# Blockade of calcium channels and beta adrenergic receptors for physiologic abnormalities in heart failure with preserved ejection fraction (BLOCK HFpEF)

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $622,706

## Abstract

PROJECT SUMMARY
Heart failure with preserved ejection fraction (HFpEF) is a critical public health problem. Heart failure (HF)
affects over 5 million adults in the United States (US), and is a major source of morbidity, mortality, and
impaired quality of life. Approximately half of individuals with HF have a preserved left ventricular (LV) ejection
fraction (EF), termed HF with preserved EF (HFpEF). While there are several effective pharmacologic
therapies for HF with reduced ejection fraction (HFrEF), none have been identified for HFpEF. There is an
urgent need to identify therapies that target mechanisms of pathophysiologic progression of HFpEF.
Hypertension, which is present in approximately 80% of individuals with HFpEF, is the foremost modifiable risk
factor for the development and progression of HFpEF. Despite the clinical importance of hypertension in
HFpEF, there is limited information on how common antihypertensive agents, particularly calcium channel
blockers (CCBs) and β-blockers, effect pathophysiologic mechanisms of HFpEF. We propose a novel
mechanistic investigation of the role of dihydropyridine CCBs compared to β-blockers in targeting key
physiologic abnormalities in HFpEF.
HFpEF is characterized by unique physiologic abnormalities that may be differentially impacted by β-blockers
and CCBs. Excessive β-adrenergic stimulation may be a driver of reduced aerobic capacity in HFpEF, which
may respond favorably to β-blockade. However, in HFpEF, β-blockers may reduce cardiac output, particularly
during exercise, contributing to impaired cardiac output reserve and aerobic limitations. β-blockers may also
have effects on the pattern of ventricular contraction and arterial load, impacting diastolic function. Similarly,
CCBs may have beneficial effects related to vasodilation and reduction in late systolic load beyond their BP-
lowering effect. However, CCB-induced vasodilation at rest may limit the vasodilatory reserve. Our goal is to
assess the mechanisms by which CCBs and β-blockers (commonly used antihypertensive agents in clinical
practice), impact aerobic capacity and quality of life in HFpEF. We will compare the impact of a dihydropyridine
CCB (amlodipine besylate 5-10mg daily) vs. a β-blocker (metoprolol succinate 100-200mg daily) on arterial
function, chronotropic reserve, vasodilatory reserve, and LV function, among 50 subjects with HFpEF in a
randomized cross-over trial design. Participants will receive 4 weeks of each intervention, with a 1-week
washout period in-between. Our mechanism-driven approach will enhance our understanding of the
pathophysiology of HFpEF and characterize the physiologic potential of these common antihypertensive
agents to reduce progression and improve symptom management in this disease.

## Key facts

- **NIH application ID:** 10909150
- **Project number:** 5R01HL153646-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Jordana B. Cohen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $622,706
- **Award type:** 5
- **Project period:** 2020-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10909150

## Citation

> US National Institutes of Health, RePORTER application 10909150, Blockade of calcium channels and beta adrenergic receptors for physiologic abnormalities in heart failure with preserved ejection fraction (BLOCK HFpEF) (5R01HL153646-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10909150. Licensed CC0.

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