bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13803: Integration of Stroke Volume Index Into Clinical Decision Making for Patients With Suspected Severe Aortic Stenosis and Preserved Ejection Fraction: A Systematic Review of Evidence and Meta-Analysis
Authors: Bavishi Chirag , Balasundaram Kiruthika , Argulian Edgar
Published: April 2024

Introduction:
The 2014 ACC/AHA valvular disease guidelines recommend estimation of stroke volume index (SVI) by echocardiography in patients with suspected low-gradient severe aortic stenosis (SAS) and preserved left ventricular ejection fraction. We explored the evidence base for this recommendation by comparing the natural history of the disease in subgroups of low gradient aortic stenosis patients with high gradient patients.

Methods:
Pubmed, Embase and Scopus databases were searched for all studies that have compared natural history of SAS with preserved LVEF in flow-gradient patterns. We studied the following 3 groups: high gradient (HG), low-flow low-gradient (LFLG), and normal-flow low-gradient (NFLG). Random effects model was used to pool individual study results. The end-point was long-term all-cause mortality.

Results:
A total of 7 studies with 3,954 patients fulfilled the criteria. Compared to HG SAS, both LFLG and NFLG patients had a higher burden of comorbidities such as atrial fibrillation, coronary artery disease, and hypertension. Also, end-diastolic volume index was smaller for LFLG patients and indexed aortic valve area larger for NFLG patients. All-cause mortality was similar between HG and LFLG groups [Relative risk (RR): 1.27, 95% confidence interval (CI): 0.85 -1.91, p=0.24], while patients with NFLG had significantly lower all-cause mortality compared to HG group [RR: 0.63, 95% CI: 0.44-0.89, p=0.009].

Conclusions:
Compiled evidence supports using SVI in patients with suspected low gradient SAS. All analyses revealed high heterogeneity and further high-quality studies are necessary.
Abstract 13819: Cancer After Heart Transplantation: Incidence, Risk Factors and Prognosis
Authors: Van Keer Jan , Droogne Walter , Van Cleemput Johan , Vörös Gábor , Rega Filip , Meyns Bart , Janssens Stefan , Vanhaecke Johan
Published: April 2024

Introduction:
Malignancy is a major cause of morbidity and mortality after heart transplantation. We determined incidence, risk factors and prognosis of cancer after heart transplantation in a large single center cohort with long-term follow-up.

Methods:
We retrospectively analyzed all patients undergoing heart transplantation at our institution between January 1987 and December 2013. Patients who died within the first month of transplantation were excluded. All remaining patients were followed up until death or December 2014 for development of cancer.

Results:
Five hundred and forty-one patients were followed up for a mean of 10.7 ± 6.7 years. Cancer was diagnosed in 181 patients, at a mean of 7.7 ± 5.0 years after transplantation. Cumulative incidence of any cancer at 1, 5 and 10 years was 2 %, 14 % and 29 %, respectively. Almost half of all cancers were skin tumors (83 patients), squamous-cell carcinoma (57 patients) being more frequent than basal-cell carcinoma (51 patients). The most frequent non-skin cancer was lung cancer (41 patients), followed by lymphoma (30 patients) and prostate cancer (25 patients). Several patients had more than one cancer. Age at transplantation older than 50 years (HR 3.3, p < 0.001), male gender (HR 2.1, p = 0.001), ischemic etiology for transplantation (HR 1.4, p = 0.02), transplantation era before 2000 (HR 1.4, p=0.04), azathioprine versus mycophenolate (HR 1.4, p= 0.04) and cyclosporine versus tacrolimus as initial immunosuppression (HR 1.7, p = 0.005) were significant risk factors for post-transplant malignancy in a univariate Cox proportional hazards model. Of these, age at transplantation and male gender were independent risk factors in multivariate analysis. Median patient survival after diagnosis of cancer was 2.9 years for patients with non-skin cancer, versus 13.1 years for patients with only skin cancer (p < 0.001).

Conclusions:
This study highlights the importance of cancer after heart transplantation. Older recipient age at transplantation and male gender were independent risk factors in multivariate analysis. Strategies to individualize immunosuppression according to the patient’s needs could potentially help reduce this important cause of morbidity and mortality after heart transplantation.
Abstract 13921: Dysfunctional Bone Morphogenetic Protein Signaling Interlinks With Interleukin-1ß Mediated Inflammation in Pulmonary Arterial Hypertension
Authors: Pickworth Josephine A , Shay Sheila , Gladson Santhi , Iremonger James , Rothman Alex M , Francis Sheila , West James , Lawrie Allan
Published: April 2024

Rationale:
Bone morphogenetic protein receptor type 2 (BMPR2) mutations are found in heritable and idiopathic pulmonary arterial hypertension but disease penetrance is incomplete implying the necessity for a ‘second hit’. IL-1ß and IL-6 are increased in PAH patients and animal models and are proposed to play a critical role in disease.

Objective:
To determine pulmonary specific interplay between BMPR2 and IL-1ß signaling by exploring differences between pulmonary artery and aortic smooth muscle cells (PA / Ao SMC) in response to IL-1ß, and determine the effects of reduced BMPR2 expression using in vitro and in vivo disease models.

Methods and Results:
Microarray analysis of PASMC and AoSMC mRNA show reduced inflammatory pathway activation in response to IL-1ß in PASMC compared with AoSMCs. Pathway analysis identified an exaggerated inflammatory response to IL-1ß in PASMC lacking BMPR2 (siRNA). Significant up-regulation of IL-6, IL-1α and adhesion molecules (>2-fold) shown by array analysis was validated by qPCR. In the absence of BMPR2 a 1.5-fold increase in proliferation was observed in response to IL-1ß that is not present in PASMC with functional BMPR2. To study this further, R899X+/- BMPR2 transgenic mice were fed western diet for six weeks and given daily injections of IL-1ß. Mice were assessed for inflammatory activation and PAH phenotype (catheter/echo). mRNA and protein changes were measured by TaqMan PCR, western blotting and serum ELISA. Mice treated with IL-1ß had significantly higher white blood cell counts (1.7-fold), and showed trends for increased mRNA of VCAM1, IL-1α (whole lung) and significantly raised serum protein levels of IL-6 and OPG matching in vitro data. IL-1ß treated mice had an increase in early pulmonary vascular remodelling and the full assessment of the inflammatory cell infiltrate in R899X+/- mice is currently underway.

