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Purpose of Review: This review highlights the current lack of disease specific therapies available for arrhythmogenic cardiomyopathy (ACM) and explores recent new advances toward novel genotype specific therapies. Recent Findings: Although our understanding of ACM genetics has grown, current therapies are largely based on the general treatment strategies of arrhythmias and heart failure that do not target the diverse underlying pathogenic causes of ACM. Recently, there have been several efforts toward genotype-specific targeted therapies including a small molecule inhibitor for LMNA cardiomyopathy, three distinct gene replacement therapy approaches for PKP2 cardiomyopathy, as well as early work with base editing and prime editing on RBM20 cardiomyopathy. Summary: There is currently a lack of ACM-specific therapies with minimal disease modifying treatments. Advances in gene replacement and editing offer hope for promising novel genotype-specific therapies with the goal of reversing the underlying disease process. [ABSTRACT FROM AUTHOR]

Key points Atrial arrhythmias occur in 20–40% of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and are associated with an increased risk of sustained ventricular arrhythmias and inappropriate implantable cardioverter‐defibrillator shocks. The pathophysiology of atrial arrhythmias in ARVC remains unclear. Most cases of gene‐positive ARVC are linked to pathogenic variants in the desmosomal gene plakophilin‐2 (PKP2). Here, we test the hypothesis that loss of PKP2 expression leads to pro‐arrhythmic changes in atrial cardiomyocytes. Atrial cells/tissue were obtained from a cardiac‐specific, tamoxifen‐activated model of PKP2 deficiency (PKP2cKO). By contrast to PKP2cKO ventricular myocytes, PKP2cKO atrial cardiomyocytes presented no significant differences in intracellular calcium (Ca2+i) transient dynamics, sarcoplasmic reticulum load or action potential morphology. PKP2cKO atrial cardiomyocytes showed elevated reactive oxygen species levels, increased frequency and amplitude of Ca2+ sparks, and increased diastolic [Ca2+]i compared to control; the latter two parameters were further increased by isoproterenol exposure and reversed by exposure to ryanodine receptor blocker dantrolene. We speculate that these isoproterenol‐dependent effects may impact on the exercise‐related atrial arrhythmia risk in ARVC patients. Despite absence of changes in Ca2+i transient dynamics, PKP2cKO atrial cardiomyocytes showed enhanced sarcomere shortening and impaired sarcomere relaxation. Orthogonal transcriptomic analysis of human(GTEx) and PKP2cKO atrial tissue led to identification of 41 transcripts depending on PKP2 expression. Biochemical follow‐up confirmed reduced abundance of sarcomeric protein myosin binding protein C, potentially playing a role in cellular shortening and relaxation changes observed. Our findings provide novel insights into the role of PKP2 in atrial myocardium with potential implications to therapeutic management of atrial fibrillation in patients with PKP2‐related ARVC. Atrial arrhythmias occur in a large group of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), a cardiac disease mostly caused by pathogenic variants in the desmosomal gene plakophilin‐2 (PKP2). Exercise is considered to be an independent risk factor for arrhythmias consequent to PKP2 deficiency. We show that loss of PKP2 expression affects cellular calcium handling and electrophysiology differently in left atrial vs. ventricular myocardium and causes extensive atrial fibrosis. PKP2‐deficient atrial cardiomyocytes present increased spontaneous sarcoplasmic reticulum calcium release events, further enhanced by isoproterenol exposure and reversible by a ryanodine receptor blocker (dantrolene). In addition, PKP2‐deficient atrial myocytes exhibit impaired relaxation and enhanced sarcomere shortening, most probably related to reduced abundance of myosin binding protein C. We speculate that cellular effects reported upon isoproterenol impact on the exercise‐related atrial arrhythmia risk in ARVC patients. We further propose that therapeutic approaches aimed at mitigating ventricular damage may be effective to treat the atrial disease in ARVC. [ABSTRACT FROM AUTHOR]

Soccer is the most popular sport in the world, with over 265 million active players and approximately 0.05% professional players worldwide. The Fédération Internationale de Football Association (FIFA) has made preparticipation screening recommendations which involve electrocardiography and echocardiography being performed prior to international competition. The aim of preparticipation cardiovascular screening in young athletes is to detect asymptomatic individuals with cardiovascular disease at risk of sudden cardiac death (SCD). The incidence of SCD in young athletes (age≤ 35 years) is 0.6–3.6 in 100,000 persons/year, with most deaths due to cardiovascular causes. Arrhythmogenic right ventricular cardiomyopathy (ARVC) is one of the leading causes of SCD in young athletes. It is a genetic disease characterized by progressive fibrofatty replacement of the myocardium with variable phenotypic expression. Exercise‐induced cardiac remodeling in conjunction with extensive T‐wave inversion raises concern for ARVC. This case report and literature review explores a potential mimic for ARVC, the role of cardiovascular screening in sport, and the use of a multimodality approach for risk stratification and management. [ABSTRACT FROM AUTHOR]

Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/−), and wild type (WT) littermates were chronically exposed to 5α‐dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro‐hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super‐resolution microscopy revealed a decrease in NaV1.5 membrane clustering in Plako+/− atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. Key points: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression).In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages.In mice with reduced plakoglobin expression, chronic administration of 5α‐dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane‐localized NaV1.5 clusters.5α‐Dihydrotestosterone, therefore, represents a stimulus aggravating the pro‐arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function. [ABSTRACT FROM AUTHOR]

