bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2379: No Association of
PLIN
Polymorphisms with Hemorrhagic and Ischemic Strokes
Authors: Song Weihua , Chen Jingzhou , Sun kai , Yu Hui , Hui Rutai
Published: July 2021

Background and Purpose

Perilipin is a family of proteins that coat the intracellular lipid droplets and expressed in adipocytes, steroid-producing cells and atherosclerotic lesions. I t has been linked to the formation of foam cells and rupture of atherosclerotic plaques. To our knowledge, no other studies have investigated the association between polymorphic variation in
PLIN
and stroke. We hypothesized that genetic variations in
PLIN
might contribute to the susceptibility to stroke. We tested the hypothesis in two case-control studies.

Methods

Six
PLIN
tag SNPs (rs7176403, rs8179078, rs6496589, rs8179043,
rs894160
, rs1052700,) were genotyped in 1571 stroke patients (690 cerebral thrombosis, 429 lacunar infarction, 452 intracerebral hemorrhage) and 1638 controls, by polymerase chain reaction (PCR) followed by ligase detection reaction (LDR) in combination with sequencing, and by PCR and restriction fragment length polymorphism. A SHEsis software was used to analyze pairwise linkage disequilibrium, and haplotype association. The results were confirmed in another independent case-control study, with 120 stroke patients and 240 controls.

Results

No association was found between the
PLIN
variants and stroke in the first study (P>0.05). Six common haplotypes were identified within the study population, none of which was associated with stroke and all its subtypes (P>0.05). The findings were confirmed in the second study (P>0.05).

Conclusions

The data represent an important negative finding and that the common variants studied here do not have a major influence on susceptibility to stroke, even if perilipin has been linked to the formation of foam cell and rupture of human atherosclerotic plaques.
Abstract 2393: Similar Long-Term Outcomes After PCI Success, PCI Failure, and no PCI in the Occluded Artery Trial (OAT)
Authors: Buller Christopher E , Dzavik Vladimir , Forman Sandra A , Ruzyllo Witold , Buszman Pawel E , Michalis Lampros K , Mancini G. B. John , Renkin Jean , Pfisterer Matthias E , Thomas Boban , Lamas Gervasio A , Hochman Judith S
Published: July 2021

Background:
The Occluded Artery Trial (OAT) showed that a strategy of routine percutaneous coronary interventions (PCI) for occluded infarct-related coronary arteries identified up to 28 days post-MI does not reduce the primary end point of death, MI or class IV CHF compared to medical therapy alone (MED). However, PCI was not universally attempted in patients assigned PCI, and was not always successful when attempted. Moreover, some MED patients underwent early PCI. Using an as-treated analysis, we compared the outcomes of (1) successfully-treated PCI patients to medically-treated MED patients, and (2) PCI-assigned patients according to PCI success versus failure.

Methods:
Of 2201 patients randomized in OAT (2166 + 35 substudy), 1101 were assigned PCI and 1100 to MED. PCI assignment was categorized as attempted and successful (Success), attempted and unsuccessful (Fail), or No Attempt. MED assignment was categorized as medical only (Med Only) or crossover (X-Over) if PCI of the occlusion was performed in ≤30 days. Life table estimates of primary and secondary outcomes were calculated to compare as-treated categories.

Results:
Baseline characteristics of PCI Success and MED Only groups were similar. Compared to PCI Success, PCI Fail patients were more likely to be male, with higher rates of prior PCI, Killip Class 2– 4, and higher LV end-systolic sphericity index. No significant differences in primary or secondary outcomes were observed between PCI Success versus MED Only, or between PCI Success and PCI Fail. Med X-Over and PCI No Attempt groups were small.

Conclusions:
As-treated analysis does not reveal important differences in outcome, whether the comparison is between those with PCI success versus medical therapy alone, or between PCI success and PCI failure. These data indicate that the primary intention-to-treat results of OAT would not be altered by higher PCI success rates.

60-Month Life Table Event Rate Estimates
Abstract 2406: Comparison Of Invasive Procedures And Medical Treatment In Patients With ST-segment Elevation Myocardial Infarction: Impact Of Initial Admission To Hospitals With Versus Without Catheterization Laboratory. Results From The German ACOS Registry.
Authors: Skarlos Alexandros , Gitt Anselm K , Juenger Claus , Wienbergen Harm , Zahn Ralf , Senges Jochen , Zeymer Uwe
Published: July 2021

Introduction: The aim of this analysis was to evaluate the rate of invasive and revascularization procedures and adherence to guideline recommended therapies in patients with STEMI initially admitted to hospitals with and without catheterization laboratory in clinical practice.

Methods: Between 07/2000 and 12/2002 16817 patients with an acute coronary syndrome from 154 hospitals have been included in the ACOS registry. 8303 of these patients presented with ST-segment elevation myocardial infarction. 6351 patients (76,5%) were initially admitted to a hospital with catheterization laboratory, 1952 (23,5%) in a hospital without catheterization laboratory.

Results: We observed significant differences for treatment during the first 48h and revascularization procedures (table

). In the univariate analysis the total in-hospital and 1-year mortality was significantly lower in patients with initial admission to hospitals with catheterization laboratory (8.8% vs. 11.5%, p<0.001 and 13.7% vs. 19.9%, p<0.0001). However, this was statistically significant after adjustment for age, gender, history of myocardial infarction, diabetes, renal insufficiency, heart rate < 100/min and systolic blood pressure > 100 mmHg for 1-year-mortality only (Odds ratio 0.75; 95% CI 0.65 – 0.88) and not for in-hospital mortality (Odds ratio 0.91; 95% CI 0.76 – 1.10).

