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.

The IAAM LTBP4 Haplotype is Protective Against Dystrophin-Deficient Cardiomyopathy.

Background: Dilated cardiomyopathy (DCM) is a major complication of, and leading cause of mortality in Duchenne muscular dystrophy (DMD). Its severity, age at onset, and rate of progression display wide variability, whose molecular bases have been scarcely elucidated. Potential DCM-modifying factors include glucocorticoid (GC) and cardiological treatments, DMD mutation type and location, and variants in other genes.

Clinical characteristics and outcome of end stage hypertrophic cardiomyopathy: Role of age and heart failure phenotypes.

Background: A minority of patients with hypertrophic cardiomyopathy (HCM) presents advanced heart failure (HF) during their clinical course, in the context of left ventricular (LV) remodeling with reduced LV ejection fraction (LVEF), or of severe diastolic dysfunction without impaired LVEF. Aim of this study was to describe a multicentric end stage (ES) HCM population and analyze clinical course and outcome among its different phenotypes.

Methods: Data of all HCM patients from 7 Italian referral centres were retrospectively evaluated.

Real-world candidacy to mavacamten in a contemporary hypertrophic obstructive cardiomyopathy population.

Aims: In the EXPLORER-HCM trial, mavacamten reduced left ventricular outflow tract obstruction (LVOTO) and improved functional capacity of symptomatic hypertrophic obstructive cardiomyopathy (HOCM) patients. We sought to define the potential use of mavacamten by comparing real-world HOCM patients with those enrolled in EXPLORER-HCM and assessing their eligibility to treatment.

Methods And Results: We collected information on HOCM patients followed up at 25 Italian HCM outpatient clinics and with significant LVOTO (i.

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.

Strength of clinical indication and therapeutic impact of the implantable cardioverter defibrillator in patients with hypertrophic cardiomyopathy.

Background: The implantable cardioverter defibrillator(ICD) has revolutionized the management of patients with hypertrophic cardiomyopathy (HCM) at risk of sudden cardiac death (SCD). However, the identification of ideal candidates remains challenging. We aimed to describe the long-term impact of the ICD for primary prevention in patients with HCM based on stringent (high SCD risk) vs lenient indications (need for pacing/personal choice).

Hypertrophic Cardiomyopathy and Primary Restrictive Cardiomyopathy: Similarities, Differences and Phenocopies.

Hypertrophic cardiomyopathy (HCM) and primary restrictive cardiomyopathy (RCM) have a similar genetic background as they are both caused mainly by variants in sarcomeric genes. These "sarcomeric cardiomyopathies" also share diastolic dysfunction as the prevalent pathophysiological mechanism. Starting from the observation that patients with HCM and primary RCM may coexist in the same family, a characteristic pathophysiological profile of HCM with restrictive physiology has been recently described and supports the hypothesis that familiar forms of primary RCM may represent a part of the phenotypic spectrum of HCM rather than a different genetic cardiomyopathy.

Evaluation of mexiletine effect on conduction delay and bradyarrhythmic complications in patients with myotonic dystrophy type 1 over long-term follow-up.

Background: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder characterized by progressive cardiac conduction impairment, arrhythmias, and sudden death. Mexiletine is a sodium channel blocker drug used by patients with DM1 for treatment of myotonia, even though definitive proof of its safety over long-term follow-up is lacking.

Objective: The purpose of this study was to assess the impact of mexiletine for treatment of neurological symptoms on the composite endpoint of significant electrocardiogram modification (new onset or worsening of atrioventricular [AV] or intraventricular conduction delay) and bradyarrhythmic complications requiring pacemaker (PM) implantation (advanced AV block, symptomatic sinus pause >3 seconds).

The clinical spectrum of -related myopathy.

Objective: To identify and characterize patients with calsequestrin 1 ()-related myopathy.

Methods: Patients selected according to histopathologic features underwent genetic screening. mutated patients were clinically evaluated and underwent muscle MRI.

Muscle MRI and functional outcome measures in Becker muscular dystrophy.

Becker muscular dystrophy (BMD) is a neuromuscular disorder allelic to Duchenne muscular dystrophy (DMD), caused by in-frame mutations in the dystrophin gene, and characterized by a clinical progression that is both milder and more heterogeneous than DMD. Muscle magnetic resonance imaging (MRI) has been proposed as biomarker of disease progression in dystrophinopathies. Correlation with clinically meaningful outcome measures such as North Star Ambulatory Assessment (NSAA) and 6 minute walk test (6MWT) is paramount for biomarker qualification.

Accuracy of the ECG for differential diagnosis between hypertrophic cardiomyopathy and athlete's heart: comparison between the European Society of Cardiology (2010) and International (2017) criteria.

Background: Interpretation of the athlete's ECG is based on differentiation between benign ECG changes and potentially pathological abnormalities. The aim of the study was to compare the 2010 European Society of Cardiology (ESC) and the 2017 International criteria for differential diagnosis between hypertrophic cardiomyopathy (HCM) and athlete's heart.

