bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 3095: Prognostic Significance Of Post-revascularisation Irreversible Myocardial Injury Detected By Cardiovascular Magnetic Resonance Imaging
Authors: Selvanayagam Joseph B , Rahimi Kazem , Banning Adrian , Cheng Adrian S , Pegg Tammy J , Karamitsos Theodoros D , Taggart David P , Neubauer Stefan , Neubauer Stefan
Published: July 2021

Background
The prognostic significance of revascularization procedure related myocardial injury is uncertain. Delayed enhancement CMR (DE-CMR) has been shown to reliably identify areas of irreversible myocardial injury. We evaluated the prognostic significance of procedure related myocardial injury in a consecutive series of patients undergoing high risk PCI or CABG.

Methods/Results
152 patients underwent DE-CMR pre and 1– 6 days post elective PCI or CABG. Primary endpoint was defined as total mortality, non-fatal MI, ventricular arrhythmia terminated by ICD (VA), and unstable angina or heart failure requiring hospitalization. Secondary endpoint was the composite of total mortality, non-fatal MI and VA. During a median follow-up of 2.9 years, 27 patients (18%) reached the primary endpoint and 12 patients (8%) the secondary endpoint. 49 patients (32%) had evidence of new myocardial hyperenhancement (HE) with a median mass of 5.0g (IQR 4.8 –7.1). In a univariate analysis, age, LV EF post intervention, and presence of new HE were predictive of the primary outcome. Elevated troponin (at 24 h) showed a trend towards poorer outcome. In a multivariate Cox regression analysis only age and presence of new HE (HR 2.7, 95% CI 1.1, 5.8) remained independently correlated with occurrence of the primary endpoint. New myocardial HE was the single independent predictor of the composite secondary endpoint (HR 4.2 95% CI 1.2, 16.1).

Conclusion
Even small amounts of procedure-related myocardial injury are associated with poorer medium term clinical outcomes. CMR identified myocardial injury may be a stronger prognostic marker than cardiac troponin in the setting of coronary revascularisation.
Abstract 3096: Does The Extent Of Non Viable Myocardium, As Identified By Delayed Enhancement Cardiac Magnetic Resonance, Preclude Response After Cardiac Resynchronization Therapy?
Authors: Parsai C , Bunce N , Sutherland G.R , Baltabaeva A , Bijnens B , O’Donnell M , Barros J , Anderson L
Published: July 2021

Cardiac resynchronisation therapy (CRT) is a recognised treatment for symptomatic left ventricular (LV) failure associated with a broad QRS.It has been suggested that >15% myocardial scarring predicted failure to respond to CRT. To determine if the scar burden is a major determinant in response to CRT, we prospectively studied 50 pts (66± 1 years, ischaemic aetiology 57%) undergoing CRT for standard indications at baseline (NYHA: 3±0.4, EF: 23±0.8%, QRS: 150±7 ms, BNP: 495±461 pmol/l) and 6 months post-CRT. Clinical response was defined by a reduction in NYHA class >1 and in BNP level >30%. Reverse LV remodelling was defined as a reduction in end-systolic volume ≥10%. All patients had an echocardiographic examination, including an assessment of dyssynchrony. Additionally, a Cardiac Magnetic Resonance (CMR) study, with delayed enhancement, was performed in patients without contraindications. Of the 30 patients that had CMR, 23 pts (77%) responded clinically to CRT (reduction in NYHA: 1.6±0.6, reduction in BNP: 34±0.4%) and 19/30 (63%) additionally displayed reverse LV remodelling. Among the clinical responders 8 pts (35% of responders) were found to have extensive full thickness myocardial scarring on CMR (in 7 ±1 segments), predominantly in the anteroseptum and apex (86%). Three of these patients also showed significant echocardiographic reverse remodelling. The mechanism of response to CRT in these patients with extensive infarction was more frequently interventricular resynchronisation (43%) or atrio-ventricular resynchronisation (43%) rather than intra-ventricular resynchronisation (14%).The previously suggested 12 segment dyssynchrony index (DI) would have identified none of these responders with extensive myocardial infarction. The DI identified only 7/23 responders (30%).

Conclusion
: Even patients with extensive myocardial scar are potential responders to CRT and should not be excluded if they fulfil the standard AHA/ESC criteria for biventricular pacing. Intraventricular resynchronisation is not the only mechanism by which patients respond to CRT and measures of intraventricular dyssynchrony alone are inadequate for identifying potential response
Abstract 3106: Are we Considering the Best Hemodynamic Predictor of Cardiovascular Death?
Authors: Rafie Amir H Sadrzadeh , Sungar Gannon W , Hadley David , Myers Jonathan , Froelicher Victor F
Published: July 2021

Introduction:

While prognostic importance of exercise capacity (in [METs]) is well established, there is controversy regarding the relative prognostic potential of other hemodynamic responses. The high correlation of these variables conflicts with the assumptions of survival analysis models.

Objective:

To assess the prognostic power of double product (DP) because it combines heart rate (HR) and systolic blood pressure (SBP).

Methods:

From a total of 1959 consecutive patients referred for exercise testing at the Palo Alto Veterans Affairs Medical Center from 1997 to 2004, we studied 1759 male veterans (mean ± SD age, 57 ± 12 years) free of heart failure. DP was calculated by multiplying SBP and HR; variables and their products were subtracted to obtain the differences between rest and maximal exercise (reserve) and recovery (HRR). The hemodynamic variables were analyzed using multiple linear regressions and Cox hazard models with cardiovascular death as the outcome.

Results:

There were 157 all-cause deaths, with 53 of the deaths being due to cardiovascular causes (34%) during a median follow up of 5.2 years. Though most of the hemodynamic variables were individually significant in Cox analysis, when age, DP reserve, METs and HRR were entered together, only age and DP reserve were chosen. Of all hemodynamic measurements considered, DP reserve was the strongest predictor of cardiovascular prognosis after adjustment for β-blocker use (Wald Z-score, −5.12; P<0.001).

