bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16643: Very Low LDL Cholesterol Level Below 50mg/dL is Not Harmful for Patients Underwent Percutaneous Coronary Intervention in Drug Eluting Stent Era
Authors: Kang Min-Kyu , Chin Jung Yeon , Yi Jung Yeon , Hwang Byung-Hee , Kim Tae-Seok , Kim Chan Joon , Seung Ki-Bae , Chung Wook Sung , Chang Kiyuk , Kim Pum Joon , Park Hun-Jun , Koh Yoon-Seok , Seo Suk Min , Choo Eun Ho , Ann Soe Hee
Published: April 2024

Introduction
There has been the paucity of data for the safety of very low LDL-cholesterol level below 50 mg/dL in patients with coronary artery disease who underwent percutaneous coronary intervention.

Hypothesis
Very low LDL-C level may be safe in patients underwent PCI in terms of major adverse cardiac event including death, nonfatal myocardial infarction, stroke or revascularization of any cause.

Methods
We analyzed a total 9,292 consecutive patients who underwent PCI using drug eluting stent from January 2004 to December 2009. Among these, 2704 subjects who had initial and follow-up lipid panel and attained low LDL-cholesterol (LDL-C<100mg/dL) with statin therapy were enrolled. Median follow up period was 28.3 months (interquartile range 15.1, 41.5 months). Laboratory study was performed at the time of index drug-eluting stent implantation and at the outpatient visit between three and twelve months later. We categorized patients into three groups based on the follow-up LDL-cholesterol level : <50, 50 to 70, 71 to 100 mg/dL(n=399, 1028, 1277, respectively). We compared major adverse cardiac events including all-cause death, nonfatal myocardial infarction, stroke and revascularization of any cause according to the follow up LDL-cholesterol group.

Results
Multivariable Cox regression analysis revealed that in the patients with well controlled follow up LDL-C level (LDL<100 mg/dL), multivessel disease, presence of angiographic AHA/B2C lesion were strongly associated with increase in a hazard ratio of a composite of death, myocardial infarction, strtoke and revascularization of any cause. But LDL-C was not associated with the occurrence of MACEs. (Table 1.)

Conclusions
In patients who underwent PCI with DES and well controlled LDL level, cholesterol paradox is not observed. It may be safe in patients with very low LDL-C level below 50 mg/dL in spite of continuous use of statin in terms of MACEs. Keywords lipoprotein, hyperlipidemia, coronary heart disease, PCI
Abstract 16646: The Novel Hydrogen Sulfide Donor Diallyl Trisulfide Protects Against Ischemia-Reperfusion Injury by Inhibition of Mitochondrial Respiration
Authors: Predmore Benjamin , Bhushan Shashi , Aragon Juan Pablo , Grinsfelder Bennette , King Adrienne , Calvert John , Condit Marah , Lefer David
Published: April 2024

Hydrogen sulfide (H2S) is enzymatically produced in the body, and has a range of cardioprotective effects including: anti-inflammatory, antioxidant, and anti-apoptotic actions, and inhibition of mitochondrial respiration. However, because of its volatile and reactive nature, H2S remains a challenge to administer therapeutically. In this study we investigate the novel, stable H2S donor diallyl trisulfide (DATS) in an in vivo murine model of myocardial ischemia-reperfusion (MI/R) injury, as well as on mitochondrial respiration in isolated murine mitochondria. Mice (C57BL6/J, 8-10 wk old) were subjected to 45 minutes of myocardial ischemia followed by reperfusion for 24 hr. DATS or vehicle was administered just prior to reperfusion. At 24 hr of reperfusion, infarction per area-at-risk (INF/AAR) was evaluated with Evan's Blue dye and 2,3,5-tetrazolium chloride staining and serum was collected for Troponin-I measurement with a commercial kit. Cardiac mitochondria were isolated from a separate group of mice and State 3 respiration was determined in the presence or absence of DATS. H2S release from DATS was determined using a polarographic H2S electrode. DATS (200 µg/kg) reduced the INF/AAR by 61% (p<0.001 vs. Vehicle). DATS also reduced circulating troponin-I levels from 43.58±5.7 ng/mL to 16.38±5.0 ng/mL (p=0.003 vs. Vehicle). Application of DATS to isolated mitochondria resulted in a release of H2S at a rate of 0.91+/-0.19 pmol/min. Mitochondrial State 3 respiration significantly decreased 70% by the addition of 200 µM DATS (p<0.001 vs. Control). Taken together, these data demonstrate that DATS is an effective H2S donor, which significantly reduces infarct size following MI/R injury, potentially by inhibition of mitochondrial respiration.
Abstract 16654: Sizing Strategy is a Major Determinant for Postoperative Pressure Gradients in Commonly Implanted Stented Tissue Valves
Authors: Diab Mahmoud A , Peter Jack , Faerber Gloria , Bothe Wolfgang , Lemke Susanne , Breuer Martin , Breuer Martin , Doenst Torsten
Published: April 2024

Background
Heated debates revolve around hemodynamic performance of stented tissue valves. We and others reported differences in valve size nomenclature confusing direct comparisons. Relative valve opening has been suggested to be improved by designing pericardial valves with stents on the outside (Perimount), or the inside (Mitroflow) of the valve, but the sizing strategies and sizer dimensions are also different. We reviewed hemodynamics of our patients having received aortic valve replacement (AVR) with the the Edwards Perimount or the Sorin Mitroflow, both valves, where size selection was based on intra-annular sizing. We speculated that differences in sizing strategy may be more important than differences in valve design.

