The efficacy of bosentan in inoperable chronic thromboembolic pulmonary hypertension: a 1-year follow-up study

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease which results from obstruction of the major pulmonary arteries by incompletely resolved or organized pulmonary emboli which have become incorporated into the pulmonary artery wall, eventually causing an increase in pulmonary vascular resistances. Pulmonary endarterectomy (PEA) is the treatment of choice. Careful pre- and post-operative management is essential for a successful outcome following PEA. In 1994, we started in Pavia a program in which members of a multidisciplinary team work in close interaction with the aim of increase experience in the challenging problems these patients present in the evaluative, surgical, and post-operative phases of their care. So far, 134 PEAs have been performed. Preoperatively, New York Heart Association (NYHA) class distribution was respectively 3-II, 56-III, and 75-IV; mean pulmonary artery pressure and pulmonary vascular resistances were 47 ± 13 mmHg and 1149 ± 535 dynes/sec/cm−5 respectively. The overall operative mortality has been 9.7% (in 2005 mortality rate was 4.5%). At present, 92% of the PEA patients are actively participating in the follow-up study. Follow-up visits are at 3 months after PEA, yearly for the following 5 years, and then at 7, 10, and 15 years postoperatively. Both early and late survivals were excellent. Survival rate at 3 months, 1 year, and 3 years were respectively of 89.5±2.7%, 87.3±3.0%, and 82.7±3.6%. Survival rates had not changed at 5, 7, and 10 years postoperative. Three months after PEA, 29 (58%) subjects were within NYHA class I, 18 (36%) in class II, and 3 (6%) in class III. At 1-year follow-up, 40 (80%) patients were within NYHA class I, 10 (20%) in class II. A statistically significant difference exists not only between the preoperative and the postoperative data (p <0.0001), but also between the functional status at 3 months and the other two postoperative controls (p <0.001). Table summarizes the results of hemodynamic tests collected at three months, one year and three years on the first 35 patients who completed the follow-up program. Hemodynamic data from 35 patients participating to the Pavia Pulmonary Endarterectomy Program with complete 3-year follow-up. CVP mPAP CO CI PVR PVRI CVP (mmHg) central venous pressure; mPAP (mmHg) mean pulmonary artery pressure; CO (L/min) cardiac output; CI (L/min/m2) cardiac index; PVR (dynes/sec/cm-5) pulmonary vascular resistances; PVRI (dynes/sec/cm-5/m2) pulmonary vascular resistances index; RV-EF (%) right ventricle ejection fraction. RV-EF A: Before-PEA 7±6 48±12 3.3±0.9 1.8±0.5 1125±412 2027±731 15±8 B:Before discharge 5±4 25±10 5.2±1.1 2.9±0.5 289±142 505±234 32±8 C: 3 months 2±2 24±11 5.1±1.4 2.8±0.6 231±198 542±271 32±7 D: 1 year 1±2 23±12 5.0±1.1 2.7±0.6 290±191 531±343 35±8 E: 3 years 2±2 24±12 4.9±1.1 2.6±0.5 317±226 579±393 34±8 p value A vs. B: nsA vs. C, D, and E: <0.0001B vs. C, D and E: <0.05 A vs. B, C, D and E: <0.0001 A vs. B, C, D and E: <0.0001 A vs. B, C, D and E: <0.0001 A vs. B, C, D and E: <0.0001 A vs. B, C, D and E: <0.0001 A vs. B, C, D and E:

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Comparison of 2-years follow-up of optimal medical therapy versus balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension

European Heart Journal ◽

10.1093/eurheartj/ehab724.1915 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

Author(s):

A R Pereira ◽

R Cale ◽

F Ferreira ◽

S Alegria ◽

S Sebaiti ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Functional Capacity ◽

Oxygen Therapy ◽

Elevated Serum ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Medium Term ◽

