Midregional proadrenomedullin (MR-proADM) in the risk stratification of patients with acute pulmonary embolism.

INTRODUCTION: According to current ESC guidelines not only hemodynamic parameters, but also indices of right ventricular dysfunction such as NT-proBNP have a significant prognostic value in acute pulmonary embolism (PE). MR-proADM is a significant predictor of short-term mortality in acute heart failure and adds prognostic value to NT-proBNP. We hypothesized that plasma MR-proADM is elevated in acute PE, correlates with the severity of PE and has prognostic value. We also compared prognostic values of MR-proADM and NT-proBNP for the prediction of early mortality in acute PE. MATERIAL & METHODS: We studied 98 patients (51F/47M, 59.6 ± 18.4 yr) with acute PE. On admission blood samples were collected for MR-proADM and NT-proBNP. RESULTS: MR-proADM reflected the severity of acute PE: 0.734 nmol/L in low-risk acute PE (0.384-1.342), 0.995 nmol/L in intermediate-risk acute PE (0.394-7.499) and 2.062 nmol/L in high-risk acute PE (0.447-3.098), p<0.001. MR-proADM was higher in non-survivors than in survivors 2.123 nmol/L (1.543-4.220), vs. 0.910 nmol/L (0.384-7.449), p=0.0003. The AUC of MR-proADM and NT-proBNP ROC curves for predicting all-cause mortality were 0.935 (95% CI 0.861-0.977) and 0.844 (95% CI 0.749-0. 913), respectively. In univariable analysis NT-proBNP and MR-proADM were significant predictors of all-cause mortality HR 1.00 (95% CI 1.000-1.0002, p=0.029) and 1.65 (95% CI 1.214 - 2.249, p=0.015). However, in multivariate analysis, MR-proADM but not NT-proBNP was a significant predictor of all-cause mortality. CONCLUSION: NT-proBNP and MR-proADM are of similar predictive value in the assessment of outcome in acute PE, however MR-proADM seems to be superior in predicting all-cause mortality.

Rapid improvement of renal function in patients with acute pulmonary embolism indicates favorable short term prognosis.

OBJECTIVE: Various clinical and biochemical parameters predict the prognosis of patients with acute pulmonary embolism(APE). Treatment of APE can improve a patient's hemodynamic status, restoring adequate peripheral organ perfusion. Therefore, we hypothesized that improvement of renal function can predict short term prognosis of APE patients. MATERIAL & METHOD: We evaluated 232 consecutive patients (94 men,aged 67 ± 18 years) with APE proven by spiral computer tomography. Blood samples were collected for creatinine assays on admission and 72 hours later, the glomerular filtration rate(eGFR) was estimated using the MDRD formula. RESULTS: During the first 72 hours, 6 subjects died, while during the first 30 days 24(10%) subjects died (APE mortality 8%). On admission eGFR<60 ml/min was present in 113 patients(49%) and after 72 hours in 85 patients(38%). In 26 patients(11%) eGFR on admission was <60 ml/min and renal function did not improve during subsequent 72 hours. In this group the 30-day all-cause and APE-related mortality rates were 27% and 23%, respectively, while serious adverse events occurred in 38% of them. 206 patients with eGFR>60 ml/min showed a more favorable prognosis (8% 30-day all-cause mortality) than subjects with eGFR<60 ml/min and a stable eGFR during the first 72 hours (27% mortality rate, p<0.003). Persistent renal dysfunction predicted all-cause and PE-related 30-day mortality (hazard risk 2.53(CI 95%:0.96-6.68),p=0.06 and 3.04(CI 95%:1.28-7.26),p=0.01, respectively). CONCLUSION: Approximately 50% of patients with APE have at least a moderately impaired renal function on admission. Renal function improves within 72 hours in patients with a good prognosis, while "persistent" renal dysfunction indicates an increased mortality.

Neutrophil gelatinase-associated lipocalin, cystatin C and eGFR indicate acute kidney injury and predict prognosis of patients with acute pulmonary embolism.

