# Altered Energy Metabolism in Human Heart Failure

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $601,962

## Abstract

Over half of HF patients today have a preserved ejection fraction (HFpEF) and so we now turn our
attention in HL61912 to HFpEF because of its growing prevalence, high mortality, exorbitant costs, poorly
understood pathophysiology, and the lack of a proven treatment. Because there are no accepted HFpEF
animal models, mechanistic human studies are needed to identify and understand the factors that contribute to
this systemic, global process that results in profound exercise intolerance (EI).
 We present new data here that HFpEF patients manifest significant abnormalities in both cardiac and
skeletal muscle high-energy phosphate (HEP) metabolism and propose to determine their relationship to EI
and clinical HF symptoms as well as disease progression for the first time in HFpEF patients. This proposal will
exploit three new state-of-the-art noninvasive tools developed by the investigators and not available elsewhere
in the US to quantify a) myocardial energy metabolism and energetic reserve at rest, b) skeletal muscle energy
metabolism with a newly developed skeletal muscle energetic fatigability test, and c) nitric oxide-mediated
coronary endothelial function (CEF). The main premise of this work is that energetic abnormalities in cardiac
and/or skeletal muscle, potentially worsened by abnormal endothelial function, contribute independently to the
development of exercise intolerance and predict subsequent heart failure hospitalizations and cardiovascular
deaths. Thus the new in vivo metabolic findings will be related to established, conventional clinical HF indices,
diastolic function, biomarkers, and objective measures of exercise intolerance in both cross-sectional and
longitudinal fashion (6 months). Moreover, we will determine whether abnormal cardiac and/or skeletal muscle
energetics independently predict exercise intolerance and heart failure clinical outcomes over 2 years. A broad
investigative approach is important because HFpEF pathophysiology is thought to involve several interrelated
systems (including diastolic dysfunction, vascular/endothelial dysfunction, peripheral mechanisms, and
impaired energetics). These unique physiologic studies of myocardial, skeletal and coronary vascular changes
promise to guide new diagnostic/phenotyping approaches in HFpEF, uncover critical relationships and
mechanisms in HFpEF, termed by experts as the number one unmet need in cardiovascular medicine today.

## Key facts

- **NIH application ID:** 9899285
- **Project number:** 5R01HL061912-18
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** ROBERT G WEISS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $601,962
- **Award type:** 5
- **Project period:** 1999-07-19 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9899285

## Citation

> US National Institutes of Health, RePORTER application 9899285, Altered Energy Metabolism in Human Heart Failure (5R01HL061912-18). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9899285. Licensed CC0.

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