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Prevalence, Management, and Outcome of Atrial Fibrillation and Other Supraventricular Arrhythmias in COVID-19 Patients

Published:January 22, 2022DOI:https://doi.org/10.1016/j.ccep.2021.10.001

      Keywords

      Key points

      • Supraventricular arrhythmias are common in COVID-19 patients, especially in critically ill.
      • Arrhythmias occur after direct viral damage, but also due to systemic involvement.
      • Atrial fibrillation represents the most common supraventricular arrhythmias and it is independently associated with in-hospital mortality.
      • Supraventricular arrhythmias will be safely treated, minimizing exposure and paying attention to general clinical conditions.

      Introduction

      Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is the causative agent of coronavirus disease 2019 (COVID-19); it was officially detected for the first time in Wuhan and has spread throughout the world becoming a pandemic.
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      Although COVID-19 causes respiratory symptoms in most patients, several studies showed an extrapulmonary involvement, including the cardiovascular system.
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      Evidence of systemic endothelial injury and Microthrombosis in hospitalized COVID-19 patients at different Stages of the disease.
      COVID-19 patients may be affected by myocarditis, thromboembolic events, heart failure and cardiogenic shock, acute coronary syndromes, and atrial and ventricular arrhythmias.
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      Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic.
      Notably, cardiac arrhythmias occur in 6% to 17% of patients, rising to 44% in patients admitted to the intensive care unit,
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      Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus–infected pneumonia in Wuhan, China.
      resulting the second most frequent complication after acute respiratory distress syndrome.
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      Cardiovascular risks in patients with COVID-19: potential mechanisms and areas of uncertainty.
      Several possible mechanisms lead to an increased risk of cardiac arrhythmias during COVID-19 infection, ranging from direct myocardial injury to extracardiac involvement.
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      Arrhythmias and COVID-19.
      Arrhythmias are mainly caused by the hypoxia related to direct viral damage in the lungs, myocarditis, or abnormal inflammatory response and secondarily as a result of myocardial ischemia, myocardial strain, or electrolyte imbalances.
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      Arrhythmias and COVID-19.
      As a matter of fact, arrhythmias are not simply caused by the direct effect of COVID-19 infection, but instead are probably the result of a multifactorial condition.
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      COVID-19 and cardiac arrhythmias.
      Supraventricular arrhythmias are the most frequent arrhythmias observed in COVID-19 patients and among them, atrial fibrillation (AF) is the most common occurring in about 15% to 30% of them.
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      Cardiac electrophysiology consultative experience at the epicenter of the COVID-19 pandemic in the United States.
      The presence of AF is associated with increased clinical manifestations of severe COVID-19 and is independently associated with in-hospital mortality, posing a significant burden to patients, physicians, and health care systems globally.
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      • Manocha K.K.
      • Ying X.
      • et al.
      Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19.
      The complexity of this clinical condition requires a multifaceted and multidisciplinary approach; thus, we provide a comprehensive guidance for monitoring and management of cardiac arrhythmias in COVID-19 patients.

      Mechanisms of arrhythmogenesis in COVID-19

      COVID-19 infection can lead to an increased risk of cardiac arrhythmias by several pathophysiological mechanisms, which are summarized in Fig. 1. These include different types of myocardial injury and extracardiac processes that may exacerbate arrhythmias in patients with a pre-existing propensity.
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      Figure thumbnail gr1
      Fig. 1Potential mechanisms of arrhythmia and COVID-19. IL, interleukin; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

