bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9636: Autophagy Plays a Critical Role in Maintenance of Cardiac Function in Diabetes
Authors: Kanamori Hiromitsu , Takemura Genzou , Goto Kazuko , Tsujimoto Akiko , Mikami Atsushi , Ogino Atsushi , Watanabe Takatomo , Morishita Kentaro , Seishima Mitsuru , Minatoguchi Shinya
Published: April 2024

Although diabetic cardiomyopathy, which develops in the absence of major coronary artery disease, is one of the leading causes of heart failure, the pathogenesis is still unclear. Little is known on the relationship between diabetic cardiomyopathy and autophagy which is intracellular self digesting mechanism and reported in various pathologic conditions. Here, we investigated the perturbation of autophagy in diabetic hearts. We used GFP (green fluorescent protein)-LC3 (microtubule-associated protein 1 light chain 3) transgenic mice to monitor the autophagic vacuole in which type I diabetes was induced by an intraperitoneal injection of streptozotocin (250 mg/kg). Thirty-four diabetes mice were treated with saline or an autophagy inhibitor chloroquine (10mg/kg/day) (n=17 each) for 2 weeks while so were nondiabetes control group (n=17 each). Cardiac function was evaluated by echocardiography and cardiac catheterization. In diabetes mice, although systolic cardiac function and left ventricular diameter were similar to nondiabetes mice, diastolic cardiac function was aggravated compared with nondiabetes mice. And autophagic findings were significantly augmented in diabetes heart where expression levels of LC3-II, LC3-II/I ratio, p62, and cathepsin D were increased and abundant autophagic vacuoles and lysosome were observed under electron microscopy. The AMP-activated protein kinase (AMPK) was upregulated and myocardial ATP content was decreased in diabetes heart. Treatment with chloroquine provided no significant influence on the cardiac function and geometry in nondiabetes mice. In diabetes mice, however, chloroquine treatment caused significant left ventricular dilatation and aggravation of cardiac function (both systolic and diastolic), in which autohagic findings were significantly suppressed. In addition, chloroquine treatment brought about further reduction of ATP content and further activation of AMPK in the diabetes heart. In conclusion, our findings suggest a critical role of autophagy that compensates for lack of energy to maintain cardiac function in diabetes heart.
Abstract 9671: Molecular Dynamics and Calcium Binding Studies on Troponin Mutations Causing Dilated Cardiomyopathy
Authors: Lindert Steffen , McCammon Andy
Published: April 2024

Troponin (Tn), part of the thin filament in cardiomyocytes, plays an important role in calcium signaling events in cardiac muscle contraction. It acts as a Ca2+-dependent switch, activating and deactivating the myofilament leading to contraction and relaxation of the muscle cell. The most common form of heart muscle disease, dilated cardiomyopathy (DCM), is characterized by dilatation of the heart and impaired systolic function of the left or both ventricles. Several Tn mutations that cause DCM have been reported. We used microsecond timescale molecular dynamics (MD) simulations to elucidate the molecular action of three troponin C (TnC) DCM mutations - D75Y, E59D and G159D - with particular focus on calculating the free energy difference between the open and closed states of the TnC as well as average times between opening events. We found free energy differences between the open and closed states of ~8 kcal/mol for the wildtype system. While G159D causes a significant increase in the free energy difference (by ~4 kcal/mol), D75Y does not change the free energy difference significantly, and E59D even causes a ~2 kcal/mol drop in the free energy difference. This finding illustrates nicely that the opening propensity of the TnC hydrophobic patch is only one possible mechanism by which DCM mutations can influence the contractility in cardiomyocytes. Both G159D and E59D use this mechanism. D75Y, however, does not influence TnI binding but rather impacts Ca2+-binding affinity, which can also be observed in our Brownian Dynamics simulations of calcium association.
Abstract 9683: Leisure-time Physical Inactivity and Risk of Myocardial Infarction and All-cause Mortality: a Case-control Study
Authors: Calais Fredrik , Fröbert Ole , Rosenblad Andreas , Hedberg Pär O , Wachtell Kristian , Leppert Jerzy
Published: April 2024

Background:
Physical inactivity has pandemic qualities, with major impacts on cardiovascular morbidity and death. However, it is unclear whether the association is affected by extra-cardiac atherosclerotic disease (EAD) and in what ways physical inactivity before myocardial infarction (MI) affects post-MI prognosis. Our hypothesis is that leisure time physical inactivity (LTPI) is an important independent risk factor for MI, and that a sedentary lifestyle is associated with a less favorable outcome after MI.

Methods and results:
The study included patients (n=734) with acute myocardial infarction (MI), and, for each patient, an age, gender, and city-of-residence matched control with no history of MI. Baseline physical activity level was compared between patients and controls and results were adjusted for medical history and clinical data including objective measures of EAD. All-cause mortality in both patients and controls during the course of the study was stratified according to level of physical activity
:
Leisure time physical inactivity was associated with a more than 2-fold risk of MI [unadjusted odds ratio (OR) 3.4, 95% confidence interval (CI) 2.59-4.45,
P
<0.001, adjusted OR 2.1, CI 1.45-2.91,
P
<0.001]. Survival at 6 years for LTPI vs. active patients was 70% vs. 90% (
P
<0.001) and for LTPI vs. active controls 81% vs. 95% (
P
=0.002). The unadjusted risk of death from all causes during follow-up was significantly higher in the LTPI group compared to the active group both for patients [hazard ratio (HR) 3.9, CI 2.57-6.01,
P
<0.001], and controls (unadjusted HR 3.3, CI 1.46-7.34,
P
=0.004). After adjustment the HR remained significantly elevated for patients (HR 2.3, CI 1.48-3.73,
P
<0.001) but not for controls (HR 1.7, CI 0.66-4.26,
P
=0.27).

