Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children.

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vß21.3 T cell receptor ß chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vß21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vß21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

Value of preoperative echocardiography for the diagnosis of coronary artery patterns in neonates with transposition of the great arteries.

BACKGROUND: Abnormal coronary pattern may complicate coronary transfer during arterial switch operation. OBJECTIVE: To evaluate the accuracy of echocardiography in assessing the anatomy of coronary arteries in neonates with transposition of the great arteries, and determine impact on outcomes. METHODS: We conducted a retrospective analysis of data in neonates with transposition of the great arteries. Preoperative echocardiographic coronary artery pattern and surgical intraoperative reports were compared. Mismatch between transthoracic echocardiography and surgical intraoperative reports and the impact on perioperative outcome were assessed. Coronary patterns were classified into four groups: type 1 (normal); type 2 (risk of coronary with intramural course); type 3 (coronary loop); and type 2+3. RESULTS: Overall, 108 neonates who underwent an arterial switch operation were included: 68 were classified as type 1; seven as type 2; 32 as type 3; and one as type 2+3. Overall, 10 adverse events occurred. Five patients died, three from coronary causes. Survival was 96% at 1 month. Transthoracic echocardiography and surgical intraoperative reports differed in 17.6% of cases. Mortality was 15.8% in case of inappropriate diagnosis and 2.2% for appropriate diagnosis (P=0.01). Mortality in type 2 was 66.7% in case of discordance versus 0% when concordant. Multivariable analysis found that inappropriate preoperative transthoracic echocardiography diagnosis of coronary pattern was the only significant risk factor for mortality (P=0.04). CONCLUSIONS: Echocardiography can assess coronary artery anatomy in neonates with transposition of the great arteries. Intramural coronary course is often misdiagnosed. Preoperative misdiagnosis of coronary artery anomaly may impact perioperative mortality. However, this assessment will have to be confirmed by further larger studies.

Follow-up of children or teenagers with paroxysmal supraventricular tachycardia, but without pre-excitation syndrome.

BACKGROUND: Paroxysmal supraventricular tachycardia (SVT) is considered benign in children if the electrocardiogram in sinus rhythm is normal, but causes anxiety in parents, children and doctors. AIMS: To report on the clinical and electrophysiological data from children with SVT, their follow-up and management. METHODS: Overall, 188 children/teenagers (mean age 15±2.8 years) with a normal electrocardiogram in sinus rhythm were studied for SVT, and followed for 2.3±4 years. RESULTS: SVT was poorly tolerated in 30/188 children (16.0%). SVT was related to atrioventricular nodal reentrant tachycardia (AVNRT) (n=133) or atrioventricular reentrant tachycardia (AVRT) over a concealed accessory pathway (n=55; 29.3%). Ablation of the slow pathway (n=66) or the accessory pathway (n=43) was performed without general anaesthesia, 2±3 years after initial evaluation. Failure or refusal to continue occurred in 18/109 (16.5%) children: 7/66 with AVNRT (10.6%), 11/43 with AVRT (25.6%) (P<0.001). Symptoms of SVT recurred in 20/91 children (22.0%) with apparently successful ablation: 6/91 (6.6%) had real SVT recurrence; 14/91 (15.4%) had only a sinus tachycardia, more frequent in AVNRT (11/59; 18.6%) than AVRT (3/32; 9.4%) (P<0.05). In 13 children treated with an antiarrhythmic drug (AAD), SVT recurred in four; two presented AAD-related syncope. In 66 untreated children, one death was noted after excessive AAD infusion to stop SVT; the others remained asymptomatic or had well-tolerated SVT. CONCLUSIONS: At the time of ablation, SVT management remains difficult in children. Indications for ablation are more common in AVRT than in AVNRT, but failures are frequent; 22.0% remained symptomatic after successful ablation, but false recurrences were frequent (15.4%). Without ablation, one third had a spontaneous favourable evolution.

[Sports in children with congenital heart diseases]. / Sport et cardiopathies congénitales chez l'enfant.

The practice of physical activity is one of the essential elements for health in general but also for the well-being and the quality of life. It is highly desirable to encourage physical activities in children with congenital heart diseases, taking into account all the benefits associated with this practice (quality of life, life expectancy) and this especially since these children often have limited capacity (due to their heart disease but also often by relative deconditioning). While there is a transient increase in risk of cardiac complications during intense activity, it would nevertheless be inappropriate to contra-indicate physical activities considering the well-known benefits in the medium and long term. The risks associated with the practice of physical activity must be assessed, on one hand, in terms of the severity of the heart disease, and on the other hand, on the nature and intensity of the activity. The stress test is here an essential tool because it helps to assess the physical capacity and cardiorespiratory adaptations to exercise. The international recommendations for competitive sports generally give an appropriate advice for a specific situation but the practice of moderate activity or leisure sports which are highly desirable should not be neglected and be strongly encouraged.

