bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4146022: Serology supportive of recent coxsackievirus B infection is correlated with Multisystem Inflammatory Syndrome in Children (MIS-C)
Authors: Kordi Ramesh , Chang Arthur , Hicar Mark
Published: November 2024

Background:
Rarely, SARS-CoV-2 will lead to myocarditis associated with Multisystem Inflammatory Syndrome in Children (MIS-C). It remains unclear why MIS-C only targets specific children. Coxsackieviruses (CV) are prevalent infections during childhood and, like SARS-CoV-2, can lead to viral myocarditis. To explore an association with MIS-C we investigated the sero-epidemiology of CV in admitted pediatric patients.

Method:
A retrospective case control study was performed by chart review of children (age ≤ 21) admitted to a tertiary care hospital with CV serological testing from January 2017 to August 2023. Clinical, laboratory and imaging findings were used to classify patients as MIS-C and CV-unlikely or CV-possible for non-MIS-C patients.

Results:
Out of 182 admissions (179 patients, median age 6), CVB complement fixation (CF) assay on serotypes B1-B6 and CVA immunofluorescence assay IgG on serotypes A7, A9, A16, and A24 were positive in at least one serotype in 59.2% and 80.7% of cases respectively. We observed a significant drop in CVB CF seropositivity during the peak of social distancing in 2020. The CVB titers in CV-possible cases and MIS-C were similar. The likelihood of elevated CVB CF titers was significantly higher in MIS-C than CV-unlikely group (OR: 1.92, 95% CI: 1.02-3.63,
p
: 0.04). CVB CF titer trended toward higher values in African Americans compared to Whites (OR: 1.57, 95% CI: 0.98-2.50,
p
-value:0.057). As previously shown, the frequency of MIS-C was considerably higher in African Americans than Whites (18.1%, versus 9%,
p
: 0.1).

Conclusion:
Higher likelihood of elevated CVB CF titers in patients with MIS-C and in African Americans along with a notable higher frequency of MIS-C in African Americans warrant further investigation into the role of CVB infection in MIS-C development.
Abstract 4146032: Routine stress testing in diabetic patients after coronary intervention: a systematic review and single arm meta-analysis
Authors: Oliveira Juan Peres de , HUNTERMANN RAMON , De Oliveira Fischer Bacca Caroline , da Rocha Franciani , de Oliveira Raissa
Published: November 2024

Background:
Stress testing is a well-established non-invasive method commonly used in clinical practice for patients with angina. However, its benefit in diabetic patients after coronary intervention remains unclear. This systematic review aims to address this knowledge gap by evaluating the impact of routine stress testing in this specific patient population.

Research Question:
Does routine stress testing improve outcomes in diabetic patients with prior revascularization?

Goals:
We aimed to perform a systematic review and meta-analysis of studies that evaluated death, MACE and repeated revascularization episodes in diabetic patients who have prior coronary intervention.

Methods:
We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCT) and cohort studies evaluating diabetic patients who underwent cardiac revascularization and reporting the following outcomes: (1) Myocardial Infarction (MI) and Cardiovascular Death; (2) Ischemia; and (3) Repeat Revascularization. Statistical analysis was performed using Open Meta and heterogeneity was assessed with I
2
statistical.

Results:
We included 16924 patients from 16 studies, of which 15 were observational cohort studies and 1 was a RCT. All patients were diabetics and had a history of revascularization. Follow-up ranged from 1 to 5.2 years. The mean patient age was 60.8±9.5 years and 75% were male. MI and cardiovascular death was found in 9.8% (95% CI; range 6.8-12.8%; p<0.01; (figure 1A), ischemia was found in 36.5% (95% CI; range 28.7-44.3%; p<0.01; (figure 1B) and revascularization was repeated in 16.3% (95% CI; range 4.9-27.7%; p<0.01; (figure 1C).

Conclusion:
Routine stress testing in diabetic patients with prior coronary intervention may not significantly alter the outcomes. These findings suggest that, while routine stress testing is a common practice for monitoring heart diseases in diabetic patients, its impact on improving clinical outcomes requires further investigation through controlled studies.
Abstract 4146053: Global Burden and Trend of Cardiomyopathy and Myocarditis in G20 Countries from 1990-2021: A secondary analysis from the Global Burden of Disease Study 2021.
Authors: Saravanabavanandan Ragavendar , Venugopal Darshine , Yadav Ratan Pal , Syed Saif , Lakkimsetti Mohit , Pudhota Harsha Choudary , Shandilya Ashwinikumar , AMIN VISHRANT , PATEL JUHI , Bhalodia Paritaben , DESAI HARDIK , sharma kamal
Published: November 2024

Introduction:
Cardiomyopathy (CM) and myocarditis rank as the fifth leading cause of death and disability in G20 countries amongst all cardiovascular disease related (CVD) deaths. Despite their escalating burden, there is a notable lack of consistent data across these nations. This study is the first to estimate the burden of these cardiac conditions over the last three decades, including the initial two years of the COVID-19 pandemic, highlighting the urgent need for improved surveillance and specific healthcare strategies to manage these critical health issues.

Method:
We estimated incidence, prevalence, deaths, disability-adjusted life years (DALYs), years lived with disability (YLDs) due to CM and myocarditis by age, sex, year and location across the G20 countries from 1990-2021 using global burden of disease 2021 methodology.

