bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15649: Open-Chest Intramyocardial Delivery of Exosomes From Cardiosphere-Derived Cells (CDCs) Mimics Cellular Postconditioning: Decreased Infarct Size and Improved Perfusion in a Pig Model of Acute Myocardial Infarction
Authors: Gallet Romain , Dawkins James , Simsolo Eli , Tseliou Eleni , Middleton Ryan , Valle Jackelyn , Kreke Michelle , Smith Rachel , Marbán Linda , Marbán Eduardo
Published: April 2024

Background:
Various lines of evidence indicate that exosomes mediate the therapeutic effects of cardiosphere-derived cells (CDCs). However, retention and efficacy of exosomes may be limited after intracoronary (IC) delivery due to their very small size (30-150 nm diameter).

Objectives:
We sought to assess the optimal dosing and delivery techniques for exosomes, and their ability to reduce microvascular obstruction (MVO) and infarct size (IS) in a pig model of ischemia/reperfusion.

Methods:
Acute myocardial infarction (AMI) was induced in 23 mini-pigs by balloon occlusion of the mid-LAD for 1.5h. Thirty minutes after reperfusion, pigs received, by prior random assignment, IC injection of CDC-derived exosomes (1.5mg [n=3] or 15mg [n=5] of exosome protein), vehicle [n=6], or transepicardial intramyocardial injection (IM) of exosomes (15mg [n=4] or 7.5mg [n=5]) via median sternotomy. Pigs were sacrificed 48 hr post-MI to measure area at risk (AAR), IS and MVO utilizing gentian violet, TTC (2,3,5-triphenyl tetrazolium chloride) and thioflavin staining respectively. Left ventricular ejection fraction (LVEF) was measured by contrast ventriculography before injection and at endpoint.

Results:
AAR was identical in all groups (averaging 22±4% of LV, P=0.65 among groups). Consistently, LVEF was similar in all groups before treatment. IC delivery of high-dose exosomes (15mg) decreased MVO (43±6% vs. 56±7%, P=0.02) whereas IC low-dose (1.5mg) did not (54±6%, P=0.66). However, IC exosomes failed to decrease IS regardless of dose. In contrast, both IM doses decreased MVO (43±6% for 15mg and 25±14% for 7.5mg, P=0.04 and P<0.0001 respectively) and IS (67±6% for 15mg, 57±15% for 7.5mg vs. 80±6 for placebo, P=0.04 and P=0.003 respectively). At both IM doses, LVEF at endpoint was higher in exosome-injected pigs compared to vehicle (P=0.03).

Conclusion:
Intracoronary injection of CDC-secreted exosomes decreases MVO at high doses, but fails to reduce IS. In contrast, both low- and high-dose exosomes reduce IS and MVO after intramyocardial delivery, mimicking the cardioprotection seen with CDCs themselves (cellular postconditioning). These results indicate that IM delivery may be more suitable for exosome therapy of myocardial disease.
Abstract 15668: Mechanical Circulatory Support With Veno-Arterial Extracorporeal Membrane Oxygenation for Refractory Cardiogenic Shock in Elderly Patients: Results From the Extracorporeal Life Support Organization (ELSO) Registry
Authors: Lorusso Roberto , Gelsomino Sandro , Mendiratta Priya , Prodhan Parthak , Rycus Peter , MacLaren Graeme , Brogan Thomas , Chen Yih-Sharng , Maessen Jos , Hou Xiaotong , Parise Orlando , Thiagarajan Ravi
Published: April 2024

Introduction:
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory acute cardiogenic shock is increasingly applied in adult patients. Patient age, however, represents still a controversial issue and data about VA-ECMO in elderly patients have been poorly reported in this setting.

Hypothesis:
The Extracorporeal Life Support Organization (ELSO) Registry was analysed to assess the in-hospital outcome of elderly patients (≥ 70 years) undergoing VA-ECMO because of acute refractory cardiogenic shock.

Methods:
Mean age of the total adult patient cohort (n=5,408) was 53.0±15.7 years (range 18-91 years). The elderly group included 735 patients (13.6%), with a mean age of 75.2±4.4 years, with pre-ECMO cardiac-related surgical or interventional procedures performed in 134 cases (18.9%). The mean duration of VA-ECMO in this group was 100.7± 90.9 hours (as compared to 137.7±146.1 hours, in younger group)(p<0.001).

Results:
Overall survival to hospital discharge was 41.4% (2,657/5,408), with 30.5% (224/735) in the elderly, and 43.1% (2,016/4,673) in younger patients (p<0.05), respectively. In terms of complications, older patients showed higher rates (p<0.001) of bleeding, of infection, acute renal failure, renal replacement therapy, and need of inotropic drugs.

Conclusions:
Despite higher mortality and morbidity rates as compared to younger subjects, elderly patients undergoing VA-ECMO for refractory cardiogenic shock have still an acceptable outcome in such a challenging clinical scenario, indicating that patient age should not represent an absolute contraindication in the therapeutic decision-making.
Abstract 15687: Early Repolarization and Implantable Cardioverter Defibrillator Events in Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER)
Authors: So Petsy P , Gerull Brenda , Angaran Paul , Steinberg Christian , Herman Adam , Champagne Jean , Sanatani Shubhayan , Chakrabarti Santabhanu , Healey Jeffrey S , Chauhan Vijay S , Birnie David H , Yee Raymond , Klein George J , Bennett Matthew T , Leather Richard , Gollob Michael H , Simpson Christopher S , Talajic Mario , Gardner Martin , Krahn Andrew D
Published: April 2024

Introduction:
Early repolarization (ER) has been implicated as a rare primary arrhythmic disorder, and a more common cofactor is arrhythmia risk. Our objective was to determine if ER is associated with increased implantable cardioverter defibrillator (ICD) events in patients with unexplained cardiac arrest and their first degree relatives (FDR).

