Amiodarone and sustained ventricular arrhythmias: Statistical evidence of drug effectiveness

Amiodarone and sustained ventricular arrhythmias: Statistical evidence of drug effectiveness Previous studies have shown that amiodarone prevents sustained ventricular arrhythmias in 77% to 93% of patients. To date, a study using statistical analysis to verify the drug’s effectiveness has not been reported. Amiodarone was given to 17 patients with drug refractory sustained ventricular arrhythmias. All patients had serious underlying heart disease including coronary artery disease (15 patients) or cardiomyopathy (two patients). Ten patients had angiographic evidence of a left ventricular aneurysm. All patients had left ventricular dysfunction. The mean left ventricular ejection fraction was 33%. In the 5.5 f 8.3 months prior to amiodarone, these 17 patients had documented sustained ventricular arrhythmias requiring countershock (41 episodes), overdrive pacing (four episodes), or intravenous drugs (three episodes). Amiodarone was given as a loading dose (1 gm/day for 10 days) and a maintenance dose (200 to 600 mg/day). During a follow-up period of 8.9 2 5.7 months, only eight episodes occurred requiring countershock (5) or overdrive pacing (2); one patient died suddenly. A statistical test constructed for this problem showed a significant (p > 0.001) reduced risk of experiencing a sustained ventricular arrhythmia after amiodarone. This statistical model confirms previous studies showing that amiodarone prevents sustained ventricular arrhythmias and prevents sudden cardiac death. (AM HEART J 110:371, 1985.)

Greg C. Flaker, M.D., Martin A. Alpert, M.D., Richard R. Webel, M.D., Michael A. Ruder, M.D., John F. Sanfelippo, M.D., and Robert K. Tsutakawa, Columbia,

Ph.D.

MO.

Ventricular fibrillation and sustained ventricular tachycardia are life-threatening tachyarrhythmias which usually occur in patients with severe underlying heart disease. Previous studies have documented the high recurrence rate and high mortality rate in these patients.‘m5 Antiarrhythmic agents such as procainamide, quinidine, disopyramide, phenytoin, lidocaine-like drugs, and beta blockers can control these tachyarrhythmias in 30% to 75% of patients, using ECG recording@ or programmed ventricular stimulationg-” to determine drug efficacy. Control of the ventricular arrhythmia by either method has resulted in improved patient surviva1.6-‘0 In contrast, these and other studies”“” have shown that patients with sustained ventricular tachyarrhythmias which are not controlled with antiarrhythmic agents have an extremely poor prog-

nosis. In these patients, experimental antiarrhythmic agents such as amiodarone have been used with initial reports of success. la-l7 In these studies, amiodarone was given to patients at high risk for developing a life-threatening ventricular arrhythmia. The effectiveness of amiodarone has been gauged by the prevention of symptomatic ventricular tachycardia or sudden cardiac death. Success rates have varied from 77 % to 93%, with differences explained by variations in patient population, length of follow-up, and amiodarone dosing schedules. To date, a study using statistical methods to evaluate amiodarone effectiveness has not been reported. We evaluated 17 patients with drug refractory sustained ventricular arrhythmia and compared the number of symptomatic episodes before and after amiodarone using a statistical method devised solely for this analysis. We report our findings here.

F-om Clinics.

METHODS

Rweived atcepted

the

Divlsim

of Cardiology,

for publication Apr. 2. 1985.

Dec.

Llniversity 10. 1981:

revision

of Missouri received

Hospital Feb.

and

19, 1985;

Reprint requests: Greg C. Flaker. M.D., Division of Cardiology, University of Missouri Hospital and Clinics. One Hospital Dr.. Columbia, MO 6”‘l”.

