• Users Online: 209
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 10  |  Issue : 2  |  Page : 29-36

The preliminary diagnostic and therapeutic outcomes of chronic thromboembolic pulmonary hypertension registry rajaie cardiovascular medical and research center

1 Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
2 Cardiovascular Intervention Research Center, Rajaie Cardiovascular, Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran
3 Shariati Hospital, Mashhad University of Medical Sciences, Mashhad, Iran
4 Cardiovascular Disease Research Center, Heshmat Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
5 Cardio-Oncology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

Date of Submission26-Jan-2021
Date of Decision13-Feb-2021
Date of Acceptance25-Mar-2021
Date of Web Publication29-Jul-2021

Correspondence Address:
Dr. Samira Arami
Dr. Heshmat Hospital, 15 Khordad Street, Mosalla Square, Rasht
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/rcm.rcm_6_21

Get Permissions


Introduction: We herein present the preliminary results of our center's chronic thromboembolic pulmonary hypertension (CTEPH) registry of the tertiary outcomes of patients diagnosed with CTEPH and treated with pulmonary endarterectomy (PEA), balloon pulmonary angioplasty (BPA), or medical treatment. Methods: The present retrospective cross-sectional study was conducted on patients who received treatment for CTEPH in Rajaie Cardiovascular Medical and Research Center over the past four years, from 2016 to 2020. The data were obtained from routine hospital admission and outpatient visit records. The patients were divided into PEA, BPA, and medical treatment groups, and the outcomes and complications of the procedures were reported. Results: Twenty-eight patients, at a median age of 40 (33–59) years were included in our study and were followed for approximately 20.0 (16.2–23.7) months. PEA was performed on 13 (46%) patients, BPA on 10 (35%), and medical therapy only on 5 (17%). Death occurred in 4 (30%) patients after surgery, and 10 (77%) had a surgical complication. There were no deaths or recorded complications in the other two groups, but the rates of postprocedural pulmonary hypertension (30% vs. 91%; P = 0.006) and rehospitalization (7% vs. 73%; P < 0.001) were significantly lower in the operated patients. The 1-year survival rate among the entire study population was 85.7%. Conclusions: The possibility of CTEPH incidence, especially in high-risk patients with dyspnea, should always be borne in mind given its large morbidity and mortality rate and its chances of curability with early diagnosis and proper treatment.

Keywords: Balloon pulmonary angioplasty, chronic thromboembolic pulmonary hypertension, pulmonary emboli, pulmonary endartherectomy, pulmonary hypertension

How to cite this article:
Taghavi S, Sadeghipour P, Amini S, Arami S, Naderi N, Amin A, Pouraliakbar H, Alizadehasl A, Shafe O, Moosavi J, Ghavidel A, Mohebbi B, Totonchi Z, Azarfarin R, Sadeghi H, Mirdamadi M, Malek H, Rezaei-Kalantari K. The preliminary diagnostic and therapeutic outcomes of chronic thromboembolic pulmonary hypertension registry rajaie cardiovascular medical and research center. Res Cardiovasc Med 2021;10:29-36

How to cite this URL:
Taghavi S, Sadeghipour P, Amini S, Arami S, Naderi N, Amin A, Pouraliakbar H, Alizadehasl A, Shafe O, Moosavi J, Ghavidel A, Mohebbi B, Totonchi Z, Azarfarin R, Sadeghi H, Mirdamadi M, Malek H, Rezaei-Kalantari K. The preliminary diagnostic and therapeutic outcomes of chronic thromboembolic pulmonary hypertension registry rajaie cardiovascular medical and research center. Res Cardiovasc Med [serial online] 2021 [cited 2021 Oct 21];10:29-36. Available from: https://www.rcvmonline.com/text.asp?2021/10/2/29/322586

  Introduction Top

Chronic thromboembolic pulmonary hypertension (CTEPH) is an uncommon on chronic complication of acute pulmonary embolism with a prevalence rate ranging from 0.4% to 9.1%.[1] Approximately 75% of the patients diagnosed with CTEPH have a history of documented acute pulmonary embolism.[2] CTEPH is characterized pathologically by altered vascular remodeling, defective angiogenesis, impaired fibrinolysis, and endothelial dysfunction.[1],[3] Nonresolving fibrothrombotic obstructions in large pulmonary arteries and arteriopathy in small vessels increase pulmonary vascular resistance (PVR), leading to PH and right ventricular (RV) failure.[4],[5] Both lung ventilation/perfusion scanning and pulmonary computed tomography (CT) angiography have excellent efficacy for the detection of CTEPH.[6] Lung ventilation/perfusion scanning remains the preferred initial screening test,[7],[8] while pulmonary CT angiography is widely used for the assessment of operability.[9],[10]

