RECOVER with INOCA: a Randomized, Prospective Study of a Cardiac Rehabilitation Program in Patients with Ischemia with Nonobstructive Coronary Artery Disease (INOCA)

A prospective, single-centre, randomized study with patients diagnosed with INOCA to assess their participation in a 3-month telehealth-based holistic cardiac rehabilitation program (CRP). Exclusion criteria were based on contraindications for participating in the telehealth CRP: alarm signs in the stress test (ventricular arrhythmias, hypotensive response, ST segment changes, or symptoms of ischemia), left ventricular ejection fraction (LVEF) <40%, or presence of pacemakers/defibrillators. Additionally, patients without a mobile device/tablet/computer with internet access to connect to exercise and educational sessions were excluded. Finally, participants should be stable in terms of angina episodes, defined as the absence of hospitalizations or decompensations in the number of angina episodes, as well as no changes in antianginal medications for 3 months prior to inclusion.

The primary endpoint is the improvement in functional capacity, objectively measured by the change in peak oxygen consumption (VO2peak) obtained from cardiopulmonary exercise testing (CPET) after 3 months of CRP (treatment group), compared to standard recommendations (control group). Secondary endpoints are CRP impact on quality of life, adherence to Mediterranean diet, emotional state, functional independence, angina episodes and sleep quality. The investigators selected pure VSA and pure MCA endotypes for the inclusion, to avoid confusion factors and to see if there were different results between both endotypes. A sample of 24 patients was selected to detect a 4.5 ml/kg/min difference in VO2peak.

The study scheme is as follows:

1. Recruitment: INOCA patients (confirmed diagnosis with microcirculation and provocation testing) are referred from ischemic heart disease consultations.
2. Initial Assessment Visit:

• Part 1: Cardiologist and hemodynamic nurse explain the project, and if the patient agrees to participate, randomization (CRP yes or no) occur, and informed consent is signed. Blood samples are taken for initial assessment (basic profile, haemostasis, lipid profile, and HbA1c). Additionally, scales for quality of life (EuroQol), anxiety and depression (HADS), Mediterranean diet (PREDIMED), weekly exercise volume (IPAQ), functional (Barthel), and angina (SAQ-7) assessments are completed.
• Part 2: Assessment in the cardiac rehabilitation clinic and initial CPET (cardiopulmonary stress test) testing for all patients. If the patient belongs to the CRP group, an individualized exercise prescription is made for the physiotherapist. If not, general exercise recommendations are provided. In both cases, a final CPET visit is scheduled at 3 months.

3. Cardiac Rehabilitation Program (3-month duration, for the intervention group): 2 individualized exercise sessions per week (via Teams platform) with the physiotherapist, 1 educational session per week via Teams with nursing, and 1 educational session per week via Teams with psychology.
4. Final Visit in Cardiac Rehabilitation: Scales wee reassessed, CPET is conducted, and a final medical assessment is performed. A final blood test and nursing assessment is also conducted, including an ad hoc patient experience survey regarding the program. A final medical report with their evolution and recommendations for follow up is given to all patients.