Conclusion:
IL-1ß induces a pulmonary artery specific transcriptome that is altered by suppression of BMPR2 signaling in vitro. In vivo and in vitro IL-1ß drives an exaggerated inflammatory response under conditions of reduced BMPR2 signaling. This research highlights a mechanism by which increased IL-1ß may provide a “second hit” to reduced BMPR2 signaling and stimulate or potentiate the development of PAH.
Abstract 14163: The Single Ventricle Reconstruction (SVR) Trial at 6 Years: Transplant-Free Survival, Catheter Interventions, and Morbidity
Authors: Newburger Jane W , Sleeper Lynn A , Gaynor J. W , Hollenbeck-Pringle Danielle , Frommelt Peter , Li Jennifer , Mahle William T , Williams Ismee A , Atz Andrew M , Burns Kristin M , Chen Shan , Cnota James F , Dunbar-Masterson Carolyn , Ghanayem Nancy S , Goldberg Caren S , Jacobs Jeffrey P , Lewis Alan B , Mital Seema , Pizarro Christian , Eckhauser Aaron W , Stark Paul , Ohye Richard G ,   for the Pediatric Heart Network Investigators
Published: April 2024

Background:
In the SVR trial, 1-year (y) transplant (tx)-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS)
vs
modified Blalock-Taussig shunt (MBTS). At 6 y, we compared tx-free survival, unplanned interventions, morbidities, New York Heart Association (NYHA) Class, and RV ejection fraction (RVEF) by assigned shunt.

Methods and Results:
The SVR trial treated 549 pts. Vital status and medical history were ascertained annually. Tx-free survival in the RVPAS (63.5%)
vs
MBTS (58.7%) groups did not differ (Figure; log-rank P=.13). Similarly, neither mortality nor tx alone differed by shunt type. By 6 y, RVPAS pts had a higher incidence of any catheter intervention (.38
vs
.23/pt-yr, P<.001), balloon angioplasty (P=.014), stent (P=.009), and coiling (P<.001). The % of pts with morbidities by 6 y were similar in the groups, with overall rates: pacemaker 3%, thrombosis 16%, stroke 7%, seizures 13%, protein losing enteropathy 3%, plastic bronchitis 0.5%, and 6-y NYHA Class I 71%, II 21%, III 3%, and IV 5%. Among pre-specified subgroups, worse tx-free survival was associated with low birth weight (<2500 g); worse pre-Norwood tricuspid regurgitation (≥2.5 mm jet width); lower surgeon Norwood volume; preterm birth (<37 wks); and combined aortic atresia and pre-term birth (all P<.01). Subgroup x shunt interaction was significant only for surgeon volume levels (P<.05); in the highest volume group (n >15/y), the MBTS was beneficial (P<.04), and in 3 lower volume groups, the RVPAS was qualitatively better. In 6-y echoes read to date, RVEF was similar in the RVPAS
vs
MBTS groups (46±7, n=55
vs
46±6%, n=48; P=.9).

Conclusions:
By 6 y, tx-free survival was an absolute 4.8% higher for pts assigned to the RVPAS
vs
MBTS group, but the difference no longer reached statistical significance, and they needed more catheter interventions. Rates of death, tx, and morbidities; distribution of NYHA Class; and RVEF were each similar in the shunt groups.
Abstract 14351: Increased Levels of IgM Autoantibodies to Oxidation-Specific Epitopes are Inversely Associated With Coronary Heart Disease: Analyses of Data From 204,257 Participants
Authors: Taleb Adam , Zhao Wei , Shahzada Amir , Rasheed Asif , Binder Christoph J , Witztum Joseph L , Danesh John , Rader Daniel J , Tsimikas Sotirios , Saleheen Danish
Published: April 2024

Background:
Immunoglobulin M (IgM) autoantibodies to oxidation-specific epitopes (OSE) have been shown to be protective against atherosclerosis in animal models, but the data in human studies is controversial.

Objectives:
This study sought to determine the association between IgM autoantibodies to OSE and apolipoprotein B-100-immune complexes (apoB-IC) and risk of coronary heart disease through a Mendelian Randomization study design.

Methods:
IgM autoantibodies to malondialdehyde-low density lipoprotein (MDA-LDL), phosphocholine-modified bovine serum albumin (PC-BSA) and IgM apoB-IC were measured in 9,830 participants (4966 first-onset cases with myocardial infarction [MI] and 4864 age and sex-matched controls) in the Pakistan Risk of Myocardial Infarction Study (PROMIS). Analyses in association with MI were conducted using logistic regression models progressively adjusted for age, sex, center, self-reported ethnicity, tobacco use, waist-to-hip ratio, history of diabetes and hypertension and LDL-C levels. Genetic analyses (GWAS and exome-chip) were also conducted using additive models. Variants associated with GWAS levels of significance were further assessed for pleiotropy and used as instruments to assess causality with CHD risk using genetic data on 63,746 CHD cases and 130,681 controls from the CARDIoGRAMplusC4D consortium.

Results:
In PROMIS, compared to the bottom quintile, the odds ratio for MI among participants in the top quintiles of IgM MDA-LDL, IgM PC-BSA and IgM apoB-IC were: 0.62 ([95% CI. 0.55-0.70], p<0.001), 0.60 ([95% CI. 0.53-0.68], p<0.001) and 0.64 ([95% CI. 0.56-0.73], p<0.001], respectively. Genetic analyses identified several novel variants associated with circulating IgM MDA-LDL, IgM PC-BSA and IgM apoB-IC at GWAS levels of significance. In CARDIoGRAMplusC4D variants that exclusively increased circulating IgM autoantibodies were causally associated with reduced CHD risk (P<1x10-5).

