Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene.

BACKGROUND: Mutations in MYBPC3 encoding myosin binding protein C belong to the most frequent causes of hypertrophic cardiomyopathy (HCM) and may also lead to dilated cardiomyopathy (DCM). MYBPC3 mutations initially were considered to cause a benign form of HCM. The aim of this study was to examine the clinical outcome of patients and their relatives with 18 different MYBPC3 mutations. METHODS: 87 patients with HCM and 71 patients with DCM were screened for MYBPC3 mutations by denaturing gradient gel electrophoresis and sequencing. Close relatives of mutation carriers were genotyped for the respective mutation. Relatives with mutation were then evaluated by echocardiography and magnetic resonance imaging. A detailed family history regarding adverse clinical events was recorded. RESULTS: In 16 HCM (18.4%) and two DCM (2.8%) index patients a mutation was detected. Seven mutations were novel. Mutation carriers exhibited no additional mutations in genes MYH7, TNNT2, TNNI3, ACTC and TPM1. Including relatives of twelve families, a total number of 42 mutation carriers was identified of which eleven (26.2%) had at least one adverse event. Considering the twelve families and six single patients with mutations, 45 individuals with cardiomyopathy and nine with borderline phenotype were identified. Among the 45 patients, 23 (51.1%) suffered from an adverse event. In eleven patients of seven families an unexplained sudden death was reported at the age between 13 and 67 years. Stroke or a transient ischemic attack occurred in six patients of five families. At least one adverse event occurred in eleven of twelve families. CONCLUSION: MYBPC3 mutations can be associated with cardiac events such as progressive heart failure, stroke and sudden death even at younger age. Therefore, patients with MYBPC3 mutations require thorough clinical risk assessment.

Use of cardiovascular magnetic resonance for risk stratification in chronic heart failure: prognostic value of late gadolinium enhancement in patients with non-ischaemic dilated cardiomyopathy.

OBJECTIVE: Owing to its variable clinical course, risk stratification is of paramount importance in non-ischaemic dilated cardiomyopathy (DCM). The goal of this study was to investigate the long-term prognostic significance of late gadolinium enhancement (LGE) as detected by contrast-enhanced cardiovascular magnetic resonance (CE-CMR) in patients with DCM. DESIGN: Observational cohort study. Setting University hospital. PATIENTS: 184 consecutive patients with DCM. MEASUREMENTS: CE-CMR was performed on a 1.5 T clinical scanner. Presence, extent and patterns of LGE were determined by two independent observers. OUTCOME MEASURES: Patients were followed for the composite end point of cardiac death, hospitalisation for decompensated heart failure, or appropriate implantable cardioverter defibrillator discharge for a mean±SEM of 685±30 days. RESULTS: LGE was detected in 72/184 patients (39%) and was associated with a lower left ventricular (LV) ejection fraction (31% (20.9-42.2%) vs 44% (33.1-50.9%), p<0.001), higher LV end-diastolic volume index (133 (116-161) ml/m(2) vs 109 (92.7-137.6) ml/m(2), p<0.001) and higher LV mass (80 (67.1-94.8) g/m(2) vs 65.8 (55.2-82.9) g/m(2), p<0.001). Patients in whom LGE was present were more likely to experience the composite end point (15/72 vs 6/112, p=0.002). Receiver operating characteristic curve analysis revealed a LGE of >4.4% of LV mass as optimal discriminator for the composite end point. When entered into multivariate Cox regression analysis, LGE retained its independent predictive value, yielding an associated HR of 3.4 (95% CI 1.26 to 9). CONCLUSION: The presence of LGE in this large DCM patient cohort is associated with pronounced LV remodelling, functional impairment and an adverse outcome. Further research is necessary to determine whether these findings will aid the clinical management of DCM patients.

Adjuvant Use of Ivabradine in Acute Heart Failure due to Myocarditis.

We report two cases of young men in whom acute heart failure due to myocarditis was diagnosed. The patients had been transferred to the intensive care unit (ICU) with commencing symptoms of acute heart failure and consecutive multiorgan failure for further treatment and to evaluate the indication for implantation of a ventricular assist device or for high urgent orthotopic heart transplantation. In both patients, the I(f)-channel inhibitor ivabradine was administered off-label to provide selective heart rate reduction, and thus support hemodynamic stabilization. Though currently considered off-label use in patients suffering from severe hypotension and acute heart failure, the use of ivabradine may beneficially influence outcome by allowing optimization of the patient's heart rate concomitant to initial measures of clinical stabilization.