bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 15110: Exercise Training for Management of Peripheral Arterial Disease: a Systematic Review and Meta-Analysis
Authors: Parmenter Belinda , Dieberg Gudrun , Smart Neil A
Published: July 2021

Objective:
To quantify expected benefits of exercise training in people with peripheral arterial disease (PAD).

Hypothesis:
Walking as a training modality and training to mild pain were optimal for improving peak VO
2
and symptoms.

Methods:
We conducted a systematic search (PubMed, CINAHL, Cochrane controlled trials registry; 1966-May 31, 2014).We included randomized controlled trials (RCT’s) of exercise training versus usual medical care in persons with PAD, 42 of 60 (70%) RCT’s met selection criteria.

Results:
Exercise training produced significant peak VO
2
improvements with Mean Difference (MD) 0.62 ml/kg/min (95% CI 0.47 to 0.77; p<0.00001); 6 minute walk initial claudication MD 52.7m (95%CI 24.7 to 80.6m; p=0.0002); total walking distance MD 34.9m (95%CI 25.6 to 44.1m; p<0.00001); graded treadmill initial claudication MD 68.8m (95%CI 54.4 to 83.2m; p<0.00001); absolute claudication distance MD 41.0m (95%CI 28.8 to 53.2m; p<0.00001)); but not ABI (p=0.12) or FMD (p=0.96). Sub-analyses of maximum change in Peak VO
2
showed arm cranking to be the superior modality MD 1.91 ml.kg
-1
.min
-1
(95% CI 1.28 to 2.54, p<0.00001). Sub-analysis of peak VO
2
according to pain thresholds suggested that exercise training with no or mild pain may be superior MD 0.79 ml.kg
-1
.min
-1
(95% CI 0.45 to 1.14, p<0.00001) to moderate/maximum pain MD 0.49 ml.kg
-1
.min
-1
(95% CI 0.31 to 0.66, p<0.00001). Exercise training significantly improved Walking Impairment Questionnaire (WIQ) speed [MD 9.90 (95% CI 7.10 to 12.71, p<0.00001)]; WIQ distance [MD 7.04 (95% CI 3.98 to 10.10, p<0.00001)] and WIQ stair climbing [MD 4.99 (95% CI 3.03 to 6.69, p<0.00001)]. Perceived symptoms were not improved. SF-36 physical score was significantly improved compared to control [MD 1.27 (95% CI 0.41 to 2.13, p=0.004)], but not SF-36 mental score.

Conclusions and Relevance:
Various modes of exercise improve cardio-respiratory fitness, pain free and total flat ground walking distances and graded treadmill performance in PAD. Alternative modes of exercise are understudied in terms of quality of life, however walking to some level of claudication pain improves WIQ speed, distance and stair climbing scores in PAD as well as SF-36 physical component score.
Abstract 15114: Paradoxical Association of Ventricular Tachyarrhythmias and All-Cause Mortality in Patients With Renal Impairment: a MADIT-CRT Substudy
Authors: Daimee Usama , Moss Arthur , Goldenberg Ilan , Ruwald Martin , Zareba Wojciech , Merkely Bela , McNitt Scott , Polonsky Bronislava , Kutyifa Valentina
Published: July 2021

Background:
The risk of ventricular tachyarrhythmias (VTAs) in mild heart failure patients with renal dysfunction receiving cardiac resynchronization therapy plus an implantable cardioverter-defibrillator (CRT-ICD) or an ICD alone is not well understood.

Hypothesis:
We assessed the hypothesis that baseline renal function affects risk of VTAs and all-cause mortality as well as benefit derived from CRT-ICD during in-trial follow-up.

Methods:
We evaluated the impact of renal function in 1274 patients with mild heart failure and left-bundle branch block enrolled in MADIT-CRT. Patients with BUN>70 mg/dl or creatinine>3.0 mg/dl were excluded from the trial. Two subgroups were created based on the estimated glomerular filtration rate (GFR): GFR<60 and GFR≥60 ml/min/1.73 m2. Patients were studied over 3.3 years of follow-up for endpoints of ventricular tachycardia ≥200 beats per minute or ventricular fibrillation (fast VT/VF) and all-cause mortality.

