Rhythm control in atrial fibrillation--one setback after another.

Atrial fibrillation, the most common sustained arrhythmia observed in hospitalized patients, is associated with substantial morbidity, and its occurrence approximately doubles the rate of death as compared with that of patients in whom sinus rhythm is maintained. The global effect of atrial fibrillation on public health is so great that international professional organizations have integrated the results of seminal studies to progressively formulate data-driven management guidelines.1 Patients with heart failure are at increased risk for atrial fibrillation and constitute an important subgroup of all patients with this arrhythmia. Data from trials involving patients with atrial fibrillation have shown that a “rhythm-control strategy,” in which antiarrhythmic drugs are used along with serial electrical cardioversion when necessary, is not superior to a “rate-control strategy,” in which no specific efforts are made to maintain sinus rhythm and heart-rate control is the main objective.2,3 However, the same outcome may not hold true for the large subgroup of patients with heart failure. In this issue of the Journal, two groups of international investigators — Roy et al.4 and Køber et al.5 — describe the results of clinical trials that will contribute to the evolution of guidelines for the treatment of patients with heart failure and atrial fibrillation. The Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial (ClinicalTrials.gov number, NCT00597077)4 was a prospective, randomized, multicenter comparison of a rhythm-control strategy and a rate-control strategy. All 1376 patients in the study by Roy et al. had a left ventricular ejection fraction of 35% or less, heart-failure symptoms, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. Patients were followed for a mean of 37 months. Not only was there no significant difference in the rate of death from cardiovascular causes (27% in the rhythm-control group and 25% in the rate-control group, P = 0.59), but there was no significant difference in any of the secondary outcomes, including death from any cause and worsening heart failure. Nature has equipped the human heart with a complex electrical system for the purpose of coordinated propulsion of blood under a variety of physiologic conditions. Considerable effort is expended by the heart to maintain sinus rhythm. Cardiac electrophysiologists view atrial fibrillation as a system failure. They are likewise frustrated by the conundrum that atrial fibrillation is associated with increased morbidity and mortality, yet attempts to prove that a strategy to maintain nature’s rhythm has a favorable effect on patients have been met with one setback after another.2-4 Fortunately, the story does not end here. There are at least four concepts that help reconcile this paradox. First, the rhythm-control strategies used in the AF-CHF trial and the other cited studies do not guarantee the maintenance of sinus rhythm, and not all patients in the rate-control group had persistent atrial fibrillation. Similar to the findings in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial (ClinicalTrials.gov number, NCT00000556),2 the absolute difference in actual heart rhythm during follow-up in the AF-CHF trial was approximately 40%, since sinus rhythm was not maintained in 100% of the patients in the rhythm-control group and was maintained in some of the patients in the rate-control group. Some 58% of patients in the e d i t o r i a l