Management Of Arrhythmogenic Right Ventricular Cardiomyopathy Research Articles

Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) encompasses a group of conditions characterized by right ventricular fibrofatty infiltration, with a predominant arrhythmic presentation. First described in the late 1970s and early 1980s, it is now frequently recognized to have biventricular involvement. The prevalence is ∼1:2,000 to 1:5,000, depending on geographic location, and it has a slight male predominance. The diagnosis of ARVC is determined on the basis of fulfillment of task force criteria incorporating electrophysiological parameters, cardiac imaging findings, genetic factors, and histopathologic features. Risk stratification of patients with ARVC aims to identify those who are at increased risk of sudden cardiac death or sustained ventricular tachycardia. Factors including age, sex, electrophysiological features, and cardiac imaging investigations all contribute to risk stratification. The current management of ARVC includes exercise restriction, β-blocker therapy, consideration for implantable cardioverter-defibrillator insertion, and catheter ablation. This review summarizes our current understanding of ARVC and provides clinicians with a practical approach to diagnosis and management.

Integrin β1D Deficiency-Mediated RyR2 Dysfunction Contributes to Catecholamine-Sensitive Ventricular Tachycardia in Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart disease characterized by fatty infiltration, life-threatening arrhythmias, and increased risk of sudden cardiac death. The guideline for management of ARVC in patients is to improve quality of life by reducing arrhythmic symptoms and to prevent sudden cardiac death. However, the mechanism underlying ARVC-associated cardiac arrhythmias remains poorly understood. Using protein mass spectrometry analyses, we identified that integrin β1 is downregulated in ARVC hearts without changes to Ca2+-handling proteins. As adult cardiomyocytes express only the β1D isoform, we generated a cardiac specific β1D knockout mouse model and performed functional imaging and biochemical analyses to determine the consequences of integrin β1D loss on function in the heart in vivo and in vitro. Integrin β1D deficiency and RyR2 Ser-2030 hyperphosphorylation were detected by Western blotting in left ventricular tissues from patients with ARVC but not in patients with ischemic or hypertrophic cardiomyopathy. Using lipid bilayer patch clamp single channel recordings, we found that purified integrin β1D protein could stabilize RyR2 function by decreasing RyR2 open probability, mean open time, and increasing mean close time. Also, β1D knockout mice exhibited normal cardiac function and morphology but presented with catecholamine-sensitive polymorphic ventricular tachycardia, consistent with increased RyR2 Ser-2030 phosphorylation and aberrant Ca2+ handling in β1D knockout cardiomyocytes. Mechanistically, we revealed that loss of DSP (desmoplakin) induces integrin β1D deficiency in ARVC mediated through an ERK1/2 (extracellular signal-regulated kinase 1 and 2)-fibronectin-ubiquitin/lysosome pathway. Our data suggest that integrin β1D deficiency represents a novel mechanism underlying the increased risk of ventricular arrhythmias in patients with ARVC.

Multiparametric Approach to Arrhythmogenic Cardiomyopathy: Clinical, Instrumental, and Lifestyle Indications

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder with an autosomal dominant inheritance and incomplete penetrance. It predominantly affects the right ventricle (RV), predisposing to the origin of ventricular arrhythmias and sudden death (SD). The structural basis of the disease consists of the progressive loss of myocardium with fibro-adipose replacement. ARVC is a “desmosomes” disease involving mutations of proteins such as placoglobin, desmoplachine, placophylline, desmoglein, and desmocollin. In the “classical” form, the disease mainly implicates the RV chamber, while the left ventricle (LV) is involved in advanced stages. Genotype-phenotype correlation studies have identified some phenotypic variants characterized by an early participation of the LV, which can proceed in parallel toward the two ventricles (“biventricular” variant) or prevails over the RV (variant to “left dominance”). These data led to the evolution of the initial definition of ARVC, which is currently considered a genetic disease of both ventricles and, therefore, deserves the denomination “arrhythmogenic cardiomyopathy”. Many aspects of diagnosis, treatment, and indications for a correct lifestyle are important in sports medicine. This paper will discuss the clinical management of ARVC, with particular reference to diagnosis, risk stratification, therapy, and indications for physical activity.

Cardiocutaneous syndrome (Naxos disease) in a Bangladeshi boy

Naxos disease is a rare autosomal recessive form of arrhythmogenic right ventricular cardiomyopathy (ARVC) with woolly hair and palmoplantar keratoderma. The cardiomyopathy presents by adolescence with syncope, ventricular tachycardia (VT) of left bundle branch block (LBBB) morphology, and/or ventricular fibrillation. The diagnosis and management of ARVC are at present in evolution; the recently published modified Task Force Criteria for diagnosis and International Task Force consensus statement for treatment of ARVC will hopefully bring about uniformity in recognition and management of Naxos disease as well. Here, typical phenotype and diagnostic work up have been presented in a Bangladeshi boy with the Cardiocutaneous syndrome.

2015 update on the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy.

This review will discuss the recent advances in the diagnosis and management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Since the first detailed clinical description of the disease in 1982, we have learned much about the genetics, pathophysiology, diagnosis, and management of ARVC. We now appreciate that pathogenic mutations in desmosomal genes are the most common genetic finding. Although the right ventricle is mostly affected, left ventricular involvement is being increasingly recognized. Electrical instability precipitating sudden cardiac death often presents before structural abnormalities, and therefore early accurate diagnosis is of utmost importance. The broad spectrum of phenotypic variation, age-related penetrance, and lack of a definitive diagnostic test make the clinical diagnosis challenging. The diagnosis is made by fulfilling the 2010 Task Force criteria. Today, genetic testing and cardiac MRI play an important role in the diagnosis. Implantable cardioverter defibrillator implantation is the only lifesaving therapy available today for a subset of patients. In patients with recurrent ventricular arrhythmias, epicardial catheter ablation has demonstrated improved outcomes compared with endocardial ablation. Exercise restriction may delay the progression of disease. ARVC is predominantly associated with mutations in desmosomal genes with incomplete penetrance and variable expressivity. Ventricular electrical instability is the hallmark of ARVC, often occurring before structural abnormalities. Goals in the evaluation and management of ARVC are early diagnosis, risk stratification for sudden cardiac death, minimizing ventricular arrhythmias, and delaying the progression of disease.

Sudden killer

Sudden killer