bluuebunny/crossref_metadata_2025 huggingface dataset:
The spectrum of ECG abnormalities in a large cohort of histologically proven cardiac tumors
Authors: Bavuso L L , Suma N , Marinelli V , Ciarlantini M , Casuso Alvarez M , Bela' R , Impellizzeri A , Bertolini D , Di Iuorio O , Pastore G , Ryabenko K , Foa' A , Rinaldi A , Armillotta M , Pizzi C
Published: October 2024

Background

Cardiac tumors represent a heterogeneous clinical scenario. The role of ECG in the diagnostic work-up remains to be investigated.

Objectives

To describe the spectrum of electrocardiographic abnormalities in a large cohort of histologically proven cardiac tumors and to evaluate potential red flags of malignancy.

Material and Methods

247 consecutive patients with histologically proven cardiac tumors and available ECG at Bologna University Hospital were enrolled. All ECGs were independently analyzed off-line using a manual caliper by two experienced cardiologists who were blinded to clinical information and histological results. In case of disagreements, a third consensus re-assessment was performed to resolve any discrepancies. Multivariable regression analysis was used to assess potential predictors of malignancy among electrocardiographic abnormalities.

Results

Of 247 patients, 98 (39.7%) had malignant tumors. Compared with patients with benign tumors, those with malignant tumors exhibited a higher heart rate, right axis deviation, greater depolarization, repolarization abnormalities and bradyarrhythmia at presentation. Regarding specific ECG features, a higher heart rate on admission (p=0.001), bradyarrhythmias (p=0.01), ischemic-like repolarization abnormalities (ST-segment deviation, both depression and elevation, and negative T-wave; p<0.001) and low voltages (p=0.005) were identified as independent predictors of malignancy.

Conclusion

ECG is frequently abnormal in case of malignant cardiac tumors. Some specific electrocardiographic changes could have a supportive role in the diagnostic workup of patients with cardiac tumors by increasing the clinical suspicion of malignancy.ECG Tumors
Early detection of liver fibrosis in patients with Fontan circulation using multiparametric magnetic resonance imaging
Authors: Klauco F , Valkovicova V , Bobocka K , Kaldararova M , Jezberova M , Zigrai M , Simkova I
Published: October 2024

Introduction

Fontan procedure (FP), serving as the palliative intervention for complex congenital heart diseases characterized by single-ventricle physiology, precipitates a spectrum of late-stage complications. Fontan-associated liver disease (FALD) encompassing liver fibrosis (LF) which may progress to liver cirrhosis (LC) and thereby hepatocellular carcinoma (HCC) is among the most serious. Despite its importance, optimal surveillance of FALD remains undefined. Multiparametric Liver Multiscan (LMS) with corrected T1 (cT1) value emerges as a novel magnetic resonance (MRI) based non-invasive quantitative tool for liver inflammation and fibrosis evaluation. Aim of this study was to ascertain prevalence and severity of LF utilizing LMS, alongside identifying contributory risk factors for LF in adults post-FP.

Material and methods

Our cohort included 29 adult patients after FP who underwent LMS. Median age was 25y (20-43y) 54% were females. Liver morphology was assessed by ultrasound (USG) and MRI-based LMS protocol. Hepatic scoring systems, including the Aspartate Aminotransferase to Platelet Ratio Index (APRI), Fibrosis-4 (FIB-4) Index, and Model for End-Stage Liver Disease (MELD), were computed. Additionally, presence of fenestrations in the Fontan circulation, hemoglobin levels (Hb), and blood oxygen saturation both at rest and during exercise (SatO2%) were evaluated.

Results

Median cT1 was 914 (±207) ms, in 87% exceeding normal threshold . In those with elevated cT1, LF was undetected by USG in 38%. LC was identified in 27% of the cohort by USG. LC group exhibited significantly higher cT1 values (P<0.001) compared to non-LC group. cT1 value >933ms was associated with a sensitivity of 89% and a specificity of 80% for diagnosing LC (AUC 0.92). Significant correlation was found between cT1 values and Hb (P=0.01) and desaturation (SatO2 <90%/ interventional closure of fenestration, P=0.004). Conventional liver tests and hepatic scoring systems (APRI/FIB-4/MELD) did not predict cT1 nor LC.

