Introduction
Chronic thromboembolic pulmonary hypertension(chronic thromboembolic pulmonary hypertension, CTEPH) is a type of pulmonary artery obstructive disease. The main reason is thromboembolism leading to pulmonary occlusion, pulmonary vascular remodeling, and thenpulmonary hypertension. The 2013 International Pulmonary Hypertension Symposium also attributed pulmonary atherosclerosis, tumor cell embolism, pulmonary cysticercosis, foreign body embolism, and congenital acquired pulmonary stenosis to pulmonary hypertension.
Epidemiology
The incidence of chronic thromboembolic pulmonary hypertension is unknown. Acute pulmonary embolism is expected to occur between 500,000 and 600,000 people per year in the United States, and nearly 0.1% to 0.5% of those surviving will progress to CTEPH. In 2004, the New England Journal of Medicine published a study at the University of Padua in Italy: CTEPH occurs in 3.8% of patients with a history of acute pulmonary embolism. In 2013, Kim concluded nine clinical studies in the United States. The incidence of CTEPH after acute pulmonary embolism ranged from 0.4% to 9.1%.
Pathophysiology and clinical prognosis
The pathogenesis of CTEPH is still unknown. Previously considered lower limbsDeep vein thrombosisIt is an important cause of acute and chronic pulmonary embolism. However, nearly half of patients with CTEPH have not had clinical manifestations of acute embolism, and the clinical manifestations are occult, and 40% of patients have no deep vein thrombosis or deep vein disease. Other causes include systemic lupus erythematosus, antiphospholipid antibody syndrome, factor VIII overexpression, and protein C and protein S mutations. Other rare causes include chronic inflammatory diseases, myeloproliferative syndrome, and splenectomy. It has been found in recent years that iatrogenic (such as permanent pacemaker implantation) is also one of the causes of CTEPH.
When the thrombus is blocked by more than 40% of the pulmonary vascular bed, it will cause pulmonary hypertension. Chronic or repeated pulmonary embolism will lead to continuous increase of pulmonary vascular resistance. Some scholars have suggested that pulmonary hypertension is caused by pulmonary vascular remodeling (small blood vessel disease). From the original embolic event. CTEPH is extremely dying if left untreated and eventually died of respiratory failure and right heart failure.
Current status of treatment of CTEPH
Chronic thromboembolic pulmonary hypertension includes medication, surgical endarterectomy (PEA), interventional pulmonary balloon dilatation, and lung transplantation. Anticoagulant therapy is the basic treatment for CTEPH, and most patients need to take oral anticoagulant drugs for life. Currently, only a targeted drug, Leocitin, has a certain effect on reducing the pulmonary artery pressure in patients with CTEPH and improving the quality of life, but it is expensive and cannot be accepted by most patients. In 1956, Hollister of the United States first reported pulmonary endarterectomy for the treatment of CTEPH. PEA surgery has undergone a long process of exploration. From the 1950s to 1984, the San Diego Medical Center completed only 84 cases of pulmonary endarterectomy. By 2001, 1000 cases of PEA were performed worldwide, and the current annual PEA in the United States. The number of operations is only about 300. The San Diego Medical Center in Southern California is the world's largest surgical center for CTEPH. It has completed more than 3,000 PEA operations and established a mature treatment program for pulmonary endarterectomy. The mortality rate after 30 days has been controlled within 2.2%, nearly 5 years. The operative mortality rate has dropped to 1%. The average PEA mortality rate in 17 centers in Europe and Canada also fell to 4.7% (including those with less than 10 cases in some years). The level of PEA surgery in Asia has also made great progress in recent years: South Korea's Soo Han Kim reported a 10.8% mortality rate for PEA surgery; Japan's Ishida reported that the mortality rate of PEA surgery decreased from the first 14% (90s) to 7.5%; The mortality rate of hospital PEA surgery decreased from 11% in the early years to less than 2% in the past 5 years.
Preoperative evaluation of PEA
PEA surgery is the only solution that is believed to cure CTEPH. All patients diagnosed with CTEPH require an assessment of PEA surgery. Treatment decisions for CTEPH patients should be made through a multidisciplinary discussion by the CTEPH treatment team, including physicians, radiologists, and professional surgeons. The International Association of Pulmonary Hypertension emphasizes that for patients with CTEPH who are not considered to be inoperable, a second assessment of the availability of surgery is required at the second center with experience in PEA surgery.