Balloon Pulmonary Angioplasty ◽

Thromboembolic Pulmonary Hypertension

Abstract Introduction Balloon pulmonary angioplasty (BPA) has emerged as a therapeutic option for chronic thromboembolic pulmonary hypertension (CTEPH) considered ineligible for pulmonary endarterectomy (PEA). The initial publications showed very good short-term outcomes for the technique, but there are limited data regarding medium-term outcomes and its comparison with optimal medical treatment (OMT). Objectives To evaluate and compare the medium-term outcomes of OMT versus (vs) BPA in inoperable CTEPH. Methods Retrospective study of consecutive patients (pts) with CTEPH followed in a referral centre for Pulmonary Hypertension. Selected those pts considered ineligible for PEA and with at least 2 years of follow-up. Comparison between two treatment strategies: OMT alone [maximum tolerated doses of pulmonary vasodilator drugs (PVD), as indicated] vs BPA (pts who completed the program with or without OMT). Endpoint was a composite of all-cause death and unplanned right heart failure admission at 2-year. Results From 62 pts, 19 pts were included (11 pts were excluded due to recent diagnosis; 32 were submitted to EAP): mean age 65.0±15.3 years, 89.5% female. At diagnosis, all pts had functional capacity limitation and elevated serum NTproBNP levels (median value 1255.0 pg/mL). Mean pulmonary arterial pressure (mPAP) was 46.2±9.3 mmHg and pulmonary vascular resistance (PVR) 15.3±8.3 Wood units (WU). Concerning treatment, 12 pts (63.2%) underwent OMT alone. These pts had higher NTproBNP levels (2670.0 vs 538.0 pg/mL, p<0.01) and PVR values (19.7±7.6 vs 9.7±5.4 WU, p=0.01) and lower CI (1.6±0.3 vs 2.4±0.5 L/min/m2, p<0.01), at baseline; the remaining basal features didn't differ among groups (Fig.A). At 2-year follow-up, pts submitted to BPA were under PVD in 71.4% of cases with a mean of 1±0.8 drugs per patient and no difference compared to OMT group (83.3%, 1.7±0.9 drugs per patient), although oxygen therapy was higher in medical group (50% vs 0%, p=0.04). A significant overall improvement was observed in BPA group (Table – A): all pts were in functional class I (p<0.01), no one had right ventricular dysfunction (p<0.01) and mPAP decreased to 25.1±6.7 mmHg (p=0.01) and RVP to 2.9±0.8 WU (p=0.01). Inversely, no change was observed in pts under OMT alone (p>0.05 in all, Table – A). Endpoint rate was 31.6% with all adverse events occurring in the OMT group (50% vs 0%, p=0.04). After adjustment by Cox regression, no difference in baseline or follow-up features besides treatment influenced the outcome. Kaplan-Meier analysis (Graphic – B) confirmed significant benefit of BPA in 2-year outcome occurrence (long rank 4.6, p=0.03). Conclusions BPA strategy seems to improve medium-term functional capacity, right ventricular function and haemodynamics and decrease oxygen therapy dependence in inoperable CTEPH. Pts under OMT alone have a poor prognosis. These data encourage the development and implementation of the technique for inoperable CTEPH. FUNDunding Acknowledgement Type of funding sources: None.

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P2772The rule-out criteria for chronic thromboembolic pulmonary hypertension can identify patients without haemodynamic abnormalities and functional limitation 3 and 12 months after acute PE

European Heart Journal ◽

10.1093/eurheartj/ehz748.1089 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Barco ◽

A Mavromanoli ◽

F A Klok ◽

S V Konstantinides

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Hypertension ◽

High Probability ◽

Acute Pulmonary Embolism ◽

Functional Limitation ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Thromboembolic Pulmonary Hypertension ◽