Life-long anticoagulation is the first treatment for all patients.[5] Pulmonary endarterectomy (PEA) is a procedure that can cure these patients and is the first choice for the treatment of patients in the current guidelines.[5],[11] In the International CTEPH registry, about 40% of the patients were considered inoperable due to inaccessible vascular obstructions, pulmonary arterial pressure (PAP) out of proportion to morphological lesions, and significant prohibitive comorbidities.[2] Pulmonary arterial hypertension (PAH)-targeted drug therapy is restricted to inoperable patients or those with resistant or recurrent pulmonary hypertension after surgery.[7] The 3-year survival was about 90% in surgical and 70% in medical groups in registries.[5] Bridging medical therapy before PEA may improve hemodynamics before surgery but does not affect postoperative outcomes.[12]

Balloon pulmonary angioplasty (BPA) is a new promising therapy for inoperable patients.[7] BPA should be performed in specialized centers only for symptomatic patients with CTEPH ineligible for PEA due to distal chronic thromboembolism or persistent/recurrent PH after surgery.[5] BPA complications should be defined and uniformly reported.[5]

Here, we present the findings of the study carried out on the patients diagnosed with CTEPH in our center and treated with PEA, BPA, or medical treatment and also discuss the positive outcomes and complications in each group.

  Methods Top

The present study is a preliminary report of the CTEPH Registry of Rajaie Cardiovascular Medical and Research Center on patients managed with a diagnosis of CTEPH over the past four years. RHC (Rajaei Heart Center) is the third largest cardiovascular center in Iran. Our initial experiences with BPA, underscoring the significance of appropriate infrastructure and teamwork, led to the establishment of the RHC-CTEPH Registry. Our CTEPH team is comprised of heart failure specialists, pulmonologists, cardiac surgeons, radiologists, nuclear medicine specialists, and interventional cardiologists. In keeping with the registry's guidelines, all patients with imaging modalities suggestive of CTEPH underwent right heart catheterization to prove PH, and all patients diagnosed with CTEPH are referred to the CTEPH team for a multidisciplinary recommendation.

The inclusion criteria for the present study consisted of a minimum age of 18 years and PH confirmed by right heart catheterization demonstrating a mean PAP of 25 mm Hg or greater and a pulmonary capillary wedge pressure of 15 mm Hg or less (or >15 mm Hg if justified). Anatomic features and the extension of the disease were identified by CT scanning or pulmonary angiography.

Data collection

Data were obtained from the study population's hospital admission and outpatient visit records collected as routine assessments of patients with CTEPH in the clinical practice, including demographics, clinical signs and symptoms, medical history, functional status, diagnosis, the risk factors of venous thromboembolism and CTEPH, comorbidities, pulmonary function tests, echocardiography, CT angiography, hemodynamics in right heart catheterization, treatment procedures, type of therapy, outcomes, and the complications of the procedures.

Treatment groups

The study population was divided into three groups: PEA, BPA, and medical treatment. Medical therapy was administered with PAH-targeted drugs such as phosphodiesterase (PDE) inhibitors, prostaglandins, and endothelin inhibitors. Bridging therapy is defined as a period of medical therapy before surgery. The criteria for inoperability comprised pulmonary artery obstructions, imbalances between increased PVR, and the amount of accessible occlusion suggesting microvascular disease, a PVR value of greater than 1500 dyn.s/cm5, comorbidities, and the preferences of the physician and the patient. Postoperative PH is defined as a mean PAP of 25 mm Hg or greater by right heart catheterization or a systolic pulmonary artery pressure (SPAP) of 40 mm Hg or greater by echocardiography at day 2 to 3 after the procedure.

Statistical analysis

The categorical variables were reported as numbers and percentages, whereas the continuous variables were reported as the median with the first and third interquartile ranges. The data were analyzed with the SPSS software, version 21.0 (International Business Machines Corp, Armonk, New York, USA). The continuous variables were compared using the independent sample, t-test, or Mann–Whitney test depending on the normality of distributions, and the categorical variables with the Chi-square test. A 2-tip tailed P < 0.05 was considered significant.

