Sudden Cardiac Death in Cardiomyopathy
Abstract & Commentary
Synopsis: The surprisingly low mortality in the patient population prevented their ability to demonstrate any benefit of ICD therapy in this group.
Source: Bansch D, et al. Circulation. 2002;105: 1453-1458.
Bansch and coworkers from germany report the results of a trial of ICD therapy in patients with nonischemic dilated cardiomyopathy (DCM). Patients were eligible for inclusion if they were between 18 and 70 years of age, had recent onset (less than or equal to 9 months), symptoms due to nonischemic DCM, and a left ventricular ejection fraction (LVEF) less than or equal to 30%. Patients had to be in New York Heart Association functional class II or III. Patients who had a history of symptomatic bradycardia or ventricular arrhythmias or those who were listed for heart transplantation were excluded. All patients underwent physical examination, baseline ECG, exercise testing, and echocardiography. Each patient underwent a 24-hour ambulatory ECG and an electrophysiologic study to determine if ventricular arrhythmias were inducible. Patients were then randomized to either receive standard therapy or insertion of an implantable cardioverter defibrillator (ICD). Patients who received an ICD had a VT/VF detection zone programmed to 200 bpm. Patients were followed every 3 months.
The pretrial estimate for mortality in this group was 30% in the first year with 40% of these deaths being sudden. The study planned to enroll 1348 patients. After 1 year of follow-up, an interim blinded survival analysis was performed. This indicated that the overall 1-year mortality was only 5.6%. At this point, randomization was stopped due to futility and the patients were then followed throughout an additional 5.5 ± 2 years.
Between July 1991 and March 1997, 104 patients were enrolled in the trial with 50 randomly assigned to ICD treatment and 54 to the control group. The group was 80% male with a mean age of 52 ± 11 years. Two thirds of the patients were in NYHA class II and one third in NYHA class III. The mean ejection fraction (EF) was 24 ± 7%. On a baseline 24-hour Holter monitor, 53% of the patients had nonsustained ventricular tachycardia (VT). Electrophysiologic study induced monomorphic VT in 3 patients and inducible ventricular fibrillation in 10 patients. Ninety-six percent of the patients received an ACE inhibitor. Only a few patients (3.8%) received a beta blocker.
All-cause mortality rates did not differ between the ICD group and the control group after either 1 year (the primary end point) nor after long-term follow-up. After a mean follow-up of 5.5 ± 2 years, 13 patients in the ICD group and 17 in the control group died. Cumulative survival was 92%, 86%, and 73% in the ICD group vs. 93%, 80%, and 68% in the control group after 2, 4, and 6 years, respectively (log rank, P = 0.554). Total mortality was highest in those with an EF less than or equal to 21%, intermediate for those with an EF of 22-27%, and lowest for those with an EF greater than or equal to 28%. There were 11 patients who received ICD therapy for VT greater than 200 bpm. Survival in these was diminished compared to those who had no VT documented.
Bansch et al conclude that the surprisingly low mortality in the patient population prevented their ability to demonstrate any benefit of ICD therapy in this group.
Comment by John P. DiMarco, MD, PhD
The study by Bansch et al provides an interesting look at ICD therapy as primary prevention of sudden death in patients with idiopathic DCM. There are now 2 randomized trials of primary ICD therapy in patients with ischemic cardiomyopathy that have shown benefit among those randomized to receive an ICD. In both the Multicenter Automatic Defibrillator Implantation trial (MADIT) and its follow-up MADIT II, a significant improvement in survival was seen after ICD implantation. The cardiomyopathy trial reported here suggests that as much benefit may not be seen in patients with idiopathic dilated cardiomyopathy. Two other studies are now underway that also address this question. The Sudden Cardiac Death-Heart Failure trial enrolled patients with both ischemic and nonischemic cardiomyopathy. This trial which enrolled 2500 patients is still in the follow-up phase. Another study, the DEFINITE trial, has enrolled more than 400 patients with nonischemic cardiomyopathy. This trial also continues in follow-up. Another study, the AMIOVIRT trial from the University of Michigan, has presented a preliminary report showing no improvement with ICD therapy vs. amiodarone therapy in nonischemic cardiomyopathy.
Why should the defibrillator work in ischemic cardiomyopathy but not in dilated cardiomyopathy? The most obvious reason is that therapy for dilated cardiomyopathy has improved dramatically in the last few years. The widespread use of ACE inhibitors, beta blockers, and other interventions has lowered the overall mortality in dilated cardiomyopathy with many deaths now occurring in the terminal stages of hemodynamic deterioration. Amiodarone may also be more effective in patients with nonischemic cardiomyopathies as opposed to those with ischemic cardiomyopathy. Both the GESICA trial and the CHF-STAT trial reported decreased mortality with amiodarone therapy in patients with nonischemic cardiomyopathy. If amiodarone even produces a relatively small benefit, it will be difficult to show benefit from ICD therapy in DCM patients except in a large trial.
This paper also highlights one of the difficulties in planning large-scale mortality trials. Survival estimates made during the planning phase of a trial will often change as therapy for the underlying condition improves. If effective therapy is added, this will lower the event rate and may make it more difficult or impossible to show benefit from the intervention under study.
Dr. DiMarco is Professor of Medicine, Division of Cardiology, University of Virginia, Charlottesville.