Conclusion:
Leisure time physical inactivity is independently associated with MI and death after MI.
Abstract 9783: Echocardiographic Normalization in Children With Idiopathic Dilated Cardiomyopathy: Results From the Pediatric Cardiomyopathy Registry
Authors: Everitt Melanie D , Sleeper Lynn A , Lu Minmin , Canter Charles , Pahl Elfriede , Wilkinson James D , Addonizio Linda J , Towbin Jeffrey A , Rossano Joseph , Singh Rakesh K , Lamour Jacqueline , Webber Steve A , Colan Steven D , Margossian Renee , Kantor Paul F , Jefferies John L , Lipshultz Steven E ,   For the PCMR Investigators
Published: April 2024

Background:
Children with idiopathic dilated cardiomyopathy (IDCM) commonly have a poor outcome; however, some improve with normalization of ventricular size and systolic function at follow-up. The incidence of and predictors for such normalization are largely unknown.

Methods:
All children age ≤18 years with IDCM who had both depressed left ventricular (LV) function (FS or EF z-score<-2) and LV dilation (end diastolic dimension [LVEDD] z-score>2) on the first echo were identified. At least 1 follow-up echo within 2 years of diagnosis was required for inclusion. Competing risks methodology was used to estimate cumulative incidence and predictors for normalization (FS/EF z-score>-2 and LVEDD z-score<2) within 2 yrs of diagnosis.

Results:
Among 1387 children with IDCM enrolled from 1990-2009 in the Pediatric Cardiomyopathy Registry (PCMR), 868 (63%) met inclusion criteria of depressed LV function and dilation. Of these, 773 (89%) had echo follow-up and were included for analysis. Echo normalization occurred in 25% by 2 yrs, at a median of 9.4 months. Fig. 1 shows cumulative incidence of the following competing outcomes: (1) normalization; (2) death or transplantation (51% by 2 yr); and (3) persistently abnormal echo (24% by 2 yr). Younger age (RR:0.90, 95% CI:0.86-0.94, p<0.001) and lower LVEDD z-score (RR:0.74, 95% CI:0.66-0.82, p<0.001) were independent predictors for normalization. Nine patients (9%), who had echo normalization within 2 yrs of diagnosis, later deteriorated and underwent heart transplant or died.

Conclusions:
Echo normalization of LV size and systolic function occurred by 2 yrs in 25% of children with IDCM in this large multi-site registry. Younger children and those with less LV dilation at presentation were more likely to normalize. Continued follow-up of children with echo normalization after IDCM is warranted since a subset of these children had subsequent deterioration leading to death or transplantation.
Abstract 9790: Central Venous Pressure After Coronary Artery Bypass Surgery: Does it Predict Postoperative Mortality or Renal Failure?
Authors: Williams Judson B , Peterson Eric D , Wojdyla Daniel , Southerland Kevin W , Ferguson T. Bruce , Smith Peter K , Milano Carmelo A , Lopes Renato D
Published: April 2024

Background:
While hemodynamic monitoring is often performed following coronary artery bypass grafting (CABG), the role of monitoring postoperative central venous pressure (CVP) measurement as a predictor of clinical outcomes is unknown.

Methods:
Detailed clinical data were analyzed from 2,390 randomly selected patients undergoing high risk CABG or CABG/valve at 55 hospitals participating in the Society of Thoracic Surgeons’ National Cardiac Surgery Database from 2004 to 2005. Eligible patients underwent elective/urgent isolated CABG with an ejection fraction < 40%, or elective/urgent CABG at age ≥65 years with diabetes or a glomerular filtration rate 60 mL/min per 1.73 m
2
. Correlation between post-operative CVP and in-hospital / 30-day mortality and renal failure was assessed as a continuous variable, both unadjusted and after adjusting for important clinical factors using logistic regression modeling.

Results:
Mean age was 72 years, 54% of patients had diabetes mellitus, 49% were urgent procedures, and mean cardiopulmonary bypass time was 105 minutes. Patients’ CVP 6 hours post-operation was strongly associated with in-hospital and 30 day mortality: odds ratio (OR) 1.5 (95% confidence interval [CI] 1.23, 1.87) for every 5 mmHg increase in CVP, p<0.0001. This association remained significant after risk-adjustment for cardiac index: adjusted OR 1.44 (95% CI 1.10, 1.89), p<0.01. A model adjusting for cardiac index also revealed increased incidence of mortality or renal failure: adjusted OR 1.5 (95% CI 1.28, 1.86) for every 5 mmHg increase in CVP, p<0.0001.

Conclusion:
Patients’ central venous pressure at 6 hours following CABG surgery was highly predictive of operative mortality or renal failure, independent of cardiac index and other important clinical variables. Future studies will need to assess whether interventions guided by post-operative CVP can improve patient outcomes.
Abstract 9815: Loss of Inhibitory Fcgamma Receptor II is not Sufficient to Promote Atherosclerosis in Hyperlipidemic Apoe Knockout Mice
Authors: Zhu Xinmei , Ng Hangpong , Nagarajan Shanmugam
Published: April 2024

Hypothesis:
Elevated anti-oxidized LDL IgG and its interaction with Fcgamma receptors (FcR) have been suggested to be associated with the progression of atherosclerosis. Four different classes of FcRs, FcRI, FcRII, FcRIII, and FcRIV, have been characterized in mice. Functionally, FcRs can be classified into the activating (FcRI, III, and IV) and inhibitory (FcRII) receptors. Previous finding from our lab and others have shown that deletion of activating Fcgamma receptors (I, III and IV) in apoE KO mice decreased atherosclerosis. This led to our hypothesis that deficiency of inhibitory FcRII exacerbates atherosclerosis.

Methods and Results:
We tested this hypothesis using apoE-FcRIIb double knockout (congenic to C57BL/6, FcRIIb
B6
) mice. On the contrary to our hypothesis, compared to apoE KO mice apoE-FcRIIb double knockout mice (FcRIIb
B6
) fed chow or high-fat diets did not show exacerbated atherosclerotic lesions (n=10/group). Our finding is in contrast to previous reports showing exacerbated lesions in apoE-FcRIIb mice in a mixed background (129s/v and C57BL/6, FcRIIb
mixed
). Molecular mechanisms to understand the difference revealed that FcRIIb
mixed
mice showed more Th1 response (more IFN-gamma, TNF-alpha), while congenic FcRIIb
B6
showed predominant Th2 responses (more IL-10, IL5, and IL-13). Moreover, anti-oxLDL IgG subtypes analyses showed elevated mIgG2a (Th1) response in FcRIIb
mixed
mice, while mIgG1 (Th2) levels were more predominant in FcRIIb
B6
mice. Interestingly, circulating levels of autoantibodies, anti-nuclear antibodies, which have been implicated in autoimmune diseases such as lupus also was elevated in FcRIIb
mixed
compared to FcRIIb
B6
mice.

