Clinic And Basic Research On Chronic Thromboembolic Pulmonary Hypertension After Acute Pulmonary Embolism

Objective:1. To document the incidence of CTEPH after acute PTE despite 3 months of therapeutic anticoagulation and evaluate risk factors for CTEPH and prognosis of CTEPH.2. To estimate the mortality of acute PTE and the cumulative incidence of CTPH after long-term follow up and evaluate risk factors for CTEPH after long-term follow up.3. To document if we can make the rabbits model of CTEPH after twice acute PTE and investigate the change of t-PA and PAI-1 in rabbits model of twice acute PTE.Methods:1. We enrolled 104 patients with CT angiography-proven PTE and calculated Wells score and revised Geneva score according to clinic symptoms.2. Recorded blood lab data (blood gas analysis, CK-MB, D-dimer and so on), Calculated the ECG score according to 12-lead ECG. PASP was estimated from the Doppler-estimated tricuspid valve regurgitant. Evaluated Qanadli obstruction index and Mastora obstruction index correlated with CTPA.3. Patients were treated with thrombolysis plus anticoagulation or anticoagulation only. Patients were followed up by telephone or clinic visit to assess the WHO cardiac functional grade. Echocardiography doppler and CTPA were performed regularly. The times and reasons of death and readmission were recorded during study period.4. Rabbits model of twice acute PTE was established by injection of auto-blood clots through 4F catheter by jugular vein. Monitored PASP by 4F pigtail catheter.5. The plasma levels of D-dimer, t-PA and PAI-1 was measured by ELISA. Observed pulmonary artery changes by HE stain. The expressions of t-PA and PAI-1 in pulmonary arterys were assessed by immunohistochemistry. The expressions of mRNA of t-PA and PAI-1 were assessed by RT-PCR.Results:1. Of the104 patients, seven patients were lost, two patients died during hospitalization, one died after hospital discharge but before follow up. Thus 94 patients were followed up on three months end point.19 patients were diagnosised CTEPH and the ratio of CTEPH was 20.2%(19/94).2. The mortality of CTEPH was higher than that of non-CTEPH after long-term follow up. The survival rate of 62 months was significantly different between two groups(53.5%vs 97.8%, P＜0.001).3. Gender, baseline PASP, recurrent PTE, diameter of right atrium, diameter of right ventricular, CK-MB, D-dimer and Wells scores were significantly different between CTEPH and non-CTEPH(P<0.05). Recurrent PTE (odds ratio,1335.4), male(odds ratio,35.2), higher baseline PASP (odds ratio,15.9 per 20mmHg increment) were risk factors for three months CTEPH.4. A few patients’PASP was decreased to normal after long-term anticoagulation therapy who were diagnosised CTEPH on three months. So the ratio of CTEPH after long-term follow up was down to 14.4%(14/97). 5. Baseline PASP, recurrent PTE, diameter of right atrium, diameter of right ventricular and CK-MB were significantly different between long-term CTEPH and non-CTEPH(P<0.05). Higher CK-MB (odds ratio,8.3), baseline pulmonary artery pressure(odds ratio,5.0 per 20mmHg increment)were risk factors for long-term CTEPH.6. Rabbits model of twice acute PTE was established by injection of auto-blood clots. Pulmonary artery pressure was monitored by 4F pigtail catheter. This method could help us to establish rabbits’CTEPH model after many times’PTE in future.7. The plasma level of D-dimer was increased transiently after injection of auto-blood clots. That of t-PA was decreased transiently then increased step by step. That of PAI-1 was decreased gradually in two hours after injection of auto-blood clots. The plasma levels of t-PA and PAI-1 were normal at one week after injection of auto-blood clots. The expression of PAI-1 in pulmonary arterys of one time PTE was decreased compared with that of control by immunohistochemistry. That of twice PTE was decreased further. The expression of t-PA in pulmonary arterys of one time and twice PTE was increased compared with that of control. The expressions of t-PA mRNA in pulmonary sample were not significantly different among three groups. The expressions of PAI-1 mRNA of one time PTE was decreased compared with that of control. That of twice PTE was decreased further.Conclusion:1. The ratio of CTEPH was 20.2% after acute PTE despite 3 months of therapeutic anticoagulation. The mortality of CTEPH was higher and the survival rate of CTEPH until 62 months was lower than that of non-CTEPH.2. Recurrent PTE, male and baseline PASP were the risk factors of 3 months CTPH.3. The ratio of CTEPH after long-term follow up was down to 14.4% because some patients’PASP was decreased to normal who were diagnosised CTEPH on 3 months.4. Higher CK-MB, higher baseline PASP increased the risk of long-term CTPH.5. Rabbits model of twice acute PTE was established by 4F catheter though jugular vein.6. The fibrolysis system of rabbits was returned to balance at one week after twice PTE. But that of pulmonary arterys with thrombus was more active.