Sirs:

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a fast spreading disease with high morbidity and mortality [1]. COVID-19 can contribute to severe myocardial injury, ultimately culminating in acute coronary syndromes (ACS) [2]. Clinical features and outcomes of patients with SARS-CoV-2 associated ACS have not been elucidated, yet.

In a multicenter study, COVID-19 positive patients diagnosed with angiographically confirmed ACS between February 19 and April 9 2020 at 17 sites in Italy, Spain, and Switzerland were compared to COVID-19 negative ACS patients from the University Hospital Zurich. In addition, patients with ST-segment elevation (STE)-ACS COVID 19 positive vs. COVID-19 negative were compared as well as patients with non-ST-segment elevation (NSTE)-ACS COVID-19 positive vs. COVID-19 negative.

Out of 4702 patients with COVID-19, 45 (0.96%) had ACS, of which 27 (60.0%) had STE-ACS and 18 (40.0%) NSTE-ACS. Single vessel disease was present in 25 patients (55.6%) of COVID-19 positive ACS and multi vessel disease in 20 patients (44.4%), respectively. All patients received percutaneous coronary intervention.

COVID-19 positive ACS patients were more likely to present with dyspnea (51.1% vs. 19.7%; P < 0.001) and arterial hypertension (80.0% vs. 51.3%; P = 0.002), while other patients’ characteristics were largely comparable to COVID-19 negative ACS patients (Table 1). Of note, in-hospital mortality was more than 3 times higher in COVID-19 positive ACS patients than in COVID-19 negative ACS patients (27.3% vs. 7.9%; P = 0.004, Table 1). Furthermore, when stratifying patients according to the presence or absence of ST-segment elevation, COVID-19 positive patients with STE-ACS had higher mortality rates compared to COVID-19 negative STE-ACS patients (33.3% vs. 9.3%; P = 0.024) and also COVID-19 positive patients with NSTE-ACS showed numerically higher mortality rates compared to COVID-19 negative NSTE-ACS patients (17.6% vs. 6.1%; P = 0.32). Importantly, 9 out of 12 (75%) deceased COVID-19 positive ACS patients had involvement of multiple organ systems in addition to cardiac manifestations, thus indicating a systemic vascular damage. In comparison to recovered COVID-19 positive ACS patients, deceased COVID-19 positive ACS patients had markedly elevated troponin values (factor increase in upper limit of the normal (ULN): 65.00 vs. 323.00; P = 0.014) and brain natriuretic peptide values (factor increase in ULN: 2.00 vs. 113.23; P = 0.023) accompanied by severely depressed left ventricular ejection fraction (45.3 ± 10.3% vs. 34.3 ± 9.5%; P = 0.003) suggesting incremental SARS-CoV-2 related myocardial injury further aggravating ACS related heart failure.

Table 1 Characteristics of ACS Patients
Full size table

The relatively low frequency of ACS in COVID-19 may in part explained by the fact that not all COVID-19 positive patients who exhibit ST-segment elevation undergo coronary angiography [3]. The concomitant occurrence of COVID-19 and ACS might be responsible for the increased mortality. Pathophysiological mechanisms underlying COVID-19 related ACS events are unknown but might include acute plaque rupture or erosion facilitated by systemic inflammation, microvascular thrombosis due to hypercoagulability, and/or endothelial dysfunction [4]. The latter is known to play a key role in arterial hypertension and thrombosis and has recently been associated with COVID-19 [5]. In this respect, endotheliitis in COVID-19 might affect various vascular beds thereby increasing the susceptibility for thromboembolic and septic complications or multi-organ-failure [5]. Thus, myocardial ischemia due to ACS might be even aggravated by COVID-19 induced generalized microvascular dysfunction and systemic vascular damage leading to severe heart failure with unfavorable outcomes. Therefore, in addition to a guideline-directed ACS management, therapies to improve endothelial dysfunction might be considered in patients with COVID-19.