Olga Dzikowska-Diduch

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.

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.

E-selectin and sICAM-1, biomarkers of endothelial function, predict recurrence of venous thromboembolism

BACKGROUND Risk factors for atherosclerosis and venous thromboembolism (VTE) overlap and are mostly associated with endothelial dysfunction (ED). We hypothesized that ED is present in patients after the first episode of acute pulmonary embolism (APE) and predicts the risk of VTE recurrence. DESIGN AND METHODS Patients, at least 6months after the first episode of symptomatic, confirmed APE were included in this case-control study. The exclusion criteria were risk factors for cardiovascular diseases and other conditions associated with endothelial dysfunction. Eighty two patients (aged 38±11years; 44 M; 38 F) were enrolled in the study, 39 after provoked APE, 43 after unprovoked APE, and 30 controls (C) (aged 38±12years; 15 M, 15 F). In order to evaluate the endothelial function in patients with a history of APE flow-mediated dilation (FMD) of the brachial artery and biomarkers of endothelial dysfunction (sVCAM-1, sICAM-1, ADMA, E-selectin) were measured. Subsequently all patients were followed up in an outpatient clinic for VTE recurrence. RESULTS FMD was more often impaired in APE patients than in controls (5.3% (0.8-20.3) vs. 13.8% (4.1-24.3); p<0.0001). Biomarker levels differed between APE and C groups: sVCAM-1 (631ng/ml (105-2382) vs. 495ng/ml (348-934); p=0.04) and sICAM-1 (679ng/ml (279-1006) vs. 600ng/ml (394-766); p=0.002). There were 19 recurrences of VTE during the at least 12-month follow-up (15 with history of unprovoked-APE and 4 after provoked-APE). E-selectin ≥39ng/ml and sICAM-1≤655ng/ml indicated the group without recurrence of VTE. In a group of 43 unprovoked APE patients both E-selectin<39ng/ml and sICAM-1>655ng/ml were found in 17 subjects. Eleven of them (65%) were diagnosed with recurrent VTE. CONCLUSIONS Endothelial function is significantly impaired in patients after an episode of APE as indicated by FMD assessment and biomarker levels. Low concentrations of E-selectin and high levels of sICAM-1 are associated with a high risk of recurrent thromboembolism.

Refined balloon pulmonary angioplasty—A therapeutic option in very elderly patients with chronic thromboembolic pulmonary hypertension

INTRODUCTION/OBJECTIVES Balloon pulmonary angioplasty (BPA) is a developing treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, to our knowledge there are no published data on BPA in CTEPH subjects aged 75 or over. The aim of the study was to analyze clinical and hemodynamic outcomes of sequential BPA in very elderly patients disqualified from pulmonary endarterectomy (PEA). PATIENTS AND METHODS We enrolled 10 patients (4 male, 6 female, median age 81 [75-88]) with confirmed CTEPH, mPAP > 30 mmHg, and WHO class > II, disqualified from PEA. Overall, 10 patients underwent 39 BPA sessions (mean 3.9 sessions per patient, range 1-9), and 70 pulmonary arteries were dilated, (mean 6.5 vessels per patient, range 1-14). RESULTS Pulmonary angioplasty resulted in significant clinical and hemodynamic improvement in every patient: 6 MWT distance increased from a median of 221 m (80-320) to 345 (230-455) and plasma NT-proBNP levels decreased (P < 0.01). Sequential BPA resulted in normalization of mPAP (<25 mmHg) in 6 of 10 patients and mPAP decreased to 25-30 mmHg in three others. In the whole group mPAP decreased from 41 (31-53) mmHg to 23 (17-33) mmHg (P < 0.01). Overall, mean PAP and PVR decreased significantly in all cases, while CO and CI increased (P < 0.01). No severe complications occurred during BPA and over a median follow-up of 553 days (range 81-784), and all patients are still alive and in good general health. CONCLUSION This study demonstrated the safety and efficacy of refined BPA in CTEPH patients aged 75 or over, disqualified from PEA. Refined BPA may emerge as an alternative therapeutic strategy in very elderly CTEPH patients who are suitable for surgery, but this requires further validation in a large prospective study.

Acute pulmonary embolism treatment with rivaroxaban results in a shorter duration of hospitalisation compared to standard therapy: an academic centre experience.

