Indirect impact of the COVID-19 pandemic on hospitalisations for cardiometabolic conditions and their management: A systematic review

  • Samuel Seidu
    Correspondence
    Corresponding author at: Leicester Real World Evidence Unit, Diabetes Research Centre, Leicester General Hospital, Gwendolen Rd, Leicester LE5 4PW, UK.
    Affiliations
    Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, UK
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  • Setor K. Kunutsor
    Affiliations
    National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol, Bristol, UK

    Musculoskeletal Research Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Learning & Research Building (Level 1), Southmead Hospital, Bristol, BS10 5NB, UK
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  • Xavier Cos
    Affiliations
    DAP_Cat Research Group, Gerencia Territorial Barcelona Ciutat, Institut Català de la Salut, Foundation University Institute for Primary Health Care Research Jordi Gol i Gurina (IDIAPJGol), Barcelona, Spain
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  • Kamlesh Khunti
    Affiliations
    Leicester Real World Evidence Unit, Diabetes Research Centre, University of Leicester, UK
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      Highlights

      • About 89% of studies reported a decline in hospitalisations for cardiovascular diseases during the pandemic.
      • Severe presentation, less use of cardiovascular procedures and longer delays were common during the pandemic.
      • Most studies reported no change in in-hospital mortality among hospitalised patients.
      • Further restructuring needs to be done to maintain high standards of care and prepare for future pandemics.

      Abstract

      Background

      The Coronavirus disease 2019 (COVID-19) pandemic has led to a dramatic crisis in health care systems worldwide. These may have significant implications for the management of cardiometabolic diseases. We conducted a systematic review of published evidence to assess the indirect impact of the COVID-19 pandemic on hospitalisations for cardiovascular diseases and their management.

      Methods

      Studies that evaluated volume of hospitalisations for cardiometabolic conditions and their management with comparisons between the COVID-19 and pre-COVID periods were identified from MEDLINE, Embase and the reference list of relevant studies from January 2020 to 25 February 2021.

      Results

      We identified 103 observational studies, with most studies assessing hospitalisations for acute cardiovascular conditions such as acute coronary syndrome, ischemic strokes and heart failure. About 89% of studies reported a decline in hospitalisations during the pandemic compared to pre-pandemic times, with reductions ranging from 20.2 to 73%. Severe presentation, less utilization of cardiovascular procedures, and longer patient- and healthcare-related delays were common during the pandemic. Most studies reported shorter length of hospital stay during the pandemic than before the pandemic (1–8 vs 2–12 days) or no difference in length of stay. Most studies reported no change in in-hospital mortality among hospitalised patients.

      Conclusion

      Clinical care of patients for acute cardiovascular conditions, their management and outcomes have been adversely impacted by the COVID-19 pandemic. Patients should be educated via population-wide approaches on the need for timely medical contact and health systems should put strategies in place to provide timely care to patients at high risk.

      Systematic review registration

      PROSPERO 2021: CRD42021236102

      Keywords

      1. Introduction

      Coronavirus disease 2019 (COVID-19), a respiratory infectious disease caused severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), was declared a global public health emergency on 30 January 2020 and it has since caused so much morbidity and mortality [
      • Zhou F.
      • Yu T.
      • Du R.
      • Fan G.
      • Liu Y.
      • Liu Z.
      • et al.
      Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
      ]. The COVID-19 virus spreads primarily through droplets generated when an infected person coughs or sneezes, or through droplets of saliva or discharge from the nose. The majority of patients with COVID-19 are asymptomatic or exhibit mild symptoms and never require hospitalisation [
      • Wu Z.
      • McGoogan J.
      Characteristics of and important lessons from the 367 coronavirus disease 2019 (COVID-19) outbreak in China: summary of a report of 368 72314 cases from the Chinese Center for Disease Control and Prevention.
      ], with a few progressing to severe illness with extrapulmonary manifestations, leading to multiorgan failure and death [
      • Kunutsor S.K.
      • Laukkanen J.A.
      Renal complications in COVID-19: a systematic review and meta-analysis.
      ,
      • Kunutsor S.K.
      • Laukkanen J.A.
      Cardiovascular complications in COVID-19: a systematic review and meta-analysis.
      ,
      • Kunutsor S.K.
      • Laukkanen J.A.
      Hepatic manifestations and complications of COVID-19: a systematic review and meta-analysis.
      ,
      • Li Q.
      • Guan X.
      • Wu P.
      • Wang X.
      • Zhou L.
      • Tong Y.
      • et al.
      Early transmission dynamics in Wuhan, China, of novel coronavirus–infected pneumonia.
      ]. Accumulating evidence suggests that older and obese patients, males, Black, Asian and Minority Ethnic groups and those with pre-existing comorbidities such as cardiovascular disease (CVD), hypertension, chronic kidney and liver diseases and diabetes are more likely to be infected with SARS CoV-2 and are at highest risk for severe illness or death from COVID-19 [
      • Kunutsor S.K.
      • Laukkanen J.A.
      Markers of liver injury and clinical outcomes in COVID-19 patients: a systematic review and meta-analysis.
      ,
      • Seidu S.
      • Gillies C.
      • Zaccardi F.
      • Kunutsor S.K.
      • Hartmann‐Boyce J.
      • Yates T.
      • et al.
      The impact of obesity on severe disease and mortality in people with SARS-CoV-2: a systematic review and meta-analysis.
      ,
      • Weiss P.
      • Murdoch D.R.
      Clinical course and mortality risk of severe COVID-19.
      ].
      Several public health response strategies have been introduced to prevent or slow down the transmission of COVID-19 and these include social distancing, quarantine, use of personal protective equipment, and personal hygiene. Since the World Health Organization (WHO) declared COVID-19 a pandemic on 12 March 2020, other strategies introduced to mitigate the spread of the virus have included shutting down entire cities or communities (“lockdowns”) and banning international or domestic travel. During the period of March 2020, most countries all over the world announced nationwide lockdowns, which severely restricted movement among citizens, though people were still allowed to leave their homes for essential reasons, including seeking medical care.
      The COVID-19 pandemic has led to a dramatic crisis of health care systems worldwide directly or indirectly. In pre-pandemic times, large proportions of health service budgets of countries were spent treating chronic health conditions such as CVD, diabetes and their complications. With the pandemic, large proportions of health budgets have been earmarked for COVID-19 management. Healthcare systems have also reorganised their management pathways for acute cardiovascular conditions such as stroke and acute coronary syndromes (ACSs). In addition, the social isolation measures put in place have led to losses in employment and income [
      • Weiss P.
      • Murdoch D.R.
      Clinical course and mortality risk of severe COVID-19.
      ], with changes in human behaviour, including being house-bound and physically inactive because of fear of contracting the virus. All these factors are likely to increase the incidence of cardiometabolic conditions, cause delays in seeking medical care and also adversely affect in-hospital management of these patients. However, a comprehensive synthesis of the evidence of these likely trends is non-existent.
      In this context, using a systematic review of all available published observational evidence, our primary aim was to assess the indirect impact of COVID-19 on hospitalisations (including emergency room attendance) and management for cardiovascular conditions. Our specific objectives were to (i) assess the different cardiometabolic conditions that have been impacted by the COVID-19 pandemic; (ii) assess prevalence and trends in hospitalisations for these cardiovascular conditions as a result of the COVID-19 pandemic; (iii) assess COVID-19 related reasons provided by patients for delaying medical contact; and (iv) assess if in-hospital management of these patients has been affected. We also sought to explore if there are gaps in the existing evidence.

      2. Methods

      2.1 Eligibility criteria

      The review was conducted based on a predefined protocol and in accordance with PRISMA and MOOSE guidelines [
      • Stroup D.F.
      • Berlin J.A.
      • Morton S.C.
      • Olkin I.
      • Williamson G.D.
      • Rennie D.
      • et al.
      Meta-analysis of observational studies in epidemiology: a proposal for reporting.
      ,
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      • Prisma Group
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      ] (Supplementary Appendix 1–2). The protocol has been registered in the PROSPERO prospective register of systematic reviews (CRD42021236102). We searched for clinical observational studies (prospective cohort, retrospective cohort, case-cohort, nested case-control, case-control and cross-sectional) that have evaluated the indirect impact of COVID-19 on hospitalisations (including emergency room attendances) for cardiovascular diseases and management of these conditions. We included studies that reported comparisons between the COVID-19 pandemic period vs. pre-pandemic and/or historical periods (or other comparisons such as lockdown vs pre-lockdown and/or pre-COVID-19 periods; post-pandemic declaration vs pre-pandemic declaration; or in temporal relation to COVID-19 related restrictions). Henceforth, this is referred to as pandemic vs. pre-pandemic period. Cardiovascular conditions included myocardial infarction (MI), ACS (ST-elevation MI (STEMI), non-ST segment elevation MI (NSTEMI) or angina), stroke and acute heart failure (HF); hypertension; venous thromboembolism (VTE); diabetes and related complications; and mortality. The following exclusions were applied: (i) randomised control trials (RCTs); (ii) studies in which patients were selected and matched between the pandemic and pre-pandemic periods; (iii) studies that had evaluated the direct effects of COVID-19 on cardiovascular conditions and their related complications; and (iv) studies with no pre-pandemic controls for comparison or did not evaluate outcomes in temporal relation to COVID-19 related restrictions.

      2.2 Data sources and search strategy

      We searched MEDLINE and Embase from January 2020 to 25 February 2021. The computer-based searches combined free and MeSH search terms related to impact (e.g., “impact”, “effect”, “delay”, “reduction”), COVID-19 (e.g., “COVID-19”, “SARS-CoV-2”) and cardiometabolic condition (e.g., “diabetes”, “myocardial infarction”, “acute coronary syndrome”, “cardiac arrest”, “stroke”, “heart failure”). There were no restrictions on language. Titles and abstracts of retrieved citations were initially screened by one author (SKK) to assess their suitability for potential inclusion, followed by the acquisition of full texts for detailed evaluation. Full-text evaluation was independently conducted by two authors (SKK and SS). Reference lists of retrieved articles were manually scanned for all relevant additional studies and review articles missed by the original search. Citing references were also checked in Web of Science. Full details on the search strategy are presented in Supplementary Appendix 3.

      2.3 Data extraction and risk of bias assessment

      One author (S.K.K.) independently extracted data and performed risk of bias assessments using a standardized predesigned data collection form. A second reviewer (S.S.) checked extracted data with that in the original articles. Data were extracted on publication year, study design, geographical location, pandemic and pre-pandemic periods evaluated, baseline age, proportion of males, cardiometabolic condition and/or related complication, number of hospitalisations for outcome during pandemic and pre-pandemic periods or similar frame, trends in the number of hospitalisations, severity of presentation on hospitalisation, in-hospital management, patient- and system-related delays, COVID-19 related reasons provided for delaying medical contact, length of hospital stay, and outcomes related to in-hospital management. Methodological quality of observational cohort studies was assessed using the nine-star Newcastle–Ottawa Scale (NOS) [
      • Wells G.A.
      • Shea B.
      • O’Connell D.
      • Peterson J.
      • Welch V.
      • Losos M.
      • et al.
      The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised Studies in Meta-Analyses.
      ], which uses pre-defined criteria namely: selection (population representativeness), comparability (adjustment for confounders), and ascertainment of outcome. Nine points on the NOS reflects the highest study quality. For cross-sectional studies, methodological quality was evaluated using the NOS modified for cross-sectional studies [
      • Kunutsor S.K.
      • Apekey T.A.
      • Laukkanen J.A.
      Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence.
      ] (Supplementary Appendix 4). It uses three pre-defined domains namely: selection of participants (population representativeness), comparability (adjustment for confounders), and ascertainment of outcomes of interest. A maximum score of 8 reflected the highest study quality.

      2.4 Data synthesis

      Where possible and appropriate, percentages were calculated [(n/N)*100], where n denotes number of a particular condition and N refers to the total number of conditions. Pooled analysis could not be conducted for any of the outcomes because of the heterogeneous nature of the data. All studies reported trends in hospitalisations and provided data on outcomes, so these were summarised in tables and narrative synthesis was performed.

