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The impact of obesity on left ventricular hypertrophy and diastolic dysfunction in children and adolescents.

ABSTRACT: Childhood obesity continues to escalate worldwide and may affect left ventricular (LV) geometry and function. The aim of this study was to investigate the impact of obesity on prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction in children. In this analysis of prospectively collected cross-sectional data of children between 5 and 16 years of age from randomly selected schools in Peru, parameters of LV geometry and function were compared according to presence or absence of obesity (body mass index z-score > 2). LVH was based on left ventricular mass index (LVMI) adjusted for age and sex and defined by a z-score of > 2. LV diastolic function was assessed using mitral inflow early-to-late diastolic flow (E/A) ratio, peak early diastolic tissue velocities of the lateral mitral annulus (E'), early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity (E/E') ratio, and left atrial volume index (LAVI). Among 1023 children, 681 children (mean age 12.2 ± 3.1 years, 341 male (50.1%)) were available for the present analysis, of which 150 (22.0%) were obese. LVH was found in 21 (14.0%) obese and in 19 (3.6%) non-obese children (p_adjusted < 0.001). LVMI was greater in obese than that in non-obese children (36.1 ± 8.6 versus 28.7 ± 6.9 g/m^2.7, p < 0.001). The mean mitral E/E' ratio and LAVI were significantly higher in obese than those in non-obese individuals (E/E': 5.2 ± 1.1 versus 4.9 ± 0.8, p_adjusted = 0.043; LAVI 11.0 ± 3.2 versus 9.6 ± 2.9, p_adjusted = 0.001), whereas E' and E/A ratio were comparable. Childhood obesity was associated with left ventricular hypertrophy and determinants of diastolic dysfunction.ClinicalTrials.gov Identifier: NCT02353663.

SUBMITTER: Bartkowiak J

PROVIDER: S-EPMC8219764 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AimsConcentric hypertrophy following pressure-overload is linked to preserved systolic function but impaired diastolic function, and is an important substrate for heart failure with preserved ejection fraction. While increased passive stiffness of the myocardium is a suggested mechanism underlying diastolic dysfunction in these hearts, the contribution of active diastolic Ca2+ cycling in cardiomyocytes remains unclear. In this study, we sought to dissect contributions of passive and active mechanisms to diastolic dysfunction in the concentrically hypertrophied heart following pressure-overload.Methods and resultsRats were subjected to aortic banding (AB), and experiments were performed 6 weeks after surgery using sham-operated rats as controls. In vivo ejection fraction and fractional shortening were normal, confirming preservation of systolic function. Left ventricular concentric hypertrophy and diastolic dysfunction following AB were indicated by thickening of the ventricular wall, reduced peak early diastolic tissue velocity, and higher E/e' values. Slowed relaxation was also observed in left ventricular muscle strips isolated from AB hearts, during both isometric and isotonic stimulation, and accompanied by increases in passive tension, viscosity, and extracellular collagen. An altered titin phosphorylation profile was observed with hypophosphorylation of the phosphosites S4080 and S3991 sites within the N2Bus, and S12884 within the PEVK region. Increased titin-based stiffness was confirmed by salt-extraction experiments. In contrast, isolated, unloaded cardiomyocytes exhibited accelerated relaxation in AB compared to sham, and less contracture at high pacing frequencies. Parallel enhancement of diastolic Ca2+ handling was observed, with augmented NCX and SERCA2 activity and lowered resting cytosolic [Ca2+].ConclusionIn the hypertrophied heart with preserved systolic function, in vivo diastolic dysfunction develops as cardiac fibrosis and alterations in titin phosphorylation compromise left ventricular compliance, and despite compensatory changes in cardiomyocyte Ca2+ homeostasis.