BACKGROUND Depending on the severity of clinical condition, acute pulmonary embolism (APE) is treated with unfraction-ated heparin (UFH), low-molecular weight heparin (LMWH), oral anticoagulants or, in the most severe form, with fibrinolytic agents. Following APE, patients require prolonged anticoagulant therapy for 3-6 months or in some cases indefinitely. Treatment options in this period include vitamin K antagonists (VKA) and non-VKA oral anticoagulants (NOAC) including rivaroxaban. The most recent European Society of Cardiology guidelines on the diagnosis and management of APE recommend use of NOAC in patients at a low-to-moderate risk of early mortality (a class I B recommendation). Rivaroxaban may be used in haemodynamically stable patients since the first day of therapy and was approved for this indication in Poland in December 2012. AIM To evaluate the rate of rivaroxaban use, characterise patients with APE treated with rivaroxaban, and evaluate potential reduction of the duration of hospitalisation in patients treated with rivaroxaban compared to those receiving VKA. METHODS We evaluated hospital and postdischarge treatment in 215 consecutive APE patients (105 men, 110 women) at the mean age of 65.0 (range: 19.5-91.9) years. The study included patients hospitalised from January 2013 to November 2014, i.e. in the period immediately following approval of rivaroxaban for the treatment of APE in Poland. In the acute phase, patients were treated with LMWH, UFH, or rivaroxaban, and the treatment was continued with VKA, LMWH, or rivaroxaban. The timing of initiation of oral therapy depended on the haemodynamic stability of the patient. RESULTS Our study group of 215 APE patients included 157 (73%) moderate-risk patients, 51 (24%) low-risk, and 7 (3.3%) high-risk patients. Treatment was initiated with UFH or LMWH in 208 (96.7%) patients, and with rivaroxaban in 7 (3.3%) patients. In 33 (16.5%) patients, rivaroxaban was started after up to 3 days of heparin therapy. Chronic therapy prescribed at discharge in-cluded VKA in 64 (30.5%) patients, rivaroxaban in 82 (39%) patients, and LMWH in 64 (30.5%) patients. Five patients died during hospital, for the total mortality of 2.3%. Acute high-risk PE was diagnosed on admission in 2 of these patients, and moderate-risk PE in 3 patients. Treatment in this group included enoxaparin in 4 patients and UFH in 1 patient. Patients who were discharged on rivaroxaban stayed in hospital for a significantly shorter time compared to patients discharged on VKA (6 [2-22] vs. 8 [2-17] days, p = 0.0005). Duration of hospital stay was significantly shorter in APE patients with sPESI of 0 who were treated with rivaroxaban compared to those with sPESI of 0 treated with VKA (5 [2-11] vs. 6 [2-12] days, p = 0.002). A significant difference in the duration of hospital stay was also noted in patients with sPESI of ≥ 1 treated with rivaroxaban compared to those treated with VKA (7 [3-22] vs. 9 [3-17] days, p = 0.015). Patients with sPESI of ≥ 1 treated with rivaroxaban were hospitalised for a sig-nificantly longer time compared to those with sPESI of 0 treated with rivaroxaban (7 [3-22] vs. 5 [2-11] days, p = 0.00005). CONCLUSIONS Rivaroxaban therapy is a useful therapeutic option in patients with APE. Compared to standard therapy, use of rivaroxaban has been associated with a significant reduction of the duration of hospital stay.

High prevalence of severe coronary artery disease in elderly patients with non-operable chronic thromboembolic pulmonary hypertension referred for balloon pulmonary angioplasty

Introduction Balloon pulmonary angioplasty (BPA) is a new emerging catheter-based alternative treatment option for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Aim To show that all elderly CTEPH patients referred for BPA are at higher risk of obstructive coronary artery disease and that, in daily practice, they should undergo invasive coronary angiography. Material and methods Eleven patients at the age of at least 65 years (6 males, 5 females, 77.2 ±5.9 years) with confirmed non-operable type II or type III CTEPH, considered for BPA, underwent elective coronary angiography. Severe obstructive coronary artery disease (CAD) was diagnosed when stenosis of left main coronary artery ≥ 50% or stenosis of ≥ 70% of epicardial arteries was angiographically confirmed. We also screened for CAD consecutive age- and sex-matched 114 PE survivors (52 males, 62 females, 74.8 ±7.2 years) with excluded CTEPH. Results Severe CAD was more frequent in elderly patients with non-operable type II or type III CTEPH candidates for BPA than in elderly acute PE survivors with excluded CTEPH (54.5% vs. 16.7%, p < 0.01), and therefore elderly CTEPH patients referred for BPA were at higher risk of CAD (OR = 5.9, 95% CI: 1.64–21.46, p = 0.007) when compared to elderly survivors after acute PE with excluded CTEPH. Conclusions All elderly CTEPH patients referred for BPA are at higher risk of severe CAD and should routinely undergo invasive coronary angiography before BPA.