Conclusions:

In patients referred for exercise testing, DP reserve had greater prognostic power than METs, maximal HR or SBP, or HR recovery.

Figure 1.

Kaplan-Meier survival curves for normal subjects according to DP reserve.
Abstract 3113: Uncontrolled Hypertension, Systolic and Diastolic Blood Pressure and Development of Symptomatic Peripheral Arterial Disease in the Women’s Health Study
Authors: Powell Tiffany M , Glynn Robert J , Creager Mark A , Ridker Paul M , Pradhan Aruna D
Published: July 2021

Background
: Prospective data pertaining to risk factors for peripheral arterial disease (PAD) in women are sparse. Few studies have evaluated blood pressure, including uncontrolled hypertension, and PAD onset in women.

Methods and Results
: We examined the relationship between blood pressure and development of confirmed symptomatic PAD (n=116 events) in a prospective cohort study of 39,261 female health professionals aged ≤ 45 years without diagnosed vascular disease at baseline. Median follow-up was 11.4 years. Women were first grouped according to baseline presence of uncontrolled hypertension, defined as reported systolic blood pressure (SBP)≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg, and pharmacologic treatment status. SBP and DBP were then modeled as continuous and categorical exposures irrespective of treatment status. Pulse pressure (PP) and mean arterial pressure (MAP) were also assessed. Age-adjusted and multivariable-adjusted risk estimates were derived from Cox proportional hazards models. Women with treated but uncontrolled hypertension had the highest risk of symptomatic PAD (0.67 events per 1000 person-years). Adjusted hazard ratios (HRs) compared to women without hypertension were 1.1 (95% CI, 0.5–2.3) for women who were treated and controlled, 1.7 (95% CI, 1.0 –3.0) for women untreated and uncontrolled, and 2.3 (95% CI, 1.4 – 4.0) for women treated and uncontrolled (p-trend<0.001). When hypertension was examined using continuous and categorical measures, there was a 33% increase in risk per 10 mmHg of SBP (95% CI, 18 to 47%) and a positive gradient in multivariable-adjusted risk according to SBP category (<120, 120 –139, 140 –159, and ≤ 160 mmHg); HRs were 1.0, 1.6, 2.8, and 4.3 (p-trend<0.001), respectively. We also considered DBP, PP, and MAP. While individually predictive, none was a stronger predictor than SBP with none adding predictive ability beyond SBP.

Conclusions
: Uncontrolled hypertension is associated with incident symptomatic PAD in women. Among blood pressure variables assessed, SBP is the best single predictor. These data support a strong prognostic role for systolic blood pressure in the development of peripheral atherosclerosis in women.
Abstract 3115: Ankle Brachial Pressure Index (ABI) Is A Better Predictor Of Cardiovascular Mortality Than Toe-Brachial Index (TBI) Or Abnormal Doppler Flow Curves In Both Diabetic And Non-diabetic Subjects: The Hoorn Study.
Authors: Huijberts Maya S , Ferreira Isabel , Schaper Nicolaas C , Dekker Jacqueline M , Nijpels Giel , Heine Robert J , Stehouwer Coen D
Published: July 2021

Introduction:
Individuals with peripheral arterial disease (PAD) have a high risk of future cardiovascular events. Many studies have demonstrated that low (<0.9) Ankle Brachial Index (ABI) predicts cardiovascular mortality in both diabetic and non-diabetic subjects. However, in diabetic subjects the measurement of the ABI is complicated by the presence of medial arterial calcification which results in falsely elevated ABI-values despite the presence of significant PAD. Therefore, we investigated whether the Toe-Brachial Index (TBI) or abnormal Doppler flow curves would be better predictors of PAD-associated cardiovascular mortality (CVM).

Methods:
Associations between measures of PAD and CVM were studied in an age-, sex,- and glucose tolerance stratified sample (n = 631) of a population based cohort aged 50 –75 years followed for 15 years. Measures included Doppler assisted ABI, flow velocity tracings of the femoral, popliteal and crural arteries and measurement of the TBI. Predictors of CVM were determined by Cox proportional hazards multiple regression analysis. Results are described as hazards ratios (HR) and 95% confidence intervals (CI).

Results
: At baseline ABI < 0.9 was present in 10.5% (6.9% in non-diabetic vs 17.2% in diabetic individuals), TBI < 0.7 was present in 21.0% (18.9% vs 24.3%), and abnormal Doppler flow curves in 20.3% (16.0% vs 29.3%). After 15 years of follow-up 141 patients had died of cardiovascular causes. After adjusting for age, sex, hypertension, total and HDL-cholesterol, triglycerides, BMI and smoking, HR (95% CI) were 3.19 (1.91–5.34) P<0.001 for ABI<0.9, 2.80 (0.97– 8.05) P=0.056 for presence of abnormal flow-curves, and 1.58 (0.97 – 2.57) P=0.068 for TBI<0.7. When entering the three measures simultaneously in the regression model only ABI<0.9 was an independent predictor of CVM, HR=2.81 (1.47 – 5.39) P=0.002. In diabetic individuals this effect was as least as strong, HR=3.30 (1.39 – 7.99) P=0.007.

Conclusion:
Although an ABI< 0.9 may underestimate the presence of PAD in individuals with type 2 diabetes, this measure is a powerful independent predictor of CVM in both diabetic and non-diabetic subjects. Assessment of the ABI should be used more often to identify high-risk patients, especially in the diabetic population.
Abstract 148: Superoxide Promotes Reversible Uncoupling Of Inducible Nitric Oxide Synthase, While Peroxynitrite Induces Irreversible And Complete Enzyme Inactivation
Authors: Sun Jian , Druhan Lawrence J , Zweier Jay L
Published: July 2021

