Intern Emerg Med (2015) 10:663–669 DOI 10.1007/s11739-015-1198-4
IM - ORIGINAL
Heart rate in pulmonary embolism Karsten Keller • Johannes Beule • Meike Coldewey Wolfgang Dippold • Jo¨rn Oliver Balzer
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Received: 8 November 2014 / Accepted: 16 January 2015 / Published online: 30 January 2015 Ó SIMI 2015
Abstract Heart rate is a rapidly available risk stratification parameter in acute pulmonary embolism (PE). We aimed to investigate the effectiveness of heart rate in predicting the outcome in acute PE. Data of 182 patients with acute PE were analysed retrospectively. Logistic regression models were calculated to investigate the associations between heart rate and in-hospital death, myocardial necrosis, PE status and presence of right ventricular dysfunction (RVD), respectively. ROC curve and cut-off values for heart rate predicting RVD as well as intermediate risk PE status in normotensive PE patients and for heart rate predicting inhospital death and myocardial necrosis in all PE patients were calculated. ROC analysis for heart rate predicting RVD and intermediate risk PE were 0.706 and 0.718, respectively, with cut-off value of 86 beats/min. Regression models K. Keller (&) M. Coldewey Department of Medicine II, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany e-mail: [email protected] K. Keller M. Coldewey Centrum for Thrombosis and Haemostasis, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany J. Beule W. Dippold Department of Medicine, St. Vincenz and Elisabeth Hospital Mainz (KKM), Mainz, Germany J. O. Balzer Department of Radiology and Nuclear Medicine, Katholisches Klinikum Mainz (KKM), Mainz, Germany J. O. Balzer Department of Diagnostic and Interventional Radiology, University Clinic, Johann Wolfgang Goethe-University Frankfurt/Main, Frankfurt, Germany
showed associations between heart rate [85 beats/min and both RVD (OR 4.871, 95 % CI 2.256–10.515, P = 0.000055) and intermediate risk PE (OR 5.244, 95 % CI 2.418–11.377, P = 0.000027). In hemodynamically stable and unstable PE patients, logistic regression models showed a borderline significant association between tachycardia and in-hospital death (OR 7.066, 95 % CI 0.764–65.292, P = 0.0849) and a significant association between heart rate and myocardial necrosis (OR 0.975, 95 % CI 0.959–0.991, P = 0.00203). ROC analysis for heart rate predicting in-hospital death and myocardial necrosis revealed AUC of 0.655 and 0.703 with heart rate cut-off values of 99.5 beats/min and 92.5 beats/min, respectively. An elevated heart rate in acute PE is connected with a worse outcome. Effectiveness in the prediction of RVD, intermediate PE status, cardiac injury and in-hospital death is acceptable. The cut-off value for the prediction of RVD and intermediate risk PE status in normotensive PE is 86 beats/min, while tachycardia predicts in-hospital death. Keywords Pulmonary embolism Venous thromboembolism Heart rate Tachycardia Systolic pulmonary artery pressure
Introduction Pulmonary embolism (PE) is a potential life-threatening cardiovascular emergency with high morbidity and mortality [1–10]. The outcome of an acute PE event is closely connected to the initial hemodynamic status of the patients and the provoked cardiac adaptations [2–4, 7, 8, 11–17, 19]. Hemodynamically unstable PE patients have the highest mortality risk. Normotensive PE patients (75 % of the PE patients), reveal a better outcome than hemodynamically
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unstable PE patients. Normotensive PE patients with right ventricular dysfunction (RVD) or elevated levels of cardiac biomarkers (such as elevated cardiac Troponin (cTn) or BNP), have a higher mortality risk than those without [2–4, 6–8, 11–18, 20–22]. The heart rate is one further important parameter in risk stratification of an acute PE [8, 23–25]. The objectives of this study were to investigate heart rate cut-off values for the prediction of in-hospital death as well as myocardial necrosis in all included PE patients (both hemodynamically stable and instable PE patients), and intermediate risk PE status as well as right ventricular dysfunction (RVD) in normotensive PE patients. We aimed to ascertain which heart rate cut-off value is the best for risk stratification in acute normotensive PE to detect an intermediate risk PE status and RVD as well as to predict an in-hospital death and myocardial injury in acute PE patients overall.
of the ESC guidelines [8] and AHA scientific statement, [26] and for exact classification by reference to echocardiographic characteristics of RVD, if an accurate echocardiography examination of the acute phase existed. PE severity status PE status was defined according to the ESC guidelines and AHA scientific statement [8, 26]. Hemodynamically unstable PE patients were classified as high-risk PE patients. Normotensive PE patients with RVD or elevated levels of cardiac biomarkers such as elevated cTnI, were categorized as intermediate risk PE patients. Normotensive PE patients without both were included in the low-risk PE group (without RVD and normal biomarker levels) [2–4, 6–8, 11–18, 20–22]. Definition of RVD
Methods We performed a retrospective analysis of the patients with a confirmed diagnosis of acute PE, who were treated in the Internal Medicine department between May 2006 and June 2011. We identified the PE patients with a search of the hospital information system database for the diagnostic code of PE (ICD-Code: I26).
RVD was defined according to the AHA scientific statement from 2011 [26] as enlarged right ventricle seen as right ventricular (RV) septal-lateral diameter in 4 chamber view divided by left ventricular septal-lateral diameter [0.9, RV hypokinesis and tricuspid regurgitation in transthoracic echocardiography [26]. Definition of cardiac injury
Enrolled subjects Patients were eligible for this study 1.
2. 3.
If the diagnosis of an acute PE was confirmed by an identified filling defect in the pulmonary artery system in a computed tomography pulmonary angiogram (CTA) of the chest or positive venous ultrasound/ phlebography of an extremity consistent with DVT in patients with typical symptoms of PE (chest pain or dyspnea), and a detected positive D-Dimer or scintigraphic ventilation–perfusion (V/Q) scan read as high probability for PE; If the PE patients were treated in the Internal Medicine department of the hospital, and If the patients were 18 years or older.
All CTA or scintigraphic images were analysed by experienced radiologists. If the diagnosis of PE was not confirmed by the criteria above, patients were not included in this study. Definitions Normotensive PE patients PE patients were included in this subgroup, if systolic blood pressure was C90 mmHg according to the definition
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Myocardial necrosis was defined as cTnI elevation [0.1 ng/ml. Study parameters The retrospective analysis of the PE patients focused on heart rate, echocardiographic signs of RVD, cardiac biomarkers and in-hospital death. Statistics The PE patients with and without tachycardia were compared with Wilcoxon–Mann–Whitney U test. We performed logistic regression models to investigate the association between several heart rate cut-off values with RVD in normotensive PE. Moreover, we calculated a ROC analysis with area under the curve and heart rate cutoff point for prediction of RVD as well as intermediate risk PE status in normotensive PE patients. A logistic regression model was performed to investigate the association between the optimal heart rate cut-off for prediction of intermediate risk PE and the intermediate risk PE status in normotensive PE patients. We computed a ROC analysis with area under the curve and heart rate cut-off point for prediction of in-hospital
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death as well as myocardial necrosis in all PE patients of our study (both hemodynamically stable and instable PE patients). A logistic regression model was calculated to investigate the association between the optimal heart rate cut-off for prediction of in-hospital death and in-hospital death as well as between the optimal heart rate cut-off for prediction of myocardial necrosis and myocardial necrosis in PE patients. Commercially available software BIASÒ (version 10.04) was used for the computerized analysis. P values of \0.05 were considered as statistically significant.
