Decrease In mPAP Research Articles

Clinical usefulness of endothelial progenitor cells in predicting the efficacy of riociguat in chronic thromboembolic pulmonary hypertension.

Endothelial dysfunction is important in the pathology of pulmonary hypertension, and circulating endothelial progenitor cells (EPCs) have been studied to evaluate endothelial dysfunction. In patients with chronic thromboembolic pulmonary hypertension (CTEPH), riociguat reportedly increases the number of circulating EPCs. However, the relationship between EPC numbers at baseline and changes in clinical parameters after riociguat administration has not been fully elucidated. Here, we evaluated 27 treatment-naïve patients with CTEPH and analyzed the relationships between EPC number at diagnosis and clinical variables (age, hemodynamics, atrial blood gas parameters, brain natriuretic peptide, and exercise tolerance) before and after riociguat initiation. EPCs were defined as CD45dim CD34+ CD133+ cells and measured by flow cytometry. A low number of circulating EPCs at diagnosis was significantly correlated with increased reductions in mean pulmonary arterial pressure (mPAP) (correlation coefficient = 0.535, P = 0.004) and right atrial pressure (correlation coefficient = 0.618, P = 0.001) upon riociguat treatment. We then divided the study population into two groups according to the mPAP change: a weak-response group (a decrease in mPAP of 4 mmHg or less) and a strong-response group (a decrease in mPAP of more than 4 mmHg). The number of EPCs at diagnosis was significantly lower in the strong-response group than in the weak-response group (P = 0.022), but there were no significant differences in other clinical variables or in medication profiles. In conclusion, circulating EPC numbers could be a potential predictor of the therapeutic effect of riociguat in CTEPH patients.

Results of long-term riociguat therapy, including a switching strategy from sildenafil, in patients with pulmonary hypertension of various genesis

Aim: to study the influence of riociguat on the functional and hemodynamic status, remodeling of the right heart, as well as the safety of therapy in both previously untreated patients with idiopathic pulmonary arterial hypertension (IPAH) and inoperable chronic thromboembolic PH (CTEPH), and those not achieved treatment goals with sildenafil therapy and switching to riociguat.Materials and methods. A total of 161 pts with precapillary PH were included in the study; 137 pts completed the three-year observation period. Of 55 IPAH pts riociguat was started after diagnosis verification in 39 pts (subgroup 1); 16 pts previously taking sildenafil who did not achieve treatment goals comprised subgroup 2 of switching to riociguat. Of 82 inoperable CTEPH pts riociguat was started in 45 naїve pts; a switching strategy riociguat was implemented in 37 pts after 24-hour withdrawal of sildenafil. The dose titration of riociguat was started from 1 mg TID according to the standard algorithm up to 7.5 mg/day. By month 36 92.4% and 94.8% of pts with IPAH and CTEPH, respectively, received 7.5 mg/day. At baseline, at month 12, 24 and 36 all pts underwent a 6-minute walking test (6MWT) with the assessment of the dyspnea index according to the Borg scale and SpO2, echocardiography (Echo), right heart catheterization (RHC), and the safety profile was assessed.Results. At baseline, the proportion of pts with FC III-IV in CTEPH group compared to IPAH group, was significantly higher (70.7% vs 41.8%)); the distance in T6MX (d6MWT) was 291 [232;385] m vs 379 [300;448] m (p<0.001). CTEPH pts had lower values of sPAP, PVR, SaO2 and SvO2 assessed by RHC. In the switching subgroups 2 of pts with IPAH and CTEPH, achieved levels of sPAP (p=0.01), sRAP (p=0.001) and PVR (p=0.01) (RHC) were significantly lower than in subgroups 1. The baseline levels of CI and SV were significantly higher in subgroups 2 (p<0.05). During riociguat treatment in both subgroups of IPAH, a significant increase in d6MWT was achieved by 6 months with FC I-II (WHO) in 75% and 70% of patients. In the subgroup 1 to 36 months the greatest increase by 97m was achieved; in the switching subgroup the increase in d6MWT was noticed by month 6, which was maintained by month 36. In CTEPH patients, there was a significant improvement in FC (p=0.001) with ∆dT6MX 48m (p=0.001). In subgroup 1 with CTEPH, the d6MWT increase was 68.2m (p = 0.001), reaching 82.6m by month 36. In subgroup 2 the significant change of d6MWT were noted by the 1st year of FU, reaching 136.6m by month 36. In IPAH and CTEPH pts by month 36 of riociguat therapy, a significant decrease of mPAP, SPAP were found by echo, which was confirmed by RHC; there was a decrease in the basal size of the right ventricle (RV) (p=0.04) and an increase in RV FAC (p=0.04 and p=0.03, respectively). In subgroups 1, ∆SvO2 in ts with IPAH and CTEPH were significantly higher compared to subgroups 2. During FU period the proportion of low-risk pts increased to 26.7% in IPAH group and 44.8% in CTEPH group at month 36. In subgroups 2 riociguat therapy resulted in maintenance of treatment regimens throughout the year. Only 6.2% of pts by month 24 and 36 required the prescription of a 3d specific drug. No serious adverse events (AEs) were observed during treatment. The most common AEs were nasopharyngitis, nasal congestion, and dyspnea.Conclusions: Riociguat therapy for 36 months demonstrated a persistent positive effect on the functional and hemodynamic status, remodeling of the right heart both in previously untreated patients with IPH and inoperable CTEPH, and in patients from the switching groups who did not achieve treatment goals with sildenafil therapy.

