natriuretic-peptide--brain and Cardiomyopathy--Hypertrophic

Hypertrophic cardiomyopathy (HCM) is a common known monogenetic cardiovascular disorder which frequently leads to symptoms such as dyspnea and exercise intolerance. Current guideline-recommended pharmacotherapies have variable therapeutic responses. Mavacamten, a small molecule modulator of β-cardiac myosin, reduces hypercontractility, a central mechanism in the pathogenesis of HCM. Mavacamten has recently been evaluated in Phase 2 and 3 clinic trials for obstructive and nonobstructive symptomatic HCM.. This article reviews available preclinical and clinical trials assessing the efficacy and safety of Mavacamten for the treatment of symptomatic obstructive and nonobstructive HCM.. Findings from Phase 2 and 3 trials suggest that Mavacamten represents a very promising new therapy for the treatment of symptomatic patients with HCM. Treatment leads to an improvement in symptomatic and physiologic metrics for symptomatic patients with HCM with minimal adverse events. Patients with obstructive HCM demonstrated a significant improvement in LVOT gradient, NYHA functional class, Kansas City Cardiomyopathy Questionnaire (KCCQ), Overall Summary Score (OSS), and numerical rating scale (NRS) dyspnea scores; and patients with both obstructive and nonobstructive HCM had significant improvement in serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations.

Topics: Animals; Benzylamines; Cardiomyopathy, Hypertrophic; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Uracil; Ventricular Myosins

Approximately 50% of patients with symptoms and signs of heart failure have a left ventricular ejection fraction (LVEF) ≥50% and are often simply referred to as 'heart failure with preserved EF', 'HFpEF'. Many of such patients have HF secondary to specific cardiac conditions (i.e., valvular or pericardial disease) in which the symptoms and signs occur despite the LVEF being preserved due to diastolic dysfunction secondary to the underlying disease (secondary HFpEF), differently from those HFpEF patients in which the impaired LV filling is due to a primary diastolic dysfunction (primary HFpEF). When primary HFpEF patients are properly diagnosed, they appear to have a milder form of HF with a lower cardiovascular mortality compared with HFrEF and secondary HFpEF population, but a risk of HF hospitalization that is significantly higher than patients with similar cardiovascular risk factors but without the diagnosis of HFpEF. We herein review the diagnostic approach to HFpEF and present a differential diagnosis of HFpEF in a primary and secondary form.

Topics: Algorithms; Biomarkers; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiomyopathy, Restrictive; Heart Failure, Diastolic; Heart Valve Diseases; Humans; Natriuretic Peptide, Brain; Obesity; Peptide Fragments; Pericarditis, Constrictive; Risk Factors; Stroke Volume; Tachycardia

Cardiac amyloidosis is a rare, infiltrative cardiomyopathy that presents with thickened ventricular walls and progressive heart failure. The morphological findings and clinical features are shared with many other diseases (i.e. hypertrophic cardiomyopathy, 'athlete's heart,' Fabry disease, and hypertensive cardiomyopathy), and misdiagnosis occurs frequently. Cardiologists have many instruments that can help reach a correct diagnosis in a relatively short time. As tiles of a mosaic are placed to create an image, thoughtful and smart use of the different diagnostic tools available allows the opportunity to identify amyloid infiltration of the myocardium. When the myocardium is involved, prognosis is poor, so identification of its involvement is crucial for disease management. The diagnostic process begins with an accurate evaluation of clinical elements and includes cardiovascular imaging (echocardiography, magnetic resonance, and nuclear medicine), electrocardiography, serological assays, and myocardial biopsy; only the appropriate integration of these instruments can reveal the diagnosis to an expert physician. The latest improvements in non-invasive diagnostic techniques with increased diagnostic power have reduced the need for biopsy.

Topics: Amyloidosis; Biomarkers; Biopsy; Cardiomyopathy, Hypertrophic; Diagnosis, Differential; Echocardiography; Electrocardiography; Humans; Magnetic Resonance Imaging, Cine; Myocardium; Natriuretic Peptide, Brain; Predictive Value of Tests; Radionuclide Imaging; Radiopharmaceuticals; Sensitivity and Specificity; Severity of Illness Index

This report describes a transient hypertrophic cardiomyopathy with right-ventricle outlet tract obstruction (RVOTO) induced by perinatal stress due to a major surgical procedure in a female newborn with congenital abnormalities. On day 10, she presented with heart failure, abnormal B-type natriuretic peptide (BNP), and an echocardiogram showing normal wall thickness. An in-hospital follow-up echocardiogram showed biventricular hypertrophy and RVOTO. At discharge, the infant was asymptomatic, with a normal echocardiogram and BNP. Transient RVOTO triggered by surgical stress and abnormal BNP have not been reported previously. Pathophysiology, the role of BNP, and clinical characteristics are discussed.

Topics: Abnormalities, Multiple; Apgar Score; Biomarkers; Cardiomyopathy, Hypertrophic; Cesarean Section; Combined Modality Therapy; Echocardiography, Doppler; Electrocardiography; Female; Follow-Up Studies; Humans; Hydrocephalus; Infant, Newborn; Meningomyelocele; Natriuretic Peptide, Brain; Risk Assessment; Spinal Dysraphism; Takotsubo Cardiomyopathy; Treatment Outcome; Ultrasonography, Prenatal; Ventricular Outflow Obstruction

Topics: Angiotensin II; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Biomarkers; Calcium Channel Blockers; Cardiomyopathy, Hypertrophic; Disease Models, Animal; Humans; Natriuretic Peptide, Brain

Topics: Animals; Atrial Natriuretic Factor; Biopsy; Cardiomyopathy, Hypertrophic; Cricetinae; Endocardium; Gene Expression; Humans; Immunohistochemistry; Mesocricetus; Microscopy, Electron; Myocardium; Natriuretic Peptide, Brain; Natriuretic Peptide, C-Type; Rats; Rats, Inbred SHR; RNA, Messenger; Swine

Topics: Adult; Aging; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Child; Heart Failure; Humans; Myocardial Infarction; Natriuretic Peptide, Brain; Nerve Tissue Proteins

The aim of this study was to investigate what factor determines tachycardia-induced secretion of atrial and brain natriuretic peptides (ANP and BNP, respectively) in patients with hypertrophic cardiomyopathy (HCM). HCM patients with normal left ventricular (LV) systolic function and intact coronary artery (n = 22) underwent rapid atrial pacing test. The cardiac secretion of ANP and BNP and the lactate extraction ratio (LER) were evaluated by using blood samples from the coronary sinus and aorta. LV end-diastolic pressure (LVEDP) and the time constant of LV relaxation of tau were measured by a catheter-tip transducer. These parameters were compared with normal controls (n = 8). HCM patients were divided into obstructive (HOCM) and nonobstructive (HNCM) groups. The cardiac secretion of ANP was significantly increased by rapid pacing in HOCM from 384 +/- 101 to 1,268 +/- 334 pg/ml (P < 0.05); however, it was not significant in control and HNCM groups. In contrast, the cardiac secretion of BNP was fairly constant and rather significantly decreased in HCM (P < 0.01). The cardiac ANP secretion was significantly correlated with changes in LER (r = -0.57, P < 0.01) and tau (r = 0.73, P < 0.001) in HCM patients. Tachycardia potentiates the cardiac secretion of ANP, not BNP, in patients with HCM, particularly when it induces myocardial ischemia and LV diastolic dysfunction.

Topics: Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Tachycardia; Ventricular Dysfunction, Left

We investigated the relation between left ventricular structure and the secretion patterns of A- and B-type natriuretic peptides (ANP and BNP) by comparing their plasma levels in patients with hypertrophic cardiomyopathy (HC) and patients with idiopathic dilated cardiomyopathy (IDC). The secretion of ANP and BNP was much higher in patients with HC than in those with IDC; this shows that left ventricular cavity size is a key factor that regulates the secretion of ANP and BNP.

Topics: Aged; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Female; Humans; Linear Models; Male; Middle Aged; Natriuretic Peptide, Brain; Probability; Prognosis; Reference Values; Sensitivity and Specificity; Severity of Illness Index; Stroke Volume

Topics: Cardiomyopathy, Hypertrophic; Humans; Natriuretic Peptide, Brain; Peptide Fragments

In this study, our aim was to investigate the role of cardiac biomarkers in predicting the presence of significant coronary artery disease in hypertrophic cardiomyopathy (HCM) patients.. The study population was composed of hypertrophic cardiomyopathy patients who underwent coronary angiography at a single center between June 2021 and March 2023, and whose cardiac biomarkers were evaluated before the procedure. HCM patients were screened retrospectively. Significant CAD was defined as > 50% stenosis of the left main coronary artery or > 70% stenosis in a major coronary vessel. Demographic, echocardiographic and cardiac biomarker values were compared between the two groups.. A total of 123 patients were evaluated. Significant CAD was detected in 39 (31.7%) patients. Patients with significant CAD had higher CK-MB values than those without CAD [2.8 (2.1-4.0) vs. 3.4 (2.8-4.6), p = 0.036], and a higher level of high-sensitivity troponin T (hs-TnT) than those without CAD (24 vs. 17.8, p = 0.022). the NT-proBNP/hs-TnT ratio was found to be significantly lower in patients with CAD than in those with CAD (31.4 vs. 21.4, p = 0.019). In multivariate anaylsis, NT-proBNP/hs-TnT was determined as an independent predictor for significant CAD. In ROC analysis, NT-proBNP/hs-TnT ratio lower than the cut-off value of 30.7 could detect the presence of significant CAD with 76.9% sensitivity and 53.6% specificity (AUC: 0.632, 95% CI: 0.528-0.736, p = 0.019).. To sum up, we suggest that cardiac biomarkers were valuable and simple parameters in terms of significant CAD in HCM patients.

Topics: Biomarkers; Cardiomyopathy, Hypertrophic; Constriction, Pathologic; Coronary Artery Disease; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Troponin T

Although numerous studies have suggested that elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) is positively correlated with cardiovascular events, especially the heart failure and heart failure-related death (HFRD), evidence of the association between NT-proBNP and the adverse outcomes of hypertrophic cardiomyopathy (HCM) is still relatively limited. The present study was performed to evaluate the relationship between NT-proBNP and outcomes in patients with HCM.. Observational cohort methodology was used in the present study, and a total of 227 patients were included. And the patients were followed for 44.97 ± 16.37 months. Patients were categorized into three groups according to these NT-proBNP tertiles: first tertile (≤910 pg/ml, n=68), second tertile (913-2141 pg/ml, n=68), and third tertile (≥2151 pg/ml, n=69). The adverse outcomes of the present study were all-cause death (ACD) and cardiac death (CD).. According to the risk category of NT-proBNP, the incidence of ACD (P=0.005) and CD (P=0.032) among the three groups showed significant differences. Multivariate Cox regression analysis suggested that the ACD and CD in the third tertile have 7.022 folds (hazard risk [HR] = 7.022 [95% confidence interval [CI]: 1.397-35.282], P=0.018) and 7.129 folds (HR = 7.129 [95% CI: 1.329-38.237], P=0.022) increased risks as compared with those in the first tertile. Kaplan-Meier survival analyses showed that the cumulative risks of ACD and CD in patients with HCM tended to increase.. The present study indicated NT-proBNP was a novel biomarker suitable for predicting adverse prognosis in patients with HCM, which may be used for early recognition and risk stratification.

Topics: Adult; Aged; Asian People; Biomarkers; Cardiomyopathy, Hypertrophic; Cause of Death; China; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Time Factors

Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.. The study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell's C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson's staining was analysed.. During follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson's trichrome staining in the myocardium (r=0.198, p<0.05).. NT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

Topics: Beijing; Biomarkers; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Incidence; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Protein Precursors; Risk Factors; Survival Rate; Time Factors

To explore the short-term changes after percutaneous intramyocardial septal radiofrequency ablation (PIMSRA) in patients with hypertrophic obstructive cardiomyopathy (HOCM), using quantitative analysis of two-dimensional speckle tracking imaging (2D-STI).. This prospective self-controlled study included 30 HOCM patients treated with PIMSRA. The study for each patient spanned over at least 1 year. Interventricular septal thickness and the left ventricular outflow tract peak pressure gradient (LVOT-PG) were measured through echocardiography, and 2D-STI was used to evaluate the left ventricular (LV) systolic function and synchrony. Cardiac function was assessed using the New York Heart Association's (NYHA) functional classification for cardiac disease, and through the serum levels of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Biomarkers procollagen type I carboxy-terminal propeptide (PICP) and matrix metalloproteinases-2 (MMP-2) were detected for noninvasive assessment of myocardial fibrosis.. The patients' interventricular septal thickness, LVOT-PG, NYHA class, and plasma PICP and MMP-2 levels at the first month postoperatively were significantly lower than before operation (all P < .05). The 2D-STI quantitative variables of LV systolic function and synchrony improved significantly (all P < .05). They improved further 1 year postoperatively (P < .01 or P < .001). Serum cTnI and NT-proBNP levels increased 1 month postoperatively, but significantly decreased 1 year postoperatively (both P < .05). Pearson or Spearman correlation analysis showed that the improvement of interventricular septal thickness, LVOT-PG, NYHA class, and the levels of cTnI, NT-proBNP, PICP and MMP-2, were in positive correlation with the restoration of LV systolic function and synchrony (P < .01 or P < .001).. The changes in 2D-STI quantitative variables related to LV systolic function and synchrony are closely correlated with the improvement of cardiac function in HOCM patients after PIMSRA. These 2D-STI variables can serve for objective, accurate, and noninvasive evaluation of the HOCM treatment.

Topics: Cardiomyopathy, Hypertrophic; Echocardiography; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radiofrequency Ablation; Systole; Treatment Outcome; Troponin T; Ventricular Function, Left

CMR feature tracking strain (CMR-FT) provides prognostic information. However, there is a paucity of data in hypertrophic cardiomyopathy (HCM). We sought to analyze global CMR-FT parameters in all four cardiac chambers and to assess associations with NT-proBNP and cardiac troponin T (hsTnT) in patients with HCM.. This retrospective study included 144 HCM patients and 16 healthy controls with CMR at 1.5 T. Analyses were performed on standard steady-state free precession cine (SSFP) CMR data using a commercially available software. Global left ventricular (LV) strain was assessed as longitudinal (LV. CMR-FT reveals LV and LA dysfunction in HCM despite normal LVEF. The association between impaired LV strain and elevated NT-proBNP and hsTnT indicates a link between unapparent functional abnormalities and disease severity in HCM. Typical CMR-FT findings in patients with hypertrophic cardiomyopathy.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Female; Follow-Up Studies; Heart Ventricles; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Retrospective Studies; ROC Curve; Stroke Volume; Ventricular Function, Left

Since the first report of an association between cardiac troponin (cTn) and adverse outcome in hypertrophic cardiomyopathy (HD), there is a paucity in confirmative data. We performed a prospective, prespecified 5-year follow-up cohort study of 135 HC patients who participated in a national multicenter project and underwent clinical evaluation, MRI (cine, LGE and T2-weighted imaging) and biomarker assessment (high-sensitivity cTnT (hs-cTnT), N-terminal pro-B-type natriuretic peptide, soluble tumorgenicity suppressor-2, Galectin-3, Growth differentiation factor-15, C-terminal Propeptide of Type I Collagen (CICP)). An elevated hs-cTnT concentration was defined as ≥14ng/L. Follow-up was systematically performed for the primary endpoint: a composite of sudden cardiac death, heart failure related death, stroke-related death, heart failure hospitalization, hospitalization for stroke, spontaneous sustained ventricular tachycardia (VT) or appropriate ICD discharge, and progression to NYHA class III-IV. Elevated hs-cTnT was present in 33 of 135 (24%) HC patients. During a median follow-up of 5.0 years (IQR: 4.9-5.1) 18 patients reached the primary endpoint. Using Cox regression analysis, elevated hs-cTnT was univariately associated with the primary endpoint (HR: 3.4 (95%CI: 1.4-8.7, p=0.009). Also female sex, previous syncope, previous non-sustained VT, reduced LV ejection fraction (<50%) and CICP were associated with the primary endpoint. In multivariable analysis, elevated hs-cTnT remained independently associated with outcome (aHR: 4.7 (95%CI: 1.8-12.6, p = 0.002). In conclusion, this 5-year follow-up study is the first to prospectively confirm the association of elevated hs-cTnT and adverse outcomes. In addition to established clinical variables, cTn seems the biomarker of interest to further improve risk prediction in HC, which should be evaluated in larger prospective registries.

Topics: Aged; Blood Proteins; Cardiomyopathy, Hypertrophic; Cohort Studies; Death, Sudden, Cardiac; Defibrillators, Implantable; Electric Countershock; Female; Follow-Up Studies; Galectins; Growth Differentiation Factor 15; Heart Failure; Hospitalization; Humans; Interleukin-1 Receptor-Like 1 Protein; Magnetic Resonance Imaging; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Prognosis; Prospective Studies; Stroke; Tachycardia, Ventricular; Troponin T

Increased plasma concentration of N-terminal-prohormone B-type natriuretic peptide (NT-proBNP) can be detected in cats with cardiac disease. Potential effects of feline characteristics on NT-proBNP concentration may influence clinical usefulness.. To evaluate potential effects of feline characteristics on NT-proBNP plasma concentration and to compare NT-proBNP plasma concentrations in healthy cats with results in hypertrophic cardiomyopathy (HCM) cats with or without left atrial enlargement (LAE) using an ELISA and a point-of-care test (POCT), and assess if POCT results reflect ELISA results.. One hundred healthy cats of 3 breeds and 39 HCM cats were included.. Diseases other than HCM were excluded by physical examination, blood pressure measurement, echocardiography, hematology, and serum biochemistry.. Higher NT-proBNP concentrations were found in males than in females in healthy (P = .005) and in HCM cats (P = .0021), but breed had no effect on NT-proBNP concentrations. Using ≥100 pmol/L as a cutoff for abnormal samples, ELISA and POCT had similar sensitivity (SE; 72 and 74%) and specificity (SP; 97 and 98%) for detecting cats with HCM, cats with HCM and LAE (SE, both 100%; SP, 97 versus 98%), and cats with HCM without LAE (SE, both 69%; SP, 97 versus 98%), respectively, when compared to healthy cats.. Breed had no effect on plasma NT-proBNP concentrations, but higher concentrations were found in male than in female cats. The ELISA and POCT had similar SE and SP for detecting HCM. Both tests could identify all HCM cats with LAE but not all HCM cats without LAE.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Enzyme-Linked Immunosorbent Assay; Female; Male; Natriuretic Peptide, Brain; Peptide Fragments; Point-of-Care Testing; Sensitivity and Specificity; Species Specificity

Left-sided congestive heart failure (CHF) is characterized by increased filling pressures and related Doppler echocardiographic (DE) filling patterns.. Doppler echocardiographic variables of left ventricular filling derived from transmitral flow, pulmonary vein flow, and tissue Doppler can be used to detect CHF in cats with hypertrophic cardiomyopathy (HCM).. Forty-seven client-owned cats.. Prospective clinical cohort study. Cats underwent physical examination, thoracic radiography, analysis of N-terminal pro-brain natriuretic peptide (NT-proBNP), and transthoracic echocardiography and were divided into 3 age-matched groups: Group 1 (apparently healthy control), Group 2 (preclinical HCM), and Group 3 (HCM and CHF). Measured and calculated variables included respiratory rate, DE estimates, serum NT-proBNP concentration, and radiographic CHF score. Groups were compared using ANOVA, and receiver operating characteristic (ROC) curve and multivariate analyses were used to identify diagnostic cutoffs for the detection of CHF.. Fifteen cats were in Group 1, 17 in Group 2, and 15 in Group 3. The ROC analysis indicated that the ratio of peak velocity of early diastolic transmitral flow to peak velocity of late diastolic transmitral flow (area under the curve [AUC], 1.0; diagnostic cutoff, 1.77; P = .001), ratio of left atrial size to aortic annular dimension (AUC, 0.91; diagnostic cutoff, 1.96; P = .003), left atrial diameter (AUC, 0.89; cutoff, 18.5 mm; P = .004), diastolic functional class (AUC, 0.89; cutoff, class 2; P = .005), respiratory (AUC, 0.79; cutoff, 36 breaths per minute [brpm]; P = .02), and the ratio of the peak velocity of fused early and late transmitral flow velocities to the peak velocity of the fused early and late diastolic tissue Doppler waveforms (AUC, 0.74; cutoff, 15.1; P = .05) performed best for detecting CHF.. Various DE variables can be used to detect CHF in cats with HCM. Determination of the clinical benefit of such variables in initiating treatments and assessing treatment success needs further study.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Cohort Studies; Echocardiography, Doppler; Female; Heart Failure; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Respiratory Rate

Although elevated B-type natriuretic peptide (BNP) levels predict outcome in patients with hypertrophic cardiomyopathy (HCM), the association between BNP levels and outcome in patients with the apical phenotype of HCM remains unclear. We evaluated the impact of elevated BNP levels on outcome in a cohort of apical HCM patients.. Among 432 HCM patients, 144 with an apical phenotype were examined. Plasma BNP levels were measured at the time of the initial evaluation.. The median (interquartile range) BNP level at initial evaluation in these patients was 188.5 (72.0-334.4) pg/mL. During a median follow-up period of 9.5 years, 34 patients experienced HCM-related adverse outcomes, including 2 patients with sudden death, 5 with appropriate implantable defibrillator shocks, 3 with stroke-related death, 8 with non-fatal stroke, and 16 with heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis of the prognostic value of BNP for the combined endpoint gave an area under the ROC curve of 0.756, and optimal BNP cut-off point of 226.0pg/mL. Patients with high BNP levels (≥226.0pg/mL) were at significantly greater risk of the combined endpoint (log-rank p<0.001) than patients with low BNP levels. Multivariable analysis that included BNP levels and potential confounders showed that high BNP levels were an independent determinant of the combined endpoint (adjusted hazard ratio: 3.71; p=0.002).. Measuring BNP may help stratify the risk of HCM-related adverse outcome in apical HCM patients.

