Cardiovascular Disorders and COVID-19

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Mitra Chitsazan, M.D.[2]Mandana Chitsazan, M.D. [3]Turky Alkathery, M.D. [4]

Complications

Heart Failure

Pathophysiology

• Patients with chronic heart failure (HF) may be at higher risk of developing severe COVID-19 infection due to the advanced age and the presence of multiple comorbidities.
• Both de novo acute heart failure and acute decompensation of chronic heart failure can occur in patients with COVID-19.
• Presumed pathophysiologic mechanisms for the development of new or worsening heart failure in patients with COVID-19 include:
  • Acute exacerbation of chronic heart failure
  • Acute myocardial injury (which in turn can be caused by several mechanisms)
  • Stress cardiomyopathy (i.e., Takotsubo cardiomyopathy)
  • Impaired myocardial relaxation resulting in diastolic dysfunction [i.e., Heart failure with preserved ejection fraction (HFpEF)]
  • Right-sided heart failure, secondary to pulmonary hypertension caused by hypoxia and acute respiratory distress syndrome (ARDS)

Symptoms and signs

• Dyspnea: may overlap with dyspnea due to concomitant respiratory involvement and ARDS due to COVID-19 infection
• Lower limb edema
• Orthopnea
• Paroxysmal nocturnal dyspnea
• Confusion and altered mentation
• Cool extremities
• Cyanosis
• Syncope
• Fatigue
• Hemoptysis
• Palpitations
• Weakness
• Wheezing or cardiac asthma
• Distended jugular veins
• Crackles on auscultation

Electrocardiography (ECG)

• There is no specific electrocardiographic sign for acute heart failure in COVID-19 patients.
• The ECG may help in identifying preexisting cardiac abnormalities and precipitating factors such as ischemia, myocarditis, and arrhythmias.
• These ECG findings may include:
  • Low QRS Voltage
  • Left ventricular hypertrophy
  • Left atrial enlargement
  • Left bundle branch block
  • Poor R progression
  • ST-T changes

Chest x-ray (CXR)

• The Chest x-ray may show evidence of:
  • Cardiomegaly
  • Pulmonary congestion
  • Increased pulmonary vascular markings.
• Signs of pulmonary edema may be obscured by underlying respiratory involvement and ARDS due to COVID-19.

Echocardiography

• A complete standard transthoracic (TTE) has not been recommended in COVID-19 patients considering the limited personal protective equipment (PPE) and the risk of exposure of additional health care personnel.
• To deal with limited resources (both personal protective equipment and personnel) and reducing the exposure time of personnel, a focused TTE to find gross abnormalities in cardiac structure/function seems satisfactory.
• In addition, bedside options, which may be performed by the trained personnel who might already be in the room with these patients, might also be considered. These include:
  • Cardiac point-of-care ultrasound (POCUS)
  • Focused cardiac ultrasound study (FoCUS)
  • Critical care echocardiography
• Cardiac ultrasound can help in assessing the following parameters:
  • Left ventricular systolic function (ejection fraction) to distinguish systolic dysfunction with a reduced ejection fraction (<40%) from diastolic dysfunction with a preserved ejection fraction.
  • Left ventricular diastolic function
  • Left ventricular structural abnormalities, including LV size and LV wall thickness
  • Left atrial size
  • Right ventricular size and function
  • Detection and quantification of valvular abnormalities
  • Measurement of systolic pulmonary artery pressure
  • Detection and quantification of pericardial effusion
  • Detection of regional wall motion abnormalities/reduced strain that would suggest an underlying ischemia

Cardiac biomarkers

• Cardiac Troponins:
  • Elevated cardiac troponin levels suggest the presence of myocardial cell injury or death.
  • Cardiac troponin levels may increase in patients with chronic or acute decompensated HF.
• Natriuretic Peptides:
  • Natriuretic peptides (BNP/NT-proBNP) are released from the heart in response to increased myocardial stress and are quantitative markers of increased intracardiac filling pressure.
  • Elevated BNP and NT-proBNP are of both diagnostic and prognostic significance in patients with heart failure.
  • Increased BNP or NT-proBNP levels have been demonstrated in COVID-19 patients.
  • Increased NT-proBNP level was associated with worse clinical outcomes in patients with severe COVID-19.
  • However, increased natriuretic peptide levels are frequently seen among patients with severe inflammatory or respiratory diseases.
  • Therefore, routine measurement of BNP/NT-proBNP has not been recommended in COVID-19 patients, unless there is a high suspicion of HF based on clinical grounds.

