Changes in Kawasaki disease incidence and phenotype during the COVID-19 pandemic

INTRODUCTION. The aetiology of Kawasaki disease (KD) remains unknown. Changes in infectious exposure during the COVID-19 pandemic owing to infection prevention measures may have affected the incidence of KD, supporting the pathogenic role of an infectious trigger. The purpose of this study was to evaluate the incidence, phenotype and outcome of KD before and during the COVID-19 pandemic in Denmark. METHODS. This was a retrospective cohort study based on patients diagnosed with KD at a Danish paediatric tertiary referral centre from 1 January 2008 to 1 September 2021. RESULTS. A total of 74 patients met the KD criteria of whom ten were observed during the COVID-19 pandemic in Denmark. Alof these patients were negative for SARS-CoV-2 DNA and antibodies. A high KD incidence was observed during the first six months of the pandemic, but no patients were diagnosed during the following 12 months. Clinical KD criteria were equally met in both groups. The fraction of intravenous immunoglobulin (IVIG) non-responders was higher in the pandemic group (60%) than in the in the pre-pandemic group (28.3%), although the rate of timely administered IVIG treatment was the same in both groups (>= 80%). Coronary artery dilation was observed in 21.9% in the pre-pandemic group compared with 0% in KD patients diagnosed during the pandemic. CONCLUSION. Changes in KD incidence and phenotype were seen during the COVID-19 pandemic. Patients diagnosed with KD during the pandemic had complete KD, higher liver transaminases and significant IVIG resistance but no coronary artery involvement.Copyright © 2023, Almindelige Danske Laegeforening. All rights reserved.

Cardiac Involvement in Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) in Poland.

Multisystem inflammatory syndrome in children (MIS-C) is an immune-mediated complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Cardiovascular system is commonly involved. Acute heart failure (AHF) is the most severe complication of MIS-C, leading to cardiogenic shock. The aim of the study was to characterise the course of MIS-C with a focus on cardiovascular involvement, based on echocardiographic (echo) evaluation, in 498 children (median age 8.3 years, 63% boys) hospitalised in 50 cities in Poland. Among them, 456 (91.5%) had cardiovascular system involvement: 190 (48.2%) of patients had (most commonly atrioventricular) valvular insufficiency, 155 (41.0%) had contractility abnormalities and 132 (35.6%) had decreased left ventricular ejection fraction (LVEF < 55%). Most of these abnormalities improved within a few days. Analysis of the results obtained from two echo descriptions (a median of 5 days apart) revealed a >10% increase in LVEF even in children with primarily normal LVEF. Lower levels of lymphocytes, platelets and sodium and higher levels of inflammatory markers on admission were significantly more common among older children with contractility dysfunction, while younger children developed coronary artery abnormality (CAA) more often. The incidence of ventricular dysfunction might be underestimated. The majority of children with AHF improved significantly within a few days. CAAs were relatively rare. Children with impaired contractility as well as other cardiac abnormalities differed significantly from children without such conditions. Due to the exploratory nature of this study, these findings should be confirmed in further studies.

Complications Of A Severe Case Of Multisystem Inflammatory Syndrome In Children

Case Presentation: A 10 year old male with prior COVID-19 exposure presented with 7 days of fever, rash, cough, vomiting, and hypotension. Laboratory evaluation was notable for SARS-CoV2 antibodies, elevated cardiac enzymes, BNP, and inflammatory markers. Initial echocardiogram showed normal cardiac function and a small LAD coronary aneurysm. He was diagnosed with Multisystemic Inflammatory Syndrome in Children (MIS-C) and given methylprednisolone and IVIG. Within 24 hours, he developed severe LV dysfunction and progressive cardiorespiratory failure requiring VA-ECMO cannulation and anticoagulation with bivalirudin. Cardiac biopsy demonstrated lymphocytic infiltration consistent with myocarditis. On VA-ECMO, he had transient periods of complete AV block. With immunomodulator treatment (anakinra, infliximab) and 5 days of plasmapheresis, inflammatory symptoms and cardiac function improved. He weaned off ECMO, and anticoagulation was transitioned to enoxaparin. He had left sided weakness 5 days later, and brain MRI revealed an MCA infarct. Ten days later, he had focal right sided weakness and repeat MRI showed multiple hemorrhagic cortical lesions, thought to be thromboembolic with hemorrhagic conversion secondary to an exaggerated inflammatory response to an MSSA bacteremia in the setting of MIS-C. Enoxaparin was discontinued. After continued recovery and a slow anakinra and steroid wean, he has normal coronary arteries, cardiac function, and baseline ECG but requires ongoing neurorehabilitation. Discussion(s): COVID-19 infection in children is often mild, but MIS-C is an evolving entity that can present with a wide range of features and severity. This case highlights two concepts. While first degree AV block is often reported in MIS-C, there is potential for progression to advanced AV block. Close telemetry monitoring is critical, especially if there is evidence of myocarditis. MIS-C shares features with Kawasaki disease, with a notable difference being a higher likelihood of shock and cardiac dysfunction in MIS-C. In MIS-C patients with cardiovascular collapse requiring ECMO, there is a risk for stroke. There should be a low threshold for neuroimaging and multidisciplinary effort to guide anticoagulation in these complex cases.