Results Between May 2006 and June 2011, 182 patients (61.5 % female, 38.5 % male), with acute and confirmed PE events were identified in the information system database of the hospital and included in the study. The PE patients’ mean age was 68.5 ± 15.3 years (female 70.8 ± 15.1 years; male 64.9 ± 15.0 years). A PE diagnosis was made in 156 patients (85.7 %) using CTA. In 19 patients, V/Q scan (10.4 %) led to the diagnosis, and in 7 patients (3.9 %), the diagnosis was made by positive venous ultrasound/phlebography of an extremity, which was consistent with DVT in patients with typical symptoms of PE (chest pain or dyspnoea), and a positive D-dimer level.
5 PE patients died an in-hospital death after the PE event. 7 PE patients (3.8 %) presented with a hemodynamic unstable PE (high-risk PE patients). Therefore, 175 PE patients (96.2 %) were hemodynamically stable and were classified as non-high risk PE patients; but only 129 (59.7 % women, 40.3 % men) of these 175 hemodynamically stable PE patients were taken for the analysis of the normotensive PE patients’ group. For this subgroup analysis, we aimed to use only exact classification of the hemodynamically stable PE patients by reference to echocardiographic characteristics of RVD not only by CTA characteristics. Therefore, only the hemodynamically stable PE patients with accurate echocardiography were included in this analysed normotensive PE subgroup. Hence, 46 patients of the 175 hemodynamically stable PE patients without accurate echocardiography of the acute phase were not included in this analysed subgroup. The patients’ characteristics are shown in Table 1. Patients with tachycardia died more frequently an in-hospital death (5.9 vs. 0.9 %, P = 0.046), revealed lower systolic blood pressures (136.0 ± 35.1 vs. 148.2 ± 25.6 mmHg, P = 0.022), had higher levels of cTnI (0.21 ± 0.32 vs. 0.12 ± 0.25 ng/ml, P = 0.00015), and higher percentage of myocardial necrosis (45.0 vs. 16.0 %, P = 0.000065), than PE patients with heart rate \100 beats/min (Table 1). The calculated ROC analysis for heart rate predicting inhospital death revealed an AUC of 0.655 with heart rate cut-
Table 1 Characteristics of the PE patients with heart rate C100 beats/min and those with heart rate \100 beats/min
PE patients with heart rate C100 beats/min (n = 68)
PE patients with heart \100 beats/min (n = 114)
P
Gender (women)
61.8 % (42)
61.4 % (70)
0.35
Age (years)
68.3 ± 14.2
68.6 ± 15.9
0.96
Surgery or trauma in the last 3 months before PE event
16.2 % (11)
19.3 % (22)
0.56
DVT or PE in patient‘s history
16.4 % (11)
28.3 % (32)
0.07
Cancer
25.0 % (17)
17.5 % (20)
0.22
DVT
66.2 % (45)
66.7 % (76)
0.94
In-hospital death
5.9 % (4)
0.9 % (1)
0.046
Chest pain
27.9 % (19)
36.0 % (41)
0.27
Dyspnoea Hemoptysis
86.8 % (59) 4.5 % (3)
78.1 % (89) 2.6 % (3)
0.15 0.50
Syncope or collapse
16.2 % (11)
7.9 % (9)
0.08
Comorbidities
Symptoms Continuous variables are described by mean values and standard deviation. Discrete variables are described through relative and absolute frequencies P value for difference was tested with Mann–Whitney U test Bold values are statistically significant (P \ 0.05)
Physical examination Systolic blood pressure (mmHg)
136.0 ± 35.1
148.2 ± 25.6
0.022
Diastolic blood pressure (mmHg)
77.5 ± 24.8
77.4 ± 15.8
0.99
Laboratory Cardiac troponin I (ng/ml)
0.21 ± 0.32
0.12 ± 0.25
0.00015
Myocardial necrosis (cTnI [0.1 ng/ml)
45.0 % (27)
16.0 % (16)
0.000065
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off value of 99.5 beats/min for all PE patients of this study. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 28.1, 76.1, 68.9, 80.0 and 63.8 %, respectively (Fig. 1). The ROC analysis for heart rate predicting myocardial necrosis (cTnI [0.1 ng/ml) shows an AUC of 0.703 with heart rate cut-off value of 92.5 beats/min for all PE patients of this study. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 31.7, 72.0, 65.6, 59.8 and 76.7 %, respectively (Fig. 2). The logistic regression model showed a borderline significance for the association between tachycardia and inhospital death (OR 7.066, 95 % CI 0.764–65.292, P = 0.0849), and a significant association between heart rate and myocardial necrosis (OR 0.975, 95 % CI 0.959–0.991, P = 0.00203). In the normotensive PE subgroup of the 129 PE patients, the median age was 70.0 years (60.7/81.0). A DVT was detected in 70.5 % of the patients. One of the PE patients died in the hospital (0.8 %). 55.0 % of the PE patients of the normotensive subgroup showed a RVD in transthoracic echocardiography, and 59.7 % an intermediate risk PE severity status. Calculated logistic regression models reveal an association between heart rate and RVD (OR 1.034, 95 % CI 1.013–1.055, P = 0.001115). The regression models show the strongest association between heart rate and RVD for a cut-off heart rate of 85.0 beats/min (OR 4.871, 95 % CI 2.256–10.515, P = 0.000055) (Table 2). The ROC analysis for heart rate predicting RVD reveals an area under the curve of 0.706, and a heart rate cut-off
Fig. 1 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting in-hospital death. Optimal cut-off point is 99.5 beats/min. AUC is calculated at 0.655
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value for predicting RVD of 86.0 beats/min. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 31.6, 71.0, 66.3, 62.1 and 74.6 %, respectively (Fig. 3). The ROC analysis for heart rate as a risk stratification marker to predict intermediate risk PE status in normotensive PE patients shows an area under the curve of 0.718 and a cut-off value of 86 beats/min. Heart rate values [86.0 beats/min indicate an intermediate risk PE status. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 30.3, 71.6, 68.1, 65.4 and 74.0 %, respectively (Fig. 4). The logistic regression model confirms a strong association between heart rate values above 85 beats/min and intermediate risk PE status (OR 5.244, 95 % CI 2.418–11.377, P = 0.000027).
