bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13337: Heart-type Fatty Acid Binding Protein and High-Sensitivity Troponin T Are Myocardial Damage Markers That Could Predict Adverse Clinical Outcomes in Patients With Peripheral Artery Disease
Authors: Yoichiro Otaki , Watanabe Tetsu , Takahashi Hiroki , Funayama Akira , Yamaura Gensai , Arimoto Takanori , Shishido Tetsuro , Miyamoto Takuya , Kubota Isao
Published: April 2024

Background:
Despite many recent advances in endovascular therapy (EVT), peripheral artery disease (PAD) is an increasing health problem with high mortality. Heart-type fatty acid-binding protein (H-FABP) and high-sensitivity troponin T (hsTnT) are markers of ongoing myocardial damage and have been reported to be useful indicators for future cardiovascular events. However, it remains to be determined whether H-FABP and hsTnT can predict adverse clinical outcomes in patients with PAD.

Methods and Results:
We enrolled 208 de novo PAD patients who underwent EVT. Serum H-FABP and hsTnT were measured in all patients before EVT. During the median follow up period of 694 days, there were 40 major adverse cardiovascular and cerebrovascular events (MACCEs) including all-cause deaths, and re-hospitalizations due to cardiovascular and cerebrovascular diseases and amputations. H-FABP and hsTnT were found to be higher in patients with critical limb ischemia (CLI) compared to those without this condition. Multivariate Cox proportional hazard regression analysis revealed that both H-FABP and hsTnT were independent predictors of MACCEs after adjustment for confounding factors. Kaplan-Meier analysis demonstrated that patients in the highest tertile according to H-FABP levels, as well as those in the highest hsTnT tertile, were at greatest risk for MACCEs. The net reclassification index was significantly improved by the addition of H-FABP as well as the addition of hsTnT to traditional risk factors.

Conclusion:
The myocardial damage markers H-FABP and hsTnT were increased in PAD patients with CLI and could predict MACCEs in PAD patients.
Abstract 13545: ST2 in Heart Failure With Preserved Ejection Fraction
Authors: AbouEzzeddine Omar F , McKie Paul M , Dunlay Shannon M , Stevens Susanna R , Felker G M , Borlaug Barry A , Chen Horng H , Tracy Russell P , Braunwald Eugene , Redfield Margaret M
Published: April 2024

Introduction:
In vitro, ST2 is a marker of myocyte stress and inflammation but in vivo, there is no trans-cardiac ST2 concentration step-up to support cardiac ST2 activation in human heart failure (HF) calling into question the source of ST2 in HF. While ST2 is predictive of adverse outcomes in HF, the relationship between ST2 and key pathophysiologic domains in HF with preserved ejection fraction (HFpEF) is not well characterized.

Hypothesis:
ST2 levels increase in proportion to the severity of left ventricular (LV) remodeling and dysfunction in HFpEF.

Methods:
At enrollment, patients (n=174) from the RELAX trial testing sildenafil in HFpEF had serum ST2 levels measured and underwent assessment of pathophysiologic domains including congestion, cardiac structure and function, exercise performance (peak oxygen consumption (VO2)) and biomarkers of neurohumoral activation (NT-proBNP, aldosterone, endothelin-1), renal dysfunction (cystatin-C), fibrosis (pro-collagen III N-terminal peptide [NTP], C-telopeptide for type I collagen [CITP]), inflammation (high-sensitivity CRP [hsCRP]) and myocardial necrosis (high-sensitivity troponin-I [hsTnI]). Analysis adjusted for sex, a covariate associated with ST2 levels in normal persons.

Results:
See table. ST2 was associated with greater congestion, worse right ventricular (RV) pressure overload and dysfunction, lower peak VO2 and biomarkers of neurohumoral activation, renal dysfunction, fibrosis and myocardial necrosis and tended to be associated with systemic inflammation (hsCRP). ST2 was not associated with LV structure or LV systolic or diastolic function.

Conclusions:
In HFpEF, ST2 was associated with measures of right sided congestion, RV overload and dysfunction, exercise intolerance and other systemic markers of more advanced HF but not with LV structure or LV systolic or diastolic function. These data suggest that mechanisms distinct from LV stress stimulate ST2 activation in HFpEF.
Abstract 13621: Integrating Metabolomics and Genomics Uncovers Novel Pathways and Genetic Signatures Influencing Hydrochlorothiazide Blood Pressure Response: A Genetic Response Score for Hydrochlorothiazide Use
Authors: Shahin Mohamed H , Rotroff Daniel M , Webb Amy , Gong Yan , Langaee Taimour , McDonough Caitrin W , Beitelshees Amber L , Garrett Timothy , Gums John G , Motsinger-Reif Alison , Chapman Arlene B , Turner Stephen T , Boerwinkle Eric , Frye Reginald F , Scherer Steven E , Sadee Wolfgang , Fiehn Oliver , Cooper-DeHoff Rhonda M , Kaddurah-Daouk Rima , Johnson Julie A
Published: April 2024

Introduction:
Hydrochlorothiazide (HCTZ) is among the most commonly prescribed antihypertensives in the US, yet <50% of HCTZ treated patients achieve blood pressure (BP) control.

Hypothesis:
Integrating metabolomic and genomic profiles of HCTZ treated patients could identify novel pathways/biomarkers for optimizing the use of HCTZ.

Methods:
Primary analysis included 228 white hypertensives treated with HCTZ from the Pharmacogenomic Evaluation of Antihypertensive Response (PEAR) study. Genotyping was determined via Illumina Omni 1M-Quad Chip and untargeted metabolomics was performed on baseline fasting plasma samples using a GC-TOF MS platform. Pathway analysis was used to integrate metabolites significantly associated with HCTZ BP response (FDR<.05) and genetic signals at p<5x10-5 from HCTZ BP genome-wide analysis. Replication was conducted in another 212 white HCTZ treated patients. Replicated genetic signals were used to create a BP response score by summing their BP lowering alleles. We validated this score by testing it in 196 white HCTZ treated patients in the Genetic Epidemiology of Responses to Antihypertensives (GERA) study.

