Programmed Ventricular Stimulation as an Additional Primary Prevention Risk Stratification Tool in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Study.

BACKGROUND: A novel risk calculator based on clinical characteristics and noninvasive tests that predicts the onset of clinical sustained ventricular arrhythmias (VA) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been proposed and validated by recent studies. It remains unknown whether programmed ventricular stimulation (PVS) provides additional prognostic value. METHODS: All patients with a definite ARVC diagnosis, no history of sustained VAs at diagnosis, and PVS performed at baseline were extracted from 6 international ARVC registries. The calculator-predicted risk for sustained VA (sustained or implantable cardioverter defibrillator treated ventricular tachycardia [VT] or fibrillation, [aborted] sudden cardiac arrest) was assessed in all patients. Independent and combined performance of the risk calculator and PVS on sustained VA were assessed during a 5-year follow-up period. RESULTS: Two hundred eighty-eight patients (41.0±14.5 years, 55.9% male, right ventricular ejection fraction 42.5±11.1%) were enrolled. At PVS, 137 (47.6%) patients had inducible ventricular tachycardia. During a median of 5.31 [2.89-10.17] years of follow-up, 83 (60.6%) patients with a positive PVS and 37 (24.5%) with a negative PVS experienced sustained VA (P<0.001). Inducible ventricular tachycardia predicted clinical sustained VA during the 5-year follow-up and remained an independent predictor after accounting for the calculator-predicted risk (HR, 2.52 [1.58-4.02]; P<0.001). Compared with ARVC risk calculator predictions in isolation (C-statistic 0.72), addition of PVS inducibility showed improved prediction of VA events (C-statistic 0.75; log-likelihood ratio for nested models, P<0.001). PVS inducibility had a 76% [67-84] sensitivity and 68% [61-74] specificity, corresponding to log-likelihood ratios of 2.3 and 0.36 for inducible (likelihood ratio+) and noninducible (likelihood ratio-) patients, respectively. In patients with a ARVC risk calculator-predicted risk of clinical VA events <25% during 5 years (ie, low/intermediate subgroup), PVS had a 92.6% negative predictive value. CONCLUSIONS: PVS significantly improved risk stratification above and beyond the calculator-predicted risk of VA in a primary prevention cohort of patients with ARVC, mainly for patients considered to be at low and intermediate risk by the clinical risk calculator.

Exercise and arrhythmic risk in TMEM43 p.S358L arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: High-level exercise has been associated with a malignant phenotype in desmosomal and genotype-negative forms of arrhythmogenic right ventricular cardiomyopathy (ARVC). This is the first study to examine this issue with ARVC secondary to the TMEM43 p.S358L mutation. OBJECTIVE: The purpose of this study was to evaluate the impact of exercise on arrhythmic risk and cardiac death in TMEM43 p.S358L ARVC. METHODS: Individuals with the TMEM43 p.S358L mutation enrolled in a prospective registry who had received a primary prevention implantable cardioverter-defibrillator (ICD) were invited to complete the modified Paffenbarger Physical Activity Questionnaire to assess their physical activity in the year before their ICD implantation. Time-to-event analyses using unadjusted and adjusted Cox proportional hazards models evaluated associations between physical activity and first appropriate ICD discharge secondary to malignant ventricular arrhythmia or cardiac death. RESULTS: In 80 subjects with the TMEM43 p.S358L mutation, exercise ≥9.0 metabolic equivalent of task (MET)-hours/day (high level) in the year before ICD implantation was associated with an adjusted 9.1-fold increased hazard of first appropriate ICD discharge (there were no deaths) relative to physical activity <9.0 MET-hours/day (moderate level) (95% confidence interval [CI] 3.3-24.6 MET-hours/day; P < .001). The median age from birth to first appropriate ICD discharge was 58.5 years (95% CI 56.5-60.5 years) vs 35.8 years (95% CI 28.2-43.4 years) (P < .001) in subjects in moderate- and high-level exercise groups, respectively. CONCLUSION: Exercise ≥9.0 MET-hours/day is associated with an increased risk of malignant ventricular arrhythmias in the TMEM43 p.S358L subtype of ARVC. Extrapolating these data, we suggest molecular testing be offered in early childhood to inform exercise choices reflective of the genotype.

