Maciej Kostrubiec

N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism.

Plasma brain natriuretic peptide (BNP), released from myocytes of ventricles upon stretch, has been reported to differentiate pulmonary from cardiac dyspnoea. Limited data have shown elevated plasma BNP levels in acute pulmonary embolism (APE), frequently accompanied by dyspnoea and right ventricular (RV) dysfunction. The aim of this study was to assess plasma N‐terminal proBNP (NT‐proBNP) in APE, and to establish whether it reflects the severity of RV overload and if it can be used to predict adverse clinical outcome. On admission, NT‐proBNP and echocardiography for RV overload were performed in 79 APE patients (29 males), aged 63±16 yrs. Plasma NT‐proBNP was elevated in 66 patients (83.5%) and was higher in patients with (median 4,650 pg·mL−1 (range 61–60,958)) than without RV strain (363 pg·mL−1 (16–16,329)). RV‐to-left ventricular ratio and inferior vena cava dimension correlated with NT‐proBNP. All 15 in-hospital deaths and 24 serious adverse events occurred in the group with elevated NT‐proBNP, while all 13 (16.5%) patients with normal values had an uncomplicated clinical course. Plasma NT‐proBNP predicted in-hospital mortality. Plasma N‐terminal pro-brain natriuretic peptide is elevated in the majority of cases of pulmonary embolism resulting in right ventricular overload. Plasma levels reflect the degree of right ventricular overload and may help to predict short-term outcome. Acute pulmonary embolism should be considered in the differential diagnosis of patients with dyspnoea and abnormal levels of brain natriuretic peptide.

Predictive Value of the High-Sensitivity Troponin T Assay and the Simplified Pulmonary Embolism Severity Index in Hemodynamically Stable Patients With Acute Pulmonary Embolism A Prospective Validation Study

Background— The new, high-sensitivity troponin T (hsTnT) assay may improve risk stratification of normotensive patients with acute pulmonary embolism (PE). We externally validated the prognostic value of hsTnT, and of the simplified Pulmonary Embolism Severity Index (sPESI), in a large multicenter cohort. Methods and Results— We prospectively examined 526 normotensive patients with acute PE; of those, 31 (5.9%) had an adverse 30-day outcome. The predefined hsTnT cutoff value of 14 pg/mL was associated with a high prognostic sensitivity and negative predictive value, comparable to those of the sPESI. Both hsTnT ≥14 pg/mL (OR, 4.97 [95% CI, 1.71–14.43]; P=0.003) and sPESI ≥1 point(s) (OR, 9.51 [2.24–40.29]; P=0.002) emerged, besides renal insufficiency (OR, 2.97 [1.42–6.22]; P=0.004), as predictors of early death or complications; in a multivariable model, they remained independent predictors of outcome (P=0.044 and 0.012, respectively). A total of 127 patients (24.1%) were identified as low risk by a sPESI of 0 and hsTnT <14 pg/mL; none of them had an adverse 30-day outcome. During 6-month follow-up, 52 patients (9.9%) died. Kaplan-Meier analysis illustrated that patients with hsTnT ≥14 pg/mL (P=0.001) and those with sPESI ≥1 (P<0.001) had a decreased probability of 6-month survival. Patients with sPESI of 0 and hsTnT <14 pg/mL at baseline had a 42% reduction in the risk of dying (hazard ratio, 0.58 [0.01–0.42]; P=0.005). Conclusions— The hsTnT assay and the sPESI improve risk stratification of acute PE. Combination of both modalities may yield additive prognostic information and particularly identify possible candidates for out-of-hospital treatment.

