Clinical course and follow-up of pediatric patients with COVID-19 vaccine-associated myocarditis compared to non-vaccine-associated myocarditis within the prospective multicenter registry-"MYKKE".

BACKGROUND: Since the onset of widespread COVID-19 vaccination, increased incidence of COVID-19 vaccine-associated myocarditis (VA-myocarditis) has been noted, particularly in male adolescents. METHODS: Patients <18 years with suspected myocarditis following COVID-19 vaccination within 21 days were enrolled in the PedMYCVAC cohort, a substudy within the prospective multicenter registry for pediatric myocarditis "MYKKE." Clinical data at initial admission, 3- and 9-months follow-up were monitored and compared to pediatric patients with confirmed non-vaccine-associated myocarditis (NVA-myocarditis) adjusting for various baseline characteristics. RESULTS: From July 2021 to December 2022, 56 patients with VA-myocarditis across 15 centers were enrolled (median age 16.3 years, 91% male). Initially, 11 patients (20%) had mildly reduced left ventricular ejection fraction (LVEF; 45%-54%). No incidents of severe heart failure, transplantation or death were observed. Of 49 patients at 3-months follow-up (median (IQR) 94 (63-118) days), residual symptoms were registered in 14 patients (29%), most commonly atypical intermittent chest pain and fatigue. Diagnostic abnormalities remained in 23 patients (47%). Of 21 patients at 9-months follow-up (259 (218-319) days), all were free of symptoms and diagnostic abnormalities remained in 9 patients (43%). These residuals were mostly residual late gadolinium enhancement in magnetic resonance imaging. Patients with NVA-myocarditis (n=108) more often had symptoms of heart failure (P = .003), arrhythmias (P = .031), left ventricular dilatation (P = .045), lower LVEF (P < .001) and major cardiac adverse events (P = .102). CONCLUSIONS: Course of COVID-19 vaccine-associated myocarditis in pediatric patients seems to be mild and differs from non-vaccine-associated myocarditis. Due to a considerable number of residual symptoms and diagnostic abnormalities at follow-up, further studies are needed to define its long-term implications.

Severe heart failure and the need for mechanical circulatory support and heart transplantation in pediatric patients with myocarditis: Results from the prospective multicenter registry "MYKKE".

Myocarditis represents an important cause for acute heart failure. MYKKE, a prospective multicenter registry of pediatric patients with myocarditis, aims to gain knowledge on courses, diagnostics, and therapy of pediatric myocarditis. The role of mechanical circulatory support (MCS) in children with severe heart failure and myocarditis is unclear. The aim of this study was to determine characteristics and outcome of patients with severe heart failure requiring MCS and/or heart transplantation. The MYKKE cohort between September 2013 and 2016 was analyzed. A total of 195 patients were prospectively enrolled by 17 German hospitals. Twenty-eight patients (14%) received MCS (median 1.5 years), more frequently in the youngest age group (0-2 years) than in the older groups (P < 0.001; 2-12 and 13-18 years). In the MCS group, 50% received a VAD, 36% ECMO, and 14% both, with a survival rate of 79%. The weaning rate was 43% (12/28). Nine (32%) patients were transplanted, one had ongoing support, and six (21%) died. Histology was positive for myocarditis in 63% of the MCS group. Patients within the whole cohort with age <2 years and/or ejection fraction <30% had a significantly worse survival with high risk for MCS, transplantation, and death (P < 0.001). Myocarditis represents a life-threatening disease with an overall mortality of 4.6% in this cohort. The fulminant form more often affected the youngest, leading to significantly higher rate of MCS, transplantation, and mortality. MCS represents an important and life-saving therapeutic option in children with myocarditis with a weaning rate of 43%.

Extubation in the Operating Room After Fontan Procedure: Does It Make a Difference?

Early extubation appears to have beneficial effects on the Fontan circulation. The goal of this study was to assess the impact of extubation on the operating table in comparison with extubation during the first hours after Fontan operation (FO) on the early postoperative course. Between 2013 and 2016, 114 children with a single ventricle heart malformations (mean age, 3.8 ± 2.3 years) underwent FO: 60 patients were extubated in the operating room (ORE) and 54 in the intensive care unit (ICUE) in the median time of 195 min (range 30-515 min) after procedure. Pre-, peri-, and postoperative records were retrospectively analyzed. The hospital survival rate was 100%. One patient from the ORE group needed an immediate reintubation because of laryngospasm. The ORE group showed lower heart rate (106.5 vs. 120.3 bpm; p < 0.001) and lower central venous pressure (10.4 vs. 11.4 mmHg; p = 0.001) than patients in the ICUE group within the first 24 h after FO, as well as higher systolic blood pressure within 7 h after operation (88.6 ± 2.5 vs. 85.6 ± 2.6 mmHg; p = 0.036). The ORE children manifested significantly less pleural effusions during 48 h after FO (38.0 vs. 49.5 ml/kg; p = 0.004), received less intravenous fluid administration within 24 h after FO (54.1 vs. 73.8 ml/kg; p = 0.019), less inotropic support (9.8 vs. 12.8 h of dopamine; p = 0.033), and less antibiotics (4.7 vs. 5.8 days; p = 0.037). ICUE children manifested metabolic acidosis more frequently than the ORE group 3-4 h after FO (p < 0.05). Immediate extubation after FO in comparison with extubation in the ICU appears to be associated with improved hemodynamics and reduced application of therapeutic interventions in the postoperative course.

