bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13463: Effect of an Intervention to Reduce Sedentary Behavior on Blood Pressure in Desk Workers: The RESET BP Randomized Clinical Trial (RCT)
Authors: Barone Gibbs Bethany , Perera Subashan , Huber Kimberly , Paley Joshua , Conroy Margaret B , Jakicic John , Muldoon Matthew F
Published: December 2023

Introduction:
High sedentary behavior (SB) is associated with cardiovascular (CV) risk in cohort studies, yet definitive data from RCTs of SB reduction on CV risk factors is lacking.

Hypothesis:
A 3-month SB reduction intervention would decrease blood pressure (BP) and pulse wave velocity (PWV) in sedentary adults.

Methods:
We recruited desk workers with systolic BP (SBP) 120-159 mmHg or diastolic BP (DBP) 80-99 mmHg, not on antihypertensives, and reporting low physical activity. Participants were randomized 1:1 to a 3-month SB reduction intervention or control. The intervention targeted replacing sitting with standing and stepping via health coaching, a wrist-worn activity prompter, and a height-adjustable workstation. All day and work-specific SB, standing, stepping, and steps were measured by a thigh-worn triaxial accelerometer. Protocolized office SBP (primary outcome), DBP, and HR were measured in duplicate on two occasions at each baseline and 3 months; 24-hr ambulatory BP and carotid-femoral PWV via tonometry were also measured. Changes in outcomes were compared across groups using analysis of covariance and mixed models.

Results:
Participants (n=271) had mean age 45 y and BP 129/83 mmHg; 60% were female and 82% were non-Hispanic White. Retention was 97%. Intervention participants reduced SB during work (-1.3 hr/day) and across all waking hours (-1.1 hr/day) compared to controls (both p<0.001). Intervention participants increased work-specific standing (1.2 hr/day), stepping (5 min/day) and steps (398/day) and all day standing (1.0 hr/day), stepping (7 min/day) and steps (528/day) compared to control (all p<0.05). Yet, the intervention did not yield a greater reduction in BP or PWV vs. controls (all p>0.05). Differences in changes were office SBP -0.24 mmHg (p=0.793), DBP 0.08 mmHg (p=0.894), and heart rate -2.75 (p=0.190). Findings were similar for 24-hr, daytime, and nighttime ambulatory BP averages (all <1.2 mmHg; p>0.05). Differences in PWV were higher (opposite from the hypothesized direction) in intervention vs. control and approached significance (0.18 m/s, p=0.07).

Conclusions:
In sedentary desk workers with mild-moderate untreated BP, this 3-month intervention reduced daily SB by about one hour but did not improve BP or PWV.
Abstract 13465: Tirzepatide vs. Semaglutide for Secondary Prevention of Major Adverse Cardiovascular Events in Patients With Type 2 Diabetes Mellitus With an Initial HbA1c of >8.5 - A Value for Money Analysis
Authors: Azuri Joseph , Aboalhasan Enis , Sluckis Ben , Hammerman Ariel , Arbel Ronen
Published: December 2023

Introduction:
Semaglutide is a glucagon-like peptide-1 receptor agonist (GLP-1RA) indicated to reduce major adverse cardiovascular events (MACE) in patients with Type-2 Diabetes Mellitus (T2DM) and established cardiovascular disease. Tirzepatide is a novel glucose-dependent insulinotropic polypeptide (GIP) and GLP-1RA for the same purpose. Comparing the value for money of the two therapies in people with poorly controlled diabetes is essential for prioritization.

Methods:
We calculated the cost needed to prevent one MACE with either drug by multiplying the annualized number needed to treat (aNNT) to prevent one MACE by the annual cost of the therapy. Efficacy estimates were extracted from pre-specified cohorts of patients with an initial HbA1c above 8.5% in the SURPASS and SUSTAIN-6 trials. Drug costs were based on US GoodRx prices as of February 2023.

Results:
The aNNT to prevent one MACE in patients with an initial HbA1c of >8.5 with tirzepatide was 79 (95% CI: 44-∞) compared to 78 (95% CI: 42-∞) with semaglutide. The annual cost of tirzepatide is $13,286 versus $17,495 for semaglutide. Accordingly, the CNT to prevent one MACE with tirzepatide is $1,049,594 (95% CI: $584,584-∞) compared to $1,364,611 (95% CI: $734,790-∞) with semaglutide.

Conclusions:
Tirzepatide provides slightly better, but comparable, value for money than semaglutide when prescribed for secondary prevention of MACE in patients with an initial HbA1c >8.5.
Abstract 13489: Sex Differences in the Association of Multi-Ethnic Genome-Wide Systolic Blood Pressure Polygenic Risk Score With Hypertension
Authors: Shetty Naman S , Pampana Akhil , Patel Nirav , Peng Li , Yerabolu Krishin , Gaonkar Mokshad , Arora Garima , Arora Pankaj
Published: December 2023

Introduction:
Hypertension affects about half the US adult population with a higher prevalence in males. This study examines the contribution of the genetic architecture to the sex-associated differences in hypertension in a multi-ethnic US population.

Methods:
Multi-ancestry genome-wide association studies for systolic blood pressure (SBP) were conducted for each sex separately in the UK BioBank. Sex-specific SBP polygenic risk scores (SBP-PRS), comprising 1.1 million variants each, were generated from these GWASs. Sex-specific SBP-PRS was calculated in participants who underwent whole genome sequencing in the All of Us project. Based on the SBP-PRS, the cohort was stratified into low (<2.5
th
centile), low-intermediate (2.5
th
-20
th
centile), intermediate (20
th
-80
th
centile), high-intermediate (80
th
-97.5
th
centile), and high (>97.5
th
centile) genetic risk of SBP. Hypertension was defined as a BP ≥130/80 mmHg or anti-hypertensive use. Logistic regression models were used to assess the sex-stratified association of SBP-PRS with hypertension.

