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Forget "embolic burden" of pulmonary embolism: location is everything
In Most Patients with Pulmonary Embolism, Central Clot is Worse than Peripheral
Pulmonary embolism (PE) presents with a wide range of clinical severity and course. Management decisions (level of care, length of observation, and aggressive therapies such as thrombolysis) are generally based on a patient’s risk of a poor outcome. Guidelines recommend risk stratifying patients based on hemodynamic stability, presence of right ventricular dysfunction, and biomarkers. Overall clot burden on CT scan has not proven useful for predicting outcomes, even though it seems like it should. In a recent study in Chest, Maria Cristina Vedovati et al come to the conclusion that central PEs are higher risk than distal ones, even if the overall clot burden doesn’t matter.
What They Did
In a prospective, multicenter study out of Europe, 579 patients with acute symptomatic PE were evaluated for the ability of the anatomic localization and overall burden of emboli on multidetector CT angiography to predict 30 day all-cause mortality or clinical deterioration (shock, rescue thrombolysis, intubation, pressors, or CPR). Emboli were categorized as central (saddle or at least 1 main pulmonary artery), lobar (at least one lobar artery), or distal (segmental or subsegmental). Overall embolic burden was estimated by the obstructive index (OI). Models were controlled for age, gender, cancer diagnosis, troponin, and right ventricular dysfunction on echocardiography.
What They Found
Central PE was significantly associated with dyspnea, concomitant DVT, obesity (trend), elevated troponin, and right ventricular dysfunction on echocardiography.
In the overall cohort, death or deterioration occurred in about 11% of patients with central or lobar PEs, and ~6% of patients with peripheral PEs.
In hemodynamically stable patients, central PE was an independent predictor of death or deterioration; lobar PE was nearly so, both with hazard ratios of ~8. Distal PE was associated with lower risk (a hazard ratio about 0.12). In absolute terms, ~8% died or deteriorated in the central/lobar groups, and ~3% with peripheral PEs.
Saddle PE considered alone was not an independent predictor.
The overall burden of PE (using the obstructive index) was not associated with worse outcome.
Age > 75, right ventricular dysfunction, and hypotension were significant predictors of death or deterioration.
What It Means
Hemodynamically unstable patients are at high risk for poor outcomes, irrespective of the location and amount of clot they have. Most of these patients will go to the ICU, and many will be candidates for thrombolysis. In hemodynamically stable patients, PEs in the main pulmonary arteries seem to confer a higher risk of dying or deteriorating, so these patients might warrant higher levels of care and longer observation periods compared to lower risk segmental and subsegmental PEs. I am not, however, reassured from these data that lobar PEs are that much lower risk than central PEs because hazard ratios were similar and the lack of statistical significance for the lobar group might have be due to power issues (i.e., there were half as many patients in the lobar group). This study supports the incorporation of age and echocardiographic evidence of right ventricular dysfunction in risk stratification for PE. It's unfortunate that the authors did not add BNP to their model, being another readily available marker of right ventricular dysfunction clearly associated with poor outcomes in PE. Troponin is also a well-validated prognostic marker in PE, but appears not to have been an independent predictor in their model. Finally, the authors mention that the presence of right ventricular dilation measured on CT is also prognostic, and that adding it to clot localization for risk stratification would be very appealing in order to both diagnose and prognosticate PE on a single CT scan. I agree, so why didn't they look at the combined predictive value of both CT clot localization and right ventricular dimensions in this study? It would seem they had the data. Maria Christina Vedovati et al. Multidetector CT scan for Acute Pulmonary Embolism: Embolic Burden and Clinical Outcome. Chest 2012;142:1417-1424.