The goal of this clinical trial is to learn if a cardiac rehabilitation program (CRP) improves functional capacity in adults with INOCA (ischemia with non obstructive coronary arteries). The main questions it aims to answer are:

• Does CRP improves maximal functional capacity (measured by VO2peak) in INOCA patients?
• Does CRP improve as well quality of life, adherence to Mediterranean diet, emotional state, functional independence angina episodes and sleep quality?

Researchers will compare CRP (treatment group) to standard recommendations (control group) to see if CRP works better for INOCA patients

Participants will:

Take part of CRP or standard recommendations for 3 months Visit the clinic in the beginning and in the end of the study for checkups and tests

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.

Inclusion Criteria:

• All men or women >18 years old with cath lab diagnosis of INOCA of 2 possible endotypes: vasoespasm or microvascular disease.
• All participants must have a mobile device/tablet/computer with internet access to connect to exercise and educational sessions
• 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.

Exclusion Criteria:

• 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

All IPD collected throughout the trial

Beginning 3 months and ending 1 year after the publication of results

Access to IPD and supporting information will be granted to qualified researchers, healthcare professionals, and regulatory authorities for scientific, clinical, or public health purposes. Requests will be reviewed by an independent data access committee to ensure compliance with ethical and legal requirements.

Available Data: De-identified IPD, study protocol, statistical analysis plan, informed consent form template, and study results summary.

Access Mechanism: Applicants must submit a research proposal, sign a data use agreement (DUA), obtain committee approval, and access data via a secure platform.

Ethical and Legal Compliance: Access will follow GDPR, HIPAA, and ethical guidelines, ensuring de-identification and restricted use for approved research purposes.

Data Availability: Data will be accessible for at least five years post-publication, with potential extensions.

Contact: For access requests, contact margacal1912@gmail.com