Publikacje

Bartosz Karolak, Michał Ciurzyński, Marta Skowrońska, Katarzyna Kurnicka, Magdalena Pływaczewska, Aleksandra Furdyna, Katarzyna Perzanowska-Brzeszkiewicz, Barbara Lichodziejewska, Szymon Pacho, Michał Machowski, Piotr Bienias, Małgorzata Wiśniewska, Marek Gołębiowski, Piotr Pruszczyk

Introduction: Although in the non-vitamin K oral anticoagulants (NOAC) era majority of low-risk acute pulmonary embolism (APE) patients can be treated at home, identifying those at very low risk of clinical deterioration may be challenging. We aimed to propose the risk stratification algorithm in sPESI 0 point APE patients, allowing them to select candidates for safe outpatient treatment.Materials and methods: Post hoc analysis of a prospective study of 1151 normotensive patients with at least segmental APE. In the final analysis, we included 409 sPESI 0 point patients. Cardiac troponin assessment and echocardiographic examination were performed immediately after admission. Right ventricular dysfunction was defined as the right ventricle/left ventricle ratio (RV/LV) > 1.0. The clinical endpoint (CE) included APE-related mortality and/or rescue thrombolysis and/or immediate surgical embolectomy in patients with clinical deterioration.Results: CE occurred in four patients who had higher serum troponin levels than subjects with a favorable clinical course (troponin/ULN: 7.8 (6.4-9.4) vs. 0.2 (0-1.36) p = 0.000). Receiver operating characteristic (ROC) analysis showed that the area under the curve for troponin in the prediction of CE was 0.908 (95% CI 0.831-0.984; p < 0.001). We defined the cut-off value of troponin at >1.7 ULN with 100% PPV for CE. In univariate and multivariate analysis, elevated serum troponin level was associated with an increased risk of CE, whereas RV/LV > 1.0 was not.Conclusions: Solely clinical risk assessment in APE is insufficient, and patients with sPESI 0 points require further assessment based on myocardial damage biomarkers. Patients with troponin levels not exceeding 1.7 ULN constitute the group of "very low risk" with a good prognosis.Keywords: echocardiography; pulmonary embolism; risk stratification; troponin.

Monika Lisicka, Marta Skowrońska, Bartosz Karolak, Jan Wójcik, Piotr Pruszczyk, Piotr Bienias

The association between heart rate variability (HRV) and mortality risk of acute pulmonary embolism (APE), as well as its association with right ventricular (RV) overload is not well established. We performed an observational study on consecutive patients with confirmed APE. In the first 48 h after admission, 24 h Holter monitoring with assessment of time-domain HRV, echocardiography and NT-proBNP (N-terminal pro-B-type natriuretic peptide) measurement were performed in all participants. We pre-examined 166 patients: 32 (20%) with low risk of early mortality, 65 (40%) with intermediate-low, 65 (40%) with intermediate-high, and 4 (0.02%) in the high risk category. The last group was excluded from further analysis due to sample size, and finally, 162 patients aged 56.3 ± 18.5 years were examined. We observed significant correlations between HRV parameters and echocardiographic signs of RV overload. SDNN (standard deviation of intervals of all normal beats) correlated with echocardiography-derived RVSP (right ventricular systolic pressure; r = -0.31, p = 0.001), TAPSE (tricuspid annulus plane systolic excursion; r = 0.21, p = 0.033), IVC (inferior vena cava diameter; r = -0.27, p = 0.002) and also with NT-proBNP concentration (r = -0.30, p = 0.004). HRV indices were also associated with APE risk stratification, especially in the low-risk category (r = 0.30, p = 0.004 for SDNN). Univariate and multivariate analyses confirmed that SDNN values were associated with signs of RV overload. In conclusion, we observed a significant association between time-domain HRV parameters and echocardiographic and biochemical signs of RV overload. Impaired HRV parameters were also associated with worse a clinical risk status of APE.Keywords: Holter monitoring; acute pulmonary embolism; electrocardiography; heart rate variability; right ventricle overload.

