bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ambrisentan reverses the prosenescent and anti-autophagic effect of high glucose on human pulmonary artery endothelial cells exposed to hypoxia
Authors: Biondi F , Cabiati M , Sgalippa A , Casieri V , Ghelardoni S , Del Ry S , Madonna R 
Published: October 2024

Abstract

Background
Cardiovascular (CV) comorbidities (systemic hypertension, hyperlipidemia, obesity, diabetes mellitus, peripheral arterial disease, coronary artery disease) are associated with reduced treatment response to specific drugs for group 1 pulmonary arterial hypertension (PAH). Often this epidemiological evidence is the result of misdiagnosis of group 2 PH associated with left heart disease, but it can also be explained as the intrinsic loss of the ability of pulmonary endothelial cells to respond to specific antiremodeling drugs.

Aims
To evaluate the impact of high glucose and hyperosmolar stress on the responsiveness of human pulmonary artery endothelial cells (hPAECs) to the endothelin receptor antagonist ambrisentan in terms of senescence, autophagic activity, viability and expression of some microRNAs involved in pulmonary arterial remodeling.

Methods
We incubated hPAECs with high glucose (HG, 30.5 mM) or high mannitol (HM, 25 mM), with/without ambrisentan (0.02 nM) in normoxia (N) or hypoxia (H) for 24 h and tested them for cell viability (MTT assay), protein and miRNA levels, autophagy and senescence (β-Gal assay) in vitro.

Results
H induced cell death as compared to N (752 ± 44 vs 701 ± 45 Abs units, p = 0.03). H reduced autophagy (Figure 1A-C) and induced senescence (Figure 1D), an effect further potentiated by HG and HM. Treatment with A in N and H significantly reversed the effect of HG but not HM on autophagy (Figure 1A-C) and senescence (Figure 1D). H increased the abundance of antiapoptotic miR124-3, compared to N in vehicle (V)-treated hPAEC (p=0.008) (Figure 2A), and induced a similar effect on antiapoptotic and proliferative miR191-3p, although not statistically significant (Figure 2B). In N, A potentiated the expression of both miR124-3p (p=0.007) and miR191-3p (p=0.02) in HG-treated hPAEC, and only miR191-3p in HM-treated hPAEC (p=0.01). A induced a similar effect on miR191-3p in hPAEC exposed to H+HG (p=0.02), with a non-statistically significant trend on miR124-3p.

Conclusions
In hPAEC exposed to H, A retains its pro-autophagic and antisenescent effects in an in vitro model mimicking diabetes. miR124-3p and miR191-3p may act as biomarkers of disease and treatment response to specific drugs in patients with PAH.Figure 1:autophagy and senescenceFigure 2:miRNA expression
Endarterectomy in CTEPH: hemodynamic improvement and RV-PA coupling
Authors: Garcia A , Martins M , Oliveira C , Raposo M , Abrantes A , Cazeiro D , Gregorio C , Fonseca J , Jorge C , Guimaraes T , Martins S , Lousada N , Pinto F , Placido R 
Published: October 2024

Abstract

Introduction
Pulmonary artery endarterectomy (PAE) remains the gold standard in treating chronic thromboembolic pulmonary hypertension (CTEPH). Reducing the thrombotic burden and mechanical obstruction of the pulmonary artery (PA) leads to significant hemodynamic improvement, allowing for favorable right ventricular (RV) remodeling.

Methods
Single center retrospective study, including 30 pts submitted to PEA over a 7-year period. Hemodynamic assessment was performed by right heart catheterization (RHC) before PEA, immediately after and at 6-month follow-up (FUP). Echocardiographic assessment of RV function was acquired at baseline and 6m FUP. Mean absolute differences were calculated before and after PEA. Differences between groups were assessed with ANOVA analysis and ROC curve analysis allowed us to define a cut-off point in mPAP reduction to predict favorable RV remodeling.