Results:
The 413 patients with GFR<60 ml/min/1.73 m2 (mean 48.1±8.3) experienced lower risk of fast VT/VF (HR: 0.63, 95% CI: 0.44-0.90, p=0.012) but increased risk of death (HR: 2.43, 95% CI: 1.67-3.57, p<0.001), relative to those in the GFR≥60 group (mean 79.6±16.0) [Figure]. For both, CRT-ICD relative to ICD-only treatment was associated with lower likelihood of fast VT/VF (GFR<60: HR=0.46, 95% CI: 0.24-0.86, p=0.016; GFR≥60: HR=0.54, 95% CI: 0.38-0.76, p<0.001) without a significant effect on death (GFR<60: HR=0.62, 95% CI: 0.38-1.04, p=0.065; GFR≥60: HR=0.78, 95% CI: 0.45-1.36, p=0.379). There was no significant treatment interaction for the endpoints (p>0.10).

Conclusion:
In conclusion, in mild heart failure patients, moderate renal dysfunction is associated with lower risk of VTAs but greater risk of all-cause mortality relative to mildly impaired-to-normal renal function. In both groups, similar benefit from CRT-ICD was found in reducing risk of VTAs.
Abstract 15178: Assessment of Optical Coherence Tomogaphic Findings between Cobalt-Chromium Everolimus-Eluting Stents and New Generation Drug-Eluting Stents
Authors: Ohtani Hirofumi
Published: July 2021

Introduction:
Uncovered and malapposed stent struts are risk of stent thrombosis in drug-eluting stents (DES). Second-generation DESs improved endothelial coverage and reduced stent thrombosis rate compared to those of first-generation DESs. However few studies have directly compared stent coverage using OCT between second-generation DESs (CoCr-EES or R-ZES) and new generation drug-eluting stents (platinum-chromium EES; PtCr-EES). The aim of this study is to compare OCT findings between CoCr-EES, R-ZES and PtCr-EES at 9 months after stent implantation.

Methods:
Total of 30 patients who underwent single stent implantation in de novo coronary arteries leasions without target lesion revascularization were included (10 CoCr-EESs, 10 PtCr-EESs and 10 R-ZESs). Cross-sectional OCT images were analyzed at 1-mm intervals. At every cross-section (CS), stent area and neointimal hyperplasia area (NIA) were measured and percent NIA [(NIA /stent area)[[Unable to Display Character: ☓]]100] were calculated. For each strut, neointimal thickness (NIT), malapposed and uncovered struts were assessed. Strut malapposition was defined as detachment from the vesell wall by >90μm for CoCr-EES, by >100μm for R-ZES, or by >90μm for PtCr-EES.

Results:
Total of 4646 struts and 588 CS were analyzed. Baseline patient and lesion characteristics were similar between 3 groups. In CoCr-EESs, NIT was thinner than the others (CoCr-EES: 70μm (30-130μm) vs. R-ZES: 80μm (40-150μm) vs. PtCr-EES: 90μm (50-140μm); p=0.0001). The percent NIA were similar among the groups (R-ZES: 8.1% vs. CoCr-EESs: 8.4% vs. PtCr-EES: 10%; p=0.18). PtCr-EESs had less frequency of malapposed (PtCr-EES: 0.08% vs. CoCr-EES: 0.4% vs. R-ZES: 0.9%, p=0.005) and uncovered (PtCr-EES: 0.94% vs. R-ZES: 2.2% vs. CoCr-EES: 3.4%; p=0.0001) struts than the others.

Conclusions:
PtCr-EESs had fewer uncovered struts and better stent apposition although greater NIT than CoCr-EESs and R-ZESs. These findings may suggest the fewer risks for stent thrombosis in PtCr-EESs.
Abstract 15193: The Impact of Age and Gender on Door to Balloon Time in Patients with ST Elevation Myocardial Infarction
Authors: Nagumo Sakura
Published: July 2021

Introduction:
Shortening door-to-balloon (D2B) time is important to improve outcomes in patients suffering ST elevated acute myocardial infarction (STEMI). Age and gender are associated with poor outcomes in previous reports, however the impact of differences in age and gender on D2B time is still unclear.

Objective:
To determine the association of age and gender with D2B time in patients suffering STEMI.

Methods:
The Yokohama cardiovascular workshop registry is a prospective multicenter cohort in an urban area of Japan. 1261 consecutive STEMI patients during May 2010 to May 2013 were enrolled for the present analysis. Patients were divided into four groups according to age (>75years old) and gender; elderly female (n=146), young female (n=125), elderly male (n=206) and young male (n=783).

