Influence of Left Ventricular Dysfunctlon on Flecainide Therapy

Transcription

1 JACC Vl. 9, N. I January 1987: Influence f Left Ventricular Dysfunctln n Flecainide Therapy ANGELO A. V. DE PAOLA, MD, LEONARD N. HOROWITZ, MD, FACC, JOEL MORGANROTH, MD, FACC, SHEILA SENIOR, RN, SCOTT R. SPIELMAN, MD, FACC, ALLAN M. GREENSPAN, MD, FACC, HAROLD R. KAY, FACC Philadelphia, Pennsylvania Seventy-six patients with ventricular tachyarrhythmias (40 sustained and 36 nnsustained) were treated with ral flecainide. Radinuclide left ventricular ejectin fractin was 30% r less in 33 patients and greater than 30% in 43 patients. Befre flecainide, cmpensated heart failure was present in 23 patients (ejectin fractin :S 30% in 15 and> 30% in 8). Flecainide mean dse was 150 mg twice daily and mean plasma cncentratin was 720 ng/ml. New r wrsened cngestive heart failure ccurred in seven patients n flecainide therapy, all with an ejectin fractin f hissthan 30%; six had a previus histry f cmpensated heart failure and f these, three died. Ejectin fractin was the nly independent variable that significantly influenced efficacyand tlerance f flecainide. After 1 year f therapy, efficacy and tlerance was 58% (25 f 43) in patients with an ejectin fractin greater than 30% and 12% (4 f 33) in patients with an ejectin fractin f 30% r less (p < 0.001). Thus, cngestive heart failure can ccur during flecainide therapy, particularly in patients with a previus histry f cngestive heart failure and ejectin fractin f less than 30%, and may particularly limit therapy in these patients. Clinical efficacy and tlerance were significantly lwer in patients with an ejectin fractin f less than 30%. (J Am Cll CardiI1987;9:163-8) Flecainide acetate is a benzamide cmpund with antiarrhythmic actin. Clinical studies have demnstrated its electrphysilgic prperties (1-3) and efficacy in supressing ventriculararrhythmias (4-8) and it has been placed in class IC f the Vaughn-Williams antiarrhythmic drug classificatin schema (9). In bth experimental animals () and man (II), flecainide has been reprted t exert mycardial depressant actin, but the imprtance f this finding fr the clinical use f ftecainide has nt been clearly defined. This study was undertaken t investigate the influence f left ventricular dysfunctin n the results f flecainide therapy in patients with refractry ventricular arrhythmias. Methds Study patients. The study ppulatin included 76 cnsecutive patients with ventricular tachycardia refractry t Frm the Divisin f Clinical Cardiac Electrphysilgy, Sudden Death Preventin Prgram and the Cmputer Center f the Likff Cardivascular Institute, Hahnemann University, Philadelphia, Pennsylvania. Dr. de Pala is the recipient f a Pst-Dctral Fellwship frm FAPESP (Federaca de Ampar e Pesquisa d Estad de Sa Paul), Sa Paul, Brasil. Manuscript received April 7, 1986; revised manuscript received July 16, 1986, accepted August 13, Address fr reprints: Lenard N. Hrwitz MD, Likff Cardivascular Institute, Hahnemann University and Hspital, Brad and Vine Streets, Philadelphia, Pennsylvania by the American Cllege f Cardilgy cnventinal antiarrhythmic agents used in therapeutic dses. Frty patients had sustained and 36 had nnsustained ventricular tachycardia. There were 65 men and II wmen, with ages ranging frm 30 t 78 years (mean 62 ± 9). Crnary artery disease was present in 52 (68%) patients and 36 had suffered a mycardial infarctin mre than 3 mnths befre enrllment in this study. The underlying heart disease in the remaining patients was idipathic cngestive r hypertrphic cardimypathy (19 patients) and valvular heart disease (3 patients). Tw patients had n identifiable rganic heart disease. Twenty-three patients had a histry f cngestive heart failure; f these II were in New Yrk Heart Assciatin (NYHA) class II and 12 were in class III r IV. Each patient was in a cmpensated state befre initiatin f flecainide therapy. Definitins. Ventricular tachycardia was defined as the presence f three r mre sequential ventricular cmplexes at a rate f greater than 0/min. If this arrhythmia was lnger than 30 secnds in duratin r resulted in cardivascular cllapse, it was defined as sustained. Efficacy was defined by either nninvasive r invasive techniques. Patients with nnsustained ventricular tachycardia were evaluated with nninvasive techniques (Hlter mnitring) and efficacy was defined as suppressin f 0% f ventricular tachycardia episdes, and greater than 75% reductin f the frequency f ventricular premature cm /87/$3.50

