bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13618: Negative Association of H558r Polymorphism and Ventricular Fibrillation in Patients With Brugada Syndrome
Authors: Matsumura Hiroya , Nakano Yukiko , Toshishige Masaaki , Ochi Hidenori , Tokuyama Takehito , Watanabe Yoshikazu , Kawazoe Hiroshi , Tomomori Shunsuke , Kishimoto Sinji , Chayama Kazuaki , Kihara Yasuki
Published: July 2021

BACKGROUND:
The common
SCN5A
polymorphism H558R has been reported as a genetic modulator that improves sodium channel activity in mutated channels by repairing abnormal channel gating kinetics and membrane trafficking. We investigated the possible effects of H558R on the clinical manifestations of Brugada syndrome.

METHODS:
The study population comprised 95 Brugada syndrome patients (mean age 42 ± 14 years, 91 males and 4 females) and 1,875 normal controls. H558R was genotyped by TaqMan assay in all subjects. The
SCN5A
gene mutation was screened by resequencing. We evaluated the PR, QRS, and QTc intervals from lead II and the J-point amplitude from leads V1 and V2 of a 12-lead electrocardiogram (ECG). We also evaluated signal-averaged ECG and electrophysiological parameters.

RESULTS:
H558R was less frequent in patients with Brugada syndrome than normal controls (4.7% vs. 10.3%, P = 0.01). Surprisingly, H558R (minor allele A) was not observed in patients with Brugada syndrome without ventricular fibrillation (VF; n = 60), whereas 7.5% of patients with VF had H558R (n = 35). Nonsynonymous mutation of
SCN5A
was not detected in patients with H558R. The H558R carriers showed lower J-point elevation in lead V1 than noncarriers (1.8 ± 0.4 vs. 3.3 ± 0.3 mV, P = 0.04).

Other parameters in the 12-lead and signal-averaged ECG were similar in patients with and without H558R.

CONCLUSION:
We demonstrated that the H558R polymorphism was a strong protective genetic modulator even in Brugada syndrome patients without
SCN5A
mutation.
Abstract 13640: Dapagliflozin Lowers HbA1c, Systolic Blood Pressure and Serum Uric Acid in Patients With Type 2 Diabetes and Hypertension, Regardless of Class of Concomitant Antihypertensive Therapy
Authors: Weber Michael A , Mansfield Traci A , Iqbal Nayyar , Parikh Shamik J , Ptaszynska Agata
Published: July 2021

Hypertension (HTN) in Type 2 diabetes (T2D) is often treated with an ACEi/ARB + additional antihypertensives agents (AHTs). Dapagliflozin (DAPA) is an inhibitor of sodium glucose co-transporter 2, reducing hyperglycemia in T2D by increasing urinary glucose excretion. This is associated with weight reduction, osmotic diuresis and serum uric acid reduction, all of which may contribute to BP lowering. This Phase 3 study assessed 12 weeks of DAPA 10 mg (N=225) or placebo (PBO; N=224) in T2D patients (HbA1c 7.0-10.5%) with HTN (seated SBP / DBP 140 - <165 / 85 - <105 mmHg) receiving glucose-lowering drugs, an ACEi/ARB, + an additional AHT: β-blockers (27%), Ca-channel blockers (CCBs; 27%), thiazide/thiazide-like diuretics (diuretics; 44%) or α-adrenergic antagonists (α-AAs; 1%). Main results were presented previously. Here we describe treatment effects according to the additional AHT (α-AA group not analyzed due to small sample size). Patients were randomized to DAPA 10 mg or PBO, stratified by insulin use and diuretics vs CCBs/β-blockers/α-AA. Baseline characteristics were similar for DAPA vs PBO. Reduction in HbA1c and mean 24-hour ambulatory SBP was greater with DAPA vs PBO overall, and appeared greater with DAPA vs PBO in all AHT sub-groups (Fig). Reduction in seated SBP was greater with DAPA overall (diff vs PBO; –4.28 [95% CI: –6.54, –2.02] mmHg) and also appeared greater with DAPA in sub-groups (diff vs PBO: β-blockers –5.76 [–10.28, –1.23]; CCB –5.13 [–9.47, –0.79]; diuretics –2.38 [–6.16, 1.40] mmHg). Serum uric acid decreased more with DAPA overall (diff vs PBO; –0.40 [95% CI: –0.57, –0.23]), and was observed to decrease more with DAPA in sub-groups (diff vs PBO: β-blockers –0.62 [–0.95, –0.29]; CCBs –0.33 [–0.65, –0.01]; diuretics –0.22 [–0.49, 0.05] mg/dL). DAPA was well tolerated; AEs were similar for DAPA (44%) vs PBO (42%). In summary, regardless of the concomitant AHT, DAPA reduced HbA1c, SBP and serum uric acid vs PBO in patients with uncontrolled T2D and HTN.
Abstract 13691: Right Ventricular Remodeling Post MitraClip Insertion for Severe Mitral Regurgitation - Single Centre Echocardiographic Study
Authors: Anvardeen Kalilur , Yamen Eric , Passage Jurgen , Finn Chris , McQuillan Brendan
Published: July 2021

Introduction:
Percutaneous mitral valve repair (Mitraclip) has expanded treatment options for high risk surgical patients with severe mitral regurgitation (MR).

Hypothesis:
The impact of amelioration of MR by Mitraclip on right ventricular (RV) remodeling and the pulmonary vasculature has received limited investigation.

Methods:
We undertook a prospective evaluation of consecutive patients who underwent Mitraclip insertion at our centre. Transthoracic echocardiograms were performed pre Mitraclip, 1 day, 1 month, 6 months and 12 months post Mitraclip procedure. We assessed right ventricular (RV) size, fractional area change (FAC), Myocardial performance index (MPI), right atrial (RA) area, left ventricular ejection fraction (LVEF), and estimated pulmonary artery systolic pressure (PASP) from the tricuspid regurgitant spectral Doppler signal according to published ASE guidelines.