Conclusions: In clinical practice patients with STEMI admitted to hospitals with catheterization laboratory are treated with significantly higher rates of reperfusion and guideline recommended adjunctive therapies. This is associated with a lower 1-year mortality.
Abstract 354: ZnT-1 Expression in the Human Atria and New Insights on its Activity as an Inhibitor of L-type Calcium Channels
Authors: Etzion Yoram , Kolt Shiri , Beharier Ofer , Ganiel Amir , Liat Buzaglo , Shalev Aryeh , Novack Victor , Sahar Gideon , Katz Amos , Moran Arie
Published: July 2021

BACKGROUND
: Recent findings indicate that the membranous protein ZnT-1 acts as an inhibitor of L-type calcium channels (LTCC). However, no direct interaction between ZnT-1 and the LTCC α
1
C subunit was demonstrated. Recently, we found that atrial tachypacing in rats augments the expression of ZnT-1 in conjunction with AERP reduction. Therefore, we postulated that ZnT-1 may play a role in atrial tachycardia remodeling of patients with AF. In this study, we assessed the atrial expression of ZnT-1 in humans with AF or sinus rhythm (SR). In addition, in order to explore the mechanism of action of ZnT-1 we used heterologous expression system, and tested the possibility that ZnT-1 interacts with the β-subunit of the LTCC.

METHODS AND RESULTS
: From 39 patients (27 in SR and 12 in AF) undergoing open heart surgery, we collected right atrial appendage tissue. The expression of ZnT-1 was analyzed. β-actin served as an internal loading control and data was compared to a rat standard (STD). Overall, AF patients (n = 12) had median ZnT-1/β-actin of 1.80 STD (inter-quartile range 1.26 to 2.85) vs. 0.73 STD (0.24 to 1.64) in the SR group (p = 0.002). Multivariate analysis determined that AF and increased BMI are the only independent variables associated with higher levels of ZnT-1. In
Xenopus
oocytes, the absence of the β-subunit prevented the inhibition of LTCC activity by ZnT-1 (127 ± 43nA and 153 ± 39nA for control and ZnT-1 containing oocytes, respectively, p>0.5, n = 8). In addition, ZnT-1 failed to inhibit the current when the α-subunit was truncated in the part essential for the interaction with the β subunit (2037 ± 300nA and 1938 ± 341nA for control and ZnT-1 containing oocytes, respectively, p>0.5, n = 3). Direct interaction between ZnT-1 and the LTCC β-subunit was demonstrated by co-immunoprecipitation of ZnT-1-myc and the β-subunit, using anti-myc antibodies (n = 3)

CONCLUSIONS
: This work provides first evidence for an increased ZnT-1 expression in patients with AF and marks it as a putative missing link in the development of atrial electrical remodeling. An interaction of the LTCC β-subunit and the ZnT-1 plays a role in the molecular mechanism by which ZnT-1 inhibits the LTCC.
Abstract 2416: Gender Disparities In Treatment After Coronary Artery Bypass: A New Twist On An Old Problem
Authors: Doering Lynn V , Cross Rebecca L , Irwin Michael R , Magsarili Marise C , Cowan Marie J
Published: July 2021

Background: Treatment disparities that disadvantage women following coronary artery bypass graft (CABG) surgery have been reported. However, postoperative treatment of depression has not been assessed in this population. The purpose of this study was to evaluate treatment rates for depression and routine postoperative therapies in men and women after CABG.

Methods: Within the first month after post-CABG hospital discharge, 206 patients (age 66 ± 11 years, 99 [48%] men) from three cardiac surgery centers were evaluated for the presence of major depression using structured clinical interviews (Structured Clinical Interview for DSM [SCID] or Diagnostic Interview and Structured Hamilton [DISH]). Medical records were reviewed and patients were queried to identify postoperative use of antidepressants, aspirin, statins, beta blockers and angiotensin converting enzyme inhibitors. Gender comparisons were conducted by t-tests and chi-square. Odds ratios (OR) and confidence intervals (CI) for treatments by gender were generated by multivariate logistic regression.

Results: Rates of major depression were similar in men and women (19 [19%] vs. 18 [17%], p = .66), but men were less likely than women to receive antidepressants (3 [3%] vs. 12 [11%], p = .03). Even when antidepressant use was considered together with age, depression status, and other medications, the disparity favoring its use in women remained (OR = 5.87, CI = 1.2 – 29.1, p =.03). Women were less likely than men to receive statins (OR = 0.3, CI = 0.14 – 0.92, p =.03) and aspirin (OR = 0.3, CI = 0.14 – 0.67, p =.003).

Conclusion: For both men and women, major depression after CABG is undertreated. While women remain less likely than men to receive standard therapies for coronary artery disease after CABG, men are less likely than women to receive antidepressants. Because depression is associated with increased cardiac mortality and morbidity, these findings emphasize the importance of its identification and treatment in all CABG patients. Clinicians should guard against gender bias in assessing the need for antidepressant treatment, as well as in the application of more routine therapies.
Abstract 2430: Should All Octogenarians Who Meet Criteria Receive an Implantable Cardioverter Defibrillator?
Authors: Phatak Kavita , Makati Kevin , Holland Marian , Baig Sara , Kim Michael H , Link Mark , Passman Rod
Published: July 2021

Background:
There are no upper age restrictions for ICD implantation, though guidelines state that placement should be reserved for those with expected survival of > 1 year. In octogenarians, competing comorbidities may limit the mortality benefit of ICDs.

Methods:
A retrospective cohort study was used to identify octogenarians who received ICD implantation and follow-up at Northwestern Memorial Hospital or Tufts New England Medical Center between 1990 and 2006. The primary endpoint was death within 1 year of implant.

