Electrophysiologic study in the management of cardiac arrest survivors: A critical review

CURRlClJLlJM

NJ CARDlOl.OGY

Electrophysiologic st-udy in the cardiac arrest survivors: A critical

esment of review

Ying-Sui A. Lo, M.D., F.R.C.P.C., and Khiem P. V. Nguyen, M.D. Stanford, In the United States, fatalities from sudden cardiac death number more than 500,000 annually. Few cases of prehospital cardiac arrest are successfully resuscitated. The predominant rhythm documented at arrest is ventricular fibrillation (VF).‘s2 Coronary atherosclerosis with damaged myocardium constitutes the major electrophysiologic substrate for malignant ventricular tachyarrhythmias, and is responsible for most cardiac arresti.9-6 In the early 1970’s, there were three major studies dealing with survivors of prehospital cardiac arrest. Most patients studied did not have acute myocardial infarction. These studies quoted l-year mortality rates of about 30% .6-8Recent reports”, lo suggest that the outcome of cardiac arrest survivors has improved. Nevertheless, certain patient subgroups, particularly, survivors of non-infarct-related VF,8,* are at high risk for recurrent events. Also at risk are those with poor left ventricular function and ventricular arrhythmias, l1 two variables that are independently related to mortality risk.12 Since most victims of cardiac arrest suffer ventricular tachyarrhythmias terminally, successful prevention of such arrhythmias is important in the management of these patients. Noninvasive evaluation and monitoring of antiarrhythmic therapy have generally been unrewarding because clinical episodes of tachyarrhythmia may occur infrequently. Moreover, total suppression of ventricular ectopic activity does not necessarily imply freedom from risk of recurrent cardiac arrest. Intracardiac electrophysiologic study (EPS) has been used with considerable successfor treatment of recurrent sustained ventricular tachycardia (VT). Since then, results in this area have been extrapolated to management of survivors of cardiac arrest. This review discussesthe validity and limitations of EPS in the management of this patient population. From the Division of Cardiology, Stanford Medical Center. Received for publication Apr. 2, 1987; accepted May 12, 1987. Reprint requests: Ying-Sui A. Lo, M.D., Falk Cardiovascular Research Center, Division of Cardiology, Stanford Medical Center, Stanford, CA 94305.

596

VALUE

Calif.

OF ELECTROPHYSIOLOQlC

TESl?NG

Mechankms of ventricular tachycardia. Programmed ventricular stimulation contributed to understanding of mechanisms associated with VT.13-lsThe ability to initiate and/or terminate VT and phenomenon of entrainment support the idea that reentry underlies most VT.16~l7 Mapping of the VT activation sequence allows documentation of site of origin and sequence of activity.is, ln More importantly, serial testing of antiarrhythmic drug efficacy in a controlled environment is made possible by the ability to reproducibly induce tachyarrhythmia. EPS and

pharmacologic

therapy

in sustafned

VT.

EPS successfully identified medical regimens that prevented laboratory initiation of sustained VT in 30% to 70% of patients in whom VT was originally inducible without drugs. Recurrence rate was lower in patients treated with successful medical regimens than in those for whom no such regimen was found. Positive predictive value of EPS was reported to be between 70% and 90% over an B-month to 2-year follow-up.~-~~~~~ Persistent inducibility predicts an incidence of arrhythmic recurrence ranging from 36% to 90%. n-24*29Data from our institution also demonstrated that in patients with malignant ventricular tachyarrhythmias (VT/VF), one of the two strongest predictors of recurrent cardiac arrest was failure to suppress a previously inducible VT.9o EPS may also help demonstrate the hemodynamic consequences likely to accompany a recurrence of VT in patients who remain inducible despite antiarrhythmic therapy. It may also be useful in assessing the proarrhythmic potential of antiarrhythmic drugs.3*.32 Nonpharmacologic therapy. EPS is important in selection of patients for alternative nonpharmacologic therapy, e.g., automatic implantable cardioverter-defibrillator@ or electrocardiac surgery.“-% At present, all candidates for the automatic implantable defibrillator should probably be cardiac arrest survivors who have failed ant&rhythmic drugs tested in the electrophysiology laboratory.3B EPS is essential in intraoperative evaluation and subse-

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quent follow-up of patients with automatic implantable defibrillators.3s In cases of sustained VT associated with coronary artery disease and left ventricular aneurysm, pre- and intraoperative endocardial mapping have been helpful in guiding surgical ablation of arrhythmogenic foci.35,36 UNCERTAINTIES

PERTAINING

TO EPS

Favorable experience with EPS as a mode of therapy is largely based on empirical data. There are still many unresolved issues pertaining to programmed ventricular stimulation. Stimulation protocol. Lack of standard stimulation protocols has been and still is responsible for much confusion in the literature. The number of ventricular extrastimuli used is an important variable in stimulation protocols. Two extrastimuli can induce clinically-documented sustained VT in patients, with about 70 % to 95 % sensitivity.*ls 22p26v*o-42A third extrastimulus increases sensitivity at the expense of specificity. The tendency to initiate non-clinical forms of ventricular tachyarrhythmias including polymorphic VT or VF is increased with the use of three or four extrastimuli.43-46 The North American Society of Pacing and Electrophysiolo&7 recommended as being minimally acceptable a programmed stimulation protocol with 90% sensitivity for induction of VT in patients with prior myocardial infarction and VT. However, the panel did not comment on the optimal number of ventricular extrastimuli. Stimulation protocols commonly employ two right ventricular stimulation sites, Indications for left ventricular stimulation and the risk/benefit ratio of such stimulation are less clear.48-” At Stanford, two ventricular drive trains at cycle lengths of 600 and 400 msec are used; other laboratories use three different cycle lengths.51 Although the stimulating current is usually twice diastolic threshold, some investigators advocate using a current strength of 2 to 5 times diastolic threshold (or a minimum of 2 mA).52 On the other hand, there is a higher incidence of non-clinical arrhythmias initiated by stimulating currents of 10 mA.52*53 The optimal current strength is yet to be determined. Another unresolved issue is the specificity of the isoproterenol response.“eM Interpretation of induced rhythms. Interpretation of induced rhythms is based on retrospective validation, comparing induced arrhythmias with clinical arrhythmias. When the clinical arrhythmia is a monomorphic VT and the induced rhythm is sustained and has an identical rate and morphology, the latter is assumed to be clinically significant and serves as a target for suppression. However, the significance of induced nonsustained VT,43-46,57

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VT,437u,52,57-5g or VF is less clear.@, 45,52,53, b7,6o-62Data suggest that such induced arrhythmias may be nonspecific responses to aggressive programmed stimulation, especially in the absence of structural heart disease. On the other hand, “non-clinical” monomorphic VT induced in the electrophysiology laboratory may subsequently manifest clinically and cannot be completely ignored. 63 The induction of VT in patients with left ventricular aneurysm and no history of arrhythmia suggests that the substrate for VT is present and consideration may be given to prophylactic aneurysmectomy if the patient is a candidate for coronary artery bypass graft surgery.64 End points for suppression. Optimal end points for VT suppression have not been established. While it has been shown that increased VT cycle length (decrease in tachycardia rate) and improved hemodynamic stability without prevention of induction are acceptable end points,65 there are conflicting views.% Many physicians are uncomfortable with persistent inducibility and will often seek other modes of therapy such as electrocardiac surgery or the automatic implantable defibrillator. Another major question concerns the possible use of more aggressive protocols (additional ventricular extrastimuli) during drug evaluation than in the baseline study. A more rigorous test may produce a more effective drug regimen, but this theoretical advantage needs be weighed against a reduction in the number of potential regimens. The probability of exact reproducibility of arrhythmia induction is variable and may not be reliably high,66-68 supporting the contention that suppression of induction should be the primary method by which drug efficacy is determined, regardless of the number of extrastimuli required to initiate arrhythmias. On the other hand, reproducibility is somewhat dependent on the number of extrastimuli used.ffi,6E VT induction should be reproduced at least once before proceeding with electropharmacologic testing.6s Definition of noninducibility. In some laboratories, noninducibility is defined as two70 or five70B repetitive ventricular responses or fewer. In others, noninducibility is anything less than a sustained VT.71 At our institution, antiarrhythmic therapy that prevents initiation of VT to a maximum of 5 to 20 complexes results in a long-term recurrence rate of 10% or 1ess.72Induction of 15 or fewer complexes during drug testing may be regarded as a provisional definition of noninducibility, but a larger study is needed to validate this recommendation. polymorphic

