Pulmonary Vascular Resistance Levels Research Articles

Pulmonary vascular resistance/systemic vascular resistance (PVR/SVR) ratio changes after sildenafil therapy in uncorrected congenital heart disease-associated pulmonary arterial hypertension

Pulmonary vascular resistance (PVR) to systemic vascular resistance (SVR) ratio is a prognostic predictor in congenital heart disease (CHD)-associated pulmonary arterial hypertension (PAH) after defect correction. Sildenafil, widely used as a PAH drug, can decrease PVR with minimal or without changes in SVR, resulting in decreased PVR/SVR ratio after treatment. However, there is limited evidence that PVR/SVR ratio reduced after sildenafil therapy in uncorrected CHD-associated PAH patients. This study aimed to investigate the decreasing of the PVR/SVR ratio after ≥ 1-year oral sildenafil therapy in adult uncorrected CHD-associated PAH. A total of 30 uncorrectable CHD-associated PAH subjects derived from the COHARD-PH registry were included in this study. Right heart catheterization (RHC) was performed during the first visit and further evaluations were conducted after ≥1-year oral sildenafil therapy. The PVR/SVR ratio at the baseline and after the evaluation was collected. The primary outcome of this study was the changes in PVR/SVR ratio from baseline to evaluated RHC. Characteristic analysis of subjects with decreased PVR or PVR/SVR ratio was perforemd as the secondary outcome. The mean PVR and SVR were not different from baseline and evaluated RHC (15.98± 10.67 vs. 18.38±13.93 WU, p=0.206 and 36.65±13.99 vs. 39.34±15.46 WU, p=0.262). There was no significant difference in the baseline PVR/SVR ratio and the evaluated PVR/SVR ratio after ≥1-year sildenafil therapy (0.48 ±0.32 vs. 0.49±0.36; p=0.882). As much as 15 subjects (50%) experienced decreased PVR/SVR ratio. However, there was no significant difference in the characteristics, including age, Eisenmenger syndrome, type of shunts, baseline PVR, PAH-specific treatment, and baseline NT-proBNP level (p>0.05). In conclusion, sildenafil therapy does not change PVR/SVR ratio in adults with uncorrected CHD-associated PAH.

Mortality rates and cause of mortality in patients with mildly elevated pulmonary pressures versus PH: insights from the retrospective EVIDENCE-PAH study

Abstract Background Normal mean pulmonary artery pressure (mPAP) does not exceed 20 mmHg and normal pulmonary vascular resistance (PVR) does not exceed 2 Wood Units (WU). The thresholds used to define pre-capillary pulmonary hypertension (PH) – mPAP ≥25 mmHg and PVR >3 WU – are being evaluated. It is unclear if treatment would benefit patients with mildly elevated mPAP (≥21–<25 mmHg). Purpose The EVIDENCE-PAH study aims to describe mortality and hospitalisation outcomes, clinical characteristics, therapies, and quality of life during long-term follow-up of a national cohort of patients with different levels of mPAP and PVR. We report preliminary analyses focusing on mortality and its cause in patients stratified by their baseline (BL) mPAP. Methods This retrospective analysis included PAH-treatment-naïve patients with suspected PH who received a first right heart catheterisation (RHC) between 2009 and 2017 at any of the 7 UK tertiary PH centres, which assess all PH patients in the UK. A sample of patients with BL mPAP ≥25 mmHg (stratified by PVR and treatable versus non-treatable PH) was used as a control in this analysis. Baseline characteristics, mortality and cause of mortality were stratified by mPAP (<21, ≥21–<25, ≥25 mmHg) at BL (first RHC). Mortality was also stratified by BL PVR (<1, 1–<2, 2–<3, 3–<6, ≥6 WU). Mortality analysis was done without matching cohorts. Mortality data were obtained from the Office for National Statistics, NHS Digital. Results In total, 2926 patients were analysed (968, 689 and 1269 with mPAP <21, ≥21–<25, ≥25 mmHg, respectively). Mean observation was 6.1 years. BL characteristics are in Table. Survival worsened with increasing mPAP (p<0.0001) and increasing PVR (p<0.01) (Figure). After 5 years of follow-up, 187 (27.1%) patients with mPAP ≥21–<25 mmHg had died, compared with 162 (16.7%) and 595 (46.9%) patients in the lower and higher mPAP groups, respectively. In patients with mPAP ≥21–<25 mmHg, the most common main cause of death was respiratory disease (36.4%) – with scleroderma lung disease and interstitial lung disease accounting for 69.1% of these deaths – followed by cardiac disease (16.6%) and malignancy (15.0%) (Table). PH was the main cause of death for only 1.6% of patients with mildly elevated mPAP and it was a contributor to death in 6.8% (BL mPAP <21 mmHg), 10.2% (≥21–<25 mmHg), and 40.2% (≥25 mmHg) of cases. Conclusion Long-term survival in patients with mPAP ≥21–<25 mmHg was worse than in those with normal mPAP, and better than in those with the current definition of PH. While the main cause of death was mostly unrelated to PH and further analysis is needed to understand the impact of underlying disease, mildly elevated mPAP appears to confer a worse prognosis and should be closely monitored. These data show the relevant disease burden in patients with mPAP ≥21–<25 mmHg and the need to understand if they could benefit from treatment. PVR may be key in determining patients who might benefit. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Actelion Pharmaceuticals Ltd., a Janssen pharmaceutical company of Johnson & Johnson.

