bluuebunny/crossref_metadata_2025_split huggingface dataset:
A meta-analysis of the effects of sacubitril-valsartan on surrogate markers of systemic right ventricular dysfunction in congenital heart disease
Authors: Braganca B , Pinho A I , Azevedo J , Andrade A , Rodrigues R A , Cruz C 
Published: October 2024

Abstract

Introduction
Dysfunction of systemic right ventricle (sRV) in adult congenital heart disease (ACHD) patients is expectable and often associated with heart failure and other dismal cardiovascular events. Despite limited evidence, several neurohormonal modulators approved for heart failure with reduced ejection fraction (HFrEF) have been used off-label in patients with RV dysfunction1. Sacubitril-valsartan (ARNI) effects on sRV remains poorly studied, with current evidence being limited to small cohorts.

Purpose
Review and summarize current evidence about the effects of ARNI in ACHD patients with sRV.

Methods
We performed a systematic review on MEDLINE, EMBASE, COCHRANE, and SCOPUS for articles that included "systemic right ventricle" and "sacubitril valsartan" until January 2024. Two investigators screened the literature and extracted data. Treatment effects were measured by Cohen's d effect-size (EZ) pre and post-ARNI, with a 95% confidence interval (CI), using a restricted maximum likelihood model.

Results
From 197 publications screened, five studies fulfilled our criteria, comprising a total of 135 patients. Follow-up after ARNI therapy ranged from 12 to 27 months. No randomized clinical trials were found, and only two studies had a prospective design. Dextro-transposition of the great arteries (D-TGA) after atrial switch operation was the most common type of congenital heart disease with sRV (n=95; 70%). Meta-analysis demonstrates that ARNI reduced NT-proBNP levels during follow-up (EZ= -0.34, CI -0.59 to 0.08; p=0.01; I2=4.0%). Regarding RV function, ARNI improved RV fractional area change (RVFAC) (EZ= 0.75, CI 0.01 to 1.50; p= 0.048; I2=85.0%). A trend for RV global longitudinal strain improvement was also observed with ARNI (EZ= 1.74, CI -0.05 to 3.54; p=0.06; I2=95.9%) but not for tricuspid annular plane systolic excursion (EZ= -0.07, CI -0.33 to 0.20; p=0.62; I2=0.0%). RV diastolic diameter did not change significantly with ARNI (EZ= 0.07, CI -0.43 to 0.56; p=0.79; I2=68.2%). A trend for improvement on the 6-minute walk test was observed (EZ= 1.89, CI -0.13 to 3.91; p=0.07; I2=96.3%), but no effect on exercise oxygen consumption (VO2) (EZ= -0.09, CI -1.32 to 1.15; p=0.89; I2=91.4%). During follow-up ARNI did not change significantly systolic blood pressure (EZ= -0.32, CI -0.74 to 0.11; p=0.15; I2=58.4%) or serum creatinine (EZ= 0.23, CI -0.04 to 0.49; p=0.09; I2=0.0%).

Conclusions
Despite heterogeneity among these studies, this meta-analysis demonstrates that ARNI might improve NT-proBNP levels and RV function. ARNI seems safe and well tolerated, with no significant effect on blood pressure and renal function. More well-powered studies are needed to confirm the beneficial effects of ARNI in ACHD with sRV.
Right ventricular global longitudinal strain by cardiac magnetic resonance feature tracking is associated with outcome in patients with a systemic right ventricle
Authors: Wustmann K , Valsangiacomo Buechel E , Ruperti-Repilado J , Greutmann M , Schwerzmann M , Bouchardy J , Rutz T , Tobler D , Gabriel H , Stambach D , Schwitter J , Burkhardt B 
Published: October 2024

Abstract

Introduction
It is well known, that patients with a systemic (sub-aortic) right ventricle (sRV) for congenitally-corrected transposition of the great arteries (TGA) or with complete TGA after atrial switch operation are more threatened to develop RV dysfunction, relevant supra- and ventricular tachycardia and have a reduced life expectancy. While the randomized, placebo-controlled, double-blinded, multi-centre SERVE trial to investigate the effect of phosphodiesterase-5 inhibitor tadalafil in sRV patients showed negative results on the primary end-point RV endsystolic volume (RVESV), aim of this sub-analysis was to evaluate RV global longitudinal strain (GLS), a more sensitive measure of RV function, by cardiac magnetic resonance (CMR) feature tracking (FT) over time, for treatment effect and to investigate whether RV GLS predicts clinical outcome in sRV patients.

