bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 17332: Are Current Electrocardiographic Criteria For Detecting LVH Relevant in African Americans? Evidence From the Jackson Heart Study
Authors: Fugate Thomas C , Guido Joseph , Taylor Herman , Pearson Thomas
Published: April 2024

Left Ventricular Hypertrophy (LVH) is a major risk factor for cardiac arrhythmias, heart failure, and sudden death. The current gold standard for detecting LVH is echocardiography, but individuals can be first screened using a resting electrocardiogram (ECG). The current algorithm for detecting LVH by ECG is derived from the nearly all-Caucasian Framingham Heart Study (FHS).The use of Framingham ECG criteria to predict LVH in African Americans (AA) has not been validated. We tested whether Framingham ECG criteria used to detect LVH performed as well in AA. The Jackson Heart Study is a population-based study of AA, consisting of 1941 men and 3360 women. Linear regression analysis of five different ECG LVH criteria proposed in FHS, correlated left ventricular mass (LVM) on M-mode echocardiogram with ECG voltage before and after adjusting for BMI and age. Limb and chest leads voltages in JHS men and women, in comparison to the FHS men and women, showed S wave leads in V3, V4, in men, and V2 and V3 in women have the strongest correlation to LVM (P value< .0001). Among the limb leads, the JHS results were similar to the Framingham cohort, showing RI, SIII and RAVL most strongly associated with LVM in both sexes (P value<.0001). Sensitivity was calculated for five ECG criteria before and after adjusting for BMI and age using the definition of LVH as 2SD above the height- adjusted, sex specific JHS mean (95% specificity). Two of the ECG criteria, RAVL+SV3 and (RAVL+SV3)x QRS duration, in both men and women, had significantly greater sensitivities before and after adjusting than their FHS counterparts. JHS data identified ECG criteria (RAVL+SV3)x QRS duration to have the greatest sensitivity in both sexes unadjusted and adjusted for BMI and age (males 28.3% unadjusted, 71.4% adjusted; females 29.4% unadjusted and 60.3% adjusted). The data suggest that current criteria used to define LVH in a Caucasian population, (RAVL+SV3)x QRS duration, is at least as sensitive at the same level of specificity in African American populations and perhaps more so. These data support the utility of current LVH criteria for use in LVH screening in African American men and women.
Abstract 17386: The Survival Impact of Genetic and Chromosomal Aberrations, Non-Cardiac Congenital Defects and Acquired Baseline Morbidity on Neonates with Congenital Heart Disease. How Does the “Perfect” Child Fare?
Authors: Hickey Edward J , Nosikova Yaroslavna , Caldarone Christopher A , Redington Andrew , Van Arsdell Glen S
Published: April 2024

Background
Genetic aberrations, congenital non-cardiac defects and baseline acquired co-morbidities greatly hamper counseling, prognostication and decision-management for neonates with congenital heart defects. We aimed to define the relative risks of these factors.

Methods
Over 10 years, we have admitted 1618 neonates <30 days with congenital heart defects. For all 1618, consults throughout follow-up were reviewed including genetic consults (318), FISH results (246), cardiology clinics and in-patient progress. Outcomes were analyzed via parametric modeling with multivariate risk-adjusted regression. All risk factors were tested for reliability through bootstrap bagging (N=1000).

Results
Genetic defects were confirmed in 180 (11%). Aberrations included duplications (98; T21=56, T18=21, T10=13), Ch22 defects (47), Turner (4) and specific gene mutations. An additional 180 (11%) had defined clinical syndromes or congenital non-cardiac defects. Acquired non-cardiac co-morbidity at time of presentation was present in 244 (15%) (CNS=11; Resp=69; GIT=55; Renal=30; Sepsis=70), 144 of whom also had genetic defects. “Perfect” patients - lacking genetic, syndromic or acquired co-morbidites - comprised 1118 (69%). Comfort care was offered to 61 (Perfect=11; T18=21; T13=8; T21=1; Acquired=2). The actively managed 1557 showed late survival >90% for the “perfect” patient. Genetic defects/syndromes and acquired co-morbidity strongly affected survival (figure). However in risk-adjusted analyses, chromosomal/gene defects were overshadowed by acquired morbidity or congenital defects affecting specific systems (table; CNS, Respiratory).

Conclusions
The “perfect” neonate with congenital hearts disease has an excellent prognosis. However, chromosomal/genetic aberrations do not necessarily imply poor outcome. Instead, acquired non-cardiac morbidity at time of presentation are stronger determinants of outcome.
Abstract 17402: Sleep Apnea Predicts the Extent of Myocardial Damage After Acute Myocardial Infarction Determined by Cardiovascular Magnetic Resonance Imaging
Authors: Buchner Stefan , Satzl Anna , Debl Kurt , Luchner Andreas , Hamer Okka W , Poschenrieder Florian , Obermeier Ruth , Pfeiffer Michael , Novak-Brandl Astrid , Braune Astrid , Riegger Günter , Arzt Michael
Published: April 2024

Background:
In patients with acute myocardial infarction (AMI) sleep apnea (SA) exposes the heart to repetitive oxygen desaturations and increased cardiac afterload. The relation between SA and the extent of myocardial infarct size has not been studied yet. The objective of this clinical evaluation was to test the hypothesis that SA is among known risk factors associated with larger infarct size in AMI patients, using cardiovascular magnetic resonance (CMR).

Methods:
We studied 24 patients with AMI who were successfully treated with percutaneous coronary intervention. All patients underwent polysomnography and delayed contrast-enhanced CMR was performed to define myocardial scar. Patients were stratified into two groups according to the infarct size. A large infarct size 3 months after AMI was defined as ≥24g assessed by CMR. To determine predictors of large infarct size we used multivariate logistic regression analysis.

