bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16755: Changes in Mid-Regional Pro-Adrenomedullin During Treatment With Sacubitril/Valsartan
Authors: Myhre Peder L , Liu Yuxi , Kulac Ian , Claggett Brian , Prescott Margaret , Felker Michael , Butler Javed , Pina Ileana L , Rouleau Jean L , Zile Michael R , McMurray John J , Ward Jonathan , Solomon Scott , Januzzi James L
Published: December 2023

Background:
Adrenomedullin is a vasodilatory peptide with a role in microcirculatory and endothelial homeostasis. Adrenomedullin is a substrate for neprilysin and may therefore play a role in beneficial effects of sacubitril/valsartan (Sac/Val) treatment.

Methods:
Mid-regional pro-peptide of adrenomedullin (MR-proADM) was measured in 156 patients with heart failure with reduced ejection fraction (HFrEF) treated with Sac/Val and 264 patients with HF with preserved EF (HFpEF) randomized to treatment with Sac/Val or valsartan. Echocardiography and Kansas City Cardiomyopathy Questionnaire results were collected at baseline and after 6 and 12 months in the HFrEF cohort.

Results:
Median (Q1-Q3) baseline MR-proADM concentrations were 0.80 (0.59-0.99) nMol/L in HFrEF and 0.88 (0.68-1.20) nMoL/L in HFpEF. After 12 weeks of treatment with Sac/Val, MR-proADM increased by median 49% in HFrEF and 60% in HFpEF, while there were no significant changes in valsartan-treated patients (median 2%). Greater increases in MR-proADM were associated with higher Sac/Val doses. Changes in MR-proADM correlated weakly with changes in N-terminal pro-B-type natriuretic peptide, cardiac troponin T and urinary cyclic guanosine monophosphate. Increases in MR-proADM were associated with decreases in blood pressure, but not significantly associated with changes in echocardiographic parameters or health status (
Figure
).

Conclusions:
MR-proADM concentrations rise substantially following treatment with Sac/Val, in contrast to no change from valsartan. Change in MR-proADM from neprilysin inhibition did not correlate with improvements in cardiac structure and function or health status. More data are needed regarding the role of adrenomedullin and its related peptides in the treatment of HF.
Abstract 16777: Do Not Clown Around With Intracardiac Myxomas: A Clinical Case of Carney Complex
Authors: Warren Amanda M , Zilberman Stephanie , DiStefano Natalie , pink kevin
Published: December 2023

Introduction:
Intracardiac myxomas are associated with cardiovascular mortality most frequently due to embolism and obstruction leading to heart failure. One of the most feared complications of intracardiac myxomas are sudden cardiac death, as these tumors are often identified incidentally. Carney Complex (CNC) is a rare disorder characterized by cardiac myxomas, psammomatous melanotic schwannomas, abnormal skin pigmentation, and endocrine disorders.

Clinical Case:
A 55 year old female with a past medical history of hypertension presented to the hospital with syncopal episodes and intermittent vision loss. Head computed tomography scan noted a large extra-axial mass present within the left cerebellopontine angle. A transthoracic echocardiogram showed a severely dilated left atria containing a large atrial mass (7.9 x 5.0 cm) that was causing obstruction of mitral inflow resulting in peak velocity 246 cm/S with a mean gradient of 12 mmHg. The patient was also noted to have dispersed epithelioid blue nevi present on skin examination. The patient met major criteria for diagnosis of Carney Complex.

Conclusion:
Carney complex (CNC) is an extremely rare autosomal dominant syndrome with less than 1,000 cases reported worldwide. Patients with familial history of intracardiac myxomas, multiple myxomas, characteristic skin findings, or endocrinopathies should be evaluated for CNC. Patients with cardiac myxoma secondary to CNC typically have a recurrence risk of roughly 30%. Patients with CNC should be screened with biannual transthoracic echocardiograms after resection and patients with suspected CNC should be worked up for additional tumor burden and endocrinopathies.
Abstract 16780: Single Cell Profiles of Human Heart Failure and Myocardial Diseases
Authors: Gidlof Olof , Czuba Tomasz , Pimpalwar Neha , Celik Selvi , Vukusic Kristina , Lundgren Jakob , Bollano Entela , Rentzsch Philipp , Martorella Molly , Linner Erik , Albinsson Sebastian , Boren Jan , Jeppsson Anders , Nilsson Johan , Natarajan Pradeep , Lappalainen Tuuli , Sandstedt Joakim , Levin Malin , Smith Gustav
Published: December 2023

Background:
Heart failure represents the end-stage of a range of diseases which adversely impact the heart muscle. The extent by which cellular and molecular mechanisms differ between myocardial diseases in heart failure remains incompletely understood.

Methods:
We performed isolation and droplet-based RNA-sequencing of 394 247 single nuclei from 103 explanted hearts from transplant and ventricular assist device recipients and 7 unused donor hearts without heart disease. After sample and nuclei level quality control, doublet removal and sample integration; principal component analysis and shared nearest neighbor clustering were used to identify distinct cell populations. Cell type composition and transcriptomic profiles were compared across donor hearts and 10 myocardial diseases (hypertrophic, dilated, ischemic, restrictive, arrythmogenic and non-compaction cardiomyopathy; rheumatic and congenital heart disease; cardiac amyloidosis and graft rejection; n=1-45/group).

Results:
We identified and manually annotated 14 distinct cell populations that were present across controls and myocardial diseases, including transcriptionally diverse subgroups of cardiomyocytes, endothelial cells and pericytes. Compared to controls, we observed disease-specific differences in cell populations with regards to composition, heterogeneity, and specific transcriptional profiles.

