bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Diagnosis to Ablation Time on Recurrence of Atrial Fibrillation and Clinical Outcomes After Catheter Ablation: A Systematic Review and Meta-Analysis With Reconstructed Time-to-Event Data
Authors: Amin Ahmed Mazen , Elbenawi Hossam , Khan Ubaid , Almaadawy Omar , Turkmani Mustafa , Abdelmottaleb Wael , Essa Mohammed , Abuelazm Mohamed , Abdelazeem Basel , Asad Zain Ul Abideen , Deshmukh Abhishek , Link Mark S. , DeSimone Christopher V. 
Published: February 2025

BACKGROUND:
Current clinical guidelines emphasize the significance of rhythm control with catheter ablation but lack guidance on the timing of atrial fibrillation (AF) ablation relative to the diagnosis time. We aim to investigate the latest evidence on the impact of diagnosis to ablation time (DAT) on clinical outcomes after AF ablation.

METHODS:
We searched PubMed, Web of Science, Scopus, Embase, and Cochrane Central Register of Controlled Trials through August 2024. Pairwise, prognostic, and reconstructed time-to-event data meta-analyses were conducted using R V. 4.3.1. Our primary end point was time to first AF recurrence, with secondary end points of all-cause mortality, tamponade, stroke, and heart failure.

RESULTS:

Our cohort included 23 studies with 43 711 patients. Shorter DAT was significantly associated with reduced AF recurrence across both paroxysmal and persistent AF subgroups (
P
<0.01). There was a significant decrease in benefit for paroxysmal AF over time and a slight decrease in benefit for persistent AF over time. However, the benefit remained significant in both over time. DAT per year was significantly associated with a 10% increased risk of AF recurrence. Reconstructed Kaplan-Meier analysis showed that DAT >1 year was significantly associated with a 70% increased risk of AF recurrence in paroxysmal AF and 30% in persistent AF. DAT ≤1 year was significantly associated with decreased all-cause mortality (
P
<0.01) and showed a trend toward an association with a lower incidence of stroke (
P
=0.08). However, there was no significant difference in heart failure between DAT ≤1 year and DAT >1 year.

CONCLUSIONS:
Early ablation is more beneficial in paroxysmal AF, with a notable decrease in benefit over time, while in persistent AF, the benefit remains significant but slightly decreases over time. Shorter DAT was significantly associated with decreased all-cause mortality and showed a trend toward an association with a lower incidence of stroke.

REGISTRATION:

URL:
https://www.crd.york.ac.uk/prospero/display_record.php?
; Unique identifier: CRD42024525542.
Global and Temporal Trends in Utilization and Outcomes of Implantable Cardioverter Defibrillators in Hypertrophic Cardiomyopathy
Authors: Abdelfattah Omar M. , Sayed Ahmed , Al-Jwaid Ahmed , Hassan Ahmed , Abu Jazar Deaa , Narayanan Arun , Link Mark S. , Martinez Matthew W. 
Published: February 2025

BACKGROUND:
Over the past decades, hypertrophic cardiomyopathy has become a contemporary treatable disease. However, limited data exist on the global trends of implantable cardioverter defibrillator (ICD) utilization and its impact on mortality/morbidity burden reduction.

METHODS:
Electronic databases were systematically searched up to March 2024 for studies reporting on ICD utilization rates in hypertrophic cardiomyopathy. A random effects model was used to pool study estimates across time-era, geographic region, and age group. Primary outcome was global trends in ICD utilization. Secondary outcomes included trends of sudden cardiac death, appropriate/inappropriate shocks, and ICD-related complications.