Electrical Storm in ICD Recipients with Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Implantable cardioverter defibrillator (ICD) is the most important management for prevention of sudden cardiac death (SCD) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). However, some patients may receive multiple ICD therapies in a short period, a condition referred as "electrical storm" (ES). OBJECTIVES: This study aimed to determine the prevalence, therapeutic options, and prognostic implications of ES in ARVC patients with an ICD. METHODS: We retrospectively analyzed the baseline and follow-up data of 39 ARVC patients with an ICD. ES was defined as three or more separated episodes of ventricular tachycardia or ventricular fibrillation (VT/VF) within a 24-hour period. RESULTS: During a median follow-up of 49 months (range 6-225), 12 of 39 (31%) patients suffered at least one episode of ES. The interval between the first ES and the initial ICD implantation ranged from 1 month to 109 months, and ES was the first ICD discharge in three patients. The median number of VT/VF events per ES was four (range 3-39). Five patients experienced 20 episodes of ES that were treated by antitachycardia pacing only, while the other seven patients suffered shock therapies during ES. In three patients, ES required emergency hospitalization, and the repeatedly occurred VT/VF was finally subsided by intravenous amiodarone. There was no significant difference in actual survival between patients with and without such an event. CONCLUSIONS: ES is not rare in ARVC patients with an ICD for prevention of SCD, but it does not independently confer increased mortality. Intravenous amiodarone is effective in management of ES when VT/VF repeatedly occurred.

[Redetection of tachycardia in severe ventricular undersensing]. / Redetektion einer Tachykardie bei ausgeprägtem ventrikulären Undersensing.

In a 50-year-old patient with arrhythmogenic right ventricular cardiomyopathy (ARVC) and implantable cardioverter defibrillator (ICD) two shock discharges occurred after several ineffective attempts with antitachycardia pacing. The analysis of the stored electrograms shows a peculiarity of shocks with low energy, a problem of ICD therapy in ARVC, and the impact of committed shocks as opposed to non-committed shocks.

Risk stratification in arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic cardiomyopathy characterized by myocyte death and fibrofatty replacement mostly in the right ventricle. It is a leading cause of sudden cardiac death (SCD) in individuals under the age of 35 years. The main goal in the treatment of the disease is the prevention of SCD. An implantable cardioverter-defibrillator (ICD) is the only proven life-saving therapeutic option able to improve survival in ARVC patients. This therapy is not free from side effects and it accounts for a relatively high rate of morbidity because of the occurrence of inappropriate ICD interventions and of complications, both at implantation and during the follow-up. In recent years, the approach to ICD implantation has been changing on the basis of new emerging data on risk stratification. The usefulness of ICD implantation for secondary prevention has been definitively proven; the most challenging question is how to treat patients with no history of previous cardiac arrest or hemodynamically unstable ventricular tachycardia (VT). The value of ECG abnormalities, syncope, VT, and right/left ventricular involvement as predictors of SCD has been assessed in different studies with the purpose of better defining risk stratification in ARVC. Nevertheless, in spite of the growing amount of data, primary prevention in ARVC patients remains mostly an individual decision.

Multicenter experience with transvenous lead extraction in arrhythmogenic right ventricular cardiomyopathy (ARVC).