Conclusions:
Increased levels of IgM autoantibodies to MDA-LDL and PC-BSA and IgM apoB-IC are likely causally associated with a protective effect on CHD. This inverse association supports the hypothesis of the atheroprotective role of IgM autoantibodies.
Abstract 14726: Right Ventricular Strain Analysis May Be Useful in Differentiating Takotsubo Cardiomyopathy From Left Anterior Descending Coronary Artery Disease
Authors: Cai LiYing , Addetia Karima , Mor-Avi Victor , Spencer Kirk
Published: April 2024

Background:
Takotsubo cardiomyopathy (TTC) is a transient form of left ventricular (LV) dysfunction triggered by significant physiological stress and associated with a distinctive pattern of regional LV dysfunction on echocardiography. This pattern can be similar to and therefore difficult to differentiate from that seen in left anterior descending coronary artery (LAD) occlusion. We hypothesized that right ventricular (RV) involvement as detected by RV free-wall longitudinal strain (FWLS) might help differentiating TCC from LAD infarction.

Methods:
44 patients with TTC and 36 with LAD infarct were studied. The RV focused view was used to measure TAPSE (M-mode), S’ (pulsed-wave Doppler), and fractional area change (FAC). RVFWLS was measured offline (Epsilon). Apical 2-, 3- and 4-chamber views were used to measure LV longitudinal strain (LS) (QLAB) and biplane Simpsons was used to assess LV ejection fraction (EF).

Results:
LVEF was 31±10% in TTC and 41±9% in the LAD group. There was no significant difference in global LV LS between the two groups. Regional differences were noted with lower strain values in the mid and apical inferior, posterior and lateral segments in TTC. RV FAC, TAPSE, and S’ were lower in the TTC group than the LAD group. Overall RV FWLS was significantly lower in TTC than LAD infarct group (-18±8 vs -23±6%, p<0.05). This was due to marked reduction in apical LS (-10±8 vs -15±7%; p=0.002) with no significant differences in mid and basal LS (-19±11 vs -23±9% and -26±13 vs -30±12%, respectively). ROC analysis showed apical RVFWLS to be the best predictor for TTC with area under the curve (AUC) 0.73 (Fig).

Conclusion:
The regional pattern of RV dysfunction as assessed by FWLS revealed predominately reduction in the apical segments, and sparing of function in the mid and basal segments. Our results suggest that RV involvement should be more carefully evaluated in clinical practice when TTC is suspected as it may help differentiate this condition from LAD disease.
Abstract 14823: Adult Congenital Heart Disease is Associated With a Decreased Prevalence of Morbid Obesity
Authors: Lerman Joseph B , Doucette John T , Parness Ira A , Shenoy Rajesh U
Published: April 2024

Introduction:
Obesity may be associated with greater morbidity in adults with Congenital Heart Disease (ACHD), than in the general population. While obesity prevalence in pediatric CHD has been well studied, the prevalence of obesity in the American ACHD population is unknown. Our study seeks to determine the prevalence of obesity (BMI > 30) and morbid obesity (BMI > 35) in a cohort of ACHD patients, as compared to matched controls.

Hypothesis:
We assessed the hypothesis that ACHD is associated with a higher prevalence of obesity compared to controls.

Methods:
Retrospective analysis was performed on all ACHD patients (identified via ICD-9 coding) seen at a tertiary center in 2013. A control group without CHD was randomly created, matching for age, sex, and ethnicity.

Results:
1459 ACHD patients met inclusion criteria. ACHD patients had a lower mean BMI than controls (-0.650 kg/m2, 95% CI -1.068 to -0.231, p <0.002). Obesity prevalence did not differ significantly between groups: 25.6% in ACHD, 27.4% in controls (OR 0.909, 95% CI 0.766 to 1.079, p = 0.285). ACHD was associated with lower prevalence of morbid obesity (OR =0.656, CI 0.511 to 0.841, p < 0.0001), and higher prevalence of being underweight (BMI < 18.5) (OR 1.709, 95% CI 1.098 to 2.663, p < 0.016). ACHD was also associated with a lower prevalence of obesity amongst 41-65 year olds (OR = 0.722, 95% CI from 0.561 to 0.929, p < 0.011). Severity of CHD (classified as simple vs. complex) was not significantly related to obesity prevalence.

Conclusion:
In conclusion, ACHD is associated with a decreased prevalence of morbid obesity, and an increased prevalence of being underweight. ACHD is not significantly associated with obesity prevalence.
Abstract 14830: Cellular Iron Transport Protein, Transferrin Receptor 1 Plays an Important Role in the Pathophysiology of Chronic Kidney Disease
Authors: Oboshi Makiko , Naito Yoshiro , Sawada Hisashi , Iwasaku Toshihiro , Okuhara Yoshitaka , Morisawa Daisuke , Eguchi Akiyo , Nishimura Koichi , Soyama Yuko , Hirotani Shinichi , Mano Toshiaki , Ishihara Masaharu , Tsujino Takeshi , Masuyama Tohru
Published: April 2024

Background:
Cellular iron transport protein, transferrin receptor 1 (TfR1) is required for the uptake of transferrin-bound iron into the cells. Several reports have shown that iron accumulation is associated with the pathophysiology of chronic kidney disease (CKD); however, the role of TfR1 in the pathophysiology of CKD remains unknown. Herein, we investigate TfR1 in the experimental models of CKD.

Methods and Results:
CKD was induced by 5/6 nephrectomy in Sprague-Dawley rats. CKD rats showed proteinuria and tubular dilatation. Of note, TfR1 expression is increased in the remnant kidney along with increased iron accumulation, as compared with controls. To investigate the functional importance of TfR1 in the pathophysiology of CKD, we subjected to 5/6 nephrectomy in TfR1 hetero knockout mice. At 8weeks after 5/6 nephrectomy, systolic blood pressure was similar in TfR1 hetero knockout mice and wild-type (WT) littermates. In contrast, urinary albumin excretion, serum BUN, and creatinine levels were increased to a lesser extent in TfR1 hetero knockout mice compared with WT littermates. In addition, renal fibrosis was observed in the remnant kidney in WT mice, while the extent was attenuated in TfR1 hetero knockout mice. Consistent with these findings, increased renal gene expression of collagen type I and collagen type III were attenuated in TfR1 hetero knockout mice compared with WT littermates.