Results:
Thirteen metabolites were significantly associated with HCTZ systolic BP (SBP) and diastolic BP (DBP) responses (FDR<.05). Metabolomics-genomics integration revealed significant metabolites along with rs2727563 PRKAG2, rs12604940 DCC, and rs13262930 EPHX2, in the netrin signalling pathway (p=1x10-5), as potential markers significantly influencing HCTZ BP response. We successfully replicated those 3 genetic signals and added their alleles to create a response score which explained 11.3% and 11.9% of the variability to HCTZ SBP and DBP responses, respectively. We found that patients carrying one “response” allele had a significantly worse response than carriers of six alleles (ΔSBP/ΔDBP: -1.5/1.2 vs -16.3/-10.4 mmHg, respectively, SBP score p=1x10-8 and DBP score p=3x10-9). We further validated this response score by testing it in the GERA (DBP score p=0.03, SBP score p=0.07).

Conclusion:
This study highlights the power of using different omics to identify novel pathways/biomarkers of drug response, and suggests that PRKAG2, DCC and EPHX2 might be important determinants of HCTZ BP response.
Abstract 13635: Atorvastatin for the Prevention of Major Vascular Events in Patients Undergoing Non-Cardiac Surgery: The LOAD-Pilot Randomized Clinical Trial
Authors: Berwanger Otavio , Soares Rafael M , Ikeoka Dimas T , Paisani Denise M , Silva Beatriz G , Bernardez-Pereira Sabrina , Barros Pedro G , Devereaux Philip J , Lopes Renato D
Published: April 2024

Background:
There is not a single established effective and safe intervention to prevent major perioperative vascular complications that commonly occur in the first 30 days after noncardiac surgery.

Hypothesis:
We evaluated the feasibility of a multicenter randomized controlled trial (RCT) testing the perioperative effects of statins.

Methods:
This is a double blind, placebo-controlled RCT testing a short course of atorvastatin 80mg before surgery, followed by 40mg 12 hours after surgery and then 40mg/day for 7 days in patients undergoing noncardiac surgery who were at risk of a major perioperative vascular complication. The primary outcome (major vascular events) was a composite of all-cause mortality, nonfatal myocardial infarction, MINS (myocardial injury after noncardiac surgery) without myocardial infarction and nonfatal stroke at 30 days after randomization. All analysis followed the intention-to-treat principle.

Results:
We enrolled 587 patients from 30 centers in Brazil. Mean age was 66.6 years, 37.1% were males, 22.0% had previous cardiovascular disease, 50.2% had diabetes and 89.7 % had hypertension. The majority of participants underwent general (35.9%), orthopedic (30.0%), gynecologic (8.4%), urologic (7.3%), and vascular (6.6%) surgery. A total of 51 out of 300 patients (17.0%) suffered a major vascular complication in the atorvastatin group compared to 49 out of 287 patients (17.1%) in the control group at 30 days (hazard ratio [HR] 1,02; 95% confidence interval (CI) 0.68 to 1.52; P = 0.93). No significant effect was observed on the 30-day secondary outcomes of death or myocardial infarction (8.0% versus [vs.] 7.7%, respectively; HR 0.94; 95% CI 0.52 to 1.70; P = 0.84), myocardial infarction (3.7% vs. 4.5%, respectively; HR 0.84; 95% CI 0.37 to 1.93; P = 0.68), MINS (14.0% vs.15.0%; HR 0.94; 95% CI 0.53 to 1.67; P = 0.84), and all-cause mortality (4.7% vs. 4.5%; HR 1.22; 95% CI 0.53 to 2.78; P = 0.64).

Conclusions:
The LOAD Trial confirms that a multicenter perioperative statin trial is feasible and highlights the need for large RCTs to establish effective and safe interventions. The study also suggests that effects of a perioperative statin on major vascular complications are, at best, moderate in size, questioning the robustness of prior data.
Abstract 13643: Impact of Aortic Valve Repair and Valve-sparing Procedures on the Mitral Annular Geometry Assessed by 3-dimensional Transesophageal Echocardiography
Authors: Page Maude , Laflamme Maxime , De Meester Christophe , Amzulescu Mihaela , De Kerchove Laurent , El Khoury Gebrine , Pasquet Agnès , Vanoverschelde Jean-Louis
Published: April 2024

Background:
Annular non-planarity, the "saddle-shape" of the mitral valve (MV) annulus, plays a role in minimizing leaflet stress and preserving valve function. Aortic valve (AV) repair/sparing procedures are increasingly used to treat aortic regurgitation (AR). The impact of these procedures on MV geometry and function is unknown.

Methods:
2D and 3D transesophageal echocardiography (TEE) of the MV was acquired pre-operatively and immediately after surgery in 30 patients with severe AR and/or aortic root dilatation (Group 1 (n=10): bicuspid AV undergoing AV repair and valve-sparing root replacement with AV reimplantation; Group 2 (n=10): tricuspid AV undergoing AV repair and AV reimplantation; Group 3 (n=10): isolated AV cusp repair) and in 10 controls (Group 4). MV morphology was assessed by dedicated quantification software (fig. 1).

