Sudden Therapy

Death Due to Ventricular in Familial Hypertrophic

David M. Gilligan, MRCPI, Constantinos and Celia M. Oakley, FRCP

Tachycardia During Cardiomyopathy

G. Missouris, MRCP, Malcolm

he potential modes of sudden death in hypertrophic cardiomyopathy (HC) can be broadly divided into those in which arrhythmia is the primary cause and those in which initial hemodynamic deterioration or ischemia are followed by secondary arrhythmia. Fortuitous electrocardiographic monitoring at the time of cardiac arrest may elucidate the mechanism responsible in individual patients and improve our understanding of sudden death in this condition. We report on 1 patient from a family with HC who died suddenly during amiodarone therapy and who was wearing a Holter monitor at the time of death. Death was due to primary ventricular tachycardia progressing to ventricular fibrillation.

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The family demonstrates dominant transmission of HC (Figure I). Case II 5 is the subject of this From Clinical Cardiology (Department of Medicine), Royal Postgraduate Medical School, Hammersmith Hospital, Du Cane Road, London, W12 ONN United Kingdom, and the Department of Medicine, Frimley Park Hospital, Frimley, Surrey, United Kingdom. Manuscript received March 6,199l; revised manuscript received June 10,1991, and accepted June 11.

Amiodarone

J. Boyd, FRCP,

report. She presented, at age 48 years, in 1979 with paroxysmal nocturnal dyspnea and angina (no syncope). Echocardiography showed asymmetric septal hypertrophy (septum 23 mm, posterior wall 14 mm) and systolic anterior motion of the mitral valve. She was treated with verapamil, 360 mg/day and oxprenolol, 60 mg/day. In 1988 the patient developed atrial$brillation. Ventricular rates up to 190 beatslmin were recorded on Holter monitoring but there was no ventricular arrhythmia. Amiodarone was given in a dose of 200 mg/day to attempt a pharmacologic conversion to sinus rhythm and verapamil and oxprenolol were reduced to 240 and 40 mg/day, respectively. Although atria1 fibrillation persisted, the ventricular rate was controlled and therefore amiodarone was continued. Oneyear later the doseof amiodarone was reduced to 100 mg/day after the development of keratopathy which affected her vision. Three weeks after reducing the dose, the patient was undergoing repeat Holter monitoring when she collapsed suddenly while standing in a shop. Cardiopulmonary resuscitation was be-

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FIGURE 1. Pedigree of a family with hyperbophic cardiomyopathy transmitted in an autosomal dominant pattern. Only first-degree relatives of the affected subjects are shown. Diagonal line threugh symbol = deceased. Patient’s ages at the time of death or at the present time, if alive, are shown in brackets below symbok; patient identification numbers are to the upper right of symbok Case I 2 is suspected of having had hypertrophii cardiomyopathy because she died suddenly at the age of 50 years, but prxmortem clinical data were not obtained and an autopsy was not performed.

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gun approximately 8 minutes after collapse by an ambulance team; however, resuscitation was unsuccessful. The Holter record (Figure 2) showed continuous atria1 fibrillation; a ventricular couplet was followed by 12 normal beats, then ventricular tachycardia developed and rapidly degenerated to ventricular fibrillation. The morphology of the ventricular tachycardia alternated, suggestive of torsades de pointes, but the appearances were also consistent with monomorphic ventricular tachycardia and intermittent fusion of atria1 fibrillation beats. There was no change in heart rate and no ST-segment depression preceding ventricular tachycardia. The average QTc interval was 480 ms. At autopsy, the heart was enlarged (515 g) with isolated left ventricular hypertrophy. There was moderate atheroma of the left anterior descending artery but no thrombus. Histologic examination revealed areas offibrosis and myocardial cell disarray. Two of the patient’s first-degree relatives were also found to have HC and one has died suddenly. Case II 4, the patient’s brother, presented at age 55 years in 1986 with symptomatic atrialjibrillation that reverted spontaneously to sinus rhythm. Investigations showed asymmetric septal hypertrophy (septum 22 mm, posterior wall 13 mm), no left ventricular outflow tract gradient, normal coronary arteries and infrequent, multiform ventricular extrasystales on 48-hour Holter monitoring. He remained in sinus rhythm and did not receive drug therapy. In 1988 he died suddenly, several minutes after loading goods

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into a lorry. Autopsy showed a hypertrophied left ventricle (heart weight 620 g) with areas of myocardial disarray and fibrosis. There was also moderate atheroma without thrombus in the coronary arteries and patchy, recent infarction in the posterior septum. On family screening his asymptomatic daughter, case III 2, was found to have asymmetric septal hypertrophy with a left ventricular outflow tract gradient of 80 mm Hg. She has no arrhythmia on Holter monitoring.

Although a number of cases of syncope in HC have been documented, only 3 previous cases of electrocardiographic monitoring at the time of cardiac arrest have been reported. The first report, in 1988,’ suggested that myocardial ischemia preceded the terminal ventricular arrhythmias in a 30-year-old man. Recently, in 30 survivors of cardiac arrest, the episode was documented in 22: in a 7-year-old boy, ventricular fibrillation was preceded by marked ST depression and in a 32-year-old man, polymorphic ventricular tachycardia occurred as the primary event. In our patient, sudden death was due to ventricular tachycardia progressing to ventricular fibrillation without evidence of preceding hemodynamic deterioration or myocardial ischemia. This report supports the assertion that sudden death in HC may be due to primary ventricular arrhythmia. Low-dose amiodarone did not prevent sudden death in this case,3 but is uncertain whether the drug was antiarrhythmic, ineffective or proarrhythmic. Amiodarone in a dose of 200 mg/day may have been suppressing ventricular arrhythmias until the dose was halved 3 weeks before death. Against this

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FtGURE 2. Contimmue ?-channel Hokr monitor record ing the recording. Panel l&03:45 shows atrial fibrillation v-r couplet -m, fdbwd by 12 normal beate lar tachycanlia merges into coarse ventricular fibrill@on.