Results
We included 30 pts with a mean age of 57,9 ± 13 years old and slight predominance of female sex (57%). Regarding risk assessment with the 4 strata tool at baseline, 23% of pts were high risk, 20% intermediate high, 27% intermediate low and 6% at low risk.
Pulmonary hemodynamics improved immediately after PEA, as indicated by a mean reduction of 28,3 ±17 mmHg in mPAP; 44,4±27,6mmHg in sPAP; 8±3,4 Wu in PVR and an increase in CO of 0,5±1 l/min. This improvement was sustained at 6-m post PEA assessment, with a mean reduction of 31,5 ±26,7 mmHg in mPAP; 48,3±41,2mmHg in sPAP; 6,3±6,2Wu in PVR and a 0,5±1 l/min increase in CO.
Regarding RV remodeling at 6m post PEA, an increase of 0.15±0.2mm/mmHg in TAPSE/PSAP ratio and 3±2,8cm/s in Tricuspid S’ were recorded. RV/PA uncoupling, defined as TAPSE/PSAP &lt;0,31 mm/mmHg, was evident in 73% of pts at baseline, 25% of which recovered at 6m follow-up. There were no significant differences between groups, according to the 4 strata risk assessment at baseline, regarding pulmonary hemodynamics and RV remodeling.
Through ROC curve analysis, we were able to define a cut-off point of 37mmHg in immediate mPAP post-op reduction to predict RV-RA coupling normalization at 6-m FUP (sensitivity 70%, specificity 89%).

Conclusions
PEA remains a cornerstone of CTEPH treatment. It’s impact on improving pulmonary hemodynamics is immediate and maintained at 6-month FUP. This improvement may be expected regardless of risk assessment at baseline. Reducing RV afterload allows favorable remodeling and an immediate post operative reduction of mPAP &gt; 37mmHg may predict normalization of RV-PA coupling.
EPAS-1 as a potential D-dimer alternative in pulmonary embolism evaluation
Authors: Sahin A T , Icli A , Alsancak Y , Tatar S , Sertdemir A L , Celik M , Akilli H 
Published: October 2024

Abstract

Background and Objectives
We aimed in this study was to determine the changes in EPAS-1 levels, which is a biomarker proven to increase with hypoxia, at the time of diagnosis and after treatment in addition to the laboratory parameters and scoring systems examined at the time of admission in patients with pulmonary thromboembolism.

Methods
Our study included 60 pulmonary embolism patients followed in the Cardiology clinic and 60 control groups with similar demographic characteristics. Laboratory parameters determined at the time of admission were examined. Pulmonary embolism risk and severity scores were applied and EPAS-1 levels were also studied. To determine the response, EPAS-1 levels were checked 3 days later and compared with the control group.

Results
There was no difference between the two groups in terms of demographic characteristics and comorbidities.EPAS-1 levels were found to be higher at the time of diagnosis compared to the control group ((3.6±1.42/1.57±0.45), p&lt;0.001). It showed a statistically significant positive correlation with PESI severity score and risk score in the patient group. EPAS-1 levels were shown to decline with the treatment of the patients and the tendency to decline was different according to the types of treatment. In patients who died, EPAS-1 levels continued to increase despite treatment (p:0.014).

Conclusions
Our study is important in that EPAS-1 levels, which are correlated with scoring systems and other laboratory parameters used in pulmonary embolism patients, can be used as a predictive value in the diagnostic process of the disease and play a complementary role in the evaluation of treatment response.
Intracranial haemorrhage following treatment for pulmonary embolism: analysis of the german nationwide inpatient sample
Authors: Christodoulou K C , Farmakis I T , Mohr K , Valerio L , Muenzel T , Lurz P , Gori T , Uphaus T , Jaegersberg M , Hobohm L , Konstantinides S V , Keller K 
Published: October 2024

Abstract

Background
Intracranial haemorrhage (ICH) can be a life-threatening complication of pulmonary embolism (PE) and its treatment during the acute phase.

