bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15440: The Incidence and Outcomes of Acute Kidney Injury After TAVR
Authors: Damluji Abdulla , Murman Magdalena , Painter David , Alansari Yahya E , Kabach Mohamad , Novoa Italo , Carrillo Rogerio G , Williams Donald B , de Marchena Eduardo J , Martinez Claudia A , Alfonso Carlos , Moscucci Mauro , Heldman Alan W , Leroux Lionel , Cohen Mauricio G
Published: April 2024

Introduction:
Acute kidney injury (AKI) is a known complication after cardiovascular procedures and is associated with increased all-cause-mortality.

Hypothesis:
We aimed to assess the incidence, predictors, and long-term outcomes of AKI after TAVR.

Methods:
We evaluated inoperable patients with severe aortic stenosis who received TAVR in an academic institution from 04/2008 to 06/2015. AKI was defined according to the consensus report of the Valve Academic Research Consortium. Predictors of AKI were evaluated using multivariable logistic regression modeling.

Results:
Among 457 patients who underwent TAVR, 78 (17%) developed AKI. There were no differences in age, gender, BMI, hypertension, dyslipidemia, smoking status, or medications use among patients with and without AKI. However, patients with AKI were more likely to have diabetes mellitus (DM), chronic kidney disease (CKD) and prior history of stroke than patients without AKI (Figure). Patients with AKI had also lower baseline hemoglobin (AKI: 11 g/dL vs. No AKI: 12, p=0.004) and higher baseline creatinine (1.45 vs. 1.1, p=<0.001). Procedural characteristics that were associated with AKI included: hypotension, IABP/LV assist device use, bleeding, and vascular complications. Patients with AKI had higher all-cause-mortality (14% vs. 2%, p <0.001), higher median hospital length of stay (12 vs. 7 days, p <0.001) and a higher incidence of new dialysis requirement (12% vs. 1%, p <0.001), and dialysis at one month (8% vs. 1%, p =0.001). Multivariate logistsic regression analysis identified DM, CKD, and IABP or LV assist device use as independent predictors of AKI.

Conclusion:
Our results suggest that AKI is relatively common post TAVR and it is associated with increased mortality, length of stay, and dialysis requirement. Patients with underlying CKD and DM who require IABP or LV assist devices for hemodynamic support are at the highest risk of AKI.
Abstract 15476: Genome-wide Transcriptome Study for Myocardial Infarction and Coronary Artery Calcification Using RNA-Seq
Authors: Zhang Xiaoling , Wakabayashi Yoshiyuki , Hwang Shih-Jen , Yang Yanqin , Levy Daniel , Johnson Andrew D , Zhu Jun , O’Donnell Christopher J
Published: April 2024

Introduction:
Coronary artery calcification (CAC) is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). Genome-wide association (GWA) studies have identified common genetic variants associated with MI and CAC. However, the mechanisms underlying MI and CAC remain unclear. We sought to identify gene expression signatures of early MI and high CAC, and further investigate the underlying mechanisms between clinical MI and subclinical atherosclerosis in the Framingham Heart Study (FHS).

Methods:
We conducted a paired-end RNA sequencing on whole blood samples collected from 202 FHS participants (57 with early MI, 74 with high CAC without MI, and 71 control subjects free of elevated CAC levels and MI), with Illumina HiSeq 2000. After filtering non- expressed genes, for each of 12,063 protein-coding genes and 3,704 long intergenic non-coding RNAs (lincRNAs), we applied DESeq2 to identify genes differentially expressed in MI and high CAC, respectively, compared with the control group after adjusting for sex, batch and hidden confounders.

Results:
On average, 150 million paired-end reads were obtained for each sample. Among them, 71% of reads were mapped uniquely to the genome. At the false discovery rate (FDR) <0.1, we found 71 coding genes and 9 lincRNAs differentially expressed between early MI and control. Pathway and gene ontology analysis further indicate that immune response, lipid metabolic process and interferon regulatory factor were enriched in these gene signatures. By contrast, only 3 coding genes are expressed differently between high CAC and controls at FDR<0.1. APOD, encoding a component of high density lipoprotein, was expressed significantly lower in both early MI (FDR=0.007) and in high CAC (FDR=0.01) compared with controls, respectively, identifying a novel candidate for clinical and subclinical MI.

Conclusion:
We identified early MI expression signatures including protein-coding genes and lincRNAs, indicating the power of our extremely deep sequenced data to identify both coding genes and, in particular, lincRNA biomarkers expressed at levels much lower than coding genes. Our results suggest an important role for both protein-coding genes and lincRNAs in the pathogenesis of MI.
Abstract 15509: Circulating Ceramides Predict Fatal and All Incident Major Adverse Cardiovascular Events: A Prospective Analysis of the FINRISK 2002 Cohort
Authors: Havulinna Aki S , Sysi-Aho Marko , Hurme Reini , Laaksonen Reijo , Salomaa Veikko
Published: April 2024

Introduction:
Ceramides are molecular lipids assumed to play a role in apoptosis, inflammation, obesity and insulin resistance. A recent study reported that certain ceramides were associated with fatal outcome among patients with CHD.

Hypothesis:
We hypothesized that ceramides are associated with incident cardiovascular (CVD) outcomes among apparently healthy individuals over and above the traditional risk factors.