Discussion Acute PE is a relatively common cardiovascular emergency connected with high morbidity and mortality [1, 3, 8, 27, 28]. Rapid and accurate risk stratification is very important for an adequate treatment of acute PE [3, 4, 8, 11, 29, 30]. The results of the PEITHO study show that intermediate risk PE patients might benefit from more aggressive treatment options such as fibrinolytic therapy, although with a concomitant higher risk of bleeding [30]. Heart rate is a rapidly available and reliable parameter. Thus, having it available for risk stratification would be useful. Heart rate elevation in acute PE is connected with more severe PE status and a worse outcome [8, 23–25].
Fig. 2 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting myocardial necrosis. Optimal cut-off point is 92.5 beats/min. AUC is calculated as 0.703
Intern Emerg Med (2015) 10:663–669 Table 2 Univariable logistic regression to investigate the association between several heart rate cut-off levels and RVD in normotensive PE patients
Bold values are statistically significant (P \ 0.05)
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Right ventricular dysfunction (RVD)
OR (95 % CI)
P value
Heart rate [70 beats/min
4.838 (1.471–15.924)
0.009453
Heart rate [75 beats/min
4.211 (1.739–10.194)
0.001443
Heart rate [80 beats/min
3.887 (1.749–8.636)
0.000865
Heart rate [85 beats/min
4.871 (2.256–10.515)
0.000055
Heart rate [90 beats/min
4.478 (2.111–9.506)
0.000094
Heart rate [95 beats/min
3.219 (1.542–6.720)
0.001853
Heart rate [100 beats/min
3.766 (1.729–8.210)
0.000845
Heart rate [105 beats/min
3.397 (1.384–8.333)
0.007574
Heart rate [110 beats/min
2.475 (0.946–6.468)
0.064698
Heart rate [115 beats/min
2.376 (0.787–7.174)
0.124790
Heart rate [120 beats/min
0.937 (0.629–1.395)
0.747931
Heart rate (respectively, 1 beat/min)
1.034 (1.013–1.055)
0.001115
Fig. 3 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting RVD. Optimal cut-off point is 86 beats/min. AUC is calculated as 0.706
Fig. 4 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting intermediate risk PE status. Optimal cut-off point is 86 beats/min. AUC is calculated at 0.718
Therefore, elevated heart rate values have been included in outcome scores as PESI as a risk stratification parameter [23].
The objective of this study was to investigate the effectiveness of heart rate in the prediction of outcome in acute PE. Our study confirms that heart rate elevation is strongly connected with worse outcome seen in higher percentages of in-hospital death, myocardial necrosis, RVD and intermediate risk PE status. A rise of heart rate of 1 beat/min leads to an increase of risk of RVD of 1.3 % in acute normotensive PE events. Our study reveals that a cut-off value of 86 beats/min should be used to discriminate between no RVD and RVD as well as low-risk and intermediate risk PE status in normotensive PE patients. Heart rate values above 85 beats/min are connected with 5.2times higher risk of intermediate risk PE status and 4.9times higher risk of RVD. In hemodynamically stable and unstable PE patients (all PE patients of our study), a cut-off value of 99.5 beats/min should be used to identify higher risk of in-hospital death in PE patients overall. Tachycardia is associated with 7-times higher risk of in-hospital death. The calculated cut-off values of our study for predicting outcome in acute PE are distinctly lower than the used cutoff in PESI [23] The PESI predicts the 30-day outcome of patients with pulmonary embolism [23]. A heart rate of C110 beats/min is one of the parameters of the PESI score [23]. In accordance with our study results, Wicki et al. [31] report a borderline significance for tachycardia in prediction of adverse outcome in acute PE [31]. In contrast, the study results of Meneveau et al. [32] do not confirm that a heart rate [100/min is an independent predictor of in-hospital death [32]. Grifoni et al. [33] report that heart rate is significantly higher in PE patients with RVD than in those without [32]. The results of our study point out that a lower heart rate cut-off value than that of PESI should be used for the risk stratification in acute PE.
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The effectiveness of the heart rate to predict in-hospital death, myocardial necrosis, PE stadium and presence of RVD is acceptable with AUC values of 0.655, 0.703, 0.706 and 0.718, respectively. Our calculated effectiveness values are in the same range with published AUC values of cTn for prediction of RVD, adverse outcome and in-hospital death. Henzler et al. [34] and Logeart et al. [35] report an AUC of 0.70 and 0.72, respectively, for cTnI predicting RVD [34, 35]. Janata et al. [36] report an AUC of 0.92 for predicting inhospital death through cTnT [36] and Kucher et al. [18] an AUC of 0.90 for cTnI in combination with echocardiography to predict adverse outcome [18].
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Conclusions Elevated heart rate in acute PE is connected with worse outcome. Effectiveness in the prediction of RVD, intermediate PE status, cardiac injury and in-hospital death is acceptable. The cut-off value for prediction of RVD and intermediate risk PE status in normotensive PE is 86 beats/ min, while tachycardia predicts in-hospital death. The great advantage of the risk stratification marker heart rate is the rapid availability in contrast to measured biomarkers or assessment of complex scores.
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Limitations The central limitations of this study are its single center design and the retrospective data assessment. Therefore, follow-up examinations are missing. Beside the outcome marker in-hospital death, several study results have already shown the connection between intermediate risk PE status as well as RVD and elevated mortality in the follow-up. Therefore, the surrogate parameters of intermediate risk PE and RVD are established, and are widely used risk stratification markers for the outcome of PE. Conflict of interest
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None.
References 17. 1. Chalikias GK, Tziakas DN, Stakos DA, Konstantinides SV (2010) Managment of acute pulmonary embolism: a contemporary risk-tailored approach. Hellenic J Cardiol 51:437–450 2. Hsu JT, Chu CM, Chang ST, Cheng HW, Cheng NJ, Ho WC, Chung CM (2006) Prognostic role of alveolar-arterial oxygen pressure difference in acute pulmonary embolism. Circ J Off J Jpn Circ Soc 70:1611–1616 3. Ohigashi H, Haraguchi G, Yoshikawa S, Sasaki T, Kimura S, Inagaki H, Hachiya H, Hirao K, Isobe M (2010) Comparison of biomarkers for predicting disease severity and long-term
123
18.