Prognostic impact of follow-up pulmonary vascular resistance in pulmonary arterial hypertension

ObjectivePulmonary arterial hypertension (PAH), caused by pulmonary artery remodelling and increased pulmonary vascular resistance (PVR) due to an unknown mechanism, is an intractable disease with a poor prognosis. The recent...

Clinical Efficacy of Budesonide/Glycopyrronium Bromide/Formoterol in the Treatment of Patients with Acute Respiratory Distress Syndrome and Its Effect on Inflammatory Factors.

Objective To examine the clinical efficacy of budesonide/glycopyrronium bromide/formoterol (Breztri Aerosphere) as an adjunct to acute respiratory distress syndrome (ARDS). Methods A prospective study enrolled 120 patients with pulmonary endogenous ARDS admitted to the Department of Critical Care Medicine at the Fourth Hospital of Baotou from January 2017 to January 2020, and all enrollments were assigned (1 : 1) to receive conventional treatment (control group) or Breztri Aerosphere (study group). Results Breztri Aerosphere was associated with a significantly higher total efficacy versus conventional treatment. Breztri Aerosphere resulted in significantly lower acute physiology and chronic health evaluation scoring system (APACHE II) scores and Murray lung injury scores versus conventional treatment. Both groups saw an increase in the partial pressure of carbon dioxide (PCO2), partial pressure of oxygen (PO2), and oxygen saturation (SaO2) after treatment, with higher levels seen in patients given Breztri Aerosphere. After treatment, systemic vascular resistance (SVR) in both groups rose markedly, with greater elevation witnessed in the study group. The patients given Breztri Aerosphere showed significantly lower levels of pulmonary vascular resistance (PVR), mean pulmonary arterial pressure (MAPA), pulmonary artery wedge pressure (PAWP), interleukin-6 (IL-6), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and procalcitonin (PCT) versus those receiving conventional treatment. The patients experienced shorter mechanical ventilation time and intensive care unit (ICU) time after treatment of Breztri Aerosphere versus conventional treatment. Conclusion Adjuvant therapy with Breztri Aerosphere in ARDS can significantly lower APACHE II scores and Murray lung injury scores, improve blood gas indexes and pulmonary circulation function indexes, and shorten mechanical ventilation time and ICU time, which may be attributed to its improvement of organism inflammation status and reduction of inflammatory factors.

Plasma exosomal miR-596: a novel biomarker predicts survival in patients with idiopathic pulmonary artery hypertension.

ObjectiveTo determine if plasma exosomal microRNAs (miRNAs) can predict survival in patients with idiopathic pulmonary arterial hypertension (IPAH).MethodsThe study enrolled patients with IPAH that underwent right heart catheterization. Plasma was collected and exosomal miRNAs were extracted. Exosomes were evaluated using transmission electron microscopy, Western blot analysis and particle size distribution analysis. MiRNAs were evaluated using a miRNA microarray and validated using real-time polymerase chain reaction.ResultsThis study included 12 patients with IPAH in the study group and 48 patients with IPAH in the validation group. The mean ± SD follow-up duration was 60.3 ± 35.4 months in the overall cohort. The levels of miR-596 were higher in the nonsurvivors compared with the survivors. The levels of miR-596 significantly correlated with survival time, mean right atrial pressure, pulmonary vascular resistance (PVR) and cardiac index. High levels of miR-596 and PVR were significantly associated with poor overall survival. Multivariate analysis demonstrated that exosomal miR-596 (hazard ratio [HR] = 2.119; 95% confidence interval [CI] 1.402, 3.203) and PVR (HR = 1.146; 95% CI 1.010, 1.300) were independent predictors of survival.ConclusionsHigh levels of plasma exosomal miR-596 were significantly associated with disease severity and poor prognosis of patients with IPAH.

Results of pulmonary thromboendarterectomy depending on different levels of pulmonary vascular resistance and angiographic index of the pulmonary artery lesion

