Baseline Pulmonary Vascular Resistance Research Articles

Macitentan for the treatment of portopulmonary hypertension (PORTICO): a multicentre, randomised, double-blind, placebo-controlled, phase 4 trial

No dedicated randomised clinical trials have evaluated therapies for pulmonary arterial hypertension in patients with portopulmonary hypertension. The endothelin receptor antagonist macitentan has demonstrated long-term efficacy in pulmonary arterial hypertension with a good hepatic safety profile. We aimed to evaluate efficacy and safety of macitentan in patients with portopulmonary hypertension. PORTICO was a phase 4 study done in 36 centres in seven countries, consisting of a 12-week double-blind period (randomly assigned 1:1 to macitentan 10 mg or placebo once daily) followed by a 12-week open-label period. Adults (≥18 years) with portopulmonary hypertension, a 6-minute walk distance of 50 m or more, and with pulmonary vascular resistance of 320 dyn·s·cm-5 or more without severe hepatic impairment (Child-Pugh class C or model for end-stage liver disease score ≥19) were eligible. The primary endpoint was pulmonary vascular resistance at week 12, expressed as ratio of baseline in the full analysis set. Safety was assessed throughout. This trial is registered at ClinicalTrials.gov, number NCT02382016. Between June 23, 2015, and July 28, 2017, 85 patients were randomly assigned to macitentan (n=43) or placebo (n=42). At baseline, 54 (64%) were receiving background therapy for pulmonary arterial hypertension. Most patients were WHO functional class II (50, 59%) or III (33, 39%) with a mean 6-minute walk distance of 384·5 m (SD 103·9). At week 12, the geometric mean ratio of baseline pulmonary vascular resistance was 0·63 (95% CI 0·58-0·67) in the macitentan group and 0·98 (95% CI 0·91-1·05) in the placebo group, corresponding to a ratio of geometric mean for pulmonary vascular resistance of 0·65 (95% CI 0·59-0·72, p<0·0001), which in turn represented a 35% (95% CI 28-41) reduction in pulmonary vascular resistance with macitentan versus placebo. During the double-blind period, 36 (84%) macitentan-treated and 33 (79%) placebo-treated patients had adverse events, and nine (21%) and six (14%), had serious adverse events. Four (9%) macitentan-treated patients had an adverse event leading to discontinuation versus none in the placebo group. The most frequent adverse event during the double-blind period was peripheral oedema (11 [26%] in the macitentan group and five [12%] in the placebo group). Macitentan significantly improved pulmonary vascular resistance in portopulmonary hypertension patients, with no hepatic safety concerns. Actelion Pharmaceuticals Ltd.

Loss of acid-sensing ion channel 2 enhances pulmonary vascular resistance and hypoxic pulmonary hypertension.

Acid-sensing ion channels (ASICs) are voltage-insensitive cation channels that contribute to cellular excitability. We previously reported that ASIC1 in pulmonary artery smooth muscle cells (PASMC) contribute to pulmonary vasoreactivity and vascular remodeling during the development of chronic hypoxia (CH)-induced pulmonary hypertension. However, the roles of ASIC2 and ASIC3 in regulation of pulmonary vasoreactivity and the development of CH-induced pulmonary hypertension are unknown. We tested the hypothesis that ASIC2 and ASIC3 contribute to increased pulmonary vasoreactivity and development of CH-induced pulmonary hypertension using ASIC2- and ASIC3-knockout (-/-) mice. In contrast to this hypothesis, we found that ASIC2-/- mice exhibit enhanced CH-induced pulmonary hypertension compared with WT and ASIC3-/- mice. This response was not associated with a change in ventilatory sensitivity or systemic cardiovascular function but was instead associated with direct changes in pulmonary vascular reactivity and pulmonary arterial morphology in ASIC2-/- mice. This increase in reactivity correlated with enhanced pulmonary arterial basal tone, elevated basal PASMC [Ca2+] and store-operated calcium entry (SOCE) in PASMC from ASIC2-/- mice. This increase in PASMC [Ca2+] and vasoreactivity was dependent on ASIC1-mediated Ca2+ influx but was not contingent upon an increase in ASIC1 mRNA or protein expression in PASMC from ASIC2-/- mice. Together, the results from this study demonstrate an important role for ASIC2 to regulate pulmonary vascular reactivity and for ASIC2 to modulate the development of CH-induced pulmonary hypertension. These data further suggest that loss of ASIC2 enhances the contribution of ASIC1 to overall pulmonary vascular reactivity.NEW & NOTEWORTHY This study demonstrates that loss of ASIC2 leads to increased baseline pulmonary vascular resistance, enhanced responses to a variety of vasoconstrictor stimuli, and greater development of hypoxic pulmonary hypertension. Furthermore, these results suggest that loss of ASIC2 enhances the contribution of ASIC1 to pulmonary vascular reactivity.

