Binu Philips

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.

Outcomes of catheter ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Background—Prior studies evaluating the efficacy of catheter ablation of ventricular tachycardia (VT) among patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) have reported varied outcomes. More recently, studies have suggested that an epicardial ablation is necessary for improved outcomes after catheter ablation of VT. The overall objective of the present study was to assess the efficacy of radiofrequency catheter ablation (RFA) of VT in ARVD/C, with particular focus on newer ablation strategies, including epicardial catheter ablation. Methods and Results—The study population included 87 patients with ARVD/C who underwent a total of 175 RFA procedures between 1992 and 2011 at 80 different electrophysiology centers. Recurrence of VT following RFA and effect of RFA on the burden of VT were assessed. The mean age of the cohort was 38 ± 13 years. Over a mean follow-up of 88.3 ± 66 months, the overall freedom from VT of the 175 procedures was 47%, 21%, and 15%, at 1, 5, and 10 years, respectively. The cumulative freedom from VT following epicardial RFA was 64% and 45% at 1 and 5 years, respectively, which was significantly longer than endocardial RFA (P=0.021). Survival free of VT among procedures with 3D electroanatomic mapping was significantly longer compared to those without (P=0.016). Burden of VT was reduced irrespective of the ablation strategy (P<0.001). Conclusions—Although VT recurrences are common, RFA results in a significant reduction in the burden of VT in patients with ARVD/C. Further, although the use of 3D electroanatomic mapping systems and epicardial ablation strategies are associated with longer survival free of VT, recurrence rates remain considerable.

Risk Stratification in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy Associated Desmosomal Mutation Carriers

Background—We investigated the role of phenotypic characteristics in stratifying the risk of sustained ventricular arrhythmias in patients harboring arrhythmogenic right ventricular dysplasia/cardiomyopathy–associated mutations. Methods and Results—Clinical, electrocardiographic, and arrhythmic outcome (composite measure of first occurrence of sustained ventricular tachycardia/resuscitated sudden cardiac death/sudden cardiac death/appropriate implantable cardioverter-defibrillator therapy) data were obtained for 215 patients (104 families; 85% PKP-2). During a mean follow-up of 7 years, 86 (40%) patients experienced the arrhythmic outcome. Event-free survival was significantly lower among probands (P<0.001) and symptomatic (P<0.001) patients. Integration of ECG repolarization and depolarization abnormalities allowed for differential risk categorization. Event-free survival at 5 years for the low-risk ECG group (0–1 T inversions or minor depolarization changes) was 97% versus 81% for the intermediate-risk ECG group (2 T inversions+minor depolarization changes) versus 33% for the high-risk ECG group (≥3 T inversions±major or minor depolarization changes; P<0.001). Incremental arrhythmic risk was seen in patients with increasing premature ventricular complex count on a Holter (P<0.001). Proband status (hazard ratio, 7.7; 95% confidence interval, 2.8–22.5; P<0.001), ≥3 T-wave inversions (hazard ratio, 4.2; 95% confidence interval, 1.2–14.5; P=0.035), and male sex (hazard ratio, 1.8; 95% confidence interval, 1.2–2.8; P=0.004) were independent predictors of the first arrhythmic event on multivariable analysis. Conclusions—Pedigree evaluation, an ECG, and a Holter examination provide for comprehensive arrhythmic risk stratification in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy–associated mutations. We propose an approach to risk stratification based on these variables.

Mutation-Positive Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy: The Triangle of Dysplasia Displaced

The traditional description of the Triangle of Dysplasia in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy (ARVD/C) predates genetic testing and excludes biventricular phenotypes.

Cardiac Transplantation in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is an inherited cardiomyopathy characterized by fibrofatty replacement of the ventricular myocardium, right ventricular (RV) dysfunction, and ventricular arrhythmias. The Johns Hopkins ARVD Program Registry, which was established in

High Prevalence of Catecholamine-facilitated Focal Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Background—Exercise-related ventricular tachycardia (VT) and high burden of premature ventricular contractions (PVCs) are common in arrhythmogenic right ventricular dysplasia/cardiomyopathy. We hypothesized that VT in arrhythmogenic right ventricular dysplasia/cardiomyopathy shows a high degree of association with the PVC at baseline. Methods and Results—The study population included 16 consecutive arrhythmogenic right ventricular dysplasia/cardiomyopathy patients with recurrent VT who underwent catheter ablation. Median age of the patients was 27 years (range, 18–66) and 50% were men. All patients had frequent ectopy at baseline with a median PVC count of 7275 (range, 1353–19 084). During EP study, a total of 27 VTs were induced, of which 16 (59%) occurred during high-dose isoproterenol infusion. VT morphology was identical to the baseline PVCs in all the VTs induced during high-dose isoproterenol infusion. Focal ablation at the site of earliest activation and 12/12 pace map of the PVC eliminated the VT in all cases. Target site for focal ablation localized to scar border. Cumulative freedom from VT after ablation was 85.2% and 74.5% at 1 and 2 years, respectively, which was associated with a reduction in PVC count. Conclusions—We report a high degree of association between PVCs at baseline and the VTs induced during catecholamine infusion. These VTs originated from the border region of scar most commonly in the right ventricular outflow tract and right ventricle basal regions. These findings highlight the importance of catecholamine challenge and PVC mapping, which can in turn facilitate ablation of the VT in arrhythmogenic right ventricular dysplasia/cardiomyopathy.

