Skip to main content
PMC home page
British Heart Journal logoLink to British Heart Journal
. 1987 May;57(5):436–445. doi: 10.1136/hrt.57.5.436

Clinical, haemodynamic, and antiarrhythmic effects of long term treatment with amiodarone of patients in heart failure.

J G Cleland, H J Dargie, I N Findlay, J T Wilson
PMCID: PMC1277198  PMID: 3297121

Abstract

Twenty two patients with heart failure were studied in a double blind crossover trial to compare amiodarone (200 mg/day) with placebo. Each agent was given for three months. Extrasystoles and complex ventricular arrhythmias were common during ambulatory electrocardiographic monitoring and during exercise testing at entry to the study. Breathlessness and tiredness as assessed by visual analogue scores and duration of treadmill exercise did not become worse during amiodarone treatment. During the placebo and amiodarone phases of the study left ventricular ejection fraction and cardiac index determined by first pass radionuclide ventriculography were similar, both at rest and during upright bicycle exercise. Exercise induced ventricular tachycardia was abolished and simple and complex ventricular arrhythmias observed on 24 hour ambulatory monitoring were greatly diminished during amiodarone treatment. Three patients died, all suddenly, during the placebo phase. In two patients amiodarone was withdrawn after a further myocardial infarction in one and a worsening of symptoms of ventricular arrhythmia in the other. In contrast with other antiarrhythmic agents amiodarone is effective in suppressing ventricular arrhythmias in heart failure without causing adverse haemodynamic effects. Because frequent ventricular arrhythmias are known to be associated with a poor prognosis in heart failure, these data suggest that amiodarone may improve the poor prognosis in patients with heart failure.

