Residual Chronic Thromboembolic Pulmonary Hypertension Research Articles

Status and Future Directions for Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Disease With and Without Pulmonary Hypertension: A Scientific Statement From the American Heart Association.

Balloon pulmonary angioplasty continues to gain traction as a treatment option for patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. Recent European Society of Cardiology guidelines on pulmonary hypertension now give balloon pulmonary angioplasty a Class 1 recommendation for inoperable and residual chronic thromboembolic pulmonary hypertension. Not surprisingly, chronic thromboembolic pulmonary hypertension centers are rapidly initiating balloon pulmonary angioplasty programs. However, we need a comprehensive, expert consensus document outlining critical concepts, including identifying necessary personnel and expertise, criteria for patient selection, and a standardized approach to preprocedural planning and establishing criteria for evaluating procedural efficacy and safety. Given this lack of standards, the balloon pulmonary angioplasty skill set is learned through peer-to-peer contact and training. This document is a state-of-the-art, comprehensive statement from key thought leaders to address this gap in the current clinical practice of balloon pulmonary angioplasty. We summarize the current status of the procedure and provide a consensus opinion on the role of balloon pulmonary angioplasty in the overall care of patients with chronic thromboembolic pulmonary disease with and without pulmonary hypertension. We also identify knowledge gaps, provide guidance for new centers interested in initiating balloon pulmonary angioplasty programs, and highlight future directions and research needs for this emerging therapy.

Patient selection for balloon pulmonary angioplasty: Six-year results from a high volume PTE surgical center.

Chronic thromboembolic pulmonary hypertension (CTEPH) is the result of incompletely resolved pulmonary emboli (PE) that lead to chronic right heart failure. The two mechanical treatment options are pulmonary thromboendarterectomy (PTE) and balloon pulmonary angioplasty (BPA). There are no formal criteria for BPA patient selection and treatment decisions vary according to a center's experience with BPA and PTE. We performed a retrospective review of consecutive patients treated with PTE and BPA at UCSD from March 2015 to 2021. Clinical and hemodynamic data were collected. Patients were categorized according to the rationale for BPA. One hundred fifty three patients underwent 643 BPA sessions, and 1104 patients underwent PTE. Patients selected for PTE had worse baseline hemodynamics with mean pulmonary artery pressure 41.1 ± 11.7 versus 34.6 ± 11.2 mmHg, p < 0.001. 59% of patients selected for BPA had surgically inaccessible disease, 21% had residual CTEPH after PTE, 10% had a discordance between disease burden and symptoms/hemodynamics, 7% had comorbidities that prevented PTE and 3% refused PTE surgery. 28% of patients who underwent PTE had exclusively level III or IV disease based on surgical specimen. There were no BPA procedure-related mortalities and minor pulmonary vascular complication rates during BPA were 9.2%. The most common reason for BPA selection was surgically inaccessible disease followed by residual CTEPH after PTE. Almost one third of patients who underwent PTE had exclusively distal disease by surgical criteria and might have been directed to BPA at a less experienced surgical center.

Noninvasive follow-up strategy after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension.

BackgroundThe success of pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is usually evaluated by performing a right heart catheterisation (RHC). Here, we investigate whether residual pulmonary hypertension (PH) can be sufficiently excluded without the need for a RHC, by making use of early post-operative haemodynamics, or N-terminal pro-brain natriuretic peptide (NT-proBNP), cardiopulmonary exercise testing (CPET) and transthoracic echocardiography (TTE) 6 months after PEA.MethodsIn an observational analysis, residual PH after PEA measured by RHC was related to haemodynamic data from the post-operative intensive care unit time and data from a 6-month follow-up assessment including NT-proBNP, TTE and CPET. After dichotomisation and univariate analysis, sensitivity, specificity, positive predictive value, negative predictive value (NPV) and likelihood ratios were calculated.ResultsThirty-six out of 92 included patients had residual PH 6 months after PEA (39%). Correlation between early post-operative and 6-month follow-up mean pulmonary artery pressure was moderate (Spearman rho 0.465, p<0.001). Early haemodynamics did not predict late success. NT-proBNP >300 ng·L−1 had insufficient NPV (0.71) to exclude residual PH. Probability for PH on TTE had a moderate NPV (0.74) for residual PH. Peak oxygen consumption (V′O2) <80% predicted had the highest sensitivity (0.85) and NPV (0.84) for residual PH.ConclusionsCPET 6 months after PEA, and to a lesser extent TTE, can be used to exclude residual CTEPH, thereby safely reducing the number of patients needing to undergo re-RHC after PEA.