Results:
From 1990 to 2021, the total percentage change (TPC) in prevalence counts increased by 64% (95% Uncertainty Interval: 53% to 75%), incidence by 57% (47% to 68%), and deaths by 37% (26% to 49%). Japan had the highest age-standardized incidence rate (ASIR) at 19.84 (16.38-24.21) cases per 100,000, closely followed by Sweden at 19.74 cases per 100,000. The highest mortality rate (ASMR) was observed in Latvia at 27.95 (23.89-31.99) cases per 100,000, with Russia following at 26.3 cases per 100,000 in 2021. Poland recorded the highest YLD rate (ASYLDR) at 16.13 (11.05-22.86), with Sweden next at 15.67 per 100,000 in 2021. The highest incidence occurred in the 70-74 age group with 76,173 cases (46,415-113,840), with the most deaths in the 80-84 age group at 31,289 (27,390-33,741), and the highest DALYs in the 55-59 age group at 750,723 (680,540-814,890) in 2021. Regarding gender, the TPC in incidence for males was 55% compared to 61% for females, in deaths 57% for males versus 16% for females, and in YLDs 67% for males versus 54% for females from 1990 to 2021.

Conclusion:
Deaths due to CM and myocarditis accounted for 2.04% of all CVD deaths in G20 countries in 2021. The increasing burden highlights the need of proactive initiatives, including tailored health education and advanced screening programs. It should be prioritized to address the needs of the most affected demographics and regions. Integrating technology and cross-border healthcare collaborations could play a pivotal role in mitigating the impact of this condition and enhancing overall public health resilience.
Abstract 4146069:
18
F-NaF and
18
F-FDG and calcification predict the development of abdominal aortic aneurysms and is attenuated by drug therapy
Authors: Nakahara Takehiro , Miyazawa Raita , Iwabuchi Yu , Tonda Kai , Narula Nupoor , Strauss Harry , Narula Jagat , Jinzaki Masahiro
Published: November 2024

Background:
Abdominal aortic aneurysms (AAA) expand over time and increase the risk of fatal ruptures.

While large aortic diameter increases the risk of rupture, some AAA rupture at small diameters and some large aneurysms do not rupture. Therefore, identification of patients at increased risk of rapid AAA expansion and rupture is importance. To predict expansion, the isolated assessment of
18
F-fluorodeoxyglucose (FDG) and sodium fluoride (NaF) uptake or calcification volume in aneurysms has been investigated with variability in results. We systematically evaluated whether
18
F-FDG and
18
F-NaF uptake were predictive of AAA expansion.

Methods:
Seventy-four (74) male Sprague–Dawley rat AAA models were imaged using positron emission tomography-computed tomography (PET-CT) with
18
F-FDG and
18
F-NaF at 1, 2, 4, 6, and 8 weeks after CaCl
2
or saline stimulation. In the 1-week cohort (n=25), the correlation between
18
F-FDG or
18
F-NaF uptake and pathological markers was investigated. In the time-course cohort (n=49), animals received either atorvastatin, losartan, aldactone, or risedronate to assess the effect of these drugs, and the relationship between aortic size and sequential
18
F-FDG and
18
F-NaF uptake or calcification volume was examined.

Results:
In the 1-week cohort, the maximum standard unit value of
18
F-FDG and
18
F-NaF uptake correlated with CD68-(r=0.82, p=0.0010) and von Kossa staining-positive areas (r=0.89, p<0.0001), respectively.

In the time-course cohort,
18
F-FDG and
18
F-NaF uptake changed in a time-dependent manner and drugs attenuated this uptake. Specifically,
18
F-FDG showed high uptake at weeks 1 and 2, whereas a high
18
F-NaF uptake was noted throughout the study period. Although drugs suppressed
18
F-NaF and
18
F-FDG uptake, only atorvastatin significantly reduced aortic enlargement. Risedronate decreased the calcification volume; however, the aorta was significantly enlarged.

The final aortic area correlated well with
18
F-FDG and
18
F-NaF uptake and calcification volume, especially at 1 and 2 weeks [
18
F-NaF(1week): r=0.61,
18
F-FDG(2weeks): r=0.51, calcification volume(1week): r=0.59, p<0.0001]. Multiple linear regression analysis showed that the combination of these factors predicted the final aortic size, with
18
F-NaF uptake at 1 week being the strongest predictor.

Conclusion:
The uptake of
18
F-NaF and
18
F-FDG and the calcification volume at appropriate times correlated with the development of AAAs, with
18
F-NaF uptake being the strongest predictor.
Abstract 4146076: Lower atrial fibrillation recurrence with Polar X cryoballoon system in patients with persistent atrial fibrillation compared to Arctic Front Advance Pro system
Authors: Lee Hyo Jin , Kim Juwon , Kim Ju Youn , Park Seung-Jung , Park Kyoung-Min , ON YOUNG-KEUN
Published: November 2024

Background:
Cryoballoon ablation has been shown to be non-inferior to radiofrequency ablation in terms of efficacy and safety for atrial fibrillation (AF). However, the outcomes of newer cryoballoon ablation systems, such as PolarX, in patients with AF remain unclear.

Research Questions:
This study aimed to assess whether the PolarX cryoballoon ablation system offers superior AF-free survival and fewer complications compared to the established Arctic Front Advance Pro (AFA-Pro) system, particularly in patients with persistent AF.

Methods:
This retrospective cohort study included 217 consecutive patients diagnosed with AF who underwent cryoballoon ablation using either the AFA-Pro or PolarX systems at a single high-volume tertiary hospital between March 2023 and February 2024.

Results:
Patients were divided into two groups based on the cryoballoon ablation system used: the AFA-Pro group (n=100) and the PolarX group (n=117). Among those with persistent AF (n=68), there were 32 in the AFA-Pro group and 36 in the PolarX group. In the total patient cohort, the PolarX system did not significantly improve AF-free survival compared to the AFA-Pro system [hazard ratio (HR) 0.63, 95% confidence interval (CI) 0.32-1.25; p=0.18]. However, in the subgroup of patients with persistent AF, the PolarX system significantly improved AF-free survival compared to the AFA-Pro system (HR 0.26, 95% CI 0.08-0.80; p=0.01). The PolarX system was associated with a higher incidence of transient phrenic nerve palsy (PNP) compared to the AFA-Pro system [odds ratio (OR) 2.37, 95% CI 1.00-5.65; p=0.05], though it was not associated with permanent PNP. There were no significant differences in the rates of complications such as esophageal injury, cardiac tamponade, or vascular complications. Predictors of AF recurrence post-ablation included persistent AF (HR 2.80, 95% CI 1.41-5.56; p=0.01) and left atrium volume index (LAVI) (HR 1.03, 95% CI 1.00-1.06; p=0.04).

