Decrease In Mean Pulmonary Artery Pressure Research Articles

Acute vasoreactivity testing for severe pulmonary hypertension associated with lung disease

Abstract Background Pulmonary hypertension results in clinical deterioration and increases mortality risk in patients with lung disease (LD), including chronic obstructive pulmonary disease, interstitial lung disease and combined pulmonary fibrosis and emphysema. Though acute vasoreactivity testing predicts long term-survival of patients with pulmonary arterial hypertension (PAH), its clinical impact for patients with pulmonary hypertension associated with LD (LD-PH) remains unknown. Purpose The purpose of this study is to clarify the clinical impact of acute vasoreactivity testing using inhaled nitric oxide for severe LD-PH. Methods We retrospectively reviewed 65 consecutive patients with LD-PH between January 2014 and December 2022; 48 patients (73 [68–78] years; males, 81%; median follow-up period 23 [7–35] months) with severe pulmonary hypertension who underwent acute vasoreactivity testing were included. We divided the patients based on a median pulmonary vascular resistance (PVR) response (−15%) in acute vasoreactivity testing into the high-responder (PVR response ≦−15%) and the low-responder (PVR response >−15%) groups. Results Acute vasoreactivity testing significantly decreased mean pulmonary arterial pressure (mPAP) (from 41 [34–48] to 36 [31–40] mmHg, P<0.01) and PVR (from 10.7 [8.3–13.8] to 8.9 [6.6–11.4] Wood units, P<0.01). The high-responder group had better long-term survival than the low-responder group (P = 0.03). Univariate Cox regression analysis showed that the prognostic factors for better survival included younger age, high-responder to acute vasoreactivity testing, and PAH-specific therapy (P <0.01, 0.04, 0.03, respectively). There were correlations between the PVR response at acute vasoreactivity testing and improvement in mPAP (R=0.40, P=0.03) or PVR (R = 0.47, P <0.01) with PAH-specific therapy. Conclusions PVR response at acute vasoreactivity testing was associated with better long-term survival and haemodynamic improvement with PAH-specific therapy. Acute vasoreactivity testing may be useful to predict the responders to PAH-specific therapy and long-term survival in patients with severe LD-PH.

Evaluating haemodynamic changes: vericiguat in patients with heart failure with reduced ejection fraction.

Vericiguat has been used to treat patients with heart failure with reduced ejection fraction (HFrEF) who demonstrated worsening heart failure despite treatment with other guideline-directed medical therapies. The haemodynamic effects of vericiguat remain unclear. This study enrolled 12 patients (median age, 63 [quartiles 53.5, 70] years; 16.7%(N=2) women) with symptomatic HFrEF (New York Heart Association functional class II-IV) who demonstrated worsening heart failure despite treatment with the four foundational guideline-recommended therapies between March and December 2022, with follow-ups completed in June 2023. A balloon-tipped pulmonary artery thermodilution catheter was placed in the right internal jugular vein to perform right heart catheterisation (RHC) on day 1. Haemodynamic data were acquired before and after vericiguat intake (2.5mg) on days 2 and 3. The data on days 2 and 3 were averaged. RHC was repeated on day 105 (37, 168). Oral intake of vericiguat 2.5mg decreased mean pulmonary artery pressure (19.3 [14.3, 26.8] mmHg) and pulmonary artery wedge pressure (PAWP) (11 [7.5, 15] mmHg) before the intake to mean pulmonary artery pressure (17.5 [12.5, 24] mmHg) and PAWP (9.3 [6.8, 14] mmHg) at 30min after (both P<0.05). Reduction in PAWP was also found from 14.5 [9.5, 19.5] mmHg on day 1 to 9.5 [6.5, 12.5] mmHg on day 105 (37, 168) (P<0.05), when vericiguat was titrated to 2.5mg 25% (N=3), 5mg 50% (N=6), and 10mg 25% (N=3). The consistent reduction in PAWP underscores the well-tolerated nature of vericiguat and its potential to enhance cardiac performance in patients with HFrEF.

Effect of Acute Vasodilator Testing Using Oxygen in Pulmonary Hypertension Due to Left Heart Disease.

