key: cord-0741434-ee780qe4 authors: Spencer, Robert; Choi, Nak Hyun; Potter, Keriann; Suh, Sanghee; Fremed, Michael title: COVID-19 and the young heart: what are we missing? date: 2020-09-09 journal: World J Pediatr DOI: 10.1007/s12519-020-00391-z sha: 5ffb51a2b47fd65c1fe55135780b6c351270fca0 doc_id: 741434 cord_uid: ee780qe4 nan COVID-19 develop some form of cardiac injury. The same study revealed that having pre-existing cardiovascular disease is associated with more severe progression of the virus and that patients with cardiac injury had a significantly higher likelihood of death compared to those without cardiac injury (51% versus 5%, respectively) [6] . But in the absence of more data, it is too early to know the long-term sequelae of cardiac injury in adults, or how these statistics translate to a younger population. What is needed are studies detailing the cardiac involvement in COVID-19 in children as well as studies comparing the clinical profiles of children with COVID-19 who do and do not have cardiac injury. Perhaps subtle changes on the electrocardiogram or mild elevations in biochemical cardiac markers, such as high-sensitivity troponin and N-terminal pro-B-type natriuretic peptide, have been missed. Characterizing these patients' echocardiographic findings would be helpful. Researchers also should attempt to clarify the pathogenesis of cardiac dysfunction with COVID-19, which has been theorized to involve direct myocardial involvement mediated by angiotensin-converting enzyme-2, although this has yet to be definitively established [7] . Endomyocardial biopsies may help to elucidate the pathogenesis of cardiac injury caused by the virus. Finally, because the number of children with cardiac manifestations of COVID-19 is likely small at any one institution, it may be beneficial to focus attention on collaborative, multicenter studies. These larger studies are best suited to help determine the most successful treatment options, as well as the longitudinal outcomes for these patients. Aside from the cardiac injury potentially caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the exploratory treatments for the virus can pose serious cardiac risks. Hydroxychloroquine and azithromycin, which have been combined to treat many patients of all ages with the virus, are known to prolong the QTc interval and, in rare cases, to cause torsade de pointes [8] . And despite the widespread use of these medications, studies have not shown a significant association with lower in-hospital mortality [9, 10] . At the time of writing of this article, the arrhythmogenic potential of other investigational agents, such as remdesivir, is unknown [11] . Patients receiving these novel treatments require close rhythm monitoring, but the optimal monitoring algorithm remains unclear. The safe implementation of these treatments begs several questions: (1) How often should these patients have electrocardiograms? (2) Is telemetry sufficient for monitoring QTc intervals? (3) What is the QTc threshold at which a medication should be held or discontinued? The multisystem inflammatory syndrome in children (MIS-C), which appears to be associated with COVID-19 and has clinical features resembling toxic shock syndrome and atypical Kawasaki disease, also warrants further investigation. Reports of children with this syndrome have increased dramatically in recent months, particularly in Europe and in the United States [12] . Myocardial dysfunction, while usually mild, appears to be present in the majority of patients with this syndrome. A recent study involving 35 patients found that 17% of patients have coronary artery dilation [13] . While none of those patients was found to have a coronary artery aneurysm, another case series reported one patient with this syndrome who developed a coronary artery aneurysm [14] . Moreover, our center recently published a case series involving 17 previously healthy children with MIS-C, of which 16 had abnormal electrocardiograms, 6 moderate or severe ventricular dysfunction, and 7 prominent or echogenic coronaries. Of note, one of our patients developed a medium-sized aneurysm (z score, 5.2) of the left anterior descending coronary artery, which resolved on follow-up echocardiogram. All 17 patients were discharged and returned home after a mean of 7 days, with no fatalities [15] . Lastly, information is lacking regarding COVID-19 in patients with complex congenital heart disease (CHD). Adults with complex CHD, particularly those with single ventricle physiology, are predicted to have a higher risk of cardiac sequelae and a worse overall prognosis once infected with COVID-19 [16] . This assumption is made on the basis of their decreased contractile reserve, and further studies are needed to better understand the extent of these patients' risk. Similarly, it would be helpful to know whether patients with complex CHD in the setting of genetic syndromes (e.g., DiGeorge syndrome) or asplenia have particularly poor outcomes due to reduced immunity. Fortunately, the number of patients with complex CHD and COVID-19 remains low at our center, and we continue to advise patients with all forms of CHD to take all possible precautions to minimize potential exposure to the virus. Despite there being more than 10 million confirmed cases worldwide, the novel coronavirus continues to hold unsolved mysteries [17] . Among these mysteries is how COVID-19 affects children's hearts, how children with cardiac manifestations of the virus can be treated safely, and whether children with complex CHD have worse outcomes. Further epidemiological and multicenter studies are needed to help understand the association between COVID-19 and the heart. Until then, we will continue to face difficult questions and frustrating uncertainty. 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Heart Rhythm COVID-19 and Kawasaki disease: finding the signal in the noise Acute heart failure in multisystem inflammatory syndrome in children (MIS-C) in the context of global SARS-CoV-2 pandemic Hyperinflammatory shock in children during COVID-19 pandemic. The Lancet Multisystem inflammatory syndrome related to COVID-19 in previously healthy children and adolescents in New York City The cardiovascular burden of coronavirus disease 2019 (COVID-19) with a focus on congenital heart disease COVID-19 dashboard by the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University (JHU). 2020 We are deeply grateful to Dr. Julie Glickstein for her support and mentorship.