Non-operable Chronic Thromboembolic Pulmonary Hypertension Research Articles

[Hemodynamic changes with serial balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension].

Objective: To monitor hemodynamic changes during serial balloon pulmonary angioplasty (BPA) for chronic thromboembolic pulmonary hypertension (CTEPH). Methods: General clinical data of CTEPH patients diagnosed from October 2017 to January 2022 in Beijing Chaoyang Hospital were collected, and 83 patients who underwent at least 1 BPA treatment were included to analyze their 6 min walking distance, WHO functional class, N-terminal B-type natriuretic peptide precursor (NT-proBNP), troponin I (cTnI) and haemodynamic indices. Baseline and follow-up after the final BPA clinical data and hemodynamics, functional status and serial hemodynamics before each series of BPA were collected to evaluate the efficacy of BPA for CTEPH patients. Complications and managements were documented to confirm the safety of BPA for CTEPH patients. Results: Three hundred and forty BPA procedures were performed in 83 CTEPH patients. The median number of BPA procedures was 4.0 and a total of 2104 vessels were dilated. In general, mPAP [from 50.0(42.0-55.25) mmHg(1 mmHg=0.133 kPa) to 32.0(27.0-42.0) mmHg, P<0.001], PVR[from (806.6±323.2) dyn·s·cm-5 to 420.0(295.0-613.5) dyn·s·cm-5, P<0.001] were significantly improved compared with baseline, but not CO and CI. Functional parameters including WHO functional class Ⅰ/Ⅱ/Ⅲ/Ⅳ (from 0/35/34/14 to 43/32/7/1, P<0.001), 6MWD [from 364.5(300.0-429.5)m to 461.0(409.0-501.0)m, P<0.001], NT-proBNP [from 1 357.0(232.0-2 715.0) ng/L to 141.0(57.0-627.8) ng/L,P<0.001] were significantly improved compared with baseline. A cumulative (compared to baseline) and serial (compared to preceding BPA session) analysis of the sequential BPA session confirmed that a major hemodynamic improvement in PVR and mPAP occurred in the first 3 serial BPA treatments. There was a dose-response relationship: the more segments that were treated, the greater were the subsequent reduction in PVR and mPAP. There were 32.0 complications (9.4%) associated with BPA procedures, and the most common complication was pulmonary hemorrhage caused by catheter-related vascular injury. Conclusions: BPA is an effective and safe alternative for technically non-operable CTEPH patients. The hemodynamic benefits of BPA in CTEPH patients were cumulative and correlated with the total number of vessels successfully dilated.

Safety of inhaled nitric oxide withdrawal in severe chronic pulmonary hypertension.

Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator with a safety concern due to rebound pulmonary hypertension (PH) associated with its withdrawal. We report short-term pulsed iNO in patients with severe pulmonary arterial hypertension (PAH) and nonoperable chronic thromboembolic PH (nCTEPH). This is a retrospective analysis of 33 patients: 22 with PAH and 11 with nCTEPH. We assessed hemodynamic, echocardiographic, and other noninvasive variables to evaluate safety and efficacy of iNO. We performed an iNO withdrawal test during right heart catheterization and after 3 days of iNO treatment. iNO significantly improved all variables examined in 22 patients with PAH and 11 with nCTEPH. Two patterns of response were observed after sudden iNO withdrawal. Twenty-nine patients (88%) showed minimal hemodynamic, oxygenation and clinical changes. Four patients (12%) had a reduction in cardiac index ≥20% and PaO2 ≥ 5%, three patients did not show clinical deterioration, and one patient developed hemodynamic collapse that needed iNO administration. This retrospective study suggests that short-term iNO improves hemodynamics and clinical conditions in some patients with PAH an nCTPEH. However, pulsed iNO withdrawal PH rebound could be a serious concern in these patients. Given the lack of evidence, we do not recommend the use of pulsed iNO in the treatment of patients with chronic PH.

