Microvascular Disease Exercise Trial
| Status: | Active, not recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - 85 |
| Updated: | 5/18/2018 |
| Start Date: | May 2014 |
| End Date: | July 2021 |
Assessment of Perfusion Reserve and Effects of Exercise in Microvascular Angina
For part of this study, we are collecting information from patients that have been
experiencing the symptoms mentioned above. We are taking this information and creating a
chest pain registry to follow trends and compare different patients having similar symptoms.
We hope to gain insight into the quality of life, symptoms, and cardiac events of those who
are having similar symptoms. The type of information we will collect includes: demographics,
quality of life, levels of anxiety related to angina pain and cardiac events occurring within
a 2 year period of time.
In addition, we are performing a cardiac stress MRI for research purposes to look at the
blood flow in the small vessels in your heart. During the stress cardiac MRI, we will give
you a medication called Regadenoson (Lexiscan) which "stresses" your heart by dilating the
blood vessels to your heart. This drug is approved by the U.S. Food and Drug Administration
(FDA) for this purpose. We will then be able to measure the myocardial perfusion reserve
(MPR) which is a measure of blood flow through the small blood vessels to see if an abnormal
MPR and small blood vessel disease is associated with an increased risk of cardiovascular
events, such as heart attack. At this point, there is no specific therapy for small vessel
disease. In addition we have phase II of this study which is to determine if exercise and
intensive medical therapy together compared to intensive medical therapy alone improves pain
from the heart and improves overall quality of life.
experiencing the symptoms mentioned above. We are taking this information and creating a
chest pain registry to follow trends and compare different patients having similar symptoms.
We hope to gain insight into the quality of life, symptoms, and cardiac events of those who
are having similar symptoms. The type of information we will collect includes: demographics,
quality of life, levels of anxiety related to angina pain and cardiac events occurring within
a 2 year period of time.
In addition, we are performing a cardiac stress MRI for research purposes to look at the
blood flow in the small vessels in your heart. During the stress cardiac MRI, we will give
you a medication called Regadenoson (Lexiscan) which "stresses" your heart by dilating the
blood vessels to your heart. This drug is approved by the U.S. Food and Drug Administration
(FDA) for this purpose. We will then be able to measure the myocardial perfusion reserve
(MPR) which is a measure of blood flow through the small blood vessels to see if an abnormal
MPR and small blood vessel disease is associated with an increased risk of cardiovascular
events, such as heart attack. At this point, there is no specific therapy for small vessel
disease. In addition we have phase II of this study which is to determine if exercise and
intensive medical therapy together compared to intensive medical therapy alone improves pain
from the heart and improves overall quality of life.
Cardiac angina is a major source of morbidity, affecting more than 5% of the U.S.
population.2 It leads to more than 1.5 million hospitalizations and $190 billion in costs
yearly.3 Obstructive coronary artery disease (CAD) is the most common cause of angina.
However, no obstructive CAD is found on elective coronary angiography in more than 50% of
cases.4, 5 These patients with angina but no obstructive CAD are a heterogeneous group. Some
have noncardiac explanations for their angina or nonobstructive epicardial abnormalities such
as coronary spasm. However, many patients with angina and no obstructive CAD have
microvascular dysfunction from endothelial dysfunction or microvascular obstructive disease
as the cause. These patients have microvascular angina.