Atrio-Ventricular Conduction Abnormalities in Multisystem Inflammatory Syndrome in Children

Purpose of study Since mid-April 2020 in Europe and North America, clusters of pediatric cases with a newly described severe systemic inflammatory response with shock have appeared. Patients had persistent fevers >38.5 C, hypotension, features of myocardial dysfunction, coagulopathy, gastrointestinal symptoms, rash, and elevated inflammatory markers without other causes of infection. The World Health Organization, Centers for Disease Control, and Royal College of Paediatrics associated these symptoms with SARS-CoV-2 as multisystem inflammatory syndrome in children (MIS-C). Cardiac manifestations include coronary artery aneurysms, left ventricular systolic dysfunction evidenced by elevation of troponin-T (TnT) and pro-B-type naturietic peptide (proBNP), and electrocardiogram (ECG) abnormalities. We report the clinical course of three children with MIS-C while focusing on the unique atrioventricular (AV) conduction abnormalities. Case #1:19-year-old previously healthy Hispanic male presented with abdominal pain, fever, and non-bloody diarrhea for three days. He was febrile and hypotensive (80/47 mmHg) requiring fluid resuscitation. Symptoms, lab findings, and a positive COVID-19 antibody test were consistent with MIS-C. Methylprednisolone, intravenous immunoglobulin (IVIG), and enoxaparin were started. He required epinephrine for shock and high flow nasal cannula for respiratory distress. Initial echocardiogram demonstrated a left ventricular ejection fraction (LVEF) of 40% with normal appearing coronaries. Troponin and proBNP were 0.41 ng/mL and proBNP 15,301 pg/mL respectively. ECG showed an incomplete right bundle branch block. He eventually became bradycardic to the 30s-50s and cardiac tracing revealed a complete AV block (figure 1a). Isoproterenol, a B1 receptor agonist, supported the severe bradycardia until the patient progressed to a type 2 second degree AV block (figure 1b). A second dose of IVIG was administered improving the rhythm to a type 1 second degree AV block. An IL-6 inhibitor, tocilizumab was given as the rhythm would not improve, and the patient soon converted to a first-degree AV block. Cardiac magnetic resonance imaging showed septal predominant left ventricular hypertrophy and subepicardial enhancement along the basal inferior/anteroseptal walls typical for myocarditis. Case #2: 9-year-old previously healthy Hispanic male presented after three days of daily fevers, headaches, myalgias, diffuse abdominal pain, and ageusia. He was febrile, tachycardic, and hypotensive (68/39 mmHg). Hypotension of 50s/20s mmHg required 3 normal saline boluses of 20 ml/kg and initiation of an epinephrine drip. Severe hypoxia required endotracheal intubation. After the MIS-C diagnosis was made, he was treated with IVIG, mehtylprednisolone, enoxaparin, aspirin, and ceftriaxone. Due to elevated inflammatory markers by day 4 and patient's illness severity, a 7-day course of anakinra was initiated. Initial echocardiogram showed mild tricuspid and mitral regurgitation with a LVEF of 35-40%. Despite anti-inflammatory therapy, troponin and proBNP were 0.33 ng/mL and BNP of 25,335 pg/mL. A second echocardiogram confirmed poor function so milrinone was started. Only, after two doses of anakinra, LVEF soon normalized. Despite that, he progressively became bradycardic to the 50's. QTc was prolonged to 545 ms and worsened to a max of 592 ms. The aforementioned therapies were continued, and the bradycardia and QTc improved to 405 ms. Patient #3: 9-year-old African American male presented with four days of right sided abdominal pain, constipation, and non-bilious non-bloody emesis. He had a negative COVID test and unremarkable ultrasound of the appendix days prior. His history, elevated inflammatory markers, and positive COVID- 19 antibody were indicative of MIS-C. He was started on the appropriate medication regimen. Initial ECG showed sinus rhythm with normal intervals and echocardiogram was unremarkable. Repeat imaging by day three showed a decreased LVEF of 50%. ECG had since changed to a right bundle branch block. Anakinra as started and steroid dosing was increased. By day 5, he became bradycardic to the 50s and progressed to a junctional cardiac rhythm. Cardiac function normalized by day 7, and anakinra was subsequently stopped. Thereafter, heart rates ranged from 38-48 bpm requiring transfer to the pediatric cardiac intensive care unit for better monitoring and potential isoproterenol infusion. He remained well perfused, with continued medical management, heart rates improved. Methods used Retrospective Chart Review. Summary of results Non-specific T-wave, ST segment changes, and premature atrial or ventricular beats are the most often noted ECG anomalies. All patients initially had normal ECGs but developed bradycardia followed by either PR prolongation or QTc elongation. Two had mild LVEF dysfunction prior to developing third degree heart block and/or a junctional escape rhythm;one had moderate LVEF dysfunction that normalized before developing a prolonged QTc. Inflammatory and cardiac markers along with coagulation factors were the highest early in disease course, peak BNP occurred at approximately hospital day 3-4, and patient's typically had their lowest LVEF at day 5-6. Initial ECGs were benign with PR intervals below 200 milliseconds (ms). Collectively the length of time from initial symptom presentation till when ECG abnormalities began tended to be at day 8-9. Patients similarly developed increased QTc intervals later in the hospitalization. When comparing with the CRP and BNP trends, it appeared that the ECG changes (including PR and QTc elongation) occurred after the initial hyperinflammatory response. Conclusions Although the mechanism for COVID-19 induced heart block continues to be studied, it is suspected to be secondary to inflammation and edema of the conduction tissue. Insufficiency of the coronary arterial supply to the AV node and rest of the conduction system also seems to play a role. Although our patients had normal ECG findings, two developed bundle branch blocks prior to more complex rhythms near the peak of inflammatory marker values. Based on the premise that MIS-C is a hyperinflammatory response likely affecting conduction tissue, our group was treated with different regimens of IVIG, steroids, anakinra, and/or tocilizumab. Anakinra, being an IL-1 inhibitor, has been reported to dampen inflammation in viral myocarditis and tocilizumab has improved LVEF in rheumatoid arthritis patients. Based on our small case series, patient's with MISC can have AV nodal conduction abnormalities. The usual cocktail of IVIG and steroids helps;however, when there are more serious cases of cardiac inflammation, adjuvant immunosuppresants like anakinra and toculizumab can be beneficial. (Figure Presented).

