Abstract

Fractal analysis provides a global assessment of vascular networks (e.g., geometric complexity). We examined the association of diastolic left ventricular (LV) function with the retinal microvascular fractal dimension. A lower fractal dimension signifies a sparser retinal microvascular network. In 628 randomly recruited Flemish individuals (51.3% women; mean age, 50.8 years), we measured diastolic LV function by echocardiography and the retinal microvascular fractal dimension by the box-counting method (Singapore I Vessel Assessment software, version 3.6). The left atrial volume index (LAVI), e′, E/e′ and retinal microvascular fractal dimension averaged (±SD) 24.3 ± 6.2 mL/m2, 10.9 ± 3.6 cm/s, 6.96 ± 2.2, and 1.39 ± 0.05, respectively. The LAVI, E, e′ and E/e′ were associated (P < 0.001) with the retinal microvascular fractal dimension with association sizes (per 1 SD), amounting to −1.49 mL/m2 (95% confidence interval, −1.98 to −1.01), 2.57 cm/s (1.31–3.84), 1.34 cm/s (1.07–1.60), and −0.74 (−0.91 to −0.57), respectively. With adjustments applied for potential covariables, the associations of E peak and E/e′ with the retinal microvascular fractal dimension remained significant (P ≤ 0.020). Over a median follow-up of 5.3 years, 18 deaths occurred. The crude and adjusted hazard ratios expressing the risk of all-cause mortality associated with a 1-SD increment in the retinal microvascular fractal dimension were 0.36 (0.23–0.57; P < 0.001) and 0.57 (0.34–0.96; P = 0.035), respectively. In the general population, a lower retinal microvascular fractal dimension was associated with greater E/e′, a measure of LV filling pressure. These observations can potentially be translated into new strategies for the prevention of diastolic LV dysfunction.

Highlights

  • Subclinical diastolic left ventricular (LV) dysfunction has a prevalence of 25% in the general population [4, 5], predisposes patients to further deterioration of LV function [6], and progresses to overt Heart failure (HF) [3]

  • To test the hypothesis that diastolic LV function might be related to microcirculatory dysfunction [7], we examined the association of echocardiographically assessed diastolic LV function with the retinal microvascular fractal dimension in a Flemish population study [13]

  • Assuming that the retinal microvasculature might provide a window representative of the myocardial microcirculation, the key finding of our study was that parameters of diastolic function, i.e., the Doppler-derived mitral inflow velocity (E peak) and mitral annular early diastolic velocity

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Summary

Introduction

50% of HF patients present with symptoms of diastolic dysfunction with preserved ejection fraction [3]. Subclinical diastolic left ventricular (LV) dysfunction has a prevalence of 25% in the general population [4, 5], predisposes patients to further deterioration of LV function [6], and progresses to overt HF [3]. Noninvasively phenotyping the myocardial microvasculature in populations is not practicable. The retinal microvasculature can be completely noninvasively [8] and reproducibly [9] assessed. Fractal analysis of the retinal microvasculature provides a global assessment of the complexity and density of small vessels [10]. A lower fractal dimension signifies a Diastolic left ventricular function in relation to the retinal microvascular fractal dimension in a

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