Figures
- FIGURE 1
Flow chart of patient enrolment and exclusion. Definitions are provided in the material and methods section of the online supplementary material. PE: pulmonary embolism; PERGO: Pulmonary Embolism Registry of Göttingen; LV: left ventricular; GFR: glomerular filtration rate.
- FIGURE 2
Copeptin plasma levels on admission and after 24 h in a subgroup of 56 patients.
- FIGURE 3
Receiver operating characteristic curve for copeptin, high-sensitivity troponin T (hsTnT) and N-terminal pro-brain natriuretic peptide (NT-proBNP) with regard to an adverse 30-day outcome. AUC: area under the curve.
- FIGURE 4
Risk assessment strategies of normotensive patients with pulmonary embolism. a) Risk assessment with a new biomarker-based strategy based on N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT) and copeptin. b) Risk assessment as proposed by the 2014 European Society of Cardiology (ESC) guideline. Number (%) of patients with an adverse 30-day outcome are shown for each step. HsTnT levels ≥14 pg·mL−1 and NT-proBNP levels ≥600 pg·mL−1 were defined as positive. #: in one patient with elevated hsTnT (109.8 pg·mL−1) levels, NT-proBNP plasma concentrations could not be measured on admission. Thus, stratification to risk classes using the biomarker-based strategy was not possible and the patient was excluded. Of note, in four patients neither multidetector computed tomography nor an echocardiographic examination for assessment of right ventricular function was performed; three of them were classified as intermediate–low risk and one patient as low risk using the ESC 2014 algorithm shown in b). Definitions are provided in the material and methods section of the online supplementary material. PE: pulmonary embolism; sPESI: simplified Pulmonary Embolism Severity Index; RV: right ventricular.
Tables
- TABLE 1
Medical history and baseline characteristics of the study patients
All study patients Copeptin <14 pmol·L−1 Copeptin ≥14 pmol·L−1 p-value Subjects n 268 134 134 Male 128 (47.8) 58 (43.3) 70 (52.2) 0.178 Age years 70.5 (53–77) 62.5 (46–74) 72.5 (64–79) <0.001 BMI kg·m−2 27.8 (24.8–31.2) 28.0 (25.0–32.1) 27.6 (24.5–30.6) 0.300 Risk factors for VTE History of VTE 85/267 (31.8) 50/133 (37.6) 35 (26.1) 0.049 Previous trauma/surgery# 55 (20.5) 28 (20.9) 27 (20.1) 1.000 Travel/immobilisation# 67 (25.0) 31 (23.1) 36 (26.9) 0.573 Pregnancy/post-partum¶ 1 (0.4) 1 (0.7) 0 (0) 1.000 Unprovoked PE+ 160 (59.7) 78 (58.2) 82 (61.2) 0.709 Comorbidities Malignant tumour§ 37 (13.8) 15 (11.2) 22 (16.4) 0.288 Chronic cardiopulmonary disease 93 (34.7) 35 (26.1) 58 (43.3) 0.005 Diabetes mellitus 49 (18.3) 15 (11.2) 34 (25.4) 0.004 Anaemia 91 (34.0) 41 (30.6) 50 (37.3) 0.302 Renal insufficiency 73 (27.2) 23 (17.2) 50 (37.3) <0.001 Symptoms and clinical status on admission Symptom onset <24 h 130 (48.5) 54 (40.3) 76 (56.7) 0.010 Chest pain 155/267 (58.1) 86/133 (64.7) 69 (51.5) 0.035 Dyspnoea 233/267 (87.3) 116/133 (87.2) 117 (87.3) 1.000 Syncope 32 (11.9) 7 (5.2) 25 (18.7) 0.001 Systolic blood pressure mmHg 130 (120–150) 130 (120–150) 130 (120–141) 0.017 Mild hypotension 19/262 (7.3) 6/130 (4.6) 13/132 (9.8) 0.152 Heart rate bpm 88 (74.25–105) 84 (75.5–97.5) 91 (73.5–110.0) 0.042 Tachycardia 80/264 (30.3) 31/132 (23.5) 49/132 (37.1) 0.022 Hypoxia 62/224 (27.7) 21/107 (19.6) 41/117 (35.0) 0.011 RV dysfunction on echocardiography 77/157 (49.0) 29/69 (42.0) 48/88 (54.5) 0.148 RV dysfunction on MDCT 111/255 (43.5) 45/130 (34.6) 66/125 (52.8) 0.004 Laboratory biomarkers hsTnT pg·mL−1 24.6 (8.6–57.9) 11.2 (4.9–43.8) 36.1 (15.1–73.7) <0.001 hsTnT ≥14 pg·mL−1 166/266 (62.4) 61/132 (46.2) 105/134 (78.4) <0.001 NT-proBNP pg·mL−1 687 (122–2564) 309 (74–1640) 1238 (290–3775) <0.001 NT-proBNP ≥600 pg·mL−1 138/267 (51.7) 55/134 (41.0) 83/133 (62.4) 0.001 Risk assessment models ESC 2014 algorithm Low 47 (17.5) 41 (30.6) 6 (4.5) <0.001 Intermediate–low 135 (50.4) 63 (47.0) 72 (53.7) 0.328 Intermediate–high 86 (32.1) 30 (22.4) 56 (41.8) 0.001 Bova scoreƒ Low 130 (48.7) 84 (62.7) 46 (34.6) <0.001 Intermediate–low 93 (34.8) 41 (30.6) 52 (39.1) 0.159 Intermediate–high 44 (16.5) 9 (6.7) 35 (26.3) <0.001 Data are presented as n, n (%), median (interquartile range) or n/N (%), unless otherwise stated. Risk factors, comorbidities, symptoms, haemodynamics, laboratory values and PE severity classification in all study patients and according to the median copeptin level are presented. BMI: body mass index; VTE: venous thromboembolism; PE: pulmonary embolism; bpm: beats per minute; RV: right ventricular; MDCT: multidetector computed tomography; hsTnT: high-sensitivity troponin T; NT-proBNP: N-terminal pro-brain natriuretic peptide; ESC: European Society of Cardiology. #: within the past 4 weeks; ¶: 6 weeks after delivery; +: defined as absence of a temporary or reversible risk factor such as surgery, trauma, immobilisation, travel, contraception/hormone replacement therapy or pregnancy; §: defined as active or under treatment within the past 6 months; ƒ: one patient could not be classified using the Bova score due to missing data. Definitions are provided in the material and methods section of the online supplementary material.
