bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4124226: Long-term exposure to air pollutants and incidence of cardiovascular disease events and mortality in The Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air)
Authors: Young Michael T , Barr R. Graham , Bertoni Alain , Daviglus Martha , Diez Roux Ana , Jacobs David , Kronmal Richard , Navas-Acien Ana , Post Wendy , Sheppard Lianne , Siscovick David , Szpiro Adam , WATSON KAROL , Kaufman Joel
Published: November 2024

Introduction:
Exposure to ambient air pollution may increase the risk of cardiovascular disease events and mortality, but prior publications have primarily included administrative cohorts with outcomes that have not been individually reviewed and with air pollution estimates created without cohort-specific exposure monitoring. Multi-Ethnic Study of Atherosclerosis (MESA) is a multi-site cohort study designed specifically to prospectively collect and adjudicate cardiovascular disease (CVD) events. MESA Air recruited additional participants into sub-cohorts for enhanced air pollution variation and sample size.

Research Question:
The aim of this analysis was to characterize the relationship between long-term exposure to nitrogen dioxide (NO
2
) and fine particulate matter (PM
2.5
) and all-cause mortality and CVD events.

Methods:
Air pollution exposure was assessed using address history with a purpose-built exposure model incorporating cohort-specific monitoring including measurement and validation at participant homes. We used Cox models to assess the risk of rolling 2-year average exposures on all cause-mortality and on a composite CVD endpoint (definite angina, probable angina with revascularization, myocardial infarction, atherosclerosis or other CVD death, resuscitated cardiac arrest, and stroke). Models were stratified for baseline hazard by age, sub-cohort, and recruitment year and were additionally adjusted for age, sex, race/ethnicity, field center, smoking/second-hand smoke, pack-years, physical activity, education, income, neighborhood socioeconomic status, and statin use.

Results:
MESA Air participants were aged 44-87 years at enrollment between 2000 and 2007; follow-up averaged 14 years. 6,915 participants had follow-up for events, NO
2
exposure, and covariate information. We observed 1,442 deaths and 985 CVD events. The interquartile range over all 2-year averages was 10.5-23.1 ppb for NO
2
and 10.1-14.9 µ/m
3
for PM
2.5
. The adjusted hazard ratio (aHR) for a 10 ppb increment in NO
2
was 1.38 (95% CI: 1.17, 1.64) for all-cause mortality and 1.16 (95% CI: 0.95, 1.42) for incident CVD events. The aHR for a 5 µg/m
3
increment in PM
2.5
was 1.20 (95% CI: 0.99, 1.46) for all-cause mortality and 1.15 (95% CI: 0.95, 1.39) for incident CVD events

Conclusions:
These results add to growing literature demonstrating an association between air pollution exposure, mortality, and CVD in a cohort with well-characterized clinical endpoints and cohort-specific exposure assessment.
Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial
Authors: Haller Paul , Marston Nicholas , Bellavia Andrea , Jarolim Petr , Keech Anthony , Giugliano Robert , Sabatine Marc , Morrow David
Published: November 2024

Background:
Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting.

Aims:
To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events.

Methods:
We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL
>
70 or non-HDL
>
100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI
BL
and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks.

Results:
Median age was 63 yrs (25
th
, 75
th
percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI > LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5
th
, 25
th
, 75
th
, 95
th
percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI
BL
and depending on absolute hs-cTnI change to 24 wks is shown in
Fig. A
. Higher Hs-cTnI
BL
was associated with higher event rates (p < 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI
BL
. Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect < 0.001,
Fig. B
).

Conclusion:
Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.
Abstract 4124335: Ticagrelor monotherapy the way forward after Percutaneous Coronary Interventions : An updated meta-analysis
Authors: Mansuri Zeeshan , Ashraf Hadiah , Taikadan Thahsin , Rajith Gokul , Ayesha Ayesha , Fatima Urooj , Erzinger Gabriel
Published: November 2024

Background:
With the advent of newer generation drug eluting stents, the chorus for shortening the duration of dual antiplatelet therapy (DAPT) after percutaneous coronary interventions (PCI) is getting louder and louder. Ticagrelor monotherapy after a short course of DAPT has been studied in a few randomized controlled trials with promising results. We conducted a systematic review and meta-analysis comparing the ticagrelor monotherapy with DAPT after short duration DAPT in patients undergoing PCIs.

Methods:
PubMed, Embase and Cochrane databases were searched for RCTs comparing ticagrelor monotherapy to DAPT after PCI and reported the outcomes of Major Adverse Cardiac Events including death, myocardial infarction or stroke (MACE); Major Adverse Cardiac and Cerebrovascular Events including death, myocardial infarction, stroke, stent thrombosis or target vessel revascularization (MACCE); Major bleeding; Death from any cause; CV death; Stent thrombosis and Target vessel revascularization (TVR). Data were extracted from published reports and quality assessment was performed per Cochrane recommendations. Statistical analysis was performed using Review Manager Web (Cochrane Collaboration). Heterogeneity was examined with I
2
test.

Results:
Out of 3208 database results, 5 RCTs with 32,393 patients were included; 16,188 (50%) received Ticagrelor monotherapy. Studies had mean follow-up ranging from 12 months to 24 months. Baseline characteristics are as per Table 1. Safety endpoints of major bleeding (HR 0.50; 95% CI 0.38-0.66; p < 0.0001; I
2
= 23 %; Figure 1A), was significantly less with ticagrelor monotherapy. Efficacy endpoints of MACE, MACCE, Death from any cause, CV Death, target vessel revascularization (TVR) and stent thrombosis were not significantly different between ticagrelor and DAPT (Figure 1 and 2).