Results:
Twenty-nine patients underwent Mitraclip procedure from March 2011 to June 2013. Six patients were excluded from 12 month analysis because of incomplete data (2 patients), insertion of a LV assist device (1), and mortality (3), Among the 23 study patients, mean age was 73 y (range 52 to 85). The following table shows the mean values and standard errors with significant differences indicated in * (p<0.05), ** (p<0.01) Linear mixed effects models were used to compare pre treatment measurements with post treatment measurements.

Conclusion:
Right ventricular function by FAC and MPI improved post Mitraclip. Pulmonary artery pressures also improved although the benefit appeared limited to 6 months post procedure. We observed no clear change in other parameters of right heart function or chamber size. Larger long term studies are required to evaluate these results.
Abstract 13697: Glucagon-like Peptide-1 Analogue Liraglutide Does Not Improve Microvascular Myocardial Function in Patients With Type 2 Diabetes - a Randomized, Single-blinded Cross Over Trial
Authors: Faber Rebekka , Zander Mette , Pena Adam A , Michelsen Marie M , Mygind Naja D , Prescott Eva
Published: July 2021

Background:
Impaired coronary microcirculation is associated with a poor prognosis in patients with type 2 diabetes. In the absence of stenosis of major coronary arteries, coronary flow reserve (CFR) reflects coronary microcirculation. Studies have shown beneficial effects of glucagon-like peptide-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes.

Methods:
Twenty patients with type 2 diabetes and no history of coronary artery disease were treated with the GLP-1 analogue Liraglutide for 10 weeks, in a randomized single-blinded crossover setup. The effect of GLP-1 on coronary microcirculation was evaluated using non-invasive trans-thoracic Doppler-flow echocardiography during dipyridamole induced stress. Data were analysed as two-sample t-test after ensuring no carry over effect.

Results:
A total of 20 patients (15 male; mean age 57 ± 9; mean BMI 33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45) completed full protocol. There was a small increase in CFR following GLP-1 treatment (change 0.18, CI95% [-0.01; 0.36], p=0.06) but with no difference in effect compared with the no treatment group (0.16, CI95% [-0.08; 0.40], p=0.18). GLP-1 significantly reduced glycated haemoglobin (-10.1 mmol/mol CI95% [-13.9; -6.4], p=<0.001) systolic blood pressure (-10 mmHg CI95% [-17; -3], p=0.01) and weight (-1.9 kg CI95% [-3.6; -0.2], p=0.03).

Conclusion:
Despite a significant weight-loss, reduction in HbA1c and systolic blood pressure, we did not find a significant improvement in coronary microcirculation after 10 weeks treatment with GLP-1. In our short-term treatment study, we therefore conclude that the GLP-1 analogue Liraglutide does not improve coronary microcirculation in patients with type 2 diabetes. Further long-term studies are needed to explore mechanisms to improve coronary microcirculation in patients with type 2 diabetes.
Abstract 13729: Surgical Myectomy Results in Significantly Improved Long-term Event Rate in Hypertrophic Cardiomyopathy Patients With Severe Left Ventricular Outflow Tract Obstruction
Authors: Desai Milind Y , Smedira Nicholas G , Bhonsale Aditya , Ainani Nitesh , THamilarasan Maran , Lytle Bruce , Lever Harry
Published: July 2021

Background:
In hypertrophic cardiomyopathy (HCM) with severe left ventricular outflow tract obstruction (LVOTO), surgical myectomy (SM) performed for relief of intractable symptoms is safe and associated with excellent long-term symptom-free survival. In such patients, we sought to determine if SM also results in improvement of long-term outcomes.

Methods:
We studied 1530 HCM patients with severe LVOTO (50±13 years, 63% men) that were evaluated at our center [excluding <18 years of age, LV ejection fraction (LVEF) <50%, LVOT gradient <30 mm Hg). Clinical, echocardiographic and surgical data were recorded. A composite endpoint of death and/or implantable defibrillator (ICD) discharge was recorded.

Results:
Hypertension, coronary artery disease (CAD), family history of HCM and syncope were present in 41%, 15%, 17% and 18%, while 73% patients were in Functional Class (FC) ≥ II. Mean LVEF, basal septal thickness, LVOT gradient (resting or provocable) and indexed left atrial dimensions were 62±5%, 2.2±1 cm, 101±39 mm Hg, 2.2±0.4 cm/m2. During 8±6 years of follow-up, 990 (65%) patients underwent SM (of which 65% were isolated SM), while 540 (35%) did not. 94 (6%) patients had alcohol septal ablation (66 in the non myectomy group), while 18% developed atrial fibrillation (AF), and 18% had ICD. There were 169 (11%) events (151 deaths), with 0% 30-day mortality in the SM group. On stepwise multivariable Cox Proportional Hazard analysis, increasing age (Hazard Ratio or HR 1.22 [1.06-1.40]), CAD (HR 1.57 [1.06-2.33]), worsening FC (HR 1.34 [1.05-1.71]) and AF (HR 1.73 [1.23-2.43]) predicted higher events, while SM as a time-dependent covariate (HR 0.58 [0.41-0.81]) was associated with improved event-free survival (all p<0.01). Kaplan-Meier curve showing impact of SM on outcomes is shown in Figure.

