bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hispanic/Latino Ethnicity Is an Independent Predictor of Worse Survival for Gastric Cancer in a Multicenter Safety-Net Patient Population
Authors: Klingbeil Kyle D. , Dillon Dustin L. , Zarrinkhoo Erfan , Bechay Kirollos , Park Joon Y. , Rook Jordan M. , Mederos Michael A. , Girgis Mark D. , Chen Keren , Chen Kuan-Ting , Bastani Roshan , Manouchehr-Pour Shawdi , Dubé Priyanka , Viragh Karoly , Thomas Mariam , Chiu Victor , Kadera Brian E. 
Published: August 2024

Abstract

Background:
Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients.

Methods:
We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016, and December 31, 2020, within Los Angeles County’s safety-net hospital system. Gastric cancer–specific survival was compared between the two cohorts using the Kaplan–Meier estimate and Cox proportional-hazards regression model.

Results:
In total, 448 patients who received care from five medical centers were included; 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34–2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs. 60.7 years, P &lt; 0.01), demonstrate higher state area deprivation index (6.4 vs. 5.0, P &lt; 0.01), and present with metastatic disease (59.8% vs. 45%, P = 0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival [HR 1.56, (95% CI, 1.06–2.28); P = 0.02].

Conclusions:
Hispanic patients treated within a large, multicenter safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors.

Impact:
Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care.
See related In the Spotlight, p. 12
Antisense Oligonucleotide Therapy for Calmodulinopathy
Authors: Bortolin Raul H. , Nawar Farina , Park Chaehyoung , Trembley Michael A. , Prondzynski Maksymilian , Sweat Mason E. , Wang Peizhe , Chen Jiehui , Lu Fujian , Liou Carter , Berkson Paul , Keating Erin M. , Yoshinaga Daisuke , Pavlaki Nikoleta , Samenuk Thomas , Cavazzoni Cecilia B. , Sage Peter T. , Ma Qing , Whitehill Robert D. , Abrams Dominic J. , Carreon Chrystalle Katte , Putra Juan , Alexandrescu Sanda , Guo Shuai , Tsai Wen-Chin , Rubart Michael , Kubli Dieter A. , Mullick Adam E. , Bezzerides Vassilios J. , Pu William T. 
Published: August 2024

BACKGROUND:

Calmodulinopathies are rare inherited arrhythmia syndromes caused by dominant heterozygous variants in
CALM1
,
CALM2
, or
CALM3
, which each encode the identical CaM (calmodulin) protein. We hypothesized that antisense oligonucleotide (ASO)–mediated depletion of an affected calmodulin gene would ameliorate disease manifestations, whereas the other 2 calmodulin genes would preserve CaM level and function.

METHODS:

We tested this hypothesis using human induced pluripotent stem cell–derived cardiomyocyte and mouse models of
CALM1
pathogenic variants.

RESULTS:

Human
CALM1

F142L/+

induced pluripotent stem cell–derived cardiomyocytes exhibited prolonged action potentials, modeling congenital long QT syndrome. CALM1 knockout or CALM1-depleting ASOs did not alter CaM protein level and normalized repolarization duration of
CALM1

F142L/+

induced pluripotent stem cell–derived cardiomyocytes. Similarly, an ASO targeting murine
Calm1
depleted
Calm1
transcript without affecting CaM protein level. This ASO alleviated drug-induced bidirectional ventricular tachycardia in
Calm1

N98S/+

mice without a deleterious effect on cardiac electrical or contractile function.

CONCLUSIONS:
These results provide proof of concept that ASOs targeting individual calmodulin genes are potentially effective and safe therapies for calmodulinopathies.
Hypoperfusion Intensity Ratio as an Indirect Imaging Surrogate in Patients With Anterior Circulation Large‐Vessel Occlusion and Association of Baseline Characteristics With Poor Collateral Status
Authors: Hamam Omar , Gudenkauf Julie , Moustafa Rawan , Cho Andrew , Montes Daniel , Sharara Muhannad , Moustafa Abdallah , Radmard Mahla , Nabi Mehreen , Chen Kevin , Sepehri Sadra , Shin Christopher , Mazumdar Ishan , Kim Minsoo , Mohseni Alireza , Malhotra Ajay , Romero Javier , Yedavalli Vivek 
Published: August 2024

