardiomyopathies; Clinical Trials as Topic; Combined Modality Therapy; Diagnosis, Differential; Echocardiography; Electrocardiography; Humans; Myocardium; Natriuretic Peptide, Brain; Severity of Illness Index; Troponin T; Ventricular Function, Left

Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Cardiac Resynchronization Therapy; Cardiomyopathies; Chronic Disease; Diagnostic Imaging; Heart Failure; Humans; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain

Peripartum cardiomyopathy (PPCM) is a cause of pregnancy-associated heart failure. It typically develops during the last month of, and up to 6 months after, pregnancy in women without known cardiovascular disease. The present position statement offers a state-of-the-art summary of what is known about risk factors for potential pathophysiological mechanisms, clinical presentation of, and diagnosis and management of PPCM. A high index of suspicion is required for the diagnosis, as shortness of breath and ankle swelling are common in the peripartum period. Peripartum cardiomyopathy is a distinct form of cardiomyopathy, associated with a high morbidity and mortality, but also with the possibility of full recovery. Oxidative stress and the generation of a cardiotoxic subfragment of prolactin may play key roles in the pathophysiology of PPCM. In this regard, pharmacological blockade of prolactin offers the possibility of a disease-specific therapy.

Topics: Antihypertensive Agents; Cardiology; Cardiomyopathies; Cathepsin D; Europe; Female; Humans; Incidence; Inflammation; Natriuretic Peptide, Brain; Oxidative Stress; Postpartum Period; Pregnancy; Pregnancy Complications; Prognosis; Prolactin; Risk Factors; Societies, Medical

The prevalence of primary (hereditary) hemochromatosis and secondary iron overload (hemosiderosis) is reaching epidemic levels worldwide. Iron-overload leads to excessive iron deposition in a wide variety of tissues, including the heart and endocrine tissues.. Iron-overload cardiomyopathy is the primary determinant of survival in patients with secondary iron overload, while also being a leading cause of morbidity and mortality in patients with primary hemochromatosis. Iron-induced cardiovascular injury also occurs in acute iron toxicosis (iron poisoning), myocardial ischemia-reperfusion injury, cardiomyopathy associated with Friedreich ataxia, and vascular dysfunction. The mainstay therapies for iron overload associated with primary hemochromatosis and secondary iron overload is phlebotomy and iron chelation therapy, respectively. L-type Ca(2+) channels provide a high-capacity pathway for ferrous (Fe(2+)) uptake into cardiomyocytes in iron-overload conditions; calcium channel blockers may represent a new therapeutic tool to reduce the toxic effects of excess iron.. Iron-overload cardiomyopathy is a an important and potentially reversible cause of heart failure at an international scale and involves diastolic dysfunction, increased susceptibility to arrhythmias and a late-stage dilated cardiomyopathy. The early diagnosis of iron-overload cardiomyopathy is critical since the cardiac dysfunction is reversible if effective therapy is introduced before the onset of overt heart failure.

Topics: Anemia; Antioxidants; Biopsy; Calcium Channel Blockers; Cardiomyopathies; Chelation Therapy; Echocardiography; Endocardium; Endothelium, Vascular; Ferritins; Genetic Testing; Humans; Hypertension, Pulmonary; Iron Overload; Magnetic Resonance Imaging, Cine; Natriuretic Peptide, Brain; Phlebotomy; Transferrin; Ventricular Dysfunction, Right

Peripartum cardiomyopathy (PPCM) is a rare but potentially lethal complication of pregnancy occurring in approximately 1 : 3,000 live births in the United States although some series report a much higher incidence. African-American women are particularly at risk. Diagnosis requires symptoms of heart failure in the last month of pregnancy or within five months of delivery in the absence of recognized cardiac disease prior to pregnancy as well as objective evidence of left ventricular systolic dysfunction. This paper provides an updated, comprehensive review of PPCM, including emerging insights into the etiology of this disorder as well as current treatment options.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anticoagulants; Cardiomyopathies; Cytokines; Dyspnea; Edema; Electrocardiography; Female; Humans; Natriuretic Peptide, Brain; Pregnancy; Pregnancy Complications, Cardiovascular; Prognosis; Puerperal Disorders; Risk Factors; Stroke Volume; Tachycardia; Troponin T; Ventricular Dysfunction, Left

Interactions of glucose metabolism and chronic heart failure have been confirmed by many epidemiologic studies. The association of HbA1c with an increasing risk of heart failure clearly underlines the connection between both diseases. Coronary artery disease (CAD), hypertension and diabetic cardiomyopathy are long-term complications of diabetes mellitus, resulting in diabetic heart failure. Dysfunction of many regulation systems leads to specific diabetic cardiomyopathy, which has been firstly described by Rubler. A reduction in the cardiac expression of the Na-Ca exchanger pump and SERCA2a protein results in an imbalance in cardiac calcium handling. The overactive renin angiotensin aldosteron system (RAAS) also contributes to the impairment of myocardial function. Hyperlipidaemia, hpyerinsulinaemia and hyperglycaemia directly trigger diabetic cardiomyopathy. Generally chronic heart failure is a clinical diagnosis verified by blood tests like NT-proBNP and cardiac ultrasound. Recommendations on treatment of diabetic heart failure are based on subgroup analysis of the large heart failure trials.

Topics: Animals; Apoptosis; Autonomic Nervous System Diseases; Calcium; Cardiomyopathies; Coronary Disease; Cytokines; Diabetes Complications; Diabetic Neuropathies; Heart Failure; Homeostasis; Humans; Hyperglycemia; Hyperlipidemias; Hypertension; Mitochondria, Heart; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress

Cardiomyopathy is an anatomic and pathologic diagnosis associated with muscle or electrical dysfunction of the heart. Cardiomyopathies represent a heterogeneous group of diseases that often lead to progressive heart failure with significant morbidity and mortality. Cardiomyopathies may be primary (i.e., genetic, mixed, or acquired) or secondary (e.g., infiltrative, toxic, inflammatory). Major types include dilated cardiomyopathy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. Although cardiomyopathy is asymptomatic in the early stages, symptoms are the same as those characteristically seen in any type of heart failure and may include shortness of breath, fatigue, cough, orthopnea, paroxysmal nocturnal dyspnea, and edema. Diagnostic studies include B-type natriuretic peptide levels, baseline serum chemistries, electrocardiography, and echocardiography. Treatment is targeted at relieving the symptoms of heart failure and reducing rates of heart failure-related hospitalization and mortality. Treatment options include pharmacotherapy, implantable cardioverter-defibrillators, cardiac resynchronization therapy, and heart transplantation. Recommended lifestyle changes include restricting alcohol consumption, losing weight, exercising, quitting smoking, and eating a low-sodium diet.

Topics: Algorithms; Antihypertensive Agents; Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Risk Reduction Behavior

Cardiovascular disease is the leading cause of death among patients with Type 2 diabetes mellitus. The main forms of structural heart disease associated with diabetes are coronary heart disease and diabetic cardiomyopathy, which is characterized by left ventricular hypertrophy, left ventricular diastolic and systolic dysfunction. Asymptomatic structural heart disease is common and associated with a poor prognosis in patients with diabetes. Contemporary practice guidelines do not recommend screening of asymptomatic individuals for structural heart disease. Potential screening modalities, such as echocardiography, are costly and inaccessible. A simple, inexpensive blood test for brain natriuretic peptide is a useful marker of structural heart disease and is a prime candidate for screening patients with Type 2 diabetes mellitus and prioritizing referral for echocardiography.

Topics: Biomarkers; Cardiomyopathies; Diabetes Mellitus, Type 2; Echocardiography; Humans; Hypertrophy, Left Ventricular; Myocardial Ischemia; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Diagnostic Imaging; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis

Obesity is associated with an increased risk of heart failure. Apparently healthy obese individuals can, however, exhibit subclinical left ventricular dysfunction. The use of myocardial imaging techniques to detect this subclinical change could have important management implications with respect to initiating prophylactic therapy. In this Review, we evaluate possible pharmacologic and nonpharmacologic strategies for treating obesity cardiomyopathy in the context of currently understood mechanisms, including myocardial remodeling and small vessel disease, and more speculative mechanisms such as insulin resistance, and activation of the renin-angiotensin-aldosterone and sympathetic nervous systems.

Topics: Animals; Anti-Obesity Agents; Bariatric Surgery; Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Renin-Angiotensin System; Sympathetic Nervous System; Ventricular Dysfunction, Left; Weight Loss

Topics: Biomarkers; Biopsy; C-Reactive Protein; Cardiomyopathies; Early Diagnosis; Female; Heart-Assist Devices; Humans; Incidence; Natriuretic Peptide, Brain; Parity; Postnatal Care; Pregnancy; Pregnancy Complications, Cardiovascular; Prenatal Care; Prognosis; Puerperal Disorders; Rare Diseases; Risk Factors; Treatment Outcome; Troponin; United States

Brain natriuretic peptide (BNP) was isolated originally from porcine brain extracts but was soon defined as a cardiac natriuretic hormone. Together with the highly homologous atrial natriuretic peptide, it forms a dual natriuretic peptide system of the heart. The main stimulus for proBNP synthesis and secretion from cardiac myocytes is myocyte stretch. On secretion, the propeptide is split into the biologically active BNP and the remaining part of the prohormone N-terminal proBNP (NT-proBNP). In heart failure increased wall stretch, neurohormonal activation and hypoxia stimulate BNP secretion. The recently demonstrated production of BNP by stimulated cardiac fibroblasts is of uncertain pathophysiologic importance. In contrast to atrial natriuretic peptide, BNP is a constitutively secreted hormone with relatively little intracellular storage of mature peptide. In the normal state, the atrium is the main cardiac production site, but as heart failure develops, there is a profound activation of ventricular NT-proBNP synthesis. BNP acts on distant tissues and causes diuresis, vasodilatation, and decreased renin and aldosterone secretion. Known mechanisms of BNP clearance from plasma include binding to the natriuretic peptide clearance receptor type-C and proteolysis by peptidase NEP 24.11. NT-proBNP has a longer half-life and thus higher plasma concentration than BNP. It probably is cleared from plasma by renal excretion and possibly other unknown pathways.

Topics: Animals; Biomarkers; Cardiomyopathies; Humans; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors

The authors give a brief summary about the process and significance of cardiotoxicity produced by chemotherapy and irradiation used for malignancy. After the introduction, those invasive and noninvasive processes are put into focus and explained in detail, which are applied in the research of the effects of cardiotoxic chemotherapy. The clinical importance of this research is the life prolongation effect of the treatment, which allows the late-appearing toxic cardiomyopathy, resulting in congestive heart failure and increasing mortality. Summarizing the last decade's progress in research, it is evident that even in the planning of chemotherapy, the cardiovascular risks have to be taken into account, because they can greatly influence the cardiac side effect of the treatment.

Topics: Antineoplastic Agents; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Diastole; Electrocardiography; Heart Failure; Heart Rate; Humans; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Radionuclide Ventriculography; Systole; Ventricular Function, Left

During the past two decades, the heart has been known to undergo endocrine action, harbouring peptides with hormonal activities. These, termed "atrial natriuretic peptide (ANP)," "brain natriuretic peptide (BNP)," and "C-type natriuretic peptide (CNP)," are polypeptides mainly produced in the cardiac myocardium, where they are released into the circulation, producing profound hypotensive effects due to their diuretic, natriuretic, and vascular dilatory properties. It is, furthermore, well established that cardiac disorders such as congestive heart failure and different forms of cardiomyopathy are combined with increased expression of ANP and BNP, leading to elevated levels of these peptides in the plasma. Besides the occurrence of natriuretic peptides (NPs) in the ordinary myocardium, the presence of ANP in the cardiac conduction system has been described. There is also evidence of ANP gene expression in nervous tissue such as the nodose ganglion and the superior cervical ganglion of the rat, ganglia known to be involved in the neuronal regulation of the heart. Furthermore, in the mammalian heart, ANP appears to affect the cardiac autonomic nervous system by sympathoinhibitory and vagoexcitatory actions. This article provides an overview of the relationship between the cardiac conduction system, the cardiac innervation and NPs in the mammalian heart and provides data for the concept that ANP is also involved in neuronal cardiac regulation.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Heart; Heart Conduction System; Heart Failure; Humans; Immunohistochemistry; Mammals; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nodose Ganglion; Receptors, Atrial Natriuretic Factor; Superior Cervical Ganglion

One of the most common and life-threatening cardiovascular complications of HIV-infection is severe global left ventricular dysfunction due to primary heart muscle disease. At present, there is no single, cost-effective and reliable method of identifying the highly prevalent HIV-related cardiac dysfunction. Nonetheless, growing evidence supports the hypothesis that brain natriuretic peptide measurement has the potential to detect patients who develop HIV-related cardiomyopathy. If true, this hypothesis would have important clinical and public health implications.

Topics: Animals; Biomarkers; Cardiomyopathies; HIV Infections; Humans; Natriuretic Peptide, Brain

Guanylyl cyclases (GC) exist as soluble and particulate, membrane-associated enzymes which catalyse the conversion of GTP to cGMP, an intracellular signalling molecule. Several membrane forms of the enzyme have been identified up to now. Some of them serve as receptors for the natriuretic peptides, a family of peptides which includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP), three peptides known to play important roles in renal and cardiovascular physiology. These are transmembrane proteins composed of a single transmembrane domain, a variable extracellular natriuretic peptide-binding domain, and a more conserved intracellular kinase homology domain (KHD) and catalytic domain. GC-A, the receptor for ANP and BNP, also named natriuretic peptide receptor-A or -1 (NPR-A or NPR- 1), has been studied widely. Its mode of activation by peptide ligands and mechanisms of regulation serve as prototypes for understanding the function of other particulate GC. Activation of this enzyme by its ligand is a complex process requiring oligomerization, ligand binding, KHD phosphorylation and ATP binding. Gene knockout and genetic segregation studies have provided strong evidence for the importance of GC-A in the regulation of blood pressure and heart and renal functions. GC-B is the main receptor for CNP, the latter having a more paracrine role at the vascular and venous levels. The structure and regulation of GC-B is similar to that of GC-A. This chapter reviews the structure and roles of GC-A and GC-B in blood pressure regulation and cardiac and renal pathophysiology.

Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Blood Volume; Cardiomyopathies; Down-Regulation; Guanylate Cyclase; Heart Failure; Humans; Hypertension; Isoenzymes; Natriuretic Peptide, Brain; Receptors, Enterotoxin; Receptors, Guanylate Cyclase-Coupled; Receptors, Peptide; Structure-Activity Relationship

Several anticancer drugs have been associated with cardiac toxicity, especially the anthracyclines and trastuzumab. The pathogenesis of anthracycline-associated toxicity has been well described, whereas the mechanism of trastuzumab-associated toxicity is unknown. Although routine cardiac imaging studies (e.g. echocardiogram or multiple gated acquisition scans) may identify subclinical evidence of myocardial dysfunction, available data do not support their routine use for monitoring asymptomatic patients undergoing cancer therapy. Other modalities such as nuclear medicine scintigraphy with indium-111-antimyosin antibody and endomyocardial biopsy have been shown to be useful in identifying early cardiac damage, but their routine use is limited by practical considerations such as feasibility and cost. Consequently, there is significant interest in developing simple and reproducible methods for identifying patients at risk for treatment-induced myocardial damage. Available data suggest that circulating markers such as troponins and natriuretic peptides could potentially be useful for this purpose. Measurement of plasma troponin levels are commonly used in clinical practice in order to provide diagnostic and prognostic information in patients with myocardial ischaemia. Elevated levels may likewise correlate with anthracycline-induced cardiac damage, although plasma levels are only minimally elevated (well below that associated with ischaemia), and elevations may persist for weeks or months after anthracycline exposure. Clinical trials are currently evaluating the role of these markers in predicting both early and late, clinical and subclinical damage associated with anthracyclines and trastuzumab.

Topics: Antibiotics, Antineoplastic; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Neoplasms; Trastuzumab; Troponin T

The advances in cardiac failure are permanent. In 2000, once again, they concerned all fields of pathology. Complementary information of the epidemiology of the disease in France and Europe has been published. The prevention of sudden death by the implantable defibrillator in hypertrophic cardiomyopathy has been confirmed. The prognostic role of the aetiology of dilated cardiomyopathy has been demonstrated and the distinct clinical entity of acute fulminating viral myocarditis with an excellent long-term prognosis has been identified. New genetic abnormalities have been found in different forms of dilated cardiomyopathy. One of the most important advances concerns the neurohormones and the rise of interest in type B natriuretic peptide, for diagnosis, prognosis, as well as treatment (nesiritide). From the therapeutic point of view, the importance of betablockers has been confirmed, including in severe cardiac failure. The therapeutic value of biventricular stimulation resynchronising the two ventricles seem to be an additional therapeutic opportunity for patients with advanced cardiac failure. The summit of 2000 remains the first cellular transplantation carried out by a Parisian French team.

Topics: Cardiomyopathies; Cell Transplantation; Heart Failure; Humans; Natriuretic Peptide, Brain

Hereditary transthyretin-mediated (hATTR) amyloidosis is a rapidly progressive, multisystem disease that presents with cardiomyopathy or polyneuropathy. The APOLLO study assessed the efficacy and tolerability of patisiran in patients with hATTR amyloidosis. The effects of patisiran on cardiac structure and function in a prespecified subpopulation of patients with evidence of cardiac amyloid involvement at baseline were assessed.. APOLLO was an international, randomized, double-blind, placebo-controlled phase 3 trial in patients with hATTR amyloidosis. Patients were randomized 2:1 to receive 0.3 mg/kg patisiran or placebo via intravenous infusion once every 3 weeks for 18 months. The prespecified cardiac subpopulation comprised patients with a baseline left ventricular wall thickness ≥13 mm and no history of hypertension or aortic valve disease. Prespecified exploratory cardiac end points included mean left ventricular wall thickness, global longitudinal strain, and N-terminal prohormone of brain natriuretic peptide. Cardiac parameters in the overall APOLLO patient population were also evaluated. A composite end point of cardiac hospitalizations and all-cause mortality was assessed in a post hoc analysis.. In the cardiac subpopulation (n=126; 56% of total population), patisiran reduced mean left ventricular wall thickness (least-squares mean difference ± SEM: -0.9±0.4 mm, P=0.017), interventricular septal wall thickness, posterior wall thickness, and relative wall thickness at month 18 compared with placebo. Patisiran also led to increased end-diastolic volume (8.3±3.9 mL, P=0.036), decreased global longitudinal strain (-1.4±0.6%, P=0.015), and increased cardiac output (0.38±0.19 L/min, P=0.044) compared with placebo at month 18. Patisiran lowered N-terminal prohormone of brain natriuretic peptide at 9 and 18 months (at 18 months, ratio of fold-change patisiran/placebo 0.45, P<0.001). A consistent effect on N-terminal prohormone of brain natriuretic peptide at 18 months was observed in the overall APOLLO patient population (n=225). Median follow-up duration was 18.7 months. The exposure-adjusted rates of cardiac hospitalizations and all-cause death were 18.7 and 10.1 per 100 patient-years in the placebo and patisiran groups, respectively (Andersen-Gill hazard ratio, 0.54; 95% CI, 0.28-1.01).. Patisiran decreased mean left ventricular wall thickness, global longitudinal strain, N-terminal prohormone of brain natriuretic peptide, and adverse cardiac outcomes compared with placebo at month 18, suggesting that patisiran may halt or reverse the progression of the cardiac manifestations of hATTR amyloidosis.. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01960348.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Double-Blind Method; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Patient Admission; Peptide Fragments; Prealbumin; Recovery of Function; RNA, Small Interfering; RNAi Therapeutics; Time Factors; Treatment Outcome; Ventricular Function, Left; Ventricular Remodeling; Young Adult

Myocardial fibrosis is characterized by excessive cross-linking and deposition of collagen type I and is involved in left ventricular stiffening and left ventricular diastolic dysfunction (LVDD). We investigated whether the effect of spironolactone on LVDD in patients with heart failure with preserved ejection fraction (HFpEF) depends on its effects on collagen cross-linking and/or deposition.. We investigated 381 HFpEF patients from the multicentre, randomized, placebo-controlled Aldo-DHF trial with measures of the E:e' ratio. The ratio of serum carboxy-terminal telopeptide of collagen type I to serum matrix metalloproteinase-1 (CITP:MMP-1, an inverse index of myocardial collagen cross-linking) and serum carboxy-terminal propeptide of procollagen type I (PICP, a direct index of myocardial collagen deposition) were determined at baseline and after 1-year treatment with spironolactone 25 mg once daily or placebo. Patients were classified by CITP:MMP-1 and PICP tertiles at baseline. While CITP:MMP-1 tertiles at baseline interacted (P < 0.05) with spironolactone effect on E:e', PICP tertiles did not. In fact, while spironolactone treatment did not modify E:e' in patients with lower CITP:MMP-1 levels, this ratio was significantly reduced in the remaining spironolactone-treated patients. In addition, PICP was unchanged in patients with lower CITP:MMP-1 levels but was reduced in the remaining spironolactone-treated patients.. A biochemical phenotype of high collagen cross-linking identifies HFpEF patients resistant to the beneficial effects of spironolactone on LVDD. It is suggested that excessive collagen cross-linking, which stabilizes collagen type I fibres, diminishes the ability of spironolactone to reduce collagen deposition in these patients.

Topics: Aged; Biomarkers; Cardiomyopathies; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Fibrosis; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Male; Mineralocorticoid Receptor Antagonists; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Prospective Studies; Spironolactone; Stroke Volume

The effect of combined cytokine and cell therapy in ischaemic cardiomyopathy is unknown. Meta-analyses suggest improved cardiac function with cell therapy. The optimal cell delivery route remains unclear. We investigated whether granulocyte colony-stimulating factor (G-CSF) alone or in combination with intracoronary (i.c.) or intramyocardial (i.m.) injection of autologous bone marrow-derived cells (BMCs) improves cardiac function.. Ninety patients with symptomatic ischaemic cardiomyopathy and no further treatment options were enrolled in the randomized, placebo-controlled, single-centre REGENERATE-IHD study. Randomization was to one of three arms: peripheral, i.c., or i.m. In each arm, patients were randomized to active treatment or placebo. All patients, apart from the peripheral placebo group (saline only) received G-CSF for 5 days. The i.c. and i.m. arms received either BMCs or serum (placebo). The primary endpoint was change in LVEF at 1 year assessed by cardiac magnetic resonance imaging/computed tomography. The i.m. BMC group showed a significant improvement in LVEF of 4.99% (95% confidence interval 0.33-9.6%; P = 0.038) at 1 year. This group also showed a reduction in NYHA class at 1 year and NT-proBNP at 6 months. No other group showed a significant change in LVEF. This finding is supported by post-hoc between-group comparisons.. We have shown that G-CSF combined with autologous i.m. BMCs has a beneficial effect on cardiac function and symptoms. However, this result should be considered preliminary in support of a clinical benefit of i.m. stem cell infusion in 'no option' patients and needs further exploration in a larger study.

Topics: Aged; Bone Marrow Transplantation; Cardiomyopathies; Coronary Vessels; Female; Granulocyte Colony-Stimulating Factor; Humans; Injections, Intra-Arterial; Injections, Intramuscular; Magnetic Resonance Imaging; Male; Middle Aged; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Stem Cell Transplantation; Stroke Volume; Tomography, X-Ray Computed; Transplantation, Autologous; United Kingdom

Topics: Aged; Aged, 80 and over; Amyloid; Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Doxycycline; Drug Administration Schedule; Drug Therapy, Combination; Female; Gene Expression; Humans; Male; Middle Aged; Mutation; Natriuretic Peptide, Brain; Patient Dropouts; Peptide Fragments; Prealbumin; Prospective Studies; Survival Analysis; Treatment Failure; Ursodeoxycholic Acid

The uptake of bone-seeking radiotracers in the amyloid heart is well recognised. 99. Patients diagnosed with AL and ATTR (wild-type and inherited) cardiac amyloidosis were prospectively recruited from the Princess Alexandra Hospital Amyloidosis Centre. Patients underwent injection with. 99

Topics: Aged; Amyloid Neuropathies, Familial; Australia; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Organotechnetium Compounds; Sulfur Compounds; Tomography, Emission-Computed; Troponin I

Carvedilol has established its evidence to improve prognosis and facilitate left ventricular reverse remodeling (LVRR) in heart failure patients with reduced left ventricular ejection fraction (LVEF), and many studies have supported its dose-dependency. However, there are few studies demonstrating the effect of high dose carvedilol in Japan. We enrolled 23 patients with idiopathic non-ischemic cardiomyopathy, in whom LVEF remained 45% or less despite 20 mg/ day of carvedilol therapy for > 3 months. After high dose (40 mg/day) carvedilol therapy for > 3 months, LVEF improved (+9.1%, P = 0.002), and LV end-diastolic diameter (LVDd) and LV end-systolic diameter (LVDs) reduced (-4.6 and -6.9 mm, respectively, P < 0.05) compared with the baseline data. Finally, 17 patients achieved LVRR after the high dose, when LVRR was defined as 1) those with final EF > 45%, and 2) those with final EF < 45% but who attained increases in LVEF > 10%, or LVEF > 5% with a decrease in LV end-diastolic dimension index (LVDDI) > 5%. Baseline predictors for LVRR after high dose carvedilol were the change rates of log B-type natriuretic peptide (BNP), LVDd, and LVDs from the time of pre-carvedilol introduction to enrollment (P < 0.05, respectively). In conclusion, high dose carvedilol triggered additional LVRR in patients with idiopathic non-ischemic cardiomyopathy and the change rates of log BNP, LVDd, and LVDs at 20 mg carvedilol may be predictors for the additional LVRR at high dose.

Topics: Adrenergic beta-Antagonists; Adult; Blood Pressure; Carbazoles; Cardiomyopathies; Carvedilol; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Propanolamines; Stroke Volume; Ventricular Function, Left; Ventricular Remodeling

The role that plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponins T (cTnT) and I (cTnI) play in supplementing imaging to screen for cardiac late effects remains controversial and the impact of high-sensitivity cTnT and troponin-specific autoantibodies (cTnAAbs) remains unexplored. We studied the role of cardiac biomarkers as indicators of the late effects of anthracyclines among childhood cancer survivors.. We measured NT-proBNP, cTnT, high-sensitivity cTnT, cTnI and cTnAAbs in 76 childhood cancer survivors at a median of 9 years after primary diagnosis. The survivors underwent conventional and real-time three-dimensional echocardiography and 62 underwent cardiac magnetic resonance imaging (MRI).. Of the survivors, four (5.3%) without risk factors for cardiotoxicity were cTnAAb-positive with an impaired cardiac function in MRI. Another four (5.3%) had an abnormal NT-proBNP level associated with an abnormal cardiac function and risk factors for cardiotoxicity. None showed measurable cardiac troponins, determined by the three different methods, with even the high-sensitivity cTnT-levels remaining normal.. Elevated plasma NT-proBNP or cTnAAbs indicated that childhood cancer survivors benefitted from being evaluated with modern imaging, despite normal function in conventional echocardiography. However, troponins did not seem to provide additional information on the late cardiotoxicity of anthracyclines.

Topics: Adolescent; Anthracyclines; Antibiotics, Antineoplastic; Autoantibodies; Biomarkers; Cardiomyopathies; Child; Cross-Sectional Studies; Echocardiography; Female; Heart; Humans; Magnetic Resonance Imaging; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prospective Studies; Sensitivity and Specificity; Survivors; Troponin I; Troponin T; Young Adult

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Amylases; Biomarkers; C-Reactive Protein; Cardiomyopathies; Creatine Kinase; Diagnosis, Differential; Female; Humans; Lipase; Male; Middle Aged; Natriuretic Peptide, Brain; Pancreatitis; Peptide Fragments; Prospective Studies; Severity of Illness Index; Time Factors; Troponin T

We investigated the effects of transendocardial CD34(+) cell transplantation in patients with ischemic cardiomyopathy.. In a prospective crossover study, we enrolled 33 patients with ischemic cardiomyopathy with New York Heart Association class III and left ventricular ejection fraction <40%. In phase 1, patients were treated with medical therapy for 6 months. Thereafter, all patients underwent transendocardial CD34(+) cell transplantation. Peripheral blood CD34(+) cells were mobilized by granulocyte colony stimulating factor, collected via apheresis, and injected transendocardially in the areas of hibernating myocardium. Patients were followed up for 6 months after the procedure (phase 2). Two patients died during phase 1 and none during phase 2. The remaining 31 patients were 85% men, aged 57±6 years. In phase 1, we found no change in left ventricular ejection fraction (from 25.2±6.2% to 27.1±6.6%; P=0.23), N-terminal pro B-type natriuretic peptide (from 3322±3411 to 3672±5165 pg/mL; P=0.75) or 6-minute walk distance (from 373±68 to 411±116 m; P=0.17). In contrast, in phase 2 there was an improvement in left ventricular ejection fraction (from 27.1±6.6% to 34.9±10.9%; P=0.001), increase in 6-minute walk distance (from 411±116 to 496±113 m; P=0.001), and a decrease in N-terminal pro B-type natriuretic peptide (from 3672±5165 to 1488±1847 pg/mL; P=0.04). The average number of injected CD34(+) cells was 90.6±7.5×10(6). Higher doses of CD34(+) cells and a more diffuse distribution of transendocardial cell injections were associated with better clinical response.. Transendocardial CD34(+) cell transplantation may be associated with improved left ventricular function, decreased N-terminal pro B-type natriuretic peptide levels, and better exercise capacity in patients with ischemic cardiomyopathy. These effects seem to be particularly pronounced in patients receiving diffusely distributed cell injections and high-dose cell therapy.. http://www.clinicaltrials.gov. Unique identifier: NCT01350310.

Topics: Adult; Antigens, CD34; Blood Cells; Cardiomyopathies; Cross-Over Studies; Female; Follow-Up Studies; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Ischemia; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Recovery of Function; Treatment Outcome

Doxorubicin causes cardiac injury and cardiomyopathy in children with acute lymphoblastic leukemia (ALL). Measuring biomarkers during therapy might help individualize treatment by immediately identifying cardiac injury and cardiomyopathy.. Children with high-risk ALL were randomly assigned to receive doxorubicin alone (n = 100; 75 analyzed) or doxorubicin with dexrazoxane (n = 105; 81 analyzed). Echocardiograms and serial serum measurements of cardiac troponin T (cTnT; cardiac injury biomarker), N-terminal pro-brain natriuretic peptide (NT-proBNP; cardiomyopathy biomarker), and high-sensitivity C-reactive protein (hsCRP; inflammatory biomarker) were obtained before, during, and after treatment.. cTnT levels were increased in 12% of children in the doxorubicin group and in 13% of the doxorubicin-dexrazoxane group before treatment but in 47% and 13%, respectively, after treatment (P = .005). NT-proBNP levels were increased in 89% of children in the doxorubicin group and in 92% of children in the doxorubicin-dexrazoxane group before treatment but in only 48% and 20%, respectively, after treatment (P = .07). The percentage of children with increased hsCRP levels did not differ between groups at any time. In the first 90 days of treatment, detectable increases in cTnT were associated with abnormally reduced left ventricular (LV) mass and LV end-diastolic posterior wall thickness 4 years later (P < .01); increases in NT-proBNP were related to an abnormal LV thickness-to-dimension ratio, suggesting LV remodeling, 4 years later (P = .01). Increases in hsCRP were not associated with any echocardiographic variables.. cTnT and NT-proBNP may hold promise as biomarkers of cardiotoxicity in children with high-risk ALL. Definitive validation studies are required to fully establish their range of clinical utility.

Topics: Antibiotics, Antineoplastic; Biomarkers; C-Reactive Protein; Cardiomyopathies; Cardiotonic Agents; Child; Child, Preschool; Doxorubicin; Echocardiography; Female; Heart; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Razoxane; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; Troponin T; Ventricular Function, Left; Ventricular Remodeling

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers; Cardiomyopathies; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Heart; Humans; Male; Middle Aged; Mitoxantrone; Monitoring, Physiologic; Multiple Sclerosis; Natriuretic Peptide, Brain; Predictive Value of Tests

In thalassemia major (TM), severe cardiac siderosis can be treated by continuous parenteral deferoxamine, but poor compliance, complications and deaths occur. Combined chelation therapy with deferiprone and deferoxamine is effective for moderate myocardial siderosis, but has not been prospectively examined in severe myocardial siderosis.. T2* cardiovascular magnetic resonance (CMR) was performed in 167 TM patients receiving standard subcutaneous deferoxamine monotherapy, and 22 had severe myocardial siderosis (T2* < 8 ms) with impaired left ventricular (LV) function. Fifteen of these patients received combination therapy with subcutaneous deferoxamine and oral deferiprone with CMR follow-up.. At baseline, deferoxamine was prescribed at 38 +/- 10.2 mg/kg for 5.3 days/week, and deferiprone at 73.9 +/- 4.0 mg/kg/day. All patients continued both deferiprone and deferoxamine for 12 months. There were no deaths or new cardiovascular complications. The myocardial T2* improved (5.7 +/- 0.98 ms to 7.9 +/- 2.47 ms; p = 0.010), with concomitant improvement in LV ejection fraction (51.2 +/- 10.9% to 65.6 +/- 6.7%; p < 0.001). Serum ferritin improved from 2057 (CV 7.6%) to 666 (CV 13.2%) microg/L (p < 0.001), and liver iron improved (liver T2*: 3.7 +/- 2.9 ms to 10.8 +/- 7.3 ms; p = 0.006).. In patients with severe myocardial siderosis and impaired LV function, combined chelation therapy with subcutaneous deferoxamine and oral deferiprone reduces myocardial iron and improves cardiac function. This treatment is considerably less onerous for the patient than conventional high dose continuous subcutaneous or intravenous deferoxamine monotherapy, and may be considered as an alternative. Very prolonged tailored treatment with iron chelation is necessary to clear myocardial iron, and alterations in chelation must be guided by repeated myocardial T2* scans.. This trial is registered as NCT00103753.

Topics: Administration, Oral; Adult; beta-Thalassemia; Cardiomyopathies; Deferiprone; Deferoxamine; Drug Therapy, Combination; Female; Ferritins; Humans; Injections, Subcutaneous; Iron; Iron Chelating Agents; Italy; Liver; Magnetic Resonance Imaging; Male; Myocardium; Natriuretic Peptide, Brain; Prospective Studies; Pyridones; Severity of Illness Index; Siderosis; Stroke Volume; Treatment Outcome; Ventricular Dysfunction, Left

We tested the hypothesis that renin-angiotensin system inhibition could reverse left ventricular diastolic dysfunction in patients with type 2 diabetes.. Forty asymptomatic patients with type 2 diabetes were recruited in this double-blind cross-over trial. Left ventricular diastolic function was assessed at baseline with Doppler echocardiography; ratios of early to late peak flow velocity through the mitral orifice (E/A) and velocity time integral of early to late transmitral diastolic flow (VTIE/VTIA) were evaluated. In addition, plasma brain natriuretic peptide (BNP) was measured. Patients received randomly either ramipril (2.5 mg/day), or telmisartan (40 mg/day) or their combination for 3 months. Subsequently, every patient was crossed over to alternative regimens after a 2-week washout period. Measurements were repeated at the end of each treatment period. Both E/A and VTIE/VTIA ratios were increased (29 and 20% with ramipril, 25 and 23% with telmisartan and 36 and 28% with combination treatment, respectively, p < 0.001), whereas plasma BNP levels were significantly reduced with all 3 regimens (9% with ramipril, 25% with telmisartan and 36% with combination, p < 0.001).. Both ramipril and telmisartan improve echocardiographic left ventricular diastolic indices and reduce plasma BNP levels in diabetic patients; their combination yields an even better therapeutic effect.

Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Benzoates; Blood Flow Velocity; Cardiomyopathies; Cross-Over Studies; Diabetes Complications; Double-Blind Method; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Ramipril; Statistics, Nonparametric; Telmisartan; Treatment Outcome

Levosimendan is a novel inodilator that improves central haemodynamics and symptoms of patients with decompensated chronic heart failure. The role, however, of repeated levosimendan infusions in the management of these patients has not yet been properly assessed.. This randomised placebo-controlled trial investigated the effects of serial levosimendan infusions on cardiac geometry and function, and on biomarkers of myocardial injury and neurohormonal and immune activation (troponin T, N-terminal B-type natriuretic pro-peptide (NT-proBNP), C reactive protein (CRP) and interleukin (IL) 6) in patients with advanced heart failure.. 25 patients with decompensated chronic heart failure were randomised (2:1) to receive five serial 24-h infusions (every 3 weeks) of either levosimendan (n = 17) or placebo (n = 8), and were evaluated echocardiographically and biochemically before and after each drug infusion and 30 days after the final infusion.. Following treatment, cardiac end-systolic and end-diastolic dimension and volume indices were significantly reduced only in the levosimendan-treated patients (p<0.01). A significant decrease in NT-proBNP (p<0.01), high-sensitivity CRP (p<0.01) and plasma IL6 (p = 0.05) was also observed in the levosimendan group, whereas these markers remained unchanged in the placebo group; similar changes were observed after each drug infusion. Although the number of patients with a positive troponin T (>or=0.01 ng/ml) was not different between the two groups at baseline, it was significantly higher in the placebo-treated group during the final evaluation (p<0.05).. Serial levosimendan treatments improved left ventricular performance and modulated neurohormonal and immune activation beneficially in patients with advanced heart failure, without increasing myocardial injury.

Topics: Aged; Cardiomyopathies; Cardiotonic Agents; Cytokines; Electrocardiography; Female; Heart Failure; Humans; Hydrazones; Immunity, Cellular; Infusions, Intravenous; Male; Natriuretic Peptide, Brain; Peptide Fragments; Pyridazines; Simendan; Treatment Outcome; Troponin T; Vasodilator Agents; Ventricular Dysfunction, Left

To investigate N-terminal pro-brain natriuretic peptide (NT-proBNP) level as a prognostic factor and a marker of myocardial dysfunction in patients with septic shock.. Prospective observational study.. Intensive care unit.. A total of 39 patients diagnosed with septic shock and requiring mechanical ventilation.. Demographic, hemodynamic, respiratory, and biological data (notably NT-proBNP, lactate, and cardiac troponin I) were collected at inclusion and every 12 hrs. The independent factors for death were higher Sequential Organ Failure Assessment score in the 24-hr period after inclusion (odds ratio, 4.7; 95% confidence interval, 1.15-19.3) and the highest NT-proBNP level in the 24-hr period after inclusion (odds ratio, 1.12 per 1000 pg/mL increase; 95% confidence interval, 1.05-1.26). An NT-proBNP of >13,600 pg/mL predicted intensive care unit mortality with an accuracy of 77%. Area under the receiver operating characteristic curve was 0.8 (p = .002; 95% confidence interval, 0.66-0.93). NT-proBNP levels were over the accepted normal range in all patients. Values were highest between 24 and 36 hrs after onset of septic shock and were significantly higher in nonsurvivors at each time between inclusion and day 7. The lowest left ventricular stroke work index of the first 24-hr period after inclusion was the only factor that independently influenced higher NT-proBNP levels at the same time (odds ratio, 0.91; 95% confidence interval, 0.84-0.98).. NT-proBNP seems to be an early factor of prognosis and myocardial dysfunction in patients with septic shock.

Topics: Aged; Blood Pressure; Cardiomyopathies; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis; Prospective Studies; Respiration, Artificial; ROC Curve; Shock, Septic; Troponin I

Brain natriuretic peptide (BNP) is a marker of ventricular dysfunction and can be used to assess prognosis in heart failure and after myocardial infarction. Heart involvement is the most important prognostic factor and causes death in almost all patients with light-chain amyloidosis (AL). We investigated the prognostic value of NT-proBNP and its utility in monitoring amyloid heart dysfunction.. NT-proBNP was quantified at diagnosis in 152 consecutive patients seen at the coordinating center of the Italian Amyloidosis Study Group (Pavia) from 1999 throughout 2001. Heart involvement was estimated on the basis of clinical signs, electrocardiography, and echocardiography. NT-proBNP concentrations differed in patients with (n=90, 59%) and without (n=62, 41%) heart involvement (median: 507.8 pmol/L versus 22.1 pmol/L, P=10(-7)). The best cutoff for heart involvement was at 152 pmol/L (sensitivity: 93.33%, specificity: 90.16%, accuracy: 92.05%) and distinguished two groups with different survival (P<0.001). The Cox multivariate model including NT-proBNP was better than models including echocardiographic and clinical signs of heart involvement. NT-proBNP appeared to be more sensitive than conventional echocardiographic parameters in detecting clinical improvement or worsening of amyloid cardiomyopathy during follow-up.. NT-proBNP appeared to be the most sensitive index of myocardial dysfunction and the most powerful prognostic determinant in AL amyloidosis. It adds prognostic information for newly diagnosed patients and can be useful in designing therapeutic strategies and monitoring response. NT-proBNP is a sensitive marker of heart toxicity caused by amyloidogenic light chains.

Topics: Adult; Aged; Amyloidosis; Biomarkers; Cardiomyopathies; Female; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; ROC Curve; Sensitivity and Specificity; Survival Analysis

Topics: Aged; Arrhythmias, Cardiac; Cardiomyopathies; Cardiotonic Agents; Dobutamine; Female; Heart Failure; Heart Rate; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Agents; Natriuretic Peptide, Brain; Prospective Studies; Treatment Outcome; Ventricular Premature Complexes

The purpose of this study was to evaluate whether or not cardiac sympathetic nerve activity, using (123)I-meta-iodobenzylguanidine ((123)I-MIBG) imaging, and cardiac natriuretic peptides (atrial and brain, ANP and BNP) were independent predictors of cardiac events, and, if so, which was the stronger predictor. Planar (123)I-MIBG images were obtained from 62 patients with heart disease. Plasma ANP and BNP levels, left ventricular ejection fraction (LVEF) by echocardiography, serum total cholesterol and triglyceride were measured. (123)I-MIBG was assessed as the heart-to-mediastinum (H/M) ratio of the delayed image and the washout rate (WoR) from the early to the delayed image. Patients were followed up for an average of 16.2 months, and 12 of 62 patients had cardiac events. Patients with events had significantly lower LVEF and H/M ratio compared with those without events. They had significantly higher WoR, ANP and BNP. By multivariate Cox proportional hazard analysis, (123)I-MIBG (H/M or WoR), ANP and BNP were independent predictors for cardiac events. Event-free survival using a Kaplan-Meier model, with a threshold value of 2.0 for H/M and 45% for WoR, showed that patients with H/M<2.0 and/or WoR>45% had a significantly poorer prognosis. These results suggest that (123)I-MIBG imaging and cardiac natriuretic peptides are useful tools for the evaluation of patients with heart disease, and that cardiac sympathetic nerve activity is a stronger predictor of cardiac events.

Topics: 3-Iodobenzylguanidine; Angina Pectoris; Atrial Natriuretic Factor; Cardiomyopathies; Chronic Disease; Female; Follow-Up Studies; Heart Diseases; Heart Valve Diseases; Humans; Male; Middle Aged; Multivariate Analysis; Myocardial Infarction; Natriuretic Peptide, Brain; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic

This study assessed the prognostic value of Iodine-123-metaiodobenzylguanidine (MIBG) imaging and of the plasma level of cardiac natriuretic peptides in patients with left ventricular dysfunction resulting from cardiomyopathy. Predictors of cardiac death or hospitalization related to progressive heart failure were examined in 171 patients with chronic heart failure (96 patients with idiopathic cardiomyopathy and 75 patients with ischemic cardiomyopathy). All patients underwent MIBG imaging at rest and other hemodynamic studies. During a mean (+/-SD) follow-up period of 27+/-11 months, 11 patients died from heart failure and 16 required hospitalization. High MIBG washout was an independent predictor of cardiac death (relative risk [RR] = 1.158, p<0.0001) whereas the plasma level of brain natriuretic peptide (BNP: relative risk [RR] = 1.005, p<0.0001) and high MIBG washout (relative risk [RR] = 1.094, p<0.0001) were predictors of progressive heart failure (ie, combined cardiac death and hospitalization). Accelerated myocardial adrenergic nerve activity as assessed by MIBG imaging and the plasma levels of BNP are powerful predictors of the patient's prognosis.

Topics: 3-Iodobenzylguanidine; Aged; Atrial Natriuretic Factor; Cardiomyopathies; Death; Disease-Free Survival; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Radionuclide Imaging; Radiopharmaceuticals; Regression Analysis; Treatment Outcome; Ventricular Dysfunction, Left

Adrenomedullin (AM) is a potent vasodilatory peptide discovered in human pheochromocytoma tissue. Proadrenomedullin N-terminal 20 peptide (PAMP) processed from an AM precursor is also a novel hypotensive peptide which inhibits catecholamine secretion from sympathetic nerve endings.. The present study sought to examine the relationships between the two peptides and other clinical parameters by measuring the plasma AM and PAMP concentrations in 98 patients with heart failure.. In all, 98 patients [65 men and 33 women, aged 58.2 +/- 11.0 years, mean +/- standard deviation (SD)] with heart failure and 26 healthy volunteers (12 men and 14 women, aged 54.1 +/- 8.6 years) were examined in this study. Heart failure was secondary to previous myocardial infarction in 58 patients, valvular disease in 28, cardiomyopathy in 9, and congenital heart disease in 3. All patients were classified into two groups of class I or II (Group 1) and class III or IV (Group 2) according to the New York Heart Association (NYHA) functional classification.. Both plasma AM and PAMP concentrations in the patients were significantly higher than those in healthy volunteers. In addition, plasma AM and PAMP concentrations in patients in class III or IV of New York Heart Association (NYHA) classification were significantly higher than those in NYHA class I or II. The elevated plasma concentrations of these peptides in patients in NYHA class III or IV significantly decreased in response to the treatment for 7 days. There was a significant correlation between plasma AM and PAMP, though the plasma concentration of PAMP was one-fifth to one-seventh of that of AM in patients and controls. The plasma AM concentration correlated significantly with the plasma concentrations of atrial and brain natriuretic peptides, epinephrine, and right atrial pressure, whereas such a relationship was not noted for the plasma PAMP concentration.. Judging from the difference in not only the biological actions but also the hormonal profiles between AM and PAMP, they may differentially modulate the cardiovascular system in patients with heart failure, although they are processed from the same precursor.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Cardiac Catheterization; Cardiomyopathies; Epinephrine; Female; Follow-Up Studies; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peptides; Prognosis; Proteins; Radioimmunoassay; Vasodilator Agents

Whether biomarkers may enable early identification of women who develop peripartum cardiomyopathy (PPCM) prior to disease onset remains a question of interest.. A retrospective nested case-control study was conducted to determine whether first trimester. First trimester NT-proBNP concentrations were numerically higher among women who subsequently developed PPCM (116 pg/mL [83-177]) as compared with women in control A (56.1 pg/mL [38.7-118.7],. There were differences in first trimester NT-proBNP and hs-cTnI concentrations between women who subsequently developed PPCM and those who did not, raising the possibility the early pregnancy subclinical myocardial dysfunction may be associated with this late-pregnancy disease.. · First trimester NT-proBNP is numerically higher among women who subsequently develop PPCM.. · First trimester hs-cTnI was nominally higher among women who developed PPCM versus those who did not.. · A significant proportion of normal pregnant women have undetectable hs-cTnI..

Topics: Biomarkers; Cardiomyopathies; Case-Control Studies; Female; Humans; Natriuretic Peptide, Brain; Peripartum Period; Pregnancy; Pregnancy Trimester, First; Retrospective Studies

Galectin-3, a biomarker of inflammation and fibrosis, can be associated with renal and myocardial damage and dysfunction in patients with acute heart failure (AHF).. We retrospectively analyzed 790 patients with AHF who were enrolled in the AKINESIS study. During hospitalization, patients with galectin-3 elevation (> 25.9 ng/mL) on admission more commonly had acute kidney injury (assessed by KDIGO criteria), renal tubular damage (peak urine neutrophil gelatinase-associated lipocalin [uNGAL] > 150 ng/dL) and myocardial injury (≥ 20% increase in the peak high-sensitivity cardiac troponin I [hs-cTnI] values compared to admission). They less commonly had ≥ 30% reduction in B-type natriuretic peptide from admission to last measured value. In multivariable linear regression analysis, galectin-3 was negatively associated with estimated glomerular filtration rate and positively associated with uNGAL and hs-cTnI. Higher galectin-3 was associated with renal replacement therapy, inotrope use and mortality during hospitalization. In univariable Cox regression analysis, higher galectin-3 was associated with increased risk for the composite of death or rehospitalization due to HF and death alone at 1 year. After multivariable adjustment, higher galectin-3 levels were associated only with death.. In patients with AHF, higher galectin-3 values were associated with renal dysfunction, renal tubular damage and myocardial injury, and they predicted worse outcomes.

Topics: Acute Disease; Acute Kidney Injury; Biomarkers; Cardiomyopathies; Galectin 3; Heart Failure; Humans; Kidney; Lipocalin-2; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Troponin I

Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data on longitudinal studies about early and late onset cardiotoxicity in this group of patients is scarce. The objective of the present study was to assess predictors of early and late onset cardiotoxicity in patients with breast cancer treated with A.. 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) to treat breast cancer were included in this prospective study. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years after the beginning of CHT. Clinical data, systolic and diastolic echo parameters and cardiac biomarkers including high sensitivity Troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Heart-type fatty acid binding protein (H-FABP) were assessed.. Mean doxorubicin dose was 243 mg/m2. Mean follow-up was 51.8 ± 8.2 months. At one-year incidence of anthracycline related-cardiotoxicity (AR-CT) was 4% and at the end of follow-up was 18% (15 patients asymptomatic left ventricular systolic dysfunction, 1 patients heart failure and 2 patients a sudden cardiac death). Forty-nine patients developed diastolic dysfunction (DD) during first year. In the univariate analysis DD during first year was the only parameter associated with AR-CT (Table 1). In the logistic regression model DD was independently related with the development of AR-CT, with an odds ratio value of 7.5 (95% CI 1.59-35.3).. Incidence of late-onset cardiotoxicity is high but mostly subclinical. Diastolic dysfunction early after chemotherapy is a strong predictor of anthracycline cardiotoxicity.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cardiotoxicity; Female; Humans; Incidence; Natriuretic Peptide, Brain; Prospective Studies

Two siblings presented with cardiomyopathy, hypertension, arrhythmia, and fibrosis of the left atrium. Each had a homozygous null variant in

Topics: Arrhythmias, Cardiac; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiomyopathies; Fibrosis; Heart Atria; Humans; Hypertension; Natriuretic Peptide, Brain; Serine Endopeptidases; Siblings

To analyze the association of circulating dehydroepiandrosterone sulfate (DHEA-S) levels with cardiovascular outcomes in patients with chronic Chagas cardiomyopathy (CCM) diagnosis.. DHEA-S is among the main endogenous steroid hormones. Some studies have suggested a relevant role of this hormone in infections and the setting of CCM. Nevertheless, no study has evaluated the prognostic role of DHEA-S in CCM patients.. Prospective cohort study. Patients with CCM and reduced ejection fraction were included. We explored the association of DHEA-S levels with NT-proBNP levels and echocardiographic variables using linear regression models. Next, by using Cox Proportional Hazard models, we examined whether levels of DHEA-S could predict a composite outcome (CO) including all-cause mortality, cardiac transplantation, and implantation of a left ventricular assist device (LVAD).. Seventy-four patients were included (59% males, median age: 64 years). After adjustment for confounding factors, high DHEA-S levels were associated with better LVEF, lower left atrium volume, end-systolic volume of the left ventricle and lower NT-proBNP levels. 43% of patients experienced the CO during a median follow-up of 40 months. Increased levels of DHEA-S were associated with a lower risk of developing the CO (HR 0.43; 95%CI 0.21-0.86). Finally, adding DHEA-S to the multivariate model did not improve the prediction of the CO, but substituting NT-proBNP in the model with DHEA-S showed similar performance.. In patients with CCM, higher DHEA-S levels were associated with lower mortality, heart transplantation, and LVAD implantation. Further larger studies are required to confirm our results and assess causality.

Topics: Biomarkers; Cardiomyopathies; Chagas Cardiomyopathy; Chagas Disease; Dehydroepiandrosterone; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Stroke Volume

To determine predictors of adverse outcomes in peripartum cardiomyopathy (PPCM).. We conducted a multi-center cohort study across four centers to identify subjects with PPCM with the following criteria: LVEF <40%, development of heart failure within the last month of pregnancy or within 5 months of delivery and no other identifiable cause of heart failure with reduced ejection fraction. Outcomes included 1) survival free from major adverse events (need for extra-corporeal membrane oxygenation, ventricular assist device, orthotopic heart transplantation or death) and 2) LVEF recovery ≥ 50%. Using a univariate logistic regression analysis, we identified significant clinical predictors of these outcomes, which were then used to create multivariable models. NT-proBNP at the time of diagnosis was examined both as a continuous variable (log transformed) in logistic regression and as a dichotomous variable (values above and below the median) using the log-rank test. In all, 237 women (1993 to 2017) with 736.4 person-years of follow-up, met criteria for PPCM. Participants had a mean age of 32.4 ± 6.7 years, mean BMI 30.6 ± 7.8 kg/m2; 63% were White. After median follow-up of 3.6 years (IQR 1.1-7.8), 113 (67%) had LVEF recovery, and 222 (94%) had survival free from adverse events. Significant predictors included gestational age, gravidity, systolic blood pressure, smoking, heart rate, initial LVEF, and diuretic use. In a subset of 110 patients with measured NTproBNP levels, we found a higher event free survival for women with NTproBNP <2585 pg/ml (median) as compared to women with NTproBNP ≥2585 pg/ml (log-rank test p-value 0.018).. Gestational age, gravidity, current or past tobacco use, systolic blood pressure, heart rate, initial LVEF and diuretic requirement at the time of diagnosis were associated with survival free from adverse events and LVEF recovery. Initial NT-proBNP was significantly associated with event free survival.

Topics: Adult; Cardiomyopathies; Cohort Studies; Diuretics; Female; Heart Failure; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Peripartum Period; Pregnancy; Progression-Free Survival; Puerperal Disorders; Recovery of Function; Stroke Volume; Ventricular Function, Left

New-onset atrial fibrillation (NOAF) after acute myocardial infarction (AMI) is common and independently correlated with poor prognosis. The purpose of this study is to explore whether atrial cardiomyopathy (ACM) markers improve NOAF risk assessment and contribute to therapy decision-making to improve prognosis.. We retrospectively analyzed 4713 patients with AMI without a documented history of atrial fibrillation (AF). We measured markers of ACM including P-wave terminal force in ECG lead V1 (PTFV1), Left atrial dimension (LAD), and B-type natriuretic peptide (BNP). Patients were stratified into tertiles of PTFV1, LAD, and BNP levels. Associations between markers and NOAF were evaluated using logistic regression analysis.. Overall, 222 (4.71%) patients had NOAF out of 4713 patients. The prevalence of NOAF increased gradually with PTFV1, LAD, and BNP tertiles. On multivariable regression analysis with potential confounders, elevated PTFV1, LAD, and BNP markers were significantly associated with an increased risk of NOAF. The addition of PTFV1, LAD, and BNP to the AF risk factors recommended by the 2020 ESC Guidelines significantly improved risk discrimination for NOAF.. Atrial cardiomyopathy markers including PTFV1, LAD, and BNP were strongly associated with NOAF after AMI. The prediction performance of the clinical model for NOAF was increased by the addition of these markers.