Conclusion:
These findings revealed a novel paradigm that inhibitory FcRIIb does not directly contribute to atherosclerosis. However, in the presence of lupus susceptible gene loci, inhibitory FcRIIb exacerbates the progression of atherosclerosis. As FcRIIb polymorphism has been implicated in lupus susceptibility, the role of FcRIIb, as pro-atherosclerotic mediators in vivo in lupus-associated cardiovascular disease need to be investigated.
Abstract 9819: Elevated Plasma Serotonin and Endothelin-1 in Coronary Artery Disease Patients: A Potential for Novel Pharmacotherapeutic Targets?
Authors: Shousha Sherif , Diodati Jean G , Schampaert Erick , Pharand Chantal
Published: April 2024

Background:
High on-treatment platelet reactivity (HTPR) was reported in patients with coronary artery disease (CAD) on dual antiplatelet therapy with aspirin and clopidogrel, particularly in diabetic patients. We sought to investigate the potential for targeting platelet and endothelium-derived vasoactive substances (such as thromboxane A
2
[TXA
2
], serotonin [5-HT], and endothelin-1 [ET-1]) released upon platelet activation to complement current antiplatelet therapy without increasing the risk of bleeding.

Methods:
Three groups of subjects were recruited: a) 20 diabetic patients with known CAD (DM), b) 24 non-diabetic patients with known CAD (ND) and c) 27 healthy subjects without diabetes or CAD (CTL). Subject groups were compared to each other with respect to plasma and platelet concentrations of various vasoactive substances measured by ELISA and to platelet reactivity measured by light transmission aggregometry (LTA) and VerifyNow
®
.

Results:
Significantly higher ET-1 (CTL: 0.372 0.1 pg/mL; ND: 0.564 ± 0.2 pg/mL, P<0.005 vs. CTL; DM: 0.961 ± 0.2 pg/mL, P<0.02 vs. CTL) and 5-HT (CTL: 600.5 ± 52.5 ng/mL; ND: 679.6 ± 68.7 ng/mL, P<0.05 vs. CTL; DM: 729.7 ± 81.8 pg/mL, P<0.02 vs. CTL) plasma concentrations were found in CAD patients, with a more pronounced increase in the DM group. Platelet 5-HT was lower in the DM group (335.8 ± 71 ng/10
9
platelets) compared to both CTL subjects (447.1 ± 88.5 ng/10
9
platelets) and ND patients (374.6 ± 58.8 ng/10
9
platelets), which may be due to increased platelet activation and release. Plasma TXB
2
concentrations were higher in the DM group (557.4 ± 172.4 pg/mL) compared to the ND group (350.7 ± 42.4 pg/mL), which indicates higher platelet reactivity in DM patients despite the regular use of ASA. Platelet function tests such as VerifyNow
®
(ASA) and LTA (AA 1.6 mM) showed higher HTPR in DM patients (VerifyNow
®
: 445 ± 29.1 ARU; LTA: 16.78 ± 3.9% aggregation) compared to ND patients (VerifyNow®: 419.1 ± 13.4 ARU; LTA: 3.76 ± 0.8% aggregation).

Conclusion:
This study identifies ET-1 and 5-HT as new potential pharmacological targets in the platelet activation pathway for management of HTPR in CAD patients to reduce the risk of incidence and recurrence of ischemic events.
Abstract 9872: Prognostic Factors of Endovascular Treatment for Femoropopliteal Lesion With Self-expandable Nitinol Stent Longer Than 300mm
Authors: Suematsu Nobuhiro , Soga Yoshimitsu , Takahara Mitsuyoshi , Iida Osamu , Suzuki Kenji , Hirano Keisuke , Kawasaki Daizo , Shintani Yoshiaki , Yamaoka Terutoshi , Tsuchiya Taketsugu
Published: April 2024

Purpose:
As technical development of catheter devices has progressed, endovascular treatments (EVT) for femoropopliteal (FP) lesions have been increasingly employed in patients with peripheral arterial disease (PAD). In the new era of drug eluting stents, the long term patency of EVT for FP lesions are improving, but there are still obstacles in the treatment of complex lesions such as TASC II D, in terms of the long term patency.

In order to clarify the prognostic factors of EVT for an extremely long FP lesion, we have retrospectively analyzed clinical data of patients receiving stents with total length >300mm for de novo FP lesions.

Methods:
A total of 296 de novo FP lesions which were treated by EVT with self-expandable nitinol bare metal stents with a total length greater than 300mm at 13 hospitals in Japan between January 2004 and December 2011 were retrospectively analyzed.

Results:
Average patient age was 73.9 years (range 50 to 93), and 180 (68.4%) were male. 157 (59.7%) had diabetes mellitus, and 44 (16.7%) were maintained on hemodialysis. 73 (27.8%) were active smokers and 91 (34.6%) were categorized to Rutherford 4, 5, or 6. All lesions were treated with self-expandable bare metal nitinol stents. Average lesion length was 266.3mm and 3.31 stents (range 1 to 6) were deployed, with average total stent length 318.0mm. During the follow-up period (mean 792.9 days), 42 patients died, of which 35.7% were due to cardiovascular disease. Primary patency rates at 1, 3, and 5 years after treatment, respectively, were 68.4%, 47.8%, and 39.1%, and secondary patency rates were 89.5%, 79.4%, and 74.0%. COX proportional hazard regression analyses revealed that male (0.47 [0.31-0.69], p<0.01), chronic total occlusion (2.19[1.05-4.56], p<0.05), calcified lesions (1.52 [1.01-2.30], p<0.05), cilostazol administration (0.60 [0.42-0.88], p<0.01), and stent fracture (2.26 [1.28-3.98], p<0.01), were significant predictors for primary patency.