Results:
The All of Us cohort had 212,669 individuals [median age: 54 (38, 65) years] comprising 127,679 (60.0%) females and 97,600 (45.9%) non-White individuals (20.6% Black, 3.3% Asian, and 19.1% Hispanic). Hypertension was reported in 118,984 (55.9%) in the overall population and in 53,307 (62.7%) males and 65,677 (51.4%) females. Females [OR
adj
: 1.29 (1.27-1.30)] had higher odds of developing hypertension per SD increase in SBP PRS compared with males [OR
adj
: 1.22 (1.20-1.23)]. (P
interaction
:2.5x10
-6
) On stratification by SBP-PRS, females in the high-risk group and the low-risk group had higher odds of developing hypertension [OR
adj
: 1.81 (1.68-1.95) vs. 1.61 (1.46-1.74)] and lower odds of hypertension [OR
adj
: 0.52 (0.48-0.56) vs. 0.65 (0.60-0.71)], respectively compared with males.

Conclusion:
The contributions of the genetic underpinnings to the development of hypertension vary by sex.
Abstract 13509: Cardiovascular Outcomes in Metabolically Healthy Obese Asian-American Population Insights From a National Inpatient Sample
Authors: Mondal Avilash , LAPSIWALA BONEY , Perera Ayodya R , Rajpopat Pratik Bharat , Kodali Athri , Chenna Venkata Balaji , Nair Amritha , Iermolenko Valeriia , Gurumoorthy Rohini Bhuvaneshwari , Desai Brinda , Gnanaguruparan Subramanian , Desai Rupak
Published: December 2023

Background:
Cardio-metabolic risk factors usually predict major adverse cardio and cerebrovascular events (MACCE). However, outcomes in young metabolically healthy obese (MHO) Asian Americans (AA) have not been studied yet.

Methods:
Using the National Inpatient Sample (2019), we identified hospitalizations among young obese AA [aged 18-44] to obtain propensity-matched MHO+ and MHO- cohorts. Multivariable regression analyses were performed after controlling baseline demographic and comorbid variables to assess the risk of MACCE, including all-cause mortality, acute myocardial infarction, cardiac arrest, and stroke. Multivariable predictors of MACCE were also analyzed. P <0.05 was statistically significant.

Results:
Of total 327,065 young AA hospitalizations, 25,470 were obese. Propensity-matched cohorts of MHO+ (n=14,200) and MHO-(n=14,200) were comparable for demographics (Median age 32 years, females 85.9% vs 84.8%). After adjusting for baseline demographics and comorbidities, the odds of MACCE (aOR 0.98, 95%CI 0.70-1.37, p=0.886) were higher, and ACM (aOR 1.26, 95CI% 0.4-3.99, p=0.690) was lower in MHO+ compared to MHO- group however, it was not statistically significant. MHO patients also had higher rates for MACCE among males (OR 10.18, 95%Cl 3.39-30.53, p <0.001), drug abusers (OR 2.87, 95%Cl 1.05-7.86, p=0.04), cancer (OR 9.70, 95%Cl 2.14-44.01, p =0.003) and congenital circulatory anomalies (OR 21.77, 95Cl 4.07-116.60, p <0.001).

Conclusion:
Obese AA population without cardiometabolic risk factors define a subgroup of at-risk population with males, drug abusers, cancers, and congenital abnormalities pose an increased risk of adverse cardio and cerebrovascular events. Targeted interventions, early risk stratification, and preventive measures are warranted in these populations.
Abstract 13550: Prognostic Value of the Global Left Ventricular Contractility Index in Patients With Severe Mitral Regurgitation and Preserved Left Ventricular Ejection Fraction
Authors: Panday Vinay B , Lai Jessele , Gao Nicholas L , Lim Beth S , Leow Aloysius , Sia Ching-hui , Tan Ru San , Zhong Liang , Kong William , Poh Kian Keong
Published: December 2023

Introduction:
Global left ventricular (LV) contractility index,

dσ*/dt
max

, defined as the maximal rate of change of pressure-normalized LV wall stress, is given by the formula

3(dV/dt)
max
/2V
m

where

dV/dt
max

is the product of left ventricular outflow tract (LVOT) velocity and area; and

V
m

, left ventricular mass index (LVMI). In published reports, prediction of clinical outcomes in aortic stenosis were observed. It is unknown if

dσ*/dt
max

would predict clinical outcomes in patients with severe mitral regurgitation (MR).

Aim:
We studied the association of

dσ*/dt
max

with clinical outcomes in severe MR with preserved LV ejection fraction (EF).

Methods:
Consecutive patients with severe MR and LVEF ≥50% diagnosed on index echocardiogram at a single centre were retrospectively analyzed. Patients with other valvular lesions of moderate severity or more, or valvular interventions, were excluded. Clinical outcomes were ascertained by review of medical records. The primary outcome was a composite of heart failure hospitalizations and all-cause mortality.

Results:
176 patients were included in the analysis. Table 1 depicts the characteristics of the study population. Patients with composite outcomes were older, more likely to be female, had higher LVMI, lower regurgitation volume and

dσ*/dt
max

(2.2 +/- 0.7 vs 2.7 +/- 0.9, p = 0.02). On multivariable Cox regression (Table 2), only age and

dσ*/dt
max

(adjusted HR 0.42, 95% CI: 0.220 - 0.806, p = 0.01) remained independently associated with occurrence of the primary outcome.

Conclusions:
In patients with isolated severe mitral regurgitation and preserved LVEF, low

dσ*/dt
max

was an independent predictor of adverse clinical outcomes.
Abstract 13580: Impact of Chronic Kidney Disease on the Association of Ankle Brachial Index With Cardiovascular and All-Cause Mortality
Authors: Aurangzeb Fatima , Afridi Maryam , Waheed Salman
Published: December 2023

Introduction:
The association of low Ankle brachial index (ABI) with increased risk of cardiovascular (CV) as well as all-cause mortality is well established. Similarly, there is an independent association of chronic kidney disease (CKD) with CV and all-cause mortality. Little is known about the association of low ABI with CV and all-cause mortality by CKD status.

