Repetitive squatting exercise as a diagnostic predictor in patients with dilated cardiomyopathy.

Objectives: Non-ischaemic dilated cardiomyopathy (DCM) is characterised by a highly variable disease progression. Stress echocardiography and cardiopulmonary exercise testing (CPET) are beneficial in risk assessment, but are labour intensive. Repetitive squatting and standing without weights is a simple exercise (EX). The aim of this study was to investigate the prognostic role of left ventricular (LV) contractile recruitment (CR) after a simple EX of repetitive squatting through three-dimensional (3D) echocardiography. Methods: Patients with DCM (LV ejection fraction (EF)<50%, n=68) and age-matched healthy volunteers (n=25) received a 3D echocardiographic evaluation of LV EF before and after 30 repetitions of squatting-standing EX. CR was defined by the change of LV EF (Δ>4%). Patients were followed up prospectively (2 years) for cardiac death and deteriorating heart failure. Results: During follow-up, 14 cardiac events occurred (21%) with six deaths and eight severe heart failure deteriorations. A poor CR after squatting EX differentiated DCM patients with cardiac events during follow-up as accurately as a reduced peak oxygen consumption (peak VO 2<20 mL/kg/min) (sensitivity: 0.97 and 0.95). Both had a significant incremental diagnostic value over clinical (age, dyspnoea and natriuretic peptide level) or resting echocardiographic parameters (E/E' ratio, LV EF and end-diastolic LV volume) to predict cardiac events (global χ2: 16.0 vs 5.3; 19.5 vs 6.1; P<0.01 for all). Conclusions: The presence of LV CR after EX of repetitive squatting without weights can stratify risk and predict cardiac events in patients with DCM as correct as CPET.

Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies.

The Marfan syndrome (MFS) is a pleiotropic, autosomal dominant disorder of connective tissue with highly variable clinical manifestations including aortic dilatation and dissection, ectopia lentis, and a series of skeletal anomalies. Mutations in the gene for fibrillin-1 (FBN1) cause MFS, and at least 337 mainly unique mutations have been published to date. FBN1 mutations have been found not only in MFS but also in a range of connective tissue disorders collectively termed fibrillinopathies ranging from mild phenotypes, such as isolated ectopia lentis, to severe disorders including neonatal MFS, which generally leads to death within the first two years of life. The present article intends to provide an overview of mutations found in MFS and related disorders and to discuss potential genotype-phenotype correlations in MFS.

TGGE screening of the entire FBN1 coding sequence in 126 individuals with marfan syndrome and related fibrillinopathies.

Mutations in the gene for fibrillin-1 (FBN1) cause Marfan syndrome (MFS), an autosomal dominant heritable disorder of connective tissue with prominent manifestations in the skeletal, ocular, and cardiovascular system. FBN1 mutations have also been identified in a series of related disorders of connective tissue collectively termed type-1 fibrillinopathies. We have developed temperature-gradient gel electrophoresis (TGGE) assays for all 65 FBN1 exons, screened 126 individuals with MFS, other type-1 fibrillinopathies, and other potentially related disorders of connective tissue for FBN1 mutations, and identified a total of 53 mutations, of which 33 are described here for the first time. Several mutations were identified in individuals with fibrillinopathies other than classic Marfan syndrome, including aneurysm of the ascending aorta with only minor skeletal anomalies, and several individuals with only skeletal and ocular involvement. The mutation detection rate in this study was 42% overall, but was only 12% in individuals not fulfilling the diagnostic criteria for MFS, suggesting that clinical overdiagnosis is one reason for the low detection rate observed for FBN1 mutation analysis.