The indication for PEA surgery is firstly regular anticoagulation for more than 3 months; secondly, patients with NYHA class II or higher, pulmonary vascular resistance >300dyne·s/cm5; third, pulmonary vascular imaging with chronic thrombosis, patients The degree of hemodynamic damage is consistent with its anatomical performance, and surgery is expected to be stripped; severe complications that affect surgery are also excluded. Some patients also have normal pulmonary vascular resistance at rest. They may not be able to diagnose CTEPH, but they are called chronic thromboembolic pulmonary vascular disease, especially those with unilateral embolism, but they do benefit from PEA surgery.
Ventilation/perfusion scans are not only used for diagnosis, but also to assess the feasibility of surgery by distinguishing between large vessels and small vessel lesions. The former presents multiple horizontal perfusion defects, the latter exhibits inconsistent spot-like changes with sensitivity and specificity, respectively. More than 96% and 90%. High-resolution computed tomography pulmonary angiography is increasingly used to diagnose and evaluate the feasibility of CTEPH, but CT has no proximal thrombus and can not rule out chronic diseases that can be treated by surgery. On the other hand, even if there is a central thrombus. The diagnosis of CTEPH cannot be completely determined. Right heart catheterization pulmonary angiography remains the gold standard for the diagnosis of chronic thrombotic lung disease and the feasibility of surgery. For experienced treatment centers, CTPA can be used as an alternative.
Contraindications to PEA surgery include comorbidities that severely affect surgery or limit postoperative survival, and pulmonary arterial pressure and embolic lesions do not match. In addition, distal lesions, high pulmonary vascular resistance, and advanced age are also factors that need to be considered. The classification of CTEPH is a factor that must be considered in the operation of PEA. The improvement of pulmonary artery pressure and pulmonary vascular resistance in type I and type II cases is significantly better than that of type III and type IV. Reports: Perioperative survival of type I and type II The rate of 98.1% was significantly higher than that of type III and type IV, 86.7%. 87.9% of patients with type I/II had improved NYHA cardiac function, while only 7 patients with type IV had improved cardiac function. Preoperative pulmonary vascular resistance (PVR) was associated with postoperative mortality, and Madani reported that perioperative mortality with preoperative PVR > 1000 dyne·s/cm 5 was more than twice as high as in other cases. The factors that evaluate the feasibility of surgery are also related to the surgeon's experience and skills, and the level of diagnosis, decision making, and postoperative management at the clinic. Among the 500 surgical patients reported by Santiago in 2003, type III and IV accounted for only 13.6%, while the results reported in 2012 showed that these two cases reached 47%, while perioperative mortality decreased significantly.
CTEPH pathological typing
The San Diego Medical Center classifies CTEPH into 4 types according to the thromboendothelial specimens that are explored and dissected during surgery. Type I is a blood clot in the main pulmonary artery and left and right pulmonary artery trunks, accounting for 12%; type II has no thrombus in the large pulmonary artery, but it is visible. The intima of the vascular thickening of the leaf artery was attached with grid-like fibers on the surface, accounting for 38%; the type III was the distal segment and the sub-segment level, accounting for 39.4%; the type IV was the distal small vessel disease, accounting for 7.6%. It is easy to access and easy to treat for type I type II lesions, and the pulmonary artery pressure and pulmonary vascular resistance after exfoliation are significantly decreased, which is a good indication for PEA; but for type III and type IV lesions, distal small vessels of lesion location It is not easy to treat during operation. Postoperative pulmonary blood pressure and pulmonary vascular resistance are not ideal. It is necessary to go to an experienced center for surgery.
PEA surgical plan
Endarterectomy was first performed in the 1960s and continued to improve over the next few years. Currently, the program of the University of Southern California San Diego Medical Center is the mainstream surgical program. Median sternotomy, deep hypothermic circulatory arrest, bilateral dissection to sub-segment level is the key to surgery. Deep hypothermia, intermittent discontinuation of circulation can avoid the collateral shunt from the systemic circulation to the pulmonary circulation, maintain a bloodless field of vision, and more completely peel the pulmonary vascular tree thrombus and endometrium to the sub-segment level. At the same time, deep hypothermia (19 ° C) is applied to prevent brain damage. Some medical centers have successfully carried out PEA that does not require a complete circulatory stop by using antegrade cerebral perfusion. A recent randomized study showed no significant difference in cognitive function between patients undergoing antegrade cerebral perfusion and surgery with conventional methods, while some patients discontinued antegrade cerebral perfusion due to excessive intraoperative blood loss. Complete stop circulation surgery.
