Desmoglein-2 mutations are detected in 5-10% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Endurance training accelerates the development of the ARVC phenotype, leading to earlier arrhythmic events. Homozygous Dsg2 mutant mice develop a severe ARVC-like phenotype. The phenotype of heterozygous mutant (Dsg2mt/wt) or haploinsufficient (Dsg20/wt) mice is still not well understood. To assess the effects of age and endurance swim training, we studied cardiac morphology and function in sedentary one-year-old Dsg2mt/wt and Dsg20/wt mice and in young Dsg2mt/wt mice exposed to endurance swim training. Cardiac structure was only occasionally affected in aged Dsg20/wt and Dsg2mt/wt mice manifesting as small fibrotic foci and displacement of Connexin 43. Endurance swim training increased the right ventricular (RV) diameter and decreased RV function in Dsg2mt/wt mice but not in wild types. Dsg2mt/wt hearts showed increased ventricular activation times and pacing-induced ventricular arrhythmia without obvious fibrosis or inflammation. Preload-reducing therapy during training prevented RV enlargement and alleviated the electrophysiological phenotype. Taken together, endurance swim training induced features of ARVC in young adult Dsg2mt/wt mice. Prolonged ventricular activation times in the hearts of trained Dsg2mt/wt mice are therefore a potential mechanism for increased arrhythmia risk. Preload-reducing therapy prevented training-induced ARVC phenotype pointing to beneficial treatment options in human patients.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a challenging genetic disorder marked by ventricular arrhythmias and sudden cardiac death, particularly in athletes and young adults. Despite its clinical significance, the relative effectiveness and safety of catheter ablation versus conventional management in ARVC are not fully delineated. Objective This study evaluates the efficacy and safety of catheter ablation compared to conventional management in reducing ventricular arrhythmias and improving patient outcomes over five years in ARVC patients. Methods In a retrospective cohort design at Lady Reading Hospital, Peshawar, we analyzed 120 ARVC patients from January 2018 to December 2023. Patients were divided into two groups: those undergoing catheter ablation and those receiving conventional management. Primary outcomes assessed were recurrence of ventricular arrhythmias, procedural complications, hospitalization duration, and mortality rates. Logistic regression was adjusted for demographics and clinical variables. Results Catheter ablation significantly lowered the recurrence of ventricular arrhythmias (20% vs. 55%, p<0.01) and reduced hospital stay duration (4 ± 2 days vs. 7 ± 3 days, p<0.05). A trend toward reduced five-year mortality was observed in the catheter ablation group (5% vs. 15%, p=0.07). Age, New York Heart Association class, and exercise capacity emerged as significant predictors of outcomes. Conclusions Catheter ablation outperforms conventional management in reducing the recurrence of ventricular arrhythmias and hospitalization in ARVC patients, with a promising trend toward enhanced survival. These findings advocate for personalized management strategies in ARVC, highlighting the necessity for further research to establish the long-term benefits of catheter ablation.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC), or more recently known as arrhythmogenic cardiomyopathy (ACM), is an heritable disorder of the myocardium characterized by progressive fibrofatty replacement the heart muscle and risk of ventricular arrhythmias and sudden cardiac death (SCD). We report a case study to demonstrate the role of gene mutation detection in risk stratification for primary prevention of SCD in a young patient diagnosed with ARVC.
METHODS: A 15-year-old Asian (Vietnamese) male patient with no history of documented tachyarrhythmia or syncope and a family history of potential SCD was admitted due to palpitations. Clinical findings and work-up including cardiac magnetic resonance imaging (MRI) were highly suggestive of ARVC. Gene sequencing was performed for SCD risk stratification, during which PKP2 gene mutation was found. Based on the individualized risk stratification, an ICD was implanted for primary prevention of SCD. At 6 months post ICD implantation, the device detected and successfully delivered an appropriate shock to terminate an episode of potentially fatal ventricular arrhythmia. ICD implantation was therefore proven to be appropriate in this patient.
CONCLUSIONS: While gene mutations are known to be an important factor in the diagnosis of ARVC according to the 2010 Task Force Criteria and recent clinical guidelines, their role in risk stratification of SCD remains controversial. Our case demonstrated that when used with other clinical factors and family history, this information could be helpful in identifying appropriate indication for ICD implantation.

Arrhythmogenic cardiomyopathy (ACM) is an umbrella term encompassing a wide variety of overlapping hereditary and nonhereditary disorders that can result in malignant ventricular arrhythmias and sudden cardiac death. Cardiac MRI plays a critical role in accurate diagnosis of various ACM entities and is increasingly showing promise in risk stratification that can further guide management particularly in decisions regarding use of implantable cardioverter defibrillator. Genotyping plays an important role in cascade testing but challenges remain due to incomplete penetrance and wide phenotypic variability of ACM as well as the presence of gene-elusive cases.

Cardiomyopathies remain one of the most common inherited cardiac diseases in both human and veterinary patients. To date, well over 100 mutated genes are known to cause cardiomyopathies in humans with only a handful known in cats and dogs. This review highlights the need and use of personalized one-health approaches to cardiovascular case management and advancement in pharmacogenetic-based therapy in veterinary medicine. Personalized medicine holds promise in understanding the molecular basis of disease and ultimately will unlock the next generation of targeted novel pharmaceuticals and aid in the reversal of detrimental effects at a molecular level.