19.
respiratory prognosis in patients with acute pulmonary embolism. Int Heart J 51:416–420 Schellhaass A, Walther A, Konstantinides S, Bottiger BW (2010) The diagnosis and treatment of acute pulmonary embolism. Deutsches Arzteblatt Int 107:589–595 Konstantinides S, Goldhaber SZ (2012) Pulmonary embolism: risk assessment and management. Eur Heart J 33:3014–3022 Masotti L, Righini M, Vuilleumier N, Antonelli F, Landini G, Cappelli R, Ray P (2009) Prognostic stratification of acute pulmonary embolism: focus on clinical aspects, imaging, and biomarkers. Vasc Health Risk Manag 5:567–575 Keller K, Beule J, Schulz A, Dippold W (2013) Troponin I as risk stratification marker in acute pulmonary artery embolism. Phlebologie 42:261–269 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP (2008) Guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Heart J 29:2276–2315 Labyk A, Kalbarczyk A, Piaszczyk A, Kostrubiec M, Kaczynska A, Bochowicz A, Pruszczyk P (2007) [Pulmonary embolism: a difficult diagnostic problem]. Pol Arch Med Wewn 117:8–12 McRae S (2010) Pulmonary embolism. Aust Fam Physician 39:462–466 Goldhaber SZ (2008) Assessing the prognosis of acute pulmonary embolism: tricks of the trade. Chest 133:334–336 Giannitsis E, Muller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, Katus HA (2000) Independent prognostic value of cardiac troponin t in patients with confirmed pulmonary embolism. Circulation 102:211–217 Jimenez D, Uresandi F, Otero R, Lobo JL, Monreal M, Marti D, Zamora J, Muriel A, Aujesky D, Yusen RD (2009) Troponinbased risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. Chest 136:974–982 Jimenez D, Diaz G, Molina J, Marti D, Del Rey J, Garcia-Rull S, Escobar C, Vidal R, Sueiro A, Yusen RD (2008) Troponin i and risk stratification of patients with acute nonmassive pulmonary embolism. Eur Respir J Off J Eur Soc Clin Respir Physiol 31:847–853 Sanchez O, Trinquart L, Caille V, Couturaud F, Pacouret G, Meneveau N, Verschuren F, Roy PM, Parent F, Righini M, Perrier A, Lorut C, Tardy B, Benoit MO, Chatellier G, Meyer G (2010) Prognostic factors for pulmonary embolism: the prep study, a prospective multicenter cohort study. Am J Respir Crit Care Med 181:168–173 Wu AH, Jaffe AS, Apple FS, Jesse RL, Francis GL, Morrow DA, Newby LK, Ravkilde J, Tang WH, Christenson RH, Cannon CP, Storrow AB (2007) National academy of clinical biochemistry laboratory medicine practice guidelines: use of cardiac troponin and b-type natriuretic peptide or n-terminal prob-type natriuretic peptide for etiologies other than acute coronary syndromes and heart failure. Clin Chem 53:2086–2096 Haddad F, Doyle R, Murphy DJ, Hunt SA (2008) Right ventricular function in cardiovascular disease, part ii: pathophysiology, clinical importance, and management of right ventricular failure. Circulation 117:1717–1731 Kucher N, Wallmann D, Carone A, Windecker S, Meier B, Hess OM (2003) Incremental prognostic value of troponin i and echocardiography in patients with acute pulmonary embolism. Eur Heart J 24:1651–1656 Park JH, Park YS, Kim YJ, Lee IS, Kim JH, Lee JH, Choi SW, Jeong JO, Seong IW (2011) Differentiation between acute and chronic cor pulmonales with midventricular systolic strain of the
Intern Emerg Med (2015) 10:663–669
20.
21.
22.
23.
24.
25.
26.
27.
28.
right ventricle in the emergency department. Heart Vessels 26:435–439 Kucher N, Rossi E, De Rosa M, Goldhaber SZ (2005) Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm hg or higher. Arch Intern Med 165:1777–1781 Becattini C, Vedovati MC, Agnelli G (2007) Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 116:427–433 Kreit JW (2004) The impact of right ventricular dysfunction on the prognosis and therapy of normotensive patients with pulmonary embolism. Chest 125:1539–1545 Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, Roy PM, Fine MJ (2005) Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 172:1041–1046 Kucher N, Goldhaber SZ (2003) Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation 108:2191–2194 Galle C, Papazyan JP, Miron MJ, Slosman D, Bounameaux H, Perrier A (2001) Prediction of pulmonary embolism extent by clinical findings, d-dimer level and deep vein thrombosis shown by ultrasound. Thromb Haemost 86:1156–1160 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK (2011) Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the american heart association. Circulation 123:1788–1830 Hsu JT, Chu CM, Chang ST, Cheng HW, Cheng NJ, Chung CM (2006) Prognostic role of right ventricular dilatation and troponin i elevation in acute pulmonary embolism. Int Heart J 47:775–781 Sanchez O, Trinquart L, Colombet I, Durieux P, Huisman MV, Chatellier G, Meyer G (2008) Prognostic value of right ventricular dysfunction in patients with haemodynamically stable
669
29.
30.
31.
32.
33.
34.
35.
36.
pulmonary embolism: a systematic review. Eur Heart J 29:1569–1577 Mikulewicz M, Lewczuk J (2008) Importance of cardiac biomarkers in risk stratification in acute pulmonary embolism. Cardiol J 15:17–20 Meyer G, Vicaut E, Konstantinides SV (2014) Fibrinolysis for intermediate-risk pulmonary embolism. N Engl J Med 371:581–582 Wicki J, Perrier A, Perneger TV, Bounameaux H, Junod AF (2000) Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost 84:548–552 Meneveau N, Ming LP, Seronde MF, Mersin N, Schiele F, Caulfield F, Bernard Y, Bassand JP (2003) In-hospital and longterm outcome after sub-massive and massive pulmonary embolism submitted to thrombolytic therapy. Eur Heart J 24:1447–1454 Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G, Conti A, Agnelli G, Berni G (2000) Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation 101:2817–2822 Henzler T, Roeger S, Meyer M, Schoepf UJ, Nance JW Jr, Haghi D, Kaminski WE, Neumaier M, Schoenberg SO, Fink C (2012) Pulmonary embolism: CT signs and cardiac biomarkers for predicting right ventricular dysfunction. Eur Respir J Off J Eur Soc Clin Respir Physiol 39:919–926 Logeart D, Lecuyer L, Thabut G, Tabet JY, Tartiere JM, Chavelas C, Bonnin F, Stievenart JL, Solal AC (2007) Biomarkerbased strategy for screening right ventricular dysfunction in patients with non-massive pulmonary embolism. Intensive Care Med 33:286–292 Janata K, Holzer M, Laggner AN, Mullner M (2003) Cardiac troponin t in the severity assessment of patients with pulmonary embolism: Cohort study. BMJ 326:312–313
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Heart rate in pulmonary embolism Karsten Keller • Johannes Beule • Meike Coldewey Wolfgang Dippold • Jo¨rn Oliver Balzer
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Received: 8 November 2014 / Accepted: 16 January 2015 / Published online: 30 January 2015 Ó SIMI 2015
