bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 6982: PCI Appropriateness of Use: Trends Over the Last Decade
Authors: Rawal Harsh , Nguyen Tung , Klein Lloyd W
Published: April 2024

Introduction:
The Appropriate Use Criteria (AUC) for coronary revascularization have undergone 2 revisions, reflecting improved understanding of which situations percutaneous coronary intervention (PCI) optimizes patient care. Over this time, PCI appropriateness and volumes have changed with increased compliance. Accordingly, we analyzed these changes in detail.

Methods:
PubMed and Embase libraries identified 9 national studies evaluating appropriate use of PCI. Case appropriateness was classified as appropriate, inappropriate/rarely appropriate, uncertain/may be appropriate and unmappable. Temporal trends for each category were determined from linear regression. Student-t-test was used to compare groups using Graphpad Prism 8.0 software.

Results:
The total number of PCIs decreased 14.1% over the study period. This diminished volume was associated with reductions in both non-acute (from 22.5% to 16.3%, p <0.01) and non-mappable PCIs (from 17.6% to 5.0%, p<0.001), while acute PCIs increased (from 65.7% to 81.2%, p<0.001, figure). In non-acute PCIs, appropriate PCIs increased (from 42.8% to 68.4%, p<0.001) while both inappropriate (from 18.9% to 11.6%, p<0.01) and uncertain (from 38.2% to 20.0%, p<0.001) were reduced. Reclassification as defined in the 2017 Revision led to significant decrease in appropriate (56.8% to 48.0%, p<0.01) and an increase in uncertain class (32.7% to 50.1%, p <0.01). Acute PCIs showed no overall change in appropriateness.

Conclusions:
These findings demonstrate: 1) the overall volume of PCIs is decreasing, 2) revised classification led to more uncertain PCIs, and 3) the percent of appropriate non-acute PCIs is increasing with a decline in inappropriate and uncertain PCI. The AUC have successfully decreased the performance of inappropriate/rarely appropriate PCIs. These trends suggest either that more appropriate non-acute PCIs are being performed or better documentation has led to more accurate classification.
Abstract 6991: Impaired Systemic Oxygen Extraction Relates to Reduced Exercise Capacity in Post-COVID-19 Long Hauler Syndrome
Authors: Biondi Max J , Joseph Phillip , Gulati Mridu , Possick Jennifer , Lutchmansingh Denyse , Cullinan Marjorie , Heerdt Paul M , Singh Inderjit
Published: April 2024

Introduction:
Following acute coronavirus 2019 (COVID-19) disease, at least 10% of patients report some form of residual limitation, most commonly dyspnea and fatigue. These COVID-19 “long haulers” experience symptoms that are largely unexplained by pulmonary function testing (PFT), echocardiogram and chest computed tomography (CT). Using invasive cardiopulmonary exercise testing, this pilot study characterized exercise limitation in 5 patients with persistent symptoms 1 year following mild COVID-19 illness.

Methods:
Following written informed consent, data were obtained in accordance with an IRB-approved protocol entailing placement of radial and pulmonary arterial catheters for pressure monitoring and blood sampling prior to and during maximum upright incremental exercise. Rest and exercise pulmonary hemodynamics, ventilation and gas exchange were recorded. Aerobic exercise capacity was estimated by peak O
2
consumption (VO
2
).

Results:
All patients had normal biventricular and valvular function on resting echocardiogram, no evident parenchymal lung disease on CT, and normal PFTs. Resting mean pulmonary arterial pressure was ≤20 mmHg for all patients with pulmonary vascular resistance <3 Woods units. At maximum exercise, all patients exhibited normal respiratory, cardiac output (% predicted), and total pulmonary vascular resistance responses, but demonstrated clearly depressed aerobic capacity (peak VO
2
<80% predicted). Reduced peak VO
2
was associated with impaired systemic O
2
extraction as indicated by an arterial-venous O
2
content difference (adjusted for hemoglobin) of <80% (
Figure 1
).

Conclusion:
This case series provides preliminary evidence that reduced peak aerobic capacity among long haulers is primarily attributable to a peripheral (i.e., impaired systemic O
2
extraction), rather than central cardiopulmonary, limitation. These results suggest that systemic microcirculatory dysfunction contributes to exercise limitation.
Abstract 8868: Impact of Obesity on Sinus Nodal Dysfunction - A Retrospective National Database Study
Authors: Aljadah Michael , Shaka Hafeez , Kichloo Asim , Elamir Zain , DeHart Luke , Albosta Michael , Velazquez Genaro , ASEMOTA IRIAGBONSE , Akuna Emmanuel , Mohiuddin Khalid , kanjwal khalil
Published: April 2024

Introduction:
Sick sinus syndrome (SSS) or sinus node dysfunction (SND) is degenerative disease of the sinus node. Previous research lacks objective data on the relationship between obesity and SND, with respect to inpatient mortality. This study aimed to discern a difference in mortality by using the National Inpatient Sample (NIS) database to identify patients with the principal discharge diagnosis of SSS with and without a secondary diagnosis of obesity.

Methods:
Hospitalizations of patients 18 years and older, who had a principal diagnosis of SSS with and without a secondary diagnosis of obesity in the US between January 1, 2016 and December 31, 2017 were obtained from the Nationwide Inpatient Sample (NIS) database for a cohort study. Patient and hospital characteristics are outlined in Table 1. Obese patients were classified according to a BMI>30. Inpatient mortality between non-obese and obese groups was assessed as the primary outcome. Secondary outcomes included total hospital charges (THC), hospital length of stay (LOS), rate of pacemaker insertion, rate of acute renal failure (AKI), and rate of cardiogenic shock.

Results:
Patients with SSS and obesity, in comparison to those without obesity, had similar odds of inpatient mortality (aOR: 1.09, 95% CI 0.66-1.80), p=0.727) when adjusted for co-morbidities. Patients with obesity had higher length of stays (LOS) (4.5 vs 4 days, 0.2 CI: 0.1 - 0.4, p=0.002), higher odds of pacemaker insertion (aOR: 1.14, 95% CI:1.02-1.26, p=0.018), and higher rates of cardioversion/defibrillation (aOR: 1.36, 95% CI: 1.08 - 1.71, p=0.008). Summary of outcomes is outlined in Table 2.

