The present study demonstrated that patients referred to stress MPS for evaluation of suspected or known CAD, who presented COVID-19 infection during follow-up had a higher incidence of cardiac events compared to patients without subsequent COVID-19 infection. In particular, COVID-19 infection and abnormal MPS were both independent predictors of cardiac events at follow-up.
After its insurgence, COVID infection has spread to more than 200 countries, and mortality of the critical patients has been reported to be as high as 50% . Previous studies demonstrated that patients with COVID-19 infection and other comorbidities were more frequently affected by a severe COVID-19 disease with a higher rate of mortality . Therefore, increasing attention is being directed to analyze the impact of underlying diseases on the prognosis of COVID-19 [24–26]. In particular, cardiac disease represents the most common comorbidity in patients with COVID-19 and it has been demonstrated that CVD can be regarded as a strong risk factor for rapid progression and poor prognosis of COVID-19 .
In a retrospective study of 138 patients from the University of Wuhan, patients who met the need for admission to the intensive care unit were significantly older and had underlying comorbidities more frequently, such as hypertension, diabetes mellitus and known CAD . On the other hand, it is plausible that also the presence of COVID-19 infection may contribute to accelerate the cardiovascular disease progression. The basis of myocardial damage from COVID-19 exists direct damage to myocardiocytes, systemic inflammation, myocardial interstitial fibrosis, exaggerated T-cell Helper Type 1 and 2 activation, coronary plaque destabilization and hypoxia . In our study population the presence of COVID-19 infection and abnormal MPS was associated with the worst prognosis in a follow-up of about two years. Patients with normal MPS and without COVID-19 disease showed the best prognosis. Interestingly, there were no significant difference in outcome between patients with COVID-19 and normal or abnormal MPS. The presence of COVID-19 infection in patients with suspected or known CAD is seems to be decisive in defining the risk of cardiac event. It may be possible that the presence of COVID-19 could be responsible of cardiac disease progression and poor outcome independently of others cardiac risk factors and the presence of abnormal perfusion.
It is well known that Coronaviruses can bind to some metal peptidases such as ACE2, which is present in the epithelial cells of the pulmonary alveoli, epithelial cells of the small intestine, arterial and venous endothelial cells and smooth muscle cells . The variety of expression of ACE2 suggests the correlation between SARS-COVID-2 and extra-pulmonary manifestations, in particular cardiac involvement. COVID-19 through its Spike protein binds strongly to ACE2 receptors and after entering cells, determines a down-regulation of the expression of ACE2, for which the enzyme is no longer able to perform his role. Sars-COVID 2 is therefore able to down regulate the ACE2 pathways at the myocardial and pulmonary level, mediating myocardial inflammation, pulmonary edema and acute respiratory failure . Adult patients affected by CVD, arterial hypertension, diabetes, and/or chronic obstructive pulmonary disease show worse clinical outcome following contraction of the viral illness with fatality rate attaining 10.5% . In addition, the cytokine storm associated to virus infection as an expression of an exaggerated response of the host's immune system, is highly detrimental to the heart. Cardiac complications associated with viral pneumonia include malignant arrhythmias, myocardial infarction, and heart failure . Myocardial damage during COVID-19 can be asymptomatic and therefore can only be evaluated with laboratory markers, or it can be clinically evident. A recent meta-analysis reports how the evolution of COVID-19 disease can exacerbate a pre-existing ventricular dysfunction or predispose to a new cardiomyopathy . Therefore, the presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality. However, on the other hand COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism. Our preliminary results involved a limited number of patients in a short-term follow-up. Probably an analysis in a larger study population followed for more time could help to better elucidate the relationship between COVID-19 infection and cardiovascular disease and to evaluate the correlation between infection and poor outcome. Moreover, it has been demonstrated that COVID-19 induced an endothelial cell dysfunction by an excessive generation of thrombin and a shutdown of fibrinolysis, which indicate a state of hyper-coagulability . Therefore, investigations on microvascular and endothelial damage can play a fundamental role in explaining the pathophysiological mechanisms, the clinical course and for the development of new treatments, as well as to reduce the number of those who will need intensive care units.