Pulmonary thromboendarterectomy (PEA) is still the treatment of choice in patients with CTEPH. The expanded knowledge on PEA in the past few decades has resulted in a lower morality rate. The aims for performing thromboendarterectomy are to reduce PVR and to improve long-term performance (11).
Pulmonary thromboendarterectomy is associated with a higher chance of mortality than other routine cardiac operations and requires superior experience and skill (12,13). This study investigated the outcomes of 31 PEA cases in a medical center, with a high success rate and a low mortality rate. The first successful PEA was conducted by Ailison in 1960. Since then, more than 4,000 PEA operations have been performed across the world (14).
Among PEA centers, the University of California, San Diego, is the most prominent, with more than 3,000 surgeries and the lowest mortality rate (15). There are many published reports on its successful outcomes (15,16). The reported mortality rates in other centers vary between 5% and 24% depending on their previous experience (17,18).
This study showed that thromboendarterectomy drastically improved the patients’ hemodynamics and performance. In this single-center experience, the overall postoperative mortality (5%) was lower than the mean operative mortality rate. After the surgery, PVR and the mean PAP were considerably reduced.
In 500 patients reported by the San Diego Center, 37.4% were type I, 49% were type II, 16% were type III, and 1.6% were type IV (15). In our study, 87% had proximal involvement, and only 22% had distal involvement.
One reason for the number of successful operations and the low mortality rate was the preoperative examination of the patients and their correct selection. Before surgery, the patients were examined for microvascular involvement, and those with PVR higher than 1000 dyn.s/cm5 * were considered to be high-risk patients. This group was visited three times per day by the pulmonologist and the surgeon in the first five days after the surgery. In total, 27.5% of the patients had PVR higher than 1000 dyn.s/cm5, out of which 7.2% experienced reperfusion injury. According to some studies, severe pulmonary hypertension (PH) increases postoperative mortality (19). A common dilemma is the use of pulmonary vasodilator as a preoperative bridging therapy. There are many studies exploring the use of these drugs in patients who cannot undergo surgery, (20,21) out of which only one randomized controlled trial (RCT) evaluating riociguat reported its positive effects through increasing 6MWD (22).
Although there is no multicenter RCT exploring the use of these drugs as bridging therapy and their role in reducing the mortality rate, a few single-blind studies on the effect of bosentan on 25 CTEPH patients showed a mortality rate of 31% among recipients of bosentan versus 25% among controls (23). The STEPH registry did not show a between-group difference in complications; however, the multivariate analysis showed that the bridging therapy was associated with an increased mortality rate. One reason could be the delay in referral for surgery and the changes made by these drugs on intra-arterial specimens. According to the results of these studies, none of the patients with high PVR received pulmonary vasodilators in our center, and the surgery was performed as soon as possible after referral.
In situ thrombosis is a common potentially fatal preoperative misdiagnosis of CTEPH in patients with idiopathic pulmonary arterial hypertension (IPAH), which is secondary to endothelial injury (24,25).
In 2015, a general evaluation and revision of postoperative care was conducted in our medical center based on the protocols of San Diego Center, including constant visits by a pulmonologist, maintaining a low cardiac index (CI) after the surgery, and establishing urination to reduce and control complications, specifically reperfusion injury, which resulted in significant reductions in mortality.
In this case series, high preoperative PVR was the leading cause of complications, specifically reperfusion injury, and morality; 1 patient died with a PVR higher than 1000 dyn.s/cm5 and a mean PAP of 68 mmHg.