OBJECTIVE: Risk stratification in acute pulmonary embolism (APE) includes the assessment of clinical status, right ventricular dysfunction and troponin concentrations. Since acute renal impairment is one of the important predictors of mortality in cardiovascular diseases, the authors hypothesised that it is an independent mortality marker in APE. MATERIAL AND METHODS: The authors observed 142 consecutive patients (52 M/90 F, 64±18 years) with APE diagnosed with contrast enhanced multislice CT. On admission, blood samples were collected for neutrophil gelatinase-associated lipocalin (N-GAL), cystatin C and creatinine assays. Estimated glomerular filtration rate (eGFR) was calculated using MDRD formula. RESULTS: Fourteen (10%) of 142 patients died by the 30th day of observation. eGFR≤60 ml/min was noted in 68 (48%) patients and eGFR≤30 ml/min in 11 (8%) patients. eGFR was higher in survivors than in non-survivors (66 (17-169) vs 46 (10-119) ml/min, respectively, p=0.02). In 80 (56%) patients, N-GAL was >50 ng/ml indicating acute kidney injury. N-GAL was higher in non-survivors than in survivors (88.8 (28.4-200.0) vs 53.0 (7.1-200.0) ng/ml, p<0.01). N-GAL level >50 ng/ml was found in 11 (79%) patients with fatal outcome. Area under the curve of N-GAL for all-cause mortality in ROC analysis was 0.715. N-GAL>75 ng/ml was present in 44 (31%) patients, while cystatin C >1900 ng/ml in 14 (10%) subjects. They showed sensitivity, specificity, positive predictive value and negative predictive value for prediction of all-cause death ((64%, 73%, 21%, 95%) and (36%, 91%, 30% 93%), respectively). N-GAL>75 ng/ml and cystatin C>1900 ng/ml increased the risk of death (HR 4.4 (95% CI 1.48 to 13.2, p<0.01) and 4.7 (95% CI 1.56 to 13.9, p=0.01), respectively). CONCLUSIONS: Acute kidney injury assessed by N-GAL occurs in 30% of APE and may contribute to the impairment of renal function present in half of them. Moreover, N-GAL, cystatin C elevation and low eGFR are associated with a poor 30-day prognosis in APE.

Acute pulmonary embolism: analysis of consecutive 353 patients hospitalised in a single centre. A 3-year experience.

BACKGROUND AND AIM: Despite significant progress on the diagnosis work-up of patients with suspented acute pulmonary embolism (APE), several therapeutic and prognostic issues have not yet been well established. METHODS: We analysed the clinical course of 353 consecutive patients (141 males, 212 females, mean age 64.7 ± 18.12 years) with APE confirmed by contrast-enhanced multidetector computed tomography who were diagnosed and treated in a reference hospital between 2007 and 2009. RESULTS: Among patients with APE, groups with high (HR), intermediate (IR) and low (LR) risk of early mortality were defined according to the recent European Society of Cardiology guidelines. High, intermediate and low risk groups included 23 patients (10 M, 13 F, age 70.13 ± 16.95 years), 146 patients (61 M, 85 F, age 65.77 ± 17.74 years), and 184 patients (70 M, 114 F, age 63.17 ± 18.45 years), respectively. Majority of patients (91.8%) were anticoagulated only with unfractionated or low-molecular-weight heparin, and thrombolysis was used in 24 patients, including 39.1% of HR patients, 8.9% of IR patients, and 1% of LR patients. In-hospital mortality rate was 7% overall (including 5.4% APE-related), 65.2% in HR (43.5% APE-related), 6.2% in IR (4.1% APE-related) and 2.2% in LR (1.63% APE-related). However, 4 of 9 high risk patients treated with thrombolysis died (mortality rate 44.4%), while mortality among HR patients not treated with thrombolysis reached 73.3%. Potential contraindications were taken into account before the decision to initiate thrombolysis. End-stage neoplasm or recent major surgery were considered contraindications for thrombolysis. Strong prognostic factors of overall in-hospital mortality included age (odd ratio [OR] 1.07, 95% confidence interval [CI] 1.02-1.12), heart rate (OR 1.04, 95% CI 1.02-1.06), and plasma creatinine level (OR 3.65, 95% CI 1.62-8.27), the latter also being a significant prognostic factor of mortality in low risk group (OR 3.9, 95% CI 1.6-9.8). NT-proBNP and troponin I plasma levels were also significant prognostic factors of in-hospital mortality (NT-proBNP: OR 5.91, 95% CI 2.38-14.65, p < 0.05; troponin I (cut-off value ≥ 0.1 µg/L): OR 2.77, 95% CI 0.97-7.93, p = 0.056). In the overall study population and also in non-high risk group, significant predictors of a combined endpoint (death, shock, intubation, catecholamines, and thrombolysis) were: age, heart rate, creatinine, troponin I, NT-proBNP, and tricuspid pressure gradient. CONCLUSIONS: Despite adequate treatment there is a possibility of haemodynamic collapse and the need for thrombolysis in approximately 9% of intermediate risk APE patients. Not only age and compromised haemodynamic status but also plasma creatinine, NT-proBNP, and troponin I levels are prognostic factors of early in-hospital mortality in patients with APE. Due to high mortality rate among non-thrombolysed high risk patients, their therapy should be more aggressive and contraindications for thrombolysis should be less restrictive.