Balloon Pulmonary Angioplasty in Patients With Inoperable or Recurrent/Residual Chronic Thromboembolic Pulmonary Hypertension: A Single-Centre Initial Experience

Patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) are often treated with pulmonary arterial hypertension-specific drugs. However, most of these patients remain symptomatic, despite medical treatment. Balloon pulmonary angioplasty (BPA) is an emerging therapeutic intervention for patients with inoperable CTEPH. This study aimed to report the initial experience of BPA in a tertiary referral centre for CTEPH. A total of 26 consecutive patients, who underwent 91 BPA sessions, were included in the study. All patients underwent a detailed examination, including 6-minute walking distance (6MWD), and right heart catheterisation at baseline and 3 months after the last BPA session. The mean age of the patients was 51±17 years. Fifteen (15) patients had inoperable CTEPH and 11 patients had residual or recurrent CTEPH post pulmonary endarterectomy (PEA). Functional class improved in 17 of 26 (65%) patients. The 6MWD increased from a mean 315±129 to 411±140 m (p<0.001), and NT pro-BNP reduced from a median 456 to 189 pg/mL (p=0.001). The number of patients who required supplemental oxygen decreased from 11 (42.3%) to five (19%) (p=0.031) after BPA treatment. The mean pulmonary artery pressure decreased from a mean 47.5±13.4 to 38±10.9 mmHg (p<0.001), the pulmonary vascular resistance decreased from a mean 9.3±4.7 to 5.8±2.8 Wood units (p<0.001), and the cardiac index increased from a mean 2.4±0.7 to 2.9±0.6 L/min/m2 (p=0.008). Balloon pulmonary angioplasty improved haemodynamics, 6MWD, and functional class, and reduced the requirement for supplemental oxygen, with an acceptable risk-benefit ratio in patients with inoperable CTEPH and with residual/recurrent CTEPH.

REPLACE and the role of riociguat in pulmonary arterial hypertension therapy

Following completion of the randomised placebo-controlled study of riociguat for the treatment of inoperable or residual chronic thromboembolic pulmonary hypertension, 1 Simonneau G D'Armini AM Ghofrani HA et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension: a long-term extension study (CHEST-2). Eur Respir J. 2015; 45: 1293-1302 Crossref PubMed Scopus (195) Google Scholar riociguat became the only vasodilator therapy approved by the US Food and Drug Administration to treat this difficult disease, and accordingly plays a substantive role in therapy for those with WHO Group 4 pulmonary hypertension. On the basis of the robust results of the Pulmonary Arterial Hypertension Soluble Guanylate Cyclase-Stimulator Trial 1 (PATENT-1) study, 2 Ghofrani HA Galie N Grimminger F et al. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013; 369: 330-340 Crossref PubMed Scopus (928) Google Scholar in which 194 (44%) of 443 participants were on background therapy with an endothelin receptor antagonist, riociguat also received approval for the treatment of pulmonary arterial hypertension (PAH). Availability of riociguat for PAH raised questions about its role compared with that of phosphodiesterase-5 inhibitors (PDE5i; sildenafil and tadalafil), which also act on the nitric oxide pathway, are the most widely prescribed therapy for PAH, and have generic, cost-effective versions available. Without head-to-head studies, comparison of these agents is challenging. Switching to riociguat versus maintenance therapy with phosphodiesterase-5 inhibitors in patients with pulmonary arterial hypertension (REPLACE): a multicentre, open-label, randomised controlled trialSwitching to riociguat from PDE5i treatment, both of which act via the nitric oxide–soluble guanylate cyclase–cyclic guanosine monophosphate pathway, could be a strategic option for treatment escalation in patients with PAH at intermediate risk of 1-year mortality. Full-Text PDF