       Hypoxia

      The most recurrent COVID-19 manifestation is respiratory involvement, which may progress to acute respiratory distress syndrome. Hypoxia results in anaerobic glycolysis causing a decrease of intracellular pH and electrolyte imbalance, mainly an increase of calcium levels.
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      • Capecchi P.L.
      COVID-19, arrhythmic risk, and inflammation: mind the gap.
      A higher cytosolic Ca2+ concentration alters cellular action potentials and contribute to the development of early and late afterdepolarizations, which are a known trigger for atrial and ventricular arrhythmias.
      • Lazzerini P.E.
      • Boutjdir M.
      • Capecchi P.L.
      COVID-19, arrhythmic risk, and inflammation: mind the gap.
      Anaerobiosis also results in an increased potassium concentration and, as a consequence, increased cellular excitability and electrical conduction velocity.
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      • Capecchi P.L.
      COVID-19, arrhythmic risk, and inflammation: mind the gap.
      In addition, hypoxia reduces electrical coupling and tissue anisotropy via inactivation of connexin-43 in the gap junctions.
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      Coronary artery disease and ventricular Tachyarrhythmia: pathophysiology and treatment.
      Moreover, respiratory failure causes a hyperadrenergic tone, which contributes to the risk of cardiac arrhythmias.
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      Coronavirus Fulminant myocarditis treated with glucocorticoid and human Immunoglobulin.
      Indeed, hypersympathetic activity leads to an amplified calcium influx into cardiomyocytes, resulting in a calcium overload and frequently delayed afterdepolarizations.
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      Calcium in the pathophysiology of atrial fibrillation and heart failure.

       Myocarditis

      Several findings suggest that SARS-CoV-2 is the causative agent of myocarditis and that myocardium involvement may occur by direct virus infection or through infected alveolar macrophages.
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      Association of cardiac infection with SARS-CoV-2 in confirmed COVID-19 autopsy cases.
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      • Muser D.
      • et al.
      Recognizing COVID-19–related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management.
      The virus penetrates the myocardial cell, binding the receptors of the angiotensin-converting enzyme-2 (ACE-2) that will be internalized, leading to a consequent inhibition of angiotensin II degradation.
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      Cryo-EM structure of the 2019-NCoV spike in the prefusion conformation.
      ,
      • South A.M.
      • Diz D.I.
      • Chappell M.C.
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      The downregulation of myocardial ACE-2 expression is associated with excessive accumulation of angiotensin II, which causes myocardial injury, remodeling, and even adverse cardiac outcomes.
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      • Kassiri Z.
      • Jiang C.
      • et al.
      SARS-coronavirus Modulation of myocardial ACE2 expression and inflammation in patients with SARS.
      Thus, downregulation of ACE-2 in COVID-19 might increase AF vulnerability and its perpetuation.
      Another potential mechanism is that virus-activated CD8+ T lymphocytes reach the myocardium and can cause myocardial inflammation, as a result of the release of proinflammatory cytokines and activation of T lymphocytes.
      • Siripanthong B.
      • Nazarian S.
      • Muser D.
      • et al.
      Recognizing COVID-19–related myocarditis: the possible pathophysiology and proposed guideline for diagnosis and management.
      In the acute phase of myocarditis, arrhythmogenesis is caused by cellular damage, ionic imbalance, and gap junction dysfunction due to impaired cardiac connexin expression.
      • Tse G.
      • Yeo J.M.
      • Chan Y.W.
      • et al.
      What is the arrhythmic Substrate in viral myocarditis? Insights from clinical and animal studies.
      In myocarditis, inflammation leads to impaired cellular calcium and potassium homeostasis, producing early and delayed afterdepolarizations and increasing cellular repolarization and conduction time.
      • Tse G.
      • Yeo J.M.
      • Chan Y.W.
      • et al.
      What is the arrhythmic Substrate in viral myocarditis? Insights from clinical and animal studies.
      Prolonged repolarization time leads to triggered activity, whereas coupling with increased conduction time leads to re-entry circuits.
      • Tse G.
      • Yeo J.M.
      • Chan Y.W.
      • et al.
      What is the arrhythmic Substrate in viral myocarditis? Insights from clinical and animal studies.