Results:
Comorbidities were similar in all groups. Groups 1, 2 and 3 had increased LV end-diastolic volumes compared to group 4 (214±90, 193±56, 180±55 vs. 86± 28ml for groups 1, 2, 3 and 4, respectively; p<0.001); LVEF was similar (59.5 ± 6.2%). The baseline dimensions of the ventriculo-aortic junction and sinuses of Valsalva were larger in groups 1 and 2 vs. groups 3 and 4 (p<0.0001). AV and MV parameters are summarized (table). Pre-operative MV parameters did not differ from those of normal subjects. The annular height and annular height to commissural width ratio (AHCWR) significantly decreased after surgery in groups 1 and 2, as did the tenting area. Significant changes in the coaptation depth and mitro-aortic angle were only found in group 1.

Conclusions:
AV repair/sparing procedures alter the MV geometry, including the non-planarity of the annulus and the depth of coaptation of the leaflets, especially among patients with a bicuspid AV undergoing AV reimplantation. These alterations could have long-term implications on MV function.
Abstract 13695: Global Electrical Heterogeneity Risk Score Predicts Sudden Cardiac Death in the General Population
Authors: Tereshchenko Larisa G , Waks Jonathan , Sitlani Colleen , Soliman Elsayed , Kabir Muammar , Ghafoori Elyar , Henrikson Charles , Sotoodehnia Nona , Biering-Sørensen Tor , Agarwal Sunil , Siscovick David , Post Wendy , Solomon Scott , Buxton Alfred , Josephson Mark E
Published: April 2024

Background:
The majority of sudden cardiac deaths (SCDs) in the general population occur in asymptomatic individuals. Our goal was to develop and validate a SCD risk score for use in the general population.

Methods:
The prospective Atherosclerosis Risk in Communities (ARIC) study [n=15,366; age 45-64 yr; 45% male; 73% white; 5% prevalent coronary heart disease (CHD), median 14 yrs of follow-up] was used for risk score development. ECG markers of global electrical heterogeneity (GEH) [sum absolute QRST integral (SAI QRST), spatial ventricular gradient (SVG), and spatial QRS-T angle] were measured on standard 12-lead ECGs and abnormal values were derived using the Youden index. Competing risk models were evaluated using C-statistics, integrated discrimination improvement, net reclassification improvement (NRI), and Akaike Information Criterion. Internal cross-validation was performed in 5 partitions. Adjudicated SCD was the primary outcome.

Results:
Overall SCD incidence was 1.51 (95% CI 1.35-1.69) per 1,000 person-yrs. The most accurate risk model included gender-, race-, and CHD-specific GEH ECG parameters [SAI QRST, spatial QRS-T angle, and SVG direction (azimuth and elevation)], demographics (sex, race, age≥55 y), clinical characteristics (CHD, diabetes, hypertension, stroke), QTc interval, and 1 interaction term (abnormal SVG azimuth in age≥55 yrs). C-statistic was 0.842 (95% CI 0.814-0.859) in the whole cohort and ranged 0.782-0.866 in 5 cross-validation partitions. The risk score classified 10-yr SCD risk as low (0 to <1%), intermediate (1-10%), and high (>10%) in 65.5%, 32.3%, and 2.2% of participants, respectively. With addition of GEH ECG markers to clinical/demographic factors C-statistic increased from 0.813 to 0.837 (p=0.004), 28/311 (9%) of participants were appropriately reclassified from intermediate to high risk, and only 4/311 (1.3%) were inappropriately reclassified from high to intermediate risk. NRI was 13.3% (P<0.001). The score was highly specific (98.2%) for SCD, and predicted SCD better than non-sudden cardiac death. Negative predictive value for SCD was up to 99.5%.

Conclusion
A risk score using basic clinical characteristics and novel GEH ECG parameters accurately predicted SCD in the general population.
Abstract 13702: Serum Albumin Predicts Mortality in Patients With Pulmonary Arterial Hypertension
Authors: Jentzer Jacob C , Morris Jacqueline , Costabile Chelcie , Dardari Zeina , Batal Omar , Mathier Michael
Published: April 2024

Introduction:
Low serum albumin predicts adverse outcomes in heart failure, reflecting poor nutritional status, liver dysfunction and systemic inflammation. The predictive value of albumin for mortality is not well-described in pulmonary arterial hypertension (PAH).

Hypothesis:
Low serum albumin will significantly predict increased mortality in patients with PAH.

Methods:
We constructed a database of 273 WHO group 1 PAH patients followed at our center from 03/2001 through 08/2008, including echocardiography, invasive hemodynamics, laboratory data and mortality outcomes. Serum albumin levels were available in 163 patients. The association between albumin and mortality was assessed using Cox regression and Kaplan-Meier analysis.

Results:
Patients were followed for a mean of 3.6 ± 2.6 years. On univariate analysis, serum albumin significantly predicted mortality with HR = 0.746 (p = 0.01, 95% CI 0.598-0.932) per 1 g/dl increase. On multivariate analysis, serum albumin significantly predicted mortality with HR = 0.491 (p = 0.009, 95% CI 0.288-0.835) per 1 g/dl increase when adjusted for age, gender, NYHA functional class, mean right atrial pressure, Fick cardiac output, connective tissue disease, right ventricular function, right atrial systolic area and serum creatinine. Patients with serum albumin below the 25th percentile (<=3.3 g/dl) had significantly higher mortality by Kaplan-Meier curve analysis (p = 0.01 by log-rank test) despite similar clinical characteristics, when compared with patients with higher serum albumin.

Conclusion:
Higher serum albumin is an independent predictor of decreased mortality in PAH patients when adjusted for clinical, echocardiographic and hemodynamic variables. Patients with low serum albumin values had significantly higher mortality despite similar characteristics.
Abstract 13736: Mast Cell Activation During Aortic Repair Requiring Circulatory Arrest is Associated With Hemodynamic Instability and Indications of End-Organ Injury
Authors: Cheruku Sreekanth , Kertai Miklos D , Qi Wenjing , Li Yi-Ju , Hughes G. C , Mathew Joseph P , Karhausen Joern
Published: April 2024

Background:
Systemic inflammatory responses after cardiac surgery are associated with hemodynamic instability and an increased risk of end-organ injury. We recently identified mast cell activation as a critical mechanism of tissue injury, local and systemic inflammation in a rat model of circulatory arrest (CA). To test the clinical relevance of these findings, we now examined mast cell activation in patients undergoing cardiopulmonary bypass (CPB) and CA.