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterised by progressive fibrosis predominantly of the right ventricular (RV) myocardium, resulting in life-threatening arrhythmias and heart failure. The diagnosis is challenging due to a wide spectrum of clinical symptoms. The important role of ECG was covered in the current diagnostic criteria. The role of the epsilon wave (EW) is still under discussion. Aim: The aim of the study was to examine a potential association between the EW and late ventricular potentials (LPs) in ARVC patients (pts). The correlation between RV dilatation or dysfunction and LPs/EW was also analysed. Methods: The ARVC group consisted of 81 pts (53 men, aged 20–78 years) fulfilling 2010 International Task Force Criteria. 12-lead ECG, LPs, Holter, and ECHO were performed in all pts. The presence of EW was analysed in ECG by 3 investigators. LPs were detected by signal-averaged ECG (SAECG). SAECG was considered positive for LPs when at least two of the three following criteria were met: (1) the filtered QRS duration (fQRS) ≥ 114 msec; (2) the duration of the final QRS fragment in which low-amplitude signals lower than 40 μV are recorded (LAS-40 > 38 msec); and (3) the root mean square amplitude of the last 40 milliseconds of the fQRS complex (RMS-40 < 20 μV). The results were compared with a reference group consisting of 53 patients with RV damage in the course of atrial septum defect (ASD) or Ebstein's Anomaly (EA). Results: In the ARVC group, a significant relationship was observed between the occurrence of EW and the presence of LPs. EW was more common in the LP+ than in the LP- patients (48.1% vs. 6.9%, p < 0001; OR 12.5; 95% CI [2.691–58.063]). In ARVC pts, RVOT > 36 mm, RVIT > 41 mm, and RV S' < 9 cm/s were observed significantly more often in the LPs+ than in the LPs− group (OR [95% CI]: 8.3 [2.9–1.5], 6.4 [2.2–19.0] and 3.6 [1.1–12.2], respectively). In the ARVC group, any of fQRS > 114 ms, LAS > 38 ms, and RMS < 20 μV were significantly more frequent in EW+ pts. In multivariate analysis, the independent factors of the EW were LAS-40 and RV S'. In the LPs− subgroup, RVOT > 36 mm was more frequent in ASD/EA than in ARVC (70.4% vs. 25%, p = 0.002). Similarly, in the LPs− subgroup, RVIT > 41 mm was encountered more frequently in ASD/EA than in ARVC (85.2% vs. 48.3%, p = 0.004). Conclusions: In ARVC, there is an association between EW and LPs, with both probably resulting from the same process of fibrofatty substitution of the RV myocardium. Although RV dilatation is common in ASD and EA, it does not correlate with LPs. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare myocardial genetic disease that leads to heart failure and sudden cardiac death. The diagnosis of ARVC remains challenging given its variable presentation. A 66-year-old woman was admitted to our cardiac intensive care unit for the management of a left heart failure flare-up with an atrial flutter, which remains an atypical mode of the revelation of arrhythmogenic right ventricular cardiomyopathy (ARVC) retained based the association of genetic predisposition, the presence of repolarization abnormalities on electrocardiogram (EKG), the occurrence of an episode of sustained ventricular tachycardia and imaging data. ARVC is a condition with varying expressions, severity, and progression. Early detection, careful monitoring, and appropriate management are crucial in improving outcomes for individuals with ARVC.

Introduction: The 2023 European Society of Cardiology Guidelines for the management of Cardiomyopathies recommends a phenotype-based, multimodal, multidisciplinary, and multiparametric approach to the diagnosis of cardiomyopathies. Case report: We present the case of a 70-year-old man, who underwent a routine preoperative examination before dermatological surgery. Initially, on the electrocardiogram (ECG), non-sustained ventricular tachycardia (nsVT) was seen, whereas a dilated right ventricle was observed on transthoracic echocardiography (TTE). After further cardiological examination, ECG criteria for right ventricular arrhythmogenic cardiomyopathy (ARVC) were fulfilled (negative T waves in V1-V3, presence of an epsilon wave), in addition to significant bradycardia with sinus node dysfunction, and recurrent nsVTs were detected during monitoring. Cardiac magnetic resonance (CMR) scan was performed to assess right ventricular function and morphology, which confirmed a dilated right ventricle (end-diastolic volume normalized to body surface area 155 mL/m2), however, no wall motion abnormality was detected. Transesophageal echocardiography ruled out atrial septal defects as a potential cause for right ventricular dilatation. Overall, a diagnosis of ARVC was established based on the 3 major criteria fulfilled by the 2010 ARVC Task Force Criteria. Subsequently, in view of the sinus node dysfunction and ARVC diagnosis with high risk features, we opted for primary preventive DDD-ICD implantation, followed by long-term drug therapy with beta-blocker therapy. Conclusion: ARVC is a rare structural myocardial disease, which is often challenging to diagnose, and the search for clinical clues and "red flags" (functional and morphological abnormalities, electrophysiological features) is of strategic importance.

Aims Arrhythmogenic right ventricular cardiomyopathy (ARVC) is characterized by progressive myocardial dysfunction and associated with an increased risk of major cardiovascular (CV) events. To determine right heart strain (ventricular and atrial global longitudinal strain (RVGLS and RAGLS) in patients with definite ARVC and its association with adverse events during follow-up. Methods and results RVGLS and RAGLS were analysed in focused right heart apical views from 70 patients using TomTec ImageArena and association with a composite endpoint was determined (sustained ventricular arrhythmia and cardiovascular death). Over a median follow-up duration of 4.9 years, 26 (37%) patients met the endpoint. RVGLS was significantly impaired in the event group (−11.5 [−13.3 to −10.2] %) vs. the no-event group (−15.8 [−17.1 to −14.5] %, P < 0.001), and so was RAGLS (22.8 [21.4–27.4] % vs. 31.5 [25.1–39.6] %, respectively, P < 0.001). In Cox regression, RVGLS (HR 1.36, P < 0.001) and RAGLS (HR 0.92, P = 0.002) were associated with a higher risk of adverse events. In multivariable Cox regression models, RVGLS and RAGLS remained independent of and were incremental to age, gender, and conventional RV parameters, and model fitness was improved when RVGLS and RAGLS were applied together rather than alone. Conclusion RVGLS and RAGLS are more impaired in patients with adverse events and associated with adverse events independent of age, gender, and conventional RV parameters. When RVGLS and RAGLS are applied together, prediction models are improved suggesting that right heart strain may form part of the echocardiographic routine protocol in patients with ARVC. [ABSTRACT FROM AUTHOR]

Right dominant arrhythmogenic cardiomyopathy, commonly known as Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), represents a formidable challenge in cardiovascular medicine, as conventional therapies are commonly ineffective in impeding disease progression and the development of end-stage heart failure. Recombinant adeno-associated virus (AAV)-mediated gene therapy presents a promising avenue for targeted therapeutic interventions, potentially revolutionising treatment approaches for ARVC patients. Encouraging results from preclinical studies have sparked optimism about the possibility of curing specific subtypes of ARVC in the near future. This narrative review delves into the dynamic landscape of genetic therapy for ARVC, elucidating its underlying mechanisms and developmental stages, and providing updates on forthcoming trials. Additionally, it examines the hurdles and complexities impeding the successful translation of ARVC genetic therapies into clinical practice. Despite notable scientific advancements, the journey towards implementing genetic therapies for ARVC patients in real-world clinical settings is still in its early phases. [ABSTRACT FROM AUTHOR]