Conclusion:
In HCM patients with severe LVOTO, SM is associated with significant improvement in long-term outcomes when compared to watchful waiting.
Abstract 13745: Severity of Functional Mitral Regurgitation During Maximal Exercise Testing in Heart Failure: Additional Value of Combining Echocardiography with Cardiopulmonary Exercise Testing
Authors: Generati Greta , Bandera Francesco , Pellegrino Marta , Labate Valentina , Alfonzetti Eleonora , Guazzi Marco
Published: July 2021

Background:
In heart failure (HF) patients the severity of mitral regurgitation (MR) at rest has a well established prognostic value and its increase during exercise further adds to an increased risk. Our goal was to define the relationship between the degree of exercise MR severity with cardiopulmonary and echocardiographic related phenotypes in a cohort of HF patients.

Methods:
71 HF reduced ejection fraction patients (mean age 67±11; male 72%; ischemic etiology 61%; NYHA class I, II, III and IV 13%, 36%, 39% and 12%, mean ejection fraction 33±9%) underwent cardiopulmonary exercise test (CPET) on tiltable cycle-ergometer combined with echocardiography at rest and during exercise. The population was divided into two groups according to the degree of functional peak MR: no to mild/moderate MR (no MR, MR1+ and MR2+) vs moderate/severe MR (MR3+ and MR4+).

Results:
A good correlation (ρ coefficient= 0.49) was found between the degree of dynamic MR and PASP at peak exercise. Despite similar echocardiographic profile at rest patients with significant peak MR (MR≥3+) had worse exercise performance (lower peak VO2, O2 pulse and workload) and impaired ventilatory efficiency (higher VE/VCO2 slope).

Conclusions:
In HF patients the severity of exercise-induced MR is associated with the most unfavorable performance and pulmonary hemodynamic response. A combined approach with CPET and echocardiographic assessment can help to early unmask and target functional MR and its related unfavorable phenotypes.
Abstract 13767: Thymosin β4 and its Cleavage Product Ac-SDKP Are Down-regulated in Left Ventricular Myocardium of Dogs with Chronic Heart Failure
Authors: Gupta Ramesh C , Wang Mengjun , Zhang Kefei , Sing-Gupta Vinita , Sabbah Hani N
Published: July 2021

Background:
Thymosin β4 (Tβ4) is a 43 amino acid peptide and has been shown to promote angiogenesis, suppress pro-inflammatory cytokines and protect cardiomyocytes from apoptosis and oxidative stress injury. The Tβ4 cleavage product Ac-SDKP is a tetrapeptide (Acetyl-Ser-Asp-Lys-Pro) that has been shown to inhibit collagen production by fibroblasts and collagen deposition in the LV of rats with hypertension or myocardial infarction. In the setting of chronic heart failure (HF), LV dysfunction and chamber remodeling are associated with interstitial fibrosis, reduced capillary density, cardiomyocyte apoptosis and increased production of reactive oxygen species (ROS).

Hypothesis:
This study tested the hypothesis that protein levels of both Tβ4 and its cleavage product Ac-SDKP are down-regulated in LV myocardium of dogs with advanced chronic HF.

Methods:
LV tissue was obtained from the LV free wall of 6 normal dogs and 6 dogs with chronic HF (LV ejection fraction ~30%) produced by multiple sequential intracoronary microembolizations. Protein levels of Tβ4 and β-actin, as internal control, were determined by Western blotting and bands expressed in densitometric units (du). Levels of Ac-SDKP were determined by ELISA and expressed in ng/mg protein.

Results:
Protein level of β-actin did not change significantly between normal dogs (1.34 ± 0.19 du) and dogs with chronic HF (1.22 ± 0.18 du). Protein level of Tβ4 was significantly lower in LV myocardium of dogs with HF compared to normal dogs (0.36 ± 0.06 vs. 1.64 ± 0.13 du, p<0.05). Similarly, levels of Ac-SDKP were significantly lower in LV myocardium of HF dogs compared to normal dogs (93 ± 9 vs. 155 ± 4 ng/mg protein, p<0.05).

Conclusions:
Protein levels of Tβ4 and its cleavage tetrapeptide Ac-SDKP are markedly down-regulated in LV myocardium dogs with chronic HF. These findings are in-line with the reported increase of pro-inflammatory cytokines, interstitial fibrosis, cardiomyocyte apoptosis, and ROS formation as well as reduced capillary density in the failing LV myocardium of dogs with microembolization-induced HF as well as patients with HF. The findings support the therapeutic targeting of Tβ4 and Ac-SDKP as potential treatment for chronic HF.
Abstract 13786: Contribution of Medications and Risk Factors to QT Interval Lengthening in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Alburikan Khalid A , Savitz Samuel T , Whitsel Eric A , Tisdale James E , Soliman Elsayed Z , Thudium Emily M , Sueta Carla A , Kucharska-Newton Anna M , Stearns Sally C , Rodgers Jo E
Published: July 2021

Objective:
Prolongation of corrected QT interval (QTc) is associated with increased morbidity and mortality, but the association between the number of QT interval prolonging medications (QTPMs) versus selected non-pharmacologic risk factors on the magnitude of QTc lengthening is unknown. We examined these associations in a longitudinal study of a population-based cohort.

Methods:
We included 15,792 ARIC participants with a resting, standard 12-lead electrocardiogram and ≥ 1 measure of QTc over up to four triennial examinations between 1987 and 1998 (54,638 person-visits). Participants with QRS > 120 ms were excluded (n=2,333). To optimize clinical applicability, QTc was calculated using Bazett’s equation. At each visit, we identified participants using ≥ 1 AzCERT-classified QTPMs, age > 65 years, females, and those with left ventricular hypertrophy (LVH), or QTc > 500 ms at the prior visit. We used linear regression for 36,513 person-visit observations from visits 2-4 to examine QTc lengthening associations. Visit indicators were controlled for time, and standard errors were corrected for repeat observations per person.

