bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2234: Self-care And Quality Of Life In Patients With Heart Failure
Authors: Chiaranai Chantira , Salyer Jeanne
Published: July 2021

Purpose:
Although it is well-known that self-care (SC) reduces the frequency of hospital admissions and exacerbations, and enhances quality of life (QOL) in heart failure patients, little is known about SC in this population. The study purpose was to examine relationships among selected individual characteristics (demographics, severity of illness, co-morbidities, and social support), SC strategies, and QOL using Reigel’s Model of Self Care in Patients with Heart Failure as the guiding framework.

Method:
114 subjects were recruited to participate in this descriptive correlational study. SC was measured using the
Self-Care of Heart Failure Index
, which measures self-care maintenance (SC-Mt), self-care management (SC-Mn), and self-care self-confidence (SC-Sc). QOL was measured using a disease-specific instrument, the
Minnesota Living with Heart Failure Questionnaire
, and a generic instrument, the
Short-Form Health Survey
characterizing physical and mental-emotional functioning. Multiple regression analysis was used to identify predictors of QOL.

Findings:
98 subjects (age = 56.7 years; 53.8% male; 49.5% Caucasian) completed and returned mailed questionnaires. Multiple regression analyses demonstrated that better disease-specific QOL was predicted by being less likely to try SC-Mn strategies (β = .325;
p
= 0.003), better SC-Sc (β = −.251;
p
= 0.012), better NYHA functional class (β = .246;
p
= 0.008), and less co-morbidity (β = .236;
p
= 0.014) (R
2
= .334; F = 7.269,
p
= 0.000). Better generic QOL (physical functioning) was predicted by better NYHA functional class (β = −.309; p = 0.001), better SC-Mt (β = .205; p = 0.037), better SC-Sc (β = .296;
p
= 0.003), and being less likely to try SC-Mn strategies (β = −.165;
p
= 0.000) (R
2
= .361; F = 9.602,
p
= 0.000). Better generic QOL (mental-emotional functioning) was predicted by better NYHA functional class (β = −.229; p = 0.024), and being men (β = −.204; p = .047) (R
2
= .277; F = 4.548,
p
= 0.000).

Discussion:
Findings suggest that better QOL is influenced by gender (male), better NYHA functional class, less co-morbidity, and better use of SC strategies. Exploring patient decision-making can assist nurses in identifying how to improve decision-making performance and enhance QOL.
Abstract 2242: Very High Resolution Near Field Imaging of Ablation with a Newly-Developed Forward-Looking Catheter Mounted Microlinear Intracardiac Imaging Array
Authors: Sahn David J , Shung K. Kirk , Cannata Jonathan , Stephens Douglas N , Chia Raymond , Chen Peter , Thomenius Kai , Dentinger Aaron , Ashraf Muhammad , O’Donnell Matthew , Mahajan Aman , Shivkumar Kalyanam
Published: July 2021

Background:
We have developed the first forward-looking highly steerable intracardiac echo probe developed for ultrasound visualization of ablation. It is a 24-element forward-looking microlinear array on a 9 Fr catheter that has additional electrodes so it can be localized compared to separate ablation catheters through electrofield navigation by NavX.

Methods:
In 4 studies of closed-chest pigs, we have imaged ablation locations in the right atrium and the isthmus and on the right side of the septum and at the right ventricular apex, and also imaged across the septum at ablations in the left ventricle along the septum with this device.

Results:
Images at 150–170 frames/sec at 12–15 MHz give very high detail of the changes occurring during ablation, including liquefaction, heating changes, brightening and thickening of tissue, and thrombus formation in the adjacent region in unheparinized pigs. The devices are well enough shielded from RF energy that there is little interference, and yet an ablation is being performed. A catheter tip artifact makes it easy to see the actual location of the ablation catheter tip with the microlinear array. Tissue Doppler/strain rate imaging also yields the possibility of determining mechanical changes occurring in ablation where brightening of tissue associated with stiffening diminished mechanical strain deformations in ablated lesions, especially in the ventricles.

Conclusions:
This new technology provides a new method for guidance and, more importantly, a method for understanding the changes that occur with RF ablations in experimental animals and, eventually, in patients.
Abstract 2243: Real-Time Computed Tomography (RT-CT) for Guidance of Catheter Navigation, Transseptal Puncture and Anatomically Targeted Radiofrequency Ablation
Authors: Dickfeld Timm , Engelhardt Martin , Read Katrina , Kocher Christopher , Akella Jagan , Johnson Anthony , Peters Robert , Saba Magdi , Shorosfsky Stephen , Fleiter Thorsten
Published: July 2021

Background: Recent ablation strategies for complex arrhythmias such as atrial fibrillation or ischemic ventricular tachycardia are increasingly based on anatomic considerations. While fluoroscopy and 3D-mapping systems are widely used to guide these ablations, they are limited by poor soft tissue visualization and the lack of real-time anatomic data. Therefore, this study sought to evaluate if real-time computed tomography (RT-CT) could overcome these limitations and guide catheter navigation, transseptal puncture and anatomically targeted ablation.

Methods: Catheter real-time guidance was assessed in 5 swine (40kg) using a 40-slice RT-CT. First, right/left heart catheterization was performed from the femoral vein and artery with the goal to access all cardiac chambers and the great cardiac vessels. Second, transseptal puncture was attempted with targeted ablations at pre-specified locations at the left lateral wall. Third, targeted ablation at the pulmonary vein (PV) orifice and repeat ablations at the right lateral wall were created to assess accuracy and precision, respectively. Fourth, creation of a straight ventricular four-point line was attempted. Necropsy was performed to assess possible complications and to compare the location of the ablation sites with the CT images.