Inducible nitric oxide synthase (iNOS) is present in the post-ischemic heart, and plays an important role in the pathogenesis of injury and remodeling. Oxidants formed during reperfusion injury are known to alter NOS function. In this study we compare and contrast how two biologically relevant oxidants, peroxynitrite (ONOO
−
) and superoxide (O
2
−
), alter iNOS function and define the mechanisms involved for each. Nitric oxide (NO) generation rate of purified iNOS was quantified by the methemoglobin formation, O
2
−.
generation was measured using EPR spin-trapping, and the quaternary structure of iNOS by size-exclusion FPLC. Tetrahydrobiopterin (BH
4
)-replete iNOS (1 μM) was exposed to O
2
−.
, and ONOO
−
in concentrations from 0.01 μM to 500μM and NO production was measured with and without addition of excess BH
4
. ONOO
−
(50μM) decreased NO production to 19% ± 0.17 and excess BH
4
only partially restored activity to 48% ± 3.4. O
2
−.
(50 μM) reduced NO production to 42% ± 1.2 and the excess BH
4
completely restored activity to 100% ± 3.1. ONOO
−
exerted the highest decrease in NO production rate (96% ± 1.3 activity loss at 500 μM ONOO
−
) and no activity was restored by excess BH
4
. In contrast, O
2
−.
induced a significant decrease (90% ± 1.2 activity loss at 500 μM O
2
−.
), however excess BH
4
restored the iNOS activity back to 69% ± 5.6.O
2
−.
exposure enhanced O
2
−.
production from iNOS (up to 155% ± 0.72 at 50 μM O
2
−.
), while ONOO
−
at higher concentrations (>20μM) reduced O
2
−.
production (10% ± 3.2 decrease at 50 μM ONOO
−
). We also found that incubation with ONOO
−
and O
2
−.
induced iNOS monomerization. In conclusion, both ONOO
−
and O
2
−.
decrease iNOS NO production in a dose dependent manner. Adding excess BH
4
only partially restore the loss of NO production induced by ONOO
−
, but almost completely restore the loss of NO production induced by O
2
−..
Therefore, O
2
−.
promotes the uncoupling of iNOS and elevates O
2
−.
production by oxidizing the protein bound BH
4
with subsequent formation of NOS monomer in a reversible fashion. Conversely, ONOO
−
induces irreversible enzyme inactivation and decreases both NO and O
2
−.
production. Although oxidation of BH
4
is involved in the observed ONOO
−
induced loss of iNOS activity, there are other causes, including oxidation of critical amino acid residues.
Abstract 3127: Pulmonary Valve Replacement in Tetralogy of Fallot: Impact on Survival and Freedom from Ventricular Tachycardia
Authors: Harrild David M , Geva Tal , Pigula Frank , Cecchin Frank , Berul Charles I , Gauvreau Kimberlee , Walsh Edward P
Published: July 2021

Background
: Pulmonary regurgitation (PR) in repaired tetralogy of Fallot (TOF) is associated with right ventricular (RV) dilation and dysfunction as well as arrhythmia. Pulmonary valve replacement (PVR) may prevent the development of these late complications. This retrospective study tests the hypothesis that PVR improves survival and freedom from ventricular tachycardia (VT) in patients with TOF.

Methods
: Enrolled patients had TOF with PVR for RV dilation from PR. Referral for PVR was largely based on symptoms. Controls (TOF patients with RV dilation
but no PVR
), were matched by age (± 2 years) and QRS duration (± 30 msec). There were 77 case/control pairs. Pairs did not differ significantly for age, repair type, decade of TOF repair, age at TOF repair, or presence of pre-PVR VT. Primary outcome events were death and VT. Events were recorded only if they occurred while both case/control were actively followed. Total duration of post-PVR follow-up was 172 patient years per group (median 1.4y, 0.01 – 13.2). PVRs were performed between 1990 and 2005 at median age 21y (6 –57).

Results:
The change in QRS duration did not differ significantly between the two groups (p = 0.43). Other results are summarized in the table

and figure

below.

Conclusion:
In this cohort of patients with repaired TOF, late PVR for symptomatic PR/RV dilation did not lead to reduced incidence of VT and/or death.
Abstract 3135: Impact Of PCI On The Clinical Burden Of Atherothrombotic Disease. An Analysis From The NHLBI Dynamic Registry
Authors: Laskey Warren K , Selzer Faith , Mokwe Evan , Holmes David , King Spencer , Cohen Howard , Slater James , Tanguay Jean-Francois , Holper Elizabeth , Williams David , Detre Katherine
Published: July 2021

Introduction
. The addition of percutaneous coronary intervention (PCI) to the treatment options for patients with atherothrombotic (AT) coronary heart disease (CHD) has resulted in considerable debate regarding its overall clinical benefit. Although rates of “hard” clinical endpoints have been used as measures of both clinical outcome and disease burden, a comprehensive, clinically relevant measure of disease burden in the general population of patients undergoing PCI is lacking.

Hypothesis
. A comprehensive measure of AT clinical burden in patients undergoing PCI can be used to detect the qualitative and quantitative impact of PCI over time.

Methods
. Four distinct cohorts (Waves) of ~ 2,000 patients each participating in the NHLBI Dynamic Registry beginning in 1997 (Wave 1) and terminating in 2005 (Wave 4) and surviving to hospital discharge comprise the study population (n= 7,750). A composite clincally relevant measure of AT disease burden over the year following PCI was defined as: any death, myocardial infarction (MI), hospitalization for recurrent angina (A) or congestive heart failure (HF), stroke, any repeat PCI or coronary bypass surgery. Cumulative event rates, expressed as the presence of any of the above-cited components by one year, were calculated using Kaplan-Meier statistics. Comparison of rates across Waves was accomplished using Cochran- Mantel-Haenszel method.

Results.
see Table

Exclusion of patients requiring PCI for restenosis did not substantially change the overall AT burden.

Conclusion.
There was a statistically significant decrease in AT disease burden over the time studied. However, the burden of disease in patients undergoing PCI remains substantial for 25% of patients. This measure of AT burden may be of clinical value in assessing the contribution of PCI to patient outcomes and strongly supports more comprehensive treatment strategies for patients following PCI.