Methods:
We used data on 4,614 subjects from the National Health and Nutritional Examination Survey (NHANES) from January 1, 1999, to December 31, 2002. Those with available data on ABI and CKD status were included. Subjects were categorized as: 1) normal ABI (
>
0.9), no CKD (eGFR
>
60 ml/min/m
2
, reference), 2) normal ABI and CKD, 3) Abnormal ABI, no CKD, 4) Abnormal ABI and CKD. NHANES-linked National death index records were used to determine CV and all-cause mortality. We used Cox proportional-hazards models and controlled for age, race, gender, income, educational status, smoking history, diabetes, systolic blood pressure, HDL and total cholesterol levels and history of CV disease.

Results:
Mean age was 55.7 years with 51% females and 4% blacks. Low ABI was present in 7%, while 6.4% had CKD and 1.3% had both low ABI and CKD. Median follow-up was 10.3 years. ABI<0.9 was associated with risk of all-cause [Hazard ratio: 1.59 (95% confidence interval: 1.21-2.01)] and CV mortality [2.80 (1.72-4.56)] compared to normal ABI. Similarly, CKD was associated with risk of all-cause [1.34 (1.04-1.71)] and CV mortality [1.69 (1.0-2.96)] compared to no CKD. Among categories, the risk was [1.29 (0.9-1.8)], [1.57 (1.1-2.2)] and [1.92 (1.3-2.6)] for all cause mortality, and [1.2 (0.5-2.9)], [2.3 (1.3-4.0)] and [4.72, (2.6-8.4)] for CV mortality in groups normal ABI with CKD, abnormal ABI without CKD and abnormal ABI and CKD both, respectively compared to the reference group.

Conclusion:
Low ABI confers a much higher risk of CV and all-cause mortality in those with CKD than those without CKD. More aggressive risk factor modification might be warranted in those with CKD and low ABI to lower risk.
Abstract 136: Does End-Tidal Carbon Dioxide Measured at the Facial Mask Predict Return of Spontaneous Circulation in Out-of-Hospital Cardiac Arrest?
Authors: CASSUTO MARGOT , Ghouzali Ibtissem , Ozguler Anna , Baer Michel , Loeb Thomas
Published: December 2023

Introduction:
High value of end-tidal carbon dioxide (EtCO2), measured at the end of a tracheal tube, is closely associated with return of spontaneous circulation (ROSC) in out-of-hospital cardiac arrest (OHCA) resuscitation. The aim of this study was to evaluate whether EtCO2 measured at the face mask (FM) before an intubation procedure, may also predict ROSC in OHCA.

Material and Methods:
This was a prospective non-interventional study. Between May 1
st
2022 and January 30
th
2023, all patients ≥ 18 years with an OHCA on EMS arrival and for whom a laryngoscopy for tracheal intubation was considered, were included. An EtCO2 sensor was directly placed between the valve of the bag-valve-mask and the FM while cardiopulmonary resuscitation was continued. Age, gender, initial rhythm, ROSC on scene and last EtCO2 at the FM (FM-EtCO2) value before laryngoscopy were collected. Patients were assigned to 3 groups: FM-EtCO2 < 10 mmHg ; 10 mmHg
<
FM-EtCO2
<
30 mmHg and FM-EtCO2 > 30 mmHg.

Results:
Twenty-three patients were included. Mean age was 64.9 ± 12.2 years and sex ratio was 3.6. Initial rhythm was asystole for 16 (69.6 %) patients, ventricular fibrillation for 5 (21.7 %) and pulseless rhythm for 2 (8.7%). Eight (34.8 %) patients had a ROSC on scene. Five (21,8 %) patients had a FM-EtCO2 < 10 mmHg ; 7 (30,4%) a 10 mmHg
<
FM-EtCO2
<
30 mmHg and 11 (47,8 %) a FM-EtCO2 > 30 mmHg. Among those with a ROSC, 2 had a FM-EtCO2 < 10 mmHg and 6 a FM-EtCO2 > 30 mmHg (p=0,038).

Conclusion:
A high value of EtCO2 measured at the face mask (above 30mmHg) was significantly associated with ROSC. This survey proposes a method that would facilitate the knowledge of an EtCO2 value, well known to predict ROSC in OHCA, earlier than with the reference method. Further studies are needed to validate these results.
Abstract 13703: Left Ventricular Assist Device Therapy in “Cold and Dry” Patients
Authors: Balgobind Amrita , Varrias Dimitrios , Patel Snehal R , SAFIRIYU ISRAEL , Spanos Michail , Alvarez Villela Miguel
Published: December 2023

Introduction:
Patients who suffer from end-stage HF and have low PCWP are referred to as “cold and dry” patients and are an understudied minority, where the benefit derived from LVAD therapy is unclear. We therefore conducted a retrospective analysis to evaluate functional outcomes and quality of life after LVAD in patients with low versus high PCWP on pre-LVAD hemodynamics.

Methods:
Adults receiving LVADs between 2006 and 2017 were identified from the INTERMACS database. Outcomes include assessment of functional status with 6-minute walk test (6MWT) distance and quality of life measures, with KCCQ and EuroQol questionnaire scores pre- and post-LVAD, stratified by pre-LVAD PCWP. Median follow up was 364±41 days.

Results:
Study sample comprised 10310 patients who received LVAD from 2006 to 2017. Mean age was 57 ± 13, 8113 (79%) were male, and the mean PCWP prior to LVAD implantation was 25 ± 9.19 mmHg. The patients were separated into a high (PCWP >15 mmHg) and a low (PCWP<15 mmHg) group based on pre-LVAD hemodynamics. For patients with PCWP <15 mmHg, mean age was 58.1±12.4, 1191 (74%) were males, LVEDD was 6.7±1 cm, and mean PCWP was 11±3.2 mmHg (Table 1). When compared to patients with high PWCP, those with a PCWP <15 mmHg showed less improvement in quality of life questionnaire scores, including EuroQol (+0.11 vs +0.17, p=0.001) and KCCQ (+26 vs +31, p=0.03), and functional capacity with 6MWT distance (+194 feet vs +340 feet, p=0.02) after LVAD (Figure 1).