Results:
D2B time was longer in female gender (93.2 vs. 85.5 min, p<0.01) and in the elderly (92.3 vs. 85.1, p<0.001). Among the four groups described above, D2B time was the longest in elderly female patients and followed by young female patients (p=0.002). Elderly female patients also had the lowest proportion of Killip class I, the longest time interval from hospital arrival to achieve TIMI flow grade 2/3, the worst final TIMI flow grade and the highest in-hospital mortality. The percentage of patients in achieving D2B time <90min was the lowest in elderly male (p<0.001, odds ratio 0.54) followed by elderly female (p=0.009, odds ratio 0.61).

Conclusions:
Both female gender and higher age were associated with longer D2B time in patients with STEMI. Further effort should be made to shorten the D2B time, especially in the elderly and women, for the improvement of clinical outcomes.
Abstract 15293: Increased Level of Cardiac Troponin T is a Clue of Cardiac Amyloidosis in Patients With Myocardial Hypertrophy
Authors: Takashio Seiji , Yamamuro Megumi , Anzai Toshihisa , Ogawa Hisao
Published: July 2021

Background:
Cardiac amyloidosis (CA) is an important differential diagnosis in patients with myocardial hypertrophy. The precise diagnosis of CA requires endomyocardial biopsy to demonstrate amyloid deposition, but this procedure is relatively invasive and cannot be performed routinely. Therefore, it is important to increase pretest probability of CA in patients with myocardial hypertrophy by noninvasive modalities. Because it is well known that cardiac troponin level is elevated in patients with CA, we hypothesized that increased level of cardiac troponin T contributes to diagnosis of CA in patients with myocardial hypertrophy using high sensitive assay (hs-TnT).

Methods and Results:
Among nonischemic patients with myocardial hypertrophy (interventricular septal thickness≧ 12 mm), hs-TnT level was measured in 28 CA patients (senile systemic amyloidosis: 13, AL amyloidosis: 14, familial amyloidosis: 1) proven amyloidosis pathologically and 29 non-CA patients proven by endomyocardial biopsy. It was significantly higher in CA patients than non-CA patients (0.075 [0.047-0.116] ng/ml vs. 0.013 [0.009-0.019] ng/ml; p<0.001: Figure). Receiver operating characteristic analysis selected 0.030 ng/ml as the best cutoff value of diagnosis for CA, with a sensitivity and specificity of 96% and 93%, respectively and area under the curve of 0.98 (95% confidence interval 0.94 to 1.00, p<0.001).

Conclusions:
Increased level of hs-TnT (>0.030 ng/ml) is highly suggestive of CA in patients with myocardial hypertrophy. These patients need additional diagnostic approach for CA.
Abstract 15295: Molecular Mechanism of Chronic Sildenafil-Caused Regression of Heart Failure: Effects on the Express of Cardiac SR Ca2+-ATPase, Subtype of β-Adrenergic Receptors and Nitric Oxide Synthase Isoforms
Authors: Cheng Heng-Jie , Li Tiankai , Cheng Che Ping
Published: July 2021

Background:
Sildenafil (SIL), a selective inhibitor of PDE5 has been shown to exert profound beneficial effects in heart failure (HF). Recently we further found that SIL caused regression of cardiac dysfunction in a rat model with isoproterenol (ISO)-induced progressive HF. However, the molecular basis is unclear. We hypothesized that reversal of HF-induced detrimental alterations on the expressions of cardiac SR Ca
2+
-ATPase (SERCA2a), β-adrenergic receptors (AR) and nitric oxide synthase (NOS) isoforms by SIL may play a key role for its salutary role in HF.

Methods:
Left ventricular (LV) and myocyte function and the protein levels of myocyte β
1
- and β
3
- AR, SERCA2a, phospholamban (PLB) and three NOS were simultaneously evaluated in 3 groups of male rats (6/group):
HF
, 3 months (M) after receiving ISO (170 mg/kg sq for 2 days);
HF/SIL
, 2 M after receiving ISO, SIL (70 μg/kg/day sq via mini pump) was initiated and given for 1 M; and
Controls
(C).

Results:
Compared with controls, ISO-treated rats progressed to severe HF at 3 M after ISO followed by significantly decreased LV contractility (E
ES
, HF: 0.7 vs C: 1.2 mmHg/μl) and slowed LV relaxation, reductions in the peak velocity of myocyte shortening (77 vs 136 μm/sec), relengthening (62 vs 104 μm/sec) and [Ca
2+
]
iT
(0.15 vs 0.24) accompanied by a diminished myocyte inotropic response to β-AR agonist, ISO (10
-8
M). These abnormalities were associated with concomitant significant decreases in myocyte protein levels of β
1
-AR (0.23 vs 0.64), SERCA2a (0.46 vs 0.80), PLB
Ser16
/PLB ratio (0.24 vs 0.40) and eNOS (0.28 vs 0.46), but significantly increases in protein levels of β
3
-AR (0.29 vs 0.10) and iNOS (0.18 vs 0.08) with relatively unchanged nNOS. Chronic SIL prevented the HF-induced decreases in LV and myocyte contraction, relaxation, peak [Ca
2+
]
iT
,

and restored normal myocyte contractile response to ISO stimulation. With SIL, protein levels of myocyte β
1
- and β
3
-AR, SERCA2a were restored close to control values, but eNOS was significantly elevated than controls (0.77).

