key: cord-0719409-gpd5sq8g authors: Kite, Thomas A.; Ludman, Peter F.; Gale, Chris P.; Wu, Jianhua; Caixeta, Adriano; Mansourati, Jacques; Sabate, Manel; Jimenez-Quevedo, Pilar; Candilio, Luciano; Sadeghipour, Parham; Iniesta, Angel M.; Hoole, Stephen P.; Palmer, Nick; Ariza-Solé, Albert; Namitokov, Alim; Escutia-Cuevas, Hector H.; Vincent, Flavien; Tica, Otilia; Ngunga, Mzee; Meray, Imad; Morrow, Andrew; Arefin, Md Minhaj; Lindsay, Steven; Kazamel, Ghada; Sharma, Vinoda; Saad, Aly; Sinagra, Gianfranco; Sanchez, Federico Ariel; Roik, Marek; Savonitto, Stefano; Vavlukis, Marija; Sangaraju, Shankar; Malik, Iqbal S.; Kean, Sharon; Curzen, Nick; Berry, Colin; Stone, Gregg W.; Gersh, Bernard J.; Gershlick, Anthony H. title: International Prospective Registry of Acute Coronary Syndromes in Patients With COVID-19 date: 2021-05-25 journal: J Am Coll Cardiol DOI: 10.1016/j.jacc.2021.03.309 sha: 696f96be9119394518a94e967b90eaeed96d93d1 doc_id: 719409 cord_uid: gpd5sq8g BACKGROUND: Published data suggest worse outcomes in acute coronary syndrome (ACS) patients and concurrent coronavirus disease 2019 (COVID-19) infection. Mechanisms remain unclear. OBJECTIVES: The purpose of this study was to report the demographics, angiographic findings, and in-hospital outcomes of COVID-19 ACS patients and compare these with pre–COVID-19 cohorts. METHODS: From March 1, 2020 to July 31, 2020, data from 55 international centers were entered into a prospective, COVID-ACS Registry. Patients were COVID-19 positive (or had a high index of clinical suspicion) and underwent invasive coronary angiography for suspected ACS. Outcomes were in-hospital major cardiovascular events (all-cause mortality, re–myocardial infarction, heart failure, stroke, unplanned revascularization, or stent thrombosis). Results were compared with national pre–COVID-19 databases (MINAP [Myocardial Ischaemia National Audit Project] 2019 and BCIS [British Cardiovascular Intervention Society] 2018 to 2019). RESULTS: In 144 ST-segment elevation myocardial infarction (STEMI) and 121 non–ST-segment elevation acute coronary syndrome (NSTE-ACS) patients, symptom-to-admission times were significantly prolonged (COVID-STEMI vs. BCIS: median 339.0 min vs. 173.0 min; p < 0.001; COVID NSTE-ACS vs. MINAP: 417.0 min vs. 295.0 min; p = 0.012). Mortality in COVID-ACS patients was significantly higher than BCIS/MINAP control subjects in both subgroups (COVID-STEMI: 22.9% vs. 5.7%; p < 0.001; COVID NSTE-ACS: 6.6% vs. 1.2%; p < 0.001), which remained following multivariate propensity analysis adjusting for comorbidities (STEMI subgroup odds ratio: 3.33 [95% confidence interval: 2.04 to 5.42]). Cardiogenic shock occurred in 20.1% of COVID-STEMI patients versus 8.7% of BCIS patients (p < 0.001). CONCLUSIONS: In this multicenter international registry, COVID-19–positive ACS patients presented later and had increased in-hospital mortality compared with a pre–COVID-19 ACS population. Excessive rates of and mortality from cardiogenic shock were major contributors to the worse outcomes in COVID-19 positive STEMI patients. S ince its outbreak in Hubei Province, China in December 2019, the novel severe acute respiratory syndrome coronavirus 2 has spread rapidly, resulting in a worldwide pandemic from this multisystem disease (1) . The effect on ACS is 2fold. First, viral infections such as influenza have been reported to exacerbate ACS (2) . Multiple hypotheses for the higher incidence and greater adverse outcomes in ACS have been proposed, including arterial (macrovascular and microvascular) and venous thrombosis mediated by an endothelial inflammatory response, microvascular dysfunction, sepsis hypoxia, sympathetic nervous system overactivity, and cytokine and possible bradykinin release (3) . Indeed, early reports suggest spontaneous thrombus development in the pulmonary and peripheral vasculature (4) and excess coronary thrombus formation may be causes for high mortality rates (5) . However, nonobstructed epicardial coronary arteries with microthrombi or cellular inflammatory processes have also been observed (6) , as have cases of myocarditis masquerading as ACS (7) . Values are mean AE SD or % (n/N). Denominators not equal to n ¼ 265 are due to incomplete data. *Excludes patients with type 2 myocardial infarction (see Figure 1 ). In total, 316 hospitalized patients from 55 international centers across 5 continents were included: 