2 164 DE PAOLA ET AL. FLECAINIDE AND LEFT VENTRICULAR DYSFUNCTION JACC Vl. 9. N. I January 1987:163-8 plexes. In patients with sustained ventricular tachycardia, efficacy was defined in the electrphysilgic labratry as preventin f initiatin f sustained ventricular tachycardia (::; 15 cmplexes) in patients in whm sustained ventricular tachycardia had been inducible at baseline while they were receiving n antiarrhythmic therapy. Flecainide was cnsidered beneficial but nt effective in electrphysilgic testing if it prduced mre than a looms increase in the cycle length f ventricular tachycardia and eliminatin f severe symptms, even thugh it failed t prevent initiatin f sustained ventricular tachycardia. Our clinical experience has shwn that these criteria identify a regimen that reduces the severity f recurrences if they shuld ccur. Patients with efficacy r beneficial results were discharged n drug therapy. Clinical efficacy and tlerance were defined after I year f therapy as absence f either arrhythmic death, arrhythmia recurrence r severe txicity requiring drug discntinuatin. "Cngestive heart failure" was defined by the presence (in the past r during drug therapy) f clear clinical evidence f symptms and signs f cardiac failure (fr example, shrtness f breath n exertin r at rest, evidence f fluid retentin such as peripheral edema, pulmnary cngestin r jugular venus distensin) which required treatment with diuretics and intrpic r vasdilatr drugs, r bth, fr symptmatic relief. The functinal classificatin system f the NYHA was used (12). Treatment prtcl. During initiatin f therapy, each patient was hspitalized and placed n cntinuus telemetric electrcardigraphic mnitring. All antiarrhythmic drugs were discntinued fr at least five drug half-lives and clinical labratry evaluatin, 24 hur Hlter electrcardigraphic mnitring and radinuclide angigraphy were perfrmed in each patient. After written infrmed cnsent was btained, flecainide was initiated at a dse f 0 mg rally every 12 hurs. The dse was increased in 50 mg increments at 4 day intervals in-hspital t achieve efficacy. If either suppressin f ventriculartachycardia was nt achieved with a dse f 200 mg every 12 hurs r serius adverse effects ccurred, flecainide was discntinued. Patients were seen daily by ne f the investigatrs and questined abut symptms related t left ventricular functin. Radinuclide angigraphy was repeated after steady-state had been achieved n a flecainide dse which suppressed the ventricular tachycardia, r f 200 mg every 12 hurs. If flecainide was terminated prematurely because f txicity, radinuclide angigraphy may nt have been repeated. Fllw-up. Patients were seen in an arrhythmia research clinic by ne f the investigatrs 1 mnth after initiatin f flecainide and every 3 mnths thereafter. At each visit, patients were questined abut adverse experiences and cngestive heart failure symptms. They als underwent a clinical and labratry evaluatin, including a 24 hur Hlter mnitr recrding and measurement f randm plasma flecainide cncentratin. Statistical analysis. The results are presented as mean ± 1 SD. Statistical cmparisns were made using the Student t test; cntingency tables were evaluated by chi-square analysis and significance was defined as prbability(p) less than 0.05 using a tw-tailed analysis. Equality f efficacy and tlerance curves (patients n drug therapy) were analyzed using the Mantel-Cx and Breslw statistics. Lgistic regressin was used t select independent variables (age, sex, previus histry f cngestive heart failure, ejectin fractin, sustained r nnsustained ventricular arrhythmia and flecainide dsage and plasma levels), that culd influence efficacy and tlerance f flecainide. Results Baseline ejectin fractin. The baseline radinuclide ejectin fractin was 33 ± 13%. Thirty-three patients had an ejectin fractin f 30% r less and 43 had an ejectin fractin greater than 30%. Of the 36 patients with nnsustained ventricular tachycardia, 13 had an ejectin fractin f less than 30% and 23 f mre than 30%. Of 40 patients with sustained