bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with non-publication of clinical trials in cardiovascular medicine: a cross-sectional analysis
Authors: Alawajneh M , Aljabai A , Theeb L , Badwan Z , Abd Alnabi A , Theeb H , Altibi A 
Published: October 2024

Abstract

Background/introduction
Cardiovascular medicine is the fourth most-funded area of clinical research as it received an estimate for 7% of the total research funding. Nearly 8% of all clinical trials are cardiovascular-related (1,2). Non-publication of the registered clinical trials wastes money and time, encourages dissemination bias, and creates a body of possibly inaccurate literature, all of which obstruct scientific advancement. (3)

Purpose
To study the factors associated with the non-publication of cardiovascular clinical trials between January 2000 and June 2022.

Methods
We performed a cross-sectional analysis using ClinicalTrials.gov to determine all completed, discontinued, published, and unpublished cardiovascular medicine clinical trials between January 2000 and June 2022. For each trial, data on the trial phase, funding source, intervention type, enrolment size, trial completion, and publication status were extracted and subjected to logistic regression to determine clinical trial publication predictor factors.

Results
Among 3946 trials in cardiovascular medicine registered in ClinicalTrials.gov, there were 3215 completed trials included in the analysis. Of these, 34.2% (n=1100) were unpublished. On multivariate logistic regression, triple-blinded and quadruple-blinded trials were less likely to be unpublished compared to open-label trials (odds ratio [OR] 0.622; 95% confidence interval [CI] 0.45-0.85; p=0.003) and (OR 0.54; CI 0.42-0.69; p&lt;0.001), respectively. Enrolment of 100 participants or more was associated with a decreased likelihood of non-publication (OR 0.46; CI 0.39-0.55; p&lt;0.001). In addition, randomised trials were less likely to be unpublished than non-randomised trials (OR 0.67; CI 0.50-0.88; p=0.004). There was no significant effect of the intervention type, phase of the trial, trial participants' age and gender, or the trial funding resource on the publication status of cardiovascular medicine clinical trials.

Conclusions
It is observed that a considerable number of clinical trials in cardiovascular medicine remain unpublished. This issue raises some concerns regarding the risks and discomfort participants may encounter during the trial, while no results are added to the literature. Blinding of the trials, enrolment size, and allocation methods are the main predictors of trial publication.Forest plot of logistic regression
Efficacy and safety of catheter ablation for idiopathic premature ventricular contraction in Japan: from the nationwide Japan Catheter Ablation Registry
Authors: Goto K , Miyazaki S , Tonegawa-Kuji R , Kanaoka K , Yamashita S , Sasano T , Iwanaga Y , Nakai M , Inoue K , Kusano K , Yamane T , Shimizu W 
Published: October 2024

Abstract

Introduction
Catheter ablation (CA) is a viable approach for managing frequent idiopathic premature ventricular contractions (PVCs) associated with PVC-related cardiomyopathy. However, the real-world outcomes and appropriate indications for CA need further clarification.

Methods
This is the first nationwide analysis focusing on the efficacy and safety of CA of idiopathic PVCs. We analyzed 6,751 patients (age 58 [45-70], 3,265 males [48.4%]) who underwent their first CA for idiopathic PVCs with a single origin (3,849 right ventricular [RV] outflow tract [OT], 614 other RV, 1,517 in left ventricular [LV]-OT, and 771 in other LV), based on the Japanese Catheter Ablation Registry between August 2017 and December 2020.

Results
Success at discharge (SAD) was achieved in 5,276 (78.1%) patients, while 238 patients experienced recurrence before discharge (4.3% of those with acute success). SAD was achieved in 3,236/3,849 (84.1%) RVOT, 379/614 (61.7%) other RV, 1,145/1,517 (75.5%) LVOT, and 516/771 (66.9%) other LV patients (P &lt;0.001). Age &lt;50 and females were independent predictors for SAD. Conversely, obesity, origins other than RVOT, and low-volume facilities were independently inversely related to SAD. 171 (2.5%) acute complications, including 125 cardiac tamponades (CTs) (1.9%), were reported. Age ≥60 and females were independent predictors for both total complications and CTs. Remarkably, females aged ≥80 with RVOT origins exhibited a 10.3% rate of CTs.

