Relationship between aetiology and left ventricular systolic dysfunction in hypertrophic cardiomyopathy.

BACKGROUND: Severe left ventricular (LV) systolic dysfunction is an uncommon complication of hypertrophic cardiomyopathy (HCM) that is associated with poor prognosis. Small observational series suggest that patients with rare causes of HCM are more likely to develop systolic impairment than those with idiopathic disease or mutations in cardiac sarcomeric protein genes. The aim of this study was to test this hypothesis by comparing the prevalence of systolic dysfunction and its impact on prognosis in patients with different causes of HCM. METHODS AND RESULTS: 1697 patients (52 (40-63) years, 1160 (68%) males) with HCM followed at two European referral centres were studied. Diagnosis of specific aetiologies was made on the basis of clinical examination, cardiac imaging and targeted genetic and biochemical testing. The primary survival outcome was all-cause mortality or heart transplantation (HTx) for end-stage heart failure (HF). Secondary outcomes were HF-related death, sudden cardiac death, stroke-related death and non-cardiovascular death. Systolic dysfunction (LV ejection fraction <50% by two-dimensional (2D) echocardiography) at first evaluation was more frequent in rare phenocopies than in idiopathic or sarcomeric HCM (105/409 (26%) vs 40/1288 (3%), respectively (p<0.0001)). All-cause death/HTx and HF-related death were more frequent in rare phenocopies compared with idiopathic or sarcomeric HCM (p<0.0001). All-cause mortality and HF-related death were highest in patients with cardiac amyloidosis (p<0.0001). CONCLUSIONS: In adults with HCM, LV systolic dysfunction is more frequent in those with rare phenocopies. When combined with age at presentation, it is a marker for specific aetiologies and is associated with poorer long-term survival.

Gender-related risk of myocardial involvement in systemic amyloidosis.

To investigate associations between gender and myocardial involvement in systemic amyloidosis, we reviewed all patients presenting between 1994 and September 2006 in our institutional network (100 AL and 98 familial transthyretin-related amyloidosis (ATTR) patients, plus 12 elderly men with senile systemic amyloidosis). We focused on echocardiographic descriptors of myocardial involvement (height-indexed mean left ventricular (LV) wall thickness, LV mass index), and baseline LV function. Among familial ATTR patients, female prevalence was lower within the highest tertile of either echocardiographic indicator of myocardial involvement. Gender was independently associated with height-indexed mean LV wall thickness (as were gene mutations). Female prevalence appeared rather similar across the different neurological stages. Within the subgroup of familial ATTR patients with amyloidotic cardiomyopathy, women tended to display a considerably less severe morphological and functional echocardiographic profile. We explored the possible role of female sex hormones by considering menopausal status: women in the highest tertile of mean LV wall thickness index were more often postmenopausal than those in the other two tertiles and had a much higher ( approximately 15 years) mean age; analogous age-related associations were not observable for men. In conclusion, these findings raise the hypothesis that some biological characteristic associated with female gender protects against myocardial involvement in familial ATTR.