Research and Practice in Thrombosis and Haemostasis | 2021
Clinical significance of subsegmental pulmonary embolism: An ongoing controversy
Abstract
The incidence of pulmonary embolism (PE) has substantially increased since the introduction of multidetector computed tomography pulmonary angiography (CTPA) in the late 1990s,1 which has revolutionized the diagnosis of PE and has largely replaced other diagnostic exams.2 Multidetector CTPA allows visualization of even the small subsegmental pulmonary arteries due to its higher resolution compared to single-detector CTPA or ventilation-perfusion (V/Q) scanning, thus increasing the sensitivity for the detection of PE.3 The observed increase in PE incidence associated with the exploding use of CTPA coincided with the increase in the incidence of subsegmental PE (SSPE).4,5 SSPE nowadays account for approximately 15% of all acute PE diagnoses,6 and its incidence is likely to further increase with the continuous advancements in CT technology.1,6 The overall mortality associated with PEs has remained largely unchanged in the first decade after introduction of CTPA, despite a steep increase in PE incidence during this period.1 Although nationwide death certificate data of the United States suggests an increase in the rate of deaths caused by PE since 2008,7 findings from before 2008 implicate that the extra PE diagnosed with multidetector CTPA compared to less sensitive diagnostic modalities represent in average less severe disease. Accordingly, the smallest clots, that is, SSPEs, may be clinically irrelevant and potentially require a different therapeutic approach than segmental or more central PE.8 However, evidence to inform the optimal clinical management of patients with SSPE and no lower-limb deep vein thrombosis (DVT) is sparse, and thus considerable controversy exists whether or not these patients benefit from anticoagulation.9,10 The study by Fernández-Capitán et al in this issue of Research and Practice in Thrombosis and Haemostasis is a welcome addition to the limited body of evidence.11 Using prospectively collected data from the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) Registry, the authors investigated outcomes of patients anticoagulated for a first episode of symptomatic PE according to the most proximal anatomic location of PE. Among 15 963 patients with acute PE from 24 countries, 834 (5.2%) patients had an SSPE, while 3797 (24%) and 11 332 (71%) patients had a segmental and more central PE, respectively. Among those with an SSPE, a total of 198 (24%) patients had a concomitant lower-limb DVT, 242 (29%) had no DVT on ultrasound, and the remaining 394 (47%) had no documented ultrasound examination. The main finding of the study is an almost twofold increased risk of recurrent PE in patients with an SSPE compared to those with a segmental or more central PE (unadjusted hazard ratio [HR], 1.93; 95% confidence interval [CI], 1.16-3.32; and multivariable adjusted HR, 1.75; 95% CI, 1.02-3.03 compared to central PE). The authors investigated explanations for this unexpected finding, but results remained similar after adjustment for potential confounders, accounting for competing events (ie, non–PE-related death), and exclusion of patients with cancer. Moreover, outcomes did not differ according to the presence and absence of lower-limb DVT. Crude rates of recurrent DVT, major bleeding, and all-cause death were similar among the three groups. The results reported by Fernández-Capitán et al come from the largest study to date comparing outcomes in patients with SSPE and those with more proximal PE. The main result of an increased risk of recurrent PE in patients with SSPE is unexpected and should be interpreted with caution, since there seems to be little biological plausibility for this finding. Nonetheless, the results of the study confirm that SSPE is not per se a benign disease; in this regard, they are consistent with previous studies which have