Background
Collateral status (CS) plays a crucial role in infarct growth rate, risk of postthrombectomy hemorrhage, and overall clinical outcomes in patients with acute ischemic stroke (AIS) secondary to anterior circulation large‐vessel occlusions (LVOs). Hypoperfusion intensity ratio has been previously validated as an indirect noninvasive pretreatment imaging biomarker of CS. In addition to imaging, derangements in admission laboratory findings can also influence outcomes in patients with AIS‐LVO. Therefore, our study aims to assess the relationship between admission laboratory findings, baseline characteristics, and CS, as assessed by hypoperfusion intensity ratio in patients with AIS‐LVO.

Methods and Results

In this retrospective study, consecutive patients presenting with AIS secondary to anterior circulation LVO who underwent pretreatment computed tomography perfusion were included. The computed tomography perfusion data processed by RAPID (Ischema View, Menlo Park, CA) generated the hypoperfusion intensity ratio. Binary logistic regression models were used to assess the relationship between patients' baseline characteristics, admission laboratory findings, and poor CS. A total of 221 consecutive patients with AIS‐LVO between January 2017 and September 2022 were included in our study (mean±SD age, 67.0±15.8 years; 119 men [53.8%]). Multivariable logistic regression showed that patients with AIS caused by cardioembolic and cryptogenic causes (adjusted odds ratio [OR], 2.67; 95% CI, 1.20–5.97;
P
=0.016), those who presented with admission National Institutes of Health Stroke Scale score ≥12 (adjusted OR, 3.12; 95% CI, 1.61–6.04;
P
=0.001), and male patients (adjusted OR, 2.06; 95% CI, 1.13–3.77;
P
=0.018) were associated with poor CS.

Conclusions
Stroke caused by cardioembolic or cryptogenic causes, admission National Institutes of Health Stroke Scale score of ≥12, and male sex were associated with poor CS, as defined by hypoperfusion intensity ratio in the patients with AIS‐LVO.
Natural Course of Electrocardiographic Features in Arrhythmogenic Right Ventricular Cardiomyopathy and Their Relation to Ventricular Arrhythmic Events
Authors: Svensson Anneli , Jensen Henrik Kjaerulf , Boonstra Machteld J. , Tétreault‐Langlois Marianne , Dahlberg Pia , Bundgaard Henning , Christensen Alex Hørby , Rylance Rebecca T. , Svendsen Jesper H. , Cadrin‐Tourigny Julia , te Riele Anneline S. J. M. , Platonov Pyotr G. 
Published: August 2024

Background
Electrocardiographic abnormalities are common in arrhythmogenic right ventricular cardiomyopathy and are included in the 2010 Task Force Criteria. Their time course, however, remains uncertain. In this retrospective observational study, we aimed to assess the long‐term evolution of electrocardiographic characteristics and their relation to ventricular arrhythmias.

Methods and Results

Three hundred fifty‐three patients with arrhythmogenic right ventricular cardiomyopathy as per the 2010 Task Force Criteria with 6871 automatically processed 12‐lead digital ECGs were included. The relationship between the electrocardiographic parameters and the risk of ventricular arrhythmias was assessed at 10 years from the first ECG. Electrocardiographic parameters were compared between the first contact ECG, the ECG at diagnosis, and the most recent ECG. Median time between the first and the latest ECG was 6 [interquartile range, 1–14] years. Reductions of QRS voltage, R‐ and T‐wave amplitudes between the first, diagnostic, and the latest ECGs were observed across precordial and extremity leads. Mean QRS duration increased from 96 to 102 ms (
P
<0.001), terminal activation duration (V
1
) from 47 to 52 ms (
P
<0.001), and QTc from 419 to 432 ms (
P
<0.001). T‐wave inversions in leads V
3
to V
6
and aVF at first ECG were associated with ventricular arrhythmias (adjusted hazard ratio [HR
adj
][V
3
], 2.03 [95% CI, 1.23–3.34] and HR
adj
[aVF], 1.87 [95% CI, 1.13–3.08]).

