Prediction of Sustained Ventricular Tachycardia Inducible by Programmed Stimulation in Patients With Coronary Artery Disease
Utility of Clinical Variables
Background—Cardiologists often use clinical variables to determine the need for electrophysiological studies to stratify patients for risk of sudden death. It is not clear whether this is rational in patients with coronary artery disease, left ventricular dysfunction, and nonsustained ventricular tachycardia.
Methods and Results—We analyzed the first 1721 patients enrolled in the Multicenter UnSustained Tachycardia Trial to determine whether clinical variables could predict which patients would have inducible sustained monomorphic ventricular tachycardia. The rate of inducibility of sustained ventricular tachycardia was significantly higher in patients with a history of myocardial infarction and in men compared with women. There was a progressively increased rate of inducibility with increasing numbers of diseased coronary arteries. There was a significantly lower rate of inducibility in patients with prior coronary artery bypass surgery and in patients who also had noncoronary cardiac disease. The rate of inducibility was higher in patients of white race, patients with recent (≤6 weeks) angina, left ventricular dyskinesis, and in patients with greater numbers of fixed thallium defects. Inducibility was more likely in patients who had a prior myocardial infarction complicated by congestive heart failure, ventricular tachycardia, or fibrillation ≤48 hours after the onset of infarction. Although these associations are statistically significant, the accuracy of the clinical variables in discriminating between patients with and those without inducible ventricular tachycardia is only modest (receiver operator characteristic area <0.70).
Conclusions—Multiple clinical variables are independently associated with inducible sustained ventricular tachycardia. However, they have limited utility to guide clinical decisions regarding the use of electrophysiological testing for risk stratification in this patient population.
Although new treatments for acute myocardial infarction have reduced the mortality rates of patients with acute infarction, late complications persist. Survivors of the acute phase of infarction with significant left ventricular dysfunction are at particular risk, with a 6-month mortality rate of ≥10%.1 Sudden death continues to account for at least one third of the deaths, and half the sudden deaths occur ≥1 year after infarction.2 3 A number of techniques, such as ambulatory ECG monitoring and evaluation of left ventricular function, can risk-stratify patients with prior myocardial infarction. However, these factors do not identify patients specifically at risk for sudden death. Thus identification of patients at high risk for sudden death poses a major problem for clinicians.
One technique that is specific for prediction of sudden death is programmed electrical stimulation.4 5 Clinicians in practice often make decisions regarding which patients should undergo electrophysiological testing on the basis of the characteristics of nonsustained ventricular tachycardia and clinical factors such as ejection fraction and extent of coronary artery disease. We have demonstrated previously that ECG characteristics of spontaneous nonsustained ventricular tachycardia have no relation to inducibility of sustained ventricular tachycardia.6 7 The purpose of the present analysis was to identify clinical factors that might predict patients with coronary artery disease having sustained ventricular tachycardia inducible by programmed stimulation.
We examined characteristics of the first 1721 patients enrolled in the Multicenter UnSustained Tachycardia Trial (MUSTT). The primary aim of this study is to determine whether antiarrhythmic therapy guided by electrophysiological testing will reduce the risk of sudden death in patients with chronic coronary artery disease.
All patients met the entry criteria, which included the presence of documented coronary artery disease, left ventricular ejection fraction ≤0.40, and asymptomatic nonsustained ventricular tachycardia documented ≥96 hours after myocardial infarction, coronary angioplasty, or coronary artery bypass surgery. Coronary artery disease was established by coronary angiography or documentation of an acute myocardial infarction. We attempted vigorously (by review of hospital charts and angiographic reports) to verify that left ventricular dysfunction was attributable to coronary disease to exclude patients with nonischemic cardiomyopathies and incidental coronary artery disease. Details of the study protocol have been published previously.8 The median duration and cycle length of spontaneous nonsustained ventricular tachycardia were 5 complexes and 420 ms, respectively.6
The protocol for electrophysiological studies, standardized at all participating centers, included delivery of 1, 2, and 3 ventricular extrastimuli at 2 right ventricular sites at pacing cycle lengths of 600 and 400 ms and bursts of 5 to 15 ventricular stimuli at cycle lengths of 350 to 250 ms. The end point was the induction of sustained (duration ≥30 seconds) ventricular tachycardia or fibrillation or completion of the protocol. Although reproducible induction was the goal, investigators had the option to refrain from continuing stimulation if the initial induction resulted in a tachycardia that caused loss of consciousness. Patients with sustained monomorphic ventricular tachycardia induced at any point in the stimulation protocol and those with sustained polymorphic ventricular tachycardia or ventricular fibrillation induced by 1 or 2 extrastimuli were eligible for randomization. All consenting patients, regardless of whether randomizable ventricular tachycardia was induced, were included in the study.
