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Response of digoxin toxic atrial tachycardia to digoxin-specific Fab fragments
November
1.5, 1986
Responseof Digoxin Toxic Atrial Tachycardia to Digoxin-Specific Fab Fragments JOSEPH R. DESANTOLA, MD FRANCIS E. MARCHLINSKI, MD
D
igoxin-specific antibody fragments have been used successfully to safely treat ventricular ectopic activity, ventricular tachycardia, ventricular fibrillation, severe sinus bradycardia and atrioventricular block precipitated by excess digoxin.1-3 These arrhythmias in general have been reported to respond within 30 minutes of administration of digoxin-specific Fab fragments. We describe the time course and electrocardiographic response of a patient with digoxin toxic atria1 tachycardia to digoxin-specific Fab fragments.
THE AMERICAN
JOURNAL
OF CARDIOLOGY
Volume 58
1109
fore completion of the antibody fragment infusion. During the 70 minutes after infusion, the tachycardia rate gradually slowed to 83 beats/min and the PR interval progressively shortened (Fig. 1). The tachycardia then terminated and sinus rhythm resumed. The serum potassium level decreased from 5.4 mEq/liter immediately before the infusion to 4.5 mEq/liter 4 hours after the infusion. No adverse effects were observed. In the US., the results of digoxin-specific Fab fragment administration have been described in 63 patients.1-3 No previously reported patient had atria1 tachycardia. We have shown the efficacy of the antibody in controlling the atria1 tachyarrhythmias associated with digitalis excess. The arrhythmia did not
A 60-year-old man with idiopathic dilated cardiomyopathy, ejection fraction of 33% and paroxysmal atrial fibrillation was admitted to the hospital for evaluation of cutaneous and oral ulcers. Medications on admission included digoxin, 0.25 mg/day, quinidine sulfate, 300 mg every 6 hours, and isosorbide dinitrate, 40 mg/day. Blood pressure was lOO/SO mm/Hg and pulse was 60 beats/min. Precordial examination was unremarkable. Blood urea nitrogen was 61 mg/dl and creatinine 3.8 mg/dl. The electrocardiogram showed normal sinus rhythm at a rate of 65 beats/min, rare ventricular premature complexes, left anterior hemiblock and a nonspecific intraventricular conduction delay. The patient’s medications were continued without altering the dosage. On the third hospital day, the patient complained of nausea and vomited. Systolic blood pressure was 80 mm Hg. The electrocardiogram showed atriai tachycardia at a rate of 260 beats/min with 1:~ atrioventricular conduction and periods of variable block. Laboratory studies included a serum digoxin level of 4.0 rig/ml, creatinine 3.7 mg/dl, calcium 8.7 mg/dl, magnesium 1.9 mg/dl and potassium 5.4 mEq/liter. Intradermal skin testing and an intravenous challenge were performed with a small dose of purified ovine digoxin-specific Fab fragments. The patient was then treated with an intravenous infusion of 240 mg of the Fab fragments administered over 15 minutes. The tachycardia rate began to slow just be-
From the Clinical Electrophysiology Laboratory, Hospital of the University of Pennsylvania, and the Cardiovascular Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. This study was supported in part by grants from the American Heart Association, Southeastern Pennsylvania Chapter, Philadelphia, and grants HL28093 and HLO7346 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received January 10,1986; revised manuscript received April 3,1986, accepted April 8, 1986.
FIGURE 1. Electrocardiographic response to digoxin-specific Fab fragments. Toppanel, atrial tachycardia at a rate of 160 beats/min before Fab infusions. Subsequent panels show gradual slowing of atrial rate and PR interval shortening after Fab fragment infusion. Eighty minutes after Fab fragment administration, normal sinus rhythm resumed as evidenced by the altered P-wave morphologic characteristics.
