Journal of Thrombosis and Haemostasis, 11: 2103–2110 DOI: 10.1111/jth.

12420

ORIGINAL ARTICLE

Pulmonary embolism severity index accurately predicts

long-term mortality rate in patients hospitalized for acute
pulmonary embolism
F. DENTALI, N. RIVA, S. TURATO, S. GRAZIOLI, A. SQUIZZATO, L. STEIDL, L. GUASTI,
A . M . G R A N D I and W . A G E N O
Department of Clinical Medicine, Insubria University, Varese, Italy

To cite this article: Dentali F, Riva N, Turato S, Grazioli S, Squizzato A, Steidl L, Guasti L, Grandi AM, Ageno W. Pulmonary embolism
severity index accurately predicts long-term mortality rate in patients hospitalized for acute pulmonary embolism. J Thromb Haemost 2013; 11:
2103–10.

define the 6-month and 1-year mortality rates in PE

Summary. Background: The Pulmonary Embolism (PE) patients.
Severity Index (PESI) is a clinical prognostic rule that
accurately classifies PE patients into five risk classes with Keywords: clinical prediction rule; follow-up study;
increasing mortality. PESI score has been validated in mortality; prognosis; pulmonary embolism.
studies with a relatively short-term follow-up and its
accuracy in predicting long-term prognosis has never been
established. Methods: Consecutive patients admitted to
the tertiary care hospital of Varese (Italy) with an objec- Introduction
tively diagnosed PE between January 2005 and December
Pulmonary embolism (PE) is associated with a consider-
2009 were retrospectively included. Information on clini-
able mortality rate. A short-term adverse outcome at pre-
cal presentation, diagnostic work-up, risk factors, treat-
sentation is mainly related to the presence and severity of
ment and mortality during a 1-year follow-up was
hemodynamic instability. In the Management Strategy
collected. Results: Five hundred and thirty-eight patients
and Prognosis of Pulmonary Embolism Registry, the in-
were enrolled in this study. The mean age was 70.6 years
hospital mortality rate ranged from 8.1% in a group of
( SD 15.2), 44.4% of patients were male, and 27.9%
stable patients with acute right heart failure, to 25% in
had known cancer. One-year follow-up was available for
patients with cardiogenic shock or even 65% in those
96.1% of patients. The overall mortality rate was 23.2%
requiring cardiopulmonary resuscitation [1]. On the other
at 3 months, 30.2% at 6 months and 37.1% at
hand, a long-term adverse outcome mainly depends on
12 months. The discriminatory power of the PESI score
the presence and severity of concomitant diseases. In the
to predict long-term mortality, expressed as the area
Prospective Investigation of Pulmonary Embolism Diag-
under the ROC curve, was 0.77 (95%CI, 0.72–0.81) at
nosis Project, 23.8% of patients died within 1 year after
3 months, 0.77 (95%CI, 0.73–0.81) at 6 months and 0.79
the diagnosis of PE, mainly because of cancer, sepsis or
(95%CI, 0.75–0.82) at 12 months. The PESI score con-
underling cardiac diseases [2].
firmed its accurate prediction in patients without cancer.
The Pulmonary Embolism Severity Index (PESI) is a
Simplified PESI had a similar overall accuracy to the ori-
practical clinical prediction rule (CPR), which has been
ginal PESI at 3 and 6 months, but this was significantly
derived and validated in patients admitted to hospital
lower at 1 year. Conclusions: The results of this study
with PE [3]. PESI uses 11 predictors from the medical his-
suggest that PESI score may also be an accurate tool to
tory and physical examination, without the need for labo-
ratory parameters or imaging procedures (Table 1). This
model reliably stratifies patients into five risk classes with
Correspondence: Francesco Dentali, Unit
a Operativa Medicina I, increasing risk of short-term mortality, and is proposed
Ospedale di Circolo, Viale Borri 57, 21100 Varese, Italy. as a potential tool to guide initial intensity of treatment.
Tel.: +39 0332 278594; fax: +39 0332 278256.
PESI class I and II patients have a very low risk of
E-mail: fdentali@libero.it
adverse outcomes, with an in-hospital mortality of less
Received 24 April 2013
than 1%, and are potential candidates for outpatient
Manuscript handled by: I. Pabinger treatment or early hospital discharge [4]. Recently, a sim-
Final decision: F. R. Rosendaal, 22 September 2013 plified version of the original PESI, based on six variables

