Ann Thorac Surg 1998;66:1919-1924
© 1998 The Society of Thoracic Surgeons
Original Articles
Operation for chronic pulmonary thromboembolism accompanied by thrombophilia in 8 patients
Motomi Ando, MDa,
Shinichi Takamoto, MDa,
Yutaka Okita, MDa,
Ritsu Matsukawa, MDa,
Norifumi Nakanishi, MDb,
Shingo Kyotani, MDb,
Toru Satoh, MDb
a Cardiovascular Surgery, National Cardiovascular Center, Osaka, Japan
b Internal Medicine, National Cardiovascular Center, Osaka, Japan
Accepted for publication June 5, 1998.
Address reprint requests to Dr Ando, Department of Cardiovascular Surgery, National Cardiovascular Center, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan
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Abstract
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Background. Medical therapy for chronic pulmonary thromboembolism is limited, and surgical treatment has become more frequent recently. We have performed pulmonary thromboendarterectomy on 8 patients with chronic pulmonary thromboembolism accompanied by thrombophilia.
Methods. The patients were 6 men and 2 women aged 21 to 56 years (mean, 35 years). Five patients had antiphospholipid syndrome, 2 had protein C deficiency, and 1 had congenital antithrombin III deficiency. The preoperative condition was New York Heart Association functional class III in 5 and class IV in 3. Hypoxemia, marked pulmonary hypertension (mean pulmonary artery pressure, 47 ± 6.7 mm Hg), and low cardiac output were observed in all patients. After a median sternotomy, deep hypothermia was induced using a cardiopulmonary bypass, and pulmonary thromboendarterectomy in the bilateral pulmonary arteries was performed under intermittent circulatory arrest.
Results. There were no operative deaths. Long-term respiratory management was needed postoperatively by 3 patients. In the remaining 5 patients, no reperfusion injury was observed. The arterial blood oxygen concentration improved, and the mean pulmonary pressure decreased to 16 ± 5.5 mm Hg. The cardiac output also increased, and New York Heart Association functional class improved to I in 4 and II in 4 patients.
Conclusions. Pulmonary thromboendarterectomy under deep hypothermic intermittent circulatory arrest was effective for chronic pulmonary thromboembolism accompanied by thrombophilia for which medical treatment is of limited value.
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Introduction
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Medical treatment for chronic pulmonary thromboembolism (CPTE) is limited, and recently surgical treatment has become more widely performed. We performed pulmonary thromboendarterectomy (PTE) by median sternotomy under deep hypothermia and circulatory arrest on 8 patients with CPTE accompanied by antiphospholipid syndrome (APS) or protein C (PC) deficiency or congenital antithrombin III (AT III) deficiency as a complication of thrombophilia and observed good clinical results.
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Material and methods
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Patients
Eight patients had undergone PTE during the past 3 years (Table 1 ). The patients were 6 men and 2 women aged 21 to 56 years (mean, 35 years). They were admitted with dyspnea. The preoperative condition was New York Heart Association functional class III in 5 patients and class IV in 3. Five patients had APS, two had PC deficiency, and one had congenital AT III deficincy as a complication of thrombophilia. Hypoxemia was observed in all patients. Mean arterial oxygen tension was 62 mm Hg in room air. Cardiac catheterization showed marked pulmonary hypertension (mean pulmonary artery pressure, 47 ± 6.7 mm Hg), and revealed low cardiac output (mean cardiac output, 3.3 L/min). Total pulmonary resistance ranged from 958 to 1,293 dynes · sec · cm-5 (mean, 1,127 ± 130 dynes). Pulmonary arteriograms showed occlusion and stenosis from the lobar to segmental arteries. Figures 1 and 2 show preoperative pulmonary arteriograms for 4 patients. Lung perfusion scintigrams revealed multiple defects in the right and left lungs (Fig 3 ). Pulmonary angioscopy confirmed organized thrombi, and intravascular ultrasound revealed thickening of the pulmonary arterial walls in both lungs. Echocardiography showed massive tricuspid regurgitation on 3 patients. Deep vein thrombosis was established on 6 patients. After insertion of an inferior vena cava filter, operation was performed.
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Fig 1. Preoperative and postoperative pulmonary arteriograms; (A) patient 2 (case 2), (B) patient 3 (case 3).
