Evaluation of end points of serial drug testing in patients with sustained ventricular tachycardia after healing of acute myocardial infarction

Evaluation of End Points of Serial Drug testing in Patients With Sustained Ventricular tachycardia AfRer Healing of Acute Myocardial Infarction Stan 1. Wasilewski, MD, Kevin J. Ferrick, MD, James A. Roth, MD, Soo G. Kim, MD, and John D. Fisher, MD

94%, = NS), that o Ppatients

Serial electmphysiologic drug testing was used to uide antiarrhythmic thempy in a consecutive series 03 150 patients with clinical sustained ventricular tachycardia (VT) or cardiac arrest and inducible monomorphic VT. All patienk had coronary artery disease and a history of myocardial infarction. For patients with clinical sustained W, dr responders and paltial drug responders (VT 5103 by drug to rate <150 beak/min, with systolic blood pressure 30 mm Hg) had similar total mortality rates (2-year actuarial survival 100% and

which were statistically different from with dru ineffiiacy (2-year survival 67%). Partial drug respo IA! rs had high arrhythmia recurrence rates, similar to those of patients with d ineffica . For cardiac arrest survivors, the resulk Y o electrop x ysiologically guided drug testing did not rediet prognosis. Patients with a change in mode or VT induction during antiarrhythmic thempy had a favorable prognosis (no deaths during follow-up). (Am J Cardiol 1995;76: 1247-l 252)

lectrophysiologic testing has been established as a E means of identifying antiarrhythmic therapy that reduces the rate of arrhythmia recurrence and arrhythmic

The inclusion criteria were met by 150 patients. The patients ranged in age from 40 to 87 years (mean t- SD 65 +- 10 years). Eighty-one percent of the patients were men. Mean ejection fraction of the study patients was 34 +- 1.5%. The presenting arrhythmia was sustained VT in 79% of the study patients and cardiac arrest in 21%. All patients provided informed consent prior to electrophysiologic study. Ekctrophysidogic study protocok All patients underwent complete initial electrophysiologic study in the absence of antiarrhythmic agents. The ventricular stimulation protocol used has previously been reported.? Of particular note, the sequence for the basic stimulation protocol used at Montefiore is as follows: (I) single-, double-, and triple-programmed extrastimuli during sinus rhythm (sinus rhythm + I, 2, and 3 extrastimuli); (2) 1, 2. and 3 extrastimuli at a drive mte (VP1 + I, 2, and 3 extrastimuli) of 100 beats/min, or the lowest rate permitting 1: 1 capture without competition from conducted sinus beats or ventricular premature beats; (3) rapid ventricular pacing techniques using burst and incremental (ramp) pacing; (4) 1. 2, and 3 extrastimuli at a second drive rate (VP2 + I, 2. and 3 extrastimuli), 30 to 40 beats/min faster than VPI. Serial drug testing was performed using the multipolar catheter positioned through the subclavian vein during the initial electrophysiologic study. All study patients underwent repeat electrophysiologic study while they were taking discharge antiarrhythmic medications.

mortality in patients with sustained ventricular tachyarrhythmias.‘-I’ Since the first report of serial electrophysiologic drug testing for control of recurrent tdchyarrhythmias,* the standard end point of drug testing has been suppression of ventricular tachycardia (VT) induction. As VT remains inducible during antiarrhythmic therapy in most patients undergoing serial drug testing.” other end points of determining drug efficacy have been proposed, including the induction of a drug-slowed, welltolerated arrhythmia,“-‘” the need for a more aggressive stimulation protocol for arrhythmia induction,‘“.” and a reduction in the number of repetitive ventricular complexes induced by programmed stimulation.‘X.‘” We sought to determine if alternative end points of drug therapy could be identified that would be associated with outcomes similar to suppression of VT induction.

METHODS Study popukrtion: The study population consisted of a consecutive series of patients with healed myocardial infarctions and a clinical history of sustained VT or cardiac arrest, in whom sustained monomorphic VT was induced during baseline electrophysiologic study. Patients were excluded from analysis if they had implantable cardioverter-defibrillator placement or endocardial resection after electrophysiologic evaluation, or if they were given an antiarrhythmic regimen at discharge and not tested at follow-up study. From the Division of Cardiology, .Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York. Manuscript received April 24, 1995; revised manuscript received and accepted Scg tember 5. 1995. Address for reprints: Kevin J. Ferrick, MD. Arrhythmia Sewice Montefiore Medical Center, 1 1 1 East ‘i:Otf~ Street, Br:nx, Ne+, York 10467.