Results:
Use of any QTPM increased from 9% to 17% between visits 1 and 4 and occurred more frequently among females and participants with LVH. Among person-visit observations from Visit 2-4, 70% (n=25,513) had at least one risk factor including age > 65 years (25%), female sex (56%), LVH (8%) and QTc>500 ms (1%). In patients receiving no QTPM, female sex was associated with the greatest QTc lengthening at 13 ms [95% CI 12-13] followed by LVH at 7 ms [6-9], QTc > 500 ms at 7 [4-10], and age > 65 at 2 ms [1-3]. Mean QTc increased with increasing number of QTPMs and risk factors (Table). The greatest QTc lengthening occurred in participants using ≥ 2 medications with ≥ 1 risk factor.

Conclusions:
Risk factors, particularly female sex, contribute more to QTc lengthening than QTPMs.
Abstract 138: Remote Ischemic Postconditioning Alleviates Postresuscitation Inflammatory Response and Pulmonary Edema in a Porcine Model of Cardiac Arrest
Authors: Xu Jiefeng , Ye Sen , Li Zilong , Wang Moli , Wang Zhengquan , Chen Guofeng , Tang Wanchun
Published: July 2021

Introduction:
Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model.

Hypothesis:
RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA.

Methods:
Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs.

Results:
Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table).

Conclusion:
In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.
Abstract 13830: Impact of Atrial Fibrillation on Clinical Outcome of Femoropopliteal Artery Intervention in Critical Limb Ischemia
Authors: Jinnouchi Hiroyuki , Soga Yoshimitsu , Kobayashi Yohei , Tomoi Yusuke
Published: July 2021

Introduction:
Clinical outcome of patients with atrial fibrillation (AF) after endovascular therapy for critical limb ischemia (CLI) is unclear. The aim of this study was to investigate if atrial fibrillation (AF) influences clinical outcomes after femoropopliteal artery intervention in patients with CLI.

Methods:
A retrospective review of all patients undergoing femoropopliteal artery intervention for CLI was performed. We compared clinical outcome between patients with and without AF. The primary endpoint was amputation free survival (AFS). The secondary endpoints were overall survival, limb salvage, freedom from repeat revascularization, and freedom from surgical conversion were compared between two groups. Kaplan-Meier analyses were performed to assess time-dependent outcomes. Factor analyses were performed using a Cox proportional hazard model for time-dependent variables.

Results:
A total of 398 limbs with 342 patients were performed with femoropopliteal artery intervention in patients with CLI. (male 58.4%, 73.9±10.8 years old, mean follow up 17 months; interquartile range 5-32 months). We identified 58 limbs with AF, 340 without AF. At median follow-up period, AFS and overall survival was significantly lower in patients with AF (51.0 % vs 70.5 % P=0.0004 by log-rank, 53.9 % vs 77.1 % P<0.0001; relatively). Other outcomes were not significantly different between the groups. Risk-adjusted Cox proportional hazards regression showed that AF predicts poor AFS and overall survival (hazard ratio [HR], 1.59; 95% confidential interval [CI] 1.01-2.43; adjusted P=0.044, HR, 1.89; 95%CI, 1.19-2.98; adjusted P=0.008).

Conclusion:
AF may worse AFS and overall survival rate in patients who underwent femoropopliteal intervention in CLI.
Abstract 13863: Stress Echocardiography in Asymptomatic Patients: Impact of Clinical Risk Profile on Test Results
Authors: Calvin Andrew D , Arruda-Olson Adelaide M , Pellikka Patricia A , Scott Christopher G , McCully Robert B
Published: July 2021

Introduction:
Stress echocardiography (SE) has an established role in the evaluation of symptomatic patients, but its utility in asymptomatic patients is unclear. Current guidelines discourage the use of SE in most asymptomatic patients, citing lack of data to support its use. We therefore sought to describe the yield of SE in a group of asymptomatic individuals according to risk profile.

Hypothesis:
We hypothesized that SE would rarely be abnormal in asymptomatic individuals.

Methods:
We conducted a retrospective cohort study of all asymptomatic individuals who underwent exercise or pharmacologic SE between 2003 and 2013. Reasons for SE included screening for CAD, preoperative evaluation, abnormal ECG, coronary calcification, and assessment of established CAD (defined as prior myocardial infarction or coronary revascularization). We grouped subjects using both the 10-year Framingham risk equation and ATP3-suggested categories of low-risk (<10%), intermediate-risk (10-20%), and high-risk (>20%) for non-diabetic subjects without known CAD and by ACC/AHA Pooled Cohort risk estimates for subjects with and without diabetes. Subjects with established CAD were considered separately. Abnormal echocardiograms were defined as having ischemic, fixed, or mixed defects.

Results:
The study population comprised 19,170 subjects; 63% men, mean±SD age was 64±13 years, and 52% underwent pharmacologic SE. The likelihood of abnormal SE results was proportional to risk, with the highest yield in those with established CAD (59%). Those with diabetes had a yield similar to those with a 10 year risk of 10-20% by both ATP3/FRS and ACC/AHA.

Conclusions:
SE abnormalities are commonly seen in asymptomatic individuals; the likelihood of abnormal SE results was proportional to patients’ estimated risk. The frequency of SE abnormalities in diabetic patients is similar to that of intermediate-risk, but not high-risk patients.
Abstract 13873: Quantitative Characteristics of Left Ventricular Vortex Flow in the Short and Long Axis Views by High Frame Rate Echocardiographic Particle Image Velocimetry
Authors: Abe Haruhiko , Masuda Kasumi , Asanuma Toshihiko , Koriyama Hikaru , Koretsune Yukihiro , Kusuoka Hideo , Nakatani Satoshi
Published: July 2021

Background:
Vortex flow in the left ventricle (LV) has three-dimensional structure and plays an important role in avoiding excessive dissipation of energy. However, quantitative characteristics of long and short axis (LAX and SAX) vortex flow have not been elucidated. Echocardiographic particle image velocimetry (Echo-PIV) is an emerging technique to evaluate instantaneous vortical flow inside the LV. However, it has a limitation of underestimation of high velocities due to limited frame rate. Moreover, previous investigations have mainly focused on vortex from LAX view. Therefore, we used high frame rate Echo-PIV to quantitate vortex flow in SAX as well as in LAX views to understand characteristics of vortex three-dimensionally.