Conclusion

Our study confirmed that LF is almost widely prevalentamong adult patients with single-chamber circulation. Risk factors for LF are systemic desaturation (SatO2 <90% or interventional closure of fenestration) and polyglobulia. However, reliable FALD surveillance remains challenging. Conventional liver assessments and scoring algorithms fall short in delineating the full scope of LF or LC. Consequently, the integration of non-invasive LMS into routine follow-up regimens is advocated, given its pronounced sensitivity for detecting subclinical FALD manifestations and predicting LC. The LMS-derived cT1 value >933ms is a critical predictor for LC, underscoring its importance in guiding further patient monitoring, treatment, and facilitating early HCC detection.
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

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

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 > 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 > -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 > -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

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

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

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

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<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

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

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

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<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
Echocaridographic assessment of pulmonary hypertension: improving the probability
Authors: Wild C , Gurung A , Willis J , Slegg O , Rossdale J , Suntharalingham J , Mackenzie Ross R , Page J , Charalampopoulous T , Johnson M , Oxborough D , Thompson D , Peacock O , Coghlan G , Augustine D X
Published: October 2024

Introduction

Pulmonary hypertension (PH) is a cardio-pulmonary disorder characterised by raised pulmonary artery pressure (mPAP >20mmHg) leading to right ventricular failure, and death if left untreated. Transthoracic echocardiography (TTE) assessment of PH uses a probability-based approach, combining peak tricuspid regurgitant velocity with other supporting signs. We evaluated the latest ESC TTE PH guidelines in a real-world UK dataset and identified markers that may improve the sensitivity of the existing algorithm.

Method

Retrospective analysis of 447 patients referred for initial PH assessment. This was a select population of patients who underwent both TTE and right heart catheter (RHC) (mean time to RHC = 40±30 days). In addition to current TTE PH probability markers we analysed right ventricular free wall strain (RVFWS). Measurements were made by a single operator using Tomtec Arena 2020. Crosstabulation, ROC curve analysis and T-tests were used to compare variables between PH and no PH.

Results

Mean sample age was 64±15 yrs (61% female). 6.9% (n=4) of the no PH group had pulmonary mid-systolic notching, which may be due to pseudo-notching attributable to incomplete Doppler envelope. Sensitivity and specificity of current ESC TTE probability guidelines were 83%, and 65% respectively (95% C.I.). However, within the low probability group (i.e. those felt to be less likely to have PH) 62% (n=63) had confirmed PH at RHC (mPAP = 28±9). The addition of RVFWS as an additional marker to the existing supporting signs of PH (Table 1) resulted in an improvement of the sensitivity of the algorithm to 92% with a mild reduction in specificity (63%). The number of false negatives were reduced by 51%. Of these, the majority were in the low TTE probability group (n = 32).

Conclusions

Using current PH TTE probability algorithms classifies a significant proportion of those with PH as having a low TTE PH probability. The addition of RVFWS improves the sensitivity of the existing algorithm to 92% and reduces false negatives by 51%.
Biological effects of radiation exposure in patients treated with X-ray guided endovascular aortic repair
Authors: Yeong T T , Abdelhalim M A , Moquet J , Barnard S , O'brien G , Smith A , Badie C , Patel A S , Ainsbury E , Terry S Y A , Modarai B
Published: October 2024

Background

X-ray guided cardiovascular interventions such as endovascular aortic repair (EVAR) expose patients and operators to significant amounts of repeated ionising radiation over a long period of time. The biological effect of such protracted radiation exposure is poorly understood. We have previously demonstrated a higher incidence of dicentric chromosome (DC) aberrations in high-volume endovascular interventionalists and differences in acute DNA damage in lymphocytes between individuals following in vitro irradiation. Studies suggested a higher incidence of cancer in patients who underwent EVAR compared with those who have had open aneurysm repair, but the evidence is inconclusive. Further work is required to evaluate the biological radiation risk of X-ray guided cardiovascular interventions.

Purposes

We aimed to examine radiation-induced genome instability from patients after complex EVAR. We also aimed to investigate the intrinsic response of each patient to radiation using biomarkers of acute DNA damage following in vitro irradiation of their blood and to correlate this response to the expression of radiation-responsive genes.

Methods

Lymphocytes were isolated from patients after complex (branched/fenestrated) EVAR and non-irradiated controls. DC, a type of chromosomal aberration caused by radiation exposure were enumerated. γ-H2AX, a marker of acute DNA damage/repair, was measured by immunofluorescence after in vitro irradiation at 0.2 Gy and 1 Gy, along with the expression of the radiation-responsive genes FDXR, CCNG1, P21 and PHPT1 using qPCR.