Conclusion:
Ticagrelor monotherapy reduces major bleeding as compared to continued DAPT for 12 months after PCI. Major ischemic outcomes were similar in both groups. Ticagrelor monotherapy may be the way forward after short duration of DAPT in patients undergoing PCI.
Abstract 4124342: Invasive CPET-based hemodynamic correlates of abnormal peak VO
2
and V
E
/VCO
2
in HFpEF and pre-capillary Pulmonary Hypertension
Authors: ElShaer Ahmed , Abed Anas , Tu Wanxin , Jan Justin , Cochrane Margaret , Garcia-Arango Mariana , Kenarsary Aria , Gallegos Arthur , Abdul wahab arif , Tehrani Babak , Runo James , Raza Farhan
Published: November 2024

Introduction:
Pulmonary hypertension (PH) is a heterogeneous disease characterized by impaired gas exchange (CO
2
, O
2
) in the pulmonary circulation, leading to dyspnea and exercise intolerance. We hypothesize that specific hemodynamic metrics correlate with poor gas exchange in PH phenotypes, which can be leveraged to define therapeutically relevant hemodynamic targets.

Aim:
This study aims to define hemodynamic correlates of poor gas exchange (peak VO
2
, V
E
/VCO
2
slope) in heart failure with preserved ejection fraction (HFpEF) and pre-capillary PH.

Methods:
We retrospectively analyzed 170 participants with invasive cardiopulmonary exercise testing: HFpEF (n=91), pre-capillary PH (n=54), and non-cardiac dyspnea (NCD, n=25). Linear regression models, adjusted for patient groups with interaction, were used to assess the association of peak VO
2
and V
E
/VCO
2
slope with predictors (pulmonary vascular resistance [PVR], distensibility, and pulmonary arterial compliance [PAC]).

Results:
In the order of NCD vs. HFpEF vs. pre-capillary PH, rest PAC (5.5±1.6 vs 3.8±1.7 vs 2.6±1.3 mL/mmHg), rest PVR (1.4±0.6 vs 3.2±2.0 vs 5.7±3.0 Woods unit), and distensibility (1.5±0.5 vs 0.8±0.4 vs 0.5±0.2 % per mmHg). In comparison to a non-significant correlation with rest PVR and distensibility, peak VO
2
(%predicted) showed significant correlation with rest PAC (p<0.01) with significantly positive slope of +6 in HFpEF and +10 in pre-capillary PH. Similarly, significant slopes were noted with rest PAC and V
E
/VCO
2
relationship (p<0.01) in HFpEF (-3) and pre-capillary PH (-4).

Conclusion:
Pulmonary arterial compliance (PAC) is the best correlate of poor gas exchange. Improving rest PAC by 1.0 mL/mmHg can lead to improvement in peak VO
2
predicted (+10% in pre-capillary PH, +6% in HFpEF), and V
E
/VCO
2
slope (-4 in pre-capillary PH, and -3 in HFpEF). In comparison to pre-capillary PH, more limited improvement in HFpEF is likely due to multi-organ dysfunction leading to exercise intolerance.
Abstract 4124369: Mid-term Outcomes of Transcatheter Versus Surgical Aortic Valve Replacement in Low to Moderate Risk Patients with Severe Aortic Stenosis: A Meta-analysis of Randomised Clinical Trials
Authors: Pascoal Capela , Saugo Faria Hilária , Peres Clara , Francisco Antonino , Tavares Luiz Fernando , Doma Mohamed , Bombassaro Masiero Barbara , Manuel Valdano
Published: November 2024

Background:
Several clinical trials have demonstrated non-inferiority of transcatheter aortic valve replacement (TAVR) compared with surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) and low to intermediate surgical risk. However, mid-term results are still contentious.

Question:
Is TAVR superior to SAVR in the mid-term in terms of mortality outcomes or adverse cardiovascular events?

Methods:
We searched Embase, Pubmed and Cochrane databases for RCTs that compared TAVR with SAVR in patients with symptomatic severe AS with a follow-up of at least 4 years. Outcomes of interest were all-cause mortality and disabling stroke.

Results:
We included six RCTs involving 6,444 patients with severe AS, of whom 3,282 (50.9%) underwent TAVR. There was no difference in mortality from all causes (RR 1.08; 95%CI 0.94-1.25; p=0.30; I
2
=45%) and disabling stroke (RR 0.95; 95%CI 0.75-1.21; p=0.67; I
2
=9%) between groups. In the subgroup analysis, 5-year mortality (RR 1.28; 95%CI 1.10-1.49; I
2
=0%) was higher in the TAVI group. The new pacemaker implantation rate was higher in the TAVI group (RR 2.22; 95%CI 1.42-3.45; p=0.0004 ; I
2
=91%). However, new atrial fibrillation rate was higher in the SAVR group (RR 0.42; 95%CI 0.37-0.49; p=0.00001; I
2
=62%).

Conclusion:
Mid-term mortality and disabling stroke of patients with severe AS treated with TAVR or SAVR were similar.
Abstract 4124677: Left ventricular function and myocardial longitudinal strain analysis in patients with Chagas disease: case series and systematic literature review.
Authors: da Nóbrega Borges José Victor , Leila Samira , Machado Manuella
Published: November 2024

Introduction:
Chagas disease is a significant cause of tropical disease-related mortality. It presents in acute, indeterminate, and chronic phases, with chronic cardiomyopathy being the most severe form, leading to heart failure, arrhythmias, and sudden cardiac death. Conventional echocardiography often fails to detect early subclinical dysfunction, whereas Global longitudinal strain (GLS) may provide earlier detection of myocardial strain abnormalities. Left ventricular dysfunction is an independent predictor of mortality and GLS is an emerging modality that may aid early detection of cardiac involvement.

