Ventricular tachycardia ablation in arrhythmogenic right ventricular cardiomyopathy patients with TMEM43 gene mutations

1 Introduction

Catheter ablation of VT in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) is often challenging, frequently requiring multiple or epicardial ablation procedures; TMEM43 gene mutations typically cause aggressive disease. We sought to compare VT ablation outcomes for ARVC patients with and without TMEM43 mutations.

2 Methods

Patients with prior ablation for ARVC‐related VT were reviewed. Demographic, procedural, and follow‐up data were reviewed retrospectively. Patients with confirmed TMEM43 gene mutations were compared to those with other known mutations or who had no known mutations.

3 Results

Thirteen patients (10 male, mean age 49 ± 14 years) underwent 29 ablation procedures (median 2 procedures/patient, range 1–6) with a median of 4 targeted VTs/patient (range 1–9). They were followed for a mean duration of 7.3 ± 4.2 years. Gene mutations included TMEM43 (n = 5), PKP2 (n = 2), DSG2 (n = 2), unidentifiable (n = 4). TMEM patients showed more biventricular involvement compared to non‐TMEM patients (80% vs. 12.5%, P = 0.032), more inducible VTs during their ablation procedures (mean VTs/patient: 5.8 ± 3 vs. 2.6 ± 1, P = 0.021). Acute and long‐term procedural outcomes did not show a significant difference between the two groups, however TMEM patients had worse composite endpoint of death or transplantation (60% vs. 0, P = 0.035; log‐rank P = 0.013).

4 Conclusions

TMEM43 mutation patients were more likely to have biventricular arrhythmogenic substrate and more inducible VTs at EP study. Despite comparable acute VT ablation outcomes, long‐term prognosis is unfavorable.     

Contrast echocardiography for perfusion in right ventricular cardiomyopathy.

Right ventricular (RV) cardiomyopathy is a familiar myocardial disease of RV characterized by extensive fatty replacement of the myocardium. Conventional echocardiography is able to show abnormalities in myocardial contractility, but fat on the images appears to be similar to the surrounding tissue or fluid. The present case suggests the clinical role of contrast echocardiography showing perfusion abnormalities in patients with RV cardiomyopathy in the region of the fat depositions.     

Arrhythmogenic right ventricular dysplasia presenting as right ventricular outflow tract tachycardia.

A case of a 51-year old male is presented. A left bundle branch block inferior axis tachycardia was manifest. At electrophysiological study this tachycardia was inducible and was ablated in the septal right ventricular outflow tract (RVOT). Two other tachycardias were identified both with right bundle branch block (RBBB) morphology raising the suspicion of diffuse pathology. Arrythmogenic right ventricular dysplasia (ARVD) was confirmed by right ventricular angiography and magnetic resonance imaging (MRI). An implantable cardioverter defibrillator (ICD) was implanted and an appropriate shock was later delivered.     

Arrhythmogenic Right Ventricular Cardiomyopathy 2012: Diagnostic Challenges and Treatment

ARVC 2012 . The most common presentation of arrhythmogenic right ventricular cardiomyopathy (ARVC) is palpitations or ventricular tachycardia (VT) of left bundle branch morphology in a young or middle‐aged individual. The 12‐lead electrocardiogram may be normal or have T‐wave inversion beyond V₁ in an otherwise healthy person who is suspected of having ARVC. The most frequent imaging abnormalities are an enlarged right ventricle, decrease in right ventricular (RV) function, and localized wall motion abnormalities. Risk factors for implantable cardioverter defibrillator include a history of aborted sudden death, syncope, young age, decreased left ventricular function, and marked decrease in RV function. Recent results of treatment with epicardial ablation are encouraging. (J Cardiovasc Electrophysiol, Vol. 23 pp. 1149‐1153, October 2012)     

Long-term follow-up in patients with arrhythmogenic right ventricular cardiomyopathy

