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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 1  |  Page : 4-8

Cardiac pauses in critically ill Coronavirus Disease-2019 patients


1 Department of Medicine, Center for Cardiovascular Diseases and Sciences, Louisiana State University Health Sciences Center, Shreveport, LA, USA
2 Department of Internal Medicine, Louisiana State University Health Sciences Center, Shreveport, LA, USA

Date of Submission10-Sep-2020
Date of Acceptance08-Feb-2021
Date of Web Publication27-Mar-2021

Correspondence Address:
Dr. Paari Dominic
LSU Health Science Center, 1501 Kings Highway, Shreveport, LA 71103
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/hm.hm_35_20

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  Abstract 

Importance: Coronavirus disease 2019 is associated with a variety of arrhythmias. However, there are limited data regarding bradyarrhythmias and cardiac pauses in COVID-19. Objective: The objective was to characterize significant cardiac pauses in critically ill COVID-19 patients. Design: This was a case series of 26 consecutive patients with confirmed COVID-19 at an academic medical center in Shreveport, Louisiana. Setting: The study was conducted in the intensive care unit (ICU) and step-down ICU. Participants: Patients were either on mechanical ventilation or high-flow oxygen by nasal cannula. Main Outcomes and Measures: Demographic, clinical, laboratory, and medication data were analyzed. Continuous telemetry monitoring was utilized to record number, type, and duration of bradyarrhythmic events as well as their risk determinants. Results: The median age of the 26 patients was 49.5 years (range 33–78). Fifteen (57.7%) were men. Incidence of significant bradycardia and cardiac pauses, defined as an event, occurred in 11 (42.3%) patients. The median age of patients with an event was 57 years (range 33–66) and 5 (45.5%) were men. The average pause duration was 6.77 s with a range of 1.6–30 s. Five of 11 (45.5%) patients had high-grade atrioventricular (AV) nodal block. One patient required temporary pacemaker insertion for complete heart block and recurrent asystole arrests. A trend toward higher troponin I level in bradyarrhythmia patients was noted (mean troponin I was 2.72 ng/mL, [standard deviation] 4.48) compared to patients without event(s) (mean 0.42 ng/mL 0.52, P = 0.07). Conclusions and Relevance: Significant bradycardic events in critically ill patients with COVID-19 occurred in 42.3% of patients. This is the first case series of such events in COVID-19 patients. Increased awareness of these findings could affect management techniques and call for enhanced monitoring of such patients.

Keywords: Acute COVID-19 cardiovascular syndrome, bradyarrhythmias, cardiac pauses, COVID-19


How to cite this article:
Awwab H, Solorzano JI, Jaisingh KC, Singireddy S, Bailey S, Dominic P. Cardiac pauses in critically ill Coronavirus Disease-2019 patients. Heart Mind 2021;5:4-8

How to cite this URL:
Awwab H, Solorzano JI, Jaisingh KC, Singireddy S, Bailey S, Dominic P. Cardiac pauses in critically ill Coronavirus Disease-2019 patients. Heart Mind [serial online] 2021 [cited 2022 Jul 1];5:4-8. Available from: http://www.heartmindjournal.org/text.asp?2021/5/1/4/312308


  Introduction Top


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus known to cause coronavirus disease 2019 (COVID-19), has affected more than 65 million globally and counting. Studies from around the world have reported cardiac dysrhythmias in patients infected with COVID-19. Some of the first studies that reported cardiac dysrhythmias during the COVID-19 pandemic include: a case series from New York with 393 patients showed that 7.4% of patients had arrhythmias during their hospital stay. Specifically, patients who received invasive mechanical ventilation were more likely to have atrial tachyarrhythmias (17.7%).[1] A study from Italy found a statistically significant rise in out-of-hospital cardiac arrests in 2020 when compared to the same period in 2019.[2] Another case series with 187 COVID-19 patients from China, found that 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias. Elevated troponin levels were associated with more frequent ventricular tachycardia and ventricular fibrillation.[3] Recent studies that are specific to bradyarrhythmias in COVID-19 patients include one case series from New Delhi, India, which reported bradyarrhythmias in seven patients with COVID-19. Five of these patients had complete heart block requiring intervention and two presented with sinus node dysfunction.[4] There have only been few isolated reports on data regarding significant cardiac pauses in critically ill COVID-19 patients.