Conclusions:
Our results reveal differences in single cell profiles of individual heart muscle diseases compared to controls without heart disease.
Abstract 16789: Modeling the Optimal Strategy of Natriuretic Peptide Testing for Heart Failure Prevention in Diabetes: A Pooled Cohort Analysis
Authors: Patel Kershaw , Segar Matthew W , Klonoff David , Lam Carolyn S , Verma Subodh , Defilippis Andrew P , Nasir Khurram , Butler Javed , Vaduganathan Muthiah , Pandey Ambarish
Published: December 2023

Introduction:
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is associated with heart failure (HF) risk and measurement is recommended in diabetes. Incorporation of NT-proBNP with WATCH-DM, a HF risk score validated in diabetes, improved HF risk prediction in low-risk individuals (score <13). Whether WATCH-DM can improve the yield of NT-proBNP testing and inform allocation of SGLT2 inhibitors is unknown.

Methods:
Adults with diabetes and free of HF at baseline from ARIC, CHS, CRIC, DHS, FOS, and MESA cohorts were included. Participants without cardiovascular disease (CVD) were stratified into high- vs. low-risk categories based on 4 approaches: 1) WATCH-DM (score ≥ vs. <13); 2) NT-proBNP (≥ vs. <125 pg/mL); 3) WATCH-DM plus NT-proBNP (both high vs. not); 4) WATCH-DM-based NT-proBNP (if score <13, measure NT-proBNP) (either high vs. not). Five-year cumulative incidence rates of HF, number needed to treat (NNT
5
) and number needed to screen (NNS
5
) were estimated based on pooled treatment effects of SGLT2 inhibitors.

Results:
The study included 6,410 participants (47.5% women, 35.1% Black, 20.5% with CVD) with 428 (6.7%) incident HF events over 5-year follow-up. The 5-year risk of HF was 12.3% among participants with CVD and comparable to those without CVD identified as high-risk based on all 4 approaches (
Figure
). Among participants without CVD, WATCH-DM-based NT-proBNP identified 46% of participants as high-risk and accounted for 80% of HF events. The NNT
5
with an SGLT2 inhibitor to prevent 1 HF event in participants with CVD was 25 and similar to the primary prevention population identified as high-risk (
Figure
). The NNS
5
was lowest in the WATCH-DM-based NT-proBNP strategy (
Figure
).

Conclusions:
Selective NT-proBNP assessment based on a validated clinical risk score for HF improved the yield of testing and may represent an efficient approach to risk stratification and allocation of therapies among individuals with diabetes.
Abstract 16799: Galectin-1 Alleviates Aortic Valve Calcification via Modulating Integrin-Mediated Cytoskeletal Reorganization and Focal Adhesion
Authors: Lin Ying-wen , Hu Dongtu , Lin Xiangjie , Li Juncong , Su Shuwen , Xu Dingli , Zeng Qingchun
Published: December 2023

Background
Galectin-1, a beta-glycoside binding protein, has been reported to involve a variety of cell functions including proliferation, cell migration and focal adhesion. The role of cell-matrix interaction in calcific aortic valve disease (CAVD) is not fully investigated and whether galectin-1 is involved in this process remains unclear. We hypothesized that galectin-1 mitigates the fibrocalcific response and mechanosensitivity of valve interstitial cells (AVICs) by modulating integrin-mediated cytoskeletal reorganization and focal adhesion.

Methods and Results
We enrolled patients with CAVD and age- and sex-matched controls to detect serum galectin-1 and found that circulating galectin-1 was lower in CAVD. The expression of galectin-1 decreased in fibrocalcific valves and AVICs cultured in osteogenic medium (OM), as shown by western blot, qPCR, immunohistochemistry (IHC) and immunofluorescence. Silencing galectin-1 by short-interfering RNA exacerbated the fibrocalcific change of AVICs in vitro while recombinant galectin-1 (rGal-1) prevented these effects. AVICs cultured in OM also presented enhanced integrin signaling, cytoskeletal reorganization and focal adhesion. Anti-integrin blocking experiments and co-immunoprecipitation assays demonstrated that the galectin-1 directly interacted with integrin αvβ1 to regulate AVICs adhesion to a fibronectin matrix. Western blot, qPCR and Immunofluorescence assays confirmed that actin cytoskeletal reorganization was induced by αvβ1 activation through Rac1-WRC-Arp2/3 signaling axis. Western blot, alkaline phosphatase (ALP) as well as Alizarin red staining demonstrated that silencing galectin-1 enhanced AVICs sensitivity to piezo1 activation, which is dependent on αvβ1 binding and actin polymerization. In vivo, aortic valve disease was constructed by direct wire injury (DWI), and we showed that overexpression of galectin-1 by adeno-associated virus significantly decelerated the progression of aortic valve lesion induced by DWI in mice.

Conclusion
Galectin-1 interacts with integrin αvβ1 to modulate cytoskeletal reorganization and AVICs adhesion to fibronectin, thus mitigating the fibrocalcific response of AVICs and aortic valve calcification.
Abstract 16812: Value of Echocardiographic Variables to Predict Cardiotoxicity in Patients Using Machine Learning
Authors: MARTINS Helman C , Salemi Vera M , Melo Marcelo , Gaudencio Thais , Nobrega Yann , MEDEIROS EWERTON , Martins Ana Caroline P , Martins Helman Fernando P , Monteiro Elizabeth
Published: December 2023

Introduction:
Early identification of subclinical signs of cardiotoxicity in patients with breast cancer submitted to echocardiographic exam may change the natural history of patients undergoing treatment with anthracyclines.
Objectives:
The aim of this study was to identify echocardiographic and clinical variables related to cardiotoxicity and death analyzed using machine learning.

Methods:
The study consisted of a historical cohort of patients with breast cancer, submitted to chemotherapy treatment with anthracyclines, with clinical evaluation, electrocardiogram and echocardiogram performed before the first session,3 ,6 , 12 and 24 months later, with the intention to analyze echocardiographic markers to identify prognostic parameters related to cardiotoxicity.. Among various classifier models, the Extreme Gradient Booster (XGB) model was selected as the best instrument for predicting cardiotoxicity in this study. The SHAP (SHapley Additive exPlanations) approach was employed to assess the importance of each variable in the model.

