PEP/ET Ratio as a novel marker of subclinical heart failure and long term cardiovascular risk

Background

When cardiac function declines, the pre-ejection period (PEP) typically becomes prolonged and the ejection time (ET) becomes shortened, resulting in an increased PEP/ET ratio, which is associated with reduced left ventricular systolic function. Brachial PEP and ET can be automatically measured using an ankle–brachial index form device, and PEP/ET has recently been reported as a novel and useful marker of systolic and overall cardiac function. However, no large-scale studies have clarified the associations between PEP/ET, clinical outcomes, and cardiac function.

Purpose

The aim of this study was to investigate the relationship of PEP/ET with cardiovascular outcomes and cardiac function in patients with cardiovascular risk factors.

Methods

We analyzed 4,665 participants (mean age 69 ± 11 years; 52% male) enrolled in a coupling study that included individuals with at least one cardiovascular risk factor. PEP/ET was measured using the Vasera-1500 or 3000 system (Fukuda Denshi Co., Ltd.). Based on previous reports, a cutoff value of 0.425 was used to classify participants into two groups. The study endpoints were a composite endpoint (stroke, coronary heart disease and sudden death, heart failure, and aortic dissection) and hospitalization for heart failure. Analyses were also stratified by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (<300 pg/mL or ≥300 pg/mL). Left ventricular ejection fraction (LVEF) was assessed by transthoracic echocardiography in 415 participants for additional analysis.

Results

During a median follow-up of 5.0 years (20,053 person-years), 223 composite endpoints and 65 heart failure hospitalizations occurred. The high-PEP/ET group (N=408) had significantly more composite endpoints (hazard ratio [HR] 2.33, 95% confidence interval [CI] 1.66–3.28, p<0.001) and heart failure hospitalizations (HR 3.94, 95% CI 2.28–6.83, p<0.001) compared with the low-PEP/ET group (N=4,257), even after adjustment for covariates. LVEF was significantly lower in the high-PEP/ET group than in the low-PEP/ET group (57.0 ± 12.1 vs. 66.3 ± 9.6%, p<0.001).

In the NT-proBNP <300 pg/mL group, the high-PEP/ET group also had significantly more composite endpoints (HR 2.30, 95% CI 1.35–3.89, p=0.002) and heart failure hospitalizations (HR 7.55, 95% CI 2.88–19.79, p<0.001) after adjustment. In contrast, in the NT-proBNP ≥300 pg/mL group, there were no significant differences for the composite endpoint (HR 0.91, 95% CI 0.57–1.47, p=0.697) or heart failure hospitalization (HR 1.02, 95% CI 0.51–2.04, p=0.958) (Figure).

Conclusions

A high PEP/ET ratio was associated with an increased risk of cardiovascular events, including heart failure, and with reduced cardiac function. These findings suggest that elevated PEP/ET may help identify patients with latent heart failure, particularly among those with NT-proBNP <300 pg/mL.Figure