bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15714: Electrical versus Anatomic Left Ventricular Hypertrophy Associated With Sudden Death
Authors: Narayanan Kumar , Darouian Navid , Uy-Evanado Audrey , Teodorescu Carmen , Reinier Kyndaron , Chugh Harpriya , Gunson Karen , Jui Jonathan , Chugh Sumeet S
Published: April 2024

Introduction:
We have previously reported that electrocardiographic (ECG) left ventricular hypertrophy (LVH) can occur in the absence of increased LV mass (echocardiographic LVH), and conveys unique risk of sudden cardiac arrest (SCA). We further characterized this adverse “electrical remodeling” by comparing SCA cases with isolated electrical vs. isolated anatomic LVH.

Hypothesis:
Cases with electrical versus anatomic LVH have distinct clinical profiles

Methods:
Adult SCA cases were prospectively ascertained from multiple sources in a Northwestern US metro area (population approx. 1 million). Clinical/demographic information was obtained from medical records. ECGs, prior and unrelated to SCA were reviewed in blinded fashion to detect ECG-LVH (Sokolow-Lyon criteria). LV mass, obtained from echocardiograms was used to identify echo-LVH (LV Mass Index > 134 g/m2 men; 110 g/m2 women). Cases with isolated ECG-LVH versus isolated echo-LVH were compared to identify distinctive characteristics. Patients who had LVH by both tests and those without LVH by either test were excluded.

Results:
Among 323 SCA cases (2002-14; 69.0 ± 13.5 yrs; 66.9% male) with adequate information available, echo-LVH was present in 134 (41.5%) cases and ECG-LVH in 58 (18.0%) cases. After elimination of cases with LVH by both modalities, 103 (31.9%) cases had isolated echo-LVH while 27 (8.3%) had isolated ECG-LVH. Compared to cases with isolated ECG-LVH, isolated echo-LVH cases had lower LV ejection fraction (45.2 ± 16.9 vs. 53.0 ± 14.8%; p=0.03), were more likely to be current smokers (30.8 vs. 8.7%; p=0.06), obese (41.7 vs. 25.9%; p=0.12) and African-American (19.4 vs 7.4%; p=0.15). There were no significant differences between the two groups for systemic hypertension (78.6 vs. 88.9%; p=0.23), age, sex, diabetes, renal disease, coronary artery disease or prior myocardial infarction. Prescription of anti-hypertensive medications including ACE inhibitors, angiotensin receptor blockers and beta blockers were equally likely in both groups.

Conclusions:
Patients with electrical vs. anatomic LVH appear to have distinct clinical profiles. These findings can serve as a foundation for further investigation of genetic and acquired mechanisms of electrical LVH leading to sudden death.
Abstract 15716: Tristetraprolin Protects the Heart Against Iron Deficiency by Reducing Expression of Iron-requiring Proteins and Optimizing Cellular Iron Utilization
Authors: Sato Tatsuya , Bayeva Marina , Ardehali Hossein
Published: April 2024

Background:
Iron deficiency is the most common nutrient deficiency in the world, however, patients with severe iron deficiency generally have normal cardiac function. This suggests that a mechanism exists in the heart that maintains cardiac iron levels despite systemic iron deficiency, however, the mechanism for this adaptation of the heart to iron deficiency is not known. We recently discovered an mRNA-binding protein tristetraprolin (TTP) to mediate iron utilization within an iron-deprived cell independently of the canonical iron regulatory proteins (IRPs). Here, we hypothesized that TTP protects the heart against iron deficiency through intracellular conservation of iron, and that disruption of this pathway will make the heart vulnerable to low-iron states.

Results:
Consistent with the above hypothesis, we demonstrated that hearts of TTP knockout mice have normal baseline function, yet deteriorate when subjected to iron deficiency. On contrary, iron-deficient TTP WT mice show no decline in cardiac function in spite of significant reduction in iron levels. Since TTP is known to reduce protein expression through mRNA degradation, we hypothesized that it halts expression of iron-consuming proteins, reducing overall cardiomyocyte’s iron requirements. We identified three mitochondrial iron-requiring proteins to be negatively regulated by TTP: NDUFS1 (part of complex I), UQCRFS1 (part of complex III), and mitochondrial aconitase (part of the TCA cycle). Specifically, we showed that TTP binds to and degrades mRNAs of these targets. This is based on data that the steady state level of the mRNAs for these proteins are decreased with iron chelation, but do not change with TTP deletion. Additionally, mRNAs of these proteins are protected against after actinomycin-D treatment with TTP deletion. RNA co-immunoprecipitation studies confirmed TTP binding to the mRNAs of these proteins. Thus, in the absence of TTP, these proteins continue to be expressed and act as “iron sinks” in a cell that is already iron deficient.

Conclusions:
Our results, for the first time, provide the mechanism of cellular adaptation to iron deficiency, and demonstrate a major role for TTP in this process by regulating mitochondrial proteins.
Abstract 15764: Aortic Valve Intervention for Severe Aortic Stenosis Improves Outcomes Following Non-cardiac Surgery
Authors: Luis Sushil A , Pislaru Sorin V , Scott Christopher G , Kane Garvan C , Abel Martin D , Nkomo Vuyisile T , Pellikka Patricia A
Published: April 2024

Background:
Non-cardiac surgery (NCS) in patients with severe aortic stenosis has traditionally been associated with high perioperative mortality. Aortic valve replacement is recommended prior to elective NCS, but the impact of this strategy has not been systematically assessed.

Methods:
A retrospective review was performed of all patients with severe aortic stenosis undergoing major NCS at Mayo Clinic between 2000 and 2013. Patients undergoing aortic valve intervention (AVI) prior to NCS were compared to those undergoing surgery without prior AVI (control). Patients undergoing emergency surgery were excluded. Primary endpoint was occurrence of major adverse cardiac events (MACE; combination of death, stroke, myocardial infarction, new/worsening heart failure, ventricular arrhythmia) within 30 days of NCS; secondary endpoints were mortality at 30 days and 1 year after NCS.