Conclusion:
The PolarX cryoballoon ablation system demonstrates comparable safety and efficacy to the AFA-Pro system in treating atrial fibrillation. The PolarX cryoballoon ablation system is associated with better AF-free survival compared to the AFA-Pro system in patients with persistent AF. LAVI may be a predictor of AF recurrence post-cryoballoon ablation.
Abstract 4146087: Danish Pragmatic Randomized Trial to Evaluate the Effect of HeartLogic-Guided Management on Heart Failure Outcomes – The DANLOGIC-HF Preliminary Registry Findings
Authors: Witten Davodian Lise , Dyrby Johansen Niklas , Sattler Stefan Michael , Wolsk Emil , Risum Niels , Kober Lars , Gustafsson Finn , Davodian Danny , Solomon Scott , Chien Christopher , Fudim Marat , Hernandez Adrian , Kwan Brian , Stolen Craig , Biering-Soerensen Tor
Published: November 2024

Background:
Hospitalizations due to heart failure (HF) are costly and detrimental to patient health. The HeartLogic (HL) algorithm has been found to be predictive of impending HF decompensation.

Purpose:
To present characteristics of the Danish nationwide DANLOGIC-HF population and preliminary findings on the performance of the HL algorithm.

Methods:
All Danish patients with a HL compatible device implanted after 2017 were identified. Their retrospective HL index values were used to calculate active alert periods. HF status and other diagnoses were based on ICD10 diagnoses codes, and patients with a CRT-D were categorized as having known HF regardless of ICD10 diagnoses. The association between HL alerts and HF hospitalizations were assessed using a Cox proportional hazard model with alert status as a time-dependent covariate and clustered standard errors.

Results:
In this population of 1599 adult patients with a CRT-D or ICD, mean age was 59.6 years,75% were male, and 26.9% had ischemic heart disease. While 43% had known HF, only 24% of the population had a CRT-D. Aside from diabetes (7.4% vs 2.7%, p<0.001) and chronic obstructive pulmonary lung disease (3.5% vs 0.5%, p>0.001) being more frequent in patients with HF, the prevalence of cardiovascular comorbidities was similar between patients. Patients with HF had a lower left ventricular ejection fraction (LVEF) (29% vs 44%, p<0.001) and higher NYHA class at implantation compared to patients without HF. Patients with HF also had a higher HF-related hospitalization rate (30 vs 7 per 100 patient-year, p<0.001).

At a mean follow-up time of 2.9 patient-years, HF at baseline and LVEF significantly modified the association between HL alert status and risk of HF hospitalization. The hazard ratio of being hospitalized with HF while in active HeartLogic alert was 7.9 [5.7, 11.1] for the entire population, 5.4 [3.8, 7.6] for patients with known HF and 14.7 [6.0, 36.4] for patients without known HF (p for interaction <0.001). For patients with a LVEF<40%, the hazard ratio for being hospitalized with HF if having an active HL alert was 7.1 [4.9, 10.6] compared with 33.7 [7.3, 157] for patients with a LVEF>40% (p for interaction = 0.026).

Conclusion:
Being in active alert was associated with a high risk of being hospitalized with HF, especially among patients without known HF. These findings emphasize the potential utility of HL-guided management in improving HF outcomes, both amongst patients with and without known HF.
Abstract 4146091: Transvenous Extraction of Quadripolar Coronary Sinus Pacing Leads Is Feasible and Safe
Authors: Wagner Ethan , Lewis Robert , Pokorney Sean , Hegland Donald , Piccini Jonathan
Published: November 2024

Introduction/Background:
Quadripolar coronary sinus (CS) leads are commonly employed in cardiac resynchronization therapy. There are limited data on extraction of these leads. The presence of additional electrode terminals on quadripolar leads (compared to unipolar or bipolar leads) has raised concerns about CS fibrosis and extraction difficulty.

Goals/Aims:
The purpose of this study was to examine the safety and efficacy of quadripolar CS lead extraction and CS lead reimplantation, and to compare outcomes with extraction of non-quadripolar (unipolar or bipolar) CS leads.

Methods/Approach:
In this retrospective cohort study, patients who underwent extraction of CS leads between 2013 and 2024 at a large tertiary care center were included. Outcomes of interest included rates of complete CS lead removal, complete procedural success, major adverse events, and successful reimplantation in the CS. Group means were compared using the two-sample t-test assuming independent samples and unequal variances. Nominal categorical variables were analyzed with the Chi-square test or Fisher exact test where appropriate. A p value less than 0.05 was considered significant.

Results/Data:
A total of 182 patients were included (n = 102 quadripolar leads and n = 80 non-quadripolar leads). The mean patient age was 68.0 ± 11.6 years and 22% were female. The mean CS lead age was lower in the quadripolar group (3.0 ± 2.7 years vs. 8.2 ± 4.3 years, p < 0.001), and the complete procedural success rate was higher (99% vs. 90%, p = 0.01). There was no significant difference in complete CS lead removal rates between groups (99% vs. 95%, p = 0.17). There were no major adverse events in the quadripolar group, and two major adverse events occurred in the non-quadripolar group. In the quadripolar group, manual traction alone was successful in 59%, laser sheaths were used in 39%, and rotational cutting tools were used in 9%. In the non-quadripolar group, manual traction alone was successful in 19%, laser sheaths were used in 79%, and rotational cutting tools were used in 26%. There was no significant difference in reimplantation success rates between groups (82% vs. 90%, p = 0.30).

