Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension: a systematic review

Introduction

Pulmonary thromboendarterectomy (PTE) represents the treatment of choice for operative patients suffering chronic thromboembolic pulmonary hypertension (CTEPH), and in recent years, guidelines have expanded surgical treatment to all suitable patients (1,2).

In patients who survive acute pulmonary embolism, the literature suggests 0.1% to 4.0% develop CTEPH. This is characterized by thrombus organization within the pulmonary artery and subsequent vascular remodeling in small unobstructed vessels, resulting in pulmonary hypertension and progressive right heart failure (3-5).

The natural history of CTEPH suggests a poor functional quality of life and high mid-term mortality with progressive worsening pulmonary hemodynamics, cardio-pulmonary failure and death. Medically managed CTEPH has a reported three-year mortality rate of 30% to 60% (6,7). Recent series of PTE, however, suggest that this can be improved, and in-patient mortality may be as low as 4% in large volume centers, with survival rates of 90% at three years (8-10).

PTE is being performed and reported by an increasing number of specialist centers worldwide. The procedure has, however, traditionally been associated with high inpatient mortality and morbidity over many years. There is a paucity of robust clinical trial data in the form of randomized control trials. Previous systematic reviews from the 1980s reported a mortality rate of 22%, but by the time of Rahnavardi’s 2011 review which examined studies published between 1999 and 2010, mortality rates ranged from 1.3% to 24% (11,12). Since this time, the international literature has greatly expanded. Within the last decade, there have been several changes in international guidelines and peri-operative management; additionally, there has been the development of medical therapies available to patients with CTEPH, along with the advent of balloon pulmonary angioplasty (BPA). We performed the present systematic review to objectively assess the safety and efficacy of PTE for CTEPH based on the complete literature.

Methods

Literature search strategy

A systematic review was performed searching PubMed, Scopus, EmBase, Medline and the Cochrane library using the key search terms “pulmonary hypertension”, “hypertension, pulmonary”, “chronic thromboembolic pulmonary hypertension” and “endarterectomy”, “pulmonary endarterectomy” “pulmonary hypertension/surgery”. These were filtered by English language publications reported on adult human subjects. Reference lists of included studies were manually reviewed to screen for further articles.

Any duplicate articles were removed. The titles and abstracts of the remaining articles were reviewed by two independent investigators. To address any inconsistencies, the lists were compared and a third investigator resolved any discrepancies. The PRISMA flow diagram is shown in Figure 1.

Figure 1 PRISMA diagram.

Inclusion criteria

Studies selected for appraisal could be either prospective or retrospective. Randomized control trials and cohort studies with greater than ten patients were included. Case reports and conference abstracts were excluded. The primary outcome of interest related to inpatient mortality. Preliminary reading identified several studies that excluded patients who died from their reported morbidity and haemodynamic results. Therefore studies were screened such that included articles presented data for entire cohorts, not just surviving candidates who often would have experienced less morbidity and had generally more favourable hemodynamic and comorbid profiles pre-operatively.

Where patient cohorts from frequently publishing centers overlapped, the largest cohort was selected for inclusion.

Studies that presented data within defined subgroups of PTE patients were only included if they presented perioperative mortality and further data for the entire PTE cohort. Three independent reviewers assessed studies for inclusion and extracted data using a proforma. Studies were assessed and data extracted for study size, date of publication, center of publication, operative period, patient numbers, duration of follow-up, inpatient mortality, patient age, gender, 1-, 3-, 5-, 10-, 15- and 20-year survival. Post-operative outcomes of interest included stroke, reoperation for bleeding, post-operative mechanical support and reperfusion pulmonary oedema. Data relating to residual pulmonary hypertension, reoperation and reintervention for pulmonary hypertension were also captured. If studies reported predictive factors for mortality and residual pulmonary hypertension, these were also recorded. Haemodynamic data regarding pre- and post-operative mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), cardiac output (CO), cardiac index (CI), and patients’ six-minute walk distance (6MWD), New York Heart Association (NYHA) class or World Health Organization (WHO) functional class were also captured.

Analysis

The pooled mortality was assessed by meta-analysis of proportions or means using a random effects model. The relationship between mortality rate and center volume was analyzed utilizing a DerSimonian-Laird random effects bivariate meta-regression model to account for differing center/surgeon experiences and different operative and management protocols across the included studies. Pooled data are presented with 95% confidence intervals (CI) for outcome data. Analysis was performed in STATA/IC 15.1 (13). A P value <0.05 was considered statistically significant.

