Determinants of Cardiorespiratory Fitness and Effects of High Intensity Interval Training (HIIT) in Patients With Angina and No Obstructive Coronary Artery Disease (ANOCA)

The overall research plan is for 25 subjects with angina and no obstructive coronary artery disease (ANOCA) on invasive or coronary CT angiography (ANOCA Study Population) to undergo cardiopulmonary exercise testing (CPET) to assess exercise workload and hemodynamic variables and health-related quality of life (HRQOL) measurement at baseline, followed by repeat testing after high-intensity interval exercise training for 4 weeks. The investigators will examine the diagnostic role of exercise by determining the relationship between exercise fitness and assessing the degree of cardiac, ventilatory, and muscle impairment on CPET.

Anginal burden and related functional status will be assessed via the Seattle Anginal Questionnaire. Overall functional status will be assessed through the Short form (SF36) and MacNew forms, levels of cardiac anxiety through the Cardiac Anxiety Questionnaire (CAQ), and effects on work absenteeism and presenteeism through the Work Limitations Questionnaire (WLQ). Baseline exercise status will be documented through the Duke Activity Status Index form.

The investigators will identify cardiorespiratory fitness peak oxygen consumption (VO2peak) and CPET phenotype with ANOCA. The investigators hypothesize that patients with ANOCA will have reduced VO2 peak and heterogeneous CPET phenotypes with substantial and varying contributions of cardiac, ventilatory, and muscle impairment. Phenotyping of determinants of exercise intolerance will be carried out using the following CPET parameters: cardiac-VO2peak, non-invasive cardiac output with CO2 rebreathing, and O2pulse; ventilatory via VE/VO2and oxygen uptake efficiency slope (OUES); muscle by VE/VCO2 slope, a-vO2 difference, and quadriceps muscle strength on isokinetic dynamometry. The Investigators predict that cardiac impairment will be the most frequent CPET phenotype in ANOCA, and this group will have poor exercise fitness.

The investigators will perform a 4-week high-intensity interval exercise training in 25 patients with ANOCA. The investigators will examine the feasibility of a remote exercise program with ramp exercise thresholds. The investigators predict that exercise program session adherence will be >80% based on preliminary data. The investigators will assess the effect of HIIT on CPET phenotype, improvement in VO2peak in patients with varying CPET phenotypes, model entropy, and HRQOL overall score and specific functional domains. The investigators predict that VO2peak will significantly improve with HIIT.

The exercise protocol for subjects will entail one initial supervised exercise session. All subsequent exercises will be done remotely. Each heart rate monitor will be programmed with heart rate zones that are 85-90% of that subject's angina threshold on the CPET. Subjects will be instructed to start with one 1-minute exercise and one 1-minute rest. The protocol will increase the length of exercise with the goal of getting up to four 4-minute sessions of exercise on three non-consecutive days of the week.