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
| COVID-19 positive | COVID-19 negative | P value | |
|---|---|---|---|
| N = 45 | N = 76 | ||
| Demographics | |||
| Male sex—no./total no. (%) | 37/45 (82.2) | 59/76 (77.6) | 0.55 |
| Age (years) | 69.7 ± 11.1 (N = 45) | 65.8 ± 10.7 (N = 76) | 0.06 |
| BMI (kg/m2) | 26.5 ± 3.2 (N = 44) | 27.7 ± 4.9 (N = 74) | 0.11 |
| ACS type | |||
| STE-ACS | 27/45 (60.0) | 43/76 (56.6) | 0.71 |
| NSTE-ACS | 18/45 (40.0) | 33/76 (43.4) | 0.71 |
| Symptoms on admission—no./total no. (%) | |||
| Chest pain | 34/45 (75.6) | 54/71 (76.1) | 0.95 |
| Dyspnea | 23/45 (51.1) | 14/71 (19.7) | < 0.001 |
| Cardiac biomarkers—median (IQR) | |||
| Troponin maximum—factor increase in ULN" | 97.36 (33.44–411.78) N = 43 | 139.46 (17.16–410.14) N = 76 | 0.79 |
| Creatine kinase maximum—factor increase in ULN | 6.55 (1.39–20.96) N = 27 | 4.16 (0.94–10.48) N = 76 | 0.14 |
| BNP maximum—factor increase in ULN$ | 2.56 (0.92–22.26) N = 20 | 4.03 (1.62–11.05) N = 72 | 0.80 |
| Inflammatory markers—median (IQR) | |||
| CRP maximum (mg/l) | 15.20 (7.95–60.68) N = 36 | 26.00 (6.80–62.00) N = 75 | 0.59 |
| WBC maximum (10− 3/µl) | 11.94 (9.44–16.58) N = 44 | 11.16 (8.42–15.56) N = 75 | 0.15 |
| Vital signs—mean ± SD | |||
| Heart rate on admission (beats/min) | 82.4 ± 16.0 (N = 37) | 79.5 ± 15.7 (N = 76) | 0.37 |
| Systolic blood pressure on admission (mmHg) | 131.6 ± 26.6 (N = 45) | 134.0 ± 27.4 (N = 76) | 0.64 |
| Diastolic blood pressure on admission (mmHg) | 78.1 ± 16.1 (N = 45) | 77.9 ± 14.6 (N = 76) | 0.94 |
| LVEF (%) | 42.5 ± 11.4 (N = 43) | 44.7 ± 13.1 (N = 53) | 0.40 |
| ECG on admission | |||
| Sinus rhythm—no./total no. (%) | 41/45 (91.1) | 70/74 (94.6) | 0.48 |
| QTc (ms) | 430.2 ± 28.0 (N = 31) | 435.9 ± 34.5 (N = 74) | 0.42 |
| Cardiovascular risk factors/comorbidities—no./total no. (%) | |||
| Arterial hypertension | 36/45 (80.0) | 39/76 (51.3) | 0.002 |
| Diabetes mellitus | 12/44 (27.3) | 19/76 (25.0) | 0.78 |
| Hypercholesterolemia | 19/45 (42.2) | 42/76 (55.3) | 0.17 |
| Cancer | 2/45 (4.4) | 6/76 (7.9) | 0.71* |
| Cerebrovascular disease | 3/45 (6.7) | 7/76 (9.2) | 0.74* |
| COPD/asthma | 2/45 (4.4) | 7/76 (9.2) | 0.48* |
| Coronary artery disease | 13/45 (28.9) | 22/76 (28.9) | 1.0 |
| Renal disease | 5/45 (11.1) | 10/76 (13.2) | 0.74 |
| Medication on admission—no./total no. (%) | |||
| ACE inhibitor | 15/45 (33.3) | 15/71 (21.1) | 0.14 |
| AT antagonist | 7/45 (15.6) | 20/71 (28.2) | 0.12 |
| Beta-blocker | 16/45 (35.6) | 18/71 (25.4) | 0.24 |
| Calcium-channel antagonist | 8/45 (17.8) | 13/71 (18.3) | 0.94 |
| Statin | 16/45 (35.6) | 29/71 (40.8) | 0.70* |
| Coumarin | 1/45 (2.2) | 4/71 (5.6) | 0.64 |
| Direct oral anticoagulant | 1/45 (2.2) | 1/71 (1.4) | 1.0* |
| COVID-19 specific therapy—no./total no. (%) | |||
| Hydroxychloroquine | 24/45 (53.3) | ||
| Remdesivir | 1/45 (2.2) | ||
| Lopinavir/Ritonavir | 12/45 (26.7) | ||
| Baricitinib | 1/45 (2.2) | ||
| Tocilizumab | 3/45 (6.7) | ||
| Acute cardiac care treatment—no./total no. (%) | |||
| Catecholamine use | 9/37 (24.3) | 12/76 (15.8) | 0.27 |
| Invasive or non-invasive ventilation | 17/45 (37.8) | 12/76 (15.8) | 0.006 |
| Cardiopulmonary resuscitation | 6/37 (16.2) | 13/76 (17.1) | 0.91 |
| In-hospital death—no./total no. (%) | 12/44 (27.3)° | 6/76 (7.9) | 0.004 |
ACE angiotensin converting enzyme, ACS acute coronary syndrome, AT angiotensin, BMI body mass index, BNP brain natriuretic peptide, COPD chronic obstructive pulmonary disease, COVID-19 coronavirus disease 2019, CRP c-reactive protein, ECG electrocardiogram, IQR interquartile range, LVEF left ventricular ejection fraction, NSTE non-ST-segment elevation, QTc QT time corrected for heart rate, SD standard deviation, STE ST-segment elevation, ULN upper limit of the normal, WBC white blood cell count
"Including upper limits of troponin T, high-sensitivity troponin T and troponin I
$Including upper limits of brain natriuretic peptide and the N-terminal of prohormone brain natriuretic peptide
°One patient was still hospitalized at time of performing statistical analysis
*Fisher's exact test
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.
Funding
None.
Compliance with ethical standards
Conflict of interest
The authors report no conflicts of interest.
Footnotes
Victoria L. Cammann, Konrad A. Szawan, Jelena R. Ghadri and Christian Templin contributed equally to this work.
References
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