There are no controlled clinical trials evaluating drug therapy in patients with ventricular arrhythmias and chronic chagasic cardiomyopathy. Empirical treatment with disopyramide (400-1,000mg/d), phenytoin (4-6mg/d), mexiletine (600-1,200mg/d), propafenone (900mg/d), amiodarone ( loading: 1,000mg/d, 10-14 days; maintenance 200-600mg/d), and sotalol (320mg/d) had efficacy and tolerance ranging from 18% to 90% with heterogeneous criteria for efficacy definition. Further studies with homogenous criteria are required to determine which is the most appropriate drug therapy for patients with chronic chagasic cardiomyopathy and ventricular arrhythmias.Apesar da grande importância da cardiopatia chagásica em nosso meio, não existem estudos clínicos controlados que avaliem adequadamente as opções terapêuticas nessa patologia. Foram testadas disopiramida (400-1.000 mg/dia), difenil hidantoína (4-6 mg/kg/dia), mexiletine (600-1.200 mg/d), propafenona (900 mg/d), amiodarona (impregnação: 1.000 mg/dia/ 10-14 dias; manutenção: 200-600 mg/d) e sotalol (320 mg/dia) com níveis de eficácia e tolerância variando de 18 a 90% dependendo das definições empregadas. Estudos comparativos controlados poderão esclarecer futuramente as melhores estratégias farmacológicas para o tratamento dessa entidade nosológica.Escola Paulista de Medicina Clinical Cardiac ElectrophysiologyUNIFESP, EPM, Clinical Cardiac ElectrophysiologySciEL

De Paola, Angelo Amato Vincenzo

Gondin, Fernando Antonio Aquino

Hara, Vanderlei

Mendonça, Alayde

Sao Paulo Medical Journal

De Paola, Angelo Amato Vincenzo [UNIFESP]

Gondin, Fernando Antonio Aquino [UNIFESP]

Hara, Vanderlei [UNIFESP]

Mendonça, Alayde [UNIFESP]

