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

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.

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