bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4139703: Developing normal values for pulse wave velocity in healthy young people
Authors: Kodithuwakku Vimarsha , Breslin Monique , Hersant Jeanne , Bruno Rosa , Boutouyrie Pierre , Urbina Elaine , Gall Seana , Climie Rachel
Published: November 2024

Background:
A high prevalence of cardiovascular disease (CVD) globally prompts the necessity of a surrogate marker to identify CVD development at the subclinical stage. Observation of early alterations to the vasculature has proven to be beneficial in identifying adults who have an increased risk of CVD. Hence, utilizing vascular ageing as an effective, non-invasive, subclinical marker in assessing cardiovascular risk in young people could be promising for the reduction of CVD incidence. Pulse wave velocity (PWV) is a marker of vascular ageing, and even though the importance of PWV in cardiovascular health assessment in adults has been established, to use it routinely to evaluate young people at risk, normal values need to be determined. The Youth Vascular Consortium (YVC) is an international collaborative that was established to comprehensively investigate vascular ageing with a range of measures among young people. This study aimed to develop normal values for PWV measured by commonly used devices among healthy young people using data from the YVC.

Methods:
This retrospective study included data on demographics, anthropometric, biochemical and vascular ageing measures collected from participants aged 1 to 40 years. Generalised additive models were used to derive percentile curves for the PWV data by age. Observed and predicted percentiles at years of age were reported by sex, geographical region and device.

Results:
The YVC collected data on 36,973 participants from 24 countries across five different regions. Of these, 19,018 participants (mean age = 17 years, 51% female, 71% European) were classified as healthy based on their systolic and diastolic blood pressure, serum glucose, serum cholesterol and body mass index. Six devices were used to measure PWV (30% SphygmoCor). Device-specific percentile curves for PWV against age were constructed and an increasing trend in PWV was identified with age for both males and females.

Conclusion:
This study provided normal values for PWV measured with six different devices for young people as age and sex-specific percentile curves. These curves may be applied clinically to identify young people with impaired vascular ageing and thus, those who may be at risk of overt CVD.
Abstract 4139722: Association between Age at Menarche and Age at Onset of Angina Pectoris: An Analysis of NHANES Data from 2017-2020
Authors: Nuchpramool Prachawanee , Kulthamrongsri Narathorn , Wanichwecharungruang Nisha , Suriyathumrongkul Napat , Yinadsawaphan Thanaboon , Wattanachayakul Phuuwadith , KOOKANOK Chutawat , Saowapa Sakditad , Kanthajan Tatchaya , Prasitsumrit Vitchapong , Kulthamrongsri Kritpong , Thiravetyan Ben , Suenghataiphorn Thanathip , Wannaphut Chalothorn , Srikulmontri Thitiphan , Tantisattamo Ekamol
Published: November 2024

Background:
There is suspicion that estrogen may protect against atherosclerosis. Women who experience menarche earlier, and thus have earlier estrogen exposure, might develop atherosclerosis later. The relationship between menarche age and the onset of angina pectoris, a symptom of coronary artery disease, remains unknown.

Goal:
This study aims to find the correlation between menarche age and the onset age of angina pectoris, and the association between early menarche (onset of menarche ≤ 10 y/o) and early onset of angina pectoris (onset of angina pectoris ≤ 40 y/o).

Methods:
A cross-sectional study using a population from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). The question collects self-reported data on onset of menarche and onset of angina pectoris. The relationship between menarche age and age in onset of angina pectoris was analyzed by linear and logistic regression analysis. Multivariate analysis adjusted for race, age, body mass index (BMI), smoking , diabetes mellitus (DM), hypertension, and dyslipidemia status.

Results:
Among 4,816 females who reported their menarche age, 88(1.8 %) have had an angina pectoris. The study involved 82 females who reported both the age of menarche and the age of onset of angina pectoris. The mean ± SD of the age at menarche and the age at onset of angina pectoris was 12.53 ± 1.79 y/o and 51.66 ± 15.16 y/o, respectively. The study found a significant association between the menarche age and the age at onset of angina pectoris. After adjusting for confounders, we found that every 1-year increase in the age of menarche will delay the onset of angina pectoris by 1.43 years, with a 95% CI of 0.01 to 2.86.(Table 1A,Graph 1A-1B)

We also found that early menarche has a significantly increased risk 2.8 times (95%CI: 1.3, 6.2) of early onset of angina pectoris.After adjusting for confounders, the association became even stronger. The odds ratio (OR) increased to 3.3 (95%CI: 1.4, 8.0), indicating that women with early menarche were 3.3 times more likely to experience early angina pectoris compared to those with later menarche.(Table 2A)

Conclusion:
In contrast to our hypothesis, age at menarche is positively associated with onset of angina pectoris. The earlier onset of menarche is linked to the earlier onset of angina pectoris. We suspected that factors beyond estrogen levels may contribute to this unexpected finding. Additional studies are needed to examine the cause of this correlation.
Abstract 4139723: Safety and Efficacy of Antisense Oligonucleotides On Triglyceride and Apolipoprotein C-III Levels in Hypertriglyceridemia; A Network Meta-Analysis Of Randomized Controlled Trials
Authors: Abdelsayed Kerollos , Mahmoud Abdelrahman , Najah Qasi , Almahdy Mohamed Ahmed , Abdulkader Anas , Ali Karim , Tabassum Shehroze , Abouzid Mohamed , Banour Sandi , Abdelazeem Basel
Published: November 2024

Background:
Hypertriglyceridemia is an independent risk factor for cardiovascular diseases. Apolipoprotein C-III (APOC3) inhibition through the antisense oligonucleotides volanesorsen, olezarsen, and plozasiran, reduced triglycerides in the previous trials. However, the safety and efficacy of the three medications have not been compared yet.