The coronary microvasculature is responsible for more than 70% of coronary resistance and
thus plays a key role in regulating blood flow to match demand.6 Microvascular dysfunction
can occur in the setting of dilated, hypertrophic, and restrictive cardiomyopathies. However,
it is commonly seen in the setting of atherosclerotic risk factors or can be idiopathic.6, 7
Microvascular dysfunction is manifest as insufficient stress myocardial blood flow and/or
reduced myocardial perfusion reserve (MPR), the ratio of stress flow to rest flow, in
response to a stress such as vasodilator administration. Absolute myocardial blood flow and
MPR can be assessed noninvasively with high precision and accuracy by cardiac magnetic
resonance (CMR) imaging Reduced MPR in patients with angina is associated with significant
morbidity, including a high risk of cardiac events, high medical costs, and a decreased
quality of life.Despite the poor prognosis of this population, therapeutic options to reduce
angina and improve MPR have not been well studied. Preliminary analysis shows that statins
may improve endothelial function. ACE-inhibitors and beta-blockers improve symptoms in
Syndrome X, a related disorder in which patients have angina, no obstructive CAD, and
ischemic changes but a better prognosis. Therapeutic exercise has also been used in the
Syndrome X population, improving exercise tolerance and endothelial function and reducing
symptom severity.Improvements in MPR could be expected with exercise due to the reduced
resting flow and increased MPR seen in healthy volunteers and improved endothelial function
from increased nitric oxide bioactivity in patients with probable microvascular dysfunction.
However, no studies have examined the effect of these medications or their synergism with
exercise on MPR, aerobic capacity, anginal symptoms, or quality of life in patients with
angina and reduced MPR. Identification of an effective therapy that improved symptoms and
prognosis would have dramatic impact on this highly prevalent patient population.
The primary goal of this study is to characterize which patients with angina but no
obstructive CAD have reduced MPR and test the effectiveness of intensive medical therapy plus
a 12-week supervised exercise program versus intensive medical therapy alone to improve MPR,
aerobic capacity, and the patient-centered outcomes of cardiac events, angina severity, and
quality of life in this population with microvascular angina.
population.2 It leads to more than 1.5 million hospitalizations and $190 billion in costs
yearly.3 Obstructive coronary artery disease (CAD) is the most common cause of angina.
However, no obstructive CAD is found on elective coronary angiography in more than 50% of
cases.4, 5 These patients with angina but no obstructive CAD are a heterogeneous group. Some
have noncardiac explanations for their angina or nonobstructive epicardial abnormalities such
as coronary spasm. However, many patients with angina and no obstructive CAD have
microvascular dysfunction from endothelial dysfunction or microvascular obstructive disease
as the cause. These patients have microvascular angina.
The coronary microvasculature is responsible for more than 70% of coronary resistance and
thus plays a key role in regulating blood flow to match demand.6 Microvascular dysfunction
can occur in the setting of dilated, hypertrophic, and restrictive cardiomyopathies. However,
it is commonly seen in the setting of atherosclerotic risk factors or can be idiopathic.6, 7
Microvascular dysfunction is manifest as insufficient stress myocardial blood flow and/or
reduced myocardial perfusion reserve (MPR), the ratio of stress flow to rest flow, in
response to a stress such as vasodilator administration. Absolute myocardial blood flow and
MPR can be assessed noninvasively with high precision and accuracy by cardiac magnetic
resonance (CMR) imaging Reduced MPR in patients with angina is associated with significant
morbidity, including a high risk of cardiac events, high medical costs, and a decreased
quality of life.Despite the poor prognosis of this population, therapeutic options to reduce
angina and improve MPR have not been well studied. Preliminary analysis shows that statins
may improve endothelial function. ACE-inhibitors and beta-blockers improve symptoms in
Syndrome X, a related disorder in which patients have angina, no obstructive CAD, and
ischemic changes but a better prognosis. Therapeutic exercise has also been used in the
Syndrome X population, improving exercise tolerance and endothelial function and reducing
symptom severity.Improvements in MPR could be expected with exercise due to the reduced
resting flow and increased MPR seen in healthy volunteers and improved endothelial function
from increased nitric oxide bioactivity in patients with probable microvascular dysfunction.
However, no studies have examined the effect of these medications or their synergism with
exercise on MPR, aerobic capacity, anginal symptoms, or quality of life in patients with
angina and reduced MPR. Identification of an effective therapy that improved symptoms and
prognosis would have dramatic impact on this highly prevalent patient population.
