Amiodaron-induzierte Pneumonitis bei dilatativer Kardiomyopathie

Zusammenfassung

Hintergrund: Amiodaron (Cordarex®) ist ein Klasse-III-Antiarrhythmikum, das zur Behandlung von ventrikulären und supraventrikulären Tachykardien eingesetzt wird. Eine seltene, aber potentiell lebensbedrohliche Nebenwirkung von Amiodaron ist die pulmonale Toxizität, die zur Lungenfibrose führen kann. Kasuistik: Wir berichten über zwei Patienten mit dilatativer Kardiomyopathie (DCM), die wegen symptomatischer nicht anhaltender Kammertachykardien bzw. anhaltender Kammertachykardien mit Amiodaron behandelt wurden. Nach 6 Wochen bzw. 8 Monaten Behandlungsdauer entwickelten beide Patienten eine Amiodaron-induzierte Pneumonitis mit progredienter Dyspnoe. Andere Ursachen für eine Pneumonitis wurden bei beiden Patienten mittels Bronchoskopie, broncho-alveolärer Lavage und transbronchialer Biopsie ausgeschlossen. In beiden Fällen waren die Lungenveränderungen nach Absetzen der Amiodarontherapie weitgehend reversibel. Schlussfolgerungen: Amiodaron-induzierte Lungenveränderungen sind seltene, aber möglicherweise lebensbedrohliche Komplikationen dieser Therapie. Bei Patienten mit DCM und fortgeschrittener Herzinsuffizienz sind Amiodaron-induzierte Lungenveränderungen klinisch nur schwer zu erkennen, da die Symptome kaum von einer Progredienz der Herzinsuffizienz zu unterscheiden sind. Bei einer Verschlechterung der regelmäßig zu kontrollierenden Lungendiffusionskapazität sollten weiterführende diagnostische Maßnahmen einschließlich Bronchoskopie mit broncho-alveolärer Lavage und Biopsie durchgeführt werden.

Abstract

Background: Antiarrhythmic therapy with class III drug amiodarone (Cordarex®) for supraventricular and ventricular tachycardia is commonly used because of its high efficacy and absent negative inotropy. Pulmonary toxicity of amiodarone possibly leading to lung fibrosis is a rare, but severe side effect of chronic therapy. In contrast to patients with coronary artery disease, there are only a few data about pulmonary toxicity in patients with dilated cardiomyopathy. Case report: We report on two patients with dilated cardiomyopathy who received amiodarone because of symptomatic non-sustained or sustained ventricular tachycardia. After 6 weeks resp. 8 months of treatment with amiodarone both patients developed pulmonary toxicity. Other causes of pulmonary toxicity were ruled out by bronchoscopy, bronchoalveolar lavage and biopsy. Pulmonary function improved in both patients within some weeks after discontinuation of amiodarone. Conclusions: This report deals with two cases of amiodarone induced pulmonary toxicity in dilated cardiomyopathy leading to respiratory insufficiency. Pulmonary toxicity is a rare, but potentially lethal side effect of amiodarone. Reversibility of pulmonary changes in case of an early drug discontinuation is shown. Because of severe reduced left ventricular function in dilated cardiomyopathy, heart failure symptoms could conceal clinical signs of pulmonary amiodarone toxicity. Therefore, pulmonary function should be controlled periodically during amiodarone therapy including bronchoscopy, bronchoalveolar lavage, biopsy and measurement of diffusion capacity.