It is especially important to find the correct anatomical level during the exfoliation process, as this level determines the level of all lung, lung or sub-segmental pulmonary arteries. For type I type II lesions, it is recommended to use "inversion" peeling from the proximal endometrium of the main pulmonary artery or left and right pulmonary artery; for type III and type IV lesions, direct exfoliation of the pulmonary artery segment opening or sub-segment level embolization can be used. The manner of stripping directly from the segment opening is accomplished by means of a fine-tipped tweezers and a peeling aspirator, and such surgical techniques require practice after mastering the conventional "inverted" peeling technique. It is necessary to avoid damage to the middle layer of the pulmonary artery during the exfoliation process. For cases of pulmonary artery thrombosis with pulmonary wall calcification, penetrating lesions of the pulmonary artery wall after calcified plaque dissection should be avoided.
After the bilateral endometrial ablation is completed, the circulation is resumed and rewarming begins. During this period, other operations such as coronary artery bypass grafting, valve repair replacement, and closure of atrial septal defect can be performed simultaneously. The tricuspid regurgitation secondary to CTEPH is functional reflux, and there is no need to repair. With the recovery of right ventricular function and right ventricular remodeling, reflux will be relieved. Patients with high residual pulmonary hypertension have a poor improvement in tricuspid regurgitation, which prolongs hospital stay and increases the incidence of atrial fibrillation. Ogino et al recommend tricuspid valvuloplasty in patients with residual pulmonary hypertension. Most centers advocate closing the patent foramen ovale. It is recommended to keep the foramen ovale open when considering postoperative residual pressure.
The combination of anesthesia and in vitro physicians during PEA surgery is especially important. Surgery needs to be carried out under the condition of deep hypothermic circulatory arrest, uniform cooling and rewarming of the whole body, and brain protection of spinal cord protection are not negligible links. Reduced cardiac output by volume control to reduce lung perfusion injury, vasoconstrictor drugs control the lung side branches. The San Diego Medical Center recommends the use of nitric oxide to control postoperative residual pulmonary hypertension.
For patients with CTEPH, especially those with a history of deep vein thrombosis, the San Diego Medical Center routinely implants an inferior vena cava filter to prevent recurrence of perioperative embolization. A survey of surgeons found that the ratio of filters used was 50:50. Most centers chose to place filters in high-risk patients with proximal deep vein thrombosis, but type III and IV lesions caused by gastrocnemius venous thrombosis. In patients, the use of the inferior vena cava filter is still controversial. There is currently no RCT experiment to support the conventional placement of the inferior vena cava filter, and the level of evidence used is low.
Surgical complications
PEA surgery is difficult, the learning curve is long, the incidence of surgical complications is high, and there are complications similar to other cardiac surgery, such as arrhythmia, hemorrhage, atelectasis, pleural effusion, pericardial effusion, diaphragmatic dysfunction, etc. However, reperfusion of pulmonary edema and residual pulmonary hypertension is a serious complication of PEA surgery that increases postoperative mortality.
Reperfusion pulmonary edema mainly occurs in the lung area after reperfusion after endometrial ablation, increased vascular permeability, manifested as alveolar hemorrhage and severe hypoxemia, significantly increased mechanical ventilation time and ICU stay time, the incidence rate is about 10 %-40%. Reperfusion pulmonary edema accounted for 60% of the short-term postoperatively, 30% within 48 hours after surgery, and only 10% after 48 hours. Severe preoperative pulmonary hypertension and postoperative residual pulmonary pressure increase the risk of reperfusion pulmonary edema. A retrospective study reported that preoperative interventional embolization of the bronchopulmonary collaterals reduced the incidence of reperfusion pulmonary edema, but this intervention was only a single-center retrospective report, with no prospective randomized controlled trials and multicenter data. In addition, trials have shown that minimizing the use of cardiotonic drugs and low tidal volume ventilation can reduce the incidence and mortality of reperfusion lung injury. The treatment of reperfusion pulmonary edema is mainly supportive treatment, using adequate mechanical ventilation and high PEEP, limiting water and diuresis to reduce lung water, avoiding high cardiac output and reducing oxygen consumption. For patients with severe respiratory distress syndrome, the lateral position is significantly better than the supine position. Inhaled NO and ECMO support are necessary for severe reperfusion of pulmonary edema.