Methods:
After institutional review board approval, 31 patients with elective aortic arch surgery employing CPB and CA were prospectively enrolled from June 2013 until April 2015. Arterial blood samples were obtained at induction of anesthesia, on CPB when reaching target temperature, 10 minutes after CA, and after weaning from CPB. Plasma mast cell specific chymase, IL-6, TNFa, and IL-8 were measured by ELISA. Patient demographics and clinical parameters were retrieved from the electronic charting system. Statistical analysis was performed using SAS software.

Results:
Chymase levels increased with institution of CPB (delta baseline chymase: 5.59±6.29* at target temperature, 5.46±6.14* after CA, and 9.66±7.82* at end of CPB; * pg/mg plasma protein, p≤0.05). We observed no changes in TNFα at any time-point and significant changes of IL-6 and IL-8 only after end of CPB (delta baseline: 1.4±2.6pg/mg plasma protein and 10.8±6.3pg/mg plasma protein, p≤0.05). Time and area under the curve of a mean arterial pressure below 60 were significantly increased in patients with above-median chymase level vs. patients with below-median chymase levels at the end of CPB (p=0.0097 and p=0.014 respectively by 2-sample t test). Also, in these patients there was a consistent trend towards increased intraoperative phenylephrine, vasopressin, and epinephrine dose, increased postoperative lactate levels and a higher incidence of postoperative renal injury. Analysis of surgical factors revealed an association of chymase levels with higher target temperatures during CA, but not with duration of CPB or CA.

Conclusions:
We provide first evidence that significant and rapid mast cell activation occurs during cardiac surgery and is associated with a complicated intraoperative and early postoperative clinical course.
Abstract 13761: Single Nucleotide Polymorphism of Mlx Gene Causes Txnip Accumulation and Inflammasome Formation, Thereby Promoting the Development of Takayasu Arteritis
Authors: Tamura Natsuko , Maejima Yasuhiro , Isobe Mitsuaki
Published: April 2024

Introduction:
We have previously conducted genome-wide association study of Takayasu arteritis(TA) and revealed that single nucleotide polymorphism (SNP) of
MLX
,a gene encoding MLX transcription factor, was markedly associated with clinical phenotypes of TA. Recently, we also have shown that SNP of the
MLX
(rs665268), a missense mutation of
MLX
that alters the 139
th
glutamine to arginine (Q139R) on MLX facilitates the heterodimer formation of MLX with MondoA, which in turn promoting transcription of the thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of thioredoxin. However, it remains unknown how upregulation of TXNIP caused by SNP of
MLX
is associated with the pathogenesis of TA.

Hypothesis:
Accumulation of TXNIP caused by mutation of MLX-Q139R plays an important role in the development of TA.

Methods and Results:
The protein level of NLRP3, a major component of inflammasome, as well as that of TXNIP was significantly accumulated (TXNIP: 4.5 fold, NLRP3: 3.8 fold) in human aortic smooth muscle cells(hASMCs) transfected with MLX-Q139R plasmid than compared to those in transfected with wild-type MLX plasmid. Immunostaining demonstrated that both NLRP3 and TXNIP accumulated more prominently in the SMCs of aortas of TA than in normal aortas, suggesting that increased level of TXNIP by MLX-Q139R mutation is associated with accumulation of NLRP3 in hASMCs. To address the consequence of MLX-Q139R mutation on inflammatory cells, we isolated human peripheral blood mononuclear cells (hPBMCs) from TA patients and normal subjects. Treatment of IL-12 significantly enhanced the protein level of both TXNIP and caspase-1, another main component of inflammasome, in T lymphocytes differentiated from hPBMCs of TA patients compared to those from normal subjects. We conducted
in vitro
proliferation assays of hASMCs co-cultured with hPBMCs. hASMCs significantly proliferated when hPBMCs from normal subjects were co-cultured, and this proliferation was more prominent when hASMCs were co-cultured with hPBMCs from TA patients.

Conclusion:
The increase of TXNIP caused by MLX-Q139R mutation promotes inflammasome formation in both hASMCs and hPBMCs, thereby facilitating proliferation of hASMCs, a pathological manifestation seen in the aortas of TA.
Abstract 13809: Serial Paraoxonase-1-associated Serum Arylesterase Activity and Outcomes in Ambulatory Patients With Heart Failure
Authors: Hammadah Muhammad , Kalogeropoulos Andreas P , Georgiopoulou Vasiliki , Weber Malory , Wu Yuping , Butler Javed , Tang W.H.Wilson
Published: April 2024

Introduction:
Decreased arylesterase (ArylE) activity of paraoxonase-1, a HDL-associated protein with anti-inflammatory and antioxidant properties, has been associated with increased risk of cardiac events in ischemic heart failure (HF) patients. However, the change of ArylE activity over time and its association with HF adverse outcomes has not been reported.

Methods:
We examined the association between baseline and follow up serum ArylE activity and HF outcomes (death, cardiac transplantation or ventricular assist device implantation) in 304 patients with HF enrolled in the Atlanta Cardiomyopathy Consortium, a prospective cohort study in the metropolitan Atlanta GA area from 1/2008 to 7/2009. ArylE activity was assessed on enrollment for all patients, and for 152 patients after 1 year of follow up. Significant drop in ArylE activity on follow up was defined as a drop of ≥25% vs. baseline levels.