Abstract Heart rate is a rapidly available risk stratification parameter in acute pulmonary embolism (PE). We aimed to investigate the effectiveness of heart rate in predicting the outcome in acute PE. Data of 182 patients with acute PE were analysed retrospectively. Logistic regression models were calculated to investigate the associations between heart rate and in-hospital death, myocardial necrosis, PE status and presence of right ventricular dysfunction (RVD), respectively. ROC curve and cut-off values for heart rate predicting RVD as well as intermediate risk PE status in normotensive PE patients and for heart rate predicting inhospital death and myocardial necrosis in all PE patients were calculated. ROC analysis for heart rate predicting RVD and intermediate risk PE were 0.706 and 0.718, respectively, with cut-off value of 86 beats/min. Regression models K. Keller (&) M. Coldewey Department of Medicine II, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Langenbeckstr. 1, 55131 Mainz, Germany e-mail: [email protected] K. Keller M. Coldewey Centrum for Thrombosis and Haemostasis, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Mainz, Germany J. Beule W. Dippold Department of Medicine, St. Vincenz and Elisabeth Hospital Mainz (KKM), Mainz, Germany J. O. Balzer Department of Radiology and Nuclear Medicine, Katholisches Klinikum Mainz (KKM), Mainz, Germany J. O. Balzer Department of Diagnostic and Interventional Radiology, University Clinic, Johann Wolfgang Goethe-University Frankfurt/Main, Frankfurt, Germany
showed associations between heart rate [85 beats/min and both RVD (OR 4.871, 95 % CI 2.256–10.515, P = 0.000055) and intermediate risk PE (OR 5.244, 95 % CI 2.418–11.377, P = 0.000027). In hemodynamically stable and unstable PE patients, logistic regression models showed a borderline significant association between tachycardia and in-hospital death (OR 7.066, 95 % CI 0.764–65.292, P = 0.0849) and a significant association between heart rate and myocardial necrosis (OR 0.975, 95 % CI 0.959–0.991, P = 0.00203). ROC analysis for heart rate predicting in-hospital death and myocardial necrosis revealed AUC of 0.655 and 0.703 with heart rate cut-off values of 99.5 beats/min and 92.5 beats/min, respectively. An elevated heart rate in acute PE is connected with a worse outcome. Effectiveness in the prediction of RVD, intermediate PE status, cardiac injury and in-hospital death is acceptable. The cut-off value for the prediction of RVD and intermediate risk PE status in normotensive PE is 86 beats/min, while tachycardia predicts in-hospital death. Keywords Pulmonary embolism Venous thromboembolism Heart rate Tachycardia Systolic pulmonary artery pressure
Introduction Pulmonary embolism (PE) is a potential life-threatening cardiovascular emergency with high morbidity and mortality [1–10]. The outcome of an acute PE event is closely connected to the initial hemodynamic status of the patients and the provoked cardiac adaptations [2–4, 7, 8, 11–17, 19]. Hemodynamically unstable PE patients have the highest mortality risk. Normotensive PE patients (75 % of the PE patients), reveal a better outcome than hemodynamically
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unstable PE patients. Normotensive PE patients with right ventricular dysfunction (RVD) or elevated levels of cardiac biomarkers (such as elevated cardiac Troponin (cTn) or BNP), have a higher mortality risk than those without [2–4, 6–8, 11–18, 20–22]. The heart rate is one further important parameter in risk stratification of an acute PE [8, 23–25]. The objectives of this study were to investigate heart rate cut-off values for the prediction of in-hospital death as well as myocardial necrosis in all included PE patients (both hemodynamically stable and instable PE patients), and intermediate risk PE status as well as right ventricular dysfunction (RVD) in normotensive PE patients. We aimed to ascertain which heart rate cut-off value is the best for risk stratification in acute normotensive PE to detect an intermediate risk PE status and RVD as well as to predict an in-hospital death and myocardial injury in acute PE patients overall.
of the ESC guidelines [8] and AHA scientific statement, [26] and for exact classification by reference to echocardiographic characteristics of RVD, if an accurate echocardiography examination of the acute phase existed. PE severity status PE status was defined according to the ESC guidelines and AHA scientific statement [8, 26]. Hemodynamically unstable PE patients were classified as high-risk PE patients. Normotensive PE patients with RVD or elevated levels of cardiac biomarkers such as elevated cTnI, were categorized as intermediate risk PE patients. Normotensive PE patients without both were included in the low-risk PE group (without RVD and normal biomarker levels) [2–4, 6–8, 11–18, 20–22]. Definition of RVD
Methods We performed a retrospective analysis of the patients with a confirmed diagnosis of acute PE, who were treated in the Internal Medicine department between May 2006 and June 2011. We identified the PE patients with a search of the hospital information system database for the diagnostic code of PE (ICD-Code: I26).
RVD was defined according to the AHA scientific statement from 2011 [26] as enlarged right ventricle seen as right ventricular (RV) septal-lateral diameter in 4 chamber view divided by left ventricular septal-lateral diameter [0.9, RV hypokinesis and tricuspid regurgitation in transthoracic echocardiography [26]. Definition of cardiac injury
Enrolled subjects Patients were eligible for this study 1.
2. 3.
If the diagnosis of an acute PE was confirmed by an identified filling defect in the pulmonary artery system in a computed tomography pulmonary angiogram (CTA) of the chest or positive venous ultrasound/ phlebography of an extremity consistent with DVT in patients with typical symptoms of PE (chest pain or dyspnea), and a detected positive D-Dimer or scintigraphic ventilation–perfusion (V/Q) scan read as high probability for PE; If the PE patients were treated in the Internal Medicine department of the hospital, and If the patients were 18 years or older.
All CTA or scintigraphic images were analysed by experienced radiologists. If the diagnosis of PE was not confirmed by the criteria above, patients were not included in this study. Definitions Normotensive PE patients PE patients were included in this subgroup, if systolic blood pressure was C90 mmHg according to the definition
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Myocardial necrosis was defined as cTnI elevation [0.1 ng/ml. Study parameters The retrospective analysis of the PE patients focused on heart rate, echocardiographic signs of RVD, cardiac biomarkers and in-hospital death. Statistics The PE patients with and without tachycardia were compared with Wilcoxon–Mann–Whitney U test. We performed logistic regression models to investigate the association between several heart rate cut-off values with RVD in normotensive PE. Moreover, we calculated a ROC analysis with area under the curve and heart rate cutoff point for prediction of RVD as well as intermediate risk PE status in normotensive PE patients. A logistic regression model was performed to investigate the association between the optimal heart rate cut-off for prediction of intermediate risk PE and the intermediate risk PE status in normotensive PE patients. We computed a ROC analysis with area under the curve and heart rate cut-off point for prediction of in-hospital
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death as well as myocardial necrosis in all PE patients of our study (both hemodynamically stable and instable PE patients). A logistic regression model was calculated to investigate the association between the optimal heart rate cut-off for prediction of in-hospital death and in-hospital death as well as between the optimal heart rate cut-off for prediction of myocardial necrosis and myocardial necrosis in PE patients. Commercially available software BIASÒ (version 10.04) was used for the computerized analysis. P values of \0.05 were considered as statistically significant.
