Low-normal left ventricular ejection fraction identifies early structural remodeling in cardio-oncology patients

Background

Left ventricular ejection fraction (LVEF) ≥50% is commonly considered preserved; however, values in the low-normal range may reflect early myocardial vulnerability. In cardio-oncology patients, reliance on LVEF alone may underestimate subclinical structural impairment.

Purpose

To compare baseline echocardiographic characteristics and cardiovascular outcomes between cardio-oncology patients with normal (LVEF ≥55%) versus low-normal LVEF (LVEF 50–54%).

Methods

A single-centre observational cohort study including cardio-oncology patients with baseline LVEF ≥50% assessed prior to or at the initiation of cancer therapy. Baseline clinical characteristics and echocardiographic parameters were compared. The primary outcome was a composite cardiovascular endpoint (MACE), defined as cardiovascular death, hospitalization for heart failure, clinically significant arrhythmia or new left ventricular systolic dysfunction.

Results

A total of 105 patients were included; 92 (87.6%) had normal LVEF and 13 (12.4%) low-normal LVEF. Mean age was 65.5 ± 12.2 years in the normal LVEF group and 68.1 ± 9.2 years in the low-normal LVEF group (p = 0.478), with a male predominance in both groups (56.5% vs. 69.2%, p = 0.385). The prevalence of cardiovascular risk factors was similar, including hypertension (65.2% vs. 76.9%, p = 0.537), diabetes mellitus (30.4% vs. 46.2%, p = 0.343), dyslipidemia (63.0% vs. 61.5%, p = 0.916) and chronic kidney disease (9.8% vs. 15.4%, p = 0.624). Metastatic disease was present in 43.5% and 38.5%, respectively (p = 0.732). Exposure to potentially cardiotoxic therapies was common in both groups.

Indexed left ventricular end-diastolic volumes were comparable (51.5 ± 19.6 vs. 54.0 ± 27.8 mL/m², p = 0.746), as were indexed left atrial volumes (33.2 ± 15.5 vs. 34.1 ± 9.2 mL/m², p = 0.873). In contrast, patients with low-normal LVEF had significantly higher indexed left ventricular end-systolic volumes (34.5 ± 19.7 vs. 22.3 ± 13.5 mL/m², p = 0.025). Over a median follow-up of 23 months (IQR 0–94), MACE occurred in 6 patients (46.2%) with low-normal LVEF and in 39 patients (42.9%) with normal LVEF (p = 0.822). Other cardiovascular outcomes were similar between groups, including cardiotoxicity rates (35.9% vs. 38.5%, p = 0.856).

Conclusion

In cardio-oncology patients with preserved LVEF, a low-normal ejection fraction is associated with increased indexed LV end-systolic volumes, reflecting early structural systolic remodeling despite similar cardiovascular outcomes. These findings highlight the limitations of LVEF alone for cardiovascular risk stratification in cardio-oncology.