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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
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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.
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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
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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.
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A prospective, randomized study of inhaled prostacyclin versus nitric oxide in patients with residual pulmonary hypertension after pulmonary endarterectomy.
Abe, S, Ishida, K, Masuda, M, Ueda, H, Kohno, H, Matsuura, K, Tamura, Y, Watanabe, M, Matsumiya, G
General thoracic and cardiovascular surgery. 2017;(3):153-159
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OBJECTIVES Pulmonary endarterectomy (PEA) is an effective treatment for chronic thromboembolic pulmonary hypertension (CTEPH), but postoperative residual hypertension leads to in-hospital mortality. Inhaled epoprostenol sodium (PGI2) and NO are administered for pulmonary hypertension after cardiothoracic surgery. This prospective study provides the first comparative evaluation of the effects of inhaled PGI2 and NO on pulmonary hemodynamics, systemic hemodynamics, and gas exchange in patients developing residual pulmonary hypertension after PEA. METHODS Thirteen patients were randomized to receive either NO (n = 6) or PGI2 (n = 7) inhalation when pulmonary hypertension persisted after weaning from cardiopulmonary bypass. Hemodynamic and respiratory variables were measured before inhalation of the agent (T0); 30 min (T1), 3 h (T2), and 6 h after inhalation (T3); and the next morning (T4). The NO dose was started at 20 ppm and gradually tapered until extubation, and PGI2 was administered at a dose of 10 ng kg-1 min-1. RESULTS In both groups, mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) significantly decreased over time until T4 (mean PAP: p < 0.0001; PVR: p = 0.003), while mean systemic arterial blood pressure significantly increased (p = 0.028). There were no significant between-group differences in patient characteristics, cardiac index, left atrial pressure, or ratio of arterial oxygen tension to fraction of inspired oxygen. There were no in-hospital deaths. CONCLUSIONS Both inhaled PGI2 and NO significantly reduced PAP and PVR without adverse effects on systemic hemodynamics in patients who developed residual pulmonary hypertension after PEA. Inhaled PGI2 can be offered as alternative treatment option for residual pulmonary hypertension.
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Reducing contrast medium volume and tube voltage in CT angiography of the pulmonary artery.
Mourits, MM, Nijhof, WH, van Leuken, MH, Jager, GJ, Rutten, MJ
Clinical radiology. 2016;(6):615.e7-615.e13
Abstract
AIM: To evaluate image quality after contrast medium (CM) and tube voltage reduction in computed tomography angiography (CTA) of the pulmonary artery. MATERIALS AND METHODS Thirty-three patients referred for CTA of the pulmonary artery for suspected pulmonary embolism were included. Patients were randomly assigned to Protocol I (100 ml of 350 mg iodine/ml iodinated CM; n=16) or Protocol II (50 ml of 350 mg iodine/ml iodinated CM; n=17). Dual-energy CT (80 kV and 140 kV) was performed in all patients. An averaged weighted series equivalent to a 120 kV image acquisition was reconstructed. The mean attenuation value of CM was measured at eight positions in the pulmonary trunk and pulmonary arteries. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated. Qualitative assessment of the vascular enhancement was performed independently by two experienced radiologists using a three-point scale. Mean attenuation values, image noise, CNR, and SNR of images with 50 ml CM and images with 100 ml CM were compared and mean attenuation values, image noise, CNR, and SNR in 80 kV images and 120 kV images were compared. For qualitative analysis, interobserver variability was analysed using Cohen's kappa statistics. RESULTS The mean attenuation values in Protocol I and Protocol II were not significantly different at 80 kV (634.6±168.3 versus 537.9±146.7 HU; p=0.088) and 120 kV (482.8±127.7 versus 410.4±106.0 HU; p=0.085). The mean attenuation value at 80 kV was significantly higher than the mean attenuation value at 120 kV in Protocols I and II (p<0.001). The CNR and SNR were higher at 120 kV than at 80 kV in both protocols (p=0.000-0.019); however, there were no significant differences in the CNR and SNR between both protocols (p=0.600-0.952). Qualitative (subjective) analysis showed no statistical significant difference between Protocols I and II (p=0.524-1.000). CONCLUSION Low tube voltage (80 kV) CTA using 50 ml CM is not inferior to CTA at 120 kV using 100 ml CM.
