Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03249272
Recruitment Status : Recruiting
First Posted : August 15, 2017
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Duke University

Brief Summary:
The aim of this study is to assess microvascular function as determined by a cardiovascular magnetic resonance measurement of whole-heart (global) perfusion reserve. The goal is to determine the prevalence of MVD in two common forms of non-ischemic cardiomyopathy, hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (IDCM). The hypothesis that an optimized technique will provide robust detection of MVD and that a multifaceted approach will provide new insights into the pathophysiology of MVD, including the influence of myocardial scarring upon the presence and severity of MVD.

Condition or disease Intervention/treatment Phase
Hypertrophic Cardiomyopathy Non-ischemic Dilated Cardiomyopathy Microvascular Ischaemia of Myocardium Drug: Regadenoson Drug: Adenosine Phase 4

Detailed Description:

Coronary microvascular dysfunction (MVD) has been implicated as an important marker of cardiac risk and has been thought to directly contribute to the pathogenesis of a wide variety of cardiomyopathies. For instance, MVD is believed to cause ischemia (with reduction in coronary flow reserve) in patients with hypertrophic cardiomyopathy (HCM) despite the presence of angiographically normal epicardial coronary arteries. The implication is that MVD in HCM may lead to the ventricular arrhythmias, sudden death, and heart failure. Similarly, patients with idiopathic dilated cardiomyopathy (IDCM) have blunted coronary flow reserve, which appears to be independently associated with poor prognosis.

Several etiologic mechanisms have been proposed to explain the occurrence of MVD, including structural and functional abnormalities1:

  1. increased microvascular resistance due to reduced vascular luminal caliber.
  2. reduced density of microvessels associated with replacement scarring.
  3. inappropriate vasoconstrictor responses.
  4. inadequate vasodilator responses.

Unfortunately, these mechanisms are difficult to study in humans since no technique currently allows the direct visualization of the coronary microcirculation in vivo. Thus, MVD has been largely studied using non-invasive imaging techniques, such as positron emission tomography (PET) or single photon emitted computed tomography (SPECT).

Although these methods have provided insight into MVD, much remains unknown. For example, even the prevalence of MVD in patients with various types of cardiomyopathy is unclear, with different studies showing widely different rates.

Cardiovascular magnetic resonance (CMR) is increasingly being used in clinical practice to evaluate cardiac disease. CMR employs a multifaceted imaging approach with separate techniques used to acquire separate sets of raw data, providing information on cardiac morphology, function, regional myocardial ischemia, scarring, and global myocardial perfusion reserve. The advantage of this approach is that image artifacts in one set of data will not affect the quality of the other datasets, and the datasets in combination can be used to distinguish separate pathophysiologies that could confound image interpretation. For example, perfusion defects could be due to ischemia or scar tissue, but since the investigators will obtain both perfusion images and scar images, the investigators will be able to resolve the etiology. Additionally, CMR provides high spatial resolution (over 10-fold higher than PET), and hence partial volume affects will be kept to a minimum and variability in measurements will be reduced.

The aim of this study is to assess microvascular function as determined by a cardiovascular magnetic resonance measurement of whole-heart (global) perfusion reserve. The goal is to determine the prevalence of MVD in two common forms of non-ischemic cardiomyopathy, hypertrophic cardiomyopathy (HCM) and idiopathic dilated cardiomyopathy (IDCM). The hypothesis that an optimized technique will provide robust detection of MVD and that a multifaceted approach will provide new insights into the pathophysiology of MVD, including the influence of myocardial scarring upon the presence and severity of MVD.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Participants undergoing cardiovascular magnetic resonance stress testing will be recruited and randomized to receive either regadenoson or adenosine.
Masking: Single (Outcomes Assessor)
Masking Description: The reader of the CMR scan will be blinded to the stress agent used.
Primary Purpose: Basic Science
Official Title: Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve
Actual Study Start Date : September 5, 2017
Estimated Primary Completion Date : September 21, 2019
Estimated Study Completion Date : September 21, 2019


Arm Intervention/treatment
Active Comparator: Hypertrophic cardiomyopathy Drug: Regadenoson
The coronary flow reserve measured by CMR that is induced by regadenoson versus adenosine will be compared.