Patients. The medical records of all patients (67) receiving amiodarone at our institution were reviewed. To be eligible for this study, patients had to have at least one spontaneously occurring episode of sustained ventricular arrhythmia refractory to at least one antiarrhythmic drug. 371

372

Flaker

Table

I. Clinical and hemodynamic characteristics

Patient 1

I 8 9 10 11 12 13 14

15 16 17

Abbreviations: fraction;

American

Age/Sex

Disease

L VEF

M 69 F 67 F 51 M 75 M 51 M 71 M 12 M 53 F 64 M 78 F 61 M 70 M 80 M 67 M 52 F 62 F

CAD, p-MI, LV aneurysm CAD, p-MI, LV aneurysm CAD, p-MI, LV aneurysm CAD CAD, p-MI CAD, p-MI, LV aneurysm Cardiomyopathy CAD, p-MI, LV aneurysm CAD, p-MI CAD, p-MI, LV aneurysm CAD, p-MI, LV aneurysm CAD, p-MI, LV aneurysm CAD, p-MI Cardiomyopathy CAD CAD, p-MI, LV aneurysm CAD, MI, LV aneurysm

40% 38% 27% 38% 34%

54

2 3 4 5 6

ejection

et al.

CAD = coronary artery p-MI = post myocardial

disease; LVEF infarction.

= left

11% 43 $0 31%

39 $0 16% 40 Yz 28% 48% 33 r-b 40% 25% ventricular

A sustained ventricular arrhythmia was defined as ventricular fibrillation or ventricular tachycardia requiring counterstock, overdrive pacing, or intravenous drug administration for termination. In addition, all patients demonstrated evidence of a sustainedventricular arrhythmia which occurred in the absenceof antiarrhythmic drug therapy or metabolic abnormality such as hypoxia or hypokalemia. None of the episodesoccurred in conjunction with a transmural myocardial infarction. For purposes of this study, drug refractoriness was defined as either ventricular tachycardia (three or more beats in a row, greater than 120 bpm) which occurred during therapeutic levels of quinidine, procainamide, aprindine, or during maximally tolerated dosesof mexiletine. Drug refractoriness during electrophysiologic testing was defined as more than six beats of monomorphic ventricular tachycardia induced after intravenous or oral administration of an antiarrhythmic agent using the same stimulation protocol as the baseline study (seebelow). Study protocol. Seventeen patients fulfilled entry criteria for this study. All were hospitalized in anticipation of electrophysiologic study. Antiarrhythmic drugs (if prescribed) were stopped for at least 48 hours, during which cardiac monitoring took place. Digoxin and beta blockers, if usedfor heart failure or angina pectoris, were continued on the establishedtreatment regimen. Electrophysiologic studies were performed in 15 patients. Single and double extrastimuli were applied during sinus rhythm or following ventricular pacing at multiple cycle lengths (400 to 600 msec) from multiple sites in the right and left ventricle. The stimulus was 1.8 msec in duration at twice diastolic threshold, using a constant current source (Medtronics 5325 or Bloom programmable stimulator). If a reproducibly initiated sustained arrhythmia was induced, intravenousprocainamide (up to 1250mg), quinidine (700 mg), or aprindine (170 mg) was given and ventricular stimulation

August, 1985 Heart Journal

was repeated. Maximally tolerated oral mexiletine was also tested and programmed ventricular stimulation was repeated at least 5 days after a stable dosingschedulewas achieved. Two patients were included in this analysis without electrophysiologic testing. Both had a documented sustained ventricular arrhythmia in the absenceof antiarrhythmic drugs and with therapeutic levels of a conventional agent. Both patients were felt to require antiarrhythmic drug therapy and both fulfilled criteria for entry into this study. They received amiodarone without electrophysiologic study. Left ventricular function was assessedby contrast ventriculography at cardiac catheterization (14 patients) or by nuclear gated blood pool ventriculography (two patients). After informed consent, amiodaronewas given as 1000mg per day for 10 days followed by a maintenance doseof 200 to 600 mg per day. During the loading phase, previously demonstrated ineffective agents were continued and were then gradually withdrawn. The total number of episodesof sustained ventricular arrhythmias after 10 days of amiodarone (due to the delayed onset of action of amiodarone)were reviewed and compared to the number of episodesbefore amiodarone therapy. For statistical analysis,we devised a variation of Cochran’s test (see Appendix), which may serve as a statistical model for evaluating arrhythmic control in the future. RESULTS

