Coronary Microvascular Dysfunction, Ischaemia With Non Obstructed Coronary Arteries
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DIAGNOSTIC_TEST[15O]H2O-PET Imaging
This imaging technique will be used to measure myocardial blood flow (MBF) and myocardial blood flow reserve (MBFR) in patients. The PET-CT scan involves the use of the radioactive tracer \[15O\]H2O to visualize blood flow in the heart, providing crucial data on coronary microvascular function.
Sponsors
University of Copenhagen
Bispebjerg Hospital
Study design
Observational model
COHORT
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
Yes
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Vascular function in response to acetylcholine stress | Baseline only | Vascular conductance measured by ultrasound doppler during infusion of acetylcholine |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Vascular function in response to acetylcholine adenosine stress | Baseline only | Vascular conductance measured by ultrasound doppler during infusion of Adenosine |
| Myocardial Blood flow reserve | Baseline only | Determined by the clinical assessment of \[15O\]H2O-PET |
| Skeletal Muscle Microvascular Function | Baseline only | Evaluated by brachial artery ultrasound Doppler in response to exercise stress to measure blood flow responsiveness in skeletal muscles. |
| Changes in isolated small artery reactivity assessed with myography | Baseline only | Analyzed using myograph to study the tone of smooth muscle cells |
| Arterial Compliance | Baseline only | Determined by calculations made from intra-arterial pressure and arterial diameter measurements obtained via ultrasound Doppler to assess arterial compliance. |
| Plasma Lipids | Baseline only | Conducted through clinical chemical analysis to measure levels of HDL, and triglycerides in the blood, providing insights into lipid profiles. |
| Arterial Blood Pressure | Baseline only | Monitored with automated blood pressure measurements at rest and during exercise to assess overall cardiovascular health and response to physical activity. |
| Cardiac Function | Baseline only | Changes in stroke volume using echocardiography during rest and exercise stress |
| Plasma HbA1c | Baseline only | Conducted through clinical chemical analysis to measure levels of HbA1c in the blood, providing insights into glucose metabolism. |
| Plasma Levels of Markers Related to Vascular Function | Baseline only | Assessed using Mesoscale/ELISA to quantify biomarkers associated with vascular function |
| Plasma Levels of Inflammatory Markers | Baseline only | Measured using Mesoscale/ELISA/O-Link platforms to evaluate the presence and levels of inflammatory markers |
Other
| Measure | Time frame | Description |
|---|---|---|
| Tone of smooth muscle cells | Baseline only | Changes in isolated small artery reactivity assessed with myography |
| Proteomic and transcriptomic analyses | Baseline only | Changes in gene and protein expressions patterns in small arteries |
Countries
Denmark
Contacts
Primary ContactEva Prescott, MD, DMSc
Backup ContactMads Fischer, Ph.D.
Outcome results
None listed