Methods
CMR volumetric RV and FT parameters were analysed (blinded for patient and assessment time and treatment) at baseline and compared to follow-up (FU) after 3 years, or after 1 year in case of withdrawal of the study drug. FT was performed using appropriate software. Treatment effect was analysed using ANCOVA with baseline values and FU-time as covariates. Values of &gt; 4th quartile of RV GLS were used as cut-off for Kaplan-Meier analysis on the primary outcome, defined as a composite of all-cause death, clinically relevant arrhythmias and hospitalisation for heart failure.

Results
CMR exams were available for 78 patients at baseline (40±11 years, 33% females) and for 71 patients at FU. No treatment effect of tadalafil compared to the placebo was discovered for RV GLS (p=0.26), RVESVi (p=0.63) and RV ejection fraction (RVEF, p=0.6). Over a 3 years FU-time, RV GLS mildly increased (p=0.0023, figure 1). During FU, 14 patients experienced a clinical outcome: 1 death, 4 hospitalisations for heart failure, and 12 clinically relevant arrhythmic events. An RV GLS &gt; -13.4% was associated with adverse clinical outcome (p=0.003, figure 2).

Conclusion
In patients with a systemic RV, treatment with Tadalafil had no effect on CMR-derived RV global longitudinal strain compared to placebo. RV GLS changed significantly over the 3 years FU-time. A RV GLS value of &gt; -13.4% is associated with adverse clinical outcome in these patients.Figure 1Figure 2
4-year follow-up results of percutaneous closure of atrial septal defect with the total biodegradable poly-L-lactic acid device: date from a prospective, single-center trial
Authors: Li Y F , Xie Z F , Xie Y M , Wang S S , Zhang Z W 
Published: October 2024

Abstract

Background
The poly-L-lactic acid (PLLA) device is a novel, total biodegradable occluder dedicated to percutaneous closure of atrial septal defect (ASD) .Closure of ASD with the PLLA device has proven to be relatively safe and effective in our preclinical and first-in-human studies.

Objective
The aim of the study was to evaluate long-term safety and efficacy of the PLLA device in percutaneous closure of ASD in a large cohort of patients.

Methods
A prospective study enrolling patients who had a clinically significant ASD was conducted in our institution from May 2018 to August 2019. Percutaneous ASD closure was undertaken with the PLLA device. Evaluations were scheduled pre-hospital discharge and again at 1, 3, 6, 12, 24, 36 and 48 months post implantation. Primary endpoints were a composite of clinical success, including closure success and no major complications at the 48-month follow-up evaluation.

Results
A total of 52 patients (35 children, 55.8% females, median age 7.55 years, median weight 28.75Kg) underwent an attempt at percutaneous ASD closure with PLLA device. Successful device implantation was achieved in 50 (96.1%) of 52 patients with delivery attempts. All the 50 patients (100%) completed 4-year follow-up visit. Closure success at 4-year follow-up were 84% (42/50), with 8 patient (16%) reported to have clinically significant leaks, including 2 large residual leaks, 5 moderate residual leaks, and 1 small residual leak. 10 complications occurred, with 1 event of cardiac arrhythmia during procedure, and 9 follow-up events, consisting in cardiac arrhythmias (n=6), moderate or large mitral regurgitation (n=2), and headache (n=1).

