A primary goal in the treatment of heart failure is to extend the life of the patient. Patients with left ventricular dysfunction, with or without the clinical signs and symptoms of heart failure, usually die as a consequence of either progressive heart failure (progressive pump dysfunction) or sudden cardiac death (usually a ventricular arrythmia).

To optimize outcomes in left ventricular dysfunction or heart failure, cardiologists must reduce both morbidity and mortality related to both causes of death. Clinical trial data show that cardiac resynchronization therapy (CRT) can confer a survival benefit. However, the weight of evidence suggests that CRT reduces mortality related to progressive pump failure, but not sudden cardiac death.

Clinical trials of resynchronization therapy have evaluated a variety of measures, including quality of life, functional status and exercise capacity, remodeling parameters, and morbidity and mortality.

In more than 12 trials including a total of more than 4,000 patients CRT consistently improves quality of life and functional status. The concordance of the data is striking, with marked improvements in the Minnesota Living with Heart Failure quality of life score, and significant improvements in New York Heart Association functional class. This is also true for the effect of CRT on exercise capacity. Investigations show a consistent pattern of improvement in peak VO₂ and exercise capacity.

Furthermore, CRT appears to have an effect on the natural history of disease. Dr. Abraham and colleagues recently published results of the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. While they powered the study to evaluate functional endpoints, the researchers did show that CRT improved measures of heart failure morbidity, and in the combined endpoint of death or worsening heart failure requiring hospitalization.

However, these results do not tell the entire story. A recently published meta-analysis extends the observations of the MIRACLE trial. Researchers demonstrated a 51% reduction in the risk of death due to progressive heart failure. However, they found that CRT did not reduce mortality unrelated to heart failure. In fact, they found a trend toward increased mortality. Dr. Abraham said this shows that the gains occurred in reductions on heart failure mortality, but not sudden cardiac death.

There are now numerous trials on the use of ICDs in patients with left ventricular dysfunction or heart failure. Predominantly, these trials include patients with ischemic heart disease. The exclusion of patients with nonischemic cardiomyopathy is a limitation. However, Dr. Abraham argued that there are now compelling data in both groups of patients that combined CRT and ICD is beneficial for both groups.

The landmark Multicenter Automatic Defibrillator Implantation Trial-II (MADIT II) trial may be the paradigm for use of prophylactic ICDs in patients with left ventricular dysfunction or heart failure. In patients with ischemic heart failure, and left ventricular ejection fraction less than or equal to 30%, there was a reduction in all-cause mortality of approximately 31%. Dr. Abraham said these study results are very good news for patients.

All subgroups in MADIT II benefited equally well from the ICD. Notably, subgroup analysis suggested that patients with wider QRS complexes had greater benefit.

However, ICDs primarily reduce mortality due to sudden cardiac death, Dr. Abraham said. They do not appear to alter the natural history of heart failure or reduce mortality due to progressive heart failure. In fact, MADIT II results show that the incidence of new onset or worsening heart failure was somewhat higher in the ICD group versus the group of patients that received conventional therapy.

With these findings, it becomes apparent that physicians can optimize outcomes in left ventricular dysfunction and heart failure with combined use of CRT and ICD. In fact, new data at ACC provides further support for this argument. In the COMPANION trial, more than 1,600 patients received medical therapy alone, CRT, or CRT plus ICD. There was a highly significant 43% reduction in all-cause mortality in the group of patients that received both CRT and ICD. In contrast, there was a non-significant 24% reduction in all cause mortality in the group that received CRT only.