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Diastolic left ventricular function in relation to the retinal microvascular fractal dimension in a Flemish population.

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.

SUBMITTER: Wei FF

PROVIDER: S-EPMC8019655 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Current knowledge on the pathogenesis of diastolic heart failure predominantly rests on case-control studies involving symptomatic patients with preserved ejection fraction and relying on invasive diagnostic procedures including endomyocardial biopsy. Our objective was to gain insight in serum and urinary biomarkers reflecting collagen turnover and associated with asymptomatic diastolic LV dysfunction. We randomly recruited 782 Flemish (51.3% women; 50.5 years). We assessed diastolic LV function from the early and late diastolic peak velocities of the transmitral blood flow and of the mitral annulus. By sequencing urinary peptides, we identified 70 urinary collagen fragments. In serum, we measured carboxyterminal propeptide of procollagen type 1 (PICP) as marker of collagen I synthesis and tissue inhibitor of matrix metalloproteinase type 1 (TIMP-1), an inhibitor of collagen-degrading enzymes. In multivariable-adjusted analyses with Bonferroni correction, we expressed effect sizes per 1-SD in urinary collagen I (uCI) or collagen III (uCIII) fragments. In relation to uCI fragments, e' decreased by 0.183 cm/s (95% confidence interval, 0.017 to 0.350; p = 0.025), whereas E/e' increased by 0.210 (0.067 to 0.353; p = 0.0012). E/e' decreased with uCIII by 0.168 (0.021 to 0.316; p = 0.018). Based on age-specific echocardiographic criteria, 182 participants (23.3%) had subclinical diastolic LV dysfunction. Partial least squares discriminant analysis contrasting normal vs. diastolic LV dysfunction confirmed the aforementioned associations with the uCI and uCIII fragments. PICP and TIMP-1 increased in relation to uCI (p<0.0001), whereas these serum markers decreased with uCIII (p?0.0006). Diastolic LV dysfunction was associated with higher levels of TIMP-1 (653 vs. 696 ng/mL; p = 0.013). In a general population, the non-invasively assessed diastolic LV function correlated inversely with uCI and serum markers of collagen I deposition, but positively with uCIII. These observations generalise previous studies in patients to randomly recruited people, in whom diastolic LV function ranged from normal to subclinical impairment, but did not encompass overt diastolic heart failure.

Project description:An early manifestation of coronary artery disease in advanced age is the development of microvascular dysfunction leading to deficits in diastolic function. Our lab has previously shown that epicardial treatment with adipose-derived stromal vascular fraction (SVF) preserves microvascular function following coronary ischemia in a young rodent model. Follow-up studies showed intravenous (i.v.) delivery of SVF allows the cells to migrate to the walls of small vessels and reset vasomotor tone. Therefore we tested the hypothesis that the i.v. cell injection of SVF would reverse the coronary microvascular dysfunction associated with aging in a rodent model. Fischer 344 rats were divided into 4 groups: young control (YC), old control (OC), old + rat aortic endothelial cells (O+EC) and old + GFP+ SVF cells (O+SVF). After four weeks, cardiac function and coronary flow reserve (CFR) were measured via echocardiography, and hearts were explanted either for histology or isolation of coronary arterioles for vessel reactivity studies. In a subgroup of animals, microspheres were injected during resting and dobutamine-stimulated conditions to measure coronary blood flow. GFP+ SVF cells engrafted and persisted in the myocardium and coronary vasculature four weeks following i.v. injection. Echocardiography showed age-related diastolic dysfunction without accompanying systolic dysfunction; diastolic function was improved in old rats after SVF treatment. Ultrasound and microsphere data both showed increased stimulated coronary blood flow in O+SVF rats compared to OC and O+EC, while isolated vessel reactivity was mostly unchanged. I.v.-injected SVF cells were capable of incorporating into the vasculature of the aging heart and are shown in this study to improve CFR and diastolic function in a model of advanced age. Importantly, SVF injection did not lead to arrhythmias or increased mortality in aged rats. SVF cells provide an autologous cell therapy option for treatment of microvascular and cardiac dysfunction in aged populations.

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Diastolic left ventricular function in relation to the retinal microvascular fractal dimension in a Flemish population.

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