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Parameters of the interaction of the left atrium and left ventricle, atrioventricular (AV) coupling, are used in the diagnosis and follow-up of diastolic dysfunction in adults. Pediatric parameters of AV coupling have not been evaluated so far. The aim of this multicenter study was to investigate parameters of AV coupling in a large cohort of healthy infants and children using noninvasive real-time three-dimensional echocardiography. The authors hypothesized that the contribution of the different left atrial (LA) volumes to left ventricular (LV) stroke volume differs over a range of different heart rates.Three-dimensional echocardiographic data sets from 332 subjects (ages 0 days to 18.5 years) were analyzed prospectively. Volume-time curves of the left atrium and left ventricle were generated. Conduit volume was calculated and percentiles were established by the lambda-mu-sigma method of Cole and Green. Contributions of active, passive, and conduit volume to LV filling were measured and related to heart rate by linear regression. LV and LA peak filling rates (PFR) and peak emptying rates (PER) and time to PFR and PER normalized to the R-R interval (PFRConduit volume increased with body surface area. The contribution of LA active emptying to LV filling tended to increase with decreasing heart rate, while the contribution of passive emptying decreased. Conduit volume contributed most to LV filling (median, 57.58 %; interquartile range, 12.85%) with a tendency to increase with decreasing heart rate. Close diastolic AV coupling was demonstrated by virtually identical LV PFRAssessment of conduit volume and AV coupling by three-dimensional echocardiography is feasible in infants and children. The references of this study can serve as a basis to further investigate the role of parameters of AV coupling in pediatric patients with heart diseases concerning diastolic and LA function.

Robust biomarkers to predict response to immune checkpoint blockade (ICB) in metastatic urothelial carcinoma (mUC) are still in demand. Recently, early C-reactive protein (CRP) kinetics and especially the novel CRP flare-response phenomenon has been associated with immunotherapy response.We conducted a multicentre observational study comprising 154 patients with mUC treated with ICB to evaluate the predictive value of a previously described on-treatment CRP kinetics: CRP flare responders (at least doubling of baseline CRP within the first month after initiation of ICB followed by a decline below baseline within three months), CRP responders (decline in baseline CRP by ≥ 30% within three months without a prior flare) and the remaining patients as CRP non-responders. CRP kinetics groups were correlated with baseline parameters, PD-L1 status, progression-free survival (PFS) and overall survival (OS).Objective response was observed in 57.1% of CRP responders, 45.8% of CRP flare responders and 17.9% of CRP non-responders (P 0.001). CRP flare response was associated with prolonged PFS and OS (P 0.001). In multivariable Cox regression analysis, CRP flare responders showed a risk reduction of ∼70% for tumour progression and death compared to CRP non-responders. Subgroup analysis of CRP flare responders revealed that patients with a long-flare response (completed flare-response kinetics ≥6 weeks on-treatment) showed even more favourable outcomes following ICB (HR = 0.18, 95%-CI: 0.07-0.48, P 0.001).CRP (flare)response robustly predicts immunotherapy response and outcomes in mUC independent of PD-L1 status. Thus, early on-treatment CRP kinetics is a promising low-cost and easy-to-implement biomarker to optimise therapy monitoring in patients with mUC treated with ICB.

Background Evaluation of left atrial (LA) size and function is important in congenital and acquired pediatric cardiac disease. Real-time three-dimensional echocardiography (3DE) offers noninvasive assessment of cardiac volumes and phasic function independent of geometric assumptions. The aim of this prospective multicenter study was to establish pediatric reference values for LA 3DE volumes and phasic function based on a large cohort of healthy children. Methods LA data sets of 432 subjects (0 days-222 months) were analyzed prospectively using a vendor-independent software. LA volumes (maximal [Vmax], minimal [Vmin], and before atrial contraction) as well as phasic function (active and passive emptying fraction [EF]) were assessed. For volumes, sex-specific reference values, percentiles, and z-scores were calculated by the LMS method of Cole and Green. Results Absolute volumes increased with age and body surface area. Active EF and relative duration of atrial emptying tended to increase with increasing R-R intervals, while passive EF decreased. Reproducibility of volumes was very good (intra- and interobserver variability for Vmax and Vmin (mean bias ± SD, 0.1 ± 0.9 mL and 0.7 ± 2.8 mL). Volumes were well correlated with cardiac magnetic resonance measurements showing known underestimation of volumes by 3DE (mean bias ± SD, Vmax –14.2 ± 14 mL; Vmin –11.5 ± 10 mL). Conclusions Pediatric LA volumes and phasic function indices were reproducibly measured by 3DE. The provided pediatric reference values can be the basis for evaluation of the LA by 3DE and contribute to detection of LA dysfunction and follow-up of patients with congenital heart diseases.