Methods:
Echocardiographic contrast images of the LV SAX and LAX were acquired from 8 open-chest healthy dogs. The acquisition frame rate was 135 frames per second and the contrast bubbles density was optimized for blood flow analysis. Echo-PIV analysis was performed off-line by using commercially available software and vorticity data were calculated in the region of interest (ROI) throughout the cardiac cycle. ROI was manually placed on the vortex. Vortex strength was defined as the averaged vorticity within the ROI.

Results:
In SAX, counterclockwise vortex was seen near the anterior wall, and in LAX clockwise vortex was seen in the anterior mid-ventricle. Both in SAX and LAX views, vortex strength showed significant phasic variations being largest in isovolumic contraction (vortex strength, SAX 9.2±2.3/s, p<0.001; LAX -12.0±2.4/s, p<0.001), and smallest in isovolumic relaxation (SAX -0.8±0.8/s, p<0.001; LAX -1.9±1.9/s, p<0.001).

Conclusion:
High frame rate Echo-PIV successfully demonstrated a complicated pattern of intracardiac vortex with phasic variation of its strength throughout a cardiac cycle in both SAX and LAX. This method may be a useful tool to assess physiological role of vortex in the flow dynamics.
Abstract 13946: Sleep Problems on Simvastatin Differentially Predict Weight Change in Men
Authors: Golomb Beatrice A , Koslik Hayley J , Bui Alexis K
Published: July 2021

Background and Goal:
Sleep problems were significantly increased on simvastatin (
simva
) (but not pravastatin) vs placebo in the UCSD Statin Study. Sleep problems on simva predicted glucose rise. Weight gain has also been reported as a statin side effect. We sought to capitalize on existing data to assess whether sleep problems on simva related to weight gain in men.

Method:
442 men without known diabetes or CVD were randomized to simva 20mg or placebo for 6 mon. One hundred eighty and 186 completed single-item self-rating of change in sleep problems vs baseline (
Δslpprob
). Weight (lb) was measured at baseline and 6 mon. Missing 6 mon values were imputed.

Analyses:
A. Regressions stratified by treatment assessed prediction of weight change by Δslpprob, adjusted for baseline weight. B. Regressions assessed prediction of weight change by the interaction term of simva (vs placebo) x Δslpprob, adjusted for the components of the interaction and baseline weight. Since age-related muscle loss may complicate weight change in elderly; and young adults have low vulnerability to metabolic problems, analyses were repeated excluding these groups.

Results:
A. Increased sleep problems on simva predicted weight
gain
(significant), but on placebo predicted weight
loss
(nonsignificant). B. The Δslpprob x simva interaction term significantly predicted weight gain. When that was parceled out, simva, outside of the sleep relationship, negatively predicted weight change. Exclusion of young adults and elderly strengthened significance of findings (Table).

Discussion:
Sleep problems, which differentially arise on simva, differentially predict weight gain on simva. This expands the metabolic effects to which sleep problems on simva may contribute and might possibly favor mediation by sleep apnea (a reported complication of simva). Once the sleep problem effect is considered, simva use predicted weight
loss
. The relative contribution of fat vs muscle loss (vs other) requires exploration.
Abstract 13957: Vagal Nerve Stimulation Mitigates Atrial Fibrillation by Attenuating the Intrinsic Cardiac Local Circuit Neuronal Activity
Authors: Salavatian Siamak , Beaumont Eric , Longpre Jean-Philippe , Vinet Alan , Jacquemet Vincent , Armour John A , Ardell Jeffrey L
Published: July 2021

Background:
Burst electrical stimuli delivered to intra-pericardial mediastinal nerves (MNS) during the atrial refractory period reproducibly evoke atrial fibrillation (AF), an effect dependent upon heterogeneous activation of intrinsic cardiac (IC) neurons. The objective of this study was to determine whether pre-emptive vagus nerve stimulation (VNS) alters MNS-induced neuronal imbalance within the IC neurons thereby impacting susceptibility to AF.

Methods:
Activities of right atrial ganglionated plexus neurons were identified in anesthetized canines (n=11) using a linear microelectrode array. IC neuron activity was characterized in response to: 1) touch and great vessel occlusion versus (2) stellate ganglion or vagal stimulation. Right MNS was evaluated in relation to evoked IC activity and the potential to induce atrial tachyarrhythmias. Responses were assessed prior to and after pre-emptive left (LCV) or right (RCV) cervical VNS (15 Hz, 500 μs; 1.2x chronotropic threshold; 3 min).

Results:
In control, 100% MNS sites induced AF. Pre-emptive RCV VNS prevented MNS-induced AF induction from 37% of sites; it shortened AF duration in 56% of sites. Pre-emptive LCV VNS potentiated AF in 46% of right-sided MNS sites, prevented AF in 27% of sites, shortened AF in 7% of sites; it was without effect in 20% of sites. Pre-emptive VNS induced a memory effect of ~40 minutes before the MNS-induced AF returned. VNS effects on IC neuronal responses were related primarily to neurons that responded to both touch/vessel occlusion and efferent activation, as such being defined as local circuit neurons (LCNs). A RCV VNS related decrease in IC LCNs activity (0.61±1.83 to 0.16±0.57 Hz) was correlated with reduction in AF inducibility (p<0.05). Chi-square analysis indicated that an increase in LCN neuronal synchrony during MNS-induced AF was mitigated post VNS (p<0.01).