Conclusions:
Quadripolar CS lead extraction had a high success rate and low rate of major adverse events. Reimplantation in the CS was possible with a good success rate but was limited by CS branch stenosis or occlusion.
Abstract 4146115: Contribution of Preload Elevation vs. Ischemia to Pro-Fibrotic Signaling and Interstitial Collagen Deposition in Swine with Chronic Coronary Artery Disease
Authors: Hudson Emily , Wadhwani Alexandra , Palka Beth , Canty John , Weil Brian
Published: November 2024

Introduction:
We recently observed that transient elevations in preload are common in swine with multi-vessel coronary artery disease (MV-CAD), presumably due to intermittent demand-induced ischemia of a large perfusion territory. Based on evidence that repetitive preload elevation can lead to fibrosis in the absence of ischemia, we hypothesized that mechanical stretch, rather than ischemia, maybe a key mechanism underlying extracellular matrix (ECM) remodeling in chronic CAD. To test this hypothesis, we compared regional pro-fibrotic gene expression and interstitial collagen in swine with MV-CAD to that observed in swine with single-vessel CAD (SV-CAD) in which the size of the culprit artery perfusion territory is insufficient to cause preload elevation during acute ischemia.

Methods:
Juvenile swine were instrumented with fixed 1.5 mm stenoses on the left anterior descending and left circumflex (LCx) coronary arteries (MV-CAD; n=6) or the LCx only (SV-CAD; n=6). Three months later, LV tissue was collected from the free wall (ischemic region) and posterior wall (non-ischemic region) to quantify pro-fibrotic gene expression (qPCR) and interstitial collagen (picrosirius red staining) vs. controls (n=11).

Results:
LCx stenosis severity was similar between MV-CAD and SV-CAD groups (90±4 vs. 82±7%; p=0.4). Pro-fibrotic gene expression was significantly elevated in both ischemic and non-ischemic regions within the MV-CAD group but was generally absent in animals with SV-CAD (
A
). This corresponded with a significant increase in interstitial collagen in ischemic and non-ischemic regions of the LV in animals with MV-CAD (
B
). In contrast, the SV-CAD group did not exhibit increased interstitial collagen in either the ischemic or non-ischemic region of the LV vs. controls.

Conclusion:
Pro-fibrotic gene expression and interstitial collagen are not altered in swine with chronic LCx stenosis, suggesting that ischemia alone may not be sufficient to elicit ECM remodeling. Conversely, swine with MV-CAD exhibit an increase in pro-fibrotic gene expression and interstitial collagen that is not restricted to the ischemic area of the LV, implicating repetitive preload elevation as a potential mechanism underlying ECM remodeling in CAD.
Abstract 4146119: Coronary fistula as a rare etiology of refractory angina in elderly
Authors: Del Vecchio Ziotti Sara , grobe sarah , Pereira Thiago , Menezes Machado de Mendonça Caio , Dourado Luciana , Rosal Marcelly , Palacio de Azevedo Renato , CESAR LUIZ , Gowdak Luis
Published: November 2024

Introduction:
Refractory angina (RA) is a challenging and debilitating condition in the presence of myocardial ischemia regardless of a combination of antianginal drugs and revascularization procedures. Among the phenotypes of RA, there is angina in the absence of obstructive coronary disease (ANOCA). Coronary artery fistulas (CAF) are rare connections between coronary arteries and heart chambers or vessels. 3% of CAF drain into the left ventricle (LV), which can lead to the coronary steal phenomenon and angina in the form of ANOCA. We report here under a case of symptomatic chronic coronary syndrome (CCS) and CAF.

Case Report:
An 85-year-old woman with CCS had angina progression, reaching functional class 3 and frequent need of nitrate use, despite the use of three antianginal drugs. Stress myocardial perfusion scintigraphy showed reversible hypoperfusion in the lateral, inferolateral and inferior LV walls. A coronary angiogram was performed, revealing the absence of obstructions. However, CAF for the LV was identified around the ischemic territory. It was decided to start our Alopurinol protocol for RA. A treadmill test was done before and after the treatment to assess time to angina occurrence and ST segment change. After 3 months, there were an improvement in the threshold and intensity of angina (class 2) and reduction in nitrate need. In a new scintigraphy, normalization of perfusion was observed, and a new treadmill test showed reduction of 4.1 minutes for angina occurrence with an increase of 1.7 mets and no difference in ST change.

Discussion:
CAF are rare, identified in up to 0.2% of angiograms. They can lead to heart failure (HF), myocardial ischemia and arrhythmias. Treatment is based on the clinic, the patient's age and the hemodynamic significance of the CAF. For adults, one of the indications for CAF occlusion is the presence of myocardial ischemia. However, the association between RA and CAF is rarely described in the literature. In the present report, we illustrate the case of an octogenarian with RA, ANOCA and FAC who, before considering interventional treatment, underwent medical optimization with excellent response and improvement in cardiac perfusion and exercise tolerance.

Conclusion:
In the scenario of RA and ANOCA, a combination of different antianginal drugs can promote symptoms control and improvement of myocardial perfusion and exercise performance, even in the face of uncommon causes such as the one here reported.
Abstract 4146125: Demographic, Regional Trends and Place of Death of Cardiovascular Disease−Related Mortality in Colorectal Cancer in the United States (1999 to 2020)
Authors: Yasmin Farah , Asghar Muhammad Sohaib , Shaharyar Maryam , Ochani Rohan Kumar , Alraies M Chadi , Surani Salim
Published: November 2024

Background:
Patients with colorectal cancer (CRC) are 2-4 times more likely to develop cardiovascular disease (CVD), likely due to shared risk factors and the effects of chemo-radiotherapy. Despite existing evidence of increased CVD mortality in CRC, there remains a need for a comprehensive nationwide study.

Methods:
We utilized death certificates from the CDC WONDER (Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research) database from 1999 to 2020 to evaluate the trends of CVD-related mortality in CRC patients using ICD-10 codes. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and Annual Percentage Change (APCs) with 95% CI were stratified by year, sex, race/ethnicity, geographic region and place of death (POD).

