Coronaviruses are a strand of viral illnesses that produce respiratory disease. The strand behind COVID-19, which produced a pandemic drawing international attention, differs from the other coronavirus strands. COVID-19 produces acute and severe respiratory syndromes.1 There has been a strong link to patients developing myocarditis following COVD-19 diagnosis. The coronavirus SARS-CoV-2 causes acute and severe respiratory distress in the infected host. The virus attacks angiotensin-converting enzyme II receptors, leading to COVID-connected pneumonia. Insult to the nervous system can result in acute myocardial injury that permanently impairs the cardiovascular system.1
The muscular structure of the heart can become inflamed in a condition known as myocarditis. Myocarditis characteristically results in inflammation of infiltrates and associated myocardial injury. Injury occurs without the presence of an ischemic culprit. Viruses remain the most common reason for myocarditis.2
Myocarditis can range from mild and self-limiting to permanently damaging cardiovascular function. Severe cases may result in sudden cardiomyopathies with hemodynamic collapse or life-threating arrhythmias.3 COVID-19 potentially manifests in acute and chronic myocarditis via different mechanisms that result in a variation of arrhythmias.
Responsible for the regulation of blood pressure and fluid balance within the body, angiotensinogen is part of a hormone system known as the renin-angiotensin system. Angiotensinogen is converted to angiotensin I, which then interacts with angiotensin-converting enzyme. Angiotensin-converting enzyme is formed in the pulmonary epithelium of the lungs and responsible for the conversion of angiotensin I to angiotensin II.
Angiotensin II is the most potent vasoconstrictor our bodies produce.4 In the acute setting, angiotensin-converting enzyme II is considered one of the possible causes of acute myocarditis producing injury to cardiomyocytes due to COVID-19.
The hypothesis is that COVID-19 enters human cells by attaching the spike protein to the angiotensin-converting enzyme II protein membrane, gaining cellular entry.2 Pericardial inflammation due to either edema or effusion may be observed in severe and sudden-onset myocarditis, possibly triggering the manifestation of abrupt arrhythmias. Ischemia to the myocardium potentially results from damage to the cells along the capillary walls of the cardiac microvasculature.2 The inside of the blood vessel wall contains cells that release substances controlling relaxation, contraction, enzymatic control for coagulation, immune function, and platelet binding. Angiotensin II has hypercoagulability correlating with the increased production and discharge of plasminogen activator inhibitor type I from inside the blood vessel wall and cells of smooth muscle that will increase tissue factor expression. Tissue factor expression is also known as the high-affinity receptor, which is the essential substance needed for the activity of factor VII/VIIa.
Tissue factor expression forms a hemostatic barrier on perivascular and epithelial cells on the organ and body surfaces. Tissue factor VIIa is the main receptor responsible for initiating the chain reaction of clotting and is vital for maintaining hemostasis. Platelets have angiotensin II receptors on them, allowing platelet activation and aggregation to occur.4 Cardiac muscle fibers are connected at intercalated discs by gap junctions, allowing the movement of ions and molecules from cell to cell. A direct electrical connection is created here between these muscle fibers, allowing an action potential to travel across an intercalated disk, rapidly moving from one cardiac muscle fiber to another.
Cardiac muscle fibers are connected mechanically, chemically, and electrically to each other, resulting in the appearance of one large muscle fiber. This rationale is why cardiac muscle is described as a functional syncytium. Chronic myocarditis in patients with COVID-19 can potentially be exacerbated by the secondary release of dysfunctional chronic gap junction proteins released by cells interfering with the communication of other cells. Production of arrhythmias is exacerbated when there are inherited tendencies present. Reentry arrhythmias occur due to chronic inflammation or by nonischemic scarred cells on the myocardium.2
Objective clinical signs of heart failure like chest pain, irregular ECGs that can impersonate acute coronary syndrome, and ventricular arrhythmias are common presentations in patients with acute myocarditis.5 The clinical presentation of patients with COVID-related myocarditis can be variable. Some may present with relatively mild symptoms and complaints of fatigue. Even minor cases may display dyspnea, chest pain or pressure, and exertional chest tightness.2 A previous history of cardiovascular disease increases mortality rates in patients with COVID-19.6
Patients with severe cases of COVID-19 related to myocarditis can present with signs of right-sided failure, increased jugular venous pressure, peripheral edema, and right upper quadrant abdominal pain. The most emergent presentations occur within 2–3 weeks of contracting COVID-19, which is sudden- and severe-onset myocarditis, ventricular dysfunction, and heart failure. The early symptoms of this form of myocarditis mimic sepsis with fever, tachyarrhythmias, mottling of extremities, and lower-than-normal pulse pressure.2
ECG readings of patients with myocarditis can show depressed PR- and ST-segment elevation; however, this is typically seen more often in cases of pericarditis. Myocarditis can also present with new-onset bundle branch block, bradycardia, and advanced AV nodal blocks.2
Additionally, ECG monitoring can reveal prolonged QT intervals and myocardial irritability in the form of premature ventricular contractions and coronary vessel spasms severe enough to mimic myocardial infarction, and they can even develop into an acute myocardial infarction.7 Myocardial dysfunctions such as reduction of pumping ability, induction of arrhythmias, and electrical conductivity are all consequences of myocarditis.2 Global inversion of the T-waves on the 12-lead ECG is another typical finding.8
Acute myocarditis producing cardiogenic shock can benefit from positive inotropic pharmacological therapy with medications such as milrinone and dobutamine.3 Dobutamine causes skeletal muscles to vasodilate, dropping their afterload, which is the resistance the right ventricle must overcome to eject blood.