Outcomes and ventricular tachycardia recurrence characteristics after epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia/cardiomyopathy

BACKGROUND Variable success rates have been reported after epicardial radiofrequency catheter ablation (RFA) in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). The details of the electroanatomic substrate are limited to a few studies, and the characteristics of the recurrent ventricular tachycardia (VT) in ARVD/C remain largely unknown. OBJECTIVE The purpose of this study was to report procedural strategy, safety, and efficacy of epicardial RFA at a tertiary single center with a focus on the characteristics of the substrate and recurrent VT. METHODS We included 30 ARVD/C patients (mean age 33.1 ± 11.1 years, 53% male) who underwent endocardial/epicardial mapping and epicardial catheter ablation of VT at the Johns Hopkins Hospital. Implantable cardioverter-defibrillator interrogations were evaluated for VT recurrence. RESULTS The majority of critical VT circuits (69%) were on the epicardial surface, mostly in the subtricuspid region. Eight patients (27%) experienced VT recurrence after epicardial RFA, and the VT-free survival was 83%, 76%, and 70% at 6,12, and 24, months respectively. A significant reduction of VT burden was observed (P <.001), even among those with VT recurrence. No complications occurred except for acute pericarditis in 1 patient. The majority of VT recurrences occurred during the first year after RFA, during exercise, had fast cycle lengths, and required implantable cardioverter-defibrillator shock for termination. CONCLUSION The vast majority of critical VT circuits were epicardial, mostly in the subtricuspid region. Epicardial RFA of VT appears to be both safe and effective in achieving arrhythmia control in ARVD/C. The features of the recurrent VT suggest a possible catecholamine-mediated mechanism with an origin in a region not targeted for ablation.

Arrhythmogenic Right Ventricular Dysplasia/ Cardiomyopathy and Cardiac Sarcoidosis Distinguishing Features When the Diagnosis Is Unclear

Background— Cardiac sarcoidosis (CS) may show overlap in the clinical presentation with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). We sought to investigate patients with CS who were misdiagnosed with ARVD/C and identify clinical features to distinguish these 2 groups. Methods and Results— Among patients enrolled in the Johns Hopkins ARVD/C registry, 15 patients with definite 2010 diagnostic criteria for ARVD/C were subsequently diagnosed with CS. Forty-two pathogenic desmosomal mutation carriers with definite ARVD/C based on the 2010 diagnostic criteria served as a control group. Patients with CS were older at the age of symptom onset, more likely to have comorbidities, and develop heart failure symptoms over time ( P <0.05). Electrocardiographically, PR interval prolongation and high-grade atrioventricular block were exclusively associated with CS ( P <0.05). HV interval prolongation and increased number of ventricular tachycardias induced were also associated with CS ( P <0.05). Radiographically, significant left ventricular dysfunction, myocardial delayed enhancement of the septum, and mediastinal lymphadenopathy were more often see in those with CS ( P <0.05). Conclusions— The 2010 diagnostic criteria for ARVD/C have limited discrimination in distinguishing between ARVD/C and CS. Despite the overlay in clinical presentation, older age of symptom onset, presence of cardiovascular comorbidities, nonfamilial pattern of disease, PR interval prolongation, high-grade atrioventricular block, significant left ventricular dysfunction, myocardial delayed enhancement of the septum, and mediastinal lymphadenopathy should raise the suspicion for CS.Background—Cardiac sarcoidosis (CS) may show overlap in the clinical presentation with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). We sought to investigate patients with CS who were misdiagnosed with ARVD/C and identify clinical features to distinguish these 2 groups. Methods and Results—Among patients enrolled in the Johns Hopkins ARVD/C registry, 15 patients with definite 2010 diagnostic criteria for ARVD/C were subsequently diagnosed with CS. Forty-two pathogenic desmosomal mutation carriers with definite ARVD/C based on the 2010 diagnostic criteria served as a control group. Patients with CS were older at the age of symptom onset, more likely to have comorbidities, and develop heart failure symptoms over time (P<0.05). Electrocardiographically, PR interval prolongation and high-grade atrioventricular block were exclusively associated with CS (P<0.05). HV interval prolongation and increased number of ventricular tachycardias induced were also associated with CS (P<0.05). Radiographically, significant left ventricular dysfunction, myocardial delayed enhancement of the septum, and mediastinal lymphadenopathy were more often see in those with CS (P<0.05). Conclusions—The 2010 diagnostic criteria for ARVD/C have limited discrimination in distinguishing between ARVD/C and CS. Despite the overlay in clinical presentation, older age of symptom onset, presence of cardiovascular comorbidities, nonfamilial pattern of disease, PR interval prolongation, high-grade atrioventricular block, significant left ventricular dysfunction, myocardial delayed enhancement of the septum, and mediastinal lymphadenopathy should raise the suspicion for CS.

Phrenic Nerve Injury: An Underrecognized and Potentially Preventable Complication of Pulmonary Vein Isolation Using a Wide-Area Circumferential Ablation Approach

Phrenic nerve injury (PNI) is a well‐known, although uncommon, complication of pulmonary vein isolation (PVI) using radiofrequency energy. Currently, there is no consensus about how to avoid or minimize this injury. The purpose of this study was to determine how often the phrenic nerve, as identified using a high‐output pacing, lies along the ablation trajectory of a wide‐area circumferential lesion set. We also sought to determine if PVI can be achieved without phrenic nerve injury by modifying the ablation lesion set so as to avoid those areas where phrenic nerve capture (PNC) is observed.

Electroanatomic Correlates of Depolarization Abnormalities in Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy.

Epsilon waves and other depolarization abnormalities in the right precordial leads are thought to represent delayed activation of the right ventricular outflow tract in arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). However, no study has directly correlated cardiac electrical activation with the surface ECG findings in ARVD/C.