© 2013 International Society on Thrombosis and Haemostasis

2104 F. Dentali et al

Table 1 Prognostic variables and risk stratification of the Pulmonary probability perfusion lung scan with deep vein thrombosis
Embolism Severity Index (PESI). Adapted from Aujesky [3] (DVT) documented by compression ultrasonography.
Predictors Points assigned

Demographic characteristics Baseline data collection

Age (years) Age
Trained study personnel retrospectively recorded baseline
Male sex +10
Co-morbid illnesses patient characteristics, including the variables that com-
Cancer (previous or active) +30 prise the original PESI (age, gender, cancer, heart failure,
Heart failure +10 chronic lung disease, pulse ≥ 110 beats min 1, systolic
Chronic lung disease +10 blood pressure < 100 mmHg, respiratory rate ≥ 30 min 1,
Clinical findings
temperature < 36 °C, altered mental status and arterial
Pulse ≥ 110 min 1 +20
Systolic blood pressure < 100 mmHg +30 oxygen saturation < 90%). For the simplified PESI the
Respiratory rate ≥ 30 min 1 +20 following parameters were considered: age > 80 years,
Temperature < 36°C +20 cancer, chronic cardiopulmonary disease, pulse
Altered mental status (disorientation, lethargy, +60 ≥ 110 beats min 1, systolic blood pressure < 100 mmHg
stupor or coma)
and arterial oxygen saturation < 90%.
Arterial oxygen saturation < 90% (with or +20
without the administration of supplemental Data on the presence of concomitant DVT and medical
oxygen) history focusing on potential risk factors for thrombosis,
treatment and clinical outcome were gathered. Further-
Risk classes Points Risk stratification more, information on personal history of venous throm-
boembolism (VTE) was also collected. A positive
Class I ≤ 65 Very low risk
Class II 66–85 Low risk personal history of VTE was established if the patient
Class III 86–105 Intermediate risk had a previous objectively assessed episode of DVT,
Class IV 106–125 High risk splanchnic vein thrombosis or cerebral vein thrombosis.
Class V > 125 Very high risk In the case of previous PE, the patient was not eligible
for the study. PE was defined as provoked in the presence
of one of the following risk factors: cancer, recent sur-
gery, oral contraceptive (OC) use, pregnancy, puerperium,
only, has shown a similar prognostic accuracy in predict-
hormone replacement therapy (HRT), recent acute medi-
ing 30-day mortality, when compared with the original
cal disease or recent confinement to bed for ≥ 72 h. In
PESI [5]. These two CPRs are revealed to be accurate
the absence of the aforementioned predisposing factors,
also with a more extended, 90-day follow-up [6–8], but
PE was defined as unprovoked.
their ability in predicting longer term prognosis has never
Using the prognostic variables of the PESI score, we cal-
been established.
culated the risk class for each patient, and the proportion
The purpose of this study is to investigate the accuracy
of patients classified within each risk class. Missing values
of the original and simplified PESI to predict the 6-month
for all prognostic variables were assumed to be normal (a
and 1-year mortality rate in PE patients.
strategy used in the original derivation of the PESI) [3].
After discharge, most patients with PE are regularly fol-
lowed by the local anticoagulation clinic. Information on
Methods
clinical events during follow-up for these patients was first
collected using the computerized database of the clinic. If
Patient identification and eligibility
patients were not followed by the local clinic, or if follow-
All patients with an objective diagnosis of PE at the ter- up data were not available, patients were contacted by
tiary care hospital of Varese, Italy, from January 2005 to telephone or by a mailed questionnaire. At the time of
December 2009, were potentially eligible for this study. contact, information on vital status was collected. If death
Patients were identified using discharge codes according occurred, family members or the general practitioner were
to the 9th Clinical Modification International Classifica- asked about the possible cause of death. Death was judged
tion of Diseases (ICD-9-CM 415.19 and 415.11). Charts to be related to PE if confirmed by autopsy, or if death
of all potentially eligible patients were retrieved for followed a clinically severe, objectively diagnosed PE.
evaluation. Sudden or unexpected death was classified as a possible
Only adult patients with an objectively diagnosed first fatal PE.
episode of acute PE were included for the purpose of the The Institutional Review Board approved the study,
study. which was carried out and is reported according to the
The criteria used to establish the diagnosis of PE were Strengthening the Reporting of Observational Studies in
a positive spiral CT scan, pulmonary angiography, a Epidemiology (STROBE) guidelines for observational
high-probability perfusion lung scan, or intermediate studies [9].