Results:
The sample consisted of 58 patients, with a mean age of 50.29 (standard deviation = 13.32), who completed treatment between February 2010 and June 2011. The outcome measure was a composite of death or cardiotoxicity, with 11 patients in the positive group (mean age: 43.73, std: 13.08) and 47 in the negative group (mean age: 51.83, std: 13.05) The XGB model achieved an accuracy of 0.89, recall and precision of 0.67. The Area Under the Receiver Operating Characteristic Curve (ROC AUC) was 0.91 . Notably, echocardiographic variables such as Myocardial Performance Index (MPI), End Systolic Volume (ESV), End Diastolic Volume (EDV) and Systolic Blood Pressure (SBP) emerged as relevant predictors of the outcome figure 1.

Conclusions:
Echocardiographic indices may predict subclinical cardiotoxicity and which and may be confirmed in larger exploratory studies.
Abstract 16816: The Impact of Age in Patients Undergoing Impella-Assisted High-Risk Percutaneous Coronary Intervention: It Gets Complicated
Authors: Bimal Tia , Ukrani Janta , Fishbein Joanna , Selim Samy , Gandotra Puneet , Ong Lawrence , Gruberg Luis
Published: December 2023

Background:
The Impella ventricular assist device is often used in patients (pts) with complex coronary artery disease undergoing high-risk percutaneous coronary interventions (PCI). Limited data exits on the risks and benefits of these devices in elderly pts.

Aim:
To compare major bleeding and major adverse cardiac and cerebrovascular events (MACCE) in pts undergoing Impella-assisted PCI, categorized by age groups.

Methods:
Data was collected for quality control on pts undergoing Impella-assisted PCI. Pts were divided by age into three groups: ≤69, 70-79 and ≥80 years. Bleeding was classified by Bleeding Academic Research Consortium (BARC). MACCE was the composite of major bleeding (BARC ≥3), death and post-PCI myocardial infarction and stroke.

Results:
From 2010 to 2018, 252 pts had Impella-assisted PCI (Table). Pts ≤69 were often male, presented with STEMI or NSTEMI (61%) and had lower left ventricular ejection fraction (LVEF) complicated by cardiogenic shock (CS). Bleeding complications, mortality and MACCE were similar among the groups. Covariate adjustment showed pts 70-79 were not at a higher risk of MACCE compared to ≤69 pts, whereas pts ≥80 had 2.7-fold odds of MACCE compared to pts ≤69 (Figure).

Conclusion:
In Impella-assisted PCI pts: 1) indications for Impella varies across different ages; 2) younger pts (≤69) were healthier but in the midst of an acute coronary syndrome with severely reduced LVEF and CS; 3) BARC ≥3, mortality and MACCE were similar among the three groups; 4) by multivariable analysis, older age, female sex, STEMI and pre-PCI CS were independent predictors of MACCE; and 5) the odds of MACCE increased by almost 3-fold in pts ≥80 when compared to younger pts.
Abstract 16843: Diastolic Dysfunction Due to Structual Changes in Mutant Troponin I May Cause Restrictive Cardiomyopathy; Cryo-Electron Microscopic Analysis Using Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Hasegawa Moyu , Kawamura Takuji , Harada Akima , Ito Emiko , Takeda Maki , Taira Masaki , Watanabe Takuji , Kugo Yosuke , Yoshioka Daisuke , Shimamura Kazuo , Miyagawa Shigeru
Published: December 2023

Introduction:
Restrictive cardiomyopathy (RCM) is characterized by ventricular diastolic dysfunction with preserved contraction. Since there is no effective treatment other than heart transplantation, the development of novel treatment strategy by elucidating pathophysiology of RCM is an important issue under the serious donor shortage.Various troponin I mutations have been reported in patients with RCM and given that troponin I regulates the inhibition of cardiac contraction, it is possible that structural changes in mutant troponin I cause diastolic dysfunction in RCM. Recently, cryo-electron microscopy (cryo-EM) has made it possible to analyze the structure of thin filaments of muscle fibers. In this study, we applied the technology of induced pluripotent stem cell (iPSC) to cryo-EM structural analysis of thin filaments in cardiomyocytes from RCM patients with troponin I mutations.

Methods:
We established an iPSC line from a pediatric RCM patient with heterozygous TNNI3 mutation (R170W). Then the iPSCs were differentiated to cardiomyocytes to compare the cellular physiological, structural features. Normal adult iPS cell derived cardiomyocytes (Ctrl-iPSC-CM) were used as control. We also extracted thin filaments from iPSC-CMs and analyzed their structure with cryo-EM.

Results:
PCR analysis revealed the percentage of mutant alleles in
TNNI3
mRNA was about 80% in the differentiated RCM-iPSC-CM, which was similar to the results in the myocardium of the same patient. The RCM-iPSC-CM demonstrated slower diastolic rate and longer diastolic time by cell motion analyses than Ctrl-iPSC-CM. Immunostaining showed a disarrayed sarcomeres in the RCM-iPSC-CM. Tthe structure of the thin filaments extracted from the RCM-iPSC-CMs observed with cryo-EM was close to that in the presence of calcium (contractile myocardium), even though the filaments were purified in the absence of calcium.