Methods:
A network meta-analysis was performed to compare multiple doses of the three medications to each other through the placebo. Nine randomized controlled trials (RCTs) were retrieved by searching PubMed, EMBASE, Web of Science, SCOPUS, and Cochrane. The mean difference (MD) and 95% confidence interval (CI) were used for continuous outcomes. The risk ratio (RR) and 95% CI were used for dichotomous outcomes.

Results:
A total of 782 patients were included. Volanesorsen 300 mg once weekly showed the most significant reduction in triglyceride levels (MD = -90.98%, 95% CI: [-109.2%; -72.8%];
p<0.01
). Only plozasiran once monthly, regardless of the dose, showed a non-significant reduction in triglycerides, which should be taken with caution as the data were derived from a phase 1 trial with a small sample size. All the regimens significantly reduced APOC3 levels compared to placebo with plozasiran 100 mg and 50 mg once monthly and volanesorsen 300 mg once weekly, showing the most significant reduction (MD range: -92.8% to -88.4%;
p<0.01
). Plozasiran regimens, especially the 25 mg, 50 mg, and 10 mg once monthly dosages, respectively, reduced total cholesterol levels the most compared to placebo (MD range: -30.6% to -23.5%;
p<0.01
). Only volanesorsen, regardless of the dose, did not significantly reduce total cholesterol compared to placebo. None of the treatments showed a statistically significant difference in the adverse events rate compared to placebo.

Conclusion:
APOC3 antisense oligonucleotide inhibitors effectively reduced triglyceride, APOC3, and total cholesterol levels in hypertriglyceridemia, with an acceptable safety profile. However, due to the relatively small sample size, the results should be interpreted with caution. Further research is needed to confirm the beneficial effects of APOC3 inhibitors and provide strong evidence on the effects of each medication regimen.
Abstract 4139724: Heart Transplant in Geriatric Population from 2000 to 2023: UNOS Database Study
Authors: Yoo Thomas , Linares Velandia Juan David , Seliem Ahmed
Published: November 2024

Background:
Advancements in heart transplant has expanded boundaries to greater range of patients to receive transplant. Despite concerns of increased morbidity and mortality, data from previous studies showed selected patients 70 years or older who underwent heart transplant had similar morbidity and mortality compared to younger patients. With growing population age and increase in technology, transplant candidacy is expanded to selected robust geriatric patients.

Objective(s):
Determine change in the number of transplant cases and the percent from total yearly cardiac transplant in geriatric population

Method:
Heart transplant recipients of all ages from 2000 to 2023 were identified in the United Network for Organ Sharing (UNOS) database and stratified into different age groups. Primary outcomes of interest included number of heart transplant cases and percentage from total yearly transplant.

Results:
In total, we identified 66,079 heart transplant recipients from 2000 to 2023. Among these patients, 9,964 (12.40%) were patients aged 65 above and 28,554 (45.50%) were 50-64 years old (figure 1A). There was an overall increase in the number of heart transplants from 2000 to 2023, 2,199 to 4,545 cases per year, respectively. There was an increase in the number of heart transplants in the geriatric population from 216 to 841 (figure 1B). From 2000 to 2013, there was an increase in the percent of transplant recipients in patients 65 years and older from 9.80% to 17.60%, after which remained stable (figure 1C). There was a relative decrease in proportion of patients 50-64 years from 2000 to 2014, from 51.10% to 42.80%, respectively. The number of cardiac transplants among 50-64 year old group from 2000 to 2008 decreased from 1,123 to 920 then increased again by 2014.

Conclusion:
There has been a significant increase in the total number of heart transplants from 2000 to 2023. Currently, heart transplants in geriatric population consist of a significant portion of total heart transplants close to 1 of 5 transplants that occur per year (18% to 19%). This number has grown from 9.80% (2000) to 18.50% (2023) among all heart transplants per year.
Abstract 4139728: Aortic Arch Calcification Among Cigarette Smokers: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Ansari Salman , Trujillo Robert , McClelland Robyn , Budoff Matthew
Published: November 2024

Background and Aims:
Cigarette smoking is a known contributor to cardiovascular disease (CVD) and is associated with increased prevalence of coronary artery calcium. However, despite this clinical significance, calcium deposition in other vascular beds, specifically the aortic arch, has yet to be thoroughly investigated among cigarette smokers.

Methods:
The study population comprised 3026 participants who underwent non-contrast chest CT scans in MESA exam 5. Aortic arch calcium (AAC) is defined as calcification in the transverse aortic arch, as measured using the Agatston method on chest CT scans. Log-transformed AAC scores were used for all analyses. Multivariate linear regression models were fit to assess the relationship between log-AAC and cigarette smoking status (never-smoked, former smoker, current smoker). Cox proportional hazard models were fit to investigate the relationship between log-AAC and incident CVD and mortality for those with a history of smoking (former¤t smokers). All models were adjusted for demographic and traditional clinical risk factors.

Results:
After excluding those with missing variables, 2196 participants were included in the final analysis, of which 1119 self-identified as never smokers, 901 as former smokers, and 176 as current smokers. Estimated mean log-AAC was 0.557 (p<0.001) log-Agatston units higher in former smokers compared with never smokers [95% CI: 0.374 - 0.741], and 1.030 (p<0.001) log-Agatston units higher in current smokers compared with never smokers [95% CI: 0.703 - 1.358]. Among ever-smokers (current or former smokers), a one log-Agatston unit increase in log-AAC was associated with a 20.6% (p = 0.002) increased risk for CVD events [95% CI: 7.4% - 35.5%] and a 12% (p = 0.020) increased risk for mortality [95% CI: 2% - 23%].

