Right ventricular scalloping index as cardiac magnetic resonance-derived marker for diagnosis of arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: The cardiac magnetic resonance (CMR) evaluation of right ventricular (RV) morphologic abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is subjective. Here, we aimed to use a quantitative index, the right ventricular scalloping index (RVSI), to standardize the measurement of RV free wall scalloping and aid in the imaging diagnosis. METHODS: We retrospectively included 15 patients with definite ARVC and 45 age- and sex-matched patients with idiopathic right ventricular outflow tract ventricular arrhythmia (RVOT-VA) as controls. The RVSI was measured from cine images on four-chamber view to evaluate its ability to distinguish between ARVC and RVOT-VA patients. Other cardiac functional parameters including strain analysis were also performed. RESULTS: The RVSI was significantly higher in the ARVC than RVOT-VA group (1.56 ± 0.23 vs 1.30 ± 0.08, p < 0.001). The diagnostic performance of the RVSI was superior to the RV global longitudinal, circumferential, and radial strains, RV ejection fraction, and RV end-diastolic volume index. The RVSI demonstrated high intraobserver and interobserver reliability (intraclass correlation coefficient, 0.94 and 0.96, respectively). RVSI was a strong discriminator between ARVC and RVOT-VA patients (area under curve [AUC], 0.91; 95% CI, 0.82-0.99). A cutoff value of RVSI ≥1.49 provided an accuracy of 90.0%, specificity of 97.8%, sensitivity of 66.7%, positive predictive value (PPV) of 90.9%, and a negative predictive value (NPV) of 89.8%. In a multivariable analysis, a family history of ARVC or sudden cardiac death (odds ratio, 38.71; 95% CI, 1.48-1011.05; p = 0.028) and an RVSI ≥1.49 (odds ratio, 64.72; 95% CI, 4.58-914.63; p = 0.002) remained predictive of definite ARVC. CONCLUSION: RVSI is a quantitative method with good performance for the diagnosis of definite ARVC.

[Diagnosis and treatment of arrhythmogenic cardiomyopathy in children].

Objective: To summarize the clinical manifestations, experiences in diagnosis and treatment of arrhythmogenic cardiomyopathy (ACM) in children. Methods: A retrospective analysis of the clinical manifestations, laboratory tests, radiological features, treatment and follow-up results was conducted in 11 children diagnosed with ACM at the center of congenital heart disease, Beijing anzhen hospital from May 2010 to March 2022. Results: A total of 11 patients aged 2 to 16 years, including 5 males and 6 females were diagnosed with ACM. The clinical manifestations included decreased activity tolerance (7 patients), heart failure (4 patients), syncope or sudden death (3 patients), palpitation (3 patients), and chest tightness and pain (3 patients). Electrocardiogram showed right bundle branch block in 9 cases, paroxysmal ventricular tachycardia in 4 cases, frequent premature ventricular contraction in 4 cases, ventricular pre-excitation in 1 case, left bundle branch block in 1 case, and first degree atrioventricular block in 2 cases. Echocardiography showed enlargement of the right heart, widening of the right ventricular outflow tract, and thinning and bulging of the local wall of the right ventricle with reduced pulsation. Ventricular thrombosis was found in 2 cases. Six children underwent cardiac magnetic resonance imaging, which mainly showed severe enlargement of the right heart, thin free wall of the right ventricle, decreased right heart function, enhanced right ventricular myocardium, and formation of right ventricular aneurysm. Two children underwent myocardial biopsy examination and presented with typical pathological changes of ACM. Genetic tests in five patients revealed DSG2 gene mutation in 2 cases, PKP2 gene mutation in 2 cases, and MYH6 gene mutation in 1 case. All patients received anti heart failure treatment and antiarrhythmic drugs. Two children received anticoagulant treatment due to ventricular thrombosis. Radiofrequency ablation was performed in 2 patients. Glenn procedure was performed in 4 patients, and heart transplantation was performed in 1 patient due to progressive heart failure. The follow-up period ranged from 6 months to 12 years. Two cases died of right heart failure, 6 cases had different degrees of heart failure, 1 case had intermittent chest tightness and pain, and 2 cases were stable. Conclusions: ACM is a progressive genetic cardiomyopathy characterized by decreased activity tolerance, cardiac failure and arrhythmia in pediatric patients. The diagnosis is mainly based on clinical manifestations, electrocardiogram, cardiac imaging changes, and genetic testing. Early detection, diagnosis, and personalized treatment can improve the prognosis.