Pulmonary vasodilators, including oxygen, have not shown consistent beneficial effects on pulmonary hypertension due to valvular heart disease (PH-VHD). Therefore, the study aimed to assess the effect of 100% fractional inspiration of oxygen (FiO2) on pulmonary and systemic hemodynamics in patients with combined pre- and post-capillary pulmonary hypertension (CpcPH) and isolated post-capillary pulmonary hypertension (IpcPH) due to PH-VHD. This prospective study was conducted among patients with PH-VHD undergoing mitral or aortic valve replacement or repair. The study was conducted after induction of anesthesia and pulmonary artery catheterization. Cardiac output was obtained using thermodilution and all direct, and derived hemodynamic variables were obtained at 30% and 100% FiO2. The patients were stratified a priori into responders {(≥10mmHg fall in mean pulmonary artery pressure (MPAP)} and non-responders. Fifty-seven patients completed the acute vasodilator test. The mean age and body mass index of the study population was 41.8 ± 14.1years and 21.4 ± 4.6kg/m2, respectively. There was a significant decrease in MPAP (40.77 ± 12.07mmHg vs 36.74 ± 13.3mmHg; P < .001) and pulmonary vascular resistance (PVR) {(median; Interquartile range (IQR); 388; 371 vs 323; 362dynes sec.cm-5; P < .001) at 100% FiO2. Transpulmonary gradient (TPG) and diastolic pulmonary gradient (DPG) also decreased significantly (P < .001 and P < .001). Cardiac output did not change significantly. The magnitude of decrease in MPAP, PVR, TPG, DPG, and pulmonary artery compliance (PAC) between CpcPH and IpcPH was comparable. Responders did not show a significantly greater fall in MPAP, PVR, TPG, DPG, and PAC after surgery. Hyperoxia may lead to reduction in MPAP and PVR in both hemodynamic phenotypes of PH-VHD. A larger sample size is required to support or refute the findings of this study.

Echinacoside inhibits PASMCs calcium overload to prevent hypoxic pulmonary artery remodeling by regulating TRPC1/4/6 and calmodulin.

Research indicates that hypoxic pulmonary hypertension (HPH) potentially stimulates the sympathetic nervous system, which may increase norepinephrine (NE) release and cause excessive Ca2+ influx into pulmonary artery smooth muscle cells (PASMCs), leading to calcium overload and abnormal PASMC proliferation, factors closely associated with pulmonary vascular remodeling (PVR). This study investigates the potential mechanisms underlying echinacoside (ECH) treatment in HPH. In the in vitro experiment, NE-induced PASMCs were used to simulate HPH-induced PASMCs' calcium overload and abnormal proliferation. Postincubation with ECH, [Ca2+]cyt changes were detected using Fluo-4 AM. Flow cytometry was employed to ascertain ECH's inhibitory effect on PASMCs proliferation. For in vivo experiments, rats were exposed to a hypoxic and low-pressure oxygen environment to establish the HPH model. Post-ECH treatment, hematoxylin and eosin (HE) staining was conducted to assess PVR, and western blot analysis was used to examine protein expression in the lung tissues of the different groups. ECH was observed to inhibit [Ca2+]cyt increase in NE-induced PASMCs in a concentration-dependent manner, effectively reducing abnormal cell proliferation. It also reduced the expression of Transient receptor potential channel (TRPC) 1 (TRPC1), TRPC4, TRPC6, and calmodulin in PASMCs. In vivo studies demonstrated that ECH lowered the expression of these proteins in lung tissues of HPH rats, significantly decreased mean pulmonary artery pressure, and mitigated PVR.

Large-bore aspiration thrombectomy versus catheter-directed thrombolysis for the treatment of pulmonary embolism: A retrospective case review from a community hospital

Objectives: This study aimed to assess acute outcomes following pulmonary embolism (PE) treatment with large-bore aspiration thrombectomy (LBAT) versus catheter-directed thrombolysis (CDT). Material and Methods: This single-center retrospective analysis included patients who received interventional therapy for acute PE from 2018 to 2022. The primary outcomes were changes in pre-procedural mean pulmonary artery pressure (PAP), heart rate (HR), oxygen saturation, and supplemental requirements following the procedure. Mean PAP was measured immediately post-procedure for LBAT patients and on postoperative day 1 (POD#1) for CDT patients. Results: A total of 48 patient cases were reviewed, 31 underwent LBAT and 17 underwent CDT. The majority of patients were female and most had intermediate-high-risk PE. No major bleeding events or device-related complications occurred. LBAT resulted in a significant decrease in average mean PAP immediately post-procedure (31.3 ± 9.0–21.4 ± 8.1 mmHg; P &lt; 0.001). On POD#1, CDT resulted in a significant decrease in mean PAP (31.7 ± 11.2–25.6 ± 7.9 mmHg; P = 0.005). The decrease in mean PAP was greater in the LBAT versus CDT group (P &lt; 0.05). Through POD#1, a similar reduction in average HR was observed between groups; however, a statistically significant reduction in HR was noted immediately post-procedure with LBAT and not with CDT. LBAT patients had a significant reduction in average supplemental oxygen requirements post-procedure. Conclusion: LBAT was associated with a greater reduction in mean PAP than CDT at an earlier post-procedural time point. LBAT may be advantageous over CDT due to rapid thrombus extraction; however, further studies with increased sample sizes are needed. Evidence-based medicine: Level of Evidence: Level 3, Local non-random sample.

