In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 129, No. Suppl_1 ( 2021-09-03)
Kurzfassung:
Rationale: Heart Failure with preserved Ejection Fraction (HFpEF) accounts for approximately 50% of all HF diagnoses with no FDA approved therapies. HFpEF is more prevalent in females versus males, but the mechanisms driving the development of HFpEF as a sex-based disorder are not well understood. We have recently shown that slow progressive pressure overload (PO) in male felines induces a HFpEF phenotype but have not investigated the differences in response to the same physiological stress in females. Hypothesis: Females will develop a phenotype that is distinct from males in response to PO. Methods and Results: Male (m) and female (f) domestic short felines (age 2mo) underwent either a sham procedure (m: n=7; f: n=7) or aortic constriction (m: n=11; f: n=10) using a customized pre-shaped band. At baseline (prior to surgery), there was no difference in body weight between groups and echocardiography revealed no significant difference in the ratio of left atrium to aortic root (LA/Ao), LA ejection fraction (LA EF), left ventricle (LV) ejection fraction, LV wall-thickness, and E/A ratio. At 4mo post-surgery, both males and females developed cardiac dysfunction. Females gained significantly less weight than males throughout the study. Despite the size difference, both sexes developed comparable LV wall thickness and changes in E/A ratio vs. sham groups. There was no change in LV EF. Furthermore, there was a decrease in LA EF and increased LA/Ao, indicating LA dysfunction and enlargement. Invasive hemodynamics at 4mo post-surgery showed no differences between sexes for the systolic pressure gradient generated by the aortic banding. Banded males had a significantly higher LV end-diastolic pressure vs. banded females, but there was a trend towards prolongation of tau and lower dp/dt min in banded females, reflective of worse active relaxation. Both sexes had comparable dP/dt max . There were no differences between banded males and females in heart weight to body weight or cardiomyocyte cross-sectional area. Conclusion: Despite similar pressure gradients as a result of PO and the development of similar cardiac hypertrophy between sexes and a higher LVEDP in males, females had a trend towards worse relaxation. Other causes of HFpEF may have sex-based differences.
Materialart:
Online-Ressource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/res.129.suppl_1.P411
Sprache:
Englisch
Verlag:
Ovid Technologies (Wolters Kluwer Health)
Publikationsdatum:
2021
ZDB Id:
1467838-X