Conclusions:
Chronic SIL prevents HF-caused downregulation of cardiac β
1
-AR and reverse contrast changes between iNOS and β
3
-AR with SERCA 2a and eNOS expression, leading to the preservation of LV and myocyte function, [Ca
2+
]
iT
, and β-adrenergic reserve.
Abstract 15297: A Bundled Approach to Improving Code Team Response for In-hospital Cardiac Arrest to Decrease Overcrowding and Improve Role Clarity and Leadership
Authors: Leary Marion , Holena Daniel N , Neefe Stacie , Davis Leah , Tsypenyuk Boris , Falk Scott A , Schweickert William
Published: July 2021

Background:
Little is known about how non-technical factors such as inadequate role definition and overcrowding may impact in-hospital cardiac arrest (IHCA) outcomes. Using a bundled intervention, we sought to decrease overcrowding while improving provider role ambiguity and leadership at IHCA events.

Objective:
To examine interventions targeted at decreasing overcrowding, improving role ambiguity and leadership during IHCA.

Methods:
As part of a performance improvement initiative, a multidisciplinary team implemented four countermeasures to improve IHCA code response: an MD/RN leadership dyad, assigned optimal team composition, scripted role definitions, and visual (stickers)/verbal (role-checks) cues.

Between 4/2013-4/2014, the number and discipline of providers responding to ICHA events were recorded at each pulse check, and a 10-point Likert scale survey assessing communication and leadership was performed pre- and post-intervention. The primary outcome was the number of providers present after the role checks. Secondary outcome examined communication and leadership performance. Mann-Whitney test was used for continuous variables and chi-squared or Fischer’s exact test was used to compare categorical variables.

Results:
20 pre-intervention and 34 post-intervention IHCA events were captured. During both periods, MDs and RNs comprised the majority of the total providers present (61%, 57%). The median number of MDs present in the post-intervention group was lower than in the pre-intervention group (4 (IQR 4-5) vs. 7 (IQR 5-9), p= 0.004), as was the number of total overall providers (14 (IQR 12-16) vs. 18 (IQR 14-22), p=0.04). The number of RNs did not differ post-intervention (data not shown).

Survey results showed no significant differences in perceptions of communications or physician leadership post-intervention. However, the overwhelming majority of both the MD code leaders (90%) and primary nurses (97%) identified that there was a clear RN leader and rated the leadership provided by RN lead consistently high with a median score of 9 out of 10 possible points.

Conclusions:
Using an innovative bundle can decrease overcrowding and improve role ambiguity and leadership during non-ICU IHCA events.
Abstract 15314: Differential Association of Polymorphic Genetic Variants With Non-Pulmonary Vein Triggers in Patients With Non-Paroxysmal Atrial Fibrillation: Results From a Prospective Study (DECAF)
Authors: Mohanty Sanghamitra , Hall Amelia W , Mohanty Prasant , Trivedi Chintan , Di Biase Luigi , Bai Rong , Al-Ahmad Amin , Horton Rodney , Burkhardt John D , Sanchez Javier , Zagrodzky Jason , Bailey Shane , Gallinghouse Joseph G , Hranitzky Patrick , Iyer Vishwanath R , Natale Andrea
Published: July 2021

Introduction:
Earlier evidences support the origin of ectopic beats from non-pulmonary vein (non-PV) areas that initiate and maintain AF and elimination of these triggers is known to provide better arrhythmia-free survival. Of the different types, non-paroxysmal AF (NPAF) are more prevalently associated with non-PV drivers. Although emerging data on myocytes-fibroblast interactions provide some insight into the pathophysiology of non-PV triggers, the exact mechanism of origin of these ectopic foci is still unknown. Therefore, we examined the association of several AF-specific genetic variants with prevalence of non-PV triggers in NPAF patients undergoing catheter ablation.

