bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4134747: Trends and Disparities in Mortality Due to Thoracic Aortic Aneurysm in Patients in the United States from 1999 to 2020
Authors: Goyal Aman , . Abdullah , Maheshwari Surabhi , Saeed Humza , Jain Hritvik , Ullah Irfan , Abbasi Haleema Qayyum , Changez Mah I Kan , MAHALWAR GAURANGA
Published: November 2024

Background:
Thoracic aortic aneurysms (TAA) impact approximately 6 to 10 individuals per 100,000 people, though the actual prevalence is likely higher due to frequent asymptomatic presentations, posing a challenge for early diagnosis. The rupture of these aneurysms presents a significant risk, resulting in an estimated 30,000 deaths annually in the United States alone. This emphasizes the urgent need for enhanced detection and treatment strategies. An understanding of trends in TAA mortality is imperative for assessing the efficacy of current approaches, pinpointing vulnerable populations, and ultimately, advancing treatment equity.

Methods:
This study utilized death certificates from 1999 to 2020 sourced from the CDC WONDER Database. Deaths among individuals aged 25 years and older attributed to TAA were identified using the International Classification of Diseases, Tenth Revision (ICD-10) codes I71.1 and I71.2. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and stratified based on year, gender, race/ethnicity, and urbanization status.

Results:
Between 1999 and 2020, 47,136 deaths were reported in patients with TAA. Overall, AAMR decreased from 16.2 to 8.2 per 1,000,000 population between 1999 and 2020, with a significant decline from 1999 to 2013 (APC: -5.00; 95% CI: -5.54 to -4.5), followed by a slight increase from 2013 to 2020 (APC: 0.47; 95% CI: -1.02 to 3.06). Gender-based analysis revealed that men had consistently higher AAMRs than women (men: 11.2; 95% CI: 11 to 11.3; vs. women: 9; 95% CI: 8.9 to 9.1). Moreover, we found that AAMRs were the highest among non-Hispanic African Americans (11; 95% CI: 10.7 to 11.3) followed by non-Hispanic Whites (10.3; 95% CI: 10.2 to 10.4), non-Hispanic Asian or Pacific Islanders (9.5; 95% CI: 9 to 9.9), non-Hispanic American Indian or Alaska Native (7.8; 95% CI: 6.6 to 9), and Hispanic populations (5.2; 95% CI 5 to 5.5). In addition, non-metropolitan areas had higher AAMRs than metropolitan areas (non-metropolitan areas: 11; 95% CI: 10.8 to 11.2; vs. metropolitan: 9.8; 95% CI: 9.7 to 9.9) (Figure 1).

Conclusions:
This analysis revealed a significant decline in mortality since 1999 from TAA, with a slight upward trend in recent years. However, disparities persist, with higher AAMRs observed among men, non-Hispanic African Americans, and residents of non-metropolitan areas.
Abstract 4134754: Trends and Disparities in Mortality Due to Abdominal Aortic Aneurysm: Who Is at Risk?
Authors: Goyal Aman , Saeed Humza , Maheshwari Surabhi , . Abdullah , Sohail Amir , Changez Mah I Kan , MAHALWAR GAURANGA
Published: November 2024

Background:
Screening studies have reported a prevalence of 3-8% for abdominal aortic aneurysms (AAA). Despite a positive trend of decline over the past two decades, mortality linked to AAA remains a significant public health concern. In the United States alone, AAA complications resulted in an estimated 13,640 deaths between 2018 and 2021. Thus, understanding trends and disparities in AAA mortality is crucial for evaluating the effectiveness of current approaches and identifying vulnerable populations.

Methods:
This study analyzed death certificates from 1999 to 2020 within the CDC WONDER Database. Deaths among individuals aged 25 years and older caused by AAA were identified using the International Classification of Diseases, Tenth Revision (ICD-10) codes I71.3 and I71.4. Age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and annual percent change (APC) were computed and categorized based on year, gender, race/ethnicity, and urbanization status.

Results:
Between 1999 and 2020, 195,117 deaths were reported in patients with AAA (both ruptured and non-ruptured). Overall, AAMRs for AAA significantly decreased from 69.0 deaths in 1999 to 27.9 deaths in 2020. This decline occurred in two phases: a steeper decrease from 1999 to 2014 (APC: -5.47; 95% CI: -5.68 to -5.29) followed by a further significant decrease from 2014 to 2020 (APC: -1.66; 95% CI: -2.46 to -0.57). Gender-based analysis revealed that men consistently had higher AAMRs than women (men: 65.6; 95% CI: 65.3 to 66.0; women: 24.5; 95% CI: 24.3 to 24.7). Similarly, AAMRs varied by race/ethnicity, with the highest rates observed among non-Hispanic Whites (45.6; 95% CI: 45.3 to 45.8), followed by non-Hispanic American Indian or Alaska Natives (30.3; 95% CI: 27.9 to 32.7), non-Hispanic African Americans (27.2; 95% CI: 26.7 to 27.8), non-Hispanic Asian or Pacific Islanders (20.7; 95% CI: 20.0 to 21.4), and Hispanics (17.5; 95% CI: 17.0 to 18.0). Additionally, individuals residing in non-metropolitan areas had significantly higher AAMRs than those in metropolitan areas (non-metropolitan: 50.7; 95% CI: 50.2 to 51.1; vs. metropolitan: 39.2; 95% CI: 39.0 to 39.4) (Figure 1).

