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).

Intra-hospital complications during SARS-CoV2 infection

Introduction: The SARS-CoV2 virus has a respiratory tropism. Although pulmonary complications are most often in the foreground, other complications affecting other organs have been observed and associated with a greater bad prognosis. The aim of this work was to report the various complications observed in patients hospitalized with COVID-19 pneumonia. Method(s): We carried out a retrospective study from the records of patients treated for pneumonia COVID-19 hospitalized between March 2020 and July 2021. Result(s): We collected 578 patients aged between 18 and 98 years old. Thoracic complications were dominated by bronchial superinfection(4.3%), pericarditis(3.3%), pneumomediastinum(1.2%) and pneumothorax(0.8%). Among the thromboembolic complications, we counted 30 pulmonary embolisms(5.2%), 7 acute limb ischemia (1.2%), 2 strokes(0.3%) and 1 venous thrombosis deep(0.1%). Cardiac arrhythmias were observed in 6% of cases. Bradycardia sinusitis was observed in 14 patients (2.4%) and first degree atrioventricular block in 4 patients (0.7%). Acute heart failure occurred in 31 patients (5.3%). Neurological disorders were observed in 23 patients with agitation (4%) and hallucinations (1%). Acute renal failure was the most common metabolic complication (20%) followed by rhabdomyolysis (28%) and cytolysis hepatic (36%). Two patients presented with diabetic ketoacidosis (0.3%). Complications cardiac, neurological and renal were associated with a worse prognosis (p=0.001) and the pulmonary complications with longer hospitalization (p=0.01). Conclusion(s): SARS-CoV2 infection is a polymorphic disease. Identification of the different complications respiratory and extra respiratory is essential for rapid multidisciplinary care.

Primary Cardiac Lymphoma with an Aggressive Hostile Take-Over

Background Primary cardiac lymphoma (PCL) is an extranodal lymphoma involving only the heart and/or pericardium. PCL accounts for 2% of primary cardiac tumors and 0.5% of extranodal lymphomas. Its diagnosis is usually delayed due to rarity and non-specific findings. Case A 77-year-old man with Alzheimer dementia, atrial fibrillation on apixaban, and COVID-19 illness 3-weeks prior, who presented to the hospital with diffuse abdominal discomfort, fatigue, anorexia, and hypoactivity. Patient was tachycardic and normotensive with pronounced jugular venous distention, non-collapsing with respiration. ECG revealed sinus tachycardia, first degree atrioventricular (AV) block and chronic LBBB. Cardiac troponins were mildly elevated without significant delta. An abdominopelvic CT revealed an incidental, large pericardial effusion (PE). Bedside echocardiogram confirmed a large hemodynamically significant PE as well as a mass-like echogenicity encasing and infiltrating the pericardium and myocardium at the basal aspect of the right ventricle free wall. Decision-making In view of recent COVID-19 infection, he was started on indomethacin and colchicine for suspected viral or neoplastic pericarditis. Pericardiocentesis drained 900ml of amber to serosanguineous fluid with quick hemodynamic improvement. Fluid analysis was non-diagnostic for neoplasia. Subsequently, he developed symptomatic bradycardia with an intermittent complete AV block with junctional escape rhythm, transitioning to a second-degree AV block after removal of beta-blocker. Awaiting permanent pacemaker implant, he developed ventricular fibrillation with sudden cardiac death that required prolonged unsuccessful ACLS. Autopsy revealed an extensive infiltrative tumor, predominantly right-sided, consistent with primary cardiac B-cell lymphoma. Conclusion PCL should be part of the working diagnosis in patients presenting with a pericardial effusive process in combination with a right sided myocardial mass. Early cardiac MRI/PET scan or biopsy should be considered when the diagnosis is not certain. Prompt diagnosis could allow for treatment that potentially prolongs survival.Copyright © 2023 American College of Cardiology Foundation

Impinged RCA: Who's the Culprit?

Introduction: Post-sternotomy chest pain (CP) has been widely reported in literature. The etiologies include myocardial infarction, pulmonary embolism, hypersensitivity reactions to foreign material, wound infection, sternal instability and dehiscence, neuropathic pain due to intercoastal nerve damage or sternal wire fracture leading to migration. Here, we report a rare case of a young patient who presented with chronic chest pain after an atrial septal defect (ASD) repair. Case: A 28-year-old male with past medical history significant for an ASD (secundum) repair with autologous pericardial patch, hyperlipidemia, COVID-19 infection, known first degree AV block, and early repolarization changes, presented for a follow-up office visit three years after his ASD repair with complaints of typical anginal symptoms. Diagnosis: Vitals, physical exam, troponin, D-dimer and inflammatory markers were unremarkable. Chest x-ray (Figure 1A) showed sternal wires in place and no fractures of wires. EKG (Figure 1B) was unchanged. Echocardiogram showed LVEF 50% and no wall motion abnormalities. He underwent a coronary CTA which identified intermittent compression on the mid-RCA from the third bottom stainless steel sternal wire (Figure 1C), warranting removal. Treatment: He underwent explantation of all sternal wires and selective right coronary angiography (Figure 1D) was performed, which revealed intact and patent RCA without any complications. He continues to follow-up in our clinic without any CP. Conclusion(s): Chronic CP after any cardiac surgery remains a diagnostic dilemma and a source of anxiety for patients. We recommend comprehensive discussions with patients prior to surgery about these probable complications to alleviate the anxiety. Lastly, from research thus far, removal of sternal wires is a safe, simple, and effective procedure that should be offered to patients with persistent post-sternotomy CP after exclusion of serious complications.

Life-threatening rhythm and conduction disorders by a child with MIS-C

Background and Aim: Cardiac involvement is seen in the majority of cases with multisystem inflammatory syndrome in children (MIS-C). Various rhythm and conduction disturbances, as well as repolarization abnormalities, have been described by more than 50% of the patients, while there are few cases with complete heart block or with asystole. Method(s): Case report Results: 8-year old girl presented with a 5-day history of fever, cough, headache, and abdominal pain. Because of the critical con-dition, with respiratory insufficiency and heart failure symptoms, the child was intubated and started on inotropic support. ECG showed complete AV-block with a ventricular rate of 75/min and with ST-T changes;echocardiography revealed dilated left ventricle with reduced contractility, CT-scan of the lungs showed bilateral pneumonia, the inflammatory markers were elevated, in combination with high troponin levels, and positive SARS-CoV2-IgG antibodies. The diagnosis MIS-C was made and treatment with immunoglobulins, antibiotics, corticosteroids, and anticoagulants was initiated. During the next 2 days, the cardiac function deteriorated further, and while still on mechanical ventilation and inotropic support, extreme bradycardia with a ventricular rate of 35/min was regis-tered, and the patient was indicated for temporary emergency pac-ing. Upon induction of anesthesia, the child became asystolic, requiring extensive resuscitation. After circulation recovery, the ECG showed nodal tachycardia with a heart rate of 140-170/min. A temporary transvenous pacemaker (PM) was inserted, and the patient was started on intravenous amiodarone which resulted in a slower ventricular rate of 70/min. 3 days later sinus rhythm was restored, with first-degree AV-block, which allowed removal of the PM 5 days after its insertion. Left ventricular dimensions were normalized and contractility remained low-normal (EF 56%). During the 6-month follow-up, the ECG and the Holter-monitoring showed sinus rhythm with first-degree AV-block. Magnetic resonance imaging (MRI) on day 15 of the hospital stay demonstrated scattered areas of myocarditis and ischemia predominantly in the left ventricle, as well as thickening of the basal septum. Six months later the MRI changes were reduced but still persistent. Conclusion(s): MIS-C can present with serious and life-threatening rhythm and conduction disturbances in children;this is why extensive cardiac monitoring is obligatory by all patients.

A MULTIMODALITY IMAGING DIAGNOSIS OF A CHALLENGING CASE OF CONCOMITANT GROUP 1 PULMONARY HYPERTENSION AND PARADOXICALLY LOW- FLOW, LOW-GRADIENTAORTIC STENOSIS