Prognostic Implications of Baseline Pulmonary Vascular Resistance Determined by Transthoracic Echocardiography Before Transcatheter Aortic Valve Replacement

Elevated pulmonary vascular resistance (PVR) determined using right heart catheterization portends an adverse prognosis following transcatheter aortic valve replacement (TAVR). The prognostic role of preprocedural PVR determined noninvasively using transthoracic echocardiography has not been studied in the TAVR setting. Baseline clinical and echocardiographic variables from a prospective TAVR registry were analyzed to determine preprocedural PVR and its impact on late outcomes (all-cause mortality, stroke, readmission for heart failure, new-onset atrial fibrillation). Echocardiographic PVR was estimated by the ratio of peak tricuspid regurgitation velocity to the time-velocity integral of the right ventricular outflow tract. Ninety-seven patients were included in the study, with complete 3-year follow-up data available for all survivors. Mean PVR was 2.1±0.) WU in the entire cohort and 2.7±0.9 WU among patients with pulmonary hypertension. In the entire cohort, 29 patients (29.9%) died during the study period. Three-year all-cause mortality and composite adverse event rates were higher with increased versus normal PVR (55.6% vs 24.1% [P=.008] and 66.7% vs 41.8% [P=.06], respectively). By multivariate analysis, PVR as either a continuous (hazard ratio, 1.75; 95% CI, 1.1-2.81; P=.02) or a categorical (≥2.5 vs>2.5 WU; hazard ratio, 2.49; 95% CI, 1.09-5.71; P=.03) variable was independently associated with all-cause mortality. Although systolic pulmonary artery pressure was associated with all-cause mortality on univariate analysis, this association was not statistically significant on multivariate analysis accounting for PVR. PVR estimated using transthoracic echocardiography is an independent predictor of mortality at long-term follow-up after TAVR. Systolic pulmonary artery pressure was associated with increased late mortality, although this relation was not significant after adjustment for baseline variables and PVR.

Right ventricular afterload predicts long-term transition from parenteral to oral treprostinil in pulmonary arterial hypertension.

Despite the increasing trends, reports on long-term follow-up are limited on transitioning from parenteral to oral treprostinil therapy in patients with pulmonary arterial hypertension (PAH). We investigated both the effectiveness of parenteral to oral treprostinil transition and the characteristics associated with transition failure over a duration of two years. The study included 37 Group I functional class I and II patients with PAH on combination therapy. Patients were excluded if cardiac index ≤2.2 L/min/m2, right atrial pressure ≥11 mmHg, or 6-min walk distance ≤250 m. Patients were categorized as successful (STransition) or unsuccessful (UTransition) transition based on clinical stability, or a parenteral comparator (CParenteral) if they remained on parenteral therapy (no transition). All patients underwent two right heart catheterizations, one at enrollment and a second post transition. Of 24 total transition patients, 46% were classified as UTransition. UTransition occurred on average 577 days post transition. Both UTransition and STransition had similar hemodynamics at diagnosis and treprostinil dose before and after transition. Before transition, the pulmonary vascular resistance (PVR) was significantly higher in the UTransition (6.7 ± 2 WU) vs. STransition group (3.5 ± 1.5 WU). At follow-up catheterization, the UTransition group demonstrated further increases in PVR, greater than the CParenteral group, without recovery despite “rescue” therapy in the UTransition group. A pre-transition PVR of 4.16 WU discriminated the UTransition from the STransition group. While a subset of PAH patients on combination therapy may be safely transitioned from parenteral to oral treprostinil, caution should be exercised in patients with elevated baseline PVR to avoid irreversible destabilization.