Discordance between results of EPS and outcome. There are cases, as with amiodarone

clinical

therapy, where EPS may not be able to predict long-term

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clinical response to a drug. Suppression of previously induced VT in patients on amiodarone is predictive of freedom from VT recurrence. However, failure to suppress does not necessarily imply clinical inefficacy.73-77 Discordance between results of EPS and clinical outcome of this nature has also been described with other drugs such as propafenone.78 Though this is a controversial point, other studies have suggested that the results of EPS with amiodarone may be interpreted conventionally.7g~80 Intravenous vs oral drug administration. Antiarrhythmic agents may be given intravenously or orally. When given orally, certain metabolites that have potent electrophysiologic effects may be present.81-83 Myocardial levels of an intravenously administered drug may not reflect steady-state levels achieved during chronic oral therapy.@,% Dependence of successful ing heart disease. Coronary

VT induction

on underly-

artery disease has been the predominant type of heart disease in most studies on efficacy of EPS-guided therapy.2@s Conclusions may therefore not apply to patients with other types of structural heart disease in whom VT is less frequently induced.41s87 For instance, it has been shown that inducibility of sustained monomorphic VT in nonischemic dilated cardiomyopathies,41,87a88 hypertrophic cardiomyopathy,8g,90 and mitral valve prolapsegl may be less than 50%. However, it should be noted that the presenting arrhythmia is an important determinant of inducibility. In one study, patients with dilated cardiomyopathy presenting with sustained VT had a much higher incidence of inducible sustained monomorphic VT than previously reported.g2 Timing infarction.

of programmed

stimulation

after

myocardial

Infarct healing takes place during the first 3 to 5 months after myocardial infarction. Bhandari et aLg3 demonstrated that VT inducibility decreases by as much as 50% over the first few months after infarction in uncomplicated patients. Similar conclusions were reported by McComb et al.” Other studies have shown that a significant percentage (10% to 50% ) of uncomplicated postinfarction patients have inducible sustained monomorphic VT,g5-g7 but there was no correlation between inducibility and clinical outcome.g6-g8 This raises the issue that such induced arrhythmias may be nonspecific responses. On the other hand, two studieswvlm reported that programmed stimulation was useful in identifying patients at risk for malignant arrhythmias soon after myocardial infarction. Stevenson et aLlo suggested that the ability to induce sustained VT in patients with spontaneous sustained VT or VF after myocardial infarction

September 1987 Heart Journal

appeared independent of the interval between infarction and programmed stimulation. However, 50% of their VT patients were studied more than 6 months after infarction; 40% of VF patients were studied more than 8 weeks after infarction and the average interval from infarct to VF was 4.5 years in this group. It is possible that the substrate for VT had stabilized in these patients with remote myocardial infarction. Besides, serial EPS was not performed in this study. Hence the question of whether the electrophysiologic substrate changes over the first few months after myocardial infarction is not answered. Change in the electrophysiologic substrate and infarct healing should be taken into consideration in interpreting induced arrhythmias in patients studied soon after myocardial infarction. Cardiac arrest survivors with recent acute myocardial infarction fall into a grey zone, particularly if studied within the first few weeks after infarction. Factors responsible for cardiac arrest not addressed by EPS. EPS does not take into account factors such

as neural control of electrical stability of the hear&lo2 intracoronary platelet embolism,lo3, lo4 coronary lo5 and serum electrolyte abnormalities in the swm, pathogenesis of sudden cardiac arrest. Pathophysiologic conditions present at the time of arrest may not be present during EPS. It cannot be overemphasized that management of survivors of sudden cardiac arrest goes far beyond an electrophysiologic test. Mechanisms leading to sudden cardiac arrest vary, and it is unlikely that any single approach will answer all questions. In summary, there are still many unanswered questions pertaining to EPS. Awareness of these uncertainties is essential for a critical evaluation of the role of EPS in the management of cardiac arrest survivors. VALIDITY

OF EPS IN CARDIAC

ARREST

SURVIVORS

Infarct-related VF vs non-infarct-related VF. That VF was found to cause most cardiac arrests during the early hours after myocardial infarction implicates acute ischemia as the cause of arrhythmia. However, such arrhythmias can obviously also occur in the absence of acute ischemia. Early VF does not appear to alter long-term prognosis of patients, although there is a suggestion that the in-hospital mortality of such patients may be increased. Indeed, the prognosis of VF survivors who are discharged from the hospital is similar to that of patients with comparable infarcts who did not experience VF.l”, lo7 Relative to patients with infarct-related VF, those with non-infarct-related VF have a worse prognosis.6z8It is important, therefore, to be able to differ-

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entiate one condition from the other. Myocardial infarction is usually documented only in a minority of patients with VF. 6,* Cobb et aL6 documented new Q waves in only 16% of patients. Cardiac enzyme (LDH isoenzyme) elevation occurred in 45% of patients in this study. Disparity between incidence of Q waves and that of cardiac isoenzyme elevation may be explained by resuscitative efforts, including direct current shocks, or by development of non-Q wave infarction. Occasionally, it may be difficult to differentiate one from the other. It has been suggested that patients without Q wave evolution who have enzyme evidence of myocardial damage have a prognosis intermediate between those with Q wave infarctions and those without enzyme pattern of necrosis. However, this is not well documented.lo8 It should nevertheless be emphasized that it is the patient with non-infarct-related VF who would benefit most from EPS. Extrapolation of data from patients with sustained VT to VF survivors. Much of the literature on EPS-

guided therapy is in relation to evaluation and treatment of sustained VT, not VF. Is it then valid to extrapolate such data to victims of aborted cardiac arrest, in whom most documented rhythms at arrest are VF? Fortuitous observation of patients by Holter monitoring showed that the terminal event in cardiac arrest was usually a ventricular tachyarrhythmia-specifically, VF preceded by a period of increasingly frequent ventricular ectopic activity and/or VT.109-111 In most clinical circumstances, however, it is usually impossible to document whether VF is indeed preceded by VT; if such is the case, extrapolation of data from VT to VF patients is reasonable, although the two may not be identical. In a study comparing VT patients with those with noninfarct-related VF, Stevenson et al.l12 provided data showing no difference between the two groups in terms of left ventricular function. On the other hand, preliminary data from our institution suggest that in cardiac arrest survivors, patients with VT arrest have worse left ventricular function than those with VF arrest. A larger study is needed to resolve this issue. In the study by Stevenson et a1.,l12 sustained VT was initiated in 100% of patients with VT, and in 73 % of those with VF. In the VF group, induction of polymorphic VT or VF were more frequent; tachycardia cycle length of induced monomorphic VT was also shorter. Thus, there are demonstrable differences between VT and VF patients, although this distinction is of unknown clinical significance at this time.

