We conducted an observational, retrospective study to examine the baseline characteristics and short-term prognosis of a cohort of patients with stable and unstable acute symptomatic PE.

All patients with a diagnosis of symptomatic acute PE from the emergency department of the Hospital Ramon y Cajal (Madrid, Spain) between January 2003 and June 2016 were included consecutively. The diagnosis of PE was confirmed by computed tomography (CT) angiography findings of a partial or complete intraluminal defect surrounded by contrast medium or complete occlusion of a pulmonary artery in 2 consecutive CT slices.10 PE was diagnosed by ventilation/perfusion scintigraphy in patients with a high probability of PE according to PIOPED criteria11 (at least 1 segmental perfusion defect or 2 subsegmental defects with normal ventilation), or with clinical suspicion of PE, an inconclusive scintigraphy and diagnostic ultrasound of the lower limbs showing incomplete compressibility of the venous lumen as a sign of deep vein thrombosis (DVT).12

Patients received low molecular weight heparin (LMWH) at weight-adjusted doses every 12h for at least 5 days. Vitamin K antagonists were started along with LMWH between day 1 and day 3 of treatment, and LMWH was suspended when the international normalized ratio (INR) was stable and greater than 2.0. INR levels were monitored in accordance with the local practices of the center.

Recanalization treatment (thrombolytics, fragmentation or embolectomy) was used in hemodynamically unstable patients at the discretion of the treating physician. In general, mechanical fragmentation and embolectomy were reserved for unstable patients with contraindications for thrombolysis. A vena cava filter was inserted in patients with contraindication for anticoagulation (active bleeding or high risk of bleeding).

Study patients were classified into one or more of the following groups:ECS, in patients who had made a journey of more than 4h duration in the month before the diagnosis of PE, irrespective of the mode of transport.Cancer, active or in treatment, in the year prior to the diagnosis of PE.Surgery in the month prior to the diagnosis of PE.Immobilization, in non-surgical patients bedridden for 4 or more days in the month prior to the diagnosis of PE.Pregnancy, postpartum period, use of oral contraceptives in the month prior to the diagnosis of PE.Idiopathic, in the absence of any of the above-mentioned triggers.

The primary endpoint was defined as all-cause mortality in the month prior to diagnosis. Secondary endpoints were death due to the PE itself, objectively confirmed non-fatal thromboembolic relapse, and non-fatal major bleeding in the month following diagnosis.

Diagnostic criteria of non-fatal thrombotic recurrence were the presence of a new intraluminal defect on CT angiogram, or a new ventilation/perfusion defect on lung scintigraphy; new non-compressible venous segment or increase in the diameter of the thrombus by at least 4mm on lower limb ultrasonography.13

Non-fatal major bleeding was defined as bleeding requiring transfusion of at least 2 units of packed red blood cells, bleeding requiring surgery, or brain, retroperitoneal, or joint bleeding.14

Continuous variables were expressed as mean±standard deviation or median (interquartile range), as appropriate, and were compared with the Student t test or the Mann–Whitney U test for asymmetric data. Categorical variables were represented as percentages and compared using the Chi-square test or Fisher's exact test, if necessary.

Accumulated incidence curves were estimated using the Kaplan–Meier method and compared using the log rank test.15,16 A multivariate logistic regression model was constructed to evaluate the possible association between ECS and mortality.17 A maximum model of 14 variables selected on the basis of the published experience and expert opinion was developed. Variables were: (a) age; (b) sex; (c) chronic obstructive pulmonary disease (COPD); (d) congestive heart failure (CHF); (e) heart rate; (f) systolic blood pressure; (g) dyspnea; (h) chest pain; (i) syncope; (j) ECS; (k) cancer; (l) recent surgery; (m) immobilization, and (n) simplified Pulmonary Embolism Severity Index (PESI) scale.18 The analysis was constructed on the basis of the maximum model and by backward elimination of variables. Confounding variables (i.e., the coefficient of the variable evaluated was modified by more than 10% when the confounding variable was eliminated from the model) of the effect of ECS on the primary endpoint were maintained in the model. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were calculated.

SPSS software (version 19.0, SPSS Inc., Chicago, Illinois, USA) was used for the statistical analysis. Results with a 2-tailed value of P<.05 were considered statistically significant.

