key: cord-346596-uahjsqzh
authors: DOYEN, Denis; DUPLAND, Pierre; MORAND, Lucas; FOURRIER, Etienne; SACCHERI, Clément; BUSCOT, Matthieu; HYVERNAT, Hervé; FERRARI, Emile; BERNARDIN, Gilles; CARIOU, Alain; Jean-Paul, M.I.R.A.; JAMME, Matthieu; DELLAMONICA, Jean; JOZWIAK, Mathieu
title: Characteristics of cardiac injury in critically ill patients with COVID-19
date: 2020-10-28
journal: Chest
DOI: 10.1016/j.chest.2020.10.056
sha: 
doc_id: 346596
cord_uid: uahjsqzh

Background Cardiac injury has been reported in up to 30% of COVID-19 patients. However, cardiac injury was mainly defined by troponin elevation without description of associated structural abnormalities and its time course has never been studied. Research question What are the electrocardiographic and echocardiographic abnormalities as well as their time course in critically ill COVID-19 patients? Study Design and Methods The cardiac function of 43 consecutive COVID-19 patients admitted in two intensive care units (ICU) was prospectively and repeatedly assessed combining electrocardiographic, cardiac biomarkers and transthoracic echocardiographic analyses from ICU admission (D0) to ICU discharge or death or to a maximum follow-up of 14 days. Cardiac injury was defined by troponin elevation and newly diagnosed electrocardiographic and/or echocardiographic abnormalities. Results At D0, 49% of patients had a cardiac injury and 70% of patients experienced cardiac injury within the first 14 days of ICU stay, with a median time of occurrence of 3[0-7] days. The most frequent abnormalities were electrocardiographic and/or echocardiographic signs of left ventricular (LV) abnormalities (87% of patients with cardiac injury), right ventricular (RV) systolic dysfunction (47%), pericardial effusion (43%), new-onset atrial arrhythmias (33%), LV relaxation impairment (33%) and LV systolic dysfunction (13%). Between D0 and D14, the incidence of pericardial effusion and of new-onset atrial arrhythmias increased, the incidence of electrocardiographic and/or echocardiographic signs of LV abnormalities as well as the incidence of LV relaxation impairment remained stable, whereas the incidence of RV and LV systolic dysfunction decreased. Interpretation Cardiac injury is common and early in critically ill COVID-19 patients. Electrocardiographic and/or echocardiographic signs of LV abnormalities were the most frequent abnormalities and patients with cardiac injury experienced more RV than LV systolic dysfunction.

Results: At D0, 49% of patients had a cardiac injury and 70% of patients experienced cardiac 48 injury within the first 14 days of ICU stay, with a median time of occurrence of 3[0-7] days. 49 The most frequent abnormalities were electrocardiographic and/or echocardiographic signs 50 of left ventricular (LV) abnormalities (87% of patients with cardiac injury), right ventricular 51 (RV) systolic dysfunction (47%), pericardial effusion (43%), new-onset atrial arrhythmias 52 (33%), LV relaxation impairment (33%) and LV systolic dysfunction (13%). Between D0 and 53 D14, the incidence of pericardial effusion and of new-onset atrial arrhythmias increased, the 54 incidence of electrocardiographic and/or echocardiographic signs of LV abnormalities as well 55 as the incidence of LV relaxation impairment remained stable, whereas the incidence of RV 56 and LV systolic dysfunction decreased. 57 Interpretation: Cardiac injury is common and early in critically ill COVID-19 patients. 58 Electrocardiographic and/or echocardiographic signs of LV abnormalities were the most 59 frequent abnormalities and patients with cardiac injury experienced more RV than LV 60 systolic dysfunction. In most studies, cardiac injury was defined by troponin elevation, regardless of new 68 abnormalities in electrocardiography or echocardiography. 5, 6 Moreover in studies also 69 considering electrocardiographic and/or echocardiographic abnormalities to define cardiac 70 injury, the latter were not described, limited to assessment of left ventricular (LV) systolic 71 function 2,4,7 or were described in non-critically ill patients. 8 Finally, no study has described 72 the time course of cardiac injury during COVID-19. 73 This study aimed to prospectively characterize cardiac injury and its time course in This prospective and observational study was conducted in two ICUs of university 80 hospitals. This study was approved by our institutional review board (IDRCB number: 2020-81 A01197-32) and all patients or next of kin were informed about the study and consented to 82 participate.