Component and composite rates at one year
Abstract 3138: Impact of “Off Label” Utilization of Drug-Eluting Stents on Clinical Outcomes in Patients Undergoing Percutaneous Coronary Intervention
Authors: Roy Probal , Buch Ashesh N , Javaid Aamir , Okabe Teruo , Raya Vikram , Slottow Tina L Pinto , Steinberg Daniel H , Smith Kimberly , Xue Zhenyi , Satler Lowell F , Kent Kenneth M , Suddath William O , Pichard Augusto D , Lindsay Joseph , Waksman Ron
Published: July 2021

Background:
The utilization of drug-eluting stents (DES) in “real world” practice has deviated substantially from Food and Drug Administration (FDA) approved indications. The outcomes of patients undergoing intracoronary DES implantation (versus BMS) for non-FDA approved indications has not been determined.

Methods
: The clinical outcomes of 546 patients undergoing DES implantation for ≥1 non-FDA approved (“Off label”) indication after device approval were assessed. This group was then compared to 546 propensity-matched patients receiving BMS prior to DES approval for the same indications. The primary endpoint was major adverse cardiac events [MACE; death-all cause, non-fatal Q-wave MI and target vessel revascularization (TVR)] at 12 months.

Results:
Baseline clinical and procedural characteristics were well matched. Patients in the BMS group were more likely to be treated with larger diameter and shorter stents. Though both in-hospital and 30-day all-cause mortality was greater in the DES group, there was no significant difference in cardiac death at both time points. At 30 days all other clinical outcomes were comparable. At 12 months MACE was significantly reduced in the DES group (27.8% vs. 21.4% p=0.014) driven by reductions in repeat revascularization [target lesion revascularization (TLR): 16.4% vs. 7.8% p<0.001, TVR: 20.2% vs.13.1% p<0.003]. There was no significant increase in death and non-fatal Q-wave MI with DES.

Conclusions:
The utilization of DES for non-FDA approved indications proved to be efficacious and safe when compared to a propensity-matched BMS cohort. These findings support broadening the current FDA indications for DES use.
Abstract 3153: Adipocyte Dysfunction Contributes to Metabolic Abnormalities in Acute Decompensated Heart Failure
Authors: Schulze P Christian , Biolo Andreia , Blalog Joshua , Fish Mark , Siwik Deborah , Colucci Wilson S
Published: July 2021

Patients with chronic heart failure (HF) develop metabolic abnormalities including a catabolic state, weight loss and cachexia that are associated with adipocyte dysregulation. Several factors, such as inflammatory cytokines and neurohormones, that regulate adipocytes are known to be elevated in ADHF. Therefore, we hypothesized that in acute decompensation (ADHF) there is marked dysregulation of adipocyte function as reflected by circulating adipocytokines including visfatin, a recently described adipocytokine.

Methods:
Plasma was obtained from 41 patients with ADHF (EF 27 ± 14, BMI 32 ± 6), 25 patients with chronic stable HF (EF 27 ± 18, BMI 28 ± 5), and 21 control subjects (EF 63 ± 3, BMI 31 ± 6) without HF. Levels of NT-proBNP, visfatin, adiponectin, resistin, leptin, insulin, IGF-1 and TNFα were measured by ELISA. Insulin resistance was assessed by HOMA-IR quotient.

Results:
NT-proBNP was 330 ± 28 fmol/mL in control (Con) patients, elevated to 704 ± 86 fmol/mL in chronic HF and elevated further to 1774 ± 206 fmol/mL in ADHF. Adiponectin was 14.9 ± 3 ng/mL in Con, increased to 28.9 ± 5.7 (p < 0.05) in stable HF, and increased further to 42.9 ± 2.8 ng/mL in ADHF (p < 0.05). Likewise, visfatin was 16.9 ± 3.5 ng/mL in Con, increased to 43.4 ± 9.5 (p < 0.05) in stable HF, and increased further to 79.9 ± 4.6 ng/mL ng/mL in ADHF (p < 0.05). Leptin and resistin were not elevated in chronic stable HF, whereas in ADHF, leptin (9.6 ± 1.0 vs 3.7 ± 0.6 ng/mL; p < 0.0001) and resistin (11.6 ± 1.3 vs 5.7 ± 0.9 ng/mL; p < 0.01) were both elevated compared to Con. Insulin resistance was present in chronic stable HF (24.5 ± 2.2 μU/mL*mg/dL) and increased further in ADHF (32.9 ± 2.0 vs; p < 0.001 vs. Con). In contrast, IGF-1 or insulin were unchanged in the three groups. In patients with ADHF, visfatin, resistin and insulin resistance all correlated with TNFα (p < 0.05 for all).

Conclusion:
In ADHF there is marked dysregulation of adipocytes as evidenced by elevated blood levels of several adipocytokines, including adiponectin, visfatin, leptin and resistin, and paralleled by worsening insulin resistance. TNFα may contribute to both adipocyte dysregulation and insulin resistance. Metabolic dysfunction in ADHF is associated with elevated adipocytokines that have important effects on insulin signaling.
Abstract 3163: Association of Pre-PCI TIMI flow grade (TFG) with Subsequent Mortality in Patients Presenting with ST-Elevation Myocardial Infarction (STEMI)
Authors: Nguyen Michael C , Pinto Duane S , Hochberg Claudia , Almahameed Amjad , Pride Yuri , Abraham Jo Ellyn , Frederick Paul D , Murphy Sabina A , Gibson C M
Published: July 2021

Background:
Pre-procedural TIMI flow grade has been associated with mortality (both in-hospital and long-term) in patients (pts) undergoing percutaneous coronary intervention (PCI) following STEMI in randomized trials. This relationship has not been well characterized in a large heterogeneous real world population.

Methods:
A cohort of 8,133 patients presenting with STEMI in the National Registry of Myocardial Infarction (NRMI) was studied. Analysis of the relationship between pre-PCI TFG and in-hospital mortality was performed.

