Opportunities for improved clinical trial designs in acute respiratory distress syndrome.

The acute respiratory distress syndrome (ARDS) is a common critical illness syndrome with high morbidity and mortality. There are no proven pharmacological therapies for ARDS. The current definition of ARDS is based on shared clinical characteristics but does not capture the heterogeneity in clinical risk factors, imaging characteristics, physiology, timing of onset and trajectory, and biology of the syndrome. There is increasing interest within the ARDS clinical trialist community to design clinical trials that reduce heterogeneity in the trial population. This effort must be balanced with ongoing work to craft an inclusive, global definition of ARDS, with important implications for trial design. Ultimately, the two aims-to design trials that are applicable to the diverse global ARDS population while also advancing opportunities to identify targetable traits-should coexist. In this Personal View, we recommend two primary strategies to improve future ARDS trials: the development of new methods to target treatable traits in clinical trial populations, and improvements in the representativeness of ARDS trials, with the inclusion of global populations. We emphasise that these two strategies are complementary. We also discuss how a proposed expansion of the definition of ARDS could affect the future of clinical trials.

Does kidney function matter in pulmonary thromboembolism management?

Cardiovascular circulation and kidney function are closely interrelated. The impairment of renal function is a well-known hazard of increased mortality and morbidity of patients with heart failure or coronary artery disease. Acute pulmonary embolism (APE) impacts pulmonary and systemic circulation, and can severely impair functions of other organs, including kidneys, as a result of hypoxemia and increased venous pressure. Previous studies indicate that renal dysfunction predicts short- and long-term outcomes and can improve the risk assessment in APE. However, renal function should also be cautiously considered during the diagnostic workup because the contrast-induced nephropathy after computed tomography pulmonary angiography is noticed more frequently in APE. Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare but imminent complication of APE. This condition promotes renal impairment by increasing venous pressure and decreasing glomerular filtration. The renal function improvement and serum creatinine concentration reduction were noted in CTEPH subgroup with glomerular filtration rate ≤ 60 mL/min/1.73 m2 after successful treatment. In this review, we present the essential research results on the kidney function in thromboembolism disease.

A Comparison of GFR Calculated by Cockcroft-Gault vs. MDRD Formula in the Prognostic Assessment of Patients with Acute Pulmonary Embolism.

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.

Ventricular Septal Defect in Delayed Presentation of ST-Elevation Myocardial Infarction (STEMI) Secondary to COVID-19 Pandemic.

Like many other countries at the moment, the United Kingdom (UK) is currently under national lockdown due to the coronavirus disease 2019 (COVID-19) pandemic. An unfortunate consequence of such social isolation measures is that patients with genuine acute medical emergencies may not present to a hospital in a timely manner. We present such a scenario, whereby a patient had a delayed presentation of ST-elevation myocardial infarction (STEMI) due to fear of breaching COVID-19 lockdown rules. As a result of the patient presenting well outside the optimal treatment window, her STEMI was complicated by a severe ventricular septal defect (VSD). We discuss how the COVID-19 pandemic has influenced the nature and management of STEMIs and associated issues.

Optimising clinical trials in acute myocardial infarction complicated by cardiogenic shock: a statement from the 2020 Critical Care Clinical Trialists Workshop.

Acute myocardial infarction complicated by cardiogenic shock (AMICS) is a critical syndrome with a high risk of morbidity and mortality. Current management consists of coronary revascularisation, vasoactive drugs, and circulatory and ventilatory support, which are tailored to patients mainly on the basis of clinicians' experience rather than evidence-based recommendations. For many therapeutic interventions in AMICS, randomised clinical trials have not shown a meaningful survival benefit, and a disproportionately high rate of neutral and negative results has been reported. In this context, an accurate definition of the AMICS syndrome for appropriate patient selection and optimisation of study design are warranted to achieve meaningful results and pave the way for new, evidence-based therapeutic options. In this Position Paper, we provide a statement of priorities and recommendations agreed by a multidisciplinary group of experts at the Critical Care Clinical Trialists Workshop in February, 2020, for the optimisation and harmonisation of clinical trials in AMICS. Implementation of proposed criteria to define the AMICS population-moving beyond a cardio-centric definition to that of a systemic disease-and steps to improve the design of clinical trials could lead to improved outcomes for patients with this life-threatening syndrome.

Defining right ventricular dysfunction by echocardiography in normotensive patients with pulmonary embolism.