Full text

PDF
436

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atkinson A. B., Morton J. J., Brown J. J., Davies D. L., Fraser R., Kelly P., Leckie B., Lever A. F., Robertson J. I. Captopril in clinical hypertension. Changes in components of renin-angiotensin system and in body composition in relation to fall in blood pressure with a note on measurement of angiotensin II during converting enzyme inhibition. Br Heart J. 1980 Sep;44(3):290–296. doi: 10.1136/hrt.44.3.290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ball S. G., Tree M., Morton J. J., Inglis G. C., Fraser R. Circulating dopamine: its effect on the plasma concentrations of catecholamines, renin, angiotensin, aldosterone and vasopressin in the conscious dog. Clin Sci (Lond) 1981 Oct;61(4):417–422. doi: 10.1042/cs0610417. [DOI] [PubMed] [Google Scholar]
  3. Bellotti G., Silva L. A., Esteves Filho A., Rati M., de Moraes A. V., Ramires J. A., da Luz P., Pileggi F. Hemodynamic effects of intravenous administration of amiodarone in congestive heart failure from chronic Chagas' disease. Am J Cardiol. 1983 Nov 1;52(8):1046–1049. doi: 10.1016/0002-9149(83)90529-5. [DOI] [PubMed] [Google Scholar]
  4. Chakko C. S., Gheorghiade M. Ventricular arrhythmias in severe heart failure: incidence, significance, and effectiveness of antiarrhythmic therapy. Am Heart J. 1985 Mar;109(3 Pt 1):497–504. doi: 10.1016/0002-8703(85)90554-x. [DOI] [PubMed] [Google Scholar]
  5. Charlier R. Cardiac actions in the dog of a new antagonist of adrenergic excitation which does not produce competitive blockade of adrenoceptors. Br J Pharmacol. 1970 Aug;39(4):668–674. doi: 10.1111/j.1476-5381.1970.tb09892.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cleland J. G., Dargie H. J., Pettigrew A., Gillen G., Robertson J. I. The effects of captopril on serum digoxin and urinary urea and digoxin clearances in patients with congestive heart failure. Am Heart J. 1986 Jul;112(1):130–135. doi: 10.1016/0002-8703(86)90690-3. [DOI] [PubMed] [Google Scholar]
  7. Cobbe S. M., Manley B. S. Cellular electrophysiology of amiodarone in cardiac ischaemia. Br J Clin Pract Suppl. 1986 Apr;44:104–108. [PubMed] [Google Scholar]
  8. Cohn J. N., Levine T. B., Olivari M. T., Garberg V., Lura D., Francis G. S., Simon A. B., Rector T. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med. 1984 Sep 27;311(13):819–823. doi: 10.1056/NEJM198409273111303. [DOI] [PubMed] [Google Scholar]
  9. Côté P., Bourassa M. G., Delaye J., Janin A., Froment R., David P. Effects of amiodarone on cardiac and coronary hemodynamics and on myocardial metabolism in patients with coronary artery disease. Circulation. 1979 Jun;59(6):1165–1172. doi: 10.1161/01.cir.59.6.1165. [DOI] [PubMed] [Google Scholar]
  10. Debbas N. M., Du Cailar C., Sassine A., Derancourt J., Demaille J. G., Puech P. Determination of cardiac and plasma drug levels during long-term amiodarone therapy. Eur J Clin Invest. 1983 Apr;13(2):123–127. doi: 10.1111/j.1365-2362.1983.tb00076.x. [DOI] [PubMed] [Google Scholar]
  11. Debbas N. M., du Cailar C., Bexton R. S., Demaille J. G., Camm A. J., Puech P. The QT interval: a predictor of the plasma and myocardial concentrations of amiodarone. Br Heart J. 1984 Mar;51(3):316–320. doi: 10.1136/hrt.51.3.316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ellenbogen K. A., O'Callaghan W. G., Colavita P. G., Smith M. S., German L. D. Cardiac function in patients on chronic amiodarone therapy. Am Heart J. 1985 Aug;110(2):376–381. doi: 10.1016/0002-8703(85)90159-0. [DOI] [PubMed] [Google Scholar]
  13. Ferlinz J., Easthope J. L., Aronow W. S. Effects of verapamil on myocardial performance in coronary disease. Circulation. 1979 Feb;59(2):313–319. doi: 10.1161/01.cir.59.2.313. [DOI] [PubMed] [Google Scholar]
  14. Finerman W. B., Jr, Hamer A., Peter T., Weiss D., Mandel W. J. Electrophysiologic effects of chronic amiodarone therapy in patients with ventricular arrhythmias. Am Heart J. 1982 Nov;104(5 Pt 1):987–996. doi: 10.1016/0002-8703(82)90430-6. [DOI] [PubMed] [Google Scholar]