Results:
In our population (age 56.5±12 years, male 63.9%, CAD 39.1%, EF 30±15 %), mean baseline and follow up ArylE activity levels were 110.5 ± 29.8 μmol/min/ml and 105.2±27.7 μmol/min/ml, respectively. Mean ArylE activity change between follow up and baseline levels was -5.9 ± 28.6 μmol/min/ml, p = 0.015. After mean follow up of 2.8 ± 1.1 years, 53 events were reported. Low baseline ArylE activity was associated with increased risk of adverse HF outcomes [HR (95CI%) for lowest tertile vs highest tertile of 2.6 (1.3-5.5), p=0.01] (Figure A). This association remained significant after adjustment for age, gender, diabetes, creatinine clearance and CAD. Patients who had significant drop in ArylE activity (≥25% of baseline levels, n=18), had significantly increased risk of HF events [HR(95%CI) of 4.9 (1.6-14.6), p=0.005], even after adjustment for baseline levels of ArylE activity (Figure B).

Conclusions:
Reduced baseline ArylE activity and decreased levels on follow up are associated with adverse outcomes in stable outpatients with HF.
Abstract 13879: Clinical Features and Prognosis of Patients With Left Ventricular Noncompaction Cardiomyopathy: A Comparison Between Infantile and Juvenile Types
Authors: Takasaki Asami , Ozawa Sayaka , Miyao Nariaki , Nakaoka Hideyuki , Ibuki Keijiro , Hirono Keiichi , Yoshimura Naoki , Ichida Fukiko
Published: April 2024

Introduction:
Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by a left ventricle with a prominent trabecular meshwork. Long-term prognosis of LVNC has not been elucidated yet.

Purpose:
The aim of this study is to clarify the difference between infantile and juvenile cases and identify the risk factor of poor prognosis of LVNC in the largest series to date.

Methods:
Based on nationwide surveys of LVNC in Japanese children, we compared the clinical features and anatomical properties of infantile cases of LVNC (< 2 years: 85 cases) with that of juvenile cases (2-15 years: 73 cases). In addition to the standard noncompacted to compacted layer (N/C) ratio, we developed an echocardiographic criteria which represents an average of N/C ratios in five wall segments to estimate the severity of LVNC.

Results:
The duration of follow-up ranged from 15 days to 22 years (median 5 years). Although most patients in the infantile group had clinical signs of heart failure at initial presentation (70.1%), the majority of juvenile cases were asymptomatic and identified when screened for cardiac abnormalities, such as ECG screening (55.8%). WPW syndrome was higher in both groups (infantile group: 9.7%, juvenile group: 10.0%), the incidence of LBBB and VT was lower than those reported in adults. On echocardiography, the maximum N/C ratio was observed at the apex in both groups. Neither noncompaction score nor N/C score was significantly different between groups. Left ventricular ejection fraction (LVEF) at initial presentation was significantly lower in the infantile group than in the juvenile group. Although survival analysis showed poor prognosis in the infantile group, the significant risk factor was LVEF below 50% (p = 0.0004, hazard ratio = 9.0), rather than age of onset.

Conclusions:
LVNC in both infantile and juvenile groups showed poor prognosis when correlated with depressed LVEF at initial presentation.
Abstract 13881: Cardiac Progenitor Cell Infusion in Patients With Univentricular Heart Diseases in Heart Failure With Preserved Ejection Fraction
Authors: Ousaka Daiki , Goto Takuya , Ishigami Shuta , Ohtsuki Shinichi , Kasahara Shingo , Sano Shunji , Oh Hidemasa
Published: April 2024

Backgrounds:
The clinical outcomes of heart failure with reduced and preserved ejection fraction (HFrEF and HFpEF) after staged palliations in patients with univentricular heart disease remain unknown as is the question whether cardiosphere-derived cell (CDC) transfer may have impact on either type of cardiac dysfunction.

Purpose:
We sought to characterize the heart failure patients, include HFrEF and HFpEF, with single ventricular physiology and investigate the clinical responsiveness after CDC therapy.

Methods:
Forty-three patients, aged 2.2±1.4 years, undergoing staged shunt procedures were divided into two groups by cardiac function based on cMRI (HFrEF: EF<40%, n=30; HFpEF: EF>40%, n=13).

Results:
Compared with HFpEF patients, HFrEF patients showed increased cardiac volume (P=0.02) and mass index (P=0.04), those were associated with reduced global circumferential strain in HFrEF compared with HFpEF (P=0.0004). There was no difference in the incidence of late gadolinium enhancement detected by cMRI in both groups (20% in HFrEF and 15% in HFpEF). When patients underwent staged shunt procedures, HFpEF group had significant reduction in EF (P=0.03) and atrial strain (P=0.047), resulting in increase in Tei index 1 month after palliation (P=0.02). To investigate whether CDC infusion may affect the cardiac function in these two types of HF, patients were subjected to receive CDC injection 1 month post palliation. In contrast to HFpEF group, HFrEF patients demonstrated a marked improvement in EF (P=0.0006), right ventricular elastance (P=0.0005) 3 months after CDC infusion. Similarly, diastolic function improvements were found in CDC-treated HFrEF group but HFpEF patients as shown by increased atrial fractional area change (P=0.01) and reduced E-wave/e’sr (P=0.049). However, patients with HFpEF showed no improvement in diastolic function but significantly reduced dP/dt at 3 months (P=0.04). These beneficial effects by CDCs could not be seen in remaining 20 patients who were assigned to treat as palliation alone without CDC injection.