Publication bias was assessed via an Egger test and funnel plot.

Many morbidity outcomes were heterogeneously/inconsistently reported between studies and were therefore not suitable for meta-analysis; these are reported descriptively.

Study quality was assessed based upon the National Heart, Lung, and Blood Institute (NHLBI) Study Quality Assessment Tool (14). The NHLBI tool assesses whether included studies reported a clear study question with clear objectives, if the cohort was clearly and fully described, if cases were consecutive, if the subjects were comparable, if the intervention was clearly described, if the length of follow-up was adequate, if there was appropriate use of statistical methods and if results were appropriately described.

Results

Literature search

The literature search returned 5,717 publications; 1,164 duplicates were removed. After reviewing the titles and abstracts of these publications, 135 potentially relevant articles were included for full-text review. Following full-text review and removal of overlapping cohorts, sixty-one papers were included for data extraction (Table 1). These studies included six national or international databases and fifty-five single-center studies with a cumulative 9,763 patients from individual reporting institutions. Study population sizes ranged from fifteen to 1,500 patients. Papers were published between 1996 and 2021, with operations being performed between 1970 and 2019. Mortality was reported in all series. Eighteen studies reported one-year survival, four reported ten-year survival. Thirty-three reported morbidity outcomes. Thirty-two reported pre- and post-operative haemodynamics.

Quality of evidence

All studies were assessed for quality based on the NHLBI study quality assessment tool, and all scored between six and nine out of nine (Table 1). There was one randomized control trial included. Twelve included studies were prospective in nature. Other studies were either retrospective or not specified. Very few papers explicitly cited selection criteria for acceptance or exclusion from PTE in CTEPH. Two included studies were from multinational registries. Four included studies were from national registries. These studies are likely to overlap with several of the single center studies.

Search results were assessed for publication bias using the Egger test, which suggested minimal publication bias (P=0.53) (Figure 2).

Figure 2 Funnel plot of studies. Assessment of bias, Egger test (P=0.53).

Mortality

Inpatient mortality ranged from 0.8% to 24.4% across the sixty-one studies as shown in Table 1. Overall mortality via the meta-analysis of proportions was 8.4% (95% CI: 7.2–9.6%). I²=81.1% suggesting considerable heterogeneity of included studies. Mortality by center was inversely associated with the reported volume of cases (P<0.01).

Twenty studies reported factors linked to mortality (Table 1). The most frequently noted were extremely raised PVR pre-operatively, although cut-offs varied between 800–1,100 Dynes (10,16,21,22). Patients with extremely raised PVR, however, had the greatest overall decrease in PVR post-operatively (22). Additionally, poorer functional status, assessed by either 6MWD or NYHA class was associated with increased peri-operative mortality (16,22).

Mid-to-long-term survival

One-year survival was reported in eighteen of the included studies and ranged from 72% to 95.1%, with a median of 91.2% (Table S1). At three years, survival ranged from 67% to 92.5%. Within the European and Chinese registries, three-year survival was 89% (6,17). At five years, survival was 50% to 89.2% as reported across fourteen studies; nine of these studies reported survival of >80% (6,8,10,17,19,22-27,29,35,40,43,44,53,64,66). Previous systematic reviews only included two studies reporting 10- to 15-year survival (12,28,43). The current systematic review included nine studies reporting ten-year survival, which ranged from 62% to 86.1% with a median of 75% (8,19,22,25-28,43,64). Four studies reported 15-year survival: three reported rates between 55% to 59% and Gan et al. reported fifteen-year survival of 29.6% in those with residual pulmonary hypertension compared to 91% in those without residual hypertension (18,27,28,64). No studies reported twenty-year survival.

Major morbidity

Major morbidity was inconsistently reported between studies and is outlined in Table S2. The analysis included twenty-two studies, and the most frequent complication was reperfusion pulmonary oedema. Rates of reperfusion oedema ranged from 3% to 96%, with a median of 18.8% (15,23,26,28,31-33,36-38,42,44,48,50,53,55-57,61,63,65,71).

Mechanical support [generally extracorporeal membrane oxygenation (ECMO), but in one series including intra-aortic balloon pump] was reported in twenty-two of the included studies. It was required in 0% to 56.3% of patients (median 5.5%), with indications including right ventricular support, failure to wean from cardiopulmonary bypass and failure to oxygenate due to reperfusion pulmonary oedema (9,32-34). In the two largest reporting series it was required in 5.1 and 5.5% of patients (9,38). Survival for patients requiring ECMO ranged from 25% to 57% (25,35,72).

