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      Collateral damage of COVID-19-lockdown in Germany: decline of NSTE-ACS admissions

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      Clinical Research in Cardiology
      Springer Berlin Heidelberg

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          Abstract

          Sirs: The SARS-CoV-2-Pandemic reaching Germany in March 2020 led to a nation-wide lockdown with serious restrictions on public life. Based on the experiences of the tsunami-like waves of infections in other European countries, Germany was preparing for a massive load of severe COVID-19-cases by increasing the number of intensive-care-beds and by cancelling the majority of elective medical procedures to provide as many hospital beds as possible. We conducted a retrospective review of ACS-admissions to the Heart Center Ludwigshafen, an academic tertiary heart center in Germany (using ICD-codes I20.0; I21.0, I21.1 and I21.4). We compared the period March 1st to April 21st in 2020 with the same time period in the years 2017–2019 as reference. We did the same analysis for January and February 2017–2020 to show average numbers of ACS cases over the years. During the COVID-19 lockdown in Germany in March/April 2020, we observed unchanged numbers for STEMI-admissions, but a significant 50% reduction in NSTE-ACS, in both UA and NSTEMI (Fig. 1). Similar findings were previously reported in Austria and Italy [1, 2]. Fig. 1 ACS admissions to an academic tertiary heart center before and during the shut-down for the SARS-COV-2-pandemic in Germany. Panel a: Number of treated patients with STEMI, NSTEMI and UA for the periods of January and February 2017 to 2020: Numbers are stable over 4 years. Panel b: Number of treated patients with STEMI, NSTEMI and UA for the periods of March and April (until April 21st) 2017 to 2020: Numbers of NSTEMI and UA drop by 50% in 2020. STEMI ST-elevation-myocardial-infarction, NSTEMI Non-ST-elevation-myocardial-infarction, UA unstable angina We compared patient characteristics of ACS patients during the COVID-lockdown with the same time period of the year 2019 (Table 1). We did not find any relevant differences in the patient characteristics during the COVID-lockdown as compared to the year before. The current data do not provide any indication of who of the ACS population was not admitted to the hospital during the COVID-lockdown. We provide data on troponin values of all NSTEMI patients for the two time periods in 2019 and 2020 in the table. The troponin values reported are the maximal values on the first 2 days after admission for the acute event. The median troponin values during the COVID-lockdown were slightly higher as compared to the values from 2019, but significance was not reached (Table 1). Table 1 Patient characteristics of ACS patients (STEMI, NSTEMI, UA) for the time periods March, 1 to April, 21 2019 compared to March, 1 to April, 21 2020 STEMI NSTEMI UA Time period Mar-Apr 2019 Mar-Apr 2020 p value Mar-Apr 2019 Mar-Apr 2020 p value Mar-Apr 2019 Mar-Apr 2020 p value Number of admissions (n) 49 46 n.s 95 50  < 0.001 94 48  < 0.001  Female gender 26.5% (13/49) 32.6% (15/46) 0.52 27.4% (26/95) 32.0% (16/50) 0.56 38.3% (36/94) 43.8% (21/48) 0.53  Age (years. mean ± SD) 65,9 ± 14,2 64,0 ± 13,8 0.67 70,5 ± 12,3 71,7 ± 12,1 