bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18468: Associations Between Clinical Characteristics and NT-proBNP in Heart Failure with Preserved Ejection Fraction: Data from the KaRen Study
Authors: Lund Lars H , Donal Erwan , Oger Emmanuel , Hage Camilla , Persson Hans , Haugen-Löfman Ida , Daubert Jean-Claude , Linde Cecilia
Published: April 2024

Purpose:
In heart failure with reduced ejection fraction, N-terminal pro brain natriuretic peptide (NT-proBNP) is useful for diagnosis and prognosis, and is higher with older age, female gender, renal failure and lower in obesity. In heart failure with preserved ejection fraction (HFPEF), NT-proBNP is also useful for diagnosis and prognosis, but clinical correlates are less well established.

Methods:
KaRen is a multicenter prospective registry of HFPEF. Inclusion criteria are acute presentation with Framingham symptoms and signs of heart failure together with NT-proBNP >300 ng/L and LVEF >=45%. The association between clinical characteristics and log NT-proBNP was assessed with uni- and multivariate linear regression, with backward step-wise selection based on p < 0.05.

Results:
We studied 400 patients, mean (SD) age 77 (9) years, 56% women. The table lists variables independently associated with log NT-proBNP, their baseline values and Beta coefficients.

Conclusions:
In HFPEF, NT-proBNP is determined mainly by NYHA class and clinical signs of heart failure. Clinical signs are important predictor of severity of disease. As in reduced ejection fraction, NT-proBNP is inversely associated with BMI and GFR, but unlike in reduced ejection fraction, it is not associated with age or gender.
Abstract 18477: Outcome of Anatomical Approach of Radiofrequency Catheter Ablation for Atrioventricular Nodal Reentrant Tachycardia: 15 years experience
Authors: Shim Jaemin , Wi Jin , Mun Hee-Sun , Uhm Jae-Sun , Hwang Hye Jin , Kim Jong Youn , Joung Boyoung , Pak Hui-Nam , Kim Sung Soon , Lee Moon-Hyoung
Published: April 2024

BACKGROUND:
Even though the anatomical approach as the radiofrequency (RF) ablation for atrioventricular nodal reentrant tachycardia (AVNRT) has been introduced long ago, large population based outcome of this approach remains unclear. Moreover, electrophysiologic characteristics between different successful target sites have not been identified as well. The purpose of this study was to investigate outcome and electrophysiologic characteristics according to successful target site.

METHODS:
A total of 1391consecutive patients (mean age 45±16 years, female 63%) who underwent RF catheter ablation based on anatomical approach for AVNRT between 1996 and 2010 were enrolled in this study. The tricuspid annulus between the coronary sinus ostium and the His bundle recording site was divided into posterior (P), medial (M), and anterior (A) regions. Serial RF energy applications were delivered from P site to superior side until junctional rhythm was inducible.

RESULTS:
Dual AV nodal physiology was documented in 91.9 %, typical AVNRT was 92.4 %. The mean procedure time, fluoroscopic time, and the ablation time was 63±28 min, 12±7 min, and 226±176 sec, respectively. Successful target site was P in 46.7% (n=684), M in 47.9% (n=701), and A in 0.7% (n=5). Long-term recurrence rate was 1.8% (n=25). AV nodal block requiring pacemaker occurred in 0.2 % (n=3). When divided into two groups, A (successful ablation at P site) and B (successful ablation at M and A sites), there was no difference between two groups in age, gender, tachycardia cycle length, atrial effective refractory period (ERP), AV block cycle length (BCL), ERP of fast and slow pathway, ventricular ERP, temperature, RF power, and long-term recurrence (all p values > 0.05). However, group A had more atypical form (9.4% vs. 6.0%, p=0.019), longer shortest VA interval (30.0±1.35 vs. 24.5±1.13 msec, p=0.002), longer VA BCL (376±102 vs. 361±88 msec, p=0.007), and shorter RF time (180±121 vs. 317±226 sec, p<0.001) than group B.

CONCLUSION:
Anatomical approach of RF ablation for AVNRT showed excellent long-term outcome. The electrophysiologic characteristics were different according to successful ablation site.
Abstract 18507: Impact of Sleep Disordered Breathing on Long-term Outcome in Patients with Acute Coronary Syndrome
Authors: Mazaki Toru , Yokoi Hiroyoshi , Iwabuchi Masashi , Nobuyoshi Masakiyo
Published: April 2024

Background:
There has been growing evidence associating sleep disordered breathing (SDB) with cardiovascular events. However, the impact of SDB on long-term outcome in patients with acute coronary syndrome (ACS) has not been fully evaluated.

Methods:
We performed an overnight cardio-respiratory monitoring in 361 patients with ACS who were successfully treated with percutaneous coronary intervention between December 2004 and November 2009. Patients with an apnea-hypopnea index≥5/hour were considered to have SDB. We defined major adverse cardiovascular events (MACE) as cardiovascular death, non-fetal myocardial infarction, stroke and admission for congestive heart failure. Patients were followed for a mean period of 3.8 years.

Results:
Comorbidity of SDB with ACS was found in 195 patients (54%). MACE-free survival rate was significantly lower in patients with SDB (76% vs. 89%, p=0.0084). Multivariate logistic regression analysis identified SDB (hazard ratio: 2.03, 95% CI: 1.02 to 4.06, p=0.045) and reduced cardiac systolic function (Ejection fraction < 45%) (hazard ratio: 3.42, 95% CI: 1.80 to 6.49, p<0.001) as independent predictors of MACE.