A Novel Dual Energy Computed Tomography Score Correlates With Postoperative Outcomes in Chronic Thromboembolic Pulmonary Hypertension.

To compare dual-energy computed tomography (DECT) based qualitative and quantitative parameters in chronic thromboembolic pulmonary hypertension with various postoperative primary and secondary endpoints. This was a retrospective analysis of 64 patients with chronic thromboembolic pulmonary hypertension who underwent DECT. First, a clot score was calculated by assigning the following score: pulmonary trunk-5, each main pulmonary artery-4, each lobar-3, each segmental-2, and subsegmental-1 per lobe; the sum total was then calculated. The perfusion defect (PD) score was calculated by assigning 1 point to each segmental PD. The combined score was calculated by adding clot and PD scores. For quantitative evaluation, we calculated perfused blood volume (PBV) (%) of each lung and the sum of both lungs. Primary endpoints included testing association between combined score and total PBV with change in mean pulmonary arterial pressure ([mPAP], change calculated as preop minus postop values). Secondary endpoints included explorative analysis of the correlation between combined score and PBV with change in preoperative and postoperative pulmonary vascular resistance, change in preoperative 6-minute walk distance (6MWD), and immediate postoperative complications such as reperfusion edema, ECMO placement, stroke, death and mechanical ventilation for more than 48 hours, all within 1 month of surgery. Higher combined scores were associated with larger decreases in mPAP ( =0.27, P =0.036). On average, the decrease in mPAP (pre mPAP-post mPAP) increased by 2.2mmHg (95% CI: -0.6, 5.0) with each 10 unit increase in combined score. The correlation between total PBV and change in mPAP was small and not statistically significant. During an exploratory analysis, higher combined scores were associated with larger increases in 6MWD at 6 months postprocedure ( =0.55, P =0.002). Calculation of DECT-based combined score offers potential in the evaluation of hemodynamic response to surgery. This response can also be objectively quantified.

Frequency of acute vasodilator response (AVR) in incident and prevalent patients with pulmonary arterial hypertension: Results from the pulmonary vascular disease phenomics study.

The prevalence of acute vasodilator response (AVR) to inhaled nitric oxide (iNO) during right heart catheterization (RHC) is 12% in idiopathic pulmonary arterial hypertension (IPAH). AVR, however, is reportedly lower in other disease-associated pulmonary arterial hypertension (PAH), such as connective tissue disease (CTD). The prevalence of AVR in patients on PAH therapy (prevalent cases) is unknown. We sought to determine AVR prevalence in Group 1 PH in the PVDOMICS cohort of incident and prevalent patients undergoing RHC. AVR was measured in response to 100% O2 and O2 plus iNO, with positivity defined as (1) decrease in mean pulmonary artery pressure (mPAP) by ≥10 mmHg to a value ≤40 mmHg, with no change or an increase in cardiac output (definition 1); or (2) decrease in mPAP by ≥12% and pulmonary vascular resistance by ≥30% (definition 2). AVR rates and cumulative survival were compared between incident and prevalent patients. In 338 mainly prevalent (86%) patients, positive AVR to O2-only was <2%, and 5.1% to 16.9%, based on definition 1 and 2 criteria, respectively; following O2 + iNO. IPAH AVR prevalence (4.1%-18.7%) was similar to prior reports. AVR positivity was 7.7% to 15.4% in mostly CTD-PAH prevalent cases, and 2.6% to 11.8% in other PAH groups. Survival was 89% in AVRresponders versus 77% in nonresponders from PAH diagnosis, and 91% versus 86% from PVDOMICS enrollment (log-rank test p = 0.04 and p = 0.05, respectively). In conclusion, AVR in IPAH patients is similar to prior studies. AVR in non-IPAH patients was higher than previously reported. The relationship between PAH therapy, AVR response, and survival warrants further investigation.

Impact of residual pulmonary hypertension on long-term outcomes after pulmonary endarterectomy in the modern era.