      3. Results

      3.1 Study identification and selection

      Fig. 1 shows the flow of studies through the review. The literature search identified 1495 potentially relevant citations. After the initial screen based on titles and abstracts, 107 articles were selected for full text evaluation. Following detailed assessment of the full articles, 4 were excluded because (i) was based on a study protocol (n = 1); (ii) based on selected patients (n = 1); (iii) was a duplicate study (n = 1); and (iv) was based on an online survey (n = 1). The remaining 103 articles met the inclusion criteria and were included in the review (Supplementary Appendix 5).
      Fig. 1
      Fig. 1Selection of studies included in the review.

      3.2 Study characteristics and study quality

      Table 1 summarises the key baseline characteristics of the included studies. Most studies were published in 2020, with only 8.7% in 2021. Studies were conducted across 6 continents: 56 in Europe; 25 in North America; 13 in Asia; 3 in South America and 2 each in North America and Oceania. One study was conducted in 17 countries across 4 continents and one in 4 countries across 3 continents. Most studies were retrospective cohort designs (n = 78), followed by cross-sectional designs (n = 15), prospective cohort designs (n = 9) and one ecological retrospective study. Sources of data were healthcare institutions/centres, registries and established databases. Except for one, all studies reported data for a period during the pandemic (ranging from January to October 2020) and compared this to data in the pre-pandemic period (ranging from October 2019 to March 2020) and/or a historical period (similar periods ranging from 2014 to 2019) or compared lockdown with pre-lockdown data based on date of lockdown in the particular country of the study. In the study by Metzler and colleagues [
      • Metzler B.
      • Siostrzonek P.
      • Binder R.K.
      • Bauer A.
      • Reinstadler S.J.
      Decline of acute coronary syndrome admissions in Austria since the outbreak of COVID-19: the pandemic response causes cardiac collateral damage.
      ], data was collected from 2 to 29 March 2020 and comparisons were made between the first and last week of the period surveyed. For studies that provided data on age, mean age of patients ranged from 49 to 78 years and the mean ages were similar comparing patients between the pandemic and pre-pandemic periods. The percentage of males also appeared to be similar across both periods. Among the observational cohort studies, quality score using NOS ranged from 5 to 8 and that for the cross-sectional studies ranged from 4 to 6 (Table 1).
      Table 1Baseline characteristics of included studies.
      Author, year of publicationPeriod of data collectionPandemic period/lockdownPre-pandemic period/pre-lockdownHistorical control period/pre-COVID-19Study designCountryLocationSource of dataMale %Average ageQuality score
      Araiza-Garaygordobil, 202112 Mar to 15 Apr, 20201 Dec 2019 to 11 Mar 2020Dec 2018 to April 2019Ecological retrospective study17 countriesIntercontinentalNA
      Mafham, 20201 Jan 2019 to 24 May, 2020March to May 2020Jan 2019 to Feb 2020Retrospective cohortEnglandEuropeAcute NHS hospital trusts6
      Perrin, 202013 Mar to 30 Apr 202013 Mar to 30 Apr 2019 and pre-pandemic period (7 Jan to 24 Feb 2020)Retrospective cohortSwitzerlandEuropeGeneva University HospitalsPandemic (80); Control (75)Pandemic (63.8); Control (68.0)6
      Tam, 20201 Nov 2019 to 31 Mar 2020After 25 Jan 2020Before 25 Jan 2020Cross-sectional studyHong KongAsiaAccident and Emergency DepartmentPandemic (70.3); Pre-pandemic (65.9)Pandemic (69.4); Pre-pandemic (69.0)6
      Toniolo, 2020Mar-20Mar-19Retrospective cohortItalyEuropeCardiology Division of Udine University Hospital6
      Huet, 202017−22 Mar 20202−6 Mar 2020Cross-sectional studyFranceEuropeIntensive cardiac units of 9 cardiology centres5
      Kwok, 2020bJan 2017 to April 2020After 23 March 2020Before 23 March 2020Retrospective cohortUKEuropeBritish Cardiovascular Intervention Society-National Institute of Cardiovascular Outcomes Research database7
      Boukhris, 20201 Jan to 30 April 20201 Jan to 30 April 2019Cross-sectional studyRussia, Brazil, Saudi Arabia, TunisiaIntercontinental5
      Braiteh, 2020March to April 2020March to April 2019Retrospective cohortUSANorth AmericaUpstate New York HospitalsPandemic (70.1); Control (61.9)Pandemic (65.1); Control (72.3)6
      Butt, 2020January and March 2020Mar-19Retrospective cohortQatarAsiaHamad Medical Corporation6
      De Filippo, 202020 Feb to 31 March 20201 Jan to 19 Feb 202020 Feb to 31 March 2019Retrospective cohortItalyEurope15 HospitalsPandemic (76.8)Pandemic (68)6
      De Rosa, 202012−19 March 202012−19 March 2019Cross-sectional studyItalyEuropeCardiac care unitsPandemic (68); Control (67.1)6
      Fileti, 202010 March to 10 April 202010 March to 10 April 2019Retrospective cohortItalyEurope2 Hospitals with cardiac catheterization facilitiesPandemic (65.3); Control (64.9)Pandemic (69.7); Control (70.4)6
      Folino, 202020202019Cross-sectional studyItalyEurope10 Cardiological centres in Northern Italy6
      Haddad, 2020mid-March to mid-May 2020Jan to mid-March 2020mid-March to mid-May 2019Retrospective cohortCanadaNorth AmericaHospitals in the Greater Montreal areaPandemic (44); Pre-pandemic (42); Control (42)Pandemic (60.6); Pre-pandemic (61.1); Control (69.5)6
      Hauguel-Moreau, 2020Weeks 8−7, 2018−202017 Feb to 26 April 202017 Feb to 26 April 2018; 17 Feb to 26 April 2019Retrospective cohortFranceEuropeHigh volume PCI coronary unit6
      Holy, 2020Before and after 16 March 2020 (lockdown)Before and after 16 March 2019Cross-sectional studySwitzerlandEuropeUniversity Heart Center Zurich5
      Metzler, 20202−29 March 2020Cross-sectional studyAustriaEuropePCI centres4
      Montagnon, 202123 March to 5 April 202023 March to 5 April 2019Cross-sectional studyFranceEuropeHospital Sainte AnneACS - Pandemic (71.4); Control (75)/Stroke plus TIA - Pandemic (70); Control (55.6)ACS - Pandemic (67); Control (72)/Stroke plus TIA - Pandemic (73); Control (76)6
      Showkathali, 202025 March to 31 May 202025 March to 31 May 2018; 25 March to 31 May 2019Retrospective cohortIndiaAsiaTertiary referral hospitalPandemic (59); Control (72.3)6
      Sokolski, 20201 March to 30 April 20201 March to 30 April 2019Retrospective cohort12 countriesEurope15 centres in Europe7
      Solomon, 2020Before and after 4 March 2020Before and after 4 March 2019Retrospective cohortUSANorth AmericaKaiser Permanente Northern California6
      Vacanti, 20201 Jan to 30 June 20202 Jan to 30 June 2018; 1 Jan to 30 June 2019Retrospective cohortGermanyEuropeCardiology Dept6
      Yalamanchi, 202022 March to 1 August 202022 March to 1 August 2018; 22 March to 1 August 2019Retrospective cohortIndiaAsiaCardiac intensive care unit2020 (59); 2019 (63); 2018 (62)6
      Tsioufis, 20201 Jan to 30 April 20201 Jan to 30 April 2018; 1 Jan to 30 April 2019Retrospective cohortGreeceEuropeCardiology Dept of a Tertiary General Hospital6
      Gasior, 20209 March to 16 April 20209 March to 16 April 2019Retrospective cohortPolandEuropePolish National Health Fund6
      Dreger, 2020Weeks 2−21 2020Weeks 2−21 2017 to 2019Retrospective cohortGermanyEuropeHospitals in Berlin6
      Anderson, 202011 March to 28 April 202011 March to 28 April 2019Retrospective cohortUSANorth AmericaHospital in Boston6
      Gluckman, 202030 Dec 2018 to 16 May 202029 March 2020 to 16 May 202023 Feb 2020 to 28 March 202030 Dec 2018 to 22 Feb 2020Cross-sectional studyUSANorth America49 hospitals in the Providence St Joseph Health systemLater COVID-19 period (66); Early COVID-19 period (68); Historical control (66)Later COVID-19 period (67); Early COVID-19 period (67); Historical control (68)6
      Mohammad, 20201 March to 7 May 20201 March to 7 May 2015−2019Retrospective cohortSwedenEuropeSwedish Coronary Angiography and Angioplasty RegistryPandemic (67.4); Control (67.4)Pandemic (70); Control (70)6
      Piccolo, 202030 Jan to 26 March 20204 weeks after 27 Feb 20204 weeks before 27 Feb 2020Retrospective cohortItalyEuropePCI centresPandemic (75%); Pre-pandemic (72%)Pandemic (65.6); Pre-pandemic (65.8)6
      Secco, 2020Mar-20Mar-19Retrospective cohortItalyEurope3 High volume hospitalsPandemic (67.4); Control (67.4)Pandemic (67.4); Control (67.4)6
      Ayad, 20211 Feb to October 20201 Feb to October 2019Retrospective cohortEgyptAfricaInternational Cardiac Center hospitalPandemic (81.5); Control (85.7)Pandemic (57.1); Control (58.9)6
      Bhatt, 20201 Jan 2019 to 31 March 2020Mar-20Mar-19Retrospective cohortUSANorth AmericaMass General Brigham health systemPandemic (55.4); Control (57.8)Pandemic (70.3); Control (71.1)6
      Daoulah, 20211 January to 30 April 20201 January to 30 April 2018−2019Retrospective cohortSaudi ArabiaAsia16 centres2018 (89.8); 2019 (84.9); 2020 (90.8)2018 (56.7); 2019 (56.5); 2020 (55.4)6
      Desai, 2020Mar-20March 2017−2019Retrospective cohortUSANorth AmericaStroke center6
      Diegoli, 2020After 17 March 20202019Retrospective cohortBrazilSouth AmericaJoinville Stroke Registry6
      Gitt, 20201 March to 21 April 20201 March to 21 April 2017−2019Retrospective cohortGermanyEuropeHeart Center Ludwigshafen6
      Hammad, 20201 Jan to 15 April 2020After 23 March 2020Before 23 March 2020Retrospective cohortUSANorth AmericaIntegrated 18-hospital systemPandemic (49); Pre-pandemic (67)Pandemic (66); Pre-pandemic (61.8)6
      Kerleroux, 202015 Feb to 30 March 202015 Feb to 30 March 2019Prospective cohortFranceEurope32 stroke centresPandemic (51.2); Control (58.4)Pandemic (70.6); Control (71.8)7
      Montaner, 2020Before and after 31 March 2020Before and after 31 March 2019Prospective cohortSpainEuropeStroke units7
      Neves Briard, 202030 March to 31 May 202030 March to 31 May 2019Prospective cohortCanadaNorth AmericaStroke centerPandemic (48); Control (51)Pandemic (69.4); Control (72.1)8
      Pop, 20201−31 March 20201−31 March 2019Retrospective cohortFranceEurope3 Stroke unitsPandemic (65.5); Control (64)6
      Popovic, 202026 Feb to 10 May 20202008−2017Prospective cohortFranceEuropeUniversity Hospital of NancyPandemic (56.3); Control (76.1)Pandemic (62.6); Control (59.6)7