Results:
Between 1999 and 2020, there were 1,304,077 deaths related to CRC in the United States. Of these, 414,367 (31.8%) deaths were related to CVD. The overall CRC + CVD related AAMR was 7.8 in 1999 and 4.6 in 2020 (Figure 1). The AAMRs of CRC + CVD deaths decreased at an APC of -3.69 (95%CI, -3.4 to -4.09) from 1999 to 2016; followed by an increase in AAMRs from 2016 to 2020 at an APC of 0.76 (95%CI, -1.29 to 5.4). Of the 387,618 CRC + CVD deaths with location available on POD, 153,114 (39.5%) occurred in medical facility, 128,728 (33.2%) in homes, 88,064 (22.7%) in nursing homes/long-term care and 17,712 (4.57%) in hospice facility. Males had higher overall AAMRs than females (7.1 vs. 4.6) which increased from 2016 to 2020 (APC 0.95); Black and African Americans had the highest AAMRs (7.8) which increased steadily by 5.1% from 2018 to 2020. Asian or Pacific Islander had the lowest AAMRs (3.9), however the rates increased by 4.4% in recent years between 2018 and 2020. Northeast region had the highest AAMR (6.7) while South had the lowest (5.0). The AAMRs was highest in rural (6.3) followed by urban (5.9), this gap widened in recent years as AAMR increased for rural (APC 1.7 from 2018 to 2020), while urban remained stable (APC -1.00 from 2016 to 2020).

Conclusion:
There has been a rising trend in CRC + CVD-related mortality in recent years despite an initial decrease for over a decade. Higher rates of hospital deaths and decreased usage of hospice facility was noted indicating lack of end-of-life-care. Significant demographic and geographic disparities exist amongst certain socioeconomic groups with increased mortality in recent years.
Abstract 4146129: Global, National and Regional Burden of Cardiovascular Disease in Women in 204 Countries and Territories and its Trend from 1990-2021: A Global Benchmarking Analysis.
Authors: Syed Saif , Bhalodia Paritaben , Katam Shruthi , dhillon nimrat , Shandilya Ashwinikumar , Ahmed Danish , Lakkimsetti Mohit , AMIN VISHRANT , Islam Rabia , Islam Hamza , DESAI HARDIK , sharma kamal , PATEL JUHI
Published: November 2024

Introduction:
Cardiovascular Disease (CVD) is the primary cause of death and disability among women worldwide. Despite its escalating impact, there remains a significant gap in consistent and comparative global data on the burden of CVD in women. This groundbreaking study provides the first estimates of the CVD burden in women over the past three decades, including the first two years of the COVID-19 pandemic.

Method:
Using the Global Burden of Disease 2021 framework, we estimated the prevalence, incidence, deaths, disability-adjusted life years (DALYs), and years lived with disability (YLDs) due to cardiovascular disease (CVD) in women. This analysis spans ages, years, and locations across 204 countries and territories from 1990 to 2021.

Results:
From 1990 to 2021, the total percentage change (TPC) in prevalence of the condition increased by 108%, followed by a 91% increase in incidence, and a 47% increase in deaths. Regionally, the highest TPC in age-standardized incidence rate (ASIR) was observed in Central Asia at 14%, while the highest mortality rate (ASMR) was in Southern Sub-Saharan Africa at 15%, and the highest YLD rate (ASYLDR) was in Australasia at 8% from 1990 to 2021. Nationally, Uzbekistan saw the largest increase in ASIR at 69%, and the United Arab Emirates had the highest increase in ASMR at 82%. In terms of socio-demographic index, the highest ASYLDR was observed in middle SDI regions with a 1% increase, while other regions saw decreases. Regarding age, individuals aged 55 and over recorded the highest deaths at 8.4 million, followed by the 20-54 age group with 659,296, and under 20s at 37,034 in 2021. Ischemic heart disease constituted 43.46% of all CVD-related deaths in 2021.

Conclusion:
Deaths due to cardiovascular disease (CVD) in women attributable to metabolic risk factors accounted for 70.75% of all CVD-related fatalities. This was followed by behavioral risk factors at 34.64% and environmental risk factors at 31.62%. The disproportionate impact of metabolic, behavioral, and environmental risk factors on cardiovascular disease-related deaths in women highlights the critical need for targeted intervention strategies. Addressing these risk factors through comprehensive public health initiatives could significantly reduce the global burden of CVD in women.
Abstract 4146133: The prognostic impact of energetic hemodynamics on acute heart failure
Authors: Sung Shih-Hsien , Tseng Chih-Hsueh
Published: November 2024

Background:
Central aortic hemodynamics significantly affect left ventricular function and clinical outcomes in patients with heart failure (HF). We proposed that energetic hemodynamic parameters could offer a more detailed understanding and a stronger correlation with left ventricular function and outcomes, compared to traditional pressure-based parameters.

Methods:
A total of 166 patients (61 years, 26.5% women) hospitalized due to HF (24% with preserved systolic function) were enrolled. Levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured at admission. At discharge, we assessed the augmentation index (AI), backward pressure (Pb) and carotid-femoral pulse wave velocity (cf-PWV) using tonometry, as well as aortic doppler flow. Energetic hemodynamic parameters were calculated by integrating pressure multiplied by flow over time.

Results:
While subjects with a left ventricular ejection fraction (LVEF) <50% exhibited significantly lower AI and Pb compared to those with LVEF of ≥50%, aortic and carotid energetic hemodynamic parameters were also significantly lower in patients with impaired LVEF. After adjusting for age, sex, estimated glomerular filtration rate, and NT-proBNP, the total and mean energy of the carotid artery were independently associated with mortality [hazard ratios and 95% confidence intervals: 1.009 (1.004-1.015) and 1.018 (1.006-1.026), respectively]. Subgroup analyses consistently demonstrated the prognostic value of energetic hemodynamics across different HF phenotypes.

