bluuebunny/crossref_metadata_2025_split huggingface dataset:
External validation of PE-SARD bleeding score for early major bleeding in patients with acute pulmonary embolism: Insight from the COMMAND VTE Registry-2
Authors: Nishimoto Y , Chatani R , Kaneda K , Ikeda N , Kobayashi Y , Ikeda S , Kim K , Takase T , Tsuji S , Oi M , Takada T , Otsui K , Watanabe T , Yamada T , Yamashita Y 
Published: November 2023

Abstract

Background/Introduction
The current guidelines and existing bleeding risk scores focus on assessing the risk of anticoagulant-related bleeding in patients with pulmonary embolism (PE) who are candidates for extended anticoagulation therapy. However, there is no consensus on the risk of bleeding in the acute phase. The Syncope, Anemia, Renal Dysfunction (PE-SARD) bleeding score has been developed to predict early major bleeding in acute PE patients. However, the score has not yet been externally validated.

Purpose
The present study aimed to externally validate the PE-SARD bleeding score, using a large-scale multicenter observational database of patients with venous thromboembolism (VTE).

Methods
The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 2722 patients with PE who received anticoagulation therapy during the acute phase and had a calculated PE-SARD bleeding score. The eligible patients were classified into three groups: high-risk group with a PE-SARD score &gt;2.5 points, intermediate-risk group with a score of 1–2.5 points, and low-risk group with a score of 0 point. The discriminatory and calibration ability of the PE-SARD score for 30-day major bleeding were assessed by calculating the area under the receiver operating characteristic curve and creating a calibration plot, respectively.

Results
The high-risk group accounted for 537 patients (20%), intermediate-risk group for 1381 (51%), and low-risk group for 804 (30%). The proportion of thrombolysis use did not significantly differ across the groups. Among the patients who received direct oral anticoagulants (DOACs), the proportion of high-dose DOAC initiation was highest (54%) in the low-risk group and lowest in the high-risk group (29%). During the first 30 days of anticoagulation therapy, major bleeding occurred in 118 patients. The cumulative 30-day incidence of major bleeding substantially increased in the higher risk categories by the PE-SARD bleeding score (high-risk group: 8.2% [95% CI, 6.2%–10.9%], intermediate-risk group: 4.5% [95% CI, 3.5%–5.8%], and low-risk group: 1.8% [95% CI, 1.0%–3.0%], long-rank P&lt;0.001). The discriminating power of the score was modest with a C-statistic of 0.65 (95%CI 0.61–0.70). Based on the calibration plot, the PE-SARD bleeding score was well calibrated. A sensitivity analysis excluding 275 outpatients showed similar results.

Conclusions
The risks of 30-day major bleeding in patients with PE substantially increased in the higher risk categories by using the PE-SARD bleeding score. The score is potentially helpful for management of anticoagulation therapy in the acute phase.The Kaplan-Meier curves
Different impact of each score component in the simplified PESI score on acute mortality of patients with pulmonary embolism in the era of direct oral anticoagulant
Authors: Nishikawa R N , Kaneda K K , Chatani R C , Nishimoto Y N , Ikeda N I , Kobayashi Y K , Ikeda S I , Kim K K , Takase T T , Tsuji S T , Oi M O , Takada T T , Otsui K O , Yamashita Y Y 
Published: November 2023

Abstract

Background
The simplified pulmonary embolism severity index (sPESI) score could help the risk stratification of acute mortality in patients with pulmonary embolism (PE) including identification of low-risk patients for outpatient treatment. The sPESI score consisted of six components such as age, history of cancer, history of chronic cardiopulmonary disease, heart rate, systolic blood pressure (sBP), and O2 saturation. However, the prognostic impact of each score component on acute mortality has not been fully evaluated in the era of direct oral anticoagulant (DOAC).

