Abstract Background: Right ventricular (RV) dysfunction is a well-known predictor of mortality in patients with valvular heart disease (VHD). The assessment of RV function is often difficult due to complex geometry and hemodynamic factors. We aim to analyze RV function in patients with severe mitral and/or aortic valve disease using two-dimensional strain (2DS) imaging and conventional echocardiographic parameters, comparing it with right ventricular ejection fraction (RVEF) measured by three-dimensional echocardiography (3DE). Methods: Fifty-three patients with severe mitral and/or aortic VHD underwent complete transthoracic echocardiogram in the preoperative setting for cardiac surgery, including conventional echocardiographic parameters of RV function and speckle-tracking derived 2DS indices: RV global longitudinal strain (RVGS) and RV free wall longitudinal strain (RVFWS). Conventional echocardiographic and 2DS parameters were compared with real-time 3DE RVEF using Spearman correlation test. For comparison between two groups of patients based on the presence of RV dysfunction (normal RVEF ≥ 44% - A, abnormal RVEF < 44% - B), we used nonparametric Mann-Whitney U test. ROC (receiver operating characteristic) curve analysis was used to assess the clinical utility of all RV function variables in defining RV dysfunction. P values <0,05 were considered statistically significant. Results: We found a significant correlation between all parameters and RVEF (p<0.05), with best results for RV fractional area change (FAC), RVGS, and RVFWS. Dividing the population into two-groups based on RVEF, we found 14 patients with RV dysfunction (27.4%), and significant differences between the groups for all RV function variables. For detection of RV dysfunction defined by 3DE, ROC curve analysis showed the best area under the curve (AUC) for RVGS (0.872), RVFWS (0.851) and FAC (0.932). Conclusions: We observed significant correlation between RVGS, RVFWS and RVEF, with good accuracy in detecting RV dysfunction, comparable to FAC and better than other conventional parameters of RV function assessment. The evaluation of RV myocardial deformation with 2DS may have additional diagnostic and prognostic value in patients with severe left-sided VHD. (Int J Cardiovasc Sci. 2018; [online].ahead print, PP.0-0).

Resumo A cardiomiopatia hipertrófica (CMH) é uma doença autossômica dominante causada por mutações em genes que codificam as proteínas dos sarcômeros. É a principal causa de morte súbita cardíaca em atletas jovens de alto nível. Estudos têm demonstrado um pior prognóstico associado a mutações específicas. A associação entre genótipo e fenótipo em CMH tem sido objeto de diversos estudos desde a descoberta da origem genética dessa doença. Este trabalho apresenta o efeito de uma mutação composta em MYBPC3 na expressão fenotípica da CMH. Uma família na qual um jovem tem o diagnóstico clínico de CMH foi submetida à investigação clínica e genética. As regiões codificadoras dos genes MYH7, MYBPC3 e TNNT2 foram sequenciadas e analisadas. O probando apresenta uma manifestação maligna da doença e é o único em sua família a desenvolver CMH. A análise genética pelo sequenciamento direto dos três principais genes relacionados à essa doença identificou uma variante em heterozigose composta (p.E542Q e p.D610H) em MYBPC3. A análise da família mostrou que os alelos p.E542Q e p.D610H tem origem paterna e materna, respectivamente. Nenhum familiar portador de um dos alelos variantes manifestou sinais clínicos de CMH. Sugerimos que a expressão heterozigótica bialélica de p.E542Q e p.D610H pode ser responsável pelo fenótipo severo da doença encontrada no probando.

Abstract Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disease caused by mutations in genes encoding sarcomere proteins. It is the major cause of sudden cardiac death in young high-level athletes. Studies have demonstrated a poorer prognosis when associated with specific mutations. The association between HCM genotype and phenotype has been the subject of several studies since the discovery of the genetic nature of the disease. This study shows the effect of a MYBPC3 compound variant on the phenotypic HCM expression. A family in which a young man had a clinical diagnosis of HCM underwent clinical and genetic investigations. The coding regions of the MYH7, MYBPC3 and TNNT2 genes were sequenced and analyzed. The proband present a malignant manifestation of the disease, and is the only one to express HCM in his family. The genetic analysis through direct sequencing of the three main genes related to this disease identified a compound heterozygous variant (p.E542Q and p.D610H) in MYBPC3. A family analysis indicated that the p.E542Q and p.D610H alleles have paternal and maternal origin, respectively. No family member carrier of one of the variant alleles manifested clinical signs of HCM. We suggest that the MYBPC3-biallelic heterozygous expression of p.E542Q and p.D610H may cause the severe disease phenotype seen in the proband.