Results: Catheter navigation was performed safely from the femoral vein to the pulmonary artery and the femoral artery to the left ventricle. Misguided catheters to the renal vein, jugular vein, and carotid artery were correctly identified and removed. Transseptal puncture using a Brocken-brough needle was successfully performed and confirmed with anatomically targeted ablations at the left lateral atrial wall. Accuracy as assessed by PV ablations was in the range of 1–3mm. Repeat ablations in the right atrial wall revealed a precision of 2–3mm. Maximum deviation from a straight 4-point ventricular line was 2.8mm. No complications were seen at necropsy.

Conclusions: Catheter navigation (in all four cardiac chambers) as well as transseptal puncture can be performed guided exclusively by RT-CT. Anatomically targeted ablations can be created with good accuracy and precision under real-time guidance. This suggests a possible role of RT-CT to guide ablation procedures.
Abstract 2249: Overlap Between LQT3 and Brugada Syndrome: Clinical Features in a Common Mutation and Underlying Biophysical Mechanisms
Authors: Makita Naomasa , Behr Elijah , Shimizu Wataru , Horie Minoru , Crotti Lia , Itoh Hideki , Miyamoto Koji , Tsutsui Horoyuki , Schwartz Peter J , George Alfred L , Roden Dan M
Published: July 2021

Introduction:
Features of the Brugada syndrome (BrS) have been sporadically reported in type-3 long QT syndrome (LQT3). However, it is not clear whether such phenotypic overlap is determined by the biophysical properties of the mutant channel, or by other factors such as co-inherited genetic variations, gender, or ethnicity. To address this question, we report here the clinical features and biophysical properties of a single
SCN5A
mutation, E1784K, identified in multiple families of diverse ethnicities.

Methods and Results:
Among 37 LQT3 families (Asian 20, Caucasian 17) enrolled in 6 referral centers, 11 (30%) were carriers of E1784K, with a total of 33 mutation carriers (15 men, 18 women, 26±20 years; mean±SD). Two probands were the victims of sudden cardiac death. The LQT3 phenotype was highly penetrant: 30/33 (90.9%) mutation carriers had abnormally long QT intervals (carriers: QTc= 484±32 ms, n=33; non-carriers: QTc= 402±31 ms, n=21; p<0.001; mean±SD). In addition, 13/33 carriers (39%) showed sinus node dysfunction, and a diagnosis of BrS was established in 7/33. Four of five carriers exhibited coved-type ST elevation after class IC drug challenge. E1784K channels heterologously expressed in tsA201 cells in the presence of β
1
subunit showed late Na current characteristic of LQT3. In addition, E1784K displayed properties seen with other mutations sporadically reported to generate a mixed clinical phenotype (1795insD, ΔKPQ, ΔK1500): a large (−15.0 mV) negative shift in the voltage-dependence of inactivation (V
1/2
: wild type= −86.8±1.1 mV, n=25; E1784K= −101.8±1.3 mV, n=17; p<0.001, mean±SE), and a marked (7.5-fold) increase in flecainide affinity for rested channels (IC
50
: wild type= 150.3 μM, E1784K= 20.4 μM). These properties are not reported with T1304M, an LQT3 mutation that has not been associated with BrS.

Conclusions:
E1784K is a highly prevalent
SCN5A
mutation in different ethnicities, producing LQT3 as well as BrS and sinus node dysfunction.
In vitro
studies suggest that a negative shift of steady-state inactivation and enhanced channel inhibition at rest by class IC drugs identify LQT3 mutations that can generate such a mixed phenotype. Class IC drugs should be avoided in patients with LQT3 mutations displaying these behaviors.
Abstract 2260: Asymptomatic Patients with Severe Mitral Regurgitation and either Atrial Fibrillation or Pulmonary Hypertension Benefit from an Early Surgical Strategy
Authors: Chenot Fabien , Montant Patrick , Nsalampa Bertin Nkodia , Goffinet Céline , Pouleur Anne-Catherine , Le Polain De Waroux Jean-Benoît , Vancraeynest David , Pasquet Agnes , Gerber Bernhard , Vanoverschelde Jean-Louis
Published: July 2021

Background.
Degenerative mitral regurgitation (MR) is the second most frequent valvular heart disease in industrialized countries. Although there is consensus that valvular surgery should be advised in symptomatic patients (pts) with severe MR and in those with reduced LV function, there is persisting controversy regarding the optimal timing of intervention in asymptomatic pts with only atrial fibrillation or pulmonary hypertension, as shown by the corresponding class IIa recommendation in the recent guidelines.

Methods.
To test if asymptomatic pts with severe degenerative MR and either atrial fibrillation, pulmonary hypertension or both benefit from early surgery, the outcomes of 69 such pts (70 ± 12 years; 64% males) diagnosed by 2D-echo between 1990 and 2001 were analyzed. Pts with a LV ejection fraction below 60% or telesystolic diameter above 45 mm were not included. Group I comprised 46 pts undergoing mitral repair (within 3 months after diagnosis). Group II comprised 23 pts initially treated conservatively.

Results.
During follow-up, 3 Group II pts needed mitral surgery. Indications for surgery were according to class I current guidelines. Adjusted 10-year overall survival was better in Group I than in Group II pts (74 ± 8%, 11 ± 7%, p<0.0001). Similarly, adjusted 10-year cardiac event free survival, including the need for (redo) surgery was better in Group I than in Group II pts (72 ± 7%, 10 ± 10%, p<0.0001).

Conclusion.
Asymptomatic pts with severe MR complicated by either atrial fibrillation, pulmonary hypertension or both, clearly benefit from an early interventional strategy and should probably be operated on as soon as possible.
Abstract 2294: The Use of Myocardial Deformation Imaging Based on Ultrasonic Pixel Tracking to Identify Reversible Myocardial Dysfunction
Authors: Becker Michael , Lenzen Mithra , Stempel Katharina , Franke Andreas , Kelm Malte , Hoffmann Rainer
Published: July 2021

Objective.
Myocardial deformation imaging allows analysis of myocardial

Objective.
Myocardial deformation imaging allows analysis of myocardial viability in ischemic left ventricular dysfunction. This study evaluated the predictive value of myocardial deformation imaging for improvement in cardiac function after revascularization therapy in comparison to contrast-enhanced cardiac magnetic resonance imaging (ceMRI).

