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Evaluating cardiac neural control in atrial fibrillation

Award Number: K08HL179399
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP
PERIOD OF PERFORMANCE START DATE: 07/15/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2031

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Evaluating cardiac neural control in atrial fibrillation - Project Summary/Abstract Atrial fibrillation (AF) is the most common heart rhythm disorder and is characterized by abnormal electrical conduction that manifests as uncoordinated atrial contraction. The arrhythmia increases risk of stroke and morality and is associated with significant healthcare costs. Current pharmacologic and ablation therapies have limited effectiveness, as many patients experience recurrences of AF. As the cardiac autonomic nervous system plays a critical role in cardiac physiology and pathophysiology, interventions in the cardiac neuraxis for the treatment of AF are an area of active investigation. Recent clinical trials evaluating ablation of ganglionated plexuses (GPs), clusters of neurons of the intrinsic cardiac nervous system that are embedded in epicardial fat pads, have shown no benefit in reducing arrhythmia recurrence as well as adverse effects necessitating pacemaker implantation. The central hypothesis of the proposed studies is that a subset of GPs may serve as targets for AF treatment while limiting off-target effects. In human hearts rejected for transplantation and donated to research, a retrograde neural tracer will be injected into the pulmonary veins and posterior wall of the left atrium, where AF is typically triggered and maintained. The neurons housed in GPs that supply this left atrial myocardium will be identified using confocal microscopy. Neurons in the GPs will also undergo an unbiased assessment using single-nucleus RNA sequencing to develop a compendium of neural subpopulations found across the intrinsic cardiac nervous system. Functional neuroanatomical studies will be performed by reanimating donated human hearts and performing pharmacologic and electrical stimulation followed by ablation of GPs coupled with an assessment of AF inducibility and off-target effects. Lastly, to understand the long-term consequences of GP ablation, a chronic porcine AF model will be developed, and effects on autonomic remodeling from catheter ablation of AF, which is the standard of care, will be compared to GP ablation. The information gained from the proposed studies will elucidate the composition of the intrinsic cardiac nervous system and how that system is involved in the pathophysiology of AF and may be intervened upon by catheter-based approaches. This research has the potential to result in refinement of current approaches and identification of novel therapeutics targets.


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 = $169,776 )
2026	2026	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Cardiovascular Diseases Research	000	1	7/10/2026	NEW	$169,776
														Subtotal = $169,776

Grand Total All Awards = $169,776

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Evaluating cardiac neural control in atrial fibrillation

Award Number: K08HL179399

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: TRAINING/TRAINEESHIP

PERIOD OF PERFORMANCE START DATE: 07/15/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2031

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