Pulmonary Artery Denervation for Patients With Residual Pulmonary Hypertension After Pulmonary Endarterectomy

BackgroundPulmonary artery denervation (PADN) procedure has not been applied to patients with residual chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary endarterectomy (PEA). ObjectivesThis study sought to assess the safety and efficacy of PADN using remote magnetic navigation in patients with residual CTEPH after PEA. MethodsFifty patients with residual CTEPH despite medical therapy at least 6 months after PEA, who had mean pulmonary artery pressure ≥25 mm Hg or pulmonary vascular resistance (PVR) > 400 dyn‧s‧cm−5 based on right heart catheterization were randomized to treatment with PADN (PADN group; n = 25) using remote magnetic navigation for ablation or medical therapy with riociguat (MED group; n = 25). In the MED group, a sham procedure with mapping but no ablation was performed. The primary endpoint was PVR at 12 months after randomization. Key secondary endpoint included 6-min walk test. ResultsAfter PADN procedure, 2 patients (1 in each group) developed groin hematoma that resolved without any consequences. At 12 months, mean PVR reduction was 258 ± 135 dyn‧s‧cm−5 in the PADN group versus 149 ± 73 dyn‧s‧cm−5 in the MED group, mean between-group difference was 109 dyn‧s‧cm−5 (95% confidence interval: 45 to 171; p = 0.001). The 6-min walk test distance was significantly increased in the PADN group as compared to distance in the MED group (470 ± 84 m vs. 399 ± 116 m, respectively; p = 0.03). ConclusionsPADN in patients with residual CTEPH resulted in substantial reduction of PVR at 12 months of follow-up, accompanied by improved 6-min walk test.

A clinical case of radiofrequency pulmonary artery denervation for treatment of a patient with residual chronic thromboembolic pulmonary hypertension

Improving the methods of diagnosis, therapy and surgical treatment of chronic thromboembolic pulmonary hypertension (CTEPH) provides a complete cure in most cases. Data on the survival of CTELH patients is contradictory, and primarily due to the treatment availability. In Russian Federation there are few experienced centers performing thromboendarterectomy and balloon pulmonary angioplasty. Until recently, specific drug therapy was not available for most patients because of its high cost. The presented clinical case demonstrates modern opportunities of treatment of inoperable patients with residual CTEPH by the method of pulmonary artery denervation using a radiofrequency ablation.

Prognostic Value of Oxidative Stress Markers in Patients with Pulmonary Arterial or Chronic Thromboembolic Pulmonary Hypertension.

Oxidative stress is regarded to play a crucial role in the pathophysiology of pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). This study evaluated the prognostic value of serum oxidative stress markers (malondialdehyde (MDA), total antioxidant capacity (TAC), catalase activity (CAT), and superoxide activity (SOD)) in patients with PAH and CTEPH (n = 45). During 13 months of follow-up (median 9 months), clinical deterioration occurred in 14 patients (including 2 deaths). On the Cox regression analysis, MDA, TAC, and CAT were associated with clinical deterioration (p = 0.0068, HR = 1.42, 95% CI: 1.10-1.82; p = 0.0038, HR = 0.033, 95% CI: 0.0032-0.33; and p = 0.046, HR = 0.20, 95% CI: 0.04-0.98, respectively). There was no significant difference in SOD (p = 0.53, HR = 0.97, 95% CI: 0.87-1.08). The cut-off value derived from ROC curve analysis was 3.79 μM (p = 0.0048, AUC = 0.76, 95% CI: 0.62-0.91) for MDA, 0.49 mM (p = 0.027, AUC = 0.71, 95% CI: 0.18-0.47) for TAC, and 1.34 U/L (p = 0.029, AUC = 0.71, 95% CI: 0.55-0.86) for CAT. MDA in the group with deterioration was higher (p = 0.0041), while TAC as well as CAT were lower (p = 0.027 and p = 0.028, respectively) when compared to stable patients. Survival without clinical deterioration was significantly longer in patients with lower MDA (p = 0.037, HR = 0.37, 95% CI: 0.12-1.14, log-rank), higher TAC (p = 0.0018, HR = 0.19, 95% CI: 0.06-0.60, log-rank), and higher CAT (p = 0.044, HR = 0.31 95% CI: 0.11-0.88, log-rank). Markers of oxidative stress such as MDA, TAC, and CAT were associated with adverse clinical outcomes in patients with PAH and inoperable or residual CTEPH.

