This research topic highlights quality case reports from our pediatric cardiology section, including articles submitted to both Frontiers in Pediatrics and Frontiers in Cardiovascular Medicine, demonstrating the interdisciplinary nature of Frontiers' journals sections. Case reports aim to highlight unique cases of patients that present with an unexpected/unusual diagnosis, treatment outcome, or clinical course.?Case reports provide insight into the differential diagnosis, decision making, and clinical management of unusual cases and are a valuable educational tool.

University Medical Center Schleswig-Holstein

Exploring Clinical Cases in the Field of Pediatric Cardiology for 2021

. This research topic covers a range of life-threatening conditions in children, including hypertrophic cardiomyopathy, LQT3 syndrome, iliac vein compression syndrome, Kingella kingae, SARS-CoV-2 infection, pericarditis and hypothyroidism. <ul> <li>Hypertrophic cardiomyopathy can be prevented with early implantable cardioverter-defibrillator placement if two or more clinical risk factors are present.</li> <li>Mexiletine can be used to treat high-risk LQT3 patients in the neonatal period in addition to b-blocker therapy.</li> <li>Iliac Vein Compression Syndrome can be diagnosed through imaging and angiography, and may require stent placement in the future.</li> <li>Kingella kingae can cause fulminant infective endocarditis and emergency venoarterial extracorporeal membrane.</li> <li>SARS-CoV-2 infection can cause acute intracardiac thrombosis, which can be successfully resected via cardiac surgery.</li> <li>Pericarditis can be difficult to diagnose, but can be successfully treated with oral prednisone.</li> <li>Hypothyroidism can lead to serious cardiovascular manifestations if not diagnosed in time, and can be improved rapidly with levothyroxine supplementation.</li> </ul>

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Frontiers in Cardiovascular Medicine

Pediatric Cardiology

Frontiers in Pediatrics

Case Reports in Pediatric Cardiology: 2021

Case reports are of great interest for clinicians in the field of Pediatric Cardiology. One of the reasons is the rarity of many cardiac conditions in children that do not allow studies with large number of patients. In addition, the clinical information and experience in case reports might help treating other pediatric patients in future.A good case report carries this information in that way that readers can learn from it and ideally learning points are provided. In this Research Topic selected pediatric case reports published in 2021 are presented and illustrate that case reports particularly contribute to the management of rare diseases. This is nicely demonstrated by <a href="https://doi.org/10.3389/fped.2021.694782">Ji et al.</a> who report a case of May-Thurner syndrome in a pediatric patient. A syndrome that normally and typically affects women in their third to fifth decade of life (<a href="#B1">1</a>, <a href="#B2">2</a>). Apart from describing the diagnostic methods, the authors also discuss potential treatment options. However, case reports are particularly useful if they cover cutting-edge topics such as this was shown by <a href="https://doi.org/10.3389/fped.2021.656720">Bigdelian et al.</a> They present a case series (three cases) of patients with COVID-19 infection and an intracardiac thrombosis that was successfully treated by cardiac surgery. Although, children are known to be typically less affected by COVID-19, this report demonstrated that physicians should also be aware of a potential hypercoagulopathy in young patients. That we also must think about other causes than COVID-19 when children present with fever at the present time, is nicely described by <a href="https://doi.org/10.3389/fped.2021.694678">Lubocka and Sabiniewicz</a> who present a child with fibrinous pericarditis. The various infective and non-infective etiologies of pericarditis are discussed by the authors, and treatment strategies are presented. In the patient described a chest trauma was considered as a possible reason for the pericarditis. Sometimes, other diseases can mimic cardiac inflammation, and this was shown by <a href="https://doi.org/10.3389/fcvm.2021.698089">Zhang et al.</a> who report a 6-year-old boy with frequent convulsions and loss of consciousness who was initially diagnosed with fulminant myocarditis. Electrocardiogram at presentation showed a third-degree atrioventricular block and echocardiography diagnosed an enlarged left ventricle. The child was also found to have a developmental delay. A review of the patients' history finally brought clarity about the diagnosis. The patient suffered from hypothyroidism and in the discussion the effects of hypothyroidism on the cardiovascular system are described (<a href="https://doi.org/10.3389/fcvm.2021.698089">Zhang et al.</a>). Infective endocarditis is another rare condition in children, especially if they do not suffer from congenital heart disease. The case report by <a href="https://doi.org/10.3389/fped.2021.707760">Joye et al.</a> is presenting a 6-year-old girl with infective endocarditis due to an infection with Kingella kingae. Rapid cardiac deterioration required emergency venoarterial extracorporeal membrane oxygenation (<a href="https://doi.org/10.3389/fped.2021.707760">Joye et al.</a>). Beside vegetations at the aortic valve level, a para-aortic abscess was diagnosed, and the patient underwent surgical treatment. A second surgery was necessary 3 months later due to a para-aortic pseudoaneurysm with good results. The authors discuss the literature about K. kingae infective endocarditis and their treatment strategy.Increasing interest is paid to inherited cardiac conditions in pediatric patients. In this Research Topic two final articles cover this aspect and show the importance of genetic testing (<a href="https://doi.org/10.3389/fped.2021.674041">Bagkaki et al.</a>; <a href="https://doi.org/10.3389/fcvm.2021.810291">Li et al.</a>). <a href="https://doi.org/10.3389/fped.2021.674041">Bagkaki et al.</a> report about a family with long QT type 3 due to a missense mutation in the SCN5A gene. They show that the index patient, a neonate, was successfully treated with an oral medication of propranolol and mexiletine. Mexiletine was able to normalize the prolonged QTc at low therapeutic serum levels (<a href="https://doi.org/10.3389/fped.2021.674041">Bagkaki et al.</a>). In the discussion section, the effects of mexiletine and the challenge of mexiletine treatment in very young children are discussed (<a href="https://doi.org/10.3389/fped.2021.674041">Bagkaki et al.</a>). The second case report by <a href="https://doi.org/10.3389/fcvm.2021.810291">Li et al.</a> describes a 7-year-old girl with hypertrophic cardiomyopathy and previous history of recurrent cardiac arrests. Whole exome sequencing was performed showing a de novo c.2723T&gt;C (p.L908P) heterozygous mutation in the MYH7 gene. The patient underwent implantation of an implantable cardioverter defibrillator and received antiarrhythmic and heart failure treatment (<a href="https://doi.org/10.3389/fcvm.2021.810291">Li et al.</a>).Each article of the presented selection of case reports fulfills the criteria of a &#x201c;good case report.&#x201d; The reports often go beyond describing and discussing the particular case but even discuss the presented topic in detail and hereby provide a mini review.The collection also shows the increasing knowledge in pediatric cardiology and encourages other colleagues for presenting their interesting cases and for performing research studies on rare pediatric cardiac diseases.The author confirms being the sole contributor of this work and has approved it for publication.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Editorial: Case Reports in Pediatric Cardiology: 2021