Conclusion:
This study demonstrated a potential association between cigarette smoking and AAC scores, with significant differences in AAC among current, former, and never smokers. Furthermore, AAC is associated with incident cardiovascular events and mortality among those with a history of smoking.
Abstract 4139732: Timing of Anticoagulation in Pulmonary Embolism with Nontraumatic Intracranial Hemorrhage: A Multi-National Database Study
Authors: Chang Kyle , Hambach Bryce , Nareddy Suhas , Prucnal Christiana , Hernandez Elvin , Sovory Lisa
Published: November 2024

Background:
Pulmonary embolism (PE) occurs in 1% of patients with nontraumatic intracranial hemorrhage (ICH) despite thromboprophylaxis. Anticoagulation is the primary treatment of hemodynamically stable PE; however, risks of bleeding complications in ICH exist. We investigated the optimal timing of anticoagulation in patients with PE and ICH using a large retrospective database.

Methods:
We included patients with nontraumatic ICH and PE without acute cor pulmonale or prior long-term anticoagulation from the TriNetX Research Network. Patients were then categorized as early (0-3 days after ICH), intermediate (4-14 days), late (15-60 days), or no anticoagulation. Chi-square and independent
t
-tests were used for bivariable analyses. Cohorts were 1:1 propensity score-matched by 17 covariables including demographic information and comorbidities. Outcomes were all-cause mortality, neurological deficits due to ICH, and extracranial hemorrhage 90 days after ICH.

Results:
Of 13,042 included patients, mean age was 65±16 and 45% were female. Those receiving early anticoagulation after ICH had higher risk of mortality (RR=1.29, 95% CI: 1.20-1.38), neurological deficits, and extracranial hemorrhage compared to no anticoagulation. Intermediate anticoagulation had similar outcomes to no anticoagulation. Late anticoagulation had lower risk of mortality (RR=0.78, 95% CI: 0.66-0.92) and no significant difference in other outcomes.

Conclusions:
In patients with ICH and PE without acute cor pulmonale, early anticoagulation was associated with increased mortality, neurological deficits, and extracranial hemorrhage compared to no anticoagulation. Late anticoagulation was associated with decreased mortality and similar risks of neurological deficits and extracranial hemorrhage.
Abstract 4139747: Inhibition of Acetyl -CoA Carboxylase 2 (ACC2) enhances fatty acid oxidation and improves cardiac function and survival in a severe model of heart failure
Authors: Usui Mai , Tsurekawa Yu , Ikehara Tatsuya , Shimazaki Atsuyuki , Vijayakumar Archana , Myers Robert , Subramanian G. Mani , Murakami Eisuke
Published: November 2024

Heart failure (HF) is characterized by disordered energy metabolism including impaired mitochondrial oxidation and altered energy substrate preference. In triglyceride (TG) deposit cardiomyovasculopathy (TGCV; ORPHA code 565612), a rare form of HF characterized by impaired fatty acid oxidation (FAO), massive TG accumulation occurs in cardiac muscle and vasculature due to deficiency of adipose triglyceride lipase (ATGL). Since acetyl-CoA carboxylase 2 (ACC2) regulates fatty acid transport into mitochondria for oxidation, we hypothesized that genetic deletion or pharmacologic inhibition of ACC2 may improve cardiac function in the
Atgl
knockout (KO) mouse model of TGCV. Relative to
Atgl
KO mice,
Atgl/Acc2
double KO mice had reduced cardiac TG accumulation and fibrosis, and significant improvements in cardiac function by echocardiography, locomotor activity, and survival (log-rank p <0.0001). These findings were recapitulated by treatment of
Atgl
KO mice with TLC-3595, a highly selective, systemic, small molecule ACC2 inhibitor in development for type 2 diabetes (
Figure
). After a single dose of TLC-3595 to
Atgl
KO mice, dose-dependent reductions in cardiac malonyl-CoA levels and TG content were observed. Further, in a detailed time-course echocardiographic analysis,
Atgl
KO mice had reduced left ventricular ejection fraction and evidence of cardiac remodeling which was ameliorated by TLC-3595 treatment. Metabolomic profiling of cardiac tissue revealed ACC2-specific changes, including reduced malonyl-CoA and increased acylcarnitines, consistent with increased FAO with TLC-3595 treatment. Moreover, levels of TCA cycle metabolites and acetylcarnitine were reduced in
Atgl
KO mice but increased with ACC2 deletion or TLC-3595. In summary, ACC2 deletion or pharmacologic inhibition restored cardiac energy metabolism towards increased FAO in
Atgl
KO mice, resulting in improved cardiac function and survival. These findings support the therapeutic targeting of ACC2, including with the selective small molecule ACC2 inhibitor TLC-3595, for the treatment of patients with HF associated with FAO deficiency.
Abstract 4139817: Systolic Blood Pressure in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Pooled Participant-Level Analysis of 4 Large-Scale Trials
Authors: Lu Henri , Kondo Toru , Claggett Brian , Vaduganathan Muthiah , Neuen Brendon , Beldhuis Iris , Jhund Pardeep , Mc Causland Finnian , Anand Inder , Pfeffer Marc , Pitt Bertram , Zannad Faiez , Zile Michael , McMurray John , Solomon Scott , Desai Akshay
Published: November 2024

Background:
Hypertension is common in patients with heart failure with preserved ejection fraction (HFpEF). Treatment of systolic blood pressure (SBP) to a target <130 mmHg in this population is often recommended based on general ACC/AHA and ESC hypertension guidelines but limited data are available to substantiate this recommendation in patients with HF. We aimed to explore the impact of baseline SBP on cardiovascular (CV) outcomes in a pooled dataset of 4 large, well-characterized cohorts of patients with HF with mildly reduced EF (mrEF) or HFpEF.

Methods:
I-PRESERVE, TOPCAT, PARAGON-HF and DELIVER were global, multicenter, randomized clinical trials testing irbesartan, spironolactone, sacubitril/valsartan and dapagliflozin respectively, against either a placebo or an active control (valsartan, in PARAGON-HF), in patients with HF and a LVEF >40% (in DELIVER) or ≥45% (in all other 3 trials). The continuous relationship between baseline SBP and the incidence rates (IR) of 1
st
HF hospitalization (HFH) or CV death was analyzed with restricted cubic splines and adjusted for known risk factors of CV disease.

