Background – Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and is primarily characterised by a respiratory disease. However, SARS-CoV-2 can directly infect vascular endothelium and subsequently cause vascular inflammation, atherosclerotic plaque instability and thereby result in both myocardial inflammation and infarction. Interestingly, up to 70% of patients suffer from persistent exercise dyspnoea and a post-viral fatigue syndrome (PVFS) after having overcome an acute COVID-19 infection. In the present study, we assessed the presence of microvascular disease by cardiovascular magnetic resonance (CMR) in post-COVID-19 patients still suffering from exercise dyspnoea and a PVFS.

Methods – N=22 patients who recently recovered from COVID-19 and N=17 healthy control patients without relevant cardiac disease underwent dedicated vasodilator-stress CMR studies on a 1.5-T MR scanner. The CMR protocol comprised cine and late-gadolinium-enhancement (LGE) imaging as well as velocity-encoded (VENC) phase-contrast imaging of the coronary sinus flow (CSF) at rest and during pharmacological stress (maximal vasodilation induced by 400µg IV regadenoson). Using CSF measurements at rest and during stress, coronary flow reserve (CFR) was calculated.

Results – There was no difference in left ventricular ejection-fraction (LV-EF) between COVID-19 patients and controls (60% [57-63%] vs. 63% [60-66%], p=NS). There were only N=4 COVID-19 patients (18%) showing a non-ischemic pattern of LGE. VENC-based flow measurements showed that CSF at rest was higher in COVID-19 patients compared to controls (1.78 ml/min [1.19 - 2.23 ml/min] vs. 1.14 ml/min [0.91 – 1.32 ml/min], p=0.048). In contrast, CSF during stress was lower in COVID-19 patients compared to controls (3.33 ml/min [2.76 – 4.20 ml/min] vs. 5.32 ml/min [3.66 – 5.52 ml/min], p=0.05). A significantly reduced CFR was calculated in COVID-19 patients compared to healthy controls (2.73 [2.10-4.15-11] vs. 4.82 [3.70-6.68], p=0.005).

Conclusion – In post-COVID-19 patients with persistent exercise dyspnoea and PVFS, a tremendously reduced CFR suggestive of microvascular disease was observed in the present study. A reduction in CFR can be caused by preceding SARS-CoV-2-associated coronary vessel inflammation and/or myocardial inflammation, and may explain ongoing symptoms of exercise dyspnoea and PVFS in some patients after COVID-19 infection.

Key words: MVD, CMD, CMR, COVID-19, HCM, CSF