- TABLE 2
Prognostic performances of laboratory biomarkers and risk assessment models with regard to an adverse 30-day outcome
Sensitivity (95% CI) Specificity (95% CI) PPV (95% CI) NPV (95% CI) LR+ (95% CI) LR− (95% CI) Laboratory biomarker hsTnT ≥14 pg·mL−1 1.00 (0.80–1.00) 0.40 (0.34–0.46) 0.09 (0.06–0.14) 1.00 (0.96–1.00) 1.67 (1.50–1.84) NT-proBNP ≥600 pg·mL−1 1.00 (0.80–1.00) 0.51 (0.45–0.57) 0.11 (0.07–0.17) 1.00 (0.97–1.00) 1.96 (1.80–2.32) Copeptin ≥24 pmol·L−1 0.73 (0.48–0.89) 0.66 (0.60–0.72) 0.11 (0.07–0.19) 0.98 (0.94–0.99) 2.18 (1.54–3.10) 0.40 (0.17–0.93) Copeptin ≥24 pmol·L−1 and hsTnT ≥14 pg·mL−1 and NT-proBNP ≥600 pg·mL−1 0.73 (0.48–0.89) 0.83 (0.77–0.87) 0.20 (0.12–0.32) 0.98 (0.95–0.99) 4.25 (2.80–6.30) 0.32 (0.14–0.75) Risk assessment models ESC 2014 algorithm (intermediate–high risk versus low risk/intermediate–low risk) 0.67 (0.42–0.85) 0.70 (0.64–0.75) 0.12 (0.06–0.20) 0.97 (0.94–0.99) 2.22 (1.48–3.32) 0.48 (0.23–0.98) Bova score (intermediate–high risk versus low risk/intermediate–low risk) 0.33 (0.15–0.58) 0.85 (0.80–0.88) 0.11 (0.05–0.24) 0.96 (0.92–0.98) 2.15 (1.00–4,66) 0.79 (0.55–1.13) Sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of dichotomised/dichotomous biomarkers, risk assessment models and combination of biomarkers with regard to an adverse 30-day outcome. PPV: positive predictive value; NPV: negative predictive value; LR+/−: positive/negative likelihood ratio; hsTnT: high-sensitivity troponin T; NT-proBNP: N-terminal pro-brain natriuretic peptide; ESC: European Society of Cardiology.
- TABLE 3
Predictors of an adverse 30-day outcome
OR (95% CI) p-value Comorbidities Malignant tumour 1.61 (0.43–6.00) 0.478 Chronic cardiopulmonary disease 1.70 (0.60–4.84) 0.321 Diabetes mellitus 3.26 (1.10–9.62) 0.033 Renal insufficiency 2.48 (0.87–7.10) 0.091 Symptoms and clinical status on admission Syncope 1.93 (0.51–7.25) 0.330 Hypoxia 3.85 (1.28–11.60) 0.017 Tachycardia 3.76 (1.29–10.95) 0.015 Mild hypotension 2.08 (0.43–9.99) 0.360 RV dysfunction on echocardiography or MDCT 2.91 (0.90–9.38) 0.074 Laboratory biomarkers hsTnT ≥14 pg·mL−1 OR not calculable NT-proBNP ≥600 pg·mL−1 OR not calculable Copeptin ≥24 pmol·L−1 5.44 (1.68–17.58) 0.005 Copeptin ≥24 pmol·L−1 and hsTnT ≥14 pg·mL−1 and NT-proBNP ≥600 pg·mL−1 13.00 (3.91–42.72) <0.001 Risk assessment models ESC 2014 algorithm (intermediate–high risk versus low risk/intermediate–low risk) 4.66 (1.54–14.09) 0.006 Bova score (intermediate–high risk versus low risk/intermediate–low risk) 2.73 (0.89–8.42) 0.080 Definitions are provided in the material and methods section of the online supplementary material. RV: right ventricular; MDCT: multidetector computed tomography; hsTnT: high-sensitivity troponin T; NT-proBNP: N-terminal pro-brain natriuretic peptide; ESC: European Society of Cardiology.
Supplementary material
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- Supplementary material - Supplementary text and table
