R01HL158077

Cardiopulmonary Exercise MRI in Heart Failure with Preserved Ejection Fraction - Project Summary

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States, with the prevalence of heart failure with preserved ejection fraction (HFPEF) rising every year. Currently, there is no single non-invasive diagnostic test for accurate diagnosis of HFPEF. HFPEF is diagnosed through a combination of symptom assessments, plasma biomarkers, and cardiac imaging. When patients are acutely decompensated, HFPEF can be diagnosed with high confidence. However, among stable outpatients presenting with dyspnea on exertion and an intermediate pre-test probability of HFPEF, diagnosis is extremely challenging.

Since non-invasive testing has limited diagnostic specificity, in these cases, invasive hemodynamic cardiopulmonary exercise testing (ICPET) is considered the gold standard. However, ICPET is invasive, carries risk, and is performed only in specialized centers. Cardiovascular MRI (CMR) can non-invasively assess HF-related heart and vascular abnormalities including biventricular structure/function, myocardial tissue composition, coronary microvascular function, aortic distensibility/stiffness, and fat accumulation.

As cardiovascular and pulmonary symptoms of HFPEF occur with exertion, the objective of this proposal is to use a supine ergometer mounted on the MRI scanner table to examine heart and lung pathophysiology with exercise of incrementally increasing resistance, followed by a conventional vasodilator stress imaging protocol. The goal of this study is to use our novel cardiopulmonary exercise MRI protocol to accurately diagnose "early" HFPEF, to eliminate the need for ICPET, and to identify specific pathophysiologies underlying HFPEF progression and prognostic information for adverse CVD outcomes.

To achieve this, we will recruit patients from three medical centers to conduct a prospective study using cardiopulmonary exercise MRI in suspected "early" HFPEF patients who are clinically referred for ICPET, with a follow-up MRI scan 18 months later. Our three specific aims seek to:

1) Investigate non-invasive imaging correlates and diagnostic performance of cardiopulmonary MRI for early HFPEF diagnosis in patients with normal ejection fraction and unexplained dyspnea, using ICPET as a reference standard.

2) Investigate the relationship between cardiopulmonary exercise MRI parameters and CVD health outcomes, including cardiovascular death and hospitalization in suspected early HFPEF.

3) Explore temporal changes in heart and lung structure and function in suspected early HFPEF by completing a second cardiopulmonary exercise MRI 18 months after the initial MRI exam.

This innovative cardiopulmonary exercise MRI protocol is expected to improve non-invasive diagnosis and prognosis of HFPEF, and ultimately contribute to improved treatment strategies and preventative care by providing more accurate diagnostic criteria and a non-invasive method of monitoring the efficacy of new treatment strategies in clinical trials.

Beth Israel Deaconess Medical Center

TO FOSTER HEART AND VASCULAR RESEARCH IN THE BASIC, TRANSLATIONAL, CLINICAL AND POPULATION SCIENCES, AND TO FOSTER TRAINING TO BUILD TALENTED YOUNG INVESTIGATORS IN THESE AREAS, FUNDED THROUGH COMPETITIVE RESEARCH TRAINING GRANTS. SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, USE SMALL BUSINESS TO MEET FEDERAL RESEARCH AND DEVELOPMENT NEEDS, FOSTER AND ENCOURAGE PARTICIPATION IN INNOVATION AND ENTREPRENEURSHIP BY SOCIALLY AND ECONOMICALLY DISADVANTAGED PERSONS, AND INCREASE PRIVATE-SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT FUNDING. SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM: TO STIMULATE TECHNOLOGICAL INNOVATION, FOSTER TECHNOLOGY TRANSFER THROUGH COOPERATIVE R&D BETWEEN SMALL BUSINESSES AND RESEARCH INSTITUTIONS, AND INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL R&D.

93.837 - Cardiovascular Diseases Research

National Heart Lung and Blood Institute (NHLBI) [HHS - NIH]

Boston, Massachusetts 022155400 United States

Single Zip Code

NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed) (PA-20-185)

Amendment Since initial award the total obligations have increased 373% from $783,751 to $3,703,807.