Conclusion
Percutaneous ASD closure with PLLA device in human seems to be safe. However, increased occurrence of residual leaks overtime indicated that long-term efficacy of PLLA device in human was sub-optimal.TTE follow-up of a case with PLLA device
Reverse cardiac remodeling induced by endovascular treatment of coarctation of the aorta
Authors: Farrashi M , Habibi Khorasani S , Pouraliakbar H R , Mohebbi B , Moosavi J , Iranian M R , Forouzannia S M , Babaei M R , Afrooghe A , Firouzi A , Khajali Z , Saedi S , Sadeghipour P 
Published: October 2024

Abstract

Background
Previously, we have showed the 3-year clinical safety and efficacy of balloon expandable versus self-expandable stents in native coarctation of the aorta (CoA) in a randomized clinical trial (RCT). Very few prospective studies have addressed the changes of echocardiographic parameters in mid to long-term follow up of CoA patients treated endovascularly.

Purpose
We aimed to demonstrate the improvement of echocardiographic parameters among patients undergoing coarctoplasty with stent based on core laboratory-confirmed baseline and 3-year follow up transthoracic echocardiographic (TTE) images.

Methods
In the index RCT, adult patients with de novo native CoA were randomized into two groups based on stent types. All randomized patients received the 3-year structural follow-up including aortic CT angiography and TTE. The current prospective cohort substudy, included all patients with available baseline and three-year core laboratory TTEs.

Results
Of 92 patients initially randomized, 71 participated in the 3-year structural follow up. No baseline core lab images were available in 39 patients, and thus, 32 patients (a median age of 32 (24.8 – 37.5) years, (14 women [43.8%]) were included in this subgroup study. One out of the 32 patients presented with recoarctation which was successfully treated before the 3-year evaluation. Peak systolic gradient and end-systolic velocity of the coarctation stenting site were 17.38 ± 6.55 mmHg and 0.93 ± 0.24 m/s respectively in the 3-year follow-up. Septal E’ and lateral E’ velocities were improved significantly (8.6 ± 1.73 cm/s to 9.35 ± 2 cm/s, P = 0.02 and 12.74 ± 2.96 cm/s to 13.92 ± 2.44 cm/s, P = 0.03, respectively). In addition, septal E/E’ ratio (10.84 ± 2.83 to 9.21 ± 3.17, P = 0.02) and lateral E/E’ ratio (7.39 ± 2.24 to 6.29 ± 1.97, P = 0.02) showed significant improvement. Significant reduction in LV mass [160 (130–203) g to 142 (IQR= 121–172) g, P = 0.001], and septal and posterior LV thicknesses were also demonstrated (0.9 (0.8–1.0) cm to 0.81 (0.77–0.93) cm, P = 0.004) and 0.92 ± 0.14 cm to 0.85 ±0.09 cm, P = 0.01, respectively). Twelve (37.5%) patients had baseline LVH which was normalized in 9 (75%). Lastly, 12 (41.3%) of our population had diastolic dysfunction at baseline study which significantly decreased to 4 (13.7%) in the three-year follow-up evaluation.

Conclusion
In the present core laboratory-based study, coarctoplasty with stent has favorable effects on diastolic function and LV hypertrophy during midterm follow-up in adult population with de novo native aortic coarctation treated with stent.
CILP1 and NTproBNP in pulmonary hypertension and right ventricular pressure overload: a translational experimental study
Authors: Garcia Lunar I , Dantas A P , Ascaso M , Pruna R , Galan-Arriola C , Sandoval E , Solanes N , Rigol M , Ibanez B , Pereda D , Garcia-Alvarez A 
Published: October 2024

Abstract

Introduction
Cartilage intermediate layer protein 1 (CILP1) has emerged as a novel marker of right ventricular (RV) dysfunction in pulmonary hypertension (PH), although there is still little evidence on its role in different scenarios of RV pressure overload. The aim of our study was to analyze CILP1 as a biomarker of RV remodeling and PH severity, and compare it with N-terminal pro-brain natriuretic peptide (NTproBNP), in different experimental models of RV pressure overload.