Evolution of Clinical and Electrophysiological Data in Children with a Preexcitation Syndrome.

BACKGROUND: With ablation, the follow-up of preexcitation syndrome now is difficult to assess. The purpose was to collect data of children with a preexcitation syndrome studied on two separate occasions within a minimal interval of 1 year. METHODS: This is a retrospective chart review of 47 children initially aged 12 ± 4 years, who underwent two or more invasive electrophysiological studies (EPS) within 1-25 years of one another (6.3 ± 4.8) for occurrence of symptoms or new evaluation. RESULTS: Among initially symptomatic children (n = 25), four (19%) became asymptomatic and one presented life-threatening arrhythmia. Among asymptomatic children (n = 22), five became symptomatic (22.7%). Anterograde conduction disappeared in seven of 23 children with initially long accessory pathway-effective refractory period, but four of six had still induced atrioventricular reentrant tachycardia (AVRT). AVRT was induced at second EPS in three of 13 asymptomatic preexcitation syndrome with negative initial EPS. There were no spontaneous adverse events in the five children with criteria of malignancy at initial EPS; signs of malignancy disappeared in two. At multivariate analysis, AVRT at initial EPS was the only independent factor of symptomatic AVRT during follow-up. Absence of induced AVRT at initial EPS was the only factor of absence of symptoms and a negative study at the second EPS. CONCLUSIONS: There were no significant changes of data in children after 6.3 ± 4.8 years of follow-up. Most children with spontaneous/inducible AVRTs at initial EPS had still inducible AVRT at second EPS. Induced AF conducted with high rate has a relatively low prognostic value for the prediction of adverse events.

Electrophysiological study generally is negative in patients <40 years suspected of supraventricular tachycardia but also complaining of chest pain and/or syncope.

BACKGROUND: The diagnosis of paroxysmal supraventricular tachycardia (SVT) frequently is a dilemma. Electrophysiological study (EPS) is the only means to evaluate the nature of symptoms when noninvasive studies remain negative. Our objectives were to determine the clinical factors of negativity or positivity of (EPS) in patients suspected of SVT. METHODS: EPS was performed in 2650 patients complaining of tachycardia and suspected of SVT. Transesophageal EPS consisted of programmed atrial stimulation in control state and after isoproterenol. Patients were followed from 1 month to 18 years (2.93 ± 4 years). RESULTS: SVT was induced in 1944 patients, age 48 ± 19.5. EPS remained negative in 706 patients, age 34 ± 17 (p<0.0001). Age <40 years, feeling of dizziness/syncope or chest pain associated with tachycardia, the absence of heart disease or short PR interval was more frequent in patients with negative EPS (respectively 64, 42, 26, 96, 88.5%) than in patients with induced SVT (34, 14, 4, 88, 59%) (p<0.0001).The positive predictive value for the prediction of a negative EPS of age <40, chest pain, syncope or their association was 63.5, 42, 26.5, 11% and negative predictive value was 66, 86, 94.5, 99.5%. At multivariate analysis, age <40 (0.000, OR 2.79), the presence of syncope associated with tachycardia (0.000, OR 5.075) or chest pain (0.000, OR 17.923) was an independent factor of negative EPS. CONCLUSIONS: Among patients complaining of nondocumented tachycardia, suspected of SVT, the association of tachycardia with chest pain and/or syncope and age <40 years generally was correlated with a negative EPS and did not indicate initially invasive studies. In the remaining patients transesophageal EPS is indicated.

AV nodal reentrant tachycardia or AV reentrant tachycardia using a concealed bypass tract-related adverse events.

