Small heart size and premature death in 366,484 individuals with normal ejection fraction

Background
In patients with preserved left ventricular ejection fraction (LVEF), small ventricular size has been associated with reduced functional capacity, but its impact on clinical outcomes is unclear.

Objectives
The goal of this study was to determine the relationship between small heart size and premature mortality within a large multicenter adult patient cohort with transthoracic echocardiographic examinations.

Methods
We divided 366,484 individuals with LVEF ≥50% (including a subset of 279,442 individuals with high-normal LVEF ≥60%) by sex and increasing quartiles for LV end-diastolic volume (LVEDV), LVEDV indexed to body surface area (LVEDVi), and LV end-diastolic diameter to assess associations with 5-year mortality through linkage with the National Death Index.

Results
During approximately 2 million person-years of follow-up, 65,241 deaths occurred. Increasing LV chamber size was associated with reduced odds of 5-year all-cause mortality, particularly for higher LVEF. As compared with the larger quartiles, the smallest cardiac size quartiles were associated with higher 5-year all-cause mortality, even after adjusting for age. The smallest LVEDVi quartile was associated with a 14% to 18% higher odds of 5-year all-cause mortality, with a greater effect with high-normal LVEF. There was a U-shaped relationship between LV chamber size and all-cause mortality. For cardiovascular-related mortality, females in the smallest LVEDVi quartile had a 17% increased odds of mortality, which increased to 30% in those with LVEF ≥60%. In men, there was no significant association between smallest cardiac size and cardiovascular-related mortality.

Conclusions
In individuals with normal LVEF, small ventricular size is associated with increased mortality, particularly among females and those with higher LVEF.

© 2025 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).