Background
Left ventricular ejection fraction (LV-EF) is a central prognostic marker in heart failure (HF) and indicates eligibility for neurohumoral treatment strategies when reduced. However, evidence guiding therapeutic decisions in subjects with mildly reduced LV-EF (41–49%) remains limited, as most available data originate from subgroup analyses, and these subjects may exhibit structural characteristics typically seen in heart failure with preserved ejection fraction. This highlights an important limitation of relying solely on LV-EF for risk stratification and treatment guidance.
Aim
The objective of our study was to determine the prognostic value of MRI-derived indexed left ventricular end-diastolic volume (LVEDVi) beyond LV-EF in participants from the UK Biobank.
Methods and results
MRI-derived LVEDVi was available for N=5527 participants without the diagnosis of HF recruited between 2006 and 2010 in the United Kingdom. Participants without HF allowed us to investigate the additive value of LVEDVi beyond LV-EF in a cohort unconfounded by heart failure medication.
In participants with a LV-EF ≥50%, increased LVEDVi was not associated with adverse outcomes (Log rank p = 0.41). In contrast, among subjects with LV-EF < 50%, elevated LVEDVi was associated with a significantly higher incidence of 4-point major adverse cardiovascular events (4P-MACE, i.e. cardiovascular death, myocardial infarction, stroke and hospitalisation for heart failure; log-rank p < 0.0001) compared with subjects who had normal LVEDVi. To further assess the prognostic impact of LVEDVi beyond reduced LV-EF, subjects were stratified by LV-EF (41–49% or ≤40%) and LVEDVi (normal or increased). Notably, after full adjustment for cardiovascular history, biomarkers (hsCRP, HbA1c, LDL, eGFR), sex, age, and body mass index, individuals with increased LVEDVi and an LV-EF of 41–49% exhibited a 4P-MACE risk comparable to that of subjects with LV-EF ≤ 40% and increased LVEDVi (LV-EF 41–49%: HR 2.7 [95% CI 1.9–3.8]; LV-EF ≤ 40%: HR 2.46 [95% CI 1.9–3.2]). This heightened risk was predominantly driven by higher rates of myocardial infarction and hospitalization for heart failure. In addition, participants with increased LVEDVi and an LV-EF of 41–49% had significantly elevated plasma NT-proBNP concentrations compared with those with normal LVEDVi in the same LV-EF category (p = 0.03). Importantly, natriuretic peptide levels in these subjects were comparable to those observed in individuals with LV-EF ≤ 40%, irrespective of LVEDVi.
Conclusion
An increased LVEDVi independently predicts adverse outcomes in subjects with reduced LV-EF. Therefore, LVEDVi provides important prognostic value beyond ejection fraction and indicates subjects with increased natriuretic peptide levels suggesting increased neurohumoral activation.
