Exercise testing for long-term follow-up in arrhythmogenic right ventricular cardiomyopathy

Objectives

We investigated arrhythmia, electrocardiography and physical work capacity (PWC) in the follow-up of ARVC.

Right ventricular outflow tract tachycardia in children

OBJECTIVE: To assess the clinical spectrum of right ventricular outflow tract tachycardia and its management in children. STUDY DESIGN: Five centers identified patients for retrospective review. Patients (age <18 years) demonstrating ventricular tachycardia with an inferior axis and left bundle branch block were included. Patients with structural heart disease, myocarditis, cardiomyopathy, or long QT syndrome were excluded. Demographics, clinical presentation, investigations, and treatment were analyzed. Holter data were used to quantify ectopy. RESULTS: Patients (n = 48) were referred for evaluation of incidental findings (39/48), near syncope or syncope (7/48), or other (2/48). Investigations included magnetic resonance imaging (51%), endomyocardial biopsy (25%), and angiography (23%). Medical treatment was initiated in 26 of the 48 patients. The most common indications for treatment were frequent ectopy and symptoms. Medical treatment (P <.007) and observation alone (P <.02) were both associated with a reduction in ectopy. Symptoms persisted in 3 of 13 patients who were treated medically and in all untreated patients. At follow-up, there were no deaths and no difference in ectopy (P <.46) between patients who were treated medically and patients who were observed. Ablation was attempted in 6 of the 48 patients (successful in 4/6). CONCLUSION: The clinical spectrum and management of right ventricular outflow tract tachycardia in children are diverse. Both medical therapy and observation alone were associated with a reduction in ectopy.     

Etiopathogenesis of arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterised by progressive fibro-fatty replacement of right ventricular myocardium. Earlier studies described ARVC as non-inflammatory, non-coronary disorder associated with arrhythmias, heart failure and sudden death due to functional exclusion of the right ventricle. Molecular genetic studies have identified nine different loci associated with ARVC; accordingly each locus is implicated for each type of ARVC (ARVC1–ARVC9). So far five genes have been identified as containing pathogenic mutations for ARVC. Though mutations in each of the gene/s indicate disruption of different pathways leading to the condition, the exact pathogenesis of the condition is still obscure. This review tries to understand the pathogenesis of the condition by examining the individual proteins implicated and relate them to the pathways that could play a role in the aetiology of the condition. Cardiac ryanodine receptor (RYR-2), which regulates intra-cellular Ca²⁺ concentration by releasing Ca²⁺ reserves from the sarcoplasmic reticulum (SR), was the first gene for ARVC. The mutation in this gene is believed to disrupt coupled gating of RYR-2, causing after-depolarisation, leading to arrhythmias followed by structural changes due to altered intra-cellular Ca²⁺ levels. Three other genes implicated for ARVC, plakoglobin (Naxos disease), desmoplakin (ARVC8) and plakophilin (ARVC9) have prompted the speculation that ARVC is primarily a disease of desmosomes. But identification of TGF-3 for ARVC1 and the role of all these three genes (plakoglobin, desmoplakin and plakophilin) in cardiac morphogenesis indicate some kind of signal-transducing pathway disruption in the condition. The finding that ARVC as a milder form of Uhls anomaly indicates similar ontogeny for the condition. Further, discovery of apoptotic cells in the autopsy of the right ventricular myocardium of ARVC patients does indicate a common pathway for different types of ARVCs, which is more specific for the right ventricular myocardium involving desmosomal plaque proteins, growth factors and Ca²⁺ receptors.     

Genetic testing in cardiovascular disease

Genetic testing is increasingly becoming possible for diagnosis, susceptibility testing, and prognostication in cardiovascular medicine. The practicing cardiologist, therefore, needs to be familiar with the clinical utilities and limitations of genetic testing. This review explores the major approaches to genetic testing and issues in test interpretation. Specific applications to cardiovascular diseases, including coronary artery disease, cardiomyopathies, cardiac arrhythmias, and pulmonary arterial hypertension are discussed.     

Female Hunter syndrome caused by a single mutation and familial XCI skewing: implications for other X-linked disorders

Familial X-chromosome inactivation (XCI) skewing was investigated in a family in which a female mucopolysaccharidosis type II (MPS II) (Hunter syndrome, an X-linked genetic disease) occurred. Among eight related females aged under 60 years from three generations who were tested, four revealed a non-random pattern of XCI. Detailed genetic analysis failed to find mutations in genes that were previously reported as important for the XCI process. Haplotype analysis excluded linkage of non-random XCI with genes localized on the X-chromosome. We propose that analysis of the XCI pattern should be taken into consideration when assessing risk factors for X-linked recessive genetic disorders.     

Clinical course of arrhythmogenic right ventricular cardiomyopathy with end-stage heart failure and outcome after heart transplantation

BackgroundFew data exist on the characteristics and outcomes of patients with arrhythmogenic right ventricular cardiomyopathy and advanced heart failure who undergo heart transplantation.AimTo explore the pretransplant course and outcomes of patients with arrhythmogenic right ventricular cardiomyopathy after heart transplantation.MethodsThis observational retrospective monocentric study included all consecutive patients with arrhythmogenic right ventricular cardiomyopathy who underwent heart transplantation during a 13-year period (2006–2019) at Pitié-Salpêtrière University Hospital (Paris).ResultsA total of 23 patients with arrhythmogenic right ventricular cardiomyopathy underwent heart transplantation between 2006 and 2019. The median time from diagnosis to heart transplantation was 9 years, and the median age at transplantation was 50 years. At diagnosis, half of the patients had left ventricular dysfunction, 59% had extensive T-wave inversion and 43% had a history of sustained ventricular tachycardia. Only five patients were involved in intensive sport activity. Indications for heart transplantation were end-stage biventricular dysfunction in 13 patients, end-stage right ventricular heart failure in seven and electrical storm in three. Only three patients had pulmonary hypertension, and half of the patients had atrial arrhythmias. The survival rate 1 year after heart transplantation was 74% (95% confidence interval 53–88%). Eight patients experienced primary graft dysfunction needing extracorporeal membrane oxygenation.ConclusionsPatients with arrhythmogenic right ventricular cardiomyopathy who eventually needed heart transplantation mostly exhibited extended disease with biventricular dysfunction at diagnosis. Intensive sport activity did not seem to be a major determinant. Advanced heart failure usually occurred late in the course of the disease. Primary graft dysfunction after heart transplantation was frequent, and should be anticipated. Additional data are needed to identify the optimal timing for heart transplantation and predictors of end-stage heart failure in patients with arrhythmogenic right ventricular cardiomyopathy.