Results:
The study identified 241 octogenarians. Mean age 83.3 ± 3.1 years, 79% male, 87% coronary disease and 35% implanted for primary prophylaxis. Mean EF 31 ± 13%, creatinine 1.49 ± 0.71 mg/dl, and mean survival was 3.9 ± 0.3 years. Death within 1 year of implant occurred in 32 (13.2%) patients. Univariate predictors of 1-year mortality included EF ≤ 20% and creatinine ≥ 1.5 mg/dl (p < 0.01 and 0.04, respectively). Cox proportional analysis demonstrated that EF ≤ 20% was the only independent predictor of death within 1 year of ICD implant [Hazard Ratio = 3.2 (95% CI 1.5– 6.5; p<0.002)] and was associated with a 48% 1-year mortality. Of these patients, 6 (19%) received appropriate ICD therapy prior to death; the mean time from therapy to death was 3 months.

Conclusion:
Octogenarians with EF ≤ 20% have a very high 1-year mortality despite ICD implantation. A minority of these patients will receive appropriate ICD therapy during this time. These results would be expected to have significant impact on the cost-effectiveness of ICDs and should be considered when evaluating device implantation in this population.
Abstract 2431: Left Ventricular Scar Burden Predicts Life-Threatening Arrhythmia in Recipients of Implantable Cardioverter Defibrillilators
Authors: Netrebko Pavlo I , Geyfman Vitaly , Nassef Louis A , Storm Randle H , Oren Jess W , Cotarlan Vlad , Vijayaraman Pugazhendi , Shirani Jamshid
Published: July 2021

Objective.
Implantable cardioverter defibrillators (ICD) reduce arrhythmic deaths and are implanted based on LV ejection fraction (LVEF) and symptoms. Myocardial scar is a substrate for ventricular tachyarrhythmia (VT). We aimed to assess if number of LV scar segments [#SS, by cardiac magnetic resonance (CMR)] would predict life-threatening VT in recipient of ICD.

Methods.
Among 722 recipients of ICD (2002–2006), 54 [age 32– 84 (mean 63±12) years, 89% men, 76% ischemic, LVEF ≤35%] had CMR with delayed gadolinium enhancement prior to ICD. Using a 17-segment LV model, presence of scar was determined. End point was defined as confirmed VT requiring termination by anti-tachycardia pacing or shock.

Results.
At a mean follow-up of 15 (median 11.5) months, 12 (22%) patients reached end point. Univariate analysis identified LVEF and #SS as predictors whereas age, coronary artery disease, diabetes, hypertension, medications (anti-arrhythmic, beta-blocker, angiotensin-converting enzyme inhibitor, statin), creatinine, LV end-diastolic volume or LV mass were not predictive. #SS was higher in those who reached endpoint (8.5±1.2 vs 5.2±0.7, p=0.03). By receiver operator curve, a cut-off of ≥7 scarred segments identified those at high risk for VT (Graph - open circles are those with <7 scarred segments). By logistic regression, after control for EF, #SS remained significant (P 0.03) with 1.3 times higher incidence of VT per added scarred segment. LVEF and #SS did not correlate (p=0.07).

Conclusion.
Presence of large scar burden predicts VT in patients with advanced LV dysfunction. Assessment of myocardial scar burden by CMR may improve risk stratification prior to ICD implantation.
Abstract 2438: Local Bipolar Atrial Electrogram Monitoring during the Extensive Encircling Pulmonary Vein Isolation: Implications of the ``QS Pattern” in the Local Bipolar Atrial Electrogram after the Ablation
Authors: Otomo Kiyoshi , Taniguchi Hiroshi , Nagata Yasutoshi , Uno Kikuya , Iesaka Yoshito
Published: July 2021

BACKGROUND During the extensive encircling pulmonary vein (PV) isolation (EEPVI) for atrial fibrillation (AF), it is crucial to recognize whether or not a sufficient lesion was created by an ablation in each ablation site. The local electrogram (EG)-based criteria to predict a sufficient local lesion formation, however, remain to be established. This study was performed to define local EG-based criteria for the local lesion formation during the EEPVI for AF.

METHODS Among 31 patients (pts) with AF who had successful EEPVI during coronary sinus pacing, bipolar local EGs at 2271 ablation sites (73+/-19 sites/pt, posterior wall (PW) of the left atrium (LA)/anterior LA-PV junction=976/1295 sites) before and after energy delivery were reviewed. In EEPVI, ipsilateral PVs, antral regions and parts of the PW of the LA were isolated as a whole by linear ablation at the PW of the LA and semi-linear ablation at the anterior LA-PV junction. Each energy application was performed with a temperature controlled mode (maximal temperature: 55 degrees Celsius, maximal output: 35 watt) and duration of 25 to 35 seconds.

RESULTS After the ablation, all PVs, antral regions and parts of the PW of the LA were successfully isolated in all 31 pts (duration of each energy application: 31+/-3 sec/site, total energy application time: 37+/-10 min/pt). After the effective ablation at each site, the local EGs exhibited predominant reduction in the amplitude of positive deflection (Ap) as compared to that of negative deflection (An) (% reduction in Ap vs An: 91+/-10 vs 30+/-59%; p<0.01, Ap/An ratio before vs after ablation: 2.3+/-3.4 vs 0.3+/-0.1; p<0.01) as well as total amplitude reduction (67+/-22%) and EG widening (57+/-43%), and the morphology of the local EG changed to the ``QS” or ``rS” patterns. At 25 sites without those morphological changes, residual LA-PV conduction gaps were observed and additional ablations were required to achieve a complete EEPVI in 20 pts.

CONCLUSION We propose that a morphological change of local EGs to ``QS” or ``rS” patterns with predominant attenuation of positive deflection of local EGs can reflect sufficient local lesion formation and can be one of the practical endpoints for energy delivery at each ablation site during the EEPVI.
Abstract 2463: Impact of Donor to Recipient Weight Ratio on Survival after Heart Transplantation: Analysis of the United Network for Organ Sharing Database
Authors: Patel Nishant D , Weiss Eric S , Nwakanma Lois U , Russell Stuart D , Baumgartner William A , Shah Ashish S , Conte John V
Published: July 2021

Introduction
: Accepted donor criteria for heart transplantation limit allografts to donors within 20–30% of the recipient’s weight. We analyzed the impact of donor to recipient (DR) weight ratio on survival after heart transplantation.

