Interpreting Longitudinal LV Size Reduction: The Role of Age, Comorbidity, and Loading Conditions

Dear Editor,We read with great interest the study by Gotsman et al. examining 6,232 adults with normal baseline LV size, in which longitudinal decreases in LV end-diastolic diameter (LVEDD) were independently associated with higher mortality (multivariable HR 1.19, 95% CI 1.03–1.37), along with a U-shaped association indicating risk with both decreases and increases in LV size [1]. The design of including at least two echocardiograms 1 year apart, normal baseline LVEDD defined by guidelines, and standardized measurements provides valuable longitudinal insight into remodeling biology.Several points may further strengthen interpretation. First, multimorbidity and residual confounding deserve closer attention. The LVEDD increase group carried the heaviest burden of ischemic heart disease (51%), prior myocardial infarction (32%), heart failure (35%), chronic renal failure (31%), prior stroke (24%), and hemodialysis (8%), all strongly linked to mortality, yet the decrease group remained associated with mortality after adjustment. Models that explicitly quantify multimorbidity load, such as counts or indices, could help ensure the LVEDD-outcome signal is not partly reflecting unmeasured disease complexity.Second, age effects merit further sensitivity analysis. The decrease group was older (70 ± 15 years), and LVEDD fell progressively with increasing age, consistent with age-related concentric remodeling and diastolic impairment. Although age was included in multivariable models, residual confounding is likely. Propensity-score matching within age strata, or alternatively an analysis restricted to a narrow age range such as 65–75 years, could better isolate remodeling from chronological age.Third, loading conditions may have influenced chamber size. With 25 percent of patients having chronic renal failure and 5 percent on hemodialysis, day-to-day volume variation may bias LVEDD and LVEDV. Practical sensitivity analyses using inferior vena cava diameter or collapsibility, which is often recorded in echocardiography reports, and examining the timing of echocardiography relative to dialysis sessions would be very informative.Fourth, in terms of myocardial mechanics, the authors comprehensively reported conventional indices and assessed RV function using fractional area change, TAPSE, and tissue Doppler S′. If available, the incorporation of serial global longitudinal strain (GLS) measurements could clarify whether adverse outcomes in the decrease group are mediated by subtle longitudinal systolic dysfunction despite preserved EF. If GLS data are not available, this represents a valuable future direction.We also note the robustness checks already provided. Restricted cubic splines confirmed the U-shaped risk pattern, and annualized change greater than 1 mm per year was associated with higher hazards for both decreases and increases. Supplementary analyses of LV volumes, where both increases and decreases greater than 30 cm3 were linked to adverse outcomes, reinforce that deviation from stability in either direction portends harm.In summary, Gotsman et al. present compelling evidence that longitudinal LV size change carries prognostic meaning in hearts starting with normal size. The manuscript could be further strengthened by explicit multimorbidity modeling, age-matched or age-restricted analyses, practical sensitivity analyses using inferior vena cava indices and dialysis timing, and, if available, serial GLS. These steps would help distinguish remodeling related to age and comorbidity from an independently adverse phenotype of progressive LV shrinkage, refining both risk stratification and clinical interpretation.The authors have no conflicts of interest to declare.The authors have not received any financial support.M.G.: drafting and final approval. A.H.: conceptualization, drafting, and literature review, Y.H.: conceptualization, literature review, drafting, and final approval.