Conclusion:
The study indicated that energetic hemodynamic parameters, especially the total and mean energy of the carotid artery, correlated with long-term survival, irrespective of LVEF. Notably, these energetic hemodynamics surpassed cf-PWV in their correlation with left ventricular systolic function.
Abstract 4146166: Effect of Sotagliflozin, a Dual SGLT1 and SGLT2 Inhibitor, on Systolic Blood Pressure in Patients with Type 2 Diabetes
Authors: Hardin Marquette , Davies Michael , Carroll Amy , Umpierrez Guillermo
Published: November 2024

Clinical trials (inTandem, SOLOIST-WHF, and SCORED) utilizing sotagliflozin (SOTA) have demonstrated glycemic improvements in patients with type 1 diabetes (T1D) and reduced heart failure (HF)-related events and cardiovascular (CV) mortality in patients with type 2 diabetes (T2D). SOTA has been evaluated for changes in cardiometabolic parameters including glycemia, blood pressure, and body weight in 8 double-blind, placebo (PBO)-controlled trials in patients with T2D. The glycemic efficacy of SGLTi including SOTA is attenuated with declining kidney function, but it is not known if the effects of SOTA on blood pressure are impacted as well.

The purpose of this post-hoc, patient-level meta-analysis from the Phase 3 studies in patients with T2D was to determine the effect of SOTA on systolic blood pressure (SBP) across a broad range of patients including those with moderate to severe renal impairment. The participants (mean age 63 yrs, BMI 32 kg/m
2
, SBP 133 mmHg, eGFR 74 mL/min/1.73m
2
) were treated with once-daily SOTA 400 mg (N=1728), SOTA 200 mg (N=728), or PBO (N=1440).

Of the 3,896 participants, there were 2,207 patients with a SBP≥ 130 mmHg and 1,120 with a SBP≥ 140 mmHg at baseline despite the use of antihypertensive medications in 81% of patients as well as 271 patients with eGFR < 30, 1,046 with eGFR 30 to < 60, and 2,577 with eGFR ≥ 60 mL/min/1.73m
2
. At 26 weeks, SOTA 200mg and 400mg significantly (p≤ 0.05) reduced SBP in all patients compared to PBO, LS mean difference (95% confidence interval [CI]) -3.5 (-4.7, -2.3) and -3.4 (-4.3, -2.5), respectively, as well as significant reductions in subgroups of patients with SBP≥ 130 mmHg, -2.6 (-4.3, -1.0) and -3.7 (-4.9,-2.5), respectively, and SBP≥ 140 mmHg, -2.5 (-4.9, -0.1) and -3.6 (-5.6, -1.7), respectively. Moreover, reductions in SBP with SOTA were seen in patients regardless of baseline eGFR. (Figure)

Despite the known attenuation of glycemic control with SGLTi with declining kidney function, the effects of SOTA on SBP are maintained in patients with T2D regardless of kidney function. Together with improvements in other cardiometabolic parameters shown in both patients with T1D and T2D, SOTA may offer a new therapeutic option for patients with diabetes.
Abstract 4146171: LDL-C Lowering with Evolocumab and Arterial Aneurysms: Long-Term Analysis from the FOURIER Trial
Authors: Gaba Prakriti , Zimerman Andre , O'Donoghue Michelle , Giugliano Robert , Murphy Sabina , Kuder Julia , Monsalvo Maria Laura , Flores-Arredondo Jose , Atar Dan , Keech Anthony , Sabatine Marc , Marston Nicholas , Bergmark Brian
Published: November 2024

Introduction:
Arterial aneurysms, particularly abdominal aortic aneurysms (AAA), are life-threatening conditions. Human genetic studies and preclinical mouse models have supported LDL-C reduction through PCSK9i as a strategy to slow the progression of arterial aneurysms.

Aims:
To investigate the rates of arterial aneurysm events among patients randomized to the PCSK9i evolocumab vs. placebo.

Methods:
In FOURIER, 27,564 patients with stable ASCVD and LDL-C ≥70 or non-HDL-C ≥100 mg/dL on statins were randomized to evolocumab vs. placebo and followed for a median of 2.2 years. 6,635 patients entered the open-label extension period and received evolocumab for 5 years, irrespective of initial assignment. The primary endpoint of this analysis was any aneurysm event, defined as diagnosis, progression, or intervention related to an arterial aneurysm. Adverse events were reported by the local site and potential aneurysm events were centrally identified by blinded investigators. Procedure-related pseudoaneurysms were excluded. A Cox model, adjusted for randomization stratification factors and an indicator for inclusion in the open-label cohort, was used to compare randomized groups throughout the two trial periods.

Results:
A total of 236 patients had aneurysm events (58% AAA) during follow-up. Patients who had aneurysm events were older (median age 67 vs. 63 yrs), more likely to be male (86% vs. 75%) and have a history of PAD (21% vs. 13%). Patients randomized to evolocumab had significantly lower rates of aneurysm events during follow-up (HR 0.77 [0.59–0.99]; p=0.041) (
Figure
). The association between randomization to evolocumab and fewer aneurysm events was consistent for both AAA (HR 0.78 [0.56–1.09]) and non-AAA (HR 0.81 [0.55–1.18]).

Conclusion:
In patients with stable ASCVD on optimized statin therapy, early initiation of long-term evolocumab was associated with fewer arterial aneurysm events compared with delayed initiation. These data support earlier intensive LDL-C reduction with PCSK9i as a promising strategy to prevent the formation and progression of arterial aneurysms, including AAA.
Abstract 4146203: Ultrasound-Targeted Microbubble Cavitation For The Treatment Of Myocardial Microvascular Obstruction: A Porcine Study
Authors: Amjad Muhammad Wahab , Mohammed Soheb Anwar , Chen Xucai , Villanueva Flordeliza , Pacella John
Published: November 2024

Introduction:
In 2019, 17.9 million people died from cardiovascular disease, 85% of which were due to acute myocardial infarction (AMI). Post-AMI congestive heart failure is increasing due to microvascular obstruction (MVO). MVO is the blockage of the microcirculation by atherothrombotic debris and tends to occur after coronary stenting for AMI. Current therapeutic strategies for MVO are not consistently effective.