Repositório Institucional UNIFESP

Angelo Amato V.de Paola, Fernando Antonio Aquino Gondin,Vanderlei Hara, Alayde Mendon9aMedical treatment of cardiac arrhythmias in"Chagas'heart diseaseClinical Cardiac Electrophysiology, Escola Paulista deM edicina - sao Paulo, BrazilThere are no controlled clinical trials evaluating drug therapy in patients with ventricular arrhythmias and chronic chagasiccardiomyopathy. Empirical treatment with disopyramide (400-1,OOOmg/d),phenytoin (4-6mg/d), mexiletine (600-1,200mg/d),propafenone (900mg/d), amiodarone ( loading: 1,OOOmg/d,10-14 days; maintenance 200-600mg/d), and sotalol (320mg/d) hadefficacy and tolerance ranging from 18% to 90% with heterogeneous criteria for efficacy definition. Further studies withhomogenous criteria are required to determine which is the most appropriate drug therapy for patients with chronic chagasiccardiomyopathy and ventricular arrhythmias.UNITERMS: Chronic chagasic cardiomyopathy. Cardiac arrhythmia. Antiarrhythmic drugs.INTRODUCTIONThe objectives of the treatment of cardiacarrhythmias are relief of symptoms and preventionof sudden cardiac death. The therapeuticalgorithms are born from controlled clinical studies, whereAddress for correspondence: 'Angelo Amato V. de PaolaSetor de Eletrofisiologia ClfnicaEscola Paulista de MedicinaRua Napoleao de Barros, 593Sao Paulo - SP - Brasil - CEP 04024-002efficacy and tolerance of these drugs are convenientlytested in human beings. These information do not havethe mistakes originated from clinical reasoning.The results of controlled clinical trials have importantinfluence in scientific community, sometimesdemonstrating that decisions guided only by clinicalintuition can be dangerous to the patients. A well-knownexample occurred during the CAST study. It wasdemonstrated that patients treated with cl ass ICantiarrhythmic drugs, which are potent antiarrhythmicagents for ventricular arrhythmias, had two to threefoldincrease in the number of deaths when compared withthose who received placebo (28).The majority of these studies deri ved from patientswith ischemic cardiomyopathy after myocardial infarction.Unfortunately, there are few relevant studies in our country858 S~o Paulo Medical Journal/RPM 113(2) Mar/Apr 1995evaluating patients with Chagas' disease when the use ofan antiarrhythmic drug is to be considered.CLASS IANTIARRHYTHMIC DRUGSGroup IA drugs: Only procainamide, quinidine anddisopyramide are commercially available in Brazil. Thereare no adequate studies evaluating the use of such drugsin Chagas' disease.Slow-release procainamide is not available in Brazil.Given intravenously, it is useful during an episode ofsustained ventricular tachycardia. A total dose of 20mg/Kg is administered at an infusion rate of 50mg/min.Quinidine, is commercially available in 200 mgtablets for oral administration every 6 hour, in doses of800-1,600mg/day. It reduces premature ventricular beatsin 36-70% of the patients.Disopyramide is commercially available in 100 and250mg. Drug discontinuation is mandatory in 9% of thepatients due to symptomatic bradyarrhythmias( 1,22).Worsening of congestive heart failure, a condition verycommon in chagasic cardiomyopathy, limits its use inpatients with ventricular dysfunction (19).Group IB drugs: Lidocaine, mexiletine, andphenytoin are commercially available in our country. Whenintravenous administration is imperative and the ventriculararrhythmia is not responsive to procainamide, lidocainecan be used. The loading dose is 1-2mg/kg and themaintenance dose ranges from 20 to 60mcg/kg/min.Mexiletine is available in tablets of 200ing, and the dailydoses ranges from 600 to 1,200mg divided in 3 times doses.Premature ventricular complex suppression was achievedin 32%-69% but 19% of these patients had side effects(14,15,27). Phenytoin is given orally, in doses of 4-6mg/kg/day (3 times daily) and efficacy was demonstrated in18% of 11 patients tested (27).Group Ie Drugs: Flecainide and encainide weredescribed as potent suppressers of premature ventricularbeats (2). However, a subsequent multicentric trial showedthat these drugs should not be administered in patientswith poor left ventricular function (9,28). Propafenone,another IC drug, is utilized orally (900mg/day), 3 timesdaily with efficacy and tolerance in 41 %-66% (5,20).It is important to stress that metanalysis of controlledstudies of group I drugs in patients with ischemiccardiomyopathy delineated an increase in mortality inpatients treated with these drugs when compared with aplacebo