Definitions: SUSTAIWD

VENTKIC~LAR

TACHYCARDIA:

VT lasting 215 seconds or requiring intervention before that time: because of hemodynamic collapse. N~NSI:STAINEL~ VT:.NTRICIILAR'~AC~~YCAKI~IA: VT lasting ~15 seconds. DRLJG RESPONSE: Induction of 510 repetitive ventricular complexes with programmed ventricular stimulation when sustained VT was induced at baseline. For a patient to be considered a drug responder, the stimulation sequence had to be completed from the site of initial VT

Infarction

and

History

of Ventricular

TABLE II Infarction or Cardiac

Tachycardia

Comparison of Patients With Healed Myocardial Who Presented With Sustained Ventricular Tachycardia Arrest

Variable Number of potients Mean age (yr) Sex Men Women Mean LVEF (%) Presenting arrhythmia Sustained VT Cardiac arrest Baseline mean VT rate Discharge mean VT .rate

35 60

(23) zt 9*t

40 67*

(27)

27 (77) 8 123) 36* 17

35

(88)

36

sz 11

60 (80) 15 (20) 33 f 15

23 (66) 12 (34) 250 i 48rs -

34

(85) (151 * 48 17

62 (83) 13 (17) 229 zt 42 192i32

5

6 207 137i

11

112)

75 67

(50) * 9

l

i

p co.01 versus partial drug responders; ‘p
induction during drug testing, regardless of the induction mode that induced the initial tachycardia, except that isoproterenol was omitted unless required at baseline. PARTIAL DRUG RESPONSE: The induction of VT slowed by the drug to a rate ~150 beats/min associated with a systolic blood pressure of 290 mm Hg. The patient had to be free of angina, syncope, dizziness, or other symptoms suggestive of hemodynamic compromise during VT. To qualify as a partial drug response, the stimulation sequence had to be completed in the same fashion as for the drug response category. DRUG INEFFICACY: Induction of >I0 repetitive ventricular complexes with rate 2150 beats/min during drug testing. CHANGELNMODEOFVENTRICULARTACHYCARDlAAT INDUCTION: Patients whose VT was induced with nor-

mal sinus rhythm + 1, 2, and 3 extrastimuli or VP1 + 1, 2, and 3 at baseline study were prospectively defined as having more diflicult induction during antiarrhythmic therapy if sustained VT was not induced during the protocol through bursts and ramps, and was only induced during VP2 + 1, 2, or 3 extrastimuli while the patient was receiving discharge ant&rhythmic therapy. ARRHYTHMIA RECURRENCE: Documented sustained VT, cardiac arrest, or sudden cardiac death. SUDDEN DEATH: An unexpected, witnessed death occurring within 1 hour of the onset of symptoms, or an unwitnessed death during sleep. Fdlow-up: Patients were followed up in the Montefiore Arrhythmia Center and by their private physicians. Patient follow-up was analyzed for total mortality, sudden cardiac death, and arrhythmia recurrence. Patients were censored at the time of either alteration of their antiarrhythmic regimen or at the time of subsequent implantable cardioverter-defibrillator implantation because of arrhythmia recurrence. Statistical analysis: All data are presented as mean + SD. Life-table analysis was performed for the 3 clinical end points using the Kaplan-Meier technique. Survival curves were compared using the log rank test. A probability (p) value of co.05 was taken as significant. Patient subgroups were compared using Student’s t test (with 1248

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Discharge EP status Drug response Partial drug response Drug inefficacy Mean age (yr) Sex Men Women Mean LVEF p) Baseline mean VT rate Discharge mean VT rate Mean follow-up (mo) Follow-up end points Total mortality Sudden death Cardiac death Arrhythmia recurrence ‘p - 0.0001. Data are expressed EP = electrophyriologic

Sustained VT (n = 119)

Cardiac Arrest (n = 31)

23 (19) 34 (29) 62 (52) 66* 10

12 (39)

95 24 35* 221 172 36 36 12 29 48

(80) (20) 15 *47 zt 39 * 30

6 (191 13 (42) 64 i 8 27.(87) 31 255 178 27

(30) (10) (24) (40)

as mean * SD or number (x). study; other abbreviations as in Table

4 (131 f 13 i 37* * 39 zt 30 9 (29) 3 (10)

8 126) 6 (19)

I.