Aleksandra Justyna, Olga Dzikowska-Diduch, Szymon Pacho, Michał Ciurzyński, Marta Skowrońska, Anna Wyzgał-Chojecka, Dorota Piotrowska-Kownacka, Katarzyna Pruszczyk, Szymon Pucyło, Aleksandra Sikora, Piotr Pruszczyk

Background: Decreased hemoglobin concentration was reported to predict long term prognosis in patients various cardiovascular diseases including congestive heart failure and coronary artery disease. We hypothesized that hemoglobin levels may be useful for post discharge prognostication after the first episode of acute pulmonary embolism. Therefore, the aim of the current study was to evaluate a potential prognostic value of a decreased hemoglobin levels measured at admission due to the first episode of acute PE for post discharge all cause mortality during at least 2 years follow up. Methods: This was a prospective, single-center, follow-up, observational, cohort study of consecutive survivors of the first PE episode. Patients were managed according to ESC current guidelines. After the discharge, all PE survivors were followed for at least 24 months in our outpatient clinic. Results: During 2 years follow-up from the group of 402 consecutive PE survivors 29 (7.2%) patients died. Non-survivors were older than survivors 81 years (40−93) vs. 63 years (18−97) p < 0.001 presented higher sPESI 2 (0−4) vs. 1 (0−5), p < 0.001 driven by a higher frequency of neoplasms (37.9% vs. 16.6%, p < 0.001); and had lower hemoglobin (Hb) level at admission 11.7 g/dL (6−14.8) vs. 13.1 g/dL (3.1−19.3), p < 0.001. Multivariable analysis showed that only Hb and age significantly predicted all cause post-discharge mortality. ROC analysis for all cause mortality showed AUC for hemoglobin 0.688 (95% CI 0.782−0.594), p < 0.001; and for age 0.735 (95% CI 0.651−0.819) p < 0.001. A group of 59 subjects with hemoglobin < 10.5 g/dL showed mortality rate of 16.9% (OR for mortality 4.19 (95% CI 1.82−9.65), p-value < 0.00, while among 79 patients with Hb > 14.3 g/dL only one death was detected. Interestingly, patients in age > 64 years hemoglobin levels < 13.2 g/dL compared to patients in the same age but with >13.2 g/dL showed OR 3.6 with 95% CI 1.3−10.1 p = 0.012 for death after the discharge. Conclusions: Lower haemoglobin measured in the acute phase especially in patients in age above 64 years showed significant impact on the prognosis and clinical outcomes in PE survivors.Keywords: follow-up after pulmonary embolism; long term mortality after pulmonary embolism; predictors of survival after pulmonary embolism; pulmonary embolism.

Olga Dzikowska-Diduch, Katarzyna Kurnicka, Barbara Lichodziejewska, Iwona Dudzik-Niewiadomska, Michał Machowski, Marek Roik, Małgorzata Wiśniewska, Jan Siwiec, Izabela Magdalena Staniszewska, Piotr Pruszczyk

Background: The annual mortality of patients with untreated chronic thromboembolism pulmonary hypertension (CTEPH) is approximately 50% unless a timely diagnosis is followed by adequate treatment. In pulmonary embolism (PE) survivors with functional limitation, the diagnostic work-up starts with echocardiography. It is followed by lung scintigraphy and right heart catheterization. However, noninvasive tests providing diagnostic clues to CTEPH, or ascertaining this diagnosis as very unlikely, would be extremely useful since the majority of post PE functional limitations are caused by deconditioning. Methods: Patients after acute PE underwent a structured clinical evaluation with electrocardiogram, routine laboratory tests including NT-proBNP and echocardiography. The aim of this study was to verify whether the parameters from echocardiographic or perhaps electrocardiographic examination and NT-proBNP concentration best determine the risk of CTEPH. Results: Out of the total number of patients (n = 261, male n = 123) after PE who were included in the study, in the group of 155 patients (59.4%) with reported functional impairment, 13 patients (8.4%) had CTEPH and 7 PE survivors had chronic thromboembolic pulmonary disease (CTEPD) (4.5%). Echo parameters differed significantly between CTEPH/CTEPD cases and other symptomatic PE survivors. Patients with CTEPH/CTEPD also had higher levels of NT-proBNP (p = 0.022) but concentration of NT-proBNP above 125 pg/mL did not differentiate patients with CTEPH/CTEPD (p > 0.05). Additionally, the proportion of patients with right bundle brunch block registered in ECG was higher in the CTEPH/CTED group (23.5% vs. 5.8%, p = 0.034) but there were no differences between the other ECG characteristics of right ventricle overload. Conclusions: Screening for CTEPH/CTEPD should be performed in patients with reduced exercise tolerance compared to the pre PE period. It is not effective in asymptomatic PE survivors. Patients with CTEPH/CTED predominantly had abnormalities indicating chronic thromboembolism in the echocardiographic assessment. NT-proBNP and electrocardiographic characteristics of right ventricle overload proved to be insufficient in predicting CTEPH/CTEPD development.Keywords: chronic thromboembolic pulmonary disease; chronic thromboembolic pulmonary hypertension; diagnostic work-up of post-pulmonary syndrome; screening after pulmonary embolism.