Methods:
The cardiac arrest survivors with preserved ejection fraction registry (CASPER) is a national registry that systematically examines unexplained cardiac arrest probands and their FDR. The presence of ER was identified in serial ECGs. ER was defined as J-point elevation ≥ 0.1 mV above the isoelectric line in ≥ 2 contiguous inferior (II, III, avF) or lateral leads (I, avL, V4-V6), excluding V1-V3. ICD event rates, including appropriate ICD shocks and anti-tachycardia pacing (ATP) and mortality were assessed.

Results:
One hundred and seventy-nine subjects from 13 Canadian sites were studied (age 46±17 years, 89 males). Overall, 99/104 (95%) probands and 6/75 (8%) FDR received an ICD. Eighty-eight probands and 3 FDR had at least one follow-up visit. After 4 ± 2 years of follow-up, 15 probands had appropriate ICD shock (17%), 13 had ATP (15%) and 22 had either (25%). A total of 566 ECGs were analyzed for ER (3 ± 2 ECGs/subject). Twenty-nine of the 88 probands had ER (33%), and 6 had appropriate ICD shock (21%), 5 had ATP (17%) and 9 had either (31%). For those who had ER, Cox regression demonstrated trends towards a higher risk of first ICD shock or ATP (HR=1.9, 95% CI 0.76-4.73, p=0.17), first ICD shock (HR =2.1, 95% CI 0.81-5.17, p=0.13) and first ATP (HR=1.6, 95% CI 0.49-5.32, p=0.42). ATP was seen in 1 FDR and none had ICD shock. For those who had an ICD event and ER, a diagnosis was obtained in 5/9 patients: ER syndrome in 1, long QT syndrome in 3 and mitral annular ventricular tachycardia in 1. The remaining 4 had idiopathic ventricular fibrillation. One proband died after 3.2 years of follow-up with a confirmed diagnosis of sarcoidosis without ER.

Conclusion:
ER may be associated with a higher risk of recurrent ICD events in apparently unexplained cardiac arrest patients, especially if the underlying etiology is presumed electrical rather than structural.
Abstract 15790: Neurologic Impact of Left Atrial Appendage Exclusion in Mitral Valve Surgery, a Retrospective Study
Authors: Ruka Emmeline , Voisine Émile , Dagenais François , Chauvette Vincent , Voisine Pierre
Published: April 2024

Context:
Up to 40% of patients undergoing isolated mitral valve surgery develop atrial fibrillation (AF). AF is a significant risk factor for stroke and 90% of clots responsible for AF-related neurological events form in the left atrial appendage (LAA). LAA exclusion (LAAe) could potentially reduce post-operative neurological complications in patients undergoing mitral valve surgery.

Methodology:
Single center retrospective cohort study with prospectively collected data including all patients undergoing mitral valve surgery between January 2003 and April 2014. Univariate analysis and multivariate analysis with stepwise approach were performed.

Results:
Results were obtained for 2728 patients who met the inclusion criteria. Of these, 406 (14.9%) had a LAAe. This group of patients suffered more frequently from pre-operative AF (86.7% vs 35.1%, p<0.0001) and had more concomitant Maze procedures (78.3% vs 12.3%, p<0.0001) than the group of patients who did not have LAAe (n-LAAe). By univariate analysis, in-hospital mortality was comparable in the LAAe vs n-LAAe groups (4.7% vs 6.5%, p=0.18). The risks of post-operative stroke (3.0% vs 3.5%, p=0.77) and transient ischemic attack (0.5% vs 0.4%, p=0.70) were also comparable. No difference in reoperation for bleeding between the two groups was observed (5.9% vs 6.8%, p=0.59). By univariate analysis, the presence of AF (pre- or post-operative) did not have a significant impact on mortality (p=0.48 and p=0.89, respectively). There was a significant difference in long-term survival between the LAAe group and the n-LAAe group (p=0.0007, median follow-up 2.4 years). By multivariate analysis, LAAe was identified as an independent protective factor from long-term mortality [OR 0.47; CI95% (0.25-0.89)]. The performance of an isolated Maze procedure [OR 0.66; CI95% (0.36-1.21)] did not have a significant impact on mortality.

Conclusion:
LAAe during mitral valve surgery is an independent protective factor from long-term mortality, without increasing peri-operative risks of bleeding or new onset AF. However, LAAe does not protect from neurologic events in the peri-operative period. Unlike LAAe, an isolated Maze procedure did not have an impact on long-term survival.
Abstract 15859: Interrupting Prolonged Sitting Reduces Resting Blood Pressure and Plasma Norepinephrine in Adults With Type 2 Diabetes
Authors: Dempsey Paddy C , Sacre Julian W , Straznicky Nora E , Lambert Gavin W , Cohen Neale , Owen Neville , Kingwell Bronwyn A , Dunstan David W
Published: April 2024