Residual pulmonary hypertension (PH) negatively impacts long-term results following pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH). We sought to reveal whether modern PH therapy with PH-targeted medicine and balloon pulmonary angioplasty (BPA) improved long-term results of residual PH after PEA. Long-term findings of 80 patients who survived PEA between 2011 and 2019 were retrospectively investigated. One month after PEA, 30 patients developed residual PH defined as mean pulmonary artery pressure (mPAP) ≥25 mmHg, of whom 23 were treated by PH-targeted medicine and 9 by BPA. Patients with residual PH acquired considerably better functional status and exercise capacity after PEA, however, exhibited significantly worse survival rates than those without. Eleven patients died during follow-up: 8 patients with residual PH and 3 controls. Among patients with residual PH, the deceased had a significantly lower %decrease in mPAP from 1 month to 1 year following PEA (7.4 [-32.6 to 8.0] % vs. 10.4 [3.7-27.8] %, p = 0.03) and higher mPAP at 1 year following PEA (39.5 [33.25-42.5] vs. 27 [26-34] mmHg, p < 0.01) despite PH-targeted medicine than the survived. No patients passed away from right heart failure, and there was no difference between the groups in CTEPH-related mortality. Modern PH therapy was used to address the majority of residual PH. Long-term survival after PEA was negatively impacted by residual PH, but it appeared that long-term mortality was also correlated with unrelieved residual PH despite PH-targeted medicine. Modern PH therapy may have enhanced functional status and excercise capacity, and averted fatal right heart failure.

Long-term prognostic value of cardiac catheterization and acute vasodilator testing with inhaled iloprost in pediatric idiopathic pulmonary arterial hypertension.

To assess the long-term prognostic value of cardiac catheterization and acute vasodilator testing (AVT) with inhaled iloprost in children with idiopathic pulmonary arterial hypertension (IPAH).Data on 81 consecutive children with IPAH referred to our center who underwent cardiac catheterization and AVT between June 2008 and August 2019 were collected. The correlation between the invasive hemodynamic data and transplant-free survival was analyzed. Twenty-four patients died and 1 underwent lung transplantation during a median follow-up of 3.8 years, with a 5-year transplant-free survival rate of 64.9%. Univariate analysis showed that predictors associated with improved survival included a lower pulmonary vascular resistance index (PVRI), PVRI/systemic vascular resistance index (SVRI), mean pulmonary arterial pressure (mPAP)/mean systemic arterial pressure, mean right atrial pressure, and a higher cardiac index (CI), mixed systemic venous oxygen saturations (SvO2), and acute vasodilator response (AVR) according to the Barst criteria (decrease in mPAP and PVRI/SVRI ratio of >20% without a decrease in CI). In multivariate Cox regression analysis, Barst AVR and SvO2 were independently related to transplant-free survival. Multiple hemodynamic variables from cardiac catheterization and AVT with inhaled iloprost have important prognostic value for long-term survival in children with IPAH, of which pulmonary vasoreactivity defined by the Barst criteria and SvO2 are independent prognostic factors.

Carbon Dioxide and Alveolar Dead Space as a Prognostic Marker for Patients Undergoing Pulmorary Endarterectomy

<h3>Purpose</h3> In patients with chronic thromboembolic pulmonary hypertension (CTEPH) partial pressure of carbon dioxide (PCO2) at rest and exercise is reduced in proportion to disease severity and reflect the abnormality in ventilatory- efficiency and drive by increase in physiologic alveolar dead space. Our aim was to determine the value of the delta in PCO2 and the alveolar dead space (AVDSf) as prognostic marker after pulmonary endarterectomy (PEA) in CTEPH patients. <h3>Methods</h3> Between 2013-2020, 51 CTEPH patients undergoing PEA with 2-year follow-up were retrospectively analysed including cardiopulmonary exercise testing and hemodynamic measurements before and 1-year after PEA. PCO2 and AVDSf were analysed before and after PEA. <h3>Results</h3> PCO2 values before PEA measured during induction are significantly lower compared to the values at the end of PEA (mean 4.47 SD 0.653 vs 5.66 SD 0.83,p=0.000) and at postoperative day 1 (POD1) (mean 4.47 SD 0.65 vs 4.82 SD 0.73,p=0.000). Delta PCO2 (between before and after surgery) (mean 1.183 SD 1.18) as well as the delta pCO2 between the end of surgery and POD 1 (mean 0.354 SD 1.14) correlates significantly with postoperative NYHA improvement and mPAP-decrease at 1-year postoperative (p=0.19; p=0.00; p=0.000; p=0,000, respectively). PEA resulted in increase of Vo2max (mean 17.68mL/kg/min SD 6.14 vs 13.47mL/kg/min SD 5.13, p=0.000), oxygen uptake at aerobic threshold (mean 12.92 mL/kg/min SD 5.14, vs 10.03mL/kg/min SD 4.12, p=0.001), decrease of mPAP at 1-year postoperative (mean 26.37mmHg SD 8.64 vs 40.22mmHg SD 8.67, p=0.000), pulmonary vascular resistance (mean 3.193WU SD 1.69 vs 6.13WU SD 2.69, p=0.000) and improvement of NYHA (p=0.000) in comparison to preoperative values. AVDSf before PEA at induction (mean 0.055 SD 0.166), to the end of surgery (mean 0.336 SD 0.12) and at POD1 (mean 0.152 SD 0.15) was observed and correlated significantly with postoperative NYHA- improvement and mPAP decrease at 1-year postoperative (p=0.000; p=0.000; p=0.000 and p=0.000; p=0,000, p=0.000 respectively). <h3>Conclusion</h3> In patients with CTEPH undergoing PEA, markers for alveolar dead space and ventilation/prefusion mismatch may predict longterm outcome after surgery. If confirmed in a prospective way, these markers can support indicating and early start of additional treament modalities such as ballon angioplasty or medication.

