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 20.3% 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).

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).

Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations.

The underlying genetic etiology of rhabdomyolysis remains elusive in a significant fraction of individuals presenting with recurrent metabolic crises and muscle weakness. Using exome sequencing, we identified bi-allelic mutations in TANGO2 encoding transport and Golgi organization 2 homolog (Drosophila) in 12 subjects with episodic rhabdomyolysis, hypoglycemia, hyperammonemia, and susceptibility to life-threatening cardiac tachyarrhythmias. A recurrent homozygous c.460G>A (p.Gly154Arg) mutation was found in four unrelated individuals of Hispanic/Latino origin, and a homozygous ∼34 kb deletion affecting exons 3-9 was observed in two families of European ancestry. One individual of mixed Hispanic/European descent was found to be compound heterozygous for c.460G>A (p.Gly154Arg) and the deletion of exons 3-9. Additionally, a homozygous exons 4-6 deletion was identified in a consanguineous Middle Eastern Arab family. No homozygotes have been reported for these changes in control databases. Fibroblasts derived from a subject with the recurrent c.460G>A (p.Gly154Arg) mutation showed evidence of increased endoplasmic reticulum stress and a reduction in Golgi volume density in comparison to control. Our results show that the c.460G>A (p.Gly154Arg) mutation and the exons 3-9 heterozygous deletion in TANGO2 are recurrent pathogenic alleles present in the Latino/Hispanic and European populations, respectively, causing considerable morbidity in the homozygotes in these populations.

Genetic aetiologies should be considered in paediatric cases of acute heart failure presumed to be myocarditis.

There are a variety of causes of acute heart failure in children including myocarditis, genetic/metabolic conditions, and congenital heart defects. In cases with a structurally normal heart and a negative personal and family history, myocarditis is often presumed to be the cause, but we hypothesise that genetic disorders contribute to a significant portion of these cases. We reviewed our cases of children who presented with acute heart failure and underwent genetic testing from 2008 to 2017. Eighty-seven percent of these individuals were found to have either a genetic syndrome or pathogenic or likely pathogenic variant in a cardiac-related gene. None of these individuals had a personal or family history of cardiomyopathy that was suggestive of a genetic aetiology prior to presentation. All of these individuals either passed away or were listed for cardiac transplantation indicating genetic testing may provide important information regarding prognosis in addition to providing information critical to assessment of family members.

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.

Current management and clinical outcomes for catheter ablation of atrioventricular nodal re-entrant tachycardia.

Aims: Historical studies of ablation of atrioventricular nodal re-entrant tachycardia (AVNRT) have shown high long-term success rates and low complication rates. The potential impact of several recent practice trends has not been described. This study aims to characterize recent clinical practice trends in AVNRT ablation and their associated success rates and complications. Methods and results: Patients undergoing initial ablation of AVNRT between 1 July 2005 and 30 June 2015 were included in this study. Patient demographics and procedural data were abstracted from procedure reports. Follow-up data, including AVNRT recurrence and complications, was evaluated through electronic medical record review. In total, 877 patients underwent catheter ablation for AVNRT. By the last recorded year, three-dimension (3D) electroanatomical mapping (EAM) was used in 36.2%, 43.2% included anaesthesia, and 23.1% utilized irrigated catheters. Long-term procedural success was 95.5%. The use of anaesthesia, 3D EAM, and irrigated ablation catheters were not associated with differences in success. The presence of an atrial 'echo' or 'AH' jump at the end of an acutely successful procedure was not associated with long-term recurrence (P = 0.18, P = 0.15, respectively). Complications, including AV block requiring a pacemaker (0.4%), were uncommon. Conclusion: In a large, contemporary cohort, catheter ablation for AVNRT remains highly successful with low complications rates. The increased use of anaesthesia as well as modern mapping and ablation tools were not associated with changes in clinical outcomes. Further prospective evaluation of such contemporary practices is warranted given the lack of evidence to support their escalating use.

Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype.