Methods
We analyzed discharge echos (performed by the same examiner) from all patients having received a Perimount (n=521) or a Mitroflow (n=157) between 01/2007 and 11/2010. We obtained valve outer diameters from the manufacturers, and measured sizer dimensions with a calliper. We compared mean gradients (ΔP) and maximum velocity across the valve (Vmax) based on size label, outer diameter, or selected size based on suggested sizing strategy.

Results
The majority of implanted valves were size 23 (n=259). Their outer diameters were 31mm for Perimount, and 26mm for Mitroflow. Despite the smaller outer diameter, the lowest gradients were found in the Mitroflow: ΔP 11.72±4.18 mmHg (Vmax 2.31±0.38 m/s) vs Perimount: ΔP 12.85±4.29 mmHg (Vmax 2.41± 0.34 m/s) p<0.05, suggesting a design advantage. However, the 23 Mitroflow sizer was 25mm and the 21sizer was 23mm. In contrast, the 23 Perimount sizer was indeed 23mm. Thus, an intrannular sizing strategy for a patient with a 23 mm annulus will result in the selection of a 21 Mitroflow but a 23 Perimount. Hemodynamic comparison of the 21 Mitroflow with the 23 Perimount eliminated the above described differences (21 Mitroflow: ΔP 13.5 ± 5.4 mmHg (Vmax 2.52 ± 0.25 m/s).

Conclusion
The potential hemodynamic advantage of the Mitroflow may be lost due to a “defensive” sizing strategy. The results underscore the importance of sizing strategy and surgical technique and supports the provision of replica sizers with the new generation valves.
Abstract 16661: Impact of the Learning Curve on Outcome After Transcatheter Mitral Valve Repair: First Results From the German Mitral Valve Registry
Authors: Ledwoch Jakob , Teufel Tobias , Wunderlich Nina , Franke Jennifer , Bertog Stefan , Baldus Stephan , Wachter Rolf , Schäfer Ulrich , Hehrlein Christoph , Möllmann Helge , Müller Ralf , Ouarrak Taoufik , Deeg Evelyn , Senges Jochen , Sievert Horst
Published: April 2024

INTRODUCTION:
Catheter-based treatment of mitral regurgitation (MR) has increasingly been used as an alternative treatment option to surgery. New complex catheter-based techniques are frequently subject to a steep learning curve.

PURPOSE:
Evaluation of the impact of growing operator experience with percutaneous mitral repair on procedural success and complications.

METHODS:
This is an analysis of patients in the German Mitral Valve Registry who underwent percutaneous mitral valve repair for MR. Consecutive patients treated since 2009 in centers that performed more than 20 transcatheter mitral repairs were included. Results of the first half of the patients were compared to those of the second among centers that treated less than 30 patients. Among centers with more than 30 patients results of the first 15 patients were compared to those of the last 15 patients. Primary endpoint was hospital death; secondary endpoints were postprocedural complications and 30-day mortality.

RESULTS:
181 patients from 6 centers were included. There was no significant difference in baseline characteristics, NYHA grade and MR severity between the first and last patients. In almost all procedures the MitraClip® device (97.2%) was used. The EuroSCORE was 27.0% in patients treated first vs. 19.0% in patients treated later (p= 0.05). Procedural success was 94.3% (83/88) in the first cases and 94.6% (87/92) subsequently. There was no significant difference in hospital (3.4% vs. 1.2%, p= 0.32) or 30-day mortality (14.0% vs. 11.9%; p=0.78) between patients treated first compared to those treated subsequently. However, postprocedural complications were significantly higher in patients treated first compared to those treated later (24.4% vs. 10.7%, p< 0.05) largely related to vascular access (serious bleeding 8% vs. 0%).

CONCLUSION:
A learning curve using a catheter-based approach to treat MR does not appear to affect the procedural success or 30-day and perioperative mortality. However, it does have a significant impact on the rate of postprocedural complications, mainly related to vascular access.
Abstract 16712: Focal Adhesion Kinase: A Putative Therapeutic Target for the Treatment of Pulmonary Arterial Hypertension
Authors: Paulin Roxane , Meloche Jolyane , Courboulin Audrey , Lambert Caroline , Michelakis Evangelos , Bonnet Sebastien
Published: April 2024

Background:
Pulmonary arterial hypertension (PAH) is characterized by enhanced pulmonary artery smooth muscle cells (PASMC) proliferation, migration and suppressed apoptosis. This phenotype is attributed in part to the sustained activation of the neoplasic axis c-Src/STAT3. In cancer, c-Src enhances focal adhesion kinase activation (FAK), a signaling hub implicated in the sustainability of cell proliferation, survival and motility, in part by potently inducing STAT family of proteins activation. Recently FAK inhibition has been proposed as a new therapeutic intervention in cancer. We hypothesized that FAK inhibition in PAH will decrease the activation of STAT3 axis decreasing PASMC proliferation, migration and resistance to apoptosis.

Methods/Results:
Using immunoblots (n=3 p<0.05) we showed activation of both c-Src and FAK (phosphorylation on Y416 and Y397 respectively) in human PAH-PASMCs resulting in cSrc/FAK complex formation (FAK phosphorylation on Y576) promoting STAT3 activation (phosphorylation on Y705). All these results were inhibited by 1) Src inhibitor PP2, 2) FAK siRNA. The Src/FAK-dependent activation of STAT3 accounts for 1) PAH-PASMCs mitochondrial hyperpolarization (TMRM n=150 p<0.05), increasing resistance to apoptosis (n=150 p<0.05 TUNEL) 2) increases proliferation by 30% (PCNA & Ki67) 3) increases cell migration (transwell assay, n=3 p<0.05) and invasion (Scratch test n=5 p<0.05) by 25% compared to controls. All these findings were similarly reversed by either Src, FAK and STAT3 inhibitors. Finally, in vivo FAK-siRNA nebulization improves monocrotaline-PAH (n=10 in each group p<0.05) measured by PA pressure, PA wall thickness, right ventricular hypertrophy (Echo & catheterization).

