Abstract 19165: Regional Changes in Cellular and Molecular Pathology in Children With End-stage Dilated Cardiomyopathy: Correlation With Cardiac Performance
Bibliographic record
Abstract
Dilated cardiomyopathy (DCM) carries poor prognosis in children, often needing heart transplant. Regional differences in left ventricular (LV) function suggest inhomogeneous expression of contractility related proteins. However, associations between myocardial performance and histological / molecular findings are poorly defined. We sought to investigate associations of regional myocardial performance with histological and molecular changes in hearts explanted from children with DCM, undergoing transplantation. Clinical and echo features (including tissue Doppler and strain) were correlated with histological and molecular findings in hearts explanted from 9 children [median age 2.8 years (range 4.4 months-17 years); 6 had LVAD]. Interstitial fibrosis, myocyte volume, and expression of proteins (western blot) implicated in fibrosis and function ( p38 , ERK , phospho- JNK , phospho- GSK , SMA , myosin heavy chain, cadherin, ILK , sarcoplasmic reticulum Ca 2+ -ATPase [SERCA2a], phospho- CamKII , phospholamban [PLN], and phospho-PLN) were correlated with speckle tracking strain from 11 regions per patient (basal and mid regions of anterior septum, anterior, lateral, posterior and inferior LV segments, and right ventricular [RV] free wall). On average, no significant difference was noted for the percentage of fibrosis and myocyte volume between the various LV segments, and between RV and LV. LV dimension, systolic and diastolic function were not related to interstitial fibrosis, myocyte volume or molecular signaling. Tricuspid annular plane systolic excursion was related to myocyte volume (r=0.89; p <0.01). An inverse relationship between the extent of interstitial fibrosis and segmental longitudinal strain was present for LV basal and mid posterior segments (basal posterior, r=0.96, p <0.01; mid posterior, r=0.74, p =0.05). Global longitudinal strain was related to expression of ILK and SERCA2a (ILK, r=0.78, p =0.02; SERCA2a, r=0.71, p =0.04). This study demonstrated association of regional cardiac function in children with DCM with expression of calcium-cycling and contractile proteins, as well as interstitial fibrosis. These findings have implications for diagnosis and therapeutic targets in pediatric DCM.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".