Risk of major adverse cardiovascular events after RSV-related hospitalization among US adults with heart failure

Background/Introduction Although previous research has suggested an increased risk of cardiovascular events among adults with severe respiratory syncytial virus (RSV) disease,1 additional evaluations using large, representative data sources are needed to further understand this potential link. Purpose This study assessed risk of major adverse cardiovascular events (MACE) following RSV-related hospitalization among adults with pre-existing heart failure (HF) in the United States. Methods A retrospective cohort study was conducted using administrative claims from Optum’s de-identified Market Clarity Data (Oct 2015–Dec 2024). The study included adults aged ≥18 years with an RSV acute respiratory illness (ARI) involving hospitalization, based on ICD-10-CM diagnosis codes (index date: RSV-ARI start date). The RSV-ARI cohort was matched 1:5 with a comparator cohort without a recent ARI (no-ARI; matched on index date, age, and sex). Baseline characteristics were assessed in the 12 months pre-index; this analysis focused on adults who had pre-existing HF with reduced or preserved ejection fraction (HFrEF or HFpEF, respectively, as measured by ICD-10-CM diagnosis codes for systolic and diastolic HF). Patients were censored at continuous enrollment end, data availability end, receipt of RSV vaccination, or death. Hospitalization for HF (HHF) was analyzed as a time-to-recurrent-event outcome, with multivariable-adjusted Andersen-Gill Cox proportional hazards models comparing outcomes between cohorts. Additional cardiovascular outcomes were analyzed as time-to-first-event outcomes. Sensitivity analyses used entropy-balanced weighting to weight the no-ARI cohort to match baseline characteristics of the RSV-ARI cohort. Results The study included 24,414 adults with RSV-ARI and 122,070 matched adults (no-ARI cohort). Subgroups with pre-existing HFrEF or HFpEF included 1,169 and 3,048 RSV-ARI patients, respectively (1,939 and 3,805 in the respective no-ARI cohorts). HHF mean cumulative counts were consistently higher in the RSV-ARI versus no-ARI cohorts over the entire follow-up period. At 1 month post-index, the RSV-ARI cohorts with HFrEF or HFpEF had a mean of 0.467 (95% confidence interval: 0.431–0.503) and 0.397 (0.378–0.417) HHF, respectively (versus 0.024 [0.015–0.033] and 0.016 [0.012–0.021] respectively for the no-ARI cohorts). After adjusting for baseline differences, adults with pre-existing HF who experienced severe RSV disease had an increased risk of HHF. Adjusted hazard ratios of HHF for the RSV-ARI versus no-ARI cohorts were 2.96 (2.70–3.26) for adults with HFrEF and 3.03 (2.83–3.25) for adults with HFpEF. Table 1 presents risk of other adverse cardiovascular outcomes. Findings were consistent in sensitivity analyses. Conclusions These results add to the existing literature suggesting an association between severe RSV disease and increased risk of HHF and other cardiovascular outcomes among adults with pre-existing HFrEF or HFpEF.