CMD, Coronary Microvascular Disease
Conditions
Brief summary
The purpose of the study is to identify causes of chest pain in patients experiencing chest pain with no signs of narrowing of the coronary arteries of the heart, and to investigate whether physical exercise can improve coronary microvascular function. Hypotheses: The first hypothesis is that in INOCA, with reduced function of microvasculature of the heart, this reduced function also occurs in other organs of the body. The second hypothesis is that regular physical activity (aerobic exercise training) can improve coronary microvascular function, reduce symptoms, and that there is a parallel improvement in vascular function in other organs of the body.
Detailed description
A significant number of patients suspected of chronic coronary syndrome do not have coronary artery obstruction and in a large proportion of these, their symptoms are attributed to coronary microvascular dysfunction (CMD), a condition known as ischemia with no obstructive coronary artery disease (INOCA). Despite a considerable patient population affected by INOCA, the specific mechanisms underlying CMD 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, positing that exercise training could potentially reverse microvascular dysfunction and address its mechanistic origins, a hypothesis yet to be explored. This study aims to identify mechanisms underlying CMD in angina and to assess whether exercise training can improve the condition. The current study is a randomized controlled trial testing the effect of exercise training in patients with CMD. 100 patients will be randomized 1:1 to exercise training or control. The primary outcome is coronary microvascular function, secondary outcomes include symptoms and microvascular function in cutaneous tissue, skeletal muscle, and adipose tissue.
Interventions
OTHERExercise training
The training sessions are consist of cycling and as follows: a 10 min warm-up at a light intensity, 20-35 min of cycling exercise in intervals at varying intensities from light (\ 60% of max heart rate) to more intensive (80-90% of max heart rate) and ending with 5 min of warm-down at a light intensity. The training intensity will be progressive during the course of the intervention period. The cycling training sessions are supervised . Home training is allowed up to once a week if participants are able to adhere to the prescribed intensity levels. Training sessions are closely monitored to ensure effectiveness and safety. This includes heart rate monitoring, perceived exertion assessment.
Sponsors
University of Copenhagen
Bispebjerg Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized controlled trial in which 100 angina patients with reduced flow reserve (INOCA patients) are randomized 1:1 to either exercise training or control (no exer-cise training).
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Coronary microvascular dysfunction, defined as myocardial bloodflow reserve (MBFR) \< 2.5 or hyperemic myocar-dial blood flow (hMBF)\<2.3 ml/g/min using \[15O\]H2O-PET * No obstructive coronary artery disease
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 un-suitable candidate for the study. * Unable or unwilling to exercise, e.g. due to arthritis or in-jury\* * Already are regularly physically active and/or have a maxi-mal oxygen uptake \>45 ml/kg/min
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Myocardial Blood Flow Reserve (MBFR) | From baseline and after 3 months | Change in MBFR assessed by \[15O\]H2O-PET-scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in symptom burden assessed by Seattle Angina Questionnaire | From baseline and after 3 months | Seattle angina questionnaire/selfreported (scale range 0-100, 0=poor and 100=excellent health status) |
| Change in exercise capacity | From baseline and after 3 months | Oxygen uptake during exhaustive exercise |
| Change in global rest perfusion in patients with angina symptoms and CMD | From baseline and after 3 months | Change in Myocardial Blood Flow assessed by \[15O\]H2O-PET-scan |
| Change in global stress perfusion in patients with angina symptoms and CMD | From baseline and after 3 months | Change in hyperemic Myocardial Blood Flow assessed by \[15O\]H2O-PET-scan |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in Plasma Levels of Inflammatory Markers | From baseline and after 3 months | Measured using Mesoscale/ELISA/O-Link platforms to evaluate the presence and levels of inflammatory markers, indicating systemic inflammation. |
| Vascular Function Adaptations | From baseline and after 3 months | Changes in Arterial compliance (C = ΔV/ ΔP) calculated from intraarterial pressure ΔP and arterial diameter (ΔD) measured by ultrasound Doppler |
| Proteomic and transcriptomic analyses | From baseline and after 3 months | Changes in gene and protein expressions patterns in small arteries |
| Changes in skin microvascular function | From baseline and after 3 months | Hand microcirculatory blood flow assessed by Laser Speckle Contrast Imaging |
| Change in plasma levels of markers related to vascular function | From baseline and after 3 months | Plasma levels of markers related to vascular function assessed by Mesoscale/ELISA |
| Changes in Arterial Blood Pressure | From baseline and after 3 months | Assessed by automated blood pressure at rest |
| Change in plasma Lipids | From baseline and after 3 months | Conducted through clinical chemical analysis to measure levels of HDL, and triglycerides in the blood, providing insights into lipid profiles. |
Countries
Denmark
Contacts
Primary ContactEva Prescott, MD, DMSc
Backup ContactMads Fischer, MSc
Outcome results
None listed