Conclusions

Depolarization and repolarization parameters evolved over time in patients with arrhythmogenic right ventricular cardiomyopathy, supporting the progressive nature of arrhythmogenic right ventricular cardiomyopathy. Electrocardiographic abnormalities may be detected before diagnosis and might, although not fulfilling the 2010 Task Force Criteria, be markers of early disease. T‐wave inversion in leads V
3
or aVF before diagnosis was associated with ventricular arrhythmias during follow‐up.
Lipids, Apolipoproteins, Lipid‐Lowering Drugs, and the Risk of Cerebral Small Vessel Disease: A Mendelian Randomization Study
Authors: Xie Yi , Liu Shuai , Wang Xinyue , Huang Hao , Wang Minghuan , Qu Wensheng , Yu Zhiyuan , Wang Wei , Luo Xiang 
Published: August 2024

Background
Serum lipids are causally involved in the occurrence of atherosclerosis, but their roles in cerebral small vessel disease remain unclear. This study aimed to investigate the causal roles of lipid or apolipoprotein traits in cerebral small vessel disease and to determine the effects of lipid‐lowering interventions on this disease.

Methods and Results

Data on genetic instruments of lipids/apolipoproteins, as well as characteristic cerebral small vessel disease manifestations, including small vessel stroke (SVS) and white matter hyperintensity (WMH), were obtained from publicly genome‐wide association studies. Through 2‐sample Mendelian randomization analyses, it was found that decreased levels of high‐density lipoprotein cholesterol (odds ratio [OR], 0.85,
P
=0.007) and apolipoprotein A‐I (OR, 0.83,
P
=0.005), as well as increased level of triglycerides (OR, 1.16,
P
=0.025) were associated with a higher risk of SVS. A low level of high‐density lipoprotein cholesterol (OR, 0.93,
P
=0.032) was associated with larger WMH volume. Specifically, the genetically determined expressions of lipid fractions in various size‐defined lipoprotein particles were more closely related to the risk of SVS than WMH. Moreover, it was found that the hypertension trait ranked at the top in mediating the causal effect of hyperlipidemia on SVS and WMH by using Mendelian randomization‐based mediation analysis. For drug‐target Mendelian randomization, the low‐density lipoprotein cholesterol‐reducing genetic variation alleles at
HMGCR
and
NL1CL1
genes and the high‐density lipoprotein cholesterol‐raising genetic variation alleles at the
CETP
gene were predicted to decrease the risk of SVS.

Conclusions
The present Mendelian randomization study indicates that genetically determined hyperlipidemia is closely associated with a higher risk of cerebral small vessel disease, especially SVS. Lipid‐lowering drugs could be potentially considered for the therapies and preventions of SVS rather than WMH.
Predictors and Long‐Term Clinical Impact of Heart Failure With Improved Ejection Fraction After Acute Myocardial Infarction
Authors: Kim Kyung An , Kim Sang Hyun , Lee Kwan Yong , Yoon Andrew H. , Hwang Byung‐Hee , Choo Eun Ho , Kim Jin Jin , Choi Ik Jun , Kim Chan Joon , Lim Sungmin , Park Mahn‐Won , Yoo Ki‐Dong , Jeon Doo Soo , Ahn Youngkeun , Jeong Myung Ho , Chang Kiyuk 
Published: August 2024

Background
Little is known about the characteristics and long‐term clinical outcomes of patients with heart failure with improved ejection fraction (HFimpEF) after acute myocardial infarction.

Methods and Results

From a multicenter, consecutive cohort of patients with acute myocardial infarction undergoing percutaneous coronary intervention, patients with an initial echocardiogram with left ventricular ejection fraction ≤40% and at least 1 follow‐up echocardiogram after 14 days and within 2 years of the initial event were considered for analyses. HFimpEF was defined as an initial left ventricular ejection fraction ≤40% and serial left ventricular ejection fraction >40% with an increase of ≥10% from baseline at follow‐up. Independent factors predicting HFimpEF were identified, and clinical outcomes of patients with HFimpEF were compared with those without improvement. From an initial cohort of 10 719 patients with acute myocardial infarction, 191 patients with HFimpEF and 256 patients with non‐HFimpEF who had initial and follow‐up echocardiographic data were analyzed. The median follow‐up duration was 4.5 (interquartile range, 2.9–5.0) years. The factors predicting HFimpEF were lower peak creatine kinase myocardial band, smaller left ventricular dimensions, lower ratio between early mitral inflow velocity and mitral annular early diastolic velocity ′, and the use of β blockers or renin–angiotensin system blockers at discharge. HFimpEF was associated with a significantly decreased risk of all‐cause death compared with non‐HFimpEF (hazard ratio, 0.377 [95% CI, 0.234–0.609];
P
<0.001). In 2‐year landmark analysis, these findings were consistent not only before but also after the landmark point. Similar findings were true for cardiovascular death and admission for heart failure.