Bonferroni correction as appropriate) and chi-square tests, as appropriate.

RESULTS In all 150 study patients, sustained monomorphic VT was induced during control-state electrophysiologic study. The mean rate of the first sustained VT induced by programmed stimulation was 228 f 47 beats/min. All study patients underwent repeat electrophysiologic study performed while they were receiving discharge antiarrhythmic medication. At follow-up study, 35 patients (23%) met criteria for drug response. In the remaining 115 study patients, VT remained inducible during ant&rhythmic therapy. Of these, 40 patients (35%) met criteria for partial drug response. Despite undergoing 5.0 f 2.2 serial drug studies, the remaining 75 study patients (65%) failed to achieve either drug response or partial drug response criteria while following their discharge antiarrhythmic regimen. These 75 patients included (1) 51 patients with suppression of ventricular ectopy as assessed by 24-hour Holter monitoring (285% reductions in ventricular premature depolarizations and couplets, and 100% abolition of VT); (2) 7 patients who were discharged while receiving empiric amiodarone therapy; (3) 7 patients who had nonsustained VT induced during antiarrhythmic therapy which failed to meet drug-response criteria; (4) 6 patients who refused either further electrophysiologic-guided serial drug testing or implantable cardioverter-defibrillator implantation; and (5) 4 patients met none of these criteria and were discharged on antiarrhythmic therapy felt to be most effective on the basis of electrophysiologic study and Holter response. The clinical characteristics of the 3 patient subgroups are listed in Table I. Drug responders were younger than both partial drug responders and patients with drug inefficacy. Drug responders had faster monomorphic VT induced during baseline electrophysiologic study comDECEMBER

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pared with both partial drug responders and patients with drug inefficacy. There was no difference in clinical characteristics and discharge electrophysiologic status between patients who clinically presented with sustained VT and survivors of cardiac arrest, except that those with cardiac arrest had a significantly faster VT induced at baseline study (Table II). Patient follow-up: Patients were followed up for a mean of 34 + 30 months (range 0.4 to 119). The discharge antiarrhythmic regimen and follow-up end points for the study patients are listed in Table 111.Most patients were treated with class I agents, either as monotherapy, as part of combination therapy (class IA and IB), or together with a P-blocking agent (99 p;ltients, 66%). Amiodarone was given to 39 patients (26%). During follow-up, there were 45 deaths, 15 of which were classified as sudden cardiac deaths. The total mortality for all study patients was 15% at 1 year, 21% at 2 years, and 42% at 5 years. There was no overall difierence in survival between patients who clinically presented with sustained VT and those who survived a cardiac arrest. We analyzed the follow-up data separately for patients with sustained VT and those with cardiac arrest.

TABLE III Follow-Up Infarction Response

Status of Potients With Healed Myocordiol and History of Ventricular Tochycordio According to Antiorrhythmic Therapy Drug Responders (n = 35)

Variable Mean follow-up (mo) (mean * SD)

28

Discharge

f 25

+ class

I Follow-Up

Total mortality Sudden deoth Cardiac death Arrhythmia recurrence Values

are expressed

46

Antiorrhythmic

Class IA Class I6 Class IC Class IA + IB Class I + fi blocker p blocker Calcium channel blocker Amiodorone :;i$one 0

Partial Drug Responders (n = 40)

r~s number

Drug Inefficacy (n = 75)

* 33

31

*29

Medications

10 1 0 5 8 6 1 4

3 2 1: 7 0 0 8

9 3 2 22 11 1 0 17

0

:

64

End 7 1 6 3

to

Points

(201 (3) (171 (91

11 (28) 5 (13) 8 WI 19 (48)

of patients

27

(36)

9 (12) 23 (31) 32 (43)

VL).

Follow-up of patientswith sustainedventilcular tachy cardia: Sustained VT was the presenting arrhythmia’in

119 patients. Twenty-three patients (19%) were drug responders, 34 patients (29%) were partial drug responders, and 62 patients (52%) had drug inefficacy on their discharge regimen. The actuarial probability of survival for the 3 patient subgroups is shown in Figure I. There was no statistical difference in overall survival for drug responders and partial drug responders. There was a stdtistically significant difference in total mortality between patients with drug inefficacy for discharge therapy and both drug responders (p = 0.02) and partial drug responders (p = 0.03).