Conclusions:
Our study showed a high prevalence of SDB among patients with ACS and SDB appeared to be a valuable predictor for clinical outcome in them. This suggests that earlier diagnosis and intervention for SDB should be considered in patients with ACS.
Abstract 18522: Atrial Ganglionated Plexus Stimulation Prevents Myocardial Ischemia Reperfusion Arrhythmias by Preserving Connexin43 Protein
Authors: Yu Lilei , He Wenbo , Huang Bing , He Bo , Jiang Hong
Published: April 2024

Atrial ganglionated plexus Stimulation Prevents Myocardial Ischemia Reperfusion Arrhythmias by Preserving Connexin43 Protein

Background:
Vagal nerve stimulation has been shown to provide protective effect against ischemia/reperfusion (I/R) arrhythmias. Since atrial epicardial ganglionated plexuses contain a large amount of parasympathetic elements, we hypothesize atrial epicardial ganglionated plexus stimulation (GP-S) may be an alternative to vagal nerve stimulation for preventing arrhythmias induced by myocardial I/R.

Methods and Results:
Twenty one dogs were randomly divided into GP stimulation (GP-S) group (N=11) and control group (N=10). Myocardial I/R was induced by first 2 hours of reperfusion in dogs subjected to 45 minutes of ischemia with occlusion of the left anterior descending coronary artery (LAD). A bipolar plaque electrode was sutured overlying the fad pad containing the superior left ganglionated plexus (SLGP), which located at the junction of left pulmonary artery and left superior pulmonary vein.The GP-S was performed by applying high frequency electrical stimulation (HFS: 20Hz, 0.1msec duration) to the SLGP. The lowest voltage level of GP-S that induced approximately 10% sinus rhythm slowing was chosen as the voltage for GP-S. Compared with control group, GP-S caused significant increases in ventricular ERP and vagal indice (HF nu), as well as an evident decrease in sympathetic tone (LF/HF), the numbers of PVCs, salvos, and VT runs were significantly reduced in GP-S group. And the incidences of salvo and VT in GP-S group were significantly lower. Immunoblotting revealed that the control group showed a marked reduction in the amount of phosphorylated connexin43 (Cx43), whereas the GP-S group showed only a slight reduction. Immunohistochemistry confirmed that the myocardial I/R-induced loss of Cx43 from intercellular junctions was prevented by GP-S.

Conclusions:
GP-S protects against ventricular arrhythmias resulting from brief myocardial I/R by modulating connexin43. GP-S may serve as a non-pharmacological clinical approach to improve acute myocardial I/R arrhythmias such as during coronary bypass surgery.
Abstract 18571: Stroke and Outcomes in Patients with Acute Type A Aortic Dissection
Authors: Bossone Eduardo , Harris Kevin M , Suzuki Toru , Fattori Rossella , Hutchison Stuart , Ehrlich Marek P , Pyeritz Reed E , Steg P. Gabriel , Greason Kevin , Evangelista Arturo , Voehringer Matthias , Montgomery Daniel G , Isselbacher Eric M , Nienaber Christoph A , Eagle Kim A
Published: April 2024

Background: Stroke is one of the most dreaded complications of type A acute aortic dissection (TA-AAD). However, few data exist on its incidence and association with prognosis.

Methods: We evaluated 2202 TA-AAD patients [pts, mean age 61.9 ± 14.4, 1487 (67.5%) male] from the International Registry of Acute Aortic Dissection (IRAD) to determine the incidence and prognostic influence of stroke in TA-AAD.

Results: Stroke was present at arrival in 132 (6.0%) TA-AAD pts. Stroke pts were older (65±12 vs. 62±15 yrs; p=.002) and more likely to have hypertension (86% vs. 71%; p=.001) or atherosclerosis (29% vs. 22%; p=.042). While chest pain at arrival was less common (70% vs. 82%; p<.001), stroke pts presented more often with syncope (44% vs. 15%; p<.001), shock (14% vs. 7%; p=.005) or pulse deficit (51% vs. 29%; p=<.001). Arch vessels involvement was more frequent among the stroke pts (68% vs. 37%; p<.001). Stroke pts were treated less frequently by surgery (74% vs. 85%; p<.001). Hospital stay was significantly longer in patients presenting with stroke (median 17.9 versus 13.3 days, p<0.001). Stroke patients demonstrated more frequent in-hospital complications (Table) and higher mortality (adjusted OR 1.62, 95% CI .99-2.65, p=.055) Among hospital survivors, mortality at follow-up was similar in pts with and without stroke (adjusted HR 1.15, 95% CI 0.46-2.89, p=.761).

Conclusions: Stroke occurred in greater than 1 of 20 pts with TA-AAD and was associated with increased morbidity and in-hospital, but not long-term mortality. Whether aggressive early intervention will reduce morbidity and improve mortality remains to be evaluated in future studies.
Abstract 18574: Mitochondrial Reprogramming By Camkiiδ Underlies Gq-induced Cardiomyopathy
Authors: Westenbrink B. Daan , Ling Haiyun , Miyamoto Shigeki , Peterson Kirk , Divakaruni Ajit , Matkovich Scott , Dorn Gerald W , Brown Joan H.
Published: April 2024

Background:
Sustained activation of Gq signaling causes pressure overload hypertrophy, that inevitably decompensates as dilated cardiomyopathy. These molecular processes are recapitulated by cardiac overexpression of Gq (Gq-TG). Ca(2+)/calmodulin-dependent protein kinase II delta (CaMKIIδ) may be a crucial regulator of this maladaptive response and we thus sought to determine if CaMKIIδ is required for the pathologic transformation of cardiac hypertrophy.

Methods:
Gq-TG mice were crossbred with CaMKIIδ knockout (CaMKIIδ-KO) mice to generate KO/TG mice. In addition, we studied the role of CaMKIIδ in the response of neonatal rat ventricular myocytes (NRVM) to constitutively activated Gαq (Ad-Q209L).