A 76 year old woman was admitted to our hospital for self-limiting dyspnoea (NYHA class III) in oxygen dependence and frequent lipothymia following Valsalva manoeuvres. She was previously admitted to a Spoke Centre for heart failure (HF) with preserved ejection fraction (EF) and a new diagnosis of “pre-capillary pulmonary hypertension (PH)”. Despite a diagnosis of PH of unclear aetiology, she was started on macitentan without being reassessed for functional capacity due to Covid emergency;because of worsening symptoms, she was admitted to our Hub Centre. Resting ECG showed right axis deviation, right ventricle (RV) hypertrophy, first-degree atrioventricular block and right bundle branch block. Transthoracic echocardiography (TTE) showed reduced left ventricular (LV) volume with preserved EF (diastolic volume= 37 ml, EF=88%), severe right atrial and RV dilation with flattening of the interventricular septum, estimated pulmonary artery systolic pressure (PASP) of 124 mmHg, and moderate calcific aortic stenosis (peak aortic velocity 3.3 m/s, mean gradient 25 mmHg, valve area 1.1 cm2). Right and left heart catheterization showed severe pre-capillary PH (mean pulmonary pressure 60 mmHg, mean wedge 11 mmHg, pulmonary vascular resistance 14.41 WU), a severe aortic valve stenosis (aortic valve area 0.68 cmq and peak-to-peak gradient 25 mmHg, slight reduction of cardiac index 2.04 l/min/mq) and no significant coronary artery disease. The degree of aortic stenosis was considered as moderate-severe by integrating data of transesophageal echocardiography (planimetric area 1cm2) and assessment of calcium score (1615 Agatson units). Pneumological causes, chronic thromboembolic PH, rheumatologic diseases, HIV infection, paraneoplastic origin and veno-occlusive disease were all ruled out as potential PH causes and a diagnosis of Idiopathic pulmonary arterial hypertension (IPAH) was finally made. The Heart Team established the best therapeutic option was a transcatheter aortic valve replacement (TAVI) allowing better haemodynamic tolerability of PH therapy. The patient underwent TAVI and was started on PH therapy;a complete atrio-ventricular block developed after the procedure, requiring permanent pacemaker (PM) implantation. Unfortunately, few days later, the patient died following pacemaker's lead dislocation. Conclusion: PH has a diverse aetiology, and prognosis is generally poor, especially in patients with severe comorbidities. (Figure Presented).

Acute cardiovascular manifestations in children with multisystem inflammatory syndrome associated with COVID-19 infection in a Sicilian case series

Introduction: Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of COVID-19 infection, typically evidenced 4-6 weeks after the infection. The debated pathogenesis is a dysregulation of inflammatory response to SARS-CoV-2 infection ad a cytokine hyperexpression. Persistent fever, respiratory and gastrointestinal symptoms are the most common manifestations, associated with typical clinical signs described in Kawasaki Disease (KD). Furthermore, pleiomorphic cardiac manifestations are described, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, conduction abnormalities and pericardial effusion. These manifestations are a strong link with KD, even if in MIS-C they are more frequently documented. Severe cases can present as Toxyc Shock Syndrome (TSS) with vasodilatory or cardiogenic shock, requiring treatment with plasma expanders, inotropic drugs, diuretics, albumin and -in the more severe patients- extracorporeal membrane oxygenation and mechanical ventilation. KD experience guided the clinicians to treat these children with intravenous immunoglobulin (IVIG), steroids, aspirin (ASA) and, in refractory cases, anti-IL-1 monoclonal antibodies. Objectives: Most patients recover within days to a couple of weeks and mortality is rare, although the medium- and long-term sequelae, particularly cardiovascular complications, are not yet known. Methods: We describe the short-term outcome in a case series of 12 Sicilian children (4M;8F;age: 1.4-14 years) with MIS-C and a documented recent or actual infection by SARS-CoV-2 who showed cardiac involvement. Results: The cardiac features were: 3 patients showed pericardial effusion;1 coronaritis;6 transient mitral valve regurgitation;1 Brugada pattern, evidenced when he was febrile;2 showed associated mitral and aortic valve regurgitation). 7/8 patients with valve regurgitation showed a significant increase of pro-BNP, normalized during the follow-up. TSS was described in 2 patients, showing a significant increase of troponin, promptly treated with high dose of methylprednisolone, IVIG, vasoactive drugs, albumin and diuretics. 3 patients (21%), after the resolution of the acute phase, showed bradycardia (heart rate < 50/min), persisting for 7-10 days. The bradycardia was not associated with first-degree AVB, or a pathological PR. 6 patients (42%) showed an altered ventricular repolarization phase, in association with an increase of pro-BNP (129-3980 pg/ml). 4/12 (33%) had increased troponin levels (27.3-246 ng/ml) in the acute phase, with the normalization of troponin after IVIG and steroids treatment. Pro-BNP persisted increased for a longer time, besides the clinical improvement and the normalization of blood chemistry parameters. Conclusion: Generally, pro-BNP and troponin levels in MIS-C are higher than in KD, reflecting vasculopathy and cardiomyocytes damage extent. Persistence of increased levels of pro-BNP, in patients with a normalization of inflammatory parameters, suggests a mechanism of myocardial oedema, persisting besides the intensive care approach useful, however, to limit effects on cardiac function and normalize inflammatory parameters. Patients admitted with MIS-C require close electrocardiogram monitoring during the acute phase and the recovery, even if they do not manifest dyselectroliteemia, coronary lesions, pericardial effusion, myocarditis, shock. This approach can avoid severe arrythmia.