bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 4140019: Emergency or Non-referral Admission Was Associated with Poor Outcomes in Adults Hospitalized for the Treatment of Cardiovascular Comorbidities in Congenital Heart Diseases: Analysis of the Nationwide Claim-based Dataset from The Japanese Registry of all Cardiac and Vascular Diseases-Diagnosis Procedure Combination
Authors: Mitani Yoshihide , Nakai Michikazu , Shiraishi Isao
Published: November 2024

Introduction:
The number of adults with congenital heart diseases (CHD) is rapidly increasing, who are frequently associated with cardiovascular morbidities and may result in poor outcomes. However, limited information is available regarding the current demographic status and the prognostic factors of adults hospitalized for the treatment of such patients on a nationwide scale. Hypothesis: We hypothesize that the prevalence of such CHD patients may increase with age in adulthood and that indices of loss to follow-up, emergency or non-referral admission, are related to poor outcomes.

Methods:
Using a nationwide claim-based dataset from Japan, we analyzed adult patients (aged 15 and over) with CHD diagnosed according to the ICD10 codes, who were hospitalized for the treatment of cardiovascular comorbidities between April 2013 and March 2022. Treatment groups included the surgery group and the catheter intervention (PCI) group for CHD or coronary revascularization and an ‘others’ group (patients treated for heart failure, infectious endocarditis or brain abscess), excluding those in the other two groups. CHD diagnosis was made based on the ICD-10 codes, while treatment categorization was made using specific procedure codes.

Results:
The study comprised 27,754 patients (male 49%), with a median age of 59 years (36-74) displaying bimodal peaks at <20 yo and 65-84 yo, and a body mass index of 21.6 (19.2-24.4). They were divided into 3 groups: surgery (n=8,800) (CHD surgery, n=8343; coronary bypass, n=457), PCI (n=3060) (CHD PCI, n=1998; coronary PCI, n=1062) and others (n=15,894) (heart failure, 96.9%). Underlying CHD by severity was categorized into simple (60.72%), intermediate (23.23%) and complex(9.44%) types. The overall patient cohort had emergency admissions (35.2%) and non-referral admissions (9.9%). Outcome measures included total hospital deaths (5.0%). In multivariate analysis, higher age, non-adult CHD center admission, CHD severity (intermediate or complex), emergency and non-referral admissions in the overall and the ‘others’ group correlated with hospital death (p<.001). The former 3 indices were independently associated with the latter 2 indices (p<.001).

Conclusions:
These findings demonstrated that higher age, underlying CHD severity, hospitals for admission, and indices of loss of follow-up were associated with poor outcomes. These findings underscore the importance of healthcare transition and CHD awareness in optimizing the outcomes.
Abstract 4140034: Orthostatic Pulse Pressure, A Novel Indicator of Preload Insufficiency, May Predict Clinical Response to SGLT2 Inhibition in HFpEF:
Findings from the PRESERVED-HF Trial
Authors: Yaku Hidenori , Sauer Andrew , Patel Shachi , Keefe Evan , Borlaug Barry , Kitzman Dalane , Windsor Sheryl , Khumri Taiyeb , Umpierrez Guillermo , Kosiborod Mikhail , Shah Sanjiv
Published: November 2024

Introduction:
Preload insufficiency can mimic HFpEF or complicate its treatment, and SGLT2 inhibitors may worsen preload insufficiency by reducing stressed blood volume. A drop in pulse pressure (PP) when going from supine to standing (i.e., orthostatic PP) may indicate an inability to vasoconstrict the splanchnic circulation, leading to preload insufficiency. We, therefore, sought to determine baseline characteristics associated with orthostatic PP and whether the effects of dapagliflozin vary by baseline orthostatic PP in patients with HFpEF.

Hypothesis:
In patients with HFpEF, the magnitude of treatment response to dapagliflozin – in terms of efficacy and safety - may be associated with orthostatic PP at baseline.

Methods:
We measured orthostatic PP (standing PP – supine PP) at baseline in 321 of the 324 patients with HFpEF randomized in the PRESERVED-HF trial. We categorized patients into tertiles of orthostatic PP and compared baseline characteristics. We examined the interaction between baseline orthostatic PP, treatment, and the following outcomes during 12 weeks of follow-up: (1) Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS); (2) 6-minute walk distance (6MWD); (3) volume depletion events.

Results:
At baseline, the median orthostatic PP was 0 mmHg (25
th
-75
th
percentile, -8.0, +5.3 mmHg). Patients with lower orthostatic PP had higher supine SBP and lower standing SBP. There were no differences in age, comorbidities, laboratory studies, KCCQ, and 6MWD among tertiles of orthostatic PP. Dapagliflozin improved KCCQ-CSS and 6MWD across the range of orthostatic PP; participants with the highest (vs lowest) orthostatic PP appeared to have numerically greater improvements with dapagliflozin, but these differences were not statistically significant (Table). Overall, 18 (5.6%) experienced volume depletion events (dapagliflozin 11 [6.8%], placebo 7 [4.3%]). In tertile 1 (lowest orthostatic PP), there were numerically more volume depletion events with dapagliflozin than placebo (8 [14.3%] vs 3 [5.0%] events); whereas the numbers of such events were similar in tertiles 2 and 3 (Table).