Efficacy and Safety of Balloon Pulmonary Angioplasty for Patients With Chronic Thromboembolic Pulmonary Hypertension and Comorbid Chronic Obstructive Pulmonary Disease.

Background Balloon pulmonary angioplasty (BPA) is a promising treatment modality for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for atypical CTEPH with concurrent chronic obstructive pulmonary disease (COPD) remains controversial owing to the risk of exacerbation of ventilation-perfusion mismatch. We aimed to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Methods and Results Data from 149 patients with CTEPH, who underwent BPA from March 2011 to June 2021, were retrospectively analyzed. Patients were divided based on COPD comorbidity: the COPD group (n=32, defined as forced expiratory volume in 1 second/forced vital capacity <70% and forced expiratory volume in 1 second <80% predicted) and the non-COPD group (n=101); patients with mild COPD (n=16) were excluded. Hemodynamic and respiratory parameters were compared between the groups. Hemodynamics improved similarly in both groups (reduction in pulmonary vascular resistance): -55.6±29.0% (COPD group) and -58.9±21.4% (non-COPD group); P=nonsignificant. Respiratory function and oxygenation improved in the COPD group (forced expiratory volume in 1 second/forced vital capacity [61.8±7.0% to 66.5±10.2%, P=0.02] and arterial oxygen partial pressure [60.9±10.6 mm Hg to 69.3±13.6 mm Hg, P<0.01]). Higher vital capacity (P=0.024) and higher diffusing capacity for lung carbon monoxide (P=0.028) at baseline were associated with greater improvement in oxygenation in the multivariable linear analysis. Lung injury per BPA session was 1.6% in the COPD group. Conclusions The efficacy and safety of BPA for nonoperable CTEPH in patients with comorbid COPD were similar to those in patients without COPD. Oxygenation and forced expiratory volume in 1 second/forced vital capacity improved in patients with COPD. BPA should be considered in patients with CTEPH with concurrent COPD.

Balloon pulmonary angioplasty: are we there yet? Lessons learned and unanswered questions.

Evidence supporting the use of balloon pulmonary angioplasty #BPA, which has drastically changed management of non-operable chronic thromboembolic pulmonary hypertension #CTEPH, and rationale for a future multimodal approach with combined medical therapy https://bit.ly/3F7ccKD.

Efficacy and safety of balloon pulmonary angioplasty for patients with chronic thromboembolic pulmonary hypertension comorbid to chronic obstructive pulmonary disease

Abstract Background Balloon pulmonary angioplasty (BPA) would be promising treatment option for non-operable chronic thromboembolic pulmonary hypertension (CTEPH). However, BPA for CTEPH with Chronic obstructive pulmonary disease (COPD) might exacerbate ventilation perfusion mismatch. The aim is to evaluate the efficacy and safety of BPA for CTEPH with moderate or severe COPD. Method Data from 149 CTEPH patients were collected retrospectively who underwent BPA from March 2011 to June 2021. Patients were divided according to the comorbidity of COPD: a COPD group (defined as forced expiratory volume in one second (FEV1.0) / forced vital capacity (FVC)&amp;lt;70% and FEV1.0&amp;lt;80% predicted [n=32]) or a non-COPD group [n=101]. Mild COPD patients (n=16) were excluded. Hemodynamics and respiratory parameters were compared. Results Hemodynamics improved similarly in both group (percent decrease of pulmonary vascular resistance; −61.1±12.3% in a COPD group, −65.8±11.1% in a non-COPD group, p=N.S). Patients in a COPD group showed improved respiratory function and oxygenation with FEV1.0% from 61.8±7.0% to 66.5±10.2% (p=0.02), and partial pressure of arterial oxygen from 60.9±10.6mmHg to 69.3±13.6mmHg (p&amp;lt;0.01). Higher vital capacity (r2=0.123, p=0.024), higher diffusing capacity for lung carbon monoxide (r2=0.308, p=0.028) at baseline were correlated with larger improvement of oxygenation after BPA in multivariate linear analyses. Lung injury per session was 1.6% in a COPD group. Conclusion The efficacy and safety of BPA for non-operable CTEPH with COPD were equivalent to those of patients without COPD. Oxygenation and FEV1.0% also improved in COPD patients. BPA might be considered even though patients comorbid COPD. Funding Acknowledgement Type of funding sources: None.

