# Ventricular-vascular coupling in the elderly: lifecourse determinants, trajectories and prognostic significance

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2020 · $793,239

## Abstract

Abstract
Aortic stiffness increases markedly with age and is associated with hypertension, heart failure and accelerated
brain aging. Abnormal hemodynamic coupling between left ventricle (LV) and aorta contributes to
pathogenesis of target organ damage. However, the LV is also mechanically coupled to and stretches the
proximal aorta during systole. The force associated with stretch of the `aortic spring' is considerable,
comparable to the force required for LV pressure generation. `Mechanical coupling' loads the LV but also
stores energy in the aortic spring, which contributes to the recoil of the base of the heart during diastole,
producing the suction that facilitates early diastolic filling. Aortic stiffening disrupts this mechanical coupling
and imposes an asymmetric load on the LV long axis that impairs global longitudinal strain (GLS) and early
diastolic filling. Impaired mechanical coupling contributes to left atrial (LA) enlargement and dysfunction, which
increases pulmonary artery (PA) pressure and stiffness, leading to abnormal right ventricular (RV)-PA
hemodynamic coupling, and an age-related increase in PA systolic pressure. An associated increase in PA
pulse pressure could contribute to remodeling of resistance vessels in the lung, leading to combined pre- and
post-capillary pulmonary hypertension. The resulting combination of right and left heart abnormalities limits
cardiac output and contributes to the syndrome of heart failure with preserved LV ejection fraction (HFpEF). In
young, healthy adults, the low impedance of a compliant aorta interfaces with normally stiff conduit arteries,
creating impedance mismatch and wave reflection that limits the transmission of excessive pulsatile energy
into the microcirculation, resulting in optimal `hemodynamic coupling' between the left heart and target organs,
such as the brain. Aortic stiffening increases aortic impedance, reduces impedance mismatch, and results in
an increased transmission of harmful pulsatile energy into the microcirculation, resulting in microvascular
damage, accumulation of amyloid fibrils in brain parenchyma, premature brain aging and cognitive impairment.
We will use tonometry and echocardiography in the elderly Framingham Offspring cohort to test the
hypothesis that aortic stiffness impairs mechanical coupling between the aorta and LV, reduces LV GLS and
impairs LV diastolic function and LA function. We will assess RV structure and function and RV-PA coupling
with echocardiography to test the hypothesis that an increase in LA pressure increases PA pressure, stiffness
and impedance, impairs RV-PA coupling and contributes to the age-related increase in pulmonary artery
systolic pressure. Finally, we will assess carotid input impedance and aorta-carotid coupling to test the
hypothesis that a disproportionate increase in aortic as compared to common carotid and cerebrovascular
input impedances reduces the impedance gradient and increases penetration of pulsatile flow int...

## Key facts

- **NIH application ID:** 9890919
- **Project number:** 5R01HL142983-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Susan Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $793,239
- **Award type:** 5
- **Project period:** 2019-04-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890919

## Citation

> US National Institutes of Health, RePORTER application 9890919, Ventricular-vascular coupling in the elderly: lifecourse determinants, trajectories and prognostic significance (5R01HL142983-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9890919. Licensed CC0.

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