  Methods Top


Study design and participants

This case series included 26 consecutive patients admitted with COVID-19 infection to the Intensive Care Unit (ICU) or step-down ICU at Ochsner-Louisiana State University (LSU) Hospital in Shreveport, Louisiana, from April 29 to May 15, 2020, and was approved by the Institutional Review Board (ID: STUDY00001490). All patients had confirmed COVID-19 infection using real-time reverse transcription-polymerase chain reaction procedure performed at the Emerging Viral Threat Laboratory at LSU Health Sciences Center in Shreveport.

Data collection

Demographic, clinical, laboratory, medications, electrocardiogram (EKG), and echocardiogram findings were collected through electronic medical records. Continuous telemetry recordings were analyzed for cardiac arrhythmias. The following information surrounding arrhythmic events was analyzed: (1) Oxygen saturation (2) Any obvious triggers for dysrhythmia such as airway suctioning, medications, or electrolyte derangements (3) The number, duration, and type of cardiac pauses (4) The type of respiratory support (5) The use of hydroxychloroquine, azithromycin, and anticoagulation (6) Laboratory data (7) Baseline QRS duration, PR interval, and QRS interval on EKG. A significant bradyarrhythmic event was defined as a sudden drop in heart rate (50% or more) within 5 beats resulting in an R-R interval of 1.6 s (s) (rate <37.5 bpm) with or without an escape rhythm. Changes in medication were made if necessary and observation of telemetry for cardiac events was continued. Information regarding the withdrawal of care and subsequent departure of patients was documented.

Statistical analysis

Baseline characteristics of patients with and without bradyarrhythmias and the features of the bradyarrhythmias were summarized. Categorical variables were summarized as rates and continuous variables as mean standard deviation (SD). Continuous variables were compared between patients with and without bradyarrhythmias using a student t-test and categorical variables were compared using a Fisher exact test.


  Results Top


Twenty-six patients with confirmed COVID-19 were included in the study (median age 49.5 years [range 33–78 years]; 15/26 [57.7%] were men) and were followed for 10.27 ± 5.13 days in the ICU or step-down ICU setting. Significant bradyarrhythmic events occurred in 11 (42.3%) patients (median age 57 years [range 33–66 years], 5/11 [45%] were men). The predominant presenting symptoms and underlying comorbidities are listed in [Table 1]. Hypertension was the most common underlying comorbidity among all patients (17/26, 65.4%) [Table 1].
Table 1: Comparison of event-positive and event-negative patients

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The average pause duration of the longest pause was 6.77 s with a range of 1.6 s to 30 s (examples of pauses shown in [Figure 1]a, [Figure 1]b, [Figure 1]c). Among bradyarrhythmia patients, 5/11 (45.5%) had high-grade AV nodal block and/or complete heart block and the rest (54.5%) had sino-atrial node pause (<2 s) or arrest (>2 s). 4/11 (35.4%) patients had one or more junctional escape beats, 3/11 (27.3%) patients had one or more ventricular escape beats. The number of pauses per patient ranged from 1 to 8 during the observed period. Among patients with cardiac pauses, seven (63.6%) were on Dexmedetomidine at the time of the event. Dexmedetomidine was discontinued in six patients and pauses recurred despite discontinuation in three patients [Table 2].
Figure 1: Significant pause events in patients #1, 4, and 2 (a-c, respectively). The arrows in a and c show nonconducted P waves due to atrioventricular nodal block. Tracing b shows a pause due to sinus arrest. Tracing c is a recording in a patient 3 days after dexmedetomidine was stopped

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Table 2: Details of bradyarrhythmic events in critically ill COVID-19 patients

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A statistical trend toward higher troponin-I level was observed in bradyarrhythmia patients (mean [SD], 2.72 ng/mL [4.48] vs. 0.42 ng/mL [0.52], P = 0.07) (to convert nanograms per milliliter to micrograms per liter, multiply by 1.0). All the patients with and without bradyarrhythmia with a D-dimer measurement had elevated D-dimer (mean [SD], 4128.91 ng/mL (1609.63) and 3996.36 ng/mL (1756.95) in event-positive and event-negative patients respectively, P = 0.85). All other biomarkers including NT-proBNP, CRP, and procalcitonin were higher in patients with bradyarrhythmia compared to patients without bradyarrhythmia but were not of statistical significance [Table 1].

