bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proton Pump Inhibitors Use in Patients With Ischemic Stroke on Dual Antiplatelet Therapy at Low Risk of Upper Gastrointestinal Bleeding
Authors: Baik Minyoul , Jeon Jimin , Heo Seok‐Jae , Kim Jinkwon , Yoo Joonsang 
Published: December 2024

Background
Current guidelines lack recommendations regarding the use of proton pump inhibitors (PPIs) for preventing upper gastrointestinal bleeding (UGIB) among patients at low risk for UGIB treated with dual antiplatelet therapy for ischemic stroke (IS). Our objective was to assess the effectiveness of PPIs in lowering the risk of significant UGIB in this patient group.

Methods and Results

A retrospective cohort study was conducted involving patients at low risk for UGIB admitted for IS between 2014 and 2018 and treated with dual antiplatelet therapy. The study used a nationwide claims database in Korea. The primary end point was significant UGIB during 12 months after IS. To evaluate the risk of significant UGIB based on PPI use, we performed a multivariable Cox regression analysis. Subgroup analyses and propensity score matching analysis were conducted for validation. Among 96 722 patients with IS at low risk for UGIB who were on dual antiplatelet therapy (mean age, 67.0 years; men: 63.0%), 16 084 (16.6%) were treated with PPIs. During 12 months of follow‐up, 325 patients experienced significant UGIB, and 479 experienced any UGIB. PPI use was associated with a reduced risk of significant UGIB (hazard ratio, 0.63 [95% CI, 0.45–0.89];
P
=0.009). This association was consistent in the subgroup and propensity score matching analyses.

Conclusions
In patients with IS receiving dual antiplatelet therapy, PPI use reduced the risk of significant UGIB by 37% on average, even among low‐risk patients. However, the use of PPIs in this patient group was limited, highlighting the need for additional prospective studies.
Hyperkalemia and the Risks of Adverse Cardiovascular Outcomes in Patients With Chronic Kidney Disease
Authors: Agiro Abiy , Mu Fan , Cook Erin , Greatsinger Alexandra , Chen Jingyi , Zhao Angela , Louden Elaine , Colman Ellen , Desai Pooja , Chertow Glenn M. 
Published: December 2024

Background
This real‐world evidence study compared risks of cardiovascular events in hospital settings among patients with chronic kidney disease (CKD) with and without hyperkalemia.

Methods and Results

Adults with CKD stages 3b/4 with and without hyperkalemia were identified from Optum's deidentified Market Clarity Data (January 2016–August 2022). Patients with hyperkalemia were exact and propensity score matched to patients without hyperkalemia. The index date was the first CKD stage 3b/4 diagnosis with ≥1 hyperkalemia diagnosis and ≥1 serum potassium >5.0 mmol/L in the preceding 12 months (baseline) for patients with hyperkalemia and a randomly selected CKD stage 3b/4 diagnosis for controls. Cardiovascular composite end points included major adverse cardiovascular events plus (a composite end point of all‐cause mortality, myocardial infarction, stroke, or heart failure) and cardiac arrhythmias (a composite end point of new onset atrial fibrillation and other atrial and ventricular arrythmias), all in the hospital setting. We compared cardiovascular events between cohorts using cause‐specific Cox proportional hazards regression. The study included 5301 matched pairs in the analysis of major adverse cardiovascular events plus and 5564 in the analysis of arrhythmia. Cardiovascular events were more likely among patients with hyperkalemia relative to those without hyperkalemia, with the risk of major adverse cardiovascular events plus increased by 32% (23%–40%) and the risk of arrhythmia increased by 59% (44%–75%; both
P
<0.001).