Topics: Atrial Fibrillation; Biomarkers; Cardiomyopathies; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Retrospective Studies; Risk Factors

We included 318 patients in the analysis (n = 86 patients +ATTR-CM; n = 232 patients -ATTR-CM). The median follow-up time was 20.1 months. During the study period, 67% of +ATTR-CM patients received tafamidis (median treatment duration, 17 months). The median H/CL ratio was 1.58 (interquartile range, 1.40-1.75). An H/CL ratio of more than 1.6 or less than 1.6 did not seem to have an impact on survival probability in +ATTR-CM patients (P = .30; hazard ratio, 0.65; 95% confidence interval, 0.31-1.41). Cardiac biomarkers were poorly correlated with H/CL (troponin T, R

Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diphosphates; Heart Failure; Humans; Natriuretic Peptide, Brain; Prealbumin; Retrospective Studies; Technetium Tc 99m Pyrophosphate; Troponin T

Background Plasma biomarkers may aid in the detection of anthracycline-related cardiomyopathy (ACMP). However, the currently available biomarkers have limited diagnostic value in long-term childhood cancer survivors. This study sought to identify diagnostic plasma biomarkers for ACMP in childhood cancer survivors. Methods and Results We measured 275 plasma proteins in 28 ACMP cases with left ventricular ejection fraction <45%, 29 anthracycline-treated controls with left ventricular ejection fraction ≥53% matched on sex, time after cancer, and anthracycline dose, and 29 patients with genetically determined dilated cardiomyopathy with left ventricular ejection fraction <45%. Multivariable linear regression was used to identify differentially expressed proteins. Elastic net model, including clinical characteristics, was used to assess discrimination of proteins diagnostic for ACMP. NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the inflammatory markers CCL19 (C-C motif chemokine ligands 19) and CCL20, PSPD (pulmonary surfactant protein-D), and PTN (pleiotrophin) were significantly upregulated in ACMP compared with controls. An elastic net model selected 45 proteins, including NT-proBNP, CCL19, CCL20 and PSPD, but not PTN, that discriminated ACMP cases from controls with an area under the receiver operating characteristic curve (AUC) of 0.78. This model was not superior to a model including NT-proBNP and clinical characteristics (AUC=0.75;

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cancer Survivors; Cardiomyopathies; Cardiomyopathy, Dilated; Case-Control Studies; Child; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Stroke Volume; Ventricular Function, Left

Recent studies have demonstrated that hyperglycemia is a major risk factor for the development and exacerbation of cardiovascular disease (CVD). However, the molecular mechanisms involved in diabetic cardiomyopathy (DCM) have not been fully elucidated. In this study, we focused on the underlying mechanism of DCM. Leptin receptor-deficient db/db mice were used to model a type 2 diabetes mellitus (T2DM) model in our study. WT mice and db/db mice received 4-phenylbutyric acid (4-PBA) (25 mg/kg/day) and saline by intraperitoneal injection every other day for 4 weeks. WT and db/db mice were given tail vein injections of 100 μL of rAAV9-Sh-MAPK10 and rAAV9-Sh-GFP at the age of 6-8 weeks. Echocardiography was performed to measure cardiac function, histological examinations were used to evaluate ventricular hypertrophy and fibrosis. Quantitative RT-qPCR was used to assess the mRNA expression of Jun N-terminal kinase 3 (JNK3, MAPK10), atrial natriuretic factor (ANF), brain natriuretic peptide (BNP), and collagen I and III. Immunoblotting was performed to measure the levels of cardiac hypertrophy-related proteins, fibrosis-related proteins, endoplasmic reticulum stress (ERS)-related proteins and apoptosis-related proteins. TUNEL staining was performed to examine cardiomyocyte apoptosis. In contrast to 12-week-old db/db mice, 16-week-old db/db mice showed the most severe myocardial dysfunction. The DCM induced by hyperglycemia was largely alleviated by 4-PBA (25 mg/kg/day, intraperitoneal injection). Similarly, tail vein injection of rAAV9-Sh-MAPK10 reversed the phenotype of the heart in db/db mice including cardiac hypertrophy and apoptosis in db/db mice. The mechanistic findings suggested that hyperglycemia initiated the ERS response through the negative regulation of sirtuin 1 (SIRT1), leading to the occurrence of myocardial dysfunction, and specific knockdown of MAPK10 in the heart directly reversed myocardial dysfunction induced by hyperglycemia. We demonstrated that hyperglycemia promotes DCM in db/db mice through the ERS-MAPK10 signaling pathway in diabetic mice.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Cardiomyopathies; Collagen; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Endoplasmic Reticulum Stress; Fibrosis; Hyperglycemia; JNK Mitogen-Activated Protein Kinases; Mice; Mitogen-Activated Protein Kinase 10; Natriuretic Peptide, Brain; Receptors, Leptin; RNA, Messenger; Signal Transduction; Sirtuin 1

Infection with human immunodeficiency virus (HIV) is associated with higher risk for myocardial disease despite modern combination antiretroviral therapy (cART). Factors contributing to this excess risk, however, remain poorly characterized. We aimed to assess cross-sectional relationships between elevations of left atrial volume index (LAVI) and myocardial extracellular volume (ECV) fraction that have been reported in persons living with HIV and levels of circulating biomarkers of inflammation, fibrosis, and myocyte stretch among persons living with and without HIV (PLWH, PLWOH).. Participants from three cohorts of PLWH and PLWOH underwent cardiovascular magnetic resonance imaging for measurement of LAVI and ECV. Levels of circulating proteins (IL-6, sCD14, galectin-3, NT-proBNP, GDF-15, TIMP-2, MMP-2, and hsTnI) were measured using immunoassays. Associations were assessed using logistic and linear regression, adjusting for demographics, substance use, and clinical characteristics.. Among 381 participants with and without HIV, median age (IQR) was 55.1 (51.2, 58.4) years, 28% were female, 69% were Black, and 46% were current smokers. Sixty-two percent were PLWH (n = 235), of whom 88% were receiving cART and 72% were virally suppressed. PLWH had higher levels of sCD14 (p = < 0.001), GDF-15 (p = < 0.001), and NT-proBNP (p = 0.03) compared to PLWOH, while levels of other biomarkers did not differ by HIV serostatus, including IL-6 (p = 0.84). Among PLWH, higher sCD14, GDF-15, and NT-proBNP were also associated with lower CD4 + cell count, and higher NT-proBNP was associated with detectable HIV viral load. NT-proBNP was associated with elevated LAVI (OR: 1.79 [95% CI: 1.31, 2.44]; p < 0.001) with no evidence of effect measure modification by HIV serostatus. Other associations between HIV-associated biomarkers and LAVI or ECV were small or imprecise.. Our findings suggest that elevated levels of sCD14, GDF-15, and NT-proBNP among PLWH compared to PLWOH observed in the current cART era may only minimally reflect HIV-associated elevations in LAVI and ECV. Future studies of excess risk of myocardial disease among contemporary cohorts of PLWH should investigate mechanisms other than those connoted by the studied biomarkers.

Topics: Biomarkers; Cardiomyopathies; Female; Growth Differentiation Factor 15; Heart Atria; HIV Infections; Humans; Interleukin-6; Lipopolysaccharide Receptors; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Although sacubitril/valsartan (Sac/Val) is indicated for the treatment of heart failure with reduced ejection fraction (HFrEF), gaps in care continue to exist for those with newer onset HFrEF vs those with longer durations of disease.. We categorized 794 persons with HFrEF (EF of ≤40%) according to a HF duration of less than 12 months, 12-24 months, 24-60 months, and more than> 60 months. After the initiation of Sac/Val, concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were measured, and Kansas City Cardiomyopathy Questionnaire 23 scores were obtained serially from baseline to 12 months. The left ventricular ejection fraction was measured by echocardiography. Significant decreases in the concentrations of N-terminal pro-B type natriuretic peptide, high sensitivity cardiac troponin T, and soluble ST2 were observed regardless of HF duration (P < .001). Comparable gains in Kansas City Cardiomyopathy Questionnaire 23 scores were achieved in all HF duration categories. Moreover, consistent reverse cardiac remodeling in all HF duration categories occurred, with the absolute left ventricular ejection fraction improvement by 12 months across HF duration groups of 12.2%, 6.9%, 8.5%, and 8.6% for HF duration of less than 12 months, 12-24 months, 24-60 months, and more than 60 months, respectively.. The initiation of Sac/Val decreases prognostic biomarkers, improves health status, and reverses cardiac remodeling processes, regardless of HF duration.. We categorized 794 persons with heart failure owing to a low ejection fraction according to disease duration into 4 groups: less than 12 months, 12-24 months, 24-60 months, and more than 60 months. After the initiation of sacubitril/valsartan (Entresto), we found that regardless of the duration of heart failure significant improvements occurred in cardiac biomarkers, patients felt better with improved health status and on testing with cardiac ultrasound examination, improvement in heart size, and function occurred. These results suggest that, regardless of heart failure duration, patients with a reduced ejection fraction would benefit from use of sacubitril/valsartan for their care.

Topics: Aminobutyrates; Angiotensin Receptor Antagonists; Biomarkers; Biphenyl Compounds; Cardiomyopathies; Drug Combinations; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Stroke Volume; Tetrazoles; Troponin T; Valsartan; Ventricular Function, Left; Ventricular Remodeling

Based on many previous studies, liver cirrhosis is traditionally associated with cardiac dysfunction. The main clinical features of cirrhotic cardiomyopathy include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities, and chronotropic incompetence. Previous studies have found that the levels of brain natriuretic peptide (BNP) and its precursor the N-terminal pro B-type natriuretic peptide (NT-proBNP) are elevated in cirrhosis with systolic as well as diastolic dysfunction.

Topics: Cardiomyopathies; Humans; Liver Cirrhosis; Natriuretic Peptide, Brain; Peptide Fragments

Both increased natriuretic peptide levels and restrictive filling pattern (RFP) are important risk predictors in patients with heart failure. The aim of this study was to examine the role of the combined use of natriuretic peptide and RFP for the prognostic stratification of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration in the Biomarker Plus study.. A total of 186 patients (aged 64 ± 10 years) underwent echocardiographic study and N-terminal pro-B-type natriuretic peptide assay at baseline (before surgical ventricular restoration). Patients were divided into 4 groups depending on baseline diastolic filling pattern (RFP/no RFP) and N-terminal pro-B-type natriuretic peptide level (less than or greater than or equal to the upper tertile value of 2003 ŋg/L). RFP was defined as E/A ratio ≥2. All-cause death or heart failure hospitalizations within 36-month follow-up were analyzed.. Despite similar ejection fraction, volumes, and mass, the 4 groups presented distinct clinical and structural pattern of presurgical ventricular restoration ventricular remodeling and significantly different clinical outcome after surgical unloading. During follow-up, 67 patients died or were hospitalized for heart failure (36%). High N-terminal pro-B-type natriuretic peptide levels and RFP, considered individually, were significantly associated with outcome (P < .0001). The combination of both was associated with the highest adjusted hazard of adverse events (hazard ratio, 3.63; 95% CI, 1.73-7.6; P < .0001).. The simultaneous use of 2 markers, 1 biological and 1 echocardiographic, may allow better prognostic stratification and characterization of the distinct structural and clinical phenotypes in a population of patients with ischemic cardiomyopathy undergoing surgical ventricular restoration. This approach could be useful in the decision-making process to guide treatment choices in patients with ischemic cardiomyopathy.

Topics: Biomarkers; Cardiomyopathies; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Ventricular Remodeling

Wild-type transthyretin amyloid cardiomyopathy (wtATTR-CM) is a progressive and fatal condition. Although prognosis can be determined at the time of diagnosis according to National Amyloidosis Centre (NAC) transthyretin amyloidosis (ATTR) stage, the clinical course varies substantially between individuals. There are currently no established measures of rate of disease progression. Through systematic analysis of functional, biochemical and echocardiographic disease-related variables we aimed to identify prognostic markers of disease progression in wtATTR-CM.. This is a retrospective observational study of 432 patients with wtATTR-CM diagnosed at the UK NAC, none of whom received disease-modifying therapy. The association between mortality from the 12-month timepoint and change from diagnosis to 12 months in a variety of disease-related variables was explored using Cox regression.. Change in N-terminal pro-B-type natriuretic peptide concentration (∆ NT-proBNP) at 12 months from diagnosis was the strongest predictor of ongoing mortality and was independent of both change in other disease-related variables (HR 1.04 per 500 ng/L increase (95% CI 1.01 to 1.07); p=0.003) and a range of known prognostic variables at the time of diagnosis (HR 1.07 per 500 ng/L increase (95% CI 1.02 to 1.13); p=0.007). An increase in NT-proBNP of >500 ng/L, >1000 ng/L and >2000 ng/L during the first year of follow-up occurred in 45%, 35% and 16% of patients, respectively.. Change in NT-proBNP concentration during the first year of follow-up is a powerful independent predictor of mortality in wtATTR-CM.

Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Disease Progression; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Prealbumin; Prognosis

To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer.. We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated.. There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279).. Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

Topics: Aged; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cardiotoxicity; Female; Humans; Intraoperative Care; Mastectomy, Segmental; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radiotherapy, Adjuvant; Troponin I

Survivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown.. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest-directed radiation therapy (RT). NT-proBNP values above age- and sex-specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross-sectional associations between abnormal NT-proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death.. At a median age of 35.5 years (interquartile range, 29.8-42.5 years), NT-proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose-dependent increased risk for abnormal NT-proBNP (P for trend <.0001). Among exposed survivors with no history of Common Terminology Criteria for Adverse Events-graded cardiomyopathy and with normal systolic function, survivors with abnormal NT-proBNP had higher rates per 1000 person-years of cardiac mortality (2.93 vs 0.96; P < .0001) and future cardiomyopathy (32.10 vs 15.98; P < .0001) and an increased risk of future cardiomyopathy (HR, 2.28; 95% CI, 1.28-4.08) according to a multivariable assessment.. Abnormal NT-proBNP values were prevalent and, among survivors who were exposed to cardiotoxic therapy but did not have a history of cardiomyopathy or current systolic dysfunction, identified those at increased risk for future cardiomyopathy. Further longitudinal studies are needed to confirm this novel finding.

Topics: Adult; Biomarkers; Cancer Survivors; Cardiomyopathies; Cardiotoxicity; Child; Cohort Studies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Troponin T; Young Adult

Geriatric patients with coronavirus disease (COVID-19) are at high risk of developing cardiac injury. Identifying the factors that affect high-sensitivity cardiac troponin I may indicate the cause of cardiac injury in elderly patients, and this could hopefully assist in protecting heart function in this patient population.. One hundred and eighty inpatients who were admitted for COVID-19 were screened. Patients older than 60 years were included in this study, and the clinical characteristics and laboratory results of the cohort were analyzed. The correlation between cardiac injury and clinical/laboratory variables was statistically analyzed, and further logistic regression was performed to determine how these variables influence cardiac injury in geriatric patients.. Age (p < 0.001) significantly correlated with cardiac injury, whereas sex (p = 0.372) and coexisting diseases did not. Rising procalcitonin (p = 0.001), interleukin-2 receptor (p < 0.001), interleukin 6 (p = 0.001), interleukin 10 (p < 0.001), tumor necrosis factor α (p = 0.001), high-sensitivity C-reactive protein (p = 0.001), D-dimer (p < 0.001), white blood cells (p < 0.001), neutrophils (p = 0.001), declining lymphocytes (p < 0.001), and natural killer cells (p = 0.005) were associated with cardiac injury and showed predictive ability in the multivariate logistic regression.. Our results suggest that age and inflammatory factors influence cardiac injury in elderly patients. Interfering with inflammation in this patient population may potentially confer cardiac protection.

Topics: Aged; Aged, 80 and over; Cardiomyopathies; COVID-19; Creatine Kinase; Humans; Inflammation Mediators; Killer Cells, Natural; L-Lactate Dehydrogenase; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Risk Factors; Troponin T

Timely recognition of cardiac amyloidosis is clinically important, but the diagnosis is frequently delayed.. We sought to identify a multi-modality approach with the highest diagnostic accuracy in patients evaluated by cardiac biopsy, the diagnostic gold standard.. Consecutive patients (N = 242) who underwent cardiac biopsy for suspected amyloidosis within an 18-year period were retrospectively identified. Cardiac biomarker, ECG, and echocardiography results were examined for correlation with biopsy-proven disease. A prediction model for cardiac amyloidosis was derived using multivariable logistic regression.. Among patients with an advanced infiltrative cardiomyopathy phenotype, traditional biomarker, ECG, and echocardiography-based screening tests have limited individual diagnostic utility for cardiac amyloidosis. A prediction algorithm including age, relative wall thickness, E/e', and low limb lead voltage improves the detection of cardiac biopsy-proven disease.

Topics: Age Factors; Aged; Amyloid Neuropathies, Familial; Amyloidosis; Biopsy; Blood Flow Velocity; Cardiomyopathies; Clinical Decision Rules; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Immunoglobulin Light-chain Amyloidosis; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Organ Size; Sex Factors; Troponin I

Myocardial involvement (MCI) is known to increase morbidity and mortality in polymyositis (PM) and dermatomyositis (DM). This study aims to investigate whether complicating with ventricular arrhythmia (VA) predicts poor outcomes in patients with PM/DM-related myocardial involvement (PM/DM-MCI).. We reviewed all PM/DM-MCI patients admitted to Peking Union Medical College Hospital from October 1997 to April 2019. VA and the other possible risk factors for the composite endpoint, including death from any cause and rehospitalization for cardiac causes, were analyzed.. A total of 75 PM/DM-MCI patients (44 PM and 31 DM) were enrolled, of which 27 (36%) met the composite endpoint during a median follow-up of 24 months. Independent prognostic factors for the composite endpoint include VA [HR 4.215, 95% CI (1.737, 10.230)], NT-proBNP > 3415 pg/ml [HR 2.606, 95% CI (1.203, 5.646)], interstitial lung disease [HR 2.688, 95% CI (1.209, 5.978)], and anti-cardiac remodelling therapy [HR 0.302, 95% CI (0.115, 0.792)]. The 3-year event-free survival rate of patients without VA was significantly higher than that of patients with VA (63.3% vs 40.7%, P = 0.034). Skin lesions [OR 0.163, 95% CI (0.051, 0.523)] and positive antimitochondrial antibody [OR 3.484, 95% CI (1.192, 10.183)] were independent predictors of VA.. VA provides prognostic insights for PM/DM-MCI patients and predicts poor outcome. Polymyositis and positive antimitochondrial antibody are closely associated with the presence of VA in PM/DM-MCI.

Topics: Adrenergic beta-Antagonists; Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Arrhythmias, Cardiac; Autoantibodies; Cardiomyopathies; Dermatomyositis; Female; Humans; Lung Diseases, Interstitial; Male; Middle Aged; Mineralocorticoid Receptor Antagonists; Mitochondria; Natriuretic Peptide, Brain; Peptide Fragments; Polymyositis; Prognosis; Progression-Free Survival; Proportional Hazards Models; Retrospective Studies; Spironolactone; Survival Rate

Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis with poor prognosis. Currently, the predictors of cardiac involvement and prognostic staging systems are primarily based on conventional echocardiography and serological biomarkers. We used three-dimensional speckle tracking echocardiography (STE-3D) measurements of strain, hypothesizing that it could detect cardiac involvement and aid in prediction of mortality.. We retrospectively analysed 74 consecutive patients with biopsy-proven AL amyloidosis. Among them, 42 showed possible cardiac involvement and 32 without cardiac involvement. LV global longitudinal strain (GLS), global radial strain, global circumferential strain and global area strain (GAS) measurements were obtained.. The GLS and GAS were considered significant predictors of cardiac involvement. The cut-off values discriminating cardiac involvement were 16.10% for GLS, 32.95% for GAS. During the median follow-up of 12.5 months (interquartile range 4-25 months), 20 (27%) patients died. For the Cox proportional model survival analysis, heart rate, cardiac troponin T, NT-proBNP levels, E/e', GLS, and GAS were univariate predictors of death. Multivariate Cox model showed that GLS ≤ 14.78% and cardiac troponin T ≥ 0.049 mg/l levels were independent predictors of survival.. STE-3D measurements of LV myocardial mechanics could detect cardiac involvement in patients with AL amyloidosis; GLS and cardiac biomarkers can provided prognostic information for mortality prediction.

Topics: Aged; Biomarkers; Cardiomyopathies; Disease Progression; Echocardiography, Three-Dimensional; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; Time Factors; Troponin T; Ventricular Function, Left

Ventricular thrombus is an uncommon, severe condition with high morbidity and mortality. Simultaneous left and right ventricular thrombi caused by lupus myocardiopathy have not been previously reported in the literature. This case presents a 42-year-old woman who has bilateral ventricular thrombi with reduced left ventricular ejection fraction (35.4%) and acute kidney injury. Pro-brain natriuretic peptide was >35000 pg/mL. Systemic lupus erythematosus was confirmed based on multiorgan injuries including malar rash, anemia, renal injury, positive antinuclear, anti-Smith antibodies, and decreased complements. Renal biopsy revealed lupus nephritis class III + V. Low molecular weight heparin, steroids, and mycophenolate mofetil were initiated, after which the patient experienced transient numbness in the right limbs and hemoptysis. She then recovered quickly and improved significantly with recovery of left ventricular systolic function (left ventricular ejection fraction 46%) and the eventual disappearance of thrombi. Simultaneous left and right ventricular thrombi are rare but life-threatening condition, prompting consideration of myocardiopathy caused by autoimmune diseases such as lupus. Timely treatment with immunosuppressants and anticoagulants may resolve the thrombi and improve cardiac function.

Topics: Acute Kidney Injury; Adult; Anticoagulants; Biopsy; Cardiomyopathies; Drug Therapy, Combination; Female; Heart Ventricles; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Lupus Nephritis; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Thrombosis; Treatment Outcome; Ventricular Dysfunction, Left

Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure worldwide. Although a significant number of women recover their left ventricular (LV) function within 12 months, some remain with persistently reduced systolic function.. Knowledge gaps exist on predictors of myocardial recovery in PPCM. N-terminal pro-brain natriuretic peptide (NT-proBNP) is the only clinically established biomarker with diagnostic value in PPCM. We aimed to establish whether NT-proBNP could serve as a predictor of LV recovery in PPCM, as measured by LV end-diastolic volume (LVEDD) and LV ejection fraction (LVEF).. This study of 35 women with PPCM (mean age 30.0 ± 5.9 years) had a median NT-proBNP of 834.7 pg/ml (IQR 571.2-1840.5) at baseline. Within the first year of follow-up, 51.4% of the cohort recovered their LV dimensions (LVEDD < 55 mm) and systolic function (LVEF > 50%). Women without LV recovery presented with higher NT-proBNP at baseline. Multivariable regression analyses demonstrated that NT-proBNP of ≥ 900 pg/ml at the time of diagnosis was predictive of failure to recover LVEDD (OR 0.22, 95% CI 0.05-0.95, P = 0.043) or LVEF (OR 0.20 [95% CI 0.04-0.89], p = 0.035) at follow-up.. We have demonstrated that NT-proBNP has a prognostic value in predicting LV recovery of patients with PPCM. Patients with NT-proBNP of ≥ 900 pg/ml were less likely to show any improvement in LVEF or LVEDD. Our findings have implications for clinical practice as patients with higher NT-proBNP might require more aggressive therapy and more intensive follow-up. Point-of-care NT-proBNP for diagnosis and risk stratification warrants further investigation.

Topics: Adult; Biomarkers; Cardiomyopathies; Diastole; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Peripartum Period; Predictive Value of Tests; Pregnancy; Prognosis; Stroke Volume; Systole

Biomarkers reflecting myocardial fibrosis and inflammation have been individually associated with left ventricular hypertrophy (LVH) and diastolic dysfunction (DD). However, the added value of a fibrosis-inflammation multimarker approach in a populational setting is yet to be studied. We evaluated the value of a multimarker approach to detect LVH and DD in a large population-based cohort.. As the measurement of Gal3, P3NP, and ST2 results in marginal (even if significant) increase in the prediction of DD/LVH on top of routine evaluation, their systematic use should not be promoted in unselected healthy individuals to screen for preclinical DD. Further research is needed to determine whether a more personalized medicine approach combing proteomic and clinical scoring can amplify the added value of biomarkers to identify preclinical DD.

Topics: Cardiomyopathies; Female; Humans; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Proteomics; Ventricular Remodeling

Topics: Atrioventricular Block; Biopsy; Cardiomyopathies; Diagnosis, Differential; Disease Progression; Echocardiography; Fluorodeoxyglucose F18; Giant Cells; Granuloma; Heart Block; Heart Failure; Heart Transplantation; Humans; Lymph Nodes; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Positron Emission Tomography Computed Tomography; Radiopharmaceuticals; Sarcoidosis; Stroke Volume; Troponin I

Cardiac involvement and dysfunction are common in patients presenting with AL and ATTR Amyloidosis. Cardiopulmonary exercise testing (CPET) performance is the gold standard to quantify functional capacity.. In this study, we evaluated CPET measurements in 41 patients with cardiac Amyloidosis and their correlation with current amyloid specific staging criteria.. In both AL and ATTR cardiac Amyloidosis, percent predicted peak VO2 is significantly reduced and correlates with biomarker abnormalities. The association of cardiac biomarkers with peak VO2 is stronger for AL Amyloidosis (NT-proBNP (r = -0.57, P=0.006), Troponin (r = -0.70, p < 0.001) than ATTR (NT-proBNP (r = -0.4, P = 0.04) and Troponin (r = -0.57, P = 0.002) despite lower left ventricular mass in the former, suggesting that this may be further evidence for light chain toxicity in AL amyloidosis.. Our findings suggest further evidence for AL toxicity.

Topics: Aged; Amyloidosis; Biomarkers; Cardiomyopathies; Exercise Test; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Prognosis; Survival Analysis; Troponin

The study aimed to investigate whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration and/or left atrial volume index (LAVI), as atrial cardiopathy biomarkers, were associated with infarct patterns on diffusion-weighted imaging in patients with embolic strokes of undetermined source (ESUS).. We retrospectively evaluated patient with ESUS from our stroke registry between January 2018 and November 2019. Cut-off values for atrial cardiopathy biomarkers were defined as >250 pg/mL for NT-proBNP and >34 mL/m. Among 194 eligible patients with ESUS (76 women; mean age, 69.2 years), simultaneous increases of NT-proBNP concentration and LAVI were identified in 39 (20.1%). Group 3 had a significantly larger infarct volume, relative to Group 1 and Group 2 (P=0.043) Multivariable logistic regression analyses revealed that these patients (Group 3) were significantly more likely to have multi-territorial infarcts (adjusted odds ratio [aOR]: 3.03, 95% confidence interval [CI]: 1.05-8.72; P=0.04), a maximal lesion diameter >15mm (aOR: 4.51, 95% CI: 1.70-11.93; P=0.001), and large cortical infarctions (aOR: 4.17, 95% CI: 1.75-9.96; P=0.001).. We found that simultaneously increased values for NT-proBNP concentration and LAVI were independently associated with multi-territorial and large cortical infarct patterns in patients with ESUS. These findings suggest that NT-proBNP and LAVI may be useful biomarkers for identifying cardioembolic subtypes and guiding treatment selection in patients with ESUS.

Topics: Aged; Aged, 80 and over; Atrial Function, Left; Atrial Remodeling; Biomarkers; Brain Infarction; Cardiomyopathies; Diffusion Magnetic Resonance Imaging; Echocardiography; Embolic Stroke; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Registries; Retrospective Studies; Time Factors

Light chain (AL) cardiac amyloidosis is associated with a poor prognosis. Diagnosing at an early stage is critical for treatment and the management of cardiac complication.. We aimed to evaluate the diagnostic performance of

Topics: Adult; Aged; Aprotinin; Biopsy; Cardiomyopathies; Defibrillators, Implantable; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Organotechnetium Compounds; Peptide Fragments; Prospective Studies; Single Photon Emission Computed Tomography Computed Tomography

The clinical significance of left ventricular (LV) trabeculation remains unknown in cardiomyopathies. B-Type natriuretic peptide (BNP) strongly reflects LV end-diastolic wall stress and is a useful prognostic marker of cardiovascular diseases. The enhanced identification of LV trabeculae (T) with the use of cardiac magnetic resonance and the evaluation of its relationship with BNP may elucidate the biologic significance and clinical impact of trabeculation in patients with nonischemic cardiomyopathy (NICM).. The LV volume and mass of 515 patients with NICM and 36 control subjects were analyzed with the use of a steady-state free precession sequence, and individual T mass was planimetred. Major adverse cardiac events (MACE) were assessed.. T mass index correlated with LV end-diastolic volume index (EDVI), LV mass index, and papillary muscle mass index (all P < 0.001). Also, T mass index was positively correlated with BNP level (R = 0.381; P < 0.001) and was an independent determinant of BNP after adjusting for age, sex, body mass index (BMI), etiology, LV ejection fraction, and LV EDVI (P < 0.001). Kaplan-Meier analysis during a median follow-up of 17.3 months showed that higher T mass index and increased BNP level correlated with MACE. On multivariate analysis, T mass index (P = 0.031) and BNP (P < 0.001) remained associated with poor outcomes when combined with age, sex, BMI, and etiology.. Increased LV trabeculation was associated with LV dysfunction/remodelling and impaired outcomes in NICM of various etiologies. This may support the biologic significance of LV trabeculation and could be attributed to its association with BNP through LV wall stress.

Topics: Aged; Cardiomyopathies; Female; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Organ Size; Retrospective Studies

Topics: Cardiomyopathies; Heart Ventricles; Humans; Natriuretic Peptide, Brain

The prognosis of cardiac light-chain (AL) amyloidosis is considered to be very poor. We studied the treatment efficacy and outcomes by retrospectively analyzing the clinical results of 45 patients with cardiac AL amyloidosis treated at our hospital between September 2008 and March 2016. The group of patients analyzed included 29 males and 16 females with a median age of 68 years. Their baseline median NT-proBNP, cTnT, and dFLC were 3167 pg/ml, 0.080 ng/ml, and 286.17 mg/l, respectively. Twenty-eight patients were in Cardiac Stage (CS) III and 17 patients were in Revised Prognostic Stage (RPS) IV. At the median follow-up of 10 months, the median overall survival (OS) was 16 months and 3-year OS was 35.9%. The patients in CS III showed significantly poorer survival rate than those in CS I or II (3-year OS: 12.2% vs. 65.8%, p = 0.0115) and the patients in RPS IV showed significantly poorer survival rate than those in RPS I, II, or III (3-year OS: 11.0% vs. 53.3%, p = 0.000914). Regardless of the therapeutic approaches, patients who achieved hematological CR or cardiac organ response demonstrated significantly improved prognosis. Therefore, achievement of hematological and organ responses is important in the treatment of cardiac AL amyloidosis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Bortezomib; Cardiomyopathies; Cyclophosphamide; Dexamethasone; Drug Therapy, Combination; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Japan; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Blood Stem Cell Transplantation; Prognosis; Retrospective Studies; Retroviridae Proteins, Oncogenic; Severity of Illness Index

Studies on the efficacy of implantable cardioverter-defibrillator (ICD) therapy for primary prevention in Asian patients are relatively lacking compared to those for secondary prevention. Also, it is important to stratify which patients will benefit from ICD therapy for primary prevention.. Of 483 consecutive patients who received new implantation of ICD in 9 centers in Korea, 305 patients with reduced left ventricular systolic function and/or documented ventricular fibrillation/tachycardia were enrolled and divided into primary (n = 167) and secondary prevention groups (n = 138).. During mean follow-up duration of 2.6 ± 1.6 years, appropriate ICD therapy occurred in 78 patients (25.6%), and appropriate ICD shock and anti-tachycardia pacing occurred in 15.1% and 15.1% of patients, respectively. Appropriate ICD shock rate was not different between the two groups (primary 12% vs. secondary 18.8%,. In this multicenter regional registry, the frequency of appropriate ICD therapy is not low in the primary prevention group. In addition, combination of poor prognostic factors of heart failure is useful in risk stratification of patients who are not benefiting from ICD therapy for primary prevention.

Topics: Aged; Cardiomyopathies; Death, Sudden, Cardiac; Defibrillators, Implantable; Electrocardiography; Female; Follow-Up Studies; Heart Ventricles; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Primary Prevention; Proportional Hazards Models; Registries; Republic of Korea; Risk Factors; Treatment Outcome; Ventricular Dysfunction, Left

The severity of heart disease varies widely among patients with transthyretin-related cardiac amyloidosis (ATTR-CA) at presentation, and availability of tools able to predict prognosis is essential for clinical and research purposes. Currently, two biomarker-based staging systems are available. The aim of this study was to compare their predictive performance.. A total of 175 patients diagnosed with ATTR-CA (133 wild-type and 42 hereditary) were stratified into different stages based on 2 systems: the first system included N-terminal pro-B-type natriuretic peptide (NT-proBNP) and estimated glomerular filtration rate (eGFR), and the second one included NT-proBNP and troponin I (TnI). Survival estimates and age-adjusted survival for all-cause mortality were analysed over a median follow-up of 27 months (interquartile range 16-43 months).. Predictive performance was more accurate when NT-proBNP and eGFR were used, resulting in effective survival stratification: 64.4 months for stage 1, 44.6 months for stage 2, and 20.5 months for stage 3 (P < 0.01 for stages 1 vs 2; P < 0.0001 for stages 1 vs 3; P < 0.0001 stages 2 vs 3). The combination of NT-proBNP and TnI was unable to effectively differentiate survival: 64.5 months for stage 1, 50.9 months for stage 2, and 27.3 months for stage 3 (P = 0.223 for stages 1 vs 2; P < 0.0001 for stages 1 vs 3; P < 0.0001 for stages 2 vs 3). The same results were seen after age adjustment.. A staging system using NT-proBNP and eGFR had better prognostic accuracy for ATTR-CA patients compared with one using NTproBNP and TnI.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Female; Glomerular Filtration Rate; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Severity of Illness Index; Troponin I

Evidence links markers of systemic inflammation and heart failure (HF) with ventricular arrhythmias (VA) and/or death. Biomarker levels, and the risk they indicate, may vary over time. We evaluated the utility of serial laboratory measurements of inflammatory biomarkers and HF, using time-dependent analysis.. We prospectively enrolled ambulatory patients with left ventricular ejection fraction (LVEF) ≤35% and a primary-prevention implanted cardioverter-defibrillator (ICD). Levels of established inflammatory biomarkers [C-reactive protein, erythrocyte sedimentation rate (ESR), suppression of tumourigenicity 2 (ST2), tumour necrosis factor alpha (TNF-α)] and brain natriuretic peptide (BNP) were assessed at 3-month intervals for 1 year. We assessed relationships between biomarkers modelled as time-dependent variables, VA, and death. Among 196 patients (66±14 years, LVEF 23±8%), 33 experienced VA, and 18 died. Using only baseline values, BNP predicted VA, and both BNP and ST2 predicted death. Using serial measurements at 3-month intervals, time-varying BNP independently predicted VA, and time-varying ST2 independently predicted death. C-statistic analysis revealed no significant benefit to repeated testing compared with baseline-only measurement. C-reactive protein, ESR, and TNF-α, either at baseline or over time, did not predict either endpoint.. In stable ambulatory patients with systolic cardiomyopathy and an ICD, BNP predicts ventricular tachyarrhythmia, and ST2 predicts death. Repeated laboratory measurements over a year's time do not improve risk stratification beyond baseline measurement alone.. Clinicaltrials.gov NCT01892462 (https://clinicaltrials.gov/ct2/show/NCT01892462).

Topics: Biomarkers; Cardiomyopathies; Heart Failure; Humans; Inflammation; Natriuretic Peptide, Brain; Prognosis; Stroke Volume; Ventricular Function, Left

Currently, the pathogenesis of congestive heart failure (CHF) in cats is not fully understood.. To identify novel biomarkers for CHF in cats caused by primary cardiomyopathy, particularly related to cardiovascular-renal axis disorder and systemic inflammatory response.. Twenty-five cats in CHF caused by primary cardiomyopathy, 12 cats with preclinical cardiomyopathy, and 20 healthy controls.. Case control and observational case series. The following serum biomarkers were compared among the 3 cat groups: a cardiorenal profile that included N-terminal pro-brain natriuretic peptide (NT-proBNP), symmetric dimethylarginine (SDMA), and creatinine and an inflammatory profile that included 7 acute-phase proteins (APPs). Survival analyses and longitudinal studies were performed in CHF cats.. All cardiorenal biomarkers were positively correlated and higher in CHF cats, and high NT-proBNP and SDMA were associated with poor clinical outcome. Cats with CHF had significantly higher leucine-rich alpha-2-glycoprotein 1, serum amyloid A, and ceruloplasmin, and these APPs were positively correlated with NT-proBNP and left atrial size. In a multivariable survival analysis, alpha-1-acid glycoprotein concentration (P = .01), body weight (P = .02) and left atrial-to-aortic root ratio (P = .01) were independent prognostic factors for CHF in these cats.. In cats, CHF is an inflammatory disorder and outcome in CHF may be determined by the extent of inflammation and possibly the amount of residual renal function. These novel biomarkers have potential use for the clinical management, prognosis, and future research into CHF and cardiomyopathy in cats.

Topics: Acute-Phase Proteins; Animals; Arginine; Biomarkers; Cardiomyopathies; Case-Control Studies; Cat Diseases; Cats; Creatinine; Female; Heart Failure; Inflammation; Kidney Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments

Topics: Amyloidosis; Bone and Bones; Cardiomyopathies; Heart; Humans; Natriuretic Peptide, Brain

Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.. PHäNOTYPISIERUNG UND RISIKOSTRATIFIZIERUNG BEI COVID-19: Die aktuelle COVID-19-Erkrankung verläuft in 3 Stadien. Einige Serum-Biomarker können einem der 3 Stadien zugeordnet werden und es besteht ein Zusammenhang mit der Mortalität. Laborwerte können insbesondere bei serieller Erfassung helfen, Aussagen zur Schwere der Erkrankung und Prognose zu liefern. In Zukunft könnten diese dann ggf. zur Steuerung der Therapie genutzt werden. COVID-19-KARDIOVASKULäRE ERKRANKUNGEN UND MYOKARDSCHADEN:  Biomarker von Myokardschaden (high-sensitives kardiales Troponin, hs-cTn) oder hämodynamischem Stress (NT-proBNP) können bei COVID-19, wie bei anderen Pneumonien, auftreten und korrelieren mit der Schwere und Prognose der Grunderkrankung. Bei hospitalisierten Patienten mit COVID-19 erklären sich milde Erhöhungen von hs-cTn oder NT-proBNP durch deren kardiovaskuläre Komorbidität und durch die direkte oder indirekte akute Herzschädigung bzw. den Stress durch und während der COVID-19-Pneumonie. Bei gegebenem Verdacht auf einen Nicht-ST-Hebungsinfarkt und COVID-19 sollte eine sorgfältige Abwägung der Indikation für eine Echokardiografie und invasive Diagnostik gegen das Risiko der Kontamination abgewogen werden.

Topics: Adult; Biomarkers; Cardiomyopathies; Comorbidity; Coronavirus Infections; COVID-19; Humans; Male; Natriuretic Peptide, Brain; Pandemics; Peptide Fragments; Phenotype; Pneumonia, Viral; Risk; Troponin C

Myocardial infarction (MI) increases myocardial fibrosis (MF) and subsequent cardiac remodeling. Cholecystokinin octapeptide (CCK-8) is expressed in cardiomyocytes and plays an important role in cardiovascular regulation. In this study, we intend to use a rat model of myocardial infarction to evaluate the effects of CCK-8 on myocardial fibrosis and cardiac remodeling.. Male Sprague-Dawley rats were separated into 3 groups: sham operation, MI + NaCl, and MI + CCK-8. All rats were subjected to left coronary artery ligation to induce MI or sham operation and then treated with CCK-8 or saline for 28 days. After 4 weeks, echocardiography was performed to assess cardiac function and myocardial fibrosis was evaluated using H&E and Masson's Trichrome-stained sections. The levels of BNP, CCK-8 in the plasma of all rats were detected by ELISA; RNA sequencing (RNA-seq) analysis was also adapted to detect differentially expressed genes in myocardial tissues of each group. Myocardial expression of fibrosis markers was analyzed by western blotting, immunohistochemistry and qRT-PCR.. CCK-8 was demonstrated to improve left ventricular function and results of H&E staining, Masson's trichrome staining, immunohistochemistry and western blotting showed that CCK-8 attenuated MF. Gene expression profiles of the left ventricles were analysed by RNA-seq and validated by qRT-PCR. Cardiac fibrosis genes were downregulated by CCK-8 in the left ventricle.. CCK-8 can alleviate fibrosis in the noninfarcted regions and delay the left ventricular remodeling and the progress of heart failure in a MI rat model.

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Echocardiography; Gene Expression Regulation; Heart Ventricles; Male; Myocardial Infarction; Myocytes, Cardiac; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; RNA-Seq; Sincalide; Ventricular Remodeling

The present study was to evaluate the feasibility of using the multi-biomarker strategy for the prediction of sepsis-induced myocardial dysfunction (SIMD) and mortality in septic patients.. Brain natriuretic peptide (BNP), cardiac troponin I (cTnI), and heart-type fatty acid-binding protein (h-FABP) in 147 septic patients were assayed within 6 h after admission. We also determined the plasma levels of myeloperoxidase (MPO) and pregnancy-associated plasma protein-A (PAPP-A). The receiver operating characteristic (ROC) curve was used to assess the best cutoff values of various single-biomarkers for the diagnosis of SIMD and the prediction of mortality. Also, the ROC curve, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) indices were used to evaluate the feasibility of using multi-biomarkers to predict SIMD and mortality.. Our statistics revealed that only h-FABP independently predicted SIMD (P<0.05). The addition of MPO and cTnI to h-FABP for SIMD prediction provided an NRI of 18.7% (P=0.025) and IDI of 3.3% (P=0.033). However, the addition of MPO or cTnI to h-FABP did not significantly improve the predictive ability of h-FABP to SIMD, as evidenced by the area under the curve (AUC), NRI, and IDI (all P>0.05). A history of shock and MPO were independent predictors of mortality in septic patients (both P<0.05). The addition of PAPP-A and h-FABP to MPO resulted in a mortality prediction with NRI of 25.5% (P=0.013) and IDI of 2.9% (P=0.045). However, this study revealed that the addition of h-FABP or PAPP-A to MPO did not significantly improve the ability to predict mortality, as evidenced by the AUC, NRI, and IDI (all P>0.05).. The findings of this study indicate that a sensitive and specific strategy for early diagnosis of SIMD and mortality prediction in sepsis should incorporate three biomarkers.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathies; Fatty Acid-Binding Proteins; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peroxidase; Pregnancy-Associated Plasma Protein-A; Sepsis; Troponin I

Background Duchenne muscular dystrophy (DMD) is a neuromuscular disorder caused by mutations within the dystrophin gene. DMD is characterized by progressive skeletal muscle degeneration and atrophy and progressive cardiomyopathy. It has been observed the severity of cardiomyopathy varies in patients with DMD. Methods and Results A cohort of male patients with DMD and female DMD carriers underwent whole exome sequencing. Potential risk factor variants were identified according to their functional annotations and frequencies. Cardiac function of 15 male patients with DMD was assessed by cardiac magnetic resonance imaging, and various cardiac magnetic resonance imaging parameters and circulating biomarkers were compared between genotype groups. Five subjects carrying potential risk factor variants in the cystic fibrosis transmembrane regulator gene demonstrated lower left ventricular ejection fraction, larger left ventricular end-diastolic volume, and higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels compared with 10 subjects who did not carry the potential risk factor variants (

Topics: Adult; Cardiomyopathies; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Dystrophin; Exome Sequencing; Female; Genetic Predisposition to Disease; Heart Function Tests; Humans; Magnetic Resonance Imaging, Cine; Male; Muscular Dystrophy, Duchenne; Mutation, Missense; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Dysfunction, Left

This study aims at estimating the prevalence of cirrhotic cardiomyopathy in a cohort of cirrhosis patients in northern India using the World Congress of Gastroenterology 2005 criteria and its relationship with grades of cirrhosis, its complications, and all-cause mortality.. This was a prospective study in which 53 cirrhosis patients underwent the 2D color Doppler, and tissue Doppler echocardiography. Echocardiography findings were compared with thirty age- and sex-matched healthy controls. Additionally, serum pro-brain natriuretic peptide (pro-BNP) and troponin-T levels were measured. Patients were followed up for 6 months to look for complications and mortality.. 2D echocardiography findings revealed that diastolic cardiomyopathy with no gross systolic dysfunction was significantly prevalent in cirrhosis patients. Using the Montreal criteria, we found the incidence of diastolic cardiomyopathy to be 56.6%. Tissue Doppler echocardiography findings were also correlated. Diastolic dysfunction correlated with the severity of cirrhosis, and patients with higher Child score had more diastolic dysfunction. Serum pro-BNP levels and QTc interval were also higher in patients with diastolic dysfunction. On survival analysis, patients with cirrhotic cardiomyopathy had shorter survival and greater frequency of encephalopathy and hepatorenal syndrome (HRS) episodes as compared with cirrhotic patients without cardiomyopathy, though the differences were not statistically significant.. The study showed that diastolic dysfunction was highly prevalent (56.6% of the study population) in cirrhosis patients. QTc interval and pro-BNP were also significantly raised. Also, complications of cirrhosis like HRS, spontaneous bacterial peritonitis, and hepatic encephalopathy were more common in the cirrhotic cardiomyopathy group.

Topics: Bacterial Infections; Biomarkers; Cardiomyopathies; Echocardiography, Doppler; Female; Follow-Up Studies; Hepatorenal Syndrome; Humans; India; Liver Cirrhosis; Male; Natriuretic Peptide, Brain; Peptide Fragments; Peritonitis; Prevalence; Prospective Studies; Time Factors

The presented data show that tacotsubo syndrome (TS) is characterized by the absence of coronary artery obstruction, cardiac contractile dysfunction, apical ballooning, and heart failure, and in some patients, ST-segment elevation and prolongation of the QTc interval. Every tenth patient with TS develops ventricular arrhythmias. Most of TS patients have elevated markers of necrosis (troponin I, troponin Т, and creatine kinase МВ (CK-МВ), which are considerably lower than in patients with acute myocardial infarction (AMI) with ST-segment elevation. The level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), in contrast, is considerably higher in patients with TS than with AMI. Differential diagnosis of TS and AMI should be based on a multifaceted approach using coronary angiography, echocardiography, analysis of ECG, magnetic resonance imaging, single-photon emission computed tomography, and measurement of troponins, CK-MB, and NT-proBNP.

Topics: Biomarkers; Cardiomyopathies; Diagnosis, Differential; Electrocardiography; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Takotsubo Cardiomyopathy; Troponin T

Early diagnosis of cardiac involvement is a key issue in the management of AL amyloidosis. Our objective was to establish a diagnostic score of cardiac involvement in AL amyloidosis and to compare it with the current consensus criteria [i.e. left ventricular hypertrophy >12 mm and N-terminal pro b-type natriuretic peptide (NT-proBNP) >332 ng/L].. We carried out a prospective and multicenter study on AL amyloidosis patients who underwent cardiac evaluation including clinical examination, electrocardiography (ECG), cardiac biomarkers, transthoracic echocardiography (TTE), and cardiac magnetic resonance imaging (CMR). Cardiac involvement was based on CMR and/or endomyocardial biopsy. In a derivation cohort of 114 patients (82 with cardiac involvement), the highest diagnostic accuracy was observed with NT-proBNP and troponin blood levels, TTE-derived global longitudinal strain (LS), and apical to basal LS gradient. By using multivariate analysis, we established a diagnostic score including global LS ≥-17% (1 point), apical/(basal + median) LS ≥0.90 (1 point), and troponin T >35 ng/L (1 point). A score >1 was associated with sensitivity of 94% and specificity of 97%, an area under the curve of 0.98 [95% confidence interval (CI) 0.93-0.99] as well as a net reclassification index of 0.39 (95% CI 0.28-0.46) when compared with consensus criteria. In a validation cohort of 73 AL amyloidosis patients, the area under the receiver operating characteristic curve of the diagnostic score was 0.97 (95% CI 0.90-0.99).. Combining T troponin blood levels and two echo-derived strain parameters leads to very high accuracy for diagnosing cardiac involvement in AL amyloid patients.

Topics: Amyloidosis; Biomarkers; Cardiomyopathies; Echocardiography; Humans; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Troponin T

Light Chain (AL) and transthyretin (ATTR) amyloidosis are the most common forms of amyloid cardiomyopathy. Population based studies describing the epidemiology and clinical features of amyloid cardiomyopathy are often based in tertiary medical centers and thus may be limited by referral bias.. We performed a cohort study of 198 patients diagnosed and treated in the Kaiser Permanente Northern California health care system who had a confirmed diagnosis of cardiac amyloidosis between 2001 and 2016. Associations between demographic, clinical, laboratory and imaging data and patient outcomes were quantified using multivariable Cox proportional hazard models for both the AL and ATTR groups. The average length of follow up was 2.8 years (SD 2.9 years) and overall survival was 69.1 percent at one year and 35.4 percent at five years. In the AL group, lower left ventricular ejection fraction (HR 1.33 per 5-point decrease, P < .001), coronary artery disease (HR 3.56, P < .001), and diabetes mellitus (HR 3.19, P < .001) were associated with all-cause mortality. Increasing age at the time of diagnosis with associated with higher all-cause mortality in both the AL and ATTR groups. Higher levels of B-type natriuretic peptide were associated with all-cause mortality in both groups: Top quartile BNP HR 6.17, P < .001 for AL and HR 8.16, P = .002 for ATTR.. This study describes a large cohort of patients with amyloid cardiomyopathy derived from a community based, integrated healthcare system and describes demographic, clinical, and laboratory characteristics associated with mortality and heart failure hospitalization. In this population, coronary artery disease, diabetes mellitus, and high BNP levels were strongly associated with mortality.

Topics: Age Factors; Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; California; Cardiomyopathies; Cause of Death; Cohort Studies; Coronary Artery Disease; Delivery of Health Care, Integrated; Diabetes Mellitus; Echocardiography; Female; Heart Failure; Hospitalization; Humans; Immunoglobulin Light-chain Amyloidosis; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Proportional Hazards Models; Stroke Volume; Treatment Outcome

Heart Failure (HF) is accompanied by a high cost of care and gloomy prognosis despite recent advances in its management. Therefore, efforts to minimize HF rehospitalizations is a major focus of several studies.. We conducted a retrospective cohort study of 140 patients 18 years and above who had baseline clinical parameters, echocardiography, NT-ProBNP, troponin I and other laboratory parameters following a 3-year electronic medical record review. Patients with coronary artery disease, preserved ejection fraction, pulmonary embolism, cancer, and end-stage renal disease were excluded.. Of the 140 patients admitted with HF with reduced Ejection Fraction (HFrEF) secondary to non-ischemic cardiomyopathy, 15 were re-hospitalized within 30 days of discharge while 42 were rehospitalized within 6 months after discharge for decompensated HF. Receiver operating characteristic (ROC) cutoff points were obtained for NT-ProBNP at 5178 pg/ml and serum troponin I at 0.045 ng/ml. After Cox regression analysis, patients with HFrEF who had higher hemoglobin levels had reduced odds of re-hospitalization (p = 0.007) within 30 days after discharge. NT-ProBNP and troponin I were independent predictors of re-hospitalization at 6 months after discharge (p = 0.047 and p = 0.02), respectively, after Cox regression analysis.. Troponin I and NT-ProBNP at admission are the best predictors of re-hospitalization 6 months after discharge among patients with HFrEF. Hemoglobin is the only predictor of 30 -day rehospitalization among HFrEF patients in this study. High-risk patients may require aggressive therapy to improve outcomes.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiomyopathies; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Stroke Volume; Troponin I

Cardiac sarcoidosis (CS) is a potentially life-threatening condition. Early detection of CS is therefore important. The aim of this study was to eludicate the usefulness of different investigations in a subgroup of patients with sarcoidosis regarded as having an increased risk for cardiac involvement.. 42 sarcoidosis patients, who had an abnormal resting electrocardiogram (ECG) and/or symptoms indicating possible cardiac involvement (i.e. palpitations, pre-syncope or syncope), were included in the study. They were identified in a consecutive manner among patients followed-up at outpatient clinics for respiratory disorders. Holter monitoring, exercise test, transthoracic echocardiogram (TTE), cardiovascular magnetic resonance (CMR) and analysis of N-terminal pro B-type natriuretic peptide (NT-pro-BNP) in serum were performed. Note, that the role of FDG-PET was not investigated in this study.. In the group with a pathologic ECG 11/25 (44%) were ultimately diagnosed with CS (all with pathologic CMR). However, in the group with only symptoms but a normal ECG just 1/17 got the diagnosis CS (p<0.05). This patient had a pathologic Holter monitoring. The risk for CS was increased if serum NT-pro-BNP was elevated (i.e. NT-pro-BNP>125 ng/L), sensitivity 78% (p<0.05), specificity 67%. By adding a pathologic ECG to an elevated NT-pro-BNP increased specificity to 93% and sensitivity remained at 78%.. Our findings indicate that CMR should be performed at an early stage in sarcoidosis patients with an abnormal resting ECG. Holter monitoring and elevated levels of NT-pro-BNP may enhance the diagnostic accuracy whereas exercise testing and TTE in this study had less impact on the identification of CS.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Diagnostic Techniques, Cardiovascular; Early Diagnosis; Echocardiography; Electrocardiography, Ambulatory; Exercise Test; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Reproducibility of Results; Sarcoidosis; Sweden

We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF).. Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions.. CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

Topics: Aged; Cardiac Resynchronization Therapy; Cardiomyopathies; Exercise; Female; Fourier Analysis; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radionuclide Angiography; Research Design; Rest; Technetium; Ventricular Dysfunction, Right; Ventricular Function, Right

Cardiac involvement in systemic lupus erythematosus (SLE) is often undiagnosed in its early phases. Specific heart biomarkers may identify patients at risk. We sought to investigate the prevalence and associated factors for such biomarkers in SLE.. Brain natriuretic peptide (BNP) and cardiac troponin I (cTnI) were measured simultaneously in 151 consecutive patients with no history of heart disease or pulmonary arterial hypertension (PAH). None had electrocardiographic abnormalities suggestive of acute coronary syndrome. Cross-sectional comparisons and logistic regression analyses were performed. Patients with abnormal biomarkers were investigated to delineate the specific cause.. Sixteen patients (16/151, 10.6%) had elevated BNP, and 9 of them also had abnormal cTnI. Compared to subjects with normal biomarkers, they were older, had longer disease and antimalarial (AM) use duration, and more frequently persistent creatine phosphokinase (CPK) elevation. Multivariable regression analysis showed prolonged AM treatment (> 5.6 yrs) and persistent CPK elevation to be important predictors for elevated cardiac biomarkers. Six patients were diagnosed with definite (based on endomyocardial biopsy, n = 2) or possible (based on cardiac magnetic resonance after exclusion of other causes) AM-induced cardiomyopathy (AMIC); all had both BNP and cTnI elevated. Alternative causes were identified in 5, while no definitive diagnosis could be made in the remaining patients.. About 10% of patients with SLE had elevated myocardial biomarkers, in the absence of prior cardiac disease or PAH. One-third of them were diagnosed with AMIC. Prolonged AM therapy and persistent CPK elevation conferred an increased risk for abnormal BNP and cTnI, which might predict AMIC.

Topics: Adult; Aged; Antimalarials; Biomarkers; Cardiomyopathies; Creatine Kinase; Cross-Sectional Studies; Female; Humans; Lupus Erythematosus, Systemic; Malaria; Male; Middle Aged; Natriuretic Peptide, Brain; Risk Factors; Troponin I

Present study aims to explore the pathophysiological role of microRNA (miR)-29a in the process of obesity-related cardiomyopathy in human subjects and mice.. The expression level of circulating exosomal miR-29a was measured in 37 lean and 30 obese human subjects, and correlated with cardiac parameters. The effects of miR-29a on mitochondrial activity and cardiac function were investigated by treatment of miR-29a sponge in primary mouse cardiomyocytes and diet-induced obesity-related cardiomyopathy in mice.. The increased circulating miR-29a level was closely associated with impaired human cardiac function, including ejection fraction (r = -0.2663, p < 0.05) and NT-proBNP levels (r = 0.4270, p < 0.001). Exosomes from obese human plasma mediated cardiomyocyte mitochondrial inactivity, but pre-treatment with miR-29a sponge attenuated the exosomal miR-29a-induced reduction of ATP production (p < 0.001), basal oxygen consumption (p < 0.01) and mitochondrial complex I activity (p < 0.01). In vivo mouse study, high fat diet damaged cardiac function, normal structure, and mitochondrial activity, whereas miR-29a sponge improved the cardiac status.. Present study uncovered the correlation between circulating miR-29a and cardiac parameters in human subjects, and provided solid evidence of the therapeutic application of miR-29a sponge in combating obesity-mediated cardiac dysfunction.