Objective:
This study aims to compare left ventricular function using multiple echocardiographic parameters between patients with indeterminate and chronic forms of Chagas disease and to perform a systematic literature review.

Methods:
The observational study involved 11 patients (mean age 76.36 years) from a tertiary hospital in Brazil, classified as indeterminate (45%) or chronic (55%). Serological confirmation and detailed echocardiographic evaluations, including GLS, were performed. A systematic literature review was also conducted on GLS in Chagas cardiomyopathy.

Results:
Patients with chronic Chagas disease showed significantly lower LVEF and GLS compared to those with the indeterminate form. Segmental strain analysis revealed consistent contractility reductions across specific ventricular segments in both groups.

Discussion:
Chagas cardiomyopathy often leads to dilated cardiomyopathy with significant arrhythmias and heart failure. GLS can detect early myocardial changes even before a significant drop in LVEF, indicating its potential for early diagnosis and better management of Chagas cardiomyopathy. Literature review supports the use of GLS for detecting early cardiac involvement and predicting adverse outcomes.

Conclusion:
Incorporating GLS with conventional echocardiography offers enhanced early detection of myocardial changes in Chagas disease. While promising, further research is needed to establish the clinical significance and impact of these techniques in routine practice.
Abstract 4124709: Accelerometer-Measured Sedentary Behavior and Future Cardiovascular Disease
Authors: Ajufo Ezimamaka , Kany Shinwan , Ramo Joel , Churchill Timothy , Guseh James , Aragam Krishna , Ellinor Patrick , Khurshid Shaan
Published: November 2024

Background:
Current consensus guidelines emphasize the importance of achieving 150 minutes or more of moderate to vigorous physical activity (MVPA) per week to promote cardiovascular health but give little guidance about sedentary behavior.

Research Question:
Is sedentary behavior associated with cardiovascular (CV) disease in a manner distinct from insufficient physical activity?

Aims:
Examine associations between accelerometer-measured sedentary behavior with risk of specific CV outcomes, including potential interactions with MVPA.

Methods:
Using 89,530 individuals providing one week of accelerometer-based physical activity data from the UK Biobank, we fit Cox models adjusted for demographic and lifestyle factors to assess associations between sedentary time (as a spline term) and incident atrial fibrillation (AF), myocardial infarction (MI), heart failure (HF), and CV mortality. We assessed the potential effect of MVPA on these associations by including MVPA as an adjustment variable, as well as performing subgroup analyses stratified at the guideline-recommended MVPA threshold.

Results:
Among 89,530 individuals (age 62±8 years, 56.4% women) undergoing accelerometry, median sedentary time was 9.4 hours/day (quartile-1: 8.2, quartile-3: 10.6). In multivariable models, using the second quartile (8.2-9.4 hours/day) as a referent, sedentary time in the top quartile (>10.6 hours/day) was associated with greater risk of HF (hazard ratio [HR] 1.45, 95% CI 1.28-1.65), and CV mortality (HR 1.62, 95% CI 1.34-1.96), with evidence of a threshold effect at 10.6 hours/day. Higher sedentary time was also associated with greater risk of incident AF (HR 1.11, 95% CI 1.01-1.21) and MI (HR 1.15, 95% CI 1.00-1.32), with an approximately linear relation. Associations with HF and CV mortality persisted after adjustment for MVPA, as well as among individuals both above and below the guideline-based activity threshold of ≥150 minutes MVPA/week.

Conclusions and Relevance:
Sedentary behavior is broadly associated with future adverse CV outcomes. For HF and CV mortality, associations appear distinct from insufficient MVPA, and sedentary time in excess of 10.6 hours/day conferred an increased risk.
Abstract 4124722: Cardiac imaging-pathology correlation in 283 pediatric heart transplant biopsy specimens: Cardiac MRI detects clinically important fibrosis
Authors: Gupta Aditi , ceneri nicolle , Mouzakis Nick , Richmann Devika , Kanter Joshua , Downing Tacy , Vegulla Ravi , Rossi Christopher , Berger John , Cross Russell , Olivieri Laura
Published: November 2024

Background:
Cardiovascular magnetic resonance (CMR) derived T1 parametric mapping offers quantitative, regional assessments of myocardial edema and fibrosis. Pediatric cardiac allografts are subject to fibrosis due to rejection inflammation, coronary vasculopathy, cardiopulmonary bypass and graft failure. The role of CMR parametric mapping in identifying clinically important myocardial fibrosis in this population remains unknown. Thus, the aim of this study was to correlate endomyocardial biopsy (EMB)-derived fibrosis measurements with local T1 values in PHTx patients.

Methods:
PHTx pts undergoing EMB also underwent simultaneous cardiac MRI including T1 parametric mapping in 6 short axis slices at 1.5 T. Segmental T1 values were measured and the segments corresponding to EMB sites were noted from overlay registration. Trichrome-stained EMBs were digitally scanned and analyzed for fibrosis content. Encounters were divided into low and high fibrosis groups, and clinical variables from echocardiography, clinical treatment, and cardiac catheterization were compared using student’s t-test and linear regression.