      Range, 202015 Jan 2019 to 14 April 202015 March to 14 April 2020Before 15 March 2020Prospective cohortFranceEuropeFrance PCI registryPandemic (70.5); Control (76.1)Pandemic (62.9); Control (63.6)7
      Reinstadler, 202024 Feb (week 9) to 5 April 2020 (week 14)Retrospective cohortAustriaEurope7 tertiary care hospitals73615
      Sarfo, 2020January to June 2020January to June 2019Retrospective cohortGhanaAfricaKomfo Anokye HospitalPandemic (57.1); Control (53.4)Pandemic (60.6); Control (59.7)7
      Teo, 202023 Jan to 24 March 202023 Jan to 24 March 2019Retrospective cohortHong KongAsiaQueen Mary HospitalPandemic (43.8); Control (50.6)Pandemic (70.1); Control (73.6)6
      Toner, 202016 March to 15 April 202016 March to 15 April 2014−2019Prospective cohortAustraliaOceaniaTertiary hospitalPandemic (65.0); Control (71.6)Pandemic (68.1); Control (65.0)7
      Abdelaziz, 20201−31 March 20201−31 March 2019Retrospective cohortUKEuropeTertiary cardiac centerPandemic (69.6); Control (76.8)Pandemic (63.2); Control (66.6)6
      Agarwal, 202001 June 2019 to 15 May 20201 March 2020 to 15 May 20201 June 2019 to 29 Feb 2020Retrospective cohortUSANorth AmericaLangone Health Stroke CenterPandemic (49.2); Pre-pandemic (54.7)Pandemic (68); Pre-pandemic (72)6
      Burgos, 2020Feb to March 2020Feb to March 2019Retrospective cohortArgentinaSouth AmericaCardiology center6
      Aldujeli, 202011 March to 20 April 202011 March to 20 April 2019Retrospective cohortLithuaniaEuropeLithuanian University of Health Sciences Kaunas ClinicsNSTEMI: Pandemic (73); Control (60)/STEMI: Pandemic (72); Control (65)NSTEMI: Pandemic (70); Control (69.5)/STEMI: Pandemic (67); Control (68.5)6
      Andersson, 20201 Jan to 11 March 2020/12–31 Mar 20201 Jan to 11 March 2019/12–31 Mar 2019Retrospective cohortDenmarkEuropeDanish Nationwide Patient RegistryPandemic: New-onset HF (61−62); Worsening HF (69−72)/Control: New-onset HF (62); Worsening HF (66−67)Pandemic: New-onset HF (73.3−74.8); Worsening HF (74.0−75.2)/Control: New-onset HF (73.4−74.3); Worsening HF (75.2−75.3)7
      Ball, 202028 Oct 2019 to 10 May 202028 Oct 2019 to 10 May 2018−2019Cross-sectional studyUKEurope9 Hospitals6
      Boeddinghaus, 2020March to April 2020Jan to Feb 2020March to April 2019Retrospective cohortSwitzerlandEuropeTertiary University HospitalPandemic (77.5); Pre-pandemic (76.8)Pandemic (66); Pre-pandemic (68)6
      Bromage, 20202 March to 19 April 20202 March to 19 April 2017−2019Retrospective cohortUKEuropeKing’s College HospitalPandemic (54); Control (58)Pandemic (73); Control (71)6
      Bryndza, 2021March to April 2020March to April 2020Retrospective cohortPolandEuropeCardiology center6
      Cammalleri, 20201−31 March 2020Mar-19Retrospective cohortItalyEuropeCardiology DepartmentPandemic (85); Control (87)Pandemic (65); Control (62)6
      Candelaresi, 20219 March to 12 April 20202 Feb to 8 March 2020Same period in 2019Retrospective cohortItalyEurope5 Campania stroke hubs6
      Chew, 20217 Feb to 31 March 20201 October 2019 to 6 Feb 2020Retrospective cohortSingaporeAsiaNational University Hospital SingaporePandemic (56.8); Pre-pandemic (64.4)Pandemic (59); Pre-pandemic (57)7
      Choudhary, 202025 March to 24 April 202025 Feb to 24 March 202025 Jan to 24 Feb 2020Retrospective cohortIndiaAsia4 Tertiary regional Eds6
      Çinier, 20205 March to 6 April 20205 March to 6 April 2020Retrospective cohortTurkeyEuropeDr. Siyami Ersek Thoracic and Cardiovascular Surgery Training and Research HospitalPandemic (81.1); Control (85.6)Pandemic (59.3); Control (63.7)7
      Colivicchi, 202020 Feb to 20 April 202020 Feb to 20 April 2019Retrospective cohortItalyEuropeSan Filippo Neri HospitalPandemic (79); Control (57)Pandemic (78); Control (73)7
      Cummings, 2020March to April 2020March 2019 to Feb 2020Retrospective cohortUSANorth AmericaTelestroke registry at Medical University of South CarolinaPandemic (44); Control (46.9)Pandemic (69); Control (67)6
      Del Pinto, 20201 January to 31 March 20201 January to 31 March 2019Retrospective cohortItalyEurope5 Hospitals in L'Aquila6
      Enache, 2020First 3 months of 2020First 3 months of 2019Retrospective cohortMonacoEuropeCardiology Departments6
      Erol, 202017 April to 2 May 20201−15 November 2018Prospective cohortTurkeyEuropeRegistriesPandemic (76.2); Control (73.7)Pandemic (60); Control (62)8
      Frisullo, 202011 March to 11 April 202011 March to 11 April 2019Retrospective cohortItalyEuropeED of Policlinico A. Gemelli HospitalPandemic (59.6); Control (46.3)Pandemic (71.6); Control (73.7)6
      Giannouchos, 20211 Jan to 31 Aug 20201 Jan to 31 Aug 2019Cross-sectional studyUSANorth AmericaUniversity of Utah Healthcare Systems6
      Hoyer, 2020Weeks 1−15 2020Weeks 1−15 2019Retrospective cohortGermanyEurope4 stroke centers6
      Hsiao, 2020Weeks 11−15 2020Weeks 1−10 2020mid-March to mid-April 2019Retrospective cohortUSANorth America30 Healthcare facilities6
      JF Huang, 202011 March to 9 April 202010 Feb to 10 March 2020Cross-sectional studyUSANorth AmericaMayo Clinic telestroke network6
      Ikenberg, 20201 Jan to 19 April 202021 March to 19 April 20201 Jan to 20 March 2020Retrospective cohortGermanyEuropeBavarian Comprehensive Stroke Center6
      Jasne, 20201 Jan to 28 April 20201 Jan to 28 April 2019Cross-sectional studyUSANorth America3 Connecticut hospitals49.7706
      John, 20201 March to 10 May 20201 March to 10 May 2019Retrospective cohortUAEAsiaCleveland Clinic Abu DhabiPandemic - Ischemic stroke (72.3); hemorrhagic stroke (66.7); Control - Ischemic stroke (67.9); hemorrhagic stroke (80.8)Pandemic - Ischemic stroke (57.5); hemorrhagic stroke (48.9); Control - Ischemic stroke (58.4); hemorrhagic stroke (49.3)6
      Kobo, 202020 March to 30 April 202020 March to 30 April 2019Prospective cohortIsraelAsia4 Cardiac centersPandemic (84.1); Control (81.5)Pandemic (63); Control (61)8
      Kuitunen, 20201 February to 30 April 20206 weeks after 16 March 20206 weeks before 16 March 2020Corresponding period in 2019Retrospective cohortFinlandEurope3 Emergency Departments6
      Lauridsen, 202012 March to 13 May 202012 March to 13 May 2015−2019Retrospective cohortDenmarkEuropeDanish Civil Population RegistryPandemic (71); Control (75)Pandemic (69); Control (70)7
      Little, 20201 March to 30 April 20201 March to 30 April 2019Retrospective cohortUKEurope7 Heart Attack CentresPandemic (80); Control (78)Pandemic (63); Control (63)6
      Nagamine, 2020March to April 2020March to April 2019Retrospective cohortUSANorth AmericaStroke centerPandemic (75); Control (61)Pandemic (65.3); Control (69)6
      Mitra, 202026 March to 23 April 202026 March to 23 April 2019Cross-sectional studyAustraliaOceaniaTertiary cardiology and neurosciences centrePandemic (67.3); Control (84.2)Pandemic (71.1); Control (74.7)6
      Nguyen-Huynh, 202015 March to 9 May 20201 Jan 2019 to 14 March 2020Retrospective cohortUSANorth AmericaKaiser Permanente Northern CaliforniaPandemic (47.9); Pre-pandemic (47.1)Pandemic (69); Pre-pandemic (68.8)7
      Oseran, 20201 March to 30 April 20201 Jan to 29 Feb 20201 March to 30 April 2019/1 Jan to 28 Feb 2019Cross-sectional studyUSANorth America8 Acute care hospitals6
      Paliwal, 2020November 2019 to April 20207 Feb to 30 April 20201 Nov 2019 to 7 Feb 2020Retrospective cohortSingaporeAsiaStroke centerPandemic (57); Pre-pandemic (20)Pandemic (64.6); Pre-pandemic (65.6)6
      Papafaklis, 20202 March to 12 April 20202 March to 12 April 2019Retrospective cohortGreeceEuropePublic hospitalsPandemic (79.1); Control (76.2)Pandemic (64.3); Control (64)6
      Piuhola, 2020Mar-20Jan to Feb 2020January to Feb 2017−2019Retrospective cohortFinlandEurope5 Tertiary centers6
      Rashid Hons, 20201 Feb to 14 May 20201 Feb to 14 May 2019Retrospective cohortUKEuropeMyocardial Ischaemia National Audit Project/British Cardiovascular Intervention SocietyPandemic (71.2); Control (79.5)Pandemic (67.1); Control (63.1)7
      Richter, 202116 March to 15 May 202016 Jan to 15 March 202016 March to 15 May 2019Retrospective cohortGermanyEurope1463 Hospitals6
      Rodríguez-Leor, 202016 March to 14 April 20201−30 April 2019Retrospective cohortSpainEurope75 STEMI care centersPandemic (78.4); Control (78.4)Pandemic (63.1); Control (63.7)7
      Ruparelia, 2020After 20 March 2020Jan to Feb 2020Jan to March 2019Retrospective cohortUKEurope2 Large HospitalsPandemic (65.3); Control (68.9)Pandemic (75.4); Control (73.2)6
      Schirmer, 2020Feb to March 2020Feb to March 2019Retrospective cohortUSANorth America12 Stroke centersPandemic (67); Control (70)6
      Seiffert, 20201 Jan 2019 to 31 May 2020Jan to May 2020Jan to May 2019Retrospective cohortGermanyEuropeInsurance Claims Data6
      Sharma, 202030 Dec 2019 to 19 April 202031 Dec 2018 to 21 April 2019Retrospective cohortUSANorth America5 Tertiary stroke centers6
      Siegler, 20201 March 2020 to 15 April 20201 October 2019 to 29 Feb 2020Retrospective cohortUSANorth AmericaStroke centerPandemic (57); Control (59)Pandemic (68); Control (68)7
      Tejada Meza, 202030 Dec 2019 to 3 May 2020After 14 March 2020Before 14 March 2020Retrospective cohortSpainEuropeTertiary hospitals of the NORDICTUS network6
      Uchino, 20209 March to 2 April 20201 Jan to 8 March 2020Retrospective cohortUSANorth America19 Emergency departments6
      Vensentini, 2020March to April 2020March to April 2010−2019Prospective cohortArgentinaSouth America6 Cardiovascular Intensive Care Units7
      Wadhera, 202118 March to June 20201 Jan to 17 March 2020Jan to June 2019Retrospective cohortUSANorth AmericaNational Center for Health Statistics6
      J Wang, 202012 March to 30 June 20201 Dec 2019 to 11 Mar 2020Retrospective cohortUSANorth AmericaInova Fairfax Medical CampusPandemic (53.3); Pre-pandemic (51.9)Pandemic (73); Pre-pandemic (70)6
      Yang, 202023 Jan to 7 March 20201 December 2019 to 14 Jan 2020Retrospective cohortChinaAsiaStroke centerPandemic (71.4); Pre-pandemic (64.7)Pandemic (62.3); Pre-pandemic (65.2)6
      Zhao, 2020Feb-20Feb-19Retrospective cohortChinaAsiaBig Data Observatory Platform for Stroke of China & 280 stroke centers6
      Cox, 202022 March to 20 April 202022 March to 20 April 2019Retrospective cohortUSANorth AmericaVanderbilt University Medical Center6