Maciej Kostrubiec, Magdalena Pływaczewska, David Jiménez, Mareike Lankeit, Michał Ciurzyński, Stavros Konstantinides, Piotr Pruszczyk

Background: Haemodynamic alterations caused by acute pulmonary embolism (PE) may affect multi-organ function including kidneys. This multi-centre, multinational cohort study aimed to validate the prognostic significance of estimated glomerular filtration rate (eGFR) and its potential additive value to the current PE risk assessment algorithms.Methods: The post hoc analysis of pooled prospective cohort studies: 2,845 consecutive patients (1,424 M/1,421 F, 66 ± 17 years) with confirmed acute PE and followed up for 180 days. We tested prognostic value of pre-specified eGFR level ≤60 mL/min/1.73 m2 calculated on admission according to the Modification of Diet in Renal Disease study equation. The primary outcome was all-cause 30-day mortality; the secondary outcomes were PE-related mortality, 180-day all-cause mortality, bleeding and composite outcome (PE-related death, thrombolysis or embolectomy).Results: Two hundred and twenty-three patients (8%; 95% confidence interval [CI]: 7-9%) died within the first 30 days after the diagnosis. The eGFR on admission was significantly lower in non-survivors than in survivors (64 ± 34 vs. 75 ± 3 mL/min/1.73 m2, p < 0.0001). Independent predictors for a fatal outcome included: cancer, systolic blood pressure, older age, hypoxia, eGFR, heart rate and coronary artery disease. The eGFR of ≤60 mL/min/1.73 m2 independently predicted all-cause mortality (hazard ratio: 2.3; 95% CI: 1.7-3.0, p < 0.0001), PE-related outcome and clinically relevant bleedings (odds ratio: 0.90 per 10 mL/min/1.73 m2, 95% CI: 0.85-0.95, p = 0.0002). The eGFR assessment significantly improved prognostic models proposed by European guidelines with net re-classification improvement of 0.42 (p < 0.0001).Conclusion: The eGFR of ≤60 mL/min/1.73 m2 not only independently predicted higher 30- and 180-day all-cause mortality and bleeding events, but when added to the current European Society of Cardiology risk stratification algorithm improved identification of both low- and high-risk patients. Therefore, eGFR calculation should be implemented in the risk assessment of acute PE.Georg Thieme Verlag KG Stuttgart · New York.

Olga Dzikowska-Diduch, Katarzyna Kurnicka, Barbara Lichodziejewska, Olga Zdończyk, Dominika Dąbrowska, Marek Roik, Szymon Pacho, Maksymilian Bielecki, Piotr Pruszczyk

Background: We hypothesized that a Doppler index, the ratio of tricuspid regurgitation peak gradient (TRPG) to pulmonary ejection acceleration time (AcT), improves the assessment of the echocardiographic probability of pulmonary hypertension in the identification of CTEPH and chronic thromboembolic pulmonary disease (CTED) in symptomatic patients after PE. Doppler echocardiography is recommended as the initial imaging tool for the diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE). Methods: We analyzed the data from 845 consecutive PE (468 women; 61 ± 18 years) survivors who completed at least 6 months of anticoagulation therapy. Here, 555 patients (325 women; 66 ± 16 years) reporting functional impairment (FI) underwent transthoracic echocardiography. We included 506 patients (297 women; age 63.4 ± 16.6 years) in whom both AcT and TRPG were available into the current study. The presence of a minimum of intermediate echocardiographic probability of PH necessitated the diagnosis of CTEPH. Results: Echocardiography revealed a high echocardiographic probability of PH in 69 (13.6%) and intermediate echocardiographic probability in 109 (21.5%) patients. CTEPH was diagnosed in 35 (6.9%) patients and CTED in 22 (4.3%) patients. TRPG/AcT was significantly higher in the combined CTEPH + CTED group than in those with other causes of FI (0.412 (0.100–2.197) vs. 0.208 (0.026–0.115), p < 0.001), and the area under the receiver operating characteristic curve of the TRPG/AcT for CTEPH + CTED was 0.804 (95% confidence interval (CI): 0.731–0.876). Importantly, multiple logistic regression showed that TRPG/AcT is a significant predictor of CTEPH + CTED after considering echocardiographic probability (odds ratio = 1.51, 95% CI: 1.25–1.91, p < 0.001). Conditional inference trees analysis revealed that TRPG/AcT > 0.595 identified patients with CTEPH or CTED with a positive predictive value of 78.6% and negative predictive value of 92.7%. Conclusions: A Doppler index TRPG/AcT improves the assessment of symptomatic PE survivors. TRPG/AcT > 0.6 indicates a high probability of CTEPH or CTED, whereas TRPG/AcT < 0.6 allows for the safe exclusion of CTEPH + CTED in patients with a low echocardiographic probability of PH.