Results:
Of the 8133 patients, 6307 (77.5%) had TFG 0/1, 1178 (14.5%) had TFG 2, and 648 (8.0%) had TFG 3. Patients with TFG 0/1 before PCI (primary, rescue or facilitated) had an in-hospital mortality rate of 3.3% compared with TFG 2 of 1.6% and TFG 3 of 1.2% (
P
< 0.001). Pre-PCI TFG was associated with significant differences in mortality in all subgroups including age, gender, and location of infarct (see table

). Among pts with TFG 3 post PCI, mortality was still associated with pre-PCI TFG (pre-TFG 0/1 = 2.7%, pre-TFG 2 = 1.5%, TFG 3 = 1.2%,
P
= 0.002).

Conclusion:
Pre-PCI TFG is associated with in-hospital mortality in a heterogeneous group of real world patients presenting with STEMI treated with PCI, including those with TFG 3 following PCI.
Abstract 3167: Serum Activin A Level Is Associated With Infarct Size In Patients With Acute Myocardial Infarction Who Undergo Successful Primary Percutaneous Coronary Intervention
Authors: Miyoshi Toru , Hirohata Satoshi , Uesugi Tadahisa , Hirota Minoru , Ohnishi Hiromichi , Nogami Kunio , Kusachi Shozo , Ohe Tohru
Published: July 2021

PURPOSE:
Activin A, a member of the transforming growth factor-beta cytokine family, has been suggested to play a role in inflammation and have pleiotropic functions. We examined the alteration of serum activin A level in patients with ST-segment elevation myocardial infarction (STEMI) who received successful primary percutaneous coronary intervention (PCI) within 12 hours, and investigated whether serum activin A was associated with infarct size.

METHODS:
We examined 26 patients with STEMI, 20 consecutive stable angina pectoris (AP) patients and 20 normal subjects. In STEMI patients, blood samples were collected before PCI (day0) and days 1, 2, 7 and 14. Serum activin A level was measured by enzyme-linked immunoassay. Change of activin A between day 2 and day0 (delta 2d) was also examined. The serum levels of activin A were compared with infarct size, as indicated with peak CK.

RESULTS:
Patients with STEMI demonstrated significantly higher serum activin A level (before PCI) than control subjects and patients with AP (316±112, 369±153 and 569±272 pg/ml, p<0.001 and p=0.007, respectively). The activin A level was significantly elevated and peaked on day 0 and reduced on days 2, and then gradually increased until days 14. Log-transformed peak CK was significantly correlated with serum activin A level on day0 (r=0.55, p=0.004) and delta 2d (r=0.58, p=0.023). In stepwise analysis, serum activin A level (beta=0.37, p=0.022) as well as age, culprit lesion (LAD) and smoking was an independent predictor of peak CK.

CONCLUSIONS:
The findings suggest that serum activin A level was elevated in STEMI and it may be associated with infarct size in STEMI patients.
Abstract 3172: Impact of Prosthesis-Patient Mismatch on Long-Term Survival After Aortic Valve Replacement
Authors: Mohty Dania , Dumesnil Jean G. , Echahidi Najmeddine , Mathieu Patrick , Dagenais François , Voisine Pierre , Pibarot Philippe
Published: July 2021

Background:
We recently reported that Prosthesis-Patient Mismatch (PPM) is an independent predictor of operative mortality in patients undergoing aortic valve replacement (AVR). The objective of this study was to evaluate the impact of PPM on late postoperative survival.

Methods and Results:
Between 1992 and 2005, 2653 patients (age: 68±10 years; 61% of males) underwent AVR in our institution. Patients who died at the time of operation or within 30 days were excluded from this study. The projected indexed effective orifice area (EOAi) was derived from the published normal in vivo EOA values for each model and size of prosthesis and PPM was classified as severe if the EOAi was ≤0.65 cm
2
/m
2
, moderate if it was > 0.65 cm
2
/m
2
and ≤ 0.85 cm
2
/m
2
, or not clinically significant if >0.85 cm
2
/m
2
. PPM was severe in 40 patients (2%), moderate in 797 (31%), and not significant in 1739 (67%). Patients with severe PPM had higher proportion of female gender (67% vs. 38%; P=0.0002) and hypertension (68% vs. 55%, p=0.02) and larger body surface (1.86±0.25 vs. 1.77±0.20, p=0.02). For patients with severe PPM, 5-year survival rate (74±8%) and 10-year survival rate (40±10%) were significantly (p=0.008) less than for patients with moderate PPM (5-yr: 81±2% and 10-yr: 57±3%) or no significant PPM (5-yr: 84±1% and 10-yr: 61±2%). On multivariate analysis after adjustment for other predictors of outcome, severe PPM was associated with increased overall mortality (Hazard ratio 1.38, [95% Confidence Interval 1.04 –1.75]; (p=0.02)

Conclusion:
In our previous study, we reported that severe PPM is a powerful risk factor for operative mortality. The results of the present study now suggest that severe PPM is also an independent predictor of long-term mortality. Hence, for the patients who are identified to be at risk of severe PPM at the time of operation, every effort should be made to implant a prosthesis with a larger EOA.

Funded by:
Canadian Institutes of Health Research
Abstract 3179: Intraoperative Transoesophageal Echocardiographic Predictors of Recurrent Aortic Regurgitation after Aortic Valve Repair.
Authors: le Polain de Waroux Jean-Benoit , Pouleur Anne-Catherine , Goffinet Céline , Vancraeynest David , Gerber Bernhard L , Pasquet Agnes , El khoury Gébrine , Noirhomme Phillippe , Vanoverschelde Jean-Louis
Published: July 2021

Background.
Surgical valve repair for aortic regurgitation (AR) has significant advantages over valve replacement, but little is known about the mechanisms of its failure. This echocardiographic study examines the intraoperative features associated with “late failure” of valve repair, eventually necessitating reoperation.