Purpose
To characterize patients hospitalized with PE and ICH by identifying risk factors across different treatment groups, and to detect temporal trends in a large nationwide sample.

Methods
The German nationwide inpatient sample was screened for patients admitted with PE during the period 2005-2020. All hospitalizations were stratified based on the occurrence of ICH and accordingly, risk factors for ICH were investigated (source: Research data center [RDC] of the Federal Statistical Office and the Statistical Offices of the federal states, DRG Statistics 2005-2020, own calculations).

Results
Overall, 816,653 hospitalizations were included in the present study; among them, 2516 (0.3%) experienced an ICH event and 84,810 (10.4%) died in-hospital. The annual number of hospitalizations of patients admitted due to PE increased steadily from 38,749 in 2005 to 54,966 in 2020, whereas the incidence of ICH remained, despite annual fluctuations, largely stable over time, both in the entire study population and in the subgroup of patients with severe PE as defined by clinical and haemodynamic parameters (n=270,980 [33.2%]). ICH was overall more frequent after the seventh decade of life but, interestingly, no correlation with age was found amongst patients with severe PE (Figure 1). ICH in hospitalized PE patients was associated with an aggravated comorbidity burden mirrored by a higher Charlson Comorbidity Index (5.0 [interquartile range 4.0-7.0] vs. 4.0 [2.0-5.0], P&lt;0.001). This was mainly driven by the higher prevalence of heart failure (27.3% vs. 19.4%, P&lt;0.001) and acute or chronic kidney disease (27.6% vs. 18.1%, P&lt;0.001) in patients with ICH. In addition, severe PE (OR 3.09 [95% CI 2.84-3.35], P&lt;0.001), acute kidney injury (OR 3.60 [3.09-4.18], P&lt;0.001), and particularly ischaemic stroke (OR 14.64 [12.61-17.00], P&lt;0.001) were identified as independent predictors of ICH by multivariable logistic regressions. Overall, 27% of the ICH cases were related to systemic thrombolysis. In PE patients treated with systemic thrombolysis, age ≥70 years as well as female sex were independent predictors of ICH. Finally, ICH was independently associated with a substantial increase in case-fatality in patients hospitalized with PE (univariate OR: 5.38 [4.97-5.84], P&lt;0.001; multivariable OR: 6.16 [5.64-6.72], P&lt;0.001).

Conclusions
In this healthcare dataset of the German nationwide inpatient sample, the overall incidence of ICH remained low at 0.3% over the 15-year study period. Severe PE, age, comorbidity burden, kidney disease, heart failure and ischaemic stroke were independent risk factors for ICH.
The role of comorbidities for hospital outcome of patients with severe acute pulmonary embolism treated with thrombolytic therapy
Authors: Ruzicic D R , Dzudovic D Z B , Subotic S B , Salinger S S , Mitrovic M B , Kos K L J , Benic B M , Jevtic J E , Svircev S M , Mitevska M I , Bozovic B B , Neskovic N A , Obradovic O S 
Published: October 2024

Abstract

Background
The association between the outcome of severe acute pulmonary embolism treated with thrombolytic therapy and the presence of common comorbidities is fairly known.

Methodology
In this study we investigated the influence of common comorbidities (arterial hypertension, atrial fibrillation, heart failure, coronary disease, diabetes mellitus, active malignant disease, chronic obstructive lung disease, chronic renal failure, anemia and previous stroke) to hospital mortality and the composite of major and clinically relevant non-major bleeding at 7 days from hospital admission in patients with severe acute PE treated with thrombolytic therapy enrolled in the Regional PE Registry from the 4 west-Balkan countries. Univariate and multivariable regression analysis (adjusted to age and the presence of arterial hypotension – systolic blood pressure below 90 mmHg) was used to establish association between comorbidities and hospital outcome of acute PE treated with thrombolysis.