Conclusions:
HFpEF is common in univentricular heart diseases and that may have early perioperative right ventricular dysfunction and could be CDC therapy-resistant leading to latent heart failure.
Abstract 13935: Predictors for the Improvement of Cardiac Symptoms After Renal Stenting; Multicenter Retrospective (PREMIERE) Registry Study
Authors: Narishige Yuri , Kawarada Osami , Sakamoto Shingo , Harada Koichiro , Noguchi Teruo , Ogawa Hisao , Yasuda Satoshi
Published: April 2024

Background:
There have been limited data available regarding response of renal artery stenting for cardiac disturbance syndrome (CDS) in atherosclerotic renal artery stenosis (ARAS) patients. The PREMIERE registry was a multicenter, retrospective study to clarify predictors for the improvement of cardiac symptoms after renal stenting.

Methods and Results:
We enrolled 51 ARAS patients with CDS undergoing successful renal artery stenting (age 73.3±1.43, 30 males) from 11 hospitals in Japan between January 2000 and August 2015. The improvement of cardiac symptoms evaluated by NYHA functional class was observed in 86.3% (44 patients). According to a univariate analysis, eGFR and echocardiographic indices such as interventricular septal wall thickness (IVS) and early transmitral flow velocity were significantly (P<0.05) associated with the improvement of cardiac symptoms. Stepwise multivariate analysis using those variables with P<0.15 identified IVS as an independent predictor (Odds ratio 0.29; P=0.039). According to receiver operating characteristic (ROC) curve analysis, IVS cut off of 11.9 mm provided the best predictive value with a sensitivity of 78.4% and a specificity of 79.5% (Figure).

Conclusion:
The present multicenter, retrospective study demonstrated that echocardiographic indice of IVS was a potential clinical predicator for the improvement of cardiac symptoms after renal artery stenting.
Abstract 13966: Left-sided Rib Fractures During Cardiopulmonary Resuscitation Are Associated With Better Coronary Perfusion Pressure in a Pig Model of Cardiac Arrest
Authors: Debaty Guillaume , Bartos Jason A , Matsuura Timothy R , Rees Jennifer N , Lick Michael , McKnite Scott H , Yannopoulos Demetris
Published: April 2024

Introduction:
Since its inception, concerns have been raised about the complications associated with cardiopulmonary resuscitation (CPR). To date, there is no evidence that these complications are linked to worsened outcomes.

Hypothesis:
The aim of this study was to describe the hemodynamic effect of rib fractures during automated mechanical CPR in a porcine model of cardiac arrest.

Methods:
We conducted a prospective observational study between November 2013 and November 2014. Animals were included if they developed rib fractures during CPR but prior to injection of any drugs. To determine the exact timing of the broken rib, only pigs with obvious thorax deformation were included. An autopsy was performed at the end of each study. A group of 11 control animals without broken ribs was also included to compare data between groups. Time points in the control group matched those in the broken rib group. Data are presented as mean ± standard error of mean.

Results:
Broken ribs were observed during CPR in 15 pigs at a mean time of 97 ± 10 sec after the start of CPR (12 with left chest deformation and 3 with right chest). The mean number of broken ribs was 4 ± 0.2. In the left-sided broken rib group, coronary perfusion pressure (CPP) and systolic blood pressure (SBP) increased after rib fractures (p for trend <0.001). EtCO2 increased similarly in the left broken rib group from 31 ± 5 prior to rib fracture to 43 ± 3, 46 ± 4 and 49 ± 4 at 10, 30 and 60 seconds after rib fracture, respectively (p for trend <0.001). This increase was not observed in the right-sided broken rib group (Fig 1). Return of spontaneous circulation was achieved in 12/12 animals with left broken ribs, 1/3 animals with right broken ribs and 6/11 animals in the control group (p=0.007).

Conclusion:
During CPR, left rib fractures improved CPP, SBP and EtCO2 compared to control animals. This may suggest direct cardiac compression as a means to the effect. Further studies are warranted to assess the impact on survival.
Abstract 13989: Duration of Interventricular Septal Shift Predicts Clinical Outcome in Patients With Precapillary Pulmonary Hypertension: A CMR Study
Authors: Giannakoulas George , Mouratoglou Sophia-Anastasia , Kallifatidis Alexandros , Hadjimiltiades Stavros , Pitsiou Georgia , Stanopoulos Ioannis , Karvounis Haralambos
Published: April 2024

Introduction:
Right ventricular pressure overload results in interventricular septal (IVS) shift towards the left ventricle in patients with precapillary pulmonary hypertension (pPH).

Hypothesis:
The duration of IVS shift towards left ventricle during the cardiac cycle, as expressed by a novel marker called curvature duration index (CDi), predicts clinical outcome in pPH patients.

Methods:
This was a prospective study. All patients underwent cardiac magnetic resonance (CMR, Avanto Siemens 1,5T). CMR parameters of right ventricular function and dimensions were assessed. CDi (duration of IVS shift towards left ventricle x 100/cardiac cycle duration) was defined in the short-axis view at the level of papillary muscles (Figure 1). Time from enrollment to clinical failure (hospitalization due to pPH, initiation of parenteral prostanoid therapy, atrial septostomy or death) was recorded.

Results:
Our study included 36 consecutive patients (28 women, mean age 50.6±13.8 years) with pPH. Over a median follow-up period of 20.4 months (IQR 16.3-24.6 months) 14 clinical events were observed. In Cox proportional hazard analysis, only baseline CDi was significantly related to the composite event (HR 1.05, 95% CI 1.01-1.08, p=0.016). ROC curve analysis showed that the optimal cut-off value of CDi which predicted events was 66.7%. Kaplan-Meier survival analysis showed that CDi ≥66.7% was associated with a 9-fold increased risk for clinical failure (Figure 2).

