The purpose of the study is to identify the causes of chest pain in patients experiencing chest pain with no signs of narrowing in the coronary arteries of the heart.

A significant number of patients with ischemic heart disease do not exhibit coronary obstruction, leading to their symptoms being attributed to coronary microvascular dysfunction, a condition known as ischemia with no obstructive coronary artery disease (INOCA). Despite a considerable patient population affected by INOCA, the specific mechanisms underlying this microvascular dysfunction are not fully understood, often resulting in a lack of targeted treatment. There is evidence to suggest that exercise capacity is linked to coronary microvascular function, an area yet to be explored.

This study aims to identify mechanisms underlying Coronary microvascular dysfunction (CMD) in angina and to assess whether exercise training can improve the condition. In study part I 30 patients with impaired coronary microvascular function and 30 asymptomatic controls will be studied to identify vascular and related molecular mechanisms underlying INOCA by investigating microvascular function in the heart and in cutaneous tissue, skeletal muscle, and adipose tissue.

Inclusion Criteria:

Only for angina patients: Have CMD, defined as myocardial bloodflow re-serve (MBFR) < 2.5 or hyperemic myocardial blood flow (hMBF) < 2.3ml/g/min

Exclusion Criteria:

• Females of childbearing potential (defined as a premeno-pausal female capable of becoming pregnant). The female patient must either be postmenopausal, defined as amen-orrhea for at least 1 year, or surgically sterile
• Heart failure, defined as left ventricular ejection fraction of less than 40%
• Uncontrolled hypertension defined as blood pressure above target 140/90 for all
• Co-morbidity resulting in <1 year expected survival
• Considered by the investigator, for any reason, to be an unsuitable candidate for the study.
• Unable or unwilling to exercise, e.g. due to arthritis or injury*
• Already are regularly physically active and/or have a maximal oxygen uptake >45 ml/kg/min
• The subject has a known allergy to either: norepinephrine, adenosine, ketorolac, and or ascorbic acid (vitamin C).

Ischemia with no obstruction of coronary arteries (INOCA) is estimated to affect >150.000 Danes and the majority are females. These patients have a shorter life expectancy than age matched controls and a higher incidence of major cardiovascular events (1,2).

INOCA is caused by microvascular dysfunction. When there is dysfunction in the microvascu-lature, the blood flow within the coronary vessels fails to increase adequately to meet the de-mand, resulting in ischemia and pain (angina).