Stress myocardial blood flow reduced after severe COVID-19, not related to symptoms
Authors: Doeblin P , Goetze C , Al-Tabatabaee S , Berger A , Steinbeis F , Witzenrath M , Faragli A , Stehning C , Chiribiri A , Scannell C M , Alskaf E , Pieske B , Kelle S 
Published: October 2021

Abstract

Introduction
Persistent cardiopulmonary symptoms after COVID-19 are reported in a large number of patients and the underlying pathology is still poorly understood. (1) Histopathologic studies revealed myocardial macrophage infiltrates in deceased patients, likely an unspecific finding of severe illness, and increased prevalence of micro- and macrovascular thrombi. (2) We examined whether microvascular perfusion, measured by quantitative cardiac magnetic resonance under vasodilator stress, was altered post COVID-19.

Methods
Our population consisted of 12 patients from the Pa-COVID-19-Study of the Charité Berlin, which received a cardiac MRI as part of a systematic follow up post discharge, 10 patients that presented at the German Heart Center Berlin with persistent cardiac symptoms post COVID-19 and 12 patients from the Kings College London referred for stress MRI and previous COVID-19.
The scan protocol included standard functional, edema and scar imaging and quantitative stress and rest perfusion to assess both macro- and microvascular coronary artery disease. The pharmacological stress agent was regadenosone in 20 and adenosine in 13 of the patients. To control for the higher heart rate increase under regadenosone compared to adenosine, we calculated the myocardial blood flow per heartbeat (MBF_HRi) under stress.

Results
The median time between first positive PCR for COVID-19 and the CMR exam was 2 months (Range 0 to 12). None of the 33 patients exhibited signs of myocardial edema. One patient with a previous history of myocarditis had focal fibrosis. Three patients with known coronary artery disease showed ischemic Late Enhancement. Five patients had a small pericardial effusion; one of these four patients showed slight focal pericardial edema and LGE, consistent with mild focal pericarditis. Five Patients had a stress-induced focal perfusion deficit.
Mean Stress MBF_HRi was 32.5±6.5 μl/beat/g. Stress MBF_HRi was negatively correlated with COVID-19 severity (rho=−0.361, P=0.039) and age (r=−0.452, P=0.009). The correlation with COVID-19 severity remained significant after controlling for age (rho=−0.390, P=0.027). There was no apparent difference in stress MBF_HRi between patients with and without persistent chest pain (34.5 vs. 31.5 μl/beat/g, P=0.229)

Conclusion
While vasodilator-stress myocardial blood flow after COVID-19 was negatively correlated to COVID-19 severity, it was not correlated to the presence of chest pain. The etiology of persistent cardiac symptoms after COVID-19 remains unclear.

Funding Acknowledgement
Type of funding sources: Private company. Main funding source(s): Philips Figure 1. A) Quantitative regadenosone stress myocardial blood flow (MBF) map, medial short axis slice, in a patient with persistent cardiac symptoms after COVID-19. B) Boxplot of stress MBF per heart beat by COVID-19 severity, showing decreasing MBF with increasing COVID-19 severity.