UNASSIGNED: The right ventricle can be susceptible to pathologic alterations with exercise. This can cause changes to the ECG. Our aim was to identify the electrocardiographic phenotype of exercise induced (ExI) arrhythmogenic cardiomyopathy (ACM).
UNASSIGNED: A retrospective analysis of ECGs at rest, peak exercise and 1 min of recovery in four groups of individuals was performed: Arrhythmogenic Cardiomyopathy with genetic confirmation (Gen-ACM; n = 16), (genetically negative) ExI-ACM (n = 15), control endurance athletes (End; n = 16) and sedentary individuals (Sed; n = 16). The occurrence of ventricular arrhythmias (VA) and, at each stage, QRS duration, Terminal Activation Delay (TAD), the ratio of the sum of the QRS durations in the right precordials (V1-V3) over that in the left precordials (V4-V6; R/L duration ratio), the presence of complete RBBB and T-wave inversion (TWI) beyond lead V2 were evaluated.
UNASSIGNED: At rest, complete RBBB was exclusively found in Gen-ACM (6%) and ExI-ACM (13%). No epsilon waves were identified. TWI beyond V2 was uniquely present in Gen-ACM (73%) and ExI-ACM (38%; p < 0.001). VA was present in Gen-ACM (88%); ExI-ACM (80%), End (25%) and Sed (19%; p < 0.001). The presence of R/L duration ratio of >1.2 and TAD ≥ 55 ms were not significantly different over the four groups (p = 0.584 and p = 0.218, respectively). At peak exercise the most striking finding was a significant decrease of the R/L duration ratio in individuals with ACM, which was the result of lateral precordial QRS prolongation.
UNASSIGNED: ExI-ACM shares important ECG-features with Gen-ACM, suggesting a similar underlying pathogenesis regardless of the presence or absence of desmosomal mutations.

暂无摘要。

Arrhythmogenic Right Ventricular cardiomyopathy (ARVC) is an inherited cardiac muscle disease linked to genetic deficiency in components of the desmosomes. The disease is characterized by progressive fibro-fatty replacement of the right ventricle, which acts as a substrate for arrhythmias and sudden cardiac death. The molecular mechanisms underpinning ARVC are largely unknown. Here we propose a mathematical model for investigating the molecular dynamics underlying heart remodeling and the loss of cardiac myocytes identity during ARVC. Our methodology is based on three computational models: firstly, in the context of the Wnt pathway, we examined two different competition mechanisms between β-catenin and Plakoglobin (PG) and their role in the expression of adipogenic program. Secondly, we investigated the role of RhoA-ROCK pathway in ARVC pathogenesis, and thirdly we analyzed the interplay between Wnt and RhoA-ROCK pathways in the context of the ARVC phenotype. We conclude with the following remark: both Wnt/β-catenin and RhoA-ROCK pathways must be inactive for a significant increase of PPARγ expression, suggesting that a crosstalk mechanism might be responsible for mediating ARVC pathogenesis.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disease in children, and can lead to sudden cardiac death (SCD). Propafenone is classIC antiarrhythmic medication, and its side effects include cardiovascular compromise in the form of hypotension, bradycardia, ventricular dysrhythmias, QRS widening, and heart block. Propafenone has been reported causing QRS widening, but rarely in children. In this article, we presented a boy diagnosed with ARVC who meets diagnosis criteria based on typical symptoms, electrocardiograph (ECG), echocardiography (Echo), cardiac magnetic resonance imaging (CMRI), sudden death of first family member, and genetic mutation in desmosomal DSG2 gene. Antiarrhythmic drugs have been used for treating patients with ARVC, by eliminating or decreasing the occurring frequency of arrhythmias. As his ECG showed frequent premature ventricular contractions (PVC), he was prescribed with oral propafenone. One day after the drug treatment, he presented dizziness accompanied with significant QRS widening in ECG. His dizziness was improved when Propafenone dose was reduced, and resolved after sotalol replacement, with ECG recovered to nearly normal state of QRS. Propafenone may lead to QRS widening and increase the risk of ventricular tachycardia, and it may not reduce ARVC associated mortality. This report may serve as a precaution for clinicians when providing cares for ARVC patients.

Cardiomyopathies are diseases of heart muscle, a significant percentage of which are genetic in origin. Cardiomyopathies can be classified as dilated, hypertrophic, restrictive, arrhythmogenic right ventricular or left ventricular non-compaction, although mixed morphologies are possible. A subset of neuromuscular disorders, notably Duchenne and Becker muscular dystrophies, are also characterized by cardiomyopathy aside from skeletal myopathy. The global burden of cardiomyopathies is certainly high, necessitating further research and novel therapies. Genome editing tools, which include zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR) systems have emerged as increasingly important technologies in studying this group of cardiovascular disorders. In this review, we discuss the applications of genome editing in the understanding and treatment of cardiomyopathy. We also describe recent advances in genome editing that may help improve these applications, and some future prospects for genome editing in cardiomyopathy treatment.