Cardiac injury and mortality in patients with Coronavirus disease 2019 (COVID-19): insights from a mediation analysis

Alberto Cipriani,Leonardo Molinari,Alois Saller,Roberto Vettor,Davide Ceccato,Lorenzo Previato,Sabino Iliceto,Cristiano Sarais,Paola Fioretto,Federico Capone,Filippo Donato,Raffaele Pesavento,Dario Gregori,Angelo Avogaro

doi:10.1007/s11739-020-02495-w

Alberto Cipriani, Leonardo Molinari + Show 12 more

Open Access

https://doi.org/10.1007/s11739-020-02495-w

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Abstract

BackgroundsPatients at greatest risk of severe clinical conditions from coronavirus disease 2019 (COVID-19) and death are elderly and comorbid patients. Increased levels of cardiac troponins identify patients with poor outcome. The present study aimed to describe the clinical characteristics and outcomes of a cohort of Italian inpatients, admitted to a medical COVID-19 Unit, and to investigate the relative role of cardiac injury on in-hospital mortality.Methods and resultsWe analyzed all consecutive patients with laboratory-confirmed COVID-19 referred to our dedicated medical Unit between February 26th and March 31st 2020. Patients’ clinical data including comorbidities, laboratory values, and outcomes were collected. Predictors of in-hospital mortality were investigated. A mediation analysis was performed to identify the potential mediators in the relationship between cardiac injury and mortality. A total of 109 COVID-19 inpatients (female 36%, median age 71 years) were included. During in-hospital stay, 20 patients (18%) died and, compared with survivors, these patients were older, had more comorbidities defined by Charlson comorbidity index ≥ 3(65% vs 24%, p = 0.001), and higher levels of high-sensitivity cardiac troponin I (Hs-cTnI), both at first evaluation and peak levels. A dose–response curve between Hs-cTnI and in-hospital mortality risk up to 200 ng/L was detected. Hs-cTnI, chronic kidney disease, and chronic coronary artery disease mediated most of the risk of in-hospital death, with Hs-cTnI mediating 25% of such effect. Smaller effects were observed for age, lactic dehydrogenase, and d-dimer.ConclusionsIn this cohort of elderly and comorbid COVID-19 patients, elevated Hs-cTnI levels were the most important and independent mediators of in-hospital mortality.

Highlights

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection shows fast contagiousness and a high rate of morbidity and mortality [1,2,3,4]
Cardiac injury, demonstrated by the rise of high-sensitivity cardiac troponins is a common finding in patients with severe COVID-19 and previous reports pointed it as a strong predictor of adverse outcome [9,10,11,12]
The link between cardiac injury and mortality is unclear: it is not known whether there is a direct effect of cardiac injury on mortality or whether this effect is mediated by the underlying comorbid conditions

Summary

Introduction

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection shows fast contagiousness and a high rate of morbidity and mortality [1,2,3,4]. Assessing the severity of coronavirus disease 2019 (COVID-19) is crucial for a correct triage and prioritization. Cardiac injury, demonstrated by the rise of high-sensitivity cardiac troponins is a common finding in patients with severe COVID-19 and previous reports pointed it as a strong predictor of adverse outcome [9,10,11,12]. Such observations may justify considering other pathogenetic mechanisms of myocardial damage, beyond the direct viral infection of the myocardium by SARS-CoV-2. Little is known about the clinical significance of cardiac injury in non-critically ill COVID-19 patients. The link between cardiac injury and mortality is unclear: it is not known whether there is a direct effect of cardiac injury on mortality or whether this effect is mediated by the underlying comorbid conditions

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