Results:
CaMKII activity was increased in hearts from Gαq transgenic mice and in NRVM infected with Ad-Q209L. CaMKIIδ deletion did not affect Gαq-induced hypertrophy in vitro and in vivo, but did result in a significant improvement of left ventricular function and reduced cardiac fibrosis. Deep RNA sequencing revealed marked reprogramming of mitochondrial genes in Gq-TG mice. Intriguingly, 41% of these mitochondrial mRNAs were normalized by CaMKIIδ deletion, including the ROS modulator uncoupling protein 3 (UCP3). Hearts of Gq transgenics showed increased oxidative stress, mitochondrial protein oxidation and a reduced mitochondrial respiration, all of which were normalized in KO/TG mice. The ability of Q209L to induce mitochondrial oxidative stress, mitochondrial membrane depolarization and cell death in NRVMs was also attenuated by CaMKII inhibition. UCP3 protein levels were reduced by Q209L and normalized with CaMKII inhibition. The protective effects of CaMKIIδ-inhibition on mitochondrial ROS production and cell death were abrogated by knock down of UCP3, consistent with a link between CaMKIIδ-induced repression of UCP3 and Gαq-induced ROS production.

Conclusion:
Mitochondrial reprogramming by CaMKIIδ is critically involved in the development of Gq-dependent cardiomyopathy, mediated in part by increased mitochondrial oxidative stress linked to transcriptional repression of UCP3.
Abstract 18589: Virus-Derived Serpin Prolongs Survival and Reduces Vasculitis in Lethal Viral Sepsis in Unrelated Infections
Authors: Chen Hao , Zheng Donghang , Bartee Mee Y , Davids Jennifer A , Lucas Alexandra R
Published: April 2024

Lethal viral infections produce a cytokine storm with disseminated vascular leak, clotting, bleeding, organ failure and high mortality, but treatment remains limited. With this cytokine storm there is a massive influx of inflammatory macrophage and T lymphocytes into the arterial wall and affected organs. Serine proteases in clot-forming and clot-dissolving cascades are regulated by inhibitors termed serpins. Serpins such as anti-thrombin III have been used to reduce DIC and improve outcomes but with limited success. Myxomavirus secretes a potent anti-inflammatory serpin, Serp-1, that inhibits thrombotic factor Xa (fXa) and thrombolytic tissue and urokinase-type plasminogen activators (tPA, uPA). Serp-1 treatment was tested in mouse models of lethal gammaHerpesvirus68 and Ebola virus infections. Serp-1 significantly increased survival in both infections, whereas mammalian neuroserpin, that targets only tPA and uPA, did not. Fator Xa levels were reduced in aortic tissues after Serp-1 treatment. Serp-1 reduced virus load, hemorrhage, inflammation, and organ damage. NSP treatment allowed for a marked suppression of normal spleen cell responses during infections on flow cytometry analysis, while Serp-1 did not. RT-PCR array analysis of aortic sections from infected mice demonstrated significantly altered thrombotic and thrombolytic pathway proteases and serpins as well as addressin gene expression changes with Serp-1 treatment but not with NSP treatment. Treatments with other myxomaviral anti-inflammatory proteins, Serp-2 targeting apoptosis, and M-T7 a chemokine modulator showed trends toward reduced inflammation in the MHV68 infected mice.

Conclusions:
Myxomaviral Serp-1 modulates thrombotic and thrombolytic proteases, markedly improving survival in unrelated lethal viral infections, whereas a mammalian serpin targeting only thrombolysis was ineffective. Treatment targeting both thrombotic and the thrombolytic cascades may improve outcomes in severe viral septic states with vascular inflammation and DIC.
Abstract 186: Baseline ECG Predictors of 90-Day Survival in Wearable Cardioverter-Defibrillator Patients Experiencing a Sudden Cardiac Arrest
Authors: Karia Darshak , Bianco Nicole R , Wan Chingping , Glad Jo Ann M , Szymkiewicz Steven J
Published: April 2024

Purpose: Factors affecting survival after SCA resuscitation continues to be an active area of investigation. The current wearable cardioverter defibrillator (WCD) records ECG periodically. The objective of this study was to determine whether there are any basic ECG differences in patients (pts) that died <90d after first shock versus those that were alive 90d post-shock. We analyzed ECGs at baseline (Base), one week prior to SCA (1WK), and immediately prior to first shock for ventricular tachyarrhythmias VT/VF (pre-S).

Methods: 100 sequential WCD pts (68% male, age 59 ± 16 years) shocked for VT/VF between November 2009 and June 2011 were retrospectively analyzed. Heart rate, QRS duration, QRS amplitude, corrected QT duration (QTc), ectopic activity and rhythm were manually measured at Base, 1WK, and pre-S. The WCD has four non-adhesive ECG electrodes, and measurements were made on both the side-to-side (ss) and front-to-back (fb) leads. Only pts wearing the WCD ≥1 week were included for analysis.

Results: 77 pts survived ≥90 days post shock (68% male, age 58 ± 16 years), and 23 pts died <90 days after first shock (70% male, age 63 ± 13 years). Those pts that died <90 days after first shock had a longer QTc and a shorter QRS amplitude at Base than those surviving ≥90 days post-shock (Table 1)(p≤0.05).

Conclusions: The WCD provides an opportunity to monitor ECG rhythms in at-risk pts prior to defibrillation. Similar to studies of overall mortality, this small study suggests that QT duration and QRS amplitude may be important predictive markers of survival post-SCA.
Abstract 18614: Comparison of the New EuroSCORE II with the Original EuroSCORE and the Society of Thoracic Surgeons Risk Score
Authors: Ad Niv , Henry Linda , Hunt Sharon , holmes Sari
Published: April 2024

Background:
The new EuroSCORE II was developed to improve the prediction risk model of the EuroSCORE I.. In the USA, the Society of Thoracic Surgeons (STS) risk score is more accepted despite being less user friendly and non-applicable to some of the cardiac surgeries. The purpose of this study was to compare the performance of the new EuroSCORE II with the logistic EuroSCORE I and STS mortality predicted risk score .

Methods:
Prospectively collected data from all cardiac surgery patients at a single center with complete data for the three scores (N=9,966) was used. A subabnalysis for patients with cardiac surgeries not accommodated by the STS risk model was performed for comparison of the EuroSCORE II & I (N=4,738). Correlations were conducted between each score and ROC curves were calculated for operative mortality determining the discriminative ability score.