Results:
Overall, the mean infarct size was 23±12 g. The mean AHI was significantly higher in the greater infarct size group compared to the smaller infarct size group (37±8/hour vs 16±8/hour, p=0.02). Multivariate analysis including age, gender and time-to-reperfusion revealed that AHI was an independent risk factor (p=0.034) for greater infarct size (≥24 g).

Conclusion:
In addition to late or insufficient revascularisation SA predicts the development of a large myocardial scar three months after myocardial infarction.
Abstract 17496: IL2 Soluble Receptor and Neopterin Levels in Peripartum Cardiomyopathy and Recent Onset Cardiomyopathy in Non-Peripartum Women and Men
Authors: McNamara Dennis M , Hanley-Yanez Karen , Cooper Leslie , Sheppard Richard , Pauly Daniel , Narula Jagat , Pisarcik Jessica , McTiernan Charles ,   for the IMAC Investigators
Published: April 2024

Introduction:
IL2 soluble receptor (IL2Rs) and neopterin (NPT) are peripheral markers of T cell and monocyte activation investigated extensively in auto-immune disorders. We assessed these biomarkers in subjects with non ischemic cardiomyopathy of recent onset (ROCM) from the IMAC2 (Intervention in Myocarditis and Acute Cardiomyopathy) registry. We compared the degree of cellular activation in peripartum cardiomyopathy (PPCM) with that evident in non-peripartum women and men with ROCM.

Methods:
130 subjects were investigated: 96 subjects with ROCM including 37 women with PPCM (group 3), 27 non-peripartum women (group 2) and 32 men (group 1), and 34 controls without cardiac disease (CTL). All subjects with ROCM had serum obtained at entry and an assessment of LVEF by transthoracic echocardiography. LVEF was reassessed 6 months after enrollment.

Results:
The ROCM cohort (n=96, 64F/32M, mean age 30±6) had a mean LVEF at baseline of 0.24±0.08 which increased to 0.43±0.13 at 6 months. For controls (mean age 45±6, 24F/10M) the mean LVEF was 0.58±0.10. Both IL2Rs and NPT were markedly elevated in ROCM subjects compared to controls (IL2Rs: ROCM=1411±671, CTL=970±329 pg/ml, p<0.001; NPT: ROCM=9.2±5.6, CTL=6.2±3.1 nmol/l, p=0.003). Increased NYHA class was associated with higher serum levels for both NPT (p=0.013) and IL2Rs (p=0.009). No differences were evident in subjects with PPCM versus men and women with ROCM for either IL2Rs (group 1/2/3 =1524±504/1531±904/1225±566 pg/ml, p=0.10) or NPT (group 1/2/3=9.4±6.5 /9.3±5.8 /8.9±4.7 nmol/l, p=0.92). IL2Rs levels were lower in black subjects: blacks (n=25) IL2Rs=1123±496; whites (n=71) 1513±698, p=0.012. Levels of IL2Rs and NPT did not predict the degree of recovery at 6 months, although there was a nonsignificant trend towards more recovery with lower IL2Rs levels.

Conclusions:
Marked elevation of IL2Rs and NPT, biomarkers of cellular immune activation, are evident in subjects with ROMC. The degree of activation in subjects with PPCM appears similar to that seen in men and non-peripartum women with ROCM, suggesting similar inflammatory pathogenesis for these syndromes of acute heart failure. The relationship of cellular activation to myocardial injury and recovery in ROCM should be further investigated.
Abstract 17497: Ischemic Grade on the Admission ECG of a First St-Elevation Myocardial Infarction Predicts Microvascular Damage and Impaired Functional Recovery
Authors: Timmermans Philippe , Bogaert Jan , Dymarkowski Steven , Adriaenssens Tom , Coosemans Mark , Dubois Christophe , Ferdinande Bert , Sinnaeve Peter , Belmans Ann , Voigt Jens-Uwe , Desmet Walter , Janssens Stefan
Published: April 2024

Background:
Prediction of recovery of systolic function after STEMI remains challenging. Microvascular obstruction (MVO) is a known predictor of negative remodeling after reperfusion therapy, but can only be diagnosed on cardiovascular magnetic resonance (CMR). We sought to evaluate the relationship between ischemic grade on the presentation ECG on MVO severity at baseline and functional recovery after 4 months.

Methods:
We prospectively enrolled 134 patients with a first STEMI undergoing successful PCI followed by state-of-the-art postinfarction medical treatment, and quantified MVO at day 3-4, and LV functional and structural remodeling after 4 mo follow-up using 1.5 T CMR and TTE. Ischemic grade was defined as ST elevation with distortion of the terminal portion of the QRS on ECG. Grade 2 and 3 ischemia represented the ST J amplitude greater or smaller than 50% criterion or presence or absence of an S wave or any Q in V2 and V3.

Results:
Patients with grade 2 (n=77) and 3 (n=57) ischemia had comparable pre- and peri-procedural medication and cardiovascular risk profiles, except for age. Patients with gr 3 ischemia were older than those with gr 2 (60±12 vs 57±11y, P<0.05), had a longer delay between symptom onset and PCI (4.7±2.7 vs 4.1±3.1 hours, P<0.05) and a trend for a greater proportion of TIMI 0 flow before PCI (p=0.058). Infarct-related artery and TIMI flow after PCI were similar. Troponin and CK levels at admission were similar, but significantly higher after 24 h in patients with gr 3 ischemia (P<0.001). Patients with gr 3 ischemia had significantly more MVO (4±6 vs 10±13 g, P<0.01), greater area at risk (44±23 vs 34±20 g, P<0.01) and larger infarct volumes both at baseline and at 4 mo (23±14 vs 14±10%LV mass and 15±13 vs 11±7% respectively, P<0,001 for both), and smaller myocardial salvage index (p<0.003). LVEF at admission and after 4 mo measured by TTE was lower in gr 3 ischemia (52±12 vs 54±11, P<0.01 and 53±11 vs 61±9, P<0.001). Serial CMR confirmed impaired global LV systolic function recovery in patients with gr 3 ischemia (P<0.001).