       Myocardial Ischemia

      Myocardial ischemia in COVID-19 patients could be caused by coronary dysfunction and hyperinflammatory response.
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      • et al.
      Endothelial cell dysfunction: a major player in SARS-CoV-2 infection (COVID-19)?.
      The release of cytokines promotes the activation of T lymphocytes and monocytes within a pre-existing atherosclerotic plaque; the resulting histotoxic effect may cause plaque rupture, thereby leading to an acute coronary syndrome. Moreover, the release of the aforementioned cytokines, specifically interleukin (IL)-6, may exert proatherogenic effects, characterized by vascular smooth muscle proliferation, endothelial cell, and platelet activation.
      • Madjid M.
      • Vela D.
      • Khalili-Tabrizi H.
      • et al.
      Systemic infections cause exaggerated local inflammation in atherosclerotic coronary arteries: clues to the triggering effect of acute infections on acute coronary syndromes.
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      Endothelium as a predictor of adverse outcomes: endothelium as a predictor of adverse outcomes.
      Myocardial ischemia can also be caused by microvascular dysfunction due to endothelial impairment.
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      • Corrales-Medina V.F.
      Acute infection and myocardial Infarction.
      ,
      • Della Rocca D.G.
      • Pepine C.J.
      Some Thoughts on the continuing dilemma of angina pectoris.
      Endothelial dysfunction in COVID-19 patients is caused primarily by the downregulation of ACE-2 receptors, triggering the kallikrein-bradykinin system and resulting in increased vascular permeability.
      • Pober J.S.
      • Sessa W.C.
      Evolving Functions of endothelial cells in inflammation.
      Neutrophils and T lymphocytes release inflammatory cytokines and vasoactive molecules increasing endothelial cell contractility and vascular permeability.
      Virus-mediated vasculitis is another possible mechanism of microvascular dysfunction because the virus penetrates vascular endothelial cells via ACE-2 receptors, leading to inflammation and apoptosis.
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      • Flammer A.J.
      • Steiger P.
      • et al.
      Endothelial cell infection and endotheliitis in COVID-19.

       Cytokine Storm

      COVID-19 infection causes systemic inflammation and hyperactivation of lymphocytes and monocytes cells, resulting in a cytokine storm (IL-1b, IL-2, IL-6, IL-7, and interferon-γ) and an imbalance between lymphocytes T-helper-1 and T-helper-2 cells.
      • Huang C.
      • Wang Y.
      • Li X.
      • et al.
      Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China.
      Distinctive cytokines have been shown to induce AF: tumor necrosis factor-α (TNF-α) increases AF vulnerability and exerts direct effects on atrial structural and electrical remodeling
      • Lee S.-H.
      • Chen Y.-C.
      • Chen Y.-J.
      • et al.
      Tumor Necrosis factor-α alters calcium handling and increases arrhythmogenesis of pulmonary vein cardiomyocytes.
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      Increased atrial arrhythmia Susceptibility induced by Intense endurance exercise in Mice requires TNFα.
      • Mohanty S.
      • Trivedi C.
      • Della Rocca D.G.
      • et al.
      Thromboembolic risk in atrial fibrillation patients with left atrial scar post-extensive ablation.
      ; TNF-α and IL-1β may impair cardiac contractility, which is a known risk factor for arrhythmogenesis; IL-6 reduces cardiac connexins and promotes electrical remodeling during acute inflammation.
      • Lazzerini P.E.
      • Laghi-Pasini F.
      • Acampa M.
      • et al.
      Systemic inflammation Rapidly induces Reversible atrial electrical remodeling: the role of interleukin-6–mediated changes in connexin expression.
      ,
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      • Trivedi C.
      • et al.
      Association of Fragmented QRS with left atrial Scarring in patients with persistent atrial fibrillation undergoing Radiofrequency catheter ablation.
      Furthermore, IL-6, TNF-α, and IL-1 can lead to prolongation of the cardiac action potential due to impairment of K+ and Ca2+ channels.
      • Puntmann V.O.
      • Taylor P.C.
      • Barr A.
      • et al.
      Towards understanding the phenotypes of myocardial involvement in the presence of Self-limiting and Sustained systemic inflammation: a Magnetic Resonance Imaging study.