An 18-year-old male presented with syncope during a training break. Post-syncope, he developed effort dyspnea, which he associated with the Pfizer-BioNTech COVID-19 vaccine received a week earlier. Electrocardiogram showed T inversion in V1-V3, III, and aVF, while 24-hour Holter monitoring revealed frequent ventricular premature beats. A transthoracic echocardiogram showed severe biventricular dilation and mild left ventricular (LV) dysfunction. Cardiac magnetic resonance (CMR) imaging confirmed these findings, showing moderate right ventricular (RV) systolic dysfunction with akinesia of the inferior and inferolateral walls. T2 hypersignal in the middle segment of the inferior inferior interventricular septum suggested myocardial edema. Extensive transmural late gadolinium enhancement was noted in the RV and LV walls. An implantable loop recorder was implanted. Three months later, the patient was admitted with palpitations, fever, and a positive SARS-CoV-2 test. Sustained ventricular tachycardia (VT) episodes were documented and managed with amiodarone and β-blockers. Follow-up CMR showed a slight improvement in LV ejection fraction and resolution of edema. A single-chamber implantable cardioverter-defibrillator (ICD) was implanted. Genetic testing for arrhythmogenic RV cardiomyopathy (ARVC) was negative, and family screening was normal. Two years later, pre-syncope episodes occurred, and ICD interrogation revealed nonsustained VT. The patient is awaiting VT ablation. This case highlights the diagnostic and therapeutic challenges of ARVC, particularly in differentiating it from myocarditis. The "hot-phase" presentation, vaccine association, and subsequent SARS-CoV-2 infection added complexity. CMR was crucial for diagnosis, and VT management required a combination of medical therapy and invasive procedures.

Abstract Introduction Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC. Case presentation A 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement. Conclusion Prompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient.

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC. Case presentation: A 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement. Conclusion: Prompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular myocardium, leading to myocardial atrophy. Although the structural changes usually affect the right ventricle, the pathology may also manifest with either isolated left ventricular myocardium or biventricular involvement. As ARVC shows an autosomal dominant pattern of inheritance with variable penetrance, the clinical presentation of the disease is highly heterogeneous, with different degrees of severity and patterns of myocardial involvement even in patients of the same familiar group with the same gene mutation: the pathology spectrum ranges from the absence of symptoms to sudden cardiac death (SCD) sustained by ventricular arrhythmias, which may, in some cases, be the first manifestation of an otherwise silent pathology. An evidence-based systematic review of the literature was conducted to evaluate the state of the art of the diagnostic techniques for the correct post-mortem identification of ARVC. The research was performed using the electronic databases PubMed and Scopus. A methodological approach to reach a correct post-mortem diagnosis of ARVC was described, analyzing the main post-mortem peculiar macroscopic, microscopic and radiological alterations. In addition, the importance of performing post-mortem genetic tests has been underlined, which may lead to the correct identification and characterization of the disease, especially in those ARVC forms where anatomopathological investigation does not show evident morphostructural damage. Furthermore, the usefulness of genetic testing is not exclusively limited to the correct diagnosis of the pathology, but is essential for promoting targeted screening programs to the deceased's family members. Nowadays, the post-mortem diagnosis of ARVC performed by forensic pathologist remains very challenging: therefore, the identification of a clear methodological approach may lead to both a reduction in under-diagnoses and to the improvement of knowledge on the disease. [ABSTRACT FROM AUTHOR]

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disease characterised by progressive fibrofatty tissue replacement of the myocardium. Several arrhythmogenic cardiomyopathy (ACM) phenotypes are now recognised, including right‐dominant, biventricular, and left‐dominant variants, which led to the development of the 2020 International criteria (Padua criteria). Raising awareness of these variants is crucial as their clinical entity can be concealed. This is particularly important in the athletic population. Exercise can promote the development of the phenotype and accelerate disease progression, resulting in left ventricular (LV) involvement and systolic dysfunction, which can cause ventricular arrhythmias and sudden death. Case Description: A late adolescent male was escorted by paramedics to an emergency department following a medium‐speed motor vehicle accident. A multimodality approach was implemented involving a 12‐lead electrocardiogram (ECG), transthoracic echocardiography (ECHO) and cardiac magnetic resonance (CMR) imaging. An unknown cardiomyopathy was revealed with diagnostic clues suggesting biventricular ACM in a recreational soccer player, when using the Padua criteria. Conclusion: ACM should be considered in the evaluation of an unexplained cardiomyopathy presenting with possible syncopal events. This case describes the clinical features of an ACM patient, emphasising the utility of ECG, ECHO and CMR in determining biventricular involvement. CMR is a powerful tool for the diagnosis of ACM and the identification of myocardial fibrosis with late gadolinium enhancement (LGE). The use of 12‐lead ECG and 2‐dimensional (2D) strain imaging may also raise suspicion of biventricular phenotypes and predict LV involvement with significant myocardial fibrosis. [ABSTRACT FROM AUTHOR]

Aims Catheter ablation of ventricular tachycardia (VT) improves VT-free survival in 'classic' arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to investigate electrophysiological features and ablation outcomes in patients with ARVC and biventricular (BiV) involvement. Methods and results We assembled a retrospective cohort of definite ARVC cases with sustained VTs. Patients were divided into the BiV (BiV involvement) group and the right ventricular (RV) (isolated RV involvement) group based on the left ventricular systolic function detected by cardiac magnetic resonance. All patients underwent electrophysiological mapping and VT ablation. Acute complete success was non-inducibility of any sustained VT, and the primary endpoint was VT recurrence. Ninety-eight patients (36 ± 14 years; 87% male) were enrolled, including 50 in the BiV group and 48 in the RV group. Biventricular involvement was associated with faster clinical VTs, a higher VT inducibility, and more extensive arrhythmogenic substrates (all P < 0.05). Left-sided VTs were observed in 20% of the BiV group cases and correlated with significantly reduced left ventricular systolic function. Catheter ablation achieved similar acute efficacy between these two groups, whereas the presence of left-sided VTs increased acute ablation failure (40 vs. 5%, P = 0.012). Over 51 ± 34 months [median, 48 (22–83) months] of follow-up, cumulative VT-free survival was 52% in the BiV group and 58% in the RV group (P = 0.353). A multivariate analysis showed that younger age, lower RV ejection fraction (RVEF), and non-acute complete ablation success were associated with VT recurrence in the BiV group. Conclusion Biventricular involvement implied a worse arrhythmic phenotype and increased the risk of left-sided VTs, while catheter ablation maintained its efficacy for VT control in this population. Younger age, lower RVEF, and non-acute complete success predicted VT recurrence after ablation. [ABSTRACT FROM AUTHOR]

Background Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long‐term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias. Methods and Results Three hundred fifty‐three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12‐lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10 years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1–14] years. Reductions of QRS voltage, R‐ and T‐wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102 ms (P