Results:
Our center’s observed operative mortality was 2% -the mean predicted mortality for STS was 2.8%, 3.3% for EuroSCORE II and 7.7% for EuroSCORE I. The discriminative ability of the EuroSCORE II for operative mortality by the area under the curve (AUC) was 0.836, for EuroSCORE I (AUC=0.812) and for the STS score (AUC=0.833). The EuroSCORE II was highly correlated with the EuroSCORE I (
r
=0.83,
p
<0.001) and the STS score (
r
=0.78,
p
<0.001). The EuroSCORE II had a higher correlation with the STS score than the EuroSCORE I (
r
=0.70,
p
<0.001). In the subanalyses comparing the EuroSCORE II vs I, the scores were highly correlated (
r
=0.74,
p
<0.001). For operative mortality (observed=4%), the EuroSCORE II had better discriminative ability (expected=5.6%, AUC=0.749) compared to EuroSCORE I (expected=12.4%, AUC=0.687).

Conclusions:
The new EuroScore II has better operative mortality discrimination compared to the original EuroSCORE, which greatly overestimated the predicted risk of operative mortality. The EuroSCORE II fared well with the STS risk score. Due to the inclusive nature of the EuroSCORE II for multiple procedures, it provides more flexibility than the STS score when dealing with patients undergoing very complex procedures. The EuroSCORE II should be considered when obtaining a risk score for complex cardiac surgical patients.
Abstract 18624: Evidence from an Integrated Analysis Combining Genomics, Transcriptomics, and Lipidomics Implies a Causal Role of Inflammation for Low HDL-C
Authors: Laurila Pirkka-Pekka , Surakka Ida , Sarin Antti-Pekka , Tang Jing , Naukkarinen Jussi , Söderlund Sanni , Ehnholm Christian , Lehtimäki Terho , Eriksson Johan , Salomaa Veikko , Jula Antti , Raitakari Olli , Järvelin Marjo-Riitta , Palotie Aarno , Oresic Matej , Jauhiainen Matti , Taskinen Marja-Riitta , Ripatti Samuli
Published: April 2024

Low HDL-C is a major risk factor for CVD. To elucidate potential novel pathways behind low HDL-C, we have employed 3 different omics: genomics, transcriptomics, and lipidomics.

We performed GWAS on 450 Finns with low or high HDL-C (90th percentiles). Out of 54 individuals, we obtained subcutaneous (SC) fat biopsies for transcriptome analysis, and isolated plasma HDL particles for lipidomics analysis with MS technology.

We first conducted gene network analysis for loci associated with low HDL-C observing that SNPs within 4 inflammatory pathways (e.g. antigen-presentation) were enriched among the low HDL-C associated genes (p=10^-5). Also, these inflammatory pathways were over-expressed in SC fat of low-HDL-subjects (p=10^-10). We then calculated genetic risk scores based on low HDL-C associating SNPs from these pathways, observing that high risk score resulted in both decreased HDL-C-levels and increased expression of these inflammatory pathways. Moreover, individual genes of these pathways (e.g. HLA-DRB1 [p=10^-7, TAP2 p=10^-6) exhibited cis-eQTLs, their expression inversely correlating with HDL-C.

Consistent with this, the inflammatory nature of the HDL particle of low HDL-C subjects was further highlighted by the elevation of proinflammatory ceramides and reduction of anti-oxidative plasmalogens in the lipidomic analysis, which was also genetic risk score dependent.

In a replication analysis of 5 Finnish population cohorts (n=11,211) the low HDL-C associated SNPs were not associated with HDL-C as quantitative trait, but only after using 75, 90, and 95 percentiles as low/high HDL-C criteria. Interestingly, the effect sizes of individual SNPs became stronger when more extreme phenotype criteria for low HDL-C were implemented (e.g. HLA-DRB1; OR for low HDL-C 75 % = 1.11, OR for 90 % = 1.38, OR for 95 % = 1.77).

Our findings imply that genetic variation influences inflammatory processes associated with low HDL-cholesterol on both expression and metabolite levels, suggesting more inflammatory and less vasoprotective role for HDL particles in low-HDL-subjects. Using the extreme phenotype approach, we also demonstrate the presence of ‘low HDL genes’ in addition to the population GWAS identified ‘HDL genes.’
Abstract 18634: Middle School Wellness Program Shows Lasting Impact for Lower Income Community: A Report from Project Healthy Schools
Authors: Corriveau Nicole L , Gurm Roopa , Smith Cydni A , Theurer Allison , Woznicki Elise , Kline-Rogers Eva , Fitzgerald Catherine , DuRussel-Weston Jean , Goldberg Caren , Eagle Kim A , Jackson Elizabeth A
Published: April 2024

Background:
Project Healthy Schools (PHS) is a school based intervention that provides middle-schoolers with in-class learning activities and environmental changes to reduce cardiovascular (CV) and diabetes risks. PHS has 5 main goals: (1) decrease mindless screen time, (2) exercise 150 minutes/week, (3) make better beverage choices, (4) eat more fruits and vegetables and (5) eat less fast and fatty foods. Prior studies have shown positive change among PHS students, and a persistent positive effect through ninth grade in an affluent community; the long-term impact in a lower income community is unknown.

Methods:
Follow up data was collected from 238 sixth grade students in Ypsilanti, a lower income community in Southeast Michigan (median household income $34,685). Data collected included height, weight, lipid levels, blood pressure, heart rate, and a modified SPAN self-evaluation, of healthy eating and other lifestyle behaviors. Data was collect prior to the study, after the study in the sixth grade and annually in the seventh, eighth and ninth grades.

Results
from each consecutive year were evaluated using chi-squared analyses and paired t-tests. Results: After the intervention, students reported an increase in participation in sports teams, a decrease in TV time and playing video games. The students’ physiological measurements total cholesterol, LDL cholesterol (see figure) also improved.