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is becoming a more commonly diagnosed entity with frequent need for coincident implantable cardioverter defibrillator (ICD) therapy. Given predominant right ventricular disease with thinning of the wall, there is concern regarding the safety of transvenous lead extraction (TLE) in ARVC. METHODS: We performed a retrospective study of consecutive patients with ARVC undergoing TLE of ICD leads at three high-volume centers. Patient and lead characteristics, indications, outcomes, and extraction sheath (ES) use were analyzed. RESULTS: Between 1999 and 2012, more than 2,000 lead extractions were performed at the three centers. Of these, 11 patients underwent 14 extractions meeting inclusion criteria. Mean implant duration was 74.5 months (range 6-140). In 11 patients, a total of 22 leads (16 high-voltage and six pace-sense leads) were extracted in 14 procedures. The cohort was 50% male with a mean age of 45 years (range, 25-56) and mean ejection fraction 55 ± 13%. The majority (64%) of leads were extracted due to lead malfunction, three patients had an ICD lead removed for exit block, and three patients underwent TLE for infectious complications (two local, one systemic). ES assistance with laser or mechanical cutting sheaths was employed in the vast majority of cases (85.7%). All leads were removed completely. There were no major procedural complications. In five cases, lead reimplantation encountered low-amplitude R waves requiring multiple attempted lead positions before final successful implant. CONCLUSIONS: This is the first reported series of TLE in ARVC patients. TLE can be performed safely and effectively in patients with ARVC by experienced operators at high-volume centers with a low complication rate.

Incidence and predictors of implantable cardioverter-defibrillator therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing implantable cardioverter-defibrillator implantation for primary prevention.

OBJECTIVES: The purpose of this study was to define the incidence and predictors of implantable cardioverter-defibrillator (ICD) therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) after placement of an ICD for primary prevention. BACKGROUND: Patients with a diagnosis of ARVD/C often receive an ICD for prevention of sudden cardiac death. METHODS: Patients (n = 84) from the Johns Hopkins registry with definite or probable ARVD/C who underwent ICD implantation for primary prevention were studied. Detailed phenotypic, genotype, and ICD event information was obtained and appropriate ICD therapies were adjudicated based on intracardiac electrograms. RESULTS: Over a mean follow-up of 4.7 ± 3.4 years, appropriate ICD therapy was seen in 40 patients (48%), of whom 16 (19%) received interventions for potentially fatal ventricular fibrillation/flutter episodes. Proband status (p < 0.001), inducibility at electrophysiologic study (p = 0.005), presence of nonsustained ventricular tachycardia (p < 0 .001), and Holter premature ventricular complex count >1,000/24 h (p = 0.024) were identified as significant predictors of appropriate ICD therapy. The 5-year survival free of appropriate ICD therapy for patients with 1, 2, 3, and 4 risk factors was 100%, 83%, 21%, and 15%, respectively. Inducibility at electrophysiologic study (hazard ratio: 4.5, 95% confidence interval: 1.4 to 15, p = 0.013) and nonsustained ventricular tachycardia (hazard ratio: 10.5, 95% confidence interval: 2.4 to 46.2, p = 0.002) remained as significant predictors on multivariable analysis. CONCLUSIONS: Nearly one-half of the ARVD/C patients with primary prevention ICD implantation experience appropriate ICD interventions. Inducibility at electrophysiologic study and nonsustained ventricular tachycardia are independent strong predictors of appropriate ICD therapy. An increase in ventricular ectopy burden was associated with progressively lower event-free (appropriate ICD interventions) survival. Incremental risk of ventricular arrhythmias and ICD therapy was observed with the presence of multiple risk factors.

Load-reducing therapy prevents development of arrhythmogenic right ventricular cardiomyopathy in plakoglobin-deficient mice.