Effectiveness and Safety of Large-Bore Aspiration Thrombectomy for Intermediate- or High-Risk Pulmonary Embolism

PurposeTo evaluate effectiveness and safety of large-bore mechanical thrombectomy of intermediate- or high-risk pulmonary embolism (PE) and factors associated with effectiveness. Materials and MethodsA retrospective review of 257 patients with intermediate- or high-risk PE who underwent mechanical thrombectomy using the Flowtriever system (Inari Medical, Irvine, California) between July 2019 and November 2021 was conducted. Data were analyzed using the linear regression and Kaplan-Meier methods with a Type 1 error set at 0.05. ResultsPatients’ mean age was 62 years, and 51% were male. PE risk was classified as high, intermediate-high, and intermediate-low in 37 (14%), 201 (78%), and 18 (7%) of the patients, respectively. Procedural technical success was 100%. The mean pulmonary artery pressure (MPAP) decreased from a mean of 32 mmHg (SD ± 9) before to 24 mmHg (SD ± 9) after thrombectomy (mean decrease, 8 mmHg [SD ± 6]; P < .0001). Immediate complications occurred in 2% of the patients. Postprocedural 30-day and all-time PE-attributable mortality in a mean of 1.3-year follow-up was 2% and 6%, respectively. In multivariate analysis, the presence of lower extremity DVT at presentation (β ± SE, −7.60 ± 3.22; P = .019) and a higher prethrombectomy MPAP (β ± SE, −0.19 ± 0.04; P < .001) were associated with lower degrees of decrease in MPAP in the intermediate-high–risk PE group. Among 14 patients with postthrombectomy PE-attributable mortality, 13 had postthrombectomy MPAPs of >20 mmHg. ConclusionsLarge-bore aspiration thrombectomy is a safe and effective treatment for reducing PAP in patients with intermediate- or high-risk PE. Postthrombectomy MPAPs of >20 mmHg might indicate postthrombectomy PE-attributable mortality in high-risk patients.

P98: Hemodynamic Effects of Minimally Invasive Mechanical Circulatory Support – Impella 5.5 versus Intra-Aortic Balloon Pump