RESULTS:

In total, 234 studies (N=92 500, 514 748 patient-years) met inclusion criteria. Mean age was 46.2 (12.4) years and 37.49% were women. A total of 12 139 patients (16.43%) received an ICD over 429 766 person-years of follow-up, with an ICD implantation rate of 2.79%/y ([95% CI, 2.35%–3.32%] I²=97.80%). Rates of ICD implantation steadily increased over time from 1990 (1.09%) to 2021 (4.01%;
P
=0.002), with noticeable geographic variation (
P
=0.008). The overall rate of appropriate ICD discharges and ICD-related complications was 3.44%/y ([95% CI, 3.08%–3.84%] I²=88.40%) and 1.98%/y ([95% CI, 1.52%–2.59%] I²=90.44%), respectively, with no significant trend over time. The overall rate of inappropriate discharges was 3.58%/y ([95% CI, 3.08%–4.16%] I
2
=88.03%), and declined significantly over time (
P
=0.044). There was a significant decline in the rates of sudden cardiac death from 1990 (0.84%/y) to 2020 (0.31%/y).

CONCLUSIONS:
Dramatic increases in ICD utilization have occurred, representing a 3.7-fold increase, with appropriate therapies occurring in 3.44%/y. In parallel a significant reduction in sudden cardiac death was observed, but there are insufficient data to demonstrate that a causative relationship exists. Geographic disparities in ICD utilization were evident, highlighting the need to improve access to specialized care for patients with hypertrophic cardiomyopathy. Geographic disparities in ICD utilization were evident, highlighting the need to improve access to specialized care for patients with hypertrophic cardiomyopathy.

REGISTRATION:

URL:
https://www.crd.york.ac.uk/PROSPERO/
; Unique identifier: CRD42023407126
Cardiac Gene Therapy With Phosphodiesterase 2A Limits Remodeling and Arrhythmias in Mouse Models of Heart Failure
Authors: Kamel Rima , Bourcier Aurélia , Margaria Jean Piero , Jin Valentin , Varin Audrey , Hivonnait Agnès , Mercier‐Nomé Françoise , Mika Delphine , Ghigo Alessandra , Charpentier Flavien , Algalarrondo Vincent , Hirsch Emilio , Fischmeister Rodolphe , Vandecasteele Grégoire , Leroy Jérôme 
Published: February 2025

Background
PDE2 (phosphodiesterase 2) is upregulated in human heart failure. Cardiac PDE2‐transgenic mice are protected against contractile dysfunction and arrhythmias in heart failure but whether an acute elevation of PDE2 could be of therapeutic value remains elusive. This hypothesis was tested using cardiac PDE2 gene transfer in preclinical models of heart failure.

Methods and Results
C57BL/6 male mice were injected with serotype 9 adeno‐associated viruses encoding for PDE2A. This led to a ≈10‐fold rise of PDE2A protein levels that affected neither cardiac structure nor function in healthy mice. Two weeks after inoculation with serotype 9 adeno‐associated viruses, mice were implanted with minipumps delivering either NaCl, isoproterenol (60 mg/kg per day), or isoproterenol and phenylephrine (30 mg/kg per day each) for 2 weeks. In mice injected with serotype 9 adeno‐associated viruses encoding for LUC (luciferase), isoproterenol or isoproterenol+phenylephrine infusion induced left ventricular hypertrophy, decreased ejection fraction unveiled by echocardiography, and promoted fibrosis and apoptosis assessed by Masson's trichrome and Tunel, respectively. Furthermore, inotropic responses to isoproterenol of ventricular cardiomyocytes isolated from isoproterenol+phenylephrine‐LUC mice loaded with 1 μmol/L Fura‐2AM and stimulated at 1 Hz to record calcium transients and sarcomere shortening were dampened. Spontaneous calcium waves at the cellular level were promoted as well as ventricular arrhythmias evoked in vivo by catheter‐mediated ventricular pacing after isoproterenol (1.5 mg/kg) and atropine (1 mg/kg) injection. However, increased PDE2A blunted these adverse outcomes evoked by sympathomimetic amines.