Each participating center’s institutional review board approved the study protocol. All subjects gave written informed consent.
We analyzed characteristics listed in Table 1⇓ for their relation to inducible sustained monomorphic ventricular tachycardia. Most factors were obtained by review of the patient’s history. Location(s) of myocardial infarction(s) were determined by ECG and patient history. Extent of coronary disease was examined among patients who had undergone coronary angiography and was expressed as the number of vessels with ≥75% reduction in luminal diameter. Left ventricular ejection fraction was determined by echocardiography, radionuclide angiography, or contrast ventriculography. Patients were required to complete a symptom-limited exercise test, with perfusion imaging if clinically appropriate, within 6 months before enrollment. If catheterization was performed within 12 months of enrollment and the stress test results would not alter the patient’s treatment, it could be omitted at the investigator’s discretion.
Data were reported on standardized case report forms. Accuracy of data was verified by 1 of 2 highly trained nurses experienced in performance of cardiac catheterization and electrophysiological studies. All data items were checked against source documents. A core laboratory reviewed ECG tracings of sinus rhythm and all episodes of induced ventricular tachycardia.
Clinical characteristics were summarized in terms of frequencies and percentages for categorical variables and by the median, 25th, and 75th percentiles for continuous variables. We used logistic regression analysis to examine individual and joint relations between clinical characteristics and inducible sustained monomorphic ventricular tachycardia. We used a flexible model-fitting approach with cubic splines (polynomials) to characterize possible nonlinear relations between continuous predictor variables and inducibility.9 10
Among clinical characteristics considered potential predictors of inducibility, availability of data varied. Although clinical features (eg, demographics, cardiac history) were complete in almost every patient, for some variables there were subsets of patients with missing data. For instance, information on the anatomic extent of coronary disease was not available in all patients because angiography was not mandated as an enrollment criterion. Exercise test data were not available in all patients. For univariate analyses, all available information for each clinical characteristic was used. For multivariable analyses, several models were assessed in a hierarchical fashion, seeking first to identify independent predictors of inducibility from a set of variables where the data were relatively complete (model 1 in Table 4⇓) and then adding other variables where fewer data were available.
The area under the receiver operating characteristic (ROC) curve was used to quantify the ability of the clinical characteristics to predict inducibility accurately. An area under the ROC curve near 0.5 indicates that predictions of inducibility are essentially random with respect to actual inducibility. An ROC area near 1.0 indicates that the predictions correctly discriminate between patients who do and those who do not have inducible sustained monomorphic ventricular tachycardia.
We examined the relation of patient characteristics with inducibility of both sustained monomorphic ventricular tachycardia and all randomizable ventricular tachycardia (as defined above). We also examined these relations for patients with inducible sustained monomorphic tachycardia with cycle length >230 ms.
Data from 1721 patients were analyzed. Sustained monomorphic ventricular tachycardia was inducible in 549 (32%) patients, with a median cycle length of 243 ms (25th, 75th percentiles: 225 and 270 ms). Characteristics of the 549 patients with inducible sustained monomorphic ventricular tachycardia and the total population appear in Table 1⇑. Most patients had a history of myocardial infarction. The remaining patients had data consistent with an ischemic cardiomyopathy, for example, triple-vessel coronary disease and diffuse left ventricular dysfunction. The patients are similar to other reported patient populations with prior myocardial infarction with respect to age, sex, extent of coronary artery disease, and use of thrombolytic therapy.
Several variables were significantly associated with inducibility by univariate analysis (Table 2⇓). The time from most recent myocardial infarction was significantly longer in patients with inducible ventricular tachycardia. No outcome of exercise tests including symptoms, ECG evidence of ischemia, or reversible thallium defects were associated with inducible ventricular tachycardia (Figure 1⇓). However, markers of extensive myocardial infarction, such as increasing numbers of fixed thallium defects (Figure 1⇓) and the presence of dyskinesis, were associated with inducible ventricular tachycardia. The left ventricular ejection fraction did not distinguish patients with inducible sustained ventricular tachycardia. After accounting for the predictive information in history of myocardial infarction, a history of congestive heart failure ≥48 hours and ventricular tachyarrhythmias occurring ≤48 hours after the onset of infarction were also associated with inducible tachycardia (Figure 2⇓). Infarct location was not independently associated with inducible tachycardia.