Results

17 patients (82% male, median age 73[59 – 85years]) and 16 controls (56% male, median age 68[53 – 83years]) were recruited. The mean incidence of DC was 3.782 (95% CI 3.13 - 4.43) and 0.898 (95% CI 0.48 -1.32) per 1000 cells for patients and controls, respectively (P<0.0001). Patients had higher background of γ-H2AX foci than unexposed controls, (0.7056, 95% CI 0.316 - 1.10) vs (0.241 95% CI 0.077 - 0.405) per cell, P<0.05. FDXR expression was most increased following irradiation (P<0.0001), reaching a mean 13.1-fold and 11.4-fold increase at 4-hour and 24-hour time-point, respectively, but this upregulation was not significantly different between the two groups.

Conclusion

We have shown an increased frequency of chromosomal aberrations in patients after complex EVAR, a biological finding that may support a propensity to developing malignancies. Patients also have higher basal DNA damage/repair (γ-H2AX) activity. Expression of ferredoxin reductase, FDXR gene could be a potential radio-responsive biomarker to provide personalised biological dosimetry information for clinical monitoring. Our study further underlines the long-term radiation risk of X-ray guided cardiovascular interventions and the potential of biological assays that may guide personalised care.
High ABCD2-score after transient ischemic attack is associated with a two-fold higher stroke-rate during long-term follow-up
Authors: Al-Chaer K , Alhakak A , Vinding N , Butt J H , Johnsen S P , Kruuse C R , Schou M , Torp-Pedersen C , Koeber L , Fosboel E
Published: October 2024

Background

The ABCD2-score is a validated risk score used to estimate the short-term risk of stroke after transient ischemic attack (TIA). However, "real-world" contemporary data on the long-term risk of stroke after TIA according to ABCD2-score are needed in order to guide preventive strategies.

Purpose

To determine the long-term risk of stroke after TIA according to modified ABCD2-score (high-risk (≥4 points) versus low-risk (<4 points)).

Methods

Patients aged ≥18 years with first-time TIA were included from the Danish Stroke Registry (2014-2020). The study population was stratified in high-risk (≥4 points) and low-risk (<4 points) ABCD2-score group. We utilized a modified ABCD2-score consisting of the following parameters: age ≥60 years, hypertension, clinical features, and diabetes. The 3-year risk of ischemic stroke and all-cause mortality was compared between the high-risk and low-risk group using the Aalen-Johansen and Kaplan-Meier estimator. A cox regression model was also conducted.

Results

In total, 21,433 patients with first-time TIA were included; 1,281 (6.0%) in the high-risk and 20,152 (94.0%) in the low-risk group. Patients in the high-risk group were older (77.5 years [interquartile range [IQR] 70.8-84.1] versus 70.3 years [IQR 60.1-78.2]), more often females (52.2% versus 46.6%) (p <0.001), more comorbid and received more medication compared with the low-risk group at baseline. The 3-year cumulative incidence of stroke was 6.0% [95% CI: 4.6-7.5] in the high-risk group and 4.2% [95% CI: 3.9-4.5] in the low-risk group, and the unadjusted hazard ratio (HR) was 1.6 (95% CI 1.2 – 2.0) (Figure 1). The cumulative incidence of all-cause mortality within three-years after TIA was 28.9% [95% CI: 26.1-31.7] in the high-risk group and 10.3% [95% CI: 9.9-10.8] in the low-risk group. The unadjusted HR was 3.2 (95% CI 2.8 – 3.6).

Conclusions

Patients with high-risk ABCD2-scores had an almost two-fold higher associated long-term stroke-rate compared to those with low-risk scores. Trials focusing on preventive measures, including evidence-based antithrombotic strategies, especially for the high-risk group are warranted.
Machine learning identification of risk factors for ischaemic stroke in patients with heart failure with reduced ejection fraction but without atrial fibrillation: A report from WARCEF trial
Authors: Ishiguchi H , Chen Y , Huang B , Gue Y , Correa E , Homma S , Thompson J L P , Lip G Y H , Abdul-Rahim A H
Published: October 2024

Background

The prediction of ischaemic stroke in patients with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation (AF) remains challenging and risk stratification based clinical factors alone has limited discrimination. Our aim was to evaluate the performance of machine learning (ML) to identify risk factors for ischaemic stroke in such HFrEF patients.