Methods:
Four hundred AF patients (67% male, 62±12 year, left atrial size 45.3±7 mm, 64% non-paroxysmal) undergoing catheter ablation were prospectively enrolled at our center. DNA extraction and genotyping for 16 AF-associated SNPS from collected blood samples were performed using Qiagen QiaAMP 96 well blood kit and TaqMan assay respectively. Three hundred seventy-two DNA samples were available for genotyping. Multivariate logistic regression analysis (adjusted covariates: age, gender, LA size, hypertension and diabetes) was used for assessing predictive role of individual SNP; and logistic kernel-machine approach was applied to test the cumulative effect of multiple SNPs as a group with non-PV triggers.

Result:
In the non-paroxysmal AF population, significant allelic association was detected between non-PV triggers and rs6599230 (OR 0.57 [95% CI 0.31-0.88], p=0.042) and rs1448817 (OR 1.82 [95%CI 1.12-3.40], p=0.034). Interestingly, rs6599230 suggested a protective effect with 43% risk reduction while rs1448817 was an independent predictor of higher risk of developing non-PV triggers.

Conclusion:
Our results identified predictive association of two genetic variants, rs6599230 and rs1448817, with non-PV triggers in non-paroxysmal AF patients. Interestingly, the association was distinctive. The SNP, rs6599230 located in close proximity to SCN5A gene, was found to have a protective effect against development of arrhythmogenic triggers in the extra-PV sites whereas rs1448817 on chromosome 4q25 increased the risks of having non-PV triggers.
Abstract 15328: Benefits of Prophylactic Pulmonary Vein Isolation in Reducing Future Risk of Atrial Fibrillation in Patients Undergoing Catheter Ablation for Typical Atrial Flutter: Results From a Randomized Trial (REDUCE AF)
Authors: Mohanty Sanghamitra , Mohanty Prasant , Di Biase Luigi , Trivedi Chintan , Santangeli Pasquale , Bai Rong , Burkhardt John D , Gallinghouse Joseph , Horton Rodney , Sanchez Javier , Hranitzky Patrick , Al-Ahmad Amin , Hao Steven , Hongo Richard , Beheiry Salwa , Pellargonio Gemma , Forleo Giovanni , Rossillo Antonio , Themistoklakis Sakis , Casella Michela , Dello Russo Antonio , Tondo Claudio , Natale Andrea , Dixit Sanjay
Published: July 2021

Introduction:
Catheter ablation of cavo-tricuspid isthmus (CTI) is considered to be the most effective therapy for eliminating target arrhythmia in lone atrial flutter (AFL). However, many patients subsequently develop AF after CTI ablation. Therefore, prophylactic pulmonary vein antrum isolation (PVAI) along with CTI ablation could be considered as an alternate option in these patients. We aimed to compare long-term incidence of post-ablation atrial fibrillation following CTI alone or CTI plus PVAI in patients presenting with isolated AFL and no history of atrial fibrillation.

Methods:
This multi-center prospective randomized study enrolled 216 patients undergoing catheter ablation for isolated typical atrial flutter. Patients were randomized to CTI alone (group 1, n=108, 61.2±9.7 year, 75% male, LVEF 59±10%) or combined ablation CTI+PVAI (group 2, n=108, 62.4±9.3 year, 73% male, LVEF 57±11%). Insertible Loop Recorder (ILR) was implanted in 21 and 19 patients from group 1 and 2 respectively, on the day of the ablation procedure. Remaining patients were monitored for recurrence with event recorders, ECG, 7-day Holter and cardiology evaluation. All patients were followed up for 18±6 months for recurrence.

Results:
Compared to group 1, group 2 had significantly longer average procedural duration (75.9±33 min vs. 161±48 min [p <0.001]) and fluoroscopy time (15.9±12.3 min vs 56.4+21 min [p<0.001]). At the end of 18±6 months follow-up, 65 (60.2%) in group 1 and 77 (71.3%) in group 2 were arrhythmia free off-AAD (log-rank p=0.044). A subgroup analysis was performed with a 55 year age cut-off. In the <55 age group the CTI only population had similar success as in CTI+PVI without undergoing the additional PVI (21 of 24 [83.3%] vs. 19 of 22 [86.4%] respectively, log-rank p=0.74). In the ≥55 group, having CTI+PVI showed significantly higher success compared to CTI only; 45 of 84 (53.6%) were AF/AT free in CTI only group compared to 58 of 86 (67.4%) with CTI+PVI (log-rank p= 0.029). Distribution of AF incidence was not different between patients with and without ILR.