1110
BRIEF REPORTS
promptly terminate, but gradually slowed beginning immediately and continuing during the 80 minutes after digoxin-specific Fab fragment infusion before terminating abruptly. Our observations are consistent with reports on the time course for reversal of other electrocardiographic manifestations of digoxin toxicity using digoxin-specific Fab fragments, although the maximum effect at 80 minutes is somewhat longer than that noted when reversing bradyarrhythmias. Our observation also may have implications with respect to the mechanism for atria1 tachycardia. Slowing of tachycardia with reversal of the toxic effects of digoxin is consistent with either triggered activity or abnormal automatic@ as the arrhythmia mechanisma4-”
Sinus Arrest with Intravenous Amiodarone ENRICO P. VELTRI, MD PHILIP R. REID, MD
A miodarone is a benzofuran derivative with potent electrophysiologic effects on the impulse generation and conduction system of the heart.1 The effects of amiodarone on the sinus node, in particular, are well described.z*3Sinus arrest4 and sinoatrial block5 with oral therapy have been demonstrated; we describe a patient with acute sinus arrest after intravenous amiodarone therapy. A 63-year-old woman with idiopathic dilated cardiomyopathy and ventricular tachyarrhythmias was admitted becauseof syncope. Five months earlier she had out-of-hospital cardiac arrest due to ventricular fibrillation. Baseline electrophysiologic study revealed normal sinus node recovery time and sinoatrial conduction; AH and HV intervals were normal. Sustained ventricular tachycardia was induced using proFrom the Divisions of Cardiology, Departments of Medicine, The Johns Hopkins Medical Institutions and Sinai Hospital, Baltimore, Maryland. Manuscript received February 4, 1986; revised manuscript received May 22, 1986, accepted May 26, 1986.
References 1. Smith TW, Butler VP Jr, Haber E. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. N Engl r Med 1982;307:1357-1362. 2. Wenger TL, Butler VP ]r, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. JACC 1985: 5:118A-123A. 3. Spiegel A, Marchlinski FE. Time course for reversal of digoxin toxicity with digoxin-specific antibody fragments. Am Heart J 1985;109:1397-1399. 4. Ferrier GR, Saunders JH, Mendez C. Celhdar mechanism for the generation of ventricular arrhythmias by acetyfstrophanthidin. Circ Res 1973; 32:600-609. 5. Hashimoto K, Kumura T, Kubota K. Study of the therapeutic and toxic effects of ouabain by simultaneous observations on the excised and bloodperfused sinoatrial node and papillary muscle preparations and the in situ heart of dogs. 1 Pharmacol Exp Ther 1973:186:463-471, 6. Rosen MR. Cellular electrophysiology of digitalis toxicity. JACC 1985;22A34A.
grammed stimulation, and serial studieswith procainamide, quinidine and phenytoin failed to suppress inducible ventricular tachycardia. She was treated with oral amiodarone (1,600mg/day for 1 week, 600 mg/day for 1 week, then 300 mg/day) and an automatic implantable cardioverter-defibrillator (AICD) (CPI). SubsequentHolter monitoring revealed normal sinus rhythm with occasional ventricular premature complexes. The patient was discharged with digoxin, 0.125 mg/day, and amiodarone, 300 mg/day. One month later she was readmitted with acute abdominal distress secondary to small bowel infarction. At Iaparotomy resection of the caecum and 18 inches of small bowel required creation of an iIeostomy. Five days after discharge she was readmitted with syncope and AICD discharge. She had bibasilar rales, a 2/6 systolic ejection murmur at the lower left sternal border with both third and fourth heart sounds. The serum potassium level was 6.0 mEq/liter, carbon dioxide 16 mmovliter, urea nitrogen 68 mg/dl and creatinine 2.0 mg/dl. Digoxin level was I.3 rig/ml. Arterial blood gas at room air revealed pH 7.3 Po2 84, PCOZ32, HCOQ16. Chest x-ray revealed cardiomegaly with appropriate positioning of the internal defibriilator leads. It appeared that dehydration, metabolic acidosis and hyperkalemia had developed, probably as a result of excessive ileostomy drainage. In addition, recurrent episodes of syncope in the hospital while undergoing telemetry were documented to be ventricular fibrillation, all converted by appropriate AICD discharges (Fig. I]. Considering the excessive ileostomy
FIGURE 1. Episode of ventrlcular fibrfllation successfully converted by internal automatic cardioverter-defibrillator (IACD) discharge.
