To investigate whether MBV is reduced in patients with NOCAD and signs and symptoms of ischemia, relative to healthy controls. The specific aims are 1) to investigate if MBV is reduced in NOCAD patients at baseline, 2) to investigate if MBV is…
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Source
Brief title
Condition
- Coronary artery disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the statistical difference in MBV between NOCAD
patients and healthy controls. We compare MBV between groups at baseline,
during hyperinsulinemia and during increased cardiac contraction.
MBV is measured using MCE. Hyperinsulinemia is induced by a two hour HE-clamp
and cardiac stress with increased contraction is induced by the infusion of
dobutamine.
Secondary outcome
The insulin-mediated capillary recruitment (*MBV) is the difference in MBV at
baseline and after HE-clamp. Insulin-resistance is calculated using the M-value
of the last half hour of HE-clamp.
1. MBV, MBF, *MBV, baseline characteristics, cardiovascular risk factors,
questionnaire results, blood parameters and measurement indexes compared
between males and females from the patient and control group.
2. Differences in MBV and MBF between baseline and after HE-clamp of the
patient and control group and differences in MBV and MBF between baseline and
after dobutamine stress of the patient and control group.
3. Baseline characteristics, cardiovascular risk factors, questionnaire results
and measurement indexes compared between the patient and control group.
4. MBV, MBF and *MBV compared between insulin resistant subjects and
non-insulin resistant subjects.
5. Correlation between MBV (+other related variables) measured with MCE and MBV
measured with CMR.
6. Protein expression and phosphorylation of microvascular endothelial cells
compared between the patient and control group.
Background summary
About 21-46% of patients (i.e. 65% women and 35% men) with signs and symptoms
of ischemic heart disease have nonobstructive coronary artery disease (NOCAD).
Patients with NOCAD are at increased risk of major adverse cardiac events and
have worse prognosis compared to healthy people. The pathophysiology behind
NOCAD still remains unresolved, but includes coronary microvascular
dysfunction, spasm and impaired vascular effects of insulin. Myocardial blood
flow (MBF) and myocardial blood volume (MBV) are important parameters of the
coronary microcirculation. The coronary flow reserve (CFR) with infusion of
adenosine is currently used to assess coronary microvascular dysfunction,
although this technique might not be sensitive enough to detect coronary
microvascular dysfunction because no evaluation of MBV is possible. Studies
have shown that adenosine infusion increases MBF without an increase in MBV,
but that increased myocardial oxygen consumption or hyperinsulinemia increases
both MBF and MBV. Therefore, we hypothesize that dysregulation of the MBV
contributes to coronary microvascular dysfunction in NOCAD patients with signs
and symptoms of ischemic heart disease.
Study objective
To investigate whether MBV is reduced in patients with NOCAD and signs and
symptoms of ischemia, relative to healthy controls. The specific aims are 1) to
investigate if MBV is reduced in NOCAD patients at baseline, 2) to investigate
if MBV is reduced in NOCAD patients during hyperinsulinemia and 3) to
investigate if MBV is reduced in NOCAD patients during increased myocardial
contraction.
Study design
The study is an observational cross-sectional cohort study. The patient group
will undergo CFR measurement and coronary vasoreactivity testing during
coronary angiogram. Both groups will undergo myocardial contrast
echocardiography with an hyperinsulinemic euglycemic-clamp to induce
hyperinsulinemia and dobutamine to increase contractility, cardiac magnetic
resonance with T1-mapping and assessment of endothelial function in a
non-invasive way with EndoPAT.
Study burden and risks
Study subjects do not directly benefit from participation, besides their
contribution to increasing knowledge about NOCAD. Risks to participation are
medium. Disadvantages to participation are minimal but include time consumption
(i.e. 2 hospital visits) and uncomfortable feeling during adenosine or
dobutamine infusion and EndoPAT.
De Boelelaan 1117
Amsterdam 1007 MB
NL
De Boelelaan 1117
Amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
Patient group:
- Age > 40 years
- Signed informed consent
- Stable and chronic symptoms suggesting ischemic heart disease
- NOCAD on coronary angiography: coronary artery stenosis <= 50% and/or FFR >
0.80
- Prior transthoracic echocardiographic assessment
Control group:
- Age > 40 years
- Signed informed consent36 bgc
Exclusion criteria
- Age > 80 years
- Obstructive coronary artery disease, defined as more than 50% obstruction of
any coronary artery
- FFR < 0.80
- Use of medication for the control group
- Persons working at the department of Cardiology from the VU university
medical centre
- Persons involved in the study
- Family (partner, parents, child, brother or sister or statutory person) from
persons working at the department of Cardiology from the VU university medical
centre, or who are involved in the study
- Pregnancy
- History of coronary revascularization (e.g. percutaneous coronary
intervention or coronary artery bypass grafting)
- History of coronary artery disease, or acute coronary syndrome (e.g.
myocardial infarction and unstable angina pectoris)
- History of stroke
- History of cardiac arrhythmia*s
- History of heart valve disease
- Left ventricular dysfunction
- Congenital heart disease
- Insulin-dependent diabetes mellitus
- Extensive comorbidities (i.e. cancer, other chronic diseases)
- Impaired renal function, defined as creatinine > 100 and eGFR < 60.
- Symptomatic asthma or chronic obstructive pulmonary disease
- Known allergic reaction to contrast agent
- Insufficient echocardiographic imaging quality
- Contra-indications for CMR (e.g. severe claustrophobia, metal implants,
severe renal failure, severe asthma and known hypersensitivity for gadolinium)
- Contra-indications for microbubble usage (e.g. right-to-left shunt, severe
pulmonary hypertension, uncontrolled hypertension and adult respiratory
distress syndrome)
- Contra-indications for adenosine usage (e.g. hypersensitivity to active
substances, second or third degree atrio-ventricular block, sick sinus
syndrome, long QT syndrome, severe hypertension, concomitant use of
dipyridamole)
- Contra-indications for dobutamine usage (e.g. hypersensitivity to dobutamine,
severe heart failure, acute pericarditis, myocarditis or endocarditis, aortic
dissection or aneurysm, inadequately controlled arterial hypertension or
hypotension, hypovolemia)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL66532.029.18 |