Electrophysiologic

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599

Interpretation of induced arrhythmias. Despite claims that VF initiated in the electrophysiology laboratory may be a nonspecific response, the significance in patients with documented VF at arrest is uncertain. That VF can be induced in patients without spontaneous tachyarrhythmias does not necessarily imply that induction of VF in patients with VT or fibrillation is nonspecific. It is probably appropriate to treat induced VF as a clinical arrhythmia in survivors of cardiac arrest, although there is no rigorous proof that this is the correct approach. In a preliminary report, Freedman et al.112aanalyzed 183 cardiac arrest survivors and the prognosis of those with inducible ventricular tachyarrhythmias at baseline EPS appeared to be similar irrespective of the nature of the arrhythmia induced (VF vs sustained VT vs nonsustained VT). When the rhythm at arrest is not documented, what constitutes a clinically relevant rhythm in the electrophysiology laboratory? At this juncture, there is no good answer to this question. Most would agree that the most relevant rhythm induced in the electrophysiology laboratory is monomorphic VT, but polymorphic VT or VF cannot be ignored. CLINICAL THERAPY

STUDIES ON EFFICACY OF EPS-GUIDED IN CARDIAC ARREST SURVIVORS

Data from centers experienced in EPS are disbelow 123 . 70,71. 113.122,122a. Representative results are listed in Table I. Prognosis of patients in whom no VT was induced at baseline study is shown in Table II. Despite nonuniform methodologies, these studies provided important empirical data on the usefulness of EPS in preventing recurrent cardiac arrest. Suppression of inducible VT by antiarrhythmic drugs, electrocardiac surgery, and/or coronary artery bypass graft surgery were correlated with a good prognosis at four centers over relatively shortterm follow-up (2 years).‘13*114*118,11sIn their most recent report, Kehoe et a1.115analyzed 139 survivors of non-infact-related VF. Using the stepwise Cox proportional hazard model, they concluded that persistent inducibility at predischarge programmed stimulation was most predictive of arrhythmic recurrence. This is in general agreement with resulta from our institution with respect to treating sustained ventricular tachyarrhythmias.30 This observation is further confirmed by the Massachusetts General Hospital series, where persistently inducible VT was a significant predictor of recurrent arrhythmic events.lzO However, at other centers,71s 117 prognosis in patients with suppressible VT was not as favorable. Noninducibility. At some centers, initial noninducicussed

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Lo and Nguyen

Table

I. Clinical

American

outcomes

with EPS-guided

therapy

Successful suppression of inducible VTIVF

Study

Roy et al.‘]

R VT/VF (mean follow-up)

41 (AAD* f ES +

6 (18 mo)

Kehoe et a1.‘14 Morady et al.lL7

21 (AAD k ES f CABG) 16 (AAD*/ES) 9 (AAD)*

1(18 * 8 mo) 0 (14 mo) 3 (20 k 7 mo)

Ruskin et al.‘O Ruskin et al.‘l9 Skale et al.“*

19 (AAD) 36 (AAD) 12 (AAD) 2 (amiodarone)

0 (15 mo) 2 (18 mo) 0 (22 mo)

Eldar et a1.122a

10 (AAD)

3 (25 mo)

RVT/VF = recurrent ventricular tachycardia surgery = coronary artery bypass graft surgery

Table

II. Clinical Study

Roy et al.”

Benditt et al.“’ Kehoe et al.“’ Zheutlin et al.“’

Skale et al.“* Ruskin et al.‘O Morady et al.*21 Eldar et al.“‘”

outcomes

22 (Am)* 7 (surgery) 18 (no AAD) 3 (AAD) 1 (no rx) 16 (no AAD) 13 (surgery + other rx) 17 (other rx) 2 (no rx) 15 (AAD or amiodarone) 14 (no AAD) 14 (surgery *AAD* other rx) 13 (empiric) 10 (amiodarone) 3 (no AAD)

patients

RVTIVF (mean follow-up) 15 (20 mo)

2 (lo-13 mo) 0 (14 mo) 1 (24.5 + 15 mo)

2 (22 mo) 0 (15 mo) 1 (26 f 15 mo) 9 (25 k 21 mo)

RVTNT = recurrent ventricular tachycardia or fibrillation; AAD = antiarrhythmic drugs; AAD* = antiarrhythmic drugs excluding amiodarone; Other rx = other medical therapy; ES = cardiac electrosurgery; surgery = coronary artery bypass graft surgery and/or aneurysmectomy.

bility at baseline EPS carried good short-term (14 to On the other 20 months) prognosis. 70,114,116,118,120-122 hand, in the series by Roy et al.,71 incidence of recurrent cardiac arrest over a mean follow-up of 20 months in the “noninducible” group was 30% to 40% ; treatment of noninducible patients in this group did not affect final outcome. The authors hypothesized that lack of inducibility and hence inability to assess drug effects contributed to the

suppression VTfVF

R VTIVF (mean follow-up)

(amiodarone) (AAD)* 5 (AAD + ES + surgery) 9 (AAD)* 23 (amiodarone) 2 (surgery) 6 (AAD) 11 (AAD) 22 (amiodarone/AAD) 2 (surgery + ES) 3 (AAD) 34 (amiodarone) 9 (AAD-modified VT)

or fibrillation; AAD = antiarrhythmic drugs; AAD* and/or aneurysmectomy; ES = cardiac electrosurgery.

in “noninducible”

Number patients

Unsuccessful of inducible 12 15

surgery)

Benditt et a1.1L3

September 1987 Heart Journal

= antiarrhythmic

1 (16 mo)

4 (16 mo) 2 (2 wks-25 mo) 7 (9.1 I! 5.2 mo) 2 (18 it 14 mo) 1 (12 mo) 3 (<6 mo) 4 (15 mo) 8 (22 mo) 0 (22 mo) 2 (22 mo) 10 (25 mo) 5 drugs

excluding

amiodarone;

high recurrent cardiac arrest rate. In this series, the description “noninducible” applied to patients without inducible sustained VT. In some studies, no more than two repetitive ventricular responses were allowed when defining a patient as “noninducible” in others, the definition required the absence of inducible VT, sustained or nonsustained. It is likely that the “noninducible” group in the series of Roy et al. was inherently more prone to VT than those in other series, because their definition of “noninducible” systematically included many patients who would have been categorized as “inducible” by other investigators. Timing of programmed stimulation after arrest. In a prospective study of 73 cardiac arrest survivors, prior myocardial infarction was the only independent predictor of induced sustained VT. The length of time between arrest and EPS did not affect probability of inducing VT; this was true up to a period of 6 months after arrest.lz3 Methodologic shortcomings. Although experience with EPS-guided therapy for cardiac arrest survivors was generally favorable, these studies had several methodologic deficiencies. Heterogeneity of patient populations was a major shortcoming, because prognosis varies from one type of heart disease to another. The rate of VT recurrence is also inherently different. Applying results of EPS-guided therapy to a heterogeneous population is therefore problematic. Second, cardiac arrest due to non-Q wave myocardial infarction in some patients could not be excluded. For example, diagnosis of acute myocardial infarction was based solely on Q wave evolution in one study,‘O and criteria for

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excluding acute myocardial infarction were not specified in another. 11’ Third, stimulation protocols were not uniform. Some investigators resorted to a more aggressive protocol as needed71v”3,117 others limited the protocol to two extrastimuli. Left ventricular stimulation and/or isoproterenol were not employed in all studies. Fourth, definitions of sustained vs nonsustained VT varied. Several studies70p113,117*118did not separate sustained from nonsustained VT with respect to analysis of treatment results. Different investigators attached varying degrees of importance to each individual form of arrhythmia. End points for induction or aggressiveness of stimulation during baseline study and drug testing were not uniform in these studies. In the series of Roy et al.,71 the goal was prevention of previously inducible sustained VT, Skale et al.“* and Morady et al.l17 called for total suppression of previously inducible VT (nonsustained and sustained). Moreover, failure to risk stratify patients (e.g., on the basis of left ventricular function, coronary anatomy, or number of cardiac arrest episodes) resulted in data that are difficult to interpret. Finally, lack of a consistent approach to therapy in all these studies precludes any definitive conclusions regarding the efficacy of EPS-guided therapy. It is not easy to design and implement a satisfactory yet practical study to assess the efficacy of EPS in the management of survivors of cardiac arrest. Nevertheless, an appropriate protocol should include a relatively homogeneous patient population; specifically, patients with coronary artery disease should not be mixed with those with cardiomyopathy. Borderline cases where acute myocardial infarction cannot be completely excluded should not be included. Definition of inducibility or noninducibility should be standardized. Stratification according to important risk factors such as extent of coronary artery disease, ejection fraction, age, and probability of response to electropharmacologic therapy may also be helpful in providing the groundwork for meaningful analysis. Indeed, two studies28”*86 suggest that patients can be classified as having high, intermediate, or low probabilities of responding to electropharmacologic testing. NONINVASIVE