Conclusion:
Gr 3 ischemia in STEMI is a valuable predictor of extensive myocardial microvascular damage on CMR imaging, and is closely associated with impaired functional and structural recovery after successful PCI for STEMI.
Abstract 17546: No Decrease in the Incidence of Heart Failure Following Acute Myocardial Infarction in the Years 1994-2006
Authors: Kostis William J , Deng Yingzi , Moreyra Abel E , Pantazopoulos John S , Kostis John B ,   For the Myocardial Infarction Data Acquisition System (MIDAS) Study Group
Published: April 2024

Objectives:
Heart failure (HF) is a common serious complication following acute myocardial infarction (MI). We studied whether improvements in MI treatment had an impact on the incidence of post-MI HF.

Methods:
We used data from the Myocardial Infarction Data Acquisition System (MIDAS) database, selecting all first myocardial infarctions admitted to non-federal hospitals in the state of New Jersey between 1994 and 2006. We studied the incidence of HF during admission, within 28 days of admission, and 28 days to one year from admission. Using a multivariate model, we assessed which clinical characteristics had an impact on the incidence of HF.

Results:
A total of 185,483 patients were admitted with a first MI. The incidence of HF within one year was 38.2% in 1994 and remained stable through 2006 (range 37.6% - 41.0%). The incidence of HF in patients with subendocardial MI was also stable and significantly higher than that observed in transmural MI (43.7% vs. 30.9%, p<0.0001). However, among patients with transmural MI, HF incidence within one year declined from 32.8% in 1994 to 26.3% in 2006 (p<0.0001), mainly due to a decline in HF during the index admission. HF incidence after discharge remained stable in transmural MI and increased in subendocardial MI. By multivariate modeling, older age, female gender, black race, diabetes, atrial fibrillation, renal disease, and chronic obstructive pulmonary disease were associated with higher incidence of HF (p<0.0001 for all). Patient age and the rates of diabetes, hypertension, renal disease, cancer, and anemia increased during the period of observation (p<0.0001).

Conclusions:
Despite major advances in management of acute myocardial MI, the incidence of post-MI HF remained stable. The only decline observed was in HF during an index admission for transmural MI. Subendocardial MI was associated with a higher HF incidence. These findings may be due to the increasing age and rates of comborbidities among patients with first MI.
Abstract 17567: Stanniocalcin-1 Induces A Novel Anti-Oxidant Pathway in Cardiomyocytes
Authors: Wang Yanlin , Liu Dajun , Huang Luping , Wang Wei , Wehrens Xander H , Belousova Tatiana , Abdelrahim Maen , DiMattia Gabriel , Sheikh-Hamad David
Published: April 2024

Rationale:
We have shown increased cardiac stanniocalcin-1 (STC1) in patients with idiopathic dilated cardiomyopathy. STC1 localizes to the inner mitochondrial, and transgenic overexpression of STC1 is associated with increased energy utilization.

Objective:
We examined the hypothesis that STC1 uncouples mitochondrial oxidative phosphorylation - to affect energy metabolism and superoxide generation in cardiomyocytes.

Methods and Results:
Compared to WT mouse heart, STC1 Tg heart displays 2-fold higher uncoupling protein 3 (UCP3) levels, 40% lower ATP levels, but similar activities of respiratory chain complexes I-IV. In cultured adult rat cardiomyocytes, recombinant hSTC1 is internalized by cultured rat cardiomyocytes and is targeted to the mitochondria within minutes; it induces UCP3, decreases mitochondrial membrane potential and suppresses baseline and ANG II-provoked superoxide generation. In freshly-isolated adult mouse cardiomyocytes, STC1 diminishes baseline and ANG II-induced superoxide generation equally in WT and gp91
phox
-/-
cardiomyocytes, suggesting gp91phox-independent mechanism of action. Baseline superoxide generation is higher in freshly-isolated adult UCP3
-/-
mouse cardiomyocytes, compared to WT; and, treatment of UCP3
-/-
cardiomyocytes with STC1 failed to suppress superoxide generation in the presence or absence of ANG II, suggesting that the effects of STC1 on superoxide generation are UCP3-mediated.

Conclusion:
STC1 activates a novel anti-oxidant pathway in cardiac myocytes through induction of UCP3; this pathway may play an important role in regulating reactive oxygen species in the heart under normal physiologic and pathophysiologic conditions, and ameliorate the deleterious effects of ANG II-mediated cardiac injury.
Abstract 17607: Substrate Based Atrial Fibrillation Ablation Guided by Voltage Gradient Mapping: Initial Results and Near-Term Clinical Outcome
Authors: Bailin Steven , Hoffman Craig , West Robert
Published: April 2024

Background:
Ablation of atrial fibrillation (AF) is anatomic based with isolation of pulmonary veins (PVs), generally in combination with linear ablation. Because AF is chaotic, activation mapping cannot reveal underlying mechanisms or reasons for success or failure. We report substrate based ablation guided by voltage gradient mapping (VGM) provides promising initial and near-term success.

Methods and Results:
55 consecutive patients undergoing AF ablation, 29 paroxysmal (PAF) and 26 chronic (CAF), had contact voltage mapping within the left and right atrium, PVs, SVC, and IVC. Adjustment of voltage levels displayed low voltage connections between higher voltage regions. Ablation of low voltage bridges (LVB) was performed until repeat maps had no demonstrable LVB. Ablation endpoints were termination of AF and failure to induce AF or tachycardia. Clinical success was defined by the absence of recurrent AF (primary endpoint), and freedom from sustained arrhythmias (secondary endpoint) documented by 30 day monitoring 4 months following ablation. LVB ablation resulted in AF termination in 43/46 patients (93%) and AF was not inducible in 52/55 (95%). Single procedure success for prevention of recurrent AF was 51/55 (93%) and freedom from atrial arrhythmia was 39/55 (71%) (PAF: 86%; CAF: 56%). Following a second procedure the arrhythmia free success was 49/55 (89%); PAF: 97%; CAF: 81%.

