cardiovascular-agents and Myocarditis

Myocardial infarction (MI) in the absence of obstructive coronary artery disease (MINOCA) is prevalent in around 5% of acute myocardial infarction (AMI) presentations. MINOCA is a heterogeneous entity with many different etiologies. It is important for health care providers to familiarize themselves with the disease process, presentation, and possible underlying causes in order to guide appropriate management strategies. In this article, the authors review the contemporary definition, etiologies and assessment, and management for AMI patients with MINOCA.

Topics: Aortic Dissection; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Coronary Artery Disease; Coronary Circulation; Coronary Vasospasm; Coronary Vessels; Humans; Myocardial Infarction; Myocarditis; Platelet Aggregation Inhibitors; Risk Factors; Severity of Illness Index; Takotsubo Cardiomyopathy; Thromboembolism

Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.

Topics: Algorithms; Biomarkers; Biopsy; Cardiovascular Agents; Defibrillators, Implantable; Electrocardiography; Endocardium; Giant Cells; Heart; Heart Transplantation; Heart-Assist Devices; Humans; Immunosuppressive Agents; Myocarditis; Natriuretic Peptide, Brain; Troponin I

The morbidity of myocarditis demonstrates an upward tendency by years, is commonly defined as the inflammation of myocytes and is caused by multiple factors. With the development of the molecular biological technique, great breakthroughs in the diagnosis and understanding of pathophysiological mechanisms of myocarditis have recently been achieved. Several questions remain unresolved, however, including standard treatment approaches to myocarditis, which remain controversial and ambiguous. Heart rate, as an independent risk factor, has been shown to be related to cardiac disease. Recent studies also show that the autonomic nervous system is involved in immunomodulatory myocarditis processes. Heart rate reduction treatment is recommended in myocarditis based on a number of animal experiments and clinical trials. It is possible that heart rate-lowering treatments can help to attenuate the inflammatory response and myocyte injury and reverse ventricular remodeling. However, how to execute the protective effects of heart rate reduction on myocarditis is still not clear. In this review, we discuss the pathogenesis and pathophysiological process of viral myocarditis and propose heart rate lowering as a therapeutic target for myocarditis, especially in light of the third-generation β-blockade carvedilol and funny channel blocker ivabradine. We also highlight some additional beneficial effects of such heart rate reduction agents, including anti-inflammatory, antioxidation, anti-nitrosative stress, anti-fibrosis and antiapoptosis properties.

Topics: Adrenergic beta-Antagonists; Animals; Cardiovascular Agents; Carvedilol; Heart Rate; Humans; Inflammation; Ivabradine; Myocarditis

Chagas cardiomyopathy is an emerging form of non-ischemic cardiomyopathy in the USA. This review aims to summarize current concepts in pathophysiology, disease transmission, medical therapy, and heart transplantation for patients with chronic Chagas cardiomyopathy.. The incidence of Chagas cardiomyopathy is increasing in the USA, driven mainly by immigration from countries where Chagas disease is endemic. Chagas cardiomyopathy is a chronic, progressive myocarditis, with hallmark features of biventricular dysfunction, ventricular arrhythmias, thromboembolic complications, and a high risk of mortality. Currently, there is no effective treatment for chronic Chagas cardiomyopathy. Heart transplantation is the only treatment for patients with end-stage Chagas cardiomyopathy, but is associated with unique challenges including risk of reactivation. As the prevalence of Chagas cardiomyopathy increases in the USA, practitioners must be aware of the unique challenges in diagnosis and management that Chagas cardiomyopathy presents.

Topics: Cardiovascular Agents; Chagas Cardiomyopathy; Chagas Disease; Heart Transplantation; Humans; Myocarditis; Risk Factors; Treatment Outcome; Trypanocidal Agents; Trypanosoma cruzi; United States

Mammalian target of rapamycin (mTOR) is an evolutionary conserved kinase that senses the nutrient and energy status of cells, the availability of growth factors, stress stimuli and other cellular and environmental cues. It responds by regulating a range of cellular processes related to metabolism and growth in accordance with the available resources and intracellular needs. mTOR has distinct functions depending on its assembly in the structurally distinct multiprotein complexes mTORC1 or mTORC2. Active mTORC1 enhances processes including glycolysis, protein, lipid and nucleotide biosynthesis, and it inhibits autophagy. Reported functions for mTORC2 after growth factor stimulation are very diverse, are tissue and cell-type specific, and include insulin-stimulated glucose transport and enhanced glycogen synthesis. In accordance with its cellular functions, mTOR has been demonstrated to regulate cardiac growth in response to pressure overload and is also known to regulate cells of the immune system. The present manuscript presents recently obtained insights into mechanisms whereby mTOR may change anabolic, catabolic and stress response pathways in cardiomocytes and discusses how mTOR may affect inflammatory cells in the heart during hemodynamic stress. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel.