Sudden cardiac death (SCD) in athletes, though rare, is the leading cause of exercise-related mortality and poses significant concern due to the symbolic health and vitality of athletes. This review examines the epidemiology, causes, and prevention strategies of SCD in athletes. SCD, defined as sudden death presumed to be of cardiac origin within one hour of symptom onset, affects athletes variably depending on age, race, and type of sports. Key causes include hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC) in younger athletes, and coronary artery disease (CAD) in older athletes. Ion channelopathies and structural heart diseases also contribute significantly. Preparticipation screening (PPE) involving ECGs, lifestyle adjustments, and medical interventions are critical in prevention. Continuous research and adaptive guidelines are essential for safeguarding athletes against these fatal events. Keywords: sudden cardiac death, athletes, sports, exercise, cardiovascular diseases, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, coronary artery disease, ion channelopathies, long QT syndrome, Brugada syndrome, preparticipation screening, electrocardiogram (ECG), risk factors, prevention strategies.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary heart muscle disorder characterized by the progressive replacement of right ventricular myocardium with fibrofatty tissue. This condition predisposes individuals to arrhythmias and an elevated risk of sudden cardiac death (SCD). The etiology of ARVC is predominantly genetic, with mutations in genes encoding desmosomal proteins playing a crucial role. Physical exercise has a significant impact on the progression of ARVC, often exacerbating the disease's severity and increasing the likelihood of life-threatening arrhythmic events. Diagnosing ARVC remains challenging due to its variable clinical presentation and overlapping features with other cardiomyopathies. Advanced imaging techniques, electrocardiography, and genetic testing are essential tools in the diagnostic process. Treatment strategies for ARVC include lifestyle modifications, pharmacotherapy, implantable cardioverter-defibrillators (ICDs), and in some cases, catheter ablation or heart transplantation. Preventing disease progression and SCD involves a multidisciplinary approach, emphasizing early diagnosis, risk stratification, and tailored therapeutic interventions. This review comprehensively examines the etiology of ARVC, the detrimental effects of physical exercise on the disease, the associated SCD risk, and the challenges in diagnosis, while also discussing current treatment modalities and preventive measures to mitigate disease progression. Materials and Methods Review and summary of research studies available in databases on Google Scholar and PubMed. Databases such as PubMed and Google Scholar were searched using the keywords: ‘Arrhythmogenic right ventricular cardiomyopathy, ‘ARVC in athletes’, ‘Sudden cardiac death’, ‘impact of physical exercise on ARVC’.

Catheter ablation of septal ventricular tachycardia (VT) is challenging. Pulsed field ablation is a promising technology, potentially reaching deep substrates. We report the first sequential unipolar biventricular pulsed field ablation targeting refractory septal VT. Besides, we illustrate the importance of searching underlying cardiomyopathy in patients with recurrent multiple morphology VTs and normal magnetic resonance imaging.

Isolated apical ventricular hypoplasia is an extremely rare congenital heart disease. We describe 2 cases, each affecting a different side, presenting with unique clinical and imaging characteristics not hitherto delineated in the literature.

Abstract Objectives Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC. Methods RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan–Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint. Results After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan–Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p

Abstract Background Dilation may be the first right ventricular change and accelerates the progression of threatening ventricular tachyarrhythmias and heart failure for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but the treatment for right ventricular dilation remains limited. Methods Single-cell RNA sequencing (scRNA-seq) of blood and biventricular myocardium from 8 study participants was performed, including 6 end-stage heart failure patients with ARVC and 2 normal controls. ScRNA-seq data was then deeply analyzed, including cluster annotation, cellular proportion calculation, and characterization of cellular developmental trajectories and interactions. An integrative analysis of our single-cell data and published genome-wide association study-based data provided insights into the cell-specific contributions to the cardiac arrhythmia phenotype of ARVC. Desmoglein 2 (Dsg2)mut/mut mice were used as the ARVC model to verify the therapeutic effects of pharmacological intervention on identified cellular cluster. Results Right ventricle of ARVC was enriched of CCL3 + proinflammatory macrophages and TNMD + fibroblasts. Fibroblasts were preferentially affected in ARVC and perturbations associated with ARVC overlap with those reside in genetic variants associated with cardiac arrhythmia. Proinflammatory macrophages strongly interact with fibroblast. Pharmacological inhibition of Nod-like receptor protein 3 (NLRP3), a transcriptional factor predominantly expressed by the CCL3 + proinflammatory macrophages and several other myeloid subclusters, could significantly alleviate right ventricular dilation and dysfunction in Dsg2mut/mut mice (an ARVC mouse model). Conclusions This study provided a comprehensive analysis of the lineage-specific changes in the blood and myocardium from ARVC patients at a single-cell resolution. Pharmacological inhibition of NLRP3 could prevent right ventricular dilation and dysfunction of mice with ARVC.

Objectives: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by progressive fibrofatty infiltration of atrial and ventricular myocardium resulting in adverse cardiac events. Atrial function has been increasingly recognized as prognostically important for cardiovascular disease. As the right atrial (RA) strain is a sensitive parameter to describe RA function, we aimed to analyze the prognostic value of the RA strain in ARVC. Methods: RA strain parameters were derived from cardiac magnetic resonance (CMR) images of 105 participants with definite ARVC. The endpoint was defined as a combination of sudden cardiac death, survival cardiac arrest, and appropriate implantable cardioverter-defibrillator intervention. Cox regression and Kaplan–Meier survival analyses were performed to evaluate the association between RA strain parameters and endpoint. Concordance index (C index), net reclassification index (NRI), and integrated discrimination improvement (IDI) were calculated to assess the incremental value of RA strain in predicting the endpoint. Results: After a median follow-up of 5 years, 36 (34.3%) reaching the endpoint displayed significantly reduced RA strain parameters. At Kaplan–Meier analysis, impaired RA reservoir (RARS) and booster strains (RABS) were associated with an increased risk of the endpoint. After adjusting for conventional risk factors, RARS (hazard ratio [HR], 0.956; p = 0.005) and RABS (HR, 0.906; p = 0.002) resulted as independent predictors for endpoint at Cox regression analyses. In addition, RARS and RABS improved prognostic value to clinical risk factors and CMR morphological and functional predictors (all p < 0.05). Conclusion: RARS and RABS were independent predictors for adverse cardiac events, which could provide incremental prognostic value for conventional predictors in ARVC. Critical relevance statement: We evaluated the prognostic value of right atrial strain in ARVC patients and suggested cardiologists consider RA strain as a predictive parameter when evaluating the long-term outcome of ARVC patients in order to formulate better clinical therapy. Key points: • Patients with ARVC had significantly reduced RA strain and strain rates compared with healthy participants. • Participants with lower RA reservoir and booster stains were associated with a significantly higher risk of adverse cardiac events. • RA booster and reservoir strain provide incremental value to conventional parameters. [ABSTRACT FROM AUTHOR]

Background and Aims Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. Methods This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%–25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. Results One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. Conclusions North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs. [ABSTRACT FROM AUTHOR]

