Contexte La tomographie par émission de positons (TEP) au 18F-florbetaben permet de détecter l’amylose cardiaque (AC), en particulier les formes AL (chaînes légères), ainsi que les sites d’infiltrats amyloïdes AL extra-cardiaques. Objectifs Identifier l’AC et différencier les formes AL-AC et ATTR-AC (transthyrétine) en évaluant l’atteinte cardiaque et multiorganique par TEP corps entier au 18F-florbetaben. Méthodes Étude multicentrique incluant 61 patients présentant une hypertrophie ventriculaire gauche liée à une AL-AC (n=25), une ATTR-AC (n=25) ou un rétrécissement aortique (n=11, témoins). Une TEP corps entier de 20minutes était précédée d’un enregistrement cardiaque dynamique de 10minutes débutant à l’injection du 18F-florbetaben. Résultats La fixation du traceur était significativement plus élevée chez les patients AC que chez les témoins. Les patients AL-AC présentaient une captation accrue au niveau du myocarde, des poumons et de la rate, et diminuée dans le sang, les glandes salivaires, les muscles squelettiques et le foie. Parmi les paramètres cardiaques, le rapport SUVmax ventricule gauche/sang issu de la TEP corps entier discriminait le mieux l’AL-AC de l’ATTR-AC, identifiant correctement 90 % (55/61) des patients (κ=0,819±0,064), avec des seuils de SUVmax de 2–4 pour l’ATTR-AC et>4 pour l’AL-AC. En combinant les paramètres cardiaques et extra-cardiaques, les prédicteurs multivariés les plus pertinents étaient le volume de captation myocardique (MUV) et les SUVmean pulmonaires et salivaires. Des seuils de MUV>10mL pour l’AC et de SUVmean poumon/glandes salivaires>0,285 pour l’AL-AC permettaient d’identifier correctement 93 % (57/61) des patients (κ=0,871±0,056). Le MUV améliorait la performance du score de Perugini sur la scintigraphie osseuse pour l’AL-AC et l’ATTR-AC (p<0,001). Conclusion La TEP corps entier au 18F-florbetaben permet d’identifier l’amylose cardiaque et de distinguer les formes AL et ATTR. L’évaluation conjointe de l’atteinte cardiaque et multiorganique renforce la précision diagnostique.
ABSTRACT:The phase 2 ALYCANTE trial aimed to evaluate the investigator-assessed complete metabolic response at 3 months from the axicabtagene ciloleucel (axi-cel) infusion as a primary end point in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation (ASCT). This study showed a significant improvement in complete metabolic response rate at 3 months based on historical controls. This study reports the health-related quality of life (HRQoL) results as a secondary end point. HRQoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) cancer-specific questionnaire, the Quality of Life Questionnaire high-grade non-Hodgkin lymphoma 29 (QLQ-NHL-HG29) , and the EuroQol Quality of Life Scale-5 dimensions-5 levels of severity (EQ-5D-5L) generic questionnaire at baseline and 1, 3, 6, and 12 months after axi-cel infusion. Among the 62 patients included, 60 (97%) completed a baseline and at least 1 postbaseline HRQoL assessment. At 1 month infusion, adjusted mean change in HRQoL scores from baseline showed a clinically significant deterioration (greater than the clinical threshold) in physical, role, social functioning, and fatigue. However, all HRQoL dimensions recovered by 3 months after infusion and remained stable or continued to improve by 12 months. In an exploratory analysis, adjusted mean change in HRQoL score from baseline in ALYCANTE was similar to or better than in ASCT-eligible patients who received axi-cel in the phase 3 ZUMA-7 trial. Finally, the global health status and fatigue scores of the ALYCANTE population improved to levels comparable to the general French population of similar age by 3 months after infusion. These findings indicate that axi-cel improves HRQoL regardless of transplant eligibility, supporting its use across a broad patient population. This trial was registered at www.clinicaltrials.gov as #NCT04531046.
