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Prof. Josep Brugada
Dr. Juan Fernández-Armenta
We present an update on Arrhythmogenic right ventricular dyplasia (ARVD), presentation, differential diagnosis, management according to risk along with when to recommend an ICD, pharmacological treatment, and our successful experience with first-line use of new techniques in epicardial substrate catheter ablation. Indeed, combined with endocardial substrate guided catheter ablation may be recommended to patients unresponsive or intolerant to antiarrhythmic drugs, and to avoid potential drug side effects.
Arrhythmogenic right ventricular dysplasia (ARVD) is a genetically determined myocardial disease characterised by fibrous fatty replacement and ventricular arrhythmias, involving the right ventricle predominantly, starting at the epicardium and extending transmurally.(1) It usually shows an autosomal dominant pattern i.e possession of this non-sex gene places one at risk for having this disease and offspring of an affected parent will have a 50% chance of inheriting this disease. It has, however incomplete penetrance – i.e it can express itself or not, and furthermore, ARVD has variable expressivity, with genes expressing themselves to varying degrees. (2) Causative mutations in gene encoding desmosomal proteins (plakoglobin, desmoplakin)- i.e proteins that bind cells to one another, are found in approximately half of all ARVD patients. (2, 3) Left ventricular involvement becomes present in a majority of cases and a left dominant form has also been described. (4, 5) Clinical presentations in patients with ARVD vary widely. Heart failure, ventricular arrhythmias and sudden cardiac death (SCD) are the most severe clinical manifestations of ARVD. Early diagnosis appears crucial in preventing SCD. Furthermore, mortality in patients with diagnosed ARVD and an implantable cardioverter defibrillator (ICD) is relatively low. (6) Diagnosing ARVD is nevertheless difficult and is currently based on the presence of major and minor Task Force criteria, which include electrocardiographic, structural (cardiac imaging and histology), clinical and familiar factors. (7) Beyond a personal and family medical history, routine assessment includes electrocardiography, echocardiography, 24-hour Holter monitoring, stress testing, and cardiac magnetic resonance. In uncertain diagnoses, endocardial voltage mapping may help detect the presence of myocardial scar in the disease's early phases (figure 1). Figure 1: Differential diagnosis between idiopathic right ventricular (RV) outflow tract tachycardia and ARVD/C. Panel A: 12-lead electrocardiogram (left) in a patient with no structural heart disease and sustained VT and endocardial voltage mapping (right). Entire RV endocardium shows normal voltage (purple indicates>1.5 mV). Red dots located below the origin of the pulmonary artery (PA) indicate radiofrequency applications. Panel B: Endocardial voltage mapping of a patient diagnosed with ARVD/C showing a subtricuspid lateral low voltage area (red indicates <0.5 mV). The QRS morphology of the VT suggests that the exit of the reentry circuit is located on the RV lateral wall. TA, tricuspid annulus Therapeutic armamentarium for treating ARVD includes antiarrhythmic drugs, the placement of an ICD, radiofrequency ablation and cardiac transplantation. The most important decision in the management of a patient with ARVD is whether to recommend an ICD for treatment of VA and prevention of SCD. Treating patients with an ICD in repeated VA is often difficult; Moreover, antiarrhythmic drugs are frequently ineffective. Although radiofrequency ablation has been relegated as a last therapeutic option, the development of epicardial mapping techniques and substrate-guided ablation have offered promising results.