Interrupting prolonged sitting with frequent short bouts of light-intensity physical activity reduces blood pressure (BP) in overweight, non-diabetic adults, however, the effects in adults with type 2 diabetes (T2D) have not been investigated. This study examined the effects of two types of activity breaks (light-intensity walking or simple resistance activities) compared to continuous, uninterrupted sitting on resting BP and plasma norepinephrine (NE) in adults with T2D. In a randomized crossover trial, 24 inactive adults with T2D (14 male; 62 ± 6 y; BMI 33.0 ± 3.4 kg/m
2
) consumed standardized breakfast and lunch meals during 3 x 8 h conditions (6-day washout): i) SIT: uninterrupted sitting (control); ii) LW: sitting + 3 min bouts of Light-intensity Walking (3.2 km/h every 30 min); and iii) SRA: sitting + 3 min bouts of Simple Resistance Activities (half-squats, calf raises, gluteal contractions and knee raises) every 30 min. Resting seated BP was measured hourly (mean of 3 recordings, performed ≥ 25 min after activity). Venous blood was drawn every 30 min for the plasma NE assay, ≥ 25 min after activity. As illustrated in figures 1A and 1B, compared to SIT, both LW and SRA reduced BP (
P
< 0.001); with the effect being more pronounced with SRA (
P
< 0.01 vs. LW). Similarly, compared to SIT, both LW and SRA reduced plasma NE concentrations, with SRA significantly lower than LW (
P
< 0.01). In conclusion, simple interruptions to sitting lowered resting BP and plasma NE concentration in adults with T2D. Reduced sympathetic vasoconstrictor tone may contribute to the observed hypotensive effect. With the ubiquity of sedentary behaviours and the low adherence to structured exercise, this approach is a practical strategy which may contribute to BP control.
Abstract 11275: ST-Segment Elevation in Lead aVR Strongly Predicts In-hospital Mortality in Patients With Type A Acute Aortic Dissection
Authors: Kosuge Masami , Uchida Keiji , Karube Norihisa , Ebina Toshiaki , Hibi Kiyoshi , Iwahashi Noriaki , Maejima Nobuhiko , Matsuzawa Yasushi , Masuda Munetaka , Kimura Kazuo
Published: April 2024

Introduction:
Early identification of high-risk patients is crucial for appropriate management in type A acute aortic dissection (AAD). ECG is useful for this purpose because it is readily available and rapidly interpretable at presentation.

Hypothesis:
In type A AAD, ischemic ST-T change at presentation is associated with poor outcomes. ST-segment elevation in lead aVR (ST↑aVR) is an ECG marker of severe acute myocardial ischemia, and therefore, may provide important prognostic information.

Methods:
We studied the relation of ECG findings to clinical features on admission and in-hospital death in 294 patients who were admitted within 12 h from symptom onset and underwent urgent surgery for type A AAD. Patients with bundle branch block or left ventricular hypertrophy were excluded. Patients were divided into the 3 groups according to admission ECG findings: no significant ST-T changes (n=99, G-A); the absence (n=151, G-B) or the presence (n=44, G-C) of ST↑aVR ≥0.5 mm with ST-T changes in other leads. Hemoglobin (Hb), creatinine (Cr), D-dimer, and cardiac-specific troponin were measured on admission.

Results:
There were no differences in age, sex, time to admission or Hb level in the 3 groups. In G-A, G-B, and G-C, systolic blood pressure was 130±23, 131±33, and 88±27 mmHg (p<0.01); heart rate was 70±14, 72±19, and 94±23 bpm (p<0.01); the levels of Cr were 0.9±0.6, 1.0±0.7, and 1.3±1.0 mg/dl (p=0.01); D-dimer was 26±43, 33±40, 62±50 μg/ml (p=0.02), the rates of positive-troponin were 3%, 14%, and 41% (p<0.01); shock were 2%, 21%, and 71% (p<0.01); cardiac tamponade was 3%, 19%, and 64% (p<0.01); moderate/severe aortic regurgitation was 4%, 28%, and 43% (p<0.01); coronary ostial involvement was 3%, 10%, and 32% (p<0.01); concomitant coronary artery bypass surgery was 2%, 7%, and 14% (p=0.03); in-hospital death was 1%, 6%, and 36% (p<0.01), respectively. Multivariate analysis showed that as compared with G-A, odds ratio (95%CI) for in-hospital death associated with G-B and G-C were 1.90 (0.68-4.08; p=0.19), and 34.4 (8.01-73.2; p<0.01), respectively.

Conclusions:
In patients with type A AAD, ST↑aVR on admission ECG strongly predicts in-hospital death. Our findings suggest that ST↑aVR is a simple but reliable tool for an early identification of high-risk patients.
Abstract 11359: Relationship of Incident Atrial Fibrillation to the Electrocardiographic Strain Pattern in Hypertensive Patients With Electrocardiographic Left Ventricular Hypertrophy
Authors: Okin Peter M , Wachtell Kristian , Kjeldsen Sverre E , Devereux Richard B
Published: April 2024

Background:
Atrial fibrillation (AF) is strongly related to hypertension and to left ventricular hypertrophy (LVH) and both regression of ECG LVH and achievement of lower systolic blood pressure (SBP) are associated with lower incidence of AF. The ECG strain pattern of lateral ST depression and T-wave inversion has been associated with more severe LVH, decreased LV systolic function and an increased risk of cardiovascular mortality and morbidity, including new heart failure (HF). However, whether ECG strain is associated with an increased risk of new AF is unclear.

Methods:
Risk of new-onset AF was examined in relation to the presence of the strain pattern on baseline ECG in 7921 hypertensive patients with ECG LVH with no history of AF, who were in sinus rhythm on their baseline ECG, had baseline strain determination and were randomized to losartan- vs atenolol-based treatment.

Results:
During 4.7±1.1 years follow-up, new-onset AF was diagnosed in 621 patients (7.8%). Baseline ECG strain was present in 882 patients (11.1%) and was associated with a significantly higher 5-year incidence of AF in Kaplan-Meier estimates (12.2 vs 7.4%, p<0.001) and with a 66% greater risk of new AF in a univariate Cox model (HR 1.66, 95% CI 1.34-2.06, p<0.001), compared with the absence of ECG strain. After adjusting for other univariate predictors of new AF in this population, including age, sex, race, prior anti-hypertensive treatment, randomized treatment allocation, prevalent diabetes, history of ischemic heart disease, prior myocardial infarction, stroke or HF, baseline serum cholesterol and urine albumin/creatinine ratio entered as standard covariates and incident HF and on-treatment diastolic BP, SBP, heart rate and Cornell product LVH entered as time-varying covariates, ECG strain remained associated with a 39% greater risk of new-onset AF (HR 1.39, 95% CI 1.09-1.76, p=0.008).