      3.3 Cardiovascular diseases

      Table 2 provides details of various cardiovascular diseases that were assessed by eligible studies and specific outcomes reported. The majority of studies (n = 65) assessed hospitalisations for ACS (STEMI, NSTEMI or both) only, ACS patients undergoing percutaneous coronary intervention (PCI) or a combination of ACS and other cardiovascular conditions such as HF, strokes. Other outcomes assessed were stroke hospitalisations (n = 30); acute HF (n = 5); cardiometabolic conditions such as hypertension, diabetes, VTE and arrhythmias (n = 2) and CVD deaths (n = 1).
      Table 2Trends in hospitalisations of cardiometabolic conditions and severity at presentation.
      Author, year of publicationCardiometabolic conditionHistorical control/pre-COVID-19 hospitalisationsPre-pandemic/pre-lockdown hospitalisationsPandemic/lockdown hospitalisationsTrends in hospitalisations for cardiometabolic outcomesSeverity of presentation
      Araiza-Garaygordobil, 2021ACS admissions875059231444Compared to the pre-pandemic period, a significant overall trend for reduction of 20.2% in the weekly number of ACS hospitalizations was observed during the pandemic period. There were also reductions when compared to the historical period.
      Mafham, 2020ACS admissionsMonthly average for 2019 (13,075); Jan 2020 (13,645); Feb 2020 (12,443)Mar 2020 (10,118); Apr 2020 (8739); May 2020 (9756)From mid-February 2020, hospital admissions fell from a 2019 baseline rate of 3017 admissions per week to 1813 per week by the end of March, 2020 (reduction of 40%). This decline was partly reversed during April and May, 2020, such that by the last week of May, 2020, there were 2522 admissions, representing a 16% reduction from baseline.
      Perrin, 2020Undergoing PCI for ACS14045The incidence rate of ACS was lower during the COVID-19 period than the control period (0.7 vs 1.1 per 1000 person-years, p < 0.01). There were significantly more patients presenting with out-of-hospital cardiac arrest during the COVID-19 period compared with the control period (22.2% vs 7.1%, p < 0.01).ACS patients presented higher cardiac enzymes during the COVID-19 period compared with the control period.
      Tam, 2020MI admissions8564There was a reduction in daily emergency room attendance since January 25, 2020 (231 per day compared to 327 per day before the pandemic)
      Toniolo, 2020Severe emergent CVD admissions7134A decrease was observed in all SECDs hospital admissions comparing the pandemic to the control period: 27 versus 19 for STE-ACS (−30%); 44 versus 15 for non-STE-ACS (−66%) and 46 versus 23 for atrioventricular-block/acute sinus node dysfunction (−50%).
      Huet, 2020Acute myocardial infarction or acute heart failure admissionsBefore containment, the nine participating intensive cardiac care units admitted 4.8 ± 1.6 patients per day, versus 2.6 ± 1.5 after containment.
      Kwok, 2020bPCI procedures for STEMI33,255683A 43% decline in monthly average procedures was recorded between 2017 and 2019 (865) to 497 in April 2020
      Boukhris, 2020Volume of ACS and ischemic strokesACS (2398); ischemic stroke (4027)ACS (2215); ischemic stroke (3905)ACS volume tended to increase in January and February 2020 in comparison to the same period in 2019. In March and April 2020, STEMI and NSTEMI decreased in comparison with March and April 2019. There was a gradual decrease in stroke cases from January to March 2020 compared to 2019, followed by an increase in April 2020.
      Braiteh, 2020ACS admissions11367Drop by 40.7% in total ACS cases during the pandemic in comparison to 2019
      Butt, 2020ACS, other CVDs, strokeACS (171); other CVDs (116); stroke (109)March 2020 - ACS (114); other CVDs (64); stroke (83)Compared to March 2019, there was a decrease in ACS, other CVDs, and stroke by 50%, 81.3% and 31.3% respectively, in March 2020
      De Filippo, 2020ACS admissionsACS (756)ACS (899)ACS (547)13.3 ACS admissions/day during the pandemic period compared to 18.0 for the pre-pandemic period and 18.9 for the historical period. The corresponding values for STEMI were 6.1, 7.8 and 8.0. That for NSTEMI were 4.2, 7.1 and 7.5. Unstable angina was 3.1, 3.1 and 3.4.
      De Rosa, 2020AMI admissionsAMI (618); STEMI (268); NSTEMI (350)AMI (319); STEMI (197); NSTEMI (122)48.4% reduction in AMI admissions during the pandemic period compared to 2019. Reductions were significant for both STEMI and NSTEMI. The reductions for STEMIs were higher for women compared to men. Reductions in admissions for HF, AF and PE during the pandemic compared to 2019.
      Fileti, 2020ACS admissionsACS (94); STEMI (36); NSTEMI (58)ACS (72); STEMI (34); NSTEMI (38)23.4% reduction in ACS admissions during 2020 compared to 2019, with a decrease for both STEMI and NSTEMI
      Folino, 2020Access to coronary care unit for ACSNSTEMI in first 8 weeks of 2019 (260) and 221 in the following 5 weeks. Corresponding values for STEMI were 22 and 21After the eighth week of 2020, there was a significant reduction in access to CCU for NSTEMI compared to the same period of the previous year, but not for STEMI.
      Haddad, 2020STEMI admissions605453Number of STEMI admissions were unaffected during the pandemic period
      Hauguel-Moreau, 2020ACS admissionsIn 2020, there were two distinct phases in ACS admissions - a first significant fall, with a relative reduction of 73%, from the week of lockdown (week 12) to 3 weeks later followed by an increase
      Holy, 2020ACS and OHCA referralsFour weeks after March 16th 2020 ACS referrals decreased by 42% (NSTEMI: –49%, STEMI: –56%, unstable angina: +37%) while OHCA referrals declined by 57%
      Metzler, 2020ACS admissionsComparing the first and last calendar week of the period surveyed, there was a relative reduction of 39.4% in admissions for ACS. STEMI admissions reduced from 94 to 70 and NSTEMI from 132 to 67
      Montagnon, 2021Admissions for ACS and strokesACS (12); Stroke or TIA (27)ACS (7); Stroke or TIA (30)There were five fewer cases of ACS in 2020, a reduction of 41.7% compared with 2019. In 2020, an increase was observed in the number of strokes and TIAs, with 27 cases in 2019 as opposed to 30 in 2020.
      Showkathali, 2020ACS admissions183104During the study period in 2020, 104 patients were admitted with ACS, which is a 43% decline in admissions compared to the same time period in the previous 2 years (183). The decline in STEMI, NSTEMI and unstable angina admissions were 47%, 33%, and 54% respectively
      Sokolski, 2020Cardiovascular admissions44523007In 2020, there were fewer admissions for ACS, acute HF, arrhythmia, and others. There was a relatively higher percentage of pulmonary embolism admissions in 2020
      Solomon, 2020AMI admissionsThe weekly rates of hospitalization for AMI decreased by up to 48% during the Covid-19 period
      Vacanti, 2020ACS admissions2018 (326); 2019 (353)270Decline in ACS admissions in 2020 compared to 2019 and 2018, representing a decline of 24% and 19%, respectively.
      Yalamanchi, 2020ACS admissions2018 (307); 2019 (322)216Decline in ACS admissions in 2020 compared to 2019 and 2018, representing a decline of 33% and 30%, respectively.There was a decline in admissions for acute decompensated heart failure, arrhythmia, and other diagnoses in 2020, which were 38%, 62%, and 59%, respectively; while there was a 50% increase in acute pulmonary embolism admission compared to the mean admission in 2018 and 2019
      Tsioufis, 2020AMI admissionsThe number of AMI cases in March 2020 was the lowest compared to the entire three year period. Similar significant findings were observed for STEMI and NSTEMI. Cases of HF and CAD were also lower in 2020 compared to the preceeding periods
      Gasior, 2020AMI admissionsThe number of admissions for AMI dropped on average by 43.6%
      Dreger, 2020AMI admissions2017 (255); 2018 (250); 2019 (257)207There was a reduction in AMI admissions in 2020 compared with the same time period in the three previous years.
      Anderson, 2020Admissions for cardiometabolic conditionsOverall decrease in cardiometabolic conditions (CVD, strokes, VTE, HF and diabetes)
      Gluckman, 2020AMI admissions13,329Early COVID-19 period (860)Later COVID-19 period (1055)Beginning February 23, 2020, AMI-associated hospitalizations decreased for 5 weeks (early COVID-19 period). Thereafter, AMI-associated hospitalizations increased during the later COVID-19 period
      Mohammad, 2020MI cases referred for coronary angiography15,2132443The incidence of MI referred for invasive treatment was reduced during the COVID-19 pandemic
      Piccolo, 2020PCI procedures for ACS178 cases/100,000 residents per year120/100,000 residents per yearDuring the 8 week period, there was a decline by 32% in the number of PCIs for ACS. In the last 2 weeks of the observational period, PCIs for ACS were reduced by 50%. The reduuction was similar for STEMI and NSTEMI
      Secco, 2020ACS admissions16284Hospitalization for ACS decreased from 162 patients in 2019 to 84 patients in 2020
      Ayad, 2021STEMI patients requiring PCI364270During the COVID-19 period, the number of PCI procedures was reduced by 25.7% compared with previous year
      Bhatt, 2020Acute cardiovascular conditions404231There were 43.4% fewer estimated daily hospitalizations in March 2020 compared with March 2019
      Daoulah, 2021STEMI admissions2018 (650); 2019 (635)500STEMI volumes were reduced by 28% during the pandemic period
      Desai, 2020Stroke and TIA admissionsStrokes - 2017 (163); 2018 (161); 2019 (159)/TIA – 2017 (11); 2018 (18); 2019 (16)Stroke (96); TIA (6)Number of acute ischemic strokes and TIAs decreased by 40% and 60% respectively, from March 2017−2019 to March 2020
      Diegoli, 2020Stroke admissions12.9 cases/100,0008.3 cases/100,000When compared with the same period in 2019, there was a 36.4% reduction in stroke admissions in 2020No differences in admissions for stroke severity
      Gitt, 2020ACS admissionsSTEMI (49); NSTEMI (95); UA (94)STEMI (46); NSTEMI (50); UA (48)During the pandemic, there was a 50% reduction in both unstable angina and NSTEMI
      Hammad, 2020STEMI admissions10835Lower STEMI admissions during the pandemic period.Post-COVID-19 presentation was severe compared to pre-COVID-19
      Kerleroux, 2020Stroke patients receiving mechanical thrombectomy844668There was a 21% significant decrease in MT case volumes during the pandemic period
      Montaner, 2020Stroke admissions25% reduction in stroke admissions during the pandemic period. 40% reductions in TIAs attending the emergency department
      Neves Briard, 2020Stroke admissions138156The first two months of the COVID-19 pandemic were not associated with a decrease in acute stroke evaluations
      Pop, 2020Stroke admissions167122Compared to the same period in 2019, there were 39.6% fewer stroke alerts in 2020
      Popovic, 2020STEMI patients undergoing PCI155283
      Range, 2020STEMI patients undergoing PCI1942122There was a significant drop (12%) in mean number of STEMI/month in the lockdown group compared with prelockdown (139 vs 122, p < 0.04).
      Reinstadler, 2020STEMI patients referred for PCI163Rates of STEMI admissions decreased (calendar week 9/10 (n = 69, 42%); calendar week 11/12 (n = 51, 31%); calendar week 13/14 (n = 43, 26%)
      Sarfo, 2020Stroke admissions401431Stroke admissions were higher during the pandemic period (increase of 7.5%). Recurrent stroke admissions were also higher during the pandemic period
      Teo, 2020Stroke admissions8973Fewer stroke admissions in pandemic periodNo differences in stroke severity
      Toner, 2020ACS undergoing PCI10220The case volume for the number of ACS patients undergoing PCI was not significantly different in the COVID and non-COVID eras
      Abdelaziz, 2020STEMI patients undergoing PCI6946Fewer STEMI admissions in the pandemic periodHigher cardiac troponin-I levels on admission in STEMI patients during pandemic than pre-COVID era
      Agarwal, 2020Acute ischemic stroke care634120Fewer admissions during pandemic compared to pre-pandemicPandemic patients presented with a higher median admission NIHSS scores.
      Burgos, 2020HF admissions493626.5% decrease in number of HF admissions during the pandemic period
      Aldujeli, 2020AMI admissionsNSTEMI (62); STEMI (60)NSTEMI (30); STEMI (47)Fewer admissions during pandemic compared to pre-pandemic
      Andersson, 2020New-onset and worsening HF admissionsNew-onset HF (2819); Worsening HF (1419)New-onset HF (2595); Worsening HF (1364)In the lockdown period, rates of new-onset HF diagnoses and of hospitalizations for worsening HF were significantly lower in 2020 versus 2019
      Ball, 2020CVDs admissionsActivity for cardiac, cerebrovascular and other vascular conditions started to decline 1–2 weeks before lockdown and fell by 31%–88% after lockdown, with the greatest reductions observed for coronary artery bypass grafts, carotid endarterectomy, aortic aneurysm repair and peripheral arterial disease procedures, compared with the previous year.
      Boeddinghaus, 2020ACS admissions220178Compared to January/February 2020, there was a dramatic reduction of ED presentations after the COVID-19 outbreak on March 1st (31% relative reduction). Comparing March/April 2020 to that of 2019, there was a 38.7% reduction in ED presentations
      Bromage, 2020HF admissions7826Significantly lower admission rate for HF was observed during the study covid-19 pandemic compared to all other included time periods.Patients admitted during the COVID-19 pandemic had higher rates of NYHA III or IV symptoms and severe peripheral oedema
      Bryndza, 2021AMI admissions1055827In comparison to the control period, there was a 21.6% decrease in the total number of AMI cases (a 18.6% decrease in the number of patients with STEMI and a 23.9% decrease in the number of patients with NSTEMI).
      Cammalleri, 2020STEMI patients undergoing PCI3513During March 2020, there was a 63% reduction of patients with STEMI admitted for PCI, when compared with the same period of 2019Patients in 2020 had higher levels of cardiac biomarkers and a worse left ventricular ejection fraction at baseline
      Candelaresi, 2021Stroke admissionsThe global number of patients presenting with acute stroke did not significantly differ between the periodsBaseline NIHSS score was significantly more severe during the lockdown compared to the same period of 2019 and tended to be more severe compared to the immediate prelockdown phase
      Chew, 2021STEMI patients undergoing PCI20895Fewer admissions during pandemic compared to pre-pandemic
      Choudhary, 2020Cardiovascular emergencies (ACS, acute decompensated HF and high degree AV block)1488830289Fewer emergency cardiovascular admissions during the lockdown period than the pre-lockdown and pre-COVID periods.Risk factors associated with poorer prognosis in ACS were higher in patients during the lockdown and pre-lockdown period compared to pre-COVID period.
      Çinier, 2020STEMI patients undergoing PCI17490Significant reduction in STEMI cases during COVID-19 pandemic compared to previous year
      Colivicchi, 2020Acute HF admissions60602711The number of patients with acute HF decreased by 49% during the pandemic periodRisk factors associated with poorer prognosis were higher in patients during the pandemic compared to the pre-COVID period
      Cummings, 2020Tele stroke consulations5239613Fewer stroke patients were seen during the pandemic. The median number of weekly consults dropped from 112 to 77 during the pandemic. Black patients were less likely to present with strokes during the pandemic
      Del Pinto, 2020CVDs admissionsLess cardiovascular hospitalizations occurred in 2020 than in 2019
      Enache, 2020CVDs admissions419346Compared to March 2019, the total cardiovascular admissions were lower by 17%. Similarly, compared to March 2019, cardiovascular emergency admissions were down by 21%.
      Erol, 2020AMI admissions1872991There was a 47.1% decrease in acute MI admissions during the pandemic. This reduction in admission was more prominent in patients with NSTEMI compared with STEMI
      Frisullo, 2020Ischemic stroke admissions4152No significant difference observed between 2019 and 2020 in number of admissions
      Giannouchos, 2021ED visits for medical conditions (included hypertension and diabetes)Hypertension (461); diabetes (300)Hypertension (251); diabetes (209)Decrease in ED visits for both hypertension and diabetes
      Hoyer, 2020Ischemic stroke admissionsA significant decrease in the number of admissions for transient ischemic attack was observed in 3 of 4 centers during the pandemic
      Hsiao, 2020Stroke consultationsCompared with the 10 weeks prior, stroke consultations declined by 39% in the 5 weeks after announcement of COVID-19 mitigation measures. Results compared with the prior year and time trend analyses were consistent
      JF Huang, 2020Tele stroke activations14271There was a 50% reduction in stroke volume activations during the post-pandemic declaration period
      Ikenberg, 2020Stroke referrals17170The absolute daily number of Code Stroke referrals and the portion of patients with stroke mimics remained stable. The portion of female stroke patients decreased (55% to 33%; p = 0.03) during the lockdown.Stroke severity as measured by the NIHSS increased during the lockdown.
      Jasne, 2020Stroke code activations786756There was a significant decline in weekly stroke code volumes at the 3 hospitals from January to April, 2020. 30% decrease in total stroke codes during the pandemic weeks in 2020 versus 2019There was no difference in stroke severity
      John, 2020Stroke admissions148210There was a 41.9% increase in stroke admissions in 2020. The difference in 2020 was driven by significant increases in ischemic stroke, intracerebral hemorrhage and stroke mimics.Ischemic stroke: Severity of stroke presentation was higher in 2020 as recorded by the NIHSS.
      Kobo, 2020STEMI patients undergoing PCI136107There was a 22% decrease in STEMI admissionsPatients admitted in 2020 had higher admission and peak troponin levels
      Kuitunen, 2020ED visits and inpatient admissions for medical conditions (included AMI, strokes and other heart disease)Stroke (553); AMI (650); other heart disease (1837)Stroke (558); AMI (645); other heart disease (1513)The visit rate and inpatient admissions due to AMI and strokes remained stable throughout the study period.
      Lauridsen, 2020AMI admissionsAMI (11,769); AMI-CS (342)AMI (2132); AMI-CS (60)The total number of MI patients decreased by 15% during lockdown comparing the average number of MI admissions in 2015–2019 with the number of MIs in 2020The incidence proportions of AMI-related cardiogenic shock were similar during lockdown comparing 2015–2019 and 2020
      Little, 2020STEMI admissions440348There was a 21% reduction in STEMI admissions in 2020 vs in 2019
      Nagamine, 2020Ischemic stroke admissions6848There was reduction in stroke admissions in 2020 compared to 2019
      Mitra, 2020Acute stroke and AMI admissions5752There was a 9.6% reduction in stroke and AMI admissions in 2020 compared to 2020
      Nguyen-Huynh, 2020Acute stroke presentations8337783Stroke volumes decreased significantly post lockdown compared with pre-lockdownPost-lockdown patients had higher NIHSS scores, lower comorbidity score, and arrived more often by ambulance. Post-lockdown patients also had large vessel occlusions.
      Oseran, 2020Cardiovascular admissionsDuring the pandemic period, there was a decrease in admission rates for all conditions including cardiovascular conditions
      Paliwal, 2020Stroke admissions206144Decline in stroke activationsIn terms of stroke severity, the median NIHSS on arrival was similar
      Papafaklis, 2020ACS admissions1077771ACS admissions in the COVID-19 period were reduced by 28.4% compared to 2019During the COVID-19 period, patients admitted with ACS presented more frequently with left ventricular systolic impairment
      Piuhola, 2020STEMI admissionsDuring 2017–2019, there were no marked differences in STEMI incidence between January, February and March. During 2020, there was an average drop of 32% in STEMI incidence in March.
      Rashid Hons, 2020AMI admissions with OHCA731524AMI hospitalizations during COVID-19 period were reduced by >50%
      Richter, 2021Stroke admissionsDecline in hospitalizations during the pandemic compared to the pre-pandemic period
      Rodríguez-Leor, 2020STEMI admissions13051009Suspected STEMI patients treated in STEMI networks decreased by 27.6% with a reduction in confirmed STEMI cases by 22.7% during the pandemic
      Ruparelia, 2020ACS admissions376280There was a significant reduction in the entire spectrum of ACSs following the beginning of the COVID-19 pandemic
      Schirmer, 2020Stroke admissions320163In the COVID period in 2020, there was a drop in the absolute number of cases per calendar weekThere was no difference in the severity of the presentation between groups
      Seiffert, 2020Admissions for AMI, acute limb ischemia, aortic rupture, stroke or TIA78.6/100,00070.6/100,000Monthly admission rates declined from pre-COVID to COVID periods. The lowest admission rate was observed in April 2020
      Sharma, 2020Stroke and TIA admissionsThere was a decline in stroke/TIA admissions and ED stroke alerts during 30 December 2019 to 19 April 2020. The greatest decline in hospital admissions was observed between 23 March and 19 April 2020Baseline NIHSS score was higher in the pandemic period
      Siegler, 2020Stroke admissions27553There was a mean fall of 38% in new stroke diagnosesNo difference with respect to severity of stroke
      Tejada Meza, 2020Stroke admissions173/week124/weekThere was a decrease in the weekly mean admitted patients during the pandemic
      Uchino, 2020Stroke presentations10 alerts/day8 alerts/dayThere was a significant decrease in acute stroke presentations by 30% across emergency departments during the COVID-19 periodStroke severity measured by NIHSS was unchanged.
      Vensentini, 2020CVDs admissionsAverage (595)Average (348)The average number of CVD admissions decreased by 46.8% during the COVID-19 period. Reductions in cardiovascular surgery 72.3%, electrophysiological interventions 67.8%, NSTEMI 52.6%, angioplasties 47.6%, arrhythmias 48.7%, heart failure 46%, atrial fibrillation 35.7%, STEMI 34.7%, non cardiac chest pain 31.8% and others 51.6% during the COVID-19 period. Hypertensive crisis increased by 89%
      Wadhera, 2021CVD deaths199,311197,731Deaths caused by ischemic heart disease and hypertensive disease increased nationally after the onset of the pandemic in 2020, compared with changes over the same period in 2019, but not for heart failure, cerebrovascular disease, or other diseases of the circulatory system.
      J Wang, 2020Acute ischemic stroke admissions320255There was a 22.1% and 39.5% decline in admission for acute ischemic stroke in April and May 2020, respectively.Stroke severity at presentation measured by NIHSS was unchanged.
      Yang, 2020Acute stroke patients undergoing endovascular thrombectomy3421Decline in acute stroke patients undergoing endovascular thrombectomy during the pandemic eraStroke severity at presentation measured by NIHSS was unchanged.
      Zhao, 2020Stroke careHospital admissions related to stroke dropped by 40%
      Cox, 2020Acute HF admissions62% decrease in HF admissions during the pandemic period relative to last yearSeverity at admission was unchanged

