HFmrEF resembles HFrEF rather than HFpEF regarding IHD
Significance of Ischemic Heart Disease in Patients With Heart Failure and Preserved, Midrange, and Reduced Ejection Fraction: A Nationwide Cohort Study
In recent international heart failure (HF) guidelines, patients with an ejection fraction (EF) of 40% to 49% were characterized as having HF with midrange EF (HFmrEF) [1,2]. Ischemic heart disease (IHD) is associated with an increased risk of HF. Although there is evidence pointing to an increased favor of HFmrEF and HF with preserved EF (HFpEF) post-IHD events compared to HF with reduced EF (HFrEF), there are crucial gaps in evidence, including the understanding of how different HF types affect ischemic outcomes and the uncertainty about the role of established IHD in determining the risk of new ischemic events or other outcomes and the role of established IHD in longitudinal changes in EF in HFmrEF and HFpEF and HFrEF [3-5].
In the Swedish Heart Failure Registry, any patient with HF was registered according to clinical judgement. In this analysis, associations between prevalent IHD and risk of new ischemic and other events in patients with different types of HF were evaluated as well as between concurrent prevalent and incident IHD and longitudinal EF changes across the different HF types. For this, 42 987 patients were evaluated during a median follow-up of 2.2 years. The primary outcome was time to a fatal or non-fatal IHD event and the secondary outcomes were time to fatal or non-fatal HF event, fatal or non-fatal cardiovascular (CV) event and all-cause mortality.
- 23.2% of patients had HFpEF, 21.4% had HFmrEF and 55.4% had HFrEF. The prevalence of IHD in these subgroups was 52.4%, 60.7% and 60.0% respectively.
- HFpEF was associated with a lower prevalence of IHD compared with both HFmrEF (adjusted RR: 0.91; 95% CI: 0.89–0.93) and HFrEF (RR: 0.90; 95% CI: 0.88–0.92), whereas no difference was observed between HFmrEF and HFrEF (RR: 1.00; 95% CI: 0.98–1.01).
- During a median follow-up of 2.2 years, there were 9629 new non-fatal or fatal IHD events, 16 005 non-fatal or fatal HF events, 26 734 non-fatal or fatal CV events and 16 866 all-cause death events.
- After full adjustment, risk of new IHD events was lower in HFpEF compared with both HFmrEF (HR: 0.89; 95% CI: 0.84–0.95) and HFrEF (HR: 0.84; 95% CI: 0.80–0.90), but only marginally lower in HFmrEF versus HFrEF (HR: 0.95; 95% CI: 0.90–1.00).
- In all 3 HF categories, prevalent IHD was independently associated with increased risk of all 4 primary/secondary outcomes, except for all-cause mortality in HFpEF.
- Strongest associations were observed for new IHD events, for which the risk was >3-fold increased among HFrEF patients with IHD versus no IHD at baseline and more than doubled among HFmrEF and HFpEF patients with IHD versus no IHD at baseline.
- Risk of HF associated with baseline IHD was slightly and similarly increased within all HF categories, whereas increases in risk for CV events and all-cause mortality seemed somewhat greater in HFrEF than in HFmrEF and HFpEF.
- More than one third of HFpEF and HFmrEF patients experienced worsening EF during follow-up, whereas approximately one fourth of HFmrEF and HFrEF patients improved their EF.
- Patients with IHD in general, and new IHD events in particular, were more likely to experience worsening EF and less likely to experience improvement in EF over time.
In the Swedish Heart Failure Registry, HFmrEF resembled HFrEF rather than HFpEF, with respect to IHD as underlying cause and HFmrEF and HFrEF had an elevated risk of ischemic events compared with HFpEF. Established IHD had an adverse impact on most of study outcomes in all HF categories, although most prominent for new IHD events and in HFrEF. These findings are of importance to future research strategies on prevention and treatment of different HF types and IHD.