TECHNIQUES

VS EPS

EPS and noninvasive methods should not be regarded as mutually exclusive approaches to management of cardiac arrest survivors; they are in some ways complementary. *24-126EPS is necessary in patients with infrequent ventricular arrhythmia during Holter monitoring. On the other hand, clinicians may depend on noninvasive methods to guide

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antiarrhythmic therapy in patients with no inducible VT. A recent advance in noninvasive methods has been the advent of signal averaging of the surface ECG,126a,126bwhich appears to be a promising test for identification of patients at risk for arrhythmic events after myocardial infarction. ROLE OF EPS IN SPECIFIC

DISEASE

ENTITIES

Cardiomyopathy. Although vasodilator therapy reduces mortality in dilated cardiomyopathy, antiarrhythmic therapy may or may not decrease the incidence of sudden death. Preliminary data from our own institution127 and elsewheres8*s2 suggest that EPS-guided therapy can be helpful. Ventricular arrhythmias in hypertrophic cardiomyopathy are associated with an increased risk of sudden death. However, the clinical utility of inducible arrhythmias is unclear,89*9o and little definitive data are available with respect to the efficacy of electropharmacologic testing in such patients.12g 12s Bradyarrhythmias-sinus grade atrioventricular

node dysfunction and highblock. When diagnosis of

bradyarrhythmias is not apparent by electrocardiography, sinus node recovery, sinoatrial conduction, and atrioventricular conduction times can be measured. Decisions regarding pacemaker implantation may then be made. Implantation of a pacemaker should be strongly considered in survivors of sudden cardiac death with neither documented arrhythmias at arrest nor inducible tachyarrhythmias, but who have marked sinus node and/or atrioventricular conduction disturbances. It should be emphasized, however, that Holter monitoring is the diagnostic method of choice for both initial assessment and follow-up of patients with bradyarrhythmias. EPS remains an adjunctive diagnostic modality. Torsade de pointes not related to drugs. Patients with torsade de pointes associated with the long QT syndrome generally do not have inducible VT of any prognostic relevance and EPS is not useful in their management.130 Accessory bypass tracts and atrial fibrillation. In cardiac arrest survivors diagnosed as having WolffParkinson-White syndrome with rapid atria1 fibrillation,131 anatomic localization of the accessory pathway by activation mapping can be performed as a prelude to surgical or electrical ablation of the pathway.132 Coronary artery disease. Most data in electropharmacologic testing pertain to treatment of patients with coronary artery disease and prior myocardial infarction; it is in this patient population that EPS is of greatest benefit. In addition to optimal medical and/or surgical therapy,133,134 prevention of inducible

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sustained ventricular tachyarrhythmias provides a valid end point for therapy. Failure to suppress inducible VT by pharmacologic or surgical means is an accepted indication for the automatic implantable cardioverter-defibrillator. Management of patients with noninducibility at baseline is controversial; it is clear that no single approach will suffice. In such cases, patients may have VTIVF associated with unrecognized non-Q wave myocardial infarction or reversible ischemia without a stable electrophysiologic substrate for recurrent sustained VT. They may also have VT that is not due to reentry. The cause of cardiac arrest may be a bradyarrhythmia, or a nonarrhythmic event. In patients with VT/VF arrest, ambulatory monitoring is useful in the presence of frequent ectopy. Where arrhythmias are infrequent, empiric therapy with antiarrhythmic drugs can be used, but data indicate an increasing role for the implantable defibrillator.*35 SUMMARY

This review discusses the value and limitations of EPS in the management of cardiac arrest survivors. Uncertainties associated with EPS include a lack of consensus with respect to stimulation protocol, end points for VT suppression during drug testing, significance of induced polymorphic VT or VF, and timing of EPS after myocardial infarction. Despite methodologic shortcomings in most clinical studies, a useful body of knowledge has emerged. In cardiac arrest survivors, incidence of inducible sustained VT ranged from 35% to 75%. Where induced VT (sustained or nonsustained) was successfully suppressed, recurrent arrhythmic events occurred in 0 % to 33 % of patients over a l- to &year follow-up period. Failed regimens correlated with a high risk of arrhythmic recurrence. EPS also helps to select patients for the implantable defibrillator or electrocardiac surgery. In conclusion, EPS appears empirically useful in the management of cardiac arrest survivors with coronary artery disease; its value in other disease entities is uncertain.

REFERENCES

1. Liberthson RR, Nagel EL, Hirschman JC, Nussenfeld SR, Blackhourne BD, Davis JH. Pathophysiologic observations in prehospital ventricular fibrillation and sudden cardiac death. Circulation 1974;49:790. 2. Adgey AAJ, Scott ME, Allen JD, Nelson PG, Geddes JS, Zaidi SA, Pantridge JF. Management of ventricular fibrillation outside hospital. Lancet 1969;1:1169. 3. Baroldi G, Falzi G, Mariani F. Sudden coronary death. A postmortem study in 208 selected cases compared to 97 “control” subjects. AM HEART J 1979;98:20.