During the study period, 12629 patients with suspected acute symptomatic PE were evaluated and diagnosis was confirmed in 2445 (19.4%). Of these, 113 were lost to follow-up, so the final sample consisted of 2333 patients (1089 men and 1244 women), 95% of the population evaluated (Fig. 1). No statistically significant differences were found between the baseline variables of the patients who were included and those who were excluded. Approximately 70% of patients (1659/2333) were diagnosed by chest CT angiogram, 744 (32%) by high probability ventilation/perfusion scintigraphy, while 76 (3%) had negative chest studies and DVT confirmed by ultrasound of the lower limbs. Some patients had several simultaneous positive diagnostic tests.

Fig. 1.

Study patient flow chart. PE: pulmonary embolism.

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Study patient characteristics are shown in Table 1. The number of patients treated with inferior vena cava filters was low (2.2%; 52 of 2333 patients). Four percent (103 of 2333 patients) were treated with thrombolytics. Fewer patients in the ECS group were men (34% versus 47%; P<.01), and ECS patients were younger (55.8±14.2 vs 69.6±16.5; P<.001) and had less COPD (0% vs 8.1%; P<.001), heart failure (0.8% vs 6.0%; P<.01), cancer (4.8% vs 21%; P<.001), and history of recent hemorrhage (0% vs 3.4%; P=.03) A higher proportion of patients with ECS was classified as low risk according to the simplified PESI scale (45% vs 29%; P<.001). PE was more severe in patients with ECS, who presented more frequently with syncope (48% versus 14%; P<.001), tachycardia (37% vs 21%; P<.001), right ventricular dysfunction (31% vs 19%; P<.01), and myocardial damage (57% vs 28%; P<.001) than patients with idiopathic PE or PE due to other etiologies. More patients with ECS had residual DVT (45% vs 57%; P=.02). With regard to treatment, more patients with ECS received thrombolytic treatment (9.8% vs 4.1%; P<.01).

Of the 2333 patients, 213 (9.1%; 95% CI: 8.0–10.4) died during the first 30 days of follow-up (Table 2). Seventy-six patients (36%) died due to their PE, 59 (28%) due to cancer, 25 (12%) due to infection, 10 (4.7%) due to heart failure, 8 (3.8%) due to bleeding, and 35 (16%) due to other causes. Seventy-five patients presented a secondary event: 21 had an objectively confirmed thrombotic recurrence, 50 patients had non-fatal major bleeding, and 4 presented simultaneous bleeding and recurrence.

Patients with ECS had a significantly lower risk of all-cause death than patients with idiopathic PE or PE from other causes (log rank test, P<.01; Fig. 2). Mortality due to the PE itself in the first month of follow-up was similar in ECS and non-ECS patients (log rank test, P=.11). None of the ECS patients had thromboembolic recurrence, and only 1 (0.8%) had non-fatal major bleeding in the first 30 days of follow-up.

Fig. 2.

Survival curve for the primary endpoint. Log rank test, P<.01.

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In the univariate analysis, age >80 years (OR: 1.82; 95% CI: 1.36–2.44; P<.001), some comorbidities, including COPD (OR: 2.15; 95% CI: 1.41–3.28; P<.001), heart failure (OR: 2.59; 95% CI: 1.64–4.07; P<.001), cancer (OR: 3.60; 95% CI: 2.68–4.82; P<.001), together with medical immobilization (OR: 1.82; 95% CI: 1.33–2.49; P<.001), clinical presentation [tachycardia (OR: 1.55; 95% CI: 1.13–2.12; P<.01) and hypotension (OR: 2.90; 95% CI: 1.99–4.23; P<.001)], and high risk on the simplified PESI scale (OR: 7.25; 95% CI: 4.11–12.80; P<.001) significantly increased the risk of all-cause death in the 30 days after PE diagnosis (Table 3). In contrast, a history of recent surgery (OR: 0.39; (95% CI: 0.19–0.81; P<.01) and ECS (OR: 0.16; 95% CI: 0.04–0.63; P<.01) were associated with a statistically significant reduction in the risk of death. In the multivariate analysis, ECS was independently associated with all-cause death during the first 30 days of follow-up (OR: 0.22; 95% CI: 0.05–0.94, P=.04) (Table 4). ECS was not independently associated with death due to the PE itself during the first 30 days of follow-up (OR: 0.37; 95% CI: 0.05–2.77; P<.33).