The relation between inducibility, extent of coronary disease, and prior bypass grafting (CABG) was complex. When all 1450 patients with data on coronary artery anatomy and history of CABG were examined, a nonsignificant trend toward a higher frequency of inducible ventricular tachycardia with increasing disease severity was observed (Table 3⇓). We then examined the relation between coronary anatomy and inducibility, controlling for prior CABG. There are clear trends to increased frequencies of inducible tachycardia with increasing severity of coronary disease, both in patients with and those without prior CABG. Furthermore, the reduced frequency of inducible tachycardia in patients with prior CABG is more evident for each degree of coronary artery disease.
To evaluate these relations further, we examined them only in patients with a history of prior myocardial infarction. Analyzed in this manner, a history of prior thrombolytic therapy and performance of an exercise test were no longer significantly associated with inducible ventricular tachycardia. The other variables in Table 2⇑ retained their statistically significant relations with inducible ventricular tachycardia.
Although the univariate analyses revealed factors associated significantly with inducible tachycardia, differences in the rate of inducibility across the levels of any individual factor were not sufficiently pronounced to predict accurately which patients would have inducible tachycardia. To determine which of the characteristics analyzed represent independent predictors of inducible sustained monomorphic ventricular tachycardia, we constructed several multivariable logistic regression models (Table 4⇓). The higher likelihood of inducibility in patients with a history of recent angina and more severe coronary disease and the lower likelihood of inducibility in women and in patients with prior CABG were all independently significant. In addition to the models shown in Table 4⇓, an analysis was performed in which the number of fixed defects on thallium imaging was considered jointly with the variables in model 3. Although inclusion of the thallium data reduced the number of patients to less than one third of the overall population, in patients in whom this information was available, the number of fixed defects was a significant predictor of inducibility (χ2=4.0, P=0.045). However, with ROC areas ranging from only 0.60 to 0.70 for all the models, no combination of clinical variables was found that could discriminate between patients with or those without inducible monomorphic ventricular tachycardia with a high degree of accuracy.
We repeated the analyses noted above, including all patients with randomizable ventricular tachycardias (ie, both the 549 patients with monomorphic and 63 with polymorphic sustained ventricular tachycardias) as the end point. The results of this analysis did not differ from that with inducible monomorphic ventricular tachycardia used as the end point. We performed an analysis considering the 149 patients with inducible sustained monomorphic tachycardia having a cycle length ≤230 ms as noninducible. The only change was that β-adrenergic–blocking agent use was no longer associated with inducibility.
Our major finding is that clinical variables have limited utility to guide clinical decisions regarding the use of electrophysiological testing for risk stratification in the study population. The analysis does demonstrate a number of clinical characteristics that are statistically associated with inducible sustained ventricular tachycardia. However, the relations noted are not distinct enough to predict accurately patients with and patients without inducible ventricular tachycardia.
Several of the factors that differ between patients with and patients without inducible sustained monomorphic ventricular tachycardia were not anticipated, such as the associations of race and recent angina. Likewise, it is not clear why patients receiving β-blocking agents at the time of enrollment had a higher inducibility rate. This should not be interpreted as contradicting the proven effects of β-adrenergic–blocking agents to reduce mortality rates in survivors of myocardial infarction. It seems likely that some of these associations are due to selection bias. The relations of exercise testing and thrombolytic therapy with inducible tachycardia are likely due to the association between these variables and occurrence of a prior myocardial infarction.
Certain estrogens have been demonstrated to inhibit cardiac fibroblast growth.11 Since the presence of inducible ventricular tachycardia is thought to be dependent in part on scar formation after healing of myocardial infarction, this effect may explain the significantly lower rates of inducible tachycardia in women.