Topics: Animals; Cardiomegaly; Cardiovascular Agents; Humans; Inflammation Mediators; Myocarditis; Myocytes, Cardiac; Protein Biosynthesis; Protein Kinase Inhibitors; Proteolysis; Signal Transduction; TOR Serine-Threonine Kinases; Ventricular Remodeling

Heart failure (HF) is a clinical syndrome characterized by dyspnea, fatigue, and poor exercise capacity due to insufficient cardiac function. HF represents the leading cause of hospitalization among adult patients over 65 years of age. Neurohormonal blockade has improved clinical outcomes; however, HF incidence continues to rise, suggesting an urgent need to develop novel drugs that target a different pathophysiological paradigm. Inflammation plays a central role in many cardiovascular diseases. Interleukin-1 (IL-1), a prototypical proinflammatory cytokine, is upregulated in HF and associated with worse prognosis. Preclinical models suggest a beneficial effect of IL-1 blockade, and pilot clinical trials are currently underway to evaluate the role of IL-1 blockade to reduce inflammation, ameliorate ventricular remodeling, and improve exercise capacity in patients with HF.

Topics: Cardiovascular Agents; Heart Failure; Humans; Inflammation Mediators; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Myocardial Infarction; Myocarditis; Ventricular Remodeling

Idiopathic giant cell myocarditis (IGCM) is a rare disease causing progressive myocarditis characterized by myocardial necrosis and giant cells. Patients often present with rapidly progressive heart failure, ventricular arrhythmias, and heart block. Without treatment, the disease often results in progressive pump failure requiring urgent cardiac transplantation or the need for mechanical circulatory support. The underlying pathophysiologic mechanisms are not yet defined but appear to involve genetics, autoimmune disorders, and possibly environmental factors such as viruses. Combined immunosuppressive regimens appear to prolong survival from death or cardiac transplant. Nevertheless, cardiac transplant is an effective treatment. The disease can recur in the transplanted heart resulting in death or the need for retransplant.

Topics: Cardiovascular Agents; Giant Cells; Heart Transplantation; Heart-Assist Devices; Humans; Myocarditis; Rare Diseases

An overview of pericarditis, cardiomyopathy, and acute myocarditis is presented. Clinical presentation, causes, physical signs, laboratory testing, and various imaging procedures are discussed. Established pharmacologic and mechanical therapies are reviewed. Short-term and long-term prognoses, when relevant, are discussed.

Topics: Acute Disease; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Cardiac Resynchronization Therapy; Cardiomyopathies; Cardiovascular Agents; Defibrillators, Implantable; Echocardiography; Electrocardiography; Humans; Myocarditis; Pericardial Effusion; Pericarditis

The treatment of progressive and terminal heart failure follows the principle of causative therapy. Therefore, etiology and pathophysiology of the underlying disease and its hemodynamic conditions are indispensable. This applies to coronary artery disease, hypertension, valvular heart disease, the cardiomyopathies with and without inflammation, and microbial persistence similarly. The classic treatment algorithms both in heart failure with and without reduced ejection fraction are based on measures onloading the heart (angiotensin-converting enzyme inhibitors, angiotensin antagonists, beta-blockers, diuretics) and on antiarrhythmics and anticoagulation, when needed. Device therapy for cardiac resynchronization in left bundle branch block and permanent stimulation therapy may contribute to the hemodynamic benefit. ICD (implantable cardioverter defibrillator) therapy prevents sudden cardiac death, which is often associated with progressive heart failure. Heart transplantation and left ventricular assist devices are final options in the treatment repertoire of terminal heart failure.

Topics: Biopsy; Cardiac Output, Low; Cardiovascular Agents; Defibrillators, Implantable; Evidence-Based Medicine; Heart Failure; Heart Transplantation; Heart-Assist Devices; Humans; Myocarditis; Myocardium; Prognosis; Randomized Controlled Trials as Topic

Concealed undiagnosed congenital anomalies of coronary arteries (CACA) can cause sudden death of young men. Isolated CACA are detected at 0.6-1.8% of coronary angiographies. Classification of CACA (2002) includes anomalous origin of coronary artery from pulmonary artery, anomalous origin of coronary artery from the aorta, congenital atresia of the left main coronary artery, coronary arteriovenous fistula, coronary artery with myocardial bridge, coronary artery aneurism, coronary artery stenosis. In most cases coronary artery anomalies for long time remain asymptomatic. Clinical picture of anomalous origin of coronary artery from pulmonary artery is often erroneously related to cardiomyopathy or myocarditis because of signs of heart failure. Modern methods of visualization are used for diagnosis of CACA: echocardiography (transthoracic and transesophageal), computer angiotomography (electron beam tomography, multispiral computer tomography), magnetic resonance angiography, thallium stress scintigraphy, single photon positron emission tomography, dobutamine stress echocardiography, endovascular ultrasound study. Coronary angiography is the gold standard for diagnosis of congenital anomalies of coronary arteries. Drug therapy, transluminal balloon angioplasty with stenting or surgical revascularization are indicated to patients with overt clinical picture.

Topics: Adult; Angioplasty, Balloon, Coronary; Asymptomatic Diseases; Cardiomyopathies; Cardiovascular Agents; Coronary Angiography; Coronary Vessel Anomalies; Death, Sudden, Cardiac; Diagnosis, Differential; Echocardiography; Heart Failure; Humans; Magnetic Resonance Angiography; Male; Myocarditis; Tomography, Spiral Computed; Young Adult

Cardiotoxicity is a rare but serious complication of 5-fluorouracil therapy. Coronary vasospasm and, less frequently, acute myocarditis have been identified as underlying mechanisms. We report a case of severe toxicity in a relatively young and fit male patient being treated for metastatic colonic adenocarcinoma displaying characteristics that cannot be explained by either mechanism alone.