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4. Reichenbach DD, Moss NS, Meyer E. Pathology of the heart in sudden cardiac death. Am J Cardiol 1977;39:865. 5. Weaver WD, Larch GS, Alvarez HA, Cobb LA. Angiographic findings and prognostic indicators in patients resuscitated from sudden cardiac death. Circulation 1976;54:895. 6. Cobb LA, Baum RS, Alvarez H III, Schaffer WA. Resuscitation from out-of-hospital ventricular fibrillation: 4 years follow-uu. Circulation 1975:51:52 CSUDD~ IIIk223. 7. Liberthson RR, Nagel EL, ‘Hirschmad JC, Nussenfeld SR. Prehospital ventricular defibrillation. Prognosis and followup course. N Engl J Med 1974;291:317. 8. Schaffer WA, Cobb LA. Recurrent ventricular fibrillation and modes of death in survivors of out-of-hospital ventricular fibrillation. N Engl J Med 1975;293:259. 9. Myerburg RJ, Kessler KM, Estes D, Conde CA, Luceri RM, Zaman L, Kozlovskis PL, Castellanos A. Long-term survival after prehospital cardiac arrest: Analysis of outcome during an 8 year study. Circulation 1984;70:538. 10. Tresch DD, Keelan MH Jr, Siegel R, Troup PJ, Bonchek LI, Olinger GN, Brooks HL. Long-term survival after prehospital sudden cardiac death. AM HEART J 1984;108:1. 11. Graboys TB, Lown B, Podrid PJ, DeSilva R. Long-term survival of patients with malignant ventricular arrhythmia treated with antiarrhythmic drugs. Am J Cardiol 1982; 50:437. 12. Bigger JT, Fleiss JL, Kleiger R, Miller JP, Rolnitzky LM. The Multicenter Postinfarction Research Group. The relationship among ventricular arrhythmias, left ventricular dysfunction and mortality in the 2 years after myocardial infarction. Circulation 1984;69:250. 13. Wellens HJ, Schuilenberg RM, Durrer D. Electrical stimulation of the heart in patients with ventricular tachycardia. Circulation 1972;46:216. 14. Akhtar M, Damato AN, Batsford WP, Ruskin JN, Ogunkelu JB, Vargas G. Demonstration of re-entry within the HisPurkinje system in man. Circulation 1974;50:1150. 15. Denes P, Wu D, Dhingra RC, Amat-Y-Leon F, Wyndham C, Mautner RK, Rosen KM. Electrophysiological studies in patients with chronic recurrent ventricular tachycardia. Circulation 1976;54:229. 16. Anderson KP, Swerdlow CD, Mason JW. Entrainment of ventricular tachvcardia. Am J Cardiol 1984:53:335. 17. Brugada P, Weliens HJJ. Entrainment as an electrophysiologic phenomenon. J Am Co11 Cardiol 1984,3:451. 18. Joseohson ME. Horowitz LN. Snielman SR. Greenspan AM. VandePol C, Harken AH. Comparison of endocardial cathe: ter mapping with intraoperative mapping of ventricular tachycardia. Circulation 1980;61:395. 19. Horowitz LN, Josephson ME, Harken AH. Epicardial and endocardial activation during sustained ventricular tachycardia in man. Circulation 1987;61:1227. 20. Mason JW, Winkle RA. Accuracy of the ventricular tachycardia-induction study for predicting long-term efficacy and inefficacy of antiarrhythmic drugs. N Engl J Med 1980; 303:1073. 21. Mason JW, Winkle RA. Electrode-catheter arrhythmia induction in the selection and assessment of antiarrhythmic drug therapy for recurrent ventricular tachycardia. Circulation 197858971. 22. Horowitz LN, Josephson ME, Farshidi A, Spielman SR, Michelson EL, Greenspan AM. Recurrent sustained ventricular tachycardia. 3. Role of the electrophysiologic study in selection of antiarrhythmic regimens. Circulation 1978;58: 986. 23. Ruskin JN, Schoenfeld MH, Garan H. Role of electrophysiologic techniques in the selection of antiarrhythmic drug regimens for ventricular arrhythmias. Am J Cardiol 1983; 52:41C. 24. Horowitz LN, Spielman SR, Greenspan AM, Josephson ME. Role of programmed stimulation in assessing vulnerability to ventricular arrhythmias. AM HEART J 1982;103:604. 25. Hartzler GO, Maloney JD. Programmed ventricular stimu-

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lation in management of recurrent ventricular tachycardia. Mayo Clin Proc 1977;52:731. Fisher JF, Cohen HL, Mehra R, Altschuler H, Escher DJW, Furman S. Cardiac pacing and pacemakers. II. Serial electrophysiologic-pharmacologic testing for control of recurrent tachyarrhythmias. AM HEART J 1977;93:658. Denes P, Wu D, Wyndham C, Dhingra R, Baeurnfeind R, Swiryn S, Rosen KM. Chronic longterm electrophysiologic study of paroxysmal ventricular tachycardia. Chest 1980; 77~478. Horowitz LN, Josephson ME, Kastor JA. Intracardiac electrophysiologic studies as a method for the optimization of drug therapy in chronic ventricular arrhythmia. Prog Cardiovasc Dis 1980;23:81. Swerdlow CD, Gong G, Echt DS, Winkle RA, Griffin JC, Ross DL, Mason JW. Clinical factors predicting successful electrophysiologic-pharmacologic study in patients with ventricular tachycardia. J Am Co11 Cardiol 1983;1:409. Waxman HL, Sadowski LM, Horowitz LN, Harken AH, Josephson ME. Electrophysiologic study to guide medical and surgical therapy of sustained ventricular tachycardia: Long term predictive value (abstr). Circulation 1981;64(suppl IV):240. Swerdlow CD, Winkle RA, Mason JW. Determinants of survival in patients with ventricular tachyarrhythmias. N Engl J Med 1983;308:1436. Buxton AE, Josephson ME. Role of electrophysiologic studies in identifying arrhythmogenic properties of antiarrhythmic drugs. Circulation 1986;73(suppl-11):67. Au PK. Bhandari AK. Bream R. Schreck D. Siddiai R. Rahimtoola SH. Proarrhythmic effects of antiarrhythmic drugs during programmed ventricular stimulation in patients without ventricular tachycardia. J Am Co11Caridol 1987;9:389. Echt DS, Armstrong K, Schmidt P, Oyer PE, Stinson EB, Winkle RA. Clinical experience, complications and survival in 70 patients with the automatic implantable cardioverter/ defibrillator. Circulation 1985;71:289. Cox JL. The status of surgery for cardiac arrhythmias. Circulation 1985;71:413. Garan H, Nguyen K, McGovern B, Buckley M, Ruskin JN. Perioperative and long-term results after electrophysiologitally directed ventricular surgery for recurrent ventricular tachvcardia. J Am Co11 Cardiol 1986:8:201. Horowitz LN, Harken AH, Katsor JA, Josephson ME. Ventricular resection guided by epicardial and endocardial mapping for treatment of recurrent ventricular tachycardia. N Engl J Med 1980,302:589. Swerdlow C, Mason J, Stinson E, Oyer P, Winkle R, Derby G. Results of map-guided surgery in 103 patients with ventricular tachycardia (abstr). J Am Coll Cardiol 1985;5:409. Josephson ME, Harken AH, Horowitz LN. Long-term results of endocardial resection for sustained ventricular tachycardia in coronary disease patients. AM HEART J 1982;104:51. Mirowski M. The automatic implantable cardioverter-defibrillator: An overview. J Am Co11 Cardiol 1985;6:461. Livelli FD, Bigger JT, Reiffel JA, Gang ES,‘Patton JN, Noethline PM. Rolnitzkv LM. Glicklich JI. Remonse to programmed ventricular &imulation: Sensitivity, specificity and relation to heart disease. Am J Cardiol 1982;50:452. Nacarrelli GV, Prystowsky EN, Jackman WM, Heger JJ, l&hilly GT, Zipes DP. Role of electrophysiologic testing in managing patients who have ventricular tachycardia unrelated to coronarv arterv disease. Am J Cardiol 1982;50:165. ” ” Vandepol CJ, Farshidi A, Spielman SR, Greenspan AM, Horowitz LN, Joseuhson ME. Incidence and clinical sienificance of induced -ventricular tachycardia. Am J C&diol 1980;45:725. Brugada P, Abdollah H, Heddle B, Wellens HJJ. Results of