Results:
180 patients (age 74.5 ± 10.5 years, 64% male) who underwent NCS within 12 months after AVI, were compared to 232 patients (age 76.6 ± 10.7 years, 56% male) in the control group. Patients undergoing AVI were more often symptomatic than controls (41% vs 26%, p = 0.002). MACE was significantly higher in the control group (21.6% vs 5.6%, p < 0.001), mainly due to the increased risk of heart failure in the postoperative period in this group (18.5% vs 2.2%, p < 0.001). There was no significant difference in the rate of myocardial infarction (1.7% vs 0.6%, p = 0.39), ventricular arrhythmia (0.9 % vs 0 %, p = 0.51) or stroke (0.9 % vs 0 %, p = 0.51). Kaplan-Meier assessment demonstrated no significant difference at 30 days but a reduction in 1 year mortality in the AVI group compared to the control group (Figure).

Conclusions:
Pre-operative AVI for severe aortic stenosis results in reduced heart failure and improved 1 year survival. However, other MACE and 30 day mortality appears unchanged. Pre-operative AVI should be considered in symptomatic patients, where the benefit of AVI is demonstrated to be greatest.
Abstract 15777: Preconditioning With Whole Body Periodic Acceleration (pGz) Protects Cardiomyocytes From Hypoxia-Reoxygenation Injury
Authors: Lopez Jose R , Kolster Juan , Uryash Arkady , Altamirano Francisco , Adams Jose A
Published: April 2024

Hypoxia and Reoxygenation (H-R) injury of the heart induces increase in diastolic Ca
2+
([Ca
2+
]
d
, and reactive oxygen species (ROS) leading to cellular death and myocardial dysfunction. pGz is the repetitive head-foot motion of the body inducing pulsatile shear stress, activating endothelial nitric oxide synthase (eNOS) to produce small quantities of eNO. eNO is cardioprotective and active in varied signaling pathways. We showed that preconditioning with pGz (pre-pGz) decreased myocardial injury from focal myocardial injury (MI) and cardiac arrest and increases the level and activity of endogenous antioxidants

Hypothesis:
pre-pGz confers cardioprotection in a cellular model of H-R injury.

Methods:
Mice (n=30) were randomized to pGz (f=480cpm, Gz 3.0mt/sec
2
,1 hr /d for 8 days) or none (CONT). Cardiomyocytes were isolated and exposed to 45 min hypoxia, followed by 15min reoxygenation (H-R). Resting membrane potentials (Vm) and [Ca
2+
]
d
were measured with microelectrodes. Intracellular ROS and glutathione peroxidase activity (GPx) were measured during normoxia and after H-R. In a separate group of mice, L-NAME was administered for 5 days along with pre-pGz prior to H-R (L-NAME+pGz+H-R).

Results:
Resting membrane potentials (Vm) were decreased by H-R and restored by pre-pGz. A 15x (fold) increase in [Ca
2+
]
d
and 5x increase in ROS production occurred in H-R that was blunted by pre-pGz. GPx activity was decreased but pre-pGz restored it. Pretreatment with L-NAME to pre-pGz animals abolished the effects of pGz. (FigureM±SD***p<0.001)

Conclusion:
Cardioprotection by pGz from H-R injury is in part due to a decrease in membrane depolarization, improved Ca
2+
homeostasis and reduction of ROS as well as increasing the level and activity of antioxidants. Such benefits are partially mediated via NO pathway. pGz is a novel, method of eliciting cardioprotection in hypoxic injury.
Abstract 15802: Baseline Troponin T Levels Modulate the Effects of Implantable Cardioverter Defibrillator Shocks on All-cause Mortality
Authors: Nauffal Victor , Zhang Yiyi , Blasco Colmenares Elena , Spragg David D , Marine Joseph E , Butcher Barbara , Norgard Sanaz , Guallar Eliseo , Tomaselli Gordon F , Cheng Alan
Published: April 2024

Introduction:
Implantable cardioverter defibrillator (ICD) therapy (shocks or anti-tachycardia pacing (ATP)) has been associated with an increased risk for death. Whether this association is mediated by direct effects of ICD therapy, the underlying myocardial disease process that triggered the tachyarrhythmia, or both remains poorly understood.

Methods and Results:
We followed 736 patients from the Prospective Observational Study of ICDs (PROSE-ICD) over a median of 5.3 years for the occurrence of ICD therapy and all-cause mortality. Multivariable Cox proportional hazards models were used to calculate the risk-adjusted hazard ratio associated with the different types of ICD therapy, modeled as time-dependent covariates. Additionally, we tested for interaction between ICD shocks and baseline levels of cardiac troponin T (cTnT). Appropriate shock (HR=2.66 [1.77 - 3.98]; p<0.001) was associated with increased mortality, while appropriate ATP (HR=1.02 [0.49 - 2.13]), inappropriate ATP (1.11 [0.48 - 2.58]) and inappropriate shocks (0.81 [0.50 - 1.32]) were not. Independent of the underlying arrhythmia, the mortality effects of ICD shock therapy were strongly modulated by baseline levels of cTnT (p-interaction=0.02). Patients with baseline cTnT≥0.01ng/ml had a significant increased mortality risk associated with ICD shocks (HR=1.73 [1.01 - 2.97] p=0.046) while patients with cTnT<0.01ng/ml did not (HR=0.49 [0.18 - 1.31]). Furthermore, patients with 1 or multiple appropriate shocks and those with multiple inappropriate shocks had a significantly increased mortality risk only in the setting of elevated baseline cTnT≥0.01ng/ml (Figure 1).