Bleeding was heterogeneously reported with multiple definitions, including a return to theatre for bleeding, various decreases in haemoglobin or transfusion of greater than two units of packed red blood cells. Rates of reported bleeding ranged from 0% to 25% (23,26,29,31,32,36-38,42,48,51,65).

Neurological complications were inconsistently reported, with many studies reporting prolonged sedation or confusion as neurological complications. Proven stroke with residual neurological deficit was generally low (21,26,31,44,48).

Duration of hospitalization

Length of intensive care unit stay was reported in twenty-one studies and ranged from four to 15.6 days. This is greatly dependent on the hospitals’ bed flow and ward capacity/ceilings of care. Total post-operative hospital length of stay ranged from ten to forty-five days, with a median of fifteen days (Table S2) (9,15,22,23,25,32,33,36-39,42,44,48-50,53,55-57,62,65,68,69).

Haemodynamics

Thirty-two studies reported pre- and post-operative haemodynamics (Table S3). All thirty-two noted marked improvement in right heart and pulmonary vascular hemodynamics. Postoperatively, CO and CI also improved significantly. In the largest series, PVR improved from 668.8±474.4 to 254.4±224 Dynes across the cohort, with mPAP improving from 45±15 to 25±13 mmHg (9).

Residual pulmonary hypertension was reported in fifteen of the included studies, rates of which ranged from 8.2% to 44.5% (9,23,24,26,30,31,40,44,45,46,49,55,64,66,71). However, it is worth noting that not all studies used the same definition for residual pulmonary hypertension and that many did not explicitly state a defined threshold for residual pulmonary hypertension. Additionally, during recent years, the definition of pulmonary hypertension as per European guidelines has decreased from an mPAP of 25 to 20 mmHg. Many earlier studies also used 30 mmHg as a threshold for residual pulmonary hypertension or only considered it significant if additional medical therapy was initiated (2,73).

Six studies reported factors associated with residual pulmonary hypertension. Raised pre-operative PVR and distal disease were associated with residual pulmonary hypertension (10,24,45,46,66,71).

Recently, BPA has emerged as an adjunct treatment for patients with residual pulmonary hypertension. Several studies reported on rates of BPA after PTE. These ranged from 2.0% to 22.7% for residual pulmonary hypertension or planned hybrid procedures for surgically inaccessible lesions (19,25,40,41).

Functional status

Functional status was noted to improve in all studies reporting either NYHA, WHO functional status and 6MWD (see Table S3). Pre-operatively, 66.4–100% of patients were reported as being WHO/NYHA class III or IV, but only 0% to 25% remained in these functional classes after PTE (Table S3). There was also a corresponding improvement in 6MWD following PTE. All studies noted an improvement in 6MWD, with the greatest increase being more than 200 m (42). Several studies noted major improvements continuing up to the six to twenty-four month mark post-PTE (43-45,74).

Discussion

The present systematic review incorporates the sixty-one most complete studies from hospitals publishing the outcomes of PTE for CTEPH. Although still a relatively morbid procedure by modern surgical standards, this systematic review suggests that overall mortality in a meta-analysis of proportion was was 8.4% (95% CI: 7.2–9.6%). Furthermore, in experienced centers, this may be less than 5% and five-year survival may be as high as 89.2%. In comparison, the three-year mortality rate for medically managed CTEPH is 30% to 60% (6,7).

In contrast to previous reviews, this systematic review has shown a clear association between center volume and mortality. This corroborates the suggestions of the European Database linking PTE outcomes to unit volume, as units performing less than ten surgeries per year had an average inpatient mortality of 8.8%, whereas those performing eleven to fifty-50 surgeries per year reported a mortality rate of 4.5% and centers performing >50 surgeries per year had a mortality rate of 3.4% (6). Several studies reported decreasing mortality over time as the reporting center’s experience expanded (18-20,75). Even very experienced national referral centers report decreasing mortality in recent cohorts. Amsallem et al. at France’s Marie Lannelongue Hospital reported a thirty-day mortality of 1.9% in their most recent cohort in 2016, compared to 4.0% overall from 2012 to 2016 (20). Similarly, Bonderman et al., reporting the outcomes from the Viennese center, noted a gradual decline in mortality from 27% [1992–1995], to 15% [1996–1999], to 6% [2000–2004], to 5% [2004–2006] (75).