Conclusions:
Ventricular septal shift towards left ventricle lasting for more than the 2/3 of the cardiac cycle is associated with worse prognosis in pPH.
Abstract 14156: Airway Gene Delivery of Serca2a Ameliorates Chronic Pulmonary Hypertension in a Large Animal Preclinical Model
Authors: Aguero Jaume , Ishikawa Kiyotake , Hadri Lahouaria , Santos-Gallego Carlos G , Fish Kenneth M , Hammoudi Nadjib , Ibanez Borja , Garcia-Alvarez Ana , Zsebo Krisztina , Plataki Maria , Fuster Valentin , Leopold Jane A , Hajjar Roger J
Published: April 2024

Downregulation of sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a) in the pulmonary vasculature leads to perturbations in Ca2+ homeostasis, endothelial dysfunction, and transition of pulmonary artery smooth muscle cells from a contractile to a proliferative phenotype. To assess the feasibility and benefits of sustained pulmonary vascular SERCA2a gene transfer, we created a model of chronic post-capillary PH in Yorkshire swine by partial pulmonary vein banding. Development of chronic PH was hemodynamically confirmed, and animals were randomized to intratracheal administration of adeno-associated virus type 1 (AAV1) carrying the human SERCA2a gene (n=10, AAV1.SERCA2a group) or Saline (n=10). Transduction efficacy after intratracheal delivery of AAV1 was confirmed by β-galactosidase detection in the distal pulmonary vasculature and significant overexpression of SERCA2a protein at the distal airway and small pulmonary arteries. Two months after gene delivery, disease progression was prevented in AAV1.SERCA2a treated animals as assessed by mean pulmonary pressure (29[5] vs 54[20] mmHg, p=0.027, Figure) and pulmonary vascular resistance index (3.2[2.2] vs 10.3[7.1] Wood units*m2, p=0.020) along with decreased small vessel remodeling in the AAV1.SERCA2a group (p<0.05). RV ejection fraction (61[7] vs 50[7] % units, p=0.014) was preserved and improvement of RV end-diastolic pressure-volume relationship (0.12[0.08] vs 0.28[0.07] mmHg/ml, p=0.08) in AAV1.SERCA2a treated pigs versus Saline. In conclusion, airway-based delivery of AAV vectors to the pulmonary arteries is feasible, efficient, and safe in a clinically relevant chronic PH model. Selective vascular SERCA2a overexpression results in beneficial effects on pulmonary hemodynamics and RV performance, and may offer therapeutic benefit by modifying fundamental pathophysiology in pulmonary vascular diseases.
Abstract 14282: Cold Saline Infusion is an Effective Method to Achieve Intra-Cardiopulmonary Resuscitation Therapeutic Hypothermia
Authors: Tsangaris Adamantios , Matsuura Timothy R , Lick Michael C , Bartos Jason A , McKnite Scott H , Chandra Shekar Kadambari , Rees Jennifer N , Yannopoulos Demetris
Published: April 2024

Objective:
Therapeutic hypothermia (TH) is thought to improve neurologically intact survival when applied after return of spontaneous circulation (ROSC) is achieved in patients who suffer a cardiac arrest. Intra-CPR cooling may accelerate the time to reach TH and thus enhance its neurological benefit. Sodium nitroprusside enhanced cardiopulmonary resuscitation (SNPeCPR), consisting of active compression decompression (ACD) with an impedance threshold device (ITD), abdominal binding, and bolus doses of SNP, has been shown to accelerate intra-CPR cooling compared to standard CPR. The aim of this study is to compare the rate of cooling achieved during CPR using various cooling methods as part of the resuscitation effort.

Methods:
This study included 24 intubated and anesthetized swine. Brain temperature probes were surgically placed. After induction of ventricular fibrillation (VF), animals were randomized to one of the following groups: 500cc cold saline infusion (group A), 500cc cold saline infusion plus surface cooling with ice packs (group B), surface cooling with ethanol soaked towels (group C) or control (group D). After 10 minutes of VF, ACD-ITD CPR was initiated. One minute after the initiation of CPR, the randomized intervention was initiated and abdominal binding was applied. SNP (2 mg) was administered at minutes 1, 4 and 8. Animals were defibrillated at minute 10.

Results:
Group A and Group B had the fastest decrease in temperature during CPR with a rate of 0.12 °C/min and 0.13 °C/min, respectively. This was compared to a rate of 0.03 °C/min, and 0.02 °C/min in the ethanol based surface cooling and control groups, respectively (using ANOVA, p<0.05 between group A and C, A and D, B and C, B and D).

Conclusions:
A cold saline infusion initiated at the start of CPR was determined as the most effective method to achieve intra-CPR TH during SNPeCPR. Further studies will assess the potential neurologic benefit of the combination of SNPeCPR with intra-CPR infusion of cold saline.
Abstract 14642: Cardiac-specific Transgenic Inhibition of NF-kB Attenuates Apoptosis and Remodeling in the Aging Heart
Authors: Ye Sheng , Cheng Guangming , Tang Jifei , Chen Xing , Zhao Lin , Samanta Anweshan , Girgis Magdy , Vincent Robert , Yang Yanjuan , Hauptman Jeryl , Dawn Buddhadeb
Published: April 2024

Introduction:
Aging increases the risk of cardiovascular diseases. Remodeling of the aged heart involves slow yet progressive loss of functional cardiomyocytes, reactive hypertrophy of the remaining cardiomyocytes, and increased fibrosis. NF-κB is one of the major transcription factors that have been linked to cardiovascular disease. Although NF-kB activity increases with aging and aging-related chronic diseases, its role in cardiomyocyte apoptosis and remodeling of the aging heart remains unclear.

Hypothesis:
We hypothesized that myocardial NF-kB signaling would aggravate ventricular remodeling in the aging heart.

Methods:
We used transgenic mice overexpressing a mutant IkBα that prevents NF-kB activation. Cardiac structure and function were assessed by echocardiography and morphometry in young (10-week-old) and aged (86-week-old) IkBα transgenic (Tg) mice and non-transgenic (NTg) littermates. Cardiomyocyte apoptosis and molecular regulators of apoptosis were quantified to gain molecular insights.