Methods
: Adult heart transplant recipients reported to the United Network for Organ Sharing from 1999–2007 were divided into 3 groups based on DR weight ratio: <0.8, 0.8–1.2, and >1.2. Kaplan-Meier methodology was used to estimate survival. Propensity-adjusted Cox regression modeling was used to analyze predictors of mortality.

Results
: 15284 heart transplant recipients were analyzed: 2078 had weight ratio of <0.8, 9684 had 0.8–1.2, and 3522 had >1.2. Survival was not statistically different between groups (Figure

). Among patients with weight ratio <0.8, survival was lower for recipients with high pulmonary vascular resistance (PVR) (>4 Woods units) (Figure

). Among recipients with high PVR, 5-year survival was similar for those with weight ratio 0.8–1.2 and >1.2
(p
=0.44
).
Propensity-adjusted multivariable analysis demonstrated that weight ratio <0.8 did not predict mortality (HR 1.09; 95% CI 0.94–1.27;
p
=0.21). Five-year survival after propensity matching was not statistically different between those with weight ratio <0.8 versus ≥0.8 (
p
=0.37).

Conclusions
: Weight ratio did not predict mortality after heart transplantation. Undersized allografts in recipients with normal/low PVR did not adversely effect survival. Oversized allografts in recipients with high PVR did not provide survival advantage over normal-sized allografts. Extending donor criteria to include undersized hearts in select recipients should be considered.
Abstract 2474: Dynamic Change in LV Twist Mechanics in a Canine Model of Pacing-Induced Heart Failure
Authors: Wang Jianwen , Nagueh Sherif F , Mathuria Nilesh , Gilbert April L , Schulz Daryl G , Panescu Dorin , Shih Hue-Teh , Khoury Dirar S
Published: July 2021

Background
: LV twist may reflect LV contractility under different conditions. This study investigated LV twist dynamics and its determinants in a canine model of congestive heart failure (CHF).

Methods
: Pacemakers and percutaneous leads were implanted in 8 adult hound dogs (mean weight, 38 kg), and continuous chronic RV pacing was applied at 230–250 bpm until CHF induction. Subsequently, pacing was turned off to allow the heart to recover. Echocardiography and LV catheterization were performed simultaneously at baseline, during CHF while pacing was temporarily switched off, and during recovery from CHF after pacing was stopped. CHF induction by pacing was repeated in 4 dogs. Apical and basal rotations were measured using 2D speckle tracking, and LV twist was calculated as the difference between apical and basal rotations. Untwisting rate was calculated as the peak diastolic time derivative of LV twist.

Results
: CHF developed after 2–4 wks of pacing with LV end-diastolic volume (LVEDV), end-systolic volume (LVESV), end-diastolic pressure (LVEDP), and time constant of LV relaxation during isovolumic relaxation period (tau) all increasing significantly compared to baseline (Table

), and recovering to baseline levels 2–4 wks after pacing was stopped. LV twist and untwisting rate decreased with CHF compared to baseline, and improved during recovery from CHF although the change in untwisting rate between CHF and baseline was not significant. In pooled data, LV twist was significantly related to LVEDV (r=-0.60, P<0.001), LVESV (r=-0.59, P=0.001), LVEF (r=0.81, P<0.001), LVEDP (r=0.41, P=0.03) and +dp/dt (r=0.71, P<0.001), but not with end-systolic pressure (r=0.06, P=0.77). In multiple analysis, +dp/dt was the only independent predictor of twist (P < 0.001).

Conclusions
: LV twist dynamics can reflect the presence of pacing-induced CHF and its recovery. LV contractility appears to be the only determinant of LV twist in CHF.
Abstract 2477: Ventricular Synchrony can be Preserved by Right Ventricular Septal Pacing Compared with Right Ventricular Apical Pacing: Evaluation by Ultrasound Speckle-Tracking Imaging and Tissue Doppler Imaging
Authors: Izumi Chisato , Takahashi Shuichi , Hashiwada Sumiyo , Hayashi Hidetaka , Sakamoto Jiro , Higuchi Takahumi , Yoshitani Kazuyasu , Miyake Makoto , Motooka Makoto , Kaitani Kazuaki , Izumi Toshiaki , Gen Hiromitsu , Nakagawa Yoshihisa
Published: July 2021

Objectives:
Traditional right ventricular apical (RVA) pacing may induce ventricular dyssynchrony in patients with normal left ventricular (LV) function. The purpose of this study is to elucidate the influence of pacing sites on the ventricular dyssynchrony, using ultrasound speckle-tracking imaging and tissue Doppler imaging.

Methods:
We investigated 24 patients with normal LV function who underwent DDD pacemaker implantation. Right ventricular lead position was apex in 18 patients and septum in 6 patients. Radial strain and circumferential strain were measured using ultrasound speckle-tracking imaging (Vivid 7, GE) from short axis view at papillary muscle level. Myocardial velocity was measured by tissue Doppler imaging in mid-segments from apical 4-chamber view. The difference of time to peak radial strain, circumferential strain, and systolic myocardial velocity between septal and lateral wall were compared between during patients’ intrinsic rhythm and pacing rhythm, and between patients with RVA pacing and right ventricular septal (RVS) pacing.

Results:
In 18 patients with RVA pacing, difference of time to peak circumferential strain and systolic myocardial velocity between septal and lateral wall were larger during pacing rhythm than during patients’ intrinsic rhythm (circumferential strain: 118±57 vs 59±48msec, p<0.01, myocardial velocity: 75±47 vs 52±40msec, p<0.05). On the other hand, in 6 patients with RVS pacing, difference of time to peak radial strain, circumferential strain and systolic myocardial velocity during pacing rhythm were the same as those during patients’ intrinsic rhythm. Difference of time to peak circumferential strain between septal and lateral wall was smaller in patients with RVS pacing than patients with RVA pacing (37±50 vs 118±57msec, p<0.005).