Conclusions:
These results indicate that TfR1 plays a role in the pathophysiology of CKD. Understanding the role of TfR1 in the pathophysiology of CKD may lead to a novel therapeutic approach for CKD.
Abstract 14861: Dual Mode Regulation of Directional Cell Migration by AMPK Using Two Substrates With Distinct Kinetics
Authors: Yan Yi
Published: April 2024

Introduction:
Striking feature of the regulation of cell migration by AMP-activated protein kinase (AMPK) activity level is that both suppression and augmentation of AMPK inhibit cell migration.

Hypothesis:
We have previously revealed that AMPK inhibition perturbs cell migration through the destabilisation of the microtubule cytoskeleton via de-phosphorylation of the microtubule plus-end protein CLIP-170. However, the mechanism for how AMPK activation also perturbs cell migration still remains unknown.

Methods and Results:
Here we used LC/MS to identify a novel substrate of AMPK: PDZ and LIM domain 5 (PDLIM5) is specifically phosphorylated only when AMPK activity is increased. Vascular smooth muscle cells expressing the phosphomimetic PDLIM5 mutant showed perturbed cell migrations accompanied by enlarged focal adhesions and enhanced stress fibre formation without disturbing the microtubule structures. Interestingly, the phosphorylation of PDLIM5 reduced its affinity for α-actinin, which may mechanistically contribute to actin cytoskeleton reorganisation and consequentially the inhibition of cell migration.

Conclusions:
We proposed the dual mode model, which regulates the directional cell migration of AMPK using the two substrates CLIP-170 and PDLIM5, with distinct activation kinetics to regulate cell migration separately by sensing the level of AMPK activity between two extremes.
Abstract 14866: Athletic Heart Screening: Usefulness of Echocardiography and Economic Impact
Authors: Bendaly Edgard
Published: April 2024

Background:
The athletic heart screen (AS) for sudden cardiac death (SD) detection is controversial in the USA. EKG use is common in AS programs but ECHO is uncommon. Our study aims to determine the effectiveness of ECHO in identifying athletes at risk for SD that would have been missed without ECHO and to evaluate the cost of AS.

Methods:
AS and medical records were reviewed. AS consisted of a self-completed questionnaire, EKG and limited ECHO. AS were abnormal at the discretion of the reader at the time they were reviewed. Data is expressed as percentage. Cost is calculated using average reimbursement for the ensuing initial cardiac evaluation.

Results:
In 10 years, 2016 AS were randomly assigned to 5 pediatric cardiologists. There were 336 (16.7%) abnormal AS. The rate of abnormal AS was 79/244 (12.1%), 19/190 (10%), 82/630 (31.2%), 7/63 (11%), and 164/889 (18.4%) for the reviewers, representing a wide variability in the percentage of abnormal AS among reviewers.

This resulted in 166 (49.4%) initial cardiac evaluations leading to 207 noninvasive testing in addition to repeat EKG in some cases. Testing included ECHO, Holter, stress test and cardiac CT and MRI. Initial evaluation was normal in 103 (62.0%) cases. Invasive interventions included: 3 small ASD closures, 1 moderate PDA closure, an EP ablation for WPW, and 1 surgery for abnormal right coronary artery origin (ARCA). In the remaining 57 (34.3%) cases, the cardiac abnormalities identified were mild including: prominent aortic root, premature complexes, and mild left-sided valve abnormalities in asymptomatic individuals. Conservatively, 2 diagnoses would be low risk for SD: WPW and ARCA representing <0.1% of all AS performed.

An abnormal AS was made by ECHO in 184/336 (54.8%) cases leading to 105 evaluations: 55 (52.4%) were normal, 45 (42.8%) had mild abnormalities, and 5 (4.8%) had the ASD and PDA closures, and the coronary surgery.

The cost of 2016 AS was $100,000. The cost of the 166 first evaluations performed including noninvasive testing was $160,462.

Conclusions:
AS results are reviewer-dependent and low yield for detecting conditions at high risk for SD. The addition of ECHO can identify mild congenital heart disease and coronary abnormalities at the expense of increasing costs, acutely and long term.
Abstract 14928: Efficacy and Safety of Transradial Multi-vessel Coronary Artery Disease Intervention as Compared With Single Vessel Disease Intervention
Authors: Choi Woong Gil , Rha Seung Woon , Kim Soo Hyun , Choi Byoung Geol , Choi Se Yeon , Oh Dong Joo ,   Korean TRI Working Group
Published: April 2024

Backgroud:
Transradial percutaneous coronary intervention (PCI) has evolved into a viable alternative to the traditional transfemoral approach. Clinical aspects related to transradial PCI on multi-vessel disease have been seldom investigated and reported. The aim of this study is to evaluate safety and efficacy of transradial intervention (TRI) for patients with multi-vessel disease as compared with single vessel disease.

Method:
A total of 1,690 consecutive patients underwent TRI were entered into multicenter Korean TRI Registry from Nov 2004 to Oct 2010. The patients were divided into two groups; Multi-vessel radial PCI group (n=424 pts) and Single vessel radial PCI group (n= 1266 pts). To adjust potential confounders, propensity score matched (PSM) analysis was performed using the logistic regression model (C-statics: 0.726). After PSM, total of 776 pts (388 pairs) were generated for this analysis. The primary study endpoint was 1-year major adverse cardiac event (MACE) defined as the composite of total death, myocardial infarction, target vessel revascularization (TVR) and stent thrombosis.