Dobutamine produces an increase in inotropic effects while also providing bronchodilator effects from beta-adrenergic stimulation. Milrinone is utilized in the treatment of heart failure for vasodilation, allowing blood to flow more easily. Milrinone produces inotropic effects, thereby increasing the squeeze of the myocardium.3
An estimated 20% of patients with myocarditis will eventually develop chronic inflammatory dilated cardiomyopathy. Use of immunosuppressive and anti-inflammatory medication, like prednisone, will likely elevate their cardiovascular function.3 Antiviral drugs are utilized in the treatment of patients with COVID-19 but can result in cardiac deficiency and cardiotoxicity.1
COVID-19 has resulted in a global pandemic. As healthcare professionals, we know it as a strand of coronavirus. However, it impacts our patients in more significant ways than past strands. We commonly see the devastating effects of the virus on the respiratory system. Just as devastating and potentially longer lasting are the risks posed to the cardiovascular system. COVID-19’s ability to infect heart tissue, leading to myocarditis, only increases the risk the virus poses.
1. Zheng Y, Ma Y, Zhang J, Xie X. COVID-19 and the cardiovascular system. Nature Reviews Cardiology, 2020; 17: 259–60.
2. Siripanthong B, Nazarian S, Muser D, et al. Recognizing COVID-19–related myocarditis: The possible pathophysiology and proposed guideline for diagnosis and management. Heart Rhythm, 2020 Sep; 17(9): 1,463–71.
3. Tschöpe C, Cooper LT, Torre-Amione G, Van Linthout S. Management of myocarditis-related cardiomyopathy in adults. Circulation Research, 2019; 124(11): 1,568–83.
4. Rice GI, Thomas DA, Grant PJ, Turner AJ, Hooper NM. Evaluation of angiotensin-converting enzyme (ACE), its homologue ACE2 and neprilysin in angiotensin peptide metabolism. Biochemical Journal, 2004; 383(1): 45–51.
5. Alcaide ML, Bisno AL. Pharyngitis and epiglottitis. Infect Dis Clin North Am, 2007 Jun; 21(2): 449–69.
6. Hendren NS, Drazner MH, Bozkurt B, Cooper, Jr. LT. Description and proposed management of the acute COVID-19 cardiovascular syndrome. Circulation, 2020; 141: 1,903–14.
7. Edelson DP, Sasson C, Chan PS, et al.; and the American Heart Association ECC Interim COVID Guidance Authors. Interim guidance for basic and advanced life support in adults, children, and neonates with suspected or confirmed COVID-19. Circulation, 2020; 141: e933–e943.
8. Glancy DL, Rochon BJ, Ilie CC, et al. Global T-wave inversion in a 77-year-old woman. Proc (Bayl Univ Med Cent), 2009 Jan; 22(1): 81–2.
Kory A. Lane, MEd, NRP, CCEMT-P, NCEE, is a paramedic at Cone Health CareLink Mobile Critical Care, Greensboro, N.C.
Roger L. Layell, FP-C, CCP-C, CCEMT-P, NRP, is a flight and critical care paramedic at Wake Forest Baptist Health AirCare in Winston-Salem, N.C. He has 15 years of experience in the field as a paramedic and 10 of critical care experience in the HEMS environment.