Topics: Adenocarcinoma; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Arrhythmias, Cardiac; Cardiomyopathy, Dilated; Cardiovascular Agents; Colonic Neoplasms; Coronary Vasospasm; Fluorouracil; Heart Diseases; Humans; Leucovorin; Liver Neoplasms; Male; Middle Aged; Myocarditis; Organoplatinum Compounds; Oxaliplatin; Treatment Outcome; Ventricular Dysfunction, Left

Topics: Aortic Valve Stenosis; Atrioventricular Block; Cardiac Surgical Procedures; Cardiovascular Agents; Diagnostic Imaging; Electrocardiography; Endocardial Fibroelastosis; Endocardium; Heart Failure; Humans; Infant; Infant, Newborn; Mumps; Myocarditis; Prognosis

Viral myocarditis is a frequent and often unrecognised cause of post-inflammatory cardiomyopathy. The role of viral persistence and heart-specific autoimmunity in the development of myocarditis and heart failure is still controversial. This review updates the current view on the immunological mechanisms of disease development and addresses the current and future role of immunomodulation and immunosuppression as treatment options for defined subgroups of patients with myocarditis or dilated cardiomyopathy.

Topics: Animals; Cardiovascular Agents; Clinical Trials as Topic; Humans; Immunologic Factors; Immunosuppressive Agents; Myocarditis; Virus Diseases

Myocarditis is a common inflammatory heart disease in children and young adults that may result in chronically dilated cardiomyopathy. Coxsackievirus B3 is the major etiologic agent of this disease. Current treatments for patients with viral myocarditis are almost entirely supportive. In recent years, some promising therapeutic candidates have emerged, including novel treatments and improvements of existing drugs. Among these are molecules that specially target virus entry, such as pleconaril, WIN 54954 and CAR-Fc; nucleic acid-based antiviral agents that inhibit viral translation and/or transcription, such as antisense oligodeoxynucleotide and short interfering RNA; and immunomodulatory agents that augment the host-protective immune responses to effectively clear viruses from target tissues, including interferons and immunoglobulins. In addition, certain new antiviral strategies, still in the early stages, include modulation of signal transduction pathways responsible for viral replication using enzyme inhibitors, which have revealed potential therapeutic targets for viral myocarditis. Finally, the progress in cellular cardiomyoplasty for end-stage therapy, in particular the preliminary clinical trials, is also discussed with respect to its potential future application.

Topics: Antiviral Agents; Cardiovascular Agents; Coxsackievirus Infections; Enterovirus; Humans; Myocarditis; Stem Cell Transplantation

Apoptosis continues to be a controversial concept and subject of debate among scientists regarding its value as the basis for new therapeutic strategies. Today, it is widely accepted that the death of cardiac myocytes under a variety of conditions appears to be apoptotic based on a variety of criteria. However, the significance of these observations and how the insights into apoptotic molecular pathways may provide novel therapeutic targets remains to be determined. It is important to reconsider the pertinent underlying mechanisms of apoptosis regulation, and how these molecular pathways may be viewed in the functioning, intact heart. This knowledge can be applied in pursuit of practical goals in a search for new ways to prevent myocardial damage following such injuries as ischaemia/reperfusion or exposure to cardiotoxic drugs. Although recent literature contains reports of positive findings, there has not yet been a rigorous application of the model of apoptosis in the myocardium, and the potential for development of new therapeutic strategies is not yet understood.

Topics: Animals; Apoptosis; Biological Evolution; Cardiovascular Agents; Cell Differentiation; Cysteine Proteinase Inhibitors; Drug Design; Endothelial Cells; Humans; Lysophospholipids; Myocardial Ischemia; Myocarditis; Myocardium; Myocytes, Cardiac; Necrosis; Rats; Signal Transduction

Topics: Biopsy; Cardiomyopathy, Dilated; Cardiovascular Agents; Humans; Myocarditis; Myocardium; Prognosis; Treatment Outcome

Topics: Anti-Inflammatory Agents; Biopsy; Cardiovascular Agents; Endocardium; Humans; Immunosuppressive Agents; Myocarditis; Myocardium; Prognosis

Carried out in this study for the first time was the diagnosis and treatment per groups of degree of severity of the clinical course of infectious myocarditis. According to the classification of the New York Association of Cardiology (1964, 1973), there has been established a clear correlation between the gravity of the process course, hemodialysis and cardiac haemodynamics.

Topics: Blood Coagulation; Cardiovascular Agents; Communicable Diseases; Disseminated Intravascular Coagulation; Drug Therapy, Combination; Hemodynamics; Humans; Lipid Peroxidation; Myocarditis

Topics: Adolescent; Cardiovascular Agents; Child; Child, Preschool; Diuretics; Heart Failure; Humans; Immunotherapy; Infant; Infant, Newborn; Myocarditis; Prognosis

Topics: Animals; Arachidonic Acids; Cardiovascular Agents; Coronary Disease; Free Radicals; Humans; Leukocytes; Lysosomes; Myocardial Infarction; Myocarditis; Necrosis; Oxygen Consumption; Phospholipids

