Early Preventive Treatment With Enalapril Improves Cardiac Function and Delays Mortality in Mice With Arrhythmogenic Right Ventricular Cardiomyopathy Type 5.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) is an inherited cardiac disease with complete penetrance and an aggressive clinical course caused by mutations in TMEM43 (transmembrane protein 43). There is no cure for ARVC5 and palliative treatment is started once the phenotype is present. A transgenic mouse model of ARVC5 expressing human TMEM43-S358L (TMEM43mut) recapitulates the human disease, enabling the exploration of preventive treatments. The aim of this study is to determine whether preventive treatment with heart failure drugs (ß-blockers, ACE [angiotensin-converting enzyme] inhibitors, mineralocorticoid-receptor antagonists) improves the disease course of ARVC5 in TMEM43mut mice. METHODS: TMEM43mut male/female mice were treated with metoprolol (ß-blockers), enalapril (ACE inhibitor), spironolactone (mineralocorticoid-receptor antagonist), ACE inhibitor + mineralocorticoid-receptor antagonist, ACE inhibitor + mineralocorticoid-receptor antagonist + ß-blockers or left untreated. Drugs were initiated at 3 weeks of age, before ARVC5 phenotype, and serial ECG and echocardiograms were performed. RESULTS: TMEM43mut mice treated with enalapril showed a significantly increased median survival compared with untreated mice (26 versus 21 weeks; P=0.003). Enalapril-treated mice also exhibited increased left ventricular ejection fraction at 4 months compared with controls (37.0% versus 24.9%; P=0.004), shorter QRS duration and reduced left ventricle fibrosis. Combined regimens including enalapril also showed positive effects. Metoprolol decreased QRS voltage prematurely and resulted in a nonsignificant decrease in left ventricular ejection fraction compared with untreated TMEM43mut mice. CONCLUSIONS: Preventive enalapril-based regimens reduced fibrosis, improved ECG, echocardiographic parameters and survival of ARVC5 mice. Early metoprolol did not show positive effects and caused premature ECG abnormalities. Our findings pave the way to consider prophylactic enalapril in asymptomatic ARVC5 genetic carriers.

Cardiomiopatia arritmogênica do ventrículo direito em maratonista: relato de caso / Arrhythmogenic right ventricular cardiomyopathy in marathon runners: case report

A cardiomiopatia arritmogênica do ventrículo direito é uma desordem hereditária caracterizada pela substituição fibrogordurosa do músculo cardíaco. O manejo clínico busca reduzir os riscos de morte súbita e melhorar a qualidade de vida, aliviando os sintomas arrítmicos e de insuficiência cardíaca. O ecocardiograma é o exame inicial para a investigação da cardiomiopatia arritmogênica do ventrículo direito, podendo apresentar dilatação das câmaras direitas e disfunção sistólica do ventrículo direito. Este relato chama atenção por envolver o diagnóstico de cardiomiopatia arritmogênica do ventrículo direito em paciente atleta. Mulher, 47 anos, maratonista, sem história familiar de morte súbita cardíaca, deu entrada na emergência com palpitação associada à pré-síncope. O eletrocardiograma da admissão mostrava taquicardia ventricular. O ecocardiograma revelou aumento de câmaras cardíacas direitas e disfunção sistólica do ventrículo direito. O cateterismo cardíaco não evidenciou doença coronária obstrutiva. A paciente foi orientada acerca da necessidade de suspensão de atividades físicas, porém, 3 meses depois, foi readmitida com instabilidade hemodinâmica por nova taquicardia ventricular, tendo sido cardiovertida. Realizou ressonância cardíaca, que evidenciou áreas de discinesia e formação de microaneurismas em ventrículo direito. Foi diagnosticada com cardiomiopatia arritmogênica do ventrículo direito, tendo sido com cardioversor desfibrilador implantável, amiodarona e betabloqueador. A diferenciação entre a cardiomiopatia arritmogênica do ventrículo direito e o coração do atleta representa um desafio, devido à sobreposição de alterações estruturais que coexistem nessas entidades, daí a importância da análise integrada de fatores clínicos, eletrocardiográficos e morfofuncionais.(AU)

Autoptic findings of sudden cardiac death (SCD) in patients with arrhythmogenic ventricular cardiomiopathy (AVC) from left ventricle and biventricular involvement.