Enhanced NO-dependent pulmonary vasodilation limits increased vasoconstrictor sensitivity in neonatal chronic hypoxia.

Augmented vasoconstrictor reactivity is thought to play an important role in the development of chronic hypoxia (CH)-induced neonatal pulmonary hypertension. However, whether this response to CH results from pulmonary endothelial dysfunction and reduced nitric oxide (NO)-mediated vasodilation is not well understood. We hypothesized that neonatal CH enhances basal tone and pulmonary vasoconstrictor sensitivity by limiting NO-dependent pulmonary vasodilation. To test this hypothesis, we assessed the effects of the NO synthase (NOS) inhibitor Nω-nitro-l-arginine (l-NNA) on baseline pulmonary vascular resistance (PVR) and vasoconstrictor sensitivity to the thromboxane mimetic U-46619 in saline-perfused lungs (in situ) from 2-wk-old control and CH (12-day exposure, 0.5 atm) Sprague-Dawley rats. Basal tone was defined as that reversed by exogenous NO (spermine NONOate). CH neonates displayed elevated right ventricular systolic pressure (in vivo) and right ventricular hypertrophy, indicative of pulmonary hypertension. Perfused lungs from CH rats demonstrated greater baseline PVR, basal tone, and U-46619-mediated vasoconstriction compared with control rats in the absence of l-NNA. l-NNA markedly increased baseline PVR and reactivity to U-46619 in lungs from CH neonates, further augmenting vasoconstrictor sensitivity compared with control lungs. Exposure to CH also enhanced NO-dependent vasodilation to arginine vasopressin, pulmonary expression of NOS III [endothelial NOS (eNOS)], and eNOS phosphorylation at activation residue Ser1177 However, CH did not alter lung nitrotyrosine levels, a posttranslational modification reflecting [Formula: see text] scavenging of NO. We conclude that, in contrast to our hypothesis, enhanced basal tone and agonist-induced vasoconstriction after neonatal CH is limited by increased NO-dependent pulmonary vasodilation resulting from greater eNOS expression and phosphorylation at activation residue Ser1177NEW & NOTEWORTHY This research is the first to demonstrate enhanced nitric oxide-dependent vasodilation that limits increased vasoconstrictor reactivity in neonatal pulmonary hypertension. These results suggest that augmented vasoconstriction in this setting reflects changes in smooth muscle reactivity rather than a reduction in nitric oxide-dependent pulmonary vasodilation.

Pulmonary Arterial Compliance in Acute Respiratory Distress Syndrome: Clinical Determinants and Association With Outcome From the Fluid and Catheter Treatment Trial Cohort.