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Phenotype; Prognosis; ROC Curve

Disopyramide reduces the left ventricular outflow tract (LVOT) pressure gradient and improves symptoms in humans with hypertrophic obstructive cardiomyopathy (HOCM). However, the efficacy of disopyramide in cats has not been reported. We treated a cat with HOCM with carvedilol and disopyramide cotherapy and monitored the changes in LVOT flow velocity and N-terminal pro B-type natriuretic peptide (NT-proBNP) concentration. A 10-month-old neutered male Norwegian Forest cat was referred with a moderate systolic cardiac murmur. Echocardiography revealed thickening of the left ventricular wall, systolic anterior motion of the mitral valve leaflets, and turbulent aortic flow in the LVOT at systole. The LVOT flow velocity was 5.6 m/s. The plasma NT-proBNP concentration exceeded 1,500 pmol/L. The cat was diagnosed with HOCM and the β-blocker carvedilol was started and gradually increased to 0.30 mg/kg, bid. After 57 days, the LVOT flow velocity (4.8 m/s) and plasma NT-proBNP concentration (870 pmol/L) had decreased but remained elevated. Therefore, disopyramide was added at 5.4 mg/kg po bid and increased to 10.9 mg/kg po bid after 22 days. After 141 days of carvedilol and disopyramide treatment, the systolic anterior motion of the mitral valve leaflets had disappeared and the LVOT flow velocity and plasma NT-proBNP concentration had decreased to 0.7 m/s and 499 pmol/L, respectively. No adverse effect has been observed during the follow-up. Disopyramide might relieve feline LVOT obstruction after only partial response to a beta-blocker. Further large-scale studies are required to investigate the efficacy and safety of disopyramide use in cats with moderate to severe HOCM.

Topics: Adrenergic beta-Antagonists; Animals; Cardiomyopathy, Hypertrophic; Carvedilol; Cat Diseases; Cats; Disopyramide; Echocardiography; Male; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Outflow Obstruction; Voltage-Gated Sodium Channel Blockers

N-terminal pro B-type natriuretic peptide (NT-proBNP) and cardiac troponin-I (cTnI) are biomarkers commonly evaluated in cats with suspected heart disease. Many cats with hypertrophic cardiomyopathy (HCM) have systolic anterior motion of the mitral valve (SAM), but its influence on circulating NT-proBNP or cTnI concentrations is currently unknown.. Cats with HCM and SAM (HCM. One hundred forty cats with HCM: 70 with SAM and 70 without SAM.. Retrospective case-to-case study. Cats were recruited if diagnosed with HCM by echocardiography and results were available for NT-proBNP or cTnI concentrations or both. Cats with SAM were matched to those without SAM for clinical presentation, left atrial (LA) size and left ventricular (LV) fractional shortening.. For cats with HCM and equivalent LA size and LV systolic function, those with SAM had higher NT-proBNP and cTnI concentrations than did those without SAM. Presence of SAM should be considered when interpreting biomarker concentrations in cats with HCM.

Topics: Animals; Biomarkers; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Female; Male; Mitral Valve; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Troponin I

N-terminal probrain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure in hypertrophic cardiomyopathy (HCM). Mid-regional proatrial natriuretic peptide (MR-proANP) is a stable by-product of production of atrial natriuretic peptide. We sought to compare the prognostic value of MR-proANP and NT-proBNP in HCM.. We prospectively enrolled a cohort of patients with HCM from different European centres and followed them. All patients had clinical, ECG and echocardiographic evaluation and measurement of MR-proANP and NT-proBNP at inclusion.. Of 357 patients enrolled, the median age was 52 (IQR: 36-65) years. MR-proANP and NT-proBNP were both independently associated with age, weight, New York Heart Association (NYHA) class, left ventricular ejection fraction (LVEF), wall thickness and left atrial dimension. During a median follow-up of 23 months, 32 patients had a primary end point defined as death (n=6), heart transplantation (n=8), left ventricular assist device implantation (n=1) or heart failure hospitalisation (n=17). Both NT-proBNP and MR-proANP (p<10. MR-proANP emerges as a valuable biomarker for the prediction of death and heart failure related events in patients with HCM.

Topics: Adult; Aged; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Hypertrophic; Cause of Death; Disease Progression; Europe; Female; Heart Failure; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Prospective Studies; Reproducibility of Results; Risk Factors; Time Factors

Osteopontin (OPN) is an extracellular matrix glycoprotein that plays a role in a variety of cellular activities associated with inflammatory and fibrotic responses. Increased OPN levels in myocardium and plasma have been demonstrated in patients with dilated cardiomyopathy (DCM). However, nothing is known about OPN levels in patients with hypertrophic cardiomyopathy (HCM). Therefore, the aim of our study was to compare plasma OPN levels in patients with these two most common cardiomyopathies.. We examined plasma OPN as well as creatinine, C‑reactive protein (CRP), brain-type natriuretic peptide (BNP), and troponin I levels in 64 patients with DCM, 43 patients with HCM, and 75 control subjects. Transthoracic echocardiography was also performed on all cardiomyopathy patients.. Plasma OPN levels were significantly elevated in patients with DCM compared with HCM patients (95 ± 43 vs. 57 ± 21 ng/ml; p < 0.001) and control subjects (54 ± 19 ng/ml; p < 0.001); however, there was no difference between HCM patients and control subjects. New York Heart Association (NYHA) class III or IV disease was more frequently present in DCM patients than in HCM subjects (44 % vs. 2 %, p < 0.0001). In multivariate analysis, BNP and CRP levels together with NYHA class were found to be significant predictors of plasma OPN levels in DCM patients (p = 0.002, p = 0.029, and p < 0.001 for BNP, CRP, and NYHA, respectively).. Plasma OPN levels were associated with overall heart failure severity rather than with specific cardiomyopathy subtype in patients suffering from DCM or HCM, respectively.

Topics: Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Osteopontin

Some patients with hypertrophic cardiomyopathy (HCM) develop systolic dysfunction, called the dilated phase of HCM (d-HCM), which is associated with increased morbidity and mortality. We conducted a retrospective study using an HCM database to clarify the incidence, clinical characteristics, and long-term outcomes of d-HCM. We analyzed an HCM cohort consisting of 434 patients (273 with apical HCM and 161 with non-apical HCM; 18 had obstructive HCM, 16 had dilated HCM, and 127 had other HCM) diagnosed by echocardiography in our hospital between 1991 and 2010. The follow-up period was 8.4 ± 6.7 years. The mean age at final follow-up was 67 ± 14 years, and 304 patients (70%) were men. The mean age of the 16 d-HCM patients at the initial visit was 45 ± 17 years, the age at final follow-up was 59 ± 18 years, and 13 were men. Thirteen d-HCM patients developed atrial fibrillation and six patients developed ischemic stroke. Twelve d-HCM patients were implanted with cardiac devices: one pacemaker, nine implantable cardioverter-defibrillators, and two cardiac resynchronization therapy with defibrillator. Five patients died of progressive heart failure at the age of 61 ± 23 years. The age at the initial visit and final follow-up were lower and the NYHA class, brain natriuretic peptide levels, and left ventricular function at initial evaluation were worse in the d-HCM group. Univariate analysis demonstrated that a lower age at the initial visit was associated with d-HCM (hazard ratio 0.955/1 year increase; 95% CI 0.920-0.991, P = 0.015). In our HCM cohort, the incidence of d-HCM was 4%. A high prevalence of atrial fibrillation and cerebral infarction and poor prognosis were noted in this group, despite patients undergoing medication and device implantation.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Biomarkers; Cardiac Resynchronization Therapy; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Defibrillators, Implantable; Echocardiography; Female; Follow-Up Studies; Heart Failure; Humans; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Pacemaker, Artificial; Retrospective Studies; Stroke; Survival Analysis; Ventricular Function, Left

Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Data regarding the correlations of biomarkers and AF in HCM patients are rather limited. We sought to explore the associations between the presence of AF and circulating biomarkers reflecting cardiovascular function (N-terminal pro-brain natriuretic peptide, NT-pro BNP), endothelial function (big endothelin-1, big ET-1), inflammation (high-sensitivity C-reactive protein), and myocardial damage (cardiac troponin I, cTnI) in HCM patients with and without left ventricular outflow tract obstruction (LVOTO).In all, 375 consecutive HCM in-hospital patients were divided into an AF group (n = 90) and a sinus rhythm (SR) group (n = 285) according to their medical history and electrocardiogram results.In comparison with the SR group, peripheral concentrations of big ET-1, NT-pro BNP, and cTnI were significantly higher in patients with AF. Only the biomarker of big ET-1, together with palpitation and left atrial diameter (LAD), was independently associated with AF in HCM patients. Ln big ET-1 was positively related to Ln NT-pro BNP, LAD, and heart rate, but negatively related to left ventricular ejection fraction. Combined measurements of big ET-1 ≥ 0.285 pmol/L and LAD ≥ 44.5 mm indicated good predictive values in the presence of AF, with a specificity of 94% and a sensitivity of 85% in HCM patients.Big ET-1 has been identified as an independent determinant of AF, regardless of LVOTO, and is significantly related to parameters representing cardiac function and remodeling in HCM. Big ET-1 might be a valuable index to evaluate the clinical status of AF in HCM patients.

Topics: Atrial Fibrillation; Biomarkers; C-Reactive Protein; Cardiomyopathy, Hypertrophic; China; Correlation of Data; Echocardiography; Electrocardiography; Endothelin-1; Female; Heart Atria; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Retrospective Studies; Stroke Volume; Troponin I; Ventricular Outflow Obstruction; Ventricular Remodeling

Topics: Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Heart Septum; Humans; Natriuretic Peptide, Brain

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis

Topics: Anti-Arrhythmia Agents; Antineoplastic Agents; Cardiomyopathy, Hypertrophic; Cardiovascular Agents; Drug Repositioning; Echocardiography; Gene Expression Regulation; Heart Valves; Heterozygote; Humans; Infant; MAP Kinase Kinase 1; Mutation; Natriuretic Peptide, Brain; Noonan Syndrome; Peptide Fragments; Propranolol; Protein Kinase Inhibitors; Pyridones; Pyrimidinones; ras Proteins; Signal Transduction; Treatment Outcome

To test dual blood biomarkers compared with electrocardiogram (ECG) for hypertrophic cardiomyopathy (HC) screening, we performed 3 analyses and cut-point assessments. First, we measured platelet function analyzer (PFA)-100 (n = 99) and normalized B-type natriuretic peptide (BNP) or NT-proBNP (BNP/upper limit of normal [ULN], n = 92) in 64 patients with HC and 29 normal controls (NCs). Second, from the regression equation between PFA and gradient (r = 0.77), we derived estimated PFA in a population of 189 patients with functional class I HC in whom measured BNP/ULN and ECG were available, and calculated single and dual biomarker sensitivity and specificity compared with ECG. Finally, we compared BNP/ULN in class I patients based on mutation and familial history status. In 42 patients with obstructive HC versus NCs, there was a slight overlap of PFA and BNP/ULN, but for the product of PFA × BNP/ULN, there was near-complete separation of values. Among patients with class I obstructive HC, estimated PFA × BNP/ULN had a sensitivity of 93% and a specificity of 100%; in latent and nonobstructive HC, sensitivity dropped to 61% and 72%; for ECG in obstructive, latent, and nonobstructive HC, sensitivity was 71%, 34%, and 67%. Functional class I patients with positive (n = 28) and negative (n = 36) sarcomere mutations and a positive (n = 71) or a negative (n = 109) family history had significant elevations of BNP/ULN versus NC, with no between-group differences. In conclusion, PFA and BNP were highly associated with obstructive HC and could potentially be used for screening; BNP was not uniquely elevated in patients with familial versus nonfamilial or mutation-positive versus mutation-negative HC.

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Echocardiography; Electrocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Platelet Function Tests; Predictive Value of Tests; Prospective Studies; Retrospective Studies; Sensitivity and Specificity

To investigate the association between serum omentin-1 levels and adverse cardiac events in patients with hypertrophic cardiomyopathy (HCM).. This prospective, observational study included 87 patients with HCM and 50 age- and sex-matched control subjects. Serum omentin-1 and brain natriuretic peptide (BNP) levels were measured in all subjects, using enzyme-linked immunosorbent assay and electrochemiluminescence, respectively. Patients with HCM were divided into 2 groups according to their omentin levels, i.e., low: ≤291 ng/mL (n = 48) and high: > 291 ng/mL (n = 39). Cardiac mortality, hospitalization due to heart failure, and implantable cardioverter-defibrillator (ICD) implantation were considered adverse cardiac events. Statistical analysis included uni- and multivariant logistic regression, receiver-operating characteristic (ROC) analysis, and the Kaplan-Meier method.. Serum omentin-1 levels were significantly lower in the obstructive (253.9 ± 41.3 ng/mL) and nonobstructive (301.9 ± 39.8 ng/mL) HCM groups than in the control group (767.1 ± 56.4 ng/mL), p < 0.001, respectively. The BNP levels were higher in the obstructive and nonobstructive HCM groups than in the control group (269.5 ± 220, 241.0 ± 227, and 24.0 ± 18.9 pg/mL, respectively, p < 0.001). The Kaplan-Meier analysis indicated that patients with low omentin-1 levels showed a significantly higher (48.2%) 2-year cumulative incidence of overall adverse cardiac events than those with high omentin-1 levels (16.2%) (log-rank test, p  =  0.001). In the multivariate logistic regression analysis, omentin-1, interventricular septum (IVS) thickness, and male gender were independent predictors of adverse cardiac events in the follow-up.. Omentin-1 levels were lower in patients with HCM than in the control group, and this was associated with worse cardiac outcomes.

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; GPI-Linked Proteins; Humans; Lectins; Logistic Models; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Risk Assessment; Risk Factors; Sex Distribution; Turkey

The association between B-type natriuretic peptide (BNP) levels and sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM) remains unclear.. This study evaluated the effect of elevated BNP levels on sudden death risk in a cohort of patients with HCM.. This study included 346 patients with HCM. Plasma BNP levels were measured at the initial evaluation.. The median (interquartile range) BNP level in the study patients was 197.2 (84.4-353.3) pg/mL. During a median (interquartile range) follow-up period of 8.4 (4.2-12.5) years, 37 patients (10.7%) experienced the combined end point of sudden death or potentially lethal arrhythmic events, including 11 patients with sudden death (3.2%), 8 resuscitated after cardiac arrest, and 18 with appropriate implantable defibrillator shocks. Time-dependent receiver operating characteristic curve analysis of the prognostic value of BNP for the combined end point showed that the Harrell's concordance index was 0.748 and the optimal BNP cutoff point was 312 pg/mL. Patients with high BNP levels (>312 pg/mL) were at a significantly higher risk of sudden death (Gray test, P = .001) and the combined end point (Gray test, P < .001) than were patients with low BNP levels (≤312 pg/mL). Multivariable analysis that included BNP levels and established risk factors for sudden death showed that high BNP levels were an independent determinant of the combined end point (adjusted hazard ratio 5.71; 95% confidence interval 2.86-11.4; P < .001).. Elevated BNP levels may be associated with sudden death and the combination of sudden death or potentially lethal arrhythmic events in patients with HCM.

Topics: Biomarkers; Cardiomyopathy, Hypertrophic; Death, Sudden, Cardiac; Female; Follow-Up Studies; Humans; Incidence; Japan; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Risk Assessment; Risk Factors; ROC Curve; Survival Rate

Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice.. The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM.. Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis.. We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r = 0.32, p = 0.012), LV mass indexed for the body surface area (LVMI) (r = 0.27, p = 0.036) and maximal wall thickness (MWT) (r = 0.31, p = 0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r = 0.58, p < 0.0001), LVMI (r = 0.48, p = 0.0001), MWT (r = 0.31, p = 0.015) and late gadolinium enhancement (LGE) mass (r = 0.37, p = 0.003). There were positive correlations between NT-proBNP levels and LVM (r = 0.33, p = 0.01), LVMI (r = 0.41, p = 0.001), MWT (r = 0.42, p < 0.001) and LGE mass (r = 0.44, p < 0.001).. Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Fibrosis; Humans; Hypertrophy; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Troponin T

Hypertrophic cardiomyopathy (HC) is a heterogenous disease with a variable clinical course. Predictors of long-term adverse cardiovascular events are needed. Our objectives were to determine the long-term prognostic value of a single and serial point of care (POC) B-type natriuretic-peptide (BNP) measurements in HC. One hundred and eleven ambulatory patients with HC (mean age 53 ± 16 years) were prospectively recruited over a 2-year period (2004 to 2006). A clinical assessment, comprehensive echocardiogram, and a POC BNP level was obtained at baseline and at a 1- to 2-year follow-up. They were subsequently followed for the occurrence of major adverse cardiac events (MACE). The median baseline BNP concentration was 114 pg/ml (range 5.3 to 1550 pg/ml). During a mean follow-up of 6.2 ± 3.4 years, 42 patients (38%) had a MACE. In a multivariable Cox model including clinical and echocardiographic predictors, logBNP (HR 4.30; 95% confidence interval 1.97 to 9.37, p <0.001) and left ventricualr ejection fraction (LVEF) (HR 0.96; 95% confidence interval 0.94 to 0.99, p = 0.011) remained significant predictors of MACE. Nested models demonstrated incremental prognostic value of logBNP for MACE (chi-square increased from 4.3 to 22.8, p <0.01) over clinical and echocardiographic factors. Patients with persistently elevated BNP (>100 pg/ml) at baseline and at the second visit were at a higher risk of developing MACE during follow-up (5-year MACE-free survival of 0.91 (SE 0.06) vs 0.45 (SE 0.09), p <0.001). In conclusion, POC BNP levels in patients with HC were predictive of long-term MACE and had independent and incremental value. Patients with persistently elevated BNP levels were at a higher risk of MACE.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Point-of-Care Systems; Predictive Value of Tests; Prognosis; Prospective Studies; Risk Factors

BACKGROUND Dracocephalum heterophyllum Benth flavonoid (DHBF) is a Tibetan and Uighur traditional medicine used to treat various disorders such as hypertension, lung heat, cough, and bronchitis; it has good antioxidant activity. Previous studies have shown that DHBF can reduce blood pressure in renovascular hypertensive rats, improve left ventricular systolic and diastolic function, and improve myocardial contractility. Therefore, we aimed to study the effect of DHBF on cardiomyocyte hypertrophy in cultured cells. MATERIAL AND METHODS Neonatal rat cardiomyocytes were cultured, and hypertrophy was induced by angiotensin II (Ang II), with or without varying concentrations of the DHBF extract. Cell Counting Kit-8 assay was used to assess cell viability, RT-qPCR was used to determine mRNA levels, confocal laser scanning microscopy was used to measure cell surface area and intracellular Ca2+ concentrations ([Ca2+]i), and colorimetric assays were used to assess nitric oxide (NO) levels and nitric oxide synthase (NOS) activity. RESULTS Ang II treatment of cardiomyocytes reduced cell viability to ~75% that of controls. Ang II treatment also increased cell surface area; increased mRNA expression of c-jun, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC); increased [Ca2+]i; and reduced NOS activity and NO production. DHBF treatment could reverse these effects in a concentration-dependent manner. CONCLUSIONS These results showed that DHBF can ameliorate cardiomyocyte hypertrophy induced by Ang II, as indicated by the downregulation of cardiac hypertrophy genes (ANP, BNP, and β-MHC) and reduction in cell surface area. The mechanism may be related to NO release and [Ca2+]I regulation.

Topics: Angiotensin II; Animals; Animals, Newborn; Atrial Natriuretic Factor; Cardiomegaly; Cardiomyopathy, Hypertrophic; Cells, Cultured; China; Flavonoids; Heart Ventricles; Medicine, Tibetan Traditional; Myocardium; Myocytes, Cardiac; Natriuretic Peptide, Brain; Primary Cell Culture; Rats; Rats, Sprague-Dawley; Signal Transduction

The relations of elevated N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac ischemia in hypertrophic cardiomyopathy (HCM) patients is uncertain. Therefore we designed the study with the following aims: (1) to analyze plasma concentrations of NT-pro-BNP in various subsets of HCM patients; (2) to reveal the correlations of NT-pro-BNP, myocardial ischemia, and diastolic dysfunction; (3) to assess predictors of the elevated plasma levels of NT-pro-BNP.. In 61 patients (mean age 48.9±16.3 years; 26 male) with asymmetric HCM plasma levels of NT-pro-BNP were obtained. Standard transthoracic examination, tissue Doppler echocardiography with measurement of transthoracic coronary flow velocity reserve (CFVR) in left anterior descending artery (LAD) was done. Mean natural logarithm value of NT-pro-BNP was 7.11±0.95pg/ml [median value 1133 (interquartile range 561-2442)pg/ml]. NT-pro-BNP was significantly higher in patients with higher NYHA class, in obstructive HCM, more severe mitral regurgitation, increased left atrial volume index (LAVI), presence of calcified mitral annulus, elevated left ventricular (LV) filling pressure and in decreased CFVR. Levels of NT-pro-BNP significantly correlated with the ratio of E/e' (r=0.534, p<0.001), LV outflow tract gradient (r=0.503, p=0.024), LAVI (r=0.443, p<0.001), while inversely correlated with CFVR LAD (r=-0.569, p<0.001). When multivariate analysis was done only CFVR LAD and E/e' emerged as independent predictors of NT-pro-BNP.. Plasma levels of NT-pro-BNP were significantly higher in HCM patients with more advanced disease. Elevated NT-pro-BNP not only reflects the diastolic impairment of the LV, but it might also be the result of cardiac ischemia in patients with HCM.