The incidence of residual pulmonary hypertension after PEA is about 5-35%, which is a common cause of perioperative death. Postoperative severe residual pulmonary pressure is an important predictor of postoperative mortality. Irreversible pulmonary hypertension is the result of chronic thromboembolic lesions in the distal pulmonary artery or combined with small vessel disease. These lesions cannot be cured with PEA. A recent UK study found that 51% of patients with mPAP ≥ 25 mmHg and 3 patients with mPAP ≥ 30 mmHg should be treated with pulmonary vasodilator medication and followed up for a long time, mPAP ≥ 38 mmHg and PVR ≥ 425
Patients with dyne·s/cm5 had a poor long-term survival rate. It has also been reported that 31% of patients with PEA have residual pulmonary hypertension 3 months after surgery, but if the patient's symptoms and activity endurance are not considered, the 5-year survival rate is similar to that of patients not involved in pulmonary hypertension. Severe RPH after PEA and difficulty in treatment with right heart failure are usually supported by cardiotonic drugs, and diuresis improves right ventricular preload. Vasodilating drugs that lower pulmonary pressure are often ineffective and have a risk of causing systemic hypotension. Inhalation of NO or iloprost immediately after surgery can reduce pulmonary vascular resistance without affecting peripheral blood pressure.
When the reperfusion pulmonary edema and residual pulmonary hypertension are severe, the traditional treatment is ineffective. At this time, extracorporeal membrane oxygenation and (ECMO) and other circulation support measures are needed. In the presence of hemodynamic instability, intravenous-arterial ECMO is recommended, which is more in line with the patient's pathophysiological characteristics. The central approach of the cardiac cannula can be used, or the peripheral approach of the femoral arteriovenous cannula can be used. The blood is centrifuged through the tube and the lungs, causing a decrease in pulmonary arterial pressure and a decrease in right ventricular load while providing cardiac output and gas exchange. For hemodynamically stable lung reperfusion injury, venous-venous ECMO support is appropriate. An important principle of using ECMO to support treatment is that patients can recover within the expected support time. UCSD was treated with venous-venous ECMO, and the hospital survival rate was 30%. Berman reported venous-arterial ECMO due to poor hemodynamics and right ventricular dysfunction, with an average support time of 5 days and an in-hospital survival rate of 57%. ECMO has been recommended as the standard treatment for serious complications after PEA.
Postoperative anticoagulant therapy is easy to apply as soon as possible. It is recommended to be on the day of surgery, but bleeding complications should be ruled out. To avoid recurrence of thrombosis, all patients must have lifelong anticoagulant therapy.
Surgical outcome
PEA Surgery Results: The top-level pulmonary embolization surgery center has controlled operative mortality to 1-4%. The postoperative mortality of pulmonary vascular resistance greater than 500 dynes/s*cm5 (5.7%) was significantly higher than that of postoperative pulmonary vascular resistance less than 500 dynes/s*cm5 (1.2%). The San Diego Medical Center reported a significant improvement in mPAP 45.5 to 26.0 (mmHg) after PEA and cardiac output 4.3 to 5.6 (l/min). The international CTEPH database showed a reduction in pulmonary vascular resistance from 736 to 248 dyn.s/cm5, and data from the San Diego Medical Center showed a decrease from 719 to 253 dyn.s/cm5.
The San Diego Medical Center completed 308 cases of pulmonary endarterectomy from 1970 to 1994, with a 6-year survival rate of 75%. Recently, Corsico et al reported that 157 cases of pulmonary endarterectomy were completed from 1994 to 2006, and the 5-year survival rate was 84%. In Japan, Ishida et al reported that the 5-year and 10-year survival rates were 84% and 82%, respectively; The 10-year survival rate of PEA in Fuwai Hospital of Chinese Academy of Medical Sciences was 78%.
to sum up
Pulmonary endarterectomy is an effective treatment for patients with CTEPH. With the advancement of the surgical team, operative mortality and surgical outcomes have improved significantly. Most treatment centers have achieved lower hospital and long-term mortality, especially in In an experienced center, the distal type III lesion is no longer a surgical contraindication, and it can also achieve good results. However, not all CTEPH patients are eligible for surgical endarterectomy. The reason why surgery is difficult to perfect is related to anatomy and physiology. The key to success is a technically excellent surgery, anesthesia, extracorporeal circulation, postoperative monitoring and internal medicine. The overall teamwork. For chronic thromboembolic pulmonary hypertension, we face many challenges, bravely face challenges, and turn these challenges into an opportunity to cure the ills.
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