Impact of DCM-Causing Genetic Background on Long-Term Response to Cardiac Resynchronization Therapy.

Background: Patients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block benefit from cardiac resynchronization therapy (CRT). However, a large heterogeneity of response to CRT is described. Several predictors of response to CRT have been identified, but the role of the underlying genetic background is still poorly explored.

Phenotypic Expression, Natural History, and Risk Stratification of Cardiomyopathy Caused by Filamin C Truncating Variants.

Background: Filamin C truncating variants () cause a form of arrhythmogenic cardiomyopathy: the mode of presentation, natural history, and risk stratification of remain incompletely explored. We aimed to develop a risk profile for refractory heart failure and life-threatening arrhythmias in a multicenter cohort of carriers.

Methods: carriers were identified from 10 tertiary care centers for genetic cardiomyopathies.

truncations cause arrhythmogenic right ventricular cardiomyopathy.

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease that affects predominantly the right ventricle and is part of the spectrum of arrythmogenic cardiomyopathies (ACMs). ARVC is a genetic condition; however, a pathogenic gene variant is found in only half of patients.

Objective: Filamin C gene truncations () have recently been identified in dilated cardiomyopathy with ventricular arrhythmia and sudden cardiac death, a phenotype partially overlapping with ARVC and part of the ACM spectrum.

Genetic Risk of Arrhythmic Phenotypes in Patients With Dilated Cardiomyopathy.

Background: Genotype-phenotype correlations in dilated cardiomyopathy (DCM) and, in particular, the effects of gene variants on clinical outcomes remain poorly understood.

Objectives: The purpose of this study was to investigate the prognostic role of genetic variant carrier status in a large cohort of DCM patients.

Methods: A total of 487 DCM patients were analyzed by next-generation sequencing and categorized the disease genes into functional gene groups.

The S-wave angle identifies arrhythmogenic right ventricular cardiomyopathy in patients with electrocardiographically concealed disease phenotype.

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries risk of sudden death. We hypothesize that the S-wave angle differentiates ARVD/C with otherwise normal electrocardiograms from controls.

Materials And Methods: All patients met Task Force 2010 definite ARVD/C criteria.

Filamin C Truncation Mutations Are Associated With Arrhythmogenic Dilated Cardiomyopathy and Changes in the Cell-Cell Adhesion Structures.

Objectives: The purpose of this study was to assess the phenotype of Filamin C (FLNC) truncating variants in dilated cardiomyopathy (DCM) and understand the mechanism leading to an arrhythmogenic phenotype.

Background: Mutations in FLNC are known to lead to skeletal myopathies, which may have an associated cardiac component. Recently, the clinical spectrum of FLNC mutations has been recognized to include a cardiac-restricted presentation in the absence of skeletal muscle involvement.

Right precordial-directed electrocardiographical markers identify arrhythmogenic right ventricular cardiomyopathy in the absence of conventional depolarization or repolarization abnormalities.

Background: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) carries a risk of sudden death. We aimed to assess whether vectorcardiographic (VCG) parameters directed toward the right heart and a measured angle of the S-wave would help differentiate ARVD/C with otherwise normal electrocardiograms from controls.

Methods: Task Force 2010 definite ARVD/C criteria were met for all patients.

Lifelong arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy: distribution of events and impact of periodical reassessment.

Aims: The arrhythmic risk stratification of arrhythmogenic right ventricular cardiomyopathy (ARVC) remains controversial. We evaluated the long-term distribution of life-threatening arrhythmic events assessing the impact of periodical risk reassessment.

Methods And Results: Ninety-eight ARVC patients with no previous major ventricular arrhythmias were retrospectively analysed.

Association between mutation status and left ventricular reverse remodelling in dilated cardiomyopathy.

Objective: To explore the genetic landscape of a well selected dilated cardiomyopathy (DCM) cohort, assessing the possible relation between different genotypes and left ventricular reverse remodelling (LVRR).

Methods: A cohort of 152 patients with DCM from the Heart Muscle Disease Registry of Trieste has been studied by next-generation sequencing (NGS). Patients were grouped into different 'gene-clusters' with functionally homogeneous genetic backgrounds.