Conclusions
Cardiac gene therapy with PDE2A limits left ventricle remodeling, dysfunction, and arrhythmias evoked by catecholamines, providing evidence that increasing PDE2A activity acutely could prevent progression toward heart failure.
Effectiveness of an Impella Versus Intra‐Aortic Balloon Pump in Patients Who Received Extracorporeal Membrane Oxygenation
Authors: Nishimoto Yuji , Ohbe Hiroyuki , Nakata Jun , Takiguchi Toru , Nakajima Mikio , Sasabuchi Yusuke , Isogai Toshiaki , Matsui Hiroki , Sato Yukihito , Watanabe Tetsuya , Yamada Takahisa , Fukunami Masatake , Yasunaga Hideo 
Published: February 2025

Background
It is unclear whether an intra‐aortic balloon pump (IABP) or percutaneous ventricular assist device (Impella) in combination with extracorporeal membrane oxygenation (ECMO) is better.

Methods
Using the Japanese Diagnosis Procedure Combination database from September 2016 to March 2022, we identified inpatients who received an Impella or IABP in combination with ECMO (ECPella or ECMO+IABP group, respectively). The primary outcome was in‐hospital mortality, and the secondary outcomes included the length of hospital stay, length of ECMO, total hospitalization cost, complications, and durable mechanical circulatory support implantations. Propensity score matching was performed to compare the outcomes between the groups.

Results
Of 14 319 eligible patients, 590 (4.1%) received ECPella and 13 729 (96%) received ECMO+IABP. The mean age of patients was 65 years, 77% were men, and 57% had acute coronary syndrome. After propensity score matching, the patient characteristics were well balanced between the groups. The 14‐day mortality rate was lower in the ECPella group than in the ECMO+IABP group (28.0% versus 36.8%; risk difference, −8.2% [95% CI, −13.8 to −2.7]), whereas there was no significant difference in in‐hospital mortality between the groups (58.3% versus 56.6%; risk difference, 2.4% [95% CI, −3.5 to 8.2]). The ECPella group had a higher total hospitalization cost, increased renal replacement therapy during hospitalization, and more durable mechanical circulatory support implantations than the ECMO+IABP group.

Conclusions
This nationwide inpatient database study showed no significant difference in in‐hospital mortality between the groups, but ECPella was associated with a higher total hospitalization cost, increased renal replacement therapy during hospitalization, and more durable mechanical circulatory support implantations than ECMO+IABP.
Impact of Silent Cerebral Embolism during and after Left Atrial Appendage Occlusion on Long‐Term Cognitive Function
Authors: Wang Kexin , Wang Zhe , Jin Caiyi , Xu Mingjia , Li Mingfang , Liu Hailei , Wang Zidun , Chen Hongwu , Ju Weizhu , Chen Minglong 
Published: February 2025

Background
Left atrial appendage occlusion (LAAO) was associated with a high incidence of procedure‐related silent cerebral embolism (SCE). There are limited data regarding the long‐term cognitive trajectory of patients undergoing LAAO. The aim of our study was to comprehensively assess the acute and long‐term impact of SCE during and after LAAO.

Methods
Consecutive patients with atrial fibrillation referred for LAAO from the First Affiliated Hospital with Nanjing Medical University between February 2021 and February 2023 were included. All patients underwent magnetic resonance imaging and cognitive assessments before and within 48 hours after the procedure. These evaluations were also repeated at 45‐day, 3‐month, 6‐month, and 1‐year follow up.

Results

Out of 75 patients included in the final analysis, 29 (38.7%) patients suffered from new SCE during LAAO. Patients with SCE exhibited a significant decline in cognitive function (Mini‐Mental State Examination) immediately after the procedure (
P
<0.001), which was not reversible during 1‐year follow‐up (
P
<0.001). Additionally, with time going on, the gap in cognitive function between patients with and without SCE became wider (SCE × 1 year: B=−4.81 [95% CI, −5.58 to −4.05];
P
<0.001). New‐onset SCE was detected in 11 (14.7%) patients during the follow‐up magnetic resonance imaging, which also showed a decline in cognitive function (
P
=0.004). The results in Montreal Cognitive Assessment scores were consistent with Mini‐Mental State Examination.