Results Between May 2006 and June 2011, 182 patients (61.5 % female, 38.5 % male), with acute and confirmed PE events were identified in the information system database of the hospital and included in the study. The PE patients’ mean age was 68.5 ± 15.3 years (female 70.8 ± 15.1 years; male 64.9 ± 15.0 years). A PE diagnosis was made in 156 patients (85.7 %) using CTA. In 19 patients, V/Q scan (10.4 %) led to the diagnosis, and in 7 patients (3.9 %), the diagnosis was made by positive venous ultrasound/phlebography of an extremity, which was consistent with DVT in patients with typical symptoms of PE (chest pain or dyspnoea), and a positive D-dimer level.
5 PE patients died an in-hospital death after the PE event. 7 PE patients (3.8 %) presented with a hemodynamic unstable PE (high-risk PE patients). Therefore, 175 PE patients (96.2 %) were hemodynamically stable and were classified as non-high risk PE patients; but only 129 (59.7 % women, 40.3 % men) of these 175 hemodynamically stable PE patients were taken for the analysis of the normotensive PE patients’ group. For this subgroup analysis, we aimed to use only exact classification of the hemodynamically stable PE patients by reference to echocardiographic characteristics of RVD not only by CTA characteristics. Therefore, only the hemodynamically stable PE patients with accurate echocardiography were included in this analysed normotensive PE subgroup. Hence, 46 patients of the 175 hemodynamically stable PE patients without accurate echocardiography of the acute phase were not included in this analysed subgroup. The patients’ characteristics are shown in Table 1. Patients with tachycardia died more frequently an in-hospital death (5.9 vs. 0.9 %, P = 0.046), revealed lower systolic blood pressures (136.0 ± 35.1 vs. 148.2 ± 25.6 mmHg, P = 0.022), had higher levels of cTnI (0.21 ± 0.32 vs. 0.12 ± 0.25 ng/ml, P = 0.00015), and higher percentage of myocardial necrosis (45.0 vs. 16.0 %, P = 0.000065), than PE patients with heart rate \100 beats/min (Table 1). The calculated ROC analysis for heart rate predicting inhospital death revealed an AUC of 0.655 with heart rate cut-
Table 1 Characteristics of the PE patients with heart rate C100 beats/min and those with heart rate \100 beats/min
PE patients with heart rate C100 beats/min (n = 68)
PE patients with heart \100 beats/min (n = 114)
P
Gender (women)
61.8 % (42)
61.4 % (70)
0.35
Age (years)
68.3 ± 14.2
68.6 ± 15.9
0.96
Surgery or trauma in the last 3 months before PE event
16.2 % (11)
19.3 % (22)
0.56
DVT or PE in patient‘s history
16.4 % (11)
28.3 % (32)
0.07
Cancer
25.0 % (17)
17.5 % (20)
0.22
DVT
66.2 % (45)
66.7 % (76)
0.94
In-hospital death
5.9 % (4)
0.9 % (1)
0.046
Chest pain
27.9 % (19)
36.0 % (41)
0.27
Dyspnoea Hemoptysis
86.8 % (59) 4.5 % (3)
78.1 % (89) 2.6 % (3)
0.15 0.50
Syncope or collapse
16.2 % (11)
7.9 % (9)
0.08
Comorbidities
Symptoms Continuous variables are described by mean values and standard deviation. Discrete variables are described through relative and absolute frequencies P value for difference was tested with Mann–Whitney U test Bold values are statistically significant (P \ 0.05)
Physical examination Systolic blood pressure (mmHg)
136.0 ± 35.1
148.2 ± 25.6
0.022
Diastolic blood pressure (mmHg)
77.5 ± 24.8
77.4 ± 15.8
0.99
Laboratory Cardiac troponin I (ng/ml)
0.21 ± 0.32
0.12 ± 0.25
0.00015
Myocardial necrosis (cTnI [0.1 ng/ml)
45.0 % (27)
16.0 % (16)
0.000065
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off value of 99.5 beats/min for all PE patients of this study. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 28.1, 76.1, 68.9, 80.0 and 63.8 %, respectively (Fig. 1). The ROC analysis for heart rate predicting myocardial necrosis (cTnI [0.1 ng/ml) shows an AUC of 0.703 with heart rate cut-off value of 92.5 beats/min for all PE patients of this study. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 31.7, 72.0, 65.6, 59.8 and 76.7 %, respectively (Fig. 2). The logistic regression model showed a borderline significance for the association between tachycardia and inhospital death (OR 7.066, 95 % CI 0.764–65.292, P = 0.0849), and a significant association between heart rate and myocardial necrosis (OR 0.975, 95 % CI 0.959–0.991, P = 0.00203). In the normotensive PE subgroup of the 129 PE patients, the median age was 70.0 years (60.7/81.0). A DVT was detected in 70.5 % of the patients. One of the PE patients died in the hospital (0.8 %). 55.0 % of the PE patients of the normotensive subgroup showed a RVD in transthoracic echocardiography, and 59.7 % an intermediate risk PE severity status. Calculated logistic regression models reveal an association between heart rate and RVD (OR 1.034, 95 % CI 1.013–1.055, P = 0.001115). The regression models show the strongest association between heart rate and RVD for a cut-off heart rate of 85.0 beats/min (OR 4.871, 95 % CI 2.256–10.515, P = 0.000055) (Table 2). The ROC analysis for heart rate predicting RVD reveals an area under the curve of 0.706, and a heart rate cut-off
Fig. 1 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting in-hospital death. Optimal cut-off point is 99.5 beats/min. AUC is calculated at 0.655
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value for predicting RVD of 86.0 beats/min. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 31.6, 71.0, 66.3, 62.1 and 74.6 %, respectively (Fig. 3). The ROC analysis for heart rate as a risk stratification marker to predict intermediate risk PE status in normotensive PE patients shows an area under the curve of 0.718 and a cut-off value of 86 beats/min. Heart rate values [86.0 beats/min indicate an intermediate risk PE status. The percentage of misclassification, sensitivity, specificity, positive and negative predictive values were calculated as 30.3, 71.6, 68.1, 65.4 and 74.0 %, respectively (Fig. 4). The logistic regression model confirms a strong association between heart rate values above 85 beats/min and intermediate risk PE status (OR 5.244, 95 % CI 2.418–11.377, P = 0.000027).
Discussion Acute PE is a relatively common cardiovascular emergency connected with high morbidity and mortality [1, 3, 8, 27, 28]. Rapid and accurate risk stratification is very important for an adequate treatment of acute PE [3, 4, 8, 11, 29, 30]. The results of the PEITHO study show that intermediate risk PE patients might benefit from more aggressive treatment options such as fibrinolytic therapy, although with a concomitant higher risk of bleeding [30]. Heart rate is a rapidly available and reliable parameter. Thus, having it available for risk stratification would be useful. Heart rate elevation in acute PE is connected with more severe PE status and a worse outcome [8, 23–25].