      3.4 Trends in hospitalisations for cardiovascular diseases

      Trends in hospitalisations for cardiovascular diseases are reported in Table 2. Except for 12 studies, all others reported a decline in the outcomes assessed during the pandemic period compared to the pre-pandemic period. The declines ranged from 20.2 to 73%. Eleven of the 12 studies reported mostly an increase in stroke hospitalisations during the pandemic period compared to the pre-pandemic period or observed no changes. In the single study by Wadhera et al. which evaluated CVD deaths in the USA [
      • Wadhera R.K.
      • Shen C.
      • Gondi S.
      • Chen S.
      • Kazi D.S.
      • Yeh R.W.
      Cardiovascular deaths during the COVID-19 pandemic in the United States.
      ], deaths caused by ischemic heart disease and hypertensive disease increased nationally after the onset of the pandemic in 2020, compared with changes over the same period in 2019, but not for HF, cerebrovascular disease, or other diseases of the circulatory system.

      3.5 Severity of presentation

      The severity of presentation on hospitalisation was reported by 26 studies (Table 2). Most studies (n = 15) reported that presentation was severe during the pandemic period compared to the pre-pandemic period. A variety of presentations were reported which included higher cardiac enzymes and worse left ventricular ejection fraction for ACS patients, higher admission National Institutes of Health Stroke Scale (NIHSS) scores for stroke patients, higher rates of New York Heart Association (NYHA) III or IV symptoms and severe peripheral oedema for HF patients and higher prevalence of risk factors associated with poorer prognosis in stroke or HF patients. Eleven studies reported no differences in severity of presentation comparing the two periods.

      3.6 Management on hospitalisation

      Thirty-six studies reported data on procedures performed during hospitalisation (Table 3). The majority of studies (n = 20) reported that less cardiovascular procedures were performed during the pandemic compared to the pre-pandemic periods. Procedures reported included coronary angiographies, PCI and thrombolysis for ACS patients and magnetic resonance imaging, acute revascularization treatments, thrombolysis and thrombectomies for stroke. Fifteen studies reported no differences in these procedures between the periods compared. Only one study reported that stroke patients admitted during the pandemic period were more likely to undergo intravenous thrombolysis and mechanical thrombectomy.
      Table 3Management, patient- and system-related delays and outcomes.
      Author, year of publicationManagementPatient- and system-related delaysReasons for delays in seeking medical careLength of stayOutcomes related to management
      Araiza-Garaygordobil, 2021Significant reduction of patients undergoing pPCI was observed (81.8% pre-pandemic vs. 76.2% pandemic, difference: −5.6%, p = 0.041).The proportion of patients who developed any mechanical complication during the pandemic period was higher when compared with the pre-pandemic period (1.98% [23/1161] vs. 0.98% [41/4143], p = 0.006) and compared to the historical control (1.98% [23/1161] vs. 1.17% [30/2547], p = 0.057)
      Mafham, 2020There were reductions in the number of PCI procedures for patients with both STEMI (438 PCI procedures per week in 2019 vs 346 by the end of March, 2020; percent reduction 21%) and NSTEMI (383 PCI procedures per week in 2019 vs 240 by the end of March, 2020; percent reduction 37%).The median length of stay among patients with ACS fell from 4 days (IQR 2–9) in 2019 to 3 days (1–5) by the end of March, 2020.No apparent change in in-hospital mortality among patients admitted with ACS in the period
      Perrin, 2020Delay from symptom onset to first medical contact was longer among patients suffering from STEMI in the COVID-19 period compared with the control period (112 min vs 60 min, p = 0.049). Delayed presentations were reported in 18.2% and 9% of patients in the COVID-19 and control periods, respectively (p = 0.3)ACS patients delayed their call to the emergency services mainly because of fear of contracting or spreading COVID-19 following hospital admission, as well as of adding burden to the healthcare systemHospital length of stay was significantly shorter for the COVID-19 period as compared to the control period (6 vs 7 days, p = 0.03).
      Tam, 2020Delay from symptom onset to first medical contact was longer among patients suffering from STEMI in the COVID-19 period compared with the pre-pandemic period. The proportion of patients who presented out of the revasculrization window during the pandemic period was higher when compared with the pre-pandemic period (33% vs 27.8%)The primary composite outcome of in-hospital death, cardiogenic shock, sustained ventricular tachycardia or fibrillation and use of mechanical circulatory support was significantly higher during the pandemic period compared to pre-pandemic period (29.7% vs 14.1%, p = 0.02)
      Toniolo, 2020
      Huet, 2020
      Kwok, 2020bCompared with 2017–2019, patients admitted with primary PCI for STEMI in the month of April 2020 were more likely to have longer time from symptom-to-hospital (median 135 min vs 153 min, p = 0.004) and they also had a longer door-to-balloon time (48 (21–112) vs 37 (16–94) min, p < 0.001).There was a shorter median length of stay postlockdown compared to prelockdown: 2 (1–3) days vs 3 (2−4) days, p < 0.001).No significant differences in in-hospital death and MACE were observed overall
      Boukhris, 2020There was increase in patients with >2 h delays in the setting of STEMI in the pandemic period compared to the same period in 2019. Delays in ischemic strokes were similar between the two periods
      Braiteh, 2020In NSTEMI patients, 36.4% presented late (>24 h of symptoms) during the COVID-19 pandemic in comparison with 2019 (27.1%, p = .033).
      Butt, 2020Overall length of stay was shorter during the pandemic period compared to March 2019.Deaths - Compared to March 2019 (179), there was 19% increase in in-hospital deaths in March 2020 (221) (p = 0.05)
      De Filippo, 2020
      De Rosa, 2020Both patient- and system-related declared delays were substantially increased during the COVID-19 outbreak. Time from symptom onset to coronary angiography was increased by 39.2% in 2020 compared with the equivalent week in 2019, while the time from first medical contact to coronary revascularization was increased by 31.5%.Case fatality rate during the pandemic was increased compared with 2019.
      Fileti, 2020Among those admitted for ACS, 57 (79.1%) were treated with PCI in 2020, and 67 (71.2%) in 2019, with an overall 14.9% reduction.Among STEMI patients, the rate of those with a time delay presentation from symptoms onset longer than 180 min was significantly higher during the pandemic period compared to 2019PCI procedural success and in-hospital mortality were not significantly different between the two periods
      Folino, 2020
      Haddad, 2020Longer delays between symptom onset and first medical contact were noted during the pandemic compared to pre-pandemic and control periodThere were worse in-hospital outcomes (MACE, mechanical complications, death, other cardiac complications) during the pandemic compared to pre-pandemic and control period
      Hauguel-Moreau, 2020Median symptom-onset-to-first medical contact time was significantly higher in 2020 than in the two previous years (600 min [298–632] versus 121 min [55–291], p < 0.001). There was also a delay in STEMI management (3-fold increase in ischemic time)
      Holy, 2020
      Metzler, 2020
      Montagnon, 2021For patients with ACS, the average time interval between the first symptoms and the consultation was shorter in 2020. However, the average time lapse between the consultation and subsequent cerebral imaging increased in 2020 compared with 2019.
      Showkathali, 2020The symptom to door time was prolonged in 2020 compared to 2019The duration of hospital stay was longer in 2020 compared to previous yearsThere was no difference in in-hospital mortality between the two study periods of 2020 and 2019 respectively
      Sokolski, 2020The mean length of stay was significantly shorter in 2020 (4.9 days) in comparison to 2019 (5.9 days)There was no statistically significant difference in death rates between studied periods: 107 (3.6%) in 2020 versus 175 (3.9%) deaths in 2019
      Solomon, 2020
      Vacanti, 2020The total number of coronary angiographies and PCIs were lower in 2020 compared to 2019 and 2019
      Yalamanchi, 2020The in-hospital mortality of patients was also similar in all 3 years
      Tsioufis, 2020
      Gasior, 2020
      Dreger, 2020Number of PCI in AMI patients also fell.
      Anderson, 2020
      Gluckman, 2020Median length of stay for patients with AMI was shorter in the early COVID-19 period by 7 h and in the later COVID-19 period by 6 h compared with the before period. Similar trends were observed for STEMI and NSTEMIPatients with STEMI had a statistically greater risk of mortality during the later COVID-19 period
      Mohammad, 2020PCI was equally performed during the two periodsTime from symptom onset to PCI was shorter during the pandemic compared to the control periodNo differences in all-cause mortality rates between the two periods
      Piccolo, 2020
      Secco, 2020Longer door-to-balloon and symptoms to PCI times in 2020 compared to 2019No difference in in-hospital mortality between the two periods. However, in 2020, patients had a lower discharged residual left ventricular function and an increased predicted late cardiovascular mortality
      Ayad, 2021Time from first medical contact to needle was longer during the pandemic period.Hospital length of stay was longer during the pandemicIn-hospital mortality, incidence of re-infarction and need for revascularization were higher during the pandemic period. Incidence of HF, stroke and bleeding was not different between the periods
      Bhatt, 2020Hospital length of stay was shorter in March 2020: 4.8 (2.4−8.3) days compared with March 2019: 6.0 (3.1−9.6) daysIn-hospital mortality was not significantly different between the two periods
      Daoulah, 2021Timing from the onset of symptoms to the balloon of more than 12 h was higher during 2020 comparing to pre-COVID 19No differences in length of hospital stayThere were no differences with respect to in-hospital events (mortality, thrombosis, bleeding etc)
      Desai, 2020Number of patients undergoing endovascular thrombectomy remained constant
      Diegoli, 2020No differences in number of patients provided with reperfusion therapiesNo differences in time from onset to admission.
      Gitt, 2020
      Hammad, 2020Door-to-balloon time were not significantly different(i) Fear of contracting COVID-19 (27%); (ii) Symptoms were COVID-19 related (18%); (iii) Did not want to burden the emergency dept (9%)Shorter ICU duration and length of stay during the pandemic period: 2.3 vs 3.6 days
      Kerleroux, 2020There was a significant increase in delays between imaging and groin puncture during the pandemic periodNo difference in outcomes (successful reperfusion and in-hospital mortality)
      Montaner, 2020Time from symptoms onset to arrival at hospital was delayed during the pandemic period. Door-to-needle time was delayed during the pandemic. However, mean times of arrival to thrombectomy reference center from symptoms onset improved during the pandemic
      Neves Briard, 2020Time from symptom onset to hospital presentation was longer during the pandemic period. Door-to-needle and door-to-recanalization metrics were also longer during the pandemic. A significantly smaller proportion of ischemic stroke patients was treated with thrombolysis or thrombectomy during the pandemic
      Pop, 2020There were 33.3% fewer acute revascularization treatments, 40.9% less intravenous thrombolysis and 27.6% less mechanical thrombectomy in 2020No significant differences in patient- and system-related delays.
      Popovic, 2020Delayed hospital presentation in the pandemic period compared to control periodHigher in-hospital mortality in the pandemic period
      Range, 2020Time from symptom onset to first medical contact was longer for lockdown groupLength of hospital stay was similar in both periodsThere were higher rates of in-hospital MACE and mortality in the lockdown group but the differences were not significant.
      Reinstadler, 2020Door-to-balloon times were constant during the period. Total ischemic times increased from 164 min (calendar week 9/10) to 237 min (calendar week 11/12) and to 275 min (calendar week 13/14) (p = 0.006).Rates of in-hospital death and re-infarction were similar between groups
      Sarfo, 2020Case fatality rate during the pandemic was increased compared with 2019.
      Teo, 2020Stroke onset-to-door arrival time was longer during the pandemic. There were no significant differences in the ambulance scene arrival to hospital arrival time, proportion of patients receiving reperfusion therapy, door-to-needle time, and mechanical thrombectomy procedural times during the 2 periods
      Toner, 2020Symptom-to-door time was longer during the COVID-19 period (4-fold increase). Proportion of patients presenting late was also higher during the pandemic period.
      Abdelaziz, 2020Delay in symptom-to-first medical contact during pandemic vs pre-COVID era. The door-to-balloon time was similar between both groups.
