key: cord-1045068-iaiyd6gf authors: Russo, Vincenzo; Di Maio, Marco; Mottola, Filiberto; Pagnano, Gianpiero; Attena, Emilio; Verde, Nicoletta; Di Micco, Pierpaolo; Silverio, Angelo; Scudiero, Fernando; Nunziata, Luigi; Fele, Nunzia; D’Andrea, Antonello; Parodi, Guido; Albani, Stefano; Scacciatella, Paolo; Nigro, Gerardo; Severino, Sergio title: Clinical characteristics and prognosis of hospitalized COVID‐19 patients with incident sustained tachyarrhythmias: a multicenter observational study date: 2020-08-19 journal: Eur J Clin Invest DOI: 10.1111/eci.13387 sha: e0c2b34ceaa78fac31085a335d6763588bed0f79 doc_id: 1045068 cord_uid: iaiyd6gf INTRODUCTION: Little is still known about the prognostic impact of incident arrhythmias in hospitalized patients with COVID‐19. Aim of our study is to evaluate the incidence and predictors of sustained tachyarrhythmias in hospitalized patients with COVID‐19, and their potential association with disease severity and in‐hospital mortality. MATERIALS AND METHODS: This was a retrospective multicenter observation study including consecutive patients with laboratory confirmed COVID‐19 admitted to emergency department of ten Italian Hospitals from February 15(th) to March 15(th) 2020. The prevalence and the type of incident sustained arrhythmias have been collected. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in‐hospital mortality has been evaluated. RESULTS: 414 hospitalized patients with COVID‐19 (66.9 ± 15.0 years, 61.1% male) were included in the present study. During a median follow‐up of 28 days (IQR: 12‐ 45), the most frequent incident sustained arrhythmia was AF (N: 71; 17.1%), of which 50 (12.1%) were new‐onset and 21 (5.1%) were recurrent, followed by VT (N: 14, 3.4%) and supraventricular arrhythmias (N: 5, 1.2%). Incident AF, both new‐onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast incident VT significantly increased the risk of in‐hospital mortality (RR: 2.55; P:0.003). CONCLUSIONS: AF is the more frequent incident tachyarrhythmia; however, it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in‐hospital mortality among hospitalized COVID‐19 patients. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic human coronavirus recently recognized as the cause of the coronavirus disease 2019 (COVID-19). The outbreak sparked in China and spread rapidly to other countries, reaching devastating pandemic proportion (1) . Italy is the one of the hardest hit countries by COVID-19, with more than 236,000 laboratory-confirmed cases by Jun 14, 2020 (2) . The clinical course of COVID-19 may be frequently complicated by cardiac arrhythmias, both atrial and ventricular (3) . Actually, little is still known about the clinical characteristics of COVID-19 patients who developed arrhythmias during hospitalization (4); the type and burden of incident sustained tachyarrhythmias; the clinical impact of atrial fibrillation (AF) or ventricular tachycardia (VT) on disease severity and inhospital mortality. The aim of this multicenter study was to evaluate the incidence and the predictors of sustained tachyarrhythmias in hospitalized patients with COVID-19, and their potential association with disease severity and in-hospital mortality. All consecutive patients with laboratory confirmed COVID-19 admitted to emergency department of ten Italian Hospitals from February 15 th to March 15 th were included in this retrospective observational study All patients underwent medical history, physical examination, electrocardiographic and laboratory evaluation. Chest X-Ray and/or Computed Tomography (CT) scan were also performed to rule out pneumonia in one or multiple sites. The primary aim of our study was to explore the incidence and predictors of most common incident tachyarrhythmias (i.e. atrial fibrillation and ventricular tachycardias) in hospitalized COVID-19 patients. The secondary aim was to verify if atrial fibrillation and/or ventricular tachycardias were independently associated with ARDS and/or in-hospital mortality. The correlation between the most prevalent arrhythmias and both baseline characteristics and the development of ARDS and in-hospital mortality has been evaluated. ARDS diagnosis was defined according to the Berlin definition (5). This article is protected by copyright. All rights reserved Distribution of continuous data was tested with the Kolmogorov-Smirnov and the Shapiro-Wilk test. Normally distributed variables were expressed as mean ± standard deviation (SD), whereas non-normal distributed ones as median and interquartile range (IQR). Categorical variables were reported as numbers and percentages. The unadjusted (univariable) and adjusted (multivariable) risk ratios (RR) both for incident tachyarrhythmias and the outcomes of interest were calculated using logistic regression models and presented as RR with their 95% confidence intervals (CI). All independent variables showing a p value <0.1 for the association with the response variable at univariable analysis were tested in the multivariable model. For all tests, a p value <0.05 was considered statistically significant. Analyses were performed by using R version 3.5.1 (R Foundation for Statistical Computing, Vienna, Austria). 