Background: While the hemodynamic benefits of durable LVADs and intra-aortic balloon pumps (IABPs) in patients with acute-on-chronic heart failure are well described, the hemodynamic effects of the minimally-invasive Impella 5.5 in this patient population are not. Methods: Patient and hemodynamic data on all Impella 5.5 and IABP recipients between August 2020-November 2022 were extracted from a single-institutional database. Only patients with a history of decompensated chronic congestive heart failure were included. Patients requiring Impella support after myocardial infarction or immediately after cardiac surgery were excluded. The primary outcome was survival at 30 days after implantation. Secondary outcomes included changes in pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) between device implantation and removal. Results: We identified 25 Impella 5.5 patients (12.0% female), 68 IABP patients (19.1% female), and 21 patients who had IABP exchanged for Impella 5.5 (14.2% female). There were no significant differences in baseline characteristics or hemodynamics between Impella 5.5 and isolated IABP patients (Table). Median support duration was significantly longer in the Impella 5.5 cohort (11 days vs. 8 days, p = 0.04). There was no significant difference in survival at 30 days between groups (Figure). PVR and PCWP significantly decreased in both cohorts, while CI significantly increased (Table). The percent increase in CI was significantly greater in Impella 5.5 patients than in IABP patients (67.8% vs 33.6%, p=0.01). However, only the IABP cohort demonstrated significantly decreased mean pulmonary artery pressure (PAP) (-7.0 mmHg, p<0.01) and central venous pressure (CVP) (-3.5 mmHg, p=0.03). Exchanging IABP to Impella 5.5 significantly improved PVR (-50.92 dynes sec cm-5, p=0.03), but not other hemodynamic parameters. Conclusion: Both IABP and Impella 5.5 improve hemodynamics by decreasing pulmonary congestion and increasing cardiac output. While only the IABP significantly decreased mean PAP and CVP, the Impella 5.5 provided greater improvements in CI, and exchanging IABP for Impella 5.5 provided further reductions in PVR.Figure 1. 30-day survival after Impella 5.5 or IABP. - IABP (n=68) Impella 5.5 (n=25) P-value Age 59.10 (47.12-64.97) 44.58 (40.3-63.2) 0.1824 Female 19.1% (13/68) 12.0% (3/25) 0.5442 ICM 30.9% (21/68) 40.3% (10/25) 0.4585 Pre-op PVR 240.0 (176.0-344.0) 231.0 (191.8-344.0) 0.4294 Pre-op PCWP 30.0 (26.0-34.0) 27.0 (20.5-34.0) 0.1186 Pre-op mean PAP 41.5 (37.8-48.0) 40.0 (32.5-49.3) 0.1964 Pre-op CVP 14.0 (10.0-12.5) 14.0 (10.0-22.0) 0.3746 Pre-op CO 3.6 (3.0-4.4) 3.6 (3.0-4.6) 0.3184 Pre-op CI 1.7 (1.5-2.1) 1.9 (1.5-2.2) 0.3184 IABP => Impella 5.5 Pre-exchange Pre-explant P-value PVR 184.4 (111.9-253.1) 148.2 (94.45-214.2) 0.0290 PCWP 23.0 (18.8-27.8) 22.0 (16.0-31.0) 0.3398 Mean PAP 34.5 (29.0-38.3) 35.0 (32.0-38.0) 0.2142 CVP 12.0 (7.50-20.5) 13.0 (9.8-18.8) 0.4431 CO 4.3 (3.3-5.4) 4.9 (4.0-6.1) 0.1832 CI 2.1 (1.6-2.8) 2.3 (2.1-2.6) 0.1526

CLOT IN TRANSIT: THE ROLE OF POINT-OF-CARE ULTRASOUND IN EARLY DIAGNOSIS AND IMPROVED OUTCOMES

CLOT IN TRANSIT: THE ROLE OF POINT-OF-CARE ULTRASOUND IN EARLY DIAGNOSIS AND IMPROVED OUTCOMES

Do alterations in pulmonary vascular tone result in changes in central blood volumes? An experimental study

BackgroundThe effects of selective pulmonary vascular tone alterations on cardiac preload have not been previously examined. Therefore, we evaluated whether changing pulmonary vascular tone either by hypoxia or the inhalation of aerosolized prostacyclin (PGI2) altered intrathoracic or pulmonary blood volume (ITBV, PBV, respectively), both as surrogate for left ventricular preload. Additionally, the mean systemic filling pressure analogue (Pmsa) and pressure for venous return (Pvr) were calculated as surrogate of right ventricular preload.MethodsIn a randomized controlled animal study in 6 spontaneously breathing dogs, pulmonary vascular tone was increased by controlled moderate hypoxia (FiO2 about 0.10) and decreased by aerosolized PGI2. Also, inhalation of PGI2 was instituted to induce pulmonary vasodilation during normoxia and hypoxia. PBV, ITBV and circulating blood volume (Vdcirc) were measured using transpulmonary thermo-dye dilution. Pmsa and Pvr were calculated post hoc. Either the Wilcoxon-signed rank test or Friedman ANOVA test was performed.ResultsDuring hypoxia, mean pulmonary artery pressure (PAP) increased from median [IQR] 12 [8–15] to 19 [17–25] mmHg (p < 0.05). ITBV, PBV and their ratio with Vdcirc remained unaltered, which was also true for Pmsa, Pvr and cardiac output. PGI2 co-inhalation during hypoxia normalized mean PAP to 13 (12–16) mmHg (p < 0.05), but left cardiac preload surrogates unaltered. PGI2 inhalation during normoxia further decreased mean PAP to 10 (9–13) mmHg (p < 0.05) without changing any of the other investigated hemodynamic variables.ConclusionsIn spontaneously breathing dogs, changes in pulmonary vascular tone altered PAP but had no effect on cardiac output, central blood volumes or their relation to circulating blood volume, nor on Pmsa and Pvr. These observations suggest that cardiac preload is preserved despite substantial alterations in right ventricular afterload.

Riociguat therapy for pulmonary hypertension: a systematic review and meta-analysis.