Fig. 2 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting myocardial necrosis. Optimal cut-off point is 92.5 beats/min. AUC is calculated as 0.703
Intern Emerg Med (2015) 10:663–669 Table 2 Univariable logistic regression to investigate the association between several heart rate cut-off levels and RVD in normotensive PE patients
Bold values are statistically significant (P \ 0.05)
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Right ventricular dysfunction (RVD)
OR (95 % CI)
P value
Heart rate [70 beats/min
4.838 (1.471–15.924)
0.009453
Heart rate [75 beats/min
4.211 (1.739–10.194)
0.001443
Heart rate [80 beats/min
3.887 (1.749–8.636)
0.000865
Heart rate [85 beats/min
4.871 (2.256–10.515)
0.000055
Heart rate [90 beats/min
4.478 (2.111–9.506)
0.000094
Heart rate [95 beats/min
3.219 (1.542–6.720)
0.001853
Heart rate [100 beats/min
3.766 (1.729–8.210)
0.000845
Heart rate [105 beats/min
3.397 (1.384–8.333)
0.007574
Heart rate [110 beats/min
2.475 (0.946–6.468)
0.064698
Heart rate [115 beats/min
2.376 (0.787–7.174)
0.124790
Heart rate [120 beats/min
0.937 (0.629–1.395)
0.747931
Heart rate (respectively, 1 beat/min)
1.034 (1.013–1.055)
0.001115
Fig. 3 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting RVD. Optimal cut-off point is 86 beats/min. AUC is calculated as 0.706
Fig. 4 ROC curve with calculated area under the curve and optimal cut-off point for heart rate value predicting intermediate risk PE status. Optimal cut-off point is 86 beats/min. AUC is calculated at 0.718
Therefore, elevated heart rate values have been included in outcome scores as PESI as a risk stratification parameter [23].
The objective of this study was to investigate the effectiveness of heart rate in the prediction of outcome in acute PE. Our study confirms that heart rate elevation is strongly connected with worse outcome seen in higher percentages of in-hospital death, myocardial necrosis, RVD and intermediate risk PE status. A rise of heart rate of 1 beat/min leads to an increase of risk of RVD of 1.3 % in acute normotensive PE events. Our study reveals that a cut-off value of 86 beats/min should be used to discriminate between no RVD and RVD as well as low-risk and intermediate risk PE status in normotensive PE patients. Heart rate values above 85 beats/min are connected with 5.2times higher risk of intermediate risk PE status and 4.9times higher risk of RVD. In hemodynamically stable and unstable PE patients (all PE patients of our study), a cut-off value of 99.5 beats/min should be used to identify higher risk of in-hospital death in PE patients overall. Tachycardia is associated with 7-times higher risk of in-hospital death. The calculated cut-off values of our study for predicting outcome in acute PE are distinctly lower than the used cutoff in PESI [23] The PESI predicts the 30-day outcome of patients with pulmonary embolism [23]. A heart rate of C110 beats/min is one of the parameters of the PESI score [23]. In accordance with our study results, Wicki et al. [31] report a borderline significance for tachycardia in prediction of adverse outcome in acute PE [31]. In contrast, the study results of Meneveau et al. [32] do not confirm that a heart rate [100/min is an independent predictor of in-hospital death [32]. Grifoni et al. [33] report that heart rate is significantly higher in PE patients with RVD than in those without [32]. The results of our study point out that a lower heart rate cut-off value than that of PESI should be used for the risk stratification in acute PE.
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The effectiveness of the heart rate to predict in-hospital death, myocardial necrosis, PE stadium and presence of RVD is acceptable with AUC values of 0.655, 0.703, 0.706 and 0.718, respectively. Our calculated effectiveness values are in the same range with published AUC values of cTn for prediction of RVD, adverse outcome and in-hospital death. Henzler et al. [34] and Logeart et al. [35] report an AUC of 0.70 and 0.72, respectively, for cTnI predicting RVD [34, 35]. Janata et al. [36] report an AUC of 0.92 for predicting inhospital death through cTnT [36] and Kucher et al. [18] an AUC of 0.90 for cTnI in combination with echocardiography to predict adverse outcome [18].
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5. 6.
7.
8.
Conclusions Elevated heart rate in acute PE is connected with worse outcome. Effectiveness in the prediction of RVD, intermediate PE status, cardiac injury and in-hospital death is acceptable. The cut-off value for prediction of RVD and intermediate risk PE status in normotensive PE is 86 beats/ min, while tachycardia predicts in-hospital death. The great advantage of the risk stratification marker heart rate is the rapid availability in contrast to measured biomarkers or assessment of complex scores.
9.
10. 11. 12.
13.
Limitations The central limitations of this study are its single center design and the retrospective data assessment. Therefore, follow-up examinations are missing. Beside the outcome marker in-hospital death, several study results have already shown the connection between intermediate risk PE status as well as RVD and elevated mortality in the follow-up. Therefore, the surrogate parameters of intermediate risk PE and RVD are established, and are widely used risk stratification markers for the outcome of PE. Conflict of interest
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16.
None.
References 17. 1. Chalikias GK, Tziakas DN, Stakos DA, Konstantinides SV (2010) Managment of acute pulmonary embolism: a contemporary risk-tailored approach. Hellenic J Cardiol 51:437–450 2. Hsu JT, Chu CM, Chang ST, Cheng HW, Cheng NJ, Ho WC, Chung CM (2006) Prognostic role of alveolar-arterial oxygen pressure difference in acute pulmonary embolism. Circ J Off J Jpn Circ Soc 70:1611–1616 3. Ohigashi H, Haraguchi G, Yoshikawa S, Sasaki T, Kimura S, Inagaki H, Hachiya H, Hirao K, Isobe M (2010) Comparison of biomarkers for predicting disease severity and long-term
123
18.
19.
