1.
Empagliflozin Effects on Pulmonary Artery Pressure in Patients With Heart Failure: Results From the EMBRACE-HF Trial.
Nassif, ME, Qintar, M, Windsor, SL, Jermyn, R, Shavelle, DM, Tang, F, Lamba, S, Bhatt, K, Brush, J, Civitello, A, et al
Circulation. 2021;(17):1673-1686
-
-
Free full text
-
Abstract
BACKGROUND Sodium glucose cotransporter 2 inhibitors (SGLT2 inhibitors) prevent heart failure (HF) hospitalizations in patients with type 2 diabetes and improve outcomes in those with HF and reduced ejection fraction, regardless of type 2 diabetes. Mechanisms of HF benefits remain unclear, and the effects of SGLT2 inhibitor on hemodynamics (filling pressures) are not known. The EMBRACE-HF trial (Empagliflozin Evaluation by Measuring Impact on Hemodynamics in Patients With Heart Failure) was designed to address this knowledge gap. METHODS EMBRACE-HF is an investigator-initiated, randomized, multicenter, double-blind, placebo-controlled trial. From July 2017 to November 2019, patients with HF (regardless of ejection fraction, with or without type 2 diabetes) and previously implanted pulmonary artery (PA) pressure sensor (CardioMEMS) were randomized across 10 US centers to empagliflozin 10 mg daily or placebo and treated for 12 weeks. The primary end point was change in PA diastolic pressure (PADP) from baseline to end of treatment (average PADP weeks 8-12). Secondary end points included health status (Kansas City Cardiomyopathy Questionnaire score), natriuretic peptides, and 6-min walking distance. RESULTS Overall, 93 patients were screened, and 65 were randomized (33 to empagliflozin, 32 to placebo). The mean age was 66 years; 63% were male; 52% had type 2 diabetes; 54% were in New York Heart Association class III/IV; mean ejection fraction was 44%; median NT-proBNP (N-terminal pro B-type natriuretic peptide) was 637 pg/mL; and mean PADP was 22 mm Hg. Empagliflozin significantly reduced PADP, with effects that began at week 1 and amplified over time; average PADP (weeks 8-12) was 1.5 mm Hg lower (95% CI, 0.2-2.8; P=0.02); and at week 12, PADP was 1.7 mm Hg lower (95% CI, 0.3-3.2; P=0.02) with empagliflozin versus placebo. Results were consistent for PA systolic and PA mean pressures. There was no difference in mean loop diuretic management (daily furosemide equivalents) between treatment groups. No significant differences between treatment groups were observed in Kansas City Cardiomyopathy Questionnaire scores, natriuretic peptide levels, and 6-min walking distance. CONCLUSIONS In patients with HF and CardioMEMS PA pressure sensor, empagliflozin produced rapid reductions in PA pressures that were amplified over time and appeared to be independent of loop diuretic management. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03030222.
2.
Effect of Vein-First vs Artery-First Surgical Technique on Circulating Tumor Cells and Survival in Patients With Non-Small Cell Lung Cancer: A Randomized Clinical Trial and Registry-Based Propensity Score Matching Analysis.
Wei, S, Guo, C, He, J, Tan, Q, Mei, J, Yang, Z, Liu, C, Pu, Q, Ma, L, Yuan, Y, et al
JAMA surgery. 2019;(7):e190972
-
-
Free full text
-
Abstract
IMPORTANCE It is important to develop a surgical technique to reduce dissemination of tumor cells into the blood during surgery. OBJECTIVE To compare the outcomes of different sequences of vessel ligation during surgery on the dissemination of tumor cells and survival in patients with non-small cell lung cancer. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized clinical trial was conducted from December 2016 to March 2018 with patients with non-small cell lung cancer who received thoracoscopic lobectomy in West China Hospital, Daping Hospital, and Sichuan Cancer Hospital. To further compare survival outcomes of the 2 procedures, we reviewed the Western China Lung Cancer database (2005-2017) using the same inclusion criteria. INTERVENTIONS Vein-first procedure vs artery-first procedure. MAIN OUTCOMES AND MEASURES Changes in folate receptor-positive circulating tumor cells (FR+CTCs) after surgery and 5-year overall, disease-free, and lung cancer-specific survival. RESULTS A total of 86 individuals were randomized; 22 patients (25.6%) were younger and 64 (74.4%) older than 60 years. Of these, 78 patients were analyzed. After surgery, an incremental change in FR+CTCs was observed in 26 of 40 patients (65.0%) in the artery-first group and 12 of 38 (31.6%) in the vein-first group (P = .003) (median change, 0.73 [interquartile range (IQR), -0.86 to 1.58] FU per 3 mL vs -0.50 [IQR, -2.53 to 0.79] FU per 3 mL; P = .006). Multivariate analysis confirmed that the artery-first procedure was a risk factor for FR+CTC increase during surgery (hazard ratio [HR], 4.03 [95% CI, 1.53-10.63]; P = .005). The propensity-matched analysis included 420 patients (210 with vein-first procedures and 210 with artery-first procedures). The vein-first group had significantly better outcomes than the artery-first group for 5-year overall survival (73.6% [95% CI, 64.4%-82.8%] vs 57.6% [95% CI, 48.4%-66.8%]; P = .002), disease-free survival (63.6% [95% CI, 55.4%-73.8%] vs 48.4% [95% CI, 40.0%-56.8%]; P = .001), and lung cancer-specific survival (76.4% [95% CI, 67.6%-85.2%] vs 59.9% [95% CI, 50.5%-69.3%]; P = .002). Multivariate analyses revealed that the artery-first procedure was a prognostic factor of poorer 5-year overall survival (HR, 1.65 [95% CI, 1.07-2.56]; P = .03), disease-free survival (HR, 1.43 [95% CI, 1.01-2.04]; P = .05) and lung cancer-specific survival (HR = 1.65 [95% CI, 1.04-2.61]; P = .03). CONCLUSIONS AND RELEVANCE Ligating effluent veins first during surgery may reduce tumor cell dissemination and improve survival outcomes in patients with non-small cell lung cancer. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03436329.