SPUR 2019: Peripheral Limitations to Maximal Oxygen Uptake in Patients with Heart Failure and Preserved Ejection Fraction

Background

Heart failure with preserved ejection fraction (HFpEF) accounts for greater than 50% of all heart failure cases, and the prevalence relative to heart failure with reduced ejection fraction (HFrEF) continues to rise at a rate of 1% per year, with a 5-year survival rate as low as 50%. The pathophysiological differences between HFpEF and HFrEF, coupled with unsuccessful therapeutic strategies, highlight the need for improved understanding of HFpEF. The pathophysiological differences between HFpEF and heart failure with reduced ejection fraction (HFrEF), coupled with unsuccessful therapeutic strategies, highlight the need for improved understanding of HFpEF.

The defining symptom of HFpEF is marked exercise intolerance that greatly limits physical activity and quality of life. In patients with HFpEF, maximal oxygen uptake (VO2max), a primary determinant of prognosis and quality of life, has best quantified the severity of exercise intolerance. The peripheral limitations to VO2max will be determined in patients with HFpEF and controls by measuring leg maximal O2 delivery, O2 consumption, and mitochondrial oxidative capacity (Aim 1). Next, the identification of an O2-supply or O2-demand limitation will be validated by measuring the hyperoxia-induced changes in leg maximal O2 delivery and O2 consumption in patients with HFpEF and controls (Aim 2). Finally, the effect of knee-extensor training on the peripheral limitations to VO2max will be assessed by measuring the training-induced changes in leg maximal O2 delivery, O2 consumption, and mitochondrial oxidative capacity in patients with HFpEF and controls (Aim 3).

The stipend for this SPUR project is funded by an American Heart Association grant awarded to Dr. Stavros Drakos, MD, PhD.

Student Role

The student will assist with patient visits to the laboratory, thus, getting first hand training in data collection and analysis. Specifically, the student will help calibrate devices and use the laboratory techniques for this study. This includes, but not limited to: Finapress, a non-invasive continuous blood pressure monitor; BioPak, data acquisition hardware; Single-leg ergometer; Blood gas analyzer. The student will observe leg catheter placements by our anesthesiologists, Doppler ultrasound testing of femoral blood flow and venous and arterial blood draws. The student will develop presentation skills by attending and presenting in the weekly UVRL Research in Progress and Journal Club meetings.

Student Learning Outcomes & Benefits

Involvement in the proposed research project will provide the student with the required training to further develop their research capabilities in the field of applied clinical cardiovascular physiology and help their personal development toward becoming inquisitive and hypothesis driven scientists. The UVRL has had considerable success in assisting trainees to achieve their career goals and expect this to again be the case with the SPUR program.

Russell Richardson
Professor

Internal Medicine
School of Medicine

The student will not only work with their assigned mentor, but will work closely with numerous Graduate Students and Postdoctoral Fellows with a defined individual to be responsible for their final research project/poster presentation. The following 3 components of this experience will help develop the student’s research capabilities:

  1. Scientific training, the student will be immersed in the above projects, or similar, and will, thus, get first hand training in data collection and analysis as it relates to applied cardiovascular and metabolic research.
  2. Presentation skills, the student will attend and partake in the weekly UVRL Research in Progress and Journal Club meetings which will foster this aim.
  3. Personal development, the student will be encouraged and guided in terms of critical thinking and experience increasing personal responsibility. This will be achieved by the iterative approach of giving additional opportunities to the student during the training period.