OBJECTIVES: We used a murine model of arrhythmogenic right ventricular cardiomyopathy (ARVC) to test whether reducing ventricular load prevents or slows development of this cardiomyopathy. BACKGROUND: At present, no therapy exists to slow progression of ARVC. Genetically conferred dysfunction of the mechanical cell-cell connections, often associated with reduced expression of plakoglobin, is thought to cause ARVC. METHODS: Littermate pairs of heterozygous plakoglobin-deficient mice (plako(+/-)) and wild-type (WT) littermates underwent 7 weeks of endurance training (daily swimming). Mice were randomized to blinded load-reducing therapy (furosemide and nitrates) or placebo. RESULTS: Therapy prevented training-induced right ventricular (RV) enlargement in plako(+/-) mice (RV volume: untreated plako(+/-) 136 ± 5 µl; treated plako(+/-) 78 ± 5 µl; WT 81 ± 5 µl; p < 0.01 for untreated vs. WT and untreated vs. treated; mean ± SEM). In isolated, Langendorff-perfused hearts, ventricular tachycardias (VTs) were more often induced in untreated plako(+/-) hearts (15 of 25), than in treated plako(+/-) hearts (5 of 19) or in WT hearts (6 of 21, both p < 0.05). Epicardial mapping of the RV identified macro-re-entry as the mechanism of ventricular tachycardia. The RV longitudinal conduction velocity was reduced in untreated but not in treated plako(+/-) mice (p < 0.01 for untreated vs. WT and untreated vs. treated). Myocardial concentration of phosphorylated connexin43 was lower in plako(+/-) hearts with VTs compared with hearts without VTs and was reduced in untreated plako(+/-) compared with WT (both p < 0.05). Plako(+/-) hearts showed reduced myocardial plakoglobin concentration, whereas ß-catenin and N-cadherin concentration was not changed. CONCLUSIONS: Load-reducing therapy prevents training-induced development of ARVC in plako(+/-) mice.

Cardiomiopatia arritmogênica do ventrículo direito: [revisão] / Arrhythmogenic right ventricular cardiomyopathy: [review]

JUSTIFICATIVA E OBJETIVOS: Com frequência, atletas e adultos jovens são acometidos por morte súbita cardíaca (MSC). Há relatos na literatura de que a cardiomiopatia arritmogênica do ventrículo direito (CAVD) seja a doença mais frequente nesta população. Apesar de não se tratar de condição rara e ser o diagnóstic o essencial para a prevenção de morte súbita, ele é pouco realizado. O objetivo deste estudo foi descrever as características clínicas, diagnósticas e medidas de prevenção de morte súbita cardíaca relacionada à CAVD. CONTEÚDO: A CAVD é uma doença genética, de caráter familiar, caracterizada por substituição progressiva do miocárdio por tecido fibrogorduroso. Clinicamente manifesta-se por palpitações, síncope e, em alguns casos, morte súbita como manifestação inicial. O diagnóstico se faz por meio de critérios clínicos e de imagem, como ecocardiografia e ressonância nuclear magnética e por meio de biópsia endocárdica. O tratamento é baseado na prevenção de morte súbita cardíaca em pacientes de alto risco através do implante de cardiodesfibrilador implantável (CDI) e no uso de antiarrítmicos para diminuição da incidência de arritmias. A prática de esportes de competição deve ser evitada pelo maior risco de morte cardíaca súbita. CONCLUSÃO: A CAVD é uma entidade nosológica frequente, responsável por morte cardíaca súbita em adultos jovens e atletas. O implante de CDI parece prevenir estes episódios. Necessita de maior notoriedade para maior frequência diagnóstica e prevenção precoce de morte cardíaca súbita.

BACKGROUND AND OBJECTIVES: Frequently, athletes and adults are attacked by cardiac sudden death (CSD). Thereare stories at the literature that arrhythmogenic right ventricular cardiomyopathy (ARVC) is the most frequent illness atthis population, being its important diagnosis for the prevention of cardiac sudden death, however little carried through. The objective of this study was to describe the clinical characteristics, diagnostic and measures of prevention of sudde ndeath in the ARVD. CONTENTS: The ARVD is a genetic illness, with a familiar character, characterized by substitution of the myocardium forfibrofatty tissue. It manifests by palpitations, syncope and, insome cases, cardiac sudden death as initial manifestation. The diagnosis means of clinical criteria and image, as echocardiography and magnetic nuclear resonance, as well as by means of endocardic biopsies. The treatment bases on the prevention of cardiac sudden death in patients of high risk through the implantation of implantable cardiodesfibrilador (ICD) and in the use of antiarrhythmic for reduction of the incidence of arrhythmias. The practical of competition sports must be prevented by the biggestrisk of cardiac sudden death. CONCLUSION: The ARVD is responsible for cardiac sudde ndeath in young adult's e athletes. The implantation of ICD seems to prevent these episodes. Soon, it needs bigger notoriety formost frequently diagnostic and precocious prevention of cardiac sudden death.