       Electrolyte Imbalance and Fluid Overload

      Electrolyte abnormalities are a well-known trigger of arrhythmogenesis.
      • El-Sherif N.
      • Turitto G.
      Electrolyte disorders and arrhythmogenesis.
      In a study of 416 hospitalized patients with COVID-19 infection, 7.2% of patients had electrolyte disturbances, such as hypokalemia, hypomagnesemia, and hypophosphatemia.
      • Shi S.
      • Qin M.
      • Shen B.
      • et al.
      Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China.
      In particular, hypokalemia is very frequent in patients with COVID-19, affecting up to 61% of hospitalized patients.
      • Chen D.
      • Li X.
      • Song Q.
      • et al.
      Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China.
      These electrolyte imbalances were primarily caused by COVID-19–associated diarrhea and renal impairment.
      • Shi S.
      • Qin M.
      • Shen B.
      • et al.
      Association of cardiac injury with mortality in hospitalized patients with COVID-19 in Wuhan, China.
      Indeed, in a retrospective study of hospitalized patients with COVID-19 infection, 27% of patients had acute renal failure.
      • Diao B.
      • Wang C.
      • Wang R.
      • et al.
      Human Kidney is a Target for novel severe acute respiratory syndrome coronavirus 2 infection.
      In addition, SARS-CoV-2 causes downregulation of ACE-2 receptors and thereby reduces the feedback effects of ACE-2 on the renin-angiotensin-aldosterone system.
      • Chen D.
      • Li X.
      • Song Q.
      • et al.
      Assessment of hypokalemia and clinical characteristics in patients with coronavirus disease 2019 in Wenzhou, China.
      This leads to increased reabsorption of sodium and water, resulting in increased blood pressure and excretion of potassium. The resulting hypokalemia causes hyperpolarization of the myocardiocytes, predisposing to atrial arrhythmias.
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      • Heeringa J.
      • Kors J.A.
      • et al.
      Serum potassium levels and the risk of atrial fibrillation.

      Supraventricular tachycardia prevalence and outcome

      Supraventricular arrhythmias are the most frequent arrhythmias among COVID-19 patients.
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      • Melki L.
      • et al.
      Management of arrhythmias associated with COVID-19.
      ,
      • Chen Q.
      • Xu J.
      • Gianni C.
      • et al.
      Simple electrocardiographic criteria for Rapid Identification of Wide QRS complex Tachycardia: the new limb lead algorithm.
      In a recent worldwide survey, about 18% of enrolled patients developed any arrhythmias
      • Coromilas E.J.
      • Kochav S.
      • Goldenthal I.
      • et al.
      Worldwide survey of COVID-19–associated arrhythmias.
      : most of them were supraventricular arrhythmias (81.3%), AF representing the most common (61.5%). In another retrospective study, 166 patients experienced atrial arrhythmias (15.8%) and newly diagnosed atrial arrhythmias occurred in 101 patients (9.6%), corroborating the central role of virus infection in the pathogenesis of cardiac arrhythmias.
      • Peltzer B.
      • Manocha K.K.
      • Ying X.
      • et al.
      Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19.
      Overall, a recent meta-analysis demonstrated that the occurrence of supraventricular arrhythmias was more frequent in critically ill patients (relative risk: 12.1; 95% confidence interval, 8.5–17.3), in particular those treated with invasive mechanical ventilation.
      • Goyal P.
      • Choi J.J.
      • Pinheiro L.C.
      • et al.
      Clinical characteristics of covid-19 in New York city.
      ,
      • Garcia-Zamora S.
      • Lee S.
      • Haseeb S.
      • et al.
      Arrhythmias and electrocardiographic findings in coronavirus disease 2019: a Systematic review and meta-analysis.
      The occurrence of supraventricular arrhythmias is associated with worse outcomes. Indeed, hospital admission in the intensive care unit and thromboembolic risk (pulmonary embolism, stroke, or deep vein thrombosis) was higher in COVID-19 patients with atrial arrhythmia than the general population.
      • Zareini B.
      • Rajan D.
      • El-Sheikh M.
      • et al.
      Cardiac arrhythmias in patients hospitalized with COVID-19: the ACOVID study.
      Therefore, giving the critical conditions of these patients, it is not unexpected that AF should be considered as an independent predictor of 30-day mortality (adjusted odds ratio: 1.93; P = .007).
      • Peltzer B.
      • Manocha K.K.
      • Ying X.
      • et al.
      Outcomes and mortality associated with atrial arrhythmias among patients hospitalized with COVID-19.