Conclusions:
VNS decreases the activity of the IC LCNs while maintaining their stochastic behavior, thereby mitigating AF excitability secondary to local neural imbalances. These anti-arrhythmic effects of VNS exhibit memory. Ipsilateral VNS projections more effectively stabilize discrete IC neuronal networks, likely owing to preferential nerve distributions.
Abstract 13982: Derivation of Functional Smooth Muscle Cells From Integration-free Induced Pluripotent Stem Cells Through Cardiovascular Progenitor Cell Intermediates for Vascular Regeneration
Authors: Wang Yongyu , Hu Jiang , jiao Jiao , Zhou Zhou , Chen Eugene Y , Ma Peter , Yang Bo
Published: July 2021

Tissue-engineered blood vessels (TEBVs) hold great promise for replacement of damaged or defective vascular tissues in vascular disease therapies, such as coronary and peripheral bypass graft surgeries. However, it remains a great challenge to obtain sufficient numbers of functional smooth muscle cells (SMCs) in the practice of constructing patient-specific TEBVs. This study aimed to develop an efficient method to generate a large number of functional SMCs in a short term for constructing tissue-engineered vascular tissues. Human induced pluripotent stem cells (iPSCs) were established by integration-free episomal vector-based reprogramming of donor peripheral blood mononuclear cells (PBMCs). These established iPSCs expressed pluripotency markers and were demonstrated to be able to differentiate into all three germ layer cells. Cardiovascular progenitor cell (CVPC) intermediates were then promptly and efficiently induced and expanded in chemically defined medium. Vascular smooth muscle cells (SMCs) were further induced under differentiation condition, which expressed typical SMCs markers including smooth muscle α-actin (α-SMA), calponin and SM22α validated by quantitative real-time PCR and immunocytochemistry stain. Importantly, the derived SMCs showed functional properties, validated by contraction responsiveness to carbachol treatment, up-regulation of specific collagens gene expression under transforming growth factor β1 treatment and up-regulation of specific matrix metalloproteinases gene expression under cytokine stimuli. Future studies will be focused on using these functional SMCs to construct functional TEBVs on biomimetic scaffolds. Taken together, our study established a facile procedure to generate large amount of functional and safe SMCs for vascular regeneration, via establishment of donor-specific integration-free human iPSCs and directed differentiation through CVPC intermediates.
Abstract 14035: Autophagy is Regulated by mir-106b in the Heart
Authors: Kuhn Christian , Boeck Lisa , Hille Susanne , Dierck Franziska , Eschenhagen Thomas , Frey Norbert
Published: July 2021

Autophagy is a lysosome-dependent degradation mechanism. In the heart the autophagic flux is induced by starvation and by specific cardiac disorders ranging from pressure overload to myocardial infarction. Recently, microRNAs have been implicated in the control of cardiac autophagy.

We found a significant induction of miR-106b in the heart of mice that had been starved for 48h (1.6±0.2-fold, n=11, p<0.05). Moreover, miR-106b is upregulated in cardiac tissue of patients with dilated cardiomyopathy (14.4±4.4-fold, n=3, p<0.05). Interestingly, miR-106b is induced in failing hearts of MLP knockout mice (11.5±2.6 fold, n=5, p<0.05), an established DCM model, as well.

Using four different target predictions algorithms (DIANA microT v4.0, miRDB, microRNA.org, TargetScan) we reduced the number of potential targets of miR-106b. Among the genes we found Fyco1. Fyco1 is predominantly expressed in striated muscle and interacts with LC3, a key player in autophagy. We have shown before that Fyco1 is sufficient to induce autophagy in cardiomyocytes. Conversely, Fyco1 deficient mice are protected from increased autophagy by starvation or transverse aortic constriction, but suffer from contractile dysfunction after cardiac stress.

Using the mirSVR tool we identified two potential binding sites in the 3’-UTR of murine Fyco1. We inserted each of the predicted binding sites into a luciferase gene based reporter system. Overexpression of miR-106b with either one of the predicted binding sites caused a significant loss of luciferase activity compared to cells that overexpressed a control microRNA or carried a mutated binding site. Interestingly, a fragment that included both target sites reduced the luciferase activity to the same extent (-32%, p<0.001). Overexpression of miR-106b in neonatal rat cardiomyocytes (NRCM) caused a reduction of Fyco1 protein by 72%. Consistently, the overexpression of miR-106b in NRCM prevented the induction of autophagy measured by LC3-II levels after glucose deprivation for 24h.

Taken together our data identify a miR-106b/FYCO1-dependent pathway regulating autophagy in the heart. It will be interesting to see whether experimental manipulation of this axis may alter the progression of cardiomyopathy and heart failure.
Abstract 14056: Prognostic Impact of Rho-kinase Activity in Circulating Leukocytes of Patients with Vasospastic Angina
Authors: Nihei Taro , Takahashi Jun , Tsuburaya Ryuji , Hao Kiyotaka , Odaka Yuji , Nishimiya Kensuke , Matsumoto Yasuharu , Ito Kenta , Shimokawa Hiroaki
Published: July 2021

Background:
Rho-kinase plays a central role in the pathogenesis of coronary artery spasm. We have recently demonstrated that Rho-kinase activity in circulating leukocytes is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). However, its prognostic impact in VSA patients remains to be examined.

Methods:
We prospectively enrolled 174 consecutive VSA patients (M/F 116/58, 62±12 [SD] yrs) and 53 non-VSA patients (M/F 32/21, 62±15 yrs) and followed them for 14±9 months. At the enrollment, Rho-kinase activity in circulating leukocytes (the ratio of phosphorylated/total form of myosin binding subunit, a Rho-kinase substrate) was measured. The primary endpoint was major adverse cardiac events (MACE).

