Incidence, predictors and associated outcomes of EF change in HF patients
Prevalence and Prognostic Implications of Longitudinal Ejection Fraction Change in Heart Failure
Introduction and methods
Heart failure (HF) phenotyping and therapy decisions are profoundly determined by assessment of ejection fraction (EF) . In addition, EF also independently provides prognostic information . Baseline EF assessment therefore is mandatory for purposes of diagnosis, prognostication, and treatment assignment in every HF patient [1,2]. However, EF may change over time [3-5], requiring renewed stratification and prognostic evaluation. Furthermore, worsening EF may indicate HF treatment, whereas benefits and risks of continuation vs. withdrawal of treatment with improving EF remain unknown. This indicates the need for comprehensive assessment of changes in EF in large HF populations. However, most contemporary studies only focus on recovery of EF [6-12], and do not examine the whole spectrum of EF changes across all EF categories, including determinants of change and associated prognosis.
This study (n=4.942) therefore examined the incidence and type of EF change, the predictors of different types of EF change (increase and decrease), and the prognostic implications of different types of EF change in the large contemporary and unselected SwedeHF (Swedisch Heart Failure) study population. HF patients with ≥2 consecutive EF assessment were enrolled between May 2000 and Dec 2012. Data of the SwedeHF were linked to data on mortality from the Population Registry, data on baseline comorbidities and hospitalization for HF (HHF) from the Patient Registry, and socio-economic data from the Statistics Sweden SCB. HF patients were categorized based on EF: HFrEF [EF <40%], HFmrEF [EF 40%-49%], and HFpEF [EF ≥50%]. EF decrease was defined as pooled transitions from HFpEF to HFmrEF, HFpEF to HFrEF, or HFmrEF to HFrEF. EF increase was defined as pooled transitions from HFrEF to HFmrEF, HFrEF to HFpEF, or HFmrEF to HFpEF. Stable EF was defined as no changes among EF groups. Primary outcome was a composite of all-cause mortality and HHF.
Incidence and EF change patterns
- Median time between EF examinations was 1.4 (IQR: 0.5-3.0) years and follow-up was >1 day.
- Of 4.942 HF patients at baseline, 18% had HFpEF, 19% had HFmrEF, and 63% had HFrEF.
- Overall, decreased EF was seen in 14% of patients, increased EF in 21%, and stable EF in 65%.
- During follow-up, 21% and 18% of HFpEF patients transitioned to HFmrEF and HFrEF, respectively; 37% and 25% of HFmrEF patients transitioned to HFrEF and HFpEF, respectively; and 16% and 10% of HFrEF patients transitioned to HFmrEF and HFpEF, respectively.
Predictors of EF change
- A wide range of variables independently predicted an increase in EF, including no use of ACEi/ARBs, female sex, indicators of less severe HF, and modifiable comorbidities (e.g. anemia and AF).
- A wide range of variables independently predicted a decrease in EF, including concomitant diabetes, ischemic heart disease, and more severe HF.
EF change and outcomes
- After adjustments, an increase in EF was linked to significantly reduced risk of the composite outcome (HR: 0.62, 95%CI: 0.55-0.69), compared to stable EF, whereas a decrease in EF was linked to an increased risk (HR: 1.15, 95%CI: 1.01-1.30).
- Using stable HFrEF as reference, improved outcomes were seen in patients who transitioned from HFrEF to HFmrEF (HR: 0.55, 95%CI: 0.47-0.64) or to HFpEF (HR: 0.42, 95%CI: 0.33-0.53) or to stable HFmrEF (HR: 0.73, 95%CI: 0.62-0.85), whereas outcomes were not improved with all other transitions.
- Downward transition from HFpEF to HFrEF was associated with increased risk of primary outcome (HR adj: 1.46, 95%CI: 1.15-1.85), whereas transition to HFpEF from HFrEF was associated with decreased risk of outcome (HR adj: 0.54, 95%CI: 0.41-0.73), compared with stable HFpEF.
- Both transitions from HFmrEF to HFpEF (HR adj: 1.32, 95%CI: 1.03-1.70) and to HFrEF (HR adj: 1.40, 95%CI: 1.13-1.75) were linked to higher risk of primary outcome, whereas transition to HFmrEF from HFrEF was associated with lower risk of outcome (HR adj: 0.76, 95%CI: 0.60-0.96), compared with stable HFmrEF.
- Transition to HFrEF from HFpEF (HR adj: 1.34, 95%CI: 1.09-1.15) was linked to higher risk of primary outcome, compared with stable HFrEF.
This nationwide HF cohort showed an increase in EF over time in one-fourth of patients with HFrEF and HFmrEF, and a decrease in EF in more than one-third of those with HFpEF and HFmrEF. A wide range of important clinical, treatment, and organizational factors predicted EF changes. Decrease in EF was linked to higher risk of all-cause mortality and HHF, particularly in those transitioning to HFrEF.