The subcutaneous implantable cardioverter defibrillator (S‐ICD) is often used in young patients such as arrhythmogenic right ventricular cardiomyopathy (ARVC) and Brugada syndrome due to long‐term lead durability issues. Although S‐ICD lead dislodgement is rare, we encountered such an incident in a young ARVC patient during the chronic phase following the two‐incision technique. Remote monitoring system is useful for early diagnosis of electrode movement (Graphical abstract image). When S‐ICD lead dislodgement occurs in active young patients, lead revision using the three‐incision technique may be an option. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disease characterised by early arrhythmias and structural changes. Still, there are limited echocardiography data on its structural progression. We studied structural progression and its impact on the occurrence of major adverse cardiovascular events (MACE). In this single-centre observational cohort study, structural progression was defined as the development of new major or minor imaging 2010 Task Force Criteria during follow-up. Of 101 patients, a definite diagnosis of ARVC was made in 51 patients, while non-definite 'early' disease was diagnosed in 50 patients. During 4 years of follow-up (IQR: 2–6), 23 (45%) patients with a definite diagnosis developed structural progression while only 1 patient in the non-definite (early) group gained minor imaging Task Force Criteria. Male gender was strongly associated with structural progression (62% of males progressed structurally, while 88% of females remained stable). Patients with structural progression were at higher risk of MACE (64% of patients with MACE had structural progression). Therefore, the rate of structural progression is an essential factor to be considered in ARVC studies. [ABSTRACT FROM AUTHOR]

Introduction: The echocardiographic diagnosis criteria for arrhythmogenic right ventricular cardiomyopathy (ARVC) are highly specific but sensitivity is low, especially in the early stages of the disease. The role of echocardiographic strain in ARVC has not been fully elucidated, although prior studies suggest that it can improve the detection of subtle functional abnormalities. The purposes of the study were to determine whether these advanced measures of right ventricular (RV) dysfunction on echocardiogram, including RV strain, increase diagnostic value for ARVC disease detection and to evaluate the association of echocardiographic parameters with arrhythmic outcomes. Methods: The study included 28 patients from the Heart Institute of São Paulo ARVC cohort with a definite diagnosis of ARVC established according to the 2010 Task Force Criteria. All patients were submitted to ECHO's advanced techniques including RV strain, and the parameters were compared to prior conventional visual ECHO and CMR. Results: In total, 28 patients were enrolled in order to perform ECHO's advanced techniques. A total of 2/28 (7%) patients died due to a cardiovascular cause, 2/28 (7%) underwent heart transplantation, and 14/28 (50%) patients developed sustained ventricular arrhythmic events. Among ECHO's parameters, RV dilatation, measured by RVDd (p = 0.018) and RVOT PSAX (p = 0.044), was significantly associated with arrhythmic outcomes. RV free wall longitudinal strain < 14.35% in absolute value was associated with arrhythmic outcomes (p = 0.033). Conclusion: Our data suggest that ECHO's advanced techniques improve ARVC detection and that abnormal RV strain can be associated with arrhythmic risk stratification. Further studies are necessary to better demonstrate these findings and contribute to risk stratification in ARVC, in addition to other well-known risk markers. [ABSTRACT FROM AUTHOR]

Background: Dilation may be the first right ventricular change and accelerates the progression of threatening ventricular tachyarrhythmias and heart failure for patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), but the treatment for right ventricular dilation remains limited. Methods: Single-cell RNA sequencing (scRNA-seq) of blood and biventricular myocardium from 8 study participants was performed, including 6 end-stage heart failure patients with ARVC and 2 normal controls. ScRNA-seq data was then deeply analyzed, including cluster annotation, cellular proportion calculation, and characterization of cellular developmental trajectories and interactions. An integrative analysis of our single-cell data and published genome-wide association study-based data provided insights into the cell-specific contributions to the cardiac arrhythmia phenotype of ARVC. Desmoglein 2 (Dsg2)mut/mut mice were used as the ARVC model to verify the therapeutic effects of pharmacological intervention on identified cellular cluster. Results: Right ventricle of ARVC was enriched of CCL3+ proinflammatory macrophages and TNMD+ fibroblasts. Fibroblasts were preferentially affected in ARVC and perturbations associated with ARVC overlap with those reside in genetic variants associated with cardiac arrhythmia. Proinflammatory macrophages strongly interact with fibroblast. Pharmacological inhibition of Nod-like receptor protein 3 (NLRP3), a transcriptional factor predominantly expressed by the CCL3+ proinflammatory macrophages and several other myeloid subclusters, could significantly alleviate right ventricular dilation and dysfunction in Dsg2mut/mut mice (an ARVC mouse model). Conclusions: This study provided a comprehensive analysis of the lineage-specific changes in the blood and myocardium from ARVC patients at a single-cell resolution. Pharmacological inhibition of NLRP3 could prevent right ventricular dilation and dysfunction of mice with ARVC. [ABSTRACT FROM AUTHOR]

Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15% and 0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age‐ and sex‐matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better‐informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in‐depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non‐dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarizes established and emerging risk factors for life‐threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence‐based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification. [ABSTRACT FROM AUTHOR]

The diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) is challenging because of nonspecific clinical findings and lack of conclusive answers from genetic testing (ie, an ARVC-related variant is neither necessary nor sufficient for diagnosis). Despite the revised 2010 Task Force Criteria, patients are still misdiagnosed with ARVC. In patients referred for ARVC, we sought to identify the clinical characteristics and diagnostic confounders for those patients in whom ARVC was ultimately ruled out. Patients who were referred to our center with previously diagnosed or suspected ARVC (between January 2011 and September 2019; N = 726) were included in this analysis. Among 726 patients, ARVC was ruled out in 365 (50.3%). The most common presenting symptoms in ruled-out patients were palpitations (n = 139, 38.1%), ventricular arrhythmias (n = 62, 17.0%), and chest pain (n = 53, 14.5%). On the basis of outside evaluation, 23.8% of these patients had received implantable cardioverter-defibrillators (ICDs) and device extraction was recommended in 9.0% after reevaluation. An additional 5.5% had received ICD recommendations, all of which were reversed on reevaluation. The most frequent final diagnoses were idiopathic premature ventricular contractions/ventricular tachycardia/ventricular fibrillation (46.6%), absence of disease (19.2%), and noncardiac presyncope/syncope (17.5%). The most common contributor to diagnostic error was cardiac magnetic resonance imaging, including mistaken right ventricular wall motion abnormalities (33.2%) and nonspecific fat (12.1%). False suspicion or misdiagnosis was found in the majority of patients referred for ARVC, resulting in inappropriate ICD implantation or recommendation in 14.5% of these patients. Misdiagnosis or false suspicion was most commonly due to misinterpretation of cardiac magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Improved disease recognition through family screening and increased life expectancy with appropriate sudden cardiac death prevention has increased the burden of heart failure in arrhythmogenic cardiomyopathy (ACM). Heart failure management guidelines are well established but primarily focus on left ventricle function. A significant proportion of patients with ACM have predominant or isolated right ventricle (RV) dysfunction. Management of RV dysfunction in ACM lacks evidence but requires special considerations across the spectrum of heart failure regarding the initial diagnosis, subsequent management, monitoring for progression, and end-stage disease management. In this review, we discuss the unique aspects of heart failure management in ACM with a special focus on RV dysfunction. [ABSTRACT FROM AUTHOR]