Conclusions:
Elevated baseline cTnT increases the risk of death in patients experiencing ICD shocks regardless of the underlying triggering arrhythmia. These findings provide further insights into how the underlying myocardial substrate may affect the relationship between ICD shocks and all-cause mortality.
Abstract 15850: Sex-specific Transcriptional and Protein Regulation of Calcium Handling Leading to Sex Differences in Cardiomyocyte Death in Heart Failure
Authors: Kararigas Georgios , Molina Cristina E , Summer Holger , Baczko Istvan , Golz Stefan , Regitz-Zagrosek Vera
Published: April 2024

Mechanisms underlying sex differences in heart failure (HF) are poorly understood. Women appear to have better prognosis underlain by lower rates of apoptosis and necrosis than men. We hypothesized significant sex differences in left ventricular (LV) transcriptional and protein regulation of end-stage non-ischemic dilated cardiomyopathy (DCM) patients. We compared LV samples of age- and medication-matched male (
n
= 5) and female (
n
= 5) DCM patients with male (
n
= 10) and female (
n
= 8) controls. Pathway analysis of genome-wide expression profiling (adjusted
P
< 0.05) revealed induction of ECM-receptor interaction and several inflammatory pathways in male LVs, while oxidative phosphorylation and proteasome pathways were repressed. In female LVs, the Wnt and Hedgehog signaling pathways were induced, while the mTOR signaling pathway was repressed. Ca2+ signaling pathway was induced in both sexes. However, male LVs had a significantly higher induction of ca. 30% of genes encoding ion channels, accessory beta subunits and regulatory proteins vs. female LVs. Patch-clamp recordings in isolated ventricular myocytes (VMs) from DCM patients showed that while there were no sex differences in sarcoplasmic reticulum Ca2+ load, there was a 2-fold increase in L-type Ca2+ current density in male vs. female VMs (
n
= 6-8 cells/group; each cell originated from a different individual;
P
< 0.05). The cytosolic release of cytochrome
c
was significantly higher in male vs. female LVs (
P
< 0.05). In contrast, the anti-apoptotic protein BCL2 was significantly higher in female vs. male LVs (
P
< 0.05). Ca2+-mediated dephosphorylation of pyruvate dehydrogenase was higher in male vs. female LVs (
P
< 0.01) indicating higher Ca2+ uptake in male vs. female mitochondria. Given the known reduction of the L-type Ca2+ channel activity by endothelial NO synthase (eNOS), we also show higher eNOS levels in female vs. male LVs (
P
< 0.05). We conclude that Ca2+ handling is the target of sex-specific transcriptional and protein regulation, which plays a major role in sex-specific mitochondrial Ca2+ uptake, thereby leading to sex differences in cardiomyocyte death in HF.
Abstract 11336: Different Mechanisms of Torsade de Pointes Arrhythmias in the Drug-induced Chronic AV Block Dog
Authors: Vandersickel Nele , Bossu Alexandre , Dunnink Albert , van der Heyden Marcel A , Meijborg Veronique M , Beekman Jet D , de Bakker Jacques M , Vos Marc A , Panfilov Alexander V
Published: April 2024

Introduction:
The arrhythmia Torsade de Pointes (TdP) is responsible for >5% of all sudden cardiac deaths. However, the mechanism(s) underlying the TdPs is under debate. Clinical and experimental data suggest that TdP may be driven either by focal sources or by moving reentry. One way to study the mechanisms of TdP is to use the electrically remodeled canine heart after chronic AV block (CAVB), which has a high susceptibility for drug-induced TdPs.

Methods:
Five TdP-sensitive CAVB dogs were studied. In all animals, 66 needle electrodes were evenly distributed transmurally to record 240 unipolar local electrograms simultaneously. If the TdP was non-terminating after 10s, it was defibrillated. Software was developed to automatically detect activation times during the dofetilide-induced TdPs and to create 3D visualisations of the arrhythmia. For each episode of TdP, directed graphs of the wave propagation were created and loops were detected by using an iterative depth first search algorithm(Johnson). Interbeat intervals were computed by taking the average of the time intervals of activation for each electrode.

Results:
In total we analysed 53 TdPs: from those 9 were non-terminating (> 50 beats) and 44 self terminating. In all non-terminating TdPs reentry loops were identified. In the 44 self terminating TdPs reentry loops were found only in 6 (20±10 beats) cases, while in the 38 (7±4 beats) other cases TdP was driven by focal sources. Secondly, during reentry, excitation fronts were constantly present in the heart, while during ectopic TdP there was always a pause between the end of the previous wave and the beginning of the next wave (121±51 ms) during which excitation fronts were absent. Thirdly, we found that the interbeat intervals were significantly smaller for the cases where reentry loops were detected, then in the cases of the ectopic TdPs (221±21 versus 310±96 ms). Finally, in all cases where reentry loops were detected, the signal of certain electrodes had significantly smaller amplitude than the average amplitude under normal pacing, which via computer simulations could be related to the cores of the reentry loops.

Conclusions:
In the non-terminating TdPs reentry is always present, while paroxysmal TdP was in most of the cases based on ectopic activity (86%).
Abstract 11360: Pulmonary Vein-Dominant Structural Remodeling in Patients With Hypertrophic Cardiomyopathy and Atrial Fibrillation
Authors: Yoshida Kentaro , Tsuneoka Hidekazu , Tsumagari Yasuaki , Aonuma Kazutaka
Published: April 2024

Introduction:
Atrial fibrillation (AF) is prevalent in patients with hypertrophic cardiomyopathy (HCM). However, structural remodeling of the left atrium (LA) and pulmonary veins (PV) has rarely been investigated in this setting. This study aimed to identify differences in LA and PV remodeling between HCM and hypertensive heart disease (HHD) using 3D-CT.

Methods:
Included in this study are 33 patients with HCM, 25 patients with HHD, and 29 patients without any co-morbidities who were referred for catheter ablation of AF. ANP and BNP levels before ablation and Troponin T level after ablation were measured, and LA and PV diameters were 3-dimensionally determined.