Reporting the results of the Spanish national referral center López Gude et al. noted a distinct learning curve (31). Mortality overall was 5.6% but once the learning curve was overcome, this dropped to 2.6%. The learning curve was felt to encompass the first forty-six cases. However, in a study of almost 500 patients, Miyahara et al. noted decreasing mortality with each 100-patient block (18). It is important to recognize that this learning curve likely not only affects surgeons taking on a new, challenging procedure but the whole multidisciplinary team including anaesthetic, perfusion, intensive care and ward staff as they adapt to looking after patients with a complex interplay of respiratory and right heart pathophysiology.

In addition to centers overcoming the surgical learning curve, there have been ongoing general improvements such as the advent of BPA, and development of medications such as Bosentan and Riociguat mid-way through the 2000s and 2010s (76,77). Over time there has been a clear trend both within individual centers and the overall literature to decreasing mortality; this suggests that these developments along with ongoing refinements in intensive care and surgical technique continue to improve outcomes.

Independent predictors of mortality included increasing pre-operative PVR, age and poorer functional status. Ten-year survival of patients with residual pulmonary hypertension was 67.9%±4.7% compared to 89.0%±2.7% in those without (18). Hosokawa and Gan et al. also noted worsened survival at ten and fifteen years depending if the thrombus location was proximal or distal (28,46). Proximal disease was associated with a 94.6% survival rate, compared to 71.8% for distal disease. At fifteen-years post-PTE, this difference became even more marked as survival for proximal disease was 91% against 29.6% for patients with distal disease (28).

Residual pulmonary hypertension is associated with not only worsening survival but also worsened quality of life. Kamenskaya et al. defined residual pulmonary hypertension as the factor that most affects quality of life after PTE (47). Additionally, those with residual pulmonary hypertension also had a greater incidence of hospitalization, persistent low functional capacity and death (48).

A previous meta-analysis reported that 25% of patients suffered residual pulmonary hypertension (78). However, whilst a worthy endeavour to attempt to quantify this problem, residual pulmonary hypertension is difficult to accurately analyze and quantify. This relates to heterogenous definitions for residual pulmonary hypertension. In recent years the definition has changed within international guidelines, and furthermore there is significant variation in the threshold used between papers, ranging from mPAP 20–30 mmHg or using the initiation of medical therapy as indicative of residual/recurrent pulmonary hypertension. These heterogenous definitions make combining these reported rates unreliable. This systematic review notes that 8.2% to 44.5% (median 20%) of patients had residual pulmonary hypertension (47-49).

Patients with the highest pre-operative PVR were more likely to have residual pulmonary hypertension and had higher rates of peri-operative mortality. However, in several of the largest volume referral centers, including the University of California, San Diego and Royal Papworth, patients were not deemed ineligible for PTE based on the severity of pulmonary hypertension or age alone (1,8,9,15). It has also been suggested that the classification of patients as operable or inoperable is even less relevant in the era of BPA, as patients may benefit from a ‘hybrid’ approach of both PTE and BPA in the course of their disease process in addition to medical therapy (1).

Morbidity was inconsistently described. Although utilization of ECMO and reperfusion oedema were well described over a number of studies, most complications were poorly defined and reported. Renal failure rates were as high as 9.4% but were only reported in a handful of series (23,39). Mediastinitis and deep sternal wound infection rates, associated with deep hypothermic arrest in other forms of cardiac surgery, were reported in up to 6% of patients in international registries, but were not reported in series from individual centers (16). Whilst it is a positive step that three significant national registries published results in 2021, only one of these published morbidity data and pre-and post-operative haemodynamic outcomes (17,38,40). It will become increasingly important that these large-volume, well-supported prospective registries continue to collect and report data for CTEPH and patients undergoing PTE. Currently, there is a dearth of randomized controlled trials pertaining to PTE management. Moving forward, it is important that the existing prospective registries adopt similar definitions for blood loss/blood conservation, renal failure and other major complications so that CTEPH morbidity can be better quantified, reported and optimized.

Limitations

There are a number of important limitations when interpreting the results described in the present study. There was significant heterogeneity for some of the reported outcomes. In particular, these were bleeding, neurological complications, reperfusion pulmonary oedema and residual pulmonary hypertension given the changing definitions. Studies also inconsistently reported loss to follow-up, and some studies reported outcomes with high complication rates in small patient populations. The observational nature of the majority of included studies also presents an inherent source of bias in the present study. Additionally, different reporting centers will have different surgeon experiences, patient populations and selection, and variance in surgical technique.