Hemodynamic Implications of Sildenafil in Candidates for Heart Transplantation with Group 2 Pulmonary Hypertension: A Single Latin-American Center Registry

<h3>Purpose</h3> Heart failure is the most common cause of Group 2 pulmonary hypertension (PH). When it becomes fixed, it increases morbidity and mortality in heart transplantation (HTx). Reversing this situation is difficult, but the use of selective pulmonary vasodilators such as sildenafil could be a simple pharmacological tool in this setting. <h3>Objectives</h3> To analyze the prevalence of PH and the effect of Sildenafil in HTx candidates and its impact on mortality. <h3>Methods</h3> Patients who had undergone HTx over a ten-year period were analyzed retrospectively. PH was defined as mean pulmonary artery pressure (PAP) ≥25mmHg and/or pulmonary vascular resistance (PVR) > 3UW. Among the P with PH those who received sildenafil (Group A) and those who did not (Group B) were compared. Quantitative variables were compared with t-test or Mann-Whitney, and nominals with Fisher's test. Survival was analyzed using the log-rank test. A p<0.05 was considered significant <h3>Results</h3> From 01/2008 to 12/2018, 294 P undergone HTx, 30 P (10%) with combined transplantation, pediatric, re-transplantation, and without data, were excluded. Of the 217 P analyzed, 153 P (70%) presented PH, of whom 77P (51%) received sildenafil. Baseline characteristics are described in Table 1a. The causes for which 76 P (49%) with PH did not receive treatment with sildenafil were: intolerance to vasodilators, treatment with vasopressors, pulmonary congestion, and a tendency to reserve selective pulmonary vasodilators for those patients under previous treatment with ACEIs, ARAII or ARNI. Table 1b describes the hemodynamic variables for both groups. Table 1a shows a decrease in MPAP, transpulmonary gradient, and PVR without changes in cardiac index in Group A. There was no difference in mortality between both groups (graphic 1) <h3>Conclusion</h3> The use of Sildenafil in P with Group 2 PH could be an effective strategy to improve the hemodynamic profile during the candidacy for HTx, without impact on survival.

Outcome of Surgery for Chronic Thromboembolic Pulmonary Disease without Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a serious condition that results from incomplete resolution of thromboemboli in pulmonary arteries. Symptomatic patients with chronic thromboembolic disease may have normal hemodynamic at rest. The aim of this study is to evaluate the outcome of pulmonary endarterectomy (PEA) in symptomatic patients with chronic thromboembolic pulmonary disease (CTEPD) in the absence of pulmonary hypertension as currently defined (mean pulmonary artery pressure [mPAP] < 20 mm Hg). Here, we report four symptomatic patients with chronic thromboembolic and normal hemodynamic at rest (mPAP ≤20 mm Hg or 20 < mPAP < 25 mm Hg and pulmonary vascular resistance [PVR] < 240 dyn·s/cm5) who underwent PEA between September 2015 and September 2019. The main outcome measures were functional New York Heart Association class, 6-minute walk distance (6MWD), hemodynamic measures in right heart catheterization (RHC), morbidity, and mortality. There were significant improvement in function class (2.6 ± 0.54 vs. 1 ± 0.2, p = 0.00), mPAP (preoperative: 23.3 ± 0.5 mm Hg vs. postoperative: 18.6 ± 1.5 mm Hg, p = 0.02), 6MWD (preoperative: 378.2 ± 68.7 m vs. postoperative: 432.9 ± 44.5 m, p = 0.01), and PVR (215.33 ± 91 vs. 101 ± 32 dyn·s/cm5, p = 0.1) 6 months after surgery based on data from RHC which was done during exercise. Also, RHC showed a significant decrease in mPAP (preoperative: 37 ± 7.7 mm Hg vs. postoperative 28 ± 3.2 mm Hg, p = 0.06). PEA could improve function class and hemodynamic in patients with CTEPD. Considering hemodynamic improvement in this group of patients after PEA, definition of CTEPH may need to be revised.

