By Cara Pellegrini, MD

Assistant Professor of Medicine, University of California, San Francisco; Cardiology Division, Electrophysiology Section, San Francisco VA Medical Center

Dr. Pellegrini reports no financial relationships relevant to this field of study.

SYNOPSIS: Patients presenting with atrial fibrillation are at elevated risk for the development of heart failure, typically with preserved ejection fraction, which is associated with increased risk of death and hospitalization.

SOURCE: Pandey A, Kim S, Moore C, et al. Predictors and prognostic implications of incident heart failure in patients with prevalent atrial fibrillation. JACC Heart Fail 2017;5:44-52.

Atrial fibrillation (AF) and heart failure (HF) frequently coexist because of shared risk factors and pathophysiological mechanisms. Causality is likely bidirectional and complex. Their concurrence is associated with poor outcomes. Yet, there has not been the same focus of attention on risk stratification and prevention of HF in AF patients, as for other outcomes, such as stroke.

An important step toward that goal is the development of a greater understanding of what AF population subset is at the highest risk of developing HF. Pandey et al used a national, community-based registry of outpatients with AF (ORBIT-AF) to examine predictors and outcomes of incident HF. In addition to the primary outcome of HF incidence, they examined all-cause death, all-cause hospitalization, stroke/thromboembolism, and bleeding events. They collected demographic and medical history data, as well as insurance status, treatment strategy, and quality-of-life information. Patients presenting with prevalent HF at time of enrollment were excluded, although not patients with asymptomatic systolic or diastolic dysfunction or moderate-to-severe left ventricular hypertrophy (subclinical stage B HF); these patients were excluded in a sensitivity analysis.

The study population was largely elderly (> 70 years of age) and white, nearly half female, and mostly hypertensive with normal left ventricular ejection fraction. Of the 6,545 participants, 236 (3.6%) developed HF over a two-year follow-up period, for a rate of 1.58 per 100 person-years, markedly higher than that reported in the general population (0.2-1 per 100 person-years).

Although 64% of those who developed HF had a preserved ejection fraction (HFpEF), only 13.5% exhibited a documented drop in their ejection fraction (HFrEF); and 22.5% could not be classified due to missing ejection fraction information. Not surprisingly, older age, history of coronary artery disease, renal dysfunction, and significant valvular disease were independent predictors of HF incidence. Additionally, permanent AF, AF that is sustained and accepted by physician and patient (more end-stage AF), was associated with a 60% higher risk of HF than paroxysmal AF, and there was a 7% increased incidence of HF for each beat/minute increase in baseline heart rate.

Those who developed HF experienced significantly higher rates of all-cause death, all-cause hospitalization, and hospitalization for bleeding specifically. The authors concluded that incident HF in AF is relatively common, more likely HFpEF, predicted by AF-specific clinical characteristics, as well as traditional HF risk factors, and associated with poor long-term outcomes.

COMMENTARY

Particularly in the absence of a reduction in ejection fraction, it can be difficult to discern the true onset of heart failure in patients presenting with concomitant AF. AF alone can cause exercise limitation, left atrial enlargement, and elevation of biomarkers, such as NT-proBNP. Given the admitted inclusion of patients with subclinical stage B HF and the one-third to one-half of patients receiving diuretics at baseline, this study may have been identifying those in whom AF aided progression from subclinical to overtly clinical HF more than truly de novo HF cases. Nonetheless, the identification of a vulnerable subset of patients within the larger AF cohort is of value, as the number of people affected by these extremely prevalent conditions continues to increase.

The effect of insufficient ventricular rate control on the development of heart failure in AF patients has been debated. Although the RACE-2 (The Rate Control Efficacy in Permanent Atrial Fibrillation: a Comparison between Lenient versus Strict Rate Control II) trial did not demonstrate an increase in HF incidence in the lenient rate-control arm, there has been ongoing criticism that the study was underpowered and did not allow a long enough follow-up period to detect a potential difference.

The current registry-based study cannot ascribe causality, but does raise concerns that in the described setting — elderly patients demonstrating renal dysfunction, coronary artery disease, and more advanced AF — perhaps more stringent rate control should be considered.

There is a growing movement in AF management to treat AF earlier in the disease course and more aggressively. This appears to be truer in the HF population, as we have previously discussed, who appear to have all the more to gain with a rhythm control, and, specifically, an ablation-based strategy. In the current study, antiarrhythmic drug use was similar between the two groups, but there was a trend toward more catheter ablation in the group without incident HF.

Additional work is needed to determine the effect of risk factor modification, including AF ablation, on HF development, but this study adds to the mounting evidence supporting the idea that halting the process of AF-induced electrical and mechanical atrial remodeling may lead to beneficial effects for mitigating the stressors that cause HF.