Multisystemic Inflammatory Syndrome in Children and Kawasaki Disease: Parallels in Pathogenesis and Treatment.

PURPOSE OF REVIEW: Since it first appeared, multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease 2019 (COVID-19) has been compared to Kawasaki disease (KD). Although there were early parallels between MIS-C and KD, key differences emerged over time. Here, we aim to compare the pathogenesis, clinical presentation, treatment, and outcomes of MIS-C and KD. RECENT FINDINGS: In this article, we review and compare MIS-C and KD, highlighting differentiating features. We discuss the epidemiological and immunological factors along with clinical and laboratory features which discern MIS-C from KD. We also compare treatment and our understanding of long-term outcomes. Though parallels exist between MIS-C and KD, distinguishing the two is important for clinical management of patients, counseling about natural history, and determining long-term monitoring. While both MIS-C and KD are characterized by profound inflammation and inflammatory vasculopathy, further study is needed to determine whether they are distinct immunopathogenic disorders.

Incomplete Kawasaki Disease with Peripheral Facial Nerve Palsy and Lung Nodules: A Case Report and Literature Review.

The diagnosis of Kawasaki disease (KD) is challenging and often delayed mainly in case of young infants and in presence of an incomplete disease and atypical features. Facial nerve palsy is one of the rare neurologic symptoms of KD, associated with a higher incidence of coronary arteries lesions and may be an indicator of a more severe disease. Here, we describe a case of lower motor neuron facial nerve palsy complicating KD and perform an extensive literature review to better characterize clinical features and treatment of patients with KD-associated facial nerve palsy. The patient was diagnosed at the sixth day of disease and presented extensive coronary artery lesions. A prompt treatment with intravenous immunoglobulins, aspirin and steroids obtained a good clinical and laboratory response, with resolution of facial nerve palsy and improvement of coronary lesions. The incidence of facial nerve palsy is 0.9-1.3%; it is often unilateral, transient, more frequent on the left and seemingly associated with coronary impairment. Our literature review showed coronary artery involvement in the majority of reported cases (27/35, 77%) of KD with facial nerve palsy. Unexplained facial nerve palsy in young children with a prolonged febrile illness should prompt consideration of echocardiography to exclude KD and start the appropriate treatment.

An Update on Reports of Atypical Presentations of Kawasaki Disease and the Recognition of IVIG Non-Responder Children.