Conclusions:
This analysis revealed a significant decline in mortality from AAA. However, disparities persist, with higher AAMRs observed among men, non-Hispanic Whites, and residents of non-metropolitan areas.
Abstract 4134772: Optimizing Heart Failure with Preserved Ejection Fraction Management: Quality Review of SGTL2 Inhibitor Use
Authors: Naqvi Abeeha , Boshara Andrew , Rohant Namit , Padaliya Bimal
Published: November 2024

Heart failure with preserved ejection fraction (HFpEF) remains a diagnostic challenge despite a 50% incidence of HF admissions. H2FPEF tool is a validated scoring system that estimates HFpEF probability with a sensitivity of 69% and positive predictive value of 85%. Despite clinical research interest and therapeutic advances in HFpEF, implementation of therapies remain inconsistent. Currently ACC/AHA guidelines classify sodium-glucose cotransporter 2 inhibitors (SGLT2i) use a 2A recommendation with benefits for reducing hospital admissions. We assess the utilization of current guidelines. An observational retrospective analysis was performed of patients >18 years with a left ventricular ejection fraction of >50% seen in cardiology clinic with an ICD.10 code of diastolic heart failure from January 2022 to 2024 at a large tertiary hospital. Electronic records were reviewed for patient demographics, documentation of heart failure diagnosis, medication list and echocardiogram parameters. Primary outcome was HF related hospitalization. The study screened 79 patients, 51% females and 49% males. 20.2% of the patients were on SGLT2i, a quarter of which were female. Of those on SGLT2i, 56% were on diuretics, 81% had H2FpEF score > 5, 56% had diabetes, and 19% had a HF hospitalization. SGLT2i was stopped in 1 patient due to cost. Of the (63) 79.8% of patients not on SGLT2I, 65% were on diuretics, 90% had H2FPEF score > 5, 23% had diabetes and 32% had a HF hospitalization. 43% were males, with an average age of 71 for males and 62 for females. Ten patients had documented reasons for not being on SGLT2i including CKD, dialysis, yeast infection and denied insurance coverage. Unadjusted effect measures for HF hospitalization (HR 0.59, RRR 40.9%, OR 0.496; p 0.134). As guidelines are readily investigated and updated by expert consensus groups, evaluating practice patterns is key. Unlike other cardiac medications, SGLT2is are primarily initiated by cardiologists and recognizing barriers can identify generalizability of current guidelines. Our data looked at both objective and clinical endpoints for HFPEF diagnosis. Interestingly, women were less often started on SGLT2i and coverage was not a frequent cause for not using SGLT2i. Our quality metric analysis shows a potential protective effect of HF readmission with SGLT2i use in a highly symptomatic cohort, and suggests future directives need to focus on broadening educational reach among cardiologists.
Abstract 4134777: Predictive Factors for Early Recovery from Mechanical Circulatory Support in Patients with Fulminant Myocarditis
Authors: Ueda Tomomi , Amiya Eisuke , Hatano Masaru , Ishida Junichi , Takeda Norifumi , Akazawa Hiroshi , Komuro Issei , Takeda Norihiko
Published: November 2024

Background:
Fulminant myocarditis (FM) requiring veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is fatal and has a complicated clinical course. In such FM cases, predicting which cases are likely to achieve early recovery is crucial for developing acute-phase treatment strategies. We aimed to examine the factors predicting early recovery in fatal cases of FM requiring VA-ECMO using multicenter cohort of patients with myocarditis.

Methods:
We retrospectively analysed 343 patients with FM requiring VA-ECMO between April 2012 and March 2017. The early recovery group was defined as patients who were successfully weaned off mechanical circulatory support (MCS) within 7 days from MCS deployment and discharged with favorable outcomes. We divided patients into early recovery group and non-early recovery group. Predictors of early recovery were investigated by performing a multivariate analysis, including significant variables (
p
<0.05) identified from a univariate analysis of baseline clinical parameters and meaningful variables from previous reports.

Results:
Among the eligible patients, 71 were assigned to the early recovery group, whereas 272 were assigned to the non-early recovery group. The baseline patient demographics showed the early recovery group was significantly younger (45 [30-63] years vs. 56.5 [40-67] years,
p
=0.003), had higher WBC counts (11,400 [8,500-16,000] /μL vs. 9,900 [7,162.5-13,297.5] /μL,
p
=0.009), and had lower CK-MB levels (38.5 [18.0-75.3] U/L vs. 73.0 [42.5-137.0] U/L,
p
<0.001), than the non-early recovery group. In the histological diagnosis, the proportions of lymphocytic and eosinophilic myocarditis were similar between the two groups, whereas the proportions of giant cell myocarditis tended to be higher in the non-early recovery group. Multivariate analysis showed the independent predictors of early recovery were age ≤40 years (OR: 3.25; 95% CI: 1.42-7.44), WBC ≥ 11,000 /μL (OR: 3.10; 95% CI: 1.39-6.86) and CK-MB ≤ 61 U/L (OR: 2.46; 95% CI: 1.06-5.72), and if all conditions were fulfilled, the early recovery rate increased to 61.5%.

Conclusions:
Early recovery group had higher inflammatory parameter levels but lower myocardial damage marker levels on admission in addition to age ≤40 years, suggesting that patients having a strong acute-phase inflammatory response with a lower degree of myocardial damage, could recover earlier.
Abstract 4134863: Major Cardiovascular Events Following Non-Cardiovascular Surgeries in Minority Patients Compared to White Patients
Authors: Goyal Jatin , Elkamel Erij , Alarcon Sebastian , Castro Grettel , Rodriguez de la Vega Pura , Seetharamaiah Rupa , Ricardo Ruben , Vaidean Georgeta
Published: November 2024

Introduction:
Racial disparities are pervasive in cardiovascular outcomes. Although disparities following cardiovascular surgery have been extensively studied, fewer current, nationwide reports exist for postoperative outcomes in non-cardiovascular surgery.

Research Aim:
To investigate the incidence of 30-day post-operative major adverse cardiac, cerebral and thrombotic events (MACCTE) following non-cardiovascular surgeries in non-White patients as compared to White patients.

Methods:
This retrospective cohort study used the 2018-2022 National Surgical Quality Improvement Program database. Patients aged 18 or older who underwent non-cardiovascular surgeries (general, gynecology, neurosurgery, orthopedics, otolaryngology, plastics, thoracic, urology, obstetrics, and interventional radiology) were included. Race/ethnicity was categorized as non-Hispanic White (Whites), Hispanic, non-Hispanic Asian (Asians), non-Hispanic Black or African American (Blacks), and non-Hispanic Others. MACCTE was defined as a composite of death, MI, cardiac arrest, stroke, PE, or DVT. Five multivariable logistic regression models were used to hierarchically adjust for age, gender, ASA class, surgical subspecialty, operation time, transfer status, and all other comorbidities.