Conclusions
Among patients with CKD stages 3b/4, patients with hyperkalemia experienced significantly higher risks of major adverse cardiovascular events and arrhythmia in hospital settings relative to patients without hyperkalemia.
Diagnostic Accuracy of Computational Fluid Dynamics‐Based Fractional Flow Reserve Derived From Coronary Angiography: The ACCURATE Study
Authors: Jiang Jun , Hu Yumeng , Li Changling , Dong Liang , Xu Jian , Tang Lijiang , Jiang Wenbing , Du Changqing , Jiang Xuejun , Lyu Yongnan , Leng Xiaochang , Li Chengguang , Koo Bon‐Kwon , Xiang Jianping , Ge Junbo , Wang Jian’an 
Published: December 2024

Background
Although fractional flow reserve (FFR) is the contemporary standard to detect hemodynamically significant coronary stenosis, it remains underused for the need of pressure wire and hyperemic stimulus. Coronary angiography‐derived FFR could break through these barriers. The aim of this study was to assess the feasibility and performance of a novel diagnostic modality deriving FFR from invasive coronary angiography (AccuFFRangio) for coronary physiological assessment.

Methods and Results

The ACCURATE (Angiography‐Derived Fractional Flow Reserve for Functional Evaluation of Coronary Artery Disease) study was a prospective, multicenter study conducted at 5 centers. Patients who had at least 1 lesion with a diameter stenosis of 30% to 90% were eligible. AccuFFRangio was measured on site in real time and compared with invasive FFR measurements in a blinded fashion. Primary end point was the diagnostic accuracy of AccuFFRangio in identifying functional relevant lesions. Between November 2020 and June 2021, pairwise analyses of AccuFFRangio and FFR were performed in 304 coronary arteries. AccuFFRangio showed good correlation (
r
=0.89;
P
<0.001) and agreement (mean difference: 0.01±0.06) with FFR. The diagnostic accuracy was 95.07% (95% CI, 91.99%–97.21%), which were significantly exceeded the prespecified target value (
P
<0.001). The sensitivity, specificity, and area under the receiver operating characteristic curve of 95.83% (95% CI, 89.67%–98.85%), 94.71% (95% CI, 90.73%–97.33%), and 0.972 (95% CI, 0.947–0.988), respectively.

Conclusions
AccuFFRangio derived from coronary angiography alone has high diagnostic accuracy, sensitivity, and specificity compared with FFR. AccuFFRangio bears the potential for increasing the adoption of functional assessment of coronary artery stenosis and improving the use of physiological guided decision‐making.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04814550.
Echocardiographic Changes Following Surgical Myectomy in Severely Symptomatic Obstructive Hypertrophic Cardiomyopathy: Insights From the SPIRIT‐HCM Study
Authors: Desai Milind Y. , Szpakowski Natalie , Tower‐Rader Albree , Bittel Barb , Fava Agostina , Ospina Susan , Xu Bo , Thamilarasan Maran , Mentias Amgad , Smedira Nicholas G. , Popovic Zoran B. 
Published: December 2024

Background
In obstructive hypertrophic cardiomyopathy, myectomy improves symptoms, quality of life, and left ventricular (LV) outflow tract gradients. We prospectively evaluated the temporal changes in various echo parameters after myectomy.

