key: cord-0934882-dnp4u0rz
authors: Parwani, Abdul Shokor; Haug, Marcel; Keller, Theresa; Guthof, Tim; Blaschke, Florian; Tscholl, Verena; Biewener, Sebastian; Kamieniarz, Paul; Zickler, Daniel; Kruse, Jan; Angermair, Stefan; Treskatsch, Sascha; Müller-Redetzky, Holger; Pieske, Burkert; Stangl, Karl; Landmesser, Ulf; Boldt, Leif-Hendrik; Huemer, Martin; Attanasio, Philipp
title: Cardiac arrhythmias in patients with COVID-19: Lessons from 2300 telemetric monitoring days on the intensive care unit
date: 2021-04-16
journal: J Electrocardiol
DOI: 10.1016/j.jelectrocard.2021.04.001
sha: 646e0ce6b526931f49e49cff0aa48c351ef9cfc5
doc_id: 934882
cord_uid: dnp4u0rz

BACKGROUND: Patients with COVID-19 seem to be prone to the development of arrhythmias. The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment. METHODS AND RESULTS: A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days. Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented. Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%). Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease. The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients. All episodes could be terminated by immediate defibrillation/cardioversion. Five bradycardic events were associated with hemodynamic deterioration. Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing. Baseline characteristics were not significantly different between patients with or without bradycardic events. CONCLUSION: Relevant arrhythmias are common in severely ill ICU patients with COVID-19. They are associated with worse courses of disease and require specific treatment. This makes daily close monitoring of telemetric data mandatory in this patient group.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus first detected in Wuhan, China, that causes coronavirus disease 2019 . The SARS-CoV-2 outbreak has rapidly spread and developed to a pandemic, leading to significant morbidity and mortality. Cardiac injury is a common condition among hospitalized patients with COVID-19 and is associated with a higher risk of fatal outcome of COVID-19 [1, 2] .

Emerging data also indicate that the incidence of cardiac arrhythmias is increased in patients with COVID-19 infection and a considerable number of patients with worse outcome presented with cardiovascular comorbidities (up to 15%) [3] . Guan et al. reported nonspecific heart palpitations in 7.3% of patients admitted due to COVID-19 [3] . Among patients hospitalized with COVID-19 the reported incidence of cardiac arrhythmias ranged between 15-40% [1, 4, 5] . Guo et al. showed that patients with COVID-19 and elevated troponin T levels had an increased risk for malignant ventricular tachycardia with an incidence of 11.5%

[1]. Suspected sudden cardiac death was also reported in Italian patients quarantined with mild COVID-19 [6] . In addition, clinical reports indicate that critically ill COVID-19 patients develop sepsis and acute respiratory distress syndrome (ARDS), which is paralleled by a surge of cytokines and might represent the culprit for cardiac injury and consecutive atrial and/or ventricular arrhythmias in these patients [7] . This data suggest that cardiac arrhythmias in patients with COVID-19 significantly contribute to morbidity and mortality and are relevant for the disease pathophysiology. However, specifics about the types of arrhythmias that occur in COVID-19 patients are lacking. The aim of this study was to describe the incidence and type of cardiac arrhythmias and to identify potential associations with comorbidities as well as severity and course of COVID-19.

In this prospective, observational trial, adult patients admitted to an ICU at one of the three sites of the university hospital center at the Charité Berlin from March to May 2020 were included in the analysis. Patients were only included if ICU treatment was primarily due to respiratory deterioration of COVID-19. All patients had positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement. The end of the observation period was 14 days after the last included patient.

On admission, as part of a routine, patient demographics and medical history including history of cardiac arrhythmias and long-term medications, were recorded. Specific data including oxygenation index, vasopressor support, antibiotic therapy, ventilation mode, need for transfusion and validated mortality prediction scores including Acute Physiology and Chronic Health Evaluation II (APACHE II), Sepsis-related Organ Failure Assessment (SOFA) and Simplified Acute Physiology Score (SAPS-2) were documented. The laboratory values on admission were considered as baseline. To account for disease progression and dynamics, the maximal or minimal values of laboratory parameters and mortality prediction scores corresponding to a worsening of the clinical condition during the course of the ICU stay were noted at the end of the study period.

Continuous telemetric 3-lead electrocardiogram (ECG) data was available for all patients.

Interpretation was conducted by 4 experienced electrophysiologists blinded for patient name and history. Standard 12-lead ECGs were recorded when deemed necessary to differentiate or confirm arrhythmias. Atrial fibrillation (AF) was defined according to ESC guidelines with a minimum duration of more than 30 seconds [ 8 ] . New onset sustained atrial tachycardias (AT)/AF episodes were defined as tachycardias that were not present at the time of ICU admission. The cut-off for a significant number of premature ventricular beats (PVC) was set to more than 30 per hour, as more than 30 PVCs may be associated with worse outcomes in ICU [ 9 ] . Non-sustained ventricular tachycardia (VT) was defined as three or more consecutive ventricular beats (>100 beats/min), lasting longer than 30 seconds [ 10 ] .