4282Pulmonary artery denervation in patients with residual pulmonary hypertension after pulmonary endarterectomy: one-year results of the first -in-man, sham-controlled, pilot randomized clinical trial

Abstract Background Pulmonary endarterectomy (PE) is the method of choice in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Despite the positive effect after surgery combined with medical treatment, 10–40% of patients develop residual CTEPH. Pulmonary artery denervation (PAD) is a novel treatment in PAH with optimistic results but was not tested in patients with residual CTEPH. Objective To assess the safety and efficacy of PAD using remote magnetic navigation system in patients with residual CTEPH after PE. Methods 278 patients with CTEPH after PE were screened. 50 patients (mean age 47.6±14.3, 50% female) with a history of residual CTEPH (a resting pulmonary artery pressure ≥25 mm Hg or pulmonary vascular resistance &gt;400 dyn sec cm–5 despite medical therapy 6 months after PE) were randomized into two groups: PAD (n=25; PAD group) or medical therapy with riociguat (n=25; MED group). In both groups right heart catheterization (RHC)was performed after randomization. In the PAD group, remote magnetic navigation systemwas used to target sympathetic nerve fibers, located near bifurcation and ostia of the main brunches of right and left pulmonary arteries. This study was conducted as double-blind and sham-controlled and the primary endpoint was change in pulmonary vascular resistance (PVR) by RHC at 12 months. Secondary endpoints included 6-minute walk test (6MWT), pulmonary artery pressure, and clinical outcomes. All patients were followed for 12 months after randomization. Unpaired t-test and Fisher's exact test were used for between-group comparisons of continuous and categorical variables, respectively. A p value of less than 0.05 was considered statistically significant. Results Two patients (one in each group) developed groin hematoma which resolved without any consequences. At the end of 12 month, the PVR was significantly low in PAD group as compared with MED group (343±149 dyn sec cm–5 vs 444±145 dyn sec cm–5, respectively; mean difference −101, 95% confidence interval: −193 to −10; p=0.032). The mean, systolic and diastolic PA pressure was also reduced significantly in PAD group compared to MED group (25.8±7.3mm Hg vs 33.8±6.4 mm Hg, 46.2±14.1mm Hg vs 54.2±8.1 mm Hg,13.2±5.3mm Hg vs 20.2±4.8mm Hg; p&lt;0.001, p=0.002, p&lt;0.001, respectively). The PAD group demonstrated significant improvement of the 6MWT over MED group (470±84 m vs 399±116 m, respectively, p=0.031). In the PADN group 1 (4%) patient was hospitalized due to heart failure progression compared to 7 (29%) patients in MED group (p=0.049). One patient in PAD group and two patients in MED group died. Conclusions Pulmonary artery denervation in patients with residual pulmonary hypertension was safe and effective, and resulted in substantial reduction of pulmonaryvascular resistance and pulmonary artery pressure during 12 months follow up, accompanied by improved 6-minute walk test and reduced need for hospitalization. Clinical Trials Registration: NCT02745106 Acknowledgement/Funding Grant from Biosense Webster