ventricular tachycardia, 20 had an ejectin fractin f less than 30% and 20 f mre than 30%. Of the 23 patients wh had a histry f cngestive heart failure befre initiatin f flecainide therapy, 15 had an ejectin fractin f less than 30% and 8 f mre than 30%. Effect f f1ecainide n ejectin fractin. Sixty-tw f the 76 patients were available fr radinuclide ejectin fractin measurement n steady-state flecainide at the maximally tlerated dse r at a dse that cntrlled their ventricular tachycardia. The mean ejectin fractin f these patients n flecainide was 32 ± 13% cmpared with 34 ± 13% at cntrl (p > 0.05). Distinct individual changes in ejectin fractin (abslute variatins> 5% between the preand pstdrug study) were seen in 22 patients. The ejectin fractin increased in 7 and decreased in 15 patients. At baseline, 4 f these 22 patients had an ejectin fractin f less than 30% and 18 f greater than 30% (p > 0.05) (Fig. 1). Effect f f1ecainide n patients with cngestive heart failure. N patient with an ejectin fractin greater than 30% develped wrsening r new nset f cngestive heart failure after the initiatin f flecainide therapy. Cnversely 7 f 33 (21%) patients with an ejectin fractin f 30% r less had new nset r wrsening f cngestive heart failure during f1ecainide therapy. Six f these patients had ptimally managed cngestive heart failure befre flecainide therapy and ne patient develped cngestive heart failure fr the first time after drug administratin (Fig. 2). Of 15 patients with an ejectin fractin f 30% r less and a histry f

3 JACC Vl. 9. N.1 January 1987:163-8 DE PAOLA ET AL. FLECAINIDE ANDLEFT VENTRICULAR DYSFUNCTION Figure l. Effect f flecainide n ejectin fractin. The baseline(b) ejectin fractin befre flecainide therapy and after achieving steady state plasma cncentratins at a dse that cntrlled ventricular tachycardia r 200 mgevery 12hurs (fr 7 days) are shwn. The graph n the left depicts data frm all patients studied, the center graph shws data frm patients whse ejectin fractin increased and the graph n the right frm patients whse ejectin fractin decreased. SO ~ c:.2 U u. ~ 30 c.2 ~ 20 W Days 8 7 Days > S% Increase 8 7 Day: > 5% Decrease heart failure, f1ecainide prduced wrsening f heart failure in 6 (40%). Twelve patients had class III r IV cngestive heart failure befre initiatin f f1ecainide therapy; seven patients had an ejectin fractin f 30% r less and five f greater than 30% (Table 1). On flecainide, five f these patients (all with ejectin fractin < 30%) had wrsening f cngestive heart failure and three died. Tw f these deaths were related t severe heart failure and refractry ventricular tachycardia during the in-hspital phase and ne patient died suddenly after hspital discharge. Wrsening cngestive heart failure in this patient had been successfully managed with an alteratin in the patient's heart failure regimen. Figure 2. Distributin f patients (pt) accrding t ejectin fractin, previus histry f heart failure and cngestive heart failure that develped while n flecainide therapy. The patients with a previus histry f cngestive heart fai lure are shwn in thesingle circles and thse wh develped new nset r wrsening f cngestive heart failure in the duble circle. The bttm rw indicates heart failure status during flecainide therapy. Only patients with an ejectin fractin (EF) less than 30% develped cngestive heart failure n flecainide therapy. Flecainide discntinuatin during in-hspital titratin. Flecainide was discntinued in 31 f the 76 patients during the shrt-term phase befre hspital discharge. In three patients, this discntinuatin was caused by heart failure n drug therapy (tw f these patients died with heart failure within 24 hurs after f1ecainide discntinuatin) and in ne patient it was related t a lethal prarrhythmic effect f the drug (incessant refractry ventricular tachycardia). F1ecainide was discntinued in 19 patients because f ineffectiveness. In 9 f these patients, lack f effectiveness was dcumented by spntaneus recurrences f previusly dcumented ventricular tachycardia befre hspital discharge and in the remaining, lack f efficacy was dcumented by Hlter mnitring (2 patients) r electrphysilgic studies (8 patients). In six patients, the discntinuatin was prmpted by changes in the surface electrcardigram Table 1. Cngestive Heart Failure During F1ecainide Therapy Patients With an EF f 30% r Less N. f CHF On Previus Functinal Class* Patients Flecainide Death I 18 I 0 II 8 I 0 III/IV I II III/IV Patients With an EF Over 30% *New Yrk Heart Assciati n functinal classificatin fr cnge stive heart failure (CHF). EF = ejectin fractin