Results:
Among the 3,775,920 patients: 70.9% were Whites, 11.8% Hispanics, 4.1% Asians, 11.6% Blacks, 1.5% of Other race, 58.9% female, and 46.7% had an ASA classification of 3 or greater. The MACCTE incidence was 1.95% overall and 2.01% in Whites, 1.27% Hispanics, 1.48% Asians, 2.11% Blacks, and 1.69% Others. Compared to Whites, Blacks had higher incidences of cardiac arrest (0.40% vs. 0.23%), stroke (0.17% vs. 0.15%), PE (0.47% vs. 0.34%), and DVT (0.55% vs. 0.48%), and Asians (0.18% vs 0.15%) and Others (0.21% vs. 0.15%) had a higher incidence of stroke (p<0.001). With Whites as reference, the crude odds ratios, OR (95% CI) were 0.63 (0.61-0.65) in Hispanics, 0.73 (0.70-0.76) Asians, 1.05 (1.03-1.07) Blacks, and 0.84 (0.78-0.89) Others. The fully adjusted model odds ratios, OR (95% CI) were 0.88 (0.82-0.95) Hispanics, 0.89 (0.80-1.00) Asians, 1.11 (1.04-1.18) Blacks, and 0.80 (0.69-0.94) Others.

Conclusion:
Black patients experienced a higher MACCTE risk compared to Whites, even after adjustment for age, sex, ASA class, type of surgical procedure, and other comorbidities. These findings emphasize the importance of implementing comprehensive measures to prevent excess risk and promote equitable surgical care.
Abstract 4134877: Sexual Minorities Cardiovascular Health Disparities Compared to Heterosexual Adults in the US: A Systematic Review and Meta-Analysis of Nearly 2 Million Cohort Patients
Authors: Queiroz Ivo , Barbosa Lucas , Defante Maria Luiza Rodrigues , X. Mendes Beatriz , Tavares Arthur , Mesquita Cynthia , Mazetto Roberto , Antunes Vanio do Livramento Junior , Guida Camila , Caceres Billy
Published: November 2024

Background:
Cardiovascular disease (CVD) remains a leading cause of death globally, yet disparities in CVD outcomes among sexual minorities compared to heterosexual adults are under-researched. Sexual minorities face unique stressors, discrimination, and barriers to healthcare, which may contribute to higher CVD risk. This meta-analysis synthesizes evidence on health disparities between sexual minorities and heterosexual adults.

Methods:
We searched MEDLINE, Cochrane, and Embase databases for studies published between 2002 to 2024 that compared cardiovascular health disparities between sexual minorities and their heterosexual counterparts. Outcomes were CVD, Diabetes, Hypertension, and Obesity. We pooled odds ratios (OR) for binary endpoints with 95% confidence intervals (CI) using a random-effects model. Statistical analyses were performed using R software version 4.3.2.

Results:
We included 9 Cross-sectional studies after minimizing population overlap, comprising 1,938,814 patients with a mean age of 47 years. There were no significant differences in the odds of CVD (OR 1.10; 95% CI 0.87 to 1.39; Figure 1 A), Diabetes (OR 0.88; 95% CI 0.74 to 1.04; Figure 1 B), hypertension (OR 1.07; 95% CI 0.97 to 1.19; Figure 2 A) and Obesity (OR 1.01; 95% CI 0.76 to 1.35; Figure 2 B) between groups. In subgroup analysis, there were higher odds of obesity in the sexual minority population when compared to their heterosexual counterparts (OR 1.29; 95 % CI 1.15 to 1.45) and higher hypertension odds in sexual minority men (OR 1.35; 95% CI 1.12 to 1.63).

Conclusion:
In this meta-analysis, we found no statistically significant difference in the prevalence of CVD, diabetes, and obesity between sexual minorities and heterosexuals, meaning that more studies are necessary to assess this difference. Subgroup analyses revealed sexual minority men had higher odds of hypertension and sexual minority women for obesity.
Abstract 4134878: Single Perclose Plus Angioseal Versus Double Perclose for Percutaneous Femoral Access: A Systematic Review and Meta-Analysis
Authors: Bertolino Enrico , Monteiro Mastra Fontoura Milena , Pimentel Junior Dilson , Fernandez Miguel , Mesquita Cynthia , Queiroz Ivo , Diaz Braiana , Barbosa Lucas , Mulatti Grace
Published: November 2024

Background:
Vascular Closure utilizing Suture Based Devices (SBD) is an established approach for large-bore arterial access in percutaneous procedure patients. Standard of care uses two devices when accessing the artery with 8 Fr sheaths and above. The bailout use of Plug-based devices (PBD) is well established, but little is known about the intentional combination of SBD with PBD and how this technique compares to the standard approach. We aimed to compare these different approaches in this meta-analysis.

Methods:
PubMed, Scopus, and Cochrane databases were searched for observational studies comparing the hybrid approach to the standard one utilizing exclusively SBDs for arterial closure in large bore vascular access and reported the outcomes of (1) Access-related complications (ARC); (2) Major bleeding; (3) All bleeding events; (4) Need for surgical intervention; (5) Need for endovascular intervention ; (6) Device failure; (7) Pseudoaneurysm. Heterogeneity was examined with I2 statistics. A random-effects model was used for all outcomes.

Results:
We included five observational studies with 1,586 patients, of whom 1,489 (93.8%) underwent TAVI and 97 (6.1%) EVAR. Sheath size had an average of 20.56 Fr in the EVAR patients. ARC (RR 0.48; 95% CI 0.28-0.81; p<0.01), major bleeding (RR 0.29; 95% CI 0.19-0.44; p<0.01), all bleeding events (RR 0.36; 95% CI 0.23-0.56; p<0.01), surgical intervention (RR 0.28; 95% CI 0.10-0.78; p=0.01), or endovascular intervention (RR 0.53; 95 % CI 0.28-0.98; p=0.04), and device failure (RR 0.28; 95% CI 0.11-0.72; p<0.01) were significantly less common in patients treated with the hybrid technique compared to standard care. Pseudoaneurysm (RR 1.13; 95% CI 0.57-2.25; p=0.71) was not significantly different between groups.