Catheter ablation of ventricular tachycardia in patients with arrhythmogenic right ventricular cardiomyopathy and biventricular involvement.

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.

Heterozygous desmoplakin (DSP) variants presenting with early onset cardiomyopathy and refractory ventricular tachycardia.

Arrhythmogenic cardiomyopathy is a non-ischaemic cardiomyopathy characterised by the presence of myocardial dysfunction and inherited conduction disease that predisposes patients to malignant ventricular arrhythmias and sudden cardiac death. There is a growing awareness of the diverse phenotypic presentation of arrhythmogenic cardiomyopathy, which may demonstrate preferential involvement of the left, right or both ventricles. A subset of arrhythmogenic cardiomyopathy may be due to mutations of desmosomes, intercellular junctions of the myocardium that promote structural and electrical integrity. Mutations of desmoplakin, encoded by the DSP gene and a critical constituent protein of desmosomes, have been implicated in the onset of arrhythmogenic cardiomyopathy. We present a structured case report of desmoplakin arrhythmogenic cardiomyopathy secondary to novel heterozygous DSP mutations (c.1061T>C and c.795G>C) manifesting as early onset non-ischaemic cardiomyopathy and recurrent ventricular tachycardia refractory to multiple modalities of therapy, including oral antiarrhythmics, cardiac ablation and bilateral sympathectomy, as well as frequent implantable cardioverter-defibrillator discharges.

Detection of gene mutation in the prognosis of a patient with arrhythmogenic right ventricular cardiomyopathy: a case report.

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. CASE PRESENTATION: 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.

The Heart Has its Reasons Which Reason Knows Not: A Curious Case of Chest Pain.

BACKGROUND: 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. CASE REPORT: 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. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: 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.

A missense variant in MYOF is associated with ARVC and sudden cardiac death.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is rare autosomal dominant genetic disorder that leads to severe arrhythmia and sudden cardiac death. Although previous studies in clinical, pathological and genetics of ARVC established consensus diagnostic criteria and expanded the spectrum of pathogenic genes, there is still a proportion of patients with unclear causative factors. Here, whole-exome sequencing was employed to investigate the genetic etiology of a 15-year-old sudden cardiac death female caused by ARVC. A novel variant of MYOF (NM_013451.3: c.4723G > C: p.D1575H) was identified, which is a member of the Ferlin family of proteins is associated with cardiomyopathy. And the bioinformatics analysis predicted the pathogenicity of this variant. We report the first variant of MYOF in ARVC, which imply a vital role of MYOF in cardiomyopathy.

Risk of atrial arrhythmias in patients with ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: In arrhythmogenic right ventricular cardiomyopathy (ARVC), risk of atrial arrhythmias (AAs) persists after ventricular tachycardia (VT) ablation. OBJECTIVE: The purpose of this study was to determine the type, prevalence, outcome, and risk correlates of AA in ARVC in patients undergoing VT ablation. METHODS: Prospectively collected procedural and clinical data on ARVC patients undergoing VT ablation were analyzed. Risk score for typical atrial flutter was determined from univariate logistic regression analysis. RESULTS: Of 119 consecutive patients with ARVC and VT ablation, 40 (34%) had AA: atrial fibrillation (AF) in 31, typical isthmus-dependent atrial flutter (AFL) in 27, and atrial tachycardia/atypical flutter (AT) in 10. Seventeen patients (43%) with AA experienced inappropriate defibrillator therapy, with 15 patients experiencing shocks. Ablation was performed for typical AFL in 21 (53%), AT in 5 (13%), and pulmonary vein isolation for AF in 4 (10%) patients and prevented AA in 78% and all AFL during additional mean follow-up of 65 months. Risk score for typical flutter included age >40 years (1 point), ≥moderate right ventricular dysfunction (2 points), ≥moderate tricuspid regurgitation (2 points), ≥moderate right atrial dilation (2 points), and right ventricular volume >250 cc (3points), with score >4 identifying 50% prevalence of typical flutter. CONCLUSION: AAs are common in patients with ARVC and VT, can result in inappropriate implantable cardioverter-defibrillator shocks, and typically are controlled with atrial ablation. A risk score can be used to identify patients at high risk for typical AFL who may be considered for isthmus ablation at the time of VT ablation.

