# Identifying Predictors of Spironolactone Response in Patients with Heart Failure with Preserved Ejection Fraction

> **NIH NIH F31** · UNIVERSITY OF FLORIDA · 2020 · $39,709

## Abstract

Project Summary/Abstract
 This Kirschstein NRSA Predoctoral Fellowship proposal aims to train the candidate to develop an
independent research career in public health genomics, using epidemiological methods to identify clinical and
genetic predictors of spironolactone response in patients with heart failure with preserved ejection fraction
(HFpEF). Public health genomics is an emerging field of study that uses genomic sciences, in addition to the
traditional correlates of disease, to improve population health and prevent disease. The training goals in this
application include: 1) enhancing genomic and epidemiological data analysis skills, 2) training in public health,
and 3) professional development; all preparing the candidate for a career on the translational front of preventive
and precision medicine.
 Given the increasing prevalence of HFpEF, together with limited evidence-based treatments, treatment of
HFpEF is considered one of the current, greatest unmet needs in cardiology. Studies show spironolactone, an
aldosterone receptor antagonist (ARA), has beneficial effects on cardiac fibrosis, blood pressure, and cardiac
remodeling, which contribute to HFpEF pathophysiology; however, its use in HFpEF management remains
underutilized because of mixed results observed in clinical trials. These mixed results have been attributable to
the significant heterogeneity seen in HFpEF etiology and pathophysiology and inter-patient differences in drug
response. Thus, the objective of this proposal is to identify factors and subgroups of patients most likely to
respond to ARA therapy or, conversely, at the greatest risk for toxicity with ARA therapy, thus informing
personalized therapy and potentially improving effectiveness and safety with spironolactone use in patients with
HFpEF.
 To achieve the objective of this proposal, the first aim is to identify genetic variants associated with
spironolactone response, both efficacy and safety, in patients with HFpEF. Data from a genome-wide association
study in the Aldosterone Receptor Blockade in Diastolic Heart Failure (Aldo-DHF) trial will be used to identify
these variants. The second aim is to identify clinical factors associated with spironolactone response, both
effectiveness and safety, in patients with HFpEF in a real-world setting. This analysis will be done using data
from the large health system’s electronic health records at the candidate’s institution, with predictors identified
using LASSO penalized regression models. The results of these studies could have an impact on the
management of patients with HFpEF, potentially providing new data to inform more personalized therapeutic
strategies. This proposal is in line with NHLBI’s objectives: 1) to optimize treatment of HFpEF and 2) to identify
phenotypic, biomarker, and molecular characteristics which predict differential responses to therapy in
individuals and in different populations with cardiovascular diseases.

## Key facts

- **NIH application ID:** 10066462
- **Project number:** 1F31HL154563-01
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Leanne Dumeny
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $39,709
- **Award type:** 1
- **Project period:** 2020-08-16 → 2022-01-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10066462

## Citation

> US National Institutes of Health, RePORTER application 10066462, Identifying Predictors of Spironolactone Response in Patients with Heart Failure with Preserved Ejection Fraction (1F31HL154563-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10066462. Licensed CC0.

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