Conclusion
Female patients aged &lt;50 with OT-PVC without obesity, demonstrated favorable efficacy. However, non-OT PVCs were independently inversely related to SAD. Special attention should be given to females aged ≥60 with RVOT origins.
VSIG4 inhibits the anti-inflammatory reaction of immune cells after cardiogenic shock
Authors: Erbe S , Kneuer J , Buettner P , Thiele H , Laufs U , Boeckel J N 
Published: October 2024

Abstract
Cardiogenic shock (CS) still has a mortality rate of approximately 50%. CS leads to a significant activation of the immune system. The aim of this study was to characterize the immune cell populations and the immune cell-specific changes in CS on admission to the clinic and after revascularization. We developed a web-based platform named 'IRCaS - Immune Cell Regulations in Cardiogenic Shock' to map the temporal course of immune cell-specific processes of CS after acute myocardial infarction (AMI) from admission to 3 days after revascularization. Our tool revealed an endogenous anti-inflammatory response after CS, which is inhibited by the cell-cell receptor VSIG4.
The web platform contains newly acquired single-cell sequencing data from patients with CS after AMI on admission and 24, 48, and 72 hours after revascularisation, as well as controls. In total, 171,962 immune cells derived from peripheral blood mononuclear cells (PBMCs) were individually sequenced. Analysis of the immune cell populations revealed, that 24 hours after revascularisation, monocytes increased to 62.4% (vs. 30.4% in controls), while T cells decreased from 46.3% to 25.0%. On the immune cell expression level, we observed an inflammatory response indicated by IL1B which continuously increased from 24 h (1.6+fold), over 48h (3.1+fold) to 72 h (3.5+fold) after revascularization. Interestingly, there was a significant anti-inflammatory response shortly after revascularization, as evidenced by a transient increase in the anti-inflammatory CD16+ monocyte subpopulation from 12.1% to 26.7% at 24 hours and an increase in THBS1 after revascularization, which was only short-lived. We identified a negative feedback in the increasing anti-inflammatory CD16+ cells caused by a subsequent VSIG4 (+5.2-fold) increase. Indeed, overexpression of VSIG4 in monocytes resulted in a significant decrease of anti-inflammatory CD16+ monocytes by 33.9% and a decrease in anti-inflammatory transcripts.
Our data show that in addition to the strong inflammatory response in CS, there is also an opposing anti-inflammatory response, which is however only short-lived, as it is attenuated by a negative feedback via an increase in VSIG4. In addition, our webplatform offers time-dynamic gene expression profiles of immune cells, allowing users to select and visualize specific genes during the course of CS after AMI.
Dysfunctional atrial fibroblast processing of filamin A in atrial fibrillation
Authors: Johnston A M , Yiu C H K , Moreira L A , Srivastava V , Sayeed R , Walcot N R H , Sastry P , Smart N , Reilly S 
Published: October 2024

Abstract

Background/Introduction
Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is associated with atrial structural remodelling, hallmarked by fibrosis. Atrial fibrosis is instigated by atrial fibroblasts (AFBs). It was previously uncovered the hormone calcitonin (CT) is produced in the heart and, via binding to the CT-receptors (CTR), inhibits atrial fibrogenesis and fibroblast profibrotic activity. [1] In AF, abnormally increased CTR internalisation causes loss of physiological surface CTR and prevents fibroblast activation by CT. The molecular mechanisms of this phenomenon in ACFs are unknown.

Aim
To explore the role of filamin A (FLNa), an actin cross-linking protein that was previously shown to interact with CTR, [2] in the regulation of CTR trafficking.

Methods
AFBs were enzymatically isolated from left atrial appendage biopsies collected from 30 patients in persistent AF or normal sinus rhythm (SR, controls) undergoing elective heart surgery. Immunostaining assessed the localisation of CTR and its overlap with the nucleus (stained with DAPI) and FLNa in AFBs. Co-localisation was quantified by the JACoP BIOP plugin for ImageJ. Target mRNA expression was assessed by RT-qPCR and protein levels by immunoblot. Immunoprecipitation (IP) then immunoblot (IB) validated protein-protein interactions. Calpain activity was assessed with a fluorescence-based assay. The effects of calpains on FLNa proteolytic processing was examined with calpain inhibitor calpeptin (10nM–100nM vs DMSO loading control).