Project description:PurposeTo assess the impact of left ventricular (LV) diastolic dysfunction on left atrial (LA) phasic volume and function using dual-source CT (DSCT) and to find a viable alternative prognostic parameter of CT for LV diastolic dysfunction through quantitative evaluation of LA phasic volume and function in patients with LV diastolic dysfunction.Materials and methodsSeventy-seven patients were examined using DSCT and Doppler echocardiography on the same day. Reservoir, conduit, and contractile function of LA were evaluated by measuring LA volume (LAV) during different cardiac phases and all parameters were normalized to body surface area (BSA). Patients were divided into four groups (normal, impaired relaxation, pseudonormal, and restrictive LV diastolic filling) according to echocardiographic findings. The LA phasic volume and function in different stages of LV diastolic function was compared using one-way ANOVA analysis. The correlations between indexed volume of LA (LAVi) and diastolic function in different stages of LV were evaluated using Spearman correlation analysis.ResultsLA ejection fraction (LAEF), LA contraction, reservoir, and conduit function in patients in impaired relaxation group were not different from those in the normal group, but they were lower in patients in the pseudonormal and restrictive LV diastolic dysfunction groups (P < 0.05). For LA conduit function, there were no significant differences between the patients in the pseudonormal group and restrictive filling group (P = 0.195). There was a strong correlation between the indexed maximal left atrial volume (LAVmax, r = 0.85, P < 0.001), minimal left atrial volume (LAVmin, r = 0.91, P < 0.001), left atrial volume at the onset of P wave (LAVp, r = 0.84, P < 0.001), and different stages of LV diastolic function. The LAVi increased as the severity of LV diastolic dysfunction increased.ConclusionsLA remodeling takes place in patients with LV diastolic dysfunction. At the same time, LA phasic volume and function parameters evaluated by DSCT indicated the severity of the LV diastolic dysfunction. Quantitative analysis of LA phasic volume and function parameters using DSCT could be a viable alternative prognostic parameter of LV diastolic function.

Project description:BackgroundPatients with chronic kidney disease (CKD) and coincident heart failure with preserved ejection fraction (HFpEF) may constitute a distinct HFpEF phenotype. Osteopontin (OPN) is a biomarker of HFpEF and predictive of disease outcome. We recently reported that OPN blockade reversed hypertension, mitochondrial dysfunction, and kidney failure in Col4a3-/- mice, a model of human Alport syndrome.ObjectivesThe purpose of this study was to identify potential OPN targets in biopsies of HF patients, healthy control subjects, and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs), and to characterize the cardiac phenotype of Col4a3-/- mice, relate this to HFpEF, and investigate possible causative roles for OPN in driving the cardiomyopathy.MethodsOGDHL mRNA and protein were quantified in myocardial samples from patients with HFpEF, heart failure with reduced ejection fraction, and donor control subjects. OGDHL expression was quantified in hiPS-CMs treated with or without anti-OPN antibody. Cardiac parameters were evaluated in Col4a3-/- mice with and without global OPN knockout or AAV9-mediated delivery of 2-oxoglutarate dehydrogenase-like (Ogdhl) to the heart.ResultsOGDHL mRNA and protein displayed abnormal abundances in cardiac biopsies of HFpEF (n = 17) compared with donor control subjects (n = 12; p < 0.01) or heart failure with reduced ejection fraction patients (n = 12; p < 0.05). Blockade of OPN in hiPS-CMs conferred increased OGDHL expression. Col4a3-/- mice demonstrated cardiomyopathy with similarities to HFpEF, including diastolic dysfunction, cardiac hypertrophy and fibrosis, pulmonary edema, and impaired mitochondrial function. The cardiomyopathy was ameliorated by Opn-/- coincident with improved renal function and increased expression of Ogdhl. Heart-specific overexpression of Ogdhl in Col4a3-/- mice also improved cardiac function and cardiomyocyte energy state.ConclusionsCol4a3-/- mice present a model of HFpEF secondary to CKD wherein OPN and OGDHL are intermediates, and possibly therapeutic targets.

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The impact of obesity on left ventricular hypertrophy and diastolic dysfunction in children and adolescents.

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