Use of dexmedetomidine in pediatric cardiac anesthesia.

PURPOSE OF REVIEW: In recent years, ultrafast-track anesthesia with on-table extubation and concepts of accelerated postoperative care have gained increasing support in pediatric congenital cardiac surgery. It is believed that such approaches might ideally combine economic benefits with a striving for continuous improvement of patient outcomes. The present review summarizes the role of dexmedetomidine (DEX) in this setting. RECENT FINDINGS: DEX is a clinical multipurpose drug that mediates its diverse responses through the activation of α2-adrenoreceptors. In pediatric cardiac surgery it has various applications. Used as a premedication, DEX provides arousable sedation and anxiolysis. As an intraoperative adjunctive agent of balanced general anesthesia the primary objectives for its administration are attenuation of the neuro-humoral stress response and facilitation of early extubation. During ICU treatment DEX spares opioids, prevents the risk of postoperative delirium or emergence agitation and impacts on important patient-centered outcomes, such as duration of mechanical ventilation, restart of enteral nutrition or length of ICU stay. SUMMARY: Due to a favorable mix of beneficial physiologic actions and a limited adverse effect profile, DEX is established in the perioperative pediatric cardiac surgery setting. However, evidence from high-quality randomized controlled trials on the effects of supplemental DEX on meaningful patient outcomes is scarce, and research on the role of DEX in providing cardioprotection, neuroprotection, or renoprotection is still at its beginning. DEX has developed to one of the main agents in the armamentarium of cardiac anesthesiologists and pediatric intensivists, but it should not be regarded as the new 'magic bullet'.

Toward evidence-based diagnosis of myocarditis in children and adolescents: Rationale, design, and first baseline data of MYKKE, a multicenter registry and study platform.

The aim of this registry is to provide data on age-related clinical features of suspected myocarditis and to create a study platform allowing for deriving diagnostic criteria and, at a later stage, testing therapeutic interventions in patients with myocarditis. STUDY DESIGN AND RESULTS: After an initial 6-month pilot phase, MYKKE was opened in June 2014 as a prospective multicenter registry for patients from pediatric heart centers, university hospitals, and community hospitals with pediatric cardiology wards in Germany. Inclusion criteria consisted of age<18 years and hospitalization for suspected myocarditis as leading diagnosis at the discretion of the treating physician. By December 31, 2015, fifteen centers across Germany were actively participating and had enrolled 149 patients. Baseline data reveal 2 age peaks (<2 years, >12 years), show higher proportions of males, and document a high prevalence of severe disease courses in pediatric patients with suspected myocarditis. Severe clinical courses and early adverse events were more prevalent in younger patients and were related to severely impaired leftventricular ejection fraction at initial presentation. SUMMARY: MYKKE represents a multicenter registry and research platform for children and adolescents with suspected myocarditis that achieve steady recruitment and generate a wide range of real-world data on clinical course, diagnostic workup, and treatment of this group of patients. The baseline data reveal the presence of 2 age peaks and provide important insights into the severity of disease in children with suspected myocarditis. In the future, MYKKE might facilitate interventional substudies by providing an established collaborating network using common diagnostic approaches.

Prognostic Value of Speckle Tracking Echocardiography-Derived Strain in Unmasking Risk for Arrhythmias in Children with Myocarditis.

Background/Objectives: Risk assessment in pediatric myocarditis is challenging, particularly when left ventricular ejection fraction (LVEF) is preserved. This study aimed to evaluate LV myocardial deformation using speckle-tracking echocardiography (STE)-derived longitudinal +strain (LS) and assessed its diagnostic and prognostic value in children with myocarditis. Methods: Retrospective STE-derived layer-specific LV LS analysis was performed on echocardiograms from patients within the multicenter, prospective registry for pediatric myocarditis "MYKKE". Age- and sex-adjusted logistic regression and ROC analysis identified predictors of cardiac arrhythmias (ventricular tachycardia, ventricular fibrillation, atrioventricular blockage III°) and major adverse cardiac events (MACE: need for mechanical circulatory support (MCS), cardiac transplantation, and/or cardiac death). Results: Echocardiograms from 175 patients (median age 15 years, IQR 7.9-16.5 years; 70% male) across 13 centers were included. Cardiac arrhythmias occurred in 36 patients (21%), and MACE in 28 patients (16%). Impaired LV LS strongly correlated with reduced LVEF (r > 0.8). Impaired layer-specific LV LS, reduced LVEF, LV dilatation, and increased BSA-indexed LV mass, were associated with the occurrence of MACE and cardiac arrhythmias. In patients with preserved LVEF, LV LS alone predicted cardiac arrhythmias (p < 0.001), with optimal cutoff values of -18.0% for endocardial LV LS (sensitivity 0.69, specificity 0.94) and -17.0% for midmyocardial LV LS (sensitivity 0.81, specificity 0.75). Conclusions: In pediatric myocarditis, STE-derived LV LS is not only a valuable tool for assessing systolic myocardial dysfunction and predicting MACE but also identifies patients at risk for cardiac arrhythmias, even in the context of preserved LVEF.