Results
Immunostaining revealed aberrant, intracellular localisation of CTR in AF-AFBs (A) with increased nuclear localisation (p=0.03) and reduced co-localisation with FLNa (p=0.03). FLNa gene expression showed a trend towards reduction in AF (by 36%, p=0.06; B). Meanwhile, although full-length FLNa protein was unaltered in AF, there was a striking 67% reduction (p=0.02) in the expression of FLNa’s c-terminal fragment (FLNaCT), which contains the CTR binding domain (C). Co-immunoprecipitation confirmed a physical interaction between CTR and FLNaCT (D) in both SR and AF AFBs. FLNaCT is typically generated when FLNa is cleaved by the protease calpain 1, whose protein (F) but not mRNA (E), was significantly downregulated (71%, p&lt;0.001) in AF. Puzzlingly, a ~70% loss of calpain 1 protein was associated with unchanged calpain activity (G) and FLNaCT levels in AFBs treated with calpain inhibitor calpeptin (H).

Conclusions
Persistent AF is associated with an aberrant CTR localisation and FLNa proteolytic processing, not attributable to altered calpain activity. Further characterisation of the molecular determinants of the altered CTR localisation may uncover novel and potentially druggable facets of structural remodelling in AF.
Resolution of silent left atrial thrombi and clinical outcomes in patients with atrial fibrillation: insight from the LAT trial
Authors: Koichi I , Okada M , Tanaka N , Mishima T , Ozaki T , Osaki S , Masuda M , Sunaga A , Sotomi Y , Hikoso S , Nakatani D , Sakata Y 
Published: October 2024

Abstract

Background
Silent thrombi in the left atrium (LA), which are thrombi that have not yet caused thromboembolism, are occasionally observed in patients undergoing transesophageal echocardiography (TEE) for atrial fibrillation (AF). However, there is limited data regarding the impact of resolving these silent LA thrombi (LAT) on patient outcomes.

Methods
We conducted a retrospective review of clinical records from 2010 to 2018 at six hospitals, involving 17,436 TEE procedures for patients with AF. Among these, 297 patients (1.7%) were identified with silent LAT. Of these, 169 patients with follow-up TEE or cardiac computed tomography data for assessing the resolution of LAT were included in this study. The study population were categorized into two groups: the successful resolution group, defined as those with complete LAT resolution without any related events (N=130), and the failed resolution group (N=39). The latter included patients with residual LAT at the last follow-up (N=26), individuals with thromboembolic events (N=8), or those who required surgical intervention for LAT (N=5).

Results
During the median follow-up period of 394 days (interquartile range, 373-421 days) following thrombi detection, ischemic stroke and systemic thromboembolism (IS/SE) were observed in 10 cases, major bleeding in 23 cases, and all-cause death in 8 cases. In comparison to the successful resolution group, the failed resolution group not only exhibited a higher incidence of IS/SE (1.5% in the successful vs. 20.5% in the failed resolution group, Log-rank p &lt; 0.001) but also showed trends toward increased major bleeding (10% vs. 23.1%, p = 0.033) and higher total mortality rates (3.1% vs. 10.3%, p = 0.05). These differences in composite endpoints were also statistically significant (13.9% vs. 35.9%, p = 0.001).

Conclusion
In patients with silent LATs were identified, non-resolution of these LATs was associated with not only a higher incidence of IS/SE but also increased rates of major bleeding and all-cause mortality. Conversely, patients who experienced LAT resolution exhibited more preferable prognoses. The status of LAT resolution is closely associated with patient outcomes, underscoring the importance of monitoring LAT resolution in stratifying patient prognoses.
Maintenance of sinus rhythm is associated with lower incidence of stroke in patients with drug-refractory atrial fibrillation
Authors: Kim S , Choi Y , Park S , Kim S H , Oh Y S , Kim H 
Published: October 2024

Abstract

Introduction
Recent studies have demonstrated that early rhythm control for first-line treatment of atrial fibrillation (AF) improved cardiovascular outcomes. However, there is limited data regarding the long-term outcome of patients who failed antiarrhythmic drugs and who refuse radiofrequency catheter ablation (RFCA).

Methods
Patients with AF who were refractory to antiarrhythmic drugs and had refused further rhythm control attempts via RFCA were retrospectively identified and propensity-score matched with who had been treated with RFCA. The primary outcome of interest was all-cause mortality or ischemic stroke.