Result:
Baseline characteristics were well balanced between the two groups after PSM adjustment. At 1 year, the incidence of MACE was similar between the two groups (11.0% vs. 10.8 %, p=0.908, table). Although the multi-vessel radial PCI group had a longer procedure time (65.52±30.2 vs. 48.75±25.7 min, p<0.001) than the single-vessel PCI group, however, the incidence of contrast induced nephropathy was similar between the two groups (0.7% vs. 1.0%, p=0.725).

Conclusion:
In this study, although procedure time was longer in multi-vessel radial PCI group, transradial PCI was safe and effective in patients with multi-vessel disease. It might be favored over femoral artery as a primary access route for complex PCI.
Abstract 14938: Association Between Survival and Increases in Prehospital Systolic Blood Pressure After Its Nadir in Major Traumatic Brain Injury
Authors: Spaite Daniel W , Hu Chengcheng , Bobrow Bentley J , Sherrill Duane , Chikani Vatsal , Barnhart Bruce , Gaither Joshua B , Denninghoff Kurt R , Adelson P. D , Viscusi Chad , Mullins Terry , Stolz Uwe
Published: April 2024

Introduction:
Little is known about prehospital EMS blood pressure patterns in TBI and the effect of serial trends in BP during EMS care remains entirely unclear. Using the comprehensive, linked EMS data in the Excellence in Prehospital Injury Care (EPIC) TBI Study (NIH 1R01NS071049; ClinicalTrials.gov NCT01339702), we evaluated the association between mortality and increases in EMS systolic BP (SBP) after the lowest recorded SBP in major TBI cases.

Methods:
We used the entire EPIC pre-implementation cohort (before TBI guideline implementation; 1/07-3/14) to assess, in detail, a previous preliminary evaluation. All moderate/severe TBI cases (CDC Barell Matrix Type 1) were evaluated [exclusions: age <10, died before ED arrival, SBP <40 or >300, missing SBP (4%)]. Logistic regression was used to determine associations between increases in EMS SBP after the lowest SBP and the probability of death, adjusted for important confounders.

Results:
Among 14,567 included cases, 7696 (68% male, median age 45) were in the cohort of interest (had an equal or higher SBP recorded subsequent to the lowest). Figures show the probability of death vs the increase after the nadir (and 95% CIs) in 4 cohorts of lowest SBP (40-89; 90-139; 140-159; 160-300).

Conclusion:
Increases in EMS SBP after the nadir revealed distinct patterns: Hypotension-Mortality drops significantly if SBP increases after the nadir (dramatic improvement with large increases). Normotension-Mortality is slightly reduced with SBP increases and even large increases were not detrimental. Mild HTN-Mortality decreases with modest SBP increases but large increases (>40mmHg) are associated with higher mortality. Severe HTN-Higher mortality with any subsequent increase. The findings in the hypotensive & normotensive cohorts support the concept of restoring/optimizing cerebral perfusion in TBI. This is further supported by the fact that, even with mild HTN, moderate SBP increases do not appear to be detrimental.
Abstract 15057: Cardiovascular Outcomes and Stroke Rates in Hospitalized Patients With Cancer and Atrial Fibrillation-A Study Using the 2012 National Inpatient Sample
Authors: Sullivan Malachy , Shatzel Joseph , Friedman Scott E , Palac Robert T , Gemignani Anthony
Published: April 2024

Background:
Patients with cancer (CA) who develop atrial fibrillation (AF) have increased morbidity and mortality. CA is associated with venous thromboembolism (VTE), however its impact on stroke rate is unclear. The efficacy of the CHADS2 score in assessing stroke risk in patients with AF and CA is unknown. This study compares clinical characteristics, cardiovascular outcomes and stroke rate in hospitalized patients with AF and CA versus those with AF without CA.

Methods:
Using the 2012 National Inpatient Sample (NIS), we identified admissions in patients >18 years associated with AF. Patients with active CA were then identified. Clinical characteristics and cardiovascular outcomes including stroke rate were collected.

Results:
Of the 7,296,968 admissions in the 2012 NIS, 751,009 (10.3%) were associated with AF. Patients with CA represented 10.4% (78,099) of admissions with AF. The most common cancers were lung (18.6%), lymphoma (8.1%), leukemia (8.5%), and prostate (8.0%). Patient characteristics (Table 1) were all significantly different to a p value of <0.001, with the exception of tobacco use.

Patients with AF and CA had fewer cardiovascular events (Table 2) except for VTE. Those with AF and CA also had longer lengths of stay and higher mortality. There were statistically significant differences (p <0.001) in all clinical outcomes.

Conclusion:
Atrial fibrillation in patients with cancer is associated with adverse outcomes, including venous thromboembolism, length of stay and mortality but is not associated with increased rate of stroke. In patients with cancer and atrial fibrillation increasing rate of stroke was associated with increasing CHADS2 score.
Abstract 15182: Factors Associated With Aortic Dissection in Patients With
TGFBR1
Or
TGFBR2
Mutations: Results From the Montalcino Aortic Consortium
Authors: Jondeau Guillaume , Ropers Jacques , Regalado Ellen , Braverman Alan , Evangelista Arturo , Teixedo G , De Backer Julie , Naudion Sophie , Zordan Cecile , Morisaki Takayuki , Morisaki Hiroko , Muino Mosquera L , von Kodolitsch Yskert , Dupuis-Girod Sophie , Morris Shaine A , Jeremy Richmond , Odent Sylvie , Langeois Maud , Spentchian Myrtille , Milleron Olivier , Boileau Catherine , Pyeritz Reed , Milewicz Dianna ,   Montalcino Aortic Consortium
Published: April 2024

Introduction:
Natural history of patients with
TGFBR1
or
TGFBR2
mutations is not well known

Hypothesis:
Physical features may indicate high risk patients

Methods:
Data were collected on 403 patients with either
TGFBR1
or
TGFBR2
mutations. We compared the phenotypic features of patients with and without aortic dissection.

Results:
Patients with aortic dissection were diagnosed when older, suggesting delay in diagnosis being one of the main parameter related to the occurrence of this deadly complication.

