Impact of COVID-19 Pandemic on Severe Ventricular Arrhythmia and Icd Therapy

doi:10.21203/rs.3.rs-753735/v1

BACKGROUND AND OBJECTIVES: The regular clinical follow-up of the patient with the implantable cardioverter-defibrillator (ICD) device was seriously affected by the COVID-19 outbreak. Due to the high risk of contamination, patients didn’t admit to the clinics for the ICD device control. It has been observed that arrhythmic events increased during the COVID-19 outbreak. In this study, we aimed to investigate the frequency of severe ventricular arrhythmias and ICD device therapy in COVID-19 patients with ICD.

METHODS: In this single center-observational study, we assessed severe ventricular arrhytmias and ICD therapies by analyzing recorded data of 33 patients (24 males, 72.7%) 3 months before and after getting COVID-19 during the COVID-19 pandemic in Van, Turkey, between 15 August 2020 and 15 January 2021.

RESULTS: Before the diagnosis of COVID-19, 6 ventricular tachycardias and 1 ventricular fibrillation were observed. When we analyzed the records after the diagnosis COVID-19, 17 ventricular tachycardia and 3 ventricular fibrillation episodes were observed. Considering the the ICD device therapies, 5 of these severe tachyarrhythmias were terminated by antitachycardia pacing (ATP) and 2 with shock therapy before the diagnosis of COVID-19. After the COVID-19, 14 of them were terminated by ATP and 6 of them ere terminated by shock therapy.

CONCLUSION: The effects of the COVID-19 pandemic, especially on ventricular arrhythmia, have not been reported sufficiently. In our study, it was observed that life-threatening ventricular arrhythmias and the ICD therapies were increased in patients with COVID-19, especially in the first month after the diagnosis COVID-19.

Cardiac & Cardiovascular Systems

Cardiothoracic Surgery

COVID‐19

Ventricular arrhythmia

Implantable cardioverter-defibrillator.

Although COVID-19 (Corona Virus Disease 2019) mainly affects the lungs, extrapulmonary complications such as cardiac complications are also increasing day by day.¹ SARS-CoV2 (severe acute respiratory syndrome-coronavirus-2) infection is associated with many pro-inflammatory mediators that may play a role in the development of cardiac arrhythmia and complications. In a single center study, cardiac injury was observed in 19 percent of the hospitalized patients. Therefore, it is plausible that these patients have an even higher risk of cardiac arrhythmias.

Ventricular arrhythmias mostly occur in settings associated with increased sympathetic tone, including physical activity, illness, and emotional distres.² Lung injury and hypoxemia caused by the SARS-CoV 2 epidemic may cause irregularity in the electrical activity of the myocardium. In addition, SARS-CoV2 can directly damage myocardial cells and the electrical conduction system of the heart. Again, COVID-19 infection can aggravate the underlying cardiovascular disease, and the release of endogenous catecholamine may disrupt the electrical activity of the myocardium due to increased anxiety.

Patients with ICD (implantable cardioverter-defibrillator) device are always at risk of life-threatening ventricular arrhythmia (VA) and sudden death. We analyzed the data of the old ICD patients in order to determine whether the device therapy and ventricular arrhythmia burden has increased after the diagnosis of COVID-19.

This is a single center-observational study. Patients with previously implanted ICD device (CRT-D, VVIR-ICD or DR-ICD) due to systolic left ventricular dysfunction or cardiac arrest and syncope and who were positive for COVID-19 PCR (+) were included in this study. Data obtained from the ICD of 33 patients (24 males) who admitted to the clinic for regular pacemaker control between August 15, 2020 and January 15, 2021 and had positive PCR result for COVID-19 were examined. The 3-month period was examined before and after PCR positivity. Ventricular arrhythmias [ventricular fibrillation (VF) or ventricular tachycardia (VT)] treated by the ICD (ATP or shock) were detected. The development of ventricular tachycardia (VT) and ventricular fibrillation (VF) after COVID-19 was the primary end point of this study

Inclusion criteria

Prior ICD implantation with or without subsequent spontaneous, ventricular tachycardia/ventricular fibrillation (VT/, VF) episodes causing hemodynamic disturbances, or syncope.
COVID-19 PCR+

Patient 18 years of age
And patient on stable optimal pharmacologic therapy for their cardiac condition.