0.58 68.8 ± 13.7 70.5 ± 10.8 0.58 CV risk factors  Art. hypertension 83.7% (41/49) 73.9% (34/46) 0.24 77.9% (74/95) 82.0% (41/50) 0.56 83.0% (78/94) 83.3% (40/48) 0.96  Diabetes mellitus 16.3% (8/49) 34.8% (16/46)  < 0.05 33.7% (32/95) 40.0% (20/50) 0.45 29.8% (28/94) 20.8% (10/48) 0.25  Hyperlipidemia 51.0% (25/49) 65.2% (30/46) 0.16 61.1% (58/95) 74.0% (37/50) 0.12 45.7% (43/94) 66.7% (32/48)  < 0.05  Smoker (current) 22.4% (11/49) 15.2% (7/46) 0.37 9.5% (9/95) 6.0% (3/50) 0.47 7.4% (7/94) 10.4% (5/48) 0.55  Comorbidities 6.1% (3/49) 2.2% (1/46) 0.34 9.5% (9/95) 6.0% (3/50) 0.47 10.6% (10/94) 12.5% (6/48) 0.74  COPD 0.0% (0/49) 2.2% (1/46) 0.30 17.9% (17/95) 14.0% (7/50) 0.55 6.4% (6/94) 4.2% (2/48) 0.59  Peripheral artery disease 2.0% (1/49) 0.0% (0/46) 0.33 1.1% (1/95) 2.0% (1/50) 0.64 0.0% (0/94) 0.0% (0/48) n.a  Prior stroke/TIA 16.3% (8/49) 13.0% (6/46) 0.65 42.1% (40/95) 36.0% (18/50) 0.48 20.2% (19/94) 18.8% (9/48) 0.84  Renal failure 6.1% (3/49) 2.2% (1/46) 0.34 9.5% (9/95) 6.0% (3/50) 0.47 10.6% (10/94) 12.5% (6/48) 0.74  Troponin I hs (ng/l)Median with interquartile range n.a n.a n.a 1179,0 (294,0; 5660,0) 1501,0 (530,0; 8788,0) 0.27 n.a n.a n.a STEMI ST-elevation-myocardial-infarction, NSTEMI Non-ST-elevation-myocardial-infarction, UA unstable angina Statistical Analysis: Continuous variables are presented as mean with standard deviation or median with interquartile range and compared with Mann–Whitney-Wilcoxon test. Categorical variables are presented as counts and percentages and compared with the Chi2-test. All tests were two-tailed and p values < 0.05 were considered statistically significant. Statistical analyses were performed with SAS statistical package, version 9.4 (SAS Institute) Possible explanations for this important observation might be system-related as well as patient-related. By concentrating on the preparation for the COVID-19-pandemic with all necessary efforts undertaken to care for the isolation and treatment of suspected or confirmed cases, established integrated care systems for other acute diseases with well-defined patient pathways might have been neglected. Besides, the lockdown isolated many patients at risk for cardiovascular events and the quarantine of patients with suspected or confirmed SARS-CoV-2-infection at home sometimes might have prevented them from contacting their doctors. The acute presentation of STEMI with severe chest-pain probably still triggers the direct transportation to the cathlabs with no changes of admissions. Due to the attention to the plethora of possible symptoms of the SARS-CoV-2-infection described in the media, some patients may have mis-interpreted their NSTE-ACS symptoms such as dyspnea and chest pain as possible COVID-19-symptoms rather than as cardiovascular symptoms. As an early invasive treatment of NSTEMI-patients is associated with an improved outcome [3, 4], we might face a higher mortality by non-treated ACS patients as a collateral damage of the COVID-19-era. We, therefore, should take care about reinforcing the already established patient pathways ensuring the access to emergency cardiology care of those patients separated from the access to hospital care for COVID-19-infections that will continue to accompany us in the future until an effective vaccine is developed, to avoid undertreatment of NSTE-ACS-patients.

