Viral respiratory tract infections in heart failure with mildly reduced and preserved ejection fraction: a secondary analysis of the FINEARTS-HF trial

Background

Viral respiratory tract infections (VRTIs) may worsen outcomes in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and are potentially preventable. We explored the frequency and implications of VRTIs in patients with HFmrEF/HFpEF treated in a contemporary clinical trial.

Purpose

We evaluated clinical prognosis and time-course of risk following a VRTI in patients with HFmrEF/HFpEF included in the FINEARTS-HF (Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction) trial.

Methods

The FINEARTS-HF study was a global, double-blind trial randomizing 6,001 patients with HF and left ventricular ejection fraction (LVEF) of ≥40 % to finerenone or placebo. The primary outcome was a composite of total HF events and cardiovascular (CV) death. Prognosis after first occurrences of investigator-reported COVID-19, influenza, respiratory syncytial virus (RSV), and unspecified VRTI were examined using time-updated Cox proportional hazard models.

Results

A first VRTI occurred in 1,079 (18%) of FINEARTS-HF participants during follow-up of 2.7 years; most (80%) of reported VRTI were COVID-19 infections. Patients who experienced a VRTI were slightly older, more often female, and had slightly lower eGFR, but did not differ in terms of cardio-kidney metabolic comorbidities, left ventricular ejection fraction, or natriuretic peptide levels compared with patients without VRTI. A first VRTI was associated with increased subsequent risk of a first HF event or CV death (adjusted hazard ratio [aHR] 1.25, 95% CI 1.04-1.49), HF event (aHR 1.29, 95% CI 1.05-1.59), non-CV death (aHR 3.59, 95 % CI 2.84-4.54), and all-cause death (aHR 1.80, 95% CI 1.53-2.12); all P-values<0.02, but not CV death alone (Figure). The excess risk persisted for 3 months after the VRTI and was most pronounced for non-CV death, where incidence rates per 100 patient-yrs were 61.4 within 1 month (aHR 30.2, 95 % CI 22.4-40.8), 9.1 during months 1-3 (aHR 4.15, 95 % CI 2.46-7.00), and 3.2 after 3 months (aHR 1.52, 95 % CI 1.09-2.13); all P-values<0.02. Risk estimates were virtually unchanged when excluding patients in whom the VRTI coincided with a HF event (n = 11). Finerenone treatment did not alter the incidence of first VRTI compared with placebo (HR 1.03, 95 % CI 0.91-1.16, P=0.66). Randomized therapy had to be interrupted or withdrawn in a minority of participants after VRTI (6%) and treatment benefits of finerenone on the primary clinical outcome did not appear attenuated after VRTI (P-interaction=0.10).

Conclusions

In a contemporary cohort of patients with HFmrEF/HFpEF, VRTI was associated with markedly higher risks of clinical events, particularly in the months following infection. Ongoing strategies are needed to limit VRTI transmission in high-risk patients with HF.

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