Conclusions:
In patients with end-stage HF and low PCWP, LVADs are associated with less improvement in functional capacity and quality of life when compared to patients with high PCWP.
Abstract 13710: Cardiac Platypnea-Orthodeoxia Syndrome: How the Stars Aligned
Authors: Hamilton Steven A , Tobler Diana L , Bobrowsky Kevin , Ku Ivy A , Romero Alicia
Published: December 2023

Case description:
A 79-year-old man with recurrent falls, dyslipidemia and recent exercise intolerance presented after a fall. He was putting on shoes, lost his balance and fell. There was no pre-syncope, syncope, dyspnea, chest pain, palpitations or dizziness. On admission, vital signs were normal except oxygen saturation (O2 sat) 79% on room air (and no improvement with supplemental O2). An arterial blood gas (ABG) revealed partial pressure of oxygen 42 mmHg with oxygen saturation 80%. He had lower thoracic spine tenderness, normal respiratory and cardiac exam. CT head showed no acute intracranial abnormalities. CTA chest had no pulmonary embolism, arterio-venous malformations or parenchymal lung disease. There was a thoracic aorta aneurysm (4.5cm at aortic root and 5.1cm at posterior arch). Subsequently, O2 sat was 92% supine and 79% standing. He also had a compression fracture of T12 and spinal asymmetry. A transesophageal echocardiogram (TEE) showed an aneurysmal, hypermobile interatrial septum with early right to left shunt with agitated saline due to a large patent foramen ovale (PFO). Right heart catheterization revealed no pulmonary hypertension and confirmed a step down from the pulmonary vein to left atrium (delta O2 sat 6%). A 30mm Gore Cardioform occluder was used to close the defect and immediately supplemental oxygen was removed, and O2 sat on room air was 95%. Follow up echocardiogram showed no residual shunt and exercise intolerance resolved.

Discussion:
Unexplained positional hypoxemia raised our suspicion for cardiac POS. Hypoxemia is caused by right to left shunting via the PFO, exacerbated by the thoracic aortic aneurysm and spinal changes such as the T12 fracture and spinal asymmetry. Going from being recumbent to erect there is stretching of the atria causing his PFO to enlarge, increasing the shunt. Additionally, the dilated thoracic aorta exerts mechanical pressure on the right atrium (RA) and interatrial septum, increasing PFO patency and augmenting flow from the inferior vena cava through the PFO. The spinal abnormality may cause more aortic distortion and exert forces on the RA, exacerbating shunting. Percutaneous PFO closure is the treatment of choice with closure immediately leading to significant improvement of hypoxemia.
Abstract 13712: Imaging Short-Chain Fatty Acid Metabolism and Transport in the Failing Heart by PET
Authors: Azcona Juan A , Wacker Anja , Lee Chul-Hee , Singh Pradeep K , Manzo Onorina , Di Lorenzo Annarita , Jeitner Thomas , Babich John , Amor-Coarasa Alejandro , Kelly James
Published: December 2023

Introduction:
Heart failure compromises the transport and oxidation of long chain fatty acids. Cardiomyocytes can compensate by using short-chain fatty acids (SCFA) which rely on other transport mechanisms. Based on this principle, we used 2-[
18
F]fluoropropionic acid ([
18
F]FPA), a radiolabeled SCFA analog, to assess these metabolic changes and image them by positron emission tomography (PET) in a doxorubicin-induced mouse model of cardiotoxicity.

Hypothesis:
We hypothesize that the increased demand for SCFA by the failing heart promotes cardiac accumulation of [
18
F]FPA which can be imaged by PET.

Methods:
[
18
F]FPA was injected intravenously into male C57BL/6J mice 10 weeks following intraperitoneal injections of 8 x 3 mg/kg doxorubicin (DOX). Dynamic PET acquisitions were performed from 60-120 min post injection of 9.25-11 MBq [
18
F]FPA. These images were acquired in the presence or absence of 5 mg/kg AZD3965, an inhibitor of monocarboxylate transporters. Heart uptake of [
18
F]FPA was determined by image-based quantitation and confirmed by a biodistribution study. Mechanistic [
18
F]FPA uptake studies were also conducted in primary human cardiomyocyte (HCM) cultures.

Results:
Mice experiencing DOX-induced cardiotoxicity exhibited statistically significant increases in cardiac [
18
F]FPA. AZD3965 did not significantly alter cardiac uptake but reduced uptake in all other tissues except the kidneys, the route of excretion. Additionally, [
18
F]FPA uptake is lost in HCM for which mitochondrial acyl-CoA synthetase (ACSS) 1, but not cytosolic ACSS2, is inhibited.

Conclusions:
Our findings present both mechanistic and translational applications for [
18
F]FPA. AZD3965 effectively reduced [
18
F]FPA uptake in other tissues except for the heart and can therefore be co-administered to enhance the heart-to-background ratio. Altogether, our results indicate that [
18
F]FPA may enter cardiac tissues by diffusion and become metabolically trapped in mitochondria.
Abstract 13713: Coronary Endothelial Dysfunction and Microvascular Vasospasm in Patients With Postural Orthostatic Tachycardia Syndrome
Authors: Steinberg Rebecca S , Dragan Anamaria , Mehta Puja K , Cutchins Alexis , Toleva Olga
Published: December 2023

Background:
Postural Orthostatic Tachycardia Syndrome (POTS) is characterized by autonomic dysfunction-related symptoms such as orthostatic intolerance, palpitations, dizziness, and chest pain. The mechanisms driving chest pain in POTS are unclear.

Hypothesis:
We hypothesized that coronary endothelial dysfunction (ED) and abnormal microvascular reactivity may be a contributor to chest pain in POTS.

Methods:
Patients (n=6) were diagnosed with POTS or had significant tachycardia despite medical therapy out of 67 patients in our cohort. All patients reported persistent chest pain and were referred for coronary function testing (CFT) to test macro- and micro-vascular function. CFT was performed to test endothelium-dependent and non-endothelium dependent function using graded doses of intracoronary acetylcholine (ACH), and intravenous adenosine (ADO). Coronary Flow Reserve<2.0 and Index of Microvascular Resistance>25 diagnosed coronary microvascular dysfunction. Coronary artery diameter narrowing to ACH (100 mcg) was used to diagnose ED. Epicardial coronary spasm was defined as >90% constriction to ACH. Microvascular spasm was diagnosed by ACH provoked-chest pain and EKG changes in the absence of epicardial spasm.