Conclusions:
The follow-up data reflects positive changes in physiological measurements and sedentary behaviors , in the four years following the initial intervention. This suggests that wellness programs such as PHS can be successful in influencing healthy behaviors and reducing long term CV risk, in both affluent and lower income communities.
Abstract 18653: Decreased Levels of Circulating ‰Early Vascular Progenitor Cells are Associated with Cardiovascular Disease Risk
Authors: DeJarnett Natasha K , Conklin Daniel J , Myers John A , Hamzeh Ihab , Wagner Stephen , O'Toole Timothy E , Chugh Atul , Zahn Matthew , Tollerud David J , DeFilippis Andrew P , Higdon Deirdre , Becher Carrie , Wyatt Bradley , Ciszewski Tiffany , Riggs Daniel , McCracken James , Abplanalp Wesley , Prabhu Sumanth D , Bhatnagar Aruni
Published: April 2024

Circulating levels of vascular progenitor cells (VPCs) have been suggested to be reflective of cardiovascular disease (CVD) risk. However, VPCs are a heterogeneous population containing cells with different angiogenic potential, and it is not clear which specific cell types are associated with CVD risk and specific CVD risk factors. We evaluated the relationship between CVD risk factors using antigenically-defined VPC sub-populations with or without validated angiogenic potential. Circulating VPC populations were measured in 240 high risk adults enrolled in the Louisville Healthy Heart Study. To quantify VPC levels, peripheral blood samples were stained with antigenic markers to define 6 different populations and analyzed using flow cytometry. CVD risk data were obtained from questionnaires, medical records, and blood/urine analyses. Generalized linear mixed-effects models were developed to examine the associations between mean VPC levels and the Framingham Risk Score (FRS) and CVD risk factors. A stepwise procedure was used to determine the most parsimonious model. The sample population was 54% male, 51±1 years old, 41% African-American, 39% current smokers, and had a mean FRS of 6±1. Levels of VPC subpopulations, VPC1 (CD31+/34+/45-), VPC3 (CD31+/34+/45-/AC133+), and VPC4 (CD31+/34+/45+/AC133+), significantly predicted FRS (β=-0.13 to -0.25; p=0.04 to 0.006) and showed stronger associations than previous reports using the entire VPC population. VPC2 (CD31+/34+/45+) and VPC6 (CD31+/34+) were not significantly associated with FRS. Moreover, VPC3 levels showed a strong positive association with circulating levels of platelet-leukocyte aggregates (CD41+/CD45+), whereas only the CD31+/AC133+ cells (VPC5) showed a negative association with LDL-C levels. None of the VPC sub-populations were correlated with serum fibrinogen or CRP levels. These observations indicate that immature (“early”) and non-monocytic (CD45-) VPCs levels are indicative of CVD risk and that the depletion of early VPCs (AC133+) may be reflective of a pro-thrombotic state and hypercholesterolemia but not systemic inflammation. Prospective longitudinal studies are required to assess the prognostic utility of measuring VPC subpopulations in peripheral blood.
Abstract 18668: The Clinical Impact of Post Procedural Peripheral Vascular Flow Reserve on Wound Healing Following Infrapopliteal Intervention in Patients with Critical Limb Ischemia
Authors: Fukunaga Masashi , Fujii Kenichi , Kawasaki Daizo , Miki Kojiro , Tamaru Hiroto , Imanaka Takahiro , Shibuya Masahiko , Masutani Motomaru , Ohyanagi Mitsumasa , Masuyama Tohru
Published: April 2024

Background: The impaired coronary blood flow reserve after coronary intervention has been related to microvascular impairment leading to increased morbidity and mortality. We evaluated whether this finding can be generalised to patients with critical limb ischemia (CLI) undergoing endovascular treatment (EVT) for infrapopliteal arterial disease.

Methods: Eleven limbs (Rutherford 4 and 5) from 10 patients of CLI with angiographic evidence of infrapopliteal arterial disease underwent measurement of peripheral vascular flow reserve (VFR). A pressure/temperature sensor-tipped guidewire was positioned in the proximal popliteal artery at 5cm distal to the guiding catheter. With 3 mL of saline at room temperature used as an indicator, by hand-injection, thermodilution curves in the infrapopliteal artery were obtained both at baseline and at intra-arterial papaverine-induced maximum hyperemia (30mg). VFR was calculated from the ratio of inverse mean transit times at hyperemia and baseline. The VFR measurements were performed both before and after EVTs. Wound healing was defined as the progressive reduction in wound surface area from the beginning of the study.

Results: The procedure success rate was 100%, and VFR was measured in all patients without any complication. Wound healing was achieved in 6 limbs after EVT (healing group) and not achieved in 5 (non-healing group). The average pre- and post-VFR was 4.1±2.6 and 5.8±4.2 respectively. There was no significant difference in pre-VFR values between healing and non-healing group (4.3±3.2 versus 3.7±2.0). However, post-VFR values was significantly higher in the healing group than in the non-healing group (6.3±4.1 versus 3.3±1.8, p<0.05). VFR values in non-healing group decreased or remained unchanged in all patients mainly due to increase in resting blood flow.

Conclusions: VFR values immediately after EVT for infrapopliteal arterial disease remained unchanged in patients with poor wound healing mainly due to increase in resting blood flow. This finding suggests that a therapeutic effect can not be obtained if the arteriolar bed is damaged after EVT. This easily assessable VFR is useful in clinical risk stratification for patients with CLI immediately after EVT in the catheterization laboratory.
Abstract 18679: Stand Alone Cox-Maze Procedure for Patients with Non Paroxysmal Atrial Fibrillation- A Single Center Experience
Authors: Ad Niv , Henry Linda , Hunt Sharon , Freihling Ted , Wish Marc , Holmes Sari
Published: April 2024

Background: Catheter ablation for atrial fibrillation (AF) performed percutaneousely or using minimally invasive (MI) off bypass surgical techniques is shown to be limited in patients with non-paroxysmal AF (non PAF). The Cox-Maze procedure (CM) on bypass is effective in non-PAF patients, but concerns about associated morbidity were raised. The study purpose assesses the safety and efficacy of a stand alone on pump CM procedure in patients with non-PAF.