4 166 DE PAOLA ET AL. FLECAINIDE ANDLEFf VENTRICULAR DYSFUNCTION JACC Vl. 9, N. I January 1987: (fur patients develped atriventricular blck, ne sinatrial pauses and ne junctinal rhythm). Flecainide was discntinued in tw patients because f nncardiac side effects. Lng-term respnse t fleeainide, After hspital discharge, 45 patients were fllwed up n flecainide. Befre flecainide therapy, the ejectin fractin was greater than 30% in 30 patients and 30% r less in 15; 13 had heart failure and 32 did nt. Within the first year, flecainide was discntinued in 16 patients, in nne because fheart failure. Three patients had recurrence f sustained ventricular tachycardia, five patients did nt maintain suppressin f ventricular tachycardia as determined by Hlter mnitring, tw patients develped atriventricular (AV) blck and tw nncardiac side effects. Fur patients died during fllw-up (three suddenly and ne because f acute mycardial infarctin). After 1 year f therapy, the efficacy and tlerance in these 45 patients discharged frm the hspital was 83% (25 f 30) in patients with an ejectin fractin greater than 30% and 26% (4 f 15) in patients with an ejectin fractin less than 30% (p < 0.001) (Fig. 3). Six (43%) f 13 patients with a histry f cngestive heart failure befre flecainide therapy and 23 (71%) f 32 withut heart failure were still n active therapy after 1 year (p > 0.05). Overall clinical efficacy and tlerance f flecainide related t ejectin fractin and cngestive heart failure status befre therapy. After 1 year f therapy, 29 (38%) f the riginal 76 patients entered int this trial remained n flecainide. Ejectin fractin was the nly independent Figure 3. Life-table analysis f results in 45 patients (30 with ejectin fractin> 30% and 15 -s 30%) discharged n ftecainide therapy. Efficacy and tlerance were significantly greater in patients with ejectin fractin (EF) greater than 30% when cmpared with patients with ejectin fractin less than 30%. The numbers in parentheses indicate the number f patients wh remained available fr analysis a " c: et Qj ~ > c: :.:; Qj.!ll ~ ~ <3 Cl (n=30) , I 'L '1...- L _ -:EF/.30% ---:EF>30% I.-~_~_.,...--.,._...-_~-.,._~_~~ Days p=o.ooi (n=25) (n=4) ẓ w (J N On Drug (Aller One Year) ::I~i :Iii".!.!-,!.~.:.:!,Illilliiliii::il:lllillill ::::::::: :: EF ('II.) 18 2 (11'11.) 2 (12'11.) (55'11.) 8 (53'11.) 7 (70'11.) Discussin.' I Figure 4. Clinical efficacy and tlerance (CET) f ftecainide as a functin f ejectin fractin (EF). Patients were gruped by ejectin fractin n the abscissa. After I year, clinical efficacy and tlerance were significantly greater in patients with ejectin fractin greater than 30% when cmpared with patients with ejectin fractin less than 30%. variable that significantly influenced efficacy and tlerance (p < 0.001) (Fig. 4). Clinical efficacy and tlerance (patients n drug therapy) was 58% (25 f 43) in patients with an ejectin fractin f mre than 30% and 12% (4 f 33) in patients with an ejectin fractin f less than 30% (p < 0.05). The clinical efficacy and tlerance was 26% (6 f 23) in patients wh had cngestive heart failure befre flecainide therapy and 43% (23 f 53) in patients wh did nt (p > 0.05) (Fig. 5). The acute respnse in hspital was greater in patients with nnsustained ventricular tachycardia than in thse with sustained ventricular tachycardia (72 versus 47%, p < 0.05). The chrnic respnse t flecainide in the tw patient grups was nt different (44 versus 32%, p = NS). Ejectin fractin during flecainide therapy. Flecainide acetate is a ptent suppressr f ventricular arrhythmias in humans. Clinical and experimental bservatins have demnstrated negative intrpic effects and a relatively lw incidence f new nset r wrsening f cngestive heart failure. Previus studies (11) demnstrated that intravenus flecainide in a dse f 1 r 2 mg/kg unifrmly prduced a significant but mild decrease in left ventricular ejectin frac-