Conclusion:
Prophylactic PVAI in lone atrial flutter caused marked reduction in new-onset AF in patients ≥ 55 years whereas younger patients (<55 years) did not incur any benefit from the additional procedure.
Abstract 15365: Sleep-Disordered Breathing is Associated with Subclinical Myocardial Injury and Disease Severity in Pulmonary Hypertension Patients
Authors: Kohno Takashi , Tamura Yuichi , Kawakami Takashi , Kataoka Masaharu , Maekawa Yuichiro , Sano Motoaki , Fukuda Keiichi
Published: July 2021

Background:
Sleep disordered breathing (SDB) is well known to be associated with increased mortality in patients with left-heart failure, however the clinical significance of SDB in patients with pulmonary hypertension (PH) is not established. We sought to investigate the association of SDB with hemodynamic parameters and serum troponin T concentrations in patients with PH.

Methods and Results:
Overnight polygraphy was performed in 107 clinically stable patients with PH (pulmonary arterial hypertension n=52 [idiopathic n=23, collagen disease n=11, congenital heart disease n=6, others n=12]and chronic thromboembolic PH n=55), and evaluated apnea-hypopnea index (AHI; 7.6±9.3, obstructive apnea 1.8, central apnea 0.4, and hypopnea 5.3 events/h). Based on AHI, these patients were divided into two groups: non SDB (AHI<15/h, n = 90) and SDB groups (AHI≧15/h, n = 17). The presence of SDB was associated with older age (p<0.05), but not associated with gender, BMI, smoking, and the presence of hypertension, dyslipidemia, and diabetes mellitus. Hemodynamic studies showed that SDB patients had higher mean pulmonary artery pressure (mPA; 38±13 vs. 31±12 mmHg, p<0.05), higher pulmonary vascular resistance (PVR; 9.4±7.5 vs. 5.2±3.6 Wood, p<0.05) and lower cardiac output (3.4±0.9 vs. 4.8±1.9 L/min, p<0.05), but PCWP did not differ between two groups. In laboratory study, plasma BNP and serum CRP levels were not associated with SDB. However, high-sensitivity troponin T (hsTnT) level was significantly higher in patients with SDB than those without (0.017±0.014 vs. 0.008±0.006 ng/mL; p<0.05). HsTnT level positively correlated with plasma BNP level, mPA, PVR, and WHO functional class, and negatively correlated with cardiac output and 6 minute-walking distance (all p<0.05). Furthermore, after adjustment for age, lower eGFR, hypertension, smoking, and plasma BNP level in multiple regression analysis, the presence of SDB was the independent factor to determine plasma level of log hsTnT (β = 0.19, p<0.05).

Conclusions:
SDB is associated with subclinical myocardial damage and disease severity in patients with PH, suggesting the role of SDB-related myocardial injury in the vicious circle leading to hemodynamics destabilization and adverse prognosis.
Abstract 15371: Parathyroid Hormone-Related Peptide Protects Cardiomyocytes from Oxidative Stress: First Evidence of a Novel Endocrine-Cardiovascular Interaction
Authors: Chukkapalli Sahiti , Zhan Enbo , Lasley Robert , Datta Nabanita S
Published: July 2021

There is growing interest in the molecular cross-talk between the endocrine and cardiovascular systems, including the effects of hormones on cardiomyocte viability in models of ischemic and oxidative stress. However, current attention has focused on reproductive and metabolic hormones; the cardiac effects of calcium-regulating hormones (i.e., parathyroid hormone-related peptide (PTHrP)) have not been explored. To address this, we interrogated the effect of PTHrP on the viability of isolated adult mouse cardiomyocytes subjected to H
2
O
2
-induced oxidative stress. In
Aim 1
, myocytes from wild type (WT) C57 mice were incubated for 16 hrs with 100 nM PTHrP or vehicle and exposed to 100 μM H
2
O
2
for 15 min. Myocyte viability was significantly improved in PTHrP-treated cells
vs
vehicle control (70±12%
vs
20±15%; mean ± SD, p<0.01; Figure). Calcium sensing receptor and PTHrP signaling is purportedly associated with Mitogen-Activated Protein Kinases (MAPKs) and MAPK phosphatase-1 (MKP1). Accordingly, to achieve preliminary mechanistic insight into PTHrP-induced protection (
Aim 2
), we: (i) incubated WT cardiomyocytes with PTHrP (100 nM) and probed for expression of MKP1; and (ii) repeated the viability assay as described above using myocytes from adult MKP1 knockout (KO) mice. Incubation of WT myocytes with PTHrP evoked a 55% decrease in MKP1 expression. Moreover, myocytes from MKP1 KO mice were resistant to oxidative injury: viability was maintained at 78±12% in vehicle controls (mean ± SD, p<0.01
vs
the value of 20±15% in vehicle-treated WT cells), with no added benefit of PTHrP treatment (Figure). Finally (
Aim 3
), in both models (PTHrP treatment; MKP1 KO), the enhanced cell viability was accompanied by ~2-fold increases in Akt phosphorylation. These data provide novel evidence that: i) down-regulation of MKP1 affords profound protection against oxidative stress; and ii) PTHrP is cardioprotective, possibly via down-regulation of MKP1 and activation of Akt signaling.
Abstract 15404: Efficient and Persistent Transgene Expression by Minicircle Plasmid versus Standard Plasmid Using Ultrasound Targeted Microbubble Destruction
Authors: Rudenko Dmitriy , Matkar Pratiek N , Alghadeer Saleh A , Liao Christine , Chen Hao H , Kuliszewski Michael A , Leong-Poi Howard
Published: July 2021