Riociguat therapy has been recommended for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), and it might have therapeutic significance for other types of pulmonary hypertension (PH). Our purpose was to evaluate the specific impact of riociguat on all types of PH. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the safety and efficacy of riociguat treatment for PH through databases of the Cochrane Library, PubMed, Embase, and Web of Science from inception to the present. Duplicate publications, studies with no full text, incomplete information or inability to extract data, animal experiments and reviews, and systematic reviews were excluded. The software RevMan 5.4 was used for data synthesis. There were 8 RCTs included in our study, involving 1,606 participants. For PAH and CTEPH patients, riociguat treatment extended 6-minute walk distance (6MWD) by 39.84 meters, decreased mean pulmonary arterial pressure (PAP) by 4.20 mmHg, lowered pulmonary vascular resistance (PVR) by 218.76 dynes/sec/cm-5, cut down right atrial pressure (RAP) by 0.9 mmHg, increased cardiac index (CI) by 0.49 L/min/m2, improved cardiac output (CO) by 0.89 L/min, reduced N-terminal pro-type B natriuretic peptide (NT-proBNP) by 436.21 pg/mL, and decreased adverse events and clinical worsening as compared with placebo. For other types of PH including PH due to left heart disease and PH due to lung disease, riociguat was reported as having improved CI by 0.42 L/min/m2 and CO was increased by 0.92 L/min compared with placebo. Other efficacy outcomes and safety outcomes did not attain statistical difference in other types of PH. For PAH and CTEPH, riociguat treatment is safe and effective, but for other types of PH, it can only improve some hemodynamic parameters.

MiR-125a-5p inhibits glycolysis by targeting hexokinase-II to improve pulmonary arterial hypertension.

Purpose: The aim of this study was to investigate the effect of microRNAs on the proliferation of pulmonary arterial smooth muscle cells (PASMCs) as a result of targeting hexokinase-II (HK-II) and its mechanism of action.Results: Differences in metabolic patterns were found between the normal group and monocrotaline-induced pulmonary arterial hypertension (MCT-PH) group. miR-125a-5p decreased glycolysis levels of monocrotaline (MCT)-induced PASMCs by targeting HK-II and inhibiting its proliferation. In vivo experiments found that miR-125a-5p agomir upregulated HK-II expression in the MCT-PH. Right ventricular hypertrophy was reversed and cardiac function improved as a result of decreased mean pulmonary artery pressure (mPAP).Conclusion: In vitro and in vivo experiments both confirmed that miR-125a-5p could inhibit cell glycolysis and PASMC proliferation to improve PAH by targeting HK-II.Methods: HK-II overexpression was constructed, and differentially expressed microRNAs were screened for using microarrays. Serum metabolites were detected using Nuclear Magnetic Resonance (NMR). Through screening for characteristic metabolites in rat body fluids and by analyzing biological functions, disordered metabolic pathways were identified. Activity of the miR-125a-5p target HK-II was measured using a luciferase reporter assay. Expression of downstream molecules was measured by RT–qPCR and/or western blot. Glucose consumption and lactic acid production were analyzed and used as a reflection of glycolysis.

Terlipressin Increases Systemic and Lowers Pulmonary Arterial Pressure in Experimental Acute Pulmonary Embolism.

We investigated whether the vasopressin-analog, terlipressin induces systemic vasoconstriction and pulmonary vasodilation in a porcine model of acute pulmonary embolism. Controlled, animal study. Tertiary medical center research laboratory. Female pigs (n = 12, Cross of Land Race, Duroc, and Yorkshire ~ 60 kg). Acute pulmonary embolism was induced by administration of three large autologous emboli. Animals then received four increasing doses of either terlipressin (n = 6) or vehicle (n = 6). Effects were evaluated in vivo at baseline, after pulmonary embolism and after each dose by invasive hemodynamic measures, transesophageal echocardiography, and blood analysis. Isolated pulmonary arteries were evaluated ex vivo in a myograph. Pulmonary embolism caused a four-fold increase in pulmonary vascular resistance (p < 0.0001) and a two-fold increase in mean pulmonary arterial pressure (p < 0.0001) compared with baseline. Terlipressin increased mean systemic blood pressure (28 ± 5 mm Hg; p < 0.0001) and systemic vascular resistance (1,320 ± 143 dynes; p < 0.0001) compared with vehicle. In the pulmonary circulation, terlipressin decreased mean pulmonary arterial pressure (-6.5 ± 1.8 mm Hg; p = 0.005) and tended to decrease pulmonary vascular resistance (-83 ± 33 dynes; p = 0.07). Terlipressin decreased cardiac output (-2.5 ± 0.5 L/min; p < 0.0001) and increased plasma lactate (2.7 ± 0.2 mmol/L; p < 0.0001), possibly indicating systemic hypoperfusion. A biomarker of cerebral ischemia, S100b, remained unchanged, suggesting preserved cerebral perfusion (0.17 ± 0.11 µg/L; p = 0.51). Ex vivo, terlipressin relaxed pulmonary and constricted mesenteric arteries. Terlipressin caused systemic vasoconstriction and pulmonary vasodilation in a porcine in vivo model of acute pulmonary embolism and vasorelaxation in isolated pulmonary arteries. Despite positive vascular effects, cardiac output declined and plasma lactate increased probably due to a predominantly systemic vasoconstrictor effect of terlipressin. These findings should warrant careful translation to the clinical setting and does not suggest routine use in acute pulmonary embolism.

