Cardiac Workup and Monitoring in Hospitalized Children with COVID-19

Abstract

Over 1 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019. This has disproportionately impacted adults, but many children have been infected and hospitalized as well; to date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here we share the approach to the cardiac workup and monitoring utilized at a large congenital heart center in New York City, the epicenter of the COVID-19 pandemic in the United States.

SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19), has infected millions of individuals worldwide with over 1 million infections in the United States at the time of publication.¹ A growing body of literature has described cardiac manifestations of this disease in adults, including myocarditis and arrhythmias,^2,3 electrocardiographic changes including ST segment elevations, T wave inversions, and laboratory abnormalities such as elevated high sensitivity troponin T and N-terminal pro-brain-type natriuretic peptide. Although the pathophysiology is unclear, these abnormalities are associated with increased morbidity, such as need for intubation, and mortality.^4–8 Adults have been disproportionately affected, with children making up under 2% of the infected population.,⁹ Given the smaller numbers of pediatric cases there is a paucity of cardiac data available, making optimal workup and monitoring of these patients uncertain. Recently, groups have reported children with COVID-19, or exposure to close contacts with COVID-19, who develop a multi-system inflammatory syndrome.^10,11 Our institution is currently developing a separate multidisciplinary protocol detailing our approach to these patients.

While recommendations have been published with regards to general pediatrics,¹² pediatric cardiac catheterization,¹³ cardiothoracic surgery,¹⁴ and pulmonary hypertension,^15,16 there remains a lack of consensus guidelines for non-interventional cardiac workup and monitoring of children hospitalized with COVID-19. In this report, we share our approach to the cardiac workup and monitoring of these children with regards to laboratory, electrocardiographic, and imaging evaluation of pediatric patients with COVID-19, with a focus on minimizing staff exposure in the setting of widespread infection. This is based on consensus from a major congenital heart center in New York City, the epicenter of the COVID-19 pandemic in the United States. It was informed by our experience caring for pediatric and adult patients during the pandemic, during which all pediatric admissions to the NewYork-Presbyterian Hospital system were consolidated at Morgan Stanley Children’s Hospital.

Criteria for admission at our institution include, but are not limited to, respiratory distress, supplemental oxygen requirement, cardiovascular instability, dehydration or medications requiring inpatient monitoring. In deciding the appropriate workup, we consider suspicion for cardiac involvement and acuity level (Table).

Table 1.

Cardiac workup and monitoring in children with and without suspicion for cardiac disease

Children WITHOUT Suspicion for Cardiac Disease

Children WITH Suspicion for Cardiac Disease

Baseline labs- as per institution protocol CBC with differential Chemistry ESR/CRP Ferritin Procalcitonin D-dimer Fibrinogen LDH IL-6 Additional Cardiac Screening hs-Troponin, once NT-proBNP, once 15 lead ECG IF: Starting potentially QTc prolonging medication Admitting to ICU Routine echocardiogram- not recommended

Baseline Labs Plus: hs-Troponin T q24–72h NT-proBNP q24–72h Cardiac Monitoring- assess arrhythmia burden 15 Lead ECG- assess for: Myocarditis Rhythm disturbance Baseline QTc, T waves and ST segments Echocardiogram- at discretion of cardiologist including: Ventricular function Valvar regurgitation Pericardial effusion Proximal coronary arteries Additional views if high suspicion of structural or congenital heart disease

CBC= complete blood count; ESR= erythrocyte sedimentation rate; CRP= C-reactive protein; LDH= lactate dehydrogenase; IL-6= interleukin 6; hs-Troponin T = high sensitivity troponin T; NT-proBNP= N-terminal pro-brain-type natriuretic peptide.

I: Children without Suspicion for Cardiac Involvement:

Patients with normal blood pressure and cardiac exam, absence of hepatosplenomegaly, normal cardiac size on chest X-ray, and normal high-sensitivity Troponin T and N-terminal pro-brain-type natriuretic peptide should not raise suspicion for cardiac involvement. All children with confirmed or suspected COVID-19 should have basic laboratory studies drawn according to their institution specific protocol, but should include at least a complete blood count with differential, electrolytes, renal and liver function tests, erythrocyte sedimentation rate and c-reactive protein. In addition, a screening high sensitivity Troponin T and N-terminal pro-brain-type natriuretic peptide should be measured in all admitted children. A chest X-ray is useful in assessing cardiac size, confirming clinically suspected pneumonia, and evaluating respiratory failure and should be obtained for children admitted with COVID-19.

We do not obtain routine electrocardiograms or echocardiograms for children with COVID-19 without suspicion for cardiac disease given the added exposure to staff. However, an electrocardiogram should be obtained for patients requiring ICU admission, as well as prior to starting therapy with QTc prolonging medications, such as hydroxychloroquine, azithromycin and lopinavir/ritonavir,¹⁷ regardless of suspicion for cardiac involvement. Because the QTc interval appears to achieve peak prolongation between day 3 and 4 of treatment¹⁸ and hydroxychloroquine has a long half-life,¹⁹ these patients should continue to have their QTc interval monitored after completing the medication course.

Recently published recommendations suggest that for patients with baseline QRS <120 ms, therapy with hydroxychloroquine ± azithromycin may be initiated when QTc <500. If the QTc is borderline (460–500 ms), treatment may be initiated with caution. For those with baseline QRS ≥120 ms, therapy may be initiated if the QTc <520 ms.^18,20

More frequent monitoring of the QTc interval may be warranted in patients with comorbid conditions known to prolong the QTc, including congenital Long QT Syndrome, severe renal insufficiency²¹, treatment with other QTc prolonging medications, and electrolyte disturbances such as hypokalemia, hypomagnesemia, and hypocalcemia. Electrolyte abnormalities should be corrected prior to initiating QTc prolonging therapies and electrolytes should be closely monitored for the duration of therapy. Concurrent use of other QTc prolonging medications should be avoided.