In severe coronavirus disease (COVID)-19 patients, an extraordinary systemic inflammatory response is seen. It could impact in multiple organ disorders, specially a severe myocardial injury, an acute myocarditis results in focal or global myocardial inflammation and necrosis. Those events can be present in healthy subjects or cardiovascular (CV) patients. It is clinically associated with ventricular dysfunction exacerbation or worsening and tachyarrhythmias. It is also related to a poor outcome for CV patients with ischemic heart disease, hypertensión, and heart failure. COVID-19 patients require multiple and complex treatment that alleviates symptoms, the vast variety of agents interacts with diseases and CV drugs. Our purpose is to correlate in guidance synopsis: Adverse effects, pharmacological interactions, and CV drugs in COVID-19 treatment.. En pacientes con COVID-19 grave se ha observado una extraordinaria respuesta inflamatoria sistémica. Este impacto se traduce en múltiples trastornos de órganos, especialmente cardíacos, por lesión miocárdica grave, miocarditis aguda que resulta en inflamación focal o miocárdica global, necrosis cardiaca. Estos tremendos eventos son observados en sujetos sanos como pacientes cardiovasculares. Clínicamente asociados con nueva presentación o empeoramiento de la disfunción ventricular y taquiarritmias. Relacionado a un predictor principal de malos resultado en pacientes cardiovasculares (CV), especialmente en aquellos con cardiopatía isquémica, hipertensión e insuficiencia cardíaca. Los enfermos con COVID-19 requieren múltiples y complejos tratamientos que alivien los síntomas, esta gran variedad de agentes interactúa con enfermedades y medicamentos CV. Nuestro propósito es correlacionar, en una guía sinóptica: efectos adversos, interacciones farmacológicas y fármacos cardiovasculares en el tratamiento del COVID-19.

Topics: Cardiovascular Agents; Cardiovascular Diseases; COVID-19 Drug Treatment; Drug Interactions; Humans; Myocarditis

Obesity-induced cardiomyopathy involves chronic and sustained inflammation. The toll-like receptor 4 (TLR4) signaling pathway can associate innate immunity with obesity. Myeloid differentiation primary response 88 (MyD88), an indispensable downstream adaptor molecule of TLR4, has been reported to mediate obesity complications. However, whether inhibition of MyD88 can mitigate obesity-induced heart injury remains unclear. LM8, a new MyD88 inhibitor, exhibits prominent anti-inflammatory activity in lipopolysaccharide-treated macrophages. In this study, the protective effects of LM8 on a high-fat diet (HFD)-induced heart injury were assessed in a mouse model of obesity. As suggested from the achieved results, LM8 treatment alleviated HFD-induced pathological and functional damages of the heart in mice. Meantime, the treatment of mice with LM8 could significantly inhibit myocardial hypertrophy, fibrosis, inflammatory cytokines expression, and inflammatory cell infiltration induced by HFD. Besides, LM8 administration inhibited the formation of MyD88/TLR4 complex, phosphorylation of ERK, and activation of nuclear factor-κB induced by HFD. According to the achieved results, MyD88 inhibitor LM8 ameliorated obesity-induced heart injury by inhibiting MyD88-ERK/nuclear factor-κB dependent cardiac inflammatory pathways. Furthermore, targeting MyD88 might be a candidate of a therapeutic method to treat obesity-induced heart injury.

Topics: Animals; Cardiomegaly; Cardiomyopathies; Cardiovascular Agents; Cells, Cultured; Cytokines; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; Fibrosis; Male; Mice, Inbred C57BL; Myeloid Differentiation Factor 88; Myocarditis; Myocytes, Cardiac; NF-kappa B; Obesity; Signal Transduction; Toll-Like Receptor 4

Topics: Adult; Anti-Inflammatory Agents; Antineoplastic Combined Chemotherapy Protocols; Arsenic Trioxide; Cardiovascular Agents; Chest Pain; Drug Substitution; Echocardiography; Electrocardiography; Humans; Idarubicin; Leukemia, Promyelocytic, Acute; Male; Myocarditis; Pericarditis; Remission Induction; Tretinoin

There is controversy about the outcome of patients with acute myocarditis (AM), and data are lacking on how patients admitted with suspected AM are managed. We report characteristics, in-hospital management, and long-term outcome of patients with AM based on a retrospective multicenter registry from 19 Italian hospitals.. A total of 684 patients with suspected AM and recent onset of symptoms (<30 days) were screened between May 2001 and February 2017. Patients >70 years of age and those >50 years of age without coronary angiography were excluded. The final study population comprised 443 patients (median age, 34 years; 19.4% female) with AM diagnosed by either endomyocardial biopsy or increased troponin plus edema and late gadolinium enhancement at cardiac magnetic resonance.. At presentation, 118 patients (26.6%) had left ventricular ejection fraction <50%, sustained ventricular arrhythmias, or a low cardiac output syndrome, whereas 325 (73.4%) had no such complications. Endomyocardial biopsy was performed in 56 of 443 (12.6%), and a baseline cardiac magnetic resonance was performed in 415 of 443 (93.7%). Cardiac mortality plus heart transplantation rates at 1 and 5 years were 3.0% and 4.1%. Cardiac mortality plus heart transplantation rates were 11.3% and 14.7% in patients with complicated presentation and 0% in uncomplicated cases (log-rank P<0.0001). Major AM-related cardiac events after the acute phase (postdischarge death and heart transplantation, sustained ventricular arrhythmias treated with electric shock or ablation, symptomatic heart failure needing device implantation) occurred in 2.8% at the 5-year follow-up, with a higher incidence in patients with complicated forms (10.8% versus 0% in uncomplicated AM; log-rank P<0.0001). β-Adrenoceptor blockers were the most frequently used medications both in complicated (61.9%) and in uncomplicated forms (53.8%; P=0.18). After a median time of 196 days, 200 patients had follow-up cardiac magnetic resonance, and 8 of 55 (14.5%) with complications at presentation had left ventricular ejection fraction <50% compared with 1 of 145 (0.7%) of those with uncomplicated presentation.. In this contemporary study, overall serious adverse events after AM were lower than previously reported. However, patients with left ventricular ejection fraction <50%, ventricular arrhythmias, or low cardiac output syndrome at presentation were at higher risk compared with uncomplicated cases that had a benign prognosis and low risk of subsequent left ventricular systolic dysfunction.