Potential role of sympathetic activity on the pathogenesis of massive pulmonary embolism with circulatory shock in rabbits

BackgroundWe recently showed that intravenous sodium nitroprusside treatment (SNP) could relieve the pulmonary vasospasm of pulmonary embolism (PE) and non-pulmonary embolism (non-PE) regions in a rabbit massive pulmonary embolism (MPE) model associated with shock. The present study explored the potential role of cardiopulmonary sympathetic activity on the pathogenesis and the impact of vasodilators on cardiopulmonary sympathetic activity in this model.MethodsRabbits were randomly divided into sham operation group (S group, n = 8), model group (M, equal volume of saline intravenously, n = 11), SNP group (3.5 μg/kg/min intravenously, n = 10) and diltiazem group (DLZ, 6.0 μg/kg/min intravenously, n = 10).ResultsMPE resulted in reduced mean arterial pressure and increased mean pulmonary arterial pressure as well as reduced PaO2 in the M, SNP and DLZ groups. Tyrosine hydroxylase (TH), neuropeptide Y (NPY) and endothelin-1 (ET-1) expression levels were significantly increased, while nitric oxide (NO) levels were reduced in both PE and non-PE regions in the M group. Both SNP and DLZ decreased mean pulmonary arterial pressure, reversed shock status, downregulated the expression of TH, NPY and ET-1, and increased NO levels in PE and non-PE regions.ConclusionPresent results indicate that upregulation of the sympathetic medium transmitters TH and NPY in whole lung tissues serves one of the pathological features of MPE. The vasodilators SNP and DLZ could relieve pulmonary vasospasm in both embolization and non-embolization regions and reverse circulatory shock, thereby indirectly downregulating the sympathetic activation of the whole lung tissues and breaking a vicious cycle related to sympathetic activation in this model.

Meta-analysis of use of balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension

BackgroundCurrent guidelines give balloon pulmonary angioplasty (BPA) a Class IIb recommendation for use in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), as its safety and efficacy remain poorly defined. We conducted a systematic review and meta-analysis to evaluate BPA effectiveness. MethodsMedline, Cochrane Library and Scopus were searched for original studies from database inception dates until 24th May 2018. Prospective studies reporting outcomes before and after BPA in inoperable CTEPH patients were included. Studies with <20 patients were excluded. Data were pooled using a random effects model represented as weighted mean differences with 95% confidence intervals (CIs). ResultsSeventeen noncomparative studies comprising 670 CTEPH patients (mean age 62 years; 68% women) were included. Meta-analysis showed significantly decreased mean pulmonary artery pressure (−14.2 mm Hg [95% CI −18.9, −9.5]), pulmonary vascular resistance (−303.5 dyn·s/cm5 [95% CI −377.6, −229.4]) and mean right atrial pressure (−2.7 mm Hg [95% CI −4.1, −1.3]) after BPA. Six-minute walk distance (67.3 m [95% CI 53.8, 80.8]) and cardiac output (0.2 l/min [95% CI 0.0, 0.3]) were significantly increased following BPA. From 12 studies reporting mortality with median follow-up of 9 months after BPA (range, 1–51 months), pooled incidence of short (≤1 month) and long-term mortality (>1 month) was 1.9% and 5.7%, respectively. ConclusionThis systematic review and meta-analysis suggests mildly improved hemodynamics and overall low mortality rates following BPA in inoperable CTEPH patients. This non-comparative evidence can be used to facilitate decision making until the results of larger, controlled studies become available.