Conclusions:
The iPSC-derived cardiomyocytes could effectively represent the diastolic dysfunction of RCM. The structures of thin filaments were possibly explained for the phenotype of restrictive cardiomyopathy.
Abstract 16846: Three-Dimensional Assessment of Ascending Aortic Motion by Dynamic CT in Sporadic and Marfan Thoracic Aortic Aneurysm
Authors: Tjahjadi Nic , Kim Taeouk , Marway Prabhvir S , Campello Jorge Carlos Alberto , Knauer Heather , van Herwaarden Joost , Hazenberg Constantijn , Patel Himanshu J , Figueroa C A , Burris Nicholas S
Published: December 2023

Background:
The ascending aorta exhibits a complex, 3D motion related to cyclic pressure changes and downward traction forces related to left ventricular contraction. However, most metrics of disease severity are static (i.e., diameter) and among prior studies that have investigated ascending aortic motion, 2D imaging is typically employed. Vascular deformation mapping (VDM) is an image analysis technique that accurately quantifies 3D displacement of the aortic wall.
Aims
We aimed to quantify 3D metrics of cyclic ascending aortic motion and distensibility in patients with aTAA, and evaluate associations between motion metrics and patient characteristics in sporadic TAA (SaTAA) and Marfan syndrome (MFS).

Methods:
We included adult patients with aTAA, either SaTAA or MFS, and multi-phasic CTA of the thoracic aorta. VDM analysis of CTA data was performed with metrics including: 1) Axial, in-plane and rotational displacements at the root, 2) distensibility assessed by cyclic 2D cross-sectional area change (Dist-2D) at the root [(ΔA/A diastole х PP)], and 3) distensibility assessed by VDM-derived cyclic surface area stretch [(Area ratio-1)*1/PP] at the root and tubular ascending (Dist-3D). Aortic growth rate (GR) was measured from follow-up CTA.

Results:
We analyzed 51 with SaTAA (33% female, 62 ± 11 years old), and 14 with MFS (50% female, 42 ± 13 years old). In SaTAA, Dist-2D was associated (β=0.59, p=0.047) with axial displacement and AI was strongly associated (β=1.03 p=0.001) with rotation. In MFS, BAV and diameter were associated with in-plane displacement (β=5.50, p=0.004; β=-0.026, p=0.001). Among MFS patients with follow-up CTAs (n=10), ascending distensibility (Dist-3D) was marginally negatively associated with ascending GR (β= -0.27, p=0.058)

Conclusion:
3D analysis of aortic motion in aTAA showed differences in root motion, namely related to valve disease and age, as well as differences in aortic distensibility that may predict ascending aortic GR in MFS.
Abstract 16854: Successful Retention of Vulnerable Populations in New York City: The BETTER-BP Randomized Trial
Authors: Clarke Erika , Gutierrez Yasmin , de Brito Stefany , Meng Yuchen , Adhikari Samrachana , Dodson John A , Schoenthaler Antoinette
Published: December 2023

Introduction:
Clinical trial retention in safety-net practices is challenging. To better understand reasons for loss to follow-up, we analyzed data from an ongoing clinical trial in the NYC public hospital system.

Methods:
We analyzed the first 185 participants enrolled in the BETTER-BP study, an ongoing randomized trial of wireless antihypertensive medication adherence monitoring with a financial incentive lottery to promote medication taking behavior. BETTER-BP enrolls participants from two NYC public hospitals (Bellevue and Gouverneur) and follow-up lasts 12 months. We reported the rate of loss to follow-up at 12 months and assessed baseline characteristics (age, sex, race, ethnicity, insurance status, BMI, blood pressure, comorbidities, and substance use) of those lost vs. retained. ANOVA was used for continuous variables, and the Chi-squared test for categorical variables.

Results:
Median age was 55.0 (47.5, 62.5) years, 59% were female, 59% Hispanic, and 26% Non-Hispanic Black. Three quarters were Medicaid-insured or uninsured. There were 155 participants retained at 12 months (83.8% retention rate). Characteristics of those retained vs. lost to follow-up are shown in the Table. Participants who were lost to follow-up were more likely to report current alcohol use (43.3% vs. 36.8%, p < 0.001) and illicit substance use (16.7% vs. 3.9%, p < 0.001). Notably, missingness in alcohol use and illicit substance use was also higher among those lost to follow up. Other baseline characteristics were similar between the two groups.

Conclusion:
Overall retention was high (>80%). Alcohol and illicit drug use were associated with loss to follow up and may serve as markers for future strategies to mitigate attrition.
Abstract 16869: Prevalence of Valvular Heart Disease in the Elderly as Observed in a Large-Scale Echocardiographic Database
Authors: Hieda Michinari , Rikumaru Kayo , Yamamoto Yuko , Futami Shutaro , Yamashita Kazumi , Maruyama Toru , Hara Hiroshi
Published: December 2023

Introduction:
In Japan, the aging population is increasing, leading to a rapid rise in elderly patients with heart failure. To determine the post-test probability of valvular heart diseases, it is crucial to understand the pre-test probability and likelihood ratio.

Hypothesis:
Therefore, we surveyed the prevalence of valvular diseases among elderly individuals in a large-scale echocardiographic database of echocardiology.

Methods:
We reviewed 4,023 patients (1,486 males and 2,537 females, 79.4±14.3 years) who underwent echocardiographic examinations at our hospital from October 2017 to September 2022. The prevalence of valvular heart diseases was calculated by dividing the number of patients with valvular diseases by the total number of patients surveyed. We analyzed the data by age, gender, and severity of valvular disease to determine the prevalence in each subgroup.

Results:
Among the 4,023 individuals included in the study, 2,652 elderly patients (65.9%) had valvular diseases: 808 cases of aortic stenosis (AS) (20.1%), 1,356 cases of aortic regurgitation (AR) (33.7%), 1,899 cases of mitral regurgitation (MR) (47.2%), and 52 cases of mitral stenosis (MS) (1.3%). A total of 981 individuals (24.4%) had moderate or severe valvular disease, including 225 patients of AS (5.6%), 178 patients of AR (4.4%), 560 patients of MR (13.9%), and 18 patients of MS (0.5%). In gender-specific analysis, women had a higher prevalence of valvular heart disease than men, with approximately 1.3 to 2.5 times higher incidence in average males.