Methods and Results.
In 53 patients with ischemic left ventricular dysfunction, myocardial viability was assessed using pixel-tracking-derived myocardial deformation imaging and ceMRI to predict recovery of function at 9±2 months follow-up. For each left ventricular segment in a 16-segment model peak systolic radial strain was determined from parasternal 2D echocardiographic views using an automatic frame-by-frame tracking system of natural acoustic echocardiographic markers (EchoPAC, GE Ultrasound), and maximal thickness of myocardial tissue without late enhancement (LE) using ceMRI. Of 463 segments with abnormal baseline function, 227 showed regional recovery. Compared with segments showing functional improvement, those that failed to recover had lower radial strain (15.2±7.5 vs 22.6±6.3 %; p<0.001) and lower thickness without LE (5.2±2.9 vs 8.7±2.2 mm; p<0.001). Using a cut-off of 17.2 % for peak systolic radial strain, functional recovery could be predicted with high accuracy (specificity 85%, sensitivity 70%, area under the curve (AUC) 0.859, 95% CI: 0.825– 0.893). The predictive value of thickness without LE by ceMRI was similar at a cut-off of 8.2 mm (specificity 84%, sensitivity 70%, AUC 0.831, 95% CI: 0.793– 0.870).

Conclusion.
Myocardial deformation imaging based on frame-to-frame tracking of acoustic markers in 2D echocardiographic images is a powerful novel modality to identify reversible myocardial dysfunction.
Abstract 2322: Genetic Risk for Low HDL-cholesterol or High LDL-cholesterol Concentrations
Authors: Oguri Mitsutoshi , Kato Kimihiko , Yoshida Tetsuro , Hibino Takeshi , Yajima Kazuhiro , Fujimaki Tetsuo , Yokoi Kiyoshi , Matsuo Hitoshi , Warita Shunichiro , Segawa Tomonori , Watanabe Sachiro , Metoki Norifumi , Yoshida Hidemi , Satoh Kei , Aoyagi Yukitoshi , Yasunaga Akitomo , Park Hyuntae , Tanaka Masashi , Nozawa Yoshinori , Ichihara Sahoko , Yamada Yoshiji
Published: July 2021

Introduction.
A low serum concentration of HDL-cholesterol and a high serum concentration of LDL-cholesterol are risk factors for atherosclerosis. Our goal was to identify genetic variants that confer susceptibility to a low serum concentration of HDL-cholesterol (<1.04 mmol/L) or a high serum concentration of LDL-cholesterol (≥3.64 mmol/L).

Methods.
A total of 5213 individuals from two independent populations was examined: Subject panel A comprised 3794 individuals who either visited outpatient clinics of or were admitted to the participating hospitals because of various symptoms or for a health checkup; subject panel B comprised 1419 community-dwelling elderly individuals. The genotypes for 100 polymorphisms of 65 candidate genes were determined. Given the multiple comparisons of genotypes with these conditions, we adopted the criterion of a false discovery rate (FDR) of <0.05 for significant association in initial screening with the chi-square test.

Results.
Examination of genotype distributions by the chi-square test and subsequent multivariable logistic regression analysis with adjustment for age and sex revealed that six [−1131T→C, −3A→G, and 553G→T (Gly185Cys) of
APOA5
; −250G→A and −515C→T of
LIPC
; 13989A→G (Ile119Val) of
CYP3A4
] and three [4070C→T (Arg158Cys) and 3932T→C (Cys112Arg) of
APOE
; 190G→A (Val64Ile) of
CCR2
] polymorphisms were significantly (FDR < 0.05) associated with low HDL-cholesterol and high LDL-cholesterol, respectively, in subject panel A. To validate these associations, we examined the same polymorphisms in subject panel B. The three polymorphisms of
APOA5
and two polymorphisms of
APOE
were significantly associated with low HDL-cholesterol and high LDL-cholesterol, respectively. The serum concentrations of HDL-cholesterol and LDL-cholesterol differed significantly (
P
< 0.01, ANOVA) among genotypes of the corresponding polymorphisms in both subject panels. The polymorphisms of
APOA5
and
APOE
were each in linkage disequilibrium.

Conclusions.
Polymorphisms of
APOA5
and
APOE
are determinants of low HDL-cholesterol and high LDL-cholesterol, respectively. Genotyping of these polymorphisms may prove informative for prediction of the genetic risk for these conditions.
Abstract 342: Upregulation Of Mir-21 During Cardiac Hypertrophy Induces Down-regulation Of An Inhibitor Of The Ras-MAPK Pathway, Sprouty 2
Authors: Sayed Danish , He Minzhen , Chen Leng-Yi , Lypowy Jacqueline , Abdellatif Maha
Published: July 2021