Topics: Adult; Aged; Cardiomyopathy, Hypertrophic; Coronary Circulation; Diastole; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Mitral Valve Insufficiency; Multivariate Analysis; Myocardial Ischemia; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, 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

The aim is to investigate autonomic nervous system imbalance in hypertrophic cardiomyopathy (HCM) by combining echocardiographic morphological and functional parameters with the analysis of the autonomic responses to orthostatic stress.. A 10-min tilting test and a transthoracic echocardiogram focused on ventricular septal systolic (S wave) and diastolic function (isovolumic relaxation time) were performed. Low frequency on high frequency ratio (LF/HF) and RR variation (variation of beat to beat intervals) in response to passive orthostatism were used as measures of sympathetic reflex activation [delta LF/HF (D-LF/HF) and delta RR (DRR), respectively]. Brain natriuretic peptide was measured.. A total of 50 HCM patients were categorized in two groups: D-LF/HF more than 0 (group 1, sympathetic response) and D-LF/HF 0 or less (group 2, parasympathetic response). Patients in group 2 had higher New York Heart Association class, a more frequent history of atrial fibrillation (38 versus 9% P = 0.04) or syncope (46 versus 12% P = 0.01) and an increased septal isovolumic relaxation time (122 versus 82 ms P = 0.02). The same categorization was made according to lowest quartile DRR (DRR at least 23 ms, group 1: sympathetic response; DRR less than 23 ms, group 2: parasympathetic response). In group 2, patients were older, with advanced New York Heart Association class and higher history of atrial fibrillation.. Autonomic response to passive orthostatism in HCM appears correlated with specific functional features of the hypertrophic heart. Altered neural afferent traffic from the localized area of segmental hypertrophy resulted in autonomic changes with a blunted sympathetic response, and an inappropriate vagal activation, especially in patients with history of atrial fibrillation or syncope.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Diastole; Echocardiography, Doppler, Color; Female; Heart; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Orthostatic Intolerance; Posture; Predictive Value of Tests; Reflex; Sympathetic Nervous System; Systole; Tilt-Table Test; Vagus Nerve; Ventricular Function, Left

Correlation of increased copeptin levels with various cardiovascular diseases has been described. The clinical use of copeptin levels in patients with hypertrophic cardiomyopathy (HCM) has not been investigated before.. In this study, we aimed to investigate the prognostic value of copeptin levels in patients with hypertrophic cardiomyopathy (HCM).. HCM was defined as presence of left ventricular wall thickness ≥15 mm in a subject without any concomitant disease that may cause left ventricular hypertrophy. Levels of copeptin and plasma N-terminal probrain natriuretic peptide (NT-proBNP) were evaluated prospectively in 24 obstructive HCM patients, 36 nonobstructive HCM patients, and 36 age- and sex-matched control subjects. Blood samples were collected in the morning between 7 and 9 am after overnight fasting. Patients were followed for 24 months. Hospitalization with diagnosis of heart failure/arrhythmia, implantable cardioverter-defibrillator implantation, and cardiac mortality were accepted as adverse cardiac events.. Copeptin and NT-proBNP levels were higher in the HCM group compared with controls (14.1 vs 8.4 pmol/L, P < 0.01; and 383 vs 44 pg/mL, P < 0.01, respectively). Copeptin and NT-proBNP levels were higher in the obstructive HCM subgroup compared with the nonobstructive HCM subgroup (18.3 vs 13.1 pmol/L, P < 0.01; and 717 vs 223 pg/mL, P < 0.01, respectively). In multivariable logistic regression analysis, copeptin and NT-proBNP levels remained as independent predictors of heart failure (P < 0.01 for both) and adverse cardiac events (P < 0.01 for both).. Copeptin and NT-proBNP levels were significantly higher in patients with obstructive HCM, and higher levels were associated with worse outcome.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography; Female; Follow-Up Studies; Glycopeptides; Heart Ventricles; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Survival Rate; Time Factors; Turkey

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Atrial Remodeling; Biomarkers; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Catheter Ablation; Female; Heart Atria; Heart Diseases; Humans; Hypertension; Imaging, Three-Dimensional; Male; Middle Aged; Natriuretic Peptide, Brain; Pulmonary Veins; Tomography, X-Ray Computed; Troponin T; Vascular Remodeling

NT-proBNP level is a predictive factor in hypertrophic cardiomyopathy patients, in which left ventricular outflow tract obstruction contributes to an increased NT-proBNP level. However, studies regarding the influence of septal myectomy on NT-proBNP level in hypertrophic obstructive cardiomyopathy are lacking.. One hundred and eighty-two patients who underwent septal myectomy in Fuwai Hospital from May 2011 to March 2016 and were included in the present study. Preoperative and follow-up NT-proBNP was retrospectively collected. Correlation analysis was performed to determine the factors affecting preoperative NT-proBNP and postoperative decrease.. The cohort had a median age of 46.2 [IQR: 36.5-53.1] years, and 106 (58.2%) patients were male. NT-proBNP decreased to 816.5 [IQR: 400.3-1661.8] pg/mL from preoperative 1732.4 [IQR: 819-3296.5] pg/mL (p<0.001). Baseline NT-proBNP was correlated with gender (p<0.001), maximum septal thickness (p<0.001), and resting pressure gradient (p=0.006). The extent of NT-proBNP decrease was positively correlated with age (p<0.001), baseline NT-proBNP (p<0.001), follow-up time (p=0.020), and enlargement of the ascending aorta (p=0.019). NT-proBNP exhibited a persistent decrease after myectomy.. Myectomy significantly reduced NT-proBNP level in hypertrophic obstructive cardiomyopathy patients, in which a time-dependent manner of decrease indicated myocardial remodeling of the heart after myectomy.

Topics: Adult; Age Factors; Cardiomyopathy, Hypertrophic; Echocardiography; Female; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Preoperative Period; Retrospective Studies

Cibenzoline, a class Ia antiarrhythmic drug, is useful for reducing the left ventricular pressure gradient (LVPG) in patients with hypertrophic obstructive cardiomyopathy (HOCM). However, chronic effects of cibenzoline on LVPG and left ventricular (LV) remodeling are unknown.. Forty-one patients with HOCM participated in this study. Echocardiographic, electrocardiographic, and brain natriuretic peptide (BNP) data collected before and after cibenzoline treatment were compared. From the relation between LVPG and plasma concentration of cibenzoline, an efficacious plasma concentration of cibenzoline was estimated.. The mean follow-up period was 74.2±47.1 months. The LVPG decreased from 104.8±62.6mmHg to 27.6±30.5mmHg (p<0.0001). The LV end-diastolic dimension increased from 42.8±5.8mm to 46.2±5.4mm (p<0.0001), but neither LV end-systolic dimension nor LV fractional shortening changed significantly. The left atrial dimension decreased from 40.0±4.7mm to 36.2±5.1mm (p<0.0001). The E-wave velocity/A-wave velocity ratio increased, early diastolic annular velocity (Ea) increased, and E/Ea ratio decreased. The interventricular septal wall thickness, LV posterior wall thickness, the Sokolow-Lyon index, and the depth of negative T wave decreased. The heart rate-corrected QT interval was shortened. Plasma BNP level decreased from 418.8±423.7pg/ml to 213.7±154.1pg/ml (p<0.02). The safe and efficacious plasma concentration of cibenzoline was between 300ng/mL and 1500ng/mL.. Long-term treatment with cibenzoline attenuated LVPG, improved LV diastolic dysfunction, and induced LV hypertrophy regression in patients with HOCM without causing serious complications.

Topics: Aged; Anti-Arrhythmia Agents; Cardiomyopathy, Hypertrophic; Echocardiography; Electrocardiography; Female; Follow-Up Studies; Humans; Hypertrophy, Left Ventricular; Imidazoles; Male; Middle Aged; Natriuretic Peptide, Brain; Time; Ventricular Function, Left; Ventricular Pressure; Ventricular Remodeling

We evaluated whether left atrial (LA) phasic functions, P-wave dispersion (PWD), and plasma NT-proBNP levels could predict future development of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM).. Seventy patients with HCM were evaluated. The LA phasic functions including the LA total emptying volume (LATEV), LA total emptying fraction (LATEF), LA active emptying volume (LAAEV), LA active emptying fraction (LAAEF), LA passive emptying volume (LAPEV), and LA passive emptying fraction (LAPEF) were evaluated. P-wave dispersion was calculated. Plasma NT-proBNP levels were measured on the same day with echocardiographic study.. Patients were followed up 53.09 ± 1.87 months. Patients who developed AF (n = 18) had significantly higher PWD values, NT-proBNP levels, LAVI, E/E' av, and resting LVOT gradients and significantly lower LATEF and LAAEF. In multivariate analysis, LATEF (P = 0.002), LAAEF (P = 0.007), logNT-proBNP level (P = 0.022), and PWD (P = 0.018) were associated with AF development. The results of receiver operating characteristic analysis revealed that a LATEF cutoff value 49% with 72% sensitivity and 81% specificity, a LAAEF cutoff value of 36% with 72% sensitivity and 71% specificity, and an NT-proBNP cutoff value of 720 pg/mL predicted future AF development with 72% sensitivity and 60% specificity. A PWD cutoff value of 47.5 msecond predicted future AF development with 78% sensitivity and 72% specificity.. In patients with HCM, LA phasic functions, PWD, and NT-proBNP levels predict future development of AF. Assessment of LA phasic functions during routine echocardiographic evaluation and measuring NT-proBNP levels and PWD values of patients with HCM during daily practice may provide important data in predicting those at high risk of AF occurrence.

Topics: Atrial Fibrillation; Biomarkers; Cardiomyopathy, Hypertrophic; Causality; Comorbidity; Echocardiography; Electrocardiography, Ambulatory; Female; Follow-Up Studies; Humans; Incidence; Longitudinal Studies; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Reproducibility of Results; Risk Factors; Sensitivity and Specificity; Stroke Volume; Turkey

Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM.. Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis.. LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6-2340.8] vs. 866.6 [707.2-1875.2] pmol/L, P = 0.003; 0.024 [0.010-0.049] vs. 0.010 [0.005-0.021] ng/ml, P <0.001, respectively). The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001) and log NT-proBNP (r = 0.211, P = 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025 ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%.. Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Female; Fibrosis; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Troponin I

In this study, we investigated the association between brain natriuretic peptide (BNP) levels and tissue Doppler imaging measurements and also screening for deadly mutations in patients with hypertrophic cardiomyopathy (HCM). We enrolled 20 patients diagnosed with HCM (age:10.7±5 years (1-17), 85% male, weight:42.25±23.10 kg, height:141.80±32.45 cm) and 20 age, gender and body weight-matched control subjects. We performed electrocardiography, transthoracic echocardiography, and tissue Doppler echocardiography in each group, as well as genetic tests (for Arg403Gln, Arg453Cys, Arg719Trp and Arg719Gln mutations in MYH7 Exons 13, 14, 19) and BNP in the patients. The patients were divided into two groups according to the presence (Group 1) or absence (Group 2) of left ventricular (LV) outflow tract obstruction. QTc dispersion and the LV ejection fraction and left atrial (LA) volume index were increased in Group 1. The LA volume index and the mitral and septal E/Ea ratio and septum Z-score were increased while the mitral lateral annulus and septal annulus Ea wave velocities and the mitral and tricuspid E/A ratio were decreased in patients with high levels of BNP compared to those with normal BNP levels. There were no mutations that are associated with increased risk of sudden death found in patients included in this study. In the light of our data, we conclude that such parameters BNP levels above the 98 pg/mL, septal thickness Z-score ˃6, and higher mitral and septal E/Ea ratios can be used for management of patients with HCM according to life-threatening conditions.

Topics: Adolescent; Cardiac Myosins; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Death, Sudden, Cardiac; Echocardiography, Doppler; Electrocardiography; Exons; Female; Heart Atria; Humans; Infant; Male; Mitral Valve; Mutation; Myosin Heavy Chains; Natriuretic Peptide, Brain; Risk; Tricuspid Valve; Ventricular Dysfunction, Left; Ventricular Function, Left

Objective Increased left ventricular mass (LVM) and LV fibrosis mass (LVFM) are characteristics of hypertrophic cardiomyopathy (HCM). Additionally, a substantial increase in the plasma B-type natriuretic peptide (BNP) level is observed. Therefore, we investigated the interrelationship and clinical significances of these parameters in a HCM cohort that underwent cardiac MRI (CMR). Methods Patients with HCM (n=109) receiving regular outpatient treatment underwent CMR and follow-up through 2015 from CMR examinations. The clinical outcome measures were all-cause mortality, admission for worsening heart failure, and ventricular tachycardia/fibrillation. Results The baseline body mass index (BMI), LV outflow tract (LVOT) obstruction, New York Heart Association (NYHA) class, and increased left atrial dimension (LAD) index were associated with the plasma BNP level. In the CMR analysis, LVM and LVFM indices significantly correlated with the BNP level (r=0.422 and 0.368, respectively), which were independent determinants according to a multivariate analysis (p=0.009 and 0.023, respectively). A Kaplan-Meier analysis during a median follow-up of 19.4 months showed that the baseline LVM or LVFM index was not associated with the clinical outcomes. However, the baseline BNP level was significantly associated with them (p<0.001). In addition, a multivariate Cox proportional hazard analysis showed that plasma BNP was an independent predictor for the clinical outcomes after adjusting for age, sex, LVM, and LVFM. Conclusion The LVM and LVFM are determinants of the BNP level independent of the BMI, LVOT obstruction, LAD, and NYHA class in patients with HCM. However, plasma BNP may be a more sensitive integrated-marker for the clinical outcomes than LVM or LVFM.

Topics: Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Female; Fibrosis; Heart Failure; Heart Ventricles; Humans; Incidence; Japan; Kaplan-Meier Estimate; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain

We evaluated the associations among the well-known atrial fibrillation (AF) predictors including P-wave dispersion (PWD), intra- and inter-atrial electromechanical dyssynchrony (EMD), left atrial (LA) phasic functions, and plasma N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels, in patients with hypertrophic cardiomyopathy (HCM).. Seventy patients with HCM and age and sex matched 70 subjects were enrolled. PWD, LA total emptying fraction (LATEFr), active emptying fraction (LAAEFr), passive emptying fraction (LAPEFr), expansion index (LAEI) intra- and inter-atrial EMD were calculated. Levels of NT-proBNP of all subjects were determined.. Higher PWD (p = 0.006), significantly decreased LAEI (p < 0.001), LATEFr, and LAPEFr (both p values < 0.001) values and significantly increased inter-atrial (p < 0.001), LA (p = 0.001), and right atrial dyssynchrony (p < 0.001) were observed in the HCM group compared to controls. PWD was negatively correlated with LAEI (r = -0.236, p = 0.005) and LATEFr (r = -0.242, p = 0.04), however not with LAPEFr (p = 0.7), or LAAEFr (p = 0.3). Except for the LA lateral wall PA' (r = 0.283, p = 0.02), PWD was not correlated with any atrial EMD parameter. Inter-atrial dyssynchrony was related to LAEI (r = -0.272, p = 0.001), LATEFr (r = -0.256, p = 0.03), and LAPEFr (r = -0.332, p = 0.006), but not, however, to LAAEFr (p = 0.4). The plasma NT-proBNP levels of patients were not correlated with either PWD (p = 0.927) or inter-atrial dyssynchrony (p = 0.102).. PWD and inter-atrial dysynchrony seem to independently promote AF, although both are associated with LA reservoir function in HCM populations. The NT-proBNP level is not associated with these two AF predictors in patients with HCM. NT-proBNP seems to be a poor marker of atrial electrical remodeling in HCM patients.

Topics: Adult; Atrial Fibrillation; Atrial Function, Left; Atrial Remodeling; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors

Hypertrophic cardiomyopathy (HCM) is characterized by inappropriate hypertrophy, myocyte disarray and increased interstitial fibrosis. The tumour necrosis factor-like weak inducer of apoptosis (TWEAK) is a cell surface cytokine with biological activities including stimulation of cell growth, induction of inflammatory cytokines and stimulation of apoptosis. There are controversial data about the potential role of TWEAK in different cardiovascular pathologies. NT-proBNP is an established biomarker of myocardial wall stress, associated with poor functional class in HCM. We hypothesized that effort capacity in patients with HCM could be related to serum levels of these biomarkers.. We included 40 haemodynamic stable HCM patients and 53 healthy controls with similar sex and age. We studied exercise capacity by maximal oxygen consumption in a limited treadmill exercise test. TWEAK and NT-proBNP were assayed by ELISA method and automated Elecsys® platform, respectively. We obtained 46 samples of myocardial tissues by septal myectomy in patients with HCM and evaluated myocardial fibrosis, immunoreaction with TWEAK antibody and apoptosis with TUNEL assay.. We found raised TWEAK and NT-proBNP serum levels in patients when compared with control levels (both P < 0.001). In a multivariate analysis, TWEAK and NT-proBNP levels, as well as sex, remained independently associated with the effort capacity (all P < 0.05). We found an association between immunoreaction degree and the degree of myocardial fibrosis (P = 0.021), as well as apoptosis (P = 0.002) in the tissue samples from patients undergoing septal myectomy.. TWEAK and NT-proBNP levels are biomarkers of disease severity independently associated with the effort capacity in patients with HCM.

Topics: Apoptosis; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Cytokine TWEAK; Exercise Tolerance; Female; Fibrosis; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; ROC Curve; Tumor Necrosis Factors

Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease characterized by ventricular hypertrophy, myocardial fibrosis, and impaired ventricular relaxation. The exact mechanisms by which fibrosis is caused remain unknown.. Circulating TGF-β is related to poor prognosis in HCM.. We compared TGF-β levels of 49 HCM patients with those of 40 non-HCM patients. We followed the patients with HCM for 18 months and divided them into 2 groups: low TGF-β (≤ 4877 pg/mL) and high TGF-β (> 4877 pg/mL). We compared the 2 groups in terms of brain natriuretic peptide (BNP), echocardiographic parameters, and clinical outcomes including myocardial infarction, arrhythmias, implantable cardioverter-defibrillator implantation, hospitalization, New York Heart Association (NYHA) class, acute heart failure, and mortality.. The HCM patients had higher TGF-β levels than those in the control group (P = 0.005). In the follow-up, those in the high TGF-β group had higher BNP levels, larger left-atrial size, thicker interventricular septum, NYHA class, more hospitalizations, and a greater number of clinical adverse events (P < 0.001, P = 0.01, P < 0.001, P = 0.002, P < 0.001 and P = 0.003, respectively). TGF-β level of > 4877 pg/mL can predict adverse events with a specificity of 75% and a sensitivity of 72% (P = 0.014). In multivariate regression analysis, TGF-β, BNP, and interventricular septum thickness were significantly associated with adverse events (P = 0.028, P = 0.030, and P = 0.034, respectively).. The TGF-β level is higher in HCM patients and associated with a poor prognosis in HCM.

Topics: Adult; Cardiomyopathy, Hypertrophic; Enzyme-Linked Immunosorbent Assay; Female; Hospitalization; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Transforming Growth Factor beta1; Ultrasonography; Young Adult

Diffuse myocardial fibrosis (DMF) is important in cardiovascular disease, however until recently could only be assessed by invasive biopsy. We hypothesised that DMF measured by T1 mapping is elevated in isolated systemic hypertension.. In a study of well-controlled hypertensive patients from a specialist tertiary centre, 46 hypertensive patients (median age 56, range 21 to 78, 52 % male) and 50 healthy volunteers (median age 45, range 28 to 69, 52 % male) underwent clinical CMR at 1.5 T with T1 mapping (ShMOLLI) using the equilibrium contrast technique for extracellular volume (ECV) quantification. Patients underwent 24-hours Automated Blood Pressure Monitoring (ABPM), echocardiographic assessment of diastolic function, aortic stiffness assessment and measurement of NT-pro-BNP and collagen biomarkers.. Late gadolinium enhancement (LGE) revealed significant unexpected underlying pathology in 6 out of 46 patients (13 %; myocardial infarction n = 3; hypertrophic cardiomyopathy (HCM) n = 3); these were subsequently excluded. Limited, non-ischaemic LGE patterns were seen in 11 out of the remaining 40 (28 %) patients. Hypertensives on therapy (mean 2.2 agents) had a mean ABPM of 152/88 mmHg, but only 35 % (14/40) had left ventricular hypertrophy (LVH; LV mass male > 90 g/m(2); female > 78 g/m(2)). Native myocardial T1 was similar in hypertensives and controls (955 ± 30 ms versus 965 ± 38 ms, p = 0.16). The difference in ECV did not reach significance (0.26 ± 0.02 versus 0.27 ± 0.03, p = 0.06). In the subset with LVH, the ECV was significantly higher (0.28 ± 0.03 versus 0.26 ± 0.02, p < 0.001).. In well-controlled hypertensive patients, conventional CMR discovered significant underlying diseases (chronic infarction, HCM) not detected by echocardiography previously or even during this study. T1 mapping revealed increased diffuse myocardial fibrosis, but the increases were small and only occurred with LVH.

Topics: Adult; Aged; Antihypertensive Agents; Biomarkers; Blood Pressure; Blood Pressure Monitoring, Ambulatory; Cardiomyopathy, Hypertrophic; Case-Control Studies; Collagen; Echocardiography, Doppler; Female; Fibrosis; Humans; Hypertension; Hypertrophy, Left Ventricular; Image Interpretation, Computer-Assisted; London; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Stroke Volume; Tertiary Care Centers; Ventricular Function, Left; Ventricular Remodeling; Young Adult

The signal peptide for human B-type natriuretic peptide preprohormone (BNPsp), which is released from cardiomyocytes, is increased in plasma of patients with acute myocardial infarction (AMI); however, its exact release kinetics have not been defined.. We measured BNPsp and high-sensitivity cardiac troponin T (hs-cTnT) in a reference group of individuals without structural heart disease (n = 285) and determined the release kinetics of these biomarkers in patients (n = 29) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure allowing exact timing of onset of iatrogenic AMI. Blood samples were collected before TASH and at numerous preselected time points after TASH.. The reference median BNPsp concentration was 53.4 pmol/L [interquartile range (IQR) 47.0-61.0; 95th percentile 85.9 pmol/L; 99th percentile 116.3 pmol/L]. Baseline concentrations in patients undergoing TASH were higher than in the reference group [91.9 pmol/L (IQR 62.9-116.4); P < 0.0001]. BNPsp increased significantly, peaking at 15 min after induction of AMI [149.6 pmol/L (109.5-204.9) vs baseline; P = 0.004] and declining slowly thereafter, falling below the preprocedural value after 8 h (P = 0.014). hs-cTnT increased significantly 15 min after induction of AMI [26 ng/L (19-39) vs 18 ng/L (11-29); P = 0.001] and remained high at all later time points.. BNPsp concentrations increased immediately after AMI induction, providing early evidence of myocardial injury. The release kinetics of BNPsp differed from those of hs-cTnT. These findings provide information that should help in establishing the diagnostic value of BNPsp in the setting of early AMI.

