Cardiopulmonary and Laboratory Profiling of Patients with Thalassemia At Risk for Pulmonary Hypertension: Report From the Thalassemia Clinical Research Network.
Notice bibliographique
Résumé
Abstract Abstract 2122 Introduction: Pulmonary hypertension (PH) commonly develops in thalassemia syndromes, but is poorly characterized. Since limited data are available we set out to provide a comprehensive description of the cardiopulmonary and biological profile of patients with thalassemia at-risk for PH. Methods: We designed a case-control study of thalassemia patients at-risk for PH, defined by a tricuspid-regurgitant-jet velocity (TRV)≥2.5m/s on Doppler-echocardiography (echo) compared to those with low PH-risk, define by a TRV<2.5m/s, similar in age, gender, ethnicity and transfusion dependence. A single cross-sectional measurement for variables reflecting cardiopulmonary status and biological pathophysiology were obtained, including echo, 6-minute-walk-test (6MWT), Borg Dyspnea Score, New York Heart Association (NYHA) functional class, cardiac MRI, pulmonary function testing, laboratory analyses and biomarkers of hemolysis, inflammation, coagulation and adhesion, compared in thalassemia patients at high vs. low PH-risk. Results: Twenty-seven thalassemia patients with a mean TRV=2.5±0.6m/s (range:1.0–4.9m/s) were evaluated, 14 with a TRV≥2.5m/s. Mean age was 35±12 years, 70% were male, 74% were splenectomized, and 67% had thalassemia major (TM). Patients with PH-risk (mean TRV=3.1±0.7m/s) had a significantly higher frequency of splenectomy (OR:11.1 [95% CI: 1.11–112.0], p=0.04), higher NYHA functional class, Borg Dyspnea Score after 6MWT, and significantly larger right atrial size, left atrial volume, and left septal-wall thickness on echo and/or MRI, with elevated biomarkers of coagulation abnormalities, lactate dehydrogenase (LDH) levels, arginase concentration (5.7±7 vs. 78.7±108 ng/ml, p=0.003) and arginase activity, and lower arginine-bioavailability compared to low-risk patients (mean TRV=2.1±0.4m/s). Arginase concentration and activity correlated significantly to several echo/MRI parameters of cardiovascular function including cardiac index (r=0.75, p<0.0001), in addition to white blood cell count, several adhesion biomarkers, global-arginine-bioavailability and biomarkers of hemolytic rate, including LDH, hemoglobin and bilirubin. Arginase activity, but not concentration, correlated strongly to brain natriuretic factor (r =0.45, p=0.03). Diffusion capacity for carbon monoxide (DLCO) was generally low in our cohort (mean % predicted: 68.2±16.3 (range 45–115), however other measurements of pulmonary function were within the normal range, and together with DLCO, did not differ significantly by TRV. No significant difference was found in 6MWT in cases vs. controls, however the 6MWT paradoxically trended higher in patients with a TRV≥2.5m/s and may not be an ideal PH biomarker in thalassemia. The 6MWT was significantly worse in TM patients compared to patients with thalassemia intermedia (460±106 vs. 539±66 m, p=0.05), despite similar TRVs, was a poor predictor of echo/MRI parameters, and paradoxically correlated to increased right atrial size (r =0.42, p=0.03). A strong correlation of 6MWT to DLCO (r =0.51, p=0.008) may indicate a pulmonary contribution to 6MWT in this cohort as an additional confounding factor. Conclusions: Thalassemia patients with a TRV≥2.5m/s have additional echo and MRI parameters suggestive of PH-risk. Dysregulation of the arginine metabolome and the consequences of excess plasma arginase are associated with cardiopulmonary complications in thalassemia and warrants further study. Disclosures: Taher: Novartis: Research Funding, Speakers Bureau.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».