Conclusion:
Even though mid-term primary patency rates of EVT for extremely long FP lesions were needed to be improved, secondary patency rates were mostly acceptable. These data will help guide proper treatment strategies for revascularization of complex FP lesions.
Abstract 9885: Pericardial Fat is Associated With Atrial Electrical Function: The Framingham Heart Study
Authors: Friedman Daniel J , Wang Na , Meigs James B , Hoffmann Udo , Massaro Joseph M , Fox Caroline S , Magnani Jared W
Published: April 2024

Background:
Obesity is a significant risk factor for atrial fibrillation (AF). Pericardial fat (Pfat) - unique for having direct myocardial contact - has been associated with AF. We hypothesized that Pfat is significantly related to atrial electrical function (AEF) as quantified by P wave indices (PWI), intermediate endophenotypes of AF risk.

Methods:
We performed a cross-sectional analysis of 1,946 Framingham Heart Study participants (45% female) to assess the relations between Pfat and AEF measured by PWI: PR interval, P wave duration (Pdur), P wave amplitude (Pamp), P wave area (Parea), and P wave terminal force (Pterm). We performed sex stratified, multivariable linear regression analyses adjusting for age, heart rate, blood pressure, AV nodal medications, hormone replacement therapy, hypertension, diabetes, and menopausal status in women, followed by adjustment for ectopic fat depots in secondary analyses.

Results:
We determined that a 1-SD increase in Pfat was significantly associated with PWI magnitude: PR interval (β=1.67, p=0.049), Pdur (β=2.32, p<0.001), and Pterm (β=297, p<0.001) among women; and Pdur (β=1.19, p=0.002), Pamp (β=-2.51, p<0.001), and Pterm (β=160, p=0.002) among men. We constructed sex-stratified restricted cubic splines to assess the relation between Pfat and Pdur (
1a)
and Pterm (
1b):
Among both sexes, Pfat was significantly associated with Pdur in models additionally adjusting for visceral fat or intrathoracic fat; a similar trend existed with Pterm. Among women, Pfat was significantly associated with Parea after adjustment for visceral and intrathoracic fat.

Conclusions:
Pfat is associated with altered AEF quantified by PWI, and the associations are independent of thoracic and visceral fat. These findings suggest altered AEF may be an intermediate step in the relation of Pfat and AF.
Abstract 9898: Aldosterone, Cardiorenal and Metabolic Disease in a General Community in Olmsted County, Minnesota: Biomarker and/or Mediator
Authors: Buglioni Alessia , Cannone Valentina , Cataliotti Alessandro , Heublein Denise M , Scott Christopher G , Bailey Kent R , Rodeheffer Richard J , Sarzani Riccardo , Burnett, Jr John C
Published: April 2024

Introduction:
Aldosterone (Aldo) increases sodium and water reabsorption and mediates inflammatory processes. Its relationship to co-morbidities has not been well defined in the general population.

Hypothesis:
We addressed the hypothesis that plasma aldosterone concentration (PAC) is associated with metabolic and cardiorenal diseases in the general community.

Methods:
We determined PAC in a general community-based cohort from Olmsted County, MN (n=1,674), and defined correlations with cardiorenal, metabolic diseases and myocardial function and structure.

Results:
PAC was detected in all subjects and ranged from 2.5 to 91 ng/dl (mean value 6.7 ng/dl, +/- SD 6.6). Multivariate analysis adjusted for age, gender, BMI, ANP and BNP showed highly significant correlations between PAC and hypertension (HTN) (p<.0001, OR=2.28, CI:1.91-2.71), atrial fibrillation (p<.01), chronic kidney disease (CKD) (p<.0001, OR=1.64, CI:1.33-2.02), central obesity (p<.0001, OR=1.61, CI:1.27-2.05), hypertriglyceridemia (p<.003), prevalence of metabolic syndrome (MetS) (p<.0007, OR=1.40, CI=1.15-1.71), obesity (p<.0001, OR=1.48, CI:1.27-1.73), and concentric left ventricular hypertrophy (cLVH) (p=.01). Recognizing that ANP and BNP are known inhibitors of Aldo, we defined the relationship between these cardiac hormones (NTpro-ANP and NT-proBNP) and PAC and observed highly significant inverse relationships with NTpro-ANP (p=0.0009), NTpro-BNP (p=0.0003) in the general population.

Conclusions:
In conclusion, in the general community, PAC is strongly correlated with renal, metabolic and cardiovascular diseases as well as cardiac remodeling. Specifically, increasing PAC is strongly associated with HTN, CKD, obesity, MetS, cLVH, and lower levels of natriuretic peptides. Our data suggest a key role of Aldo as a possible biomarker and/or mediator of human cardiorenal and metabolic diseases even in the general adult population, prior to overt disease. This study also supports a possible counter regulatory relationship between cardiac natriuretic peptides and PAC. Further studies are warranted to evaluate possible therapeutic interventions targeting Aldo as a strategy to delay disease progression.
Abstract 99: Estimated Regional Oxy-hemoglobin Concentration is an Excellent and Simple Predictor of Neurological Outcome for Post Cardiac Arrest Syndrome: A Prospective Multicenter Observational Study
Authors: Hayashida Kei , Ito Noritoshi , Nishiyama Kei , Suzuki Masaru , Tamura Tomoyoshi , Kawakami Masashi , Arimoto Hideki , Unoki Takashi , Orita Tomohiko , Murai Akira , Endo Tomoyuki , Norimoto Kazunobu , Anan Hideaki , Masubuchi Masanori , Yasuda Hideto , Nishi Yutaro , Hori Shingo ,   J-POP registry investigators
Published: April 2024

Background:
We previously reported that an regional cerebral oxygen saturation (rSO2) at hospital arrival can predict neurological outcomes in patients who suffered out-of-hospital cardiac arrest. In this post-hoc analyses, we investigated whether estimated regional oxy-Hb (erHbO2), the product of Hb and rSO2 which might represent regional tissue oxy-Hb existence theoretically, plays pivotal role in the development of neurological impairment in patients with post cardiac arrest patients (PCAS).

