Clinical presentation, disease course and outcome of COVID-19 in hospitalized patients with and without pre-existing cardiac disease – a cohort study across eighteen countries

Aims Patients with cardiac disease are considered high risk for poor outcomes following hospitalization with COVID-19. The primary aim of this study was to evaluate heterogeneity in associations between various heart disease subtypes and in-hospital mortality. Method and results We used data from the CAPACITY-COVID registry and LEOSS study. Multivariable Poisson regression models were fitted to assess the association between different types of pre-existent heart disease and in-hospital mortality. 16,511 patients with COVID-19 were included (21.1% aged 66 – 75 years; 40.2% female) and 31.5% had a history of heart disease. Patients with heart disease were older, predominantly male and often had other comorbid conditions when compared to those without. Mortality was higher in patients with cardiac disease (29.7%; n=1545 versus 15.9%; n=1797). However, following multivariable adjustment this difference was not significant (adjusted risk ratio (aRR) 1.08 [95% CI 1.02 – 1.15; p-value 0.12 (corrected for multiple testing)]). Associations with in-hospital mortality by heart disease subtypes differed considerably, with the strongest association for heart failure aRR (1.19 [1.10 – 1.30]; p-value <0.018) particularly for severe NYHA III/IV) heart failure (aRR 1.41 [95% CI 1.20 – 1.64; p-value <0.018]. None of the other heart disease subtypes, including ischemic heart disease, remained significant after multivariable adjustment. Serious cardiac complications were diagnosed in <1% of patients. Conclusion Considerable heterogeneity exists in the strength of association between heart disease subtypes and in-hospital mortality. Of all patients with heart disease, those with heart failure are at greatest risk of death when hospitalized with COVID-19. Serious cardiac complications are rare. ### Competing Interest Statement The following authors report support in the context of the present manuscript: Asselbergs FW: The University Medical Center Utrecht received grant funding from the Dutch Heart Foundation for conducting the CAPACITY-COVID registry (2020B006 CAPACITY). Kopylov PY: Sechenov University received funding by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Center Digital Biodesign and Personalized Healthcare: No. 075-15-2020-926. Linschoten M: Reports support by the Alexandre Suerman Stipend of the University Medical Center Utrecht. McCann GP: Received grant funding as co-applicant for COVID Heart and PHOSP COVID research studies. Pilgram L: Received grant funding from the Willy Robert Pitzer Foundation during the conduct of the LEOSS registry study. Schut A: Werkgroep Cardiologische Centra Nederland (WCN), a partner within the CAPACITY-COVID consortium, has received funding from the Dutch Heart Foundation (2020B006 CAPACITY) for site management and logistic support in the context of the CAPACITY-COVID registry in the Netherlands. Shore AC: Received grant funding from the National Institute of Health Research for Exeter Clinical Research facility during the conduct of the study. ### Funding Statement This work was supported by the Dutch Heart Foundation (2020B006 CAPACITY), the EuroQol Research Foundation, Novartis Global, Novo Nordisk Nederland, Servier Nederland and Daiichi Sankyo Nederland (CAPACITY-COVID) and the German Centre for Infection Research (DZIF) and the Willy Robert Pitzer Foundation (LEOSS). The work of Philippe Kopylov and Daria Gognieva was financed by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of World-Class Research Center Digital biodesign and personalized healthcare no. 075-15-2020-926. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The ethics entity of the lead center of CAPACITY-COVID (Medical Research Ethics Committee Utrecht) deemed that the Medical Research Involving Human Subjects Act (WMO) does not apply to this study and therefore an official approval of this study by the MREC Utrecht was not required under the WMO (reference number WAG/avd/20/010579). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The data underlying this article cannot be shared publicly for the privacy of individuals that participated in the study. The data will be shared on reasonable request to the corresponding author.