Conclusions:
The presence of strain on a baseline ECG is strongly associated with an increased risk of developing new-onset AF in hypertensive patients with ECG LVH, independent of other AF risk factors and the effects of incident HF, LVH regression and SBP reduction. These findings suggest that hypertensive patients with ECG strain should be followed closely for development of new AF.
Abstract 11394: Decrease of Senescence Marker Protein-30 in Aging Impairs Collateral Growth Under Ischemia
Authors: Saitoh Shu-Ichi , Yamauchi Hiroyuki , Owada Takashi , Miura Shunuke , Kokubun Tomoki , Takeishi Yasuchika
Published: April 2024

Aging decreases collateral-dependent flow recovery following ischemic arterial obstruction. However, the critical management has been lacked in clinical setting. Senescence marker protein-30 (SMP30) is a novel aging marker, which is assumed to act as an anti-aging factor in various organs. Therefore, we studied the effect of SMP30 on ischemia-induced collateral growth in C57BL/6 mice with young [8 weeks old (W)] and old (92 W), and SMP30 knockout (KO) mice (8 W). The SMP30 expression in gastrocnemius tissue was decreased in old mice compared to that of young mice. The recoveries of cutaneous blood flow in hindlimb after femoral artery ligation and tissue capillary density were suppressed in old and SMP30 KO mice compared to those in young mice. Nitric oxide generation induced by L-arginine was lower in old and SMP30 KO mice than that in young mice. The levels of NADPH oxidase activity and superoxide production in the ischemic tissue were higher in old and SMP30 KO mice than in young mice. The phosphorylated eNOS and Akt levels and VEGF levels in ischemic muscle were lower in old and SMP30 KO mice than in young mice (VEGF: Old mice 266±32, SMP30 KO 238±34, Young 414±48 pg/mg,
P<0.01
). Decrease of SMP30 exacerbates oxidative stress related to NADPH oxidase activity enhancement and impairs Akt-eNOS pathway, which leads to rarefaction of vasculogenesis induced by ischemia. These results suggest that SMP30 plays a key role in disrupting collateral growth under ischemia in aging.
Abstract 11425: Left Ventricular Function and Coronary Artery Disease in Patients With and Without Diabetes. Long-term Follow-up - Revision-dm2 Trial
Authors: Hueb Thiago O , Martinelli Filho Martino , Garcia Rosa M , Peixoto Gisele L , Siqueira Sergio , da Silva Rocha Mauricio , Cesar Luiz A , Hueb Whady , Ramires Jose A , Kalil Filho Roberto
Published: April 2024

Introduction:
It is assumed that the left ventricular dysfunction due to ischemic cardiomyopathy is a major determinant of poor prognosis of survival when compared to preserved ventricular function. However, it is unknown the role of diabetes in long-term prognosis in this patient group compared to patients without diabetes.

Hypothesis:
To investigate whether the presence of diabetes affects the prognosis in ventricular function in long-term follow-up.

Methods:
We prospectively analyzed in a database, outpatients, previously submitted to percutaneous, surgical or clinical treatment. All patients had multivessel disease and LVEF measures. The events considered were overall mortality, nonfatal myocardial infarction, stroke and additional interventions.

Results:
From January 2009 to January 2010 were selected 918 consecutive patients, followed until May 2015. They were grouped into: G1, 266 diabetic patients with ventricular dysfunction, G2, 213 diabetic without dysfunction, G3, 213 patients without diabetes and without dysfunction and G4, 226 patients without diabetes and with dysfunction. The mortality rate was 21.6%, 6.1%, 4.2% and 10.6% for Groups 1, 2, 3 and 4 respectively. (p <0.001). The incidence of nonfatal myocardial infarction was 5.3%, 0.5%, 7.0% and 2.6% for groups 1, 2, 3 and 4 respectively (p <0.001). Stroke occurred at 0.40% 0.45%, 0.90% and 0.90% in groups 1, 2, 3 and 4 respectively (p = NS). Further interventions occurred in 3.8%, 11.7%, 10.3% and 2.6% for groups 1, 2, 3 and 4 respectively (p <0.001).

Conclusion:
In this sample, regardless of the treatment received, diabetes mellitus added higher risk of cardiovascular events in patients with coronary artery disease and left ventricular dysfunction.
Abstract 11485: New Metrics of Postoperative Mechanical Ventilation Duration After Congenital Heart Surgery Reveal Variation Across Hospitals
Authors: Gaies Michael , Werho David , Ghanayem Nancy , Tabbutt Sarah , Costello John , Scheurer Mark , Pasquali Sara K , Donohue Janet , Zhang Wenying , Banerjee Mousumi , Schwartz Steven
Published: April 2024

Background:
Pediatric cardiac surgical programs aim to limit duration of postoperative mechanical ventilation (POMV) to reduce complications and hospital stay. Measuring casemix-adjusted duration of POMV across hospitals might elucidate differential performance and identify improvement opportunities.

Methods:
All surgical hospitalizations in the Pediatric Cardiac Critical Care Consortium (PC
4
) clinical registry from 10/2013-8/2015 were used to create a model predicting casemix-adjusted total duration of POMV using zero-inflated negative binomial regression and validated with 1000 bootstrap samples. From the model we developed metrics based on observed-to-expected POMV: early extubation success/failure, POMV reduction, and total hours of POMV saved/lost (
Table 1
). We ranked hospitals on each metric (1-15, 1=best) and calculated an average ranking across metrics to identify high and low performing hospitals.

Results:
The cohort included 4739 hospitalizations from 15 hospitals: 53% were infants and 22% had high complexity surgery. The final model included age, weight-for-age z-score, prematurity, pre-operative MV, extracardiac anomalies, procedure complexity, and bypass time. The model was well-calibrated to predict mean duration of POMV for groups of patients.
Table 1
displays the range and median of hospital rates on each of the four metrics, demonstrating variation across the group. The average ranks across these POMV duration metrics suggested two positive outlying hospitals (average rank across all 4 metrics = 1.75) and five hospitals with consistently lower performance (average 8.75-11.25).