Rett syndrome (RTT) is caused by MECP2 mutations, resulting in various neurological symptoms. Prolonged corrected QT interval (QTc) is also reported and is a speculated cause of sudden death in RTT. The purpose of this study was to correlate QTc in RTT patients with age, clinical severity, and genotype. 100 RTT patients (98 females, 2 males) with MECP2 mutations underwent baseline neurological evaluation (KKI-RTT Severity Scale) and QTc measurement (standard 12 lead electrocardiogram) as part of our prospective natural history study. Mean QTc of the cohort was 422.6 msec, which did not exceed the normal values for age. 7/100 patients (7%) had QTc prolongation (>450 msec). There was a trend for increasing QTc with age and clinical severity (P = 0.09). No patients with R106C, R106W, R133C, R168*, R270*, R294*, R306C, R306H, and R306P mutations demonstrated QTc prolongation. There was a relatively high proportion of QTc prolongation in patients with R255* mutations (2/8, 25%) and large deletions (1/4, 25%). The overall presence of QTc prolongation did not correlate with mutation category (P = 0.52). Our findings demonstrate that in RTT, the prevalence of QTc prolongation is lower than previously reported. Hence, all RTT patients warrant baseline ECG; if QTc is prolonged, then cardiac followup is warranted. If initial QTc is normal, then annual ECGs, particularly in younger patients, may not be necessary. However, larger sample sizes are needed to solidify the association between QTc and age and clinical severity. The biological and clinical significance of mild QTc prolongation above the normative data remains undetermined.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Arrhythmogenic right ventricular dysplasia/cardiomyopathy is an inherited cardiomyopathy characterised by ventricular arrhythmias and an increased risk of sudden cardiac death. Arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnosis is based on criteria that take into account electrical and structural cardiac abnormalities, as well as mutation analysis. Appropriate pharmacological therapy and the prevention of sudden death with implantable defibrillators are important in the management of these patients. Exercise is considered an important environmental factor for the development and progression of the disease.

Novel and highly lethal NKX2.5 missense mutation in a family with sudden death and ventricular arrhythmia.

To date, several disease-related mutations in NKX2-5, a cardiac-specific homeobox gene, have been documented in patients with a variety of congenital heart diseases (CHDs). The most commonly reported phenotypes are secundum atrial septal defect (ASD) and atrioventricular conduction disease (AVCD). Reports of sudden cardiac death (SCD) have been attributed to progressive conduction disease preventable with pacemaker therapy. A retrospective chart review of individuals from three generations of a family with a novel NKX2-5 mutation associated with CHD, ventricular arrhythmias, and SCD despite pacemaker therapy was conducted. The review documented NKX2-5 Gln181His missense mutation in 11 phenotypically affected members of a single family with a strong family history of SCD, CHD, and AVCD. Before genotyping, four family members died suddenly, two despite pacemaker therapy. The ages at SCD were respectively 23, 29, 44, and 45 years. Observed phenotypic characteristics of genotype-positive patients included ASD, ventricular septal defect, aortic coarctation, tricuspid atresia, supraventricular tachycardia, progressive AVCD, and ventricular tachycardia documented on implantable cardiac defibrillator (ICD) recording. The age at presentation ranged from 5 months to 44 years, and AVCD was seen as early as infancy. Four phenotypically unaffected family members tested negative for the mutation. The findings of this review strongly suggest a new association of this NKX2-5 mutation with SCD from ventricular arrhythmia. This observation has significant implications for the choice of therapy for affected individuals, specifically the use of ICDs, and broadens the observed phenotypic spectrum of NKX2-5 mutations.

Placement of implantable cardioverter-defibrillators in paediatric and congenital heart defect patients: a pipeline for model generation and simulation prediction of optimal configurations.

There is currently no reliable way of predicting the optimal implantable cardioverter-defibrillator (ICD) placement in paediatric and congenital heart defect (CHD) patients. This study aimed to: (1) develop a new image processing pipeline for constructing patient-specific heart-torso models from clinical magnetic resonance images (MRIs); (2) use the pipeline to determine the optimal ICD configuration in a paediatric tricuspid valve atresia patient; (3) establish whether the widely used criterion of shock-induced extracellular potential (Φe) gradients ≥5 V cm(-1) in ≥95% of ventricular volume predicts defibrillation success. A biophysically detailed heart-torso model was generated from patient MRIs. Because transvenous access was impossible, three subcutaneous and three epicardial lead placement sites were identified along with five ICD scan locations. Ventricular fibrillation was induced, and defibrillation shocks were applied from 11 ICD configurations to determine defibrillation thresholds (DFTs). Two configurations with epicardial leads resulted in the lowest DFTs overall and were thus considered optimal. Three configurations shared the lowest DFT among subcutaneous lead ICDs. The Φe gradient criterion was an inadequate predictor of defibrillation success, as defibrillation failed in numerous instances even when 100% of the myocardium experienced such gradients. In conclusion, we have developed a new image processing pipeline and applied it to a CHD patient to construct the first active heart-torso model from clinical MRIs.