P2776Radiofrequent pulmonary artery denervation - alternative treatment of residual chronic thromboembolic pulmonary hypertension. Results of a randomized pilot study

Abstract Background/Introduction Pulmonary endarterectomy (PEA) is the gold standard of CTEPH treatment. However, residual CTEPH develops in 10–40% of patients after PEA, which leads to progression of right ventricular insufficiency. Currently, the only way to treat residual CTEPH is PAH-specific drug therapy. However, this treatment is not indicated for all patients because of the arterial hypotension and dyspeptic disorders. Purpose To assess the safety and efficacy of radiofrequent pulmonary artery denervation (PADN) in patients with residual CTEPH after PEA. Methods In 2015, a randomized pilot study was conducted to evaluate PADN in patients with residual CTEPH (NCT 02745106). 278 patients with CTEPH after PEA were screened. In 62 of them, according to the echocardiography, residual CTEPH (systolic pulmonary artery pressure (PAP) ≥45 mm Hg) was detected. In 50 patients, residual CTEPH was confirmed during right heart catheterization (RHC): mean PAP ≥25 mmHg and pulmonary vascular resistance (PVR) &gt;400 dyn s cm–5. Patients were randomized into two groups: 25 in PADN group and 25 in drug therapy group with riociguat. Mean age was 39 years [26; 51]. The mean duration after PEA was 4.5 years [1; 8.5]. The primary end point was PVR in the short-term and long-term follow-up. Secondary end points were: mean PAP, cardiac output, 6-minute walk test (6MWD) and NYHA functional class. All patients were followed up for 12 months after discharge. The PADN procedure was performed using electrophysiological catheter Navistar RMT Thermocool, Biosense Webster, Diamond Bar, CA, USA and non-fluroscopic 3D navigation system. Results There was no mortality. In two patients (one in each group) hematoma developed in femoral vein puncture site without any consequences. The mean surgery time was 105 [93; 120] minutes. After 12 months, PVR was significantly lower in the PADN group compared with the drug treatment group (343±149 dyn s cm–5 vs 444±145 dyn s cm–5, respectively; mean difference −101, 95% confidence interval from −193 to −10; p=0.032). The mean PAP was also significantly lower in the PADN group (25.8±7.3 mm Hg vs. 33.8±6.4 mm Hg, p&lt;0.001). We noticed a significant improvement of 6MWD test in PADN group compared with the drug treatment group (470±84 m versus 399±116 m, respectively, p=0.031). In PADN group 1 (4%) patient was hospitalized due to progression of heart failure compared with 7 patients (29%) in the drug treatment group (p=0.049). One patient (4%) in the PADN group and two patients (8%) in the drug treatment group died due to progression of heart failure over the long-term follow-up. Conclusions The PADN technique showed its safety and efficacy in the treatment of patients with residual CTEPH and can be used in clinical practice. The obtained first results showed that the proposed PADN, together with optimal medical therapy, can take a place in the treatment of residual CTEPH after PEA.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension: Initial Single-Center Experience.