Methods
The COMMAND VTE Registry-2 is a multicenter registry enrolling 5,197 consecutive acute symptomatic venous thromboembolism (VTE) patients among 31 centers in Japan between January 2015 and August 2020. In the current study, we evaluated 927 PE patients with the sPESI score 1, and investigated the impact of each score component on acute mortality and detailed causes of deaths.

Results
The distribution of score components of sPESI score were as follows; 80 years or older: 128 patients (14%), history of cancer: 353 patients (38%), history of chronic cardiopulmonary disease: 91 patients (9.9%), heart rate over 110 bpm: 72 patients (7.8%), sBP under 100 mmHg: 18 patients (2.0%), and O2 saturation under 90%: 258 patients (28%). Among the current study population, 736 patients (79%) developed PE out of hospital, and a majority of them (83%) admitted to the hospital with a median length of hospital stay of 14 days. The cumulative 30-day incidence of all-cause death was 2.1%, and the proportions of mortality varied widely depending on different score component of the sPESI (80 years or older: 0.8%, history of cancer: 4.6%, history of chronic cardiopulmonary disease: 1.1%, heart rate over 110 bpm: 0%, sBP under 100 mmHg: 0%, and O2 saturation under 90%: 0.4%). Among all-cause death events, PE-related deaths accounted 1 in patients with history of cancer, 1 in those with history of chronic cardiopulmonary disease, and 1 in those with O2 saturation under 90%.

Conclusions
The risk of acute mortality in patients with sPESI score 1 was relatively low in the era of DOAC, although that could vary widely according to each score component of the sPESI score, which could be useful for the further risk stratification among these patients.
Acute infections and inflammatory biomarkers in patients with acute pulmonary embolism
Authors: Eggers A , Hafian A , Lerchbaumer M , Hasenfus G , Lankeit M , Ebner M 
Published: November 2023

Abstract

Background
Although pneumonia is considered a common complication of acute pulmonary embolism (PE), the true incidence of infections after PE and the effect of infections on patient outcome are insufficiently studied.

Purpose
To investigate incidence and prognostic impact of acute infections and inflammatory biomarkers in patients with acute PE.

Methods
Consecutive PE patients enrolled in a prospective single-centre registry between 09/2008 and 02/2019 were studied. We excluded patients with (1) missing C-reactive protein (CRP) measurements at the time of PE diagnosis, (2) cardiopulmonary resuscitation as the presenting symptom, and (3) other acute cardiopulmonary or infectious disease responsible for the clinical presentation. We evaluated the incidence and impact of infections requiring antibiotic treatment and of inflammatory biomarkers (CRP and procalcitonin [PCT]) on the primary study outcome (hemodynamic insufficiency or in-hospital all-cause death) and the duration of the in-hospital stay.

Results
We analysed data from 749 patients (age 69 [interquartile range (IQR) 56-78] years). The primary study outcome occurred in 65 (8.7%) patients. Of 26 (3.4%) patients who died during the in-hospital stay, 17 (65.4%) deaths were due to PE and 6 (23.1%) due to infections.
During the first 7 days after PE 347 (46.3%) patients required antibiotic treatment; in 79.6% due to pneumonia (Figure). On multivariate logistic regression analyses, antibiotic treatment increased the risk for the primary outcome with an OR of 3.12 (95% confidence interval [CI] 1.70-5.74), similar to an increase in one risk class of the ESC 2019 risk stratification algorithm (OR 3.45 [95% CI 2.24-5.30]). Furthermore, patients requiring antibiotic treatment had a longer duration of in-hospital stay compared to patients with no antibiotic treatment (11.0 vs. 7.0 days, p&lt;0.001).
At presentation, the majority of patients (86.4%) had CRP elevations above the upper limit of normal (median 33.5 [IQR 11.4-71.2] mg/l) and 34.2% had elevated PCT levels (median 0.05 [IQR 0.03-0.10] µg/l). CRP &gt;124 mg/l and PCT &gt;0.25 µg/l predicted the main study outcome with &gt;90% specificity and odds ratios (OR) of 4.64 (95% CI 2.52-8.21) and 6.88 (95% CI 3.48-13.59), respectively. Furthermore, the predictive value associated with elevated inflammatory markers was independent of established risk factors for early mortality such as elevated troponin and the simplified Pulmonary Embolism Severity Index (sPESI).