Methods: Since 2005, 690 patients had surgical ablation at our institution: 175 (25%) referred for stand alone CM procedure; 138 (20%) undergoing a stand alone procedure for non-PAF . All patients are followed prospectively thru our AF registry. Rhythm verified by EKG and 24-hour holter using the Heart Rhythm Society definition of failure. Health-related quality of life (HRQL, SF-12) and AF symptoms assessed preoperatively/12 months post procedure.

Results: Mean age of: 56.9±8.7 years; 60% had at least 1 prior cardioversion and 42% had a catheter ablation; other descriptives and major perioperative morbidities table. The return to sinus rhythm at 6, 12 and 24 months and off antiarrythmic drugs respectively are: 93%/83%; 93%/85%; 90%/79%. In a multivariate analysis, duration of AF predicted rhythm 12 months after surgery, with 20% greater odds of AF at 12 months for each year increase in duration (OR=1.20, CI: 1.03-1.40) after adjustment for other risk factors. By 2 years, only 20% of patients remained on Coumadin with only1 embolic stroke in 44±26 patient months. HRQL significantly improved (p<0.001) and symptoms significantly decreased (p=0.003) by 12 months. By Kaplan-Meier analysis - 97.6% cumulative survival (CI: 95-100%) at 2 years.

Conclusion: On pump stand alone CM procedure can be performed with comparable morbidity to catheter ablation. Long term success in non-PAF patients with large left atria is promising. Our experience suggests development of educational strategies to overcome an initial learning curve.
Abstract 18692: High Flavanol Dark Chocolate Reduces NT-proBNP in Patients with Chronic Heart Failure
Authors: de Palma Rodney , Sotto Imelda , Khan Noorafza Q , Wood Elizabeth G , Butler Jane , Johnston Atholl , Rothman Martin T , Corder Roger
Published: April 2024

Background:
Endothelial dysfunction in patients with heart failure (HF) has been linked to a worse prognosis. High flavanol cocoa products improve endothelial function, but it has yet to be established whether such changes are sufficient to confer medical benefit. We investigated whether high flavanol dark chocolate (HFDC) reduces the severity of HF by measuring changes in amino-terminal pro-B type natriuretic peptide (NT-proBNP).

Methods:
Patients with HF and a history of ischemic heart disease (n = 32), stable on optimal medication according to standard guidelines, were randomized to consume 50 g per day of either HFDC or low flavanol dark chocolate (LFDC) for 4 weeks, and then crossed over to consume the alternative dark chocolate for a further 4 week. The flavanol contents of the HFDC and LFDC were 1094 and 95 mg/50 g. NT-proBNP, blood pressure, and aortic pulse waveform derived from radial artery applanation tonometry were assessed at baseline, after each 4-week treatment phase, and at follow-up 4 weeks after completion of chocolate consumption.

Results:
24 subjects completed the study. After 4 weeks consumption of HFDC, NT-proBNP was significantly lower compared to baseline (P = 0.016), LFDC (P = 0.019) and at follow-up (P = 0.004). After HFDC, diastolic blood pressure (DBP) was decreased compared to LFDC (mean decrease ± SD; -7 ± 10 mmHg, P = 0.003 and compared to baseline measurements (-4 ± 9 mmHg, P = 0.047). Figure 1 shows a comparison of mean changes in DBP and NT-proBNP after HFDC compared to baseline, LFDC and follow-up values. Mean decrease in NT-proBNP was >30% in 12 patients.

Conclusions:
Reductions in NT-proBNP and blood pressure after HFDC are consistent with a decrease in vascular resistance resulting in reduced left ventricular afterload. Post treatment reductions of NT-proBNP >30% have previously been associated with improved outcome in patients with HF. Hence, long-term benefits of high flavanol interventions in HF merit further investigation.
Abstract 187: U/T Wave Amplitude Ratio as an Indicator of Ventricular Arrhythmia Risk After Myocardial Infarction
Authors: Wang Bei , Korhonen Petri , Väänänen Heikki , Toivonen Lauri
Published: April 2024

Objectives:
This prospective study examined if abnormal repolarization presenting as increased U/T wave amplitude ratio predicts ventricular arrhythmias in patients with a recent myocardial infarction (MI) and moderate cardiac dysfunction.

Methods and results:
The study group (n = 126, 24 female) comprised patients with a recent MI and left ventricular ejection fraction (LVEF) < 50%. Mean age was 60 years and LVEF 40%. A 120-channel body surface potential mapping (BSPM) registration was performed at hospital discharge. After signal-averaging of 250-300 beats, T- and U waves were identified and their amplitudes computed with a custom made software. QRS duration was computed for comparison. The study endpoints were arrhythmic events (sudden cardiac death, sustained ventricular tachycardia or ventricular fibrillation), cardiac mortality, and all-cause mortality. During a mean follow-up of 51 months 22 patients (17.3%) died with 13 (10.3%) suffering cardiac death. Twelve patients (9.5%) had an arrhythmic event. Patients with arrhythmic event had significantly higher U/T maximum amplitude ratios (the ratio between the highest U and T waves in BSPM) compared to those without (0.222 ± 0.129 vs. 0.129 ± 0.085, p = 0.012). U/T maximum amplitude ratio was a significant predictor of arrhythmic events (log-rank 9.3, p = 0.002) and in multivariate analysis it showed predictive power independently of clinical variables including age, sex, LVEF, bundle branch block, and diabetes with the hazard ratio (HR) of 5.84. QRS duration also showed prediction with the HR of 1.04. A combination of the parameters further improved prediction with an area under the ROC curve of 0.80 ± 0.07 (p < 0.001). U/T maximum amplitude ratio did not predict cardiac or all-cause mortality.