Conclusions

This systematic review reports the outcomes for studies from international PTE centers in the treatment of CTEPH. These outcomes suggest that PTE for CTEPH can be performed with low morbidity and mortality rates, and whilst these continue to improve over time, outcomes remain linked to center volume. Patients can achieve markedly improved haemodynamic indices, and this is associated with improved mid- and longer-term survival. PTE remains the gold standard treatment for surgically accessible CTEPH.

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: The authors have no conflicts of interest to declare.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Jenkins D, Madani M, Fadel E, et al. Pulmonary endarterectomy in the management of chronic thromboembolic pulmonary hypertension. Eur Respir Rev 2017;26:160111. [Crossref] [PubMed]
2. Galiè N, Humbert M, Vachiery JL, et al. 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: The Joint Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC), International Society for Heart and Lung Transplantation (ISHLT). Eur Respir J 2015;46:903-75. [Crossref] [PubMed]
3. Pengo V, Lensing AW, Prins MH, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004;350:2257-64. [Crossref] [PubMed]
4. D'Armini AM, Zanotti G, Viganò M. Pulmonary endarterectomy: the treatment of choice for chronic thromboembolic pulmonary hypertension. Ital Heart J 2005;6:861-8. [PubMed]
5. Gall H, Hoeper MM, Richter MJ, et al. An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan. Eur Respir Rev 2017;26:160121. [Crossref] [PubMed]
6. Delcroix M, Lang I, Pepke-Zaba J, et al. Long-Term Outcome of Patients With Chronic Thromboembolic Pulmonary Hypertension: Results From an International Prospective Registry. Circulation 2016;133:859-71. [Crossref] [PubMed]
7. Byrnes MJ, Ashaye AO, Iheanacho I, et al. Mortality and Survival in Inoperable or Residual/Recurrent Chronic Thromboembolic Pulmonary Hypertension (CTEPH): A Systematic Literature Review. Value in Health 2013;16:378. [Crossref]
8. Madani MM, Auger WR, Pretorius V, et al. Pulmonary endarterectomy: recent changes in a single institution's experience of more than 2,700 patients. Ann Thorac Surg 2012;94:97-103; discussion 103. [Crossref] [PubMed]
9. Newnham M, Bunclark K, Abraham N, et al. CAMPHOR score: patient-reported outcomes are improved by pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. Eur Respir J 2020;56:1902096. [Crossref] [PubMed]
10. Tromeur C, Jaïs X, Mercier O, et al. Factors predicting outcome after pulmonary endarterectomy. PLoS One 2018;13:e0198198. [Crossref] [PubMed]
11. Chitwood WR Jr, Sabiston DC Jr, Wechsler AS. Surgical treatment of chronic unresolved pulmonary embolism. Clin Chest Med 1984;5:507-36. [Crossref] [PubMed]
12. Rahnavardi M, Yan TD, Cao C, et al. Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension : a systematic review. Ann Thorac Cardiovasc Surg 2011;17:435-45. [Crossref] [PubMed]
13. StataCorp. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC; 2017.
14. National Heart, Lung, and Blood Institute. Study Quality Assessment Tools. Available online: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools. 2019.
15. Fernandes TM, Auger WR, Fedullo PF, et al. Baseline body mass index does not significantly affect outcomes after pulmonary thromboendarterectomy. Ann Thorac Surg 2014;98:1776-81. [Crossref] [PubMed]
16. Mayer E, Dahm M, Hake U, et al. Mid-term results of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Ann Thorac Surg 1996;61:1788-92. [Crossref] [PubMed]
17. Deng L, Quan R, Yang Y, et al. Characteristics and long-term survival of patients with chronic thromboembolic pulmonary hypertension in China. Respirology 2021;26:196-203. [Crossref] [PubMed]
18. Miyahara S, Schröder TA, Wilkens H, et al. Long-term Outcomes After Pulmonary Endarterectomy in 499 Patients Over a 20-Year Period. Ann Thorac Surg 2021;111:1585-92. [Crossref] [PubMed]