  Results Top

Twenty-eight patients with diagnosed with CTEPH were included in our registry and followed for a median of 20.0 (16.2–23.7) months. The patients' demographic and clinical characteristics, together with diagnostic features, are summarized in [Table 1], [Table 2], [Table 3], [Table 4], respectively.
Table 1: Demographics and clinical data of the patients

Click here to view
Table 2: Frequency of risk factors of chronic thromboembolic pulmonary hypertension

Click here to view
Table 3: Drugs used as medical treatment

Click here to view
Table 4: Diagnostic data and treatment results in each treatment groups

Click here to view

Treatment groups

PEA was performed on 13 (46.4%) patients, BPA on 10 (35.7%), and medical therapy only on 5 (17.8%). Regarding medical therapy, beta-blockers were prescribed for 6 (21.4%) patients, calcium channel blockers for 7 (25.0%), diuretics for 14 (50.0%), and digoxin for 5 (17.8%). The patients were on beta blocker or calcium channel blocker before our admission because of coronary artery disease or hypertension which were stopped anywhere not indicated. All of them used anticoagulants: 22 (78.5%) patients consumed warfarin and 3 (10.7%) used either apixaban or rivaroxaban. Fifteen (53.5%) patients were given PH-specific therapy: seven patients used just PDE5 inhibitors, 4 used a combination of PDE5inhibitors and bosentan, 3 used this combination with intravenous prostaglandin, and 1 patient received bosentan and intravenous prostaglandin. Six (46.1%) patients in the surgery group and 6 (60.0%) others in the BPA group received these drugs before the procedure. The clinical, diagnostic, and therapeutic characteristics of each treatment group are summarized in [Table 4].

Surgical group

Thirteen (46.4%) patients underwent standard PEA. Bridge therapy was used in 6 (46.1%) patients with PH-specific drugs before surgery and 1 patient received intravenous prostaglandin. The median pump time was 215.0 (200.0–280.0) min. Ten (76.9%) patients experienced postoperative complications: 6 (46.1%) patients developed reperfusion edema, 4 (30.7%) patients needed extracorporeal membrane oxygenation (ECMO) due to hemodynamic instability, 3 (23.0%) patients suffered significant bleeding and needed packed cells infusion, 2 (15.3%) patients had hemoptysis, 1 (7.6%) patient developed pneumonia, 1 (7.6%) patient sustained tamponade, 1 (7.6%) patient had acute renal failure, and 1 (7.6%) patient experienced adrenal insufficiency. In addition, 6 (46.1%) patients had severe, 3 (23.0%) had moderate postoperative RV dysfunction, and 3 (23.0%) patients had postoperative PH (SPAP >40 mm Hg) in echocardiography in the intensive care unit (ICU) with a median SPAP of 32.0 (25.0–62.0) mm Hg.

Death occurred in 4 (30.7%) patients: 3 died on the first postoperative day because of complications (in-hospital mortality rate = 23.1%), and 1 patient died 8 months after surgery due to disease progression. All the nonsurviving patients had severe RV dysfunction following surgery, and ECMO was implanted for 2 of them. Two of these nonsurviving patients had reperfusion edema and bleeding, 1 had acute renal failure, and 1 had hemoptysis. The patient who died 8 months after surgery suffered from postprocedural reperfusion edema, pneumonia, and hemoptysis. Recurrent hospitalization after surgery was reported only in the case of the same patient (10%). The mean number of hospitalizations was 2 (1–3) times in this group.

Although none of the preprocedural parameters showed significant differences due to the small number of patients, the nonsurviving patients exhibited a trend toward having higher proBNP levels (5100.1 [4131.5–5100.2] vs. 842.5 [132.4–3000.5] ng/dL; P = 0.167), longer intervals between symptom occurrence and surgery (78.0 [24.0–112.5] vs. 4.0 [1.2–10.5] mon; P = 0.217), longer intervals between acute embolism and CTEPH diagnosis (72.0 [24.0–72.0] vs. 12.0 [2.5–36.0] mon; P = 0.236), and longer cardiocirculatory arrest durations (277.0 [212.0–295.0] vs. 210.0 [200.0–233.0] min; P = 0.242).

The median postoperative SPAP in echocardiography differed significantly between the nonsurviving and surviving patients (70.5 [60.3–70.5] vs. 30.5 [25.4–35.6] mm Hg; P = 0.017).