OBJECTIVES: To evaluate autoptic histopathological findings of arrhythmogenic ventricular cardiomyopathy (AVC) as major cause of sudden cardiac death (SCD) in young adults. BACKGROUND: According to Heart Rhythm Society (HRS)'s international consensus, histological criteria for AVC diagnosis include a progressive myocardial atrophy of the right ventricle characterized by a transmural fatty or fibrofatty replacement in a segmental or diffuse pattern (residual myocytes <60 % vs 60-75 % by morphometric analysis) explaining the electrical instability with increased risk of SCD. However, there is increasing evidence for atypical patterns of localizations and percentage of fibrofatty replacement suggesting the need to update histopathological features of AVC. METHODS: Histology examination of ventricles, atria, and septum was performed on 10 autopsy of SCD due to AVC. Staining with hematoxylin-eosin and PicroSirius Red/Fast Green were performed on the heart samples to identify specific fibrofatty patterns. RESULTS: Our analysis showed that: 1) myocardial replacement by a diffuse segmental fatty or fibro-fatty tissue characterized right and left ventricles as well as atrial walls; 2) the degree of fibrofatty tissue replacement was less than 40 % both in left ventricle (n = 4, 40 %) and biventricular (n = 6, 60 %) localization; 3) perivascular fibrosis, inflammatory infiltrate, areas of hypertrophy and/or areas of coagulative necrosis as signs of hypoxic damage in the first stage. CONCLUSIONS: We confirmed prior evidence for fibrofatty replacement both in biventricular and septal localizations. Importantly, we observed a less degree (<40 %) of fibrofatty replacement as compared to current guidelines. This supports the need to further explore the histological patterns of fibrofatty infiltration in a larger study population to improve the histological diagnostic criteria of AVC.

Arrhythmogenic Cardiomyopathy and Sports Activity.

Arrhythmogenic right-ventricular cardiomyopathy (ARVC) is a genetically determined heart disease characterized by progressive myocyte death and substitution by fibrofatty tissue. Life-threatening ventricular arrhythmias may occur during the course of the disease and are distinctively triggered by sports activity: for this reason, ARVC is one of the leading causes of sudden death in the athlete. Early identification of affected athletes by preparticipation screening in the pre-symptomatic phase is essential, but differential diagnosis with the athlete's heart may be challenging. Variants with predominant involvement of the left ventricle are difficult to diagnose unless cardiac magnetic resonance is performed. Athletes with overt ARVC or asymptomatic carriers of pathological gene mutations, including those with an implantable cardioverter defibrillator, should refrain from competitive sports, while a moderate-intensity recreational physical activity appears safe.

Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification and therapy.

Arrhythmogenic cardiomyopathy (ACM) is a life-threatening cardiac disease caused by mutations in genes predominantly encoding for desmosomal proteins that lead to alterations in the molecular composition of the intercalated disc. ACM is characterized by progressive replacement of cardiomyocytes by fibrofatty tissue, ventricular dilatation, cardiac dysfunction, and heart failure but mostly dominated by the occurrence of life-threatening arrhythmias and sudden cardiac death (SCD). As SCD appears mostly in apparently healthy young individuals, there is a demand for better risk stratification of suspected ACM mutation carriers. Moreover, disease severity, progression, and outcome are highly variable in patients with ACM. In this review, we discuss the aetiology of ACM with a focus on pro-arrhythmic disease mechanisms in the early concealed phase of the disease. We summarize potential new biomarkers which might be useful for risk stratification and prediction of disease course. Finally, we explore novel therapeutic strategies to prevent arrhythmias and SCD in the early stages of ACM.

Special Article - Exercise-induced right ventricular injury or arrhythmogenic cardiomyopathy (ACM): The bright side and the dark side of the moon.

There is still debate on the range of normal physiologic changes of the right ventricle or ventricular (RV) function in athletes. Genetic links to arrhythmogenic cardiomyopathy (ACM) are well-established. There is no current consensus on the importance of extensive exercise and exercise-induced injury to the RV. During the intensive exercise of endurance sports, the cardiac structures adapt to athletic load over time. Some athletes develop RV cardiomyopathy possibly caused by genetic predisposition, whilst others develop arrhythmias from the RV. Endurance sports lead to increased volume and pressure load in both ventricles and increased myocardial mass. The extent of volume increase and changes in myocardial structure contribute to impairment of RV function and pose a challenge in cardiovascular sports medicine. Genetic predisposition to ACM may play an important role in the risk of sudden cardiac death of athletes. In this review, we discuss and evaluate existing results and opinions. Intensive training in competitive dynamic/power and endurance sports leads to specific RV adaptation, but physiological adaptation without genetic predisposition does not necessarily lead to severe complications in endurance sports. Discriminating between physiological adaptation and pathological form of ACM or RV impairment provoked by reinforced exercise presents a challenge to clinical sports cardiologists.