Conclusions:
We investigated the prevalence of valvular heart disease in the elderly using a large-scale echocardiographic database and found that over 65% of elderly individuals had valvular heart disease. In particular, AS and MR had relatively high prevalence rates for moderate or severe valvular disease, highlighting the importance of screening through routine physical examinations and echocardiographic tests.
Abstract 16897: The Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Among Individuals With and Without Baseline Atherosclerotic Cardiovascular Disease: The Mass General Brigham Lp(a) Registry
Authors: Berman Adam N , Biery David , Besser Stephanie , Singh Avinainder , Weber Brittany N , Huck Daniel M , Divakaran Sanjay , Hainer Jon , Shiyovich Arthur , Kaur Gurleen , Blaha Michael J , Cannon Christopher P , Plutzky Jorge , Januzzi James L , Booth John N , Lopez J. A , Kent Shia , Nasir Khurram , Di Carli Marcelo , Bhatt Deepak L , Blankstein Ron
Published: December 2023

Introduction:
Lipoprotein(a) [Lp(a)] is associated with increased atherosclerotic cardiovascular disease (ASCVD) events. However, whether the optimal Lp(a) threshold for risk-assessment should differ based on baseline ASCVD status is unknown.

Hypothesis:
To assess the association between Lp(a) and major adverse cardiovascular events (MACE) among patients with and without a history of ASCVD.

Methods:
Retrospective cohort of patients with Lp(a) measured at two academic medical centers in Boston, MA from 2000-2019. To assess the association of Lp(a) with incident MACE (cardiovascular mortality, myocardial infarction, or ischemic stroke), the following Lp(a) percentile groups were generated: 1
st
-50
th
(0 - 41 nmol/L; reference), 51
st
-70
th
(42 - 111 nmol/L), 71
st
-90
th
(112 - 215 nmol/L), 91
st
-100
th
(>216 nmol/L). Individuals with severe renal dysfunction or a malignant neoplasm were excluded. Cox proportional hazards modeling was used to assess the association of Lp(a) percentile group with MACE.

Results:
After applying eligibility criteria, 16,419 patients (median age 60, 41% female) were analyzed with a median follow up of 11.9 years. Patients with ASCVD were older and had higher rates of cardiovascular risk factors. Among the 10,181 (62%) patients with a history of ASCVD, individuals in the 71
st
-90
th
and 91
st
-100
th
percentile groups had similarly increased hazards of MACE (adjusted HR = 1.33, p<0.001 and adjusted HR = 1.34, p<0.001 respectively). Among the 6,238 individuals without baseline ASCVD, only individuals in the 91
st
-100
th
Lp(a) percentile group had a significantly increase hazard of MACE (adjusted HR 2.05, p<0.001),
Figure
.

Conclusions:
In a large, contemporary US cohort, elevated Lp(a) is independently associated with long-term MACE among individuals with and without baseline ASCVD. Our results suggest that the Lp(a) threshold for risk assessment may be lower in secondary prevention when compared with primary prevention.
Abstract 16963: A Nation-Wide Study on Incidence, Mortality and Case Fatality of Acute Coronary Syndrome Reveals Levelling Off of the Incidence Decrease Among Young Women Aged 35-54 Years in 1996-2021 in Finland
Authors: Kallstroem Atte , Holopainen Ida , Kambur Oleg , Perola Markus , Salomaa Veikko V , Havulinna Aki S , Räsänen Markus , Sinisalo Juha
Published: December 2023

Introduction/background:
Incidence and case fatality (CF) of acute coronary syndrome (ACS) have declined in the last decades, but cardiovascular disease remains one of the leading causes of death in the Western world. The knowledge of the current trends in incidence, mortality, and CF of ACS from Finland and even worldwide is sparse, though some studies have suggested slowed incidence decrease and even increase in younger age groups. Thus, we set out to investigate the changes in these event rates in Finland from 1996 to 2021.

Research questions/hypothesis:
To examine how the ACS burden has evolved in Finland from 1996 to 2021, especially after 2010.

Methods/approach:
We used Finnish country-wide registers, i.e., Hospital Discharges Register (HDR, from Care register for health care) and the National Causes of Death Register with complete coverage of non-fatal and fatal ACS events. We analyzed incidence and mortality rates, and CF, as well as the significance of their trends using negative binomial and logistic regression adjusting for age and sex.

Results/data:
Altogether, 186 489 non-fatal and 72 907 fatal incidents of ACS events were included in the analysis. ACS incidence decreased in men (Annual percentage change (APC) -2.0% [95% CI -2.2 to -1.8]) and in the older age groups of women (APC of 55-64-year-old -1.5% [-1.7 to -1.2] and

65-74-year-old -3.3% [-3.5 to -3.1]), but the decrease in incidence slowed down over the last decade. Importantly, in 35-54-year-old women ACS incidence decrease halted (APC of 35-44-year-old 0.4% [-0.3 to 1.0] and 45-54-year-old 0.2% [-0.1 to 0.5]). ACS mortality and case-fatality declined steadily in both sexes and all age groups throughout the study period (APC of the mortality in men -4.5% [-4.7 to -4.3] and in women -5.1% [-5.3 to -4.7]. APC of the CF in men -2.7% [-2.9 to -2.6] and in women -3.4% [-3.6 to -3.2]).

