key: cord-0955480-f1bjp16n authors: Gatto, Maria Chiara; Persi, Alessandro; Tung, Marzia; Masi, Rosa; Canitano, Stefano; Kol, Amir title: Bradyarrhythmias in patients with SARS‐CoV‐2 infection: A narrative review and a clinical report date: 2021-07-14 journal: Pacing Clin Electrophysiol DOI: 10.1111/pace.14308 sha: e92d1cd613615b7e7c048ca6c5743ffab2587a59 doc_id: 955480 cord_uid: f1bjp16n Several cardiovascular diseases and arrhythmic disorders have been described in COVID‐19 era as likely related to SARS‐CoV‐2 infection. The prognostic relevance of bradyarrhythmias during the infection has not been yet described and no data are available about long‐term heart conduction disorders. A review of literature concerning the association between hypokinetic arrhythmias and COVID‐19 from January 2020 to February 2021 was performed. The key‐words used for the research were: “sinus node disfunction,” “sick sinus syndrome (SSS),” “sino‐atrial block,” “atrio‐ventricular block (AVB),” “bradyarrhythmias,” and “COVID‐19″ or ”SARS‐CoV‐2.″ Excluding “relative bradycardia,” a total of 38 cases of bradyarrhythmia related to SARS‐CoV‐2 infection have been described, even in very young people, requiring in many cases a definitive pacemaker implantation. Furthermore, we report a case of non‐hospitalized 47‐years old man with a SSS developed as a consequence of mild SARS‐CoV‐2 infection. While in all described cases heart conduction disorders were found at presentation of the infection or during hospitalization for COVID‐19, in our case the diagnosis of SSS was made after the resolution of the infection. Although rarely, heart conduction disorders may occur during COVID‐19 and the present case highlights that a cardiological follow up may be desirable even after the resolution of infection, especially in the presence of symptoms suggesting a possible heart involvement. well-known risk factors for unfavorable outcomes during the course of SARS-CoV-2 infection, recently other arrhythmic disorders, including atrial fibrillation, have been recognized as additional markers of poor prognosis. 8, 9 Ventricular arrhythmias have also been reported; however often related to drug-induced lengthening of the QT interval. In particular, hydroxychloroquine, which has been widely used in the first wave of the ongoing pandemic, has been reported to cause arrhythmic storms. 10 Less commonly, hypokinetic arrhythmias such as sick sinus syndrome (SSS), atrio-ventricular block (AVB) and bundle branch block (BBB) have been described. [11] [12] [13] However, their role as potential prognostic markers has not been defined yet, suggesting the need of additional investigations. 14 We performed a review of updated literature regarding the association between hypokinetic arrhythmias and SARS-CoV-2 infection and also we report the case of a SSS in a previously healthy young man developing after the resolution of a mild SARS-CoV-2 infection. A review of current literature from January 2020 to February 2021 was performed. The studies were identified by searching electronic databases such as Pubmed and ScienceDirect. The key-words used for the research were: "sinus node disfunction," "SSS," "sino-atrial block," "AVB," "bradyarrhythmias," and " The bradyarrhythmias observed in COVID- 19 A total of 38 cases, derived from 23 articles, of hypokinetic arrhythmias in patients with SARS-CoV-2 infection have been described so far ( described, rarely associated with BBB (8%). The onset of cardiac conduction disorders was very variable, ranging from 0 to 30 days from hospitalization, with a median of 3.5 days. Although bradyarrhythmias are rarely described, relative bradycardia is a common characteristic in patients with SARS-CoV-2 infection. [38] [39] [40] [41] [42] The described bradyarrhythmias related to COVID-19 are summarized in Figure 3a and 3b. In the report of Chinitz et al. 5/7 (71%) of patients undergone definitive pacemaker implantation and leadless pacemaker was chosen as best option due to lower probability of device infection; in 2/7 (28%) patients a temporary or semipermanent pacemaker was implanted. 23 In this population 4/7 (57%) of patients died and the patients with definitive pacemaker implantation were 4/5 (80%); exitus occurred between 1 and 32 days after the procedure (median 9.5 days). A recent study reported a low percentage (9/700, 1.2%) of bradyarrhythmias in hospitalized patient with COVID-19, and these seem not be related to acute mortality. 11 In the present report we described 38 patients with bradyarrhythmias and we found that exitus occurred in 23.6% (9/38) of patients, among these, 7/9 (78%) with definitive pacemaker. The prognosis in patients with persistent bradyarrhythmias is not clearly defined, while some studies showed that clinical outcome (intensive care unit admission, intubation, death) was similar in patients with fever and relative bradycardia and in patients with fever and appropriate heart rate response. 41, 42 The percentage of pacemaker implantation in patients with heart conduction disorders and COVID-19, divided into those who survived and those who died, are reported in Figure 3c . Although not statistically significant, patients who did not survive to SARS-CoV-2 infection apparently more frequently had pacemaker implantation during hospitalization. Several cardiovascular diseases related to COVID-19 have been described so far, including, although rarely, bradyarrhythmias and heart conduction disorders such as bundle branch blocks, with the latter correlating with worse prognosis. [11] [12] [13] Moreover, the lack of the physiological heart rate increase during fever, named as "relative bradycardia," has been shown to represent an early sign of SARS-CoV-2 infection. 11, 41 This condition had yet an acknowledged diagnostic significance in infectious diseases and has been associated also with typhoid fever, Legionnaire's disease, leptospirosis and certain viral infections. 