Topics: Acute Disease; Adolescent; Adult; Aged; Biomarkers; Biopsy; Cardiovascular Agents; Female; Heart Transplantation; Hospital Mortality; Hospitalization; Humans; Italy; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Registries; Retrospective Studies; Risk Factors; Stroke Volume; Time Factors; Treatment Outcome; Troponin; Ventricular Function, Left; Young Adult

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

Alpha-1-antitrypsin (AAT) is an abundant plasma protein with neutrophil elastase-inhibiting activity, and AAT is available as a plasma-derived therapeutic (pAAT). In experimental myocardial infarction, pAAT reduced acute inflammatory injury because of ischemia-reperfusion. The aim of the present study was to assess the properties of a recombinant protein composed of human AAT fused to the human immunoglobulin (Ig) G1 Fc fragment (rhAAT-Fc) in experimental myocardial infarction.. Ten-week-old CD1 male mice underwent transient occlusion (30 minutes) of the left anterior coronary artery. rhAAT-Fc (2 mg/kg) or pAAT (60 mg/kg) were administered upon reperfusion. We used human plasma-derived Ig (2 mg/kg) or a matching volume of NaCl 0.9% as control solutions. After 24 hours, infarct size and caspase-1 activity were quantified. The left ventricular ejection fraction (LVEF) was measured by echocardiography at 24 hours and 7 days. A variant of rhAAT-Fc lacking elastase inhibition activity, rhAAT-Fc, was also tested.. The rhAAT-Fc induced a significant reduction in infarct size (P < 0.01 vs. all controls, P > 0.05 vs. pAAT). Caspase-1 activity was reduced to the same degree with rhAAT-Fc and pAAT (-70%; P < 0.05; P > 0.05 rhAAT-Fc vs. pAAT). The effects on infarct size after a single administration were reflected by preservation of LVEF at 24 hours and 7 days (all P < 0.05). rhAAT-Fc without elastase inhibiting activity, rhAAT-Fc, conferred comparable effects on infarct size, caspase-1 activity, and LVEF (P > 0.2 vs. rhAAT-Fc).. The pAAT and recombinant human AAT-Fc reduce the acute myocardial inflammatory injury after ischemia-reperfusion in the mouse leading to preservation of viable myocardium and systolic function, independent on the effects on neutrophil elastase.

Topics: alpha 1-Antitrypsin; Animals; Cardiovascular Agents; Caspase 1; Disease Models, Animal; Humans; Immunoglobulin Fc Fragments; Leukocyte Elastase; Male; Mice; Myocardial Infarction; Myocardial Reperfusion Injury; Myocarditis; Myocardium; Recombinant Fusion Proteins; Stroke Volume; Time Factors; Tissue Survival; Ventricular Function, Left

Topics: Adenoviridae Infections; Adult; Biopsy; Cardiovascular Agents; Combined Modality Therapy; Defibrillators; Disease Progression; Emergencies; Female; Fever; Heart-Assist Devices; Hemodynamics; Humans; Myocarditis; Myocardium; Parvoviridae Infections; Pericarditis; Shock, Cardiogenic; Spironolactone; Ventricular Dysfunction, Left

Myocarditis is considered one of the major causes of dilated cardiomyopathy. Hepatocyte growth factor (HGF) has pleiotropic activities that promote tissue regeneration and facilitate functional improvement of injured tissue. We investigated whether the epicardial sustained-release of HGF, using gelatin hydrogel sheets, improves cardiac function in a chronic myocarditis rat model.. Six weeks after Lewis rats were immunized with porcine cardiac myosin to establish autoimmune myocarditis, HGF- or normal saline (NS)-incorporated gelatin hydrogel sheets were applied to the epicardium (G-HGF and G-NS, respectively). At either 2 or 4 weeks after treatment, these were compared with the Control myocarditis group. Cardiac function was evaluated by echocardiography and cardiac catheterization. Development of fibrosis was determined by histological study and expression of transforming growth factor-β1 (TGF-β1). Bax and Bcl-2 levels were measured to evaluate apoptotic activity.. At both points, fractional shortening and end-systolic elastance were higher in the G-HGF group than in the Control and G-NS groups (P < 0.01). Fractional shortening at 2 weeks of each group were as follows: 31.0 ± 0.9%, 24.8 ± 2.7% and 48.6 ± 2.6% (Control, G-NS and G-HGF, respectively). The ratio of the fibrotic area of the myocardium was lower in the G-HGF group than in the Control and G-NS groups at 2 weeks (G-HGF, 8.8 ± 0.9%; Control, 17.5 ± 0.2%; G-NS, 15.6 ± 0.7%; P < 0.01). The ratio at 4 weeks was lower in the G-HGF group than in the G-NS group (10.9 ± 1.4% vs 18.5 ± 1.3%; P < 0.01). The mRNA expression of TGF-β1 in the G-HGF group was lower than in the Control group at 2 weeks (0.6 ± 0.1 vs 1.1 ± 0.2) and lower than that in the G-NS group at 4 weeks (0.7 ± 0.1 vs 1.3 ± 0.2). The Bax-to-Bcl-2 ratios at both points were lower in the G-HGF group than in the Control group.. Sustained-released HGF markedly improves cardiac function in chronic myocarditis rats. The antifibrotic and antiapoptotic actions of HGF may contribute to the improvement. HGF-incorporated gelatin hydrogel sheet can be a new therapeutic modality for myocarditis.