Conclusions:
Ventricular synchrony can be preserved by RVS pacing compared with RVA pacing.
Abstract 2492: Clenbuterol, Unlike Other B
2
-Adrenoceptor Agonists, Predominantly Activates the G
i
Protein in Isolated Rat Ventricular Myocytes
Authors: Siedlecka Urszula , Arora Monica , Lee Joon , Stagg Mark A , Soppa Gopal , Harding Sian E , Yacoub Magdi H , Terracciano Cesare M
Published: July 2021

Clenbuterol (CLEN), a β
2
-adrenoceptor (AR) agonist, has been employed in combination with other pharmacological agents and LVADs to treat patients with severe heart failure (HF). Chronic administration of CLEN increases expression of Ca regulatory proteins in isolated cardiac myocytes and improves their contractility. However, the acute effects of CLEN on myocyte contractility compared to other β
2
-AR agonists and the signalling pathway of CLEN remain undefined. Here we compared the acute effects of CLEN to two other β
2
-AR agonists, fenoterol (FEN) and salbutamol (SAL). Isolated rat ventricular myocytes were superfused with β
2
AR agonists and sarcomere shortening was measured. CLEN produced a negative inotropism (30 μM: 65.3 ± 9.7% of control, n=9; p<0.05; 100 μM: 37.9 ± 8.0%, n=9; p<0.01) whereas FEN showed a positive inotropic response (30 μM: 184.8 ± 19.1% of control, n=9; p<0.01; 100 μM: 198.1 ± 20.5%, n=9; p<0.01). SAL had no significant effect. Selective β
1
AR blockade with 300 nM CGP 20712A did not affect CLEN’s action on sarcomere shortening but significantly reduced the contractile response to FEN and SAL (p<0.05). Additional blockade of β
2
AR-Gs with 50 nM ICI 118,551 unveiled a negative inotropic response to FEN (100 μM: 61.5 ± 7.3% of control, n=7; p<0.001) and SAL (100 μM: 67.4 ± 3.6% of control, n=7; p<0.01) and did not alter the response to CLEN. Incubation with 2 μg/ml pertussis toxin (PTX) almost abolished the negative inotropic effects of CLEN: 30 μM (PTX: 95.1 ± 4.9%, n=6 vs control: 73.9 ± 5.5%, n=7; p<0.05) and 100 μM (PTX: 96.2 ± 9.6%, n=6 vs control: 21.7 ± 5.5%, n=7; p<0.001), suggesting the involvement of the inhibitory guanine nucleotide binding protein (G
i
). In addition, overexpression of G
i
by adenoviral (AdV) transfection for 48 hrs induced a stronger negative inotropic effect upon application of CLEN compared with control cultured cells (AdV-Gi: clen 30 μM: 36.8 ± 8.3% of control, n=9; p<0.01; 100 μM: 19.7 ± 6.5%, n=9; p<0.01). In summary, CLEN significantly depresses contractility of ventricular myocytes, an effect not seen with FEN or SAL. CLEN predominantly acts through G
i
and the consequent downstream signaling pathways activation may explain the beneficial effects observed during administration of CLEN in patients treated with LVADs.
Abstract 2497: Does Magnitude of Heart Reduction Influence Clinical Outcomes in Patients with Systolic Chronic Heart Failure Receiving Beta-Blockers? A Regression Analysis of Randomised Controlled Trials
Authors: Flannery Genevieve , Gehrig-Mills Rosie , Billah Baki , Krum Henry
Published: July 2021

Background:
Beta-blockers (BBs) improve cardiac function and prolong survival in patients with systolic chronic heart failure (CHF). However, the exact mechanisms underlying these benefits are uncertain. Specifically, it is unclear whether a close relationship exists between heart rate (HR) reduction and clinical outcomes with these agents. We therefore tested this hypothesis within randomised controlled trials (RCTs) of BBs in systolic CHF.

Methods:
Left ventricular ejection fraction (LVEF) and HR values at baseline and end-study were obtained from available BB RCTs. The relationship between change in HR and all-cause mortality as well as LVEF was determined using regression analysis (SPSS).

Results:
Thirty-six trials, which included 23,122 patients with mean follow-up of 10.5 months, were analysed for all-cause mortality, LVEF and HR. There was a close relationship between all-cause annualised mortality rate and change in HR (adjusted R2=0.51, p=0.004). A strong correlation between change in HR and change in LVEF (adjusted R2=0.47, p=0.000, Figure

) was also observed. When only trials with >100 patients were included, an even tighter relationship was seen (adjusted R2=0.60, p=0.0004).

Conclusions:
These analyses indicate that a major contributor to the clinical benefits of BB therapy in systolic CHF is the HR-lowering effect of these agents. Therefore, magnitude of HR reduction may be more important than achievement of target dose in BB treatment of systolic CHF.
Abstract 2506: Long-Term Effect of Robotic-Assisted Left Ventricular Epicardial Leads for Cardiac Resynchronization Therapy on Mortality
Authors: Choi Andrew D , Kristof-Kuteyeva Olga , Garcia Wallacy , DeRose Joseph J , Balaram Sandhya , Steinberg Jonathan S
Published: July 2021

INTRODUCTION: In cardiac resynchronization therapy (CRT), our group has previously reported on positive clinical response and reverse remodeling using a novel robotically assisted left ventricular (LV) epicardial lead placement approach for pts with primary lead implant failure. In addition, CRT via transvenous approach is associated with an approximate 20% mortality rate at 18 mos. Long term mortality via robotic placement is unknown.

