Is Clot Burden on CT Angiogram Predictive of Mortality in Pulmonary Thromboembolism?
Abstract & Commentary
By David J. Pierson MD, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle. Dr. Pierson reports no financial relationship relevant to this field of study. This article originally appeared in the December 2008 issue of Critical Care Alert. It was peer reviewed by William Thompson, MD. Dr. Thompson is Staff Pulmonologist, VA Medical Center; Associate Professor of Medicine, University of Washington. He reports no financial relationships relevant to this field of study.
Synopsis: A prospective study comparing angiographic clot burden score and ECG score in 105 patients with PE found no correlation between the two, and neither predictor correlated with 12-month mortality. In a second retrospective study of 33 consecutive patients with massive PE by conventional clinical criteria, there was also no correlation between findings on CT angiography and mortality.
Sources: Subramaniam RM, et al. Pulmonary embolism outcome: A prospective evaluation of CT pulmonary angiographic clot burden score and ECG score. AJR Am J Roentgenol. 2008;190:1599-1604; Findik S, et al. Massive pulmonary emboli and CT pulmonary angiography. Respiration 2008;76:403-412.
With pulmonary computed tomographic (CT) angiography increasingly being used to diagnose acute pulmonary thromboembolism (PE), it has become commonplace to report not only the presence of clot when the study is positive, but also an estimate of the clot burden. In at least some institutions, the CT angiograms of patients with large quantities of visualized thrombus are read out as "massive PE." By examining the assumed relationship between the CT angiographic findings and clinical outcomes in patients with PE, two recent articles shed light on the clinical appropriateness of using such terminology.
Subramaniam et al at Waikato Hospital in Hamilton, New Zealand, carried out a prospective study to examine the claimed predictive value of each of two published scoring schemes for patients with PE: the CT pulmonary angiographic burden score of Qanadli et al1 and an electrocardiographic (ECG) score correlated to the extent of pulmonary perfusion impairment.2 The CT score weighted different assessments of the site and degree of pulmonary arterial obstruction, the latter used to calculate the percentage of obstruction. The ECG score assigned varying weights to several measures related to right ventricular strain, such as right bundle branch block, precordial T wave inversion, and the S1Q3T3 pattern. Two CT angiographers independently determined the CT scores, and two clinicians independently determined the ECG score, for the 105 patients with positive CT angiograms of 523 consecutive patients who underwent evaluation. Correlations were sought between the two indices, and also with the patients' clinical outcomes, determined 12 months after diagnosis.
The mean (SD) clot burden score percentage was 23.7% (16.8%) and the mean (SD) ECG score was 2.4 (2.8) out of a possible 21. There was no significant correlation between the two indices at the time of diagnosis (r = 0.09; p = 0.39). At one year, 13 patients had died, and neither the CT clot burden score nor the ECG score correlated with whether they were alive or dead (all-cause mortality).
Findik et al at Ondokuz Mayis University, Samsun, Turkey, carried out a retrospective analysis of a different index of the extent of pulmonary arterial obstruction, along with clinical data and mortality, in 33 consecutive patients with massive PE. The latter was diagnosed by the presence of a systolic blood pressure < 90 mm Hg, syncope, and/or shock. All the patients had CT angiography and an assessment of right ventricular function. Hemodynamic severity was assessed by the extent of right ventricular dysfunction, the diameter of the main pulmonary artery, the shape of the interventricular septum, and the extent of obstruction to the pulmonary arterial circulation using a CT obstruction index.
All 33 patients had emboli in the central pulmonary arteries. All of them also had right ventricular dysfunction, which was judged to be severe in 94%. The shape of the interventricular septum was abnormal in all the patients, and the diameter of the main pulmonary artery was increased in 76% of them. The CT obstruction index was 50% or more in 85% of the patients. Twenty-eight (84%) of the patients survived, and Findik et al found no correlation between the CT angiographic findings and survival.
For decades, studies of the epidemiology and therapy of PE have used clinical criteria, not the estimated quantity of clot in the pulmonary arterial tree, to define "massive PE." The principal criteria are arterial hypotension and cardiogenic shock.3 Arterial hypotension is defined as a systolic blood pressure < 90 mm Hg, or a drop in systolic arterial pressure of at least 40 mm Hg for at least 15 minutes. The definition of shock is less quantitative but includes evidence of tissue hypoperfusion and hypoxia, such as altered level of consciousness, oliguria, and/or cool, clammy extremities. Patients with massive PE defined in this way have an early mortality of at least 15%, with the degree and persistence of hemodynamic compromise generally the most powerful predictors of in-hospital death. Although PE is commonly encountered among hospitalized patients, in one multicenter study of 2454 patients admitted with this diagnosis, only 4.2% of them met criteria for massive PE.4
Although both the Subramaniam and Findik studies raise issues of patient selection and other design features (and the Findik study was grossly underpowered for differences in mortality), they both emphasize that massive PE is a clinical diagnosis and not determined by the angiographic extent of visualized thrombus. This is important because of the implications of this diagnosis for thrombolysis and other therapy. The new American College of Physicians Evidence-Based Clinical Practice Guidelines (8th edition) emphasize the importance of clinical risk stratification, and recommend thrombolytic therapy in PE for patients with evidence of hemodynamic compromise.5 The guidelines do not include the clot burden, as visualized by CT angiography, in either defining massive PE or in selecting appropriate therapy.
1. Qanadli SD, et al. New CT index to quantify arterial obstruction in pulmonary embolism: comparison with angiographic index and echocardiography. AJR Am J Roentgenol. 2001;176:1415-1420.
2. Iles S, et al. ECG score predicts those with the greatest percentage of perfusion defects due to acute pulmonary thromboembolic disease. Chest. 2004;125: 1651-1656.
3. Kucher N, Goldhaber SZ. Management of massive pulmonary embolism. Circulation. 2005;112:e28-e32.
4. Goldhaber SZ, et al. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet. 1999;353:1386-1389.
5. Kearon C, et al. Antithrombotic therapy for venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest. 2008;133:454s-545s.