Methods & Results:
From May 2011 through July 2012, 363 consecutive comatose survivors admitted to hospitals were analyzed in this study. The primary outcome measure was a neurological outcome at 90 days. Forty-five patients (12.4%) presented good neurological outcome. The receiver operating characteristic curve analyses revealed rSO2 cutoff of 40% and erHbO2 cutoff of 3.6 had the maximum joint sensitivity and specificity to predict a good neurological outcome (rSO2: AUCs, 0.831; 95%CI, 0.770-0.892; sensitivity, 84.4%; specificity, 76.1%. erHbO2: AUCs, 0.872; 95%CI, 0.821-0.923; sensitivity, 91.1%; specificity, 71.4%). In a subgroup of patients with rSO2 >40% of optimal cutoff (n=114, 38 [33.3%] patients with good outcome), multivariate analysis revealed that erHbO2 was a significant predictor of a good neurological outcome (Odds: 1.34, 95% CI; 1.04-1.71, p=0.02), such that a 1-point increase in erHbO2 is associated with approximately 35% increase in the odds for good neurological outcome.

Conclusion:
Our results demonstrate that rSO2 and erHbO2 can predict good neurological outcome. erHbO2 may be a useful index for neuro-protection in patients with PCAS.
Abstract 9904: Trends in Enrollment, Patient Characteristics, Treatments and Outcomes of Older Adults With Non-ST-segment Elevation Acute Coronary Syndromes (ACS) in Clinical Trials
Authors: Bernacki Gwen M , Alexander Karen P , Newby L. Kristin , Yang Qinghong , Schulte Phillip , White Harvey D , Ohman E. Magnus , Mahaffey Kenneth W , Shah Bimal R , Giugliano Robert P , Armstrong Paul W , Harrington Robert A , Tricoci Pierluigi , Van de Werf Frans , Alexander John , Califf Robert M , Lopes Renato D
Published: April 2024

Introduction:
Whereas individuals aged ≥75 years account for >1/3 of non-ST-segment elevation (NSTE) ACS episodes and the majority of deaths due to NSTE ACS in current practice, little is known about their participation in NSTE ACS clinical trials.

Methods:
We studied 79,133 NSTE ACS patients enrolled in 11 phase III clinical trials (GUSTO IIb, PURSUIT, PARAGON-A, PARAGON-B, PRISM, PRISM-PLUS, GUSTO IV-ACS, SYNERGY, EARLY ACS, TRACER, APPRAISE-2) during 5 time periods (1994-97, 1998-01, 2002-05, 2006-10) over 17 years. We characterized the population according to age, patient characteristics, medical therapy, and outcomes (severe bleeding, 30-day mortality, 6-month mortality, 30-day composite of death or MI) and examined changes in these parameters over time.

Results:
Overall, 19.7% of patients enrolled in the selected trials were aged ≥75 years; while this proportion increased during the 1998-01 and 2002-05 periods, it declined in 2006-10 (Table). The prevalence of comorbidities varied (Table). Use of evidence-based medications at discharge among patients aged ≥75 years increased overall (aspirin 66.6 to 93.5%; beta-blockers 40.9 to 78.2%; thienopyridines 5.8 to 76.9%, lipid-lowering drugs 8.0 to 83.4%, ACE inhibitors 24.6 to 62.6% in 1994-97 to 2006-10). 30-day and 6-month mortality consistently declined. During the interval between 1994-97 and 2006-10, severe bleeding and the 30-day composite of death or MI for patients aged ≥75 years declined overall (2.0% to 1.6% for severe bleeding, and 17.6% to 9.3% for composite of 30-day death or MI).

Conclusions:
Despite significant improvements in clinical care and outcomes among patients aged ≥75 years, their enrollment in NSTE ACS clinical trials is not representative of the NSTE ACS population. Representative enrollment of elderly patients in clinical trials constitutes a critical unmet need to advance their evidence-based care and apply more novel approaches to lower morbidity and mortality.
Abstract 9933: Impact of Antiplatelet Therapy in Patients With Impaired Glucose Tolerance
Authors: Ueno Masafumi , Fujita Kosuke , Yamamoto Hiroyuki , Ikeda Tomoyuki , Suga Tatsuya , Yamaji Kenji , Ikuta Shinichiro , Kobuke Kazuhiro , Iwanaga Yoshitaka , Miyazaki Shunichi
Published: April 2024

Background:
Patients with diabetes mellitus (DM) have reduced clopidogrel-induced antiplatelet effects and increased rates of high platelet reactivity (HPR) compared with non-DM patients. Although approximately 40% of patients with coronary artery disease (CAD) have a pre-diabetic status characterized by impaired glucose tolerance (IGT). However, the impact of IGT on pharmacodynamic (PD) response to antiplatelet therapy is unknown.

Objectives:
To investigate the impact of IGT on PD response to antiplatelet therapy in patients with IGT.

Methods:
A 75g oral glucose tolerance test was performed in 52 stable CAD patients treated with maintenance aspirin and clopidogrel therapy. Blood samples were collected at 3 time-points (baseline, 1 and 2 hours after glucose load). IGT was defined as fasting plasma glucose of 110-126 mg/dl and 2 hour plasma glucose of 140-200 mg/dl. Platelet aggregation was assessed by light transmittance aggregometry using 5 and 20 μmol/L ADP stimuli. HPR rates was defined when both maximal aggregation was ≥ 59% with 20 μmol/L ADP and ≥ 46% with 5 μmol/L ADP.

Results:
There were 22 subjects (42%) who had IGT. At baseline, patients with IGT showed increased platelet reactivity at 5 μmol/L ADP (45.3±13.7 vs 38.6±13.4; p=0.09) and 20 μmol/L ADP stimuli (57.6±12.6 vs 47.5±14.3; p=0.01), and higher HPR rates (54.5% vs 16.0%; p=0.01) compared with non-IGT patients. Similar results were obtained at 1 hour [5 μmol/L ADP (43.1±13.7 vs 36.4±13.9; p=0.1), 20 μmol/L ADP (55.2±12.2 vs 45.4±14.3: p=0.01), HPR rates (36.4% vs 12.5%; p=0.08)], and 2 hours [5 μmol/L ADP (40.7±14.9 vs 35.8±13.9; p=0.2), 20 μmol/L ADP (52.5±12.4 vs 44.4±13.8: p=0.04), HPR rates (40.9% vs 8.3%; p=0.01)].