Management of arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disease characterised by fibrofatty replacement of the ventricular myocardium due to specific mutations, leading to ventricular arrhythmias and sudden cardiac death. Treating this condition can be challenging due to progressive fibrosis, phenotypic variations and small patient cohorts limiting the feasibility of conducting meaningful clinical trials. Although widely used, the evidence base for anti-arrhythmic drugs is limited. Beta-blockers are theoretically sound, yet their efficacy in reducing arrhythmic risk is not robust. Additionally, the impact of sotalol and amiodarone is inconsistent with studies reporting contradictory results. Emerging evidence suggests that combining flecainide and bisoprolol may be efficacious.Radiofrequency ablation has shown some potential in disrupting ventricular tachycardia circuits, with combined endo and epicardial ablation yielding better results which could be considered at the index procedure. In addition, stereotactic radiotherapy may be a future option that can decrease arrhythmias beyond simple scar formation by altering levels of Nav1.5 channels, Connexin 43 and Wnt signalling, potentially modifying myocardial fibrosis.Future therapies, such as adenoviruses and GSk3b modulation, are still in early-stage research. While implantable cardioverter-defibrillator implantation is a key intervention for reducing arrhythmic death, the risks of inappropriate shocks and device complications must be carefully considered.

The pivotal role of compelling high-risk electrocardiographic markers in prediction of ventricular arrhythmic risk in arrhythmogenic right ventricular cardiomyopathy: A systematic review and meta-analysis.

INTRODUCTION: Several investigations have shown that existing risk stratification processes remain insufficient for stratifying sudden cardiac death risk in arrhythmogenic right ventricular cardiomyopathy (ARVC). Multiple auxiliary parameters are investigated to offer a more precise prognostic model. Our aim was to assess the association between several ECG markers (epsilon waves, prolonged terminal activation duration (TAD) of QRS, fragmented QRS (fQRS), late potentials on signal-averaged electrocardiogram (SA-ECG), T-wave inversion (TWI) in right precordial leads, and extension of TWI in inferior leads) with the risk of developing poor outcomes in ARVC. METHODS: A systematic literature search from several databases was conducted until September 9th, 2023. Studies were eligible if it investigated the relationship between the ECG markers with the risk of developing ventricular arrhythmic events. RESULTS: This meta-analysis encompassed 25 studies with a total of 3767 participants. Our study disclosed that epsilon waves, prolonged TAD of QRS, fQRS, late potentials on SA-ECG, TWI in right precordial leads, and extension of TWI in inferior leads were associated with the incremental risk of ventricular arrhythmias, implantable cardioverter-defibrillator shock, and sudden cardiac death, with the risk ratios ranging from 1.46 to 2.11. In addition, diagnostic test accuracy meta-analysis stipulated that the extension of TWI in inferior leads had the uppermost overall area under curve (AUC) value amidst other ECG markers apropos of our outcomes of interest. CONCLUSION: A multivariable risk assessment strategy based on the previously stated ECG markers potentially enhances the current risk stratification models in ARVC patients, especially extension of TWI in inferior leads.

Epidemiology of arrhythmogenic ventricular cardiomyopathy in China.