Topics: Animals; Apoptosis; Autoimmune Diseases; bcl-2-Associated X Protein; Cardiac Myosins; Cardiovascular Agents; Chemistry, Pharmaceutical; Chronic Disease; Delayed-Action Preparations; Disease Models, Animal; Drug Carriers; Fibrosis; Gelatin; Gene Expression Regulation; Hepatocyte Growth Factor; Hydrogels; Immunization; Male; Myocardial Contraction; Myocarditis; Myocardium; Rats; RNA, Messenger; Swine; Time Factors; Transforming Growth Factor beta1; Ventricular Function, Left

There is a lack of clear diagnostic and management guidelines for acute myocarditis in the pediatric population. We used a multi-institutional database to characterize demographics, practice variability, and outcomes in this population.. Patients with acute myocarditis (n=514) were identified from April 2006 to March 2011 using the Pediatric Health Information System database, and regional variations in management and outcomes were analyzed. Ninety-seven patients (18.9%) received extracorporeal membrane oxygenation, 22 (4.3%) received ventricular assist device, 21 (4.1%) received heart transplantation, and 37 (7.2%) died. Of the 104 patients who received extracorporeal membrane oxygenation or ventricular assist device, 17 (16.3%) had heart transplantation, 25 (24%) died, and 62 (59.6%) showed recovery of myocardial function. There was a decrease in the use of endomyocardial biopsy (P=0.03) and an increase in the use of magnetic resonance imaging (P<0.01) over the study period. Although the use of medications and procedures varied between different regions, the occurrence of death or heart transplantation showed no significant regional associations. The use of extracorporeal membrane oxygenation (odds ratio, 5.8; 95% confidence interval, 2.9-11.4; P<0.01), ventricular assist device (odds ratio, 8.2; 95% confidence interval, 2.7-24.9; P<0.01), and vasoactive medications (odds ratio, 5.7; 95% confidence interval, 1.2-26.1; P=0.03) was independently associated with death/transplantation.. There is significant temporal and regional variation in the diagnostic modalities and management used for pediatric myocarditis, which continues to have high morbidity and mortality. Extracorporeal membrane oxygenation, ventricular assist device, and vasoactive medications are independently associated with increased mortality/transplantation.

Topics: Acute Disease; Adolescent; Age Distribution; Age Factors; Biopsy; Cardiovascular Agents; Chi-Square Distribution; Child; Child, Preschool; Extracorporeal Membrane Oxygenation; Female; Healthcare Disparities; Heart Transplantation; Heart-Assist Devices; Humans; Infant; Linear Models; Logistic Models; Magnetic Resonance Imaging; Male; Multivariate Analysis; Myocarditis; Odds Ratio; Practice Patterns, Physicians'; Predictive Value of Tests; Recovery of Function; Residence Characteristics; Retrospective Studies; Risk Assessment; Risk Factors; Survival Analysis; Time Factors; Treatment Outcome; United States; Young Adult

Cardiomyopathy refers to nonspecific myocardial dysfunction that may be due to a variety of causes. Viral illnesses have long been known to cause cardiomyopathy, and the list of viral causes is extensive. Influenza infection is a rare cause of myocarditis. Recent reports, however, indicate that influenza A (H1N1) can cause acute myocarditis and cardiomyopathy in adults and fulminant myocarditis in children as seen during the 2009 global outbreak of the H1N1 influenza virus. The following presents a case series of adult patients with acute reversible cardiomyopathy associated with influenza A (H1N1) infection (see Table 1 for patient characteristics).

Topics: Acute Disease; Aged; Antiviral Agents; Cardiomyopathies; Cardiovascular Agents; Female; Humans; Influenza A Virus, H1N1 Subtype; Influenza, Human; Male; Middle Aged; Myocarditis; Recovery of Function; Treatment Outcome; Ultrasonography; Ventricular Dysfunction, Left; Ventricular Function, Left