Conclusions:
Patients with IGT on dual antiplatelet therapy with aspirin and clopidogrel have enhanced platelet reactivity and increased rates of high platelet reactivity compared with non-IGT patients, suggesting platelet dysfunction which is independent of hyperglycemia may exist in pre-diabetic patients.
Abstract 9959: Chronic Administration of Pioglitazone and Pro-Oxidant Effects Within Chronic Hibernating Pig Hearts
Authors: Butterick Tammy A , Long Eric K , Duffy Cayla , Cabrera Jesús A , Holley Christopher T , Ward Herbert B , Kelly Rosemary F , McFalls Edward O
Published: April 2024

Background:
Glitazones have pleomorphic effects on myocardial metabolism. We hypothesized that the PPAR-gamma agent pioglitazone (PIO) would alter mitochondrial function and induce a pro-oxidant effect on chronically ischemic heart tissue.

Methods:
Eighteen pigs underwent a thoracotomy with placement of a fixed constrictor around the LAD artery. At 8-weeks post-instrumentation, they were given daily PIO (3 mg/kg) or placebo (P) in the chow for 4 weeks. Regional function by ECHO was measured at baseline and regional blood flows by μspheres were determined at baseline and during high-dose dobutamine (40 μg/kg/min). Using a high-speed drill, tissue was harvested and frozen for enzymatic analysis of high-energy nucleotides. Post-sacrifice, state 3 respiration was measured from isolated mitochondria and tissue levels of glutathionyl 4-oxo-2-nonenal (GS-ONE) were determined by liquid chromatography-tendem mass spectrometry measurement.

Results:
In all pigs, baseline regional wall thickening (%) was lower in the LAD versus Remote region (42±5% vs 58±5%; P<0.05). LAD blood flow when normalized to the remote region was 83±5% at baseline and 64±7% during dobutamine, demonstrating the presence of chronic ischemic myocardium. The energetic state in the PIO group was more unfavorable than the placebo group, as manifested by lower transmural ATP levels (1.61±0.22 vs 2.35±0.25 μmol/g; P<0.05) and depressed Phosphocreatine to ATP ratios (1.59±0.11 vs 2.11±0.16; P<0.05). As shown by the figure, animals that received chronic PIO had higher levels of oxidant stress, as measured by GS-ONE levels and depressed rates of mitochondrial state 3 respiration. In summary, chronic administration of pioglitazone has a pro-oxidant effect on chronically ischemic hearts and an unfavorable effect on myocardial energetics, potentially by altering activity within the mitochondrial electron transport chain.
Abstract 10007: Revascularization in Multivessel Coronary Artery Disease_Lower Early MACCE Rate With Multiple Arterial Bypass Grafting Than Percutaneous Coronary Intervention
Authors: Locker Chaim , Schaff Hartzell V , Daly Richard C , Malcolm Bell R , Frye Robert L , Stulak John M , Greason Kevin L , Dearani Joseph A , Joyce Lyle D , Pochettino Alberto , Li Zhuo , Lennon Ryan J , Lerman Amir
Published: April 2024

Objectives:
CABG and PCI are used for revascularization of multivessel coronary artery disease (MVCAD). However, limited information is available comparing the rates of in-hospital and 30-day major adverse cardiac and cerebrovascular event (early MACCE), including early death, stroke, myocardial infarction (MI), and repeat revascularization, among patients with multiple arterial CABG (MultArt) vs PCI.

Methods:
We reviewed 12,615 MVCAD patients with isolated primary CABG or PCI from 1993 through 2009. CABG patients (n=6,667) were grouped by number of arterial grafts into left internal mammary artery/saphenous vein (LIMA/SV) (n=5,712) or MultArt (n=955); PCI patients (n=5,948) into balloon angioplasty (BA) (n=1,020), bare metal stent (BMS) (n=3,242), and drug-eluting stent (DES) (n=1,686).

Results:
Early MACCE rate was significantly greater for PCI than CABG (8.5% vs 4.1% [P<.001]) and lower for MultArt than LIMA/SV or PCI (1.5% vs 4.5% and 8.5%, respectively [P<.001]). Stroke and early death rates were higher in CABG vs PCI (2.2% vs 0.4% [P<.001], and 1.5% vs 1.0% [P=0.01], respectively), whereas MI and repeat revascularization were lower (0.5% vs 6.0% and 0.3% vs 2.2%, respectively [P<.001]). Stroke and early death were similar in MultArt and PCI and lower vs LIMA/SV (0.6% and 0.4% vs 2.6%, and 0.5% and 1.0% vs 1.7%, respectively [P<.001]); MI and repeat revascularization rates were similar in MultArt and LIMA/SV and lower vs PCI (0.4% and 0.6% vs 6.0%, and 0.3% and 0.3% vs 2.3%, respectively [P<.001]). In propensity score-matched analysis, CABG had significantly improved early MACCE rate compared with BA (4.7% vs 13.2% [P<.001]), BMS (4.3% vs 8.3% [P<.001]), and DES (2.9% vs 5.5% [P=.008]), and MultArt compared with PCI (1.8% vs 7.8% [P<.001]) fig.

Conclusions:
In MVCAD patients undergoing isolated primary revascularization, CABG conferred lower early MACCE rate vs PCI. Early MACCE rate was markedly decreased after MultArt compared with LIMA/SV, BA, BMS, and DES.
Abstract 10111: Transcatheter Aortic Valve Implantation Without Intensive Care Unit Admission is Possible in Selected "Low Risk" Patients
Authors: Leclercq Florence , Iemmi Anais , Macia Jean Christophe , Lattuca Benoit , Agullo Audrey , Gervasoni Richard , Schmutz Laurent , Gandet Thomas , Nogues Erika , Nagot Nicolas , Albat Bernard , Cayla Guillaume
Published: April 2024

Introduction:
Admission to the intensive care unit (ICU) after transcatheter aortic valve implantation (TAVI) is a standard of care.

