Coronavirus and Arrhythmia

Written by W. Michael Kutayli, MD

Since emerging in Wuhan, China late last year, Coronavirus Disease 2019 caused by severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV 2), has taken the world by storm and Nebraska has been no exception.

There have been over 113,029 cases in our state, resulting in the deaths of 905 of our fellow Nebraskans as a direct result of the Coronavirus pandemic.

SARS-CoV 2 wages war on the human body on multiple fronts. Although the syndrome was initially felt to be characterized by acute lung injury, respiratory failure and death, it has become apparent that COVID-19 is also exemplified by exuberant cytokinemia, with subsequent endothelial inflammation, microvascular thrombosis and multi-organ failure. The cardiovascular system is a common battle front of the disease, and Bryan Heart has been fighting it in the trenches.

COVID-19 affects the cardiovascular system in a multitude of ways. Approximately one-fifth to one-third of hospitalized patients with COVID-19 have myocardial injury, defined as the presence of elevated cardiac troponin level on admission, associated with a worse prognosis and an increased risk of mortality. Described mechanisms of myocardial injury in patients with COVID-19 include oxygen supply demand mismatch, direct viral myocardial invasion, inflammation, coronary plaque rupture with acute MI, microvascular thrombosis and adrenergic stress.

SARS CoV2 is a single stranded RNA virus whose outer membrane spike (S) protein binds with high affinity to the angiotensin converting enzyme 2 receptor, thus entering the host cell. The ACE 2 receptor is involved in regulating the renin angiotensin system. ACE 2 is widely expressed in the body, including in the endothelium and smooth muscle of the vasculature, and in the heart.

Cardiac complications of COVID-19 infection include:

• Troponin elevation
• Reduced systolic function
• Cariogenic shock
• Myocarditis
• And arrhythmia, even in patients without pre-existing heart disease.

Arrhythmias are a common manifestation in patients with COVID-19. Clinical case series of hospitalized patients in China demonstrated palpitations as the initial presenting symptom in 7.3%, and cardiac arrhythmias were reported in 16.7%, including 44.4% of ICU patients (Wang). A study of 323 hospitalized patients (Hu) reported arrhythmia to be present in 30% of the full cohort, and 96% in the critically ill subgroup. Malignant arrhythmias (rapid hemodynamically unstable VT >30 seconds or VF) were noted in 5.9% of hospitalized COVID-19 patients in one single center study of 187 patients (Guo).

EKG Findings in SARS-CoV 2

Human data on EKG changes in the setting of SARS CoV 2 infection are limited. Clearly, ST elevation (focal or diffuse) have been associated with poor prognosis (Bangalore). In a study conducted on rabbits infected with rabbit coronavirus, Alexander et al observed sinus tachycardia, reduced R wave voltages, reduced T wave voltages, and QT prolongation. Mobitz II AV block, PVCs, PACs, and RBBB were also noted in some rabbits.  Conduction abnormalities may be explained by the AV nodal edema and small to moderated macrophages found on pathologic evaluation.

Mechanisms Contributing to Arrhythmias

Multiple potential factors influence the occurrence of arrhythmias.

1. Myocardial Injury
   Myocardial injury, sustained in 19.7 to 27.8% of patients (Guo, Shi), increases the incidence of arrhythmias greatly. Malignant arrhythmias occurred in 17.3% and 1.5% of patients with and without myocardial injury, respectively (Bangalore).
   
   
2. Electrical Instability
   A second mechanism for COVID-19 related arrhythmia is electrical instability associated with QT prolongation. This is especially notable as infected patients may be susceptible to hypokalemia or hypomagnesemia from the disease sequelae such as diarrhea or potentially from drug therapies used for treatment that may prolong the QT interval (e.g. hydroxychloroquine, azithromycin, and protease inhibitors like lopinavir and ritonavir).
   
   
3. Hyper Inflammation
   The hyper inflammatory state characterized by COVID-19 may also contribute to arrhythmias via the cytokine effects on the myocardium directly. COVID-19 inflammatory cytokines prolong the ventricular action potential duration by modulating the expression/activity of the cardiomyocyte K+ and Ca++ ion channels. IL-6 inhibits hERG and prolongs ventricular AP duration, and also inhibits cytochrome P450 3A4, and increasing the bioavailability of several QT prolonging medications.
   
   
4. Renal Function
   Worsening renal function and associated electrolyte abnormalities associated with critical illness may contribute to the development of rhythm abnormalities.

Specific Arrhythmias in COVID-19

Arrhythmias are common in the setting of critical illness, and subsequently arrhythmias in critically ill COVID-19 patients are unlikely to be specific to direct cardiac involvement.

As in most patients with acute illness, sinus tachycardia is common in COVID-19. There have been case reports describing the development of transient heart block in critically ill patients. Anecdotally, first, second and third degree AV block have been reported online in professional society chat discussions (communities.hrsonline.org). Whether these transient findings represent direct cardiac involvement and myocarditis, vagotonic response mediated by activated pulmonary stretch receptors in the setting of mechanical ventilation, or myocardial ischemia in the region of the conduction system is not entirely understood.

Monomorphic ventricular tachycardia can occur, especially in patients with previous myocardial scar. In the absence of pre-existing scar, whether ventricular arrhythmias represent primary arrhythmic events responsive to intervention or more likely a reflection of critical illness (metabolic/hemodynamic/hypoxic) changes is unclear.

Finally, atrial fibrillation and flutter have been observed at times as new onset arrhythmias in COVID-19 patients. This may have implications given the prothrombotic environment of COVID-19, which have yet to be illuminated.

We’re Here to Guide You & Your Patients

COVID-19 has several cardiovascular manifestations, including myocarditis, arrhythmia, and conduction abnormalities. Clearly, there is much we have yet to learn, and further research is needed to emerge victorious in our war against this dangerous new pathogen.

Bryan Heart and Bryan Health will continue to serve as a resource to you and your patients during this COVID-19 era. Please contact us at 402-483-3333 if we can be of further assistance. 

Sources:

The Journal of Innovations in Cardiac Rhythm Management, Cardiovascular Considerations in Coronavirus Disease 2019 with a Special Focus on Arrhythmia, Aug. 2020, Vol 11 Issue 8

https://www.innovationsincrm.com/cardiac-rhythm-management/articles-2020/august/1612-cardiovascular-arrhythmia-coronavirus

Journal of the American College of Cardiology, Coronavirus and Cardiovascular Disease, Myocardial Injury, and Arrhythmia: JACC Focus Seminar, J Am Coll Cardiol. 2020 Oct, 76 (17) 2011–2023 https://www.jacc.org/doi/10.1016/j.jacc.2020.08.059