The results of the balloon pulmonary angioplasty program in chronic thromboembolic pulmonary hypertension patients in a national and European reference center resemble those of Japanese series

Abstract Introduction Balloon pulmonary angioplasty (BPA) is an established technique in patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH). It improves hemodynamics, functional class, biomarkers and survival, with current periprocedural mortality rates below 1–2% in experienced centers. However, there is a discrepancy between the magnitude of European or American series' results and those of Japanese centers, with a pulmonary vascular resistance reduction of 26–43% in the former and 45–65% in the latter. Purpose To present the results of the BPA program of a CTEPH national and European reference center and to compare them with the results of Japanese series. Methods We analyze the improvement in hemodynamics, functional parameters, biomarkers and pulmonary vasodilators requirements of patients with a finished BPA program. Besides, we show safety and survival of the whole cohort of patients undergoing BPA between May 2013 and December 2020 in a CTEPH national and European reference center. Results We performed 503 BPA sessions in 120 patients, 64% women, mean age 61±15 years (19–84). The reasons for BPA were: distal involvement in 105 patients, comorbidities in 3 patients, personal preferences in 3 patients and residual pulmonary hypertension after pulmonary thromboendarterectomy in 9 patients. Mean follow-up from therapy beginning was 50±16 months (22–92). One patient died 7 days after her first BPA due to severe lung injury (peri-procedural mortality 0.83%). BPA therapy was interrupted in 5 patients (4 octogenarians with poor tolerance to procedures or little clinical improvement and 1 patient with relapsing severe hemoptysis during BPA sessions). Seventy three of the 114 remaining patients had finished their BPA program. The table shows the hemodynamic, biomarker and functional class improvement and the decrease in pulmonary vasodilators requirements of patients with complete BPA therapy. During follow-up 2 patients died: one due to hemoptysis related to pneumonia, 23 months after his first BPA, with BPA program already completed; the other due to leukemia, while in active BPA program. Thus, survival of our BPA series at 7 years follow-up is 98.2%. Conclusions The efficacy, safety and survival results of BPA therapy in patients with inoperable CTEPH at a national and European reference CTEPH center are comparable to those of Japanese series. Furthermore, hemodynamic and functional improvement and the reduction of specific medication requirements, along with therapy safety, position BPA as the first choice therapeutic option in patients not subsidiary of surgery. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): University Hospital 12 de Octubre, Madrid, Spain Changes after complete BPA therapySurvival from the initial BPA procedure

Survival in patients with chronic thromboembolic pulmonary hypertension in the modern management era

Abstract Background The management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has recently evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched BPA program since 2011. The aim was to analyze survival and treatment efficacy in the modern management era. Method and result We retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed in our university from January 2011 (i.e. after the availability of BPA) to December 2019. Forty-one patients underwent PEA, in these 25 patients underwent additional BPA (Hybrid group) and other patients were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group), remaining 12 patients had not undergone any interventional treatments. The 1- and 5-year survival rates of operated patients (n=41) were 97.4% and 90.0%, compared to96.9% and 86.9% in not-operated patients (n=102), respectively (p=0.579) (Figure). There was no death in Hybrid group. Percent decrease of pulmonary vascular resistance in PEA group, Hybrid group, BPA group were −75.4±9.9%, −74.3±11.8%, −56.3±22.2%, respectively (p&amp;lt;0.01, one-way ANOVA). Absolute decrease of mean pulmonary artery pressure in each groups were −20.3±9.5mmHg, −24.5±8.8mmHg, −16.4±9.2mmHg, respectively (p&amp;lt;0.01, one-way ANOVA). Conclusion There was no longer significant difference of long-term survival between operated and not-operated CTEPH. Moreover, Hybrid approach might have the potential to lead notable improvement in the prognosis of CTEPH. BPA and PEA would be mutually complementary therapies in the modern management era. Figure 1 Funding Acknowledgement Type of funding source: None

