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Background: Cases of adolescents and young adults developing myocarditis after vaccination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–targeted mRNA vaccines have been reported globally, but the underlying immunoprofiles of these individuals have not been described in detail. Methods: From January 2021 through February 2022, we prospectively collected blood from 16 patients who were hospitalized at Massachusetts General for Children or Boston Children’s Hospital for myocarditis, presenting with chest pain with elevated cardiac troponin T after SARS-CoV-2 vaccination. We performed extensive antibody profiling, including tests for SARS-CoV-2–specific humoral responses and assessment for autoantibodies or antibodies against the human-relevant virome, SARS-CoV-2–specific T-cell analysis, and cytokine and SARS-CoV-2 antigen profiling. Results were compared with those from 45 healthy, asymptomatic, age-matched vaccinated control subjects. Results: Extensive antibody profiling and T-cell responses in the individuals who developed postvaccine myocarditis were essentially indistinguishable from those of vaccinated control subjects, despite a modest increase in cytokine production. A notable finding was that markedly elevated levels of full-length spike protein (33.9±22.4 pg/mL), unbound by antibodies, were detected in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t test; P Conclusions: Immunoprofiling of vaccinated adolescents and young adults revealed that the mRNA vaccine–induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. However, free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis, advancing insight into its potential underlying cause.

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. Methods: We retrospectively collected data on patients Results: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1–20.3; interquartile range [IQR], 14.5–17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0–22; IQR, 1–3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0–10; IQR, 2–3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50–15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25–1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction Conclusions: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with substantial cardiovascular implications. Although infection with SARS-CoV-2 is usually mild in children, some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease. This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children. Although the prevalence is unknown, >600 cases have been reported in the literature. Multisystem inflammatory syndrome in children appears to be more common in Black and Hispanic children in the United States. Multisystem inflammatory syndrome in children typically occurs a few weeks after acute infection and the putative etiology is a dysregulated inflammatory response to SARS-CoV-2 infection. Persistent fever and gastrointestinal symptoms are the most common symptoms. Cardiac manifestations are common, including ventricular dysfunction, coronary artery dilation and aneurysms, arrhythmia, and conduction abnormalities. Severe cases can present as vasodilatory or cardiogenic shock requiring fluid resuscitation, inotropic support, and in the most severe cases, mechanical ventilation and extracorporeal membrane oxygenation. Empirical treatments have aimed at reversing the inflammatory response using immunomodulatory medications. Intravenous immunoglobulin, steroids, and other immunomodulatory agents have been used frequently. 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. This review describes the published data on multisystem inflammatory syndrome in children, focusing on cardiac complications, and provides clinical considerations for cardiac evaluation and follow-up.

Introduction: The American Heart Association (AHA) guidelines recommend testing for inducible myocardial ischemia in all patients with a history of coronary artery aneurysm (CAA) after Kawasaki disease (KD). Because the prevalence of clinical coronary complications is exceedingly low in patients whose worst-ever CAA dimension was Methods: Retrospective study including patients Results: A total of 588 stress tests were performed in 208 patients at median age of 12.4 [IQR 8.8, 16.8] years, 8.3 [IQR 5.0, 12.9] years after diagnosis (Table). Tests were performed using either exercise stress (545 [93%] tests) or pharmacologic stress with dobutamine (43 [7%] tests). Echocardiography was the most frequently used modality (n=481, 82%), followed by nuclear imaging (n=133, 23%) and cardiac MRI (n=53, 9%). Inducible ischemia was found on 11 (2%) tests in 6 (3%) patients. All patients with inducible ischemia had a history of giant CAA with persistent CAA at time of testing (moderate CAA in 2 (18%) tests, giant CAA in 9 (82%) tests). After finding inducible ischemia on stress test, coronary artery bypass grafting was performed in 3 cases, cardiac catheterization in 4, stress testing using a different imaging modality in 1, and careful clinical monitoring without intervention in 3. Conclusions: Inducible ischemia was found in 2% of test after KD, and only in patients with a history of giant CAA. Recommendations in the 2017 AHA guidelines for KD for testing for myocardial ischemia in patients with non-giant CAA should be reconsidered in light of these findings.

