key: cord-0950883-cmddbnnl authors: Dagher, Lilas; Wanna, Bassam; Mikdadi, Ghiath; Young, Monique; Sohns, Christian; Marrouche, Nassir F title: High-degree atrioventricular block in COVID-19 hospitalized patients date: 2021-01-12 journal: Europace DOI: 10.1093/europace/euaa333 sha: 930dc0e2647a75c41a48342e8bafd65e1e36405a doc_id: 950883 cord_uid: cmddbnnl BACKGROUND: The novel coronavirus SARS-CoV-2 has shown the potential to significantly affect the cardiovascular system. Cardiac arrhythmias are commonly reported complications in COVID-19 hospitalized patients. METHODS: While tachyarrhythmias seem most common, we describe four cases of COVID-19 patients who developed a transient high-degree atrioventricular (AV) block during the course of their hospitalization. RESULTS AND CONCLUSION: All four patients who developed a high-degree AV block during their hospitalization with COVID-19 did not require permanent pacing. Similarly to most AV blocks associated with infectious organisms and given its transient nature, this case series suggests that conservative management strategies should be preferred in COVID-19 patients who develop complete heart block. The novel SARS-Cov2 virus, first described in Wuhan, China in late 2019, has quickly spread into a global pandemic causing. 1 Multiple reports have emerged implicating the cardiovascular (CV) system in this novel disease process. [2] [3] [4] [5] In one of the earliest published studies including 138 COVID-19 hospitalized patients from Wuhan, China, arrhythmias constituted the second most common complication after acute respiratory distress syndrome, with a rate of 16.7% and a notable increase to 44% in patients requiring intensive care. 6 Another study including two hospitals in New York City, the current global epicentre of the pandemic, reported an arrhythmia rate of 18.5% among patients requiring mechanical ventilation. 7 However, specific details regarding the type of arrhythmias encountered in COVID-19 patients are scarce. In this report, we describe a case series of four patients with no history of arrhythmia who developed intermittent high-degree atrioventricular (AV) block during the course of their hospitalization for COVID-19. Between March 2020 and April 2020, we identified four consecutive adult patients who were admitted for COVID-19 and who developed a complete heart block during their hospitalization at several medical centres in Louisiana, USA. Cases were reported from the following centres: the Louisiana Heart Center, Chalmette, LA, USA, and the North Oaks Medical Center, Hammond, LA, USA. All patients were diagnosed with COVID-19 in accordance with CDC guidelines, using real-time reverse transcriptase-PCR on a nasopharyngeal specimen collected by a healthcare professional. Atrioventricular block diagnosis was confirmed using a 12-lead electrocardiogram (ECG). Demographic, clinical, and laboratory data at admission and during their hospitalization were collected through a retrospective chart review. A waiver of informed consent was obtained due to the retrospective nature of the study. In this case series, we describe four patients (50% women, mean age 57.2 ± 10.2 years) diagnosed with COVID-19, who developed intermittent 3rd-degree AV block during their hospitalization. Detailed demographics, comorbidities, and clinical characteristics of each patient are reported in Table 1 . In summary, three patients of the four were African Americans. Three patients were >60 years old and had a history of hypertension. Obesity was only present in the youngest patient, aged 42 years old. Two patients had a history of type 2 diabetes and one patient had coronary artery disease. Two patients were on metoprolol. None of the patients had a history of cardiac arrhythmia or was taking amiodarone or digoxin. All patients presented to the emergency department with severe flu-like symptoms including cough, high fever, and dyspnoea requiring oxygen supplementation. No syncope or pre-syncope was reported at presentation. At baseline, Patients 1 and 2 had mild increase in troponin I levels (1.6 and 12 mg/mL, respectively), whereas Patients 3 and 4 presented with normal levels. Laboratory results showed elevated CRP ( Table 1) , and imaging data revealed diffuse bilateral pulmonary infiltrates in all patients. All four patients were transferred from the emergency department to a COVID-19 tele unit. The diagnosis of complete heart block was first made on telemetry, then confirmed with a 12-lead ECG. All patients were continuously observed on telemetry after diagnosis confirmation and until discharge. One example including telemetry and 12-lead