414 hospitalized patients with COVID-19 were included in the present study. The mean age was 66.9 ± 15.0 years; 253 (61.1%) were males. The median follow-up was 28 days (IQR: 12-45). Incident tachyarrhythmias were reported in 90 cases (21.7%). The most frequent incident This article is protected by copyright. All rights reserved The main findings of the present study can be summarized as follows: the incident sustained tachyarrhythmias occur in 21% of our study population including COVID-19 hospitalized patients. AF was the most prevalent arrhythmia accounting for the 18.45% of cases and its independent predictors were older age, male gender, HF and CAD; moreover, incident AF was a significantly associated with incident VT. VT occurred in a small percentage of COVID-19 patients (3.4%) and was independently associated with recurrent AF. Incident AF, both new-onset and recurrent, did not affect the risk of severe adverse events including ARDS and death during hospitalization; in contrast incident sustained VT significantly increased the risk of in-hospital mortality. There are few and conflicting data about the occurrence of arrhythmias in the context of COVID-19, however the clinical presentation seems not different from that described in general population (6) . In the cohort study by Wang et al. In the present analysis, the incident AF, both new-onset and recurrent, did not influence the clinical outcome of patients with COVID-19 in terms of ARDS developing and survival, differently from what happens in critically ill patients with sepsis among general population (15). In contrast, the incident VT seems to be a strong independent predictor of in-hospital mortality among COVID-19 patients; to date VT has not ever been described as mortality predictor in the clinical contest of sepsis or viral infection (16, 17). Based on our results, tachyarrhythmias, in particular AF, could complicate the clinical course of COVID-19 during hospitalization and in case of VT could worsen the prognosis of infected patients. Thereafter, a careful electrocardiographic monitoring would be advisable in COVID-19 patients to early detect incident tachyarrhythmias that, even though not matching the apparent disease status, might be a red flag of worsening disease. The present study has several limitations: the retrospective nature of the analysis; our limited ability to detect subclinical arrhythmias; the heterogeneity in the characteristics of the different wards where the study patients were hospitalized; the relatively high number of covariates tested in the regression models in relation of the number of patients. Furthermore, some potential confounders could have been not considered in our analysis, that was restricted on available data. Larger multicenter prospective studies are required to confirm our preliminary findings. This article is protected by copyright. All rights reserved CONCLUSION Incident sustained tachyarrhythmias represent a not rare complication of COVID-19. Among them, AF is the more frequent, however it not seems associated to ARDS development and death. On the other hand, incident VT is a not frequent but independent predictor of in-hospital mortality among hospitalized COVID-19 patients. The careful electrocardiographic monitoring would be advisable in COVID-19 patients to optimize the clinical management of the disease. 16 Accepted Article The continuing 2019-nCoV epidemic threat of novel coronaviruses to global health -The latest 2019 novel coronavirus outbreak in Wuhan, China World Health Organization Coronavirus disease (COVID-19) Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area COVID-19 and Heart: From Clinical Features to Pharmacological Implications ARDS Definition Task Force. Acute respiratory distress syndrome: the Berlin Definition Analysis of myocardial injury in patients with COVID-19 and association between concomitant cardiovascular diseases and severity of COVID-19 Accepted Article This article is protected by copyright. All rights reserved Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan COVID-19 and Cardiac Arrhythmias Atrial Arrhythmias in COVID-19 Patients Cardiac involvement in a patient with coronavirus disease 2019 (COVID-19) Arrhythmias in myocarditis: state of the art Severe sepsis and cardiac arrhythmias Impaired regulation of cardiac function in sepsis, SIRS, and MODS COVID-19, arrhythmic risk and inflammation: mind the gap! Circulation 66. 86 This article is protected by copyright. All rights reserved Accepted Article Figure 2 : Forest plot visual summary of the results of logistic regression models.