Conclusion:
FAK inhibition represents a new therapeutic target for PAH. Currently new FAK inhibitors have been moved to clinic trials to treat cancer. Our findings suggest that these compounds could be useful for the treatment of PAH as well.
Abstract 16715: Anatomical Data Defined by 64-Slice CT Angiography Predicts Prognosis of Coronary Artery by-Pass Patients More Accurately That Clinical Risk Predictors
Authors: Small Gary R , Yam Yeung , Chen Li , Ahmed Osman , Al-Mallah Mouaz , Berman Daniel S , Cheng Victor Y , Chinnaiyan Kavitha , Raff Gilbert L , Villines Todd C , Achenbach Stephan , Budoff Matthew J , Cademartiri Filippo , Callister Tracy Q , Chang Hyuk-Jae , Delago Augustin , Dunning Allison , Hadamitzky Martin , Hausleiter Jörg , Kaufmann Philipp , Lin Fay Y , Maffei Erica , Min James K , Shaw Leslee J , Chow Benjamin J
Published: April 2024

Objective:
We sought to determine the incremental prognostic value of 64 multi-slice coronary computed tomography angiography (CCTA) in coronary artery bypass (CABG) patients.

Background:
Prognostication in CABG patients can be difficult. Anatomical assessment of native coronary artery disease and graft patency may provide useful information, but the utility of CCTA in the assessment of CABG patients is unknown.

Methods:
657 CABG patients with all cause mortality follow up were identified from a multicenter CCTA registry, of 10,628 patients from 5 CCTA centres. Clinical risk was profiled with modified logistic and additive EuroSCOREs. CCTA defined coronary anatomy. Patients were classified by unprotected coronary territory (UCT), or a summary of native vessel disease and graft patency: the coronary artery protection score (CAPS).

Results:
76.6% of patients were male and the median age was 68 years. 44 deaths occurred over 48 months follow-up. LVEF, creatinine, age, severity of native vessel disease, UCT, CAPS and EuroSCOREs were univariate predictors of mortality (p<0.001). In multivariate analysis using additive EuroSCORE, UCT (p=0.004) and CAPS were predictive of events (p<0.001). In comparison to additive EuroSCORE, CAPS score was associated with a 27% net reclassification index.

Conclusions:
CCTA provides incremental anatomical data to clinical risk assessment to better determine the prognosis of symptomatic patients post CABG. CAPS evaluation using CCTA may help determine those patients at highest risk.
Abstract 16720: Induction of Notch Activity Promotes a Cardiac Differentiated Phenotype in Adult Cardiac Progenitor Cells
Authors: Gude Natalie A , Fischer Kimberlee , Truffa Silvia , Bailey Brandi , Avitabile Daniele , Joyo Anya , Joyo Eri , Sussman Mark A
Published: April 2024

Introduction:
Notch is a critical mediator of heart development, stem cell self-renewal and specification; appropriate timing and levels of Notch signaling are essential for proper cell fate determination. However, constitutive activation of Notch does not recapitulate the physiological signal driving cardiac differentiation.

Hypothesis:
Controlled pulses of Notch activation enhance cardiac differentiation in CPCs.

Methods:
Ligand-regulated or tetracycline inducible versions of intracellular Notch designed to control timing and activation level were engineered into cultured adult cardiac progenitor cells (CPCs). Stable CPC lines were created carrying constructs for GFP (CPCe), ligand-regulated intracellular Notch (CPCeK), or tetracycline inducible intracellular Notch (CPCtetKmER). Induction was performed using 1 µM tamoxifen and/or 1 µM doxycycline with proliferation measured over a period of 6 days. Markers of Notch signaling and cardiac differentiation were assessed by quantitative PCR, immunoblotting, or immunostaining up to 6 days after induction.

Results:
Increased levels of hey1, jagged1, cardiac troponin T (cTnT) and smooth muscle actin (SMA) transcripts were observed following one day of Notch induction in CPCeK and CPCtetKmER. Changes indicative of differentiation were present in CPCeKs and CPCtetKmERs following one week after Notch induction including flattened and enlarged morphology, elevated levels of smooth muscle actin (SMA) and jagged1 mRNA, and expression of SMA protein. Proliferation decreased after three days of sustained Notch signaling.

Conclusions:
Notch signaling promotes CPCs to acquire phenotypic characteristics of smooth muscle or myocyte differentiation. Engineering CPCs allows for appropriate “physiologic” temporal control to regulate the potent cardiogenic activity of Notch signaling. Regulation of Notch activity in CPCs utilizing temporal and reversible expression will enhance commitment and differentiation when utilized in conjunction with cell based therapy for heart disease, thereby enhancing myocardial regeneration and repair.
Abstract 16740: Intracoronary versus Intravenous Administration of GP IIb/IIIa Inhibitors During Percutaneous Coronary Intervention for Acute Coronary Syndromes: A Meta-Analysis of Randomized Controlled Trials
Authors: Friedland Sayuri , Eisenberg Mark J , Shimony Avi
Published: April 2024

Background:
It is unclear whether intracoronary (IC) bolus administration of glycoprotein IIb/IIIa inhibitors (GPIs) is superior to intravenous (IV) administration during percutaneous coronary intervention (PCI) in patients with acute coronary syndromes (ACS). We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of IC and IV administration.

