Small and Large Left Ventricles Both Linked to Higher Mortality in HF

Both abnormally small and abnormally large left ventricles (LVs) are independently associated with higher mortality risk among patients hospitalized with heart failure (HF), challenging the field's traditional focus on ventricular dilation alone, according to a new nationwide cohort study published in JAMA Cardiology.¹

“A U-shaped association emerged between LV dimension and mortality; both abnormally small and large ventricles were independently associated with increased all-cause and cardiovascular mortality, with particularly strong associations observed in younger patients,” wrote the researchers of the study. “The presence of either an abnormal LV or systolic dysfunction, whether independently or in combination, was associated with an elevated mortality risk in patients with HF.”

The analysis drew on data from the Chinese Cardiovascular Association (CCA) Database–Heart Failure Center Registry, encompassing 273,921 patients hospitalized with HF across 723 centers in 31 provincial-level regions of China between January 2018 and May 2022. Patients were classified by left ventricular end-diastolic diameter (LVEDD) into small, normal, or large LV groups using American Society of Echocardiography criteria, then tracked for mortality through the national death registry through November 30, 2022.

A U-Shaped Mortality Curve

Among the cohort (median [IQR] age, 71 [62.0-79.0] years; 59% male), 4.8% had a small LV, 56.0% had a normal LV, and 39.3% had a large LV. Restricted cubic spline analysis revealed a significant U-shaped relationship between LVEDD and both all-cause and cardiovascular mortality (P for nonlinearity < .001), with sex-specific inflection points identified at 47 mm for men and 43 mm for women, beyond which mortality risk increased as LVEDD deviated in either direction.

After multivariable adjustment for 24 clinical covariates, a small LV was associated with a 32% increase in all-cause mortality risk (adjusted HR [aHR], 1.32; 95% CI, 1.28-1.37) and a large LV with a 38% increase (aHR, 1.38; 95% CI, 1.35-1.40), relative to a normal-sized ventricle. The gap widened for cardiovascular mortality, where a large LV carried a 54% higher risk (aHR, 1.54; 95% CI, 1.51-1.58) vs a 22% higher risk for a small LV.

More than 80% of patients with a small LV had preserved ejection fraction, suggesting impaired preload reserve may contribute more than systolic dysfunction, although alternative mechanisms such as concentric hypertrophy or cardiac amyloidosis may also play a role, according to the authors. Large LV was linked primarily to systolic dysfunction (85.7% had reduced ejection fraction). The authors also identified a distinct high-risk phenotype—isolated LV dilation with preserved ejection fraction, present in 5.6% of the cohort—that independently increased all-cause mortality risk by 26% despite an apparently normal EF.

Age Modifies but Does Not Eliminate Risk

Younger patients (aged 18 to 49 years) showed the steepest relative mortality increases associated with abnormal LV size, while patients 80 years and older had attenuated but still significant relative risks alongside much higher absolute mortality rates. Findings remained consistent across sensitivity analyses, including population-specific size thresholds, competing-risk models, and adjustment for ejection fraction and natriuretic peptide levels.

The results add to a growing body of evidence on HF's expanding footprint: an estimated 6.7 million American adults currently live with HF, and lifetime risk has climbed to 24%, underscoring the large population that may ultimately benefit from more granular structural risk stratification if these findings are prospectively validated.²

Managed Care Implications

The findings suggest that LVEDD—a routine, low-cost echocardiographic measurement already captured in most HF evaluations—could complement ejection fraction in identifying patients hospitalized with HF who may warrant closer monitoring or follow-up without requiring additional imaging.¹ The study also highlights that patients with preserved ejection fraction and isolated LV dilation may represent a higher-risk subgroup that could be overlooked by ejection fraction–focused risk models alone.

However, the authors emphasized that the identified LVEDD thresholds are hypothesis-generating and require prospective validation before informing clinical guidelines or formal risk-stratification protocols. Because the registry included only hospitalized patients in China, additional studies are needed to determine whether these findings generalize to outpatient populations and other racial and ethnic groups.

“This large-scale study established that a U-shaped association exists between LVEDD and mortality in HF, suggesting that both abnormally small and abnormally large ventricles signify high risk, likely through distinct mechanisms,” wrote the researchers. “These findings support the integration of LV size assessment into routine risk stratification to guide personalized management.”

References

1. Wang H, Zhang L, Ji C, et al. U-shaped association between left ventricular dimension and mortality in patients with heart failure. JAMA Cardiol. Published online August 5, 2026. doi:10.1001/jamacardio.2026.2779
2. Heart Failure Society of America. HF STATS 2025: heart failure epidemiology and outcomes statistics—an updated 2025 report from the Heart Failure Society of America. J Card Fail. 2026;32(2):439-498. doi:10.1016/j.cardfail.2025.07.007