Introduction Recent guidelines have proposed dichotomizing acute heart failure and cardiogenic shock (CS) phenotypes based on the presence of signs/symptoms of hypoperfusion/congestion. Objective We aim to assess the clinical impact of congestion on prognosis in unselected CS. Method FRENSHOCK is a prospective registry including 772 CS patients from 49 centres. Patients were classified as cold and wet or cold and dry according to congestive signs. Mortality at 30 days was analysed according to baseline phenotype. Results Among 593 CS patients with available pertinent data, 70.7% were male, with a median age of 67.0 (58.0–77.0) years, and 521 (87.9%) presented with congestion. Congestive patients had higher rates of prior cardiac disease (60.5% vs. 43.1%, P<0.01) and chronic kidney disease (24.2% vs. 12.5%, P=0.04). No differences were found regarding SCAI distribution and lactate levels. Congestion was associated with a significant increase in 30-day all-cause mortality (HR 1.99; 95% CI 1.05–3.78; P=0.04), particularly among patients with persistent congestion after 24hours of care (HR 2.29; 95% CI 1.20–4.36; P=0.01) (Fig. 1). Conversely, patients with resolved congestion at 24hours had similar outcomes when compared to non-congestive patients (HR 0.76; 95% CI 0.31–1.88; P=0.56). The detrimental impact of congestion was corroborated in a multivariate Cox regression analysis adjusted for baseline characteristics. Conclusion Congestion and its persistence beyond 24hours of management are frequent in patients with CS and are significantly associated with increased 30-day all-cause mortality. Further studies are warranted to clarify optimal strategies decongestion in CS patients.
Sickle cell disease is a hereditary haemoglobinopathy characterized by chronic haemolysis, vaso-occlusive events and multisystem involvement. Whereas haematological and pulmonary complications are well recognized, cardiac involvement - particularly arrhythmias - has recently emerged as an important contributor to morbidity and mortality. This review examines the spectrum of rhythm disturbances in this population based on recent clinical data. Electrocardiographic abnormalities are common, including corrected QT interval prolongation, sinus tachycardia and repolarization changes. Supraventricular and ventricular arrhythmias are increasingly reported, and may contribute to sudden cardiac death, particularly during acute vaso-occlusive events. Proposed mechanisms are multifactorial, involving myocardial ischaemia imbalance and inflammation. Despite growing awareness, the prognostic significance and optimal management of arrhythmias in sickle cell disease remain poorly defined. Further studies are needed to improve risk stratification and guide targeted preventive and therapeutic strategies.
Introduction Despite recent advances, the prognosis of transthyretin (TTR) cardiac amyloidosis remains poor, largely due to late diagnosis, when irreversible complications have developed. Diagnosis still relies mainly on peripheral tissue or heart biopsy, and quantification of circulating TTR or any other plasmatic marker is of no help. Extracellular vesicles (EVs) are mediators of intercellular communication. Plasma EVs can convey crucial information about diseased tissue. Yet, to date, the protein cargo of plasma EVs has never been studied in TTR amyloid (ATTR) cardiomyopathy. Objective Our goal was to quantify the proteome of plasma EVs of ATTR cardiomyopathy to define new markers that may help in understanding lesion pathophysiology, prognostic assessment and/or diagnosis. Method Through a differential label-free mass-spectrometry-based proteomic approach, we investigated the plasma EV proteome of 65 patients with hypertrophic cardiomyopathy, caused by TTR amyloidosis (ATTR+, n=41) or resulting from non-amyloid cardiac disease (ATTR–, n=24). Results A specific signature including 117 deregulated proteins was found in ATTR+ patients. ATTR+ EVs were enriched in proteins from several pathways involved in vascular homeostasis, coagulation and inflammation. Most importantly, TTR and plasminogen were upregulated in TTR+ EVs, whereas α2-antiplasmin was down-regulated. This is highly relevant as plasmin (the active form of plasminogen), whose main physiologic inhibitor is α2-antiplasmin, has been previously shown to initiate the amyloidogenic process through TTR cleavage. Conclusion Our study revealed new insights into the pathophysiology of ATTR cardiomyopathy with potential for the future development of diagnostic biomarkers and therapeutic targets.