Methods and Results:
We systematically searched the Cochrane library, EMBASE, and MEDLINE databases for RCTs comparing IC and IV administration of GPIs (abciximab, eptifibatide, tirofiban) during PCI. Data were pooled using random-effects models and stratified into short (1-3 months) and mid/long-term (≥6 months) follow-up durations. Ten RCTs involving 1,590 patients met our inclusion criteria. Seven of the 10 RCTs included only patients with STEMI; in the other 3 studies, the percentage of patients presenting with STEMI ranged from 26% to 63%. Within each study, the dose and duration of GPI administration was identical in the IC and IV groups. Compared to the IV group, the IC group was more likely to have complete perfusion (TIMI 3 flow) post-PCI (relative risk [RR] 1.08, 95% confidence interval [CI] 1.02, 1.15). IC administration was associated with similar bleeding rates as IV (RR 0.91, 95% CI 0.67, 1.24), but with a significant reduction in short-term target vessel revascularization (TVR) (RR 0.55, 95% CI 0.30, 0.99). IC administration was also associated with a significant reduction in short-term mortality (RR 0.49, 95% CI 0.24, 0.99), but this reduction was no longer significant in mid/long term RCTs.

Conclusions:
Compared to IV, IC bolus administration of GPIs has favorable effects on post-PCI TIMI flow, TVR, and short-term mortality, with similar rates of bleeding. Data regarding mid/long term outcomes were limited and inconclusive. Large RCTs with longer follow-up are required to determine long-term safety and efficacy.
Abstract 16743: Hyperphosphatemia and Hypozincemia Aggravated Hypertension and Cardiac Dysfunction in SHR/NDmcr-cp, a Model of Metabolic Syndrome
Authors: Suzuki Yuka , Yamaguchi Takanori , Kato Ai , Ichihara Gaku , Ichihara Sahoko
Published: April 2024

Background:
It is known that metabolic syndrome affects cardiac function. Given that patients with diabetic nephropathy easily suffer from hyperphosphatemia and hypozincemia and obesity also induces higher phosphorus and lower zinc levels in plasma, we investigated whether the higher phosphorus and lower zinc levels in plasma affect cardiovascular system using SHR/NDmcr-cp, a rat model of metabolic syndrome. We also investigated the effects of antioxidant, N-acetyl-L-cysteine (NAC), on the development of cardiac dysfunction under the above conditions.

Methods & Results:
Male SHR/NDmcr-cp and control (WKY) rats were divided into 3 groups and were fed control diet (P 0.3% w/w, Zn 0.2% w/w) or a high-phosphorus and zinc-deficient (P 1.2 % w/w, Zn 0.0 % w/w) diet. The latter group was treated with either NAC (1.5 mg/g per day) or vehicle from 8 to 12 weeks of age (n = 6 or 8 for each group). The systolic blood pressure was increased by high-phosphate and zinc-deficient diet in both the SHR/NDmcr-cp and the WKY. NAC treatment improved these changes. The echocardiographic data elucidated that left ventricular (LV) systolic and diastolic function was markedly reduced in the SHR/NDmcr-cp by high-phosphate and zinc-deficient diet and only LV diastolic function was reduced in the WKY by the same diets. The high-phosphate and zinc-deficient diet significantly induced fibrosis of myocardium in the SHR/NDmcr-cp pathologically, and this change was improved by NAC. Treatment with NAC prevented diastolic dysfunction in WKY, but in SHR/NDmcr-cp it could only improve systolic function but did not recover diastolic function.

Conclusion:
Dietary high phosphorus and deficiency of zinc induced cardiac dysfunction in rats. Cardiac dysfunction resisted against the protective effects by NAC in the rat model of metabolic syndrome.
Abstract 16745: Usefulness of Analysis of Transthoracic Impedance Signals for Accurate Diagnosis of Sleep Disordered Breathing in Patients with Permanent Pacemaker Implantation
Authors: Miyamoto Shoichi , Fujita Masatoshi , Ishimura Takao , Inoko Moriaki , Haruna Tetsuya , Izumi Toshiaki , Katoh Takao , Nakane Eisaku , Saji Yosiaki , U eyama Koji , Nohara Ryuji
Published: April 2024

Purpose:
There are several reports regarding an excessively high prevalence of undiagnosed sleep disordered breathing (SDB) in patients with permanent pacemaker implantation. Some programs for pacemakers utilize transthoracic impedance changes between the generator and the electrode tip to derive minute ventilation as a sensor for rate adaptation. We investigated whether this system can detect sleep-related breathing disorders.

Methods:
We investigated 39 patients (19 male, 20 female, 78±13 (SD) years) who underwent permanent pacemaker implantation for sick sinus syndrome and advanced or complete atrio-ventricular nodal block. Body mass index of these patients was 23±4 kg/m
2
. Chronic heart failure was observed in 10 (26%) of 39 patients. We measured the number of the transthoracic impedance signals remaining unchanged for more than 10 seconds with use of the pacemaker minute ventilation sensor (SORIN), and compared with the results of polysomnography (Morpheus C, Teijin). By using polysomnography, we calculated the number of apnea/hypopnea episode per hour (apnea/hypopnea index: AHI). We defined the number of respiratory cycles more than 10 seconds of unchanged transthoracic impedance signals as the respiratory disturbance index (RDI). Receiver operating characteristic (ROC) analysis was performed on the RDI for the diagnosis of moderate to severe SDB (AHI >20).

Results:
Moderate to severe SDB was diagnosed in 18 (46%) of 39 patients. The area under the ROC curve was 0.87 (95% CI 0.75 to 0.99). Given a cutoff value of 210/hour for the RDI, the RDI can significantly (p<0.05) discriminate between patients with and without moderate to severe SDB, and showed 72.2% sensitivity and 90.5% specificity for the diagnosis. The RDI was well correlated with the AHI in patients with moderate to severe SDB (n=15, r=0.771, p=0.0004).