The negative association between a history of CABG and inducible tachycardia suggests that correcting ischemia may reduce the development of reentrant circuits leading to inducible tachycardias. It is clear (Table 3⇑) that there was an uneven distribution of coronary artery bypass grafting, dependent on the extent of coronary artery disease. Patients with more extensive coronary disease were more likely to have undergone prior CABG. The relatively fewer patients with single-vessel disease who had undergone prior CABG had a low prevalence of inducible ventricular tachycardia. Conversely, the small number of patients with triple-vessel disease who had not undergone prior CABG had a relatively high prevalence of inducible ventricular tachycardia. When coronary anatomy was considered alone as a predictor of inducibility, the inducibility rate in single-vessel disease was weighted heavily by patients without prior CABG, whereas the inducibility rate in 3-vessel disease was weighted heavily by patients with a prior CABG. This resulted in a lesser gradient of inducible tachycardia versus extent of coronary disease when patients with and patients without CABG were grouped together. Thus the effects of prior CABG confound the relation of coronary anatomy to inducibility. The lower rate of inducible tachycardia in patients with prior CABG may explain in part the failure of implantable cardioverter/defibrillators to reduce mortality rates in the CABG-Patch Trial.12
The observation that a greater time had elapsed after infarction for patients with inducible tachycardia than for those without inducible tachycardia may be a function of selection bias. Patients with inducible tachycardia that was more likely to occur spontaneously (for unknown reasons) may have previously developed spontaneous sustained tachycardia, thus eliminating themselves from participation in this trial. Alternatively, it is possible that the relation between time from infarction and inducibility is due to chronic “remodeling” of scar, late after infarction.
Prior studies have suggested that increased size of myocardial infarction correlates with an increased likelihood of inducible ventricular tachycardia. This may explain the association between inducible tachycardia and a history of myocardial infarction, number of fixed thallium defects, presence of dyskinesis, and history of congestive heart failure or ventricular tachyarrhythmias complicating a prior acute infarction. Failure of left ventricular ejection fraction to predict inducible tachycardia probably relates to the entry requirement of an ejection fraction ≤0.40. The negative association between “other” (noncoronary) cardiac disease may be explained by a significant contribution of the noncoronary disease to these patients’ left ventricular dysfunction. Such patients may have sustained smaller myocardial infarctions. The lack of association between indexes of myocardial ischemia revealed by stress testing is not surprising, as there is no evidence that active ischemia causes monomorphic ventricular tachycardia inducible by programmed stimulation.
Previous analyses of electrophysiological studies in patients with nonsustained ventricular tachycardia complicating coronary artery disease have been limited by small sample size.13 14 15 16 17 18 Studies that included patients regardless of the measured left ventricular ejection fraction have noted associations between a lower ejection fraction and inducible ventricular tachycardia.13 14 15 16 An analysis restricted to patients with ejection fraction <0.40 did not confirm these observations.18 It seems likely that if one selects patients on the basis of significant left ventricular dysfunction, further stratification for the likelihood of finding inducible sustained ventricular tachycardia is not possible. Klein and Machell15 also noted a link between akinesis or dyskinesis and inducible ventricular tachycardia.
Several studies examined the results of electrophysiological testing after recent myocardial infarction, without requiring the presence of nonsustained ventricular tachycardia or reduced ejection fraction. These analyses have found a number of factors to be associated with inducible ventricular tachycardia. In contrast to our findings, reperfusion with streptokinase during acute infarction has correlated with a decreased likelihood of inducing ventricular tachycardia in small studies.19 20 The reason for these differences is not clear. McComb et al21 also noted an association between male sex and inducible ventricular tachycardia in patients who received thrombolytic therapy for acute infarction. Others have not found this association.22 23 24 25 26 McComb et al also noted an association between inducible tachycardia and extent of coronary artery disease, but other investigators have not.22 24 27 Some report that patients with recent anterior infarction are less likely to have inducible ventricular tachycardia,21 27 28 but others have not.23 24 Most investigators studying unselected patients after recent infarction have noted a significant association between inducible ventricular tachycardia and decreased ejection fraction,25 27 28 29 although some have not.22 23 24 Finally, left ventricular aneurysms have been associated with inducible ventricular tachycardia by some workers24 25 but not by others.23 27 The present study is based on a data set larger than all these previously published studies combined and should help to clarify the clinical relevance of these factors.
This study’s major limitations are also its points of major interest. Although several factors were associated significantly with inducible ventricular tachycardia, these relations have only modest clinical utility at this time. For example, although women were significantly less likely than men to have inducible ventricular tachycardia, the values are not such that we would recommend against performing electrophysiological studies in women having the characteristics of patients in this study. Furthermore, our observations should not be extrapolated to all patients with coronary disease or prior myocardial infarction. Rather, they are applicable only to patients with demonstrated coronary artery disease, left ventricular ejection fraction ≤0.40 and asymptomatic nonsustained ventricular tachycardia.