Topics: Ablation Techniques; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Early Diagnosis; Female; Heart Septum; Humans; Male; Middle Aged; Myocardial Infarction; Myocytes, Cardiac; Natriuretic Peptide, Brain; Prognosis; Protein Sorting Signals; Reference Values; Troponin T

To distinguish hypertrophic cardiomyopathy (HCM) from hypertensive left ventricular hypertrophy (H-LVH) based on a morphological examination is often challenging. Growth differentiation factor 15 (GDF-15) is a novel diagnostic and prognostic biomarker for several cardiovascular diseases. In patients with LVH, GDF-15 promises to be a useful biomarker to distinguish between HCM and H-LVH. We evaluated 93 patients with H-LVH, 28 with HCM, and 28 disease control individuals. Serum GDF-15 concentrations were measured with an enzyme-linked immunosorbent assay. Circulating GDF-15 levels were significantly higher in patients with H-LVH than with HCM (P = 0.003). On the other hand, values for plasma B-type natriuretic peptide (BNP) levels were significantly lower in patients with H-LVH than with HCM (P = 0.004). Serum GDF-15 and plasma BNP levels positively correlated in patients with H-LVH but not with HCM. Multivariate logistic regression analysis revealed GDF-15 (odds ratio 12.06, confidence interval 1.85-78.77, P < 0.01) as an independent predictor of H-LVH among patients with LVH. In receiver-operating characteristic analysis, GDF-15 achieved an area under the curve of 0.70 for the identification of H-LVH. We found that GDF-15 might be a useful biomarker for discriminating HCM from H-LVH. Understanding serum GDF-15 values may have clinical utility for patients with LVH because the therapeutic strategies for treating HCM and H-LVH differ.

Topics: Aged; Area Under Curve; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Diagnosis, Differential; Female; Growth Differentiation Factor 15; Humans; Hypertension; Hypertrophy, Left Ventricular; Logistic Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Odds Ratio; Predictive Value of Tests; Prognosis; ROC Curve

We aimed to evaluate left atrium (LA) phasic functions and relation with N-terminal pro-B- type natriuretic peptide (NT-proBNP) levels and symptomatic states of the patients with hypertrophic cardiomyopathy (HCM).. Left atrial volume was calculated at end-systole (Vmax), end-diastole and pre-atrial contraction by echocardiography in 75 patients with HCM and 75 control subjects. Left atrial ejection fraction (LAEF), expansion index (LAEI), active emptying volume index (LAAEVI) and fraction (LAAEFr), passive emptying volume index (LAPEVI) and fraction (LAPEFr) were calculated. NT-proBNP levels were measured.. Left atrial active emptying volume (LAAEV) positively correlated with Vmax (r=0.343, p=0.003) up to a point, but then reached a plateau with larger LA volumes in HCM group. The LAAEFr was the only variable which was similiar between asymptomatic patients and controls, but was significantly decreased in symptomatic patients (p<0.05). NT-proBNP was correlated with LAEF (r=-0.32, p=0.005), LAEI (r=-0387, p=0.001), and LAAEFr (r=-0.25, p=0.035) but not related with LAPEFr (p=0.4). In receiver operating characteristic curve analysis an NT-proBNP cut-off value of 1415 pg/mL identified reduced LAEF with 87% specificity and 59% sensitivity [AUC=0.77 (95% CI: 0.65-0.89), p=0.004], a cut-off value of 820 pg/mL predicted impaired LAEI with 81% specificity ve 67% sensitivity [AUC=0.78 (95% CI: 0.66-0.9), p<0.001]; while a cut-off value of 1320 pg/mL predicted impaired LAAEFr with 76% specificity and 67% sensitivity [AUC=0.79 (95% CI: 0.68-0.91), p=0.02].. In HCM, LA phasic functions alter according to the Frank-Starling mechanism indicating occurrence of a secondary atrial myopathy. Impairment of LA booster pump function seems to be associated with appearance of symptoms and NT-proBNP levels predict the deterioration of LA reservoir and pump functions in HCM population.

Topics: Area Under Curve; Atrial Function, Left; Biomarkers; Cardiomyopathy, Hypertrophic; Case-Control Studies; Echocardiography; Humans; Natriuretic Peptide, Brain; Peptide Fragments; ROC Curve; Sensitivity and Specificity

Although B-type natriuretic peptide (BNP) and highly sensitive cardiac troponin T (cTnT) are useful for the evaluation of clinical features in various cardiovascular diseases, there are comparatively few data regarding the utility of these parameters in patients with hypertrophic obstructive cardiomyopathy (HOCM). The goal of this study was to assess the association between BNP, cTnT and clinical parameters in patients with HOCM.. Cross-sectional survey. The relationship between BNP, cTnT and clinical end points and echocardiographic data was investigated.. This study included 102 consecutive outpatients with HOCM who were clinically stable.. BNP was significantly associated with both maximum left ventricular (LV) wall thickness (r=0.28; p=0.003), and septal peak early transmitral filling velocity/peak early diastolic mitral annulus velocity (r=0.51; p=0.0001). No statistically significant associations were seen between cTnT and any echocardiographic parameters, but the presence of atrial fibrillation (AF) was associated with a high level of cTnT (p=0.01).. BNP is useful for monitoring clinical parameters and as a reflection of both LV systolic/diastolic function and increased LV pressure in patients with HOCM. A high level of serum cTnT is associated with the presence of AF.

Topics: Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Cross-Sectional Studies; Female; Humans; Male; Natriuretic Peptide, Brain; Prognosis; Sensitivity and Specificity; Troponin T

Hypertrophic cardiomyopathy (HCM) patients are more susceptible to suffer from heart failure with normal ejection fraction (HFNEF). Therefore, it is critical to evaluate the relationship between left ventricular filling pressure (LVFP) and HFNEF, even if a large proportion of HCM patients have normal LVFP at rest. The objective was to assess the correlation between exercise tissue Doppler imaging (TDI) and early HFNEF in HCM patients by treadmill exercise echocardiography combined with cardiopulmonary exercise test (CPET).. Twenty-seven non-obstructive HCM patients and 31 age- and gender-matched healthy volunteers were enrolled in this study. All subjects underwent treadmill exercise echocardiography combined with CPET. N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were analyzed before and after exercise.. Five HCM patients had normal LVFP at rest and increased after exercise. For this subgroup, the relationship between minute ventilation and carbon dioxide production (VE/VCO2 slope) and NT-proBNP levels were higher compared with controls and the subgroup with normal resting and stress LVFP, but was similar to the subgroup with elevated LVFP both at rest and after exercise.. Elevated LVFP after exercise suggested the occurrence of early HFNEF in patients with non-obstructive HCM.

Topics: Adult; Cardiomyopathy, Hypertrophic; Echocardiography, Doppler; Exercise Test; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Function, Left

Several mutations in αB-crystallin (CryAB), a heat shock protein with chaperone-like activities, are causally linked to skeletal and cardiac myopathies in humans. To better understand the underlying pathogenic mechanisms, we had previously generated transgenic (TG) mice expressing R120GCryAB, which recapitulated distinguishing features of the myopathic disorder (e.g., protein aggregates, hypertrophic cardiomyopathy). To determine whether induced pluripotent stem cell (iPSC)-derived cardiomyocytes, a new experimental approach for human disease modeling, would be relevant to aggregation-prone disorders, we decided to exploit the existing transgenic mouse model to derive iPSCs from tail tip fibroblasts. Several iPSC lines were generated from TG and non-TG mice and validated for pluripotency. TG iPSC-derived cardiomyocytes contained perinuclear aggregates positive for CryAB staining, whereas CryAB protein accumulated in both detergent-soluble and insoluble fractions. iPSC-derived cardiomyocytes identified by cardiac troponin T staining were significantly larger when expressing R120GCryAB at a high level in comparison with TG low expressor or non-TG cells. Expression of fetal genes such as atrial natriuretic factor, B-type natriuretic peptide, and α-skeletal α-actin, assessed by quantitative reverse transcription-polymerase chain reaction, were increased in TG cardiomyocytes compared with non-TG, indicating the activation of the hypertrophic genetic program in vitro. Our study demonstrates for the first time that differentiation of R120G iPSCs into cardiomyocytes causes protein aggregation and cellular hypertrophy, recapitulating in vitro key pathognomonic hallmarks found in both animal models and patients. Our findings pave the way for further studies exploiting this cell model system for mechanistic and therapeutic investigations.

Topics: Actins; alpha-Crystallins; Animals; Atrial Natriuretic Factor; beta-Crystallins; Cardiomyopathy, Hypertrophic; Cell Differentiation; Cell Line; Gene Expression Regulation; Humans; Induced Pluripotent Stem Cells; Mice; Mice, Transgenic; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protein Multimerization; Reverse Transcriptase Polymerase Chain Reaction; Troponin T

To determine the relation between serum concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) and prognosis in patients with hypertrophic cardiomyopathy (HCM).. In total, 847 patients (53 ± 15 years; 67% male) with HCM (28% with left ventricular outflow tract obstruction ≥ 30 mmHg at rest) were followed for 3.5 years (IQR 2.5-4.5 years). The median NT-proBNP concentration was 78 pmol/L (range < 5-1817 pmol/L and IQR 31-183 pmol/L). Sixty-eight patients (8%) reached the primary endpoint of all-cause mortality or cardiac transplantation. NT-proBNP concentration predicted long-term survival from the primary endpoint [area under the receiver operating characteristic curve of 0.78 (95% confidence interval 0.73-0.84)]. A serum concentration of ≥ 135 pmol/L was associated with an annual event rate of 6.1% (95% CI 4.4-7.7). Three independent predictors of primary outcome were identified in a multivariable Cox model: New York Heart Association class III/IV (HR 2.10, 95% CI 1.21-3.65, P = 0.008), ejection fraction (HR 0.98, 95% CI 0.96-1.00, P = 0.035), log NT-proBNP (HR 2.04, 95% CI 1.56-2.66, P < 0.001). Log NT-proBNP was a significant predictor of heart failure (HF) and transplant-related deaths (n = 23; HR 3.03, 95% CI 1.99-4.60, P < 0.001) but not sudden death or appropriate implantable cardioverter defibrillator shock (n = 11; HR 1.54, 95% CI 0.91-2.60, P = 0.111). In patients with ejection fraction ≥ 50% (n = 673), log NT-proBNP remained an independent predictor of the primary outcome (HR 2.11, 95% CI 1.54-2.90, P < 0.001).. In patients with HCM, elevated NT-proBNP concentration is a strong predictor of overall prognosis, particularly HF-related death and transplantation.

Topics: Adolescent; Adult; Aged; Cardiomyopathy, Hypertrophic; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Prospective Studies; Young Adult

B-type natriuretic peptide is a conventional cardiac biomarker in adult cardiology, however, it is not commonly used in pediatric cases.. After introducing B-type natriuretic peptide measurements in pediatric patients for the evaluation of systemic right ventricular function, the authors wanted to evaluate the value of plasma B-type natriuretic peptide and compare the results with systolic and diastolic myocardial parameters obtained with conventional echocardiography and tissue Doppler imaging in children with cardiomyopathy.. Between 2007 and 2010, 58 plasma B-type natriuretic peptide measurements were performed in 32 children (dilated cardiomyopathy in 20, hypertrophic cardiomyopathy in 10 and non-compacted cardiomyopathy in 2 cases). The age of the patients was 7.9±6.6 years (mean±SD). Plasma B-type natriuretic peptide was measured using an electrochemiluminescent assay within one day from echocardiographic evaluation.. As compared to normal values, children with the 3 types of cardiomyopathies showed significant differences in plasma B-type natriutretic peptide levels (dilated cardiomyopathy vs normal, p<0.001; hypertrophic cardiomyopathy vs. normal, p<0.01; non-compacted cardiomyopathy vs. normal, p<0.001). There was a significant negative correlation (r = -0,63; p<0,01) between B-type natriuretic peptide levels (range, 12-7002 ng/L; mean±SD, 1531±1750 ng/L) and linEF values (range, 4-50%; mean±SD, 22.5±13%). For B-type natriuteric peptide, a cut-off point of 1000 ng/L proved to differentiate significantly decreased linEF values (<17%). B-type natriuretic peptide levels significantly correlated with left ventricular end-diastolic diameter (r = 0.899; p<0.001), with left ventricular anular S wave parameters (r = 0.689; p<0.001) and with E/e ratio (r = 0.43; p<0.05).. B-type natriuretic peptide measurements are recommended in all types of cardiomyopathies.

Topics: Adolescent; Biomarkers; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Echocardiography; Echocardiography, Doppler; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Young Adult

The aim of this study was to determine the relationship between B-type natriuretic peptide (BNP) and survival in patients with hypertrophic cardiomyopathy.. Natriuretic peptides are released in response to neurohormonal activation, myocardial stretch, and wall tension and therefore reflect hemodynamic derangements.. A total of 772 patients with hypertrophic cardiomyopathy had BNP obtained in conjunction with echocardiography and clinical evaluation, inclusive of cardiopulmonary exercise evaluation in 429 patients (56%).. Survival free of all-cause mortality was lower across increasing levels of BNP (log-rank test, p = 0.002). Three-year survival by tertile was 99.2% (95% confidence interval: 94.3% to 99.9%; BNP level ≤98 pg/ml), 94.8% (95% confidence interval: 88.2% to 97.8%; BNP level, >98 to <298 pg/ml), and 89.9% (95% confidence interval: 82.0% to 94.5%; BNP level ≥298 pg/ml). Compared with patients in the first tertile, the hazard ratios for death in the second and third tertiles were 4.88 (p = 0.006) and 6.98 (p = 0.0003), respectively. This relationship persisted in patients without resting obstructive physiology (n = 497, p = 0.01). BNP levels were related to New York Heart Association functional status (p < 0.0001) and the subsequent need for septal reduction therapy in follow-up (p = 0.04).. In this large cohort of patients with hypertrophic cardiomyopathy, BNP was an independent predictor of morbidity and mortality.

Topics: Adult; Aged; Cardiomyopathy, Hypertrophic; Cohort Studies; Disease-Free Survival; Echocardiography; Female; Gene Expression Regulation; Humans; Immunoassay; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Proportional Hazards Models; Regression Analysis; Time Factors; Treatment Outcome

Myocardial fibrosis assessed by late gadolinium enhancement cardiac magnetic resonance imaging is associated with cardiovascular events in patients with hypertrophic cardiomyopathy (HC), but few data are available regarding the utility of biomarkers for detecting late gadolinium enhancement. The aim of this study was to examine serum levels of myoglobin, cardiac myosin light chain I, high-sensitivity cardiac troponin T (hs-cTnT), and creatine kinase-MB isoenzyme and plasma levels of brain natriuretic peptide (BNP) in relation to late gadolinium enhancement in 53 patients with HC. Levels of hs-cTnT and BNP were higher in 23 patients with late gadolinium enhancement than in 30 patients without it (p <0.01 for both). An hs-cTnT level ≥0.007 ng/ml or a BNP level ≥70 pg/ml had good diagnostic value for detecting late gadolinium enhancement, with sensitivity of 96% or specificity of 90% with the combination of these 2 biomarkers. The extent of late gadolinium enhancement was correlated with BNP level (p <0.01) but not with hs-cTnT level in 23 patients with HC with late gadolinium enhancement. The increase in the extent of late gadolinium enhancement was related to hs-cTnT level in 8 patients during 22 months of follow-up (p = 0.02). In conclusion, the combination of hs-cTnT and BNP is useful in detecting myocardial fibrosis in patients with HC. The findings of this study indicate that hs-cTnT is a direct marker of ongoing myocardial fibrosis and that BNP is a marker of left ventricular overload partially associated with myocardial fibrosis.

Topics: Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Female; Fibrosis; Follow-Up Studies; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Troponin T

Previous studies have shown that tissue Doppler imaging (TDI) is able to identify mutation carriers of hypertrophic cardiomyopathy (HC) before the development of the clinical phenotype. However, data are scarce and have sometimes been controversial. We performed a systematic study that included conventional echocardiography, TDI, and plasma NT-probrain natriuretic peptide (NT-proBNP) measurement to evaluate the parameters that could identify HC mutation carriers. A total of 138 genotyped subjects were included and divided into 3 groups: group 1, those with HC (n = 62); group 2, mutation carriers (first-degree relatives with a positive genotype but negative phenotype; n = 34); and group 3, controls (first-degree relatives with a negative genotype and phenotype; n = 42). An echocardiographic study, including TDI, was performed on all subjects, and a TDI-derived index (global function index) was also determined. The age-adjusted mean differences in the echocardiographic and TDI parameters and NT-proBNP levels were compared among the 3 groups. Compared with the HC group, the carriers had significantly higher mean E' velocities, lower mean E/E' ratio, higher mean S' velocities, and lower mean global function index and NT-proBNP values. The carriers and controls did not differ significantly either in the echocardiographic parameters studied or in the NT-proBNP levels. In conclusion, the echocardiographic and TDI parameters and NT-proBNP levels cannot be used to identify the HC mutation carrier state and therefore do not appear to be reliable for the purpose of making a preclinical diagnosis of the disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Echocardiography, Doppler; Female; Genotype; Heterozygote; Humans; Male; Middle Aged; Mutation; Myosins; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Troponin; Young Adult

In hypertrophic cardiomyopathy, the plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) correlate with functional capacity. However, their prognostic relevance remains unresolved. We followed up 183 stable outpatients with hypertrophic cardiomyopathy (age 50 ± 17 years, 64% men) for 3.9 ± 2.8 years after NT-proBNP measurement. The primary end point included cardiovascular death, heart transplantation, resuscitated cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. The secondary end point (SE) included heart failure-related death or hospitalization, progression to end-stage disease, and stroke. The median NT-proBNP level was 615 pg/ml (intertertile range 310 to 1,025). The incidence of the primary end point in the lower, middle, and upper tertiles was 0%, 1.3%, and 2.1% annually, respectively (overall p = 0.01). On multivariate analysis, the only independent predictors of the primary end point were NT-proBNP (hazard ratio for log-transformed values 5.8, 95% confidence interval 1.07 to 31.6; p = 0.04) and a restrictive left ventricular filling pattern (hazard ratio 5.19, 95% confidence interval 1.3 to 21.9; p = 0.02). The NT-proBNP cutoff value of 810 pg/ml had the best sensitivity for the primary end point (88%), but the specificity was low (61%). The incidence of the SE in the lower, middle, and upper NT-proBNP tertiles was 4.6%, 12.0%, and 11.2% annually, respectively (overall p = 0.001). An NT-proBNP level of <310 pg/ml was associated with a 75% reduction in the rate of SE compared with a level of ≥310 pg/ml (hazard ratio 0.25, 95% confidence interval 0.11 to 0.57; p = 0.001), independent of age, left ventricular outflow tract obstruction, or atrial fibrillation. In conclusion, in stable outpatients with hypertrophic cardiomyopathy, plasma NT-proBNP proved a powerful independent predictor of death and heart failure-related events. Although the positive predictive accuracy of an elevated NT-proBNP level was modest, low values reflected true clinical stability, suggesting the possibility of avoiding or postponing aggressive treatment options.

Topics: Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography; Electrocardiography; Female; Heart Ventricles; Humans; Italy; Male; Middle Aged; Natriuretic Peptide, Brain; Outpatients; Peptide Fragments; Prognosis; Protein Precursors; Retrospective Studies; Stroke Volume; Survival Rate

Left ventricular hypertrophy (LVH) with intraventricular septum thickness (IVST) between 1.2 and 1.5 cm in athletes represents a "gray zone" between physiologic adaptation and mild hypertrophic cardiomyopathy (HCM). Various echo and laboratory parameters have been reported till now in the literature to discriminate the "gray zone" entities. Aim of this study was to assess the efficacy of these "classic" parameters in differentiating physiologic LVH in athletes from mild HCM in a highly selected population. Nine highly trained athletes with IVST (1.28 ± 0.07 cm), 9 patients with mild HCM (1.38 ± 0.11 cm), and 26 athletes without LVH (1.06 ± 0.09 cm; P < 0.0005) underwent echocardiographic study, cardiopulmonary treadmill exercise stress test, and brain natriuretic peptide (BNP) measurement before and after exercise. Among all parameters tested, 7 were found to significantly differ between "gray zone" groups. After bootstrapping analysis, it was found that athletes with left ventricular end-diastolic diameter <4.74 cm, mitral deceleration time >200 ms, isovolumic relaxation time >94 ms, tricuspid E/A < 1.63, septum Em < 9.5 cm/sec, relative wall thickness >0.445, and a BNP value at rest >9.84 pg/mL had a greater possibility for having underlying cardiomyopathy. A 10-point score based on these parameters showed accuracy (area under the curve = 0.958 [95%CI: 0.738-1.0; P = 0.00005, standard error = 0.0342]) for revealing HCM in a gray zone athletic population. Differentiation of adaptive LVH versus HCM in a gray zone population could be facilitated by recognition of certain features referring to LV dimensions, diastolic function, and BNP.

Topics: Adolescent; Adult; Athletes; Cardiomegaly, Exercise-Induced; Cardiomyopathy, Hypertrophic; Diagnosis, Differential; Echocardiography; Exercise Test; Follow-Up Studies; Heart Ventricles; Humans; Hypertrophy, Left Ventricular; Male; Natriuretic Peptide, Brain; Pilot Projects; Retrospective Studies; Young Adult

Whether the left ventricular (LV) mass index (LVMI) and LV volumetric parameters are associated independently with natriuretic peptide levels is unclear in hypertrophic cardiomyopathy (HCM). Therefore, we investigated which parameters have an independent relationship with N-terminal pro-B type natriuretic peptide (NT-proBNP) levels in HCM patients using echocardiography and cardiac magnetic resonance imaging (CMR). A total of 103 patients with HCM (82 men, age 53 ± 12 years) were evaluated. Echocardiographic evaluations included left atrial volume index (LAVI) and early diastolic mitral inflow E velocity to early annular Ea velocity ratio (E/Ea). LVMI, maximal wall thickness and LV volumetric parameters were measured using CMR. The median value of NT-proBNP level was 387.0 pg/ml. The mean NT-proBNP level in patients with non-apical HCM (n = 69; 36 patients with asymmetric septal hypertrophy, 11 with diffuse, and 22 with mixed type) was significantly higher than in those with apical HCM (n = 34, P < 0.001). NT-proBNP level was negatively correlated with LV end-diastolic volume (LVEDV) (r = -0.263, P = 0.007) and positively with LVMI (r = 0.225, P = 0.022) and maximal wall thickness (r = 0.495, P < 0.001). Among the echocardiographic variables, LAVI (r = 0.492, P < 0.001) and E/Ea (r = 0.432, P < 0.001) were correlated with NT-proBNP. On multivariable analysis, non-apical HCM, increased maximal wall thickness and LAVI were independently related with NT-proBNP. Severity of LV hypertrophy and diastolic parameters might be important in the elevation of NT-proBNP level in HCM. Therefore, further evaluation of these parameters in HCM might be warranted.