Conclusions:
Detection of apnea/hypopnea episode by pacemaker minute ventilation sensor is feasible and accurate for diagnosing SDB in patients with permanent pacemaker implantation.
Abstract 16765: Clinical Outcomes and Thromboembolic Complications Related to Recombinant Factor VII Activated Use for Refractory Medical Bleeding After Pediatric Cardiac Surgery
Authors: Troncone Michael J , Brandao Leonardo R , Caldarone Christopher A , Manlhiot Cedric , McCrindle Brian W , Schwartz Steven M , Van Arsdell Glen , Sivarajan V B
Published: April 2024

Introduction:
Resolution of refractory bleeding after cardiac surgery with Recombinant Factor VII activated (rFVIIa) has been demonstrated. Increased use for this indication and resultant thromboembolic complications (TCs) have been described.

Hypothesis:
rFVIIa use after pediatric cardiac surgery reduces postoperative bleeding without increasing the risk of TCs or death.

Methodology:
A matched case-control analysis of pediatric inpatients from 2004-2009 was performed. Cases received rFVIIa intraoperatively or in the intensive care unit after cardiac surgery. Cases were matched 1:1 to controls by age and operation. Demographic and perioperative clinical variables were collected. Primary outcomes of interest were death or TCs; secondary outcomes were blood product utilization, chest tube drainage, duration of ventilation and length of stay. TCs were defined as intravascular thrombosis (venous, arterial, intracardiac), cardioembolic stroke or pulmonary embolism confirmed by radiologic methods, surgery, catheterization or autopsy performed at any point after the index operation.

Results:
50 cases were reviewed; cases had median weight at operation of 6 kg. Index operations for which rFVIIa was given included single ventricle palliations(26%) and heart transplantation(24%). Cases had longer cardiopulmonary bypass (157 vs 124 minutes, p=0.003) time with greater postoperative red blood cell (13 vs 10 ml/kg; p=0.008) and platelet (29 vs 6 ml/kg; p=0.008) transfusion requirements. The median rFVIIa dose was 150 mcg/kg with thirty-six (72%) patients receiving it intraoperatively; bleeding reduced significantly after rFVIIa administration (10.5 vs 2.0 mL/kg/h; p=0.001). Cases had a longer duration of postoperative ventilation (4 vs 1.5 days, p=0.02) and hospital stay (19 vs 9 days, p=0.03). After rFVIIa use, rate of TCs (32 vs 26%, p=0.66) and mortality (32 vs 20%, p=0.25) were comparable to controls.

Conclusions:
rFVIIa dramatically reduces refractory bleeding after pediatric cardiac surgery; these patients still have increased blood product requirements and length of stay. There does not appear to be an incremental risk of TCs after rFVIIa administration. This may be reflective of the high burden of TCs in this population.
Abstract 16773: Exercise Tolerance and Vo2 Are Improved in Patients Undergoing Fontan Conversion with Arrhythmia Surgery
Authors: Tsao Sabrina , Webster Gregory , Ward Kendra , Franklin Wayne H , Deal Barbara J
Published: April 2024

Background:
Exercise tolerance in Fontan patients is known to decline with advancing age. The impact of improving right atrial flow dynamics and eliminating anti-arrhythmic medications on exercise tolerance is not known.

Hypothesis:
Successful Fontan conversion with arrhythmia surgery results in improvement in exercise tolerance over time.

Methods:
We reviewed data on patients who underwent Fontan conversion at our center since 1994. Fontan conversion surgery included arrhythmia surgery with pacemaker implantation. Exercise duration, peak HR, respiratory quotient, VO2, age at most recent exercise test and postoperative interval were recorded. Continuous variables were compared using two-tailed t-test method.

Results:
Fontan conversion with arrhythmia surgery has been performed on 132 pts at our institution. Pre-operative exercise testing was performed in 88 pts, with paired follow-up exercise data available on 29 pts. The mean age at Fontan conversion was 22.7 years. The mean interval from surgery to the most recent exercise stress test was 4.8 years (0.5-14.1 yrs). The mean exercise duration at baseline was 69% predicted for age and improved to a mean of 78% predicted for age at follow-up (p=0.02, mean duration in minutes: 6.9 at baseline, 8 at follow-up). The mean VO2 predicted for age improved from 53% to 64% (p<0.01, mean VO2 in ml/kg/min increased from 22.3 to 25.8) (see graph below for results). No significant change was seen in peak heart rate (148 vs 150 bpm, p=NS).

Conclusions:
In contrast to an expected decline in exercise tolerance with age in Fontan patients, successful Fontan conversion with arrhythmia surgery results in improvement in exercise endurance and oxygen consumption over a 5 yr follow-up period. Data was only available in a limited subset of patients undergoing Fontan conversion. These findings suggest that aggressive measures to improve hemodynamics in Fontan patients can result in improvement in functional status in adulthood.
Abstract 16774: Prenatal Diagnosis of Congenital Heart Disease and Association with Morbidity Among Survivors of Initial Palliation for Single Ventricle Heart Disease: Analysis of the National Pediatric Cardiology Quality Improvement Collaborative Database
Authors: Brown David W , O'Brien Patricia , Cohen Katie E , Gauvreau Kimberlee , Klitzner Thomas S , Beekman Robert H , Kugler John D , Martin Gerard R , Neish Steven R , Rosenthal Geoffrey L , Lannon Carole , Jenkins Kathy J ,   National Pediatric Cardiology Quality ImprovementCollaborative
Published: April 2024

Background:
Among infants with single ventricle congenital heart disease (SVD) requiring Stage I Norwood operation (S1P), the impact of prenatal diagnosis on outcomes has been variably characterized. We sought to further characterize this impact in a large multi-center cohort of survivors of S1P in the National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC).