5 JACC Vl. 9. N. I January 1987:163-8 DE PAOLA ET AL. FLECAINIDE AND LEFf VENTRICULAR DYSFUNCTION z 50.. w EF> 30 EF!. 30 NCHF CHF NSVT SUVT TOTAL N CEl CET ('I) Figure 5. Effect f ejectin fractin (EF), previus histry f cngestive heart failure (CHF) and type f ventricular tachycardia n acute and chrnic efficacy f flecainide therapy. On the abscissa, are patients gruped by ejectin fractin (EF > 30 and EF :5 30%). histry f heart failure and type f ventricular tachycardia (nnsustained [NSVTl r sustained [SUVT]). The slid bars represent the acute (in-hspital) efficacy and the hatched bars represent the chrnic (I year) efficacy. The number in each grup. and the number and percent ineach grupachieving clinical efficacy and tlerance (CET) are indicated. tin. Our patient grup did nt shw a signifi cant decrease in left ventricularejectin fractin. This difference is prbably due t the time f evaluatinand the lw initial ejectin fractin f ur patients. In additin, we were unable t measure ejectin fractin in thse patients wh develped severe cngestive heart failure during ftecainide therapy and thus the ptentially largestdecreases in ejectin fractin may have been missed. Cngestive heart failure during tlecainide therapy. In the present study, new nset f cngestive heart failure r wrsening f previusly stable cngestive heart failure ccurred in 7 f 76 patients. The incidence f newr wrsened heart failure after institutin f flecainide therapy was greater than that reprted (11) in a larger series f patients receiving ftecainide primarilyfr suppressin f ventricularpremature cmplexes. This difference is undubtedly due t ur patient ppulatin, which had a high incidence f left ventricular dysfunctin, previus histryf cngestive heart failureand serius ventricular arrhythmia. In the present study, we fund that the ptential fr wrsening cngestive heart failure was mst ntable in patients with an ejectin fractin less than 30% and severe cngestive heart failure. Because 40% f patients with an ejectin fractin f 30% r less and a histry f heart failure develped wrseningf cngestive heart failure, extreme cautin shuld be exercised in using flecainide in this grup f patients. Cmparisn with ther antiarrhythmic drugs. Little emphasis was placed n the ptential fr antiarrhythmic drugs t wrsen r prduce cngestive heart failure befre the intrductin f dispyramide ( 13). This latter agent was the first antiarrhythmic drug that was reprted t prduce a high incidence f new r wrsened cngestive heart failure. In fact, it was reprted t adversely effect left ventricular functin in as many as 50% f patients with a previus histry f heart failure. Pdrid et al. (13) reprted that dispyramide prduced cngestive heart failure in 16% f patients treated with the agent. In their series. cngestive heart failure generally remitted when the drug was discntinued. In ur series f high risk patients, ftecainide prduced wrseningf cngestiveheart failure in a smaller percentage f patients, althugh in sme the deteriratin f left ventricular functin was life-threatening. Rle f ejectin fractin in clinical efficacy f flecainide. One f the mst imprtant predictrs f utcme in patients with cardiac disease is left ventricular functin (14-19). The risk f sudden death is greatest in patients with reduced left ventricular functin, and a lw left ventricularejectin fractin is a sensitive indicatrf bth early and late mrtality after mycardial infarctin (20). Recent electrphysilgic studies have als suggested that the suppressin f inducible ventricular tachyarrhythmias by manycnventinal and investigatinal antiarrhythmic drugs is signifi cantly affected by the left ventricular ejectin fractin (21-23). Therefre, it is nt surprising that the clinical efficacy f ftecainide nted in the present study was significantly lwer in patients with a reduced ejectin fractin. The mst imprtant challenge fr antiarrhythmic drugs is t prevent sudden death in a well defined high risk grup f patients with ventriculararrhythmiasand severe left ventricular dysfunctin. The efficacy and tlerance f all antiarrhythmic drugs will prbably be lwer in these patients. Als, this stratificatin will be useful in cmparing the effect f antiarrhythmic drugs with the clinical utcme. Clinical implicatins. Flecainide is an antiarrhythmic drug that can be used in patients with ventriculartachycardia after careful in-hspital dse titratin. Such patients with a left ventricular ejectin fractin f 30% r less and a previus histry f cngestive heart failure are, hwever, at majr risk fr develping serius cardiac adverse effects frm antiarrhythmic drugs. Because it is infrequently effective and has cnsiderable txicity in patients with an ejectin fractin less than 30% and cngestiveheart failure, flecainide shuld nt generally be used in this grup. If flecainide is selected fr therapy in this grup, it shuld be initiated in-hspital with particular attentin paid t develpment f a new r wrsened cngestive heart failure, at