Exclusion criteria

Patients with ICD implanted for Brugada syndrome, long QT syndrome and hypertrophic cardiomyopathy.
Patients treated with catheter ablation for VT.
Patients diagnosed with acute coronary syndrome
and those who received inappropriate ATP or shock therapy were not included in the study.

This study was reviewed and approved by the Ethics Committees of the Van Training and Research Hospital Van, Turkey. Also, all methods were performed in accordance with the relevant cureent guidelines and regulations.

Statistical analysis

All statistical analyzes were done with SAS University Edition (SAS / STAT, SAS Institute Inc, NC, USA). The 45-day period following COVID-19 was compared with each of 45-day periods before and after this period. The number of patients who had an arrhythmic event during the 3 months before and after the COVID-19 infection were compared using McNemar’s test. Mantel-Haenszel statistic was used calculate the relative risk (RR) estimated for the paired data. The number of arrhythmic events were compared using Wilcoxon-signed rank test between paired data. Kaplan-Meier survival curves (time to first event) were reproduced and Gehan’s test for paired data was used for comparision survival curves. 45-day discharge rates over the follow-up period were estimated using a PROC GENMOD procedure (A modified poisson regression approachto prospective studies with binary data)³ and a generalized estimating equation was performed to account for within-subject correlation. The Loess curves with a span of 0.15 were used to illustrate the estimated 10-day periods of arrhythmic events over time. The prediction of arrhythmic event 45-day after COVID-19 by predictors was performed by using logistic regression analysis. A p-value < 0.05 was considered as significant.

Baseline characteristics

A total of 33 patients (24 male 72,7%); mean age was 62,4±17,7 years) were enrolled in our study. All patients were using beta blockers and calcium channel blockers (dihydropyridine group). In the study, 51.5 percent of patients had an ICD implanted for primary prevention. In patients who had an ICD implanted for secondary prevention, 68,8% were implanted due to VT, 18,8 due to cardiac arrest and 12,4 due to syncope (Table 1).

Clinical events

Ventricular tachycardia events were analyzed by reviewing intracardiac EGM records. When looking at the records before gettting COVID-19, 7 (6 VT, 1 VF) arrhythmia episodes were detected. 5 of these arrhythmias were terminated by ATP and 2 by shock therapy. After the COVID-19 diagnosis, 20 arrhythmia (17 VT, 3 VF) episodes were detected. 14 of these arrhythmias were terminated by ATP and 6 by shock therapy (Table 2). Regarding the type of arrhythmia and the device therapy no statistical difference was found between the groups before and after COVID-19. Medication of patients with clinically significant arrhythmia episodes was rearranged. During the 6-month follow-up, there was only one arrhythmia episode in each patient.

Although none of 33 patients had VA episodes in 30 days prior to COVID-19, 14 (42,4%) of 33 patients had at least one arrhythmia episode treated by the ICD device in the first 30 days after COVID-19. Arrhythmias were detected in 7 patients both before and after COVID-19. The first severe VA after COVID-19 was seen on the 6th day. Serious arrhythmic events increased cumulatively and occurred on average 21,8±13,7 days post COVID-19. Kaplan-Meier curve analysis displayed that arrhythmic events after COVID-19 period were statistical significant before COVID-19 period (Log-rank p value <0,0001). 14 (70%) of 20 ventricular arrhythmia detected after COVID-19 were seen in the first month (Figures 1 and 2).

Comparing the incidence of arrhythmia in 3 months before and after COVID-19, it was seen that the risk of tachyarrhythmia increased 2.86 times, which is statistically significant according to paired analysis (95% confidence interval [CI] 1.57 to 5.19, p <0,0006). The number of all arrhythmic events including life-threatening and total sustained and nonsustained ventricular tachycardia/ fibrillation episodes was higher after the COVID-19 diagnosis [116 in the pre-COVID-19 period, and 400 mean in post-COVID-19(p value <0.001].