Tetralogy of Fallot and aortic root dilation: a long-term outlook.

Dilation of the sinus of Valsalva (SoV) has been increasingly observed after repaired tetralogy of Fallot (TOF). We estimate the prevalence of SoV dilation in adults with repaired TOF and analyze possible factors related to aortic disease. Adults with TOF [n = 109, median age 33.2 years (range 18.1 to 69.5)] evaluated at Johns Hopkins Hospital from 2001 to 2009 were reviewed in an observational retrospective cohort study. Median follow-up was 27.3 (range 0.1-48.8) years. SoV dilation was defined as >95 % confidence interval adjusted for age and body surface area (z-score > 2). The prevalence of SoV dilation was 51 % compared with that of a normal population with a mean z-score of 2.03. Maximal aortic diameters were ≥ 4 cm in 39 % (42 of 109), ≥ 4.5 cm in 21 % (23 of 109), ≥ 5 cm in 8 % (9 of 109), and ≥ 5.5 cm in 2 % (2 of 109). There was no aortic dissection or death due contributable to aortic disease. Aortic valve replacement was performed in 1.8 % and aortic root or ascending aorta (AA) replacement surgery in 2.8 % of patients. By multivariate logistic regression analysis, aortic regurgitation (AR) [odds ratio (OR) = 3.09, p = 0.005], residual ventricular septal defect (VSD) (OR = 4.14, p < 0.02), and TOF with pulmonary atresia (TOF/PA) (OR = 6.75, p = 0.03) were associated with increased odds of dilated aortic root. SoV dilation after TOF repair is common and persists with aging. AR, residual VSD, and TOF/PA are associated with increased odds of dilation. AA evaluation beyond the SoV is important. Indexed values are imperative to avoid bias on the basis of age and body surface area.

Sudden Cardiac Death Prediction in Arrhythmogenic Right Ventricular Cardiomyopathy: A Multinational Collaboration.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with ventricular arrhythmias (VA) and sudden cardiac death (SCD). A model was recently developed to predict incident sustained VA in patients with ARVC. However, since this outcome may overestimate the risk for SCD, we aimed to specifically predict life-threatening VA (LTVA) as a closer surrogate for SCD. METHODS: We assembled a retrospective cohort of definite ARVC cases from 15 centers in North America and Europe. Association of 8 prespecified clinical predictors with LTVA (SCD, aborted SCD, sustained, or implantable cardioverter-defibrillator treated ventricular tachycardia >250 beats per minute) in follow-up was assessed by Cox regression with backward selection. Candidate variables included age, sex, prior sustained VA (≥30s, hemodynamically unstable, or implantable cardioverter-defibrillator treated ventricular tachycardia; or aborted SCD), syncope, 24-hour premature ventricular complexes count, the number of anterior and inferior leads with T-wave inversion, left and right ventricular ejection fraction. The resulting model was internally validated using bootstrapping. RESULTS: A total of 864 patients with definite ARVC (40±16 years; 53% male) were included. Over 5.75 years (interquartile range, 2.77-10.58) of follow-up, 93 (10.8%) patients experienced LTVA including 15 with SCD/aborted SCD (1.7%). Of the 8 prespecified clinical predictors, only 4 (younger age, male sex, premature ventricular complex count, and number of leads with T-wave inversion) were associated with LTVA. Notably, prior sustained VA did not predict subsequent LTVA (P=0.850). A model including only these 4 predictors had an optimism-corrected C-index of 0.74 (95% CI, 0.69-0.80) and calibration slope of 0.95 (95% CI, 0.94-0.98) indicating minimal over-optimism. CONCLUSIONS: LTVA events in patients with ARVC can be predicted by a novel simple prediction model using only 4 clinical predictors. Prior sustained VA and the extent of functional heart disease are not associated with subsequent LTVA events.