ObjectiveTo evaluate the safety and efficacy of balloon pulmonary angioplasty (BPA) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) seen at a US medical center.Patients and MethodsPatients with inoperable or residual postendarterectomy CTEPH who underwent BPA at Mayo Clinic in Rochester, Minnesota, between August 11, 2014, and May 17, 2018, were included. Invasive hemodynamic, clinical, laboratory, and echocardiographic data were collected and analyzed retrospectively.ResultsWe identified 31 patients (26 with inoperable CTEPH and 5 with residual postendarterectomy CTEPH) who underwent 75 BPA procedures performed in a staged manner to reduce complications. The median number of sessions was 2 (interquartile range [IQR], 1-3) per patient, and the number of vessels treated per session was 3 (IQR, 2-3). Of the 31 patients, 24 (77.4%) were taking pulmonary vasodilators and 22 (71.0%) were taking riociguat. The mean pulmonary arterial pressure decreased from 40 mm Hg (IQR, 29-48 mm Hg) to 29 mm Hg (IQR, 25-37 mm Hg; P<.001); pulmonary vascular resistance decreased from 5.5 Wood units (WU) (IQR, 3.0-7.6 WU) to 3.3 WU (2.2-5.2 WU; P<.001). The follow-up 6-minute walk test was performed in 13 patients and improved from 402 m (IQR, 311-439 m) to 439 m (366-510 m; P=.001). Of the 31 patients, 19 (61.3%) had improvement in New York Heart Association functional class. The mean ± SD nadir of minute ventilation/carbon dioxide production decreased by 3.4±5.5 (P=.03), reflecting improved ventilatory efficiency. Complications included hemoptysis requiring overnight intensive care unit observation (n=1) and cardiac tamponade requiring pericardiocentesis (n=1). One patient had reperfusion injury requiring intubation, recovered, and was dismissed to home but died unexpectedly within less than 30 days of the procedure. Serious complications occurred in 3 of the 75 BPA procedures (4.0%).ConclusionOur experience with BPA revealed that this procedure has acceptable risk and improves hemodynamics, functional class, and exercise tolerance in patients with inoperable or residual CTEPH.

Long-term clinical value and outcome of riociguat in chronic thromboembolic pulmonary hypertension

BackgroundTo improve clinical outcome, patients with inoperable and residual chronic thromboembolic pulmonary hypertension (CTEPH) can be treated with riociguat. The aim of this study is to explore long-term outcomes and to compare our ‘real world’ data with previous research. MethodsWe included all consecutive patients with technical inoperable and residual CTEPH, in whom riociguat therapy was initiated from January 2014 onwards, with patients followed till January 2019. Survival, clinical worsening (CW), functional class (FC), N-terminal pro brain natriuretic peptide (NT-proBNP) and 6-minute walking distance (6MWD) were described yearly after riociguat initiation. ResultsThirty-six patients (50% female, mean age 64.9 ± 12.1 years, 54% WHO FC III/IV and 6MWD 337 ± 138 m could be included, with a mean follow-up of 2.3 ± 1.2 years. Survival and CW-free survival three years after initiation of riociguat were 94% and 78%, respectively. The 6MWD per 10 m at baseline was a significant predictor (HR 0.90 [0.83–0.97], p = 0.009) for CW. At three years follow-up the WHO FC and 6MWD improved and NT-proBNP decreased compared to baseline. ConclusionOur study confirms that riociguat is an effective treatment in patients with technical inoperable and residual CTEPH at long-term follow-up. Although our results are consistent with previous studies, more ‘real world’ research is necessary to confirm long-term results.

Treatment of patients with chronic thrombo&amp;shy;embolic pulmonary hypertension: focus on riociguat

Chronic thromboembolic pulmonary hypertension (CTEPH) is a disease of the pulmonary vascular bed that is characterized by elevations in the mean pulmonary artery pressure in the setting of perfusion defects on ventilation–perfusion scan, and subsequently confirmed by pulmonary angiography. CTEPH, or World Health Organization (WHO) group 4 pulmonary hypertension, is a result of unresolved thromboembolic obstruction in the pulmonary arteries. Pulmonary endarterectomy (PEA) is the treatment of choice for CTEPH as it is a potentially curative therapy. However, up to one-third of patients are not candidates for the surgery, either due to distal and inaccessible nature of the lesions or comorbid conditions. Due to remodeling that occurs in nonobstructed pulmonary vessels, a portion of patients who have undergone PEA have residual CTEPH after the procedure, attributable to high shear stress prior to PEA. This phenomenon has led to the understanding of a so-called “two-compartment model” of CTEPH, opening the door to pharmacologic treatment strategies. In 2013, riociguat, a soluble guanylate cyclase stimulator, was approved in the US and Europe for the treatment of inoperable or persistent/recurrent CTEPH. This article reviews the current management of CTEPH with a focus on riociguat.