Conclusions:
We conclude that VGM of atrial substrate is an effective tool to guide ablation therapy. This method provides a high single procedure success in both PAF and CAF achieving the primary endpoint in 95% and secondary endpoint of 71%.
Abstract 17732: Combination of B-Type Natriuretic Peptide and Minute Ventilation Carbon Dioxide Production Slope Improves Risk Stratification in Patients with Diastolic Heart Failure
Authors: Yan Jing , Li Li , Gong Shi-jin , Dai Hai-wen , Chen Jin , Yu Yi-hua , Xv Qiang-hong , Cai Guo-long
Published: April 2024

Objectives
To investigate the prognostic values of the minute ventilation/carbon dioxide production slope (VE/VCO
2
) and peak oxygen consumption (VO
2
) for cardiovascular and all-cause mortality in diastolic heart failure.

Background
Recent studies have demonstrated that VE/VCO
2
was more powerfully predicted mortality, hospitalization, or both than VO
2
in systolic heart failure.

Methods and Results
The outpatients previously diagnosed as diastolic heart failure were recruited from April 2006 to March 2007, and underwent cardiopulmonary exercise testing and echocardiographic examination. Plasma BNP concentration was measured. Total of 224 patients were enrolled. During a mean follow-up of 30 months, 57 patients died (36 from cardiovascular death). Univariate Cox regression analysis showed that age, New York Heart Association function class, atrial fibrillation, diabetes mellitus, left ventricular diastolic dysfunction, peak VO
2
, VE/VCO
2
, and plasma BNP were significantly associated with mortality risk. Multivariate analysis revealed that plasma BNP, VE/VCO
2
, and age remained independent predictors for both cardiovascular and all-cause mortality, with the strongest prognostic values of plasma BNP (chi square =35.9 vs 39.8; P<0.001). In addition to clinical risk factors and plasma BNP, The VE/VCO
2
could provided incremental and independently prognostic information of cardiovascular (chi square =60.6 vs 51.7; P=0.009) and all-cause mortality (chi square =62.8 vs 54.2; P=0.015) with increased chi square value of Cox regression model.

Conclusion
In patients with diastolic heart failure, plasma BNP is the strongest predictor of mortality risk, and VE/VCO
2
, but not peak VO
2
, provides addictive independent prognostic information, which suggests that combination of plasma BNP and VE/VCO
2
can improve risk stratification.
Abstract 17770: Utility of Plasma B-Type Natriuretic Peptide Levels for Cardiovascular Risk Assessment in Subjects with Albuminuria
Authors: Segawa Toshie , Tanaka Fumitaka , Makita Shinji , Onoda Toshiyuki , Ohsawa Masaki , Tanno Kozo , Itai Kazuyoshi , Sakata Kiyomi , Nakamura Motoyuki
Published: April 2024

Background:
The subjects with albuminuria is a high risk group for cardiovascular disease (CVD). Also, increased plasma B-type natriuretic peptide (BNP) levels have been reported to be associated with CVD risk in several clinical and population-based settings. However, it remains unknown whether CVD risk in subjects with albuminuria could be stratified by plasma BNP levels.

METHODS:
At baseline, we measured spot urinary albumin/creatinine concentrations (UACR) and plasma BNP concentration in the general population (n = 15,344). Albuminuria was defined by UACR more than 30 mg/g creatinine (Cr). Data from 3,214 subjects aged 40 to 80 (mean age = 65 years) with no cardiovascular history were analyzed. The cohort was divided into quartiles according to plasma BNP, and the CVD event free rate within each BNP quartile was estimated using the Kaplan-Meier method. In addition, Cox regression analysis was performed to examine the relative risk of onset of CVD events among the quartiles.

RESULTS:
The mean follow-up duration was 5.7 years. Cases admitted for CVD events (heart failure, stroke, myocardial infarction) in the cohort were surveyed prospectively. The event free rate of the highest BNP quartile showed the lowest event free ratio (p < 0.001). After adjustment for established CVD risk factors including glycosylated hemoglobin (HbA1c) values and estimated glomerular filtration rate (eGFR), the hazard ratio (HR) for CVD events increased significantly according to BNP quartile (p for trend < 0.001), and the HR for the highest BNP quartile was significantly elevated compared to that for the lowest quartile (HR = 2.43, 95% CI; 1.44 - 4.09: Figure). When subjects with diabetes or reduced eGFR (<60) were excluded, the association remained to be robust (Figure).

CONCLUSION:
Elevated plasma BNP levels are a useful biomarker for CVD risk stratification in subjects with albuminuria independent of classical risk factors including diabetes or renal dysfunction.
Abstract 17942: A Novel Transgenic Pig Model Overexpressing Ectonucleoside Triphosphate Diphosphohydrolase 1 (entpd-1/cd39) Demonstrates Reduced Myocardial Injury
Authors: Mahamud Shouvik , Wheeler Debra G , Jospeh Matthew , Dwyer Karen M , Nottle Mark B , Harrison Sharon J , Robson Simon C , Cowan Peter J , d'Apice Anthony J , Gumina Richard J
Published: April 2024

Background:
Ectonucleoside Triphosphate Diphosphohydrolase-1 (ENTPD-1/CD39) rapidly converts ATP and ADP to AMP which is further degraded by ecto-5’-nucleotidase (CD73) to adenosine, an anti-thrombotic, vasodilatory and cardiovascular protective mediator. The objective was to determine whether overexpression of ENTPD1 reduces myocardial ischemia-reperfusion injury in a large animal model of myocardial injury.