Results
A total of 169 patients who refused rhythm control with RFCA and propensity-score matched 169 patients who had been treated with RFCA were included for analysis. During a mean follow-up of 4.3[2.3;6.9] years, maintenance of sinus rhythm was more achieved in RFCA group (7 [4.1%] in Refuse group vs. 133 [78.7%] in RFCA group, p&lt;0.001). the incidence of ischemic stroke was significantly higher in patients who refused RFCA compared with patients who underwent RFCA (24 [14.2%] vs. 6 [3.5%], log-rank p&lt;0.001), but all-cause mortality was not significantly different (log-rank p=0.8). Refusal of attempted rhythm control via RFCA was an independent risk factor for ischemic stroke on multivariate Cox analysis (hazard ratio 3.2; 95% confidence interval 1.2 to 8.53, p=0.02). The risk of major adverse cardiovascular events (MACE) were also significantly higher in Refuse group (31 [18.3%] vs. 12 [7.1%], HR 3.83, 95% CI 1.57-9.37, p=0.003).

Conclusion
In patients with antiarrhythmic drug-refractory AF, maintenance of sinus rhythm was significantly different dependent on rhythm control via RFCA, therefore the risk of stroke was significantly higher in patients who refused rhythm control via RFCA compared with that of those treated with RFCA.
A mcgyvering way to left bundle branch area pacing : using the treadmill test machine ECG system and modified V1 / V6 leads connected to the pacing system analyser for left bundle branch area pacing
Authors: Pattu Valappil S , Pasupati U S , Krishnaswamy S , Jaiswal P K , Prasad G N , Jayanthi K , Srinath T S 
Published: October 2024

Abstract

Background
Left bundle branch area pacing (LBBaP) is a novel pacing modality which provides physiological synchronisation of both the ventricles. However, its use and adoption requires the presence of a standardised electrophysiological (EP) system with 12 lead ECG to show left bundle branch area capture.

Purpose
The aim of the study was to assess the feasibility and outcomes of using the conventional treadmill test (TMT) machine 12 lead ECG system and modified V1 and V6 leads connected to the pacing system analyser (PSA) to demonstrate conduction system capture during left bundle branch area pacing (LBBaP).

Methods
LBBaP was attempted by a single operator in a mixed cohort of patients at peripheral hospitals lacking the standardised EP system. The presence of LBB area capture was tested with the aid of the 12 lead ECG system connected to the standard TMT machine (1). Conduction system capture was also assessed using modified V1 and V6 leads connected to the PSA for measurement of V6 left ventricular activation time (LVAT)(2) . The baseline clinical, procedural, pacing, electrocardiographic parameters, echocardiographic response (&gt; 10% improvement in ejection fraction {EF}) and clinical response to LBBaP were assessed.

Results
LBBaP was attempted in 19 patients and was successful in 18 patients (94.7%). Patient characteristics include age 66.7 +/- 11.47 years, female 47.37%, male 52.63%, ischaemic cardiomyopathy 10.52% and non-ischaemic cardiomyopathy 5.26% .The mean baseline EF and QRS duration was 45%+/-14% and 130.18 +/-10.45 milliseconds(ms) respectively. LBBaP threshold was 0.59 +/-0.168 volts and R wave amplitude was 12+/-3.5 millimetres , which remained stable during the mean follow up of 15.9 +/-13.67 months. The mean fluoroscopic duration was 11.57 +/-2.58 minutes and procedural time was 108.78+/-29.20 minutes. LBBaP resulted in impressive narrowing of the QRS duration to 102.39 +/-10.55 ms (p&lt;0.001) with LVAT of 68.94 +/-9.94 ms. LVEF improved in the patients with cardiomyopathy from 33.4 +/- 5.77 % to 48.2+/-12.37 % (p=0.028) .Clinical and echocardiographic response was noted in 87.5% of patients with cardiomyopathy.

Conclusion
The 12 lead ECG system with the standardised TMT machine in conjunction with the modified V1 and V6 leads connected to the PSA is a feasible alternative to the EP system to perform successful left bundle branch area pacing.ECG leads connected during LBBapClinical profile of patients
Long-term efficacy of cardiac resynchronization therapy with triple-site ventricular stimulation in heart failure patients
Authors: Ogano M , Iwasaki Y , Kimura K , Kawanaka H , Tajiri M , Tanabe J , Shimizu W , Asai K 
Published: October 2024

Abstract

Background
Cardiac resynchronization therapy (CRT) reduces cardiac electrical dyssyncrhony and improves clinical outcomes in selected symptomatic patients with left ventricular (LV) systolic dysfunction. However, patients after conventional CRT (Bi-V) have residual cardiac electrical dyssynchrony. CRT with multi-site pacing has gained attention to improve short-term outcome refractory to BiV. However, long-term follow up outcome is still uncertain. We evaluated the efficacy of CRT with triple-site ventricular stimulation (Tri-V), involving 2 LV lead in 2 anatomically separated veins and a single RV lead in RV apex for long-term follow up period.