OBJECTIVES: To jointly study paroxysmal supraventricular tachycardia (SVT)-related adverse events (AE) and ablation-related complications, with specific emphasis on the predictors of SVT-related AE as well as their significance by investigating their association with long-term mortality. METHODS: 1770 patients were included, aged 6 to 97, with either atrioventricular nodal reentrant tachycardia (AVNRT) or orthodromic atrioventricular reciprocal tachycardia (AVRT) mediated by concealed accessory pathway, consecutively referred for SVT work-up in a tertiary care center. RESULTS: SVT-related AE were identified in 339 patients (19%). Major AEs were identified in 23 patients (1%; 15 cardiac arrests or ventricular arrhythmias requiring cardioversion and 8 hemodynamic collapses). Other AE were related to syncope (n=236), acute coronary syndrome (n=57) and heart failure/rhythmic cardiomyopathy (n=21). In multivariable analysis, higher age, heart disease and requirement of isoproterenol to induce SVT were independently associated with a higher risk for SVT-related AE. During follow-up (2.8±3.0years), death occurred more frequently in patients with SVT-related AE, especially in patients with major adverse events (p<0.001). In multivariable analysis, major SVT-related AE remained significantly associated with occurrence of death (HR=6.72, IC=(2.58-17.52), p<0.001) independently of age and presence of underlying heart disease. Major SVT-related AE in the whole population referred for SVT were more frequent than immediate major ablation complications in patients undergoing SVT ablation (5/1186 vs. 23/1770, p=0.02). CONCLUSIONS: SVT-related AE are independent predictors of mortality and are more frequent than immediate major ablation complications in patients undergoing SVT ablation. The present findings support systematically performing SVT ablation in patients with SVT-related adverse events.

Factors of negativity of electrophysiological study in children and teenagers complaining of tachycardia and prognostic significance.

When non-invasive studies remain negative, the diagnosis of unexplained tachycardia in the young is a dilemma. The purpose of the study was to determine the factors of negativity of transesophageal electrophysiological study (EPS) in children/teenagers complaining of tachycardia and the prognostic value. Two hundred and seventy-three children with a normal ECG in sinus rhythm, aged from 6 to 19 years (15 ± 3), complained of tachycardia. Transesophageal EPS consisted of atrial stimulation in control state and after isoproterenol. Supraventricular tachycardia (SVT) was induced in 149 patients (group I) and EPS remained negative in 124 (group II). Age did not differ (15 ± 3 vs 15 ± 3). Female gender and familial history of SVT were as frequent in group I (47, 11%) than in group II (55%, p = 0.15; 7%;p = 0.2). Feeling of dizziness/syncope with tachycardia was less frequent in group I (12%) than in group II (48%) (p < 0.0001). Feeling of chest pain with tachycardia was less frequent in group I (2%) than in group II (28%) (p < 0.0001). The presence of non-cardiac disease was less frequent in group I (1.3%) than in group II (6.4%) (p < 0.025). Patients with negative study remained free of SVT after a follow-up of 3.5 ± 3 years, but one had a complete AV block. In children with apparently normal ECG in sinus rhythm, who complained of tachycardia clinical history (association with syncope, chest pain, or the presence of another disease) can predict negativity of EPS with a relatively high accuracy; EPS may not be necessary. In very symptomatic patients, transesophageal EPS, which is inexpensive and non-invasive, might be performed to stop investigations.

Age-related location of manifest accessory pathway and clinical consequences.

BACKGROUND: Accessory pathway (AP) ablation is not always easy. Our purpose was to assess the age-related prevalence of AP location, electrophysiological and prognostic data according to this location. METHODS: Electrophysiologic study (EPS) was performed in 994 patients for a pre-excitation syndrome. AP location was determined on a 12 lead ECG during atrial pacing at maximal preexcitation and confirmed at intracardiac EPS in 494 patients. RESULTS: AP location was classified as anteroseptal (AS)(96), right lateral (RL)(54), posteroseptal (PS)(459), left lateral (LL)(363), nodoventricular (NV)(22). Patients with ASAP or RLAP were younger than patients with another AP location. Poorly-tolerated arrhythmias were more frequent in patients with LLAP than in other patients (0.009 for ASAP, 0.0037 for RLAP, <0.0001 for PSAP). Maximal rate conducted over AP was significantly slower in patients with ASAP and RLAP than in other patients. Malignant forms at EPS were more frequent in patients with LLAP than in patients with ASAP (0.002) or PSAP (0.001). Similar data were noted when AP location was confirmed at intracardiac EPS. Among untreated patients, poorly-tolerated arrhythmia occurred in patients with LLAP (3) or PSAP (6). Failures of ablation were more frequent for AS or RL AP than for LL or PS AP. CONCLUSIONS: AS and RLAP location in pre-excitation syndrome was more frequent in young patients. Maximal rate conducted over AP was lower than in other locations. Absence of poorly-tolerated arrhythmias during follow-up and higher risk of ablation failure should be taken into account for indications of AP ablation in children with few symptoms.

Arterial switch operation with a single coronary artery: the autograft concept.

A single coronary artery, especially if associated with anterior looping, remains a risk factor when performing an arterial switch operation for transposition of the great arteries. In such a situation, to avoid the risk of overstretching, we used a modification of the aortic autograft concept to transfer the single coronary artery, resulting in a tension-free relocation.