Pulmonary vascular dysfunction is associated with adverse prognosis in patients with the acute respiratory distress syndrome; however, the prognostic impact of pulmonary arterial compliance in acute respiratory distress syndrome is not established. We performed a retrospective analysis of 363 subjects with acute respiratory distress syndrome who had complete baseline right heart catheterization data from the Fluid and Catheter Treatment Trial to test whether pulmonary arterial compliance at baseline and over the course of treatment predicted mortality. Baseline pulmonary arterial compliance (hazard ratio, 1.18 per interquartile range of 1/pulmonary arterial compliance; 95% CI, 1.02-1.37; p = 0.03) and pulmonary vascular resistance (hazard ratio, 1.28 per interquartile range; 95% CI, 1.07-1.53; p = 0.006) both modestly predicted 60-day mortality. Baseline pulmonary arterial compliance remained predictive of mortality when pulmonary vascular resistance was in the normal range (p = 0.02). Between day 0 and day 3, pulmonary arterial compliance increased in acute respiratory distress syndrome survivors and remained unchanged in nonsurvivors, whereas pulmonary vascular resistance did not change in either group. The resistance-compliance product (resistance-compliance time) increased in survivors compared with nonsurvivors, suggesting improvements in right ventricular load. Baseline measures of pulmonary arterial compliance and pulmonary vascular resistance predict mortality in acute respiratory distress syndrome, and pulmonary arterial compliance remains predictive even when pulmonary vascular resistance is normal. Pulmonary arterial compliance and right ventricular load improve over time in acute respiratory distress syndrome survivors. Future studies should assess the impact of right ventricular protective acute respiratory distress syndrome treatment on right ventricular afterload and outcome.

The effects of pulmonary vasodilating agents on right ventricular parameters in severe group 3 pulmonary hypertension: a pilot study.

Pulmonary arterial hypertension (PAH)-approved vasodilators improve right ventricular (RV) function in patients with PAH. However, whether PAH-approved drugs ameliorate RV morphology and function in lung disease-associated pulmonary hypertension (lung-PH) remains unclear. We aimed to prospectively evaluate the changes in RV volume and ejection fraction (RVEF) in 14 consecutive severe lung-PH patients treated with PAH-approved vasodilators. Severe lung-PH was defined as a mean pulmonary arterial pressure (MPAP) of ≥35 mmHg or an MPAP of ≥25 mmHg with a cardiac index (L/min/m2) of <2. Right heart catheterization and cardiac magnetic resonance (CMR) imaging were performed at baseline and at 3 months after starting sildenafil with or without other PAH-approved drugs. Follow-up was conducted at 3 months in 11 participants; compared with baseline values, MPAP and pulmonary vascular resistance (PVR) decreased by 18% and 37%, respectively. Baseline CMR imaging revealed an elevated RV end-diastolic volume index (RVEDVI; mL/m2) of 117.5 ± 35.9 and a below-average RVEF of 25.2% ± 7.2%; after 3 months, RVEDVI decreased by 23.7% (P = 0.0061) and RVEF increased by 32.9% (P = 0.0165). Among the 11 patients, 3 were thought to be a stable and homogenous subset in terms of background lung disease and medical management administered. These 3 patients exhibited similar ameliorations in PVR and RVEF, compared with the other 8 patients. PAH-approved drug treatment may improve RV dilatation and systolic function among patients with severe lung-PH. This study was approved by University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) on September 1, 2013 (UMIN000011541).

Severity of Pulmonary Hypertension and Obesity are Not Associated with Worse Functional Outcomes after Pulmonary Thromboendarterectomy

Predictors of functional outcomes in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing pulmonary thromboendarterectomy (PTE) are important to identify preoperatively. We hypothesized that baseline severity of pulmonary hypertension and obesity would not be associated with 6-month functional outcomes after PTE. Clinical and hemodynamic data were collected on consecutive patients undergoing PTE from 2008 to 2014. Patients were stratified according to baseline pulmonary vascular resistance (PVR) and body mass index (BMI). Six-minute walk distance (6MWD), New York Heart Association functional class (FC), and echocardiography were assessed in each group at baseline and 6 months after PTE. Regression analyses were performed to evaluate for associations between functional outcomes and baseline PVR and BMI. Forty-two patients underwent PTE and had 6-month follow up data. In comparisons of patients with high and low baseline PVR, the baseline characteristics, distribution of disease, 6MWD, and FC were similar. Postoperative hemodynamics for both groups were similar. At 6 months, both groups achieved improvements in FC, and there were no between-group differences in the change in 6MWD or FC. In comparisons of obese and nonobese patients, perioperative and FC improvement were similar; however, obese patients achieved a greater improvement in 6MWD than nonobese patients (P = 0.04). In conclusion, our data suggest that baseline severity of CTEPH and obesity were not associated with worse functional outcome. Further studies are needed to confirm these results, as these findings could have implications for patient selection for PTE.