Systematic Review: Does Balloon Pulmonary Angioplasty (BPA) Improve Right Ventricular Function in CTEPH Patients? Evaluation Based on Imaging Findings

Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening disease with many complications, such as right heart failure. Therefore, a direct and efficient therapy is imperative. This review aims to determine the effectiveness of balloon pulmonary angioplasty (BPA) on right ventricular (RV) function among CTEPH patients, using imaging methods. From April 2019 to August 2019, PubMed database was searched for randomized control trials and cohort studies conducted until August 2019, evaluating the impact of BPA on RV function as assessed by non-invasive modalities. Data were extracted, and validity was assessed by 2 reviewers and graded using the Cochrane Collaboration tool for assessing a risk of bias. A total of 204 articles were screened for relevance. Only 14 articles were deemed eligible for this review, 4 studies being prospective and 10 retrospective trials. Totally 395 patients with CTEPH who underwent BPA enrolled. The findings indicated improvement in hemodynamic parameters and RV function. BPA is an effective and appropriate therapy for non-operable CTEPH patients leading to significant improvements in RV function. Two-dimensional and 3D echocardiography and cardiac magnetic resonance imaging (CMRI) are reliable non-invasive imaging methods for RV function assessment after BPA.

The role of balloon pulmonary angioplasty and pulmonary endarterectomy: Is chronic thromboembolic pulmonary hypertension still a life-threatening disease?

BackgroundThe management of non-operable chronic thromboembolic pulmonary hypertension (CTEPH) has evolved with the availability of balloon pulmonary angioplasty (BPA) and pulmonary vasodilators. We launched the BPA program in 2011. The aim was to analyze the survival and treatment efficacy of our CTEPH treatment program in the modern management era. Methods and resultsWe retrospectively reviewed data from 143 consecutive CTEPH patients diagnosed from January 2011 (i.e. after the availability of BPA) to December 2019. Of forty-one patients who underwent pulmonary endarterectomy (PEA), 25 underwent additional BPA (Combination group) and the others were treated with only PEA (PEA group). Ninety patients underwent BPA (BPA group). The remaining 12 patients did not undergo any interventional treatments.The 1- and 5-year survival rates of operated patients (n = 41) were 97.4% and 90.0%, compared to 96.9% and 86.9% in not-operated patients (n = 102), respectively (p = 0.579). There was no mortality in the Combination group. Mean pulmonary artery pressure after treatments in the PEA only, Combination, and BPA only groups was 20.5 ± 6.7, 17.9 ± 4.9, and 20.7 ± 4.6 mmHg, respectively (p = 0.067, one-way ANOVA). Percent decrease of pulmonary vascular resistance in each treatment groups was −73.7 ± 11.3%, −74.3 ± 11.8%, and − 54.9 ± 22.5%, respectively (p < 0.01, one-way ANOVA). ConclusionThere was no significant difference in long-term survival between operated and not-operated CTEPH. Moreover, the Combination approach might have the potential to introduce notable improvements in the prognosis of CTEPH. BPA and PEA appear to be mutually complementary therapies in the modern management era.

The Evolving Role of Balloon Pulmonary Angioplasty in the Management of Chronic Thromboembolic Pulmonary Hypertension

Patients with chronic thromboembolic pulmonary hypertension (CTEPH), characterized by pulmonary artery obstruction with unresolved embolism, have poor prognosis. Although pulmonary endarterectomy is the treatment of choice in the management of CTEPH, some patients are not operable. Balloon pulmonary angioplasty (BPA) is a catheter-based interventional treatment for patients with CTEPH. BPA has been considered a high-risk procedure, although the beneficial effects were promising. BPA has been modified and refined over the last 10 years. Recent evidence about modern BPA has consistently demonstrated the beneficial clinical effects with acceptable risks. BPA is now recommended in nonoperable CTEPH patients in addition to targeted medical therapy, although several questions such as long-term prognosis remain unanswered. BPA is still evolving for its application in the CTEPH treatment strategy. Further investigations are still necessary to define the role of BPA.