© 2013 International Society on Thrombosis and Haemostasis


Statistical analyses
Continuous variables were expressed as mean plus or
minus the standard deviation (SD) or as median with
minimum and maximum values when data did not have a
normal distribution; categorical data are given as counts
and percentages.
Initially, patients were divided into five classes accord-
ing to the original PESI score. Class-specific mortality at
3, 6 and 12 months was compared. To assess the discrimi-
natory power of the PESI score to predict long-term mor-
tality, we measured the area under the receiver operating
characteristic (ROC) curves at 3, 6 and 12 months. The
overall mortality rate of low- (risk classes I and II) vs.
high-risk patients (risk classes III-V) at 3, 6 and
12 months was compared using Kaplan–Meier analysis
and the log-rank test.
We evaluated the effect of each PESI predictor at 12-
month follow-up, using a multivariable Cox model
including all the predictors of the PESI score. Further-
more, to explore the potential role of other predictors of
mortality in patients with PE, we performed a multivari-
able Cox regression analysis with backward elimination,
including the risk categories of the PESI score (low vs.
high-risk) together with the following variables: previous
acute coronary syndrome, previous cerebrovascular acci-
dent, peripheral artery disease, autoimmune disease, dia-
betes mellitus, history of chronic kidney disease, atrial
fibrillation, previous VTE (DVT, splanchnic or cerebral
vein thrombosis), chronic liver disease and dyslipidemia.
Variables with a P value < 0.05 were considered indepen-
dent predictors of mortality. In a separate Cox regres-
sion analysis, duration of anticoagulant therapy (less or
equal to 3 months vs. more than 3 months) has been
evaluated with respect to the risk categories of the PESI
score.
To explore the role of PESI in predicting mortality in
patients without cancer at baseline, we performed a sub-
analysis excluding patients with cancer and removing 30
points from each PESI class. To assess the accuracy of
PESI to predict overall mortality, we estimated sensitivity,
specificity, positive and negative predictive values and
likelihood ratios for low vs. high-risk patients. A positive
likelihood ratio indicates how much more likely it is that
patients who die are classified into PESI risk classes III,
IV and V relative to those who survive; a negative likeli-
hood ratio indicates how much less likely it is that
patients who die are classified in PESI risk classes I and
II compared with those who survive. Afterwards, all the
analyses were repeated dividing patients into two classes
according to the simplified PESI (0 points at low risk of
death, 1 or more at high risk of death).
To examine the predictive validity of the original and
simplified PESI, we compared the area under the ROC
curves using the ‘roccomp’ command in STATA [10].
© 2013 International Society on Thrombosis and Haemostasis
PESI score and long term mortality for acute PE 2105
All analyses were performed using SPSS 19.0 (SPSS
Inc, Chicago, IL, USA) and STATA 12 (StataCorp LP,
College Station, TX, USA).
Results
Baseline patient characteristics
The charts of 555 patients with an objective diagnosis of
PE were reviewed. Seventeen patients were excluded
because of a previous episode of PE, leaving 538 patients
diagnosed with a first episode of acute symptomatic PE
(Table 2). The median age was 73 years, ranging from 18
to 100 years; 239 (44.4%) patients were male. Diagnosis
of PE was obtained with spiral CT in 419 (77.9%)
patients and perfusion lung scan in 119 (22.1%) patients.
Concomitant DVT was present in 301 (55.9%) patients,
293 in the lower limbs, eight in the upper limbs. More-
over, six patients had a diagnosis of unusual site throm-
bosis, five in the splanchnic veins and one in the cerebral
veins, during the same hospitalization. The high preva-
lence of concomitant DVT is partly explained by a sys-
tematic search for the origin of the clot in most PE
patients at our institution. Sixty-one (11.3%) patients had
a personal history of VTE.
PE was unprovoked in 251 patients (46.7%) and can-
cer-related in 150 patients (27.9%). Risk factors for sec-
ondary events are listed in Table 2. Among the clinical
variables of the PESI score, 134 (24.9%) patients had
arterial oxygen saturation < 90% (with or without the
administration of supplemental oxygen), 92 (17.1%) had
a pulse ≥ 110 beats min 1, 60 (11.2%) had systolic blood
pressure < 100 mmHg, 30 (5.6%) had a temperature
< 36 °C, 25 (4.6%) had altered mental status (including
disorientation, lethargy, stupor or coma) and 12 (2.2%)
had a respiratory rate ≥ 30 min 1. According to the PESI
score, 172 patients were at low risk (classes I and II com-
bined) and 366 patients at intermediate-high risk (classes
III, IV and V combined).
During the hospitalization, 32 (5.9%) patients were
treated with thrombolysis, 76 (14.1%) with unfractionated
heparin and 410 (76.2%) patients received low-molecular-
weight heparin (LMWH). One patient had an inferior
vena cava filter placed and 19 (3.5%) patients were not
treated.
Follow-up and accuracy of original and simplified PESI
After discharge, no information was available for 13 out
of 538 patients. Data on 525 (97.6%) patients were there-
fore available for the 3-month follow-up, on 524 (97.4%)
for the 6-month follow-up and on 517 (96.1%) for the
12-month follow-up. Characteristics of patients with a
complete follow-up were not significantly different from
those of the entire population (data not shown).
2106 F. Dentali et al