Methods

We performed a post-hoc analysis of the WARCEF trial, only including patients without prior history of AF, and censoring those who developed incident AF during follow-up. We evaluated the performance of 9 ML models to identify risk factors for incident stroke, using metrics including area under the curve (AUC), precision, specificity, and decision curve analysis. The importance of each feature in constructing the model was quantified using SHapley Additive exPlanations (SHAP) values.

Results

We included 2,213 patients with HFrEF but without AF (mean age 59±12 years; 79% male). Of these, 74 (3.3%) had an ischaemic stroke during mean follow-up of 3.5±1.8 years. Out of the 29 patient-demographics variables, 12 were selected for the ML training.

All ML models demonstrated high AUC values, outperforming the CHA2DS2-VASc score (Figure 1). The logistic regression model exhibited a slight deviation from this trend. The XGBoost model achieved an AUC of 0.86 (95% confidence interval [CI]: 0.72-0.99), while the Random Forest model showed an AUC of 0.85 (95% CI: 0.74-0.96). Similarly, the Support Vector Machine and Light Gradient Boosting Machine models recorded AUCs of 0.85 (95% CI: 0.72-0.97) and 0.83 (95% CI: 0.70-0.96), respectively. Each of these models attained precision and specificity scores of 1.0, indicating high performance. These models consistently provided significant net clinical benefits. Key risk factors for stroke identified across these models were creatinine clearance and blood urea nitrogen. The use of warfarin appears to be protective.

Conclusions

Machine-learning models can identify risk factors for ischaemic stroke in patients with HFrEF but without AF. Worsening renal failure was predictive of an incident stroke, while warfarin use was protective against stroke (Figure 2).Figure 1Figure 2
Efficacy and safety of P2Y12 inhibitors plus aspirin versus aspirin alone in ischemic stroke or high-risk transient ischemic attack: a meta-analysis of randomized controlled trials
Authors: Ahmed M , Ahsan A , Fatima L , Basit J , Nashwan A J , Ali S , Hamza M , Karalis I , Ahmed R , Ijioma N N , Alraies M C
Published: October 2024

Background

Patients with mild ischemic stroke or transient ischemic attack (TIA) have an increased risk of recurrent stroke within 90 days after the onset of the initial thrombotic event. Antiplatelet therapy plays an essential role in reducing the risk of stroke recurrence. However, data regarding the efficacy and safety of dual antiplatelet therapy (DAPT) with P2Y12 inhibitors (clopidogrel/ticagrelor) and aspirin versus aspirin monotherapy is limited.

Purpose

We performed an updated systematic review and meta-analysis to evaluate the effectiveness of DAPT versus aspirin monotherapy in patients with mild ischemic stroke or TIA in the light of new published evidence. Moreover, we investigated whether antiplatelet therapy started within 72 hours is effective in reducing recurrent stroke as compared to the conventionally used 24-hour time window for initiating DAPT.

Methods

PubMed/MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) that compared DAPT with aspirin plus clopidogrel to aspirin alone started within 24 hours or 72 hours in patients with acute mild ischemic stroke or high-risk TIA from inception to December 31st, 2023. A random-effects model was used to pool risk ratios (RRs) and 95% confidence intervals (CIs) for clinical endpoints.

Results

Five RCTs with 27,563 patients were included in this study. DAPT significantly reduced the risk of recurrent stroke by 23% (RR: 0.77; 95% CI: 0.70-0.83; p<0.00001), ischemic stroke by 26% (RR: 0.74; 95% CI: 0.68-0.81; p<0.00001), and major adverse cardiovascular events (MACE) by 23% (RR: 0.77; 95% CI: 0.71-0.84; p<0.00001). However, DAPT was associated with a significantly increased risk of moderate or severe bleeding (RR: 2.19; 95% CI: 1.38-3.48; p=0.0009) and hemorrhagic stroke (RR: 2.08; 95% CI: 1.13-3.82; p=0.02). No significant differences were observed for all-cause death (RR: 1.28; 95% CI: 0.95-1.71; p=0.10), cardiovascular death (RR: 1.38; 95% CI: 0.81-2.33; p=0.23), and myocardial infarction (RR: 1.63; 95% CI: 0.77-3.46; p=0.20). We performed sensitivity analysis based on the hazard ratio reported by RCTs which showed comparable results. Subgroup analysis based on treatment onset time (therapy initiation within 24 hours of thrombotic event vs therapy initiation within 72 hours of thrombotic event) showed that both strategies were effective in reducing the risk of recurrent stroke. Subgroup analysis based on the duration of DAPT (21 days vs. 90 days) showed that DAPT for 90 days was associated with an increased risk of moderate or severe bleeding as compared to therapy lasting for 21 days.

