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Phenotyping RV-PA coupling across PH types in the PVDOMICS dataset

Award Number: R21HL184279
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: 08/14/2028

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Phenotyping RV-PA coupling across PH types in the PVDOMICS dataset - Project Summary Pulmonary hypertension (PH) is a progressive disease with a current 50% survival rate that has increased from 5 to 7 years due to therapeutic approaches. However, the complex pathophysiology of right heart failure poses an obstacle in developing meaningful right ventricular (RV) features for better assessment. At present, RV function is not incorporated in current risk assessment models in pulmonary arterial hypertension. Current risk models fail to differentiate between intermediate-risk patients, and identifying hemodynamic, clinical, and laboratory correlates of RV dysfunction is necessary for improved stratification. Additionally, studies evaluating RV function are generally limited to single-center studies and focus on one modality of assessment, either imaging or hemodynamics. The gold standard for assessing RV-PA coupling is conductance catheter multi- beat pressure-volume loops, but single-beat loops are more accessible in clinical settings. Refined sub- phenotypes of RV function are needed to personalize therapeutic strategies before overt systolic failure occurs, but access to datasets with deeply phenotyped patients is a major barrier. The PVDOMICS cohort includes extensively phenotyped patients with clinical characteristics, CMR imaging, and biospecimens to develop classifications by phenomes associated with pathogenesis mechanisms. We propose to move beyond current risk scores to identify novel RV phenotypes and endotypes across the PH spectrum. We will build on our previous success in quantifying RV function, risk stratification, and algorithm development to bring new tools into the high-impact area of risk stratification in PH. The proposed project will leverage the PVDOMICS cohort to phenotype RV dysfunction, including contractility, afterload, diastolic stiffness, and RV-PA coupling, through secondary analysis of right heart catheterization data. The goal is to identify phenotypes reflective of the PH patient spectrum and features of importance for each PH type, facilitating personalized PH management. We will quantify invasive single-beat RV-PA coupling across PH types. Secondarily we will use graphical Least Absolute Shrinkage and Selection Operator (glasso), Leiden communities and eXtreme Gradient Boosting (XGBoost) approaches to develop risk models that incorporate right ventricular function, and we hypothesize that they will outperform existing risk strategies across the PH spectrum. Improved characterization of outcomes according to RV function phenotypes may enhance therapy and treatment goal personalization for PH management. Aim 1 will focus on quantifying RV-PA coupling across the spectrum of PH using clinical pressure-volume loops and hemodynamic measures of RV function. Aim 2 will focus on the development of advanced risk models to predict clinical outcomes and identify clinically relevant right heart failure phenotypes.


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 = $236,250 )
2026	2026	OHIO STATE UNIVERSITY, THE	1960 KENNY RD	COLUMBUS	OH	43210	FRANKLIN	USA	Lung Diseases Research	000	1	8/7/2026	NEW	$236,250
														Subtotal = $236,250

Grand Total All Awards = $236,250

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Phenotyping RV-PA coupling across PH types in the PVDOMICS dataset

Award Number: R21HL184279

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: 08/14/2028

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