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Right Heart Cardiac Magnetic Resonance Tissue Characterization for Clinical and Therapeutic Prognostication in Functional Tricuspid Regurgitation

Award Number: R01HL183658
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/15/2026
PERIOD OF PERFORMANCE END DATE: 07/31/2031

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Right Heart Cardiac Magnetic Resonance Tissue Characterization for Clinical and Therapeutic Prognostication in Functional Tricuspid Regurgitation - PROJECT SUMMARY / ABSTRACT Tricuspid regurgitation (TR) is a leading cause of valvular disease. Nearly 2 million Americans have advanced (≥moderate) TR in the absence of intrinsic tricuspid valve pathology (functional TR [fTR]), in whom the risk for heart failure doubles and mortality risk triples. Despite its clinical significance, current risk stratification based on regur- gitation severity and right ventricular (RV) function is insufficient: one quarter of patients progress rapidly (mild to severe TR within 1.2 years) while others remain stable for years, yet conventional indices fail to distinguish these trajectories. Similarly, response to percutaneous repair is heterogeneous and predictors of therapeutic benefit re- main undefined. Knowledge gaps regarding the pathogenesis, progression, and prognosis of fTR are highly time- sensitive with the advent of percutaneous therapies that have fundamentally reshaped its treatment landscape. A critical challenge in TR management is distinguishing adverse outcomes driven by valvular regurgitation from those caused by underlying RV tissue abnormalities. The central hypothesis is that myocardial tissue injury (fibrosis, impaired oxygenation) drives TR progression and therapeutic response, independent of traditional right-sided func- tional indices. This substrate-driven paradigm shifts focus from descriptive functional assessment to mechanistic tissue characterization. To test this hypothesis, we will utilize newly developed cardiac magnetic resonance (CMR) techniques optimized for the thin-walled RV: (1) high resolution 3D navigator LGE-CMR with sub-millimeter reso- lution for focal and diffuse fibrosis, and (2) quantitative susceptibility mapping (QSM) for blood oxygenation, a novel physiologic index of RV performance our team has developed and validated. Our preliminary data indicate that CMR tissue characterization (fibrosis, oxygenation) predicts prognosis in patients at risk for TR, supporting the research premise. To systematically test the utility of right heart tissue characterization, we will prospectively study ≥265 patients with advanced fTR (Aims 1 and 2) and ≥60 patients undergoing percutaneous TriClip derived from two NYC institutions (Cornell, Columbia) that share a common hospital infrastructure (NewYork-Presbyterian Hos- pital). Rigorous follow-up will incorporate quality of life metrics, effort tolerance assessments, and clinical outcomes, including heart failure hospitalization and mortality. Aim 1 will test whether RV injury (3D LGE, extracellular volume mapping) will predict adverse RV remodeling and TR progression. Aim 2 will test whether impaired RV oxygenation (QSM) will stratify functional status better than conventional indices of RV function. Aim 3 tests whether baseline RV tissue injury and impaired oxygenation can identify predictors of response to percutaneous tricuspid valve re- pair. Our team brings complementary expertise in TR-focused outcomes research, CMR physics, and structural heart disease, along with a track record of productive collaboration. Results of this R01 will (1) establish myocardial injury and oxygenation as mechanistic, quantifiable drivers of fTR progression and outcomes; (2) yield scalable imaging biomarkers (LGE, QSM, and echo surrogates) for clinical use; and (3) inform optimal timing and selection of tricuspid interventions, ultimately improving outcomes for millions of patients with fTR.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $704,851 )
2026	2026	WEILL MEDICAL COLLEGE OF CORNELL UNIVERSITY	575 LEXINGTON AVE FL 9	NEW YORK	NY	10022	NEW YORK	USA	Cardiovascular Diseases Research	000	1	8/11/2026	NEW	$704,851
														Subtotal = $704,851

Grand Total All Awards = $704,851

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Right Heart Cardiac Magnetic Resonance Tissue Characterization for Clinical and Therapeutic Prognostication in Functional Tricuspid Regurgitation

Award Number: R01HL183658

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/15/2026

PERIOD OF PERFORMANCE END DATE: 07/31/2031

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