Results
2068 patients enrolled with computed tomography pulmonary angiography proven acute, symptomatic PE, and of them 645 patients had features of intermediate-high PE (right ventricle dysfunction with positive biomarkers without severe hypotension) and 283 patients had high-risk PE with arterial hypotension. Of them, 394 (42.5%) were treated with thrombolytic therapy (245 with intermediate-high and 149 with high-risk PE). Overall hospital mortality was 17.0% and the composite of major and clinically relevant non-major bleeding at 7 days was 17.5% (11.2% was major bleeding). Among all tested comorbidities, only 3-staged renal failure (OR 3.56, 95%CI 1.78-7.15, p&lt;0.001 for creatinine clearance 30-59 ml/min compare to clearance ≥ 60 ml/min; and OR 6.01, 95%CI 2.35-15.37, p&lt;0.001 for creatinine clearance &lt;30 ml/min versus ≥ 60 ml/min), and the presence of either paroxysmal or chronic atrial fibrillation had significant higher risk for hospital mortality adjusted to age and the presence of arterial systolic hypotension (OR 2.11, 95% 1.03-4.29, p=0.04). Between all presented comorbidities only the presence of diabetes mellitus type 2 was independently associated with the higher risk for bleeding on thrombolytic therapy OR adjusted to age 2.03, 95%CI 1.126-3.659, p=0.019.

Conclusion
Creatinine clearance and atrial fibrillation were the independent predictors of hospital death and diabetes mellitus type 2 for bleeding in patients with severe acute PE who were treated with thrombolysis.
Prognostic impact of the tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure ratio in acute pulmonary embolism
Authors: Kultursay B , Keskin B , Tanyeri S , Kulahcioglu S , Hakgor A , Mutlu D , Bulu C , Tokgoz H C , Yucel E , Sekban A , Sirma D , Karagoz A , Tanboga I H , Ozdemir N , Kaymaz C 
Published: October 2024

Abstract

Background
Currently available risk stratification models for acute pulmonary embolism (PE) include hemodynamic status, cardiac biomarkers, right ventricle (RV) dysfunction on imaging, and clinical scores. Focusing on length-tension relationship of the ventricle might have a superior predictive capability over RV dysfunction in terms of mortality and classification of patients with acute PE. In this study, our hypothesis suggests that tricuspid annular plane systolic excursion (TAPSE)/systolic pulmonary artery pressure (sPAP) ratio has superior predictive capability for in-hospital mortality in patients with acute PE compared to TAPSE or sPAP as distinct measures.

Methods
This single-center study comprised retrospectively evaluated 703 patients referred to our tertiary cardiovascular center with acute PE. We divided patients into quartiles by TAPSE/sPAP ratio. Different models were developed to quantify the predictive relationship between in-hospital death and echocardiographic measurements. A base model was created with variables including risk status and RV/LV ratio &gt;1. Then, to evaluate the predictive contribution of each measurement; TAPSE/sPAP, TAPSE, and sPAP were sequentially added to the base model. After that, the performance of each model was evaluated.

Results
Predictive and discriminative power was the highest in model containing TAPSE/sPAP. There was still a significant inverse association between TAPSE/sPAP and risk of in-hospital death even after adjusting by risk status and RV/LV ratio &gt;1. ROC curve analysis for TAPSE/sPAP revealed the best cut-off value as 0.34.

Conclusion
The outcomes of our study reveals that the ratio of TAPSE/sPAP serves as a more potent predictor of mortality than either of the two measurements taken separately. The interpretation and utilization of the TAPSE/sPAP cut-off value in acute PE can assist in identifying patients at risk of deterioration and guide the consideration of more intensive treatment options across all risk groups.
Efficacy and safety of reduced-dose and slow-infusion intravenous alteplase regimen in patients with acute pulmonary embolism at intermediate-high-risk
Authors: Kultursay B , Keskin B , Sekban A , Hakgor A , Tokgoz H C , Tanyeri S , Sirma D , Bulus C , Karagoz A , Tanboga I H , Kulahcioglu S , Ozdemir N , Kaymaz C 
Published: October 2024

Abstract

Background
In patients with intermediate-high-risk (IHR) pulmonary embolism (PE), full-dose systemic thrombolytic treatment (STT) has been documented to lower the risk of hemodynamic decompensation and mortality, at the expense of an elevated risk of life-threatening bleeding. In this study, we aimed to evaluate the safety of reduced-dose STT regimen while maintaining effective reperfusion.