Conclusions:
In conclusion, there was no difference between obese and non-obese patients with SND in regard to inpatient mortality, but obese patients may have higher lengths of stay and increased odds of pacemaker insertion and cardioversion or defibrillation during their hospital stay.
Abstract 8876: Role of Device Temperature Sensor and Impedance in a Rabbit Model of Bacterial Pocket Infection versus Systemic Endotoxemia
Authors: Musley Shailesh Kumar V , Shrivastav Maneesh , Kadrolkar Abhijit , Sharma Vinod
Published: April 2024

Introduction:
Device infections are associated with considerable morbidity, mortality, and cost. The feasibility of temperature sensor performance and impedance measurements in the dual chamber pacemaker was evaluated.

Hypothesis:
An infection can cause local temperature to rise around the implanted device.

Methods:
All rabbits received two subcutaneous pacemaker implants in the thoracic region. The prototype device measured both temperature and local pocket impedance. A control device measured only temperature. After collecting baseline data, rabbits were assigned to either pocket infection (n=6) or systemic infection (n=6) groups. In the pocket infection group, one implant site was inoculated with Staphylococcus aureus suspension (5x106 CFU/mL) and the other control site received saline. In the systemic infection group, each animal received intravenous injections (17.7-35 μg/kg body weight) of E. coli endotoxin for 5 consecutive days. Animals were recovered and monitored for 14 days. The device temperature and pocket impedance data were logged every 10 minutes.

Results:
The temperature measurements increased significantly in all the rabbits, by 15.4 hours after the bacterial inoculation in the pocket. Compared to 24-hour baseline temperature of 38.83±0.04°C, the temperature increased by 2.03°C (40.86±0.25; P=0.005). The mean pocket impedance decreased significantly by 26 Ohms compared to baseline. In the systemic infection animals, significant increases in temperatures (~1.5 °C; P=<0.01) after each endotoxin challenge were observed, compared to baseline.

Conclusions:
These results show that shifts in temperature and impedance can be used to detect pocket or systemic infections. It is feasible that an “infection status” may be determined from longitudinal temperature measurements. Prospective data are needed to demonstrate performance of the temperature algorithm following device implantations.
Abstract 8880: Utility of Telemedicine 3d Transesophageal Echocardiography in Interventional Procedures in Covid-19 Pandemic and Its Impact on Physician Learning
Authors: Le Lisa , Aguilar Jesse , Hill Tracy , Brewer Carlie , Gonzalez de Alba Cesar , Friesen Richard , Frank Benjamin S , Burkett Dale , Jone Pei-ni
Published: April 2024

Background:
Three-dimensional transesophageal echocardiography (3DTEE) is a diagnostic tool in cardiac procedures, but COVID-19 has made utility challenging. Training junior (JR) attendings and fellows in 3DTEE guidance cases in procedural rooms make it tough to maintain adequate social distance. Collaboration Live (CL) is an application on the ultrasound machine that allows for live communication and access to real time images with a remote user. The study aims were to assess the usefulness of CL during 3DTEE guided procedures and its impact on physician learning.

Methods:
3DTEE was obtained in 8 cohorts ranging 4 - 52 years of age on the EPIQ ultrasound machine. CL was used in transcatheter atrial/ventricular septal defect closures, transvenous pacemaker lead placement, and Fontan fenestration closure. 3DTEE was directed by a senior (SR) 3D attending over CL at a remote workstation while a JR attending, cardiac fellow, and echocardiographer performed 3DTEE in the procedural room. A CL post survey was given
.
Wait time from received page to the start of TEE, TEE duration, fluoroscopy time, absorbed X-ray dose, and saved amount of personal protective equipment (PPE) was noted.

Results:
A JR attending was in 8/8 cases. CL decreased reliance on SR attending and improved independence in 86% of cases, and no change in 14%. A fellow was in 6/8 cases. CL decreased reliance on SR 3D attending and increased independence in 67% of cases, and no change in 33%. A SR attending was remotely present in all cases. CL allowed flexibility for SR attending in 89% of cases and no flexibility in 11%. Preferred learning skill, comfort performing/giving results over CL, learning/teaching impact, remote user wait time, reduced radiation exposure, and saved amount of PPE are shown in Table 1.

Conclusions:
CL is valuable in 3DTEE guidance procedures. It increases cost savings by reducing PPE and promotes learner independence. CL allows flexibility and reduces radiation exposure for remote users.
Abstract 8885: Exercise Capacity as a Prognostic Marker in Renal Transplant Cardiovascular Assessment
Authors: Tan Sean , Thang Yi Wen , Mulley William R , Polkinghorne Kevan , Ramkumar Satish , Cheng Kevin , Brown Adam , Moir Stuart , Cameron James D , Marwick Thomas , Nicholls Stephen , Mottram Philip , Nerlekar Nitesh
Published: April 2024

Introduction:
Pharmacological stress testing is routinely performed for cardiovascular assessment in kidney transplant candidates due to perceived poor exercise capacity in such patients. Although exercise stress testing is feasible, the prognostic utility of exercise capacity in this patient population has not been investigated.

Hypothesis:
We hypothesize that exercise capacity predicts long term cardiovascular risk in kidney transplant candidates undergoing exercise stress echocardiography (ESE) for pre-transplant cardiovascular assessment.

Methods:
We prospectively evaluated 898 patients with stage 4/5 chronic kidney disease from 2013 to 2020 who performed symptom limited treadmill ESE. Exercise capacity was calculated as age and sex predicted metabolic equivalents (METs). The primary outcome was incident major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction and stroke. Cox proportional hazard multivariable modelling was performed to identify predictors of MACE, with transplantation treated as a time-varying covariate.