METHODS: We evaluated 71 pts (70 ± 11 yrs, 48 [68%] male) who underwent robotic LV lead placement after failed transvenous LV lead placement. Leads were placed based on Tissue Doppler Imaging to localize the site of latest mechanical activation. The Social Security Death Index was queried to identify mortality.

RESULTS: All pts had successful lead placement and were discharged in stable condition. During a follow-up (f/u) of 27 ± 16 mos, there were 18 deaths (25%) after 17.3 ± 14.5 mos (range 1.3 – 50.2 mos) (Figure

). These pts were older (77 ± 6 v. 68 ± 11 yrs; p < 0.001), with a lower EF (13 ± 7% v. 18 ± 9%; p < 0.05) and carried a greater symptom burden by NYHA class (3.6 ± 0.5 v. 3.1 ± 0.5; p = 0.02) when compared to those alive. There was no difference in pts with respect to HF duration, cardiomyopathy etiology or atrial fibrillation prevalence. A significant improvement in symptoms by NYHA class (3.1 ± 0.5 to 2.3 ± 0.7; p < 0.001) was seen at 8 ± 3 mos.

CONCLUSION: Pts undergoing robotic LV lead implant show symptomatic improvement, and have a similar mortality rate to transvenous placement during f/u. Those at greatest risk for death include older pts with a very low EF; risk/benefit for these pts should be carefully considered before undergoing implant.
Abstract 2523: Azelnidipine Enhances Beneficial Effects of Olmesartan on Left Ventricular Remodeling During the Development of Hypertension-induced Heart Failure
Authors: Cheng Xian Wu , Okumura Kenji , Nagata Kohzo , Inoue Aiko , Zhang Jie , Nishizawa Takao , Yamada Takashi , Murase Yosuke , Izawa Hideo , Asano Hiroyuki , Obata Koji , Kuzuya Masafumi , Shi Guo-Ping , Murohara Toyoaki , Yokota Mitsuhiro
Published: July 2021

Objective:
This work was undertaken to investigate the comparative effect of angiotensin II type 1 receptor blocker (ARB) and a combination of ARB and calcium channel blocker (CCB) on left ventricular (LV) remodeling during the development of hypertensive heart failure (H-HF).

Methods and Results:
We treated 8% salt-loaded Dahl salt-sensitive hypertensive rats (n = 10 for each group) with

vehicle,

hydralazine (5 mg/kg/d),

olmesartan (OLM, 5 mg/kg/d), or

combined OLM and azelnidipine (AZE, 2mg/kg/d) for 8 weeks.

The rats fed 0.3% salt served as age-matched controls. The abundance of Cat mRNAs and proteins were localized in cardiac myocytes (CMCs), and Cat-dependent activities were increased by 4.1-fold in the LV of H-HF rats (n = 8, P< 0.001) and were reduced by OLM treatment. OLM suppressed the elastic lamina degradation concomitant with decreased local Cat S expression in intracoronary smooth muscle cells (SMCs) and restored the balance of elastin to collagen in the LV tissue of H-HF rats (H-HF 4.6 ± 0.9% vs. OLM 15.5 ± 2.1% elastin content/collagen content (%), n = 6, P< 0.0±1; control 22±2.1%). OLM suppressed not only macrophage infiltration but also levels of NADPH oxidase components (p22
phox
, gp91
phox
, and p47
phox
) concomitant with decreased NADPH activity and O2- production in LV tissues of H-HF rats. Along with its comparable anti-inflammatory effect, add-on AZE further improved all of these parameter changes by OLM. Furthermore, combination therapy significantly enhanced the improvement of LV fibrosis, hypertrophy, stiffness, and dysfunction by OLM. In vitro, H
2
O
2
stimulated Cat S mRNA and protein expression and activity, and these increases were abolished by pretreatment with the antioxidants such as MnTmPyp (50 μmol/L) and N-acetylcysteine (5 mmol/L) as well as a NADPH oxidase inhibitor apocynin (100 μmol/L) in culture CMCs, SMCs, and macrophages (n = 6, P< 0.01).

Conclusions:
OLM and a combination of OLM and AZE exerted cardioprotective effects in hypertensive HF, via elastolytic Cat activation inhibition by the reduction of NADPH oxidase-dependent superoxide anion production. AZE enhanced the cardioprotective effects of OLM. Thus, the combination of ARB with CBB is a promising potential therapeutic strategy for H-HF.
Abstract 2526: Fetal Programming of Hypertension: Decreased Compliance and IGF-I Plasma Levels in Umbilical Arteries of Infants with Intrauterine Growth Restriction
Authors: Burkhardt Tilo , Matter Christian M , Lohmann Christine , Cai Hao , Lüscher Thomas F , Zisch Andreas H , Beinder Ernst
Published: July 2021

Background
: Epidemiological studies link intrauterine growth restriction (IUGR) to arterial hypertension in adulthood. Intrauterine stress may induce decreased arterial compliance that persists after birth, thus predisposing the individual for arterial hypertension in adult life.

Methods and Results
: We compared umbilical arteries from IUGR (n=13, <5
th
weight percentile) vs. appropriate for gestational age (AGA) infants (n=13) using structural and functional analyses. Vessel wall thickness and stiffness were determined in umbilical artery-derived vessel rings. Vessel wall elastin, the main determinant of arterial elasticity, was quantified by elastin extraction. Cord blood was assayed for growth factors known to modulate vessel wall matrix. IUGR infants had decreased umbilical artery compliance
in vivo
in terms of an increased resistance-index (P<0.05). In parallel, the vessel wall area of umbilical arteries in the IUGR group was significantly smaller than in the AGA group (2.8 vs. 3.8 mm
2
, P<0.05). Myographic measurements showed that maximal tension [mN/mm] as well as maximal force [mN] were both significantly increased in IUGR arteries compared with AGA arteries (P<0.05). Serum levels of IGF-I, a regulator of elastin synthesis, were significantly lower in IUGR cord blood (P<0.01) than in AGA cord blood. These IGF-I serum levels correlated significantly with maximum tension in umbilical arteries (P<0.01). In parallel, we found a trend to reduced elastin content in the vessel wall of IUGR vessels.