Conclusions:
In concordance with other recent reports, we showed that the ACS mortality in both men and women was steadily decreasing. However, we observed that ACS incidence decline slowed down in older age groups and even halted in women aged 35-54. These alerting results emphasize the need for cardiovascular prevention, particularly in young and middle-aged women.
Abstract 16973: Using an in-vitro and ex-vivo Test Platform for Evaluation of a Pen-Sized Ultrasound Vascular Access Device (Vu-Path)
Authors: Hernandez-Torres Sofia I , Snider Eric J , Berard David M , Rothstein Robert , Abraham Theodore
Published: December 2023

Introduction:
Despite several off-the-shelf ultrasound systems being used for large vessel access, reliable and safe vascular access remains a problem. This is especially true during combat casualty care where skilled operators may not be available. We tested a novel small-footprint platform for efficacy and timeliness of large vessel access at normovolemic and hypovolemic states

Hypothesis:
A custom-designed device with optimized ergonomics and workflow will yield high success rates and low training needs for large vessel access

Methods:
Vu-Path has a pen-size 10 mm ultrasound transducer with a proprietary needle guide and a lightweight engine deployed with a tablet or laptop. The display has an overlay showing the needle insertion path. Once the vessel is visible within the overlay, insertion of the needle using the needle guide directs insertion to the vessel. We used 3 models to simulate femoral vessel access: 1) a commercially available phantom (CAE Blue Phantom); 2) a custom in-vitro tissue phantom mimicking swine normovolemic and hypovolemic femoral vascular states; 3) an ex-vivo model of a euthanized swine lower-body section with canulated femoral vessels looped with a peristaltic pump to simulate normovolemic and hypovolemic states.

Results:
Vu-Path tested in these 3 models resulted in 87% successful insertions across all models and conditions; 100% success on the commercial model versus 83% in the custom tissue phantoms. In every model, 2 metrics were evaluated as summarized in Figure: total time to align vessel in the needle track window, and total time after aligning to confirmed insertion. Mean attempts needed to gain system expertise was 6.

Conclusions:
Vu-Path had high success rates for vessel visualization and needle access guidance in 3 models simulating normovolemic and hypovolemic conditions. Training requirements were minimal. These data suggest Vu-Path is capable of potentially improving safety and reliability of large vessel access.
Abstract 16977: Determining Rates of Meaningful 30-day Health Status Changes Following Transfemoral Carotid Artery Stenting
Authors: Kluger Jonathan , Romain Gaelle , Cleman Jacob , Scierka Lindsey , Grubman Scott , Pajarillo Carmen S , Schenck Christopher , Smolderen Kim G , Mena-Hurtado Carlos
Published: December 2023

Introduction:
While carotid artery revascularization studies have focused on clinical endpoints such as death, MI, and stroke, few cover these treatments’ effect on health status. We previously established minimal clinically important differences (MCIDs) to assess clinical improvement or worsening in generic health status for patients undergoing transfemoral carotid artery stenting (TF-CAS) and aimed to use these to study the distribution of health status responders following TF-CAS.

Methods:
We studied patients in the multicenter Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) registry who underwent TF-CAS between 2010 and 2014 and completed either the EQ-5D-3L or SF-36 (two generic health-related quality-of-life surveys) within the first 28 days before TF-CAS and 30 days after. Patients were classified as improving, worsening, or experiencing no change based on score changes relative to distribution-based MCIDs of 0.09 and 11.00 for the EQ-5D-3L index value and visual analog scale (VAS) subscales, respectively, and 4.70 and 5.40 for the SF-36 mental and physical component summaries (MCS and PCS), respectively. We then stratified both cohorts by symptom status, defining symptomatic patients as having symptoms suggesting prior stroke or TIA.

Results:
This study included 3,930 patients (27.74% symptomatic) who completed the EQ-5D-3L and 3,018 (30.45% symptomatic) who completed the SF-36. For the full cohorts across the four subscales, 21.17%-26.11% improved, 10.53-16.67% worsened, and 57.22-66.06% experienced no change. The distributions of changes in scores by symptom status overlapped significantly (Figure 1).

Conclusions:
Roughly 20-25% of patients, regardless of symptom status, improved in terms of generic health status following TF-CAS, while about 70-80% worsened or experienced no change. Disease-specific instruments would further elucidate the effect of TF-CAS on patients' health status.
Abstract 16979: Posterior Wall Ablation With Cryoballoon in Persistent Atrial Fibrillation
Authors: Bloemhard Miaoli , Berkland Victor , Bernstein Hannah , Robinson Carly , Iyer Rahul , Fan Dali , Munir Bilal , Srivatsa Uma N
Published: December 2023

Background:
Posterior wall ablation (PWA) in addition to pulmonary vein isolation (PVI) has been suggested to improve outcomes in persistent atrial fibrillation (PeAF). Endocardial radiofrequency ablation is frequently inadequate to achieve electrical silence of PW.

Aim:
To contribute to the real-world data of the efficacy of PWA with cryoballoon in treating PeAF.

Methods:
This is a single-center, retrospective study including patients with PeAF referred for catheter ablation between 2015-2019 who underwent either PVI or PVI+PWA. PeAF was defined in accordance with current guidelines. PWA was achieved by cryoballoon; repeat map was used to confirm electrical silence (<0.05mV). Time to ablation (TTA) was defined as the time between first documented AF diagnosis and ablation. Patients were monitored for recurrence of AF or other atrial arrhythmia, defined as atrial tachycardia or flutter, through 1-year follow-up.

Results:
A total of 119 patients were included, 43 (36.13%) underwent PVI alone and 76 (63.87%) underwent PVI+PWA. PVI and PWA groups had similar baseline characteristics (Table 1). All patients in PWA cohort had complete electrical silence in PW. One-year follow-up occurred at a mean of 370.46
+
91.70 days after ablation. PWA was associated with decreased AF recurrence at 1-year follow up (35.90% in PVI vs 16.44% in PWA, OR 0.35, 95%CI 0.14-0.86, p = 0.023). In multivariate logistic regression, when controlling for age, longstanding persistent AF and TTA the association of PWA with decreased AF recurrence became stronger (OR 0.27, 95%CI 0.10-0.73, p = 0.010). PWA was not associated with a significantly increased rate of other atrial arrhythmia at 1-year follow-up (23.08% in PVI vs 13.70% in PWA, OR 0.53, 95%CI 0.19-1.44, p = 0.212).