Background: Hypertrophic cardiomyopathy (HCM) is the second most common cardiomyopathy in childhood with a life-threatening risk. Implantable cardioverter-defibrillator (ICD) placement is recommended for early prevention if there are two or more clinical risk factors. Pediatric patients with HCM are at a higher risk of sudden cardiac death (SCD), but there are limited reports on indications for ICD implantation in children. Herein we describe the case of Myh7 mutation-induced HCM and cardiac arrest in a patient and evaluated information originating from genetic background to guide ICD administration.Case Presentation: The patient was a girl aged 7 years and 8 months who had been diagnosed with cardiomyopathy in utero 8 years prior. She had had recurrent cardiac arrests within the last 4 years. Electrocardiography indicated abnormalities in conduction, and ST segment changes. Echocardiography indicated significant left ventricular hypertrophy and hypertrophic systolic interventricular septum. Cardiac magnetic resonance imaging depicted general heart enlargement with hypertrophy, and delayed enhancement in myocardium with perfusion defect was also evident. Whole exon sequencing identified a de novo c.2723T>C (p.L908P) heterozygous mutation in the MYH7 gene. MYH7 p.L908P predicted unstable protein structure and impaired function. The patient was scheduled for ICD implantation. There were no complications after ICD implantation, and she was discharged from hospital on the 10th day. Regular oral beta-blockers, amiodarone, spironolactone, and enalapril were administered, and she was required to attend hospital regularly for follow-up. During follow-up there were no cardiac arrests. Literature review of clinical prognoses associated with genetic mutations of MYH7, MYBPC3, TNNI3, TNNT2, and TPM1 in pediatric HCM patients with and without ICD implantation indicated that they were totally differently. Previous reports also indicated that gene mutations predicted earlier onset of cardiac hypertrophy, and increase likelihood of SCD.Conclusion: Variant burden and variant type contribute to the risk of adverse events in pediatric HCM. Early recognition and intervention are vital in children. Gene mutation could be considered an indication for early ICD placement during standard risk stratification of HCM patients. Whether this extends to the majority of pediatric patients requires further investigation.