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          Reduced Rate of Hospital Admissions for ACS during Covid-19 Outbreak in Northern Italy

          To the Editor: To address the coronavirus (Covid-19) pandemic, 1 strict social containment measures have been adopted worldwide, and health care systems have been reorganized to cope with the enormous increase in the numbers of acutely ill patients. 2,3 During this same period, some changes in the pattern of hospital admissions for other conditions have been noted. The aim of the present analysis is to investigate the rate of hospital admissions for acute coronary syndrome (ACS) during the early days of the Covid-19 outbreak. In this study, we performed a retrospective analysis of clinical and angiographic characteristics of consecutive patients who were admitted for ACS at 15 hospitals in northern Italy. All the hospitals were hubs of local networks for treatment involving primary percutaneous coronary intervention. The study period was defined as the time between the first confirmed case of Covid-19 in Italy (February 20, 2020) and March 31, 2020. We compared hospitalization rates between the study period and two control periods: a corresponding period during the previous year (February 20 to March 31, 2019) and an earlier period during the same year (January 1 to February 19, 2020). The primary outcome was the overall rate of hospital admissions for ACS. We calculated incidence rates for the primary outcome by dividing the number of cumulative admissions by the number of days for each time period. Incidence rate ratios comparing the study period with each of the control periods were calculated with the use of Poisson regression. (Details regarding the study methods are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.) Of the 547 patients who were hospitalized for ACS during the study period, 420 (76.8%) were males; the mean (±SD) age was 68±12 years. Of these patients, 248 (45.3%) presented with ST-segment elevation myocardial infarction (STEMI). The mean admission rate for ACS during the study period was 13.3 admissions per day. This rate was significantly lower than either the rate during the earlier period in the same year (total number of admissions, 899; 18.0 admissions per day; incidence rate ratio, 0.74; 95% confidence interval [CI], 0.66 to 0.82; P<0.001) or the rate during the previous year (total number of admissions, 756; 18.9 admissions per day; incidence rate ratio, 0.70; 95% CI, 0.63 to 0.78; P<0.001). The incidence rate ratios for individual ACS subtypes are presented in Table 1. After the national lockdown was implemented on March 8, 2020, 4 a further reduction in ACS admissions was reported. (Details regarding the full secondary analyses are provided in the Supplementary Appendix.) This report shows a significant decrease in ACS-related hospitalization rates across several cardiovascular centers in northern Italy during the early days of the Covid-19 outbreak. Recent data suggest a significant increase in mortality during this period that was not fully explained by Covid-19 cases alone. 5 This observation and data from our study raise the question of whether some patients have died from ACS without seeking medical attention during the Covid-19 pandemic.
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            Decline of acute coronary syndrome admissions in Austria since the outbreak of COVID-19: the pandemic response causes cardiac collateral damage

            We conducted a nationwide retrospective survey on the impact of COVID-19 on the diagnosis and treatment of acute cornary syndrome (ACS) from 2 to 29 March in Austria. Of the 19 public primary percutaneous coronary (PCI) centres contacted, 17 (90%) provided the number of admitted patients. During the study period, we observed a significant decline in the number of patients admitted to hospital due to ACS (Figure 1 ). Comparing the first and last calendar week, there was a relative reduction of 39.4% in admissions for ACS. In detail, from calendar week 10 to calendar week 13, the number of ST-segment elevation myocardial infarction (STEMI) patients admitted to all hospitals was 94, 101, 89, and 70, respectively. The number of non-STEMI patients declined even more markedly from 132 to 110, to 62, and to 67. Figure 1 Decline of acute coronary syndrome admissions in Austria since the outbreak of COVID-19. The absolute numbers of all ACS (blue bars), STEMI (orange bars), and NSTEMI (grey bars) admissions in Austria from calendar week 10 to calendar week 13 are shown. Abbreviations: STEMI, ST-segment elevation myocardial infarction; NSTEMI, non-ST-segment elevation myocardial infarction. The main finding of our retrospective observational study is an unexpected major decline in hospital admissions and thus treatment for all subtypes of ACS with the beginning of the COVID-19 outbreak in Austria and subsequent large-scale public health measures such as social distancing, self-isolation, and quarantining. Several factors might explain this important observation. The rigorous public health measures, which are undoubtedly critical for controlling the COVID-19 pandemic, may unintentionally affect established integrated care systems. Amongst others, patient-related factors could mean that infarct-related symptoms such as chest discomfort and dyspnoea could be misinterpreted as being related to an acute respiratory infection. Moreover, the strict instructions to stay at home as well as the fear of infection in a medical facility may have further prevented patients with an ACS from going to a hospital. Irrespective of the causes, the lower rate of admitted and therefore treated patients with ACS is worrisome and we are concerned that this might be accompanied by a substantial increase in early and late infarct-related morbidity and mortality. Our study does not provide data on mortality; however, considering the annual incidence of ACS in Austria (200/100 000/year = 17 600/year in 8.8 million habitants) 1 and taking into consideration sudden cardiac deaths and silent infarctions (one-third), there will remain ∼1000 ACS cases a month. The difference between the assumed number of ACS patients and the observed number in our study, i.e. 725 ACS patients in calendar weeks 10–13 is 275. According to these assumptions, 275 patients were not treated in March 2020. Based on data showing that the cardiovascular mortality of untreated ACS patients might be as high as 40% (as it was in the 1950s), 2 we can theoretically estimate 110 ACS deaths during this time frame. The number of deaths associated with this unintentional undersupply of guideline-directed ACS management is very alarming, particularly when considering that the official number of COVID-related deaths in Austria was 86 on 29 March. In conclusion, it seems likely that the COVID-19 outbreak is associated with a significantly lower rate of hospital admissions and thus, albeit unintended, treatment of ACS patients, which is most likely explained by several patient- and system-related factors. Every effort should be undertaken by the cardiology community to minimize the possible cardiac collateral damage caused by COVID-19.
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              Long-term outcome of a routine versus selective invasive strategy in patients with non-ST-segment elevation acute coronary syndrome a meta-analysis of individual patient data.