Patients 85 We included all consecutive patients with COVID-19 confirmed by real-time reverse 86 transcriptase-polymerase chain reaction assay of nasal swabs or pulmonary samples. bundle branch block, ventricular arrhythmia and severe brady-arrhythmia)) 9,11-15 and (ii) 114 new-onset atrial arrhythmias (atrial fibrillation, atrial flutter or atrial tachycardia). 115 Newly diagnosed echocardiographic abnormalities defining cardiac injury were the 116 following: (i) echocardiographic signs of LV abnormalities suggestive of coronary heart 117 disease, Takotsubo syndrome, myocarditis or septic cardiomyopathy (mild, moderate or 118 severe LV systolic dysfunction or wall motion abnormalities), 9,11-15 (ii) LV relaxation 119 impairment (i.e. LV diastolic dysfunction), with at least two of the following abnormalities: injury is a competing event with death without cardiac injury or discharge alive from ICU), 148 we plotted cumulative incidence function to illustrate time-to-event analysis. Statistical (Table 1 and Table 2 (Table 3) . 179 Similarly, patients with new-onset atrial arrhythmias required more frequent vasopressor Table 4, Table   192 5, Figure 2 into account to define cardiac injury, 2,4,7 whereas we and others, 8 found that patients with 238 cardiac injury experienced more RV than LV systolic dysfunction. Finally, the higher incidence 239 of cardiac injury that we found could be explained by the potential ascertainment bias of 240 prior cohort studies, related to a non-longitudinal cardiac assessment. Thus, it cannot be 241 excluded that the prevalence we found is more indicative of the true prevalence of cardiac 242 injury in critically ill COVID-19 patients. 243 Patients with COVID-19 appeared to experience as much newly diagnosed cardiac 244 abnormalities as non-COVID-19 critically ill patients, 20 suggesting that these different cardiac 245 abnormalities may not be totally specific to COVID-19, but may also reflect the severity of without, suggesting that vasopressor use may be the trigger for atrial arrhythmias through 300 the activation of beta-receptors. Nevertheless, it cannot be excluded that the need for 301 vasopressors is a consequence of the potential hemodynamic impairment induced by atrial 302 arrhythmias. 303 We acknowledge some limitations to our study. First, we included a relatively small 304 number of patients but no new COVID-19 patients were admitted in our ICUs after May. 305 Nevertheless, this is the first study providing the frequency and a multimodal description of 3 (10) 2 (7) 2 (7) 2 (7) 2 (7) 2 (7) 0 (0) 0 (0) Data are expressed as number (%) or mean±standard deviation. no=number of patients. E=early peak velocity of the mitral flow with pulsed Doppler; A=atrial peak velocity of the mitral flow with pulsed Doppler; e'=early diastolic peak velocity of the lateral and septal mitral annulus with Tissue Doppler Imaging; ECG=electrocardiogram. 

