New-onset atrial fibrillation among COVID-19 patients: A narrative review

Table 1 Comparing coronavirus disease 2019-related new-onset atrial fibrillation and persistent atrial fibrillation in terms of etiology, pathophysiology, contributing risk factors, outcome, and management

	COVID-19-related NOAF	Persistent AF
Etiology and pathophysiology	(1) Diminished availability of ACE-2 receptors contributes to myocardial hypertrophy, vasoconstriction, ROS production, oxidative stress, tissue inflammation, and fibrosis, all of which play a role in the development of AF; (2) Endothelial dysfunction leads to increased vascular permeability and leakage culminating in an overproduction of ROS leading to structural and electrical remodeling predisposing to AF; (3) CD147- and myocyte’s sialic acid-spike protein interaction upregulate the expression of several cytokines and ROS that induce extracellular matrix degradation, cardiac remodeling, and fibrosis; (4) Excessive release of proinflammatory cytokines in cytokine storm leads to ROS production, progressive myocardial cell apoptosis or necrosis, which may lead to conduction disturbances leading to AF; (5) Impaired gas exchanges and intrathoracic pressure swings lead to cardiomyocyte injury and increased frequency of premature atrial beats and induce AF; (6) ANS alteration: SNS-mediated calcium influx increases the frequency of delayed afterdepolarization and triggers AP; PNS activation mediated by intrathoracic pressure swing leads to shortening of right atrial ERP, and APD both induce AF; and (7) Sodium and water resorption increases blood pressure and excretion of potassium increase the resting membrane and enhances depolarization predisposing to AF	Steady generation of ROS triggered by sustained high-electrical activity, followed by intracellular Ca2+ overload together with atrial dilatation, mitochondrial ROS and activation of inflammatory and pro-fibrotic pathways progressively alters gene expression clinically relevant sheep model of persistent AF, leading to myocyte hypertrophy, interstitial fibrosis, and ion channel remodeling, all of which would occur relatively slowly but reach critical levels when AF becomes persistent at a median time of about 2 mo: (1) Oxidative stress by ROS released either by NOX2/4 or mitochondria is the first consequence, the persistence of which leads to shortened APD and RF through reducing rapid L-type Ca2+ current and increasing inward rectifier K+ current promoting the formation and stabilization of rotor that world in a vicious cycle to preserve sustained high electrical activity; and (2) Inflammation leads to profibrotic signaling in response to cardiac injury by promoting fibroblast-to-myofibroblast trans-differentiation leading to either through increased expression of TRP channels or miR-21 resulting in structural remodeling by atrial dilation and fibrosis that maintains AF
Risk factors	(1) Older age; (2) A history of myocardial infarction; (3) Renal dysfunction; (4) Raised D-dimer levels; and (5) Hypertension	Risk factors for progression to more persistent forms of AF among patients with paroxysmal AF and varying degrees of CVD per HATCH score is[62]: (1) Heart failure; (2) Older age; (3) Previous transient ischemic attack or stroke; (4) Chronic obstructive pulmonary disease; and (5) Hypertension
Outcomes	Among patients hospitalized with COVID-19 infection, 5.4% could develop NOAF. All-cause mortality rates are 45.2% vs 11.9% and MACE is 23.8% vs 6.5% for patients with vs without NOAF[67]	Among patients with persistent AF all-cause mortality rate is 4.41% and MACE is 5.09%[67]
Treatment	The initial approach is to enhance the treatment of underlying factors. Hemodynamic instability warrants immediate cardioversion, provided that the risk of embolism is low	Hemodynamic instability warrants immediate cardioversion provided that the risk of embolism is low[15]
	Rate control therapy is preferred over rhythm control unless hemodynamic instability warrants the addition of rhythm control e.g., with amiodarone	A similar efficacy of rate vs rhythm control in all-cause mortality and MACE had been noted. Thus, current guidelines recommend an individualized decision taking into consideration that a rhythm control is most likely to fail in patients with long-term persistent AF (> 1 yr), in whom atrial substrate alteration is greatest
	Anticoagulation: Unfractionated heparin, LMWH is safe to use. Use DOACs with caution as interact with some antiviral medications. VKAs induce a state of vitamin K deficiency that could potentially influence susceptibility to contracting COVID-19	The choice of anticoagulation should be individualized based on the patient’s comorbidities, like other indications for anticoagulation and renal function

COVID-19: Coronavirus disease 2019; ECM: Extracellular matrix; NOAF: New-onset atrial fibrillation; AF: Atrial fibrillation; ROS: Reactive oxygen species; ACE2: Angiotensin-converting enzyme-2; SNS: Sympathetic nervous system; AP: Action potential; PNS: Peripheral nervous system; ERP: Effective refractory period; APD: Action potential duration; TRP: Transient receptor potential; CVD: Cardiovascular disease; MACE: Major adverse cardiovascular events; LMWH: Low molecular weight heparin; DOAC: Direct oral anticoagulant; VKA: Vitamin K antagonist; ANS: Autonomic nervous system.