Conclusions
Patients with HFimpEF after acute myocardial infarction showed distinct clinical and echocardiographic characteristics and were associated with better long‐term clinical outcomes.

Registration

URL:
https://www.clinicaltrials.gov
; Unique Identifier: NCT02806102.
Economic Benefits of Surgical Aortic Valve Replacement on Patients With Symptomatic Aortic Valve Regurgitation
Authors: Still Sasha Anne , Ryan Michael , Gunnarsson Candace , Heidrich Natalie , Davies James E. 
Published: August 2024

Background
Aortic regurgitation is distinguished by the backflow of blood from the aorta into the left ventricle. American College of Cardiology/American Heart Association guidelines recommend surgical aortic valve replacement (SAVR) for patients with symptomatic aortic regurgitation (sAR). This study estimates the difference in mortality, health care use, and costs between patients with sAR who receive SAVR within 12 months of diagnosis versus those who do not.

Methods and Results
We used the Optum United Healthcare database to identify 132 317 patients diagnosed with sAR from 2016 to 2021 who had at least 6 months of enrollment before sAR and 12 months of enrollment after. Criteria were no history of aortic stenosis or transcatheter aortic valve replacement and ≥2 visits for heart failure, angina, dyspnea, or syncope. Outcomes were all‐cause mortality, health care use, and annualized cost. Baseline differences in demographics and comorbidities were adjusted with inverse propensity score weighting. We modeled survival and estimated health care use and costs using Cox proportional hazards and general linear models, respectively. Of the 132 317 patients, 400 underwent SAVR within 12 months of diagnosis. They were on average younger, more often men, and with a slightly higher Elixhauser Comorbidity Index score. After inverse propensity score weighting, patients with sAR who had SAVR had lower mortality, fewer inpatient and emergency department visits, fewer hospital days, and lower annualized cost.

Conclusions
SAVR performed within 12 months of an sAR diagnosis is associated with improved mortality and lower annualized health care use and costs. These clinical and economic benefits should be considered when managing patients with sAR.
Electrophysiological Mechanism of Catestatin Antiarrhythmia: Enhancement of
I
to
,
I
K,
and
I
K1
and Inhibition of
I
Ca
‐L
in Rat Ventricular Myocytes
Authors: Zhang Ying , Chen Hua , Ma Qingmin , Jia Hui , Ma Hongyu , Du Zishuo , Liu Yan , Zhang Xiangjian , Zhang Yi , Guan Yue , Ma Huijie 
Published: August 2024

Background
Cardiovascular disease remains one of the leading causes of death globally. Myocardial ischemia and infarction, in particular, frequently cause disturbances in cardiac electrical activity that can trigger ventricular arrhythmias. We aimed to investigate whether catestatin, an endogenous catecholamine‐inhibiting peptide, ameliorates myocardial ischemia‐induced ventricular arrhythmias in rats and the underlying ionic mechanisms.

Methods and Results

Adult male Sprague‐Dawley rats were randomly divided into control and catestatin groups. Ventricular arrhythmias were induced by ligation of the left anterior descending coronary artery and electrical stimulation. Action potential, transient outward potassium current, delayed rectifier potassium current, inward rectifying potassium current, and L‐type calcium current (
I
Ca‐L
) of rat ventricular myocytes were recorded using a patch‐clamp technique. Catestatin notably reduced ventricular arrhythmia caused by myocardial ischemia/reperfusion and electrical stimulation of rats. In ventricular myocytes, catestatin markedly shortened the action potential duration of ventricular myocytes, which was counteracted by potassium channel antagonists TEACl and 4‐AP, and
I
Ca‐L
current channel agonist Bay K8644. In addition, catestatin significantly increased transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current density in a concentration‐dependent manner. Catestatin accelerated the activation and decelerated the inactivation of the transient outward potassium current channel. Furthermore, catestatin decreased
I
Ca‐L
current density in a concentration‐dependent manner. Catestatin also accelerated the inactivation of the
I
Ca‐L
channel and slowed down the recovery of
I
Ca‐L
from inactivation.