P5022Dual-energy CT was effective to evaluate of microvasculopathy in chronic thromboembolic pulmonary hypertension

Abstract Background The existence of microvasculopathy in patients with chronic thromboembolic pulmonary hypertension (CTEPH) had been suggested. However, the impact of microvasculopathy for pathophysiology had been unknown. Recently dual-energy CT (DECT) can produce a sensitive iodine distribution map as blood perfusion in lung fields to quantify lung perfusion, also can suggest the existence of microvasculopathy according to poor subpleural perfusion which was published previously. Methods We retrospectively reviewed poor subpleural perfusion (defined as subpleural spaces either not or minimally perfused in all segments) and hemodynamics of 83 treatment-naïve CTEPH patients who underwent DECT from February 2014 to Jan 2019. Patients were divided according to poor subpleural perfusion: a microvasculopathy group (n=44) or a non-microvasculopathy group (n=39). We assessed cardiopulmonary exercise test, right heart catheterization and DECT parameters as quantitative evaluation of pulmonary blood volume (PBV). PBV was calculated as the average of entire lung iodine density. Results PBV value in non-microvasculopathy group showed significant inverse correlation with pulmonary vascular resistance (PVR) (y = 14236 x-1.028 r=−0.530, p&lt;0.01). PBV, SvO2, and %DLCO/VA were significantly lower (22.0 vs. 26.4, p&lt;0.01, 61.3 vs. 66.0, p&lt;0.01, and 59.2 vs 75.9 p&lt;0.01), and systolic pulmonary arterial pressure, PVR, VE/VCO2 slope, BNP were higher (69.3 vs 60.6 p=0.04, 834 vs 586 p&lt;0.01, 45.5 vs. 37.8, p=0.02, and 440 vs 122 p=0.04) in microvasculopathy group, while the other parameters were similar between the two groups. Multivariate analysis revealed that %DLCO/VA was the only predictor of microvasculopathy (OR,0.895 [95% CI, 0.835 - 0.960]; P&lt;0.01). Conclusion Pulmonary blood flow of patients in non-micorvasculopathy group showed inverse correlation with PVR. DECT was effective to assess the microvasculopathy in CTEPH. In our experience, less than 60% of non-operable CTEPH patients have microvasculopathy.

Balloon Pulmonary Angioplasty for the Treatment of Nonoperable Chronic Thromboembolic Pulmonary Hypertension: Single-Center Experience with Low Initial Complication Rate

PurposeTo evaluate the safety and efficacy of balloon pulmonary angioplasty (BPA) for nonoperable chronic thromboembolic pulmonary hypertension (CTEPH) patients during the initial experience of a single center. MethodsA total of 18 CTEPH patients (5 with residual pulmonary hypertension after pulmonary endarterectomy) were treated with BPA during the period 2014–2018 and were retrospectively reviewed. Mean age was 61 ± 19 years; 55% were female; mean pulmonary artery pressure was 44 ± 12 mmHg; cardiac output was 4.3 ± 1.0 l/min; and pulmonary vascular resistance was 8.4 ± 3.6 WU. Patients were evaluated by New York Heart Association functional class, 6-minute walk distance, N-terminal pro b-type natriuretic peptide, echocardiography, right heart catheterization, and before and after completions of BPA. ResultsA total of 91 procedures were performed, with a median number of 4 BPA sessions per patient (range, 2–8). There were no deaths or major complications requiring extracorporeal support or (non)invasive ventilation. The most common complication was self-limiting hemoptysis (3%). According to Society of Interventional Radiology classification, 4 mild, 4 moderate, and 1 severe adverse events were noted. Invasive hemodynamics significantly improved, with a cardiac index increase of 15% (P = .0333), decrease of mean pulmonary artery pressure of 30% (P = .0013), and decrease of pulmonary vascular resistance of 45% (P = .0048). Stroke volume index (P = .0171) and pulmonary arterial compliance (P = .0004) were also significantly enhanced. ConclusionsBPA significantly improves cardiopulmonary hemodynamics with an acceptable safety profile. Further studies assessing the long-term efficacy of BPA are required.