Background: Diagnosis of Kawasaki Disease (KD) can be confusing in the absence of a confirmatory test or pathognomonic finding, especially when clinical criteria are incomplete (iKD). We have lately proposed serum NT-proBNP as an adjunctive diagnostic test. Method: We retrospectively tested a new diagnostic algorithm to aid in diagnosis based on NT-proBNP (Z-score for age), coronary artery dilation (CAD) at onset, and abnormal serum albumin or CRP. The goal was to assess the performance of the algorithm with respect to CAD outcome (aneurysm, dilation, or occult dilation). Occult dilation is defined as variation of coronary artery Z-score >2 within the normal range ( Results: The algorithm was tested on 81 KD patients who had NT-proBNP on admission at our institution between 2008 and 2013. Age at diagnosis was 3.2 ± 2.6 years, with a median of 5 diagnostic criteria (range 3-6), of whom 31/81 (38.3%) had iKD. Aneurysms occurred in 16/81 (19.8%); higher prevalence in iKD, 12/31 (38.7%) versus 4/50 (8.0%) (p=0.001). CAD affected 35/81 (43.2%), and 30/81 (37.0%) had occult CAD. With the algorithm, 80/81 (98.8%) were to be treated: based on high NT-proBNP alone for 54/81 (66.7%), on onset CAD for 13/81 (16.0%), and on high CRP or low albumin for 13/81 (16.0%). (Figure 1) Results were similar when the algorithm was applied to patients with complete or incomplete criteria. The only patient “not-to-treat” with the algorithm had iKD and transient occult CAD. Conclusion: This NT-proBNP based algorithm is efficient to identify and treat patients at risk of coronary involvement, despite an apparent selection bias of CA involvement. This paves the way for a prospective validation trial of the algorithm.

Background: Coronary artery aneurysms (CAA) are a serious complication of Kawasaki disease (KD). Coronary imaging usually describes aneurysms, stenosis and dilatation. Optical coherence tomography (OCT) is a technique useful for intracoronary imaging and coronary wall structure characterization. Method: KD patients scheduled for routine coronary angiography underwent OCT imaging between June 2013 and August 2014. Subjects’ clinical courses with echocardiography and angiography were reviewed to contrast with OCT findings. Results: OCT was performed on 18 patients 9.0 ± 5.1 years after KD at 12.4 ± 5.5 yo (range 3.5-21 yo). Of those, 14 (77.7%) had a history of CAA (7 giant CAA, 7 regressed CAA at time of OCT). Prophylactic intracoronary nitroglycerin was given (88.4 ± 45.5 μg/m2). Total X-ray exposure was 10.9 mGy/kg. One patient had a transitory uneventful vasospasm at the site of a former CAA, otherwise no major complications occurred (such as dissection, thrombosis, ischemia, arrhythmia). OCT findings were intimal hyperplasia in 15/18 (83.3%) on aneurysmal and regressed aneurysm segments. Intimal hyperplasia measured 390.8 ± 166.0 μm for the affected segments, compared to 61.7 ± 17.0 μm for the unaffected segments (p Conclusion: In our experience, OCT proved safe and insightful in the setting of KD. The observed coronary structural changes correspond to histological findings described in the literature late after KD.

