The prevalence of heart failure (HF) is increasing, and it is estimated that there will be 9.6 million U.S. adults who have HF by 2030. More than 50% of HF patients have a type of heart failure with preserved ejection fraction (HFpEF), also termed diastolic HF. The hallmark symptoms of HFpEF are lack of energy, fatigue, shortness of breath, exercise intolerance, and decreased quality of life. These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, patients with HFpEF suffer with severe lack of energy and other debilitating symptoms that affect their overall health-related quality of life. We have pilot data on patients with HFpEF showing that two supplements (ubiquinol and D-ribose) added to their usual HF care enhanced their myocardial energetics and diastolic function resulting in decreased symptom burden. Both ubiquinol (reduced form of coenzyme Q10) and D-ribose play a vital role in mitochondrial adenosine triphosphate (ATP) production. Thus, we propose a biobehavioral symptom science study using these two supplements (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF. Using a randomized, double-blind, placebo-controlled study, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. There are two aims.
AIM 1 : To determine the effects of oral ubiquinol, D-ribose, or a combination of the two administered over 12 weeks on symptoms accompanying low bioenergetics in patients with HFpEF. The measures used to assess patients' perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The KCCQ includes five domains such as physical limitations, symptoms, self- efficacy, quality of life, and social interactions.
AIM 2 : To determine the effects of oral ubiquinol, D-ribose, or a combination of the two over 12 weeks on biological measures in patients with HFpEF. The 6-minute walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics). These measures will determine if patients with HFpEF experience improved functional and clinical outcomes. Measures will be obtained at baseline, 6 weeks, and 12 weeks. The projected patient outcomes are improved health status, enhanced energy, increased 6-minute walking distance, improved cardiac performance, lower B-type natriuretic peptide, and increased ATP production. Improved clinical outcomes will enhance the patients' self- care activities of daily living, leading to better quality of life.

Public Health Relevance

Heart failure with preserved ejection fraction (HFpEF) is a type of heart failure with biological (e.g., heart stiffness, diminished cell energy) and behavioral symptoms (e.g., lack of energy, shortness of breath, leg swelling). It is a leading cause of morbidity and mortality in the U.S. Our pilot data in patients with HFpEF who used ubiquinol (type of CoQ10) and/or D-ribose showed reduction in their symptoms and significant improvement in heart performance. The proposed study will provide essential information to determine if these supplements added to the usual care for patients with HFpEF would have decreased symptoms, better heart function, and improved quality of life.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Nursing and Related Clinical Sciences Study Section (NRCS)
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Romashkan, Sergei
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University of Kansas
Schools of Nursing
Kansas City
United States
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Pierce, Janet D; Mahoney, Diane E; Hiebert, John B et al. (2018) Study protocol, randomized controlled trial: reducing symptom burden in patients with heart failure with preserved ejection fraction using ubiquinol and/or D-ribose. BMC Cardiovasc Disord 18:57
Mahoney, Diane E; Hiebert, John B; Thimmesch, Amanda et al. (2018) Understanding D-Ribose and Mitochondrial Function. Adv Biosci Clin Med 6:1-5