Although data on risk stratification and management of ARVD is lacking, broad agreement exists that ICD implantation is recommended in patients with documented sustained VA due to high incidence of arrhythmia recurrences. (8, 9) Implantable cardioverter-defibrillator therapy occurs in approximately 10% of ARVD cases per year, and estimated survival benefit is around 25-30% at 3-years follow-up. (9) On the other hand, there is no clear consensus regarding primary prevention of SCD in ARVD patients without documented sustained VA. Several risk markers have been identified, from retrospective studies mostly, as ones of adverse prognosis: syncope, proband status, young age, sporting activity, familial history of SCD, QRS and QT dispersion, severe right ventricular dysfunction, left ventricular involvement or inducible VT. (9-11) ICD implantation is also reasonable in patients with a history of undiagnosed syncope. (8) A cohort of patients with ARVD from a recent multicenter observational study received an ICD for primary prevention based on 1 or more arrhythmic risk factors: syncope, nonsustained ventricular tachycardia, familial SCD, and VA inducibility. Study showed that syncope was an important predictor that ICD therapy will be life-saving. (12) In another recent study involving ICD recipients without prior sustained VA, proband status, presence of nonsustained ventricular tachycardia and inducibility at electrophysiologic study were identified as predictors that ICD therapy is appropriate. (13) The predictive value of programmed ventricular stimulation has shown conflicting results in various studies in the literature and an uncertain role in risk stratification. (1, 12-14) Patients with extensive disease, including left ventricular involvement should be considered for primary prevention of SCD. (8) Sporting activity has been related to increased risk of SCD in patients with ARVD. Furthermore, the overload resulting from training can accelerate the progression of the disease. (15) Indeed, since ARVD is a disease of desmosomal dysfunction, circumstances that increase myocardial strain worsen the mechanical coupling between cardiac myocytes and promote myocardial replacement fibrosis. Indeed, when placed under mechanical stress (exercise) the defective desmosomes, detach from each other, leading to cell death. This cell death causes inflammation with scar formation and fat deposition. Therefore, patients with ARVD - asymptomatic mutation carriers included, should avoid strenuous physical exercise. Competitive sports are altogether contraindicated and recommendations on recreational sport are very restrictive. (16) Recommendations for risk stratification and clinical management are summarised in Table 1. Table 1. Proposed recommendations for clinical management and prevention of sudden cardiac death in patients with ARVD
ARVD: Arrhythmogenic right ventricular dysplasia; CMR: Cardiac magnetic resonance; LF: left ventricle; RV: right ventricle; SCD: Sudden cardiac death; VT: ventricular tachycardia
No clinical trial has studied the efficacy of antiarrhythmic drugs in the treatment of ventricular arrhythmias in patients with ARVD. Other data available however, suggest that β-blockers, sotalol and amiodarone are effective to this end.(17) Antiarrhythmic drugs are useful in ICD recipients with sustained ventricular tachycardia and patients with nonsustained or frequent premature ventricular complexes. The impact of medical therapy on mortality however is not established and in patients with documented sustained VA, medical therapy can only be considered a substitute for an ICD in cases where device implantation is not feasible. As demonstrated in other clinical settings, the role of antiarrhythmic drugs in preventing SCD is probably very limited. Its use should be directed to the prevention of ventricular arrhythmias and their appropriate ICD therapies.(18) Current practice in selection of antiarrhythmic therapy is mostly drawn from a study that compared the efficacy of different drugs based on suppression of ventricular tachycardia in programmed ventricular stimulation.(17, 19) In a recent prospective observational study involving ARVD patients with ICD, in contrast to amiodarone neither β-blockers nor sotalol seemed to be protective against VA. (20) The doses of sotalol administered however (mean 240 mg/day) in this study were lower than those described in studies with positive results (320-480 mg/day). Moreover, side effects of prolonged therapy with amiodarone should be carefully considered, especially in young patients.