Conclusion:
These findings suggest the hybrid technique, was associated with fewer access complications compared to the standard double SBD as a closure strategy in patients with large bore arterial access.
Abstract 4134896: Clinical and Echocardiographic Markers for the Prediction of Incident Atrial Arrhythmias in Hypertrophic Cardiomyopathy
Authors: Kotlo Srisha , Chiou Tommy , Akingbade Ololade , Kanelidis Anthony , Campagna Rachel , Kim Gene , Beaser Andrew , Slivnick Jeremy
Published: November 2024

Introduction:
Hypertrophic cardiomyopathy (HCM), in addition to increasing the risk for heart failure and sudden cardiac death, augments the risk for atrial fibrillation (AF) and atrial flutter (AFL). We aimed to identify clinical and echocardiographic risk factors that are predictive of incident AF/AFL in HCM patients.

Methods:
This retrospective study included 99 HCM patients from University of Chicago without prior AF/AFL, followed for a median of 3.2 years (IQR: 11.5 months-6.9 years). Clinical data were obtained via chart review; echocardiographic findings were obtained using AI software (Us2.ai) with measurements audited by a level III echocardiography reader. Statistical testing included Chi-square/Fisher’s exact (categorical variables) and T-test/Wilcoxon rank sum (continuous variables). Univariate and multivariate Cox regressions assessed predictive value of risk factors for AF/AFL.

Results:
18 HCM patients (18%) developed AF/AFL (
Table 1
). On univariate analysis, older age (HR 1.06, 95%CI 1.02-1.11, p=0.002), hypertension (HR 8.32, 95%CI 1.10-63.20, p=0.04), diabetes (HR 3.90, 95%CI 1.51-10.03, p=0.005), prior stroke (CVA, HR 3.81, 95%CI 1.34-10.86, p=0.012), and NYHA class II-IV (HR 8.48, 95%CI 2.97-24.21, p<0.001) predicted AF/AFL. E/A (p=0.04), E/e’ (p=0.028), MV-A (p=0.022), and LVEF (p=0.02) were also significant predictors (
Figure 1
). LVEF (HR 0.92, 95%CI 0.87-0.98, p=0.013) remained a significant predictor of AF/AFL on multivariate analysis controlling for age, hypertension, diabetes, CAD, CVA, and NYHA class.

Conclusions:
Traditional risk factors including age, hypertension, diabetes, CVA, and NYHA class are significant predictors of incident AF/AFL in HCM patients, highlighting the need for comprehensive risk factor evaluation. Even after adjustment for these clinical markers, LVEF independently predicts new AF/AFL in HCM patients, underscoring the importance of routine echocardiographic assessment for risk stratification in this patient population.
Abstract 4134911: Coronary Artery Calcium Predicts Cardiovascular Events in Individuals with Controlled Atherosclerotic Risk Factors: A Multi-Cohort Study
Authors: Mousavi Idine , Al Rifai Mahmoud , Blaha Michael , Erbel Raimund , Nasir Khurram , Virani Salim , Blumenthal Roger , McEvoy John , Stang Andreas , Schramm Sara , Schmidt Boerge , Al-Mallah Mouaz , Cainzos Miguel , Ballantyne Christie , NAMBI VIJAY
Published: November 2024

Background:
There is residual risk of atherosclerotic cardiovascular disease (ASCVD) that remains despite adequate risk factor (RF) control. Coronary artery calcium (CAC) has demonstrated value in ASCVD risk stratification. We evaluated the value of CAC in identifying residual risk of ASCVD events among those with traditional RF control.

Methods:
Participants without clinical ASCVD were pooled from the Multi-Ethnic Study of Atherosclerosis, Heinz Nixdorf Recall Study, Framingham Heart Study, and Jackson Heart Study. RF control was classified as “guideline-concordant” and “optimal” (Figure 1). Participants were stratified by the number of controlled RFs at baseline and CAC score (CAC = 0, 1-99, ≥100). Cox proportional hazards models examined the association between CAC and incident ASCVD events.

Results:
The study included 14,780 individuals (mean age 58 years (SD: 11), 54% female, 59% White, 27% Black, 50% CAC = 0). Over a median follow-up of 14.6 years, there were 1,441 incident ASCVD events. The distribution of CAC and ASCVD event incidence is shown in Panel A; 10% of those with 3 optimal RFs and 19% of those with 3 guideline-concordant RFs controlled had CAC

>

100. The rate of ASCVD events decreased with more RFs controlled and increased with higher CAC. Overall, optimal RF control was associated with lower ASCVD event rates compared to guideline-concordant control. At every level of RF control, CAC
>
100 was associated with increased HRs for incident ASCVD (Panel B). Those with CAC ≥ 100 and controlled RFs experienced ASCVD rates numerically comparable to or exceeding those with uncontrolled RFs but CAC = 0 (Panel A). Adjusted HR (95% CI) for ASCVD events with CAC
>
100 compared to CAC = 0 was 5.0 (2.0, 12.9) in optimal RF control and 3.7 (2.6, 5.4) in guideline-concordant RF control.

Conclusion:
There is significant heterogeneity in residual ASCVD risk among those with optimal or guideline-concordant traditional RF control and CAC can help identify this risk. Irrespective of RF control, a higher CAC burden was associated with increased ASCVD risk. Future studies could use CAC testing to identify those with higher residual ASCVD risk despite effective traditional RF control to target for novel therapies.
Abstract 4134967: Pericardial Adipose Tissue Hypertrophy Contributes to Heart Failure via β3 Adrenergic Signaling-Mediated Activation of the TGFβ1 Pathway
Authors: Hashimoto Masaki , Ueda Kazutaka , Adachi Yusuke , Sowa Hiroyuki , Zhai Bowen , Karasaki Kohei , Takeda Norihiko , Komuro Issei
Published: November 2024

Background:
The heart is surrounded by pericardial adipose tissue (PeAT). An increase in PeAT volume has been associated with the development of heart failure; however, the precise molecular mechanisms by which hypertrophic PeAT contributes to heart failure remain to be elucidated.