Compared with 45 days before covid-19, the risk of ventricular arrhythmias for the 45 days after covid-19 increased 9-fold (95% CI 2.44 to 33,2, p value: 0.001). Compared between 45-90 days before covid-19, the risk of ventricular arrhythmias for the 45 days after covid-19 increased 3,6-fold (95% CI 1.62 to 8, p value: 0.003) (Figure 2). According to the univariate logistic regression analysis adjusted for demographic and clinical parameters, demonstrated no significant relationship with arrhythmic events after COVID-19.

To the best of our knowledge, this is the first study to report the effect of COVID-19 on severe ventricular arrhythmia in patients with ICD devices. In many studies, it has been determined that cardiac arrhythmias increase in viral infections. Arrhythmia and conduction system disease are not early or common symptom of COVID-19 disease, and most symptoms in COVID-19 disease are associated with the respiratory system.⁴ Sinus tachycardia is the most common arrhythmia, and sinus tachycardia is a physiological response secondary to viral infection, and arrhythmias other than sinus tachycardia have been reported frequently and are typically caused by viral myocarditis affecting the cardiac conduction system.⁵ In particular, relatives of the current COVID-19 virus such as SARS and MERS tend to have many arrhythmias, including sinus bardicardia.^6,7 Arrhythmias in COVID-19 disease can also occur due to side effects of drugs, hypoxia and lung disease and myocarditis. Sinus bradycardia is one of the most common arrhythmias and can last for up to 2 weeks.⁸

In a study performed by Catherine J. O'Shea et al. a 32% reduction was observed in arrhythmias needing device therapy due to social isolation during the pandemic period and the decrease in real life stress factors. However, the COVID-19 status of the patients was not examined in this study. In our study, only patients with COVID-19 were included, and when the device records of the patients before and after COVD-19 were compared, a statistically significant increase was observed in ventricular arrhythmia and device therapy. In addition, in a study conducted by Biagio Sassone et al. it was objectively measured that the patients decreased their physical activities due to isolation during the pandemic period.⁹ In this study, a 25% decrease in the physical activities of patients who had an ICD for primary prevention was detected. Although a decrease in the incidence of arrhythmia was expected due to the decrease in physical activities, an increase in the number of arrhythmia was observed in our study. This may be due to the drugs used in the treatment of COVID-19, myocardial injury, hypoxia and pro-inflammatory mediators and COVID-19.

In this study, the level of COVID-19 treatment received by the patients was not evaluated (normal ward, intensive care, or use of a ventilator). Therefore, no relationship can be established between the severity of the disease and arrhythmic manifestations. Results from this study should be confirmed by future prospective studies or records.

The effects of the COVID-19 pandemic, especially on ventricular arrhythmia, have not been reported sufficiently. In our study, it was observed that life-threatening ventricular arrhythmias and device therapy increased in patients with COVID-19, especially in the first month after COVID-19. Cardiovascular symptoms of COVID-19 can range from mild troponin and BNP elevation to fulminant myocarditis, life-threatening venticular arrhythmia and refractory shock. Close hemodynamic and electrocardiographic follow-up should be performed for all patients with COVID-19, especially if they are under COVID-19 treatment. Furthermore, due to the isolation during the pandemic period, it is inevitable that cardiac patients with the ICD devices will have a decrease in the physical activities that should be done regularly and therefore, the metabolic and cardiovascular benefits of physical activity will disappear within a few weeks. Indoor regular personalized rehabilitation programs should be recommended to increase the cardiovascular condition of the patients.

Written Ethics approval and consent to participate was obtained by the Ethics Committees of the Van Training and Research Hospital when conducting this study.

Acknowledgements

Not applicable.

Authors’ contributions

TA and FS designed the research. MA and FS wrote the paper. AS and FS analyzed data. All authors reviewed the manuscript. All authors read and approved the fnal manuscript.