Conclusion
Clinically relevant infections requiring antibiotic treatment occurred in almost half of patients with acute PE and carried a similar prognostic effect as an increase in one risk class of the ESC 2019 risk stratification algorithm. Furthermore, elevated levels of CRP and PCT were independent predictors of adverse outcome.Indications for antibiotic treatment
Large-bore mechanical thrombectomy for intermediate- and high-risk pulmonary embolism: interim outcomes from the European cohort of the FLASH registry
Authors: Mahfoud F 
Published: November 2023

Abstract

Background/Introduction
Mechanical thrombectomy is utilized for the treatment of acute pulmonary embolism (PE), but reported outcomes are limited in the European patient population.

Purpose
To report interim results from the European cohort of a large, prospective all-comer registry of mechanical thrombectomy for PE treatment.

Methods
The FLASH registry is a multinational, prospective, observational study of safety and effectiveness outcomes for PE treatment using a large-bore mechanical thrombectomy system. FLASH is currently enrolling up to 200 patients in Europe. The primary endpoint is a composite of Major Adverse Events (MAEs) within 48 hours, including device-related deaths, major bleeding, and intraprocedural AEs. Additional assessments include invasive hemodynamics, hospital resource usage, and dyspnea improvement.

Results
Interim results through 48 hours post-thrombectomy are presented for the first 29 patients enrolled in the European cohort across 4 institutions. Mean patient age was 64.9±14.5 years, 51.7% of patients were male, 10.3% were contraindicated for thrombolysis, 51.7% had concomitant deep vein thrombosis, and 79.3% had centrally located thrombus involving one or both main pulmonary arteries. Per ESC guidelines, 58.6% of patients were classified as high-risk. The remaining 41.4% of patients were classified as intermediate-risk, with 31.0% being intermediate-high-risk.
Pre-thrombectomy, the median RV/LV ratio from a composite of computed tomography and echocardiography was 1.31 [IQR: 1.08-1.44], and 38.9% of patients who had cardiac index (CI) measured were in cardiogenic shock (CI ≤2 L/min/m²).
Procedural characteristics included a median thrombectomy time of 39 minutes [IQR: 26-49]. Extracorporeal membrane oxygenation was used in 6.9% of patients. Post-thrombectomy, the median length of stay in the intensive care unit (ICU) was 1 overnight [IQR: 0-2], and 48.1% of patients required no overnight ICU stay. In addition, hemodynamic variables, vitals, dyspnea symptoms, and reliance on supplemental oxygen all improved significantly post-thrombectomy (Table 1).
Acute safety and mortality outcomes were highly favorable following the procedure (Table 2). All patients survived through 48 hours post-thrombectomy. There were no MAEs (0%), no major access site complications (0%), and no device-related Serious AEs (0%) through 48-hour follow-up.

Conclusions
Interim results from the first 29 patients in the European cohort of the FLASH registry suggest that large-bore mechanical thrombectomy can be safely performed in both intermediate- and high-risk PE patients, with no MAEs or mortalities observed through 48 hours. Significant improvements observed in multiple hemodynamic and dyspnea-related variables further suggest that thrombectomy can offer effective reperfusion treatment for acute PE.
Associated factors and clinical implications of dynamic changes in late gadolinium enhancement after acute myocarditis
Authors: Bohbot Y , Sanguineti F , Renard C , Hovasse T , Limouzineau I , Unterseeh T , Di Lena C , Boukefoussa W , Tawa C , Duhamel S , Garot P , Tribouilloy C , Garot J 
Published: November 2023

Abstract

Background
Although follow-up cardiac magnetic resonance (CMR) is often performed after acute myocarditis (AM), the prognostic implications of dynamic changes in late gadolinium enhancement (LGE) are unknown.