Aims:
To clarify the involvement of PeAT hypertrophy in the development of heart failure.

Methods:
Male C57BL/6 mice (8-10 weeks old) were fed a high-fat diet (HFD) for 8 weeks to induce PeAT hypertrophy. Cardiac pressure overload was induced by transverse aortic constriction (TAC) with a 26-gauge needle.

Results:
PeAT volume significantly increased in HFD-fed mice compared to those on a normal diet (ND) (25.28 ± 4.1 mg vs. 9.35 ± 0.73 mg, p<0.01). Eight weeks after TAC, HFD-fed mice (TAC+HFD) exhibited more pronounced cardiac dysfunction (fractional shortening: 45.21 ± 2.21% vs. 55.99 ± 1.91%, p=0.002, left ventricular mass: 130.3 ± 7.80% vs. 106.8 ± 3.77%, p=0.0154), upregulation of cardiac fibrosis-related genes (
Col1a1
,
Col3a1
), and greater fibrotic area in the left ventricle compared to ND-fed TAC mice (TAC+ND). Simultaneously, the TGFβ/Smad pathway was activated in the left ventricles of TAC+HFD mice. Notably, surgical removal of hypertrophic PeAT improved cardiac function in TAC+HFD mice, while transplantation of PeAT from HFD-fed mice into TAC+ND mice worsened cardiac function. In TAC+HFD mice, local noradrenaline concentration in PeAT decreased, along with reduced activation of hormone-sensitive lipase, a downstream target of β3 adrenergic receptor signaling. Local free fatty acid concentrations also decreased in the PeAT of HFD-fed mice. In the RAW 264.7 macrophage cell line, a decrease in palmitic acid, a major fatty acid, led to increased expression of TGFβ1.

Conclusions:
These results suggest that HFD-induced PeAT hypertrophy suppresses β3 adrenergic receptor signaling and free fatty acid release, increasing TGFβ1 expression in the macrophages and resulting in cardiac fibrosis and dysfunction. Our findings provide new insights into the pathogenesis of PeAT hypertrophy in heart failure development.
Abstract 4135035: Liver kinase B1 (LKB1) loss links vascular smooth muscle cell fate switch to aortic aneurysm formation
Authors: Cai Zhaohua , Satyanarayana Ganesh , Zhao Fujie , He Ben , Zou Ming-hui
Published: November 2024

Background:
Acquisition and maintenance of vascular smooth muscle cell (VSMC) fate are important for vascular development and homeostasis; however, little is known about the key determinant for VSMC fate and vascular homeostasis.

Methods:

Lkb1
flox/flox

;
Tagln-
Cre,
Lkb1

flox
/flox

;
Myh11-Cre/ERT2
, and lineage tracing

Lkb1
flox/flox

;
Myh11-Cre/ERT2
;

ROSA
mT/mG

mice were generated to study the impact of Lkb1 on VSMC and vascular function
in vivo
. Single aortic cells isolated from wild-type and

Lkb1
flox/flox

;
Myh11-Cre/ERT2
mice were analyzed by single-cell RNA sequencing (sc-RNA seq). The dynamic changes of vascular morphology and VSMC fate were investigated using high-frequency ultrasound and various histological techniques. In addition, VSMC phenotype and molecular mechanisms were further explored by mouse arterial ring assay
ex vivo
, in cultured human aortic VSMC
in
vitro, and in human aneurysmal aortic tissues.

Results:
We found that SMC-specific
Lkb1
ablation in

Lkb1
flox/flox

;
Tagln-Cre
mice caused severe vascular abnormalities and embryonic lethality. SMC-specific deletion of
Lkb1
in tamoxifen-inducible

Lkb1
flox/flox

;
Myh11-Cre/ERT2
mice spontaneously and progressively induced aortic/arterial dilation, aneurysm, rupture, and premature death. Sc-RNA seq and imaging-based lineage tracing showed that
Lkb1
-deficient VSMCs transdifferentiated gradually from early modulated VSMCs to fibroblast-like and chondrocyte-like cells, leading to ossification and blood-vessel rupture. Moreover, we found that SMC-specific
Lkb1
ablation resulted in decreased vascular contractility and hypotension
in vivo
. Mechanistically, Lkb1 regulates polypyrimidine tract binding protein 1 (Ptbp1) expression and controls alternative splicing of pyruvate kinase muscle (PKM) isoforms 1 and 2. Lkb1 loss in VSMC results in an increased PKM2/PKM1 ratio and alters the metabolic profile by promoting aerobic glycolysis. Treatment with PKM2 activator TEPP-46 rescues VSMC transformation and aortic dilation
in

Lkb1
flox/flox

;
Myh11-Cre/ERT2
mice. Furthermore, we found that Lkb1 expression decreased in human aortic aneurysm tissue compared to control tissue, along with changes in markers of VSMC fate.

Conclusions:
Lkb1, via its regulation of Ptbp1-dependent alterative splicing of PKM, maintains VSMC in contractile states and sustains vascular homeostasis. Our findings have important implications for understanding the pathogenesis of aortic aneurysm.
Abstract 4135095: Outcomes of Atrial Fibrillation Patients with Thrombocytopenia: Insights From a Nationwide Database
Authors: Younes Ahmed , Maraey Ahmed , Elzanaty Ahmed
Published: November 2024

Background:
While anticoagulation is crucial for atrial fibrillation (AF) patients to prevent ischemic events, those with thrombocytopenia have a potential increased risk of bleeding. This study examines the outcomes of hospitalized AF patients with thrombocytopenia.