Treatment effect prediction using CT after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

To evaluate whether the change in computed tomography pulmonary angiography (CTPA) metrics after balloon pulmonary angioplasty (BPA) can predict treatment effect in chronic thromboembolic pulmonary hypertension (CTEPH) patients. This study included 82 CTEPH patients who underwent both CTPA and right heart catheterization (RHC) before and at the scheduled time of 6 months after BPA. The diameters of the main pulmonary artery (dPA), ascending aorta (dAA), right atrium (dRA), right ventricular free wall thickness (dRVW), and right and left ventricles (dRV, dLV) were measured on CTPA. The correlation of the New York Heart Association functional class (NYHA FC), 6-minute walking distance (6MWD), brain natriuretic peptide (BNP) level, and calculated CT metrics with a decrease in mean pulmonary artery pressure (ΔmPAP) using RHC (used as the reference for BPA effect) was investigated. Using multiple regression analysis, independent variables were also identified. In univariate analysis, clinical indicators (NYHA FC, 6MWD, and BNP level) improved significantly after BPA and were significantly correlated with ΔmPAP (p < 0.01). In the univariate analysis of CTPA parameters, dPA, dRA, dPA/dAA ratio, dRVW, and dRV/dLV ratio decreased significantly and were significantly correlated with ΔmPAP (p < 0.01). Multivariate analysis demonstrated that decreased dPA (p = 0.001) and decreased dRA (p = 0.039) on CTPA were independent predictive factors of ΔmPAP. Decreased dPA and dRA on CTPA could predict a decrease in mPAP after BPA, thus potentially eliminating unnecessary invasive catheterization. • The reduction in mean pulmonary artery pressure after balloon pulmonary angioplasty in CTEPH patients was significantly correlated with the clinical indices improvement and CTPA parameter decrease. • The decreased diameter of the main pulmonary artery and the decreased diameter of the right atrium on CTPA were independent predictors of mean pulmonary artery pressure reduction.

Maxingxiongting mixture attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the rho-kinase signaling pathway.

To explore the mechanism of Maxingxiongting mixture (MXXTM) on pulmonary hypertension in a rat model established by intraperitoneal injection of monocrotaline solution, smoking and forced swimming. A total of 30 male Sprague-Dawley rats were randomly divided into five groups: control group, model group, high-dose of MXXTM group (HM), low-dose of MXXTM group (LM), and fasudil group. The mean pulmonary artery pressure (mPAP) was measured by using a miniature catheter. Lung tissue and right ventricular tissue sections were stained with hematoxylin-eosin. The right ventricle (RV) and left ventricle + septum (LV + S) were weighted. RV/(LV+S) was calculated to reflect the degree of right ventricular hypertrophy. Rho/Rho-kinase signaling pathway key proteins (RhoA, ROCK Ⅰ and ROCK Ⅱ) in rat right ventricular tissue were measured by Western blot analysis. The levels of serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and the levels of plasma renin activity (PRA), angiotensin Ⅱ (ANG-Ⅱ), aldosterone (ALD) in rat anticoagulated plasma were all measured by enzyme-linked immunosorbent assay. Compared with the control group, the mPAP and RV/(LV+S) in the model group were significantly increased. Administration of fasudil resulted in a significant decrease of mPAP and RV/ (LV+S). In the HM group and LM group, mPAP and RV/ (LV+S) were significantly lower than the model group. Compared with the control group, the contents of HIF-1α, VEGF, PRA, ANG-Ⅱ and ALD in the model group were significantly increased. The administration of fasudil and high-dose MXXTM significantly reduced the contents of HIF-1α, VEGF, PRA, ANG-II and ALD. Compared with the control group, the expression of RhoA, ROCK Ⅰ and ROCK Ⅱ in the right ventricle of the model group were significantly increased. The administration of fasudil and high-dose MXXTM significantly reduced the expression of RhoA and Rock Ⅱ proteins. Our results indicated that high-dose of MXXTM had similar effects on reducing pulmonary artery pressure and improving right ventricular remodeling to fasudil. However, MXXTM was unable to restore parameters above to control levels. MXXTM attenuates hypoxia pulmonary arterial hypertension to improve right ventricular hypertrophy by inhibiting the Rho-kinase signaling pathway.

Abstract 14298: Right Ventricular Strain Before and After Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension

Background: Right ventricular (RV) function is impaired in chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) may be an alternative treatment for patients (pts) who are not candidates for pulmonary thromboendarterectomy (PTE). We assessed the RV global and segmental strain patterns in pts who underwent BPA. Methods: Between 12/2016 and 5/2019, 22 pts had completed BPA treatment and had transthoracic echocardiograms (echos) before and after treatment. Of those 22 pts, 14 had echos with adequate imaging of the RV. Epsilon EchoInsight® was used to measure global and segmental RV strain. Tricuspid annular plane excursion (TAPSE) was also measured. Paired t-tests were used to determine mean differences for pre &amp; post BPA, and Pearson correlation coefficient was used to determine association with hemodynamics. Results: RV global longitudinal strain (GLS) significantly improved after BPA (-11.1±3.4 to -16.2±2.9 % p&lt;0.05). The apical and mid segmental strain also significantly improved after BPA (-5.0±9.1 to -12.5±7.5%, p=0.03; -13.3±6.2 to -17.5±5.4%, p&lt;0.01 respectively). Basal strain did not significantly change (-15.2±6.3 to -18.5±9.2%, p=0.22). Furthermore, TAPSE did not change significantly (1.87±0.5 to 1.95±0.5 cm, p=0.55). Hemodynamically, mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance (PVR) significantly decreased (40.3±10.5 to 34.0±10.3 mmHg, p=0.001 and 5.9±3.1 to 3.9±1.8 WU, p=0.01) while cardiac output remained unchanged (5.6±2.0 to 5.7±1.1 L/min, p=0.86). There was no correlation between improvement in RV GLS and decrease in mPAP and PVR. Conclusion: RV function as measured by RV GLS significantly improved after BPA, though only the mid and apical segments improved. TAPSE and RV basal strain did not change after BPA. Previous studies have shown that GLS did not improve significantly after PTE. Furthermore, TAPSE significantly decreases after PTE. The reasons for the difference in RV function after PTE vs BPA are not entirely clear, but may be due to operability and location of disease, as well as immediate post-operative RV stunning after PTE.

Outcomes of Liver Transplantation in Treated Portopulmonary Hypertension Patients With a Mean Pulmonary Arterial Pressure ≥35 mm Hg.

Background.Portopulmonary hypertension (POPH), pulmonary arterial hypertension (PAH) that develops in the setting of portal hypertension, affects 5%–6% of patients with liver disease and is associated with significant morbidity and mortality. A mean pulmonary arterial pressure (mPAP) threshold of 35 mm Hg is used to stratify perioperative risk and liver transplant eligibility in treated POPH patients but does not take into account the specific factors that contribute to the pressure elevation.Methods.In this case series, we describe the characteristics and posttransplant outcomes of patients with treated POPH and an mPAP ≥35 mm Hg and pulmonary vascular resistance (PVR) <250 dynes-s-cm−5 at or just before liver transplantation (LT). We also describe the effect of PAH therapy on pulmonary hemodynamics in patients with POPH.Results.Sixteen patients were included. All patients were on PAH therapy at the time of LT. PAH therapy resulted in a decrease of mPAP (median 18.4%; interquartile range [IQR] 8.9%–27.0%) with a reduction in PVR (median 50.5%; IQR, 45.4%–70.7%), and an increase in both cardiac output (CO) (median 28.1%; IQR 5.7%–63.8%) and PAWP (median 50.0%; IQR 16.7%–108.3%) before LT. One year posttransplant survival was 69% (11/16); however, only 1 death was attributed to POPH. At 1-year posttransplant, 63.6% (7/11) of patients were weaned off all PAH therapy with clinical and echocardiographic resolution of POPH.Conclusions.In treated POPH patients with an mPAP ≥35 mm Hg and PVR < 250 dynes-s-cm−5 before LT, 1-year posttransplant survival was 69% and the majority of patients were able to discontinue PAH therapy.

CLINICAL CHARACTERISTICS, TREATMENT RESPONSE, AND SURVIVAL OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOSITIS AND PULMONARY ARTERIAL HYPERTENSION

CLINICAL CHARACTERISTICS, TREATMENT RESPONSE, AND SURVIVAL OF PATIENTS WITH IDIOPATHIC INFLAMMATORY MYOSITIS AND PULMONARY ARTERIAL HYPERTENSION

Особенности эндоваскулярного закрытия вторичного дефекта межпредсердной перегородки у больных старшего возраста

Aim. Secondary atrial septal defect (ASD II) is one of the most common congenital heart defects. While all the issues of endovascular correction of this disease in children and young patients have been practically resolved, many issues still remain debatable regarding the treatment of adult patients. In the proposed work, the author analyzes the main information’s discussed in the literature concerning this issue, such as the expediency and tactics of treatment of adult patients with ASD II, depending on its anatomical forms, the status of intracardiac and pulmonary-arterial hemodynamics, the presence of concomitant diseases. Materials and methods. The article presents a literature review based on the results of searching of publications in Russian and international bibliographic da-tabases (PubMed, eLIBRARY, Medscape, etc.). Results. Analysis of the literature data in most cases indicates the feasibility and high efficiency of endovascular closure of hemodynamically significant ASD II in elderly patients. The analysis of dynamic observations in the long term after endovascular treatment, reveals a decrease in MPAP as well as the size of the right heart. At the same time, compliance with certain rules makes the intervention quite safe, regardless of the age of patients and, to a certain extent, the severity of symptoms. In the literature, it is particularly emphasized that when determining the management tactics of adult patients with ASD II in order to prevent possible complications, should be objectively evaluated and taken into account such factors that determine their initial state as: the presence of high MPAP, volume overload of the right heart, and vice versa, underloading of the left heart, the conditions of the heart valves, the presence of arterial hypertension, existence of heart rhythm disorders, ischemic heart disease and left ventricle dysfunction. Conclusion. Modern medical literature convincingly proves that with the right selection of patients, transcatheter closure is a safe, highly effective method of correction of ASD II, accompanied by real economic effect and it should be considered a standard in the treatment of middle-aged and elderly patients. At the same time, studies on long-term results show that the positive functional effect does not have age restrictions.