Introduction: Statistical mathematical processing of medical imaging promotes operator-independent interpretation. We sought to identify discriminative image features for a histological disambiguation of KD related coronary (CA) lesions. The ultimate goal is to develop a fully automated algorithm for the quantification of the degradation/healing state of the CA wall structure post KD. Methods: We analyzed OCT CA recordings from two KD patients with (KD + AN + ) and two patients with no history of CA aneurysm (KD + AN [[Unable to Display Character: –]] ), vs a non KD patient (KD [[Unable to Display Character: –]] ). Results: In KD [[Unable to Display Character: –]] , regardless of the radial region of interest (ROI) position in the image, the OCT mean signal intensity presents centrifugally two peaks corresponding to the intima and media, constantly separated (17.1± 2.0 pixels) (fig. 1A). In KD + AN [[Unable to Display Character: –]] the peaks may disappear (Fig. 1-B left medial hyperplasia) and the distance between remaining crests vary between ROIs (22.7±6.9 Pixels). In KD + AN + these peaks disappear (Figure1-C) and the signal intensity changes drastically between ROIs due to wall restructuration. Figure1-C shows a hatched signal that maybe that of a laminar structure. In this case the variation of gradient intensity may be a discriminative feature. Conclusion: Mathematical modeling of CA wall layers is feasible. While the consistency of the distance between media and intima peaks may discriminate KD [[Unable to Display Character: –]] from KD + and while the gradient intensity may detect restructuration in KD + AN + , ongoing investigation to discriminate CA lesions include signal homogeneity, energy and contrast. Texture analysis with anatomical correlates (e.g., calcium, fibrosis and clots) may allow automated diagnoses.

Background: Coronary artery aneurysms (CAA) are a serious complication of Kawasaki disease (KD). Regression of CAA occurs in 50% of the cases on follow up. Actual imaging techniques often described these segments as normal, whereas studies have shown significant endothelial and smooth muscle dysfunction. Method: KD patients scheduled for angiographic follow-up between June 2013 and August 2014 underwent OCT imaging. We compared coronary intimal changes in coronary artery segments with no history of CAA to segments with regressed CAA, and segments with persistent CAA. The intima was measured in sections adjacent to the CAA for the segments with persistent CAA, at the former CAA and adjacent sections for those who regressed, and at various corresponding sections for segments with no history of CAA. Results: OCT was performed on 18 patients at 12.4 ± 5.5 years. Overall 14/18 (77.7%) had a history of CAA. Of those, 7/14 (50.0%) had regressed CAA at time of OCT. Data was analyzed according to echocardiographic and angiographic progress of CAA segments. Accordingly, all 18/18 persistent CAA segments and 11/11 regressed CAA segments had significant intimal hyperplasia, compared to 1/13 with no history of segmental CAA (P Conclusion: Despite normal angiographic features, regressed CAA segments displayed significant intimal hyperplasia, similarly to those with persistent CAA. These features may present a risk of adverse coronary events.

Background: Coronary artery aneurysms (CAA) develop in up to 30% of untreated patients with Kawasaki disease (KD). This may lead to ischemic heart disease and sudden cardiac death, which is extremely rare nowadays. Method: A 3 mo infant presented with severe KD 27 days after onset of fever. He died few days later of multi vessel obstruction and aneurysms. OCT was performed post mortem and correlated with pathology findings. Results: The patient presented with shock, inferolateral ischemia on ECG and high Troponin-i (from 6.45 to 59 μg/L 2 days later). Echocardiography showed severe myocardial dysfunction with diffuse coronary dilation and right CAA. Arterial Doppler demonstrated thrombosis of aneurysmal axillary, subclavian and iliac arteries, which corroborated with clinically ischemic limbs. Withdrawal of support was implemented due to multiorgan failure. OCT images from the proximal RCA, LAD, carotid and pulmonary arteries were obtained post mortem. The circumflex coronary could not be accessed by the OCT catheter, which was occluded on pathology exam. The carotid (figure TOP) and pulmonary arteries were normal on OCT and histology. RCA and LAD (figure BOTTOM) showed aneurysmal dilatation, with marked intimal hyperplasia and preserved media on OCT. Pathology confirmed these findings, with destruction of internal elastic lamina, luminal myofibroblastic proliferation, neovascularization, and attenuation of the media in some sections. Conclusion: This is the first report of pathologic correlation in a severe KD case with OCT imaging at the sub-acute stage, which adequately identified structural wall changes.