MicroRNA (miRNA) are ~22 ribonucleotides-long, with a potential to recognize multiple mRNA targets guided by sequence complimentarity. This class of molecules is functionally versatile, with the capacity to specifically inhibit translation, as well as, induce mRNA degradation, through targeting the 3′ untranslated regions. The levels of individual miRNA vary under different developmental, biological, or pathological conditions, thus, implicating them in normal and pathological cellular attributes. We have previously reported a miRNA signature that distinguishes pressure-overload compensatory hypertrophy by recapitulating the neonatal pattern. In that model we found that miR-21 is one of the highest differentially expressed miRNA (~8x). Thus, we hypothesized that miR-21 may contribute to the development of hypertrophy by inducing down-regulation of antagonizing genes. To experimentally test the effect of miR-21 on cardiac myocytes, we generated adenoviruses harboring primary miR-21 or, uniquely, anti-miR-21 sequences. These viruses were used to infect cultured myocytes. Interestingly, overexpression of miR-21 resulted in extensive, dose-dependent, branching (sprouting) of the cells. Computational predictions by ’TargetScanS’ identified Sprouty 1 and 2 as potential targets. Subsequently, we confirmed down-regulation of sprouty by over-expression of miR-21. Conversely, knocking down miR-21, using anti-miR-21, resulted in enhanced expression of sprouty during growth-induced conditions. Immunocytochemical staining shows that it is localized to sarcomeric structures and the nucleus. Sprouty is a known inhibitor of the Ras-MAPK signaling pathway and is, concordantly, downregulated in many forms of cancer. Notably, sprouty also negatively regulates ureteric and tracheal branching during morphogenesis. In heart, sprouty has been suggested to control myocyte size and vascularization during mechanical stress-induced ventricular remodeling. Thus, we propose that upregulation of miR-21 during cardiac hypertrophy, induces down-regulation of sprouty, which results in activation of the Ras-MAPK pathway. Moreover, down-regulation of sprouty is necessary for the increased myocyte branching observed during hypertrophy.
Abstract 2344: Cumulative Radiation Dose Estimate From Medical Testing in Grown-Up Patients With Congenital Heart Disease
Authors: Ait-Ali Lamia , Botto Nicoletta , Andreassi Maria Grazia , Festa Pierluigi , Picano Eugenio
Published: July 2021

Background: The “Biological effects of Ionizing Radiation” (BEIR VII,2005) underlines “the need of studies of infants who are exposed to diagnostic radiation”.

Aim: to assess the individual cumulative lifetime radiological dose in grown up congenital heart disease (GUCH) patients.

Methods: In 41 consecutive operated GUCH patient (24 males, age= 27 ± 9 years old), followed in our outpatient clinic, a cumulative radiological history was collected with a structured questionnaire and access to lifetime hospital records. All patient underwent at least one surgical intervention during the infancy for Tetralogy of Fallot (n=18), aortic coarctation (n=10), anatomical/functional univentricular heart (n=8), other congenital heart disease (n=5) The cumulative exposure was expressed in milliSievert (mSv) and derived from average effective dose estimates of individual examinations proposed by the European Commission Medical Imaging Guidelines (2001). The attributable cancer risk was estimated from BEIR VII, 2005 document.

Results: On average, cumulative dose estimate was 22.3 ± 12.4 (mean ± SD) mSv per patient, equivalent to about 1115 ± 620 chest x-rays. Diagnostic and interventional catheterization accounted for the most important sources of exposure (see figure

). The median cumulative dose gave an average extra-risk of cancer of about 1 out of 200 patients (range, 1 in 448 to 1 out of 58).

Conclusion: the average contemporary GUCH patient is exposed to a significant cumulative radiological effective dose. Every effort should be done to justify the indications and to optimise dose delivery during ionizing testing.
Abstract 2357: Effect of Prolonged Thienopyridine Use on Long-term Clinical Outcomes After Drug-eluting Stents: Landmark Analysis from the TAXUS Trials
Authors: Stone Gregg W , Ellis Stephen G , Kong David K , Koglin Joerg , Friedman Mark I , Baim Donald S
Published: July 2021

Background
A recent non-blinded, observational landmark study from uncontrolled registry data by Eisenstein et al. suggested that thienopyridine (T) use beyond 1 year may reduce death and MI in patients who have received drug-eluting stents (DES). We performed a similar examination of slow-release paclitaxel-eluting stents (PES) in the prospective, randomized, double-blind TAXUS DES trials.

Methods
Using data from the TAXUS II-SR, IV and V trials, a landmark analysis was performed on the 2,523 patients who were free of death, MI and stent thrombosis (ST) through 1 year. Patients were divided according to stent type (PES vs bare metal stent [BMS]) and thienopyridine usage at a 1-year landmark point: PES T+ (N=578), PES T− (N=683), BMS T+ (N=574), and BMS T− (N=688). Subsequent events (ST, death, MI) were tabulated for the next 3 years in TAXUS II-SR and IV, and for 1 year in TAXUS V.

Results
Thienopyridine and aspirin usage were well matched between BMS and PES patients at all time-points. T+ patients at 12 months had no ST events through 4 years, while T− patients had 6 ST events (0.57%; p=0.045, log-rank). This difference was not significant for BMS T+/T− (0.0% versus 0.22%, p=0.49), and borderline significant for PES T+/T− (0.0% versus 0.92%, p=0.056). There was no corresponding difference in death at either 2 or 4 years, but there was a borderline reduction in MI at 2 years for PES T+/T− (0.35% versus 1.49%, p=0.08; interaction term p=0.09 between stent type and thienopyridine use), which disappeared at 4 years (2.79% versus 3.42%, p=0.565; interaction term p=0.35).

Conclusions
Thienopyridine use at 1 year was associated with fewer subsequent late ST events overall, which was more pronounced for PES than BMS. While there was a borderline reduction in MI at 2 years, no sustained impact on death or MI at 4 years was demonstrated. These data will be updated with one additional year of follow-up in all 2,523 patients at the time of presentation.
Abstract 2363: Effect Of Aspirin And Clopidogrel Resistance On Myonecrosis Following Percutaneous Coronary Intervention
Authors: Saw Jacqueline , Jokhi Percy , Starovoytov Andrew , Fox Rebecca , Wong Graham , Ramanathan Krishnan , Fung Anthony
Published: July 2021

Background:
The presence of aspirin and clopidogrel resistance is increasingly recognized. We seek to evaluate if patients with aspirin and/or clopidogrel resistance are predisposed to myonecrosis following percutaneous coronary interventions (PCI).