Clinical usefulness of right ventricular 3D area strain in the assessment of treatment effects of balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension: comparison with 2D feature-tracking MRI

To evaluate the usefulness of right ventricular (RV) area strain analysis via cardiac MRI (CMRI) as a tool for assessing the treatment effects of balloon pulmonary angioplasty (BPA) in inoperable chronic thromboembolic pulmonary hypertension (CTEPH), RV area strain was compared to two-dimensional (2D) strain with feature-tracking MRI (FTMRI) before and after BPA. We retrospectively analyzed 21 CTEPH patients who underwent BPA. End-systolic global area strain (GAS), longitudinal strain (LS), circumferential strain (CS), and radial strain (RS) were measured before and after BPA. Changes in GAS and RV ejection fraction (RVEF) values after BPA were defined as ΔGAS and ΔRVEF. Receiver operating characteristic (ROC) analyses were performed to determine the optimal cutoff of the strain at after BPA for detection of improved patients with decreased mean pulmonary artery pressure (mPAP) less than 30mmHg and increased RVEF more than 50%. ROC analysis revealed the optimal cutoffs of strains (GAS, LS, CS, and RS) for identifying improved patients with mPAP < 30mmHg (cutoff (%) = - 41.2, - 13.8, - 16.7, and 14.4: area under the curve, 0.75, 0.56, 0.65, and 0.75) and patients with RVEF > 50% (cutoff (%) = - 37.2, - 29.5, - 2.9, and 14.4: area under the curve, 0.81, 0.60, 0.56, and 0.56). Area strain analysis via CMRI may be a more useful tool for assessing the treatment effects of BPA in patients with CTEPH than 2D strains with FTMRI. • Area strain values can detect improvement of right ventricular (RV) pressure and function after balloon pulmonary angioplasty (BPA) equally or more accurately than two-dimensional strains. • Area strain analysis is a useful analytical method that reflects improvements in complex RV myocardial deformation by BPA. • Area strain analysis is a robust method with reproducibility equivalent to that of 2D strain analysis.

Efficacy and safety of catheter-directed interventional therapy in patients with acute pulmonary embolism

Objective: To evaluate the efficacy and safety of catheter-directed interventional therapy in patients with acute pulmonary embolism(PE). Methods: PE was diagnosed by CT pulmonary angiography(CTPA). After risk stratification, a total of 79 PE patients (age (58.9±14.9) years old)were treated with catheter-directed interventional therapy via pulmonary vessels. The changes of pulmonary hemodynamics were compared before and after treatment. The risk of complications and side effects were observed. Results: The pulmonary artery pressure was changed followed by interventional therapy. The interventional therapy significantly decreased mean pulmonary arterial pressure (mPAP) from (35.3±11.2)mmHg (1 mmHg=0.133 kPa) to (30.0±10.6)mmHg (t=8.803,P<0.05) and the echocardiographic derived right ventricular dimension to left ventricular dimension (RV/LV) ratio from 0.93±0.16 to 0.83±0.15 (t=6.868,P<0.05). The arterial partial pressure of oxygen was increased from (69.0±8.6)mmHg to (75.1±9.9)mmHg (t=8.561,P<0.05) . The oxygen saturation was also increased from (93.9±2.9)% to (95.1±1.9)% at 24 h after the treatment (t=2.621,P<0.05) . Patients were further grouped as high-risk group (n=28) and intermediate risk group (n=51). mPAP and RV/LV ratio were significantly reduced in the two subgroups (all P<0.05) and the range of reduction was more significant in the high-risk group. Five patients experienced minor bleeding complication, 3 patients suffered worsened dispone post procedure and were treated with mechanical ventilation, 1 patient died, and 1 patient developed recurrent PE. Conclusion: The catheter-directed interventional therapy improves pulmonary hemodynamics and reduces load of right ventricle both in high-risk or intermediate risk PE patients, this therapy strategy is safe and effective for patients with PE.

3-Bromopyruvate Attenuates Experimental Pulmonary Hypertension via Inhibition of Glycolysis.