Our findings demonstrate that within our trial population, clinical factors have limited ability to accurately predict those with inducible sustained ventricular tachycardia. The results suggest directions for future investigations of factors underlying the development of ventricular tachycardias in patients recovering from myocardial infarction.
MUSTT Trial Investigators
The study sites and investigators participating in the MUSTT trial are listed below in descending order by numbers of patients randomized. For each site, the first person listed was the principal investigator.
Michigan Heart, P.C., Ann Arbor, Mich: Lorenzo DiCarlo, Stuart Winston, Deborah Myers; University of Maryland, Baltimore: Michael R. Gold, Stephen Shorofsky, Robert Peters, Deborah Froman, Henry Scott; Arkansas Cardiology Clinic, Little Rock: G. Stephen Greer, Jan Swaim; Temple University Hospital School of Medicine, Philadelphia, Pa: John M. Miller, Alfred E. Buxton, Henry H. Hsia, Steven A. Rothman, Glenn Harper, Lyle Siddoway, Steven Zukerman, Debra Whitley, Cassandra Slater, Mary Gastineau, James Edinger, Debra Ackerman, Nancy Bowe; Northside Cardiology, Inc, Indianapolis, Ind: Eric N. Prystowsky, Joseph Evans, Larry Jacobs, Louis Janeira, Mike Markel, R.I. Fogel; Midwest Heart Research Foundation, Lombard, Ill: Michael F. O’Toole, Elaine Enger; University of Ottawa Heart Institute (Ontario): Anthony Tang, Martin Green, Claire Carey; University of Pennsylvania, Philadelphia: Alfred E. Buxton, Mark E. Josephson, Michael Hanna, Nancy Britton, Kenneth Gephardt, Linda Goffredo; Montefiore Medical Center, Bronx, NY: John D. Fisher, Kevin Ferrick, Soo Kim, J. Roth, Larry Chinitz, Taya Glotzer, Aileen Ferrick, Judy Durkin; Columbia University, New York, NY: James Coromilas, John Zimmerman, James Reiffel, Frank Livelli, Kathleen Hickey; Montreal Heart Institute (Quebec): Mario Talajic, Denis Roy, Marc Dubuc, Danielle Beaudoin, Johanne Marquis; EP Consultants, Detroit, Mich: Michael H. Lehmann, Russell T. Steinman, John J. Baga, Luis A. Pires, Claudio D. Schuger, Debra Frankovich, Julie Fresard; Southern New Hampshire Cardiology Center, Manchester: Bruce Hook, Lois Brown; Cardiology Associates, Johnson City, NY: Nicholas Stamato, Debra Whiting; Tulane University School of Medicine, New Orleans, La: Michael Prior, James Talano, Nancy Wicker; Mayo Foundation, Rochester, Minn: Douglas Packer, Stephen C. Hammil, Carolyn Stevens; Thoracic and Cardiovascular Institute, Lansing, Mich: John H. Ip, Denise Grimes, Terry Magnum, Beth McAndrews; Vanderbilt University, Nashville, Tenn: Debra Echt, Dan Roden, Nancy Conners; New York Medical College, White Plains, NY: David A. Rubin, Carmine Sorbera, Annemarie McAllister; Lancaster Heart Foundation (Pa): Seth Worley, Gary Rubright, Joann Tuzi, Kay Knepper; Hopital du Sacre-Coeur de Montreal (Quebec): Teresa Kus, Reginald Nadeau, Ginette Gaudette, Jocelyne Fouquette; Yale University, New Haven, Conn: William P. Batsford, Craig McPherson, Alice Van Zetta, Ginny Elwood; University of Texas Southwestern Medical Center, Dallas: Richard L. Page, Jose A. Joylar, Gigi Erwin, Lauren Nelson; St Luke’s Hospital, Kansas City, Mo: Robert Lemery, David Steinhaus, Debbie Cardinale; Hoag Memorial Hospital/Presbyterian Medical Center, Newport Beach, Calif: Brian Kennelly, Gloria Mirabal, Kelly Porter; University of Calgary (Alberta): George Wyse, Henry J. Duff, Anne M. Gills, Teresa M. Kieser, L. Brent Mitchell, John