Radiofrequency catheter ablation is an option for the treatment of VA in patients with ARVD. This therapeutic option has often been restricted to patients with refractory ventricular tachycardia (11), as a last resort therapy due to limited experience, variable acute and chronic success rates and fear of complications, especially cardiac perforation. However, with the development of new ablation techniques and recent results, we think that catheter ablation can be offered to patients unresponsive or intolerant to antiarrhythmic drugs, and also to avoid the potential occurrence of drug side effects. Catheter ablation can be directed to the clinical or induced ventricular tachycardia. Mapping and ablation techniques are comparable to those used in patients with remote myocardial infarction. (21) The presence of multiple circuits, hemodynamic instability or non-inducibility nevertheless limits this ablation approach. More recently, following the emergence of electroanatomical navigation systems, techniques for the characterisation of the arrhythmia substrate have been developed. Substrate-based mapping and ablation aim to identify and abolish areas that are likely to support reentrant circuits during sinus rhythm. (22) Substrate guided ablation eliminates multiple potential circuits that could result in ventricular tachycardia, regardless of the fact that the arrhythmia may not have been clinically documented or induced during electrophysiological study. Complex arrhythmia substrate of ARVD can justify the better results observed in substrate-guided ablation. (23, 24) Epicardial mapping and ablation have been used in patients with ARVD. (25) Epicardial scar is wider than the endocardial scar in ARVD patients with sustained VA, and the majority of potential isthmuses for ventricular tachycardia are identified on the epicardial surface (Figure 2). Figure 2: Endocardial (ENDO) and epicardial (EPI) voltage maps of a patient submitted for ventricular tachycardia ablation and definite diagnosis of ARVD. Patchy non-confluent scars (< 0.5 mV, in red) are identified at subtricuspid, free wall and outflow levels in the endocardial mapping. An extensive low-voltage area is present in the epicardial surface. The epicardial scar is wider than the endocardial, with higher density of isolated potentials (blue dots). Normal myocardium (>1.5mV) is coded in purple. Red dots: radiofrequency applications.(26) In our experience, a first-line combined endocardial and epicardial substrate guided catheter ablation resulted in a very good short- and mid-term success rate. The high recurrence rate published in earlier series has been attributed to the progressive nature of the disease. However, the known epicardial nature of ARVD should play a key role in the results of conventional endocardial approach. Despite the extensive and complex arrhythmogenic substrate and concerns about cardiac perforation, no study using radiofrequency has reported severe complications from catheter ablation in ARVD patients. The procedure appears to be safe, - in high volume centers at least.
1.Arrhythmogenic right ventricular cardiomyopathy. Basso C, Corrado D, Marcus FI, Nava A, Thiene G.; The Lancet. 2009;373:1289-1300 2.Arrhythmogenic right ventricular dysplasia/cardiomyopathy: Pathogenic desmosome mutations in index-patients predict outcome of family screening: Dutch arrhythmogenic right ventricular dysplasia/cardiomyopathy genotype-phenotype follow-up study. Cox MG, van der Zwaag PA, van der Werf C, van der Smagt JJ, Noorman M, Bhuiyan ZA, Wiesfeld AC, Volders PG, van Langen IM, Atsma DE, Dooijes D, van den Wijngaard A, Houweling AC, Jongbloed JD, Jordaens L, Cramer MJ, Doevendans PA, de Bakker JM, Wilde AA, van Tintelen JP, Hauer RN.; Circulation. 