Subcutaneous Implantable Cardioverter-Defibrillator in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: A Transatlantic Experience.

Background Despite growing use of the subcutaneous implantable cardioverter-defibrillator (S- ICD ), its clinical role in arrhythmogenic right ventricular cardiomyopathy/dysplasia ( ARVC /D) patients remains undefined. We aim to elucidate the cardiac phenotype, implant characteristics, and long-term efficacy regarding appropriate therapy and complications in ARVC /D patients with an S- ICD implant. Methods and Results A transatlantic cohort of ARVC /D patients who underwent S- ICD implantation was analyzed for clinical characteristics, S- ICD therapy, and long-term outcome including device-related complications. The cohort included 29 patients (52% male, 76% probands, 59% with ARVC /D-associated mutation, 59% primary prevention [no prior sustained ventricular arrhythmias], and 45% first-generation S- ICD devices). At implant, all inducible patients (27/29) had conversion of induced ventricular fibrillation. Two patients (7%) had superficial infections of the incision site that were treated conservatively. Over a median follow-up of 3.16 years (interquartile range: 2.21-4.51 years), all episodes (6 patients, 4% per year) of sustained ventricular arrhythmias were appropriately detected and treated. Six patients (21%) experienced 39 inappropriate shocks, with 3 requiring device explantation. Oversensing of noncardiac signal (n=4; especially myopotentials) and cardiac signal (n=4) was the most frequent etiology. No lead or device dislodgement, infection, skin erosion, or explantation related to need for antitachycardia pacing was noted. Conclusions S- ICD can effectively treat both induced and spontaneous ventricular arrhythmias in patients with ARVC /D. The rate of inappropriate shocks, although considerable, is comparable to that in ARVC /D patients treated with transvenous ICD s. When they occurred, inappropriate shocks were primarily due to cardiac and, uniquely, noncardiac oversensing. We suggest potential strategies for minimizing inappropriate therapy.

Impact of Exercise Restriction on Arrhythmic Risk Among Patients With Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Prior studies have shown a close link between exercise and development of arrhythmogenic right ventricular cardiomyopathy. How much exercise restriction reduces ventricular arrhythmia (VA), how genotype modifies its benefit, and whether it reduces risk sufficiently to defer implantable cardioverter-defibrillator (ICD) placement in arrhythmogenic right ventricular cardiomyopathy are unknown. METHODS AND RESULTS: We interviewed 129 arrhythmogenic right ventricular cardiomyopathy patients (age: 34.0±14.8 years; male: 60%) with ICDs (36% primary prevention) about exercise participation. Exercise change was defined as annual exercise duration and dose in the 3 years before clinical presentation minus that after presentation. The primary outcome was appropriate ICD therapy for VA. During the 5.1 years (interquartile range: 2.7-10.8 years) after presentation, 74% (95/129) patients reduced exercise dose and 85 (66%) patients experienced the primary outcome. In multivariate analyses, top tertile reduction in exercise duration and dose were both associated with less VA (duration: hazard ratio: 0.23 [95% confidence interval, 0.07-0.81]; dose: hazard ratio: 0.14 [95% confidence interval, 0.04-0.44]). Greater reduction in exercise dose conferred greater reduction in VA (P=0.01 for trend). Patients without desmosomal mutations and those with primary-prevention ICDs benefited more from exercise reduction (P=0.16 and P=0.06 for interaction); however, 58% (18/31) of athletes who reduced exercise dose by >80% still experienced VA. CONCLUSIONS: Exercise restriction should be recommended to all arrhythmogenic right ventricular cardiomyopathy patients with ICDs. Patients who are "gene-elusive" and those with primary-prevention devices may particularly benefit. Exercise reduction is unlikely to reduce arrhythmia sufficiently in high-risk patients to alter decision-making regarding ICD implantation.

Frequency of Ventricular Arrhythmias and Other Rhythm Abnormalities in Children and Young Adults With the Marfan Syndrome.