Conclusions
: IUGR infants possess thinner and stiffer umbilical arteries than AGA infants. Low intrauterine IGF-I serum levels may account for reduced arterial elastin at birth, thereby providing a potential link to arterial hypertension in adulthood.
Abstract 2541: The Impact of Arterial Remodeling on the Occurrence of Complicated Plaque Features: An in vivo MRI study
Authors: Saam Tobias , Underhill Hunter R , Chu Baocheng , Takaya Norihide , Cai Jianming , Nikolaou Konstantin , Reiser Maximilian F , Yuan Chun , Hatsukami Thomas S
Published: July 2021

PURPOSE: Positive Remodeling is considered to be a feature of the vulnerable atherosclerotic plaque. Via magnetic resonance imaging (MRI), we sought to determine the relationship between the prevalence of complex carotid atherosclerotic lesions (AHA-LT6+luminal surface defect, hemorrhage/thrombus or calcified nodule) and arterial remodeling.

METHODS&MATERIALS: 175 subjects with 1–99% stenosis as measured by duplex ultrasound had their bilateral carotid arteries imaged at 1.5T. After excluding arteries with previous endarterectomy or poor image quality, there were 260 arteries available for analysis. AHA-LT6, lumen, wall, total vessel (lumen=wall) areas and normalized wall index (NWI = wall area/total vessel area) were determined by the consensus opinion of 2 experienced carotid MRI reviewers.

RESULTS: There was a highly significant negative correlation between minimum lumen area
and
AHA-LT6, and highly significant positive correlations between maximum wall area / maximum NWI
and
AHA-LT6 (see Table

). No significant correlation between occurrence of complicated plaque features and maximum total vessel area was observed. Furthermore, arteries with AHA-LT6 had significantly smaller minimum lumen areas, larger mean wall areas and larger maximum NWIs than arteries without AHA-LT6 (p<.001). No significant difference between arteries with and without AHA-LT6 was found for the total vessel area.

CONCLUSIONS: Occurrence of complicated AHA Type VI lesions is related to arterial lumen
and
wall dimensions. The absence of a significant correlation between total vessel area and AHA Type VI lesions suggests that outward remodeling has a minor role in the development of these complicated lesions in carotid arteries.

Correlation of Quantitative Plaque Area Measurements with the Occurrence of Complicated Plaque Featu
Abstract 2560: Stent Thrombosis Predictors in Everyday Practice: Insights from the 7000-Patient TAXUS ARRIVE Registry Program
Authors: Lasala John M , Cox David A , Mascioli Stephen R , Baim Donald S
Published: July 2021

Background:
Risk factors associated with stent thrombosis (ST) of drug-eluting stents (DES) include acute coronary syndrome, stented length, and thienopyridine non-compliance. Predictive analyses for ST>30 days can be limited by low event numbers. The objective of this study was to identify baseline ST predictors at 1 and 2 years (yr) using a pooled analysis of >7000 registry patients (pts) to help guide individual pt therapy.

Methods:
Analysis included consecutively-enrolled pts (N=7307; 99 US sites) who received the TAXUS
®
Express
2
paclitaxel-eluting stent (Boston Scientific, Natick, MA) DES and were prescribed long-term aspirin and minimally 6 months (M) thienopyridine therapy per the product label. Events were adjudicated by an independent Clinical Events Committee using Academic Research Consortium (ARC) ST definitions. Over 30 baseline characteristics were assessed as potential predictors of ST using backward step-wise Cox proportional hazards regression.

Results:
Predictors for ST<1 yr and very late ST (VLST) differed except for discontinuation of thienopyridine before 6M, which was a strong predictor in both time intervals. For ST<1 yr predictors were based on lesion characteristics (calcification, long lesions, multiple stents in a vessel, and small vessels) as well as pt-related factors such as smoking at baseline and congestive heart failure. Predictors of VLST>1 yr included more biologic factors such as prior myocardial infarction and age. At time of event, 31% of VLST pts were on dual antiplatelet therapy; in contrast, 59% of ARRIVE pts overall continued thienopyridine therapy at 2 yrs.

Conclusions:
Differences in predictors for ST before and after 1 year suggest differences in pathophysiology. Dual antiplatelet therapy may be useful during year 2 after DES. Determination of DES baseline predictors may help identify pts at highest risk for late ST and VLST. Predictor analyses for high-risk subgroups in ARRIVE will be available in November.

Table 1.

Predictors of Stent Thrombosis in the TAXUS ARRIVE Registry
Abstract 2574: Accuracy of Apical Rotation by Two-dimensional Speckle Tracking Echocardiography is Influenced by Apical Slice Location.
Authors: Goffinet Celine , Chenot Fabien , Montant Patrick , Pouleur Anne-Catherine , le Polain de Waroux Jean-Benoît , Vancraeynest David , Pasquet Agnès , Gerber Bernhard , Vanoverschelde Jean-Louis
Published: July 2021

Background :
During the cardiac cycle, there is a systolic twist and an early diastolic untwist about LV long axis, because of opposite rotation of the basal and apical segments. Previous studies showed that speckle tracking echocardiography (STE) allows to measure the rotation of these segments and thereby to assess global LV torsion. Unfortunately, STE does not always allow visualization of the real apex, thus raising concerns about the reliability of LV torsion data using this approach.

