bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 10340: Multi-Center Experience With Endovascular Treatment of Aortic Coarctation and Post-Surgical Complications of Coarctation Repair in Adults
Authors: Erben Young , Oderich Gustavo S , Verhagen Hence J , Witsenburg Maarten , Van den Hoven Allard T , Debus Eike S , Kolbel Tilo , Arko Frank R , Torsello Giovanni B , Torsello Giovanni F , Lawrence Peter F , Harlander-Locke Michael P , Bacharach J. Michael , Jordan William D , Eskandari Mark K
Published: April 2024

Objective:
To evaluate outcomes of endovascular treatment of aortic coarctation in the adult, either newly diagnosed or due to recurrent coarctation and pseudoaneurysm formation

Methods:
Clinical data and imaging studies of 93 patients treated at nine institutions from 1999-2015 were reviewed. Primary end-points were morbidity and mortality. Secondary end-points were stent patency and need for re-intervention

Results:
There were 54 male and 39 female patients with a mean age of 44±17 years, including 32 with de novo coarctation (mean 48±16 years) and 61 with prior open repair during childhood, who required endovascular re-intervention (mean: 30±17 years after initial repair). Indications for treatment were: resistant hypertension (32%), left ventricular hypertrophy (23%) and claudication (20%). Imaging studies included: computed tomography angiography (CTA) (42%), CTA and magnetic resonance angiography (MRA) (37%), MRA (13%), angiography (5%) and ultrasound (2%). Endovascular treatment was performed using stent grafts (55%), balloon expandable bare metal in (28%) or covered stents (15%) and primary angioplasty alone (1%). Mean lesion length and diameter were 64±50mm and 20±7mm, respectively. Mean systolic pressure gradient decreased from 24±18mmHg to 5±8mmHg after treatment, (p<0.001). Four patients had intraprocedural complications including: rupture in two, type 1A endoleak and access hemorrhage in one each. Perioperative complications occurred in six: aortic dissection in three, thrombus migration into renal artery, spinal headache requiring blood patch and lung hemorrhage in one patient each. Two patients died within 30-days from hemorrhage and cardiopulmonary arrest. After a mean follow up time of 7±21 years, nearly all patients (98%) had symptom improvement and all stents were patent. Re-intervention was needed in 11%. 2 patients died from coarctation related causes including rupture of an infected graft and visceral ischemia

Conclusions:
In this multi-center study, endovascular repair was a safe and effective treatment for de novo coarctation and post-surgical complications of coarctation repair in adults. Rate of procedural complications and re-interventions were low with high procedural and long-term clinical success
Abstract 10450: Prognostic Effect of Estimated Glomerular Filtration Rate in Patients With Cardiac Arrest Undergoing Extracorporeal Cardiopulmonary Resuscitation
Authors: Kuroki Norihiro , Abe Daisuke , Iwama Tooru , Tateishi Kazuya , Kaneko Masakazu , Harunari Tomohiko , Yui Yoshiaki , Yuba Takao , Sugiyama Kazuhiro , Akashi Akiko , Hamabe Yuichi , Sato Akira
Published: April 2024

Introduction:
Extracorporeal membrane oxygenation (ECMO) can provide immediate and adequate systemic circulation and oxygenation in patients with refractory cardiac arrest. Even mild renal dysfunction has been identified as an independent cardiovascular risk factor. We hypothesized that renal dysfunction influences resuscitation outcomes. The aim of this study was to elucidate the association between initial renal function just before implantation and clinical outcome in patients undergoing extracorporeal cardiopulmonary resuscitation (ECPR).

Methods:
A cohort of 298 patients who underwent ECMO at our hospital was registered from January 2005 to April 2015. After excluding 70 patients with non-cardiac arrest, we analyzed the clinical outcome which was defined as all-cause death at 30 days of the remaining 228 patients (58.4±14.8 years old, 81% male, 196 with cardiogenic events, 32 with non-cardiogenic events).

The patients were divided into 2 groups according to initial estimated-glomerular filtration rate (eGFR). Non-CKD Group: eGFR ≥60ml/min/1.73m2 (n=70); CKD Group: eGFR <60 (n=158).

Results:
The rate of out-of-hospital cardiac arrest was 40%. In baseline characteristics, Non-CKD group was significantly younger (52.7 vs. 61.3 years old), lower incidence of hypertension (28 vs.52 %) and known coronary artery disease (6 vs 21%) in past history and lower BUN (14.5 vs. 26.2 mg/dl, all p<0.05) than CKD group.

Incidence of all-cause death at 30 days was significantly lower in the non-CKD than CKD group (53 vs. 78%, p<0.0001). CKD was an independent predictor of mortality after adjustment for multiple cofounders (OR: 4.49, 95% CI: 2.07-9.77, p<0.001). Kaplan-Meier curve showed better outcome in the non-CKD versus CKD group (p<0.01).

Conclusions:
Initial low e-GFR just before implantation provides worse clinical outcome in patients undergoing ECPR.
Abstract 10772: Could Tolvaptan Protect Renal Function in the Early Postoperative Period After Cardiac Surgery?
Authors: Kishimoto Yuichiro , Nakamura Yoshinobu , Harada Shingo , Ohnohara Takeshi , Horie Hiromu , Kurashiki Tomohiro , Kishimoto Satoru , Shiraya Suguru , Saiki Munehiro , Nishimura Motonobu
Published: April 2024

Introduction:
Tolvaptan (TV), a vasopressin V2 inhibitor, has a strong diuretic effect, which is beneficial for body fluid management in patients with acute heart failure (AHF). Several studies have reported that TV significantly reduces worsening renal function (WRF), which has recently been highlighted as an exacerbation factor in the treatment of AHF. We hypothesized that concomitant administration of TV with conventional diuretic treatment is beneficial for perioperative body fluid management in patients who have undergone cardiac surgery. In this study, we prospectively randomized the patients into the TV group, in which TV was administered in addition to conventional diuretics, and the control group, in which the patients received conventional diuretics only.