Topics: Adult; Aged; Atrial Function, Left; Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography, Doppler; Female; Humans; Hypertrophy, Left Ventricular; Linear Models; Magnetic Resonance Imaging; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Observer Variation; Peptide Fragments; Predictive Value of Tests; Reproducibility of Results; Republic of Korea; Risk Assessment; Risk Factors; Severity of Illness Index; Stroke Volume; Up-Regulation; Ventricular Function, Left

Doxorubicin [(DOX) Adriamycin] is an effective anticancer agent whose major limiting side effect is cardiotoxicity. This cardiotoxicity is predicted only by the cumulative dose of DOX where the clinical situation involves chronic drug administration. Therefore, we investigate the effect of chronic DOX cardiotoxicity on expression of the cardiac cytochrome P450 (P450) enzymes and arachidonic acid (AA) metabolism in male Sprague-Dawley (SD) rats. The chronic toxicity was induced by multiple intraperitoneal injections for a cumulative dose of 15 mg/kg divided into six injections within 2 weeks. After 14 days of the last injection, the heart, liver, and kidney were harvested, and the expression of different genes was determined by real-time polymerase chain reaction. In addition, microsomal protein from the heart was prepared and incubated with AA. Thereafter, different AA metabolites were analyzed by liquid chromatography-electrospray ionization-mass spectrometry. The chronic DOX cardiotoxicity significantly induced gene expression of hypertrophic markers, apoptotic markers, CYP2E1, CYP4A3, CYP4F1, CYP4F5, and soluble epoxide hydrolase (sEH) enzyme, which was accompanied by an increase in the activity of P450 ω-hydroxylases and sEH. In addition, both the sEH inhibitor, trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid, and the ω-hydroxylase inhibitor, N-hydroxy-N'-(4-butyl-2-methylphenyl)-formamidine (HET0016), significantly prevented the DOX-mediated induction of the hypertrophic markers in the cardiac-derived H9c2 cells, which further confirms the role of these enzymes in DOX cardiotoxicity. Furthermore, gene expression of P450 and sEH was altered in an organ-specific manner. As a result, the chronic DOX administration leads to an imbalance between P450-mediated cardiotoxic and cardioprotective pathways. Therefore, P450 ω-hydroxylases and sEH might be considered as novel targets to prevent and/or treat DOX cardiotoxicity.

Topics: Animals; Apoptosis; Arachidonic Acid; Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Hypertrophic; Cells, Cultured; Cytochrome P-450 CYP4A; Cytochrome P-450 Enzyme System; Doxorubicin; Epoxide Hydrolases; Gene Expression; Heart; Inflammation; Kidney; Liver; Male; Microsomes; Myocardium; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; RNA, Messenger

Although serum cardiac troponin I (cTnI) and plasma brain natriuretic peptide (BNP) have become clinically important tools as diagnostic and prognostic markers for ischemic heart disease and heart failure, the usefulness of these biomarkers for risk stratification of hypertrophic cardiomyopathy (HCM) is not clear.. We studied 167 patients with HCM, and cTnI and BNP were measured. During follow-up (38.5 months), 20 patients suffered from cardiovascular events: HCM-related deaths in 6, hospitalization for heart failure in 8, embolic stroke in 5 and 1 patient with spontaneous sustained ventricular tachycardia. Patients with high cTnI values (≥0.04 ng/ml) had more frequent cardiovascular events than did those with low cTnI values (P=0.008). Similarly, there were more frequent adverse events in the high BNP group (≥200 pg/ml) than in the low BNP group (P=0.002). When groups were allocated according to both cTnI and BNP measurements, serum cTnI used in conjunction with BNP further improved the prognostic value; patients with both high cTnI and BNP values had an 11.7-fold increased risk of cardiovascular events compared with those with both low cTnI and BNP values.. CTnI and BNP are useful parameters for identifying patients at risk for clinical deteriorations, and combined measurements of these biomarkers further improves the prognostic value of increased cardiovascular events in HCM.

Topics: Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Embolism; Female; Follow-Up Studies; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Stroke; Tachycardia, Ventricular; Troponin I

Persistent controversy underlies the functional roles of specific p38 MAPK isoforms in cardiac biology and regulation of hypertrophy-associated genes. Here we show that adenoviral gene transfer of p38β but not p38α increased B-type natriuretic peptide (BNP) mRNA levels in vitro as well as atrial natriuretic peptide mRNA levels both in vitro and in vivo. Overexpression of p38α, in turn, augmented the expression fibrosis-related genes connective tissue growth factor, basic fibroblast growth factor and matrix metalloproteinase-9 both in vitro and in vivo. p38β-induced BNP transcription was diminished by mutation of GATA-4 binding site, whereas overexpression of MKK6b, an upstream regulator of p38α and p38β, activated BNP transcription through both GATA-4 and AP-1. Overexpression of MKK3, upstream regulator of p38α, induced BNP transcription independently from AP-1 and GATA-4. These data provide new evidence for diversity in downstream targets and functional roles of p38 pathway kinases in regulation of hypertrophy-associated cardiac genes.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cell Death; Cells, Cultured; Connective Tissue Growth Factor; Fibroblast Growth Factor 2; GATA4 Transcription Factor; Gene Expression Regulation; Imidazoles; Isoenzymes; Matrix Metalloproteinase 9; Mitogen-Activated Protein Kinase Kinases; Myocytes, Cardiac; Natriuretic Peptide, Brain; p38 Mitogen-Activated Protein Kinases; Promoter Regions, Genetic; Pyridines; Rats; Signal Transduction; Transcription, Genetic; Transcriptional Activation

Cats with hypertrophic cardiomyopathy (HCM) often have no clinical signs or subtle signs. Measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP) has been demonstrated in people to be highly specific for heart disease and also correlates with severity of HCM. NT-proBNP may also be valuable in detecting and grading HCM in cats, but results to date have been equivocal.. The aims of this study were to evaluate NT-proBNP as a screening test for diagnosis of HCM in cats and determine an appropriate cut-off value and to determine if NT-proBNP concentrations correlated with severity of HCM in cats.. Plasma NT-proBNP concentrations were measured in 201 cats using an ELISA designed for use in cats. Cats were classified using echocardiography as clinically healthy controls (n=99) or cats with equivocal (n=9), mild (n=15), moderate (n=17), or severe (n=61) HCM.. NT-proBNP concentrations (median; 25th-75th interquartile percentiles) in mildly (216.1; 87.6-392.5 pmol/L), moderately (282.7; 131.9-466.6 pmol/L), and severely (839.5; 655.3-1046.4 pmol/L) affected cats were significantly higher than those in healthy controls (18.9; 3.4-62.4 pmol/L). Concentrations in severely affected cats were significantly higher than in cats from other HCM groups. There was no significant difference between mild and moderate HCM. Cut-off values >49 pmol/L had a sensitivity of 97.8% and specificity of 66.7%; >100 pmol/L had a sensitivity of 92.4% and specificity of 93.9%; and >150 pmol/L had a sensitivity of 88% and a specificity of 100%.. NT-proBNP with a cut-off value of >100 pmol/L was useful in detecting even mild HCM. Cats with increased NT-proBNP concentrations should be examined by echocardiography.

Topics: Animals; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Echocardiography; Enzyme-Linked Immunosorbent Assay; Female; Male; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Severity of Illness Index

In addition to sudden death, heart failure and stroke due to atrial fibrillation are important in patients with hypertrophic cardiomyopathy (HCM). The aim of the present study was to determine whether Doppler tissue imaging findings and plasma B-type natriuretic peptide (BNP) levels, which are widely used for risk stratification in several cardiovascular diseases, are useful for risk stratification in patients with HCM in a regional cohort.. One hundred thirty patients (82 men; mean age, 60 ± 16 years) with HCM were enrolled in this study.. Twenty end points were observed during a mean follow-up period of 3.7 ± 1.7 years. Septal E/e' ratios and BNP levels in patients with events were higher than those in patients without events (17.4 ± 6.3 vs 10.6 ± 4.3, P < .0001, and 441 ± 304 vs 202 ± 174 pg/mL, P < .0001, respectively). By multivariate logistic regression analysis, a high septal E/e' ratio, in addition to a history of syncope and documentation of atrial fibrillation, was a significant predictor of combined end points. In contrast, plasma BNP levels were not a significant predictor of combined end points.. Assessment by Doppler tissue imaging is useful for further risk stratification of patients with HCM.

Topics: Cardiomyopathy, Hypertrophic; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Immunoenzyme Techniques; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prognosis; Prospective Studies; Stroke Volume; Ventricular Function, Left

Nonsustained ventricular tachycardia (nVT) may have ominous implications for patients with hypertrophic cardiomyopathy (HCM). The microvolt T-wave alternans (TWA) has been proposed as a noninvasive tool-identifying patients at risk of sudden cardiac death and ventricular tachycardia/fibrillation (VT/VF). The aim of the study was to determine the significance of TWA in predicting nVT episodes and compare how other electrocardiographic parameters can predict the occurrence of nVT.. The study group consisted of 88 patients with HCM. TWA was assessed during exercise test using the CH2000 system. All patients underwent Holter monitoring (HM) within 2-4 weeks before TWA test (preexercise HM1) and immediately after (postexercise HM2). During HM, we analyzed: arrhythmias, QT intervals, the presence of late ventricular potentials (LP), heart rate variability, heart rate turbulence.. Depending on TWA results, the patients were divided into two groups: TWA+; 46 patients (52.3%) with positive/indeterminate results, and TWA-; 42 patients (47.7%) with negative results. The nVT episodes were more frequent among TWA(+) both in HM1 and HM2. The presence of TWA increases the risk of postexercise nVT over twenty times (OR = 21.03). Moreover, in HM1, QTc and LP, and in HM2, again QTc and N-terminal precursor of brain natriuretic peptide proved to be significant predictors of nVT. The addition of TWA to the models did not improve the arrhythmia risk assessment.. Repolarization abnormality plays an important role in generating nVT in patients with HCM, but TWA does not specifically predict the risk of arrhythmic end point.

Topics: Algorithms; Biomarkers; Cardiomyopathy, Hypertrophic; Chi-Square Distribution; Echocardiography, Doppler; Electrocardiography, Ambulatory; Exercise Test; Female; Heart Conduction System; Heart Rate; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prevalence; Prognosis; ROC Curve; Sensitivity and Specificity; Statistics, Nonparametric

Serum cardiac troponin I (cTnI) is a sensitive and specific marker of myocardial injury. However, a systematic evaluation of cTnI in hypertrophic cardiomyopathy (HCM) patients has not been performed.. The purpose of this study is to evaluate cTnI and determine its relationship to clinical features in HCM.. We studied serum cTnI in 162 consecutive HCM patients.. Serum cTnI ranged from 0.01 to 0.83 ng/mL (mean, 0.068 +/- 0.100 ng/mL) and was higher in male patients (P < .001), those with atrial fibrillation (P = .033), and left ventricular (LV) systolic dysfunction (P = .046). Serum cTnI values were also correlated with maximum LV wall thickness (r = 0.30, P < .001), LV end-systolic diameter (r = 0.20, P = .012), and E/Ea (peak early transmitral filling velocity/early diastolic mitral annulus velocity; r = 0.24, P = .004). Serum cTnI levels were not significantly different among New York Heart Association (NYHA) functional class and there was no difference between patients with or without LV outflow tract obstruction; although B-type natriuretic peptide (BNP) levels showed significant difference in those variables. Serum cTnI had very weak correlation with BNP values (r = 0.18, P = .023). Multivariate analysis revealed an independent relationship between cTnI and maximum LV wall thickness, E/Ea, and male gender.. In patients with HCM, serum cTnI was associated with important clinical indices such as maximum LV wall thickness, LV dysfunction, and male gender. Serum cTnI seemed to have clinical significance different from that of BNP and may not be reflecting cardiac load but the LV remodeling process in HCM.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathy, Hypertrophic; Chi-Square Distribution; Child; Cross-Sectional Studies; Echocardiography, Doppler; Female; Hemodynamics; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Regression Analysis; Sex Factors; Troponin I; Up-Regulation; Ventricular Dysfunction, Left; Ventricular Function, Left; Ventricular Remodeling; Young Adult

Myocardial infarct (MI) size is a well-established prognostic marker but the association of serum markers with MI size, as measured by myocardial perfusion imaging (MPI), has not been well studied in patients with hypertrophic cardiomyopathy (HC) after alcohol septal ablation (ASA). Creatine kinase (CK), CK-MB, troponin I, and brain natriuretic peptide were measured before and at multiple points after ASA in patients with HC and were correlated with MI size measured by MPI. MPI at rest was performed in 54 patients with HC at a median of 2 days after ASA. CK, CK-MB, and troponin I increased after ASA to peak levels at 12 hours and their cumulative levels (area under the curve) showed significant correlation with size of MI by MPI (r = 0.544, 0.408, and 0.477, p <0.001, 0.003, and 0.001, respectively). The best marker was level of CK at 12 hours (r = 0.609, p <0.0001) after ASA. Brain natriuretic peptide level did not change significantly after ASA (p = 1.0) and only weakly correlated with MI size by MPI (r = 0.130, p = 0.007). In conclusion, CK, CK-MB, and troponin I measured at 12 hours, at peak, and as the area under the curve correlated well with infarct size, but CK level at 12 hours was the best marker. CK continues to be a useful marker of MI size despite the introduction of newer, more specific markers, especially when infarct onset is known with certainty as in patients with HC undergoing ASA.

Topics: Ablation Techniques; Adult; Aged; Biomarkers; Cardiac-Gated Single-Photon Emission Computer-Assisted Tomography; Cardiomyopathy, Hypertrophic; Cohort Studies; Creatine Kinase, MB Form; Ethanol; Female; Humans; Male; Middle Aged; Myocardial Infarction; Myocardial Perfusion Imaging; Natriuretic Peptide, Brain; Predictive Value of Tests; Retrospective Studies; Solvents; Troponin I

Adiponectin, which is an adipose-derived protein with antiatherosclerogenic activities, has been reported to be elevated in patients with heart failure. However, there are no reports on the significance of adiponectin in patients with hypertrophic cardiomyopathy (HCM). The purpose of this study was to elucidate the clinical significance of plasma adiponectin levels in HCM patients. Clinical characteristics, echocardiographic parameters, and levels of plasma B-type natriuretic peptide (BNP) and adiponectin were evaluated in 106 HCM patients. The plasma adiponectin levels were 10.8 +/- 6.3 (range, 2.7-37.3) microg/mL. Plasma adiponectin levels were positively related to age and inversely related to body mass index (BMI). Among echocardiographic parameters, % fractional shortening (r = -0.20, P = 0.03) and maximum LV wall thickness (r = -0.23, P = 0.02) were inversely related to plasma adiponectin levels. A significant correlation between plasma adiponectin levels and BNP levels was also observed (r = 0.27, P = 0.005). In multivariate analysis, BMI, % fractional shortening, and plasma BNP levels were independent predictors of plasma adiponectin levels. Plasma adiponectin levels are associated with impaired LV systolic function in HCM patients, but not with the LV outflow gradient. Together with BNP, adiponectin can be a useful biomarker for assessing disease severity in HCM patients.

Topics: Adiponectin; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Diastole; Echocardiography; Female; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Ventricular Function, Left; Ventricular Remodeling

The role of brain natriuretic peptide (BNP) in differentiating the athlete's heart from maladaptive cardiac hypertrophy is unclear.. To address this issue, an integrated M mode, two-dimensional B mode and Doppler echocardiographical study were performed and plasma BNP levels were measured in 25 strength athletes, 25 patients with established hypertrophic cardiomyopathy (HCM) and 25 healthy volunteers.. Among athletes, BNP levels correlated negatively with the total training time (r = -0.79, p = 0.002) and positively with ejection fraction (r = 0.58, p = 0.049) and fractional shortening (r = 0.57, p = 0.049). A BNP cut-off value of 11.8 pg/ml had 88% specificity and 74% negative predictive value for the exclusion of HCM.. Brain natriuretic peptide might be useful as a preparticipation screening test in athletes.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography; Humans; Male; Natriuretic Peptide, Brain; Pilot Projects; Sports; Young Adult

The purpose of this study was to evaluate the value of measuring plasma NT-proBNP concentration as a screening tool in cats with varying severity of subclinical hypertrophic cardiomyopathy (HCM). Plasma NT-proBNP concentration was measured in 35 cats that had previously been classified as normal, equivocal, moderate HCM or severe HCM via echocardiography. No cat had ever been in congestive heart failure. Cats with severe HCM had a significantly higher NT-proBNP concentration compared to the other groups (P<0.0003), however, the sensitivity of NT-proBNP for diagnosing cats with severe disease was only 44% (cutoff≤100pmol/l) to 55% (cutoff≤40pmol/l). There was no significant difference in NT-proBNP concentration between normal, equivocal and moderate categories (sensitivity for detecting moderate HCM was 0%). Based on the results of this study, NT-proBNP concentration is not considered adequate as a screening test for detecting mild to moderate HCM in Maine Coon cats and it appears that it may miss many cats with severe HCM.

Topics: Animals; Biomarkers; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Female; Male; Mass Screening; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Severity of Illness Index

Distinguishing physiological hypertrophy from hypertrophic cardiomyopathy in athletes remains difficult, but vital in view of the risk of sudden death under effort. NT-proBNP was previously reported to be usually normal in healthy athletes, but often elevated in case of hypertrophic cardiomyopathy.. To assess the interest of NT-proBNP in differential diagnosis of left ventricular hypertrophy in athletes.. NT-proBNP levels were measured at rest and after effort in trained athletes referred for suspectedly abnormal (>or=13 mm) left ventricular hypertrophy.. 17 patients were included, 10 of whom were diagnosed with hypertrophic cardiomyopathy (group I) while the other 7 presented typical signs of athlete's heart (group II). NT-proBNP levels did not significantly differ between groups, whether at rest or after effort. NT-proBNP levels were, however, significantly elevated in 3 subjects in group I, while being consistently normal in group II.. In active athletes presenting with ambiguous left ventricular hypertrophy, abnormal NT-proBNP levels indicate hypertrophic cardiomyopathy, whereas normal values are inconclusive.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Sports; Young Adult

We describe a 16-year-old suffering from the dilated phase of mid-ventricular obstructive hypertrophic cardiomyopathy with end-stage heart failure. Her plasma type-B natriuretic peptide level exceeded 8000 pg/ml, and she refused heart transplantation. She underwent an apicoaortic valved conduit as an alternative to the heart transplant procedure. This traditional procedure is still an ideal operation for very sick cardiomyopathy patients to avoid or delay heart transplantation.

Topics: Adolescent; Biomarkers; Cardiac Surgical Procedures; Cardiomyopathy, Hypertrophic; Echocardiography; Female; Heart Failure; Heart Transplantation; Humans; Natriuretic Peptide, Brain; Noonan Syndrome; Tomography, X-Ray Computed; Treatment Outcome; Up-Regulation

The purpose of this study was to explore the relationship between plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and extensive echocardiographic variables in patients with hypertrophic cardiomyopathy (HCM).. We evaluated plasma NT-proBNP levels in 88 patients with HCM and examined the plasma NT-proBNP levels' relationships with echocardiographic indexes. Echocardiographic variables were analysed using univariate and multivariate logistic regression to identify predictors of NT-proBNP elevation.. Several echocardiographic variables predicted NT-proBNP elevation, including left atrial dimension index (LADI), left ventricular maximal wall thickness (MWT), left ventricular posterior wall thickness, severe mitral regurgitation, mitral septal and lateral tissue Doppler velocities, and mitral septal E/Ea ratio. Left ventricular ejection fraction, left ventricular dimensions, mitral early flow propagation velocity, isovolumic relaxation time, and left ventricular outflow tract obstruction were not significant predictors of NT-proBNP in this group of patients. With multivariate analysis LADI (HR 5.0; 95% CI 1.5-17.1, p=0.01) and MWT (HR 4.0; 95% CI 1.2-13.2, p=0.022) emerged as independent determinants of NT-proBNP elevation.. In HCM plasma NT-proBNP is prominently increased. LADI and MWT are independent predictors of elevated levels. These data indicate that NT-proBNP elevations are mainly determined by diastolic load in HCM.

Topics: Adult; Cardiomyopathy, Hypertrophic; Cohort Studies; Echocardiography, Doppler; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Ventricular Dysfunction, Left

Topics: Athletes; Cardiomyopathy, Hypertrophic; Diagnosis, Differential; Gadolinium; Humans; Hypertrophy, Left Ventricular; Magnetic Resonance Imaging; Natriuretic Peptide, Brain

To evaluate the utility of feline NT-proBNP plasma concentration [NT-proBNP] as a screening tool for cats with subclinical hypertrophic cardiomyopathy (HCM).. Forty adult Maine Coon or Maine Coon crossbred cats from the feline HCM research colony at the University of California, Davis were studied. All cats had previously been genotyped as heterozygous or negative for the A31P myosin binding protein C (MYBPC) mutation. Echocardiograms were performed to assess the severity of HCM in each cat. Blood samples were collected for evaluation of [NT-proBNP].. In these cats with severe HCM, [NT-proBNP] was significantly elevated (P<0.0001) when compared to all other groups of cats and an [NT-proBNP]>44pmol/L accurately predicted the presence of severe HCM. However, [NT-proBNP] was not increased in cats with moderate or equivocal HCM when compared to normal cats. Cats heterozygous for the MYBPC mutation had a significantly elevated [NT-proBNP] when compared to cats without the A31P mutation (P=0.028).. Measurement of [NT-proBNP] has a high sensitivity and specificity as a means of detecting severe HCM in cats, but it is not sensitive for the identification of moderate HCM as judged by the evaluation of Maine Coon and Maine Coon cross cats in our colony. Consequently, we conclude that this test cannot be used to screen cats for the presence of mild to moderate HCM.

