A multidisciplinary team, made up of pulmonologists, surgeons, cardiologists, anesthetists, radiologists, and intensive medicine specialists studied the viability of surgery. The decision to operate was based on FC, accessibility of thrombotic lesions, hemodynamic status, and comorbidities.

An inferior vena cava filter was placed in all patients before surgery.

The surgical procedure was performed according to the technique described by Jamieson23 and all extracted material was sent for pathological examination. The technique consisted of bilateral PE performed via median sternotomy with extracorporeal circulatory support and periods of intermittent hypothermic circulatory arrest.24

After anesthetic induction, a Swan-Ganz catheter was placed in the pulmonary artery and a transesophageal echocardiogram transducer was introduced. Patients were ventilated mechanically with orotracheal intubation in the operating room and subsequently in the intensive care unit (UCI) for 12–48h. In the immediate post-operative period, patients received treatment with intravenous diuretics, proton pump inhibitors, and antibiotic prophylaxis. They were also anticoagulated with intravenous sodium heparin in the absence of significant bleeding. Until 2009, inhaled NO was used systematically in the immediate post-operative period in all operated patients. Later, it was used only in patients with residual post-operative PH.

Patients classified as inoperable or who refused surgery began MT with calcium antagonists or specific anti-PH drugs (Fig. 1).

Fig. 1.

Flowchart of study patients. PE: pulmonary endarterectomy; PAH: pulmonary arterial hypertension; PH: pulmonary hypertension; mPAP: mean pulmonary arterial pressure; PVR: pulmonary vascular resistance; MT: medical treatment.

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Patients were called for a visit to the dedicated PH clinic in our center after 30 days, 3 months, and then every 3 months after hospital discharge, in the case of patients who underwent PE, or after diagnosis for TM patients.

Pulmonary hemodynamics after PE was reassessed on discharge in 8 patients and in 16 patients between 6 and 24 months after surgery. Follow-up hemodynamic evaluations were not performed systematically in all non-surgical patients. In cases with poor progress after starting MT or if a poor prognosis was determined from diagnostic catheterization (24 patients), hemodynamic testing was repeated 6–24 months later. In all cases, survival, FC, and exercise tolerance (6MWT) at 12 months were determined.

The following data were included in the analysis: demographic data, pre-operative or pre-MT data (FC, distance walked on 6MWT, and hemodynamics), post-operative variables (length of ICU stay in days, hours of mechanical ventilation, and morbidity), and follow-up data (mortality, and the same clinical and hemodynamic data as collected in the pre-operative period).

In order to separate mortality associated with surgery from disease-associated mortality, a conditional survival analysis was performed in patients alive 100 days after PE. In addition, with the aim of evaluating the effect of experience on perioperative mortality, survival in an initial period from 2000 to 2006 and in a second period from 2007 to 2012 were analyzed separately. Continuous variables are presented as mean±standard deviation (SD) or median and interquartile range (IQR), depending on whether distribution was normal or not. Categorical variables are presented as absolute values and percentages (%). Quantitative variables were analyzed using the Student's t-test or the Mann–Whitney U-test, depending on whether distribution was normal or not. Association between categorical variables was analyzed using the Chi-squared test or Fisher's exact test. Survival curves were calculated using the Kaplan–Meier method. Comparison of survival between groups was carried out using the log-rank test.

A P-value <.05 was considered statistically significant. All statistical analyses were performed using SPSS 18.0 software (SPSS Inc., Chicago, IL).

The study population was formed of 80 patients with consecutive diagnoses of CTEPH in the period between January 2000 and July 2012, with minimum follow-up of 6 months (Fig. 1). Thirty-three patients (41.3%) were men, and the mean age was 57±16 years. A total of 74% of patients presented FC III–IV, while 21% had a history of syncope and 37% had signs of right heart failure. At the time of diagnosis, mean distance walked on the 6MWT was 352±123m.

A total of 38% of patients had a history of deep venous thrombosis and 23% showed thrombophilia, lupus anticoagulant being the most common factor (15%).

A total of 36 patients (45%) were considered candidates for PE, of which 32 finally underwent the procedure (PE group) (Fig. 1). In comparison with the group that received only MT, patients in the PE group were younger and predominantly male (Table 1). The proportion of patients with FC III–IV was similar and the PE group achieved greater distances on the 6MWT. Both groups had a similar hemodynamic profile.

Fourteen patients (43.7%) were operated without preconditioning treatment, while 18 (56.3%) underwent presurgical preconditioning to reduce pulmonary vascular resistance (PVR). These treatments included endothelin receptor antagonists (ERAs) (27.8%), phosphodiesterase-5 (PDE-5) inhibitors (22.2%), prostanoids (11.1%), calcium antagonists (11.1%), and combined therapy (27.8%).

During PE, median excorporeal circulation time was 152min (IQR 139–180) and median circulatory arrest time was 24min (IQR 16–36). After intervention, median mechanical ventilation time was 2 days (IQR 1–21), ICU stay was 8 days (IQR 7–22), and total hospital stay was 17 days (IQR 11–26).

Main post-operative complications included infection (38.7%), the most common being pneumonia, reperfusion edema (25.8%), and supraventricular arrhythmias (19.4%) (Table 2). In the PE group, 33% presented post-operative residual PH, with an mPAP of 37±7mmHg.