Methods
This single-center study comprised 124 retrospectively evaluated patients (female 58.9 % and mean age 55.4+15.8 years) diagnosed with acute PE at IHR status in accordance with European Society of Cardiology (ESC) 2019 acute PE guidelines in whom intravenous (i.v.) alteplase treatments were utilized. Patients fulfilling at least one of the following criteria have been included in the study: systolic blood pressure ≤ 110 mm Hg, heart rate &gt; 100 bpm, SaO2 &lt; 90 % on room air, respiratory rate &gt; 20 breaths per minute, or serum lactate &gt; 2 mmol/L. Exclusion criteria were any contraindication for STT and symptom onset &gt; 14 days. Standard protocol for initial STT was i.v. infusion of alteplase of 25 mg over 4-6 hours. After completion of the infusion, a second STT in the same manner if one of the following criteria were present; heart rate &gt; 100 bpm, SaO2 &lt; 90 % or signs of organ hypoperfusion.

Results
Syncope and concomitant deep vein thrombosis were documented in 27.4 % and 49.2 % of patients, respectively. Baseline vital measures were as follows; heart rate: 112 +16.6 bpm, systolic blood pressure: 123+14.9 mm Hg, SaO2: 89 % (85-93), serum lactate 2.35 (1.6-2.9) mmol/L. Median alteplase dose and infusion duration were 50 (25-50) mg and 6 (4-10) hours, respectively. There were significant improvements in clinical parameters, pulmonary thrombus burden, pressure strain and right ventricular size and function as assessed by computed tomography and echocardiography (p&lt; 0.001 for all). Minor and major bleeding events occurred in 3.2 % and 4.8 % of patients, respectively. One major bleed was due to cerebellar hemorrhage, but did not require surgery and patient was discharged without sequela. There were 6 (4.8 %) in-hospital deaths in which 2 were attributed to major hemorrhages and 4 due to hemodynamic decompensation.

Conclusion
In patients with acute IHR PE, reduced-dose and slow-infusion i.v. alteplase regimen seems to be a clinically relevant and safe reperfusion alternative to full-dose STT protocols associated with well-known major bleeding risks.
Recent secular trends of catheter-directed therapy for treatment of pulmonary embolism: a retrospective cohort study based on German national data
Authors: Oettinger V , Von Zur Muehlen C , Hilgendorf I , Wolf D , Rilinger J , Gauchel N , Maier A , Wessinger M , Kaier K , Westermann D , Olivier C 
Published: October 2024

Abstract

Background
Various approaches exist for treatment of pulmonary embolism, including systemic lysis, catheter-directed therapy, or anticoagulation.

Purpose
This study aimed to describe recent secular trends of treatment strategies for patients with pulmonary embolism.

Methods
Data were interrogated from the Research Data Centre of the German Federal Statistical Office by ICD- and OPS-codes. 800,119 patients with pulmonary embolism, who were treated in German hospitals between 2007 and 2021, were analyzed and grouped according to the therapeutic strategy: no lysis or intervention, systemic lysis, ultrasound-assisted thrombolysis, catheter-directed lysis without ultrasound, retriever system, other transluminal thrombus removal, or surgical thrombectomy. In-hospital outcomes were investigated with focus on the last 8 years.