Tricuspid Regurgitation Peak Gradient (TRPG)/Tricuspid Annulus Plane Systolic Excursion (TAPSE) ― A Novel Parameter for Stepwise Echocardiographic Risk Stratification in Normotensive Patients With Acute Pulmonary Embolism ―

BACKGROUND Patients with intermediate-risk acute pulmonary embolism (APE) are a heterogeneous group with an early mortality rate of 2-15%. The tricuspid annulus plane systolic excursion (TAPSE) and tricuspid regurgitation peak gradient (TRPG) can be used for risk stratification, so we analyzed the prognostic value of a new echo parameter (TRPG/TAPSE) for prediction of APE-related 30-day death or need for rescue thrombolysis in initially normotensive APE patients.Methods and Results:The study group consists of 400 non-high-risk APE patients (191 men, age: 63.1±18.9 years) who had undergone echocardiography within the first 24 h of admission. The TRPG/TAPSE parameter was calculated. The clinical endpoint (CE) was a combination of 30-day APE-related death and/or rescue thrombolysis. The CE occurred in 8 (2%) patients. All patients with TAPSE ≥20 mm (n=193, 48.2%) had a good prognosis. Among 206 patients with TAPSE <20 mm, 8 cases of the CE occurred (3.9%). NPV and PPV for TRPG/TAPSE >4.5 were 0.2 and 0.98, respectively. The CE was significantly more frequent in 19 (9.2%) patients with TRPG/TAPSE >4.5 than in 188 (90.8%) with TRPG/TAPSE ≤4.5 (4 (21.1%) vs. 4 (2.1%), P=0.0005). Among normotensive APE patients with TAPSE <20 mm, TRPG/TAPSE >4.5 was associated with 21.1% risk of APE-related death or rescue thrombolysis. CONCLUSIONS TRPG/TAPSE, a novel echocardiographic parameter, may be useful for stepwise echocardiographic risk stratification in normotensive patients with APE, and it identifies patients with a poor prognosis.

Response to Letter to the Editor from Anthanont Pimjai: Emerging Markers of Atherosclerosis Before and After Bariatric Surgery

Dear Dr. Anthanont Pimjai, We have carefully read with great interest your letter to the Editor with comments and concerns about the results of our study [1]. We would like to make some remarks. All women included in our study, both in the study and in the control group, were Caucasian [2]. Therefore, the study group was homogeneous in terms of ethnicity, so no ethnic variations could be observed. However, we agree with you that the available data on the potential influence of adiponectin on cardiovascular disease is rather equivocal. Aung et al. in their meta-analysis (14,063 CVD patients enrolled) showed a strong positive association of adiponectin with cardiovascular mortality (n = 11 studies, overall pooled effect estimate = 1.69 [1.35–2.10]) [3]. That was in accordance with a study by Schondorf et al. as well as our research [2, 4]. Furthermore, it is worth noticing that some studies have suggested that high-molecular-weight adiponectin is a stronger risk factor for cardiovascular diseases than total adiponectin level [5]. In another study, serum adiponectin levels were found to be inversely correlated with intima-media thickness as a marker of carotid atherosclerosis [6]. As Dr Pimjai mentioned before, other adequately powered studies failed to identify adiponectin as a cardiovascular risk factor. Some researchers claim that these contradictory results in this field might be caused by confounding factors, sex and age of the analyzed subjects, different oligomers of adiponectin tested, other methodological issues (various assays: radioimmunoassays or ELISAs), or handling of laboratory samples.[7] We agree with Dr Pimjai that further, well-designed studies are needed to clarify the full relationship between adiponectin and the risk of cardiovascular disease.