The primary goal of this study is to characterize which patients with angina but no
obstructive CAD have reduced MPR and test the effectiveness of intensive medical therapy plus
a 12-week supervised exercise program versus intensive medical therapy alone to improve MPR,
aerobic capacity, and the patient-centered outcomes of cardiac events, angina severity, and
quality of life in this population with microvascular angina.
Inclusion Criteria:
- Age 18 - 85
- Anginal symptoms of chest pain, dyspnea on exertion, or other anginal equivalent
suspected to be secondary to myocardial ischemia
- Coronary angiogram without obstructive epicardial coronary artery disease (≥50%
epicardial stenosis or fractional flow reserve of <0.80) within 6 months prior to
enrollment or date of CMR #1, whichever is later and without intervening signs or
symptoms suggestive of new obstructive epicardial CAD.
Exclusion Criteria:
- Prior CABG (due to limitations of CMR quantitative perfusion in this population)
- Prior myocardial infarction (due to its effects on myocardial flow reserve)
- Hypertrophic or restrictive cardiomyopathy
- Coronary vasospasm
- Acute coronary syndrome unless concurrent coronary angiography reveals no epicardial
stenoses of >50%
- Contraindications to CMR including - intracranial aneurysm clips, implantable
pacemaker or defibrillator, metal cochlear/intraocular implants, any metallic implant
not listed as magnetic resonance compatible, severe claustrophobia or other inability
to tolerate a 30 minute CMR study
- GFR < 45 ml/min/1.73² (to avoid nephrogenic systemic fibrosis and iodinated contrast
dye - mediated ATN) based on creatinine within 30 days of CMR #1
- Acute kidney injury, defined by the KDIGO Clinical Practice Guidelines as an increase
in serum creatinine of ≥0.3 mg/dL within 48 hours, an increase in serum creatinine
≥1.5 times baseline thought to have occurred in the past 7 days, or a urine volume
<0.5mL/kg/h for 6 hours
- Severe liver disease, paraproteinemia syndromes (such as multiple myeloma),
hepatorenal syndrome, or planned liver transplantation (gadolinium contraindication)
- Pregnancy (assessed by serum beta- HCG prior to CMR) due to unclear gadolinium fetal
effects
- Known hypersensitivity to regadenoson, or gadolinium
- Other contraindications to regadenoson (heart rate < 40 bpm, 2nd or 3rd degree heart
block, sick sinus syndrome without a pacemaker, severe asthma or COPD with ongoing
wheezing or hospitalization within the past 6 months, systolic blood pressure <90mmHg,
recent use of dipyridamole, methylxanthine (such as aminophylline) or dipyridamole use
within the past 48 hours, or caffeine within 12 hours)
- Atrial fibrillation with rapid ventricular response, frequent ectopy, or other
contraindications to ECG gating
- Inability to provide informed consent
- Life expectancy of < 2 years
3. List any restrictions on use of other drugs or treatments.
- Subject will be asked to refrain from use of caffeine for 12 hours and methylxanthines
and dipyridamole for 48 hours prior to any administration of regadenoson. Subject may
not participate if pregnant or breastfeeding.
Phase 2:
1. List the criteria for inclusion
- Enrollment in phase #1.
- MPR <2.0 ml/g/min on CMR #1.
2. List the criteria for exclusion
•Unable to exercise.
3. List any restrictions on use of other drugs or treatments. Subject will be asked to
refrain from use of caffeine for 12 hours and methylxanthines and dipyridamole for 48
hours prior to any administration of regadenoson. Subject may not participate if
pregnant or breastfeeding.
We found this trial at
2
sites
Charlottesville, Virginia 22903
(434) 924-0311
Principal Investigator: Jamieson Bourque, MD, MHS
Phone: 434-982-1058
University of Virginia The University of Virginia is distinctive among institutions of higher education. Founded...
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University of Virginia The University of Virginia is distinctive among institutions of higher education. Founded...
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