Conclusions
LAAO‐related SCE is associated with a marked impairment in cognitive function immediately after the procedure and is irreversible over a 1‐year follow‐up. New magnetic resonance‐detected SCE during follow‐up after LAAO would also be associated with a decline in cognitive function.
Temporal Trends in Mortality and Hospitalization Risk in Patients With Heart Failure According to the Hospital Frailty Risk Score
Authors: Abassi Noor K. , Nouhravesh Nina , Elmegaard Mariam , Austreim Marte , Zahir Deewa , Garred Caroline Hartwell , Butt Jawad H. , Andersen Camilla Fuchs , Strange Jarl E. , Sindet‐Pedersen Caroline , Christensen Daniel M. , Fosbøl Emil , Andersson Charlotte , Køber Lars , Schou Morten 
Published: February 2025

Background
Heart failure (HF) and frailty often coexist. However, it is unknown how the interplay between HF and frailty at HF onset impacts prognosis of frail patients with HF and how this has evolved over time.

Methods and Results
We identified 131 235 patients with new‐onset HF (median age 74 years, 39.7% women) from Danish nationwide registers in 1999 to 2017. Stratification according to the Hospital Frailty Risk Score resulted in (1) 102 635 (78%) nonfrail, (2) 26 054 (20%) moderately frail, and (3) 2609 (2%) severely frail patients. The proportion of moderately frail patients increased from 13.2% to 24.9%. Five‐year absolute risks of all‐cause mortality, HF hospitalization, and non‐HF hospitalization were calculated using the Kaplan‐Meier and Aalen‐Johansen estimators. From 1999 to 2002 to 2003 to 2017, all‐cause mortality risk (95% CI) declined from 56.4% (55.8%–57.0%) to 33.3% (32.6%–34.1%), 79.8% (78.5%–81.0%) to 58.6% (57.2%–60.1%), and 90.8% (85.6%–96.0%) to 79.8% (76.4%–83.2%) in nonfrail, moderately frail, and severely frail patients, respectively. HF hospitalization risk remained almost constant over the study period. Non‐HF hospitalization risk declined from 74.0% (73.5%–74.5%) to 65.8% (65.0%–66.5%) in nonfrail patients and remained stable overall in moderately frail and severely frail patients over the study period.

Conclusions
We observed an increase in frail patients. Mortality decreased for all frailty groups but remained high for severely frail patients. These findings indicate the need for further evidence on the optimization of care for frail patients with HF, and future research should address the development of comprehensive management strategies, integrating frailty assessment into standard clinical care and focused care for older patients with HF.
Proteome‐Wide Mendelian Randomization Identifies Therapeutic Targets for Abdominal Aortic Aneurysm
Authors: Zhang Ka , Liu Yuan , Mao Aiqin , Li Changzhu , Geng Li , Kan Hao 
Published: February 2025

Background
The proteome is a key source of therapeutic targets. We conducted a comprehensive Mendelian randomization analysis across the proteome to identify potential protein markers and therapeutic targets for abdominal aortic aneurysm (AAA).

Methods and Results
Our study used plasma proteomics data from the UK Biobank, comprising 2923 proteins from 54 219 individuals, and from deCODE Genetics, which measured 4907 proteins across 35 559 individuals. Significant proteomic quantitative trait loci were used as instruments for Mendelian randomization. Genetic associations with AAA were sourced from the AAAgen consortium, a large‐scale genome‐wide association study meta‐analysis involving 37 214 cases and 1 086 107 controls, and the FinnGen study, which included 3869 cases and 381 977 controls. Sequential analyses of colocalization and summary‐data‐based Mendelian randomization were performed to verify the causal roles of candidate proteins. Additionally, single‐cell expression analysis, protein–protein interaction network analysis, pathway enrichment analysis, and druggability assessments were conducted to identify cell types with enriched expression and prioritize potential therapeutic targets. The proteome‐wide Mendelian randomization analysis identified 34 proteins associated with AAA risk. Among them, 2 proteins, COL6A3 and PRKD2, were highlighted by colocalization analysis, summary‐data‐based Mendelian randomization, and the heterogeneity in an independent instrument test, providing the most convincing evidence. These protein‐coding genes are primarily expressed in macrophages, smooth muscle cells, and mast cells within abdominal aortic aneurysm tissue. Several causal proteins are involved in pathways regulating lipid metabolism, immune responses, and extracellular matrix organization. Nine proteins have already been targeted for drug development in diabetes and other cardiovascular diseases, presenting opportunities for repurposing as AAA therapeutic targets.