INTRODUCTION: Although the prognostic value of various echocardiographic parameters of right ventricular dysfunction (RVD) was reported in normotensive patients with acute pulmonary embolism (PE), there is no generally accepted definition of RVD. OBJECTIVES: The aim of the study was to compare echocardiographic parameters for the prediction of an adverse 30­day outcome and create an optimal definition of RVD.                                     Patients and methods: Echocardiographic parameters including the right ventricular to left ventricular diameter ratio (RV to LV ratio) and tricuspid annular plane systolic excursion (TAPSE) to predict PE­related mortality, hemodynamic collapse, or rescue thrombolysis within the first 30 days were directly compared in 490 normotensive patients with PE. RESULTS: An adverse outcome (AO) was present in 31 patients (6.3%); 8 of them (1.6%) died due to PE. Systolic blood pressure, RV to LV ratio, and TAPSE were independent predictors of AO. The receiver operator characteristic yielded an area under the curve of 0.737 (0.654-0.819; P <0.001) for the RV to LV ratio and 0.75 (0.672-0.828; P <0.001) for TAPSE with regard to an AO. The hazard ratio for AO was 2.5 for the RV to LV ratio of more than 1 (95% CI, 1.2-5.7; P <0.03) and 3.8 for TAPSE of less than 16 mm (95% CI, 1.74-8.11; P = 0.001). A combined RVD criterion (TAPSE <16 mm and RV to LV ratio >1) was present in 60 patients (12%), and showed a positive predictive value of 23.3% with a high negative predictive value of 95.6% regarding an AO (HR, 6.5; 95% CI, 3.2-13.3; P <0.001). CONCLUSIONS: Defining RVD on echocardiography by the RV to LV ratio of more than 1 combined with TAPSE of less than 16 mm identified patients with an increased risk of 30­day PE­related mortality, hemodynamic collapse, or rescue thrombolysis, while patients without this sign had a very good 30­day prognosis.

Cardiovascular care of patients with stroke and high risk of stroke: The need for interdisciplinary action: A consensus report from the European Society of Cardiology Cardiovascular Round Table.

Comprehensive stroke care is an interdisciplinary challenge. Close collaboration of cardiologists and stroke physicians is critical to ensure optimum utilisation of short- and long-term care and preventive measures in patients with stroke. Risk factor management is an important strategy that requires cardiologic involvement for primary and secondary stroke prevention. Treatment of stroke generally is led by stroke physicians, yet cardiologists need to be integrated care providers in stroke units to address all cardiovascular aspects of acute stroke care, including arrhythmia management, blood pressure control, elevated levels of cardiac troponins, valvular disease/endocarditis, and the general management of cardiovascular comorbidities. Despite substantial progress in stroke research and clinical care has been achieved, relevant gaps in clinical evidence remain and cause uncertainties in best practice for treatment and prevention of stroke. The Cardiovascular Round Table of the European Society of Cardiology together with the European Society of Cardiology Council on Stroke in cooperation with the European Stroke Organisation and partners from related scientific societies, regulatory authorities and industry conveyed a two-day workshop to discuss current and emerging concepts and apparent gaps in stroke care, including risk factor management, acute diagnostics, treatments and complications, and operational/logistic issues for health care systems and integrated networks. Joint initiatives of cardiologists and stroke physicians are needed in research and clinical care to target unresolved interdisciplinary problems and to promote the best possible outcomes for patients with stroke.

Increased systemic arterial stiffness in patients with chronic thromboembolic pulmonary hypertension.

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.

Peak systolic velocity of tricuspid annulus is inferior to tricuspid annular plane systolic excursion for 30 days prediction of adverse outcome in acute pulmonary embolism.

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.

"The post-pulmonary syndrome - results of echocardiographic driven follow up after acute pulmonary embolism".