Objective. Pulmonary endarterectomy is a first-choice treatment for patients with chronic thromboembolic pulmonary hypertension. Data describing the results of the operation with different levels of pulmonary vascular resistance (PVR) depending on the spread and percentage of pulmonary artery disease are not declared in the world literature. The aim of our study is to evaluate and compare the hospital results of the operation in patients with different levels of pulmonary vascular resistance, depending on the CT-angiographic index of the pulmonary artery lesion.
 Materials and methods. A retro-prospective study was conducted, which included 52 patients. All patients were divided into 2 groups, depending on the levels of pulmonary vascular resistance (PVR): group 1 included 31 patients with PVR1000 dynes/cm5, group 2 21 patients with PVR1000 dynes/cm5. Data of the preoperative right heart catheterization in groups 1 and 2, respectively: mean pulmonary artery pressure (mPAP) 44.48.3 and 56.99.6 mm Hg, pulmonary artery wedge pressure 7.32.4 and 61.5 mm. Hg, cardiac output (CO) 3.90.9 and 3.20.6 l/min, cardiac index (CI) 20.5 and 1.60.4 l/min/m2, PVR 767174 and 1272.6186.4 dynsec/cm5. The operation was carried out bilaterally according to a standard protocol with cardiopulmonary bypass, deep hypothermia and circulatory arrest.
 Results. Data of the right heart catheterization on the first day after the operation in first and second groups, respectively: mPAP 28.56.3 and 35.784.2 mm Hg, PVR 253.3985.5 and 333.9101.9 dynes/cm5, CO 5.370.9 and 5, 21.1 l/min, CI 2.690.39 and 2.60.4 l/min/m2. There was a significant decrease of pulmonary hypertension (p0.05) in the early postoperative period, in both groups. However, a detailed analysis of the obtained data revealed that in patients with pulmonary vascular resistance of more than 1000 dynes/cm5 with a pulmonary artery lesion index of less than 50%, a significant course of the early postoperative period along the combined endpoint was observed. The intensive care unit stay was 4 days in average in both groups. The need for a tracheostomy for the prolongation of artificial ventilation of the lungs was in 2 and 1 cases in first and second groups, respectively. In the first group, there were 5 cases of transient neurological disorders, which regressed at the time of discharge. Two patients in the second group died.
 Conclusion. Despite the varying levels of baseline PVR, a significant improvement in hemodynamic parameters is observed in the early postoperative period, although patients in group 2 were less proven to normalization of pulmonary hemodynamics. However, a detailed comparative analysis revealed that the most severe category of patients are patients with PVR1000 dynes/cm5, with pulmonary artery lesion index of less than 50%. Thus, the calculation of the CT-angiographic index of pulmonary artery diseases an additional diagnostic method to rate the risks of surgery, especially in patients with a high level of preoperative pulmonary hypertension

Efficacy and safety of Balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

Objective: To study the efficacy and safety of Balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: Patients who were diagnosed CTEPH in China-Japan Friendship Hospital from Feb 2018 to Sep 2019 were evaluated. The ineligibility for pulmonary endarterectomy (PEA) and the indication for BPA were decided on the basis of a consensus among the multidisciplinary team for all CTEPH patients. 6-min walk distance (6MWD), the plasma level of N-terminal pro-brain natriuretic peptide (NT-proBNP), mixed venous oxygen saturation, mean pulmonary artery pressure (mPAP), cardiac index (CI) and pulmonary vascular resistance (PVR) were collected and analyzed before the first and the last BPA session. Results: A total of 67 BPA sessions were performed for 302 subsegmental pulmonary arteries in 25 inoperable CTEPH patients. 10 males (40.0%) and 15 females (60.0%), with the age of (57.8±7.1) years old. The median interval between CTEPH diagnosis and first BPA was 20.0 (9.0, 48.5) months. 18 patients were received more than 2 BPA sessions, the median follow-up time was 5.0 (3.5, 8.3) months. 6MWD, CI and the mixed venous oxygen saturation were significant improved after BPA [(425±74) vs (345±109) m, (1.99±0.45) vs (1.62±0.35) L·min(-1)·m(-2), (68.1%±6.5%) vs (61.2%±6.3%)](all P<0.05). The plasma level of NT-proBNP, mPAP and PVR were significantly decreased after BPA [259 (93, 739) vs 806 (148, 2 159) ng/L, (40.6±8.3) vs (47.3±10.7) mmHg (1 mmHg=0.133 kPa), (11.9±4.9) vs (17.2±6.5) WU (1 WU=80 dyn·s·cm(-5))](all P<0.05). Hemoptysis occurred in 5 sessions (7.5%) and reperfusion pulmonary edema (RPE) occurred in 2 sessions (1.5%), 1 patient needed non-invasive mechanical ventilation because of RPE, 1 patient died from right heart failure caused by hemoptysis during perioperative period. Conclusions: BPA can significantly improve the exercise tolerance and hemodynamic parameters for inoperable CTEPH patients, the risks of BPA are acceptable. BPA is an effective and relatively safe treatment for inoperable CTEPH patients.

Baseline pulmonary hypertension in heart transplant recipients: 9 years of experience at Almazov National Medical Research Centre