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a ventricular stimulation protocol using a maximum of 4 premature stimuli in patients without documented or susventricular arrhythmias. Am J Cardiol vetted i983;52:1214. Mann DE, Luck JC, Griffin JC, Herre JM, Limacher MC, Magro SA, Robertson NW, Wyndham CRC. Induction of clinical ventricular tachycardia using programmed stimulation: Value of third and fourth extrastimuli. Am J Cardiol 1983;52:501. Morady F, Shapiro W, Shen E, Sung RJ, Scheinman MM. Programmed ventricular stimulation in patients without spontaneous ventricular tachycardia. AM HEART J 1984; 107:875. Untereker WJ, Waxman HL, Waspe LE, Marchlinski FE, Buxton AE, Groh WC, Martin JL, Josephson ME. Programmed electrical stimulation in patients without clinical ventricular tachycardia (abstr). Circulation 1982;66(suppl 11):147. Waldo AL, Akhtar M, Brugada P, Henthorn RW, Scheinman MM, Ward DE, Wellens HJJ. The minimally appropriate electrophysiologic study for the initial assessment of patients with documented sustained monomorphic ventricular tachvcardia. J Am Co11 Cardiol 1985:6:1174. Robertson JF, Cain ME, Horowitz LN, Spiehnan SR, Greenspan AM, Waxman HL, Josephson ME. Anatomic and electrophysiologic correlates of ventricular tachycardia requiring left ventricular stimulation. Am J Cardiol 1981;48:263. Morady F, DiCarlo L, Winston S, Davis JC, Scheinman MM. A prospective comparison of triple extrastimuli and left ventricular stimulation in studies of ventricular tachvcardia induction. Circulation 1984;70:52. Lin HT. Mann DE. Luck JC. Maero SA. Sakun V. Wvndham CRC. Prospective comparisocof right-and leftve&icular stimulation in the induction of ventricular tachycardia (abstr). J Am Co11 Cardiol 1986;7:72A. Estes NAM III, Garan H, McGovern B, Ruskin JN. Influence of drive cycle length during programmed stimulation on induction of ventricular arrhythmias: Analysis of 403 patients. Am J Cardiol 1986;57:108. Herre JM, Mann DE, Luck JC, Magro SA, Figali S, Breen T, Wyndham CRC. Effect of increased current, multiple pacing sites and number of extrastimuli on induction of ventricular tachycardia. Am J Cardiol 1986;57:102. Kennedy EE, Rosenfeld LE, McPherson CA, Stark SI, Batsford WP. Mechanisms and relevance of arrhythmias induced by high-current programmed ventricular stimulation. Am J Cardiol 1986:57:598. Freedman RA, Swerdlow CD, Echt DS, Winkle RA, Soderholm-Difatte V, Mason JW. Facilitation of ventricular tachyarrhythmia induction by isoproterenol. Am J Cardiol 1984;54:765. Kerr CR, Ricci DR. Isoproterenol infusion challenge for the assessment of drug efficacy in patients with ventricular arrhythmias (abstr). Clin Res 1983;31:195A. Olshansky B, Martins JB. Usefulness of isoproterenol facilitation of ventricular tachycardia induction during extrastimulus testing in predicting effective chronic therapy with beta-adrenergic blockade. Am J Cardiol 1987;59:573. Brugada P, Green M, Abdollah H, Wellens HJJ. Significance of ventricular arrhythmias initiated by programmed ventricular stimulation: The importance of the type of ventricular arrhythmia induced and the number of premature stimuli required. Circulation 1984;69:87. Buxton AE, Waxman HL, Marchlinski FE, Untereker WJ Wasoe LE. Joseuhson ME. Role of trinle extrastimuli during electrophysiologic study of patients with documented sustained ventricular tachyarrhythmias. Circulation 1984;69:532. Reddy CP, Sartini JC. Nonclinical polymorphic ventricular tachycardia induced by programmed cardiac stimulation:

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Incidence, mechanisms and clinical significance. Circulation 1980;62:988. DiCarlo L, Morady F, Schwartz A, Shen E, Crevey B, Baermsn J, Krol R, Scheinman M, Sung R. Clinical significance of ventricular fibrillation-flutter induced by ventricular programmed stimulation in patients without prior ventricular tachycardia or fibrillation (abstr). J Am Co11Cardiol 1985;5:471. Morady F, DiCarlo LA, Baerman JM, de Buitleir M. Comparison of coupling intervals that induce clinical and nonclinical forms of ventricular tachycardia during programmed stimulation. Am J Cardiol 1986:57:1269. Mahmud R, Denker S, Lehmann MH, Tchou P, Dongas J, Akhtar M. Incidence and clinical significance of ventricular fibrillation induced with single and double ventricular extrastimuli. Am J Cardiol 1986;58:75. Henthorn RW, Moreira DAR, Olshansky B, Epstein AE, Waldo AL. Does induced “non-clinical” monomorphic ventricular tachycardia become manifest clinically? (abstr) J Am Co11 Cardiol 1987;9:109A. Woelfel A, Starek PJK, Foster JR, Noneman JW, Nichols TC, Gettes LS. Induction of ventricular tachycardia in patients with left ventricular aneurysms and no history of arrhvthmia (abstr). J Am Co11 Cardiol 1987:9:110A. Walier TJ, Spielman SR, Greenspan AM, Kutalek SP, Kay HR, Horowitz LN. Is prolongation of VT cycle length as good as noninducibility during EPS? (abstr) Circulation 1986:74(sunnl 11):214. Kudknchuck PJ, Kron J, Walance CG, Murphy ES, Morris CD. Griffith KK. McAnultv JH. Renroducibilitv of arrhvthmia induction with intracardiac electrophysiologic testing: Patients with clinical sustained ventricular tachyarrhythmias. J Am Co11 Cardiol 1986;7:819. Lombardi F. Stein J. Podrid PJ. Grabovs TB. Lown B. Dailv reproducibility of electrophysiblogic test results in malignant ventricular arrhythmia. Am J Cardiol 1986;57:96. 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 Cardiol 1985;55:689. de Buitleir M. Moradv F. DiCarlo LA. Baerman JM. Krol RB. Immediate reproducibility of clinical and nonclinical forms of induced ventricular tachycardia. Am J Cardiol 1986;58:279. Ruskin JN, DiMarco JP, Garan H. Out-of-hospital cardiac arrest. Electrophysiologic observations and selection of long-term antiarrhythmic therapy. N Engl J Med 1980;303:607. Platia EV, Reid PR. Nonsustained ventricular tachycardia during programmed ventricular stimulation: Criteria for a positive test. Am J Cardiol 1985;56:79. Roy D, Waxman HL, Kienzle MG, Buxton AE, Marchlinski FE, Josephson ME. Clinical characteristics and long-term follow-up in 119 survivors of cardiac arrest: Relation to inducibilitv at electronhvsioloaic testing. Am J Cardiol 1983;52:96& Swerdlow CD, Winkle RA, Mason JW. Prognostic significance of the number of induced ventricular complexes during assessment of therapy for ventricular tachyarrhythmias. Circulation 1983;68:400. Hamer AW, Finerman WB Jr, Peter T, Mandel WJ. Disparity between the clinical and electrophysiologic effects of a&odarone in the treatment of recurrent ventricular tachvarrhvthmias. AM HEART J 1981;102:992. Morady F, Scheinman MM, Hess DS. Amiodarone in the management of patients with ventricular tachycardia and ventricular fibrillation. PACE 1983:6:609. Nademanee K, Hendrickson J, Kannan R, Singh BN. Antiarrhythmic efficacy and electrophysiologic actions of amiodarone in patients with life-threatening ventricular arrhythmias: Potent suppression of spontaneously occurring tachyarrhythmias versus inconsistent abolition of induced ventricular tachycardia. AM HEART J 1982;103:950. -I