Conclusions
This study identifies causal proteins for AAA, enhancing our understanding of its molecular cause and advancing the development of therapeutics.
Epicardial Fat Tissue: A Potential Marker for Coronary Microvascular Dysfunction
Authors: Abusnina Waiel , Merdler Ilan , Cellamare Matteo , Chitturi Kalyan R. , Chaturvedi Abhishek , Feuerstein Irwin M. , Zhang Cheng , Ozturk Sevket Tolga , Deksissa Teshome , Sawant Vaishnavi , Lopez Kassandra , Lupu Lior , Haberman Dan , Ben‐Dor Itsik , Satler Lowell F. , Waksman Ron , Hashim Hayder D. , Case Brian C. 
Published: February 2025

Background
Coronary microvascular dysfunction (CMD), which mimics symptoms of obstructive coronary artery disease, has significant prognostic implications. While epicardial adipose tissue normally has a protective role, increased epicardial adipose tissue is associated with inflammation and may contribute to CMD. However, a direct correlation remains unclear. We aimed to investigate this association.

Methods and Results

The CMDR (Coronary Microvascular Disease Registry) is a prospective, 2‐center registry that is enrolling patients with angina and nonobstructive coronary artery disease who underwent invasive hemodynamic assessment of the coronary microvasculature. Patients with chest computed tomography within 1 year of CMD evaluation were included. We measured epicardial fat volume (EFV) and calculated the EFV index. Logistic regression analysis was used to investigate the association between EFV and EFV index to CMD. Our study included 130 CMDR patients with associated chest CT; 35 were diagnosed with CMD. The CMD‐negative patients were younger than the CMD‐positive patients (58.52±11.97 versus 63.37±9.56 years;
P
=0.033), with numerically fewer women (64.2% versus 74.3%;
P
=0.279). Univariate regression analysis demonstrated a statistically significant association between EFV index and CMD diagnosis (odds ratio, 1.037 [95% CI, 1.014–1.063];
P
=0.003), while no significance was observed for EFV (odds ratio, 1.006 [95% CI, 0.995–1.017];
P
=0.292).

Conclusions
Our results suggest a strong association between EFV index (a significant risk factor) and the presence of CMD. Future studies involving larger cohorts are needed to confirm the association of epicardial adipose tissue with CMD and investigate therapeutic targets to prevent CMD.

Registration

URL:
https://www.clinicaltrials.gov
; unique identifier: NCT05960474.
Measuring the impact of COVID-19 pandemic on the activeness, efficiency and international collaboration of clinical trials
Authors: Zhao Wenjing , Yuan Chi , He Zixuan , Du Jian 
Published: February 2025

Abstract
The disruption of clinical trials during the COVID-19 pandemic has been discussed widely. But no systemically study has quantitatively examined the multi-dimensional effect of COVID-19 on the clinical trials of non-COVID-19 diseases under a well-recognized disease classification system. By acquiring over 380,000 clinical trials from ClinicalTrials.gov and Dimensions, and automatically mapping trials with the WHO Global Health Estimates (GHE) cause category, this study explores the effect of COVID-19 on trials’ activeness, efficiency, and international collaboration. Beyond a global perspective, the granular comparative analysis using the USA, China, Japan, the UK as representative cases are conducted. Utilizing an interrupted time series model, we find that while aggregate number of trial registrations has remained relatively stable, there is a notable crowding-out effect for non-COVID-19 diseases, affecting both non-communicable and communicable diseases. Interestingly, despite heightened focus on COVID- 19 research, trial efficiency for other diseases remained largely unaffected. COVID-19 prompted increased global collaboration in clinical research. Through further categorization of sponsorship type and identification of digitized trials by text-mining analysis, we summarized and validated three potential factors to shed light on the observed effects of COVID-19 on clinical studies. Additionally, the valuable insights and essential lessons in managing unprecedented pandemics are discussed.