Methods:
The National Inpatient Sample (NIS) from 2016-2020 was analyzed to identify adult patients with AF and thrombocytopenia (using the proper ICD-10 codes). Multivariate logistic and regression analyses were performed after adjusting for multiple patient and hospital confounders to compare outcomes between patients with and without thrombocytopenia. The primary outcome was all-cause inpatient mortality. Secondary outcomes included major bleeding (defined as gastrointestinal, intracranial, pulmonary, or unspecified bleeding), hypovolemic shock, packed red blood cell (pRBC) transfusion, ischemic stroke, length of stay (LOS), and total charges.

Results:
Among 2,016,244 AF admissions, 75,545 patients (3.75%) had thrombocytopenia. Thrombocytopenia was associated with increased inpatient mortality (adjusted odds ratio [aOR] 2.47, 95% CI 2.21-2.77, p < 0.001). Thrombocytopenia was also associated with increased risk of major bleeding (aOR 1.99, 95% CI 1.8-2.19, p < 0.001), hypovolemic shock (aOR 3.11, 95% CI 2.29-4.24, p < 0.001), pRBC transfusion (aOR 3.07, 95% CI 2.8-3.37, p < 0.001). There was no significant difference in ischemic stroke risk (aOR 0.67, 95% CI 0.37-1.21, p < 0.19) but thrombocytopenia was associated with longer LOS (aMD 1.5 days, 95% CI 1.41-1.59, p < 0.001) and higher total charges (aMD $16,508, 95% CI 14,805-18,211, p < 0.001).

Conclusions:
Thrombocytopenia in hospitalized AF patients is associated with increased mortality, bleeding risk, and healthcare costs, with no clear impact on ischemic stroke. These findings highlight the need for careful risk-benefit assessment and individualized management strategies for this vulnerable patient population.
Abstract 4137274: Optimal Timing of Pharmacoinvasive Strategy and its Impact on Clinical in Patients with ST-Elevation Myocardial Infarction: a Real-World Perspective
Authors: Stephanus Andrea , Pacheco Santos Alice , Machado Rodrigues da Cunha Ana Carolina , Augusto Rocha Ana Carolina , de Amorim Meireles Amanda , Guimaraes Souza de Oliveira Mariana , Arissa Coelho Matsunaga Pietra , de Sousa Munhoz Soares Alexandre Anderson , Cavalcante Nogueira Ana Claudia , de J B de Almeida Guimaraes Adriana , de Almeida Alexim Gustavo , Campos-Staffico Alessandra , Carvalho Luiz Sergio
Published: November 2024

Background:
Pharmacoinvasive strategy remains the cornerstone therapy for ST-elevation myocardial infarction (STEMI) where primary percutaneous coronary intervention (PCI) is unfeasible. Guidelines recommend PCI within 2 to 24 hours post-fibrinolysis. However, meta-analysis suggests that a shorter interval (<4h) between fibrinolysis and PCI (lysis-PCI time) significantly reduces the 30-day risk of death and reinfarction. Real-world applicability is limited due to trial exclusions of elderly patients and those with chronic kidney disease. This study aims to evaluate the impact of lysis-PCI timing on in-hospital mortality and major adverse cardiovascular events (MACE).

Hypothesis:
We hypothesize that shorter lysis-PCI times (<9h) increase in-hospital mortality and MACE, especially in patients over 80 years.

Goals:
To determine the impact of lysis-PCI timing on in-hospital mortality and MACE in STEMI patients.

Methods:
This retrospective cohort study of 1,043 STEMI patients in Brasília, Brazil, used multivariable categorical logistic regression models to assess the association of three lysis-PCI intervals (<9h; 9-18h; >18h) with in-hospital mortality and 4p-MACE (death, acute myocardial infarction, stroke, heart failure). Propensity score matching (1:1) was used to adjust for cardiovascular risk factors. Statistical significance was set at p<0.05.

Results:
The lysis-PCI timing groups showed no significant differences in admission Killip class, GRACE score, or age. However, the <9h group had higher incidences of in-hospital mortality (p=0.004), heart failure (p=0.002), cardiogenic shock (p=0.001), cardiac arrest within 24 hours (p=0.003), minor bleeding (p=0.006), and MACE (p=0.002). Multivariable categorical logistic regression revealed that each 4-h delay in lysis-PCI time reduced the risk of death (HR 0.560, 95% CI 0.381-0.771; p=0.001) and MACE (HR 0.877, 95% CI 0.811-0.948; p=0.001). These findings remained consistent after propensity score analysis (death: HR 0.721, 95% CI 0.516-0.956; p=0.034). Among patients older than 80, shorter lysis-PCI times were associated with increased mortality and MACE, even after propensity adjustment (Figure 1).

Conclusion(s):
Shorter lysis-PCI times (<9h) are associated with higher in-hospital mortality and MACE across all age groups, with a pronounced effect in patients over 80 years. These findings underscore the need for careful consideration of lysis-PCI timing, especially in elderly populations.
Abstract 4137448: Systemic Heparin Administration Does Not Inhibit microRNA Amplification in Patients with Myocardial Infarction
Authors: Barringhaus Kurt , Slone Sarah , Prousi George , Samani Stephanie , Freeburg Lisa , Churillo Amelia , Spinale Francis
Published: November 2024

Purpose:
MicroRNAs (miRs) have been proposed as biomarkers of myocardial infarction (MI), but prior evidence has demonstrated that heparin, commonly administered to patients presenting with MI, inhibits amplification during quantitative PCR (qPCR). The purpose of this study was to determine whether qPCR amplification of miRs is reduced in plasma of patients receiving heparin and if heparinase reverses this effect.

Methods:
Blood samples were collected and plasma recovered from patients with normal coronary arteries who had undergone CT coronary angiography (
N=5
) or who had received intravenous heparin at the time of invasive coronary angiography(
N=8
). Blood was also collected at the time of invasive coronary angiography from patients presenting with ST elevation MI (
N=9
). RT-qPCR was performed to quantify levels of 84 cardiac miRs, and Cel-miR-39-3p was utilized as a spike-in control. MiR qPCR was also performed following the addition of heparinase to plasma from 2 patients without MI treated with heparin and 2 patients presenting with MI who had received heparin.