Hypothesis:
We assessed the hypothesis that TAVI can be performed safely without ICU admission in patients considered at low risk using simple clinical, ECG and echographic criteria.

Methods:
In this prospective monocentric cohort study we included all consecutive patients who underwent a TAVI procedure between December 2014 and May 2015. Low risk group included patients with LVEF > 40 %, transfemoral (TF) access, absence of severe pulmonary disease, stable hemodynamic state and absence of complications occurring until 2 hours after the procedure. High risk group included all other patients. Patients were admitted to the ICU or conventional cardiology unit depending on their risk evaluation. In-hospital major adverse events (VARC-2 criteria) were recorded in the two groups

Results:
On the 144 patients included, 67 were men (46.5 %), median age was 85 years (80-88) and median Euroscore II was 4.2 (3-6.9). The balloon expandable Edwards Sapien 3 valve was mainly used (n=118; 82%), with TF approach (n=136; 94.4% ) and general anesthesia (n=138; 95.8%). Of the 46 low risk patients (31.9%), only 1 was secondarily transferred to ICU due to non compressive pericardial effusion (minor complication) giving a negative predictive value of our triage strategy of 97.8% (CI:88.5-99.9). Conversely, of the 98 high risk patients, 40 developed major complications, mainly conductive disturbances. Positive predictive value was 40.8% (CI: 31.0-51.2). (Table 1)

By univariate analysis, the main pre procedural predictive factors of complications were use of self expandable prosthesis (p<0.00005) and right bundle branch block (p<0.004).

In conclusion, our results suggested that TAVI can be performed safely without ICU admission in selected patients. This new “minimalist” strategy may optimize efficiency and cost effectiveness of the procedure.
Abstract 10116: Polyunsaturated Fatty Acid Treatment and Post-discharge Outcomes Following Acute Myocardial Infarction
Authors: Greene Stephen J , Temporelli Pier Luigi , Campia Umberto , Vaduganathan Muthiah , Degli Esposti Luca , Buda Stefano , Veronesi Chiara , Butler Javed , Nodari Savina
Published: April 2024

Introduction:
Clinical trial data regarding efficacy of n-3 polyunsaturated fatty acids (PUFA) in improving outcomes following acute myocardial infarction (AMI) are mixed and large observational studies of non-trial populations are lacking.

Methods:
We collected data from 5 Italian Local Health Units for patients discharged with the primary diagnosis of AMI between January 1, 2010 and December 31, 2011. Using unique patient identifiers, patients were linked across government hospital discharge, medication prescription, and mortality databases and followed for 12 months post-discharge.

Results:
Overall, 2,425 (21.5%) of 11,269 patients received n-3 PUFA during follow-up at 1 g/day. Patients treated with n-3 PUFA tended to be younger, male, diabetic, and more likely to receive guideline medical therapy, including beta-blockers, ACE inhibitors/ARB, statins, and antiplatelet therapy (P<0.001; Table). After adjustment for patient characteristics and concurrent therapies, n-3 PUFA treatment was associated with reduction in death (HR 0.76, 95% CI 0.59-0.97) and recurrent AMI (HR 0.65, 95% CI 0.49-0.87) through 12 months.

Conclusions:
In this large, contemporary, observational study of patients hospitalized for AMI, n-3 PUFA treatment was independently associated with robust reduction in post-discharge clinical events.
Abstract 10274: It’s Complicated: Comorbidity, Self-efficacy, Self-care When Hospitalization and Quality of Life are Outcomes in Heart Failure
Authors: Buck Harleah G , Dickson Victoria V , Fida Roberta , Riegel Barbara , D’Agostino Fabio , Alvaro Rosaria , Vellone Ercole
Published: April 2024

Introduction:
Essential elements of heart failure (HF) self-care include engagement in daily behaviors that maintain physical stability (self-care maintenance) and recognition of symptoms with a timely response (self-care management). Comorbidity decreases self-efficacy or confidence in the ability to perform self-care which, in turn, impairs self-care behaviors. Comorbidity is also associated with increased hospitalization and poorer quality of life (QOL). Yet the manner in which comorbidity and self-efficacy interact to influence self-care, hospitalization, and QOL remains unclear.

Hypotheses:
1) Comorbidity and self-efficacy are determinants of self-care maintenance and management which in turn are determinants of hospitalization and QOL; 2) Comorbidity moderates the relationship between self-efficacy and self-care maintenance and management.

Methods:
An existing dataset of 628 symptomatic, older (mean age = 73, SD = 11) male (58%) Italian HF patients was analyzed using structural equation modeling and simple slope analysis. Measures used were the Charlson Comorbidity Index; Self-Care of Heart Failure Index (V6.2) for self-efficacy, self-care maintenance and self-care management; medical record review for hospitalization; and Minnesota Living with Heart Failure Questionnaire for QOL.

Results:
In the model higher comorbidity was associated with lower self-care management but not maintenance. Higher self-efficacy was associated with both higher self-care maintenance and management. Higher self-care maintenance was associated with fewer hospitalizations and better overall QOL. In the moderation analysis comorbidity moderated the relationship between self-efficacy and self-care maintenance. Higher comorbidity weakened the strength of the relationship between self-efficacy and self-care maintenance in post-hoc simple slopes analysis.

Conclusions:
The strength of the relationship between self-efficacy and self-care maintenance was a function of comorbidity. Self-care maintenance was associated with hospitalization and QOL. Therefore, tailoring interventions to improve self-efficacy at different levels of comorbidity may be key to impacting hospitalization and QOL in HF.
Abstract 10324: Balancing Work, Life and Health: A Mixed Methods Study Describing the Self-care Practices of an Older Working Population With Coronary Heart Disease (CHD)
Authors: Dickson Victoria , Jun Jin , Warren Nicholas , D'Eramo Melkus Gail
Published: April 2024

For the 3.5 million workers with CHD, daily self-care (i.e., treatment adherence, symptom monitoring and symptom management) must take place within the context of work.

Objective:
To describe the self-care practices of aging workers (>age 50 years) with CHD and examine the relationship of work organization (work processes and organizational practices), job-level factors and self-care.