Kawasaki disease (KD) is an acute vasculitis with an intrinsic risk of severe involvement of coronary arteries. The worldwide spread of KD and the importance of early diagnosis for preventing cardiovascular complications have ascertained the need for updating guidelines for prompt disease recognition and treatment efficacy assessment. All KD patients who comply with the definition of classic or atypical disease should be treated with intravenous immunoglobulin (IVIG) soon after diagnosis. The objective of our narrative review was to analyze the medical literature about case reports with atypical KD in relation to diagnosis and potential identification of predictors of non-responsiveness to IVIG. Our analysis has shown that the seminal challenge in KD management is the timeliness of diagnosis, although both extreme variability and transience of clinical manifestations make this goal difficult. A non-negligible percentage of patients, especially in the first 6 months of life, might have atypical manifestations of KD, whose painstaking differential diagnosis may be tricky. Many attempts to develop universal scoring systems and detect children at higher risk of IVIG resistance have been rather unsuccessful. Additionally, KD may show different evolutions according to unraveled demographic, genetic, or epigenetic factors. Further research is needed to elucidate all open questions about KD and clarify the long-term outcome of its potential complications.

Kawasaki Disease in Children and Pediatric Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 During the Pandemic (Clinical Lecture).

The article presents modern data about Kawasaki disease, which is a genetically determined systemic vasculitis with damage to the coronary arteries and multisystem manifestations. The etiology is not fully understood, but there is considered a possible role of viruses in the initiation of the aggravated immune response with possible development of macrophage activation syndromes and shock, which can lead to death. There are difficulties in diagnosing Kawasaki disease due to a variety of symptoms that are typical for a lot of infectious and autoimmune diseases (scarlet fever, measles, yersiniosis, systemic juvenile idiopathic arthritis). Early diagnosis and treatment (in the first 10 days of illness) using high doses of intravenous immunoglobulin and aspirin are associated with a low risk of development of coronary aneurysms and other complications. The authors also presented the data on the characteristics of severe Kawasaki-like diseases, which were recorded in several countries of Europe and America at the peak of the COVID-19 pandemic, and diagnostic criteria for the pediatric multisystem inflammatory syndrome associated with SARS-CoV-2, proposed by the Royal College of Pediatrics and Children Health (UK).Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

Kawasaki Disease in Children and Pediatric Multisystem Inflammatory Syndrome Associated with SARS-CoV-2 During the Pandemic (Clinical Lecture).

The article presents modern data about Kawasaki disease, which is a genetically determined systemic vasculitis with damage to the coronary arteries and multisystem manifestations. The etiology is not fully understood, but there is considered a possible role of viruses in the initiation of the aggravated immune response with possible development of macrophage activation syndromes and shock, which can lead to death. There are difficulties in diagnosing Kawasaki disease due to a variety of symptoms that are typical for a lot of infectious and autoimmune diseases (scarlet fever, measles, yersiniosis, systemic juvenile idiopathic arthritis). Early diagnosis and treatment (in the first 10 days of illness) using high doses of intravenous immunoglobulin and aspirin are associated with a low risk of development of coronary aneurysms and other complications. The authors also presented the data on the characteristics of severe Kawasaki-like diseases, which were recorded in several countries of Europe and America at the peak of the COVID-19 pandemic, and diagnostic criteria for the pediatric multisystem inflammatory syndrome associated with SARS-CoV-2, proposed by the Royal College of Pediatrics and Children Health (UK).Copyright © 2020, Professionalnye Izdaniya. All rights reserved.

