Pulmonary vasodilation in acute pulmonary embolism - a systematic review

Acute pulmonary embolism is the third most common cause of cardiovascular death. Pulmonary embolism increases right ventricular afterload, which causes right ventricular failure, circulatory collapse and death. Most treatments focus on removal of the mechanical obstruction caused by the embolism, but pulmonary vasoconstriction is a significant contributor to the increased right ventricular afterload and is often left untreated. Pulmonary thromboembolism causes mechanical obstruction of the pulmonary vasculature coupled with a complex interaction between humoral factors from the activated platelets, endothelial effects, reflexes and hypoxia to cause pulmonary vasoconstriction that worsens right ventricular afterload. Vasoconstrictors include serotonin, thromboxane, prostaglandins and endothelins, counterbalanced by vasodilators such as nitric oxide and prostacyclins. Exogenous administration of pulmonary vasodilators in acute pulmonary embolism seems attractive but all come with a risk of systemic vasodilation or worsening of pulmonary ventilation-perfusion mismatch. In animal models of acute pulmonary embolism, modulators of the nitric oxide-cyclic guanosine monophosphate-protein kinase G pathway, endothelin pathway and prostaglandin pathway have been investigated. But only a small number of clinical case reports and prospective clinical trials exist. The aim of this review is to give an overview of the causes of pulmonary embolism-induced pulmonary vasoconstriction and of experimental and human investigations of pulmonary vasodilation in acute pulmonary embolism

Putative Biomarkers for Acute Pulmonary Embolism in Exhaled Breath Condensate

Current diagnostic markers for pulmonary embolism (PE) are unspecific. We investigated the proteome of the exhaled breath condensate (EBC) in a porcine model of acute PE in order to identify putative diagnostic markers for PE. EBC was collected at baseline and after the induction of autologous intermediate-risk PE in 14 pigs, plus four negative control pigs. The protein profiles of the EBC were analyzed using label-free quantitative nano liquid chromatography–tandem mass spectrometry. A total of 897 proteins were identified in the EBCs from the pigs. Alterations were found in the levels of 145 different proteins after PE compared with the baseline and negative controls: albumin was among the most upregulated proteins, with 14-fold higher levels 2.5 h after PE (p-value: 0.02). The levels of 49 other proteins were between 1.3- and 17.1-fold higher after PE. The levels of 95 proteins were lower after PE. Neutrophil gelatinase-associated lipocalin (fold change 0.3, p-value < 0.01) was among the most reduced proteins 2.5 h after PE. A prediction model based on penalized regression identified five proteins including albumin and neutrophil gelatinase-associated lipocalin. The model was capable of discriminating baseline samples from EBC samples collected 2.5 h after PE correctly in 22 out of 27 samples. In conclusion, the EBC from pigs with acute PE contained several putative diagnostic markers of PE

Mechanisms, predictors, and evolution of severe peri-device leaks with two different left atrial appendage occluders.

AIMS Incomplete left atrial appendage occlusion (LAAO) due to peri-device leak (PDL) is a limitation of the therapy. The Amulet IDE trial is the largest randomized head-to-head trial comparing the Amulet and Watchman 2.5 LAAO devices with fundamentally different designs. The predictors and mechanistic factors impacting differences in PDLs within the Amulet IDE trial are assessed in the current analysis. METHODS AND RESULTS An independent core lab analysed all images for the presence or absence of severe PDL (>5 mm). The incidence, mechanistic factors, predictors using propensity score-matched controls, and evolution of severe PDLs through 18 months were assessed. Of the 1878 patients randomized in the trial, the Amulet occluder had significantly fewer severe PDLs than the Watchman device at 45 days (1.1 vs. 3.2%, P < 0.001) and 12 months (0.1 vs. 1.1%, P < 0.001). Off-axis deployment or missed lobes were leading mechanistic PDL factors in each device group. Larger left atrial appendage (LAA) dimensions including orifice diameter, landing zone diameter, and depth predicted severe PDL with the Watchman device, with no significant anatomical limitations noted with the Amulet occluder. Procedural and device implant predictors were found with the Amulet occluder attributed to the learning curve with the device. A majority of Watchman device severe PDLs did not resolve over time through 18 months. CONCLUSION The dual-occlusive Amplatzer Amulet LAA occluder provided improved LAA closure compared with the Watchman 2.5 device. Predictors and temporal observations of severe PDLs were identified in the Amulet IDE trial. CLINICAL TRIAL REGISTRATION https://clinicaltrials.gov Unique identifier NCT02879448

Clinical outcomes of patients undergoing percutaneous left atrial appendage occlusion in general anaesthesia or conscious sedation: data from the prospective global Amplatzer Amulet Occluder Observational Study

Objective To evaluate the safety and efficacy of percutaneous left atrial appendage occlusion (LAAO) using conscious sedation (CS).Background Several percutaneous structural heart disease interventions are safely and efficiently performed using CS instead of general anaesthesia (GA). This concept has not been evaluated in a large multicenter cohort of patients undergoing LAAO.Methods Patients from the prospective, global Amplatzer Amulet Occluder Observational Study were divided into two groups (GA vs CS). Baseline information, periprocedural and postprocedural efficacy and complications, as well as outcomes through 7 days post implant were compared.Results Patients undergoing transesophageal-guided implants were categorised by GA (n=607, 64%) or CS (n=342, 36%) usage. Mean age was 75 years in both groups. LAAO technical success was achieved in 99% of both groups. The procedure duration (GA: 35 +/- 22 min vs CS: 27 +/- 19 min, pConclusions In a large global study, LAAO with the Amplatzer Amulet occluder is safe and feasible using CS. Procedure duration and total amount of contrast were less with CS than GA cases.</p

Length of stay following percutaneous left atrial appendage occlusion: Data from the prospective, multicenter Amplatzer Amulet Occluder Observational Study

Aims To evaluate factors influencing the length of stay in patients undergoing percutaneous left atrial appendage occlusion (LAAO). Methods and results Patient characteristics, procedural data and the occurrence of serious adverse events were analyzed from the Amplatzer Amulet Occluder Observational Study. Patients were divided into three groups: same day (S, 0day, n = 60, 5.6%) early (E, 1day, n = 526, 48.9%), regular (R, 2-3days, n = 338, 31.4%) and late (L, >= 4days, n = 152, 14.1%) discharge and followed up for 60 days. Procedure and device related SAE during the in-hospital stay (S: 0.0% vs. E: 1.0% vs. R: 2.1% vs. L: 23%, pConclusion Over half of the subjects receiving an Amplatzer Amulet occluder were discharged within 1 day of the implant procedure. Serious adverse events were a major trigger for a late discharge after LAAO. Increased HAS-BLED score was associated with a prolonged in-hospital stay.</p

Riociguat treatment in patients with chronic thromboembolic pulmonary hypertension: Final safety data from the EXPERT registry

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase