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

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

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

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.

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: increased microvascular resistance due to reduced vascular luminal caliber. reduced density of microvessels associated with replacement scarring. inappropriate vasoconstrictor responses. 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.

Hypertrophic Cardiomyopathy, Non-ischemic Dilated Cardiomyopathy, Microvascular Ischaemia of Myocardium

Participants undergoing cardiovascular magnetic resonance stress testing will be recruited and randomized to receive either regadenoson or adenosine.

Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.

Microvascular disease will be considered present if regional perfusion defects are observed or global perfusion reserve is reduced. For the assessment of microvascular disease, the adenosine and regadenoson groups will be combined, as the medications are considered interchangeable.

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 Controls.

Prevalence of microvascular dysfunction as determined by the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups. MVD was considered present when either GPR was <2.0 or regional stress perfusion abnormalities were present. In order to calculate this ratio, coronary sinus flow was measured twice: prior to the the administration of adenosine/regadenoson during the administration of adenosine/regadenoson GPR is a ratio of coronary sinus flow during the administration adenosine/regadenoson divided by the baseline coronary sinus flow measured prior to the administration. Regional perfusion abnormalities will be assessed at the time of adenosine/regadenoson administration.

The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study.

Comparison of the CMR measure of global perfusion reserve ratio (GPR) in each these patient groups. In order to calculate this ratio, coronary sinus flow was measured twice: prior to the the administration of adenosine/regadenoson during the administration of adenosine/regadenoson

The global perfusion ratio will be calculated from the measurements obtained at the time of the scan on Day 1 of the study.

Both global perfusion ratio and the presence of regional scarring will be determined/measured from the images obtained during the scan on Day 1 of the study.

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 Patients presenting for CMR 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

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