Acute Pe ◽

Rule Out

Abstract Background Up to one-third of patients report persisting hemodynamic abnormalities and functional limitation over long-term follow-up after acute pulmonary embolism (PE). Purpose We tested whether a validated algorithm designed to rule-out chronic thromboembolic pulmonary hypertension (CTEPH) after acute PE can be used for identifying patients at lower risk of presenting with persisting symptoms and echocardiographic abnormalities. Methods The multicentre Follow-up of Acute Pulmonary Embolism (FOCUS) cohort study prospectively enrolled 1,100 consecutive patients diagnosed with acute symptomatic PE; two-year follow-up is ongoing. We focused on the scheduled visits for 3- and 12-month follow-up. The rule-out criteria are based on: the absence of ECG signs of right ventricular dysfunction and normal NT-proBNP/BNP values. Echocardiographic abnormalities were defined according to the presence of abnormal parameters indicating an intermediate/high probability of pulmonary hypertension as recommended by the 2015 ESC/ERS Society Guidelines on Pulmonary Hypertension. The presence of functional limitation was defined based on a World Health Organization classification grade ≥3, a Borg dyspnoea index ≥4, or a 6-minute walking distance <300 m. Results We included 323 patients (mean age 61 years, 58% men), of whom 255 have meanwhile completed a one-year follow-up. At 3- and 12-month follow-up, 194 (60%) and 155 (61%) of patients exhibited no abnormal echocardiographic findings or natriuretic peptide levels. The percentage of patients with echocardiographic abnormalities was 20.4% and 18.0%, respectively. The negative predictive value of the score for ruling out the combination of functional limitation and intermediate/high probability of pulmonary hypertension as recommended by the 2015 ESC/ERS Guidelines on Pulmonary Hypertension was 0.96 (95% CI 0.92–0.98) at 3 and 0.97 (0.92–0.99) at 12 months. The corresponding positive predictive values were 0.10 (0.06–0.17) and 0.09 (0.05–0.17), respectively. Conclusions The CTEPH rule-out criteria are capable of excluding functional limitation and evidence of (chronic) pulmonary hypertension 3 and 12 months after the diagnosis of acute PE. Acknowledgement/Funding The sponsor (University Medical Center of the Johannes Gutenberg University, Mainz) has obtained grants from Bayer Vital GmbH and Bayer Pharma AG

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Patterns of Follow-Up Testing for Chronic Thromboembolic Pulmonary Hypertension After Acute Pulmonary Embolism

10.1164/ajrccm-conference.2020.201.1_meetingabstracts.a6046 ◽

2020 ◽

Author(s):

M.M. Cirulis ◽

L.M. Brown ◽

S.M. Brown ◽

C.G.G. Elliott ◽

M.W. Dodson

Keyword(s):

Pulmonary Embolism ◽

Pulmonary Hypertension ◽

Acute Pulmonary Embolism ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Thromboembolic Pulmonary Hypertension

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Chronic thromboembolic pulmonary hypertension in Saudi Arabia: preliminary results from the SAUDIPH registry

ERJ Open Research ◽

10.1183/23120541.00218-2019 ◽

2020 ◽

Vol 6 (2) ◽

pp. 00218-2019

Author(s):

Abdullah M. Aldalaan ◽

Sarfraz A. Saleemi ◽

Ihab Weheba ◽

Abeer Abdelsayed ◽

Pekka Hämmäinen ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Disease Severity ◽