Methods:
This study is performed as a substudy of the Brief-PCI, which randomized 620 patients to 18hr or 2hr infusion of eptifibatide following PCI. To be eligible for our substudy, patients have to be pretreated with aspirin (≥5 days) and clopidogrel (either 75mg/d ≥5 days, or 300mg loading ≥6 hr), and have not received a glycoprotein IIb/IIIa inhibitor within the past 48hrs. Bedside point-of-care platelet aggregometry using Accumetrics VerifyNow™ Aspirin and Clopidogrel assays were performed at baseline prior to PCI. Patients with aspirin reaction unit (ARU) ≥550 were labeled as “aspirin resistant”. Patients with percent inhibition ≤20% on the VerifyNow™ Clopidogrel assays were labeled as “clopidogrel resistant”. Our primary endpoint is the prevalence of myonecrosis within 24hrs post-PCI (defined as elevation of Troponin I >1μg/L when baseline levels are negative, or peak CK-MB >3 times upper limit of normal and >50% higher than baseline value).

Results:
We enrolled 203 patients, of which 181 had aspirin resistance assessed, 188 had clopidogrel resistance assessed, and 169 had both assessed. There were 5% ± 1.6% who were aspirin resistant, 29% ± 3.3% who were clopidogrel resistant, and 1% ± 0.8% who were resistant to both. The overall prevalence of myonecrosis within 24hrs of PCI was 9% ± 2%. Patients who were resistant to both aspirin and clopidogrel had a higher prevalence of myonecrosis compared to those who had normal response (50% vs. 8%, p=0.031). There was no difference in myonecrosis prevalence among aspirin resistant patients compared to those with normal aspirin response (11% vs. 8%, p=0.754), or among clopidogrel resistant patients compared to those with normal clopidogrel response (11% vs. 7%, p=0.390). The mean ARU and percent inhibition was not different between those with or without myonecrosis.

Conclusion:
Our data suggests that only a small proportion of patients were resistant to both aspirin and clopidogrel, and these patients may have a higher prevalence of myonecrosis following PCI.
Abstract 2365: Pharmacogenomic Application Of The Haptoglobin Genotype To Identify Individuals With Diabetes Mellitus Who Benefit From Vitamin E Supplementation: A Prospective Randomized, Double-blind, Placebo Controlled Trial
Authors: Milman Uzi , Blum Shany , Shapira Chen , Aronson Doron , Miller-Lotan Rachel , Anbinder Yefim , Alshiek Junia , Bennett Lawrence , Kostenko Maria , Landau Michele , Keidar Shlomo , Levy Yishai , Khemlin Alexander , Radan Arman , Levy Andrew P
Published: July 2021

Background.
Large clinical trials of antioxidant therapy with vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major anti-oxidant protein, is a determinant of cardiovascular events in patients with diabetes mellitus (DM). The Hp gene is polymorphic with two common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior anti-oxidant protection as compared to the Hp 1 allelic product. In a retrospective analysis of HOPE participants with DM and the Hp 2–2 genotype, vitamin E significantly reduced the incidence of myocardial infarction and cardiovascular death. We sought to validate this observation in a prospective trial.

Methods and Results.
984 DM individuals with the Hp 2–2 genotype were randomized and treated with either natural source vitamin E (400IU/day) or placebo. The primary composite outcome was non-fatal myocardial infarction, stroke and cardiovascular death. The study was intended to last 4 years with initial evaluation of endpoints scheduled 12 months after enrollment of the first patient. At the initial evaluation, the primary composite outcome was significantly reduced in patients receiving vitamin E compared to placebo (1.0% vs. 3.8%, p=0.004). This was predominately due to a significant decrease in the incidence of non-fatal myocardial infarction (0.2% vs. 2.1%, p=0.004) and led to early termination of the study.

Conclusions
. Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2–2 genotype. (ClinicalTrials.gov number
NCT00220831
).
Abstract 2367: Omega 3 Fatty Acid Supplementation Reduce One-Year Risk of Atrial Fibrillation in Patients Hospitalized with Myocardial Infarction
Authors: Macchia Alejandro , Monte Simona , Pellegrini Fabio , Romero Marilena , Ferrante Daniel , Doval Hernan , Maggioni Aldo P , Tognoni Gianni
Published: July 2021

Background: Current medical strategies for avoidance of atrial fibrillation (AF) are of limited value. Anti-arrhythmic agents faced major challenges related to their limited efficacy and their serious and frequent side effects. Epidemiological studies, clinical trials and basic science support the role of Omega-3 fatty acids (n-3 PUFA) in reducing all cause mortality among patients with previous myocardial infarction (MI), mostly by reducing ventricular arrhythmias. However their effects regarding supraventricular arrhythmia are not well characterized.

Aim: To assess the effect of supplementation with n-3 PUFA for the prevention of AF.

Methods: Population study, linking administrative datasets from hospital discharge, prescription databases and vital statistics, including all consecutive patients with MI (code ICD-9: 410) in 6 Italian regions during a 3-year period. Follow up was extended up to one year or to time to event. A Cox regression model adjusted for propensity score (PS) quintiles was used. Further a PS-based 5 to 1 greedy matching algorithm and sensitivity analysis were used to assess robustness of our findings.

Results: Three thousand two hundred and forty-two (3,242) patients were identified and included in the analysis. Of these, 208 (6.4%) were exposed to n-3 PUFA during follow up. Four out of 208 (1.9%) patients exposed to n-3 PUFA were hospitalized with AF during follow up as compared with 467 out of 3,034 (15.4%) of those not exposed to supplement n-3 PUFA. The PS-quintiles adjusted hazard ratio (HR) estimate was 0.19 (95%CI 0.07– 0.51; p=0.001). The PS based 5 to 1 greedy matching algorithm and sensitivity analysis confirm main results (HR=0.13; 95%CI 0.04 – 0.44; p=0.001).

