bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality and Cardiovascular End Points In Relation to the Aortic Pulse Wave Components: An Individual-Participant Meta-Analysis
Authors: Norton Gavin R. , An De-Wei , Aparicio Lucas S. , Yu Yu-Ling , Wei Fang-Fei , Niiranen Teemu J. , Liu Chen , Stolarz-Skrzypek Katarzyna , Wojciechowska Wiktoria , Jula Antti M. , Rajzer Marek , Martens Dries S. , Verhamme Peter , Li Yan , Kawecka-Jaszcz Kalina , Nawrot Tim S. , Staessen Jan A. , Woodiwiss Angela J. ,   The International Database of Central Arterial Properties for Risk Stratification Investigators
Published: February 2024

BACKGROUND:

Wave separation analysis enables individualized evaluation of the aortic pulse wave components. Previous studies focused on the pressure height with overall positive but differing results. In the present analysis, we assessed the associations of the pressure of forward and backward (P
for
and P
ref
) pulse waves with prospective cardiovascular end points, with extended analysis for time to pressure peak (T
for
and T
ref
).

METHODS:
Participants in 3 IDCARS (International Database of Central Arterial Properties for Risk Stratification) cohorts (Argentina, Belgium, and Finland) aged ≥20 years with valid pulse wave analysis and follow-up data were included. Pulse wave analysis was done using the SphygmoCor device, and pulse wave separation was done using the triangular method. The primary end points consisted of cardiovascular mortality and nonfatal cardiovascular and cerebrovascular events. Multivariable-adjusted Cox regression was used to calculate hazard ratios.

RESULTS:

A total of 2206 participants (mean age, 57.0 years; 55.0% women) were analyzed. Mean±SDs for P
for
, P
ref
, T
for
, and T
for
/T
ref
were 31.0±9.1 mm Hg, 20.8±8.4 mm Hg, 130.8±35.5, and 0.51±0.11, respectively. Over a median follow-up of 4.4 years, 146 (6.6%) participants experienced a primary end point. Every 1 SD increment in P
for
, T
for
, and T
for
/T
ref
was associated with 27% (95% CI, 1.07–1.49), 25% (95% CI, 1.07–1.45), and 32% (95% CI, 1.12–1.56) higher risk, respectively. Adding T
for
and T
for
/T
ref
to existing risk models improved model prediction (∆Uno’s C, 0.020;
P
<0.01).

CONCLUSIONS:

Pulse wave components were predictive of composite cardiovascular end points, with T
for
/T
ref
showing significant improvement in risk prediction. Pending further confirmation, the ratio of time to forward and backward pressure peak may be useful to evaluate increased afterload and signify increased cardiovascular risk.
Consensus‐Based Development of a Pediatric Echocardiography Complexity Score: Design, Rationale, and Results of a Quality Improvement Collaborative
Authors: Balasubramanian Sowmya , Yu Sunkyung , Behera Sarina K. , Bhat Aarti H. , Camarda Joseph A. , Choueiter Nadine F. , Jone Pei‐Ni , Lopez Leo , Natarajan Shobha S. , Parra David A. , Parthiban Anitha , Sachdeva Ritu , Srivastava Shubhika , Tierney Elif Seda Selamet 
Published: February 2024

Background
The complexity of congenital heart disease has been primarily stratified on the basis of surgical technical difficulty, specific diagnoses, and associated outcomes. We report on the refinement and validation of a pediatric echocardiography complexity (PEC) score.

Methods and Results
The American College of Cardiology Quality Network assembled a panel from 12 centers to refine a previously published PEC score developed in a single institution. The panel refined complexity categories and included study modifiers to account for complexity related to performance of the echocardiogram. Each center submitted data using the PEC scoring tool on 15 consecutive inpatient and outpatient echocardiograms. Univariate and multivariate analyses were performed to assess for independent predictors of longer study duration. Among the 174 echocardiograms analyzed, 68.9% had underlying congenital heart disease; 44.8% were outpatient; 34.5% were performed in an intensive care setting; 61.5% were follow‐up; 46.6% were initial or preoperative; and 9.8% were sedated. All studies had an assigned PEC score. In univariate analysis, longer study duration was associated with several patient and study variables (age <2 years, PEC 4 or 5, initial study, preoperative study, junior or trainee scanner, and need for additional imaging). In multivariable analysis, a higher PEC score of 4 or 5 was independently associated with longer study duration after controlling for study variables and center variation.