Seventeen patients were included in this analysis, including 11 men and 6 women, with a mean age of 65 -t 9.9 years. Fifteen patients had coronary artery disease demonstrated by coronary angiography (>70% obstruction of one or more coronary arteries). Most had three-vessel coronary artery disease. Of these 15 patients, 13 had suffered a previous myocardial infarction. Ten had evidence of a left

ventricular aneurysm. The remaining two patients in the study had a cardiomyopathy with decreased systolic function (left ventricular ejection fraction below 55 % ) but no evidence of coronary artery disease. All 17 patients had evidence of left ventricular dysfunction. Table I illustrates the clinical and hemodynamic data. In order to rule out the possibility of a druginduced arrhythmia, all patients had evidence of a sustained ventricular arrhythmia in the absence of antiarrhythmic drug therapy. Table II illustrates that a sustained ventricular arrhythmia was documented in the absence of antiarrhythmic drug therapy, either as a spontaneous occurrence (13 patients) or induced during programmed stimulation (four patients). As noted, most patients had both a spontaneously occurring and an induced sustained arrhythmia.

Jolume

110

Number

2

Amiodarone

and sustained

ventricular

373

arrhythmias

‘Table II. Spontaneousand induced arrhythmias before and after antiarrhythmic drug therapy Pre antiarrhythmic

drug

_____

--.~ Patient

N~I.

Spontaneous arrhythmia Sustained Nonsustained Sustained

VT

Sustained VT

\‘T

Sustained

VT

Sustained

VT

VF Sustained VT Nonsustained VT VF

VF Sustained VT Sustained VT Nonsustained VT

Sustained

Sustained

VT

Sustained VT Nonsustained VT

Sustained Sustained

VT VT

VF Nonsustained VT Sustained VT Sustained VT VF Sustained VT VF

Nonsustained VT Sustained VT Sustained VT Sustained VT

VT

drug ~--

_.

js pontancous arrh?rth.mia

Induced arrhythmia

V’I

Post antiarrhythmic _._ --__-

Sustained Sustained Sustained

VT

Sustained Sustained Nonsustained Nonsustained Sustained Sustained

VT VT

VT

VT

-

~-

__-.. ~--.

ill~iUl~~‘d arrh vthmia

(quinidine*) (procainamide) (procainamidel

(quinidine) (quinidine) VT (quinidine) VT (mexiletine) VT (procainamide) VT (mexiletine)

Sustained Sustained Sustained Sustained Sustained Sustained Sustained

V’T (procainamide) VT imexiletine) VT \prncainamide) VT fmexiletine) VT fprocainamide) VT iprocainamide) VT iprocainamide)

Sustained

V’l’ ~pr~~cainamidei

Sustained Sustained

VT ~procainamide) VT iprocainamide)

Sustained Sustained

VT VT

SustainedVT (mexiletineand aprindine)

Abbreviations:

VF = ventricular

fibrillation;

twined VT = nonsustained ventricular *Antiarrhythmic drug in parentheses

Previous

antiarrhythmics.