J o u r n a l P r e -p r o o f 

Clinical Characteristics of Coronavirus Disease 2019 in China

Clinical features of patients infected with 2019 novel 339 coronavirus in Wuhan

Association of Cardiac Injury With Mortality in Hospitalized 341 Patients With COVID-19 in Wuhan, China

Characteristics and Outcomes of 21 Critically Ill Patients 343

With COVID-19 in Washington State

Characteristics and clinical significance of myocardial injury in 345 patients with severe coronavirus disease 2019

Acute Myocardial Injury at Hospital Admission Is Associated With 347

All-Cause Mortality in COVID-19

Clinical Characteristics of 138 Hospitalized Patients With

Novel Coronavirus-Infected Pneumonia in Wuhan

The Spectrum of Cardiac Manifestations in Coronavirus 351 Disease 2019 (COVID-19) -a Systematic Echocardiographic Study

Fourth Universal Definition of Myocardial Infarction

Recommendations for cardiac chamber 355 quantification by echocardiography in adults: an update from the American Society of 356

Echocardiography and the European Association of Cardiovascular Imaging

ESC Guidelines for the diagnosis and 359 management of chronic coronary syndromes

The Septic Heart: Current Understanding of 361

Myocarditis in Clinical Practice

Takotsubo Syndrome (Part I): Clinical Characteristics, Diagnostic Criteria, and 366 Pathophysiology

Global evaluation of echocardiography in patients 368 with COVID-19

ESC/EACTS Guidelines for the management of 373 valvular heart disease

Cardiovascular Implications of Fatal Outcomes of Patients 375

COVID-19)

High-Sensitivity Cardiac Troponin Can Be An Ally in the 377 Fight Against COVID-19

Range and prevalence of cardiac abnormalities in 379 patients hospitalized in a medical ICU

Atrial fibrillation in the COVID-19 era: simple 381 bystander or marker of increased risk?

Frequency and prognostic impact of basic critical 383 care echocardiography abnormalities in patients with acute respiratory distress syndrome

Ventricular diastolic abnormalities in the critically ill

Practical approach to diastolic 388 dysfunction in light of the new guidelines and clinical applications in the operating room and 389 in the intensive care

Prognostic Value of Right Ventricular 418 Longitudinal Strain in Patients with COVID-19

Right Ventricular Dilation in Hospitalized Patients with 420 COVID-19 Infection

COVID-19 and Thrombotic or Thromboembolic 422 Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up

Pulmonale in Critically Ill Patients with Covid-19

Clinical spectrum, frequency, and significance of 427 myocardial dysfunction in severe sepsis and septic shock

ESC/ESH Guidelines for the management of 430 arterial hypertension

COVID-19, Arrhythmic Risk and Inflammation: Mind 432 the Gap! Circulation

Cardiac and arrhythmic 434 complications in patients with COVID-19

Atrial Fibrillation in the ICU

ST segment elevation, no. (%) ST segment depression, no. (%) Pathological Q waves, no. (%) Localization of repolarization abnormalities and Q waves Anterior, no. (%) Lateral, no. (%) Inferior, no. (%) Infero-lateral, no. (%) Diffuse, no. (%) New left branch bundle block, no. (%) Life-threatening ventricular arrhythmia, no. (%) Severe bradyarrhythmia, no. (%) New-onset atrial arrhythmias Atrial fibrillation, no. (%) Atrial flutter, no. (%) Atrial tachycardia, no. (%) Signs of right ventricular strain

Hg Tricuspid annular plane systolic excursion (mm) Systolic tricuspid annular velocity (cm/s) Right ventricular fractional area change (%) Right/left ventricular end-diastolic areas ratio ECG abnormalities ECG signs of LV abnormalities, no. (%) Inverted T waves, no. (%) ST segment elevation, no. (%) ST segment depression, no. (%) Pathological Q waves, no. (%) New left branch bundle block, no. (%) Severe bradyarrhythmia, no. (%) New-onset of atrial arrhythmias, no. (%) Signs of right ventricular strain, no. (%) Echocardiographic abnormalities Echocardiographic signs of LV abnormalities, no. (%) LV wall motion abnormalities, no. (%) LV systolic dysfunction, no. (%) Left ventricular relaxation impairment, no. (%) Cor pulmonale, no. (%) Right ventricular dilation or cor pulmonale, no. (%) Right ventricular systolic dysfunction