Table 2 Baseline patient characteristics and risk-class distribution at 3, 6 and 12 months (chi-square for trend P < 0.001 for
Patients, n 538 all of these).
Provoked/unprovoked PE, n (%) 287 (53.3%)/251, (46.7%) At 1 year, mortality was 2.2% (95% CI, 0.4–11.6),
PESI predictors 10.8% (95% CI, 6.4–17.7), 33.1% (95% CI, 25.7–41.4),
Age (years), mean  SD 70.64  15.17 52.2% (95% CI, 43.1–61.1) and 72.3% (95% CI, 62.9–
median (range) 73 (17–100)
Male sex, n (%) 239 (44.4%)
80.1), respectively, in the five risk classes (Table 3). Signif-
Cancer, n (%) 150 (27.9%) icant PESI predictors of 1-year mortality at multivariable
Heart failure, n (%) 28 (5.2%) Cox regression analysis were: age, altered mental status,
Chronic lung disease, n (%) 87 (16.2%) cancer, pulse ≥ 110 min 1, systolic blood pressure
Temperature < 36°C, n (%) 30 (5.6%) < 100 mmHg and arterial oxygen saturation < 90%
Pulse ≥ 110 min 1, n (%) 92 (17.1%)
Systolic blood pressure < 100 60 (11.2%)
(Table 4).
mmHg, n (%) In a multivariable Cox regression analysis exploring the
Respiratory rate ≥ 30 min 1, n (%) 12 (2.2%) potential role of other predictors of mortality, a high-risk
Altered mental status, n (%) 25 (4.6%) category according to the PESI score was significantly
Arterial oxygen saturation < 90%, 134 (24.9%) associated with 1-year mortality rate (HR, 7.66; 95% CI,
n (%)
Risk-class distribution (PESI score)
4.44–13.22; P < 0.001), while previous VTE was signifi-
Class I, n (%) 49 (9.1%) cantly associated with 1-year survival (HR, 0.44; 95% CI,
Class II, n (%) 123 (22.9%) 0.23–0.82; P = 0.010).
Class III, n (%) 146 (27.1%) Duration of anticoagulant treatment did not emerge as
Class IV, n (%) 117 (21.7%) an independent prognostic predictor (HR, 0.52; 95% CI,
Class V, n (%) 103 (19.1%)
Other co-morbid illnesses
0.23–1.17; P = 0.113).
Concomitant DVT, n (%) 307 (57.1%) The Kaplan–Meier curves for cumulative survival of
Previous VTE*, n (%) 61 (11.3%) low-risk (classes I and II combined) vs. high-risk patients
Oral contraceptive treatment, n (%) 14 (2.6%) (classes III, IV and V combined) were significantly different
Recent bone fracture or 33 (6.1%) when compared at 3-, 6- and 12-month follow-up (log-rank
orthopedic surgery, n (%)
Chronic venous insufficiency, n (%) 15 (2.8%)
test P < 0.001 for these three comparisons) (Figure 1).
Myeloproliferative neoplasm, n (%) 6 (1.1%) We performed another survival analysis censoring
Concomitant infection at 67 (12.5%) patients with cancer-related mortality, in order to take
admission, n (%) competing risks into account, but the results did not