Conclusions
The PEC scoring tool is feasible and applicable in a variety of clinical settings and can be used for correlation with diagnostic errors, allocation of resources, and assessment of physician and sonographer effort in performing, interpreting, and training in pediatric echocardiography.
Genetic‐Guided Pharmacotherapy for Coronary Artery Disease: A Systematic and Critical Review of Economic Evaluations
Authors: Lim Ka Keat , Koleva‐Kolarova Rositsa , Kamaruzaman Hanin Farhana , Kamil Ahmad Amir , Chowienczyk Phil , Wolfe Charles D. A. , Fox‐Rushby Julia 
Published: February 2024

Background
Genetic‐guided pharmacotherapy (PGx) is not recommended in clinical guidelines for coronary artery disease (CAD). We aimed to examine the extent and quality of evidence from economic evaluations of PGx in CAD and to identify variables influential in changing conclusions on cost‐effectiveness.

Methods and Results
From systematic searches across 6 databases, 2 independent reviewers screened, included, and rated the methodological quality of economic evaluations of PGx testing to guide pharmacotherapy for patients with CAD. Of 35 economic evaluations included, most were model‐based cost‐utility analyses alone, or alongside cost‐effectiveness analyses of PGx testing to stratify patients into antiplatelets (25/35), statins (2/35), pain killers (1/35), or angiotensin‐converting enzyme inhibitors (1/35) to predict CAD risk (8/35) or to determine the coumadin doses (1/35). To stratify patients into antiplatelets (96/151 comparisons with complete findings of PGx versus non‐PGx), PGx was more effective and more costly than non‐PGx clopidogrel (28/43) but less costly than non‐PGx prasugrel (10/15) and less costly and less effective than non‐PGx ticagrelor (22/25). To predict CAD risk (51/151 comparisons), PGx using genetic risk scores was more effective and less costly than clinical risk score (13/17) but more costly than no risk score (16/19) or no treatment (9/9). The remaining comparisons were too few to observe any trend. Mortality risk was the most common variable (47/294) changing conclusions.

Conclusions
Economic evaluations to date found PGx to stratify patients with CAD into antiplatelets or to predict CAD risk to be cost‐effective, but findings varied based on the non‐PGx comparators, underscoring the importance of considering local practice in deciding whether to adopt PGx.
Association of Cardiac Biomarkers in Combination With Cognitive Impairment After Acute Ischemic Stroke
Authors: Yang Pinni , Wang Shuyao , Zhong Chongke , Yin Jieyun , Yang Jingyuan , Wang Aili , Xu Tan , Zhang Yonghong 
Published: February 2024

Background
Poststroke cognitive impairment is a severe and common clinical complication that constitutes a substantial global health burden. We aimed to evaluate the association of 3 cardiac biomarkers in combination with poststroke cognitive impairment and their prognostic significance.

Methods and Results

This prospective study included 566 patients with ischemic stroke. Cardiac biomarkers, including sST2 (soluble suppression of tumorigenicity‐2 receptor), GDF‐15 (growth differentiation factor‐15), and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide), were measured. Cognitive impairment was defined as a Mini‐Mental State Examination score of <27 or a Montreal Cognitive Assessment score of <25 at 3 months after ischemic stroke. Odds of cognitive impairment 3 months after ischemic stroke increased with the number of elevated cardiac biomarkers (sST2, GDF‐15, and NT‐proBNP;
P
trend
<0.001). The multivariable adjusted odds ratios (95% CIs) of cognitive impairment defined by the Mini‐Mental State Examination and Montreal Cognitive Assessment were 2.45 (1.48–4.07) and 1.86 (1.10–3.14) for the participants with ≥2 elevated cardiac biomarkers, respectively, compared with those without any elevated cardiac biomarker. Additionally, higher cardiac biomarker scores were associated with an increased risk of cognitive impairment (
P
trend
<0.05). Simultaneously adding all 3 cardiac biomarkers to the basic model with traditional risk factors significantly improved the risk prediction of Mini‐Mental State Examination‐defined cognitive impairment (net reclassification improvement=34.99%,
P
<0.001; integrated discrimination index=2.67%,
P
<0.001). Similar findings were observed using the Montreal Cognitive Assessment scores.