Survival free of sudden death is shown in Figure 2. Although drug responders had a low incidence of sudden death during follow-up, there was no statistically significant difference in survival free of sudden death between drug responders, partial drug responders, and patients with drug inefficacy. Arrhythmia-free survival is shown in Figure 3. There was a significant difference in survival free of arrhythmia recurrence between drug responders and both partial drug responders (p = 0.02) and patients with drug inefficacy (p = 0.0009). There was no difference in sur-

SUDDENDEATH SUSTAINED VT PATIENTS

TOTAL MORTALITY SUSTAINED VT PATIENTS 100

_ L .L.. --L---i l--L.-..-

DNg

Response

-‘.-

Drug

lnetficacy

- -

Partial

I

0 0

12

I

Drug Response I.

I.

24

38

1.1. 48

I 60

12

24

72

38

48

80

72

Months

Months FIGURE

2. Survival

free of sudden

cardiac

death

in 119

FWRE 1. Total survival for 119 paiients with healed myocurdial infarction who clinically presented with sustained ventricular tuch cardia (VT). palients who met M drug response and partial Ylrug response criteria had similar total suwival, which ‘ents who exhibited antiarrhythmic was better than ihat of drug inefficacy (p 405 F .

ARRHYTHMIAS

AND

CONDUCTION

DISTURBANCES/END

POINTS

OF SERIAL

DRUG

TESTING

1249

viva1 free of arrhythmia recurrence between partial drug responders and patients with drug inefficacy. Follow-up of patients surviving cardiac arrest: Thirtyone study patients were cardiac arrest survivors. All patients had monomorphic VT induced at baseline electrophysiologic study. Of these patients, 12 (39%) were drug responders, 6 (19%) were partial drug responders, and 13 (42%) had drug inefficacy of their discharge regimen. There was no difference in total mortality rates between these 3 subgroups (Figure 4). There was also no difierence in sudden death rates and arrhythmia recurrence rates. There were no differences in clinical characteristics among these subgroups of cardiac arrest survivors. Follow-up lar tachycardia

of patients induction:

with

change

in mode

of ventricu-

During follow-up electrophysiologic testing while patients were receiving antiarrhythmic medication as per discharge regimen, 115 patients failed to meet drug response criteria. Most of these patients (n = 105) had VT inducible with the same intensity of stimulation; however, IO patients had a change in the mode of VT induction during antiarrhythmic therapy. These 10 patients with more difticult VT induction had similar baseline clinical characteristics as the patients who had VT inducible with the same intensity of stimulation. One patient with a change in mode of VT induction met partial drug response criteria. During follow-up, no patient with a change in the mode of VT induction died. Of the 105 patients who had VT inducible with the same intensity of stimulation during antiarrhythmic therapy, there were 38 deaths (36%) and 14 sudden deaths (13%). The actuarial probability of survival is shown in Figure 5. There was a significant difference in total mortality between patients with a change in mode of VT induction and all patients who had VT inducible with the same intensity of stimulation ARRHYTHMIA SUSTAINED

RECURRENCE VT PATIENTS

(p = 0.01). There was no statistically significant difference in survival free from sudden death between these 2 groups (p = 0.13).

DISCUSSION Electrophysiologic testing is commonly used to guide antiarrhythmic drug therapy in patients with ventricular tachyarrhythmias. Because VT remains inducible during antiarrhythmic therapy in most patients undergoing serial drug testing,‘* we sought to determine if alternative end points of drug therapy could be identified that would be associated with clinical outcomes similar to suppression of VT induction. The study population consisted of a consecutive series of patients with healed myocardial infarction who presented with sustained VT or cardiac arrest. Only patients with sustained monomorphic VT induced during control-state electrophysiologic study were included in this analysis. Because it has been suggested”-*’ that clinical, anatomic, and electrophysiologic differences exist between survivors of cardiac arrest and patients who present with hemodynamically tolerated sustained VT, we analyzed follow-up data separately for patients with sustained VT and for those who survived cardiac arrest. In patients who presented with sustained VT, there was no difference in total mortality rates between drug responders and partial drug responders. Both of these subgroups had better survival rates when compared with patients who had drug inefficacy predicted by lack of response during discharge regimen therapy. However, arrhythmia recurrence rates of partial drug responders were similar to those of patients with drug ineflicacy; drug responders had a significantly lower rate of arrhythmia recurrence when compared with the other 2 subgroups. In contrast, there was no statistical difference in total mortality, sudden death, or arrhythmia recurrence rates between drug responders, partial drug responders, or patients with drug inetlicacy for patients who were car-

TOTAL MORTALITY CARDIAC ARREST PATIENTS

-

Drug Response

-.

