Publikacje

Maciej Kostrubiec, Piotr Pruszczyk, Anna Kaczyńska, NIls Kucher

Aims: Low levels of brain natriuretic peptides on admission identify low-risk patients with acute pulmonary embolism (APE) through their high NPV for mortality. However, increased natriuretic peptide values on admission are less helpful for identifying high-risk patients due to their low PPV. The aim of the study was to test whether the PPV for mortality can be improved by performing serial NT-proBNP measurements on admission, at 12 h, and at 24 h.Methods and results: We prospectively included 113 consecutive patients with APE (mean age 63+/-18 years), of whom 10 had clinically massive APE. Thirty-day mortality was 15% (95% CI: 8%-22%). In survivors, median NT-proBNP levels decreased within 24 h from 1895 ng/L (range: 16-33,340) to 1007 ng/L (range: 9-33,243) (p<0.001). In non-survivors, median NT-proBNP levels at baseline (11,491 ng/L, range: 618-60,958) remained elevated at 24 h (8139 ng/L, range: 35-70,018; p=NS). The 30-day mortality rate in the group of 18 patients with NT-proBNP >7500 ng/L and less than 50% decrease of NT-proBNP within 24 h was 61% (95% CI: 39%-84%). PPV and NPV of NT-proBNP >7500 ng/L on admission and less than 50% decrease of NT-proBNP within 24 h were 61% and 94%, respectively.Conclusion: Persistent elevation of plasma NT-proBNP levels within 24 h after APE diagnosis indicates ongoing right ventricular dysfunction with a poor prognosis. These critically ill patients may be candidates for rapid aggressive intervention, including thrombolysis, catheter thrombectomy, or surgical embolectomy.

Andrzej Łabyk, Anna Kalbarczyk, Agata Piaszczyk, Maciej Kostrubiec, Anna Kaczyńska, Anna Bochowicz, Piotr Pruszczyk

Introduction: The mortality of untreated pulmonary embolism (PE) is estimated at approximately 30% of patients, whereas treatment decreases it to 2-8%. A specific combination of symptoms present in PE may suggest other cardiac or lung disorder.Objectives: To evaluate frequencies of clinical symptoms and changes in diagnostic investigations misleading to the recognition of acute coronary syndrome (ACS) or lung diseases (Ld) in PE patients.Patients and methods: Retrospective analysis of 154 records of individuals with recognized PE allowed to divide patients into groups suggestive of ACS (min. 2 of: chest pain, ischemic changes on electrocardiogram (ECG) and elevated cardiac troponin T level [cTnT >0.01 ng/ml]) or suggestive of the Ld (min. 2 of: dyspnea, cough, fever, lung consolidations on chest radiograph).Results: Fifty-five (36%) patients were classified to the ACS group and 54 (35%) to Ld group, while 69 (45%) patients were not included to either group. Twenty-four (16%) patients fulfilled criteria of both groups. There were no significant differences in the frequency of coronary heart disease, heart failure, atrial fibrillation and chronic obstructive pulmonary disease between groups. Elevated troponin level was observed in 68% of patients with chest pain and changes on ECG, and in 26% of patients without coexistence of these symptoms (p < 0.05).Conclusions: In most patients with final diagnosis of PE, symptoms and initial investigation results can mislead to the diagnosis of ACS or lung disease. The chest pain and ischemic changes on ECG are frequently associated with the myocardial injury resulting in increased troponin levels in PE patients.

Anna Kaczyńska, Maciej Kostrubiec, Ryszard Pacho, Jolanta Kunikowska, Piotr Pruszczyk

Background: Despite long-term anticoagulation in some patients after acute pulmonary embolism (APE) pulmonary thrombi are not completely resolved. We hypothesized that elevated D-dimer concentration reflecting increased endogenous fibrinolysis may indicate incomplete pulmonary thrombi resolution after the first episode of PE.Methods: 55 patients aged 54.7+/-18.6 years were anticoagulated for 6 months with acenocumarol (74.5% patients) or low molecular weight heparin (25.5% patients) when control spiral computed tomography (sCT), lung perfusion scintigraphy and D-dimer assessment were performed.Results: Incomplete recanalization of pulmonary circulation was found in 39 (70.9%) patients - thrombi at sCT and/or > or =1 wedge-shaped perfusion defect at scintigraphy. Age, sex, rate of unprovoked APE, malignancies, thrombolysis in the acute phase and type of long-term anticoagulation were similar in patients without and with complete recanalization. D-dimer at follow-up but not on admission was higher in patients with then without incomplete recanalization (median 340 (80-2280) vs 160 (60-390) ng/mL, p=0.02). All 11 (20%) patients with D-dimer level >500 ng/mL at follow-up did not resolve thromboemboli completely. ROC analysis showed that D-dimer at follow-up identified patients with incomplete recanalization (AUC 0.709, 95% CI (0.560-0.831), p=0.007). Multivariable analysis confirmed that D-dimer >350 ng/mL at follow-up and right ventricle dysfunction at the diagnosis were independent predictors of incomplete recanalization (OR 18.58 (95% CI 1.97-175.19) and 7.03 (95% CI 1.43-34.6), respectively, p=0.0006).Conclusion: Elevated D-dimer after 6 months anticoagulation and right ventricular dysfunction at the diagnosis predict incomplete recanalization of pulmonary circulation after first episode of APE.