      Management of supraventricular arrhythmias

      The correct management of supraventricular arrhythmias has a central role in COVID-19 patients, especially those hospitalized with more severe forms of the disease and whose outcomes strictly depend on hemodynamic stability. Although there are few studies about the treatment of arrhythmia in COVID-19 patients, it is necessary to take particular attention to the paroxysmal features of arrhythmias, drug-drug interactions, and limitation of exposure.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      ,
      • Saenz L.C.
      • Miranda A.
      • Speranza R.
      • et al.
      Recommendations for the organization of electrophysiology and cardiac pacing Services during the COVID-19 pandemic: Latin American heart rhythm Society (LAHRS) in collaboration with: Colombian college of electrophysiology, argentinian Society of cardiac electrophysiology (SADEC), Brazilian Society of cardiac arrhythmias (SOBRAC), Mexican Society of cardiac electrophysiology (SOMEEC).
      Given the overwhelming prevalence of AF and atrial flutter (AFL) in patients with COVID-19, we will focus on the treatment of these arrhythmias.

       Rhythm Control

      Patients with hemodynamic instability due to new-onset AF and AFL should undergo electrical cardioversion (Fig. 2). The choice for electrical cardioversion inevitably involves the need for personnel at bedside, and the possibility of invasive mechanical ventilation, that would increase the development of viral aerosols.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      Intravenous infusion of amiodarone is recommended for rhythm control in critically ill patients.
      • Saenz L.C.
      • Miranda A.
      • Speranza R.
      • et al.
      Recommendations for the organization of electrophysiology and cardiac pacing Services during the COVID-19 pandemic: Latin American heart rhythm Society (LAHRS) in collaboration with: Colombian college of electrophysiology, argentinian Society of cardiac electrophysiology (SADEC), Brazilian Society of cardiac arrhythmias (SOBRAC), Mexican Society of cardiac electrophysiology (SOMEEC).
      ,
      • Goldschlager N.
      • Epstein A.E.
      • Naccarelli G.V.
      • et al.
      A practical guide for clinicians who treat patients with amiodarone: 2007.
      Moreover, we should be aware of the combination of amiodarone with hydroxychloroquine and/or azithromycin, as the benefit of the eventual combination has to be weighed against the arrhythmic risk caused by QT prolongation.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      ,
      • Russo V.
      • Carbone A.
      • Mottola F.F.
      • et al.
      Effect of Triple combination therapy with lopinavir-ritonavir, azithromycin, and hydroxychloroquine on QT Interval and arrhythmic risk in hospitalized COVID-19 patients.
      All interactions between medications for AF and COVID-19 are summarized in Table 1.
      Figure thumbnail gr2
      Fig. 2Acute treatment of AF and AFL in COVID-19 patients. AF, atrial fibrillation; AFL, atrial flutter.
      Table 1Interactions between medications for AF and COVID-19
      Rate Control DrugsRemdesivirHydroxychloroquineAzithromycin
      β-Blockers
       Atenolol---
       Bisoprolol---
       Metoprolol---
       Propranolol---
      Nondihydropyridine calcium channel blockers
       Diltiazem---
       Verapamil--
       Others
       Digoxin-↑↑-
      Rhythm control drugs
       Amiodarone-↑↑↑↑↑↑
       DronedaroneNo data available↑↑↑↑↑↑
       Flecainide-↑↑↑↑↑
       Propafenone--↑↑↑
      Oral anticoagulants
       Apixaban-↑↑
       Edoxaban-↑↑↑↑↑
       Rivaroxaban-↑↑
       Dabigatran-↑↑↑↑
       Warfarin---
      ↑↑↑: Potential substantially increased exposure of the medications; these drugs should not be prescribed together.
      ↑↑: Potential moderately increased exposure of the medications; dosage adjustment or close monitoring may be required.
      ↑: Potential mildly increased exposure of the medications; the interactions are weak.
      -: No significant effects.
      Class IC antiarrhythmic agents should be administered with great caution because of their arrhythmogenic and negative inotropic effect, especially in critically ill COVID-19 patients, who are prone to or have already developed myocarditis and heart failure.
      • Lavalle C.
      • Trivigno S.
      • Vetta G.
      • et al.
      Flecainide in ventricular arrhythmias: from old Myths to new perspectives.
      Because of possible increases in plasma concentration of flecainide when co-administered with hydroxychloroquine and lopinavir/ritonavir and/or the potential QT-prolonging effects of these drugs, serial ECG monitoring is recommended before and after initiating drug therapy.
      However, the only rhythm control strategy is not sufficient to achieve a long-term benefit in patients with acute respiratory failure, if the other existing comorbidities (eg, hypoxemia, inflammation, electrolyte imbalances, metabolic acidosis, volume overload, increased sympathetic tone, bacterial superinfection) are not properly treated.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      ,
      • Ganatra S.
      • Dani S.S.
      • Shah S.
      • et al.
      Management of cardiovascular disease during coronavirus disease (COVID-19) pandemic.
      In stable hospitalized patients with AF, antiarrhythmic drugs (such as sotalol, flecainide, amiodarone, and propafenone) should be discontinued and rate control therapy initiated with beta-blockers (or nondihydropyridine calcium channel blockers, unless contraindicated, with or without digoxin) because these drugs represent a safer option when administered in combination with an antiviral therapy.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      The combination of verapamil with hydroxychloroquine should be avoided because both drugs exert a negative effect on sinoatrial and atrioventricular nodes causing bradycardia and conduction disturbances.
      • Capel R.A.
      • Herring N.
      • Kalla M.
      • et al.
      Hydroxychloroquine reduces heart rate by Modulating the hyperpolarization-activated current if: novel electrophysiological Insights and therapeutic potential.
      Therefore, ECG monitoring for bradycardia and conduction disturbance should be considered. All interactions between medications for AF and COVID-19 are summarized in Table 1.