Topics: Animals; Cardiomyopathies; Diet, High-Fat; Exosomes; Humans; Male; Mice, Inbred C57BL; MicroRNAs; Middle Aged; Mitochondria, Heart; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Stroke Volume

Antimalarials (AM) are recommended for all systemic lupus erythematosus (SLE) patients without specific contraindications. Their main adverse effect is retinal damage; however, heart disease has been described in isolated cases. The aim of our study is to describe 8 patients with AM-induced cardiomyopathy (AMIC) in a defined SLE cohort.. Patients attending the Toronto Lupus Clinic and diagnosed with definite (based on endomyocardial biopsy; EMB) and possible AMIC were included [based on cardiac magnetic resonance imaging (cMRI) and other investigations].. Eight female patients (median age 62.5 yrs, disease duration 35 yrs, AM use duration 22 yrs) were diagnosed with AMIC in the past 2 years. Diagnosis was based on EMB in 3 (extensive cardiomyocyte vacuolation, intracytoplasmic myelinoid, and curvilinear bodies). In 4 patients, cMRI was highly suggestive of AMIC (ventricular hypertrophy and/or atrial enlargement and late gadolinium enhancement in a nonvascular pattern). Another patient was diagnosed with complete atrioventricular block, left ventricular and septal hypertrophy, along with concomitant ocular toxicity. All patients had abnormal cardiac troponin I (cTnI) and brain natriuretic peptide (BNP), whereas 7/8 also had chronically elevated creatine phosphokinase. During followup, 1 patient died from refractory heart failure. In the remaining patients, hypertrophy regression and a steady decrease of heart biomarkers were observed after AM cessation.. Once considered extremely rare, AMIC seems to be underrecognized, probably because of the false attribution of heart failure or hypertrophy to other causes. Certain biomarkers (cTnI, BNP) and imaging findings may lead to early diagnosis and enhance survival.

Topics: Aged; Antimalarials; Biomarkers; Biopsy; Canada; Cardiomyopathies; Female; Follow-Up Studies; Humans; Lupus Erythematosus, Systemic; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Rare Diseases; Troponin I; Withholding Treatment

Topics: Biomarkers; Cardiomyopathies; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Reproducibility of Results; Severity of Illness Index; Troponin T

Since mitochondria are energy-generating micro-organisms, most of the disorders in patients with mitochondrial diseases (mt-disease) are considered secondary to defects in ATP synthesis, although some other factors such as reactive oxygen species may be involved. A simultaneous oral administration of febuxostat and inosine was reported to elevate both hypoxanthine and ATP levels in peripheral blood. Based on those results, we attempted co-administration of febuxostat and inosine in two patients with mitochondrial disease: one patient with mitochondrial cardiomyopathy and the other patient with mitochondrial diabetes. In the former case, brain natriuretic peptide (BNP), which is a specific marker for heart failure, was decreased by 31%, and in the latter case, the insulinogenic index increased 3.1 times, suggesting the favorable action of the treatment. Considering that there is no effective treatment available for this disorder, the present therapy may be quite useful for the management of patients with mitochondrial diseases.

Topics: Adenosine Triphosphate; Aged, 80 and over; Cardiomyopathies; Diabetes Mellitus; Febuxostat; Female; Humans; Hypoxanthine; Inosine; Male; Middle Aged; Mitochondria; Mitochondrial Diseases; Natriuretic Peptide, Brain; Reactive Oxygen Species

The longer survival of patients with Duchenne muscular dystrophy due to advances in clinical care has increased the incidence of Duchenne muscular dystrophy-associated cardiomyopathy, a nearly consistent feature in the third decade of life. A 26-year-old patient with Duchenne muscular dystrophy experienced severe acute heart failure triggered by pneumonia. Levosimendan was effective in improving heart function.

Topics: Acute Disease; Adult; Cardiomyopathies; Cardiotonic Agents; Heart Failure; Humans; Lactic Acid; Male; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain; Pneumonia; Simendan

The aim of this study was to compare the prevalence of diastolic dysfunction between the 2016 American Society of Echocardiography (ASE)/European Association of Cardiovascular Imaging and 2009 ASE/European Association of Echocardiography recommendations in patients undergoing living-donor liver transplantation (LDLT).. A total of 312 adult patients who underwent LDLT at our hospital from January 2010 to December 2017 were retrospectively analyzed. Exclusion criteria were systolic dysfunction, arrhythmia, myocardial ischemia, and mitral or aortic valvular insufficiency.. The study population was largely male (68.3%), and the median age was 54 (49-59) years. The median model for end-stage liver disease score was 12 (6-22) points. A predominant difference in the prevalence rates of diastolic dysfunction was observed between the two recommendations. The prevalence rates of diastolic dysfunction and indeterminate diastolic function were lower according to the 2016 recommendations than the 2009 recommendations. The level of concordance between the two recommendations was poor. The proportion of patients with a high brain natriuretic peptide level (> 100 pg/mL) decreased significantly during surgery in the normal and indeterminate groups according to the 2009 recommendations; however, only the normal group showed an intraoperative decrease in the proportion according to the 2016 recommendations. Patients with diastolic dysfunction showed a poorer overall-survival rate than those with normal function according to both recommendations. However, there was a difference in the survival rate in the indeterminate group between the two recommendations. A significant difference in patient survival rate was observed between the dysfunction and indeterminate groups according to the 2009 recommendations; however, the difference was not significant in the 2016 recommendations.. The 2016 classification may be better able to identify patients with a risk for diastolic dysfunction. Particularly, patients in the 2016 indeterminate group seemed to require a cardiac diastolic functional evaluation more frequently during and after surgery than those in the 2009 indeterminate group.

Topics: Biomarkers; Cardiomyopathies; Echocardiography; Female; Heart Failure, Diastolic; Humans; Liver Cirrhosis; Liver Transplantation; Living Donors; Male; Middle Aged; Natriuretic Peptide, Brain; Postoperative Complications; Practice Guidelines as Topic; Preoperative Period; Prevalence; Prognosis; Retrospective Studies; Risk Assessment; Societies, Medical; Survival Rate; Treatment Outcome

Doxorubicin-induced (DXR) cardiomyopathy is a serious health issue in oncology patients. Effective treatment of this clinical situation still remains to be discovered. In this experimental animal study, we aimed to define therapeutic effects of liraglutide, oxytocin and granulocyte colony-stimulating factor in DXR-induced cardiomyopathy model. 40 male Sprague-Dawley rats were included to study. 32 rats were given doxorubicin (DXR) for cardiomyopathy model. DXR was administered intraperitonally (i.p.) at every other day of 2.5 mg/kg/day at six times. Eight rats were taken as normal group and no treatment was performed. 32 rats given doxorubicin were divided into 4 groups. Group 1 rats were assigned to a placebo group and was given with a 0.9% NaCl saline solution at a dose of 1 ml/kg/day i.p. (DXR + saline), Group 2 rats were given with 1.8 mg/kg/day of Liraglutide i.p. (DXR + LIR), Group 3 rats were given with 160 μg/kg/day oxytocin i.p. (DXR + OX), Group 4 rats were given with 100 μg/kg/day filgrastim i.p. (DXR + G-CSF). All medications were given for 15 days. On day 16, under anesthesia, ECG was recorded from derivation I. After that, blood samples were taken by tail vein puncture for biochemical analysis. Finally, the animals were euthanized and the heart removed and prepared for immunohistochemical examination. All three treatments were shown to ameliorate the toxic effect of doxorubicin in cardiac tissue with the best results in DXR + OX group. DXR + OX group had the most preserved tissue integrity examined by light microscopy, least immune expression level of CASPASE-3 (5.3 ± 0.9) (p < 0.001) the highest ECG QRS wave voltage amplitude (0.21 ± 0.008 mV) (p < 0.00001) least plasma MDA (115.3 ± 19.8 nm) (p < 0.001), TNF-alpha (26.6 ± 3.05 pg/ml) (p < 0.001), pentraxin-3 (2.7 ± 0.9 ng/ml) (p < 0.001), Troponin T (1.4 ± 0.08 pg/ml) (p < 0.001), pro-BNP (11.1 ± 3.6 pg/ml) (p < 0.001) levels among all three treatment groups. Consistent with previous literature, we found that OX treatment decreased oxidative, apoptotic and inflammatory activity in DXR-induced cardiomyopathy rat model as well as provided better tissue integrity and better results in clinically relevant measures of ECG assessment, plasma Troponin T and pro-BNP levels. LIR and G-CSF treatment caused similar results with less powerful effects. Our findings suggest that with the best results in OX treatment group, all three agents including LIR and G-CSF attenuates DXR-induced cardiomyopathy in

Topics: Animals; Apoptosis; C-Reactive Protein; Cardiomyopathies; Cardiotoxicity; Caspase 3; Disease Models, Animal; Doxorubicin; Granulocyte Colony-Stimulating Factor; Heart Rate; Humans; Inflammation Mediators; Lipid Peroxidation; Liraglutide; Malondialdehyde; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Oxytocin; Rats, Sprague-Dawley; Serum Amyloid P-Component; Signal Transduction; Troponin T; Tumor Necrosis Factor-alpha

Kawasaki disease (KD) vasculitis is an acute febrile illness of childhood characterized by systemic vasculitis of unknown origin, and is the most common cause of acquired heart disease among children in the United States. While  histological evidence of myocarditis can be found in all patients with acute KD, only a minority of patients are clinically symptomatic and a subset demonstrate echocardiographic evidence of impaired myocardial function, as well as increased left ventricular mass, presumed to be due to myocardial edema and inflammation. Up to a third of KD patients fail to respond to first-line therapy with intravenous immunoglobulin (IVIG), and the use of interleukin (IL)-1 receptor antagonist (IL-1Ra, anakinra) is currently being investigated as an alternative therapeutic approach to treat IVIG-resistant patients. In this study, we sought to investigate the effect of IL-1Ra on myocardial dysfunction and its relation to myocarditis development during KD vasculitis. We used the Lactobacillus casei cell-wall extract (LCWE)-induced murine model of KD vasculitis and investigated the effect of IL-1Ra pretreatment on myocardial dysfunction during KD vasculitis by performing histological, magnetic resonance imaging (MRI) and echocardiographic evaluations. IL-1Ra pretreatment significantly reduced KD-induced myocardial inflammation and N-terminal pro B-type natriuretic peptide (NT-proBNP) release. Both MRI and echocardiographic studies on LCWE-injected KD mice demonstrated that IL-1Ra pretreatment results in an improved ejection fraction and a normalized left ventricular function. These findings further support the potential beneficial effects of IL-1Ra therapy in preventing the cardiovascular complications in acute KD patients, including the myocarditis and myocardial dysfunction associated with acute KD.

Topics: Animals; Cardiomyopathies; Disease Models, Animal; Immunoglobulins, Intravenous; Inflammation; Interleukin 1 Receptor Antagonist Protein; Lacticaseibacillus casei; Male; Mice; Mice, Inbred C57BL; Mucocutaneous Lymph Node Syndrome; Myocarditis; Natriuretic Peptide, Brain; Receptors, Interleukin-1; Vasculitis

Cardiac remodeling, after a myocardial insult, often causes progression to heart failure. The relationship between alterations in left ventricular blood flow, including kinetic energy (KE), and remodeling is uncertain. We hypothesized that increasing derangements in left ventricular blood flow would relate to (1) conventional cardiac remodeling markers, (2) increased levels of biochemical remodeling markers, (3) altered cardiac energetics, and (4) worsening patient symptoms and functional capacity. Methods Thirty-four dilated cardiomyopathy patients, 30 ischemic cardiomyopathy patients, and 36 controls underwent magnetic resonance including 4-dimensional flow, BNP (brain-type natriuretic peptide) measurement, functional capacity assessment (6-minute walk test), and symptom quantification. A subgroup of dilated cardiomyopathy and control subjects underwent cardiac energetic assessment. Left ventricular flow was separated into 4 components: direct flow, retained inflow, delayed ejection flow, and residual volume. Average KE throughout the cardiac cycle was calculated.. Patients had reduced direct flow proportion and direct-flow average KE compared with controls ( P<0.0001). The residual volume proportion and residual volume average KE were increased in patients ( P<0.0001). Importantly, in a multiple linear regression model to predict the patient's 6-minute walk test, the independent predictors were age (β=-0.3015; P=0.019) and direct-flow average KE (β=0.280, P=0.035; R. This study demonstrates an independent predictive relationship between the direct-flow average KE and a prognostic measure of functional capacity. Intracardiac 4-dimensional flow parameters are novel biomarkers in heart failure and may provide additive value in monitoring new therapies and predicting prognosis.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Cardiomyopathy, Dilated; Case-Control Studies; Coronary Circulation; Cross-Sectional Studies; Exercise Tolerance; Female; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Ischemia; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Ventricular Function, Left; Ventricular Remodeling; Walk Test

Background Sepsis is the overwhelming host response to infection leading to shock and multiple organ dysfunction. Cardiovascular complications greatly increase sepsis-associated mortality. Although murine models are routinely used for preclinical studies, the benefit of using genetically engineered mice in sepsis is countered by discrepancies between human and mouse sepsis pathophysiology. Therefore, recent guidelines have called for standardization of preclinical methods to document organ dysfunction. We investigated the course of cardiac dysfunction and myocardial load in different mouse models of sepsis to identify the optimal measurements for early systolic and diastolic dysfunction. Methods and Results We performed speckle-tracking echocardiography and assessed blood pressure, plasma inflammatory cytokines, lactate, B-type natriuretic peptide, and survival in mouse models of endotoxemia or polymicrobial infection (cecal ligation and puncture, [ CLP ]) of moderate and high severity. We observed that myocardial strain and cardiac output were consistently impaired early in both sepsis models. Suppression of cardiac output was associated with systolic dysfunction in endotoxemia or combined systolic dysfunction and reduced preload in the CLP model. We found that cardiac output at 2 hours post- CLP is a negative prognostic indicator with high sensitivity and specificity that predicts mortality at 48 hours. Using a known antibiotic (ertapenem) treatment, we confirmed that this approach can document recovery. Conclusions We propose a non-invasive approach for assessment of cardiac function in sepsis and myocardial strain and strain rate as preferable measures for monitoring cardiovascular function in sepsis mouse models. We further show that the magnitude of cardiac output suppression 2 hours post- CLP can be used to predict mortality.

Topics: Animals; Biomarkers; Cardiac Output; Cardiomyopathies; Cytokines; Disease Models, Animal; Disease Progression; Echocardiography, Doppler; Inflammation Mediators; Lactic Acid; Male; Mice, Inbred C57BL; Myocardial Contraction; Natriuretic Peptide, Brain; Predictive Value of Tests; Risk Factors; Sepsis; Time Factors; Ventricular Function, Left

To analyze clinical predictors of mortality in wild-type transthyretin amyloidosis (wt-ATTR).. In total, 191 patients (73.8 ± 0.5 years; 176 males, 15 females) with histologically proven wt-ATTR amyloidosis and genetic exclusion of a transthyretin gene variant were included. Comprehensive clinical characteristics, ECG, biomarkers, and echocardiography were analyzed retrospectively. Strain analyses were performed offline using TomTec Imaging Systems, Germany. Univariable and multivariable analyses predicting all-cause mortality were carried out.. Patients presented with significant heart failure (NYHA 2.5 ± 0.8; NT-proBNP 3644 (4981) pg/ml; LV ejection fraction 45.8 ± 15.0%). LogNT-proBNP correlated with indicators of disease severity. Similar results were obtained for basal and midventricular, but not apical longitudinal strain. During median follow-up of 26.2 ± 1.7 months 46 (25.5%) patients died (40 males, 23%; six females, 40%). In female patients 1-/2-year survival was lower [92.9/67.7%; median survival 30.6 (21.1-40.1) months] when compared to male patients [96.5%/86.6%; median survival 63.9 (45.8-82.0) months]. Parameters associated with survival were NT-proBNP, NYHA class, heart rate, midventricular longitudinal strain, mitral annular plane systolic excursion (MAPSE), Karnofsky Index, systolic blood pressure, estimated glomerular filtration rate. Multivariable analysis revealed MAPSE and NT-proBNP as independent predictors of mortality in the whole cohort and midventricular strain in the subgroup of patients in sinus rhythm.. No sex-specific bias was observed between male and female patients with wt-ATTR regarding age at onset and morphological characteristics. Multivariable analysis revealed MAPSE and NT-proBNP as independent predictors of survival in the whole cohort, whereas midventricular longitudinal strain was the only independent predictor in patients in sinus rhythm.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Biomarkers; Blood Pressure; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Germany; Heart Rate; Humans; Kaplan-Meier Estimate; Karnofsky Performance Status; Male; Mitral Valve; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Retrospective Studies; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Ventricular Function, Left

There are no clear recommendations regarding cirrhotic cardiomyopathy (CC) evaluation in patients with pre-transplant liver cirrhosis. The roles of new methods, tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) in the diagnosis and prognosis of cirrhotic cardiomyopathy remain controversial. We investigated the utility of TDI/STE parameters in cirrhotic cardiomyopathy diagnosis and also in predicting mortality in patients with liver cirrhosis. Left/right ventricular function was studied using conventional TDI (velocities) and STE (strain/strain rate). We assessed left ventricular diastolic dysfunction, graded into four new classes (I/Ia/II/III). Serum NTproBNP (N-terminal prohormone of brain natriuretic peptide), troponin I, β-crosslaps, QTc interval, arterial compliance and endothelial function were measured. Liver-specific scores (Child-Pugh, MELD, MELDNa) were computed. There was a 1-y follow-up visit to determine mortality. We observed resting biventricular diastolic myocardial dysfunction, not presently included in the definition of cirrhotic cardiomyopathy. We provided an improved characterization of cardiac dysfunction in patients with liver cirrhosis. This might change the current definition. However, the utility of STE/TDI parameters in predicting long-term mortality in patients with liver cirrhosis remains controversial.

Topics: Cardiomyopathies; Echocardiography, Doppler; Female; Heart Ventricles; Humans; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Severity of Illness Index; Troponin; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right

Regular health checkups for mothers of patients with Duchenne muscular dystrophy have been performed at National Hospital Organization Tokushima Hospital since 1994. Among 43 mothers participated in this study, 28 dystrophinopathy carriers were identified. Skeletal and cardiac muscle functions of these subjects were examined. High serum creatine kinase was found in 23 subjects (82.1%). Obvious muscle weakness was present in 5 (17.8%) and had progressed from 1994 to 2015. Cardiomyopathy was observed in 15 subjects (60.0%), including dilated cardiomyopathy-like damage that was more common in the left ventricular (LV) posterior wall. Late gadolinium enhancement on cardiac MRI was found in 5 of 6 subjects, suggesting fibrotic cardiac muscle. In speckle tracking echocardiography performed seven years later, global longitudinal strain was decreased in these subjects, indicating LV myocardial contractile abnormality. These results suggest that female dystrophinopathy carriers should receive regular checkups for detection and treatment of cardiomyopathy, even if they have no cardiac symptoms.

Topics: Adult; Cardiomyopathies; Contrast Media; Creatine Kinase; Disease Management; Dystrophin; Electrocardiography; Female; Gadolinium; Humans; Image Processing, Computer-Assisted; Middle Aged; Muscle, Skeletal; Mutation; Natriuretic Peptide, Brain; Neuroimaging; Neurologic Examination; Retrospective Studies

Topics: Atrial Fibrillation; Biomarkers; Brain Ischemia; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Risk Factors; Stroke

Topics: Atrial Fibrillation; Biomarkers; Brain Ischemia; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Risk Factors; Stroke

The impact of excess viral RNA on myocardial function and morphology in the setting of acute human immunodeficiency virus (HIV) infection remains unknown. In this study, 49 patients with acute HIV infection showed increased levels of N-terminal prohormone of brain natriuretic peptide, a surrogate of myocardial function, which decreased with viral suppression and normalization of systemic inflammation (79 pg/mL vs 28 pg/mL; P < .001). A comparable change was seen with levels of troponin T, a marker of morphologic myocardial damage (4.9 ng/L vs 1.5 ng/L; P < .001). In conclusion, we observed significant functional and morphological myocardial impairment during acute HIV infection, fueled by inflammatory activation and extensive viral replication, resulting in a reversible subclinical inflammatory cardiomyopathy.

Topics: Adult; Cardiomyopathies; Female; HIV; HIV Infections; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Troponin T; Viral Load

The outcome of cardiac amyloidosis (CA) has been reported mainly in stable populations; limited data are available in patients referred for acute heart failure (AHF) to an intensive cardiac care unit (ICCU).. To address the characteristics and outcomes of patients with confirmed CA admitted to an ICCU for AHF and then to identify the predictors of evolution to cardiogenic shock.. All patients with CA referred to an ICCU for AHF between 2009 and 2015 were included. The clinical endpoint was 3-month death. Data from the population with cardiogenic shock, obtained in a stable haemodynamic state, were matched with data from a control group to determine predictors of evolution to cardiogenic shock.. Among the 421 patients followed for CA in our expert centre, 46 patients (mean age: 64±14 years; 65% light-chain [AL] CA) were referred to the ICCU for AHF (n=26 with cardiogenic shock). At 3 months, death occurred in 24 (52%) patients, mostly in the cardiogenic shock group (n=21/26, 81%). Most deaths occurred 5 days [interquartile range 3-9 days] after catecholamine infusion and 50% occurred in patients aged<65 years. The majority of deaths were reported in patients with AL CA (n=19/24, 79%). Independent variables associated with in-hospital mortality were cardiogenic shock and uraemia level. N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) concentration obtained in a stable haemodynamic state was the only predictor of short-term evolution to cardiogenic shock (odds ratio: 8.7, 95% confidence interval: 2.2-34.6), with an optimal cut-off of 4040pg/mL (sensitivity=92%; specificity=81%).. The study confirms the dramatic mortality associated with CA when presenting as cardiogenic shock and underlines the limited efficiency of conventional treatments. Given the rapid occurrence of death in a young population, an alternative strategy to dobutamine support should be investigated in patients with elevated NT-proBNP concentration.

Topics: Acute Disease; Aged; Aged, 80 and over; Amyloidosis; Biomarkers; Cardiomyopathies; Chi-Square Distribution; Disease Progression; Female; Heart Failure; Hemodynamics; Hospital Mortality; Humans; Intensive Care Units; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Patient Admission; Peptide Fragments; Registries; Risk Factors; Shock, Cardiogenic; Time Factors; Treatment Outcome

Our aim is to clarify the factors for early diagnosis of cardiac sarcoidosis (CS) in patients with complete atrioventricular block (CAVB) and its impact on cardiac function after corticosteroid therapy.A total of 15 CS patients with CAVB who underwent corticosteroid therapy were retrospectively analyzed. Patients were divided into two groups according to the time from the first CAVB onset to the diagnosis of CS. Clinical characteristics and outcomes were compared between the early diagnosis group (within 1 year; group E, n = 10) and the late diagnosis group (over 1 year; group L, n = 5).The history of extracardiac sarcoidosis (60 versus 0%, P = 0.0440) and abnormal findings on echocardiography (70 versus 0%, P = 0.0256) at the CAVB onset were significantly more frequent in group E than in group L. The change of left ventricular ejection fraction (LVEF) and brain natriuretic peptide (BNP) levels was significantly better in group E than in group L (0.8 ± 2.8 versus -32.4 ± 3.9%, P < 0.0001; -11.1 ± 16.0 versus 161.8 ± 35.8 pg/mL, P = 0.0013, respectively). After corticosteroid therapy, the LVEF and BNP levels were also significantly better in group E than in group L (53.3 ± 10.7 versus 37.0 ± 9.3%, P = 0.0128; 63.0 ± 46.4 versus 458.8 ± 352.0 pg/mL, P = 0.0027).The diagnosis may be delayed in CS patients with CAVB without history of extracardiac sarcoidosis. Abnormal findings on echocardiography contributed to the early diagnosis of CS. Therefore, the diagnosis of CS may be missed or delayed in patients without them. Time delay from the CAVB onset to the CS diagnosis may exacerbate the cardiac function.

Topics: Adult; Atrioventricular Block; Cardiomyopathies; Diagnostic Errors; Early Diagnosis; Echocardiography; Electrocardiography; Female; Glucocorticoids; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; Sarcoidosis; Stroke Volume; Ventricular Function, Left

Preeclampsia is one of the most frequent and difficult illnesses in pregnancy, which jeopardizes both mother and fetus. There are several diagnostic criteria for preeclampsia. However, the preeclampsia-associated myocardial damage has not been described. In this study, we employed reduced uterine perfusion pressure (RUPP) to generate a rat model of preeclampsia for the evaluation of myocardial damage in late-gestation rats. The expressions of cardiac injury markers were analyzed by immunohistochemistry and ELISA. The arterial pressure and myocardial tissue velocities were also measured. The role of interleukin (IL)-6 in RUPP-associated myocardial damage was further explored. The results showed that RUPP rats had significant myocardial damage, as demonstrated by the high expressions of myoglobin, creatine kinase isoenzyme, cardiac troponin I, and brain natriuretic peptide. In addition, RUPP increased the mean arterial pressure and the early transmitral flow velocity to mitral annulus early diastolic velocity ratio (E/Ea). Furthermore, IL-6 deteriorated these abnormalities, whereas inhibition of IL-6 significantly relieved them. In conclusion, our study demonstrated that RUPP rats displayed myocardial damage in an IL-6-dependent manner.

Topics: Animals; Antibodies, Monoclonal, Humanized; Arterial Pressure; Cardiomyopathies; Creatine Kinase, MB Form; Disease Models, Animal; Echocardiography, Doppler, Color; Female; Heart; Interleukin-6; Myocardium; Myoglobin; Natriuretic Peptide, Brain; Perfusion; Pre-Eclampsia; Pregnancy; Random Allocation; Rats, Sprague-Dawley; Troponin I

Enlargement of the left atrium is a non-invasive marker of diastolic dysfunction of the left ventricle, a determinant of prognosis in children with cardiomyopathy. Similarly, N-terminal prohormone brain natriuretic peptide is a useful marker in the management of children with cardiomyopathy and heart failure. The aim of this study is to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide in children with cardiomyopathy.. This was a retrospective study reviewing the medical records of patients <18 years of age, who were diagnosed with cardiomyopathy or acute myocarditis with eventual development of cardiomyopathy. Left atrial volume by transthoracic echocardiogram and pulmonary capillary wedge pressure, a surrogate of left atrial pressure, obtained by means of cardiac catheterisation were analysed. In addition, N-terminal prohormone brain natriuretic peptide levels obtained at the time of the cardiac catheterisation were also reviewed. Statistical analysis was performed to evaluate the association of left atrial pressures with left atrial volume and N-terminal prohormone brain natriuretic peptide levels.. There was a linear correlation of left atrial pressure estimated in the cardiac catheterisation with indexed left atrial volume (r=0.63; p<0.001) and left atrial volume z-scores (r=0.59; p<0.001). We found no statistically significant association between the left atrial pressure and N-terminal prohormone brain natriuretic peptide levels.. Left atrial volume measured non-invasively by echocardiography can be used as a surrogate for left atrial pressure in assessing diastolic dysfunction of the left ventricle in children with cardiomyopathy. The larger the size of the left atrium, worse is the diastolic function of the left ventricle.

Topics: Adolescent; Atrial Pressure; Biomarkers; Cardiac Catheterization; Cardiomyopathies; Child; Child, Preschool; Diastole; Echocardiography; Female; Heart Atria; Humans; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Pulmonary Wedge Pressure; Retrospective Studies; Severity of Illness Index

Peripartum cardiomyopathy (PPCM) is life-threatening and its diagnosis is a challenge. We highlight the clinical characteristics and bio-markers of PPCM and the proper differential diagnosis of peripartum dyspnea to aim to make an early diagnosis available.We analyzed 262 peripartum patients with dyspnea, and summed up the final diagnosis. The clinical data of the control group and the PPCM group as well as before and after the treatment of the PPCM group were compared.In total, 147 (56%) of the perinatal patients were physiologic dyspnea of pregnancy; only 11 (4%) patients met the PPCM diagnostic criteria. Compared with the basic baseline characteristics between the PPCM group and control group, patients with PPCM had a higher heart rate, and the white blood cell, high-sensitivity C-reactive protein (hs-CRP), and B-type natriuretic peptide (BNP) levels were markedly elevated, whereas PaO2 and left ventricular ejection fraction (LVEF) were lower. The heart rate, CRP and BNP levels were lower at the follow-up compared with the pretreatment. Patients who were followed up showed significant improvements in the LVEF and New York Heart Association function class.We standardized the symptoms of dyspnea for calculating, and analyzed the diagnostic efficacy of laboratory indicators. The research highlighted that the use of echocardiography and disease-specific bio-markers may aid in the diagnosis and management.

Topics: Adult; Biomarkers; C-Reactive Protein; Cardiomyopathies; Dyspnea; Female; Heart Rate; Humans; Leukocyte Count; Natriuretic Peptide, Brain; Peripartum Period; Postpartum Period; Puerperal Disorders; Stroke Volume; Young Adult

Topics: Amyloid; Antineoplastic Agents; Bortezomib; Cardiomyopathies; Cyclophosphamide; Dexamethasone; Fatigue; Hepatomegaly; Humans; Image-Guided Biopsy; Immunoglobulin Light-chain Amyloidosis; Immunohistochemistry; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peritoneal Neoplasms; Splenomegaly; Tomography, X-Ray Computed; Treatment Outcome; Weight Loss

Pregnancy is characterized by complex physiological changes of the cardiovascular system. B-type natriuretic peptides, represented by the bioactive molecule (BNP) and its inactive amino terminal fragment (NT-proBNP) are important biomarkers used in the management of the heart failure. Besides cardiac causes, BNP can grow in other noncardiac conditions such as pregnancy. The levels of natriuretic peptides during pregnancy have been the subject of multiple studies, whether it is a normal pregnancy, or there are pre-existing or developed cardiac conditions during pregnancy. It depends on the stage of pregnancy and comorbidities: obesity, preeclampsia, pre-existing cardiomyopathies or peripartum cardiomyopathy. High levels of NT-proBNP in pregnancy are associated with increased risk of cardiovascular events and involve careful supervision of pregnancy, including imaging procedures.

Topics: Biomarkers; Cardiomyopathies; Female; Heart; Heart Diseases; Heart Failure; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Pregnancy; Prognosis; Risk Factors

Topics: Amyloid; Amyloid Neuropathies, Familial; Animals; Biomarkers; Cardiomyopathies; Collagen Type IV; Disease Models, Animal; Doxycycline; Drug Administration Schedule; Drug Therapy, Combination; Gene Expression; Heart; Heat Shock Transcription Factors; Humans; Male; Mice; Mice, Transgenic; Mutation; Natriuretic Peptide, Brain; Peptide Fragments; Prealbumin; Ursodeoxycholic Acid

Heart failure (HF) with reduced ejection fraction remains a major therapeutic challenge. The aim of this study was to investigate the role of novel cardiovascular biomarkers, i.e. soluble suppression of tumorigenicity (sST2), growth-differentiation factor-15 (GDF-15), soluble urokinase plasminogen activator receptor (suPAR) and heart-type fatty acid binding protein (H-FABP) in patients with ischaemic (ICM) or dilative cardiomyopathy (DCM).. A total of 200 patients were enrolled in this study: 65 were diagnosed with DCM and 59 patients suffering from ICM were included. 76 patients without coronary artery disease or signs of heart failure were included as controls. Plasma samples of all patients were analyzed by use of ELISA.. Levels of sST2, suPAR and H-FABP were significantly higher in ICM and DCM patients compared to the control group (p<0.0001). However, there were no significant differences between ICM and DCM in biomarker levels. Ejection fraction correlated inversely with cardiac biomarkers (sST2 p<0.0001, GDF-15 p=0.0394, suPAR p=0.0029, H-FABP p<0.0001). Similarly, CRP levels also showed a positive correlation with cardiac biomarkers. Renal insufficiency (p<0.0001) and diabetes (sST2 p=0.0021, GDF-15 p=0.0055, suPAR p=0.0339, H-FABP p=0.0010) were significantly associated with a rise in cardiac biomarkers.. Novel cardiovascular biomarkers such as ST2, GDF-15, uPAR and H-FABP could offer a great potential for more precise diagnostic in ICM and DCM patients. H-FABP was the most promising marker in our study, followed by sST2, uPAR and GDF-15. Additional prospective studies will be necessary to further evaluate the potential clinical benefits in routine treatment of HF.

Topics: Aged; Biomarkers; Cardiomyopathies; Case-Control Studies; Chronic Disease; Fatty Acid Binding Protein 3; Female; Germany; Growth Differentiation Factor 15; Heart Failure; Humans; Interleukin-1 Receptor-Like 1 Protein; Male; Middle Aged; Natriuretic Peptide, Brain; Receptors, Urokinase Plasminogen Activator; Retrospective Studies; Ventricular Dysfunction, Left

N-terminal prohormone of brain natriuretic peptide (NT-proBNP) concentrations may be increased in cats with various cardiac disorders. The point-of-care (POC) ELISA assay uses the same biologic reagents as the quantitative NT-proBNP ELISA. Previous studies have evaluated the sensitivity and specificity of the POC ELISA in cats with cardiac disease.. To prospectively evaluate the diagnostic utility of the POC ELISA in a select population of cats.. Thirty-eight client-owned cats presented to the University of Florida Cardiology Service for cardiac evaluation. Fifteen apparently healthy cats recruited as part of another study.. Physical examination and echocardiography were performed in all cats. The POC ELISA was assessed visually as either positive or negative by a reader blinded to the echocardiographic findings, and results were analyzed relative to quantitative assay results.. Twenty-six cats were diagnosed with underlying cardiac disease, and 27 cats were considered free of cardiac disease. Cats with cardiac disease included: 21 with hypertrophic cardiomyopathy, 2 with unclassified cardiomyopathy, 2 with restrictive cardiomyopathy, and 1 with 3rd degree atrioventricular (AV) block. The POC ELISA differentiated cats with cardiac disease with a sensitivity of 65.4% and specificity of 100%.. The POC NT-proBNP ELISA performed moderately well in a selected population of cats. A negative test result cannot exclude the presence of underlying cardiac disease, and a positive test result indicates that cardiac disease likely is present, but further diagnostic investigation would be indicated for a definitive diagnosis.

Topics: Animals; Atrioventricular Block; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Case-Control Studies; Cat Diseases; Cats; Enzyme-Linked Immunosorbent Assay; Female; Heart Diseases; Male; Natriuretic Peptide, Brain; Peptide Fragments; Point-of-Care Systems; Sensitivity and Specificity

Topics: Aged; Biomarkers; Cardiomyopathies; Cohort Studies; Female; Glycopeptides; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Pilot Projects; Prognosis; Pulmonary Disease, Chronic Obstructive; Regression Analysis; Severity of Illness Index; Troponin

Among myriad changes occurring during the evolution of heart failure with preserved ejection fraction (HFpEF), cardiomyocyte-extracellular matrix interactions from excess collagen may affect microvascular, mechanical, and electrical function.. To investigate whether myocardial fibrosis (MF) is similarly prevalent both in those with HFpEF and those at risk for HFpEF, similarly associating with disease severity and outcomes.. Observational cohort study from June 1, 2010, to September 17, 2015, with follow-up until December 14, 2015, at a cardiovascular magnetic resonance (CMR) center serving an integrated health system. Consecutive patients with preserved systolic function referred for CMR were eligible. Cardiovascular magnetic resonance was used to exclude patients with cardiac amyloidosis (n = 19).. Myocardial fibrosis quantified by extracellular volume (ECV) CMR measures.. Baseline BNP; subsequent hospitalization for heart failure or death.. Of 1174 patients identified (537 [46%] female; median [interquartile range {IQR}] age, 56 [44-66] years), 250 were "at risk" for HFpEF given elevated brain-type natriuretic peptide (BNP) level; 160 had HFpEF by documented clinical diagnosis, and 745 did not have HFpEF. Patients either at risk for HFpEF or with HFpEF demonstrated similarly higher prevalence/extent of MF and worse prognosis compared with patients with no HFpEF. Among those at risk for HFpEF or with HFpEF, the actual diagnosis of HFpEF was not associated with significant differences in MF (median ECV, 28.2%; IQR, 26.2%-30.7% vs 28.3%; IQR, 25.5%-31.4%; P = .60) or prognosis (log-rank 0.8; P = .38). Over a median of 1.9 years, 61 patients at risk for HFpEF or with HFpEF experienced adverse events (19 hospitalization for heart failure, 48 deaths, 6 with both). In those with HFpEF, ECV was associated with baseline log BNP (disease severity surrogate) in multivariable linear regression models, and was associated with outcomes in multivariable Cox regression models (eg, hazard ratio 1.75 per 5% increase in ECV, 95% CI, 1.25-2.45; P = .001 in stepwise model) whether grouped with patients at risk for HFpEF or not.. Among myriad changes occurring during the apparent evolution of HFpEF where elevated BNP is prevalent, MF was similarly prevalent in those with or at risk for HFpEF. Conceivably, MF might precede clinical HFpEF diagnosis. Regardless, MF was associated with disease severity (ie, BNP) and outcomes. Whether cells and secretomes mediating MF represent therapeutic targets in HFpEF warrants further evaluation.

Topics: Adult; Aged; Cardiomyopathies; Cohort Studies; Disease Progression; Extracellular Space; Female; Fibrosis; Heart; Heart Failure; Humans; Linear Models; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Severity of Illness Index; Stroke Volume; Time Factors

Central arterial stiffness has been shown to play a key role in cardiovascular disease. However, evidence regarding such arterial stiffness from various arterial segments in relation to B-type natriuretic peptide (BNP) remains elusive.. A total of 1255 participants (47.8% men; mean age: 62.6 ± 12.3 [SD] years) with preserved left ventricular function (ejection fraction ≥50%) and ≥1 risk factors were consecutively studied. Arterial pulse wave velocity (PWV) by automatic device (VP-2000; Omron Healthcare) for heart-femoral (hf-PWV), brachial-ankle (ba-PWV), and heart-carotid (hc-PWV) segments were obtained and related to BNP concentrations (Abbott Diagnostics, Abbott Park, IL, USA).. Subjects in the highest hf-PWV quartile were older and had worse renal function and higher blood pressure (all P < 0.05). Elevated PWV (m/s) was correlated with elevated BNP (pg/ml) (beta coefficient = 19.3, 12.4, 5.9 for hf-PWV, ba-PWV, hc-PWV respectively, all p < 0.05). After accounting for clinical co-variates and left ventricle mass index (LVMI), both hf-PWV and ba-PWV were correlated with higher BNP (beta coefficient = 8.3, 6.4 respectively, P < 0.01 for each). Adding both hf-PWV and ba-PWV to LVMI significantly expanded ROC in predicting abnormal BNP>100 pg/ml (both P < 0.01), but only hf-PWV presented significant integrated discrimination improvement to predict risk for BNP concentrations (0.7%, P = 0.029).. A significant segmental PWV associated with biomarker BNP concentrations suggests that arterial stiffness is associated with myocardial damage.

Topics: Adult; Aged; Aged, 80 and over; Blood Pressure; Cardiomyopathies; Female; Humans; Kidney Function Tests; Male; Middle Aged; Natriuretic Peptide, Brain; Stroke Volume; Vascular Stiffness

Topics: Biomarkers; Cardiomyopathies; Diagnostic Imaging; Echocardiography, Stress; Humans; Mass Screening; Morbidity; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Positron-Emission Tomography; Troponin T

INTRODUCTION    Light‑chain (AL) amyloidosis is the most common cardiac amyloidosis. Despite progress in treatment, early mortality remains a substantial problem in these patients. OBJECTIVES    The aim of this study was to determine a clinical profile of patients diagnosed with AL amyloidosis in a cardiology department, as well as to define the cut‑off point for early mortality and identify predictors of early mortality in this population. PATIENTS AND METHODS    The study included 30 patients (14 women; median age, 61.5 years) with AL amyloidosis confirmed by echocardiography and biopsy of 2 organs. RESULTS    Six patients were diagnosed with stage II amyloidosis according to the Mayo 2004 classification, and 24 patients-with stage III. Early mortality was defined as death during 102 days after diagnosis and was observed in 14 patients. Patients who died earlier were younger and more frequently reported a weight loss of more than 10 kg and orthostatic hypotension than patients who died later. Moreover, they had higher concentrations of high‑sensitivity troponin T and N‑terminal pro‑B‑type natriuretic peptide (NT‑proBNP) and worse left and right ventricular (RV) contractility. In the Cox models, the age of less than 64 years, NT‑proBNP levels exceeding 4968 pg/ml, RV end‑diastolic diameter of less than 34 mm, and tricuspid annular plane systolic excursion lower than 13 mm were significant predictors of mortality within 102 days after diagnosis. CONCLUSIONS    We presented the results of the first Polish prospective noninterventional study on AL amyloidosis diagnosed in the cardiology department. We found that patients have advanced disease at the time of diagnosis. Younger age, impaired RV function, and higher concentrations of cardiac markers are predictors of worse prognosis.

Topics: Aged; Biomarkers; Cardiomyopathies; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Proportional Hazards Models; Prospective Studies; Troponin T; Ventricular Dysfunction, Right

To investigate the expression and mechanism of plasma microRNA-21 in patients with ischemic cardiomyopathy (ICM).. 56 cases of ICM patients were selected in our hospital from February 2010 to March 2016 as the observation group, and 60 cases of healthy patients were selected as control group. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of microRNA-21 in two groups. Then, differences of the total cholesterol (TC), triglycerides (TG), left ventricular ejection fraction (LVEF), high and low density lipoprotein cholesterol (HDL-C, LDL-C), left ventricular end-diastolic volume (LVEDV), N terminal B type brain natriuretic peptide (NT-proBNP) and other clinical indicators of the two groups, were compared. The correlation between the plasma microRNA-21 level and the clinical indices was analyzed, and the value of microRNA-21 in the diagnosis and treatment of ICM was evaluated.. The levels of LDL-C, HDL-C and LVEF in the observation group were lower than those in the control group (p<0.05). Plasma microRNA-21, TG, NT-proBNP and LVEDV were higher than those in the control group; the difference was statistically significant (p<0.05). Logistic regression analysis showed that the plasma microRNA-21 level was positively correlated with NT-proBNP and LVEDV (p<0.05).. The expression of microRNA-21 in plasma of patients with ICM was significantly increased. And the expression of micro RNA-21 in plasma was positively correlated with NT-proBNP and LVEDV. Through the ventricular remodeling in ICM patients, it can be used as a new target for the diagnosis and treatment of ICM and a new biomarker for risk assessment.

Topics: Adult; Area Under Curve; Biomarkers; Blood Pressure; Cardiomyopathies; Case-Control Studies; Cholesterol; Female; Humans; Logistic Models; Male; MicroRNAs; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Risk Assessment; ROC Curve; Triglycerides; Ventricular Function, Left; Ventricular Remodeling

Topics: Atherosclerosis; Cardiomyopathies; Humans; Natriuretic Peptide, Brain; Peptide Fragments

Serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) is considered a marker that is expressed in response to myocardial strain and possibly fibrosis. However, the relationship to myocardial fibrosis in a community-based population is unknown.. The authors evaluated the relationship between cardiac magnetic resonance (CMR) measures of fibrosis and NT-proBNP levels in the MESA (Multi-Ethnic Study of Atherosclerosis) study.. A total of 1,334 participants (52% white, 23% black, 11% Chinese, 14% Hispanic, and 52% men with a mean age of 67.6 years) at 6 sites had both serum NT-proBNP measurements and CMR with T1 mapping of indices of fibrosis at 1.5 T. Univariate and multivariable regression analyses adjusting for demographics, cardiovascular risk factors, and left ventricular (LV) mass were performed to examine the association of log NT-proBNP with CMR T1 mapping indices.. In the fully adjusted model, each 1-SD increment (0.44 pg/ml) of log NT-proBNP was associated with a 0.62% increment in extracellular volume fraction (p < 0.001), 0.011 increment in partition coefficient (p < 0.001), and 4.7-ms increment in native T1 (p = 0.001). Results remained unchanged after excluding individuals with clinical cardiovascular disease or late gadolinium enhancement (n = 167), and after replacing LV mass by LV end-diastolic volume in the regression models.. Elevated NT-proBNP is related to subclinical fibrosis in a community-based setting. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Topics: Aged; Aged, 80 and over; Atherosclerosis; Cardiomyopathies; Diastole; Ethnicity; Female; Fibrosis; Heart Ventricles; Humans; Incidence; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; United States; Ventricular Function, Left

Cardiac biomarkers have been studied in sepsis in the past and various mechanisms for their rise have been elucidated. However their association with severity of sepsis, mortality and myocardial dysfunction warrants further studies. We have studied three different cardiac biomarkers- troponin T (trop T), creatine phosphokinase MB isoform (CPK MB) and NT pro brain natriuretic peptide (NT Pro BNP) in patients with septicemia. We have attempted to observe the levels of these biomarkers in sepsis, their individual abilities to predict the severity of sepsis, mortality and association with myocardial dysfunction noted in echocardiography.. There were 54 patients each of septicaemia and controls. The means of the three biomarkers, namely Troponin T, CPK MB and NT Pro BNP, were significantly elevated in patients with sepsis- mean values of 0.23±0.8 ng/ml, 9.9±13.4 ng/ml and 5988.62±13.7 pg/ml respectively. Myocardial dysfunction was observed in 27 cases. There were 13 non-survivors. Troponin T and NT pro BNP were strongly associated with higher mortality. CPK MB had better correlation with myocardial dysfunction.. We conclude that myocardial dysfunction using echocardiography is seen in around half of the patients with sepsis. Cardiac biomarkers can be routinely used in patients of septicemia to suggest the severity of sepsis,to detect myocardial injury and dysfunction and prognostication. CPK MB may be very useful to suspect myocardial dysfunction in such patients.

Topics: Biomarkers; Cardiomyopathies; Creatine Kinase, MB Form; Echocardiography; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sepsis; Troponin T

Whether the optimal cut-off value of left ventricular (LV) reverse remodeling is different in patients with ischemic cardiomyopathy (ICM) vs. non-ischemic cardiomyopathy (NICM) is unclear. This study aimed to clarify this value in patients with ICM and NICM.. LV reverse remodeling was defined as a reduction in LV end-systolic volume (LVESV) at 6 months after cardiac resynchronization therapy (CRT). The clinical endpoint was the combination of cardiac death and first hospitalization for worsening heart failure. Ninety-one of 372 patients had ICM. Event-free survival rates did not differ between ICM and NICM groups (66.8% vs. 78.9%; p=0.12). Receiver operating characteristics analysis revealed a 9% reduction in ESV as the optimal cut-off value to predict the composite endpoint in patients with ICM and a 15% reduction in patients with NICM. Multivariate analysis revealed that reductions in ESV of ≥15% and ≥9% were independent predictors of the composite endpoint, as were left bundle branch block (LBBB) and B-type natriuretic peptide (BNP) at 6 months after CRT. In combination with LBBB and BNP, reduction in ESV ≥9% had a higher, but not significant, C-statistics value than ESV ≥15% (0.854, 95% CI 0.729-0.940 vs. 0.801, 95% CI 0.702-0.908, p=0.07).. The optimal cut-off value of a reduction in LVESV was lower in patients with ICM than in patients with NICM.

Topics: Aged; Bundle-Branch Block; Cardiac Resynchronization Therapy; Cardiomyopathies; Echocardiography; Female; Heart Failure; Heart Ventricles; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Retrospective Studies; Systole; Ventricular Remodeling

This study evaluated whether 2-dimensional speckle-tracking echocardiography (2D-STE) has incremental value for prognosis over traditional clinical, echocardiographic, and serological markers-with main focus on the current prognostic staging system-in light-chain (AL) amyloidosis patients with preserved left ventricular ejection fraction.. Cardiac amyloidosis (CA) is the major determinant of outcome in AL amyloidosis. The current prognostic staging system is based primarily on serum levels of cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain differential (FLC-diff).. Consecutive patients with biopsy-proven AL amyloidosis and left ventricular ejection fraction ≥55% were divided into group 1 with CA (n = 63) and group 2 without CA (n = 87). Global longitudinal strain (GLS) by 2D-STE was performed with Vivid E9 (GE Healthcare Co., Milwaukee, Wisconsin) and syngo Velocity Vector Imaging (VVI) software (Siemens Medical Solutions USA, Inc., Malvern, Pennsylvania) (GLS. Thirty-two deaths (51%) occurred in group 1 and 13 (15%) in group 2 (p ≤ 0.001). Group 1 had thicker walls, lower early diastolic tissue Doppler velocity at septal mitral annulus, and greater left ventricular mass, left atrial volume, glomerular filtration rate, FLC-diff, cTnT, and NT-proBNP (p < 0.001). For the entire cohort, GLS. 2D-STE predicted outcome and provided incremental prognostic information over the current prognostic staging system, especially in the group without CA.

Topics: Aged; Amyloidosis; Biomarkers; Biomechanical Phenomena; Biopsy; Cardiomyopathies; Case-Control Studies; Chi-Square Distribution; Echocardiography, Doppler; Female; Humans; Image Interpretation, Computer-Assisted; Immunoglobulin Light Chains; Kaplan-Meier Estimate; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Stroke Volume; Troponin T; Ventricular Function, Left

Drug-induced cardiomyopathy can be life-threatening in patients with cancer. Our objective was to explore early detection of drug-induced cardiomyopathy in children with cancer. We enrolled pediatric outpatients diagnosed with cancer between 2012 and 2013. In addition, we recruited pediatric outpatients in good general condition without cardiac disease or cancer, as controls. We measured the serum levels of biomarkers and performed chest radiography, electrocardiography, and ultrasound cardiography (UCG). We analyzed left ventricular (LV) torsion and torsion-related parameters using 2-dimensional (2D) speckle tracking on UCG. In total, 35 pediatric patients were enrolled. All patients showed negative findings for plasma troponin T, radiography, and electrocardiography. During 2D speckle tracking, 9 patients were excluded due to inappropriate dynamic echo images. We compared UCG findings between 26 patients and 16 controls. Although there was no difference in ejection fraction between patients and controls, peak LV torsion tended to be lower in patients than in controls, and the absolute basal rotation value at the timing of peak LV torsion was significantly lower in patients than in controls. In conclusion, a decrease of basal rotation in 2D speckle tracking might indicate the initial changes leading to myocardial disorder after chemotherapy.

Topics: Adolescent; Anthracyclines; Antineoplastic Agents; Biomarkers; Bone Marrow Transplantation; Cardiomyopathies; Child; Chronic Disease; Cyclophosphamide; Early Diagnosis; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Maintenance Chemotherapy; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Radiography, Thoracic; Rotation; Stroke Volume; Troponin T

Immune response has been postulated to play a prominent role in the pathogenesis of peripartum cardiomyopathy (PPCM). Given the importance of programmed death (PD)-1 and its ligand B7 homologue 1 (B7-H1) costimulatory molecules as an immune regulatory pathway, this study aimed to investigate the effect of PD-1 and B7-H1 expression on immune response in peripheral blood lymphocytes from the patients with PPCM.. PD-1 and B7-H1 may be involved in modulating immune response in PPCM.. Peripheral blood lymphocytes were obtained from PPCM and pregnancy-matched healthy women. PD-1 and B7-H1 expression were determined using fluorescence quantitative reverse transcription-polymerase chain reactions (RT-PCR) and Western blot. The presence of serum interferon (IFN)-γ and interleukin (IL)-4 were determined with enzyme-linked immunosorbent assay.. The levels of pro-brain natriuretic peptide and IFN-γ were markedly elevated, whereas the levels of left ventricular ejection fraction and IL-4 were significantly reduced in PPCM patients compared to controls. Additionally, both RT-PCR and Western blot revealed that the levels of PD-1 and B7-H1 expression were decreased significantly in PPCM patients compared with controls. A significant positive correlation was observed between PD-1 and B7-H1 expression. Furthermore, PD-1 and B7-H1 expression showed significant negative correlation with IFN-γ, as well as positive correlation with IL-4. Therefore, decreased expression of PD-1 and B7-H1 led to a dysregulating immune response such that cellular immunity linked to T helper (Th)1 cells was predominant over humoral immunity linked to Th2 cells in PPCM.. This study provided the first findings that PD-1 and B7-H1 expression were decreased, which might impair functional regulation of negative costimulation on immune response that may work in the etiopathogenesis of PPCM.

Topics: Adolescent; Adult; B7-H1 Antigen; Cardiomyopathies; Case-Control Studies; Female; Humans; Immunity, Cellular; Immunity, Humoral; Interferon-gamma; Interleukin-4; Natriuretic Peptide, Brain; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Programmed Cell Death 1 Receptor; Th1 Cells; Th2 Cells; Young Adult

Vasoactive cardiovascular hormones such as the N-terminal prohormone of brain natriuretic peptide (NT-proBNP) are produced upon ventricular stretch and play a central role in neurohumoral pathways of the heart regulating cardiovascular remodeling and volume homeostasis. The impact of HIV infection on these neurohumoral pathways of the heart and its potential reversibility by combinations of antiretroviral therapies remain unclear.. We assessed serum levels of NT-proBNP in 219 antiretroviral therapy-naïve HIV-infected patients with a normal cardiac and renal status at treatment initiation and after attainment of viremic control.. Before antiretroviral therapy, NT-proBNP as a surrogate of myocardial function displayed a significant correlation with absolute CD4 cell count (r = -0.31; P < 0.001) as well as with HIV viral load (r = 0.26; P < 0.001). The median levels of NT-proBNP were 80 pg/ml (36-205) in patients with a CD4 cell count less than 200 cells/μl and 42 pg/ml (20-80; P < 0.001) with a CD4 cell count more than 500 cells/μl. After viremic control, no statistical correlation was present.. Higher NT-proBNP levels were observed in treatment-naïve patients with low CD4 cell count and high HIV viral load, indicating a subclinical impact of HIV infection on myocardial function. This association is reversible by the initiation of antiretroviral therapy and subsequent viral suppression.

Topics: Adult; Anti-Retroviral Agents; Biomarkers; Cardiomyopathies; CD4 Lymphocyte Count; Female; HIV Infections; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Viral Load

The use of posttransplant cyclophosphamide (PT-Cy) has contributed significantly to the success of haploidentical hematopoietic cell transplantation (HCT). Furthermore, several studies have shown promising results in the human leukocyte antigen-matched setting. However, the use of high-dose cyclophosphamide has been associated with the development of cardiomyopathy. There is a paucity of data concerning posttransplant cardiac complications in patients undergoing PT-Cy-based HCT.. A retrospective analysis of 176 patients undergoing HCT with PT-Cy was performed. The overall survival, left ventricular ejection fractions, brain natriuretic peptide levels, and cardiac comorbidities were reviewed. The associations between comorbidities and the onset of heart failure were assessed with a Cox proportional hazards model.. Pretransplant cardiomyopathy was found in 16 patients (9.1%) but had no effect on their posttransplant overall survival. Thirty-five patients (21.9%) developed posttransplant cardiomyopathy, which correlated with increased mortality, but this was not statistically different from the frequency-matched non-PT-Cy cohort. The majority of these cardiomyopathies occurred in the setting of an infectious milieu. An age greater than 60 years and an HCT comorbidity index score equal to or greater than 4 were the only risk factors that correlated with posttransplant cardiomyopathy.. The presence of pretransplant cardiomyopathy does not negatively affect overall survival for patients who undergo HCT with PT-Cy. Furthermore, cardiomyopathy in PT-Cy patients is not caused by PT-Cy but is mostly concurrent with infectious complications and is associated with reduced overall survival. Traditional cardiovascular risk factors do not fully predict the occurrence of posttransplant cardiomyopathy. Future research is required to unravel predictive factors for cardiomyopathy after PT-Cy-based HCT. Cancer 2017;123:1800-1809. © 2017 American Cancer Society.