Results:
Mean age was 44.1 ± 15.2 years, 67% were female, and all tolerated CFT without complications. POTS symptoms, baseline medications, and CFT results are shown (
Table
). All had an abnormal response to ACH, indicating ED and microvascular spasm. Non-endothelium function was normal in all patients. Anti-anginal medications were changed based on CFT information, with improvement in chest pain with calcium channel blocker use.

Conclusion:
In all 6 pts, CP was associated with ED and microvascular spasm. Mechanistic links between ED and POTS need further investigation. Given that ED is a prognostic marker associated with recurrent angina hospitalization and events, investigation of therapies that target ED in POTS may be warranted.
Abstract 13719: Minimal and Delayed Age-Related Increase of Arterial Stiffness Among Tsimane Forager-Horticulturalists
Authors: Cao Tianyu , Cortez Edhitt C , Miyamoto Michael I , Cummings Daniel , Trumble Benjamin C , Stieglitz Jonathan , Thompson Randall C , Kaplan Hillard , Thomas Gregory S , Duprez Daniel A , Jacobs David R , Gurven Michael
Published: December 2023

Background:
Tsimane forager-farmers of the Bolivian Amazon exhibit a distinct trajectory of vascular aging, characterized by low age-related increases in BP, the lowest levels of coronary calcification ever reported, and robust VO
2
max. However, the prevalence of arterial stiffness (ArSt) in this population and its association with age and other cardiovascular risk factors are unknown.

Methods:
Large artery elasticity (LAE) and small artery elasticity (SAE) were measured among 491 Tsimane adults (mean age 55.3±13.0 y, 55% female) using HDI CR-2000 (Eagan, MN). Carotid-femoral pulse wave velocity (cfPWV) was assessed among 89 Tsimane (mean age 53.1±15.7 y, 54% female) using the foot-to-foot method with ECG and carotid/femoral pulse wave data.

Results:
Compared to previous studies from diverse urban populations, Tsimane show lower indices of ArSt: higher LAE (mean 22.79±12.21 ml/mmHg·10) and SAE (mean 7.57±4.04 ml/mmHg·100), and lower cfPWV (mean 6.34±2.1 m/s). LAE and SAE are 73% and 57% higher for Tsimane men, and 70% and 86% higher for Tsimane women, compared to age-matched US MESA adults. Tsimane demonstrate lower LAE and SAE with age, while higher cfPWV was only evident among Tsimane over 70 years (β=2.26±0.71,
P
=0.001; reference <40 y). Hypertension is rare in this population, but was associated with having higher ArSt.

Conclusion:
Tsimane forager-farmers have substantially lower levels of ArSt and fewer age-related differences in ArSt compared to more urbanized and sedentary populations. The minimal and delayed age-related increase of arterial stiffness might contribute to the very low observed levels of coronary atherosclerosis and dementia in the Tsimane.
Abstract 13736: Whole Body versus Small Muscle Mass Exercise Training in Patients With Heart Failure With Preserved Ejection Fraction: Impact on Peripheral Responses to Exercise
Authors: Skow Rachel , Hearon Christopher , Sarma Satyam , MacNamara James , Samels Mitchel , Fadel Paul J , Levine Benjamin D , Haykowsky Mark J
Published: December 2023

Background:
Patients with heart failure with preserved ejection fraction (HFpEF) have reduced peak aerobic power (VO
2
) during whole body exercise due in part to smaller increases in blood flow (BF) and arterial-to-venous oxygen difference (Δa-vO
2
). We recently demonstrated that 8wks of single leg knee extension (SLKE) exercise training was effective in improving whole body VO
2
by increasing Δa-vO
2
in HFpEF; whether SLKE training induces greater peripheral adaptations compared to traditionally prescribed whole-body (i.e., cycle) training is unknown.

Hypothesis:
SLKE training will result in larger improvements in peak leg VO
2
, leg BF, and Δa-vO
2
during a SLKE peak exercise test vs cycle training.

Methods:
We recruited 16 patients with HFpEF (71 ± 6yr, 5 males) and randomized them to cycle or SLKE training 3-4 days/wk for 16wk. Before and after the intervention we quantified leg BF (ultrasound), femoral venous O
2
partial pressure (PvO
2
) and saturation (IV catheter) during incremental SLKE peak exercise to determine peak leg VO
2,
Δa-vO
2,
and skeletal muscle diffusive conductance (DMO
2
; leg VO
2
/[2x leg PvO
2
]).

Results:
SLKE (n=9) and cycle (n=7) groups were matched for age and sex. Both groups increased peak workload during the SLKE exercise test (34±8%; mean ± SE; p=0.005). There was a main effect of training such that peak DMO
2
improved in both groups (cycle: 45±19%; SLKE: 12±3%; see
Figure 1
). Peak Δa-vO
2
also improved (main effect of training, p=0.002); however, this was greater in response to cycle compared to SLKE training (12±3% vs 3±2%; interaction effect, p=0.035).

Conclusion:
These preliminary data indicate that both types of training improve leg DMO
2
; however, greater improvements in O
2
extraction occurred with cycle training. The differences in the peripheral adaptations may be attributed to a larger exercise “dose” in the cycle trained group. This data highlights that both modalities are effective components of exercise prescription for patients with HFpEF.
Abstract 13741: Off-Label Dosing of Direct Oral Anticoagulants Among Inpatients With Atrial Fibrillation
Authors: Sandhu Amneet , Kaltenbach Lisa , Chiswell Karen , Shimoga Vijay , Ashur Carmel , Pribish Abby , Fonarow Gregg C , Piccini Jonathan P , Ho Michael , Varosy Paul D , Hess Paul
Published: December 2023

Introduction:
Among patients hospitalized for atrial fibrillation (AF), the frequency of off-label direct oral anticoagulant (DOAC) dosing, associated factors, hospital-level variation, and temporal trends in contemporary practice are unknown.