Treatment

• Patients with chronic heart failure are recommended to continue their previous guideline-directed medical therapy, including beta-blockers, ACEI or ARB, and mineralocorticoid receptor antagonists.
• Acute heart failure in the setting of COVID-19 is generally treated similarly to acute heart failure in other settings. These may include:
  • Fluid restriction
  • Diuretic therapy
  • Vasopressors and/or inotropes
  • Ventricular assisted devices and extracorporeal membrane oxygenation (ECMO)
• Beta-blockers should not be initiated during the acute stage due to their negative inotropic effects.
• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) should be used with caution in patients with acute heart failure due to their effect on fluid and sodium retention.

Arrhythmias

Pathophysiology:

Respiratory disease is the chief target of Coronavirus disease 2019 (COVID-19). One-third of patients with severe disease also reported other symptoms including arrhythmia. According to a study done in Wuhan, China, 16.7% of hospitalized and 44.4% of ICU patients with COVID-19 had arrhythmias. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes S-spike to bind to angiotensin-converting enzyme 2 (ACE2) receptors to enter the cells. Type 1 and type 2 pneumocytes exhibit ACE 2 receptors in the lung. Studies report that coronary endothelial cells in the heart and intrarenal endothelial cells and renal tubular epithelial cells in the kidney exhibit ACE2. ACE2 is an inverse regulator of the renin-angiotensin system. The interaction between SARS-CoV2 and ACE2 can bring about changes in ACE2 pathways prompting intense injury to the lung, heart, and endothelial cells. Hypoxia and electrolyte abnormalities that are common in the acute phase of severe COVID-19 can potentiate cardiac arrhythmias. Binding of SARS-CoV-2 to ACE2 receptors can result into hypokalemia which causes various types of arrhythmia. Elevated levels of cytokines as a result of the systemic inflammatory response of the severe Coronavirus disease 2019 (COVID-19) can cause injury to multiple organs, including cardiac myocytes. According to the data based on studies on previous Severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) epidemic and the ongoing COVID-19 outbreak, multiple mechanisms have been suggested for cardiac damage.

Signs and Symptoms:

Arrhythmia or conduction system disease is the nonspecific clinical presentation of COVID-19. Patients may be tachycardic (with or without palpitations) in the setting of other COVID-19-related symptoms (eg, fever, shortness of breath, pain, etc).

• Palpitations: According to a study done in Hubei province,palpitations were reported as a presenting symptom by 7.3 percent of patients.
• Prolong QT Interval: According to a multicenter study done in New York that involved 4250 COVID-19 patients, 260 patients (6.1 percent) had corrected QT interval (QTc) >500 milliseconds at the time of admittance. However, in another study that involved 84 patients who got hydroxychloroquine and azithromycin, the baseline QTc interval was 435 milliseconds before receiving these medications.
• Atrial Arrhythmia: According to a study, among 393 patients with COVID-19, atrial arrhythmias were more common among patients requiring invasive mechanical ventilation than noninvasive mechanical ventilation (17.7 versus 1.9 percent)

• Ventricular Arrhythmia: According to a study done in Wuhan, China. among 187 hospitalized patients with COVID-19, 11 patients (5.9 percent) developed ventricular tachyarrhythmias.
• Cardiac Arrest: According to a Lombardia Cardiac Arrest Registry (Lombardia CARe) of the region Lombardia in Italy. Out of 9806 cases of COVID-19, 362 cases of out-of-hospital cardiac arrest were reported during the study time frame in 2020. During a similar period in 2019, 229 cases of out-of-hospital cardiac arrest were reported, which means an increment of 58% was observed in 2020 among COVID-19 patients. According to the records from a tertiary care hospital in Wuhan. Out of 761 patients with severe COVID-19, 151 patients developed in-hospital cardiac arrest. 136 patients received resuscitation. Out of 136 patients, 119 patients had a respiratory cause. 10 patients had a cardiac cause. 7 patients had other causes. Ventricular fibrillation or pulseless ventricular tachycardia was observed in 8 patients (5.9%), Pulseless electrical activity in 6 patients (4.4%), and asystole in 122 COVID-19 patients (89.7%).

Diagnostic Testing:

• ECG: Most patients with the severe COVID-19, and especially patients who receive QT-prolonging medications, should have a baseline electrocardiogram (ECG) performed at the time of admission to the hospital.The best technique to get the QT interval is with a 12-lead electrocardiogram (ECG). However, to scale back exposure to hospital workers, this could not perpetually be possible. A single-lead ECG might underestimate the QT interval, and there ought to be an effort to use a multiple-lead telemetry system to observe the QT interval.
• Transthoracic echocardiography: Transthoracic echocardiography is recommended for an inpatient with heart failure, arrhythmia, ECG changes, or newly diagnosed cardiomegaly on chest x-ray or CT-chest.

