Citations

Abstract Aims Aortic valve-sparing root replacement is recommended over composite root replacement for aortic root aneurysms, especially in younger patients, but long-term outcomes in low-volume nationwide settings remain unclear. The objectives are to compare long-term survival, stroke, and reoperation rates between the two procedures in a low-volume national setting. Methods and results Patients were identified from the Western Danish Heart Registry and the Danish Heart Registry. Cases were validated by review of operative descriptions. The primary outcome was long-term survival from all-cause mortality; secondary outcomes included stroke, reoperation, recurrent aortic regurgitation, and aortic stenosis. Groups were balanced using propensity score matching. Echocardiographic data were provided for the matched cohort. We identified 760 patients treated with composite root replacement and 179 patients with aortic valve-sparing root replacement between January 2010 and April 2022. Mean follow-up was 6.5 years. Composite root replacement patients were younger [50.7 years (SD 14.1) vs. 55.2 (SD 13.5), P < 0.001], but more comorbid with a median EuroSCOREII of 5.5 [interquartile range (IQR): 3.3–11.7] vs. 3.4 (IQR: 2.6–5.0) (P < 0.001). After matching 157 patients per group, aortic valve-sparing root replacement showed improved 10-year survival [91.2%, 95% confidence interval (CI) 82.3–95.8 vs. 80.4%, 95% CI 70.0–87.5, log-rank P = 0.026], with lower 10-year stroke risk (4.9%, 95% CI 1.8–13.0 vs. 18.9%, 95% CI 11.7–29.9, log-rank P = 0.007). Risk of reoperation was nonsignificant (log-rank P = 0.12), which was consistent in the crude population when accounting for competing risk of death (log-rank P = 0.09). Conclusion In this nationwide study, aortic valve-sparing root replacement was associated with better long-term survival and lower stroke risk, supporting its role as a durable surgical option for selected patients.

Key Points Automated cyst segmentation in autosomal dominant polycystic kidney disease could transform care by enabling precise monitoring of cyst progression with minimal manual effort. This technology can facilitate more consistent assessments of cyst burden across patients. Translating these segmentation models from magnetic resonance imaging to computed tomography is crucial for providing comprehensive, modality-independent evaluations. Background Total kidney and liver volumes are key image-based biomarkers to predict the severity of kidney and liver phenotype in autosomal dominant polycystic kidney disease (ADPKD). However, magnetic resonance (MR) imaging-based advanced biomarkers like total cyst number and cyst parenchyma surface area have been shown to more accurately assess cyst burden and improve the prediction of disease progression. The main aim of this study was to extend the calculation of advanced biomarkers to other imaging modalities; thus, we propose a fully automated model to segment kidney and liver cysts in computed tomography (CT) images. Methods Abdominal CTs of patients with ADPKD were gathered retrospectively between 2001 and 2018. A three-dimensional deep learning method using the nnU-Net architecture was trained to learn cyst edges-cores and the noncystic kidney/liver parenchyma. Separate segmentation models were trained for kidney cysts in contrast-enhanced CTs and liver cysts in noncontrast CTs using an active learning approach. Two experienced research fellows manually generated the reference standard segmentation, which were reviewed by an expert radiologist for accuracy. Results Two-hundred CT scans from 148 patients (mean age, 51.2±14.1 years; 48% male) were used for model training (80%) and testing (20%). In the test set, both models showed good agreement with the reference standard segmentations, similar to the agreement between two independent human readers (model versus reader: TCN kidney/liver r =0.96/0.97 and CPSA kidney r =0.98, inter-reader: TCN kidney/liver r =0.96/0.98 and CPSA kidney r =0.99). Conclusions Our study demonstrates that automated models can segment kidney and liver cysts accurately in CT scans of patients with ADPKD.

Key Points The growing knowledge of single-gene causes of pediatric-onset kidney diseases necessitates a structured application of genetic testing in practice. The clinical application of a combined nephrogenetics approach for management of kidney diseases is not well described in pediatric settings. Real-world application of a kidney genetics workflow highlights clinical value and challenges to be addressed for its successful implementation. Background The expanding knowledge of identifiable genetic contributions to pediatric inherited kidney diseases, and the increasing availability of genetic testing resources necessitates a combined nephrogenetics clinical approach. Although such models are described for adults, the effect of a structured nephrogenetics workflow on children with inherited kidney disease has not been rigorously evaluated. Methods Clinical and genetic data of patients aged younger than 1–21 years over a 10-year period between 2014 and 2024 from a single-center pediatric inherited kidney disease outpatient program were evaluated. Genetic variants were classified as pathogenic/likely pathogenic and variants of uncertain significance (VUS). Patients were grouped into “informative” or “uninformative” groups based on the effect of genetic test results on disease management and outcomes. Results Of the N =356 patients evaluated for a known or suspected inherited kidney disease, N =188 received clinical genetic testing. Of these, N =147 had an “informative” genetic test affecting at least one positive clinical outcome. Patients with an “informative” genetic test mostly harbored a pathogenic/likely pathogenic variant ( N =122). An additional N =25 had a VUS reclassified as a “VUS-of-interest” affecting a positive outcome measure. Genetic test results led to change in clinical diagnosis (reverse phenotyping, 46%), informed specific diagnosis-based treatment (46%), avoided unnecessary immunosuppression (27%) or kidney biopsy (18%), and guided extrarenal evaluation (72%) in patients with an informative test. Patients with a glomerular (odds ratio [OR]=5.23; 95% confidence interval [CI], 1.96 to 13.96) or a tubular functional disease (OR=2.17; 95% CI, 1.31 to 5.59) were more likely and those with a structural kidney disease (OR=0.39; 95% CI, 0.25 to 0.60) were less likely to receive a genetic test when compared with all other disease categories combined. Conclusions This workflow integrated multidisciplinary care for children with inherited kidney disease and describes a model for actionable clinical care plans after genetic testing. Informative genetic tests were associated with positive outcomes, and notable challenges include access to combined nephrology and genetics expertise for informed testing and an effective result return including VUS interpretation.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