Subcutaneous treprostinil for the treatment of severe non-operable chronic thromboembolic pulmonary hypertension (CTREPH): a double-blind, phase 3, randomised controlled trial

Treprostinil, a prostacyclin analogue, is effective for the treatment of pulmonary arterial hypertension. However, information is scarce regarding treprostinil for treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The aim of this study was to examine the efficacy and safety of subcutaneous treprostinil in this setting. In this 24-week, randomised, double-blind controlled trial, we enrolled patients with CTEPH, classified as non-operable, or with persistent or recurrent pulmonary hypertension after pulmonary endarterectomy, in six European expert centres in Austria, Czech Republic, Germany, and Poland. Patients in WHO functional class III or IV with a 6-min walk distance of 150-400 m were randomly assigned at a 1:1 allocation ratio to continuous high-dose subcutaneous treprostinil (target dose around 30 ng/kg per min at week 12) or low-dose subcutaneous treprostinil (target dose around 3 ng/kg per min at week 12). The primary endpoint was the change from baseline in 6-min walk distance at week 24. All patients who received at least one dose of the study drug were included in the intention-to-treat efficacy and safety analyses based on assessment of adverse events. The trial was registered at ClinicalTrialsRegister.eu EudraCT number 2008-006441-10 and ClinicalTrials.gov, number NCT01416636. From March 9, 2009, to June 9, 2016, 105 patients were enrolled with 53 (50%) patients randomly assigned to high-dose and 52 (50%) patients to low-dose subcutaneous treprostinil. At week 24, marginal mean 6-min walk distance improved by 44·98 m (95% CI 27·52 to 62·45) in the high-dose group, and by 4·29 m (95% CI -13·34 to 21·92) in the low-dose group (treatment effect 40·69 m, 95% CI 15·86 to 65·53, p=0·0016). 12 serious adverse events were reported in ten (19%) of 52 patients from the low-dose group and 16 serious adverse events were reported in nine (17%) of 53 patients from the high-dose group. The most common treatment-related adverse events in both groups were infusion site pain and other infusion site reactions. Treatment with subcutaneous treprostinil was safe, and improved exercise capacity in patients with severe CTEPH. Subcutaneous treprostinil provides a parenteral treatment option for patients of WHO functional class III or IV and those who do not tolerate other therapies or need combination treatment. SciPharm Sàrl.

Balloon pulmonary angioplasty for the treatment of residual or recurrent pulmonary hypertension after pulmonary endarterectomy

BackgroundPulmonary endarterectomy (PEA) is the treatment of choice for chronic thromboembolic pulmonary hypertension (CTEPH). However, persistent pulmonary hypertension continues in 5–35% of patients after PEA. Recently, balloon pulmonary angioplasty (BPA) showed promise as a strategy for patients with non-operable CTEPH. Therefore, we investigated the usefulness of BPA for residual pulmonary hypertension after PEA. MethodsFifteen patients with residual pulmonary hypertension after PEA received 71 BPA sessions (4.7 ± 1.4 sessions/patient). The mean time between the PEA and the first BPA session was 28.1 ± 25.8 months. All patients underwent a comprehensive diagnostic work-up, including right heart catheterization, functional and laboratory tests, before, and 6–4 weeks after the BPA sessions. ResultsAfter BPA, the mean pulmonary arterial pressure decreased from 44.7 ± 6.4 to 30.8 ± 7.5 mm Hg (31% decline; p < 0.001). Pulmonary vascular resistance decreased from 551.9 ± 185.2 to 343.8 ± 123.8 dyn∗s/cm−5 (38% decline; p < 0.001). The 6-min walking distance increased from 383 ± 104 to 476 ± 107 m (mean change +93 m; p < 0.001). In two sessions (2.8%), serious periprocedural complications occurred. During a mean follow-up of 18 ± 14.3 months, one patient died two months after the last BPA session. Fourteen patients survived. ConclusionsBPA could be a promising therapeutic strategy for persistent pulmonary hypertension after PEA in patients with CTEPH.