Methods
Three different experimental models of RV pressure overload compared to a sham procedure were evaluated in 24 Yucatan pigs: chronic postcapillary PH by pulmonary vein banding (M1, n=6); chronic PH by aorto-pulmonary shunting (M2, n=6); RV pressure overload by PA banding (thus without PH) (M3, n=6); and sham procedure (M0, n=6). Animals were evaluated at 8 months after surgery by right heart catheterization, cardiac magnetic resonance (CMR), and blood/histological sampling. Levels of CILP1 and NTproBNP at the RV myocardium and blood were determined with dedicated ELISA and compared among groups by Wilcoxon test with Bonferroni correction. Associations between biomarkers and RV performance indices and pulmonary arterial pressure (PAP) were assessed with Spearman correlation test.

Results
M1 animals developed chronic postcapillary PH with normal left ventricular (LV) performance and RV maladaptive hypertrophy (RV fibrosis and systolic dysfunction). M2 animals developed chronic precapillary PH associated with LV dilatation and RV maladaptive hypertrophy. On contrast, M3-animals developed severe RV pressure overload (without PH) and hypertrophy but maintained normal RV systolic function. CILP1 and NTproBNP levels were moderately correlated (R=0.56, p=0.002). CILP1 levels in RV myocardium and plasma were significantly higher in M1, whereas NTproBNP plasma levels were significantly higher in M2 (Figure 1). CILP1 in plasma and RV myocardium significantly correlated with PAP, while myocardial CILP1 levels also correlated with RV extracellular volume (RV-ECV) by CMR (Figure 2). NTproBNP myocardial levels correlated with RV ejection fraction and RV-ECV and plasmatic levels correlated with PAP (Figure 2).

Conclusions
CILP1 levels were increased in the presence of PH and isolated RV dysfunction, whereas NTproBNP levels were increased in the model of PH, RV dysfunction and LV remodeling. Myocardial levels of both peptides correlated with diffuse fibrosis, estimated by CMR, whereas plasmatic levels of both biomarkers correlated with PAP. This suggests that CILP1 may be a more specific marker of RV dysfunction in PH, being less dependent of LV parameters.CILP1 and NTproBNP levels among modelsCorrelation with PAP & RV remodeling
The relationship of clinical presentation, d-dimer levels and previous SARS-CoV-2 positivity in outpatients with suspected pulmonary embolism
Authors: Stankovic I , Milovanovic N , Grujicic K , Vranic I , Janeski N , Neskovic A N 
Published: October 2024

Abstract

Introduction
Elevated D-dimer levels can be detected in patients with pulmonary embolism (PE), but also in patients with the disease caused by the novel coronavirus (COVID-19).

Aims
To investigate relationship between clinical presentation, D-dimer levels and previous SARS-CoV-2 positivity in outpatients with suspected PE.

Material and methods
This retrospective study included 609 consecutive outpatients (mean age 68±15 years, 50% female) who underwent computed tomography pulmonary angiography for suspected PE from 2021 to 2023. By reviewing electronic databases, clinical and laboratory data were collected, as well data on previously documented SARS-CoV-2 infection.

Results
PE was confirmed in 130 (21%) patients who had higher D-dimer values than patients without PE (p&lt;0.001). Patients with previous COVID-19 had significantly higher D-dimer values compared to those without prior COVID-19, but only during the first 8 months from infection to pulmonary angiography (Figure, upper panel). Clinical probability of PE, as indicated by Geneva score [odds ratio (OR) 2.36, 95% confidence interval (CI) 1.55 – 3.58)], and age-adjusted D-dimer (OR 4.52, 95%CI 1.58 – 12.90) were independently associated with PE, while previous COVID-19 was not. Main clinical reasons for emergency department presentation are shown in Figure (bottom panel). In 45/609 (7.4%) patients evaluated primarily for elevated D-dimer, the prevalence of COVID-19 in the previous 6 months was higher in those with PE compared to those without PE (100% vs. 49%, p=0.019).