Previous cerebrovascular 70 (13.0%) change (data not shown).
accident, n (%)
Previous acute coronary 64 (11.9%)
When dichotomized as low risk vs. high risk, the PESI
syndrome, n (%) score had a sensitivity of 92.7% (95% CI, 87.8–95.8) and
Peripheral artery disease, n (%) 16 (3.0%) a specificity of 46.5% (95% CI, 41.0–52.0), a negative
Anamnesis of chronic kidney 49 (9.1%) predictive value of 91.5% (95% CI, 85.9–95.1) and a
disease, n (%) positive predictive value of 50.6% (95% CI, 45.2–55.9)
Atrial fibrillation, n (%) 65 (12.1%)
Autoimmune disease, n (%) 30 (5.6%)
for overall mortality at 1 year, with a negative likelihood
Diabetes mellitus, n (%) 61 (11.3%) ratio of 0.16 (95% CI, 0.09–0.26) and a positive likeli-
Dyslipidemia, n (%) 15 (2.8%) hood ratio of 1.73 (95% CI, 1.55–1.93) (Table 5).
Prosthetic cardiac valve, n (%) 3 (0.6%) The discriminatory power of the PESI score to predict
Chronic hepatopathy, n (%) 8 (1.5%) long-term mortality, expressed as the area under the
Congenital thrombophilia, n (%) 3 (0.6%)
ROC curve (AUC), was 0.77 (95% CI, 0.72–0.81) at
*Previous VTE includes DVT, splanchnic or cerebral vein thrombo- 3 months, 0.77 (95% CI, 0.73–0.81) at 6 months and 0.79
sis, because patients with previous PE were not eligible for this (95% CI, 0.75–0.82) at 12 months. On the other hand,
study. DVT, deep vein thrombosis; PE, pulmonary embolism; VTE, the PESI score has a moderate discriminatory power in
venous thromboembolism.
predicting cancer-related mortality (AUC, 0.74; 95% CI,
0.69–0.79), not-cancer-related mortality (AUC, 0.73; 95%
Overall, mortality rate was 23.2% (95% CI, 19.8–27.0) CI, 0.68–0.77), overall PE mortality (AUC, 0.73; 95% CI,
at 3 months, 30.2% (95% CI, 26.4–34.2) at 6 months and 0.68–0.78) or definite PE mortality (AUC, 0.74; 95% CI,
37.1% (95% CI, 33.1–41.4) at 12 months (Table 3). 0.69–0.79) at 12 months.
Of the 86 deaths that occurred during hospitalization, 63 Of note, PESI confirmed the accurate prediction of
were attributable to PE and 15 were possibly related to PE, overall mortality at 3 months (AUC, 0.74; 95% CI, 0.69–
while of the 106 deaths that occurred after discharge, five 0.80), 6 months (AUC, 0.74; 95% CI, 0.69–0.79) and
were fatal PE and seven were possible fatal PE. Cancer was 12 months (AUC, 0.74; 95% CI, 0.69–0.79) also in
responsible for 32.3% of the overall mortality (Table 3). patients without cancer.
Stratification into risk classes according to the original According to the simplified PESI score, 137 patients
PESI score was significantly correlated with mortality rate (26.1%) were classified as low risk and 388 (73.9%) as