Poor Subpleural Perfusion Predicts Failure After Balloon Pulmonary Angioplasty for Nonoperable Chronic Thromboembolic Pulmonary Hypertension

Poor subpleural perfusion (PSP) in the capillary phase of pulmonary angiography predicts worse outcomes following pulmonary endarterectomy in operable chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) has emerged as a treatment for nonoperable CTEPH. The goal of the present article was to assess the association between PSP and BPA failure. Subpleural perfusion was classified as poor (defined as subpleural spaces either not perfused or minimally perfused in all segments) or normal. We retrospectively reviewed PSP and hemodynamic variables of 101 consecutive patients who underwent BPA from February 2014 to August 2016. The total cross-sectional area of bronchial arteries was also measured by using CT scanning. Patients were categorized according to hemodynamic results after the last BPA: a failure group (defined as mean pulmonary arterial pressure > 30mmHg and a decrease in pulmonary vascular resistance< 30%[n= 15]) or a success group (n= 86). Although baseline hemodynamic variables were similar between the two groups, PSP was observed in 46.7%of patients in the failure group vs13.9%in the success group (P=.003). Multivariate analysis revealed that PSP was the only predictor of BPA failure (OR, 4.02 [95%CI, 1.17-13.89]; P= .028). Patients with PSP exhibited poorly developed bronchial arteries compared with patients with normal perfusion (7.0 [5.8-9.6] mm2 vs8.7 [6.9-11.3] mm2; P= .032). PSP in the capillary phase, suggesting the presence of small vessel disease with diffuse distal thrombosis, is a predictor of BPA failure. PSP was also associated with less developed bronchial arteries, which suggests a key role of bronchial-pulmonary anastomoses in maintaining the pulmonary capillary bed open downstream of the pulmonary arterial obstruction. PSP affected approximately 15%of patients with nonoperable CTEPH who underwent BPA.

P4005Poor subpleural perfusion as a predictor of failure after balloon pulmonary angioplasty for non-operable chronic thromboembolic pulmonary hypertension

P4005Poor subpleural perfusion as a predictor of failure after balloon pulmonary angioplasty for non-operable chronic thromboembolic pulmonary hypertension

5017Subcutaneous treprostinil for the treatment of non-operable chronic thromboembolic pulmonary hypertension: a randomized, controlled trial (CTREPH)

5017Subcutaneous treprostinil for the treatment of non-operable chronic thromboembolic pulmonary hypertension: a randomized, controlled trial (CTREPH)

Dead-space ventilation is linked to exercise capacity and survival in distal chronic thromboembolic pulmonary hypertension

Cardiopulmonary exercise testing (CPET) is frequently used for the evaluation of patients with pulmonary hypertension (PH). Non-operable distal chronic thromboembolic pulmonary hypertension (CTEPH) represents a unique subgroup of PH where microvascular disease resembling pulmonary arterial hypertension (PAH) may predominate and efficacious medical therapy is now available. However, little is known regarding the detailed CPET profile of patients with distal CTEPH, and whether ventilation and gas exchange responses are different from PAH. Forty-nine consecutive patients with non-operable distal CTEPH according to multidisciplinary team assessment and 45 PAH patients underwent CPET and right heart catheterization. Patients were followed up for a median of 3.2 years (interquartile range: 1.8 to 4.4). Pulmonary hemodynamics were similar in distal CTEPH and PAH groups, but patients with distal CTEPH achieved a lower percent predicted peak oxygen consumption (59 ± 13% vs 66 ± 14%, p < 0.05). At peak exercise, higher physiologic dead-space fraction (VD/VT) (0.45 ± 0.07 vs 0.35 ± 0.07, p < 0.0001) and higher arterial-to-end-tidal carbon dioxide gradient (9 ± 3 vs 5 ± 3 mm Hg, p < 0.0001) were observed in distal CTEPH compared with PAH. Ventilatory efficiency, expressed as VE/VCO2 slope, was also more impaired in distal CTEPH (52.2 ± 10.1 vs 43.8 ± 8.4 liters/min, p < 0.0001). In the distal CTEPH group only, higher VD/VT was associated with lower peak oxygen consumption (r = -0.46, p = 0.003) and worse survival. Compared with PAH, a distinct pattern of response to exercise was observed in distal CTEPH, characterized by increased dead-space ventilation that resulted in worse ventilatory efficiency and greater impairment of exercise capacity. In distal CTEPH, dead-space ventilation correlated with exercise capacity and was associated with survival.