Aim:
Our goal is to develop ultrasound (US)-targeted microbubble cavitation (UTMC) as a potential treatment for MVO.

Methods:
Initially, we demonstrated the efficacy of UTMC in a rat hindlimb model of MVO. Given these promising findings, in the current work, we expanded our investigation to a clinically relevant porcine model of myocardial MVO. On day 1, MVO was created in the left anterior descending (LAD) microcirculation and confirmed by myocardial contrast echocardiography (MCE). The MVO in the LAD bed was then treated with UTMC therapy during concurrent infusion of Definity
®
contrast agent. The therapeutic ultrasound (1.3 MHz center frequency, 1.3 MPa peak negative pressure, 1 ms pulse duration) was delivered with Philips EpiQ (with S5-1 probe). Cardiac MRI was obtained at 36 hours to measure infarct size and area of MVO. At 48 hours post UTMC therapy, MCE was repeated, and the animals were euthanized. Hearts were stained with Evans Blue/ TTC dyes and sectioned for analysis of infarct size. A total of 11 pigs, 5 Control (MVO, no treatment) and 6 UTMC (MVO, UTMC treatment) were done.

Results:
LAD angiographic flow was improved at 48 hours post UTMC treatment in comparison to control. MCE imaging revealed that the UTMC treatment significantly improved LV systolic performance, and LAD blood volume (Figure 1), as compared to control. MRI clips showed that UTMC ameliorated MVO and left ventricular (LV) segmental wall motion and ejection fraction (EF) also improved after UTMC treatment versus control. Infarct size was reduced as shown by both Evans Blue/TTC staining and MRI.

Conclusions:
Taken together, we demonstrated that UTMC significantly reduced infarct size, enhanced LAD microvascular perfusion and improved LV systolic performance, and should enable clinical translation of this promising therapy.
Abstract 4146205: Housing Status Disparities in Inpatient Outcomes of Chronic Limb-Threatening Ischemia
Authors: Millhuff Alexandra , Quazi Mohammed , Goyal Aman , Sheikh Abu Baker
Published: November 2024

Introduction:
Chronic limb-threatening ischemia (CLTI) is associated with significant morbidity and mortality, and has a high risk of limb amputation. Previous studies have found gender and racial disparities with regards to mortality and disease severity, but the impact of other social factors such as housing status has yet to be investigated. Identifying potential disparities is key to developing targeted interventions to address inequities in social determinants of health.

Research Question:
What impact does housing status have on inpatient outcomes of limb-threatening ischemia?

Methods:
A retrospective analysis using the National Inpatient Sample database from 2016-2021 was carried out to identify patients admitted with CLTI who underwent revascularization, identified by ICD-10 codes. Patients were stratified by their housing status. A propensity-matched analysis was subsequently performed to compare demographics, comorbidities, mortality rates, types of intervention, and inpatient outcomes between patients with stable versus unstable housing.

Results:
2,667,294 patients were identified who were admitted with a primary diagnosis of CLTI, and 463,435 (17%) underwent revascularization. Among these, 1,790 (0.4%) of patients were identified as unhoused. Patients who were unhoused were less likely to undergo open surgical intervention (aOR 0.40, CI 0.32-0.50, p=<0.001) or endovascular revascularization (aOR 0.51, CI 0.43-0.61, p<0.001). Unhoused patients had longer hospital stays (4 days longer, p<0.001), and more expensive inflation-adjusted hospital costs ($8,501 higher, p<0.001), compared to housed patients. Unhoused patients were more likely to leave against medical advice and be discharged to skilled nursing facilities rather than home. Unhoused patients also had higher rates of smoking and polysubstance use. Mortality rates were similar between housed and unhoused patients.

Conclusion:
Housing status has a significant role on interventions offered and inpatient outcomes of CLTI patients. Additional research is required to understand disparities in interventions for unhoused CTLI patients. Understanding heightened risk factors for the development of CLTI in unhoused populations is key to addressing disease morbidity in these groups.
Abstract 4146208: Blood protein mediators of association between smoking and abdominal aortic aneurysm: exploration integrating human proteomic and genomic data
Authors: Yuan Shuai , Khodursky Samuel , Geng Jiawei , Sharma Pranav , Spin Joshua , Tsao Philip , Levin Michael , Damrauer Scott
Published: November 2024

Background:
Cigarette smoking has been identified as an important risk factor for the development of abdominal aortic aneurysm (AAA) and is known to influence levels of blood proteins. However, protein mediators of the smoking-AAA link remain unexplored. Here, we conducted a two-stage Mendelian randomization (MR) study to comprehensively pinpoint possible protein mediators by leveraging large-scale proteomic and genomic data.

Methods:
We first assessed the associations between genetically predicted smoking traits (lifetime smoking index, smoking initiation and cigarettes per day) and AAA risk (β
total
). We then performed a protein-wide MR analysis to explore circulating proteins associated with smoking traits (β
1
). Among identified proteins, we established their levels associated with AAA risk (β
2
). According to directionality (β
total
vs. β
1
×β
2
), pathways were constructed, and corresponding mediation proportions were estimated by (β
1
× β
2
)/ β
total
×100%. Genetic instruments for smoking traits were selected by filtering variants at
P
< 5×10
-8
and

r
2

<0.001.
Cis
variants from encoding gene region ± 1Mb were used as instruments for protein. Summary level data on proteins and AAA were obtained from the deCODE study (N=35,559), Fenland study (N=10,708), and AAAgen consortium (37,214 cases), respectively. MR associations were estimated by the multiplicative random effects inverse variance method and summary-data-based MR method were applicable. We performed colocalization analysis for protein-AAA associations. Multiple testing was controlled with False Discovery Rate.