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Fig 2. Preoperative and postoperative pulmonary arteriograms; (A) patient 7 (case 7), (B) patient 8 (case 8).
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Fig 3. Preoperative and postoperative lung perfusion scintigrams (A) patient 1 (case 1), (B) patient 6 (case 6), (C) patient 8 (case 8).
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Surgical techniques
After conducting median sternotomy, venous cannulas were inserted into the superior and inferior venae cavae, and an arterial cannula into the ascending aorta, and cardiopulmonary bypass was initiated. A vent tube was inserted through the right superior pulmonary vein. During cooling, the superior vena cava was freed. The anterior surfaces of the right and left pulmonary arteries were exposed to the pericardium attachment site. The PTE was initially performed on the right pulmonary. The right pulmonary artery was incised between the ascending aorta and superior vena cava. The dissecting plane was detected on the posterior wall. When the pharyngeal temperature reached 16°C, the ascending aorta was clamped, cardioplegic solution infused, and circulation arrested. The PTE was performed using a Jamieson’s stripper in the tunica media in the peripheral direction. After completion of the procedure, systemic circulation was resumed and the right pulmonary artery sutured. Next, the left pulmonary artery was incised, the dissecting plane was detected under circulatory arrest, and PTE was performed. To obtain a blood-free operative field, intermittent circulatory arrest was mandatory. The left pulmonary artery was sutured. Finally, tricuspid annuloplasty was done by Kay’s method on 3 patients. After the restoration of temperature to normal levels, the patients were weaned from the cardiopulmonary bypass.
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Results
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Table 2 shows results during operation. The duration of cardiopulmonary bypass was 172 to 325 minutes (mean, 233 ± 46 minutes), the duration of cardiac arrest was 90 to 183 minutes (mean, 127 ± 30 minutes), and the duration of circulatory arrest was 28 to 78 minutes (mean, 58 ± 19 minutes). Allotransfusion was performed on 1 patient, but the operation was carried out with autologous transfusion alone on the other 7 patients. Figure 4 shows resected specimens on the 6 patients. In 8 patients, the organized thrombi could be adequately resected from the pulmonary artery. Long-term respiratory management was needed for 1 patient in whom ascending aortic replacement was performed due to acute intraoperative aortic dissection (patient 2), 1 who had pneumonia preoperatively (patient 5), and 1 who showed mild reperfusion edema in both lungs immediately after the operation and had liver dysfunction preoperatively (patient 6). In the remaining 5 patients, no postoperative reperfusion injury was observed, and the duration of the stay in the intensive care unit was short (Table 2).
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Fig 4. Surgically removed thromboemboli from both pulmonary arteries in 6 patients. (A) patient 2, (B) patient 4, (C) patient 5, (D) patient 6, (E) patient 7, (F) patient 8.
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Postoperative examination values are shown in Table 3. Marked improvements in the clinical condition were observed in all 8 patients. The arterial blood oxygen concentration improved, mean arterial oxygen tension was 79 7.5 mm Hg in room air. The mean pulmonary pressure decreased to 11 to 27 mm Hg (mean, 16 ± 5.5 mm Hg). The cardiac output also increased (mean, 6.5 ± 1.7 L/min). Total pulmonary resistance decreased to 123 to 514 dynes · sec · cm-5 (mean, 228 ± 136 dynes), and New York Heart Association functional class was improved to I in 4 and II in 4 patients. Figure 5 showed the change of mean pulmonary arterial pressure and total pulmonary resistance before and after surgery. Pulmonary arteriograms (Figs 1 and 2) and lung perfusion scintigrams (Fig 3) showed the improvement in both lungs. Concerning the long-term results, 1 patient died of digestive tract bleeding after 1 year, but the other 7 patients remain well.
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Fig 5. The change of mean pulmonary arterial pressure (PAPm) and total pulmonary resistance (TPR) before and after operation.
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Comment
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Pulmonary thromboemboli normally resolve by active fibrinolysis. But in the cases of CPTE, it has been suggested that the main cause is that thrombi formed in the deep veins of the four limbs are repeatedly detached and become chronic when not dissolved in the pulmonary artery [1]. Chronic pulmonary thromboembolism develops without apparent cause in many patients, but is caused by blood coagulation abnormalities in some. The blood coagulation abnormalities include AT III, PC, or protein S deficiency or APS.