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cardiomyopathy who died eWdenty durrate of 100 beats&in. At 12:04#1 a tachywdia. bI pand 12:04~17 WIltIiUl-

interpretation is the absence of ventricular arrhythmia before therapy and the long half-life of amiodarone which implies that serum levels may not have decreased significantly within 3 weeks4 A proarrhythmic effect of amiodarone has been associated with high-dose therapy and marked QTc prolongation4 and therefore seems unlikely in this case. However, recent electrophysiologic studies suggest that amiodarone may facilitate the induction of ventricular tachycardia in some patients with HC5 and this effect cannot be excluded. Of note, neither adult had prior ventricular tachycardia on Holter monitoring, an important risk factor for sudden death in HC3 In both cases myocardial fibrosis was prominent and may have been a substrate for ventricular arrhythmias. The significance of the mild coronary atheroma found in both patients is questionable. Although case II 4 did show evidence of recent, patchy myocardial infarction, infarction has also been described in HC in the absence of

significant coronary artery disease.6 Regardless of etiology, the presence of ischemic changes in this case suggests that the mechanism of sudden death may differ among patients with HC, even among members of the same family.

1. Nicod P, Polikar R, Peterson KL. Hypertrophic cardiomyopathy and sudden death. N Engl J Med 1988;318:1255-1257. 2. Fananapazir L, Epstein SE. Hemodynamic and electrophysiologic evaluation of patients with hypertrophic cardiomyopathy surviving cardiac arrest. Am J Cardiol 1991;67:280-287, 3. McKenna WJ, Oakley CM, Krikler DM, Goodwin JF. Improved survival with amiodarone in patients with hypertrophic cardiomyopathy and ventricular tachy cardia. Br Heart J 1985;53:412-416. 4. Rotmensch HH, Belhassen B. Amiodarone in the management of cardiac arrhythmias: current concepts. Med Clin North Am 1988;72:321-358. 5. Fananapazir L, Epstein SE. Value of electrophysiologic studies in hypertrophic cardiomyopathy treated with amiodarone. Am J Cardiol 1991;67:175-182. 6. Maron BJ, Epstein SE, Roberts WC. Hypertrophic cardiomyopathy and transmural myocardial infarction without significant atherosclerosis of the extramural coronary arteries. Am J Cardiol 1979;43:1086-1102.

Relation of Clinical and Angiographic Factors to Functional as Measured by the Duke Activity Status Index Charlotte L. Nelson, Robert M. Califf, MD,

James E. Herndon, PhD, and Mark A. Hlatky, MD

MS,

mprovement of patient functional status is an important goal in the therapy of cardiovascular disease. Given the pressures on the medical profession to restrain the growth of health care costs, credible documentation of improved functional capacity as a result of therapy is particularly important, especially if effects on “hard end points” such as death or myocardial infarction are difficult to demonstrate. Measurement of functional status inevitably includes a subjective component, so that most physicians consider it a “soft end point.” Indeed, traditional measures, such as the New York Heart Association classification, have considerable imprecision and interobserver variability. In an attempt to overcome some of these limitations, we recently described a new method of determining functional capacity of patients with cardiac disease.’ The Duke Activity Status Index (DASI) is a brief self-ad-

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From the Division of Cardiology, Department of Medicine, and the Division of Biometry, Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina. This study was supported by Research Grants HL-36587 and HL-17670 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland; Research Grants HS-05635 and HS-06503 from the Agency for Health Care Policy and Research, Hyattsville, Maryland; Research Grant LM-04613 from the National Library of Medicine, Bethesda, Maryland; and grants from the Andrew W. Mellon Foundation, New York, New York, and the Robert Wood Johnson Foundation, Princeton, New Jersey. Manuscript received August 16, 1990; revised manuscript received and accepted June 11, 199 1.

Daniel B. Mark,

MD,

MPH,

Capacity

David B. Pryor,

MD,

ministered questionnaire that gauges the patient’s ability to perform common activities and uses the responses in a weighted score that assessesoverall patient functional capacity. To determine if DASI varies in an appropriate fashion according to clinical factors known to influence patient functional status, this study examines the correlation of DASI with clinical factors in a large, independent group of patients. All patients undergoing cardiac catheterization at Duke University Medical Center from March 1,1986, through February 28, 1987, were screened for entry into a long-term study of the effects of coronary revascularization.2 Patients in stable clinical condition who were without prior coronary angioplasty or coronary bypass surgery were approached for informed consent and study enrollment. Patients who underwent coronary revascularization within 6 weeks of cardiac catheterization form the study cohort and are the basis of this report. Each patient completed a self-administered questionnaire to determine functional capacity as measured by DASI. Clinical and demographic information was collected using the computerized medical information system described previou~ly.~ Descriptive statistics were generated using the SAS software package. Simple linear regression and multiple linear regression were used to compare the effect of predefined clinical factors on functional capacity. BRIEF REPORTS

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