Peer Review
https://www.webofscience.com/api/gateway/wos/peer-review/10.1162/qss_a_00354
The Marginalized Speak Back: Suffering, Survival, and Solidarity in the Oral Narratives of Left-Behind Families of Slain Victims of the Philippine Drug War
Authors: Palaspas Francis Louie F. , Serquiña Oscar T. 
Published: February 2025

Abstract
Former Philippine President Rodrigo Duterte is infamous for his war on drugs campaign, commonly known as Oplan Tokhang, which killed countless members of urban poor communities and left numerous families suffering the consequences of losing a loved one to state violence. This article centers the narratives of ten (10) mothers and wives whose loved ones perished in Duterte’s drug war and who eventually joined the non-government organization called Rise Up for Life and for Rights that opposes drug-related extrajudicial killings and violations. Guided by Ernest Bormann’s Symbolic Convergence Theory, it brings to the surface the prevailing characters, settings, and plotlines embedded in the oral narratives of these left-behind women. Out of these converging elements, it further crafts the rhetorical vision of these women in relation to the brutal death of their beloved and to their own struggles and sufferings. This article throws into light a rhetorical vision that accounts for how families of the victims are no longer simply mothers and wives incapable of resistance and vulnerable to all forms of injustices. Informed, empowered, and open to change, they have realized and actively practice a kind of political agency in the wake of the adversities they faced during Duterte’s presidency and continue to face at present time.
Comparison of Long-Term Outcomes Between Conversion to Open and Laparoscopic Subtotal Cholecystectomy in the Difficult Gallbladder: A Single-Center Retrospective Study
Authors: Badve Shivani B. , Turcotte Justin , Brennan Jane C. , Klune John , Feather Cristina B. , Rehrig Scott , Kulkarni Shreyus S. 
Published: February 2025

Background A difficult laparoscopic cholecystectomy (LC) confers an increased risk of bile duct injury. Traditionally, surgeons convert to open cholecystectomy (OC) as a bailout procedure for safer dissection. Laparoscopic subtotal cholecystectomy (LSC) has recently gained favor with comparable short-term complication rates, but differences in long-term outcomes remain unknown. We sought to compare long-term biliary outcomes between OC and LSC. Study Design We performed a single-center retrospective cohort study of adults who underwent non-elective LC converted to OC or LSC due to difficult dissection from 1/1/2015 to 12/31/2019. The primary outcome was a composite measure of postoperative biliary events, and we used time-to-event analysis to compare the 2 groups. We evaluated secondary outcomes using Chi-squared or independent t-tests as appropriate. Results Of 1089 patients who underwent non-elective LC, 68 (6%) underwent a bailout procedure (30 OC vs 38 LSC). There were no differences in demographics or comorbidities between the groups. Most patients (84%) had acute cholecystitis. Average follow-up times were 40 ∓ 29 months in OC and 54 ∓ 21 months in LSC. Biliary events occurred in 13 total patients (19%) with OC most commonly suffering bile leak (17%) and LSC most commonly having choledocholithiasis (11%). Kaplan-Meier analysis demonstrated no significant difference in biliary events between the groups ( P = 0.71). Secondary outcomes were all similar between groups, except LSC had a shorter length of stay (2.9 ∓ 2.3 vs 5.1 ∓ 3.6 days, P = 0.002). Conclusions OC and LSC demonstrated comparable long-term biliary outcomes. In a difficult LC, surgeons may perform either bailout procedure to safely manage the gallbladder.