Methods:
Using the Get With The Guidelines® Atrial Fibrillation (GWTG-AF) registry, patients admitted from January 1
st
, 2014 to March 31
st
, 2020, and discharged on DOAC were stratified according to receipt of under, over, or recommended dose. Factors associated with off-label dosing were identified using logistic regression. Hospital-level variation and temporal trends were assessed.

Results:
Of 22,470 patients prescribed a DOAC at discharge from hospitalization (66% apixaban, 29% rivaroxaban, 5% dabigatran), underdosing occurred among 2006 (8.9%), overdosing among 511 (2.3%), and recommended dosing among 19953 (88.8%). Patient factors associated with off-label use included age (underdosing: OR 1.06 per 1-year increase [95% CI 1.06-1.07] and overdosing: OR 1.07 per 1-year increase [1.06-1.09]), dialysis dependence (underdosing: OR 5.50 [3.76-8.05] and overdosing: OR 5.47 [2.74-10.88]), female sex (overdosing: OR 0.79 [0.63-0.99]) and weight (overdosing: OR 0.96 per 1-Kg increase [0.95-1.00]). Across hospitals, the adjusted median odds ratio for off-label DOAC use was 1.45 [95% CI 1.34-1.65] (underdosing: 1.52 [1.39-1.76] and overdosing: 1.32 [1.20-1.84]), indicating significant hospital-level variation. Hospital characteristics associated with underdosing included West vs. Northeast location (OR: 1.55 [1.04-2.31]), rural vs. urban setting (OR: 0.48 [0.28-0.83]), and number of beds (<200 vs. 500+, OR: 1.95 [1.29-2.95]). Recommended dosing significantly increased over time (81.9% in 2014 to 90.9% in 2020, p<0.0001 for trend) with a corresponding decline in under (14.4% in 2014 to 6.6% in 2020, p<0.0001 for trend) and overdosing (3.8% in 2014 to 2.5% in 2020, p=0.001 for trend).

Conclusion:
One of 10 patients hospitalized for atrial fibrillation is discharged on off-label dosing of DOAC with significant variation across hospitals. While the proportion of patients receiving recommended dosing has significantly improved over time, opportunities to improve DOAC dosing persist.
Abstract 13745: Exploring the Segment-Wise Explainability of Electrocardiogram on Deep Learning-Based Models for Acute Myocardial Infarction
Authors: Ji Younghoon , Cho Kyung Hoon , Chang Mineok , Joo Sunghoon , Park Minje , Kim Kyung Geun , Lee Yeha , Kim Min Chul , Sim Doo Sun , Hong Young Joon , kim Juhan , Ahn Young Keun , Jeong Myung Ho , Shin Dong-Geum , Cho Jung Rae , Kang Min-Kyung , Seonghoon Choi , Lee Namho , Han Donghoon
Published: December 2023

Background:
While DL models for AMI detection using ECGs have advanced, their 'black box' nature hinders seamless integration into clinical practice, as it limits our understanding of their decision-making process.

Research Questions:
Which specific ECG segments (P, QRS, T) are considered important by the DL model for the detecting AMI, and does it fit into the ECG criteria of AMI?

Aims:
We aimed to examine the importance of each ECG segment in the detection of DL model for AMI.

Methods:
We examined the impact of various ECG segments by replacing their values with Gaussian noise and verify the decrease in AUC of a DL model for detecting AMI. The importance of each ECG segment in diagnosing AMI using a DL model was assessed by observing the performance drop in AUC of the model. DL-based model detecting AMI trained with 17,907 ECGs from 5,872 coronary angiography-validated AMI patients and 705,482 ECGs from 294,755 non-AMI patients at Chonnam National University Hospital (May 2013 - December 2020). External validation was performed at Hallym University Kangnam Sacred Heart Hospital using 357,072 ECGs from 163,870 patients (January 2006 - December 2020). For ECG segmentation, a U-Net architecture trained on LUDB was employed.

Results:
The test set was divided into STEMI and NSTEMI groups within internal and external sets. The occurrence rates of events in ECGs were 0.498% (1895/380149) for STEMI and 0.67% (2550/380804) for NSTEMI. In the STEMI group, the AUC values were as follows: 12-lead raw ECG - 0.988, P-wave masking ECG - 0.986, QRS-complex masking ECG - 0.943, and T-wave masking ECG - 0.939. In the NSTEMI group, the AUC values were 0.943, 0.936, 0.835, and 0.867, respectively.

Conclusion:
The DL model assigns varying degrees of importance to individual ECG segments when determining AMI. The results show that the AMI model effectively utilizes ECG characteristics such as QRS and T waves, which are also highly valued in clinical practice, to determine the presence of AMI.
Abstract 13778: Effects of Omega-3 Fatty Acid Supplementation on Revascularization and Major Cardiovascular Events: A Systematic Review and Meta-Analysis
Authors: Sofi Francesco , Dinu Monica , Lotti Sofia , Genovese Luca , Mattioli Anna Vittor , Ambrosio Giuseppe
Published: December 2023

Background:
Benefits of omega-3 administration in preventing cardiovascular (CV) events are controversial. In particular, while statins have been associated with significant reduction of revascularizations (Revasc), effects of omega-3 on Revasc are unclear.

Aim:
To metanalyze evidence on the effect of omega-3 administration on incident Revasc and CV events (myocardial infarction [MI], stroke, heart failure [HF], CV death).

Methods:
We searched MEDLINE, Embase, Scopus, Web-of-Science and Cochrane Library for randomized controlled trials (RCTs) with ≥500 participants comparing the effects of omega-3 formulations [decosahexanoic acid+eicosapentaenoic acid (DHA+EPA) or EPA alone] versus placebo.