Results:
LA diameters in the control group was shorter than that in the HHD or HCM group (Fig 1). The PV diameters were the longest in the HCM group (Fig 2). The PV/LA ratio was higher in the HCM group than the control or HHD group (PV-dominant remodeling) (Fig 3). All biomarkers were the highest in the HCM group (Fig 4).

Conclusions:
The stiff LA caused from atrial hypertrophy may account for higher levels of biomarkers and PV-dominant remodeling in HCM.
Abstract 11363: Association of Dietary Protein, Animal and Vegetable Protein With the Incidence of Heart Failure Among Postmenopausal Women
Authors: Barbour Mohamad Firas , Ashraf Farhan , Roberts Mary B , Allison Matthew , Martin Lisa , Johnson Karen , Valdiviezo Carolina , Eaton Charles B
Published: April 2024

Background:
Heart failure (HF) is a highly prevalent disease especially in post-menopausal women. A better understanding of nutrition-related factors associated with HF is needed. Misclassification of diet due to self-reports can be partially ameliorated by use of biomarker calibration equations.

Objectives:
This study evaluated prospectively the association between biomarker calibrated dietary protein intake and the incidence of heart failure in a cohort of postmenopausal women. In addition, we studied the effect of energy adjusted animal and plant based dietary protein and the incidence of HF.

Methods:
Study participants are postmenopausal women (n=103,878) who are free of Heart Failure at baseline, evaluated from 1993-1998 in the Women health Initiative (WHI). We used self-reported intakes of total dietary protein, animal protein, and vegetable protein based upon a Food Frequency Questionnaire (FFQ) and calibration equations for protein derived from urinary nitrogen excretion and energy calibration based upon doubly labeled water. The association between dietary protein intake and the incidence Heart Failure was evaluated using cox proportional hazards models, and treating age as a continuous variable within age strata due to Simpson’s paradox.

Results:
Among 103,878 women in the study sample, 1711 women developed HF through 2005. Incremental biomarker calibrated dietary protein consumption was associated with an increase in the risk for Heart Failure. An inverse association was found between higher intakes of energy adjusted vegetable protein and HF although this association wasn’t statically significant if the association was adjusted to BMI and diet quality.

Conclusion:
Higher total dietary protein intake (calibrated), appears to be associated with substantially increased heart failure risk while the vegetable protein intake appears to be protective against developing Heart Failure. Further studies are needed to explore this association.
Abstract 11369: Circulating Very Long-Chain Saturated Fatty Acids and Heart Failure
Authors: Lemaitre Rozenn N , McKnight Barbara , Fretts Amanda , Qureshi Waqas T , Siscovick David S , Sotoodehnia Nona , Psaty Bruce M , Mozaffarian Dariush
Published: April 2024

Introduction:
Myocardial fibrosis with apoptosis contributes to heart failure (HF), and ceramides, with their role in apoptosis, may contribute to this pathophysiological process. However, experimental studies show that ceramides carrying a VLSFA are in fact protective against apoptosis, providing strong evidence that very long-chain saturated fatty acids (VLSFA) impart different biological activity to ceramides.

Hypothesis:
Circulating VLSFA are associated with lower risk of HF.

Methods:
We addressed this hypothesis in the Cardiovascular Health Study (CHS), a prospective study of older adults (mean age 72 at entry) with repeated measures of plasma phospholipid fatty acids. Circulating fatty acids were measured at the study baseline in 1992-93, and again where possible, in the 6
th
year and 13
th
year of follow-up, in plasma phospholipids. We assessed the associations of three VLSFA, arachidic acid (20:0), behenic acid (22:0) and lignoceric acid (24:0), with risk of incident HF using Cox regression with time-dependent covariates and fatty acids.

Results:
The analyses included 4,060 CHS participants with fatty acid data at least at one time point. During 43,430 person-years, we identified 1228 incident HF. In analyses adjusted for age, sex, race, center, blood pressure, BMI, waist circumference, physical activity, smoking, history of coronary heart disease, atrial fibrillation, diabetes, and current use of antihypertensive medications, higher levels of 22:0 and 24:0 were associated with lower risk of incident HF (Table). With further adjustment for fatty acids previously found to be associated with HF, all three VLSFA were associated with lower risk of incident HF.

Conclusions:
Higher levels of circulating VLSFA are associated with lower risk of incident HF. These novel findings may open a new avenue of research into these little studied saturated fatty acids and their possible beneficial role in preventing HF.
Abstract 11382: Should We Close Left Atrial Appendage in Cardiac Surgery ? : Meta-analysis of 7466 Patients Who Underwent Open-heart Surgery
Authors: Ando Masahiko , Funamoto Masaki , Sundt Thoralf M
Published: April 2024

Introduction:
While percutaneous closure of left atrial appendage (LAA) can be a potential alternative to life-long anticoagulation in patients with atrial fibrillation (AF), comprehensive evidence on surgical LAA closure (LAAC) is scant.

Hypothesis:
Surgical LAAC is associated with reduced risk of mortality and stroke.

Methods:
We conducted a meta-analysis on the studies comparing the patients who underwent open-heart surgery with or without LAAC. Literature search was performed on PubMed, Embase, and Cochrane Trials databases. Outcomes of interest were 30-day/in-hospital mortality and morbidity, and late mortality and stroke. I-square statistics were used to evaluate heterogeneity and publication bias was evaluated by Begg’s and Egger’s tests.