Validation of N-terminal pro-brain natriuretic peptide cut-off values for risk stratification of pulmonary embolism

The optimal N-terminal pro-brain natriuretic peptide (NT-proBNP) cut-off value for risk stratification of pulmonary embolism remains controversial. In this study we validated and compared different proposed NT-proBNP cut-off values in 688 normotensive patients with pulmonary embolism. During the first 30 days, 28 (4.1%) patients reached the primary outcome (pulmonary embolism-related death or complications) and 29 (4.2%) patients died. Receiver operating characteristic analysis yielded an area under the curve of 0.70 (0.60–0.80) for NT-proBNP. A cut-off value of 600 pg·mL−1 was associated with the best prognostic performance (sensitivity 86% and specificity 50%) and the highest odds ratio (6.04 (95% CI 2.07–17.59), p=0.001) compared to the cut-off values of 1000, 500 or 300 pg·mL−1. Using multivariable logistic regression analysis, NT-proBNP ≥600 pg·mL−1 had a prognostic impact on top of that of the simplified Pulmonary Embolism Severity Index and right ventricular dysfunction on echocardiography (OR 4.27 (95% CI 1.22–15.01); p=0.024, c-index 0.741). The use of a stepwise approach based on the simplified Pulmonary Embolism Severity Index, NT-proBNP ≥600 pg·mL−1 and echocardiography helped optimise risk assessment. Our findings confirm the prognostic value of NT-proBNP and suggest that a cut-off value of 600 pg·mL−1 is most appropriate for risk stratification of normotensive patients with pulmonary embolism. NT-proBNP should be used in combination with a clinical score and an imaging procedure for detecting right ventricular dysfunction. Stepwise approach based on sPESI, NT-proBNP and echocardiography for pulmonary embolism risk stratification http://ow.ly/tsMud

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.

Prognostic Value of Echocardiography in Normotensive Patients With Acute Pulmonary Embolism

OBJECTIVES The goal of the study was to evaluate the prognostic value of echocardiographic indices of right ventricular dysfunction (RVD) for prediction of pulmonary embolism-related 30-day mortality or need for rescue thrombolysis in initially normotensive patients with acute pulmonary embolism (APE). BACKGROUND There is no generally accepted echocardiographic definition of RVD used for prognosis in APE. METHODS We studied the prognostic value of a set of echocardiographic parameters in 411 consecutive patients (234 women, age 64 ± 18 years) with APE hemodynamically stable at admission. RESULTS Thirty-day APE-related mortality was 3% (14 patients), all-cause mortality was 5% (21 patients). Nine patients received thrombolysis as a result of hemodynamic deterioration, and 7 of them survived. The clinical endpoint (CE), which included APE-related death or thrombolysis, occurred in 21 patients. At univariable Cox analysis, the hazard ratio (HR) for CE of the right ventricular (RV)/left ventricular (LV) ratio was 7.3 (95% confidence interval [CI]: 2.0 to 27.3; p = 0.003). However, multivariable analysis showed that tricuspid annulus plane systolic excursion (TAPSE) was the only independent predictor (HR: 0.64, 95% CI: 0.54 to 0.7; p < 0.0001). Moreover, the area under the curve (AUC) in receiver-operating characteristic analysis for TAPSE (0.91, 95% CI: 0.856 to 0.935; p = 0.0001) in CE prediction was higher (p < 0.001) than AUC of RV/LV ratio (0.638, 95% CI: 0.589 to 0.686; p = 0.001). TAPSE ≤15 mm had a HR of 27.9 (95% CI: 6.2 to 124.6; p < 0.0001) and a positive predictive value (PPV) of 20.9% for CE with a 99% negative predictive value (NPV), whereas TAPSE ≤20 mm had a PPV of 9.2 with a 100% NPV. RV/LV ratios of >0.9 and >1.0 had a PPV of 13.2% and 14.4% and a NPV of 97% and 94.3%, respectively. CONCLUSIONS TAPSE is preferable to the RV/LV ratio for risk stratification in initially normotensive patients with APE. TAPSE ≤15 mm identifies patients with an increased risk of 30-day APE-related mortality, whereas TAPSE >20 mm can be used for identification of a very low-risk group.

Assessment of renal dysfunction improves troponin‐based short‐term prognosis in patients with acute symptomatic pulmonary embolism

Summary.  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 ≤ 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.