© 2013 International Society on Thrombosis and Haemostasis

 PESI score and long term mortality for acute PE 2107

Table 3 Causes of death and comparison of risk-class-specific mortality according to PESI score

During hospital stay After discharge Total

(N = 86), n (%) (N = 106), n (%) (N = 192), n (%)

Causes of death
PE 63 (73.3%) 5 (4.7%) 68 (35.4%)
Possible fatal PE 15 (17.4%) 7 (6.6%) 22 (11.5%)
Cancer 8 (9.3%)* 54 (50.9%) 62 (32.3%)
Bleeding 2 (2.3%) 5 (4.7%) 7 (3.6%)
Infection 1 (1.2%) 5 (4.7%) 6 (3.1%)
Other cardiopathy 0 (0%) 5 (4.7%) 5 (2.6%)
Cerebrovascular accident 0 (0%) 5 (4.7%) 5 (2.6%)
Acute renal failure 1 (1.2%) 1 (0.9%) 2 (1.0%)
Unknown 0 (0%) 19 (17.9%) 19 (9.9%)

Mortality rate at 3 months, Mortality rate at 6 months, Mortality rate at 12 months,

n/N (%, 95% CI) n/N (%, 95% CI) n/N (%, 95% CI)

Risk-class-specific mortality
Overall 122/525 (23.2%, 19.8–27.0%) 158/524 (30.2%, 26.4–34.2%) 192/517 (37.1%, 33.1–41.4%)
Class I 0/48 (0%, 0–7.4%) 0/48 (0%, 0–7.4%) 1/45 (2.2%, 0.4–11.6%)
Class II 9/121 (7.4%, 4.0–13.5%) 12/121 (9.9%, 5.8–16.5%) 13/120 (10.8%, 6.4–17.7%)
Class III 25/139 (18.0%, 12.5–25.2%) 37/138 (26.8%, 20.1–34.8%) 45/136 (33.1%, 25.7–41.4%)
Class IV 33/115 (28.7%, 21.1–37.5%) 44/115 (38.3%, 29.9–47.4%) 60/115 (52.2%, 43.1–61.1%)
Class V 55/102 (53.9%, 44.3–63.3%) 65/102 (63.7%, 54.1–72.4%) 73/101 (72.3%, 62.9–80.1%)
Chi-square for < 0.001 < 0.001 < 0.001
trend, P value

*In four of these eight patients the concomitant presence of PE and cancer has been reported as cause of death in the hospital charts. n, num-
ber of events; N, number of patients available for follow-up; CI, confidence interval; PE, pulmonary embolism.

compared with the original PESI (AUC, 0.75; 95% CI,

Table 4 Effect of each PESI predictor at 12-month follow-up using
the multivariable Cox regression analysis 0.71–0.79 vs. AUC, 0.79; 95% CI, 0.75–0.82; P = 0.011)
(Table 5 and Figure 2).
HR (95% CI)

Age* 1.03 (1.02–1.04) Discussion

Male sex 1.10 (0.81–1.50)
Cancer 4.41 (3.23–6.01) In this study, we assessed the prognostic performance of
Heart failure 1.52 (0.87–2.65) PESI in stratifying patients according to their risk of
Chronic lung disease 1.03 (0.70–1.52)
long-term adverse outcomes. In particular, the results
Temperature < 36°C 1.52 (0.89–2.58)
Pulse ≥ 110 min 1 1.63 (1.15–2.32) of our study indicate that PESI may identify a subgroup
Systolic blood pressure < 100 mmHg 2.10 (1.42–3.10) of PE patients at low risk of overall mortality even at
Respiratory rate ≥ 30 min 1 0.58 (0.18–1.88) 12 months; that is < 5% in class I. Furthermore, we were
Altered mental status 4.72 (2.71–8.23) able to identify a large group of patients with a very high
Arterial oxygen saturation < 90% 1.45 (1.06–1.98)
risk of mortality at 12 months.
*The hazard ratio for age is for 1-year increase. HR, hazard ratio; Defining the prognosis of patients with an acute PE
CI, confidence interval. may have important clinical implications and may help
clinicians to allocate adequate resources in the manage-
high risk. At 1 year the simplified PESI score had a sensi- ment of these patients.
tivity of 95.8% (95% CI, 91.7–98.0) and a specificity of Despite a great amount of data available on short-term
38.2% (95% CI, 32.9–43.7), a negative predictive value of prognosis of PE patients, only a few studies have investi-
93.9% (95% CI, 88.0–97.2) and a positive predictive gated possible predictors of long-term prognosis in these
value of 47.8% (95% CI, 42.7–52.9) for overall mortality, patients [4,11,12]. Most data are only on the general natu-
with a negative likelihood ratio of 0.11 (95% CI, 0.05– ral history of PE patients without stratifying for prognos-
0.22) and a positive likelihood ratio of 1.55 (95% CI, tic risk factors or, more frequently, follow-up is limited to
1.42-1.70) (Table 5). the first 3–6 months of treatment [13,14]. However, few
The simplified PESI had a similar overall accuracy to studies suggest that some prognostic factors are indepen-
the original PESI at 3-month (P = 0.22) and at 6-month dently associated with long-term prognosis in PE patients.
follow-up (P = 0.40), whereas at 1 year the overall An association between patient-related factors (e.g. cancer
accuracy of the simplified PESI was significantly lower and renal insufficiency) and PE-related factors on