Noncompaction myocardium (NCM) is a genetic heterogeneous primary cardiomyopathy which affects both children and adults and can be either isolated or combined with other congenital heart disorders. It has common pathogenesis of symptoms but is distinguished by pronounced clinical polymorphism. We have observed 25 adult patients (15 men, 10 women aged from 20 to 62 years, mean age 42.9+/-13.3 years) with NCM syndrome. Heart failure have been found in 96% of patients (functional class [FC] I in 7, II - in 6, III in 7, and IV - in 4 patients). Ninety two percent of patients have ventricular extrasystoles, 32% - atrial fibrillation, 28% - FC I-III angina. Mean end diastolic left ventricular dimension is 6.5+/-0.8cm, ejection fraction 29.7+/-13.0%, mean pulmonary artery pressure - 42.6+/-13.5 mm Hg. Intracardiac thrombosis have been found in 24% of patients. In 7 patients morphological study of myocardium has been performed. NCM syndrome was diagnosed at initial investigation just in 1 case. We distinguished the following clinical masks (variants of diagnosis) of NCM: 1) clinically not manifest, is revealed at accidental examination (4%); 2) exists under mask of "idiopathic" rhythm disturbances (8%); 3) has a mask of ischemic heart disease; 4) is revealed in patients with acute or subacute myocarditis (12%); 5) has a mask of dilated cardiomyopathy (52%); 6) NCM in patients with other primary cardiomyopathies (hypertrophic, restrictive, genetic myopathy, arrhythmogenic right ventricular dysplasia). Combination of NCM with congenital heart defects has been found in 20% of patients. In 56% of cases myocarditis was diagnosed (it was viral in no less than 44%). Only in 32% of patients it is possible to consider presence of isolated NCM syndrome. This paper contains discussion of problems of diagnostics (including morphological) and treatment in the presented group of patients, significance of myocarditis for development of decompensation, role of NCM in patients with other primary cardiomyopathies, possibility of compensatory (secondary) character of NCM in severe systolic dysfunction.

Topics: Adult; Arrhythmias, Cardiac; Biopsy; Cardiomyopathies; Cardiovascular Agents; Diagnosis, Differential; Disease Management; Electrocardiography; Female; Heart Defects, Congenital; Heart Failure; Heart Function Tests; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Myocarditis; Myocardium; Prognosis; Syndrome; Tomography, Spiral Computed; Treatment Outcome

Regardless of the origin, injury to the heart can result in cardiomyocyte hypertrophy, fibrosis, and cell death. Myocarditis often progresses to dilated cardiomyopathy (DCM), a major cause of heart failure. In our study, we used a rat model of myosin-induced experimental autoimmune myocarditis (EAM), in which the heart transits from an acute phase (inflammatory myocarditis) to a chronic phase (remodeling and DCM). Our objective was to investigate whether T-3999, a novel phenylpyridazinone, can reduce this progression. Four weeks after myosin injection, T-3999 was administered daily to male Lewis rats in two doses (3 and 10 mg/kg, orally). Four weeks later, treatment was terminated; hemodynamic and echocardiographic measurements were performed; hearts were excised for histopathology and estimation of histamine, mRNA, and protein levels. Mortality rate was reduced by drug treatment. T-3999 reduced % fibrosis and tissue collagen III. Profibrotic markers-transforming growth factor-β(1), tumor necrosis factor-α, and galectin-3--were attenuated by treatment. Mast cell density and degranulation, and tissue histamine concentration were also reduced. This indicates an anti-inflammatory effect of the drug in reducing fibrosis. Hypertrophy was reduced as reflected by reduced myocyte diameter and natriuretic peptide expression. T-3999 treatment increased the sarcoendoplasmic reticulum Ca(2+) ATPase 2 protein level and improved several cardiac function parameters. The reduction of the remodeling process and improvement in myocardial function suggest an effect of T-3999 in attenuating ventricular remodeling in post-myocarditis DCM.

Topics: Animals; Autoimmune Diseases; Cardiomyopathy, Dilated; Cardiovascular Agents; Cell Degranulation; Cytokines; Disease Models, Animal; Disease Progression; Fibrosis; Hemodynamics; Histamine Release; Male; Mast Cells; Myocarditis; Myosins; Pyridazines; Rats; Rats, Inbred Lew; Time Factors; Ultrasonography; Ventricular Remodeling

Organic cation transporters (OCT1-3 and OCTN1/2) facilitate cardiac uptake of endogenous compounds and numerous drugs. Genetic variants of OCTN2, for example, reduce uptake of carnitine, leading to heart failure. Whether expression and function of OCTs and OCTNs are altered by disease has not been explored in detail. We therefore studied cardiac expression, heart failure-dependent regulation, and affinity to cardiovascular drugs of these transporters. Cardiac transporter mRNA levels were OCTN2>OCT3>OCTN1>OCT1 (OCT2 was not detected). Proteins were localized in vascular structures (OCT3/OCTN2/OCTN1) and cardiomyocytes (OCT1/OCTN1). Functional studies revealed a specific drug-interaction profile with pronounced inhibition of OCT1 function, for example, carvedilol [half maximal inhibitory concentration (IC₅₀), 1.4 μmol/L], diltiazem (IC₅₀, 1.7 μmol/L), or propafenone (IC₅₀, 1.0 μmol/L). With use of the cardiomyopathy model of coxsackievirus-infected mice, Octn2mRNA expression was significantly reduced (56% of controls, 8 days after infection). Accordingly, in endomyocardial biopsy specimens OCTN2 expression was significantly reduced in patients with dilated cardiomyopathy, whereas the expression of OCT1-3 and OCTN1 was not affected. For OCTN2 we observed a significant correlation between expression and left ventricular ejection fraction (r = 0.53, P < 0.0001) and the presence of cardiac CD3⁺ T cells (r = -0.45, P < 0.05), respectively. OCT1, OCT3, OCTN1, and OCTN2 are expressed in the human heart and interact with cardiovascular drugs. OCTN2 expression is selectively reduced in dilated cardiomyopathy patients and predicts the impairment of cardiac function.