Conclusions
An increased number of elevated novel cardiac biomarkers were associated with an increased odds of poststroke cognitive impairment, suggesting that a combination of these cardiac biomarkers may improve the risk prediction of cognitive impairment.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01840072.
Liver X Receptor Agonist 4β‐Hydroxycholesterol as a Prognostic Factor in Coronary Artery Disease
Authors: Rahunen Roosa , Tulppo Mikko , Rinne Valtteri , Lepojärvi Samuli , Perkiömäki Juha S. , Huikuri Heikki V. , Ukkola Olavi , Junttila Juhani , Hukkanen Janne 
Published: February 2024

Background
Regardless of progress in treatment of coronary artery disease (CAD), there is still a significant residual risk of death in patients with CAD, highlighting the need for additional risk stratification markers. Our previous study provided evidence for a novel blood pressure–regulating mechanism involving 4β‐hydroxycholesterol (4βHC), an agonist for liver X receptors, as a hypotensive factor. The aim was to determine the role of 4βHC as a prognostic factor in CAD.

Methods and Results

The ARTEMIS (Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection) cohort consists of 1946 patients with CAD. Men and women were analyzed separately in quartiles according to plasma 4βHC. Basic characteristics, medications, ECG, and echocardiography parameters as well as mortality rate were analyzed. At baseline, subjects with a beneficial cardiovascular profile, as assessed with traditional markers such as body mass index, exercise capacity, prevalence of diabetes, and use of antihypertensives, had the highest plasma 4βHC concentrations. However, in men, high plasma 4βHC was associated with all‐cause death, cardiac death, and especially sudden cardiac death (SCD) in a median follow‐up of 8.8 years. Univariate and comprehensively adjusted hazard ratios for SCD in the highest quartile were 3.76 (95% CI, 1.6–8.7;
P
=0.002) and 4.18 (95% CI, 1.5–11.4;
P
=0.005), respectively. In contrast, the association of cardiac death and SCD in women showed the lowest risk in the highest 4βHC quartile.

Conclusions
High plasma 4βHC concentration was associated with death and especially SCD in men, while an inverse association was detected in women. Our results suggest 4βHC as a novel sex‐specific risk marker of cardiac death and especially SCD in chronic CAD.

Registration Information

clinicaltrials.gov
. Identifier NCT01426685.
Cost Effectiveness of Dapagliflozin for Heart Failure Across the Spectrum of Ejection Fraction: An Economic Evaluation Based on Pooled, Individual Participant Data From the DELIVER and DAPA‐HF Trials
Authors: Bhatt Ankeet S. , Vaduganathan Muthiah , Claggett Brian L. , Kulac Ian J. , Anand Inder S. , Desai Akshay S. , Fang James C. , Hernandez Adrian F. , Jhund Pardeep S. , Kosiborod Mikhail N. , Sabatine Marc S. , Shah Sanjiv J. , Vardeny Orly , McMurray John J. V. , Solomon Scott D. , Gaziano Thomas A. 
Published: February 2024

Background
The sodium glucose cotransporter‐2 inhibitors are guideline‐recommended to treat heart failure across the spectrum of left ventricular ejection fraction; however, economic evaluations of adding sodium glucose cotransporter‐2 inhibitors to standard of care in chronic heart failure across a broad left ventricular ejection fraction range are lacking.