Methods:
A total of 176 patients who underwent cardiac surgery were divided into 2 groups, which were the TV group (TV + furosemide, 90 patients) and conventional diuretic treatment group (Control [C], furosemide with or without spironolactone, 86 patients). We compared urine output for 3 days after surgery, the time required to restore the preoperative body weight, and the incidence of WRF between the 2 groups. In the TV group, patients received TV 7.5mg/day orally starting on POD1 and continued to take TV up to POD 5. WRF was defined as a rise in the serum creatinine level (Cr) of ≥0.3 mg/dL.

Results:
The mean daily urine output from POD1 to POD 3 of the TV group (2672 ± 769 mL/day) was higher than that of the C group (2240 ± 529 mL/day) (p = 0.001). The time required to restore preoperative body weight was shorter in the TV group (3.8 ± 1.4 days) than in the C group (4.8 ± 2.0 days) (p=0.003). While the highest postoperative Cr of the TV group (1.01 ± 0.50 mg/dL) was the same as that of the C group (1.16 ± 0.91 mg/dL) (p=0.25), the incidence of WRF in the TV group (9 patients, 10%) was significantly lower than in the C group (24 patients, 28%) (p=0.007), which might indicate the protective effect of TV against WRF in the patients undergoing cardiac surgery.

Conclusions:
Administration of TV with conventional diuretics in the early postoperative period after cardiac surgery could be beneficial in maintaining urine output without affecting renal function, which may help to avoid WRF after cardiac surgery.
Abstract 10883: C-GRApH: A Validated Scoring System for the Early Risk Stratification of Neurologic Outcomes After Out-of-hospital Cardiac Arrest Treated With Therapeutic Hypothermia
Authors: Kiehl Erich L , Parker Alex M , Matar Ralph M , Gottbrecht Matthew , Johansen Michelle C , Adams Mark P , Griffiths Lori A , Bidwell Katherine L , Menon Venugopal , Enfield Kyle B , Gimple Lawrence W
Published: April 2024

Background:
Out of hospital cardiac arrest (OHCA) has 90% mortality, primarily from neurologic injury. Due to a lack of accurate early risk stratification models, guidelines advocate delayed prognostication of neurologic outcomes (NO) ≥72 hours post OHCA in patients treated with therapeutic hypothermia (TH). Here, we derive and validate a scoring system that uses objective data available at hospital presentation to risk stratify NO early post OHCA in the TH era.

Methods:
Demographics, pre OHCA diagnoses, arrest characteristics, and initial lab studies were compared between favorable and poor NO at hospital discharge, defined as cerebral performance category (CPC) 1-2 and 3-5 respectively, in a derivation cohort of 122 consecutive adult patients treated with TH (32-34
o
C) post OHCA at a tertiary care US hospital from 2008-12. Inputs meeting
a priori
cutoffs ρ<0.1 in univariate and ρ<0.05 in subsequent stepwise multivariable analyses were dichotomized to create a scoring system (C-GRApH) with equal weighting. C-GRApH was validated internally from 2013-4 (n=72) and externally at a larger health system (quaternary care and satellite hospitals) from 2012-4 (n=272).

Results:
In the derivation and validation cohorts, 34 and 32% of patients survived to discharge, 27 and 21% with favorable NO respectively. The C-GRApH score (range 0-5) includes the following variables: pre-OHCA CAD (C); initial glucose >200 (G); non VT/VF rhythm of arrest (R); age >45 (A); and initial pH ≤7.0 (pH). The c-statistic was 0.82 for predicting poor NO in both cohorts with similar risk stratification observed. Favorable NO at hospital discharge was 70% in low (≤1, n=60), 20% in medium (2-3, n=307), and 2% in high (≥4, n=97) scores in the composite cohort.

Conclusions:
The C-GRApH score effectively stratifies NO in OHCA treated with TH early post-arrest using data readily available at initial presentation and identifies a subset of patients (scores≥4) where TH and intensive care are of limited benefit.
Abstract 10918: AST-120 Prevents the Progression of Kidney Injury After Myocardial Infarction
Authors: Fujii Hideki , Kono Keiji , Yonekura Yuriko , Nakai Kentaro , Goto Shunsuke , Yamashita Yusuke , Sugano Mikio , Goto Sumie , Fujieda Ayako , Ito Yoshiharu , Nishi Shinichi
Published: April 2024

Introduction:
Chronic kidney disease (CKD) is a crucial risk factor for cardiovascular disease (CVD), and combined CKD and CVD further increases morbidity and mortality. Therefore, the prevention of kidney injury is essential for the improvement of prognosis of patients with CVD. Among the many factors, increased oxidative stress plays a role for the pathogenesis of CKD and CVD.

Hypothesis:
AST-120, which is an oral charcoal adsorbent, may prevent kidney injury by reducing one of the uremic toxins, indoxyl sulfate (IS) and oxidative stress in a rat myocardial infarction (MI) model.

Methods:
At 10 weeks of age, male spontaneously hypertensive rats (SHR) were divided into 3 groups: SHR (n=6), MI (n=8) and MI+AST-120 groups (n=8) and the administration of AST-120 was started at 11 weeks of age. MI was induced by the ligation of the left coronary artery in the MI and MI+AST-120 groups at 10 weeks of age. At 18 weeks of age, rats were sacrificed, and blood and urine analyses, mRNA expression analysis, renal histological analysis, and echocardiography were performed in these groups.

Results:
At 18 weeks of age, though there were no significant differences in blood pressure and kidney function, serum IS levels and urinary IS excretion were reduced in the AST-120 groups compared to the MI groups. Urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion, serum tissue growth factor beta (TGF-β) levels, serum neutrophil gelatinase-associated lipocalin (NGAL) levels, serum kidney injury molecular-1 (KIM-1) levels and serum,L-type fatty acid binding protein (L-FABP) levels were also decreased in the MI+AST-120 group compared to the other two groups. The mRNA expressions of NADPH oxidase and NF-kappa B, connective tissue growth factor (CTGF) in the kidney were significantly decreased in the MI+AST-120 group compared to the MI group. In vitro data using LCC-PK1 cells also supported the influence of IS on kidney injury. Further immunohistological analysis revealed that intrarenal oxidative stress was reduced by AST-120 administration.