Methods:
FINRISK 2002 is a population-based risk factor survey, which recruited 8,798 men and women aged 25-74 years. The participation rate was 65.5%. The cohort was followed up through 31 Dec, 2011, for incident CVD events and through 31 Dec, 2012, for deaths. Our primary outcome was major adverse cardiovascular events (MACE, n= 471). Secondary analyses were carried out for fatal MACE (n=137). Four circulating ceramides (Cer d18:1/16:0, Cer d18:1/18:0, Cer d18:1/24:0, and Cer d18:1/24:1) were determined from frozen samples using mass spectrometry. We used Cox proportional hazard models with age as the time scale to determine associations of the ceramides with incident outcomes. All models were stratified by sex and the full models were adjusted for geographic region, total and HDL-cholesterol, systolic blood pressure, blood pressure medication, BMI, smoking and diabetes. The predictive ability of the ceramides was assessed by estimating the 10-year absolute risk of MACE and comparing the full models with and without ceramides. The predictions were done using 10-fold cross-validated Weibull proportional hazard models.

Results:
When considered one by one, three out of the four ceramides were significantly associated with the risk of incident MACE in the fully adjusted Cox models. Ceramide score, formed as a linear combination of the four ceramides had a hazard ratio (HR) of 1.75 (p=0.005) in the full model. C-statistics did not change significantly but the net reclassification improvement among persons with intermediate risk was significant 6.2% (2.6 - 9.7%). The association of the ceramide score with fatal MACE was even stronger than with all MACE: HR=2.31 (p=0.02).

Conclusions:
These results show the potential of lipidomics profiling in producing new insights in the pathogenesis of CVD and suggesting new therapeutic targets.
Abstract 15520: The Association of a Genetic Risk Score With Presence of Polyvascular Disease
Authors: Ye Zi , Austin Erin , Arruda-Olson Adelaide M , Kullo Iftikhar J
Published: April 2024

Background:
Atherosclerotic cardiovascular disease (ASCVD) often affects > 1 arterial location (polyvascular disease, PVD). The risk of adverse outcomes increases with the number of arterial territories involved. The genetic susceptibility to PVD is unknown.

Hypothesis:
We hypothesized that a genetic risk score representing cumulative effects of susceptibility variants to ASCVD is associated with presence of PVD.

Methods:
We searched genome-wide association study (GWAS) catalog to identify genetic variants associated with coronary heart disease (CHD), ischemic stroke, peripheral arterial disease (PAD) or abdominal aortic aneurysm (AAA). No variants were reported to be associated with PVD in ≥ 3 arterial territories at GWAS significance. 10 loci were associated with PVD in 2 arterial territories. We calculated a multi-locus GRS using 10 lead single nuclear polymorphisms (SNP) from these distinct loci (1 per each loci) in 7486 participants in Mayo Vascular Disease Biorepository (age 68±10 years, 61% men, 31% with CHD; 27% carotid artery stenosis; 39% PAD; 14% AAA; 38% without any of these vascular diseases).

Results:
Of all participants 34% had PVD (2%, 10% and 22% with exact 4, 3 and 2 arterial territories involved respectively). A higher GRS was associated with greater number of arterial territories involved (P for trend of ANOVA <0.001). Patients with PVD in ≥ 3 arterial locations had higher GRS compared to those with 2 arterial locations involved after adjustment for age, sex and cardiovascular risk factors (P =0.008). One unit increase in GRS was associated with 9% higher likelihood for each additional arterial territory involved after adjustment for all covariates (odds ratio from ordinal regression model= 1.09, P <0.001). The result remained significant after further adjustment for combinations of AAA, CHD, carotid arterial stenosis and PAD (all P ≤ 0.01). 5 Of the 10 SNPs were each associated with presence of PVD after adjustment for all covariates (all P <0.01). None of them remained significant after further adjustment for combinations of PVD in different arterial territories (all P ≥ 0.4).

Conclusions:
A GRS derived from 10 SNPs of ASCVD is associated with PVD,suggesting genetic contribution to the dimension of PVD that may lead to adverse outcome.
Abstract 15581: Nocturnal Blood Pressure is Associated With Localized Retinal Nerve Fiber Layer Defects on Optical Coherence Tomography
Authors: Yu Hee Tae , Oh Jaewon , Shin Joo Youn , Byeon Suk Ho , Park Sungha , Lee Sang-Hak , Kang Seok-Min , Choi Donghoon
Published: April 2024

Introduction:
Retinal damages have been suggested a surrogate marker of end-organ damage and prognostic marker in hypertensive patients. Recent study reported that localized retinal nerve fiber layer defects (RNFLDs) assessed by noninvasive optical coherence tomography (OCT) was related to the degree of hypertension severity and cerebrovascular disease.

Purpose:
We hypothesize that RNFLDs are related to the parameters of 24 hour ambulatory blood pressure monitoring (ABPM).

Methods:
RNFLDs were assessed by retinal OCT in 562 consecutive subjects enrolled in Cardiovascular and Metabolic Disease Etiology Research Center - HIgh Risk Cohort (CMERC-HI, NCT02003781). We excluded the patients with glaucoma, which known to be related to RNFLD independently of cardiovascular risk factors.

Results:
RNFLD was found in 129 (23.0%) patients. In patients with RNFLD, there were higher proportion of men, higher prevalence of hypertension, higher glucose levels and lower HDL-cholesterol levels. The RNFLD patients had higher 24 hour mean systolic and diastolic blood pressure (SBP/DBP, 133±16/80±9 vs. 129±13/78±8, p=0.022/p=0.015, respectively) and nocturnal mean SBP/DBP (124±19/74±9 vs. 120±15/72±9, p=0.013/p=0.010, respectively) compared to those without RNFLD. Multivariate stepwise linear regression analysis revealed that RNFLD was independently associated with nocturnal mean SBP after controlling for age, gender, diabetes mellitus, smoking, body mass index, brachial systolic blood pressure, heart rate, estimated glomerular filtration rate, heart to femoral pulse wave velocity (β=0.093, p=0.036, R2=0.263).