This document provides an overview of the 2023 ESC guidelines for the management of cardiomyopathies. The guidelines aim to assist healthcare professionals in diagnosing and managing patients with cardiomyopathies based on the best available clinical evidence. They propose a classification system with five phenotypes of cardiomyopathies and emphasize the importance of a multidisciplinary approach to patient care. The guidelines recommend the use of contrast-enhanced cardiac magnetic resonance and genetic testing for diagnostic purposes. Treatment options include medication, devices, and cardiac transplantation, and exercise recommendations are tailored to individual patients. [Extracted from the article]

Abstract Aims In this study, we aimed to develop and validate a competing risk nomogram for predicting cardiac death and heart transplantation (HT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods We retrospectively enrolled 149 consecutive patients with ARVC diagnosed at our institution between 2008 and 2022. Cox proportional hazards model was primarily used to identify variables associated with cardiac death and HT. On the basis of these indicators, a competing risk nomogram was developed to predict the 1, 3, and 5 year probabilities of cardiac death and HT. The area under the receiver operating characteristic curve (AUC), Harrell's C‐index, and calibration curves were used to evaluate and internally validate the performance of the model. Decision curve analysis was performed to assess the clinical utility of the nomogram. Result Of the 149 patients with ARVC, the mean age was 38.77 ± 15.94 years, and most of the patients were men (67.11%, 100/149). Fourteen patients experienced cardiac death and nine underwent HT, during a median follow‐up period of 5.8 years (interquartile range, 0.62–5.56 years). Multivariable COX analysis revealed that extent of TWI in the anterior and inferior leads (P = 0.0057), right atrial diameter on transthoracic echocardiography (P = 0.0498), RVEF (P = 0.1036), and LVEF (P < 0.001) all showed statistical significance. The 1‐, 3‐, and 5‐year cumulative incidence of cardiac death and HT were 3.35%, 8.05%, and 11.4%, respectively. The area under the receiver operating characteristic curve of the nomogram for predicting cardiac death and HT at 1, 3, and 5 years after diagnosis of ARVC were 0.860, 0.935, and 0.956. The value of Harrell's C‐index is 0.9273 (95% confidence interval 0.8954–0.9590; P

A 76-year-old male patient presented to the emergency room with acute decompensated right heart failure and presyncope episodes. Upon admission, his electrocardiogram (ECG) showed sustained monomorphic ventricular tachycardia at 180 bpm, which was electrically cardioverted, and the patient was subsequently admitted to the intensive care unit. The echocardiography showed a very dilated right ventricle (RV) with global systolic dysfunction and akinetic anterior and lateral walls. The coronary angiography was normal. The cardiac magnetic resonance showed signs of fibro-fatty replacement of the RV myocardium. Furthermore, the ECG after cardioversion showed inverted T waves and an epsilon wave in V1–V3 leads and late potentials by signal-averaged ECG. As such, a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC) was suspected. However, he presented no familial history of ARVC, was 76 years of age at the time of diagnosis and was asymptomatic until now. Given these considerations, we performed a right ventricular angiography which showed dilatation of the RV with akinetic/dyskinetic bulging, creating the “pile d’assiettes” image suggestive of ARVC. In the case of this patient, the RV angiography contributed to establish a diagnosis of ARVC with a very late presentation, to our knowledge the latest presentation in terms of age described in the literature.

Right dominant arrhythmogenic cardiomyopathy, commonly known as Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), represents a formidable challenge in cardiovascular medicine, as conventional therapies are commonly ineffective in impeding disease progression and the development of end-stage heart failure. Recombinant adeno-associated virus (AAV)-mediated gene therapy presents a promising avenue for targeted therapeutic interventions, potentially revolutionising treatment approaches for ARVC patients. Encouraging results from preclinical studies have sparked optimism about the possibility of curing specific subtypes of ARVC in the near future. This narrative review delves into the dynamic landscape of genetic therapy for ARVC, elucidating its underlying mechanisms and developmental stages, and providing updates on forthcoming trials. Additionally, it examines the hurdles and complexities impeding the successful translation of ARVC genetic therapies into clinical practice. Despite notable scientific advancements, the journey towards implementing genetic therapies for ARVC patients in real-world clinical settings is still in its early phases.

Background Strain analysis is a sensitive method for the assessment of ventricular structural or functional alterations. The authors aimed to determine whether right ventricular (RV) strain parameters can discriminate patients with revised Task Force Criteria–diagnosed arrhythmogenic RV cardiomyopathy (ARVC) incremental to the existing cardiovascular magnetic resonance (CMR) criteria, thus improving the diagnostic yield of CMR in ARVC. Methods and Results A total of 74 patients with revised Task Force Criteria–diagnosed ARVC (37 borderline and 37 definite) and 37 controls were retrospectively enrolled for analysis. Using CMR feature tracking, RV global longitudinal (GLS), circumferential, and radial strain of all participants were evaluated. Compared with controls, the study patients demonstrated significantly impaired global biventricular strain in all 3 directions (all P50% presenting with impaired RV GLS. When both conventional criteria and RV GLS were considered together, this new diagnostic method demonstrated an overall diagnostic accuracy of 90%. The likelihood ratio test showed a significant incremental diagnostic value of RV GLS (P=0.02) over the existing CMR major criteria. Conclusions The current study showed an improved diagnostic accuracy when both RV GLS and the existing CMR criteria were considered together, especially for patients with borderline diagnosis, suggesting the incremental value of strain analysis to the initial assessment of ARVC.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable cardiomyopathy characterized by a predominantly arrhythmic presentation. It represents the leading cause of sudden cardiac death (SCD) among athletes and poses a significant morbidity threat in the general population. As a causative treatment for ARVC is still not available, the placement of an implantable cardioverter defibrillator represents the current cornerstone for SCD prevention in this setting. Thanks to international ARVC-dedicated efforts, significant steps have been achieved in recent years towards an individualized, patient-centred risk stratification approach. A novel risk calculator algorithm estimating the 5-year risk of arrhythmias of patients with ARVC has been introduced in clinical practice and subsequently validated. The purpose of this article is to summarize the body of evidence that has allowed the development of this tool and to discuss the best way to implement its use in the care of an individual patient. [ABSTRACT FROM AUTHOR]

Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare inherited disorder usually affecting the right ventricle (RV), characterized by fibro‐fatty tissue replacement of the healthy ventricular myocardium. It often predisposes young patients to ventricular tachycardia, heart failure, and/or sudden cardiac death. However, recent studies have suggested predominantly left ventricle (LV) involvement with variable and/or atypical manifestations. Cardiac magnetic resonance (CMR) imaging has emerged as the noninvasive gold standard for the diagnosis of ARVC. Case Summary: A 21‐year‐old athletic male with a family history of unknown ventricular arrhythmias, presented with near syncope, chest pain, and exertional palpitations. He had an initial work‐up that was grossly unremarkable including an electrocardiogram (ECG), echocardiogram and a CMR study. Six months later, he presented again with recurrent symptoms of presyncope during exercise and his ECG demonstrated new findings of a terminal activation delay in his precordial leads. He had markedly elevated cardiac biomarkers, (troponin I > 100 ng/dl, normal value < 0.04 ng/dl) and demonstrated ventricular tachycardia with a right bundle branch morphology. An endomyocardial biopsy did not reveal any pathology. A follow‐up CMR demonstrated the new development and prominent left ventricular epicardial scar in the lateral wall. The patient underwent familial genetic testing, which confirmed the presence of an isolated junction plakoglobin (JUP) gene mutation and showed multiple genes consistent with ARVC in his mother. Thus, he manifested a partial transmission of only one abnormal gene for ARVC and exhibited a markedly different expression in his disease without evidence of typical right‐sided heart pathology. A third CMR study was performed, which showed partial improvement in myocardial fibrosis after exercise cessation. Conclusion: We present a case of a young athletic male with a newly diagnosed isolated JUP gene mutation and a genetically diagnosed family history of ARVC. During his course, he demonstrated the progression of new, atypical, left ventricular fibrosis. This case demonstrates a complex interplay between genetic penetrance, phenotypical heterogeneity, and lifestyle factors such as exercise in disease progression and provides insight into the natural course of an isolated JUP mutation. Although rare, clinicians should have a high threshold for the clinical suspicion of ARVC or variants of this disorder even in the absence of classic right‐sided pathologies. [ABSTRACT FROM AUTHOR]

Aim To investigate the effects of coronary artery stenosis on cardiac pathology and myocardial metabolomics in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods Coronary and ventricular sites (anterior, lateral and posterior walls of left ventricle and anterior, posterior wall of right ventricle and interventricular septum) were studied in 35 patients with ARVC undergoing heart transplantation. Coronary artery tissue sections were stained with HE and the degree of stenosis was quantitatively analyzed; slices of ventricular tissue were stained with Masson staining, and the proportion of myocadium, fiber, and adipose tissue in the heart was quantitatively analyzed after image processing. Metabolite extraction and metabolomics analysis of cardiac tissue from coronary artery supply areas were performed. Comparative analysis was conducted on the differences in myocardium, fiber and adipose tissue, and metabolomic profiles among the group of patients without coronary artery stenosis, with mild coronary artery stenosis (<50%) and with moderate-severe coronary artery stenosis (≥50%). Results Among the 35 patients with ARVC, 10 (28. 6%) had moderate-severe coronary artery stenosis, 11 (31. 4%) had mild coronary artery stenosis, and 14 (40. 0%) had no coronary artery stenosis. The age of patients with moderate-severe coronary artery stenosis receiving heart transplantation was significantly higher than those with mild coronary artery stenosis and those without coronary artery stenosis [(48. 5±10. 7) years vs. (33. 8±10. 5) years and (31. 0±13. 4) years, P =0. 015]. There was no statistically significant difference in the proportion of myocardium, fiber and adipose tissue between patients with moderate-severe, mild coronary artery stenosis and those without coronary artery stenosis in the left ventricular anterior wall, lateral wall, posterior wall, and right ventricular anterior wall, posterior wall, and interventricular septum (P>0. 05). There were 105 metabolites were detected from the metabolic profiles, which attributed to pathways of tricarboxylic acid cycle, amino acid metabolism, purine metabolism, pyrimidine metabolism, pentose phosphate metabolism, glycolysis and gluconeogenesis. Metabolomic analysis showed few differences among the three groups. There was no significant separation of the three groups on heat or in principle component analysis. Conclusion There was no difference in the proportion of myocardium, fiber and adipose tissue of the heart and metabolomic profiles among ARVC patients with moderate-severe, mild coronary artery stenosis and without coronary artery stenosis. [ABSTRACT FROM AUTHOR]

The aim is to provide healthcare professionals with a practical diagnostic and treatment framework for patients of all ages and, as an increasing number of patients have a known genetic basis for their disease, the guideline also considers the implications of a diagnosis for families and provides advice on reproduction and contraception. Keywords: Guidelines; Arrhythmia; Arrhythmogenic right ventricular cardiomyopathy; Cardiomyopathies; Diagnosis; Dilated cardiomyopathy; Genetics; Genetic counselling; Genetic testing; Hypertrophic cardiomyopathy; Implantable cardioverter defibrillator; Management; Multimodality imaging; Non-dilated left ventricular cardiomyopathy; Pregnancy; Restrictive cardiomyopathy; Risk stratification; Screening; Sports; Sudden cardiac death EN Guidelines Arrhythmia Arrhythmogenic right ventricular cardiomyopathy Cardiomyopathies Diagnosis Dilated cardiomyopathy Genetics Genetic counselling Genetic testing Hypertrophic cardiomyopathy Implantable cardioverter defibrillator Management Multimodality imaging Non-dilated left ventricular cardiomyopathy Pregnancy Restrictive cardiomyopathy Risk stratification Screening Sports Sudden cardiac death 3503 3626 124 10/04/23 20231001 NES 231001 Table of contents 1. ESC Guidelines do not override the individual responsibility of health professionals to make appropriate and accurate decisions in consideration of each patient's health condition and in consultation with that patient or the patient's caregiver where appropriate and/or necessary. The NDLVC phenotype will include individuals that up until now may have variably been described as having DCM (but without LV dilatation), arrhythmogenic left ventricular cardiomyopathy (ALVC), left-dominant ARVC, or arrhythmogenic DCM (but often without fulfilling diagnostic criteria for ARVC) ( I Figure 3 i ). [Extracted from the article]