Results:
Baseline Rho-kinase activity was significantly higher in VSA than in non-VSA patients (1.20±0.33 vs. 1.07±0.21, P<0.01) and all VSA patients were treated with calcium channel blockers. During the follow-up period, MACE occurred in 9 VSA patients (5.2%) but none in non-VSA patients. Baseline Rho-kinase activity was significantly higher in VSA patients with MACE than in those without it (1.33±0.13 vs. 1.20±0.33, P<0.001). Importantly, when we divided VSA patients into 2 groups by a median value of baseline Rho-kinase activity, Kaplan-Meier survival analysis showed a significantly worse prognosis in VSA patients with high Rho-kinase activity (p-MBS/t-MBS ≥1.20) (
Figure
). Univariate linear regression models showed that there was no association between established prognostic factors of VSA (e.g. history of out-of-hospital cardiac arrest, current smoking, angina at rest, significant organic stenosis and β-blocker use) and baseline increased levels of Rho-kinase activity.

Conclusions:
These results indicate that increased Rho-kinase activity in circulating leukocytes may be a useful and independent biomarker for long-term prognosis of VSA patients.
Abstract 143: An Assessment of Who Dies After Cardiac Arrest in the Era of Therapeutic Hypothermia
Authors: Zanyk McLean Katherine , VanRaemdonck Julie , Capoccia Diane , Turkelson Carman , Devlin William , Swor Robert , Sawyer Kelly N
Published: July 2021

Introduction:
Much emphasis is placed on who survives after cardiac arrest and how to optimize “good” outcomes. Despite this stress on aggressive post-arrest care and early temperature management, many people still die after admission to the hospital, often with care being withdrawn. The purpose of this study was to assess how and when patients die after undergoing in-hospital post-arrest therapeutic hypothermia (TH).

Methods:
This was a retrospective chart review of adult patients suffering non-traumatic cardiac arrest who had post-arrest care, including TH, initiated between January 2010 and June 2013 in a large, community academic center. All patients followed the same treatment protocol, with TH induced as soon as possible after arrest, regardless of initial rhythm or arrest location. Demographics, Utstein characteristics, and post-arrest variables, including time to withdrawal of care were collected until death or hospital discharge as part of an on-going quality improvement database. Descriptive statistics and associations are presented.

Results:
During the study period, 139 patients were included and 92 (66.2%) died prior to discharge (mean age 61.9 (SD 16.31) years, 88 (63.3%) male). Few (12, 13.0%) of these had early termination of the TH protocol or died (8, 10.0%) while intubated. Overall, 72 (78.3%) patients had care withdrawn. The median time from return of spontaneous circulation (ROSC) to withdrawal of care was 96.6 hours (IQR 66.2, 164.1) and 18 (27.3%) patients had care withdrawn <72 hours from ROSC. All patients were referred to the Gift of Life service but only 9 (12.5%) contributed to organ donation. A minority of patients (20, 27.8%) received a formal palliative care consult. Factors associated with withdrawal of care included family wishes, older age, initial non-shockable arrest rhythm, and longer time from arrest to ROSC.

Conclusion:
More than 75% of this cohort had care withdrawn. Although the majority had care withdrawn more than 72 hours after ROSC, early withdrawal of care was not uncommon. Further study of this group of patients is needed to understand the relationships between pre-arrest predictors of poor prognosis, pre-existing co-morbidities, patient clinical status, and family wishes on the early withdraw of care.
Abstract 14646: Internal Medicine Housestaff Perceptions of Statins and ACC/AHA Blood Cholesterol Guidelines
Authors: Flueckiger Peter , Juraschek Stephen , Eades Micah , Khera Amit , Blaha Michael , Sperling Laurence
Published: July 2021

Background:
Statins are integral in the prevention of atherosclerotic cardiovascular disease (ASCVD). Provider perceptions and prescribing practices of statins vary. Internal medicine housestaff (HS) perceptions of statins and new ACC/AHA cholesterol guidelines have not previously been assessed.

Methods:
We examined internal medicine HS perceptions of statins and ACC/AHA cholesterol guidelines through a 48-question survey. We surveyed HS at three academic training programs. Anonymous responses were collected via a secure website.

Results:
99 respondents’ results (84% categorical residents) were examined from Emory, Johns Hopkins, and UTSW. HS report observing low rates of statin side effects: 64% and 91% reported rates of <3% and <10%. Majority of side effects were myalgias (69%), transaminitis (23%), and gastrointestinal symptoms (5%). Over half (54%) of respondents check transaminases prior to statin therapy. If transaminitis >1-2x upper limit of normal (ULN) develop only 6% of residents stop statin therapy, though 62% stop therapy if transaminitis >3x ULN. In stable liver disease, 13% use non-statin therapy. Most residents (73%) agree that patients understand why they are prescribed statins and feel compliance is influenced by experienced/perceived risk of side effects (44%), cost (30%), and medical benefit (13%). However, HS do not discuss side effects in 25% of patients and only 44% agree patients frequently ask about side effects. Additionally, only 51% of HS discuss ASCVD risk with a majority of patients. HS perceive high rates of statin adherence (87% state >50% adherence at one year).

Of 61 HS, 72% learned of new lipid guidelines through residency training. Nearly all (89%) read a portion of the guidelines and are likely to implement them (97%). However, only 57% agree the guidelines are clear or straightforward to apply in clinical practice and 66% agreed the guidelines will improve/reduce ASCVD risk. Only 48% agree new guidelines will improve quality of patient care.