       Anticoagulation Therapy

      In COVID-19 patients, anticoagulation is prescribed according to the CHA2DS2-VASc score.
      • Hindricks G.
      • Potpara T.
      • Dagres N.
      • et al.
      2020 ESC guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European association for cardio-Thoracic Surgery (EACTS).
      It is important to highlight that some drugs for the treatment of COVID-19 infection have significant interactions with direct oral anticoagulants (DOACs; Table 1).
      • Agarwal S.
      • Agarwal S.K.
      Lopinavir-Ritonavir in SARS-CoV-2 infection and drug-drug interactions with cardioactive medications.
      In particular, lopinavir and ritonavir may have interactions with cytochrome P450 CYP3A4 and antimalarial drugs through P-glycoprotein inhibition.
      • Testa S.
      • Prandoni P.
      • Paoletti O.
      • et al.
      Direct oral anticoagulant plasma levels’ Striking increase in severe COVID-19 respiratory syndrome patients treated with antiviral agents: the cremona experience.
      In these cases, DOACs should be avoided to reduce the risk of bleeding.
      • Gawałko M.
      • Kapłon-Cieślicka A.
      • Hohl M.
      • et al.
      COVID-19 associated atrial fibrillation: Incidence, putative mechanisms and potential clinical Implications.
      In general, DOACs should be favored over vitamin K antagonists (VKAs), given their better safety profile and the standard, international normalized ratio-independent dosing modalities.
      • Lavalle C.
      • Di Lullo L.
      • Bellasi A.
      • et al.
      Adverse drug Reactions during Real-life use of direct oral anticoagulants in Italy: an update Based on data from the Italian national pharmacovigilance network.
      Indeed, VKAs treatment requires regular monitoring of the international normalized ratio,
      • Holbrook A.
      • Schulman S.
      • Witt D.M.
      • et al.
      Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-Based clinical practice guidelines.
      increasing contact with medical staff, so VKAs should be used preferably only in patients with mechanical prosthetic valves or antiphospholipid syndrome.
      • Holbrook A.
      • Schulman S.
      • Witt D.M.
      • et al.
      Evidence-based management of anticoagulant therapy: antithrombotic therapy and prevention of thrombosis, 9th ed: American college of chest physicians evidence-Based clinical practice guidelines.
      Heparins have no pharmacologic interactions with drugs for the treatment of COVID-19, making them a safe alternative to oral anticoagulants. Moreover, heparin could provide an anti-inflammatory role in addition to its anticoagulant effect. In fact, heparan sulfate proteoglycans, binding to SARS-CoV-2 spike proteins, decrease host protein binding capability and reduce cytokine cascade.
      • Yu M.
      • Zhang T.
      • Zhang W.
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      Elucidating the interactions between heparin/heparan Sulfate and SARS-CoV-2-related proteins—an important strategy for developing novel therapeutics for the COVID-19 pandemic.