Treatment of pulmonal hypertension

While the clinical classification of diseases with pulmonary hypertension (PH) has remained fairly stable in recent years, the treatment options have improved significantly. In addition to the General measures (vaccinations, physical training) new recommendations for supportive therapy (administration of diuretics, iron supplementation and oral anticoagulant) exist currently. Some new substances (mostly in the indication pulmonary arterial hypertension) have been admitted to the targeted drug treatment in recent years. For the first time, exist a approved drug therapy for the non-operable and residual chronic thromboembolic pulmonary hypertension.

Clinical and Economic Analysis Riotsiguata in Patients With Unresectable or Residual Chronic Thromboembolic Pulmonary Hypertension

to undertake economic evaluation of riociguat in comparison with standard practice of treating patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH) in Russian healthcare. Standard practice was revealed by means of peer interview. It comprised bosentan monotherapy with addition of sildenafil in case of disease progression. Difference in efficacy between riociguat and bosentan was established through the indirect comparison based on the results of randomized controlled trials. Difference in costs of CTEPH treatment with riociguat and standard practice eas estimated in the Markov model that simulated changes in disease functional class (FC). Direct medical costs were considered and included drugs prescriptions, in-patient and out-patient medical care. Probabilistic sensitivity analysis was conducted. The results of indirect comparison suggest statistically significant higher probability of favorable outcomes in case of treatment with riociguat: improvement by more or equal 1 FC (difference in proportions =14.8% with 95% confidence interval from 0.1 to 29.5; p=0.048) and increase of distance in 6-minute walking distance (mean difference =42.9 m with 95% confidence interval from 10.5 to 75.3; p=0.009). In base-case scenario difference in costs between riociguat and standard practice was 60 646.15 RUB per 1 patient per year in favor of the former. Riociguat costs were lower in 94.4% of sensitivity analysis cycles. In 72.5% of sensitivity analysis cycles costs difference in favor of riociguat was at least half of that in in base-case. In 47.3% of sensitivity analysis costs difference in favor of riociguat was equal or higher to that in base-case. The results of modeling suggest that in Russian healthcare treatment of CTEPH with riociguat is characterized by higher efficacy at lower costs.

Home-based pulmonary rehabilitation in patients with inoperable or residual chronic thromboembolic pulmonary hypertension: a preliminary study.

Management of chronic thromboembolic pulmonary hypertension (CTEPH) has recently improved because of advances in pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), and disease-targeted medications. However, patients with inoperable CTEPH or persistent pulmonary hypertension (PH) after these interventions continue to exhibit impaired exercise capacity and limited quality of life (QOL). Eight patients with inoperable or residual CTEPH (mean age, 64±12 years; WHO functional class II/III, 6/2; mean pulmonary artery pressure, 47±13 mmHg) in stable condition and receiving disease-targeted medications participated in a 12-week home-based pulmonary rehabilitation program (muscle strength training, respiratory exercises, and walking) with supervised hospital sessions from March 2012 to January 2014. Efficacy parameters were prospectively evaluated at baseline and at completion of the 12-week program. After completion of the pulmonary rehabilitation program, the 6-minute walking distance (6MWD) (33.3±25.1 m), St. George׳s Respiratory Questionnaire activity score, quadriceps force, and 7-day physical activity level were significantly improved compared with baseline. All subjects completed the rehabilitation program. Although one patient experienced presyncope during the in-hospital exercise sessions, no other severe adverse events or complications of pulmonary rehabilitation were observed. These findings suggest that home-based pulmonary rehabilitation with closely supervised sessions may safely improve exercise capacity, leg muscle strength, general activity in daily life and health-related QOL in CTEPH patients.