Conclusions:
Our data showed that IS increased after MI and AST-120 is suggested to have protective effects on kidney injury after MI through the suppression of oxidative stress.
Abstract 10938: Outcomes of Coronary Artery Bypass Grafting in 1.9 Million Medicare Patients From 1999-2010
Authors: Schaffer Justin M , Lingala Bharathi , Fann James I , Burdon Thomas A , Ogden W D , Woo Y J , Boyd Jack H
Published: April 2024

Introduction:
Coronary artery bypass grafting (CABG) remains a mainstay of treatment in patients with coronary artery disease. Outcomes of CABG from a large modern U.S. cohort (the Medicare database) were analyzed, with a focus on outcomes.

Methods:
Medicare patients undergoing CABG from 1999-2010 were assessed. ICD-9 and CPT codes were used to describe operative details. Survival distributions were estimated with the Kaplan-Meier method, and compared with an age-/sex-/race-matched general US population cohort. A Cox proportional hazards analysis determined variables associated with survival. Cubic-spline analyses were used to assess hospital and surgeon volume-outcome relationships.

Results:
Median survival following CABG for the entire cohort (n=1,902,315) was 9.43 years (95% confidence intervals [CI] 9.41-9.45) (Figure 1A), and was 10.02 years (95% CI: 10.00-10.04) in isolated CABG (n=1,523,529) recipients (Figure 1B). During the 12 year study period, Medicare patients underwent CABG at 1,391 U.S. hospitals and by 5,899 U.S. surgeons. Multivariable analysis identified multiple predictors of death including age, gender, race, patient comorbidities, prior cardiac surgery, year of operation, adjunct cardiac procedures (e.g. valve repair/replacement or aortic repair), the lack of internal mammary artery (IMA) use, the absence of billing for cardiopulmonary bypass, and both hospital and surgeon volume. A transition point was identified in the surgeon-volume and hospital-volume relationships suggesting a volume beyond which additional case numbers only improved outcomes minimally (Figures 1C/1D).

Conclusions:
Survival following CABG in Medicare patients is robust. Even in this elderly cohort, the use of a single IMA was associated with significantly improved outcomes, and bilateral IMA use was associated with an even lower hazard for death compared with single IMA. Both hospital and surgeon volume had strong associations with survival.
Abstract 11040: Poloxamer 188 Protects Endothelial Cells From Hypoxia/Reoxygenation Injury - Implications for Cardio- and Neuroprotection After Cardiac Arrest
Authors: Salzman Michele M , Afzal Aqeela , Cheng Qunli , Bates Frank S , Riess Matthias L
Published: April 2024

Introduction:
Cardiac arrest is a leading cause of death. Even with the best CPR, many patients die or suffer severe cardio-cerebral damage. Reintroduction of blood flow at the start of CPR after systemic ischemia may cause additional injury to organs such as the heart and brain beyond that caused by the ischemia itself. Determining the mechanism of action of a compound administered during CPR on the cellular dysfunction caused by ischemia/reperfusion could improve CPR practices in the future.

Hypothesis:
Poloxamer 188 (P188), with its unique hydro-/lipophilic chemical properties, protects coronary and cerebral endothelial cells against hypoxia/reoxygenation (H/R) injury.

Methods:
Endothelial cells (human coronary artery [HCAECs] and rat brain [RBECs]) underwent 2 hrs hypoxia (1% O2) then 2 hrs reoxygenation ± P188. Endpoints were markers of cellular injury (lactate dehydrogenase [LDH] release, mitochondrial dehydrogenase activity), proliferation, and nitric oxide (NO) release. Statistics: Student t-test followed by SNK post hoc comparisons, *p<0.05 vs control, † vs normoxia.

Results:
In HCAECs, H/R caused significant LDH release compared to cells in normoxic conditions (†0.774±0.084 vs 0.562±0.141 abs/mg protein; n=5). P188 significantly decreased LDH release in both hypoxic and normoxic conditions (*0.215±0.024 vs *0.273±0.02). P188 also significantly attenuated decreased mitochondrial dehydrogenase activity caused by H/R (*0.379±0.015 vs 0.468±0.035 abs/mg protein). NO measurement by DAF-2DA fluorescence showed higher levels in cells treated with P188 upon reoxygenation than controls (*164,944±6,716 vs 139,942±2,511 RFUs). In proliferation assays of HCAECs and RBECs, there was significantly lower proliferation following H/R than during normoxia (HCAECs: 16,030±716 vs †7,500±465; RBECs: 13,563±1,251 vs †7,323±297 cells/well). This decrease was dose-dependently attenuated by P188 when compared to control (HCAECs: 1μM, *8,523±495; 1mM, *8,827±375. RBECs: 1μM, *7,782±274; 1mM, *8,930±177).

Conclusions:
HCAECs and RBECs were protected by P188 against H/R, and P188 also increased NO release in HCAECs. P188 protection of cardiomyocytes and neurons may be mediated by the preservation of NO release from the endothelium.
Abstract 11340: The Plasma Membrane Calcium ATPase 4 Signaling in Cardiac Fibroblasts Mediates Cardiomyocyte Hypertrophy
(Best of Basic Science Abstract)
Authors: Mohamed Tamer M , AbouLeisa Riham , Stafford Nicholas , Zi Min , Prehar Sukhpal , Baudoin Florence , Cartwright Elizabeth , Neyses Ludwig , Oceandy Delvac
Published: April 2024

Plasma membrane calcium ATPase 4 (PMCA4) is a ubiquitously expressed Ca
2+
pump that is important in mediating molecular signaling in the heart. Here we show a novel role of PMCA4 in cardiac fibroblasts in controlling cardiac hypertrophy.

