Cardiac Resynchronization Therapy in CHF Who and When
SPECIAL REPORT
By Harold L. Karpman, MD
Clinical Professor of Medicine, UCLA School of Medicine
Disclosure; Dr. Karpman reports no financial conflicts of interest in this field of study.
Despite the recent explosion of pharmacologic agents available for the treatment of congestive heart failure (CHF), many patients continue to be severely symptomatic and their prognosis remains poor.
Cardiac dyssynchrony is commonly noted in these
patients because of altered timing of myocardial contractions primarily due to intraventricular conduction
defects.1,2 The COMPANION trial reported that car-
diac resynchronization therapy (CRT) alone or combined with an implantable defibrillator reduced the composite end point of death from any cause or hospitalization during a mean follow-up of 16
months,3 however, the decrease in the risk of death was not significant with CRT alone.
Because meta-analysis studies4,5 have not clarified the issues, Cleland and associates enrolled 813 New York Heart Association class III and IV CHF patients who were followed for a mean of 29.4 months and who were randomly assigned to receive medical therapy alone or with CRT (ie, the Cardiac Resynchronization-Heart Failure [CARE-HF] trial).11 The primary end point was the time to death from any cause or an unplanned hospitalization for a major cardiovascular event, and the principal secondary end point was death from any cause. Compared with medical therapy, CRT reduced the interventricular mechanical delay, the endsystolic volume index, and the area of the mitral regurgitant jet. In addition, CRT increased the left ventricular ejection fraction, improved the quality of life and reduced symptoms in a statistically significant way.
Finally, CRT significantly reduced the incidence of time to death or to an unplanned hospitalization for a major cardiovascular event and significantly reduced mortality from all causes.
Commentary
Since 25-33% of all CHF patients have dyssynchronous electrical activation due to some form of an intraventricular conduction abnormality,6,7 dyssynchronous contractions will occur and will result in both reduced ejection fractions and cardiac outputs. Conventional right ventricular pacing actually impairs ventricular function by producing an artificially induced intraventricular conduction delay even in patients without heart failure.8 CRT simultaneously paces both ventricles (ie, biventricular pacing) and, in fact, since many of the patients who are appropriate candidates for cardiac-resynchronization therapy are also candidates for implantation of a cardioverter-defibrillator, newer integrated devices capable of performing both functions are now available. However, since cardiac resynchronization alone appears to so substantially reduce the risk of decompensation and death among patients with moderate or severe CHF and since only a small number of patients (7%) receiving CRT died suddenly, a defibrillator might further reduce the risk of sudden death but only minimally.9,10
Preventing and even reversing the progression of cardiac dysfunction with CRT appears to be an excellent method for significantly reducing the incidence of malignant arrhythmias in patients with CHF and may be a better therapeutic approach than simply treating the arrhythmia with an implanted defibrillator once it occurs. However, the beneficial effects of CRT therapy on mortality are gradual and probably due to the effects of reverse ventricular remodeling whereas the beneficial effects of defibrillator therapy obviously are quite immediate. Since it may take time for the protective effect of CRT to become effective, at the present time it would appear more desirable to implant a combined device (ie, cardiac resynchronization-defibrillator) at the outset. A trial comparing biventricular pacing with and without the use of an implantable cardioverter-defibrillator should be performed however, since even the small number of deaths in the CARE-HF trial would probably have been prevented by a defibrillator it may prove to be ethically difficult to mount such a trial. Therefore, for the time being, a combined unit should be recommended for patients with NYHA class IV CHF but it should be recognized that the data from CARE-HF11 does provide support for the implantation of the less expensive CRT device alone in those patients who are willing to accept the tiny residual risk of sudden cardiac death and who desire a form of therapy which has been demonstrated to improve quality of life and longevity without the risk of inappropriate painful shocks (ie, due to supraventricular tachycardias or device malfunction) which may be produced by a defibrillator unit.
References
1. Khand A, et al. Is the prognosis of heart failure improving? J Am Coll Cardiol. 2000;36:2284-2286.
2. Cleland JGF, Clark AL. Delivering the cumulative benefits of triple therapy to improve outcomes in heart failure: too many cooks will spoil the broth. J Am Coll Cardiol. 2003;42:1234-1237.
3. Bristow MR, et al. Cardiac-resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. 2004;350:2140-2150.
4. McAlister FA, et al. Systematic review: cardiac resynchronization in patients with symptomatic heart failure. Ann Intern Med. 2004;141:381-390.
5. Calvert M, et al. Cardiac resynchronization therapy in heart failure. Ann Intern Med. 2005;142:305-307.
6. Shamim W, et al. Intraventricular conduction delay: a prognostic marker in chronic heart failure. Int J Cardiol. 1999;70:171-178.
7. Farwell D, et al. How many people with heart failure are appropriate for biventricular resynchronization? Eur Heart J. 2000;21:1246-1250.
8. Sweeney MO, et al. Adverse effect of ventricular pacing on heart failure and atrial fibrillation among patients with normal baseline QRS duration in a clinical trial of pacemaker therapy for sinus node dysfunction. Circulation. 2003;107:2932-2937.
9. Bardy GH, et al. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. N Engl J Med. 2005;352:225-237.
10. Cleland JF, et al. Clinical trials update and cumulative meta-analyses from the American College of Cardiology. Eur J Heart Fail. 2004;6:501-508.
11. Cleland JF, et al for the Cardiac Resynchronization-Heart Failure (CARE-HF) Study Investigators. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005;352:1539-1549.
By Harold L. Karpman, MD Clinical Professor of Medicine, UCLA School of Medicine Disclosure; Dr. Karpman reports no financial conflicts of interest in this field of study. Despite the recent explosion of pharmacologic agents available for the treatment of congestive heart failure (CHF), many patients continue to be severely symptomatic and their prognosis remains poor.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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