This proposal represents a joint effort combining the vast infrastructure, extensive clinical and research experience, as well as large patient volumes in heart failure at the Cleveland Clinic, together with the clinical trial expertise and diverse patient populations at University Hospitals and MetroHealth Medical Center to establish the Cleveland Regional Clinical Center (RCC). Led by Drs. W. H. Wilson Tang and Randall C. Starting and joined by Drs. James Fang and Mark Dunlap as co-investigators, and taking advantage of the Cleveland Clinical and Translational Sciences Collaborative (CTSC) that recently integrated the research infrastructure our three institutions, our goal is to participate in the Heart Failure Clinical Research Network to test new hypotheses and therapies to advance the management of heart failure. In particular, we hope to expand our longstanding academic interest in developing strategies to alleviate cardio-renal compromise in congestive heart failure. Our proposed project serves as a mechanistic study to discern the possible role of renal sympathetic nerves in mediating cardiac and/or renal complications of the cardio-renal syndrome. Utilizing a novel, catheter-based renal sympathetic denervation (RSD) technique currently under investigation for treatment of refractory hypertension (Symplicity Catheter System), we test the hypothesis that in patients with hypertensive heart failure recently admitted for congestive heart failure that RSD may provide incremental improvement in neurohormonal profile, improve cardio-renal function, and facilitate symptomatic relief over usual care. Our consortium provides a unique opportunity to contribute to the overall Network with clinical trials expertise and leadership in heart failure to fulfill the scientific requirements, and the diverse and broad regional patient populations across a wide range of practice settings with proven abilities to recruit and fulfill the performance requirements, and to test a novel treatment approach to tackle one of the most challenging aspects of contemporary heart failure.

Public Health Relevance

The incidence of heart failure continues to increase in large due to the expansion of the aging population and therapeutic advances in the management of acute cardiovascular diseases. The presence of cardio-renal dysfunction constitutes a major impediment to adequate management of heart failure, and further understanding and novel strategies to relieve cardio-renal compromise is a priority to improve outcomes.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Cooperative Clinical Research--Cooperative Agreements (U10)
Project #
5U10HL110336-02
Application #
8403727
Study Section
Special Emphasis Panel (ZHL1-CSR-K (O2))
Program Officer
Shah, Monica R
Project Start
2012-01-01
Project End
2018-12-31
Budget Start
2013-01-01
Budget End
2013-12-31
Support Year
2
Fiscal Year
2013
Total Cost
$361,100
Indirect Cost
$131,100
Name
Cleveland Clinic Lerner
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
135781701
City
Cleveland
State
OH
Country
United States
Zip Code
44195
Vader, Justin M; LaRue, Shane J; Stevens, Susanna R et al. (2016) Timing and Causes of Readmission After Acute Heart Failure Hospitalization-Insights From the Heart Failure Network Trials. J Card Fail 22:875-883
AbouEzzeddine, Omar F; Lala, Anuradha; Khazanie, Prateeti P et al. (2016) Evaluation of a provocative dyspnea severity score in acute heart failure. Am Heart J 172:34-41
Wan, Siu-Hin; Stevens, Susanna R; Borlaug, Barry A et al. (2016) Differential Response to Low-Dose Dopamine or Low-Dose Nesiritide in Acute Heart Failure With Reduced or Preserved Ejection Fraction: Results From the ROSE AHF Trial (Renal Optimization Strategies Evaluation in Acute Heart Failure). Circ Heart Fail 9:
Grodin, Justin L; Lala, Anuradha; Stevens, Susanna R et al. (2016) Clinical Implications of Serum Albumin Levels in Acute Heart Failure: Insights From DOSE-AHF and ROSE-AHF. J Card Fail 22:884-890
Grodin, Justin L; Stevens, Susanna R; de Las Fuentes, Lisa et al. (2016) Intensification of Medication Therapy for Cardiorenal Syndrome in Acute Decompensated Heart Failure. J Card Fail 22:26-32
Margulies, Kenneth B; Hernandez, Adrian F; Redfield, Margaret M et al. (2016) Effects of Liraglutide on Clinical Stability Among Patients With Advanced Heart Failure and Reduced Ejection Fraction: A Randomized Clinical Trial. JAMA 316:500-8
AbouEzzeddine, Omar F; Wong, Yee Weng; Mentz, Robert J et al. (2016) Evaluation of Novel Metrics of Symptom Relief in Acute Heart Failure: The Worst Symptom Score. J Card Fail 22:853-858
Hussain, Imad; Mohammed, Selma F; Forfia, Paul R et al. (2016) Impaired Right Ventricular-Pulmonary Arterial Coupling and Effect of Sildenafil in Heart Failure With Preserved Ejection Fraction: An Ancillary Analysis From the Phosphodiesterase-5 Inhibition to Improve Clinical Status And Exercise Capacity in Diastolic Circ Heart Fail 9:e002729
Redfield, Margaret M; Anstrom, Kevin J; Levine, James A et al. (2015) Isosorbide Mononitrate in Heart Failure with Preserved Ejection Fraction. N Engl J Med 373:2314-24
Givertz, Michael M; Anstrom, Kevin J; Redfield, Margaret M et al. (2015) Effects of Xanthine Oxidase Inhibition in Hyperuricemic Heart Failure Patients: The Xanthine Oxidase Inhibition for Hyperuricemic Heart Failure Patients (EXACT-HF) Study. Circulation 131:1763-71

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