© 2013 International Society on Thrombosis and Haemostasis

2108 F. Dentali et al

were followed for a mean follow-up of 5.3 years. At the

1.0 Low risk patients multivariable analysis, the following variables were associ-
ated with long-term mortality: age > 75 years (RR, 2.73;
95% CI, 2.18–3.21), persistence of vascular pulmonary
0.8 obstruction > 30% after thrombolytic treatment (RR,
2.22; 95% CI, 1.69–2.74) and cancer (RR, 2.03; 95% CI,
Cumulative survival

1.40–2.65). Moreover, Ribeiro and colleagues [16] have

0.6 High risk patients
0.4
0.2
0.0
0 3 6 9
Months of follow-up
Fig. 1. Kaplan–Meier curves for low-risk (classes I and II) vs. high-
risk (classes III, IV and V) patients, according to PESI score.
admission (i.e. severity of clinical presentation, electrocar-
diogram and echocardiographic parameters) with adverse
outcomes both in the short term and after hospitalization
was previously shown [2,15]. Carson and colleagues [2]
prospectively followed 399 patients with PE for 1 year.
Co-morbidities associated with long-term mortality were:
the presence of cancer (relative risk [RR], 3.8; 95% CI,
2.3–6.4), left-sided congestive heart failure (RR, 2.7; 95%
CI, 1.5–4.6) and chronic lung disease (RR, 2.2; 95% CI,
1.2–4.0). Meneveau and colleagues [15] analyzed a registry
of 249 PE patients treated with thrombolytic drugs who
shown that PE patients with systolic pulmonary arterial
pressure of more than 50 mmHg at admission had a
higher risk of persistent pulmonary hypertension at 1
year, as well as an excess of mortality at 5 years.
Unfortunately, most of these studies were not able to
identify patients at low risk of death. To the best of our
knowledge, only two studies have investigated prognostic
clinical variables formally combined in a CPR to predict
long-term prognosis in PE patients [4]. Subramanian and
colleagues prospectively evaluated the performance of the
Geneva prognostic CPR in 105 PE patients at 3 and
12 12 months [17]. At the 12-month follow-up, 5/88 patients
(5.7%) with a score of two or less died and 8/17 patients
(47.1%) with a score of three or more died (P < 0.0001).
Yamaki and colleagues [18] investigated the accuracy in
predicting overall mortality and recurrent venous throm-
boembolism at 12 months of their own CPR in 203 PE
patients. The adverse event rates were 6.0% for the
low-risk group and 59.5% for the high-risk group.
Our study investigated the long-term prognostic accu-
racy of PESI. Several large cohorts have confirmed its
ability to predict the short-term mortality [4]. The PESI
was studied in 21 cohorts with a total of 22 127 patients,
has a Level 2 of evidence at McGinn’s scale for quality of
CPR development, and has been used for selecting
patients eligible for home treatment in a randomized con-
trolled trial [19]. Moreover, PESI identified 43% of PE
patients with in-hospital mortality of less than 1% (i.e.
the threshold proposed by both the European Society of

Table 5 Accuracy of the original and simplified PESI prognostic models to predict mortality for low vs. high risk patients

Original PESI score Simplified PESI score

3 months 6 months 12 months 3 months 6 months 12 months

(N = 525) (N = 524) (N = 517) (N = 525) (N = 524) (N = 517)

Sensitivity,% (95% CI) 92.6 (86.1–96.4) 92.4 (86.8–95.8) 92.7 (87.8–95.8) 96.7 (91.3–98.9) 96.8 (92.4–98.8) 95.8 (91.7–98.0)
Specificity,% (95% CI) 39.7 (34.9–44.7) 42.9 (37.8–48.1) 46.5 (41.0–52.0) 33.0 (28.5–37.9) 35.8 (30.9–41.0) 38.2 (32.9–43.7)
Positive predictive 31.7 (27.0–36.9) 41.1 (36.0–46.5) 50.6 (45.2–55.9) 30.4 (25.9–35.3) 39.4 (34.6–44.5) 47.8 (42.7–52.9)
value,% (95% CI)
Negative predictive 94.7 (89.8–97.4) 92.9 (87.6–96.1) 91.5 (85.9–95.1) 97.1 (92.2–99.1) 96.3 (91.2–98.6) 93.9 (88.0–97.2)
value,% (95% CI)
Positive likelihood 1.54 (1.40–1.69) 1.62 (1.47–1.79) 1.73 (1.55–1.93) 1.44 (1.34–1.56) 1.51 (1.39–1.64) 1.55 (1.42–1.70)
ratio (95% CI)
Negative likelihood 0.19 (0.10–0.35) 0.18 (0.10–0.31) 0.16 (0.09–0.26) 0.10 (0.04–0.26) 0.09 (0.04–0.21) 0.11 (0.05–0.22)
ratio (95% CI)
Area under the receiver 0.77 (0.72–0.81) 0.77 (0.73–0.81) 0.79 (0.75–0.82) 0.75 (0.70–0.79) 0.76 (0.72–0.80) 0.75 (0.71–0.79)
operating characteristics
curve (95% CI)