Methods:
Transgenic pigs expressing human ENTPD-1 under the control of the H-2Kb promoter were generated via somatic cell nuclear transfer. Myocardial ischemia-reperfusion (I/R) injury was evaluated in transgenic pigs overexpressing human ENTPD1 (CD39). I/R injury was induced by intracoronary balloon inflation in the left anterior descending (LAD) artery for 60 min followed by 3 hours of reperfusion. Myocardial infarct size was determined by staining with triphenyl tetrazolium chloride (TTC) and the area-at-risk was delineated by perfusion with 5% Phthalo Blue. For all assessments the operator was blinded to animal genotype.

Results:
Expression of ENTPD1 in the cardiac tissue was confirmed by Western analysis and immunohistochemistry. In response to 60 minutes of left anterior artery ischemia followed by 3 hours of reperfusion, ENTPD1 animals displayed a marked reduction in infarct size compared to wild-type littermate controls (WT: 44.7±5.2% vs ENTPD1: 17.2±4.3%; Figure).

Conclusions:
Overexpression of human ENTPD1 significantly attenuates myocardial infarction in a novel large animal transgenic model of myocardial ischemia-reperfusion injury.
Abstract 17974: Prognostic Impact After Acute Kidney Injury in Patients with Acute Heart Failure: An evaluation of the RIFLE Criteria
Authors: Shirakabe Akihiro , Hata Noritake , Shinada Takuro , Kobayashi Nobuaki , Tomita Kazunori , Kitamura Mitsunobu , Matsushita Masato , Asai Kuniya , Mizuno Kyoichi
Published: April 2024

Background:
The clinical course and the outcome of acute heart failure (AHF) are known to correlate with renal dysfunction. However, the evaluation of renal dysfunction, especially acute kidney injury (AKI), has not yet been standardized. This study, therefore, investigated the relationship between the short term and long term prognosis of AHF and AKI using the risk, injury, failure, and end stage (RIFLE) criteria.

Methods and Results:
This study analyzed seven hundred ten patients with AHF who were admitted to the intensive care unit. The most severe RIFLE classifications during hospitalization were adopted to assess the patient outcome. The AHF patients were assigned to no AKI (n=244), Class R (risk; n=259), Class I (injury; n=106), and Class F (failure; n=101). This study evaluated the relationships between the RIFLE classifications and in-hospital mortality, cardiovascular death and HF events including cardiovascular death, and readmission to the hospital for HF within 2 years. The results of the multivariate logistic regression model for in-hospital mortality found that the specific factors were Class I (p=0.005, hazard ratio: 4.01; 95% CI: 1.51-10.69) and Class F (p<0.001, hazard ratio: 10.64; 95% CI: 4.21-26.90). Furthermore, Class I and Class F were independently associated with cardiovascular death (Class I p=0.006, hazard ratio: 2.49; 95% CI: 1.31-4.75, Class F p<0.001, hazard ratio: 5.42; 95% CI: 2.84-10.35) and Class F were independently associated with HF events (p<0.001, hazard ratio: 3.09; 95% CI: 1.76-5.43). The Kaplan-Meier survival curves showed the prognosis including cardiovascular death to be significantly poorer among the patients with Class I and Class F in comparison to no-AKI and Class R (p<0.001, Log-Rank test), and the prognosis including HF events to be significantly poorer among the patients with Class F in comparison to no-AKI, Class R and Class I (p<0.001, Log-Rank test).

Conclusions:
The presence of severe AKI (Class I and F) was found to be independently associated with both short-term and long-term mortality in patients with AHF, however, mild AKI (Class R) and no AKI were not associated with those events. The RIFLE criteria should therefore be developed into a clinically applicable and standardized method for AHF patients.
Abstract 18016: Real Time MRI To Detect and Target Gaps in Radiofrequency Ablation Lesions
Authors: Ranjan Ravi , Kholmovski Eugene G , Vijayakumar Sathya , Blauer Joshua , MacLeod Rob , Marrouche Nassir F
Published: April 2024

Introduction:
Radiofrequency ablation is routinely used to treat numerous cardiac arrhythmias including atrial fibrillation. Due to the lack of any direct visualization of changes at the tissue level with ablation gaps remain in ablation lesion sets. In this study we investigated using MRI to identify these gaps in lesions sets and target them acutely.

Methods:
The study was carried out in pigs (n=5). Two discrete lesions were created in the right atrium spaced 10 mm apart using the CARTO (Biosense Webster, Diamond Bar, CA) electro-anatomical mapping system under fluoroscopy. The animal was then moved to the MRI scanner (3T, Verio, Siemens Healthcare, Germany) where delayed enhancement image after gadolinium infusion was acquired and used to identify the lesions and the gap in between them. Using real time catheter visualization in MRI the gap area was ablated using MRI compatible catheters (MRI Interventions Inc, Irvine, CA).

Results:
Panel A shows the two right atrial lesions and the gap in between as seen in MRI using delayed enhancement (lesions marked by white and green arrows). Panel B is a snap shot from the real time MRI showing the segmented right atrial shell with the lesions and the MRI catheter targeting the gap between the lesions. Panel C shows the delayed enhancement image acquired after ablation in the MRI scanner confirming that the gap area is ablated (yellow arrow). Panel D is a cross section of the right atrial tissue specimen showing the two lesions made using CARTO (white and green arrows) and the ablated gap area (yellow arrow) in between. We were able to detect gaps upto 2.6 mm in using delayed enhancement in MRI.