Balloon pulmonary angioplasty group

Ten (35.7%) patients underwent BPA. The intervention was done in 1 session in 5 (50.0%) patients, 2 sessions in 4 (40.0%), and 6 sessions in 1 (10.0%). Three (30.0%) patients suffered nonmassive hemoptysis, and no death occurred in this group [Table 4].

Medical therapy group

Surgery was not performed in 15 (53.5%) patients because of the patients' refusal or unsuitable anatomies [Table 4]. There were only 5 (17.8%) patients who did not undergo any intervention and just received medical treatment.

Comparison between operated and nonoperated patients

There were no deaths and important complications in the nonoperated group; however, the incidence rates of postprocedural PH (23.1% vs. 91%; P = 0.006) and rehospitalization (10.0% vs. 73.3% [0 vs. 2 times]; P < 0.001) were significantly lower in the operated patients.


The 1-year survival rate among the entire study population was 85.7%. The rate was 100% in the BPA and medical treatment groups. The rate of in-hospital mortality after surgery was 23.1%. Further, the rate of 1-year survival following hospital discharge was 90%.

  Discussion Top

This is the first report on the RHC-CTEPH registry, which encompassed 28 patients with a confirmed diagnosis of CTEPH followed for 20.0 (16.2–23.7) months.

Risk factors and patients characterizations

The risk factors of CTEPH are different from those of acute pulmonary embolism, and the prevalence rates of pulmonary embolism vary in different studies: between 40% and 60% in previous studies and from 15% to 33% in Japanese reports.[2] In our study, the frequency of acute embolism and deep-vein thrombosis was 75% and 50%, correspondingly, which chimes in with the latest international registry, reporting a 75% rate for venous thromboembolism.[2] Also concordant with large investigations, our findings showed a 12-month period between the last acute embolism and CTEPH diagnosis.[2]

Comorbidities in our patients included diabetes, chronic kidney disease, chronic obstructive pulmonary disease, obesity, coronary artery disease, hypothyroid, history of hospitalization, and bone fracture. The most frequent risk factor was hypercoagulopathy (43%), which is in agreement with a registry introduced by Delcroix et al.,[4] who reported a rate of 53% for thrombophilia, mostly antiphospholipid A syndrome. Although our sample volume was small, 18% of the study population had antiphospholipid syndrome; other disorders included protein C or S deficiency, systemic lupus, scleroderma, splenectomy, and hormonal disturbances, which have also been reported in previous studies.[2],[4]

Our patients were admitted mostly in New York Heart Association (NYHA) Functional Class (FC) II or III with a median of a 360-m walk in the 6-min walk test, and we had no patient in FC IV at the beginning of the disease, which is different from the international registry, in which the majority of the patients were in NYHAFC III or IV with a median of a 329-m walk in the 6-min walk test.[2],[4] It is possible that our patients mentioned earlier, those in NYHAFC IV had more comorbidities, or other reasons for dyspnea deviated the diagnosis. The median time between symptom onset and diagnosis in our investigation was 2.5 months, which is significantly shorter than the time in the international registry (14 mon) and other older studies (several years).[2] This duration was not significantly different between the treatment groups; however, it had a trend toward being longer in the operated patients.

Diagnostic test results

The screening test for most of our patients was lung perfusion scanning, the result of which was abnormal in the whole study population. With its high negative predictive value, lung perfusion scanning is deemed the first-choice screening test to rule out CTEPH.[2] We conducted CT angiography to establish the diagnosis and delineate the anatomy of the vessels. Proximal lesions were detected in 75% of the patients, and the nonoperated group had a significantly higher frequency of distal involvement, which prompted our CTEPH team physicians to opt for a therapeutic modality other than surgery.[2],[4],[5]

All of our patients had high SPAP and RV dysfunction in echocardiography. In addition, most of them had significant right atrial and RV enlargement with about 20% pericardial effusion, a marker of RV failure. These values were not significantly different between the operated and nonoperated groups.

Right heart catheterization showed significantly high mean PAP and PVR and low cardiac output and cardiac index, which closely resemble the values reported in large studies.[2] These amounts were not statistically significantly different between our treatment groups, as was the case in the large international registry.[2]

Pulmonary hypertension medical treatment

Anticoagulants, the most acceptable drugs for patients suffering from CTEPH, should be continued lifelong.[5] We administered anticoagulants to our entire study population. Notably, the only PH-specific drug that has been approved for CTEPH therapy is riociguat,[11],[13] which is unavailable in our country.