Features of Loeys Dietz Syndrome (arterial tortuosity, hypertelorism, broad or bifid uvula and wide scars) were more frequently associated with dissection,suggesting that these features may help identifying high risk patients, in whom aortic surgery may have to be proposed earlier.

In contrast, the systemic score proposed for the diagnosis of Marfan syndrome was not helpful in recognizing high-risk patients.

Of note, a systemic score ≥ 7 was present in 1/5 of the population.

The risk of aortic dissection was similar in patients carrying a
TGFBR1
mutation or a
TGFBR2
mutation (35/159 (22%) vs. 57/244 (23%). However,

- The last maximal aortic root diameter before or at the time of type A aortic dissection was greater in
TGFBR1
than in
TGFBR2
(65 (22) vs. 50 (12)mm ; p= 0.039).

- Type B aortic dissection was less frequently reported in
TGFBR1
(6% vs 12% of the patients)

- Lastly aortic event (surgery or dissection) occurred more frequently in males than in females carrying a
TGFBR1
mutation {53.7% of males (median age 27 years [21-39]) and 29.3% of females (34 years [28-44]), p=0.003} but not a
TGFBR2
mutation (46.2% of males (median age 32 [20-41]) and 40.5% of females (30 years [19-42], NS}

Conclusions:
Aortic dissection was associated with delayed/unknown diagnosis, and the presence of clinical features of LDS. The prevalence for aortic events differs between men and women with
TGFBR1
mutation but not
TGFBR2
mutations
Abstract 15317: Deletion of Low Molecular Weight Protein Tyrosine Phosphatase (Acp1) Protects Against Stress-induced Cardiomyopathy
Authors: Mahmoud Salma , Wade Fallou A , Quijada Pearl , Mohamed Adib Al-Haffar Kamar A , Kunhi Muhammad A , Toko Haruhiro , Marashly Qussay , Belhaj Karim , Ibrahim Esra , Stanford Stephanie M , Alvarez Roberto , Liu Yingge , Colak Dilek , Jordan Maria C , Roos Kenneth P , Al-Habeeb Waleed A , Sussman Mark , Bottini Nunzio , Poizat Coralie
Published: April 2024

Background:
The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the
ACP1
gene, is a ubiquitously expressed phosphatase whose
in vivo
function remains poorly understood. Genetic studies revealed an association between
ACP1
and a variety of human cardiovascular disorders. However, evidence of a direct involvement of LMPTP in cardiac diseases is still lacking.

Methodology:
We generated the first mouse model of Lmptp deficiency and studied the response of the mice under basal condition or to long-term pressure overload using comprehensive experimental approaches such as q-PCR, siRNA technology, fluorescent microscopy and immuneprecipitation technique.

Results:
Acp1

-/-

mice develop normally, and aging mice do not show any obvious signs of pathology in major tissues under basal condition. However,
Acp1

-/-

mice are strikingly resistant to pressure overload hypertrophy and heart failure. Lmptp expression is high in the embryonic mouse heart, decreased in the post-natal stage, and increased in the adult mouse and human failing heart. Consistent with their protected phenotype,
Acp1

-/-

mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of hypertrophic markers. Transcriptional profiling and analysis of molecular signaling shows that the resistance of
Acp1

-/-

mice to pathological cardiac stress correlates with marginal expression of fetal cardiac genes, increased insulin receptor beta phosphorylation and inactivation of CaMKIIδ pathway.

Conclusion:
Our data show that ablation of Lmptp inhibits pathological cardiac remodeling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of heart failure in human.
Abstract 15383: Clinical Features and Prognosis of Patients Who Survived Ventricular Fibrillation Due to Coronary Artery Spasm
Authors: Nakayama Naoki , Akiyama Eiichi , Iwahashi Noriaki , Maejima Nobuhiko , Tsukahara Kengo , Hibi Kiyoshi , Ebina Toshiaki , Sumita Shinichi , Kimura Kazuo , Umemura Satoshi
Published: April 2024

Introduction:
Coronary artery spasm can lead to lethal arrhythmia and sudden cardiac death. The aim of this study was to elucidate the clinical features and prognosis of patients who survived cardiac arrest due to coronary artery spasm.

Methods:
We retrospectively studied consecutive patients who survived ventricular fibrillation out of hospital cardiac arrest due to coronary artery spasm, and discharged neurologically intact.

Results:
Nineteen patients (18 men and 1 woman, mean age 55 ± 10 years) were enrolled. In all patients, ventricular fibrillation (VF) was documented as the initial rhythm at cardiac arrest. Transient ST-segment elevation during spontaneous attack was observed in 9 patients. Acetylcholine provocation tests were performed and resulted in positive in 15 patients. In 11 patients, cardiac arrest was the first episode of vasospastic attack. All patients were treated with vasodilators including calcium channel blockers. An implantable defibrillator (ICD) was implanted in 12 patients according to the discretion of the attending physician. During a mean follow-up interval of 42 months, 4 episodes of VF were observed in 3 patients and ST-segment elevation myocardial infarction (STEMI) was observed in 1 patient. Two episodes of VF were occurred before the diagnosis of coronary artery spasm was confirmed during the index hospitalization, and the other 2 VF were occurred after ICD implantation. All VF were treated by manual defibrillation or ICD shocks. None of patients developed cardiovascular death. There are no differences in the characteristics of the patients between those with and without recurrence of VF and STEMI. However, medications against coronary artery spasm were discontinued before the cardiac events in all episodes of VF and STEMI. The intervals between cessation of medications and cardiac events were less than 2 days in all cardiac events.

Conclusions:
The patients who survived cardiac arrest due to coronary artery spasm were at high risk for recurrence of severe ischemia and lethal arrhythmia. Cessation of medication, even within a few days, was closely associated with cardiac events. ICD therapy may be beneficial in patients who survived cardiac arrest due to coronary artery spasm.
Abstract 15462: Gender-related Outcomes of Thoracic Endovascular Aortic Repair for Descending Thoracic Aortic Aneurysms
Authors: Orejola Wilmo C , O'Connor David J , Liu Yeu , Nyirenda Themba , Wilderman Michael J , Elmann Elie M , Napolitano Massimo M , Simonian Gregory T
Published: April 2024

Objectives:
To review and re-evaluate the poor outcome of thoracic endovascular repair in women at our institution.