Conclusion:
We reported that RNFLD on OCT was related to nocturnal blood pressure in 24 hour ABPM for the first time. Further studies which validate RNFLD as a cardiovascular surrogate and risk marker should be warranted.
Abstract 15729: Copper Transporter ATP7A Limits Vascular Inflammation and Aortic Aneurysm Development
Authors: Varadarajan Sudhahar , Das Archita , Youn Seock-Won , Kohno Takashi , Surenkhuu Bayasgalan , Ushio-Fukai Masuko , Fukai Tohru
Published: April 2024

Vascular inflammation and its-induced endothelial cell (EC) barrier dysfunction contribute to aortic aneurysm (AA) development. However, critical regulators of AA are poorly understood. Copper (Cu), an essential micronutrient, at excess level is shown to promote inflammatory diseases including AA with unknown mechanism. Cu transporting ATPase (ATP7A) functions to deliver Cu to the secretory extracellular matrix enzyme lysyl oxidase (LOX) via Cu chaperone Atox1, or exclude Cu. Here we show that ATP7A is a key regulator of vascular inflammation and AA formation using ATP7A mutant (ATP7Amut) mice with reduced Cu transport function. ATP7Amut/ApoE-/- mice fed with high fat diet (HFD) induced a robust AA formation (70%) with enhanced atherosclerotic lesion (3.9 fold), which was associated with increased macrophage recruitment and matrix metalloproteinase 2 & 9 activity vs. ApoE-/-/HFD or Atox1-/-/ApoE-/-/HFD mice. Of note, both ATP7Amut and Atox1-/- mice showed similar extent of reduced LOX activity (54%) indicating that decrease in LOX activity was not sufficient to develop AA. However, EC permeability was markedly increased only in ATP7Amut/ApoE-/- mice. Mechanistically, ATP7A depletion or proinflammatory cytokine TNFα in HUVECs increased EC permeability (132%) and leukocyte transendothelial migration (TEM) (p<0.05) in a Cu dependent manner. To determine the ATP7A dependent microRNAs (miRs), we performed miRs array and found that miR125b is highly upregulated (9 fold) miRs in ATP7A depleted ECs. Of note, miR125b is shown to suppress VE-Cadherin (VE-Cad) expression by inhibiting translation of 3’UTR of VE-cad mRNA. Consistent with this, ATP7A depletion upregulated miR125b and downregulated VE-Cad, thereby increasing EC permeability, which were rescued by anti-miR125b. Furthermore, ATP7A knockdown caused Rac1-mediated actin disassembly in Cu dependent manner, which also contributed to EC barrier dysfunction. In summary, endothelial ATP7A protects against AA formation by preventing inflammation-induced EC permeability and excess inflammatory recruitment via regulating actin reorganization, VE-Cad expression, and LOX activity in a Cu dependent manner. Thus, ATP7A is a potential therapeutic target for inflammatory vascular disease.
Abstract 15736: The Effect Of Genotype on the Clinical Presentation and Outcomes in Newly Diagnosed Patients With ARVC
Authors: Szepietowska Barbara , Towbin Jeffrey A , Marcus Frank , Mestroni Luisa , Polonsky Bronislava , Zareba Wojciech
Published: April 2024

Objective:
The aim of the study was to compare clinical presentation of newly diagnosed patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) by presence of genes mutations, and the effect of known genotype on the risk of ventricular tachyarrhythmias (VT/VF) or death.

Methods:
There were 109 newly identified probands diagnosed with ARVC according to the 2010 Task Force criteria for ARVC and tested for the following genes: (numbers of specific mutations identified are provided in parentheses): Plakophilin 2 (n=29), Plakoglobin (n=8), Desmocollin (n=1), Desmocollin 2 (n=1), Desmoglein (n=3), Desmoglein 2 (n=2), Desmoplakin (n=8).

Results:
There were 32 (29.4%) genotype positive patients for mutation in just one of the tested genes and 9 (8.3%) patients had 2 or 3 mutation concomitantly, in 6 of them the co-present mutation was Plakophilin 2. The remaining 68 (62%) patients were genotype negative for the above genes. Gene-positive patients for single and for multiple mutations patients and patients with unknown yet gene mutations did not differ significantly in clinical presentation including: age at clinical presentation, age at the first VT/VF, family history of ARVD, diagnostic criteria points, arrhythmic events (VT/VF) prior to enrolment and ICD implantation, ECG presentation, EP testing, ECHO or MRI parameters. Figure below shows the risk of VT/VF/ Death in three groups of patients: single mutations vs. multiple mutations vs. unknown gene group.

Conclusion:
ARVC patients with unknown genes show similar clinical, ECG, and MRI presentation and similar outcome to patients with single or multiple mutations. Future studies are needed to uncover unknown genes underlying ARVC.
Abstract 11158: Trends in Heart Failure Hospitalizations Using Data From National Hospital Discharge Survey
Authors: Munir Muhammad Bilal , Sharbaugh Michael S , Thoma Floyd W , Nisar Muhammad Umer , Kamran Amir S , Althouse Andrew D , Saba Samir
Published: April 2024

Aims:
Heart failure (HF) is a common cause of hospital admission. However, relatively little data have described temporal trends in HF hospitalization. We present data on the number of HF admissions, length of stay and inpatient mortality from 1996-2010.

Methods:
Data were obtained from the National Hospital Discharge Survey (NHDS), a national probability sample survey of discharges conducted annually by the National Center for Health Statistics. Because of the survey design, sampling weights are applied to the raw NHDS data to produce national estimates. Hospitalizations with a primary diagnosis of HF were identified using ICD-9 codes. Weighted least squares regression was used to test for linear trends in the number of HF admissions, length of stay, and inpatient mortality.

Results:
The raw data contained 130,079 HF hospitalizations, translating to an estimated 16.7 million hospitalizations from 1996-2010 after application of sample weights. The total number of hospitalizations increased over time (p=0.05; see Figure); however, mean length of stay per hospitalization declined (p<0.001; see Figure). Inpatient mortality rate has also declined (p<0.001; see Figure).