1.5, 1986
Responseof Digoxin Toxic Atrial Tachycardia to Digoxin-Specific Fab Fragments JOSEPH R. DESANTOLA, MD FRANCIS E. MARCHLINSKI, MD
D
igoxin-specific antibody fragments have been used successfully to safely treat ventricular ectopic activity, ventricular tachycardia, ventricular fibrillation, severe sinus bradycardia and atrioventricular block precipitated by excess digoxin.1-3 These arrhythmias in general have been reported to respond within 30 minutes of administration of digoxin-specific Fab fragments. We describe the time course and electrocardiographic response of a patient with digoxin toxic atria1 tachycardia to digoxin-specific Fab fragments.
THE AMERICAN
JOURNAL
OF CARDIOLOGY
Volume 58
1109
fore completion of the antibody fragment infusion. During the 70 minutes after infusion, the tachycardia rate gradually slowed to 83 beats/min and the PR interval progressively shortened (Fig. 1). The tachycardia then terminated and sinus rhythm resumed. The serum potassium level decreased from 5.4 mEq/liter immediately before the infusion to 4.5 mEq/liter 4 hours after the infusion. No adverse effects were observed. In the US., the results of digoxin-specific Fab fragment administration have been described in 63 patients.1-3 No previously reported patient had atria1 tachycardia. We have shown the efficacy of the antibody in controlling the atria1 tachyarrhythmias associated with digitalis excess. The arrhythmia did not
A 60-year-old man with idiopathic dilated cardiomyopathy, ejection fraction of 33% and paroxysmal atrial fibrillation was admitted to the hospital for evaluation of cutaneous and oral ulcers. Medications on admission included digoxin, 0.25 mg/day, quinidine sulfate, 300 mg every 6 hours, and isosorbide dinitrate, 40 mg/day. Blood pressure was lOO/SO mm/Hg and pulse was 60 beats/min. Precordial examination was unremarkable. Blood urea nitrogen was 61 mg/dl and creatinine 3.8 mg/dl. The electrocardiogram showed normal sinus rhythm at a rate of 65 beats/min, rare ventricular premature complexes, left anterior hemiblock and a nonspecific intraventricular conduction delay. The patient’s medications were continued without altering the dosage. On the third hospital day, the patient complained of nausea and vomited. Systolic blood pressure was 80 mm Hg. The electrocardiogram showed atriai tachycardia at a rate of 260 beats/min with 1:~ atrioventricular conduction and periods of variable block. Laboratory studies included a serum digoxin level of 4.0 rig/ml, creatinine 3.7 mg/dl, calcium 8.7 mg/dl, magnesium 1.9 mg/dl and potassium 5.4 mEq/liter. Intradermal skin testing and an intravenous challenge were performed with a small dose of purified ovine digoxin-specific Fab fragments. The patient was then treated with an intravenous infusion of 240 mg of the Fab fragments administered over 15 minutes. The tachycardia rate began to slow just be-
From the Clinical Electrophysiology Laboratory, Hospital of the University of Pennsylvania, and the Cardiovascular Section, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania. This study was supported in part by grants from the American Heart Association, Southeastern Pennsylvania Chapter, Philadelphia, and grants HL28093 and HLO7346 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland. Manuscript received January 10,1986; revised manuscript received April 3,1986, accepted April 8, 1986.
FIGURE 1. Electrocardiographic response to digoxin-specific Fab fragments. Toppanel, atrial tachycardia at a rate of 160 beats/min before Fab infusions. Subsequent panels show gradual slowing of atrial rate and PR interval shortening after Fab fragment infusion. Eighty minutes after Fab fragment administration, normal sinus rhythm resumed as evidenced by the altered P-wave morphologic characteristics.