43, 44 Some years ago, relative bradycardia was described also during Middle Eastern respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS), more often related to medications as ribavirin and sometimes was related to poor prognosis. 45 From the available data in the literature, it is still unknown whether it is necessary to implant a permanent pacemaker and which would be the optimal timing of the procedure. Since we could not define with certainty the stability of the arrhythmic condition of our patient, and considering that he had never experienced syncope, we decided to implant a loop recorder with home monitoring in order to closely unveil the occurrence of severe bradyarrhythmias events which might subsequently require a definitive pacemaker implantation. The occurrence of heart conduction alterations following asymptomatic or mild COVID-19, as it happened in our case, should focus the attention towards possible late sequelae of SARS-COV-2 infection, suggesting that the virus itself should be considered an additional risk factor for cardiovascular disease. The case herein presented highlights that cardiological evaluation during follow-up of outpatients with previous SARS-CoV-2 infection may be desirable, especially in the presence of symptoms suggesting a possible heart involvement. Although the proposal may seem unsustainable during a pandemic, it is also known that a not negligible rate of patients still experience symptoms (i.e., fatigue, pre-syncope, shortness of breath) even after SARS-CoV-2 infection resolution, and this is true not only for severe but also for mild infections, as it is the present case. Therefore, in order to screen for heart rhythm disorders a cardiological follow up may be reasonable in these patients. In conclusion, heart conduction disorders may occur during the course of COVID-19 and, although less commonly, even after resolution of SARS-CoV-2 infection. The decision to pacemaker implantation should be based on accurate analysis aimed at evaluating the reversibility of this disorder, especially in young patients. Data are available upon request from corresponding author. Maria Chiara Gatto MD, PhD https://orcid.org/0000-0002-6830- SARS-CoV-2 infection and cardiovascular disease: COVID-19 heart Cardiovascular complications in COVID-19 Nox2 activation in Covid-19 Researchers investigate what COVID-19 does to the heart COVID-19 and cardiovascular disease: from basic mechanisms to clinical perspectives COVID-19-Induced cytokine release syndrome associated with pulmonary vein thromboses, atrial cardiomyopathy, and arterial intima inflammation Hypoalbuminemia, coagulopathy, and vascular disease in COVID-19 Atrial fibrillation in the COVID-19 era: simple bystander or marker of increased risk? Should atrial fibrillation be considered a cardiovascular risk factor for a worse prognosis in COVID-19 patients? Electrical storm in a patient with COVID -19 treated with hydroxychloroquine: a case report Cardiac arrhythmias in patients with COVID-19 COVID-19 and cardiac arrhythmias Arrhythmias and COVID-19 Wide QRS complex and lateral ST-T segment abnormality are associated with worse clinical outcomes in COVID-19 patients Atypical presentation of COVID-19 as subclinical myocarditis with persistent high-degree atrioventricular block treated with pacemaker implant Complete heart block, severe ventricular dysfunction, and myocardial inflammation in a child with COVID-19 infection Transient complete heart block in a patient with critical COVID-19 Heart block in patients with coronavirus disease 2019: a case series of 3 patients infected with SARS-CoV-2. HeartRhythm Case Rep Incomplete trifascicular block and mobitz type II atrioventricular block in COVID-19 A case report of a rare cardiac complication in novel coronavirus disease Highgrade heart block requiring transvenous pacing associated with multisystem inflammatory syndrome in children during the COVID-19 pandemic Bradyarrhythmias in patients with COVID-19: marker of poor prognosis? Sinus node dysfunction in a young patient with COVID-19 COVID-19 patient with symptomatic bradycardia COVID-19 treatment with lopinavir-Ritonavir resulting in sick sinus syndrome: a case report COVID-19 e coinvolgimento cardiaco: una presentazione inusuale Novel coronavirus 19 (COVID-19) associated sinus node dysfunction: a case series Cardiac arrhythmias in COVID-19 infection Atrioventricular and sinus node dysfunction in stable COVID-19 Patients. SN Compr Bradyarrhythmias in patients with COVID-19: a case series Case report: high-grade atrioventricular block in suspected COVID-19 myocarditis Management of pacemaker implantation during COVID-19 infection A case of complete heart block in a COVID-19 infected patient The pathogenesis and treatment of the 'cytokine storm' in COVID-19 Interleukin-6 impairs chronotropic responsiveness to cholinergic stimulation and decreases heart rate variability in mice Relative bradycardia in patients with mild-to-moderate coronavirus disease Clinical analysis of sinus bradycardia in patients with severe COVID-19 pneumonia Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic Management of arrhythmias associated with COVID-19 Relative bradycardia in patients with COVID-19 Prevalence and clinical significance of relative bradycardia at hospital admission in patients with coronavirus disease 2019 (COVID-19) The diagnostic significance of relative bradycardia in infectious disease The clinical significance of relative bradycardia Efficacy and safety of current therapeutic options for COVID-19-Lessons to be learnt from SARS and MERS epidemic: a systematic review and meta-analysis Adverse events associated with high-dose ribavirin: evidence from the Toronto outbreak of severe acute respiratory syndrome Bradyarrhythmias in patients with SARS-CoV-2 infection: A narrative review and a clinical report