Results:
Compared with young NTg mice, aged NTg mice exhibited greater LV mass and LV end-diastolic volume (Fig). This age-related remodeling was significantly blunted in Tg hearts in the absence of myocardial NF-κB activation. The percentage of apoptotic cardiomyocyte nuclei in aged NTg myocardium was significantly higher compared with young NTg and young Tg hearts. Apoptosis was significantly attenuated in aged Tg hearts compared with aged NTg hearts. This decrease in cardiomyocyte apoptosis was corroborated by reduced Bax/Bcl-2 ratio in aged Tg hearts (Fig).

Conclusions:
We conclude that myocardial NF-kB signaling plays a detrimental role during cardiac aging process, and cardiac-specific NF-kB inhibition protects against cardiomyocyte apoptosis and age-associated LV remodeling. These molecular insights may be utilized to develop novel therapeutic strategies for cardiovascular diseases in the aging population.
Abstract 14702: Evaluation of Inflammation in Carotid Disease by New Imaging Modalities: Implications From 18-FDG PET/CT and Microwave Radiometry
Authors: Koutagiar Iosif , Toutouzas Konstantinos , Benetos Georgios , Georgakopoulos Alexandros , Athanasiadis Emmanouil , Trachanellis Sofoklis , Patelis Nikolaos , Filis Konstantinos , Bessias Nikos , Spyrou George , Tousoulis Dimitrios , Anagnostopoulos Constantinos
Published: April 2024

Background and Purpose:
Nowadays, 18F fludeoxyglycose Positron Emmision Tomography/computed tomography (18F-FDG PET/CT) is the leading modality for tracing inflammation within atherosclerotic plaques in vivo, but patients’ exposure to radiation, costs and availability limit its widespread use. We hypothesize that microwave radiometry (MWR), a safe noninvasive method allowing in vivo estimation of atherosclerotic process by measuring temperatures of tissues could be an accurate alternative tool for assessing lesional inflammation. Therefore, the aim of the present study was to investigate the relationship between temperature differences and FDG uptake assessed by MWR and 18F-FDG PET/CT respectively, in patients with significant carotid disease.

Methods:
Consecutive patients, scheduled for carotid endarterectomy due to significant carotid artery (CA) stenosis, underwent 18F-FDG PET/CT and MWR. PET/CT images were acquired 90 min after FDG injection. FDG uptake was measured as maximal standardized uptake value (SUVmax) in consecutive axial slices starting at the bifurcation and extending 2 cm superiorly and 2 cm inferiorly. During MWR evaluation, ΔΤ (maximal temperature across the carotid artery minus minimum) was calculated over the respective carotid segments.

Results:
In total, 44 CAs from 22 patients (18 male) were studied. There was a significant positive correlation between ΔT and SUVmax values in the operated arteries and also between the same parameters in all 44 vessels (R=0.44, p=0.05 and R=0.44, p=0.005, respectively). Operated and non-operated CAs demonstrated similar ΔT and SUVmax values (0.57±0.19 vs 0.59±0.17 °C, p=0.67 and 2.18±0.44 vs 2.28±0.41, p=0.48 respectively). In addition, there was no correlation between the degree of angiographic stenosis and ΔT values (R=0.07, p=0.65) or between lesional SUV measurements and the percentage of luminal stenosis (R=0.10, p=0.55).

Conclusions:
There is a significant correlation between FDG uptake and thermal heterogeneity, indicating that MWR is a promising marker of plaque inflammation. Moreover, there is discrepancy between stenosis severity and inflammation intensity assessed by FDG uptake and MWR, highlighting the diversity of processes involved in CA atherosclerosis.
Abstract 14711: Effect of Release of the First Pediatric Appropriate Use Criteria on Outpatient Transthoracic Echocardiogram Ordering Practice
Authors: Sachdeva Ritu , Kelleman Michael S , McCracken Courtney , Allen Joseph , Benavidez Oscar , Campbell Robert M , Douglas Pamela S , Eidem Benjamin W , Gold Lara , Lopez Leo , Stern Kenan W , Weiner Rory B , Welch Elizabeth , Lai Wyman W
Published: April 2024

Background:
The first pediatric appropriate use criteria (PAUC) were recently published for initial outpatient transthoracic echocardiography (TTE). We sought to determine the effect of release of the PAUC on the appropriateness of TTE ordering patterns of pediatric cardiologists.

Methods:
Data were prospectively collected from patients having initial outpatient TTE ordered prior to (Phase I, 6 mo) and 3 months after release (Phase II, 4 mo) of PAUC. Site-investigators determined the indication of the study and assigned appropriateness rating based on the PAUC document [Appropriate (A), May Be Appropriate (M), or Rarely Appropriate (R)] or "Unclassifiable" (U).

Results:
A total of 4562 TTEs (2655 Phase I, 1907 Phase II) were ordered by 103 physicians at 6 sites. Overall comparison of appropriateness rating for Phase I and II showed no change in the rate for A or M, but a decline in the rate of R and increase in U. Similar results were noted when comparisons were made for physicians that ordered at least 20 TTEs during each phase (N = 30/103, 29%), Table 1. There was no change in any appropriateness rating at 3 sites, a decline in R at 2, an increase in A at 1, and an increase in U at 2 sites. Overall and site-specific comparisons of rate of R TTEs are shown in Fig 1.

Conclusions:
The release of PAUC document had only a small impact on physician ordering behavior for initial TTEs, including a small decrease in R. Overall, these data suggest that more focused interventions are required to fully implement guideline recommendations and improve the appropriate use of pediatric TTE. This information should be helpful in designing educational interventions to reduce the rate of TTEs ordered for R indications.