group (29). Their use in chagasic cardiomyopathy,is indicated only to' relief symptoms in selected cases.CLASS IIANTIARRHYTHMIC DRUGSIn spite of being the most effective drugs inpreventing sudden cardiac death (29), the beta blocker haveonly moderate efficacy in controlling ventriculararrhythmias (39-56%). There are no clinical studies withthese drugs in Chagas' disease: alterations in automatism,conduction and left ventricular dysfunction, will restrictthe use of these drugs only for selected cases.CLASS IIIANTIARRHYTHMIC DRUGSExperimental data and results of clinical studieschanged the trends of using sodium channel blocker (classI drugs) to drugs that prolong the repolarization time (classIII drugs). At the present time, there is not a drug withexclusive class III action in clinical use. Amiodarone, adrug with multiple actions, and sotalol, a non selectivebeta blocker, have potent class III action, and are includedin this group.Amiodarone has been empirically used in our countryin all kinds of arrhythmias. Unfortunately there are nocontrolled studies evaluating efficacy of this drug inchagasic cardiomyopathy. In non-controlled studies, thenumber of premature ventricular beats decreased in 35-92% of the patients evaluated with few side effects(3,4,13,21). The doses utilized in the majority of studiesvaried from 600 to 1,200 mg for 14 days (loading phase),followed by a medium doses of 400mg (maintenancephase).Patients with chronic chagasic cardiomyopathy andsustained ventricular tachycardia are at major risk forsudden death. In our experience, criteria of efficacyaccording to Holter monitoring was found in 52% ofpatients. When electrophysiologic study was used to assessefficacy, ventricular tachycardia was not reinducible in18% of the patients (11). None of these methods was ableto predict clinical efficacy of this drug. The worst prognosisduring amiodarone therapy was observed in patients withcongestive heart failure (6,24).Sotalol, another class III antiarrhythmic drug, alsohas a beta-blocker action, had better efficacy and tolerancethan class I drugs (16). This drug was recently reintroducedin our country, and we observed 67% efficacy in 14 patientswith Chagas' disease and sustained ventricular tachycardiarefractory to drug therapy (12). Like amiodarone, its usemust be extremely cautious in patients withbradyarrhythmias.Sao Paulo Medical Journal/RPM 113(2) Mar/Apr 1995 859Finally, it is important to stress that ventricularfunction is the most important clinical variable influencingthe prognosis of patients with Chagas' disease and complexventricular arrhythmias (17,18). Patients with refractoryventricular arrhythmias, specially sustained ventriculartachycardias can be studied with the electrophysiological(7) techniques. Surgical (26) or catheter ablation (10) ofan arrhythmogenic focus of ventricular tachycardia andimplantation of a cardioverter-defibrillator can be indicatedin patients refractory to all therapeutic options (8).REFERENCES1. ALBANESI FILHO, EM.; DA ROCHA PJ.; BENCffiMOL,C.B.; GINEFRA, P. & BENCHIMOL, A.B. - Disopiramidano tratamento da extra-sistolia ventricular da cardiopatiachagasica cronica. Arq Bras Cardiol33: 453-8, 1979.2. CAPS investigators - The cardiac arrhytmia pilot study, AmJ Cardiol 57: 91-5, 1986.3. CARRASCO, H.A.; VICUNA, AV.; MOLINA, C. et al. -Effect of low oral doses of disopyramide and amiodarone onventricular and atrial arrhytmias of chagasic patients withadvanced myocardial damage. IntJ Cardiol9: 425-38, 1985.4. CHIALE, P.; HALPERN, S.; NAU, G.]. et al. - Efficacy ofamiodarone during long-term treatment of malignantventricular arrhytmias in patients with chronic chagasicmyocarditis. Am Heart J 107: 656-65, 1984.5. DA SILVA, M.AD.; FRAGATA FILHO, AA; BOAINAIN,E. & MAGALHA.ES, H.M. - Avalia~ao da propafenomaempacientes chagasicos com extra-sistolia ventricular. Arq BrasCardiol 36: 437-40, 1981.6. DEPAOLA, AA.V.; HOROWITZ, L.; SPIELMAN, S.R. etal. - Development of congestive heart failure and alterationsin left ventricular function in patients with sustainedventricular tachyarrhythmias treated with amiodarone. AmJ Cardiol 60: 276-80, 1987.7. DE PAOLA, A.A.V.; HOROWITZ, L.N.; MIYAMOTO,M.H. et al. - Angiographic and electrophysiologic substratesof ventricular tachycardia in chronic chagasic myocarditis.Am J Cardiol 65: 360-3, 1990.8. DE PAOLA, A.A.V.; HOROWITZ, L.N.; MIYAMOTO,M.H. et al. - Angiographic and electrophysiologic substratesof ventricular tachycardia in chronic chagasic myocarditis.Am Heart J 118: 415-7, 1989.860 