It's not the shunt: an atypical cause of fever in an infant with hydrocephalus

Case Report:We present a 5-year-old male with two days of fever, cough, vomiting, and loose stools. His history is significant for premature birth (35 weeks gestational age) and shunted hydrocephalus. A ventriculoperitoneal (VP) shunt was placed 6 days prior to presentation. Parental report included episodes of post-tussive, nonbloody, non-bilious emesis, poor oral intake, tachypnea, and increased work of breathing. Physical examination demonstrated a dehydrated infant with sunken fontanelles. He had no notable rash, no lymphadenopathy, and clear conjunctiva. His VP shunt site appeared normal without swelling or erythema. Initial evaluation showed elevated inflammatory markers -ESR 51 and CRP 12.32 mg/dL. A viral respiratory PCR panel returned positive for coronavirus (not SARS-CoV-2). A head CT scan and shunt radiography series showed no abnormalities with his shunt. The following morning, Radiology reported an incidental retropharyngeal fluid collection on a re-read of the patient's initial CT scan. A neck CT was obtained and demonstrated a fluid pocket with secondary mass effect in addition to bilateral cervical lymphadenopathy. Screening blood cultures were negative. The patient remained febrile (tmax 103.6F) and developed a transaminitis (ALT 264.9, AST 654), elevated fibrinogen 476, elevated INR 1.4, and low albumin 2.1. Abdominal ultrasound showed a normal the liver and biliary tract. His transaminitis resolved without treatment. The next day, the patient developed lip erythema and conjunctival injection. An echocardiogram showed a dilated right coronary artery (z-score of 3.59) and his inflammatory markers (ESR 26, CRP 9.63) remained elevated. Treatment was initiated with IVIG and moderate-dose aspirin. The patient defervesced, and he remained afebrile for over 48 hours prior to discharge. A repeat echocardiogram 2 days later showed a slight reduction in coronary artery dilatation (z-score 3.39). Hewas discharged on lowdose aspirin, and followed up with cardiology as an outpatient. Kawasaki's Disease (KD) is most common in children from ages 1 to 4 years and is classically characterized by persistent fever with a constellation of symptoms including limbal sparing conjunctivitis, cervical lymphadenopathy, polymorphous rash, strawberry tongue, oral changes, and extremity changes. Our patient presented at a younger age with a concurrent diagnosis of coronavirus upper respiratory tract infection. His atypical hospital course and incidental finding of retropharyngeal edema and transaminitis increased the clinical suspicion for KD. His symptoms rapidly improved after administration of IVIG. Younger patients are at an increased risk for severe complications of KD including coronary aneurysm. KD has been shown in the literature to have an association with coronavirus infection as well as presentation with retropharyngeal edema. Clinicians should consider KD in their differential even if patients do not meet all criteria for diagnosis on initial presentation. Copyright © 2023 Southern Society for Clinical Investigation.

Clinical phenotypes of multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19

The multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C) is infre-quent but potentially lethal. There are few reports of this disease and its phenotypes in Latin America. Objective(s): To describe the characteristics of the clinical phenotypes of MIS-C in hospitalized patients in Lima, Peru. Patients and Method: A descriptive and retrospective study in patients under 14 years old with a diagnosis of MIS-C at the Hospital Nacional Edgardo Rebagliati Martins (Lima, Peru), from April 2020 to August 2021. Clinical-demographic and microbiological variables were recorded. According to these, patients with MIS-C were classified into the shock phenotype, Kawasaki disease (KD) without shock, and the fever and inflammation phenotype, analyzing their clinical outcomes. Result(s): 58 patients were analyzed. 32 (55.2%) presented the shock phenotype, 15 (25.8%) Kawasaki disease (KD) phenotype without shock, and 11 (19%) fever and inflammation phenotype. In the shock phenotype, 17 had KD. The mean age was 7 +/- 3.5 years and 67.2% were males. Gastrointes-tinal and mucocutaneous manifestations predominated in all phenotypes. The mortality was 3.5%. The frequency of coronary aneurysms was 10.2%. Most patients received immunomodulatory and antiplatelet treatment. Patients with shock phenotype showed greater involvement in inflammatory markers, hematological dysfunction, and myocardial injury, with a higher frequency of respiratory failure and invasive mechanical ventilation. Conclusion(s): In our case series, patients with shock phenotype were the most frequent and had worse clinical outcomes. Active surveillance of clinical phenotypes is needed to make an early diagnosis and management to improve the prognosis in these patients. Copyright © 2022, Sociedad Chilena de Pediatria. All rights reserved.

Coronary artery aneurysm presenting as ST-elevation myocardial infarction in a man with coronavirus disease 2019: a case report.

BACKGROUND: Patients with underlying cardiovascular risk factors have worse clinical outcomes when they have coronavirus disease. In addition, a reduced workload of cardiovascular emergencies has been reported during the coronavirus pandemic due to patients' reluctance to attend hospitals for fear of contracting the disease. Regional health service reorganization, separating hospitals into coronavirus and non-coronavirus can mitigate this effect. However, the effectiveness of this approach on outcomes and patient satisfaction is unknown. CASE PRESENTATION: A 35-year-old Pakistani man with acute ST myocardial infarction was found to have thrombosis of the right coronary artery aneurysm and concomitant coronavirus disease. He had percutaneous coronary angiography and thrombus removal, and was transferred to a coronavirus hospital for the management of the infection. Due to the large size of the aneurysm, he was considered for surgical intervention. Following discharge from the coronavirus hospital and a period of stay at the isolation center, he failed to keep his cardiology follow-up appointment. CONCLUSION: This case illustrates an unusual cause of myocardial infarction in a patient with coronavirus infection whose care may have been adversely affected by the healthcare system restructuring.