Conclusions:
In patients with HFpEF, dapagliflozin improved KCCQ and 6MWD across the range of orthostatic PP, although those with the highest (vs lowest) orthostatic PP appeared to have numerically greater improvements. Very low orthostatic PP may identify patients who could be at increased risk of volume depletion events with SGLT2 inhibitors.
Abstract 4140036: Long-term Prognosis of Acute Coronary Syndrome Patients with Mildly Reduced Ejection Fraction Following Emergency Percutaneous Coronary Intervention
Authors: Hagiwara Hikaru , Okamoto Takuro , OTSUBO KOTOMI , Katano Rui , Komoriyama Hirokazu , Kato Yoshiya , Anzai Toshihisa
Published: November 2024

Background:
Heart failure with reduced ejection fraction (HFrEF), defined as a left ventricular ejection fraction (LVEF) of <40%, after acute coronary syndrome (ACS) is associated with increased mortality rates. However, the long-term prognostic impact of HF in patients with mildly reduced EF (HFmrEF), defined as a LVEF of 40–49%, who undergo primary percutaneous coronary intervention (PCI) remains unclear.

Hypothesis:
Patients with HFmrEF have a better prognosis than those with HFrEF and a worse prognosis than patients with HF with preserved EF (HFpEF), defined as a LVEF of ≥ 50%.

Aims:
We compared the long-term prognosis among HFpEF, HFmrEF, and HFrEF patients.

Methods:
A total of 836 consecutive ACS patients who underwent emergency PCI at our hospital between April 2014 and March 2024 were retrospectively recruited. We compared all-cause mortality and adverse cardiovascular events, including cardiac death and heart failure hospitalization. Patients were divided into three groups based on LVEF assessed by echocardiography within 1 month after PCI: HFpEF, HFmrEF, and HFrEF.

Results:
After excluding 117 patients who lacked echocardiographic data, 719 patients were included (HFpEF, 443; HFmrEF, 180; HFrEF, 96). Patients with lower EF were older and had higher plasma brain natriuretic peptide levels at admission. During a median follow-up period of 3.8 years (interquartile range: 1.5–6.3), 105 patients (13%) died. Patients with lower EF had a higher incidence of all-cause mortality and adverse cardiovascular events (
Figure
). Multivariate analysis indicated no difference in all-cause mortality between HFrEF and HFmrEF groups (adjusted hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.44–2.60), although adverse cardiovascular events were significantly different (adjusted HR 0.44, 95% CI 0.24–0.82). On the other hand, there was no difference in all-cause mortality between HFmrEF and HFpEF groups (adjusted HR 0.49, 95% CI 0.31–0.79), although adverse cardiovascular events were significantly different (adjusted HR 0.35, 95% CI 0.18–0.69).

Conclusion:
In patients with ACS following emergency PCI, HFmrEF is associated with a better prognosis compared with HFrEF, but with a worse prognosis than HFpEF.
Abstract 4140042: Impact of Inflammatory and Insulin Resistance Biomarkers on Long-Term Risks in Coronary Heart Disease Patients with Cardiovascular-Kidney-Metabolic Syndrome
Authors: Zhang Kexin , Li Jiawen , Li Yulong , Yan Kailun , Zhao Xueyan
Published: November 2024

Background:
Abundant evidence has suggested that individuals with poor Cardiovascular-kidney-metabolic (CKM) health are at a heightened risk of adverse cardiovascular events. In patients with coronary heart disease, a considerable proportion has concurrent CKM, which warrants further attention.

Purpose:
This study aimed to evaluate the prognostic significance of inflammatory and non-insulin-based insulin resistance biomarkers in patients with confirmed CHD and CKM syndrome.

Methods:
Among 10724 consecutive patients admitted to our center for CHD in 2013, 9716 patients who met the diagnostic criteria for CKM syndrome were included in this study. The endpoint was the major cardiac and cerebrovascular event (MACCE). The optimal cut-offs of the indicators were determined by the receiver operating characteristic analysis.

Results:
During a median follow-up of 5.05 years, 2019 cases of MACCEs were observed. At baseline, the mean age of the overall cohort was 58.4 ± 10.3 years, and 7467 (76.9%) patients were male. Multivariable Cox regression analysis revealed that elevation of any inflammatory biomarkers levels [including white blood cells, neutrophils, monocytes, platelets, neutrophil-to-platelet ratio, neutrophil-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory response index, systemic inflammatory index, pan-immune-inflammation value (PIV) and high-sensitivity C-reactive protein] was significantly associated with an increased risk of 5-year MACCE (all
P
<0.05), while PIV demonstrated the relatively strongest association [hazard ratio (HR) 1.274, 95% Confidence Interval (CI) 1.161-1.397;
P
<0.001]. However, among the indicators of insulin resistance [including the triglyceride and glucose (TyG) index, TyG-body mass index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) and metabolic score for insulin resistance], only TG/HDL-C remained significant after adjusting for confounding factors, with a HR of 1.147 (95% CI 1.027-1.280; P<0.05).

Conclusions:
This current study reveals that, multiple inflammatory biomarkers and TG/HDL-C have predictive significance for the long-term prognosis of CHD patients with CKM syndrome, suggesting the potential application of these indicators in the assessment among the high-risk population. Further investigation is warranted to determine whether targeted treatment of these biomarkers would be of benefit.
Abstract 4140051: Healthcare utilization trends for adolescents and young adults with moderate and severe congenital heart disease
Authors: Yatsenko Victoria , Mathena Sarah , Andrews Jennifer , barber brent , Hoyer Andrew , Fox Kenneth , Meziab Omar , Guerrero Claudia , Klewer Scott , Seckeler Michael
Published: November 2024

Background:
Improved congenital heart disease (CHD) care allows >90% of patients to live into adulthood, but young adult CHD patients are challenged by managing their own care as well as the risk of other comorbidities that may increase healthcare resource utilization. There is limited data on hospitalizations of adolescents with CHD, specifically during the transition from pediatric to adult care.

Hypothesis:
We hypothesized that as adolescents age into adult care, utilization of healthcare resources will increase.