Methods and Results
We conducted a US‐based cost‐effectiveness analysis of dapagliflozin added to standard of care in a chronic heart failure population using pooled, participant data from the DAPA‐HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trials. The 3‐state Markov model used estimates of transitional probabilities, effectiveness of dapagliflozin, and utilities from the pooled trials. Costs estimates were obtained from published sources, including published rebates in dapagliflozin cost. Adding dapagliflozin to standard of care was estimated to produce an additional 0.53 quality‐adjusted life years (QALYs) compared with standard of care alone. Incremental cost effectiveness ratios were $85 554/QALY when using the publicly reported full (undiscounted) Medicare cost ($515/month) and $40 081/QALY, at a published nearly 50% rebate ($263/month). The addition of dapagliflozin to standard of care would be of at least intermediate value (<$150 000/QALY) at a cost of <$872.58/month, of high value (<$50 000/QALY) at <$317.66/month, and cost saving at <$40.25/month. Dapagliflozin was of at least intermediate value in 92% of simulations when using the full (undiscounted) Medicare list cost in probabilistic sensitivity analyses. Cost effectiveness was most sensitive to the dapagliflozin cost and the effect on cardiovascular death.

Conclusions
The addition of dapagliflozin to standard of care in patients with heart failure across the spectrum of ejection fraction was at least of intermediate value at the undiscounted Medicare cost and may be potentially of higher value on the basis of the level of discount, rebates, and price negotiations offered.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifiers: NCT01035255 & NCT01920711.
Decoding the Cell Atlas and Inflammatory Features of Human Intracranial Aneurysm Wall by Single‐Cell RNA Sequencing
Authors: Ji Hang , Li Yue , Sun Haogeng , Chen Ruiqi , Zhou Ran , Yang Yongbo , Wang Rong , You Chao , Xiao Anqi , Yi Liu 
Published: February 2024

Background
Intracranial aneurysm (IA) is common and occasionally results in life‐threatening hemorrhagic strokes. However, the cell architecture and inflammation in the IA dome remain less understood.

Methods and Results

Single‐cell RNA sequencing was performed on ruptured and unruptured human IA domes for delineating the cell atlas, gene expression perturbations, and inflammation features. Two external bulk mRNA sequencing–based data sets and serological results of 126 patients were collected for validation. As a result, a total of 21 332 qualified cells were captured. Vascular cells, including endothelial cells, smooth muscle cells, fibroblasts, and pericytes, were assigned in extremely sparse numbers (4.84%), and were confirmed by immunofluorescence staining. Pericytes, characterized by
ABCC9
and
HIGD1B
, were identified in the IA dome for the first time. Abundant immune cells were identified, with the proportion of monocytes/macrophages and neutrophils being remarkably higher in ruptured IA. The lymphocyte compartment was also thoroughly categorized. By leveraging external data sets and machine learning algorithms, macrophages were robustly associated with IA rupture, irrespective of their polarization status. The single nucleotide polymorphism rs2280543, which is identified in East Asian populations, was associated with macrophage metabolic reprogramming through regulating
TALDO1
expression.

Conclusions
This study provides insights into the cellular architecture and inflammatory features in the IA dome and may enlighten novel therapeutics for unruptured IA.
Severity and Remission of Metabolic Dysfunction–Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence
Authors: Gao Jingli , Li Yuhao , Zhang Yijun , Zhan Xin , Tian Xue , Li Junjuan , Wang Ru , He Yan , Wang Anxin , Wu Shouling 
Published: February 2024

Background
The association of the severity of hepatic steatosis in metabolic dysfunction–associated fatty liver disease (MAFLD)/metabolic dysfunction–associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear.

Methods and Results

The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m
2
or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow‐up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non‐MAFLD (HR, 1.12 [95% CI, 1.09–1.16]), and this risk increased with increasing severity of hepatic steatosis (
P
‐trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non‐MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95–1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non‐MASLD (HR, 1.15 [95% CI, 1.03–1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild‐MAFLD/MASLD remission compared with persistent non‐MAFLD/MASLD, but moderated/severe‐MAFLD/MASLD remission still had a higher risk.

Conclusions
The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.
Discrimination, Smoking, and Cardiovascular Disease Risk: A Moderated Mediation Analysis With MESA
Authors: Cook Stephanie H. , Wood Erica P. , Stein James H. , McClelland Robyn L. 
Published: February 2024

Background
Carotid intima‐media thickness (cIMT) and carotid plaque are reliable indicators of cardiovascular disease risk, and research highlights that racial and ethnic minority individuals generally exhibit higher cIMT and carotid plaque than White individuals. At present, the mechanisms driving these disparities among different racial and ethnic and biological sex groups are poorly understood.