INTRODUCTION: The concept of post Pulmonary Embolism syndrome includes various combinations of functional, haemodynamic or imaging abnormalities in patients after pulmonary embolism (PE). Although residual obstruction of pulmonary vascular bed is suggested to be a major cause of post Pulmonary Embolism syndrome (post-PE syndrome) other cardiopulmonary abnormalities can be responsible for functional impairment. Therefore, we analyzed the frequency of post-PE syndrome and its potential causes. MATERIAL AND METHODS: We report data of consecutive 845 PE survivors (468 F, aged 62 ± 18 yrs) who were anticoagulated, and followed for at least 6 months. All symptomatic subjects at follow up underwent diagnostic workup. RESULTS: 35% (290/845) of PE survivors recovered functionally, while 65% patients reported a decreased exercise tolerance compatible with post-PE syndrome. One hundred and five symptomatic cases were lost to follow up. After diagnostic workup, chronic thromboembolic pulmonary hypertension (CTEPH) was diagnosed in 38 of 450 (8.4%) symptomatic subjects and chronic thromboembolic pulmonary disease (CTED) was diagnosed in 15/450 (3.3%) of them. Chronic heart failure with reduced ejection fraction (EF) was found in 6.9% (31/450) of patients and 154 patients (34.2%) had leftsided diastolic dysfunction. Valve heart disease was detected in 6.2% (28/450), atrial fibrillation in 31/450 (6.9%), Other causes of reduced exercise tolerance include coronary artery disease in 31/450 (6.9%), pulmonary disease 42/450 (9.3%), morbid obesity 15/450 (3.3%), neoplasms 15/450 (3.3%), psychiatric disorders 1%, rheumatoid disease 1%, anemia 1%. CONCLUSIONS: Approximately 65% of PE survivors report functional impairment, despite at least 6 months of anticoagulation. Persistent pulmonary artery thromboemboli resulting in CTEPH or CTED were detected in 7.2% of PE survivors and 11.8% of symptomatic patients. Leftsided diastolic dysfunction was the most prevalent echocardiographic abnormality, and remained the most common cause of functional limitation affected 34.2% of symptomatic cases.

The Prognostic Value of Renal Function in Acute Pulmonary Embolism-A Multi-Centre Cohort Study.

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.

Incomplete echocardiographic recovery at 6 months predicts long-term sequelae after intermediate-risk pulmonary embolism. A post-hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial.

INTRODUCTION: Symptoms and functional limitation are frequently reported by survivors of acute pulmonary embolism (PE). However, current guidelines provide no specific recommendations on which patients should be followed after acute PE, when follow-up should be performed, and which tests it should include. Definition and classification of late PE sequelae are evolving, and their predictors remain to be determined. METHODS: In a post hoc analysis of the Pulmonary Embolism Thrombolysis (PEITHO) trial, we focused on 219 survivors of acute intermediate-risk PE with clinical and echocardiographic follow-up 6 months after randomisation as well as over the long term (median, 3 years after acute PE). The primary outcome was a composite of (1) confirmed chronic thromboembolic pulmonary hypertension (CTEPH) or (2) 'post-PE impairment' (PPEI), defined by echocardiographic findings indicating an intermediate or high probability of pulmonary hypertension along with New York Heart Association functional class II-IV. RESULTS: Confirmed CTEPH or PPEI occurred in 29 (13.2%) patients, (6 with CTEPH and 23 with PPEI). A history of chronic heart failure at baseline and incomplete or absent recovery of echocardiographic parameters at 6 months predicted CTEPH or PPEI at long-term follow-up. CONCLUSIONS: CTEPH or PPEI occurs in almost one out of seven patients after acute intermediate-risk PE. Six-month echocardiographic follow-up may be useful for timely detection of late sequelae.

Prognostic impact of copeptin in pulmonary embolism: a multicentre validation study.

To externally validate the prognostic impact of copeptin, either alone or integrated in risk stratification models, in pulmonary embolism (PE), we performed a post hoc analysis of 843 normotensive PE patients prospectively included in three European cohorts.Within the first 30 days, 21 patients (2.5%, 95% CI 1.5-3.8) had an adverse outcome and 12 (1.4%, 95% CI 0.7-2.5) died due to PE. Patients with copeptin ≥24 pmol·L-1 had a 6.3-fold increased risk for an adverse outcome (95% CI 2.6-15.5, p<0.001) and a 7.6-fold increased risk for PE-related death (95% CI 2.3-25.6, p=0.001). Risk classification according to the 2014 European Society of Cardiology (ESC) guideline algorithm identified 248 intermediate-high-risk patients (29.4%) with 5.6% (95% CI 3.1-9.3) at risk of adverse outcomes. A stepwise biomarker-based risk assessment strategy (based on high-sensitivity troponin T, N-terminal pro-brain natriuretic peptide and copeptin) identified 123 intermediate-high-risk patients (14.6%) with 8.9% (95% CI 4.5-15.4) at risk of adverse outcomes. The identification of patients at higher risk was even better when copeptin was measured on top of the 2014 ESC algorithm in intermediate-high-risk patients (adverse outcome OR 11.1, 95% CI 4.6-27.1, p<0.001; and PE-related death OR 13.5, 95% CI 4.2-43.6, p<0.001; highest risk group versus all other risk groups). This identified 85 patients (10.1%) with 12.9% (95% CI 6.6-22.0) at risk of adverse outcomes and 8.2% (95% CI 3.4-16.2) at risk of PE-related deaths.Copeptin improves risk stratification of normotensive PE patients, especially when identifying patients with an increased risk of an adverse outcome.