High prevalence of severe coronary artery disease in elderly patients with non-operable chronic thromboembolic pulmonary hypertension referred for balloon pulmonary angioplasty.

IntroductionBalloon pulmonary angioplasty (BPA) is a new emerging catheter-based alternative treatment option for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).AimTo show that all elderly CTEPH patients referred for BPA are at higher risk of obstructive coronary artery disease and that, in daily practice, they should undergo invasive coronary angiography.Material and methodsEleven patients at the age of at least 65 years (6 males, 5 females, 77.2 ±5.9 years) with confirmed non-operable type II or type III CTEPH, considered for BPA, underwent elective coronary angiography. Severe obstructive coronary artery disease (CAD) was diagnosed when stenosis of left main coronary artery ≥ 50% or stenosis of ≥ 70% of epicardial arteries was angiographically confirmed. We also screened for CAD consecutive age- and sex-matched 114 PE survivors (52 males, 62 females, 74.8 ±7.2 years) with excluded CTEPH.ResultsSevere CAD was more frequent in elderly patients with non-operable type II or type III CTEPH candidates for BPA than in elderly acute PE survivors with excluded CTEPH (54.5% vs. 16.7%, p < 0.01), and therefore elderly CTEPH patients referred for BPA were at higher risk of CAD (OR = 5.9, 95% CI: 1.64–21.46, p = 0.007) when compared to elderly survivors after acute PE with excluded CTEPH.ConclusionsAll elderly CTEPH patients referred for BPA are at higher risk of severe CAD and should routinely undergo invasive coronary angiography before BPA.

High perfusion pressure as a predictor of reperfusion pulmonary injury after balloon pulmonary angioplasty for chronic thromboembolic pulmonary hypertension

BackgroundClinical efficacy of balloon pulmonary angioplasty (BPA) to the patients with non-operable chronic thromboembolic pulmonary hypertension (CTEPH) for improving pulmonary hemodynamics and exercise tolerance has been reported in these several years. However, reperfusion pulmonary injury (RPI) remains to be a major complication of BPA to overcome. This study elucidated the local predictor of RPI. MethodsTwenty-eight consecutive patients with non-operable CTEPH underwent BPA for lesions in the segmental or sub-segmental vessels. Pre- and post-BPA pulmonary arterial pressures at proximal (Pp) and distal (Pd) to the stenosis were measured by a 0.014-in. pressure wire. Positive or negative RPI was evaluated by chest computed tomography in each re-perfused segment separately 4h after BPA. ResultsPressure measurements pre- and post-BPA were obtained from 110 lesions, where Pd and pressure ratio (Pd/Pp) increased after BPA in all lesions. Among them, RPI was observed in 49 lesions (44.5%). In the RPI-positive lesions, post-BPA Pd and post-BPA Pd/Pp were higher compared with the RPI-negative lesions. Multivariate logistic analysis revealed that the post-BPA Pd was independently associated with RPI incidence. Receiver operating characteristic curve analysis demonstrated the best cut-off value of 19.5mmHg for post-BPA Pd to predict RPI. ConclusionsHigh reperfusion pressure after BPA could be a predictor of RPI. Monitoring local pressure during BPA procedure may have a potential to reduce the incidence of RPI.