Topics: Animals; Biomarkers; Cardiomyopathy, Hypertrophic; Carrier Proteins; Case-Control Studies; Cat Diseases; Cats; Echocardiography; Female; Male; Mass Screening; Mutation; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Sensitivity and Specificity; Severity of Illness Index

Recent reports suggest that left ventricular diastolic function assessed by tissue Doppler imaging (TDI) and plasma B-type natriuretic peptide (BNP) levels can relate to functional status in patients with hypertrophic cardiomyopathy (HCM). However, it is unclear which is more useful to predict the exercise capacity in HCM patients without systolic impairment and/or atrial fibrillation, TDI or BNP levels.. The present study directly compared the clinical relevance of assessing diastolic function using TDI and measuring the plasma BNP level in patients with HCM.. We evaluated diastolic function using TDI as well as plasma BNP levels in 31 patients (52.2+/-16.9 years of age; 20 males) with HCM and examined the relationship of these values to exercise capacity (peak O(2) consumption (VO(2))) measured by cardiopulmonary exercise tests.. Average peak VO(2) was 18.5+/-4.7 ml/(kg min). Although the E/A ratio by transmitral flow was not correlated with peak VO(2), the lateral E/E(a) ratio assessed by TDI was significantly correlated with peak VO(2) (r=-0.52, p=0.003). On the other hand, plasma BNP level was not significantly related to peak VO(2) but NYHA class.. Assessment of diastolic function using TDI, not plasma BNP levels, is more useful for predicting objective exercise capacity in HCM patients without systolic impairment and/or atrial fibrillation.

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography, Doppler; Exercise Tolerance; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests

Left atrial remodelling, assessed as left atrial volume (LAV), has been proposed as a good marker of left ventricular diastolic dysfunction. The aim of this study was to analyse the influence of LAV on exercise performance in hypertrophic cardiomyopathy (HCM), and in a subset of subjects, assess the relation of LAV and exercise performance to four biomarkers of disease pathophysiology: matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) (as indices of tissue remodelling), N-terminal portion of pro B-type natriuretic peptide (NT-pro-BNP) (associated with ventricular dysfunction) and C-reactive protein (CRP, an index of inflammation).. We studied 75 consecutive HCM patients (aged 46 +/- 14 years, 56 men) where LAV was calculated assuming the ellipsoid model with two orthogonal planes. LAV was indexed to body surface area. Exercise capacity was evaluated by treadmill exercise test (symptom limited) and assessed with metabolic equivalent units (MET). Basal NT-pro-BNP and CRP levels were measured in 70 patients, whereas MMP-2 and TIMP-1 in 43 patients.. Enlarged LAV was observed in those patients with previous atrial fibrillation (p = 0.016). Mean LAV was greater in patients with impaired functional New York Heart Association (NYHA) class (p < 0.001). LAV correlated with age (Spearman, r: 0.28), higher maximal left ventricular wall thickness (r: 0.32) and raised E/A ratio (r: 0.37) (all p < 0.01). LAV was significantly correlated with NT-pro-BNP values (r: 0.34; p = 0.04), MMP-2 (r: 0.32; p = 0.034), CRP (r: 0.33; p = 0.005) and correlated inversely with MET units (r: -0.39; p < 0.01). In multivariate analysis, MET units were only associated with NT-pro-BNP (p = 0.002) and LAV (p = 0.010).. Enlarged LAV is associated with impaired functional NYHA class and inversely with treadmill exercise capacity. Enlarged LAV is also associated with NT-pro-BNP, MMP-2 and CRP, perhaps as markers of disease severity and tissue remodelling. Age, LAV and NT-pro-BNP are independent predictors of exercise performance.

Topics: Adult; Atrial Fibrillation; Atrial Function, Left; Biomarkers; C-Reactive Protein; Cardiomyopathy, Hypertrophic; Exercise Test; Exercise Tolerance; Female; Heart Atria; Humans; Male; Matrix Metalloproteinase 2; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Stress, Physiological; Tissue Inhibitor of Metalloproteinase-1

Hypertrophic cardiomyopathy (HCM) shows increased myocardial collagen and disarray. Late gadolinium enhancement in cardiovascular magnetic resonance (CMR) is observed in regions of increased myocardial collagen. The extent of late gadolinium enhancement has been associated with higher prevalence of risk factors of sudden death. The aim of the present study was to describe the clinical characteristics and the presence of risk factors for sudden death in a series of patients from 2 referral centers for HCM in relation to late gadolinium enhancement in CMR.. A total of 120 patients (47 +/- 16 years) were included. All patients fulfilled conventional criteria for HCM. A complete history and clinical examination were performed. Risk factors for sudden death were evaluated. A blinded CMR was performed with late gadolinium enhancement in the left ventricular short-axis orientation. NT pro B-type natriuretic protein (BNP) and C-reactive protein were determined in serum samples. A total of 83 patients (69%) showed late gadolinium enhancement. These patients had higher maximal left ventricular wall thickness (22 +/- 5 versus 17 +/- 3 mm, P < .001), showed more frequently obstruction (42% versus 16%, P = .006), nonsustained ventricular tachycardia (38% versus 8%, P = .001), worse exercise capacity (8 +/- 4 versus 10 +/- 4 METs, P = .003) and increased levels of NT BNP (656 [300-1948] versus 290 [122-948] pg/mL, P = .020). On multivariate analysis, maximal left ventricular wall thickness (P < .001) and nonsustained ventricular tachycardia (P = .011) remained associated with gadolinium-enhanced imaging. Number of risk factors for sudden death was associated with late gadolinium enhancement (OR 2.18, 95%CI 1.45-3.20, P < .001).. Late gadolinium enhancement in CMR is a common finding in HCM. Increased maximal left ventricular wall thickness and nonsustained ventricular tachycardia are associated with late gadolinium enhancement. Associations with risk factors for sudden death and functional status are observed.

Topics: C-Reactive Protein; Cardiomyopathy, Hypertrophic; Contrast Media; Death, Sudden, Cardiac; Exercise Test; Exercise Tolerance; Female; Fibrosis; Gadolinium; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk Factors

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

Delayed gadolinium enhancement (DGE) in cardiac magnetic resonance (CMR) imaging indicates the areas with myocardial fibrosis, which are suggested to be arrhythmogenic substrate in hypertrophic cardiomyopathy (HCM). Elevated brain natriuretic peptide (BNP) is associated with cardiovascular events in HCM. We investigated the grade of DGE in CMR and plasma BNP levels in HCM patients with or without symptomatic ventricular tachycardia (VT) or ventricular fibrillation (VF).. We recruited 26 consecutive untreated HCM patients without any symptoms of heart failure. They were divided into 2 groups: (1) patients with symptomatic VT/VF [VT/VF(+) group, n=6]; (2) patients without symptomatic VT/VF [VT/VF(-) group, n=20]. CMR was performed to evaluate left ventricular geometry and the grade of DGE. Plasma BNP levels, left ventricular mass index, and the number of segments with positive DGE were greater in the VT/VF(+) group than in the VT/VF(-) group (698.1+/-387.6 vs. 226.9+/-256.8 pg/ml, p=0.006; 152.3+/-49.5 vs. 89.5+/-24.1 g/m(2), p=0.003; 9.7+/-5.7 vs. 3.5+/-3.3, p=0.013). On logistic regression, adjusted odds ratio for symptomatic VT/VF was 214 for logBNP (95% confidence interval [CI] 1.2-37,043, p=0.04) and 1.54 for DGE score (95% CI 1.01-2.34, p=0.04).. High plasma BNP levels and the enlarged area of DGE in CMR were associated with symptomatic ventricular tachyarrhythmia. These factors may be useful markers for detecting high-risk patients of sudden cardiac death in HCM.

Topics: Aged; Cardiomyopathy, Hypertrophic; Echocardiography; Echocardiography, Doppler, Color; Female; Gadolinium; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Middle Aged; Natriuretic Peptide, Brain; Tachycardia, Ventricular; Ventricular Fibrillation

The changes of left ventricular diastolic function during exercise are heterogeneous in patients with hypertrophic cardiomyopathy (HCM). We sought to investigate whether exertional changes of mitral annular velocities and plasma N-terminal-pro-B-type natriuretic peptide (BNP) concentration are associated with exercise capacity in patients with HCM. After a comprehensive echocardiographic study, 32 patients with HCM performed symptom-limited graded supine bicycle exercise. Echocardiographic Doppler parameters were measured at each stage of exercise. Blood samples were collected at rest and immediately after exercise to determine the concentration of pro-BNP. Resting pro-BNP (r = -0.620, P < .001), E'(base) (r = 0.414, P = .018), and DeltaE'(50W) (change of E' from base to 50 W of exercise) (r = 0.367, P = .039) were significantly correlated with exercise duration. Left ventricular longitudinal diastolic function reserve index, defined as DeltaE' x E'(base), significantly correlated with exercise duration (at 50 W, r = 0.540, P = .001) independent of age, sex, body mass index, and resting pro-BNP level. When combining DeltaE' x E'(50W) (<5.85 cm(2)/s(2)) and resting pro-BNP (>740 mg/dL), the predictive accuracy for exercise capacity could be improved (for <500 seconds, global chi(2) = 5.84 in pro-BNP vs 8.10 in pro-BNP + DeltaE' x E'(50W), P = .023). The assessment of left ventricular longitudinal diastolic function reserve can provide incremental information to pro-BNP for the prediction of exercise capacity in patients with HCM.

Topics: Cardiomyopathy, Hypertrophic; Echocardiography; Exercise Test; Exercise Tolerance; Female; Fractional Flow Reserve, Myocardial; Humans; Image Interpretation, Computer-Assisted; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Reproducibility of Results; Sensitivity and Specificity; Ventricular Dysfunction, Left

To investigate the relationship between the plasma B-type natriuretic peptide (BNP) level and the occurrence of atrial fibrillation (AF) in nonobstructive hypertrophic cardiomyopathy (HCM) patients.. Patients (n=97) were classified into chronic AF (CAF; n=14), paroxysmal AF (PAF; n=18) and normal sinus rhythm (NSR; n=65) groups. The plasma BNP values were analyzed with logarithmic transformation.. The PAF group showed significantly higher plasma BNP levels than the NSR group [mean (range; -l SD and +1 SD); 248.3 (143.5, 429.5) vs. 78.2 (27.9, 218.8 ng/L), p<0.0001]. The CAF group also showed significantly higher plasma BNP levels than the NSR group [291.1 (161.4, 524.8 ng/L), p<0.0001]. Multivariate analysis with other clinical factors selected association of PAF as one of the factors that increased the plasma BNP level.. The present study indicated that plasma BNP level is clinically useful for identification of nonobstructive HCM patients who have a risk of PAF.

Topics: Aged; Atrial Fibrillation; Biomarkers; Cardiomyopathy, Hypertrophic; Chronic Disease; Echocardiography, Doppler; Female; Fluoroimmunoassay; Follow-Up Studies; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Risk Assessment; Tachycardia, Paroxysmal

In adults with hypertrophic cardiomyopathy (HCM), plasma B-type natriuretic peptide (BNP) levels correlate with dyspnoea class and other markers of disease severity. In children with HCM, symptoms are a poor guide to disease severity and no studies have evaluated the clinical utility of BNP testing.. To assess the relation of BNP levels to symptoms and markers of disease severity in children with HCM.. Forty-four consecutive patients with HCM (27 male, age 10 (area under the receiver operator characteristic curve = 0.875 (p<0.001)).. BNP levels correlate with non-invasive parameters of disease severity in children with HCM, including measures of raised LV filling pressures. For patients in whom evaluation of symptoms is difficult, BNP may be a useful additional tool in the assessment of disease severity.

Topics: Adolescent; Cardiomyopathy, Hypertrophic; Child; Child, Preschool; Diastole; Female; Humans; Infant; Male; Multivariate Analysis; Natriuretic Peptide, Brain; Ventricular Dysfunction, Left

Impaired hyperemic myocardial blood flow (MBF) in hypertrophic cardiomyopathy (HCM), despite normal epicardial coronary arteries, results in microvascular dysfunction. The aim of the present study was to determine the relative contribution of extravascular compressive forces to microvascular dysfunction in HCM. Eighteen patients with symptomatic HCM and normal coronary arteries and 10 age-matched healthy volunteers were studied with PET to quantify resting and hyperemic MBF at a subendocardial and subepicardial level. In HCM patients, MRI was performed to determine left ventricular (LV) mass index (LVMI) and volumes, echocardiography to assess diastolic perfusion time, heart catheterization to measure LV outflow tract gradient (LVOTG) and LV pressures, and serum NH(2)-terminal pro-brain natriuretic peptide (NT-proBNP) as a biochemical marker of LV wall stress. Hyperemic MBF was blunted in HCM vs. controls (2.26 +/- 0.97 vs. 2.93 +/- 0.64 ml min(-1) g(-1), P < 0.05). In contrast to controls (1.38 +/- 0.15 to 1.25 +/- 0.19, P = not significant), the endocardial-to-epicardial MBF ratio decreased significantly in HCM during hyperemia (1.20 +/- 0.11 to 0.88 +/- 0.18, P < 0.01). This pattern was similar for hypertrophied septum and lateral wall. Hyperemic MBF was inversely correlated with LVOTG, NT-proBNP, left atrial volume index, and LVMI (all P < 0.01). Multivariate regression analysis, however, revealed that only LVMI and NT-proBNP were independently related to hyperemic MBF, with greater impact at the subendocardial myocardial layer. Hyperemic MBF is more severely impaired at the subendocardial level in HCM patients. The level of impairment is related to markers of increased hemodynamic LV loading conditions and LV mass. These observations suggest that, in addition to reduced capillary density caused by hypertrophy, extravascular compressive forces contribute to microvascular dysfunction in HCM patients.

Topics: Adult; Aged; Blood Pressure; Cardiomyopathy, Hypertrophic; Coronary Circulation; Endocardium; Female; Heart Rate; Humans; Hyperemia; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Microcirculation; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Perfusion; Pericardium; Positron-Emission Tomography; Ultrasonography; Vascular Resistance

Brain natriuretic peptide (BNP) and N-terminal proBNP (NTproBNP) are well established in the clinic as biomarkers of heart failure. BNP hormone and the inactive NTproBNP are predominantly secreted in the ventricles of the heart in response to pressure overload and, consequently, are being investigated as markers of drug-induced cardiac hypertrophy in rat to support drug development. In the work presented here, an immunoaffinity-based LC/MS/MS assay was developed and validated to measure a selective tryptic fragment of NTproBNP in rat serum. The assay covers the range of 13-329 pg/mL of the tryptic fragment LLELIR, corresponding to 0.1-2.5 ng/mL intact NTproBNP. A stable isotope-labeled version of NTproBNP containing the tryptic fragment LLELI[13C615N1]R was prepared by solid-phase peptide synthesis and was used as an internal standard to minimize assay variability. Due to endogenous NTproBNP present in rat serum, human serum was used as the control matrix, and parallelism between rat and human serum was established by standard addition. Assay accuracy (% RE) and precision (% CV) were measured at three concentrations on each of 4 days and did not exceed 4.2 and 14.5%, respectively. Additionally, study data are presented from the application of this assay in which rats demonstrated a significant increase in NTproBNP serum concentration following administration of an agent known to induce cardiac hypertrophy. In this study, the relationship between serum NTproBNP and cardiac hypertrophy was corroborated by increases in heart weight and magnetic resonance imaging of the test subjects' left ventricle. To our knowledge, this represents the first reported assay for NTproBNP in preclinical species for the assessment of cardiac hypertrophy.

Topics: Amino Acid Sequence; Animals; Biomarkers; Cardiomyopathy, Hypertrophic; Chromatography, Liquid; Disease Models, Animal; Humans; Immunoprecipitation; Mass Spectrometry; Molecular Sequence Data; Natriuretic Peptide, Brain; Rats; Rats, Sprague-Dawley; Time Factors

In human hearts, the transition from cardiac hypertrophy to advanced heart failure (HF) is accompanied by a tremendous increase in Akt phosphorylation. In non-myocardial tissue, the cyclooxygenase (COX)-2 inhibitor celecoxib has been shown to COX-independently inhibit Akt signalling. We studied the effects of celecoxib on Akt signalling and hypertrophic response in myocardium. In rabbit isolated cardiac myocytes celecoxib concentration-dependently (10-100 micromol/L) inhibited the insulin-induced increase in phosphorylation of Akt and its downstream targets, GSK-3beta and p70 S6 kinase, by reducing the phosphorylation level of the upstream regulator PTEN. Inhibition of Akt signalling was accompanied by a significant suppression of characteristic features of cardiac hypertrophy: Celecoxib concentration-dependently suppressed the agonist-induced enhancement of total protein synthesis and BNP mRNA expression. In mice (C57BL/6NCrl) subjected to left ventricular (LV) pressure overload by aortic banding, celecoxib treatment (50mg x kg-1 x d-1) significantly attenuated LV dilation and contractile dysfunction compared with placebo-treated mice. Moreover, celecoxib significantly reduced mortality 8 weeks after banding. Thus, celecoxib can be used to titrate Akt signalling and hypertrophic response in myocardium. It reduces load-induced LV dilation, contractile dysfunction and mortality in vivo. This may have clinical implications for the prevention and treatment of maladaptive hypertrophy and its progression to HF in humans.

Topics: Animals; Blood Pressure; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Celecoxib; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Enzyme Activation; Female; Glycogen Synthase Kinase 3; Heart Failure; Insulin; Mice; Mice, Inbred C57BL; Muscle Proteins; Myocardial Contraction; Myocytes, Cardiac; Natriuretic Peptide, Brain; Phenylephrine; Phosphorylation; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Pyrazoles; Rabbits; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Sulfonamides; Ventricular Dysfunction, Left

Hypertrophic cardiomyopathy (HC) is an inherited heart disease characterized by left ventricular (LV) remodeling. The present study was conducted to investigate the association of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels with LV remodeling on magnetic resonance imaging and procollagen formation in 17 healthy controls and 24 patients with nonobstructive HC attributable to an identical Asp175Asn (aspartic acid to asparagine at codon 175) mutation in the alpha-tropomyosin gene. None of the patients had history of decompensated heart failure, and all patients had normal LV ejection fraction. Patients with HC had higher NT-pro-BNP levels compared with controls (median 60 pmol/L, range <40 to 359, vs <40 pmol/L; p <0.001), but 9 patients with HC had normal NT-pro-BNP levels (<40 pmol/L). In patients with HC, levels of NT-pro-BNP were correlated significantly with LV end-systolic volume index (r = 0.50, p <0.05), LV mass index (r = 0.47, p <0.05), proportion of hypokinetic segments (r = 0.50, p <0.05), and levels of serum aminoterminal propeptide of type III procollagen (r = 0.52, p <0.01). When patients with HC were divided into 3 groups on the basis of their NT-pro-BNP levels, there were statistically significant linear associations of LV end-systolic volume (test for linearity p = 0.034), LV mass index (p = 0.009), proportion of hypokinetic segments (p = 0.016), and levels of serum aminoterminal propeptide of type III procollagen (p = 0.020) with NT-pro-BNP levels over the 3 groups, suggesting a tight relation between LV remodeling and levels of NT-pro-BNP. In conclusion, in patients with nonobstructive HC attributable to an Asp175Asn mutation in the alpha-tropomyosin gene, elevated NT-pro-BNP levels are associated with incipient LV remodeling, suggesting that NT-pro-BNP could be used to diagnose insidious unfavorable LV remodeling in HC.

Topics: Adult; Amino Acid Substitution; Cardiomyopathy, Hypertrophic; Case-Control Studies; Female; Heart Ventricles; Humans; Magnetic Resonance Imaging; Male; Mutation; Natriuretic Peptide, Brain; Peptide Fragments; Procollagen; Systole; Tropomyosin; Ventricular Function, Left; Ventricular Remodeling

Hypertrophic cardiomyopathy (HC) is associated frequently with heart failure symptoms and diastolic dysfunction. Although the influence of brain natriuretic peptide (BNP) levels in the management of patients with systolic dysfunction is evolving, there are few data on the role of BNP in the management of patients with HC. BNP was compared with clinical and echocardiographic variables, including measures of diastolic filling, in 217 patients with HC. BNP values were correlated with New York Heart Association classification, echocardiographic estimates of diastolic filling pressure, and right ventricular systolic pressure even after adjusting for age, gender, renal function, and body habitus. However, the overlap of the BNP levels in these respective categories was notable. BNP values did not correlate with objective measures of exercise capacity, and serial BNP values did not track changes in clinical status. In conclusion, BNP levels in patients with HC are associated with similar subjective and objective measures as have been observed in patients with left ventricular systolic dysfunction, but these correlations are relatively weak and do not allow the precise characterization of clinical status.

Topics: Biomarkers; Cardiomyopathy, Hypertrophic; Diastole; Disease Progression; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Prognosis; Retrospective Studies; Ventricular Dysfunction, Left

N-Terminal-probrain natriuretic peptide (NT-proBNP) plasma levels are elevated in patients with congestive heart failure. Published data concerning the utility of NT-proBNP in hypertrophic cardiomyopathy (HCM) are lacking. Our aim was to evaluate the clinical significance of NT-proBNP in patients with HCM. A blood sample was collected for plasma NT-proBNP measurement from 43 consecutive patients with documented HCM. NT-proBNP was measured using a chemiluminescent immunoassay kit (Roche Diagnostics) on an Elecsys 2010 analyzer. Median value of NT-proBNP was 219 pg/ml (range 8-3 045 pg/ml) in NYHA class I patients, 698 pg/ml (125-2 463 pg/ml) in NYHA class II patients, and 2 683 pg/ml (131-11 542 pg/ml) in NYHA class III and IV patients. NT-proBNP plasma levels were significantly higher across the severity of functional limitation (i.e., NYHA class classification) (P = 0.002). NT-proBNP levels were significantly higher in female than male (P = 0.034), in referral vs nonreferral patients (P = 0.004), in symptomatic vs asymptomatic patients (P = 0.020), in patients with basal subaortic gradient >or=30 mmHg (P = 0.001) and in the patients who were on cardioactive medication (P = 0.010). In univariate analysis NT-proBNP was significantly correlated with age (P < 0.001), left ventricular maximum wall thickness (P = 0.001), left atrial size (P = 0.019), and subaortic gradient >or=30 mmHg (P < 0.001). In multivariate regression analysis, age (P < 0.001), maximum wall thickness (P = 0.007), and gradient >or=30 mmHg (P = 0.027) were independently associated with NT-proBNP levels. Our data support the idea that measurement of plasma NT-proBNP levels in HCM patients is useful to assess their clinical status, especially the severity of hypertrophy and the presence of obstruction, although age must be taken into account.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiomyopathy, Hypertrophic; Cohort Studies; Echocardiography; Female; Heart Failure; Humans; Male; Middle Aged; Models, Statistical; Natriuretic Peptide, Brain; Protein Structure, Tertiary; Regression Analysis

N-terminal pro-brain natriuretic peptide (NT-proBNP) is increased in patients with hypertrophic cardiomyopathy (HCM); however, the determinants of NT-proBNP level have not been clarified in HCM.. This study was performed to determine the relationship between NT-proBNP levels and various echocardiographic variables of patients with HCM and normal left ventricular ejection fraction (LVEF).. We assessed plasma NT-proBNP levels and echocardiographic variables of 36 patients (19 men, 58 +/- 14 years) with HCM and an LVEF of > or = 55%. Echocardiographic variables measured were LV wall thickness, end-diastolic LV internal dimension (LVIDd) and volume (LVEDV), LV mass, and LV mass index (LV mass/body surface area, LVMI). Left ventricular outflow tract pressure gradient, transmitral E and A velocities, deceleration time (DT) of the transmitral E wave, and septal annular E' velocity were measured by Doppler technique. The relationship between echocardiographic variables and plasma NT-proBNP level was analyzed.. The plasma NT-proBNP level was 775.2 +/- 994.2 pg/ml (range 33.1-4729.0 pg/ml). It showed positive correlations with LV end-diastolic septal thickness (r = 0.39, p = 0.010) and LVMI (r = 0.27, p = 0.050), while it revealed negative correlations with LVIDd (r = -0.44, p = 0.004), LVEDV (r = -0.44, p = 0.004) and DT(r = -0.31,p = 0.034). The NT-proBNP level was higher in the patients with than in those without LV diastolic dysfunction (p = 0.033) and was independently related to LVIDd (p = 0.001), LVMI (p = 0.006) and DT (p = 0.031) by multivariate analysis.. In patients with HCM and normal LVEF, the amount of LV hypertrophy and LV diastolic dysfunction may exert a significant role in determining plasma NT-proBNP level.