Conclusions:
We developed novel casemix-adjusted metrics of hospital performance to limit duration of POMV following pediatric cardiac surgery, and identified wide variation in relative performance across centers. These metrics may suggest opportunities for improvement when evaluated in context with other perioperative quality measures.
Abstract 11639: Multivessel Versus Culprit-only Revascularization for Patients With St-segment Elevation Myocardial Infarction and Multivessel Disease Undergoing Primary Percutaneous Coronary Intervention
Authors: Zheng Wen , Zhao Xue-Dong , Zhang Yu-Jiao , Nie Shao-Ping
Published: April 2024

Introduction:
Primary percutaneous coronary intervention (PCI) to recanalize the infarct related artery (IRA) has become the first-choice therapy for ST-segment elevation myocardial infarction (STEMI) during past decades, while the value and optimal timing for PCI in non-IRA with stenosis is unknown.

Objective:
To examine the long-term outcomes and timing strategy for complete revascularization.

Methods:
1,039 STEMI patients with multivessel disease were divided into who received only-IRA PCI (555 patients) or complete revascularization including immediate PCI during the index-procedure (57 patients) or staged PCI within 90 days from the index-procedure (427 patients). The primary outcome was a composite of cardiac death, myocardial reinfarction, ischemic stroke or repeat revascularization.

Results:
During a mean follow-up of 47 months, the primary outcome occurred in 146 patients with only-IRA PCI and 102 patients with complete revascularization respectively (HR for complete revascularization,0.633;95%CI,0.445-0.900;
P
=0.011). This benefit mainly showed on the decreased risk for cardiac death, MI and repeat revascularization. The differences of the primary outcome between immediate PCI and staged PCI was non-significant (HR, 3.910;95%CI,0.852-17.949;
P
=0.079), but staged time interval was associated with risk-adjusted outcomes (HR 0.886;95%CI,0.797-0.984;
P
=0.024). A further analysis suggested 10 days or later could be a safe cutoff point for PCI in non-IRA (HR, 0.213;95%CI,0.063-0.717;
P
=0.013).

Conclusion:
In patients presenting for primary PCI with multivessel disease, complete revascularization significantly lowered the rate of the long-term endpoint compared with treating only the IRA. The optimal time for treating non-IRA assigned over 10 days after the index-procedure could improve survival.
Abstract 11766: Long Term Follow-up and Outcome of Atrial Fibrillation Patients With Left Atrial Appendage Obliteration Using Wireless Absorbable Occluders
Authors: Sideris Eleftherios , Toumanides Savvas , Agricola Tullio , Moulopoulos Spyridon
Published: April 2024

Introduction:
Metal occluders for the left atrial appendage (LAA) have been associated with morbidity that prevents their use as a primary approach for stroke prevention, in the majority of patients with atrial fibrillation(AF). Information on their long term outcome is limited. We hypothesize that a safe and effective occluder that reduces this morbidity with good long term outcome, could potentially replace anticoagulation in all patients with AF.

Methods:
The Transcatheter Patch (TP) is an absorbable wireless device made by inflatable polyurethane. It was successfully implanted in the LAA for stroke prevention in 27/30 high risk for stroke patients (CHADS2 score>3) from 2005-2012. The patient age varied from 28-89 years and the LAA mouth diameter from 12-24 mm. No patient received supplemental anticoagulation. The patients were followed by transesophageal echocardiography (TEE) at 1 month, 6 months and one year. They had yearly clinical follow-ups, thereafter. The results along with the clinical outcome were analyzed.

Results:
All 27 patients had uncomplicated implantation with full occlusion of the LAA. There was progressive decrease of the occluder size at 1 month (50% of the original), 6 months (20%) and one year (5%), maintaining the full occlusion. No new thromboembolic episodes, or other device related complications were noticed during the first year or in the subsequent clinical follow-up (max. 10, median 5 years). However, 4 deaths were noticed in this group for unrelated to AF causes (cancer, aortic aneurysm, renal failure etc).

Conclusion:
It appears that the wireless absorbable occluder used succeeded in preventing thromboembolic episodes with no morbidity both on early and on long term follow-up. The occurence of several unrelated to the procedure deaths in this high risk group necessitates the performance of long term trials in a lower risk group of AF patients. Providing that the favorable acute and long term results are maintained, use of the TP device for LAA closure could be preferable to anticoagulation for stroke prevention, in patients who are currently not indicated for LAA closure.
Abstract 11843: Comparison of Prognostic Value Between Carotid Plaque Score and Intima-Media Thickness in Patients With Acute Coronary Syndrome
Authors: Nakahashi Takuya , Tada Hayato , Sakata Kenji , Mori Mika , Hayashi Kenshi , Takamura Masayuki , Kawashiri Masa-aki , Yamagishi Maasakazu
Published: April 2024

Introduction:
Although both carotid plaque score (cPS) and intima-media thickness (cIMT) determined by carotid ultrasounds have been shown to reflect the severity of coronary atherosclerosis, few data exist regarding the direct comparison of their prognostic values in patients with established atherosclerotic vascular disease.

Hypothesis:
Calculation of cPS which is the reflection of the cumulative atherosclerotic burden of carotid artery is superior in predicting future cardiovascular events compared with only measurement cIMT in common carotid artery.

Methods:
We examined 263 patients (195 male; mean age, 68±11 years) with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention. The cPS was computed by summing the maximal thickness of plaques in each segment on both side (a + b + c + thickness of the contralateral plaques in each segment on both sides; Figure A). The primary endpoint of this study was major adverse cardiovascular and cerebrovascular events (MACCE) defined as all-cause death, myocardial infarction, stoke, target vessel revascularization, and coronary artery bypass grafting. Renal function was determined by estimated glomerular filtration rate (eGFR).