Conclusion: n-3 PUFA reduce the occurrence of one year AF in patients hospitalized with MI.
Abstract 348: Effects of Normalizing Hyperlipidemia on Oxidative Stress and Disease Progression in a Mouse Model of Aortic Valve Stenosis
Authors: Miller Jordan D , Berry Christopher J , Serrano Kristine M , Weiss Robert M , Iyengar Nikhil K , Zimmerman Kathy A , Young Stephen J , Heistad Donald D
Published: July 2021

Treatment of hyperlipidemia produces functional and structural improvement in atherosclerotic vessels. Effects of treatment of hyperlipidemia on structure and function of the aortic valve, however, are controversial, and may be confounded by pleiotropic effects of drugs. We hypothesized treatment of hyperlipidemia using a “genetic switch” in Reversa mice (
Ldlr
−/ −
/
Apob
100/100
/
Mttp
fl/fl
/Mx1
Cre

+

/
+
) would reduce oxidative stress and slow the progression of aortic valve disease. Following 6 months of hyperlipidemia (cholate-free Western diet = WD = 0.25% chol., 21% fat; total cholesterol levels >700 mg/dl), superoxide levels were significantly elevated in the aortic valve (dihydroethidium fluorescence: control = 5 ± 2 U/pixel, WD = 13 ± 3 U/pixel; p < 0.05) with very small reductions in maximum leaflet separation distance obtained from echocardiograms (control = 0.94 ± 0.07 mm, WD =0.89 ± 0.02 mm; p<0.05). In mice maintained on WD for an additional 6 months, leaflet separation decreased to 0.66 ± 0.06 mm (p < 0.05). Rapid normalization of cholesterol levels at 6 months (NC; total cholesterol <200 mg/dl) using a “genetic switch” normalized superoxide levels in the valve (NC = 4 ± 2 U/pixel, p = n.s. versus control animals) and prevented further reductions in leaflet separation distance (NC = 0.89 ± 0.05 mm; p = n.s.). Computerized planimetry of aortic valve area from high resolution cross-sectional magnetic resonance images through the aortic root (4.7 Tesla magnet, 0.04 mm
2
in-plane pixel resolution) confirmed that normalization of cholesterol levels significantly slowed the rate of progression of valve stenosis (Δ valve area from 6–12 months: HC=−6.4 ± 4 %/month, NC = 0.6 ± 4%/month, p<0.05). Collectively, these data suggest that normalization of lipid levels in hypercholesterolemic mice with mild aortic valve disease normalizes oxidative stress and slows the progression of aortic valve stenosis.
Abstract 2422: Depression and Anxiety in Adult Patients with Congenital Heart Disease
Authors: Ohta Mayumi , Kurosawa Yuri , Nakanishi Toshio
Published: July 2021

Background:
Advances in the management of congenital heart disease (CHD) have resulted in increased survival of patients (pts) into adulthood, but those pts may encounter new medical and social problems in adulthood. Further, even if their medical condition may be good, social adaptation may be insufficient because of the psychiatric and/or psychological problems. However, little is known about psychosocial functioning of adults with CHD. The aim of this study was to evaluate psychopathological problems in adult pts with CHD.

Methods:
We evaluated psychopathological adjustment in 60 consecutive adult pts (20 –52 yrs of age) with CHD, who were hospitalized at our institute, including tetralogy of Fallot (9 pts), transposition of the great arteries (8 pts), single ventricle (7 pts), tricuspid atresia (5 pts), ventricular septal defect (3 pts), and miscellaneous (28 pts). Severity of cardiac conditions, psychiatric/ psychological symptoms, education, and career were assessed, and psychiatric analysis was performed in each patient. We used a standardized semi-structured psychiatric interview with the self-administered scale Minnesota Multiphasic Personality Inventory (MMPI).

Results:
17% (10 pts) had clinical symptoms of depression and anxiety, and these pts met the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) for depression and anxiety, based on the diagnostic interview and MMPI. In addition, 23% (14 pts) showed abnormality in several scales, such as hypochondriasis, depression, and hysteria in MMPI, although they did not meet the criteria of psychopathology. In these pts, emotional problems were expressed as physical and general malaise in MMPI data. A statistically significant correlation was observed between the MMPI data and medical severity. The MMPI data did not correlate with the social background, such as education and work experience.

Conclusions:
The frequency of depression and anxiety is high in adults with CHD, especially in severe CHD, irrespective of education and career. Even if there may be no psychological symptoms and pts appear to be well adapted, there is a potential risk of depression and anxiety in adults with CHD. Optimal psychiatric interventions remain to be clarified.
Abstract 2437: Atrial Fibrillation Ablation in Patients with Therapeutic INRs: Comparison of Strategies of Anticoagulation Management in the Periprocedure Period
Authors: Wazni Oussama M , Beheiry Salwa Salwa , Hao Steven , Hongo Richard , Kanj Mohammad , Schweikert Robert , Arruda Mauricio , Martin David O , Saliba Walid , Natale Andrea
Published: July 2021

Introduction
: Management of anticoagulation peri-pulmonary vein isolation (PVI) to cure atrial fibrillation is necessary to prevent thromboembolism while avoiding complications from anticoagulation. The best approach to management of anticoagulation around the AF ablation is not known.

Methods:
We compared outcomes in consecutive patients undergoing PVI for chronic AF. Initially coumadin was stopped 3 days before ablation and a TEE was performed to rule out clot. Enoxaparin, initially 1mg/kg twice daily (Group1) and then 0.5mg/kg twice daily (Group 2) was used to bridge patients after ablation. Subsequently,Group 3 patients were kept on warfarin keeping the INR between 2–3. Heparin bolus (100 –150 units/kg) was given before trans-septal punctures. The infusion rate was adjusted to keep the activated clotting time in the range of 350 to 450 seconds. Minor bleeding was defined as hematoma not requiring intervention. Major bleeding was defined as either cardiac tamponade, hematoma requiring intervention or bleeding requiring blood transfusion.