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Prospective randomised comparison of diagnostic confidence and image quality with normal-dose and low-dose CT pulmonary angiography at various body weights.
Szucs-Farkas, Z, Megyeri, B, Christe, A, Vock, P, Heverhagen, JT, Schindera, ST
European radiology. 2014;(8):1868-77
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OBJECTIVES To find a threshold body weight (BW) below 100 kg above which computed tomography pulmonary angiography (CTPA) using reduced radiation and a reduced contrast material (CM) dose provides significantly impaired quality and diagnostic confidence compared with standard-dose CTPA. METHODS In this prospectively randomised study of 501 patients with suspected pulmonary embolism and BW <100 kg, 246 were allocated into the low-dose group (80 kVp, 75 ml CM) and 255 into the normal-dose group (100 kVp, 100 ml CM). Contrast-to-noise ratio (CNR) in the pulmonary trunk was calculated. Two blinded chest radiologists independently evaluated subjective image quality and diagnostic confidence. Data were compared between the normal-dose and low-dose groups in five BW subgroups. RESULTS Vessel attenuation did not differ between the normal-dose and low-dose groups within each BW subgroup (P = 1.0). The CNR was higher with the normal-dose compared with the low-dose protocol (P < 0.006) in all BW subgroups except for the 90-99 kg subgroup (P = 0.812). Subjective image quality and diagnostic confidence did not differ between CT protocols in all subgroups (P between 0.960 and 1.0). CONCLUSIONS Subjective image quality and diagnostic confidence with 80 kVp CTPA is not different from normal-dose protocol in any BW group up to 100 kg. KEY POINTS • 80 kVp CTPA is safe in patients weighing <100 kg • Reduced radiation and iodine dose still provide high vessel attenuation • Image quality and diagnostic confidence with low-dose CTPA is good • Diagnostic confidence does not deteriorate in obese patients weighing <100 kg.
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Optimization of contrast material delivery for dual-energy computed tomography pulmonary angiography in patients with suspected pulmonary embolism.
Nance, JW, Henzler, T, Meyer, M, Apfaltrer, P, Braunagel, M, Krissak, R, Schoepf, UJ, Schoenberg, SO, Fink, C
Investigative radiology. 2012;(1):78-84
Abstract
OBJECTIVES To prospectively compare subjective and objective measures of image quality using 4 different contrast material injection protocols in dual-energy computed tomography pulmonary angiography (CTPA) studies of patients with suspected pulmonary embolism. MATERIALS AND METHODS A total of 100 consecutive patients referred for CTPA for the exclusion of pulmonary embolism were randomized into 1 of 4 contrast material injection protocols manipulating iodine concentration and iodine delivery rate (IDR, expressed as grams of iodine per second): Iomeprol 400 at 3 mL/s (IDR = 1.2 gI/s), iomeprol 400 at 4 mL/s (IDR = 1.6 gI/s), iomeprol 300 at 5.4 mL/s (IDR = 1.6 gI/s), or iomeprol 300 at 4 mL/s (IDR = 1.2 gI/s). Total iodine delivery was held constant. Dual-energy CTPA of the lungs were acquired and used to calculate virtual 120 kV CTPA images as well as iodine perfusion maps. Attenuation values in the thoracic vasculature and image quality of virtual 120 kV CTPAs were compared between groups. Iodine perfusion maps were also compared by identifying differences in the extent of beam-hardening artifacts and subjective image quality. RESULTS Protocols with an IDR of 1.6 gI/s provided the best attenuation profiles. CTPA image quality was greatest in the high concentration, high IDR (1.6 gI/s) protocol (P < 0.05 for all group comparisons) with no differences between the other groups (all P ≥ 0.05). Extent of beam-hardening artifacts and perfusion map image quality was significantly better using the high concentration, high IDR protocol as compared with all groups (P < 0.05 for all comparisons) and significantly worse using the low concentration, low IDR protocol as compared with all groups (all P ≥ 0.05); no difference was found between the high concentration, low IDR protocol and the low concentration, high IDR protocol (P = 0.73 for comparison of beam-hardening artifacts; P = 0.50 for comparison of perfusion map image quality). CONCLUSION High iodine concentration and high IDR contrast material delivery protocols provide the best image quality of both CTPA and perfusion map images of the lung through high attenuation in the pulmonary arteries and minimization of beam-hardening artifacts.