We generated three PMCA4 knockout mouse strains: i) PMCA4 global knockout (PMCA4
-/-
); ii) PMCA4 cardiomyocyte-specific knockout (PMCA4
cko
); iii) PMCA4 fibroblast-specific knockout (PMCA4
fko
). Following transverse aortic constriction (TAC) for 5 weeks, PMCA4
-/-
and PMCA4
fko
mice displayed a significantly reduced hypertrophy compared to control mice. In contrast, the PMCA4 cardiac specific knockout (PMCA4
cko
) mice did not show any protective effect following TAC, prompting us to hypothesise that the protective effect might be due to PMCA4 ablation in fibroblasts. Microarray analysis revealed a ~100 fold upregulation of secreted frizzled-related protein 2 (sFRP2) in PMCA4
-/-
fibroblasts, which was further confirmed by qRT-PCR and Western blot. sFRP2 is a potent inhibitor of the Wnt/β-catenin pathway. We then cultured wild type (WT) cardiomyocytes with conditioned medium from either PMCA4
-/-
or WT fibroblasts. In response to phenylephrine stimulation, cardiomyocytes cultured in PMCA4
-/-
fibroblast–conditioned medium displayed 88% less hypertrophy than those cultured in WT fibroblast–conditioned medium (P<0.01). Mechanistically, PMCA4
-/-
fibroblasts showed a significant elevation in NFκB activity, a transcription factor that regulates sFRP2 expression. Inhibition of NFκB activity significantly reduced the sFRP2 expression in PMCA4
-/-
fibroblasts to a level comparable to WT expression. A chemical library screen identified a novel PMCA4 inhibitor, aurintricarboxylic acid (ATA). ATA treatment enhanced sFRP2 expression in the mouse heart. Importantly, ATA inhibited and reversed TAC-induced cardiac hypertrophy in mice, demonstrating its efficacy in both preventive and therapeutic strategies.

In conclusion, PMCA4-mediated signaling in cardiac fibroblasts plays a key role in controlling cardiac hypertrophy. Cardiac fibroblasts lacking PMCA4 produce higher levels of sFRP2, which protects the neighbouring cardiomyocytes. Finally, PMCA4 is a potential target for cardiac hypertrophy treatment.
Abstract 11462: The Clinical Significance of Pulse Pressure in Patients With Heart Failure With Preserved Ejection Fraction
Authors: Tokitsu Takanori , Yamamoto Eiichiro , Hirata Yoshihiro , Fujisue Koichiro , Sugamura Koichi , Yamamuro Megumi , Kaikita Koichi , Hokimoto Seiji , Sugiyama Seigo , Ogawa Hisao
Published: April 2024

Background:
Although pulse pressure (PP) has been recognized as a risk factor for various cardiovascular diseases, its association with cardiovascular outcomes in patients with heart failure (HF) with preserved ejection fraction (HFpEF) remains uncertain. This study aimed to assess the relationship between PP and cardiovascular outcomes in HFpEF patients.

Methods:
We enrolled 317 consecutive HFpEF patients, admitted to Kumamoto University Hospital from 2007 to 2013. We measured blood pressure (BP) by using ankle brachial index (ABI) form on admission. PP values higher than 65 mmHg were defined as high-PP as reported previously.

Results:
PP had a significant positive correlation with pulse wave velocity (PWV) (r=0.50, p<0.001), and negative correlations with estimated glomerular filtration rate (eGFR) (r=0.32, p<0.001) and hemoglobin levels (r=0.27, p<0.01) in HFpEF patients. In multivariate logistic-regression analysis, age, hemoglobin, eGFR and the presence of diabetes mellitus were independently associated with high-PP. PP also had strong and significant correlations with eGFR, PWV and hemoglobin level. In multivariate-Cox-proportional hazard analysis, high-PP (p=0.01), the presence of ischemic heart disease (p=0.01), and B-type natriuretic peptide (BNP) values (p=0.01) were independently associated with the occurrence of cardiovascular events (CVE). In Kaplan-Meier analysis, HFpEF patients with high-PP had a significant higher risk of CVE and HF-related events (both, log-lank test, p<0.01). Multivariate-Cox-hazard analysis identified that high-PP, but not high-systolic BP (SBP), as an independent predictor of both CVE (hazard ratio [HR]: 2.15, p=0.01) and HF-related events (HR: 4.37, p<0.01).We further stratified patients into four groups combined with PP and BNP values, HFpEF patients with both high-PP and high-BNP(cutoff:100pg/dL) had the highest risk of HF-related events and CVE (both, log-rank test, p<0.001), indicating their usefulness in risk prediction in HFpEF patients.

Conclusion:
High-PP, rather than high-SBP, was closely associated with the prognosis of patients with HFpEF. PP is the useful marker for risk stratification in HFpEF.
Abstract 11483: Possible Criteria to Prospectively Define and Characterize Myocardial Denervation in Ischemic Patients With Ventricular Tachycardia (VT) Using I123-Meta-iodobenzylguanidine-defined (I123-MIBG)
Authors: Abdulghani Mohammed , Duell John , Smith Mark , Chen Wengen , Ume Kiddy L , Bob-Manuel Tamunoinemi , See Vincent , Imanli Hasan , Saliaris Anastasios , Shorofsky Stephen , Dilsizian Vasken , Dickfeld Timm
Published: April 2024

Introduction:
Cardiac innervation is a critical component in ventricular arrhythmogenesis. However, a clear definition and electrophysiological characterization of denervation zone (DZ), transitional innervation zone (TZ) and normal innervation zone (NZ) does not exist, which allow a standardized use for clinical trials and image-guided treatment/ablation.

Method:
15 patients with ischemic VT undergoing VT ablation underwent pre-procedural sympathetic innervation imaging using I123-MIBG SPECT. Sequential short axis I123-MIBG images were visually classified by 2 experienced cardiac nuclear radiologists into zones of DZ, TZ, and NZ. ROC curves were used to identify the best cut-offs of normalized voxel-based signal intensities. After reconstruction and integration of 3D innervation maps with high-density electrophysiological maps, voltage and signal characteristics were determined.