Interventional challenges in vasculitis

Background: This case highlights how coronary pathology presents in vasculitis. Case presentation: A 49-year-old male, never-smoker presented to our hospital for a series of Acute Coronary Syndromes (ACS). The first in October 2019;angiogram revealed diffuse aneurysms and clot in the right coronary artery (RCA) and stenosis in the posterolateral branch (PLB). Post aspiration thrombectomy, and drug eluting stent (DES) to the PLB, patient was discharged on standard ACS meds. Coagulopathy workup was unremarkable. Follow up in November 2020, the patient was recommended reducing ticagrelor to 60mg twice daily (bid). The second ACS, one year later, revealed severe in-stent restenosis of the PLB stent. Patient had 2 DES placed in the PLB and was discharged on escalated therapy of rivaroxaban 2.5mg bid, and ticagrelor 90mg bid. Two months later the patient had COVID-19;during that admission he had two ACS events. The first showing mid-RCA stenosis and thrombosis of the same PLB;this was treated with only angioplasty. The next day, he had repeat ACS showing thrombosis of the RCA, but despite multiple attempts RCA recanalization was unsuccessful and discharged on medical therapy only. During clinic follow up, May 2022, the patient revealed that he had Kawasaki's disease as a kid. Conclusion(s): Coronary aneurysms are high risk because of slow flow and endothelial dysfunction that makes balloon dilation, stent sizing, and post interventional medical therapy difficult. Currently no standard guidelines exist to help providers treat this population. It may be beneficial to regularly follow up, monitor inflammatory markers (ESR, CRP correlated well with interleukin 6 and 8), and use CT or PET to follow active vasculitis and changes in aneurysms. Kawasaki's disease is a vasculitis of small and medium-sized vessels and often presents in childhood. Prospective studies show that patients with coronary aneurysms tend to have systemic artery aneurysms, so it is important to screen other arterial beds. Valvular disease has also been found to co-exist in patients with vasculitis, and pre-existing disease should be followed with echocardiography.

An Unwelcome House Guest: Coronary Aneurysms and Evolving Stemi

Case Description: 54-year-old man presented to the Emergency Department (ED) three weeks after Covid-19 infection for progressively worsening dyspnea and hypoxemia. Dexamethasone and prophylactic apixaban (2.5mg twice a day) were initiated and he was discharged 48 hours later. A week after discharge he re-presented to the ED requiring 6L of oxygen (O ) despite uninterrupted dexamethasone and apixaban therapy. His past medical history was significant for quiescent IgG4 disease on Rituximab and Type 1 Diabetes. He was afebrile, tachycardic and tachypneic with decreased right lower lobe breath sounds. He had an elevated erythrocyte sedimentation rate and C-reactive protein, no leukocytosis and no pulmonary embolism of CT. He was admitted and vancomycin and cefepime antibiotic therapy for a superimposed bacterial pneumonia was begun. On day 12 of the hospital stay, he experienced new onset chest pain. Evaluation showed an elevated troponin and submillimeter ST segment elevation concerning for an evolving STEMI. Coronary angiography demonstrated an 90% diffuse mid LAD stenosis and two large coronary aneurysms of the left circumflex artery (LCx). The mid-LAD was stented using a 3.0 x 38 mm and 2.75 x 26 mm Onyx drug eluting stents with resolution of his chest pain. IgG4 serum level was normal and imaging did not demonstrate active IgG4 disease. He was discharged on aspirin and clopidogrel. Due to concern for a hypercoagulable state in the setting of Covid 19 infection, IgG4 disease and the large coronary aneurysms for thrombus formation, warfarin anticoagulation was also initiated. On review of his coronary imaging, the largest LCx aneurysm was 9mm on admission and 12mm three weeks later with evidence of diffuse coronary inflammation. CT Fractional Flow Reserve (abnormal <= 0.80) demonstrated decreased flow at the distal aneurysm with no focal stenosis to account for flow reduction. Conclusion(s): 54-year-old man with IgG4 disease presenting with prolonged Covid-19 infection and acute NSTEMI. He was found to have large, flow limiting coronary aneurysms and inflamed coronary arteries all consistent with his IgG4 disease. Management of these aneurysms will be discussed.