N, number of patients available for follow-up; CI, confidence interval.

© 2013 International Society on Thrombosis and Haemostasis


12-month follow up
1.00
0.75
Sensitivity
0.50
0.25
0.00
0.00 0.25 0.50 0.75
1-Specificity
Original PESI Simplified PESI
Fig. 2. ROC curves of the original and simplified PESI for mortality
at 12 months.
Cardiology and the American Heart Association for
defining low-risk PE patients). In our study, stratification
into risk classes according to PESI score was significantly
correlated with mortality rate for up to 12 months, with
a high sensitivity (92.7%) and high negative predictive
value (91.5%) for overall mortality also at 1 year. Fur-
thermore, apart from the high-risk category of the PESI
score, no other variable emerged as an independent pre-
dictor of long-term mortality. Vice versa, previous VTE
was significantly associated with 1-year survival, suggest-
ing that these patients might obtain early diagnosis and
premature treatment.
The simplified PESI score appeared to have a similar
accuracy to the original PESI at 3 and 6 months, whereas
at 1 year its accuracy was significantly lower compared
with the accuracy of the original PESI, suggesting caution
if used in defining the long-term prognosis of patients
with PE.
Of clinical note, in our cohort a lower percentage of
patients were classified as low risk according to the PESI
score (only 32%) and we found a higher mortality rate
compared with previous studies evaluating patients with
acute PE. The high mortality rate could be related to the
extensive prevalence of cancer and the older age of our
population, compared with previous studies. However,
because we enrolled all consecutive inpatients with an
objective diagnosis of PE, our study is likely to reflect
everyday clinical practice.
The main strengths of our study include the largest
cohort that has been investigated for the performance of a
prognostic CPR for long-term outcomes and less than 5%
of PE patients lost to follow-up. However, our paper has
potential limitations. First, the retrospective design of the
study means, per definition, lack of systematic reporting
of all data and misdiagnosis. However, objective criteria
were required to confirm the diagnosis of PE and less than
5% of data regarding the PESI prognostic variables were
© 2013 International Society on Thrombosis and Haemostasis
PESI score and long term mortality for acute PE 2109
missing. Because lacking information on vital parameters
in clinical practice, such as respiratory or heart rate, usu-
ally means that the patient is not tachypnoic or tachycar-
dic, these variables were assumed to be normal, a strategy
previously used in the original derivation of the PESI
score [3]. Moreover, given the retrospective design of our
study, the causes of death were retrieved from the hospital
records or other medical documentation, without perform-
ing an external independent adjudication. Second, we were
not able to compare the accuracy of the PESI with other
CPRs because not all the items of these scores were rou-
tinely collected in our hospital.
1.00
In conclusion, PESI may be an optimal tool for strati-
fying PE patients according to both their short-term and
long-term mortality risk. Before implementing the PESI
as a long-term prognostic CPR in clinical practice, future
studies should confirm our data.
Addendum
F. Dentali contributed to the conception and design of
the study, analysis and interpretation of data and drafted
the article. N. Riva contributed to analysis and interpre-
tation of data and drafted the article. S. Turato and S.
Grazioli contributed to acquisition, analysis and interpre-
tation of data. A. Squizzato and W. Ageno drafted the
article and contributed to interpretation of data and criti-
cal revision of the manuscript. L. Steidl, L. Guasti and A.
M. Grandi contributed to interpretation and critical revi-
sion of the manuscript. All authors provided final
approval of the manuscript.
Disclosure of Conflict of Interests
The authors state that they have no conflict of interests.
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