Methods:
Retrospective analysis of demographic and outcomes data to time of Glenn operation (BDG) in infants enrolled in the NPC-QIC database; eligibility includes SVD requiring S1P and survival to hospital discharge.

Results:
From 31 contributing surgical centers, 195 infants were enrolled in the NPC-QIC database and had data available to time of BDG (177) or interstage death (18). Median gestational age was 39 weeks (32-41), 65% were male, 64% had variants of hypoplastic left heart syndrome, 8% had major syndromes, and 12% had major non-cardiac organ system anomalies. A prenatal diagnosis (PD) of SVD was made in 147 (75%) and did not vary by race or ethnicity. While infants with PD had slightly lower gestational age at birth (p<0.001) and lower age at S1P, there were no significant differences in birth weight, presence of major syndromes or other organ system anomalies, APGAR scores, lowest pH prior to post-natal intervention, age at intubation, or presence of pre-operative risk factors. Those without PD were more likely to have significant atrioventricular valve regurgitation (p=.03) and acidosis (p=0.02), although rates of ventricular dysfunction, pre-operative mechanical ventilation and shock were similar between groups. In multivariate analysis, length of intubation was not associated with PD, and hospital length of stay was the same between groups (26 days). Interstage readmissions and deaths were not associated with PD. At time of BDG, those with PD were slightly younger (5.0 vs 5.4 months, p=0.03) and smaller (6.1 vs 6.5 kg, p=0.003) but had similar rates of post-operative complications and similar hospital length of stay.

Conclusions:
In a large cohort of infants with SVD surviving to hospital discharge after S1P, PD had minor associations with pre-operative risk factors and no significant association with subsequent outcomes through time of BDG.
Abstract 16783: Beta-Blockers and ACE Inhibitors Improve Long-Term Survival In Renal Transplant Recipients: Results From 10 Year Follow-Up in 321 Patients
Authors: Aftab Waqas , Rasool Shuja , Varadarajan Padmini , Pai Ramdas G
Published: April 2024

Background:
End stage renal disease is associated with a dismal cardiovascular prognosis and is improved to some extent by renal transplantation. Hence, we analyzed the cardiovascular predictors of survival after renal transplantation to gain insights into potential therapeutic targets to improve their outcomes.

Methods:
We abstracted the medical records of 321 consecutive patients from our institution who had received renal transplantation between 1995 and 2003. Survival was analyzed as a function of clinical and pharmacological variables.

Results:
The characteristics of the 321 patients were as follows: age at transplant 49+13 years, 40% males, HTN in 89%, diabetes mellitus (DM) in 37% and LV EF 58+17%. Over a follow up of 10+4 years, there were 119 deaths. Cox proportional hazard model showed DM (HR 1.5, P= 0.05), prior myocardial infarction (MI) (HR 2.6, P=0.001), perioperative MI (HR 2.6, P=0.002), and lack of beta blocker (BB) therapy (HR 1.6, P=0.06) and ACEI (HR 1.9, p=0.006) to be independent predictors of higher mortality. The 10 year survival in patients receiving BB was 80% vs. 63% for no BB and 82% for those receiving ACEI vs. 62% for no ACEI.

Conclusions:
(1) Annualized mortality after renal transplantation is about 3%, being higher in the aged, diabetics and those with prior or perioperative MI. (2) Use of BB and ACEI therapies are associated with a higher survival independent of CAD or DM indicating a potential protective role in this high risk population.
Abstract 16817: Utility of Digital Assessment of Endothelial Function for Cardiovascular Risk Stratification in Patients with Diabetes Mellitus
Authors: Matsuzawa Yasushi , Sugiyama Seigo , Hitoshi Sumida , Sugamura Koichi , Nozaki Toshimitsu , Ohba Keisuke , Konishi Masaaki , Matsubara Junichi , Akiyama Eiichi , Iwashita Satomi , Matsui Kunihiko , Umemura Satoshi , Kimura Kazuo , Ogawa Hisao
Published: April 2024

Background:
Patients with diabetes have an increased risk in developing cardiovascular complications, caused by endothelial dysfunction and accelerated atherosclerosis. However, among patients with diabetes, the degree of atherosclerosis is various. Endothelial dysfunction could provide a significant prognostic value to predict future cardiovascular events. Digital reactive hyperemia-peripheral arterial tonometry (RH-PAT) is a noninvasive and operator-independent method to evaluate endothelial function. We examined whether the assessment of endothelial dysfunction could provide comprehensive cardiovascular risk stratification in patients with diabetes.

Methods:
This study included 160 consecutive stable high-risk patients with diabetes suspected of coronary artery disease (CAD). The RH index (RHI) was measured before cardiac catheterization, and examined the presence of CAD by angiography (>50% stenosis). Coronary plaques were classified angiographically as simple or complex according to Ambrose criteria.

Results:
In diabetic patients, the values of RHI were significantly attenuated in patients with CAD (n = 140) compared to those without CAD (n = 20) (non-CAD: 0.72 ± 0.23, versus CAD: 0.51 ± 0.17, p < 0.01). Furthermore, RHI values of diabetic patients with complex coronary lesion (n = 92) were significantly lower than those with simplex coronary lesion (n = 48) (simple-CAD: 0.56 ± 0.14, versus complex-CAD: 0.48 ± 0.18, p < 0.01). Multivariable logistic regression analysis among various risk factors identified lower RHI values as an independent determinant of coronary plaque complexity in patients with diabetes (the odds ratio was 0.69 [95% confidence interval: 0.56 to 0.85], p < 0.01). By receiver operating characteristics analysis, RHI had a significant prognostic value to predict complex coronary plaques (the area under the curve: 0.73 [95% confidence interval: 0.65 to 0.81], p < 0.001).