Methods
: We compared LV apical rotation by tagged magnetic resonance (cMR) and STE in 30 patients with normal regional and global systolic function. With cMR, rotation was measured on serial contiguous 10 mm thick short-axis (SAX) sections, whereas with STE, it was only obtained on the most apical available SAX section. cMR and STE were compared using either the most apical cMR SAX slice or the cMR slice that best matched the end-diastolic internal dimensions of the available STE slice.

Results :
LV rotation measured by cMR decreased from apex to base (Fig 1

). When using the best matched cMR SAX slice, cMR and STE were well correlated (r=0.7, Fig 2

, black dots). By contrast, when using the most apical cMR SAX slice, the correlation between cMR and STE was lost (Fig 2

, white dots). By comparing end-diastolic internal dimensions, the level of the STE slice was found to be at the real apex in 10% of pts, and at 10, 20 and 30 mm below the apex in 27%, 50% and 13% of pts, respectively.

Conclusion :
Although STE allows to measure LV apical rotation, it rarely does so at the level of the real apex. This results in an almost systematic and mostly unpredictable underestimation of apical rotation.
Abstract 2585: Continuous Flow Left Ventricular Assist Devices (LVADs) Effectively Improve Pulmonary Hemodynamics in Bridge-to-Transplant Patients with End-Stage Heart Failure
Authors: Kamdar Forum , Boyle Andrew , Colvin-Adams Monica , Liao Kenneth , Joyce Lyle , John Ranjit
Published: July 2021

Introduction
: Pulmonary hypertension is a frequent sequelae of end-stage heart failure and remains a contraindication for cardiac transplantation. Pulsatile LVADs have been shown to effectively reduce pulmonary hypertension in these patients. However, it remains to be seen if newer continuous flow LVADs have a similar effect on pulmonary hypertension. The objective of this study was to determine if the Heartmate (HM) II, a continuous flow LVAD is effective in improving pulmonary hemodynamics in bridge-to-transplant patients.

Methods
: 30 patients with end-stage heart failure underwent placement of HM II LVAD as a bridge-to-transplant (BTT) at a single center. Pulmonary hemodynamics were evaluated with right heart catheterization at baseline, after placement of an intra-aortic balloon pump (IABP), and post-LVAD (prior to heart transplant).

Results
: Demographic data of these patients were as follows: mean age 51.6 ± 13.3 years, 70% male, LVEF 14.7 ± 5.11%, 56.6% ischemic etiology and 83.3% received IABP prior to LVAD. Following LVAD support (mean duration of 146. 41 ± 73.83 days), systolic and diastolic pulmonary artery pressures (SPAP and DPAP) decreased significantly (SPAP 56.8 ± 13.55 mmHg, DPAP 28.27 ± 6.23 mmHg to SPAP 35.38 ± 10.23 mmHg, DPAP 15.71 ± 5.36 mmHg; p < 0.001). Similarly, pulmonary vascular resistance (PVR) decreased significantly from 3.69 ± 2.02 to 2.00 ± 0.85 Woods units (p = 0.004). Transpulmonary gradient (TPG) also declined significantly post-LVAD from 13.3 ± 5.6 to 9.35 ± 2.98 mmHg (p = 0.02).

Conclusion
: Continuous flow LVADs effectively improve pulmonary hemodynamics associated with end-stage heart failure. Therefore, adequate left ventricular decompression achieved with continuous flow LVAD support can reverse significant pulmonary hypertension in end-stage heart failure patients making them eligible for cardiac transplantation.
Abstract 2586: Tricuspid Valve Repair During Left Ventricular Assist Device Insertion
Authors: Comas George , Glithero Kyle J , Naseem Tariq , Jan Azam , Naka Yoshifumi
Published: July 2021

Purpose Right ventricular (RV) failure is associated with significant post-operative morbidity and mortality after left ventricular assist device (LVAD) insertion. Concomitant tricuspid valve repair (TVR) in the setting of tricuspid regurgitation (TR) is frequently performed to improve RV function after LVAD insertion. This study compared outcomes of patients with TR after LVAD insertion with and without TVR.

Methods This was a retrospective case control study of 70 patients with matched degrees of TR undergoing LVAD implantation from 2000 to 2006 (Heartmate1, Heartmate2, DeBakey MicroMed). The TVR group consisted of patients undergoing LVAD insertion with TVR (n=24). The control group consisted of patients undergoing LVAD insertion without TVR (n=46). TR was quantified as 0 (none) to 4+ (severe) on echocardiography preoperatively and postoperatively. RV dysfunction score was defined as 0 (none), 1 (mild), 2 (moderate), or 3 (severe) on echocardiography. Postoperative clinical parameters, complications, and outcomes were evaluated.

Results The TVR group and control group were similar in age (55y±15 vs 53y±12 respectively), gender distribution (18/24 male vs 42/46 male), ejection fraction (16%±5 vs 16%±6), LVAD score (preoperative measure of risk assessment 0–10), TR, mean PAP, CVP, and peak RV systolic pressure. In the TVR group, TR decreased from 2.0±0.8 to 0.7±0.5 post-operatively (p<0.001). In the control group, TR also decreased from 2.2±0.7 to 1.3±0.8 (p<0.001). In the TVR group, RV dysfunction score fell from 2.1±0.6 to 1.4±1.0 (p=0.01). In the control group, RV dysfunction score fell from 2.1±0.8 to 0.8±1.1 (p=0.049). Bypass time was higher in the TVR group (124±33min vs 66±46min). Incidence of acute renal failure (ARF) was lower in the TVR group (OR 0.2, p=0.02). There were no differences between the two groups regarding need for post-operative RVAD, early extubation, ICU LOS, bridge to transplant rate, or 30 day mortality.

Conclusion Patients with TR requiring LVAD insertion had no improved survival when TVR was performed simultaneously. Bypass time was prolonged when TVR was performed. Patient groups with and without TVR had similar decreases in TR and improvement in RV dysfunction. Incidence of ARF was lower in the TVR group.