It is still uncertain whether other factors, such as high right arterial pressure, play a role in the development of such complications. The literature results showed a difference between patients with PVRs lower and higher than 1000 dyn.s/cm5. Statistical data showed that hemodynamic disorders with PVRs higher than 1000 dyn.s/cm5 and mean PAPs higher than 50 mmHg were associated with high postoperative mortality (26). Some studies introduced aging as a risk factor for postoperative complications and mortality (27). In contrast, in our study, there was no relationship between aging and postoperative complications, and PVR was recognized as the most important risk factor. Moreover, some patients were mechanically ventilated for longer amounts of time. Regarding the lower pulmonary function of older patients, age can be a cause of longer ventilation after pulmonary operations, specifically reperfusion injury, which was not correlated with age. In general, RPI may occur in 10-40% of patients (28,29), with 60% of cases immediately after surgery, 30% in the first 48 hours after surgery (30), and sometimes 48 hours after surgery. In our study, RPI occurred within the first 24 hours after surgery. We tried to keep diuresis under mechanical ventilation (MV) and positive-end expiratory pressure (PEEP) and the CI was kept less than 3L/min/m2 with vasopressor.
A single-center study into the role of steroids in reducing RPI did not show any between-group differences (28). We did not use steroids to treat or prevent RPI in our patients. Studies have shown that avoiding inotropic and vasodilators and using a tidal volume of 8 mL/kg could reduce the chance of RPI (9). In case of a severe RPI and a postoperative increase in CI to >3 L/min/m2, cardiac output reduction with vasopressors may lead to a reduction in capillary leakage and a reduction in RPI. We avoided prescribing inotropic drugs to reduce this complication and tried to keep the patient’s CI lower than 3 using vasopressors.
If severe RPI does not respond to routine treatments, veno-venous ECMO (VV-ECMO) can be used. A case series published by the San Diego Center explained the use of ECMO for 20 out of 179 patients undergoing surgery over a period of 16 years (31). In this study, the survival rate was 30% in patients using EMCO versus 94.2% in patients did not receive it. The mortality rate in seven patients receiving ECMO within 120 hours after surgery was 100%. The latest global symposium on pulmonary hypertension recommended that this surgery should be performed in centers with appropriate equipment and conditions for ECMO placement (32).
Among our participants, only one patient needed VV-ECMO due to severe RPI and the lack of response to routine treatments. This patient developed severe reperfusion injury within 6 hours after surgery and received VV-ECMO due to the lack of response to supportive and pharmaceutical treatments within 24 hours. The ECMO was successfully removed from the patient after 72 hours. This patient stayed in the ICU and received MV for a longer time compared to other patients; in addition, the patient’s preoperative PVR was approximately 1600 dynes.Sec-1.Cm-5 and there was evidence of involvement in the proximal region and lobar artery. In the rest, RPI was managed through pharmacological and supportive treatments, and ECMO was not needed. Another postoperative complication of thromboendarterectomy in patients with CTEPH was persistent PH. There is no uniform definition for persistent PH after surgery, and its extent depends on the variable definition. In a study in England, approximately 30% of the patients showed high postoperative PH, based on MPAP>25 or PVR>240 dyn.s/cm5 (33). However, their survival rate was 94%, and 82% of them were left untreated at Functional class I and II. Remained pulmonary hypertension and RV failure after thromboendarterectomy are the leading causes of early mortality.
In our study, the postoperative PH remained high in two patients (7%), which could be attributed to incomplete removal of the specimen in one case and microvascular involvement in the other, despite the successful operative outcome.
Bleeding is another probable complication after arterial thromboendarterectomy, which is generally due to either pericardial or airway bleeding. The reported extent of postoperative bleeding in the pericardium varies in different studies, ranging from 0.6 to 17% (34,35).
Pericardial bleeding may occur immediately after surgery or with a delay. In the first scenario, the patient is transferred to the operating room for bleeding control. In the second scenario, pericardial bleeding is controlled by temporary discontinuation of anticoagulants and drainage. Among our participants, two patients (8%) developed early postoperative pericardial bleeding and were transferred to the operating room for bleeding control.
However, management of airway bleeding due to arterial injury during surgery or RPI is a more complex problem. The first case is characterized by obvious and dark bleeding associated with the patient’s pulse. The second case is characterized by diffuse and pink bleeding, with no need for further surgery. There was only one patient with no severe hemoptysis, who immediately underwent bronchoscopy, and the bleeding was controlled.