Methods and Results

In 173 adults with obstructive hypertrophic cardiomyopathy (53±10 years, 63% men) who underwent myectomy between March 2017 and June 2020, clinical and blinded echo assessment (before and at 12±6 months follow‐up) was performed prospectively (SPIRIT‐HCM [Quality of Life and Functional Capacity Following Septal Myectomy in Obstructive Patients With Hypertrophic Cardiomyopathy]). Changes in echocardiographic parameters (left atrial volume index,
E
/
e
′, LV outflow tract gradients, along with average LV global longitudinal strain on apical 2‐, 3‐, and 4‐chamber views and regional LV strain from apical 4‐chamber view) were measured in 126 patients. There was significant improvement in left atrial volume index (−6.9 mL/m
2
[95% CI, 4–9.7]),
E
/
e
′ (−2.9 [95% CI, −2.7 to −4.1]) and peak LV outflow tract gradient (−94 mm Hg [95% CI −87 to −100]) from baseline to follow‐up (both
P
<0.001). There was no improvement in basal (0.91% [95% CI, −0.15 to 1.97],
P
=0.09) and midseptal (−0.98% [95% CI, −1.93 to 0.02],
P
=0.05) LV strain, worsening in apical septal strain (−4.5% [95% CI, −5.9 to −3.0],
P
<0.001) and an improvement in LV free wall strain (2.3% [95% CI, 0.67–3.9],
P
<0.001), with no change in overall LV‐global longitudinal strain (0.47% [95% CI, −0.43 to 1.37],
P
=0.30). There was no correlation between change in LV‐global longitudinal strain and change in 6‐minute walk time (r=0.12,
P
=0.24) or Kansas City Cardiomyopathy Questionnaire summary score change (r=0.02,
P
=0.85), whereas it was significantly associated with change in
E
/
e
′ (r=0.29,
P
=0.003).

Conclusions
In patients with obstructive hypertrophic cardiomyopathy, myectomy improved various echocardiography parameters at 1‐year; however, LV‐global longitudinal strain remained unchanged.

Registration

URL:
https://clinicaltrials.gov
; Unique identifier: NCT03092843.
Atherothrombotic Outcomes After Sodium‐Glucose Cotransporter 2 Inhibitors Versus Dipeptidyl Peptidase‐4 Inhibitors in Patients With Type 2 Diabetes: A Territory‐Wide Retrospective Cohort Study
Authors: Ng Pauline Yeung , Ng Andrew Kei‐Yan , Ip April , Sin Wai Ching , Yiu Kai‐Hang 
Published: December 2024

Background
This study compared the risks of atherothrombotic major adverse cardiovascular events in patients with type 2 diabetes taking SGLT2 (sodium‐glucose cotransporter 2) inhibitors to those taking DPP‐4 (dipeptidyl peptidase‐4) inhibitors.

Methods and Results

All adult patients (≥18 years of age) with type 2 diabetes and newly prescribed with SGLT2 inhibitors or DPP‐4 inhibitors across all public hospitals in Hong Kong between January 2015 and December 2019 were included. Patients were propensity matched in a 1:1 ratio using a caliper distance of 0.2 without replacement. The primary outcome was atherothrombotic major adverse cardiovascular events as a composite outcome of cardiovascular mortality, nonfatal stroke, and nonfatal myocardial infarction. Time‐to‐first event analysis was conducted using a univariable Cox proportional hazards model. Primary and secondary analyses were repeated using stabilized inverse probability weighting and propensity score adjustment in the complete case cohort. A total of 20 642 patients (10 321 SGLT2 inhibitors versus 10 321 DPP‐4 inhibitors) were included in the final analysis. The mean age was 59±11 years, and 13 142 (63.7%) were men. The median follow‐up period was 2.9 years. The use of SGLT2 inhibitors was associated with a significant reduction in atherothrombotic major adverse cardiovascular events (453 [4.4%] versus 719 [7.0%]; hazard ratio, 0.64 [95% CI, 0.57–0.72];
P
<0.001) compared with DPP‐4 inhibitors. SGLT2 inhibitors were independently associated with reduced all‐cause mortality, cardiovascular mortality, stroke, myocardial infarction, and incident dialysis (all
P
values <0.001).

Conclusions
SGLT2 inhibitors in patients with diabetes were independently associated with reduction in atherothrombotic major adverse cardiovascular events, all‐cause mortality, cardiovascular mortality, myocardial infarction, stroke, and incident dialysis, compared with DPP‐4 inhibitors.
Modulation of Abnormal Vasoconstriction Through 2‐Hydroxyisobutyrylation of Tropomyosin 3 Lys141: Targeting Histone Deacetylase 3 as a Key Approach
Authors: Pang Pan‐Pan , Liu Jiang‐Xin , Su Wen‐Bin , Gao Wen‐Cong , Qiao Guan‐Rong , Yuan Jing , Zheng Yong‐Tang , Zheng Chang‐Bo 
Published: December 2024