Methods and Materials:
We reviewed our data on thoracic endovascular aortic repair from 2006 to 2014 for descending thoracic aortic aneuryms only. Pre-operative comorbidities, size of aneurysm, endograft usage, postoperative complications and mortalities were compared. A 24-month follow-up data was plotted in Kaplan-Meier survival curve.

Results:
There were 26 women and 21men, mean ages 81.7 ± 6.8 years and 72.8 ± 11.9 years (p < .004), respectively. Average aortic size was 6.2 cm and 4 (5.7%) ruptured aneurysms in women and 5.5 cm with only one noted rupture in men. Congestive heart failure as comorbidity showed a higher risk of death associated with TEVAR by logistic regression analysis. Less than 30 days mortality was 2 (7.7%) and > 30 days 6 (23%) in the women group. There were no early or late deaths in the men group (p < 0.0056). Deaths were only in women.

Kaplan-Meier curve showing comparative 24-month survival between gender. The 24-month overall survival was 100% for males and 23.3% for females. Lack of mortality events among males resulted in no hazard ratio and 95% confidence interval for HR for gender.

Conclusion:
Congestive heart failure as comorbidity poses a greater risk of death postoperatively in TEVAR. Women undergoing TEVAR have greater mortality risk than men, because of larger size of the aneurysm and incidence of rupture during intervention.
Abstract 15486: The Association of Susceptibility Genes of Abdominal Aortic Aneurysm and Atherosclerotic Cardiovascular Disease With Risk for All-cause Mortality
Authors: Ye Zi , Austin Erin , Arruda-Olson Adelaide M , Kullo Iftikhar J
Published: April 2024

Introduction:
Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death worldwide. The genetic contribution to mortality in patients with ASCVD is unknown.

Hypothesis:
Abdominal aortic aneurysm (AAA) often co-exists with ASCVD and two with shared genetic susceptibility underlying disease development. We hypothesiz that a genetic risk score (GRS) for susceptibility variants to AAA and ASCVD increases the risk for all-cause mortality in patients with ASCVD.

Methods:
We analyzed high-density genotyping data in 3053 participants (age 71 ±10 years, 72% men) with ASCVD in Mayo Vascular Disease Biorepository. We used 4 single nucleotide polymorphisms (SNPs) (rs2383207, rs7025486, rs599839, rs1466535) previously shown to be associated with AAA and ASCVD at GWAS significance (P ≤10^-8) in the NHGRI GWAS catalog to build the GRS. We defined ASCVD as a history of myocardial infarction / coronary revascularization / ischemic stroke / peripheral arterial disease with revascularization.

Results:
Patients with GRS > median level had similar age (70±10 vs. 71±10), prevalence of men (72% vs. 73%), hypertension (83% vs. 82%), diabetes (32% vs. 31%) and smokers (74% vs. 72%) compared to those with GRS ≤ median (all P>0.2), except for dyslipidemia (91% vs. 88%, P =0.02). After a median follow-up of 4.56 years (interquartile: 3.07-6.26), 620 patients died. Patients with GRS > median had poorer survival compared to those with GRS ≤ median (Figure: Kaplan-Meier curve); and with 23% higher risk for death after adjustment for age, sex and cardiovascular risk factors (hazard ratio HR, 95% CI: 1.23, 1.05-1.45). The association of GRS with all-cause mortality remained significant after excluding patients with known AAA (n=672) (HR, 95%CI: 1.22, 1.01-1.48).

Conclusions:
A GRS for susceptibility variants of AAA and ASCVD is a prognostic marker in patients with ASCVD.
Abstract 15582: Cardiovascular Risk Factors in Breast Cancer Survivors: Analysis of NHANES 1999-2012
Authors: Hassoon Ahmed , Appel Lawrence , Maruthur Nisa , Yeh Hsin-Chieh
Published: April 2024

Introduction:
There are 2.8 million breast cancer survivors in the U.S. With improved survival from breast cancer, cardiovascular disease has emerged as one of the leading causes of morbidity and mortality. However, few studies have assessed CVD risk factors among breast cancer survivors.

Methods:
We analyzed the National Health and Nutrition Examination Survey (NHANES) 1999-2012 to assess CVD risk factors, as defined by AHA/ACC, in adult women with and without a history of breast cancer.

Results:
A total of 537 women, age 20 and older, with breast cancer history and 17,902 women without cancer history were included in the analysis. Among women with breast cancer, the mean (SE) age at diagnosis was 56y (0.81). 32.8% had the diagnosis < 5 years; 39.9% survived more than 10 years after diagnosis. Compared to women without cancer, the breast cancer survivors were older (mean age 65 (0.80) vs 46 (0.23)), and more likely to be white (84.2% vs. 67.6%) (both p<0.0001), but with similar education level. In stratified analyses, after adjustment for age, black women with breast cancer compared to black women without cancer history had significantly higher SBP (128.9 vs 124.5, p=0.003), and were more likely to be obese, have hypertension and diabetes (Table). In contrast, there were no significant differences in CVD risk factors in non-black women. There were no differences in lipids profiles between women with and without breast cancer.

Conclusion:
CVD risk factors are very prevalent in breast cancer survivors. Improving cardiovascular health through lifestyle change and preventive strategies, particularly in black women with breast cancer, is a public health priority.
Abstract 15740: Aortic versus Carotid Arterial Stiffness in Systemic Lupus Erythematosus: Are They Simultaneously or Divergently Associated With Cerebrovascular Disease?
Authors: Roldan Paola C , Roldan Luis P , Greene Ernest R , Qualls Clifford R , Sibbitt Wilmer L , Roldan Carlos A
Published: April 2024

Purpose:
Aortic and carotid stiffness and cerebrovascular disease (CVD) are common in systemic lupus erythematosus (SLE). However, it is unknown whether aortic and carotid stiffness are associated with CVD in a parallel or divergent fashion.