Mortality and Clinical Characteristics of Multisystemic Inflammatory Syndrome in Children (Mis-C) Associated with Covid-19 in Critically Ill Patients in a Middleincome Country: Observational Multicenter Study

BACKGROUND AND AIM: The clinical presentation and severity of (MIS-C) presents a very low mortality in high-income countries. This research describes clinical characteristics of MIS-C in critically ill children in middleincome countries and factors associated with mortality and critical outcomes. METHOD(S): Observational cohort study in 14 (PICUs) in Colombia between April 2020 -January 2021. Patient age from one month to18 years, that met WHO requirements for MIS-C. RESULT(S): There were 78 children in this study. The median age was seven years (IQR 1-11), 18 % (14/78) were under one year old. 35 % of patients (29/78) were obese or overweight. 100 % had fever upon arrival to the clinic lasting at least five days (IQR 3.7-6). 70 % (55/78) of patients had diarrhea, and 87% (68/78) shock or systolic myocardial dysfunction (78 %), 35% (27/78) coronary aneurysms, and pericardial effusion in 36 %.There was a higher mortality rate compared to high in-come countries (9 % vs. 1.8 %;p=0.001). When assessing the group of patients who died, ferritin levels was above 500 ngr/mL (100 % vs. 45 %;p=0.012), as well as more cardiovascular complications (100 % vs. 54 %;p = 0.019). CONCLUSION(S): MIS-C in critically ill children living in a middle-income country has some clinical, laboratory, and echocardiographic characteristics, similar to high-income countries. Inflammatory response and cardiovascular involvement added to the difficulties in accessing the healthcare system in limited resources countries, could explain the greater mortality seen. Prospective studies are needed to compare the differences found in MIS-C outcomes between countries with different income.

Immune and non-immune mechanisms that determine vasculitis and coronary artery aneurysm topography in Kawasaki disease and MIS-C.

The overlap between multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease (KD) including coronary artery aneurysms (CAA) and broadly shared gastrointestinal and mucocutaneous disease is poorly defined. In this perspective, we highlight common age-related extravascular epicardial microanatomical and immunological factors that might culminate in CAA expression in both MIS-C and KD. Specifically, the coronary vasa vasorum originates outside the major coronary arteries. Widespread inflammation in the epicardial interstitial compartment in shared between KD and MIS-C. Age-related changes in the neonatal and immature coronary vasculature including the impact of coronary artery biomechanical factors including coronary vessel calibre, age-related vessel distensibility, flow, and vessel neurovascular innervation may explain the decreasing CAA frequency from neonates to older children and the virtual absence of CAA in young adults with the MIS-C phenotype. Other KD and MIS-C features including mucocutaneous disease with keratinocyte-related immunopathology corroborate that disease phenotypes are centrally influenced by inflammation originating outside vessel walls but a potential role for primary coronary artery vascular wall inflammation cannot be excluded. Hence, common extravascular originating tissue-specific responses to aetiologically diverse triggers including superantigens may lead to widespread interstitial tissue inflammation characteristically manifesting as CAA development, especially in younger subjects. Given that CAA is virtually absent in adults, further studies are needed to ascertain whether epicardial interstitial inflammation may impact on both coronary artery physiology and cardiac conduction tissue and contribute to cardiovascular disease- a hitherto unappreciated consideration.

Approach to a child with pediatric inflammatory multisystem syndrome with COVID-19 recommendations by the Polish pediatric society expert group and the national consultant in the field of pediatrics

Pediatric inflammatory multisystem syndrome associated with COVID-19 (PIMS) is a new entity, occurring in children and young adults, associated with the SARS-CoV-2 infection. The first cases of PIMS were found in Poland in May 2020. Since October 2020, a significant increase in the incidence of this new disease has been observed in Poland, which reflects the increased incidence of COVID-19 in adults. PIMS development results from dysregulation of the immune system occurring after 2-4 weeks after the SARS-CoV-2 in-fection. Diagnosis is based on a set of clinical features (including fever and features of mul-tiple organ damage) and laboratory abnormalities, with the exclusion of other causes. Most common complications involve cardiovascular system: myocarditis with decreased left ven-tricular ejection fraction, shock and/or coronary artery aneurysms. Mortality is around 2%. Appropriate management, including vital functions support and immunomodulating treat-ment, allows for a quick recovery of the vast majority of patients. The following document is a proposal for diagnostic and therapeutic management of children with suspected PIMS in Poland. Copyright © 2020, Wydawnictwo Czelej Sp. z o.o.. All rights reserved.

Assessing medium term cardiac outcomes in children with multi-system inflammatory syndrome