Results:
Seventeen RCTs with participants (both primary and secondary CV prevention) randomized to DHA+EPA (n=52,498) or EPA alone (n=13,415) and controls (n=65,771) were included. Follow-up ranged from 4.5 months to 7.4 years. Significant heterogeneity emerged among studies (Figure). Overall, compared to controls omega-3 supplementation was associated with reduced risk of Revasc (Figure) and MI [0.89, 95% CI 0.80-0.98; p

heter

=0.04; I
2
=45%; p=0.02] with no significant effect on stroke, HF, and CV death. Reduced risk of Revasc was still observed when most (≥60%) participants were already on statins (Figure). Compared to DHA+EPA, EPA alone was associated with a greater reduced risk of Revasc (Figure) and stroke [0.72, 95% CI 0.55-0.95], with no significant effect on HF and CV death. No significant differences were observed for DHA+EPA dose ≤0.9g/day vs >0.9g/day, or EPA alone ≤0.7 g/day vs >0.7 g/day.

Conclusions:
Omega-3 supplementation resulted in reduced risk of Revascularization, unaffected by background statin use. Use of EPA alone appeared to be associated with even greater benefits. Further studies are needed to clarify the role of omega-3 supplementation in preventing hard CV events
Abstract 13901: Deep Learning-Based Digital Biomarker to Diagnose Hypertension and Stratify Cardiovascular Risk From the Electrocardiogram
Authors: Al-Alusi Mostafa A , Friedman Samuel , Kany Shinwan , Ramo Joel , Pipilas Daniel , Singh Pulkit , Reeder Christopher , Khurshid Shaan , Pirruccello James , Maddah Mahnaz , Ho Jennifer E , Ellinor Patrick T
Published: December 2023

Background/Aim:
Hypertension affects nearly half of US adults and is a major modifiable risk factor for cardiovascular disease (CVD). Guidelines recommend serial blood pressure (BP) measurement under controlled conditions or ambulatory BP monitoring, but BP is often measured intermittently under suboptimal conditions, leading to underdiagnosis and undertreatment. We developed a deep learning model (HTN-AI) to identify hypertension and stratify risk of hypertension-associated CVD from 12-lead ECGs.

Methods:
HTN-AI is a convolutional neural network trained to detect prevalent hypertension or elevated baseline BP (systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg) using 747,992 ECGs from 106,879 adults receiving primary or cardiology care at Massachusetts General Hospital (MGH). Associations between HTN-AI-predicted risk of hypertension and CVD (all-cause mortality, heart failure [HF], myocardial infarction [MI], stroke, and aortic dissection) were assessed in 56,730 primary care patients at Brigham and Women’s Hospital (BWH) with cumulative incidence analysis and cause-specific hazard regression.

Results:
In an MGH test sample and the BWH sample, HTN-AI discriminated prevalent hypertension or elevated baseline BP (AUC 0.791 and 0.762, respectively). Quintiles of HTN-AI risk stratified cumulative incidence of mortality (Figure), HF, MI, stroke, and aortic dissection (p < 0.001 for all). HTN-AI risk was significantly associated with age- and sex-adjusted risk of incident mortality (HR per SD: 1.85 [95% CI: 1.77-1.92], p<0.001), HF (3.55 [3.25-3.88], p<0.001), MI (2.33 [2.20-2.47], p<0.001), stroke (1.74 [1.64-1.86], p<0.001), and aortic dissection (1.80 [1.41-2.31], p<0.001).

Conclusion:
A deep learning model, HTN-AI, discriminates patients with hypertension and stratifies risk of incident CVD using 12-lead ECGs. HTN-AI has the potential to facilitate diagnosis of hypertension and serve as a novel digital biomarker for hypertension-associated CVD.
Abstract 13904: Association Between Pre-Ablation and Post-Ablation Neutrophil-Lymphocyte Ratio and Atrial Fibrillation Recurrence: A Meta-Analysis
Authors: Lekkala Sai Prasanna , Mellacheruvu Sai Priyanka , Jitta Sahas Reddy , Chigurupati Himaja Dutt , Neppala Sivaram , Singh Gurjot , Khela Puneeteshwar , Patel Manali , Pamreddy Hrushikesh Reddy , Kannekanti Lavanya chowdary , Gill Karanvir Singh , Hingora Mohmed Junaid , Desai Rupak
Published: December 2023

Introduction:
Recurrence of atrial fibrillation (AF) has become prevalent in patients who have had catheter ablation. A high neutrophil-lymphocyte ratio (NLR) may predict the risk of AF recurrence. However, the research is inconclusive. This meta-analysis examined the importance of easy access and cost-effective pre and post-ablation NLR values as predictors of AF recurrence in post-ablation patients.

Methods:
We conducted a literature search in PubMed, SCOPUS, and Google Scholar to identify the relevant studies through May 2023. Random effects models were employed to estimate the pooled odds ratio (OR) of pre and post-NLR and AF recurrence. I2 statistics and leave-one-out sensitivity analysis were used to report inter-study heterogeneity. p<0.05 was significant.

Results:
We retrieved 270 studies from the literature search, and seven studies were included in this meta-analysis, in which 1983 participants who had AF recurrence after undergoing ablation were analyzed. There are 5 retrospective and 2 prospective studies with a mean follow-up of 20.5 months. The pooled analysis showed the unadjusted odds ratio (OR) of AF recurrence for pre-ablation NLR as 1.33 (95% CI: 1.04-1.71, p<0.01, I2 = 95.49%) and the adjusted OR as 1.45 (95% CI: 0.87-2.43, p<0.01, I2 = 95.1%) (Fig. 1). For post-ablation NLR, the unadjusted OR was 1.21 (95% CI:1.09-1.36, p<0.01, I2 = 85.9%), and the adjusted OR was 1.28 (95% CI: 0.93-1.76), demonstrating significant heterogeneity (I2 =95.32%) with a p-value of <0.01 (Fig.1).

Conclusion:
NLR had a significant association with predicting the recurrence of AF. We recommend clinicians add a simple NLR blood test to their diagnostic modalities to detect AF recurrence.
Abstract 13917: Predictors of Ventricular Arrhythmias in Patients With Left Ventricular Ejection Fraction Improvement to >35% Following Cardiac Resynchronization Therapy
Authors: Sherazi Saadia , Goldenberg Ilan , McNitt Scott , Rao Nikhila , Rao Nilesh , Shah Ahmed A , Aktas Mehmet K , Kutyifa Valentina , Zareba Wojciech , Rao Krishna
Published: December 2023

Introduction:
Patients undergoing cardiac resynchronization therapy with a defibrillator (CRT-D) show significant improvement in LVEF. We designed this study to identify predictors of ventricular arrhythmic (VA) events among patient with LVEF improvement > 35% after one year of treatment with CRT-D.