Results:
During follow-up duration (median 3.8 years, interquartile range: 1.2 to 6.1 years), 95 MACCE were occurred. Multivariate Cox proportional hazard regression analysis revealed that eGFR (hazard ratio [HR], 0.81; 95% confidence interval [CI], 0.66-0.99) and cPS (HR, 1.33; 95% CI, 1.05-1.69) with a 1-SD increase were significantly associated with MACCE, whereas, cIMT was not. Stratification of patients based on the tertiles of cPS was shown in Figure B. Addition of either cPS or cIMT over the eGFR changes C-statistic with nonsignificant. However, the addition of cPS to eGFR significantly improved net reclassification index (0.28, p <0.05), but not cIMT.

Conclusions:
The cPS provides superior risk stratification in patients with ACS compared with cIMT.
Abstract 11847: Remote Ischemic Conditioning by Single Cuff Inflation Improves Aortic Elastic Properties and Endothelial Glycocalyx Thickness in Acute Myocardial Infarction Patients
Authors: Ikonomidis Ignatios , Vlastos Dimitrios , Andreadou Ioanna , Efentakis Panagiotis , Varoudi Maria , Pavlidis George , Makavos George , Vlachos Stefanos , Mpenas Dimitrios , Triantafyllidi Helen , Seitanidi Eleni , Iliodromitis Efstathios K , Lekakis John
Published: April 2024

Background:
Remote ischemic conditioning attenuates ischemia-reperfusion injury in patients with STEMI. However, its effects on vascular function and biochemical mechanisms are not fully defined.

Methods:
We examined 110 patients with STEMI and 30 healthy controls. Patients were randomised in 2 remote ischemic conditioning protocols after a baseline assessment of vascular function (T0), a) one with two ischemic conditioning stimuli by brachial cuff inflation of both arms at 200mmHg for 5 min, separated by 15min, and each followed by vascular assessment (T1,T2), and a final vascular assessment (T3), 25 min after 2nd cuff deflation (double cuff inlation,n=60 ) or b) a second with omission of the second cuff inflation (single cuff inflation-n=50).In both protocols we measured a) the carotid-femoral pulse wave velocity (PWV);b)perfusion boundary region (PBR- micrometers) of the sublingual arterial microvessels as a marker of endothelial glycocalyx thickness;c) plasma malondialdehyde (MDA),NOx, and IL-6 levels as biomarkers of oxidative stress and inflammation.

Results:
The single cuff inflation protocol resulted in a more uniform aortic elasticity improvement (PWV T0: 12.09m/s, T1:11.74m/s, T2:11.59m/s, T3:11.81m/s),with the greatest difference measured at the last vascular assessment (T3: PWV= 11.8 single cuff vs 13.8 m/s double cuff inflation,p<0.05).A greater glycocalyx integrity restoration was observed in patients with baseline PBR> 2.1 in both protocols (mean difference in PBR improvement=0.5 at T1, p<0.001).Conversely,in healthy controls, PWV and PBR remained unchanged throughout the study (p>0.05).MDA was significantly reduced at T3 compared to baseline in STEMI(2.1 ± 0.15 at T3 vs 2.59 ±0.15 at T0, p< 0.001) in both protocols while it remained unchanged in healthy controls. Additionally, the single cuff inflation protocol promoted a greater increase in NOx levels compared to the double inflation protocol (T0: 8.25± 1.18 to T3: 11.1 ± 2 μμ vs T0: 10.79± 1.18 to T3: 8.91±2 μμ, p< 0.05). IL-6 levels were unaffected.

Conclusion:
Remote ischemic conditioning by a single 5-min cuff inflation, confers acute short-term improvement of vascular function, likely through oxidative stress reduction and nitrate- nitrite- NO pathway activation.
Abstract 11869: Identification of Human Lysophosphatidylcholine Acyltransferase 3 as a Novel Target Gene Regulated by Peroxisome Proliferator-activated Receptor Delta in Hepatic Cells and in Liver Tissue
Authors: Singh Amar B , Liu Jingwen
Published: April 2024

Peroxisome proliferator-activated receptor delta (PPARD) is a transcription factor regulating many important genes involved in lipid and glucose metabolism. Hepatic lysophosphatidylcholine acyltransferase 3 (LPCAT3) plays critical functions in TG secretion and ER stress response due to its unique ability to catalyze the incorporation of polyunsaturated fatty acids into phospholipids. Previous studies identified liver X receptor as the transcription factor controlling LPCAT3 expression in liver tissue. Here we showed for the first time that the hepatic LPCAT3 gene is transcriptionally regulated by PPARD
in vitro
and
in vivo
. Treatments of HepG2, Huh-7, and Hepa 1-6 cells with PPARD specific agonists (L-165041 and GW0742) increased LPCAT3 mRNA levels 2-3 fold of control. Adenovirus-mediated knockdown of PPARD in HepG2 cells reduced the basal level of LPCAT3 mRNA by approximately 40% compared to control and further attenuated the induction of PPARD agonist on LPCAT3 gene expression. To demonstrate the direct regulation of PPARD on LPCAT3 gene transcription, we analyzed human LPCAT3 promoter sequence and identified two putative PPAR responsive elements (PPRE-1, -171; PPRE-2, -727) within 1 kb of the proximal LPCAT3 promoter. LPCAT3 promoter assays demonstrated strong inductions of the reporter activity by PPARD agonists. Mutational analysis of the human LPCAT3 promoter revealed that the PPRE-1 is involved in conferring responsiveness to PPARD agonist mediated transcriptional activity. Direct binding of PPARD to PPRE-1 sequence was demonstrated by chromatin immunoprecipitation and gel retardation assays. Finally, we provided
in vivo
evidence showing that activation of PPARD by L-165041 in mice increased LPCAT3 mRNA abundance in the liver. Altogether, these new findings identify LPCAT3 as a direct PPARD target gene and suggest a novel function of PPARD in regulation of phospholipid metabolism through LPCAT3.
Abstract 11916: Circulating Concentrations of Orexin A Predict Left Ventricular Myocardial Remodeling
Authors: Ibrahim Nasrien E , Rabideau Dustin J , Gaggin Hanna K , Belcher Arianna M , Conrad Michael J , Jarolim Petr , Januzzi James L
Published: April 2024

Introduction:
Left ventricular reverse remodeling (LVRR) may occur with guideline directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF); LVRR is associated with better outcome in this setting. Molecular factors predictive of LVRR are not well understood.