Tertiary Care ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

World Health ◽

Cumulative Probability ◽

Probability Of Survival ◽

Right Heart Catheterisation ◽

Thromboembolic Pulmonary Hypertension

BackgroundChronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive vascular disease with poor prognosis if left untreated. This study aims to assess the patient characteristics, treatment approach and clinical and survival outcomes for CTEPH patients enrolled in the Systematic Prospective Follow Up for Better Understanding of Clinical Characteristics of Patients with Pulmonary Hypertension Disease (SAUDIPH) registry.MethodsThis study presents a subanalysis of CTEPH patients enrolled in the SAUDIPH registry. This registry enrolled patients with pulmonary hypertension, established through right heart catheterisation, under clinical management at a specialised tertiary care centre. Patients received standard care during the period of the registry.ResultsAt the time of this analysis, 64 CTEPH patients were enrolled in the registry. Mean age at diagnosis was 39.7 years and there was a female predominance (67.6%). At baseline, most patients were in World Health Organization functional classes III or IV (70.1%). At the last follow-up visit, most patients (63.2%) had undergone endarterectomy, showing significant improvement in disease severity from baseline. Patients who underwent endarterectomy showed numerically higher (p=0.126) probability of survival at 1 year (97.5%) versus those who did not undergo endarterectomy (94.4%).ConclusionPatients were diagnosed at relatively young age, but still showed high disease severity, suggesting delay in diagnosis. Patients who underwent surgical treatment showed substantial improvements in clinical and haemodynamic parameters, while the remaining patients tended to show disease progression. The 96.6% 1-year cumulative probability of survival was high compared to previous studies.

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Balloon pulmonary angioplasty improves right atrial reservoir and conduit functions in chronic thromboembolic pulmonary hypertension

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa064 ◽

2020 ◽

Vol 21 (8) ◽

pp. 855-862 ◽

Cited By ~ 1

Author(s):

Yuzo Yamasaki ◽

Kohtaro Abe ◽

Takeshi Kamitani ◽

Kazuya Hosokawa ◽

Masateru Kawakubo ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Feature Tracking ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Right Atrial ◽

Resonance Imaging ◽

Active Function ◽

Balloon Pulmonary Angioplasty ◽

Thromboembolic Pulmonary Hypertension ◽

Rv Function

Abstract Aims Right atrial (RA) function largely contributes to the maintenance of right ventricular (RV) function. This study investigated the effect of balloon pulmonary angioplasty (BPA) on RA functions in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) using cardiac magnetic resonance imaging (CMRI). Methods and results CMRI and RV catheterization were performed before BPA sessions and at the follow-up periods in 29 CTEPH patients. Reservoir [RA longitudinal strain (RA-LS)], passive conduit [RA early LS rate (LSR)], and active (RA late LSR) phases were assessed by using cine CMRI and a feature-tracking algorithm. The relationships between the changes in RA functions and in brain natriuretic peptide (BNP) were evaluated in both the dilated and non-dilated RA groups. RA-LS (32.4% vs. 42.7%), RA LSR (6.3% vs. 8.3%), and RA early LSR (−2.3% vs. −4.3%) were improved after BPA, whereas no significant change was seen in RA late LSR. The changes in RA peak LS and in RA early LSR were significantly correlated with the changes in BNP (ΔRA-LS: r = −0.63, ΔRA-early LSR: r = 0.65) and pulmonary vascular resistance (PVR) (ΔRA-LS: r = −0.69, ΔRA-early LSR: r = 0.66) in the nondilated RA group. Conclusion The RA reservoir and passive conduit functions were impaired in inoperable CTEPH, whereas RA active function was preserved. BPA markedly reversed these impaired functions. The improvements in RA reservoir and conduit functions were significantly correlated with the changes in BNP levels and PVR in CTEPH patients with normal RA sizes.

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Abstract 15125: Percutaneous Transluminal Pulmonary Angioplasty Improves Hemodynamics and Right Ventricular Function in Patients with Chronic Thromboembolic Pulmonary Hypertension -One Year Follow-up Study

Circulation ◽

10.1161/circ.130.suppl_2.15125 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Masanobu Miura ◽

Koichiro Sugimura ◽

Kotaro Nochioka ◽

Tatsuo Aoki ◽

Shunsuke Tatebe ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Right Ventricular Function ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Pulmonary Hemodynamics ◽