Conclusion

DAPT with P2Y12 inhibitors and aspirin reduces the risk of recurrent stroke and MACE but is associated with an increased risk of moderate or severe bleeding.
Investigation of age-related in-hospital outcomes of left atrial appendage occlusion in germany
Authors: Voran J , Seoudy H , Leye M , Kreidel F , Frank D
Published: October 2024

Background

The aim of this study was to assess demographics, in-hospital mortality and baseline characteristics of hospital cases with a left atrial appendage occlusion (LAAO) procedure in relation to patient age.

Methods

This is a retrospective observational analysis of all German in-hospital cases from 2016 to 2022 with a coded LAAO procedure using the Diagnose Related Groups (DRG) statistics database of the Research Data Center of the Federal Statistical Office.

Results

In total 40435 cases were observed in the investigated time period. Over the 5 years studied we found a significant shift towards an older patient collective. Compared to 28,3% in 2016, in 2022 40,1% of all patients were over 80 years of age (a rise of 152 %). Cases of patients with over 85 years of age increased from 7.7 % to 11.4 % during the same time period. We observed an in-hospital death rate for patients <70, 70-75, 80-85 and >85 years of age in 0.8, 1.0, 1.4 and 2.2 % respectively. Further we saw significant higher rates of intensified care treatment, pericardial effusion, acute kidney injury and red blood cell transfusion for patients >80 years of age. In unadjusted and adjusted logistic regression models age was significantly associated with a higher rate of in-hospital death.

Conclusions

In this study we present real world data from a health-care-system level. Our main findings were an increasing age in patients undergoing LAAO procedures and an independent association of age with in-house mortality and complications. This data provides a further basis to balance risks and benefits of LAAO procedure as a preventive treatment.
Pulmonary artery pulsatility index evaluation in intermediate-to-high and high-risk pulmonary embolism patients underwent transcatheter intervention
Authors: Iannaccone M , Gamardella M , Fumarola F , Mangione R , Botti G , Russo F , Boccuzzi G
Published: October 2024

Background

The clinical impact of pulmonary embolism (PE) transcatheter intervention on the right ventricular function and its potential role as procedural outcomes has to be defined.

Methods

Consecutive patients who underwent pulmonary transcatheter intervention between 2021 and 2023 were included in an observational fashion. Data about clinical characteristics, PE risk stratification, pre and post-interventional pulmonary artery pressure (PAP) and Pulmonary Artery Pulsatility Index (PAPi) were collected. The primary endpoint was a composite of in-hospital death or repeated intervention.

Results

49 patients were included, mostly female gender (61.2%), with a mean age of 67±12,9 years old, 79.6% with > 1 PE risk factor, and 55% of them stratified as high-risk (HR) PE. 34.6% of the patients were treated with transcatheter thrombolysis (all in the intermediate-to-high-risk cohort), 20% with FlowTriever device, 53.4% with Indigo Cath8 or Lightning 12 device, 8.1% of the procedure was performed under ECMO support. All patients classified in intermediate-to-high risk (IHR) survived, and the mean PAP was reduced (33.4±10.9 to 24.3±7.1 mmHg p<0.01), as well as PAPi (2,3±0.35 to 1.68±0.26 p<0.01). 22% of the patients In IHR experienced the primary endpoint, in these populations, the mean PAP (pre 33±4.1 vs post 30.5±4.6 p=0.58) and PAPi (pre 1.35±.0.6 vs post 1.4±0.6 p=0.39) did not change significantly. On the other side, those who survived without events had a slight significative reduction in mean PAP (pre 32±6.7 vs post 24.6±4.3 p<0.02) while the PAPi significantly increased (1.2±0.6 vs 1.8±0.2 p<0.01). In the HR population, a delta PAPi > 0.45 demonstrated a 65.7% sensitivity and 75% Specificity for the primary outcome AUC 0.83 at ROC curve analysis.

Conclusion

Pulmonary Thrombus aspiration significantly changes the PAP and PAPi in patients with acute PE. While in IHR patients the overperforming PAPi seems to normalize, in HR patients it increases and may be a marker of procedural success and right ventricle recovery.