Magdalena Pływaczewska, David Jiménez, Mareike Lankeit, Piotr Pruszczyk, Maciej Kostrubiec

Introduction: Risk stratification is mandatory for optimal management of patients with acute pulmonary embolism (APE). Previous studies indicated that renal dysfunction predicts outcome and can improve risk assessment in APE.Aim: The aim of the study was a comparison of estimated glomerular filtration rate (eGFR) formulas, MDRD, and Cockcroft-Gault (CG), in the prognostic assessment of patients with APE.Materials and methods: Data from 2274 (1147 M/1127 F, median 71 years) hospitalised patients with APE prospectively included in a multicenter, observational, cohort study were analysed. A serum creatinine measurement as a routine laboratory parameter at the cooperating centers and eGFR calculation were performed on admission. Patients were followed for 180 days. The primary outcome was death from any cause within 30 days.Results: The eGFR levels assessed by both, MDRD (eGFRMDRD) and CG formula (eGFRCG), were highest in patients with low-risk APE and lowest in high-risk APE. The eGFR (using both methods) was significantly lower in nonsurvivors compared to survivors. Using a threshold of <60 ml/min/1.73 m2, eGFRMDRD revealed the primary outcome with sensitivity 67%, specificity 52%, PPV 8%, and NPV 97%, while eGFRCG had a sensitivity 62%, specificity 62%, PPV 8.6%, and NPV 96%. The area under the ROC curve for eGFRCG tended to be higher than that for eGFRMDRD: 0.658 (95% CI: 0.608-0.709) vs. 0.631 (95% CI: 0.578-0.683), p = 0.12. A subanalysis of ROC curves in a population above 65 yrs showed a higher AUC for eGFRCG than based on MDRD. Kaplan-Meier analysis showed a worse long-term outcome in patients with impaired renal function.Conclusion: eGFRMDRD and eGFRCG assessed on admission significant short- and long-term mortality predictors in patients with APE. The eGFRCG seems to be a slightly better 30-day mortality predictor than eGFRMDRD in the elderly.Copyright © 2021 Magdalena Pływaczewska et al.

Katarzyna Kurnicka, Barbara Lichodziejewska, Michał Ciurzyński, Maciej Kostrubiec, Sylwia Goliszek, Olga Zdończyk, Olga Dzikowska-Diduch, Piotr Palczewski, Marta Skowrońska, Marcin Koć, Katarzyna Grudzka, Piotr Pruszczyk

Background: Tricuspid annular plane systolic excursion (TAPSE) is an established index of right ventricular (RV) systolic function and a significant predictor in normotensive patients with pulmonary embolism (PE). Recently, Doppler tissue imaging-derived tricuspid annular systolic velocity (TV S'), a modern parameter of RV function was reported to be useful in the diagnosis and prognosis of a broad spectrum of heart diseases. Therefore, herein, is an analysis of the prognostic value of both parameters in normotensive PE patients.Methods: One hundred and thirty nine consecutive PE patients (76 female, age 56.4 ± 19.5 years) were included in this study. All patients were initially anticoagulated. Transthoracic echocardiography was performed on admission. The study endpoint (SE) was defined as PE-related 30-day mortality and/or need for rescue thrombolysis.Results: Seven (5%) patients who met the criteria for SE presented more severe RV dysfunction at echocardiography. Univariable Cox regression analysis showed that RV/LV ratio predicted SE with hazard risk (HR) 10.6 (1.4-80.0; p = 0.02); TAPSE and TV S' showed HR 0.77 (0.67-0.89), p < 0.001, and 0.71 (0.52-0.97), p = 0.03, respectively. Area under the curve for TAPSE in the prediction of SE was 0.881; 95% CI 0.812-0.932, p = 0.0001, for TV S' was 0.751; 95% CI 0.670-0.820, p = 0.001. Multivariable analysis showed that the optimal prediction model included TAPSE and systolic blood pressure (SBP showed HR 0.89 95% CI 0.83-0.95, p < 0.001 and TAPSE HR 0.67, 95% CI 0.52-0.87, p<0.03). Kaplan-Meier analysis showed that initially PE patients with TAPSE ≥ 18 mm had a much more favorable prognosis that patients with TAPSE < 18 mm (p < 0.01), while analysis of S' was only of borderline statistical significance.Conclusions: It seems that TV S' is inferior to TAPSE for 30 day prediction of adverse outcome in acute pulmonary embolism.Keywords: Doppler tissue imaging; prognosis; pulmonary embolism; right ventricular function; transthoracic echocardiography; tricuspid valve.