Results:
Thirty-three PHTx pts (age of 12.8
+
4.9 years) underwent 94 surveillance encounters, for a total of 283 EMB samples. 75 encounters had no active rejection and 19 encounters had active rejection requiring treatment. Average T1 was significantly higher in active rejection group (1056 vs 1018 ms, p<0.01), and there was no difference in fibrosis score between the 2 groups, thus identifying rejection as the main driver of T1 elevation. In the group with no active rejection, the T1 value from the EMB site was elevated in the high fibrosis score group (1023 vs 1011 ms, p=0.01). Of these patients without rejection, the higher fibrosis group had higher BNP (626 vs 145, p=0.04), higher lateral mitral E/e’ (8 vs 6.6, p=0.03) and higher RVEDP (11 vs 9 mmHg, p=0.05), all suggestive of more significant diastolic dysfunction.

Conclusions:
CMR derived segmental T1 value can detect clinically significant graft rejection. In the absence of rejection, elevated T1 correlates with clinically significant fibrosis on EMB, which correlates with markers of diastolic dysfunction.
Abstract 4124769: Temporal Changes in Clinical Characteristics and Oucomes of Infective Endcarditis: A Report from JROAD-DPC Study
Authors: Uemura Shiro , Okamoto Hiroshi , Nishi Takeshi , Kanaoka Koshiro , Iwanaga Yoshitaka , Izumi Chisato
Published: November 2024

Background:
Despite advances in medical science and patient care, infective endocarditis (IE) is still a serious and life-threatening disease. Considering the recent shifts in predisposing clinical backgrounds of cardiovascular disease, such as an aging population and increased usage of prosthetic valves and cardiovascular implantable electronic devices, ongoing updates to patient characteristics and outcomes of infective endocarditis (IE) are essential for providing precision diagnoses and effective treatments.

Objective:
To examine temporal trends in the clinical characteristics and in-hospital occurrence of adverse outcomes of IE.

Methods:
Observational study of using a nationwide Japanese administrative database (JROAD-DPC), that is operated by the Japanese Circulation Society. IE was identified based on the code of the International Classification of Diseases, Tenth Revision. The study outcomes were in-hospital mortality and IE-compatible complications (heart failure, cerebrovascular episodes, renal failure, and sepsis).

Results:
Between the years 2016 and 2021, a total of 17,407 IE patients (37.8% female; median age 72 (IQR, 59-81) years) were identified in JROAD-DPC database. The incidence of IE increased from 2.02 per 100,000 population (2,534 cases) in 2016 to 2.59 (3,183 cases) in 2021. The median age of the patients increased from 70 years in 2016 to 73 years in 2021, and patient backgrounds were becoming more complex. Notably, the proportion of patients older than 80 years rose from 25.4% to 30.8%. The in-hospital mortality rate was 14.5%, which significantly increased from 14.1% in 2016 to 15.4% in 2021. Higher age (OR, 1.34; 95% CI, 1.29 to 1.40; <.001), heart failure (OR, 1.37; 95% CI, 1.18 to 1.59; P<.001), cerebrovascular complications (OR, 1.78; 95% CI, 1.59 to 1.99; P<.001), renal failure (OR, 2.36; 95% CI, 2.06 to 2.70; P<.001), and sepsis (OR, 2.79; 95% CI, 2.48 to 3.13; P<.001), were independently associated with increased in-hospital mortality. In contrast, cardiac surgery (OR, 0.47; 95% CI, 0.41 to 0.55; P<.001), and a higher number of total cardiac surgeries (OR, 0.77; 95% CI, 0.65 to 0.92; P<.004) independently predicted a lower in-hospital mortality.

Conclusions:
The characterization and comprehensive analysis of IE in Japan provide valuable insights into the epidemiology, risk factors, and outcomes of IE, which may inform health service planning and treatment strategies.
Abstract 4125025: Association between Marital Status and Major Adverse Cardiovascular Events: Role of Stress-Related Neural-Immune Mechanisms
Authors: LAU HUI CHONG , Abohashem Shady , AbiKaram Krystel , Civieri Giovanni , Assefa Alula , Hanlon Erin , Qamar Iqra , Khalil Maria , Aldosoky Wesam , Seligowski Antonia , Osborne Michael , Tawakol Ahmed
Published: November 2024

Background:
Chronic stress is associated with cardiovascular disease (CVD) in part through neural mechanisms that potentiate inflammation. Disrupted social connections are associated with higher chronic stress. As such, we hypothesized that: 1) previously married (divorced, separated) individuals have higher major adverse cardiovascular event (MACE) risk compared to married individuals and 2) that greater activation of stress-related neural-immune mechanisms contributes to this relationship.

Methods:
Participants (N=75,638) enrolled in the Mass General Brigham Biobank were studied. Marital status and MACE were identified using survey data and ICD-10 codes, respectively. A subset (N=1,121) underwent clinical
18
F-FDG-PET imaging, enabling assessment of stress-related neural activity as the ratio of the amygdala to prefrontal cortex activity (AmygAc). Clinical high-sensitivity C-reactive protein (hs-CRP) levels were assessed in another subset of the cohort (N=10,358). Linear and Cox regression and mediation analyses were used.

Results:
Among participants (median age 62 years; 53% female), 2,978 subjects developed MACE after Biobank enrollment. Previously married (vs. currently married) individuals had greater MACE risk (HR 1.33 [95% CI: 1.20,1.57], p=<0.001,
Figure 1A
) , higher AmygAc (B=0.23 [95% CI: 0.06-0.40], p=0.009) and higher hs-CRP (B=0.19 [95% CI: 0.13-0.25], p=<0.001). MACE risk remained significant after adjustment for key confounders (
Table 1
), and both the AmygAc and CRP were higher among divorced or separated individuals (
Figure 1B and 1C
). Moreover, increased AmygAc and hs-CRP associated with increased MACE risk (HR=1.24 [1.14-1.36], p=<0.001 and 1.13 [1.09-1.16], p=<0.001, respectively), and both AmygAc and hs-CRP mediated the relationship between marital status and MACE (p<0.05).