2011;123:2690-2700 3.Desmosomal gene analysis in arrhythmogenic right ventricular dysplasia/cardiomyopathy: Spectrum of mutations and clinical impact in practice. Fressart V, Duthoit G, Donal E, Probst V, Deharo JC, Chevalier P, Klug D, Dubourg O, Delacretaz E, Cosnay P, Scanu P, Extramiana F, Keller D, Hidden-Lucet F, Simon F, Bessirard V, Roux-Buisson N, Hebert JL, Azarine A, Casset-Senon D, Rouzet F, Lecarpentier Y, Fontaine G, Coirault C, Frank R, Hainque B, Charron P.; Europace. 2010;12:861-868 4.Arrhythmogenic right ventricular cardiomyopathy: An update. Thiene G, Basso C.; Cardiovascular pathology: the official journal of the Society for Cardiovascular Pathology. 2001;10:109-117 5.Left-dominant arrhythmogenic cardiomyopathy: An under-recognized clinical entity. Sen-Chowdhry S, Syrris P, Prasad SK, Hughes SE, Merrifield R, Ward D, Pennell DJ, McKenna WJ.; J Am Coll Cardiol. 2008;52:2175-2187 6.Arrhythmogenic right ventricular dysplasia: A United states experience. Dalal D, Nasir K, Bomma C, Prakasa K, Tandri H, Piccini J, Roguin A, Tichnell C, James C, Russell SD, Judge DP, Abraham T, Spevak PJ, Bluemke DA, Calkins H.; Circulation. 2005;112:3823-3832 7.Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: Proposed modification of the task force criteria. Marcus FI, McKenna WJ, Sherrill D, Basso C, Bauce B, Bluemke DA, Calkins H, Corrado D, Cox MGPJ, Daubert JP, Fontaine G, Gear K, Hauer R, Nava A, Picard MH, Protonotarios N, Saffitz JE, Sanborn DMY, Steinberg JS, Tandri H, Thiene G, Towbin JA, Tsatsopoulou A, Wichter T, Zareba W.; Circulation. 2010;121:1533-1541 8.Acc/aha/esc 2006 guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: A report of the american college of cardiology/american heart association task force and the european society of cardiology committee for practice guidelines (writing committee to develop guidelines for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death): Developed in collaboration with the european heart rhythm association and the heart rhythm society. Zipes DP, Camm AJ, Borggrefe M, Buxton AE, Chaitman B, Fromer M, Gregoratos G, Klein G, Moss AJ, Myerburg RJ, Priori SG, Quinones MA, Roden DM, Silka MJ, Tracy C, Smith SC, Jr., Jacobs AK, Adams CD, Antman EM, Anderson JL, Hunt SA, Halperin JL, Nishimura R, Ornato JP, Page RL, Riegel B, Blanc JJ, Budaj A, Dean V, Deckers JW, Despres C, Dickstein K, Lekakis J, McGregor K, Metra M, Morais J, Osterspey A, Tamargo JL, Zamorano JL.; Circulation. 2006;114:e385-484 9.Implantable cardioverter-defibrillator therapy for prevention of sudden death in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia. Corrado D, Leoni L, Link MS, Della Bella P, Gaita F, Curnis A, Salerno JU, Igidbashian D, Raviele A, Disertori M, Zanotto G, Verlato R, Vergara G, Delise P, Turrini P, Basso C, Naccarella F, Maddalena F, Estes NA, 3rd, Buja G, Thiene G.; Circulation. 2003;108:3084-3091 10.Dispersion of ventricular depolarization-repolarization : A noninvasive marker for risk stratification in arrhythmogenic right ventricular cardiomyopathy. Turrini P, Corrado D, Basso C, Nava A, Bauce B, Thiene G.; Circulation. 2001;103:3075-3080 11.Ablation of ventricular arrhythmias in arrhythmogenic right ventricular dysplasia. Arbelo E, Josephson ME.; Journal of Cardiovascular Electrophysiology. 2010;21:473-486 12.Prophylactic implantable defibrillator in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia and no prior ventricular fibrillation or sustained ventricular tachycardia. Corrado D, Calkins H, Link MS, Leoni L, Favale S, Bevilacqua M, Basso C, Ward D, Boriani G, Ricci R, Piccini JP, Dalal D, Santini M, Buja G, Iliceto S, Estes NA, 3rd, Wichter T, McKenna WJ, Thiene G, Marcus FI.; Circulation. 2010;122:1144-1152 13.Incidence and predictors of implantable cardioverter-defibrillator therapy in patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy undergoing implantable cardioverter-defibrillator implantation for primary prevention. Bhonsale A, James CA, Tichnell C, Murray B, Gagarin D, Philips B, Dalal D, Tedford R, Russell SD, Abraham T, Tandri H, Judge DP, Calkins H.; J Am Coll Cardiol. 