Treatment:

• Polymorphic Ventricular Tachycardia (torsades de pointes): All patients with torsades de pointes (TdP) should be determined if they are hemodynamically stable or unstable through immediate evaluation of the symptoms, vital signs, and level of consciousness.
  • Unstable patients: Patients with COVID-19 with sustained torsades de pointes (TdP) usually become hemodynamically unstable, severely symptomatic because of perfusion failure, or pulseless and should be treated according to standard resuscitation algorithms, including cardioversion/defibrillation. Initial treatment with antiarrhythmic medications is not indicated for hemodynamically unstable or pulseless patients except intravenous (IV) magnesium.
  • Stable patients: In a patient with a single episode of TdP, treatment with IV magnesium along with correction of metabolic/electrolyte disturbances or removal of any inciting medications may be sufficient. The patient should be kept under observation until the electrolytes, and the QT interval nearly normalizes. An IV bolus of 2-gram magnesium sulfate is the standard therapy for an adult. This is equivalent to a dose of 8.12 mmol of magnesium. The clinical situation of a patient determines the rate of magnesium infusion. Infusion occurs over one to two minutes in patients with pulseless cardiac arrest. The infusion should occur over 15 minutes in patients without cardiac arrest as a rapid IV bolus of magnesium can result in hypotension and asystole. Some patients are given a continuous bolus of IV magnesium at a rate of 3 to 20 mg/min until the QT interval is below 0.50 seconds.
• Other Cardiac arrhythmia: The treatment for other arrhythmias in COVID-19 patients is the same as in patients with arrhythmias without COVID-19 infection.
  • Supraventricular tachycardia:
    • Narrow-Complex tachycardia:
      • Vagal maneuvers — including a Valsalva maneuver, carotid sinus massage, bearing down, and immersion of the face in ice water.
      • Adenosine terminates nearly all atrioventricular nodal reentrant tachycardias and atrioventricular reciprocating tachycardias as well as up to 80% of atrial tachycardias, by blocking atrioventricular nodal conduction.
      • Electrical cardioversion is used for patients in unstable condition who do not show response to adenosine.
      • Antiarrhythmic drugs such as procainamide and ibutilide are in patients with hemodynamic instability and in those who show no response to electrical cardioversion.

Out-of-hospital cardiac arrest and Sudden Cardiac Death

Pathophysiology

• Drug induced:

Since the COVID-19 pandemic, several pharmacological therapies have been proposed, one of them is of two anti-malarial and antirheumatic drugs called Chloroquine or Hydroxychloroquine. Due to their cost-effectiveness and easy availability, there is a surge in the use of Chloroquine and Hydroxychloroquine, with or without Azithromycin. The clinical trials in order to estimate their efficacy are still in the preliminary stage, however, a notable concern is of their cardiac adverse effects. This includes QT prolongation and Torsade de pointes (TdP) leading to sudden cardiac death. The risk is there when these drugs are prescribed separately, however it increases several folds when these drugs are administered together, especially in patients with underlying hepatic disease or renal failure.

• Genetic susceptibility:

Epidemiological studies have shown that African Americans have higher COVID-19 associated morbidity and mortality as compared to people from other ethnic groups. Recent studies show that this ethnic predilection is due to the genetics factors which contribute to a common ion channel variant p.Ser1103Tyr-SCN5A which confer an increased risk of drug-induced long QT syndrome (DI-LQTS) and drug-induced sudden cardiac death (DI-SCD). p.Ser1103Tyr-SCN5A generates late or persistent sodium current which is further aggravated by hypoxia or respiratory acidosis secondary to lungs involvement in COVID-19. This has and has been linked to an increased risk of ventricular arrhythmia (VA) such as torsade de pointes and sudden cardiac death (SCD) in African Americans.

Signs and symptoms

• Prolonged QT interval (>500ms).
• Torsades de pointes.

Diagnostic testing

• ECG:
  • ECG shows corrected QT interval (QTc) more than 500 ms.
  • A specific type of abnormal heart rhythm torsades de pointes is seen on the ECG.

Spontaneous Coronary Artery Dissection

Pathophysiology

• In patients with an inflammatory overload, a localized inflammation of the coronary adventitia and periadventitial fat can occur. This could lead to the development of sudden coronary artery dissection in a susceptible patient.