COVID-19 has appeared as a game changer in the world, affecting millions of people with a wide range of symptoms, as well as late complications some of which are surprisingly frequent and life-threatening. Acute cardiac and vascular involvement in COVID-19 infection was reported in mostly hospitalized cases: myocarditis, acute coronary syndrome, pulmonary thromboembolism, cerebrovascular events etc. Although acute coronary syndrome was relatively rare at initial presentation or during hospitalisation, it could even affect patients with no obstructive coronary disease [5]. Endothelial disfunction, progression of atheromatous plaque formation, emotional factors or hypoxia causing autonomous disfunction, increased sympathetic vasomotor tonus and diminished hemodynamics along with instability of the plaques caused by systemic inflammation were the pathophysiological mechanisms explained so far [6–8].
“Long-COVID” is the term referring to the clinical situation where signs or symptoms of acute COVID-19 have prolonged or new signs or symptoms developed over 12 weeks [9]. Chest pain was also defined as a possible component of “Long COVID” and many imaging studies have demonstrated that myocardial involvement existed in symptomatic patients in the late period [10–16].
Except from direct myocardial involvement, late coronary vascular events have also been demonstrated recently. A young female case has attended to hospital with chest pain 1 month later than recovery from severe respiratory syndrome caused by COVID-19. She had no previous history of cardiac disease or any known risk factors. Authors advocated that, as proven with adenosine stress cardiac myocardial MRI in this case, coronary microvascular ischaemia may have been the mechanism of persistent chest pain after recovery from COVID-19 [17]. Another case report presented a similar scenario on a young male patient, with gradually progressive dispnea on exercise. He was then diagnosed with acute cardiac failure due to nonobstructive coronary artery disease presenting with extensive myocardial infarction [18]. In our study, the indication of MPS was most commonly dispnea, but not chest pain. This finding actually points a gap in the literature. Dispnea may exist as a component of Long COVID in up to 40% of cases [19]. However, its relation to coronary vascular involvement is still unclear.
Myocardial perfusion scintigraphy is the most frequently used functional imaging tool for assessing obstructive coronary artery disease risk. There exists a small amount of articles studying myocardial perfusion scintigraphy in COVID-19 patients.
Hasnie et al have performed stress testing and myocardial perfusion imaging in 15 patients after recovery from COVID-19 and stated that both regadenoson and exercise stress tests were safe and stress myocardial perfusion scan can be used reliably in evaluation of ischemic heart disease after COVID-19 infection [20].
Hasnie et al. and Nappi et al have hypothesized that the percentage of abnormal myocardial perfusion images would increase in the pandemic period, because those who have mild symptoms and a probably normal SPECT MPI would delay their examinations. However, no such significant increase was observed [3, 21].
The aim of this study was different than these previous reports, we focused only on patients with COVID-19 history and documented the increase in the incidence of ischemia demonstrable by MPS, compared to non-infected cohort. Although stent implentation was performed only in 2/39 and CABG in 1/39 patients, ischemia was evident on myocardial perfusion scan in these patients. Keeping all other risk factors constant among the study and control group, COVID-19 has appeared as the possible reason for this difference in the frequency of ischemia between the study and the control group. Demonstration of ischemia reflects the functional changes in myocardial blood flow with stress, which supports the reported clinical cases and previously suggested possible pathophysiological mechanisms affecting myocardial blood flow after COVID-19 infection [5]. One patient with no previous history of coronary artery disease or any mentioned risk factors who come up with ischemia on MPS after recovery from COVID-19 is also meaningful considering the case reports mentioned above. The frequency of obstructive coronary disease indicating coronary interventions could be expected to be higher after COVID-19, concerning these microvascular endothelial changes, but it was found similar to the control group. Incidence of hospital admissions with acute MI was reported to be higher than the pre-pandemic period, but incidence of ischemia was not studied before [2]. Our results suggest that together with acute coronary syndromes, as a reflection of coronary disfunction after recovery from COVID-19, ischemia on myocardial perfusion scan induced by stress testing is also more frequent compared to non-infected matched group of patients.
In clinical practice, MPS results guide patient evaluation by determining coronary artery risk. In our study, the number of coronary angiographies performed was higher in the study group. Initiation of medical therapy or invasive revascularisation therapies (stent implantation or CABG) were also higher in patients after recovery from COVID-19. We believe that this finding deserves attention as there are no similar results reported before, keeping in mind that obviously we are still lack of evidence to talk about a direct causal relationship between symptomatic COVID-19 infection and coronary artery disease. The reason why we couldn’t demonstrate such an increase in patients with ischemia (a statistically nonsignificant increase in frequency of initiation of treatment still exists, with a p = 0.06, Table 3) but generally in the whole study group regardless of the MPS results, may be the five patients in the ischemia group who didn’t accept to undergo CAG.
The main limitation of this study was its retrospective design. Loss of patient data and follow up results led to a relative decrease in the number of subjects included. Further prospective studies are necessary to confirm above mentioned results. Another thing is that COVID-19 is still a matter of debate with multiple unexplained issues in clinical practice. Together with vaccines and treatment methods, diagnosis and imaging remain an important area of clinical investigation to better understand and make provisions against late complications.