Background:
Ultrasound-targeted microbubble destruction (UTMD) is a non-invasive gene transfection technique using carrier microbubbles and targeted high power ultrasound, primarily used to deliver plasmid DNA (pDNA). Minicircle-DNA (mcDNA) is a novel gene vector, which has recently been shown to have an improved and persistent transfection, compared to conventional pDNA.

Hypothesis:
We hypothesized that UTMD of mcDNA in a hind-limb model would exhibit a more potent and prolonged gene expression compared to conventional pDNA.

Methods:
In vitro
, HUVECs, fibroblasts (3T3) and neonatal cardiomyocytes were transfected with molar equivalents of GFP-minicircle and GFP-plasmid. GFP expression was measured by RT-PCR and fluorescent microscopy for 28 days. We then performed a comparison of bubble binding capacities of both vectors to cationic lipid microbubbles.
In vivo
, for UTMD to the left proximal hind-limb adductor muscle, 500μg and 214μg of GFP-plasmid and GFP-minicircle respectively were charge-coupled with 1x10
9
cationic microbubbles and delivered via UMGD into Sprague-Dawley rats (n=30). The animals were followed for 28 days with GFP measured by RT-PCR and immunohistochemistry.

Results:
In vitro
results showed greater GFP expression by mcDNA across all cell lines, with 7-10 fold transfection efficacy compared to pDNA. mcDNA demonstrated greater binding capacity to cationic microbubbles compared to pDNA. For plasmid and minicircle DNA, binding saturations were reached at ~6000 copies per microbubble, and ~20000 copies per microbubble respectively, suggesting a higher minicircle bubble binding efficiency.
In vivo
results showed higher GFP levels as early as 6 hours post minicircle UTMD, demonstrating minicircle to be a faster acting therapeutic agent over conventional plasmid. A significantly greater (p<0.01) expression of GFP was also evident at day 28 in minicircle UTMD-treated group, proving mcDNA to be a better choice for longer-term gene expression.

Conclusions:
In summary, UTMD using mcDNA results in more rapid and sustained transfection compared to conventional pDNA, and may be a more effective vector for translational studies of UTMD.
Abstract 15456: Enhanced Vasoconstrictor Sensitivity to Exercise Pressor Reflex Engagement in Peripheral Artery Disease
Authors: Gao Zhaohui , Muller Matthew D , Blaha Cheryl , Cauffman Aimee , Brandt Kristen , Reed Amy B , Sinoway Lawrence I , Leuenberger Urs A
Published: July 2021