Results:
We reviewed 821 articles and 12 articles including 7466 patients (3039 in LAAC group and 4427 in Non-LAAC group) were selected for the analysis. Among 12 studies, 3 were randomized-controlled, 2 were propensity-matched, and others were cohort study. There was no significant heterogeneity or publication bias. At 30-day/in-hospital follow-up, LAAC was not associated with risk of mortality or stroke (Risk ratio (RR) 0.67, 95% confidence interval (CI) 0.42-1.06 for mortality, and RR 0.83, 95%CI 0.54-1.26 for stroke). LAAC was not associated with risk of postoperative AF or re-exploration for bleeding. At the latest follow-up, LAAC was significantly associated with decreased risk of mortality (Risk ratio (RR) 0.64, 95%CI 0.44-0.94, p-value 0.024). This association showed similar tendency in stratified meta-analysis by age, sex, study design, type of surgery, and preoperative AF status.

Conclusions:
LAAC was associated with decreased risk of late mortality, but not late stroke. Better survival in LAAC group would be based on baseline differences or postoperative anticoagulation management. Further prospective investigation is needed to clarify these findings.
Abstract 11395: Enhanced External Counter Pulsation Improves Lipid Abnormalities in Patients With Chronic Ischemic Heart Disease
Authors: Mittal Sanjay , Jain Vivek , Bansal Manish , Kapoor Jyotsana , Kasliwal Ravi R , Trehan Naresh
Published: April 2024

Introduction:
Enhanced external counter pulsation (EECP) is effective in improving anginal symptoms in patients with ischemic heart disease (IHD); however its effect on the lipid profile has not yet been reported.

Hypothesis:
Exercise like peripheral muscle training effect of EECP could improve lipid profile.

Methods:
Two hundred and twenty nine consecutive patients, age 61.2+/-9.5 years, 207 (90.3%) males, left ventricular ejection fraction 35.5+/-11.7%, referred for EECP therapy between 2013 and 2016 were included in the study. All patients had symptomatic IHD and were on anti-ischemic and statin therapy. Patients were subjected to 35 EECP sessions of one hour each. All patients were subjected to a thorough clinical evaluation and a 12 hour fasting lipid profile estimation at the baseline and after completion of 35 sessions of EECP therapy. Concomitant medical therapy, including statins, remained unaltered during the course of EECP.

Results:
Significant improvement was noted in functional class, 6 minute hall walk test and activity scale after EECP therapy. Lipid abnormalities were common in these patients at baseline with 104 (45.4%) subjects having low density lipoprotein cholesterol (LDLC) > 70 mg/dl, 128 (55.8%) having high density lipoprotein cholesterol (HDLC) <35mg/dl and 79 (34.5%) having triglycerides >140mg/dl. EECP resulted in significant improvement in lipid parameters in these patients- LDLC decreased by 18.5% (from 95.1+/-26.7 to 77.5+/-24.3 mg/dl, P value <0.0001), triglycerides decreased by 18.9% (from 198.3+/-76.4 to 160.8+/-56.6 mg/dl, , P value <0.0001) and HDLC increased by 14.2% (from 28.1+/-5.2 to 32.1+/-9.1 mg/dl, P value <0.0001). The subgroups with worse baseline lipid levels showed larger improvement- patients having baseline LDLC >100mg/dl showed 29.6% reduction in LDLC and those with HDLC <25mg/dl showed 41.3% increase in HDLC after EECP therapy.

Conclusions:
Patients with IHD having abnormal baseline lipid levels despite statin therapy show significant improvement in LDLC, triglyceride and HDLC levels after EECP therapy. This improvement is likely to be due to the exercise like peripheral muscle training effect of EECP and needs further evaluation.
Abstract 11396: Myocardial Afadin Attenuates Chronic Pressure Overload-Induced Cardiac Damage via Transforming Growth Factor β Receptor-Mediated Signaling
Authors: Ogita Hisakazu , Zankov Dimitar P
Published: April 2024

Afadin, an adaptor protein of cell adhesion molecules nectins, plays a key role in embryonic morphogenesis and tissue organization together with or independent of nectins. However, little is understood how myocardial afadin pathophysiologically functions in the heart. In cardiomyocytes, afadin is reported to localize at the intercalated disks. We, in this study, generated conditional knockout mice lacking myocardial afadin (afadin-cKO mice) by the Cre/loxP system. The proportion of born afadin-cKO mice complied with the Mendel’s law and their appearance was undistinguishable from the littermate control mice. Heart rate, blood pressure, and cardiac dimension and contractility showed similar results between afadin-cKO and control mice. Gross heart morphology, heart weight, histology, and intercalated disks structure in afadin-cKO mice did not differ from those in control mice. We then used a model of chronic pressure overload for 8 weeks created by transverse aortic constriction (TAC) operation. This pressure overload significantly induced systolic dysfunction, enhanced fibrogenesis and apoptosis in afadin-cKO mice comparing with control mice. Myocardial afadin deletion aggravated macrophage infiltration early after TAC procedure. Loss of afadin suppressed transforming growth factor (TGF) β receptor-mediated signaling: phosphorylation of Smad2 and TAK1. Afadin was also found to interact with TGFβ receptor I at the intercalated disks, which was confirmed by co-immunoprecipitation experiments and confocal microscopy. This interaction may contribute to enhancement of TGFβ receptor-mediated signaling initiated by TAC procedure, and prevent cardiac damage. In contrast, administration of SB431542, a pharmacological antagonist of TGFβ receptor I, augmented mononuclear infiltration in the hearts of TAC-operated control mice. In conclusion, afadin is a critical molecule of cardiac protection against chronic pressure overload. The beneficial effects are likely to be a result of afadin interaction with TGFβ receptor.
Abstract 11436: Empagliflozin Early Reverses Metabolic and Cardiovascular Overload in Type-2 Diabetics With Chronic Heart Failure
Authors: Murakami Tatsuaki , Ohsato Kazuo
Published: April 2024

Introduction:
Diabetes mellitus is thought to be highly involved in complex metabolic and cardiovascular disturbances, however the effective therapies in patients with diabetes mellitus and chronic heart failure have not been established.