Exercise and Arrhythmogenic Right Ventricular Cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a group of cardiomyopathies associated with ventricular arrhythmias predominantly arising from the right ventricle, sudden cardiac death and right ventricular failure, caused largely due to inherited mutations in proteins of the desmosomal complex. Whilst long recognised as a cause of sudden cardiac death (SCD) during exercise, it has recently been recognised that intense and prolonged exercise can worsen the disease resulting in earlier and more severe phenotypic expression. Changes in cardiac structure and function as a result of exercise training also pose challenges with diagnosis as enlargement of the right ventricle is commonly seen in endurance athletes. Advice regarding restriction of exercise is an important part of patient management, not only of those with established disease, but also in individuals known to carry gene mutations associated with development of ARVC.

Characterization of Structural Changes in Arrhythmogenic Right Ventricular Cardiomyopathy With Recurrent Ventricular Tachycardia After Ablation: Insights From Repeat Electroanatomic Voltage Mapping.

BACKGROUND: Data characterizing structural changes of arrhythmogenic right ventricular (RV) cardiomyopathy are limited. METHODS: Patients presenting with left bundle branch block ventricular tachycardia in the setting of arrhythmogenic RV cardiomyopathy with procedures separated by at least 9 months were included. RESULTS: Nineteen consecutive patients (84% males; mean age 39±15 years [range, 20-76 years]) were included. All 19 patients underwent 2 detailed sinus rhythm electroanatomic endocardial voltage maps (average 385±177 points per map; range, 93-847 points). Time interval between the initial and repeat ablation procedures was mean 50±37 months (range, 9-162). No significant progression of voltage was observed (bipolar: 38 cm2 [interquartile range (IQR), 25-54] versus 53 cm2 [IQR, 25-65], P=0.09; unipolar: 116 cm2 [IQR, 61-209] versus 159 cm2 [IQR, 73-204], P=0.36) for the entire study group. There was a significant increase in RV volumes (percentage increase, 28%; 206 mL [IQR, 170-253] versus 263 mL [IQR, 204-294], P<0.001) for the entire study population. Larger scars at baseline but not changes over time were associated with a significant increase in RV volume (bipolar: Spearman ρ, 0.6965, P=0.006; unipolar: Spearman ρ, 0.5743, P=0.03). Most patients with progressive RV dilatation (8/14, 57%) had moderate (2 patients) or severe (6 patients) tricuspid regurgitation recorded at either initial or repeat ablation procedure. CONCLUSIONS: In patients with arrhythmogenic RV cardiomyopathy presenting with recurrent ventricular tachycardia, >10% increase in RV endocardial surface area of bipolar voltage consistent with scar is uncommon during the intermediate term. Most recurrent ventricular tachycardias are localized to regions of prior defined scar. Voltage indexed scar area at baseline but not changes in scar over time is associated with progressive increase in RV size and is consistent with adverse remodeling but not scar progression. Marked tricuspid regurgitation is frequently present in patients with arrhythmogenic RV cardiomyopathy who have progressive RV dilation.

[Analysis of 30 cases of inherited cardiac arrhythmia syndrome in children].