Grape seed procyanidin suppresses inflammation in cigarette smoke-exposed pulmonary arterial hypertension rats by the PPAR-γ/COX-2 pathway

Background and aimPulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, which is mainly caused by inflammation. Inhibiting inflammation can relieve PAH. Grape seed procyanidin (GSP) possesses remarkable anti-inflammatory property and vascular protective function. In this experiment, we verified the anti-inflammatory property of GSP in cigarette smoke-exposed PAH rats and revealed its molecular mechanism. Methods and resultsIn vivo, 45 Sprague Dawley (SD) rats were divided into 5 groups randomly, treated with normoxia/cigarette smoke (CS)/GSP + CS/CS + solvent/GSP. After GSP + CS administration, a decrease in mPAP, PVR, RVHI, WT%, and WA% was detected in the rats as compared to those treated with CS. In vitro, the proliferation of pulmonary arterial smooth muscle cells (PASMCs) caused by cigarette smoke extract (CSE) was effectively attenuated with GSP + CSE administration. Furthermore, GSP significantly increased the expression of peroxisome proliferator-activated receptor γ (PPAR-γ) together with the lowered expression level of cyclooxygenase 2 (COX-2) in PASMCs co-incubated with CSE. ConclusionThese findings indicate that GSP ameliorates inflammation by the PPAR-γ/COX-2 pathway and finally inhibits the proliferation of PASMCs, which leads to pulmonary vascular remodeling.

Potts Shunt to Be Preferred Above Atrial Septostomy in Pediatric Pulmonary Arterial Hypertension Patients: A Modeling Study.

Aims: To quantitatively evaluate the basic pathophysiological process involved in the creation of Eisenmenger syndrome in pediatric pulmonary arterial hypertension (PAH) patients by either atrial septostomy (AS) or Potts shunt (PS) as well as to predict the effects of AS or PS in future PAH patients.Methods: The multi-scale lumped parameter CircAdapt model of the cardiovascular system was used to investigate the effects of AS and PS on cardiovascular hemodynamics and mechanics, as well as on oxygen saturation in moderate to severe PAH. The reference simulation, with cardiac output set to 2.1 l/min and mean systemic pressure to 61 mmHg, was used to create a compensated moderate PAH simulation with mPAP 50 mmHg. Thereupon we created a range of decompensated PAH simulations in which mPAP was stepwise increased from 50 to 80 mmHg. Then we simulated for each level of mPAP the acute effects of either PS or AS with connection diameters ranging between 0–16 mm.Results: For any mPAP level, the effect on shunt flow size is much larger for the PS than for AS. Whereas right ventricular pump work in PS is mainly dependent on mPAP, in AS it depends on both mPAP and the size of the defect. The effects on total cardiac pump work were similar for PS and AS. As expected, PS resulted in a drastic decrease of lower body oxygen saturation, whereas in AS both the upper and lower body oxygen saturation decreased, though not as drastically as in PS.Conclusion: Our simulations support the opinion that a PS can transfer suprasystemic PAH to an Eisenmenger physiology associated with a right-to-left shunt at the arterial level. Contrary to the current opinion that PS in PAH will decompress and unload the right ventricle, we show that while a PS does lead to a decrease in mPAP toward mean systemic arterial pressure, it does not unload the right ventricle because it mainly diverts flow from the pulmonary arterial system toward the lower body systemic arteries.

Grape seed proanthocyanidin reverses pulmonary vascular remodeling in monocrotaline-induced pulmonary arterial hypertension by down-regulating HSP70

Heat shock protein 70 (HSP70) is a molecular chaperone which has a low content in cytoplasm under normal physiological conditions. A higher intracytoplasmic HSP70 level can be observed in pulmonary arterial smooth muscle cell (PASMC) in pulmonary arterial hypertension (PAH), and this up-regulation can promote pho-IκBα expression, which is an NF-κB signaling pathway inhibitor. NF-κB signaling pathway up-regulation can promote PASMC proliferation and pulmonary vascular remodeling in PAH, resulting in elevation of pulmonary pressure and the subsequent right heart failure caused by right ventricular hypertrophy. Grape seed proanthocyanidin (GSP) is effective in vascular protection and several tumor treatments, and its effect on PAH treatment remains to be elucidated. In this study, we made observations and contrasts in monocrotaline(MCT) -induced PAH rats, and found decrease in mPAP, PVR and RVHI after GSP administration. Our study also proved GSP's effect on down-regulating the intracytoplasmic HSP70 content both in cellular and animal levels. The results indicate a possible mechanism of GSP reversing pulmonary vascular remodeling by down-regulating HSP70, and this change may influence pho-IκBα expression. Therefore, inhibition of NF-κB signaling pathway caused by GSP can lead to inhibition of PASMC proliferation in PAH.