Results
Of all patients examined, 37,885 were treated with systemic lysis, 1,383 with ultrasound-assisted thrombolysis, 2,520 with catheter-directed lysis without ultrasound, 181 with a retriever system, 695 with other transluminal thrombus removal, and 1,037 with surgical thrombectomy. There was an increase in all catheter-directed therapies between 2007 and 2021 (from 102 to 735 procedures per year) with more than twice as many procedures from 2019 to 2021 (from 343 to 735 procedures). Between 2014 and 2021, 453,893 patients with main diagnosis of pulmonary embolism were included in the analysis. Mean age was 58.4-68.1 years in the observed groups. 42.5-52.2% were female. Highest rates of cor pulmonale were observed in patients undergoing surgical thrombectomy (87.7%) and systemic lysis (80.1%), which also applied to shock (26.2% and 25.7%), while both rates were lowest in patients without lysis or intervention (cor pulmonale: 25.4%, shock: 1.8%). The overall in-hospital mortality rate was 8.3%, ranging between 6.5% in the ultrasound-assisted thrombolysis group and 38.4% in the systemic lysis group. In catheter-directed therapies, the rate of major bleeding (&gt;5 units of red blood cells) was 4.9%, ranging from 3.1% for catheter-directed lysis without ultrasound to 10.1% for other transluminal thrombus removal. The rate of intracerebral bleeding was 1.4%, with 0.0% for ultrasound-assisted thrombolysis and 4.4% for treatment with a retriever system.

Conclusion
In recent years, the use of catheter-directed therapy for pulmonary embolism has steadily increased. Rates of in-hospital major bleeding events and intracerebral bleeding were low.
Types of pulmonary hypertension and prognosis in COVID-19: 18-months analysis of BNP-PL national database
Authors: Mamzer A , Waligora M , Kurzyna M , Mroczek E , Mularek-Kubzdela T , Pruszczyk P , Gasior M , Lewicka E , Karasek D , Kusmierczyk-Droszcz B , Mizia-Stec K , Ptaszynska K , Jachec W , Kopec G , Kasprzak J D 
Published: October 2024

Abstract

Introduction
The COVID-19 pandemic significantly increased mortality in the group of patients (pts) with pulmonary hypertension (PH). However, there is no data whether specific types of this disease, such as PAH associated with connective tissue diseases, were more likely to have a poor prognosis.

Aim
To assess mortality in the course of COVID-19 among pts diagnosed with PH, treated under the Polish ministry therapeutic program and registered in the national BNP-PL database, according to the type of PH.

Methods
We analyzed the records of the complete population of Polish pts treated under the National Drug Program of PH (PAH and CTEPH) and registered in the national database of BNP-PL from 01 March 2020 to 31 August 2022. The clinical severity of COVID-19 course and mortality were reviewed. Clinical characteristics of infected and deceased patients were compared in relation to the type of PH.

Results
The analysis included 143 pts with SARS-CoV-2 infection (mean age 61 ± 15 years; 60% female). Mortality rate was 24% (34/143, including 20 out-of-hospital deaths) vs. 2.6% for estimated in the general population. The highest mortality was observed in the group of pts with idiopathic PAH (33%), slightly lower among pts with connective tissue diseases [CTD] (29%). Patients with congenital heart diseases had a fairly good prognosis [CHD] (81% recovered), and the best survival was recorded in those with CTEPH (84%). CTD and IPAH were found to represent "high-risk" subset with mortality risk ~ 32% vs. ~ 17% in others (p=0.032). Etiologic categories had significant trend for different COVID-19 outcomes according to chi2 test for trend (p=0.039).

Conclusions
The SARS-CoV-2 infection in pulmonary hypertension pts was related to high mortality, with pts with IPAH had the worst prognosis, folloved by pts with CTD who might already have had lung involvement. Interestingly, the best survival was recorded in one of the oldest group - patients with CTEPH. This may be related to the chronic anticoagulant treatment used in this group, as significant disorders of coagulation pathways have been observed in SARS-CoV-2 infection.