VF

Sustained

Nonsustained VT (quinidine) Sustained VT (quinidine)

SustainedVT (quinidineand procainamide) VF (quinidine) VF (quinidine) Sustained VT (quinidine) VF (quinidine) Sustained VT (quinidine) Nonsustained VT (quinidine)

VT = sustained

ventricular

tachycardia

tachycardia (more than 3 beats of VT, self-terminating). refers to the drug used at the t.ime of the documented

Previous single antiar-

rhythmic drug therapy was ineffective in controlling these rhythm disturbances. A total of 15 spontaneous episodes of sustained arrhythmias occurred in 11 patients despite therapeutic levels of procainamide (8 to 20 bg/ml) or quinidine (2.5 to 5 pg/ml) or aprindine (1 to 2 rglml) during maximally tolerated doses of mexiletine. The remaining spontaneous episodes occurred either in the absence of antiarrhythmic therapy or without knowledge of drug levels at the time of arrhythmia. Drug refractoriness was also demonstrated during sequential electrophysiologic testing. Table II illustrates the type of spontaneous or induced ventricular arrhythmia which occurred before or after antiarrhythmic drug therapy. Twelve of the patients undergoing sequential electrophysiologic studies failed single drug attempts to control the rhythm disturbance; three patients failed combinations of drugs as listed. Ventricular arrhythmias. In the 5.5 4 8.3 months prior to amiodarone, these 1’7 patients experienced a total of 48 spontaneous, documented episodes of sustained ventricular arrhythmias requiring coun-

VF (mexiletinr Sustained VT (requiring

shock. overdrive

pacing

! procainamide) iprocainamide)

and aprindine imexiletine) w IV drug);

Nonsus-

arrhythmia.

tershock (41 episodes), overdrive pacing (four episodes), or intravenous drugs (three episodes) for termination. Thirty-six episodes were sustained, monomorphic ventricular tachycardia; 12 episodes were ventricular fibrillation. An average of 2.8 i- 1.9 spontaneous episodes were documented per patient. After amiodarone over a follow-up period of 8.9 +5.7 months, 76% of our patients had effective suppression of symptomatic ventricular arrhythmias. Only eight episodes of presumed sustained ventricular arrhythmias have occurred in four patients. A statistical test, which was newly constructed for this problem and is described in the appendix, showed a significant (p > 0.001) decline in the incidence rate following treatment. Table III illustrates the number and type of ventricular arrhythmias before and after amiodarone. Patient No. 7 died unexpectedly in his sleep 1 month after amiodarone was begun. Patient No. 12 developed documented ventricular tachycardia 1 month after amiodarone and was successfully resuscitated. He subsequently received an automatic implantable

374

Flaker et al.

Table

III. Number

American

and type of spontaneous Before

ventricular

August, ,485 Heart Journal

arrhythmia

amiodarvne

After

amiodarone --

Patient

no.

Arrhythmia

Sustained Sustained Sustained VF Sustained Sustained VF Sustained Sustained Sustained VF VF VF Sust.ained VF VF Sustained VF

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 Abbreviations:

VF = ventricular

fibrillation;

Episodes

VT VT VT

Months

3 3 3

VT VT VT VT VT

1

2 I

15 8 7

3 1

33 1

s 1

1

VT VT = ventricular

1

12 1

Sustained VT

1 2 1 3 I 1

4 3

0 2 0

Months 1” 7 19 11 10 12 I n

8 14

2 0

3 4 3

1

0

3

1

0 0 0

11 5 21

tachycardia.

Previous studies have shown that prevents sustained ventricular arrhyth-

model.

3 1 0

Sustained VT

DISCUSSION Statistical

Sustained VT Sudden death

1 2

defibrillator (AID). One month later he lost consciousness and received a jolt (observed by his wife), indicating an electrical discharge from the device. Additional antiarrhythmic therapy, previously demonstrated ineffective when used alone, was started and the patient remains symptom-free. Five other episodes have occurred in patients No. 6 and 10. Both patients have received additional antiarrhythmic therapy which had been previously judged ineffective when used alone. Both patients have also relieved patient-activated burst pacemakers which have been demonstrated to terminate spontaneous occurrences of their sustained ventricular tachycardias. Two of the remaining patients have died, one of intractable heart failure and one of cancer. Side effects. None of our 17 patients have had to stop taking amiodarone because of side effects. One patient experienced nausea associated with elevated liver function tests; this condition resolved with reduction of amiodarone dosage. A second patient experienced muscle weakness, requiring a decreased dose. A third patient developed symptomatic sinus bradycardia, requiring a permanent dual-chambered pacemaker. A fourth patient experienced nausea, a bitter taste in her mouth, and halo vision. Corneal opacities, common with amiodarone, were identified on slit lamp examination. All symptoms improved with a reduction in dosage.