Objective: To analyze and summarize the diagnosis and treatment experience of common inherited cardiac arrhythmia syndrome in pediatric patients, and explore the most appropriate therapy. Methods: A retrospective review identified 30 pediatric cases (19 males, 11 females) diagnosed with long QT syndrome (LQTS), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), hypertrophic cardiomyopathy (HCM), arrhythmogenc right ventricular cardiomyopathy (ARVC) from January 2008 to December 2018 in the Pediatric Cardiology Department, Guangdong Provincial People's Hospital. Data obtained included the diagnosis, treatment and follow-up outcome. Results: The most common inherited cardiac arrhythmia syndromes were LQTS (n=14) including 1 case with epilepsy, CPVT (n=5), HCM (n=7), ARVC (n=1), and BrS (n=3). Twenty-seven cases were admitted to hospital due to syncope, whereas the remaining 3 cases of BrS had not presented with syncope before admission. The average onset age of inherited arrhythmia was (10.0±3.3) years. Genetic testing was performed on 20 patients. The median follow-up time was 40 months. Among 15 patients who underwent implantable cardioverter defibrillator (ICD) and survived, 2 patients had frequent ICD discharge. One patient underwent radiofrequency ablation, and the other one received left cardiac sympathetic denervation and an increased ICD defibrillation threshold, and the number of ICD discharge was significantly reduced. Among 10 patients who received drug therapy, 4 patients including two patients who discontinued treatment without advices died. Two patients whose parents refused treatment died, 1 case diagnosed with unexplained sudden cerebral death, and the remaining 2 cases without indication for drug therapy survived without any treatment. Conclusions: Mortality rate is high in pediatric patients with inherited cardiac arrhythmia and syncope. The therapeutic effect of drugs are not satisfactory, ICD implantation is the most effective treatment to prevent sudden cardiac death currently, but the postoperative frequent discharge should be brought to the forefront and handled in time.

Clinical Differences in Japanese Patients Between Brugada Syndrome and Arrhythmogenic Right Ventricular Cardiomyopathy With Long-Term Follow-Up.

Some Brugada syndrome (BrS) patients have been suspected of being in the initial state of arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aimed to clarify the electrocardiographic (ECG) and clinical differences between BrS and ARVC in long-term follow-up (mean 11.9 ± 6.3 years). A total of 50 BrS and 65 ARVC patients with fatal ventricular tachyarrhythmia (VTA) were evaluated according to the revised Task Force Criteria for ARVC. Based on the current diagnostic criteria concerning electrocardiographic, repolarization abnormality was positive in 2.0% and 2.6% of BrS patients at baseline and follow-up, and depolarization abnormality was positive in 6.0% and 12.8% of BrS patients at baseline and follow-up, respectively. At baseline, none of the BrS patients were definitively diagnosed with ARVC. Considering patients' lives since birth, Kaplan-Meier analysis revealed that age at first VTA attack showed the same tendency between the groups (BrS: mean 42.2 ± 12.5 years old vs ARVC: mean 44.8 ± 13.7 years old, log-rank p = 0.123). Moreover, the incidence of VTA recurrence was similar between the groups during follow-up (log-rank p = 0.906). Incidence of sustained monomorphic ventricular tachycardia was significantly higher in ARVC than in BrS whereas the opposite was true for ventricular fibrillation (log-rank p <0.001 and p <0.001, respectively). None of the diagnoses of BrS patients were changed to ARVC during follow-up. During long-term follow-up, although age at first VTA attack and VTA recurrence were similar, BrS consistently exhibited features that differed from those of ARVC.

A new prediction model for ventricular arrhythmias in arrhythmogenic right ventricular cardiomyopathy.

AIMS: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is characterized by ventricular arrhythmias (VAs) and sudden cardiac death (SCD). We aimed to develop a model for individualized prediction of incident VA/SCD in ARVC patients. METHODS AND RESULTS: Five hundred and twenty-eight patients with a definite diagnosis and no history of sustained VAs/SCD at baseline, aged 38.2 ± 15.5 years, 44.7% male, were enrolled from five registries in North America and Europe. Over 4.83 (interquartile range 2.44-9.33) years of follow-up, 146 (27.7%) experienced sustained VA, defined as SCD, aborted SCD, sustained ventricular tachycardia, or appropriate implantable cardioverter-defibrillator (ICD) therapy. A prediction model estimating annual VA risk was developed using Cox regression with internal validation. Eight potential predictors were pre-specified: age, sex, cardiac syncope in the prior 6 months, non-sustained ventricular tachycardia, number of premature ventricular complexes in 24 h, number of leads with T-wave inversion, and right and left ventricular ejection fractions (LVEFs). All except LVEF were retained in the final model. The model accurately distinguished patients with and without events, with an optimism-corrected C-index of 0.77 [95% confidence interval (CI) 0.73-0.81] and minimal over-optimism [calibration slope of 0.93 (95% CI 0.92-0.95)]. By decision curve analysis, the clinical benefit of the model was superior to a current consensus-based ICD placement algorithm with a 20.6% reduction of ICD placements with the same proportion of protected patients (P < 0.001). CONCLUSION: Using the largest cohort of patients with ARVC and no prior VA, a prediction model using readily available clinical parameters was devised to estimate VA risk and guide decisions regarding primary prevention ICDs (www.arvcrisk.com).