Conclusion:
In a nationally representative sample of HF hospitalizations, mean length of stay and inpatient mortality rates have been declining over the past two decades. These trends reflect improvement in HF management over time, and have important implications in the cost of managing HF patients.
Abstract 11169: Whole Exome Sequencing in Subjects With Mendelian Form of Primary Severe Hypertriglyceridemia
Authors: Tada Hayato , Nomura Akihiro , Kawashiri Masa-aki , Nohara Atsushi , Inazu Akihiro , Mabuchi Hiroshi , Kathiresan Sekar , Yamagishi Masakazu
Published: April 2024

Background:
Few data exist regarding clinical application of whole exome sequencing (WES) for the molecular diagnosis of the subjects with Mendelian form of primary severe hypertriglyceridemia (HTG).

Methods:
WES was performed on 28 individuals exhibiting severe HTG (≥ 1,000 mg/dl) without any transient causes (15 men, mean age 42 ± 20 yr, median triglyceride 1,756 mg/dl [interquartile range 1,288-2,443]) followed by recessive and dominant inheritance modeling in known monogenic HTG genes and disease-network candidate analysis gene ranking to identify a causative mutation(s), including novel underlying genetic mechanism for severe HTG.

Results:
Using our schema, we identified possible causative mutation(s) in 14 individuals (50%). Among them, we identified 2 individuals with lipoprotein lipase (LPL) deficiency with double mutations in LPL gene, and 2 individuals with a heterozygous mutation carrier in LPL gene. Moreover, we identified one individual harboring a double mutations in LPL gene and APOA5 gene. Also we identified one individual with a heterozygous mutation in lipase maturation factor 1 (LMF1) gene, which is rarer form of familial hyperchylomicronemia, and 2 individuals with type 3 hyperlipidemia harboring mutations in APOE gene, including novel ones. Interestingly, we also identified 6 other individuals harboring a deleterious mutation in cyclic AMP-responsive element-binding protein 3-like protein 3 (CREB3L3), MLX Interacting Protein-Like (MLXIPL), SLC25A40 genes, glucokinase regulatory protein (GCKR), possibly associated with this extreme phenotype.

Conclusion:
We identified potential causative mutations in 14 among 28 individuals (50%) with severe HTG within the coding region of the genes known to cause rare Mendelian dyslipidemias. Clinical WES is now feasible where molecular diagnoses could be made in such extreme cases, which could potentially provide appropriate therapies.
Abstract 11174: Diagnosis and Prognosis Using the V-index in Patients With Symptoms Suggestive of Acute Myocardial Infarction
Authors: Abächerli Roger , Twerenbold Raphael , Boeddinghaus Jasper , Nestelberger Thomas , Sassi Roberto , Minardi Luca , Osswald Stefan , Mueller Christian
Published: April 2024

Introduction:
The V-index is an ECG marker quantifying the spatial heterogeneity of ventricular repolarization. We prospectively investigated the diagnostic and prognostic value of the V-index in patients with symptoms suggestive of acute myocardial infarction (AMI).

Methods:
We enrolled 582 patients presenting with suspected AMI to the emergency department (ED) in a prospective observational study. Twelve lead ECG’s of five minutes were recorded at presentation to the ED. The V-index was calculated in a blinded fashion. Final diagnosis was adjudicated by two independent cardiologists. Patients were followed for the endpoint of all-cause mortality.

Results:
AMI was the final diagnosis in 16% of patients. Values for the V-index at presentation were higher in patients with AMI compared to other causes of chest pain (23ms (IQR 18-28) vs. 18ms (IQR 15-24), p<0.001). The diagnostic accuracy of the V-index at presentation for the diagnosis of AMI as quantified by the area under the receiver operating characteristic curve (AUC) was 0.64 (95% CI 0.57-0.71). The use of the V-index in addition to conventional ECG criteria improved the sensitivity of the ECG for MAI from 41% to 85% (p<0.001). Median V-index levels in deceased patients were significantly higher as compared to survivors (28ms (IQR 22-37) vs. 19ms (IQR 15-24), p<0.001). Cumulative 24-month mortality rates were 99.5%, 97.2% and 90.4% according to tertiles of the V-index (p<0.001). In multivariable Cox proportional hazard analysis, the V-index significantly predicted mortality independently of age and high-sensitive cardiac Troponin T (hs cTnT).

Conclusion:
The V-index, an ECG marker quantifying the spatial heterogeneity of ventricular repolarization, significantly improves the sensitivity of the ECG for the diagnosis of AMI and predicts mortality in patients with suspected AMI independently of age and hs-cTnT.
Abstract 11177: No ST-Segment Elevation Resolution in Lead aVR Strongly Predicts In-hospital Adverse Outcomes in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome
Authors: Kosuge Masami , Ebina Toshiaki , Hibi Kiyoshi , Iwahashi Noriaki , Maejima Nobuhiko , Matsuzawa Yasushi , Kimura Kazuo
Published: April 2024

Introduction:
ST-segment elevation in lead aVR (ST↑aVR) on admission ECG is considered a useful predictor of left main/3-vessel disease (LM/3VD) and poor outcomes in patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS). However, the prognostic value of the change in ST↑aVR after admission remains unclear.

Hypothesis:
ST-segment analysis of lead aVR after admission may facilitate risk stratification in NSTE-ACS.

