The most devastating and common cause of death after acute myocardial infarction is sudden cardiac death, generally due to ventricular tachyarrhythmias. The likelihood of sudden cardiac death is variable, and can be predicted by a number of risk factors. In the convalescent phase of MI, chronic beta-blocker therapy is the only pharmacologic intervention that has been demonstrated to reduce sudden cardiac death risk.
In 1996, for the first time, it was demonstrated in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) that prophylactic insertion of an implantable cardioverter defibrillator (ICD) could reduce the risk of death, by approximately 50%, in selected high-risk patients. Patients were eligible after MI if ejection fraction was 35% or less, if nonsustained VT was seen on an ECG recording, and if sustained VT was induced at EPS.
The presence of extensive scar, as manifested by severe left ventricular dysfunction, may overwhelm other prognostic tests and make it difficult to predict which of these patients would benefit from prophylactic ICD. With these considerations, MADIT II was designed and implemented. The results were reported recently.
Patients were eligible to participate in MADIT II if the LVEF was < 30% in patients with prior MI. Patients were at least three months since their last revascularization procedure. 1232 patients were enrolled and randomized to receive ICD or be treated with conventional medical therapy including beta-blockers, ACE inhibitors, and aspirin.
Clinical characteristics were similar between the two randomized groups. Patients were characterized by severe left ventricular dysfunction with an EF of 23%.
Benefit Shown with ICD Treatment
Follow-up averaged 20 months. The trial was stopped abruptly when there was clear-cut evidence of benefit for the ICD- treated patients. There was a 31% reduction in the risk of death in the ICD group compared to the conventional therapy group. The overall mortality rate was nearly 20% for the conventional therapy group versus approximately 14% for the ICD treated group.
A recently presented abstract indicated that virtually all of the reduction in death was due to a decrease in sudden death in the ICD group. Further, the risk of sudden death was reduced very early in follow-up and progressively increased over time. Additional analyses indicated that all of the prespecified and post-hoc subgroups that were tested demonstrated benefit with ICD treatment. For example, patients benefited regardless of age, EF, time since MI, underlying rhythm, etc.
There was an interesting relationship between baseline QRS duration and response to randomized therapy. There seemed to be a slight trend for greater benefit in patients with a prolonged QRS duration compared to those with a normal QRS duration, but the confidence intervals were quite wide and the subgroups were small in size so that no definite conclusions could be drawn.
Does RV Pacing Increase Risk?
Another interesting trend was observed during follow-up. There was an increased risk of new or worsened heart failure in the ICD group versus the conventional therapy group, 19.9% vs. 14.9 %, during the trial (p=0.1). The explanation for this potential increased hazard was initially uncertain.
A recent presentation led by our center was presented as a Late-Breaking Clinical Trial at the 2003 NASPE Scientific Sessions. Analysis of the MADIT II data indicated that in patients who had > 50% of cumulative right ventricular pacing, there was a substantially increased risk of developing new or worsened heart failure, cardiac death, or ICD therapy for VT/VF. The presence of right ventricular pacing was independently predictive of these morbid or fatal outcomes. Thus, this is a potential explanation for the increased hazard for heart failure observed in the ICD group in the MADIT II.
These results are consistent with other recent studies that suggest that a high prevalence of right ventricular pacing can induce deleterious functional consequences in vulnerable patients and should be avoided at all costs. RV pacing generates left bundle branch block and alters the ventricular contraction sequence resulting in substantial acute and chronic hemodynamic consequences.
Alternative programming on the ICD should be employed to avoid chronic ventricular pacing if patients do not have a significant bradycardic need that specifically requires AV or ventricular pacing. Please consult with our group if you have any questions regarding device programming.
Guidelines for ICD Implantation
The FDA had previously granted manufacturers an indication for ICD implantation in all patients with prior MI and LVEF 30% or less (i.e. MADIT II). In addition, the ACC/AHA/NASPE formally created a Class II A indication for ICD implantation in the same MADIT II patients. Finally, the Centers for Medicare and Medicaid Services has recently approved ICD implantation for patients with a prior MI and LVEF 30% or less but only in the presence of a QRS duration greater than 120 milliseconds.
In conclusion, the ICD saves lives in patients with coronary heart disease and left ventricular dysfunction. We recommend screening all inpatients and outpatients for the clinical characteristics described above. Patients are eligible to receive an ICD regardless of the length of time since their prior MI (but at least one month). Patients with congestive heart failure refractory to medications who have a prolonged QRS duration, may also be eligible for a biventricular ICD.
References:
Moss, A.J., Hall, W.J., Cannom, D. S., Daubert, J. P., Higgins, S. L., Klein, H., Levine, J. H., Saksena, S., Waldo, A. L., Wilber, D., Brown, M. W., Heo, M.
Improved Survival With an Implanted Defibrillator in Patients with Coronary Disease at High Risk for Ventricular Arrhythmia.
N Engl J Med
1996; 26:1933-40.
Moss, A. J., Zareba, W., Hall, W. J., Klein, H., Wilber, D., Cannom, D., Daubert, J., Higgins, S. L., Brown, M., Andrews, M.
Prophylactic Implantation of a Defibrillator in Patients with Myocardial Infarction and Reduced Ejection Fraction.
N Engl J Med
2002; 12:877-83.
Steinberg, J. S., Maniar, P., Zareba, W., Wang, P., Schuger, C., Daubert, J., Andrews, M., Brown, M., Moss, A. J. for the MADIT-II investigators.
The Relationship of Right Ventricular Pacing and Outcome in the MADIT-II Patients.
Presented at NASPE 2003 as Late Breaking Clinical Trial.
Reproduced with permission. Published by the Arrhythmia Service of St. Luke's-Roosevelt
Hospital Center, New York, New York.
Volume 9, Issue 4
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