Pulmonary Hypertension After Heart Transplantation in Patients Bridged with the Total Artificial Heart.

Pulmonary hypertension (PH) among heart transplant recipients is associated with an increased risk of mortality. Pulmonary hemodynamics improves after left ventricular assist device (LVAD) implantation; however, the impact of PH before total artificial heart (TAH) implantation on posttransplant hemodynamics and survival is unknown. This is a single center retrospective study aimed to evaluate the impact of TAH implantation on posttransplant hemodynamics and mortality in two groups stratified according to severity of PH: high (≥3 Woods units [WU]) and low (<3 WU) baseline pulmonary vascular resistance (PVR). Hemodynamic data were obtained from right heart catheterization performed at baseline (before TAH) and posttransplant at 1 and 12 months. Patients in the high PVR group (n = 12) experienced improvement in PVR (baseline = 4.31 ± 0.7; 1-month = 1.69 ± 0.7, p < 0.001; 12-month = 48 ± 0.9, p < 0.001) and transpulmonary gradient (baseline = 15.8 ± 3.3; 1-month = 11.57 ± 5.0, p = 0.07; 12-month = 8.50 ± 4.0, p = 0.008) after transplantation, reaching similar values as the low PVR group at 12 months. The filling pressures improved in the high PVR group after heart transplantation (HT), but remained elevated. There was no significant difference in survival between the two groups at 12 months follow-up. Patients with high PVR who are bridged to transplant with TAH had improvement in PVR at 12 months after transplant, and the degree of PVR did not impact posttransplant survival.

Sodium Nitroprusside in Patients With Mixed Pulmonary Hypertension and Left Heart Disease: Hemodynamic Predictors of Response and Prognostic Implications

BackgroundMixed pulmonary hypertension (PH) in heart failure (HF) is defined by transpulmonary gradient ≥ 12 and/or pulmonary vascular resistance (PVR) ≥ 240 dyne/s/cm−5, but diastolic pressure gradient (DPG) ≥ 7 mmHg has been proposed more recently. We evaluated the acute hemodynamic response to sodium nitroprusside (SNP) specifically in relation to the proposed DPG criterion ≥7 mmHg and the prognostic significance of response to SNP in patients with mixed PH and advanced HF. MethodsNinety-eight consecutive patients with advanced HF and mixed PH underwent cardiac catheterization and acute SNP infusion. Baseline hemodynamic parameters included transpulmonary gradient, PVR, DPG, and pulmonary capacitance (PCap). Hemodynamic response to SNP was defined as a reduction in PVR of at least 20%. The composite endpoint was death/heart transplantation/mechanical circulatory support. ResultsSixty of the 98 patients were SNP responders. SNP resulted in significant reductions in filling pressures and PVR and increase in stroke volume and PCap. DPG (not baseline PVR) was significantly associated with hemodynamic response to SNP on logistic regression analysis. The sensitivity and specificity of a DPG ≥7 mmHg to identify nonresponders to SNP were 74% and 97%, respectively. At median follow-up of 218 (148–324) days, 13 and 19 patients of the SNP responders and nonresponders, respectively, met the composite endpoint (P = .021 by log-rank test). Hemodynamic response to SNP and PCap were independently associated with the composite outcome of survival free from transplantation/mechanical circulatory support. ConclusionBaseline DPG ≥ 7 mmHg is associated with poor PVR response to SNP. PVR response to SNP and PCap are associated with a more favorable prognosis in patients with advanced HF and mixed PH.

Differential Effects of Chronic Hypoxia on Basal and Agonist‐Induced NO‐Dependent Pulmonary Vasodilation in Neonatal Rats

Endothelial dysfunction contributes to chronic hypoxia (CH)‐induced pulmonary hypertension (PH) in neonates. However, whether basal and stimulated endothelium‐derived nitric oxide (EDNO)‐dependent pulmonary vasodilation are similarly impaired in neonatal PH is unclear. We hypothesized that CH attenuates EDNO‐dependent pulmonary vasodilation both basally and in response to receptor activation in a neonatal rat model of PH. To test this hypothesis, we assessed effects of the NO synthase inhibitor Nω‐nitro‐L‐arginine (L‐NNA; 300 μM) on baseline pulmonary vascular resistance (PVR) in salt‐perfused lungs (in situ) from 2‐wk‐old control and CH (2 wk at 0.5 atm) rats. The contribution of active tone to PVR was assessed by examining responses to exogenous NO (spermine NONOate, 100 μM). Lungs from CH rats showed greater baseline PVR compared to controls (p&lt;0.05) in the absence of L‐NNA. This response to CH reflected active tone, whereas no basal tone was observed in control lungs. Consistent with our hypothesis, L‐NNA modestly increased PVR in the control group (p&lt;0.05 vs. vehicle), but had no effect in lungs from CH neonates. We next examined EDNO‐dependent vasodilatory responses to arginine vasopressin (AVP, 25 nM) in U‐46619‐constricted lungs. Surprisingly, lungs from CH rats showed augmented responses to AVP compared to controls (p&lt;0.05). L‐NNA abolished AVP responses in both groups (p&lt;0.05 vs vehicle). We conclude that CH 1) increases basal PVR in part through vasoconstriction, and 2) impairs EDNO‐dependent pulmonary vasodilation under basal conditions, but paradoxically augments AVP‐induced EDNO‐dependent vasodilation in a neonatal rat model of PH.

The Impact of Targeted Therapies for Pulmonary Hypertension on Pediatric Intraoperative Morbidity or Mortality

Pulmonary hypertension (PHT) is a significant risk factor for major adverse events during anesthesia, with a reported incidence of 5% to 7%, secondary to acute pulmonary hypertensive crises or right ventricular ischemia. Newer therapies for treating PHT have reduced mortality. In this single-center study, we investigated the frequency of major and minor events during anesthesia under the current strategies to manage PHT. We reviewed the records of children with PHT who underwent noncardiopulmonary bypass procedures from 2008 to 2012. Clinically important symptoms, physical signs, and results of investigations present before anesthesia were recorded. The incidence and type of intraoperative complications and death (up to 7 days) were collected. Data were collected for 122 patients undergoing 284 procedures. Minor (3.9%) and major (3.2%) complication rates were unchanged from previous publications. The etiology of PHT was not significant for complications (P = 0.14). Disease-modifying agents were not associated with reduced complications: 4.1% in treated versus 8.6% untreated (all P > 0.14). Patients receiving home oxygen had more complications (P = 0.02). Multiple logistic regression identified age and degree of PHT as significant predictors of complications (all P ≤ 0.03). The risk for adverse events during anesthesia in patients with PHT remains high, despite newer disease-modifying treatments. Risk factors for complications include age and severity of PHT.

Riociguat for HF with Pulmonary Hypertension (PH): Post-hoc Analysis of LEPHT by Baseline Pulmonary Vascular Resistance (PVR) and Pulmonary Vascular Gradient (PVG)

Riociguat for HF with Pulmonary Hypertension (PH): Post-hoc Analysis of LEPHT by Baseline Pulmonary Vascular Resistance (PVR) and Pulmonary Vascular Gradient (PVG)

Bosentan in pulmonary hypertension associated with fibrotic idiopathic interstitial pneumonia.