       Echocardiography

      Regarding instrumental examinations in COVID-19 patients, the use of echocardiogram should be limited in order to limit unnecessary contacts among health care providers and patients.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      Echocardiography should be performed only if crucial for immediate therapeutic management of critically ill patients.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      In this case, transthoracic echocardiography must be chosen over transesophageal echocardiography, thereby avoiding the creation of aerosols.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      ,
      • Irons J.F.
      • Pavey W.
      • Bennetts J.S.
      • et al.
      COVID-19 safety: aerosol-generating procedures and cardiothoracic Surgery and anaesthesia - Australian and New Zealand consensus Statement.
      Transesophageal echocardiography should be avoided for early initiation of anticoagulation in new-onset AF, or maintenance of anticoagulant therapy in patients with known AF.
      • Gedikli Ö.
      • Mohanty S.
      • Trivedi C.
      • et al.
      Impact of dense “Smoke” detected on Transesophageal echocardiography on stroke risk in patients with atrial fibrillation undergoing catheter ablation.
      Cardiac computed tomography may be an alternative to transesophageal echocardiography, as it allows ruling out the presence of a left atrial appendage thrombus before cardioversion is performed.
      • Pathan F.
      • Hecht H.
      • Narula J.
      • et al.
      Roles of Transesophageal echocardiography and cardiac computed tomography for evaluation of left atrial thrombus and associated pathology: a review and critical analysis.

       Ablation Procedure

      Catheter ablation for AF patients with an ongoing infection is contraindicated; this same criterion applies to COVID-19 patients. Therefore, both AF or AFL ablation procedures should be postponed to optimize antiarrhythmic therapy and control/correct all COVID-19 and non–COVID-19–related modifiable risk factors.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      ,
      • Calkins H.
      • Hindricks G.
      • Cappato R.
      • et al.
      2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus Statement on catheter and Surgical ablation of atrial fibrillation.
      A different scenario is represented by AF/AFL patients showing evidence of tachycardiomyopathy or syncope; in these patients, an early ablation is pivotal to prevent cardiac remodeling and dysfunction and improve outcomes.
      • Della Rocca D.G.
      • Santini L.
      • Forleo G.B.
      • et al.
      Novel perspectives on arrhythmia-Induced cardiomyopathy: pathophysiology, clinical manifestations and an update on invasive management Strategies.
      Also, ablation of drug-refractory AF and AFL with repeated emergency room visits should be performed within less than 3 months.
      The European Society for Cardiology
      ESC Guidance for the Diagnosis and Management of CV Disease during the COVID-19 Pandemic.
      ,
      • Della Rocca D.G.
      • Mohanty S.
      • Mohanty P.
      • et al.
      Long-term outcomes of catheter ablation in patients with longstanding persistent atrial fibrillation lasting less than 2 Years.
      • Della Rocca D.G.
      • Di Biase L.
      • Mohanty S.
      • et al.
      Targeting non-pulmonary vein triggers in persistent atrial fibrillation: results from a prospective, Multicentre, observational Registry.
      • Della Rocca D.G.
      • Tarantino N.
      • Trivedi C.
      • et al.
      Non-pulmonary vein triggers in nonparoxysmal atrial fibrillation: Implications of pathophysiology for catheter ablation.
      Of note, universal testing is of utmost importance to create a safe workplace for patients and health care workers, as asymptomatic carriers can be highly contagious and could be unexpectedly admitted.
      • Mohanty S.
      • Lakkireddy D.
      • Trivedi C.
      • et al.
      Creating a safe workplace by universal testing of SARS-CoV-2 infection in asymptomatic patients and healthcare workers in the electrophysiology units: a Multi-center experience.
      In case of intubation procedure, this needs to be done out of the electrophysiology laboratory to prevent contamination.