2011;58:1485-1496 14.Implantable cardioverter/defibrillator therapy in arrhythmogenic right ventricular cardiomyopathy: Single-center experience of long-term follow-up and complications in 60 patients. Wichter T, Paul M, Wollmann C, Acil T, Gerdes P, Ashraf O, Tjan TD, Soeparwata R, Block M, Borggrefe M, Scheld HH, Breithardt G, Bocker D.; Circulation. 2004;109:1503-1508 15.Age- and training-dependent development of arrhythmogenic right ventricular cardiomyopathy in heterozygous plakoglobin-deficient mice. Kirchhof P, Fabritz L, Zwiener M, Witt H, Schafers M, Zellerhoff S, Paul M, Athai T, Hiller KH, Baba HA, Breithardt G, Ruiz P, Wichter T, Levkau B.; Circulation. 2006;114:1799-1806 16.Recommendations for participation in competitive sport and leisure-time physical activity in individuals with cardiomyopathies, myocarditis and pericarditis. Pelliccia A, Corrado D, Bjornstad HH, Panhuyzen-Goedkoop N, Urhausen A, Carre F, Anastasakis A, Vanhees L, Arbustini E, Priori S.; European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology. 2006;13:876-885 17.Efficacy of antiarrhythmic drugs in patients with arrhythmogenic right ventricular disease. Results in patients with inducible and noninducible ventricular tachycardia. Wichter T, Borggrefe M, Haverkamp W, Chen X, Breithardt G.; Circulation. 1992;86:29-37 18.Empiric antiarrhythmic drug therapy in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia: Pragmatism or anachronism? Mitchell LB.; J Am Coll Cardiol. 2009;54:616-617 19.Arrhythmogenic right ventricular cardiomyopathy. Antiarrhythmic drugs, catheter ablation, or icd? Wichter T, Paul TM, Eckardt L, Gerdes P, Kirchhof P, Bocker D, Breithardt G.; Herz. 2005;30:91-101 20.Efficacy of antiarrhythmic drugs in arrhythmogenic right ventricular cardiomyopathy: A report from the north american arvc registry. Marcus GM, Glidden DV, Polonsky B, Zareba W, Smith LM, Cannom DS, Estes NA, 3rd, Marcus F, Scheinman MM.; J Am Coll Cardiol. 2009;54:609-615 21.Catheter ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia. Arruda M, Armaganijan L, Fahmy T, Di Biase L, Patel D, Natale A.; J Interv Card Electrophysiol. 2009;25:129-133 22.Ehra/hrs expert consensus on catheter ablation of ventricular arrhythmias. Aliot EM, Stevenson WG, Almendral-Garrote JM, Bogun F, Calkins CH, Delacretaz E, Bella PD, Hindricks G, JaÃ¯s P, Josephson ME, Kautzner J, Kay GN, Kuck K-H, Lerman BB, Marchlinski F, Reddy V, Schalij M-J, Schilling R, Soejima K, Wilber D.; Europace. 2009;11:771-817 23. Electroanatomic substrate and outcome of catheter ablative therapy for ventricular tachycardia in setting of right ventricular cardiomyopathy. Marchlinski FE, Zado E, Dixit S, Gerstenfeld E, Callans DJ, Hsia H, Lin D, Nayak H, Russo A, Pulliam W.; Circulation. 2004;110:2293-2298 24.Short- and long-term success of substrate-based mapping and ablation of ventricular tachycardia in arrhythmogenic right ventricular dysplasia. Verma A, Kilicaslan F, Schweikert RA, Tomassoni G, Rossillo A, Marrouche NF, Ozduran V, Wazni OM, Elayi SC, Saenz LC, Minor S, Cummings JE, Burkhardt JD, Hao S, Beheiry S, Tchou PJ, Natale A.; Circulation. 2005;111:3209-3216 25.Epicardial substrate and outcome with epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular cardiomyopathy/dysplasia. Garcia FC, Bazan V, Zado ES, Ren JF, Marchlinski FE.; Circulation. 2009;120:366-375 26.Combined endocardial and epicardial catheter ablation in arrhythmogenic right ventricular dysplasia incorporating scar dechanneling technique / clinical perspective. Berruezo A, Fernández-Armenta J, Mont L, Zeljko H, Andreu D, Herczku C, Boussy T, Tolosana JM, Arbelo E, Brugada J.; Circulation: Arrhythmia and Electrophysiology. 2012;5:111-121
Juan Fernández-Armenta, MD and Josep Brugada, MD, PhD Authors' disclosures: None declared
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