Background: Hypertrophic cardiomyopathy (HCM) is the second most common cardiomyopathy in childhood with a life-threatening risk. Implantable cardioverter-defibrillator (ICD) placement is recommended for early prevention if there are two or more clinical risk factors. Pediatric patients with HCM are at a higher risk of sudden cardiac death (SCD), but there are limited reports on indications for ICD implantation in children. Herein we describe the case of Myh7 mutation-induced HCM and cardiac arrest in a patient and evaluated information originating from genetic background to guide ICD administration.Case Presentation: The patient was a girl aged 7 years and 8 months who had been diagnosed with cardiomyopathy in utero 8 years prior. She had had recurrent cardiac arrests within the last 4 years. Electrocardiography indicated abnormalities in conduction, and ST segment changes. Echocardiography indicated significant left ventricular hypertrophy and hypertrophic systolic interventricular septum. Cardiac magnetic resonance imaging depicted general heart enlargement with hypertrophy, and delayed enhancement in myocardium with perfusion defect was also evident. Whole exon sequencing identified a de novo c.2723T&gt;C (p.L908P) heterozygous mutation in the MYH7 gene. MYH7 p.L908P predicted unstable protein structure and impaired function. The patient was scheduled for ICD implantation. There were no complications after ICD implantation, and she was discharged from hospital on the 10th day. Regular oral beta-blockers, amiodarone, spironolactone, and enalapril were administered, and she was required to attend hospital regularly for follow-up. During follow-up there were no cardiac arrests. Literature review of clinical prognoses associated with genetic mutations of MYH7, MYBPC3, TNNI3, TNNT2, and TPM1 in pediatric HCM patients with and without ICD implantation indicated that they were totally differently. Previous reports also indicated that gene mutations predicted earlier onset of cardiac hypertrophy, and increase likelihood of SCD.Conclusion: Variant burden and variant type contribute to the risk of adverse events in pediatric HCM. Early recognition and intervention are vital in children. Gene mutation could be considered an indication for early ICD placement during standard risk stratification of HCM patients. Whether this extends to the majority of pediatric patients requires further investigation.

Genetic Clues on Implantable Cardioverter-Defibrillator Placement in Young-Age Hypertrophic Cardiomyopathy: A Case Report of Novel MYH7 Mutation and Literature Review

Background: Early diagnosis of long QT type 3 (LQT3) syndrome during the neonatal period is of paramount clinical importance. LQT3 syndrome results in increased mortality and a mutation-specific response to treatment compared to other more common types of LQT syndrome. Mexiletine, a sodium channel blocker, demonstrates a mutation-specific QTc shortening effect in LQT3 syndrome patients.Case Presentation: A neonate manifested marked QTc prolongation after birth. An electrocardiogram (ECG) recording was performed due to positive family history of genetically confirmed LQT3 syndrome (SCN5A gene missense mutation Tyr1795Cys), and an association with sudden cardiac death was found in family members. The mexiletine QTc normalizing effect (QTc shortening from 537 to 443 ms), practical issues related to oral mexiletine treatment of our young patient, along with a literature review regarding identification and mexiletine treatment in infants with LQT3 syndrome are presented.Conclusions: Mexiletine could be considered in the treatment of high-risk LQT3 patients already in the neonatal period in addition to b-blocker therapy. Availability of standardized commercial mexiletine pediatric formulas, serum mexiletine level analyses, and future prospective studies are needed to evaluate the potential beneficial effect of early mexiletine treatment on the incidence of future acute cardiac events in these high-risk LQT syndrome patients.

Background: Early diagnosis of long QT type 3 (LQT3) syndrome during the neonatal period is of paramount clinical importance. LQT3 syndrome results in increased mortality and a mutation-specific response to treatment compared to other more common types of LQT syndrome. Mexiletine, a sodium channel blocker, demonstrates a mutation-specific QTc shortening effect in LQT3 syndrome patients.Case Presentation: A neonate manifested marked QTc prolongation after birth. An electrocardiogram (ECG) recording was performed due to positive family history of genetically confirmed LQT3 syndrome (SCN5A gene missense mutation Tyr1795Cys), and an association with sudden cardiac death was found in family members. The mexiletine QTc normalizing effect (QTc shortening from 537 to 443 ms), practical issues related to oral mexiletine treatment of our young patient, along with a literature review regarding identification and mexiletine treatment in infants with LQT3 syndrome are presented.Conclusions: Mexiletine could be considered in the treatment of high-risk LQT3 patients already in the neonatal period in addition to b-blocker therapy. Availability of standardized commercial mexiletine pediatric formulas, serum mexiletine level analyses, and future prospective studies are needed to evaluate the potential beneficial effect of early mexiletine treatment on the incidence of future acute cardiac events in these high-risk LQT syndrome patients.

Mexiletine Treatment for Neonatal LQT3 Syndrome: Case Report and Literature Review

Iliac vein compression syndrome (IVCS) or May–Thurner syndrome occurs predominantly in young to middle-aged women. Here we reported a case of IVCS in a 5-year-old boy. The child was admitted to our vasculocardiology department with left lower extremity that had been swollen for 1 month. Blood tests revealed coagulation routine and platelets in the normal ranges. Computer tomography angiography (CTA) and magnetic resonance imaging (MRI) showed the left common iliac vein had become narrow before it entered the right common iliac vein. To further clarify, we performed angiography, which clearly showed the stenosis and the blood return of the left common iliac vein. So IVCS was diagnosed. What is more, we found the aorta descended to the right of the spine, and this may be the reason for the apparent compression of the left common iliac vein. Given the young age and mild symptoms of the child, the treatment was conservative mainly including elevation of the affected limb, wearing medical elastic socks, and short-term oral aspirin for anticoagulation. Meanwhile, the boy is being followed up closely. If the swelling of the left lower extremity significantly increases, stent placement may need to be considered in the future.

Iliac vein compression syndrome (IVCS) or May&#x2013;Thurner syndrome occurs predominantly in young to middle-aged women. Here we reported a case of IVCS in a 5-year-old boy. The child was admitted to our vasculocardiology department with left lower extremity that had been swollen for 1 month. Blood tests revealed coagulation routine and platelets in the normal ranges. Computer tomography angiography (CTA) and magnetic resonance imaging (MRI) showed the left common iliac vein had become narrow before it entered the right common iliac vein. To further clarify, we performed angiography, which clearly showed the stenosis and the blood return of the left common iliac vein. So IVCS was diagnosed. What is more, we found the aorta descended to the right of the spine, and this may be the reason for the apparent compression of the left common iliac vein. Given the young age and mild symptoms of the child, the treatment was conservative mainly including elevation of the affected limb, wearing medical elastic socks, and short-term oral aspirin for anticoagulation. Meanwhile, the boy is being followed up closely. If the swelling of the left lower extremity significantly increases, stent placement may need to be considered in the future.

Case Report: Rare Iliac Vein Compression (May–Thurner) Syndrome in a Pediatric Patient

Kingella kingae is a gram-negative coccobacillus belonging to the HACEK group (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) and is a common oropharyngeal colonizer of healthy young children. Osteoarticular infection is the most commonly reported invasive Kingella kingae infection in children, usually presenting a mild clinical picture. However, it can also cause severe invasive infections, especially infective endocarditis, with a high complication rate. We report the case of a 6-year-old girl, with no past medical history, who presented with fulminant infective endocarditis due to Kingella kingae. She received emergency venoarterial extracorporeal membrane oxygenation support, rapidly underwent cardiac surgery, and was then treated using ceftriaxone for 4 weeks as recommended by the American Heart Association. The patient's postoperative course was marked by a cerebral ischemic stroke consistent with septic embolism. She also presented with a para-aortic pseudoaneurysm that required a secondary surgical procedure, with a good postoperative result. This report illustrates a case of fulminant infective endocarditis due to Kingella kingae and responsible for two major complications. We also describe the preventive valve surgery performed to ensure the preservation of valve function and its capacity for growth.

Kingella kingae is a gram-negative coccobacillus belonging to the HACEK group (Haemophilus species, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, and Kingella species) and is a common oropharyngeal colonizer of healthy young children. Osteoarticular infection is the most commonly reported invasive Kingella kingae infection in children, usually presenting a mild clinical picture. However, it can also cause severe invasive infections, especially infective endocarditis, with a high complication rate. We report the case of a 6-year-old girl, with no past medical history, who presented with fulminant infective endocarditis due to Kingella kingae. She received emergency venoarterial extracorporeal membrane oxygenation support, rapidly underwent cardiac surgery, and was then treated using ceftriaxone for 4 weeks as recommended by the American Heart Association. The patient's postoperative course was marked by a cerebral ischemic stroke consistent with septic embolism. She also presented with a para-aortic pseudoaneurysm that required a secondary surgical procedure, with a good postoperative result. This report illustrates a case of fulminant infective endocarditis due to Kingella kingae and responsible for two major complications. We also describe the preventive valve surgery performed to ensure the preservation of valve function and its capacity for growth.