              This study was designed to determine: 1) whether a routine invasive (RI) strategy reduces the long-term frequency of cardiovascular death or nonfatal myocardial infarction (MI) using a meta-analysis of individual patient data from all randomized studies with 5-year outcomes; and 2) whether the results are influenced by baseline risk. Pooled analyses of randomized trials show early benefit of routine intervention, but long-term results are inconsistent. The differences may reflect differing trial design, adjunctive therapies, and/or limited power. This meta-analysis (n = 5,467 patients) is designed to determine whether outcomes are improved despite trial differences. Individual patient data, with 5-year outcomes, were obtained from FRISC-II (Fragmin and Fast Revascularization during Instability in Coronary Artery Disease), ICTUS (Invasive Versus Conservative Treatment in Unstable Coronary Syndromes), and RITA-3 (Randomized Trial of a Conservative Treatment Strategy Versus an Interventional Treatment Strategy in Patients with Unstable Angina) trials for a collaborative meta-analysis. A Cox regression analysis was used for a multivariable risk model, and a simplified integer model was derived. Over 5 years, 14.7% (389 of 2,721) of patients randomized to an RI strategy experienced cardiovascular death or nonfatal MI versus 17.9% (475 of 2,746) in the selective invasive (SI) strategy (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.71 to 0.93; p = 0.002). The most marked treatment effect was on MI (10.0% RI strategy vs. 12.9% SI strategy), and there were consistent trends for cardiovascular deaths (HR: 0.83, 95% CI: 0.68 to 1.01; p = 0.068) and all deaths (HR: 0.90, 95% CI: 0.77 to 1.05). There were 2.0% to 3.8% absolute reductions in cardiovascular death or MI in the low- and intermediate-risk groups and an 11.1% absolute risk reduction in highest-risk patients. An RI strategy reduces long-term rates of cardiovascular death or MI and the largest absolute effect in seen in higher-risk patients.
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                Author and article information

                Contributors
                gitta@klilu.de
                Journal
                Clin Res Cardiol
                Clin Res Cardiol
                Clinical Research in Cardiology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                1861-0684
                1861-0692
                10 July 2020
                : 1-3
                Affiliations
                Med. Klinik B, Department of Cardiology, Herzzentrum Ludwigshafen, Ludwigshafen, Germany
                Author information
                http://orcid.org/0000-0003-2573-7239
                Article
                1705
                10.1007/s00392-020-01705-x
                7351542
                32651656
                b6d58df9-659b-4004-ac2c-56a824a1c633
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 4 May 2020
                : 1 July 2020
                Categories
                Letter to the Editors

                Cardiovascular Medicine
                Cardiovascular Medicine

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