Conclusions

Catestatin enhances the activity of transient outward potassium current, delayed rectifier potassium current, and inward rectifying potassium current, while suppressing the
I
Ca‐L
in ventricular myocytes, leading to shortened action potential duration and ultimately reducing the ventricular arrhythmia in rats.
Impact of the Aortomitral Positional Anatomy on Atrioventricular Conduction Disorder Following Mitral Valve Surgery
Authors: Handa Kazuma , Kawamura Masashi , Yoshioka Daisuke , Saito Shunsuke , Kawamura Takuji , Kawamura Ai , Misumi Yusuke , Taira Masaki , Shimamura Kazuo , Komukai Sho , Kitamura Tetsuhisa , Miyagawa Shigeru 
Published: August 2024

Background
Variations in the aortomitral positional anatomy, including aortic root rotation appear to be related to variations in the location of the conduction system, including the bundle of His. However, little is known about their clinical significance.

Methods and Results

This study included 147 patients with normal ECGs who underwent mitral valve surgery. The aortomitral anatomy was classified using preoperative 3‐dimensional transesophageal echocardiography, and postoperative conduction disorders, including atrioventricular block and bundle branch block, were analyzed. Variations classified as aortomitral appearance were designated as having a center appearance (85.7%, n=126/147) or lateral appearance (14.3%, n=21/147) on the basis of whether the aortic root was located at the center or was shifted to the left fibrous trigone side. Subsequently, those with a center appearance, aortic root rotation was classified as having a center rotation (83.3% [n=105/126]), in which the commissure of the left and noncoronary aortic leaflet was located at the center, lateral rotation (14.3% [n=18/126]), rotated to the left trigone side, or medial rotation (2.4% [n=3/126]), rotated to the right. The incidence of 3‐month persistent new‐onset conduction disorder was higher in the lateral appearance than the center appearance group (21.1% versus 5.0%;
P
=0.031) and higher in the lateral rotation than in the center or medial rotation groups (29.4% versus 1.0% versus 0.0%, respectively;
P
<0.001).

Conclusions
Aortomitral variations can be classified using 3‐dimensional transesophageal echocardiography. Lateral appearance and lateral rotation are risk factors for conduction disorders in mitral valve surgery.
Rationale and Design of the Australasian Registry of Screening ECGs in National Athletes Project
Authors: Orchard Jessica J. , La Gerche Andre , Puranik Rajesh , Raju Hariharan , Davis Angus J. , Eggleton Simon , Driscoll Tim , Lorimer Michelle , Doughty Robert N. , Hamilton Bruce , Drezner Jonathan A. , Orchard John W. 
Published: August 2024

Background
Cardiac screening of elite athletes is widely recommended by Australasian sporting federations, but data are not structured to be shared. Data are lacking from underrepresented groups to inform ECG interpretation guidelines. The ARENA (Australasian Registry of Screening ECGs in National Athletes) project is a retrospective and prospective, multicenter, longitudinal, observational registry of athlete cardiac screening results and outcomes. The aim is to create a repository to improve our understanding of the diagnoses and outcomes of screening.

Methods
Participating sports that conduct cardiac screening of athletes will contribute data. This includes an initial collection (retrospective data, waiver of consent) and future prospective data (opt‐out consent). Data include sex, age, sport/event, screening date, ECG findings, cardiac test results, follow‐up details, sport participation status, cardiac diagnoses, and major cardiovascular outcomes defined as sudden cardiac arrest/death, cardiac syncope or implanted cardioverter defibrillator shock, cardiac hospitalization, and arrhythmias requiring intervention. Comparisons will be made between diagnoses, outcomes, and ECG features and analyzed by sport and sex. The ARENA project was developed in collaboration with sporting bodies, team physicians, and players association representatives and endorsed by the Australasian College of Sport & Exercise Physicians and Sports Medicine Australia.

Conclusions
The ARENA project will provide a long‐term international data repository to improve our understanding of ECG interpretation, cardiac screening and diagnoses, and the prevalence of cardiovascular outcomes in screened athletes. A unique aim is to address evidence gaps in underrepresented athlete groups, specifically female athletes and Indigenous populations. Results will inform screening policies and guidelines.