Results:
Mean age of patients was 57 years, and 55% of patients were male. As compared with control patients, the cycle number for cel-miR-39-3p was significantly increased for patients receiving heparin (Figure 1a). No difference was seen in levels of cel-39-3p in heparin-treated patients with respect to the presence or absence of MI. Cel-miR-39-3p cycle times decreased when heparinase was added to samples from heparin-treated patients (Figure 1b). In contrast, heparin did not increase cycle times in any of the cardiac miRs tested, and cycle times decreased even further for miRs 499a-5p and 208b-3p in patients with MI (Figure 2).

Conclusions:
Systemic heparin treatment inhibits qPCR amplification of cel-mir-39-3p but does not inhibit endogenous miR amplification under these conditions. MiRs 499a-5p and 208b-3p are potentially important candidates for MI detection and quantification.
Abstract 4137461: Elevated Lipoprotein(a) Increases Cardiovascular-Related Healthcare Resources Utilization and Costs among US Medicare, Medicaid, and Commercial Enrollees with ASCVD
Authors: Hu Xingdi , Lozama Tony , Petrilla Allison , Agatep Barnabie , McMorrow Donna , Mohammadi Iman , Reisman Lonny , Wong Nathan
Published: November 2024

Background:
Elevated lipoprotein(a) [Lp(a)] is a recognized genetic, independent, and causal risk driver for atherosclerotic cardiovascular disease (ASCVD). Less is known about how elevated Lp(a) affects downstream cardiovascular (CV)-related healthcare resource utilization (HCRU) and costs in patients with ASCVD.

Objective:
To assess the association of Lp(a) levels with CV-related HCRU (hospitalizations, outpatient and emergency department [ED) visits), and CV-related costs for patients with ASCVD in a national-scale multi-insurance cohort.

Methods:
Patients with ASCVD were pooled from US Medicare, commercial, and Medicaid health plans from 2017 to 2022. Lp(a) levels (mg/dL and nmol/L) were linked at the patient level with HealthVerity Lab Data. Elevated Lp(a) was defined as Lp(a)≥70mg/dL (≥ 175 nmol/L) and normal Lp(a) was defined as Lp(a)<30mg/dL (<75 nmol/L). Generalized linear models with log link negative binomial distribution (HCRU) and log link gamma distribution (costs) adjusted for age, sex, race, insurance type, comorbidities, statin use, and prior hospitalizations, measured the association of Lp(a) levels with the annualized rate of CV-related hospitalizations, ED visits, and outpatient visits (incidence rate ratio [IRR]) and CV-related costs (annualized cost ratio).

Results:
A total of 180,240 ASCVD patients were identified with Lp(a) values. Median (IQR) Lp(a) was 14 mg/dL (4 mg/dL – 48 mg/dL) or 35 nmol/L (12 nmol/L – 114 nmol/L). Mean (SD) age was 68.6 (12.0) years with 49.9% being female; 72.8% of patients were from Medicare, followed by commercial (21.8%) and Medicaid (5.4%). Fully adjusted CV-related HCRU was significantly higher in those with elevated Lp(a) compared to normal Lp(a): inpatient hospitalizations (IRR=1.11), outpatient visits (IRR=1.11) and ED visits (IRR=1.06), all p <0.001 (IRR and 95% CI reported in Table 1). Patients with elevated Lp(a) had 14% higher CV-related annualized healthcare costs than patients with normal Lp(a) (p <0.001) with significantly higher CV-related HCRU beginning with Lp(a) levels >30 mg/dL (>75 nmol/L).

Conclusion:
Elevated Lp(a) was significantly associated with greater CV-related HCRU and costs in patients with ASCVD.
Abstract 4137467: Intravascular ultrasound-guided versus angiography-guided percutaneous coronary intervention: A systematic review, meta-analysis, and meta-regression of randomized controlled trials
Authors: Rahman Asad , Ahmed Mushood , Nadeem Zain , Javaid Hira , Jain Hritvik , Ahsan Areeba , Ahmad Adeel , Shahid Farhan , Ahmed Raheel
Published: November 2024

Background:
Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) allows better visualization of atherosclerotic plaques than angiography alone. We conducted a systematic review and meta-analysis to comprehensively synthesize the available evidence regarding the efficacy of IVUS-guidance compared to angiography-guided PCI. Moreover, we conducted a sensitivity analysis to determine the applicability of IVUS guidance in complex PCI.

Methods:
We conducted a comprehensive literature search of major bibliographic databases from inception until May 2024 to identify randomized controlled trials (RCTs) comparing IVUS-guided versus angiography-guided PCI. Risk ratios (RR) with their corresponding 95% confidence intervals (CI) were pooled using the random-effects model, with a p-value <0.05 considered statistically significant. We conducted meta-regression to determine the moderating of baseline covariates on pooled outcomes.

Results:
Sixteen RCTs were included with 10,993 patients undergoing PCI (IVUS-guided PCI: 5684 patients; angiography-guided PCI: 5157 patients). IVUS-guided PCI demonstrated a significantly lower risk of cardiac death [RR: 0.49; 95% CI: 0.35, 0.68], major adverse cardiovascular events [RR: 0.64; 95% CI: 0.51, 0.80], myocardial infarction [RR: 0.73; 95% CI: 0.59, 0.89], stent thrombosis [RR: 0.45; 95% CI: 0.27, 0.75], target lesion revascularization [RR: 0.60; 95% CI: 0.49, 0.74], and target vessel revascularization [RR: 0.56; 95% CI: 0.45, 0.70] than angiography-guided PCI. IVUS-guided PCI demonstrated a nonsignificant trend toward a reduced risk of all-cause mortality [RR: 0.79; 95% CI: 0.61, 1.04]. Meta-regression showed a nonsignificant moderating effect of the duration of follow-up, age of patients, baseline dyslipidemia, and hypertension status on pooled outcomes. A sensitivity analysis was conducted for patients undergoing complex PCI. The sensitivity analysis showed the superiority of IVUS-guided PCI compared to angiography-guided PCI by resulting in a significant improvement in the clinical outcomes.