Conclusions:
Our findings suggest that divorced and separated individuals are at an increased risk for MACE. This relationship appears to be driven in part by stress-related neural-immune mechanisms.
Abstract 4125093: Association of Systemic Inflammatory Index and Systemic Inflammatory Response Index with Major Adverse Cardiovascular Events in Patients with Acute Coronary Syndrome Who Had Primary Percutaneous Coronary Intervention
Authors: Alshraideh Jafar , Al-Hawamdeh Nemeh , Alkanash Heba
Published: November 2024

Introduction:
Inflammation plays an important role in the pathogenesis of coronary artery disease and Acute Coronary Syndrome (ACS). Inflammatory indicators such as neutrophil count and monocyte count potentially may predict patients’ outcomes and prognosis in ACS. White blood cells count is an affordable and accessible way to assess the systemic immune response. Considering their multidirectional effect on atherosclerosis, new inflammatory biomarkers integrating various leukocyte subgroups have been proposed to calculate the systemic inflammatory response index (SIRI) and systemic inflammatory index (SII).

Aim:
The aim of this study was to assess the association between the systemic inflammatory response index (SIRI) and Systemic inflammatory index (SII) at admission with major adverse cardiovascular events (MACE) 30-days after Primary Percutaneous Coronary Intervention (PPCI) among patients with Acute Coronary Syndrome (ACS) at one referral hospital in Jordan.

Method:
A Prospective design was used to assess and follow 150 adults presented with ACS and received PPCI at one referral hospital in Jordan. Data was collected from patients and their medical records during hospital stay using a structured data collection form. The MACE was assessed 30-days after PPCI through phone calls with patients and confirmed from medical records.

Results:
The study included 150 patients with ACS, 82.7% (n= 124) of them were males. The mean age of patients was 57.68 (SD= 11.19) years. Types of ACS include stable angina 5.3% (n=8), unstable angina 24% (n=36), NSTEMI 28.7% (n=43), and STEMI 24% (n=36). All patients had interventional PCI with balloon and stent insertion. The mean of SIRI was 24.45 (SD=25.49) and the mean of SII was 663.30 (SD= 403.75). Rate of MACE as composite outcome 30-days after PPCI as 24.7% (n=37). The most MACE was unplanned repeat revascularization (n=14, 38% of MACE). Significant association between SIRI and SII, and MACE was found

SIRI:(Χ
2
(2)> = 12.63, p = 0.001), SII:(Χ
2
(2)> = 4.23, p = 0.03)

.

Conclusion:
The SIRI and SII are inflammatory biomarkers that should be studied as potentially predictors of MACE among patients presented with ACS.
Abstract 4125157: Efficacy of Adding Sodium-Glucose Co-Transporter 2 Inhibitor versus Standard Therapy Alone in Post-Percutaneous Coronary Intervention Patients: A Systematic Review and Meta-Analysis
Authors: Rovari Gustavo , Rimolo Lorena , Chierici Pereira Lucas , Francisco Gomes Wilton
Published: November 2024

Background:
Recent evidence suggests that sodium-glucose cotransporter-2 inhibitors (SGLT2-i) may improve outcomes in patients with coronary artery disease (CAD) through various physiological pathways. However, their impact on patients who have undergone percutaneous coronary intervention (PCI) is not well established. This meta-analysis aims to evaluate the effectiveness of additive SGLT2 inhibitors versus standard therapy alone in patients with CAD after PCI.

Methods:
A systematic search was conducted across the Medline, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) and observational studies that compared the addition of SGLT2 inhibitors to standard therapy versus standard therapy alone in patients post-PCI. The outcomes analyzed were Major Adverse Cardiovascular Events (MACE), all-cause death, cardiovascular death, recurrent acute myocardial infarction (AMI), nonfatal stroke, revascularization, and hospitalization for heart failure (HF).

Results:
A total of 7 studies met the inclusion criteria, encompassing a total of 11,800 individuals (5,004 on SGLT2-i and 6,796 non-SGLT2-i; mean age of 62.7 years; 28% women; 95% diabetic patients). SGLT2 inhibitors significantly reduced the risk of all-cause mortality (RR 0.6, 95% CI: 0.5-0.72, p<0.01), cardiovascular death (RR 0.39, 95% CI: 0.16-0.94, p=0.03) and hospitalization for HF (RR 0.55, 95% CI: 0.4-0.76, p<0.01) compared to standard therapy alone. The occurrence of the composite endpoint (MACE) (RR 0.67, 95% CI: 0.44-1.01, p=0.056), any revascularization (RR 0.93, 95% CI: 0.57-1.53, p=0.784), recurrent AMI (RR 0.70, 95% CI: 0.41-1.18, p=0.176) and stroke (RR 0.94, 95% CI: 0.68-1.30, p=0.717) did not differ significantly between groups.