Methods:
In this mixed methods study, 125 working adults with CHD completed valid and reliable instruments about organizational and job-related factors (job stress, job control, and work-life balance (WLB)), individual-level factors (mood, physical functioning) and self-care. A purposively selected subsample (n=40) participated in interviews about self-care within the context of work. Multiple regression examined the determinants of self-care. Then, qualitative data were analyzed using thematic content analysis, followed by data integration.

Results:
In this sample (69% Male, 85% White; mean age 59±5 years), 49% reported a recent myocardial infarction, 67% were overweight/obese and 60% had depressive symptoms. Overall, 68% reported adequate self-care (Self-Care Heart Disease Index mean 76±14) with significant differences in self-care by age, ethnicity and job type. There were significant interaction effects of job control and job type on self-care (
F
2.097,
p
=.038); and WLB and job type on self-care (
F
2.53,
p
=.024). Narrative accounts of self-care revealed that most struggled with diet and exercise due to job demands. These older workers with CHD reported competing WLB issues (e.g., as caregivers to adults vs. own health) for which they felt ill-equipped to manage. Those with poor self-care measured quantitatively reported feeling stressed and fatigued which they attributed to their job. Few interpreted the symptoms as related to CHD. Workers were selective in whom they discussed their CHD, self-care needs and daily symptoms, articulated as fear of discrimination and quantified as workplace injustice (mean 23±6).

Conclusions:
Self-care is challenging for many older workers with CHD and influenced by multi-dimensional factors. In this population with CHD, WLB encompasses balancing self-care with job and daily life responsibilities.
Abstract 10327: Automated Quantitative Modeling of the Aortic Root by Real-Time 3D TEE Predicts Optimal Valve Size for TAVR Planning When Contrast CT is Contraindicated
Authors: Liu Shizhen , Meduri Christopher , Rajagopal Vivek , Kauten James R , Rinehart Sarah J , Polsani Venkateshwar , Zhou Xiao , Qian Zhen , Martin Randolph , Mansi Tommaso , Houle Helene , Vannan Mani A
Published: April 2024

Background:
While CT is the modality of choice for TAVR planning, contrast CT may be not be possible in those with renal dysfunction. We tested whether automated quantitative modeling of the aortic root by real-time 3D TEE (RT3D-TEE) was a useful alternative in these patients.

Methods:
44 patients (76 ± 10 years old) with severe AS who could not have contrast CT for TAVR planning had RT3D TEE during TAVR procedure. The aortic root was modeled automatically using the previously validated eSie valves (Siemens, CA). From the dynamic model maximum, minimum and mean aortic annulus diameters, aortic annulus perimeter, and aortic annulus area were measured in mid/peak systole, whichever was larger. The predicted valve size based on these parameters was compared to the actual valve size used during TAVR (balloon and self-expanding valves).

Results:
The valve size predicted by automated quantitative RT3D-TEE had excellent correlation with the actual valve size (indexed by body surface area, r=0.96 for mean diameter, 0.94 for perimeter and area derived diameters, p < 0.0001, Figure-upper panel graph). The agreement (Kappa statistic) between actual valve size used and that predicted by RT3D-TEE was 0.82, 0.64 and 0.58, p < 0.0001 for mean diameter, and perimeter and area derived diameters (lower left table). The red dots in the graph in the upper panel show cases where there was discrepancy between 3-D TEE predicted and actual valve size used. Mean diameter had the fewest "underestimation" of the valve size vs. perimeter and area derived prediction. An example of quantitative aortic root modeling in a patient who had TAVR with a 31 mm self-expanding valve, with no PVL (lower right panel).

Conclusion:
Automated quantitative modeling of the aortic root by real-time 3-D TEE in severe AS is feasible, rapid and an excellent alternative to contrast CT when the latter is contraindicated, for TAVR planning. Mean annulus diameter measured by 3D-TEE seems to be the best predictor of the optimal valve size.
Abstract 10341: Prevalence and Factors Associated With Statin Use Among a Nationally Representative Sample of US Adults - National Health and Nutrition Examination Survey, 2011-2012
Authors: Adedinsewo Demilade , Onwuanyi Anekwe
Published: April 2024

Background:
The 2013 AHA/ACC guidelines recommend the use of statins for adults ≤75 years who have clinical ASCVD (IA) and for primary prevention among persons aged 40 – 75 with diabetes mellitus and LDL btw 70 - 189mg/dl (IA). The aim of this study was to estimate the prevalence and likelihood of statin use among selected statin benefit groups.

Methods:
Using data from the National Health and Nutrition Examination Survey (NHANES) for the 2011 - 2012 cycle, we examined 5,319 adults aged 20 years and older. We estimated weighted frequencies and proportions with confidence intervals for the entire sample and for persons with diabetes and LDL ≥70 or a diagnosis of dyslipidemia, denoted statin benefit group 1 (SBG1) and for persons with history of ASCVD, statin benefit group 2 (SBG2). We constructed a multivariable logistic regression model to estimate the odds of statin use among persons in SBG1. All analyses were conducted using SAS survey procedures for complex sample data and evaluated at α=0.05.

Results:
Among persons in SBG1 (mean age: 61yrs), 59.5% (95% CI: 53.0 – 66.1), an estimated 10.6 million persons and 63.5% (95% CI: 55.6 – 71.4) of persons in SBG2 (mean age: 65yrs), an estimated 10.8 million persons were on a statin. A sub-population analysis among persons aged 40 – 75 showed statin use to be 58.8% (95% CI: 51.5 – 66.1) for persons in SBG1. Overall, an estimated 38.6 million Americans are on a statin, an increase from 24 million in 2003-2004. In adjusted models, uninsured persons and Hispanics compared to Whites were less likely to be on a statin.

Conclusion:
The prevalence of statin use among US adults has tripled since 1999-2000. However racial disparities and lack of insurance remain a barrier to statin use. Our study provides a baseline estimate of statin use in the noninstitutionalized civilian adult population just prior to the introduction of the new guidelines and provides a reference for evaluating the impact of the 2013 guidelines on statin utilization.