Epigenetic mechanisms underlying the beneficial effects of cardiac rehabilitation. An overview from the working groups of "cellular and molecular biology of the heart" and "cardiac rehabilitation and cardiovascular prevention" of the Italian Society of Cardiology (SIC).

The benefits of cardiac rehabilitation (CR) have been demonstrated in patients after myocardial infarction (MI), and in patients with chronic heart failure (HF). The core components of the CR program include improvement in exercise tolerance and optimization of coronary risk factors (i.e.

The 'Padua classification' of cardiomyopathies into three groups: hypertrophic/restrictive, dilated/hypokinetic, and scarring/arrhythmogenic.

The newly proposed classification of cardiomyopathies, referred to as 'the Padua Classification', is based on both pathobiological basis (genetics, molecular biology, and pathology) and clinical features (morpho-functional and structural ventricular remodelling as evidenced by cardiac magnetic resonance). Cardiomyopathies are grouped into tree main categories and characterized by a designation combining both 'anatomical' and 'functional' features: hypertrophic/restrictive, dilated/hypokinetic, and scarring/arrhythmogenic; each cardiomyopathy group includes either genetic or non-genetic aetiologic variants. This novel approach aims to enhance the diagnostic accuracy and to support 'disease-specific' therapeutic strategies, with the objective to improve patient management and outcome.

Risk stratification in arrhythmogenic cardiomyopathy: scoring or personalized medicine?

Almost 40 years after the description of arrhythmogenic cardiomyopathy (ACM), arrhythmic risk stratification remains central to patient management. Antiarrhythmic therapy may involve the use of antiarrhythmic drugs as well as invasive tools such as catheter ablation, with the implantation of an implantable cardioverter defibrillator being of utmost importance. Given the wide phenotypic variability of ACM, the first step in arrhythmic risk stratification requires a thorough assessment of clinical, morphological, and electrical parameters.

Arrhythmic Risk Stratification of Carriers of Filamin C Truncating Variants.

Importance: Filamin C truncating variants (FLNCtv) are a rare cause of cardiomyopathy with heterogeneous phenotypic presentations. Despite a high incidence of life-threatening ventricular arrhythmias and sudden cardiac death (SCD), reliable risk predictors to stratify carriers of FLNCtv are lacking.

Objective: To determine factors predictive of SCD/major ventricular arrhythmias (MVA) in carriers of FLNCtv.

The "Padua classification" of cardiomyopathies: Combining pathobiological basis and morpho-functional remodeling.

Over the last 20 years, the scientific progresses in molecular biology and genetics in combination with the increasing use in the clinical setting of contrast-enhanced cardiac magnetic resonance (CMR) for morpho-functional imaging and structural myocardial tissue characterization have provided important new insights into our understanding of the distinctive aspects of cardiomyopathy, regarding both the genetic and biologic background and the clinical phenotypic features. This has led to the need of an appropriate revision and upgrading of current nosographic framework and pathobiological categorization of heart muscle disorders. This article proposes a new definition and classification of cardiomyopathies that rely on the combination of the distinctive pathobiological basis (genetics, molecular biology and pathology) and the clinical phenotypic pattern (morpho-functional and structural features), leading to the proposal of three different disease categories, each of either genetic or non-genetic etiology and characterized by a combined designation based on both "anatomic" and "functional" features, i.

In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.

Arrhythmogenic cardiomyopathy (AC) is a hereditary cardiac disorder characterized by the gradual replacement of cardiomyocytes with fibrous and adipose tissue, leading to ventricular wall thinning, chamber dilation, arrhythmias, and sudden cardiac death. Despite advances in treatment, disease management remains challenging. Animal models, particularly mice and zebrafish, have become invaluable tools for understanding AC's pathophysiology and testing potential therapies.

Clinical Insights in RNA-Binding Protein Motif 20 Cardiomyopathy: A Systematic Review.

Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and heart transplantation (HTx), with genetic factors playing a significant role. In recent years, the RNA-binding protein motif 20 (), which affects the gene splicing of various proteins with different cellular functions, was identified as the first DCM gene with regulatory properties. Variants of have been associated with severe forms of DCM.

Phenotype and Clinical Outcomes in Desmin-Related Arrhythmogenic Cardiomyopathy.

Background: Desmin (DES) pathogenic variants cause a small proportion of arrhythmogenic cardiomyopathy (ACM). Outcomes data on DES-related ACM are scarce.

Objectives: This study sought to provide information on the clinical phenotype and outcomes of patients with ACM caused by pathogenic variants of the DES gene in a multicenter cohort.