Drug: Adenosine
The coronary flow reserve measured by CMR that is induced by regadenoson versus adenosine will be compared.

Active Comparator: Non-ischemic dilated cardiomyopathy Drug: Regadenoson
The coronary flow reserve measured by CMR that is induced by regadenoson versus adenosine will be compared.

Drug: Adenosine
The coronary flow reserve measured by CMR that is induced by regadenoson versus adenosine will be compared.

Active Comparator: Atypical chest pain Drug: Regadenoson
The coronary flow reserve measured by CMR that is induced by regadenoson versus adenosine will be compared.

Drug: Adenosine
The coronary flow reserve measured by CMR that is induced by regadenoson versus adenosine will be compared.




Primary Outcome Measures :
  1. Prevalence of microvascular dysfunction (MVD) by a CMR measurement of whole-heart (global) perfusion reserve ratio in patients with hypertrophic cardiomyopathy, non-ischemic cardiomyopathy, and atypical chest pain. [ Time Frame: Baseline ]
    We are measuring CMR measure of global perfusion reserve ratio in each these patient groups.


Secondary Outcome Measures :
  1. CMR measurement of global perfusion reserve ratio [ Time Frame: Baseline ]
  2. The association between global perfusion reserve ratio and other CMR metrics including regional myocardial scarring and perfusion as measured by odds ratio as appropriate. [ Time Frame: Baseline ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Men or women aged 18 years or older

Cardiomyopathy patients

  • Patients presenting for CMR with the clinical diagnosis of hypertrophic cardiomyopathy based on left ventricular wall thickness of at least ≥15 mm in the absence of any other cardiac or systemic cause of hypertrophy
  • Patients presenting for CMR with the clinical diagnosis of idiopathic dilated cardiomyopathy based upon left ventricular ejection fraction ≤40%, LV end-diastolic diameter ≥55 mm or left ventricular end-systolic diameter ≤45 mm, and the absence of coronary stenoses on angiography.

Control patients with atypical chest pain

  • Patients presenting for CMR evaluation of chest pain but without evidence of obstructive coronary artery disease either by coronary angiography or stress testing.

Exclusion Criteria:

  • Decompensated heart failure or hemodynamic instability
  • Prior coronary revascularization (PCI or CABG) or myocardial infarction (as evidenced by previously elevated CPK-MB or troponin levels)
  • Accelerating angina or unstable angina
  • Inability to physically tolerate MRI or implanted objects that are MRI incompatible
  • Inability to provide written informed consent obtained at time of study enrollment.
  • Severe claustrophobia
  • Advanced heart block or sinus node dysfunction
  • Hypersensitivity or allergic reaction to regadenoson or adenosine
  • Hypotension
  • Active bronchospasm or history of hospitalization due to bronchospasm
  • History of seizures
  • Recent cerebrovascular accident
  • Use of dipyridamole within the last 5 days
  • Contraindication to aminophylline
  • Severe renal insufficiency with estimated glomerular filtration rate <30 ml/min/ 1.73 m2
  • Pregnant or nursing

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03249272


Contacts
Layout table for location contacts
Contact: Han Kim, MD 919-668-3539 han.kim@duke.edu

Locations
Layout table for location information
United States, North Carolina
Duke Cardiovascular Magnetic Resonance Center Recruiting
Durham, North Carolina, United States, 27110
Contact: Han Kim, MD         
Sponsors and Collaborators
Duke University
Investigators
Layout table for investigator information
Principal Investigator: Han Kim Duke University

Publications:
Layout table for additonal information
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT03249272     History of Changes
Other Study ID Numbers: Pro00082447
First Posted: August 15, 2017    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Cardiomyopathies
Cardiomyopathy, Hypertrophic
Cardiomyopathy, Dilated
Ischemia
Pathologic Processes
Heart Diseases
Cardiovascular Diseases
Aortic Stenosis, Subvalvular
Aortic Valve Stenosis
Heart Valve Diseases
Cardiomegaly
Adenosine
Regadenoson
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adenosine A2 Receptor Agonists