Topics: Adult; Aged; Anemia, Aplastic; Antineoplastic Agents, Alkylating; Bone Marrow Diseases; Cardiomyopathies; Cardiovascular Diseases; Comorbidity; Cyclophosphamide; Echocardiography; Female; Heart Failure; Hematopoietic Stem Cell Transplantation; Humans; Leukemia; Lymphoma; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Myeloproliferative Disorders; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Retrospective Studies; Stroke Volume; Survival Rate; Transplantation Conditioning; Young Adult

The risk of adverse events in patients with left ventricular non-compaction cardiomyopathy (LVNC) is substantial. This study was designed to determine the prognostic value of NT-proBNP, left ventricular ejection fraction (LVEF), NYHA class, and exercise capacity in LVNC patients.. Cox regression analyses were performed for evaluating the prognostic value of NT-proBNP, LVEF, NYHA class, and exercise capacity on the occurrence of death or heart transplantation. 153 patients were included.. During 1013 person-years (longest follow-up 18.5years) 23 patients (15%) died or underwent heart transplantation. We observed a significant relationship of NT-proBNP (adjusted HR 2.44, 95% CI 1.45-4.09, for every NT-proBNP doubling, p=0.0007) and LVEF (adjusted HR for age 60years: 2.68, 95% CI 1.62-4.41, p=0.0001) with the risk of death or heart transplantation. Combined covariate analysis indicated a strong influence of NT-proBNP (adjusted 2.89, 95% CI 1.33-6.26, p=0.007), whereas LVEF was no longer significant (adjusted HR 0.82, 95% CI 0.42-1.67, p=0.66) demonstrating a favorable prognostic power of NT-proBNP over LVEF. An increase in NYHA class was associated with a worse outcome, and exercise capacity revealed a trend in the same direction. For all the abovementioned analyses, similar results were obtained when assessing the values at first presentation.. This study provides evidence that an increase in NT-proBNP is a strong predictor of outcome in patients with LVNC. The prognostic power of NT-proBNP is at least as good as that of LVEF, indicating that routine NT-proBNP measurement may improve risk assessment in LVNC.

Topics: Adult; Biomarkers; Cardiomyopathies; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Cardiac involvement by light-chain (AL) amyloid occurs in up to 50% of patients with primary AL amyloidosis. The prognosis of amyloid heart disease is poor with 1-year survival rates of 35 to 40%. Historically, heart transplantation was considered controversial for patients with AL amyloid cardiomyopathy (CM) given the systemic nature of the disease and poor survival. We present a case report of an active duty service member diagnosed with advanced cardiac amyloid who underwent total artificial heart transplant as a bridge to heart transplant and eventual autologous stem cell transplant.. A 47-year-old active duty male initially evaluated for atypical chest pain was found to have severe concentric left ventricular hypertrophy on echocardiogram but normal voltage on electrocardiogram. Cardiac magnetic resonance imaging, laboratory studies, and bone marrow biopsy established the diagnosis of cardiac amyloidosis. At the time of diagnosis, the patient's prognosis was very poor with a median survival of 5 months on the basis of the Mayo Clinic revised prognostic staging system for amyloidosis. The patient developed rapidly progressive left ventricular dysfunction and heart failure leading to cardiac arrest. The patient received a total artificial heart as a bridge to orthotopic heart and kidney transplantation and eventual stem cell transplant. He continues to be in remission and has a fair functional capacity without restriction in activities of daily living or moderate exercise.. Amyloid CM is a rare and devastating disease. The natural course of the disease has made heart transplant in these patients controversial. Modern advancements in chemotherapies and advanced heart failure treatments have improved outcomes for select patients with AL amyloid CM undergoing heart transplantation. There is ongoing research seeking improvement in treatment options and outcomes for patients with this deadly disease.

Topics: Amyloidosis; Anti-Inflammatory Agents; Bortezomib; Cardiomyopathies; Cyclophosphamide; Dexamethasone; Heart Failure; Heart Transplantation; Heart, Artificial; Humans; Immunosuppressive Agents; Male; Middle Aged; Military Personnel; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Heart failure in pregnancy is rare, but usually ascribed to peripartum cardiomyopathy in the absence of other possible diagnoses. However, heart failure can develop solely due to a tachycardia, so-called 'tachycardia-induced cardiomyopathy'. The incidence of tachycardia-induced cardiomyopathy in pregnancy is unknown, but it is a treatable and potentially reversible cause of heart failure. Clinically, tachycardia-induced cardiomyopathy during pregnancy might present in a similar manner, but its management has to be individualized according to the arrhythmic substrate and usually involve multidisciplinary input from specialists in obstetrics, cardiac electrophysiology and heart failure.

Topics: Adult; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Complications, Cardiovascular; Tachycardia; Ventricular Function, Left

Patients with myocarditis and left ventricular (LV) dysfunction may improve after standard heart failure therapy. This improvement seems to be related to retreat of myocardial inflammation. The aim of the present study was to assess changes in clinical, echocardiographic and some laboratory parameters and to correlate them with changes in the number of inflammatory infiltrating cells in endomyocardial biopsy (EMB) samples during the 6-month follow-up, and to define predictors of LV function improvement among baseline parameters. Forty patients with biopsy-proven myocarditis and impaired LV function (LV ejection fraction-LVEF <40 %) with heart failure symptoms ≤ 6 months were evaluated. Myocarditis was defined as the presence of >14 mononuclear leukocytes/mm(2) and/or >7 T-lymphocytes/mm(2) in the baseline EMB. The EMB, echocardiography and clinical evaluation were repeated after 6 months of standard heart failure therapy. LVEF improved on average from 25 ± 9 to 42 ± 12 % (p < 0.001); LV end-systolic volume and LV end-diastolic volume (LVEDV) decreased from 158 ± 61 to 111 ± 58 ml and from 211 ± 69 to 178 ± 63 ml (both p < 0.001). NYHA class decreased from 2.6 ± 0.5 to 1.6 ± 0.6 (p < 0.001) and NTproBNP from 2892 ± 3227 to 851 ± 1835 µg/ml (p < 0.001). A decrease in the number of infiltrating leukocytes (CD45+/LCA+) from 23 ± 15 to 13 ± 8 cells/mm(2) and in the number of infiltrating T lymphocytes (CD3+) from 7 ± 5 to 4 ± 3 cells/mm(2) (both p < 0.001) was observed. The decline in the number of infiltrating CD45+ cells significantly correlated with the change in LVEF (R = -0.43; p = 0.006), LVEDV (R = 0.39; p = 0.012), NYHA classification (R = 0.35; p = 0.025), and NTproBNP (R = 0.33; p = 0.045). The decrease in the number of CD3+ cells correlated with the change of systolic and diastolic diameters of the left ventricle (R = -0.33; p = 0.038 and R = -0.45; p = 0.003) and with the change in LVEDV (R = -0.43; p = 0.006). Tricuspid annular plane systolic excursion (TAPSE) (OR 0.61; p = 0.005) and early transmitral diastolic flow velocity (E wave) (OR 0.89; p = 0.002) were identified as predictors of LVEF improvement. Improvements in clinical status, LV function and NTproBNP levels correlated with decrease in the number of infiltrating inflammatory cells. TAPSE and E wave velocity were significant predictors of improvement in multivariate regression. Our observations suggest that contemporary guidelines-based therapy of heart failure is an effective treatment

Topics: Adult; Biomarkers; Biopsy; Cardiomyopathies; Cardiovascular Agents; Chemotaxis, Leukocyte; Echocardiography, Doppler; Female; Heart Failure; Humans; Male; Middle Aged; Multivariate Analysis; Myocarditis; Myocardium; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Predictive Value of Tests; Recovery of Function; Risk Factors; Stroke Volume; T-Lymphocytes; Time Factors; Treatment Outcome; Ventricular Dysfunction, Left; Ventricular Function, Left

Several studies suggest that the N-terminal fragment of pro-brain natriuretic peptide levels are quite different in wild-type transthyretin (TTR)-related amyloidosis (ATTRwt) and mutated TTR-related amyloidosis (ATTRm) compared with immunoglobulin light-chain cardiac amyloidosis. Our aim was to test this hypothesis in a cohort of patients with different types of cardiac amyloidosis.. Seventy patients with ATTRwt, ATTRm, and light-chain cardiac amyloidosis matched for left ventricular (LV) mass index were studied by standard echocardiography, tissue Doppler imaging, and plasmatic cardiac biomarkers.. Despite similar LV mass and renal function, patients with ATTR cardiac amyloidosis showed lower levels of N-terminal fragment of pro-brain natriuretic peptide than do light-chain amyloidosis ones, especially when expressed as a function of LV mass index.. Amyloidogenic light-chain-derived fibrils induce more severe myocardial dysfunction in light-chain amyloidosis than in ATTR, despite similar myocardial infiltration. Thus, the degree of cardiac dysfunction may be related not only to the amount of amyloid deposited, but also to qualitative differences among fibrils.

Topics: Aged; Aged, 80 and over; Amyloidosis; Biomarkers; Cardiomyopathies; Echocardiography, Doppler; Female; Heart; Humans; Immunoglobulin Light Chains; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prealbumin; Retrospective Studies; Ventricular Function, Left

Cardiac involvement is the most important prognostic factor in eosinophilic granulomatosis with polyangiitis (EGPA, Churg-Strauss syndrome). The aims of this study were to describe findings of cardiac magnetic resonance (CMR) in patients with active EGPA and to find factors associated with cardiac involvement detected by CMR that could help identify patients who would benefit from the examination. Medical records and CMR images in 16 consecutive EGPA patients (8 women and 8 men, median age of 47 years ranging from 34 to 68 years) were reviewed. Clinical features and results of laboratory tests were compared according to the presence of myocardial late gadolinium enhancement (LGE) on CMR images. The patients were followed for the development of cardiac symptoms and signs (mean follow up duration, 40.5 ± 12.8 months). Among the total of 16 patients, 8 (50 %) had myocardial LGE according to CMR, located in the subendocardial layer in 7 of them (87.5 %). The extent of LGE had a significant negative correlation with left ventricular ejection fraction (LVEF, ρ = -0.723, p = 0.043). The presence of LGE was associated with larger end-systolic left ventricle internal dimension (34 vs. 28 mm, p = 0.027) and presence of diastolic dysfunction (75 vs. 0 %, p = 0.008) on echocardiography, elevated NT-proBNP (75 vs. 12.5 %, p = 0.012), and elevated CK-MB (62.5 vs. 0 %, p = 0.010) compared to the group without LGE. Only one patient (6.3 %) had cardiac symptoms before CMR and another patient (6.3 %) developed heart failure 4 years later during remission. The other 14 patients remained free from cardiac signs and symptoms during the follow-up period. In patients with active EGPA, CMR enables detection of cardiac involvement when cardiac symptoms are not present. Echocardiographic diastolic dysfunction and elevated NT-proBNP or CK-MB may help identify active EGPA patients who can benefit from CMR to detect cardiac involvement without cardiac symptoms.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Churg-Strauss Syndrome; Contrast Media; Creatine Kinase, MB Form; Disease Progression; Disease-Free Survival; Female; Granulomatosis with Polyangiitis; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Organometallic Compounds; Peptide Fragments; Predictive Value of Tests; Retrospective Studies; Stroke Volume; Time Factors; Ventricular Function, Left

Sheng-Mai Yin (SMY), a modern Chinese formula based on Traditional Chinese Medicine theory, has been used to treat cardiovascular diseases in Eastern Asia. Our study focuses on the cardioprotection of SMY against doxorubicin (DOX)-induced cardiac toxicity in vivo.. Rats were injected with DOX (2.5 mg/kg) in six injections over a 2-week period. SMY was administrated intragastrically at the dose of 8.35, 16.7 and 33.4 g/kg, or 16.7 g/kg only twice a day concurrently with DOX for the 2-weeks. A series of assays were performed to detect the effects of SMY on: (i) heart weight index (HWI) and left ventricular mass index (LVMI); (ii) cardiac function; (iii) heart tissue morphology; (iv) the contents of carboxy terminal propeptide of procollagen typeI (PICP), amino terminal propeptide of procollagen type III (PШNP), transforming growth factor-β1 (TGF-β1), B-type natriuretic peptide (BNP), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (INF-γ) and interleukin 6 (IL-6) by ELISA; (v) the mRNA levels of TGF-β1 and toll-like receptor-2 (TLR2); and (vi) protein level of TGF-β1.. Rats treated with SMY displayed the reductions of BNP and CK-MB increased by DOX in a dose-dependent manner. Moderate dose of SMY exhibited the correction for the increased HWI, LVMI, and the injured cardiac function, as well as the collagen accumulation. In addition, cardioprotection of SMY against DOX-induced cardiac toxicity was demonstrated by the reduction of myocardial fibrosis, characterized by the suppression of PICP, PШNP and TGF-β1, as well as the anti-inflammation and the regulation for cardiac immune microenvironment, characterized by the inhibition of TLR2, MCP-1, INF-γ and IL-6.. SMY may protect heart function through the restriction of myocardial fibrosis induced by DOX, which suggests the potentially therapeutic effect of SMY on DOX-induced cardiomyopathy.

Topics: Animals; Cardiomyopathies; Cardiotonic Agents; Cardiotoxicity; Creatine Kinase, MB Form; Disease Models, Animal; Doxorubicin; Drug Combinations; Drugs, Chinese Herbal; Heart; Inflammation Mediators; Male; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Wistar

Topics: Aged; Amyloidosis; Cardiomyopathies; Creatine Kinase; Diphosphonates; Humans; Male; Middle Aged; Muscle, Skeletal; Natriuretic Peptide, Brain; Organotechnetium Compounds; Peptide Fragments; Radionuclide Imaging; Serum Amyloid P-Component; Survival Analysis; Troponin

We investigated whether urinary 8-hydroxy-2'-deoxyguanosine (U-8-OHdG), a marker of oxidative DNA damage, is a prognosticator of cardiovascular-related death in patients with cardiac sarcoidosis (CS).. In this prospective study, 30 consecutive patients were divided into the active CS (n=20) and non-active CS (n=10) groups, based on abnormal isotope accumulation in the heart on (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography ((18)F-FDG PET/CT) imaging. Nineteen patients in the active CS group underwent corticosteroid therapy. Before corticosteroid therapy initiation, U-8-OHdG, brain natriuretic peptide (BNP), other biomarkers, and indices of cardiac function were measured. Patients were followed-up for a median of 48months. The primary endpoint was the incidence of cardiovascular-related death. During the follow-up period, in the corticosteroid-treated active CS group, 7 of 19 patients experienced cardiovascular-related death. By contrast, in the non-active CS group, 1 of 10 patients died from cardiovascular-related causes. Univariate and multivariate analyses showed that U-8-OHdG and BNP were independent predictors for cardiovascular-related death. The cut-off values for predicting cardiovascular death in corticosteroid-treated patients with active CS were 19.1ng/mg·Cr and 209pg/mL for U-8-OHdG and BNP, respectively. Patients with a U-8-OHdG concentration ≥19.1ng/mg·Cr or a BNP concentration ≥209pg/mL had a significantly higher cardiovascular-related death risk, but U-8-OHdG had better predictive value compared with BNP.. These findings suggested that U-8-OHdG was a powerful predictor of cardiovascular-related death in patients with CS, suggesting that active CS patients with elevated U-8-OHdG levels might be resistant to corticosteroid therapy.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Adrenal Cortex Hormones; Adult; Aged; Biomarkers; Cardiomyopathies; Deoxyguanosine; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Sarcoidosis; Survival Analysis; Treatment Outcome

Diabetic cardiomyopathy (DCM) is one of the most common causes of mortality. Its pathophysiology is not fully understood and involve number of factors including, cardiovascular and metabolic disorders. The present study was designed to study the pathogenesis of DCM and to explore the effects of levosimendan along with either ramipril or insulin in the long term management of DCM.. Streptozotocin (STZ) was used to develop DCM in Wistar rats at the dose of 25mg/kg body weight for three consecutive days. Rats were randomly divided into 9 groups and treatments were started after 2weeks of STZ administration.. Persistent hyperglycemia was observed in STZ treated rats, leading to significant contractile dysfunction as evidenced by decreased left ventricular pressure (LVP), +LV (dp/dt), -LV (dp/dt) as well as elevated Tau and LVEDP. Marked myocardial damage such as fibrosis, increased wall tension, depletion of contractile proteins were observed as evidenced by increased levels of TGF-β, BNP, cTroponin-I, as well as decreased expression of SERCA2a and NCX1 proteins in diabetic rats. The levosimendan alone and also in combination with either ramipril or insulin significantly normalized the myocardial dysfunctions developed during the course of persistent hyperglycemia.. The study suggests that levosimendan treatment improves cardiac dysfunction significantly. Its combined use with ramipril proves better than with insulin in correcting myocardial performance as well as reduction in myocardial damage.

Topics: Animals; Body Weight; Cardiomyopathies; Cardiotonic Agents; Diabetes Mellitus, Experimental; Heart; Hemodynamics; Hydrazones; Male; Natriuretic Peptide, Brain; Nitric Oxide; Pyridazines; Rats; Rats, Wistar; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Simendan; Sodium-Calcium Exchanger; Streptozocin; Transforming Growth Factor beta; Troponin I

Cardiac disease accounts for a large burden of premature mortality and morbidity in patients with type 1 myotonic dystrophy (MD). However, little is known about structural cardiac abnormalities particularly in asymptomatic patients with MD. We sought to describe the prevalence and extent of structural cardiac abnormalities in patients with MD and to assess their association with functional, electrical, biochemical and genetic disturbances.. In this case-control study, 40 adults with MD who had no contraindications to cardiac MRI (CMR) were identified from the Grampian region genetic database. Forty-one age-and-gender-matched healthy volunteers were also recruited. All subjects underwent detailed assessment including CMR, echocardiography, electrocardiography, signal-averaged electrocardiography, Holter monitoring and quantification of serum B-type natriuretic peptide (BNP). Genetic testing of patients with MD was performed with quantification of CTG trinucleotide repeat sequences. Results of clinical, electrical, genetic and biochemical investigations were correlated with cardiac structural and functional abnormalities detected on CMR.. Electrical disturbances including prolongation of PR (187±29 vs 156±23 ms, p<0.001) and QRS intervals (99±11 vs 89±9 ms, p<0.001) were the most prevalent abnormality. Patients with MD had a significantly lower left ventricular (LV) mass (142±44 vs 172±73 g, p=0.03) and lower right ventricular (RV) ejection fraction (46±9 vs 50±7%, p=0.02) compared with controls, although LV ejection fraction was similar between the groups (58±8 vs 59±6%, p=0.34). LV non-compaction was also significantly more prevalent in the MD cohort (35% vs 12%, p=0.019). Late gadolinium enhancement was present in 13% of patients with MD. Muscular disability scores correlated with electrical changes (r=0.529, p<0.001); however, the number of CTG repeat sequences did not correlate with either electrical or structural abnormalities.. Patients with MD have a high prevalence of both electrical and structural abnormalities. These include reduced LV mass, impaired RV contractility, a high prevalence of LV non-compaction and myocardial fibrosis. These findings illustrate the potential utility of CMR detecting subclinical disease in otherwise asymptomatic patients with MD.

Topics: Action Potentials; Adult; Arrhythmias, Cardiac; Asymptomatic Diseases; Biomarkers; Cardiomyopathies; Case-Control Studies; Echocardiography, Doppler; Electrocardiography, Ambulatory; Female; Fibrosis; Heart Conduction System; Heart Rate; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Myotonic Dystrophy; Natriuretic Peptide, Brain; Prevalence; Prognosis; Risk Factors; Scotland; Stroke Volume; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling

This study aimed to evaluate the predictive and prognostic value of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in patients with myocardial dysfunction induced by severe sepsis and septic shock.. A total of 84 patients with severe sepsis and septic shock were enrolled between May 2013 and December 2014.The patients were monitored by pulse indicator continuous cardiac output system and divided into myocardial depression group (cardiac function index [CFI] < 4.1/minute, n = 37) and nonmyocardial depression group (CFI ≥ 4.1/minute, n = 47 ). Additionally, the patients were divided into survival group (n = 40) and nonsurvival group (n = 44) based on 28-day mortality. Hemodynamic parameters and serum sTREM-1, B-type natriuretic peptide (BNP) and cardiac troponin I (cTnI) levels were collected on days 1, 3 and 5 after admission to intensive care unit.. (1) The serum values of sTREM-1, BNP and cTnI in myocardial depression group were higher than those in nonmyocardial depression group (P < 0.01); and CFI, cardiac index, stroke volume, global ejection fraction and left ventricular contractility index (dpmax) in myocardial depression group were lower than those in nonmyocardial depression group on day 1 (P < 0.05); (2) serum sTREM-1 negatively correlated with left ventricular ejection fraction, CFI, cardiac index, global ejection fraction and dpmax, and it positively correlated with BNP and cTnI (P < 0.01); (3) the area under the receiver operating characteristics curve for sTREM-1 in the prediction of myocardial depression was 0.671 with a sensitivity of 83.8% and a specificity of 46.8% when cutoff point was 174.5ng/mL, the power of predicting septic depression for sTREM-1 was lower than that of BNP; logistic regression analysis showed that serum sTREM-1 was not an independent predictor of septic myocardial depression; the area under the receiver operating characteristics curve was 0.773 for sTREM-1 in predicting outcome with a sensitivity of 86.4% and a specificity of 80% when cutoff point was 182.3ng/mL, the power of predicting prognosis for sTREM-1 was superior to those of BNP and cTnI; (4) there was a decrease trend for sTREM-1 levels and an increasing trend for CFI in the survival group (P < 0.05).. Myocardial dysfunction is common in patients with severe sepsis and septic shock and high serum levels of sTREM-1 correlates with myocardial dysfunction to some extent but is not an independent predictor, which more importantly showed prognostic value for septic shock outcome.

Topics: Adult; Aged; Aged, 80 and over; Cardiac Output; Cardiomyopathies; Echocardiography; Female; Heart; Humans; Male; Membrane Glycoproteins; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Receptors, Immunologic; ROC Curve; Sepsis; Shock, Septic; Stroke Volume; Triggering Receptor Expressed on Myeloid Cells-1; Troponin I

High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression.. For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] %; follow-up, 3.2 [2.3-4.9] %; P<0.001) and slightly elevated hs-TNT (baseline, 44.7 [30.1-65.3] ng/L; follow-up, 49.1 [27.6-69.5] ng/L; P=0.116) during follow-up. Left ventricular wall thickness and EF of patients with elevated hs-TNT were decreased during follow-up, indicating potential cardiomyopathy progression.. hs-TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients.

Topics: Adult; Analysis of Variance; Biomarkers; Cardiomyopathies; Disease Progression; Echocardiography; Fabry Disease; Female; Fibrosis; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Angiography; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Retrospective Studies; Troponin

To investigate the effects of renal denervation (RDN) on comprehensive cardiac and renal fibrosis in cardiomyopathy. Five weeks after successful transverse aortic constriction (TAC)-induced cardiomyopathy model building, Sprague-Dawley rats were randomly assigned to three groups: (1) RDN, (2) sham, and (3) losartan. Sham TAC rats served as control group. Compared with control, TAC groups showed a significant decrease in left ventricle ejection fraction and increase in ventricular septum thickness and left atrium diameter on echocardiography after 5 weeks. At 10 weeks post-TAC, venous blood samples were collected for fibrosis biochemical assay. Heart and kidney samples were also harvested for fibrosis pathophysiological detection. Cardiac and renal fibrosis quantity results showed that, compared with sham group, collagen volume fraction was significantly decreased in RDN group more than in losartan group. Biochemical parameters such as tumor necrosis factor α, aldosterone, and B-type natriuretic peptide levels as well as biomarkers for fibrosis such as procollagen type I N-terminal propeptide and procollagen type III N-terminal propeptide concentrations were significantly decreased in RDN group in comparison with sham. In addition, compared with sham group, left ventricle tissue protein expression of transforming growth factor-β1 and angiotensin II type I receptor was downregulated, and angiotensin-converting enzyme 2 was upregulated in RDN but not in losartan group. RDN significantly attenuates cardiac and renal fibrosis in cardiomyopathy. Differing from losartan, which only has angiotensin II type I receptor inhibition effects, RDN comprehensively suppresses cardiac and renal fibrogenesis through multiple pathways.

Topics: Aldosterone; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Biomarkers; Cardiomyopathies; Disease Models, Animal; Fibrosis; Heart Atria; Heart Ventricles; Humans; Kidney; Losartan; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Rats; Rats, Sprague-Dawley; Renin-Angiotensin System; Sympathectomy

Right ventricular (RV) dysfunction is a strong predictor of poor outcomes in heart failure. Its prognostic meaning in cardiac amyloidosis (CA) is under-investigated.. Hundred and twenty nine patients with suspected CA and an interventricular septum thickness (IVST) ≥ 12 mm underwent echocardiography with measurement of left ventricular (LV) and RV longitudinal strain (LS), late gadolinium-enhancement (LGE) cardiac MRI, and standard evaluation.. Among 82 confirmed CA, types were immunoglobulin light chain (AL, n = 26), hereditary transthyretin (m-TTR, n = 37) and senile (WT-TTR, n = 19). Compared to those without, CA patients had significantly lower RV fractional shortening (RV-FS), tricuspid annular plane systolic excursion (TAPSE), tissue Doppler systolic velocity, and global RV-LS, without any difference among the CA types. RV-LGE, observed in 62% of CA patients, was associated with lower global and basal RV-FS. Median follow-up was 8(2; 16) months. Using multivariate analysis, NYHA-class and low TAPSE independently predicted major adverse cardiac event (MACE) defined as death, heart transplantation and acute heart failure. Independent determinants of TAPSE < 14 mm, the best cut-off value, were LV ejection fraction (LVEF), estimated filling pressure (E/E'), NT-proBNP and pulmonary artery pressure, but not RV-LGE.. RV dysfunction is common in CA. Its routine evaluation by a simple TAPSE may be an aid in assessing the prognosis of CA patients.

Topics: Aged; Aged, 80 and over; Amyloidosis; Cardiomyopathies; Echocardiography, Doppler; Female; Heart Failure; Heart Transplantation; Heart Ventricles; Humans; Immunoglobulin Light Chains; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prealbumin; Prognosis; Prospective Studies; Stroke Volume; Survival Analysis; Ventricular Dysfunction, Right

Cirrhotic cardiomyopathy (CCM) is defined as an abnormal heart structure and function in cirrhotic patients. CCM includes systolic and diastolic dysfunction, electrophysiological abnormalities, and structural changes, both microscopic and macroscopic. Currently, there is no one diagnostic test that can identify patients with CCM. Evaluation of the validity of galactin-3 and brain natriuretic peptide (BNP) as biomarkers in the early detection of CCM in comparison to conventional echocardiography.. A case control study was carried out in the Departments of internal medicine and tropical Medicine, Assuit University, Egypt. Seventy-one subjects were divided into the following three groups: 26 cirrhotic patients without ascites, 25 cirrhotic patients with ascites, and 20 healthy controls. All groups underwent clinical examination, and laboratory investigation including BNP, galactin-3, and echocardiography.. There was a significant difference between the three groups (p < 0.001) with regard to corrected QT (cQT), BNP and galactin-3. Left ventricular diastolic dysfunction with different grades was the most recorded cardiac abnormality in the patient group I and II (88.5% and 96%; respectively) with significantly increased frequency and severity in ascetic patients and with the advancement of liver cirrhosis. BNP and galactin-3 were sensitive and specific biomarkers for the detection of diastolic dysfunction in cirrhotic patients (77.6%, 95.5%, 89.9% and 86.4%; respectively).. Diastolic dysfunction is a common cardiac abnormality in cirrhotic patients that worsens with the advancement of cirrhosis. BNP and galactin-3 had higher sensitivity and specificity in the early detection of CCM compared with those of conventional echocardiography.

Topics: Adult; Biomarkers; Cardiomyopathies; Case-Control Studies; Early Diagnosis; Echocardiography; Egypt; Female; Galectin 3; Humans; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Sensitivity and Specificity; Ventricular Dysfunction, Left

Natriuretic peptide (NP) levels are routinely employed as useful diagnostic and prognostic tools in the evaluation of patients with heart failure (HF). As hospitalization is the major consumer of healthcare resources, the prognostic power of admission NPs with regard to the duration of hospitalization deserves further investigation.. We assessed retrospectively the association between NP values sampled shortly following unplanned admission and the duration of hospitalization in 2978 patients admitted to a cardiology department. Duration of hospitalization (hours) and survival were determined by interrogation of the electronic medical records system. Associations with peptide levels were estimated using regression models and receiver operating characteristic (ROC) analysis. The results demonstrate a significant positive relationship between NP levels and the duration of hospitalization, after adjusting for age (P < 0.001). The median duration of hospitalization for the lowest BNP and NT-proBNP quintiles were 80 and 97 h, respectively, vs. 224.5 and 236 h for the highest quintiles. Using cut-off levels of 115 pmol/L for BNP and 390 pmol/L for NT-proBNP, the peptides have a positive predictive value of 78% and 85% for a stay >4 days. During follow-up, NP levels were strongly predictive of all-cause mortality.. The results quantify the strong relationship between NP levels taken following an unplanned admission to a cardiology department and the duration of hospitalization. This information permits improved identification of a patient population likely to require a prolonged hospital stay and consume more healthcare resources. Such patients may require a more aggressive diagnostic, treatment, and management strategy.

Topics: Aged; Arrhythmias, Cardiac; Cardiology Service, Hospital; Cardiomyopathies; Female; Heart Failure; Hospitalization; Hospitals, University; Humans; Hypertension; Length of Stay; Linear Models; Male; Middle Aged; Mortality; Myocardial Ischemia; Natriuretic Peptide, Brain; Norway; Peptide Fragments; Proportional Hazards Models; Respiratory Tract Infections; Retrospective Studies; ROC Curve

Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking-derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

Topics: Aged; Biomarkers; Biopsy; Cardiomyopathies; Contrast Media; Electrocardiography; Female; Fibrosis; Gadolinium; Galectin 3; Heart; Humans; Kidney Failure, Chronic; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Renal Dialysis; Troponin T

To evaluate the prognostic value of combination of plasma brain natriuretic peptide(BNP) with the ratio of early diastolic mitral inflow velocity to early diastolic mitral annulus velocity(E/E') in the patients with septic shock.. From June 2012 to December 2013 , 127 patients with septic shock were consecutively recruited and underwent trans-thoracic echocardiography examination within 6 h after admission to Intensive Care Unit(ICU), Zhejiang Provincial People's Hospital. Plasma BNP concentration was measured using ELISA method. All Clinical, laboratory, and survival data were prospectively collected.. Of 127 patients enrolled, mean values for age were(59.9±17.3) years and APACHE Ⅱ score(16.8±5.8), respectively. 95 patients(74.8%) took mechanical ventilation. 28- , 60-day mortality rate was 36.3% and 42.3%, respectively. Univariate Cox regression analysis showed that age, coronary artery disease, serum creatinine and lactate, plasma BNP, left ventricular ejection fraction(LVEF), E/E' and APACHE Ⅱ score were significantly(P≤0.05) associated with 60-day mortality. Multivariate analysis revealed that serum lactate, plasma BNP(χ(2)=9.4, P=0.002) , E/E'(χ(2)=4.89, P=0.02) and APACHE Ⅱ score(χ(2)=10.6, P=0.001) remained independent predictors for 60-day mortality. ROC curve analysis showed that the optimal plasma BNP and E/E' cutoff values identified were 338.8 pg/ml and 10.8, and the areas under ROC curve were 0.89(sensitivity: 83.7%; specificity: 81.4%)and 0.83(sensitivity: 76.7%; specificity: 72.9%)for 60-day mortality, respectively. In addition to plasma BNP and clinical predictors, the E/E' could provide in independent and incremental prognostic value of 60-day mortality(χ(2)=59.3 vs 47.8, P<0.001).. Plasma BNP and E/E' are independent predictors for 60-day mortality, and combination of plasma BNP and E/E' could improve risk stratification in patients with septic shock.

Topics: Cardiomyopathies; Echocardiography; Humans; Intensive Care Units; Middle Aged; Mitral Valve; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; ROC Curve; Shock, Septic; Ventricular Function, Left

The prognosis of amyloidosis is known to depend heavily on cardiac function and may be improved by identifying patients at highest risk for adverse cardiac events.. Identify predictors of mortality in patients with cardiac light-chain amyloidosis (AL), hereditary transthyretin amyloidosis (m-TTR), or wild-type transthyretin amyloidosis (WT-TTR) to prompt physician to refer these patients to dedicated centers.. Observational study. About 266 patients referred for suspected cardiac amyloidosis (CA) in two French university centers were included. About 198 patients had CA (AL = 118, m-TTR = 57, and WT-TTR = 23). Their median (25th-75th percentile) age, NT-proBNP left ventricular ejection fraction were, respectively, 68 years (59-76), 2339 pg mL. NT-proBNP is a strong prognosticator in the three types of cardiac amyloidosis. High NT-proBNP, low cardiac output, and pericardial effusion at the time of screening should prompt physician to refer the patients to amyloidosis referral center.

Topics: Aged; Aged, 80 and over; Amyloidosis; Biomarkers; Cardiac Output, Low; Cardiomyopathies; Female; Follow-Up Studies; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pericardial Effusion; Prealbumin; Prognosis; Stroke Volume; Survival Analysis; Ventricular Function, Left

Hypocalcemic cardiomyopathy is a rare entity. We describe a patient with severe heart failure, decreased ejection fraction and global hypokinesia documented on echocardiogram, associated with severe hypocalcemia, very low vitamin D status, increased QT intervals, increased BNP (serum brain natriuretic peptide) levels and CPK (creatine phosphokinase) levels. All these defects reversed on treatment with vitamin D and calcium within a few days without any specific cardiac intervention.

Topics: Aged; Calcium; Cardiomyopathies; Creatine Kinase; Echocardiography; Heart Failure; Humans; Hypocalcemia; Hypokinesia; Natriuretic Peptide, Brain; Pseudohypoparathyroidism; Treatment Outcome; Vitamin D; Vitamin D Deficiency; Vitamins

Topics: Adult; Cardiomyopathies; Electrocardiography; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Tachycardia

To investigate the effects of renal denervation (RDN) on multi-organ fibrosis and vascular remodeling in cardiomyopathy.. Thirty-six male Sprague-Dawley rats underwent transverse aortic constriction (TAC). Five weeks later, 28 surviving TAC rats were randomly assigned to three groups: (1) RDN, (2) Sham, (3) Carvedilol. Six male Sham TAC rats served as the Control. Ten weeks after TAC, samples were collected.. TAC rats showed an increased diastolic interventricular septal thickness at week 5. At 10 weeks, Masson staining showed that left ventricular and renal glomerular fibrosis were significantly reduced in RDN compared with Sham group. In comparison to Sham group, hepatic perivascular fibrosis was attenuated in both RDN and Carvedilol group, so were the media thickness and the media/lumen of aorta. The plasma levels of B-type natriuretic peptide (BNP), Cystatin C (Cys-C), Alanine Transaminase, angiotensin II (Ang II), transforming growth factor beta 1 (TGF-β1), and malondialdehyde increased, and total superoxide dismutase (T-SOD) decreased in Sham but not in RDN group, compared with Control group. Both RDN and Carvedilol reduced the Cys-C and TGF-β1 levels, and restored T-SOD concentration, compared with Sham group. While only RDN lowered the plasma levels of BNP and Ang II. No significant effects of RDN on blood pressure (BP) and heart rate (HR) were oberved.. RDN can attenuate multi-organ fibrosis and improve vascular remodeling independent of BP and HR change in TAC-induced cardiomyopathy. These effects of RDN may be associated with the direct inhibition of renin-angiotensin-aldosterone system and oxidative stress.

Topics: Alanine Transaminase; Angiotensin II; Animals; Aorta; Blood Pressure; Carbazoles; Cardiomegaly; Cardiomyopathies; Carvedilol; Constriction; Cystatin C; Denervation; Fibrosis; Heart Rate; Kidney; Malondialdehyde; Natriuretic Peptide, Brain; Organ Specificity; Oxidative Stress; Peptide Fragments; Procollagen; Propanolamines; Rats, Sprague-Dawley; Superoxide Dismutase; Transforming Growth Factor beta1; Vascular Remodeling

Cardiac involvement in systemic sclerosis (SSc) is considerably frequent in autopsy, but the early identification is clinically difficult. Recent advantages in cardiac magnetic resonance (CMR) enabled to detect myocardial fibrotic scar as late gadolinium enhancement (LGE). We aimed to examine the prevalence and distribution of LGE in patients with SSc, and associate them with clinical features, electrocardiographic abnormalities and cardiac function. Forty patients with SSc (58 ± 14 years-old, 35 females, limited/diffuse 25/15, disease duration 106 ± 113 months) underwent serological tests, 12-lead electrocardiogram (ECG) and CMR. Seven patients (17.5 %) showed LGE in 26 segments of left ventricle (LV). LGE distributed mainly in the basal to mid inter-ventricular septum and the right ventricular (RV) insertion points, but involved all the myocardial regions. More patients with LGE showed NYHA functional class II and more (71 vs. 21 %, p < 0.05), bundle branch blocks (57 vs. 6 %, p < 0.05), LV ejection fraction (LVEF) < 50 % (72 vs. 6 %, p < 0.01), LV asynergy (43 vs. 0 %, p < 0.01) and RVEF < 40 % (100 vs. 39 %, p < 0.01). There was no difference in disease duration, disease types, or prevalence of positive autoimmune antibodies or high serum NT-proBNP level (>125 pg/ml). When cardiac involvement of SSc was defined as low LVEF, ECG abnormalities or high NT-proBNP, the sensitivity, specificity positive and negative predictive values of LGE were 36, 92, 71 and 72 %, respectively. We could clarify the prevalence and distribution of LGE in Japanese patients with SSc. The presence of LGE was associated with cardiac symptom, conduction disturbance and impaired LV/RV contraction.

Topics: Adolescent; Adult; Aged; Cardiomyopathies; Contrast Media; Electrocardiography; Female; Gadolinium; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Scleroderma, Systemic; Ventricular Function, Left; Young Adult

Few studies have analyzed the clinical and echocardiographic differences between light-chain (AL) and transthyretin (TTR) amyloidosis.. The aim of the present research was to compare, in a real-world setting, the clinical and echocardiographic profiles of these kinds of amyloidosis, at the time of diagnosis, using new-generation echocardiography.. Seventy-nine patients with AL and 48 patients with TTR amyloidosis were studied.. According to the criterion of mean left ventricular (LV) thickness >12 mm, 45 AL (C-AL) and all TTR patients had cardiac amyloidotic involvement, whereas 34 AL patients did not. TTR patients had increased right ventricular (RV) and LV chambers with increased RV and LV wall thickness and reduced LV ejection fraction and fractional shortening. Furthermore, TTR patients showed lower N-terminal pro Brain Natriuretic Peptide concentrations and New York Heart Association functional class when compared with C-AL.. Our data show that at time of first diagnosis, TTR patients have a more advanced amyloidotic involvement of the heart, despite less severe symptoms and biohumoral signs of heart failure. We can hypothesize that we observed different diseases at different stages. In fact, AL amyloidosis is a multiorgan disease with quick progression rate, that becomes rapidly symptomatic, whereas TTR amyloidosis might have a slow progression rate and might remain poorly symptomatic for a greater amount of time.

Topics: Aged; Aged, 80 and over; Amyloid Neuropathies, Familial; Amyloidosis; Biomarkers; Cardiomyopathies; Cross-Sectional Studies; Disease Progression; Echocardiography, Doppler; Female; Humans; Immunoglobulin Light Chains; Male; Middle Aged; Mutation; Natriuretic Peptide, Brain; Peptide Fragments; Prealbumin; Predictive Value of Tests; Severity of Illness Index; Troponin I; Ventricular Function, Left; Ventricular Function, Right

Tissue Doppler imaging (TDI) can identify cardiac dysfunction in adults. This study is aimed to improve early identification of initial left ventricular (LV) dysfunction secondary to ectopic atrial tachycardia (EAT) in children by TDI. A total of 70 children with EAT were included in the present study. Cardiac function was evaluated by conventional echocardiography, TDI, and plasma N-terminal pro-brain natriuretic peptide (NT-proBNP). Doppler signals obtained from the mitral inflow and TDI of the mitral annulus were the average values of three consecutive heartbeats. Left ventricular ejection fraction (LVEF), peak early diastolic transmitral velocity (E), peak systolic mitral annulus velocity (S'), early diastolic mitral annular velocity (E'), the ratio E/E', and TDI-derived myocardial performance index (TDI-MPI) were compared between two groups of children with normal or elevated plasma NT-proBNP concentrations. Of the children, 18.6% demonstrated tachycardia-induced cardiomyopathy (TIC). Compared with LVEF, the TDI-MPI and E/E' showed better correlations with elevated plasma NT-proBNP. Addition of TDI-MPI and E/E' to LVEF provided increased information to detect elevated plasma NT-proBNP (91.67% sensitivity).. TIC occurred in 18.6% of children with EAT. Initial LV dysfunction assessed by the TDI-MPI and E/E' is associated with elevated plasma NT-proBNP, even the LVEF is normal.

Topics: Adolescent; Cardiomyopathies; Child; Early Diagnosis; Echocardiography; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Tachycardia, Ectopic Atrial; Ventricular Dysfunction, Left

We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients.. At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration.. A total of 267 patients (age 66 ± 12 years, males 80%, LVEF 25% ± 8%, ischemic cardiomyopathy 52%, QRSd 155 ± 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48-21.69) and 2.50 (95% confidence interval [CI]: 1.04-6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001).. Among CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH.

Topics: Aged; Biomarkers; Cardiac Resynchronization Therapy; Cardiomyopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Prospective Studies; Surveys and Questionnaires; Survival Analysis; Treatment Outcome; Troponin

Desmin regulates function of mitochondria, T-tubular system and cytosolic Ca(2+) transients. We investigated whether desmin remodeling correlates with diastolic dysfunction and whether progressive desmin abnormalities are accompanied by increasing diastolic dysfunction stages.. Eighty five patients with idiopathic dilated cardiomyopathy and suspected myocarditis without confirmed cardiac tissue inflammation in histopathology assays were included and divided into groups: with preserved EF and reduced EF. After echocardiographic analysis of diastolic dysfunction we identified 2 preserved EF subgroups (normal diastolic function (NDF) and impaired relaxation (IR)) and 3 reduced EF subgroups (NDF, IR, and pseudonormalization). Patients with preserved EF and NDF formed the control group. Tissue desmin staining revealed 4 types of desmin expression: I - normal, with regular pattern of cross-section, IIA - increased with regular pattern, IIB - increased, with irregular pattern and presence of aggregates, III - decreased/lack desmin.. Desmin I was observed only in patients with NDF n=8 (100%) in preserved EF and reduced EF, desmin IIA in NDF n=8 (33%) in preserved EF and n=5 (33%) in reduced EF and IR n=16 (66%) in preserved EF and n=10 (66%) in reduced EF. Desmin IIB and III were observed in patients with reduced EF and diastolic dysfunction: IR and pseudonormalization n=9 (39%) and n=2 (29%); n=14 (61%) and n=5 (71%), respectively. Desmin was found to be an independent predictor of diastolic function parameters β=-0.63, R(2)=0.52 for E'; β=0.54, R(2)=0.42 for E/E'.. Increasing desmin abnormalities were correlated with diastolic dysfunction progression. Desmin expression represents a novel factor contributing or paralleling the development of diastolic dysfunction.

Topics: Adult; Cardiomyopathies; Desmin; Female; Humans; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Remodeling

Restrictive mitral annuloplasty (RMA) can reverse left ventricular (LV) remodeling and reduce plasma B-type natriuretic peptide (BNP), a surrogate biomarker of heart failure. However, the relationship between reverse LV remodeling and plasma BNP changes after RMA is poorly defined. We explored the main hemodynamic factors contributing to change in plasma BNP after RMA in patients with functional mitral regurgitation (MR).. Twenty-four patients with moderate to severe functional MR secondary to LV systolic dysfunction [ejection fraction (EF) <40%] underwent 64-row multidetector computed tomography (MDCT) before and 1.4 months after RMA. LV end-diastolic volume index (EDVI), end-systolic volume index (ESVI), LVEF, and regional and global end-systolic wall stress (ESS) were calculated from 3-dimensional MDCT images, with blood samples for plasma BNP measurement collected the same day.. After RMA, LV volumes and global ESS were decreased, while LVEF improved (all p<0.01). There were significant correlations between changes in LVEDVI and LVESVI (r=0.90, p<0.0001), LVESVI and global ESS (r=0.54, p=0.006), and global ESS and LVEF (r=-0.60, p=0.002). The median value for the plasma BNP also decreased from 597 pg/ml [interquartile range (IQR), 360-934 pg/ml] to 207 pg/ml (IQR, 124-271 pg/ml), in association with changes in LVEDVI (r=0.47, p=0.019), LVESVI (r=0.56, p=0.004), LVEF (r=-0.60, p=0.002), and global ESS (r=0.74, p<0.0001). Multivariate regression analysis showed that global ESS change was the strongest contributor to change in natural-log-transformed plasma BNP (standardized partial regression coefficient=0.59, p=0.004), indicating a strong association between decrease in LV afterload and reduction in plasma BNP level after RMA.. There may be a significant association between LV reverse remodeling and plasma BNP change after RMA. Furthermore, LV end-systolic myocardial stress may be the key mechanical stimulus influencing plasma BNP after surgical correction for functional MR. Whether these favorable BNP responses and reverse remodeling can predict improved survival requires further study.

Topics: Aged; Cardiomyopathies; Female; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Mitral Valve Annuloplasty; Mitral Valve Insufficiency; Multidetector Computed Tomography; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Remodeling

High levels of circulating catecholamines have been established as fundamental pathophysiological elements of heart failure (HF). However, it is unclear whether the increased gene expression of catecholamine-synthesis enzymes in the adrenal glands contributes to these hormone abnormalities in large animal HF models. We analyzed the mRNA levels of catecholamine-synthesizing enzymes: tyrosine hydroxylase (TH), aromatic L-amino acid decarboxylase (AAAD), dopamine-β-hydroxylase (DBH) and phenylethanolamine N-methyltransferase (PNMT) in adrenal glands of 18 pigs with chronic systolic non-ischaemic HF (tachycardia-induced cardiomyopathy due to right ventricle pacing) and 6 sham-operated controls. Pigs with severe HF demonstrated an increased expression of TH and DBH (but neither AAAD nor PNMT) as compared to animals with milder HF and controls (P<0.05 in all cases). The increased adrenal mRNA expression of TH and DBH was accompanied by a reduced left ventricle ejection fraction (LVEF) (P<0.001) and an elevated plasma B-type natriuretic peptide (BNP) (P<0.01), the other indices reflecting HF severity. There was a positive relationship between the increased adrenal mRNA expression of TH and DBH, and the high levels of circulating adrenaline and noradrenaline (all P<0.05). The association with noradrenaline remained significant also when adjusted for LVEF and plasma BNP, suggesting a significant contribution of adrenals to the circulating pool of catecholamines in subjects with systolic HF.

Topics: Adrenal Glands; Animals; Aromatic-L-Amino-Acid Decarboxylases; Cardiomyopathies; Catecholamines; Dopamine beta-Hydroxylase; Epinephrine; Gene Expression; Heart Ventricles; Male; Natriuretic Peptide, Brain; Norepinephrine; Phenylethanolamine N-Methyltransferase; RNA, Messenger; Swine; Tachycardia; Tyrosine 3-Monooxygenase

Topics: Cardiomyopathies; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Tachycardia, Ectopic Atrial; Ventricular Dysfunction, Left

Extrahepatic complications of cirrhosis increase the risk for decompensation of the liver disease and death. Previous studies show common pathogenetic mechanisms involved in the development of hepatopulmonary syndrome and cirrhotic cardiomyopathy. We aimed to assess the link between these entities and their effect on disease-related patient morbidity and mortality.. Seventy-four consecutive cirrhotic patients without prior history of cardiovascular and pulmonary disease were included in a prospective observational study. Routine blood work, arterial blood gas analysis, pulse oximetry measurements, N-terminal pro-brain natriuretic peptide levels and contrast enhanced echocardiography examination with tissue Doppler imaging were performed in all patients. Patients were followed up for a median of 6 months and disease-related adverse events and death were the main outcomes tested. Statistical analysis was conducted according to the presence of hepatopulmonary syndrome or cirrhotic cardiomyopathy.. Hepatopulmonary syndrome was diagnosed in 17 patients (23%) and cirrhotic cardiomyopathy in 30 patients (40.5%). There was no association between the presence of cirrhotic cardiomyopathy and the existence of mild or moderate hepatopulmonary syndrome. No echocardiographic parameters were useful in predicting the presence of hepatopulmonary syndrome. N-terminal pro-brain natriuretic peptide levels and length of QT interval did not aid in diagnosis of cirrhotic cardiomyopathy. Neither entity had significant influence on disease-related outcomes in the follow-up period.. Hepatopulmonary syndrome and cirrhotic cardiomyopathy are independent complications arising in cirrhosis and have a limited influence on morbidity and mortality on a pre-liver transplantation population.

Topics: Aged; Cardiomyopathies; Echocardiography; Female; Follow-Up Studies; Hepatopulmonary Syndrome; Humans; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Romania; Statistics as Topic; Survival Analysis

Chronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF.. We studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (±SD) follow-up period of 4.3±1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4).. Symptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Chi-Square Distribution; Disease Progression; Female; Heart Failure; Hospitalization; Humans; Hypertrophy, Left Ventricular; Incidence; Logistic Models; Male; Middle Aged; Multivariate Analysis; Myocardial Contraction; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Proportional Hazards Models; Prospective Studies; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Surveys and Questionnaires; Time Factors; United States; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

Immunoglobulin light chain (AL) amyloidosis is a systemic disorder caused by depositions of insoluble amyloid fibrils that are composed of fragments of monoclonal light chains produced by abnormal plasma cells. The prognosis is reported to be poor; median survival time (MST) is 1-2 years overall, and is 6 months in patients with cardiac involvement. We here report the treatment outcomes of 24 patients with AL amyloidosis at our hospital between January 2008 and December 2012, including 11 patients with cardiac involvement. MST from the diagnosis was significantly shorter (9.8 months) in patients with cardiac involvement. Of these, patients who achieved a decrease of B-type natriuretic peptide (BNP) to <200 pg/mL after treatment survived longer than patients who did not (MST: not reached vs. 6.1 months; p = 0.003, log-rank test). The median time to decrease BNP to <200 pg/mL was 6.3 months. The decline of BNP to 200 pg/mL or less during treatment predicts longer survival in patients with cardiac AL amyloidosis.

Topics: Adult; Aged; Amyloidosis; Antineoplastic Combined Chemotherapy Protocols; Bortezomib; Cardiomyopathies; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Risk Factors; Survival Analysis; Treatment Outcome

Progressive cardiomyopathy (CMP) is one main cause of death in DMD. This cross-sectional assessment of different cardiac diagnostic procedures focusses on preterm diagnosis of cardiac dysfunction.. 39 male DMD patients aged 6-20 years were included. 6 patients were still ambulatory, 21 patients received corticosteroid therapy.. All patients were investigated by ECG, Holter ECG and heart rate variability (HRV), B-type natriuretic peptide (BNP), echocardiography (TTE), tissue Doppler Imaging (TD) and magnetic resonance imaging (MRI) with Late Gadolinium enhancement (LE) and segmental wall motion analysis (WMA).. 56% of the patients showed repolarization abnormalities and 76% altered HRV. Subnormal ventricular function was found in 25% by TTE and in 34% by MRI. TD differed from normal controls only in the apical septum. In MRI 89% of the patients showed different distribution and intensity of LE and WM restriction. The extent of LE was less in patients after steroid treatment (p<0.05).. MRI with segmental LE- and WM-analysis seems to be superior to TTE and TD in exploring regional distribution and severity of damage of the myocardium. ECG and HRV abnormalities are common in DMD-patients but not tightly predictive for segmental and global left ventricular dysfunction. Targeted treatment of CMP in DMD needs prospective evaluation.. A timely cardiac MRI is the most sensitive investigation for the identification of early myocardial changes in DMD which is a prerequisite for early interventions and therapeutic strategies.

Topics: Adolescent; Autonomic Nervous System Diseases; Cardiomyopathies; Child; Contrast Media; Diagnostic Imaging; Echocardiography, Doppler; Elasticity Imaging Techniques; Electrocardiography; Electrocardiography, Ambulatory; Heart Rate; Hemodynamics; Heterocyclic Compounds; Humans; Magnetic Resonance Imaging; Male; Muscular Dystrophy, Duchenne; Myocardial Contraction; Natriuretic Peptide, Brain; Organometallic Compounds; Reference Values; Young Adult

The B-type natriuretic peptide prohormone (proBNP) is enzymatically cleaved into an inactive N-terminal peptide and a biologically active C-terminal peptide with many beneficial cardiorenal effects. The purpose of this study was to develop and test in cats with cardiomyopathy an immunoassay to quantify the concentrations of C-terminal proBNP in feline plasma. An anti-canine proBNP monoclonal antibody (UI-1021) was shown to have adequate binding affinity to proBNP 80-106 for use in a solid-phase immunoassay, and by epitope mapping to bind within positions 84-87 of feline proBNP. UI-1021 was paired with an affinity-purified rabbit polyclonal detection antibody to feline proBNP 100-106, in a sandwich ELISA with feline proBNP 80-106 standard. The linearity and analytical range and sensitivity of the assay were confirmed from 1.4 to 85 pmol/L. Spike recovery averaged 106.5% (95% confidence interval 78-135%). Within run and intra-assay coefficients of variation were <12%. A protease inhibitor mixture preserved proBNP 80-106 immunoreactivity for at least 5 days in plasma. Clinical verification of the ELISA was done using plasma from 13 cats with cardiomyopathy, whose C-terminal proBNP concentrations ranged from 1.7 to 78.8 pmol/L vs. <1.4-1.8 pmol/L in plasma from 18 healthy cats. Concentrations were found to be substantially lower than reported N-terminal proBNP concentrations, and similar to those of human heart failure patients where relative C-terminal BNP deficiencies have been proposed as contributory to the progression of the disease.

Topics: Animals; Cardiomyopathies; Cat Diseases; Cats; Enzyme-Linked Immunosorbent Assay; Natriuretic Peptide, Brain; Peptide Fragments

Cirrhotic cardiomyopathy has been characterized by impaired contractile response to stress and/or altered diastolic relaxation, with electrophysiological abnormalities in the absence of known cardiac disease. However, the clinical significance of diastolic dysfunction (DDF) in cirrhotic patients has not been clarified.. We studied 84 cirrhotic patients with normal systolic function to evaluate the prevalence of DDF using tissue Doppler imaging, and to investigate the possible correlation of DDF with outcomes (hospitalization, death) and with the specific causes of death.. The mean follow-up was 10±8months. DDF was diagnosed in 22 patients (26.2%). Patients with DDF more frequently had ascites (90.9% vs. 64.5 %; p=0.026), lower levels of albumin (OR: 5.39; p=0.004), higher NT-proBNP levels, and longer QTc interval (464±23ms vs. 452±30ms; p=0.039). At follow-up, patients with DDF did not have a higher incidence of adverse events in terms of hospitalization and death.. The presence of diastolic dysfunction has not been found to be clearly associated with outcome, and prognosis has been determined primarily by the severity of liver disease.