In our study, 54% of the patients received at least 1type of PAH-targeted drug: PDE5 inhibitors, bosentan, or intravenous prostanoids. These drugs have been used in multiple studies in patients considered inoperable due to concerns over inaccessible vascular obstructions, PAP out of proportion to morphological lesions, and significant prohibitive comorbidities.[2] Moreover, these drugs have effected varying degrees of improvement in patients with persistent PH and high PVR after surgery.[11],[14],[15],[16] We utilized these drugs in 46% of our operated patients as a bridge to surgery. Be that as it may, this method is controversial insofar as it appears to delay timely surgical referrals and therefore definitive treatments.[5]

Mayer et al.[16] posited that meticulously selected high-risk patients might benefit from PAH-specific therapies to optimize pulmonary hemodynamics before surgery. They also suggested that in patients whose surgery was delayed owing to limited medical resources, pretreatment might prevent clinical deterioration. Several open-label studies have suggested beneficial effects for patients with severe CTEPH waiting for surgery and receiving treatment with prostacyclin or bosentan.[2] However, medical treatment has the risk to make unnecessary delays to a potentially curative surgical intervention.[16]

In two large cohorts, 28% and up to 37% of the patients were on some form of PH-targeted drug (s) at the time of surgical referral, which doubled the delay between diagnosis and surgery without demonstrable clinical benefits.[2],[17] In the international registry, pretreatment even independently predicted a worse outcome.[4] There are currently ongoing studies on patients suffering from CTEPH with high PVR to compare preoperative treatment between riociguat and aplacebo.[5] In our BPA group, 60% of the patients received these drugs as a bridge to BPA. This method, albeit a common practice, is still under investigation.[5]

Pulmonary endarterectomy outcomes

In our study, PEA was performed in 46% of the patients. The figure is 54% in the international registry.[2] No operability was due to the inaccessibility of occlusions, imbalances between increased PVR and the number of accessible occlusions, comorbidities, the surgeons' preferences, or the patients' refusal. Although we could not show significant differences due to the small number of our patients, the surgical group exhibited a trend toward being younger, having higher proBNP levels, having lower cardiac outputs, and having longer intervals between symptom onset and CTEPH diagnosis and treatment [Table 4].

In the current investigation, the rate of surgical complications and in-hospital mortality was 76.9% and 23.1%, respectively, which is much higher than the rate in the international registry (49% perioperative complications and 4.7% in-hospital mortality).[2],[16]

In a study by Mayer et al.,[16] perioperative complications were infection, persistent PH, neurologic or bleeding complications, pulmonary reperfusion edema, pericardial effusion, and need for ECMO, which were noted in our patients too.

The in-hospital mortality rates in recent worldwide series ranged from 4.4% to 16%.[2] Mayer et al.[16] argued that their low mortality rate (4.7%) was due to enhanced technical experience, the appropriate selection of surgically eligible patients, and the inclusion of exclusively newly diagnosed patients into the registry.

The important differences vis-à-vis operated patients between our study and the one carried out by Mayer et al.[16] are that they explored newly diagnosed patients, their median time from CTEPH diagnosis to surgery was 78 days, and their median duration of circulatory arrest was 35 minutes, where as our median time from the beginning of the disease to surgery was 240 days and our median pump time was 215 min, which seems to be one of the reasons for our weaker surgery results. According to Mayer et al., the duration of circulatory arrest was a risk factor for developing neurologic complications. They also concluded that PVR and the 6-minute walk test at diagnosis and PVR at the end of the ICU stay were associated with in-hospital and 1-year mortality. Moreover, Mayer et al. stated that time from the last pulmonary embolism to PEA and the initiation of PAH-specific treatment at diagnosis were risk factors for in-hospital mortality. In their study, the mortality rate tended to be higher in patients with no history of pulmonary embolism, worse NYHA FC at diagnosis, and the circulatory arrest duration. Although our small sample size precluded us from establishing significant associations between preoperative factors and mortality, our nonsurviving group had a trend toward having higher proBNP levels, longer intervals between symptom onset and surgery, and longer intervals between pulmonary embolism and CTEPH diagnosis, which might have contributed to delayed treatment, more advanced disease, and worse prognosis. One remarkable technical factor in our surgical reports was the long duration of circulatory arrest, which exhibited a trend toward being longer in the nonsurviving patients. Needless to say, the circulatory arrest duration is one of the factors that are eminently correctable. In their study,[16] the circulatory arrest was only 35 min; some patients did not have any arrest time and others had a maximum cumulative time of 146 min. Modifications to the PEA procedure have been introduced to avoid circulatory arrest; nonetheless, they have not been demonstrated to provide substantial benefits when compared with the traditional technique.[16]

