Potential Role of ¹³N-NH₃ Cardiac PET in Monitoring Treatment Response in Patients with Microvascular Angina

Introduction

Over the past few decades, there has been increasing recognition of patients with ischemia with nonobstructive coronary artery disease (INOCA) (i.e., symptoms of myocardial ischemia in the absence of obstructive coronary artery disease [CAD]).[1] Coronary microvascular dysfunction (CMD) is one of the underlying causes of INOCA and exhibits an increased incidence of major adverse cardiac events (MACE).[2] The definitive diagnosis of CMD depends on the demonstration of impaired coronary flow reserve at invasive coronary angiography (CAG).[3] However, it is invasive, expensive, and associated with significant radiation exposure. We hereby report a patient with angina and nonobstructive coronaries, having impaired myocardial flow reserve (MFR) and perfusion defects at cardiac PET. The patient demonstrated improvement in myocardial perfusion and dynamic PET parameters following medical management, thus highlighting the potential role of PET in monitoring treatment response in such patients.

Case Report

A 68-year-old man presented to the cardiology department with complaints of intermittent precordial chest discomfort over the past few months. Besides hypertension, the patient had no other notable cardiovascular risk factors including diabetes, hyperlipidemia, smoking, or a family history of CAD. The resting 12-lead electrocardiography (ECG) revealed an incidental left anterior fascicular block. Transthoracic echocardiography was unremarkable with an ejection fraction of 60%–65%. On CAG, no obstructive CAD was noted. Nevertheless, mild ectasia of the proximal left anterior descending artery (LAD) was observed, with the diagonal vessel originating from the middle of the ectatic LAD segment [Figure 1].

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Figure 1 Coronary angiogram in cranial anteroposterior projection (a) and caudal right anterior oblique projection (b) showing mild ectasia of the proximal left anterior descending artery (LAD) (arrowheads), with the diagonal vessel originating from the middle of the ectatic LAD segment (arrow). No obstructive coronary artery disease was noted at coronary angiography

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Given suspected microvascular angina, the patient was referred for PET myocardial perfusion imaging using ¹³N-Ammonia. Before the procedure, the patient was instructed to refrain from consuming any caffeinated products and to avoid taking beta-blockers, calcium channel blockers, and aminophylline medications for a minimum of 24–48 h before the study. Myocardial blood flow (MBF) quantification was obtained using a dynamic rest and stress protocol. To induce hyperemia, adenosine was administered intravenously at a rate of 140 µg/kg/min for 6 min and the continuous ECG obtained during the adenosine stress showed no significant ST segment changes. Rest and poststress images, reconstructed in short axis, vertical, and horizontal long axes, demonstrated reversible perfusion defect of moderate severity involving the apex, anterior, and anterolateral walls [Figure 2]. In addition, both hyperaemic MBF and MFR were also reduced (MFR <2.0) in the LAD and left circumflex territories. An MFR cutoff of 2.0 is routinely used in our practice to identify patients with CMD, consistent with findings from previous studies.[45]

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Figure 2 Dynamic rest and poststress myocardial perfusion images (a) obtained after intravenous injection of ¹³N-ammonia, reconstructed in short axis, vertical, and horizontal long axis depicting reversible perfusion defect (arrows) of moderate-to-severe intensity involving the apex, anterior, and anterolateral walls. Global and regional stress and rest myocardial blood flow (MBF) and myocardial flow reserve (MFR) values (b) and motion corrected stress and rest time activity curves depicting reduced hyperemic MBF and MFR in the left anterior descending and left circumflex territories

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Considering the patient’s symptoms, cardiac PET findings, and the lack of obstructive CAD at angiography, a diagnosis of microvascular angina was established and medical management was initiated. The treatment plan included a combination of aspirin with low-dose statin and ranolazine. In addition, beta-blockers and angiotensin receptor blockers were continued to manage hypertension. At the 3-month follow-up, the patient reported improvement in symptoms and increased exercise tolerance. The patient was advised to continue the ongoing treatment. A subsequent cardiac PET scan performed at 1 year displayed improvements in stress MBF and MFR values (>2.5), along with the disappearance of the reversible perfusion abnormality noted at the baseline PET [Figure 3].

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Figure 3 Follow-up performed at 1 year depicting normal myocardial perfusion (a) and normal stress myocardial blood flow (MBF) and myocardial flow reserve (MFR) values (b). Compared to baseline positron emission tomography (PET) in Figure 2, there is a disappearance of the reversible ischemia and an improvement in dynamic PET parameters (i.e., stress MBF and MFR)

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CMD is one of the underlying causes of INOCA and is associated with an increased incidence of MACE.[1] As per the Coronary Vasomotion Disorders International Study Group criteria, the definitive diagnosis of CMD/MVA requires the demonstration of reduced CFR at invasive CAG.[3] The present case highlights the potential role of cardiac PET not only in detecting CMD (through noninvasive MBF quantification) but also in monitoring response to medical therapy in such individuals.