Result:
All patients demonstrated areas of denervation, TZ and normal innervation. Innervation defects were localized in the inferior (100%), lateral (73%), septal (60%), apical (20%) and anterior wall (6%). Normalized MIBG uptake in areas of denervation was 25% (Q1-Q3 15.3-31.7%) [min-max 4-50%], increased to 40% (Q1-Q3 30.2-43.6%) [14-72%] in the TZ (p=0.05) and was highest in normal myocardium (NZ): 67% (Q1-Q3 52.2-71.4%) [39-100%] (p<0.001). ROC curve- defined best cut-offs for DZ, TZ and NZ were <31%, 31-47 and >47%. Local electrograms in denervated myocardium (n=1487) were abnormal (83%), fractionated (10%), normal (4%) and with diastolic potentials (3%). In the TZ (n=611) signals were abnormal (82%), fractioned (14%), normal (3%) and with diastolic potentials (1%). Bipolar voltages of 1.5mV were equally commonly in denervated (35%, 36%, and 29%, p>0.05) and transition zone (35%, 35%, and 30%, p>0.05).

Conclusion:
Denervated, transitional and normally innervated myocardium was best defined by <31, 31-47% and >47% tracer uptake, which provides for the first time quantitative cut-offs for future diagnostic and therapeutic trials. As voltage/signal characteristics were unable to predict innervation categories, cardiac imaging remains the critical modality to assess myocardial innervation characteristics.
Abstract 11661: Readmissions Following Congenital Heart Surgery in Infants and Children
Authors: Benavidez Oscar , He Wei
Published: April 2024

Introduction:
Thirty-day readmission among infants and children after congenital heart surgery (CHS) has been under studied despite the complexity and vulnerability of these patients.

Hypothesis:
Readmissions after pediatric CHS are common. There exist risk factors for unplanned readmission.

Methods:
We obtained State Inpatient Databases for Washington, New York, Florida, and California 2009-2011 and selected admissions < 19 years with ICD-9 CM codes indicating CHS. We defined readmission as non-elective hospitalization for a given patient < 31 days of discharge from the index CHS admission. We examined patient demographic and clinical variables and defined complications using the Society of Thoracic Surgeons Congenital Heart complication short list. Case mix was adjusted by using Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) categories. We defined High Resource Use (HRU) admissions as those > 90
th
percentile for total hospital charges. Multivariate analyses using generalized estimating equations estimated to adjusted odds for readmission.

Results:
Among 8,585 index admissions we identified 967 readmissions (11.3%). Median length of stay for readmissions was 5 days, median total charge of $31,973 and mortality rate 1.8%. Among readmissions 16 (1.6%) were for another CHS of which 44% were HRU, complication rate 88% and mortality 6.25%. Common indications for readmission were Pulmonary (pleural effusion, respiratory distress, pneumonia/bronchiolitis), Cardiac (heart failure, pericardial effusion), Infectious (fever, UTI), and GI (dehydration, feeding difficulty, GERD). On multivariable analysis age 1 month - 1 year (adjusted odds ratio [AOR] 1.3 p=0.01); Hispanic AOR 1.2 p=0.03; government-insurance AOR 1.3 p=0.01; RACHS-1 3 complexity AOR 2.4 p<0.001; RACHS-1 4+ complexity 2.0 p=0.001; HRU AOR 1.4 p=0.02; complications AOR 1.1 p=0.04; and emergent index admission AOR 2.0 p<0.001 were risk factors for readmission.

Conclusions:
Over 11% of pediatric CHS admissions result in unplanned readmission. CHS during readmission had higher resource use, complications and death rates. Hispanic race, government insurance, HRU, higher case complexity, complications and emergent index admission are risk factors for readmission.
Abstract 11721: Feasibility of Using a Leadless Patch Heart Rhythm Monitor to Measure Atrial Fibrillation Burden in Community-Based Epidemiological Studies: The Multiethnic Study of Atherosclerosis (MESA)
Authors: Chen Lin Y , Roetker Nicholas S , Folsom Aaron R , Alonso Alvaro , Heckbert Susan R
Published: April 2024

Background:
Whether or not higher atrial fibrillation (AF) burden (% time a person is in AF) is associated with higher risk of adverse outcomes such as stroke remains controversial. Research on AF burden in community-based studies has been hampered by lead-based heart rhythm monitors that only record continuously for short durations and have poor patient compliance.

Hypothesis:
We hypothesized that it is feasible to use a novel leadless patch monitor (Zio
®
Patch [iRhythm Technologies, Inc, San Francisco, CA] that can record continuously for 2 weeks) to investigate AF burden in a sample of MESA participants.

Methods:
Between November 2013 and January 2014, we included 45 (mean age, 71.6 ± 6.2 years; 58% men) participants at the Minnesota field center without prior diagnoses or symptoms suggestive of AF or other arrhythmias; 30 and 15 were randomized to self-application (Group 1) and application by MESA staff (Group 2), respectively. Monitors were mailed to Group 1 and were applied at the field centers by MESA staff for Group 2 participants. We compared the wear time and analyzable time between the 2 groups.

Results:
The mean and median wear and analyzable times were not significantly different between the 2 groups (Table). Only 1 participant in Group 1 wore the monitor for <2 days. Two (4%) participants were diagnosed by the monitor with AF (1 with burden of 0.02% and 1 with burden of 1.34%) and 1 with frequent non-sustained ventricular tachycardia; all participants were referred to their physicians for appropriate treatment and none suffered serious consequences.