Conclusion
Within 8 months of infection, patients with a history of COVID-19 had higher D-dimer levels than those without COVID-19. Age-adjusted D-dimer and standard clinical probability scores retained their predictive power in outpatients with suspected PE, regardless of COVID-19 history.
Incidence, patient characteristics, and treatment patterns of U.S. active-duty service members diagnosed with COVID-19-associated VTE in the outpatient setting
Authors: Pearman J , Kelly F , Kobakhidze G , Ganesh Z , Mcquistan A , Fentanes E 
Published: October 2024

Abstract

Background
Venous Thromboembolism (VTE) is a well-established complication of acute coronavirus disease 2019 (COVID-19) infection. We sought to clarify the incidence, patient characteristics, and treatment patterns of VTE within United States active-duty service members (ADSM) diagnosed with COVID-19 infection in the outpatient setting.

Methods
Our team conducted a multicenter retrospective review of the outpatient healthcare records for all U.S. ADSM diagnosed COVID-19-associated VTE between January 1, 2020, and April 30, 2022. The data was obtained from the COVID-19 surveillance case list maintained by the Armed Services Health Surveillance Division (ASHSD) of the U.S. Defense Health Agency (DHA). The Defense Medical Surveillance System (a database containing inpatient and outpatient electronic medical records for active-duty service members) was used to capture all appropriate medical encounters using ICD-10 coding for venous thromboembolic events within 365 days of COVID-19 diagnosis. Chart review for data adjudication was performed by the physician investigator team.

Results
Among 365,788 ADSM who were diagnosed with COVID-19 in the outpatient setting, a total of 159 patients were identified as having COVID-19-associated VTE. The overall incidence rate of VTE was 43.47 per 100,000 people within 365 days of diagnosis (90-day incidence rate of 32.5/100,000). The median time from COVID-19 diagnosis to VTE was 23 days (IQR 13-87). Of 159 patients, 33 (20.7%) were diagnosed with DVT, 143 (90%) with PE, and 20 (12.5%) with both PE and DVT. The median age was 30 years old (IQR 23-38). The majority of patients were male (85%). 49% were white. The most common medical comorbidity was obesity (33%), 11% had a history of active tobacco use, and 9.4% of patients had a prior VTE diagnosis. Only 34% of patients were vaccinated for COVID-19 prior to their diagnosis (35 Pfizer–BioNTech, 13 Moderna, and 4 other). 148 (93%) of patients were treated with a direct oral anticoagulant, 10 (6.2%) were treated with low molecular weight heparin, and 1 (0.8%) was treated with a vitamin K antagonist. 96 (60.3%) required hospitalization with 4 (2.5%) requiring subsequent thrombectomy. None experienced major bleeding events. Only 2 (1.3%) of the patients died within 22 days from VTE diagnosis. The remaining 98.7% were alive at 875 days (SD 230) of follow-up.

Conclusion
The incidence of venous thromboembolism in active-duty military patients with COVID-19 was rare, affecting mostly unvaccinated, minority men in their 30s with risk factors such as obesity, prior VTE, and prior tobacco use. Of the women with VTE, 54% were non-white minorities. While VTE diagnosis was associated with a low mortality rate, the majority of patients required hospitalization.
A novel dynamic risk score to predict Clinically Significant Bleeding (CSB) after 3 months of anticoagulation in patients with incident Venous ThromboEmbolism (VTE) and without active cancer
Authors: Cohen A , Choudhuri S , Khan I , Pollock K , Bober-Irizar M , Galias Z , Irizar A , Bober M 
Published: October 2024

Abstract

Background
Predicting the risk of clinically significant bleeding (CSB), bleeding requiring hospitalisation or fatal bleeding, during and following anticoagulation is complex. Current models lack the ability to adapt to changing patient conditions over time and fail to account for the direct impact of anticoagulation in real-world clinical settings.