Conclusion:
Practice patterns of statin therapy vary among medicine HS. Side effects and ASCVD risk are not frequently discussed with patients. Though HS are aware of new cholesterol guidelines, a gap exists between implementation and perceived benefits/ASCVD risk reduction.
Abstract 14650: A Monoclonal Antibody to a Sodium Pump Inhibitor Marinobufagenin Reversed Aortic Remodeling and Stiffness in Normotensive Rats on a High Salt Intake
Authors: Grigorova Yulia , Wei Wen , Zernetkina Valentina , Juhasz Ondrej , Lakatta Edward , Fedorova Olga , Bagrov Alexei
Published: July 2021

Background:
Marinobufagenin (MBG), an endogenous cardiotonic steroid, is a Na/K-ATPase inhibitor and a vasoconstrictor. Previously it was demonstrated, that administration of 3E9 anti-MBG-antibody (mAb) reduced blood pressure (BP) and reversed left ventricular fibrosis in animal models of salt-sensitive hypertension and nephropathy. In the present study we investigated whether mAb alleviates BP and vascular remodeling in normotensive rats on a high salt intake.

Methods:
Wistar rats (5 months old) received normal salt diet (CTRL; n=8) or high salt intake (2% NaCl in drinking water) for 4 weeks. Rats on a high salt were administered vehicle (SALT; n=8) or mAb (50 ug/kg) (SALT-AB; n=8) 3 times during the last week of a high salt diet. BP was measured at baseline, after 3 and 4 weeks of experiment. Na/K-ATPase activity was measured in erythrocytes. Aortas were weighed, and were used to study sensitivity to the vasorelaxant effect of sodium nitroprusside (SNP), and for the histochemistry analysis of collagen deposition. Renal 24-hr MBG excretion was measured at week 4.

Results:
In SALT vs. CTRL, in the absence of BP changes, elevated levels of MBG (14.1±1.1 vs. 9.0±1.6 pmol/24hr, p<0.05) were associated with inhibition of erythrocyte Na/K-ATPase (12.6±0.3 vs. 14.2±0.35 μmol Pi/ml/hr, p<0.05), increased aortic weights (217±15 vs. 158±9 mg/kg BW, p<0.01), increased levels of collagen in aorta (2.5-fold; p<0.05), and compromised SNP vasorelaxant effect in aortic explants (EC50=167±19.3 nM vs. 99±2.0 nM; P<0.01). Antibody treatment in SALT-AB vs. SALT increased Na/K-ATPase activity (13.93±0.54 μmol Pi/ml/hr, p<0.05), reduced the aortic weight (180±12 mg/kg; P<0.05) and collagen deposition 3-fold (P<0.05), and restored the vasorelaxation of aortic rings by SNP to the levels in CTRL (70±1.5 nM, p<0.01).

Conclusion:
These findings for the first time demonstrated that in normotensive rats on a high salt intake heightened MBG levels induced vascular fibrosis and impairment of vasorelaxation in the absence of blood pressure changes. Immunoneutralization of MBG reversed these changes. Thus, high dietary NaCl intake in normotensive animals can stimulate vascular fibrosis via pressure-independent/ MBG-dependent mechanisms, and this remodeling is reversible.
Abstract 14685: Efficacy of Combined Administration of Intracoronary Papaverine and Intravenous Adenosine 5’-Triphosphate in Assessment of Fractional Flow Reserve
Authors: Nishi Takeshi , Fujimoto Yoshihide , Kobayashi Yoshio
Published: July 2021

Purpose:
Inducing maximal coronary hyperemia is important to measure fractional flow reserve (FFR) accurately. Administration of intracoronary (IC) papaverine and intravenous (IV) adenosine 5’-triphosphate (ATP) have been used to achieve maximal hyperemia in the assessment of FFR. However, they may not induce maximal hyperemia in all patients. We aimed to evaluate combined effect of IC papaverine and IV ATP on FFR measurements.

Methods:
FFR measurements using administration of IC papaverine (12 mg in the left coronary artery and 8 mg in the right coronary artery), IV ATP (140 μg/kg/min), and the combination of IC papaverine plus IV ATP (additional IC bolus infusion of papaverine during IV ATP) were performed in 57 lesions of 52 consecutive patients. FFR values, symptoms, development of atrioventricular block (AVB), and ventricular arrhythmia were recorded.

Results:
Mean FFR values with IC papaverine, IV ATP, and the combination of IC papaverine and IV ATP were comparable (0.75 ± 0.13 vs. 0.76 ± 0.13 vs. 0.75 ± 0.13, p = 0.87). The proportion of lesions with a positive FFR (FFR ≤0.80) were not significantly different between the 3 methods (54.4% vs. 47.4% vs. 64.9%, p = 0.17). IC papaverine and IV ATP detected 25 lesions and 32 lesions with a negative FFR (FFR > 0.80), respectively. Of these, 7 (28%) and 11 lesions (34%) showed positive FFR with the combination of IC papaverine and IV ATP. Within the region of physiologically intermediate FFR values (0.75 to 0.85 obtained by IV ATP), there were significant differences in the FFR values (0.81 ± 0.02 vs. 0.79 ± 0.03, p = 0.01) and the proportion of positive FFR (48.3% vs. 66.7%, p < 0.01) between IV ATP and the combination of IC papaverine and IV ATP. IC papaverine increased ventricular premature contraction in 2%. IV ATP caused flushing in 48%, chest oppression in 27%, shortness of breath in 10%, and transient 2nd degree AVB in 3%. The combination of IC papaverine and IV ATP caused transient 2nd degree AVB in 2%.

Conclusions:
The hyperemic efficacy of IC papaverine or IV ATP alone is suboptimal in some patients. Combined administration of IC papaverine and IV ATP can achieve optimal hyperemia in such patients and has the potential to assist in making clinical decisions on patients with physiologically intermediate lesions.