The shift of metabolism from mitochondrial oxidative phosphorylation to glycolysis and mitochondria binding partner of hexokinase are features common to cancer. These have been seen in pulmonary hypertension (PH) as well. An inhibitor of hexokinase 2 (HK 2), the small molecule 3-bromopyruvate (3-BrPA) is an incredibly powerful and swift-acting anticancer agent. However, whether it could be of potential benefit to PH has still been unknown. Sprague-Dawley rats with monocrotaline (MCT)-induced PH were administered 2 oral doses of 3-BrPA (15 and 30 mg/kg/day, respectively) for 14 days. Hemodynamic parameters were obtained by right heart catheterization. Histopathology, immunohistochemistry, transmission electron microscopy, flow cytometry, and assessments of relative protein expressions were conducted. Compared with MCT treatment, 3-BrPA decreased mean pulmonary arterial pressure and pulmonary vascular resistance, and increased cardiac output. 3-BrPA significantly suppressed proliferation in addition to enhancing apoptosis of pulmonary artery smooth muscle cells, attenuating small pulmonary artery remodeling and right ventricular hypertrophy. Treatment with 3-BrPA markedly reduced the mitochondrial membrane potential and restored mitochondrial structure. Furthermore, 3-BrPA significantly inhibited HK 2 expression but not HK 1. The expression of both pyruvate dehydrogenase kinase and lactate dehydrogenase was decreased whereas that of pyruvate dehydrogenase and cytosolic cytochrome c was upregulated with 3-BrPA administration. This study demonstrates the reversal of PH by 3-BrPA is related to alteration in glycolysis and improved mitochondria function, indicating the "metabolic targeting" as a rational therapeutic strategy for PH.

Increasing mixed venous oxygen saturation is a predictor of improved renal function after balloon pulmonary angioplasty in patients with chronic thromboembolic pulmonary hypertension

Balloon pulmonary angioplasty (BPA) has emerged as an effective treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Renal function has been identified as a prognostic marker in patients with pulmonary hypertension in previous studies. We, therefore, aimed to investigate the clinical parameters associated with improvements in renal function in patients with CTEPH. A total of 45 consecutive patients with inoperable CTEPH undergoing BPA (mean age 62.2 ± 15.1years) were included in the study. We evaluated the patients' clinical characteristics at baseline and at 1-year post-BPA, and investigated the association between renal function and hemodynamic parameters, including right heart function. Hemodynamics and renal function showed sustained improvements at 1year after BPA in 64.4% of patients. Improved estimated glomerular filtration rate (eGFR) was significantly correlated with increased cardiac index (r = 0.433, p = 0.003) and mixed venous oxygen saturation (SvO2; r = 0.459, p = 0.002), and with decreased mean pulmonary arterial pressure (r = - 0.420, p = 0.004) and pulmonary vascular resistance (r = -- 0.465, p = 0.001). Multivariate analysis revealed that an increase in SvO2 immediately after the final BPA was associated with improved eGFR after the 1st year (odds ratio 1.041; 95% confidence interval 1.004-1.078; P = 0.027). The cut-off value for predicting improved eGFR was an increase in SvO2 after the final BPA of >125.4% over the baseline value (specificity 100%, sensitivity 24.1%). In conclusion, BPA improved symptoms, right heart function, hemodynamics, and renal function up to the chronic phase. Increasing SvO2 by >125.4% above baseline in the acute phase is important for improving renal function at 1year after BPA in CTEPH patients.

Electrical Vagal Nerve Stimulation Ameliorates Pulmonary Vascular Remodeling and Improves Survival in Rats With Severe Pulmonary Arterial Hypertension

This study aimed to elucidate the therapeutic effects of electrical vagal nerve stimulation (VNS) onsevere pulmonary arterial hypertension in a rat model. In a pathophysiological study, VNS significantly restored autonomic balance, decreased mean pulmonary arterial pressure, attenuated pulmonary vascular remodeling, and preserved right ventricular function. In a survival study, VNSsignificantly improved the survival rate in both the prevention (VNS from 0 to 5 weeks afteraSU5416 injection) and treatment (VNS from 5to 10 weeks) protocols. Thus, VNS may serveasanovel therapeutic strategy for pulmonary arterial hypertension.

THE HEMODYNAMICS AND RENAL FUNCTION BEFORE AND AFTER PULMONARY THROMBOENDARTERECTOMY

Objective: to study the pulmonary hemodynamics and kidney function in patients with chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary thromboendarterectomy (PTE). To analyze the main results of PTE.Material and methods: among 51 patients with CTEPH undergoing PTE, the group with chronic kidney disease (CKD) was identified. The main parameters of hemodynamics, such as cardiac output (CO), cardiac index (d), pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR), were determined. The cases of acute kidney injury (AKI) after PTE were identified. The correlation between hemodynamics and renal function was analyzed.Results: there was decrease of mean PAP, PVR and increase of CO and CI after PTE. In cases of AKI 1-2, the complete recovery of renal function were observed. Glomerular filtration rate (GFR) increased before discharge in patients with CKD and in other patients.Conclusion: the positive dynamics of renal function in patients with CTEPH after PTE is more probably associated with an increase in the С and renal perfusion.