Conclusions:
A leadless continuous recording patch monitor can be used effectively to investigate AF burden in asymptomatic subjects in community-based studies. Self-application of the monitor is equivalent to application by research staff which further facilitates the use of this monitor in community-based studies.
Abstract 11738: A Genome-wide Association Analysis Identifies PDE1ADNAJC10 Locus on Chromosome 2 Associated With Idiopathic Pulmonary Arterial Hypertension in the Japanese Population
Authors: Kimura Mai , Tamura Yuichi , Takei Makoto , Kosaki Kenjiro , Tanabe Nobuhiro , Tatsumi Koichiro , Saji Tsutomu , Saji Tsutomu , Satoh Toru , Kamitsuji Shigeo , Kamatani Naoyuki , Sano Motoaki , Fukuda Keiichi
Published: April 2024

Background:
Idiopathic pulmonary arterial hypertension (IPAH) is a rare but fatal disease with a mean survival period estimated to be around 3 years if not treated. Although many familial cases of IPAH exhibit an autosomal dominant mode of inheritance with the majority having mutations in BMPR2, the penetrance is low with an estimated lifetime risk of 20 %. To explain the low penetrance of IPAH associated with BMPR2 mutations, it was hypothesized that other genetic loci as well as environmental factors play roles.

Purpose:
To identify genetic factors associated with IPAH with/ without BMPR2 mutation, we conducted a genome-wide association study (GWAS) followed by a validation study.

Methods and Results:
We performed GWAS in the Japanese population comprising a total of 44 individuals with IPAH and 2,993 controls. The IPAH cases were identified at three major pulmonary hypertension centers in Japan. The controls consisted of 2,002 and 991 healthy Japanese individuals, which were collected at two different times by Japan PGx Data Science Consortium (JPDSC). At first, we conducted discovery GWAS to identify SNPs related to the disease, comparing 23 cases with IPAH (first set) and 2,002 controls at 1,347,690 SNPs, and identified 8 loci each of which had more than one SNP with P values under 10-5. We then attempted to validate the associations observed in the discovery phase using 21 patients (second set) and 991 controls who were independent of the samples used in the discovery GWAS. In the validation study, we examined the associations of 9 SNPs at 8 loci, and only 2 SNPs at one locus showed significant association. And finally, we identified a novel susceptibility locus PDE1A
Abstract 11879: Control of Fibroblast Function by Adrenergic/EPAC System and Potential Role in Atrial Remodeling
Authors: Surinkaew Sirirat , Aflaki Mona , Qi Xiao- Y , Sun Yiguo , Nattel Stanley
Published: April 2024

Introduction:
Heart failure (HF) produces left atrial (LA)-selective fibrosis and atrial fibrillation. HF also causes adrenergic activation, which contributes to remodeling via a variety of pathways mediated by altered signaling molecules, including the exchange protein activated by cAMP (Epac).

Hypothesis:
To evaluate the effects of adrenergic receptor (AR) and Epac1 signaling on LA fibroblast (FB) function and its potential role in HF-induced atrial remodeling.

Methods:
HF was induced in dogs by ventricular tachypacing (VTP, 240 bpm) for various periods. mRNA and protein expression were measured in freshly isolated LA FBs by qPCR and immunoblot, respectively.

Results:
Epac1 expression decreased in LA FBs within 12 hrs (-3.9 fold) of VTP onset (Fig. A). The selective Epac activator, 8-pCPT (33 μM) reduced, whereas the Epac blocker ESI-09 (1 μM) enhanced, LA FB collagen expression (Fig. B). Norepinephrine (NE, 1 μM) decreased Epac1 expression, an effect blocked by prazosin, and increased FB collagen protein production (Fig. C). Isoproterenol (ISO) increased Epac1 expression (Fig. D), an effect antagonized by ICI (β2-AR antagonist, 2 μM), but not CGP (β1-AR antagonist, 2 μM). β2-AR activation with ISO decreased collagen expression (Fig. E), an effect mimicked by salbutamol (10 μM) and blocked by ICI but not CGP. Transforming growth factor (TGF) β1 (10 ng/ml), known to be activated in HF, suppressed Epac1 expression, an effect blocked by the Smad3 inhibitor SIS3 (Fig. F).

Conclusions:
AR activation has complex effects on FBs, with NE/α-AR-activation suppressing Epac1 and increasing collagen expression, and β2-ARs having opposite effects. HF reduces LA FB Epac1 expression, likely via increased NE release from adrenergic nerve endings, along with TGF β1 activation. Epac1 signaling reduces FB collagen expression, so Epac1 downregulation in HF contributes to the atrial profibrotic milieu and may be a novel target for prevention of profibrillatory atrial remodeling.
Abstract 11927: Theracurmin Attenuates Cardiac NLRP3 Inflammasome Activation in a Rodent Model of Chronic Kidney Disease
Authors: Bugyei-Twum Antoinette , Abadeh Armin , Thai Kerri , Mitchell Melissa , Kabir Mohammed G , Connelly Kim A
Published: April 2024

Background:
Theracurmin is a novel formulation of the polyphenolic compound curcumin, which has been shown to have anti-inflammatory properties in a wide range of diseases. In chronic kidney disease (CKD), NLRP3 and inflammasome-dependent cytokines IL-1β and IL-18 have been shown to contribute significantly to disease progression and ensuing cardiovascular complications. Here, we investigate the cardio-renal effects of theracurmin in a rodent model of CKD and assess its impact on NLRP3 inflammasome activation.

Methods:
Sprague-Dawley rats were randomized to undergo sham or subtotal nephrectomy (SNx) surgery at 8 weeks of age. At 3 weeks post surgery, SNx animals were randomized to received 100mg/kg/day of theracurmin via once daily oral gavage. At 8 weeks post surgery, cardiac function was assessed, followed by LV and renal tissue collection for analysis.

Results:
Renal dysfunction, evidenced by elevated blood pressure and proteinuria, was confirmed in SNx animals. Treatment with theracurmin had no significant effect on renal function; however, an improvement in systolic blood pressure was observed (p<0.05).

Cardiac function of SNx animals was improved with theracurmin treatment. Chamber compliance, as measured by the slope of the end diastolic pressure volume relationship was improved (p<0.05). SNx-induced LV hypertrophy and fibrosis was attenuated with theracurmin treatment (p<0.05). Cardiac NLRP3 inflammasome activation, characterized by an overexpression of NLRP3 inflammasome components in SNx animals, was also attenuated in theracurmin treated animals (p<0.001).