Objective: to assess the impact of baseline pulmonary hypertension (PH) on early and long-term outcomes following heart transplantation (HT). Materials and methods. From January 2010 to December 2018, 112 HTs were carried out. Based on right heart catheterization results, all recipients were divided into 2 groups: Group 1 with PH (n = 76; mean pulmonary arterial pressure (mPAP) ≥25 mm Hg), Group 2 – without PH (n = 36; MPAP &lt;25 mm Hg). The average age of Group 1 patients was 46.4 ± 14.9 years, baseline pulmonary vascular resistance (PVR) was 3.5 ± 1.5 Wood units, PVR after reversion test (nitric oxide – 80 ppm, iloprost 20 μg) – 2.8 ± 1.0 Wood units, systolic PAP (sPAP) – 50.1 ± 13.4 mm Hg. The average age in Group 2 was 47.3 ± 12.2 years, baseline PVR – 2.1 ± 0.8 Wood units, sPAP – 27.4 ± 5.3 mm Hg. The dynamics in indicators of early postoperative period (duration of mechanical ventilatory support, use of vasodilators and inotropic support and the length of stay in intensive care unit (ICU), 30-day mortality) and long-term post-HT echocardiography results were assessed. Results. Due to acute right-ventricular failure (RVF) developing after heart transplantation, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was done in 8 patients (11%) from Group 1 and one patient (3%) from Group 2. Presence of PH did not affect duration of mechanical ventilatory support, inotropic support, and length of stay in ICU. Levosimendan therapy in the early postoperative period was more often performed in Group 1 (n = 29) than in Group 2 (n = 6) (p = 0.048). Nitric oxide inhalation was also more often administered in Group 1 (n = 54); Group 2 (n = 7), (p = 0.003). Sildenafil therapy after HT was comparable in both groups Group 1 (n = 25); Group 2 (n = 6), (p = 0.048). In early post-HT stages, 14 patients died, 30-day mortality was comparable in both groups (p = 0.12). Six months after HT, no differences were found in the sPAP (p = 0.21) and PVR (p = 0.07) levels. Conclusion. Patients with baseline PH after HT have a more severe early postoperative period, including a higher RVF incidence, with the need for ECMO implantation. A PVR level &gt;3.5 Wood units is not a threshold for HT. Patients with baseline PVR &gt;3.5 Wood units following HT show comparable results with patients without baseline PH. This allows such patients (baseline PVR &gt;3.5 Wood units) to be considered for inclusion in the heart transplant waiting list. In addition, 30-day mortality and duration of mechanical ventilatory support after HT in patients with and without baseline PH did not differ. Regardless of the baseline level of sPAP and PVR, all patients showed improvement in these parameters after HT. Six months after HT, no differences were found in sPAP and PVR levels in the patients, regardless of whether there was baseline PH or not.

Clinical characteristics of patients with chronic thromboembolic pulmonary hypertension

Objective: To investigate the clinical characteristics of patients with chronic thromboembolic pulmonary hypertension (CTEPH). Methods: CTEPH cases consecutively admitted into China-Japan Friendship Hospital from September 2015 to June 2019 were enrolled with prospective data collection. The medical histories, clinical characteristics, laboratory tests, imaging manifestation and hemodynamic parameters were analyzed. Patients were divided into high pulmonary vascular resistance (PVR) group and low PVR group according to the PVR level>1 000 dyn·s·cm(-5) or not, and clinical characteristics were compared between these two groups. Results: In the 148 cases of CTEPH, right heart catheterization was performed in 103 cases with mPAP (45.1±11.0) mmHg and PVR of (992±430) dyn·s·cm(-5). At diagnosis, 88 (59.5%) cases were in WHO functional class Ⅲ and 27 (18.2%) in class Ⅳ. Most common presenting symptoms were dyspnea (147, 99.3%), chest tightness (68, 45.9%), hemoptysis (42, 28.3%), syncope (30, 20.3%), and most common signs were P2 accentuation (95, 64.9%), edema (65, 43.9%), cyanosis (47, 31.8%), systolic murmur (44, 29.7%) and jugular vein distention (35, 23.6%). In 103 cases with right heart catheterization, 52 were in the low PVR group and 51 in high PVR group. Compared to the low PVR group, high PVR group patients had higher WHO functional class and more jugular vein distention (both P<0.05). In all the 148 cases, previous venous thromboembolism (VTE) was confirmed in 105 (70.9%) patients, with a higher prevalence of previous VTE in low PVR group than that in high PVR group (P<0.001). 30 (20.3%) patients had varicose veins of the lower extremities, and 21 (14.2%) had other thrombophilic disorders including antiphospholipid syndrome, protein C and S deficiency and antithrombin Ⅲ deficiency. Conclusions: Dyspnea, P2 accentuation and edema are the most common clinical presentation of CTEPH. Previous history of VTE is common in CTEPH patients with thrombophilia in some cases.

P4690Effects of pulmonary artery wedge pressure on right ventricular pulsatile loading in pulmonary hypertension: a reappraisal based on pulmonary arterial isobaric stiffness