ABSTRACT Background This study aims to assess how Watchman FLX (Boston Scientific) and Amplatzer Amulet (Abbott) devices for left atrial appendage occlusion (LAAO) impact the flow dynamics in the LA and the risk of device‐related thrombosis (DRT). Methods Flow simulations were carried out for 12 AF patients before and after undergoing LAAO. Six patients had Watchman FLX while the other six had Amulet devices, of which three in each group had DRT. The flow parameters investigated included the LA velocities, pressure, time averaged wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). Low TAWSS and high OSI and RRT are generally associated with flow stasis and thrombosis. Results LA flow dynamics differed significantly between the two groups. On average, after LAAO, the Amulet patients exhibited a 25% increase in TAWSS and 24% decrease in RRT while the Watchman FLX patients exhibited, on average, a 24% decrease in TAWSS and a 23% increase in RRT. Both populations experienced an increase in LA pressure (~10% for Amulet patients and 16% for Watchman FLX patients). Increased DRT volume seems to be correlated with low TAWSS and elevated RRT. Conclusion This preliminary study suggests that the Amulet device might be associated with improved LA flow dynamics and a potentially lower incidence of DRT compared with the Watchman. However, a larger clinical study is needed to confirm these findings.

Abstract Background Cardiac troponin (cTn) levels exceeding the 99th percentile upper reference limit and a rise/fall pattern are key for diagnosing myocardial injury and infarction. Macrotroponins, formed by patient anti-cTn antibodies targeting cTn, can cause persistently elevated cTn levels without ongoing myocardial injury. The frequency and impact of macrotroponin interference on cTn 99th percentiles are unclear. This study compares sex-specific 99th percentiles for 2 cTn assays, before and after excluding macrotroponin-positive samples, focusing on the top 10% of cTn levels. Methods We examined 1058 plasma samples from healthy individuals previously used for Danish cTn 99th percentiles. Following International Federation of Clinical Chemistry and Laboratory Medicine educational recommendations, macrotroponin presence was assessed in the top 10% cTn samples using immunoglobulin G (IgG) depletion screening and a reference sucrose gradient, confirming macrotroponin when both methods concurred. Due to analytical dilution constraints, [the highest] 88 of 135 Siemens Atellica high-sensitivity cTnI (hs-cTnI) samples were analyzed with both methods. All 106 Roche hs-cTnT samples were negative using IgG depletion, and sucrose analysis was limited to the highest 70 samples. Results Macrotroponin was found in 76% (67/88) of Siemens samples but in none of the Roche samples (0/70). Excluding macrotroponin-affected samples lowered the Siemens 99th percentiles from 117 ng/L to 22 ng/L in men and from 37 ng/L to 9 ng/L in women. The 99th/50th percentile ratio for Siemens decreased from 12- to 29-fold to 3- to 7-fold, approaching the Roche ratios. Conclusions Macrotroponin significantly influenced the Siemens Atellica hs-cTnI 99th percentiles, suggesting important clinical implications that warrant further prospective studies. The 99th/50th percentile ratio may help evaluate macrotroponin interference in troponin assays.

Abstract Aims In aortic stenosis (AS), estimation of left ventricular (LV) contractility is difficult as most markers of systolic LV function are load-dependent. The ratio of LV ejection fraction (LVEF) to end-systolic wall stress (ESWS), has been widely accepted as a marker of contractility. However, no studies have evaluated if this ratio is affected by loading conditions. The study describes changes in ESWS and ESWS corrected LVEF after transcatheter aortic valve replacement (TAVR). Methods and results In this prospective study, 41 patients with severe AS underwent echocardiography, LV catheterisation, and computed tomography (CT) before and immediately after TAVR. ESWS was estimated from echocardiography alone (ESWSEcho), combining CT LV dimensions and echocardiographic gradients (ESWSCT + echo) and combining CT LV dimensions and invasively measured LV end-systolic pressure (ESWSCT + Invasive). ESWSecho, ESWSCT + echo and ESWSCT + Invasive all decreased significantly after TAVR (89 ± 48 vs. 57 ± 37 Kdynes/cm2, P < 0.01; 69 ± 8 vs. 51 ± 8 Kdynes/cm2, P < 0.01, and 197 ± 69 vs. 137 ± 48 Kpa/cm2, P < 0.01, respectively). We observed weak to moderate associations between the methods. After TAVR, LVEF corrected to ESWSecho, ESWSCT + echo and ESWSCT + Invasive increased (0.93 ± 0.07 vs. 1.91 ± 2.1, P = 0.013; 0.36 ± 0.19 vs. 0.58 ± 0.33, P < 0.01, and 0.3 ± 0.02 vs. 2.5 ± 1.5, P < 0.01, respectively). Conclusion ESWSecho, ESWSCT + echo and ESWSCT + Invasive decreased significantly after TAVR suggesting they reflect afterload, but independent of method, ESWS corrected LVEF increased slightly post-TAVR, indicating load dependency.