Conclusions:
Advanced endothelial dysfunction significantly correlated with the presence of CAD, particularly with the coronary complex plaque in patients with diabetes. Among diabetic patients, the assessment of endothelial function can provide clinically important information to identify vulnerable patients with vulnerable plaque.
Abstract 16818: Circulating Cardiac Troponin I as Detected By a High-Sensitivity Assay among Patients Hospitalized with Acute Decompensated Heart Failure
Authors: Kociol Robb D , McNulty Steven E , Lee Kerry L , Apple Fred S , Tracy Russell P , Hernandez Adrian F , Mentz Robert J , Braunwald Eugene , O'Connor Christopher M , Felker G. Michael
Published: April 2024

Background:
Detectable circulating cardiac troponin (cTn) has been associated with increased risk of death or rehospitalization in patients hospitalized with acute decompensated heart failure (ADHF). Little is known about the association between cTn levels measured using high-sensitivity assays (hsTn) and outcomes.

Methods:
We analyzed hsTnI data from patients enrolled in DOSE - a randomized controlled trial of diuretic strategies in ADHF. hsTnI was measured at baseline at a central academic core laboratory using a high-sensitivity assay (Beckman Coulter hs-cTnI) with a lower limit of detection of 2.06 pg/mL and a 99
th
percentile upper reference limit (URL) of 8.6 pg/mL. We used the Cox regression model to look for an association between baseline hsTnI (log transformed) and 60-day clinical outcomes (death, rehospitalization, or emergency department [ED] visit).

Results:
Among 308 patients in the trial, 290 had baseline cTnI values available for analysis. All patients had detectable hsTnI levels at baseline, and 92% had hsTnI levels above the 99
th
percentile URL. The median (IQR) hsTnI was 21.8 pg/mL (13.1, 42.9). Median hsTnI stratified by gender, left ventricular ejection fraction, HF etiology and serum creatinine (Cr) are reported in the
Table.
Women and those with Cr > 1.5 had higher median hsTnI values. The observed event rate was 46.2% within 60 days. We found no association between hsTnI and days free of death, rehospitalization, or ED visit after univariate analysis (P=0.11), or after adjustment for covariates (P=0.35).

Conclusion:
Using a high sensitivity hsTnI assay, 100% of ADHF had detectable circulating hsTnI and over 92% of patients had a hsTnI level above the 99
th
percentile URL. These data suggest that such a cut point may have little relevance in the ADHF population when using high sensitivity assays. We found no association between hsTnI levels and clinical outcomes at 60 days.
Abstract 16844: Uncoupling of Myocardial Response to Hypoxia in Nonischemic Heart Failure is Associated with Intraventricular Conduction Disease and Reduced Response to Beta-Blockers
Authors: Kao David P , Tipney Hannah , Gilbert Edward M , Hunter Lawrence E , Lowes Brian D , Bristow Michael R
Published: April 2024

Background
In heart failure patients treated with b-blockers the ability to predict likelihood of improvement in LVEF using clinical features is limited. Molecular profiling may improve individualization of HF prognosis.

Hypothesis
Knowledge-based analysis of myocardial gene expression identifies pathways relevant to prediction of LVEF improvement in response to beta-blockers.

Methods
51 patients with nonischemic dilated cardiomyopathy underwent myocardial biopsy before starting a beta-blocker, and mRNA expression was quantified. Genes associated with LVEF response over 12 months (improvement ≥ 5% and final LVEF ≥35%) were identified (p ≤ 0.001). Top genes were combined with biomedical knowledge in public databases and literature. Combined data were explored to identify pathways of interest. One biologic pathway was selected, and expression of related genes was analyzed. Patients were grouped based on similarities in pathway gene expression, and clinical features were integrated to identify associated phenotypes.

Results
Three genes associated with response to hypoxia were predictive of LVEF response (HIF-1AN, HK2, BHLHE40). HIF-1α, VEGF, and p53 were identified as up- and down-stream members of this pathway also known to play a role in HF. Analysis of relative expression of HIF-1α, BHLHE40, VEGF, and p53 divided patients into 4 groups (Figure 1). One group was associated with a significantly lower rate of LVEF response (OR 0.16, p=0.01) and a higher likelihood of QRS interval > 120 msec (OR 34.1, p<0.0001). This group had the highest levels HIF-1a expression and lower expression of BHLHE40, VEGF, and p53 relative to HIF-1α compared with other groups.

Conclusions
Uncoupling of molecular signaling in myocardial response to hypoxia is associated with widened QRS interval and reduced likelihood of LVEF improvement with beta-blocker therapy. This is a group of patients in whom initial treatment with CRT may be indicated.
Abstract 16855: Comparison of Non-ST Segment Myocardial Infarction One-Year Outcomes at Academic vs Non-Academic Hospitals
Authors: Subherwal Sumeet , Roe Matthew T , Holmes Dajuanicia , Thomas Laine , Alexander Karen P , Wang Tracy Y , Peterson Eric D
Published: April 2024

Background:
Prior studies have found academic hospitals provide more consistent evidence-based therapies and do more intervention in non-ST segment myocardial infarction (NSTEMI) patients than at nonacademic centers; whether these difference in care process translate into differences in short- or long-term outcome is unclear.

Methods:
We compared 12,381 NSTEMI patients age >65 years treated at 107 academic hospitals with 30,954 NSTEMI patients treated at 341 non-academic hospitals from Feb 2003-Dec 2006 in CRUSADE Registry. Clinical data were then linked to Medicare longitudinal claims data. Short-term (30 days) and 1-year mortality among academic vs not centers was compared were after adjusting for clinical characteristics using a validated risk model (C-index 0.75).