Sudden Death and Left Ventricular Involvement in Arrhythmogenic Cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is an inherited heart muscle disorder characterized by myocardial fibrofatty replacement and an increased risk of sudden cardiac death (SCD). Originally described as a right ventricular disease, ACM is increasingly recognized as a biventricular entity. We evaluated pathological, genetic, and clinical associations in a large SCD cohort. METHODS: We investigated 5205 consecutive cases of SCD referred to a national cardiac pathology center between 1994 and 2018. Hearts and tissue blocks were examined by expert cardiac pathologists. After comprehensive histological evaluation, 202 cases (4%) were diagnosed with ACM. Of these, 15 (7%) were diagnosed antemortem with dilated cardiomyopathy (n=8) or ACM (n=7). Previous symptoms, medical history, circumstances of death, and participation in competitive sport were recorded. Postmortem genetic testing was undertaken in 24 of 202 (12%). Rare genetic variants were classified according to American College of Medical Genetics and Genomics criteria. RESULTS: Of 202 ACM decedents (35.4±13.2 years; 82% male), no previous cardiac symptoms were reported in 157 (78%). Forty-one decedents (41/202; 20%) had been participants in competitive sport. The adjusted odds of dying during physical exertion were higher in men than in women (odds ratio, 4.58; 95% CI, 1.54-13.68; P=0.006) and in competitive athletes in comparison with nonathletes (odds ratio, 16.62; 95% CI, 5.39-51.24; P<0.001). None of the decedents with an antemortem diagnosis of dilated cardiomyopathy fulfilled definite 2010 Task Force criteria. The macroscopic appearance of the heart was normal in 40 of 202 (20%) cases. There was left ventricular histopathologic involvement in 176 of 202 (87%). Isolated right ventricular disease was seen in 13%, isolated left ventricular disease in 17%, and biventricular involvement in 70%. Among whole hearts, the most common areas of fibrofatty infiltration were the left ventricular posterobasal (68%) and anterolateral walls (58%). Postmortem genetic testing yielded pathogenic variants in ACM-related genes in 6 of 24 (25%) decedents. CONCLUSIONS: SCD attributable to ACM affects men predominantly, most commonly occurring during exertion in athletic individuals in the absence of previous reported cardiac symptoms. Left ventricular involvement is observed in the vast majority of SCD cases diagnosed with ACM at autopsy. Current Task Force criteria may fail to diagnose biventricular ACM before death.

Cardiac sympathectomy for refractory ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: The sympathetic nervous system plays an important role in arrhythmogenesis in arrhythmogenic right ventricular cardiomyopathy (ARVC). Sudden cardiac death commonly occurs during exertion, and ß-blockers are associated with a reduction in arrhythmia burden. Bilateral cardiac sympathetic denervation (BCSD) has been shown to reduce implantable cardioverter-defibrillator (ICD) shocks in patients with structural heart disease and refractory ventricular tachycardia (VT); however, data in ARVC are sparse. OBJECTIVE: The purpose of this study was to evaluate the role of BCSD in patients with ARVC and refractory VT. METHODS: Consecutive patients with ARVC who underwent BCSD because of refractory VT were included. Number of ICD shocks, sustained VT episodes, VT storm, and antiarrhythmic therapy were assessed and compared before and after the intervention. VT-free survival rate, death, and heart transplantation were also evaluated. RESULTS: Eight patients with ARVC (mean age 32 ± 20 years; 3 men [38%]) underwent sympathectomy for recurrent VT. All patients failed catheter ablation, and 50% had a desmosomal mutation identified. Procedural complications included neuropathic pain, paravertebral venous plexus injury, and pneumothorax. Over a mean follow-up of 1.9 ± 0.9 years, 5 patients (63%) had no VT recurrence. BCSD significantly reduced the number of ICD shocks or sustained VT compared with 1-year pre-BCSD (mean 12.6 ± 18.2 and median 6.5 [interquartile range 4.5-10.5] pre-BCSD vs 0.9 ± 1.4 and 0 [interquartile range 0-1.5] post-BCSD; P = .011). Most of the patients (88%) were on ß-blocker therapy alone at the end of follow-up. One patient underwent heart transplantation because of heart failure, and no deaths occurred. CONCLUSION: BCSD may be an effective option for patients with ARVC and refractory ventricular arrhythmia who have failed conventional treatment modalities.