Literatur

• 1 Burckhardt D, Hoffmann A, Kiowski W, Pfisterer M, Burkart F. Effect of antiarrhythmic therapy on mortality after myocardial infarction.  J Cardiovasc Pharmacol. 1991;  17 Suppl 6 S77-S81
• 2 Cairns J A, Connolly S J, Gent M, Roberts R. Post-myocardial infarction mortality in patients with ventricular premature depolarizations. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Pilot Study.  Circulation. 1991;  84(2) 550-557
• 3 Cairns J A, Connolly S J, Roberts R, Gent M. Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators.  Lancet. 1997;  349(9053) 675-682
• 4 Doval H C, Nul D R, Grancelli H O, Perrone S V, Bortman G R, Curiel R. Randomised trial of low-dose amiodarone in severe congestive heart failure. Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiaca en Argentina (GESICA).  Lancet. 1994;  344(8921) 493-498
• 5 Julian D G, Camm A J, Frangin G, Janse M J, Munoz A, Schwartz P J. et al . Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction: EMIAT. European Myocardial Infarct Amiodarone Trial Investigators.  Lancet. 1997;  349(9053) 667-674
• 6 Massie B M, Fisher S G, Radford M, Deedwania P C, Singh B N, Fletcher R D. et al . Effect of amiodarone on clinical status and left ventricular function in patients with congestive heart failure. CHF-STAT Investigators.  Circulation. 1996;  93(12) 2128-2134
• 7 Mulligan D C, McHenry C R, Kinney W, Esselstyn Jr C B. Amiodarone-induced thyrotoxicosis: clinical presentation and expanded indications for thyroidectomy.  Surgery. 1993;  114(6) 1114-1119
• 8 Harris L, McKenna W J, Rowland E, Krikler D M. Side effects and possible contraindications of amiodarone use.  Am Heart J. 183;  106(4 Pt 2) 916-923
• 9 Hilleman D, Miller M A, Parker R, Doering P, Pieper J A. Optimal management of amiodarone therapy: efficacy and side effects.  Pharmacotherapy. 1998;  18(6 Pt 2) 138S-145S
• 10 McGovern B, Garan H, Ruskin J N. Serious adverse effects of amiodarone.  Clin Cardiol. 1984;  7(3) 131-137
• 11 McKenna W J, Rowland E, Krikler D M. Amiodarone: the experience of the past decade.  Br Med J (Clin Res Ed). 1983;  287(6406) 1654-1656
• 12 Quyyumi A A, Ormerod L P, Clarke S W, Evans T R, Ward R L. Pulmonary fibrosis - a serious side-effect of amiodarone therapy.  Eur Heart J. 1983;  4(7) 521-524
• 13 Sobol S M, Rakita L. Pneumonitis and pulmonary fibrosis associated with amiodarone treatment: a possible complication of a new antiarrhythmic drug.  Circulation. 1982;  65(4) 819-824
• 14 Singh S N, Fletcher R D, Fisher S, Lazzeri D, Deedwania P, Lewis D. et al . Veterans Affairs congestive heart failure antiarrhythmic trial CHF STAT Investigators.  Am J Cardiol. 1993;  72(16) 99F-102F
• 15 Singh S N, Fisher S G, Deedwania P C, Rohatgi P, Singh B N, Fletcher R D. Pulmonary effect of amiodarone in patients with heart failure. The Congestive Heart Failure-Survival Trial of Antiarrhythmic Therapy (CHF-STAT) Investigators (Veterans Affairs Cooperative Study No. 320).  J Am Coll Cardiol. 1997;  30(2) 514-517
• 16 Roca J, Heras M, Rodriguez-Roisin R, Magrina J, Xaubet A, Sanz G. Pulmonary compliations after long term amiodarone treatment.  Thorax. 1992;  47(5) 372-376
• 17 Dusman R E, Stanton M S, Miles W M, Klein L S, Zipes D P, Fineberg N S. et al . Clinical features of amiodarone-induced pulmonary toxicity.  Circulation. 1990;  82(1) 51-59
• 18 Camus P, Lombard J N, Perrichon M, Piard F, Guerin J C, Thivolet F B. et al . Bronchiolitis obliterans organising pneumonia in patients taking acebutolol or amiodarone.  Thorax. 1989;  44(9) 711-715
• 19 Lambert M, Hebbar M, Viget N, Hatron P Y, Hachulla E, Devulder B. [Bronchiolitis obliterans with organized pneumonia: a rare complication of primary Gougerot-Sjogren syndrome].  Rev Med Interne. 2000;  21(1) 74-77
• 20 Martin W J, Rosenow E C. III. Amiodarone pulmonary toxicity. Recognition and pathogenesis (Part 2).  Chest. 1998;  93(6) 1242-1248
• 21 Martin W J. Pulmonary toxicity induced by chemical agents.  Eur Respir J. 1990;  3(3) 375-376
• 22 Martin W J. Mechanisms of amiodarone pulmonary toxicity.  Clin Chest Med. 1990;  11(1) 131-138
• 23 Martin W J. Pharmacologic and other chemical causes of interstitial lung disease.  Chest. 1991;  100(1) 241-243
• 24 Xaubet A, Roca J, Rodriguez-Roisin R, Herranz J, Marin A, Lomena F. et al . Bronchoalveolar lavage cellular analysis and gallium lung scan in the assessment of patients with amiodarone-induced pneumonitis.  Respiration. 1987;  52(4) 272-280
• 25 Akoun G M, Gauthier-Rahman S, Milleron B J, Perrot J Y, Mayaud C M. Amiodarone-induced hypersensitivity pneumonitis. Evidence of an immunological cell-mediated mechanism.  Chest. 1984;  85(1) 133-135
• 26 Karpel J P, Mitsudo S, Norin A J. Natural killer cell activity in a rat model of amiodarone-induced interstitial lung disease.  Chest. 1991;  99(1) 230-234
• 27 Fan K, Bell R, Eudy S, Fullenwider J. Amiodarone-associated pulmonary fibrosis. Evidence of an immunologically mediated mechanism.  Chest. 1987;  92(4) 625-630
• 28 Olivieri D, Pesci A, Bertorelli G. Eosinophilic alveolitis in immunologic interstitial lung disorders.  Lung. 1990;  168 Suppl 964-973
• 29 Pozzi E, Sada E, Luisetti M, De R V, Scelsi M. Interstitial pneumpathy and low-dosage amiodarone.  Eur J Respir Dis. 1984;  65(8) 620-622
• 30 Jessurun G A, Crijns H J. Amiodarone pulmonary toxicity.  BMJ. 1997;  314(7081) 619-620
• 31 Jessurun G A, Boersma W G, Crijns H J. Amiodarone-induced pulmonary toxicity. Predisposing factors, clinical symptoms and treatment.  Drug Saf. 1998;  18(5) 339-344
• 32 Pollak P T. Clinical organ toxicity of antiarrhythmic compounds: ocular and pulmonary manifestations.  Am J Cardiol. 1999;  84(9A) 37R-45R
• 33 Woosley R L, Echt D S, Roden D M. Effects of congestive heart failure on the pharmacokinetics and pharmacodynamics of antiarrhythmic agents.  Am J Cardiol. 1986;  57(3) 25B-33B
• 34 Zipes D P, Prystowsky E N, Heger J J. Amiodarone: electrophysiologic actions, pharmacokinetics and clinical effects.  J Am Coll Cardiol. 1984;  3(4) 1059-1071