- Drug lnefkacy

- 0 0

Partial Drqg Response

1.

I

12

24

*

1

36 Months

*

I

*

46

I,,

60

72

FIGURE 3. Survival free of arrh mia recurrence in 119 Patients with healed myocardia T infarction who clinically presented with sustained ventricular tachycardia M. Patients who met drug-response criteria had lower arrhythmia recurrence rates cornpored with both haI drug responders lp = 0.02) and Patients with drug I*Lacy (p = O.OOO9). Pa&al drug responders and Patients with drug in&cacy had similar high rates of arrhythmia recurrence.

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12

0

24

36 Months

46

60

FIGURE 4. Total survival for 31 Patients with healed myocardial infarction who clinically Presented with cardiac arrest. Then? was no difference in survival between antiarrhythmic drug drug re inx$$brG! drug =sponch and pahenb Gth

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72

disc arrest survivors. Drug responders tended to have a higher mortality than either partial drug responders or patients with drug inefficacy, although this did not reach statistical significance (p = 0.21, drug response vs drug ineticacy). These data confirm the conclusions of Wailer et al,‘” who demonstrated that patients who exhibit significant slowing of the rate of induced VT during antiarrhythmic therapy have similar total mortality and sudden death rates as patients in whom VT is rendered noninducible. They also found that patients with induction of a drugslowed VT have high rates of arrhythmia recurrence; however, the definition of beneficial response by Wailer et al was less stringent than our partial drug response criteria. When results for the 115 patients who had VT inducible during antiarrhythmic therapy in this study were analyzed using the Wailer et al definition of beneficial response, 39 patients met the criteria for beneficial response. Twenty-seven patients met both our definition of partial drug response and the Wailer et al beneficial response criteria. When we analyzed our data using the Wailer et al definition of beneficial response rather than our partial drug response definition, we found similar results. There are several major differences between this study and that of Wailer et al. I4 All of our study patients had a history of myocnrdial infarction and clinically presented with sustained VT or cardiac arrest, whereas 31% of their patients presented with syncope, nonsustained VT, or palpitations. In addition, all of our study patients had monomorphic VT induced at baseline electrophysiologic study, whereas 14% of their patients had ventricular fibrillation induced during baseline study. The mean length of our follow-up was 34 months. with 41 patients having follow-up of 24 years, whereas their mean length of follow-up was only 21 months, with only 6 patients having follow-up of 4 years. Moreover, 50% of their patients were treated with amiodarone. whereas TOTAL MORTALITY PATIENTS WITH CHANGE IN MODE OF VT INDUCTION VS. INDUCIBLE WITH SAME INTENSITY

-

100

only 26% of our study patients received amiodarone. Finally, Wailer et al did not analyze data for patients with cardiac arrest and those with sustained VT separately. Several studies have addressed whether changes in the mode of VT induction during antiarrhythmic therapy has prognostic signiticance with conflicting conclusions. McGovern et al’” reported that, for patients treated with amiodarone, patients in whom VT is no longer inducible or is more difficult to induce by programmed stimulation have a good prognosis. Naccarelli et a122reported that patients treated with amiodarone who required less aggressive stimulation techniques to induce VT had a high incidence of symptomatic recurrences of VT Horowitz et al” considered a reduction in the number of extrastimuli required to initiate VT to be a proarrhythmic response to antiarrhythmic therapy. Other workers’Q’ have reported that changes in the mode of VT induction do not have prognostic significance; however, these investigators have used difiering ventricular stimulation sequences, and detinitions of change in the mode of VT induction have varied. Previous studies have also reported day-to-day variability in the results of elecrrophysiolopic studies,-.75-Zx so that in some instances changes in the mode of VT induction may be due to limited reproducibility of programmed stimulation. The results of our study suggest that patients who meet our definition for change in mode of VT induction during antiarrhythmic therapy have a favorable prognosis. However. only 9% of patients with VT inducible during antiarrhythmic therapy met our criteria for change in mode of VT induction. Study )imilutions: This study is limited in that the total number of cardiac arrest survivors was small; therefore, conclusions regarding the value of electrophysiologically guided drug therapy for patients with cardiac arrest are limited. In addition, the study involved only medically treated patients. All patients treated with implantdble cardioverter-detibrillator implantation or endocardial resection were excluded; therefore, the relative benefits of antiarrhythmic therapy compared with implantable cardioverter-detibrillator therapy cannot be determined, although a recent study from our group suggests that the outcome of patients treated with implantable cardioverter-defibrillators may not ditl’er from that of patients whose treatment was guided by serial electrophysiologic drug testing.”

