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.