Avaliação por eletrocardiografia contínua (holter) em cães da raça Pastor Alemão praticantes de atividade física regular / Ambulatory electrocardiography (Holter) evaluation in physically active German shepherd dogs

The pattern for ambulatory electrocardiography was evaluated in 25 healthy German Shepherd dogs. The influences of gender, age, and physical activity in HR maximum, mean, and minimum (HRmx, HRme, and HRmin, respectively) were studied. The physically active dogs (PA) showed lower HRme than sedentary animals (S) (P=0.03), whereas HRmx and HRmin were not altered (P=0.06 and P=0.65, respectively). The HRme was 80.89±13.85 for PA and 112.94±35.71 for S. No effect of gender and age on HR was observed. It is possible to state that the physical activity can modulate the sinus node of the dogs.

Arrhythmogenic right ventricular cardiomyopathy as lethal complication factor after cardiac surgery.

In patients with arrhythmogenic right ventricular dysplasia (ARVD), the right ventricular myocardium histologically discloses atrophy paralleled by fibrofatty or fatty replacement. Apoptosis is believed to be a putative major pathogenetic mechanism. Altogether, our knowledge of genetics, etiology and pathophysiology of ARVD has increased impressively in the last few years, and effective genetic tests now principally would be possible. Nevertheless, due to often uncharacteristic or even lacking symptoms, clinical diagnosis may be very difficult and could not be made during lifetime of patient presented here, partly due to additional, independent cardiac problems. The question of an effective preoperative diagnostic regimen for cardiosurgical interventions remains and seems to be currently open.

Arrhythmogenic right ventricular cardiomyopathy: diagnosis and risk stratification.

Arrhythmogenic right ventricular cardiomyopathy (ARVCM) is a genetically determined disease characterized by the progressive replacement of cardiomyocytes by fibrofatty tissue, predominantly in the right ventricle. It leads to electrical instability and is therefore a major cause of sudden cardiac death (SCD) in apparently healthy young individuals, particularly in athletes. The diagnosis of ARVCM can be challenging and is based on a set of major and minor criteria which include structural, functional, histological, imaging, electrocardiographic and anamnestic parameters. ARVCM can be diagnosed, when two major criteria, or one major and two minor criteria, or four minor criteria from different categories are present. An implantable cardioverter defibrillator (ICD) should be used in patients who were resuscitated from SCD or who present with sustained ventricular tachycardia or otherwise unexplained syncope. The role of ICD therapy in primary prevention of SCD is a matter of ongoing debate and has to be decided on an individualized basis. Due to the familial accumulation of the disease, the screening of relatives is important. For the symptomatic treatment of arrhythmias, beta-blockers, sotalol, amiodarone and catheter ablation can be used. Arrhythmias in patients with ARVCM often occur in conjunction with physical exercise. Patients with ARVCM should therefore abstain from competitive sports or leisure-time activities where any possible loss of consciousness poses an increased hazard (scuba diving, hang gliding, parachuting, etc.).

Arrhythmogenic right ventricular cardiomyopathy in athletes: diagnosis, management, and recommendations for sport activity.

This article examines the role of arrhythmogenic right ventricular cardiomyopathy/dysplasia in causing sudden death in young competitive athletes and suggests a prevention strategy based on identification of affected athletes at preparticipation screening. Systematic cardiovascular screening (including 12-lead ECG) of all subjects embarking on sports activity has the potential to identify those athletes at risk and to reduce mortality.