  15. Franciosa J. A., Wilen M., Ziesche S., Cohn J. N. Survival in men with severe chronic left ventricular failure due to either coronary heart disease or idiopathic dilated cardiomyopathy. Am J Cardiol. 1983 Mar 1;51(5):831–836. doi: 10.1016/s0002-9149(83)80141-6. [DOI] [PubMed] [Google Scholar]
  16. Fraser R., Guest S., Young J. A comparison of double-isotope derivative and radioimmunological estimation of plasma aldosterone concentration in man. Clin Sci Mol Med. 1973 Sep;45(3):411–415. doi: 10.1042/cs0450411. [DOI] [PubMed] [Google Scholar]
  17. Gagnol J. P., Devos C., Clinet M., Nokin P. Amiodarone. Biochemical aspects and haemodynamic effects. Drugs. 1985 Mar;29 (Suppl 3):1–10. doi: 10.2165/00003495-198500293-00002. [DOI] [PubMed] [Google Scholar]
  18. Greene H. L., Graham E. L., Werner J. A., Sears G. K., Gross B. W., Gorham J. P., Kudenchuk P. J., Trobaugh G. B. Toxic and therapeutic effects of amiodarone in the treatment of cardiac arrhythmias. J Am Coll Cardiol. 1983 Dec;2(6):1114–1128. doi: 10.1016/s0735-1097(83)80338-6. [DOI] [PubMed] [Google Scholar]
  19. Harris L., McKenna W. J., Rowland E., Holt D. W., Storey G. C., Krikler D. M. Side effects of long-term amiodarone therapy. Circulation. 1983 Jan;67(1):45–51. doi: 10.1161/01.cir.67.1.45. [DOI] [PubMed] [Google Scholar]
  20. Holmes J., Kubo S. H., Cody R. J., Kligfield P. Arrhythmias in ischemic and nonischemic dilated cardiomyopathy: prediction of mortality by ambulatory electrocardiography. Am J Cardiol. 1985 Jan 1;55(1):146–151. doi: 10.1016/0002-9149(85)90317-0. [DOI] [PubMed] [Google Scholar]
  21. Holt D. W., Tucker G. T., Jackson P. R., Storey G. C. Amiodarone pharmacokinetics. Am Heart J. 1983 Oct;106(4 Pt 2):840–847. doi: 10.1016/0002-8703(83)90006-6. [DOI] [PubMed] [Google Scholar]
  22. Josephson M. A., Kaul S., Hopkins J., Kvam D., Singh B. N. Hemodynamic effects of intravenous flecainide relative to the level of ventricular function in patients with coronary artery disease. Am Heart J. 1985 Jan;109(1):41–45. doi: 10.1016/0002-8703(85)90413-2. [DOI] [PubMed] [Google Scholar]
  23. Kaski J. C., Girotti L. A., Messuti H., Rutitzky B., Rosenbaum M. B. Long-term management of sustained, recurrent, symptomatic ventricular tachycardia with amiodarone. Circulation. 1981 Aug;64(2):273–279. doi: 10.1161/01.cir.64.2.273. [DOI] [PubMed] [Google Scholar]
  24. Kudenchuk P. J., Pierson D. J., Greene H. L., Graham E. L., Sears G. K., Trobaugh G. B. Prospective evaluation of amiodarone pulmonary toxicity. Chest. 1984 Oct;86(4):541–548. doi: 10.1378/chest.86.4.541. [DOI] [PubMed] [Google Scholar]
  25. Maheswaran R., Bramble M. G., Hardisty C. A. Massive digoxin overdose: successful treatment with intravenous amiodarone. Br Med J (Clin Res Ed) 1983 Aug 6;287(6389):392–393. doi: 10.1136/bmj.287.6389.392-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McKee P. A., Castelli W. P., McNamara P. M., Kannel W. B. The natural history of congestive heart failure: the Framingham study. N Engl J Med. 1971 Dec 23;285(26):1441–1446. doi: 10.1056/NEJM197112232852601. [DOI] [PubMed] [Google Scholar]
  27. McKenna W. J., Krikler D. M., Goodwin J. F. Arrhythmias in dilated and hypertrophic cardiomyopathy. Med Clin North Am. 1984 Jul;68(4):983–1000. doi: 10.1016/s0025-7125(16)31110-5. [DOI] [PubMed] [Google Scholar]
  28. McKenna W. J., Rowland E., Krikler D. M. Amiodarone: the experience of the past decade. Br Med J (Clin Res Ed) 1983 Dec 3;287(6406):1654–1656. doi: 10.1136/bmj.287.6406.1654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Meinertz T., Hofmann T., Kasper W., Treese N., Bechtold H., Stienen U., Pop T., Leitner E. R., Andresen D., Meyer J. Significance of ventricular arrhythmias in idiopathic dilated cardiomyopathy. Am J Cardiol. 1984 Mar 15;53(7):902–907. doi: 10.1016/0002-9149(84)90522-8. [DOI] [PubMed] [Google Scholar]
  30. Milner P. G., Platia E. V., Reid P. R., Griffith L. S. Ambulatory electrocardiographic recordings at the time of fatal cardiac arrest. Am J Cardiol. 1985 Oct 1;56(10):588–592. doi: 10.1016/0002-9149(85)91016-1. [DOI] [PubMed] [Google Scholar]