Abstract Background Pulmonary hypertension (PH) is associated with stiffening of pulmonary arteries. Previous studies have suggested that high pulmonary artery wedge pressure (PAWP) in postcapillary PH (Pc-PH) further augments PA stiffness at a given level of pulmonary vascular resistance as compared to pulmonary arterial hypertension (PAH). However, these studies do not take into account differences in distending pressure (mean PA pressure, mPAP), which has an effect on stiffness due to non-linear stress-strain behavior of arteries. Purpose To compare total PA stiffness between Pc-PH and idiopathic PAH (iPAH) studied at similar mPAP (isobaric stiffness). Methods This was an analysis of right heart catheterization results obtained in 112 Pc-PH and 112 iPAH patients extracted from the French PAH network registry and matched for mPAP (median 38 vs 39 mmHg, P=NS), age (70.5 years each) and sex (64% female each). Total PA stiffness was calculated as the ratio of PA pulse pressure to indexed stroke volume. Results Total PA stiffness (n=224) increased with mPAP (Spearman's rho = 0.66) and decreased with PAWP (rho = - 0.17) (each P&lt;0.01). The isobaric stiffness was lower in Pc-PH (median (IQR) = 0.91 (0.64–1.39) mmHg/mL/m2) than in iPAH (1.18 (0.83–1.62) mmHg/mL/m2, P&lt;0.01). The patients were then stratified according to their mPAP (25–35 mmHg, n=74 (37/37); 36–43 mmHg, n=75 (34/41); and 44–66 mmHg, n=75 (41/34)). The isobaric stiffness was lower in Pc-PH than iPAH in the 1st mPAP tertile (0.62 vs 0.83 mmHg/mL/m2, P=0.06), in the 2nd mPAP tertile (0.76 vs 1.22 mmHg/mL/m2, P&lt;0.01) and in the 3rd mPAP tertile (1.41 vs 1.77 mmHg/mL/m2, P&lt;0.01). The pulmonary vascular resistance was lower in Pc-PH than iPAH in every mPAP tertile (each P&lt;0.01). Finally, Pc-PH had a higher indexed stroke volume than iPAH (37 (29–48) vs 32 (27–40) mL/m2, P&lt;0.01) while systolic PA pressure and PA pulse pressure were similar. Conclusion Unexpectedly, the isobaric pulmonary arterial stiffness was lower in Pc-PH than iPAH patients. It is proposed that PAWP attenuates the increase in RV pulsatile loading in PH when the natural high-strain-induced stiffening was accounted for. This may contribute to a less impaired right ventricular-PA coupling leading to higher indexed stroke volume in Pc-PH than iPAH despite similar PA pressure. At every mPAP level, both the lower PA stiffness and lower pulmonary vascular resistance in Pc-PH than in iPAH may contribute to explain differences in the pressure overload-induced right ventricular adaptation between the two diseased groups, a point that deserves to be confirmed by further studies. Acknowledgement/Funding University regular funds

Early Treatment of Pulmonary Arterial Hypertension: Is a PVR > 3 Threshold too High?

Introduction: A pulmonary vascular resistance (PVR) criterion of >3 Wu was introduced into the haemodynamic definition of pulmonary arterial hypertension (PAH) in 2013. Lower levels of PVR can be abnormal, particularly in the younger population. There is limited data on the natural history and response to PAH therapy in patients with precapillary pulmonary hypertension with PVR <3 Wu. Methods: Using the PHSANZ registry, we analysed outcomes of all patients fulfilling the haemodynamic criteria: mPAP ≥25 mmHg, PAWP ≤15 mmHg and PVR <3 Wu. Patients with left-to-right cardiac shunts, chronic liver, lung, and left heart disease were excluded. Results: 82 patients (mean age 63 ± 11 years, 82% female) were included. Underlying diagnosis included idiopathic (n = 39), connective tissue disease (n = 42) and HIV infection (n = 1). At diagnosis, haemodynamics showed mPAP 28 ± 4 mmHg, PAWP 12 ± 2 mmHg and PVR 2.3 ± 0.5 Wu. Baseline exercise capacity revealed mean 6MWD of 341 ± 124 m with 77% in NYHA FC 3/4. All patients were commenced on initial monotherapy with endothelin receptor antagonists (n = 66) or phosphodiesterase type 5 inhibitors (n = 16). At first post-treatment evaluation (median 5 months; IQR 4-12), 6MWD increased by 46 m (IQR 7-96) and 35% demonstrated improvement in NYHA FC status. After a median follow-up of 65 months (IQR 32-101), 22% were deceased, with estimated 1-yr, 3-yr and 5-yr survivals of 98%, 88%, 84%, respectively. Conclusions: Our data suggest that selected patients with precapillary PH with PVR <3 Wu may benefit from PAH therapy. Further studies are needed to determine whether early treatment of these patients confers beneficial impact on exercise capacity and outcomes.

Study of hemodynamics during cardiac arrest and after restoration of spontaneous circulation in a porcine cardiac arrest model induced by acute pulmonary embolism

Objective To observe the hemodynamic change during cardiac arrest (CA) and after restoration of spontaneous circulation (ROSC) in a porcine acute pulmonary embolism model. Methods A total of 14 inbred Beijing Landraces were used to estalish the model of CA and ROSC induced by acute pulmonary embolism through injection of thrombus followed by cardiopulmonary resuscitation and thrombolytic therapy (urokinase, 15 000 U/kg, iv). Five resuscitated pigs restored spontaneous circulation. Hemodynamic changes were determined at baseline, CA, ROSC, and 0.5, 1, 1.5, 2, 2.5, 4, and 6 h after ROSC. Results Compared with the baseline, mean arterial pressure was decreased significantly, mean pulmonary arterial pressure and right ventricular pressure were increased significantly, and the heart rate had no change during CA induced by acute pulmonary embolism. The mean arterial pressure restored normal level gradually after ROSC, but was decreased at 4 h after ROSC compared with the baseline (P<0.05). The heart rate was faster at ROSC and 0.5-2 h after ROSC than the baseline (P<0.05). The mean pulmonary arterial pressure restored the baseline level after ROSC; The right ventricular pressure were decreased at 2.5 h (26.5±11.4) mmHg and 4 h (24.8±9.3) mmHg after ROSC compared with the level during CA (46.2±13.01) mmHg (P<0.05). The systemic vascular resistance peaked at 4 h after ROSC. The pulmonary vascular resistance level at ROSC was higher than the baseline [(96.5±24.8)DS/cm5vs. (26.5±13.4)DS/cm5, P<0.05], and was decreased at 1 h and 2 h after ROSC, but was increased at 4 h and 6 h after ROSC [(98.5±0.7)DS/cm5 and (98.0±1.4)DS/cm5]. The changes of heart function: compared with the baseline, the left ventricular function at ROSC and 1-6 h after ROSC were declined significantly (all P<0.05), and right cardiac output declined at ROSC and 4 h and 6 h after ROSC (all P<0.05), and the level of cardiac function index was dropped at 1 h and 2 h after ROSC (P<0.05). Conclusions The mean arterial pressure was declined, mean pulmonary arterial pressure, right ventricular pressure and pulmonary vascular resistance were increased, cardiac function was decreased during CA induced by acute pulmonary embolism; After ROSC, hemodynamic changes were described as compensated in the early stage (1-2 h after ROSC) and decompensated (4 h after ROSC) with time. Key words: Acute pulmonary embolism; Pig; Cardiac arrest; Restoration of spontaneous circulation; Hemodynamics

