Association Between Size of Left Ventricle and Long-Term Cardiovascular Events

Abstract

Background: The prognostic significance of small left ventricle (LV) in the general population and its association with cardiovascular disease remain elusive.

Methods: Using data from the UK Biobank, 39 363 participants underwent baseline cardiovascular magnetic resonance imaging and were categorized into 3 groups based on left ventricular end-diastolic volume index: small, normal, and large LV. Cox proportional hazards models were applied to evaluate the association between LV size and composite cardiovascular outcomes.

Results: An elevated prevalence of small LV was observed among the 4305 participants, with a notable trend toward increased occurrence in older individuals. Over a median follow-up of 5.21 years, 1500 cases of major adverse cardiovascular events, 1096 coronary heart disease, 288 ischemic stroke, and 722 deaths from any cause occurred. After adjusting for multiple confounders, hazard ratios (HRs) of small LV comparing the normal LV were 1.24 (95% CI, 1.07-1.44) for major adverse cardiovascular events, 1.29 (95% CI, 1.09-1.53) for coronary heart disease, 1.53 (95% CI, 1.11-2.09) for ischemic stroke, and 1.33 (95% CI, 1.08-1.64) for death from all causes. Notably, a U-shaped relationship was identified between left ventricular end-diastolic volume index and cardiovascular outcomes. Subgroup analysis revealed that, compared with women, the presence of a small LV in men exhibited a significant correlation with adverse cardiovascular events, thereby demonstrating potential value in disease prediction and risk stratification.

Conclusions: These findings highlight the importance of considering small LV as a prognostic marker for cardiovascular disease and underscore the need for further research to elucidate the underlying mechanisms and develop targeted interventions.

Keywords: cardiac magnetic resonance imaging; cardiovascular disease; left ventricular end‐diastolic volume index; small left ventricle.

Figure 1. Associations between LV size and MACE.

The cumulative incidence of MACE in subjects stratified by LV size (A) and adjusted associations of measures of left ventricular EDVi and MACE (B). The solid lines represent the adjusted HRs of left ventricular EDVi across the whole range and the dotted lines represent the corresponding 95% CIs. EDVi indicates end‐diastolic volume index; HR, hazard ratio; LV, left ventricle; and MACE, major adverse cardiovascular events.

Figure 2. Kaplan–Meier curves for cardiovascular outcomes stratified by LV size.

The cumulative incidence of coronary heart disease (A), heart failure (B), ischemic stroke (C), and death from any cause (D) in subjects stratified by LV size. Unadjusted Kaplan–Meier curves for cardiovascular outcomes stratified by LV size. LV indicates left ventricle; and MACE, major adverse cardiovascular events.

Figure 3. Adjusted association of left ventricular EDVi and cardiovascular outcomes.

Adjusted associations of measures of left ventricular EDVi and coronary heart disease (A) heart failure (B) ischemic stroke (C) and death from any cause (D). The solid lines represent the adjusted HRs of left ventricular EDVi across the whole range and the dotted lines represent the corresponding 95% CIs. CHD indicates coronary heart disease; EDVI, end‐diastolic volume index; and HR, hazard ratio.

Figure 4. Associations between LV size and MACE in subgroups.

Model adjusted for age, sex, race education, drinking status, smoking status, history of hypertension, diabetes, atrial fibrillation, Townsend deprivation index, physical activity, systolic blood pressure, diastolic blood pressure, body mass index, total cholesterol, hemoglobin concentration, white blood cell count, albumin, hemoglobin A1c, C‐reactive protein, use of cardiovascular medications, and left ventricular EF. EF indicates ejection fraction; HR, hazard ratio; LV, left ventricle; and MACE, major adverse cardiovascular events.

Figure 5. Adjusted associations of measures of left ventricular EDVi and MACE in subgroups.

The reference values (HR: 1) were set at the median value of each subgroup. The solid lines represented the adjusted HRs of left ventricular EDVi across the whole range and the shaded areas represented the corresponding 95% CIs. A, Age >65 years vs ≤65. U‐shaped relationship between left ventricular EDVi and MACE risk in both age subgroups (P for interaction=0.73). B, Men vs women. Elevated risk at left ventricular EDVi extremes in men, with attenuated association in women (P for interaction=0.03). C, Hypertension vs no hypertension. Persistent U‐shaped risk pattern across hypertension status subgroups (P for interaction=0.12). D, Diabetes vs no diabetes. U‐shaped relationship between left ventricular EDVi and MACE risk in participants with or without diabetes (P for interaction=0.55). E, Current drinking vs no current drinking. Robust U‐shaped relationship in drinkers and nondrinkers (P for interaction=0.45). F, Current smoking vs no current smoking. Risk pattern maintained in smokers and nonsmokers (P for interaction=0.83). G, BMI ≥25 vs <25 kg/m². Association independent of BMI stratification (P for interaction=0.85). H, Left ventricular EF ≥50% vs <50%. U‐shaped risk observed regardless of left ventricular EF thresholds (P for interaction=0.22). BMI indicates body mass index; EDVi, end‐diastolic volume index; EF, ejection fraction; HR, hazard ratio; LV, left ventricle; and MACE, major adverse cardiovascular events.