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76. Heger JJ, Prystowsky EN, Jackman WM, Naccarelli GV, Warfel KA, Rinkenberger RL, Zipes DP. Amiodsrone. Clinical efficacy and electrophysiology during long-term therapy for recurrent ventricular tachycardia or ventricular fibrillation. N Engl J Med 1981;305:539. 77. Kim SG, Felder SD, Figura I, Johnston DR, Waspe LE, Fisher JD. Comparison of programmed stimulation and Holter monitoring for predicting long-term efficacy and inefficacy of amiodarone used alone or in combination with a class 1A antiarrhythmic agent in patients with ventricular tachyarrhythmia. J Am Co11 Cardiol 1987;9:398. 78. Heger JJ, Hubbard J, Zipes DG, Miles WM, Prystowsky EN. Propafenone treatment of recurrent ventricular tachycardia: Comparison of continuous electrocardiographic recording and electrophysiologic study in predicting drug efficacy. Am J Cardiol 1984;54:40D. 79. Horowitz LN, Greenspan AM, Spielman SR, Webb CR, Morganroth J, Rotmensch H, Sokoloff NM, Rae AP, Segal BL, Kay HR. Usefulness of electrophysiologic testing in evaluation of amiodarone therapy for sustained ventricular tachyarrhythmias associated with coronary heart disease. Am J Cardiol 1985;55:367. 80. McGovern B, Garan H, Malacoff RF, DiMarco JP, Grant G, Sellers DT. Ruskin J. Lone-term clinical outcome of ventricular tachycardia or fibrillation treated with amiodarone. Am J Cardiol 1984;53:1558. 81. Gomoll AW, Byrne JE, Antonaccio MJ. Electrophysiology, hemodynamic and arrhythmia efficacy model studies on encainide. Am J Cardiol 1986;58:1OC. 82. Yabek SM, Kato R, Singh BN. Effects of amiodarone and its metabolite, desethylamiodarone, on the electrophysiologic properties of isolated cardiac muscle. J Cardiovasc Pharmaco1 1986;8:197. 83. Roden DM, Reele SB, Higgins SB, Wilkinson GR, Smith RF, Oates JA, Woosley RL. Antiarrhythmic efficacy, pharmacokinetics and safety of N-acteylprocainamide in human subjects: Comparisons with procainamide. Am J Cardiol 1980;46:463. 84. Latini R, Connolly SJ, Kates RE. Myocardial dispostion of amiodarone in the dog. J Pharmacol Exp Therap 1983; 224:603. 85. Connolly SJ, Latini R, Kates RE. Pharmacodynamics of intravenous amiodarone in the dog. J Cardiovasc Pharmacol 1984;6:531. 86. Spielman SR, Schwartz JS, McCarthy DM, Horowitz LN, Greenspan AL, Sadowski LM, Josephson ME, Waxman HL. Predictors of the success or failure of medical therapy in patients with chronic recurrent sustained ventricular tachycardia: A discriminant analysis. J Am Co11 Cardiol 1983; 1:401. 87. Buxton AE, Waxman HL, Marchlinski FE, Josephson ME. Electrophysiologic studies in nonsustained ventricular tachycardia. Relation to underlying heart disease. Am J Cardiol 1983;52:985. 88. Das SK, Morady F, DiCarlo L, Baerman J, Krol R, De Buitleir M, Crevey B. Prognostic usefulness of programmed ventricular stimulation in idiopathic dilated cardiomyopathy without symptomatic ventricular arrhythmias. Am J Cardiol 1986;58:998. 89. Kuck KH, Costard A, Geizer M, Kunze KP. Programmed electrical stimulation in hypertrophic cardiomyopathy; stimulation results in patients with and without cardiac arrest or syncope (abstr). J Am Co11 Cardiol 1987;9:964. 90. Borggrefe M, Podczeck A, Breitherdt G. Electrophysiologic studies in hypertrophic cardiomyopathy (abstr). Circulation 1986;74(suppl 11):482. 91. Morady F, Shen E, Bhandari A, Schwartz A, Scheinman MM. Programmed ventricular stimulation in mitral valve prolapse: Analysis of 36 patients. Am J Cardiol 1984;53:135. 92. Poll DS, Marchlinski FE, Buxton AE, Josephson ME. Usefulness of programmed stimulation in idiopathic dilated cardiomyopathy. Am J Cardiol 1986;58:992.

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93. Bhandari AK, Au PK, Rose JS, Kotlewski A, Blue S, Rahimtoola SH. Decline in inducibility of sustained ventricular tachycardia from two to twenty weeks after acute myocardial infarction. Am J Cardiol 1987;59:284. 94. McComb JM, Gold HK, Leinbach RC, Ruskin JN, Garan H. Reproducibility of the results of -programmed ventricular stimulation early and late after acute myocardial infarction (abstr). J Am Coll Cardiol 198637:129A. 95. Brugada P, Waldecker B, Kersschot Y, Zehender M, Wellens HJJ. Ventricular arrhythmias initiated by programmed stimulation in four groups of patients with healed myocardial infarction. J Am Co11 Cardiol 1986;8:1035. 96. Kuck KH, Costard A, Schluter M, Kunze KP. Significance of timing programmed electrical stimulation after acute myocardial infarction. J Am Coll Cardiol 1986;8:1279. 97. Marchlinski FE, Buxton AE, Waxman HL, Josephson ME. Identifying patients at risk of sudden death after myocardial infarction: Value of the response to programmed stimulation, degree of ventricular ectopic activity and severity of left ventricular dysfunction. Am J Cardiol 1983;52:1190. 98. Roy D, Marchand E, Theroux P, Waters DD, Pelletier GB, Bourassa MG. Programmed ventricular stimulation in survivors of an acute myocardial infarction. Circulation 1985; 12~487. 99. Richards DA, Cody DV, Denniss AR, Russell PA, Young AA, Uther JB. Ventricular electrical instability: A predictor of death after myocardial infarction. Am J Cardiol 1983;51:75. 106. Hamer A, Vohra J, Hunt D, Sloman G. Prediction of sudden death by electrophysiologic studies in high risk patients surviving acute myocardial infarction. Am J Cardiol 1982; 50:223. 101. Stevenson WG, Brugada P, Kersschot I, Waldecker B, Zehender M, Geibel A, Wellens HJJ. Electropbysiologic characteristics of ventricular tachycardia or fibrillation in relation to age of myocardial infarction. Am J Cardiol 1986;57:387. 102. Malliani A, Schwartz PJ, Zanchetti A. Neural mechanisms in life-threatening arrhythmias. AM HEART J 1980;100:705. 103. Fuster V, Steele P, Chesebro JH. Role of platelets and thrombosis in coronary atherosclerotic disease and sudden death. J Am Co11 Cardiol 1985;5:175B. 104. Davies MJ, Thomas AC, Knapman PA, Hangartner JR. Intramyocardial platelet aggregation in patients with unstable angina suffering sudden ischemic cardiac death. Circulation 1986;73:418. 105. Langberg JJ, Ports T, Sauve MJ, Scheinman MM. Coronary spasm and aborted sudden death in patients without structural heart disease (abstr). Circulation 1986;74(suppl 1I):ll. 106. Dubois C, Pierard LA, Smeets JP, Foidart G, Demoulin JC, Tulippe C, Kulbertus HE. Ventricular fibrillation in the early phase of myocardial infarction (abstr). Circulation 1986;74(suppl 1I):lO. 107. Nicod P, Gilpin E, Dittrich H, Ross J. Clinical outcome of patients who have early ventricular fibrillation after mvocardial infarction (abstr). J Am Coll Cardiol 1987;9:24OA. 108. Cobb LA, Werner JA, Trobaueh G. Sudden cardiac death. II. Outcome of resuscitation, management and future directions. Mod Concepts Cardiovasc Dis 1980;49:37. 109. Panidis IP, Morganroth J. Initiating events of sudden cardiac death. In: Josephson ME, editor. Sudden cardiac death. Cardiovascular Clinics. Philadelphia: FA Davis Co, 198581. 110. Nikolic G, Bishop RL, Singh JB. Sudden death recorded during Holter monitoring. Circulation 1982;66:218. 111. Pratt CM, Francis MJ. Luck JC. Wvndbam CR. Miller RR. Quinones .MA. Analysis of ambulatory electrocardiograms in 15 patients during spontaneous ventricular fibrillation with special reference to preceding arrhythmic events. J Am Coll Cardiol 1983;2:789. 12. Stevenson WG, Brugada P, Waldecker B, Zehender M, Wellens HJJ. Clinical, angiographic, and electrophysiologic