Pulmonary hypertension (PH) associated with fibrotic idiopathic interstitial pneumonia (IIP; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia) confers important additional morbidity and mortality. To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group. In a randomized, double-blind, placebo-controlled study, 60 patients with fibrotic IIP and right heart catheter confirmed PH were randomized 2:1 to bosentan (n = 40) or placebo (n = 20). The primary study endpoint was a fall from baseline pulmonary vascular resistance index (PVRi) of 20% or more over 16 weeks. Sixty patients (42 men; mean age, 66.6 ± 9.2 yr), with a mean pulmonary artery pressure of 36.0 (± 8.9) mm Hg, PVRi 13.0 (± 6.7) Wood Units/m(2) and reduced cardiac index of 2.21 (± 0.5) L/min/m(2) were recruited to the study. Accounting for deaths and withdrawals, paired right heart catheter data were available for analysis in 39 patients (bosentan = 25, placebo = 14). No difference in the primary outcome was detected, with seven (28.0%) patients receiving bosentan, and four (28.6%) receiving placebo achieving a reduction in PVRi of greater than or equal to 20% (P = 0.97) at 16 weeks. There was no change in functional capacity or symptoms between the two groups at 16 weeks, nor any difference in rates of serious adverse events or deaths (three deaths in each group). This study shows no difference in invasive pulmonary hemodynamics, functional capacity, or symptoms between the bosentan and placebo groups over 16 weeks. Our data do not support the use of the dual endothelin-1 receptor antagonist, bosentan, in patients with PH and fibrotic IIP. Clinical trial registered with www.clinicaltrials.gov (NCT 00637065).

Effect of high altitude exposure on the hemodynamics of the bidirectional Glenn physiology: Modeling incremented pulmonary vascular resistance and heart rate

The considerable blood mixing in the bidirectional Glenn (BDG) physiology further limits the capacity of the single working ventricle to pump enough oxygenated blood to the circulatory system. This condition is exacerbated under severe conditions such as physical activity or high altitude. In this study, the effect of high altitude exposure on hemodynamics and ventricular function of the BDG physiology is investigated. For this purpose, a mathematical approach based on a lumped parameter model was developed to model the BDG circulation. Catheterization data from 39 BDG patients at stabilized oxygen conditions was used to determine baseline flows and pressures for the model. The effect of high altitude exposure was modeled by increasing the pulmonary vascular resistance (PVR) and heart rate (HR) in increments up to 80% and 40%, respectively. The resulting differences in vascular flows, pressures and ventricular function parameters were analyzed. By simultaneously increasing PVR and HR, significant changes (p <0.05) were observed in cardiac index (11% increase at an 80% PVR and 40% HR increase) and pulmonary flow (26% decrease at an 80% PVR and 40% HR increase). Significant increase in mean systemic pressure (9%) was observed at 80% PVR (40% HR) increase. The results show that the poor ventricular function fails to overcome the increased preload and implied low oxygenation in BDG patients at higher altitudes, especially for those with high baseline PVRs. The presented mathematical model provides a framework to estimate the hemodynamic performance of BDG patients at different PVR increments.

RETRACTED: Right to left ventricular volume ratio: A novel marker of disease severity in chronic thromboembolic pulmonary hypertension

[This retracts the article DOI: 10.1016/j.ijchv.2013.10.001.].

Do preoperative haemodynamic data and reactivity test predict the postoperative reversibility of pulmonary arterial hypertension in patients with large ventricular septal defect and borderline operability?

BackgroundDecisions to operate on patients with shunt lesions presenting late with severe pulmonary arterial hypertension (PAH) and borderline operability are often not based on precise cut off values of haemodynamic...