Conclusion:
In comparison to PVI alone, PWA leads to decreased AF recurrence without increase in other arrhythmia at one year follow-up in PeAF. Cryoballoon technique may offer a more complete ablation in PW contributing to efficacy.
Abstract 16981: A Machine Learning Model Increases Genetic Confirmation of UKB Participants With Suspected Monogenic Cardiovascular Disease
Authors: Ramaker Megan E , Abdulrahim Jawan W , Corey Kristin , Coles Sara , Nafissi Navid A , Amos Kaitlyn , Kwee Lydia C , Shah Svati H
Published: December 2023

Introduction:
Monogenic cardiovascular diseases (MCVDs) are collectively common yet highly underdiagnosed. Genetic testing for pathogenic variants can facilitate diagnosis and familial screening of MCVDs. Yet, most genetic variants within MCVD-associated genes currently annotated in ClinVar are variants of uncertain significance (VUS). VUS clinical utility is limited as VUS cannot be used for genetic confirmation of disease or for familial cascade screening. We previously developed a disease- and tissue-specific machine learning model for reclassification of VUS (Cardiovascular Disease-Pathogenicity Predictor [CVD-PP]). We sought to determine if use of CVD-PP on VUS identified through whole exome sequencing (WES) would increase genetic diagnosis of patients suspected of having a MCVD in the UK Biobank (UKB) cohort.

Methods:
We filtered for variants in 47 genes associated with 5 MCVDs (cardiomyopathies, channelopathies, aortopathies, cardiac amyloidosis, and familial hypercholesterolemia) in UKB participants with WES data. Participants harboring an American College of Medical Genetics confirmed ClinVar pathogenic or likely pathogenic (P/LP) variant in one of these genes were excluded. Phenotyping for presence of MCVDs was performed using EHR, clinical, cardiac imaging, and ECG data. CVD-PP was utilized to predict the pathogenicity of variants that were classified as VUS, had conflicting interpretations, or were absent from ClinVar.

Results:
Of participants with QC’ed WES data in UKB (n=452,933), 34.7% (n=157,030) had expression of a MCVD. Of these, 0.51% (n=799) carried a P/LP variant in a MCVD gene. Of the remaining P/LP variant-negative participants expressing disease (n=156,231), 4.1% (n=6,346) carried a VUS or non-ClinVar variant that was predicted pathogenic by CVD-PP.

Conclusion:
We demonstrate the potential utility of using a disease-and tissue-specific computational tool, CVD-PP, for deeper characterization of VUS in MCVD genes. Prioritization of CVD-PP-predicted pathogenic variants increases yield of genetic diagnosis in patients with evidence of clinical MCVDs from 0.51% using only ClinVar P/LP variants to 4.6% in UKB. This work provides a potential framework for increasing overall diagnostic yield of MCVDs.
Abstract 16998: A Novel Preclinical Model of Calcified Coronary Chronic Total Occlusion
Authors: Gruslova Aleksandra B , Nolen Drew , Diaz Sanmartin Luis A , Aslam Mohammed I , Vela Deborah , Buja Louis M , Valen Andrew , Valen Maurice , Elliott James J , Feldman Marc D
Published: December 2023

Introduction:
These is significant research into the development of new medications and devices to treat chronic total occlusions (CTO). However, there is a lack of large animal models which reproduce the anatomy of clinical CTOs.
Aim:
Create an experimental model that mimics the anatomic features of human CTOs.

Methods:
CTOs were created in coronary arteries of live Yorkshire pigs (weight 80-120 lbs). The bioactive dental plug material (OsteoGen® Plug, Impladent Ltd) was implanted into the middle segment of one of coronary arteries (LAD, LCX or RCA). Angiography (C- Arm, Siemens) was performed before, immediately after plug implantation and before autopsy to confirm the presence of a CTO lesion. Animals were sacrificed at 9 hours to 3 months (n=12) and all coronary arteries underwent histopathological examination.

Results:
Histopathologic assessment confirmed that the bioactive plug composed of calcium apatite crystals and bovine collagen matrix mimics the pathological appearances of human CTOs. Serial histological sections showed complete resorption of the collagen matrix with replacement by fibrotic tissue 2 months after plug implantation, while the calcium content remains in the CTO.

Conclusions:
We have developed a reproducible model of calcified CTOs in pigs. Our model can provide a platform for evaluation of new drugs and devices for the treatment of calcified CTOs as well as to serve as a live model for training interventional cardiologists learning to cross CTOs.
Abstract 17011: Correlation of Surface Atrial ECG Dominant Frequency to Intracardiac Atrial Electrogram Dominant Frequency
Authors: Zaatari Ghaith , Bohorquez Jorge , McDermott Laura , Mitrani Raul , Blandon Catherine , velasquez alex , Lambrakos Litsa , Goldberger Jeffrey J
Published: December 2023

Background:
The surface Atrial ECG (A-ECG) is an underused tool in persistent atrial fibrillation (PeAF) that can provide dominant frequency (DF) of atrial activation. The association between A-ECG DF and left (LA) and right atrial (RA) DF has not been established.

Research Question:
Does surface A-ECG DF correlate with intracardiac DF?

Aims:
To investigate the correlation between A-ECG peak DF and peak DF of intracardiac RA and LA electrograms (EGM) in patients with PeAF.