Methods:
We studied 706 patients with NSTE-ACS undergoing coronary angiography during hospitalization. ECGs were recorded on admission and 6 h after admission. ST↑aVR ≥0.5 mm was considered significant. A reduction of >50% in ST↑aVR between the value on admission and that 6 h later was defined as ST resolution. Patients were classified into the 3 groups according to ECG findings: G-A, no ST↑aVR on admission (n=526); G-B, ST↑aVR on admission with ST resolution (n=114); and G-C, ST↑aVR on admission without ST resolution (n=66). Troponin T (TnT), estimated glomerular filtration rate (eGFR), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP), and summed ST-segment depression (ST↓) were measured on admission.

Results:
There were no significant differences in sex or coronary risk factors except for diabetes mellitus in the 3 groups. In G-A, G-B, G-C, age was 66±11, 69±11, and 70±11 years; the rates of diabetes mellitus were 29%, 43%, and 55%; Killip ≥2 was 4%, 18%, and 27%; and positive TnT was 27%, 42%, and 53%; the levels of eGFR were 67±24, 61±27, and 54±28 ml/min/1.73 m
2
; BNP was 148±274, 358±418, and 617±545 pg/ml; hsCRP was 0.414±2.008, 0.655±1.551, and 1.125±2.058 mg/dl; summed ST↓ was 2±2, 7±4, and 11±7 mm; the rates of LM/3VD were 6%, 38%, and 86%; and in-hospital adverse events (death, [re]infarction, or urgent revascularization) were 6%, 17%, and 35%, respectively (all p<0.01). Multivariate analysis showed that as compared with no ST↑aVR , hazard ratios (95% CI) for in-hospital adverse events associated with ST↑aVR with ST resolution and that without ST resolution were 1.60 (0.68-4.38; p=0.25), and 6.11 (2.07-14.9; p<0.001), respectively.

Conclusions:
No resolution of ST↑aVR, ie., persistent ST↑aVR 6 h after admission, strongly predicts in-hospital adverse outcomes in patients with NSTE-ACS.
Abstract 11245: Normal Findings in Late Gestation Fetal Echocardiography
Authors: Tague Lauren , Donofrio Mary T , Fulgium Amanda , McCarter Robert , Limperopoulos Catherine , Schidlow David
Published: April 2024

Introduction:
Fetal echocardiography (FE) provides detailed information about cardiac structure and function in-utero. Limited information is available regarding normal findings late in pregnancy. We sought to identify and describe common FE findings in late gestation.

Methods:
Fetuses with structurally normal hearts at mid-gestation were identified within a subset of pregnant women in a prospective study. Atrioventricular (AV) valves, right and left atrium (RA/LA), aortic isthmus (AoI) and ductal arch (DA) diameters and flow abnormalities, septum primum aneurysm (SPA), and presence/grade of tricuspid regurgitation (TR) were assessed. Linear and logistic regression analyses were used to characterize change in quantitative and qualitative FE parameters.

Results:
40 fetuses were studied. Each had a FE completed before and after 34 weeks gestation. Studies were compared. RA/LA and tricuspid/mitral valve (TV/MV) ratios increased with GA (p<0.001). Increased AoI and DA diastolic flow, and trivial/mild TR were more frequently identified after 34 weeks gestation. Increased AoI diastolic flow, DA narrowing, DA diastolic flow, TR, and SPA increased linearly with GA (p<0.001).

Conclusion:
Mild RA/LA and AV valve disproportion, trivial/mild TR, isolated AoI diastolic flow, mild DA narrowing, and SPA are frequently seen after 34 weeks GA. This suggests these FE findings in isolation are likely normal as physiologic changes occur in late gestation. Figure 1: RA/LA disproportion and AV disproportion increase with gestational age. P<0.001.
Abstract 11250: Long-term Outcomes for Patients With Atrial fibrillation and a Rapid Ventricular Response: A Comparison of Those With Reduced Versus Preserved Ejection Fraction at Initial Hospitalization
Authors: Benjamin Mina M , Chaddha Ashish , Sampene Emmanuel , Field Michael E , Rahko Peter
Published: April 2024

Background:
Patients presenting with new onset atrial fibrillation with rapid ventricular response (AFRVR) may present with a reduced left ventricular ejection fraction (LVEF). We hypothesized that these patients have worse outcomes than patients presenting with preserved LVEF.

Methods:
Retrospective cohort study of 385 consecutive patients with new onset AFRVR, presenting between 01/2006 and 08/2014. Patients with a history of coronary artery disease or known cardiomyopathy were excluded. Patients were divided into those with reduced EF (REF) (LVEF ≤ 55%, n=147), and those with a preserved EF (PEF) (LVEF> 55%, n=238). Echocardiographic parameters, stroke rates, all-cause, and cardiovascular mortality were compared at baseline and a minimum of 1 year follow-up.

Results:
Mean age was 68 +/- 1.1 in REF versus 60 +/- 7.4 in PEF (p=0.39). There were no significant differences in baseline comorbidities. Mean LVEF was 47.7+/- 0.8% in REF vs 65.5 +/- 0.3% in PEF. The average duration of follow-up was 2.8 years. REF patients had higher all-cause mortality (32.7% REF vs 20.6% PEF, OR 2.17, p= 0.008) but similar cardiovascular mortality (15% REF vs 15.1% PEF, p=0.97). REF patients had higher rates of subsequent clinic or ER visits for AFRVR (32% REF vs 22.7% PEF, p=0.044). The incidence of stroke was similar between both groups (17% REF vs 18.9% PEF, p=0.639). Of REF patients, 29.7% had subsequent EF recovery; this subset had similar outcomes compared to PEF patients. Baseline left ventricular end diastolic diameter (LVEDD) predicted all-cause mortality (OR 1.14, p=0.003) in REF group. None of the echocardiographic parameters predicted EF recovery.

