Correspondence

Prophylactic Use of Implanted Cardiac Defibrillators in Patients at High Risk for Ventricular Arrhythmias after Coronary-Artery Bypass Graft Surgery

N Engl J Med 1998; 338:1227-1228April 23, 1998

Article

To the Editor:

In their well-conducted trial, Bigger et al. (Nov. 27 issue)1 found no evidence of improved survival among patients with a depressed left ventricular ejection fraction and an abnormal signal-averaged electrocardiogram in whom a defibrillator had been implanted prophylactically at the time of coronary-artery bypass graft (CABG) surgery. The authors offer several explanations for their observation, including the possible beneficial effect of coronary bypass surgery on the autonomic nervous input to the heart.

It has become increasingly clear that the autonomic nervous system is important in the pathogenesis of ventricular arrhythmias and sudden death from cardiac causes. Heightened sympathetic activity has been shown to favor the development of cardiac arrhythmias, whereas increased vagal tone is thought to have a protective effect.2 There are several methods of assessing the autonomic nervous system; one of the most extensively used approaches in clinical practice is the determination of the variability of the heart rate, which has been shown to be a noninvasive marker of autonomic, parasympathetic input to the heart.2 Kleiger et al.3 reviewed Holter-monitor recordings from 808 patients enrolled in the Multicenter Postinfarction Research Group study. Of all Holter variables measured, heart-rate variability had the strongest univariate correlation with mortality. Heart-rate variability remained a significant predictor of mortality after adjustment for clinical variables, demographic variables, other features of the Holter recordings, and ejection fraction.

To date, only a few studies have assessed the effect of coronary bypass surgery on heart-rate variability. Niemela et al.4 found that in 35 patients, six weeks after coronary-artery bypass surgery, all spectral components of heart-rate variability were significantly attenuated. In contrast, in a recent report, Bellwon et al.5 noted a significant increase in the high-frequency component of heart-rate variability six weeks after coronary-artery bypass surgery, suggesting that vagal tone increased after coronary blood flow improved. The results reported by Bigger et al.1 may be attributed at least in part to the cardioprotective effect of surgical revascularization on the autonomic nervous system, an effect that could have been assessed by determining preoperative and postoperative heart-rate variability.

Oren Fruchter, M.D.
29 Greenbaum St., Haifa 34987, Israel

5 References

1. 1

   Bigger JT Jr. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. N Engl J Med 1997;337:1569-1575
   Full Text | Web of Science | Medline

2. 2

   Barron HV, Lesh MD. Autonomic nervous system and sudden cardiac death. J Am Coll Cardiol 1996;27:1053-1060[Erratum, J Am Coll Cardiol 1996;28:286.]
   CrossRef | Web of Science | Medline

3. 3

   Kleiger RE, Miller JP, Bigger JT Jr, Moss AJ. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol 1987;59:256-262
   CrossRef | Web of Science | Medline

4. 4

   Niemela MJ, Airaksinen KE, Tahvanainen KU, Linnaluoto MK, Takkunen JT. Effect of coronary artery bypass grafting on cardiac parasympathetic nervous function. Eur Heart J 1992;13:932-935
   Web of Science | Medline

5. 5

   Bellwon J, Siebert J, Rogowski J, et al. Heart rate power spectral analysis in patients before and 6 weeks after coronary artery bypass grafting. Clin Sci 1996;91:Suppl:19-21
   Medline

To the Editor:

In the CABG Patch Trial, Bigger et al. underestimated the importance of relieving ischemia in explaining their results. Since signal-averaged electrocardiographic abnormalities are good markers for ventricular arrhythmias, albeit their positive predictive value is low,1 it follows that normalization of these abnormalities may reduce the risk of ventricular arrhythmias and sudden death. It is also known that patients without signal-averaged electrocardiographic abnormalities have a better prognosis than those with such abnormalities. Thrombolytic therapy and percutaneous transluminal coronary angioplasty have been reported to improve abnormalities in the signal-averaged electrocardiogram in some patients,2 thereby possibly reducing the potential for serious ventricular arrhythmias. The same may be true for surgical revascularization.

There was no mention of whether follow-up signal-averaged electrocardiograms were obtained to see whether the abnormalities had resolved or improved. If there was improvement, the lack of difference in survival benefit between the two groups may be explained by the beneficial effect of CABG surgery, which all patients in the trial underwent.