Before And After ◽

Thromboembolic Pulmonary Hypertension ◽

Percutaneous Transluminal ◽

Rv Function

Objectives: Right ventricular function (RV) is an important prognostic indicator of pulmonary hypertension. Recent studies have demonstrated that percutaneous transluminal pulmonary angioplasty (PTPA) improves pulmonary hemodynamics in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). In this study, we examined whether PTPA also improves right ventricular dysfunction in those patients. Methods: We performed a total of 252 PTPA procedures (median 4 procedures per patient) for 56 consecutive patients with inoperable CTEPH, after stabilizing their condition using conventional pulmonary vasodilators. Among them, we enrolled 33 patients who had finished 1-year follow-up after final PTPA in the present study (female 81.8%, median age 60 yrs.). RV function was evaluated by tricuspid annular plane systolic excursion (TAPSE) on echocardiogram (42.4%, n=14) and RV ejection fraction (RVEF) on cardiac magnetic resonance imaging (39.4%, n=13) before and after PTPA. Results: No patient died during the PTPA procedure or during the 1-year follow-up period. Comparisons before and after PTPA showed marked improvement of WHO functional class III/IV (75.7 to 0%, P<0.001), 6-min walking distance (316 to 480 m, P<0.001), and brain natriuretic peptide level (93 to 23 pg/ml, P<0.001) and significant hemodynamic improvements for mean pulmonary artery pressure (42.3±10.7 to 24.4±5.7mmHg, P<0.001), cardiac index (2.2±0.6 to 2.7±0.6 L/min•m2, P<0.001) and pulmonary vascular resistance (786±384 to 265±93 dyn•sec•cm5, P<0.001). Furthermore, RV function was also significantly improved for both TAPSE (18.0±4.0 to 23.4±4.3mm, P<0.001) and RVEF (37.9±11.0 to 52.4±7.1%, P<0.001) (Figure). Conclusions: PTPA improves not only pulmonary hemodynamics but also RV function in patients with inoperable CTEPH.

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Prevalence of Coronary Artery to Pulmonary Artery Collaterals in Patients with Chronic Thromboembolic Pulmonary Hypertension: Retrospective Analysis from a Single Center

The Thoracic and Cardiovascular Surgeon ◽

10.1055/s-0036-1584572 ◽

2016 ◽

Vol 66 (02) ◽

pp. 180-186 ◽

Cited By ~ 1

Author(s):

Bulent Mutlu ◽

Ashok Paudel ◽

Cigdem Ileri ◽

Halil Atas ◽

Bedrettin Yildizeli ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Coronary Artery ◽

Pulmonary Artery ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Right Heart Catheterization ◽

Heart Catheterization ◽

Thromboembolic Pulmonary Hypertension ◽

Study Population ◽

Coronary Angiograms

Background Our aim was to determine the prevalence of coronary artery − pulmonary artery collaterals in patients with chronic thromboembolic pulmonary hypertension (CTEPH) by retrospectively evaluating coronary angiograms of eligible consecutive patients who had undergone pulmonary endarterectomy (PEA). We also aimed to evaluate predictors and potential clinical associates of these collaterals. Methods Coronary angiograms of 83 consecutive CTEPH patients who had undergone coronary angiography before PEA operation between January 1, 2012 and June 1, 2015 were retrospectively evaluated for presence of coronary artery − pulmonary artery collaterals. Medical records of all patients were also retrospectively reviewed for demographic information, cardiovascular risk factors, preoperative right heart catheterization reports, operation reports, and follow-up data. Data of CTEPH patients with coronary artery − pulmonary artery collaterals were compared with data of CTEPH patients without such collaterals. Results There were 15 patients (18.1%) with definite and 4 patients (4.8%) with probable coronary artery − pulmonary artery collaterals among the study population. CTEPH patients with collaterals had higher preoperative pulmonary artery pressures, higher pulmonary vascular resistance (PVR) and lower cardiac index values compared with CTEPH patients without collaterals. However, CTEPH patients with collaterals displayed higher amount of reduction in PVR after PEA compared with patients without collaterals. There were no significant differences between groups regarding incidence of reperfusion injury or mortality. Conclusion Prevalence of coronary artery − pulmonary artery collaterals seems to be increased in our CTEPH patients compared with the general population. The presence of coronary artery − pulmonary artery collaterals is often combined with proximal disease with the possibility of increased reduction of PVR after PEA operation.

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