Conclusion:
In this cohort of patients with new AFRVR, REF was associated with higher long-term all-cause mortality and AFRVR recurrence. Those with subsequent LVEF recovery after medical therapy appear to have outcomes similar to those with PEF.
Abstract 11301: Lower Systemic Arterial Compliance is Associated With Increased Cardiovascular Morbidity and Mortality in Aortic Valve Stenosis
Authors: Bahlmann Edda , Cramariuc Dana , Lonnebakken Mai Tone , Gohlke-Baerwolf Christa , Pedersen Terje , Nienaber Christoph A , Chambers John B , Kuck Karl Heinz , Gerdts Eva
Published: April 2024

Introduction:
Systemic arterial compliance (SAC) significantly influences cardiovascular morbidity and mortality in hypertension, but this has not been assessed in a prospective study in aortic stenosis (AS).

Hypothesis:
Lower SAC is associated with reduced outcome in AS.

Methods:
Data from 1471 patients (38% women) with initially asymptomatic mild-moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study was used. Median follow-up was 4.3 years. SAC was assessed as the ratio of stroke volume index to central pulse pressure.

Results:
In multivariable linear regression analysis, lower SAC at baseline was associated with older age, hypertension, obesity, presence of a small aortic root and more severe AS (all p<0.001). In Cox regression analysis, lower SAC (per 1 ml/m
2
/mmHg) was associated with higher hazard rates for major cardiovascular events, aortic valve events, ischemic cardiovascular events and total mortality (all p<0.05), also after adjusting for hypertension, left ventricular mass, AS severity, presence of a small aortic root, randomized study treatment and aortic valve replacement (Table).

Conclusion:
In AS patients without known cardiovascular disease, but a high prevalence of hypertension, lower SAC is associated with higher morbidity and mortality independent of other well-known prognosticators. Table. The association of lower SAC with cardiovascular events in asymptomatic AS in multivariable Cox analyses.
Abstract 11417: Elevated Serum Osteoprotegerin is Associated With Increased Left Ventricular Mass Index and Left Ventricular Diastolic Stiffness in African Americans: Insights From the Genetic Epidemiology Network of Arteriopathy (GENOA) Study
Authors: Kamimura Daisuke , Suzuki Takeki , Furniss Anna L , Griswold Michael E , Lindsey Merry L , Winniford Michael D , Butler Kenneth R , Mosley Thomas H , Hall Michael E
Published: April 2024

Background:
Osteoprotegerin (OPG) associates with a poor prognosis in patients that have already developed heart failure with preserved ejection fraction (HFpEF). OPG also associates with fibrosis and collagen cross-linking which increase diastolic stiffness in the left ventricle (LV). Little is known about the relationship of OPG and LV structure and function in African Americans who are disproportionately affected by HFpEF. We hypothesized that OPG may serve as an early indicator of developing LV hypertrophy and stiffening which are prominent precursors to HFpEF.

Methods and Results:
Our analysis included 1172 participants with preserved LV ejection fraction (EF >50%) from the African American (Jackson) cohort of the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.9 years, 72% female). LV diastolic stiffness was assessed by echocardiography using the recently developed diastolic wall strain (DWS) indicator calculated as (LV posterior wall thickness at end-systole - LV posterior wall thickness at end-diastole) / LV posterior wall thickness at end-systole. Associations between serum OPG levels and indices of LV structure and function were evaluated using a generalized linear mixed models (GLMM) accounting for clustering in siblings, and adjusted for possible confounders including age, gender, past history of hypertension and diabetes, current smoking status and estimated glomerular filtration rate (eGFR). OPG levels correlated with age, female sex, presence of hypertension and diabetes, lower eGFR, and higher N-terminal prohormone brain natriuretic peptide levels (p <0.05 for all). Thus, higher OPG levels were associated with characteristics common in patients with HFpEF. Multivariable linear regression analysis revealed that after adjustment for covariates, higher OPG levels were associated with greater LV mass index and increased LV diastolic stiffness (p <0.05, for all).

Conclusions:
Higher OPG levels associated with characteristics common in patients with HFpEF in African Americans. The serum OPG levels also significantly associated with known precursors to HFpEF, indicating a potential pathophysiologic role for OPG in the development of HFpEF in African Americans.
Abstract 11420: Racial Differences in Heart Failure Presentation and Outcome: A Get-With-The-Guidelines Heart Failure Study
Authors: Eno Eben , Nathan Karim , Mithani Ali , Daneshvar Mitra , Ortman Matthew , Andriulli John , Russo Andrea M
Published: April 2024

Background:
Millions of Americans are living with heart failure (HF), and minorities represent a large proportion of these patients. Racial differences in outcomes of patients with HF have been previously described. Examining racial differences in presentation and factors precipitating admission with HF in minorities may help to reduce gaps in care and improve outcomes.

Methods:
We examined 3763 all-cause admissions for HF at our center (2005-2012) using the GWTG-HF study. Minorities represented 33% of the overall cohort (1216 blacks and 39 other races). Baseline characteristics and outcomes were compared between minorities and Caucasians using independent T Test, Pearson Chi Square and Fisher Exact Test during index admissions.

Results:
Racial differences in baseline characteristics and comorbidities were identified. (Table) Compared to Caucasians, minorities were younger, had a higher BMI, and were more likely to have nonischemic cardiomyopathy, HTN, diabetes, and renal insufficiency. Minorities were also more likely to be uninsured and were less likely to have CAD, prior MI and atrial fibrillation. Minorities had a 1.3 times greater odds than Caucasians to be readmitted (95% CI 1.1 -1.5). When examining factors contributing to HF admission, minorities were more likely to have medical (34% vs. 17%) or dietary (63% vs. 51%) noncompliance, worsening renal failure (28% vs. 21%), or worsening hypertension (46% vs. 28%) than Caucasians. (p <0.001 for all).