II: Children with Suspicion or at Risk for Cardiac Involvement

Growing evidence suggests common involvement of multiple organ systems including the heart, kidneys and brain.^22–25 There are many situations for which the pediatric cardiology team might be consulted. These may include abnormal physical exam findings suggestive of heart failure, including inappropriate tachycardia or arrhythmia, gallop, pericardial friction rub, jugular venous distention, evidence of cardiogenic shock, or pulmonary hypertension. Elevated high-sensitivity Troponin T or N-terminal pro-brain-type natriuretic peptide or cardiomegaly on chest X-ray also warrant a cardiology consult. Finally, pediatric cardiology may be consulted for abnormal electrocardiogram, including changes associated with myopericarditis.

Patients who are at risk for severe infection and may be more likely to require admission to the ICU include infants and those with underlying comorbidities such as lung disease, cardiovascular disease, chronic kidney disease, diabetes and metabolic or immune disorders.^26,27 Special consideration should be given to patients with pulmonary hypertension, unrepaired complex congenital heart disease, cyanotic heart disease with oxygen saturations < 85%, ventricular dysfunction requiring medical therapy, and history of heart transplantation on immunosuppressive medications. Due to their higher risk profile, these patients may warrant a more complete evaluation (Table I) than those without preexisting conditions.

Laboratory Studies:

In accordance with our institutional COVID-19 protocol, children with confirmed or suspected COVID-19 requiring admission should undergo laboratory workup including high-sensitivity-Troponin T and NT-proBNP. For children with suspected cardiac involvement, hs-Troponin T and NT-proBNP should be sent every 24–72 hours.

Electrocardiography/Reviewable Cardiac Monitoring

Children with suspicion for cardiac involvement should have a screening ECG to assess for myocarditis or arrhythmia and establish a baseline for QTc intervals, T waves, and ST segments. If the electrocardiogram has findings suggestive of ischemia or inflammation, such as T wave inversions or ST segment elevations or depressions, the electrocardiogram should be repeated daily until the abnormalities resolve or the clinical situation has improved. All patients with suspicion for cardiac involvement, as well as those admitted to the ICU, should be placed on reviewable cardiac monitoring to assess arrhythmia burden.

Echocardiography

The decision to perform an echocardiogram should be made at the discretion of the pediatric cardiologist based on clinical, laboratory and electrocardiographic data, with careful consideration given to reducing viral exposure for staff. At our institution, we developed a protocol for focused studies, keeping the following goals in mind: 1- Assess for signs of myocarditis or myocardial dysfunction, 2- Evaluate for evidence of pulmonary hypertension/pulmonary embolus 3- Minimize exposure to the sonographer. Our current protocol includes assessment of ventricular function, valvar regurgitation, presence of pericardial effusion and, with the newly described multi-system inflammatory syndrome in children^10,11 in mind, evaluation of the proximal coronary arteries in pediatric patients with confirmed or suspected COVID-19 who require an echocardiogram. Children with known or suspected congenital heart disease should have a complete congenital transthoracic echocardiogram when necessary. All measurements should be done after the sonographer has left the patient room.

A complete echocardiogram should likely be obtained in the outpatient setting following discharge. The optimal timing has yet to be established and should be determined while considering clinical evolution, staff exposure, and facility capacity in the setting of the evolving pandemic.

Arrhythmia

Arrhythmia has been reported as a significant issue in adult patients with COVID-19^2,3 and may be secondary to myocardial injury or direct effects of cytokines on sodium and potassium channels.²⁸ Interleukin-6 has been shown to be elevated in those with myocardial injury as compared to those without.²⁹ These same cytokines may also inhibit enzymes required for clearing certain QTc prolonging medications, thereby enhancing their impact on the QTc interva²⁸ Other potential etiologies for arrhythmia include metabolic disturbance³⁰, hypoxia³¹, and genetic dysrhythmias, which may be revealed by acute illness or significant stressors, such as Brugada syndrome³² and Long QT Syndromes.³³ If there is an associated elevation in high sensitivity-Troponin T, early myocarditis should be considered.³⁴ Due to the risk of arrhythmia, these patients should be placed on reviewable cardiac monitoring.

Limitations:

Significant limitations exist that may impact the relevance of this approach. The number of pediatric patients with COVID-19 is small relative to the number of adults, therefore, the data it is based on is largely from adult populations. Furthermore, the natural history and underlying pathophysiology of this disease in children, including the newly emerging multi-system inflammatory syndrome in children, is just now being described. Additionally, prospective data collection is necessarily impeded by the need to minimize exposure of phlebotomy, ECG, and echocardiogram staff. These practices reflect our best understanding at the time of writing; however, our knowledge of this disease and its various presentations is constantly evolving and clinical practice must necessarily evolve in-kind.

Conclusion:

Pediatric patients with COVID-19 infection may require cardiology consultation for a variety of indications. The extent of workup and monitoring of these patients should be based on careful determination of clinical suspicion for cardiac disease and level of acuity of each patient, as well as the expected impact the information will have on clinical management. As the full picture of the multi-system inflammatory syndrome in children emerges, the role of the pediatric cardiologist will likely evolve further. More information obtained from multi-center collaboration is needed to establish definitive guidelines.