Methods:
We conducted a retrospective review of the Vizient® Clinical Data Base (national, administrative database) for admissions from 10/2019-12/2023 aged 10-29 years with ICD-10 codes for moderate or severe CHD and stratified into age categories (10-14, 15-19, 20-24 and 25-29 years). Data included: demographics, hospital outcomes, insurance status, costs and admissions through the Emergency Department (ED). Comparisons were made using ANOVA for normally distributed data and χ
2
for categorical data; Bonferroni test was used for post-hoc analysis. A
p
-value <0.05 was considered significant.

Results:
There were 16,284 admissions during the study period; details in Table 1. With increasing age, there was an increase in female admissions, an increasing prevalence of Whites individuals and decreasing prevalence of Hispanic individuals. There was a decrease in public insurance and an increase in uninsured status and ED admissions with increasing age. Complications increased between 10-14 to 25-29 years old. Mortality rates had peaks at 15-19 years old and 25-29 years old. Despite increased ED visits, complications and mortality, costs decreased between the younger age groups and older age groups.

Conclusions:
There is an increase in uninsured status and ED admissions for hospitalized young adults transitioning from pediatric to adult care. Despite this trend, overall hospital costs decrease, which may be due to more procedural admissions in children and adolescents. More studies are needed to help guide improvements in care during this at-risk time.
Abstract 4140053: Effect of Sacubitril/Valsartan in Patients with Concomitant Heart Failure with Reduced Ejection Fraction and End-Stage Renal Disease on Hemodialysis
Authors: Ahn Yuran , Jung Mi-Hyang , Youn Jong-Chan , Cho Dong-Hyuk , Choi Jimi , Yoo Byung-Su
Published: November 2024

Aims:
This study aimed to explore the comparative effectiveness of sacubitril/valsartan (SV) to renin-angiotensin system (RAS) blockade in patients with concomitant heart failure with reduced ejection fraction (HFrEF) and end-stage renal disease (ESRD) on hemodialysis.

Method:
We enrolled patients with HFrEF and ESRD on hemodialysis using data from the Korean National Health Insurance Service data (2017–2021) covering the entire national population. A total of 2,248 patients with HFrEF who received SV were compared with 2,528 patients with HFrEF who received RAS blockade by inverse probability treatment weights. The primary endpoint was a 2-year composite outcome of all-cause mortality or any hospitalization. Differential effects according to medication adherence were also analyzed using proportion of days covered (PDC).

Results:
SV reduced the risk of the primary outcome compared to the RAS blockade group (hazard ratio [HR] 0.85, 95% confidence interval [CI] 0.75–0.96,
P
= 0.009). SV significantly reduced all-cause mortality (HR 0.74; 95% CI 0.59-0.93,
P
= 0.008) and any hospitalization (HR 0.85; 95% CI 0.75-0.95,
P
= 0.007). In the group with a PDC ≥80%, SV reduced the risk of all-cause, cardiovascular mortality and any hospitalization than RAS blockade (all-cause mortality, HR 0.61; 95% CI 0.46–0.80;
P
<0.001, cardiovascular mortality, HR 0.59; 95% CI 0.43-0.82,
P
= 0.001, any hospitalization, HR 0.80; 95% CI 0.80-0.94,
P
= 0.007).

Conclusions:
In a real-world population with concomitant HFrEF and ESRD on hemodialysis, SV significantly reduced the risk of all-cause mortality and any hospitalization compared to the RAS blockade. These benefits were more definite in a subpopulation with a PDC ≥ 80%, suggesting the importance of medication adherence in improving cardiovascular outcomes.
Abstract 4140069: Improvement in left and right ventricular function in heart failure patients with reduced ejection fraction initiated or continued on angiotensin receptor neprilysin inhibitors in a GDMT clinic
Authors: Orihara Yoshiyuki , Eguchi Shunsuke , Eguchi Ayumi , Pfeiffer Michael , Ali Omaima , Baksh Gladys , Reesor Heather , Haydo Michele , Wilson Ryan , Boehmer John , Gorcsan John , Farbaniec Michael
Published: November 2024

Background:
Initiation of Guideline-Directed Medical Therapy (GDMT) in patients who have heart failure with reduced ejection fraction (HFrEF) has been shown to improve left ventricular EF, decrease hospitalizations, and reduce mortality. GDMT includes an angiotensin receptor/neprilysin inhibitor (ARNI). However, the relative importance of initiating or maintaining ARNI therapy during titration of GDMT and the impact on changes in left ventricular (LV) and right ventricular (RV) function is unknown.

Methods:
We enrolled 173 patients with HF in a GDMT clinic prospectively between 2020 to 2022. Of 173 patients, 63 HFrEF patients with baseline and 3-12 months follow-up transthoracic echocardiography (TTE) were included in this post-hoc analysis. Patients were divided into three groups; patients with initiation of ARNI after baseline TTE (Group 1), patients with continuation of ARNI that was started before baseline TTE (Group 2), patient who were not on ARNI during evaluation period (Group 3). LVEF as calculated by volumetric assessment, LV global longitudinal strain (LVGLS), RV fraction area change (RVFAC), and RV global longitudinal strain (RVGLS) were evaluated in this study. Strain analysis of LVGLS and RVGLS were applied using TomTec.

Results:
The mean age was 64 years, the mean time between TTEs was 6.9 months. Improvement in biventricular function and strain were noted between baseline and follow up data. (Figure 1) Changes of the four parameters for each group between the two TTEs are shown in Figure 2. In patients initiated on ARNI therapy (Group 1) there was a significant improvement from baseline to follow up TTEs in all parameters. (LVEF; p < 0.001, LVGLS; p < 0.001, RVFAC; p = 0.003, and RVGLS; p = 0.003) In group 2, we noted significant improvements in LVEF, LVGLS, and RVGLS from baseline to follow up. (LVEF; p < 0.001, LVGLS; p < 0.001, and RVGLS; p = 0.005) In those not on ARNI (Group 3), there was no statistical difference noted in any of the 4 parameters between baseline and follow up TTE.