Purposes
To determine the prognostic implications of dynamic LGE changes after acute AM.

Methods
In a two-centre study, 204 consecutive hemodynamically stable patients (mean age 35±16 years, 78.9% males) with a CMR-based diagnosis of AM were included and underwent repeat CMR 3-12 months after diagnosis. Quantitative LGE was expressed as percent of left ventricular (LV) myocardium. The primary endpoint was the occurrence of major adverse cardiac events (MACE) at median 7.3[IQR:5.7-8.7] years.

Results
Compared to index CMR, there was an increase in LV ejection fraction (EF) (59% vs. 55%,p&lt;0.001) and a decrease in LGE extent (7.6% vs. 12.0%,p&lt;0.001) at follow-up (mean 5.7±2.6 months after index CMR). LGE persisted in 175 patients at follow-up (85.8%). LGE decreased by ≥50% from baseline in 94 patients (46%), by &lt;50% in 86(42%) and increased in 24(12%). Female gender (OR[95%CI]=3.27[1.17-9.12],p=0.023), low baseline LVEF (OR[95%CI]=0.93[0.88-0.98] per %,p=0.010) and LGE involving both septal and lateral walls (OR[95%CI]=4.64[1.77-12.17],p=0.002) were independently associated with increased LGE. By multivariate Cox analysis, only acute heart failure at inclusion (HR[95%CI]=3.11[1.02-9.20],p=0.044), baseline LVEF (HR[95%CI]=0.95[0.89-0.99] per %,p=0.028), a &lt;50% LGE decrease (HR[95%CI]=2.17[1.23-3.88],p=0.021) and an increase in LGE (HR[95%CI]=4.12[1.47-11.52],p=0.004) were significantly associated with MACE.

Conclusion
After AM, LGE persists at 6 months in the vast majority of patients but tends to decrease. A &lt;50% decrease or an increase in LGE are associated with MACE, indicating that follow-up CMR is relevant for risk stratification.SUMMARY OF THE STUDY
Effectiveness and safety of catheter-directed thrombolysis for pulmonary embolism in key patient subgroups: results of an individual patient level analysis
Authors: Fumagalli R , Fuerbringer Schwarz A , Catalani F , Farmakis I , Kucher N , Konstantinides S , Barco S 
Published: November 2023

Abstract

Background
The effectiveness of catheter-directed thrombolysis (CDT) for acute pulmonary embolism (PE) has been rarely investigated in subgroups of patients at a higher risk of complications. Furthermore, this group of patients has been excluded from prior and ongoing phase 3 trials with CDT.

Purpose
To assess the efficacy and safety of catheter-directed thrombolysis for pulmonary embolism among specific patient subpopulations.

Material and methods
We conducted an individual patient-level analysis of patient data from 16 cohort studies and randomized trials of CDT for intermediate- and high-risk acute PE. Studies were identified on the basis of a systematic review of the literature. We focused on early clinical outcomes, including haemodynamic decompensation, intracranial bleeding, major bleeding, and death, as well as on the changes in the mean pulmonary artery pressure (mPAP) before and after CDT. We predefined three subgroups of at-risk patients: (i) older age (i.e. ≥75 years), (ii) active cancer, and (iii) surgery in the prior 4 weeks.

Results
We studied 1244 patients, of whom 586 (47.1%) were women. The median age was 61 (Q1-Q3; 50-71) years. There were 202 (16.3% of total available) patients aged 75 years or older, 101 (10%) with active cancer, and 108 (14.8%) with prior surgery. A total of 946 (89.3%) patients had intermediate-risk PE, and 113 (10.7%) were classified in the high-risk group. Patients aged ≥75 years more frequently suffered haemodynamic decompensation (7.5% vs 1.6% aged &lt;75 years; p&lt; 0.001), major bleeding (12.7% vs 4.5%; p&lt;0.001), and death (9.2% vs 2.2%; p&lt;0.001); Table 1. In a multivariable logistic regression model, age remained associated with death, major bleeding, and haemodynamic decompensation after adjustment for a key prognostic factor (high-risk PE). The same, except for decompensation, was observed after conditioning for sex, high-risk PE, and cancer status. Patients with active cancer showed a tendency to a higher 30-day case fatality when compared with patients with no active cancer, without reaching statistical significance; Table 1. Recent surgery did not appear to influence the outcome rate in this cohort. No differences were found among the three subgroups regarding the reduction of the mPAP following CDT ; Table 2.