Pulmonary Edema Predictive Scoring Index (PEPSI), a New Index to Predict Risk of Reperfusion Pulmonary Edema and Improvement of Hemodynamics in Percutaneous Transluminal Pulmonary Angioplasty

This study sought to identify useful predictors for hemodynamic improvement and risk of reperfusion pulmonary edema (RPE), a major complication of this procedure. Percutaneous transluminal pulmonary angioplasty (PTPA) has been reported to be effective for the treatment of chronic thromboembolic pulmonary hypertension (CTEPH). PTPA has not been widespread because RPE has not been well predicted. We included 140 consecutive procedures in 54 patients with CTEPH. The flow appearance of the target vessels was graded into 4 groups (Pulmonary Flow Grade), and we proposed PEPSI (Pulmonary Edema Predictive Scoring Index) = (sum total change of Pulmonary Flow Grade scores) × (baseline pulmonary vascular resistance). Correlations between occurrence of RPE and 11 variables, including hemodynamic parameters, number of target vessels, and PEPSI, were analyzed. Hemodynamic parameters significantly improved after median observation period of 6.4 months, and the sum total changes in Pulmonary Flow Grade scores were significantly correlated with the improvement in hemodynamics. Multivariate analysis revealed that PEPSI was the strongest factor correlated with the occurrence of RPE (p < 0.0001). Receiver-operating characteristic curve analysis demonstrated PEPSI to be a useful marker of the risk of RPE (cutoff value 35.4, negative predictive value 92.3%). Pulmonary Flow Grade score is useful in determining therapeutic efficacy, and PEPSI is highly supportive to reduce the risk of RPE after PTPA. Using these 2 indexes, PTPA could become a safe and common therapeutic strategy for CTEPH.

THU0248 Efficacy of imatinib mesylate on scleroderma associated pulmonary arterial hypertension

BackgroundScleroderma is an autoimmune disorder mainly characterized by progressive dermal and vascular fibrosis. It has been reported that abnormal signaling through the platelet derived growth factor (PDGF) and transforming growth...

Current era survival of patients with pulmonary arterial hypertension associated with congenital heart disease: a comparison between clinical subgroups

This study compared the clinical, functional, and haemodynamic characteristics and current era survival of subgroups of patients with pulmonary arterial hypertension associated with congenital heart disease (PAH-CHD): Eisenmenger syndrome (ES); PAH-CHD associated with systemic-to-pulmonary shunts (SPs); PAH with small defects (SDs); and PAH after defect correction (CDs). Data from consecutive PAH-CHD patients referred to our centre from 1 January 1998 to 31 May 2011 were collected. A contemporary group of idiopathic PAH patients was utilized for comparison. Treatment was per PAH guidelines, including combination therapy, with approved PAH-specific drugs. Survival was assessed with Kaplan-Meier analysis from the first invasive haemodynamic confirmation of PAH and compared across subgroups by log-rank test. Of 192 patients (mean age 41 ± 17 years; 61% female), 90 had ES (aged 41 ± 16 years); 48 SP (aged 47 ± 18 years); 10 SD (aged 25 ± 21 years); and 44 CD (aged 36 ± 17 years). Patients with ES had the highest baseline pulmonary vascular resistance and the lowest exercise capacity. Seventy-eight per cent were treated with approved PAH-specific drugs, and 44% were treated with combination therapy. Kaplan-Meier survival estimates (95% confidence interval) at 20 years for ES, SP, and CD were 87% (77-93%), 86% (60-96%), and 36% (12-72%, P = 0.0001 vs. ES; P = 0.004 vs. SP), respectively, and at 15 years for SD was 66% (16-91%, P = 0.015 vs. ES; P = 0.016 vs. SP). The survival of the 278 patients with idiopathic PAH appeared to be worse when compared with the PAH-CHD subgroups. Relevant clinical, functional, haemodynamic, and survival differences were observed among subgroups. In particular, patients with CD and SD had the worst survival. These findings should be considered when planning medical or interventional treatment strategies in PAH-CHD patients.