The value of ECG changes in risk stratification of COVID‐19 patients

Abstract Background There is growing evidence of cardiac injury in COVID‐19. Our purpose was to assess the prognostic value of serial electrocardiograms in COVID‐19 patients. Methods We evaluated 269 consecutive patients admitted to our center with confirmed SARS‐CoV‐2 infection. ECGs available at admission and after 1 week from hospitalization were assessed. We evaluated the correlation between ECGs findings and major adverse events (MAE) as the composite of intra‐hospital all‐cause mortality or need for invasive mechanical ventilation. Abnormal ECGs were defined if primary ST‐T segment alterations, left ventricular hypertrophy, tachy or bradyarrhythmias and any new AV, bundle blocks or significant morphology alterations (e.g., new Q pathological waves) were present. Results Abnormal ECG at admission (106/216) and elevated baseline troponin values were more common in patients who developed MAE (p = .04 and p = .02, respectively). Concerning ECGs recorded after 7 days (159), abnormal findings were reported in 53.5% of patients and they were more frequent in those with MAE (p = .001). Among abnormal ECGs, ischemic alterations and left ventricular hypertrophy were significantly associated with a higher MAE rate. The multivariable analysis showed that the presence of abnormal ECG at 7 days of hospitalization was an independent predictor of MAE (HR 3.2; 95% CI 1.2–8.7; p = .02). Furthermore, patients with abnormal ECG at 7 days more often required transfer to the intensive care unit (p = .01) or renal replacement therapy (p = .04). Conclusions Patients with COVID‐19 should receive ECG at admission but also during their hospital stay. Indeed, electrocardiographic alterations during hospitalization are associated with MAE and infection severity.


| Study subjects and design
Thestudyenrolled269consecutivepatientsadmittedtoSant'Orsola -Malpighi Hospital of Bologna University with laboratory-confirmed SARS-CoV-2infectionandradiologicalfindingssuggestiveofinter-stitialpneumoniafromMarch01,2020toApril10,2020.Patients werefollowedupuntilApril20,2020 was established according to the WHO interim guidance and con-firmedbyRNAdetectionoftheSARS-CoV-2intheclinicallaboratory of Bologna Hospital . Chest radiographs or computedtomography(CT)scanswerealsodoneforallinpatients to assess lung parenchyma involvement. The exclusion criteria were age under 18 years old, lack of ECG at admission, and interstitial pneumoniawithoutmicrobiologicalconfirmationofSARS-CoV-2.
Written informed consent was waived by the designated hospital's ethics committee for patients with emerging infectious diseases.
Electrocardiogram was defined as abnormal for any patient if ischemia alterations, left ventricular hypertrophy, tachy or bradyarrhythmias,andanynewatrioventricular(AV),bundlebranchblocks, or significant morphology alterations (e.g., new Q pathological waves)werepresent.Otherwise,patientspresentingsinusrhythm without previously described alterations were reported as normal.

| ECG alterations and cardiac involvement in COVID-19
AccordingtotherecentliteratureonCOVID-19,severerespiratory distress was independently associated with the need for intensive careandintra-hospitalmortality(Yangetal.,2020).Newperspectives enlightened that SARS-CoV-2 infection is associated with cardiac injury resulting from a direct or indirect effect on cardiovascular system, as described in other coronavirus strains (Inciardi etal.,2020;Shietal.,2020).ECGisausefultoolineverydaypractice to recognize myocardial damage due to the widespread availability.
Interestingly, abnormal changes at 12-lead electrocardiogram did not reflect the population's baseline clinical characteristics but were directly associated with the severity of COVID-19. In fact, there were no differences in clinical history, hemodynamic state, main laboratory parameters, and medical treatments whether patients had  Sellers et al., 2017). Beyond oxygen supply-demand mismatch, another cause could be the direct protein-receptor interaction.
The spike protein of SARS-CoV-2 has a strong binding affinity to angiotensin-converting enzyme 2 (ACE2) receptor, which is also highly expressed in the heart and in the lung parenchyma (Tikellis &Thomas,2012).
Finally, inflammatory mediators may also trigger arrhythmias (e.g., atrial fibrillation and/or ventricular arrhythmias), especially in the

| Study limitations
Ourstudyhassomelimitations.First,thisstudywasconductedin a single medical center with a relatively small number of patients.
Furthermore, in our study, some clinical or laboratory data at baseline and during follow-up are missing due to practical difficulty in managing clinical reports because of a serious infectious problem.
Finally, due to various logistical issues, only 30 echocardiograms wereperformed,andthesedatawerenotanalyzed.Indeed,itcould be useful to perform an echocardiographic evaluation in each patient with suspected myocardial damage. These findings suggest that in patients with COVID-19, it is a good practice to collect a basal ECG and repeat the 12 lead ECG evaluation during the hospitalization stay due to the high burden of information related.

ACK N OWLED G M ENTS
None.

CO N FLI C T O F I NTE R E S T
None.

E TH I C A L A PPROVA L
Written informed consent was waived by the ethics committee of the designated hospital for patients with emerging infectious diseases.

DATA AVA I L A B I L I T Y S TAT E M E N T
The data that support the findings of this study are available from thecorrespondingauthoruponreasonablerequest.