Hematocrit-corrected Pulmonary Vascular Resistance.

The diagnosis and evaluation of severity of pulmonary vascular disease rests on the invasive determination of a pulmonary vascular resistance (PVR). It is often overlooked that PVR is linearly related to the viscosity of the blood, which in turn is curvilinearly related to hematocrit. We propose a correction diagram for patients with anemia or with polycythemia. Based on a distensibility model of the pulmonary circulation, we show that magnitude of hematocrit correction of PVR is increased in proportion to pulmonary artery wedge pressure (PAWP) and the measured levels of PVR or hematocrit, and decreased in case of preserved resistive vessel distensibility and absence of pulmonary hypertension. We also demonstrate that hematocrit correction of PVR is independent of the absolute levels of pulmonary artery pressure or cardiac output. A PVR of 1.5 Wood units (WU) at a hematocrit of 20 % and a high-normal PAWP becomes 4.1 WU at a hematocrit of 45 % and 10.8 WU at a hematocrit of 80 %. A review of reported hemo...

Three-Dimensional Echocardiography for the Assessment of Right Ventriculo-Arterial Coupling

The analysis of right ventriculo-arterial coupling (RVAC) from pressure-volume loops is not routinely performed. RVAC may be approached by the combination of right heart catheterization (RHC) pressure data and cardiac magnetic resonance (CMR)-derived right ventricular (RV) volumetric data. RV pressure and volume measurements by Doppler and three-dimensional echocardiography (3DE) allows another way to approach RVAC. Ninety patients suspected of having pulmonary hypertension underwent RHC, 3DE, and CMR (RHC mean pulmonary artery pressure [mPAP] 37.9±11.3mm Hg; range, 15-66mm Hg). Three-dimensional (3D) echocardiography was performed in 30 normal patients (echocardiographic mPAP 18.4±3.1mm Hg). Pulmonary artery (PA) effective elastance (Ea), RV maximal end-systolic elastance (Emax), and RVAC (PAEa/RV Emax) were calculated from RHC combined with CMR and from 3DE using simplified formulas including mPAP, stroke volume, and end-systolic volume. Three-dimensional echocardiographic and RHC-CMR measures for PA Ea (3DE, 1.27±0.94; RHC-CMR, 0.71±0.52; r=0.806, P<.001), RV Emax (3DE, 0.72±0.37; RHC-CMR, 0.38±0.19; r=0.798, P<.001), and RVAC (3DE, 2.01±1.28; RHC-CMR, 2.32±1.77; r=0.826, P<.001) were well correlated despite a systematic overestimation of 3DE elastance parameters. Among the whole population, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax were significantly lower in patients with mPAP < 25mm Hg (n=41) than in others (n=79). Among the 90 patients who underwent RHC, 3D echocardiographic PA Ea and 3D echocardiographic RVAC but not 3D echocardiographic RV Emax increased significantly with increasing levels of pulmonary vascular resistance. Three-dimensional echocardiography-derived PA Ea, RV Emax, and RVAC correlated well with the reference RHC-CMR measurements. Ea and RVAC but not Emax were significantly different between patients with different levels of afterload, suggesting failure of the right ventricle to maintain coupling in severe pulmonary hypertension.

Echocardiographic evolution of pulmonary hypertension in female patients with hyperthyroidism.