Background
TPM3 (tropomyosin 3) is an actin‐binding protein in vascular smooth muscle cells, where posttranslational modifications critically regulate its actin affinity, influencing cardiovascular function. Emerging evidence suggests that Khib (2‐hydroxyisobutyrylation) plays a significant role in the cardiovascular system. Histone deacetylase 3 (HDAC3) serves as an “eraser” of Khib marks. However, the impact of TPM3 de‐2‐hydroxyisobutyrylation on vascular contraction remains unclear.

Methods and Results
In this study, we employed mouse models and in vitro experiments to elucidate the mechanism by which phenylephrine‐induced HDAC3 activation drives vasoconstriction via de‐2‐hydroxyisobutyrylation of TPM3. Our findings demonstrate that phenylephrine triggers HDAC3 nuclear export and promotes its interaction with TPM3, resulting in decreased Khib modification and enhanced vasoconstriction. Coimmunoprecipitation experiments confirmed that phenylephrine reduces Khib levels on TPM3 in mouse aorta. Additionally, ex vivo vascular tension assays using mouse aortic rings revealed that treatment with the Khib donor, ethyl 2‐hydroxyisobutyrate, induces endothelium‐independent vasodilation and ameliorates hypertensive vascular dysfunction. Molecular docking and kinetic simulations identified Lys141 of TPM3 as the primary site targeted by HDAC3‐mediated de‐2‐hydroxyisobutyrylation. This was further validated by adenoviral transfection of isolated blood vessels with a Lys141‐mutated TPM3 construct, which abolished the effects of HDAC3 on TPM3 Khib modification and vascular contractility.

Conclusions
These findings underscore the critical role of TPM3 de‐2‐hydroxyisobutyrylation in vasoconstriction and suggest that modulating this posttranslational modification could provide a novel therapeutic strategy for hypertensive vascular dysfunction.
Optimal Definition and Risk Stratification in Prediabetes With Stable Coronary Heart Disease: A Prospective Cohort Study
Authors: Song Chenxi , Qiao Zheng , Cheng Jiaxi , Zhang Yuze , Liu Weida , Yuan Sheng , He Jining , Song Yanjun , Bian Xiaohui , Lin Zhangyu , Fu Rui , Wang Chunyue , Liu Qianqian , Feng Lei , Tao Jin , Dou Kefei 
Published: December 2024

Background
The optimal definition and risk stratification approach to identify high‐risk patients with prediabetes and stable coronary heart disease has not been well studied to date. The objective of the current study is to compare the prognostic value of different definitions of prediabetes, and to explore the role of “very‐high‐risk” (VHR) criteria according to the 2018 American Heart Association/American College of Cardiology cholesterol guideline in the risk stratification of patients with prediabetes and stable coronary heart disease.

Methods and Results
This prospective large‐cohort study enrolled a total of 7930 patients with stable coronary heart disease. Prediabetes was defined according to various guidelines and further classified on the basis of the VHR criteria according to the 2018 American Heart Association/American College of Cardiology guideline. The primary end point was major adverse cardiovascular events (MACEs), which was defined as the composite end point of cardiac death, nonfatal acute myocardial infarction, and stroke.

During a median of 3 years’ follow‐up, a total of 256 MACEs occurred. Prediabetes defined according to the World Health Organization/International Expert Committee criteria was associated with significant increased MACE risk compared with normoglycemia (adjusted hazard ratio [HR], 1.484 [95% CI, 1.139–1.935];
P
=0.0035). The VHR group was associated with increased MACE risk compared with the non‐VHR group (adjusted HR, 1.783 [95% CI, 1.344–2.366],
P
<0.0001). The VHR criteria played an important role in risk stratification, and prediabetes combined with VHR criteria was associated with higher MACE risk regardless of the prediabetes definition.