Results
(Table

): PVI was performed in 355 patients (Group 1±105, Group 2±100, Group 3±150. More patients had spontaneous echo contrast in groups 1 and 2. In group 1 one patient had an ischemic stroke vs. 2 patients in group 2 and no patients in group 3. In group 1 there were 13 patients with minor bleeding and 9 patients with major bleeding. In group 2 19 patients had minor bleeding and 2 patients developed pericardial effusion with no tamponade. In group 3 eight patients developed minor hematoma and no major bleeding.

Conclusion
: This present study shows that continuation of warfarin through PVAI without the need for administration of enoxaparin pre and post PVI is safe and efficacious. Utilization of this strategy can prevent suboptimal anticoagulation that may increase the risk for stroke and eliminates the need for enoxaparin that is associated with more bleeding and is costly and inconvenient.

Patient Characteristics and Results
Abstract 2439: Visually-Guided Pulmonary Vein Isolation Using a Balloon Ablation Catheter to Treat Patients with Paroxysmal Atrial Fibrillation: One-Year Clincial Outcome Following a Single Ablation Procedure
Authors: Reddy Vivek Y , Neuzil Petr , Themistoclakis Sakis , Bonso Aldo , Rossillo Antonio , Raviele Antonio , Saliba Walid , Schwiekert Robert , Ernst Sabine , Kuck Karl-Heinz , Ruskin Jeremy N , Natale Andrea
Published: July 2021

Introduction:
During AF catheter ablation, placing contiguous point ablation lesions to electrically isolate the PVs can be technically challenging. A novel balloon catheter (EAS, Endoscopic Ablation System, Cardiofocus, Inc.) which utilizes an endoscope for real-time visualization of the LA-PV junction and adjustable arcs of ablative light energy was used to isolate the PVs. This report details the one-year follow-up results after a single treatment.

Methods:
In this three-center study, 30 patients with a history of symptomatic drug-resistant paroxysmal AF were studied: Sex: M/F = 26/4 (87%/13%); Age 53 ± 11 years (28 –73); AF duration: 6.0±4.9 years (range 0.4 –24.1); LA diameter: 4.3±0.5 cm (range 3.1– 4.9); LVEF 67.6±8.9% (range 45– 86). PV isolation using the EAS was confirmed using a circular mapping catheter. There were no exclusion criteria related to PV shape/number.

Results:
Electrical PV isolation was achieved in 91% (105/116) of the targeted PVs. An average of 14 energy deliveries/PV were delivered (range 2– 40). There was no significant PV stenosis. There were three primary adverse events. Following a 90-day blanking period, 70% (21/30) of patients were free from symptomatic AF episodes >1 min at 6-month follow-up, and 67% (20/30) were free from symptomatic AF episodes lasting >1 minute through one-year follow-up. Two treatment success were on AADs for indications other than AF. An examination of the treatment failures was conducted. There were no differences between chronic treatment successes and failures in sex (p=0.56), age (p=0.22), EF (p=1.0), LA diameter (p=0.70), years of AF (p=0.30) and acute PV isolation of all PVs versus less than all PVs (p=0.66). Most treatment ``failures” did not require repeat AF ablation due to minimal symptoms. One underwent subsequent RF ablation for AF in follow-up; PV reconnections were noted.

Conclusions:
A single treament with the visually-guided EAS ablation system appears feasible, safe and efficacious to treat patients with paroxysmal AF.
Abstract 2449: Clinical Outcomes in Women with Stable Coronary Artery Disease Randomized to Optimal Medical Therapy With or Without PCI: Pre-Specified Subset Analysis of the COURAGE Trial
Authors: Boden William E , Jacobs Alice K , Teo Koon K , Hartigan Pamela M , Maron David J , Kostuk William J , Chaitman Bernard R , Mancini John , Dada Marcin , Bates Eric , Booth David C , Weintraub William S , O’Rourke Robert A
Published: July 2021

Background:
The main results of the COURAGE Trial showed no significant differences in the primary outcome of all-cause mortality or non-fatal MI, or in major secondary outcomes (the composites of death, MI or stroke, and hospitalization for ACS) in the 2,287 patients with stable coronary artery disease randomized to optimal medical therapy (OMT) with or without percutaneous coronary intervention (PCI). In a pre-specified subset analysis, women who received an initial strategy of PCI during a median 4.6 year follow-up appeared to benefit for death or MI, but the interaction P value for this comparison (0.03) exceeded the nominal pre-specified value for all trial subgroup interactions (P<0.01) .

Methods:
We explored various pre-specified clinical endpoints in the 338 women (15%) of the COURAGE cohort who were randomized to PCI + OMT vs. OMT alone. Chi-Square analyses were conducted for the following outcomes between groups (time to first event): death or MI; death; MI; the composite of death, MI or stroke; death, MI or hospitalization (Hosp) for ACS; and Hosp for CHF.

Results:
There were no significant differences between treatment arms for major pre-specified cardiovascular events in men, but there was apparent benefit for many clinical outcomes in women randomized to PCI + OMT vs. OMT alone, although in all but one comparison (i.e., CHF), the P values exceeded the pre-specified value for interaction (P < 0.01) during long-term follow-up (Table

):

Conclusions:
Although the primary endpoint and death alone were not significantly different between groups, women randomized to PCI appeared to fare better than those randomized to OMT alone for selected clinical outcomes. However, because women comprised only 15% of the COURAGE population, it is unclear whether these findings indicative true clinical benefit for PCI in women, or alternatively may represent a statistical play of chance or type II error. These important findings may warrant additional investigation and analysis.
Abstract 2456: High HDL-cholesterol Levels Are Paradoxically Associated With
Increased
Atherosclerosis And
Increased
Coronary Heart Disease (CHD) Events In Metabolic Syndrome Subjects: The Multi-ethnic Study Of Atherosclerosis (MESA)
Authors: Watson Karol E , Srikanthan Preethi , Schreiner Pamela J , Post Wendy , Burke Gregory L , Casillas Adrian , Barr R. Graham , O’Leary Daniel H , Fogelman Alan M
Published: July 2021

Background
: In population studies high HDL is associated with fewer CHD events, however in certain people high HDL does not appear to protect and recent work suggests that HDL can become dysfunctional in settings of inflammation. Since Metabolic Syndrome (MetSyn) patients often have systemic inflammation, we hypothesized that high HDL might
not
be protective in this group.