Conclusions:
Adding SGLT2 inhibitors to standard therapy significantly improved cardiovascular outcomes in patients with CAD who have undergone PCI, including reduced mortality and hospitalization for HF rates, with similar rates of recurrent AMI, coronary revascularization and stroke. These findings support the consideration of adding SGLT2 inhibitors as part of the therapeutic regimen for post-angioplasty patients, especially those with diabetes.
Abstract 4125263: Influence of sexual orientation-related nondiscrimination laws on 30-year CVD risk among sexual minority and heterosexual adults
Authors: Sharma Yashika , Philbin Morgan , Everett Bethany , Dwyer Caleigh , Bhargava Anisha , Doan Danny , Beach Lauren , Caceres Billy
Published: November 2024

Introduction:
Discriminatory policies are associated with worse mental health and substance use outcomes among sexual minority adults. Despite a higher risk of cardiovascular disease (CVD) than heterosexual adults, there is limited evidence on structural determinants of cardiovascular health among sexual minority adults. Therefore, we examined whether changes in sexual orientation-related nondiscrimination laws were associated with 30-year CVD risk among sexual minority and heterosexual adults.

Hypothesis:
We hypothesized that changes in sexual orientation-related nondiscrimination laws would be more strongly associated with 30-year CVD risk among sexual minority adults relative to exclusively heterosexual adults.

Methods:
We used longitudinal data from Waves III (2001-2002), IV (2008-2009), and V (2016-2018) of the National Longitudinal Study of Adolescent to Adult Health. We assessed changes in four state-level sexual orientation-related nondiscrimination laws (i.e., employment discrimination, same-sex marriage, hate crime statutes, and same-sex adoption) between Waves III and IV. Changes in sexual orientation-related nondiscrimination laws were categorized as unchanged (reference), improved, or worsened. We assessed 30-year CVD risk using the Framingham Risk Score at Wave V. We ran sex-stratified linear regression models adjusted for demographic factors to examine whether the association between change in nondiscrimination laws with 30-year CVD risk was moderated by sexual orientation (i.e., exclusively heterosexual, mostly heterosexual, homosexual/bisexual).

Results:
The sample included 3,827 participants with a mean age of 28.7 (±1.75) years, of whom 83.1% identified as exclusively heterosexual, 51% as female, and 15% as Black. Compared to heterosexual participants of the same sex, an improvement in nondiscrimination laws was associated with lower 30-year CVD risk among mostly heterosexual women (B -4.57, 95% CI = -8.06, -1.08) and homosexual/bisexual men (B -10.91, 95% CI = -19.33, -2.49). In contrast, compared to exclusively heterosexual women, a worsening of nondiscrimination laws was associated with higher 30-year CVD risk among homosexual/bisexual women (B 5.26, 95% CI = 0.30, 10.21). No differences were found between mostly heterosexual and exclusively heterosexual men.

Conclusions:
Findings suggest that efforts to enhance policies prohibiting sexual orientation-related discrimination may significantly reduce CVD risk among sexual minority adults.
Abstract 4125419: Very-Low-Density Lipoprotein Induces Neuronal Growth with Increased Tyrosine Hydroxylase Expression through Cardiomyocyte-Secreted Exosomes in Metabolic Syndrome
Authors: Lan Alexander , Lee Hsiang-Chun
Published: November 2024

Introduction:
Metabolic syndrome (MS) is an important predisposing factor for atrial fibrillation, and is highly related to the autonomic nervous system. Triglyceride-rich very-low-density lipoprotein (VLDL) has specific VLDL receptors (VLDLR), which are abundantly expressed in cardiomyocytes.

Hypothesis:
VLDL affects neuronal growth through cardiomyocyte-secreted exosomes in metabolic syndrome.

Goals/Aims:
To determine whether exosomes from VLDL-incubated cardiomyocytes can alter neuronal proliferation.

Methods/ Approach:
HL-1 cardiomyocytes were incubated with VLDL isolated from human subjects with MS, and exosomes were extracted at the end of the incubation period. VLDLR knockdown HL-1 cells were used to determine the role of VLDLR in exosome secretion. The molecular contents of exosomes were determined by mass spectrometry, which identified neurotropic proteins only detected in the exosomes of MS VLDL-incubated cardiomyocytes. We selected transmembrane protein 14B (TMEM14B) to investigate its effect on neuronal proliferation in P19 cells.

Results:
Regardless of the knockdown or overexpression of VLDLR in HL-1 cardiomyocytes, exosomes isolated from after VLDL incubation were shown to cause 2.062-fold and 2.084-fold expression of tyrosine hydroxylase (TH) in P19 cells, relative to P19 cells induced by non-VLDL-treated HL-1 cardiomyocyte-secreted exosomes. A similar trend could be seen with HL-1 cardiomyocytes without VLDLR editing, as VLDL-incubated HL-1 cardiomyocytes produced exosomes that could cause 1.926-fold increase in P19 TH expression, relative to treatment by exosomes from HL-1 cardiomyocytes without VLDL-incubation. The P19 cells incubated with TMEM14B demonstrated increased neurite length, with an average of 2.342-fold neurite length when compared with that of control cells.

Conclusions:
VLDL in MS induced HL-1 cardiomyocytes to secrete exosomes containing neurotrophic molecules and increased dendritic growth of neuronal cells. This effect was VLDLR-independent and was partially caused by TMEM14B in the exosomes.
Abstract 4125511: L-shaped association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and arterial stiffness: a cross-sectional study
Authors: Wei Taotao , LIN XIN , Yu Jing
Published: November 2024

Background:
Serum lipids and ratios are known to be associated with cardiovascular disease (CVD). However, studies on NHHR and the association with arterial stiffness in the US population have not been reported. We sought to investigate the relationship between NHHR and arterial stiffness by arterial stiffness in subjects from the US population assessed by ePWV.

Methods:
This study included 23, 456 adults from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2016. Multivariate linear regression analysis, threshold effects, smooth curve fitting, and subgroup analysis. We aimed to elucidate the relationship between NHHR and risk of arterial stiffness.

