Specific phenotypes impact heart failure (HF) outcomes in atrial fibrillation (AF) with hf with preserved ejection fraction (pEF): can there be a role for "complementary" therapy?

Introduction

Several phenotypes are associated with HFpEF. These include atrial fibrillation (AF), cardiovascular (CV) and non-CV comorbidities. AF is progressive disease and an independent risk factor for adverse HF outcomes but the independent impact of other comorbidities on AF or HFpEF or their progression is unclear.

Methods

We analyzed HFpEF subjects from the TOPCAT Americas trial for common comorbidities: Diabetes (D), hypertension (HTN), Obesity (O), ischemic heart disease (IHD) chronic pulmonary disease (COPD), asthma (A), hypothyroidism (THY) and dyslipidemia (DLD). We examined the independent impact of these comorbidities in 2 propensity score–matched (PSM) AF-HFpEF subgroups; (i) 548 subjects with Any AF event by history or on ECG with PSM subjects without any AF event and (ii) 418 subjects with AF on ECG PSM with subjects in sinus rhythm. We analyzed the composite TOPCAT primary outcome, cause-specific modes of death and HF morbidity during a mean follow-up period of 2.9 years.

Results

IHD independently increased risk for HFH (p= 0.048) and CVH (p=0. 001) in Any AF and in AF on ECG (HFH p<0.001; CVH p<0.001) as well as TOPCAT primary outcome (p=0.008). Among non-CV phenotypes, D independently increased risk in HFpEF subjects with Any AF for worsening HF (Hazard ratio {HR} 1.51, 95% confidence intervals (CI:) 1.16-1.98, p=0.0003), HF and CV hospitalization (H) {p=<0.001 & p=0.001 respectively), and TOPCAT primary outcome {p=0.002}. Similar findings were seen in AF on ECG subgroup with additional risk for sudden death (SD) {p=0.005}. COPD increased HFH (p<.001) and THY increased pump failure death (P=0.02). In contrast, no consistent impact of O, HTN or A could be identified.

Conclusion

1. There was a selective and independent adverse impact of D, COPD, THY and IHD on HF and CV outcomes in subjects with HFpEF, irrespective of AF status or presentation. These data support concomitant evaluation of aggressive upstream "complementary" therapy of comorbidities with rhythm control to improve HF and other outcomes in AF with HFpEF.

2. Enrolling subjects with D, THY, COPD and IHD in HFpEF clinical trials can increase HF event rates but their long-term impact on attrition of benefits of rhythm control interventions for AF, HFpEF or both should be considered.