Conclusions:
Real time MRI can be used to identify gaps in lesion sets and target them acutely potentially leading to significant improvement in outcomes of ablation procedures.
Abstract 18045: Can Metabolic Syndrome Predict the Vulnerable Plaque in Patients with Stable Angina Pectoris?: Virtual Histology-Intravascular Ultrasound Analysis
Authors: Lee Min Goo , Jeong Myung Ho , Park Keun Ho , Sim Doo Sun , Hong Young Joon , Kim Ju Han , Ahn Youngkeun , Kang Jung Chaee
Published: April 2024

Background-
Vulnerable plaque (VP) in coronary artery can progress to plaque rupture and thrombosis, and have a strong potential to induce acute coronary syndrome. Many studies have demonstrated that metabolic syndrome (MS) is associated with increased risk for cardiovascular diseases and related mortalities. This study aimed to determine the predictive value of MS on VP in the patients with stable angina pectoris (SAP).

Methods and Results-
From September 2007 to June 2010, a total of 239 patients with SAP who underwent coronary angiogram and intravascular ultrasound were categorized into two groups: MS group (n = 100, 56 men, 64.7 ± 9.5 years) and non-MS group (n = 139, 98 men, 60.2 ± 8.4 years). National Cholesterol Education Program-Adult Treatment Panel III guideline was used to determine the presence of MS and diverse variables containing IVUS findings were compared between two groups. MS group were older age and more likely to be women than non-MS group (p <0.001, p = 0.021, respectively). MS group showed more frequent multivessel involvement (p = 0.026) and had more distal target vessel in coronary artery (p = 0.005) than non-MS group, but IVUS finding containing the plaque burden showed no significant difference between two groups. In addition, low high density lipoprotein (HDL) cholesterol level as the criteria of MS (male <40 mg/dl, female <50 mg/dl) was observed in VP group more than stable plaque group (p = 0.020), but the prevalence of MS and other components of MS were not different between two groups. Multivariate analysis using logistic regression for the presence of VP showed that the independent predictor is the low HDL cholesterol level (odds ratio = 3.563, 95% confidence interval = 1.370-9.269, p = 0.009).

Conclusions-
Low HDL cholesterol level, but not MS, is the independent predictor of VP as a culprit lesion in SAP patients.
Abstract 18132: Multicenter Non-Randomized Prospective Cohort Study of Extracorporeal Cardiopulmonary Resuscitation for Out-of Hospital Cardiac Arrest: Study of Advanced Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan (SAVE-J)
Authors: Sakamoto Tetsuya , Asai Yasufumi , Nagao Ken , Yokota Hiroyuki , Morimura Naoto , Tahara Yoshio , Atsumi Takahiro , Hase Mamoru , Nara Satoshi ,   SAVE-J study group
Published: April 2024

Background:
This study is aimed to examine the efficacy of extracorporeal cardiopulmonary resuscitation (ECPR) for patients in out-of hospital cardiac arrest (OHCA) with ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT).

Method:
The design of this study is a multicenter non-randomized prospective cohort study. Hypothesis is that the outcome of OHCA with VF or pulseless VT is similar between ECPR and conventional advanced life support (ALS). During from Oct. 2008 to Dec. 2010, forty six tertiary emergency hospitals were participated in this study. Patient inclusion criteria were 1) VF or pulseless VT on scene, 2) cardiac arrest on arrival at hospital, 3) within 45 minutes from a call to an arrival of hospital, and 4) non-ROSC by conventional ALS during 15 minutes after an arrival at hospital. Exclusion criteria were 1) age: 75 yr, 2) poor activities of daily livings, 3) non-cardiac verified cardiac arrest, and 4) hypothermia. According to the inclusion criteria, ECPR was adopted for OHCA in 26 hospitals (ECPR group) and conventional ALS was planned in 20 hospitals (non-ECPR group). Both groups (Intention-to-treat) were analyzed about the proportion of patients with favorable outcome (CPC1 or 2) assessed with the Glasgow-Pittsburgh Cerebral Performance and Overall Performance Categories at 1 month by chi square test and Fisher exact probability test.

Results:
One hundred and eighty patients of ECPR group and 134 patients of non-ECPR group were enrolled. There was no difference between the background of ECPR group and non-ECPR group; Average age (56.0 VS 56.9), Witnessed (72.8% VS 75.4%), Lay-rescuer CPR (49.4% VS 45.5%), Acute coronary syndrome (65.6% VS 61.4%), Minutes from collapse to emergency department (26.8 VS 30.0). The favorable outcome rate in ECPR group (12.4%, 22 patients) was statistically higher than the rate in non-ECPR group (1.6%, two patients) (p<0.001).

Conclusion:
Extracorporeal cardiopulmonary resuscitation may improve the outcome of out-of hospital cardiac arrest with VF or pulseless VT without ROSC by conventional ALS during 15 minutes after an arrival at hospital.
Abstract 18138: Molecular Mechanism Whereby Activated State of the Angiotensin II Type 1 Receptor Attenuate Inverse Agonist Efficacy
Authors: Takezako Takanobu , Ishiguro Masaji , Karnik Sadashiva S , Baba Hisamitsu , Node Koichi
Published: April 2024