Background and Aim: Multi-system inflammatory syndrome in chil-dren (MIS-C) causes widespread systemic inflammation including a pancarditis in the weeks following a COVID infection. Further coronavirus surges appear inevitable and with vaccination rates lower in young people an understanding of the medium-term car-diac impacts of this condition is important for planning further treatment and understanding the impacts on their health. Method(s): A retrospective single-center study of 67 consecutive patients with MIS-C was performed. Three time points were determined as the point of worst cardiac dysfunction during the acute admission, then at intervals of 6-8 weeks and 6-8 months. Echocardiographic findings were used to evaluate both 2D and 3D measures of cardiac function. Coronary artery measurements were recorded. Corresponding serial ECG findings were evaluated. Result(s): The worst cardiac function arose 6.8 +/- 2.4 days after the onset of fever. The mean M mode-derived FS was 30.9 +/- 8.1% during the acute phase. The mean 3D left ventricle (LV) ejection fraction (EF) was borderline at 50.5 +/- 9.8%. A pancarditis was typ-ically present: 46.3% showed cardiac impairment;31.3% had some pericardial effusion;26.8% had moderate (or worse) valvar regur-gitation and;26.8% had coronary dilatation. Cardiac function returned to normal in all patients by 6-8 weeks (mean 3D LV EF 61.3 +/- 4.4%, plt;0.001 compared to admission). Coronary dila-tation normalized in all but one patient who initially developed large aneurysms at presentation;these continued 6 months later. ECG findings mainly featured T-wave changes resolving at fol-low-up. There were a small number of adverse events: need for ECMO (2), death as an ECMO-related complication (1), suben-docardial infarction (1), LV thrombus formation (1). Conclusion(s): MIS-C causes a pancarditis with decreased cardiac function and almost a quarter of patients showing coronary changes. In most, discharge from long-term follow-up can be con-sidered as full cardiac recovery is expected by 8 weeks. The excep-tion includes patients with medium sized aneurysms or greater or those with more of a Kawasaki disease phenotype as these require on-going surveillance for persistence of coronary changes.

Kawasaki disease and the current SARS-COV-2 pandemic: Rare lessons from a cohort of more than 1000 kawasaki patients in the netherlands

Background and Aim: Kawasaki disease (KD) is a paediatric vasculitis with an unknown aetiology. The aim of this study was to assess the clinical course, treatment and cardiovascular outcomes in children with KD. The secondary purpose of this study was to make a com-parison with the Kawasaki-like disease Multisystem Inflammatory Syndrome in Children (MIS-C), which is triggered by SARS-CoV-2. Method(s): In this observational cohort study, clinical information from KD and MIS-C patients was collected. Data were described and a multivariate analysis was performed to identify risk factors for coronary artery aneurysms (CAAs). Clinical characteristics between KD and MIS-C were compared using chi-squared and Mann-Whitney U tests. Result(s): 1003 KD patients were included. The male-to-female ratio was 3:2, a majority of the patients were lt;5 years old (78.3%), treated with a single dose of intravenous immunoglobulin (IVIG) (90.8%) and treated promptly (lt;10 days) (81.7%). A second dose of IVIG was needed in minority of the patients (24.7%). The main complication of KD were CAAs and known risk factors (i.e., male, young age, delayed treatment) for CAAs were confirmed. A total of 35 MIS-C patients were included for the comparison. These patients were older than the KD patients (Plt;0.0005), more often had an incomplete KD presentation (Plt;0.0005). MIS-C patients mainly presented with acute cardiac dysfunction, with complete recovery after treatment. Conclusion(s): KD and MIS-C are severe post-infectious inflamma-tory diseases. Due to the risk of cardiovascular complications, vigi-lance and prompt treatment are advised to reduce risk of cardiovascular complications.

Echocardiographic Evaluation of Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19

Cardiac involvement is an observable issue in multisystem inflammatory syndrome in children (MIS-C) associ20 ated with COVID-19. The most common echocardiographic findings in MIS-C are abnormal coronary arteries, decreased left ventricular function, mitral regurgitation, and pericardial effusion. Abnormalities in the coronary arteries were seen in less than 20% of MIS-C patients. These abnormalities include dilatation or aneurysms in the coronary arteries;however, giant or large aneurysms are rare. On the other hand, transient coronary artery dilatation (which can occur secondary to viral myocarditis) may also mean that the coronary artery Z-scores never exceed 2.5. Reviewing large case series revealed that approximately 30 - 40% of MIS-C patients had decreased left ventricular function. In most cases, left ventricular function is mildly depressed, and severe left ventricular dysfunction was observed in only one-fifth of cases. Hypoxia, myocardial ischemia secondary to coronary involvement, stress-induced cardiomyopathy, injury caused by systemic inflammation, and viral myocarditis are the possible etiologies for the myocardial injury in MIS-C. It is now clear that myocardial strain imaging indices such as a global longitudinal strain (GLS), end-diastolic strain rate (EDSR), and peak left atrial strain (LAS) can demonstrate systolic or diastolic dysfunction in myocarditis patients with preserved left ventricular ejection fraction. Furthermore, right-sided ventricular deformation imaging abnormalities have been reported in adult patients with MIS-C. Less information is currently available on mitral regurgitation and pericardial effusion in pediatric patients with MIS-C;however, in an extensive study on 286 pediatric patients with MIS-C, 28% had pericardial effusion, and 42.7% had mitral regurgitation;both were mild in most patients.