Topics: Adult; Aged; Blood Pressure; Cardiomyopathies; Echocardiography, Doppler; Electrocardiography; Female; Humans; Italy; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain; Outcome Assessment, Health Care; Peptide Fragments; Predictive Value of Tests; Prevalence; Prognosis; Severity of Illness Index; Ventricular Dysfunction, Left

In spite of several research studies help to describe the heart in Fabry disease (FD), the cardiomyopathy is not entirely understood. In addition, the impact of blood pressure and alterations in geometry have not been systematically evaluated.. In 74 FD patients (mean age 36±12 years; 45 females) the extent of myocardial fibrosis and its progression were quantified using cardiac magnetic-resonance-imaging with late enhancement technique (LE). Results were compared to standard echocardiography complemented by 2D-speckle-tracking, 3D-sphericity-index (SI) and standardized blood pressure measurement. At baseline, no patient received enzyme replacement therapy (ERT). After 51±24 months, a follow-up examination was performed.. Systolic blood pressure (SBP) was higher in patients with vs. without LE: 123±17 mmHg vs. 115±13 mmHg; P = 0.04. A positive correlation was found between SI and the amount of LE-positive myocardium (r = 0.51; P<0.001) indicating an association of higher SI in more advanced stages of the cardiomyopathy. SI at baseline was positively associated with the increase of LE-positive myocardium during follow-up. The highest SBP (125±19 mmHg) and also the highest SI (0.32±0.05) was found in the subgroup with a rapidly increasing LE (ie, ≥0.2% per year; n = 16; P = 0.04). Multivariate logistic regression analysis including SI, SBP, EF, left ventricular volumes, wall thickness and NT-proBNP adjusted for age and sex showed SI as the most powerful parameter to detect rapid progression of LE (AUC = 0.785; P<0.05).. LV geometry as assessed by the sphericity index is altered in relation to the stage of the Fabry cardiomyopathy. Although patients with FD are not hypertensive, the SBP has a clear impact on the progression of the cardiomyopathy.

Topics: Adult; Blood Pressure; Cardiomyopathies; Cohort Studies; Disease Progression; Electrocardiography; Fabry Disease; Female; Fibrosis; Follow-Up Studies; Heart Ventricles; Humans; Logistic Models; Magnetic Resonance Imaging; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Ultrasonography

Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.

Topics: Angiotensin II; Animals; Biomarkers; Cardiomyopathies; Cytokines; Denervation; Fibrosis; Heart Atria; Heart Ventricles; Inflammation Mediators; Isoproterenol; Kidney; Kidney Diseases; Male; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Rats, Sprague-Dawley; Renin-Angiotensin System

The aim of the study was to determine the incidence of cirrhotic cardiomyopathy (CCMP), features of its recognition and clinical manifestations.. The study included 102 patients with alcoholic and viral liver cirrhosis (LC) without cardiovascular history, without viremia and signs of acute alcoholic hepatitis. Echocardiography, electrocardiography (ECG) and brain natriuretic hormone (proBNP) level were investigated in all patients.. CCMP signs were detected in 65 (63.7%) of the 102 patients examined. All patients showed signs of electrophysiological myocardial abnormalities in ECG, signs of myocardial injury and the presence of heart failure in echocardiography, increase in proBNP. Interval QT length (0.4689 ± 0.012 s.) was significantly (p = 0.0461) higher than that of the control group. Violation of diastolic relaxation of the left ventricle was detected in 36 (55.6%) patients. The average level of proBNP was 540.85 ± 236.43 pg/ml, significantly different from the level of proBNP in healthy individuals--89.45 ± 26.43 pg/ml. The incidence of CCMP increased progressively with the severity of the Child-Pugh class and was 42.4% in patients of A class, 84.6% (p = 0.0132) in patients of B Class and 100% in patients of C class (p = 0.0219). The length of the QT interval, the proBNP level and frequency of diastolic dysfunction increased with increasing of liver cirrhosis severity.. The frequency of detection of cirrhotic cardiomyopathy was 63.7%. More pronounced CCMP signs were observed in alcoholic liver cirrhosis than in viral. The frequency of detection and severity of cirrhotic cardiomyopathy progres sively increased with the severity of liver cirrhosis. Brain natriuretic peptide was the most sensitive indicator of myocardial damage in liver cirrhosis irrespective of its etiology.

Topics: Adult; Cardiomyopathies; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Natriuretic Peptide, Brain

We aimed to investigate whether nuclear factor kappa-B activation, as evaluated by gene expression of its inhibitor (I-κBα) and cytokine serum levels, was associated with myocardial dysfunction and mortality in children with septic shock. Twenty children with septic shock were prospectively enrolled and grouped according to ejection fraction (EF) <45% (group 1) or EF ≥45% (group 2) on the first day after admission to the pediatric intensive care unit. No interventions were made. In the first day, patients from group 1 (n = 6) exhibited significantly greater tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-10 plasma levels. However, I-κBα gene expression was not different in both groups. Mortality and number of complications were significantly greater in group 1. Patients who died had greater plasma concentrations of TNF-α. In conclusion, TNF-α and IL-10 are involved in myocardial dysfunction accompanying septic shock in children, and TNF-α is associated with mortality.

Topics: Adolescent; Biomarkers; Cardiomyopathies; Child; Child, Preschool; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Hemodynamics; Humans; Infant; Inflammation; Intensive Care Units, Pediatric; Interleukin-10; Longitudinal Studies; Male; Natriuretic Peptide, Brain; NF-kappa B; Prospective Studies; Shock, Septic; Tumor Necrosis Factor-alpha

The cardiac support device supports the heart and mechanically reduces left ventricular (LV) diastolic wall stress. Although it has been shown to halt LV remodeling in dilated cardiomyopathy, its therapeutic efficacy is limited by its lack of biological effects. In contrast, the slow-release synthetic prostacyclin agonist ONO-1301 enhances reversal of LV remodeling through biological mechanisms such as angiogenesis and attenuation of fibrosis. We therefore hypothesized that ONO-1301 plus a cardiac support device might be beneficial for the treatment of ischemic cardiomyopathy.. Twenty-four dogs with induced anterior wall infarction were assigned randomly to 1 of 4 groups at 1 week postinfarction as follows: cardiac support device alone, cardiac support device plus ONO-1301 (hybrid therapy), ONO-1301 alone, or sham control.. At 8 weeks post-infarction, LV wall stress was reduced significantly in the hybrid therapy group compared with the other groups. Myocardial blood flow, measured by positron emission tomography, and vascular density were significantly higher in the hybrid therapy group compared with the cardiac support device alone and sham groups. The hybrid therapy group also showed the least interstitial fibrosis, the greatest recovery of LV systolic and diastolic functions, assessed by multidetector computed tomography and cardiac catheterization, and the lowest plasma N-terminal pro-B-type natriuretic peptide levels (P < .05).. The combination of a cardiac support device and the prostacyclin agonist ONO-1301 elicited a greater reversal of LV remodeling than either treatment alone, suggesting the potential of this hybrid therapy for the clinical treatment of ischemia-induced heart failure.

Topics: Animals; Anterior Wall Myocardial Infarction; Biomarkers; Cardiomyopathies; Cardiovascular Agents; Chemistry, Pharmaceutical; Combined Modality Therapy; Coronary Circulation; Delayed-Action Preparations; Disease Models, Animal; Dogs; Fibrosis; Heart Ventricles; Heart-Assist Devices; Natriuretic Peptide, Brain; Peptide Fragments; Prostaglandins I; Prosthesis Design; Pyridines; Recovery of Function; Time Factors; Ventricular Function, Left; Ventricular Remodeling

Topics: Cardiomyopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sleep Apnea, Obstructive; Troponin T

Topics: Cardiomyopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sleep Apnea, Obstructive; Troponin T

Topics: Cardiomyopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sleep Apnea, Obstructive; Troponin T

Mitoxantrone (MTX) has been shown to reduce progression of disability and number of clinical exacerbations in patients with progressive multiple sclerosis (MS). Prolonged administration of MTX, however, is limited by the risk of cardiotoxicity. Cardiac monitoring in MTX-treated patients includes usually measurement of left ventricular ejection fraction (LVEF) by means of echocardiography. The N-terminal pro-brain natriuretic peptide (NT-proBNP) represents a novel diagnostic tool in the assessment of heart failure. This study was aimed to evaluate the usefulness of NT-proBNP for early detection of MTX-induced cardiotoxicity in MS patients.. We measured the NT-proBNP plasma levels in 45 MS patients who completed 24-month MTX therapy and in 37 MS patients of control group.. The median NT-proBNP plasma value was 15.12pg/mL. In 12 MTX-treated patients (27%), NT-proBNP plasma values were elevated, though this subgroup of patients neither clinical showed evidence of myocardial damage nor had the LVEF value <50%. In five patients with normal NT-proBNP, we observed LVEF decline >10%. We did not observe correlations between the NT-proBNP levels and patient age, MS duration, relapses index, Extended Disability Status Scale (EDSS), MTX single dose and the total cumulative dose of MTX. In 8 patients (22%) from control group, NT-proBNP plasma levels were also elevated.. The results of our study confirm that MTX therapy is safe for carefully selected and closely monitored MS patients. We believe that serial evaluation of NT-proBNP levels (before, during and after MTX therapy) can identify MS patients at high risk for MTX-induced cardiotoxicity.

Topics: Adult; Antineoplastic Agents; Biomarkers; Cardiomyopathies; Female; Heart Diseases; Heart Failure; Humans; Male; Middle Aged; Mitoxantrone; Multiple Sclerosis; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

Elevated plasma B-type natriuretic peptide (BNP) levels in patients with critical sepsis (severe sepsis and septic shock) may indicate septic cardiomyopathy. However, multiple heterogeneous conditions may also be involved in increased BNP level. In addition, the prognostic value of BNP in sepsis remains debatable. In this study, we sought to discover potential independent determinants of BNP elevation in critical sepsis. The prognostic value of BNP was also evaluated.. In this observational study, we enrolled mechanically ventilated, critically septic patients requiring hemodynamic monitoring through a pulmonary artery catheter. All clinical, laboratory and survival data were prospectively collected. Plasma BNP concentrations were measured daily for five consecutive days. Septic cardiomyopathy was assessed on day 1 on the basis of left and right ventricular ejection fractions (EF) derived from echocardiography and thermodilution, respectively. Mortality was recorded at day 28.. A total of 42 patients with severe sepsis (N = 12) and septic shock (N = 30) were ultimately enrolled. Daily BNP levels were significantly elevated in septic shock patients compared with those with severe sepsis (P ≤0.002). Critical illness severity (assessed by Acute Physiology and Chronic Health Evaluation II and maximum Sequential Organ Failure Assessment scores), and peak noradrenaline dose on day 1 were independent determinants of BNP elevation (P <0.05). Biventricular EFs were inversely correlated with longitudinal BNP measurements (P <0.05), but not independently. Pulmonary capillary wedge pressures (PCWP) and volume expansion showed no correlation with BNP. In septic shock, increased central venous pressure (CVP) and CVP/PCWP ratio were independently associated with early BNP values (P <0.05).. The severity of critical illness, rather than septic cardiomyopathy, is probably the major determinant of BNP elevation in patients with critical sepsis. Daily BNP values are of limited prognostic value in predicting 28-day mortality; however, fast BNP decline over time and a decrease in BNP <500 pg/ml may imply a favorable outcome.

Topics: Adult; Biomarkers; Cardiomyopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Sepsis; Survival Analysis

BNP is increasingly utilized in the management of pediatric HT recipients. Performing a retrospective single-center chart review, we sought to describe BNP changes during the first year after HT and identify factors that affect its trend. After exclusion for rejection, 316 BNP levels from 50 patients were evaluated. BNP underwent an exponential decline 120 days after HT followed by a plateau. Log10 BNP decline strongly correlated with time (r = -0.70, p < 0.0001). Initial BNP was less in pretransplant VAD (p = 0.0016) and lower post-HT inotrope use (p = 0.0043). Infant recipients, IT >4 h, and those bridged medically were associated with higher plateau BNP. Multivariable logistic regression demonstrated IT >4 h independently predicted plateau BNP in the upper quartile (OR 7.1, p = 0.02). No significant change in BNP coincided with rejection (N = 6 patients) without severe hemodynamic compromise. BNP correlated modestly with right atrial pressure (r = 0.4652, p < 0.0001) and pulmonary capillary wedge pressure (r = 0.2660, p < 0.001), but poorly with echocardiogram (r = -0.18, p = 0.003). Trending BNP could help provide insight into how the graft recovers after HT and IT >4 h independently predicted higher plateau BNP and may reflect subtle changes in graft performance.

Topics: Adolescent; Biomarkers; Cardiomyopathies; Child; Child, Preschool; Female; Graft Rejection; Heart Defects, Congenital; Heart Transplantation; Hemodynamics; Humans; Infant; Male; Myocardium; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Retrospective Studies; Treatment Outcome

Troponin-T (cTnT) and NT-proBNP provide prognostic information in light-chain amyloidosis (AL). Thus, these biomarkers are widely used in clinical routine for risk stratification. Recently, plasma level of osteopontin (OPN), a secreted phosphoglycoprotein expressed by a variety of cell types, has been reported as a risk predictor in various cardiovascular diseases.. OPN was determined retrospectively in 150 consecutive patients newly diagnosed with AL amyloidosis. All patients were evaluated according to a routine protocol including electrocardiography, echocardiography and laboratory testing.. Mean OPN was 591 ± 37 ng/mL. Cardiac involvement was established in 83 (55.3%). Median OPN plasma level were associated with number of organs involved, renal function, eligibility for high-dose melphalan chemotherapy and autologous stem cell transplantation, and severity of cardiac amyloidosis. Median follow-up was 19.2 months. 1-year all-cause-survival was 83.4%. The cut-offs discriminating 1-year all-cause-mortality for NT-proBNP, troponin T, and OPN were 2544 ng/L, 0.035 µg/L, and 426.8 ng/mL, respectively. Outcome was worse in patients with biomarkers above the individual ROC derived cut-off. A significant improvement of survival was observed in patients with cTNT >0.035 µg/L or NT-proBNP >2544 ng/L and OPN below ROC-derived cut-off of 426.8 ng/mL as compared to patients with OPN above 426.8 ng/L. No further discrimination was achieved by OPN in the cohorts of low troponin T or low NT-proBNP, respectively. Separate multivariate models identified OPN (cut-off 426.8 ng/mL) and troponin T (cut-off 0.035 µg/L) as independent predictors of all-cause-mortality.. These data demonstrated that OPN appears to be a valuable marker in the clinical routine for evaluation of patients with AL amyloidosis, especially if it is used in combination with cTNT and/or NT-proBNP.

Topics: Aged; Amyloidosis; Antineoplastic Agents, Alkylating; Biomarkers; Cardiomyopathies; Female; Gene Expression; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Male; Melphalan; Middle Aged; Natriuretic Peptide, Brain; Osteopontin; Peptide Fragments; Prognosis; Retrospective Studies; ROC Curve; Stem Cell Transplantation; Survival Analysis; Transplantation, Autologous; Troponin T

Increased myocardial trabeculations define noncompaction cardiomyopathy (NCC). Imaging advancements have led to increasingly common identification of prominent trabeculations with unknown implications. We quantified and determined the impact of trabeculations' burden on cardiac function and stretch in a population of healthy young adults. One hundred adults aged 18 to 35 years (28±4 years, 55% women) without known cardiovascular disease were prospectively studied by cardiovascular magnetic resonance. Left ventricular (LV) volumes, segmental function, and ejection fraction (EF) and left atrial volumes were determined. Thickness and area of trabeculated (T) and dense (D) myocardium were measured for each standardized LV segment. N-terminal pro-brain natriuretic peptide (Nt-pro-BNP) was measured. Eighteen percent of the subjects had ≥1 positive traditional criteria for NCC, and 11% meet new proposed NCC cardiovascular magnetic resonance criteria. Trabeculated over dense myocardium ratio (T/D) ratios were uniformly greater at end-diastole versus end-systole (0.90±0.25 vs 0.42±0.13, p<0.0001), in women versus men (0.85±0.24 vs 0.72±0.19, p=0.006), at anterior versus nonanterior segments (1.41±0.59 vs 0.88±0.35, p<0.0001), and at apical versus nonapical segments (1.31±0.56 vs 0.87±0.38, p<0.0001). The largest T/D ratios were associated with lower LVEF (57.0±5.3 vs 62±5.5, p=0.0001) and greater Nt-pro-BNP (203±98 vs 155±103, p=0.04). Multivariable regression identified greater end-systolic T/D ratios as the strongest independent predictor of lower LVEF, beyond age and gender, left atrial or LV volumes, and Nt-pro-BNP (β=-9.9, 95% CI -15 to 4.9, p<0.001). In conclusion, healthy adults possess variable amounts of trabeculations that regularly meet criteria for NCC. Greater trabeculations are associated with decreased LV function. Apparently healthy young adults with increased trabecular burden possess evidence of mildly impaired cardiac function.

Topics: Adolescent; Adult; Cardiomyopathies; Diastole; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Heart Atria; Heart Ventricles; Humans; Magnetic Resonance Imaging, Cine; Male; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Protein Precursors; Reference Values; Risk Factors; Surveys and Questionnaires; Young Adult

Topics: Atrial Fibrillation; Biomarkers; Cardiomyopathies; Collagen Type III; Disease Progression; Fibrosis; Humans; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Transforming Growth Factor beta1

Twenty to thirty percent of persons with Trypanosoma cruzi infection eventually develop cardiomyopathy. If an early indicator were to be identified and validated in longitudinal studies, this could enable treatment to be prioritized for those at highest risk. We evaluated cardiac and extracellular matrix remodeling markers across cardiac stages in T. cruzi infected (Tc+) and uninfected (Tc-) individuals.. Participants were recruited in a public hospital in Santa Cruz, Bolivia and assigned cardiac severity stages by electrocardiogram and echocardiogram. BNP, NTproBNP, CKMB, troponin I, MMP-2, MMP-9, TIMP-1, TIMP-2, TGFb1, and TGFb2 were measured in specimens from 265 individuals using multiplex bead systems. Biomarker levels were compared between Tc+ and Tc- groups, and across cardiac stages. Receivers operating characteristic (ROC) curves were created; for markers with area under curve>0.60, logistic regression was performed.. Analyses stratified by cardiac stage showed no significant differences in biomarker levels by Tc infection status. Among Tc+ individuals, those with cardiac insufficiency had higher levels of BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 than those with normal ejection fraction and left ventricular diameter. No individual marker distinguished between the two earliest Tc+ stages, but in ROC-based analyses, MMP-2/MMP-9 ratio was significantly higher in those with than those without ECG abnormalities.. BNP, NTproBNP, troponin I, MMP-2, TIMP-1, and TIMP-2 levels rose with increasing severity stage but did not distinguish between Chagas cardiomyopathy and other cardiomyopathies. Among Tc+ individuals without cardiac insufficiency, only the MMP-2/MMP-9 ratio differed between those with and without ECG changes.

Topics: Adult; Aged; Biomarkers; Bolivia; Cardiomyopathies; Chagas Cardiomyopathy; Electrocardiography; Female; Humans; Male; Matrix Metalloproteinase 9; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

The occurrence of cardiac dysfunction is common after subarachnoid hemorrhage (SAH) and was hypothesized to be related to the release of endogenous catecholamines. The aim of this prospective study was to evaluate the relationship between endogenous catecholamine and cardiac dysfunction at the onset and during the first week after SAH.. Forty consecutive patients admitted for acute SAH without known heart disease were included. Catecholamine plasma concentrations and transthoracic echocardiography (TTE) were documented on admission, on day 1 (D1), and day 7 (D7).. At baseline, 24 patients had a World Federation of Neurosurgical Societies score (WFNS) of one or two; the remaining 16 had a WFNS between three and five. Twenty patients showed signs of cardiac dysfunction on admission, including six with left ventricle (LV) systolodiastolic dysfunction and 14 with pure LV diastolic dysfunction. On admission, norepinephrine, epinephrine, dopamine, B-type Natriuretic Peptide (BNP) and Troponin Ic (cTnI) plasmatic levels were higher in patients with the higher WFNS score and in patients with altered cardiac function (all P <0.05). Among patients with cardiac injury, heart function was restored within one week in 13 patients, while seven showed persistent LV diastolic dysfunction (P = 0.002). Plasma BNP, cTnI, and catecholamine levels exerted a decrease towards normal values between D1 and D7.. Our findings show that cardiac dysfunction seen early after SAH was associated with both a rapid and sustained endogenous catecholamine release and WFNS score. SAH-induced cardiac dysfunction was regressive over the first week and paralleled the normalization of catecholamine concentration.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Catecholamines; Echocardiography; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Subarachnoid Hemorrhage; Time Factors; Troponin I; Ventricular Dysfunction, Left

Cardiac amyloidosis due to amyloid fibril deposition in the heart results in cardiomyopathy (CMP) with heart failure (HF) and/or conduction disturbances. Immunoglobulin light chain-related CMP (AL-CMP) features rapidly progressive HF with an extremely poor prognosis compared with a CMP due to the deposition of mutant (ATTR) amyloidosis or wild-type (senile systemic amyloidosis, SSA) transthyretin (TTR) proteins. Amyloid fibril deposition disrupts the myocardial extracellular matrix (ECM) homeostasis, which is partly regulated by matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). We therefore tested the hypothesis that circulating levels of MMPs and TIMPs in patients with AL-CMP and TTR-related CMP (TTR-CMP) are dissimilar and indicative of cardiac amyloid disease type.. Fifty AL-CMP patients were compared with 50 TTR-CMP patients (composed of 38 SSA and 12 ATTR patients). Clinical and laboratory evaluations including echocardiography were performed at the initial visit to our center and analyzed. Serum MMP-2, MMP-9, TIMP-1, and TIMP-2 levels were determined by ELISA. Compared with TTR-CMP patients, AL-CMP patients had higher levels of brain natriuretic peptide (BNP), troponin I (TnI), MMP-2, TIMP-1, and MMP-2/TIMP-2 ratio, despite less left ventricular (LV) hypertrophy and better preserved LV ejection fraction. Mortality was worse in AL-CMP patients than in TTR-CMP patients (log-rank P<0.01). MMP-2/TIMP-2 plus BNP and TnI showed the highest discriminative ability for distinguishing AL-CMP from TTR-CMP. Female sex (HR, 2.343; P=0.049) and BNP (HR, 1.041; P<0.01) were predictors for mortality for all patients with cardiac amyloidoses. Only BNP was a predictor of death in AL-CMP patients (HR, 1.090; P<0.01). There were no prognostic factors for all-cause death in TTR-CMP patients.. Circulating concentrations of MMPs and TIMPs may be useful in differentiating patients with AL-CMP from those with TTR-CMP, resulting in earlier diagnostic vigilance, and may add prognostic information. In addition to an elevated BNP level, female sex increased the risk of death in patients with cardiac amyloidoses.

Topics: Aged; Amyloid Neuropathies, Familial; Amyloidosis; Cardiomyopathies; Extracellular Matrix; Female; Humans; Hypertrophy, Left Ventricular; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Myocardium; Natriuretic Peptide, Brain; Stroke Volume; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinases; Troponin I; Ultrasonography

Cardiac amyloidosis is a fatal disease whose prognosis and treatment rely on identification of the amyloid type. In our aging population transthyretin amyloidosis (ATTRwt) is common and must be differentiated from other amyloid types. We report the clinical presentation, natural history, and prognostic features of ATTRwt compared with cardiac-isolated AL amyloidosis and calculate the probability of disease diagnosis of ATTRwt from baseline factors.. All patients with biopsy-proven ATTRwt (102 cases) and isolated cardiac AL (36 cases) seen from 2002 to 2011 at the UK National Amyloidosis Center were included. Median survival from the onset of symptoms was 6.07 years in the ATTRwt group and 1.7 years in the AL group. Positive troponin, a pacemaker, and increasing New York Heart Association (NYHA) class were associated with worse survival in ATTRwt patients on univariate analysis. All patients with isolated cardiac AL and 24.1% of patients with ATTRwt had evidence of a plasma cell dyscrasia. Older age and lower N-terminal pro-B-type natriuretic peptide (NT pro-BNP) were factors significantly associated with ATTRwt. Patients aged 70 years and younger with an NT pro-BNP <183 pmol/L were more likely to have ATTRwt, as were patients older than 70 years with an NT pro-BNP <1420 pmol/L.. Factors at baseline associated with a worse outcome in ATTRwt are positive troponin T, a pacemaker, and NYHA class IV symptoms. The age of the patient at diagnosis and NT pro-BNP level can aid in distinguishing ATTRwt from AL amyloidosis.

Topics: Aged; Amyloid; Amyloidosis; Biopsy; Cardiomyopathies; Disease Progression; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prealbumin; Prognosis; Referral and Consultation

There is no reliable method of screening for pregnant women at high risk of developing severe myocardial disorders. In this study, we used vector-projected 187 channel electrocardiography (DREAM-ECG) and serum biochemical markers to evaluate peripartum myocardial burden in pregnant women. Forty-one pregnant women were examined at 36-37 weeks gestation (GW36), 7 days postpartum (PPD7), and 1 month postpartum (PPM1). Ten non-pregnant control women were assessed at a single time point. Heart rate, sympathetic index, and repolarization index (RTc dispersion) were quantified using the DREAM-ECG system, and serum levels of NT-proBNP, cardiac troponin T, estrogen, and progesterone were determined. Heart rate and the sympathetic index decreased from GW36 to PPM1 (P = 0.0031). The repolarization index decreased over time and was greater than in non-pregnant controls (31 ± 13 ms). Estrogen and progesterone at PPD7 and PPM1 were significantly lower than those at GW36 (P < 0.0001, P < 0.001). NT-proBNP at PPD7 was greater than at GW36 (median 29 pg/mL at GW36, 86 pg/mL at PPD7), and decreased at PPM1 in comparison to PPD7 (median 18.5 pg/mL). Troponin T was in the normal range during the whole period (< 0.003 ng/mL). In conclusion, these results indicate that the peripartum myocardial burden in pregnant women does not return to normal nonpregnant levels by PPM1. We propose that both repolarization indexes such as RTc dispersion by DREAM-ECG and serum biochemical markers may identify pregnant women at high risk of developing severe myocardial damage in the peripartum period.

Topics: Adult; Biomarkers; Cardiomyopathies; Electrocardiography; Female; Humans; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Troponin T; Young Adult

This study aimed to investigate the effects of rosuvastatin on TGF-beta1 expression, cardiac fibrosis, ventricular remodeling and cardiac function in diabetic cardiomyopathy rats. Twenty-seven diabetic rats induced by streptozotocin intraperitoneal injection were randomly divided into three groups, viz. diabetic, rosuvastatin low-dose (Ros-L) and high dose group (Ros-H). Intervention group were given rosuvastatin 2 mg/kg/d and 5 mg/kg/d orally, respectively. After 10 weeks, the levels of glycosylated hemoglobin (HbA1c), creatine phosphokinase isoenzyme (CK-MB), plasma brain natriuretic peptide (BNP), myocardial collagen volume fraction (CVF) and left ventricular mass index (LVWI) were measured. CK-MB levels in Ros-H and Ros-L rats were lower than in the diabetic group. Rosuvastatin alleviated myofibrosis cordis and fibroplastic proliferation. LVWI, BNP, CVF and TGF-beta1 mRNA and protein levels in the diabetic group were higher than in the control, but were reduced after rosuvastatin treatment. These results demonstrate that rosuvastatin dose-dependently reduces TGF-beta1 expression and inhibits the development of myocardial fibrosis in diabetic cardiomyopathy.

Topics: Animals; Body Weight; Cardiomyopathies; Collagen; Creatine Kinase; Diabetes Mellitus, Experimental; Diabetic Cardiomyopathies; Fibrosis; Fluorobenzenes; Glycated Hemoglobin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Pyrimidines; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Rosuvastatin Calcium; Sulfonamides; Transforming Growth Factor beta1

To investigate the association of serum sTREM-1 with myocardial dysfunction in patients with severe sepsis.. A total of 85 patients with severe sepsis were divided into severe sepsis group (n = 40) and septic shock group (n = 45). Serum levels of sTREM-1, NT-proBNP, APACHE II score, SOFA score, cardiac index, cardiac function index, global ejection fraction, and left ventricular contractility index were measured on days 1, 3, and 7 after admission to ICU.. Serum sTREM-1 levels of patients with septic shock were significantly higher than those with severe sepsis on days 1, 3, and 7. Serum sTREM-1 was positively correlated with APACHE II scores, SOFA scores, and NT-proBNP. However, The sTREM-1 level was markedly negatively correlated with CI, CFI, GEF, and dP/dt max, respectively. Multiple logistic regression analysis showed that sTREM-1 was independent risk factor to NT-proBNP increasing. The optimal cut-off point of sTREM-1 for detecting patients with myocardial dysfunction was 468.05 ng/mL with sensitivity (80.6%) and specificity (75.7%). There is no difference in TREM-1-mRNA expression between the two groups.. Serum sTREM-1 is significantly associated with myocardial dysfunction and may be a valuable tool for determining the presence of myocardial dysfunction in patients with severe sepsis.

Topics: Aged; Cardiomyopathies; Female; Heart Ventricles; Humans; Male; Membrane Glycoproteins; Middle Aged; Myeloid Cells; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Immunologic; Regression Analysis; RNA, Messenger; Sensitivity and Specificity; Sepsis; Severity of Illness Index; Shock, Septic; Triggering Receptor Expressed on Myeloid Cells-1

To evaluate the prevalence and the prognostic implications of conduction delays in a large cohort of cardiac AL patients.. Echo Doppler and 12-lead ECG were collected in 344 consecutive patients in whom diagnosis of AL amyloidosis was concluded between 2008 and 2010. Patients were subdivided according to the presence (n = 240) or absence (n = 104) of cardiac involvement.. When compared with patients without myocardial involvement, cardiac AL was associated with prolonged PQ, QRS, QT and QTc intervals (P < 0.05), and with higher prevalence of intraventricular blocks (27.5% vs. 16.5%, P < 0.05), that was associated with higher wall thickness, worse diastolic and regional systolic function, higher NT-proBNP values (all P < 0.05), and higher mortality (P = 0.0001; median follow-up: 402 days).. Intraventricular conduction delays have a negative prognostic impact in patients with cardiac AL amyloidosis. Their presence should not be overlooked in the diagnostic workup, prompting a more accurate cardiological support.

Topics: Age Distribution; Aged; Amyloidosis; Analysis of Variance; Arrhythmias, Cardiac; Biomarkers; Brugada Syndrome; Cardiac Conduction System Disease; Cardiomyopathies; Cohort Studies; Echocardiography, Doppler; Electrocardiography; Female; Heart Conduction System; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; Proportional Hazards Models; Reference Values; Retrospective Studies; Risk Assessment; Severity of Illness Index; Sex Distribution; Statistics, Nonparametric; Survival Rate

Familial amyloid polyneuropathy (FAP) mainly targets the peripheral nervous system and heart. Early noninvasive detection of cardiac impairment is critical for therapeutic management.. To assess if amino-terminal pro-brain natriuretic peptide (NT-proBNP) or troponin T (cTnT) can predict echocardiographic left-ventricle (LV) impairment in FAP.. Thirty-six asymptomatic carriers and patients with FAP had echocardiographic measurement of left-ventricular (LV) systolic function, hypertrophy (LVH) and estimation of filling pressure (FP).. Overall, median age, NT-proBNP, and LV ejection fraction were, respectively, 59 years (41-74), 323 pg/ml (58-1960), and 60% (51-66). Twelve patients had increased cTnT. Prevalence of ATTR gene mutations was 53% for Val30Met. Four individuals were asymptomatic, 6 patients had isolated neurological clinical signs, and 26 had echo-LV abnormalities. The ROC curve identified NT-proBNP patients with echo-LV abnormalities (area: 0.92; (0.83-0.99), p = 0.001) at a threshold >82 pg/ml with a sensitivity of 92%, and a specificity of 90%. Increased in NT-proBNP occurred in patients with SD and/or LVH with or without increase in FP. Elevated cTnT (>0.01 ng/ml) was only observed in patients with LVH and systolic dysfunction, with or without FP.. In FAP, NT-proBNP was associated with cardiac impairment suggesting that NT-proBNP could be used in carriers or in FAP patients with only neurologic symptoms for identifying the appropriate time to start cardiac echocardiographic assessment and follow-up. cTnT identified patients with severe cardiac disease.

Topics: Adult; Aged; Amyloid Neuropathies, Familial; Cardiomyopathies; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Left ventricular hypertrophy (LVH), a common complication in chronic kidney disease (CKD), is associated with high cardiovascular mortality. The aim of this experimental study was to analyze the effect of different vitamin D receptor activators (VDRAs) on both LVH and myocardial fibrosis in chronic renal failure (CRF).. Male Wistar rats with CRF, carried out by 7/8 nephrectomy, were treated intraperitoneally with equivalent doses of VDRAs (calcitriol, paricalcitol and alfacalcidol, 5 days per week) during 4 weeks. A placebo group (CRF + vehicle) and a Sham group with normal renal function served as controls. Biochemical, morphological, functional and molecular parameters associated with LVH were evaluated, as well as cardiac fibrosis, collagen I, transforming growth factor β1 (TGFβ1) and matrix metalloproteinase-1 (MMP1) expression.. All VDRAs treatment prevented LVH, with values of cardiomyocyte size, LV wall and septum thickness and heart-body weight ratio similar to those observed in the Sham group. At molecular levels, all VDRAs attenuated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) expression compared with CRF + vehicle. The phosphorylation of ERK1/2, a signal for activating growth, was stimulated in the CRF + vehicle group; VDRAs use prevented this activation. Paricalcitol was the only VDRA used that maintained in the normal range all parameters associated with myocardial fibrosis (total collagen, collagen I, TGFβ1 and MMP1).. Our findings demonstrated that the three VDRAs used induced similar changes in bone metabolic parameters and LVH. In addition, paricalcitol was the only VDRA which showed a relevant beneficial effect in the reduction of myocardial fibrosis, a key factor in the myocardial dysfunction in CKD patients.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Bone Density Conservation Agents; Calcitriol; Cardiomyopathies; Ergocalciferols; Fibrosis; Humans; Hydroxycholecalciferols; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; MAP Kinase Signaling System; Natriuretic Peptide, Brain; Phosphorylation; Rats; Rats, Wistar; Receptors, Calcitriol

Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations.. To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation.. We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction.. COPD exacerbation frequency was related to stable-state arterial stiffness (rho = 0.209; P = 0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean ± SD aPWV, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms(-1); P = 0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n = 55) and fell slowly during recovery. In those with airway infection at exacerbation (n = 24) this rise was greater (1.4 ± 1.6 vs. 0.7 ± 1.3 ms(-1); P = 0.048); prolonged; and related to sputum IL-6 (rho = 0.753; P < 0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n = 12) than those without (n = 43) (mean ± SD increase in troponin T, 0.011 ± 0.009 vs. 0.003 ± 0.006 μg/L, P = 0.003; N-terminal pro-brain natriuretic peptide, 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml, P < 0.001).. Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.

Topics: Aged; Aged, 80 and over; Aorta; Blood Pressure; C-Reactive Protein; Cardiomyopathies; Cardiovascular Diseases; Cohort Studies; Disease Progression; Female; Fibrinogen; Heart Rate; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Pulmonary Disease, Chronic Obstructive; Pulse Wave Analysis; Risk Factors; Spirometry; Sputum; Troponin T; Vascular Stiffness

Cardiac involvement is a dominant prognostic factor in AL amyloidosis patients. A detailed assessment of the presence and degree of cardiac involvement utilizes an array of noninvasive investigation methods, particularly echocardiography and MRI; laboratory parameters include troponins and natriuretic peptides. Cardiac involvement detection aside, cardiac bio-markers are used as a relatively strong stratification and prognostic factor.. The presentation of cardiac bio-markers assay applications in AL amyloidosis patients at an individual treatment center.. The monitored patient set consisted of 22 patients with histologically confirmed AL amyloidosis, of whom 18 met the criteria for cardiac involvement. Levels of cardiac bio-markers troponin T (TnT) and Nterminal probrain natriuretic peptide (NT ProBNP) were determined in all patients. Risk stratification of the patients utilized the Mayo staging system which is based on both bio-markers assays; Log Rank Test was applied to survival evaluation.. Median survival of patients with cardiac involvement stigmata was 10 months vs 60 months survival of patients without signs of cardiac involvement (p = 0.133). Of the 4 patients without cardiac involvement, 1 has shown positive levels of TnT and 2 positive levels of NT ProBNP. All cardiac involvement patients exhibited abnormal levels of NT ProBNP (median 4,752 ng/ l; 415.7- 35,000) as well as positive levels of TnT (median 0.0815 μg/ l; 0.02- 0.986). The application of the Mayo stratification system to the set had determined 2 patients at stage I, 5 patients at stage II and 15 patients at stage III. The median survival of the Mayo I + II group vs the Mayo III group was 60 vs 6 months (p = 0.015), revealing extremely limited survival of stage III patients. Assessment of TnT and NT ProBNP levels relative to treatment response shows that the degree of decrease in both markers depends on maximum treatment response -  respectively the attainment of a complete hematological remission.. The results, although obtained from a limited set of patients, confirm a definitive benefit of the application of cardiac bio-markers assay in the diagnostic and therapeutic algorithm of AL amyloidosis patients. The Mayo stratification system utilizing the cardiac indicator values represents a robust tool for risk stratification of AL amyloidosis patients.

Topics: Adult; Aged; Amyloid; Amyloidosis; Biomarkers; Cardiomyopathies; Echocardiography; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Troponin T

Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality, although the underlying mechanisms are not well understood.. We aimed to determine whether more severe OSA, measured by the Respiratory Disturbance Index (RDI), is associated with subclinical myocardial injury and increased myocardial wall stress.. A total of 1,645 participants (62.5 ± 5.5 yr and 54% women) free of coronary heart disease and heart failure and participating in both the Atherosclerosis Risk in the Communities and the Sleep Heart Health Studies underwent overnight polysomnography and measurement of high-sensitivity troponin T (hs-TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP).. OSA severity was defined using conventional clinical categories: none (RDI ≤ 5), mild (RDI 5-15), moderate (RDI 15-30), and severe (RDI > 30). Hs-TnT, but not NT-proBNP, was associated with OSA after adjusting for 17 potential confounders (P = 0.02). Over a median of 12.4 (interquartile range, 11.6-13.1) years follow-up, hs-TnT was related to risk of death or incident heart failure in all OSA categories (P ≤ 0.05 in each category).. In middle-aged to older individuals, OSA severity is independently associated with higher levels of hs-TnT, suggesting that subclinical myocardial injury may play a role in the association between OSA and risk of heart failure. OSA was not associated with NT-proBNP levels after adjusting for multiple possible confounders.

Topics: Aged; Asymptomatic Diseases; Biomarkers; Cardiomyopathies; Cross-Sectional Studies; Female; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Polysomnography; Proportional Hazards Models; Risk Factors; Severity of Illness Index; Sleep Apnea, Obstructive; Troponin T

Topics: Cardiomyopathies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sleep Apnea, Obstructive; Troponin T

Tachycardia-induced cardiomyopathy (TCM) is a reversible cause of heart failure. Little is known of the characteristics of tachycardia associated with the development of left ventricular (LV) dysfunction and the reversal of cardiomyopathy after cure of tachycardia. This study aimed to examine the reversal of cardiomyopathy in patients undergoing ablation with congestive heart failure secondary to tachycardia.. A total of 625 patients underwent radiofrequency ablation for tachycardiarrhymias between January 2009 and July 2011. Echocardiography analysis was performed to identify patients with depressed LV function, defined as a left ventricular ejection fraction <50 %. Patients with preexisting structural heart disease (n = 10) were excluded. NT-pro-B-type natriuretic peptide (NT-proBNP) assessment was performed before ablation in patients considered to have TCM (n = 17). Repeated echocardiography study and NT-proBNP assessment were measured after a mean follow-up of 3 months. Levels of NT-proBNP before and after ablation were compared. Reversal of cardiomyopathy was also assessed.. The incidence of TCM was 2.7 % (12 males; age, 35.8 ± 17.1 years). Successful ablation was performed in 16 of 17 patients (94.1 %). There was a significant improvement in left ventricular ejection fraction (36.7 ± 7.5 vs. 59.4 ± 9.7 %; P < 0.001). The mean left ventricular end-diastolic diameter before treatment was 59.5 ± 8.3 mm (range, 43 to 70), compared with 51.9 ± 7.4 mm (range, 40 to 67) (P = 0.009) after 3 months follow-up. The levels of NT-proBNP decreased after ablation procedure, from 4,092.6 ± 3,916.6 to 478.9 ± 881.9 pg/ml (P < 0.001). After successful ablation, ventricular function normalized in 15 of 17 (88.2 %) patients at a mean of 3 months.. Restoration of LV function and reversal of LV remodeling can be achieved with successful elimination of tachycardia in the majority of patients. NT-proBNP level elevates in subjects with TCM and decreases sharply after ablation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiomyopathies; Catheter Ablation; Chi-Square Distribution; Child; Echocardiography; Electrocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Statistics, Nonparametric; Tachycardia; Treatment Outcome; Ventricular Dysfunction, Left

After atrial redirection surgery (Mustard-Senning operations) for transposition of the great arteries (TGA), the systemic right ventricle (RV) suffers from late systolic failure with high morbidity and mortality. Mechanisms of late RV failure are poorly characterized. We hypothesized that diffuse interstitial expansion representing diffuse fibrosis is greater in systemic RVs of patients following Mustard-Senning surgery and that it would be associated with other markers of heart failure and disease severity.. We used equilibrium contrast cardiovascular magnetic resonance (CMR) imaging to quantify extracellular volume (ECV) in the septum and RV free wall of 14 adults presenting to a specialist clinic late after surgery for TGA (8 Mustard, 6 female, median age 33). These were compared with 14 age-and sex-matched healthy volunteers. Patients were assessed with a standardized CMR protocol, NT-brain natriuretic peptide (NT-proBNP), and cardiopulmonary exercise (CPEX) testing. The mean septal ECV was significantly higher in patients than controls (0.254 ± 0.036 vs. 0.230 ± 0.032; P = 0.03). NT-proBNP positively related to septal ECV (P = 0.04; r = 0.55). The chronotropic index (CI) during CPEX testing negatively related to the ECV (P = 0.04; r = -0.58). No relationship was seen with other CMR or CPEX parameters. R.V free wall ECV was difficult to measure (heavy trabeculation, sternal wires, blood pool in regions of interest) with high and poor inter-observer reproducibility: this analysis was abandoned.. Septal interstitial expansion is seen in adults late after atrial redirection surgery for TGA. It correlates well with NT-proBNP and CI and may have a role in the development of RV systolic impairment. Measuring interstitial expansion in the RV free wall is difficult using this methodology.

Topics: Adult; Analysis of Variance; Cardiac Surgical Procedures; Cardiomyopathies; Case-Control Studies; Cohort Studies; Contrast Media; Exercise Test; Female; Fibrosis; Follow-Up Studies; Gadolinium; Heart Ventricles; Humans; Image Enhancement; Magnetic Resonance Imaging, Cine; Male; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values; Severity of Illness Index; Statistics, Nonparametric; Transposition of Great Vessels; Ultrasonography; Ventricular Dysfunction, Right

To evaluate the relationship between pulmonary and myocardial fibrosis in patients with systemic sclerosis (SS).. Eighteen patients with SS prospectively underwent cardiac magnetic resonance imaging (CMR) and high-resolution computed tomography (HRCT) of the chest. Cardiac biomarkers (N-terminal pro B-type natriuretic peptide) and quality-of-life measures (SF-36 and SS health assessment questionnaires) were assessed. Two readers blinded to other test results evaluated the CMRs in consensus for functional left and right ventricular parameters and for myocardial late enhancement. HRCT images were reviewed at 5 levels and scored for total disease extent, extent of reticulation, proportion of ground-glass opacities (GGO), and coarseness of reticulation.. Right ventricular ejection fraction correlated significantly with the percentage of late enhancement of the myocardium (R=0.63, P<0.01), extent of pulmonary fibrosis (R=0.57, P<0.01), and extent of GGO (R=0.53, P<0.05). Significant correlations were also found between the percentage of late enhancement of the myocardium and the extent of overall pulmonary fibrosis (R=0.59, P<0.05) and the extent of the ground-glass subcomponent (R=0.58, P<0.05). N-terminal pro B-type natriuretic peptide correlated significantly with the number of myocardial segments with late enhancement (R=0.64, P<0.05). Stepwise multiple linear regression revealed the extent of pulmonary GGO to be the only independent predictor of the percentage of myocardial enhancement (R2=0.61, P<0.0001).. In patients with SS with pulmonary fibrosis on HRCT images, CMR may be a useful test to detect early-stage myocardial fibrosis.

Topics: Adult; Aged; Analysis of Variance; Biomarkers; Cardiomyopathies; Case-Control Studies; Contrast Media; Endomyocardial Fibrosis; Female; Gadolinium DTPA; Humans; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pulmonary Fibrosis; Quality of Life; Regression Analysis; Scleroderma, Systemic; Surveys and Questionnaires; Tomography, X-Ray Computed

Familial amyloid polyneuropathy (FAP) is a dominantly inherited multi-system disease associated with transthyretin (TTR) mutations. Previous series have predominantly described patients with the TTR variant Val30Met (V30M), which is the most prevalent cause of FAP worldwide. Here, we report the dominant cardiac phenotype and outcome of FAP associated with TTR Thr60Ala (T60A), the most common UK variant.. Sixty consecutive patients with FAP associated with TTR T60A (FAP T60A) were prospectively evaluated in two centres between 1992 and 2009. Median (range) age of symptom development was 63 (45-78) years. A family history of amyloidosis was present in only 37%. Autonomic and peripheral neuropathy were present in 44 and 32 patients, respectively, at diagnosis. Cardiac involvement was evident on echocardiography at diagnosis in 56 patients, but was associated with reduced QRS voltages on electrocardiography in only 16% evaluable cases. Seventeen patients received implantable anti-arrhythmic devices. Median survival was 6.6 years following onset of symptoms and 3.4 years from diagnosis, and correlated with serum N-terminal prohormone brain natriuretic peptide (NT-proBNP) concentration and certain echocardiographic parameters at the latter. Orthotopic liver transplantation (OLT), performed to eliminate the predominant hepatic source of variant TTR T60A protein, was performed in eight patients including one who received a concomitant cardiac transplant. Cardiac amyloidosis progressed in all lone OLT recipients, of whom four died within 5 years.. Cardiac amyloidosis is almost always present at diagnosis in FAP T60A, and is a major determinant of its poor prognosis. Outcome of liver transplantation in FAP T60A has been discouraging.

Topics: Aged; Amyloid Neuropathies, Familial; Arrhythmias, Cardiac; Cardiomyopathies; Electrocardiography; Humans; Kaplan-Meier Estimate; Liver Transplantation; Middle Aged; Mutation; Natriuretic Peptide, Brain; Peptide Fragments; Phenotype; Prealbumin; Prospective Studies

The left ventricular (LV) scar size detected by cardiac magnetic resonance (CMR) imaging in ischemic cardiomyopathy (IC) has been correlated with mortality. However, the associations among myocardial fibrosis, ventricular geometry, and physiologic measures of myocardial performance remain to be defined. A retrospective analysis of patients with stable chronic IC (LV ejection fraction ≤50%) who underwent CMR imaging from 2004 to 2010 and had plasma B-type natriuretic peptide (BNP) measured within 14 days of the CMR study was undertaken. A total of 38 patients met the criteria (mean age 66 ± 10 years; 31 men [82%]). The duration of IC was 67 ± 69 months. The CMR characteristics included LV dilation (LV end-diastolic dimension 62 ± 8 mm) and severe systolic dysfunction (LV ejection fraction 28 ± 11%). The average quantitated myocardial fibrosis was 20 ± 12% of the LV mass. When stratified by fibrotic mass, increased myocardial scar size was associated with increased LV cavity size (p = 0.007), lower LV ejection fraction (p = 0.04), and higher BNP (p = 0.013). In comparison, when stratified by median BNP (475 pg/ml), an elevated BNP level was associated, not only with LV size, function, and degree of fibrosis, but also with increased meridional wall stress (p = 0.002) and worse New York Heart Association functional class (p = 0.006). In conclusion, in chronic IC, quantitated myocardial fibrosis is associated with CMR structural and functional LV abnormalities. Elevated BNP levels are related to high-risk structural and functional CMR abnormalities and wall stress and functional status. Myocardial fibrosis appears to be related to plasma BNP through the processes of ventricular remodeling.

Topics: Aged; Cardiomyopathies; Chronic Disease; Diagnosis, Differential; Disease Progression; Female; Fibrosis; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Severity of Illness Index; Ventricular Remodeling

In AL amyloidosis prognosis depends on the severity of heart dysfunction which is best assessed by natriuretic peptides (BNP and NT-proBNP). However, their clearance relies on glomerular filtration rate (GFR) and their concentration increases with renal failure. We evaluated the diagnostic and prognostic performance of NT-proBNP and BNP in 248 patients with AL amyloidosis with different degrees of renal failure. Patients were grouped according to GFR. Group 1 comprised 109 patients with GFR ≥60 mL/min/1.73 m(2) , Group 2, 77 subjects with GFR <60 and ≥15 mL/min/1.73 m(2) , and Group 3, 62 patients with GFR <15 mL/min/1.73 m(2) . The ability of natriuretic peptides to detect heart involvement and to predict survival in the three groups was assessed. Decreasing eGFR required higher cutoffs of both NT-proBNP and BNP for detecting heart involvement and predicting survival. Both natriuretic peptides were independent prognostic markers in Groups 1 and 2, whereas in Group 3 only BNP independently predicted survival. Natriuretic peptides are powerful and useful markers of cardiac dysfunction and prognosis, provided that eGFR is considered in interpreting their clinical meaning. BNP should be preferred in patients with end-stage renal failure.

Topics: Adult; Aged; Aged, 80 and over; Amyloid; Amyloidosis; Biomarkers; Cardiomyopathies; Confounding Factors, Epidemiologic; Female; Glomerular Filtration Rate; Heart; Humans; Kaplan-Meier Estimate; Kidney Failure, Chronic; Liver; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peripheral Nervous System; Peritoneal Dialysis; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Dialysis; ROC Curve

We evaluated ambulatory patients with Duchenne muscular dystrophy from the cardiovascular standpoint and studied the correlation between the results of electrocardiographic (ECG) findings, left ventricular ejection fraction (LVEF), troponin T and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patients' North Star Ambulatory Assessment scores.. Fifty patients of ages 6-12 (8.9 ± 2.8) were enrolled in this cross-sectional study. Cardiac evaluation included electrocardiography, echocardiography and cardiac enzyme tests.. North Star scores ranged from 6/34 to 34/34. Twenty-eight patients (56%) had ECG changes. The most frequently seen ECG abnormalities were short PR interval (14%, n= 7), right ventricular hypertrophy (16%, n= 8), prolonged QTc interval (10%, n= 5), prominent Q wave (10%, n= 5) and T wave inversion (44%, n= 22). In 10 patients (20%), LVEF was below 55%, troponin T and NT-proBNP levels were significantly elevated (P= 0.003 and P < 0.001, respectively). When North Star scores were compared to patients' age, enzyme levels, ECG and echocardiographic results, we discovered negative correlation with age (P < 0.001) and troponin T levels (P= 0.02) and positive correlation with LVEF (P= 0.02).. Patients with North Star scores of ≤16 are more at risk of developing cardiomyopathies. Troponin T is a cardiac index that can be used for evaluating myopathic patients and it seems to be correlated with the proBNP levels and LVEF values.

Topics: Arrhythmias, Cardiac; Cardiomyopathies; Child; Cross-Sectional Studies; Echocardiography; Electrocardiography; Humans; Male; Muscular Dystrophy, Duchenne; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Stroke Volume; Troponin T

The targeting of Ca(2+) cycling has emerged as a potential therapy for the treatment of severe heart failure. These approaches include gene therapy directed at overexpressing sarcoplasmic reticulum (SR) Ca(2+) ATPase, or ablation of phospholamban (PLN) and associated protein phosphatase 1 (PP1) protein complexes. We previously reported that PP1β, one of the PP1 catalytic subunits, predominantly suppresses Ca(2+) uptake in the SR among the three PP1 isoforms, thereby contributing to Ca(2+) downregulation in failing hearts. In the present study, we investigated whether heart-failure-inducible PP1β-inhibition by adeno-associated viral-9 (AAV9) vector mediated gene therapy is beneficial for preventing disease progression in genetic cardiomyopathic mice.. We created an adeno-associated virus 9 (AAV9) vector encoding PP1β short-hairpin RNA (shRNA) or negative control (NC) shRNA. A heart failure inducible gene expression system was employed using the B-type natriuretic protein (BNP) promoter conjugated to emerald-green fluorescence protein (EmGFP) and the shRNA sequence. AAV9 vectors (AAV9-BNP-EmGFP-PP1βshRNA and AAV9-BNP-EmGFP-NCshRNA) were injected into the tail vein (2×10(11) GC/mouse) of muscle LIM protein deficient mice (MLPKO), followed by serial analysis of echocardiography, hemodynamic measurement, biochemical and histological analysis at 3 months.. In the MLPKO mice, BNP promoter activity was shown to be increased by detecting both EmGFP expression and the induced reduction of PP1β by 25% in the myocardium. Inducible PP1βshRNA delivery preferentially ameliorated left ventricular diastolic function and mitigated adverse ventricular remodeling. PLN phosphorylation was significantly augmented in the AAV9-BNP-EmGFP-PP1βshRNA injected hearts compared with the AAV9-BNP-EmGFP-NCshRNA group. Furthermore, BNP production was reduced, and cardiac interstitial fibrosis was abrogated at 3 months.. Heart failure-inducible molecular targeting of PP1β has potential as a novel therapeutic strategy for heart failure.

Topics: Animals; Calcium Signaling; Calcium-Binding Proteins; Cardiomyopathies; Dependovirus; Gene Expression; Genetic Therapy; Genetic Vectors; Green Fluorescent Proteins; Heart Failure; Isoenzymes; Mice; Mice, Knockout; Myocardium; Natriuretic Peptide, Brain; Promoter Regions, Genetic; Protein Phosphatase 1; RNA, Small Interfering; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Ventricular Remodeling

Persistence of left ventricular (LV) systolic dysfunction after 6 months of diagnosis is believed to be a marker of an irreversible cardiomyopathy in peripartum cardiomyopathy (PPCM). We sought to determine the length of time required for recovery of LV systolic function (LVSF) in patients with PPCM.. Forty-two consecutive women with PPCM were enrolled in this prospective study. The minimum required time of follow-up for inclusion was 30 months. Each patient underwent transthoracic echocardiography, and plasma brain natriuretic peptide (BNP) and C-reactive protein measurement at admission, and every 3 months. Early recovery was defined as normalization of LVSF at 6 months post-diagnosis. Delayed recovery was defined if the length of time required for recovery of LVSF was longer than 6 months. Persistent left ventricular dysfunction (PLVD) was defined as an ejection fraction of <50% at the end of follow-up. Twenty patients (47.6%) recovered completely, 10 died (23.8%), and 12 (28.6%) had PLVD. Average time to complete recovery was 19.3 months after initial diagnosis (3-42 months). Early recovery was observed only in six patients (30%), whereas delayed recovery was observed in 14 out of 20 patients (70%). Patients with complete recovery were more likely to have a higher LV ejection fraction and smaller LV end-systolic dimensions at baseline.. Full recovery of LVSF in PPCM patients often requires longer than 6 months.