380 2

5 60 0 EP) 40

-

aii

-

7

20 0

12

Same intensity .- Harder

24

Induction

36

Months

48

60

72

FIGURE 5. Difference in total survival between 10 patients with a change in mode of ventricular tachycardia (VT) induction during anti;lMmic therapy and 105 bents &ho had ventricular tachycardia inducible with the same intensi of stimulation (p = 0.01). All patients had prior myocardial int rction.

ARRYYTHMIAS

AND

CONDIJCTIC~

1. Wellcna HJJ. Schuilenburg RM. Durrer D. Elecmical stmulation of the heart in p;titwnt~ with ventricular txhycmlia. C‘inubrion lY72:46:2lfe21Y. 2. Fisher JD, Cohen HL, Mehra R. Altshulrr H, Escher DJW. Furman S. Cartlinc pacing and pacernakcr\. Il. Serial elecrmphysiologic--ph~~dc~l~~ic testing for control ot recurrent txhyarrhythmia. Atn &urr J lY77;Y3:6584hhX. 3. Mawn JW. Winkle RA. Electrode catheter a~hyihmia induction in the selection imd assewnertt OS antinrrhythrnic drug therapy for rccurrcnt ventricul:u tachycardia. C‘itrxhrkw~ lY78:SX:Y71 985. 4. Ilorowit~ LN, Josephson ME, brshidi A. Spielman SR. Michelson EL, Gwnspan AM. Recurrent sustained ventricular tachycardia. 3. Role of the electn)physi~)logic sudy in selection of antianhythmic therapy. Cirwlrrrk,n IY7X;SX:YRh-YX7. 5. Kuskin JN. Dihlxco JP. Saran H. Out of’hwpiul cardiac arrest-+lrctrophysiologic observation and selection of Ior+term antiarrhythmic thempy. N 61g1 J Mrd l’)x0:303:607~l13. 6. Mwm JW, Winkle KA. .Accurq 01 the ventricular txhycardla induction study for prrdiuing long-wn, rtfirxy ant1 ~nrifk:~~~ (II anri;mhythmic drug>. N bIq~/ J Med IYXo:303: 107slU77. 7. H~ndltt DG. Benson IN’. Klein GJ. Priuker MR. Kriett JM. .An~ltrson KW. Pre-

D!SrURUANCC

S/“CND

POINTS

Ct

SERIAL DRLJG TESTING

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vention of recurrent sudden cardiac arrest: role of provocative electmpharmacologic testing. J Am CON Curdi~~l lY83;2:418-425. 8. Swerdlow CD. Winkle RA. Mason JW. Determinants of survival in patients with ventricular tachyarrhythmias. N Eizg/ J Mpd 1983;24:1436-1442. 9. Roy D, Waxman HL. Kienzle MC, Buxton AE, Marxhlinski FE, Josephson ME. Clinical characteristics and long-tern follow-up in I19 survivors of cardiac arrest: relation to inducibility at electmphysiologic testing. Am JCurdiol 1983;52:Y6%974. IO. Morady F. Scheinman MM. Hess DS, Sung RI. Shen E. Shapiro W. Electrophysiolqic testing in the management of survivors of out-of-hospital cardiac arrest.

Am J Curdiol

1983;51:85-KY.

11. Wilbur DJ, Garan use of electrophysiologic

Med

H, Finkdstein D, Ruskin testing in the prediction

1. Out-of-hospital cardiac arrest: of long-term outcome. N Eng/ J

1988;318:1%24.

12. Rae AP, Greenspan AM, Spielman SR, Sokoloff NM, Webb CR, Kay HR. Horowitz LN. Antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with coronary artery disetie as assessed by ehxtrophysiologic studies. Am

J Cordiul

1985;55:14Y4-14W.