Electrocardiographic differentiation between acute pulmonary embolism and non-ST elevation acute coronary syndromes at the bedside.

BACKGROUND: Clinical picture of acute pulmonary embolism (APE), with wide range of electrocardiographic (ECG) abnormalities can mimic acute coronary syndromes. OBJECTIVES: Assessment of standard 12-lead ECG usefulness in differentiation at the bedside between APE and non-ST elevation acute coronary syndrome (NSTE-ACS). METHODS: Retrospective analysis of 143 patients: 98 consecutive patients (mean age 63.4 +/- 19.4 year, 45 M) with APE and 45 consecutive patients (mean age 72.8 +/- 10.8 year, 44 M) with NSTE-ACS. Standard ECGs recorded on admission were compared in separated groups. RESULTS: Right bundle branch block (RBBB) and S(1)S(2)S(3) or S(1)Q(3)T(3) pattern were found in similar frequency in both groups (10 [11%] APE patients vs 6 [14%] NSTE-ACS patients, 27 [28%] patients vs 7 [16%] patients, respectively, NS). Negative T waves in leads V(1-3) together with negative T waves in inferior wall leads II, III, aVF (OR 1.3 [1.14-1.68]) significantly indicated APE with a positive predictive value of 85% and specificity of 87%. However, counterclockwise axis rotation (OR 4.57 [2.74-7.61]), ventricular premature beats (OR 2.60 [1.60-4.19]), ST depression in leads V(1-3) (OR 2.25 [1.43-3.56]), and negative T waves in leads V(5-6) (OR 2.08 [1.31-3.29]) significantly predicted NSTE-ACS. CONCLUSIONS: RBBB, S(1)S(2)S(3), or S(1)Q(3)T(3) pattern described as characteristic for APE were not helpful in the differentiation between APE and NSTE-ACS in studied group. Coexistence of negative T waves in precordial leads V(1-3) and inferior wall leads may suggest APE diagnosis.

Signs of myocardial ischemia on electrocardiogram correlate with elevated plasma cardiac troponin and right ventricular systolic dysfunction in acute pulmonary embolism.