M. Rothschild, Robert S. Sheldon, Joy Kellen, Debbie Ritchie, Bonnie Baptie; Audubon Regional Medical Center, Louisville, Ky: James M. Kammerling, Vaughn Payne, Julie Hanrahan; Albany Medical College (NY): Arthur Portnow, Jaggarao Nattama, Daniel O’Dea, Celeste Ocampo, Iona Megas-Nowak; University of Connecticut Health Center, Farmington: Ellison Berns, Mary Beth Barry, Laura Kearney, Patricia Stefanow, Patricia Malone; Mt Sinai Medical Center, New York, NY: J. Anthony Gomes, Stephen L. Winters, Elena Pe; Sentara Norfolk General Hospital (Va): Robert C. Bernstein, John M. Herre, John Onufer, Lauren McGowan, Linette Klevan, Catherine Townsend; University of Massachusetts, Worcester: S.K. Stephen Huang, Robert S. Mittleman, Alan B. Wagshal, Kelly-Ann Rofino, Karen Rofino; Cooper Hospital/University Medical Center, Camden, NJ: Andrea M. Russo, Harvey Waxman, Catherine Stubin, Trudi Meehan; Cardiology Foundation of Lankenau Hospital, Wynnewood, Pa: Peter Kowey, Anne Marie Chikowski, Helga Criner; SUNY Health Science Center, Brooklyn, NY: Nabil El-Sherif, Gioia Turitto, Lenore Knudson; Sutter Institute for Medical Research, Sacramento, Calif: Gearoid O’Neill, Arjun Sharma, Ann Skadsen; Pepin Heart and Vascular Institute, Tampa, Fla: Christian Machado, Stephen Mester, Cindi Sullivan; West Virginia University, Morgantown: Stanley B. Schmidt; Cardiac Disease Specialists, Atlanta, Ga: Thomas Deering, Shelley Holt; Rockford Electrophysiology Consultants (Ill): Mark Hiser, Thong Pham, Eugene Silva, Peg Dittmar; Iowa Heart Center, Des Moines: W. Ben Johnson, Mickey Core-Bier, Teresa Coulson; Rhode Island Hospital, Providence: Robert Lemery, Eric Berger, Chester A. Chmielewski, Emily Connolly; Presbyterian Hospital of Dallas (Tex): Jodie Hurwitz, Brenda Wimberly, Dee Dee Capper; VA Medical Center, Washington, DC: Steven Singh, Ross Fletcher, Raymond Woosley, Deborah Byrns, Barbara Bennett; Duke University Medical Center, Durham, NC: Ruth Ann Greenfield, Helen Daniels, Cathy Grill; University of Louisville School of Medicine (Ky): Igor Singer, Shannon Blair, Aida Cicic; University of Nebraska Medical Center, Omaha: John Windle, William Barington, Arthur Easley, Laura Smith; Beth Israel Hospital–Boston (Mass): Mark E. Josephson, Roxellen Bayer, Vicki Schreckengost; Washington University, St Louis, Mo: Michael E. Cain, Judy Osborn; Sinai Hospital of Baltimore (Md): Joseph Reilly, D.J. Schamp, Vicki O’Mara; Maine Medical Center, Portland: Joel Cutler, John Love, Claire Berg; Medical Center Hospital of Vermont, Burlington: Mark A. Capeless, Michaelanne Rowen; Virginia Commonwealth University, Richmond: Mark Wood, Ken Ellenbogen, Bruce Stambler, Robert Sperry, Michael Belz, Virginia Gillock, Cheryl Dietrich, Nancy Michaels, Donna Sargent; Cardiology of Tulsa, Inc, (Okla): John Swartz, David W. Frazier, Wayne O. Adkisson, R. Douglas Ensley, Sheila Dewald, Lonna Klahr; Riverside Regional Medical Center, Newport News, Va: Allan Murphy, Sheila Gessner, Marilyn Barton, Loretta Heezen; Illinois Masonic Medical Center, Chicago: Richard Kehoe, Sharon Crandall, Liz Farwell; The University of Alabama at Birmingham: Sharon Dailey, Rosemary Bubien, Charlie Tidwell; St Francis Medical Center, Pittsburgh, Pa: Andres Ticzon, Carol DiGiocomo, Louise Predis; University of New Mexico HSC, Albuquerque: Gary M. Greenberg, Renzo M. Cataldo, Tracy Hudson, Lorena Beeman; VA Medical Center, Ann Arbor, Mich: William Kou, Debbie Randall; University of Florida, Gainesville: Anne B. Curtis, Michelle Mardis, Maureen LaTour; Staten Island University Hospital (NY): Soad Bekheit-Saad, Mary Lynn Brezsnyak, Ann V. Porter, Helen Walsh; North Shore University Hospital, Manhasset, NY: Ram Jadonath, Todd Cohen, Bruce Goldner, Donna Kalenderian, Lisa Chepurko; Heart Center, Sarasota, Fla: Walter Hepp, Mary Healy, Holly Taylor; Wichita Institute for Clinical Research (Kan): Gioia Turitto, Jesus E. Val-Mejias, Demo Klonis, Pat Patterson; St Vincent Medical Center, Toledo, Ohio: Sheldon Brownstein, Vuong Duthinh, Joyce Morris, Ron Oberhaus; Clearwater Cardiovascular Consultants, Largo, Fla: Jose Gallastegui, Kaye Livingston; Medical Center of Delaware, Newark: Henry Weiner, Raymond Vitullo, Angela DiSabitino, Sherry Feehs; University of Virginia Medical School, Charlottesville: John DiMarco, Stacy Thompson; The New York Hospital–Cornell Medical Center, New York, NY: Bruce Lerman, Melissa Sarmiento; Cardiology Care Specialists, Allentown, Pa: Luis Constantin, Claire Kern, Cheryl Fedak; University of Pittsburgh (Pa): Kelley Anderson, Stephen Fahrig, Barb Miklo; Robert Wood Johnson Medical School, New Brunswick, NJ: Mark Preminger, Nora Cosgrove; Carle Clinic Association, Urbana, Ill: Abraham Kocherill, Jean Shane, Sylvia Lofrano; Mid Florida Cardiology Specialists, Orlando: Marcos Hazday, Libby Jopperi; Harper Hospital, Detroit, Mich: Marc B. Meissner; St Paul Ramsey Medical Ctr (Minn): Pablo Denes, Lyle Swenson, Cathy Vittum; Medical College of Pennsylvania and Hahnemann University, Philadelphia: David J. Callans, Francis E. Marchlinski, Charles D. Gottlieb, Christine Vrabel; Rush Presbyterian/St Luke’s Medical Center, Chicago, Ill: Raman Mitra, Richard Trohman, Luz Maria Remiz-Morgen, Patty Rapnikas; Central Baptist Hospital, Lexington, Ky: Michael Rukavina, Kathy Tincher; Heart Clinics Northwest, Spokane, Wash: Timothy Lessmeir, Jan Priggee, Debbie Westover; University of Colorado Health Sciences Center, Denver: Patricia Kelly, Theresa Heyborne; Heart Care Midwest, S.C., Peoria, Ill: Robert Bauernfeind, Frank L. Gold, Tammy Wall.
This study was supported by grants UO1-HL45700 and UO1-HL45726 from the National Heart, Lung, and Blood Institute, National Institutes of Health, and by grants from C.R. Bard, Inc, Berlex Laboratories, Inc, Boehringer-Ingelheim Pharmaceuticals, Inc, Cardiac Pacemakers, Inc/Guidant, Knoll Pharmaceutical Co, Medtronic, Inc, Merck, Searle Pharmaceutical, Ventritex, and Wyeth-Ayerst Laboratories.
A complete list of investigators can be found in the Appendix.
- Received June 17, 1998.
- Revision received December 31, 1998.
- Accepted January 11, 1999.
- Copyright © 1999 by American Heart Association
Tavazzi L, Volpi A, the GISSI Investigators. Remarks about postinfarction prognosis in light of the experience with the Gruppo Italiano per lo Studio della Sopravvivenza nell’ Infarto Miocardico (GISSI) Trials. Circulation. 1997;95:1341–1345.
Daly L, Hickey N, Graham I, Mulcahy R. Predictors of sudden death up to 18 years after a first attack of unstable angina or myocardial infarction. Br Heart J. 1987;58:567–571.
Rouleau JL, Talajic M, Sussex B, Potvin L, Warnica W, Davies RF, Gardner M, Stewart D, Plante S, Dupuis R, Lauzon C, Ferguson J, Mikes E, Balnozan V, Savard P. Myocardial infarction patients in the 1990s: their risk factors, stratification and survival in Canada: the Canadian Assessment of Myocardial Infarction (CAMI) Study. J Am Coll Cardiol. 1996;27:1119–1127.
