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Atrial Fibrillation can adversely impact Heart Failure with Preserved Ejection Fraction by its association with Heart

Sanjeev Saksena^1,2, April Slee¹, Andrea Natale³

¹Electrophysiology Research Foundation, 161 Washington Valley Road, Suite 201, Warren, NJ 07059, USA.

Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology

|April 20, 2023

Insights

Prevalent atrial fibrillation (AF) is an independent risk factor for cardiovascular death and hospitalizations in heart failure with preserved ejection fraction (HFpEF). AF is associated with worsening heart failure and pump failure death, but not sudden death.

Area of Science:

Cardiology
Heart Failure Research
Atrial Fibrillation Studies

Background:

Prevalent atrial fibrillation (AF) is linked to increased cardiovascular (CV) death and hospitalizations in patients with heart failure with preserved ejection fraction (HFpEF).
The independent role of AF in adverse CV outcomes within the HFpEF population requires further elucidation.

Purpose of the Study:

To evaluate if prevalent AF independently contributes to excess CV death in HFpEF.
To investigate the impact of AF on cause-specific mortality and heart failure (HF) morbidity in HFpEF patients.

Main Methods:

Utilized propensity score-matched (PSM) cohorts from the TOPCAT Americas trial.
Compared subjects with any AF history or on ECG versus PSM controls without AF.
Analyzed cause-specific mortality and HF morbidity over a mean follow-up of 2.9 years.

Main Results:

Any AF was associated with increased CV hospitalizations (HR 1.33) and heart failure hospitalizations (HR 1.44).
AF on ECG increased the risk of CV death (HR 1.46) and pump failure death (PFD) (HR 2.21).
Both AF presentations were linked to PFD in advanced HFpEF (NYHA class III/IV).

Conclusions:

Prevalent AF is an independent risk factor for adverse CV outcomes in HFpEF, specifically worsening HF, HF hospitalizations, and PFD.
AF is not associated with an increased risk of sudden death in HFpEF.
AF contributes to HF progression in early symptomatic HFpEF and PFD in advanced HFpEF.

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Abstract

Aims:

Prevalent atrial fibrillation (AF) is associated with excess cardiovascular (CV) death (D) and hospitalizations (H) in heart failure (HF) with preserved ejection fraction (pEF). We evaluated if it had an independent role in excess CVD in HFpEF and studied its impact on cause-specific mortality and HF morbidity.

Methods And Results:

We used propensity score-matched (PSM) cohorts from the TOPCAT Americas trial to account for confounding by other co-morbidities. Two prevalent AF presentations at study entry were compared: (i) subjects with Any AF event by history or on electrocardiogram (ECG) with PSM subjects without an AF event and (ii) subjects in AF on ECG with PSM subjects in sinus rhythm. We analyzed cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years. A total of 584 subjects with Any AF event and 418 subjects in AF on ECG were matched. Any AF was associated with increased CVH [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.11-1.61, P = 0.003], HFH (HR 1.44, 95% CI 1.12-1.86, P = 0.004), pump failure death (PFD) (HR 1.95, 95% CI 1.05-3.62, P = 0.035), and HF progression from New York Heart Association (NYHA) classes I/II to III/IV (HR 1.30, 95% CI 1.04-1.62, P = 0.02). Atrial fibrillation on ECG was associated with increased risk of CVD (HR 1.46, 95% CI 1.02-2.09, P = 0.039), PFD (HR 2.21, 95% CI 1.11-4.40, P = 0.024), and CVH and HFH (HR 1.37, 95% CI 1.09-1.72, P = 0.006 and HR 1.65, 95% CI 1.22-2.23, P = 0.001, respectively). Atrial fibrillation was not associated with risk of sudden death. Both Any AF and AF on ECG cohorts were associated with PFD in NYHA class III/IV HF.

Conclusion:

Prevalent AF can be an independent risk factor for adverse CV outcomes by its selective association with worsening HF, HFH, and PFD in HFpEF. Prevalent AF was not associated with excess sudden death risk in HFpEF. Atrial fibrillation was also associated with HF progression in early symptomatic HFpEF and PFD in advanced HFpEF.

Trial Registration:

TOPCAT trial is registered at www.clinicaltrials.gov:identifier NCT00094302.

Keywords:

Antiarrhythmic therapy Arrhythmias Atrial fibrillation Cardiovascular mortality Clinical trials Heart failure with preserved ejection fraction Outcomes research Sudden death

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