Topics: Adult; Aged; Aged, 80 and over; Cardiomyopathy, Hypertrophic; Echocardiography; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Stroke Volume; Ventricular Function, Left

Most patients with hypertrophic cardiomyopathy (HC) have reduced maximal oxygen consumption (VO2max) during exercise. The degree of impairment is poorly predicted by the magnitude of hypertrophy, left ventricular (LV) outflow tract obstruction, and other conventional markers of disease severity. The aim of this study was to determine the usefulness of N-terminal-pro-B-type natriuretic peptide (NT-pro-BNP) as a marker of exercise performance in HC. Plasma NT-pro-BNP was measured in 171 consecutive patients (mean age 46 +/- 18 years) who underwent echocardiography and cardiopulmonary exercise testing. The mean log NT-pro-BNP was 2.79 +/- 0.5; log NT-pro-BNP levels were higher in women patients (p = 0.001) and patients with chest pain (p = 0.010), in New York Heart Association class > or = II (p = 0.009), with atrial fibrillation (p < 0.001), with systolic impairment (p = 0.025), and with LV outflow tract obstructions (p < 0.0001). NT-pro-BNP levels were also correlated with maximal wall thickness (r = 0.335, p < 0.0001), left atrial size (r = 0.206, p = 0.007), and the mitral Doppler E/A ratio (r = 0.197, p = 0.012). The mean percent VO2max achieved was 73.8 +/- 22.6%; percent VO2max was smaller in patients with systolic impairment (p = 0.044) and LV outflow tract obstructions (p = 0.025). There were inverse correlations between percent VO2max and NT-pro-BNP (r = -0.352, p = 0.001), LV end-systolic cavity size (r = -0.182, p = 0.031), and left atrial size (r = -0.251, p = 0.003). On multivariate analysis, only NT-pro-BNP was correlated with percent VO2max. A NT-pro-BNP level of 316 ng/L had 78% sensitivity and 44% specificity (area under the curve 0.616) for predicting percent VO2max < 80%. In conclusion, NT-pro-BNP levels correlate with peak oxygen consumption in HC and are more predictive of functional impairment than other conventional markers of disease severity.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathy, Hypertrophic; Echocardiography; Exercise Test; Exercise Tolerance; Female; Humans; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Protein Precursors; Severity of Illness Index

This study was designed to assess the value of plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) levels in predicting clinical courses in 80 patients with hypertrophic cardiomyopathy. Patients were followed for a mean of 571 +/- 294 days for clinical end points, defined as a composite of cardiovascular death and hospitalization for worsening heart failure symptoms. NT-pro-BNP plasma level (hazard ratio 1.6, 95% confidence interval 1.10 to 2.55, p = 0.015) and New York Heart Association (NYHA) functional class (hazard ratio 3.7, 95% confidence interval 1.17 to 12.09, p = 0.025) were the independent variables associated with increased risk for experiencing clinical end points. NT-pro-BNP plasma level > or =1,500 pg/ml detected patients with clinical end points with sensitivity, specificity, and accuracy of 83%, 81%, and 81%, respectively. The hypertrophic cardiomyopathy population was stratified into low-, medium-, and high-risk subgroups using 2 simple variables, NYHA functional class and NT-pro-BNP. Patients in lower NYHA classes and with NT-pro-BNP levels <1,500 pg/ml were significantly free of clinical end points. In conclusion, for patients with hypertrophic cardiomyopathy, plasma levels of NT-pro-BNP seem a reliable parameter to identify those at risk for clinical deterioration at long-term follow-up in conjunction with symptomatic status.

Topics: Biomarkers; Cardiomyopathy, Hypertrophic; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Sensitivity and Specificity

Hypertrophic cardiomyopathy (HCM) is a genetically heterogenous disease caused by mutations in genes that primarily encode sarcomeric proteins. No mutation is identified in up to 40% of HCM patients, suggesting other causative genes exist. Natriuretic peptide precursor B (NPPB; also known as "BNP") is a cardiac hormone involved in body fluid homeostasis and cardiac myocyte growth. NPPB concentrations are markedly increased in patients with ventricular hypertrophy, and it is therefore possible mutations in the NPPB gene could cause HCM.. Genomic DNA was extracted from peripheral blood in 238 consecutive probands with HCM. The coding regions and intron/exon boundaries in the NPPB gene were amplified by PCR, and products were screened for sequence variants using high-performance liquid chromatography, followed by direct DNA sequencing.. Four sequence variants in the NPPB gene were identified in 9 of the 238 probands screened. Two of the variants were intronic, one was a synonymous variant at codon 79, and the final variant resulted in an amino acid substitution from arginine to histidine at codon 47 (Arg47His). The Arg47His variant was identified in a control population consisting of 204 chromosomes at an allelic frequency of 0.5%, and is therefore unlikely to cause disease.. No disease causing mutations were identified in the NPPB gene in this cohort, indicating that mutations in this gene are unlikely to be responsible for HCM.

Topics: Cardiomyopathy, Hypertrophic; DNA Mutational Analysis; Humans; Natriuretic Peptide, Brain; Protein Precursors

Preload-independent pulsed tissue Doppler echocardiography (TDI) and conventional pulsed Doppler echocardiography were used to assess the global left ventricular diastolic function in patients with hypertrophic cardiomyopathy (HCM). Levels of B-type natriuretic peptide (BNP) could be elevated in patients with isolated left ventricular diastolic dysfunction.. The study was to investigate the correlation between BNP levels and the parameters measured by conventional echocardiography and TDI in patients with HCM.. 32 consecutive patients with HCM (21 male, 11 female, mean age 47 +/- 14 years) were studied. Inclusion criteria were: normal sinus rhythm; ejection fraction > or = 50%; absence of moderate to severe mitral regurgitation or prosthetic mitral valve.. In addition to the conventional transmitral flow patterns (E, A, E/A, DT, IVRT) myocardial early (Ea) and late diastolic (Aa) velocities were measured at the lateral and septal border of the mitral annulus by ATL HDI 5000 ultrasound system. Ea/Aa and E/Ea ratios were calculated. NT-proBNP levels were measured by Roche-Elecsys test (immunoassay). Because the distribution of BNP values did not appear to be normal, the values were transformed into a natural logarithm (InBNP).. Mean BNP level was 543 +/- 845 pg/ml. BNP levels negatively correlated with lateral Aa values (r = -0.59, p < 0.001). No significant relationship was observed between BNP levels and other echocardiographic parameters. By stepwise multiple linear regression analysis the only significant predictor of InBNP was lateral Aa value, too (r = -0.467, p < 0.05).. Significant correlation was found between BNP levels and a single TDI parameter characterizing left atrial systolic function, but there was no significant correlation between BNP levels and global left ventricular diastolic function characterized by either conventional echocardiographic or TDI parameters.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Diastole; Echocardiography, Doppler; Female; Humans; Linear Models; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

Although it is not rare to encounter patients with plasma B-type natriuretic peptide (BNP) levels unequivalent to the severity of heart failure (HF), there has been little investigation to clarify the causative background of this phenomenon.. Among the 1,838 outpatients whose plasma BNP was measured, persistently increased levels of BNP above 500 pg/ml was observed for more than 6 months in 14 subjects with few HF symptoms. Among these, all of 4 patients without any following cardiac events (E-/high) for 12 months showed hypertrophic nonobstructive cardiomyopathy (HNCM). When we compared the clinical parameters of these patients with those of 22 HNCM patients without any following cardiac events whose plasma BNP levels were less than 200 pg/ml, there were only 2 clinical characteristics to be distinguished: (i) plasma renin activity (PRA) and norepinephrine (NE) levels were low in spite of markedly increased levels of plasma BNP in E-/high HNCM; and (ii) echocardiographic investigation revealed that only global left atrial fractional shortening was significantly lower in E-/high HNCM.. Plasma BNP levels do not always reflect the severity of HF in HNCM. It might be considered to utilize other clinical parameters such as NE and PRA to recognize HF severity in such patients.

Topics: Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Electrocardiography; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Prognosis; Renin; Severity of Illness Index

We examined the plasma levels of soluble Fas (sFas) or Fas ligand (sFas-L), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in patients with idiopathic nonobstructive (HNCM) and dilated-phase (DHCM) hypertrophic cardiomyopathy. Patients with idiopathic hypertrophic cardiomyopathy (HCM) may deteriorate to DHCM and the pathogenesis is unknown. The levels of these plasma cytokines were measured by ELISA and echocardiography was performed in 38 HNCM and 11 DHCM patients, and 10 normal subjects. The follow-up period was three years. In HNCM, TNF-alpha (43.3 +/- 45.2 versus 16.9 +/- 4.3 pg/mL) and IL-6 (65.1 +/- 86.4 versus 4.0 +/- 2.1 pg/mL) were slightly higher compared to normal subjects and sFas (3.7 +/- 1.2 versus 2.1 +/- 0.7 ng/mL) increased significantly. sFas (3.9 +/- 1.8), TNF-alpha (79.3 +/- 72.4), and IL-6 (234.1 +/- 135.2) in DHCM were significantly increased and only IL-6 was significantly different from HNCM. sFas-L (0.18 +/- 0.08 versus 0.25 +/- 0.05 ng/mL) in HNCM was significantly decreased, and the decrease was marked in DHCM (0.05 +/- 0.02). In HNCM, TNF-alpha was negatively correlated with fractional shortening (r = -0.432, P = 0.0062) or positively with IL-6 (r = 0.665, P < 0.0001), while sFas-L was negatively correlated with IL-6 (r = -0.580, P < 0.0001). DHCM with high sFas had significantly higher cumulative incidences of worsening heart failure. The Fas/Fas-L system and proinflammatory cytokines may play an important role in the status of HCM and its progression to DHCM.

Topics: Aged; Apoptosis; Atrial Natriuretic Factor; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Cytokines; Disease Progression; Echocardiography; Fas Ligand Protein; fas Receptor; Female; Humans; Interleukin-6; Male; Membrane Glycoproteins; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Tumor Necrosis Factor-alpha

Little is known about the relation between left ventricular (LV) functional reserve in response to exercise and cardiac sympathetic nervous function in patients with nonobstructive hypertrophic cardiomyopathy (HCM). We investigated whether an assessment of cardiac sympathetic nervous function by myocardial (123)I-metaiodobenzylguanidine ((123)I-MIBG) scintigraphy might provide a sign of an abnormal LV functional reserve in response to exercise-induced beta-adrenergic stimulation in patients with HCM.. Thirty HCM patients underwent (123)I-MIBG scintigraphy and echocardiography at rest and subsequent biventricular cardiac catheterization at rest and during dynamic exercise. LV pressures were measured using a micromanometer-tipped catheter system. The early and delayed (123)I-MIBG images were quantified as a heart-to-mediastinum ratio (H/M). The plasma levels of brain natriuretic peptide (BNP) and norepinephrine (NE) were also measured.. Patients were divided into 2 groups according to the delayed (123)I-MIBG H/M: group I consisted of 12 patients with a delayed H/M of < or =1.8 and group II had 18 patients with a delayed H/M of >1.8. Both the percentage increase from rest to exercise in LV isovolumic contraction (LV dP/dt(max)) and the percentage shortening of LV pressure half-time (T(1/2)) as an index of isovolumic relaxation were significantly less in group I than in group II (P < 0.05, respectively). A significant linear correlation was observed between the percentage increase in LV dP/dt(max) and (123)I-MIBG H/Ms (early H/M: r = 0.49, P < 0.01; delayed H/M: r = 0.54, P < 0.005, respectively). A significant linear correlation was also observed between the percentage shortening in T(1/2) and (123)I-MIBG H/Ms (early H/M: r = 0.58, P < 0.001; delayed H/M: r = 0.64, P < 0.0005, respectively). The plasma NE levels were significantly higher in group I than in group II (P < 0.01), whereas the plasma BNP levels were comparable in the 2 HCM groups.. beta-Adrenergic enhancement of LV function during exercise may depend on the extent of cardiac sympathetic nervous innervation in HCM patients. Resting myocardial (123)I-MIBG scintigraphy can noninvasively evaluate LV functional reserve in response to exercise in patients with nonobstructive HCM.

Topics: 3-Iodobenzylguanidine; Adult; Aged; Cardiac Catheterization; Cardiomyopathy, Hypertrophic; Echocardiography; Exercise Test; Female; Heart; Humans; Iodine Radioisotopes; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Radionuclide Imaging; Radiopharmaceuticals; Sympathetic Nervous System; Ventricular Function, Left

Hypertrophic cardiomyopathy (HCM) might exhibit not only diastolic, but also latent systolic dysfunction. Therefore combined assessment of both systolic and diastolic function using myocardial performance index (Tei index) can be useful in HCM. Plasma brain natriuretic peptide (BNP) level is reported to be elevated in HCM, but the mechanism of BNP elevation in HCM remains to be established.. The value of Tei index in 45 HCM patients was compared with that of 20 normal control subjects. The HCM patients showed a higher value of Tei index (0.55+/-0.12 vs 0.36+/-0.08, p < 0.0001) and longer isovolumic relaxation and contraction times than control subjects. The plasma BNP level correlated with Tei index in non-obstructive HCM (n = 35, r = 0.61, p < 0.0001), although the correlation was mild when overall HCM patients were included (r = 0.34, p = 0.02). The correlation was still significant after adjusting for age, or the extent and severity of left ventricular hypertrophy. Multiple stepwise regression analysis identified mitral E/A ratio (r = 0.49, F = 13.1) and Tei index (r = 0.37, F = 7.6) as independent predictors of higher plasma BNP level in non-obstructive HCM.. Myocardial performance index was abnormal in HCM, reflecting both systolic and diastolic dysfunction in this disorder. Plasma BNP level correlated with functional assessment by Tei index in non-obstructive HCM.

Topics: Adult; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Diastole; Female; Heart Function Tests; Humans; Male; Middle Aged; Mitral Valve; Myocardial Contraction; Natriuretic Peptide, Brain; Systole

We describe a case of unilateral pulmonary edema occurring in a young woman affected by hypertrophic cardiomyopathy complicated by acute worsening of mitral regurgitation. The relevant role of biochemical markers of heart failure, such as brain natriuretic peptide and carbohydrate antigen 125, in clarifying the final diagnosis of cardiogenic pulmonary edema and modifying treatment accordingly is emphasized.

Topics: Adult; Biomarkers; CA-125 Antigen; Cardiomyopathy, Hypertrophic; Diagnosis, Differential; Echocardiography; Female; Heart Failure; Humans; Mitral Valve Insufficiency; Natriuretic Peptide, Brain; Predictive Value of Tests; Pulmonary Edema; Tomography, X-Ray Computed

Although impaired left ventricular (LV) diastolic function is a prominent feature of hypertrophic cardiomyopathy (HCM), diastolic function and its relation to exercise capacity in apical HCM (ApHCM) has not been explored previously. This study was sought to determine the relationship between diastolic mitral annular velocities combined with conventional Doppler indexes and exercise capacity in patients with ApHCM.. Twenty-nine patients with ApHCM (24 men; mean age +/- SD, 57 +/- 10 years) underwent supine bicycle exercise with simultaneous respiratory gas analysis and two-dimensional and Doppler echocardiographic study.. The mitral inflow velocities (early filling [E], late filling, and deceleration time) were traced and measured. Early diastolic mitral annular velocity (E') was measured at the septal corner of mitral annulus by Doppler tissue imaging (DTI) from the apical four-chamber view. Pro-brain natriuretic peptide (proBNP) was measured at the time of echocardiography using a quantitative electrochemiluminescence immunoassay. E/E' ratio correlated inversely with maximal oxygen uptake (Vo(2)max) [r = - 0.47, p = 0.0106]. There was a significant positive correlation between E' and Vo(2)max (r = 0.41, p = 0.024). However, no correlation was found between conventional two-dimensional, Doppler indices, and proBNP and Vo(2)max). Of all the echocardiographic and clinical parameters assessed, E/E' ratio had the best correlation with exercise capacity (r - 0.47) and was the strongest independent predictor of Vo(2)max by multivariate analysis (p = 0.0106).. DTI-derived indexes (E', E/E' ratio), an estimate of myocardial relaxation and LV filling pressures, correlate with exercise capacity in patients with ApHCM, suggesting that abnormal diastolic function may be a factor limiting exercise capacity.

Topics: Aged; Aged, 80 and over; Cardiomyopathy, Hypertrophic; Exercise Test; Exercise Tolerance; Female; Ferrous Compounds; Humans; Male; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Oxygen Consumption; Peptide Fragments; Ultrasonography, Doppler; Ventricular Dysfunction, Left

In hypertrophic cardiomyopathy (HC), diastolic dysfunction of the left ventricle is a prominent feature caused by myocardial hypertrophy and fibrosis. Angiotensin II has trophic and profibrotic effects on the heart, and the blockade of angiotensin II receptors reverses hypertrophy and fibrosis in human cardiac diseases and in animal HC. This study investigated the short-term (6 months) effects of losartan 100 mg/day in 20 patients with nonobstructive HC, with an emphasis on left ventricular (LV) diastolic dysfunction, compared with 10 patients with HC who were not treated. At the final evaluation, significant changes were observed in the losartan group: a left atrial diameter decrease (p<0.0001), a tissue Doppler early (Ea) mitral annulus diastolic velocity increase (p=0.003) and an E/Ea ratio decrease (p=0.0002), and a significant decrease in plasma levels of the aminoterminal fragment of pro-brain natriuretic peptide (NT-pro-BNP) from a median of 860 to 606 pg/ml (p=0.001). A significant correlation was found between percentage changes in NT-pro-BNP and the E/Ea ratio from baseline to 6 months (r=0.61, p=0.002). In the 2 groups, echocardiographic LV wall and cavity measures did not change. In conclusion, in selected patients with nonobstructive HC, losartan during a 6-month period improved LV diastolic function.

Topics: Adolescent; Adult; Angiotensin II Type 1 Receptor Blockers; Biomarkers; Blood Flow Velocity; Cardiomyopathy, Hypertrophic; Disease Progression; Echocardiography, Doppler; Female; Follow-Up Studies; Heart Ventricles; Humans; Losartan; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Peptide Fragments; Treatment Outcome; Ventricular Function, Left

Plasma B-type natriuretic peptide (BNP) is a sensitive functional marker in heart disease including hypertrophic cardiomyopathy (HCM). The utility of plasma amino-terminal pro-BNP (NT-proBNP) quantification in heart disease has been investigated, but there are no published data regarding this test in HCM.. Plasma NT-proBNP was assessed in 71 patients with HCM and in 40 healthy subjects. Symptomatic status was assessed according to the New York Heart Association classification. M-mode and Doppler echocardiographic data were obtained in all patients and healthy subjects to study their correlations and comparisons (Spearman and Mann-Whitney tests).. Median NT-proBNP was 848 pg/mL in patients and 28 pg/mL in the control group (P < .0001). Patients in New York Heart Association functional class I/II had a median NT-proBNP of 669 pg/mL as compared with 3357 pg/mL for patients in class III/IV (P < .0001). Amino-terminal pro-BNP levels correlated positively with left atrial diameter (r = 0.40, P = .0005), septal thickness (r = 0.35, P = .002), and mitral flow velocity/mitral annulus velocity (E/Ea) ratio (r = 0.42, P < .0001). There was a weak correlation with obstruction (r = 0.23, P = .05), and a significant difference in the medians was observed between obstructive (1651 pg/mL) and nonobstructive (669 pg/mL) HCM groups (P = .01). Patients with Doppler E/Ea ratios > or = 10 had higher NT-proBNP levels than patients with E/Ea < 10 (P < .0001). Multivariate analysis showed that NT-proBNP correlated independently with left atrial diameter (P < .01), hypertrophy (P < .01), and E/Ea (P < .01).. In HCM, plasma NT-proBNP levels are elevated and correlate positively with symptoms of heart failure, hypertrophy severity, and Doppler echocardiographic signs of left ventricular diastolic dysfunction. Further studies are necessary to assess the usefulness of the test in clinical practice and its role as a prognostic marker.

Topics: Adult; Biomarkers; Cardiomyopathy, Hypertrophic; Cross-Sectional Studies; Echocardiography; Female; Heart Atria; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Reference Values

Hypertrophic cardiomyopathy (HCM) has a diverse clinical spectrum that often includes progressive heart failure symptoms and disability. Assessment of symptom severity may be highly subjective, encumbered by the heterogeneous clinical presentation. Plasma B-type natriuretic peptide (BNP) has been used widely as an objective marker for heart failure severity and outcome, predominantly in coronary heart disease with ventricular dilatation and systolic dysfunction.. We prospectively assessed plasma BNP as a quantitative clinical marker of heart failure severity in 107 consecutive HCM patients. BNP showed a statistically significant relationship to magnitude of functional limitation, assessed by New York Heart Association (NYHA) functional class: I, 136+/-159 pg/mL; II, 338+/-439 pg/mL; and III/IV, 481+/-334 pg/mL (P<0.001). Multivariable analysis showed that BNP was independently related to NYHA class as well as age and left ventricular wall thickness (each with a value of P=0.0001). BNP > or =200 pg/mL was the most reliable predictor of heart failure symptoms, with positive and negative predictive values of 63% and 79%, respectively. BNP power in distinguishing patients with or without heart failure symptoms was less than that for differentiating between no (or only mild) and severe symptoms (area under receiver operating characteristic curve=0.75 and 0.83, respectively).. Plasma BNP is independently related to the presence and magnitude of heart failure symptoms in patients with HCM. As a clinical marker for heart failure, BNP is limited by considerable overlap in values between categories of heart failure severity as well as confounding variables of left ventricular wall thickness and age.