Method.
Intraoperative transesophageal echocardiography (TEE) after cardiopulmonary bypass was performed in 168 consecutive patients (pts) undergoing valve repair for AR over a 10-year period. From this cohort, we carefully reviewed all clinical, pre-operative, intraoperative and follow-up TEE data of 62 pts (group A, 53 ± 13 years) with no or trivial AR at follow-up and 31 pts (group B, 46 ± 15 years) with recurrent severe AR at follow-up of whom 17 needed a re-operation. In these pts, echocardiography identified the cause of repair failure as rupture of a pericardial patch in 2 pts, residual cusp prolapse in 18 pts, restrictive cusp motion in 8 pts, aortic dissection in 2 pts and endocarditis in the remaining pt.

Results.
Pre-operatively, both groups were similar for aortic root dimensions and incidence of bicuspid valve (39 ± 4 % vs 35 ± 5 %, χ
2
= 0.4). Marfan disease and restrictive cusp motion or endocarditis were more frequent in group B than in group A (16 ± 4% vs 0% and 48 ± 5% vs 14 ± 3%, χ
2
= 0.001). After cardiopulmonary bypass, the coaptation length was shorter (2.2 ± 1.5 vs. 6.8 ± 2.8 mm, p<0.001), the level of coaptation (relative to the annulus) was lower (0.0 ± 4.4 vs 6.9 ± 3.9 mm, p<0.001), the aortic annulus was larger (27 ± 5 vs 22 ± 4 mm, p<0.001) and the vena contracta was wider (2.4 ± 1.0 vs 0.05 ± 0.9 mm, p<0.001) in group B than in group A pts. Interestingly, 13/18 (72%) pts in whom recurrent AR was due to a cusp prolapse, had eccentric AR jets before leaving the operating room. With multivariate analysis, only a coaptation length < 5 mm (OR=13.1, 95%CI [2.4; 70.5] p=0.003), the presence of an eccentric jet (OR=8.02, 95%CI [2.1; 30.4] p=0.002) and the level of coaptation relative to the aortic annulus (OR=4.7, 95%CI [1.0; 21.6] p=0.049) were found to independently predict late AR recurrence.

Conclusion.
Our results demonstrate that intraoperative TEE can be used to identify pts undergoing AR repair who are at increased risk for late repair failure.
Abstract 3191: Experimental Validation Using Radiolabeled Microspheres of Absolute Quantitation of Regional Myocardial Blood Flow (MBF) Using Dynamic Rb-82 Positron Emission Tomography (PET)
Authors: El Fakhri Georges , Mekkaoui Choukri , Sitek Arkadiusz , Dione Donald P , Carson Richard E , Brennan Matthew , Di Carli Marcelo F , Sinusas Albert J
Published: July 2021

Absolute quantitation of MBF with dynamic Rb-82 PET has great potential in the assessment of the extent and severity of ischemia in patients with suspected coronary artery disease, particularly at centers that lack access to a cyclotron, but requires validation of MBF estimation.

METHODS: In order to validate our automated Rb-82 PET MBF quantitation based on generalized factor and compartment analyses (GFADS), we compared rest/stress regional Rb-82 MBF to reference MBF measured with radiolabeled microspheres (MS) in 6 dogs before and after creation of a critical LAD stenosis. High resolution dynamic Rb-82 PET acquisitions were performed on a Siemens HRRT in 3D listmode at rest and during adenosine stress in conjunction with injection of MS. Studies were rebinned into 24 5-sec, 6 10-sec, and 4 20-sec frames, and reconstructed using OSEM, compensating for scatter, randoms, attenuation and resolution. Hearts were cut into 5 mm slices (8 radial segments per slice). Myocardial segments were re-mapped to match the 17 segments of the standard polar map. Left and right ventricle input functions were automatically computed using GFADS. LV input was validated with on-line measurements of arterial activity. Polar maps of MBF (K1, ml/g/min) and coronary flow reserve (CFR) were computed using a 2-compartment kinetic model yielding 34 segments at rest and stress for each dog, that were remapped into apical, mid and basal ischemic and non-ischemic territories.

RESULTS: MBF (uncorrected by RPP) derived from dynamic PET were in reasonable agreement with MS values at rest: MBF (PET) = 0.38 x MS + 0.39, r= 0.70, and in good agreement with MS values at stress: MBF(PET) = 0.48 x MS + 0.22; r=0.86. Regional CFR derived from dynamic PET was also in good agreement with MS values in the normal LCX territory (PET:1.44Â±0.17 vs MS:1.53Â±0.14) as well as in the LAD territory where a stenosis was created (1.07Â±0.18 vs. 1.17Â±0.16). PET and MS CFR values correlated well over the range of 0.51–2.37: CFR(PET) = 0.796 x MS + 0.421; r=0.940.

CONCLUSION: Absolute quantification of MBF and CFR can be obtained from dynamic rest/stress Rb-82 PET using a fully automated GFADS approach which was validated in experimental animals using MS flow and should permit rapid determination of absolute MBF in patients.
Abstract 434: A New Drug Delivery System Using Fibronectin-vegf Fusion Is More Effective And Harmless Than Vegf Alone For The Therapeutic Neovascularization
Authors: inoue Takahiro , Egashira Kensuke , Ide Tomomi , Tsutsumi Takaki , Monden Yoshiya , Kubo Mitsuki , Kitajima Takashi , Kubota Toru , Sunagawa Kenji
Published: July 2021

Background:

Recent clinical trials for therapeutic angiogenesis reported limited efficacy. To overcome these limitations, we developed a fusion protein of fibronectin (Fn) and VEGF (Fn-VEGF), with high collagen affinity, binding to extracellular matrix of ischemic area. We hypothesized that controlled delivery of VEGF using this protein is useful for therapeutic angiogenesis.