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[Optimization of scan protocol in pulmonary angiography of second generation dual source computed tomography].
Chen, B, Zhang, WM, Hu, JB, Hu, HJ
Zhonghua yi xue za zhi. 2012;(31):2186-90
Abstract
OBJECTIVE To explore the scan protocol of second generation dual source computed tomography (CT) for CT pulmonary angiogram (CTPA) in patients with suspected pulmonary embolism and determine the proper volume of contrast medium. METHODS A total of 120 patients undergoing CTPA were recruited. All examinations were performed on a second generation dual source CT. The scan delay was determined with the test bolus technique. Four contrast volume protocols were designed, namely groups A, B, C and D respectively (n = 30 each). For CTPA scan of groups A, B, C and D, 35, 40, 45 and 50 ml contrast medium were injected at an injection rate of 4 ml/s, followed by a saline chaser of 55, 50, 45 and 40 ml respectively. Attenuation profiles of different vascular segments (subclavian vein, vena cava, left atrium, pulmonary trunk, S1 artery, S10 artery) were measured to evaluate the timing techniques. The image quality and artifact of iodine map were analyzed by two radiologists for comparisons. RESULTS The percentage of pulmonary arteries exceeding optimal attenuation (> 200 HU) showed that groups of B, C and D were higher than group A (93% - 100% vs 80% - 90%). The image quality of group A was lower than the others (P < 0.05) while the other groups showed no significant difference. The artifacts of iodine map of group A were much fewer than the others (P < 0.05) and group D was much more than the other groups (P < 0.05). Groups B and C had a score of 4.13 and 3.67 respectively without significant difference (P = 0.091). CONCLUSION With the aids of test bolus technique and proper injection protocol (40 ml contrast medium followed by 50 ml saline), the high quality image and low volume of iodine can be realized with second generation dual source CT for CTPA.
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The increase in pulmonary arterial pressure caused by hypoxia depends on iron status.
Smith, TG, Balanos, GM, Croft, QP, Talbot, NP, Dorrington, KL, Ratcliffe, PJ, Robbins, PA
The Journal of physiology. 2008;(24):5999-6005
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Abstract
Hypoxia is a major cause of pulmonary hypertension. Gene expression activated by the transcription factor hypoxia-inducible factor (HIF) is central to this process. The oxygen-sensing iron-dependent dioxygenase enzymes that regulate HIF are highly sensitive to varying iron availability. It is unknown whether iron similarly influences the pulmonary vasculature. This human physiology study aimed to determine whether varying iron availability affects pulmonary arterial pressure and the pulmonary vascular response to hypoxia, as predicted biochemically by the role of HIF. In a controlled crossover study, 16 healthy iron-replete volunteers undertook two separate protocols. The 'Iron Protocol' studied the effects of an intravenous infusion of iron on the pulmonary vascular response to 8 h of sustained hypoxia. The 'Desferrioxamine Protocol' examined the effects of an 8 h intravenous infusion of the iron chelator desferrioxamine on the pulmonary circulation. Primary outcome measures were pulmonary artery systolic pressure (PASP) and the PASP response to acute hypoxia (DeltaPASP), assessed by Doppler echocardiography. In the Iron Protocol, infusion of iron abolished or greatly reduced both the elevation in baseline PASP (P < 0.001) and the enhanced sensitivity of the pulmonary vasculature to acute hypoxia (P = 0.002) that are induced by exposure to sustained hypoxia. In the Desferrioxamine Protocol, desferrioxamine significantly elevated both PASP (P < 0.001) and DeltaPASP (P = 0.01). We conclude that iron availability modifies pulmonary arterial pressure and pulmonary vascular responses to hypoxia. Further research should investigate the potential for therapeutic manipulation of iron status in the management of hypoxic pulmonary hypertensive disease.