ECG of Patient 1 is shown in Figure 1 . Her first episode starting on Day 2 of hospitalization was a 2nd-degree AV block Type II with 2:1 conduction, first observed on telemetry ( Figure 1A) , then confirmed with a 12-lead ECG, and followed by four additional episodes lasting between 15-20 s during the same day. The 2nd-degree AV block progressed to one episode of 3rd-degree heart block on Day 3. No specific new symptom was reported by the patient. No pharmacological treatment was initiated. The complete heart block spontaneously resolved thereafter ( Figure 1B) . She was discharged on Day 7 after complete symptomatologic recovery. On his first day of What's new? • Hospitalized COVID-19 patients can demonstrate a complete atrioventricular block without necessarily exhibiting a severe inflammatory profile. • Complete heart blocks occurring in our COVID-19 patients did not require permanent therapy, reflecting the transient nature of the infection. He remained haemodynamically stable. The complete heart block resolved spontaneously the following day. Patient 3 experienced three episodes of 3rd-degree heart block starting Day 2, each lasting 2-3 h. Her one-lead ECG strips during one episode of AV block and after resolution to sinus rhythm are shown in Figure 2 . All episodes were tolerated, and no further intervention was needed. Finally, Patient 4 started developing intermittent episodes of well-tolerated 3rd-degree AV block on Day 2 of hospital stay, lasting between 2 and 7 min. Metoprolol was immediately suspended. The bradyarrhythmia spontaneously resolved within 48 h. Hydroxychloroquine was initiated in this patient after the resolution of the heart block. None of the patients developed hypotension or haemodynamic instability associated with their intermittent complete heart block. Patients' ECG characteristics on presentation and at discharge are listed in Table 2 . During their hospital stay, all patients received a transthoracic echocardiogram, revealing normal cardiac function and valvular structure, with no signs suggestive of myocarditis or pericarditis. None of the patients was treated with hydroxychloroquine or an antiviral agent before or during their complete heart block episodes, nor required mechanical respiratory assistance. Cardiac management consisted of close rhythm monitoring through telemetry, suspension of AV blocking drugs, and only one patient required temporary cardiac pacing. All patients were discharged after 10-21 days from admission date with sinus rhythm and normal PR interval ( Table 2) , and close cardiology follow-up was recommended. In this case series, we describe the occurrence of a 3rd-degree AV block in four hospitalized patients diagnosed with COVID-19 and with no previous history of arrhythmia. Infectious organisms causing high-degree AV block are not frequent. Lyme disease patients can experience advanced AV block and diffuse conduction system disease, mainly due to the host inflammatory response directed at spirochetes in cardiac tissue, which are evident in interstitial space on microscopy. 8 In viral infections, the occurrence of complete heart block is extremely rare and there are only a few case reports in the literature describing complete heart block in viral myocarditis and even then, mainly in the paediatric population. 9 As for COVID-19 analogue infections, MERS and SARS, they have mainly been associated with tachyarrhythmias, with no reports of AV block among infected patients in the current literature. 10 One study published in 2006 examining 121 SARS patients showed a 18% rate of transient sinus bradycardia with a mean duration of 2.6 days, 11 similar to the overall duration of the complete heart block seen in our four patients. While most data support a tachyarrhythmic risk associated with COVID-19, this report describes the occurrence of transient 3rd-degree AV block in infected patients. In patients with COVID-19, one of the possible mechanisms of complete heart block includes a high systemic inflammatory burden 12 and cytokine storm causing ischaemic injury to myocardial cells and affecting the intrinsic conduction system whether it would be at the supra-Hisian or infra-Hisian level. Another possible mechanism involves a direct viral injury to the myocardium 10 and the conduction system itself manifesting as transient complete heart block. In fact, ACE2, the host receptor for SARS-CoV-2, is widely expressed not only in the lungs but also in the CV system and therefore, ACE2related signalling pathways could account for the immediate deleterious effect of the novel coronavirus on myocardial tissue, 10 regardless of the