key: cord-0963934-z2iyye56
authors: Amir, Muzakkir; Yoseph, Hendry; Farisi, Aulia Thufael Al; Phie, James Klemens Phieter; Adam, Andi Tiara Salengke
title: Symptomatic Bradycardia in Covid-19 Hospitalized Patients: a Case Series
date: 2021-07-29
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2021.07.068
sha: a9c9dee9717d7c366327b126adce55cc751760ea
doc_id: 963934
cord_uid: z2iyye56

SARS COV-2 infection has become a global threat, cardiovascular manifestations associated with Covid-19 has been noted in several publications, and bradycardia related to Covid-19 is a complication which is commonly reported. We reported six serial cases of bradycardia attributable to Covid-19. Four among them developed a complete atrioventricular block. These patients experienced clinical symptoms related to bradycardia initially required a permanent pacemaker implantation. One patient later however did not require permanent pacing due to spontaneous conversion to sinus rhythm. In comparison, the other two patients who developed transient sinus bradycardia experienced a self-limiting condition during their hospitalization period without requiring any cardiac pacing device nor medication to increase heart rate. Complete atrioventricular block and transient sinus bradycardia in these patients despite not having any history of bradycardia might be due to complex processes in the systemic inflammatory response in covid-19. Cardiac monitoring, hemodynamic evaluation, and strategy for permanent pacemaker in these patients should be treated as a case-by-case basis.

The novel human coronavirus (COVID-19) was first reported in Wuhan, China, and has become the fifth documented pandemic which has spread worldwide and is currently a global threat. (1) Arrhythmic events have become a part of cardiac manifestations related to Covid-19 infection that has been reported in multiple publications. (2) (3) (4) Bradycardia as a possible clinical feature in Covid-19 hospitalized patients is not well understood but studies suggest this condition to be due to multiple factors which include direct myocardial damage, inflammatory response, hypoxia, and down-regulation of ACE2. (5, 6) We report the increasing number of symptomatic bradycardia cases related to Covid-19 infection with no previous history of this condition during this pandemic era.

We identified six patients (66,7% women and 33,3% men, with mean age of 52,16 ± 16,55) who were admitted due to a Covid-19 infection who have shown respiratory illness and developed into symptoms related bradycardia, all patients were hospitalized at Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia during January 2021. All patients were diagnosed with SARS-COV2 infection in accordance with the guideline from the Indonesian Ministry of Health for diagnosing Covid-19 which is by polymerase-chain reaction on nasopharyngeal swab specimen. All patients were referred from remote areas in South Sulawesi due to limited facilities, and diagnosis confirmation of Covid-19 and symptoms associated with bradycardia was varied for each patient. Types of bradyarrhythmia were recorded using 12-lead Electrocardiogram (ECG). Baseline characteristics (patient demographics, clinical findings, laboratory results, and all related data during hospitalization) were collected and can be seen in Table 1 .

All patients were southeast Asians, three patients (60%) had comorbidities of hypertension, one patient (20%) had diabetes, one patient (16.7%) were obese with BMI >30 kg/m 2 , none of the patients had a previous history of heart rhythm disorders nor coronary artery disease and none of them were taking any anti-arrhythmic agent, all patients were presenting clinical symptoms related to bradycardia (lightheadedness, fatigue, near-syncope, and syncope), none of these patients require mechanical ventilation.

Laboratory parameters showed that all patients had an increased D-Dimer value that put all patients at risk of venous thromboembolism. NLR ratio, leukocytes, and platelets were varied among patients. Interestingly, this data revealed that each patient which were implanted with a pacemaker had a higher level of D-Dimer >3 times ULN (upper limit of normal). Chest X-Ray revealed four patients (66,6%) with bilateral pneumonia and two patients (33,3%) were normal, and from echocardiography examination, all patients shown no cardiac structural abnormality. All patients were taking azithromycin and an antiviral agent (Oseltamivir or Remdesivir) after being diagnosed with Covid-19, and none of these patients had a history of taking anti-arrhythmic agents.

All patients were admitted with respiratory illness (cough, dyspnea, fever) and required oxygen supplementation, all patients were referred from remote areas for further examination. On admission, patients underwent a 12-lead electrocardiogram (ECG). Additional laboratory tests were also conducted including high-sensitivity cardiac troponin I (hs-TnI) in which all of our patients showed no increase, therefore excluding a possible myocardial lesion.

Patient 1 revealed to have sinus bradycardia with PAC Bigemini with previous history of syncope.