Conclusion:
U/T wave amplitude ratio is a marker of ventricular arrhythmia propensity after MI. A combination of parameters describing repolarization and depolarization abnormalities further improves ventricular arrhythmia risk assessment.
Abstract 18734: KLF4 Regulates Aortic Aneurysm Morphology and Deletion Attenuates Aortic Aneurysm Formation
Authors: Salmon Morgan , Johnston William F , Su Gang , Upchurch Gilbert R , Owens Gary K , Ailawadi Gorav
Published: April 2024

Objective: Kruppel-like Factor 4 (KLF4) is known to play a role in inducing phenotypic modulation of smooth muscle cells (SMC) following ischemia reperfusion injury and in atherosclerosis; however, its role in aortic aneurysms (AA) remains unknown. The study objective was to evaluate the role of genetic deletion of KLF4 on development of experimental AAs.

Methods: 8-12 week male (n=12) KLF4 flx/wt ERT tamoxifen Cre+ mice (“KLF4 conditional het KO mice”) and KLF4 flx/wt ERT tamoxifen Cre- (WT) mice underwent elastase perfusion following tamoxifen injection. In separate experiments, 8-12 week male (n=13) KLF4 flx/flx Smooth muscle myosin heavy chain (Myh11) Cre+(“SMC specific conditional KLF4 KO mice”), and KLF4 wt/wt SM-MHC Cre+ (“Myh11 Cre WT”) underwent elastase perfusion following tamoxifen administration. At 14 days, maximal aortic dilation was measured with video micrometry. Aortic samples were evaluated with histology for α-actin, macrophages, neutrophils, T lymphocytes and elastin.

Results: Maximal aortic dilation was significantly reduced in KLF4 conditional het KO mice compared to WT controls (42.9 ± 7.3% versus 78.9 ± 12.6%, p<0.039). In addition, these mice had reduced macrophage and neutrophil infiltration with greater elastin preservation and α-actin expression. SMC specific conditional KLF4 KO mice also showed a significant reduction in aortic dilation following elastase perfusion as compared to Myh11 Cre+ WT controls (53.4 ± 7.76% versus 93.8 ± 16.2%, p<0.028). These mice also had reduced macrophage and neutrophil staining and increased elastin preservation and α-actin expression.

Conclusions: KLF4 plays a critical role in promoting AA formation, since heterozygous KLF4 KO mice showed reduced aneurysm formation. At least part of this effect is due to loss of KLF4 in SMC since SMC specific conditional KLF4 KO mice also showed reduced AA formation as well as decreased immune cell recruitment and greater preservation of elastin and SMCs. Taken together, results identify KLF4 as a novel therapeutic target for treatment of aneurysms.
Abstract 18738: The Cdkn2a/2b Tumour Suppressor Locus is a Hot Spot for Genome Instability in Mouse Cardiac Progenitor Cells
Authors: Noseda Michela , De Smith Adam J , Leja Thomas , Rao Pulivarthi H , Abreu paiva Marta S , Al-Beidh Farah , Blakemore Alex I , Schneider Michael D
Published: April 2024

Among the cells with best cardiac potential, autologous heart cells present the fewest regulatory issues, and therapeutic trials are on-going. Existing work has largely relied on purified but potentially heterogeneous populations. As ES, iPS and cardiosphere-derived cells all are known to accumulate genomic aberrations, we analyzed genome integrity in clonally derived mouse Lin-/Sca-1+/side population (SP) cardiac progenitor cells (CPCs), which stably express cardiogenic transcription factors for ≥ 35 passages. DNA content analysis showed progressive aneuploidy, with >90% of clones abnormal by passage 11. By multicolour spectral karyotyping (SKY), even those with normal DNA content had aberrations, though no recurrent anomalies were seen; genome instability was not contingent on clonal isolation per se or Hoechst 33342. High-resolution array CGH (aCGH) was performed on 15 clones, using 1 million probe arrays. Numerous aberrations were found, most 100-fold below the limits of SKY. Interestingly, copy number variation did not explain the observed differences in cardiac transcription factors. After passage 10, recurrent deletions were seen in Cdkn2a/2b, encoding the tumour suppressors p16Ink4a, p15Ink4b, and p19ARF. QPCR confirmed this in >80% of clones. Integrity of Cdkn2a/2b through passage 10 indicates its deletion is not required for clonal growth. Because genome instability has been ascribed to hyperoxic stress in ambient (21%) [O2], we derived and propagated clones in physiological (2 or 7%) [O2]. Reduced [O2] increased (>3x) and accelerated (2x) clone formation, reduced aneuplody, reduced chromosomal aberrations, but did not prevent loss of Cdkn2a/2b. Low [O2] also enabled generating clones readily from Lin-/Sca1+/SP- CPCs, for which the cloning efficiency was previously reported as < 0.1%. Thus, genomic instability of propagated CPCs was demonstrated, including recurrent deletion of Cdkn2a/2b. Reduced [O2] conferred partial protection from genomic instability. Clonal analysis unveiled heterogeneities in genome structure that could be obscured in a mixed population. These data highlight the need to develop bioprocesses that optimize genomic stability.
Abstract 18744: Peripheral Blood Gene Expression Reflects Differences Between Coronary Artery Calcification and Stenosis as Assessed by Coronary Artery Calcium Scanning and Ct Angiogaphy
Authors: Voros Szilard , Budoff Matthew J , Kraus William , Thomas Gregory , Elashoff Michael , Wingrove James , Rosenberg Steven
Published: April 2024

Background.
We previously validated a composite peripheral blood gene expression score (GES) based on age, sex and 23 genes to detect obstructive coronary artery disease (CAD), using invasive coronary angiography as gold standard (≥50% diameter stenosis). Plaque and stenosis can also be assessed by cardiovascular CT.