       Follow-up in COVID-19 Patients Suffering from Arrhythmias

      The follow-up of patients suffering from arrhythmias must be safe in order to prevent patients from being reinfected by COVID-19. Indeed, as the pandemic progressed, telemedicine has been extensively adopted,
      • Forleo G.B.
      • Tesauro M.
      • Panattoni G.
      • et al.
      Impact of continuous Intracardiac ST-Segment monitoring on Mid-term outcomes of ICD-Implanted patients with coronary artery disease. Early results of a prospective comparison with conventional ICD outcomes.
      ,
      • Della Rocca D.G.
      • Albanese M.
      • Placidi F.
      • et al.
      Feasibility of automated detection of Sleep apnea using Implantable pacemakers and defibrillators: a comparison with Simultaneous polysomnography Recording.
      allowing face-to-face outpatient appointments to be replaced by teleconsultations.
      • Piro A.
      • Magnocavallo M.
      • Della Rocca D.G.
      • et al.
      Management of cardiac Implantable electronic device follow-up in COVID-19 pandemic: lessons learned during Italian lockdown.
      ,
      • Magnocavallo M.
      • Bernardini A.
      • Mariani M.V.
      • et al.
      Home delivery of the communicator for remote monitoring of cardiac Implantable devices: a Multicenter experience during the covid-19 lockdown.
      In the TeleCheck-AF project, telemedicine was implemented with remote monitoring of rhythm and frequency of AF, allowing a complete management of patients, thanks to a mobile phone app using photoplethysmography technology through the built-in camera.
      • Gawałko M.
      • Duncker D.
      • Manninger M.
      • et al.
      The European TeleCheck-AF project on remote app-Based management of atrial fibrillation during the COVID-19 pandemic: centre and patient experiences.
      Probably, this model of outpatient management of arrhythmias, thanks to the new wearable technologies, leading to the reduction of the number of hospital visits and health care costs, will remain even after the pandemic and represent an additional weapon in the diagnosis and management of arrhythmias in the near future.
      • Caillol T.
      • Strik M.
      • Ramirez F.D.
      • et al.
      Accuracy of a Smartwatch-derived ECG for diagnosing Bradyarrhythmias, Tachyarrhythmias, and cardiac ischemia.

      Summary

      Cardiac arrhythmias occur in 6% to 17% of COVID-19 patients. Their prevalence is significantly higher (up to 44%) in patients admitted to intensive care unit, becoming the second most frequent complication after acute respiratory distress syndrome. Supraventricular arrhythmias, mainly AF, are more frequent than ventricular ones. Several mechanisms can contribute to an increased risk of cardiac arrhythmias during COVID-19 infection, ranging from direct myocardial damage to electrolyte imbalance. The main aim of COVID-19–related supraventricular arrhythmia management is to establish a safe treatment plan according to each patient’s overall clinical conditions, keep in mind any possible drug-to-drug interactions, and minimize the risk of exposure for the staff and other non–COVID-19 patients.

      Clinics care points

      • Arrhythmogenesis is correlated to several pathophysiological mechanisms: hypoxia, myocardial ischemia, inflammation, electrolyte and fluid imbalance.
      • Rate Control should be preferred in critically ill COVID-19 patients.- Atrial fibrillation is an indipendent predictor of mortality.
      • COVID-19 patients who experienced atrial fibrillation should be monitored to evaluate the burden of arrhythmia.

      Disclosure

      Dr J.D. Burkhardt is a consultant for Biosense Webster and Stereotaxis. Dr L. Di Biase is a consultant for Biosense Webster, Boston Scientific, Stereotaxis, and St. Jude Medical; and has received speaker honoraria from Medtronic, Atricure, EPiEP, and Biotronik. Dr A. Natale has received speaker honoraria from Boston Scientific, Biosense Webster, St. Jude Medical, Biotronik, and Medtronic; and is a consultant for Biosense Webster, St. Jude Medical, and Janssen. All other authors have reported that they have no relationships relevant to the contents of this article to disclose.

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