Objective:The objective of this study was to highlight the impact of increased cardiac output (CO) and/or pulmonary vascular resistance (PVR) on the occurrence and evolution of pulmonary hypertension (PH) in hyperthyroidism and to follow their evolution in patients under therapy.Methods:Our study group consisted of 142 women with hyperthyroidism of different severities and etiologies. We divided our patients into three groups: groups A (overt hyperthyroidism), B (recurrent disease), and C (subclinical forms). We performed echocardiography to determine echocardiographically estimated systolic pulmonary arterial pressure (eePAP), CO, and PVR before and at 3, 6, and 12 months after treatment with thyroid suppression therapy and beta-blockers.Results:In our study group we documented PH of various severities in 73 patients (51.4%). Increased CO, induced mostly by hyperthyroidism-specific tachycardia, was frequently detected in overt hyperthyroidism and also augmented PVR, as documented in 43.66% of patients with severe and recurrent forms. For all patients with PH, we emphasized a strong correlation between eePAP and PVR level (r=0.854, p<0.0001) and a moderate one with CO (r=0.437, p<0.0001) and with hyperthyroidism duration (r=0.545, p<0.0001). Under therapy, CO rapidly normalized and PVR significantly decreased in groups A and C. In group B, the reduction was modest and statistically significant.Conclusion:The pathophysiological mechanisms responsible for the occurrence of PH are elevated CO and PVR. While increased CO is rapidly alleviated under therapy, elevated eePAP and PVR persist in recurrent cases and are responsible for the perpetuation of PH.

N-terminal pro–B-type natriuretic peptide for monitoring after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

Balloon pulmonary angioplasty (BPA) is an emerging interventional treatment option for chronic thromboembolic pulmonary hypertension (CTEPH). The non-invasive monitoring of CTEPH patients is a clinical challenge. In this study we examined changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients undergoing BPA for inoperable CTEPH and related them to peri-procedural success. In this study we analyzed a total of 51 consecutive patients who underwent BPA treatment and completed a 6-month follow-up (6-MFU) between March 2014 and March 2017. Serum samples for NT-proBNP measurement were collected before every BPA and at 6-MFU. The 51 patients underwent 265 interventions involving angioplasty of a total of 410 vessels. The 6-month survival rate was 96.1%. The baseline (BL) mean pulmonary artery pressure (PAP) was 39.5 ± 12.1 mm Hg, pulmonary vascular resistance (PVR) was 515.8 ± 219.2 dynes/s/cm5 and the median NT-proBNP level was 820 (153 to 1,871.5) ng/liter. At BL, World Health Organization functional class (FC) was ≥III in 96.1% of the patients, whereas, at 6-MFU, 11.8% were in WHO FC ≥III. At 6-MFU, mean PAP (32.6 ± 12.6 mm Hg; p < 0.001), PVR (396.9 ± 182.6 dynes/s/cm5; p < 0.001) and NT-proBNP (159.3 [84.4 to 464.3] ng/liter; p < 0.001) levels were reduced. The decrease in NT-proBNP levels correlated with the decrease in mean PAP (rrs = 0.43, p = 0.002) and PVR (rrs = 0.50, p = 0.001). A reduction in the NT-proBNP level of 46% indicated a decrease in mean PAP of ≥25% (area under the curve [AUC] = 0.71) and a reduction of 61% indicated a decrease in PVR of ≥35% (AUC 0.77). Our results demonstrate that NT-proBNP levels decrease after BPA, providing valuable evidence of procedural success. NT-proBNP measurement allows identification of patients who are BPA non-responders and may thus be a valuable adjunct in therapy monitoring.

The impact of alteplase on pulmonary graft function in donation after circulatory death - An experimental study.

ObjectiveLung transplantation is hampered by the lack of organs resulting in deaths on the waiting list. The usage of donation after circulatory death (DCD) lungs would dramatically increase donor availability. The most optimal organ preservation method, and the need for antithrombotic and fibrinolytic treatment to prevent thrombosis in the donor lungs is currently on debate. The present study investigated, in a simulated clinical DCD situation, whether the addition of alteplase in the flush-perfusion solution at the time of pulmonary graft harvesting could prevent thrombosis in the donor lung and thereby improve pulmonary graft function.MethodsTwelve Swedish domestic pigs were randomized into two groups. All animals underwent ventricular fibrillation and were then left untouched for 1 h after declaration of death. None of the animals received heparin. The lungs were then harvested and flush-perfused with Perfadex® solution and the organs were then stored at 8 °C for 4 h. In one group alteplase was added to the Perfadex® solution (donation after cardiac death with alteplase (DCD-A)) and in the other, it was not (DCD). Lung function was evaluated, using ex vivo lung perfusion (EVLP), with blood gases at different oxygen levels, pulmonary vascular resistance (PVR), lung weight, and macroscopic appearance.ResultsDuring EVLP, there were no significant differences between groups in PaO2 at any investigated FiO2 level (1.0, 0.5, or 0.21). At FiO2 1.0, the PaO2 in the DCD and DCD-A was 51.7 ± 2.05 kPa and 60.3 ± 3.67 kPa, respectively (p = 0.1320). There were no significant differences between groups PVR levels, in the DCD (372 ± 31 dyne x s/cm5) and in the DCD-A (297 ± 37 dyne x s/cm5) groups (p = 0.1720). There was no significant difference between groups in macroscopic appearance.ConclusionsAll the lungs showed excellent blood gases after EVLP, and they all meet the criteria's for clinical lung transplantation. The use of alteplase did not seem to have any obvious benefit to the donor lungs in a DCD situation. The donor lungs treated with alteplas showed slightly better blood gases and slightly lower PVR compared to the group without alteplas, however the difference was not significant. DCD appears to be a safe and effective method to expand the donor pool.