Topics: Adult; Age Factors; Aged; Biomarkers; Cardiomyopathy, Hypertrophic; Female; Heart Ventricles; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; ROC Curve; Sensitivity and Specificity; Severity of Illness Index; Ultrasonography

Topics: Abciximab; Angioplasty, Balloon, Coronary; Antibodies, Monoclonal; Antihypertensive Agents; Biomarkers; Blood Pressure Determination; Cardiomyopathy, Hypertrophic; Combined Modality Therapy; Home Nursing; Humans; Hypertension; Immunoglobulin Fab Fragments; Myocardial Infarction; Natriuretic Peptide, Brain; Randomized Controlled Trials as Topic; Recombinant Proteins; Tissue Plasminogen Activator

Patients with hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD) have increased concentrations of various neurohumoral factors. Thus, the aim of the present study was to evaluate the differences in the neurohumoral profiles of HCM and HHD.. Plasma concentrations of epinephrine, norepinephrine, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), angiotensin II and endothelin-1 were measured in 40 patients with HCM, 35 with HHD, and 15 controls. Additionally, the concentrations of these neurohumoral factors in the coronary sinus and aortic root were measured in 12 HCM patients and 10 controls. Plasma concentrations of norepinephrine, ANP and BNP were significantly higher in HCM than HHD and controls. In HCM, there was no significant correlation between the left ventricular mass index and any neurohumoral factor. The plasma BNP concentration significantly correlated with left intraventricular pressure gradient in HCM. There were significant differences in the plasma concentrations of ANP and BNP between HCM with and without left ventricular diastolic dysfunction. Transcardiac production of BNP was significantly higher in patients with obstructive HCM than in those with non-obstructive HCM.. The significant neurohumoral differences between HCM and HHD were the plasma concentrations of norepinephrine, ANP and BNP. In HCM patients, the plasma BNP concentration may reflect the intraventricular pressure gradient and left ventricular diastolic dysfunction whereas the plasma ANP concentration reflects only the left ventricular diastolic dysfunction.

Topics: Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Coronary Vessels; Echocardiography; Female; Heart Ventricles; Humans; Hypertension; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Norepinephrine; Pressure; Ventricular Dysfunction, Left; Ventricular Function

We postulated that both diastolic and systolic load modulate B-type natriuretic peptide (BNP) production in human pressure overload hypertrophy/failure.. In isolated myocytes, diastolic stretch induces BNP messenger ribonucleic acid expression. However, the mechanism of the BNP release in human hypertrophy remains controversial.. In 40 patients with symptomatic aortic stenosis (AS), left ventricular (LV) performance and systolic and diastolic wall stress were calculated from combined invasive and echocardiographic data. Plasma BNP was determined by the rapid point-of-care bedside analyzer (Biosite Triage, Biosite Diagnostics Inc., San Diego, California).. A significant relationship was observed between plasma BNP and pulmonary capillary wedge pressure (p < 0.001), fractional shortening (p = 0.001), and aortic valve area (p = 0.006). Furthermore, a significant correlation was noted between BNP and LV mass index (p = 0.005) as well as between BNP and markers of diastolic load such as LV end-diastolic wall stress (p = 0.011), indexed LV end-diastolic volume (p < 0.001), and isovolumic relaxation time (p = 0.02). Preoperative BNP levels were elevated in patients with AS compared with patients without AS. Plasma BNP was higher in AS patients with impaired versus normal preload reserve (297 +/- 56 pg/ml vs. 168 +/- 44 pg/ml; p = 0.017) and in AS patients with clinical deterioration after valve replacement compared with those without (399 +/- 82 pg/ml vs. 124 +/- 41 pg/ml; p = 0.011).. In patients with AS, BNP appears to be regulated not only by systolic but also by diastolic load. This supports the hypothesis that myocardial stretch modulates BNP production in human pressure overload hypertrophy/failure.

Topics: Adult; Aged; Aged, 80 and over; Aortic Valve Stenosis; Blood Pressure; Cardiomyopathy, Hypertrophic; Case-Control Studies; Diastole; Echocardiography; Female; Follow-Up Studies; Heart; Hemodynamics; Humans; Hypertension; Inpatients; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Pulmonary Wedge Pressure; Stress, Mechanical; Stroke Volume; Systole; Ventricular Function, Left

B-type natriuretic peptide is secreted mainly in the left ventricle in response to elevated wall tension. Plasma levels of the peptide correlate positively with cardiac filling pressures, making it an excellent marker for the presence of left ventricular dysfunction. In hypertrophic cardiomyopathy, enhanced production of B-type natriuretic peptide is observed. However, the relationship of the various structural and functional features present in the disease with the high plasma levels described is not yet fully clarified. In the present study, we prospectively assessed in hypertrophic cardiomyopathy the relationship of plasma NT-proBNP levels with the extent of left ventricular hypertrophy, presence of left ventricular outflow obstruction and echocardiographic parameters of left ventricular diastolic function.. The study population included 190 individuals: 53 patients with hypertrophic cardiomyopathy and well-preserved left ventricular systolic function (group A), 92 healthy relatives with no disease expression (group B), and an additional group of 46 healthy volunteers (group C) as controls for NT-proBNP levels. Groups A and B were characterized clinically and by echocardiography and compared with each other. Plasma NT-proBNP levels were measured (ECLIA-Elecsys proBNP) and compared in the 3 groups of individuals included in the study. In hypertrophic cardiomyopathy patients, correlation was sought between NT-proBNP levels, NYHA functional class and echocardiographic data.. Groups A and B differed (p < 0.001) in septal thickness, maximal wall thickness, left ventricular hypertrophy score, left atrial size, left atrial fractional shortening, derived transmitral filling indices and plasma NT-proBNP levels (group A: 909.9 +/- 1554.2 pg/ml; group B: 40.7 +/- 45.1 pg/ml). Left ventricular diastolic size and pulmonary venous flow velocity-derived indices were similar in the 2 groups. NT-proBNP levels in group B and C (39.4 +/- 34.5 pg/ml) were similar (p = NS). In hypertrophic cardiomyopathy patients, NT-proBNP levels correlate directly with NYHA functional class (r = 0.56, p < 0.001), septal thickness (r = 0.53, p < 0.001), maximal wall thickness (r = 0.59, p < 0.001), left ventricular hypertrophy score (r = 0.63, p < 0.001), left atrial size (r = 0.32, p = 0.023) and mitral deceleration time (r = 0.46, p = 0.001) and inversely with left atrial fractional shortening (r = -0.41, p = 0.005). Functional class also correlates directly with left ventricular hypertrophy score (r = 0.39, p = 0.006), with the most symptomatic patients having the highest scores.. In hypertrophic cardiomyopathy, plasma NT-proBNP levels depend mainly on the severity of left ventricular hypertrophy rather than on the presence of obstruction. Measurement of the peptide may help in the clinical characterization and follow-up of patients with this disease.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Cardiomyopathy, Hypertrophic; Child; Female; Humans; Hypertrophy, Left Ventricular; Male; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Peptide Fragments; Prospective Studies

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are cardiac hormones involved in electrolyte and fluid homeostasis. Our laboratory has investigated the use of ANP and BNP as diagnostic markers of cardiac disease in cats. We hypothesize that the cardiac distribution of ANP and BNP increases in cats with hypertrophic cardiomyopathy (HCM). Accordingly, we evaluated the immunohistochemical distribution of ANP and BNP in hearts of four cats with naturally occurring HCM relative to five healthy controls. Indirect immunoperoxidase was performed with polyclonal immunoglobulin G against feline ANP (1-28) and proBNP (43-56). In control cats, ANP and BNP immunoreactivity was restricted to the atria. Staining for both peptides was most intense adjacent to the endocardial surface. Auricles stained more diffusely than atria for both peptides. The interstitial capillaries and nerve fibers within the heart were positive only for BNP. Atrial immunoreactivity for ANP and BNP was more diffuse and had a less distinctly layered pattern in HCM than in control cats. Ventricular cardiomyocytes of HCM cats were negative for ANP but stained lightly and diffusely for BNP. The capillaries and nerve fibers remained positive for BNP. We conclude that in cats with HCM, the cardiac distribution of ANP and BNP is more diffuse in the atria and that novel expression of BNP in the ventricular cardiomyocytes occurs.

Topics: Animals; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Cat Diseases; Cats; Heart Atria; Heart Ventricles; Immunohistochemistry; Natriuretic Peptide, Brain

The precise function of angiotensin II type 2 receptor (AT2-R) in the mammalian heart in vivo is unknown. Here, we investigated the role of AT2-R in cardiac pressure overload.. Rats were infused with vehicle, angiotensin II (Ang II), PD123319 (an AT2-R antagonist), or the combination of Ang II and PD123319 via subcutaneously implanted osmotic minipumps for 12 or 72 hours. Ang II-induced increases in mean arterial pressure, left ventricular weight/body weight ratio, and elevation of skeletal alpha-actin and beta-myosin heavy chain mRNA levels were not altered by PD123319. In contrast, AT2-R blockade resulted in a marked increase in the gene expression of c-fos, endothelin-1, and insulin-like growth factor-1 in Ang II-induced hypertension. In parallel, Ang II-stimulated mRNA and protein expression of atrial natriuretic peptide were significantly augmented by AT2-R blockade. Moreover, PD123319 markedly increased the synthesis of B-type natriuretic peptide. Furthermore, the expression of vascular endothelial growth factor and fibroblast growth factor-1 was downregulated by Ang II only in the presence of AT2-R blockade.. Our results provide evidence that AT2-R plays a functional role in the cardiac hypertrophic process in vivo by selectively regulating the expression of growth-promoting and growth-inhibiting factors.

Topics: Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Angiotensin II Type 2 Receptor Blockers; Animals; Atrial Natriuretic Factor; Blood Pressure; Cardiomyopathy, Hypertrophic; Fibroblast Growth Factor 1; Gene Expression Regulation; Genes, fos; Heart Rate; Hypertension; Imidazoles; Infusion Pumps, Implantable; Losartan; Male; Natriuretic Peptide, Brain; Proto-Oncogene Proteins c-fos; Pyridines; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 2; RNA, Messenger; Vascular Endothelial Growth Factor A

Atrial fibrillation (AF) occurs in about 20% of patients with hypertrophic cardiomyopathy (HCM). HCM patients with AF have an increased risk for clinical decline and thromboembolism. In addition, AF is known to be associated with the atrial renin-angiotensin system (RAS). However, the relation between AF and the RAS in HCM has not been investigated. We genotyped the insertion/ deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in 138 HCM patients (26 with AF, 112 with sinus rhythm). Distribution of the ACE genotypes (DD, ID, and II) among the total HCM patients was 15%, 46%, and 38%. AF was documented in 3 patients with the DD genotype, 7 with the ID genotype, and 16 with the II genotype (P < 0.03 vs. sinus rhythm group). The odds of AF were 3.2-fold greater in patients with the II genotype than in those with the other genotypes (P = 0.009, 95% confidence interval = 1.3-7.8). Kaplan-Meier curves examining the time to the first documented AF event showed a significant difference between genotypes during the follow-up period (mean 116 months, P < 0.05). These findings suggest that the II genotype of the ACE gene is a significant risk factor for AF in patients with HCM.

Topics: Aged; Atrial Fibrillation; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptidyl-Dipeptidase A; Risk Factors

We measured plasma atrial/brain natriuretic peptide (ANP/BNP) levels at rest and during exercise and correlated the results with various clinical findings, particularly with myocardial ischemia, in asymptomatic hypertrophic cardiomyopathy (HCM).. In patients with HCM, ANP and BNP levels are elevated and exercise-induced myocardial ischemia is common. However, it has not yet been elucidated how these levels at rest and their change with dynamic exercise are related to ischemia.. Levels of ANP and BNP were measured at rest and at peak exercise during (99m)Tc-tetrofosmin scintigraphy in 31 asymptomatic patients with non-obstructive HCM and in 10 control subjects.. Levels of ANP and BNP at rest and the change of ANP and BNP levels (PG/ML) from rest to exercise were significantly greater in HCM than in control subjects (ANP: rest, 53.2 +/- 31.8 vs. 11.6 +/- 6.1; exercise, 114.5 +/- 74.8 vs. 28.3 +/- 23.4. BNP: rest, 156.7 +/- 104.1 vs. 9.8 +/- 9.6; exercise, 201.6 +/- 131.5 vs. 13.2 +/- 14.5). Septal perforator compression (SPC) and exercise-induced ischemia were observed, respectively, in 20 (64.5%) and in 19 (61.3%) patients with HCM. The increment of ANP during exercise was similar between HCM subgroups with or without inducible ischemia. However, BNP levels at rest and BNP increments during exercise were significantly greater in the HCM subgroup with inducible ischemia than in the subgroup without (rest, 190.5 +/- 116.2 vs. 103.1 +/- 48.3; exercise, 250.5 +/- 142.2 vs. 124.2 +/- 58.6). Multiple logistic regression analysis revealed that SPC and BNP levels at rest were independently associated with exercise-induced ischemia.. Measurement of plasma BNP levels at rest may be useful in predicting silent myocardial ischemia in HCM.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Ischemia; Natriuretic Peptide, Brain; Predictive Value of Tests; Reference Values

Topics: Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Hemodynamics; Humans; Natriuretic Peptide, Brain; Ventricular Function, Left

Atrial and brain natriuretic peptide levels closely reflect impaired left ventricular function in patients with heart failure. In the present study we assessed the determinants and the clinical significance of atrial and brain natriuretic peptide plasma levels in hypertrophic cardiomyopathy.. In 44 patients with hypertrophic cardiomyopathy (40+/-15 years) we evaluated: (a) atrial and brain natriuretic peptide plasma levels; (b) left ventricular hypertrophy; (c) left ventricular ejection fraction; (d) transmitral and pulmonary venous flow velocity patterns, and left atrial fractional shortening; (e) left ventricular outflow tract gradient; (f) maximal oxygen consumption. Left ventricular hypertrophy influenced only brain natriuretic peptide levels (r=0.32;P<0.05). Atrial and brain natriuretic peptide plasma levels did not correlate with left ventricular ejection fraction, but correlated with left ventricular outflow tract gradient (r=0.35;P<0.05; and r=0.40, P=0.022, respectively) and left atrial fractional shortening (r=-0.57;P<0.001, and r=-0.35;P<0.05, respectively). Atrial but not brain natriuretic peptide plasma levels were inversely related to maximal oxygen consumption (r=-0.35;P<0.05). By stepwise multiple regression analysis, left atrial fractional shortening and left ventricular outflow tract gradient were the only predictors of atrial and brain natriuretic peptide plasma levels, respectively.. In hypertrophic cardiomyopathy, atrial natriuretic peptide plasma levels are mainly determined by diastolic function: this explains the relationship with exercise tolerance. In contrast, brain natriuretic peptide plasma levels are mainly determined by left ventricular outflow tract gradient.

Topics: Adolescent; Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Echocardiography, Doppler; Exercise Test; Female; Humans; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Regression Analysis; Stroke Volume; Ventricular Function, Left

We examined whether measurement of the plasma BNP concentrations might be useful for the early diagnosis of the existence and severity of disease in patients with heart disease in daily clinical practice.. The plasma BNP and ANP concentrations in 415 patients with heart disease and hypertension and 65 control subjects were measured. Patients with heart disease had higher plasma BNP and ANP concentrations than did those with hypertension or control subjects. Among the etiology of cardiac diseases, specifically dilated cardiomyopathy and hypertrophic cardiomyopathy, was associated with the highest plasma BNP concentrations, whereas dilated cardiomyopathy was associated with the highest plasma ANP concentrations. Plasma BNP concentrations showed an increase as the severity of the heart disease, as graded according to the NYHA classification of cardiac function, increased. In both patients with heart disease and hypertension, the plasma BNP values were higher in those who had abnormalities in their echocardiogram and electrocardiogram as compared to those without any abnormalities. The plasma BNP levels also showed a significant correlation with left ventricular wall thickness and left ventricular mass. On the other hand, the plasma ANP levels showed significant correlations with left ventricular dimension. Receiver operative characteristic analysis revealed that plasma BNP levels showed substantially high sensitivity and specificity to detect the existence of heart diseases.. Measurements of the plasma BNP concentrations is useful to detect the existence of the diseases, and abnormalities of left ventricular function and hypertrophy in patients with heart disease in daily clinical practice.

Topics: Atrial Natriuretic Factor; Biomarkers; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Heart Diseases; Humans; Hypertension; Natriuretic Peptide, Brain; ROC Curve; Sensitivity and Specificity

Topics: Biomarkers; Cardiomyopathy, Hypertrophic; Child; Echocardiography; Electrocardiography; Humans; Natriuretic Peptide, Brain; Phenotype; Prognosis; Sensitivity and Specificity; Ventricular Dysfunction, Left

1. The aim of this study was to elucidate the pathophysiological role of adrenomedullin and the relation between adrenomedullin and other hormones in patients with hypertrophic cardiomyopathy. 2. Fourteen patients with hypertrophic obstructive cardiomyopathy (HOCM), 26 patients with hypertrophic non-obstructive cardiomyopathy (HNCM) and 14 normal control subjects participated in this study. Radioimmunoassay for plasma adrenomedullin concentration was performed with adrenomedullin-M antibody. Plasma levels of endothelin-1, atrial and brain natriuretic peptides and noradrenaline were also measured. 3. Plasma levels of adrenomedullin were higher in patients with hypertrophic cardiomyopathy (8.43 +/- 3.73 pmol/l) than in normal controls (5.24 +/- 0.44 pmol/l, P < 0.005). There was no significant difference between HOCM and HNCM patients. There was a weak correlation between plasma levels of adrenomedullin and total 12-lead QRS voltage in patients with hypertrophic cardiomyopathy (r = 0.323, P < 0.05). 4. Plasma levels of endothelin-1, atrial and brain natriuretic peptides were higher in hypertrophic cardiomyopathy than in normal controls. Endothelin-1 showed no significant difference between HOCM and HNCM patients, but atrial and brain natriuretic peptides were higher in HOCM than in HNCM patients. There was a positive correlation between plasma levels of adrenomedullin and endothelin-1 (r = 0.575, P < 0.0001), but no correlation between plasma levels of adrenomedullin and atrial natriuretic peptide, brain natriuretic peptide and noradrenaline. 5. Our results indicate that adrenomedullin may play an important role to maintain haemodynamics in patients with hypertrophic cardiomyopathy, and its action may be related to endothelin-1 but independent of atrial natriuretic peptide, brain natriuretic peptide and noradrenaline.

Topics: Adrenomedullin; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Endothelin-1; Humans; Middle Aged; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Norepinephrine; Peptides; Vasodilator Agents

Topics: Analysis of Variance; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Humans; Natriuretic Peptide, Brain; Nerve Tissue Proteins

Brain natriuretic peptide (BNP), as a cardiac hormone, is expressed together with atrial natriuretic peptide (ANP) in the ventricles in congestive heart failure. However, the ventricular expression of BNP in hypertrophic cardiomyopathy (HCM) with normal systolic function is still unclear.. The study population consisted of 39 HCM patients with asymmetric septal hypertrophy and 10 control subjects without any specific cardiac disease. Eleven cases of HCM were obstructive (HOCM), and the other 28 cases were nonobstructive (HNCM). All of these patients had a normal ejection fraction. Immunohistochemical analysis of endomyocardial biopsy specimens with specific monoclonal antibodies showed BNP immunoreactivity in the HOCM group (5/10, 50%) but not in the HNCM group (0/22) or in control subjects (0/5). In HOCM, left ventricular end-diastolic pressure was significantly higher in the BNP-positive patients than the BNP-negative patients. Histological changes such as myocardial fiber disarray, hypertrophy of myocytes, and fibrosis were greater in BNP-positive patients than BNP-negative patients in HCM. However, the expression had no significant relation with other clinical parameters. The elevation of the BNP plasma level versus control subjects was marked in both HOCM (85-fold) and HNCM (23-fold). By contrast, the elevation of the ANP plasma level versus control subjects was mild in HOCM (5.7-fold) and HNCM (4.2-fold). The ratio of BNP level to ANP level was higher in HOCM (4.16) than in HNCM (1.46) and control subjects (0.28), and it was higher than the ratio previously reported for severe congestive heart failure (1.72).. These findings suggest that BNP is expressed in the ventricular myocytes of HCM with normal systolic function. In HOCM, ventricular expression of BNP may be augmented in response to both obstruction and diastolic dysfunction.

Topics: Adult; Aged; Atrial Natriuretic Factor; Cardiomyopathy, Hypertrophic; Female; Heart Ventricles; Humans; Immunohistochemistry; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Radioimmunoassay

To elucidate the expression of the brain natriuretic peptide gene in the human heart, we have measured brain natriuretic peptide mRNA levels in hearts using the Northern blot hybridization method. Brain natriuretic peptide mRNA was present with a size of approximately 0.9 kb in the ventricle as well as in the atrium. The brain natriuretic peptide mRNA level in the ventricle was 52% of that in the atrium, whereas the atrial natriuretic peptide mRNA level in the ventricle was approximately two orders of magnitude lower than that in the atrium. Taking atrial and ventricular weights into account, the total amount of brain natriuretic peptide mRNA in the ventricle represented 77% of that in the whole heart. These results demonstrate that most of brain natriuretic peptide mRNA occurs in the ventricle, in contrast with atrial natriuretic peptide mRNA, which is present mainly in the atrium, indicating that the ventricle is a major production site of brain natriuretic peptide.

Topics: Aged; Aged, 80 and over; Blotting, Northern; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Female; Gene Expression Regulation; Heart; Heart Ventricles; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Nerve Tissue Proteins; Reference Values; RNA, Messenger