Conclusion:
Minorities with HF demonstrated significant differences in comorbidities, insurance status, and triggers for HF exacerbations than Caucasians, leading to a greater risk for re-hospitalization. A focus on racial differences in factors precipitating HF exacerbations or potential differences related to access to care that vary by race may provide a more targeted approach to improving outcomes and reducing readmissions, helping to reduce racial gaps.
Abstract 11480: Obesity and Long Term Outcomes After ST-elevation Myocardial Infarction in the Elderly: Does the Paradox Extend to Extreme Obesity? : Results From the National Cardiovascular Data Registry
Authors: Neeland Ian J , Simon DaJuanicia N , Wang Tracy Y , Diercks Deborah B , Roe Matthew T , Alexander Karen P , Das Sandeep R , de Lemos James A
Published: April 2024

Introduction:
An obesity paradox exists in non-STEMI in which patients with mild obesity have lower mortality than normal weight patients. It is not known if this paradox exists among older patients with STEMI and among individuals with extreme obesity over the long term.

Methods:
Patients ≥65 years of age with STEMI from the NCDR ACTION Registry-GWTG who survived to hospital discharge were linked to Medicare claims data. Patients were stratified by body mass index (BMI, kg/m
2
) into normal weight (18.5-24.9), overweight (25-29.9), class I obese (30-34.9), class II obese (35-39.9), and class III (extreme) obese categories (≥40). Multivariable Cox proportional hazards models were used to evaluate the association between BMI category and all-cause mortality for 3 years after hospital discharge. Models were adjusted for clinical and socioeconomic (SES) characteristics and in-hospital outcomes. Differences in number of days alive and out of hospital (DAOH) were also assessed.

Results:
Of 19,499 patients included in the analysis, 70% were overweight or obese. Normal weight patients (30%) were more likely to be older and smoke and extremely obese patients (3%) more likely to be younger, female, and black, with lower SES and more comorbidity (P≤0.001). After multivariable adjustment, a U-shaped association was observed between BMI and long term mortality. Patients with mild (class I) obesity were at lowest risk, while normal weight or extremely obese patients had higher all-cause mortality (
Figure
). Normal weight and extremely obese individuals also had lower DAOH at 3 years compared with mildly obese (median 894 vs. 950 days, respectively, P<0.05).

Conclusions:
The obesity paradox persists in older STEMI patients over long term with regards to death and readmission but is not seen with extreme obesity. Normal weight and extreme obesity are associated with consistently worse outcomes highlighting a need for aggressive treatment paradigms for these populations after STEMI.
Abstract 11550: Underutilization of Anticoagulation for Stroke Prevention among 5,000 Consecutive Hospitalized Atrial Fibrillation Patients
Authors: Piazza Gregory , Hurwitz Shelley , Harrigan Lindsay , Jenkins Kathryn , Hohlfelder Benjamin , Fanikos John , Samuel Goldhaber Z
Published: April 2024

Introduction:
Failure to prevent stroke in patients with atrial fibrillation (AF) has become an increasingly important patient safety concern.

Hypothesis:
We hypothesized that anticoagulation would be underutilized in hospitalized patients with AF at our tertiary care referral center.

Methods:
5,000 consecutive patients hospitalized at Brigham and Women’s Hospital between May 2008 and September 2014 with nonvalvular AF were identified and evaluated.

Results:
All-cause mortality at 90 days was 5.4%. The frequencies of death between hospital discharge and Day 90 were higher in patients who were not prescribed anticoagulation at discharge (7.1% vs. 2.8%, p < 0.0001). Anticoagulation prescription at discharge was associated with a 60% reduction in death between discharge and Day 90, after adjustment for confounding factors. Anticoagulation was prescribed at discharge to 61.6% of patients with a CHA
2
DS
2
-VASc score of at least 1 (Figure). The most frequent reasons for omitting anticoagulation were bleeding risk and peri-operative state.

Conclusions:
Prescription of anticoagulation was lower than expected in patients with AF during hospitalization and at discharge. Patients with AF who were not prescribed anticoagulation at discharge had an increased risk of death at 90 days.
Abstract 11571: Beneficial Effect of Early Infusion of Landiolol; A Very Short Acting Beta1 Adrenergic Receptor Blocker, on Reperfusion Status in Acute Myocardial Infarction
Authors: Kiyokuni Masayoshi , Kino Tabito , Kagimoto Minako , Yamada Nao , Iwata Kiwamu , Nakayama Naoki , Takano Keiko , Komura Naohiro , Nitta Manabu , Sugano Teruyasu , Endo Tsutomu , Ishigami Tomoaki , Ishikawa Toshiyuki , Kimura Kazuo
Published: April 2024

Introduction:
Landiolol is the beta-1 selective receptor blocker and its half-life elimination is 4 minutes. The safety and efficacy of landiolol started before coronary reperfusion in patients with ST-segment elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI) remains unclear. We assessed the hypothesis that very early use of landiolol promotes optimal reperfusion without increasing adverse events for those patients.

Methods:
We conducted a prospective, single-group trial of landiolol during the pPCI for a STEMI. Landiolol was started intravenously just before the pPCI with 3 μg/kg/min. The reperfusion status and clinical outcomes in 55 treated patients were compared with those in 60 historical control patients treated without landiolol. The optimal reperfusion was assessed by an ST-segment resolution (STR), coronary flow, myocardial brush grade (MBG) and peak creatine kinase (CK) after reperfusion.