Patients with the Marfan syndrome (MFS) are at risk for sudden death. The contribution of arrhythmias is unclear. This study examines the prevalence of arrhythmias in children with the MFS and their relation to clinical and/or echocardiographic factors. Data from the Pediatric Heart Network randomized trial of atenolol versus losartan in MFS were analyzed (6 months to 25 years old, aortic root diameter z-score > 3.0, no previous aortic surgery and/or dissection). Baseline 24-hour ambulatory electrocardiographic monitoring was performed. Significant ventricular ectopy (VE) and supraventricular ectopy (SVE) were defined as ≥10 VE or SVE/hour, or the presence of high-grade ectopy. Three-year composite clinical outcome of death, aortic dissection, or aortic root replacement was analyzed. There were 274 analyzable monitors on unique patients from 11 centers. Twenty subjects (7%) had significant VE, 13 (5%) significant SVE; of these, 2 (1%) had both. None had sustained ventricular or supraventricular tachycardia. VE was independently associated with increasing number of major Ghent criteria (odds ratio [OR] = 2.13/each additional criterion, p = 0.03) and greater left ventricular end-diastolic dimension z-score (OR = 1.47/each 1 unit increase in z-score, p = 0.01). SVE was independently associated with greater aortic sinotubular junction diameter z-score (OR = 1.56/each 1 unit increase in z-score, p = 0.03). The composite clinical outcome (14 events) was not related to VE or SVE (p ≥ 0.3), but was independently related to heart rate variability (higher triangular index). In conclusion, in this cohort, VE and SVE were rare. VE was related to larger BSA-adjusted left ventricular size. Routine ambulatory electrocardiographic monitoring may be useful for risk stratification in select MFS patients.

Lightning, sudden cardiac death, simulation and an automated external defibrillator: the perfect storm.

This is a report of an 11-year-old boy who had sudden cardiac death after a lightning strike while playing lacrosse at summer camp. The camp staff had performed weekly drills to prepare for various medical emergencies and quickly activated their "Emergency Activation System". The child received immediate cardiopulmonary resuscitation (CPR) and was defibrillated with an automated defibrillator (AED) within 3 min of becoming pulseless and was ultimately resuscitated after being defibrillated three times. A community ambulance with a defibrillator on board did not arrive until several minutes after the on-site team had achieved return of spontaneous circulation. In this report, we describe the clinical course of this patient; briefly review lightning injuries, other causes of sudden cardiac death in children and use of AEDs. Finally, we review how simulation has been used in this case and others as a mechanism to ensure preparedness for medical emergencies. This child is alive and well today because of these well-trained camp counselors. Their system of using simulation to maintain emergency readiness serves as an example for lay and professional medical providers alike.

Implantable Cardioverter-Defibrillator Therapy in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: Predictors of Appropriate Therapy, Outcomes, and Complications.

BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is characterized by ventricular arrhythmias and sudden cardiac death. Once the diagnosis is established, risk stratification to determine whether implantable cardioverter-defibrillator (ICD) placement is warranted is critical. METHODS AND RESULTS: The cohort included 312 patients (163 men, age at presentation 33.6±13.9 years) with definite arrhythmogenic right ventricular dysplasia/cardiomyopathy who received an ICD. Over 8.8±7.33 years, 186 participants (60%) had appropriate ICD therapy and 58 (19%) had an intervention for ventricular fibrillation/flutter. Ventricular tachycardia at presentation (hazard ratio [HR]: 1.86; 95% confidence interval [CI], 1.38-2.49; P<0.001), inducibility on electrophysiology study (HR: 3.14; 95% CI, 1.95-5.05; P<0.001), male sex (HR: 1.62; 95% CI, 1.20-2.19; P=0.001), inverted T waves in ≥3 precordial leads (HR: 1.66; 95% CI, 1.09-2.52; P=0.018), and premature ventricular contraction count ≥1000/24 hours (HR: 2.30; 95% CI, 1.32-4.00; P=0.003) were predictors of any appropriate ICD therapy. Inducibility at electrophysiology study (HR: 2.28; 95% CI, 1.10-4.70; P=0.025) remained as the only predictor after multivariable analysis. The predictors for ventricular fibrillation/flutter were premature ventricular contraction ≥1000/24 hours (HR: 4.39; 95% CI, 1.32-14.61; P=0.016), syncope (HR: 1.85; 95% CI, 1.10-3.11; P=0.021), aged ≤30 years at presentation (HR: 1.76; 95% CI, 1.04-3.00; P<0.036), and male sex (HR: 1.73; 95% CI, 1.01-2.97; P=0.046). Younger age at presentation (HR: 3.14; 95% CI, 1.32-7.48; P=0.010) and high premature ventricular contraction burden (HR: 4.43; 95% CI, 1.35-14.57; P<0.014) remained as independent predictors of ventricular fibrillation/flutter. Complications occurred in 66 participants (21%), and 64 (21%) had inappropriate ICD interventions. Overall mortality was low at 2%, and 4% underwent heart transplantation. CONCLUSION: These findings represent an important step in identifying predictors of ICD therapy for potentially fatal ventricular fibrillation/flutter and should be considered when developing a risk stratification model for arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Recommendations for physical activity and recreational sports participation for young patients with genetic cardiovascular diseases.