Topics: Adolescent; Adult; Analysis of Variance; Biomarkers; C-Reactive Protein; Cardiomyopathies; Female; Humans; Natriuretic Peptide, Brain; Pregnancy; Pregnancy Complications, Cardiovascular; Prospective Studies; Risk Factors; Stroke Volume; Time Factors; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left; Young Adult

The association between ongoing myocardial damage and outcomes in patients who have received an implantable cardioverter-defibrillator (ICD) is unclear.. Consecutive patients with cardiomyopathy, who had received an ICD (n = 107, mean age 65 ± 11 years), were prospectively enrolled. Myocardial membrane injury (heart-type fatty acid binding protein [H-FABP] >4.3 ng/mL) and myofibrillar injury (troponin T >0.01 ng/mL) were defined using receiver operating characteristic curves. Patients were followed for a median of 33.6 months, to an end point of appropriate ICD shock or cardiac death. Myocardial membrane injury (45%) and myofibrillar injury (41%) were equally prevalent among patients with cardiomyopathy who had received ICDs. Appropriate ICD shocks or cardiac death occurred in 31% and 15% of patients, respectively. Multivariate Cox regression analysis showed that serum H-FABP levels >4.3 ng/mL, but not troponin T levels, were a significant independent prognostic factor for cardiac events (hazard ratio 5.502, 95% confidence interval 1.705-17.75, P = .004). Subgroup analysis revealed that measuring H-FABP levels was valuable for anticipating event-free survival among patients with ICDs who were receiving amiodarone. High H-FABP levels also predicted subsequent outcomes in patients who had received ICDs for primary or secondary prevention.. Evaluating myocardial damage using H-FABP may be a promising tool for predicting outcomes in patients with cardiomyopathy who have received ICDs.

Topics: Adult; Aged; Aged, 80 and over; Amiodarone; Anti-Arrhythmia Agents; Atrial Fibrillation; Cardiomyopathies; Death, Sudden, Cardiac; Defibrillators, Implantable; Echocardiography; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Troponin T

Little is known about the effects of hypothermia on the cardiovascular system in term newborns with neonatal encephalopathy.. To evaluate whether mild hypothermia for neonatal encephalopathy is cardioprotective as indicated by the cardiac biomarkers cardiac troponin I (cTnI) and B-type natriuretic peptide (BNP).. This was an observational cohort study of infants treated for perinatal asphyxia. In infants, mild total body hypothermia treatment of 33.5°C during 72 h was initiated (n = 20). Samples of cTnI and BNP were collected before the start of hypothermia, at 24 and 48 h after birth, and after rewarming (84 h). BNP and cTnI values were then compared with BNP and cTnI values of asphyxiated infants not treated with hypothermia (n = 28).. No differences were found between the groups in clinical patient characteristics or inotropic support. The hypothermia-treated patients seemed to be clinically more affected (5-min Apgar score, p < 0.05; umbilical artery pH, p = 0.08), but showed similar encephalopathy scores. Significantly lower values for BNP were found in hypothermia- compared to nonhypothermia-treated infants at 48 h and at normothermia after rewarming [144 pmol/l (95-286) vs. 75 pmol/l (45-143), 182 pmol/l (73-341) vs. 43 pmol/l (24-163)]. No differences were found for cTnI concentrations between both groups.. The raised, but similar, cTnI values between hypothermia- and nonhypothermia-treated infants indicate similar myocardial damage in both groups. The lower BNP levels during hypothermia treatment suggest that hypothermia after perinatal asphyxia exerts a beneficial effect on cardiac function.

Topics: Adaptation, Physiological; Apgar Score; Asphyxia Neonatorum; Biomarkers; Cardiomyopathies; Cohort Studies; Female; Gestational Age; Heart; Hemodynamics; Humans; Hypothermia, Induced; Hypoxia-Ischemia, Brain; Infant, Newborn; Intensive Care Units, Neonatal; Male; Natriuretic Peptide, Brain; Troponin I

Assessment of plasma matrix metalloproteinase-9 (MMP-9) and Doppler markers of increased left ventricular (LV) filling pressure may be added to risk stratify patients with ischemic cardiomyopathy (IC). Therefore, we aimed at investigating the value of plasma MMP-9 and restrictive filling pattern (RFP) in IC patients.. Eighty-eight consecutive patients hospitalized for heart failure (LV ejection fraction ≤ 40%) due to IC were enrolled. A complete M-mode and two-dimensional echo-Doppler examination were performed. Patients were defined as having RFP if they had a mitral E wave deceleration time<150 ms. Plasma MMP-9 and N-terminal protype-B natriuretic peptide levels were assessed at the time of the index echocardiogram. The end point was all-cause mortality or hospitalization for worsening HF. Follow-up period was 25 ± 17 months.. Median value of MMP-9 was 714 ng/ml. On univariate analysis, a number of measurements predicted the composite end point: NYHA class>2, RFP, MMP-9>60.5 ng/ml, LV ejection fraction<27%, anemia, pulmonary pressure ≥ 35 mm Hg, N-terminal protype-B natriuretic peptide>1742 pg/ml, and glomerular filtration rate<60 ml/min/1.73 m(2). Independent variables of outcome were anemia (HR=1.9, p=0.031), and the combination of plasma MMP-9 and RFP (HR=3.2, p=0.004). On Kaplan-Meier survival curves, patients with elevated MMP-9 levels and RFP had the lowest event-free survival rate (log-rank: 29.0, p<0.0001). The net reclassification improvement showed a significant increase in the prediction model when elevated MMP-9 and RFP were added to the base model that included clinical, biochemical and echocardiographic parameters (p<0.0001).. MMP-9 levels and RFP have an incremental predictive value to risk classify IC patients.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiomyopathies; Disease-Free Survival; Echocardiography; Echocardiography, Doppler; Female; Heart Failure; Humans; Kaplan-Meier Estimate; Male; Matrix Metalloproteinase 9; Middle Aged; Mitral Valve; Myocardial Infarction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Assessment; Ventricular Dysfunction, Left; Ventricular Remodeling

Since early intervention using corticosteroids improves prognosis in some patients with cardiac sarcoidosis, early and accurate diagnosis of this clinical condition is important. However, it is still not easy to evaluate the activity of cardiac sarcoidosis in clinical practice. The aim of this study was to determine whether high-sensitive cardiac troponin T (hscTnT) is useful as an additional parameter to standard assessment in patients with cardiac sarcoidosis. Twelve patients who were diagnosed as having cardiac sarcoidosis at our institution were retrospectively studied. Evaluation of patients included clinical examinations, electrocardiography, echocardiography, 67-gallium-citrate (Ga) scintigraphy, 18F-fluoro2-deoxyglucose positron emission tomography (18F-FDG PET) and laboratory data including hs-cTnT, angiotensin-converting enzyme (ACE), lysozyme and B-type natriuretic peptide (BNP). The activity of cardiac sarcoidosis was judged mainly by using 18F-FDG PET. Localized uptake of 18F-FDG, which was considered to be active cardiac sarcoidosis, was seen in 8 patients. Based on the findings of 18F-FDG PET, hs-cTnT was considered to be a reliable parameter: sensitivity and specificity were 87.5% and 75.0%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) were 87.5% and 75.0%, respectively. On the other hand, these values in lysozyme and BNP markers were not as high as those in hs-cTnT. Although an ACE marker and Ga-67 scintigraphy showed specificity and PPV of 100%, both sensitivity and NPV were less than 50%. Furthermore, hs-cTnT levels decreased after steroid therapy in some patients. Hs-cTnT seems to be a useful marker for evaluating the activity of cardiac sarcoidosis.

Topics: Aged; Biomarkers; Cardiomyopathies; Echocardiography; Electrocardiography; Female; Fluorodeoxyglucose F18; Glucocorticoids; Humans; Male; Middle Aged; Muramidase; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Positron-Emission Tomography; Predictive Value of Tests; Retrospective Studies; Sarcoidosis; Sensitivity and Specificity; Stroke Volume; Troponin T; Ventricular Function, Left

Insulin resistance (IR) is part of the metabolic syndrome (Mets) that develops after lifestyle changes and obesity. Although the association between Mets and myocardial injury is well known, the effect of IR on myocardial damage remains unclear.. We studied 2200 normal subjects who participated in a community-based health check in the town of Takahata in northern Japan. The presence of IR was assessed by homeostasis model assessment ratio, and the serum level of heart-type fatty acid binding protein (H-FABP) was measured as a maker of silent and ongoing myocardial damage. H-FABP levels were significantly higher in subjects with IR and Mets than in those without metabolic disorder regardless of gender. Multivariate logistic analysis showed that the presence of IR was independently associated with latent myocardial damage (odds ratio: 1.574, 95% confidence interval 1.1-2.3) similar to the presence of Mets.. In a screening of healthy subjects, IR and Mets were similarly related to higher H-FABP levels, suggesting that there may be an asymptomatic population in the early stages of metabolic disorder that is exposed to myocardial damage and might be susceptible to silent heart failure.

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathies; Cross-Sectional Studies; Early Diagnosis; Fatty Acid Binding Protein 3; Fatty Acid-Binding Proteins; Female; Humans; Hypertension; Incidence; Insulin Resistance; Japan; Male; Mass Screening; Metabolic Syndrome; Middle Aged; Natriuretic Peptide, Brain; Sex Characteristics

Asymmetric dimethylarginine (ADMA) is associated with increased mortality in patients with chronic heart failure but it remains unclear if the etiology of heart failure influences the prognostic value of dimethylarginines.. L-Arginine, ADMA, and symmetric dimethylarginine (SDMA) were measured by liquid chromatography-tandem mass spectrometry in 341 patients with chronic heart failure due to dilated cardiomyopathy (DCM; n = 226) or ischemic cardiomyopathy (ICM; n = 115). Median (interquartile range [IQR]) ADMA and SDMA plasma levels were higher, L-arginine and the L-arginine-ADMA ratio were lower in patients with severe forms of heart failure (New York Heart Association (NYHA) functional class III or IV) compared with milder forms (NYHA functional class I or II) (ADMA 0.57 (0.14) μmol/L vs 0.54 (0.12) μmol/L [P < .001]; SDMA 0.47 (0.27) μmol/L vs 0.37 (0.13) μmol/L [P < .001]; L-arginine 81.8 (39.1) μmol/L vs 92.6 (39.3) μmol/L [P < .01]), but no significant differences were observed between the different etiologies. The L-arginine-ADMA ratio was associated with outcome only in patients with DCM. In multivariate analysis, the mortality risk of DCM patients was significantly lower for those in the highest quartile compared with the lowest quartile during a median observation time of 3.3 years (hazard ratio 0.31, 95% CI 0.11-0.88; P = .028, adjusted for other risk factors).. DCM patients with unfavourable L-arginine-ADMA ratio are at increased risk for death.

Topics: Arginine; Biomarkers; Cardiomyopathies; Cardiomyopathy, Dilated; Chromatography, Liquid; Creatinine; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Severity of Illness Index; Tandem Mass Spectrometry

A 65-year-old woman presenting with cardiac sarcoidosis underwent serial measurement of her serum high-sensitivity cardiac troponin I (Hs-cTnI) and N-terminal proB-type natriuretic peptide (NT-proBNP) concentrations. She was treated with 1,000 mg/day methylprednisolone for 2 days, which was subsequently replaced by 30 mg/day prednisolone, and decreased to 20 mg/day at the time of discharge, 2 months later. Her echocardiogram showed improvements in the left ventricular systolic and diastolic function, along with a decrease in the concentration of Hs-cTnI and NT-proBNP. This is the first report suggesting that Hs-cTnI might be a reliable means of assessing the effects of treatment of cardiac sarcoidosis.

Topics: Aged; Cardiomyopathies; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Sarcoidosis; Troponin I

Recent reports provide indirect evidence of myocardial injury and ventricular dysfunction after prolonged exercise. However, existing data is conflicting and lacks direct verification of functional myocardial alterations by CMR [cardiac MR (magnetic resonance)]. The present study sought to examine structural myocardial damage and modification of LV (left ventricular) wall motion by CMR imaging directly after a marathon. Analysis of cTnT (cardiac troponin T) and NT-proBNP (N-terminal pro-brain natriuretic peptide) serum levels, echocardiography [pulsed-wave and TD (tissue Doppler)] and CMR were performed before and after amateur marathon races in 28 healthy males aged 41 ± 5 years. CMR included LGE (late gadolinium enhancement) and myocardial tagging to assess myocardial injury and ventricular motion patterns. Echocardiography indicated alterations of diastolic filling [decrease in E/A (early transmitral diastolic filling velocity/late transmitral diastolic filling velocity) ratio and E' (tissue Doppler early transmitral diastolic filling velocity)] postmarathon. All participants had a significant increase in NT-proBNP and/or cTnT levels. However, we found no evidence of LV LGE. MR tagging demonstrated unaltered radial shortening, circumferential and longitudinal strain. Myocardial rotation analysis, however, revealed an increase of maximal torsion by 18.3% (13.1 ± 3.8 to 15.5 ± 3.6 °; P=0.002) and maximal torsion velocity by 35% (6.8 ± 1.6 to 9.2 ± 2.5 °·s-1; P<0.001). Apical rotation velocity during diastolic filling was increased by 1.23 ± 0.33 °·s-1 after marathon (P<0.001) in a multivariate analysis adjusted for heart rate, whereas peak untwist rate showed no relevant changes. Although marathon running leads to a transient increase of cardiac biomarkers, no detectable myocardial necrosis was observed as evidenced by LGE MRI (MR imaging). Endurance exercise induces an augmented systolic wringing motion of the myocardium and increased diastolic filling velocities. The stress of marathon running seems to be better described as a burden of myocardial overstimulation rather than cardiac injury.

Topics: Adult; Biomarkers; Cardiomyopathies; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Running; Torsion Abnormality; Troponin T; Ventricular Dysfunction, Left

There are few experimental models of heart failure (HF) in large animals, despite structural and functional similarities to human myocardium. We have developed a porcine model of chronic tachycardia-induced cardiomyopathy.. Homogenous siblings of White Large breed swine (n=6) underwent continuous right ventricular (RV) pacing at 170 bpm; 2 subjects served as controls. In the course of RV pacing, animals developed a clinical picture of HF and were presented for euthanasia at subsequent stages: mild, moderate and end-stage HF. Left ventricle (LV) sections were analyzed histologically and relative ANP, BNP, phospholamban and sarcoplasmic reticulum calcium ATPase 2a transcript levels in LV were quantified by real time RT-PCR.. In the course of RV pacing, animals demonstrated reduced exercise capacity (time of running until being dyspnoeic: 6.6 ± 0.5 vs. 2.4 ± 1.4 min), LV dilatation (LVEDD: 4.9 ± 0.4 vs. 6.7 ± 0.4 cm), impaired LV systolic function (LVEF: 69 ± 8 vs. 32 ± 7 %), (all baseline vs. before euthanasia, all p<0.001). LV tissues from animals with moderate and end-stage HF demonstrated local foci of interstitial fibrosis, congestion, cardiomyocyte hypertrophy and atrophy, which was not detected in controls and mild HF animals. The up-regulation of ANP and BNP and a reduction in a ratio of sarcoplasmic reticulum calcium ATPase 2a and phospholamban in failing myocardium were observed as compared to controls.. In pigs, chronic RV pacing at relatively low rate can be used as an experimental model of HF, as it results in a gradual deterioration of exercise tolerance accompanied by myocardial remodeling confirmed at subcellular level.

Topics: Animals; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiomyopathies; Chronic Disease; Disease Models, Animal; Exercise Test; Female; Natriuretic Peptide, Brain; Random Allocation; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Swine; Tachycardia

Cirrhotic cardiomyopathy may appear following liver transplantation. Brain-natriuretic peptide (BNP) values exceeding 391 pg/ml or 567 pg/ml may partially reflect ventricular stress because of cardiac dysfunction or indicate cirrhotic cardiomyopathy, respectively. The aim of the study was to assess cardiac dysfunction in liver transplant patients and its correlation with BNP as a biomarker. From 1/2008 to 7/2009, 157 adult liver transplant recipients with proven cirrhosis were recruited for the study. BNP and liver enzymes were recorded upon admission, on the first postoperative day (POD) and 1 week after transplantation. Patients with ischemic heart attacks were excluded from the study. We identified two groups of patients. Group 1 was characterized by a BNP <391 pg/ml and Group 2 by a BNP >391 pg/ml. Group 2 had a significantly higher model of end-stage liver disease score than Group 1 (median 30, range 10-40 versus median 22, range 10-40, respectively; P = 0.003), required significantly more dialysis treatments and had a significantly higher mortality rate. Postoperative echocardiography in patients with a BNP >391 pg/ml indicated diastolic dysfunction in all of the patients and systolic dysfunction in 10 of the patients. Increased serum-BNP was associated with an overall higher mortality rate.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Critical Care; Diastole; Echocardiography; Female; Fibrosis; Humans; Liver Transplantation; Male; Middle Aged; Myocardial Infarction; Natriuretic Peptide, Brain; Systole

To determine plasma B-type natriuretic peptide (BNP) levels in children with heart diseases before medical or surgical treatment for monitoring therapeutic efficacy in an observational prospective clinical trial at tertiary care centre.. In 522 paediatric patients at an age of 6.4 ± 5.2 years (mean ± SD; range: 14 days-18 years) with congenital heart disease (CHD), cardiomyopathies (CMP) or pulmonary arterial hypertension (PAH), plasma BNP levels were evaluated before and under treatment.. Most types of heart disease are associated with increased mean plasma BNP levels before treatment, with highest values in children with CMP (BNP 6165 pg/mL in dilated CMP vs. 817 pg/mL in hypertrophic, vs. 1236 pg/mL in restrictive CMP, each p < 0.05). Children with PAH showed a significant decrease in BNP levels under medical treatment (mean BNP 981 pg/mL before vs. 26 pg/mL under treatment, p < 0.05). Children with univentricular CHD undergoing surgical staged palliation showed a significant decrease in BNP levels after bidirectional cavopulmonary anastomosis (BDCP) (BNP 109 pg/mL before vs. 70 pg/mL after BDCP, p < 0.05).. Plasma BNP levels are elevated in children with heart disease before treatment and are a useful laboratory parameter under treatment during long-term follow-up.

Topics: Adolescent; Cardiomyopathies; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Ventricles; Hemodynamics; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Male; Natriuretic Peptide, Brain; Prospective Studies; Statistics as Topic; Statistics, Nonparametric

When heart failure and tachycardia occur simultaneously, a useful diagnostic tool for early discrimination of patients with benign tachycardia-mediated cardiomyopathy (TMC) versus major structural heart disease (MSHD) is not available. Such a tool is required to prevent unnecessary and wearing diagnostics in patients with reversible TMC. Moreover, it could lead to early additional diagnostics and therapeutic approaches in patients with MSHD.. A total of 387 consecutive patients with supraventricular arrhythmia underwent assessment at a single center. Of these patients, 40 fulfilled the inclusion criteria with a resting heart rate ≥100 bpm and an impaired left ventricular ejection fraction <40%. In all patients, successful electrical cardioversion was performed. At baseline, day 1 and weekly for 4 weeks, levels of NT-proBNP and echocardiographic parameters were evaluated. An NT-proBNP ratio (BNP-R) was calculated as a quotient of baseline NT-proBNP/follow-up NT-proBNP. After 4 weeks, cardiac catheterization was performed to identify patients with a final diagnosis of TMC versus MSHD.. Initial NT-proBNP concentrations were elevated and consecutively decreased after cardioversion in all patients. Multivariate regression and ROC analysis revealed that BNP-R discriminated between patients with TMC versus MSHD independent and superior to all other variables. The area under the ROC curve for BNP-R to detect TMC was 0.90 (95% CI 0.79-1.00; p < 0.001) after 1 week and 0.995 (95% CI 0.99-1.00; p < 0.0001) after 4 weeks. One week after cardioversion already, a BNP-R cutoff ≥2.3 was useful for TMC diagnosis indicated by an accuracy of 90%, sensitivity of 84% and specificity of 95%.. BNP-R was found to be highly accurate for the early diagnosis of TMC.

Topics: Aged; Biomarkers; Cardiac Catheterization; Cardiomyopathies; Early Diagnosis; Echocardiography, Doppler; Electric Countershock; Exercise Test; Female; Germany; Heart Failure; Heart Rate; Humans; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pilot Projects; Predictive Value of Tests; Recovery of Function; ROC Curve; Stroke Volume; Tachycardia, Supraventricular; Time Factors; Treatment Outcome; Ventricular Function, Left

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Cardiomyopathies; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Risk Factors

Paediatric cardiomyopathy and heart failure are distinct but frequently associated conditions, which have a high mortality. Traditional medical therapy has evolved to incorporate newer classes of heart failure drugs, although the evidence to support efficacy in children is limited. This perspective article discusses the rationale, benefits and limitations of the various classes of drug therapy used in paediatric heart failure due to cardiomyopathy or congenital heart disease. Controversies in management and challenges for future development are highlighted.

Topics: Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Cardiomyopathies; Cardiotonic Agents; Child; Digoxin; Diuretics; Heart Defects, Congenital; Heart Failure; Humans; Hydrazones; Natriuretic Peptide, Brain; Pyridazines; Simendan

Spontaneously hypertensive heart failure rats (SHHFs) take longer to develop compensated heart failure (HF) and congestive decompensation than common surgical models of HF. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loading in hypertensive rats induces cardiac fibrosis, hypertrophy, and--in a minority-congestive HF. By combining ISO with dietary salt loading in young SHHFs, the authors sought a nonsurgical model that is more time--and resource-efficient than any of these factors alone. The authors hypothesized that salt loading would enhance ISO-accelerated cardiomyopathy, promoting fibrosis, hypertrophy, and biochemical characteristics of HF. SHHFs (lean male, 90d) were infused for 4 wk with ISO (2.5 mg/kg/day) or saline. After 2 wk of infusion, a 6-wk high-salt diet (4%, 6%, or 8% NaCl) was initiated. Eight percent salt increased heart weight, HF markers (plasma B-type natriuretic peptide, IL-6), lung lymphocytes, and indicators of lung injury and edema (albumin and protein) relative to control diet, while increasing urine pro-atrial natriuretic peptide relative to ISO-only. High salt also exacerbated ISO-cardiomyopathy and fibrosis. Thus, combining ISO infusion with dietary salt loading in SHHFs holds promise for a new rat HF model that may help researchers to elucidate HF mechanisms and unearth effective treatments.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Bronchoalveolar Lavage Fluid; Cardiomyopathies; Fibrosis; Heart; Heart Failure; Interleukin-6; Isoproterenol; Male; Natriuretic Peptide, Brain; Rats; Rats, Inbred SHR; Sodium Chloride, Dietary

As there is no method to detect trastuzumab-related cardiotoxicity (TRC) preclinically, patients are monitored with serial assessments of left ventricular ejection fraction (LVEF) with instigation of cardiac therapy and possible interruption of trastuzumab therapy if TRC develops. Serum cardiac biomarkers, including troponins and natriuretic peptides, represent possible tools to detect cardiotoxicity at a preclinical level.. We sought biochemical evidence of cardiac damage or strain in a cohort of women already receiving trastuzumab by performing a cross-sectional study of serum cardiac biomarkers. All patients had a normal LVEF and no clinical evidence of cardiac failure. Serum troponin I and N-terminal pro-B type natriuretic peptide (NT pro-BNP) were assayed immediately prior to trastuzumab infusion (t0; n = 36) and 24 hours later (t24; n = 31).. Troponin I was not elevated in any patient at t0 or t24. Overall 14/36 (39%) patients had at least one NT pro-BNP level above the upper limit of normal (ULN) and both levels were above the ULN in 8/31 (26%) patients. There was no significant change in NT pro-BNP from t0 to t24.. NT pro-BNP levels are elevated in a significant proportion of patients with normal LVEF receiving trastuzumab. Troponin I levels are not raised in this group, perhaps reflecting the mechanism of cardiotoxicity. The data provide biochemical evidence of subclinical cardiac strain in women receiving trastuzumab. Results are exploratory and have informed the design of a larger study examining the predictive utility of serial serum NT pro-BNP levels for TRC in the adjuvant setting.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cohort Studies; Cross-Sectional Studies; Female; Heart Function Tests; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab; Troponin I

During the past 3 years, seven potential candidates for mechanical circulatory support (MCS) were treated at our center. Ultimately, only one of them needed MCS (extracorporeal membrane oxygenation [ECMO] for 16 days), although 5 years earlier, all would have been considered for MCS at our center. Seven consecutive patients were seen in this period: four toddlers (three suffering from fulminant myocarditis and one with dilated cardiomyopathy associated with spongy myocardium) and three adolescents (two with postmyocarditis cardiomyopathy and one with hypertrophic cardiomyopathy and severe restrictive dysfunction after an ischemic event with cardiopulmonary resuscitation [stunned heart]). All patients presented in acute cardiocirculatory decompensation. All were admitted to the intensive care unit (ICU); all but one were sedated and intubated. A combination of levosimendan, milrinone, and nesiritide was administered to all patients. Use of catecholamines was kept short (<48 h in six individuals). MCS (ECMO, Berlin Heart Excor Pediatric, and Heartware) was always available. MCS initiation was indicated in only one patient, who was developing progressive multiorgan failure (MOF). The three toddlers with myocarditis recovered with complete normalization of myocardial function within 6 months. The fourth toddler is still at the ICU while waiting for transplantation. The three adolescents were listed with high urgency for heart transplantation, and all received a graft within 3 weeks. The adolescent with the stunned heart developed progressive MOF and was successfully supported with ECMO until transplantation. All six patients with completed course were discharged home in New York Heart Association Heart Failure Functional Classification System I condition without neurological deficits. Combined use of levosimendan, milrinone, and nesiritide, avoidance of catecholamines as much as possible, and MCS as backup are the new strategies at our center. This cardioprotective approach gives excellent outcome at lower risk and better cost-effectiveness in our pediatric patients with acute heart failure. Pediatric trials are recommended to evaluate combined use of newer cardioprotective drugs.

Topics: Adolescent; Cardiomyopathies; Cardiotonic Agents; Catecholamines; Child, Preschool; Extracorporeal Membrane Oxygenation; Female; Heart Failure; Humans; Hydrazones; Infant; Male; Milrinone; Myocarditis; Natriuretic Agents; Natriuretic Peptide, Brain; Pyridazines; Simendan

Available information regarding clozapine-related cardiomyopathy is limited to reports of severe left ventricular dysfunction not rarely with fatal clinical evolution. A subclinical cardiotoxic effect might be diagnosed using echocardiography and N-terminal pro-B-type natriuretic peptide assay.. Thirty-eight patients with psychotic disorder in chronic therapy with clozapine (24 male and 14 female subjects; mean age, 38.4 years) were enrolled. Left ventricular ejection fraction (LVEF) was measured by area-length method (average of 5 measurements).. Twelve patients showed a mild depression of left ventricular function (LVEF between 50% and 55%), 2 LVEF less than 50% and 1 less than 30%. The area under the receiver operating characteristic curve for N-terminal pro-B-type natriuretic peptide as a predictor of left ventricular dysfunction was 0.87.. A subclinical left ventricular dysfunction was found in 3 of 38 patients, whereas a mild impairment of the left ventricular systolic function occurred in 1 of 3 of young, previously healthy, clozapine-treated patients A prospective study in clozapine-naive patients may be useful to better understand cardiotoxic effects of clozapine.

Topics: Adult; Antipsychotic Agents; Biomarkers; Cardiomyopathies; Clozapine; Female; Humans; Male; Mental Disorders; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Ultrasonography; Ventricular Dysfunction, Left

The inactive N-terminal fragment of B-type natriuretic peptide is a strong predictor of mortality among patients with acute and chronic heart failure secondary to ischaemic heart disease. Its prognostic utility in patients with non-ischaemic heart disease is not well established. We therefore assessed the relationship of N-terminal proBNP levels and long-term mortality in patients with non-ischaemic cardiomyopathy.. N-terminal proBNP was measured in serum samples of 156 patients who presented to a single academic centre with worsening heart failure secondary to non-ischaemic cardiomyopathy. The rate of death from all causes was determined after a mean follow-up of 8.9 years.. Multivariate analyses, using Cox proportional hazards models, established NT-proBNP and left ventricular diastolic diameter as predictors for cardiac mortality with estimated hazard ratios of 2.76 (95% confidence interval: 1.53, 4.98) and 1.06 (95% confidence interval: 1.02, 1.10), respectively.. This to date longest-term analysis of N-terminal proBNP and mortality in patients with proven non-ischaemic cardiomyopathy confirms this cardiac-specific biomarker as powerful, independent risk predictor. It is a superior prognostic determinant to New York Heart Association functional class and left ventricular ejection fraction.

Topics: Biomarkers; Cardiomyopathies; Comorbidity; Female; Germany; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Reproducibility of Results; Risk Assessment; Risk Factors; Sensitivity and Specificity; Survival Analysis; Survival Rate; Ventricular Dysfunction, Left

Uremic cardiomyopathy contributes substantially to mortality in chronic kidney disease (CKD) patients. Glucagon-like peptide-1 (GLP-1) may improve cardiac function, but is mainly degraded by dipeptidyl peptidase-4 (DPP-4).. In a rat model of chronic renal failure, 5/6-nephrectomized [5/6N] rats were treated orally with DPP-4 inhibitors (linagliptin, sitagliptin, alogliptin) or placebo once daily for 4 days from 8 weeks after surgery, to identify the most appropriate treatment for cardiac dysfunction associated with CKD. Linagliptin showed no significant change in blood level AUC(0-∞) in 5/6N rats, but sitagliptin and alogliptin had significantly higher AUC(0-∞) values; 41% and 28% (p = 0.0001 and p = 0.0324), respectively. No correlation of markers of renal tubular and glomerular function with AUC was observed for linagliptin, which required no dose adjustment in uremic rats. Linagliptin 7 µmol/kg caused a 2-fold increase in GLP-1 (AUC 201.0 ng/l*h) in 5/6N rats compared with sham-treated rats (AUC 108.6 ng/l*h) (p = 0.01). The mRNA levels of heart tissue fibrosis markers were all significantly increased in 5/6N vs control rats and reduced/normalized by linagliptin.. DPP-4 inhibition increases plasma GLP-1 levels, particularly in uremia, and reduces expression of cardiac mRNA levels of matrix proteins and B-type natriuretic peptides (BNP). Linagliptin may offer a unique approach for treating uremic cardiomyopathy in CKD patients, with no need for dose-adjustment.

Topics: Animals; Area Under Curve; Cardiomyopathies; Dipeptidyl Peptidase 4; Dipeptidyl-Peptidase IV Inhibitors; Disease Models, Animal; Gene Expression Regulation; Glomerular Filtration Rate; Glucagon-Like Peptide 1; Heart; Humans; Kidney Failure, Chronic; Linagliptin; Myocardium; Natriuretic Peptide, Brain; Nephrectomy; Piperidines; Purines; Pyrazines; Quinazolines; Rats; Reverse Transcriptase Polymerase Chain Reaction; Sitagliptin Phosphate; Triazoles; Uracil; Uremia

Cardiac disease is a significant complication of childhood oncologic therapy. We report the case of a 14-year-old female with acute promyelocytic leukemia who developed symptomatic cardiomyopathy only 4 months into treatment with a combination of daunomycin and all-trans retinoic acid (ATRA). Despite cessation of daunomycin, she demonstrated fluctuating systolic function in relation to ATRA administration. Improvement and deterioration in systolic function on echocardiogram and serum B-natriuretic peptide levels were seen while receiving ATRA 1 week on and 1 week off, respectively, during the maintenance phase of therapy.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Chronic Disease; Daunorubicin; Female; Humans; Leukemia, Promyelocytic, Acute; Natriuretic Peptide, Brain; Tretinoin

To study the effect of dexrazoxane in preventing doxorubicin-induced cardiotoxicity in rabbit-models and its mechanism.. Thirty one New Zealand white rabbits were randomly divided into two groups, doxorubicin (DOX) group and doxorubicin + dexrazoxane group. The cardiotoxicity was assessed by measuring serum superoxide dismutase (SOD), malondialdehyde (MDA), cardiac troponin I (cTnI), brain natriuretic peptide (BNP), left ventricular ejection function (LVEF), and left ventricular fractional shortening (LVFS), before and 4 and 10 weeks after intervention. Pathological changes in cardiac tissues and the apoptosis of myocardial cells were examined at the end of the experiment. Results Doxorubicin increased serum MDA, cTnI and BNP and decreased SOD, LVEF and LVFS (P < 0.05). Dexrazoxane (DEX) inhibited the increase of MDA, cTnI and BNP, and the decrease of LVEF and LVFS (P < 0.05). The rabbits treated with doxorubicin + dexrazoxane had slighter pathological changes in myocardium and apoptotic myocardial cells than those treated with DOX.. Dexrazoxane prevents doxorubicin-induced cardiotoxicity through decreasing oxygen free radical production, cutting down lipid peroxidation, and depressing cardiocyte apoptosis.

Topics: Animals; Apoptosis; Cardiomyopathies; Cyclooctanes; Doxorubicin; Female; Lignans; Lipid Peroxidation; Male; Natriuretic Peptide, Brain; Polycyclic Compounds; Rabbits; Random Allocation; Reactive Oxygen Species; Schisandraceae; Superoxide Dismutase; Troponin I

A case of cardiomyopathy and ventricular tachycardia previously assumed to be idiopathic in origin is described. Investigation with cardiac magnetic resonance imaging prompted the diagnosis and successful treatment of an underlying disorder based on typical scarring patterns seen with late gadolinium enhancement. The present report suggests that clinicians should have a low threshold for actively excluding this condition in patients presenting with cardiomyopathy, even in the absence of other disease features, particularly if typical scarring patterns are found on cardiac magnetic resonance imaging because disease-specific therapy appears to significantly improve both symptoms and prognosis.

Topics: alpha-Galactosidase; Cardiomyopathies; Enzyme Replacement Therapy; Fabry Disease; Heart Ventricles; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Tachycardia, Ventricular

To investigate the changes and the clinical significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) and glycogen phosphorylase isoenzyme BB (GPBB) levels in neonates with asphyxia complicated by myocardial injury.. Sixty-four neonates with asphyxia (39 mild, 25 severe) were enrolled. Of the 64 neonates, 30 had myocardial injury and 34 did not develop myocardial injury. Twenty-five healthy neonates served as a control group. Plasma levels of NT-proBNP and GPBB were measured using ELISA. Myocardial enzymes and cardiac troponin I were stimultaneously measured, and electrocardiography and chest radiographs were obtained.. The plasma levels of NT-proBNP and GPBB in neonates with myocardial injury were significantly higher than those in neonates without myocardial injury and in the control group (P<0.01). The neonates with severe asphyxia had significantly increased plasma NT-proBNP and GPBB concentrations compared to those with mild asphyxia and the control group (P<0.01). Spearman rank correlation analysis showed that plasma NT-proBNP level was positively correlated with plasma GPBB level in neonates with asphyxia. Plasma levels of NT-proBNP and GPBB were also positively correlated with plasma levels of CK-MB, CK and LDH (P<0.01).. Both NT-proBNP and GPBB can be used as biomarkers of myocardial injury in neonates with asphyxia. The measurement of plasma NT-proBNP and GPBB levels was useful in early identification of myocardial injury and severity evaluation in neonates with asphyxia.

Topics: Asphyxia Neonatorum; Cardiomyopathies; Creatine Kinase, MB Form; Enzyme-Linked Immunosorbent Assay; Female; Glycogen Phosphorylase; Humans; Infant, Newborn; Male; Natriuretic Peptide, Brain; Peptide Fragments

The ability of serum B-type natriuretic peptide levels (BNP) to predict outcomes in children with heart failure (HF) has not been well demonstrated. This study was designed to determine whether BNP levels predict outcomes in patients with moderate symptomatic HF.. We investigated whether enrollment BNP levels for the Pediatric Carvedilol Trial were associated with baseline characteristics. Freedom from a composite end point of HF hospitalization, death, or transplantation at 9 months was compared using a threshold BNP level identified using receiver operating curve analysis. Median BNP level was 110 pg/mL (interquartile range, 22.4 to 342.0 pg/mL) in 138 subjects. Median age was 3.4 years (interquartile range, 1.1 to 11.0 years). Diagnoses were cardiomyopathy (60%) and congenital heart disease (40%); 73% had a systemic left ventricle. BNP levels correlated moderately with left ventricular ejection fraction (R=0.39, P<0.001) but did not differ by HF class, age, diagnosis, sex, ventricular morphology, or left ventricular end-diastolic dimension Z-score (R=0.19). Outcome events included 25 HF hospitalizations, 4 deaths, and 2 transplants. Sensitivity was 71% and specificity 63%, for a BNP cutoff value of 140 pg/mL. BNP ≥140 pg/mL (hazard ratio, 3.7; 95% confidence interval, 1.62 to 8.4; P=0.002) and age >2 years (hazard ratio, 4.45; 95% confidence interval, 1.68 to 12.04; P=0.003) were independently associated with worse outcomes.. In children with moderately symptomatic HF, BNP ≥140 pg/mL and age >2 years identified subjects at higher risk for worse outcome. Further validation is needed to determine the BNP levels necessary to stratify risk in other pediatric cohorts.

Topics: Adrenergic beta-Antagonists; Age Factors; Biomarkers; Carbazoles; Cardiomyopathies; Carvedilol; Chi-Square Distribution; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Failure; Humans; Infant; Male; Multicenter Studies as Topic; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Propanolamines; Proportional Hazards Models; Randomized Controlled Trials as Topic; Risk Factors; Sensitivity and Specificity; Statistics, Nonparametric; Treatment Outcome

To test the diagnostic performance of BNP and NT-ProBNP in children with different hemodynamic dysfunctions.. Seventy children who underwent echocardiography and were classified into left and right ventricle volume and pressure overload (LVvO, LVpO, RVvO, and RVpO, respectively) and biventricular volume overload (BVvO) were enrolled.. BNP and NT-ProBNP levels in all groups were higher than those in the control group (p<0.001, p<0.001). The increase in peptide levels was strongly correlated with the severity of heart failure (p<0.001, p<0.001). There was no significant difference in peptide levels in-between LVvO, LVpO, RVvO, RVpO and BVvO groups. Both measurements were significantly correlated (r=0.76, p<0.001) with each other. NT-ProBNP showed a high sensitivity, whereas BNP showed a high specificity and accuracy. AUCs in ROC-curve were 0.97 for BNP and 0.96 for NT-ProBNP.. NT-ProBNP may be used in screening of risk groups for cardiac failure because of its' higher sensitivity, but BNP may be specifically used in monitoring patients with heart failure.

Topics: Adolescent; Cardiac Volume; Cardiomyopathies; Child; Child, Preschool; Female; Heart Defects, Congenital; Heart Failure; Humans; Infant; Male; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Sensitivity and Specificity

We sought to evaluate amniotic fluid brain natriuretic peptide (BNP) levels as a biomarker of recipient twin (RT) cardiomyopathy (RTCM) in twin-twin transfusion syndrome.. Amniotic fluid samples were obtained from 157 twin-twin transfusion syndrome RTs and from 6 singletons (controls) from 2007 through 2009. N-terminal prohormone BNP (NT-proBNP) levels were quantified by enzyme-linked immunosorbent assay. RTCM was classified as mild (IIIA), moderate (IIIB), or severe (IIIC) by fetal echocardiography. The relationship between NT-proBNP and RTCM was evaluated using analysis of variance. The ability of NT-proBNP to predict moderate or greater RTCM was evaluated by receiver operating characteristic analysis.. There is a significant positive correlation between NT-proBNP levels and worsening RTCM (r = 0.33; P < .001). NT-proBNP thresholds of 569 fmol/mg and 369 fmol/mg had a sensitivity of 70% and 87%, and specificity of 67% and 42%, respectively, in predicting moderate or greater RTCM.. This is the first large case series that demonstrates a relationship between NT-proBNP and RTCM. This pathophysiologic insight supports ongoing efforts to develop screening biomarkers.

Topics: Adult; Amniotic Fluid; Biomarkers; Blood Flow Velocity; Cardiomyopathies; Case-Control Studies; Enzyme-Linked Immunosorbent Assay; Female; Fetofetal Transfusion; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Retrospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Ultrasonography, Doppler; Umbilical Veins

Cardiac involvement is one of the most important prognostic factors in systemic AL amyloidosis. The aim of our study was to assess the role of cardiovascular magnetic resonance (CMR) imaging in prognosis evaluation in AL amyloidosis.. We retrospectively analyzed 29 consecutive patients with AL amyloidosis who had undergone CMR. Clinical, laboratory, echocardiographic, and CMR characteristics were compared between CMR-positive (ie, with CMR signs of cardiac localization of AL amyloidosis) and CMR-negative patients. Univariate and multivariate analyses were performed to assess the prognostic value of positive CMR in comparison with other prognostic factors.. CMR was positive in 11 patients (38%). The overall survival rates for CMR-positive patients were 28%, 14%, and 14% versus 84%, 77%, and 45% at 1, 2, and 5 years, respectively, for CMR-negative patients (P=.002). Late gadolinium enhancement patterns, biventricular hypertrophy, and pericardial effusion on CMR were more frequent in nonsurvivors. Congestive heart failure, abnormal echocardiography, Eastern Cooperative Oncology Group grade >1, brain natriuretic peptide, and left ventricular ejection fraction <55% also were associated with a decreased survival. The presence of congestive heart failure was the only significant variable associated with survival on multivariate analysis.. We found that the presence of a positive CMR in AL amyloidosis was associated with a significantly increased risk of death, in particular of cardiac origin, but was not independent of clinical congestive heart failure.

Topics: Adult; Aged; Aged, 80 and over; Amyloidosis; Analysis of Variance; Biomarkers; Cardiomyopathies; Echocardiography; Female; France; Gadolinium; Heart Failure; Humans; Kaplan-Meier Estimate; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Proportional Hazards Models; Retrospective Studies; Stroke Volume

Peripartum cardiomyopathy (PPCM) is a form of heart failure that occurs in women within 1 month before delivery and 5 months after delivery. The outcome of PPCM is variable but improves significantly when appropriate medication is administered in the acute phase; furthermore, the outcome does not worsen even after discontinuation of therapy in the chronic phase. The symptoms and signs of PPCM are similar to those of idiopathic dilated cardiomyopathy. The medical management of patients with PPCM is similar to that for other other forms of heart failure. Recent experimental data implicate a casual role of prolactin in the development of PPCM. Prolactin secretion can be reduced with bromocriptine which had beneficial effects in a small study. We present a Japanese woman with acute PPCM treated with bromocriptine as a therapeutic option. Following treatment, the serum prolactin levels dropped swiftly. Concurrently, LV function improved, and heart failure symptoms decreased, accompanied by a decrease in the BNP level.

Topics: Asian People; Bromocriptine; Cardiomyopathies; Dopamine Agonists; Female; Humans; Natriuretic Peptide, Brain; Pleural Effusion; Pregnancy; Pregnancy Complications, Cardiovascular; Pulmonary Edema; Radiography, Thoracic; Time Factors; Ultrasonography

The extracellular matrix (ECM) is a major determinant of the structural integrity and functional properties of the myocardium in common pathological conditions, and changes in vasculature contribute to cardiac dysfunction. Collagen (Col) XV is preferentially expressed in the ECM of cardiac muscle and microvessels.. We aimed to characterize the ECM, cardiovascular function and responses to elevated cardiovascular load in mice lacking Col XV (Col15a1(-/-)) to define its functional role in the vasculature and in age- and hypertension-associated myocardial remodeling.. Cardiac structure and vasculature were analyzed by light and electron microscopy. Cardiac function, intraarterial blood pressure, microhemodynamics, and gene expression profiles were studied using echocardiography, telemetry, intravital microscopy, and PCR, respectively. Experimental hypertension was induced with angiotensin II or with a nitric oxide synthesis inhibitor. Under basal conditions, lack of Col XV resulted in increased permeability and impaired microvascular hemodynamics, distinct early-onset and age-dependent defects in heart structure and function, a poorly organized fibrillar collagen matrix with marked interstitial deposition of nonfibrillar protein aggregates, increased tissue stiffness, and irregularly organized cardiomyocytes. In response to experimental hypertension, Col15a1 gene expression was increased in the left ventricle of wild-type mice, and mRNA expression of natriuretic peptides (ANP and BNP) and ECM modeling were abnormal in Col15a1(-/-) mice.. Col XV is necessary for ECM organization in the heart, and for the structure and functions of microvessels. Col XV deficiency leads to a complex cardiac phenotype and predisposes the subject to pathological responses under cardiac stress.

Topics: Age Factors; Aging; Angiotensin II; Animals; Atrial Natriuretic Factor; Cardiomyopathies; Collagen; Coronary Circulation; Disease Models, Animal; Echocardiography; Elasticity; Enzyme Inhibitors; Extracellular Matrix; Female; Gene Expression Profiling; Gene Expression Regulation; Genotype; Heart Ventricles; Hemodynamics; Hypertension; Male; Mice; Mice, 129 Strain; Mice, Inbred C57BL; Mice, Knockout; Microcirculation; Microscopy, Electron; Microscopy, Video; Myocardium; Natriuretic Peptide, Brain; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Phenotype; Polymerase Chain Reaction; RNA, Messenger; Telemetry; Ventricular Remodeling

The M-band represents a transverse structure in the center of the sarcomeric A-band and provides an anchor for the myosin-containing thick filaments. In contrast to other sarcomeric structures, eg, the Z-disc, only few M-band-specific proteins have been identified to date, and its exact molecular composition remains unclear.. Using a bioinformatic approach to identify novel heart- and muscle-specific genes, we found a leucine rich protein, myomasp (Myosin-interacting, M-band-associated stress-responsive protein)/LRRC39. RT-PCR and Northern and Western blot analyses confirmed a cardiac-enriched expression pattern, and immunolocalization of myomasp revealed a strong and specific signal at the sarcomeric M-band. Yeast 2-hybrid screens, as well as coimmunoprecipitation experiments, identified the C terminus of myosin heavy chain (MYH)7 as an interaction partner for myomasp. Knockdown of myomasp in neonatal rat ventricular myocytes (NRVCMs) led to a significant upregulation of the stretch-sensitive genes GDF-15 and BNP. Conversely, the expression of MYH7 and the M-band proteins myomesin-1 and -2 was found to be markedly reduced. Mechanistically, knockdown of myomasp in NRVCM led to a dose-dependent suppression of serum response factor-dependent gene expression, consistent with earlier observations linking the M-band to serum response factor-mediated signaling. Finally, downregulation of myomasp/LRRC39 in spontaneously beating engineered heart tissue constructs resulted in significantly lower force generation and reduced fractional shortening. Likewise, knockdown of the myomasp/LRRC39 ortholog in zebrafish resulted in severely impaired heart function and cardiomyopathy in vivo.. These findings reveal myomasp as a previously unrecognized component of an M-band-associated signaling pathway that regulates cardiomyocyte gene expression in response to biomechanical stress.

Topics: Amino Acid Sequence; Animals; Animals, Newborn; Blotting, Northern; Blotting, Western; Cardiac Myosins; Cardiomyopathies; Carrier Proteins; Cells, Cultured; Cloning, Molecular; Connectin; Embryo, Nonmammalian; Gene Expression Profiling; Gene Expression Regulation; Growth Differentiation Factor 15; Humans; Immunohistochemistry; Immunoprecipitation; Leucine-Rich Repeat Proteins; Male; Mechanotransduction, Cellular; Mice; Mice, Inbred C57BL; Molecular Sequence Data; Muscle Proteins; Muscle, Skeletal; Myocardial Contraction; Myocytes, Cardiac; Myosin Heavy Chains; Natriuretic Peptide, Brain; Oligonucleotide Array Sequence Analysis; Protein Interaction Domains and Motifs; Protein Interaction Mapping; Proteins; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reverse Transcriptase Polymerase Chain Reaction; RNA Interference; Sarcomeres; Serum Response Factor; Stress, Mechanical; Transfection; Two-Hybrid System Techniques; Zebrafish

Cardiac involvement and pulmonary hypertension (PH) are life-threatening complications in sarcoidosis.. This study aimed to investigate the utility of plasma NT-proBNP in the assessment of these conditions in sarcoidosis patients.. A prospective, observational study was performed on 150 consecutive Japanese sarcoidosis patients. Doppler echocardiography was performed in all subjects, and those who were successfully evaluated for PH status were included in the analysis. Cardiac sarcoidosis was diagnosed based on Japanese guidelines, and PH was defined as estimated systolic pulmonary artery pressure (sPAP) > or = 35 mmHg. The diagnostic accuracy of NT-proBNP according to the presence of cardiac sarcoidosis and PH was assessed based on receiver-operator characteristic (ROC) curves.. 130 subjects were successfully evaluated for PH status. Of these, 29 met the diagnostic criteria of cardiac sarcoidosis, and 21 were diagnosed with PH. Plasma NT-proBNP levels were significantly higher in patients with cardiac sarcoidosis (p < 0.0001). Stepwise regression analysis showed that presence of cardiac sarcoidosis, decreased ejection fraction and increased sPAP were all independently associated with higher plasma NT-proBNP levels. Plasma NT-proBNP showed good accuracy in identifying patients with cardiac sarcoidosis (area under the ROC curve; AURC = 0.913). However, even when patients with cardiac sarcoidosis were excluded, plasma NT-proBNP levels could not be used reliably to identify patients with PH (AURC = 0.681).. In patients with sarcoidosis, plasma NT-proBNP levels are a useful biomarker to identify cardiac involvement, but not to identify PH.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Blood Pressure; Cardiomyopathies; Chi-Square Distribution; Echocardiography, Doppler; Female; Humans; Hypertension, Pulmonary; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Pulmonary Artery; Regression Analysis; ROC Curve; Sarcoidosis; Stroke Volume; Up-Regulation

Brain natriuretic peptide is a cardiac neurohormone secreted from ventricles in response to end diastolic pressure and increased volume. It has diuretic, natriuretic and vasodilator effects. In cirrhosis, a hyperdynamic circulation occurs because of hemodynamic and hemostatic alterations. The increase in brain natriuretic peptide concentration shows parallelism with the stage of cirrhosis. The aim of this study is to investigate the relation of increased brain natriuretic peptide level with the pathophysiologic components of cirrhosis and treatment.. Ninety-five cirrhotic patients in different stages (Child-A: 33; Child-B: 25; Child-C:37) and age and sex matched 86 healthy individuals were recruited for the study. Brain natriuretic peptide concentration was measured with brain natriuretic peptide-Triage test device using fluoresan immune assay method.. Brain natriuretic peptide levels of patients with hepatic cirrhosis were significantly higher compared to control group (288.5±329.2/60.2±29.5/p=0.000, respectively). Serum brain natriuretic peptide levels were positively correlated with Child score (Child A-B-C; 201.2±266/258.7±233.6/386.5±407.7, respectively). A negative correlation was observed between brain natriuretic peptide and albumin levels (p=0.002). Brain natriuretic peptide concentration was significantly correlated with the grade of esophagus varices, and presence of ascites and collateral circulation (p=0.006; p=0.001; p=0.002; respectively). Patients receiving with beta-blocker and diuretic treatments had significantly higher brain natriuretic peptide levels.. High brain natriuretic peptide levels in patients with cirrhosis may be due to hepatocellular insufficiency or portal hypertension, but a cardiomyopathy developing insiduously should not be regarded.

Topics: Adrenergic beta-Antagonists; Adult; Biomarkers; Cardiomyopathies; Diuretics; Female; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Failure; Male; Middle Aged; Natriuretic Peptide, Brain; Serum Albumin; Severity of Illness Index

The aetiology of peripartum cardiomyopathy (PPCM) is still largely unknown. Recent evidence suggests that the breakdown products from prolactin can induce cardiomyopathy. Prolactin secretion can be reduced with bromocriptine which had beneficial effects in a small study. We present a case of a patient with PPCM who received cabergoline, a strong and long lasting antagonist of prolactin secretion. Following treatment, her prolactin levels dropped swiftly. N-terminal pro-BNP levels, which had remained high up to that point, dropped within 1 day (7006 to 4408 pg/mL). Echocardiographic left ventricular ejection fraction recovered from 26% on day 4 postpartum to 32% and later 47% on days 2 and 5 after cabergoline treatment. To our knowledge, this is the first description of a case of PPCM in which cabergoline was administered.

Topics: Adult; Cabergoline; Cardiomyopathies; Echocardiography; Ergolines; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Prolactin; Puerperal Disorders; Ventricular Dysfunction, Left

The aim of our study was to determine concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with cirrhosis, thereby describing the hemodynamic and cardiac profiles to verify the existence of cirrhotic cardiomyopathy.. Clinical data, NT-proBNP levels, echocardiography, and right heart hemodynamic measurements were performed on all patients undergoing liver transplantation for cirrhosis.. Our patients showed a hyperdynamic circulation with elevated left-sided pressures despite high cardiac outputs. This observation suggested abnormalities in left ventricular diastolic compliance. We verified these results, because our cohort showed a significant left ventricular mass index and, consequently, diastolic dysfunction. Mean NT-proBNP levels were high. The great expansion of central volume may explain these results and the later development of left ventricular hypertrophy.. We concluded that elevated concentrations of NT-proBNP indicated the presence of hyperdynamic syndrome and cardiac dysfunction.

Topics: Biomarkers; Blood Pressure; Carcinoma, Hepatocellular; Cardiac Catheterization; Cardiac Output; Cardiomyopathies; Diastole; Heart; Heart Diseases; Heart Rate; Hemodynamics; Hepatitis B; Hepatitis C; Humans; Hypertension; Liver Cirrhosis; Liver Cirrhosis, Alcoholic; Liver Neoplasms; Liver Transplantation; Natriuretic Peptide, Brain; Systole; Vascular Resistance

Serum B-type natriuretic peptide (BNP) is frequently elevated after subarachnoid hemorrhage (SAH), but whether this high BNP level is related to transient elevation of left ventricular filling pressure (LVFP) is unknown. However, in patients with preexistent cardiac pathologies, it is impossible to differentiate between BNP elevation caused by chronic cardiac abnormalities and BNP related to acute neurocardiac injury.. All adult patients with SAH admitted to our intensive care unit were eligible. Patients were excluded for the following reasons: admission >48 hours after aneurysm rupture, pre-existing hypertension, or cardiac disease. Levels of BNP and cardiac troponin Ic were measured daily for 7 days. Echocardiography was performed by a blinded cardiologist on days 1, 2, and 7. Doppler signals from the mitral inflow, tissue Doppler, and the color M-mode-derived flow propagation velocity (FPV) were obtained to assess echo-estimated LVFP.. During a 3-year period, sixty-six consecutive patients with SAH were admitted. Thirty one patients were studied. The BNP level was >100 ng/L in 25 patients (80%) during the first 3 days, with a peak on day 2 (median, 126 ng/L) followed by a gradual decrease (median variation days 1 to 7, 70%). All patients had an ejection fraction >50%. Early transmitral velocity/tissue Doppler mitral annular early diastolic velocity was low: 5.4 (+/- 1.5) on day 1, 5.8 (+/- 1.2) on day 2, and 5.1 (+/- 0.9) on day 7. Early transmitral velocity/FPV was also low: 1.27 (+/- 0.4), 1.25 (+/- 0.3), and 1.1 (+/- 0.2) on days 1, 2, and 7, respectively. Cardiac troponin Ic levels ranged from 0 to 3.67 microg/L and were correlated with BNP (r = 0.63, P < 0.01).. BNP rises gradually over two days and return to normal within a week after SAH. Its release is associated with myocardial necrosis, but is unrelated to elevated LVFP assessed by echocardiography.