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.

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.

Impact of Thrombolytic Therapy on the Long-Term Outcome of Intermediate-Risk Pulmonary Embolism.

BACKGROUND: The long-term effect of thrombolytic treatment of pulmonary embolism (PE) is unknown. OBJECTIVES: This study investigated the long-term prognosis of patients with intermediate-risk PE and the effect of thrombolytic treatment on the persistence of symptoms or the development of late complications. METHODS: The PEITHO (Pulmonary Embolism Thrombolysis) trial was a randomized (1:1) comparison of thrombolysis with tenecteplase versus placebo in normotensive patients with acute PE, right ventricular (RV) dysfunction on imaging, and a positive cardiac troponin test result. Both treatment arms received standard anticoagulation. Long-term follow-up was included in the third protocol amendment; 28 sites randomizing 709 of the 1,006 patients participated. RESULTS: Long-term (median 37.8 months) survival was assessed in 353 of 359 (98.3%) patients in the thrombolysis arm and in 343 of 350 (98.0%) in the placebo arm. Overall mortality rates were 20.3% and 18.0%, respectively (p = 0.43). Between day 30 and long-term follow-up, 65 deaths occurred in the thrombolysis arm and 53 occurred in the placebo arm. At follow-up examination of survivors, persistent dyspnea (mostly mild) or functional limitation was reported by 36.0% versus 30.1% of the patients (p = 0.23). Echocardiography (performed in 144 and 146 patients randomized to thrombolysis and placebo, respectively) did not reveal significant differences in residual pulmonary hypertension or RV dysfunction. Chronic thromboembolic pulmonary hypertension (CTEPH) was confirmed in 4 (2.1%) versus 6 (3.2%) cases (p = 0.79). CONCLUSIONS: Approximately 33% of patients report some degree of persistent functional limitation after intermediate-risk PE, but CTEPH is infrequent. Thrombolytic treatment did not affect long-term mortality rates, and it did not appear to reduce residual dyspnea or RV dysfunction in these patients. (Pulmonary Embolism Thrombolysis study [PEITHO]; NCT00639743).

Age­adjusted plasma D­dimer levels in suspected acute pulmonary embolism: a retrospective, single­center study.

INTRODUCTION The conventional D­dimer threshold (CDD) is characterized by high sensitivity and low specificity in diagnosing acute pulmonary embolism (PE) in older patients. A higher cut­off level for D­dimer has been proposed, aiming at increasing the specificity while maintaining high sensitivity. It is calculated by multiplying the patient's age in years by a coefficient of 10 (YADD10). OBJECTIVES The aim of this study was to validate the clinical value of YADD10 in patients with suspected acute PE and to optimize this threshold to achieve increased specificity paired with high sensitivity. PATIENTS AND METHODS The medical records of 1022 patients with suspected acute PE, hospitalized between the years 2014 and 2016, were retrospectively analyzed. Patients older than 50 years, with complete medical records and good quality of multislice computed tomography (CT) scans were enrolled. The sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of the proposed thresholds were calculated and compared with those of the CCD. The number of computed tomography scans that could have been avoided with higher thresholds was determined. RESULTS The final analysis included 321 patients (176 women; mean age, 74.2 years; range, 51-101 years). Acute PE was confirmed in 135 patients. The sensitivity of CDD was 100%, and specificity-5.4%. The use of the YADD10 and YADD11 thresholds (obtained by multiplying by the coefficients of 10 and 11, respectively) resulted in maintaining high sensitivity, with increased specificity of 8.6% (YADD10) and 12.4% (YADD11). The number of unnecessary CT scans was reduced by 7%. CONCLUSIONS The YADD thresholds are characterized by high sensitivity and increased specificity when compared with CDD, thus allowing for a safe reduction of the number of CT scans. A prospective study should be conducted to validate these results.

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.