Methods:
Thirty-two patients (age 63±9 years; 71% males) with PeAF underwent 5-minute epochs of surface ECG and comprehensive LA (261.5±185.1 sites/patient) and RA (211.5±174.6 sites/patient) intracardiac mapping with 15 second recordings. The A-ECG was derived by QRST subtraction and independent component analysis filtering, and divided into overlapping10-second windows which were subjected to Fast Fourier Transform (FFT). 4 were excluded for significant artifact. A-ECG DF was calculated for each lead from the power spectrum as the average of all 10-second segments. Peak A-ECG DF was determined by regional lead location and for all 12 leads. The intracardiac EGM DF was calculated from the FFT, and peak RA and LA DF was determined.

Results:
A-ECG peak DF was significantly lower than intracardiac peak DF 6.08±0.64 vs 9.72±1.19 Hz, p<0.0001(LA: 9.72±1.20 Hz, p<0.0001; RA: 8.40±0.80 Hz, p<0.0001). Figure shows that A-ECG peak DF correlated with peak RA DF, r=0.77 (p<0.0001), but not with peak LA DF (r=0.31, p=0.10). Regional A-ECG lead group DF correlated with RA DF (Inferior (II, III, aVF): r=0.79, p<0.0001; Lateral (I, aVL, V5-6): r=0.78, p<0.0001; Anterior (V1-3): r=0.75, p<0.0001) but not with peak LA DF.

Conclusion:
Surface A-ECG DF correlates with intracardiac RA DF and not LA DF. As in atrial flutter, the RA plays a prominent role in the surface ECG manifestation of the f waves. Further study is needed to determine whether A-ECG DF can be used to identify RA versus LA drivers that may require ablation.
Abstract 17022: Transcriptomic Analysis of Calciphylaxis Tissue Reveals Novel Genes Related to Vascular Calcification and Overlap With Coronary Artery Disease
Authors: Lee Sujin , Roh Kangsan , Singh Kuldeep , Jiang Wanlin , Ostrom Katrina , Birchenough Claire , Kajuluri Lova , Johnson Adam L , Krinsky Scott , Bouchouari Houda , Lino Cardenas Christian L , Eagleton Matthew , Nazarian Rosalynn M , Miller Clint L , Nigwekar Sagar , Malhotra Rajeev
Published: December 2023

Introduction:
Calciphylaxis is a rare, understudied disease of accelerated vascular calcification affecting the skin and soft tissue leading to painful wounds, amputations, and reduced survival. The underlying mechanisms of calciphylaxis remain incompletely understood.

Objective:
In this study, we aimed to identify altered signaling pathways and novel differentially expressed genes (DEGs) associated with calciphylaxis and to characterize the protein expression of top DEGs in the vasculature.

Methods:
6 case and 3 control tissues were obtained from our institution’s calciphylaxis biorepository (NCT03032835). RNA sequencing analysis and pathway analysis were performed using the KEGG database. Immunofluorescent (IF) staining with co-localization analysis was performed on independent case-control samples for the top 9 upregulated DEGs.
In vitro
functional assessment was performed using human vascular smooth muscle cells (VSMC).

Results:
783 DEGs (FDR-adjusted p-value ≤0.05) were identified, 543 of which were upregulated (Fig 1A). 27 altered pathways enriched for calcification, thrombosis, and inflammation were identified. The top 9 upregulated DEGs (adjusted p-values ≤1.2 x10-7) were KYNU, IFI16, KCNJ15, RAB31, FNDC1, HIF1α, DEPP1, NFIL3, and TSP1. On IF, 7 of the top 9 upregulated DEGs exhibited higher protein expression compared to matched controls, some of which are highlighted in Figure 1B. These 7 genes were all upregulated in RNA sequencing analysis of human coronary arteries with atherosclerotic lesions compared to coronaries without lesions. Functional assessment of the top 3 genes in this coronary artery disease analysis (FNDC1, KYNU & KCNJ15) revealed potent effects on calcification, proliferation, and migration of VSMCs.

Conclusions:
Novel genes identified in this transcriptomic study of calciphylaxis uncovered similarities with coronary artery disease and have identified previously unknown regulators of VSMC calcification.
Abstract 17038: Mineralocorticoid Antagonist Use for Transthyretin Amyloid Cardiomyopathy and Associated Outcomes
Authors: Stern Lily K , Kim Seong Kyu , Singer-Englar Tahli , Kobashigawa Jon A , Kittleson Michelle M , Patel Jignesh K
Published: December 2023

Background:
Diuretics have been the mainstay of symptomatic treatment for patients with amyloid cardiomyopathy however, there remains no established guideline directed medical therapy for this population. The anti-fibrotic properties of mineralocorticoid antagonists (MRA) are intriguing for potential use in transthyretin amyloid cardiomyopathy (ATTR CM); while they have shown promise for treatment of patients with heart failure with preserved ejection fraction, their use has never been studied specifically in the ATTR CM population. The purpose of our study is to evaluate the real-world use of MRA and associated outcomes in patients with ATTR CM at a large cardiac amyloid treatment center.

Methods:
Between 2009 and 2023, 168 patients with ATTR CM at our center were assessed for history of MRA use. Biomarkers, including baseline levels of troponin and natriuretic peptides, as well as kidney function were assessed. We also assessed the outcomes of 5-year survival, need for heart transplant, hospitalization, and mechanical circulatory support (MCS) use.

Results:
Of the 168 patients, 49 (29%) had a history of MRA use and 119 (71%) had no prior use. Between the two groups, there was no significant difference in age, frequency of ATTR CM subtype, kidney disease, or biomarker level at the time of diagnosis. While 5-year survival and need for MCS were similar between the two groups, there was a higher rate of transplant and hospitalization in the MRA use group.

Conclusion:
In a cohort of patients with ATTR CM, MRA use is uncommon and was not associated with improved outcomes. It was associated with higher rates of hospitalizations and heart transplantation; however, this may represent confounding by indication. Future investigations with larger registry cohorts and randomized control trials are warranted for further evaluation of biological and clinical effect of MRA use.