Methods:
43 SLE patients (41 women, age 36±11 years) and 17 age-and-sex matched healthy volunteers (14 women, age 34±12 years) prospectively underwent :1) transesophageal echocardiography and carotid ultrasonography for assessment of aortic and carotid stiffness, respectively, using the Pressure-Strain Elastic Modulus (PSEM) expressed in Pascal units; 2) assessment of CVD defined as acute stroke, neurocognitive dysfunction, or focal brain injury on MRI; and 3) follow-up for 45 months for assessment of incident stroke, cognitive disability, or death.

Results:
Aortic, but not carotid PSEM, was higher in SLE patients than in controls (7.96±4.16 versus 5.77±2.32 units, p=0.01 and 6.39±2.70 versus 5.55±2.68 units, p=0.29, respectively). Only aortic PSEM was positively associated with increased risk for prevalent CVD (OR=3.87, p=0.02) and incident CVD or mortality (OR=2.72, p=0.02) after simultaneously adjusting for atherogenic risk factors and antiphospholipid antibodies (Table 1).

Conclusion:
In young adult SLE patients, aortic stiffness in comparison to carotid stiffness is associated with a higher risk for prevalent CVD and incident CVD or mortality.
Abstract 11162: Hypothermia Attenuates Postresuscitation Myocardial Dysfunction by Inhibiting Beta Adrenergic Signaling
Authors: Wang Wei , Hua Tianfeng , Li Hao , Wu Xiaobo , Peberdy Mary A , Ornato Joseph P , Tang Wanchun
Published: April 2024

Introduction:
Therapeutic hypothermia reduce the severity of post-resuscitation myocardial dysfunction caused by epinephrine administered during cardiopulmonary resuscitation (CPR) , and the mechanism remains unclear.

Hypothesis:
hypothermia may reduce the concentration of cyclic adenosine monophosphate (cAMP), a second messenger of beta-adrenergic receptor activity.

Methods:
Thirty two male Sprague-Dawley rats were randomized to four groups: 1) normothermic placebo control; 2) normothermic epinephrine; 3) hypothermic placebo control; and 4) hypothermic epinephrine. Ventricular fibrillation was induced electrically and untreated for 8 mins. Hypothermia was initiated coincident with the start of CPR and maintained at 33 ± 0.2°C for 4 hrs after resuscitation and animals were then euthanized. Either placebo or epinephrine was administered 5 mins after the start of CPR and 3 mins before defibrillation. Post-resuscitation ejection fraction was measured hourly for 4 hrs. The hearts were then harvested for cAMP and Inositol 1,4,5-trisphosphate (IP3) assay analysis.

Results:
All animals were successfully resuscitated except one in normothermic placebo group. Epinephrine significantly increased coronary perfusion pressure during CPR (26.5±6.23mmHg
vs
21.14±1.95 mmHg P<0.05). Post-resuscitation myocardial function was significantly impaired in normothermic epinephrine group compared with other three groups (figure 1). The concentration of myocardial cAMP was double in normothermic epinephrine group (655.06±447.63 umol/L) when compared to that in hypothermic epinephrine group (302.51±97.98 umol/L P<0.05). However, there was no difference in the concentration of IP3 in all four groups.

Conclusions:
The potential mechanism of myocardial protective effect of hypothermia may involve the reduced activities of β-receptors.
Abstract 11176: SGLT-2-inhibition With Dapagliflozin Reduces Tissue Sodium Content
Authors: Schmieder Roland , Ott Christian , Linz Peter , Jumar Agnes , Friedrich Stefanie , Titze Jens , Hammon Matthias , Uder Michael , Kistner Iris
Published: April 2024

Introduction:
Sodium tissue content by
23
Na magnetic resonance imaging (Na-MRI) has been validated in experimental and human studies. SGLT-2 inhibition blocks the reabsorption of glucose and, in parallel, of sodium in the proximal tubular cells in a 1:1 fashion. We hypothesized that SGLT-2 inhibition in patients with type 2 diabetes leads to decreased tissue sodium content due to its pharmacological action.

Methods:
In a prospective, double blind, placebo controlled, cross-over trial 59 patients (61±7.6 years) with type 2 diabetes were randomized to dapagliflozin 10 mg o.d. and placebo for 6 weeks each. In addition to metabolic parameters and ambulatory blood pressure (BP) we analyzed the sodium content in the skin and muscles of the lower leg by the Na-MRI at baseline, after the first and second treatment phase of 6 weeks.

Results:
Compared to baseline 6 weeks treatment with the SGLT-2 inhibitor dapagliflozin decreased fasting (132±28 vs. 114±19mg/dl, p<0.001), postprandial blood glucose (178±66 mg/dl vs. 153±46mg/dl, p<0.001), body weight (87.6 vs. 86.6 kg, p<0.001) and systolic (129±12 vs. 126±11, p=0.010) and diastolic (77.4±9 vs. 75.6±8 mmHg, p=0.024) 24-hour ambulatory BP. Tissue sodium content in the skin was reduced after 6 weeks treatment with dapagliflozin compared to baseline (24.1±6.6 vs.22.7±6.4 mmol/L; p=0.013). No significant reduction of tissue sodium content was observed in the muscle (M. triceps surae: 20.5±3.5 vs. 20.4± 3.7 mmol/L, p=0.801). No clear significant difference in tissue water content of muscle and skin was observed after 6 weeks of treatment with dapagliflozin, compared to baseline.

Conclusions:
SGLT-2 inhibition with dapagliflozin resulted in a significant decrease in sodium tissue content of the skin after 6 weeks. This observation point to a decrease of total sodium content in patients with type 2 diabetes known to be salt sensitive and prone to cardiovascular complications, that might be mitigated by SGLT-2 inhibition.The Study was supported by AstraZeneca.