Hypothesis:
We hypothesized that LVEF improvement > 35% is associated with a decreased risk of VA events.

Methods:
Patients randomized to CRT-defibrillator from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) trial with LVEF > 35% at 12 months were included in this analysis (N=651). Predictors of an appropriate ICD therapy for VA subsequent to one year were evaluated by cox regression model. Cumulative probability of first event was analyzed by Kaplan Meier Method with time for follow-up beginning at 1 year after device implantation.

Results:
The average follow-up was 2.04 ± 0.83 years. We identified 3 independent predictors of VA among patients treated with CRT-D subsequent to LVEF improvement to > 35%: (1) baseline non-LBBB morphology (HR=1.93; 95% CI,1.23-3.04; p= 0.004); (2) the occurrence of VA during first year post CRT-D implant (HR=4.91 [95% CI, 2.99-8.07]; p<0.001); and (3) lower range improvement in LVEF (36-40% vs. >40%; HR =1.97 [95% CI 1.21-3.20]; p= 0.006). When compared with patients with 0 risk factors, having one and 2 or more risk factors had significantly higher risk of VTA (2-year rate of VT/VF = 4%, 11% and 32% respectively; HRs = 2.9 [p=0.002]and 7.9 [p=<0.001], respectively [Figure]).

Conclusions:
We identify a sub-group of patients who remain at high risk of VTA despite improvement in LVEF > 35% with CRT-D. Having a baseline non-LBBB morphology, experiencing VA during the first year post CRT-D, and lower-range LVEF improvement are associated with high risk of future arrhythmias, with a cumulative effect.
Abstract 13944: The Efficacy and Safety of New Potassium Binders on RASSi Optimization in Hyperkalemic Patients With Heart Failure: A Systematic-Review and Meta-Analysis of Randomized Controlled Trials
Authors: Abuelazm Mohamed T , badr amr T , Atef Mostafa , Turkmani Mustafa , Amin Ahmed Mazen , Aboutaleb AYA , Gowaily Ibrahim , Abdelazeem Basel
Published: December 2023

Introduction:
Guideline-directed medical therapy (GDMT) has improved outcomes in patients with heart failure (HF), including the use of renin-angiotensin-aldosterone system inhibitors (RAASi); angiotensin-converting enzyme inhibitors (ACEis), angiotensin receptor blockers (ARBs), angiotensin receptor/neprilysin inhibitor (ANRi), and mineralocorticoid receptor antagonists (MRAs). RAASi can hinder the excretion of potassium, resulting in hyperkalemia. New potassium binders (NPB) (patiromer and sodium zirconium cyclosilicate) can prevent this adverse effect; however, the efficacy and safety of NPB for this indication have not been fully established.

Methods:
We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching: PubMed, Web of Science, SCOPUS, and Cochrane through April 26th, 2023. We used the fixed-effect model to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD), with a 95% confidence interval (CI).

Results:
We included five RCTs with a total of 1,399 patients. BPB was significantly associated with successful MRA optimization (RR: 1.13 with 95% CI [1.02, 1.25], P=0.02), decreased patients with MRA at less than target dose (RR: 0.72 with 95% CI [0.57, 0.90], P=0.004), and decreased hyperkalemic episodes (RR: 0.50 with 95% CI [0.32, 0.79], P=0.003). However, there was no difference between NPB and placebo regarding ACEi/ARB/ANRi optimization (RR: 1.02 with 95% CI [0.89, 1.17], P=0.76) and serum potassium change (MD: -0.31 with 95% CI [-0.61, 0.00], P=0.05).

Conclusion:
NPB can successfully improve GDMT outcomes by enhancing MRA optimization and decreasing hyperkalemic episodes. However, data regarding the NPB effect on ACEi/ARB/ANRi optimization remain scarce. Therefore, future RCTs should investigate it and conduct a head-to-head comparison of NPB.
Abstract 13945: Evaluation of a Deep Neural Network for Detection of D-Transposition of the Great Arteries on Fetal Echocardiograms
Authors: Arunamata Alisa , LEVY Marilyne , stos Bertrand , Askinazi Eric , Thorey Valentin , Gardella Christophe
Published: December 2023

Introduction:
While prenatal detection of congenital heart disease (CHD) has improved over the years, a significant proportion of CHD remains unrecognized on fetal ultrasound. Prenatal identification of d-transposition of the great arteries (d-TGA) in particular would significantly alter delivery planning and postnatal course.

Research Questions:
We investigated whether a deep neural network (DNN) can accurately detect d-TGA on fetal echocardiograms.

Aim:
To evaluate a DNN for detection of d-TGA on second (2T) or third (3T) trimester fetal echocardiograms.

Methods:
Patients with a singleton pregnancy with a 2T or 3T fetal echocardiogram performed between Jan 1, 2022 and May 1, 2023 at one center were retrospectively evaluated. Cases of d-TGA and negative cases referred for family history of CHD or increased nuchal translucency were included. Cases were reviewed by 3 pediatric cardiologists to confirm that the recorded ultrasound clips were sufficient to diagnose the presence or absence of d-TGA, and were excluded otherwise.

The DNN was trained on patients not included in the evaluation to detect the absence of the great artery cross-over pattern, a distinct finding in d-TGA. The DNN outputs the presence or absence of this finding using all recorded video clips of an examination.

Results:
We included 18 positive and 99 negative cases. The DNN detected suspicion for d-TGA with an AUC of 91.4%, sensitivity of 83.3% (60.8-94.2, 95%CI) and specificity of 92.9% (86.1-96.5, 95%CI).

Conclusions:
D-TGA can be accurately detected on fetal echocardiograms using a DNN. These promising results lay the foundation for reliable, computer-aided detection of CHD on screening fetal ultrasounds.