Hydroxychloroquine and azithromycin use was comparable in patients with and without bradyarrhythmias [Table 1]. 4/11 (36%) bradyarrhythmia patients had a prolonged QTc interval compared to 9/13 (69%) event-negative patients (P = 0.2). Although, 4/11 (36%) bradyarrhythmia patients had a prolonged QTc interval compared to 9/13 (69%) event-negative patients (P = 0.2), the average QTc intervals were similar between patients with and without bradyarrhythmia (event-positive 458 ms (59.6), event-negative 462.69 ms (36.12)). The average PR interval and QRS duration were also similar between patients with and without bradyarrhythmia. There were more patients without bradyarrhythmia on dexmedetomidine compared to bradyarrhythmia patients, but this difference was not statistically significant (87% of event-negative were on dexmedetomidine vs. 64% event-positive, P = 0.35).

Of the 11 patients with cardiac pauses, one patient had recurrent asystole arrests and complete heart block despite stopping dexmedetomidine. He underwent placement of a temporary transvenous pacemaker [[Figure 1]a and [Table 2], patient #1]. This patient used the temporary device intermittently for the first 72 h but later did not need temporary pacing, so the pacing wire was removed. One patient had an initial pause episode when her potassium was within normal limits but 2 days later had a second episode that was determined to be due to severe hyperkalemia. She underwent cardiopulmonary resuscitation and unfortunately did not survive [[Table 2], patient #8].


  Discussion Top


COVID-19 can affect the heart in various ways including myocarditis, acute coronary syndrome, and depressed left ventricular systolic function, collectively termed acute COVID-19 cardiovascular syndrome.[5] However, its effect on the heart rhythm is unclear. Although cardiac arrhythmias and increased cardiac arrests have been previously reported, this is the first report of cardiac pauses in critically ill patients with COVID-19.

Out of 26 patients that were observed in the ICU and step-down ICU with confirmed COVID-19, 42% were found to have significant bradyarrhythmic events [Table 2]. Dexmedetomidine, an α-2 adrenergic receptor agonist used as a sedative and analgesic, has been known to cause baroreflex-mediated reduction in heart rate, causing severe bradycardia.[6] However, sinus arrest or AV block causing cardiac pauses or asystole with dexmedetomidine is rather uncommon. In our case series, 64% of bradyarrhythmia patients were on dexmedetomidine compared to 87% (P = 0.35) of the event-negative patients [Table 1]. When analyzed based on the use of dexmedetomidine, patients on dexmedetomidine were not more or less likely to develop pauses. Furthermore, azithromycin and hydroxychloroquine that are associated with QT prolongation did not show a significant association with bradyarrhythmias. Some of the medications that have been used to treat COVID-19 have been associated with significant bradyarrhythmias. One study from France which included 41 critically ill COVID-19 patients who received treatment with lopinavir-ritonavir, evidenced significant bradycardia in 22% of the patients. These episodes of bradycardia resolved after discontinuation or dose reduction of these drugs.[7] In our study, none of the patients were on lopinavir-ritonavir treatment.

The cardiac pauses observed in our patients is likely multifactorial and could be associated with medications, however we did not find any significant correlation between medications and bradycardic events in our study. The finding of significant sinus slowing, even in patients with AV nodal block suggests extrinsic stimuli as opposed to an intrinsic conduction system disorder as the cause of the events in our COVID-19 patients. COVID-19 has been reported to cause neurologic manifestations;[8] however, its specific involvement on the autonomic nervous system has not been reported. Furthermore, patients with severe sepsis/acute respiratory distress syndrome typically have decreased heart rate variability, leading to studies exploring vagal stimulation as a therapeutic option. In our patients, we did observe a decrease in heart rate variations [Supplementary content eFigure 1], suggesting a decreased vagal tone except when the events occurred. Vagovagal reflex has been studied as an important anti-inflammatory response.[9],[10] Whether these pauses are a direct effect of an increased vagal tone in response to the body's attempts to deal with the inflammation is not clear. At the least, this observed phenomenon of pauses appears to be multifactorial and may be due to a combination of COVID-19 neurological manifestations, and an intense vagovagal reflex due to the ongoing systemic inflammation. There are limitations to the study. This is a small, single-center study lacking the power to detect associations or lack thereof between events and biomarkers. Due to the lack of uniformity in arterial line placements for invasive continuous blood pressure monitoring in all the patients, a concurrent hemodynamic correlation to the rhythm abnormalities, unfortunately, could not be made.