Conclusions
Our findings suggested the potential use of the World Health Organization/International Expert Committee definition and VHR criteria in risk stratification of patients with prediabetes and stable coronary heart disease.
Clinical Characteristics and Outcomes of Patients With Heart Failure With Preserved Ejection Fraction and With Reduced Ejection Fraction According to the Prognostic Nutritional Index: Findings From PARADIGM‐HF and PARAGON‐HF
Authors: Solano Simone , Yang Mingming , Tolomeo Paolo , Kondo Toru , Shen Li , Jhund Pardeep S. , Anand Inder S. , Desai Akshay S. , Lam Carolyn S. P. , Maggioni Aldo P. , Martinez Felipe A. , Rouleau Jean L. , Vaduganathan Muthiah , van Veldhuisen Dirk J. , Zannad Faiez , Zile Michael R. , Packer Milton , Solomon Scott D. , McMurray John J. V. 
Published: December 2024

Background
The importance of nutritional status is underappreciated in patients with heart failure (HF). This study aimed to describe the range of the prognostic nutrition index (PNI), and the clinical characteristics and outcomes according to PNI, in patients with HF with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF). The primary outcome was the composite of HF hospitalization or cardiovascular death.

Methods and Results
Individual patient data from the PARAGON‐HF (Prospective Comparison of ARNI [Angiotensin Receptor–Neprilysin Inhibitor] with ARB [Angiotensin Receptor Blocker] Global Outcomes in HFpEF) and PARADIGM‐HF (Prospective Comparison of ARNI With ACEI [Angiotensin‐Converting Enzyme Inhibitor] to Determine Impact on Global Mortality and Morbidity in HF) trials were used to examine patient characteristics and outcomes according to quartiles of PNI. Cox regression was used to analyze clinical outcomes, and multivariable fractional polynomial interaction analysis to examine the effects of sacubitril‐valsartan, according to PNI. Patients with lower PNI (poorer nutrition) were older, frailer, and had more comorbidities and worse HF status, with greater congestion. Patients with lower PNI had biomarker abnormalities indicating inflammation, bone marrow suppression, and increased collagen turnover, among other physiologic perturbations. Lower PNI was associated with worse outcomes; that is, the rate of the primary end point among patients in the first quartile was 11.31 (10.20–12.54) compared with 7.09 (6.17–8.14) per 100 person‐years in the fourth quartile. These associations persisted after adjustment for other prognostic variables. PNI did not modify the effects of sacubitril‐valsartan in HFrEF although sacubitril/valsartan seemed to have a greater benefit in patients with HFpEF with a higher PNI.

Conclusions
Nutritional status, assessed using PNI, is an independent predictor of poor outcomes in HF. Evaluation of nutritional status in clinical practice, the causes of undernutrition, and whether undernutrition should be a therapeutic target, are all worthy of further investigation in HF.
Transient Receptor Potential Vanilloid 4 Calcium‐Permeable Channel Contributes to Valve Stiffening in Aortic Stenosis
Authors: Dutta Bidisha , Rahaman Suneha G. , Mukherjee Pritha , Rahaman Shaik O. 
Published: December 2024

Background
Aortic valve stenosis (AVS) is a progressive disease characterized by fibrosis, inflammation, calcification, and stiffening of the aortic valve leaflets, leading to disrupted blood flow. If untreated, AVS can progress to heart failure and death within 2 to 5 years. Uncovering the molecular mechanisms behind AVS is key for developing effective noninvasive therapies. Emerging evidence highlights that matrix stiffness affect gene expression, inflammation, and cell differentiation. Activation of valvular interstitial cells into myofibroblasts, along with excessive extracellular matrix accumulation and remodeling, are major contributors to AVS progression. Inflammation further exacerbates the disease, as macrophages infiltrate valve leaflets, enhancing inflammation, activating valvular interstitial cells, and driving extracellular matrix remodeling. Our lab and others have shown that the activities of macrophages and fibroblasts are sensitive to matrix stiffness. Previously, we identified mechanosensitive transient receptor potential vanilloid 4 (TRPV4) channels as key regulators of fibrosis and macrophage activation, implicating TRPV4 in AVS as a potential stiffness sensor.