Conclusions
Our results point to age as a strong predictor of early mortality and decompensation in patients undergoing CDT, even after adjusting for the higher rate of high-risk PE in the elderly. The clinical net benefit of CDT in the elderly when accounting for bleeding and the risk of haemodynamic decompensation remains unclear.Efficacy and safety outcomes of CDTmPAP values before and after CDT
Macitentan tadalafil Fixed Dose Combination (FDC) in treatment-naive and prior monotherapy patients with Pulmonary Arterial Hypertension (PAH): insights from A DUE
Authors: Gruenig E , Jansa P , Fan F , Friberg M , Lassen C , Pannaux M , Rofael H , Chin K 
Published: November 2023

Abstract

Background
Combination therapy is recommended for the management of pulmonary arterial hypertension (PAH). The A DUE study showed that M/T FDC, a fixed dose combination (FDC) of the endothelin receptor antagonist (ERA) macitentan 10mg (M) and the phosphodiesterase type 5 inhibitor (PDE5i) tadalafil 40mg (T), led to a clinically relevant improvement in pulmonary vascular resistance (PVR) vs macitentan and tadalafil monotherapies in PAH patients. A clinically meaningful trend for improvement in 6-minute walk distance (6MWD) in favor of M/T FDC vs macitentan and tadalafil was observed.

Purpose
Here we analysed the effect of M/T FDC in the subgroups of treatment-naïve and prior monotherapy patients.

Methods
In A DUE 187 adult PAH patients in WHO functional class II / III were randomised 2:1:1 to M/T FDC, macitentan or tadalafil if treatment-naïve, 2:1 to M/T FDC or macitentan if on prior ERA, and 2:1 to M/T FDC or tadalafil if on prior PDE5i. The treatment effect of M/T FDC vs macitentan and M/T FDC vs tadalafil was calculated using ANCOVA models for PVR (geometric mean ratios [95% CL]) and for 6MWD (mean change [95% CL]) in treatment-naïve patients and in patients on prior monotherapy (ERA or PDE5i) at randomisation.

Results
Treatment effects for M/T FDC versus macitentan and versus tadalafil on the change in PVR and 6MWD are reported in the table for each subgroup, along with those for the overall population. The safety profile of M/T FDC was in line with the safety profiles of macitentan and tadalafil.

Conclusions
In A DUE, the effect of M/T FDC vs both monotherapies on PVR and 6MWD in treatment-naïve and prior ERA/PDE5i patients was consistent with that observed in the overall population.
Tricuspid regurgitation in pulmonary arterial hypertension: relations with right ventricular function and prognosis
Authors: Yoshida K , Wezenbeek J V , Wessels J N , Abe K , De Man F S , Noordegraaf A V , Bogaard H J 
Published: November 2023

Abstract

Background
Pulmonary arterial hypertension (PAH) is a devastating disease characterized by progressive pulmonary vascular remodeling and increased pulmonary vascular resistance (PVR), subsequent right ventricular (RV) failure and premature death (1). Progressive RV overload leads to RV dilatation, which in turn induces tethering of the tricuspid valve and functional valvular regurgitation (2,3). As such, severity and the progression of tricuspid regurgitation (TR), as evaluated by echocardiographic qualitative analysis, are reported to associate with a poor prognosis in PAH (4,5). However, it has remained unclear to what extent the severity of TR directly impacts RV hemodynamics and prognosis of PAH patients.

Purpose
This study aimed to explore the consequences of TR for RV function and prognosis in PAH using a volumetric analysis by cardiac magnetic resonance (CMR).