In the study by Mayer et al.,[16] the best operative outcome required a significant early reduction in PVR, to optimally less than 500 dyn.s/cm5, but PVR failed to return to near-normal levels by the end of the ICU stay in 16.7% of the patients. The authors explained these results by positing that those patients had more compromised hemodynamics and exercise capacity at diagnosis with more vasculopathy, which prevented them from deriving full benefits from surgery.[2] None of our patients had right heart catheterization after surgery, but our nonsurviving group had significantly higher SPAP in the postprocedural echocardiography in the ICU, which could be a maker of higher PVR.

Previous studies have shown that most of the improvements in hemodynamics are achieved immediately after PEA, as an immediate result of the relief of central mechanical obstruction, accompanied by improvements in clinical symptoms, improvements in the 6-minute walk test results, and the return to NYHA FCI or II during the first year after surgery.[2],[16] Unfortunately, we did not have the hemodynamic and functional data of our survived patients; nevertheless, the small number of re-hospitalized cases after surgery indicates that they might be in good condition.

An expert surgical center is one that meets three criteria: Surgical mortality rates of below 5%, surgical volumes of more than 50 PEA procedures per year, and the ability to perform segmental endarterectomy.[18] Our hospital is a referral center, but only 2 to 3 PEA procedures are performed per year, which hints at the substantial number of missed CTEPH diagnoses and the urgent need to gain experience for the attainment of the ideal goal.

Balloon pulmonary angioplasty outcomes

BPA has evolved into an integral component of the CTEPH treatment algorithm since the 2012 reports from Japan[17],[19],[20] showed that it could improve hemodynamics, symptoms, exercise capacity, and RV function, with significantly lower rates of major complications by comparison with previous reports.[21],[22],[23] The complications of BPA appear to be more vascular injury related to the intervention than the capillary leak syndrome described post-PEA.[24] Injury caused by wire perforation or the interruption of the diseased vessel is the most common.[25] Lung injury by wire perforation or balloon over dilatation in the setting of severe PH carries the risk of potentially fatal massive infiltration and hemorrhage, which may require mechanical ventilation or extracorporeal support. Allergic reactions to the contrast material and adverse reactions to conscious sedation and local anesthesia have been reported. Classic reperfusion lung injury is rare with BPA.[5]

We performed BPA in 10 inoperable patients: 5 patients just in 1 session, 4 patients in 2 sessions, and 1 in 6 sessions. We had neither deaths nor intervention-related complications. However, all the patients still had postprocedural PAH, 70% had moderate-to-severe RV dysfunction, and about 80% were still symptomatic and needed at least 1 hospital admission after the procedure. Unfortunately, there were no recorded data regarding the patients' functional classes and hemodynamics in the follow-up, and we still need prospective studies with larger numbers of patients and better follow-ups to observe the outcomes of BPA in our center.

In a study by Mizoguchi et al.,[19] 68 patients underwent BPA in a staged fashion in a total of 4 (2–8) sessions to maximize efficacy and reduce the risk of reperfusion pulmonary injury. The patients' NYHA FC was improved from III to II, and the mean PAP significantly decreased. One patient died because of right heart failure, and 60% developed reperfusion pulmonary injury, with 4 cases requiring mechanical ventilation. Jin et al.[26] performed BPA in 25 patients with significant hemodynamic and functional improvements without any complications. Kataoka et al.[20] investigated 29 patients who underwent BPA and reported 1 death due to wiring perforation and 53% reperfusion edema. BPA did not produce immediate hemodynamic improvements; however, during a 6-month follow-up, hemodynamic parameters, functional classifications, and levels of plasma proBNP significantly improved.