Results:
There were 106 MACE. During follow up, 525 (58%) received a kidney transplant. Achievement of predicted METs (hazard ratio (HR) 0.49, 95% confidence interval (CI) 0.29-0.82, p=0.007) and transplantation (HR 0.52, 95% CI 0.30-0.91, p=0.02) were independently associated with less incident MACE. Patients who achieved predicted METs had similar rates of MACE irrespective of subsequent transplantation (
Figure 1
, HR 0.78, 95% CI 0.32-1.92, p=0.59). Patients who achieved predicted METs and were not transplanted had similar outcomes to those that did not achieve predicted METs and received a kidney transplant (
Figure 1
, HR 0.97, 95% CI 0.42-2.25, p=0.95).

Conclusions:
Exercise capacity is associated with reduced MACE in kidney transplant candidates. Achievement of predicted METs confers excellent prognosis independent of subsequent transplantation.
Abstract 9027: Predictors of Willingness to Change Dietary Patterns in Patients With Atrial Fibrillation
Authors: Strickling Jarred , Mark Erica , Swinehart Sarah , Puthumana Joe , Mehta Nishaki
Published: April 2024

Introduction:
There has been a significant body of international literature supporting the favorable role of diet and lifestyle interventions in improving outcomes in patients with atrial fibrillation (AF). US-based dietary studies are limited. We aimed to study the predictors for patients willing to consider diet changes so target populations can receive increased attention in regards to dietary education.

Methods:
We conducted a pilot telephone survey to discuss willingness to participate in guided dietary intervention in patients with AF at a tertiary care center. If the patients were willing to participate, the process would entail diet counseling via bi-weekly phone calls and monthly surveys to assess dietary compliance. There was no financial incentive offered for their participation. Chart review was done to collect patient characteristics. Zip code was used as a surrogate to determine income level based on census data.

Results:
We attempted to contact 409 patients of whom we were able to reach 162 (39%) patients. 59 patients (36%) were willing to consider diet modification (Group A) while the remainder patients declined (Group B). The average age for both groups was similar (69±8 and 68±9 years respectively). There were 38% and 47% women in groups A and B respectively (p=0.4) There was no difference in the BMI, type of atrial fibrillation, EF, history of hypertension, diabetes, CAD, CKD, anxiety or depression medication use. Social determinants such as marital status, insurance status was similar in both groups. The median income was $57,500 in the study population. The ratio of patients with income over this level was identical in Groups A and B (46 and 52% respectively, p =0.5)There were significantly higher proportion of Caucasian patients in Group A compared to Group B (p=0.02). Patients in Group A were on a lower number of medications compared to Group B (7.3±4 vs 9±4 respectively, p =0.03).

Conclusions:
Patient willingness is generally the first factor for successful implementation of lifestyle modifications. Determining the factors which drive this willingness or pose as barriers to lifestyle modification can assist in formulation of targeted intervention strategies.
Abstract 9032: Restoration of Normal Cardiomyocyte Basal and β-Adrenergic Receptor (AR) Subtype Modulation in Diabetic Cardiomyopathy by Chronic Selective Beta3-AR Antagonist in a Mouse Model of Type 2 Diabetes
Authors: Cao Jing , Sun Xiaoqiang , Cheng Heng , Liu Yixi , Chen Zhe , Zhao David , McClain Donald , Kitzman Dalane W , Cheng Che Ping
Published: April 2024

Background:
We have shown that L-748,337 (L-7), a selective β
3
-adrenergic receptor (AR) antagonist reversed LV dysfunction and β-AR desensitization in diabetes (DM) caused diabetic cardiomyopathy (DCM). The mechanism is unclear. Recent evidence suggests that normal myocardial performance depends on the balance in myocyte β
3
-, β
1
-, and β
2
-AR. Pivotal restructuring of β-AR system resulting in the decline of β-AR reserve plays a crucial role in DCM. We assessed the hypothesis that chronic L-7 would prevent DCM-induced abnormalities of β-AR subtype-stimulated regulation on intrinsic LV myocyte function and [Ca
2+
]
i
regulation, thus restoring cardiac function.

Methods:
Studies were conducted in 3 groups of female mice:
Type 2 DM (T2)
(n=9), induced with high-fat diet (HFD) intake for 14 weeks (W), but after fed HFD for 4 W receiving streptozotocin (STZ, 40 mg/kg/day, i.p. for 5 days);
T2/L-7
(n=7), T2 mice at 10 W received L-7 (10
-7
M/kg/day, mini-pump) for 4 W; and
Controls
(C)(n=9). We compared LV myocyte contractile and [Ca
2+
]
iT
responses to β-AR subtype stimulation by random exposure of myocytes to Isoproterenol (ISO,10
-8
M) or a selective β
1
-, β
2
-, or β
3
-agonist, Norepinephrine (NE, 10
-7
M), Zinterol (ZIN, 10
-5
M) and BRL-37,344 (BRL, 10
-8
M), respectively, during drug perfusion.

Results:
T2 and T2/L-7 mice had mean blood glucose levels of 388 mg/dl and 369 mg/dl, respectively. Versus C, only in T2, basal LV myocyte contractility (dL/dt
max
, 76 vs 133 μm/s), relaxation and [Ca
2+
]
iT
(0.16 vs 0.21) were significantly decreased. ISO-stimulated dL/dt
max
(40% vs 58%) was attenuated accompanied by a diminished NE-mediated increase in dL/dt
max
(28% vs 44%), but enhanced BRL-induced decreases in dL/dt
max
(29% vs 12%).The response of dL/dt
max
(24% vs 15%) to ZIN was increased. Importantly, in T2/L-7 myocytes, the basal dL/dt
max
(128 μm/s) and [Ca
2+
]
iT
(0.21) remained close to control values with preserved β-stimulated positive modulation on cell contraction. The increases in dL/dt
max
in response to ISO (57%), NE (40%) or ZIN (15%) were similar to that in control myocytes, respectively.

Conclusions:
Chronic β
3
-AR antagonist reverses β-AR signaling defects, resensitizing the β-AR subtype system modulation on LV myocytes function, thus playing a salutary role in DCM.
Abstract 9041: Provider Evaluation for Selection of Evidence-Based Therapies to Reduce Cardiovascular Complications in Patients With Type 2 Diabetes Mellitus Study - Primary Results of the PREFER-DM Study
Authors: Sharma Abhinav , Fudim Marat , Greene Stephen J , Van Spall Harriette G , Zieroth Shelley , Verma Subodh , Vaduganathan Muthiah , Pak Jonathan , Lopes Renato D
Published: April 2024

Introduction:
The attributes that health care providers (HCPs) consider in selecting oral antihyperglycemic agents in the treatment of diabetes are not well understood.

Methods:
In the PREFER-DM study, we used conjoint analysis to evaluate the drug attributes preferred by HCPs toward 3 oral antihyperglycemic drugs: empagliflozin 25 mg (SGLT2i), oral semaglutide 14 mg (GLP-1 RA) and sitagliptin 100 mg (DPP-4 inhibitor). HCPs in the US who regularly treat patients with T2DM were sent an online survey via email; those who participated were asked to select from 6 hypothetical, blinded pair-wise drug profile comparisons of different drug benefits and side effects/risk attributes. Attributes in the survey were derived from published trials and FDA labeling data. The relative importance of one attribute relative to another was calculated.

Results:
The PREFER-DM survey was distributed to 12,806 HCPs and 1052 valid surveys were completed (365 [35%] primary care physicians, 350 [33%] endocrinologists, 337 [32%] cardiologists). Risk reduction of cardiovascular death was the most important perceived attribute (z-test
P
<0.05; Figure). Attributes of reduction in heart failure, risk of nausea/vomiting, decreasing progression of renal disease, and weight reduction were considered to have similar importance. The attributes least selected by HCPs were food and medication restriction and A1c lowering (both had similar importance) followed by risk of diabetic ketoacidosis, risk of genital infection, and avoidance of severe hypoglycemia. The relative ordering of attributes remained consistent across specialties (Figure).

Conclusion:
HCPs across specialities prefer oral antihyperglycemic drug attributes associated with CV risk reduction over side effect profile, tolerability, and adverse outcomes. Whether these preferences translate to prescription patterns and patient acceptance of oral antihyperglycemic drugs in clinical settings remains to be investigated.
Abstract 9048: Heart Failure Training Course for Home Health Aides in New York City: A Mixed Methods Pilot Study
Authors: Sterling Madeline R , Cho Jacklyn , Leung Peggy , Ringel joanna , Silva Ariel , Poon Anthony , Toro Oscar , Herring Natasha , Powell Alena K , Goyal Parag , Julia Loughman , Obodai Michael , Safford Monika M
Published: April 2024

Introduction:
Although home health aides (HHAs) often care for adults with heart failure (HF), studies have found that the majority have not received HF training and lack confidence with HF caregiving. To address this, we tested the feasibility, acceptability, and effectiveness of a virtual HF training course for HHAs.

Methods:
We partnered with the Education Fund of the 1199SEIU United Health Care Workers East, the largest healthcare union in the US, which provides training to 55,000 HHAs in NYC. HHAs typically receive in-person training, but due to COVID-19, we conducted this course virtually. The 2-hour course, taught in English and Spanish, utilized case-based learning and motivational interviewing to engage HHAs in interactive discussions on HF signs, symptoms, and HF self-care. HHAs with access to Zoom (via smartphone, computer, or tablet) were eligible. We conducted pre/post surveys and semi-structured interviews. Measures included: a) feasibility (attendance, retention), b) acceptability (modality, technological ease, satisfaction); and c) effectiveness (change in knowledge [Dutch Heart Failure Knowledge Scale, range 0-15] and caregiving self-efficacy [HF Caregiver Self-efficacy Scale, range 0-100]).

Results:
48 HHAs employed by 15 distinct home care agencies enrolled and completed the course; course size ranged from 4-9 participants. The majority were middle-age women (60% Hispanic, 10% non-Hispanic Black). To participate, 59% used a smartphone, 32% a computer, and 10% a tablet. Compared to prior in-person courses, 83% participants reported that the course ran more smoothly and was more convenient; only 7% reported technical problems. Participants and course instructors reported high levels of satisfaction and engagement. Post-course data showed significant and clinically meaningful improvements in HF knowledge (11.21 [1.90] v. 12.21 [1.85]; p = 0.0000) and HF caregiving self-efficacy (75.21 [16.57] v. 82.29 [16.49]; p = 0.0017).

Conclusions:
A virtual HF training course was feasible and acceptable among HHAs and improved their HF knowledge and caregiving confidence. Efforts to scale and disseminate the course may be warranted. Future studies are needed to test the effect of the course among HHAs and their patients.
Abstract 9049: Masking the Bruce Protocol: Surgical Masks Decrease Exercise Duration
Authors: Prince Adam , Giesen Zachary , Andrew Milbridge , Seifer Benjamin J , Gongal Prajesh , Kearing Stephen , Desaulniers Caitlin , Peritz David
Published: April 2024

Introduction:
Exercise stress echocardiography is a critical tool in the workup and assessment of angina, dyspnea, and cardiac disease. Due to the ongoing COVID-19 pandemic, the American Society of Echocardiography recommends that all patients wear surgical facemasks during exercise stress testing.

Hypothesis:
We hypothesized that masks decrease test duration, increase likelihood of test stoppage due to dyspnea, and increase likelihood of abnormal test results.

Methods:
We performed a retrospective chart review of 565 treadmill stress echocardiograms utilizing Bruce protocol between April 2019-July 2019 (without mask) and April 2020-July 2020 (with mask). Chi square and T testing were used for statistical analysis, controlling for age and gender.

Results:
Unmasked patients had a greater mean exercise duration than masked patients (8:12 min vs 7:35 min, p=.02), and were less likely to have dyspnea during the test than masked patients (odds ratio 0.58 [95% CI 0.39, 0.83], p=.003). Unmasked patients were twice as likely to develop chest pain during the test than masked patients (odds ratio 2.0 [95% CI 1.26, 3.22], p=.003). Lastly, unmasked patients were less likely to have an abnormal test result than masked patients, though the difference was not significant (odds ratio 0.81 [95% CI 0.43, 1.51], p=0.50).

Conclusions:
Surgical mask use during treadmill exercise stress tests associated with a significant decrease in test duration, increased dyspnea during the test, and a non-significant increase in likelihood of abnormal test result. Given the critical importance of stress testing in ischemia evaluation, further exploration is warranted to determine whether mask use during stress tests affects downstream testing, diagnoses, and outcomes.
Abstract 9052: Upregulation of Cardiac SERCA 2a is a Key Molecular Mechanism of the Protective Effect on Myocardial Aging in Beta3-Adrenergic Receptor Deficiency Mice
Authors: Cheng Heng , Chen Zhe , Zhou Peng , Cao Jing , Sun Xiaoqiang , Herrington David M , Zhao David , Kitzman Dalane W , Cheng Che Ping
Published: April 2024

Background:
We have shown previously that aging-induced cardiomyocyte dysfunction and impaired β-adrenergic regulation were prevented in β
3
-adrenergic receptor (AR) knockout (β
3
KO) aged mice. However, the molecular mechanism is unclear. We hypothesize that reversal of aging-induced down-regulation of SR Ca
2+
-ATPase (SERCA 2a) and β
1
-ARs by β
3
-AR deficiency may play a key role for the protective effect.

Methods:
We compared cardiac SERCA 2a, phospholamban (PLB), β
1
- and β
3
-AR protein expression and myocyte contractile and [Ca
2+
]
i
transient ([Ca
2+
]
iT
) responses to isoproterenol (ISO, 10
-8
M) in left ventriclar (LV) myocytes obtained from 2 young (Y)(~4-6 mo) and 2 aged (A) (~18-24 mo) groups (7/group) of wild-type (WT) and β
3
KO mice, respectively.

Results:
Compared with YWT, AWT myocytes had significantly decreased SERCA 2a (66%, AWT: 0.21 vs YWT: 0.61), SERCA 2a/PLB ratio (0.76 vs 1.77) and β
1
-AR (33%, 0.39 vs 0.58), but increased β
3
-AR (93%, 0.27 vs 0.14). These changes were associated with reduced basal cell contraction (dL/dt
max
) (AWT: 84.3 vs YWT: 124.8 μm/s), relaxation (dR/dt
max
) (60.1 vs 89.8 μm/s) and [Ca
2+
]
iT
(0.17 vs 0.22). This was accompanied by diminished ISO-stimulated positive inotropic effect; in AWT myocytes, ISO (10
-8
M) caused significantly less increases in dL/dt
max
(AWT: 33% vs YWT: 81%), dR/dt
max
(24% vs 58%), and [Ca
2+
]
iT
(14% vs 34%). Compared with YWT, Yβ
3
KO did not alter basal contraction and ISO response of myocytes, but SERCA 2a (Yβ
3
KO: 1.2 vs YWT: 0.61) and SERCA 2a/PLB ratio were doubled with relatively unchanged β
1
-AR (0.62 vs 0.58); Aβ
3
KO mice had similar alterations. Importantly, in contrast to AWT, in Aβ
3
KO myocytes, the increased SERCA 2a (1.1) and β
1
-AR (0.61) correlated with normal basal cell contraction and relaxation with preserved ISO-stimulated positive inotropic response. ISO caused similar increases in dL/dt
max
(84% vs 82%) and [Ca
2+
]
iT
(32% vs 34%) compared to Yβ
3
KO mice.

Conclusions:
Chronic β
3
-AR deficiency upregulates cardiac SERCA 2a, prevents aging-induced downregulation of β
1
-ARs, and leads to the preservation of myocyte function, [Ca
2+
]
iT
, and β-adrenergic responsiveness in aged hearts. Thus, antagonizing β
3
-AR could be a new therapeutic strategy for age-related decline in myocardial function.
Abstract 9054: Cell-Specific Regulation of the GATA-4/6 Transcription Factors by the Metabolic Enzyme PKM2 Provides Insight into a Biologic Function Essential for Cardiac Health and Survival
Authors: Lorenzana Carrillo Maria Areli , Gopal Keshav , Byrne Nikole J , Saleme Bruno , Das Subhash K , Tejay Saymon , Zhang Yongneng , Haromy Alois S , Eaton Farah , Dyck Jason R , Michelakis Evangelos D , Sutendra Gopinath
Published: April 2024

Background:
Pyruvate Kinase M2 (PKM2) is a glycolytic enzyme that can translocate to the nucleus and regulate different transcription factors (TF). Although its function has been studied extensively in cancer, its biologic role in the heart, and specifically terminally differentiated adult cardiomyocytes (CM), remains elusive.

Hypothesis:
Because PKM1 is the more abundant isoform in CM, we speculated that PKM2 would not have a genetically redundant role to PKM1 and may instead be critical in regulating CM-specific TF.

Methods:
Transverse aortic constriction (TAC) banding model was used to assess the levels and modifications of PKM2 during heart failure (HF). CM-specific PKM2-deficient mice were generated to evaluate the biological role of PKM2 in adult CM. Unbiased RNA sequencing was utilized to assess novel PKM2-induced signaling pathways in adult CM. Induced pluripotent stem cells (iPSCs) were used to translate mechanistic findings to mature human CM.

Results:
PKM2 levels were lower, but serine-37 phosphorylated PKM2 (
S37
P-PKM2) was higher in terminally differentiated tissues. Cell-specific analysis showed
S37
P-PKM2 was preferentially localized in the nucleus of CM, compared to cardiac fibroblasts (CF) (where PKM2 was mainly cytoplasmic). During TAC-induced HF, PKM2 levels increased in CF but correspondingly decreased in CM, in comparison to sham controls. CM-specific PKM2-deficient mice developed age-dependent cardiac dysfunction with decreased survival, compared to their control littermates. Unbiased RNA sequencing revealed a decrease in cardiac energetic, stress response, angiogenesis, repair and regeneration, and survival pathways from PKM2-deficient CM. In keeping, PKM2-deficient hearts had decreased levels of the cardiomyocyte-specific TF GATA4 and GATA6, compared to control hearts. Finally, the E3 ubiquitin-ligase TRIM35, which was induced during TAC-induced heart failure, ubiquitinated and degraded PKM2, along with GATA4 and GATA6 in primary adult mouse or human iPSC-derived CM.

Conclusions:
This study shows a new and previously unrecognized role for PKM2 in the regulation of cardiomyocyte-specific transcription factors and identifies a novel therapeutic target (TRIM35) in heart failure.
Abstract 9070: Use of Commercial Outpatient Monitoring for Near-Real-Time, Acute- and Subacute-Care Telemetry Like Monitoring in Covid-19 Pandemic
Authors: Tan Jian , Krathen Jonathan , Hunter Krystal , Andriulli John A , Ortman Matthew , Russo Andrea M
Published: April 2024

Introduction:
Limited data exist on the role of commercial mobile cardiac telemetry (MCT) monitoring with QT capability as a near-real-time inpatient monitoring tool for COVID-19 stable patients. Our aim was to determine whether outpatient MCT monitoring could be adapted for near-real-time inpatient arrhythmia and QT monitoring during the COVID-19 pandemic.

Methods:
We conducted a prospective observational study on patients ≥18 years old with confirmed COVID-19 who required hospitalization between June and December 2020. Data including baseline characteristics and laboratory data were collected. Cardiac rhythms monitored using the MCT monitors (Medilynx Pocket ECG) were analyzed (beat-to-beat analysis). Off-site technicians monitored for arrhythmias 24/7 and notified the physician based on the pre-defined events (QTc ≥500 ms with QRS <120 ms or QTc >520 ms with QRS ≥120 ms or atrial and/or ventricular tachyarrhythmia ≥5 beats). Primary endpoint was the detection of any of the pre-defined events.

Results:
29 patients were enrolled in this study. 65.5% were female. There were no significant differences except age in baseline characteristics and laboratory data between those with and without events. Patient age was a significant predictor of events at multivariable analysis [odds ratio 1.08, 95% CI (1.01 - 1.15); P = 0.023]. Table 1 showed the overall number and events recorded on the MCT monitors. Two patients had new-onset atrial fibrillation (AF) and 5 patients had AF with heart rate >100 bpm. In retrospective analysis, these findings correlated with the 12-lead ECGs performed during their hospital stays. Two patient had significant QTc prolongation noted on the MCT monitor. No adverse events occurred in any of the monitored patients.

Conclusions:
Our results showed that commercial MCT monitoring can potentially provide a system for detecting clinically relevant arrhythmias and QT prolongation, especially if there is a subsequent shortage of telemetry monitors.
Abstract 9071: Prognosis of Elderly Non-Valvular Atrial Fibrillation Patients Stratified by B-type Natriuretic Peptide Concentration: A Subanalysis of Data from the ELDERCARE-AF Trial
Authors: Okazaki Osamu , Higashino Yorihiko , Yokoya Koichi , An Yoshimori , Tanizawa Kimihiko , Imamura Yuki , Hayashi Takuya , Akao Masaharu , Okumura Ken , Yamashita Takeshi
Published: April 2024

Introduction:
B-type natriuretic peptide (BNP) is a known predictor of prognosis and disease severity in patients with heart failure. However, only limited data are available on the relation between BNP and outcomes in very elderly (age, ≥ 80 years) patients ineligible for standard anticoagulation with non-valvular atrial fibrillation (NVAF). Therefore we evaluated the prognostic and therapeutic outcomes of very elderly Japanese NVAF patients stratified by BNP concentration.

Methods:
This was a subanalysis of data from ELDERCARE-AF, a multicenter, randomized, double-blind, placebo-controlled phase 3 study of edoxaban 15 mg (once daily) in very elderly Japanese NVAF patients considered ineligible for standard anticoagulant treatment. Patients were stratified according to BNP concentration at enrollment, and their outcomes were compared. The primary efficacy endpoint was stroke or systemic embolism (SSE). The primary safety endpoint was major bleeding.

Results:
A total of 984 patients (mean age, 86.6 years) were randomized to edoxaban 15mg (
n
= 492) or placebo (
n
= 492). BNP concentration at enrollment was < 200 pg/mL (low), 200 to < 400 pg/mL (moderate), and ≥ 400 pg/mL (high) in 428, 300, and 256 patients, respectively. Mean CHADS
2
score was 2.9 in the low BNP and 3.2 in the moderate and high BNP groups. The incidences of SSE were 1.2%/patient-year (7/428), 5.9%/patient-year (24/300), and 8.6%/patient-year (28/256) in the low, moderate, and high BNP groups, respectively: unadjusted HR = 5.03 (95% confidential interval [CI], 2.17-11.67),
P
= 0.0002, for low versus moderate BNP; unadjusted HR = 7.07 (3.09-16.18),
P
< 0.0001, for low versus high BNP. No significant intergroup differences were found for the incidence of major bleeding. Edoxaban 15mg was superior to placebo in preventing SSE in the moderate and high BNP groups: unadjusted HR, 0.27 (0.10-0.73),
P
< 0.01, and unadjusted HR, 0.34 (0.15-0.81),
P
< 0.05, respectively. There was no significant difference in major bleeding between the edoxaban 15mg and placebo groups.

Conclusions:
In very elderly NVAF patients, BNP concentration was positively related to the incidence of SSE, and edoxaban 15mg had a preventive effect, regardless of BNP concentration.
Abstract 9075: Long-Term Prognostic Value of Cardiac MIBG Imaging and 6-Minute Walk Distance for Ventricular Tachyarrhythmias in Patients With Implantable Cardioverter Defibrillator
Authors: Kawasaki Masato , Yamada Takahisa , Watanabe Tetsuya , Morita Takashi , Kikuchi Atsushi , Kawai Tsutomu , Seo Masahiro , Nakamura Jun , Kayama Kiyomi , Ueda Kunpei , Sakamoto Daisuke , Kogame Takehiro , Tamura Yuto , Fujita Takeshi , Nishigaki Keisuke , Kokubu Yuki , Fukuda Yuto , Fukunami Masatake
Published: April 2024

Backgrounds:
Cardiac MIBG imaging provides prognostic information in patients with chronic heart failure (CHF). Recent studies showed that the highest occurrence of severe arrhythmic events (SAE) was seen in CHF patients with an intermediate decrease in MIBG uptake rather than the lowest values. On the other hand, 6-minute walk distance (6MWD) has been shown to be associated with poor prognostic outcome in CHF patients. However, there is little information available on long-term prognostic value of intermediate decrease in MIBG uptake and 6MWD for the prediction of ventricular tachyarrhythmias in implantable cardioverter defibrillator (ICD) patients.

Methods and Results:
We prospectively enrolled 232 consecutive outpatients with ICD (age: 65±14 years, male: 81%, NYHA class: 1.7±0.7, LVEF: 47±17%). At entry, all patients underwent cardiac MIBG imaging and 6-minute walk test. An intermediate decrease in heart-to-mediastinum ratio on delayed planar image (H/M) was defined as 1.40-1.89. During a follow-up period of 4.4±2.8 years, 73 patients had appropriate ICD discharge for ventricular tachyarrhythmias. At multivariate Cox analysis, intermediate decrease in H/M and 6MWD were significantly and independently associated with appropriate ICD discharge after adjustment for age, sex, NYHA class and LVEF. Appropriate ICD discharge was significantly more frequently observed in patients with both intermediate decrease in H/M and shorter 6MWD (≤300m) and with either intermediate decrease in H/M or shorter 6MWD than with none of them (49 % vs 35% vs 18%, p<0.0001).

Conclusion:
Combination of cardiac MIBG imaging and 6MWD would be more strongly associated with an increased risk for ventricular tachyarrhythmias in ICD patients.
Abstract 9083: Beta1-Adrenergic cAMP Signaling is Uncoupled after Acute Treatment of Anthrax Lethal Toxin in Cardiomyocytes in Normal Rats
Authors: Sun Xiaoqiang , Cheng Che Ping , Cao Jing , Chen Zhe , Zhang Xiaowei , Liu Yixi , Callahan Michael , Cheng Heng
Published: April 2024

Background:
Our recent
in vivo
study has shown that anthrax lethal toxin (LeTx) causes time-dependent progressive depression of left ventricular (LV) contractility and β-adrenergic reserve. However, the mechanisms are poorly understood. We tested the hypothesis that LeTx-induced altered cardiac subtypes of β-adrenergic receptor (AR) regulation may contribute to this effect.

Methods:
We examined acute exposure of LeTx caused alterations of myocyte β
1
- and β
3
-AR expression and myocyte basal contraction and relaxation and responses to isoproterenol (ISO), a β-AR agonist, and colforsin (COLF), a cAMP activator. Cardiomyocytes were isolated from eight adult normal rats incubated for 6 hours in study buffer without and with LeTx (10 nM PA and 1 nM LF).

Result:
Compared with controls, LeTx treatment caused no significant changes on basal myocyte contraction and relaxation. Myocyte β
1
-AR (0.47±0.04 vs 0.46±0.02) and β
3
-AR (0.21±0.02 vs 0.23±0.02) protein levels also remained relatively unchanged. In controls, superfusion with ISO (10
-8
M) caused about 46% increase in cell percent shortening (SA, 14.5 vs 10.0%) and 83% and 44% increases in peak velocity shortening (dL/dt
max
, 270.0 vs 147.7 μm/s) and relengthening (dR/dt
max
, 172.2 vs 119.6 μm/s), respectively. However, after LeTx treatment, myocyte positive inotropic functional response to β-AR stimulation was significantly decreased. In LeTx-treated myocytes, ISO produced significantly less increases in SA (25%, 9.9 vs 12.3%), dL/dt
max
(29%, 130.5 vs 183.6 μm/s) and dR/dt
max
(32.4%, 87.5 vs 115.8 μm/s). In contrast, superfusion of COLF (10
-6
M) caused similar increases in SA (43.1 vs 43.7%), dL/dt
max
(77.4 vs 83.2%) and dR/dt
max
(35.2 vs 30.8%). In addition, compared with normal controls, LeTx-treated myocyte contractile responses to zinterol (ZIN, 10
-5
M), a highly selective β
2
-AR agonist, and BRL-37,344 (BRL, 10
-8
M), a selective β
3
-AR agonist, were also unaffected.

Conclusion:
Acute treatment of LeTx causes cardiac myocyte β
1
-AR uncoupling from cAMP-mediated signaling and impairs myocyte β-adrenergic reserve. These results suggest that the early changes in cardiac subtypes of β-AR signal transduction system may mediate the connection between the acute and chronic cardiac action of LeTx.
Abstract 9092: Association of Biomarkers of Oxidative Stress, Inflammation, and Cardiac Damage with Long-Term Radiation-Induced Cardiovascular Outcomes in Breast Cancer
Authors: Vasbinder Alexi , Heckbert Susan R , Cheng Richard , Thompson Hilaire J , Zaslavsky Oleg , Chlebowski Rowan , Johnson Lisa , Yung Rachel , Wactawski-Wende Jean , Shadyab Aladdin H , Wells Gretchen , Warsinger Martin Lisa , paskett electra , Reding Kerryn
Published: April 2024

Introduction:
Radiation therapy (RT) is a common component of breast cancer (BC) management, but may be associated with radiation-induced cardiovascular disease (RICVD) which includes coronary heart disease, myocardial infarction, CVD death, heart failure, or stroke. We examined associations of biomarkers of oxidative stress (MPO, GDF-15, 8-OH-dG, PGF), cardiac injury (TnI, Cystatin-C), inflammation (IL-6, CRP), and myocardial fibrosis (TGF-B) with long-term RICVD in BC survivors.

Methods:
In an ancillary, nested case-control study within the Women’s Health Initiative, postmenopausal women with incident BC stages I-III, who received RT, and had pre- and post-BC diagnosis serum samples available not more than 3 years apart were eligible. Cases were defined as developing incident, physician-adjudicated coronary heart disease, myocardial infarction, CVD death, heart failure, or stroke after BC. Each case was matched to 3 controls on enrollment age and visit year of pre-BC blood draw. Biomarkers were analyzed using enzyme-linked immunosorbent assays and modeled as the post-BC to pre-BC ratio and log transformed to base 2. Logistic regression models were adjusted for demographic, lifestyle, and cancer characteristics.

Results:
A total of 55 cases and 158 controls were included with a mean (SD) age of 66.9 (5.5) years and a median (IQR) time from BC diagnosis to post-BC serum collection of 1.4 (0.7, 2.4) years. After adjustment, a higher 8-OH-dG ratio was significantly associated with an elevated risk of RICVD (Table). For a doubling in the biomarker ratio, RICVD risk was 3.04-fold higher (95% CI: 1.01, 9.21). Other biomarkers were not associated with RICVD risk.

Conclusions:
In this study, higher concentrations of 8-OH-dG were associated with a higher risk of RICVD. This suggests that oxidative DNA damage may be a putative pathway for delayed RICVD. However, given the sample size and multiple testing, further studies are needed to confirm or refute these findings.
Abstract 9096: Young Adults With Early-Onset Cardiovascular Risk Factors Demonstrate Subclinical Alterations in Cardiac Morphology and Function
Authors: Snel Gert , van den Boomen Maaike , Slart Riemer , Nguyen Christopher , Sosnovik David , van Deursen Vincent , Dierckx Rudi , Velthuis Birgitta , Borra Ronald , Prakken Niek
Published: April 2024

Background:
Overweight, hypertension and type 2 diabetes (risk factors) are associated with subclinical alterations in cardiac morphology and function in asymptomatic mature adults (age >40 years). However, the time and extent of these cardiac alterations is unknown in the young adult (age 21-40 years) population with increasing early-onset risk factors, possibly overlapping findings in cardiomyopathy.

Hypothesis:
Risk factors already cause subclinical cardiac alterations in asymptomatic young adults.

Methods:
Non-smoking nonathletic adults aged 21-40 years without cardiac history underwent MRI for assessment of cardiac morphology and function. Multivariate linear regression analysis was performed to investigate the independent association of risk factor related parameters with cardiac outcomes.

Results:
In total, 279 subjects (49% male, mean age 31±6 years) were included. After adjustment for age, gender and height, all risk factors had significant impact on cardiac outcomes (Table+Figure). Most importantly, higher body mass index was associated with increases in left ventricular (LV) mass (ß=1.30), end-diastolic volumes (EDV) (LV, ß=1.82) and stroke volume (ß=1.04). Further, systolic blood pressure was positively associated with LV mass (ß=0.52), mass-volume ratio (ß=0.0024), stroke volume (ß=0.26) and LV ejection fraction (ß=0.073), and HbA1c with LV mass (ß=0.30) and right ventricular EDV (ß=0.43).

Conclusions:
In aysmptomatic young adults without cardiovascular disease, risk factors are associated with subclinical cardiac alterations. These alterations should be considered when evaluating clinical scans in young adults to avoid misdiagnosis.
Abstract 9121: Lipoprotein(a) and the Risk for Coronary Heart Disease and Ischemic Stroke Events Among Black and White Adults with Cardiovascular Disease
Authors: Colantonio Lisandro D , Bittner Vera A , Safford Monika M , Marcovina Santica M , Brown Todd M , Jackson Elizabeth A , Li Mei , Lopez J. Antonio G , Monda Keri L , Plante Tim B , Kent Shia , Muntner Paul , Rosenson Robert S
Published: April 2024

Introduction:
Lp(a) is a risk marker for incident coronary heart disease (CHD) and ischemic stroke. It is unclear if Lp(a) is associated with CHD and stroke events among adults with prevalent cardiovascular disease (CVD), particularly in non-White populations.

Hypothesis:
Higher Lp(a) levels are associated with an increased risk for both CHD and ischemic stroke events in Black and White adults with prevalent CVD.

Methods:
We conducted a case-cohort analysis including Black and White adults ≥45 years of age enrolled in the nationwide REasons for Geographic and Racial Differences in Stroke (REGARDS) study between 2003 and 2007 who had prevalent CVD at baseline. REGARDS study participants were followed for CHD and ischemic stroke events, which were expert adjudicated. Lp(a) molar concentration was measured using a particle-enhanced turbidimetric immunoassay from blood samples collected at baseline in a random subcohort of participants with prevalent CVD (n=1,948), and in all those with prevalent CVD who experienced a CHD event by December 31, 2017 (n=1,166), or an ischemic stroke by September 30, 2019 (n=492).

Results:
The median [25
th
, 75
th
percentile] Lp(a) concentration was 100 nmol/L [48, 186] among Black participants and 23 nmol/L [8, 113] among White participants (p-value <0.001). Higher Lp(a) was associated with an increased risk for CHD events among both Black and White participants, but it was not associated with the risk for ischemic stroke (Table). At baseline, 49% of Black participants and 59% of White participants with prevalent CVD were taking a statin. Among Black and White participants taking a statin, the hazard ratio [95% CI] associated with 1 SD higher log-Lp(a) was 1.69 [0.98, 2.93] and 1.38 [1.03, 1.85], respectively, for CHD, and 1.29 [0.70, 2.40] and 1.18 [0.81, 1.72], respectively, for stroke.

Conclusion:
Higher Lp(a) is a risk marker for CHD but not for ischemic stroke events in Black and White adults with prevalent CVD, including those taking a statin.