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findings in patients with aborted sudden death as compared with patients with sustained ventricular tachycardia after myocardial infarction. Circulation 1985;71:1146. 112a. Freedman RA, Swerdlow CD, Soderholm-Difatte V, Mason JW. Prognostic significance of arrhythmias induced at electrophysiologic study in cardiac arrest survivors (abstr). Circulation 1985;72(suppl 111):45. 113. Benditt DG, Benson DW, Klein GJ, Pritzker MR, Kriett JM, Anderson RW. Prevention of recurrent sudden cardiac arrest: Role of provocative electropharmacologic testing. J Am Co11 Cardiol 1983;2:418. 114. Kehoe RF, Moran JM, Zheutlin T, Tommaso C, Lesch M. Electrophysiological study to direct therapy in survivors of pre-hospital ventricular fibrillation (abstr). Am J Cardiol 1982;49:928. 115. Kehoe RF, Zheutlin T, Mattioni T, Parker M, Teagarden R. Factors associated with time to arrhythmic recurrence in survivors of ventricular fibrillation (abstr). J Am Co11 Cardiol1987;9:108A. 116. Zheutlin T, Steinman R, Summers C, Weinberg S, Kehoe R. Long-term outcome in survivors of cardiac arrest with non-inducible ventricular tachycardia during programmed stimulation (abstr). Circulation 1984,7O(suppl 11):399. 117. Morady F, Scheinman MM, Hess DS, Sung RJ, Shen E, Shapiro W. Electrophysiologic testing in the management of survivors of out-of-host&al cardiac arrest. Am J Cardiol 1983;51:85. 118. Skale BT, Miles WM, Heger JJ, Zipes DP, Prystowsky EN. Survivors of cardiac arrest: Prevention of recurrence by drug therapy as predicted by electrophysiologic testing or electrocardiographic monitoring. Am J Cardiol 1986;57:113. 119. Ruskin JN, Garan H, DiMarco JP, Kelly E. Electrophysiologic testing in survivors of prehospital cardiac arrest: Therapy and long-term follow-up (abstr). Am J Cardiol 1982;49:958. 120. Wilber DJ, Garan H, Kelly E, McGovern B, Newell J, Ruskin JN. Out-of-hospital cardiac arrest: Role of electrophysiologic testing in prediction of long-term outcome (abstr). Circulation 1986;74:482. 121. Morady F, DiCarlo L, Winston S, Davis JC, Scheinman MM. Clinical features and prognosis of patients with out of hospital cardiac arrest and a normal electrophysiologic study. J Am Co11 Cardiol 19&1;4:39. 122. Platia EV, Reid PR. Predictive clinical value of sustained and nonsustained ventricular tachycardia induction in survivors of sudden cardiac death (abstr). J Am Co11 Cardiol 1983;1:585. 122a. Eldar M, Sauve MJ, Abbott JA, Ruder MA, Scheinman MM. Aborted sudden death: Lone-term follow-up (abstr). Circulation 1985;72 (suppl 111):44.123. Swerdlow CD, Bardy GH, McAnulty JH, Kron J, Lee JT, Greene LH. Northwest Electronhvsiology Society. Timing of electrophysiologic testing after out-of-hospital ventricular fibrillation: Is there a statute of limitations? (abstr) Circulation 1985;72(suppl 111):45. 124. Gradman AH, Batsford WP, Rieur EC, Leon L, Van Zetta AM. Ambulatory electrocardiographic correlates of ventricular inducibility during programmed electrical stimulation. J Am Co11 Cardiol 1985;5:1087. 125. Anderson JL, Mason JW. Testing the efficacy of antiarrhythmic drugs. N Engl J Med 1986,315:391. 126. Kim SG, Seiden SW, Felder SD, Waspe LE, Fisher JD. Is programmed stimulation of value in predicting the longterm success of antiarrhythmic therapy for ventricular tachycardias? N Engl J Med 1986;315:356. ._- - _. 126a. Kuchar DL, Thorburn CW, Sammel NL. Prediction of serious arrhythmic events after myocardial infarction: Signal-averaged electrocardiogram, Holter monitoring and radionuclide ventriculography. J Am Co11 Cardiol 1987;9:531. 126b. Nalos PC, Gang ES, Mandel WJ, Ladenheim ML, Lass Y, Peter T. The signal-averaged electrocardiogram as a screen.

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ing test for inducibility of sustained ventricular tacbycardia in high risk patients: A prospective study. J Am Co11Cardiol 1987;9:539. Liem BL, Ovadia M, Sasson Z, Franz MR, Swerdlow CD. Value of electrophysiologic study in patients with idiopathic dilated cardiomyopathy and sustained ventricular tachyarrhythmias (abstr). J Am Co11 Cardiol 1987;9:107a. Kowey PR, Eisenberg R, Engel TR. Sustained arrhythmias in hypertrophic obstructive cardiomyopathy. N Engl J Med 1984;310:1566. Tracy CM, Winkler J, Leon MB, Tucker EE, Cannon RO, Del Negro A, Epstein SE. Role of electrophysiologic studies in patients with hypertrophic cardiomyopathy (abstr). J Am Co11 Cardiol 1987;923OA. Bhandari AK, Shapiro WA, Morady F, Shen EN, Mason J, Scheinman MM. Electrophysiologic testing in patients with the long QT syndrome. Circulation 1985;71:63. Klein GJ, Bashore TM, Sellers TD, Pritchett ELC, Smith WM, Gallagher JJ. Ventricular fibrillation in the WolffParkinson-White syndrome. N Engl J Med 1979;301:1080.

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132. Fischell TA, Stinson EB, Derby GC, Swerdlow CD. Longterm follow-up after surgical correction of Wolff-ParkinsonWhite syndrome. J Am Co11 Cardiol 1987;9:283. 133. Tresch DD. Wetherbee JN. Siegel R. Troun PJ. Keelan MH. Olinger GN, Brooks HL. Long’-term follow-up of survivors of prehospital sudden cardiac death treated with coronary bypass surgery. AM HEART J 1985;110:1139. 134. Holmes DR, Davis KB, Mock MB, Fisher LD, Gersh BJ, Killip T III, Pettinger M. Participants in the Coronary Artery Surgery Study. The effect of medical and surgical treatment on subsequent sudden cardiac death in patients with coronary artery disease: A report from the Coronary Artery Surgery Study. Circulation 1986;73:1254. 135. Veltri EP, Mower MM, Mirowski M, Fisher S, Juanteguy J, Watkins L, Reid PR, Griffith LSC. Clinical outcome of patients with noninducible ventricular arrhythmias and the automatic implantable defibrillator. Circulation 1986;74 (suppl 11):109.

with v

George F. Van Hare, M.D., Lynn J. Soffer, M.D., Mark C. Sivakoff, Jerome Liebman, M.D. Cleveland, Ohio

Isolated ventricular septal defect (VSD) is the most common serious congenital heart defect encountered in pediatric cardiology, accounting for 30% of all patients seen by pediatric cardiologists’ and occurring with an incidence of 1.5 to 2.5 per 1000 live births.‘p2 There has long been debate concerning the indications for, and timing of, definitive cardiac surgery for this lesion, as well as debate concerning the risk of pulmonary vascular disease in children with large VSDs. The surgical management of patients with large VSDs has evolved over the past 25 years, from early pulmonary artery banding in the 1950s and 1960s to the current practice of

From the Division of Pediatric Cardiology, Department of Pediatrics, Rainbow Babies and Childrens Hospital, and the Department of Biometry, Case Western ReserveUniversity School of Medicine. Supported in part by National Library of Medicine grant Z-TXIMo9ool. Received for publication Feb. 3, 1987; accepted May 12, 1987. Reprint requests: Jerome Liebman, M.D., Rainbow Babies and Childrens Hospital, Cleveland, OH 44106.

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Hosrt Journal

M.D., and

complete repair for many patients at an early age. We report here our experience with patients who underwent cardiac catheterization, particularly those who underwent serial catheterization, with respect to the outcome of medical management and surgical repair and the risk for development of pulmonary vascular disease. METHODOLOGY

The sources of patient information consisted of original cardiac catheterization reports, inpatient and outpatient charts, and ECGs. To identify patients, diagnoses were examined from all cardiac catheterizations performed at our institution from June 1960 through 1984. Patients with the diagnosis of simple ventricular septal defect with left-to-right shunt were included in the study. Excluded from the study were patients with other serious congenital cardiac defects. Also excluded were patients with pulmonary stenosis on the initial catheterization. The patients were categorized by the size of the defect, as assessed by the ratio of right-to-left