Congenital deficiencies of anticoagulation factors in the plasma predispose to thrombosis. In particular, congenital AT III deficiency gives a higher risk of thrombosis than deficiencies of other anticoagulation factors. Antithrombin III is a serine protease inhibitor and plays an important role in the control of blood coagulation. The incidence of congenital AT III deficiency is reported to be 1 in 2,000 to 5,000 [2], and thromboembolism develops after pregnancy, trauma, or operation. Thromboembolism itself occurs mainly in deep veins of the lower limbs, pulmonary arteries or mesenteric vein, and lesions in these areas account for 2% to 6% of all patients. Thrombosis develops by the age of 10 years in about 5% of patients and by the age of 30 years in about 65% [3].
The PC system is a natural profibrinolytic system consisting of PC and protein S, which are vitamin K-dependent plasma proteins, and thrombomodulin, a surface protein of endothelial cells. Together they set off a cascade that produces PC. This inactivates factors V and VIII and neutralizes the inhibitor of tissue-type plasminogen activator [4]. There is an autosomal dominant form of PC deficiency that has variable expression. Affected patients have a history of venous thromboembolism with superficial thrombophlebitis. These thromboses account for 7% to 12% of all cases of venous thrombosis in young patients. Thrombosis also develops by the age of 30 years in about 50% of patients and by the age of 40 years in about 80% [5].
Antiphospholipid syndrome induces systemic arterial or venous thrombosis, habitual abortion, and thrombocytopenia, and the complication rate of deep vein thrombosis or PTE is also high. It has been reported that pulmonary thromboembolism is observed in 20% of the patients with APS [6]. As antiphospholipid antibodies, anticardiolipin antibody and lupus anticoagulant were observed in our patients. However, the association between these antibodies and thrombosis susceptibility remains unclear. The APS was reported to often complicate various autoimmune diseases such as systemic lupus erythematosus [7]. The 8 patients reported in this study had congenital AT III deficiency or PC deficiency or APS as a thrombophilia, and 6 patients also showed deep vein thrombosis. Therefore, it was strongly suspected that CPTE was caused by blood coagulation abnormalities. There have been only a few reports of surgically treated patients with CPTE who had a thrombophilia [8, 9]. Abnormalities, such as lupus anticoagulant, PC deficiency, and AT III deficiency, are found in approximately 10% of patients [9]. In our 25 patients with CPTE who were surgically treated, 8 patients (32%) had a thrombophilia.
Chronic pulmonary hromboembolism is a serious disease that induces hypoxemia and pulmonary hypertension, which eventually lead to respiratory failure and right heart failure. It is resistant to medical treatment, therefore PTE has been frequently performed as the surgical treatment for CPTE in recent years [9–12]. The surgical indications for PTE include a pulmonary arterial mean pressure of 30 mm Hg or more, a pulmonary vascular resistance of 300 dynes or more, thrombi that can be surgically approached and preservation of the pulmonary function without severe complications [9]. The PTE is performed unilaterally after thoracotomy [13] or by the median approach under deep hypothermic circulatory arrest [10, 12]. Using the latter method, lesions in the bilateral lungs can be treated simultaneously. In addition, there is a lower risk of pulmonary hemorrhage, and cardiac lesions as complications can also be treated. Because of these advantages, PTE under deep hypothermic circulatory arrest is a standard surgical procedure for this disease.
In PTE, the organized thrombi strongly adhered to the pulmonary artery wall should be resected in the media together with the intima. Therefore, the determination of the dissecting plane is of primary importance in this procedure. Second, dissection should be gradually advanced in the peripheral direction while the organized thrombi are pulled, and firm organized thrombi should be resected together with the intima. Third, a blood-free operative field should be obtained. For these reasons, deep hypothermic intermittent circulatory arrest is useful. The 8 patients presented in this study were good candidates for PTE. Operations were performed, and marked improvements in clinical symptoms were obtained.
In conclusion, we performed PTE under deep hypothermic intermittent circulatory arrest on 8 patients with chronic pulmonary thromboembolism accompanied by congenital AT III deficiency or PC deficiency or APS that predisposes to thrombosis. Medical treatment is often limited in patients with CPTE. Among our 8 patients, PTE under deep hypothermic circulatory arrest was very effective.
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Top
Abstract
Introduction