Hypothesis:
We assessed hypothesis that empagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, a recently developed antidiabetic agent, promptly reverses complex metabolic and cardiac disturbances in patients with type-2 diabetes mellitus and chronic heart failure.

Methods:
Type-2 diabetic patients with chronic heart failure were randomized to group-E where they received antidiabetic therapy with empagliflozin for 2 weeks, or to group-C where they received enhanced therapies with conventional antidiabetic agents without an SGLT2 inhibitor. We evaluated practical metabolic and cardiovascular variables including NT-proBNP and ultrasonic quantified diameter of inferior vena cava (IVCD). Changes in practical metabolic and cardiovascular variables were compared between the 2 groups.

Results:
The patients in group-E (n=22) manifested improvements in metabolic and cardiovascular variables represented by blood glucose (-35.3±18.2 mg/dL, p=0.02), systolic blood pressure (-7.4±1.5 mmHg, p=0.01), body weight (-1.5±0.7 kg, p=0.01), and NT-proBNP (pg/mL; from 636.3±612.8 to 433.4±437.7, p=0.03), while those in group-C (n=11) showed no improvement except for blood glucose. Heart rate remained unchanged in both groups. The changes in body weight was characterized by those in water weight as well as those in fat weight, but not by those in muscle weight. Respiratory variation in IVCD increased in group-E (%; from 50.4±7.1 to 64.2±8.8, p=0.03), while it remained unchanged in group-C. Changes of respiratory variation in IVCD or NT-proBNP in group-E did not correlate to those of blood glucose (IVCD: r=0.09, p=0.88, NT-proBNP: r=0.14, p=0.68).

Conclusions:
These results indicate that empagliflozin in diabetic patients with chronic heart failure early reverses metabolic and cardiovascular overload independent of glucose lowering, which may provide novel potential benefit for management of progressive metabolic and cardiovascular disturbances in type-2 diabetics with chronic heart failure.
Abstract 11437: Cooking Methods for Red Meat and Risk of Type 2 Diabetes in U.S. Women
Authors: Liu Gang , Zong Geng , Hu Frank B , Willett Walter , Eisenberg David M , Sun Qi
Published: April 2024

Background:
Red meat intake is an established risk factor for developing type 2 diabetes (T2D), although the role of cooking methods in the associations of red meat intake with T2D is largely unknown. This study aimed to examine red meat cooking methods in relation to risk of T2D among U.S. women who were regular meat-consumers (≥2 servings of red meat intake per week).

Methods:
We prospectively followed 59,032 women in the Nurses’ Health Study through 2012, who were free of diabetes, cardiovascular disease, and cancer at baseline in 1986. Diet was assessed by validated food-frequency questionnaires. Weekly frequency of cooking methods for red meat, including roasting, broiling, barbequing, pan-frying, and stewing or boiling, were collected at baseline.

Results:
During 1.24 million person-years of follow-up, we documented 6,205 incident T2D cases. After multivariate adjustment for demographics, lifestyle factors, and cooking methods, comparing extreme quintiles, the HR (95% CI) of T2D was 1.18 (1.07, 1.30) for total red meat intake and 1.31 (1.20, 1.43) for processed red meat intake (both
P
trend<0.001). Higher frequency of broiling and barbequing for red meat were associated with greater weight gain over 8 years (all
P
<0.05). After multivariate adjustment including total red meat intake, and comparing with cooking red meat <1 time/month, participants cooking red meat
≥
2 times/week had an HR (95% CI) of T2D that was 1.28 (1.18, 1.39) for broiling (
P
trend<0.001), 1.22 (1.10, 1.36) for barbequing (
P
trend<0.001), 1.10 (1.00, 1.22) for roasting (
P
trend=0.17), 0.84 (0.76, 0.93) for pan-frying (
P
trend=0.01), and 0.97 (0.85, 1.09) for stewing or boiling (
P
trend=0.97). When cooking methods were further mutually adjusted, the results remained similar.

Conclusion:
These findings suggested that, beyond the risk of red meat intake, high-temperature open-flame cooking methods for red meat, especially broiling and barbequing, are independently associated with a higher risk of T2D.
Abstract 11779: Third Generation Cryoballoon Facilitates Time-to-Isolation Dependent Freeze Protocols
Authors: Petscher Kerstin , Pott Alexander , Rottbauer Wolfgang , Dahme Tillman
Published: April 2024

The introduction of the 2
nd
generation cryoballoon (Medtronic Arctic Front Advance, AFA) increased efficacy of cryoballoon pulmonary vein (PV) isolation. Real time monitoring of the time-to-isolation (TTI) with a diagnostic spiral mapping catheter introduced through the cryoballoon inner lumen has emerged as a valuable parameter to estimate the quality of the ablation lesion. A short TTI appears to be predictive of a durable isolation, whereas a long TTI is linked to increased risk of PV reconnection. Real-time recording of TTI is limited in AFA due to a long distal tip of the balloon, which often inhibits registration of PV signals. A modification of the balloon design with a shorter tip (Medtronic Arctic Front Advance ST, AFA-ST) is supposed to facilitate registration of PV signals during isolation, because the spiral mapping catheter can be placed within the muscular sleeve of the PV. We have compared PV isolations with either the AFA-ST or the AFA cryoballoon and have implemented a protocol in the AFA-ST group depending on the observed TTI: In case of TTI <30s the freeze-cycle was reduced to 120s, in case of TTI of 30s or more the freeze cycle was set to 180s. If TTI was more than 60s we added a 180s bonus freeze. In contrast, in the AFA group all PVs were isolated by an initial freeze cycle of 240s followed by a 240s bonus freeze. We included 74 patients in this non-randomized case-control trial, with 37 patients in each group. In each group we identified 149 PVs. All PVs were isolated successfully. Mean procedure duration was 107 ±19 min in the AFA group and 85 ±20 min in the AFA-ST group (p<0.001). In the AFA group we registered a TTI in 83 PVs (55.7%), whereas TTI was documented in 122 PVs (81.9%) in the AFA-ST group (p<0.001). Mean TTI was 44 ±25s in the AFA group and 42 ±22 s in the AFA-ST group (p=0.25). Patients were followed-up for an average period of 6.2 ±2.9 months. The Kaplan-Meier estimated freedom from atrial arrhythmia recurrence 6 months after the procedure was 88.9% in the AFA group and 81.6% in AFA-ST group (p=0.300). In conclusion, we here demonstrate, that registration of TTI occurs significantly more frequent with the new AFA-ST cryoballoon. Thus tailoring of freeze cycle duration is feasible and leads to comparable clinical outcomes to standard fixed freeze cycles.
Abstract 11818: Post-shock Pacing With the Subcutaneous Implantable Cardioverter-Defibrillator (S-ICD): Results From the IDE Trial
Authors: Verma Nishant , Prutkin Jordan M , Patton Kristen K , Burke Martin C , Weiss Raul , Weiss Raul , Knight Bradley P
Published: April 2024