      Agarwal, 2020The time from symptom onset to presentation was not significantly different the two groups. There were longer median door to head CT and door to groin puncture times during the pandemic compared to pre-pandemic times. Time to alteplase administration, door to reperfusion times and defect-free care were similar in the pandemic and pre-pandemic groupsThere was no difference in the length of hospital stay between the pandemic and pre-pandemic cohortsSuccessful recanalization rates were similar between the two groups. Pandemic patients had increased discharge mortality in multivariable analysis compared to pre-pandemic patients
      Burgos, 2020
      Aldujeli, 2020NSTEMI: The median pain-to-door time was longer during the pandemic compared to pre-pandemic era. There was a significant delay in door-to-reperfusion time during the pandemic. There were 24 (80%) and 25 (42%) patients who presented after 12 h of pain onset in pandemic and pre-pandemic eras, respectively (p = 0.0006). STEMI: The median pain-to-door time during the pandemic was longer than that of the pre-pandemic. There were 22 (47%) and 14 (24%) patients who presented after 12 h of pain onset in the pandemic and prepandemic eras, respectively (p = 0.0127). There was no difference in delay in door-to-reperfusion time.There were no differences in length of hospitalization between pandemic and pre-pandemic eras.There were no differences in in-hospital death, or stroke between pandemic and pre-pandemic eras.
      Andersson, 2020Mortality was similar before and after the national lockdown for the population with HF
      Ball, 2020
      Boeddinghaus, 2020220/398 PCIs (55.3%) PCIs were performed before versus 178/398 PCIs (44.7%) after the outbreak.Time from chest pain onset to ED presentation, postinfarction LVEF, and median door-to-balloon time remained unchanged.
      Bromage, 2020There were no differences in inpatient management, including place of care and pharmacological management of heart failure with reduced ejection fractionIn-hospital mortality rates were low in both periods
      Bryndza, 2021There was a significant increase (90.7%) in the number of patients who experienced pain longer than 12 h prior to presentation to the hospitalThere was a 100% increase in mechanical complications during pandemic period compared to control period
      Cammalleri, 2020In March 2020, there was longer median time in symptom-to-first medical contact, spoke-to-hub, and the cumulative symptom-to-wire delay compared to March 2019Length of hospitalization was longer in 2020Procedural data and in-hospital outcomes were similar between the 2 groups. Patients in 2020 had a worse left ventricular ejection fraction at discharge.
      Candelaresi, 2021Compared to the pre-lockdown, there was a significant reduction in the number of acute reperfusion treatments for stroke.The time to reach medical attention was significantly longer in the lockdown phase. For patients who underwent acute reperfusion treatment, there was a significantly longer time-to-imaging and a trend to longer time-to-needle (75 versus 90 min P 0.23), but not time-to-groin.Discharge neurological status was not significantly different between the periods
      Chew, 2021Fewer patients in the pandemic group achieved door-to-baloon time <90 min compared with the pre-pandemic group.There was no difference in hospital admission duration between groups.In-hospital mortality was similar between groups. The 30-day readmission rate was lower in the pandemic group compared with the pre-pandemic group. The rates of sepsis and acute mitral regurgitation were higher in the pandemic group compared with the pre-pandemic group.
      Choudhary, 2020Percentage of STEMI patients undergoing emergent catheterisation was lower in the lockdown and pre-lockdown period compared to pre-COVID period. Percentage of STEMI patients having thrombolysis was higher in the lockdown and pre-lockdown period compared to pre-COVID period.The percentage of STEMI patients who presented outside the window period (presentation after 12 h of symptom onset) was 6.1% in the pre-COVID period, 17.4% during the pre-lockdown period and 25.0% during the lockdown period.In-hospital mortality was 7.3%, 3.5% and 2.7%, in the lockdown, pre-lockdown, and pre-COVID periods, respectively.
      Çinier, 2020Prolonged ischemic time, longer pain-to-balloon and door-to-balloon time during the pandemic.
      Colivicchi, 2020In-hospital all-cause mortality was 17.2% in 2020 and 6.3% in 2019
      Cummings, 2020There was a higher percentage of patients receiving intravenous tPA during the pandemic, and the number of thrombectomies per week was lower during the pandemicNo differences in door-to-needle and door-in-door-out timesNo differences in in-hospital mortality
      Del Pinto, 2020Less daily cardiovascular procedures performed in 2020 than in 2019More in-hospital cardiovascular deaths occurred in 2020 compared with 2019. Less in-hospital all-cause mortality occurred in 2020 than 2019
      Enache, 2020
      Erol, 2020There was a significant reduction in the overall frequency of coronary angiography during the pandemic period compared to the pre-pandemic period. Frequency of PCI decreased during the pandemic.EMS transport significantly increased during the pandemic period. Median time from symptom-onset to hospital-arrival was increased during the pandemic. The total ischemic time for patients with STEMI who were treated with PCI was significantly longer during the pandemic period compared with the pre-pandemic period. Door-to-balloon time was similar in the two periods.In-hospital major adverse cardiac events were significantly increased during the pandemic period
      Frisullo, 2020Significant reduction of the total number of thrombolysis and a non-significant increase of thrombectomy during the pandemicSignificant increase in onset-to-door time and door-to-groin time during pandemicSignificant reduction in length of hospitalization during pandemic
      Giannouchos, 2021
      Hoyer, 2020There was a significant drop in the thrombolysis rate by 60% and in the thrombectomy rate by 61% during the pandemic in one of the centers
      Hsiao, 2020Reperfusion treatments also appeared to decline by 31% and specifically thrombolysis by 33%
      JF Huang, 2020Recommendation for acute stroke intervention (IV-tPA and/or thrombectomy) occurred at a lower rate for our postepandemic declaration groupThe last known normal/symptom onset time to telestroke activation in the ED was significantly shorter for the postepandemic declaration group
      Ikenberg, 2020There was no difference of daily numbers of patients receiving thrombolysis and thrombectomy
      Jasne, 2020No difference in rate of Thrombolysis in Cerebral Infarction 2b or greater revascularizationThere was no difference in time to presentation, door-to-needle and door-to-reperfusion timesNo difference in median length of stayThere was no difference in discharge modified Rankin Scale.
      John, 2020Ischemic stroke: The rate of treatment with intravenous thrombolysis was similar in both years; Haemorrhagic stroke: Surgical treatment including placement of an external ventricular drain, endovascular embolization and microsurgical clipping/resection or hematoma evacuation occurred at similar rates.Ischemic stroke: Presentation to the hospital from last known well time and door-to-needle times for intravenous thrombolysis was similar. However, door-to-groin puncture times for endovascular thrombectomy was significantly longer in 2020.There was no difference in in-hospital mortality, discharge disposition or discharge/30-day modified Rankin Score
      Kobo, 2020Patients admitted in 2020 had greater likelihood of door-to-balloon times> 90 min and greater likelihood of pain-to-balloon times> 12 hPatients admitted in 2020 had longer hospital stayPatients admitted in 2020 experienced higher rates hemodynamic instability and fewer early (<72 h) discharge
      Kuitunen, 2020
      Lauridsen, 2020The proportion of patients who underwent CAG, PCI, CABG, and extra corporeal membrane oxygenation (ECMO) were similar between 2015 and 2019 and 2020 during lockdownNo difference in 7-day mortality was observed between study periods.
      Little, 2020Aspiration thrombectomy and rates of cases completed with TIMI flow less than 3 were similar between both groupsThere was no significant difference in pain to first call for help or door-to-balloon. There was longer ambulance response times in 2020 than in 2019.Length of stay was similarThere was no significant difference in ICU admission or in-hospital all-cause mortality
      Nagamine, 2020The average last known well to arrival time for stroke codes was longer in 2020 than in 2019. Mean time from patient arrival to administration of tPA (door-to-needle) was similar for both periods. Mean time from patient arrival to vessel puncture for endovascular therapy (door to puncture) was shorter in 2020 compared to 2019.In-hospital mortality was higher in 2020 than in 2019
      Mitra, 2020Median time from symptom onset to presentation was shorter in 2020 compared to 2019. Proportion of patients who presented >12 h after onset of symptoms were similar in both periods. Median time to primary reperfusion intervention was longer in 2020 compared to 2019.No differences in hospital length of stayThere were no differences in mortality at hospital discharge
      Nguyen-Huynh, 2020The percentage of patients receiving alteplase was not significantly different.Median door-to-needle time among noncanceled stroke alerts was unchanged. The median times from LTKW-to-needle time or alteplase treatment time were not significantly different.Length of stay was similarStroke discharges decreased significantly post lockdown compared with pre-lockdown. No difference in in-hospital mortality
      Oseran, 2020
      Paliwal, 2020Proportion of activations receiving acute recanalization therapy remained stable.In patients undergoing acute intervention, door-to-activation and door-to-neurologist review time were longer during the lockdown compared to pre-lockdown. Symptom-to-door-time was similarFor patients that received acute recanalization therapy, early neurological outcomes in terms of change in median NIHSS at 24 h were largely similar
      Papafaklis, 2020There was no difference in the rate of cardiac deaths between the two periods, while the rates of in-hospital repeat MI and stent thrombosis were numerically higher during the COVID-19
      Piuhola, 2020
      Rashid Hons, 2020The overall rates of invasive coronary angiography were significantly lower during COVID-19 period. The use of PCI was also lower across COVID-19 months in 2020 compared with pre–COVID-19 months in 2019. Patients admitted during the COVID-19 period were slightly less likely to be seen by a cardiologistIncreased time to reperfusion in STEMI patients during the COVID-19 periodIncreased in-hospital mortality during the COVID-19 period
      Richter, 2021IVT rate in patients with stroke was comparable, whereas mechanical thrombectomy rate was significantly higher during the pandemicIn-hospital mortality was significantly increased in patients with stroke during the pandemic period
      Rodríguez-Leor, 2020There were no differences in reperfusion strategy (> 94% treated with primary PCI in both groups)Patients treated with primary PCI during the COVID-19 outbreak had a longer ischemic time but showed no differences in the time from first medical contact to reperfusion.In-hospital mortality was higher during the COVID-19 period
      Ruparelia, 2020
      Schirmer, 2020The mean interval from last-known-well to the presentation was significantly longer in the COVID period
      Seiffert, 2020The percentage of patients treated with interventional or open-surgical procedures remained similar over timeIn-hospital mortality in hospitalizations for stroke increased from pre-COVID to COVID
      Sharma, 2020There was no difference in time from symptom onset to hospital arrival.
      Siegler, 2020Fewer brain MRIs were performed during the COVID-19 period when compared to pre-COVID-19There was no significant delay from the time patients were last known well to ED arrival, arrival to computed tomography scan or to thrombolysis.Patients treated during COVID-19 had a shorter hospital length of stay when compared to patients admitted during the pre-COVID-19 period: 2.5 (2–7) vs 4 (2−8)No difference in in-hospital mortality
      Tejada Meza, 2020There were no differences in the proportion of patients undergoing intravenous and endovascular treatments proceduresIn-hospital mortality of stroke patients increased significantly
      Uchino, 2020Thrombolysis decreased during the COVID-19 period but thrombectomy remained unchangedTime to presentation and time to treatment were unchanged. Door-to-needle, CT completion and puncture times were unchanged.
      Vensentini, 2020
      Wadhera, 2021
      J Wang, 2020Patients admitted during the COVID-19 pandemic were more likely to undergo intravenous thrombolysis and mechanical thrombectomyThere were no differences in patients’ disposition including home, short-term, and longterm facility
      Yang, 2020Onset to hospital arrival was not different. The time from hospital arrival to puncture and time from hospital arrival to reperfusion were significantly prolonged in the pandemic group compared with the pre-pandemic group.The rate of successful reperfusion was not significantly different between the two groups
      Zhao, 2020The total number of thrombolysis and thrombectomy cases dropped by 26.7% and 25.3%, respectively, in 2020Patients’ and their families’ fear of contracting virus in hospital (87.2%); Insufficient transportation resources (43.2%); Lack of first aid knowledge (42.3%); Lack of family support (31.7%); Insufficient ambulance resources (15.4%)
      Cox, 2020No difference in length of stayIn-hospital mortality rate was not different between the two periods