Richards DAB, Byth K, Ross DL, Uther JB. What is the best predictor of spontaneous ventricular tachycardia and sudden death after myocardial infarction? Circulation. 1991;83:756–763.
Bourke JP, Richards ADB, Ross DL, Wallace EM, McGuire MA, Uther JB. Routine programmed electrical stimulation in survivors of acute myocardial infarction for prediction of spontaneous ventricular tachyarrhythmias during follow-up: results, optimal stimulation protocol and cost-effective screening. J Am Coll Cardiol. 1991;18:780–788.
Buxton AE, Lee KL, DiCarlo L, Echt DS, Fisher JD, Greer GS, Josephson ME, Packer D, Prystowsky EN, Talajic M, for the Multicenter Unsustained Tachycardia Trial Investigators. Nonsustained ventricular tachycardia in patients with coronary artery disease: relationship to inducible sustained ventricular tachycardia. Ann Intern Med. 1996;125:35–39.
Prystowsky EN, Buxton AE, Lee K, Coromilas J, Tang AS, Hafley G. Nonsustained ventricular tachycardia characteristics: do they correlate with cardiac function and sustained ventricular tachycardia? Circulation. 1997;96(suppl I):I-334. Abstract 1861.
Buxton AE, Fisher JD, Josephson ME, Lee KL, Pryor DB, Prystowsky EN, Simson MB, DiCarlo L, Echt DS, Packer D, Greer GS, Talajic M, and the MUSTT Investigators. Prevention of sudden death in patients with coronary artery disease: the Multicenter Unsustained Tachycardia Trial (MUSTT). Prog Cardiovasc Dis. 1993;36:215–226.
Smith PL. Splines as a useful and convenient statistical tool. Am Statistician. 1979;33:57–62.
Harrell FE Jr, Lee KL, Pollack BG. Regression models in clinical studies: determining relationships between predictors and response. J Natl Cancer Inst. 1988;80:1198–1202.
Dubey RK, Gillespie DG, Jackson EK, Keller PA. 17β-Estradiol, its metabolites, and progesterone inhibit cardiac fibroblast growth. Hypertension. 1983;31(part 2):522–528.
Buxton AE, Marchlinski FE, Flores BT, Miller JM, Doherty JU, Josephson ME. Nonsustained ventricular tachycardia in patients with coronary artery disease: role of electrophysiologic study. Circulation. 1987;75:1178–1185.
Gomes JAC, Hariman RI, Kang PS, El-Sherif N, Chowdhry I, Lyons J. Programmed electrical stimulation in patients with high-grade ectopy: electrophysiologic findings and prognosis for survival. Circulation. 1984;70:43–51.
Kadish A, Schmaltz S, Calkins H, Morady F. Management of nonsustained ventricular tachycardia guided by electrophysiological testing. PACE. 1993;16:1037–1050.
Wilber DJ, Olshansky B, Moran JF, Scanlon PJ. Electrophysiological testing and nonsustained ventricular tachycardia: use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation. 1990;82:350–358.
Kersschot IE, Brugada P, Ramentol M, Zehender M, Waldecker B, Stevenson WG, Geibel A, DeZwaan C, Wellens HJ. Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: a prospective, randomized study. J Am Coll Cardiol. 1986;7:1234–1242.
Roy D, Marchand E, Theroux P, Waters DD, Pelletier GB, Bourassa MG. Programmed ventricular stimulation in survivors of an acute myocardial infarction. Circulation. 1985;72:487–494.
Waspe LE, Seinfeld D, Ferrick A, Kim SG, Matos JA, Fisher JD. Prediction of sudden death and spontaneous ventricular tachycardia in survivors of complicated myocardial infarction: value of the response to programmed stimulation using a maximum of three ventricular extrastimuli. J Am Coll Cardiol. 1985;5:1292–1301.
Iesaka Y, Nogami A, Aonuma K, Nitta J, Chun Y, Fujwara H, Hiraoka M. Prognostic significance of sustained monomorphic ventricular tachycardia induced by programmed ventricular stimulation using up to triple extrastimuli in survivors of acute myocardial infarction. Am J Cardiol. 1990;65:1057–1063.
Denniss AR, Richards DA, Cody DV, Russell PA, Young AA, Cooper MJ, Ross DL, Uther JB. Prognostic significance of ventricular tachycardia and fibrillation induced at programmed stimulation and delayed potentials detected on the signal-averaged electrocardiograms of survivors of acute myocardial infarction. Circulation. 1986;74:731–745.