Results:
The mean age of the population in this study was 49.56 ± 17.58 yrs. The mean NHHR was 2.97 ± 1.48, and in the fully adjusted model, a negative correlation was observed between NHHR and ePWV scores (β = -0.01, 95% CI: -0.02, -0.00), with the highest tertile of the NHHR having a mean ePWV score that was 0.06 units lower than the lowest quartile of the NHHR by 0.06 units (β = -0.06, 95% CI: -0.09, -0.02; P for trend = 0.0068). An L-shaped relationship between NHHR and ePWV scores was found by using smoothed curve fitting. The cutoff value was 2.13, and in the hypertensive population, the cutoff value was 1.93.

Conclusions:
There is an L-shaped association between NHHR levels and atherosclerosis in adults in the United States, and controlling NHHR is clinically important for reducing the risk of developing atherosclerosis.
Abstract 4125636: Impaired blood pressure regulation in post-COVID-19 postural orthostatic tachycardia syndrome: novel disease mechanisms beyond sinus tachycardia
Authors: Johansson Madeleine , Stahlberg Marcus , Ricci Fabrizio , Lewinter Christian , Hamrefors Viktor , Nilsson Peter , Sutton Richard , Fedorowski Artur
Published: November 2024

Background:
Postural orthostatic tachycardia syndrome (POTS) is a prevalent cardiovascular disorder after COVID-19 infection. Although POTS is characterized by the presence of sinus tachycardia, other hemodynamic disturbances including blood pressure (BP) regulation, remain largely unexplored.

Aims:
We investigated BP changes using 24-hour ambulatory-BP-monitoring in patients with new-onset POTS after COVID-19 compared with pre-pandemic healthy controls.

Methods:
We performed a case-control study in 100 verified COVID-19 patients with new-onset POTS (mean age 40.0±12.9 years, 85% women) diagnosed by positive head-up tilt-testing versus 100 healthy controls (mean age 45.0±14.6 years, 70% women) from a population-based cohort with negative active standing test, no history of syncope, orthostatic intolerance, or endocrine disease. We analyzed 24-hour Systolic BP (SBP) and hypotensive SBP episodes (<80, <90, and <100mmHg).

Results:
Study characteristics are illustrated in the
Table
. Post-COVID-19 POTS patients had significantly higher nighttime-SBP, but not daytime-SBP, and more daytime SBP hypotensive episodes (<80, <90, and <100 mmHg,
Figure
) compared with controls. Non-dipper (34% vs 19%, p<0.001) and reverse dipper patterns (9% vs 0 %, <0.001) were more frequent in post-COVID-19 POTS. In the logistic regression, post-COVID-19 POTS was associated with significantly higher mean 24h SBP (odds ratio (OR) 1.08, 95%CI 1.04-1.11, p<0.001) and nighttime SBP (OR 1.07, 95%CI 1.04-1.10, p<0.001), independently of age and sex.

Conclusions:
Post-COVID-19 POTS patients demonstrate higher mean 24h and nighttime systolic BP, and show signs of disrupted BP regulation compared with healthy controls. They also have more daytime hypotensive episodes. Future studies are needed to assess if post-COVID-19 POTS patients may benefit from tailored BP therapy.
Abstract 4125701: Race and Ethnicity Are Associated with Diagnosis and Management of Wolff-Parkinson-White Pattern in Children
Authors: Hakimi Mathew , Asztalos Ivor , Zavez Alexis , Mondal Antara , Iyer Ramesh , Shah Maully , Srinivasan Chandra , Vetter Victoria , Janson Christopher
Published: November 2024

Background:
Racial and ethnic disparities have been reported in catheter ablation in adults. There are limited data on the impact of race/ethnicity on the diagnosis and management of children with Wolff-Parkinson-White pattern (WPW).

Hypothesis:
Diagnosis of WPW by electrocardiogram (ECG) and risk stratification by exercise stress test (EST) and electrophysiology study (EPS) will differ by race/ethnicity in children.

Methods:
We performed a retrospective cohort study of patients 0-21 years old, excluding those with congenital heart disease, at a children’s hospital from 1991-2021. The primary exposure was race/ethnicity. Outcomes were 1) diagnosis of WPW on ECG, 2) undergoing EST, and 3) undergoing EPS. Likelihood and time to outcome were assessed with multivariable logistic regression adjusted for birth year and Cox regression, respectively.

Results:
The cohort consisted of 1,638,746 patients (White 53.0%, Black 21.0%, Hispanic 6.8%, Asian 4.2%, Multi-racial 2.0%, Other 11.0%, and Missing 1.7%). WPW was diagnosed in 898 patients (0.05%). After adjusting for birth year, Asian, Black, and Other race were associated with lower odds of WPW diagnosis compared to White patients (OR 0.57, 0.66, 0.70; p≤0.01). There was no association between race and age at first diagnosis (p=0.2). A total of 616 WPW patients (69%) underwent EST. Compared with White patients, Asian, Hispanic, and Other race were less likely to undergo EST (OR 0.39, 0.59, 0.62; p≤0.04), and those who did had their EST at later ages (HR 0.59, 0.65, 0.46; p≤0.04). A total of 739 WPW patients (82%) underwent EPS. Compared with White patients, Black, Hispanic, and Other race were less likely to undergo EPS (OR 0.44, 0.53, 0.59; p≤0.02), and those who did had their EPS at later ages (HR 0.60, 0.63, 0.66; p≤0.004).