BACKGROUND: Plasma cardiac troponins (cTn) are frequently elevated in acute pulmonary embolism (APE). ST-segment abnormalities on electrocardiography are also commonly observed in APE patients. However, it has not been defined which ventricle is a potential source of cTn release. We assessed the potential relationship between electrocardiographic signs of myocardial ischemia, systolic dysfunction of both ventricles at echocardiography and cTn levels in APE. METHODS: We evaluated 94 consecutive patients (42 male, 52 female, aged 63 +/- 19 years) with APE. On admission, blood samples were collected for cTnI or cTnT and standard 12-lead electrocardiogram was performed. The following signs of myocardial ischemia were analyzed: T-wave inversion [T (-)] and ST-depression or elevation (> or = 1 mV, at > or = 2 leads). The assessment of systolic function of both ventricles was performed by echocardiography. RESULTS: In 33 (35%) patients, cTn exceeded the upper reference limit of our laboratory. The history of coronary artery disease (27% vs. 31%) and previous myocardial infarction (12% vs. 10%) did not differ in patients with elevated cTn [cTn (+)] and non-elevated cTn [cTn (-)]. In cTn (+) group T (-) or ST-depression were observed more frequently than in cTn (-) [32 (97%) vs. 46 (75%), p < 0.01]. However, both groups presented similar frequency of ST-elevation [7 (21%) vs. 11 (18%), p = NS). Interestingly, cTn levels correlated with the number of leads with T (-) or ST-depression (R = 0.30, p < 0.01). Moreover, in cTn (+) group right ventricular systolic dysfunction was more frequent [15 (54%) vs. 4 (7%), p = 0.0001], while left ventricle contractility abnormalities occurred similarly in both groups [3 (11%) vs. 8 (15%), p = NS]. CONCLUSIONS: Signs of myocardial ischemia (ST-segment changes) on electrocardiography in APE correlate with an elevated cTn and with the impairment of right, but not left, ventricle systolic function at echocardiography.

Mean platelet volume predicts early death in acute pulmonary embolism.

BACKGROUND: Recently, mean platelet volume (MPV) was reported to predict venous thromboembolism. Moreover, MPV correlates with platelet reactivity and indicates poor outcome in acute coronary syndromes. OBJECTIVE: To examine the hypothesis that in acute pulmonary embolism (APE) MPV is elevated and may predict mortality. METHODS AND RESULTS: The study included consecutive 192 patients with APE, (79M/113F, 64+/-18 years) and 100 controls matched for age, sex and concomitant diseases. On admission blood samples were collected for MPV and troponin measurements. Although MPV did not differ between patients with APE and controls (10.0+/-1.2 vs 10.1+/-0.8 fl), it differed between low- and intermediate- or high-risk APE (9.4+/-1.2 fl, 10.3+/-1.1 fl, 10.3+/-1.8 fl; respectively, p<0.0001). Eighteen (9%) patients with APE died during the 30-day observation. MPV was higher in non-survivors than survivors (10.7+/-1.4 fl vs 9.9+/-1.2fl, p<0.01). The areas under receiver operating characteristic curves of MPV were 0.658 (95% CI 0.587 to 0.725) for predicting 30-day mortality, and 0.712 (95% CI 0.642 to 0.775) for 7-day mortality. MPV >10.9 fl, showed sensitivity, specificity, positive predictive value and negative predictive value for death within 30 days (39%, 81%, 18%, 93%, respectively) and for 7-day mortality (54%, 82%, 18%, 96%). Multivariable analysis showed that MPV was an independent mortality predictor for 7- and 30-day all-cause mortality (HR=2.0 (95% CI 1.3 to 3.0), p<0.001)) and 1.7 (95% CI 1.2 to 2.5), p<0.01)), respectively). MPVs were higher in patients with myocardial injury than in those without troponin elevation (10.2+/-1.1 fl vs 9.8+/-1.2 fl; p=0.02). There were correlations between MPV and right ventricular diameter and right ventricular dysfunction (r=0.28, p<0.01 and r=0.19, p<0.02, respectively). CONCLUSION: MPV is an independent predictor of early death in APE. Moreover, MPV in APE is associated with right ventricular dysfunction and myocardial injury.

Is it possible to use standard electrocardiography for risk assessment of patients with pulmonary embolism?