Methods
92 PAH patients, mean pulmonary arterial pressure (mPAP) ≥25 mmHg and pulmonary artery wedge pressure ≤15 mmHg, with available CMR data from January 1st 2010 to August 31st 2021 were included in this study. TR volume was calculated as the difference between the stroke volume (SV) of RV and pulmonary artery (PA). TR severity was graded as no or mild (TR&lt;30 mL), moderate (30≤TR&lt;45 mL) and severe (TR≤45 mL). Hemodynamic assessment was performed by right heart catheterization. Event free survival was estimated from the time of the CMR scan to cardiopulmonary death or lung transplantation.

Results
In the studied cohort, 74% of PAH patients had no or mild TR, 16% had moderate TR, and 10% had severe TR (Table 1). A greater TR volume was characterized by increased NT-proBNP, increased mPAP, PVR and mean right atrial pressure (mRAP), and increased RV volume. Additionally, RVSV was higher while PASV was lower. There was no difference in RV ejection fraction (RVEF). Pearson correlation analysis showed a good correlation between TR volume and parameters of PAH severity, such as NT-proBNP, RV end-systolic volume (RVESV), mRAP and cardiac index (CI) (Figure 1). ROC curves analysis revealed that the optimal cut-off value of TR volume was 30 mL. Kaplan-Meier survival analysis demonstrated that TR volume ≥30 mL was strongly associated with a poor event free survival (Figure 2).

Conclusion
26% of PAH patients had a TR volume 30 ≥mL. TR severity showed a good correlation with PAH disease severity. TR volume 30 ≥mL, i.e. moderate or severe TR, was strongly associated with a poor prognosis in PAH patients.TableFigure
The prognostic value of left ventricular entropy derived from native T1 mapping in patients with hypertrophic cardiomyopathy
Authors: Wang J , Zhang J Q , Pu L T , Gkoutos G V , Han Y C , Chen Y C 
Published: November 2023

Abstract

Background
The prognostic value of Left ventricular (LV) entropy in hypertrophic cardiomyopathy (HCM) is unclear.

Objectives
This study aimed to assess the prognostic value of LV entropy from T1 mapping in HCM.

Methods
In this prospective study, 748 participants with HCM, who underwent cardiovascular MRI, were consecutively enrolled. LV entropy was quantified by native T1 mapping to estimate tissue heterogeneity. A multivariable Cox proportional hazards regression was performed to identify potential associations of LV entropy with sudden cardiac death (SCD) and cardiovascular death (CVD).

Results
Among the 748 participants (mean age, 51 ± 14.2 years; 454 men), 40 (5.3%) experienced SCD, and 65 (8.7%) experienced CVD during a median follow-up of 43 months. Participants with increased LV entropy (≥ 5.86) were more likely to suffer from SCD (P &lt; 0.001 and P = 0.03) and CVD (P &lt; 0.001 and P = 0.02) in the entire cohort and the subgroup with low late gadolinium enhancement (LGE) extent (&lt;10%), respectively. In multivariable Cox analysis, following adjustment for the European Society of Cardiology predictors and the presence or absence of high LGE extent (≥10%), LV mean entropy was an independent predictor of SCD (hazard ratio [HR] 1.04, 95% CI 1.0 - 1.08, P = 0.03) and CVD (HR 1.06, 95% CI 1.04 - 1.09, P &lt; 0.001). An SCD and CVD predictive model that encompassed a combination of LV entropy and LGE was developed, and an internal validation showed that the derived models retained good predictive ability with a C-index of 0.71 to 0.74 and 0.81 ± 0.03 for SCD and CVD, respectively.

Conclusions
LV mean entropy derived from native T1 mapping, reflecting myocardial tissue heterogeneity, was an independent predictor of SCD and CVD in participants with HCM and could help improve risk stratification.Figure 1Kaplan-Meier Analyses.Figure 2Incremental Value of LV entropy