This patient underwent permanent pacemaker implantation due to hemodynamic instability during hospitalization ( Figure 1 ). As for patient 2 and patient 6, both revealed to have a 3 rd -degree AV Block associated with syncope and near-syncope and developing hemodynamic instability therefore also underwent permanent pacemaker implantation (Figure 2 and 6) . Patient 3 also revealed to have developed a 3 rd -degree AV Block associated with near-syncope but has undergone temporary pacemaker prior to transfer to our hospital and encountered spontaneous resolution on 3 rd day of hospitalization (Figure 3) . From this patient we also found D-Dimer levels were slightly increased. Patient 4 and Patient 5 revealed to have sinus bradycardia with symptoms related to bradycardia, and during hospitalization, this patient did not develop any hemodynamic instability, and gradually showed clinical improvement during hospitalization and was discharged with an ECG showing regular heart rate without any symptoms. (Figure 4 

Bradycardia attributable to atrioventricular block or sinus node dysfunction in these patients require medical attention and closed monitoring were performed based on the patient's hemodynamic profile and ECG results. Patients with persistent complete atrioventricular block and sinus bradycardia with hemodynamic instability underwent permanent pacemaker implantation, and patients with sinus bradycardia without hemodynamic instability had a self-limiting condition during follow-up.

Cardiac arrhythmias, particularly bradycardia, has been noted in several studies and evidence of bradycardia which is related to infection, including severe pneumonia continue to emerge (7, 8) , the hypothesis that developed in describing the potential mechanism of cardiac arrhythmias include direct myocardial injury, hypoxia, hypotension, enhanced inflammatory response, angiotensin-converting enzyme-2 (ACE-2) receptor down-regulation (6, 9) , pro-inflammatory indicators such as IL-6 and D-dimer levels are thought to play a role in the systemic inflammation of Covid-19 and contributed in the cardiac manifestation of Covid-19 itself. (5, 10) Five of our patients showed increased levels of D-dimer that put them in a pro-inflammatory state. The European Society of Cardiology has guided permanent pacemaker implantation in a patient with complete atrioventricular block associated with Covid-19. It should be implemented until the patient is afebrile for more than 24 hours (11) . In contrast, the Italian Association of Hospital Cardiologists (ANMCO) has released a position paper which recommended an early permanent pacemaker implantation rather than a temporary pacemaker due to the risk of infection. (12) We implemented permanent pacemaker implantation due to documented complete AV-block with hemodynamic instability and history of pre-syncope and syncope, other considerations to implementing permanent pacemaker was to minimize the time of exposure and reduce hemodynamic consequences, and in addition, viral diseases rarely have been associated with cardiac implantable electronic device (CIED) infection. (11, 13) Transient sinus bradycardia in our patient was a self-limiting condition which did not require any CIED or medication to increase heart rate.

Our study reports short-term evaluation on symptomatic bradycardia patients with Covid-19.

Further research on other aspects such as long-term patient outcomes is needed to establish a better understanding of this condition.

We reported a case series of bradycardia associated with SARS COV-2 infection during this pandemic era. Our patients had either developed a complete atrioventricular block or transient sinus bradycardia without previously documented bradycardia, which might be due to a complex process in a systemic inflammatory response in Covid-19. During this pandemic era, the patient who developed cardiac rhythm disturbances and associated with respiratory illness should be suspected of SARS COV-2 infection, mainly in a remote area with limited resources. Cardiac monitoring, hemodynamic evaluation, and strategy for permanent pacemaker in these patients should be treated as a case-by-case basis.

Cardiac arrhythmia is one out of several other cardiac manifestations of SARS-COV2 infection and is presumed to be a multifactorial condition. These cardiac electrical disturbances in a Covid-19 patient should lead us into further enhanced electrophysiology study and other diagnostic methods to understand the underlying and exact pathomechanism of arrhythmias in SARS-COV 2 infection.

Cardiovascular complications of severe acute respiratory syndrome

Coronaviruses and the cardiovascular system: Acute and long-term implications

Cardiovascular disease and COVID-19

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19 . The COVID-19 resource centre is hosted on Elsevier Connect , the company ' s public news and information

European Heart Rhythm Association (EHRA) international consensus document on how to prevent, diagnose, and treat cardiac implantable electronic device infections -Endorsed by the Heart Rhythm Society (HRS), the Asia Pacific Heart Rhythm Society (APHRS), the Latin American Heart Rhythm Society (LAHRS), International Society for Cardiovascular Infectious Diseases (ISCVID) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS)

ANMCO POSITION PAPER: The management of suspect or confirmed COVID-19 patients needing urgent electrophysiology and/or electrostimulation procedures

Management of Pacemaker Implantation during COVID-19 Infection

Cardiovascular Implications of Fatal Outcomes of Patients with Coronavirus Disease 2019 (COVID-19)

Cardiac Arrhythmias in COVID-19 Infection

The Science Underlying COVID-19: Implications for the Cardiovascular System

Clinical analysis of sinus bradycardia in patients with severe COVID-19 pneumonia

Bradycardia in Patients With COVID-19: A Calm Before the Storm?

COVID-19: The first documented coronavirus pandemic in history

The authors do not have a conflict of interest to disclose.

This research received no specific funding.

Informed consent was obtained from all individual participants included in the study.

☒ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.