Six patients (18.8%) died in the immediate post-operative period. Patients who died had a poorer hemodynamic profile than survivors, although the differences were not statistically significant (Table 3). When broken down by periods, surgical mortality in the PE group between 2000 and 2006 was 5 out of 16 cases (31.3%), while in patients operated between 2007 and 2012, the mortality rate was 1 out of 16 patients (6.3%).

Patients unsuitable for surgery and who refused the procedure (Fig. 1) were treated with specific PH drugs or with calcium antagonists (MT group). The most commonly used specific PHA drugs were ERAs (49%), followed by PDE inhibitors (31%). Only 1 patient needed to receive combined therapy with 2 specific drugs (prostanoids and PDE inhibitors). Three patients were included in a clinical trial in which they initially received riociguat or placebo for 4 months, followed by riociguat. Patients with a vasodilator response classified as positive on pulmonary vascular reactivity testing began treatment with calcium antagonists (10%). Two patients in the MT group were evaluated for transplant, although the procedure was ultimately ruled out.

Overall 1-, 3-, and 5-year survival in the MT group was 83%, 69%, and 69%, respectively, and in the PE group it was 72%, 67%, and 67%, respectively (Fig. 2A). Conditional survival in patients in the PE group (those alive 100 days after intervention) was 95% at 1 year and 88% at 5 years (Fig. 2B). Patients undergoing PE between 2000 and 2006 had an immediate survival rate of 69%, and a 1-year survival rate of 59%. In patients operated between 2007 and 2012, immediate survival was 94% and 1-year survival was 86% (Fig. 3).

Fig. 2.

Survival (Kaplan–Meier) of patients with chronic thromboembolic pulmonary hypertension treated with pulmonary endarterectomy (PE) (solid line) or medical treatment (MT) (dashed line). Figure A shows overall survival of the PE group. Figure B shows conditional survival (patients alive 100 days after intervention) in the PE group.

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Fig. 3.

Survival of patients with chronic thromboembolic pulmonary hypertension receiving medical treatment (MT) or pulmonary endarterectomy (PE). The latter group was analyzed in 2 parts: patients operated in the 2000–2006 period and patients operated in the 2007–2012 period. One-year survival results for all groups and immediate postoperative (postop.) survival in patients undergoing PE are shown.

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The clinical course of the PE group and the MT group is summarized in Table 4, showing that all patients in the PE group presented FC I–II and achieved a greater distance in the 6MWT. Compared with pre-treatment values (in both PE and MT), a greater increase in the distance covered in the 6MWT and greater reduction in mPAP and PVR were seen in the PE group, compared to the MT group (Fig. 4).

Fig. 4.

Changes in follow-up (6–24 months) in patients with chronic thromboembolic pulmonary hypertension receiving medical treatment (MT) or pulmonary endarterectomy (PE): distance walked in 6min in meters (m), mean pulmonary arterial pressure (mPAP), cardiac index, and pulmonary vascular resistance (PVR).

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Only 33% of the operated patients had residual pulmonary hypertension requiring specific therapy.

At present, the indication of drug treatment in CTEPH is limited to (1) patients with residual PH after PE, and (2) patients not suitable for PE. These indications are based on expert recommendations,29 but there is little evidence of efficacy.18,19

In our center, 56% of patients considered suitable for surgery received specific therapy for PH in accordance with the recommendations in place during the study period2; this figure is similar to other studies.10 The aim of treatment was to reduce PVR before surgery, since a very high PVR (>1000dinscm−5) is one of the primary factors for reperfusion edema and adverse outcomes in the post-operative period.30 Some investigator groups are now advising against this preconditioning treatment because there is no evidence to support its efficacy and it may cause a delay in surgery.29,31

At the time of writing this article, no drug had yet been approved for the treatment of CTEPH in Spain, although the great majority of CTEPH patients considered unsuitable for surgery receive specific PH treatment,8,10,12 in accordance with clinical guidelines. In our center, 55% of patients were considered unsuitable for PE surgery, and specific treatment was administered to 90% of these cases. This indication is based on evidence of histological lesions indistinguishable from the typical lesions seen in patients with PAH.32 Data from specialized centers in the United Kingdom suggest that the prognosis of patients with inoperable CTEPH has improved in recent years.10 However, this initial functional improvement does not last beyond the first year after diagnosis. In our series of MT patients, a significant improvement was observed in functional capacity and in pulmonary hemodynamics 1 year after initiating specific therapy, although the values reached were lower than those observed in the PE group. These data are in line with those described by Condliffe et al.10

Long-term survival in patients considered inoperable who received medical treatment for PH in our series was similar to the rates reported by the U.K. group.10 However, long-term survival in MT patients was lower than conditional survival in the PE group and overall survival in the PE group operated during the second period of activity (2007–2012).

To conclude, analysis of the experience with CTEPH in our center confirms that PE provides clear hemodynamic improvements and better functional capacity in patients who successfully overcome the perioperative period; the disease can be cured in 67% of patients. After a learning period, the post-operative mortality rate in our center is currently within international standards.

These results, together with those previously reported by Blázquez et al.,18 should help increase the number of CTEPH patients undergoing PE in Spain. In accordance with current clinical guidelines, all patients with CTEPH should be offered the chance to be evaluated by an expert PE team, with the aim of identifying those who may benefit from this potentially curative treatment.