Prognostic value of right ventricular dilatation in patients with low-risk pulmonary embolism

Discussion

Our study investigated whether RVD assessed by MDCT was associated with an increased risk of adverse events in patients with acute normotensive PE and a sPESI score of 0. We found that a conventional RV/LV ratio of ≥0.9 or ≥1.0 by MDCT was not associated with an increase in our primary outcome, defined as a composite of all-cause mortality, symptomatic VTE recurrence or secondary shock.

The literature presents conflicting data on the prognostic value of an increased RV/LV ratio in patients with normotensive pulmonary embolism [6, 7, 10, 11, 13]. The RV/LV ratio, measured by transthoracic cardiac echography (TTE), has been associated with a higher risk of mortality in one meta-analysis, whereas RVD assessed by MDCT was not [13]. In the PROTECT study that followed 848 normotensive patients with PE, no association of MDCT-assessed RVD with 30-day all-cause mortality was observed [10]. In contrast, two recent meta-analyses and one recent cohort study reported an increased risk of death in patients with RVD by MDCT [6, 7, 11]. These studies were performed on patients with varying degrees of clinical severity and did not include only low-risk patients, according to their PESI or sPESI. RVD can be explained not only by acute PE but also by cardiopulmonary comorbidities. Since we included only patients with a sPESI of 0, all these patients did not have, by definition, any major pulmonary or cardiac comorbidities. As a result, RVD is more probably due to PE in these patients with a sPESI of 0.

We initially planned to define an optimal RV/LV ratio value to predict adverse events using ROC curve analysis. However, since the inferior confidence interval of the AUC was below 0.5, our data did not establish a relationship between the RV/LV ratio measured by MDCT and major complications in patients with PE and a sPESI of 0. Nevertheless, all three PE-related deaths in the study occurred in patients with a RV/LV ratio higher than 1.2 (supplementary table S2). Moreover, we observed that the rates of PE-related death or shock were significantly higher in patients with RV/LV ≥1.1 (table 5 and table S3). Although limited by the low number of events, our data suggest that patients with a sPESI of 0 and a higher than recommended cut-off RV/LV value on MDCT seem to be at higher risk for PE-related outcomes. Thus, even with the result of the ROC curve analysis, it seems that a cut-off value of MDCT-assessed RV/LV of ≥1.1 could be used to upgrade patients with a sPESI of 0 from the low to the intermediate-low risk class of the ESC. Also, in these patients it may be useful to perform TTE as it has been shown that RVD by TTE using a cut-off RV/LV ratio of 0.9 is associated with a higher risk of adverse events in patients with a low-risk PESI [14]. Of note, TTE was not performed in all patients included in this study; therefore, we cannot confirm these results. Another advantage of TTE is that it can, in some cases, diagnose right heart thrombi, which are associated with a worse prognosis [15]. This last finding warrants closer follow-up but it is unclear if a more aggressive treatment is needed [16, 17].

Even if our findings suggest a prognostic impact of a RV/LV ratio ≥1.1 in patients with a sPESI of 0, the impact of such a finding on the management of these patients remains unclear. Aujesky et al. [18] found that early outpatient treatment was safe for those with a low-risk PESI, without additional testing. Zondag et al. [19] also did not find an association between RVD by MDCT and a worse prognosis in low-risk patients selected using the Hestia criteria for outpatient treatment. More recently, den Exter et al. [8] found that measuring N-terminal pro-brain natriuretic peptide in low-risk patients using the Hestia criteria was not associated with a decrease in outcome events.

Our choice of primary composite outcome might necessitate further discussion. We included recurrent PE in the composite in order to be in accordance with most previously published PE prognostic studies. However, RVD could influence more specifically PE-related death or shock but not VTE recurrence and other causes of death. Of note, in our study, all six patients with a composite outcome had at least either PE-related death or shock (supplementary table S2). Therefore, the results remain unchanged if we excluded VTE recurrence from the composite and replace all-cause death by PE-related death.

There are several limitations to our study. First, it is a retrospective analysis of three prospective cohorts, which limits our conclusions. Second, although we could analyse many patients with a sPESI of 0, the number of events was very low, as expected in this subgroup of low-risk patients. Third, we cannot conclude that our results can apply to extreme RV/LV ratios, since only 139 patients (18%) had a RV/LV ratio larger than 1.2. The small number of patients with an extreme RV/LV ratio and the low number of outcome events may also explain why the AUC of RV/LV ratio lacked precision with a 95% CI including 0.5. Fourth, interobserver agreement could not be assessed for the measurements of the RV/LV ratio. However, it has been previously shown that interobserver agreement for the measurement of the RV/LV ratio in the transverse axial plan is good [11, 20]. Fifth, sPESI score was calculated retrospectively and missing data were assumed to be normal. However, less than 1% of the needed data for the calculation of sPESI were unavailable.

In conclusion, the current study confirms that RVD assessed by MDCT, using a conventional RV/LV ratio of ≥0.9 or ≥1.0 as a cut-off, is a common finding in patients with PE and a sPESI of 0, but does not add significant prognostic information for this low risk population. Nevertheless, physicians should still ask radiologists to measure the MDCT RV/LV ratio in those patients since higher values of the RV/LV ratio might still be associated with an increased risk of PE-related adverse events.