19. Miwa H, Tanabe N, Jujo T, et al. Long-Term Outcome of Chronic Thromboembolic Pulmonary Hypertension at a Single Japanese Pulmonary Endarterectomy Center. Circ J 2018;82:1428-36. [Crossref] [PubMed]
20. Amsallem M, Guihaire J, Arthur Ataam J, et al. Impact of the initiation of balloon pulmonary angioplasty program on referral of patients with chronic thromboembolic pulmonary hypertension to surgery. J Heart Lung Transplant 2018;37:1102-10. [Crossref] [PubMed]
21. Hartz RS, Byrne JG, Levitsky S, et al. Predictors of mortality in pulmonary thromboendarterectomy. Ann Thorac Surg 1996;62:1255-9; discussion 1259-60. [Crossref] [PubMed]
22. Nierlich P, Hold A, Ristl R. Outcome after surgical treatment of chronic thromboembolic pulmonary hypertension: dealing with different patient subsets. A single-centre experience. Eur J Cardiothorac Surg 2016;50:898-906. [Crossref] [PubMed]
23. Coronel ML, Chamorro N, Blanco I, et al. Medical and surgical management for chronic thromboembolic pulmonary hypertension: a single center experience. Arch Bronconeumol 2014;50:521-7. [Crossref] [PubMed]
24. Escribano-Subías P, Del Pozo R, Román-Broto A, et al. Management and outcomes in chronic thromboembolic pulmonary hypertension: From expert centers to a nationwide perspective. Int J Cardiol 2016;203:938-44. [Crossref] [PubMed]
25. Sakurai Y, Takami Y, Amano K, et al. Predictors of Outcomes After Surgery for Chronic Thromboembolic Pulmonary Hypertension. Ann Thorac Surg 2019;108:1154-61. [Crossref] [PubMed]
26. Korsholm K, Andersen A, Mellemkjær S, et al. Results from more than 20years of surgical pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension in Denmark. Eur J Cardiothorac Surg 2017;52:704-9. [Crossref] [PubMed]
27. Kallonen J, Glaser N, Bredin F, et al. Life expectancy after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: a Swedish single-center study. Pulm Circ 2020;10:2045894020918520. [Crossref] [PubMed]
28. Gan HL, Zhang JQ, Bo P, et al. The actuarial survival analysis of the surgical and non-surgical therapy regimen for chronic thromboembolic pulmonary hypertension. J Thromb Thrombolysis 2010;29:25-31. [Crossref] [PubMed]
29. Rubens FD, Bourke M, Hynes M, et al. Surgery for chronic thromboembolic pulmonary hypertension--inclusive experience from a national referral center. Ann Thorac Surg 2007;83:1075-81. [Crossref] [PubMed]
30. Miller WT Jr, Osiason AW, Langlotz CP, et al. Reperfusion edema after thromboendarterectomy: radiographic patterns of disease. J Thorac Imaging 1998;13:178-83. [Crossref] [PubMed]
31. López Gude MJ, Pérez de la Sota E, Pérez Vela JL, et al. Pulmonary endarterectomy outputs in chronic thromboembolic pulmonary hypertension. Med Clin (Barc) 2017;149:1-8. [PubMed]
32. Fragata J, Telles H. Pulmonary thromboendarterectomy in Portugal: Initial experience. Rev Port Cardiol 2020;39:505-12. (Engl Ed). [Crossref] [PubMed]
33. Vanden Eynden F, Bol Alima M, Racape J, et al. Composite indices of upstream pulmonary vascular impedance and capacitance do not help in identifying patients who should undergo pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. Acta Cardiol 2016;71:281-90. [Crossref] [PubMed]
34. Oh SJ, Bok JS, Hwang HY, et al. Clinical outcomes of thromboendarterectomy for chronic thromboembolic pulmonary hypertension: 12-year experience. Korean J Thorac Cardiovasc Surg 2013;46:41-8. [Crossref] [PubMed]
35. Kelava M, Koprivanac M, Smedira N, et al. Extracorporeal Membrane Oxygenation in Pulmonary Endarterectomy Patients. J Cardiothorac Vasc Anesth 2019;33:60-9. [Crossref] [PubMed]
36. Cain MT, Joyce D, Lahr BD, et al. Do Right Heart Hemodynamic Improvements Persist After Pulmonary Thromboendarterectomy? Semin Thorac Cardiovasc Surg 2022;34:80-9. [Crossref] [PubMed]
37. Leung Wai Sang S, Morin JF, et al. Operative and Functional Outcome After Pulmonary Endarterectomy for Advanced Thromboembolic Pulmonary Hypertension. J Card Surg 2016;31:3-8. [Crossref] [PubMed]
