Long-Covid INOCA is an investigator-initiated, prospective, randomized, sham-controlled,
single center study intended to compare the benefits in angina symptom and Quality of
Life assessed by the Seattle Questionnaire of Angina (SAQ) between tailored medical
therapy guided by the results of the coronary functional testing (CFT) and the routine
standard of care in patient with LCS and new onset of chest pain. Secondary objective is
to investigate the prevalence and type of INOCA in LCS patients with chest pain. This
study will be conducted at Hospital Cliníco San Carlos, Madrid, Spain.

All patients with the history of SARS-CoV-2 infection, either with acute infection
confirmed by PCR or antigen testing, or with past infection demonstrated by serological
testing, with symptoms suggestive of LCS such as post exertional malaise, persistent
fatigue, difficulty concentrating or shortness of breath who present with typical angina
or angina equivalent chest pain starting after SARS-CoV2 infection will be enrolled in
this study.

After obtaining patient's informed consent. patients will be randomized by simple
randomization in a 1:1 ratio using a central online module to 1) tailored treatment
guided by the results of CFT (intervention) or 2) the routine standard of care treatment
(sham). All patients will undergo an invasive coronary angiogram as a first step.
Patients with severe epicardial coronary artery stenosis define by stenosis ≥ 90% by
angiogram will be excluded for further testing. Patients with intermediate coronary
artery stenosis will undergo a wire-based physiological assessment of epicardial
stenosis. If there is a significant epicardial coronary artery disease defined by
fractional flow reserve (FFR) ≤ 0.80 or non-hyperemic pressure ratio (NPHR) ≤ 0.89, the
patients will be excluded for further testing. In patients without significant epicardial
coronary artery disease, coronary functional testing which include coronary microvascular
dysfunction test and Acetylcholine test will be performed. Both tests will be performed
in a standard fashion according to the protocol from the guidelines. The results of the
CFT will be reported as follow: 1) normal coronary functional testing 2) vasomotor
disorder (including both epicardial and microvascular) 3) coronary microvascular
dysfunction (including both structural and functional) and 4) combined vasomotor disorder
and coronary microvascular dysfunction.

All patients will receive the medications for treatment of INOCA at an out-patient
clinic. In intervention group, patient and physician will receive the CFT's results and
medications will be prescribed according to patient's type of INOCA and follow with the
recommendations in the EAPCI Consensus Document on INOCA and ESC Guidelines. In sham
group, patient and physician will be blinded from the CFT's results for 3 months and
medications will be prescribed according to physician's decision during this period.
After 3 months, the CFT's result will be given to all patients and the treatment will
follow with the recommendations from the guideline. Angina symptom and Quality of life in
both groups will be assessed by the Seattle Questionnaire of Angina (SAQ), Duke Activity
Status Index (DASI) and Euro-Quality of life 5D (EQ-5D) at baseline and each follow up
which will occur at 3, 6 and 12 months.