# Central Apnea in Heart Failure: Physiological Mechanisms to Inform Treatment

> **NIH VA I01** · JOHN D DINGELL VA MEDICAL CENTER · 2026 · —

## Abstract

Our objective is to test mechanistic pathways to inform future clinical studies investigating the potential treatment
of central sleep apnea (CSA) in veterans with heart failure and reduced ejection fraction (HF). The long-term
goal is to transform the care of veterans living with these two conditions. We will test two key determinants of
recurrent CSA in veterans with HF: augmented peripheral chemoreceptor activity and respiratory arousals.
Specifically, the project will utilize a novel PAP plus approach, combining PAP therapy to alleviate upper airway
obstruction with a specific intervention to target the mechanistic underpinnings of CSA. Our experiments will
capitalize on the plasticity of the CO2 reserve as the gateway to the resolution of CSA. We will suppress arousals
or dampen augmented PCR activity while maintaining upper airway patency with PAP. The long-term goal is to
inform future multi-modality intervention studies. To this end, the following Specific Aims will be addressed in
veterans with HF and CSA. Specific Aim 1: To determine the effect of decreasing respiratory arousals on the
propensity to CSA. Hypothesis 1: Four weeks of combined PAP and trazodone therapy will be superior to PAP
alone in elevating the arousal threshold, widening the CO2 reserve (primary outcome), and decreasing CSA
indices. Specific Aim 2: To determine the effect of decreased peripheral chemoreceptor sensitivity on the
propensity to CSA. Hypothesis 2: Four weeks of combined PAP and supplemental O2 (targeting peripheral
chemoreceptor sensitivity) will be superior to PAP alone in widening the CO2 reserve (primary outcome),
reducing controller gain, and decreasing CSA indices. The proposed studies are innovative, testing mechanistic
“PAP Plus” approach targeting underlying causes of CSA and alleviating upper airway obstruction with PAP.
These studies will inform future clinical trials to transform central apnea care in patients with heart failure.

## Key facts

- **NIH application ID:** 11299757
- **Project number:** 2I01RD001576-07A1
- **Recipient organization:** JOHN D DINGELL VA MEDICAL CENTER
- **Principal Investigator:** M.Safwan  Badr
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2026
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2026-04-01T00:00:00 → 2030-03-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11299757

## Citation

> US National Institutes of Health, RePORTER application 11299757, Central Apnea in Heart Failure: Physiological Mechanisms to Inform Treatment (2I01RD001576-07A1). Retrieved via AI Analytics 2026-05-18 from https://api.ai-analytics.org/grant/nih/11299757. Licensed CC0.

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