Cardiac Myosin Inhibition in Heart Failure With Normal and Supranormal Ejection Fraction
Notice bibliographique
Résumé
Importance: Patients with heart failure with preserved ejection fraction (HFpEF) who have left ventricular ejection fraction (LVEF) of 60% or greater have limited treatment options. Objective: To examine the effects of cardiac myosin inhibition with mavacamten in patients with HFpEF with LVEF of 60% or greater. Design, Setting, and Participants: The EMBARK-HFpEF trial was a phase 2a, open-label, single-arm, multicenter trial conducted from November 6, 2020, to February 26, 2024, at 20 sites in the US and Canada. Patients with symptomatic HFpEF (defined as a New York Heart Association [NYHA] functional class II or III), LVEF of 60% or greater, elevated N-terminal pro-B-type natriuretic peptide (NTproBNP), and left ventricular hypertrophy were eligible for inclusion. Intervention: Mavacamten treatment for 26 weeks, starting at 2.5 mg and potentially titrated up to 5 mg at week 14 based on prespecified LVEF and NTproBNP criteria. Main Outcomes and Measures: Primary efficacy end points (measured as the change from baseline to week 26) included NTproBNP and high-sensitivity troponin T (hsTnT); additional efficacy end points included changes in high-sensitivity troponin I (hsTnI), NYHA functional class, and echocardiographic parameters (resting and peak exercise). Safety end points included treatment-emergent adverse events and reductions in LVEF to less than 30%. Results: A total of 30 patients were enrolled and treated with mavacamten. Median (IQR) patient age was 76 (70-80) years, and 16 patients (53.3%) were female. From baseline to week 26, mavacamten was associated with reductions in NTproBNP (mean reduction, -26%; 95% CI, -44% to -4%; P = .04), hsTnT (mean reduction, -13%; 95% CI, -23% to -3%; P = .02), and hsTnI (mean reduction, -20%; 95% CI, -32% to -6%; P = .01). Cardiac biomarker values returned toward baseline levels 8 weeks after drug discontinuation. NYHA class improved in 10 of 24 patients (41.7%) who had evaluable NYHA class data at the end of treatment, and improvements in echocardiographic markers of LV diastolic function were observed. Mean LVEF decreased by 3.2 absolute percentage points (95% CI, 1.1-5.4; P = .005) during treatment. Mavacamten was interrupted in 3 patients (10% of the study population; 95% CI, 2.1%-26.5%) due to protocol prespecified criteria of LVEF less than 50% (n = 2) or a more than 20% relative decrease from baseline (n = 1; nadir LVEF, 58%), with LVEF recovery observed in all 3 patients. There were no deaths or instances of LVEF less than 30%; 1 patient had worsening heart failure deemed unrelated to the study drug. Conclusions and Relevance: In an open-label trial in patients with HFpEF with LVEF of 60% or greater, mavacamten was associated with improvements in biomarkers of cardiac wall stress and injury, with no sustained reductions in LVEF observed. Trial Registration: ClinicalTrials.gov Identifier: NCT04766892.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 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) | 0,000 | 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 tête enseignante, 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 ».