Of the 116 patients in our study, CTPA at treatment discontinuation demonstrated thrombus resolution in 73 patients. The risk of residual and chronic thrombus was higher in patients with a D-dimer level higher than 500 µg/L and mPAP above 40 mmHg at treatment discontinuation. Our analysis of the relationship between thrombus on CTPA and dyspnea revealed that chronic and residual thrombus were less common in patients without dyspnea. In addition, we determined that high PAOI at time of diagnosis was associated with higher risk of chronic and residual thrombus. In addition, ROC curve analysis of D-dimer, mPAP, and PAOI at diagnosis showed that PAOI had higher sensitivity in detecting chronic and residual thrombus than the other two parameters.
PTE is one of the major emergencies for which morbidity and mortality rates are declining due to advances in early diagnosis and treatment . In treatment, the duration of secondary prophylaxis varies based on the risk factors present [9–11]. It was reported that 81% of 69 PTE patients followed up with CT angiography had complete resolution after 4 weeks . For this reason, follow-up with CTPA is not routinely done in patients being treated for PTE. However, this degree of complete resolution is seen in 50–80% of cases. Patients should be evaluated for long-term complications of PTE when discontinuing treatment .
As in acute PTE, dyspnea is one of the main symptoms of chronic thromboembolic pulmonary hypertension (CTEPH). A multicenter, prospective observational study aiming to develop a dyspnea-based screening algorithm to predict the incidence of CTEPH was conducted in 1699 acute PTE patients receiving treatment between March 2009 and November 2016 and published in 2018. In the study, patients were assessed by phone using a dyspnea questionnaire at 6, 12, and 24 months. Patients whose dyspnea complaints were class II or higher according to the New York Heart Association (NYHA) Functional Classification underwent ECHO examination. Radiological imaging (CTPA or V/Q scintigraphy) was performed in patients with suspected CTEPH based on these two steps. The negative predictive value of the first two steps was reported to be 99%. In the study, a significant statistical relationship was observed between dyspnea complaints and on follow-up imaging findings . Consistent with the results of that study, we observed that dyspnea was more common in patients with chronic and residual thrombus.
D-dimer is the smallest fibrin degradation product formed by the breakdown of cross-linked fibrin by plasmin. Its presence confirms both thrombin and plasmin formation. Serum D-dimer levels increase due to the simultaneous coagulation and fibrinolysis processes that occur in acute thromboses and are expected to regress with resolution of the thrombus in acute PTE [15, 16]. In a 2006 study of 608 acute PTE patients followed up with oral anticoagulant therapy for 3 months, treatment was discontinued in patients with normal D-dimer levels, while patients with high D-dimer levels were randomly assigned to either discontinue or continue treatment. Examinations performed 1 month later showed that patients with high D-dimer levels who discontinued treatment had a significantly higher recurrence rate than those who continued treatment. This study supported the significance of monitoring D-dimer level in determining the duration of acute PTE treatment .
ECHO is another examination commonly used to evaluate the likelihood of recurrent and chronic thrombus in acute PTE or PTE follow-up. The effects of pulmonary hypertension on the heart are evaluated by ECHO and mPAP is estimated by continuous wave Doppler measurements. The determination of mPAP is based on the maximal tricuspid regurgitation velocity and right atrial pressure. Some preoperative studies conducted in CTEPH patients demonstrated a correlation between the mPAP assessed by ECHO and mPAP assessed by catheterization . Therefore, ECHO is a useful, noninvasive method for the follow-up of long-term PTE complications. The center in which our study was conducted is one of the few high-altitude settlements in our country and the world, and elevated mPAP is frequently observed in our region due to chronic hypoxia. Using previous studies as a reference, an mPAP threshold of 40 mmHg was used in this study .
According to the data obtained in our study, we observed no statistically significant relationship between CTPA performed at diagnosis and the later development of chronic thrombus and residual thrombus. This suggests that chronic and residual thrombus evaluation should be done during follow-up on an individual basis and that even if initial thrombus load is high, the development of chronic and residual thrombus may be related to the patient, independent of treatment. In our evaluation of D-dimer and mPAP on ECHO, which are parameters commonly used in the diagnosis and treatment of PTE, we found that the probability of residual and chronic thrombus was lower if D-dimer level was below 500 µg/L and mPAP was below 40 mmHg. These findings may be attributed to a lower thrombus load resulting in both reduced D-dimer level, which is an indicator of fibrin degradation, and decreased right heart load. Our ROC analysis of PAOI at diagnosis of PTE and D-dimer level and mPAP at treatment discontinuation showed that PAOI was a better predictor of chronic and residual thrombus development than the other two parameters. An increase in the mPAP measured on ECHO may be triggered by many comorbidities and there may be differences between measurements. In our study, we tried to exclude conditions that may cause this. Similarly, although D-dimer level can serve as a guiding parameter in cases of suspected PTE, its level is affected by most comorbidities independent of thrombus load. As opposed to these, PAOI seems to have value as a better indicator of thrombus load. Therefore, we believe that priority should be given to patients with high PAOI at time of diagnosis when planning CTPA during follow-up.
This study has certain limitations. Most importantly, because this was a retrospective study, patients classified as having idiopathic PTE could not be evaluated for permanent risk factors and thrombophilia, and we were unable to obtain sufficient data regarding these parameters. Furthermore, because NYHA functional class was not used during dyspnea assessment, a detailed inquiry was not possible.
Based on the results of this study, we believe that evaluation with CTPA at treatment discontinuation is necessary in patients with elevated D-dimer, mPAP on ECHO above 40 mmHg, and especially high PAOI at diagnosis.
Ackknowledgement None to declare
Statement of Ethics Local ethics committee approved the study.