The Relationship of Exercise Associated Cardiac Reserve on Peak Oxygen Consumption and Frailty Measures in Individuals Undergoing Allogeneic Hematopoietic Stem Cell Transplant.

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PROJECT SUMMARY This K23 project will prepare the Principal Investigator, Justin M. Canada, PhD, to develop as an independent clinical/translational researcher who is expert in a novel form of cardiopulmonary exercise stress measurement – cardiovascular magnetic resonance imaging (MRI) – to identify factors that reduce peak oxygen consumption (VO2) in patients with heart failure. Peak VO2 reflects peak exercise capacity, a prime determinant of outcomes among patients with cardiovascular disease (CVD). This noninvasive methodology does not require intravenous contrast or ionizing radiation, eliminating possible side effects among patients in poor health. It also accurately measures exercise-associated cardiac output—a fundamental contributor to overall exercise capacity—that can be targeted with therapeutic interventions to improve overall peak exercise capacity. This project is a collaborative multi-disciplinary effort among oncologists, exercise physiologists, biomedical engineers, and cardiovascular experts to address an important issue in the emerging field of cardio-oncology. The proposal focuses on patients receiving allogeneic hematopoietic stem cell transplantation (HCT) for hematologic malignancies. Treatment-associated reductions in peak VO2 can exclude candidates from life- saving HCT. Among survivors of hematologic malignancies, reduced peak VO2 is associated with impaired quality of life and elevated risk of death not related to relapse. At present, there is no reliable method to identify those at risk for these serious adverse events. In addition to a strong, supportive environment that includes international experts, the largest HCT program in Virginia, and state-of-the-art equipment co-located within the Cancer Center that serves the HCT community, the proposal is buttressed by highly supportive preliminary data and a robust career development plan for Dr. Canada. This plan provides mentored training in the translational fundamentals of MRI theory: conduct, interpretation, and MRI application in cardiovascular and cardio-oncology clinical management. This includes expertise in the technical aspects, analysis, interpretation, and utilization of an innovative exercise stress-associated cardiovascular MRI technique to discern the mechanism of reduced exercise capacity in other heart failure syndromes. This patient-oriented mentored research training plan incorporates a highly innovative technique and an excellent training environment to develop and test a methodology that identifies the causes of reductions in peak exercise capacity, a primary determinant of HCT outcomes. The outstanding mentor team will guide the Candidate’s progress in professional milestones (publications and presentations) and oversee his continued exposure to responsible conduct of research training. At completion of this K23, Dr. Canada will be well- qualified to contribute meaningfully to an emerging field of growing research interest.