Results:
Genetically predicted smoking traits were associated with an increased genetic liability to AAA and genetically predicted levels of 48 proteins. Among 48 smoking-associated proteins, genetically predicted levels of 9 proteins were associated with genetic liability to AAA. Three protein pathways were established. Specifically, genetically predicted levels of WFDC2, MMP12, and SMPD1 mediated approximately 10.0 (1.4-18.6) %, 3.6 (1.7-5.5) %, and 2.2 (95% 0.7-3.7) % of the association between genetically predicted lifetime smoking index and genetic liability to AAA. Colocalization evidence was only observed for the SMPD1-AAA association (PH4=0.98).

Conclusions:
The study revealed a wide effect of cigarette smoking on blood proteins and suggested three potential pathways linking smoking and AAA, including MMP12 which has long been appreciated as important to AAA formation in model systems.
Abstract 4146209: Comparative Efficacy and Safety of Colchicine and Anti-Interleukin-1 Agents in Recurrent Pericarditis: A Pairwise and Network Meta-analysis of Randomized Controlled Trials
Authors: Ehsan Muhammad , Syed Alveena , Mustafa Biah , Khan Muhammad Hammad , Klein Allan
Published: November 2024

Background:
The management of recurrent pericarditis has evolved to include colchicine and novel anti-interleukin-1 agents, given the limited efficacy of traditional NSAIDs and corticosteroids. We conducted a pairwise and network meta-analysis to evaluate the efficacy and safety of colchicine and anti-IL-1 agents in recurrent pericarditis.

Methods:
We conducted a comprehensive search on various databases and registries, such as MEDLINE (via PubMed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), to retrieve relevant RCTs. We used STATA version 17 to perform meta-analyses under a random-effects model and applied the empirical Bayes (Paule and Mandel) variance estimator to dichotomous data. We performed a network meta-analysis with a placebo/standard therapy group as the comparator in MetaXL 5.3 using the Generalized Pairwise Modeling based on the Bucher method.

Results:
A total of 6 RCTs were included in the meta-analysis. The risk of pericarditis recurrence was significantly decreased by colchicine (RR 0.46, 95% CI 0.37-0.58) and anti-IL-1 agents (RR 0.13, 95% CI 0.03-0.54) compared to placebo or standard therapy. Colchicine significantly decreased the risk of treatment failure (RR 0.42, 95% CI 0.31-0.57) but did not have a significant impact on the risk of adverse events (RR 1.06, 95% CI 0.31-3.62). No significant risk of adverse events (RR 2.16, 95% CI 0.66-7.01) or serious adverse events (RR 1.01, 95% CI 0.23-4.41) was observed with anti-interleukin-1 agents. Colchicine was also associated with a decreased risk of pericarditis-related rehospitalization (RR 0.26, 95% CI 0.10-0.70). The network meta-analysis showed that anti-IL-1 agents (RR 0.13, 95% CI 0.05 to 0.30) were associated with a greater reduction in pericarditis recurrence than colchicine (RR 0.46, 95% CI 0.37 to 0.59). All anti-interleukin-1 agents significantly decreased the risk of pericarditis recurrence, with comparable efficacies among the different agents.

Conclusion:
Colchicine and anti-IL-1 agents significantly reduced the risk of pericarditis recurrence with the anti-IL-1 agents demonstrating greater efficacy. Further, high-powered, large-scale RCTs that directly compare various treatment options are needed to confirm or refute our findings.
Abstract 4146210: TCF7L2 Deficiency in Vascular Smooth Muscle Cells Mitigates Abdominal Aortic Aneurysm
Authors: Deng Yongjie , Zhao Yang , Lu Haocheng , Zhao Guizhen , Liu Hongyu , Chen Y. Eugene , Zhang Jifeng
Published: November 2024

Introduction:
Abdominal aortic aneurysm (AAA) is a major cardiovascular disease characterized by the dysregulation of vascular smooth muscle cell (VSMC) homeostasis. TCF7L2, a transcription factor involved in Wnt signaling, plays a key role in cell proliferation and differentiation. Genome-wide association studies (GWAS) have identified the gene as being positively associated with aortic aneurysms, but its specific impact and the underlying mechanisms on AAA remain unclear.

Methods and Results:
Two models were employed to induce AAA in VSMC-specific
Tcf7l2
knockout (floxed
Tcf7l2
/
Myh11
-CreERT2) mice: elastase- and AngII/BAPN-induced AAA models. TCF7L2 deficiency in VSMCs significantly alleviated AAA formation, aorta dilation, elastin degradation, and VSMC apoptosis in both models. In primary human aortic smooth muscle cells, small interfering RNA-mediated Tcf7l2 knockdown attenuated glycolysis and lactate production, as revealed by RNA sequencing, targeted metabolomics, lactate assay, and Seahorse Glycolysis Stress Test. TCF7L2 deficiency in VSMCs also inhibited cell migration, TNFα/CHX- and FasL-induced apoptosis. Conversely, adenovirus-mediated overexpression of TCF7L2 promoted these processes. We further performed Cut&Run sequencing and ChIP sequencing analysis, the data revealed that TCF7L2 binds to the promoter regions of Ldha/b and Tp53 genes, indicating that TCF7L2 promotes VSMC glycolysis and apoptosis through direct interaction with these key genes. Additionally, TCF7L2 upregulated the mRNA and protein expression of MMP14 in VSMCs, suggesting a mechanism by which TCF7L2 regulates extracellular matrix organization.

Conclusions:
Our data indicate that TCF7L2 plays a key role in AAA development by modulating VSMC glycolysis, apoptosis, migration, and extracellular matrix organization, highlighting TCF7L2 as a potential target for treating VSMC-related diseases.