BACKGROUND: Arrhythmogenic ventricular cardiomyopathy (AVC) is a common cause of ventricular arrhythmias and mortality, but limited data are available from large Asian cohorts. Our aim was to explore the current status of AVC and second, we examined the prevalence of ventricular tachycardia (VT), heart failure (HF) and mortality in patients with AVC in the Chinese population. HYPOTHESIS: At present, some studies have reported that the incidence of AVC is on the rise, which may be due to the increasing number of diagnostic methods for AVC. However, there is no epidemiological data on AVC in the Chinese population, so we speculate that the incidence of AVC in the Chinese population is increasing. METHODS AND RESULTS: We studied 15 888 adults from the Beijing Municipal Health Commission Information Center (BMHCIC) registry database in China from January 2010 to December 2020, and calculated the average annual percentage change (AAPC). Second, we determined the incidence of VT, HF and mortality in patients with AVC. Of the 10 318 men and 5570 women who were screened by cardiac magnetic resonance or examined by myocardial biopsy, there were a total of 256 newly diagnosed AVC patients (mean [SD]: 37.54[17.10]; 39.45% female). The incidence of AVC increased from 7.60 (3.12-12.06) in 2010 to 19.62 (11.51-27.75) per 1000 person-years in 2020. Males had higher incidence of AVC than females. The AAPC for the rising incidence of AVC was 8.9 %. Males had similar VT prevalence (70.32% vs. 62.38%, p = 0.19) and mortality (1.94% vs. 1.98%, p = 0.98) but lower HF prevalence (42.58% vs. 60.40%, p = 0.006), when compared to females. Radiofrequency ablation (RFA) was more likely to be performed in males (p = 0.006). CONCLUSIONS: The rising trend in AVC incidence was evident, with two-fold increase by 2020. Males with AVC had similar VT prevalence and mortality rate, but HF prevalence were lower than females, perhaps impacted by RFA use.

Basic and translational mechanisms in inflammatory arrhythmogenic cardiomyopathy.

Arrhythmogenic cardiomyopathy (ACM) is a familial, nonischemic heart disease typically inherited via an autosomal dominant pattern (Nava et al., [1]; Wlodarska et al., [2]). Often affecting the young and athletes, early diagnosis of ACM can be complicated as incomplete penetrance with variable expressivity are common characteristics (Wlodarska et al., [2]; Corrado et al., [3]). That said, of the five desmosomal genes implicated in ACM, pathogenic variants in desmocollin-2 (DSC2) and desmoglein-2 (DSG2) have been discovered in both an autosomal-recessive and autosomal-dominant pattern (Wong et al., [4]; Qadri et al., [5]; Chen et al., [6]). Originally known as arrhythmogenic right ventricular dysplasia (ARVD), due to its RV prevalence and manifesting in the young, the disease was first described in 1736 by Giovanni Maria Lancisi in his book "De Motu Cordis et Aneurysmatibus" (Lancisi [7]). However, the first comprehensive clinical description and recognition of this dreadful disease was by Guy Fontaine and Frank Marcus in 1982 (Marcus et al., [8]). These two esteemed pathologists evaluated twenty-two (n = 22/24) young adult patients with recurrent ventricular tachycardia (VT) and RV dysplasia (Marcus et al., [8]). Initially, ARVD was thought to be the result of partial or complete congenital absence of ventricular myocardium during embryonic development (Nava et al., [9]). However, further research into the clinical and pathological manifestations revealed acquired progressive fibrofatty replacement of the myocardium (McKenna et al., [10]); and, in 1995, ARVD was classified as a primary cardiomyopathy by the World Health Organization (Richardson et al., [11]). Thus, now classifying ACM as a cardiomyopathy (i.e., ARVC) rather than a dysplasia (i.e., ARVD). Even more recently, ARVC has shifted from its recognition as a primarily RV disease (i.e., ARVC) to include left-dominant (i.e., ALVC) and biventricular subtypes (i.e., ACM) as well (Saguner et al., [12]), prompting the use of the more general term arrhythmogenic cardiomyopathy (ACM). This review aims to discuss pathogenesis, clinical and pathological phenotypes, basic and translational research on the role of inflammation, and clinical trials aimed to prevent disease onset and progression.

Arrhythmic risk stratification in arrhythmogenic right ventricular cardiomyopathy.

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.

Unmasking the uncommon: bidirectional ventricular tachycardia in two rare paediatric cardiomyopathies.

We present two exceptional cases of 14-year-old girls diagnosed with rare cardiomyopathies (left ventricular non-compaction, and arrhythmogenic right ventricular cardiomyopathy), both presenting with the unusual finding of bidirectional ventricular tachycardia.

Isolated JUP plakoglobin gene mutation with left ventricular fibrosis in familial arrhythmogenic right ventricular cardiomyopathy.

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.