Inflammation and acute cardiotoxicity in adult hematological patients treated with CAR-T cells: results from a pilot proof-of-concept study.

AIMS: Chimeric Antigen Receptor-T (CAR-T) cell infusion is a rapidly evolving antitumor therapy; however, cardiovascular (CV) complications, likely associated with cytokine release syndrome (CRS) and systemic inflammation, have been reported to occur. The CARdio-Tox study aimed at elucidating incidence and determinants of cardiotoxicity related to CAR-T cell therapy. METHODS: Patients with blood malignancies candidate to CAR-T cells were prospectively evaluated by echocardiography at baseline and 7 and 30 days after infusion. The study endpoints were i) incidence of cancer therapy-related cardiac dysfunction (CTRCD), CTRCD were also balanced for any grade CRS, but CTRCD occurred of Cardiology Guidelines on Cardio-Oncology (decrements of left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS) and/or elevations of cardiac biomarkers (high sensitivity troponin I, natriuretic peptides) and ii), correlations of echocardiographic metrics with inflammatory biomarkers. RESULTS: Incidence of CTRCD was high at 7 days (59,3%), particularly in subjects with CRS. The integrated definition of CTRCD allowed the identification of the majority of cases (50%). Moreover, early LVEF and GLS decrements were inversely correlated with fibrinogen and interleukin-2 receptor levels (p always ≤ 0.01). CONCLUSIONS: There is a high incidence of early CTRCD in patients treated with CAR-T cells, and a link between CTRCD and inflammation can be demonstrated. Dedicated patient monitoring protocols are advised.

Cost-utility of cardiac contractility modulation in patients with heart failure with reduced ejection fraction in Italy.

AIMS: Cardiac contractility modulation (CCM) is a device therapy for heart failure, based on the delivery of high-voltage biphasic impulses to the right ventricular septum during the myocardial absolute refractory period. This study evaluated the cost-effectiveness of CCM therapy plus optimal medical therapy (OMT) vs. OMT alone in patients with heart failure with reduced ejection fraction. METHODS AND RESULTS: A Markov model with a lifespan time horizon was developed to assess the cost-utility using the FIX trials as main data sources. A deterministic sensitivity analysis and a probabilistic sensitivity analysis were run to analyse the decision uncertainty in the model through cost-effectiveness acceptability curve (CEAC) and cost-effectiveness acceptability frontier (CEAF). Value of information analysis was also conducted computing the expected value of perfect information (EVPI) and the expected value of partial perfect information. The base case results showed that the CCM plus OMT option was highly cost-effective compared with OMT alone with an incremental cost-utility ratio of €7034/quality-adjusted life year (QALY). The CEAC and CEAF illustrated that for all willingness to pay levels above €5600/QALY, tested up to €50 000/QALY, CCM plus OMT alternative had the highest probability of being cost-effective. The EVPI per patient was estimated to be €124 412 on a willingness to pay threshold of €30 000/QALY. CONCLUSIONS: For patients with heart failure with reduced ejection fraction, CCM therapy could be cost-effective when taking a lifetime horizon. Further long-term, post-approval clinical studies are needed to verify these results in a real-world context, particularly concerning the effect of CCM therapy on mortality.

Obstructive sleep apnea in sarcoidosis and impact of cpap treatment on fatigue.

RATIONALE: An increased incidence of Obstructive Sleep Apnea (OSA) in sarcoidosis has been described in small sample size studies. Fatigue is common in sarcoidosis and OSA could be a relevant, treatable comorbidity. To date, the effect of Continuous Positive Airway Pressure (CPAP) on fatigue has never been assessed. OBJECTIVES: To investigate the prevalence of OSA in sarcoidosis, fatigue status and daytime sleepiness in patients of our center. To explore the effect of CPAP in fatigue and daytime sleepiness after 3 months using validated questionnaires. METHOD: Single group, one center, open-label prospective cohort study. MEASUREMENTS AND MAIN RESULT: We enrolled 68 patients and OSA was diagnosed in 60 (88.2%): 25 (36.8%) were mild while 35 (51.5%) were moderate-to-severe. 38 (55.9%) patients received CPAP but only 20 (30.9%) were compliant at 3-month evaluation. Questionnaires demonstrated fatigue in 34 (50%) and daytime sleepiness in 21 (30.9%). In multivariate regression analysis, Scadding stage and FAS behave as predictors of Apnea-Hypopnea Index (AHI) severity while sleepiness and steroids weren't associated. FAS score (ΔFAS = 6.3; p = 0.001) and ESS score (ΔESS = 2.8; p = 0.005) improved after three months of CPAP. CONCLUSIONS: OSA is highly prevalent in patients affected by sarcoidosis. ESS questionnaire is not reliable for OSA screening and other pre-test probability tool should be evaluated in further studies. CPAP leads to a significative reduction of fatigue and daytime sleepiness at three-month. Further studies are needed to confirm the high prevalence of OSA in sarcoidosis and the positive role of CPAP in fatigue. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (2): 169-178).