A group of relatively uncommon but important genetic cardiovascular diseases (GCVDs) are associated with increased risk for sudden cardiac death during exercise, including hypertrophic cardiomyopathy, long-QT syndrome, Marfan syndrome, and arrhythmogenic right ventricular cardiomyopathy. These conditions, characterized by diverse phenotypic expression and genetic substrates, account for a substantial proportion of unexpected and usually arrhythmia-based fatal events during adolescence and young adulthood. Guidelines are in place governing eligibility and disqualification criteria for competitive athletes with these GCVDs (eg, Bethesda Conference No. 26 and its update as Bethesda Conference No. 36 in 2005). However, similar systematic recommendations for the much larger population of patients with GCVD who are not trained athletes, but nevertheless wish to participate in any of a variety of recreational physical activities and sports, have not been available. The practicing clinician is frequently confronted with the dilemma of designing noncompetitive exercise programs for athletes with GCVD after disqualification from competition, as well as for those patients with such conditions who do not aspire to organized sports. Indeed, many asymptomatic (or mildly symptomatic) patients with GCVD desire a physically active lifestyle with participation in recreational and leisure-time activities to take advantage of the many documented benefits of exercise. However, to date, no reference document has been available for ascertaining which types of physical activity could be regarded as either prudent or inadvisable in these subgroups of patients. Therefore, given this clear and present need, this American Heart Association consensus document was constituted, based largely on the experience and insights of the expert panel, to offer recommendations governing recreational exercise for patients with known GCVDs.

Implantable cardioverter-defibrillators in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy.

OBJECTIVES: The aim of this study was to assess the outcome of arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) patients treated with an implantable cardioverter-defibrillator (ICD). BACKGROUND: Arrhythmogenic right ventricular dysplasia/cardiomyopathy is associated with tachyarrhythmia and an increased risk of sudden death. METHODS: This study included 42 ARVD/C patients with ICDs (52% male, age 6 to 69 years, median 37 years) followed at our center. RESULTS: Mean follow-up was 42 +/- 26 months (range 4 to 135 months). Complications associated with ICD implantation included need for lead repositioning (n = 3) and system infection (n = 2). During follow-up, one patient died of a brain malignancy and one had heart transplantation. Lead replacement was required in six patients as a result of lead fracture and insulation damage (n = 4) or change in thresholds (n = 2). During this period, 33 of 42 (78%) patients received a median of 4 (range 1 to 75) appropriate ICD interventions. The median period between ICD implantation and the first firing was 9 months (range 0.1 to 66 months). The ICD firing storms were observed in five patients. Inappropriate interventions were seen in 10 patients. Predictors of appropriate firing were induction of ventricular tachycardia (VT) during electrophysiologic study (EPS) (84% vs. 44%, p = 0.024), detection of spontaneous VT (70% vs. 15%, p = 0.001), male versus female gender (91% vs. 65%, p = 0.04), and severe right ventricular dilation (39% vs. 0%, p = 0.013). Using multivariate analysis, VT induction during EPS was associated with increased risk for firing in ARVD/C patients; odds ratio 11.2 (95% confidence interval 1.23 to 101.24, p = 0.031). CONCLUSIONS: Patients with ARVD/C have a high arrhythmia rate requiring appropriate ICD interventions. The ICD therapy appears to be well tolerated and important in the management of patients with ARVD/C.

Electrocardiographic findings over time in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Thirty-five patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy underwent serial electrocardiographic (ECG) testing and were evaluated for evidence of ECG progression. Over a median of 43 months, 89% of the patients had evidence of progression, with S-wave prolongation being the most prevalent marker of ECG progression.