Transient ST-segment elevation in coronavirus disease-2019

Cardiovascular involvement in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections may contribute to morbidity and mortality.1 Acute myocardial injury, defined by increased high-sensitivity troponin I (hs-TnI) levels, is the most common finding.2,3 Clinical phenotypes associated with high levels of hs-TnI include myocarditis, arrhythmias, acute coronary syndromes (ACS) and heart failure.2,4 The underlying pathogenetic mechanisms are still unclear. Early reports suggest cytokine storm and widespread endothelial damage as the most relevant causes5 but conflicting data emerged from clinical and pathology studies. Contributing to the interpretation of available evidence, we describe two cases of transient ST-segment elevation and mild increase in hs-TnI of probable vasospastic etiology in laboratory-confirmed coronavirus disease-2019 (COVID-19). Case 1: A 59-year-old man with hypertension and history of catheter ablation for atrial fibrillation was admitted for SARS-CoV-2 pneumonia. He was treated with invasive mechanical ventilation, inotropes, antivirals and low-molecular-weight heparin (LMWH). In the morning of day 16, the patient reported acute oppressive chest pain and dyspnea. An ECG recorded at 8 : 19 a.m. showed ST-segment elevation in the inferior and anterior leads (Fig. 1a). Pain relief and ECG normalization occurred at 8 : 51 am, upon arrival in the Cath lab (Fig. 1b). Angiography showed normal coronary arteries (Fig. 1c and d). Arterial blood gas analysis was normal and hs-TnI levels increased from 25.3 to 1162.9 ng/l. Transthoracic echocardiography and thrombophilia screening showed no alterations.Fig. 1: Electrocardiographic and angiographic findings. Top panels refer to case 1 whereas bottom panels refer to case 2. Panels a and e report the electrocardiograms during chest pain and panels b and f after its regression. Panels c and g show angiographic views of the right coronary arteries whereas panels d and h show the left coronary arteries. In case 1, the coronary arteries have a normal angiographic appearance; in case 2, nonsignificant atheromatous plaques are visible. No endoluminal thrombi are observed in both cases.On day 19, after a negative nasopharyngeal swab for SARS-CoV-2, a provocative spasm test by hyperventilation was performed without eliciting symptoms or ECG changes. The following day, the patient was discharged on diltiazem. Case 2: A 78-year-old woman with hypertension, dyslipidemia and history of heart failure with preserved ejection fraction was admitted for decompensated heart failure on rapid atrial fibrillation. She was treated with beta-blockers, diuretics and LMWH. Despite noninvasive mechanical ventilation and atrial fibrillation spontaneous cardioversion, dyspnea did not improve. As her husband had died a month earlier from COVID-19, a nasopharyngeal swab was performed, which tested positive. The following day in the evening, the patient reported sudden onset of chest pain. An ECG recorded at 6 : 22 p.m. showed marked ST-segment elevation in the inferior and anterior leads (Fig. 1e). Intravenous nitrates were promptly administered with symptom regression within a few minutes. Just before transfer to the Cath lab, the ECG recorded at 6 : 28 p.m. returned to the baseline (Fig. 1f). Angiography showed patent coronary arteries (Fig. 1g and h). Hs-TnI increased to 142.1 ng/l. Echocardiographic findings were unremarkable. During the night, frequent runs of nonsustained polymorphic ventricular tachycardia occurred and were treated with intravenous lidocaine (Figure S1, https://links.lww.com/JCM/A309). At 2 : 06 a.m., ventricular fibrillation was detected and immediately treated with effective DC-shock, but it relapsed within a few minutes (Figure S2, https://links.lww.com/JCM/A309). The patient went into arrhythmic storm refractory to DC-shocks and resuscitation maneuvers. Over a third of COVID-19 patients with ST-segment elevation have nonobstructive coronary disease.6,7 Probable causes are type-2 MI, myocarditis, coronary spasm, microthrombi, or direct endothelial or vascular injury. Except for a few case reports of myocarditis during SARS-CoV-2 infection,8,9 no clinical evidence is available to confirm those pathogenetic mechanisms. In our cases, the transient nature of symptoms and ECG changes, the mild troponin elevation and the absence of obstructive coronary disease or any endoluminal thrombotic material support the hypothesis that coronary artery spasm is a relevant cause of myocardial injury and ECG changes induced by SARS-CoV-2. Coronary endothelium is particularly susceptible to SARS-CoV-2 infection as endothelial cells and pericytes highly express the viral functional receptor angiotensin-converting enzyme 2 (ACE2)10 and evidence of direct endothelial infection has been reported.11 In this context, the reduced expression of constitutive endothelial nitric oxide synthetase and the release of prostacyclins counterbalance the normal vasodilatory properties of the endothelium favoring a pro-thrombotic state with platelet activation and release of powerful vasoconstrictors, such as thromboxane A2 and serotonin. Those effects can be enhanced by inflammatory-induced release of endogenous catecholamines. Indeed, myocardial inflammation is associated with endothelial dysfunction of systemic arteries12 and coronary vasospasm could be elicited in 70% of patients with immunohistological documentation of viral myocarditis.13 Furthermore, SARS-CoV-2-induced ACE2 down-regulation increases the plasmatic concentration of angiotensin II, a peptide responsible for vasoconstriction and endothelial dysfunction, which cannot be offset by the production of Angiotensin 1–7, a potent coronary vasodilator, by ACE2 cleavage. Despite the strong biological plausibility, the clinical relevance and real-world incidence of these events have yet to be established. Acknowledgements We thank all the health staff of the Cardiology Department of the Crema Hospital. Special thanks also to Prof. Eloisa Arbustini for her valuable advice. Conflicts of interest There are no conflicts of interest.