38. Hobohm L, Keller K, Münzel T, et al. Time trends of pulmonary endarterectomy in patients with chronic thromboembolic pulmonary hypertension. Pulm Circ 2021;11:20458940211008069. [Crossref] [PubMed]
39. Lankeit M, Krieg V, Hobohm L, et al. Pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant 2017; Epub ahead of print. [Crossref] [PubMed]
40. Martínez-Santos P, Velázquez-Martín MT, Barberá JA, et al. Chronic thromboembolic pulmonary hypertension in Spain: a decade of change. Rev Esp Cardiol (Engl Ed) 2021;74:384-92. [Crossref] [PubMed]
41. Yanaka K, Nakayama K, Shinke T, et al. Sequential Hybrid Therapy With Pulmonary Endarterectomy and Additional Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension. J Am Heart Assoc 2018;7:008838. [Crossref] [PubMed]
42. Gu S, Liu Y, Su PX, et al. Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: preliminary exploration in China. Chin Med J (Engl) 2010;123:979-83. [PubMed]
43. Freed DH, Thomson BM, Tsui SS, et al. Functional and haemodynamic outcome 1 year after pulmonary thromboendarterectomy. Eur J Cardiothorac Surg 2008;34:525-9; discussion 529-30. [Crossref] [PubMed]
44. Matsuda H, Ogino H, Minatoya K, et al. Long-term recovery of exercise ability after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. Ann Thorac Surg 2006;82:1338-43; discussion 1343. [Crossref] [PubMed]
45. van der Plas MN, Surie S, Reesink HJ, et al. Longitudinal follow-up of six-minute walk distance after pulmonary endarterectomy. Ann Thorac Surg 2011;91:1094-9. [Crossref] [PubMed]
46. Hosokawa K, Ishibashi-Ueda H, Kishi T, et al. Histopathological multiple recanalized lesion is critical element of outcome after pulmonary thromboendarterectomy. Int Heart J 2011;52:377-81. [Crossref] [PubMed]
47. Kamenskaya O, Klinkova A, Chernyavskiy A, et al. Long-term health-related quality of life after surgery in patients with chronic thromboembolic pulmonary hypertension. Qual Life Res 2020;29:2111-8. [Crossref] [PubMed]
48. Ghio S, Klersy C, Corsico A, et al. Risk stratification in patients with residual pulmonary hypertension after pulmonary endarterectomy. Int J Cardiol 2021;334:116-22. [Crossref] [PubMed]
49. Sihag S, Le B, Witkin AS, et al. Quantifying the learning curve for pulmonary thromboendarterectomy. J Cardiothorac Surg 2017;12:121. [Crossref] [PubMed]
50. Narayana Iyengar RM, Hegde D, Chattuparambil B, et al. Postoperative management of pulmonary endarterectomy and outcome. Ann Card Anaesth 2010;13:22-7. [Crossref] [PubMed]
51. Mikus PM, Mikus E, Martìn-Suàrez S, et al. Pulmonary endarterectomy: an alternative to circulatory arrest and deep hypothermia: mid-term results. Eur J Cardiothorac Surg 2008;34:159-63. [Crossref] [PubMed]
52. Archibald CJ, Auger WR, Fedullo PF, et al. Long-term outcome after pulmonary thromboendarterectomy. Am J Respir Crit Care Med 1999;160:523-8. [Crossref] [PubMed]
53. Chen YJ, Ho CT, Tsai FC, et al. Outcomes of Pulmonary Endarterectomy for Chronic Thromboembolic Pulmonary Hypertension at a Single Center in Taiwan. Acta Cardiol Sin 2019;35:153-64. [PubMed]
54. Ji B, Liu J, Wu Y, et al. Perfusion techniques for pulmonary thromboendarterectomy under deep hypothermia circulatory arrest: a case series. J Extra Corpor Technol 2006;38:302-6. [PubMed]
55. Yan S, Lou S, Zhu J, et al. Perfusion strategy and mid-term results of 58 consecutive pulmonary endarterectomy. Perfusion 2019;34:475-81. [Crossref] [PubMed]
56. Hagl C, Khaladj N, Peters T, et al. Technical advances of pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Eur J Cardiothorac Surg 2003;23:776-81; discussion 781. [Crossref] [PubMed]
57. Macchiarini P, Kamiya H, Hagl C, et al. Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: is deep hypothermia required? Eur J Cardiothorac Surg 2006;30:237-41; discussion 241-3. [Crossref] [PubMed]
58. Türer Cabbar A, Değertekin MM, Şimşek MA, et al. Evaluation of Asymmetric Dimethylarginine Levels in Patients With Chronic Thromboembolic Pulmonary Hypertension Undergoing Pulmonary Endarterectomy. Heart Lung Circ 2022;31:110-8. [Crossref] [PubMed]