Sao Paulo Medical Journal/RPM 113(2) Mar/Apr 19959. DE PAOLA, A.v.v.; HOROWITZ, L.N.; MORGANROTH,J. et al. - Influence of left ventricular dysfunction on f1ecainidetheraphy. J Am ColI Cardiol 9: 163-8, 1987.10. DE PAOLA, A.A.V.; GOMES, J.A.; SOUZA, LA.;PINHEIRO, R.; GUIGUER JR, N. & MARTINEZ FILHO,E.E. - Localization of the site of the origin of sustainedventricular tachycardia in chronic chagasic cardiomyopathy.PACE 16: 87 I, 1993.II. DE PAOLA, A.A.V.; GOMES, J.A.; SOUZA, LA.;VATTIMO, A.e.; GUIGUER JR, N. & MARTINEZ FILHO,E.E. - Efficacy of amiodarone in patients with ventriculartachycardia and chronic chagasic cardiomyopathy. J Am ColICardiol 23 (Suppl): 322A, 1994.12. GONDIN, EA.A.; DE PAOLA, A.A.V.; SILVA, R.M.EL.;METHA, N. & MARTINEZ FILHO, E.E. - Eficacia etolerancia do sotatol em pacientes com taquiarritmiasventriculares sustentadas. Arq Bras Cardiol 62: 64, 1994.13. GRECO, O.T.; LORGA, A.M.; GARZON, S.A.e. et al. - Aamiodarona nas arritmias ventriculares da cardiopatiachagasica cronica. Arq Bras Cardiol35: 177-81, 1980.14. JURADO, A.Z. & DE FEUILADE, N.D. - Empleo delmexiletine en las arritmias ventriculares de la cardiopatiachagasica. Prensa Med Argent 73: 665-73, 1986.15. LORGA, A.M.; GRECO, O.T.; GARZON, S.A.e. et al. -Mexitil no tratamento de arritmias ventriculares decardiopatas chagasicos cronicos. Rev Bras Med(Cardiologia) 2: 47-52, 1983.16. MASON, J.W. - For the ESVEM investigators. A comparisonof seven antiarrhythmie drugs in patients with ventriculartachyarrhythmias. N Engl J Med 329: 452-8, 1993.17. NETTO, O.S.; DE PAOLA, A.A.V.; MENDON(:A, A. et al.- Fatores relacionados com a ocorrencia de taquicardiaventricular ou 6bito em pacientes portadores de cardiopatiachagasica cronica. Arq Bras Cardiol 61: 19, 1993.18. PINHEIRO, R.; DE PAOLA, A.A.V.; MIYAMOTO, M.H.et al. - Morte subita em pacientes com cardiopatia chagasicacronica e taquicardia ventricular nao sustentada. Arq BrasCardiol 57: 134, 1991.19. PODRID, P.J.; SCHOENENBERGER, A. & LOWN, B. -Congestive heart failure caused by oral disopyramide. N EnglJ Med 302: 614-7, 1980.20. PORTO, e.e.; GUIMARAES, E.; ROSA, 1. & RASSI, A. -Propafenoma na prevenr;ao das extra-sfstoles ventricularesSao Paulo Medical Journal/RPM 113(2) Mar/Apr 1995de etiologia chagasica relacionadas com 0 esforr;o ffsico.Avaliar;ao por circloergometria. Arq Bras Cardiol39: 129-33, 1982.21. PRATA, A.P.; BATISTA, E.P. & PENHALVER, J.R. - Usode amiodarona em arritmias cardfacas de chagasicos cronicos.F Med(BR) 85: 7 I3-7, 1982.22. RASSI, A. & PERINI, G. - Ensaio cego com disopiramidano tratamento de extra-sistolia ventricular da cardiopatiachagasica cronica controlado atraves do sistema Holter deeletrocardiografia dinamica. Arq Bras Cardiol41: 72, 1983.23. ROSENBAUM, M.; POSSE, R.; SGAMMINI, H. et al. -Estudio c1inico multicentrico comparativo de la f1ecainida yla amiodarona en el tratamiento de las arritmias ventricularesasociadas a la cardiopatia chagasica cronica. Arch InstCardiol Mex 57: 325-30, 1987.24. SCANAVACCA, M.l.; SOSA, E.A.; LEE, J.H.; BELLOTTI,G. & PILEGGI, F. - Terapeutica empfrica com amiodaronaem portadores de miocardiopatia chagasica cronica etaquicardia ventricular sustentada. Arq Bras Cardiol 54:367-71, 1990.25. SGAMMINI, RO.; EVEQUOZ, M.e.; CHUIT, R.; ATTI,R.; SANTAMARINA, N.O. & KUSCHNIR, E. - Tratamientode las arritmias de alto riesgo de muerte subita en lacardiopatia chagasica cronica con mexiletine oral. Evaluacioncon monitoreo electrocardiografico ambulatorio de 24 h(Holter). Arq Bras Cardiol 40: 103-9, 1983.26. SOSA, E.; BARBERO, M.; SCALABRINI, A.; BELLOTTI,G.; JATENE, A. & PILEGGI, F. - Surgical treatment ofrecurrent ventricular tachycardia in chronic chagasic hemtdisease. (Abstractr book) Washington: X World Congressof Cardiology 1986. 117 p.27. SUAREZ-KURTZ, G.; LORGA, A.M. & MORAES, ED. -Effects of phenytoin on the ventricular tachyarrhythmias ofchronic Chagas' disease. Int J Cardiol 36: 81-6, 1992.28. The Cardiac Arrhytmia Suppression Trial (CAST)Investigators - Effect of encainide and f1ecainide on mortalityin a randomized trial of arrhythmia suppression aftermyocardial infarction. N Eng J Med 321: 406-12, 1989.29. YUSUF, S.; VENKATECH, G. & TEO, K.K. - Critical reviewof the approaches to the prevention of sudden death. Am JCardiol 72: 51-8, 1993.861

Medical treatment of cardiac arrhythmias in Chagas'heart disease

http://dx.doi.org/10.1590/S1516-31801995000200018

Medical treatment of cardiac arrhythmias in Chagas'heart disease

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