Background:
Recent data suggest the minor allele for rs7767652 (upstream to the hypocretin/orexin receptor-2 [
HCRTR2
] gene) is inversely associated with likelihood for LVRR after GDMT. Infusion of orexin A (the HCRTR2 receptor ligand) was protective against LV remodeling.

Hypothesis:
Concentrations of circulating orexin A predict LV remodeling in HFrEF (left ventricular ejection fraction [LVEF] <40%) patients treated with GDMT.

Methods:
We measured concentrations of orexin A in 113 HFrEF patients at baseline and at 10 months. Patients underwent echocardiography at the same time points. Measures of LV remodeling included LV end-diastolic and end-systolic volume index (LVEDVi, LVESVi) and LVEF.

Results:
As a function of the median baseline orexin A concentration of 1.04 ng/mL, there was no difference between groups in baseline characteristics, and no difference in concentrations of other prognostic biomarkers. Subjects with baseline orexin A ≥ 1.04 ng/mL had significantly greater reduction in LVEDVi and LVESVi and a trend towards greater improvement in LVEF at 10 months. Significantly fewer subjects with a baseline Orexin A concentration ≥ 1.04 ng/mL had increase in LVEDVi or LVESVi at study completion (
Table
). In binomial regression adjusted for age, gender, and baseline LV volumes, subjects with a baseline orexin A ≥ 1.04 ng/mL were less likely to have increase in LVEDVi (relative risk [RR] 0.51; 95% confidence interval [CI]: 0.30-0.84, P = 0.007) or LVESVi (RR 0.49; 95% CI: 0.28-0.85, P = 0.01). Follow up orexin concentrations did not add to baseline values for predicting LVRR.

Conclusions:
Orexin A is a unique prognostic biomarker for myocardial remodeling in chronic HFrEF.
Abstract 11928: Galectin-3 is Associated With Adverse Cardiovascular Outcomes in Asymptomatic Individuals in the Atherosclerosis Risk In Communities (ARIC) Study
Authors: Aguilar David , Nambi Vijay , Sun Wensheng , Selvin Elizabeth , Matsushita Kunihiro , McEvoy John W , Shah Amil M , Solomon Scott D , Boerwinkle Eric , Ballantyne Christie M
Published: April 2024

Introduction:
Although galectin-3, an indicator of myocardial fibrosis, provides prognostic value in patients with established heart failure, its prognostic significance in a diverse, asymptomatic population is largely uncharacterized.

Objectives:
We measured plasma galectin-3 in 9255 individuals free of cardiovascular disease at baseline (visit 4, 1996-1998) and evaluated prospective associations with incident coronary heart disease (CHD), heart failure (HF) hospitalization, ischemic stroke, or total mortality in the biracial Atherosclerosis Risk in Communities (ARIC) study.

Methods:
Outcome incident rates were expressed as number of events per 1,000 patient years. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals for the association of quartiles of galectin-3 with each outcome. The models were adjusted for age, gender, race, total cholesterol, HDL cholesterol, SBP, anti-hypertensive medication, current smoking, diabetes status, estimated GFR, and log NT-proBNP. Interactions for race and sex were ascertained by adding a cross-product of race or sex and galectin-3 in the model.

Results:
In the adjusted model, increasing quartiles of galectin-3 were independently associated with incident CHD, HF, and mortality (
Table
), with the highest HR for HF. The relationship was not significantly modified by gender or race, except for CHD where galectin-3 was associated with increased risk in whites but not blacks (interaction p=0.04). Galectin-3 quartiles were not associated with incident stroke in adjusted analysis.

Conclusion:
In a large, bi-racial cohort of individuals free of CVD at baseline, galectin-3 is associated with increased risk of incident CHD, HF, and death. These data implicate myocardial fibrosis in the development of CVD in a community-based population of black and white adults.
Abstract 11969: Survival From Out-of-Hospital Cardiac Arrest: Intravenous Versus Intraosseous Resuscitation
Authors: Feinstein Bryan A , Stubbs Benjamin , Kudenchuk Peter J
Published: April 2024

Background:
Although administration of drugs by intraosseous vascular access during out-of-hospital cardiac arrest (OHCA) is growing in popularity and prevalence, the actual effectiveness of this treatment approach is uncertain.

Hypothesis:
We hypothesized that there would be no difference in resuscitation outcome as measured by survival to hospital discharge after OHCA based on the mode of drug delivery.

Methods:
We performed a retrospective cohort study of emergency medical services (EMS)-treated, non-traumatic OHCA among persons >18 years of age in King County, WA (excluding Seattle) between September 1, 2012 through December 31, 2014. Patients were classified as IV or IO treatment recipients based on the route of first drug administered during OHCA. Study outcomes were analyzed by multivariate logistic regression. The primary outcome investigated was survival to hospital discharge. Secondary outcomes measured were sustained return of spontaneous circulation (ROSC) and survival to hospital admission.