respiratory prognosis in patients with acute pulmonary embolism. Int Heart J 51:416–420 Schellhaass A, Walther A, Konstantinides S, Bottiger BW (2010) The diagnosis and treatment of acute pulmonary embolism. Deutsches Arzteblatt Int 107:589–595 Konstantinides S, Goldhaber SZ (2012) Pulmonary embolism: risk assessment and management. Eur Heart J 33:3014–3022 Masotti L, Righini M, Vuilleumier N, Antonelli F, Landini G, Cappelli R, Ray P (2009) Prognostic stratification of acute pulmonary embolism: focus on clinical aspects, imaging, and biomarkers. Vasc Health Risk Manag 5:567–575 Keller K, Beule J, Schulz A, Dippold W (2013) Troponin I as risk stratification marker in acute pulmonary artery embolism. Phlebologie 42:261–269 Torbicki A, Perrier A, Konstantinides S, Agnelli G, Galie N, Pruszczyk P, Bengel F, Brady AJ, Ferreira D, Janssens U, Klepetko W, Mayer E, Remy-Jardin M, Bassand JP (2008) Guidelines on the diagnosis and management of acute pulmonary embolism: the task force for the diagnosis and management of acute pulmonary embolism of the European Society of Cardiology (ESC). Eur Heart J 29:2276–2315 Labyk A, Kalbarczyk A, Piaszczyk A, Kostrubiec M, Kaczynska A, Bochowicz A, Pruszczyk P (2007) [Pulmonary embolism: a difficult diagnostic problem]. Pol Arch Med Wewn 117:8–12 McRae S (2010) Pulmonary embolism. Aust Fam Physician 39:462–466 Goldhaber SZ (2008) Assessing the prognosis of acute pulmonary embolism: tricks of the trade. Chest 133:334–336 Giannitsis E, Muller-Bardorff M, Kurowski V, Weidtmann B, Wiegand U, Kampmann M, Katus HA (2000) Independent prognostic value of cardiac troponin t in patients with confirmed pulmonary embolism. Circulation 102:211–217 Jimenez D, Uresandi F, Otero R, Lobo JL, Monreal M, Marti D, Zamora J, Muriel A, Aujesky D, Yusen RD (2009) Troponinbased risk stratification of patients with acute nonmassive pulmonary embolism: systematic review and metaanalysis. Chest 136:974–982 Jimenez D, Diaz G, Molina J, Marti D, Del Rey J, Garcia-Rull S, Escobar C, Vidal R, Sueiro A, Yusen RD (2008) Troponin i and risk stratification of patients with acute nonmassive pulmonary embolism. Eur Respir J Off J Eur Soc Clin Respir Physiol 31:847–853 Sanchez O, Trinquart L, Caille V, Couturaud F, Pacouret G, Meneveau N, Verschuren F, Roy PM, Parent F, Righini M, Perrier A, Lorut C, Tardy B, Benoit MO, Chatellier G, Meyer G (2010) Prognostic factors for pulmonary embolism: the prep study, a prospective multicenter cohort study. Am J Respir Crit Care Med 181:168–173 Wu AH, Jaffe AS, Apple FS, Jesse RL, Francis GL, Morrow DA, Newby LK, Ravkilde J, Tang WH, Christenson RH, Cannon CP, Storrow AB (2007) National academy of clinical biochemistry laboratory medicine practice guidelines: use of cardiac troponin and b-type natriuretic peptide or n-terminal prob-type natriuretic peptide for etiologies other than acute coronary syndromes and heart failure. Clin Chem 53:2086–2096 Haddad F, Doyle R, Murphy DJ, Hunt SA (2008) Right ventricular function in cardiovascular disease, part ii: pathophysiology, clinical importance, and management of right ventricular failure. Circulation 117:1717–1731 Kucher N, Wallmann D, Carone A, Windecker S, Meier B, Hess OM (2003) Incremental prognostic value of troponin i and echocardiography in patients with acute pulmonary embolism. Eur Heart J 24:1651–1656 Park JH, Park YS, Kim YJ, Lee IS, Kim JH, Lee JH, Choi SW, Jeong JO, Seong IW (2011) Differentiation between acute and chronic cor pulmonales with midventricular systolic strain of the
Intern Emerg Med (2015) 10:663–669
20.
21.
22.
23.
24.
25.
26.
27.
28.
right ventricle in the emergency department. Heart Vessels 26:435–439 Kucher N, Rossi E, De Rosa M, Goldhaber SZ (2005) Prognostic role of echocardiography among patients with acute pulmonary embolism and a systolic arterial pressure of 90 mm hg or higher. Arch Intern Med 165:1777–1781 Becattini C, Vedovati MC, Agnelli G (2007) Prognostic value of troponins in acute pulmonary embolism: a meta-analysis. Circulation 116:427–433 Kreit JW (2004) The impact of right ventricular dysfunction on the prognosis and therapy of normotensive patients with pulmonary embolism. Chest 125:1539–1545 Aujesky D, Obrosky DS, Stone RA, Auble TE, Perrier A, Cornuz J, Roy PM, Fine MJ (2005) Derivation and validation of a prognostic model for pulmonary embolism. Am J Respir Crit Care Med 172:1041–1046 Kucher N, Goldhaber SZ (2003) Cardiac biomarkers for risk stratification of patients with acute pulmonary embolism. Circulation 108:2191–2194 Galle C, Papazyan JP, Miron MJ, Slosman D, Bounameaux H, Perrier A (2001) Prediction of pulmonary embolism extent by clinical findings, d-dimer level and deep vein thrombosis shown by ultrasound. Thromb Haemost 86:1156–1160 Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK (2011) Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the american heart association. Circulation 123:1788–1830 Hsu JT, Chu CM, Chang ST, Cheng HW, Cheng NJ, Chung CM (2006) Prognostic role of right ventricular dilatation and troponin i elevation in acute pulmonary embolism. Int Heart J 47:775–781 Sanchez O, Trinquart L, Colombet I, Durieux P, Huisman MV, Chatellier G, Meyer G (2008) Prognostic value of right ventricular dysfunction in patients with haemodynamically stable
669
29.
30.
31.
32.
33.
34.
35.
36.
pulmonary embolism: a systematic review. Eur Heart J 29:1569–1577 Mikulewicz M, Lewczuk J (2008) Importance of cardiac biomarkers in risk stratification in acute pulmonary embolism. Cardiol J 15:17–20 Meyer G, Vicaut E, Konstantinides SV (2014) Fibrinolysis for intermediate-risk pulmonary embolism. N Engl J Med 371:581–582 Wicki J, Perrier A, Perneger TV, Bounameaux H, Junod AF (2000) Predicting adverse outcome in patients with acute pulmonary embolism: a risk score. Thromb Haemost 84:548–552 Meneveau N, Ming LP, Seronde MF, Mersin N, Schiele F, Caulfield F, Bernard Y, Bassand JP (2003) In-hospital and longterm outcome after sub-massive and massive pulmonary embolism submitted to thrombolytic therapy. Eur Heart J 24:1447–1454 Grifoni S, Olivotto I, Cecchini P, Pieralli F, Camaiti A, Santoro G, Conti A, Agnelli G, Berni G (2000) Short-term clinical outcome of patients with acute pulmonary embolism, normal blood pressure, and echocardiographic right ventricular dysfunction. Circulation 101:2817–2822 Henzler T, Roeger S, Meyer M, Schoepf UJ, Nance JW Jr, Haghi D, Kaminski WE, Neumaier M, Schoenberg SO, Fink C (2012) Pulmonary embolism: CT signs and cardiac biomarkers for predicting right ventricular dysfunction. Eur Respir J Off J Eur Soc Clin Respir Physiol 39:919–926 Logeart D, Lecuyer L, Thabut G, Tabet JY, Tartiere JM, Chavelas C, Bonnin F, Stievenart JL, Solal AC (2007) Biomarkerbased strategy for screening right ventricular dysfunction in patients with non-massive pulmonary embolism. Intensive Care Med 33:286–292 Janata K, Holzer M, Laggner AN, Mullner M (2003) Cardiac troponin t in the severity assessment of patients with pulmonary embolism: Cohort study. BMJ 326:312–313
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