Methods and Results:

We examined biological effects of Fn-VEGF on human endothelial cells cultured on collagen coated dishes, and found that a single administration of Fn-VEGF caused sustained proliferation at least for a week. We then produced hindlimb ischemia in mice, and injected PBS, VEGF, Fn, or Fn-VEGF (10 μg/day) into ischemic muscles. Fn-VEGF retained in the injected area for 5 days, whereas VEGF alone rapidly disappeared from the injected area after 3 hours. Moreover, injection of Fn-VEGF enhanced recovery of blood perfusion of ischemic limb, the degrees of which is greater than those afforded by VEGF (Fn-VEGF 94.1 ±12.3 vs VEGF 72.3 ±9.2 %, p<0.01). Importantly, Fn-VEGF enhanced limb salvage rate better than VEGF, and high dose administration of VEGF worsened limb ischemia up to complete amputation, whereas high dose Fn-VEGF (40 μg/day) represented a proper effect (Figure

). Moreover, as well as VEGF, Fn-VEGF has also capacity making mononuclear cells to endothelial progenitor cells, and induced proper degree of angiogenesis from endothelial cells.

Conclusions:

Injection of Fn-VEGF was more effective and harmless than VEGF, suggesting that controlled delivery of VEGF using this protein may be a clinically useful and feasible strategy for next-generation neovascularization.
Abstract 436: The Fat1 Cadherin Intracellular Domain Interacts with Atrophin Proteins and Recruits Robust Transcription Activity
Authors: Hou Rong , Sibinga Nicholas
Published: July 2021

Background: We recently reported that the atypical cadherin Fat1 is strongly induced after arterial injury, inhibits growth and promotes migration of vascular smooth muscle cells (VSMCs), and can undergo cleavage, with subsequent translocation of its intracellular domain (Fat1IC) to the cell nucleus. In Drosophila, dFat and Atrophin, a nuclear receptor transcriptional corepressor implicated in the control of cell polarity and migration, have been linked by both physical and genetic interaction. Together, these findings suggest an important integrative role for Fat1 in active vascular remodeling, and raise the possibility that some Fat1 effects are mediated from the nucleus via interaction with transcriptional regulators.

Objectives, methods, findings: We hypothesized that the interaction of mammalian Fat1IC with nuclear proteins, such as the mammalian Atrophin homologues atro-1 and atro-2, might contribute to the phenotypic effects of Fat1 on VSMC activation. To test for such interactions, we performed co-immunoprecipitation and Western analysis, identified a physical interaction of Fat1 with atro-1 and atro-2, and mapped necessary Fat1IC sequences to a discrete domain. Immunocytochemical staining showed partial co-localization of Fat1 and atro-1 and -2 in the nucleoplasm. In mammalian two-hybrid assays, surprisingly, tethering of the Fat1IC to DNA yielded very robust transcriptional activation, not repression. This activity was augmented by COUP-TFs, orphan nuclear receptor transcription factors known to associate with atrophins and implicated in both angiogenesis and cardiac development, but not previously linked to Fat1. The biological relevance of these interactions is further supported by quantitative PCR analysis that showed induction of both atro-1 and atro-2 mRNAs after vascular injury, similar to the pattern we identified for Fat1.

Conclusion: The biological significance and molecular functions of the multiple cadherin superfamily proteins expressed in VSMCs are not well understood. Our studies demonstrate the physical and functional interaction of the Fat1IC with multiple nuclear proteins involved in transcriptional regulation, and point to novel pathways by which Fat1 may affect VSMC growth and migration.
Abstract 3202: Gender Differences Among Patients with Acute Coronary Syndromes Undergoing Percutaneous Coronary Intervention in the ACC/NCDR PCI Registry
Authors: Akhter Nausheen , Milford-Beland Sarah , Roe Matthew T , Shroff Adhir R
Published: July 2021

Background
: Cardiovascular disease is the leading cause of death in women. Prior studies have demonstrated gender disparities in the management and outcomes of women with acute coronary syndromes (ACS).

Objectives
: We sought to explore if gender differences exist in a patient population who present with ACS and have a percutaneous coronary intervention (PCI) during hospitalization in a large, contemporary national PCI registry, the American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR).

Methods
: We analyzed ACS patients who had a PCI in the ACC-NCDR PCI registry from January 1, 2004 to March 30, 2006. Clinical characteristics, procedural and clinical outcomes, and concomitant medical therapies were compared between men and women according to ACS status: unstable angina (UA)/non-ST elevation MI (NSTEMI) and ST elevation MI (STEMI).

Results
: Of 199,690 patients with ACS who underwent PCI, women more often presented with unstable angina (57.7% vs. 53.9%), equally with NSTEMI (24.2% vs. 23.6%), and less often with STEMI (18.1% vs. 22.6%) compared with men. In both ACS categories, women were older and had a higher incidence of diabetes (insulin or non-insulin dependent), HTN, PVD, CVA, past and current CHF and renal failure. There was also a higher incidence of cardiogenic shock in women among the STEMI population. The use of drug eluting stents was similar among women and men, but women were less likely to receive aspirin, GP IIb-IIIa inhibitors, and discharge aspirin and statins compared with men. While the adjusted rate of in-hospital mortality was similar among women and men, women had higher rates of peri-procedural complications, including more cardiogenic shock, CHF, bleeding and vascular complications. Rates of subacute stent thrombosis were similar between genders.

Conclusions
: Women with ACS who underwent PCI were older and more likely to have comorbidities compared with men, and were more likely to have procedural complications. Whether these differences were related to the observed differences in a number of evidence-based medications or clinical characteristics among women vs. men will require further study. Adjusted rate of in-hospital mortality was similar among women and men.
Abstract 3204: Implications of Preoperative thienopyridine Use in Patients With non-ST Elevation Acute Coronary Syndrome Undergoing Coronary Artery Bypass Surgery: One year Results From the ACUITY Trial
Authors: Ebrahimi Ramin , Feit Frederick , Manoukian Steven V , Lincoff A. Micheal , Dyke Cornelius , Gersh Bernard , Mehran Roxana , Moses Jeffrey , Stone Gregg W
Published: July 2021

Thienopyridine administration has a class Ia recommendation in patients with non-ST elevation acute coronary syndromes (ACS). Despite this many physicians withhold this treatment until after angiography because of concerns over the minority of patients who may require coronary artery bypass surgery (CABG). We sought to evaluate the one year composite ischemic outcomes (death, myocardial infarction, revascularization) in ACS patients requiring CABG based on thienopyridine exposure and timing of CABG.

