Hot Phases Cardiomyopathy: Pathophysiology, Diagnostic Challenges, and Emerging Therapies.

Purpose Of Review: Hot phases are a challenging clinical presentation in arrhythmogenic cardiomyopathy (ACM), marked by acute chest pain and elevated cardiac troponins in the absence of obstructive coronary disease. These episodes manifest as myocarditis and primarily affect young patients, contributing to a heightened risk of life-threatening arrhythmias and potential disease progression. This review aims to synthesize recent research on the pathophysiology, diagnostic challenges, and therapeutic management of hot phases in ACM.

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.

Role of arrhythmic phenotype in prognostic stratification and management of dilated cardiomyopathy.

Aims: Dilated cardiomyopathy (DCM) with arrhythmic phenotype combines phenotypical aspects of DCM and predisposition to ventricular arrhythmias, typical of arrhythmogenic cardiomyopathy. The definition of DCM with arrhythmic phenotype is not universally accepted, leading to uncertainty in the identification of high-risk patients. This study aimed to assess the prognostic impact of arrhythmic phenotype in risk stratification and the correlation of arrhythmic markers with high-risk arrhythmogenic gene variants in DCM patients.

Arrhythmic risk stratification in non-ischaemic dilated cardiomyopathy.

Dilated cardiomyopathy is a primary disease of the heart muscle, which affects relatively young patients with a low comorbidity profile. It is characterized by structural and/or functional abnormalities leading to systolic dysfunction of the left ventricle or of both ventricles, often associated with dilatation, in the absence of an ischaemic, valvular, or pressure overload cause sufficient to explain the phenotype. Although the prognosis of the disease has greatly improved over the last few decades, prognostic stratification remains a fundamental objective, especially about the prediction of potentially life-threatening arrhythmic events.

A case report of isolated cardiac light chain amyloidosis without clinically overt heart failure: an under-recognized presentation.

Background: Cardiac involvement in amyloid light-chain (AL) amyloidosis usually represents a brick in the wall of a multi-system disease. The presence of cardiac deposition of free light chains (FLCs) is the main determinant of survival. Isolated cardiac AL is an uncommon scenario characterized by a challenging diagnostic and therapeutic workup.

Whole-exome sequencing: Clinical characterization of pediatric and adult Italian patients affected by different forms of hereditary cardiovascular diseases.

Background: Hereditary cardiovascular diseases comprise several different entities. In this study, we focused on cardiomyopathies (i.e.

The response to cardiac resynchronization therapy in LMNA cardiomyopathy.

Aims: Cardiac implantable electronic device (CIED) therapy is fundamental to the management of LMNA cardiomyopathy due to the high frequency of atrioventricular block and ventricular tachyarrhythmias. We aimed to define the role of cardiac resynchronization therapy (CRT) in impacting heart failure in LMNA cardiomyopathy.

Methods And Results: From nine referral centres, LMNA cardiomyopathy patients who underwent CRT with available pre- and post-echocardiograms were identified retrospectively.

Activation of PDGFRA signaling contributes to filamin C-related arrhythmogenic cardiomyopathy.

truncating mutations () are prevalent causes of inherited dilated cardiomyopathy (DCM), with a high risk of developing arrhythmogenic cardiomyopathy. We investigated the molecular mechanisms of mutant FLNC in the pathogenesis of arrhythmogenic DCM (a-DCM) using patient-specific induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). We demonstrated that iPSC-CMs from two patients with different mutations displayed arrhythmias and impaired contraction.

Association of Titin Variations With Late-Onset Dilated Cardiomyopathy.

Importance: Dilated cardiomyopathy (DCM) is frequently caused by genetic factors. Studies identifying deleterious rare variants have predominantly focused on early-onset cases, and little is known about the genetic underpinnings of the growing numbers of patients with DCM who are diagnosed when they are older than 60 years (ie, late-onset DCM).

Objective: To investigate the prevalence, type, and prognostic impact of disease-associated rare variants in patients with late-onset DCM.

The Arrhythmic Phenotype in Cardiomyopathy.

In the wide phenotypic spectrum of cardiomyopathies, sudden cardiac death (SCD) has always been the most visible and devastating disease complication. The introduction of implantable cardioverter-defibrillators for SCD prevention by the late 1980s has moved the question from how to whom we should protect from SCD, leaving clinicians with a measure of uncertainty regarding the most reliable option to guide identification of the highest-risk patients. In this review, we will go through all the available evidence in the field of arrhythmic expression and arrhythmic risk stratification in the different phenotypes of cardiomyopathies to provide practical suggestions in daily clinical management.

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.

Prevalence and Evolution of Right Ventricular Dysfunction Among Different Genetic Backgrounds in Dilated Cardiomyopathy.

Background: Titin (TTN)-related dilated cardiomyopathy (DCM) has a higher likelihood of left ventricular reverse remodelling compared with other genetic etiologies. No data regarding the evolution of right ventricular dysfunction (RVD) according to genetic background are available.

Methods: Consecutive 104 DCM patients with confirmed pathogenic genetic variants (51 TTN-related DCM; 53 other genetic DCM) and a control group of 139 patients with negative genetic testing and available follow-up data at 12-24 months were analysed.

High prevalence of subtle systolic and diastolic dysfunction in genotype-positive phenotype-negative relatives of dilated cardiomyopathy patients.

Background: The early diagnosis of genetically determined dilated cardiomyopathy (DCM) could improve the prognosis in mutation carriers. Left ventricular global longitudinal strain (LV GLS) and peak left atrial longitudinal strain (PALS) are promising techniques for the detection of subtle systolic and diastolic dysfunction. We sought to evaluate the prevalence of subtle systolic and diastolic dysfunction by LV GLS and PALS in a cohort of genotype-positive phenotype-negative (GPFN) DCM relatives.

Contemporary survival trends and aetiological characterization in non-ischaemic dilated cardiomyopathy.

Aim: Contemporary survival trends in dilated cardiomyopathy (DCM) are largely unknown. The aim of this study is to investigate clinical descriptors, survival trends and the prognostic impact of aetiological characterization in DCM patients.

Methods And Results: Dilated cardiomyopathy patients were consecutively enrolled and divided into four groups according to the period of enrolment (1978-1984; 1985-1994; 1995-2004; and 2005-2015).

Risk of sudden cardiac death in New York Heart Association class I patients with dilated cardiomyopathy: A competing risk analysis.

Aims: Primary prevention implantable cardioverter defibrillator (ICD) is not generally recommended in New York Heart Association (NYHA) I class patients with dilated cardiomyopathy (DCM). This study sought to assess the competing risk of sudden cardiac death (SCD) in DCM patients with left ventricular ejection fraction (EF) ≤35% and NYHA I class.

Methods: A total of 272 DCM patients with EF ≤35% and NYHA class I-III after ≥3 months of guideline-directed medical therapy were included.

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.