Conclusion:
In patients with HFrEF, who had routing follow-up in a GDMT clinic, those initiated or continued on ARNI had significant improvement in biventricular function and biventricular strain measurements, compared to those who were not taking an ARNI.
Abstract 4140073: Impact of Myosin S2 and cMyBP-C Interaction on Cardiac Contractility in Hypertrophic Cardiomyopathy
Authors: Maguire Megan , Green Lisa , Singh Rohit , Ason Brandon , Nieman Michelle , Koch Sheryl , Gong Henry , Lorenz John , Rubinstein Jack , Kirk Jonathan , Burton Aaron , Sadayappan Sakthivel
Published: November 2024

Background:
Cardiac muscle contraction and relaxation are regulated by the interaction between myosin neck region (S2) and cardiac myosin binding protein-C (cMyBP-C). Clinically, several mutations in the myosin S2 region, affecting its interaction with cMyBP-C, have been linked to hypertrophic cardiomyopathy (HCM). However, the molecular mechanism by which mutations in myosin S2 affect function is unknown. The interaction of the myosin S2 region with cMyBP-C and whether facilitating this interaction using a small peptide of myosin S2 can efficiently improve cardiac contractility remains unclear.

Objectives:
To determine the interactive region of myosin S2 with cMyBP-C on contractility
in vitro,
and define the impact of an E932del mutation in α-myosin (Myh6E932del)
in vivo
, which is located in the myosin S2 region affecting its interaction with cMyBP-C.

Methods and Results:
To target the cMyBP-C-myosin interaction, we used the proximal region of S2 (126aa) and nine overlapping and shortened variations of the S2 region in solid-phase binding and skinned papillary muscle assays. Based on these experiments, we determined that Amg 27119, a 22-amino acid myopeptide, was highly efficacious in improving contractile function in cardiac muscle. Next, we generated a CRISPR-Cas9 mediated knock-in mouse model expressing the Myh6E932del mutation. Echocardiography and real-time PCR data from heterozygous mice at 9 months of age revealed cardiac hypertrophy with preserved cardiac function and increased expression of cardiac hypertrophic genes compared to wild-type controls, respectively.
In vivo
catheterization analyses indicated impaired relaxation, with reductions in dP/dt
min
and tau in mutant mice versus controls. pCa-force measurements showed significantly increased force production in mutant skinned myocytes (29.289 nM/mm^2, p=0.0039) compared to controls (20.311 nM/mm^2), without affecting myofilament calcium sensitivity and the Hill coefficient.

Conclusion:
The myopeptide was determined to target and relieve the cMyBP-C inhibition of myosin, thereby improving contractility
in vitro
. Disrupting the interaction between myosin S2 and cMyBP-C with HCM mutations results in diastolic dysfunction and hypercontraction.
Abstract 4140078: Association of Extreme Heat with Cardiovascular and All-cause Emergency Department Visits in the United States
Authors: Szeto Jonathan , Shultz Kaitlyn , Bansal Esha , Puvvula Jagadeesh , Hennessy Sean , Chen Aimin , Khatana Sameed Ahmed
Published: November 2024

Background:
Extreme heat events have increased in frequency and intensity and are projected to continue increasing due to climate change. Extreme heat is associated with an increase in both all-cause and cardiovascular (CV) mortality. However, how extreme heat impacts CV disease related emergency department (ED) visits is not well studied.

Methods:
Data on all ED visits among adults 20 years and older from 16 US states in summer months (May through September) for 2010 to 2018 were obtained from State ED all-payer claims databases. After determining the monthly number of ED visits in each county, the county-level monthly number of extreme heat days was determined. Extreme heat days were defined as any day with a maximum heat index ≥90°F (32.2°C) and in the 97.5
th
percentile based on a county-specific historical period (1979-2007). CV ED visits were identified using ICD-10 diagnostic codes (I00-I99). A Poisson fixed effects regression model with county, year, and month fixed effects was estimated with monthly ED visits as the outcome and the monthly number of extreme heat days as the primary predictor of interest. Environmental, economic, and demographic variables were also included in the model. Excess ED visits were estimated as the difference between the number of visits, in each county, with the observed number of extreme heat days and the estimated number of visits if no extreme heat days had occurred.

Results:
There were approximately 91 million all-cause and 1.5 million CV ED visits across 985 counties during summer months in 2010 to 2018. The population-weighted, total median number of extreme heat days over the study period was 79 (IQR 63-98). From 2010-2018, each additional extreme heat day per month was associated with a 0.21% (95% CI 0.02-0.41,
p
=0.03) increase in monthly CV ED visits and a 0.20% (95% CI 0.06-0.35,
p
=0.006) increase in monthly all-cause ED visits. The estimated number of extreme heat associated excess CV ED visits over the study period was 5658.4 (95% CI 525.0-10791.9). The estimated number of excess all-cause ED visits was 329055.4 (95% CI 95625.4-562485.4)

Conclusion:
Extreme heat was associated with an increase in CV and all-cause ED visits in 16 states in the US between 2010 and 2018. As extreme heat events continue to increase, understanding how this will impact emergency departments and health systems across the country is important to be able to devise strategies to address the associated increase in utilization.
Abstract 4140079: Inhibition of AT1R Attenuates AML and Prevents Chemotherapy-induced Cardiotoxicity
Authors: Pan Yi , Wang Chen , Zhou Wenxuan , Meng Xiaduo , Shi Yao , Liu Zhenguo , Muhammad Yasir , Hammer Richard , Li De Pei , Kang Xunlei
Published: November 2024

Introduction:
Patients with acute myeloid leukemia (AML) frequently develop significant cardiac toxicity when receiving chemotherapy with poor prognosis, but the mechanisms remain largely unknown. Our in silico analysis revealed that angiotensin II receptor type 1 (AT1R) is abundantly expressed in AML and significantly increased in the blood of AML patients. It is known that AT1R is associated with the pathogenesis of cardiomyopathy.