Methods:
In the ACUITY trial, thienopyridine administration and timing was left to investigators’ discretion. In the subset of patients requiring CABG, the one year composite ischemic outcome was compared in those not exposed to thienopyridines (group A), those who received thienopyridine and went to CABG ≤120 hours from the last dose (group B) and those who received thienopyridine and went to CABG >120 hours after the last dose (group C). Major bleeding was defined based on ACUITY definitions.

Results:
CABG was performed in 1539 (11.1%) patients. There were no significant differences in baseline characteristics among the three groups. Mean time from angiography to CABG, major bleeding, and 1-year composite ischemia are presented in the table

below.

Conclusions:
Based on our analysis of ACS patients undergoing CABG in the ACUITY trial, those who received thienopyridine preoperatively and went to CABG >120 hours from the last dose had improved one year composite ischemic outcomes compared to those not exposed or those who received thienopyridine and went to CABG ≤120 hours after the last dose.
Abstract 3207: Role of Ischemic Preconditioning and Inflammatory Response in the Development of Malignant Ventricular Arrhythmias after Reperfused Acute Myocardial Infarction
Authors: Kaneko Hidehiro , Anzai Toshihisa , Naito Kotaro , Ueno Koji , Jo Yusuke , Takahashi Toshiyuki , Kawamura Akio , Yoshikawa Tsutomu , Ogawa Satoshi
Published: July 2021

Background:
Malignant ventricular arrhythmias, such as sustained ventricular tachycardia and ventricular fibrillation (VT/VF), are fatal complications after acute myocardial infarction (MI) even in the era of reperfusion therapies. We sought to clarify the determinants of VT/VF after reperfused MI.

Methods:
A total of 528 consecutive acute MI patients, who were treated with primary percutaneous coronary intervention, were divided into 2 groups according to the presence or absence of VT/VF during hospitalization. Serum C-reactive protein (CRP) level and peripheral white blood cell (WBC) count were serially measured for every 24 hours. As a substudy, left ventricular (LV) function and long-term clinical outcome were compared between patients with early (>48 hours after the onset) and late VT/VF (>48 hours).

Results:
VT/VF was observed in 58 patients (11%). Prior MI and anterior MI are more common in patients with VT/VF than those without. Prevalence of preinfarction angina was less in patients with VT/VF than those without. Peak CRP (14.7±10.1 vs. 8.8±7.1 mg/dl, p< 0.0001), WBC on admission (12833±3513 vs. 10906±4771 /mm
3
, p=0.03) and maximum WBC (14808±5335 vs. 12531±4348 /mm
3
, p=0.009) were higher in patients with VT/VF than those without. Multivariate analysis revealed that prior MI (RR=4.57, p=0.02), absence of preinfarction angina (RR=2.44, p=0.02) and peak serum CRP ≥10 mg/dl (RR=3.37, p=0.003) were independent determinants of VT/VF. Early VT/VF was observed in 49 patients, while late VT/VF in 9 patients. Prevalence of prior MI, preinfarction angina or peak CRP ≥10mg/dl was comparable between early and late VT/VF. LV end-diastolic and end-systolic dimensions are greater in patients with late VT/VF than those with early VT/VF (p< 0.05). Incidence of readmission for heart failure and sudden cardiac death tended to be higher in patients with late VT/VF than those with early VT/VF.

Conclusions:
VT/VF after reperfused acute MI was associated with prior history of MI, absence of preinfarction angina and increased inflammatory markers. VT/VF occurred in late phase was related to depressed LV function. Lack of ischemic preconditioning, enhanced inflammatory response and subsequent LV remodeling could contribute to the development of VT/VF after MI.
Abstract 3215: Effects of Selective and Non-Selective Beta-Blockers on Cardiovascular Risk in Patients with Heart Failure or Acute Coronary Syndrome: a Meta-Analysis.
Authors: de Peuter Olav R , Lussana Federico , Kamphuisen Pieter W
Published: July 2021

Background:
Guidelines generally recommend the use of beta-blockers in patients with heart failure (HF) and acute coronary syndrome (ACS). It has recently been suggested that non-selective beta-blockers were more effective than selective beta-blockers in HF. However, a better efficacy of different beta-blockers, specifically analyzing total and cardiovascular (CV) mortality and morbidity, in patients with HF or ACS is unclear.

Methods:
We performed a meta-analysis of randomized controlled trials (RCTs) through Medline, EMBASE, and Cochrane Library databases to identify RCTs comparing selective or non-selective beta-blockers with placebo (29 studies, 31,856 patients), or directly comparing the two different beta-blockers (5 studies, 3,733 patients). Studies were selected using a priori defined criteria and data on study characteristics, study quality and outcomes were abstracted. All included studies had (cardiovascular) mortality as primary or secondary endpoint.

Results:
In patients with HF non-selective beta-blockers were associated with a reduction in total mortality (RR 0.75, 95%CI 0.61–0.92), and with a non significant decrease in CV mortality. Selective beta-blockers decreased total and CV mortality (RR 0.76, 0.68–0.84 and RR 0.78, 0.66–0.92, respectively). In patients with ACS non-selective beta-blockers were associated with a significant decrease in total mortality (RR 0.73, 0.64–0.82), CV mortality (RR 0.69, 0.60–0.80) and CV morbidity. Selective beta-blockers however had no effect on total mortality (RR 0.88, 0.68–1.15) or CV mortality (RR 0.89, 0.69–1.15). In HF, direct comparison showed a significantly decreased mortality (RR 0.86, 0.78–0.94) for non-selective beta-blockers compared to selective beta-blockers. For ACS, only one study directly compared different beta-blockers.

Conclusions:
In patients with HF, selective and non-selective beta-blockers seem equally effective in reducing mortality. In patients with ACS, selective beta-blockers had no influence on total and cardiovascular mortality, in contrast to non-selective beta-blockers. This meta-analysis suggests that patients with ACS should specifically be treated with non-selective beta-blockers to reduce total and cardiovascular mortality.