In experienced hands, BPA has emerged as a promising and established treatment for inoperable CTEPH. Reports from expert centers may not be generalizable. It remains a steep learning curve in order to safely, effectively, and consistently perform BPA.[27]

Our postprocedural1-year survival rate was 87.5% in the operated group and 100% in the nonoperated group; nonetheless, the rates of posttreatment PH and the number of rehospitalized cases were significantly lower in the operated patients, although the total number of hospitalized cases was not significantly different between the groups. This finding does not tally with the international registry, with a reported 3-year survival rate of 90% in operated patients and 70% in those not having surgery.[26] The difference might be due to our small number of patients, the worse condition of the operated patients at baseline, and more delays to treatment, especially in the case of the nonsurviving patients. It is worthy of special note that PEA should be offered to all eligible patients with CTEPH.[5]

This article is the first report of outcomes of the different treatment of this uncommon fatal disease in our country and could display weakness' and power of our diagnostic and therapeutic approaches and can lead to more attention not to miss this important diagnosis in high risk patients and selection of the proper therapy by knowledge of the results from this referral Center and it can help researchers for bigger future studies.


This was a single center retrospective study with a limited number of patients and some data about history and diagnostic tests were missing in the hospital files. It is worth planning for a bigger prospective multicenter study for a better evaluation in the future.

  Conclusions Top

CTEPH, albeit not a very common problem, needs attention, at least in high-risk patients given its large morbidity and mortality and its chances of curability with early diagnosis and proper treatment. Surgery is still the first choice, and BPA can be helpful in inoperable patients.

Ethical clearance

This study was approved by the Ethics Committee of Rajaie Cardiovascular Medical and Research Center (RHC), Iran University of Medical Science; all necessary permissions were obtained from the relevant authorities prior to beginning the study. Ethics code number: RHC-95082.

Financial support and sponsorship

This study was financially supported by Rajaei Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran.

Conflicts of interest

There are no conflicts of interest.