Hypothesis:
We hypothesize that inhibiting AT1R can simultaneously suppress AML development and reduce chemotherapy-induced cardiotoxicity.

Methods and Results:
Inhibition of AT1R inhibition using specific AT1R inhibitor or AT1R knockout (KO) substantially reduced AML stemness and boosted chemotherapy efficacy for AML. Mechanistically, AT1R regulates γ-secretase activity, which is responsible for Notch1 transcription factor activation. AT1R KO effectively reduced the expressions of Notch1 downstream genes responsible for AML stemness, cell cycle,and proliferation. When Notch1 was re-introduced into AT1R KO AML cells, the expressions of these Notch1 downstream genes were rescued. Additionally, chromatin structure omics (HiC) and epigenetic omics (CUT&RUN)analysis revealed that 3D-chromatin structural and epigenetic alteration of multiple genes were associated with chemotherapy resistance. In fact, human AML patient derived xenograft model showedAT1R inhibition simultaneously boosted chemotherapy for AML while reducingchemotherapy-induced cardiotoxicity. Further mechanistic study demonstrated that the expression of angiotensin-converting enzyme was significantly increased in the cellsurface of AML with increased blood Ang II level in a mouse model, thus, may contributing to chemotherapy-induced cardiac toxicity.

Conclusions:
Together, these data demonstrated that AT1R-mediated signaling plays a key role in AML development and chemotherapy-induced cardiotoxicity. These findings indicate that the high incidence of cardiomyopathy in AML was increased AT1R-mediated signaling and targeting AT1R signaling could be a novel strategy for simultaneously suppressingleukemia, boosting chemotherapy efficacy, and preventing chemotherapy-inducedcardiotoxicity.
Abstract 4140082: Mediation of Higher Coronary Heart Disease Risk in Non-White Populations by Lifestyle-Psychosocial and Genetic Factors: A Comparative Analysis
Authors: Naderian Mohammadreza , Norland Kristjan , Kullo Iftikhar
Published: November 2024

Background:
Coronary heart disease (CHD) results from environmental and genetic factors. Lifestyle-psychosocial factors that capture environmental risk and polygenic risk scores (PRS) that capture genetic risk have been associated with CHD in prior studies.

Aim:
To assess whether higher CHD risk traditionally attributed to non-White race/ethnicty is mediated by PSS
CHD
or PRS
CHD
.

Methods:
In UK Biobank, we ascertained incident CHD (MI/coronary revascularization) and calculated an ancestry-specific PRS for CHD (PGS000018). Based on self-reported race/ethnicity, participants were classified as White and non-White. An age, sex, and ethnicity-adjusted polysocial score for CHD (PSS
CHD
) was derived from 100 self-reported lifestyle-psychosocial factors across nine domains: Adulthood Relationship, Education, Entertainment, Housing, Income, Occupation, Physical Activity, Psychological Health, and Sleep. Those with CHD or statin use at recruitment or missing age, sex, race/ethnicity or genotype were excluded. Machine learning (elastic net model) was used to develop PSS
CHD
. Cox and mediation analyses were performed.

Results:
In 398,403 participants (56±8 y, 43% male, 96.3% White, 1.8% Asian, 1.6% Black, and 0.3% Chinese), 10,033 had an incident CHD event during a 10-year follow-up. The HRs (95% CIs) for a 1 SD increase in PSS
CHD
and PRS
CHD
for CHD risk were 1.5 (1.4–1.5,
P
<10
-16
), and 1.6 (1.5 - 1.6,
P
<10
-16
), respectively (Figure 1A-B). Asians and Blacks had the highest PSS
CHD
(mean±SD: 0.5±1, and 0.5±1, respectively), followed by Chinese (0.1±0.9), and Whites (0.0±1) (Figure 1C). After adjustment for age, sex, diabetes, hypertension, LDL-C, and smoking, non-Whites had higher CHD risk: HR (95% CI): 1.2 (1.0–1.4,
P
<10
-16
), and the higher risk was mediated more substantially by PSS
CHD
than PRS
CHD
(63% (38%-100%) vs. 16% (8%-41%), both
P
<10
-16
).

Conclusions:
The higher CHD risk observed in non-Whites in UK Biobank was mainly due to unfavorable lifestyle-psychosocial factors, rather than PRS, consistent with the paradigm that race/ethnicity is not a biological but rather a social construct. Our findings support substituting race/ethnicity with lifestyle-psychosocial factors and social determinants of health in CHD risk equations.
Abstract 4140089: Lower low-lipoprotein cholesterol level at the time of acute myocardial infarction is associated with increased cardiovascular events
Authors: Onozato Takuya , Wada Hideki , Ogita Manabu , Abe Keiki , Singh Yu Suresvar , Shitara Jun , Suwa Satoru , Miyauchi Katsumi , Minamino Tohru
Published: November 2024

Background:
Lipid-lowering therapy for patients with acute myocardial infarction (AMI) is highly recommended, however, a paradox may exist where lower low-density lipoprotein cholesterol (LDL-C) levels at myocardial infarction (MI) are associated with poorer prognoses.

Aim:
To evaluate the association between baseline LDL-C levels and cardiovascular events after MI.

Methods:
We studied 1,987 consecutive AMI patients who underwent primary percutaneous coronary intervention and who had available data on preprocedural LDL-C between 1999-2015 at Juntendo University Shizuoka Hospital. Patients were divided into quartiles based on their LDL-C levels. The incidence of major adverse cardiac events (MACE), including all-cause death and recurrent MI up to 5-year, were evaluated.