amiodarone

Episodes

0 0 0 0 0

1

2 2

VT

Arrhythmia

mias in 77 5% to 93% of patients over an 8- to 16-month follow-up period. In our small series of 17 patients followed over 8.9 months, 76% have had good suppression of sustained ventricular arrhythmias. Our study differs from previous studies in that we compared the number of sustained events prior to amiodarone with the number of events after amiodarone. In doing so, each patient served as a control and a statistical model could be applied to determine the effectiveness of amiodarone. Our study demonstrates that the risk for developing a sustained ventricular arrhythmia is significantly reduced after amiodarone. Sustained arrhythmia. A very important part of our study was that a sustained arrhythmia-either induced or spontaneous-be documented in the absence of antiarrhythmic agents. In the evaluation of drug efficacy, baseline information in the drugfree state is essential. For example, a patient may be treated for premature ventricular contractions (PVC4 with quinidine. If torsade de pointes and ventricular fibrillation occur as a result of quinidine, appropriate therapy would be to discontinue quinidine. If another drug is substituted and no further episodes occur, the favorable effect could be due to discontinuation of quinidine or the addition of a new drug. Thirteen of our patients had at least one documented spontaneous cardiac arrest in the absence of antiarrhythmic drugs. In the remaining four patients, programmed ventricular stimulation with single or double extrastimuli resulted in a sustained ventricular arrhythmia.

Amiodaronc

Studies support the concept that an inducible sustained arrhythmia in the electrophysiology laboratory is an indication of an electrically unstable ventricle which requires antiarrhythmic therapy. Vandepol et al.ls induced sustained ventricular tachycardia in 52 patients with single or double extrastimuli from either right ventricular or left ventricular sites. All had documented sustained ventricular tachycardia clinically. Conversely, of 57 patients with sustained ventricular tachycardia occurring spontaneously, 52 had inducible sustained ventricular tachycardia. Consequently, inducibility of sustained ventricular tachycardia in the electrophysiology laboratory is thought to represent a sensitive and specific method for evaluating these arrhythmias. Although there may have been some episodes of drug-induced arrhythmias included in t.he pre-amiodarone episodes, all patients had at least one standard arrhythmia in the absence of antiarrhythmic drugs and as such clearly required therapy. Refractory arrhythmia. We also considered our patients drug refractory if they failed only single antiarrhythmic therapy. At least one previous study has suggested that if a single drug is ineffective, the likelihood that combination drug therapy will be effective is 10w.l~ There is also evidence that the lack of response to procainamide during electrophysiologic studies predicts lack of success to other conventional antiarrhythmic agents.2” Hence we felt justified in referring to our patients as refractory to therapy and proceeded to amiodarone. In addition, our investigation required a documented sustained ventricular arrhythmia for inclusion into the study. A number of patients have had syncope of unknown etiology with sustained ventricular tachycardia induced at electrophysiology study. We believe that these patients had ventricular tachycardia resulting in syncope, but they were not included in this analysis since we were comparing number of documented sustained events (not syncope) before and after amiodarone. In conclusion, our statistical model confirms previous studies showing that amiodarone prevents sustained ventricular arrhythmias and sudden cardiac death. APPENDIX

Observation on each of N subject begins with the occurrence of the ventricular arrhythmia and continues for variable lengths of time before and after treatment. The statistical question considered is whether the incidence of the arrhythmia decreases subsequent to treatment. We constructed a variation of a conditional test proposed by Cochran.21

and sustained

r)entric.ular

wr:l).ihmias

375

For the ith subject, let si denote the time of observation before treatment and ti the total time. For the same subject, let ri denote the frequency of events before treatment and n, the total frequency before and after treatment, whether neither count includes the initial ventricular arrhythmia. Assuming the ni events occur randomly over time ti, the distribution of the frequency of events (rJ is binomial with mean p, = ni(sJti) and variance (7.');= Il;(Si/tJ(l

-

Si/ti).

