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Mechanisms Behind Microvascular Dysfunction in INOCA

Not yet recruiting
Conditions
Ischaemia With Non Obstructed Coronary Arteries
Coronary Microvascular Dysfunction
Interventions
Diagnostic Test: [15O]H2O-PET Imaging
Registration Number
NCT06529861
Lead Sponsor
Bispebjerg Hospital
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.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
60
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).

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Control[15O]H2O-PET Imagingcontrols without angina
Ischemia and no obstructive coronary arteries[15O]H2O-PET Imagingpatients with angina and reduced myocardial blood flow reserve
Primary Outcome Measures
NameTimeMethod
Vascular function in response to acetylcholine stressBaseline only

Vascular conductance measured by ultrasound doppler during infusion of acetylcholine

Secondary Outcome Measures
NameTimeMethod
Vascular function in response to acetylcholine adenosine stressBaseline only

Vascular conductance measured by ultrasound doppler during infusion of Adenosine

Plasma Levels of Inflammatory MarkersBaseline only

Measured using Mesoscale/ELISA/O-Link platforms to evaluate the presence and levels of inflammatory markers

Plasma Levels of Markers Related to Vascular FunctionBaseline only

Assessed using Mesoscale/ELISA to quantify biomarkers associated with vascular function

Cardiac FunctionBaseline only

Changes in stroke volume using echocardiography during rest and exercise stress

Arterial Blood PressureBaseline only

Monitored with automated blood pressure measurements at rest and during exercise to assess overall cardiovascular health and response to physical activity.

Myocardial Blood flow reserveBaseline only

Determined by the clinical assessment of \[15O\]H2O-PET

Changes in isolated small artery reactivity assessed with myographyBaseline only

Analyzed using myograph to study the tone of smooth muscle cells

Plasma LipidsBaseline only

Conducted through clinical chemical analysis to measure levels of HDL, and triglycerides in the blood, providing insights into lipid profiles.

Plasma HbA1cBaseline only

Conducted through clinical chemical analysis to measure levels of HbA1c in the blood, providing insights into glucose metabolism.

Arterial ComplianceBaseline only

Determined by calculations made from intra-arterial pressure and arterial diameter measurements obtained via ultrasound Doppler to assess arterial compliance.

Skeletal Muscle Microvascular FunctionBaseline only

Evaluated by brachial artery ultrasound Doppler in response to exercise stress to measure blood flow responsiveness in skeletal muscles.

Trial Locations

Locations (1)

Frederiksberg Hospital, Dept. of Cardiology, Building 16, Y3, Nordre Fasanvej 57, Frederiksberg, Denmark, 2000

🇩🇰

Copenhagen, Denmark

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