Result:
Time from admission to starting landiolol was 35±23min in landiolol group. Age, sex, coronary risk factors, culprit lesion, SYNTAX score and reperfusion time did not differ between landiolol group and control group (all NS). Those in the landiolol group achieved a higher rate of an STR (64% vs. 42%,
p
=0.023) and MBG 2/3 (64% vs. 45%,
p
=0.045), whereas coronary flow and peak CK were comparable between the two groups. A multivariate analysis showed that landiolol use was an independent predictor of an STR (OR 2.99, 95% CI 1.25-7.16,
p
=0.014). The incidence of non-sustained ventricular tachycardia (27% vs. 50%,
p
=0.014), hypotension (15% vs. 32%,
p
=0.046) and progression to Killip class grade III or IV (0% vs. 10%,
p
=0.028) during admission were lower in the landiolol group. Within 12 months after the admission, the rate of worsening heart failure (0vs7%, p=0.07) tended to be lower in landiolol group. Left ventricular ejection fraction and end-diastolic volume index in 12 months after the admission did not differ between the two groups (landiolol group vs control group: 59±11%vs56±15%, p=0.23; 60±14vs63±30ml/m
2
, p=0.62).

Conclusion:
In patients with STEMI, intra-procedural landiolol in pPCI may attenuate myocardial reperfusion injury and reduce adverse events.
Abstract 11614: The Clinical Significance and Novel Mechanism of Reactive Oxygen Species in Heart Failure With Preserved Left Ventricular Ejection Fraction
Authors: Yamamoto Eiichiro , Hirata Yoshihiro , Tokitsu Takanori , Oike Fumi , Fujisue Koichiro , Yamamuro Megumi , Kaikita Koichi , Hokimoto Seiji
Published: April 2024

Introduction:
By performing basic and clinical researches, we investigated the clinical significance of reactive oxygen species (ROS) biomarker and the mechanism of ROS production in heart failure with preserved left ventricular ejection fraction (HFpEF).

Methods and Results:
(1) We measured derivatives of reactive oxidative metabolites (DROM), new biomarker of ROS, in 287 HFpEF patients, and followed them. DROM was significantly higher in HFpEF patients compared to risk factor matched non-HF patients (p<0.001), and was associated with the severity of HF (p<0.001). Kaplan-Meier analysis demonstrated higher probability of cardiovascular events in high-DROM than low-DROM group (p=0.01). Multivariate Cox hazard analysis identified ln-DROM as independent predictor for cardiovascular events (p=0.04). (2) We examined the association of ROS with galectin-3, a predictor of cardiovascular events in HFpEF, by using angiotensin II (AII) receptor blocker (ARB) and galectin-3-inhibitor (Gal3-i) administrated Dahl salt-sensitive rats (DS rats), useful model of HFpEF. Increased left ventricular (LV) galectin-3 protein expressions by Western blotting in HFpEF DS rats were inhibited by ARB, indicating AII-induced galectin-3 expression in HFpEF. Furthermore, Gal3-i significantly reversed LV hypertrophy in DS rats suffered HFpEF (p=0.02), accompanied by the tendency of reduction in collagen-related mRNA gene expression (collagen-I, -III and MMP-2) by real-time RT-PCR. Serum DROM and LV mRNA gene expressions of subunits of ROS generative NADPH oxidase (p22
phox
and NOX-2) were increased in HFpEF rats, and Gal3-i tended to downregulate them. These indicated AII induced galectin-3 is involved in LV fibrosis via ROS. (3) Galectin-3 at coronary sinus was higher than at aortic root in HFpEF patients, but not different in non-HF, indicating galectin-3 production in coronary circulation in HFpEF. Moreover, Kaplan-Meier analysis demonstrated higher probability of cardiovascular events in plasma high galectin-3 than in low galectin-3 group in HFpEF patients (p<0.05), indicating clinical significance of galectin-3.

Conclusions:
These studies demonstrated clinical significance and novel mechanism of ROS in HFpEF.
Abstract 11780: Temporal Trends, Racial and Gender Differences in the Use of Oral Anticoagulation in Medicare Patients With Newly Diagnosed Atrial Fibrillation
Authors: Kabra Rajesh , Vaughan Sarrazin Mary
Published: April 2024

Introduction:
The novel oral anticoagulants (NOAC’s) have provided convenient anticoagulation alternatives to warfarin for stroke prevention in atrial fibrillation (AF) patients.

Hypothesis:
We sought to study the temporal trends and racial/gender differences in the use of anticoagulants in AF patients from 2011 to 2013 in Medicare patients with newly diagnosed AF.

Methods:
Medicare claims from January 2010 to December 2013 were used to identify patients ≥66 years of age with newly diagnosed AF during 2011-2013, with no documented AF or anticoagulant use in the prior year. Race was identified from the Beneficiary Summary File. Data regarding initiation of oral anticoagulation within 90 days of AF diagnosis as well as type of anticoagulant were collected. We compared oral anticoagulant use for each year by race and sex.

Results:
Of the 755,079 patients with newly diagnosed AF, 85% were white, 6% were black, 5% were Hispanic and 4% were other non-white race. The mean age was 79 years and 58% were females. The proportion of patients receiving anticoagulation within 90 days of AF diagnosis decreased from 45% in 2011 to 40% in 2013. Overall, blacks and Hispanics were less frequently anticoagulated compared to whites (35%, 39% and 45% respectively). Females were also less likely to receive anticoagulation compared to males (45% versus 41% respectively). The use of NOAC’s increased from 27 % of patients who received anticoagulation in 2011 to 44% in 2013. Among anticoagulated patients, blacks and Hispanics were less likely to receive NOACs compared to whites (25% and 30% Vs 36%), and females compared to males (34% vs 36%).

Conclusions:
In this retrospective study of Medicare patients with newly diagnosed AF, we noted an increase in the use of NOAC’s from 2011 to 2013, but a decrease in the proportion of patients receiving anticoagulation. This highlights the importance of educating health care providers regarding AF and stroke prevention. Blacks or Hispanics and females were less likely to receive any anticoagulation or anticoagulation by an NOAC, compared to whites and males respectively.