Introduction:
In the subcutaneous implantable cardioverter-defibrillator (S-ICD) system, post-shock pacing (PSP) is a programmable feature allowing the delivery of 200 mA of transthoracic demand ventricular pacing at 50 bpm for up to 30 seconds post-shock. The need for and efficacy of PSP with the S-ICD is unknown.

Methods:
The S-ICD Investigational Device Exemption (IDE) trial enrolled 330 patients, 314 of whom underwent successful S-ICD implantation. At the time of implant, VT/VF was induced with a transthoracic 50Hz burst during testing and again ≥150 days later if the patient was also enrolled in a chronic conversion testing study. PSP was enabled at the discretion of the investigator. Regardless of the vector selected for VT/VF sensing, PSP sensing is based on the vector between the parasternal electrodes rather than a vector including the generator as it is part of the pacing bipole and unable to sense. Capture was defined as the presence of a QRS complex immediately after the pacing stimuli.

Results:
PSP was enabled for 728 of the 733 VT/VF episodes during conversion testing. Of these, 654 were at initial implant and 74 at chronic conversion testing. In 544 episodes (74.8%), PSP was appropriately inhibited as the heart rate was >50 bpm. In 184 episodes (25.2%) there was at least one paced beat post-shock. In one episode, a single impulse of PSP was inappropriately delivered when an ectopic beat was undersensed. PSP occurred with equal frequency at acute (25.4%) and chronic (24.3%) conversion testing. In all episodes, capture was achieved when pacing was delivered. There were no pacing-induced arrhythmias, undersensing of VT/VF recurrence despite the change in sensing vector or other harm associated with PSP.

Conclusion:
Transthoracic demand ventricular PSP is safely and effectively delivered by the S-ICD for up to 30 seconds in approximately one quarter of subjects for a heart rate ≤ 50 bpm immediately after an effective shock for induced VT/VF. Since shocks were delivered in the presence of deep sedation or general anesthesia, how this correlates with the need for pacing and its tolerability after shocks for spontaneous events remains unknown.
Abstract 11908: Organizational Structure, Resources, and Educational Initiatives in Cardiac Intensive Care Units: A National Cross-sectional Survey on Behalf of the American Heart Association Acute Cardiac Care Committee
Authors: Fordyce Christopher B , Wegermann Zachary , Granger Christopher B , Stebbins Amanda , Morrow David A , Henry Timothy D , Gilchrist Ian C , Katz Jason N , Cohen Mauricio G , Newby L. K , Van Diepen Sean
Published: April 2024

Introduction:
The acuity and medical complexity of patients admitted to cardiac intensive care units (CICUs) is increasing; yet, little is known about contemporary CICU organizational structures, staffing, resources, and educational activities in the United States

Methods:
A cross-sectional, 16-question web-based survey was distributed electronically (October 2015) to AHA Mission: Lifeline coordinators at 542 registered hospitals with a request for completion by the CICU director or unit manager. Non-responders were contacted by email and phone.

Results:
A total of 138 hospitals (25.5% response rate) had completed the survey by May 1, 2016 (17.4% academic, 20.3% tertiary non-academic, and 62.3% community hospitals). Most CICUs were open units (76.8%) with multiple simultaneous responsible attending physicians. The Figure shows variation in CICU patient populations, organizational structure, medical leadership and role of intensivists. Overall, 61% of centers participated in clinical training of housestaff and/or advanced practice providers, while only 8.5% of centers had a dedicated Cardiac Critical Care subspecialty training program. 12.3% of all CICUs had the organizational structure and on-site resources to be classified as a Level 1 CICU by 2012 American Heart Association Scientific Statement on CICU medical staffing and training models.

Conclusions:
Among US hospitals, there was substantial variability in CICU organizational structure, practice, and educational activities. Approximately 1 in 10 CCUs had on-site resources necessary matching a Level 1 CICU classification. These data inform the current CICU landscape and may help to identify potential areas for organizational improvement and resource allocation.
Abstract 11918: Lipoprotein(a) Predicts Subclinical Atherosclerosis in HIV-infected Young Women in the Women’s Interagency HIV Study
Authors: Enkhmaa Byambaa , Anuurad Erdembileg , Zhang Wei , Li Chin-Shang , Kaplan Robert , Lazar Jason , Merenstein Dan , Karim Roksana , Aouizerat Brad , Cohen Mardge , Butler Kenneth , Pahwa Savita , Ofotokun Igho , Adimora Adaora A , Golub Elizabeth , Berglund Lars
Published: April 2024

Background/Objectives:
Lipoprotein(a), Lp(a), is an independent causal risk factor for cardiovascular disease (CVD), where levels are regulated by the apolipoprotein(a), apo(a), gene. HIV-infected individuals are at significantly elevated CVD risk compared to HIV-uninfected individuals. The role of Lp(a) in HIV-related CVD remains unclear. We investigated the association between Lp(a) level, apo(a) size polymorphism and subclinical atherosclerosis in HIV-infected and HIV-uninfected women in the Women’s Interagency HIV Study.