59. Yanartas M, Kalkan ME, Arslan A, et al. Neutrophil/Lymphocyte Ratio Can Predict Postoperative Mortality in Patients with Chronic Thromboembolic Pulmonary Hypertension. Ann Thorac Cardiovasc Surg 2015;21:229-35. [Crossref] [PubMed]
60. Puis L, Vandezande E, Vercaemst L, et al. Pulmonary thromboendarterectomy for chronic thromboembolic pulmonary hypertension. Perfusion 2005;20:101-8. [Crossref] [PubMed]
61. Dartevelle P, Fadel E, Chapelier A, et al. Angioscopic video-assisted pulmonary endarterectomy for post-embolic pulmonary hypertension. Eur J Cardiothorac Surg 1999;16:38-43. [Crossref] [PubMed]
62. Gilbert TB, Gaine SP, Rubin LJ, et al. Short-term outcome and predictors of adverse events following pulmonary thromboendarterectomy. World J Surg 1998;22:1029-32; discussion 1033. [Crossref] [PubMed]
63. Raza F, Vaidya A, Lacharite-Roberge AS, et al. Initial clinical and hemodynamic results of a regional pulmonary thromboendarterectomy program. J Cardiovasc Surg (Torino) 2018;59:428-37. [Crossref] [PubMed]
64. Kim SH, Lee JW, Ahn JM, et al. Long-term outcomes of surgery for chronic thromboembolic pulmonary hypertension compared with medical therapy at a single Korean center. Korean J Intern Med 2017;32:855-64. [Crossref] [PubMed]
65. Schölzel B, Snijder R, Morshuis W, et al. Clinical worsening after pulmonary endarterectomy in chronic thromboembolic pulmonary hypertension. Neth Heart J 2011;19:498-503. [Crossref] [PubMed]
66. Segel MJ, Kogan A, Preissman S, et al. Pulmonary Endarterectomy Surgery for Chronic Thromboembolic Pulmonary Hypertension: A Small-Volume National Referral Center Experience. Isr Med Assoc J 2019;21:528-31. [PubMed]
67. Balki I, de Perrot M, Bavaghar-Zaeimi F, et al. Clinical Implications of Body Composition and Exercise Capacity Following Pulmonary Endarterectomy. Ann Thorac Surg 2022;113:444-51. [Crossref] [PubMed]
68. Cruz-Suarez GA, Castro-Perez JA, Echavarria-Vasquez JD, et al. Echeverri-Saldarriaga and F. Ariza. Pulmonary endarterectomy in a Colombian cardiovascular center: Experience and main outcomes. Rev Colomb Anestesiol 2018;46:98-102. [Crossref]
69. Dyk W, Szpakowski E, Biederman A, et al. Deep hypothermic circulatory arrest during pulmonary thrombendarterectomy in patients with chronic thrombembolic pulmonary hypertension. Polski Przeglad Chirurgiczny 2007;79:1037-45. [Crossref]
70. Siennicka A, Darocha S, Banaszkiewicz M, et al. Treatment of chronic thromboembolic pulmonary hypertension in a multidisciplinary team. Ther Adv Respir Dis 2019;13:1753466619891529. [Crossref] [PubMed]
71. Mayer E, Jenkins D, Lindner J, 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. [Crossref] [PubMed]
72. Sugiyama K, Suzuki S, Fujiyoshi T, et al. Extracorporeal membrane oxygenation after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension. J Card Surg 2019;34:428-34. [Crossref] [PubMed]
73. Simonneau G, Souz R, editors. PH Haemodynamic definitions and clinical classifications and characteristics of specific PAH subgroups. 6th World Symposium on pulmonary hypertension, Nice, France; February 2018.
74. Cannon JE, Su L, Kiely DG, 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. [Crossref] [PubMed]
75. Bonderman D, Skoro-Sajer N, Jakowitsch J, et al. Predictors of outcome in chronic thromboembolic pulmonary hypertension. Circulation 2007;115:2153-8. [Crossref] [PubMed]
76. Jaïs X, D'Armini AM, Jansa P, et al. Bosentan for treatment of inoperable chronic thromboembolic pulmonary hypertension: BENEFiT (Bosentan Effects in iNopErable Forms of chronIc Thromboembolic pulmonary hypertension), a randomized, placebo-controlled trial. J Am Coll Cardiol 2008;52:2127-34. [Crossref] [PubMed]
77. Ghofrani HA, D'Armini AM, Grimminger F, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013;369:319-29. [Crossref] [PubMed]
78. Hsieh WC, Jansa P, Huang WC, et al. Residual pulmonary hypertension after pulmonary endarterectomy: A meta-analysis. J Thorac Cardiovasc Surg 2018;156:1275-87. [Crossref] [PubMed]