Myocardial Perfusion Reserve Quantified by Stress Cardiovascular Magnetic Resonance Imaging is Reduced in Long COVID Patients Presenting With Chest Pain

Introduction: Chest pain is common in patients with Post-acute Sequelae of SARS-CoV-2 (PASC), also known as long COVID, but the mechanism is unknown. Hypothesis: We hypothesized that PASC patients with chest pain have impaired myocardial perfusion reserve (MPR) measured by stress perfusion cardiovascular magnetic resonance (CMR) imaging. Methods: We retrospectively identified the first 30 consecutive patients who underwent clinically ordered adenosine stress perfusion CMR for chest pain persisting >4 weeks after SARS-CoV-2 infection (PASC). Patients with a history of coronary artery disease (CAD) or left ventricular ejection fraction (LVEF) <50% were excluded. Patients without a history of SARS-CoV-2 infection who had a normal clinically ordered perfusion CMR served as controls. A previously-described automated pixel-wise quantitative perfusion tool was used to calculate stress and rest myocardial blood flow (MBF) in mL/min/g, and MPR as the ratio of stress MBF/rest MBF. The cutoff for reduced MPR was >2 SD below mean MPR for controls. Results: In 30 PASC (67% female, age 43±13) and 13 controls (54% female, age 50±12), with LVEF (61±6% vs 59±8%), native T1 (1001±49 vs 992±57 ms), T2 (49.5±3.7 vs 48.0±3.3 ms), and ECV (24.6±2.9 vs 24.6±2.6%) were similar (p>0.2 for all). Prior pericarditis (n=2) or prior myocarditis (n=3) were infrequent, with no acute disease by CMR. PASC patients had significantly lower global MPR than controls (1.54±0.25 vs. 2.20±0.36, p<0.001), and 16/30 (53%) PASC patients had reduced MPR (<1.49). Clinical ischemia evaluation revealed obstructive CAD in only 2 PASC patients. Conclusions: In PASC patients with chest pain undergoing stress perfusion CMR, global MPR is frequently reduced and is significantly lower than in patients with normal clinical perfusion CMR and no history of SARS-CoV-2 infection. This study raises the possibility that microvascular dysfunction is an important cause of chest pain in patients with long COVID.