Supplementary Material for: Longitudinal Decrease in Left Ventricular Size with Age: Impact on Mortality and Cardiovascular Hospitalization

Background: A small left ventricular (LV) chamber size may reflect adverse cardiac remodeling and have prognostic implications. The prognostic significance of reductions in LV size in hearts with normal baseline LV size remains unclear. This study investigated clinical characteristics and outcomes associated with longitudinal decreases in LV size in this population.
Methods: We analyzed echocardiographic data from 6,232 adults with normal baseline left ventricular end-diastolic diameter (LVEDD), with a mean interval of 4.8 years between baseline and follow-up echocardiograms. Participants were categorized by LVEDD change from baseline: No Change (<5 mm), Decreased (≥5 mm), and Increased (≥5 mm).
Results: A decrease in LVEDD was observed in 24% of participants (mean change -9±3 mm) and was significantly associated with older age, female sex, decreased volumes, concentric remodeling and diastolic dysfunction. LVEDD increase (13%, 9±4 mm) was associated with higher prevalence of cardiovascular comorbidities and reduced LVEF. Multivariable Cox regression showed decreased LVEDD was independently associated with increased mortality (HR 1.19, 95% CI 1.03-1.37, p=0.02). Sensitivity analysis using annual LVEDD change (>1mm/year) demonstrated a significant association with mortality (HR 1.45, 95% CI 1.26-1.66, p<0.001) and the combined endpoint of death/cardiovascular hospitalization (HR 1.26, 95% CI 1.12-1.41, p<0.001). Restricted cubic spline analysis confirmed a U-shaped relationship between continuous LVEDD change and mortality. Furthermore, increase or decrease in left ventricular end-diastolic volumes were associated with increased mortality and death/cardiovascular hospitalization.
Conclusions: A progressive decrease in LVEDD in normal-sized hearts was independently associated with adverse outcomes, highlighting the prognostic importance of declining LV size.