Methods: The study populations included 200 patients with HCM and 563 athletes grouped as follows: 'group 1', including normal ECG and isolated increase of QRS voltages, which are considered non-pathologic according to ESC and International criteria; 'group 2', including left atrial enlargement or left axis deviation in isolation and Q-waves with an amplitude ≥4 mm but <25% of the ensuing R-wave and a duration <0.

Co-inheritance of mutations associated with arrhythmogenic cardiomyopathy and hypertrophic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) and hypertrophic cardiomyopathy (HCM) are genetically and phenotypically distinct disorders of the myocardium. Here we describe for the first time co-inheritance of mutations in genes associated with ACM or HCM in two families with recurrence of both cardiomyopathies. Among the double heterozygotes for mutations in desmoplakin (DSP) and myosin binding protein C (MYBPC3) genes identified in Family A, two were diagnosed with ACM and two with HCM.

Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies.

We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21).

Electrocardiographic anterior T-wave inversion in athletes of different ethnicities: differential diagnosis between athlete's heart and cardiomyopathy.

Aims: Anterior T-wave inversion (TWI) is a recognized variant in athletes of African/Afro Caribbean origin and some endurance athletes; however, the presence of this specific repolarization anomaly also raises the possibility of cardiomyopathy. The differentiation between physiological adaptation and cardiomyopathy may be facilitated by examining other repolarization parameters, notably the J-point and the ST-segment.

Methods And Results: We compared the electrocardiogram pattern of anterior TWI in a series of 80 healthy athletes (median age 21 years, 75% males); 95 patients with hypertrophic cardiomyopathy (HCM) (median age 46 years, 75% males), including 26 affected athletes; and 58 patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) (median age 32 years, 71% males), including 9 affected athletes.

Genetic Modifiers of Duchenne Muscular Dystrophy and Dilated Cardiomyopathy.

Objective: Dilated cardiomyopathy (DCM) is a major complication and leading cause of death in Duchenne muscular dystrophy (DMD). DCM onset is variable, suggesting modifier effects of genetic or environmental factors. We aimed to determine if polymorphisms previously associated with age at loss of independent ambulation (LoA) in DMD (rs28357094 in the SPP1 promoter, rs10880 and the VTTT/IAAM haplotype in LTBP4) also modify DCM onset.

Is Internet use associated with anxiety in patients with and at risk for cardiomyopathy?

Objective: The aim of the study was to determine the relation between online health information seeking behavior and anxiety level among a sample of patients with manifested cardiomyopathy or at risk for cardiomyopathy.

Methods: The research is a cross-sectional study conducted among 104 patients with cardiomyopathy diagnosis and patients at risk for cardiomyopathy. Patients completed 3 different questionnaires: Use of Internet Health Information questionnaire about the use of Internet, Short Form SF-12 items questionnaire on quality of life, and State-Trait Anxiety Inventory measuring general anxiety levels.

A founder MYBPC3 mutation results in HCM with a high risk of sudden death after the fourth decade of life.

Background: Mutations in the cardiac myosin binding protein C (MYBPC3) gene account for a significant proportion of patients affected with hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the penetrance and the impact of a frequent founder MYBPC3 mutation on HCM clinical expression and prognosis.

Methods And Results: Mutation screening of MYBPC3 gene was performed in 97 HCM probands.

Clinical meaning of isolated increase of QRS voltages in hypertrophic cardiomyopathy versus athlete's heart.

Recent consensus documents have provided modern criteria for interpretation of the athlete's ECG, which are based on a better definition of physiological versus abnormal ECG changes. The aim of these modern criteria is to lower the traditionally high number of false positives and to reduce unnecessary and expensive investigations, maintaining the sensitivity for identification of cardiac diseases at risk of sudden cardiac death during sports such as hypertrophic cardiomyopathy (HCM). This article reviews the published studies regarding the ECG changes associated with HCM ("pathologic hypertrophy") and athlete's heart ("physiologic hypertrophy"), with particular reference to the prevalence and clinical significance of the ECG pattern of isolated increase of QRS voltages.

Impact of the presence and amount of myocardial fibrosis by cardiac magnetic resonance on arrhythmic outcome and sudden cardiac death in nonischemic dilated cardiomyopathy.

Background: Current risk stratification for sudden cardiac death (SCD) in nonischemic dilated cardiomyopathy (NIDC) relies on left ventricular (LV) dysfunction, a poor marker of ventricular electrical instability. Contrast-enhanced cardiac magnetic resonance has the ability to accurately identify and quantify ventricular myocardial fibrosis (late gadolinium enhancement [LGE]).

Objective: To evaluate the impact of the presence and amount of myocardial fibrosis on arrhythmogenic risk prediction in NIDC.