Marta Skowrońska, Martyna Skrzyńska, Michał Machowski, Zbigniew Bartoszewicz, Marzanna Paczyńska, Aisha Ou-Pokrzewińska, Katarzyna Kurnicka, Michał Ciurzyński, Marek Roik, Małgorzata Wiśniewska, Piotr Palczewski, Piotr Pruszczyk

Introduction: Growth differentiation factor 15 (GDF‑15), a cytokine induced in the myocardium by pressure overload and ischemia, has a well‑established prognostic role for diseases of the left ventricle. Plasma GDF‑15 concentrations were shown to predict bleeding events in patients with atrial fibrillation on anticoagulation.Objectives: To investigate the prognostic value of GDF‑15 in acute pulmonary embolism (PE).Patients and methods: This was a prospective observational study of 77 patients hospitalized for PE. The median length of hospital stay and follow-up was 9 days. Plasma GDF‑15 levels were measured using an automated sandwich electrochemiluminescence immunoassay. The outcome measures were: 1) in‑hospital serious adverse events (SAE; death, cardiopulmonary resuscitation, need for urgent reperfusion therapy, catecholamine administration), and 2) major bleeding or nonmajor clinically relevant bleeding.Results: There were 12 SAE and 5 bleeding events. The median (interquartile range) GDF‑15 concentration at admission was 2354 ng/l (1151-4750 ng/l). GDF‑15 concentrations increased according to risk subgroup. Patients with serious adverse events or bleeding events had higher baseline concentrations of GDF‑15 (median [interquartile range], 3460 ng/l [2 531-12 363 ng/l] vs 2034 ng/l [1121-4449 ng/l]; P = 0.01). The area under the curve for GDF‑15, high‑sensitivity cardiac troponin T, and N‑terminal pro-brain natriuretic peptide concentrations for predicting SAE was similar, the area under the curve of GDF‑15 levels for predicting bleeding was 0.783 (95% CI, 0.62-0.946; P = 0.001) and 0.71 (95% CI, 0.567-0.853; P = 0.004) for predicting any adverse event. In the multivariable analysis, GDF‑15 greater than 1680 ng/l emerged as an independent predictor of adverse outcomes (odds ratio, 8.9; P = 0.047).Conclusions: Plasma GDF‑15 concentrations may be a promising biomarker for predicting hemodynamic destabilization and bleeding complications in PE.

Monika Sznajder, Olga Dzikowska-Diduch, Katarzyna Kurnicka, Marek Roik, Dominik Wretowski, Piotr Pruszczyk, Maciej Kostrubiec

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of venous thromboembolism (VTE) resulting from non-dissolving thromboemboli in the pulmonary arteries. Previous observations indicate a higher prevalence of atherosclerosis and cardiovascular risk factors in patients with VTE and CTEPH. The purpose of the present study was to evaluate the arterial stiffening assessed by pulse wave velocity (PWV), a marker of arterial stiffness, in CTEPH patients in comparison with a matched control group (CG).Methods: The study group consisted of 26 CTEPH patients (9 male and 17 female, age 69 ± 10 years) and 22 CG (10 male, 12 female, age 67 ± 8 years). In all subjects a physical examination, carotid-femoral PWV and transthoracic echocardiography were performed. Right heart catheterization was done in all CTEPH.Results: Chronic tromboembolic pulmonary hypertension patients had significantly higher PWV than CG (10.3 ± 2.5 m/s vs. 9 ± 1.3 m/s, p < 0.05), even though systolic blood pressure was higher in CG (120 ± 11 vs. 132 ± 14 mmHg, p = 0.002). PWV correlated only with age and pulmonary vascular resistance (PVR) in CTEPH (r = 0.45, p = 0.03 and r = 0.43, p = 0.03, respectively). Arterial stiffening defined as PWV > 10 m/s was found in 11 (42%) CTEPH patients and in 5 (23%) cases from CG (p = 0.13). CTEPH patients with PWV > 10 m/s were older (74 ± 8 vs. 66 ± 10 years, p < 0.05), had decreased oxygen saturation (SaO2 89 [73-96]% vs. 96 [85-98]%, p < 0.01) and tended to have higher PVR (8.1 [3.1-14.0] vs. 5.2 [3.1-12.7] HRU, p = 0.10).Conclusions: Arterial stiffness, assessed with PWV, is increased in CTEPH. The elevated PWV is associated with older age, lower SaO2 and higher PVR in CTEPH.Keywords: arterial stiffness; atherosclerosis; chronic thromboembolic pulmonary hypertension; pulse wave velocity.