Long‐Term Prognosis in Patients with ARVC. Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a major cause of sudden cardiac death due to tachyarrhythmias. The purpose of this study was to investigate the long‐term prognosis in patients with ARVC and the incidence of rapid ventricular arrhythmias during follow‐up. Methods: Thirty ARVC patients (19 male, 63.3%, mean age 48 ± 15 years) fulfilling modified Task Force criteria 2010 were included. Of them, 13 patients (43.3%) received implantable cardioverter‐defibrillator (ICD) implantation. Rapid ventricular arrhythmia was defined as electrical storm or the occurrence of ventricular tachycardia (VT) or ventricular fibrillation (VF) with a cycle length of 240 ms or less that necessitate shock delivery to 2 or more times within a 24‐hour period. Results: With a mean follow‐up of 68 ± 10 months, 6 patients (20%) with ICD implantation had recurrent rapid VT/VF. One (3.3%) of them died of multiple shocks and SCD, and 5 (16.7%) had multiple ICD therapies due to VT/VF and electrical storm. The interval between the diagnosis of ARVC and occurrence of rapid VT/VF was 13.4 ± 4.9 months. Most (5/6, 83.3%) events of recurrent rapid VT/VF occurred within 2 years. Ablated patients who did not receive an ICD implant were totally free of rapid VT/VF. Conclusions: For patients with ARVC, long‐term prognosis is favorable. During a long‐term follow‐up, patients meeting the criteria for ICD implantation have a higher rate of rapid and potentially life‐threatening arrhythmias. However, early and clustered recurrence of rapid VT/VF in patients with an ICD is common, whereas late occurrence of rapid VT/VF is very rare. (J Cardiovasc Electrophysiol, Vol. 23, pp. 750‐756, July 2012)     

Newly diagnosed arrhythmogenic right ventricular dysplasia in an octogenarian

Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is thought to be a disease of the young, with the majority of newly diagnosed patients under 40 years of age. Establishing this diagnosis in elderly patients may be challenging, and a few reports exist of patients older than 70 years diagnosed with ARVD/C at autopsy. We report the case of an octogenarian with antemortem newly diagnosed ARVD/C. This case report represents the oldest patient to date to have a newly established diagnosis of ARVD/C and highlights the difficulty in making the diagnosis in the elderly.     

Long term results of cardioverter-defibrillator implantation in patients with right ventricular dysplasia and malignant ventricular tachyarrhythmias

OBJECTIVE—To study the outcome of patients with arrhythmogenic right ventricular dysplasia treated with an implantable cardioverter-defibrillator (ICD) for ventricular tachyarrhythmias complicated by haemodynamic collapse.
DESIGN—Observational study.
SETTING—University hospital.
PATIENTS—Nine consecutive patients (eight male, one female; mean (SD) age, 36 (18) years) with arrhythmogenic right ventricular dysplasia presenting with ventricular tachycardia and haemodynamic collapse (n = 6) or ventricular fibrillation (n = 3), treated with an ICD.
MAIN OUTCOME MEASURES—Survival; numbers of and reasons for appropriate and inappropriate ICD interventions.
RESULTS—After a mean (SD) follow up of 32 (24) months, all patients were alive. Six patients received a median of 19 (range 2-306) appropriate ICD interventions for events detected in the ventricular tachycardia window; four received a median of 2 (range 1-19) appropriate ICD interventions for events detected in the ventricular fibrillation window. Inappropriate interventions were seen for sinus tachycardia (18 episodes in three patients), atrial fibrillation (three episodes in one patient), and for non-sustained polymorphic ventricular tachycardia (one episode in one patient).
CONCLUSIONS—Patients with arrhythmogenic right ventricular dysplasia and malignant ventricular arrhythmias have a high recurrence rate requiring appropriate ICD interventions, but they also often have inappropriate interventions. Programming the device is difficult because this population develops supraventricular and ventricular tachyarrhythmias with similar rates.


Keywords: arrhythmogenic right ventricular dysplasia; implantable cardioverter defibrillator; arrhythmia     

Arrhythmogenic Right Ventricular Dysplasia: Clinical Results with Implantable Cardioverter Defibrillators

