Role of PET to evaluate coronary microvascular dysfunction in non-ischemic cardiomyopathies

Abstract

Coronary microvascular dysfunction (CMD) can result from structural and functional abnormalities at the intramural and small coronary vessel level affecting coronary blood flow autoregulation and consequently leading to impaired coronary flow reserve. CMD often co-exists with epicardial coronary artery disease but is also commonly seen in patients with various forms of heart disease, including dilated, hypertrophic, and infiltrative cardiomyopathies. CMD can go unnoticed without any symptoms, or manifest as angina, and/or dyspnea, and contribute to the development of heart failure, and even sudden death especially when co-existing with myocardial fibrosis. However, whether CMD in non-ischemic cardiomyopathy is a cause or an effect of the underlying cardiomyopathic process, or whether it can be potentially modifiable with specific therapies, remains incompletely understood.

Keywords: Cardiac PET; Coronary flow reserve; Coronary microvascular dysfunction; Non-ischemic cardiomyopathy.

Figure 1.. Microvascular dysfunction may potentiate hypertrophy, fibrosis and atherosclerosis.

In health (left panel), a balance of NO (nitric oxide), prostacyclin (PGI2), and epoxyeicosatrienoic acids (EETs) and low levels of hydrogen peroxide support a quiescent nonproliferative state. With onset of disease (right panel), hydrogen peroxide released from the microvasculature can create a proinflammatory environment and lead to hypertrophy, fibrosis, and atherosclerosis. Figure reproduced with permission from reference.[1]

Figure 2.. Transthoracic echocardiography and rest-regadenoson N-13 ammonia PET/CT in a 75 year-old male with idiopathic non-ischemic dilated cardiomyopathy.

Patient initially presented with syncope due to sustained ventricular tachycardia. Echocardiography showed a severely dilated left ventricle with severely reduced systolic function. Cardiac PET showed no definite evidence of vasodilator-induced myocardial ischemia. However, global peak hyperemic myocardial blood blow was moderate to severely reduced, and coronary flow reserve was mildly impaired. Invasive coronary angiography demonstrated normal epicardial coronary arteries. Overall, findings were consistent with a form of non-ischemic dilated cardiomyopathy with associated coronary microvascular dysfunction.

Figure 3.. Rest-Regadenoson N-13 ammonia PET/CT in a 22 yr old man with hypertrophic cardiomyopathy

A 22 yr old man with known hypertrophic cardiomyopathy without LVOT obstruction and ongoing chest discomfort was referred for rest and regadenoson N-13 ammonia PET/CT for evaluation of coronary microvascular dysfunction. Stress and rest images are shown in alternate rows with short axis images (top two rows) from apex to base (left to right), horizontal long axis images (middle two rows) from the inferior to the anterior wall (left to right), and vertical long axis images (bottom two rows) from the septum to the lateral wall (left to right). On the right bottom panel, stress, rest, and reversibility polar plots (top row) and summed stress, summed rest and summed difference scores are shown (bottom panel). LVEF declined from 56% at rest to 39% after vasodilator stress. Peak hyperemic myocardial blood flow and coronary flow reserve (CFR) were substantially reduced for age. Coronary CT angiography shows normal epicardial coronary arteries with prominent myocardial crypts in the mid portion of the anterior wall.

Figure 4.. Cardiac magnetic resonance and rest-regadenoson N-13 ammonia PET/CT in a patient with apical-variant hypertrophic cardiomyopathy.

Patient is a 40 year-old male who presented with significant exertional chest pain, and functional class III. He had angiographically normal epicardial coronary arteries. However, cardiac magnetic resonance (CMR) imaging revealed classic appearance of apical-variant hypertrophic cardiomyopathy with significant late gadolinium enhancement (LGE) mostly confined to the hypertrophic apex. On further evaluation, N-13 ammonia PET showed evidence of significant vasodilator-induced ischemia and coronary microvascular dysfunction particularly at the apex.

Figure 5.. Rest-Dipyridamole N-13 ammonia PET/CT in a 68 yr old man with light chain amyloidosis.

A 68 yr old man with known systemic and cardiac light chain amyloidosis was referred for evaluation of coronary microvascular dysfunction as part of a research study. Epicardial CAD was excluded by coronary CT angiography. Rest and dipyridamole stress N-13 ammonia PET/CT was performed at baseline (Panel A) and followup images 6 months after completion of chemotherapy (Panel B). Perfusion images are displayed as described in Figure 3. Peak hyperemic myocardial blood flow and coronary flow reserve (CFR) were substantially reduced at baseline and improved significantly on follow-up (although still abnormal).