6 168 DE PAOLA ET AL. FLECAINIDE ANDLEFT' VENTRICULAR DYSFUNCTION ixcc Vl. 9. N. I January 1987:163-8 which time the drug shuld be discntinued r the dse adjusted. References I. Estes NAM, Garan H, Ruskin IN. Electrphysilgic prperties f flecainide acetate. Am J Cardil 1984;53:26B-29B. 2. Hellestrand KJ, Nathan AW, Bextn RS. Camm J. Electrphysilgic effects f flecainide acetate n sinus nde functin, anmalus atriventricular cnnectins, and pacemaker threshlds. Am J Cardil I984;53:30B-38B. 3. Mrganrth J. Hrwitz LN. Flecainide: its prarrhythmic effect and expected changes n the surface electrcardigram. Am J Cardil 1984;53:89B-94B. 4. Smani P. Antiarrhythmic effects f flecainide. Clin Pharmacl Ther 1980;27: Andersn JL, Lutz JR, Allisn SB. Electrphysilgic and antiarrhythmic effects f ral flecainide in patients with inducible ventricular tachycardia. J Am Cli Cardil 1983;2: Duff HJ, Rden DM, Maffucci RJ, et al. Suppressin f resistant ventricular arrhythmias by twice daily dsing with flecainide. Am J Cardil 1981;48: Duran D, Platia EV, Griffith LSC, Adhar G, Reid PR Suppressin f cmplex ventricular arrhythmias by ral f1ecainide. C1inPharmacl Ther 1982;32: Flecainide-Quinidine Research Grup. Flecainide versus quinidine fr treatment f chrnic ventricular arrhythmias. A multicenter clinical trial. Circulatin 1983;67: Mrganrth J. Premature ventricular cmplexes. Diagnsis and indicatins fr therapy. JAMA 1984;252: Kvam DC, Banitt EH, Schmid JR. Antiarrhythmic and electrphysilgic actins f flecainide in animal mdels. Am J Cardiel 1984;53:22B-25B. II. Jsephsn MA, Ikeda N, Singh BN. Effects f flecainide n ventricular functin: clinical and experimental crrelatins. Am J Cardil 1984;53:958-lB. 12. Criteria Cmmittee f the New Yrk Assciatin. Diseases f the Heart and Bld Vessels; Nmenclature and Criteria fr Diagnsis. 6th ed. Bstn: Little Brwn, 1964: Pdrid PJ, Scheneberg A, Lwn B. Cngestive heart failure caused by ral dispyramide. N Engl J Med 1980;302: Ruberman W, Weinblatt E, Gldberg, Frank CW, Chaudhary BS, Shapir S. Ventricular premature cmplexes and sudden death after mycardial infarctin. Circulatin 1981;64: Hultgren HN. Shettigar UR, Miller DC. Medical versus surgical treatment f unstable angina. Am J Cardil 1982;50: Vamauskas E, Olssn SB, Petersn CLE. Prspective randmised study f crnary artery bypass surgery in stable angina pectris. Lancet 1980;2: Krnenberg MW, Pedersn RW. Harstn WE, Brn ML. Bender HW, Friesinger GC. Left ventricular perfrmance after crnary bypass surgery. Predictin ffunctinal benefit. Ann Int M 1983;99: Murphy ML, Hultgren HN. Detre K. et al. Treatment f chrnic stable angina. A preliminary reprt f survival data f the randmized Veterans AdministratinCperativeStudy. N Engl J Med 1977;297: Cperative Unstable Angina Study Grup. Unstable angina pectris: natinal cperative study grup t cmpare medical and surgical therapy. I. Reprt f prtcl and patient ppulatin. Am J Cardil 1976;37: Bigger JT Jr, Crmilas J, Weld FM. Reiffel JA, Rlnitzky LM. Identificatin f high risk patients after mycardial infarctin: pinters fr management. In: Mrganrth J, Hrwitz LN, eds. Sudden Cardiac Death. New Yrk: Grune & Strattn, 1985: Meissner MD, Kay HR, Spielman SR, Greenspan AM, Kutalek SP, Hrwitz LN. Acute antiarrhythmic drug efficacy is independently related t left ventricular functin (abstr). J Am Cli Cardil 1986;7:130A. 22. Mrganrth J. Ambulatry ECG mnitring in the evaluatin f new antiarrhythmic drugs. Circulatin 1986;73(suppl 11): Spielman SR, Schwartz JS, McCarthy DM, et al. Predictrs f the success r failure f medical therapy in patients with chrnic recurrent sustained ventricular tachycardia : a discriminant analysis. J Am Cli Cardil 1983;1:401-8.