Diagnostic and therapeutic strategies for arrhythmogenic right ventricular dysplasia/cardiomyopathy patient.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is a rare inherited heart muscle disease characterized by ventricular tachyarrhythmia, predominant right ventricular dysfunction, and sudden cardiac death. Its pathophysiology involves close interaction between genetic mutations and exposure to physical activity. Mutations in genes encoding desmosomal protein are the most common genetic basis. Genetic testing plays important roles in diagnosis and screening of family members. Syncope, palpitation, and lightheadedness are the most common symptoms. The 2010 Task Force Criteria is the standard for diagnosis today. Implantation of a defibrillator in high-risk patients is the only therapy that provides adequate protection against sudden death. Selection of patients who are best candidates for defibrillator implantation is challenging. Exercise restriction is critical in affected individuals and at-risk family members. Antiarrhythmic drugs and ventricular tachycardia ablation are valuable but palliative components of the management. This review focuses on the current diagnostic and therapeutic strategies in ARVD/C and outlines the future area of development in this field.

Can abnormal dispersion of ventricular repolarization be a predictor of mortality in arrhythmogenic right ventricular cardiomyopathy: The importance of Tp-e interval.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy characterized by ventricular arrhythmias and specific ventricular pathology. Repolarization abnormalities, the significant contributor to life-threatening arrhythmias and mortality, are frequently observed ECG changes in patients with ARVC. This study aimed to evaluate the changes in Tp-e interval, Tp-e/QT, Tp-e/QTc ratio, and traditional electrocardiographic features of electrical dispersion in patients with ARVC. METHODS: A total of 105 participants were enrolled in the current study. The ARVC group consisted of 40 subjects (30 men, with a median of 35 (26-41) years), and the control group included of 65 age and sex-matched individuals (42 men, with a median of 37 (24-45) years). The Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were measured by the 12-lead electrocardiogram. RESULTS: Tp-e interval, cTp-e interval, Tp-e/QT, and Tp-e/QTc ratio were significantly higher in ARVC patients compared to the control group (all p < 0.001). Tp-e interval, cTp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were significantly increased in deceased ARVC patients compared to the survival group (p = 0.038, p < 0.001, p = 0.006, p = 0.032, respectively). In the multivariate analysis, RV-FAC and cTp-e interval level (p < 0.05 for each parameter) were associated with all-cause mortality [odds ratio 1.747 95% CI (1.012-3.018); p = 0.045 and odds ratio 1.166, 95% CI (1.017-1.336); p = 0.027, respectively]. CONCLUSION: Tp-e interval, cTp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were prolonged in patients with NC. We revealed that abnormal dispersion of ventricular repolarization suggests the increased risk of mortality in ARVC.

Prevalence of 18F-fluorodeoxyglucose positron emission tomography abnormalities in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disease that causes sudden cardiac death in the young. Inflammatory myocardial infiltrates have been described at autopsy and on biopsy, but there are few data on the presence of myocarditis in living patients with ARVC using non-invasive imaging techniques. FDG-PET is a validated technique for detecting myocardial inflammation in clinically suspected myocarditis. We aimed to determine the prevalence of myocardial inflammation in patients with ARVC using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS AND RESULTS: We performed a retrospective analysis of a single centre cohort of patients with ARVC referred for FDG-PET scans between 2012 and 2017 for investigation of symptoms or suspected device infection. Sixteen patients (12 male; age 42 ±â€¯13 years) with a definite diagnosis of ARVC were identified. Seven had positive FDG-PET scans, two of whom had cardiac sarcoidosis on endomyocardial biopsy. Of the remaining five, two carried pathogenic desmoplakin mutations. FDG uptake was found in the left ventricular myocardium in all cases. One patient also had right ventricular uptake. CONCLUSION: In this exploratory study, we show that some patients with ARVC have evidence for myocardial inflammation on FDG-PET, suggesting that myocarditis plays a role in disease pathogenesis.

