Peripheral harmonic distortion metrics derived from photoplethysmography are associated with left ventricular ejection fraction in a cardiology cohort

In assessing systolic function, left ventricular ejection fraction (LVEF) remains the chief clinical metric; however, population-wide screening relies primarily on resource-intensive and not easily scalable imaging modalities. Widely available in wearable devices and outpatient care, peripheral photoplethysmography (PPG) captures pulse waveform morphology determined by ventricular ejection and arterial load. Currently, harmonic-domain PPG characteristics reflecting variations in systolic performance remain uncertain. This cross-sectional study aimed to investigate the association of peripheral PPG-derived morphological and harmonic distortion metrics with LVEF in real-world outpatients with cardiovascular conditions. In total, 1,126 participants underwent standardized finger PPG recording and clinical echocardiographic assessment of LVEF. After signal-quality filtering, we extracted time-domain features (area, P1, AC/DC, Std_AREA) and harmonic ratios (H2/H1, H3/H1). Associations with LVEF were evaluated using Spearman correlation and multivariable linear regression. To evaluate domain-level contributions, we conducted block regression and dominance analyses. Several PPG-derived features demonstrated statistically significant but modest associations with LVEF. Exploratory multivariable analyses identified both amplitude-based and harmonic-domain parameters as candidate contributors to systolic function. To further address potential confounding and model instability, additional covariate-adjusted and collinearity analyses were performed. After adjustment for major clinical covariates, H2/H1 remained independently associated with LVEF and demonstrated no severe multicollinearity in VIF analysis. In block modeling, harmonic-domain features showed modestly greater explanatory contribution than amplitude-based parameters. However, H2/H1 was not significant in univariable correlation analysis and showed only a small association after multivariable adjustment. Therefore, peripheral PPG waveform features demonstrated systematic associations with LVEF in outpatients with cardiologic conditions. Harmonic redistribution metrics may reflect ventricular–arterial interaction beyond simple pulse amplitude transmission. Given the small effect sizes and low model explanatory power, these findings should be interpreted as exploratory associations rather than evidence that harmonic distortion is a clinically useful marker of LVEF or systolic–vascular coupling. These findings suggest that harmonic distortion metrics derived from peripheral PPG may contain limited complementary physiological information associated with LVEF and warrant prospective validation using contemporaneous measurements.