Angiotensin-converting enzyme 2 activation ameliorates pulmonary endothelial dysfunction in rats with pulmonary arterial hypertension through mediating phosphorylation of endothelial nitric oxide synthase

This study aims to investigate the effect of angiotensin-converting enzyme 2 (ACE2) activation on pulmonary endothelial function in the process of preventing pulmonary arterial hypertension (PAH) in rat models and to explore the underlying mechanisms. Specific pathogen free rats were randomly divided into five groups including control group, PAH group, PAH + Resorcinolnaphthalein (Res) group (ACE2 activation), PAH + Res + MLN4760 group (ACE2 inhibition), and PAH + Res + L-NAME group (endothelial nitric oxide synthase [eNOS] inhibition). Rat PAH model was constructed using combined left pneumonectomy with a single dose of monocrotaline injection 1 week after the surgery, and the rats were then given corresponding reagents. Hemodynamics, endothelial function, and pathologic changes were evaluated 3 weeks after monocrotaline injection. The concentration of nitric oxide (NO), expression of eNOS, and phosphorylation of eNOS at Ser1177 and Thr495 in the lung tissues from rats were also investigated.The Res-induced activation of ACE2 led to decreased mean pulmonary arterial pressure (mPAP) and pulmonary artery remodeling in the PAH + Res group comparing with the PAH rats (P < .05). In addition, the reduction in mPAP induced by acetylcholine (Ach) was augmented in PAH + Res group (P < .05), but this was not observed under the treatment with sodium nitroprusside (SNP) (P > .05). The ratio of decrease in mPAP caused by Ach to that caused by SNP (Ach/SNP) was also increased (P < .05) in ACE2-activated rats. However, the protective effects of ACE2 activation on PAH were counteracted by co-administration of MLN4760, an ACE2 antagonist (all P > .05). The mechanistic study showed that the concentration of NO in the lung tissues was downregulated in the PAH group but upregulated in the PAH + Res group (P < .05), whereas the NO concentration in the PAH + Res + MLN4760 group was not obviously different from that in the PAH group (P > .05). Regarding the factors regulating NO release, we found that the eNOS was upregulated in the PAH group, and Res did not affect the expression of eNOS. The phosphorylation of eNOS at Ser1177 was increased but at Thr495 was reduced after Res injection, when compared with the PAH group (P < .05). As expected, co-injection of MLN4760 eliminated these differences (P > .05). The reduction in mPAP induced by Ach was attenuated in the PAH + Res + L-NAME group compared with the PAH + Res group (P < .05), but this was not observed in rats treated with SNP (P > .05). The Ach/SNP ratio of decline in mPAP was also decreased in the PAH + Res + L-NAME group (P < .05). Activation of ACE2 had a protective role in the development of PAH via improving the function of pulmonary arterial endothelium. This effect was potentially mediated by promoted NO release as a consequence of increased phosphorylation of eNOS at Ser1177 and dephosphorylation of eNOS at Thr495.

Acute hemodynamic effects of intravenous adenosine in patients with associated pulmonary arterial hypertension: Comparison with intravenous epoprostenol

Exogenous intravenous (IV) adenosine and epoprostenol are effective vasodilator agents, causing a substantial reduction in pulmonary vascular resistance in patients affected by idiopathic pulmonary arteriolar hypertension (PAH). Their action, in patients with PAH associated with other pathological conditions, is not well defined. In the present paper the authors retrospectively analyzed the acute hemodynamic effects of intravenous adenosine and epoprostenol in 30 consecutive patients (mean age: 58 ± 15 years; 21 females, and 9 males) affected by PAH associated with other pathological conditions, as determined by changes from baseline in systemic and pulmonary hemodynamic parameters.Acute IV administration of adenosine decreased pulmonary vascular resistance index (PVRI) by 3 Wood U/m2 (- 20%) compared to baseline (p = 0.02). We noted a slight, not significant, decrease in mean pulmonary artery pressure (mPAP) of 4 mmHg. Cardiac index (CI) increased by 0.5 L/min/m2 (15% increase respect to baseline; p = 0.03). The heart rate and mean systemic blood pressure (BP) did not change significantly. Acute IV administration of epoprostenol decreased PVRI by 6 mmHg (- 40%) respect to baseline (p < 0.0001). CI increased by 1.4 L/min/m2 (p < 0.0001); while mPAP decreased by 5 mmHg (nearly 10%) (p = 0.04). This decrease of mPAP was accompanied by a mean BP decrease of 11 mmHg compared to baseline (p = 0.003).Our results indicates that, in patients with PAH associated with other pathological conditions, adenosine is predominantly a positive inotropic agent; and epoprostenol a potent vasodilator of both pulmonary and systemic vessels, and a strong positive inotropic agent.