Conclusion:
This meta-analysis concluded that IVUS-guided PCI resulted in a reduction in cardiac death, major adverse cardiovascular events, myocardial infarction, stent thrombosis, target lesion revascularization, and target vessel revascularization, compared to angiography-guided PCI. Moreover, we observed the superiority of IVUS guidance in complex PCI as well.
Abstract 4137527: Evaluation of 10-Year Atherosclerotic Cardiovascular Risk Prediction Performance using the PREVENT versus Pooled Cohort Equations in a US Integrated Healthcare System
Authors: Zhou Hui , Zhang Yiyi , Zhou Mengnan , Choi Soon Kyu , Reynolds Kristi , Bellows Brandon , Moran Andrew , Colantonio Lisandro , Allen Norrina , Safford Monika , An Jaejin
Published: November 2024

Background:
The American Heart Association published the new PREVENT equations for estimating atherosclerotic cardiovascular disease (ASCVD) risk.

Question:
Do the PREVENT equations improve risk prediction for 10-year ASCVD compared with the pooled cohort equations (PCEs) in a large diverse population?

Aim:
To assess ASCVD risk prediction performance of the two PREVENT equations [PREVENT Base, PREVENT Base plus optional predictors including urine albumin-to-creatinine ratio, glycated hemoglobin, and social deprivation index (PREVENT Full)] compared with the PCEs.

Methods:
We included adults aged 40-75 years without a history of ASCVD or diabetes from Kaiser Permanente Southern California in 2009 and followed them through 2019. Outcome was incident ASCVD defined as myocardial infarction, fatal coronary heart disease, fatal and nonfatal stroke. We compared model discrimination (Harrell’s C), mean calibration (estimated as the ratio of predicted to observed event rates), and calibration curve among the overall population and stratified by sex and race/ethnicity.

Results:
Of the 559,111 adults (mean age 54, 11% Black, 32% Hispanic), 10,695 developed an ASCVD event during a median follow-up of 10 years. Harrell’s C among the overall population was 0.741 (95% CI 0.736-0.745) for PREVENT Base, 0.743 (0.738-0.748) for PREVENT Full, and 0.741 (0.736-0.746) for the PCEs (
Table
). Compared with the PCEs, both PREVENT equations improved Harrell’s C in men but not in women, and in Black adults but not in other racial/ethnic groups. Both PREVENT equations were well-calibrated (mean calibration ranged 0.83-1.37; calibration slope ranged 0.71-1.28), while the PCEs overestimated 10-year ASCVD risk (mean calibration ranged 1.80-2.20; calibration slope ranged 0.34-0.45) (
Table
&
Figure
).

Conclusion:
Compared with the PCEs, both PREVENT Base and Full equations improved calibration in predicting 10-year ASCVD risk, with minimal improvement in discrimination in men and Black adults only.
Abstract 4137531: A Pharmacist Medication Titration Program for Patients with Cardiac Sarcoidosis and Systolic Heart Failure
Authors: Sykora Daniel , Olson Nicole , Churchill Robert , Kim Boyoung , Bratcher Melanie , Elwazir Mohamed , Young Kathleen , Abou-Ezzeddine Omar , Bois John , Giudicessi John , Cooper Leslie , Rosenbaum Andrew
Published: November 2024

Introduction:
Cardiac sarcoidosis (CS) often results in systolic heart failure (HF) and responds favorably to guideline directed medical therapy (GDMT). A multidisciplinary team approach to HF care is recommended but few published examples exist in CS patients.

Methods:
We queried an institutional registry of 599 CS patients (2000-2023) for patients with index LVEF < 50% (within 90 d of index CS evaluation) and follow-up TTE within 11-36 months. In our CS medication therapy management (MTM) program (started 1/8/2019), pharmacists conduct independent visits with CS patients (in person or remote), discuss GDMT tolerance and symptoms, review monitoring laboratory studies, and adjust GDMT (ACEi/ARB/ARNi, beta-blocker, MRA, and/or SGLT2i) via collaborative practice agreement with the CS cardiologists. Patients were classified as MTM (≥1 MTM encounter) or NMTM patients (0 encounters). We compared (1) GDMT, (2) cardiac remodeling, and (3) clinical outcomes (event free survival to first heart failure hospitalization, LVAD, heart transplant, or death).

Results:
Nineteen percent (113/599) CS patients met inclusion criteria (34% female, 92% white, median age 57 y, 19% definite CS, 58% probable CS, 31% presumed CS), with 44 MTM (median 11.5 encounters, IQR 11) and 69 NMTM patients. Both MTM and NMTM patients were on a median 2 GDMT agents at index evaluation (p=0.21). At follow-up (median 19 mo MTM, 15 mo NMTM, p=0.05), MTM patients were on more GDMT agents than NMTM (median 3.0 vs 2.0, p<0.001), with higher % target dose of ACEi/ARB/ARNi (98% vs 71%, p=0.009), beta-blocker (87% vs 57%, p=0.004), and SGLT2i use (30% vs 9%, p=0.004), but similar MRA use (48% vs 32%, p=0.09). Immunosuppressive therapy was used in 88% patients (89% MTM vs 87% NMTM, p=0.79). Index LVEF was similar (MTM 36%, NMTM 32%, p=0.07). Mean change in LVEF (excluding LVAD/transplant patients) demonstrated a non-significant trend towards improved remodeling in MTM (+8.6%) vs NMTM patients (+5.5%; p=0.39). MTM patients exhibited lower risk of the clinical outcome (1/44 MTM vs 16/69 MTM patients; univariable HR 0.08 [95%CI 0.01 - 0.63], log-rank p=0.016).

Conclusions:
A pharmacist MTM program for CS patients with HF is associated with improved GDMT uptitration and clinical outcomes, emphasizing the value of collaborative multidisciplinary CS care.