Results:
Patients treated at academic centers had slightly more cardiac risk factors. Academic centers used more early invasive strategy (49% vs 43%), in-hospital PCI (36% vs 30%), and CABG (10% vs 8%) than nonacademic centers, and were more likely to use evidence based discharge therapies (ASA 95% vs 93%; beta blocker 93% vs 91%; statin 81% v 74%; ACI or ARB 69% vs 67%). The 30-day mortality was 9.8% overall (8.9% academic vs 10.2% nonacademic); 1-year mortality was 24.6% (23.3% academic vs 25.1% nonacademic.). Academic centers had superior 30-day and 1-year risk adjusted outcomes than nonacademic centers (Table).

Conclusion:
Patients with NSTEMI treated at academic centers received more aggressive evidence based treatments and interventions that were associated with improved short and long-term outcomes.
Abstract 16872: Levosimendan Modulates Brain Injury Pattern in a Model of Infant Cardiopulmonary Bypass
Authors: Namachivayam Poongundran , Smolich Joe , Shields Amy , Konstantinov Igor E , Rees Sandra , Shekerdemian Lara
Published: April 2024

Introduction.
Brain immaturity and cardiopulmonary bypass (CPB) are important factors in the pathophysiology of brain injury in infants undergoing cardiac surgery. However, the impact of Levosimendan (Levo), a novel inodilator, on circulatory hemodynamics and microscopic markers of brain injury have not been fully investigated. We therefore studied the effects of Levo on global and regional hemodynamics and brain immunohistochemistry in a lamb model of infant CPB.

Methods.
Eighteen 1-week-old and eighteen 4-week lambs were anesthetized and instrumented with vascular catheters and aortic and right carotid artery transit-time flow probes. At each age, similar numbers were allocated to one of three treatment groups: 1) Non-CPB control, 2) CPB and 3) CPB+Levo. CPB animals underwent aortic and right atrial cannulation, and all received 120 min of CPB, with 90 min of aortic cross-clamp (XC) and cardioplegic arrest. Lambs in Group 2 received dopamine, and in Group 3, dopamine plus Levo, on weaning from CPB. Hemodynamic measurements were recorded pre-CPB and at 60, 120, 180 and 240 min after XC removal. At the end of the study, brains were fixed by perfusion and prepared for immunohistochemical analysis. Data were analysed with analysis of variance and P<0.05 considered significant.

Results.
After CPB in 1-week lambs, cardiac output fell by 25% (P<0.05) and carotid artery flow by 45% (P<0.05), while in the CPB+Levo group, cardiac output was preserved and carotid artery flow fell by 23% (P<0.05). After CPB in 4-week lambs, cardiac output decreased by 26% (P<0.05) and carotid artery flow by 32% (P<0.05), but in the CPB+Levo group, both cardiac output and carotid artery flow were preserved. On brain immunohistochemistry, an increased density of microglia (P<0.05) was evident in deep white matter of the CPB+Levo group in 4-week, but not 1-week lambs.

Conclusion.
In a model of infant CPB, Levo prevented an early post-operative fall in cardiac output after CPB. However, while Levo preserved post-CPB carotid artery blood flow in 4-week lambs, this was associated with microscopic changes suggestive of increased brain injury. The impact of Levo on cerebral hemodynamics and evolution of brain injury in the immature circulation after CPB warrants further investigation.
Abstract 16895: Micrornas Control Endothelial Progenitor Senescence via Regulating Plk2 Expression
Authors: Zhu Shoukang , Deng Shanming , Ma Qi , Zhang Taifang , Zhuo Degen , Wang Liyong , Goldschmidt Pascal J , Dong Chunming
Published: April 2024

Background:
With advancing age the regenerative properties of somatic stem cells deteriorate in part due to cellular senescence, eventually leading to the diminished repair capability. Endothelial progenitor cells (EPCs) play an important role in angiogenesis. Several miRNAs have been reported to be critical modulators for EPC plasticity. The
aim
of this study was to determine whether miRNAs regulated age-related senescence in lineage negative bone marrow cells (lin
-
BMCs) enriched for EPCs.

Methods:
Lin
-
BMCs were isolated from young (3-week-old) wild type (WT) and apoE
-/-
C57BL/6 mice and aged WT (29-month-old) and apoE
-/-
(12 month-old) mice. Global miRNA and gene expression profiling were analyzed.

Results:
Using genome-wide miRNA analysis, we found that miR-146a was increased 6.3-fold and 3.4-fold in aged WT and apoE
-/-
lin
-
BM cells, respectively, relative to their young counterparts. Microarray analysis showed that the Polo-like kinase 2 (Plk2), a member of the ‘polo’ family of serine/threonine protein kinases that are critical regulators of cell cycle progression or apoptosis, was decreased 18-fold in aged lin
-
BMC as compared to young cells. Luciferase assay showed miR-146a substantially inhibited WT Plk2-3’-UTR-luciferase activity in 293T cells, but not mutant Plk2-3’-UTR-luciferase reporter. Overexpression of lentiviral-derived miR-146a resulted in reduction of Plk2 expression, increased senescence-associated (SA) β-gal expression and decreased vascular tube formation in young EPCs, whereas miR-146a antagomir rejuvenated aged EPCs, causing increased Plk2 expression, decreased SA β-gal expression and enhanced vascular tube formation. Furthermore, knockdown of Plk2 by its siRNA resulted in increased senescence and diminished vascular tube formation.

Conclusions:
Using genomic and functional studies, we have discovered miR-146a controls age-associated EPC senescence via regulating Plk2 expression, thus negatively affecting their vascular repair capacity, which may impact atherogenesis. These findings advance our understanding of EPC aging and provide molecular targets for genetic modification to increase the therapeutic efficacy of EPCs in preventing and repairing vascular damage in atherosclerosis.