238 (75.3%) from Europe, 35 (11.1%) from South America, 21 (6.6%) from Asia, 15 (4.7%) from Africa, and 7 (2.2%) from North America (Supplemental Table 1 ). Demographic variables and comorbidities for the combined STEMI/NSTE-ACS cohort are shown in Table 1 . data. The study profile is outlined in Figure 1 . Demographics, comorbidities, procedural characteristics, and post-procedural support requirements in the COVID-STEMI subgroup are shown in Table 2 . Compared with non-COVID STEMI patients (BCIS Abbreviations as in Tables 1 and 2 . Similarly, in the COVID NSTE-ACS subgroup, symptom onset to admission times were prolonged, and admission systolic blood pressure was lower. However, no significant delays in admission to angi- This international registry describes the demographics, procedural characteristics, and outcomes of COVID-19 ACS patients undergoing invasive coronary angiography and compares these to Abbreviations as in Table 1 . Abbreviations as in Table 1 . Kite et al. Our study focused on COVID-19-positive ACS cases, including time to treatment and potential mechanisms driving the elevated mortality rates in these patients. Symptom-to-admission times and STEMI door-toballoon times in our registry were significantly greater than the pre-COVID cohort and should be considered in the context of decreases in absolute hospitalizations for ACS during the COVID-19 pandemic (8,10,21)-most likely due to public fear of viral contagion (22) . We assert that the delays seen in door-to-balloon time data may be due to restructured "COVID-19 pathways" and time spent donning appropriate PPE, which was utilized in more than 90% of cases from our registry. The nonsignificant trend to accelerated door-to-angiography times in our NSTE-ACS group is likely due to widespread suspension of elective catheter laboratory work (23), thus creating availability for acute cases. Our data support the notion that prolonged ischemia times were associated with poor outcomes, with a 10% increase in mortality for the COVID-ACS patients for every 10-min delay. This was exacer- Given the strong relationship between prolonged ischemia time and poorer outcomes in STEMI, the increased incidence of CGS is an important contributor to the higher rates of adverse outcomes and supports reported data of excess deaths due to CGS during the pandemic (22) . Historical ACS longitudinal data describe the incidence of CGS as approximately 7% (24), one-half of the 13.2% in our study. The relationship of presentation times and onset of CGS is intuitive, but is not robustly reported. It is therefore reasonable to assert that prolonged ischemia times in our population were responsible for the high incidence of CGS, although consideration must be given to the hypothesis that higher CGS incidence could also be related to COVID-19 infection and potential pro-thrombotic mechanisms. Values are % (n/N) or median (interquartile range). *n ¼ 19, n ¼ 106 due to incomplete data. CGS ¼ cardiogenic shock; IQR ¼ interquartile range; other abbreviations as in Table 1 . Values are odds ratio (95% confidence interval). COVID-STEMI and BCIS were matched for age, sex, hypertension, diabetes, and hyperlipidemia using a propensity score. Total ischemic time (symptom-to-admission plus admission-to-balloon) was right skewed, therefore a logarithm transformation with base 10 was performed. *Overall mortality: this adjusts for age, sex, hypertension, hyperlipidemia, diabetes, ischemia time, and CGS. †Mortality related to ischemia time. ‡Mortality related to presence of CGS. Abbreviations as in Tables 1 and 6 . Ischaemia National Audit Project (MINAP) databases, patients enrolled in the International COVID-ACS registry were found to experience significant delays in presentation to hospital and time to reperfusion therapy, excess rates of cardiogenic shock, and greater in-hospital mortality. These novel data suggest 1 potential mechanism for the poorer outcomes observed in patients with acute coronary syndrome (ACS) and COVID- 19 , and yet again support is associated with a poor prognosis, particularly when medical intervention is delayed. TRANSLATIONAL OUTLOOK: More research is needed to elucidate the mechanisms that trigger acute coronary syndromes in patients with COVID-19, their impact on the incidence and outcomes of cardiogenic shock, and implications for management. 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