Sudden cardiac death: investigation of the classical risk factors in a community-based hypertrophic cardiomyopathy cohort.

INTRODUCTION: The identification of high-risk patients in hypertrophic cardiomyopathy (HCM) is still a challenge. The classical clinical risk factors for sudden death have been reported by studies coming from referral HCM cohorts. So far, other studies of community-based HCM populations have not managed to identify risk factors for sudden cardiac death. The aim of the present study was to determine the clinical course of the disease in a community-based HCM population, as well as to identify the clinical factors of sudden death in such a population. METHODS: Three hundred four (304) consecutive HCM patients (202 males, age 48 ± 18.5 years) from 280 different families were assessed. Referral was based on disease diagnosis, irrespective of clinical status or treatment needs. All patients were examined clinically, echocardiographically, by 24h ambulatory electrocardiographic monitoring, and by cardiopulmonary exercise testing at regular intervals, for a period of 56.4 ± 29.9 months. RESULTS: Most patients (n=264/304, 87.2%) were in New York Heart Association functional class I or II. The disease was familial in 60.5%. At initial examination, maximum left ventricular wall thickness was 19 ± 4.4 mm and a left ventricular outflow gradient >30 mmHg was present in 30.9% patients. The annual sudden death mortality was 1.2%. Familial sudden death, non-sustained ventricular tachycardia, severe left ventricular hypertrophy >30 mm, and young age were predictors of sudden cardiac death. CONCLUSIONS: In this community-based HCM population, the risk factors for sudden death were similar to those found in referral cohorts.

Clinical and genetic characterization of families with arrhythmogenic right ventricular dysplasia/cardiomyopathy provides novel insights into patterns of disease expression.

BACKGROUND: According to clinical-pathological correlation studies, the natural history of arrhythmogenic right ventricular dysplasia/cardiomyopathy is purported to progress from localized to global right ventricular dysfunction, followed by left ventricular (LV) involvement and biventricular pump failure. The inevitable focus on sudden death victims and transplant recipients may, however, have created a skewed perspective of a genetic disease. We hypothesized that unbiased representation of the spectrum of disease expression in arrhythmogenic right ventricular dysplasia/cardiomyopathy would require in vivo assessment of families in a genetically heterogeneous population. METHODS AND RESULTS: A cohort of 200 probands and relatives satisfying task force or modified diagnostic criteria for arrhythmogenic right ventricular dysplasia/cardiomyopathy underwent comprehensive clinical evaluation. Desmosomal mutations were identified in 39 individuals from 20 different families. Indices of structural severity correlated with advancing age and were increased in long-term endurance athletes. Fulfillment of modified criteria indicated phenotypically mild disease, whereas asymptomatic status did not. In >80%, ECG, rhythm monitoring, and/or gadolinium-enhanced cardiovascular magnetic resonance were suggestive of LV involvement, the extent of which often was marked among individuals with chain-termination mutations and/or desmoplakin disease. Three patterns of disease expression were identified: (1) classic, with isolated right ventricular disease or LV involvement in association with significant right ventricular impairment; (2) left dominant, with early and prominent LV manifestations and relatively mild right-sided disease; and (3) biventricular, characterized by parallel involvement of both ventricles. CONCLUSIONS: LV involvement in arrhythmogenic right ventricular dysplasia/cardiomyopathy may precede the onset of significant right ventricular dysfunction. Recognition of disease variants with early and/or predominant LV involvement supports adoption of the broader term arrhythmogenic cardiomyopathy.

Natural history and familial characteristics of isolated left ventricular non-compaction.

AIMS: Non-compaction of the left ventricle (LVNC) is a disorder of endomyocardial morphogenesis that results in multiple trabeculations in the left ventricular myocardium. The current literature suggests that LVNC in adults is rare and associated with a poor prognosis. Given that the disorder is present at birth and that several studies have reported asymptomatic familial disease in some patients, we hypothesized that there is a long pre-clinical phase of the disease. The aim of this study was to define the prognosis and familial incidence of LVNC. METHODS AND RESULTS: This study cohort comprised 45 patients (mean age at diagnosis 37 years) consecutively identified at a referral centre for cardiomyopathy over a 10-year period. Twenty-eight patients (62%) had dyspnoea at presentation; 41 (91%) an abnormal ECG; and 30 (66%) left ventricular dilatation and impaired systolic function. Nine patients (20%) had non-sustained ventricular tachycardia on 24 h Holter monitoring. Mean survival from death or transplantation was 97% at 46 months. There were three thromboembolic events in two patients (4%). On systematic family screening, 8 of 32 (25%) asymptomatic relatives had a range of echocardiographic abnormalities, including LVNC, LVNC with impaired systolic function, and left ventricular enlargement without LVNC. CONCLUSION: This study demonstrates that LVNC is associated with a better prognosis than previously reported. In patients with familial disease, relatives may have features consistent with dilated cardiomyopathy rather than LVNC.