Methods:
Lp(a) level, apo(a) size polymorphism and common carotid artery intima-media thickness (cIMT) were determined in 150 HIV-infected and 100 HIV-uninfected women. Lp(a) levels were square-root transformed to achieve normality. Linear regression models were used to evaluate the association of Lp(a) with cIMT adjusting for confounders.

Results:
The mean ages for the HIV+ and HIV- groups were 31 ± 4 and 30 ± 4 years, respectively. The majority of women were African-Americans (69% and 76% in the HIV+ and HIV- group, respectively). HDL-cholesterol, triglyceride and Lp(a) levels were significantly lower in the HIV+ vs. HIV- group. Prevalence of atherogenic small size apo(a) (<22 Kringles) was ~20% in both groups. Notably, Lp(a) level was predictive of cIMT in the HIV+ group [β = 0.00541, 95% CI = (0.000608, 0.010212),
p
=0.029], but not in the HIV- group [β = 0.00175, 95% CI = (-0.0045024, 0.0080024),
p
=0.584]. After accounting for confounders (age, race, smoking, BMI, blood pressure, HCV co-infection, menopause, blood lipids, treatment status, CD4+ T-cell count, and HIV/RNA viral load), the association remained significant [β = 0.00532, 95% CI = (0.0000672, 0.0105728),
p
=0.049] in the HIV+ group.

Conclusions:
Lp(a) level is associated with subclinical atherosclerosis in young HIV-infected women. Further research is needed to identify mechanisms underlying Lp(a)-associated increased CVD risk in HIV-infected individuals.
Abstract 11924: Prevalence and Predictors of End-of-Life Discussions in Patients Hospitalized With Acute Decompensated Heart Failure
Authors: Young Kathleen A , Strand Jacob J , Redfield Margaret M , Dunlay Shannon M
Published: April 2024

Introduction:
Although national guidelines call on physicians to conduct regular conversations about end-of-life (EOL) care and planning with patients with heart failure (HF), research suggests that physicians often avoid these discussions. The aim of this study was to evaluate whether patients hospitalized with acute decompensated HF (ADHF) reported ever discussing their preferences for EOL care with their physicians.

Methods:
Between January 2014 and January 2016, Southeastern Minnesota residents hospitalized with ADHF at Mayo Clinic hospitals in Rochester, MN were prospectively recruited into an observational cohort study that included the administration of face-to-face questionnaires. Patients were asked questions regarding details of EOL discussions with their physicians, their preference for prognostic information, whether they had an advanced directive, attitudes about dying and hospice, and familiarity with palliative care and hospice.

Results:
Among 400 patients (mean age 77.7 years, 46% female, 48% preserved ejection fraction), only 68 (17.5%) reported previously discussing EOL wishes with their physician. Most patients (62.2%) indicated a preference to discuss their prognosis with their physician. Patients reporting prior EOL discussions were more often anemic (82.6% vs. 68.9%, p=0.022), hyponatremic (28.6% vs. 12.5%, p=0.002), and married (68.1% vs. 51.5%, p=0.012). They more often recognized the term ‘hospice’ (95.7% vs. 87.3%, p=0.045), had more favorable attitudes of dying and hospice (p=0.030), and more often had an advanced directive (83.6% vs. 67.7%, p=0.010). No other differences in demographics, comorbidity burden, HF characteristics, or in-hospital and 30-day outcomes were observed.

Conclusions:
Only 17.5% of patients hospitalized with ADHF reported previously discussing their preferences for EOL care with their physician. Patients reporting EOL discussions were more knowledgeable about EOL options and more likely to have completed advance care planning documents. Despite increasing recognition of the importance of these conversations, they are still occurring infrequently, and represent an important modifiable gap in the optimal longitudinal care of patients with HF.
Abstract 11973: Decrease In Mortality Rate And Hospital Admissions For Acute Myocardial Infarction After The Enactment Of The Smoking Ban Law In Sao Paulo City
Authors: Ogawa Tania
Published: April 2024

Introduction:
Smoking restriction laws have been spread over the world in the last decade. Previous studies and meta-analyses showed a decline in the community rates of myocardial infarction and/or heart attack after enactment of these laws. However, there are few data about the Latin American population. In the first phase of this study, we reported a well succeed implementation of the law in Sao Paulo city, with decrease in carbon monoxide rates in places like restaurants, bars and night clubs.

Hypothesis:
To evaluate whether the 2009 implementation of a smoking ban law in Sao Paulo city was associated with reduction in rates of mortality and hospital admissions for myocardial infarction.

Methods:
We performed a time series study of monthly rates of mortality and hospital admissions for acute myocardial infarction from January 2005 to December 2010. The data derived from DATASUS, the main public health information system existent in Brazil and from SIM (Mortality Information System). Adjustments and analysis were done using Autoregressive Integrated Moving Average with exogenous variables (ARIMAX) method modeled by environmental variables and atmospheric pollutants to evaluate the tendency of mortality and hospital admissions before the law and forecast events after the law. We also used Interrupted Time Series Analysis (ITSA) associated to ARIMAX to compare the period before the law, the moment of implementation of the law and the period after the law.

Results:
We observed a reduction in the hospital admissions (-5,4% in the first 2 months after the law) and mortality rate (-11,9% in the first 17 months after the law) for myocardial infarction.

Conclusions:
Hospital admissions and mortality rate for myocardial infarction were reduced in the first months after smoking ban law.

Graphic 1: Hospital admission rate for myocardial infarction, São Paulo city, 2005 to 2010.

Graphic 2: Mortality rate for myocardial infarction, São Paulo city, 2005 to 2010.