Methods
Ninety-two consecutive patients with New York Heart Association class II-IV heart failure, LV ejection fraction &lt;0.35, and QRS interval &gt;120ms, who underwent CRT implantation between 2010 and 2016, were enrolled. Acute hemodynamic responses to temporary dual-site and triple-site ventricular pacing were evaluated, and patients were assigned to either the Bi-V or Tri-V group based on the results. The primary endpoint was the HF clinical composite score, which scores patients as improved, unchanged, or worsened. The secondary endpoint included cumulative survival from any cause of death and HF hospitalization.

Results
Tri-V was successfully implanted in 32 patients. Five patients were excluded during follow-up because of uncaptured pacing in one of the LV leads. One year post-implantation, the clinical composite score significantly improved in 84% of Tri-V patients compared to 57% in the Bi-V group (p=0.026). After a median follow-up of 12.0 years, there was no significant difference about all-cause mortality between Tri-V and Bi-V (p=0.147). However, Tri-V group showed significant lower HF hospitalization (p=0.005) than Bi-V group. The number of battery exchange was not significantly different between Tri-V than Bi-V group (1.4±0.7 vs. 1.2±0.8, p=0.361).

Conclusion
CRT with Tri-V, characterized by stable lead parameters, appears to offer greater long-term benefits than Bi-V in terms of clinical status without excessive battery exchanges.figure
Estimated transmitral E- and A-wave overlapping predicted prognosis in patient with heart failure with preserved ejection
Authors: Iwakura K , Tanaka N , Okada M , Okamura A , Watanabe H , Seo M , Hayashi T , Yano M , Yamada T , Yasumura Y , Hikoso S , Okada K , Nakatani D , Sotomi Y , Sakata Y 
Published: October 2024

Abstract

Background
The impact of heart rate (HR) variability on clinical outcomes in patients with heart failure with preserved ejection fraction (HFpEF) is not fully understood. Variations in HR may affect transmitral blood flow and consequently left ventricular filling and left atrial pressure. Changes in HR can cause the transmitral E-wave and A-wave to merge at higher HRs, while their interval lengthens at slower HRs (Figure: left). A recent study (Izumida. ESC Heart Fail. 2020;7:3231) demonstrated that the degree of overlap or interval between E- and A-waves can be estimated using resting HR and the deceleration time of the E-wave (DcT) on Doppler echocardiography.

Purpose
This study aims to investigate the relationship between the estimated overlap length between E- and A-waves and prognosis in patients with HFpEF.

Methods
Echocardiography was performed before hospital discharge in 398 patients (80±9 years, 59.0% female) hospitalized for decompensated HFpEF who were registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) registry. The overlap length between E- and A waves was estimated using the formula [6.2 × HR (bpm) + 0.81 × DcT (ms) -589 (ms)] as previously described (a negative value means distance between two waves). Patients were divided into four groups based on quartiles of overlap length (Q1 to Q4, with Q4 representing the highest overlap length) and followed for a median duration of 759 days (interquartile range: 370, 1107 days) to observe all-cause mortality.

Results
The estimated overlap length in the study patients was -167±85 ms, and 105 deaths occurred during follow-up. The overlap length was selected as an independent predictor for all-cause mortality by Cox proportional hazards regression analysis (p=0.04), whereas HR or DcT was not. Kaplan-Meier curves indicated the difference in all-cause mortality among 4 groups (Figure: Right, p=0.02 by log-rank test), and the Q4 group (335 to -123ms) showed significantly higher mortality than the Q2 (-124 to -173 ms, p=0.03).

Conclusion
The overlap length of E and A predicted mortality in HFpEF patients, and the presence of overlap or shorter interval were associated with higher mortality. Optimal HR based on overlap length may be a new target for HFpEF therapy.Figure 1