Conclusions:
Theracurmin may be an effective compound to ameliorate cardiovascular events in the setting of CKD. The noted improvements to cardiac structure and function, albeit in the absence of significant changes to renal function, suggests a cardioprotective effect of the compound and raises the possibility of a dose-specific effect of theracurmin in the setting of CKD.
Abstract 12002: Increasing Heart Rate in Left Bundle Branch Block Results in Incomplete Relaxation and Increases Left Ventricular Diastolic Stiffness
Authors: Andersen Oyvind S , Boe Espen , Skulstad Helge , Storsten Petter , Odland Hans H , Smiseth Otto A , Remme Espen W
Published: April 2024

Introduction:
Left bundle branch block (LBBB) slows LV pressure decay and shortens diastole. At low heart rates (HR) this may not compromise filling as diastolic duration is sufficient for complete relaxation.

Purpose:
We investigated if further abbreviation of diastole at increased HR could cause incomplete relaxation, particularly in the late activated LV lateral wall; thereby increasing diastolic LV stiffness, which may cause increased filling pressure.

Methods:
We analyzed data from a study of 10 canines where HR was increased from 120 to 140 by atrial pacing before and after induction of LBBB. Ventricular and pericardial pressures, LV volume and regional segment lengths (SL) were measured. Global diastolic stiffness was calculated from end diastolic (ED) transmural LV pressure-volume (PV) relations and regional stiffness from pressure-SL relations in septum and lateral wall. A mathematical model was used to estimate the increase in filling pressure due to incomplete relaxation at HR 160 and 180.

Results:
In LBBB,
tau
was prolonged and diastole abbreviated at both HR 120 and 140, compared to baseline (Fig. 1). Increased HR during LBBB stiffened the ventricle, seen as an upward shift of the ED PV relation by 1.4±1.7 mmHg (±SD), (p=0.03) whereas no shift (-0.9±1.5 mmHg) (NS) was seen at baseline (Fig. 2). Regional ED P-SL relations showed a larger upward shift of the lateral wall (1.1±1.8 mmHg) and hence a more pronounced stiffening compared to the septum (0.6±1.5 mmHg) (p<0.05), indicating more delayed lateral wall relaxation. Mathematical estimation showed an increase in filling pressure of 7 and 16 mmHg due to further diastolic abbreviation at HR 160 and 180, respectively.

Conclusions:
LV diastolic stiffness is increased at high heart rates in LBBB due to incomplete relaxation, particularly of the late activated LV lateral wall. Diastolic stiffening by increased HR may lead to exercise intolerance and dyspnoea in LBBB patients due to elevated filling pressure.
Abstract 12052: Myocardial Extracellular Matrix Expansion Detected With Cardiac MRI: A Biomarker of Cardiomyopathic Disease in Duchenne Muscular Dystrophy
Authors: Soslow Jonathan H , Damon Stephen M , Crum Kimberly , Lawson Mark , Slaughter James C , Xu Meng , Arai Andrew E , Sawyer Douglas B , Parra David A , Damon Bruce M , Markham Larry W
Published: April 2024

Introduction:
Duchenne muscular dystrophy (DMD) cardiomyopathy is a progressive disease for which standard heart failure therapies have limited efficacy. Disease-specific therapies are needed that can be initiated before irreversible myocardial damage ensues. In order to evaluate therapeutic efficacy, surrogate endpoints other than ejection fraction must be found.

Hypothesis:
The study hypothesis is that T1 and extracellular volume fraction (ECV) mapping using cardiac magnetic resonance imaging (CMR) can detect diffuse extracellular matrix expansion in DMD patients with normal left ventricular ejection fraction (LVEF) and without late gadolinium enhancement (LGE).

Methods:
28 DMD and 11 healthy control participants were prospectively enrolled. CMR using a modified Look-Locker (MOLLI) sequence was performed before and after contrast administration. T1 and ECV maps of the mid left ventricular myocardium were generated and regions of interest were contoured using the standard 6-segment AHA model. Global and segmental values were compared between DMD and controls using a Wilcoxon rank-sum test.

Results:
DMD participants had significantly higher mean native T1 compared with controls (1045ms vs 988ms, p<0.001) (Fig 1A). DMD participants with normal LVEF and without evidence of LGE also demonstrated elevated mean native T1 (1036ms vs 988ms, p<0.001, and 1039ms vs 988ms, p=0.001) (Fig 1C, 1E). Mean post-contrast T1 values were not significantly different between DMD participants and controls. DMD participants had a significantly greater mean ECV than controls (0.31 vs 0.24, p<0.001), even in the settings of normal LVEF (0.29 vs 0.24, p<0.001) and negative LGE (0.30 vs 0.24, p<0.001) (Fig 1B, 1D, 1F).

Conclusions:
DMD participants have elevated native T1 and ECV in left ventricular myocardium, even in the setting of normal LVEF and in the absence of LGE. T1 and ECV mapping in DMD have potential to serve as surrogate cardiomyopathy outcome measures for clinical trials.
Abstract 12122: Persistence With Antiarrhythmic Agents in Atrial Fibrillation: Insights From the Veterans Health Administration
Authors: Jackevicius Cynthia , Turakhia Mintu , Essebag Vidal , Pilote Louise , Glorioso Thomas , Tu Jack V , Tsadok Meytal , Eisenberg Mark J , Atzema Clare , Lu Lingyun , Rahme Elham , Humphries Karin H , Ho P. Michael
Published: April 2024

Background:
There is limited information on patterns of persistence with antiarrhythmic drugs (AADs) in atrial fibrillation (AF). Nonpersistence may represent failure of AADs or patient/physician choice, therefore, we characterized AAD persistence patterns following discharge in patients admitted to the hospital with AF.