      3.7 Patient- and system-related delays

      Fifty-five studies reported on patient- and health system-related delays during presentation and management (Table 3). The majority of studies (n = 37) reported more patient- and health system-related delays during the pandemic compared to pre-pandemic times. The most common patient-delay was a longer delay between symptom onset and first medical contact. The longest delay was a median of 10 h for symptom onset to first medical contact for an acute coronary syndrome during the pandemic compared to a median of about 2 h pre-pandemic (600 min [298–632] versus 121 min [55–291], p < 0.001) [
      • Hauguel-Moreau M.
      • Pillière R.
      • Prati G.
      • Beaune S.
      • Loeb T.
      • Lannou S.
      • et al.
      Impact of Coronavirus Disease 2019 outbreak on acute coronary syndrome admissions: four weeks to reverse the trend.
      ].
      Other measures of delay that were reported included: delays in emergency transport, longer time from symptom onset to consultation and intervention (coronary angiography, PCI, reperfusion or thrombectomy), larger proportion of patients presenting outside of the revascularization window, increase in ischemic time, longer symptom-to-door time, longer medical contact to needle, longer door-to-balloon time, and longer door-to-needle time. Fifteen studies reported no significant differences in patient- and system-related delays. Only three studies reported shorter times between symptom onset and consultation or PCI procedure during the pandemic compared to the pre-pandemic periods.