Arrhythmogenic right ventricular dysplasia is a clinical entitycharacterized by fatty infiltration of the right ventricle and left bundlemorphology ventricular tachycardia occurring in young patients. The mostcommon cause of death is tachyarrhythmic. Pharmacological andnonpharmacological therapies, including implantable cardioverterdefibrillators, have been used to treat the arrhythmias. However, rightventricular endocardial leads in this population may be associated with anincreased risk of perforation and suboptimal sensing and defibrillationefficacy due to the diseased right ventricle. We report on 12 patients witharrhythmogenic right ventricular dysplasia who were treated with implantablecardioverter defibrillators. The mean age was 31± 9 years (range15-48). Patients presented with presyncope (5), syncope (4), or cardiacarrest (3). All patients had electrocardiographic abnormalitiescharacteristic of the condition.Follow-up averaged 22 ± 13months (range 1-45). There was one sudden death at 1 month of follow-up. Ofthe 12 patients, 8 have had appropriate therapy delivered by the implantabledefibrillator. Six patients are currently on sotalol to reduce the frequencyof implantable defibrillator discharges. In conclusion, implantablecardioverter defibrillators with nonthoracotomy leads are feasible and safein patients with arrhythmogenic right ventricular dysplasia. The frequencyof appropriate therapy is high, supporting the use of implantablecardioverter defibrillators in this population.During programmedelectrical stimulation nine patients had sustained ventricular tachycardia,while three patients had no inducible arrhythmia. Transvenous leads wereplaced in nine patients. In these patients pacing thresholds weresignificantly higher, R-wave amplitudes were significantly lower, anddefibrillation thresholds were not significantly different than in a cohortof patients without right ventricular dysplasia. There were no acute orchronic complications of right ventricular lead placement.     

Incidence of nonsustained and sustained ventricular tachyarrhythmias in patients with an implantable cardioverter defibrillator

INTRODUCTION: Nonsustained ventricular tachycardia (NSVT) is a frequent phenomenon in some patients with heart disease, but its association with sustained ventricular tachycardias (ventricular tachycardia [VT]/ventricular fibrillation [VF]) is still not clear. The aim of this study was to determine whether NSVT incidence was associated with sustained VT/VF in patients with an implantable cardioverter defibrillator (ICD). METHODS AND RESULTS: Retrospective data analysis was conducted in 923 ICD patients with a mean follow-up of 4 months. NSVT and sustained VT/VF were defined as device-detected tachycardias. The incidence rates of NSVT and sustained VT/VF as well as ICD therapies were determined as episodes per patient. The NSVT index was defined as the product of NSVT episodes/day times the mean number of beats per episode, i.e., total beats/day. The NSVT index peak was defined as the highest value on or prior to the day with sustained VT/VF episodes. Patients (n = 393) with NSVT experienced a higher incidence of sustained VT/VF (17.2 +/- 63.0 episodes/patient) and ICD therapies (15.2 +/- 61.4 episodes/patient) than patients (n = 530) without NSVT (sustained VT/VF: 0.5 +/- 6.6 and therapies: 0.5 +/- 5.6; P < 0.0001). Approximately 74% of NSVT index peaks occurred on the same day or <3 days prior to sustained VT/VF episodes. The index was higher for peaks < or =3 days prior to the day with sustained VT/VF (94.3 +/- 140.1 total beats/day) than for peaks >3 days prior to the day with sustained VT/VF (32.7 +/- 55.9 total beats/day; P < 0.0001). CONCLUSION: ICD patients with NSVT represent a population more likely to experience sustained VT/VF episodes with a temporal association between an NSVT surge and sustained VT/VF occurrence.     

Arrhythmogenic ventricular cardiomyopathy:A paradigm shift from right to biventricular disease

Arrhythmogenic ventricular cardiomyopathy(AVC) isgenerally referred to as arrhythmogenic right ventricu-lar(RV) cardiomyopathy/dysplasia and constitutesan inherited cardiomyopathy.Affected patients maysuccumb to sudden cardiac death(SCD),ventriculartachyarrhythmias(VTA) and heart failure.Geneticstudies have identified causative mutations in genesencoding proteins of the intercalated disk that lead toreduced myocardial electro-mechanical stability.Theterm arrhythmogenic RV cardiomyopathy is somewhatmisleading as biventricular involvement or isolated leftventricular(LV) involvement may be present and thus abroader term such as AVC should be preferred.The di-agnosis is established on a point score basis accordingto the revised 2010 task force criteria utilizing imagingmodalities,demonstrating fibrous replacement throughbiopsy,electrocardiographic abnormalities,ventricu-lar arrhythmias and a positive family history includingidentification of genetic mutations.Although severarisk factors for SCD such as previous cardiac arrest,syncope,documented VTA,severe RV/LV dysfunctionand young age at manifestation have been identified,risk stratification still needs improvement,especially inasymptomatic family members.Particularly,the roleof genetic testing and environmental factors has to befurther elucidated.Therapeutic interventions include re-striction from physical exercise,beta-blockers,sotalol,amiodarone,implantable cardioverter-defibrillators andcatheter ablation.Life-long follow-up is warranted insymptomatic patients,but also asymptomatic carriersof pathogenic mutations.