Results:
Among 1241 adults with OHCA in whom the time to vascular access was known, 1021 were treated via IV and 220 via IO routes. Patients comprising the IO group were younger, included more women, were more likely to have had an unwitnessed OHCA, an arrest of non-cardiac etiology and less likely to have a shockable initial rhythm than IV patients. IO drug recipients were less likely to achieve sustained ROSC, survive to hospital admission or survive to hospital discharge than the IV group. In adjusted analyses, compared to the IV group, recipients of IO medications were less likely to achieve sustained ROSC (odds ratio (95% confidence interval (CI) 0.69 (0.5, 0.95), p = 0.02) with a trend toward a lower likelihood of being admitted alive to hospital (odds ratio (95% CI) 0.72 (0.52, 1.01), p = 0.06), but there were no differences between the two groups in survival to discharge (odds ratio (95% CI) 0.87 (0.54, 1.40), p = 0.56).

Conclusion:
IO as compared with IV access is independently associated with a lower likelihood of achieving sustained ROSC after OHCA and a trend toward decreased hospital admission, but not survival to hospital discharge.
Abstract 11974: Sestrin2 Prevents Age-related Intolerance to Ischemia and Reperfusion Injury via Modulating Substrate Metabolism
Authors: Quan Nanhu , Wang Lin , Chu Dongyang , Chen Xu , Cates Courtney , Liu Quan , Zheng Yang , Li Ji
Published: April 2024

Introduction:
A novel stress-inducible protein, Sestrin2, declines in the heart with aging. AMP-activated Protein Kinase (AMPK) has emerged as a pertinent stress-activated kinase shown to have cardioprotective capabilities against myocardial ischemic injury. We identified the interaction between Sestrin2 and AMPK in the ischemic heart.

Hypothesis:
The ischemic AMPK activation modulated by Sestrin2-AMPK complex in the heart is impaired in aging that sensitizes heart to ischemic insults.

Methods:
C57BL/6 young mice (4-6 months), middle age mice (10-12 months) and aged mice (24-26 months) were subjected to left anterior descending coronary artery occlusion for
in vivo
regional ischemia. The
ex vivo
working heart system was used for measuring substrate metabolism.

Results:
The protein level of Sestrin2 in the hearts were gradually decreased with aging. Intriguingly, ischemic AMPK activation was blunted in the aged hearts as compared with young hearts (p<0.05), the AMPK downstream glucose uptake and the rate of glucose oxidation were significantly impaired in the aged hearts during ischemia and reperfusion (I/R) (p<0.05
vs.
young hearts). The myocardial infarction size was larger in the aged hearts (p<0.05
vs.
young hearts). The immunoprecipitation with Sestrin2 antibody revealed that cardiac Sestrin2 forms a complex with AMPK and upstream LKB1 during ischemia, intriguingly, the binding affinity between Sestrin2 and AMPK upstream LKB1 is impaired in the aged hearts during ischemia (p<0.05
vs.
young hearts). Furthermore, Sestrin2 knock out hearts demonstrate a similar cardiac phenotype and response to ischemic stress as the wild type aged hearts, i.e. impaired ischemic AMPK activation and higher sensitivity to I/R-induced injury. Adeno-associated virus 1 (AAV1)-Sestrin2 were delivered into the aged hearts
via
a coronary delivery approach significantly rescued the protein level of Sestrin2 and the ischemic tolerance of aged hearts.

Conclusions:
Sestrin2 is a scaffold protein that mediates AMPK activation in the ischemic myocardium
via
an interaction with AMPK upstream LKB1. The decreased Sestrin2 levels in aging lead to a blunted ischemic AMPK activation, alterations in substrate metabolism and an increased sensitivity to ischemic insults.
Abstract 12031: Initiation, Continuation, or Withdrawal of Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers and Outcomes in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction
Authors: Gilstrap Lauren G , Fonawow Gregg C , Li Liang , DeVore Adam , Smith Eric E , Heidenreich Paul , Hernandez Adrian F , Yancy Clyde W , Bhatt Deepak L
Published: April 2024

Background:
Guidelines recommend continuation or initiation of treatment with angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARB) in hospitalized patients with heart failure with reduced ejection fraction (HFrEF).

Methods:
Using data from Get With The Guidelines-Heart Failure, we linked 16,052 HFrEF patients with Medicare claims. We divided patients into 4 categories based on admission and discharge ACEi/ARB use: continued, started, discontinued, or not started. A multivariable Cox proportional hazard model was performed to determine the association between the categories and 30-day, 90-day and 1-year outcomes.

Results:
A total of 90.6% of patients were discharged on ACEi/ARB (59.6% continued, 30.9% started, 1.9% discontinued, 7.5% not started). The 30-day mortality rate was higher, 8.8% for those discontinued (HR
adj
2.04; 95% CI 1.42, 2.92; P<0.001) and 7.5% for those not started (HR
adj
1.55; 95% CI 1.16, 2.07, P=0.003), compared with 3.5% for those continued on ACEi/ARB. There was no significant difference in 30-day mortality between those continued and those started. The 30-day readmission rate was higher, 28.6% for those discontinued (HR
adj
1.44; 95% CI 1.19, 1.75; P<0.001) and 23.3% for those not started (HR
adj
1.17, 95% CI 1.03, 1.32, P=0.013), compared with 18.3% for those continued on ACEi/ARB. Again, there was no significant difference in 30-day readmissions between those continued and those started. By one year, the mortality rate was lowest among those continued on ACEi/ARB compared to those discontinued (HR
adj
1.42; 95% CI 1.18, 1.70, P<0.001) or not started (HR
adj
1.32, 95% CI 1.18, 1.47, P<0.001).

Conclusions:
Initiation or continuation of ACEi/ARB therapy after an admission with HFrEF is associated with lower 30-day mortality and readmission rates. The lower mortality associated with continuing ACEi/ARB therapy persists out to 1 year.