Topics: Adult; Aged; Animals; Biopsy; Cardiomyopathy, Dilated; Cardiovascular Agents; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Male; Mice; Middle Aged; Myocarditis; Myocardium; Organic Cation Transport Proteins; RNA, Messenger

Topics: Adult; Antigens, Viral; Capsid; Cardiopulmonary Resuscitation; Cardiovascular Agents; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Electrocardiography; Epstein-Barr Virus Infections; Female; Herpesvirus 4, Human; Humans; Immunoglobulin G; Immunoglobulin M; Myocarditis; Shock, Cardiogenic; Ventricular Fibrillation

We report the case of a 22-year-old man who developed severe myocarditis following a presumed katipo spider bite. Katipo spiders are thought to be one of the most poisonous native creatures in New Zealand. No deaths from katipo spider bites have been reported since the 19th Century. A literature search reveals no previously reported cases of myocarditis following a bite from a katipo spider. The clinical presentation of latrodectism is discussed.

Topics: Animals; Cardiovascular Agents; Coronary Angiography; Diagnosis, Differential; Echocardiography; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Myocarditis; Spider Bites; Spiders; Young Adult

A 60-year-old man who had serious chest and arm pain died suddenly during hospitalization. He suffered from coronary vasospastic angina complicated by a fatal acute fulminant-type of myocarditis associated with Churg-Strauss syndrome (CSS). The diagnosis at autopsy was acute progressive eosinophilic myocarditis associated with CSS.

Topics: Angina Pectoris; Autopsy; Cardiovascular Agents; Churg-Strauss Syndrome; Coronary Angiography; Coronary Vasospasm; Death, Sudden, Cardiac; Electrocardiography; Eosinophilia; Fatal Outcome; Humans; Male; Middle Aged; Myocarditis

Acute myocarditis is one of the most challenging diagnoses in cardiology. It is a disease with variable clinical presentation, progression and outcome.. To assess clinical characteristics and outcome of patients hospitalised with diagnosis of acute myocarditis from year 2006 to 2008.. We analysed hospital files of consecutive 32 patients admitted to our hospital due to myocarditis. All demographic, clinical and laboratory data were analysed and compared between patients with acute or subacute myocarditis. After discharge the patients were followed for 8-24 months.. The majority of patients were males (84%) in a mean age of 33 years. Clinical and echocardiographic parameters improved in 25 (78%) of patients during hospital stay. During follow-up decreased left ventricular ejection fraction (LVEF) was observed more often in patients with subacute than acute myocarditis (mean LVEF values of 49 vs. 61%, respectively). Patients with a subacute form of the disease more frequently required chronic pharmacological therapy and more often retired from occupational activities.. Diagnosis of myocarditis is still challenging. Careful history taking, serial laboratory, ECG and echocardiographic examinations are helpful in therapeutic decisions making and assessing prognosis. Patient with subacute myocarditis are more symptomatic than patients with acute myocarditis.

Topics: Adult; Cardiovascular Agents; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Humans; Length of Stay; Male; Myocarditis; Retrospective Studies; Stroke Volume; Treatment Outcome

Topics: Adult; Cardiology; Cardiovascular Agents; Electrocardiography; Female; Follow-Up Studies; Humans; Length of Stay; Male; Myocarditis; Treatment Outcome

Topics: Adult; Angina Pectoris; Anticoagulants; Biopsy; Cardiovascular Agents; Endocardium; Heart Diseases; Heart Failure; Humans; Magnetic Resonance Imaging; Male; Myocarditis; Parvoviridae Infections; Parvovirus B19, Human; Thrombosis

Topics: Acute Disease; Adjuvants, Immunologic; Autoantibodies; Autoantigens; Autoimmune Diseases; B-Lymphocytes; Cardiovascular Agents; Chronic Disease; DNA; Humans; Immunoglobulin G; Immunoglobulin M; Immunosuppressive Agents; Methylhydrazines; Myocarditis; Myocardium; Recurrence; T-Lymphocytes; Virus Diseases

In a retrospective study 159 cases (1.8%) of myocarditis--7 pediatric--were found among 8663 consecutive autopsies. In 5 cases the diagnosis had been suspected clinically. In 68 cases (42%) it was possible to determine the etiology: 61 cases of septic myocarditis were found, including 4 mycotic, and 4 cases of toxoplasmosis. In 91 cases (58%) the myocarditis was idiopathic. Idiopathic myocarditis was firmly established as cause of death in 10 cases. In the other cases there appeared to be a relation between the extent of the myocardial infiltrate and probable involvement of the process as cause of death.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Autopsy; Cardiovascular Agents; Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Male; Middle Aged; Myocarditis; Myocardium; Retrospective Studies

Topics: Autoimmune Diseases; Cardiovascular Agents; Humans; Hypersensitivity; Myocarditis

Topics: Adams-Stokes Syndrome; Adrenal Cortex Hormones; Cardiovascular Agents; Female; Heart; Heart Block; Humans; Myocarditis

Topics: Animals; Cardiovascular Agents; Electrocardiography; Ergot Alkaloids; Ergotamine; Humans; Lagomorpha; Myocarditis; Oxytocics; Rabbits