Methods:
This retrospective cohort study of patients with AF, diagnosed on index AF admission in the Veterans Health Administration from 2001-2010 used national inpatient, outpatient, pharmacy claims, and vital status data to identify patients and characterize persistence. We identified prescriptions for all initial AAs dispensed after AF diagnosis. Patients were considered nonpersistent if they had >30-day gap in filling a repeat AAD prescription.

Results:
Of 206,331 patients with AF, 43,262 (21%) received an AAD, age was 68.1±10.4 years, 98% were male, and CHA2DS2-VASc score was 2 (IQR: 1-3). Patients were followed for 2 years after their index AAD prescription. Among AAD-treated patients, most received amiodarone (68%). In the 2 years after their first AAD was dispensed, 43% discontinued their AAD. The lowest rates of nonpersistence were with dofetilide (29%) and sotalol (33%). Median time to nonpersistence was 143 days (IQR 90, 289). Of patients who were nonpersistent (>30-day gap), 46% restarted the same AAD, 7% switched to a different AAD, 33% switched to a rate control strategy, and 14% stopped the AAD strategy completely.

Conclusion:
Among patients with AF, 4 in 10 patients are nonpersistent with their initial AAD. Nearly 50% of patients restart their same AAD after nonpersistence, suggesting intermittent medication use likely due to patient nonadherence. One-third of patients who had initiated a rhythm control strategy with an AAD switched to a rate control strategy, indicating possible AAD failure. Given the magnitude of nonpersistence, future studies on predictors and outcomes of nonpersistence with AAD in AF are needed.
Abstract 12204: Effects of Percutaneous Transluminal Pulmonary Angioplasty on Respiratory Functions in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Aoki Tatsuo , Sugimura Koichiro , Tatebe Shunsuke , Miura Masanobu , Yamamoto Saori , Yaoita Nobuhiro , Suzuki Hideaki , Sato Haruka , Satoh Kimio , Shimokawa Hiroaki
Published: April 2024

Introduction:
Percutaneous transluminal pulmonary angioplasty (PTPA) is an emerging therapeutic strategy to improve hemodynamics and prognosis of patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). However, it remains to be examined whether PTPA also improves respiratory functions in those patients.

Methods and Results:
From July 2011 to May 2015, 69 patients with inoperable CTEPH (median age 62 yrs., female 57/69 (83%)) underwent PTPA in our hospital. In 29 of them (36%), we examined respiratory functions, including %VC, FEV1.0%, %DLco, A-a DO
2
and intra-pulmonary shunt before and after PTPA procedure. Intra-pulmonary shunt was calculated using arterial and pulmonary arterial blood samples during administration of pure oxygen. A mean of 4.8 PTPA procedures were performed, and hemodynamics and respiratory functions were examined before and after the treatment. Mean pulmonary arterial pressure (41 ± 8 to 26 ± 7 mmHg, P<0.01), pulmonary vascular resistance (9.4 ± 4.0 to 4.0 ± 1.7 Wood unit), 6-min walk distance (372±120 to 472±143 meters, P<0.01) and brain natriuretic peptide (141±155 to 38±37 pg/ml, P<0.01) were significantly improved after PTPA. Furthermore, saturation of oxygen measured in room air (SaO2, 87 ± 5 to 91 ± 5%, P<0.01), A-a DO
2
(48 ± 10 to 35 ± 11 torr, P<0.01) and intra-pulmonary shunt (24 ± 7 to 21 ± 5 %, P<0.01) were also significantly ameliorated. SaO
2
and intra-pulmonary shunt before PTPA were significantly correlated (
r
2
=0.26, P<0.01). Changes in SaO
2
after PTPA were also significantly correlated with those in intra-pulmonary shunt after the procedures (
r
2
=0.40, P<0.01) (Figure). In contrast, PTPA had no significant effects on %VC, FEV1.0% or %DLco.

Conclusions:
These results indicate that PTPA improves not only pulmonary hemodynamics but also oxygenation capacity with a resultant decrease in intra-pulmonary shunt.
Abstract 12227: Early Stimulation of Fast-Conducting Endocardial Tissue Underlies Improvements in Endocardial Pacing
Authors: Hyde Eoin R , Plank Gernot , Rinaldi Christopher A , Niederer Steven A
Published: April 2024

Introduction:
Cardiac resynchronization therapy (CRT) delivered via left ventricular (LV) endocardial pacing (ENDO-CRT) is associated with improved acute haemodynamic response compared to LV epicardial pacing (EPI-CRT). The mechanisms underlying this improved response remain controversial.

Hypothesis:
We used computational electrophysiological models to test the hypotheses that the following ordered cardiac properties are advantageous to ENDO-CRT: fast endocardial conduction (FEC), inherent geometry, asymmetric transmural conduction, and tissue anisotropy.

Methods:
Cardiac activation was simulated using the mono-domain tissue excitation model in 2D canine and human, and 3D canine biventricular models. The latest activation times (LATs) for LV endocardial and biventricular epicardial tissue were calculated (LVLAT and TLAT), as well the percentage decrease in LATs for endocardial (en) vs epicardial (ep) LV pacing (defined as %dLV=100*(LVLATep- LVLATen)/LVLATep and %dT=100*( TLATep- TLATen)/TLATep respectively).

Results:
Normal canine cardiac anatomy is responsible for %dLV and %dT values of 7.4% and 5.5%, respectively. Concentric and eccentric remodelled anatomies resulted in %dT values of 15.6% and 1.3%, respectively. The 3D biventricular paced canine model resulted in %dLV and %dT values of -7.1% and 1.5%, in contrast to the experimental observations of 16% and 11%, respectively. Adding FEC to this model altered %dLV and %dT to 13.1% and 10.1%, respectively.

Conclusions:
Our results provide a physiological explanation for improved response to ENDO-CRT. We predict that patients with viable fast-conducting endocardial tissue and/or distal Purkinje network, as well as concentric remodelling, are more likely to benefit from reduced ATs and increased synchrony arising from endocardial pacing.