Background: Circulating platelet micro-RNAs (miRNAs) may be used to monitor platelet function during dual antiplatelet therapy (DAPT). Aim of the study was to measure plasma levels of specific miRNAs (miRNA-223, -150, -21 and -126) after physician-driven cessation of chronic P2Y12 inhibition and to study differences in the expression levels of these miRNAs between the different oral P2Y12 inhibitors clopidogrel, prasugrel and ticagrelor, respectively. Design: Patients with coronary artery disease (CAD) on DAPT maintenance dose (including aspirin 100 mg OD, plus clopidogrel 75 mg OD, or prasugrel 10 mg OD, or ticagrelor 90 mg BID) were prospectively enrolled before cessation of the P2Y12inhibitor therapy. MiRNA-223, -150, -21 and -126 were determined at baseline (=last day of P2Y12-inhibitor intake) and 10, 30 and 180 days thereafter. Results: Cessation of P2Y12-inhibitor therapy did not significantly change miRNA levels. However, in ticagrelor-treated patients, miRNA levels were significantly increased at baseline (miRNA-223 and -21), day 10 (miRNA-223, -150, -21, -126) and day 30 (miRNA-223, -150, -21, -126) as compared to prasugrel, and at day 10 (miRNA-150 and -21) and day 30 (miRNA-150) as compared to clopidogrel (all P < 0.05). At day 180, only miRNA-126 levels differed significantly with respect to the P2Y12 inhibitor used (P < 0.05). After adjustment for confounders, choice of P2Y12-inhibitor was the strongest predictor of miRNA levels (P < 0.001), while cessation of P2Y12-inhibitor therapy did not significantly impact miRNA levels. Conclusion: In patients with CAD, ticagrelor intake is associated with increased levels of platelet miRNAs as compared to clopidogrel and prasugrel. Platelet miRNAs are not useful to monitor platelet function after cessation of P2Y12 inhibitors. K E Y W O R D Sdual antiplatelet therapy, micro-RNA, P2Y12 inhibitor, platelet micro-RNA, prasugrel, ticagrelor Note: Therapy group (choice of P2Y12 inhibitor) was the strongest predictor of miRNA expression levels after correction for known and identified baseline differences. Time point did not significantly impact on miRNA levels.

IntroductionThe optimal duration of dual anti-platelet therapy (DAPT) following percutaneous coronary intervention (PCI) is still a matter of debate. Biomarkers may help to identify patients who will benefit from extended DAPT. The aim of the study was to test the interaction between lipid parameters and platelet function in patients with coronary artery disease (CAD) on DAPT.Material and methodsOverall, 58 patients on DAPT were prospectively included following PCI in stable CAD. Platelet markers, i.e. mean platelet volume (MPV), platelet distribution width (PDW), fraction of reticulated thrombocytes (RT) and ADP-induced multiple electrode aggregometry (MEA), as well as serum lipids, i.e. high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG) and remnant cholesterol (RC), were assessed after intake of a maintenance dose of ASA and P2Y12 inhibitor.ResultsA significant inverse correlation was found for HDL-C levels and markers of platelet activation: MPV (r = –0.351, p = 0.009), PDW (r = –0.391, p = 0.003), fraction of RT (r = –0.402, p = 0.003) and ADP-induced MEA (r = –0.345, p = 0.011). Only a weak or no association was found between other lipid parameters and platelet markers. After multivariable adjustment, HDL-C levels served as a strong and significant predictor of MPV (95% CI: –0.039 to –0.009; p = 0.002), PDW (95% CI: –0.094 to –0.034; p < 0.0001), RT (95% CI: –0.107 to –0.031; p = 0.001) and MEA (95% CI: –0.540 to –0.170; p < 0.0001), while TG, LDL-C, RC and TC were not significantly associated with platelet function.ConclusionsWithin lipid parameters, only HDL-C levels are strongly associated with markers of platelet activation in CAD patients on DAPT. Accordingly, detection of dyslipidemia might indicate the need for prolongation of DAPT.

IntroductionPediatric inflammatory multisystem syndrome – temporally associated with SARS-CoV-2 infection (PIMS –TS) comprises a new disease entity having emerged after the COVID-19 outbreak in 2019.Materials and MethodsFor this multicenter, retrospective study children between 0 and 18 years with PIMS-TS between March 2020 and May 2021 were included, before availability of vaccination for children. Frequent SARS-CoV-2 variants at that period were the wildtype virus, alpha, beta and delta variants. Inclusion criteria were according to the PIMS-TS criteria, proposed by the Royal College of Pediatrics and WHO. Study aim was to review their clinical, laboratory and echocardiographic data with a focus on cardiac involvement.ResultsWe report 45 patients, median age 9 years, 64% male. SARS-CoV-2 antibodies were positive in 35/41 (85%). PIMS occurrence followed local COVID-19 peak incidence periods with a time lag. The most common symptoms at presentation were fever (98%), abdominal pain (89%) and rash (80%). Fever history of &gt; 5 days was associated with decreased left ventricular function (p = 0.056). Arterial hypotension and cardiac dysfunction were documented in 72% patients, increased brain natriuretic peptide in 96% and increased cardiac troponin in 64% of the children. Echocardiography revealed mitral valve regurgitation (64%), coronary abnormalities (36%) and pericardial effusions (40%). Increased NT-proBNP was significantly associated with the need of inotropics (p &lt; 0.05), which were necessary in 40% of the patients. Treatment comprised intravenous immunoglobulin (93%), systemic steroids (84%) and acetylsalicylic acid (100%; 26/45 started with high dosages). For insufficient response to this treatment, five (11%) children received the interleukin-1 receptor antagonist anakinra. All patients were discharged with almost resolved cardiac signs.ConclusionOur analysis of non-vaccinated children with PIMS-TS demonstrates that a considerable number have associated myocarditis requiring intensive care and inotropic support. Most children showed adequate response to intravenous immunoglobulin and steroids and good recovery. Further evaluation of pediatric patients with COVID-19 associated diseases is required to evaluate the impact of new virus variants.

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Background To the best of our knowledge, this is the first report of a successful one-stage double atrioventricular valve (AVV) replacement using two Melody™ transcatheter valves in an infant. Case summary We report a successful case of double AVV replacement with Melody™ transcatheter valves in a 9-month-old infant with a right ventricular dominant atrioventricular septal defect (AVSD). The boy initially presented with borderline sized left-sided heart structures, congenital left AVV stenosis, ventricular displacement of the right AVV with high-grade insufficiency and moderate valvar pulmonary stenosis. Double AVV replacement was performed 2 months after an unsuccessful attempt to repair the defect with persisting left AVV stenosis, underfilling of the small left ventricle and high-grade right AVV, and pulmonary valve regurgitation, resulting in low cardiac output. During double Melody™ AVV replacement, the right ventricular outflow tract was replaced with a pulmonary homograft. The boy was discharged on post-operative Day 28 and presented with competent valves, no ventricular outflow tract obstruction and no paravalvular leak at 11 months of follow-up. Discussion The presented innovative approach allowed for biventricular correction of an unbalanced AVSD with unfavourable anatomy for standard techniques. The heart team should decide individualized, after careful assessment of cardiac anatomy and function, if the benefits of replacement of AVVs with Melody™ transcatheter valves may outweigh the benefits of univentricular palliation in case of unbalanced AVSD.