13. Fisher ID, Fink D, Mates 1.4. Kim SG, Wasp L. Programmed stimulation and ventricular tachycardia therapy: benefits of partial as well a$ complete “cures.” (abstr) PACE lY82;6:13Y. 14. Wailer JJ, Kay HR. Spielman SR. Kutalek SP, Greenspan AM, Horowitz LN. Reduction in sudden death and total mortality by ant&rhythmic therapy evaluated by electrophyslologic drug testing: criteria of efficacy in patients with sustained ventricular tachyarrhythmia. JAm Co/l Cardiol 1987;10:83-89. 15. Handlin LR, Brodine WN. Gibbs H. Vacek JL. Slowing of ventricular tachy canlia as a pcxsible endpoint for serial drug testing at electrophysiologic study.

PACE

lY92:15:864-86Y.

16. McGovern B, Garan H, Malacoff RF, DiMarco JP. Grant G, Sellers D, Ruskin JN. Long tern] clinical outcome of ventricular tachycardia or fibrillation treated with amiodarone. Am J Cardi<~/ 1984;53: 1558-1563. 17. Horowitz LN, Greenspan AM, Rae AP, Kay HR, Spiehnan SR. Proarrhythmic responses during electrophysiologic testing. Am J Cardiol lY87;59:45w88. 18. Swerdlow C. Winkle R. Mason 3. Prognostic significance of the number of induced ventricular complexes during assessment of therapy for ventricular tachyarrbythntias. Circulariion 1983;68:4WO5. 19. Poole E, Mathisen T , Kudenchok PI, McAulty J, Swedlow C, Bardy GH. Green

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L. Long-term outcome in patients who survive out of hospital ventricular tibrillation and undergo electmphysiologic studies: evaluation by electrophysiologic subgroups. J Am Co11 Cardiol 1990;16:657-665. 20. Adhar GC. Larson LW, Bardy GH, Greene HL. Sustained ventricular an’hythmiss: differences between survivors of cardiac arrest and patients with recurrent sustained ventricular tachycardia. JAm Co/l Cardivl 1988;12:15Y-165. 21. The CASCADE Investigators. Randomized antianhythmic drug therapy in survivors of cardiac arrest (the CASCADE study). Am J Cardiol lYY3;72:280-287, 22. Naccatelli GV, Fineberg NS, Z&s DP. Heger 11, Duncan G, Prystowsky EN. Amiodarone: risk factors for recurrence of symptomatic ventricular tachycardia identified at electrophysiologic study. J Am Coil Cordial 1985;6:814-821. 23. Wellens HJJ, Bmgada P, Stevenson WG. Programmed electrical stimulation of the heart in patients with life-threatening ventricular arrhythmias: what is the significance of induced arrhythmias and what is the correct stimulation protocol? Circulation 1985;72: l-7. 24. Kim SG. Felder SD, Figura 1, Johnston DR, Mercando AD, Fisher JD. Prognostic value of the changes in the mode of ventricular tachycardia induction during therapy with amiodarone or amiodamne and a class IA antiarrhythmic agent. Am JCardio/ lY87;59:1314-1318. 25. McPherson CA, Rosenfeld LE. Batsford WP. Day-to-day reproducibility of responses to right ventricular programmed electrical stimulation: implications for serial drug testing. Am J Curdiul 1985:55:689-695. 26. Schoenfeld MH. McGovern 8, Charan H, Ruskin JN. Long-term reptuducibility of responses to programmed cardiac stimulation in spontaneous ventricular tachyarrhythmias. Am J Curdiol 1984;54:564-568. 27. Lombardi F, Stein J, Podrid PI. Graboys TB. Low” BP. Daily reproducibility of electrophysiologic test test&s in malignant ventricular arrhythmias. Am J Cardid 1986;57:9&101. 28. Ferrick KJ. Lute J, Miller S, Mercando AD, Kim SG. Roth JA. Fisher JD. Reproducibility of electmphysiologic testing during antiarrhythmic therapy for ventricular arrhythmias secondary to coronary artery disease. Am J Curdiol 1992;69:

1296-1299. 29. Choue CW, Kim SG, Fisher JD, Roth JA. Ferrick KJ, Brodman R. Frame R, Gross I, Furman S. Comparison of defibrillator therapy and other therapeutic modalities for sustained ventricular tachycardia or ventricular fibrillation associated with coronary artery discase. Am J Cardiol lY94;73:1075-1079.

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