RESUMO
AIMS: To investigate whether phospholamban gene (PLN) mutations underlie patients diagnosed with either arrhythmogenic right ventricular cardiomyopathy (ARVC) or idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: We screened a cohort of 97 ARVC and 257 DCM unrelated index patients for PLN mutations and evaluated their clinical characteristics. PLN mutation R14del was identified in 12 (12 %) ARVC patients and in 39 (15 %) DCM patients. Haplotype analysis revealed a common founder, estimated to be between 575 and 825 years old. A low voltage electrocardiogram was present in 46 % of R14del carriers. Compared with R14del- DCM patients, R14del+ DCM patients more often demonstrated appropriate implantable cardioverter defibrillator discharge (47 % vs. 10 % , P < 0.001), cardiac transplantation (18 % vs. 2 % , P < 0.001), and a family history for sudden cardiac death (SCD) at < 50 years (36 % vs. 16 % , P = 0.007). We observed a similar pattern in the ARVC patients although this was not statistically significant. The average age of 26 family members who died of SCD was 37.7 years. Immunohistochemistry in available myocardial samples revealed absent/depressed plakoglobin levels at intercalated disks in five of seven (71 %) R14del+ ARVC samples, but in only one of nine (11 %) R14del+ DCM samples (P = 0.03). CONCLUSIONS: The PLN R14del founder mutation is present in a substantial number of patients clinically diagnosed with DCM or ARVC. R14del+ patients diagnosed with DCM showed an arrhythmogenic phenotype, and SCD at young age can be the presenting symptom. These findings support the concept of 'arrhythmogenic cardiomyopathy'.
Assuntos
Displasia Arritmogênica Ventricular Direita/genética , Proteínas de Ligação ao Cálcio/genética , Cardiomiopatia Dilatada/genética , Adulto , Morte Súbita Cardíaca , Feminino , Humanos , Masculino , Mutação , Fenótipo , Estudos Retrospectivos , Estatística como AssuntoRESUMO
Sudden cardiac death occurs in a minority of patients in the absence of structural or functional abnormalities. In this category, pure electrical heart diseases are responsible for a large number of these unexpected deaths. These conditions include the long QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, short QT syndrome (collectively referred to as channelopathies) and idiopathic ventricular fibrillation. This article reviews the current molecular understanding of the electrical diseases of the heart associated with sudden cardiac death, and provides a summary of the causal genes and a flowchart with an overview of the genotype-phenotype correlation of the most common arrhythmia syndromes.
Assuntos
Arritmias Cardíacas/genética , Canais Iônicos/genética , Sinalização do Cálcio/genética , Catecolaminas/genética , Eletrocardiografia , Epilepsia/complicações , Epilepsia/genética , Gastroenteropatias/genética , Sistema de Condução Cardíaco , Humanos , MutaçãoRESUMO
The aetiology of peripartum cardiomyopathy (PPCM) is still largely unknown. Recent evidence suggests that the breakdown products from prolactin can induce cardiomyopathy. Prolactin secretion can be reduced with bromocriptine which had beneficial effects in a small study. We present a case of a patient with PPCM who received cabergoline, a strong and long lasting antagonist of prolactin secretion. Following treatment, her prolactin levels dropped swiftly. N-terminal pro-BNP levels, which had remained high up to that point, dropped within 1 day (7006 to 4408 pg/mL). Echocardiographic left ventricular ejection fraction recovered from 26% on day 4 postpartum to 32% and later 47% on days 2 and 5 after cabergoline treatment. To our knowledge, this is the first description of a case of PPCM in which cabergoline was administered.