  Conclusion Top


Although our case series involves a small sample size, the findings of bradyarrhythmic events observed in our study should raise awareness of an increased risk of cardiac pauses in COVID-19. Enhanced monitoring could influence the future management of patients infected with SARS-CoV-2 and larger scale studies might yield new findings.

Financial support and sponsorship

Finally, this study was supported in part by P20GM121307 from the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Center for Redox Biology and Cardiovascular Diseases at the Center of Excellence for Cardiovascular Disease, LSU Health Science Center at Shreveport.

Conflicts of interest

Prof. Steven Bailey is the Associate Editor-in-Chief of the Heart and Mind journal.



Supplementary Online Content

This supplementary online content is to provide readers with additional information about our work.

Legend: eFigure 1. Visual trend of patient number 7(A) and patient number 6(B), showing decreased heart rate variations other than during pause events



All representative patient events summarized below:







Patient Number 2















Patient Number 3





Patient Number 4









Patient Number 5







Patient Number 6







Patient Number 7





Patient Number 8





Patient Number 9



Patient Number 10





Patient Number 11







 
  References Top

1.
Goyal P, Choi JJ, Pinheiro LC, Schenck EJ, Chen R, Jabri A, et al. Clinical characteristics of Covid-19 in New York City. N Engl J Med 2020;382:2372-4.  Back to cited text no. 1
    
2.
Baldi E, Sechi GM, Mare C, Canevari F, Brancaglione A, Primi R, et al. Out-of-hospital cardiac arrest during the Covid-19 outbreak in Italy. N Engl J Med 2020;383:496-8.  Back to cited text no. 2
    
3.
Guo T, Fan Y, Chen M, Wu X, Zhang L, He T, et al. Cardiovascular implications of fatal outcomes of patients with coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020;5:811-8.  Back to cited text no. 3
    
4.
Gupta MD, Qamar A, Mp G, Safal S, Batra V, Basia D, et al. Bradyarrhythmias in patients with COVID-19: A case series. Indian Pacing Electrophysiol J 2020;20:211-2.  Back to cited text no. 4
    
5.
Hendren NS, Drazner MH, Bozkurt B, Cooper LT Jr. Description and Proposed Management of the Acute COVID-19 Cardiovascular Syndrome. Circulation 2020;141:1903-14.  Back to cited text no. 5
    
6.
Talke P, Chen R, Thomas B, Aggarwall A, Gottlieb A, Thorborg P, et al. The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery. Anesth Analg 2000;90:834-9.  Back to cited text no. 6
    
7.
Beyls C, Martin N, Hermida A, Abou-Arab O, Mahjoub Y. Lopinavir-ritonavir treatment for COVID-19 infection in intensive care unit: Risk of bradycardia. Circ Arrhythm Electrophysiol 2020;13:e008798.  Back to cited text no. 7
    
8.
Mao L, Jin H, Wang M, Hu Y, Chen S, He Q, et al. Neurologic manifestations of hospitalized patients with coronavirus disease 2019 in Wuhan, China. JAMA Neurol 2020;77:683-90.  Back to cited text no. 8
    
9.
Boeckxstaens G. The clinical importance of the anti-inflammatory vagovagal reflex. Handb Clin Neurol 2013;117:119-34.  Back to cited text no. 9
    
10.
Tanaka S, Hammond B, Rosin DL, Okusa MD. Neuroimmunomodulation of tissue injury and disease: An expanding view of the inflammatory reflex pathway. Bioelectron Med 2019;5:13.  Back to cited text no. 10
    


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