Methods and Results
Data came from the baseline examination of MESA (Multi‐Ethnic Study of Atherosclerosis). A total of 6814 participants aged 45 to 84 years free of clinical cardiovascular disease completed assessments on health behavior and perceived discrimination. Four sex‐stratified moderated mediation models examined associations between discrimination, cigarette smoking, and mean cIMT and plaque. We hypothesized that cigarette use would mediate the association between discrimination and carotid artery disease features, and that these would differ by race and ethnicity. Indirect effects of discrimination on plaque were observed among Hispanic women such that discrimination was associated with cigarette use and, in turn, higher plaque (β=0.04 [95% CI, 0.01–0.08]). Indirect effects of discrimination on mean cIMT were found among Hispanic (β=0.003 [95% CI, 0.0001–0.007]) and White men (β=0.04 [95% CI, 0.01–0.08]) such that discrimination was associated with cigarette use and, in turn, higher cIMT. Finally, a positive indirect effect of discrimination on plaque was observed among Hispanic men (β=0.03 [95% CI, 0.004–0.07]). No other racial and ethnic differences were observed.

Conclusions
To understand and address social determinants of cardiovascular disease, researchers must incorporate an intersectional framework that will allow us to understand the complex nature of discrimination and cardiovascular disease risk for individuals of varying intersecting identities and social positions.
Echocardiographic Profiling Predicts Clinical Outcomes After Mitral Transcatheter Edge‐to‐Edge Repair
Authors: Hatab Taha , Samimi Sahar , Bou Chaaya Rody G. , Qamar Fatima , Kharsa Chloe , Wessly Priscilla , Faza Nadeen , Little Stephen H. , Atkins Marvin D. , Reardon Michael J. , Kleiman Neal S. , Zoghbi William A. , Nagueh Sherif F. , Zaid Syed , Goel Sachin S. 
Published: February 2024

Background
Prior studies investigating the impact of residual mitral regurgitation (MR), tricuspid regurgitation (TR), and elevated predischarge transmitral mean pressure gradient (TMPG) on outcomes after mitral transcatheter edge‐to‐edge repair (TEER) have assessed each parameter in isolation. We sought to examine the prognostic value of combining predischarge MR, TR, and TMPG to study long‐term outcomes after TEER.

Methods and Results

We reviewed the records of 291 patients who underwent successful mitral TEER at our institution between March 2014 and June 2022. Using well‐established outcomes‐related cutoffs for predischarge MR (≥moderate), TR (≥moderate), and TMPG (≥5 mm Hg), 3 echo profiles were developed based on the number of risk factors present (optimal: 0 risk factors, mixed: 1 risk factor, poor: ≥2 risk factors). Discrimination of the profiles for predicting the primary composite end point of all‐cause mortality and heart failure hospitalization at 2 years was examined using Cox regression. Overall, mean age was 76.7±10.6 years, 43.3% were women, and 53% had primary MR. Two‐year event‐free survival was 61%. Predischarge TR≥moderate, MR≥moderate, and TMPG≥5 mm Hg were risk factors associated with the primary end point. Compared with the optimal profile, there was an incremental risk in 2‐year event‐rate with each worsening profile (optimal as reference; mixed profile: hazard ratio (HR), 2.87 [95% CI, 1.71–5.17],
P
<0.001; poor profile: HR, 3.76 [95% CI, 1.84–6.53],
P
<0.001). Echocardiographic profile was statistically associated with the 2‐year mortality end point (optimal as reference; mixed profile: HR, 3.55 [95% CI, 1.81–5.96],
P
<0.001; poor profile: HR, 3.39 [95% CI, 2.56–7.33],
P
=0.02).

Conclusions
The echocardiographic profile integrating predischarge TR, MR, and TMPG presents a novel prognostic stratification tool for patients undergoing mitral TEER.