Angiotensin II type 1receptor (AT1R) can be activated by mechanical stress without involving angiotensin II stimulation, and play a critical role in the cause of cardiac hypertrophy. AT1R blocker (ARB) can prevent it by inverse agonist action. The binding affinity of the ARBs has been known to be strongly reduced in activated state of the AT1R compare to in the ground state of the AT1R. It suggests that active conformational change of the AT1R alter binding mode of ARBs, and thereby alter the inverse agonist efficacy. We compared inverse agonist efficacy of four ARBs (Losartan, EXP3174, Irbesartan and Valsartan) between ground state and activated state of the AT1R, and found that active conformational change of the AT1R strongly attenuate the inverse agonist efficacy of all four ARBs. Hence, we examined the molecular mechanism whereby activated state of the AT1R attenuates the inverse agonist efficacy of the ARBs by performing site-directed mutagenesis, ligand binding, inositol phosphate formation, and molecular modeling. AT1 wild type (AT1WT) and constitutively active N111G mutant used as model of ground state and activated state of the AT1R, respectively. Since identifying the molecular mechanism of the inverse agonism will be useful for developing new strong inverse agonistic ARB. Molecular models based on the effect of mutant on binding affinity and inverse agonist efficacy of the ARBs suggest that interactions of ARBs with Val108 and Ser109 in transmembrane domain (TM)3, Gln257 in TM6, and Asn295 in TM7 stabilize the AT1R in inactive conformation, and causes inverse agonist activity. Molecular models also suggest that active conformational change of the AT1R attenuate the interaction of ARBs with Gln257 and Asn295, and thereby attenuate stabilizing the AT1R in inactive conformation, resulting in attenuated inverse agonist efficacy. We conclude that attenuation of the interaction with TM6 and TM7 is molecular mechanism whereby activated state of the AT1R attenuates the inverse agonist efficacy of ARBs. Our findings will be useful for developing new class of strong inverse agonistic ARB.
Abstract 18214: Interpreting Troponin Elevation in Relation to Symptom Onset in Intermediate-Risk Pulmonary Embolism
Authors: Meneveau Nicolas F , Janin Sebastien , Chopard Romain , Seronde Marie-France , Schiele Francois , Bernard Yvette
Published: April 2024

Background:
Troponin dosage plays an increasingly important role in risk stratification in pulmonary embolism (PE), especially in patients (pts) without hemodynamic compromise. Troponin elevation in the setting of acute PE is of small magnitude and short duration and thus, can go unnoticed in pts referred late after symptom onset.

Methods:
Prospective, single-center registry of patients with confirmed intermediate-risk PE, defined as at least 1 echocardiographic finding indicating right ventricular (RV) dysfunction (RV/left ventricular end-diastolic diameter ratio * 1 in the 4-chamber view, paradoxical septal systolic motion or pulmonary hypertension defined as a RV/atrial gradient >30 mmHg), or a positive troponin test. We used a combined in-hospital endpoint defined as death, non-fatal recurrent PE, or residual pulmonary vascular obstruction (RPVO) >30% as measured by V/Q scan before discharge.

Results:
In total, 199 patients were included, average age 69±15, 56% women, 116 (58%) pts referred within ≤5 days after symptom onset, and 83 (42%) after >5 days, of whom 25 were referred after >15 days since symptom onset. All patients had at least 1 sign of RV dysfunction. Troponin elevation was observed in 78/116 pts (67.2%) treated within ≤5 days, and in 40/83 pts (48.2%) treated after >5 days (p=0.03). Sensitivity and specificity of troponin elevation to predict adverse outcome as defined above are shown in the table.

Conclusion:
Our results show that there is a significant relation between troponin elevation and symptom onset in patients with intermediate-risk PE. Time since symptom onset should be taken into consideration when interpreting troponin elevation in this population. Negative predictive value of troponin elevation is adequate in pts treated early (≤5 days) but is suboptimal in pts treated >5 days after symptom onset.
Abstract 18242: High Dose Statin Results in a Further Reduction in Atherosclerotic Inflammation Compared with Low Dose Statin: Results of a Multi-Center PET-CT Study
Authors: Tawakol Ahmed , Fayad Zahi A , Mogg Robin , Alon Achilles , Subramanian Sharath , Abdelbaky Amr , Nunes Irene , Herman Gary , Beals Chan , Shankar Sudha S
Published: April 2024

Background:
Statin treatment results in a reduction in cardiovascular mortality. Here we test the hypothesis in a double-blinded multi-center randomized trial using fluorodeoxyglucose positron emission tomography imaging (FDG-PET), that high dose statins results in further reduction in plaque inflammation compared to low dose statins.

Methods:
Adults with risk factors for or established atherosclerosis, who were not already on high-dose statin (n= 83, median age 59 yrs, range 37-78 yrs, 78% men), were randomized (1:1) to 10 vs. 80mg of atorvastatin. FDG-PET imaging was performed before and 12 wks after randomization to measure atherosclerotic inflammation in the aorta and carotids. Arterial wall FDG uptake (target) was normalized to blood pool (background), yielding a target to background ratio (TBR). The most diseased segment (MDS) was defined as the 1.5 cm segment that included the highest TBR at baseline. All analyses were performed while blinded to time points and treatment.

Results:
Sixty-seven individuals completed the protocol and provided data for analysis. At 12 wks, inflammation (TBR) in the MDS was significantly reduced in atorva 10mg (% reduction from baseline [90% CI], 6.3 [1.2,11.2], 2-sided p< 0.05, fig A), as well as atorva 80mg groups (14.6 [9.7, 19.2], p<0.001). Moreover, atorva 80 resulted in a significant additional reduction in TBR relative to atorva 10 (%relative additional reduction= 8.8 [1.6, 15.6], p<0.05). Further, a reduction in TBR was seen in patients randomized to atorva 80 who were already on a low-dose statin at baseline, (13.5 [6.9, 19.6], p=0.002, fig B). Changes in TBR did not correlate with changes in lipids.

Conclusions:
We observe a dose-related reduction in atherosclerotic inflammation in this first multi-center double-blinded trial evaluating effect of statins on FDG-PET measures of atherosclerotic inflammation. FDG-PET imaging may provide a useful assessment of treatment effect in patients already taking statins.
Abstract 18263: Incident Heart Failure and All-Cause Mortality in Older Current Smokers and Former Smokers with 15 or More Years of Abstinence: Findings From a Prospective Population Study
Authors: Ahmed Amiya A , Fonarow Gregg , Filippatos Gerasimos , Zhang Yan , Aban Inmaculada , Anastasiou-Nana Maria , Aronow Wilbert , Sawyer Patricia , Allman Richard , Ahmed Ali
Published: April 2024

Background:
The 2004 Surgeon General's Report on “The Health Consequences of Smoking” suggests that after 15 years of abstinence, the cardiovascular (CV) risk of smoking becomes similar to that of never-smokers. At the AHA2010, we presented data that indicated that while that is true for most older former smokers, this benefit may not extend to older former heavy (≥32 pack-years) smokers. While the CV risk of former heavy smokers may take much longer than 15 years to become like that of never smokers, it is believed that the risk may be reduced compared to current smokers. In the current analysis, we compared the CV risk of older adults who quit smoking >15 years ago relative to older current smokers.