The conclusions drawn in the CABG Patch Trial could be modified as follows: surgical revascularization in patients with coronary heart disease, a depressed left ventricular ejection fraction, and an abnormal signal-averaged electrocardiogram may obviate the need for the implantation of a defibrillator.

F.A.E. Suliman, M.R.C.P.
King Saud University College of Medicine, Abha 11421, Saudi Arabia

2 References

1. 1

   Kjellgren O, Gomes JA. Current usefulness of the signal-averaged electrocardiogram. Curr Probl Cardiol 1993;18:361-418
   CrossRef | Web of Science | Medline

2. 2

   Manolis AS, Katsaros C, Foussas S, Olympios C, Fakiolas C, Cokkinos DV. Effect of successful coronary artery angioplasty on the signal-averaged electrocardiogram. Pacing Clin Electrophysiol 1992;15:950-956
   CrossRef | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: The CABG Patch Trial did not demonstrate any survival benefit of prophylactic implantation of cardioverter–defibrillators in high-risk patients with coronary heart disease who were undergoing CABG surgery. The Multicenter Automatic Defibrillator Implantation Trial (MADIT)1 reported a 50 percent reduction in the mortality rate after treatment with an implantable cardioverter–defibrillator in patients whose cardiovascular disease was similar in terms of causes and severity to that in our patients2 but in whom ventricular tachyarrhythmias were induced during electrophysiologic testing. We hypothesized that the difference in the results of the two trials stemmed from the fact that we had a low percentage of patients with inducible ventricular tachycardia. Alternatively, we hypothesized that CABG surgery decreased the frequency of arrhythmic events during follow-up, as suggested by Dr. Suliman.

We are conducting an electrophysiologic substudy to determine which of these two hypotheses is true. Surviving patients will receive programmed ventricular stimulation to determine the prevalence of inducible sustained ventricular tachycardia. In order to explain the lack of improvement in survival in our trial on the basis of a low proportion of patients with inducible ventricular tachycardia despite the presence of a relative risk for such patients that was similar to that in MADIT,3 we calculate that fewer than 25 percent of the patients would have had to have inducible ventricular tachycardia at the time of randomization.4 The percentage of patients with inducible ventricular tachycardia at the time of randomization can be calculated with use of the results of the electrophysiologic test, the existing survival data, and subsequent follow-up data.

If more than 25 percent of the patients had inducible ventricular tachycardia, then the relative risk (calculated as the mortality rate among the patients with inducible ventricular tachycardia divided by the mortality rate among patients with noninducible ventricular tachycardia) in our trial would have to have been substantially lower than the relative risk in MADIT, indicating that surgical revascularization had a dominant role in reducing lethal tachyarrhythmic events in the presence of a substrate for arrhythmia, a finding that would support Dr. Suliman's hypothesis.

If evidence of a benefit from CABG surgery is found in the electrophysiologic substudy, a favorable effect on the autonomic nervous system could be an important mechanism for the surgery-related benefit, as suggested by Dr. Fruchter. We will determine the effect of CABG surgery on heart-rate variability by analyzing preoperative and postoperative Holter electrocardiographic recordings.

J. Thomas Bigger, Jr., M.D.
Columbia University College of Physicians and Surgeons, New York, NY 10032

John P. DiMarco, M.D., Ph.D.
University of Virginia School of Medicine, Charlottesville, VA 22908

Jeffrey N. Rottman, M.D.
Vanderbilt University School of Medicine, Nashville, TN 37232

4 References

1. 1

   Moss AJ, Hall WJ, Cannom DS, et al. Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. N Engl J Med 1996;335:1933-1940
   Full Text | Web of Science | Medline

2. 2

   Curtis AB, Cannom DS, Bigger JT Jr, et al. Baseline characteristics of patients in the Coronary Artery Bypass Graft (CABG) Patch Trial. Am Heart J 1997;134:787-798
   CrossRef | Web of Science | Medline

3. 3

   Daubert JP, Higgins SL, Zareba W, Wilber DJ. Comparative survival of MADIT-eligible but noninducible patients. J Am Coll Cardiol 1997;29:Suppl A:78A-78A abstract.
   CrossRef

4. 4

   Rottman JN, Levin B, Parides M, Steinman RC, Bigger JT Jr. A “mixture model” can explain the difference between outcomes in the MADIT and CABG Patch Trials. Pacing Clin Electrophysiol (in press).