Dataset Information

Biventricular adaptation to volume overload in mice with aortic regurgitation.

ABSTRACT:

Background

Aortic valve regurgitation is usually caused by impaired coaptation of the aortic valve cusps during diastole. Hypercholesterolemia produces aortic valve lipid deposition, fibrosis, and calcification in both mice and humans, which could impair coaptation of cusps. However, a link between hypercholesterolemia and aortic regurgitation has not been established in either species. The purpose of this study was to ascertain the prevalence of aortic regurgitation in hypercholesterolemic mice and to determine its impact on the left and right ventricles.

Methods and results

Eighty Ldlr-/-/Apob100/100/Mttpfl/fl/Mx1Cre+/+ ("Reversa") hypercholesterolemic mice and 40 control mice were screened for aortic regurgitation (AR) with magnetic resonance imaging at age 7.5 months. The prevalence of AR was 40% in Reversa mice, with moderate or severe regurgitation (AR+) in 19% of mice. In control mice, AR prevalence was 13% (p = 0.004 vs. Reversa), and was invariably trace or mild in severity. In-depth evaluation of cardiac response to volume overload was performed in 12 AR-positive and 12 AR-negative Reversa mice. Regurgitant fraction was 0.34 +/- 0.04 in AR-positive vs. 0.02 +/- 0.01 in AR-negative (mean +/- SE; p < 0.001). AR-positive mice had significantly increased left ventricular end-diastolic volume and mass and reduced ejection fraction in both ventricles. When left ventricular ejection fraction fell below 0.60 in AR-positive (n = 7) mice, remodeling occurred and right ventricular systolic function progressively worsened.

Conclusion

Hypercholesterolemia causes aortic valve regurgitation with moderate prevalence in mice. When present, aortic valve regurgitation causes volume overload and pathological remodeling of both ventricles.

SUBMITTER: Berry CJ

PROVIDER: S-EPMC2731737 | biostudies-literature | 2009 Aug

REPOSITORIES: biostudies-literature

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Publications

Biventricular adaptation to volume overload in mice with aortic regurgitation.

Berry Christopher J CJ Miller Jordan D JD McGroary KellyAnn K Thedens Daniel R DR Young Stephen G SG Heistad Donald D DD Weiss Robert M RM

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 20090811

<h4>Background</h4>Aortic valve regurgitation is usually caused by impaired coaptation of the aortic valve cusps during diastole. Hypercholesterolemia produces aortic valve lipid deposition, fibrosis, and calcification in both mice and humans, which could impair coaptation of cusps. However, a link between hypercholesterolemia and aortic regurgitation has not been established in either species. The purpose of this study was to ascertain the prevalence of aortic regurgitation in hypercholesterole ...[more]

PMID: 19671155

Similar Datasets

Project description:ImportanceVolumetric measurements by transthoracic echocardiogram may better reflect left ventricular (LV) remodeling than conventional linear LV dimensions. However, the association of LV volumes with mortality in patients with chronic hemodynamically significant aortic regurgitation (AR) is unknown.ObjectiveTo assess whether LV volumes and volume-derived LV ejection fraction (Vol-LVEF) are determinants of mortality in AR.Design, setting, and participantsThis cohort study included consecutive asymptomatic patients with chronic moderately severe to severe AR from a tertiary referral center (January 2004 through April 2019).ExposuresClinical and echocardiographic data were analyzed retrospectively. Aortic regurgitation severity was graded by comprehensive integrated approach. De novo disk-summation method was used to derive LV volumes and Vol-LVEF.Main outcome and measuresAssociations between all-cause mortality under medical surveillance and the following LV indexes: linear LV end-systolic dimension index (LVESDi), linear LVEF, LV end-systolic volume index (LVESVi), and Vol-LVEF.ResultsOf 492 asymptomatic patients (mean [SD] age, 60 [17] years; 425 men [86%]), ischemic heart disease prevalence was low (41 [9%]), and 453 (92.1%) had preserved linear LVEF (≥50%) with mean (SD) LVESVi of 41 (15) mL/m2. At a median (interquartile range) of 5.4 (2.5-10.1) years, 66 patients (13.4%) died under medical surveillance; overall survival was not different than the age- and sex-matched general population (P = .55). Separate multivariate models, adjusted for age, sex, Charlson Comorbidity Index, and AR severity, demonstrated that in addition to linear LVEF and LVESDi, LVESVi and Vol-LVEF were independently associated with mortality under surveillance (all P < .046) with similar C statistics (range, 0.83-0.84). Spline curves showed that continuous risks of death started to rise for both linear LVEF and Vol-LVEF less than 60%, LVESVi more than 40 to 45 mL/m2, and LVESDi above 21 to 22 mm/m2. As dichotomized variables, patients with LVESVi more than 45 mL/m2 exhibited increased relative death risk (hazard ratio, 1.93; 95% CI, 1.10-3.38; P = .02) while LVESDi more than 20 mm/m2 did not (P = .32). LVESVi more than 45 mL/m2 showed a decreased survival trend compared with expected population survival.Conclusions and relevanceIn this large asymptomatic cohort of patients with hemodynamically significant AR, LVESVi and Vol-LVEF worked equally as well as LVESDi and linear LVEF in risk discriminating patients with excess mortality. A LVESVi threshold of 45 mL/m2 or greater was significantly associated with an increased mortality risk.

Dataset Information

Biventricular adaptation to volume overload in mice with aortic regurgitation.

Background

Methods and results

Conclusion

Publications

Biventricular adaptation to volume overload in mice with aortic regurgitation.

Similar Datasets

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