overall inflammatory burden. Viral myocarditis could also induce local inflammation, disrupting the cardiac conduction system. Nevertheless, no markers of myocarditis were observed in our patients. Moreover, COVID-19 patients are at high risk of developing acute renal failure, 13 which could cause major electrolyte disturbances and hyperkalaemia promoting AV block. In this case series, no renal failure was documented. Finally, COVID-19-associated heart block could be attributed to drug therapies and interactions, especially with the increase use of hydroxychloroquine. However, only one patient in this report was treated with hydroxychloroquine, which was initiated after the resolution of the complete heart block. Also, only the chronic use of hydroxychloroquine has been associated with severe cardiac bradyarrhythmia, 14 rendering this hypothesis less likely. Interestingly, the comorbidity burden was low among most of our described patients, and none had a history of arrhythmia. Hypertension was the only underlying comorbidity in two of the four patients who developed a 3rd-degree heart block. Patient 1, the youngest, suffered from obesity, a newly identified risk factor for COVID-19 complications in young patients. 15 Hypertension and obesity proved to be strong predictors of morbidity and mortality in COVID-19 patients, 15, 16 which could be explained by the fact that patients with these comorbidities can exhibit a high inflammatory state at baseline and an increase in serum ACE2 levels, predisposing to multi-organ damage. Notably, the only patient requiring cardiac pacing also had the highest comorbidity burden, which emphasizes the impact of baseline CV health on the severity of COVID-19 outcomes. Additionally, while the highest incidence of arrhythmia has been reported among intubated COVID-19 patients as previously mentioned, our patients experienced complete heart block without having critical symptoms, as none of them required mechanical ventilation support. This case series would suggest that inpatient cardiac monitoring of COVID-19 should target a broad population, without necessarily focusing on highly comorbid or severely symptomatic patients. This approach however remains challenging in overwhelmed hospital systems. The spontaneous resolution of the complete heart block in all patients reflects the transient nature of the viral infection and the inflammatory response associated with it. Long-term follow-up to assess for recurrent bradyarrhythmia may not seem necessary. However, scarce pathophysiological, 17 histological, 18 and imaging 19 data indicate that SARS-CoV-2 could induce durable tissue damage, which would predispose patients to recurrent arrhythmias long-term after discharge. No current study evaluates the long-term impact of COVID-19 on arrhythmias, thus clinical guidance regarding remote cardiac follow-up after discharge is considerably lacking. The predominance of African American patients in this case series (three of the four) most likely reflects the demographics of New Orleans and surrounding areas, as recent studies showed no difference in hospital outcomes and complications, including arrhythmia, between White and African American patients, [20] [21] [22] as well as no difference in ACE2 level expression. 23 Conclusions and future directions COVID-19 has shown the ability to promote arrhythmogenic complications, either through a severe inflammatory response or through a possible direct vial damage to the heart. The exact underlying mechanism remains to be postulated. While atrial fibrillation has been the most commonly documented arrhythmia, this report is one of the very few to describe high-degree AV block in several COVID-19-infected patients. The bradyarrhythmia was mostly transient and self-resolving. Further evaluation with invasive EP studies and endomyocardial biopsies if they can be performed safely both for the patient and without unnecessarily exposing staff to infection would be ideal to better understand the underlying pathophysiology. This case report can initiate investigation into whether the SARS-CoV-2 virus has a predilection to invade the conduction system itself and its long-term cardiac impact. Finally, further research is needed to better characterize the prevalence, type, and predictive factors of arrhythmias in COVID-19 patients and help in providing guidance for close cardiac follow-up during hospitalization and after their discharge. Conflict of interest: Authors do not have conflict of interest to disclose. The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. 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