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. 2022 Mar 22:9:787869.
doi: 10.3389/fcvm.2022.787869. eCollection 2022.

Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry)

Shinjeong Song  1 , Jum-Suk Ko  2 , Hye Ah Lee  3 , Eue-Keun Choi  4 , Myung-Jin Cha  4 , Tae-Hoon Kim  5 , Jin-Kyu Park  6 , Jung-Myung Lee  7 , Ki-Woon Kang  8 , Jaemin Shim  9 , Jae-Sun Uhm  5 , Jun Kim  10 , Changsoo Kim  11 , Jin-Bae Kim  7 , Hyung Wook Park  12 , Boyoung Joung  5 , Junbeom Park  1
Affiliations

Clinical Implications of Heart Rate Control in Heart Failure With Atrial Fibrillation: Multi-Center Prospective Observation Registry (CODE-AF Registry)

Shinjeong Song et al. Front Cardiovasc Med. .

Abstract

Background: Atrial fibrillation (AF) is treated by heart rate (HR) control. However, the optimal HR target in AF patients with heart failure (HF) remains unclear. To evaluate the clinical implication of the resting HR in AF patients with HF accompanied by preserved, mid-range, or reduced ejection fraction (HFpEF, HFmrEF, or HFrEF, respectively).

Methods: Echocardiographic data from June 2016 to April 2020 in a prospective, multicenter, observational registry from 11,104 patients were analyzed. The follow-up duration was 2.2 years. The main outcome was composite of death and hospitalization. We categorized patients according to the HF type and resting HR: ≤ 60 bpm, 61-80 bpm, 81-110 bpm, and >110 bpm.

Results: A total of 1,421 patients were enrolled in the study: 582 in the HFpEF group, 506 in the HFmrEF group, and 333 in the HFrEF group. The patients had a mean age of 69 ± 11 years and consisted of 872 (61.4%) men. Primary endpoint rates among HFpEF patients with 60 < HR ≤ 110 bpm were lower than those with HR ≤ 60 bpm (61-80 bpm group: hazard ratio, 0.66; 95% CI, 0.46-0.94; p = 0.021; 81-110 bpm group: hazard ratio, 0.60; 95% CI, 0.40-0.90; p = 0.013). Especially, HFpEF patients with HR 81-110 bpm had a lower incidence of hospitalization caused by HF aggravation than those with other HR strata (HR ≤ 80bpm strata or HR >110 bpm strata). In HFmrEF and HFrEF patients, the survival rates did not differ significantly among patients in the three groups with HR ≤ 110 bpm. Moreover, the event rates increased significantly in HFmrEF patients with HR >110 bpm (hazard ratio, 1.91; 95% CI, 1.16-3.14, p = 0.011).

Conclusion: In patients with AF and HFpEF, the resting HR has U-shaped associations with the overall primary endpoint. A lower or higher resting HR is associated with increased cardiovascular outcomes, especially in patients with HFpEF and AF.

Keywords: U shape curve; atrial fibrillation; heart failure; heart failure preserved ejection fraction; rate control.

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Conflict of interest statement

BJ has served as a speaker for Bayer, BMS/Pfizer, Medtronic, and Daiichi-Sankyo and has received research funds from Medtronic and Abbott. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Flowchart of the study population enrollment. CODE-AF, COmparison study of Drugs for symptom control and complication prEvention of Atrial Fibrillation.
Figure 2
Figure 2
Heart rate distribution in HFpEF, HFmrEF and HFrEF. HFpEF, heart failure with preserved ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFrEF, heart failure with reduced ejection fraction.
Figure 3
Figure 3
Kaplan–Meier curves. The primary endpoint according to the heart rate in patients with HFpEF, HFmrEF, and HFrEF is shown. HFpEF, heart failure with preserved ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFrEF, heart failure with reduced ejection fraction.
Figure 4
Figure 4
Cox regression analysis – penalized spline. The primary endpoint according to heart failure in patients with HFpEF, HFmrEF, and HFrEF is shown. (A) Penalized spline regression in HFpEF, (B) Penalized spline regression in HFmrEF, and (C) Penalized spline regression in HFrEF. HFpEF, heart failure with preserved ejection fraction; HFmrEF, heart failure with mid-range ejection fraction; HFrEF, heart failure with reduced ejection fraction.
Figure 5
Figure 5
Cox regression analysis—penalized spline. The primary endpoint according to heart failure in patients with HFpEF (reference heart rate of 88 bpm) is shown. HFpEF, heart failure with preserved ejection fraction.
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