Phase III success for first-in-class pulmonary hypertension drug

Data presented at the recent annual conference of the American College of Chest Physicians (ACCP) by Bayer for its oral soluble guanylyl cyclase (sGC) stimulator riociguat generated high hopes for the drug's potential in the treatment of pulmonary hypertension (PH). The primary end points were met in both of the pivotal Phase III studies, in which riociguat was evaluated in patients with pulmonary arterial hypertension (PAH) or in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH).

Exercise Training Improves Exercise Capacity and Quality of Life in Patients with Inoperable or Residual Chronic Thromboembolic Pulmonary Hypertension

BackgroundAim of this prospective study was to evaluate the effects of exercise training in patients with inoperable or residual chronic thromboembolic pulmonary hypertension (CTEPH).MethodsThirty-five consecutive patients with invasively confirmed inoperable or residual CTEPH (16 women;19 men; mean age 61±15 years, mean pulmonary artery pressure, 63±20 mmHg; primary inoperable n = 33, persisting pulmonary hypertension after pulmonary endarterectomy n = 2) on stable disease-targeted medication received exercise training in-hospital for 3 weeks and continued at home for 15 weeks. Medication remained unchanged during the study period. Efficacy parameters have been evaluated at baseline, after 3 and 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of median 36.4 months (interquartile range 26.6–46.6 months).ResultsAll patients tolerated exercise training without severe adverse events. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 61±54 meters after 3 weeks (p<0.001) and by 71±70 meters after 15 weeks (p = 0.001), as well as scores of quality-of-life questionnaire, peak oxygen consumption and maximal workload. NT-proBNP improved significantly after 3 weeks of exercise training (p = 0.046). The 1-year survival rate was 97%, 2-year survival rate was 94% and the 3-year-survival 86% respectively.ConclusionTraining as add-on to medical therapy may be effective in patients with CTEPH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further multicentric randomized controlled studies are needed to confirm these promising results.Trial RegistrationClinicalTrials.gov NCT01398345

S97 Inflammatory cytokines are elevated in patients with operable chronic thromboembolic pulmonary hypertension and predict outcome post-endarterectomy

RationaleElevated levels of inflammatory cytokines have been reported in patients with idiopathic pulmonary arterial hypertension. The role of inflammation in chronic thromboembolic pulmonary hypertension (CTEPH) is largely unknown. We sought...

Pulmonary arterial size and response to sildenafil in chronic thromboembolic pulmonary hypertension

BackgroundRelative area change (RAC) of the proximal pulmonary artery is a measurement of pulmonary artery distensibility and has been shown to correlate with vasoreactivity studies in patients with idiopathic pulmonary arterial hypertension. We have previously noted a relationship between invasive hemodynamic vasoreactivity testing and long-term response to sildenafil in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). We therefore set out to determine whether RAC can provide useful correlatory non-invasive data.MethodsPatients recruited to a randomized, controlled trial (RCT) of sildenafil at 40 mg 3 times daily underwent additional magnetic resonance imaging (MRI) at the baseline of the trial. Eighteen patients had an MRI that led to a diagnosis of inoperable distal CTEPH or significant residual CTEPH post-operatively. The primary end-point was improvement in 6-minute walk test (6MWT) with secondary end-points of right heart catheterization–based hemodynamics, N-terminal pro–brain natriuretic peptide (NT pro-BNP) and functional class. RAC assessed by MRI was correlated with trial end-points.ResultsFourteen subjects with baseline MRI completed the protocol. RAC was the only baseline variable that correlated at 1 year to the primary end-point of improvement in 6MWT (r = 0.7, p = 0.006), and also to a change in NT pro-BNP (r = 0.59, p = 0.03). Using a cut-off of RAC over 20% there was an 87.5% sensitivity (95% confidence interval [CI]: 45% to 100%) and a 66.7% specificity (95% CI: 22% to 96%) for an improvement in 6MWT of >40 meters.ConclusionsRAC correlates with functional response to sildenafil, as measured by the 6MWT, and improved heart function, as measured by NT pro-BNP. RAC shows potential in understanding and possibly predicting treatment response.