Methods:
Of the 5795 community-dwelling older adults, age ≥65 years, in the public-use copy of the Cardiovascular Health Study data obtained from the NHLBI, 5604 had detailed data on current and past smoking. Of these, 5338 were free of prevalent HF at baseline. Of these, 629 were current smokers and 1298 were former smokers who quit >15 years ago, who were categorized as former heavy (≥32 pack-years; n=312) and former light (<32 pack-years; n=986) smokers.

Results:
Patients had a mean (±SD) age of 73 (±5) years; 45% were women; and 14% were African American. Former heavy smokers were older and more likely to be white men (
Table
). Unadjusted, age-sex-race-adjusted and multivariable-adjusted risk of centrally-adjudicated incident HF and all-cause mortality associated with former light and heavy smoking relative to current smokers during over 13 years of follow-up are displayed in the
Table.

Conclusions:
Among community-dwelling older adults, compared with current smokers, former smokers who quit smoking >15 years ago had substantial and significant independent reduction in all-cause mortality regardless of amount and duration of smoking prior to cessation. However, the association with reduced risk of incident HF was only significant for older former light (<32 PY) smokers.
Abstract 18311: Mechanism of Cardiovascular Benefit From Exercise in Women: Not Through Subclinical Atherosclerosis!
Authors: DeFina Laura , Radford Nina , Leonard David , Berry Jarett , Khera Amit
Published: April 2024

Introduction:
Cardiorespiratory fitness (CRF) has been shown to be inversely associated with coronary heart disease (CHD) morbidity and mortality. The cardioprotective mechanism of fitness has not been well defined. The goal of this study was to assess the relationships among subclinical coronary artery calcification as a measure of atherosclerotic burden, self reported PA and measured CRF in a single large population of generally healthy women.

Methods:
6,148 women seen in a single medicine clinic between 1998 and 2007 provided self-reported measures of PA, underwent maximal treadmill exercise testing, and CAC scanning. PA was reported in MET·min per week. CRF was reported in METs derived from the maximal treadmill time. CAC was evaluated as a dichotomous variable. We used multiple logistic regression to calculate adjusted odds ratios (OR) for CAC > 0, and we applied a nonparametric trend test to the relationship between PA and CRF.

Results:
The mean age was 50.9 years (±8.9). The overall prevalence of CAC was 18.8%. CAC was directly related to age, hypertension, diabetes, hyperlipidemia, and family history of CHD. Figure 1 shows mean CAC by quartile of CRF without adjustment for other covariates. When adjusted for age, the association between CAC and CRF remained significant (OR=0.995 [0.992,0.998] per MET, p<0.001) but not when adjusted for age, hypertension, diabetes, hyperlipidemia, smoking, and family history (OR=0.998 [0.995,1.001] per MET, p=0.14). CAC was not associated with PA when adjusted for age or all covariates. In this large population, we also found a direct relationship between self-reported PA and CRF (p<0.001).

Conclusions:
The cardiovascular benefit of self reported PA or quantitative CRF, does not appear to be mediated by the modification of absolute calcific atherosclerotic burden in women.
Abstract 18433: A Novel Intracellular Isoform of Matrix Metalloproteinase-2 Activates Innate Immunity and Leads to Cardiac Failure
Authors: Lovett David H , Mahimkar Rajeev , Maklashina Elena , Cecchini Gary , Karliner Joel S
Published: April 2024

Modulation of cardiac structure and function by matrix metalloproteinases (MMP) is an area of intense interest. Experimental and clinical evidence has pinpointed a critical role for a specific enzyme, MMP-2, in ventricular remodeling and systolic failure. Transgenic expression of active 68 kDa MMP-2 yields multiple defects, including systolic failure and mitochondrial dysfunction. We hypothesized that an additional intracellular isoform of MMP-2 must exist that initiates mitochondrial dysfunction and inflammation. Western blots of mitochondria from ageing mice and a transgenic model of atherogenesis revealed a smaller 65 kDa MMP-2 isoform. Cardiomyoblast cells subjected to transient inhibition of oxidative phosphorylation also generated the mitochondrial 65 kDa MMP-2 isoform. MMP-2 contains three in-frame methionines in the N-terminus, each with a Kozak sequence supporting translational initiation. The 65 kDa MMP-2 isoform is an N-terminal truncation variant generated by alternative translational start site selection at M
77
, thereby deleting the signal sequence and the inhibitory prodomain: thus the 65 kDa MMP-2 is intracellular and enzymatically active. A portion of the 65 kDa MMP-2 localizes in the mitochondrial intramembranous space, triggers mitochondria-to-nuclear stress signaling and actvitates NF-κB and NFAT. Microarray analysis showed that 65 kDa MMP-2 induces a restricted innate immune response transcriptome, including viral stress response genes (OAS1, IFIT, PRKRA), the crucial innate immunity transcription factor IRF7, chemokines and pro-apoptosis genes. Cardiac-specific transgenic expression of the truncated MMP-2 isoform induced progressive cardiomyocyte and ventricular hypertrophy, followed by mononuclear inflammatory cell infiltration and cardiomyocyte apoptosis, as predicted from the microarray results. Functionally, the transgenics showed cardiomyocyte hypertrophy, contractile defects, systolic failure and enhanced injury following ex vivo ischemia/reperfusion.

Conclusion:
a novel intracellular isoform of MMP-2 is generated by acute or chronic oxidative stress, initiates inflammatory signaling and drives cardiomyocyte apoptosis, features directly relevant to clinical cardiac disease.