Mitophagy modulation for the treatment of cardiovascular diseases.

Background: Defects of mitophagy, the selective form of autophagy for mitochondria, are commonly observed in several cardiovascular diseases and represent the main cause of mitochondrial dysfunction. For this reason, mitophagy has emerged as a novel and potential therapeutic target.

Methods: In this review, we discuss current evidence about the biological significance of mitophagy in relevant preclinical models of cardiac and vascular diseases, such as heart failure, ischemia/reperfusion injury, metabolic cardiomyopathy and atherosclerosis.

Phenotypic Expression and Clinical Outcomes in Patients With Arrhythmogenic Cardiomyopathies.

Background: In recent years, it has become evident that arrhythmogenic cardiomyopathy (ACM) displays a wide spectrum of ventricular involvement. Furthermore, the influence of various clinical phenotypes on the prognosis of the disease is currently being assessed.

Objectives: The purpose of this study was to evaluate the impact of phenotypic expression in ACM on patient outcomes.

A New Inherited Syndrome Causing Sudden Cardiac Death with Distinct ST-Segment Depression and Ankyrin-2-Mutation.

Introduction: Sudden cardiac death (SCD) is a serious threat. In individuals under the age of 35 years sudden arrhythmic death is the most frequent cause. In younger persons, genetically determined cardiac diseases (eg, cardiomyopathies and ion-channel diseases) account for an important proportion of these cases.

A novel DSP zebrafish model reveals training- and drug-induced modulation of arrhythmogenic cardiomyopathy phenotypes.

Arrhythmogenic cardiomyopathy (AC) is an inherited disorder characterized by progressive loss of the ventricular myocardium causing life-threatening ventricular arrhythmias, syncope and sudden cardiac death in young and athletes. About 40% of AC cases carry one or more mutations in genes encoding for desmosomal proteins, including Desmoplakin (Dsp). We present here the first stable Dsp knock-out (KO) zebrafish line able to model cardiac alterations and cell signalling dysregulation, characteristic of the AC disease, on which environmental factors and candidate drugs can be tested.

Desmosomal Arrhythmogenic Cardiomyopathy: The Story Telling of a Genetically Determined Heart Muscle Disease.

The history of arrhythmogenic cardiomyopathy (AC) as a genetically determined desmosomal disease started since the original discovery by Lancisi in a four-generation family, published in 1728. Contemporary history at the University of Padua started with Dalla Volta, who haemodynamically investigated patients with "auricularization" of the right ventricle, and with Nava, who confirmed familiarity. The contemporary knowledge advances consisted of (a) AC as a heart muscle disease with peculiar electrical instability of the right ventricle; (b) the finding of pathological substrates, in keeping with a myocardial dystrophy; (c) the inclusion of AC in the cardiomyopathies classification; (d) AC as the main cause of sudden death in athletes; (e) the discovery of the culprit genes coding proteins of the intercalated disc (desmosome); (f) progression in clinical diagnosis with specific ECG abnormalities, angiocardiography, endomyocardial biopsy, 2D echocardiography, electron anatomic mapping and cardiac magnetic resonance; (g) the discovery of left ventricular AC; (h) prevention of SCD with the invention and application of the lifesaving implantable cardioverter defibrillator and external defibrillator scattered in public places and playgrounds as well as the ineligibility for competitive sport activity for AC patients; (i) genetic screening of the proband family to unmask asymptomatic carriers.

Chest pain in cardiac amyloidosis: occurrence, causes and prognostic significance.

Background: Chest pain is experienced by patients with cardiac amyloidosis (CA), but a systematic investigation of its frequency, underlying etiologies and clinical significance is lacking.

Methods: Clinical, echocardiographic, laboratory characteristics, available coronary arteries imaging and endomyocardial biopsy (EMB) findings of 174 patients with CA (n = 104 with transthyretin, ATTR; n = 70 with light chains, AL) were analyzed.

Results: Chest pain was reported in 66 (38%) CA patients.

A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331).

Is Congenital Muscular Mitral-Aortic Discontinuity Another Feature of Obstructive Hypertrophic Cardiomyopathy? A Pathology Validation Study.

Hypertrophic cardiomyopathy (HCM) is an inherited myocardial disease at risk of sudden cardiac death and heart failure, even requiring heart transplantation. A "muscular mitral-aortic discontinuity" has been reported during surgery in the obstructive form. We aimed to validate these findings through pathological analysis of HCM heart specimens from the cardiovascular pathology tissue registry.