BACKGROUND: Risk stratification of patients with acute pulmonary embolism (APE) is crucial for appropriate treatment selection. Shock and hypotonia are known indications for aggressive management. However, in the haemodynamically stable group the best prognosis strategy is still being sought. Acute pulmonary embolism often provokes changes in electrocardiography recordings (ECG). AIM: To assess whether ECG features recorded on admission can be useful for risk stratification during hospitalisation. METHODS: We analysed 12-lead ECG and echocardiography of 56 patients (22 males, age: 64.3 +/- 17.9 years) with diagnosed APE. The diagnosis of APE was confirmed by spiral computer tomography. The ECG analysis was based on the 21-point ECG score including: the presence of tachycardia (> 100 beats/min), right bundle branch block, negative S waves in lead I, negative Q or T waves in lead III, S1Q3T3 complex and depth of negative T waves in leads V1-V4. ECG features were scored from 0 to 21 points. Complicated in-hospital course was defined as need for vasopressor, thrombolysis, embolectomy or resuscitation and the presence of shock index > 1 (heart rate/systolic blood pressure). RESULTS: Four (7.1%) patients died during hospitalisation and in 8 (14.3%) others complications occurred. Patients with complications had higher mean sum of 21-ECG score compared to subjects with uneventful course [8 (1-17) vs. 3 (0-18); p = 0.04]. Right ventricular contractility dysfunction (RVD) in echocardiography was found in 13 (23.2%) patients, who had higher ECG score compared to patients without RVD [8 (3-17) vs. 2 (0-18); p = 0.004]. The area under the ROC curve to assess the usefulness of 21-ECG score to predict RVD was 0.794 (95% CI 0.665-0.891) and for PPH 0.727 (95% CI 0.591-0.837). The sensitivity and specificity, positive and negative predictive value for the value > 3 points in 21-ECG score to predict RVD were: 92, 65, 44, 97% and for PPH: 75, 46, 19, 92%, respectively. CONCLUSIONS: 21-ECG score is a simple and cheap method which can be used to predict RVD and serious complications in patients with APE. A value L 3 points in the 21-ECG score can exclude RVD with high probability and limit the need of echocardiography to 23% of haemodynamically stable patients.

[Potential role of endothelin in patients with acute pulmonary embolism and chronic thromboembolic pulmonary hypertension]. / Potencjalne znaczenie endoteliny u chorych z ostra zatorowoscia plucna i przewleklym zatorowo-zakrzepowym nadcisnieniem plucnym.

Endothelins (ET), a family of three peptides of strong vasoconstrictive properties, participate in the regulation of vascular tone and blood flow. The synthesis and degradation of the ET predominantly take place in the pulmonary vasculature. Elevated plasma ET levels were reported in various forms of arterial pulmonary hypertension including chronic thromboembolic pulmonary hypertension (CTEPH). Moreover, clinical studies with nonselective ET receptor antagonist - bosentan reported improvement in functional class in patients with CTEPH. It has been suggested that endothelins may play an important role in acute pulmonary thromboembolism (APE). However, further studies are necessary to verify these observations. In the current paper we discuss a potential role of endothelins in CTEPH and APE.

Endothelin is not elevated in acute pulmonary embolism.

INTRODUCTION: In acute pulmonary embolism (APE) the increase of pulmonary vascular resistance depends on the thromboli load and potentially on the pulmonary bed contraction caused by neurohormonal reaction. Plasma levels of endothelin were reported to be elevated in pulmonary arterial hypertension. However, there are only a few studies assessing endothelin in patients with APE. MATERIALS & METHODS: Therefore in our study we evaluated endothelin concentration in 55 patients (29M, 26F, age 57+/-19 yrs) with confirmed APE for potential value in risk stratification. Patients were compared with 24 healthy volunteers at similar age. On admission blood samples were collected for plasma endothelin concentration. The quantitative assessment of right ventricular (RV) function was performed by echocardiography. RESULTS: Endothelin concentrations were similar in APE patients and in control group (1.41(0.22-9.68)pg/mL vs. 1.62(0.27-8.92)pg/mL; p = NS). There was no differences in endothelin levels between APE patients with and without RV dysfunction (1.46(0.38-4.54)pg/mL vs. 1.41(0.22-9.68)pg/mL; p = NS). Endothelin concentration did not differ between patients with serious adverse events and APE group with event-free clinical course (3.19(0.38-4.27)pg/mL vs. 1.38(0.22-9.68)pg/mL; p = NS). There was no significant correlation between endothelin levels and blood saturation, time from the first symptoms, heart rate, blood pressure, tricuspid valve regurgitation pressure gradient and other echocardiographic parameters. CONCLUSIONS: We concluded that plasma endothelin concentrations assessed on admission are not elevated in patients with APE and it does not play as important role in acute phase of increase of pressure in pulmonary arteries as in chronic pulmonary hypertension.