Funding

No funding was obtained for this study

Availability of data and materials

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

1. Adriano Nunes Kochi et al. Cardiac and arrhythmic complications in patients with COVID‐19. J Cardiovasc Electrophysiol. 2020 May;31(5):1003-1008. doi: 10.1111/jce.14479.

2. Catherine J. O’Shea et al. Ventricular arrhythmia burden during the coronavirus disease 2019 (COVID-19) pandemic. Eur Heart J. 2021 Feb 1;42(5):520-528. doi: 10.1093/eurheartj/ehaa893.

3. Zou, G. A modified poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004 Apr 1;159(7):702-6. doi: 10.1093/aje/kwh090.

4. Babapoor-Farrokhran S et al. Myocardial injury and COVID-19: possible mechanisms. Life Sci. 2020 Jul 15;253:117723. doi: 10.1016/j.lfs.2020.117723.

5. Kirmser R et al. Chest. 1977 May;71(5):682-4. doi: 10.1378/chest.71.5.682.

6. Yu CM et al. . Cardiovascular complications of severe acute respiratory syndrome. Postgrad Med J. 2006 Feb;82(964):140-4. doi: 10.1136/pgmj.2005.037515.

7. Saad M et al. Clinical aspects and outcomes of 70 patients with Middle East respiratory syndrome coronavirus infection: a single-center experience in Saudi Arabia. Int J Infect Dis. 2014 Dec;29:301-6. doi: 10.1016/j.ijid.2014.09.003.

8. Savalan Babapoor-Farrokhran et al. Arrhythmia in COVID-19. SN Compr Clin Med. 2020 Aug 14;1-6. doi: 10.1007/s42399-020-00454-2.

9. Biagio Sassone et al. Impact of COVID-19 Pandemic on Physical Activity in Patients With Implantable Cardioverter-Defibrillators. J Cardiopulm Rehabil Prev. 2020 Sep;40(5):285-286.doi: 10.1097/HCR.0000000000000539.

Table 1. Characteristics of the Study Population (N=33)

Age	62.4±17.7
Gender , %
Male	72.7
Female	27.3
Bmi	27.6±3.05
Comorbidities, %
CAD	57.6
DM	39.4
HT	66.7
COPD	9.1
Cigarette smoking, %	39.4
Medications, %
Diuretics	66.7
ACEI/ARB	100
ASA	78.8
Clopidogrel	9.1
Digoxin	24.2
Beta blockers	100
Cordarone	3
Calcium channel blockers	100
ICD indication, %
Primary prevention	51.5
Secondary prevention, %	48.5
VT	68.8
Cardiac arrest	18.8
Syncope/inducible VT	12.5
LV ejection fraction, %	36.9±10.2

CAD: Coronary artery disease, DM: Diabetes mellitus, HT: Hypertension, COPD: Chronic obstructive pulmonary disease, ACEI:Angiotensin-converting-enzyme inhibitors, ARB: Angiotensin receptor blockers, ASA: Acetylsalicylic acid, ICD: Implantable cardioverter-defibrillator, VT: Ventricular tachycardia, LV: Left ventricle.

Table 2. Characteristics of Ventricular Arrhythmias

Parameter	Before COVID-19	After COVID-19	p value
Arrhythmia type
Ventricular tachycardia (%) Ventricular fibrillation (%)	6/7 (85.7) 1/7(14.3)	17/20(85) 3/20(15)	NS NS
Termination (%)
ATP	5/7(71.4)	14(70)	NS
Shock	2/7(28.6)	6(30)	NS

COVID-19: Coronavirus disease 19, ATP: Antitachycardia pacing, NS: Not Statistically Significant

No competing interests reported.

Impact of COVID-19 Pandemic on Severe Ventricular Arrhythmia and Icd Therapy

Status:

Version 1

Abstract

Figures

Introduction

Methods

Inclusion criteria

Exclusion criteria

Statistical analysis

Results

Discussion

Limitations

Conclusion

Declarations

References

Tables

Additional Declarations

Status:

Version 1