Methods.
614 symptomatic patients with no known CAD or diabetes from the COMPASS and PREDICT studies underwent CAC and CTA by institutional protocols and GES was measured according to Corus® CAD protocols in the CardioDx CLIA laboratory (Palo Alto, CA). CAC was expressed as Agatston score. For qualitative analysis, each of the 17 segments was graded for stenosis as 0: none, 1: minimal, 2: mild, 3: moderate and 4: severe; segment involvement score (SIS) was calculated by adding all segments with any plaque and segment stenosis score (SSS) by summing individual segment scores. Patients from COMPASS (N=394) also underwent quantitative measurements of calcified, high-density and low-density non-calcified plaque, as previously described. Expression levels of the 23 genes were analyzed by age and sex-adjusted logistic regression.

Results.
In the 614 patients, mean age was 57±10; 50% were men. Overall GES was significantly correlated with CAC (r=0.35) and MPS (r=0.41), both p<0.001. Individual gene expression level analysis showed that genes from the myeloid lineage, including S100A12/8, were significantly increased and T cell genes decreased with increasing MPS, whereas only innate immunity (myeloid and NK, S100A12/8, SLAMF7) genes were significantly increased with increasing calcification. In the quantitative analysis set (N=394, mean age: 55±12, 50% men) a similar pattern was observed with only neutrophil genes significantly upregulated with calcification, whereas both B and T cell genes were downregulated with increasing MPS.

Conclusions.
Gene expression and qualitative and quantitative cardiac CT data showed that peripheral blood gene expression changes for overall maximum percent stenosis and calcification differ. MPS was associated with increased expression of innate immune genes and decreased lymphocyte gene expression, while calcification was associated with increases in innate immune gene expression.
Abstract 18753: ST Elevation Myocardial Infarction in Hospitalized Patients is Associated with Delayed Recognition, Low Rate of Early Revascularization and High Mortality
Authors: Dai Xuming , Bumgarner Joseph , Spangler Andrew , Smith Sidney , Stouffer George A
Published: April 2024

Background ----
Efforts to improve the management of ST segment elevation myocardial infarction (STEMI) have focused on patients whose symptoms begin outside of the hospital. Relatively little is known about STEMI that occurs in patients hospitalized for another condition.

Methods ----
In-patient STEMI at a university hospital with primary percutaneous coronary intervention (PCI) center were identified by searching the Discharge Database and Cardiac Catheterization Laboratory Database. The diagnosis of STEMI was confirmed by two cardiologists. Non-normally distributed data are presented as median [25%,75%]. Comparison between groups was done using Mann-Whitney rank sum test for continuous variables and χ
2
for categorical variables.

Results -
A total of 48 in-patient STEMI cases were identified from 139,410 adult discharges from 2007 to 2011. In comparison with 184 out-patient STEMIs who presented directly to the same hospital during the same time span, in-patient STEMI patients were older (69 ± 13 vs 60 ± 13 years; p < 0.01) and more often female (50% vs 33%; p < 0.01). Symptoms were the reason for the index ECG more often in outpatient STEMIs (99% vs 33%; p < 0.01); for in-patient STEMIs a change in clinical status (60%) and/or changes on telemetry (7%) also precipitated an ECG. The median time between the onset of symptoms or change in clinical status to ECG for in-patient STEMI was much greater than door to ECG time for outpatient STEMI (30 [10, 600] vs 5 [2, 10] minutes; p < 0.001). Coronary angiography (71% vs 97%; p < 0.01) and PCI (56% vs 95%; p < 0.01) were performed less frequently in in-patient STEMI. The median ECG to angiography time (91 [45,197] vs. 34 [24,47] minutes; p < 0.001) and the ECG to first device activation (129 [65,250] vs. 51 [40,70] minutes; p < 0.001) were longer with in-patient STEMI. The in-hospital mortality for the in-patient STEMI group was 39.6% but revascularization within 3 hours from the onset of STEMI related event was associated with lower in-hospital mortality compared to patients who had delayed or no revascularization (15% vs 50%; p = 0.02).

Conclusion ----
In-hospital STEMI is associated with atypical clinical presentation, delayed ECG interpretation, low rate of rapid revascularization and high mortality.
Abstract 18765: PAR-1 Contributes to the Innate Immune Response to Viral Infection
Authors: Antoniak Silvio , Owens Albert P , Williams Julie C , Lee Rebecca D , Weithäuser Alice , Baunacke Martin , Sheridan Patricia A , Malz Ronny , Pawlinski Rafal , Blaxall Burns , Beck Melinda A , Rauch Ursula , Mackman Nigel
Published: April 2024

Objective:
Viral infections activate the blood coagulation cascade as part of the host defense response. Coagulation proteases, such as thrombin, induce cellular responses by cleaving protease-activated receptors (PARs). It has been proposed that infections are detected by a dual-sensor system consisting of PARs and Toll-like receptors (TLRs). In this study, we analyzed the role of PAR-1 in host defense against infection with coxsackievirus B3 (CVB3) and influenza A virus.

Methods:
Wild-type (WT) and PAR-1 deficient (PAR-1
-/-
) mice were infected with either CVB3 or influenza A (H1N1/PR8). The innate immune response, viral load and inflammation were was analyzed. Bone-marrow transplantation experiments were performed to identify the cellular source of PAR-1 contributing to the innate immune response to CVB3. In addition, we analyzed the effect of PAR-1 activation on TLR3-dependent induction of interferon-β and CXCL10 expression in culture cardiac fibroblasts.

Results:
PAR-1
-/-
mice exhibited a reduced innate immune response to both viral infections that led to higher viral titers and inflammation compared to WT mice. PAR-1
-/-
mice also exhibited increased CVB3-induced myocarditis. Bone marrow transplantation experiments demonstrated that PAR-1 on non-hematopoietic cells played a role in CVB3 infection, and mice overexpressing PAR-1 on cardiomyocytes had reduced myocarditis. Stimulation of PAR-1 on mouse cardiac fibroblasts enhanced p38 activation and TLR3-dependent induction of interferon-β and CXCL10.

Conclusion:
Our results indicate that activation of PAR-1 contributes in a p38-dependent manner to the innate immune response to viral infection. The use of PAR-1 inhibitors to reduce platelet activation in patients with cardiovascular disease may increase their susceptibility to virus infections.