The null hypothesis H, to be tested is that the expected value of ri equals CLifor all i. The alternative hypothesis is that the expected value exceeds vu,for some i. The test statistic to be used is Z = (R - p)/cr R = where

N c i=l

ri =

N c i=l

$7 =

g, and

For large N, Z is approximately uted with mean 0 and variance conditionally on (ni, si, ti). This based on Liapounoffs theorem.” N = 17, R = 31 and p = 14.21 and Z = 6.22, which is highly significant less than LO-“.

Ii? i=l

i

normally distrib1, under H, and approximation is For the data, (TV= 7.2784. Thus with a p value of

REFERENCES

1. Williams C, Ellis LB: Ventricular tachycardba: An analysis oi thirty-six cases. Arch Intern Med 71:13$. 194:i. 2. Armbrust CA. Levine SA: Paroxysmal ventricular tachycardia: A study of one hundred and seven cases. Circulation 1:Z-i. 1950.

X Cobb LA, Baum KS, Alvarez H III, Schaffer WA: Resuscitation from out-of-hospital ventricular fibrillation: 1 yearh follow-up. Circulation 51 and 52tSuppI IIIkIII-P2R, 1975. 4. Liberthson RR, Nagel EL, Hirschman JC. Nussenfeld SR: Prehospital ventricular fibrillation. Prognosis and follow-up course. N Engl J Med 291:317, 1974. 5. Schaffer WA, Cobb LA: Recurrent ventricular fibrillation and mode of death in survivors of out-of-hospital ventricular fibrillation. N Engl J Med 293:259. 1975. 6. Myerburg RJ, Briese FW, Conde C, Mallon SM, Liberthson RR. Castellanos A: Long-term antiarrhythmic t,herapy in survivors of prehospital cardiac arrest. ,I QMA 238:2f,Ql. 1977. 7. Winkle RA, Alderman EL, Fitzgerald JM, Harrison I)C: Treatment of recurrent symptomatic ventriclllar tachycardia. Ann Intern Med 85:1, 1976. 8. Graboys TB, Lown B, Podrid PJ. Desilva K: Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs. Am .I Carcliol 50:437. 198’. 9. Horowitz LN. *Josephson ME, Farshidi A. Spielman SR, Michelson EL, Greenspan AM: Recurrent sItstained ventricular tachycardia. 3. Role of the electrophysiologic study in selection of antiarrhythmic regimens. Cirl,ulation 58:9%. 1978. 10. Mason .JW, Winkle RA: Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhvthmic drug therapy for returrent ventricular tachvcardia. C‘irculation 58:971. 19%

August.

Flaker

et al.

American

11. Swerdlow CD, Blum J, Winkle RA, Griffin JC, Ross DL, Mason JW: Decreased incidence of antiarrhythmic drug efficacy at electrophysiologic study associated with the use of a third extrastimulus. AM-HEART J 104:1004, 1982. 12. Ruskin JN, DiMarco JP, Garan H: Out-of-hospital cardiac arrest. Electrophysiologic observations and selection of longterm antiarrhythmic therapy. N Engl J Med 303:607, 1980. 13. Roy D. Waxman H, Kienzle MG, Buxton AE, Marchlinski FE. Josenhson ME: Clinical characteristics and long-term follbw-up* in 119 survivors of cardiac arrest: Relatyon to inducibility at electrophysiologic testing. Am J Cardiol 52:969, 1983. 14. Nademanee K, Singh BN, Cannom DS, Weiss d, Feld G, Stevenson WG: Control of sudden recurrent arrhythmia deaths: Role of amiodarone. AM HEART J 106:895, 1983. 15. Heger JJ, Prystowsky EN, Zipes DP: Clinical efficacy of amiodarone in treatment of recurrent ventricular tachycardia and ventricular fibrillation. AM HEART J 106:887. 1983. 16. Waxman HL, &oh WC, Marchlinksi FE, Buxton AE, Sadowski LM, Horowitz LN, Josephson ME, Kastor JA: Amiodarone for control of sustained ventricular tachycardia: Clinical and electrophysiologic effect in 51 patients. Am J Cardiol 50:1066, 1982.