Methods and Results
Herein, we found elevated levels of TRPV4, α‐smooth muscle actin, and cluster of differentiation 68 proteins in human AVS tissues compared with controls. Furthermore, the stiffening of human aortic valve tissue is associated with the levels of myofibroblasts, macrophages, and TRPV4 protein expression. In a mouse model, TRPV4 promoted valve stiffening during hypercholesterolemia‐induced AVS. Additionally, TRPV4 mediated intracellular stiffness in valvular interstitial cells in response to transforming growth factor β1, which was blocked by the TRPV4 antagonist GSK2193874.

Conclusions
These findings reveal a novel mechanism linking TRPV4 to valve stiffening, providing insights into how extracellular matrix mechanical properties drive inflammation and fibrosis in AVS.
Days at Home After Transcatheter Mitral Valve Repair Versus Medical Therapy Alone in Heart Failure
Authors: Chung Mabel , Almarzooq Zaid I. , Tale Archana , Song Yang , Dahabreh Issa J. , Kazi Dhruv S. , Baron Suzanne J. , Yeh Robert W. 
Published: December 2024

Background
Transcatheter edge‐to‐edge repair of the mitral valve (mTEER) reduced a hierarchical end point that included death and heart failure hospitalization in COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation Trial). However, the magnitude to which mTEER increases the number of days a patient spends at home (DAH) in the first few years after treatment, a patient‐centered end point not captured routinely in clinical trials, has not been evaluated. We compared 1‐ and 2‐year DAH among patients with functional mitral regurgitation and heart failure randomized to mTEER plus medical therapy versus medical therapy alone (control) by linking the COAPT trial to comprehensive health care claims data.

Methods and Results

We linked data from COAPT trial participants to Medicare fee‐for‐service claims. DAH was calculated as the number of days alive and spent outside a hospital, skilled nursing facility, inpatient rehabilitation, long‐term acute care hospital, emergency department, or observation stay after randomization. Treatment groups were compared using quantile regression to calculate the area under the curve of cumulative distribution functions. We linked 271 patients (mTEER 136/302, control 135/312) for a 2‐year follow‐up. Mean±SD DAH at 1 year was 312.0±95.6 in mTEER and 298.1±107.5 in controls with similar area under the curve (difference 13.9 days [−10.5 to 38.3],
P
=0.26). DAH at 2 years was 577.2±235.6 in mTEER and 518.2±253.0 in control with a higher area under the curve in mTEER (difference 59.0 days [0.07 to 117.9],
P
=0.0497).

Conclusions
In the COAPT trial linked to Medicare claims, patients randomized to mTEER spent a similar number of DAH at 1 year but more time at home at 2 years compared with medical therapy alone.
The Manifestation of Religious Beliefs by Staff of Penitentiaries and Detention Centres
Authors: Sitarz Olga , Jaworska–Wieloch Anna , Hanc Jakub 
Published: December 2024

Abstract
The article examines the expression of religious beliefs by prison staff in penitentiary units. The publication answers the following three questions: (i) how do penitentiary and detention centre staff view the possibility of the expression of their religious beliefs while at work in prison?; (ii) what is the current legal situation regarding the possibility of manifesting religious freedom by prison staff?; and (iii) what assessment is to be made, taking into account the established legal framework, with regard to discrimination and respect for equality and diversity? An analysis of international case law makes it possible to put forward an argument that prohibitions on the wearing of religious symbols by state officials and other staff members are an unjustified restriction of religious freedom, leading to discrimination on the grounds of religion. The compliance with the prohibition on discrimination cannot consist of removing or concealing differences in the manifestation of religious beliefs.