Results:
Patients in the lowest LDL-C group were older and had higher prevalence of hypertension, diabetes mellitus and chronic kidney disease. During follow-up, 455 (20.9%) MACE were identified. Cumulative incidence of MACE was significantly higher in the lowest LDL-C group than in other groups (p<0.0001, Figure). After adjustment for other risk factors, the lowest LDL-C group had a significantly higher risk of MACE compared with the highest group (hazard ratio, 1.52; 95% confidence interval, 1.11-2.08; p=0.009). On the other hand, no significant difference in cardiovascular risk was found for patients in the highest LDL-C group compared to patients in the second or third groups.

Conclusions:
Lower LDL-C level was associated with worse clinical outcomes among patients with MI. Patients with lower LDL-C level have a poor prognosis and require more attention.
Abstract 4140201: Disparities in Defibrillator Implantations during COVID-19: Insights from the NCDR registry
Authors: Karim Saima , Lampert Rachel , kennedy kevin , Spertus John , He Beixin
Published: November 2024

Introduction:
While implantable cardiac defibrillators (ICD) decrease sudden cardiac death, disparities in ICD use remain. The COVID-19 pandemic created strains on the US healthcare system that may have exacerbated these disparities.

Methods:
Using the US NCDR registry of primary and secondary prevention ICD implants, we compared sex, racial and ethnic disparities for 239,014 patients, aged 19-90 years, grouped into three time intervals from 2016 to 2022: Pre-COVID, COVID and Post-COVID. Centers without consistent reporting were excluded, as were patients with incomplete sex, race or ethnicity data. ICD implantation rates were compared using a Poisson regression model with interaction tests for sex, race and ethnicity by time window to see if disparities changed within this period. Implant rates by indication were also assessed.

Results:
Overall ICD implants decreased over the study period (Figure 1) with an average monthly rate of 3271 in the first three months of 2016 declining to 2334 in the last three months of 2022 (p=0.017). Disparities in ICD implantation for women, racial and ethnic minorities were observed pre-COVID and persisted (Table 1). Average ICD implant rates during these time periods varied by race with predominance in White patients. While gaps in ICD implant persisted, the disparities did not worsen during COVID-19 by sex, race or ethnicity (p-value for interactions were 0.79; 0.47; and 0.095, respectively). There was a more significant decrease in primary prevention ICD compared to secondary prevention ICD (p<0.0001), but similarly, there was no significant interaction based on sex, race and ethnicity.

Conclusion:
Since COVID-19, a period of extreme healthcare rationing, overall ICD use decreased. Historical gaps in ICD implantation for women, racial and ethnic minorities persisted but did not increase. While it is encouraging that disparities did not worsen during a time of limited resources, there is an ongoing need for greater equity in ICD implantation.
Abstract 4140208: Predicting 30-Day and 1-Year Mortality in Heart Failure with Preserved Ejection Fraction (HFpEF) using Electronic Health Record Data
Authors: Shin Ikgyu , Bhatt Nilay , Alashi Alaa , Kandala Keervani , Murugiah Karthik
Published: November 2024

INTRODUCTION:
Heart failure with preserved ejection fraction (HFpEF) represents 50% of heart failure patients. Predictive models in HFpEF, specifically those derived from electronic health record (EHR) data, are less established.

HYPOTHESIS:
EHR models can predict 30-day and 1-year mortality in HFpEF patients. Machine learning (ML) models compared with traditional may show superior performance.

AIM:
Develop and compare prediction models for 30-day and 1-year mortality in HFpEF using EHR data, using traditional and ML techniques.

Methods:
Using MIMIC-IV data (EHR data from the Beth Israel Deaconess Medical Center in Boston) from 2008-2019, we identified patients aged ≥ 18 years admitted with a primary diagnosis of HFpEF using ICD-9 and 10 codes. Demographics, vital signs, prior diagnoses, and lab data were extracted. After preprocessing, data was partitioned into 70% training and 30% test. Prediction models from seven model classes were developed using a variety of imputation and oversampling techniques using 5-fold cross validation - Support Vector Classifier (SVC), Logistic Regression, Lasso Regression, Elastic Net, Random Forest, HistGradient Boosting Classifier, and XGBoost. Model performance was compared using several metrics. SHapley Additive exPlanations (SHAP) analysis was used to assess individual feature influence on model output.

Results:
Among 3910 individual hospitalizations for HFpEF the 30-day mortality was 6.3% and 1-year mortality was 29.2%. Performance metrics of the best model in each class is shown in Table 1. By AUCs, Lasso and Elastic Net Regression models provided superior prediction for 30-day mortality (AUCs of 0.79, each), whereas Random Forest and HistGradient Boosting Classifier for 1-year mortality (AUCs of 0.78 each). Overall, considering all metrics, Elastic Net and Lasso regression models gave a good combination of sensitivity, specificity and AUC enhancing their clinical applicability. SHAP analyses showed age, NT-proBNP and sodium levels, WBC, and platelet counts as key drivers of these predictions.

Conclusion:
Models derived from EHR data, which is important for implementability, predict mortality after HFpEF hospitalization with good performance comparable to models derived from registry or trial data.
Abstract 4140218: Trends and Determinants of Outcomes in STEMI Patients with COVID-19: A Nationwide Analysis, 2020-2021
Authors: Singh Rahul , Selvam Shalini , Ozga Dawid , Sukhoo-Pertab Marc , Toreli Aleksandre , Hegde Sudhanva
Published: November 2024

Background:
Prior data indicated a reduction in mortality among STEMI (ST-elevation myocardial infarction) patients with COVID-19 from 2020 to 2021 in the United States.

Objective:
To describe national trends and determinants of outcomes among STEMI patients with COVID-19 from 2020-2021.

Methods:
A retrospective cohort study was conducted using the 2020-2021 Nationwide Inpatient Sample of adults diagnosed with STEMI and COVID-19, assessing in-hospital mortality and the use of percutaneous coronary intervention (PCI), mechanical ventilation, and mechanical circulatory support (MCS).

Results:
The study included 6,195 STEMI patients with COVID-19 and revealed stable mortality (18% in 2020 to 21% in 2021,
p
=0.06). Demographic shifts occurred, with White patients increasing from 52% in 2020 to 66% in 2021 (
p
<0.01). Mechanical ventilation increased in 2021 (Adjusted Odds Ratio [aOR] 1.75;
p
<0.01).

Compared to White patients, 'Other' race patients had higher odds of mortality (aOR 2.46;
p
=0.01). Compared to Medicare beneficiaries, Medicaid recipients demonstrated a reduced risk of mortality (aOR 0.47;
p
=0.02), as did individuals residing in the highest income quartile zip codes compared to the lowest (aOR 0.54;
p
=0.03). Asian/Pacific Islander patients were less likely to receive PCI (aOR 0.43;
p
=0.03). Increased MCS was noted in Black (aOR 1.78;
p
=0.03), Hispanic (aOR 1.87;
p
=0.01), and 'Other' race patients (aOR 3.78;
p
<0.01).

Conclusion:
This study found no statistically significant change in mortality among STEMI patients with COVID-19 from 2020 to 2021. The findings highlight persistent challenges and the need to improve the equity and effectiveness of cardiac care.
Abstract 4140219: Performance of a Novel Rheumatic Heart Disease Screening Protocol Led by Non-Expert Frontline Nurses in Uganda
Authors: Wirth Scott , warren paul , Nakagaayi Doreen , Pulle Jafesi , Sable Craig , Okello Emmy , Watkins David , Danforth Kristen , Beaton Andrea
Published: November 2024

Background:
Poor healthcare access results in late- or non-diagnosis of rheumatic heart disease (RHD), perpetuating the burden of RHD in low-resource settings. The ADUNU program, a partnership with the Ugandan Ministry of Health in Kitgum, Uganda, aims to improve RHD case detection through decentralized screening led by primary care nurses, who independently perform and interpret brief screening echocardiograms using handheld echocardiography.

Hypothesis:
We hypothesized ADUNU’s simplified screening protocol would achieve sensitivity and specificity greater than 80% on confirmatory evaluation.

Aim:
To determine the health system impact of deploying a novel RHD screening protocol into the public health system in Uganda through a cross-sectional study of diagnostic accuracy.

Methods:
Primary healthcare nurses, certified to perform echocardiographic screening using a single parasternal long axis view in 2D and color Doppler, integrated screening into their clinical and outreach workflows. Community members with positive screens (mitral regurgitation jet ≥2cm or aortic regurgitation jet ≥1cm) were referred for confirmatory echocardiograms at the District Hospital. A random subset with negative screens were recruited for confirmatory echocardiograms at the time of screening as well. Sensitivity, specificity, predictive values, likelihood ratios, accuracy, and agreement (Cohen’s kappa) were calculated between the screening protocol and the confirmatory results.

Results:
Between May 2023 and April 2024, 3020 community screenings (ages 5-70 years) were conducted by 19 certified nurses. Among 113 positive screens, 61 (53.9%) were confirmed to have RHD. Among 430 negative screens, 14 (3.3%) had RHD. Screening sensitivity was 82.4% (95% CI 72.2-89.4%) and specificity 89.1% (85.9-91.6%). Positive and negative predictive values were 54.5% (45.2-63.4%) and 97.0% (94.9-98.2%). Likelihood ratios were 7.55(+) and 0.19(-). Accuracy was 88.3% (85.2 – 91.4%) and kappa was 0.59 (0.49-0.68).

Conclusions:
ADUNU’s novel approach to RHD active case finding achieved acceptable diagnostic performance. Nurse-led RHD screening programs that are integrated into routine clinical care shows potential for use in a comprehensive public health program. Very few RHD cases were missed, and under two referrals were generated for every positive case, an acceptable false positive rate. Further economic evaluation is underway to understand the budgetary impact and cost-effectiveness of this program.
Abstract 4140229: Hypertension Enhances the Impact of Lipoprotein (a) on Coronary Artery Calcification in Coronary Heart Disease Patients Undergoing Percutaneous Coronary Intervention
Authors: Li Yulong , Yan Kailun , Zhang Kexin , Yang Yue-Jin , Yuan Jinqing , Zhao Xueyan
Published: November 2024

Introduction:
Both lipoprotein (a) [Lp(a)] and hypertension have been identified as the independent risk factors for atherosclerotic cardiovascular diseases. Coronary artery calcification (CAC) is a highly specific marker of atherosclerosis. However, though the association of Lp(a) and CAC is controversial, the combined effect of hypertension and Lp(a) on CAC remains unclear.

Objective:
This study aimed to investigate the combined effect of hypertension and Lp(a) on CAC in coronary heart disease patients undergoing percutaneous coronary intervention (PCI).

Methods:
10,724 consecutive patients undergoing PCI in 2013 were enrolled. High Lp(a) level was defined as Lp(a)≥30mg/dl. Patients were divided into low-degree CAC group and high-degree CAC group according to the coronary angiography results. (Figure 1)

Results:
A total of 9,781 patients (mean age, 58.24 ± 10.30; male, 76.8%) who had both Lp(a) and CAC results were finally enrolled for analysis. Multivariate logistic regression analysis (Figure 2) showed that compared with patients without hypertension and high Lp(a), those with only high Lp(a) but without hypertension was not associated with high-degree CAC, which was same as in those with only hypertension but without high Lp(a) (all
P
>0.05). However, patients with both hypertension and high Lp(a) had significantly higher risk of high-degree CAC (OR=1.180, 95% CI=1.007-1.382,
P
=0.041). Moreover, age, diabetes and prior coronary artery bypass grafting were relevant risk factors of high-degree CAC (all
P
<0.05).