Results:
A total of 18,627 patients (mean age 71±9 years, 49% men, mean SBP 131±15 mmHg) were included. Over a median follow-up of 2.9 years, 3,852 patients experienced a first HFH or CV death (7.4 events per 100py). The relationship between the IR of 1
st
HFH or CV death and SBP appeared to be nonlinear, J-shaped (
Figure 1
), with a nadir of IR observed for SBP values between 120 and 130 mmHg, and an increase for SBP values above 130 mmHg. Above 130 mmHg, each 5 mmHg-increase in SBP was associated with a significantly higher risk of the primary outcome (adjusted HR: 1.07; 95% CI: 1.05-1.10). When stratifying the study population by sex, men had a higher risk for 1
st
HFH or CV death across the spectrum of SBP. The J-shaped relationship remained consistent in both men and women (P
interaction
=0.43;
Figure 2
).

Conclusions:
Our analysis of a large pooled dataset from 4 clinical trials including over 18,600 patients with HFmrEF or pEF suggests a graded relationship between SBP and CV risk, with risk nadir at SBP between 120 to 130 mmHg, without evidence of difference according to sex.
Abstract 4139840: Impact of Sodium-Glucose Cotransporter 2 Inhibitors on Acute Kidney Injury Post Coronary Artery Bypass Grafting ：A Retrospective Cohort Study and Meta-Analysis
Authors: Zhou Xiaozheng , Yang Xiubin , Hua Kun
Published: November 2024

Background:
sodium-glucose cotransporter 2 inhibitors (SGLT2i) , a new type of oral hypoglycemics agent used to treat type 2 diabetes, have a positive effect on the progression of heart failure, but there is a concern with the association between SGLT2i and acute kidney injury (AKI).

Materials and Methods:
We retrospectively evaluated consecutive patients undergoing CABG surgery from January 2018 to December 2021 in the hospital. A cohort of patients who had been prescribed SGLT2i was identified and matched by propensity score with a cohort of patients who had not been prescribed SGLT2i in a ratio of 1:3. The primary outcome was AKI following CABG. Furthermore, a meta-analysis was conducted on the relationship between SGLT2i and acute kidney injury (AKI). Four studies, comprising a total of 25,116 patients, were included in the analysis.

Results:
A total of 403 patients who had received SGLT2i and 1209 without SGLT2i were included in the analysis. AKI was observed in 54 patients (13.4%) in the SGLT2i group and 373 patients (30.9%) in the non-SGLT2i group following CABG. The SGLT2i exhibited a lower incidence of AKI compared with the non-SGLT2i (P < 0.001). The findings of the meta-analysis indicated that SGLT2i was associated with a decreased incidence of AKI (P < 0.001; OR= 0.525, [95% CI, (0.437-0.631]).

Conclusion:
The results of our prospective study indicated a reduced risk of AKI in patients undergoing CABG and were treated with SGLT2i.
Abstract 4139844: Clinical Relevance of FFR-guided PCI According to Left Ventricular Systolic Function in Patients with Acute Myocardial Infarction and Multivessel Disease
Authors: Lee Yong-Kyu , Lee Seung Hun , Kim Hangyul , Ahn Joon Ho , Cho Kyung-Hoon , Kim Min Chul , Sim Doo Sun , Lee Joo Myung , Hong David , Hahn Joo-Yong , Kim Hyun Kuk , Park Keun Ho , Choo Eun Ho , Kim Chan Joon , Ahn Gyun , Doh Joon-Hyung , Lee Sang Yeub , Park Sang Don , Lee Hyun-Jong , Kang Min Gyu , Nam Chang-Wook , Choi Ki Hong , Park Taek Kyu , Yang Jeong Hoon , Song Young Bin , Choi Seung-Hyuk , Kim Ju Han , Ahn Youngkeun , Jeong Myung Ho , Gwon Hyeon-Cheol , Koh Jin-sin , Hong Young Joon
Published: November 2024

Background:
Fractional flow reserve (FFR) or angiography-guided complete revascularization was not evaluated in patients with acute myocardial infarction (MI) with reduced left ventricular ejection fraction (LVEF).

Objectives:
To evaluate impact of FFR-guided percutaneous coronary intervention (PCI) for AMI patients with multivessel disease according to left ventricular systolic function.

Methods:
We performed pre-specified analysis of FRAME-AMI trial which randomly allocated 562 patients into either FFR-guided PCI (FFR≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct related artery (IRA). Patients were classified by LVEF into the preserved (LVEF ≥50%) and reduced (LVEF <50%) groups. The primary end point was patient-oriented composite outcome (POCO), a composite of death, MI, and repeat revascularization.

Results:
Overall, 187 patients (33.3%) had reduced LVEF. At 4-year follow-up, AMI patients with reduced LVEF showed increased risk of MACE than those with preserved LVEF (18.9% vs. 10.8%; adjusted HR=2.65, 95% CI 1.53-4.58, P<0.001). FFR-guided PCI for non-IRA significantly reduced POCO among preserved LVEF group (3.3% vs. 19.0%; adjusted HR=0.23, 95% CI 0.09-0.59, P=0.002). Conversely, there was no significant difference in POCO between FFR and angiography-guided PCI among reduced LVEF group (17.0% vs. 21.0%; HR=0.64, 95% CI 0.31-1.32, P=0.227). The prognostic impact of FFR-guided PCI tended to increase as LVEF increased (adjusted HR for POCO: 0.69 vs. 0.66 vs. 0.25 vs. 0.20, respectively, for the LVEF ≤40% vs. 40-50% vs. 50-60% vs. ≥60%, interaction P=0.028).

Conclusion:
In acute MI patients with multivessel disease, FFR-guided PCI for non-IRA showed differential clinical impact according to left ventricular systolic function. The beneficial effect of FFR-guided PCI might be maximized among patients with preserved LVEF rather than reduced LVEF.
Abstract 4139850: Demographics and Regional Trends of Chronic Renal Failure- and Heart Failure-related mortality in older adults: Insights from CDC-Wonder Database 1999-2020
Authors: Ali Eman , Alim Ur Rahman Hafsah , Fahim Muhammad Ahmed Ali , Cheema Huzaifa Ahmad , Ahmad Adeel , Rehman Wajeeh , Dani Sourbha
Published: November 2024

Introduction:
The incidence of Heart Failure (HF) has increased as the US population ages, with Chronic Renal Failure (CRF) being a common comorbidity and risk factor for mortality. This study aims to identify annual, gender, race, and geographical trends in CRF-related mortality in patients with HF for older adults.

Methods:
We used ICD-10 (International Classification of Diseases 10th Revision) codes to retrospectively analyze death certificate data from the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database between 1999-2020 for patients ≥65 years old with concomitant HF and CRF. Age-adjusted mortality rates (AAMRs) per 100,000 people and Annual Percentage Change (APCs) and their respective 95% Confidence Intervals (CI) were also calculated for patient data grouped according to year, gender, race, and geography.

Results:
From 1999-2020, 425,854 deaths occurred from CRF and HF in patients ≥ 65 years. The overall AAMR was 46.1 (95% CI: 46 to 46.3), with the APC from 1999-2020 being 2.96 (95% CI: 1.84 to 4.32). Males reported higher AAMRs than females (overall AAMRs: 62.1 vs 36.2). Stratifying data by race revealed NH (Non-Hispanic) Black or African American to have the highest AAMR (62.2) followed by NH American Indian or Alaska Native (52.5), NH White (45.5) and Hispanic or Latino (37.2), with the NH Asian or Pacific Islander race having the lowest AAMR (30). According to the census region, the highest AAMRs were reported in the Midwest (54.3), followed by the West (45.1) and South (43.4), with the lowest AAMRs in the Northeast (42.3). Furthermore, Non-Metropolitan areas revealed higher AAMRs when compared to Metropolitan areas (54.4 vs 43.3). The states in the top 90
th
percentile were Indiana, Kentucky, Minnesota, North Dakota, and West Virginia. They had AAMRs nearly double those in the bottom 10th percentile, such as Arizona, Hawaii, Nevada, and New Mexico.

Conclusion:
Trends in CRF- and HF-related mortality in older adults have varied from 1999-2020, with the highest AAMRs being reported in men, NH Black or African Americans, Non-Metropolitan areas, and in the Midwest. Strategies to target precipitating events are necessary alongside further investigations to explain the trend variations.
Abstract 4139852: Plozasiran and Triglyceride Levels in Hypertriglyceridemia: Long-Term Efficacy and Safety Data From Subjects in an Open-Label Extension Trial
Authors: Ballantyne Christie , Watts Gerald , Rosenson Robert , Vasas Szilárd , Pall Denes , Clifton Peter , Nicholls Stephen , Azizad Masoud , Fu Ran , Muhsin Maan , Melquist Stacey , Hellawell Jennifer , Gaudet Daniel
Published: November 2024

Despite current modestly effective triglyceride (TG) lowering therapies, the availability of more effective agents for persistently lowering elevated TGs and risk of acute pancreatitis remains a continuing need. More recently identified triglyceride-rich lipoproteins (TRLs), specifically remnant cholesterol (RC)-rich particles, are important drivers of ASCVD risk independent of LDL-C, driving development of more effective TG-directed therapies. Apolipoprotein C3 (APOC3) raises TGs by inhibiting lipoprotein lipase (LPL) dependent and -independent pathways. Plozasiran, a RNAi agent targeting APOC3 mRNA in hepatocytes, demonstrated large reductions in circulating APOC3, TGs, TRL-RC with a good safety profile in placebo-controlled trials.

Here we report extension data to characterize long term safety and efficacy of plozasiran in subjects with elevated TGs.

Plozasiran was studied in subjects with mixed hyperlipidemia (entry TGs 150-499 mg/dl) and severe hypertriglyceridemia (entry TGs
>
500-4000 mg/dl) in separate Phase 2 trials (MUIR and SHASTA-2). Subjects completing double-blind, placebo-controlled treatment could enter this open-label extension. Endpoints included changes in fasting TG levels, other lipid and lipoprotein parameters and safety assessments for up to 24 months. Data cut-off was 5/16/24 for this analysis, (up to 15 months of follow up) in the ongoing study.

251 and 165 subjects from MUIR and SHASTA-2 entered the extension in which all received plozasiran 25 mg SQ dosed quarterly. 10, 25 or 50 mg of plozasiran under blinded conditions produced mean reductions in TGs of -52 to -64% (MUIR) and -69 to -74% (SHASTA-2), 12 weeks (trough) after the second dose. Corresponding trough reductions in the extension ranged from -44 to -73% (MUIR) and -62 to -86% (SHASTA-2) through 15 months follow-up. Common reported AEs were consistent with the index studies and patient populations and mean HbA1c did not increase, providing further evidence that long-term safety remains favorable with repeated dosing and longer observation periods.

Extended open-label treatment with plozasiran in subjects with moderate to severely elevated TGs continue to show reductions of TG levels and safety consistent with the blinded index studies, demonstrating incidence rate and severity of TEAEs remain favorable with repeated dosing and longer observation. Results of additional lipid and lipoprotein parameters are also consistent with the blinded index data and will also be reported.
Abstract 4139853: Altering Cardiovascular Mortality in HFpEF with SGLT2i or ARNI — A Head-to-Head Analysis
Authors: Hariyanto Jesslyn , Veera Chirag , Lenzi Pinto Manoela , Chatterjee Anoushka , Eltawansy Sherif
Published: November 2024

Background:
Therapeutic options for HFpEF are continuously evolving. The latest AHA guidelines recommend ARNI with a class 2B and SGLT2i with a class 2A for HFpEF. Trials indicate that both SGLT2i and ARNI can improve clinical outcomes, but the practical implications of these costly novel agents must be considered. In this study, we assessed the effects of ARNI and SGLT2 inhibitors on cardiovascular mortality in HFpEF patients.

Methods:
PubMed, Scopus, and Cochrane search identified RCTs comparing ARNI with Valsartan, ACEi, or placebo, and SGLT2i with placebo. The outcome was cardiovascular mortality, comparing ARNI and SGLT2i subgroups. Heterogeneity was assessed with I^2 statistics with a random-effects model.

Results:
We included 8 RCTs with 15212 patients. Four studies were included with 27.6% being females with an age range of 70.9 - 72.9 years. Follow-up ranged from 8 weeks to 41 months, and mean LVEF was 57.3 ± 8%. Pooled RR for cardiovascular mortality (0.71 [95% CI: 0.47-1.09], P = 0.11) indicated no significant reduction in risk, with moderate heterogeneity (I^2 = 48%, P = 0.12)

In four studies in the SGLT2i subgroup, the age range was 60 to 71.9 years, with an LVEF range of 45 - 61%, and 48.7% of the participants were female. One study found women were more likely to have EF >60% than EF ≤45%. Background medication of ARNI or RAAS inhibitors was continued. Follow-up time ranged from 26.2 months to 4.2 years. Pooled RR for cardiovascular mortality (0.94 [95% CI: 0.83-1.06], P = 0.30) showed no significant reduction in risk, with low heterogeneity (I^2 = 34%, P = 0.21)

Combining both ARNI and SGLT2i groups, the total number of patients was 15,212 for the treatment group and 12,426 for the control group. The overall pooled RR (0.91 [95% CI: 0.81-1.03], P = 0.13) suggested no significant difference in cardiovascular mortality, with low heterogeneity across all studies (I^2= 34%, P = 0.16) The test for subgroup differences between ARNI and SGLT2i was not significant (P = 0.22) with low heterogeneity (I^2 = 33.4%)

Conclusion:
In HFpEF, subgroup analysis showed no significant differences in cardiovascular mortality reduction between ARNI and SGLT2i. Further research should investigate additional clinical and functional endpoints, considering the cost-effectiveness of these treatments.
Abstract 4139876: Type of diet and the Dietary Antioxidant Index are related to Long-term Microvascular Endothelial Function in coronary patients: From the Cordioprev Study
Authors: Delgado Lista Francisco Javier , Quintana-Navarro Gracia M. , Estevez Delgado Carmen , Lopez-Moreno Alejandro , Alcala-Diaz Juan Francisco , Torres Peña José D. , Perez-Martinez Pablo , Lopez-Miranda Jose
Published: November 2024

Introduction:
It has been described that both skin and coronary microvascular dysfunction occur in coronary heart disease patients, being a critical pathogenesis of cardiovascular diseases, mainly driven by a reduced endothelium-derived relaxing factor nitric oxide availability, the main homeostatic antioxidant in microcirculation. Various dietary factors could modulate endothelial function. Our goal was to evaluate the relationship between nutrition and long-term microvascular endothelial function in patients in secondary cardiovascular prevention. To do this, we evaluated the consumption of two healthy diets (Mediterranean Diet and Low-fat diet) and the total antioxidant content of the diet.

Methods:
With an analytical, longitudinal, experimental, and retrospective design, this work included all patients from the Cordioprev study who had completed endothelial function measures and dietary evaluations at the start of the study and after six years of intervention (n=520). Endothelial function (basal flow and area of reactive hyperemia) was measured using laser-Doppler flowmetry in the second phalanx of the third finger of the dominant hand. Food intake was evaluated using a food frequency questionnaire and the antioxidant quality of the diet using the dietary antioxidant index.

Results:
In the entire population, we observed a significant direct correlation between the evolution of the dietary antioxidant index and basal flow after 6 years of dietary intervention (p=0.024). When we studied the effect of the two diets investigated, in the Mediterranean diet group, an increase in the average dietary antioxidant index score was observed at the end of the study, and a direct relationship was also found between the dietary antioxidant index and endothelial function markers (basal flow (p=0.037); area of reactive hyperemia (p=0.015)). These findings were not observed after the low-fat diet.

Conclusions:
Our study indicates that, after six years of dietary intervention, changes in the total antioxidant content of the diet are directly correlated with changes in microvascular endothelial function in patients with coronary disease. These findings are especially evident with the Mediterranean Diet.
Abstract 4139904: Trends in Atrial Fibrillation Related Mortality in Metabolic Syndrome Patients Aged 65 and Older in the United States: Insights from the CDC WONDER Database
Authors: Naveed Muhammad Abdullah , Azeem Bazil , Omer Rehan Muhammad , Ali Ahila , Iqbal Rabia , Akbar Usman , Khan Muhammad , Gonuguntla Karthik , sattar yasar , Asad Zain Ul Abideen , balla sudarshan , Munir Bilal
Published: November 2024

Background:
Atrial Fibrillation (AF) in patients with metabolic syndrome is a substantial health concern among older adults in the United States. This study investigated trends and disparities in AF mortality among older adults aged 65 and older with metabolic syndrome from 1999-2020.

Methods:
We used the Centers for Disease Control database for mortality statistics with an underlying cause of death of AF in metabolic syndrome (ICD code I48 for AF and scattered codes indicating metabolic syndrome i.e. E10-14, E66, E78, E88, I10) between the years 1999 – 2020. Age-adjusted mortality rates (AAMR) were calculated per 100,000 deaths. The AAMR were assessed by demographic variables, including race, geographic density, sex, age, and US Census Region. Temporal trends were evaluated using Joinpoint regression software. Average annual percent change (AAPC) was considered statistically significant if p < 0.05.

Results:
Between 1999 and 2020, AF in metabolic syndrome caused 944,960 deaths among U.S. adults aged 65+. Most deaths occurred in medical facilities (35.8%). The overall AAMR for AF in metabolic syndrome-related deaths rose from 36.6 in 1999 to 173.4 in 2020, with an AAPC of 6.48 (95% CI: 5.07 to 7.77, p < 0.000001). A significant increase was noted from 1999 to 2001 (APC: 26.58; 95% CI: 6.04 to 43.91, p < 0.000001), followed by a continued rise from 2001 to 2020 (APC: 4.56; 95% CI: 3.60 to 5.15, p = 0.012797). Older men had higher AAMRs than older women (116.0 vs 92.3). Among racial/ethnic groups, White population had the highest AAMRs (108.8) and AAPC (6.70; 95% CI: 5.23 to 7.95), followed by American Indians/Alaska Natives (81.7), Blacks (74.1), Hispanics (68.2), and Asians (61.6). AAMRs varied by state, from 61.1 in Nevada to 170.0 in Vermont. The Western region had the highest average AAMR (116.7). Nonmetropolitan areas had slightly higher AAMRs than metropolitan areas (113.0 vs. 99.9).

Conclusion:
The analysis reveals a dramatic fourfold increase in AF-related mortality within metabolic syndrome among older U.S. adults over two decades. This substantial rise in mortality rates underscores the urgent need for targeted interventions and strategies to address these trends. By addressing structural barriers to quality healthcare and health disparities, we can effectively counter this concerning trend and achieve positive outcomes for this vulnerable group.
Abstract 4139931: Multidisciplinary Care Coordination Between Cardiologists and Neurologists Improves Outcomes for Patients with Hereditary Transthyretin Amyloidosis with Polyneuropathy: Results of a Quality Improvement Initiative
Authors: Khouri Michel , Zyborowicz Emily , Morgan Jennifer , Carter Jeffrey , Heggen Cherilyn
Published: November 2024

Background:
Patients with hereditary transthyretin amyloidosis (ATTRv) are often referred to amyloidosis centers for manifest cardiac symptoms and treated accordingly for transthyretin amyloid cardiomyopathy (ATTR-CM). However, emerging evidence suggests that many patients with variants traditionally associated with ATTR-CM also have polyneuropathic symptoms but often do not undergo comprehensive neurological evaluation and management that could prevent irreversible disease progression and improve quality of life.

Research Question:
What are the root causes of suboptimal multidisciplinary care that contribute to delayed diagnosis and comprehensive management of cardiomyopathy (CM) and polyneuropathy (PN) associated with ATTRv?

Goals:
The objective of this program was to improve multidisciplinary care from cardiology and neurology teams for patients with ATTRv.

Methods:
Cardiologists and neurologists from three amyloidosis centers engaged in two focus groups, completed surveys, and collected patient chart audits to evaluate their baseline ATTRv management processes and clinical workflows. During audit-feedback sessions, care teams analyzed their performance data and designed action plans to close gaps with the highest potential to improve patient outcomes.

Results:
Provider surveys (N=30) reported only 13% of institutions had referral protocols for neurologic workup of ATTRv, and 51% of providers were neutral or felt care coordination was ineffective. Similarly, data from patient charts (N=151) showed only 10% of patients completed PN screening to confirm diagnosis. During post-focus group participation, cardiologists exhibited heightened commitment to refer newly diagnosed patients to neurologists (39% to 76%) and to communicate with treating neurologists on disease status (44% to 76%). Although provider surveys showed 100% of patients are seen at least every 6 months, <5% received screening for emergent or progressive PN disease, whereas approximately 70% received CM screening. Identified gaps prompted practice changing initiatives including an improved intake process with PN screening and EMG referral, enhanced multidisciplinary collaboration to improve referral networks, and educational materials to heighten disease awareness.

Conclusion:
Practical strategies can be adopted by amyloidosis centers to ensure patients with ATTRv receive a comprehensive phenotypic workup and treatment through multidisciplinary collaboration between cardiologists and neurologists.
Abstract 4139955: Electronic Frailty Index as a Predictor of Clinical Outcomes in Older Adults with Myocardial Infarction
Authors: Pruitt Zachary , Ononye Chuka , Kleinsmith Allison , Doherty Sean , richardson karl
Published: November 2024

Background:
Myocardial infarction (MI) is a leading cause of mortality worldwide, and adverse outcomes among hospitalized patients are notable, particularly among older patients who experience frailty. Frailty is characterized by poor physiologic reserve and often results in poor response to medical insults. This study aims to assess the utility of a health record-based Electronic Frailty Index (eFI) in predicting clinical outcomes among these patients.

Methods:
This study is a single-center, retrospective cohort study of 390 patients aged 65 and older admitted with MI from October 2017 to January 2021. Data was collected using the ACC Chest Pain-MI registry and the electronic health record. Patients were divided into two cohorts: Fit (eFI <0.1) and Not Fit (eFI ≥0.1). Data was analyzed using descriptive statistics and multivariate nominal logistic regression. The primary outcome was in-hospital mortality. Secondary outcomes included revascularization strategy, Major Adverse Cardiac Events (MACE), adverse bleeding, development of cardiogenic shock, need for mechanical circulatory support, hospital length of stay, and discharge destination.

Results:
The mean age and standard deviation (SD) of the study cohort was 75 ± 6.97 years, with 130 (33%) females, 334 (86%) Caucasians, and 292 (75%) designated as Not Fit. Not Fit patients had a higher frequency of comorbid disease than Fit patients (Table 1). In-hospital mortality was significantly greater among Not Fit patients (8 vs. 2%, p = 0.03). Not-fit patients were more likely to be discharged to a hospice facility (6 vs. 1%, p = 0.05). Fit patients were more likely to undergo surgical revascularization (28 vs. 17%, p = 0.02). Additional secondary outcomes did not differ significantly between groups. A multivariate nominal logistic regression found that the patient’s Fit status (p = 0.03) and age (p = 0.05) were significant drivers of in-hospital mortality.

Conclusion:
Among patients admitted with MI, Not Fit patients had a greater likelihood of in-hospital mortality. Age and Fit status drove this association significantly, suggesting that lower physiologic reserve may lead to poorer clinical outcomes. Further study is needed to better characterize eFI as a risk-stratification tool for older patients with MI.
Abstract 4139960: AI-Derived Retinal Vasculature Features Predict Cardiovascular Risk in Patients with Chronic Kidney Disease: Insights from the CRIC Study
Authors: Dhamdhere Rohan , Modanwal Gourav , Rahman Mahboob , Al-Kindi Sadeer , Madabhushi Anant
Published: November 2024

Background:
Chronic kidney disease (CKD) is associated with increased risk of cardiovascular disease (CVD) and mortality. Fundus imaging offers a non-invasive method for CVD risk stratification through insights into microvascular disease.

Hypothesis:
Artificial-intelligence (AI)-derived retinal microvascular architecture predicts major adverse cardiovascular events (MACE) in CKD patients.

Objectives:
To determine the associations between retinal vessel features and CVD risk, and to compare AI derived retinal vessel-based CVD risk with existing CVD risk calculators for CKD patients.

Methods:
We analyzed retinal fundus images from 811 CKD patients without prior CVD or end-stage renal disease from the Chronic Renal Insufficiency Cohort (CRIC, NCT00304148). Vessels were segmented and classified into arteries and veins using deep learning models. CVD risk models were developed by extracting features like angle, tortuosity, curvature, and connectivity (Fig. 1A). Cox proportional hazards models were trained with features from Vessel (M
Ves
), Artery (M
A
), and Vein (M
V
). Models were trained using the top 8 features, selected via bootstrapping from 567 patients (70%) and validated on a holdout set of 244 (30%). Performance was evaluated using the concordance index (C-Index), hazard ratios (HR), and Kaplan-Meier (KM) curves. Feature models were compared with each other and the Framingham risk score (FRS) using the Likelihood ratio test (L.R.T.)

Results:
On the validation set of 244 patients, the risk score based on M
A
achieved a C-index of 0.69 (> vs < median risk, HR=3.79, 95% CI: 2.17-6.61). M
Ves
were comparable, with a C-index of 0.66 (HR=7.57, 95% CI: 2.63-21.76). M
V
had lower C-index and HR values. M
A
outperformed the FRS calculator (C-index=0.66, P<0.01). The M
A
risk score was associated with MACE, independently of FRS. This suggests retinal artery features, capturing angle, connectivity, and tortuosity, encapsulate novel information not captured by FRS variables (Fig. 1B).

Conclusion:
AI-derived retinal artery features were strongly associated with, and predictive of, MACE in CKD patients, independently of established clinical risk scores. Further multi-site prospective validation is required.
Abstract 4139976: Efficacy of High-Power Short-Duration Ablation on Epicardial Conduction Gap Following Pulmonary Vein Isolation and Carina Ablation, and Utility of High Unipolar-voltage-areas at the Carina as Indicators of Epicardial Connection Sites.
Authors: Kamioka Masashi , Watanabe Tomonori , Makimoto Hisaki , Watanabe Hiroaki , Okuyama Takafumi , Yokota Ayako , Komori Takahiro , Kabutoya Tomoyuki , Imai Yasushi , Kario Kazuomi
Published: November 2024

Introduction:
In pulmonary vein isolation (PVI), the carina is often refractory to ablation and require linear ablation, and some patients have epicardial connections.

Hypothesis:
High-power Shor-duration (HP-SD) ablation can prevent gap formation, and high unipolar-voltage-area (HUV), defined >2.7 mV, will identify the epicardial connection site.

Aims:
To investigate the impact of HP-SD ablation on durable PVI and the efficacy of HUV for the prediction of epicardial connection site.

Methods:
Ninety-three atrial fibrillation (AF) patients who underwent successful PVI were enrolled. Forty-one patients underwent HP-SD ablation, while fifty-two patients underwent conventional ablation. First pass isolation was achieved in 66 patients, while the remaining 27 patients needed carina ablation. The epicardial conduction gap (EG) of the PVI line was defined as the continuous propagation pattern across the PVI line under the high right atrial pacing. The epicardial connection (EC) was defined that the propagation pattern was defined as a centrifugal pattern with the earliest site located around the mid-carina, more than 5 mm far from PVI line.

Results:
Carina ablation following PVI was needed more frequently in conventional ablation group than in HP-SD group (38% vs. 17%, P = 0.020). However, there was no statistical difference in EC between HP-SD and conventional ablation groups ［2 of 41 (4.8%) in HP-SD vs. 3 of 52 (5.7%) in conventional, P = 0.852］. This suggests that HP-SD ablation could suppress EG formation more effectively. Among the 5 patients with EC, 4 patients (80%) had HUV adjacent to the earliest activation site at the mid-carina (3 in right and 1 in left). Notably, the EC was eliminated by ablation at the HUV but not at the earliest activation site. During a one-year follow-up, 7 patients experienced AF recurrence. Patients who underwent HP-SD ablation showed lower tendency for recurrence compared to those with conventional ablation (4.8% vs 13.4%, P = 0.126). Notably, no patients who underwent EC ablation in the HP-SD ablation group experienced recurrence, whereas all patients in the conventional ablation group experienced recurrence (0% vs 100%). Among patients requiring carina ablation, 1 of 2 in the HP-SD group and 6 of 7 in the conventional group experienced recurrence (50% vs. 85.7%).

Conclusion:
HP-SD ablation was effective to prevent EG and EC, and HUV was useful indicator of epicardial breakthrough site to endocardium.