Conclusion:
This analysis found that non-White racial and ethnic groups are less likely to be diagnosed with WPW. This may reflect differences in WPW prevalence by race/ethnicity, but differential access to ECG cannot be ruled out. Among WPW patients, however, Asian and Hispanic patients are approximately half as likely to undergo EST, while Black and Hispanic patients are approximately half as likely to undergo EPS, compared to White patients.
Abstract 4125729: Elevated Pre-Procedural Serum Natriuretic Peptide Levels Are Associated with All-Cause Mortality in Patients Undergoing Transcatheter Edge-to-Edge Mitral Valve Repair: A Systematic Review and Meta-Analysis
Authors: Cui Edward , Hung Annie , Ko Grace , Cheung Holly , Day Andrew , Norman Patrick , Abuzeid Wael
Published: November 2024

Background:
Transcatheter edge-to-edge mitral valve repair (TEER) is an established procedure in patients with severe mitral regurgitation (MR) and elevated surgical risk on optimal medical therapy. However, there remains considerable mortality in this patient population. Some studies have shown that serum brain natriuretic peptide (BNP) and N-terminal pro b-type natriuretic peptide (NT-proBNP) predict all-cause mortality after TEER, whereas other studies have shown mortality to be independent of these markers. To address this gap in knowledge, we sought to examine the existing literature to determine whether there is an association between pre-procedural serum natriuretic peptides and mortality after TEER.

Hypothesis:
Among patients undergoing TEER, elevated pre-procedural BNP and NT-proBNP are associated with increased all-cause mortality.

Methods:
Databases including MEDLINE, Embase, and Cochrane Library were searched from inception through September 2023 for studies assessing pre-procedural serum natriuretic peptide levels and mortality among patients undergoing TEER. Pooled hazard ratios (HR) and standardized mean differences (SMD) were calculated using a random-effects model estimated by restricted maximum likelihood with the Hartung-Knapp modification.

Results:
A total of 30 studies comprising 10259 patients undergoing TEER met inclusion criteria. 25 studies measured NT-proBNP and 5 studies measured BNP. Elevated pre-procedural NT-proBNP (>5000 or >10000 pg/mL) was associated with increased all-cause mortality in both adjusted (HR = 2.94; 95% CI = 1.75 - 4.95; I2 = 46.8%) and unadjusted (HR = 5.16; 95% CI = 1.85 - 14.40; I2 = 0.0%) analyses (Figures 1 and 2). Pre-procedural BNP and NT-proBNP were also significantly lower among survivors at 12 months compared to non-survivors (SMD = 0.82; 95% CI = 0.37 - 1.27; I2 = 78.3%) (Figure 3). This association was demonstrated in patients with primary or secondary MR.

Conclusions:
Pre-procedural BNP and NT-proBNP levels are significant predictors of all-cause mortality in patients undergoing TEER for primary or secondary MR. This supports the inclusion of BNP or NT-proBNP in pre-procedural assessments to help inform patient discussions and guide post-procedural follow-up and monitoring.
Abstract 4125893: Deciphering the Mechanism of Action of Drug Combinations by Boolean Modeling of Transcriptomes: a Case Study of Atorvastatin/Simvastatin and Ezetimibe
Authors: Wang Ruisheng , Pedrelli Matteo , Ahmed Osman , Garagnani Paolo , Parini Paolo , Loscalzo Joseph
Published: November 2024

Introduction:
Drug combinations offer increased therapeutic efficacy and reduced toxicity and plays a vital role in treating chronic complex diseases. Understanding a drug combination's mechanism of action (MoA) can provide important insights into its therapeutic efficacy. The MoA of many FDA-approved drugs, however, often remains unclear.

Methods:
In this study, we investigated the combination of a statin [atorvastatin (ATO) or simvastatin (SIM) plus ezetimibe (EZE)] and utilized drug-treated RNA-seq transcriptome data from SOAT2-only-HepG2 cells (treated with ATO 5 umol/L, EZE, 25 umol/L, their combination or vehicle) and from liver biopsies of patients with uncomplicated cholesterol gallstone disease in the Stockholm Study (a single-blind, randomized trial with SIM 80 mg daily, EZE 10 mg daily, their combination, or placebo) to decipher the underlying molecular mechanisms of the drug combination. We proposed a Boolean logical modeling framework to simulate the MoA of a drug combination. Specifically, fourteen two-variable Boolean models were used to describe the combinatory relationships of ATO/SIM and EZE. Thereafter, a pattern matching approach was applied to associate drug-induced differentially expressed genes with the idealized differential expression templates derived from Boolean models.

Results:
We found 1,560 and 594 genes differentially expressed in at least one treatment condition in SOAT2-only-HepG2 cells and liver biopsies, respectively. Our analysis revealed both expected and novel combinatorial modes of ATO/SIM and EZE. For example, ATO independently activates downstream genes (i.e. B
4
(ATO,EZE)=ATO), and ATO and EZE synergistically inhibits downstream genes (i.e. B
15
(ATO,EZE)=NOT (ATO AND EZE)) , as the two most prevalent MoAs in SOAT2-only-HepG2 cells (Figure 1). Similarly, the combination of SIM and EZE synergistically inhibiting downstream genes was also the most prevalent MoA in the liver biopsies. We mapped the downstream genes of each combinatorial mode to the human interactome and obtained underlying subnetworks, which are important for understanding the therapeutic effects of the drug combination. Functional enrichment and disease-association analyses of the downstream suggest the additional therapeutic indications of the drugs.

Conclusion:
Drug-induced transcriptomes are informative in deciphering the MoA of drug combinations using Boolean logical modeling. This framework can be easily extended to the combinations of three drugs.