Refined balloon pulmonary angioplasty driven by combined assessment of intra-arterial anatomy and physiology – Multimodal approach to treated lesions in patients with non-operable distal chronic thromboembolic pulmonary hypertension – Technique, safety and efficacy of 50 consecutive angioplasties

BACKGROUND/OBJECTIVES Balloon pulmonary angioplasty (BPA) is an emerging therapeutic method in CTEPH. We aimed to prove the safety and efficacy of refined BPA driven by combined assessment of intra-arterial anatomy (IVUS/OCT) and physiology (pulmonary pressure ratio, PPR) in non-operable distal CTEPH. METHODS 11 pts (mean age 76, 59–84, 7 males) were enrolled in the BPA program according to the following inclusion criteria: 1. Non-operable CTEPH; 2. RHC with mPAP > 30 mm Hg; 3. At least one segmental perfusion defect at lung scintigraphy; 4. WHO class > II. Overall, 9 pts underwent 27 BPA sessions (mean 3 sessions per patient, range 1–5), 50 pulmonary arteries were dilated (mean 6 vessels per patient, range 3–9; 2.03 dilated arteries per session). All the angioplasties were performed according to an algorithm, which incorporated anatomical and functional assessment of targeted lesions. RESULTS We performed BPA of 32 web lesions, 5 ring-like stenosis and 13 complete obstructions. BPA resulted in clinical and hemodynamic improvement. WHO class improved from pre-BPA to post-BPA (p = 0.018), and 6 MWD increased from 304 m to 384 m (p = 0.03), NT-proBNP dropped from 1248 pg/ml to 730 pg/ml (p < 0.001). Mean PAP and PVR decreased (p = 0.01), while CO and CI increased (p = 0.01). All dilated arteries were patent at angiographic reassessment. No significant complications occurred and all treated patients are still alive. Insignificant transient reperfusion pulmonary oedema occurred in only 2 patients, who responded well to supplemental oxygen. CONCLUSIONS Refined BPA with assessment of intrapulmonary physiology using a pressure wire and precise evaluation of anatomy with IVUS and OCT provides hemodynamic and functional improvement, with minimal complications in distal non-operable CTEPH. This observation requires further validation in a large prospective study.

Derivation of a clinical prediction score for chronic thromboembolic pulmonary hypertension after acute pulmonary embolism

Essentials Predicting chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism is hard. We studied 772 patients with pulmonary embolism who were followed for CTEPH (incidence 2.8%). Logistic regression analysis revealed 7 easily collectable clinical variables that combined predict CTEPH. Our score identifies patients at low (0.38%) or higher (10%) risk of CTEPH.

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.

Homocysteine, Adrenergic Activity and Left Ventricular Mass in Patients with Essential Hypertension

Objective: Assessment of relationship between homocysteine (Hcy) and noradrenaline (NA), adrenaline (A) concentration and left ventricular mass index (LVMI) in patients with essential hypertension (EH). Design and methods: Samples obtained from 37 patients (14 female, 23 male) with mild EH (according to WHO criteria) (mean age 43.6 - 13.2 years) and 37 healthy volunteers (18 female, 19 male; mean age 38.2 - 10.6 years) were evaluated for Hcy (ELISA), NA and A (HPLC). Each patient underwent echocardiographic investigation with LVMI measurement (Penn convention). The examinations were performed in the outpatient clinic. Results: Hcy was significantly higher in patients with EH (8.7 - 2.4 vs 6.6 - 1.3 µmol/l; p < 0.01). NA and A levels were significantly elevated in the EH group (A: 43.9 - 26.4 vs 36.9 - 29.4 pg/ml; NA: 428.5 - 148.8 pg/ml vs 314.6 - 103.4 pg/ml; both p < 0.05). LVMI was also significantly higher in EH group (96.6 - 19.5 vs 83.4 - 16.0 g/m 2; p < 0.01). There was no significant correlation between Hcy and other analysed parameters in the studied groups. Conclusion: High levels of Hcy appear together with increased left ventricular mass and augmented adrenergic activity in patients with EH. Coexistence of high Hcy concentration, left ventricular hypertrophy and increased adrenergic activity increases the risk of atherosclerosis and cardiovascular disease in patients with EH. Key words: