bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 8947: A Meta-Analysis of Cardiovascular Outcomes in Clinical Trials of Dapagliflozin
Authors: Langkilde Anna Maria , Sugg Jennifer , Johannson Peter , Ying Lisa , List James , Parikh Shamik
Published: April 2024

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular (CV) disease. Dapagliflozin (DAPA), a selective SGLT2 inhibitor, is currently under evaluation for the treatment of T2DM. DAPA reduces hyperglycemia by promoting renal glucose excretion, independent of insulin secretion or action, also reducing weight and blood pressure. In response to FDA recommendations for new T2DM therapies, a pre-specified meta-analysis was conducted of data from 14 phase 2/3 studies (n=6228) to assess the CV safety of all DAPA doses (2.5 to >10mg/d) pooled (n=4287), relative to all comparators (active or placebo) pooled (n=1941). CV events were systematically identified from investigator reports of adverse events and adjudicated by an independent committee. Adjudication was blinded to treatment allocation and conducted prospectively for the majority of trials. The primary end point was a composite of time to first event of CV death, myocardial infarction (MI), stroke, or hospitalization for unstable angina. The secondary end point included the primary end point, unplanned coronary revascularization, and hospitalization for heart failure. Baseline characteristics were balanced between groups: mean age=56 years, body mass index=31.5 kg/m
2
, and T2DM duration=6 years. Characteristics mirrored CV risk in the general T2DM population and included hypertension (62%), dyslipidemia (49%), smoking history (40%), and CV disease history (19%). A total of 78 primary end point events were confirmed with a stratified event rate (subjects with events/1000 subject years) of 11.3 for DAPA vs 16.6 for comparators. The estimated hazard ratio (HR) using a Cox proportional hazards method was 0.674 (98% CI: 0.385, 1.178; 95% CI: 0.421, 1.078). Analyses of the secondary end point (HR: 0.632; 95% CI: 0.416, 0.959) and of a composite CV death, MI, and stroke end point (HR: 0.596; 95% CI: 0.357, 0.996) were consistent with primary results. Analyses by dose (DAPA 2.5, 5 and 10 mg) were comparable to overall results. Review of data from the 4-month safety update confirmed the conclusions from the initial pre-specified analysis. The results suggest that DAPA is not associated with an increase in CV risk, and are consistent with a potential reduction in CV risk.
Abstract 8949: Intermittent Systolic Overload induces Rapid Ventricular Hypertrophy and Promotes Better Ventricular Function in Young Goats
Authors: Favaro Gustavo A , Assad Renato S , Abduch Maria C , Justo Gustavo , Gomes Guilherme , Andrade José L , Krieger José E , Stolf Noedir A
Published: April 2024

Introduction:
Anatomical repair of transposition of the great vessels beyond the neonatal period requires preparation of the left ventricle for the 2-stage Jatene operation. Previous studies have demonstrated myocardial edema and necrosis in hearts that experience abrupt systolic overload, followed by late ventricular failure.

Hypothesis:
Subpulmonary ventricle retraining with intermittent systolic overload could minimize the inadequacy of conventional pulmonary artery banding and promote better LV function under pharmacologic stress testing.

Methods:
Nineteen young goats were divided into 3 groups: Sham (n=7; no systolic pressure overload), Continuous (n=6; systolic overload maintained for 96 hours) and Intermittent (n=6; 4 periods of 12-hour systolic overload, paired with a 12-hour resting period). Echocardiographic and hemodynamic evaluations were performed every day. Myocardial performance index and ejection fraction were evaluated at rest and during dobutamine stress. The animals were then killed for morphologic evaluation.

Results:
Systolic overload area of Intermittent group, measured by RV to PA pressure gradient over time, was significantly smaller than Continuous group (p<0.05). Nevertheless, both groups had increased RV and septal masses, as compared to Sham (p<0.0002). Echocardiography revealed a major increase in the RV wall thickness of the Intermittent group (+64.8% ± 23.37%), when compared to Continuous group (+43.9% ± 19.26%; p=0.015). RV dilation and dysfunction was observed in both study groups after starting systolic overload (p<0.002). However, only Continuous group remained with significant RV dilation throughout the protocol (p <0.006). Intermittent group presented a significantly better myocardial performance index at the end of protocol, under resting and dobutamine infusion, when compared to Continuous group (p<0.012).

Conclusions:
Both systolic overload protocols have induced a rapid RV hypertrophy. However, only Intermittent group had a better preservation of RV function, at the end of the protocol, both at rest and under dobutamine infusion. This study suggests that intermittent systolic overload may favorably affect the results for 2-stage Jatene operation.
Abstract 8965: C1q/TNF-Related Protein-3, a Newly Identified Adipokine, is a Novel Anti-Apoptotic, Pro-Angiogenic, and Cardioprotective Molecule in the Ischemic Mouse Heart
Authors: Sun Yang , Yi Wei , Lau Wayne Bond , Yuan Yuexing , Zheng Qijun , Wang Xiaoliang , Wang Yajing , Shang Xiying , Gao Erhe , Koch Walter J , Ma Xin-Liang
Published: April 2024

Obesity/diabetes adversely affects ischemic heart remodeling via incompletely understood mechanisms. Adipocytes produce various adipokines. Delineating these adipokines’ cardiovascular profiles is critical in advancing our knowledge regarding how obesity/diabetes may cause cardiovascular damage. C1q/TNF-related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation. However, the cardiovascular actions of this novel adipokine remain unknown. The current study determined whether CTRP3 may regulate post-ischemic cardiac remodeling and cardiac dysfunction, and, if so, sought to elucidate the involved underlying mechanisms. Male adult mice were subjected to MI, and treated with saline or CTRP3 via peritoneally implanted osmotic-pumps for 2 weeks. Plasma CTRP3 levels were significantly reduced 4 hours after MI, and remained at low level until 1 week after MI. Supplementation of CTRP3 (beginning 4 hours after MI) at a dose (0.25 μg/g/day) restoring physiological CTRP3 levels in MI animals improved survival rate (P<0.05), rescued cardiac function (determined by echocardiograph and left ventricular catheterization, P<0.01), attenuated cardiomyocyte apoptosis within infarct border zones (determined by TUNEL staining and caspase 3 activation, P<0.01), increased revascularization (evidenced by CD31 and α-SMA immunostaining, P<0.01), and dramatically reduced interstitial fibrosis (41% reduction vs. vehicle group, P<0.01). In vivo CTRP3 administration had no significant effect upon AMPK phosphorylation, but significantly increased Akt phosphorylation, and increased HIF-1α and VEGF expression. Surprisingly, treatment of HUVECs in vitro with CTRP3 failed to increase tube formation. However, pre-conditioned medium from CTRP3-treated cardiomyocytes significantly enhanced HUVEC tube formation, an effect that was blocked by either pre-treatment of cardiomyocytes with a PI3K inhibitor, or pre-treatment of HUVECs with a VEGF inhibitor. Our results demonstrate for the first time that CTRP3 is a novel anti-apoptotic, pro-angiogenic, and cardioprotective adipokine in the ischemic mouse heart, via facilitation of cardiomyocyte-endothelium communication.
Abstract 8969: Female Sex Is Associated With Increased Mortality After Pediatric Cardiac Surgery
Authors: Kochilas Lazaros , Vinocur Jeffrey , Menck Jeremiah , St. Louis James
Published: April 2024

Surgical mortality for congenital heart defects is affected by several center and patient specific factors. The role of patient's sex as risk factor for death after pediatric cardiac surgery is disputed. We used 1982-2007 outcome data from the Pediatric Cardiac Care Consortium, a large multi-center clinical database to examine whether sex represents a prognostic factor for mortality after pediatric cardiac surgery. Hierarchical multivariate logistic regression analysis was used to determine the odds ratio (OR) of death for females vs. males after cardiac surgery in children (<18 years old) adjusting for RACHS-1 risk category, patient's age and weight at operation (neonates and infants < 2.5 kg, neonates > 2.5 kg, infants > 2.5 kg, children 1-5y, 6-12y, 13-18y), and 5-year time period of operation. Kaplan-Meier survival curves were generated to examine survival between females and males. After excluding cases without defined risk category or from years with incomplete data, 70,595 patients with 85,023 operations (53.9% males) were included in the analysis. The unadjusted OR for death between females and males was not statistically significant (OR 0.98, 95% CI 0.92-1.04). Males were more likely than females to have cardiac surgery of higher severity and as a neonate, both associated with higher risk of postsurgical mortality. After adjustment, female sex was associated with higher odds ratio (OR) of postoperative death (OR 1.18; 95% CI: 1.11-1.26, p<0.0001). The sex effect was restricted to neonates (OR 1.29, 95% CI 1.15-1.45, p<0.0001) and adolescents (OR 1.6, 95% CI 1.04-2.47, p=0.0342), and to more complex operations (risk categories 4-6 vs. 1-3 OR 1.28, 95% CI 1.14-1.43, p<0.0001). Kaplan-Meier survival curves after surgery demonstrated that the major separation between the survival curves occurs within one day of the operation and the survival curves are approximately parallel after the first day.

Conclusions:
Female sex is associated with increased risk of early mortality after pediatric cardiac surgery. The risk is age- and risk category-specific affecting mostly neonates and adolescents undergoing higher risk procedures likely to require prolonged exposure to cardiopulmonary bypass.
Abstract 9110: Does Change in Cardiometabolic Risk Factors Relate to Change in Coronary Artery Calcification? Findings from the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Arguelles William , Llabre Maria M , Penedo Frank J , Daviglus Martha L , Sacco Ralph L , Liu Kiang , Szklo Moyses , Polak Joseph F , Eng John , Burke Gregory L , Schneiderman Neil
Published: April 2024

How CVD risk factors impact coronary artery calcification (CAC) remains unclear. Particularly lacking are data describing how change in various risk factor levels relate to change in CAC, which may lead to a greater understanding of these relationships and further inform optimal strategies for CVD prevention and treatment. With data from a multi-ethnic cohort of 4,560 individuals (46.8% men; age M = 61.35) initially free of clinical CVD, this study used latent growth modeling to examine change in specific cardiometabolic risk factors (CRFs; waist circumference, BMI, SBP, DBP, HDL and LDL cholesterol, triglycerides, and fasting glucose) related to change in CAC over an average 4.9 year time period. Data were adjusted for baseline CRF and CAC values, age, race/ethnicity, smoking, family history of CVD, income, and use of antihypertensive, lipid-lowering, and glucose-lowering medications. Men and women were analyzed separately given previously noted differences in clinical CVD development and predictive utility of CRFs. Change in CRFs was not associated with incident CAC among men and women who had undetectable CAC at baseline, or with CAC progression among men who had detectable CAC at baseline. Among women who had detectable CAC at baseline (M = 180.5, SD = 32.4 Agatston units), greater decline (or less progression) in SBP (B = -3.17, p < .05) and DBP (B = -8.56, p < .05), and LDL cholesterol (B = -2.49, p < .05), were each individually associated with greater CAC progression. The associations between change in blood pressure and CAC progression were not independent of change in LDL cholesterol. Medication use appeared to influence these inverse associations, such that women taking antihypertensive and lipid-lowering medications exhibited greater CAC progression despite showing average decreases in respective CRF levels over time. Women not taking such medications did not show these inverse associations. To our knowledge, this is the first study systematically reporting on rates of change in various CRFs related to CAC incidence and progression. Observed inverse associations appear to have been driven by women receiving medications that lowered their initially high risk factor levels but not their increased rate of CAC progression.
Abstract 9111: The Summation of ST-Segment Elevation is a Novel Predictor for Complications in Patients with Stress (Takotsubo) Cardiomyopathy
Authors: Takashio Seiji , Yamamuro Megumi , Kojima Sunao , Tsunoda Ryusuke , Nakao Koichi , Ogawa Hisao
Published: April 2024

Background:
Although the prognosis of stress (Takotsubo) cardiomyopathy (SC) is relatively favorable, it sometimes leads to serious complications. It is generally accepted that electrocardiogram (ECG) highly suggestive of the characteristics of myocardial damage is essential tool for diagnosis of SC. We assessed the hypothesis that serial change and quantitative analysis of ECG are associated with following adverse events in patients with SC.

Methods and Results:
The study patients consisted of 85 patients with SC. A total of 34 patients suffered from 1 or more in-hospital adverse events such as heart failure, intraventricular pressure gradient (>30 mmHg), cardiogenic shock, ventricular tachycardia/fibrillation, and cerebral embolism. Of them, 2 patients died of cardiogenic shock. Patients with adverse events had higher heart rate (96±25 vs. 76±17 bpm, p<0.001) and greater summation of ST-segment elevation in 12 leads (ΣSTE) (10.5 [5.0 to 17.5] mm vs. 3.0 [0 to 7.0] mm; p<0.001) than those with non-adverse event. A multivariate logistic regression analysis showed that heart rate and ΣSTE were independent predictive variables (Table) and the best cutoff level of ΣSTE for prediction of adverse events was 5.5 mm based on a receiver operating characteristic curve. The ST-segment elevation in adverse events group extended up to limb leads as well as precordial leads compared with that in non-adverse evnets group (50% vs. 12%; p<0.001). However, a significant difference was not observed regarding ST resolution <50% at 24 hour after hospital admission clinically suggestive of prognostic impairment of SC between 2 groups (38% vs. 43%; p=0.80).

Conclusions:
Electrocardiographic extent and magnitude of ST-segment elevation can predict in-hospital adverse events following SC. Our findings may help to explain the missing link between ECG changes and the severity of catecholamine-induced myocardial damage deeply involved in fatal and non-fatal complications.
Abstract 9116: In Patients with Preserved Ejection Fraction, Newer Measures of Systolic Function Have Better Correlation with Functional Status Than Do Traditional Measures of Diastolic Function
Authors: Nazir Talha F , Petersen John W
Published: April 2024

Introduction:
Multiple abnormalities in left ventricular (LV) systolic and diastolic function have been demonstrated in patients with heart failure and preserved ejection fraction. We aimed to determine which echocardiographic measures of LV systolic or diastolic function best correlate with functional status in patients with preserved ejection fraction (EF).

Methods:
Patients referred for clinically indicated echos who had images adequate for evaluation of regional myocardial function were approached for enrollment. Functional status was determined by the Duke Activity Status Index (DASI), which correlates with peak oxygen uptake. Echos were analyzed by investigators blinded to DASI scores. EF was determined with Simpson's biplane method. Speckle tracking echo (STE) (QLab version 7.1 Philips, The Netherlands) was used to determine peak circumferential, radial, and longitudinal strain for each LV segment. Torsion was defined as the maximal difference between apical and basal twist. Standard Doppler techniques were used to measure peak early (E) and atrial (A) filling velocities as well as peak early velocity (E') of the medial mitral annulus.

Results:
34 patients with an EF ≥ 45% were enrolled. There was no correlation between E/E' and DASI scores (r=0.008, p=0.97, n=24). Whereas, there was a relatively strong correlation between DASI scores and radial strain (r=0.703, p=0.003, n=15). There were moderate correlations between DASI scores and global longitudinal strain (r=-0.54, p=0.038, n=15), global circumferential strain (r=-0.392, p=0.087, n=20) and torsion (r=0.462, p=0.054, n=18). Using a backwards fit technique, a model including global radial strain and torsion provides the best prediction of DASI scores, [DASI score = -9.039 + (2.141×torion) + (1.083× radial strain)], (r= 0.731, p=0.003 n=14).

Conclusions:
In our cohort of patients with preserved EF, traditional measures of diastolic function (E/E') had no correlation with functional status. Systolic measures, such as radial strain, correlated the best with functional status. STE derived measures of LV systolic events may be a more appropriate variable than traditional diastolic measures in studies investigating patients with preserved EF.
Abstract 9123: Utilization of TIMI Risk Index in Determining the Need of Admission to Coronary Care Unit for Acute ST Elevation Myocardial Infarction Patient After Successful Primary Percutaneous Coronary Intervention: Single Centre Study
Authors: Tan Vern Hsen , Tan Chong Hiok , Chow Jeremy , Tan Kok Soon , Lingamanaicker Jayaram , Lim Victor , Tong Khim Leng , Leong Gerard , Gan Hwa Wooi , Ong Sea Hing , Goh Yew Seong , Yeo Colin , Goh Ping Ping
Published: April 2024

Introduction:
With the ever-increasing number of acutely ill patients with cardiac disease that need intensive monitoring and limited resources in coronary care unit (CCU), there is a need to ensure appropriate admission to CCU. TIMI risk index (TRI) was a robust predictor (for STEMI patients on first arrival in hospital) and high discriminatory capacity of in-hospital events. TRI was divided into five risk groups with the higher the index score, the higher the mortality. We attempt to study TIMI risk index {TRI = [heart rate X (age/10)2]/systolic blood pressure} in determining the need of admission to CCU for STEMI patient after successful primary percutaneous coronary intervention (PPCI).

Methods:
This was a retrospective study over 12 months period. Inclusion criterias including patient presented with STEMI at emergency department and underwent successful PPCI which defined as achieving TIMI 3 flow. Exclusion criterias include no documentation of blood pressure and/or heart rate at presentation at emergency department. Study end point was in-hospital major adverse cardiovascular events (MACE) that include all cause death including cardiac death, target lesion revascularization, recurrent myocardial infarction, stroke, in-stent thrombosis.

Results:
A total of 275 patients had STEMI and underwent PPCI. 16 patients were excluded (13 patients did not have heart rate and/or blood pressure documented at presentation and 3 patients had unsuccessful PPCI). Majority was male (85.3%) and had anterior STEMI (51.0%). In the first two groups (risk group 1 and risk group 2), there was no in-hospital MACE as compare to the last two groups (risk group 4 and risk group 5), in which the in-hospital MACE was >10% (12.2% and 17.0% respectively, p=0.001). The in-hospital mortality was high in the last two groups (9.8% and 13.2% respectively) as compare to no in-hospital mortality in the first two groups, p=0.004. Non of the patients in risk group 1 and 2 required intra-aortic balloon counterpulsation.

Conclusions:
Patients presented with acute STEMI with TRI <17.5 at presentation and underwent successful PPCI for STEMI did not encounter any in-hospital MACE and may probably benefit from observation in step-down unit and the implication may result in substantial cost savings.
Abstract 9133: Abnormal Response of Superior Sinoatrial Node to Sympathetic Stimulation is a Characteristic Finding in Patients with Atrial Fibrillation and Symptomatic Bradycardia
Authors: Joung Boyoung , Shim Jaemin , Hwang Hye jin , Pak Hui-Nam , Lee Moon-Hyoung , Shen Changyu , Lin Shien-Fong , Chen Peng-Sheng
Published: April 2024

Introduction:
We hypothesize that unresponsiveness of superior sinoatrial node (SAN) to sympathetic stimulation is strongly associated with the development of symptomatic bradycardia in patients with atrial fibrillation (AF).

Methods and Results:
We performed 3-dimensional endocardial mapping in healthy control (Group 1, n=10) and in patients with AF without (Group 2, n=57) or with (Group 3, n=15) symptomatic bradycardia at baseline and during isoproterenol infusion. Sympatomatic bradycardia includes cardiac syncope, presyncope or dizziness associated with either sinus bradycardia (<40 bpm; n=7) or prolonged sinus pauses (>3.0 seconds; n=8) Corrected SAN recovery time (CSNRT) was abnormal (> 550ms) in 0%, 11% and 36% of groups 1, 2 and 3, respectively (p=0.02). At baseline, 90%, 36% and 7% (p<0.001) of the patients had multicentric SAN activation patterns. For groups 1, 2 and 3, respectively, the median distance from the superior vena cava-right atrial junction to the most cranial earliest activation site (EAS) was 5.0 (25-75 percentile range, 3.5-21.3) mm, 10.0 (4-20) mm and 17.5 (12-34) mm at baseline (p=0.01), and was 4.0 (0-5) mm, 5.0 (1-10) mm and 15.0 (5.4-33.3) mm during isoproterenol infusion (p=0.01), suggesting upward shift of EAS during isoproterenol infusion. However, while the EAS during isoproterenol infusion was at the upper 1/3 of crista terminalis in 100% of Group 1 and 78% of Group 2 patients, only 20% of the groups 3 patients moved EAS to that region (p < 0.001). We analyzed the comparative efficacy of CSNRT and 3D mapping in differentiating Group 2 and Group 3 patients. The sensitivity and specificity of CSNRT test are 35% and 89%, respectively, and of the 3D mapping test are 78% and 78%, respectively.

Conclusions:
Superior SAN serves as the EAS during sympathetic stimulation in normal patients and in most patients with AF without symptomatic bradycardia. In contrast, unresponsiveness of superior SAN to sympathetic stimulation is a characteristic finding in patients with AF and symptomatic bradycardia.
Abstract 9138: QT Interval Duration and Incident Mortality in the Framingham Heart Study
Authors: Noseworthy Peter A , Peloso Gina M , Hwang Shih-Jen , Larson Martin G , Levy Daniel , O'Donnell Christopher J , Newton-Cheh Christopher
Published: April 2024

Background:
The association between QT interval and mortality has been demonstrated in multiple large, prospective population-based studies using Bazett's heart rate correction, but the strength of the association varies considerably among studies. We examined this relationship in the Framingham Heart Study.

Methods and Results:
Participants in the first (original cohort, n = 2,415) and second generation (offspring cohort, n = 4,478) cohorts examined in the early 1970s were included in this study. Using Cox proportional hazards regression adjusting for age and sex, a 20 msec increase in QTc (using Bazett's correction; QT/RR
1/2
interval) was associated with increased risk of all-cause mortality (HR 1.15, 95% CI 1.12-1.19, p = 7.6x10
-17
), CHD mortality (HR 1.18, 95% CI 1.08-1.30, p = 0.0003), and sudden cardiac death (HR 1.20, 95% CI 1.04-1.39, p = 0.01). However, additional adjustment for heart rate, either by additional adjustment of the QTc for RR interval, or use of linear regression of QT on RR interval, attenuated the associations with all-cause mortality (HR 1.10, 95% CI 1.06-1.15, p= 3.6x10
-6
, Figure), CHD mortality (HR 1.11, 95% CI 0.99-1.24, p= 0.07) and SCD (HR 1.16, 95% CI 0.97-1.40, p= 0.11).

Conclusion:
In the FHS (mean follow up 27.35 years), there is evidence for a graded relationship between QTc and all-cause mortality, CHD death, and SCD, however, this effect is considerably attenuated by additional adjustment for RR interval. These findings demonstrate that residual confounding by heart rate overestimates the effect on mortality when using Bazett's heart rate correction.
Abstract 9139: Mitochondrial Aldehyde Dehydrogenase 2*2 Allele Carriers Possess Better Cardioprotection Results After Cardioplegic Arrest During Open-Heart Surgery
Authors: Zhang Hao , Gong Dingxu , Zhang Yujian , Li Shoujun , Yan Fuxia , Hu Shengshou
Published: April 2024

Introduction:
Previous rodent studies indicated aldehyde dehydrogenase-2 (ALDH2) activation conferred cardioprotection. About 40% East Asians carry an ALDH2*2 allele to result in a reduced ALDH2 activity. The influence of ALDH2*2 on human cardioprotection after cardioplegia has not been studied, and we hypothesized that ALDH2*2 allele could have an effect on it.

Methods:
A prospective cohort of East Asians with a diagnosis of Tetralogy of Fallot (n=80) undergoing elective surgical repair were genotyped. All subjects followed the same operation and ICU protocol. Myocardium samples were dissected after cardioplegic arrest and detailed clinical information were collected. Myocardium ALDH2 activity, 4-hydroxy-2-nonenal (4-HNE) adducts and glutathione (GSH) levels, and expressions of ALDH2 and activating transcription factor-4 (ATF4), a key transcriptional regulator for GSH formation, were determined by spectrophotography, ELISA, and western blotting respectively. All the experimental and clinical results were compared between ALDH2*2 carriers and non-carriers.

Results:
ALDH2*2 allele presented in 38.75% of the patients. Myocardium ALDH2 enzyme activity difference among ALDH2*2 carriers and non-carriers disappeared during cardioplegia. ALDH2*2 carriers expressed less ALDH2 and more ATF4, and they got lower 4-HNE adducts levels and higher GSH levels. A lower postoperative inotropic score and troponin I level, and shorter length of hospital stay were observed in ALDH2*2 carriers (Table).

Conclusions:
In order to antagonize oxidative stress, ALDH2*2 carriers developed a compensatory larger myocardium GSH pool through ATF4 activation. When ALDH2 activity was impaired during cardioplegia, this larger GSH pool leaded to unexpectedly better cardioprotection results on ALDH2*2 carriers. ALDH2 genotype might be served as a genetic predictor for cardioprotection, and new cardioprotective strategies for ALDH2*2 non- carriers should be developed.
Abstract 9151: Presentation, Management, and Outcomes of 25,748 Acute Coronary Syndrome Admissions in Kerala, India: Results from the Kerala ACS Registry
Authors: Mohanan P.P. , Mathew Rony , Harikrishnan S. , Krishan M.N. , Zachriah Geevar , Joseph Jhony , Huffman Mark D , Eapen Koshy , Abraham Mathew , Menon Jaideep , Manoj P. , Jacob Sonny , Prabhakaran Dorairaj ,   Kerala ACS Registry Investigators
Published: April 2024

Introduction:
There are limited contemporary data on the presentation, management, and outcomes of acute coronary syndrome (ACS) admissions in India. The Cardiological Society of India - Kerala Chapter developed a prospective ACS registry to address this gap.

Hypothesis:
We hypothesized that patients presenting with STEMI would be younger, have lower education levels, be more likely to undergo PCI, and be more likely to die during index hospitalization and 30-day follow-up than patients with non-STEMI and unstable angina.

Methods:
We prospectively collected data on 25,748 consecutive ACS admissions from 2007-2009 in 125 hospitals in Kerala, India.

Results:
The Table describes the differences among STEMI (37%), non-STEMI (31%), and unstable angina (32%) patient presentation, management, and outcomes. Mean (SD) age at presentation was 60 (12) years and did not differ among ACS types, but unstable angina admissions were more likely to be men and have a prior history of diabetes and MI than other ACS types. In-hospital aspirin and clopidogrel rates were high (>90%) and similar across ACS types, whereas in-hospital heparin and beta-blocker rates were lower overall (<75%) and more commonly used in non-STEMI and unstable angina admissions compared with STEMI admissions. Angiography rates were similar across the 3 groups, and PCI rates were slightly higher in STEMI (13%) compared with non-STEMI (12%) and unstable angina (11%). Discharge medication rates were variable and generally suboptimal (<80%). In-hospital and 30-day death rates were highest for STEMI admissions (8.2% and 14.6%, respectively). Presentation, management, and outcomes differ from data from a US-based cohort such as the NCDR ACTION Registry-Get-With-The-Guidelines.

Conclusions:
In conclusion, these data represent the largest ACS registry in India to date and will serve as the baseline for future ACS quality improvement efforts in Kerala.
Abstract 9165: Short and Long-Term Case Fatality of Thoracic Aortic Dissection: A Thirteen Year Statewide Study
Authors: Shindler Daniel M , Gandhi Sampada K , Cheng Jerry Q , Cosgrove Nora M , Deng Yingzi , Cabrera Javier , Kostis John B ,   For the Myocardial Infarction Data Acquisition System (MIDAS) Study Group
Published: April 2024

Objectives.
We examined in-hospital and long-term case fatality in patients aged ≥ 20 years admitted with a first-time diagnosis of thoracic aortic dissection (AoD) to all non-federal hospitals in New Jersey (NJ) between 1995 and 2007 using a statewide database.

Methods.
The Myocardial Infarction Data Acquisition System (MIDAS) database was used to identify demographic characteristics, comorbidities and the presence of hypertension (HT) and diabetes mellitus (DM) among AoD patients. Deaths were ascertained by matching the MIDAS records to death information from NJ Death Registration Files.

Results.
The 2,373 cases of AoD observed during the study period were categorized into four groups: DM alone (n=41), HT alone (n=1,499), both DM and HT (n=237), neither of the conditions (n=596). Mortality from the index admission was high in all groups: 16.9% died in hospital, 19.6% within 30 days, 30.4% within 1 year and 43.8% within 5 years (Figure 1A). Figures 1B, 1C and 1D show the survival probability among 4 groups using Kaplan-Meier estimates. After adjusting for all covariates in the model, important predictors of mortality among all AoD patients were prior history of: hypertension, chronic renal disease, atrial fibrillation and arrhythmia. Of those who were discharged alive, 16.2% died within 1 year and 32.4% died within 5 years. Approximately 64% of the post discharge deaths were due to a cardiovascular cause, mostly comprised of coronary heart disease (35.6%), aortic aneurysm or dissection (33.4%) and cerebrovascular disease (9.3%). The remaining 36% of the post discharge deaths were due to a non-cardiovascular cause such as cancer, COPD, and renal disease.

Conclusions.
Thoracic aortic dissection patients, including a previously unstudied diabetic subgroup, have a poor five year prognosis. A majority of the post-discharge deaths were due to a cardiovascular cause and a significant proportion of those were due to recurrent aortic dissection.
Abstract 9168: Echocardiography-Based Screening for Rheumatic Heart Disease: A Sensitive and Cost-effective Way to Reduce Disease Burden in the Developing World
Authors: Beaton Andrea , Okello Emmy , Batambuze Winston , Lwabi Peter , Mondo Charles , McCarter Robert , Sable Craig
Published: April 2024

Introduction:
Early detection and prophylaxis of rheumatic heart disease (RHD) can prevent devastating sequlae. Echocardiography (echo)-based screening improves detection of RHD in endemic regions, but the best protocol to maximize case detection and minimize over-diagnosis is unclear. The recent WHO/NIH 2006 guidelines have yet to be assessed in a large-scale prevalence study. We used these guidelines and identified risk factors for occult RHD in a large cohort of Ugandan school children. We tested two hypotheses: echo screening for RHD is inexpensive and more sensitive than auscultation and laboratory testing; and RHD is more prevalent in lower socioeconomic groups.

Methods:
Auscultation and portable ultrasound were used to screen students, ages 5 to 16, from randomly selected schools in Kampala, Uganda. Positive cases followed up at Kampala's main referral hospital. Studies were blindly reviewed by three independent cardiologists. Categories for disease likelihood - definite, probable, and possible - were assigned based on the 2006 guidelines. Detection rates by auscultation and echo imaging were compared. ASO titers and markers of inflammation (ESR/CRP) were obtained on follow-up cases. The impact of socioeconomic status was examined.

Results:
Screening of 4869 of 5006 (97%) eligible students occurred in 6 schools over a 4-month period. Screening was abnormal in 130 children. On follow-up, 18 had congenital heart disease, 40 were normal, and 72 had possible, probable, or definite RHD. Echo detected 3 times as many cases of RHD than auscultation alone: 72 (1.5%) vs.23 (0.5%), p<0.001. Children with RHD were older (10.1 yr vs. 9.3 yr, p=0.002). Most cases (98%) involved only the mitral valve. Children from lower socioeconomic schools had RHD more frequently (2.7% vs. 1.4%, p=0.036) and had more advanced disease (64% vs. 26%, p<0.001). Labs had no significance. Each study cost $0.18 (echo machine, nursing, and transportation).

Conclusions:
This is the largest single-country childhood RHD prevalence study to date. Our data support the inclusion of echo in screening protocols and identify lower socioeconomic groups as the most vulnerable. Efforts should be made to promote more widespread use of echo screening, which can be done for only pennies a student.
Abstract 9173: Neurological and Cardiac Functional Status After Extracorporeal Membrane Oxygenation in Children with Heart Disease
Authors: Alshehri Saleh S , Shetty Rakshay , Caldarone Christopher A , Gruenwald Colleen , Manlhiot Cedric , McCrindle Brian W , Schwartz Steven M , Van Arsdell Glen S , Sivarajan Venkatesan B
Published: April 2024

Introduction:
There are limited outcomes data following hospital discharge after extracorporeal membrane oxygenation (ECMO) in children with heart disease.

Hypothesis:
Children with heart disease who are hospital survivors of ECMO have ongoing mortality, but minimal functional residua.

Methods:
We reviewed data of all children with heart disease receiving venoarterial ECMO for a cardiac indication between 2001-2008. Pre-ECMO characteristics, ECMO details, complications and outcomes were abstracted from institutional databases and medical records. Univariate and multivariable analyses to determine factors associated with hospital survival and neurological outcomes using the Pediatric Cerebral Performance Category (PCPC) score were performed.

Results:
184 ECMO episodes (163 patients) occurred at a median ( 25
th
, 75
th
%ile) age of 0.36 (0.04, 2.2) years; indications were cardiomyopathy (22%) and post-cardiotomy (66%). Cardiac arrest prompted 100 (54%) ECMO episodes in 86 patients. The median duration of CPR was 31 minutes. The median ECMO duration was 4 days. ECMO complications included intracranial hemorrhage (22%), ischemic brain injury (27%), seizures (27%), pulmonary or gastrointestinal bleeding (15%) and need for renal replacement therapy (49%). Of the total inception cohort, 63 (41%) survived to hospital discharge; 58 (36%) were alive at a median follow-up of 3.6 years with the majority (81%) having a PCPC score ≤ 2. Of the 86 patients who had cardiac arrest, 28 (33%) survived to hospital discharge; 22 (26%) were alive at a median follow-up of 3 years with the majority (81%) having a PCPC score ≤ 2. At follow-up, 55 (82%) were in pediatric NYHA Class ≤ 2 heart failure. Factors associated with hospital survival were cardiomyopathy (OR=2.2, p=0.01) and biventricular physiology (OR=1.9, p=0.006). A pre-ECMO diagnosis of cardiomyopathy was associated with a lower PCPC score at 6 months (EST: -0.24, p=0.0007), while ECMO for cardiac arrest was associated with a higher PCPC score at (EST: 0.16, p=0.008) 6 month follow-up.

Conclusion:
Children with heart disease who survive to hospital discharge after ECMO have ongoing early mortality; despite these concerns, survivors have good quality neurological outcome and cardiac functional status.
Abstract 9185: Is Suboptimal Adherence to Weight Monitoring and/or Weight-Based Diuretic Self-Adjustment Associated with Heart Failure-Related Emergency Department Visits or Hospitalizations?
Authors: Jones Christine D , Holmes George M , DeWalt Darren A , Erman Brian , Broucksou Kimberly A , Hawk Victoria , Wu Jia-Rong , Cene Crystal W , Pignone Michael
Published: April 2024

Background
Heart failure (HF) self-care interventions that include daily weights and diuretic self-adjustment to manage volume status can improve outcomes, but suboptimal adherence may limit their effectiveness. We sought to evaluate the association of 1) adherence to weight monitoring, and 2) adherence to a weight-based diuretic self-adjustment plan (WBDSA) with HF-related Emergency Department (ED) visits or hospitalizations.

Methods
We performed a case-control analysis nested in a HF self-care clinical trial. Participants received HF education over one year that covered topics including daily weight monitoring and personalized WBDSA plans. All participants were to record daily weights and loop diuretic doses in a specialized diary. Cases were 7-day periods preceding HF-related ED visits or hospitalizations determined by masked outcome adjudication. Controls were 7-day periods free of ED visits or hospitalizations and were matched to cases 10:1 for age, gender, NYHA class, and study site. Weight monitoring adherence required recording a weight; WBDSA adherence required recording a correct diuretic dose based on the WBDSA plan. Weight monitoring and WBDSA adherence were determined over 7 days and dichotomized into <6 versus >= 6/7 days of adherence. We used logistic regression to evaluate the odds of weight monitoring and WBDSA adherence in cases compared to controls and adjusted for age, gender, NYHA class, study site, literacy, socioeconomic ladder, systolic HF, cardiovascular disease, and chronic kidney disease.

Results
Among 303 participants, we identified 81 eligible cases [12 ED visits (15%) and 69 hospitalizations (85%)] in 54 patients. Weight monitoring adherence (OR 0.43, 95% CI 0.23, 0.81) and WBDSA adherence (OR 0.36, 95% CI 0.16, 0.82) were both associated with lower adjusted odds of a HF-related ED visit or hospitalization. Results were similar in unadjusted models for both weight monitoring adherence (OR 0.54, 95% CI 0.31, 0.95) and WBDSA adherence (0.36, 95% CI 0.16, 0.81).

Conclusions
Adherence to daily weight monitoring and WBDSA was associated with lower odds of ED visits or hospitalizations related to HF. Enhancing adoption and adherence for these self-care behaviors may be an important step in reducing HF-related morbidity.
Abstract 9192: Genetic Ancestry is Associated with Left Ventricular Mass Among Hispanic Subgroups: The Multi-Ethnic Study of Atherosclerosis
Authors: Rodriguez Carlos J , Stewart William C , Bluemke David A , González-Burchard Esteban , Lima Joao A , Arnett Donna K
Published: April 2024

Hispanics represent a recently admixed population of European, Native American and African parental populations. Hispanics have higher left ventricular mass (LVM) than non-Hispanic whites, and this relationship persists across Hispanic subgroups. However, the contribution of genetic ancestry to LVM across Hispanic subgroups is not known.

Methods
- We examined 705 Hispanic participants. Percent genetic ancestry for each Hispanic subgroup was estimated with 199 ancestry informative markers using the population genetics analysis program STRUCTURE. LVM from cardiac MRI was evaluated as a continuous measurement, with allometric methods that model height and weight in a regression analysis. Associations between ancestry and LVM were evaluated through linear regression models consisting of age, gender, both highest education level and annual income, and diabetes treatment, hypertension, physical activity, and body mass index.

Results
- Mexicans along with Central Americans had the highest Native American (74%) ancestry. Caribbean-Hispanics (Dominicans, Puerto Ricans and Cubans) had the highest African (35%) ancestry. Among Caribbean Hispanics (in age and gender adjusted analysis), each SD increase in African ancestry was associated with a 3.4 unit increase in LVM (p < 0.03). Among Mexican-origin Hispanics, each SD increase in Native American ancestry was associated with a 2.4 unit increase in LVM (p = 0.06). These relationships were not attributable to differences in socioeconomic status or clinical factors. In Caribbean-Hispanics, African ancestry explains 9.6% of the total variance in LVM in fully adjusted models. In Mexican-origin Hispanics, Native American ancestry explains 13.0% of the total variance in fully adjusted models. There was insufficient evidence in these data to detect an association between genetic ancestry and LVM in Central/South Americans.

Conclusion
- African and Native American ancestry was significantly associated with increasing LVM among Caribbean-Hispanics and Mexican-origin Hispanics, respectively. The findings persisted after accounting for LVM risk factors. These results highlight the heterogeneity of the Hispanic population and the relative importance of genetic ancestry in assessing LVM risk.
Abstract 9213: Risk of Gastrointestinal Conditions Among Patients with Atrial Fibrillation
Authors: Laliberté François , Moore Yuliya , Dea Katherine , LaMori Joyce C , Mody Samir H , Jones JaCinda L , Arledge Michelle D , Damaraju C V , Duh Mei Sheng , Schein Jeff R , Lefebvre Patrick
Published: April 2024

Objective:
There are limited data suggesting that gastrointestinal (GI) conditions are common in patients with atrial fibrillation (AF). However, AF patients are generally older, and, many agents utilized by patients with AF are known to increase the risk of GI events. The objective of this study was to describe the risk of GI events among patients with AF.

Design:
An analysis of insurance healthcare claims from the Thomson Reuters MarketScan
®
database was conducted. Over the period from 2005 to 2009, all subjects aged ≥18 years as of the date of first AF diagnosis, with ≥180 days of continuous insurance coverage prior to the index AF and no GI event within 180 days of the index AF were selected. GI events were identified from claims with a primary or secondary diagnosis code for any GI condition and for the subset of GI conditions consistent with dyspepsia (upper abdominal pain, abdominal pain, abdominal discomfort and dyspepsia). The risk of GI events was assessed with incidence rates (IRs) (new GI cases / patient-years of observation). Subgroup analyses were performed with respect to gender, age and CHADS
2
score.

Results:
A total of 413,168 patients with AF and no GI event in the 180-day baseline period were identified. The mean (median; SD) age of all patients with AF was 67.7 years (69; 15); 43% were female. During follow-up (mean of 563 days), IRs of any GI event and dyspepsia for patients with AF but no GI symptoms at baseline were 38.8 and 14.7 events per 100 patient-years. Corresponding IRs of any GI events for female and male were 43.6 and 35.5; for patients in the age groups below 65, 65-74, 75-84 and ≥85 years IRs were 32.3, 38.9, 44.6 and 52.7; for patients with CHADS
2
score of 0, 1-2, 3-4 and 5-6 IRs were 30.3, 41.6, 56.9 and 74.5, respectively. At baseline, 257,357 patients (62%) had at least one medication dispensed which may cause GI tolerability issues.

Conclusions:
In this large claims database, AF was associated with a high IR of GI events. A rising trend in IR was observed with increasing age and CHADS
2
score. Higher propensity for GI events (such as dyspepsia) and agents that selectively cause higher symptomatic GI rates may relate to poor medication adherence in AF patients. Therefore, prescribers should take subgroup characteristics of this population into consideration.
Abstract 9236: Receptor Tyrosine Kinase Signaling Causes Cardiac Hypertrophy in Adult
Drosophila
Authors: Yu Lin , Daniels Joseph P , Wolf Matthew J
Published: April 2024

Abnormalities in receptor tyrosine kinase (RTK) signaling are associated with dilated cardiomyopathies and cardiac hypertrophy in humans and mouse models. We have developed strategies based on fruit fly genetics to identify genes that cause cardiac abnormalities in order to better understand suppressors of cardiomyopathic phenotypes. To characterize the role of RTK pathway in adult
Drosophila
heart function, we expressed dominant negative or constitutively active EGFR (DN-EGFR or EGFR
Act
) specifically in the fly heart using tinC-Gal4 drivers. DN-EGFR flies had enlarged hearts and poor systolic function as assessed by optical coherence tomography. Interestingly, the cardiac-specific expression of EGFR
Act
resulted in significantly reduced eclosion rates and poor survival of adult escapers, which die within 48hrs. Moreover, EGFR
Act
adult escapers showed abnormal cardiomyocyte myofibrils, smaller heart lumens and significant increases in concentric wall thickness consistent with cardiac hypertrophy. The number of cardiac nuclei among hearts expressing EGFR
Act
was the same as controls, suggesting the effect was not due to proliferation. Since EGFR stimulation results in the activation of Ras and multiple downstream components including Raf-ERK, Ral-GDS and PI3K-AKT, we examined the effects of cardiac-specific expression of constitutively active Ras85D (Ras85D
V12
), gain of function Raf (Raf
GOF
) and constitutively active PI3K (PI3K
Act
). Ras85D
V12
and Raf
GOF
, but not PI3K
Act
phenocopied the effects of EGFR
Act
resulting in abnormal cardiac myofibrils, smaller heart lumens and thicker concentric wall. To our knowledge, our findings represent the first evident of cardiac hypertrophy in the fruit flies. These results suggest that Ras-mediated activation of Raf-ERK may be a major contributor to the abnormal cardiac hypertrophy phenotype. Our ongoing studies are focused on the rescue of the Ras85D
Act
phenotype by ERK inhibition and the identification of gene transcripts that correlate with cardiac hypertrophy in adult
Drosophila
.
Abstract 9250: Endocardial Electrogram Characteristics Indicating an Epicardial Origin of Focal Ventricular Arrhythmias
Authors: Sauer William H , Tzou Wendy , Schuller Joseph L , Heath Russell , Katz David , Nguyen Duy T , Aleong Ryan G , Varosy Paul D
Published: April 2024

Introduction:
While most ventricular arrhythmias (VA) can be ablated successfully using an endocardial (ENDO) approach, epicardial (EPI) mapping and ablation is sometimes required. There may be clues on the surface electrocardiogram related to intrinsicoid deflection and QRS width; however, identification of an EPI origin of VA with certainty remains problematic, and there are no reported ENDO electrogram (EGM) characteristics that may direct ablation strategy.

Methods:
All patients referred for ablation of ventricular tachycardia or frequent ventricular ectopy from June 2006 through July 2010 were evaluated. Only patients with completed electroanatomical activation maps of a focal VA from ENDO and EPI were included. EGMs recorded by a bipolar mapping catheter in the area of earliest ENDO activation were analyzed and compared to the area of early EPI activation.

Results:
There were 17 patients with completed ENDO and EPI electroanatomical maps of a focal VA identified. We identified 3 characteristics from ENDO mapping that consistently indicated an EPI VA origin: 1) Diffusely early activation (> 2cm2 region of sites with equally earliest activation within 10 msec; figure); 2) Sequence of a far-field EGM followed by a near-field EGM in the region of earliest ENDO activation; and 3) Inability to capture the far-field component of the earliest ENDO EGM (stimulus-QRS < egm-QRS time) or reproduce the PVC or VT QRS complex morphology with pacing at the earliest ENDO activation site.

Conclusions:
The presence of a diffuse area of early activation and inability to capture a far-field electrogram from the endocardium indicates an epicardial origin of a focal ventricular arrhythmia.