Cardiac function in patients amiodarone therapy

Heart

1985 Journal

17. Morady F, Sauve MJ, Malone P, Shen EN, Schwartz AB, Bhandari A, Keung E, Sung RJ, Scheinman MM: Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation. Am .I Cardiol 52:975, 1983. 18. Vandepol CJ, Farshidi A, Spielman SR, Greenspan AM, Horowitz LN, Josephson ME: Incidence and clinical significance of induced ventricular tachycardia. Am ,J Cardiol 45:725, 1980. 19. Ross DL, Sze DY, Keefe DL, Swerdlow ED, Echt DS, Griffin JC, Winkle RA: Mason JW: Antiarrhythmic drug combinations in the treatment of ventricular tachycardia: Efficacy and electrophysiologic effects. Circulation 66:1205, 1982. 20. Waxman HL, Buxton AE, Sadowski LM, Josephson ME: The response to procainamide during electrophysiologic study for sustained ventricular tachyarrhythmias predicts the response to other medications. Circulation 67:30, 1983. 21. Cochran WG: The comparison of percentages in matched samples. Biometrika 37:256, 1950. 22. Cram& H: Mathematical methods of statistics. Princeton, N.J., 1946, Princeton University Press, p 215.

on chronic

Antiarrhythmic agents may depress cardiac contractility and worsen heart failure. Few data are available describing the chronic effects of amiodarone on myocardial function. To assess the effects of amiodarone on cardiac function, we studied 41 consecutive patients with first-pass or equilibrium radionuclide angiography prior to and 3 months after drug therapy was initiated. The mean heart rate, systolic blood pressure (BP), and diastolic BP were not significantly altered by treatment. The mean ejection fraction was 36% 2 19 (mean -t 1 SD) at the time of drug initiation and 36% k 17 3 months later (p < 0.05). Nineteen patients had an ejection fraction >30% and 16 had an ejection fraction <30%. The mean change in ejectjon fraction for these two subgroups showed no statistically significant difference, although a decrease in EF >lO% was seen in three patients (symptomatic in two), necessitating an increase in diuretic dose. No correlation between amiodarone dose and change in ejection fraction (r = -0.12, p > 0.05) was noted. There was no correlation between baseline ejection fraction and change in ejection fraction over this 3-month period (r = -0.36, p > 0.05). In summary, amiodarone does hot depress left ventricular function and as a result can be used safely in patients with mild to moderate impairment of left ventricular function. In patients with stable left ventricular function, serial tests of left ventricular function may not be necessary. (AM HEART J 110:376, 1985.)

Kenneth A. Ellenbogen, M.D., William G. O’Callaghan, M.B., M.R.C.P., Paul G. Colavita, M.D., Mark S. Smith, M.D., and Lawrence D. German,

M.D.

Durham, N. C.

From the Division of Cardiology, Department of Medicine, Duke University Medical Center. Received for publication Nov. 27, 1984; revision received Feb. 27, 1985; accepted Apr. 2,1985. Reprint requests: Kenneth A. Ellenbogen, M.D., P.O. Box 31237, Duke University Medical Center, Durham, NC 27710. 376

Many patients with ventricular tachycardia have chronic underlying heart disease. In these patients, ant&rhythmic agents may depress myocardial contractility and worsen heart failure.’ Although this phenomenon is best described for disopyramide,2-4