PROJECT SUMMARY/ABSTRACT
Heart failure (HF) affects more than 6 million adults in the U.S. alone, with increasing prevalence. Cardiovascular
congestion with resultant limitation in physical activity is the hallmark of chronic and decompensated HF. The current
HF physiologic model suggests that congestion is the result of volume retention and, therefore, therapies (such as
diuretics) have generally been targeted at volume overload. Yet therapeutic approaches to reduce congestion have
failed to show significant benefit on clinical outcomes, potentially due to an untargeted approach of decongestive
therapies. My preliminary work suggested a complimentary contribution of volume redistribution to the mechanism of
cardiac decompensation. I identified the splanchnic nerves as a potential therapeutic target and showed that short-
term interruption of the splanchnic nerve signaling could have favorable effects on cardiovascular hemodynamics
and symptoms.
My goal in seeking a Mentored Research Career Development Award is to acquire the necessary training and
experience to develop personalized treatment approaches to patients with HF and advance autonomic modulation
as a therapeutic intervention to treat cardiac congestion, improve functional status, and prevent HF decompensation.
As part of my proposal I will: (1) test the safety and efficacy of prolonged splanchnic nerve block in a randomized,
controlled, open-label study; and (2) define congestion phenotypes in HF using multi-level diagnostic testing. The
novel therapeutic approach could present a paradigm shift in the treatment of HF. Leveraging resources unique to
Duke University, the proposed aims will not only test this paradigm, but also help us understand which phenotype is
more likely to be caused by volume redistribution rather than volume overload. The mentorship team, led by Dr.
Adrian Hernandez, Vice Dean of Clinical Research and HF specialist, includes internationally-renowned experts in
the fields of HF, clinical trial design/operations (Dr. Manesh Patel), congestion testing (Dr. Michael Felker), exercise
physiology (Drs. William Kraus and Barry Borlaug), autonomic testing (Drs. Boortz-Marx and Benjamin Levine) and
quantitative training (Kevin Anstrom, PhD). Combined with formal didactics, they will provide the support needed to
achieve my training aims to develop skills in: (1) HF phenotyping including exercise physiology, congestion and
autonomic testing; (2) trial design and operations; (3) data reduction and analysis.
The results of the proposed scientific aims will help test the paradigm-shifting hypothesis of volume redistribution as
a driver of cardiovascular congestion and functional limitations and pave the way for splanchnic nerve blockade as a
novel therapeutic approach to HF. With the completion of the training aims, I will be uniquely-positioned as a clinical
HF specialist, trained in rigorous research methodology, to assess multiple critical components of HF physiology,
execute clinical trials, and test novel interventional therapies. The Career Development Grant proposal will provide
me the necessary skills to successfully pursue my goal of establishing an independent research program geared
towards personalizing treatments for patients with HF.