Clinical characteristics and outcome of biopsy-proven myocarditis in children - Results of the German prospective multicentre registry "MYKKE".

BACKGROUND: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis. METHODS: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint. RESULTS: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM. CONCLUSIONS: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE.

Impact of renin-angiotensin-aldosterone blockade by angiotensin-converting enzyme inhibitors or AT-1 blockers on frequency of contrast medium-induced nephropathy: a post-hoc analysis from the Dialysis-versus-Diuresis (DVD) trial.

BACKGROUND: After exposure to contrast medium (CM), about 10% of patients will develop contrast medium-induced nephropathy (CIN), with severe consequences for their prognosis. Although numerous studies evaluated risk factors for CIN development, it is still a matter of debate whether treatment with angiotensin-converting enzyme inhibitors (ACE-I) or AT-1 blockers increases the frequency of CIN after exposure to CM or not. METHODS: We performed a prospective, single-centre study (January 2001-July 2004) to compare different treatments for CIN prevention. Creatinine levels within 72 h after CM application and in-hospital outcomes were documented. The impact of RAAS blockade on the frequency of CIN was assessed retrospectively. RESULTS: Four hundred twelve patients were included (83.5% men, 29.1% diabetes mellitus, 74.6% hypertension). Of these, 269 patients (65.3%) were taking ACE-I (n = 236) or AT-1 blockers (n = 33). There were no significant differences in mean age (P = 0.075), creatinine levels (P = 0.113), gender (P = 0.281), diabetes mellitus (P = 0.172) or left ventricular ejection fraction (P = 0.09) between patients treated or not treated with RAAS blockade. Univariate analyses concerning development of CIN depending on treatment with RAAS blockade within 72 h found CIN to be significantly higher in patients treated with RAAS blockade (11.9 vs 4.2%, P = 0.006). Multivariate analyses (logistic regression) identified RAAS blockade to be an independent predictor of CIN (odds ratio 3.082, 95% confidence interval 1.234-7.698, P = 0.016). CONCLUSION: Patients treated with RAAS blockade before exposure to CM develop significantly more often CIN within 72 h. Even after adjustment for confounding comorbidities, treatment with ACE-I or AT-1 blockers turned out to be an independent risk predictor.

Impact of female gender on frequency of contrast medium-induced nephropathy: post hoc analysis of dialysis versus diuresis trial.

BACKGROUND: Of patients exposed to contrast medium (CM), 10% will develop contrast medium-induced nephropathy (CIN). Many studies have assessed potential risk factors for CIN. There are limited date concerning the influence of gender on frequency of CIN. METHODS: From January 2001 to July 2004, a prospective trial was performed to compare different treatments for CIN prevention. Creatinine levels (72 hours) were assessed, as well as in-hospital and long-term outcome. CIN was defined as in an increase of > or =25% or >0.5 mg/dL compared with baseline creatinine. The frequency of CIN in women and men was determined retrospectively. RESULTS: Four hundred twelve patients (67.1 +/- 10.2 years, 68 women) were randomized for different treatment strategies. Univariate analyses identified higher age (p = 0.031), diabetes (p = 0.03), decreased estimated glomerular filtration rate (eGFR) (p < 0.001), lower hemoglobin levels (p = 0.001), use of angiotensin-converting enzyme inhibitors (ACEI) (p = 0.004) and loop diuretics (p = 0.011), the amount of CM given (p < 0.001), and female gender to be associated with the occurrence of CIN within 72 hours. The frequency of CIN within 72 hours after CM administration was significantly higher in women than in men (p = 0.016). When CIN-associated factors were compared between women and men, women were older (69.8 vs. 66.5 years, p = 0.014) and had lower hemoglobin levels (12.6 vs. 13.8 g/dL, p < 0.001) and eGFR (35 vs. 49 mL/min, p < 0.001), suffered more often from diabetes (37% vs. 29%, p = 0.09), and had medication more frequently with loop diuretics (50% vs. 36%, p = 0.036) but not ACEI (56% vs. 57%, ns). The amount of CM given was identical (189 vs. 189 mL, ns). Multivariate analysis found female gender not to be an independent predictor of CIN (odds ratio [OR] 1.48, 95% confidence interval [CI] 0.72-3.02). CONCLUSIONS: Women are significantly more likely than men to suffer from CIN. This higher rate of CIN was confounded by unfavorable comorbidities, as found by univariate and multivariate analyses.