Purpose of Review: This article aims to review the accurate classification of non-ischemic cardiomyopathy, including the methods, basis, subtype characteristics, and prognosis, especially the similarities and differences between different classifications. Recent Findings: Non-ischemic cardiomyopathy refers to a myocardial disease that excludes coronary artery disease or ischemic injury and has a variety of etiologies and high incidence. Recent studies suggest that traditional classification methods based on primary/mixed/acquired or genetic/non-genetic cannot meet the precise needs of contemporary clinical management. This article systematically describes the history of classifications of cardiomyopathy and presents etiological and genetic differences between cardiomyopathies. The accurate classification is described from the perspective of morphology, function, and genomics in hypertrophic cardiomyopathy, dilated cardiomyopathy, restrictive cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, left ventricular noncompaction, and partially acquired cardiomyopathy. The different clinical characteristics and treatment needs of these cardiomyopathies are elaborated. Some single-gene mutant cardiomyopathies have unique phenotypes, and some cardiomyopathies have mixed phenotypes. These special classifications require personalized precision treatment, which is worthy of independent research. Summary: This article describes recent advances in the accurate classification of non-ischemic cardiomyopathy from clinical phenotypes and causative genes, discusses the advantages and usage scenarios of each classification, compares the differences in prognosis and patient management needs of different subtypes, and summarizes common methods and new exploration directions for accurate classification. [ABSTRACT FROM AUTHOR]

Aims: In this study, we aimed to develop and validate a competing risk nomogram for predicting cardiac death and heart transplantation (HT) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods: We retrospectively enrolled 149 consecutive patients with ARVC diagnosed at our institution between 2008 and 2022. Cox proportional hazards model was primarily used to identify variables associated with cardiac death and HT. On the basis of these indicators, a competing risk nomogram was developed to predict the 1, 3, and 5 year probabilities of cardiac death and HT. The area under the receiver operating characteristic curve (AUC), Harrell's C‐index, and calibration curves were used to evaluate and internally validate the performance of the model. Decision curve analysis was performed to assess the clinical utility of the nomogram. Result: Of the 149 patients with ARVC, the mean age was 38.77 ± 15.94 years, and most of the patients were men (67.11%, 100/149). Fourteen patients experienced cardiac death and nine underwent HT, during a median follow‐up period of 5.8 years (interquartile range, 0.62–5.56 years). Multivariable COX analysis revealed that extent of TWI in the anterior and inferior leads (P = 0.0057), right atrial diameter on transthoracic echocardiography (P = 0.0498), RVEF (P = 0.1036), and LVEF (P < 0.001) all showed statistical significance. The 1‐, 3‐, and 5‐year cumulative incidence of cardiac death and HT were 3.35%, 8.05%, and 11.4%, respectively. The area under the receiver operating characteristic curve of the nomogram for predicting cardiac death and HT at 1, 3, and 5 years after diagnosis of ARVC were 0.860, 0.935, and 0.956. The value of Harrell's C‐index is 0.9273 (95% confidence interval 0.8954–0.9590; P < 0.001), indicating that the model had good discriminative ability in internal validation. Decision curve analysis revealed that our model was clinically useful within the entire range of potential treatment thresholds in most cases. The cumulative incidence of the primary outcomes was significantly different between the three risk groups according to nomogram‐derived scores (P < 0.001). Conclusions: On the basis of a retrospective review of patients with ARVC at a single centre, we developed a novel nomogram for predicting the risk of cardiac death and HT after ARVC diagnosis. This competing risk nomogram based on four readily available clinical parameters (right atrial diameter, right and left ventricular ejection fraction, and T‐wave inversion) is a potentially useful tool for individualized prognostic assessment in patients with ARVC. [ABSTRACT FROM AUTHOR]

Introduction: The histopathological characteristics of the overlapping disease states of Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been fully elucidated. Methods: A 71‐year‐old man showed coved‐type ST‐segment elevation with the right precordial leads, and the echocardiography demonstrated right ventricular (RV) dilatation. After 11 months, he died of a polymorphic VT storm. Results: The pathological tissue demonstrated fibrofatty degeneration in the free wall of the RV outflow tract based on the heart autopsy. Conclusion: The overlapping disease states of BrS and ARVC showed histopathological characteristics consistent with ARVC. [ABSTRACT FROM AUTHOR]

COVID-19 infection can cause cardiac arrhythmias through both direct and indirect mechanisms. We report a case of a patient who presented with sustained ventricular tachycardia in the context of a COVID-19 infection, leading to a diagnosis of arrhythmogenic right ventricular cardiomyopathy (ARVC). Management of this patient was further influenced by post-acute sequelae of SARS-COV-2 infection. [ABSTRACT FROM AUTHOR]

Arrhythmogenic right ventricular cardiomyopathy (ARVC) can lead to sudden cardiac death and life-threatening heart failure. Due to its high fatality rate and limited therapies, the pathogenesis and diagnosis biomarker of ARVC needs to be explored urgently. This study aimed to explore the lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) network in ARVC. The mRNA and lncRNA expression datasets obtained from the Gene Expression Omnibus (GEO) database were used to analyze differentially expressed mRNA (DEM) and lncRNA (DElnc) between ARVC and non-failing controls. Differentially expressed miRNAs (DEmiRs) were obtained from the previous profiling work. Using starBase to predict targets of DEmiRs and intersecting with DEM and DElnc, a ceRNA network of lncRNA-miRNA-mRNA was constructed. The DEM and DElnc were validated by real-time quantitative PCR in human heart tissue. Protein–protein interaction network and weighted gene co-expression network analyses were used to identify hub genes. A logistic regression model for ARVC diagnostic prediction was established with the hub genes and their ceRNA pairs in the network. A total of 448 DEMs (282 upregulated and 166 downregulated) were identified, mainly enriched in extracellular matrix and fibrosis-related GO terms and KEGG pathways, such as extracellular matrix organization and collagen fibril organization. Four mRNAs and two lncRNAs, including COL1A1, COL5A1, FBN1, BGN, XIST, and LINC00173 identified through the ceRNA network, were validated by real-time quantitative PCR in human heart tissue and used to construct a logistic regression model. Good ARVC diagnostic prediction performance for the model was shown in both the training set and the validation set. The potential lncRNA-miRNA-mRNA regulatory network and logistic regression model established in our study may provide promising diagnostic methods for ARVC.

Electrocardiographic (ECG) findings of T-wave inversions in V1–V3, with or without accompanying epsilon waves, often raise concerns for the rare, but potentially lethal, arrhythmogenic right ventricular cardiomyopathy (ARVC). However, this pattern may be found in pericardial agenesis, an even rarer pathology. Concomitant myocarditis can confuse this presentation further. We report a case of a previously healthy man who presented with left-sided chest pain, ECG findings suggestive of ARVC, and a final diagnosis of myocarditis with underlying partial pericardial agenesis. A growing number of cases have reported pericardial agenesis demonstrating ECG changes similar to ARVC. We discuss an approach to a diagnostically challenging patient. This case emphasizes the importance of a broad differential and the danger of premature closure. [ABSTRACT FROM AUTHOR]