Diagnostic Differentiation Between Arrhythmogenic Cardiomyopathy and Athlete's Heart by Using Imaging.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an important cause of sudden cardiac death (SCD) in youth and athletes. In the last decade, several studies focused on right ventricular (RV) remodeling in athletes and revealed that features of the physiological adaptation of the right heart to training, such as RV dilation, may overlap with those of ARVC. Therefore, a careful multiparametric evaluation is required for differential diagnosis in order to avoid false diagnosis of ARVC or, in contrast, fail to identify the risk of causing SCD. This review summarizes physiological adaptation of the RV to exercise and describes features that could help distinguishing between athlete's heart and ARVC.

Arrhythmic outcome of arrhythmogenic right ventricular cardiomyopathy patients without implantable defibrillators.

BACKGROUND: Implantable defibrillators (ICD) are an important therapy for arrhythmogenic right ventricular cardiomyopathy (ARVC) patients at high risk of sudden death. Given the high appropriate ICD therapy rate, some have argued that the mere act of implanting an ICD inflates the malignant arrhythmia rate in ARVC. OBJECTIVE: To report the arrhythmic course of ARVC patients without ICDs at the fulfillment of the 2010 Task Force Criteria and explore predictors of malignant ventricular arrhythmias. METHODS: We included 131 definite ARVC patients (age 32 ± 15 years, male 39%, proband 50%) either without ICDs (N  =  47) or receiving an ICD at least 6 months after the fulfillment of the diagnostic criteria. The primary outcome was a composite of cardiac arrest (both resuscitated successfully and unsuccessfully) and sustained ventricular tachyarrhythmias (cycle length< 600 milliseconds, at least 30 seconds or requiring an intervention for termination). RESULTS: At the fulfillment of the diagnostic criteria, ICDs were not recommended to 59 (45%) patients and declined by 22 (17%) patients. Forty (31%) patients were not recognized as having ARVC by the treating physicians. Over 8 (interquartile interval: 3-12) years, 38 (29%) patients had primary outcomes (8 cardiac arrests [3 died] and 30 sustained ventricular arrhythmias) while not having ICDs. The 1-year and 5-year event-free survival was 92% and 72%. Spontaneous sustained ventricular arrhythmias, cardiac syncope, men, proband, and inducibility in electrophysiology study were significantly associated with the primary outcome. CONCLUSION: In a contemporary cohort, a considerable risk of malignant arrhythmias existed in ARVC when ICDs were not implanted.

Risk Stratification in Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia Without an Implantable Cardioverter-Defibrillator.

OBJECTIVES: The purpose of this study was to identify clinical factors associated with arrhythmic events and sudden cardiac death (SCD), and to evaluate the prognostic value of electrophysiological study (EPS) in arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) patients without implantable cardioverter-defibrillators (ICDs). BACKGROUND: ARVC/D is an inherited cardiomyopathy characterized by a risk of SCD. Few studies have evaluated predictive factors of ventricular arrhythmias (VAs) in patients without ICDs. METHODS: Between 2000 and 2010, all consecutive patients with ARVC/D without ICDs and with EPS at diagnosis were enrolled. Patients that received an ICD during follow-up were censored at the date of implantation, and in that case, only VAs that occurred before ICD implantation were analyzed. Risk factors for any VA event were determined by Cox regression. Patients that only experienced SCD or aborted cardiac arrest (ACA) were reported. RESULTS: A total of 137 consecutive patients (78% male) diagnosed with ARVC/D without ICD were enrolled. 31% had sustained ventricular tachycardia at diagnosis. After mean follow-up of 42 ± 31 months, 19 patients experienced an episode of sustained VA and 5 patients experienced a SCD/ACA. No event occurred in asymptomatic patients. Left ventricular ejection fraction ≤50% (p = 0.024), positive EPS (p = 0.017), and physical activity >6 h/week (p = 0.025) were independently associated with occurrence of VAs. SCD/ACA exclusively occurred in male probands with definite diagnosis and syncope. CONCLUSIONS: In this cohort of ARVC/D patients without ICD, left ventricular ejection fraction ≤50%, positive EPS, and physical activity >6 h/week were independent predictors of VAs, whereas asymptomatic patients at diagnosis were at low risk. EPS predicted all VAs but had limited value to predict SCD/ACA.