  References Top

Lang IM, Pesavento R, Bonderman D, Yuan JX. Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: A current understanding. Eur Respir J 2013;41:462-8.  Back to cited text no. 1
Pepke-Zaba J, Delcroix M, Lang I, Mayer E, Jansa P, Ambroz D, et al. Chronic thromboembolic pulmonary hypertension (CTEPH): Results from an international prospective registry. Circulation 2011;124:1973-81.  Back to cited text no. 2
Dorfmüller P, Günther S, Ghigna MR, Thomas de Montpréville V, Boulate D, Paul JF, et al. Microvascular disease in chronic thromboembolic pulmonary hypertension: A role for pulmonary veins and systemic vasculature. Eur Respir J 2014;44:1275-88.  Back to cited text no. 3
Delcroix M, Lang I, Pepke-Zaba J, Jansa P, D'Armini AM, Snijder R, et al. Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. Circulation 2016;133:859-71.  Back to cited text no. 4
Kim NH, Delcroix M, Jais X, Madani MM, Matsubara H, Mayer E, et al. Chronic thromboembolic pulmonary hypertension, Eur Respir J 2019;53:1801915.  Back to cited text no. 5
He J, Fang W, Lv B, He JG, Xiong CM, Liu ZH, et al. Diagnosis of chronic thromboembolic pulmonary hypertension: Comparison of ventilation/perfusion scanning and multidetector computed tomography pulmonary angiography with pulmonary angiography. Nucl Med Commun 2012;33:459-63.  Back to cited text no. 6
Kim NH, Delcroix M, Jenkins DP, Channick R, Dartevelle P, Jansa P, et al. Chronic thromboembolic pulmonary hypertension. J Am Coll Cardiol 2013;62:D92-9.  Back to cited text no. 7
McLaughlin VV, Langer A, Tan M, Clements PJ, Oudiz RJ, Tapson VF, et al. Contemporary trends in the diagnosis and management of pulmonary arterial hypertension: An initiative to close the care gap. Chest 2013;143:324-32.  Back to cited text no. 8
Ley S, Ley-Zaporozhan J, Pitton MB, Schneider J, Wirth GM, Mayer E, et al. Diagnostic performance of state-of-the-art imaging techniques for morphological assessment of vascular abnormalities in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Eur Radiol 2012;22:607-16.  Back to cited text no. 9
Sugiura T, Tanabe N, Matsuura Y, Shigeta A, Kawata N, Jujo T, et al. Role of 320-slice CT imaging in the diagnostic workup of patients with chronic thromboembolic pulmonary hypertension. Chest 2013;143:1070-7.  Back to cited text no. 10
Ghofrani HA, D'Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013;369:319-29.  Back to cited text no. 11
Reesink HJ, Surie S, Kloek JJ, Tan HL, Tepaske R, Fedullo PF, et al. Bosentan as a bridge to pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J Thorac Cardiovasc Surg 2010;139:85-91.  Back to cited text no. 12
Simonneau G, D'Armini AM, Ghofrani HA, Grimminger F, Jansa P, Kim NH, et al. Predictors of long-term outcomes in patients treated with riociguat for chronic thromboembolic pulmonary hypertension: Data from the CHEST-2 open-label, randomised, long-term extension trial. Lancet Respir Med 2016;4:372-80.  Back to cited text no. 13
Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jaïs X, et al. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): Results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med 2017;5:785-94.  Back to cited text no. 14
Cannon JE, Su L, Kiely DG, Page K, Toshner M, Swietlik E, et al. Dynamic risk stratification of patient long-term outcome after pulmonary endarterectomy: Results from the united kingdom national cohort. Circulation 2016;133:1761-71.  Back to cited text no. 15
Mayer E, Jenkins D, Lindner J, D'Armini A, Kloek J, Meyns B, et al. Surgical management and outcome of patients with chronic thromboembolic pulmonary hypertension: Results from an international prospective registry. J Thorac Cardiovasc Surg 2011;141:702-10.  Back to cited text no. 16
Mizoguchi H, Ogawa A, Munemasa M, Mikouchi H, Ito H, Matsubara H. Refined balloon pulmonary angioplasty for inoperable patients with chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012;5:748-55.  Back to cited text no. 17
Jenkins D, Madani M, Fadel E, D'Armini AM, Mayer E. Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2017;26:160111. https://doi.org/10.1183/16000617.0111-2016.  Back to cited text no. 18
Kataoka M, Inami T, Hayashida K, Shimura N, Ishiguro H, Abe T, et al. Percutaneous transluminal pulmonary angioplasty for the treatment of chronic thromboembolic pulmonary hypertension. Circ Cardiovasc Interv 2012;5:756-62.  Back to cited text no. 19
Sugimura K, Fukumoto Y, Satoh K, Nochioka K, Miura Y, Aoki T, et al. Percutaneous transluminal pulmonary angioplasty markedly improves pulmonary hemodynamics and long-term prognosis in patients with chronic thromboembolic pulmonary hypertension. Circ J 2012;76:485-8.  Back to cited text no. 20
Ogo T. Balloon pulmonary angioplasty for inoperable chronic thromboembolic pulmonary hypertension. Curr Opin Pulm Med 2015;21:425-31.  Back to cited text no. 21
Fukui S, Ogo T, Goto Y, Ueda J, Tsuji A, Sanda Y, et al. Exercise intolerance and ventilatory inefficiency improve early after balloon pulmonary angioplasty in patients with inoperable chronic thromboembolic pulmonary hypertension. Int J Cardiol 2015;180:66-8.  Back to cited text no. 22
Fukui S, Ogo T, Morita Y, Tsuji A, Tateishi E, Ozaki K, et al. Right ventricular reverse remodelling after balloon pulmonary angioplasty. Eur Respir J 2014;43:1394-402.  Back to cited text no. 23
Lang I, Meyer BC, Ogo T, Matsubara H, Kurzyna M, Ghofrani HA, et al. Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2017;26:160119. 160119 [https://doi.org/10.1183/ 16000617.0119-2016].  Back to cited text no. 24
Kawakami T, Ogawa A, Miyaji K, Mizoguchi H, Shimokawahara H, Naito T, et al. Novel angiographic classification of each vascular lesion in chronic thromboembolic pulmonary hypertension based on selective angiogram and results of balloon pulmonary angioplasty. Circ Cardiovasc Interv 2016;9:e003318.  Back to cited text no. 25
Jin Q, Luo Q, Yang T, Zeng Q, Yu X, Yan L, et al. Improved hemodynamics and cardiopulmonary function in patients with inoperable chronic thromboembolic pulmonary hypertension after balloon pulmonary angioplasty. Respir Res 2019;20:250-61.  Back to cited text no. 26
Ogawa A, Matsubara H. Balloon pulmonary angioplasty: A treatment option for inoperable patients with chronic thromboembolic pulmonary hypertension. Front Cardiovasc Med 2015;2:4.  Back to cited text no. 27


  [Table 1], [Table 2], [Table 3], [Table 4]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  In this article
Article Tables

 Article Access Statistics
    PDF Downloaded88    
    Comments [Add]    

Recommend this journal