# Pulmonary Mechanisms of Dyspnea in HFpEF: Impact of Obesity

> **NIH NIH P01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $391,489

## Abstract

Dyspnea on exertion (DOE) and exercise intolerance are hallmark symptoms of heart failure with preserved ejection
fraction (HFpEF). The mechanisms of these two symptoms are unknown. Potential mechanisms for DOE are
numerous and multifactorial, including pulmonary limitations, exercise ventilatory limitations, central cardiovascular
limitations, peripheral vascular/muscle limitations, autonomic control alterations, and lastly obesity. Obesity
decreases lung volume subdivisions and exaggerates the age-related decline in maximal expiratory flow increasing
the risk of expiratory flow limitation and dynamic hyperinflation during exercise, both responses associated with
DOE. Obesity also increases the energy requirement of exercise, ventilatory demand, the work of breathing, and
exercise intolerance; all these alterations can also influence DOE. Indeed, one third of obese adults experience
DOE and many HFpEF patients are obese. DOE can be attenuated in adults by exercise training due to ‘sensory
adaptation. However, the effect of obesity in HFpEF patients is underappreciated, in contrast to conventional
thinking, which assumes that increased pulmonary capillary wedge pressure (PCW) is responsible. The overall
objective of Project 4 is to investigate the mechanisms of DOE and exercise intolerance in obese and
nonobese HFpEF patients. Aim 1) We will examine the interaction of obesity (obesity-related alterations in
pulmonary function & body composition including abdominal fat) and HFpEF (underlying changes in lung function)
on ventilatory reserves at rest and during submaximal cycling exercise, and their associations (if any) with DOE and
exercise intolerance in obese HFpEF patients as compared with nonobese HFpEF patients, and obese and
nonobese patients without HFpEF. We hypothesize that breathing limitations due to obesity and HFpEF will
combine to limit ventilatory reserves during exercise, which will provoke greater DOE and exercise intolerance in
the obese HFpEF patients; Aim 2) We will investigate the effects of pulmonary vascular function (including the
effects of decreased PCW via sublingual nitroglycerin, SL TNG, treatment,) on DOE and exercise tolerance during
submaximal constant load cycling exercise (& during MR imaging for lung water content). We hypothesize that
DOE may not be decreased as much by SL TNG treatment in obese HFpEF patients as in nonobese HFpEF
patients since obesity-related respiratory limitations will not be altered by decreased PCW via SL TNG treatment;
and Aim 3) We will examine the effects of central and peripheral exercise limitations via endurance exercise
training coupled with SL TNG treatment (improved central cardiac function) and single leg kicking exercise training
(improved peripheral muscle/vascular function) on DOE and exercise tolerance in HFpEF patients during constant
load submaximal cycling exercise. We hypothesize that both central and peripheral exercise training will decrease
DOE to a greater extent in o...

## Key facts

- **NIH application ID:** 9869940
- **Project number:** 5P01HL137630-02
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** TONY G BABB
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $391,489
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869940

## Citation

> US National Institutes of Health, RePORTER application 9869940, Pulmonary Mechanisms of Dyspnea in HFpEF: Impact of Obesity (5P01HL137630-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9869940. Licensed CC0.

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