      3.8 Reasons for delays in seeking medical care

      Only three studies were identified to have assessed the reasons patients provided for their delay in seeking medical care (Table 3). The main reasons provided was because of the fear of contracting COVID-19 in hospital as well as adding extra burden to the healthcare system.

      3.9 Length of stay

      Twenty-four studies reported data on length of hospital stay (Table 3). Of this number, 10 studies reported a shorter length of stay during the pandemic period (1–8 days) compared with the pre-pandemic period (2–12 days); 10 reported no difference in length of stay between the two periods; and 4 reported a longer length of stay during the pandemic period.

      3.10 Outcomes related to management

      Fifty-four studies reported outcomes related to management (Table 3). The majority of studies (n = 31) reported no change in in-hospital mortality or discharge disposition among hospitalised patients comparing the pandemic period with pre-pandemic times. Twenty-three studies reported an increase in worse in-hospital outcomes (major adverse cardiac events (MACE), stroke, cardiac and mechanical complications and the need for revascularisation) and in-hospital death during the pandemic compared to the pre-pandemic period.

      4. Discussion

      4.1 Key findings

      Using systematic review methodology, we have assessed the indirect impact of COVID-19 on hospitalisations for cardiometabolic conditions and their management. Based on 103 studies conducted in more than 34 countries across six continents, our results demonstrated the following: (i) the majority of studies had evaluated trends in hospitalisations for ACS followed by acute strokes and HF, with only two studies on hypertension and diabetes; (ii) majority of studies reported declines in hospitalisations during the pandemic compared to pre-pandemic times, with the reductions ranging from 20.2 to 73% and the results were not suggestive of age-specific and gender-related declines; (iii) severe presentation, less utilization of cardiovascular procedures such as coronary angiographies and PCI, and longer patient- and healthcare-related delays were common during the pandemic; (iv) the fear of contracting COVID-19 was the main reason patients provided for the delay in seeking medical care; (v) most studies reported shorter length of hospital stay during the pandemic or no difference in length of stay; and (vi) finally, the majority of studies reported no change in in-hospital mortality among hospitalised patients comparing the pandemic period with pre-pandemic times.
      We identified only one relevant systematic review which assessed the extent to which health services related to the care and management of acute cardiovascular events had been impacted during the COVID-19 pandemic. Kiss and colleagues in a review of 27 studies reported a decrease in stroke and ACS admissions (declines ranging from 12 to 50%) during the COVID-19 period compared to non-COVID-19 periods, a decrease in number of reperfusion procedures, a shortening in the lengths of hospital stay, and longer symptom-to-door times [
      • Kiss P.
      • Carcel C.
      • Hockham C.
      • Peters S.A.
      The impact of the COVID-19 pandemic on the care and management of patients with acute cardiovascular disease: a systematic review.
      ]. Whiles the authors only evaluated acute cardiovascular conditions, we adopted a broader approach and focused on all cardiometabolic conditions and evaluated other outcome measures such as severity of presentation, utilization of cardiovascular procedures, both patient and system-related delays, reasons provided by patients for delays in seeking care, and outcomes related to management such as complications, in-hospital mortality and discharge disposition. We have also identified some gaps in the evidence. None of the studies provided specific guidance on how the adverse impact of the pandemic on patients’ health-seeking behaviour and response of health systems could be mitigated.
      As expected, infectious disease outbreaks have the potential to cause volume changes in emergency department attendances and hospitalisations. These changes have been witnessed in previous epidemics and pandemics such as the 2003 severe acute respiratory syndrome (SARS) outbreak [
      • Huang C.
      • Yen D.H.
      • Huang H.
      • Kao W.
      • Wang L.
      • Huang C.
      • et al.
      Impact of severe acute respiratory syndrome (SARS) outbreaks on the use of emergency department medical resources.
      ], the 2009 novel influenza A (H1N1) pandemic [
      • Fagbuyi D.B.
      • Brown K.M.
      • Mathison D.J.
      • Kingsnorth J.
      • Morrison S.
      • Saidinejad M.
      • et al.
      A rapid medical screening process improves emergency department patient flow during surge associated with novel H1N1 influenza virus.
      ,
      • Miroballi Y.
      • Baird J.S.
      • Zackai S.
      • Cannon J.
      • Messina M.
      • Ravindranath T.
      • et al.
      Novel influenza A (H1N1) in a pediatric health care facility in New York City during the first wave of the 2009 pandemic.
      ] and the 2015 Middle East respiratory syndrome (MERS) outbreak [
      • Lee S.Y.
      • Khang Y.H.
      • Lim H.K.
      Impact of the 2015 Middle East Respiratory syndrome outbreak on emergency care utilization and mortality in South Korea.
      ]. The unprecedented surge in COVID-19 infection rates and associated substantial morbidity and mortality rates across the globe led policy makers to institute several containment measures ranging from social distancing to lockdowns, to mitigate the disease. Obviously, these measures came at a cost as they impacted on patients’ health-seeking behaviors’ and the delivery of health services. Several reasons could explain the decline in hospitalisations for cardiometabolic conditions, especially the acute ones. The major reason being the reluctance of patients and their families to initiate medical contact to avoid exposure to COVID-19, as evaluated and reported by three of the included studies in the present review. Other potential reasons include patients not wanting to burden the health system; lack of family support; insufficient ambulance support due to the pressure on the health system and lack of adequate personnel; and restructuring of the healthcare system in response to the pandemic which involved increased hospital capacity for patients infected with COVID-19 and deferral or cancellation of nonessential procedures, routine patient visits and diagnostic evaluations. Despite these reasons, we found that among hospitalised patients, comparing the pandemic period with pre-pandemic times no change in in-hospital mortality was observed. This may suggests that once in the hospital, the care patients received for cardio-metabolic conditions was not compromised. Patients suffering acute cardio-metabolic conditions are not therefore to be encouraged to seek medical help.
      It is possible the stay-at-home campaigns by governments and the constant information provided by the media were alarming enough for patients to delay seeking medical care [
      • Moroni F.
      • Gramegna M.
      • Ajello S.
      • Beneduce A.
      • Baldetti L.
      • Vilca L.M.
      • et al.
      Collateral damage: medical care avoidance behavior among patients with myocardial infarction during the COVID-19 pandemic.
      ,
      • Wessler B.S.
      • Kent D.M.
      • Konstam M.A.
      Fear of coronavirus disease 2019—an emerging cardiac risk.
      ]. Even though out-of-hospital mortality is out of the scope of this review, it is not inconceivable that this could have been adversely affected as a result of the stay-home-messaging. Three studies conducted in France, United Arab Emirates (UAE) and Ghana observed an increase in stroke hospitalisations during the pandemic, which could be attributed to an increasing burden of stroke and the fact that the COVID-19 pandemic was not severe especially in Ghana and the UAE. Increased severity at presentation during the pandemic period compared to the pre-pandemic period is likely related to the delays in seeking medical care, effects of the social restrictions such as loneliness, stress, depression, mental health issues and physical inactivity [
      • Holt-Lunstad J.
      • Smith T.B.
      • Baker M.
      • Harris T.
      • Stephenson D.
      Loneliness and social isolation as risk factors for mortality: a meta-analytic review.
      ,
      • Lima C.K.T.
      • de Medeiros Carvalho P.M.
      • de Araújo Araruna Silva Lima I.
      • de Oliveira Nunes J.V.A.
      • Saraiva J.S.
      • de Souza R.I.
      • et al.
      The emotional impact of Coronavirus 2019-nCoV (new Coronavirus disease).
      ,
      • Redfors P.
      • Isaksén D.
      • Lappas G.
      • Blomstrand C.
      • Rosengren A.
      • Jood K.
      • et al.
      Living alone predicts mortality in patients with ischemic stroke before 70 years of age: a long-term prospective follow-up study.
      ]. Less utilization of cardiovascular procedures, healthcare system delays for procedures and shorter lengths of hospital stay during the pandemic period are likely due to the pressure on healthcare systems, shortage of health personnel because of sickness due to COVID-19 and early discharges to avoid too much exposure in the hospital environment.
      These findings have several implications for both patient care and healthcare systems all over the world, given that cardiovascular conditions account for substantial morbidity and over 17 million deaths each year, being the leading cause of mortality in the world [
      • Mann D.L.
      • Zipes D.
      • Libby P.
      • Bonow R.
      Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine.
      ]. As we come out of the pandemic, preparations for delivering services for cardiovascular diseases needs to take these findings into consideration. The findings should also inform preparations for future pandemics. The declines in hospitalisations for acute cardiovascular conditions are irrespective of age and sex and largely due to fear of contracting COVID-19. This has also been fueled by media and anecdotal reports about patients contracting COVID-19 in the hospital. While there is some truth to this, patients need to be educated on the need to seek medical help promptly and adopt healthy lifestyles in the areas of nutrition and physical activity. Furthermore, given that the decrease in hospitalisations and delays in management could also be due to the adaptations of healthcare systems in response to the pandemic, further restructuring needs to be done to maintain high standards of care and also prepare for future pandemics of this nature.

      4.2 Strengths and limitations

      There are several strengths and limitations of this study that deserve consideration. Compared to the only relevant previous review on the topic [
      • Hauguel-Moreau M.
      • Pillière R.
      • Prati G.
      • Beaune S.
      • Loeb T.
      • Lannou S.
      • et al.
      Impact of Coronavirus Disease 2019 outbreak on acute coronary syndrome admissions: four weeks to reverse the trend.
      ], our review was more comprehensive and focussed on cardiometabolic conditions and a wide range of measures related to the management of patients. Our literature search was detailed and spanned multiple databases, yielding over 100 articles conducted across 6 continents. The findings may be generalisable globally given that the findings were based on data across 6 out of 7 continents. Though there were a number of limitations, these were all inherent to the included studies and not the actual review. The outcome measures were heterogenous and not consistently reported, hence we were unable to conduct any meta-analysis as originally planned in our published protocol (CRD42021236102). However, we were able to summarise the evidence according to identified consistent themes using narrative synthesis and tables. The findings reported by included studies were based on a diversity of observational study designs which were generally not of high methodological quality. The pandemic and pre-pandemic periods utilised were not consistent across studies, hence it is challenging to make any head-to-head comparisons. Only three out of the 103 studies formally assessed the reasons patients provided for their delay in seeking medical care. Given these limitations, the findings should be interpreted with caution.

      5. Conclusion

      Data based on available real-world evidence clearly indicates that health-seeking behaviour of patients for cardiometabolic conditions (particularly the acute ones), their management and outcomes have been adversely impacted by the COVID-19 pandemic. Though the pandemic seemed to have adversely impacted on the management of patients, in-hospital mortality rates were not significantly affected as reported by the majority of studies. None of the studies provided specific guidance on how the adverse impact of the pandemic on patients’ health-seeking behaviour and response of health systems could be mitigated. Patients should be educated via population-wide approaches on the need for timely medical contact and health systems should put adequate response strategies in place to provide timely care to patients at high risk and also manage future outbreaks of infectious disease.

      Data sharing

      The corresponding author had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. This study is based in data from published articles.

      Authors contribution

      Samuel Seidu: Literature search, data collection, study design, data interpretation, writing.
      Setor K. Kunutsor: Literature search, data collection, analysis, data interpretation, writing.
      Xavier Cos: Data interpretation, writing, editing.
      Kamlesh Khunti: Study design, literature search, data interpretation, writing.

      Funding

      This study was supported with a research grant from Primary Care Diabetes Europe (PCDE) . PCDE as a society, has received sponsorship from Novo Nordisk, Eli Lilly and Roche Diagnostics, but the companies had no input in the study.

      Declarations of interest

      None.

      Appendix A. Supplementary data

      The following are Supplementary data to this article:

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