1110
BRIEF REPORTS
promptly terminate, but gradually slowed beginning immediately and continuing during the 80 minutes after digoxin-specific Fab fragment infusion before terminating abruptly. Our observations are consistent with reports on the time course for reversal of other electrocardiographic manifestations of digoxin toxicity using digoxin-specific Fab fragments, although the maximum effect at 80 minutes is somewhat longer than that noted when reversing bradyarrhythmias. Our observation also may have implications with respect to the mechanism for atria1 tachycardia. Slowing of tachycardia with reversal of the toxic effects of digoxin is consistent with either triggered activity or abnormal automatic@ as the arrhythmia mechanisma4-”
Sinus Arrest with Intravenous Amiodarone ENRICO P. VELTRI, MD PHILIP R. REID, MD
A miodarone is a benzofuran derivative with potent electrophysiologic effects on the impulse generation and conduction system of the heart.1 The effects of amiodarone on the sinus node, in particular, are well described.z*3Sinus arrest4 and sinoatrial block5 with oral therapy have been demonstrated; we describe a patient with acute sinus arrest after intravenous amiodarone therapy. A 63-year-old woman with idiopathic dilated cardiomyopathy and ventricular tachyarrhythmias was admitted becauseof syncope. Five months earlier she had out-of-hospital cardiac arrest due to ventricular fibrillation. Baseline electrophysiologic study revealed normal sinus node recovery time and sinoatrial conduction; AH and HV intervals were normal. Sustained ventricular tachycardia was induced using proFrom the Divisions of Cardiology, Departments of Medicine, The Johns Hopkins Medical Institutions and Sinai Hospital, Baltimore, Maryland. Manuscript received February 4, 1986; revised manuscript received May 22, 1986, accepted May 26, 1986.
References 1. Smith TW, Butler VP Jr, Haber E. Treatment of life-threatening digitalis intoxication with digoxin-specific Fab antibody fragments. N Engl r Med 1982;307:1357-1362. 2. Wenger TL, Butler VP ]r, Haber E, Smith TW. Treatment of 63 severely digitalis-toxic patients with digoxin-specific antibody fragments. JACC 1985: 5:118A-123A. 3. Spiegel A, Marchlinski FE. Time course for reversal of digoxin toxicity with digoxin-specific antibody fragments. Am Heart J 1985;109:1397-1399. 4. Ferrier GR, Saunders JH, Mendez C. Celhdar mechanism for the generation of ventricular arrhythmias by acetyfstrophanthidin. Circ Res 1973; 32:600-609. 5. Hashimoto K, Kumura T, Kubota K. Study of the therapeutic and toxic effects of ouabain by simultaneous observations on the excised and bloodperfused sinoatrial node and papillary muscle preparations and the in situ heart of dogs. 1 Pharmacol Exp Ther 1973:186:463-471, 6. Rosen MR. Cellular electrophysiology of digitalis toxicity. JACC 1985;22A34A.
grammed stimulation, and serial studieswith procainamide, quinidine and phenytoin failed to suppress inducible ventricular tachycardia. She was treated with oral amiodarone (1,600mg/day for 1 week, 600 mg/day for 1 week, then 300 mg/day) and an automatic implantable cardioverter-defibrillator (AICD) (CPI). SubsequentHolter monitoring revealed normal sinus rhythm with occasional ventricular premature complexes. The patient was discharged with digoxin, 0.125 mg/day, and amiodarone, 300 mg/day. One month later she was readmitted with acute abdominal distress secondary to small bowel infarction. At Iaparotomy resection of the caecum and 18 inches of small bowel required creation of an iIeostomy. Five days after discharge she was readmitted with syncope and AICD discharge. She had bibasilar rales, a 2/6 systolic ejection murmur at the lower left sternal border with both third and fourth heart sounds. The serum potassium level was 6.0 mEq/liter, carbon dioxide 16 mmovliter, urea nitrogen 68 mg/dl and creatinine 2.0 mg/dl. Digoxin level was I.3 rig/ml. Arterial blood gas at room air revealed pH 7.3 Po2 84, PCOZ32, HCOQ16. Chest x-ray revealed cardiomegaly with appropriate positioning of the internal defibriilator leads. It appeared that dehydration, metabolic acidosis and hyperkalemia had developed, probably as a result of excessive ileostomy drainage. In addition, recurrent episodes of syncope in the hospital while undergoing telemetry were documented to be ventricular fibrillation, all converted by appropriate AICD discharges (Fig. I]. Considering the excessive ileostomy
FIGURE 1. Episode of ventrlcular fibrfllation successfully converted by internal automatic cardioverter-defibrillator (IACD) discharge.