Methods
: We analyzed data from 6,814 subjects in MESA; 2,362 of whom had MetSyn. Subjects were stratified by HDL into low (< 40), mid (40 –59) and high (≥ 60 mg/dL) groups. Outcomes were cIMT, coronary calcium (CAC), and CHD events over 3 years of follow up. Cox proportional hazards models assessed the association of HDL with CHD events.

Results
: In non-MetSyn subjects, outcomes were worst in the low HDL group and improved as HDL increased. In MetSyn subjects, however, an unexpected U-shaped relationship was seen. The most favorable results were in MetSyn subjects with mid HDL (40 –59), while worse outcomes were seen with either low (< 40) or high (≥ 60) HDL. cIMT was 1.23, 1.14 and 1.26 mm for low, mid and high HDL respectively (p mid vs. high = 0.04). Log
e
CAC was 4.63, 4.37 and 4.66 for low, mid and high HDL (p = 0.09). CHD rates were 3.7%, 1.8% and 4.1% for low, mid and high HDL (p = 0.027). In multivariate analysis, high (vs. mid) HDL remained associated with CHD events in MetSyn (HR 2.44 [1.03–5.82]).

Conclusion
: Although HDL is associated with decreased CHD in general populations, in certain people HDL doesn’t protect. In our data MetSyn subjects with HDL ≥ 60 had poorer outcomes than those with HDL 40 –59, which suggests that HDL-C is a complex marker that must be interpreted in light of a person’s metabolic profile and inflammatory status.
Abstract 2466: Transapical Aortic Valve Implantation At One Year
Authors: Walther Thomas , Falk Volkmar , Borger Michael A , Kempfert Jörg , Fassl Jens , Rückert Yvonne , Rastan Ardawan , Linke Axel , Schuler Gerhard , Mohr Friedrich W
Published: July 2021

Objective: To evaluate the results of minimally invasive transapical aortic valve implantation (TAP-AVI) at one year follow-up.

Methods: 61 high risk patients with symptomatic aortic valve stenosis received TAP-AVI at our institution since 02/2006. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Edwards SAPIEN™ THV, Edwards Lifesciences, Irvine, CA, USA) was used. All valves were implanted in a hybrid operative theatre under fluoroscopic and echocardiographic guidance. Patient age was 82.7 ±4.5 years, 79% were female, NYHA class was 3.4 ±0.5, previous cardiac surgery had been performed in eight patients, logistic EuroSCORE risk for mortality was 28.1 ±11.9% and STS score risk for mortality was 15.9 ±8.6%.

Results: TAP-AVI was performed successfully in 58 (95.1%) of the patients; three patients required early conversion due to proximal dislocation, secondary dissection of the aortic root and main stem occlusion. Two of the converted patients were discharged alive. A total of 73.7% of the patients were treated completely off-pump, secondary use of cardiopulmonary bypass was required in 3/39 (7.8%). 82% of the patients were extubated early after 80 ±17min. Echocardiography revealed good valve function; trivial to mild (1°), paravalvular incompetence was present in 41%. At thirty days four (6.6%) patients and during follow-up eight patients (15.3%) died, all with good valve function at most recent echo. Thirty day survival was 93 ±3.4%, six months survival 74.4 ±6.6% and one year survival 70.5 ±7.3%, respectively. There were no neurological events.

Conclusions: Transapical aortic valve implantation is a safe, minimally invasive and off-pump technique to treat high risk patients with aortic stenosis. One year results are good, especially when considering the overall risk profile of these patients.
Abstract 2486: Early Diastolic Mitral Annulus Lengthening Velocity Reflects Coupling between Systolic and Diastolic Function
Authors: Opdahl Anders , Remme Espen W , Helle-Valle Thomas , Vartdal Trond , Pettersen Eirik , Elstad Maja , Edvardsen Thor , Walloe Lars , Smiseth Otto A
Published: July 2021

Background:
Peak early-diastolic mitral annulus velocity (E’) by tissue Doppler imaging (TDI) has been introduced as a marker of diastolic function. This study investigates mechanisms of E’.

Methods:
In 7 anesthetized dogs we measured E’ and systolic long-axis shortening (SS) by sonomicrometry and TDI, and the time constant (
tau
) of LV relaxation by micromanometer. In 8 healthy subjects (HS) we measured E’ by TDI and SS by M-mode echo at baseline and during lower body negative pressure (LBNP). We studied 6 patients with myocardial infarction, acutely and after 6 –12 months.

Results:
In dogs there was a strong correlation between E’ and SS (Fig 1

), suggesting that E’ is determined primarily by systolic function. However, during ischemia which increased
tau (p<0.01)
, the relationship between E’ and LV end-diastolic pressure (LVEDP), shifted markedly downwards (Fig 2

). During volume loading which increased LVEDP (p<0.01), the relationship between E’ and
tau
shifted markedly upwards (Fig 3

). Consistent with findings in dogs, healthy subjects demonstrated a strong correlation between E’ and SS during LBNP (Fig 4

). However, in patients with chronic myocardial infarction the relationship between E’ and systolic shortening was shifted downwards (Fig 4

).

Conclusions:
During a wide range of hemodynamic conditions there were strong correlations between E’ and SS. The shifts in the relationships between E’ and LVEDP during ischemia and between E’ and
tau
during volume loading, indicates that diastolic function modulates E’. These observations indicate a tight coupling between systolic and diastolic function, and challenge the concept that E’ is a specific marker of LV relaxation.

Fig 1

Experimental study

Fig 2 Experimental study

Fig 3 Experimental study

Fig 4 Clinical study