Topics: Acute Disease; Adult; Cardiomyopathies; Echocardiography, Doppler; Female; Hemodynamics; Humans; Male; Natriuretic Peptide, Brain; Necrosis; Prospective Studies; Subarachnoid Hemorrhage; Troponin I; Ventricular Dysfunction, Left

Diabetic cardiomyopathy is an important contributor to diastolic and systolic heart failure. We examined the nature and mechanism of the cardiomyopathy in Akita (Ins2(WT/C96Y)) mice, a model of genetic nonobese type 1 diabetes that recapitulates human type 1 diabetes. Cardiac function was evaluated in male Ins2WT/C96Y and their littermate control (Ins2WT/WT) mice using echocardiography and tissue Doppler imaging, in vivo hemodynamic measurements, as well as ex vivo working heart preparation. At 3 and 6 mo of age, Ins2WT/C96Y mice exhibited preserved cardiac systolic function compared with Ins2WT/WT mice, as evaluated by ejection fraction, fractional shortening, left ventricular (LV) end-systolic pressure and maximum rate of increase in LV pressure in vivo, cardiac work, cardiac power, and rate-pressure product ex vivo. Despite the unaltered systolic function, Ins2WT/C96Y mice exhibited significant and progressive diastolic dysfunction at 3 and 6 mo of age compared with Ins2WT/WT mice as assessed by tissue and pulse Doppler imaging (E-wave velocity, isovolumetric relaxation time) and by in vivo hemodynamic measurements (LV end-diastolic pressure, time constant of LV relaxation, and maximum rate of decrease in LV pressure). We found no evidence of myocardial hypertrophy or fibrosis in the Ins2WT/C96Y myocardium. Consistent with the lack of fibrosis, expression of procollagen-alpha type I, procollagen-alpha type III, and fibronectin were not increased in these hearts. Ins2WT/C96Y hearts showed significantly reduced sarcoplasmic reticulum Ca2+-ATPase 2a (cardiac sarcoplasmic reticulum Ca2+ pump) levels, elevated beta-myosin heavy chain isoform, increased long-chain fatty acids, and triacylglycerol with evidence of lipotoxicity, as indicated by a significant rise in ceramide, diacylglycerol, and lipid deposits in the myocardium. Consistent with metabolic perturbation, and a switch to fatty acid oxidation from glucose oxidation in Ins2WT/C96Y hearts, expression of mitochondrial long-chain acyl-CoA dehydrogenase and pyruvate dehydrogenase kinase isoform 4 were increased. Insulin treatment reversed the diastolic dysfunction, the elevated B-type natriuretic peptide and beta-myosin heavy chain, and the reduced sarcoplasmic reticulum Ca2+-ATPase 2a levels with abolition of cardiac lipotoxicity. We conclude that early type 1 diabetic cardiomyopathy is characterized by diastolic dysfunction associated with lipotoxic cardiomyopathy with preserved systolic function in t

Topics: Acyl-CoA Dehydrogenase, Long-Chain; Age Factors; Animals; Blood Glucose; Cardiomyopathies; Ceramides; Diabetes Mellitus, Type 1; Diastole; Diglycerides; Disease Models, Animal; Disease Progression; Echocardiography, Doppler, Pulsed; Fatty Acids; Hypoglycemic Agents; Insulin; Lipid Metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Mitochondria, Heart; Myocardial Contraction; Myocardium; Myosin Heavy Chains; Natriuretic Peptide, Brain; Protein Serine-Threonine Kinases; Pyruvate Dehydrogenase Acetyl-Transferring Kinase; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Stroke Volume; Systole; Triglycerides; Ventricular Dysfunction, Left; Ventricular Pressure

The prognostic value of NT-proBNP has been recognized in patients with amyloidosis complicated by cardiac involvement. We aimed to use contrast enhanced cardiac magnetic resonance imaging (CMR) to identify functional and structural alterations related to levels of NT-proBNP better to understand the mechanisms of its release in cardiac amyloidosis.. CMR was performed on a 1.5-T scanner in 34 patients with biopsy proven amyloid light chain (AL; n = 27) or hereditary transthyretin related (TTR; n = 7) amyloidosis. NT-proBNP was higher in patients with (n = 25) compared to patients without cardiac involvement (n = 9) (2931 (IQR: 972-8629; min-max: 25-27,277) pg/ml vs. 177 (IQR: 71-1431; min-max: 22-7935) pg/ml, p = 0.008). ROC analysis identified a NT-proBNP of <2426.5 pg/ml as optimal discriminator for event free survival (682 +/- 65 days). NT-proBNP did not correlate with LV- ejection fraction, end-diastolic and end-systolic volumes or stroke volume. There was a moderate correlation between NT-proBNP and LV-mass (R = 0.52, p = 0.003) and extent of late gadolinium enhancement (LGE; R = 0.41, p = 0.04).. This study confirms the prognostic value of NT-proBNP in patients with AL and TTR amyloidosis and provides the novel finding that NT-proBNP correlates with surrogates of myocardial amyloid burden such as LV-mass and LGE, supporting the concept of NT-proBNP as a biomarker reflecting the severity of cardiac amyloid infiltration.

Topics: Amyloid; Amyloidosis; Cardiomyopathies; Contrast Media; Female; Gadolinium; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

Myocardial ischemia and infarction after surgery remain leading causes of morbidity and mortality in patients undergoing major vascular surgery. B-type natriuretic peptide has been shown to predict early postoperative cardiac events in patients undergoing major noncardiac surgery. We aimed to determine if N-terminal pro B-type natriuretic peptide (NT-pro-BNP), with its longer half-life and greater plasma stability, can predict postoperative myocardial injury in vascular patients.. Recruited were 136 patients undergoing elective surgery for subcritical limb ischemia or abdominal aortic aneurysm (AAA) repair. Plasma NT-pro-BNP was measured preoperatively, and troponin-I was measured immediately after surgery and on postoperative days 1, 2, 3, and 5.. Twenty-eight patients (20%) sustained postoperative myocardial injury (troponin-I rise of >0.1 ng/mL). The median NT-pro-BNP level of those with myocardial injury was significantly higher than those who did not (380 pg/mL [interquartile range (IQR), 223-967] vs 209 pg/mL [109-363]; P = .003). NT-pro-BNP predicted this outcome with an area under the receiver operating characteristic (ROC) curve of 68% (95% confidence interval [CI] 0.56%-0.78%). In a multivariate analysis, a NT-pro-BNP value of >/=308 pg/mL (the optimal ROC curve-derived cutoff) was associated with an increased incidence of myocardial injury (odds ratio, 3.4; 95% CI, 1.41-9.09, P =.01).. Elevated preoperative plasma NT-pro-BNP levels independently predict postoperative myocardial injury, which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome.

Topics: Adult; Aged; Aged, 80 and over; Cardiomyopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Preoperative Care; Prospective Studies; Troponin I; Vascular Surgical Procedures

NT pro-BNP is a marker of systolic and diastolic dysfunction.. To determine NT pro-BNP levels in patients with chagasic, hypertrophic, and restrictive heart diseases, as well as with pericardial diseases, and their relation to echocardiographic measurements of systolic and diastolic dysfunction.. A total of 145 patients were divided into the following groups: 1) Chagas' heart disease (CHD)--14 patients; 2) hypertrophic cardiomyopathy (HCM)--71 patients; 3) endomyocardial fibrosis (EMF)--26 patients; 4) pericardial effusion (PE)--18 patients; and 5) constrictive pericarditis (CP)--16 patients. The control group was comprised of 40 individuals with no heart disease. The degree of myocardial impairment and pericardial effusion were assessed by two-dimensional echocardiography and the degree of restriction by pulsed Doppler transmitral flow. The diagnosis of CP was confirmed through magnetic resonance imaging. NT pro-BNP levels were determined through electrochemiluminescence immunoassay.. NT pro-BNP was increased (p < 0.001) in CHD (median = 513.8 pg/ml), HCM (median = 848 pg/ml), EMF (median = 633 pg/ml), CP (median = 568 pg/ml), and PE (median = 124 pg/ml), when compared with the control group (median = 28 pg/ml). No statistically significant differences were found between CP and EMF (p = 0.14). In the hypertrophic group, NT pro-BNP was correlated with left atrial size (r = 0.40; p < 0.001) and with E/Ea ratio (p < 0.01). In the restrictive group, there was a trend of correlation with E-wave peak velocity (r = 0.439; p = 0.06).. NT pro-BNP is increased in the different cardiomyopathies and pericardial diseases and is correlated with the degree of systolic and diastolic dysfunction.

Topics: Adult; Biomarkers; Cardiomyopathies; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; Case-Control Studies; Chagas Cardiomyopathy; Diastole; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Pericardial Effusion; Pericarditis, Constrictive; Pericardium; Prospective Studies; Systole; Ultrasonography; Ventricular Dysfunction

The objective of our study was to use MRI to analyze the topographic localization of myocardial lesions and their relationship to plasma brain natriuretic peptide (BNP) levels and several cardiac function parameters in patients with cardiac sarcoidosis.. Delayed contrast-enhanced MRI was performed in 40 patients with sarcoidosis (11 cardiac, 29 extracardiac cases). Using a 29-segment model of the left ventricle (LV), the extent of myocardial hyperenhancement was visually scored (0 = no hyperenhancement, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, 4 = 76-100% hyperenhancement) and was compared with plasma BNP level and several parameters of cardiac function.. Ten of the 11 patients with cardiac sarcoidosis showed myocardial hyperenhancement, whereas none of the 29 patients without cardiac sarcoidosis did. In patients with cardiac sarcoidosis, hyperenhancement was significantly more extensive in basal short axis slices than in apical short axis slices (p < 0.0005). Myocardial hyperenhancement was significantly more frequent in subepicardial layers than in subendocardial layers. The global extent of myocardial hyperenhancement was significantly correlated with plasma BNP levels and the LV end-diastolic volume index and was negatively correlated with the LV ejection fraction.. In patients with cardiac sarcoidosis, myocardial lesions detected on delayed contrast-enhanced MRI were predominantly localized in the basal and subepicardial myocardium. The extent of myocardial lesions may be related to LV dysfunction and plasma BNP level in patients with cardiac sarcoidosis.

Topics: Cardiomyopathies; Female; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Reproducibility of Results; Sarcoidosis; Sensitivity and Specificity; Ventricular Dysfunction, Left

To evaluate the mechanisms and the impact of the angiotensin-converting enzyme inhibitor perindopril (P) in a model of doxorubicin (D)-induced cardiotoxicity, male Wistar rats received D (1 mg/kg/d, IP for 10 days), P (2 mg/kg/d by gavage from day 1 to day 18), D (for 10 days) + P (for 18 days) or saline. D decreased systolic blood pressure and body and heart weights. Left ventricular diastolic diameter was increased by D (P < 0.01), but it was not attenuated by P. D decreased plasma vitamin C (P < 0.05) and increased the ascorbyl radical/vitamin C ratio (P < 0.01). This ratio was attenuated by P. No difference was found among groups in cardiac troponin I, brain natriuretic peptide concentrations, and tissue oxidative stress (OS). Myocardial MCP-1 expression was higher in the D group. Cardiac kinin receptor (B1R and B2R) expression was not affected by D, yet binding sites for B2R and B1R were increased in D+P and P groups, respectively (P < 0.05). In conclusion, D induced cardiac functional alterations, inflammation and plasma OS whereas tissue OS, and cardiac kinin receptors expression were not modified. P did not improve cardiac performance, but it modulated kinin receptor expression and enhanced antioxidant defense.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antibiotics, Antineoplastic; Ascorbic Acid; Binding Sites; Blood Pressure; Cardiomyopathies; Chemokine CCL2; Doxorubicin; Gene Expression Regulation; Male; Natriuretic Peptide, Brain; Oxidative Stress; Perindopril; Rats; Rats, Wistar; Receptor, Bradykinin B1; Receptor, Bradykinin B2; Troponin I

Cardiac involvement is common in amyloidosis and associated with a variably adverse outcome. We have previously shown that cardiovascular magnetic resonance (CMR) can assess deposition of amyloid protein in the myocardial interstitium. In this study we assessed the prognostic value of late gadolinium enhancement (LGE) and gadolinium kinetics in cardiac amyloidosis in a prospective longitudinal study.. The pre-defined study end point was all-cause mortality. We prospectively followed a cohort of 29 patients with proven cardiac amyloidosis. All patients underwent biopsy, 2D-echocardiography and Doppler studies, 123I-SAP scintigraphy, serum NT pro BNP assay, and CMR with a T1 mapping method and late gadolinium enhancement (LGE).. Patients with were followed for a median of 623 days (IQ range 221, 1436), during which 17 (58%) patients died. The presence of myocardial LGE by itself was not a significant predictor of mortality. However, death was predicted by gadolinium kinetics, with the 2 minute post-gadolinium intramyocardial T1 difference between subepicardium and subendocardium predicting mortality with 85% accuracy at a threshold value of 23 ms (the lower the difference the worse the prognosis). Intramyocardial T1 gradient was a better predictor of survival than FLC response to chemotherapy (Kaplan Meier analysis P = 0.049) or diastolic function (Kaplan-Meier analysis P = 0.205).. In cardiac amyloidosis, CMR provides unique information relating to risk of mortality based on gadolinium kinetics which reflects the severity of the cardiac amyloid burden.

Topics: Aged; Amyloidosis; Biomarkers; Biopsy; Cardiomyopathies; Contrast Media; Echocardiography, Doppler; Female; Gadolinium DTPA; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Assessment; Severity of Illness Index; Time Factors

The progression of cardiac amyloidosis is a prognostic factor after liver transplantation (LT) in familial amyloid polyneuropathy (FAP). The aim of this study was to assess myocardial changes in FAP amyloidgenic transthyretin (ATTR) Val30Met after LT.. Twelve Japanese FAP ATTR Val30Met patients who underwent LT and were followed for more than 2 years, were examined with serial echocardiography after LT. Serum BNP levels were measured in 9 patients.. A significant increase in mean left atrial diameter and interventricular septal thickness was observed after LT. The increase in left atrial diameter was correlated with the presence of granular sparkling echo (GSE) at preoperative examination. Serum brain natriuretic peptide (BNP) levels in patients with left atrial diameter dilation (152.0+/-157.6 pg/mL) were higher than in those without left atrial diameter dilation (32.0+/-30.0 pg/mL).. LAD and IVS were significantly increased after LT compared with preoperative examinations in Japanese FAP ATTR Val30Met patients. BNP is an important biochemical indicator of myocardiac dysfunction in FAP patients. GSE is a useful echocardiographic marker to predict cardiac amyloidosis after LT.

Topics: Adult; Aged; Amyloid Neuropathies, Familial; Amyloidosis; Biomarkers; Cardiomyopathies; Female; Humans; Liver Transplantation; Male; Middle Aged; Natriuretic Peptide, Brain; Ultrasonography

Cardiac amyloidosis is characterized by amyloid infiltration resulting in extracellular matrix disruption. Amyloid cardiomyopathy due to immunoglobulin light chain protein (AL-CMP) deposition has an accelerated clinical course and a worse prognosis compared with non-light chain cardiac amyloidoses (ie, forms associated with wild-type or mutated transthyretin [TTR]). We therefore tested the hypothesis that determinants of proteolytic activity of the extracellular matrix, the matrix metalloproteinases (MMPs), and their tissue inhibitors (TIMPs) would have distinct patterns and contribute to the pathogenesis of AL-CMP versus TTR-related amyloidosis.. We studied 40 patients with systemic amyloidosis: 10 AL-CMP patients, 20 patients with TTR-associated forms of cardiac amyloidosis, ie, senile systemic amyloidosis (involving wild-type TTR) or mutant TTR, and 10 patients with AL amyloidosis without cardiac involvement. Serum MMP-2 and -9, TIMP-1, -2, and -4, brain natriuretic peptide values, and echocardiography were determined. AL-CMP and TTR-related amyloidosis groups had similar degrees of increased left ventricular wall thickness. However, brain natriuretic peptide, MMP-9, and TIMP-1 levels were distinctly elevated accompanied by marked diastolic dysfunction in the AL-CMP group versus no or minimal increases in the TTR-related amyloidosis group. Brain natriuretic peptide, MMPs, and TIMPs were not correlated with the degree of left ventricular wall thickness but were correlated to each other and to measures of diastolic dysfunction. Immunostaining of human endomyocardial biopsies showed diffuse expression of MMP-9 and TIMP-1 in AL-CMP and limited expression in TTR-related amyloidosis hearts.. Despite comparable left ventricular wall thickness with TTR-related cardiac amyloidosis, AL-CMP patients have higher brain natriuretic peptide, MMPs, and TIMPs, which correlated with diastolic dysfunction. These findings suggest a relationship between light chains and extracellular matrix proteolytic activation that may play an important role in the functional and clinical manifestations of AL-CMP, distinct from the other non-light chain cardiac amyloidoses.

Topics: Aged; Amyloid; Amyloidosis; Biomarkers; Cardiomyopathies; Echocardiography; Extracellular Matrix; Female; Heart Ventricles; Humans; Immunoglobulin Light Chains; Kidney Diseases; Male; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Mutation; Myocardium; Natriuretic Peptide, Brain; Peptide Hydrolases; Prealbumin; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinases; Ventricular Function, Left; Ventricular Remodeling

Cardiomyopathy is a well known complication in familial amyloidotic polyneuropathy (FAP). Troponin T and B-natriuretic peptide (BNP) have been shown to be excellent markers for heart complications in AL-amyloidosis. The aim of the study was to investigate troponin T, troponin I and BNP as markers for myocardial damage and failure in FAP.. Retrospective investigation of patients with FAP.. Tertiary referral centre.. Twenty-nine patients who had been submitted for evaluation of FAP.. Two-dimensional M-mode and Doppler echocardiography and strain echocardiographic examination. Measurement of Troponin T, troponin I and BNP.. Troponin T was detectable in only three patients who all had abnormal interventricular septal (IVS) thickness. Troponin I was abnormal in six patients (21%), of which only two had an increased IVS thickness. The heart function was generally well preserved in the patients in spite of hypertrophy of the IVS in 14 patients. BNP was elevated in 22 patients (76%), and it correlated significantly with IVS thickness and basal septal strain.. Transthyretin amyloid seems to be less harmful to myocytes than that of AL amyloid as evaluated by serum troponin T and I as well as by echocardiography. BNP appears to be a sensitive marker for cardiomyopathy in FAP, and could prove valuable for follow-up purposes as has been shown for AL-amyloidosis patients.

Topics: Adult; Aged; Amyloid; Amyloid Neuropathies, Familial; Biomarkers; Cardiomyopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prealbumin; Retrospective Studies; Troponin I; Troponin T; Ultrasonography

Anthracycline therapy is limited by cardiotoxicity. Currently no diagnostic parameter is available allowing ubiquitous and reliable detection of preclinical anthracycline cardiomyopathy and prediction of prognosis.. In 100 consecutive patients receiving anthracycline-based chemotherapy serial measurements of left ventricular systolic and diastolic function, Tei index (a Doppler echocardiographic parameter of global ventricular function), cardiac troponin T (cTnT) and NT-probrain natriuretic peptides (BNP) at baseline and during 1-year follow-up were performed.. Mean ejection fraction (LVEF) significantly decreased immediately after completion of anthracycline therapy (mean dose 226.1 +/- 8.3 mg/m(2)) und further declined during follow-up (65.9 +/- 0.6% Vs. 61.6 +/- 0.7%; P < 0.001), while mean E/A ratio decreased after 6 months (P = 0.05). No patient presented with cardiac symptoms. The Tei index increased after therapy in the majority of patients (78.8%) compared with pre-therapy values indicating myocardial alteration in more patients than previously recognized. cTnT levels did not exceed the upper limit of the normal range in any patient. Seven patients had low-level elevations of cTnT. Only one of these patients developed a concomitant decrease in LVEF. Mean N-terminal-pro-BNP (NT-proBNP) levels did not significantly change after anthracycline administration. However, in 13 patients (15.3%) a marked, transient increase of NT-proBNP was obtained after the first anthracycline cycle without cardiac dysfunction presumably due to altered cardiac loading conditions during chemotherapy.. Low to moderate doses of anthracyclines resulted in subclinical myocardial alteration in more patients than so far noticed. Clinical implications of increased Tei index remain to be determined in long-term. Our results do not support that assessment of cTnT or BNP levels may safely replace serial echocardiographic evaluation of systolic and diastolic function for the monitoring of anthracycline cardiotoxicity.

Topics: Adult; Aged; Anthracyclines; Biomarkers; Cardiomyopathies; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Ventricles; Humans; Immunoassay; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Prognosis; Protein Precursors; Time Factors; Troponin T; Ventricular Function, Left

Patients with nonischemic cardiomyopathy (DCM) are at high risk for sudden cardiac death (SCD). However, the predictive value of prophylactic implantation of implantable cardioverter defibrillators (ICD) in this patient cohort is yet unclear.. Whether NT pro BNP levels and/or reproducible non sustained ventricular tachycardias (NSVTs) are predictive for SCD was prospectively tested in 30 patients with DCM and LVEF

Topics: Arrhythmias, Cardiac; Biomarkers; Cardiomyopathies; Disease Progression; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Prospective Studies; Risk Factors; ROC Curve

The aim of the study was to determine the incidence of myocardial dysfunction in an HIV-infected population receiving state-of-the-art treatment.. Between April 2001 and July 2002, 91 HIV-infected patients had a radionuclide ventriculography performed with determination of right ventricular ejection fraction (RVEF) and left ventricular ejection fraction (LVEF), as well as measurement of brain natriuretic peptide (BNP). Between July 2005 and January 2007, 63 patients (69%) agreed to participate in a follow-up study with a mean follow-up of 4.5 years.. All patients had normal LVEF at both examinations. A minimal increase in mean LVEF of 0.02 was observed at follow-up (P=0.01). At the initial visit, four patients [6%; 95% confidence interval (CI) 2-15%] had a reduced RVEF, and at follow-up two patients (3%; 95% CI 0-11%) had slightly reduced RVEF. No significant change in mean RVEF was found. No patients had increased BNP and no change in mean plasma BNP was found.. HIV-related cardiomyopathy appears not to constitute a problem in closely monitored, well-treated HIV-infected patients. Compared with pre-highly active antiretroviral therapy (HAART) studies, it seems that the improvement in immunocompetency and viral load has removed the problem of HIV-related cardiomyopathy. Although HAART has been suggested as a possible new cause of cardiomyopathy, we did not find any evidence of this.

Topics: Adult; Antiretroviral Therapy, Highly Active; Cardiomyopathies; Female; Follow-Up Studies; HIV Infections; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Radionuclide Ventriculography; Radiopharmaceuticals; Stroke Volume; Technetium Tc 99m Aggregated Albumin; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Viral Load

Tachycardia-induced cardiomyopathy is characterized by ventricular systolic dysfunction and congestive heart failure resulting from persistent or highly frequent tachyarrhythmias with uncontrolled heart rate. While reversible and often considered benign, few studies have examined the outcome of the disorder. The clinical characteristics, treatment, and long-term outcomes of 12 consecutive patients with tachycardia-induced cardiomyopathy (9 men, age, 51.9 +/- 17.6 years) were studied. The mean period between the occurrence of tachyarrhythmias and the development of congestive heart failure was 26.0 +/- 34.3 days. The mean heart rate on admission was 156.3 +/- 28.7 beats/min. All patients had severe heart failure with a NYHA functional class of 2.3 +/- 0.5, left ventricular ejection fraction of 0.32 +/- 0.10, and brain natriuretic peptide level of 505.7 +/- 449.1 pg/mL. In all patients, cardiac dysfunction recovered after 53.5 +/- 61.3 days. During the follow-up of 53 +/- 24 months, 2 patients had a recurrence of heart failure with uncontrolled tachyarrhythmia and 1 patient died suddenly. In tachycardia-induced cardiomyopathy, recurrent heart failure with uncontrollable tachyarrhythmia and sudden death were observed after recovery from cardiac dysfunction. A substrate for heart failure and/or life-threatening arrhythmia might persist, and careful, long-term follow-up seems required.

Topics: Adult; Aged; Cardiomyopathies; Death, Sudden, Cardiac; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Recurrence; Stroke Volume; Tachycardia; Treatment Outcome; Ventricular Dysfunction

Diabetic cardiomyopathy, structurally characterized by cardiomyocyte hypertrophy and increased extracellular matrix (ECM) protein deposition, eventually leads to heart failure. We investigated the role of transcriptional coactivator p300 and its interaction with myocyte enhancer factor 2 (MEF2) in diabetes-induced cardiomyocyte hypertrophy. Neonatal rat cardiomyocytes were exposed to variable levels of glucose. Cardiomyocytes were analyzed with respect to their size. mRNA expression of p300, MEF2A, MEF2C, atrial natriuretic polypeptide (ANP), brain natriuretic polypeptide (BNP), angiotensinogen (ANG), cAMP-responsive element binding protein-binding protein (CBP), and protein analysis of MEF2 were done with or without p300 blockade. We investigated the hearts of STZ-induced diabetic rats and compared them with age- and sex-matched controls after 1 and 4 mo of followup with or without treatment with p300 blocker curcumin. The results were that cardiomyocytes, exposed to 25 mM glucose for 48 h, showed cellular hypertrophy and augmented mRNA expression of ANP, BNP, and ANG, molecular markers of cardiac hypertrophy. Glucose caused a duration-dependent increase of mRNA and protein expression in MEF2A and MEF2C and transcriptional coactivator p300. Curcumin, a p300 blocker, and p300 siRNA prevented these abnormalities. Similarly, ANP, BNP, and ANG mRNA expression was significantly higher in the hearts of diabetic rats compared with the controls, in association with increased p300, MEF2A, and MEF2C expression. Treatment with p300 blocker curcumin prevented diabetes-induced upregulation of these transcripts. We concluded that data from these studies demonstrate a novel glucose-induced epigenetic mechanism regulating gene expression and cardiomyocyte hypertrophy in diabetes.

Topics: Angiotensinogen; Animals; Animals, Newborn; Atrial Natriuretic Factor; Blotting, Western; Cardiomyopathies; Diabetes Mellitus, Experimental; Dose-Response Relationship, Drug; Female; Gene Expression Regulation; Glucose; Male; MEF2 Transcription Factors; Myocytes, Cardiac; Myogenic Regulatory Factors; Natriuretic Peptide, Brain; p300-CBP Transcription Factors; Rats; Rats, Sprague-Dawley; RNA, Messenger; Transcription, Genetic

Hypertension is associated with high cardiovascular risk. Both hsCRP and NT-proBNP also have been associated with elevated cardiovascular risk, at least in the long term. Much less is known about the short-term changes in these markers, for example, in hypertensive emergencies. In 59 consecutive patients with hypertensive emergencies, hsCRP and NT-proBNP were measured at baseline and at days 3-4 and 7-10 after admission. All patients with hsCRP levels above 10 mg/l during the study were excluded due to possible infections. We found elevated levels of hsCRP at baseline with a significant decline on days 3-4 (day 0: median 2.53 mg/l, days 3-4: median 1.65 mg/l [p<0.01 vs. baseline], days 7-10 median: 2.00 mg/l). Women had higher hsCRP levels than men, and patients with hypertensive cardiomyopathy by echocardiographic criteria had significantly higher hsCRP levels compared with patients without hypertensive cardiomyopathy throughout the study. NT-proBNP levels were clearly elevated at admission (median 158 ng/l) and declined highly significantly thereafter (day 3-4: 61 ng/l, p<0.0001 vs. baseline; day 7-10: 76 ng/l, p<0.0001 vs. baseline). Patients with hypertensive cardiomyopathy had higher NT-proBNP levels compared with those patients without. In hypertensive emergencies, NT-proBNP levels correspond to levels described in acute coronary syndrome and decline significantly under antihypertensive therapy. In addition, we found an acute decline in hsCRP in the short term after hypertensive emergencies. These data may have importance in the clinical setting of hypertensive emergencies and in the interpretation of epidemiological data.

Topics: Acute Coronary Syndrome; Aged; Blood Pressure; Body Mass Index; C-Reactive Protein; Cardiomyopathies; Echocardiography; Emergencies; Female; Humans; Hypertension; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments

We sought to examine whether the plasma brain natriuretic peptide (BNP) levels are elevated in the cardiac sarcoidosis patients even with a preserved ejection fraction. The data from the patients with either pulmonary sarcoidosis without any evidence of cardiac involvement (n = 13) or cardiac sarcoidosis (n = 8) with a preserved ejection fraction (>55%) on echocardiography were analyzed. The median plasma BNP levels were significantly higher in the patients with cardiac sarcoidosis than in those with pulmonary sarcoidosis (101.5 +/- 65.1 vs. 15.6 +/- 10.5 pg/ml, p < 0.001), although there was no significant difference in left ventricular ejection fraction between the two populations. The plasma BNP level is thus considered to be a useful non-invasive biomarker for identifying a possible cardiac involvement in the sarcoidosis patients with a preserved ejection fraction.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Sarcoidosis; Sarcoidosis, Pulmonary; Stroke Volume

Cardiomyopathy due to iron overload represents a frequent life-limiting complication in patients with beta-thalassemia major. We have conducted a study which proved that brain natriuretic peptide plasma levels have high sensitivity and negative predictive value in detecting cardiac hemosiderosis.

Topics: Adult; beta-Thalassemia; Biomarkers; Blood Transfusion; Cardiomyopathies; Cohort Studies; Female; Hemosiderosis; Humans; Iron Overload; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Probability; Prognosis; Sensitivity and Specificity; Severity of Illness Index

To evaluate the use of measuring plasma concentrations of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and cardiac troponin-I (cTnI) to detect dogs with occult dilated cardiomyopathy (DCM).. 118 client-owned dogs.. Dogs were prospectively examined by use of ECG; echocardiography; and evaluation of concentrations of ANP, BNP, and cTnI. Occult DCM was diagnosed by evaluation of echocardiographic left ventricular dimensions and detection of ventricular arrhythmias on ECG. Sensitivity and specificity of assays for measurement of plasma concentrations of ANP, BNP, and cTnI to detect dogs with occult DCM were determined.. Occult DCM was diagnosed in 21 dogs. A concentration of > 6.21 pg/mL for BNP had a sensitivity of 95.2% and specificity of 61.9% for identifying dogs with occult DCM. In contrast, concentrations of ANP and cTnI had relatively low predictive values.. Blood-based screening for occult DCM in dogs can be accomplished by use of a BNP assay. Additional studies should be performed to optimize this method of screening dogs to detect occult DCM.

Topics: Animals; Atrial Natriuretic Factor; Cardiomyopathies; Dog Diseases; Dogs; Echocardiography, Doppler; Electrocardiography; Female; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; ROC Curve; Sensitivity and Specificity; Troponin I

Cardiovascular dysfunction in patients with hemolytic-uremic syndrome (HUS) may be related to secondary issues such as volume overload, hypertension or electrolyte disturbances including hyperkalemia. Additionally, primary myocardial involvement has been increasingly recognized as a potential comorbid feature of HUS. We report a 9-month-old child with HUS who developed clinical signs of poor myocardial function with depressed myocardial function noted by echocardiography. Supportive care including mechanical ventilation and inotropic agents were necessary for approximately 10 days. Follow-up echocardiography revealed return of normal ventricular function. Previous reports of primary cardiac involvement with HUS have included thrombotic microangiopathy of the coronary vasculature resulting in myocardial ischemia, myocardial infarction or depressed myocardial function, myocarditis, congestive heart failure with dilated cardiomyopathy and pericardial effusion with tamponade. Given the potential for morbidity and mortality during the preoperative period in patients with HUS, anesthesiologists involved in the care of such patients should be aware of the potential for myocardial involvement in this disease process. Preoperatively, the routine evaluation of myocardial function may be indicated.

Topics: Anemia; Anti-Bacterial Agents; Cardiomyopathies; Cardiotonic Agents; Dopamine; Electrocardiography; Hemolytic-Uremic Syndrome; Humans; Infant; Intubation, Intratracheal; Male; Meropenem; Milrinone; Natriuretic Agents; Natriuretic Peptide, Brain; Oliguria; Peritoneal Dialysis; Renal Dialysis; Renal Insufficiency; Respiration, Artificial; Thienamycins; Vancomycin

Sustained tachycardia causes left ventricular (LV) systolic dysfunction leading to heart failure (HF), which is widely known as "tachycardia-induced cardiomyopathy (TIC)", but its prevalence and prognosis in Japanese remain unclear.. Of 213 consecutive patients with HF associated with atrial fibrillation (AF) requiring hospitalization (n=213) between January 1999 and December 2004, and 104 (83 males, 67+/-12.6 years) were identified as not having any structural heart disease. Of them 41 (39%) had a normal LV ejection fraction (LVEF) at the initial admission, and the remaining patients fell into 2 groups: those with rapid (<6 months) normalization of the LVEF after AF management (presumed TIC, 30 patients, 29%) and those with persistent LV systolic dysfunction (dilated cardiomyopathy (DCM), 33 patients, 32%). Although the B-type natriuretic peptide value and LVEF did not differ between the 2 groups, the LV size on admission was significantly smaller in the TIC group (LV end-diastolic dimension (LVDd) 57.6+/-7.2, LV end-systolic dimension (LVDs) 49.4+/-8.0) than in the DCM group (LVDd 63.4 +/-8.8, LVDs 55.3+/-9.6, p<0.05). During a follow-up period of 42.1+/-21.2 months, cardiac death and recurrent HF hospitalization were significantly less frequent in the TIC group than in the DCM group.. In AF-associated HF requiring hospitalization, TIC is the presumed cause in approximately one-third of patients without any previously known structural heart disease. That particular group is characterized by a relatively smaller LV and better prognosis under medical treatment.

Topics: Aged; Aged, 80 and over; Asian People; Atrial Fibrillation; Cardiomyopathies; Female; Follow-Up Studies; Heart Failure; Humans; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Tachycardia; Ventricular Dysfunction, Left; Ventricular Function, Left

It has been reported that high intramyocardial peroxisome proliferator-activated receptor alpha (PPARalpha) stimulation or overexpression altered cardiac contractile function in mouse models of cardiac hypertrophy and heart failure. Nevertheless, it has never been demonstrated that clinically relevant doses of drugs stimulating PPARalpha activity such as fenofibrate increase the risk to develop heart failure in humans. To determine if fenofibrate accelerates the development of heart failure in large mammals, we have tested its effects on the progression of left ventricular dysfunction in pacing-induced heart failure in pigs. Fenofibrate treatment blunted reduction in left ventricular ejection fraction, reduced cardiac hypertrophy, and attenuated clinical signs of heart failure. Fenofibrate impeded the increase in atrial natriuretic peptide, brain natriuretic peptide, and endothelin-1 plasma levels. The expression of PPARalpha, fatty acyl-CoA-oxidase, and carnitine palmitoyltransferase-Ibeta was reduced at mRNA levels in the left ventricle from untreated heart failure pigs but maintained near normal values with fenofibrate. Fenofibrate prevented heart failure-induced overexpression of TNFalpha mRNA and enhanced catalase activity in left ventricle compared to placebo. These data suggest that a clinically relevant dose of fenofibrate does not accelerate but slows down heart failure development in the model of pacing-induced heart failure in large mammals.

Topics: Acyl-CoA Oxidase; Animals; Atrial Natriuretic Factor; Biomarkers; Cardiac Output, Low; Cardiomyopathies; Carnitine O-Palmitoyltransferase; Endothelin-1; Female; Fenofibrate; Myocardium; Natriuretic Peptide, Brain; Oxidative Stress; PPAR alpha; RNA, Messenger; Swine; Tachycardia; Thiobarbituric Acid Reactive Substances; Ventricular Dysfunction, Left

Heat shock protein (HSP) 60 is a mitochondrial and cytosolic protein. Previously, we reported that HSP60 doubled in end-stage heart failure, even though levels of the protective HSP72 were unchanged. Furthermore, we observed that acute injury in adult cardiac myocytes resulted in movement of HSP60 to the plasma membrane. We hypothesized that the inflammatory state of heart failure would cause translocation of HSP60 to the plasma membrane and that this would provide a pathway for cardiac injury. Two models were used to test this hypothesis: 1) a rat model of heart failure and 2) human explanted failing hearts. We found that HSP60 localized to the plasma membrane and was also found in the plasma early in heart failure. Plasma membrane HSP60 localized to lipid rafts and was detectable on the cell surface with the use of both flow cytometry and confocal microscopy. Localization of HSP60 to the cell surface correlated with increased apoptosis. In heart failure, HSP60 is in the plasma membrane fraction, on the cell surface, and in the plasma. Membrane HSP60 correlated with increased apoptosis. Release of HSP60 may activate the innate immune system, promoting a proinflammatory state, including an increase in TNF-alpha. Thus abnormal trafficking of HSP60 to the cell surface may be an early trigger for myocyte loss and the progression of heart failure.

Topics: Aged; Animals; Apoptosis; Atrial Natriuretic Factor; Cardiomyopathies; Chaperonin 60; Cytosol; Disease Models, Animal; Disease Progression; Female; Heart Failure; Heart Ventricles; Humans; Male; Membrane Microdomains; Middle Aged; Mitochondria, Heart; Myocardial Contraction; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protein Transport; Rats; Rats, Sprague-Dawley; Time Factors; Tumor Necrosis Factor-alpha; Up-Regulation

Aims The incidence of diabetic cardiomyopathy, independent of arterial hypertension (AH) and coronary heart disease (CHD), remains controversial. The present study aimed to determine the influence of type 1 diabetes mellitus (T1DM) of long duration (>10 years) on myocardial function estimated by echocardiography (ECHO) and serum level of N-terminal pro-B type natriuretic peptide (NT-proBNP) in patients without CHD and AH. We also retrospectively investigated the relationship between the structural changes in the hearts of other deceased T1DM patients, and had their myocardial function echocardiographically assessed before death. Methods and results In 185 patients (96 males) with T1DM (mean duration 22.8 years) and 105 non-diabetic control subjects (57 males), detailed ECHO parameters and NT-proBNP were assessed. No significant differences were found between the respective groups. Histological studies of 17 hearts of deceased T1DM patients were carried out and retrospectively compared with their ECHO performed before death. Histological changes were identified, although without the signs of myocardial dysfunction on ECHO prior to death. Conclusion Even the application of echocardiographic, biochemical and morphologic techniques hardly gives sufficient grounds to believe that type 1 diabetes alone may actually precipitate myocardial dysfunction, despite long-term course of the disease and typical histological changes in the myocardium.

Topics: Adult; Age Factors; Biomarkers; Cardiomyopathies; Case-Control Studies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Echocardiography; Female; Humans; Hypoglycemic Agents; Insulin; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Sex Factors; Statistics as Topic; Time Factors

We hypothesized that recombinant B-type natriuretic peptide (BNP) (nesiritide) could improve urine output and neurohormonal markers of heart failure without worsening renal function in pediatric patients.. We analyzed our experience involving 140 nesiritide infusions in 63 consecutive children. Serum levels of BNP and electrolytes were measured before and after therapy. Dosing was begun at 0.01 mcg.kg.min without a bolus and titrated to a maximum of 0.03 mcg.kg.min, in 0.005-mcg.kg.min increments. Blood pressure, heart rate, and heart rhythm were monitored. In a substudy, 20 patients with decompensated cardiomyopathy-related heart failure received 72 hours of nesiritide with prospective assessment of aldosterone, norepinephrine, plasma renin, and endothelin-1 levels before and after therapy. The heart rate decreased significantly (P = .001). Urine output increased significantly on Days 1 and 3 (P < or = .001 and .004, respectively). The mean serum creatinine level decreased from 1.135 to 1.007 mg/dL (P < or = .001). In the substudy, aldosterone levels decreased from 37.5 +/- 57.1 to 20.5 +/- 41.9 ng/dL (P = .005). Plasma renin, norepinephrine, and endothelin-1 levels decreased nonsignificantly. Two infusions were discontinued because of hypotension.. Nesiritide safely treated decompensated heart failure in children. Increased urine output reflected improving renal function. Improved neurohormonal markers were seen after 72 hours of therapy, and complications were uncommon.

Topics: Adolescent; Adult; Aldosterone; Biomarkers; Cardiac Output, Low; Cardiomyopathies; Child; Child, Preschool; Creatinine; Diuresis; Endothelin-1; Female; Heart Failure; Heart Rate; Humans; Infant; Infant, Newborn; Kidney; Male; Natriuretic Agents; Natriuretic Peptide, Brain; Norepinephrine; Prospective Studies; Renin; Treatment Outcome

Activation of leukocytes and in particular polymorphonuclear neutrophils (PMN) has emerged as a critical confounder in the pathophysiology of cardiovascular disease: Myeloperoxidase (MPO), one of the principal proteins hosted in and secreted by activated PMN, has been mechanistically linked to endothelial and left ventricular (LV) dysfunction in rodent models of sepsis and ischemic cardiomyopathy. Whether PMN activation is also overt in patients with LV dysfunction of ischemic and nonischemic origin, however, remains elusive. Prospectively, 447 consecutive, stable outpatients were included in this single-center study. In 113 patients with impaired left ventricular function (ejection fraction <50%; nonischemic cardiomyopathy, n=52; ischemic cardiomyopathy, n=61), MPO plasma levels were elevated (24.5 [IR:15.8-54.0] vs 15.5 [IR:8.9-39.2] ng/ml in controls, P<0.01) as was elastase (111.5 [IR:63.8-233.3] vs 70.5 [IR:45.0-129.0] ng/ml, P<0.01) and NT-proBNP plasma levels (747.4 [IR:216.3-1958.3] vs 264.1 [IR:82.5-671.8] ng/L, P<0.01). Elevation of circulating MPO was irrespective of the etiology of heart failure and independent of traditional confounding variables. No association was observed between MPO -463 promoter polymorphism genotype and LV dysfunction. MPO plasma levels correlated with ejection fraction (P<0.01) and left ventricular end-diastolic diameter (P<0.01), respectively. Myeloperoxidase mRNA expression levels obtained from circulating leukocytes were significantly increased in patients with LV dysfunction. Systemic leukocyte activation with increased transcription of MPO mRNA and augmented release of MPO appears to represent a so far underrecognized characteristic in LV dysfunction, which was revealed to be irrespective of the underlying pathology. Given its potent proinflammatory properties, MPO may represent an important mechanistic link to LV dysfunction and deserves to be evaluated as both marker and therapeutic target in this disease.

Topics: Aged; Cardiomyopathies; Female; Humans; Logistic Models; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Neutrophils; Pancreatic Elastase; Peroxidase; Polymorphism, Genetic; Predictive Value of Tests; Prospective Studies; RNA, Messenger; Ultrasonography; Ventricular Dysfunction, Left

In patients with cardiac sarcoidosis, ventricular arrhythmias and/or conduction disturbances are frequently observed and sometimes fatal. However, few reports on disease activity and arrhythmic events in cardiac sarcoidosis are available.. The purpose of this study was to investigate the relationship between disease activity and arrhythmic events in cardiac sarcoidosis and the effect of corticosteroid therapy.. The study population consisted of 15 cardiac sarcoidosis patients with new-onset symptomatic arrhythmia, including eight patients admitted once for complete atrioventricular block (CAVB), five patients admitted once for sustained ventricular tachycardia (VT), and two patients admitted twice for two arrhythmic events (one for CAVB and the other for sustained VT). Disease activity was evaluated by gallium-67 citrate (Ga) scintigraphy. All patients with positive Ga uptake were treated with corticosteroids, and arrhythmic events were evaluated by repeat Holter recordings.. Positive uptake of Ga was observed in 8 (80%) of the 10 CAVB events and in 1 (14%) of the 7 sustained VT events (80% vs 14%, P = .02). Corticosteroids abolished myocardial Ga uptake in all nine patients with positive Ga uptake. After corticosteroid therapy was started, AV conduction improved in 5 of 9 CAVB patients (including 8 patients with new-onset CAVB and one patient with history of CAVB). However, ventricular arrhythmias were not improved after corticosteroid therapy.. In cardiac sarcoidosis patients, CAVB develops mainly during the active phase of the disease. Early treatment with corticosteroids might improve AV conduction disturbance. However, sustained VT is not closely linked with disease activity and frequently develops in the advanced stage of disease.

Topics: Administration, Oral; Adrenal Cortex Hormones; Adult; Aged; Atrioventricular Node; Biopsy; Cardiomyopathies; Citrates; Disease Progression; Drug Administration Schedule; Electrocardiography; Electrocardiography, Ambulatory; Endocardium; Female; Gallium; Heart Block; Hemodynamics; Humans; In Vitro Techniques; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Radionuclide Imaging; Sarcoidosis; Tachycardia, Ventricular

The T-type Ca2+ channel (TCC) is activated, and abnormalities of the TCC may be related to the pathogenesis of Ca2+ overload, in cardiomyopathic hamster hearts. The aims of the present study were to investigate the alteration in expression of the TCC and to examine the effects of a dual L-and T-type Ca2+ channel blocker, efonidipine (EFO), on cardiac function and TCC during development of heart failure in UM-X7.1 cardiomyopathic hamsters.. UM-X7.1 and golden hamsters were examined, and EFO was administered at the age of 20 weeks for 4 weeks. Cardiac function was examined, the expression of TCCalpha1G was measured, and ventricular myocytes were subjected to a patch-clamp study. At 24 weeks, vehicle-treated UM-X7.1 hamsters exhibited significant increases in left ventricular (LV) size, with marked decreases in ejection fraction (LVEF) compared with golden hamsters. In the UM-X7.1 group, the expression of TCCalpha1G increased during development of heart failure compared with the golden hamster group. In the UM-X7.1 group, EFO treatment significantly attenuated the decrease of LVEF without affecting blood pressure compared with the vehicle group. EFO treatment decreased heart rate (by approximately 10%) in both groups. In the golden hamster group, EFO treatment did not affect LV function. The TCC current in ventricular myocytes was significantly increased in UM-X7.1, and was inhibited by EFO in a dose-dependent manner.. In cardiomyopathic hamster hearts, abnormalities in the TCC may be at least in part related to the pathogenesis of abnormal Ca2+ homeostasis, and TCC-blocker treatment may decrease the TCC current, resulting in an improvement of cardiac function. TCC blocker therapy might be a new strategy for certain types of heart failure.

Topics: Animals; Blood Pressure; Calcium Channel Blockers; Calcium Channels, L-Type; Calcium Channels, T-Type; Cardiomyopathies; Cricetinae; Dihydropyridines; Disease Models, Animal; Dose-Response Relationship, Drug; Electrophysiology; Female; Heart Rate; Male; Mesocricetus; Myocytes, Cardiac; Natriuretic Peptide, Brain; Nitrophenols; Organophosphorus Compounds; Patch-Clamp Techniques

Measurement of natriuretic peptides, particularly brain natriuretic peptide (BNP) is an established method for the diagnosis of cardiovascular disorders, chiefly left ventricular (LV) dysfunction. The influence of renal function on the diagnostic utility of natriuretic peptides is unclear.. We performed a cross-sectional study of 296 patients with renal disease but no history of cardiac disease using echocardiography to assess LV mass and function. Circulating levels of atrial natriuretic peptide (ANP) and BNP were also measured.. The incidence of LV hypertrophy increased with progressive renal dysfunction; from 39% in patients with near-normal renal function, to 80% in renal transplant patients. There was a negative correlation between both ANP and BNP, and glomerular filtration rate (GFR) (ANP: r = -0.28, P<0.001; BNP: r = -0.40, P<0.001). Serum ANP and BNP had sensitivity and specificity for LV hypertrophy of 39.9%, 87.4% (ANP) and 61.4%, 67.6% (BNP) respectively. Sensitivity and specificity for LV dysfunction was 77.2%, 32.4% (ANP) and 71.8%, 40.0% (BNP). Significant confounders in determining serum ANP were haemoglobin, beta blockade and albumin, while serum BNP levels were significantly confounded by GFR, albumin, haemoglobin, beta blockade and age.. Across a spectrum of renal dysfunction, GFR is a more important determinant of serum BNP than ventricular function, and several factors are predictors of natriuretic peptide levels. In chronic kidney disease, the use of natriuretic peptides to diagnose LV hypertrophy must be interpreted in light of these other factors. The use of these peptides in renal dysfunction to diagnose LV dysfunction may be of limited value.

Topics: Adult; Atrial Natriuretic Factor; Cardiomyopathies; Chronic Disease; Cross-Sectional Studies; Female; Humans; Hypertrophy, Left Ventricular; Kidney Diseases; Male; Middle Aged; Natriuretic Peptide, Brain

Plasma brain natriuretic peptide (BNP) concentration increases in proportion to heart failure (HF) severity. Although plasma BNP decreases to a certain level by optimal treatment, there is significant heterogeneity in the baseline value among individuals. The underlying mechanism of the steady-state plasma BNP levels remains still controversial. We investigated the hypothesis that myocardial stiffness (K(m)) is a major determinant of the plasma BNP level.. In 19 patients with diastolic HF [DHF; left ventricular ejection fraction (LVEF) > or =4 5%], 18 with systolic HF (SHF; LVEF < 45%), and 12 controls, left ventricular (LV) performance variables and the results of the stress-strain analyses were obtained by the combined simultaneous measurement of echocardiographic and haemodynamic data, and compared with the plasma BNP level. In DHF, a significant correlation was observed between plasma BNP and fractional shortening (P = 0.010), pulmonary capillary wedge pressure (P = 0.030), end-diastolic pressure (P = 0.006), time constant of the LV isovolumic-pressure decline (P = 0.049), end-diastolic stress (P = 0.012), and K(m) (P = 0.004), respectively. In SHF, a significant correlation was observed between plasma BNP and end-diastolic stress (P = 0.036), chamber stiffness (P = 0.048), and K(m) (P = 0.003), respectively.. In stable conditions, K(m) may be the most important determinant of the plasma BNP production in patients with both DHF and SHF.

Topics: Adult; Aged; Aged, 80 and over; Cardiomyopathies; Diastole; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Stroke Volume; Systole

Topics: Adult; C-Reactive Protein; Cardiomyopathies; Female; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders; Recovery of Function

Heart failure secondary to myocardial iron loading remains the leading cause of death in thalassemia major (TM). We used cardiovascular magnetic resonance (CMR) to assess the prevalence of myocardial iron overload and ventricular dysfunction in a large cohort of TM patients maintained on conventional chelation treatment with deferoxamine.. A mobile CMR scanner was transported from London, UK, to Sardinia, Italy where 167 TM patients were assessed for myocardial iron loading, B-natriuretic peptide (BNP), and ferritin. In patients with myocardial iron loading CMR assessments of ventricular function were also made.. Myocardial iron loading (T2* < 20 ms) was present in 108 (65%) patients, which was severe (T2* < 8 ms) in 22 (13%). Impaired (< 56%) left ventricular (LV) ejection fraction (EF) was present in 5%, 20% and 62% of patients with mild, moderate or severe iron loading. Increasing myocardial iron was related to impaired LVEF (Rs = 0.57, p < 0.001), weakly related to serum ferritin (Rs = -0.34, p < 0.001), and not related to liver iron (Rs = 0.11, p = 0.26). BNP was weakly related to myocardial iron (Rs = -0.35, p < 0.001) and was abnormal in only 5 patients.. Myocardial siderosis was found in two-thirds of thalassemia major patients on maintenance deferoxamine treatment. This was combined with a high prevalence of impaired LV function, the severity of which tracked the severity of iron deposition. BNP was not useful to assess myocardial siderosis.

Topics: beta-Thalassemia; Cardiomyopathies; Chi-Square Distribution; Deferoxamine; Female; Ferritins; Humans; Iron Overload; Italy; Magnetic Resonance Imaging; Male; Myocardium; Natriuretic Peptide, Brain; Prevalence; Siderophores; Ventricular Dysfunction, Left

The increase in B-natiuretic peptide (BNP) is well correlated with cardiovascular symptoms in adults. Its use in children is recent and only partially evaluated. The authors undertook a prospective study of BNP concentrations and its kinetics in 54 children with an average age of 15 months (5 days to 11 years) admitted as paediatric emergencies. The symptoms were dyspnoea (60%), shock (15%), suspicion of Kawasaki disease (15%) and other (10%). Twenty children had BNP levels of more than 100 pg/ml related to decompensation of known congenital heart disease in 7 patients (average BNP 462 +/- 323 pg/ml), due to neonatal coarctation in 2 patients (BNP > 3000 pg/ml), due to cardiomyopathy in 6 patients (BNP= 2576 +/- 1215 pg/ml), due to an arrhythmia in 1 patient (BNP= 3754 pg/ml) and to Kawasaki disease in 4 patients (BNP= 521 +/- 448 pg/ml). Thirty-four children had BNP values of less than 100 pg/ml; 29 had no cardiac disease and 5 had known congenital heart disease with other symptoms. Measuring BNP is quick and economical and is a valuable aid in the diagnosis of cardiac dysfunction in symptomatic children in the emergency room. High BNP values seem to be correlated with the severity of the cardiac disease. Low BNP values seem to have a good negative predictive value in children without underlying cardiac disease. The interpretation of intermediary values, especially when there is previous cardiac disease, is more difficult in view of the absence of known threshold values for different haemodynamic situations. Further studies are required to determine the value of this test for the follow-up and setting up of prognostic values in children with congenital heart disease.

Topics: Aortic Coarctation; Arrhythmias, Cardiac; Biomarkers; Cardiac Output, Low; Cardiomyopathies; Child; Child, Preschool; Dyspnea; Emergency Service, Hospital; Heart Defects, Congenital; Humans; Infant; Infant, Newborn; Mucocutaneous Lymph Node Syndrome; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Shock

To determine whether acute left ventricular dysfunction (LVD) causes significantly higher elevation of N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than comparable chronic LVD.. Plasma levels of NT-proBNP were measured in 10 pediatric patients diagnosed with acute LVD, in 7 pediatric patients with stable chronic dilated cardiomyopathy (DCM) and comparable levels of echocardiographic dysfunction, and during 5 episodes of acute exacerbation in patients with heart failure. Levels were compared using Mann-Whitney and analysis of variance for rank tests.. Plasma levels of NT-proBNP were excessively elevated in patients with acute LVD in the first 24 to 48 hours of hospitalization (median level, 65,600 pg/mL), and were significantly higher than those in patients with chronic DCM (median level, 1125 pg/mL; P < .0001). NT-proBNP levels decreased in the subsequent days in 83% of patients with serial measurements. The NT-proBNP levels were lower In 5 episodes of acute exacerbation than in acute LVD (median level, 7185 pg/mL; P < .003).. Acute LVD is associated with elevated NT-proBNP level in children.

Topics: Acute Disease; Adolescent; Adult; Cardiomyopathies; Child; Child, Preschool; Chronic Disease; Heart Failure; Hospitalization; Humans; Infant; Natriuretic Peptide, Brain; Peptide Fragments; Time Factors; Ventricular Dysfunction, Left

The therapeutic potential of anthracycline antibiotics is limited by their cardiotoxicity. Electrocardiography, exercise testing, and two-dimensional echocardiography are non-invasive techniques used in the follow-up of children for cardiotoxicity. Plasma B-type natriuretic peptide (BNP) levels are thought to be useful markers in the early detection of AC induced cardiomyopathy.. We evaluated cardiac status of 34 patients with solid tumors treated with anthracycline antibiotics. All of the patients were asymptomatic and had no evidence of residual malignancy. They were evaluated by electrocardiography, exercise testing, echocardiography, and plasma BNP levels measured before and after the exercise testing.. Electrocardiography revealed only minor abnormalities of little clinical significance. All of the patients completed the exercise testing without complication, and the duration of the exercise for each patient was between normal limits. Cardiac output (CO) and wall stress (WS) were significantly increased in patients, than in controls in echocardiographic evaluation of systolic functions (P < 0.001). Diastolic filling patterns showed various abnormalities; M-E, M-A, T-E, T-A, AT, and IVRT were significantly higher than those of controls. Mean plasma BNP levels of the patients (10.56 +/- 10.22 pg/ml) were significantly higher than BNP levels of the healthy controls (4.09 +/- 2.26 pg/ml) (P < 0.016), before exercise testing. The mean plasma BNP levels of the patients (15.70 +/- 14.06 pg/ml) were higher than resting state after exercise testing, but it was not statistically significant (P > 0.05).. Our findings demonstrated that echocardiographic and biochemical abnormalities could be found even at low cumulative doses of AC antibiotics. The use of serial echocardiographic studies and plasma BNP determinations to identify high-risk patients for cardiotoxicity needs to be verified by additional studies.

