Whole exome sequencing identifies a troponin T mutation hot spot in familial dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) commonly causes heart failure and shows extensive genetic heterogeneity that may be amenable to newly developed next-generation DNA sequencing of the exome. In this study we report the successful use of exome sequencing to identify a pathogenic variant in the TNNT2 gene using segregation analysis in a large DCM family. Exome sequencing was performed on three distant relatives from a large family with a clear DCM phenotype.

Poor prognosis of rare sarcomeric gene variants in patients with dilated cardiomyopathy.

Background: In dilated cardiomyopathy (DCM), the clinical and prognostic implications of rare variants in sarcomeric genes remain poorly understood. To address this question, we analyzed the outcome of rare sarcomeric gene variants in patients enrolled in our Familial Cardiomyopathy Registry.

Methods: DCM families harboring rare sarcomeric variants in MYH6, MYH7, MYBPC3, TNNT2, and TTN were identified.

Danon disease presenting with dilated cardiomyopathy and a complex phenotype.

X-linked dilated cardiomyopathy (XLCM) was first described in 1987 and associated with dystrophin gene (DMD) mutations a decade later in one of the original two families. Here we report long-term follow-up of the second family (XLCM-2), for which a DMD mutation was never found. Analysis of the lysosome-associated membrane protein-2 (LAMP-2) gene detected a novel mutation, confirming a diagnosis of Danon disease.

Prevalence of desmin mutations in dilated cardiomyopathy.

Background: Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known.

Cardiomyopathy, familial dilated.

Dilated cardiomyopathy (DCM) is a heart muscle disease characterized by ventricular dilatation and impaired systolic function. Patients with DCM suffer from heart failure, arrhythmia, and are at risk of premature death. DCM has a prevalence of one case out of 2500 individuals with an incidence of 7/100,000/year (but may be under diagnosed).

Thymopoietin (lamina-associated polypeptide 2) gene mutation associated with dilated cardiomyopathy.

Thymopoietin or TMPO (indicated by its alternative gene symbol, LAP2, in this work) has been proposed as a candidate disease gene for dilated cardiomyopathy (DCM), since a LAP2 product associates with nucleoplasmic lamins A/C, which are encoded by the DCM gene LMNA. We developed a study to screen for genetic mutations in LAP2 in a large collection of DCM patients and families. A total of 113 subjects from 88 families (56 with familial DCM (FDC) and 32 with sporadic DCM) were screened for LAP2 mutations using denaturing high-performance liquid chromatography and sequence analysis.

Alpha-myosin heavy chain: a sarcomeric gene associated with dilated and hypertrophic phenotypes of cardiomyopathy.

Background: Mutations in the beta-myosin heavy-chain (betaMyHC) gene cause hypertrophic (HCM) and dilated (DCM) forms of cardiomyopathy. In failing human hearts, downregulation of alphaMyHC mRNA or protein has been correlated with systolic dysfunction. We hypothesized that mutations in alphaMyHC could also lead to pleiotropic cardiac phenotypes, including HCM and DCM.

Fatal myocarditis: morphologic and clinical features.

Background: Autopsy studies report a frequency of myocarditis ranging from 0.11 to 5.5% in the general population, reaching almost 50% in selected groups.

Idiopathic dilated cardiomyopathy: prognostic significance of electrocardiographic and electrophysiologic findings in the nineties.

Background: With the exception of a few cases such as aborted sudden cardiac death, sustained ventricular tachycardia, and syncope of unexplained origin, there is no consensus on the clinical findings identifying patients with idiopathic dilated cardiomyopathy with an increased risk of sudden cardiac death or malignant ventricular arrhythmias.

Methods: To verify whether electrocardiographic and arrhythmologic features could be useful for prognostic stratification, 78 consecutive patients with an invasive diagnosis of idiopathic dilated cardiomyopathy, but without symptomatic ventricular arrhythmias, were enrolled in a prospective study. Signal-averaged ECG, 24 to 48 hour ECG monitoring and electrophysiologic study were performed at the time of diagnosis to identify arrhythmogenic predictors of outcome.

[The natural history of dilated cardiomyopathy: a review of the Heart Muscle Disease Registry of Trieste].

Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers.

[How the natural history of dilated cardiomyopathy has changed. Review of the Registry of Myocardial Diseases of Trieste].

Dilated cardiomyopathy (DCM), a heart muscle disease characterized by ventricular dilation and dysfunction, is a leading cause of mortality and morbidity. In the present paper we will consider the main results of studies on the natural history of DCM in 581 consecutive patients prospectively enrolled and systematically followed in the Heart Muscle Disease Registry of Trieste in the last 25 years. In the last decades prognosis of DCM significantly improved over time, mainly as a consequence of optimized treatment with ACE-inhibitors and beta-blockers.

Familial hypertrophic cardiomyopathy: clinical features, molecular genetics and molecular genetic testing.

Hypertrophic cardiomyopathy is a Mendelian disease characterized by cardiac hypertrophy. It has a prevalence of 1:500 individuals and is the most common cause of sudden death in the young. Other complications include heart failure and the need for heart transplantation.

Usefulness of exercise test in selected patients coming to the emergency department for acute chest pain.

Background: The management of patients with acute chest pain is a common and difficult challenge for clinicians. In our emergency department (ED) a systematic protocol that involves the use of the exercise test for the management of patients with chest pain of suspected cardiac origin is presently running. The aim of the present study was to evaluate the feasibility of such a test in this setting, in terms of the safety and satisfactory follow-up of these patients discharged home.

Natural history of dilated cardiomyopathy due to lamin A/C gene mutations.

Objectives: We examined the prevalence, genotype-phenotype correlation, and natural history of lamin A/C gene (LMNA) mutations in subjects with dilated cardiomyopathy (DCM).

Background: Mutations in LMNA have been found in patients with DCM with familial conduction defects and muscular dystrophy, but the clinical spectrum, prognosis, and clinical relevance of laminopathies in DCM are unknown.

Background: A cohort of 49 nuclear families, 40 with familial DCM and 9 with sporadic DCM (269 subjects, 105 affected), was screened for mutations in LMNA using denaturing high-performance liquid chromatography and sequence analysis.