J o u r n a l P r e -p r o o f Arrhythmias were defined as hemodynamically relevant if they lead to a systolic blood pressure reduction below a mean arterial pressure of 65 mmHg, if vasopressors had to be initiated or increased or if a cardioversion was carried out immediately.

All arrhythmias occurring in a one-hour time window before any death not directly related to a malignant arrhythmia were excluded. This study was approved by the institutional ethical committee.

Descriptive methods were used for analysis of all clinical and demographic parameters. For continuous variables, the arithmetic average ± standard deviation or median with 25% and 75% percentile were calculated, for categorical values absolute and relative frequencies are indicated. To analyze potential associations between clinical parameters such as scores indicating severity of illness and arrhythmia events we used Mann-Whitney U tests in case of skewed data, independent sample t-tests was used for normally distributed variables and chisquared tests for categorical variables. As this study is explorative, no adjusting for multiple testing was performed. All analyses were explorative, p-values are interpreted as such.

Statistical analysis was performed with SPSS version 25 (IBM, Armonk, USA).

A total of 113 patients (mean age 64.1 ± 14. showed atrial fibrillation (AF) with slow conduction to the ventricle (defined as heart rate < 40 bmp) and in 10 patients (8.9%), a second-degree or third-degree AV block was detected (table 2) . Noteworthy, the predominant subtype of AV conduction disorders was a thirddegree AV block (8 out of 10 patients). With the exception of one patient, the AV block was intermittent and lasted only for a few seconds with a narrow complex escape rhythm. In one case, a patient with a third-degree AV block presented with an asystole lasting 30 seconds.

After cardiopulmonary resuscitation (CPR) and medical therapy with atropine and epinephrine, a stable sinus rhythm was established. Interestingly, all patients with a seconddegree or third-degree AV block showed evidence of myocardial injury, defined as elevated J o u r n a l P r e -p r o o f high-sensitivity Troponin (hs-TnT) levels above the 99th percentile (>16 ng/l). However, it must be said that cardiac arrhythmias can also cause biomarker elevation [ 11, 12 ].

In addition, the reservation must be made that hs-TnT levels were not determined in one patient with a second-degree AV block and in one patient with a third-degree AV block.

In our study population, 93% of the patients with atrial or ventricular arrhythmias had elevated hs-TnT levels (> 16 ng/l) compared to 58% of the patients without arrhythmias (p < 0.01). 4 ).

One ischemic stroke potentially associated with the new onset AF was observed. In comparison with previous studies investigating AF incidence in critically ill patients, the incidence in our study population was higher when compared to ARDS patients (10%) [ 11 ] or patients with severe sepsis (weighted incidence 10% (4 to 23%)) and similar compared to patients with septic shock (weighted incidence 23% (6 to 46%)) [ 14, 15 ]. Up to now, two studies infection. In case of hemodynamic instability due to an atrial arrhythmia, an electrical cardioversion was performed. In hemodynamically stable patients, atrial arrhythmias were treated with antiarrhythmic drugs to slow the ventricular rate.

New-onset AF has been associated with higher short-and long-term mortality in patients with sepsis and ARDS hospitalized on ICUs [ 14 ] . We found that new onset atrial arrhythmias were associated with a more severe course of disease, higher levels of biomarkers indicating cardiac involvement, a higher likelihood for the requirement of mechanical ventilation or the use of catecholamines, the development of higher SOFA, APACHE II and SAPS scores and a longer total time on the ICU. Not surprisingly both trials found an association of ventricular arrhythmias with the disease severity, the amount of myocardial injury and underlying cardiovascular disease. Bradycardic episodes associated with hemodynamic deterioration were found in 5 of 113 patients (4.4%), which is similar to the 6.3% reported by Bhatla et al. [ 18 ] .

There are several situations that may cause transient bradycardia or even asystole in critically ill COVID-19 patients. These include increased vagal tone during intubation, trachea suction or patient turning for prone ventilation as well as hypoxemia [ 14 ] . In our study population, we found a correlation of bradycardia events with the above-mentioned conditions in 23% of the cases.

A variety of drugs commonly administered in critically ill patients represent another common cause for Sinus node dysfunction (SND) or AV-Block. These include non-dihydropyridine Cachannel or beta-blockers, digoxinacetylcholinesterase inhibitors, antiarrhythmic drugs, and sympatholytic or parasympathomimetic agents. A dose change or new administration of such an agent was found in 12 of 30 the observed bradycardic events (40%).

Comparison of the characteristics of patients with or without bradycardic episodes revealed no significant differences regarding comorbidities, age or course of disease. This makes a direct link between cardiac involvement of COVID-19 (direct or indirect) and the onset of bradycardic episode unlikely.

Relevant arrhythmias are common in severely ill ICU patients with COVID-19. The most common arrhythmias are sustained atrial arrhythmias, which are also associated with worse courses of disease. Sustained ventricular arrhythmias occurred less frequently and only in specific triggering situations. Most bradycardic events observed could be related to vagal

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