Topics: Adolescent; Adult; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cardiomyopathies; Case-Control Studies; Child; Child, Preschool; Echocardiography; Electrocardiography; Exercise Test; Female; Heart Function Tests; Humans; Male; Natriuretic Peptide, Brain; Neoplasms; Prospective Studies; Sensitivity and Specificity; Statistics, Nonparametric; Turkey

Congestive heart failure (CHF) in cardiac amyloidosis has been attributed to the development of diastolic dysfunction, because severe CHF symptoms have been observed despite a normal or only mildly reduced LV ejection fraction (EF). An early impairment of longitudinal systolic function has been described by means of tissue Doppler-derived myocardial deformation imaging ('strain rate imaging', SRI). Our patient presented with signs of CHF and significantly increased brain-natriuretic peptide (BNP) levels. Conventional measures of systolic contractile function were within the normal range and mitral inflow Doppler showed only moderate diastolic dysfunction. Histopathological examination by endomyocardial biopsy revealed interstitial deposition of amyloid fibers. Quantitative assessment of myocardial velocities (TDI) and deformation properties (Strain) from the apical view demonstrated a significant impairement of systolic longitudinal myocardial function. In patients with isolated diastolic dysfunction detected by conventional Doppler echocardiography, the quantitative assessment of myocardial strain and strain rate can be helpful in the early detection of systolic dysfunction.

Topics: Amyloidosis; Biopsy; Cardiomyopathies; Diagnosis, Differential; Diastole; Echocardiography, Doppler; Echocardiography, Doppler, Color; Endocardium; Heart Failure; Humans; Hypertrophy, Left Ventricular; Image Processing, Computer-Assisted; Immunoglobulin Light Chains; Male; Middle Aged; Multiple Myeloma; Myocardial Contraction; Myocardium; Natriuretic Peptide, Brain; Systole; Ventricular Dysfunction, Right

Topics: Animals; Antiviral Agents; Atrial Natriuretic Factor; Cardiomyopathies; Gene Expression Regulation, Viral; Heart; Heart Failure; Hepacivirus; Hepatitis C; Hepatitis C Antibodies; HLA-D Antigens; Humans; Interferons; Mice; Mice, Transgenic; Myocarditis; Myocardium; Natriuretic Peptide, Brain; NF-kappa B; Paraffin Embedding; Phenotype; Prevalence; RNA, Viral; Species Specificity; Transcription Factor AP-1; Viral Core Proteins

The prevalence of left ventricular hypertrophy (LVH), coronary artery disease, and subclinical cardiomyopathy in diabetic patients without known cardiac disease is unclear. We sought the frequency of these findings to determine whether plasma brain natriuretic peptide (BNP) could be used as an alternative screening tool to identify subclinical LV dysfunction.. Asymptomatic patients with diabetes mellitus without known cardiac disease (n = 101) underwent clinical evaluation, measurement of BNP, exercise stress testing, and detailed echocardiographic assessment. After exclusion of overt dysfunction or ischemia, subclinical myocardial function was sought on the basis of myocardial systolic (Sm) and diastolic velocity (Em). Association was sought between subclinical dysfunction and clinical, biochemical, exercise, and echocardiographic variables. RESULTS; Of 101 patients, 22 had LVH and 16 had ischemia evidenced by exercise-induced wall motion abnormalities. Only 4 patients had abnormal BNP levels; BNP was significantly increased in patients with LVH. After exclusion of LVH and coronary artery disease, subclinical cardiomyopathy was identified in 24 of 66 patients. Subclinical disease could not be predicted by BNP.. Even after exclusion of asymptomatic ischemia and hypertrophy, subclinical systolic and diastolic dysfunction occurs in a significant number of patients with type 2 diabetes. However, screening approaches, including BNP, do not appear to be sufficiently sensitive to identify subclinical dysfunction, which requires sophisticated echocardiographic analysis.

Topics: Aged; Cardiomyopathies; Coronary Disease; Diabetes Complications; Diabetes Mellitus, Type 2; Echocardiography, Doppler; Exercise Test; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Ventricular Dysfunction, Left

Topics: Adolescent; Adult; Aged; Autoanalysis; Cardiomyopathies; Female; Fluorescent Antibody Technique; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Point-of-Care Systems; Reference Values

It is not known whether cardiac markers and cyclic variations of integrated backscatter can be used to detect cardiac sarcoidosis.. We studied 62 patients with sarcoidosis affecting the lung, eyes, skin, or heart (27 patients with cardiac involvement and 35 patients without). The cyclic variation of integrated backscatter and wall thickening was evaluated in the left ventricular anterior septum and posterior wall. Plasma A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) concentrations and serum cardiac troponin T were also determined.. Plasma natriuretic peptide concentrations were higher in the cardiac involvement group (ANP: 15.5 [interquartile range (IQR) 2.5-34.0] vs. 12.0 [10.0-16.5] pg/ml, P=0.25; BNP: 28.6 [5.9-141] vs. 10.1 [4.8-15.4] pg/ml, P=0.049). However, cardiac troponin T concentration was <0.01 ng/ml in all patients. Receiver-operator characteristic (ROC) analysis showed that both ANP and BNP could identify patients with high-degree atrioventricular block, ventricular tachyarrhythmias, or symptomatic heart failure (the areas under the ROC curve were 0.94 and 0.97, respectively). The cardiac involvement group could be distinguished from the noninvolvement group by combining cutoff values for the magnitude of integrated backscatter cyclic variation (5.5 dB) and wall thickening (30%), albeit only for the posterior wall.. Both ANP and BNP are useful markers for identifying patients with sarcoidosis and cardiac complication(s). Moreover, evaluation of integrated backscatter cyclic variation combined with wall thickening may be of help in detecting cardiac involvement in the posterior wall.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Echocardiography; Female; Follow-Up Studies; Gated Blood-Pool Imaging; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Retrospective Studies; ROC Curve; Sarcoidosis; Severity of Illness Index; Troponin T

Nesiritide is a recombinant formulation of B-type natriuretic peptide used most commonly in the treatment of adults with decompensated congestive heart failure. The physiologic effects of BNP include natriuresis, diuresis, and smooth muscle relaxation. These physiologic effects result in its beneficial therapeutic effects, including a decrease in afterload, resulting in increased cardiac output with improved peripheral perfusion. The authors report on a 17-year-old with acute myelogenous leukemia who was admitted to the Pediatric ICU for treatment of septic shock, respiratory failure, myocardial dysfunction, and renal insufficiency. After the initial stabilization of his hemodynamic status, nesiritide was started and resulted in a stable balance of fluid intake versus output without the use of diuretics, improvement in myocardial function, and recovery of renal function manifested by a decrease of blood urea nitrogen and creatinine back to baseline values. The end-organ effects of nesiritide, previous reports regarding its use in the pediatric population, and its potential applications in the ICU setting are discussed.

Topics: Adolescent; Cardiomyopathies; Humans; Leukemia, Myeloid, Acute; Natriuretic Peptide, Brain; Renal Insufficiency; Respiratory Insufficiency; Shock, Septic; Treatment Outcome; Water-Electrolyte Balance

Anthracyclines are well established as highly efficacious antineoplastic agents for childhood malignancy, but they frequently cause dose-related cardiotoxicity. For this reason, children who have received anthracyclines need periodical cardiac evaluation. The plasma levels of B-type natriuretic peptide (BNP) have been shown to increase in proportion to severity of cardiac dysfunction. N-terminal BNP (NT-pro-BNP) is secreted from the cardiac ventricles in response to volume expansion and pressure overload. The aim of our study was to investigate whether plasma levels of NT-pro-BNP and cardiac troponin I (cTnI) can be used as specific markers for doxorubicin-induced cardiotoxicity in children with malignancy.. We performed the study in Dicle University Hospital, Pediatric Hematology and Oncology clinic. Were measured plasma NT-pro-BNP and cTnI in 31 patients (14 boys and 17 girls) who received doxorubicin-containing chemotherapy for their malignancy at cumulative doses of 30-600 mg/m2, between October 2000 and December 2004. Cardiac evaluation of the patients included recording of electrocardiography and assessment of systolic and diastolic functions of the heart by echocardiography.. Of the 31 patients, 4 (12.9%) had left ventricular dysfunction as assessed by echocardiography. Plasma NT-pro-BNP levels in these patients were significantly elevated in comparison with healthy controls (p<0.001). Plasma NT-pro-BNP levels were significantly elevated in patients with cardiac dysfunction when compared with normal cardiac function (p<0.008). The cTnI levels were found under normal value in all patients.. Measurement of NT-pro-BNP level may be an easy and practical tool, and during treatment may allow earlier-identification of individuals at risk for monitoring cardiac damage. Plasma NT-pro-BNP concentration may be a useful and sensitive indicator of cardiac dysfunction in children receiving doxorubicin therapy.

Topics: Adolescent; Antibiotics, Antineoplastic; Cardiomyopathies; Case-Control Studies; Child; Child, Preschool; Doxorubicin; Female; Humans; Leukemia; Lymphoma; Male; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I; Ultrasonography

This study sought to determine plasma levels of B-natriuretic peptide (BNP) in patients with light-chain-associated amyloidosis and correlate them with the presence or absence of heart failure (HF) and the presence or absence of echocardiographic abnormalities. Patients with normal echocardiographic results had significantly lower BNP levels than those with echocardiographic features of cardiac amyloidosis, whereas BNP levels in the group with HF did not differ from those in patients with asymptomatic cardiac amyloidosis. This observation supports previous observations, suggesting that the elevation of BNP in cardiac amyloidosis may be due not only to elevated ventricular filling pressure but also to direct myocyte damage due to extracellular deposits of amyloid.

Topics: Amyloidosis; Cardiomyopathies; Echocardiography; Heart Failure; Humans; Middle Aged; Natriuretic Peptide, Brain

The mechanisms of cardiac remodeling during chronic heart failure remain poorly defined. We sought to advance a chronic canine model of nonischemic cardiomyopathy.. Male dogs (n = 6) received decremental right ventricular apical tachypacing (12 months) to achieve and maintain stable left ventricular (LV) dysfunction. After 10 months of tachypacing, 120 beats/min was sufficient to maintain stable LV dysfunction. Electrocardiography, echocardiography, and tissue Doppler imaging were done to evaluate electrophysiology, LV dimensions and function, and dyssynchrony during normal sinus rhythm. The 6-minute walk test was used to evaluate functional capacity. We observed increases in both QRS duration (P < .0001) and QRS amplitude (P < .0001). LV fractional shortening was reduced from a baseline of 38.0 +/- 1.4% to 11.2 +/- 1.4% (P < .0001). LV end-diastolic dimension increased from 3.8 +/- 0.1 cm at baseline to 5.3 +/- 0.3 cm (P < .0001); LV end-systolic dimension increased from 2.3 +/- 0.1 cm to 4.7 +/- 0.2 cm (P < .0001). LV mass increased from 85.9 +/- 3.5 g at baseline to 179 +/- 13.7 g (P < .0001). There was evidence of LV dyssynchrony (P < .04) during both normal sinus rhythm and right ventricular tachypacing, compared with control dogs. The distance a dog walked in 6 minutes was significantly less at 12 months compared with normal controls (540 +/- 32 m versus 277 +/- 64 m, P < .008).. This nonischemic model of canine cardiomyopathy reproduces many aspects of chronic human heart failure including reduced fractional shortening, dilated ventricular dimensions, increased LV mass, decreased functional capacity, and dyssynchrony.

Topics: Animals; Biomarkers; C-Reactive Protein; Cardiomyopathies; Chronic Disease; Disease Models, Animal; Dogs; Echocardiography, Doppler; Electrocardiography; Heart Conduction System; Heart Rate; Humans; Hypertrophy, Left Ventricular; Male; Models, Cardiovascular; Natriuretic Peptide, Brain; Research Design; Stroke Volume; Time Factors; Troponin C; Troponin I; Ventricular Dysfunction, Left; Ventricular Remodeling

Even in high-risk population groups, not all patients have the same risk of sudden cardiac death (SCD). Given the emerging data about the amino-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP) value in heart failure, we planned to evaluate the importance of NT-proBNP levels in predicting the occurrence of malignant arrhythmias in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillators (ICDs).. Prospective study.. Tertiary referral center.. Thirty five ambulatory patients with previous myocardial infarction, left ventricular ejection fraction < 35%, and ICDs for primary prevention of SCD according to Multicenter Automatic Defibrillator Implantation Trial I criteria.. Venous blood samples for plasma NT-proBNP measurement were obtained after 30 min of supine rest from all patients at the beginning of the study. Patients were evaluated every 2 months, or sooner in cases of device discharges, during a 1-year follow-up period. Data concerning arrhythmias and device therapy were stored at the time of device interrogation on each follow-up visit.. During 1-year follow-up, 11 of 35 patients (31.4%) received 18 antiarrhythmic device therapies for ventricular tachyarrhythmia (VT). Patients who experienced such arrhythmias had NT-proBNP levels of 997.27 +/- 335.14 pmol/L (mean +/- SD), whereas those without VT had NT-proBNP levels of 654.87 +/- 237.87 pmol/L (p = 0.001). An NT-proBNP cutoff value of 880 pmol/L had a sensitivity of 73%, a specificity of 88%, a positive predictive value of 80%, and a negative predictive value of 88% for the prediction of occurrence-sustained VT events.. To achieve the maximum benefit by ICD therapy, more precise risk stratification is required, even in high-risk, post-myocardial infarction patients. Plasma NT-proBNP levels comprise a promising method that could help in the better identification of a patient group with an even higher risk of sudden death.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Death, Sudden, Cardiac; Defibrillators, Implantable; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Tachycardia, Ventricular; Ventricular Dysfunction, Left

Brain natriuretic peptide (BNP) is a cardioactive molecule produced in the myocardium. BNP is a sensitive marker of cardiac failure and its measurement in blood could be useful to the diagnosis and the treatment of this disease. Sporting activities, especially endurance ones, can induce cardiac problems, owing to the high workload for the myocardium during long and ultralong heavy effort. There are 2 papers describing the behavior of BNP in endurance events. BNP was elevated in marathoners, immediately after the race and also after 4 h. We studied the behavior of BNP in the triathlon, which is a complex sport characterized by 3 different activities (swimming, cycling, running).. We recruited 49 athletes, all males, except for 4 females; 2 athletes did not finish the race and were not included in the statistical analysis in 2 different competitions. In these subjects we measured BNP using an immunological method before and after a triathlon.. No statistical significance between BNP values, before and after the triathlon, was found.. We found no significant differences between pre- and postcompetition BNP values. Moreover, the range of values in both the blood drawings are similar of those of the general population, representing the biological variability of the analyte. The values in regularly trained athletes,, are not different from the general population and BNP is not modified by a triathlon, a typical endurance sport performance. We can underline that BNP increases in plasma are induced by heavy pathologies and are not influenced by physical activities, even strenuous ones.

Topics: Adult; Bicycling; Biomarkers; Cardiomyopathies; Competitive Behavior; Exercise; Female; Humans; Male; Natriuretic Peptide, Brain; Physical Endurance; Prospective Studies; Running; Sports; Swimming; Time Factors

Clinical methods for the early detection of doxorubicine (adriamycin; ADR) -induced cardiotoxicity have not been established. This study prospectively investigated whether atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and cardiac troponin T (TnT) are predictors for ADR-induced cardiotoxicity, and examined the correlations between the serum concentrations of these biomarkers and the functional alternations associated with ADR-induced myocardial damage.. Male Wistar rats were injected weekly with 2 mg/kg of ADR via the tail vein for 8 weeks to induce cardiotoxicity. Echocardiograms of each ether anesthetized rat were taken at 6, 8, 10 and 12 weeks after the first administration of ADR, and blood samples collected from the tail vein were used to quantify plasma ANP and BNP, and serum TnT after echocardiography. Plasma BNP and serum TnT significantly increased from 6 to 12 weeks (81.5 to 173.3 pg/ml (p<0.001), <0.01 to 1.09 ng/ml (p<0.05), respectively) with deterioration of left ventricular % fractional shortening (%FS) (58.6% to 36.8%). The %FS significantly correlated with TnT (r=-0.51, p<0.001) and BNP (r=-0.75, p<0.0001); however, the increase of TnT was antecedent to the increase of BNP and the deterioration of %FS.. Plasma BNP and serum TnT concentrations, especially TnT, measured by this highly sensitive method are useful predictors for ADR-induced cardiomyopathy.

Topics: Animals; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Disease Progression; Doxorubicin; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Rats; Rats, Wistar; Troponin T; Ventricular Dysfunction, Left

The aim of this study is to determine the cardioprotective efficacy of amifostine. The study consists of researching the relationship between plasma brain natriuretic peptide levels and the electrical and morphologic changes in irradiated rats with or without amifostine.. Sixty Wistar albino rats were divided into 4 groups, and their hearts were given 15 Gy/fraction with (60)Co. In Groups I and II, the rats were killed after 24 hours to detect early effects; in Groups III and IV, the rats were killed 100 days after irradiation to detect late effects. Before irradiation, Groups I and III received 0.9% saline solution, whereas Groups II and IV received amifostine (200 mg/kg). Twenty rats were used as a control group.. On the 100th day, mild myocardial degeneration was detected in 5 rats (33%) from Group III (no amifostine). This percentage was statistically different from that of Group IV (treated with amifostine) and the controls (p = 0.042). There was no statistically significant difference between the mean plasma brain natriuretic peptide values of the groups (p > 0.05). There was no significant difference in electrocardiographies between the groups. There was no correlation between continuous variables.. In the amifostine group (IV) on the 100th day, there was no myocardial degeneration, suggesting that amifostine has a cardioprotective effect.

Topics: Amifostine; Animals; Biomarkers; Cardiomyopathies; Cobalt Radioisotopes; Drug Evaluation, Preclinical; Electrocardiography; Heart; Male; Natriuretic Peptide, Brain; Radiation Dosage; Radiation Injuries, Experimental; Radiation-Protective Agents; Rats; Rats, Wistar

We evaluated the analytical performance of a fully-automated electrochemiluminescence "sandwich" immunoassay method for the N-terminal fragment of the pro-peptide of brain natriuretic peptide (BNP). We then compared the diagnostic accuracy of this method in discriminating between normal subjects and patients with cardiomyopathy with that found with two previously described immunoradiometric assay methods for the assay of atrial natriuretic peptide (ANP) and BNP. We studied 193 consecutive patients (mean age 64.4 +/- 12.3 years, range 20-89 years, including 56 women and 137 men) with chronic cardiomyopathy and a group of 85 healthy subjects (mean age 52.3 +/- 12.0 years, 42 women and 43 men, range 20-79 years). N-terminal fragment of proBNP1-76 (NT-proBNP) was measured with a fully-automated "sandwich" electrochemiluminescence method using an Elecsys 2010 analyzer, while ANP and BNP were measured with immunoradiometric assay methods. The low detection limit of the NT-proBNP assay was 4.2 pg/ml (0.50 pmol/l), while the functional sensitivity was 22 pg/ml (2.60 pmol/l) with a working range (imprecision profile < or = 10% coefficient of variation) extended up to about 30 000 pg/ml (3540 pmol/l). Healthy women (64.3 +/- 41.6 pg/ml, 7.59 +/- 4.91 pmol/l) showed significantly higher values than men (46.9 +/- 30.9 pg/ml, 5.53 +/- 3.64 pmol/l, p = 0.0118). Moreover, age and sex were significantly and independently related to the NT-proBNP values in healthy subjects, as assessed by a multiple linear regression analysis (R = 0.389, F-value = 7.316, P-value = 0.0012). As expected, the NT-proBNP values of patients with cardiomyopathy were significantly higher than those of normal subjects and progressively increased with the severity of heart failure. The respective diagnostic accuracy of the ANP, BNP and NT-proBNP assays in discriminating between the group of normal subjects and that of patients with cardiomyopathy was tested by the response operating characteristic curve analysis. Our data indicated that the NT-proBNP assay is significantly better than either of the ANP or BNP immunoradiometric assays in discriminating affected patients from healthy subjects, especially when only patients with mild disease severity (New York Heart Association class I and II) are considered.

Topics: Adult; Aged; Aged, 80 and over; Atrial Natriuretic Factor; Automation; Cardiomyopathies; Female; Humans; Immunoassay; Immunoradiometric Assay; Linear Models; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors; Reference Standards; Reproducibility of Results; Sensitivity and Specificity

To investigate the value of brain natriuretic peptide plasma levels as a marker of systolic myocardial dysfunction during severe sepsis and septic shock.. Prospective observational study.. Intensive care unit.. A total of 34 consecutive patients with severe sepsis (nine patients) or septic shock (25 patients) without previous cardiac, respiratory, or chronic renal failure.. None.. Myocardial systolic performance was assessed by fractional area contraction (FAC) using echocardiography performed on days 2 (FACD2) and 8. Plasma levels of brain natriuretic peptide were measured at days 1-4 and 8 after the beginning of severe sepsis. Among 34 patients (Simplified Acute Physiology Score II, 43 +/- 2.5), 15 (44%) presented with initial myocardial dysfunction (FACD2 < 50%). Lungs were the origin of sepsis in 65% of patients. The 28-day mortality was 29%. Comparisons were performed between patients with (FACD2 < 50%) and without (FACD2 > or = 50%) myocardial dysfunction. Plasma levels of brain natriuretic peptide were significantly higher in patients with FACD2 < 50% than in those with FACD2 > or = 50% (p <.05) from day 2 to day 4. Brain natriuretic peptide levels were also significantly higher on days 2 and 3 in patients who died during their intensive care unit stay (p <.05).. Systolic myocardial dysfunction is present in 44% of patient with severe sepsis or septic shock. In this setting, brain natriuretic peptide seems useful to detect myocardial dysfunction, and high plasma levels appear to be associated with poor outcome of sepsis, but further studies are needed.

Topics: Analysis of Variance; Biomarkers; Cardiomyopathies; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Observation; Paris; Prognosis; Prospective Studies; Sepsis; Shock, Septic; Survival Analysis

To study whether natriuretic peptide types B (BNP) and A (ANP) reflect clinical signs of heart failure (CSHF) in children with congenital heart defects or cardiomyopathy resulting in different types of haemodynamic situations, such as pressure overload in coarctation of the aorta (CoA), volume overload in ventricular septal defect (VSD) or systolic dysfunction in dilated cardiomyopathy (DCM).. Blood samples for plasma P-BNP and P-ANP were taken before procedures during regular investigation from 26 children (9 CoA, 11 VSD and 6 DCM). The ordinary paediatric cardiologist performed the cardiac evaluation and the data were retrieved from medical charts. CSHF was considered positive if two of the following criteria were fulfilled: reduced physical capacity, feeding disorders, dyspnoea, tachypnoea, hepatomegaly and oedema. The statistical methods were non-parametric.. 0/9 children with CoA, 5/11 with VSD and 6/6 with DCM had CSHF. In children with CSHF, P-BNP and P-ANP were higher, 263 ng l(-1) (range 47.5-1300) and 303 ng l(-1) (range 168-466), than in those without CSHF, 12.3 ng l(-1) (range 4.8-30.8) and 42.9 ng l(-1) (range 13.7-189), respectively (p < 0.001, Mann-Whitney U-test), irrespective of the diagnosis. The same relationship was also found in the group of children with VSD.. Plasma levels of ANP and BNP increase in children with CSHF. This increase is seen irrespective of whether it is due to systolic dysfunction, as in children with DCM, or to a volume overload with a normal systolic function, as in children with VSD.

Topics: Adolescent; Aortic Coarctation; Atrial Natriuretic Factor; Cardiomyopathies; Child; Child, Preschool; Female; Heart Defects, Congenital; Hemodynamics; Humans; Infant; Male; Natriuretic Peptide, Brain

Topics: Angiotensin II; Biomarkers; Cardiac Surgical Procedures; Cardiomyopathies; Heart Failure; Heart Ventricles; Humans; Myocardial Ischemia; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Renin; Stroke Volume; Ventricular Function, Left

Activation of the neuroendocrine axis in congestive heart failure is of prognostic significance, and neurohumoral blocking therapy prolongs survival. The hypothesis that surgical reduction of left ventricular size and function decreases neuroendocrine activation is less established. We evaluated the neurohormonal response to left ventricular reconstruction surgery in ischemic cardiomyopathy.. Norepinephrine, plasma renin activity, and angiotensin II were measured in 10 patients before and 12 months after left ventricular reconstruction. In an additional 5 patients, brain natriuretric peptide was measured before and 3 months postoperatively. Three-dimensional cardiovascular imaging was used to assess ejection fraction and left ventricular end-diastolic volume index.. Concurrent with improvements of New York Heart Association functional class (2.9 +/- 0.5 preoperatively vs 2.0 +/- 0.4 postoperatively, P <.001), ejection fraction (23.9% +/- 6.6% vs 36.2% +/- 6.2%, P <.01), and left ventricular end-diastolic volume index (140.8 +/- 33.8 mL/m(2) vs 90.6 +/- 18.3 mL/m(2), P <.01), considerable reductions were observed for median plasma profiles of norepinephrine (562.0 pg/mL vs 319.0 pg/mL, P <.05), plasma renin activity (5.75 microg/L/h vs 3.45 microg/L/h, P <.05), angiotensin II (41.0 ng/mL vs 23.0 ng/mL, P =.051), and brain natriuretric peptide (771.0 pg/mL vs 266.0 pg/mL, P <.05). The more plasma renin activity or angiotensin II decreased after left ventricular reconstruction, the higher was the increase in ejection fraction (R = -.745, P <.05 [plasma renin activity]; R = -.808, P <.05 [angiotensin II]).. Surgical improvements of ejection fraction and left ventricular end-diastolic volume index by left ventricular reconstruction were accompanied by improvement of both the neuroendocrine activity and the functional status in patients with congestive heart failure. Whether this favorable neurohormonal response is predictive of an improved survival requires further evaluation.

Topics: Aged; Angiotensin II; Biomarkers; Cardiac Surgical Procedures; Cardiomyopathies; Female; Follow-Up Studies; Heart Failure; Heart Ventricles; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Neurotransmitter Agents; Norepinephrine; Renin; Statistics as Topic; Stroke Volume; Treatment Outcome; Ventricular Function, Left

N-terminal pro brain natriuretic peptide (NT-proBNP) is a cardiac biomarker that has recently shown to be of diagnostic value in a diagnosis of decompensated heart failure, acute coronary syndromes and other conditions resulting in myocardial stretch. We sought to study whether sepsis-induced myocardial dilation would result in an elevation of NT-proBNP.. Serum NT-proBNP measurements were made in six consecutive patients with septic shock within 6 hours of admission to the intensive care unit.. Markedly elevated levels of NT-proBNP were found in all six patients.. NT-proBNP levels can be markedly elevated in critically ill patients presenting with septic shock. An elevated NT-proBNP level in a critically ill patient is not specific for decompensated heart failure.

Topics: Adult; Aged; Biomarkers; Cardiomyopathies; Female; Hospital Mortality; Humans; Intensive Care Units; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; ROC Curve; Shock, Septic

Topics: Adult; Aged; Cardiomyopathies; Case-Control Studies; Hemodynamics; Humans; Liver Cirrhosis; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments

The aim of this clinical crossover study was to elucidate the effects of atrioventricular (AV) synchronous pacing on cardiac function in patients with sick sinus syndrome (SSS). Thirty SSS patients, each with dual chamber pacemaker (DDD), were enrolled and divided into two groups based on echocardiographic findings. Group A (n = 16) had hypertensive heart disease (wall thickness 11 approximately 12 mm) or mitral or aortic regurgitation (Grade I or II). Group B (n = 14) had no organic heart disease. Three successive 3-month pacing periods were tested. For the first 3 months, long AV delay that achieved > 80% ventricular sensing was chosen. For the next 3 months, AV delay was abbreviated to achieve > 80% ventricular pacing at an optimal AV interval. For the final 3 months, the first setting was resumed. At the end of each period, M mode echocardiography, pulsed-Doppler study, and measurement of plasma brain natriuretic peptide (BNP) level were conducted. In both groups, echocardiographic parameters were not significantly changed during the evaluation. In group A, plasma BNP level was significantly higher at the end of the short AV delay period than at the long AV delay period (P = 0.009), while in group B it did not differ during each period. AV synchronous pacing (> 80% ventricular pacing) in the SSS patients with a DDD pacemaker implanted could increase the ventricular load, and it is better to preserve the spontaneous QRS with the DDD mode with prolonged AV delay in patients with mild hypertensive or valvular disease.

Topics: Aged; Cardiac Pacing, Artificial; Cardiomyopathies; Echocardiography; Echocardiography, Doppler, Pulsed; Female; Heart Valve Diseases; Humans; Male; Natriuretic Peptide, Brain; Sick Sinus Syndrome

A 75-year-old man without overt heart failure showed an abnormally high level of brain natriuretic peptide (BNP) in plasma: 600 pg/ml. The left ventricular endomyocardial biopsy revealed prominent vacuolar degeneration in the myocytes, most of which were positive for PAS stain and BNP immunoreaction. Ultrastructurally, degenerative changes of myocytes were marked, such as deposits of glycogen and lipofuscin granules in the cytoplasm, but the most prominent finding was giant vacuoles containing degraded mitochondria, glycogen granules, myofibrils, and myelin-like structures (autophagosomes). This case may belong to one of the unclassified cardiomyopathies characterized by prominent autophagic vacuoles.

Topics: Aged; Autophagy; Biopsy; Cardiomyopathies; Heart Failure; Humans; Male; Myocardium; Natriuretic Peptide, Brain

In an unmatched case-control study of 63 non-immune European patients with uncomplicated (n = 52) and complicated (n = 11) falciparum malaria, serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), heart-type fatty acid-binding protein (H-FABP), myoglobin, troponin T and creatin kinase-muscle brain were compared. Elevated levels of NT-proBNP and H-FABP indicated myocardial impairment in complicated but not in uncomplicated falciparum malaria. The clinical impact of these findings remains to be evaluated. The pathophysiology of cardiac impairment in complicated falciparum malaria warrants further investigation.

Topics: Adult; Biomarkers; Blood Proteins; Cardiomyopathies; Carrier Proteins; Case-Control Studies; Creatine Kinase; Creatine Kinase, MB Form; Fatty Acid-Binding Proteins; Humans; Isoenzymes; Malaria, Falciparum; Myoglobin; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Troponin T

Topics: Adult; Aged; Cardiomyopathies; Female; Humans; Immunoenzyme Techniques; Luminescent Measurements; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prognosis

We investigated whether plasma concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) reflect impaired diastolic relaxation or its improvement after ACE inhibition.. 7 long-term Type 1 diabetic patients with normal systolic but impaired diastolic function and with sympathetic myocardial dysinnervation and 10 controls were included. Exercise tolerance and maximal O 2 uptake were evaluated by bicycle exercise prior to the study. ANP, BNP and norepinephrine/epinephrine (NE/E) were determined at baseline and at 80 % .VO2 max workload and after recovery, before and following 12 weeks of treatment with fosinopril (10 mg/d).. Isovolumetric relaxation time (IVRT) and A/E wave ratio were increased by 26.7 +/- 11.5 % and 54.4 +/- 26.1 % in diabetic patients as compared to controls, respectively (p < 0.02). After 12 weeks of fosinopril treatment, no differences in IVRT or A/E wave ratio were detectable between groups. ANP was enhanced in Type 1 diabetes as compared to controls (baseline: 9.2 +/- 3.0 vs. 4.5 +/- 1.1; exercise: 22.4 +/- 7.7 vs. 7.9 +/- 1.2; recovery: 20.3. +/- 4.6 vs. 9.5 +/- 2.0 fmol/ml, p < 0.02). Fosinopril treatment abolished any differences between groups. BNP plasma levels did not differ between groups and no exercise dependent changes were observed. NE- and E-increase was greater at 80 % .VO2 max work load in Type 1 diabetes than in controls (p < 0.05). Again, fosinopril abolished differences between groups.. In Type 1 diabetes, impaired diastolic function is associated with elevated ANP and catecholamine plasma levels that are normalized after ACE inhibition. Thus, ANP but not BNP appears to be a sensitive biochemical marker for early diastolic dysfunction in Type 1 diabetes.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Atrial Natriuretic Factor; Biomarkers; Blood Glucose; Blood Pressure; Body Mass Index; Cardiomyopathies; Diabetes Mellitus, Type 1; Diabetic Angiopathies; Diastole; Female; Fosinopril; Glycated Hemoglobin; Heart; Hemodynamics; Humans; Male; Natriuretic Peptide, Brain

In patients with severe systolic dysfunction the relationship between diastolic dysfunction and plasma levels of atrial and brain natriuretic peptide (ANP, BNP), catecholamines, renin, and aldosterone in patients with chronic heart failure (CHF) has never been investigated.. The aim of this study was to evaluate in clinically stable patients with severe systolic dysfunction whether the presence of diastolic restrictive pattern modifies neurohormonal plasma levels.. Of 82 consecutive patients with stable CHF, 36 were in sinus rhythm, had an adequate ultrasound window and an ejection fraction <30%, and gave their written consent. Plasma levels of ANP, BNP, aldosterone, renin, epinephrine, and norepinephrine were assessed, and the diastolic function was evaluated by Doppler transmitral flow velocity curves.. Except for aldosterone, plasma levels of the other hormones were above normal range in most patients. Patients with restrictive pattern (22%) had BNP plasma levels significantly higher than patients with nonrestrictive pattern (78%): 251 +/- 196 versus 44 +/- 35 ng/L (P=.02). A BNP value of 72.6 ng/L had a sensitivity of 88%, with a specificity of 89% for detecting restrictive pattern in our population.. In clinically stable patients with CHF and severe systolic dysfunction, BNP is the only neurohormone sensitive to the concomitant presence of a restrictive pattern.

Topics: Adult; Aged; Aldosterone; Area Under Curve; Biomarkers; Blood Pressure; Cardiomyopathies; Diastole; Echocardiography, Doppler; Epinephrine; Female; Follow-Up Studies; Heart Failure; Humans; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Predictive Value of Tests; Prognosis; Quality of Life; Renin; ROC Curve; Severity of Illness Index; Statistics as Topic; Stroke Volume; Systole; Ventricular Dysfunction, Left

Growing evidence suggests that the autoimmune mechanism plays an important role in the pathogenesis of dilated cardiomyopathy. The purpose of this study was to evaluate the effect on the cardiac structure and function by the transfer of immunoglobulin G (IgG) and/or lymphocytes from rabbits immunized with a synthetic peptide corresponding to the sequence of the second extracellular loop of beta1-adrenoceptor (beta peptide) into severe combined immunodeficiency (SCID) mice. CB-17 SCID mice were injected intraperitoneally with 2 mg of IgG and/or 1 x 10(7) peripheral blood lymphocytes (PBL) from either rabbits immunized with both beta1 peptide and adjuvant (beta group), and adjuvant or rabbits with adjuvant only (N group). Thirty-five SCID mice were divided into seven groups: (1) N-IgG group; (2) N-PBL group; (3) N-IgG+PBL group; (4) beta-IgG group; (5) beta-PBL group; (6) beta-IgG+PBL group; and (7) control group. Morphological, serological and endocrinological studies were performed 70 days after the transfer. Results showed that heart weight and heart weight/body weight ratio in the beta-IgG+PBL group tended to be increased as compared with those in other groups. All mice in the beta-IgG group, two in the beta-PBL group and four in the beta-IgG+PBL group showed high titer of rabbit anti-beta1-adrenoceptor antibodies. Brain natriuretic peptide in the beta-IgG+PBL group showed a significant increase as compared with those in the control group and N-IgG+PBL. Pathohistologically, focal infiltration of inflammatory cells in the myocardium was observed in one mouse of the beta-IgG+PBL group. Rabbit CD3-positive T-lymphocytes in the myocardium were observed in two mice of the beta group. In conclusion, transfer of IgG and PBL from rabbits immunized with beta1 peptide was able to induce the early stages of myocardial damage in SCID mice. These data provide direct evidence that the autoimmune mechanism is important in the pathogenesis of dilated cardiomyopathy.

Topics: Adoptive Transfer; Animals; Autoantibodies; Autoimmune Diseases; Body Weight; Cardiomyopathies; Disease Models, Animal; Female; Heart; Immunoglobulin G; Injections, Intraperitoneal; Lymphocyte Transfusion; Male; Mice; Mice, SCID; Myocardium; Natriuretic Peptide, Brain; Organ Size; Rabbits; Receptors, Adrenergic, beta-1; Severe Combined Immunodeficiency; T-Lymphocytes

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones that regulate blood pressure and volume, and exert their biological actions via the natriuretic peptide receptor-A gene (Npr1). Mice lacking Npr1 (Npr(-/-)) have marked cardiac hypertrophy and fibrosis disproportionate to their increased blood pressure. This study examined the relationships between ANP and BNP gene expression, immunoreactivity and fibrosis in cardiac tissue, circulating ANP levels, and ANP and BNP mRNA during embryogenesis in Npr1(-/-) mice. Disruption of the Npr1 signaling pathway resulted in augmented ANP and BNP gene and ANP protein expression in the cardiac ventricles, most pronounced for ANP mRNA in females [414 +/- 57 in Npr1(-/-) ng/mg and 124 +/- 25 ng/mg in wild-type (WT) by Taqman assay, P < 0.001]. This increased expression was highly correlated to the degree of cardiac hypertrophy and was localized to the left ventricle (LV) inner free wall and to areas of ventricular fibrosis. In contrast, plasma ANP was significantly greater than WT in male but not female Npr1(-/-) mice. Increased ANP and BNP gene expression was observed in Npr1(-/-) embryos from 16 days of gestation. Our study suggests that cardiac ventricular expression of ANP and BNP is more closely associated with local hypertrophy and fibrosis than either systemic blood pressure or circulating ANP levels.

Topics: Animals; Atrial Natriuretic Factor; Cardiomegaly; Cardiomyopathies; Embryo, Mammalian; Female; Fibrosis; Guanylate Cyclase; Heart Ventricles; Hypertension; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Myocardium; Natriuretic Peptide, Brain; Receptors, Atrial Natriuretic Factor; Reference Values; RNA, Messenger

An 80-year-old female was admitted for a persistent consciousness disturbance. Electrocardiography revealed ST-segment elevation in leads II, III, aVf, and V3-V6. Coronary angiography demonstrated normal arteries, while left ventriculography revealed asynergy of apical akinesis and basal hyperkinesis. The creatinine kinase and creatinine kinase MB levels were not elevated after the initial measurement on admission. The diffuse ST-segment elevation reached a maximum level 24 hours after admission. In leads V3-V6, ST-segment elevation continued for 48 hours, and was followed-up by deep inverted T waves. Within 24 days, the asynergy improved without any specific treatment, but the giant negative T waves were present on the electrocardiogram. The plasma norepinephrine and brain natriuretic peptide levels on the first hospital day were 2.9ng/mL and 906pg/mL, respectively. The left ventricular dysfunction appeared to be induced by the exposure to high-level plasma catecholamines. (123)I-metaiodobenzyl guanidine scintigraphy also revealed transient dysfunction of the cardiac catecholamine dynamics.

Topics: Aged; Aged, 80 and over; Biomarkers; Cardiomyopathies; Catecholamines; Electrocardiography; Female; Humans; Natriuretic Peptide, Brain; Norepinephrine; Ventricular Dysfunction, Left

The brain natriuretic peptide (BNP) assay is a new, relatively inexpensive, and simple test that has the potential to be an early, cost-effective, and reliable marker for HIV-related cardiomyopathy. We report 1 case of HIV-related cardiomyopathy and 10 cases of of HIV infection with unknown heart disease in which we measured BNP levels and performed echocardiography. We found a significant inverse relationship between BNP and left ventricular function in these patients. Further basic and epidemiologic research on BNP measurement for the detection of HIV-related cardiomyopathy is needed to support these findings, which if confirmed, could have important clinical and public health implications.

Topics: Adult; Biomarkers; Cardiomyopathies; Case-Control Studies; Echocardiography; Female; HIV Infections; Humans; Male; Middle Aged; Natriuretic Peptide, Brain

The natriuretic hormones ANP and BNP are expressed differently in the myocardium. Both hormones have compensatory diuretic activity during heart failure. Mechanical stretch of the myocardial walls induces the expression of these hormones. In failing human myocardium, both ANP and BNP are transcribed in the ventricular myocardium in high amounts. We measured the plasma concentrations of ANP and BNP in patients supported by various ventricular assist devices (VADs) at various times. We analyzed the time courses of ANP and BNP to determine (1) the time scale of their down-regulation as a marker of putative myocardial recovery, (2) their steady-state levels under VAD support and (3) differences caused by various VAD devices.. We analyzed ANP and BNP using commercially available radioimmune assays. We analyzed the time courses of patients supported by Thoratec (THO) LVAD (n = 8), TCI Heartmate (TCI) (n = 6), Novacor (NOV) (n = 7), and Lionheart (LIO) (n = 3).. Patients supported with NOV and some patients with TCI showed down-regulation of BNP to a steady-state level at 30 to 50 days, following a single exponential decay. In contrast, patients supported by THO or LIO did not reveal a determined time course of the natriuretic hormones. Only a few patients reached normal plasma values during VAD support.. The time courses of ANP and BNP differ among VAD types because of construction and/or driving mode, which might be important when considering patients for weaning from VAD without heart transplant.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Heart Transplantation; Heart-Assist Devices; Humans; Middle Aged; Myocardium; Natriuretic Agents; Natriuretic Peptide, Brain; Predictive Value of Tests; Time Factors

Long term effects of left ventricle (LV) repair surgery (LVR) for ischemic cardiomyopathy are not well understood.. Sixty-nine rats developed ischemic cardiomyopathy with large akinetic LV area 4 weeks after the left anterior descending artery was ligated. In a second surgery 4 weeks later, 33 rats underwent LVR by plication of the akinetic LV area (LVR group), and 36 underwent rethoracotomy alone (sham group). No medication was used in either group. All rats survived the second surgery. LV end-diastolic dimension as measured by echocardiography, LV fractional shortening, and the maximal end-systolic pressure-volume relationship (E(max)) as calculated from the data by catheter-tipped manometer and echocardiography improved in the LVR group after the second surgery, but LV end-diastolic dimension and E(max) gradually deteriorated as time passed. LV end-diastolic pressure improved 1 week after LVR but rose significantly 4 weeks after LVR. Brain natriuretic peptide mRNA was lower in the LVR group than in the sham group 1 week after LVR but not 4 weeks postoperatively.. Initial improvement in LV function and neurohormonal status after LVR did not last for 4 weeks in this rat model when untreated medically. The mechanism of deterioration should be elucidated to improve long-term results of LVR.

Topics: Animals; Cardiac Surgical Procedures; Cardiomyopathies; Disease Models, Animal; Disease Progression; Echocardiography; Heart Ventricles; Hemodynamics; Male; Myocardial Ischemia; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; RNA, Messenger; Stroke Volume; Time; Treatment Failure; Ventricular Dysfunction, Left

The left ventricular assist system (LVAS) has been used increasingly for patients with end-stage heart failure who are awaiting transplantation. Sympathetic nerve activity is known to correlate with cardiac function in chronic heart failure patients, but little is known about sympathetic nerve activity during LVAS support. In this study, we examined the status of sympathetic nerve activity in relation to mechanical support.. In this study, we included 10 consecutive patients with end-stage cardiomyopathy who were on LVAS support for at least 2 months (duration, 222 +/- 59 days). None of these patients achieved enough functional recovery to be taken off LVAS. In these patients, we used iodine-125-metaiodobenzylguanidine (125I-MIBG) scintigraphy to examine the change of sympathetic nerve activity after LVAS implantation, and compared the results with the change of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels as well as with histologic optional findings. Samples for ANP and BNP measurement were obtained before and 30 days after LVAS implantation. Specimens for histologic analysis were obtained at the time of LVAS implantation and at the time of cardiac transplantation or autopsy.. We observed marked decrease in serum levels of ANP and BNP 1 month after LVAS implantation. But myocardial sympathetic nerve function, which was evaluated with 125I-MIBG scintigraphy and expressed as the heart-to-mediastinum activity ratio, remained below normal even 2 months after the LVAS implantation (1.57 +/- 0.19; normal, 2.34 +/- 0.36). Serial histologic analysis in these 10 patients showed continuous increase in percentage of fibrosis and cell diameter despite ventricular unloading by the LVAS.. Sympathetic nerve function, which was evaluated on 125I-MIBG scintigraphy, did not improve during left ventricular support. Because none of the patients included in our study showed improvement in cardiac function or histologic findings, the recovery of myocardial sympathetic nerve function may be an important factor in myocardial recovery for cardiomyopathy patients on LVAS support.

Topics: 3-Iodobenzylguanidine; Adult; Atrial Natriuretic Factor; Cardiomyopathies; Echocardiography; Female; Heart Failure; Heart-Assist Devices; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Radionuclide Imaging; Radiopharmaceuticals; Sympathetic Nervous System

Subtle cardiac abnormalities have been described in patients with cirrhosis. Natriuretic peptide hormones have been reported to be sensitive markers of early cardiac disease. We postulate that plasma levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide could be used as markers of cardiac dysfunction in cirrhosis. The aim of the study was to evaluate the levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide and their relationship with cardiac structure and function in patients with cirrhosis. The study population comprised 36 patients with cirrhosis of mixed aetiologies, but with no cardiac symptoms; 19 of the patients had ascites and 17 did not. The subjects underwent (i) trans-thoracic two-dimensional echocardiography, and (ii) radionuclide angiography for measurements of cardiac structural parameters, diastolic and systolic function. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were also measured. The results were compared with those from eight age- and sex-matched healthy volunteers. Compared with the controls, the baseline mean ejection fraction was increased significantly in both patient groups (P=0.02), together with prolonged deceleration times (P=0.03), left atrial enlargement (P=0.03) and interventricular septal thickening (P=0.02), findings that are compatible with diastolic dysfunction. Levels of N-terminal pro-atrial natriuretic peptide and brain natriuretic peptide were significantly higher in all patients with cirrhosis with ascites (P=0.01 and P=0.05 respectively), but in only some of the pre-ascitic cirrhotic patients, compared with controls. All high levels of brain natriuretic peptide were correlated significantly with septal thickness (P<0.01), left ventricular diameter at the end of diastole (P=0.02) and deceleration time (P<0.01). We conclude that elevated levels of brain natriuretic peptide are related to interventricular septal thickness and the impairment of diastolic function in asymptomatic patients with cirrhosis. Levels of brain natriuretic peptide may prove to be useful as a marker for screening patients with cirrhosis for the presence of cirrhotic cardiomyopathy, and thereby identifying such patients for further investigations.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Diastole; Female; Heart Septum; Humans; Liver Cirrhosis; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Protein Precursors; Systole

We investigated the expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their genes in the hearts of patients with cardiac amyloidosis and those with isolated atrial amyloidosis.. The expression of ANP and BNP is augmented in the ventricles of failing or hypertrophied hearts, or both. The expression of ANP and BNP in the ventricles of hearts with cardiac amyloidosis, which is hemodynamically similar to restrictive cardiomyopathy, is not yet known. ANP is the precursor protein of isolated atrial amyloid.. We analyzed the immunohistocytochemical localizations of ANP and BNP as well as the expression of their mRNAs by in situ hybridization in the myocardium and measured the plasma levels of ANP and BNP in patients with cardiac amyloidosis.. Four of the five right and all six left ventricular endomyocardial biopsy specimens obtained from six patients with cardiac amyloidosis were immunohistochemically positive for both ANP and BNP; none of the biopsy specimens from eight normal subjects were positive for ANP or BNP. All four of the right atria obtained at operation showed positive immunoreactions for both peptides. Electron microscopy identified specific secretory granules in ventricular myocytes of the patients with cardiac amyloidosis, but not in ventricular myocytes from the normal control subjects. Double immunocytochemical analysis revealed the co-localization of ANP and BNP in the same granules and that isolated atrial amyloid fibrils were immunoreactive for ANP and BNP, whereas ventricular amyloid fibrils were negative for both peptides. Both ANP mRNA and BNP mRNA were expressed in the ventricles of the patients with cardiac amyloidosis but not in the normal ventricles. The autopsy study of four patients with cardiac amyloidosis revealed an almost transmural distribution of ANP and BNP, with predominance in the endocardial side. Plasma BNP levels in the patients were markedly elevated ([mean +/- SD] 1,165.1+/-561.2 pg/ml) compared with those in the control subjects (8.9+/-6.0 pg/ml, p < 0.05).. Expression of ANP and BNP and their genes was augmented in the ventricular myocytes of the patients with cardiac amyloidosis. Both regional mechanical stress by amyloid deposits and hemodynamic stress by diastolic dysfunction may be responsible for the expression of the peptides in patients with cardiac amyloidosis.

Topics: Aged; Amyloidosis; Atrial Natriuretic Factor; Cardiomyopathies; Cytoplasmic Granules; Endocardium; Female; Gene Expression; Heart Ventricles; Humans; Immunohistochemistry; In Situ Hybridization; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; RNA, Messenger

The level of plasma brain natriuretic peptide (BNP) was elevated in 8 of 15 female gene carriers of Duchenne muscular dystrophy (DMD), and the level correlated with indices of cardiac function. In one of these carriers, whose clinical course was followed for one year, the plasma BNP level was elevated before the development of cardiac symptoms, further increased with the evolution of cardiac symptoms, and then decreased after treatment for cardiac failure. These results suggest that the plasma BNP level may be useful for the early detection of cardiac dysfunction and for evaluating the efficacy of cardiac treatment in female DMD carriers.

Topics: Adult; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathies; Female; Heterozygote; Humans; Middle Aged; Muscular Dystrophies; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Various alterations in the natriuretic peptide system have been observed in heart and plasma in humans and animals with heart failure. However, there is limited information about these hormones in hamster lung especially in those with genetic cardiomyopathy, a model of human congestive heart failure. Therefore, the aim of the present study was to investigate the content of the three natriuretic peptides (atrial natriuretic peptide (ANP); brain natriuretic peptide (BNP); C-type natriuretic peptide (CNP) and their gene expression in lungs of normal and cardiomyopathic hamsters. The presence of mRNA coding for ANP and BNP in lungs and heart was investigated by Northern blot and confirmed by reverse transcription polymerase chain reaction (RT-PCR). The peptide contents and plasma concentrations were determined by specific radioimmunoassays. Plasma ANP increased in hamsters with moderate to severe cardiomyopathy (aged 230 days) from control levels of 71.8+/-15.8 to 243.1+/-44.0 pg/ml (P < 0.01). Plasma BNP also increased from 79.7+/-23.5 to 227.9+/-51.6 pg/ml (P < 0.01). The levels of the three peptides in lungs of 30- and 120-day-old cardiomyopathic (CMO) hamsters were not different from their corresponding age-matched controls. However, lung ANP increased in 230-day-old CMO from 589+/-63 to 1624+/-219 pg/mg protein (P < 0.01). Lung BNP and CNP also increased from 332+/-35 to 531+/-55 pg/mg protein (P < 0.01) and from 118+/-21 to 224+/-29 pg/mg protein (P < 0.01), respectively. Lung ANP mRNA and BNP mRNA were significantly (P < 0.05) higher in 230-day-old hamsters than those detected in age-matched normal controls. Our data demonstrate that the hamster lungs produce ANP, BNP and CNP, and that this production is enhanced in moderate to severe cardiomyopathy. These findings imply that the lung natriuretic peptide system may participate in pulmonary function especially during cardiac dysfunction.

Topics: Animals; Atrial Natriuretic Factor; Cardiomyopathies; Cricetinae; Lung; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Nerve Tissue Proteins; Polymerase Chain Reaction; Proteins; RNA, Messenger

Ventricular concentrations of atrial, brain (BNP) and C-type natriuretic peptide are enhanced in congestive heart failure (CHF). Natriuretic peptide receptors are present on ventricular myocytes and stimulate guanosine 3',5'-cyclic monophosphate (cGMP) production. cGMP has been demonstrated to affect myocyte function in vitro. Thus we hypothesized that the intracardiac natriuretic peptide system may modulate myocardial and coronary function in CHF. To test this hypothesis, the effects of an intracoronary infusion of the natriuretic peptide receptor antagonist HS-142-1 on ventricular and coronary function were examined in anesthetized dogs with chronic CHF. To determine whether receptor stimulation had contrasting effects to those of receptor blockade, intracoronary BNP was infused in anesthetized normal and CHF dogs. Low-dose HS-142-1 delayed and slowed left ventricular (LV) relaxation and decreased coronary blood flow without changes in LV pressures. Higher doses further impaired LV relaxation without further decreases in coronary blood flow. In normal and CHF dogs, exogenous BNP produced the opposite effect with a quicker onset and faster rate of LV relaxation without effects on LV pressures or coronary blood flow. The endogenous natriuretic peptide system has an autocrine-paracrine role to modulate LV and coronary vascular function in CHF.

Topics: Adrenergic beta-Antagonists; Animals; Blood Pressure; Cardiac Output; Cardiomyopathies; Coronary Circulation; Coronary Vessels; Cyclic GMP; Dogs; Heart Failure; Heart Rate; Hemodynamics; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Polysaccharides; Propanolamines; Receptors, Atrial Natriuretic Factor; Tachycardia; Vascular Resistance; Ventricular Function, Left

Brain and atrial natriuretic peptides (BNP and ANP) are cardiac hormones with diuretic, natriuretic, and vasodilatory activities. Cardiomyopathic hamsters are widely used animal models of heart failure. Due to the structural divergence of BNP among species, examination on pathophysiological roles of BNP using cardiomyopathic hamsters is so far impossible. We therefore isolated hamster BNP and ANP cDNAs, and investigated synthesis and secretion of these peptides in normal and cardiomyopathic hamsters. The COOH-terminal 32-residue peptide of cloned hamster preproBNP with 122 amino acids, preceded by a single arginine residue, supposedly represents hamster BNP showing < 50% homology to rat BNP. Alpha-hamster ANP, 28-residue peptide, is identical to alpha-rat ANP. In hamsters, BNP and ANP occur mainly in the ventricle and the atrium, respectively. The 32-wk-old hypertrophic cardiomyopathic BIO14.6 strain exhibited ventricular hypertrophy. The 32-wk-old dilated cardiomyopathic BIO53.58 strain remained at the stage without apparent heart failure. In BIO14.6 and BIO53.58 strains at this age, ventricular BNP and ANP gene expressions are augmented, and the plasma BNP concentration is elevated to 136 and 108 fmol/ml, respectively, three times greater than the elevated plasma ANP concentration, which well mimics changes of the plasma BNP and ANP concentrations in human heart failure. Cardiomyopathic hamsters, therefore, are useful models to investigate the implication of BNP in human cardiovascular diseases.

Topics: Amino Acid Sequence; Animals; Atrial Natriuretic Factor; Base Sequence; Blotting, Northern; Cardiomyopathies; Cloning, Molecular; Conserved Sequence; Cricetinae; DNA Primers; DNA Probes; DNA, Complementary; Gene Expression; Heart Atria; Heart Ventricles; Humans; Mesocricetus; Mice; Molecular Sequence Data; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Polymerase Chain Reaction; Rats; Restriction Mapping; RNA, Messenger; Sequence Homology, Amino Acid

Atrial amyloid deposits are common in the ageing human heart and contain alpha-atrial natriuretic peptide (proANP99-126) immunoreactivity. However, atrial myocytes secrete both amino and carboxy terminal fragments of the ANP prohormone (proANP1-126) and also express an homologous, but separate brain natriuretic peptide (BNP). Characteristic amyloid deposits were identified in the atria of 9/22 patients (26-63 years of age) with end-stage heart failure. Amyloid fibrils displayed immunoreactivity for both amino and carboxy terminal fragments of proANP1-126 and for the distinct BNP sequence. As in other endocrine organs, both mature and precursor peptide sequences appear to be constituents of amyloid fibrils. Whilst immunoreactivity for cardiac peptide hormones is co-localized in atrial amyloid deposits, it is uncertain whether the increase in natriuretic peptide expression which accompanies cardiac failure contributes to the incidence of isolated atrial amyloidosis.

Topics: Adolescent; Adult; Amyloid; Amyloidosis; Atrial Natriuretic Factor; Cardiomyopathies; Coronary Disease; Female; Heart Atria; Heart Diseases; Heart Valve Diseases; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Muscle Proteins; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Protein Precursors