Multilevel analyses of SCN5A mutations in arrhythmogenic right ventricular dysplasia/cardiomyopathy suggest non-canonical mechanisms for disease pathogenesis.

Aims: Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) is often associated with desmosomal mutations. Recent studies suggest an interaction between the desmosome and sodium channel protein Na1.5.

Gene Splice Mutations Cause Dilated Cardiomyopathy.

Objective: To identify novel dilated cardiomyopathy (DCM) causing genes, and to elucidate the pathological mechanism leading to DCM by utilizing zebrafish as a model organism.

Background: DCM, a major cause of heart failure, is frequently familial and caused by a genetic defect. However, only 50% of DCM cases can be attributed to a known DCM gene variant, motivating the ongoing search for novel disease genes.

Insights into mildly dilated cardiomyopathy: temporal evolution and long-term prognosis.

Aims: Mildly dilated cardiomyopathy (MDCM) has been proposed as a subtype of dilated cardiomyopathy (DCM) characterized by systolic dysfunction in the absence of significant LV dilatation. Few data on the characteristics and outcomes of MDCM patients are available. We sought to assess the main features and the long-term natural history of MDCM.

Risk Stratification in Arrhythmic Right Ventricular Cardiomyopathy Without Implantable Cardioverter-Defibrillators.

Objectives: The primary objective of this study is risk stratification of patients with arrhythmic right ventricular cardiomyopathy (ARVC).

Background: There is a need to identify those who need an automatic implantable defibrillator (ICD) to prevent sudden death.

Methods: This is an analysis of 88 patients with ARVC from three centers who were not treated with an ICD.

[Dilated cardiomyopathy: a dynamic disease - clinical course, reverse remodeling and prognostic stratification].

Dilated cardiomyopathy (DCM) is a relatively rare primary heart muscle disease with genetic or post-inflammatory etiology. In the last decade, the incidence and prevalence of the disease have significantly increased as a consequence of an earlier diagnosis supported by extensive familial screening programs and by the improvement in diagnostic techniques. Moreover, current therapeutic strategies have deeply modified the prognosis of DCM with a dramatic reduction in mortality.

Role of Titin Missense Variants in Dilated Cardiomyopathy.

Background: The titin gene (TTN) encodes the largest human protein, which plays a central role in sarcomere organization and passive myocyte stiffness. TTN truncating mutations cause dilated cardiomyopathy (DCM); however, the role of TTN missense variants in DCM has been difficult to elucidate because of the presence of background TTN variation.

Methods And Results: A cohort of 147 DCM index subjects underwent DNA sequencing for 313 TTN exons covering the N2B and N2BA cardiac isoforms of TTN.

Arrhythmogenic Phenotype in Dilated Cardiomyopathy: Natural History and Predictors of Life-Threatening Arrhythmias.

Background: Patients with dilated cardiomyopathy (DCM) may present with ventricular arrhythmias early in the disease course, unrelated to the severity of left ventricular dysfunction. These patients may be classified as having an arrhythmogenic DCM (AR-DCM). We investigated the phenotype and natural history of patients with AR-DCM.

GENETIC CAUSES OF DILATED CARDIOMYOPATHY.

Dilated cardiomyopathy is a disease of the myocardium characterized by left ventricular dilatation and/or dysfunction, affecting both adult and pediatric populations. Almost half of cases are genetically determined with an autosomal pattern of inheritance. Up to 40 genes have been identified affecting proteins of a wide variety of cellular structures such as the sarcomere, the nuclear envelope, the cytoskeleton, the sarcolemma and the intercellular junction.

Arrhythmogenic right ventricular cardiomyopathy: From genetics to diagnostic and therapeutic challenges.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease characterized by myocyte loss and fibro-fatty tissue replacement. Diagnosis of ARVC remains a clinical challenge mainly at its early stages and in patients with minimal echocardiographic right ventricular (RV) abnormalities. ARVC shares some common features with other cardiac diseases, such as RV outflow ventricular tachycardia, Brugada syndrome, and myocarditis, due to arrhythmic expressivity and biventricular involvement.