Fulminant Infective Endocarditis Due to Kingella Kingae and Several Complications in a 6-Year-Old Girl: A Case Report

We herein describe a case series of children with SARS-CoV-2 infection (COVID-19) complicated with acute intracardiac thrombosis. The diagnosis of COVID-19 was confirmed through the reverse transcription-polymerase chain reaction (RT-PCR). Transthoracic echocardiography of patients revealed large intracardiac mobile masses resected successfully via cardiac surgery. The underlying mechanisms of this thrombus in the COVID-19 infection may be attributed to the hypercoagulation and inflammatory state of the disease incurred by the SARS-CoV-2 virus.

We herein describe a case series of children with SARS-CoV-2 infection (COVID-19) complicated with acute intracardiac thrombosis. The diagnosis of COVID-19 was confirmed through the reverse transcription-polymerase chain reaction (RT-PCR). Transthoracic echocardiography of patients revealed large intracardiac mobile masses resected successfully via cardiac surgery. The underlying mechanisms of this thrombus in the COVID-19 infection may be attributed to the hypercoagulation and inflammatory state of the disease incurred by the SARS-CoV-2 virus.

Case Report: Acute Intracardiac Thrombosis in Children With Coronavirus Disease 2019 (COVID-19)

Pericarditis is a rare, but severe cause of chest pain in children that can easily be overlooked during routine diagnostics. Fibrinous pericarditis was recognized in a 5-year old patient who presented with fever and chest pain. Despite thorough diagnostics, no evident etiological factor was found. Furthermore, the disease was unresponsive to broad-spectrum antibiotics and NSAIDs, however oral prednisone was found to cause rapid improvement in the patients' condition. It was presumed that the patient's condition was caused by a blunt trauma to the chest experienced 3 days prior to the onset of symptoms. In an 8-month follow-up the patient remains in good overall condition and no recurrences were observed.

Pericarditis is a rare, but severe cause of chest pain in children that can easily be overlooked during routine diagnostics. Fibrinous pericarditis was recognized in a 5-year old patient who presented with fever and chest pain. Despite thorough diagnostics, no evident etiological factor was found. Furthermore, the disease was unresponsive to broad-spectrum antibiotics and NSAIDs, however oral prednisone was found to cause rapid improvement in the patients&apos; condition. It was presumed that the patient&apos;s condition was caused by a blunt trauma to the chest experienced 3 days prior to the onset of symptoms. In an 8-month follow-up the patient remains in good overall condition and no recurrences were observed.

Case Report: Unexplained Fever and Chest Pain in a 5-Year-Old

Background: Hypothyroidism can lead to bradycardia, reduced cardiac output, cardiac enlargement, and abnormal electrocardiogram. However, hemodynamic instability and malignant arrhythmias due to hypothyroidism is rarely reported in children.Patient Findings: We report the case of a child with third-degree atrioventricular block, cardiogenic shock, and Adams Stokes Syndrome, who was initially misdiagnosed with fulminant myocarditis and was later found to have hypothyroidism during treatment.Summary: The child's condition did not improve after the administration of gamma globulin, methylprednisolone, and isoproterenol. Even after the placement of temporary pacemakers, the therapeutic effect was still not ideal. Upon reviewing the medical history, the child's condition improved rapidly after levothyroxine supplementation.Conclusions: Hypothyroidism is a common disease, but secondary severe cardiovascular lesions are particularly rare in children. Therefore, the delay in diagnosis can lead to serious cardiovascular manifestations. When pediatric patients develop severe AVB and bradycardia, hypothyroidism should be considered as a possible cause.

Background: Hypothyroidism can lead to bradycardia, reduced cardiac output, cardiac enlargement, and abnormal electrocardiogram. However, hemodynamic instability and malignant arrhythmias due to hypothyroidism is rarely reported in children.Patient Findings: We report the case of a child with third-degree atrioventricular block, cardiogenic shock, and Adams Stokes Syndrome, who was initially misdiagnosed with fulminant myocarditis and was later found to have hypothyroidism during treatment.Summary: The child's condition did not improve after the administration of gamma globulin, methylprednisolone, and isoproterenol. Even after the placement of temporary pacemakers, the therapeutic effect was still not ideal. Upon reviewing the medical history, the child's condition improved rapidly after levothyroxine supplementation.Conclusions: Hypothyroidism is a common disease, but secondary severe cardiovascular lesions are particularly rare in children. Therefore, the delay in diagnosis can lead to serious cardiovascular manifestations. When pediatric patients develop severe AVB and bradycardia, hypothyroidism should be considered as a possible cause.