Purpose
To develop a dynamic risk prediction model for CSB to help clinicians decide on the duration of anticoagulant therapy in conjunction with a model for recurrences of VTE (also submitted to the conference).

Methods
UK Clinical Practice Research Datalink data (2001-2020) was used to generate a retrospective cohort with first VTE who had received 3 months of anticoagulation. Patient episodes of CSB and recurrent VTE were evaluated. Covariates were collected at baseline and subsequently as time-varying data to capture changes post-VTE. Hazards with 95% confidence intervals (CI) were estimated and covariates included in a Fine & Gray model used as predictors of CSB. An additive (logarithmic) scoring scheme was developed from subdistribution hazard ratios, discrimination (expressed by the C-statistic) estimated from 10-fold cross-validation.

Results
51,621 patients with a first VTE were included; 3307 CSB were identified in 206,292 person-years of observation. Incidence rates for CSB were 1.60 per 100 person-years. 18 independent predictors of CSB (recorded before or after the VTE diagnosis) were included in the model, Table 1. Patients recognised as lower-risk, medium and higher-risk (67.5 %, 15.9 % and 16.7 % of the population, respectively, at 90 days after first VTE, assuming no anticoagulation treatment) had an annualised incidence rate of 0.84, 2.94, and 9.45 per 100 person-years. The C-statistic for CSB was 0.78 (95%CI, 0.77-0.79). The points scored can be added to predict risk (Table 2).

Conclusions
Our dynamic score effectively identifies patients at risk of CSB three months post their initial VTE diagnosis. It allows for continuous monitoring of risk, and modelling of treatment impact, providing clinicians with a pragmatic tool to help determine treatment duration, and adapt their strategies in response to evolving patient conditions.Table 1:Predictors for CSBTable 2:CSB risk score
May right heart failure cause pulmonary congestion in pulmonary arterial hypertension?
Authors: D'alto M , Di Maio M , Romeo E , Argiento P , Liccardo B , Del Giudice C , Renon F , Vergara A , Caiazza E , Del Vecchio G , Sarubbi B , Gargani L , Rea G , Picano E , Naeije R 
Published: October 2024

Abstract

Aims
Recent studies have shown that lung ultrasound-assessed pulmonary congestion is worse in heart failure when pulmonary vascular resistance (PVR) is increased, suggesting a paradoxical relationship between right heart failure and increased lung water content. Accordingly, we wondered if lung ultrasound would reveal otherwise clinically silent pulmonary congestion in patients with pulmonary arterial hypertension (PAH).

Methods and results
All patients referred for suspicion of PAH in a tertiary center from January 2020 to December 2022 underwent a complete diagnostic work-up including echocardiography, lung ultrasound and right heart catheterization. Pulmonary congestion was identified by lung ultrasound B-lines using an 8-site scan. The study enrolled 102 patients with idiopathic PAH (mean age 53±13; 71% female). WHO functional classes I, II and III were found respectively in 2, 52 and 46% of them. The N-terminal-pro-brain natriuretic peptide (NT-proBNP) was 377 pg/mL [interquartile range, IQR 218, 906]. B-lines were identified in 77 out of 102 patients (75%), with a median of 3 [IQR: 1-5]. At univariable analysis B-lines were positively correlated to male sex, age, NT-proBNP, systolic PA pressure (sPAP), right atrial pressure (RAP), PVR, left ventricular end-diastolic volume and tricuspid annulus plane systolic excursion (TAPSE), and negatively to cardiac output and stroke volume. At multivariable analysis, RAP (p&lt;0.001; Fig 1), TAPSE/sPAP (p=0.001), and NT-proBNP (p=0.04) were independent predictors of B-lines.

Conclusion
Lung ultrasound commonly discloses pulmonary congestion in PAH. This finding is related to right ventricle to pulmonary artery uncoupling, and may tentatively be explained by increased central venous pressure impeding lymphatic outflow.Figure 1