Conclusions:
In this large-scale real-world study, we reported for the first time that patients with both hypertension and high Lp(a) had significantly higher risk of high-degree CAC. In the future, whether targeting on both hypertension and Lp(a) could delay the progression of atherosclerosis and CAC deserves further investigation.
Abstract 4140237: Cardiac Magnetic Resonance Anatomic-derived Indices Better Predict Arrhythmia than Functional Parameters in Patients with Ebstein’s Anomaly
Authors: Urbina Thomas , Ochoa Andres , Torres Gomez Daniela , Villa Pallares Eduardo , Perez-Fernandez Oscar , Forero Julian Francisco , Acosta Izquierdo Laura , Medina Hector , Fogel Mark , Guerrero Carlos
Published: November 2024

Introduction:
Ebstein’s anomaly (EA) patients are at risk of arrhythmias. However, data regarding cardiac magnetic resonance (CMR) for predicting arrhythmic events using anatomic and functional parameters are scarce.

Goal/Aims:
To assess whether CMR-derived anatomical and functional data can predict arrhythmias in EA.

Methods:
Retrospective single-center cohort assessing EA patients referred for CMR between June 2016 and December 2023. Anatomic, volumetric and functional ventricular parameters were obtained from the CMR, and arrhythmias were found in the medical records. Arrhythmia occurrence was assessed from the CMR date (time-0), excluding pre-existing arrhythmias. Normality was assessed with Shapiro-Wilk for continuous variables, followed by a t-test or Wilcoxon. For categorical variables, we calculated chi-square or Fisher exact test. Receiver Operating Characteristic curves evaluated CMR predictors for arrhythmia occurrence. The 95% confidence interval lower bound must be > 0.5 to be statistically significant.

Results:
Forty-two patients were included (mean age 24.1 years±15.3); 21 (50.0%) were males. Other parameters are presented in Table1. There were 11 (26.2%) patients with arrhythmias after CMR: 72.7%patients developed supraventricular tachycardia, 18,2% atrial flutter, and 9.1% patients for each of the following: sustained ventricular tachycardia, atrial fibrillation and high-grade AV block. True tricuspid annulus (AUC=80.4, CI: 65.0-95.7) was a good predictor. In contrast, GOSE index (AUC=77.9, CI:63.3-92.5), apical displacement (AUC=76.4, CI:59.2-93.6), Ebstein’s angle (AUC=70.5, CI: 52.5-88.6), right atrial size (AUC=70.9, CI:54.6- 87.2) and right ventricular ejection fraction (AUC=74.2, CI:56.4-92.0) had fair predictive capacity (Figure1).

Conclusion:
CMR metrics predict arrhythmias in EA patients, with anatomic variables outperforming volumetric, but not functional ones. Larger studies are needed to confirm these findings.
Abstract 4140259: Bioresponsive Liposomal Nanoparticle-based Co-Delivery of tPA and DNase I Lyses tPA-Resistant Neutrophil Extracellular-Rich Clots
Authors: Raghunathan Shruti , Disharoon Dante , Hu Keren , Wang Hanyang , Hernandez Selvin , Sen Gupta Anirban
Published: November 2024

The nonsurgical standard of care for thrombosis is the administration of tPA. However, 40% of occlusive thrombi resist lysis by tPA. These resistant thrombi include both arterial and venous types, particularly those linked to ischemic stroke and deep vein thrombosis. Clot recalcitrance to tPA therapy is largely due to neutrophil extracellular traps (NETs), protein-rich extrusions of DNA that generate in blood clots following neutrophil recruitment and activation. However, the mechanism by which NETs contribute to tPA resistance remains unexplored.

To investigate NET-dependent tPA recalcitrance, we developed several microfluidic models for NET-rich blood clots. In these models, NET-rich blood clots were characterized by a core-shell structure, with NETs most tightly intercalated in the shell, and thicker fibrin colocalized with NETs. Correspondingly, only the shell exhibited significant resistance to tPA therapy in fibrinolysis assays. We observed that neutrophil elastase (NE), the primary enzymatic component of NETs, reduced the efficacy of tPA while DNase I increased its efficacy in the absence of NETs.

Therapeutic concentrations of tPA took 12.3±2.7 min to breach the tPA-resistant shell, which is significantly longer than the
in vivo
half life of tPA (5 minutes). DNase I, an enzyme that degrades NETs, restored tPA efficacy, allowing breach of the shell within 2.5 ± 1.2 min. Building on these findings, we hypothesized that localized co-delivery of tPA and DNase using nanoparticles could remediate clot recalcitrance while minimizing iatrogenic effects and protecting the drugs from degrading in circulation.

We engineered tPA-loaded nanoparticles (tPA-NPs) decorated with a fibrin-targeting peptide, and DNase-loaded nanoparticles (DNase-NPs) decorated with a NE-targeting peptide. A thrombin-cleavable substrate was incorporated into tPA-NPs such that they degraded upon exposure to thrombin, and an NE-cleavable substrate was incorporated into DNase-NPs such that they degraded upon exposure to NE. Upon triggered release, the nanoparticles achieved a concentration of 2 µg/mL tPA and NET-lytic activity equivalent to 50 IU/mL DNase I respectively.

In functional assays, the combination of DNase-NPs and tPA-NPs triggered complete clot dissolution within 12 min (n=4, p<0.05). In conclusion, the functionalized drug delivery system achieved localized co-delivery of tPA and DNase, resulting in complete lysis of clots that are recalcitrant to traditional therapies.