Clinical significance of mechanical ventilation on ischemic-reperfusion injury caused by lung chest trauma and VEGF expression levels in peripheral blood.

We investigated the clinical significance of mechanical ventilation on ischemic-reperfusion injury caused by lung chest trauma as well as vascular endothelial growth factor (VEGF) expression levels in peripheral blood. Sixty-eight patients with severe chest trauma complicated with acute respiratory distress syndrome that were treated at our Tianjin Hospital from September 2013 to July 2016 were recruited. These patients were randomly and evenly divided into two groups, the research group and the control group. Thirty-four age and gender matched healthy people were selected as the normal group. Routine treatment was given to both the research and control groups, but mechanical ventilation was used in the research group. We detected pulmonary vascular resistance (PVR) and alveolar-arterial oxygen difference (AaDO2) for patients in both groups before treatment, and after treatment for 1, 3, 6 and 12 h. We also tested PMN, superoxide dismutase (SOD), malondialdehyde (MDA), NO and Ang II value 30 min before and after treatment. We used the ELISA-test to detect VEGF expression levels in peripheral blood, followed by a statistical analysis. PVR levels of different time points in the research group were significantly lower than control group after treatment. The AaDO2 value of the control group is much smaller than research group (P<0.5) after treatment for 1, 3 or 6 h. PMN count difference and MDA level in the research group is significantly lower than the control group after treatment for 30 min, but SOD and NO levels are much higher. Ang II levels of the research group in left atrial blood is significantly lower than control group (P<0.05). By comparing the hospitalization times, we found that patients in the research group have a shorter duration in hospital than the control group; differences are statistically significant (P<0.05). Additionally, compared to control group, research group VEGF expression levels in peripheral blood are significantly lower (P<0.05). Therefore, mechanical ventilation can reduce the high VEGF expression levels in serum caused by ischemic-reperfusion and can be used for clinical application.

Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension

Background and objectivePulmonary thromboendarterectomy surgery is the treatment of choice for patients with chronic thromboembolic pulmonary hypertension; extremely high pulmonary vascular resistance constitutes a risk factor for hospital mortality. The objective of this study was to analyze the immediate and long-term results of the surgical treatment of chronic thromboembolic pulmonary hypertension in patients with very severe pulmonary hypertension. Material and methodsSince February 1996, we performed 160 pulmonary thromboendarterectomies. We divided the patient population in 2 groups: group 1, which included 40 patients with pulmonary vascular resistance≥1090dyn/s/cm−5, and group 2, which included the remaining 120 patients. ResultsHospital mortality (15 vs. 2.5%), reperfusion pulmonary edema (33 vs. 14%) and heart failure (23 vs. 3.3%) were all higher in group 1; however, after one year of follow-up, there were no significant differences in the clinical, hemodynamic and echocardiographic conditions of both groups. Survival rate after 5 years was 77% in group 1 and 92% in group 2 (p=0.033). After the learning curve including the 46 first patients, there was no difference in hospital mortality (3.8 vs. 2.3%) or survival rate after 5 years (96.2% in group 1 and 96.2% in group 2). ConclusionsPulmonary thromboendarterectomy is linked to significantly higher morbidity and mortality rates in patients with severe chronic thromboembolic pulmonary hypertension. Nevertheless, these patients benefit the same from the procedure in the mid-/long-term. In our experience, after the learning curve, this surgery is safe in severe pulmonary hypertension and no level of pulmonary vascular resistance should be an absolute counter-indication for this surgery.

Pulmonary hypertension due to left heart disease: analysis of survival according to the haemodynamic classification of the 2015 ESC/ERS guidelines and insights for future changes.

Pulmonary hypertension (PH) is a relevant complication of left heart disease (LHD). The 2015 ESC/ERS PH guidelines report two different haemodynamic subsets of PH due to LHD (PH-LHD) based on levels of pulmonary vascular resistance (PVR) and diastolic pressure gradient (DPG): isolated post-capillary PH (Ipc-PH) and combined post- and pre-capillary PH (Cpc-PH). The objective of this study is to evaluate the prognostic value of Ipc-PH and Cpc-PH. Data from 276 consecutive incident patients with PH-LHD were included. According to the guidelines, Ipc-PH is defined by DPG <7 mmHg and/or PVR ≤3 Wood units (WU) and Cpc-PH by DPG ≥7 mmHg and/or PVR >3 WU. Using this definition, we identified three patient groups: Ipc-PH with both normal PVR and DPG (108 patients); Cpc-PH with both increased PVR and DPG (66 patients); and an intermediate group with either increased PVR or DPG (102 patients). Survival was estimated using the Kaplan-Meier method and compared between groups using the log-rank test. Patients with Ipc-PH had better survival compared with the group of patients with Cpc-PH (P = 0.026) and the intermediate group (P = 0.025). No survival difference was detected between patients with Cpc-PH and the intermediate group (P = 0.891). Patients with normal PVR had a better survival compared with those with elevated PVR (P = 0.012); while no difference was observed according to the level of DPG (P = 0.253). Patients with Ipc-PH have a better prognosis compared with patients with Cpc-PH and with patients with isolated increase of PVR or DPG. Pulmonary vascular resistance has a better predictive value than DPG in patients with PH-LHD.