Anna Kaczyńska, Marcin Szulc, Grzegorz Styczyński, Maciej Kostrubiec, Ryszard Pacho, Piotr Pruszczyk

Right ventricular (RV) overload and hypoxia in acute pulmonary embolism (APE) may lead to RV myocardium injury reflected by elevated cardiac troponin levels. We studied 26 patients aged 57.2+/-17.8 years with first episode of APE. On admission troponin T (TnT) was measured. Transthoracic echocardiography was performed after 6 months of anticoagulation. Myocardial injury (TnT > or =0.03 ng/ml) was observed in 8 (30.8%) patients at the diagnosis. At follow up RV diastolic area tended to be larger in group with myocardial injury (25.0 (20.8-38.6) vs 18.4 (17.7-23.3) cm(2), p=0.06). Tricuspid annulus systolic velocity at tissue Doppler was lower in group with myocardial injury (0.12 (0.11-0.13) vs 0.15 (0.13-0.21) m/s, p=0.04), while no such a relationship was found for mitral annulus systolic velocity. TnT concentration correlated with RV diastolic area (r=0.61) and tricuspid annulus systolic velocity (r=-0.58) although not significantly (p=0.08 and p=0.09. respectively). Our data suggest that RV injury in acute phase of PE may lead to its remodeling.

Maciej Kostrubiec, Justyna Pedowska-Włoszek, Michał Ciurzyński, Piotr Bienias, Szymon Pacho, Marzena Piaskowska, Piotr Pruszczyk

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.

Krzysztof Jankowski, Maciej Kostrubiec, Patrycja Ozdowska, Blanka Milanowska-Puncewicz, Szymon Pacho, Justyna Pedowska-Włoszek, Anna Kaczyńska, Andrzej Łabyk, Anna Hrynkiewicz, Piotr Pruszczyk

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.

M. Kostrubiec, A. Łabyk, J. Pedowska-Włoszek, S. Pacho, A. Wojciechowski, K. Jankowski, M. Ciurzyński, P. Pruszczyk

Objective: Current risk stratification in acute pulmonary embolism (APE) includes assessment of clinical status, right ventricular overload and plasma troponin concentrations. As impaired renal function is one of the important predictors of mortality in cardiovascular diseases, we hypothesized that it is an independent early mortality marker in APE.Material and methods: In prospective cohort study, we observed 220 consecutive patients (86M/134F, 64 +/- 18 years) with APE proven by spiral computed tomography (CT). On admission, echocardiography was performed and blood samples were collected for troponin and creatinine assays.Results: The calculated glomerular filtration rate (GFR) differed significantly between 81 pts with low-, 131 pts with moderate- and 8 pts with high-risk APE [71 (19-181) vs. 55 (9-153) vs. 41 (14-68) mL min(-1); respectively P < 0.0001]. Twenty-three patients died during the 30-day observation. Importantly, GFR was lower in non-survivors than in survivors [35 (9-92) vs. 63 (14-181) mL min(-1), P < 0.0001]. The area under the curve (AUC) of the GFR receiver-operating characteristic (ROC) curve for predicting mortality was 0.760 (95% CI: 0.698-0.815). In multivariable analysis, independent mortality predictors were GFR, troponin, heart rate and history of chronic heart failure. In normotensive patients, the GFR and cardiac troponins (cTn) ROC curves for prediction of mortality showed no difference (AUC 0.789 and 0.781, respectively). However, Kaplan-Meier analysis showed an additive prognostic value of renal dysfunction. Thus, troponin-positive patients with a GFR < or = 35 mL mn(-1) showed 48% 30-day mortality, whereas troponin-positive patients with a GFR > 35 mL mn(-1) had 11% mortality, and troponin-negative patients with a GFR > 35 mL mn(-1) had good prognosis, P < 0.0001.Conclusion: Impaired kidney function, present in 47% of APE patients, is related to all-cause mortality. In initially normotensive patients, a GFR < 35 mL min(-1) predicts 30-day mortality. Moreover, GFR assessment can improve troponin-based risk stratification of APE.

Maciej Kostrubiec, Andrzej Łabyk, Justyna Pedowska-Włoszek, Anna Hrynkiewicz-Szymańska, Szymon Pacho, Krzysztof Jankowski, Barbara Lichodziejewska, Piotr Pruszczyk

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.

Andrzej Łabyk, Michał Ciurzyński, Krzysztof Jankowski, Maciej Kostrubiec, Barbara Lichodziejewska, Piotr Bienias, Justyna Pedowska-Włoszek, Szymon Pacho, Piotr Palczewski, Piotr Pruszczyk

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.

Maciej Kostrubiec, Andrzej Łabyk, Justyna Pedowska-Włoszek, Olga Dzikowska-Diduch, Artur Wojciechowski, Marzena Garlińska, Michał CIurzyński, Piotr Pruszczyk

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.