  31. Moysey J. O., Jaggarao N. S., Grundy E. N., Chamberlain D. A. Amiodarone increases plasma digoxin concentrations. Br Med J (Clin Res Ed) 1981 Jan 24;282(6260):272–272. doi: 10.1136/bmj.282.6260.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pfisterer M., Burkart F., Müller-Brand J., Kiowski W. Important differences between short- and long-term hemodynamic effects of amiodarone in patients with chronic ischemic heart disease at rest and during ischemia-induced left ventricular dysfunction. J Am Coll Cardiol. 1985 May;5(5):1205–1211. doi: 10.1016/s0735-1097(85)80026-7. [DOI] [PubMed] [Google Scholar]
  33. Reddy C. P., Gettes L. S. Use of isoproterenol as an aid to electric induction of chronic recurrent ventricular tachycardia. Am J Cardiol. 1979 Oct;44(4):705–713. doi: 10.1016/0002-9149(79)90291-1. [DOI] [PubMed] [Google Scholar]
  34. Robinson C., Jackson G., Fisk C., Jewitt D. Haemodynamic effects of atenolol in patients with coronary artery disease. Br Heart J. 1978 Jan;40(1):22–28. doi: 10.1136/hrt.40.1.22. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sanmartí A., Permanyer-Miralda G., Castellanos J. M., Foz-Sala M., Galard R. M., Soler-Soler J. Chronic administration of amiodarone and thyroid function: a follow-up study. Am Heart J. 1984 Nov;108(5):1262–1268. doi: 10.1016/0002-8703(84)90751-8. [DOI] [PubMed] [Google Scholar]
  36. Schwartz A., Shen E., Morady F., Gillespie K., Scheinman M., Chatterjee K. Hemodynamic effects of intravenous amiodarone in patients with depressed left ventricular function and recurrent ventricular tachycardia. Am Heart J. 1983 Oct;106(4 Pt 2):848–856. doi: 10.1016/0002-8703(83)90007-8. [DOI] [PubMed] [Google Scholar]
  37. Sclarovsky S., Lewin R. F., Kracoff O., Strasberg B., Arditti A., Agmon J. Amiodarone-induced polymorphous ventricular tachycardia. Am Heart J. 1983 Jan;105(1):6–12. doi: 10.1016/0002-8703(83)90270-3. [DOI] [PubMed] [Google Scholar]
  38. Shapiro W. Correlative studies of serum digitalis levels and the arrhythmias of digitalis intoxication. Am J Cardiol. 1978 May 1;41(5):852–859. doi: 10.1016/0002-9149(78)90724-5. [DOI] [PubMed] [Google Scholar]
  39. Singh B. N., Jewitt D. E., Downey J. M., Kirk E. S., Sonnenblick E. H. Effects of amiodarone and L8040, novel antianginal and antiarrhythmic drugs, on cardiac and coronary haemodynamics and on cardiac intracellular potentials. Clin Exp Pharmacol Physiol. 1976 Sep-Oct;3(5):427–442. doi: 10.1111/j.1440-1681.1976.tb00620.x. [DOI] [PubMed] [Google Scholar]
  40. Singh B. N., Vaughan Williams E. M. The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol. 1970 Aug;39(4):657–667. doi: 10.1111/j.1476-5381.1970.tb09891.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sutton R. Haemodynamics of intravenous disopyramide. J Int Med Res. 1976;4(1 Suppl):46–48. [PubMed] [Google Scholar]
  42. Taylor S. H., Silke B. Haemodynamic effects of beta-blockade in ischaemic heart failure. Lancet. 1981 Oct 17;2(8251):835–837. doi: 10.1016/s0140-6736(81)91105-3. [DOI] [PubMed] [Google Scholar]
  43. Trobaugh G. B., Kudenchuk P. J., Greene H. L., Tutt R. C., Kingston E., Gorham J. R., Gross B. W., Graham E. L., Sears G. K., Werner J. A. Effect of amiodarone on ventricular function as measured by gated radionuclide angiography. Am J Cardiol. 1984 Dec 1;54(10):1263–1266. doi: 10.1016/s0002-9149(84)80077-6. [DOI] [PubMed] [Google Scholar]
  44. Unverferth D. V., Magorien R. D., Moeschberger M. L., Baker P. B., Fetters J. K., Leier C. V. Factors influencing the one-year mortality of dilated cardiomyopathy. Am J Cardiol. 1984 Jul 1;54(1):147–152. doi: 10.1016/0002-9149(84)90320-5. [DOI] [PubMed] [Google Scholar]
  45. Waagstein F., Hjalmarson A., Varnauskas E., Wallentin I. Effect of chronic beta-adrenergic receptor blockade in congestive cardiomyopathy. Br Heart J. 1975 Oct;37(10):1022–1036. doi: 10.1136/hrt.37.10.1022. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. von Olshausen K., Schäfer A., Mehmel H. C., Schwarz F., Senges J., Kübler W. Ventricular arrhythmias in idiopathic dilated cardiomyopathy. Br Heart J. 1984 Feb;51(2):195–201. doi: 10.1136/hrt.51.2.195. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Heart Journal are provided here courtesy of BMJ Publishing Group

RESOURCES