Exercise is associated with a rise in heart rate, blood pressure (BP) and blood flow to active skeletal muscle that is mediated by the exercise pressor reflex and modified by regional release of vasodilator factors. In peripheral artery disease (PAD) the exercise pressor reflex is enhanced and the ability to raise blood flow to the affected limb is impaired. To assess the functional impact of the enhanced exercise pressor reflex on regional blood flow in limbs affected by PAD, we determined beat-by-beat BP and mean blood velocity (MBV, Doppler) in the popliteal artery, and calculated vascular conductance index (VC, MBV/mean BP) in the exercising (ipsilateral) or contralateral resting leg during graded rhythmic plantar flexion exercise in 7 patients with symptomatic PAD (age 67±2 yrs, body-mass-index 27.9±1.1) and in 5 healthy age-matched controls (2 exercise trials with each leg). At peak exercise (2.0 kg, 1 contraction/sec), the pressor effect was greatest in PAD when exercise was performed with the “ischemic” leg (ankle-brachial index 0.58±0.05; mean ΔBP +9.1±2.0 mmHg), lower with the less affected leg (ankle brachial index 0.76±0.07; mean ΔBP +6.9±1.6 mmHg) and lowest in the controls (ankle brachial index 1.11±0.04; mean ΔBP +3.9±1.8 mmHg). In controls, VC increased in the exercising leg (
P
<0.05) but did not change in the inactive contralateral leg (
P
=NS). Similarly, in PAD, VC increased in the exercising “ischemic” leg (
P
<0.05) but did not change in the inactive contralateral leg (
P
=NS). In sharp contrast, while VC increased in the less affected exercising leg (
P
<0.05), in the contralateral resting “ischemic” leg VC decreased by 24±10% (
P
<0.05). Similarly, when static handgrip at 30% maximum voluntary contraction to fatigue served as the exercise stimulus, vasoconstriction was noted in the “ischemic” leg (n=5;
P
<0.05). Thus, unlike in the exercising leg, in the resting “ischemic” leg activation of the exercise pressor reflex resulted in substantial vasoconstriction. This suggests that despite activation of peripheral vasodilator mechanisms downstream to the arterial obstruction, the vasculature of the “ischemic” leg is exquisitely sensitive to reflex vasoconstriction.
Abstract 15504: A New Coronary Anastomotic Connector in a Preclinical Safety Study
Authors: Stecher David , Pasterkamp Gerard , Buijsrogge Marc P
Published: July 2021

Introduction:
A facilitated construction of a distal coronary anastomosis is the key towards less invasive coronary bypass surgery, ideally in an endoscopic hybrid approach. This study evaluates a new laser-assisted, zero ischemia coronary anastomotic connector in comparison to the hand-sutured anastomotic technique, in a long-term follow-up porcine off-pump bypass model. The initial results of this preclinical comparative safety study are presented.

Hypothesis:
We assessed the hypothesis that the coronary connector is not inferior to the hand-sutured technique, in terms of patency, healing, and hemodynamic function.

Methods:
In 22 pigs (3 months follow-up, n=10; 6 months follow-up, n=12), the so-called Trinity Clip connector facilitated a LITA-to-LAD anastomosis, and in 14 pigs (3 months follow-up, n=6; 6 months follow-up, n=8) the anastomosis was hand-sutured. All anastomoses (n=36) were evaluated intraoperatively by means of graft flow measurements and at follow-up by angiography and histology.

Results:
After construction, complete hemostasis was obtained in 95% (21/22) of the connector facilitated anastomoses and in 86% (12/14) of the hand-sutured. Both groups had a mean coronary outer diameter of 1.8 ± 0.1 mm. The mean peak hyperemic flow response (peak [following 30-second graft occlusion]/base flow) was 4.1 ± 1.0 in the connector group versus 4.2 ± 1.1 in the hand-sutured group. The patency in both groups was 100% (connector group: at 6 months [n=3/3] and 3 months [n=5/5]; hand-sutured group: at 6 months [n=1/1] and 3 months [n=4/4]).

Conclusions:
The initial data of this preclinical study demonstrates similar anastomosis success rate in both groups. The connector is easy-to-use and seems to be safe and reliable in the long-term porcine off-pump bypass model. Complete data on the long-term will be expected soon and the resulting histological and angiographic data will further elucidate the future relevance of this new coronary anastomotic device. In conclusion, albeit the preliminary study status, the connector has potential to facilitate minimally invasive or endoscopic CABG.
Abstract 15541: Effect of Stress Perfusion and Wall Motion Response on Outcome of Obese versus Non-Obese Subjects Without Known Coronary Artery Disease
Authors: Nicola Gaibazzi , Lorenzoni Valentina , Reverberi Claudio , Wu Juefei , Xie Feng , Porter Thomas R
Published: July 2021

Background:
Although several studies have demonstrated a protective effect of obesity in coronary artery disease (CAD), it is unclear whether this protective effect is evident in patients referred for stress imaging. Real time contrast echocardiography (RTCE) permits the simultaneous analysis of perfusion and wall motion during different forms of stress echocardiography.The objective of this study was to determine whether a protective effect of obesity is evident in subjects referred for pharmacologic stress RTCE.

Methods and Results:
Wall motion (WM) and myocardial perfusion (MP) with RTCE (using SonoVue and Definity ultrasound contrast) were assessed in 2106 consecutive patients without known CAD referred for either dobutamine (n=1209) or dipyridamole (n=897) stress echocardiography. Of these, 481 (23%) were obese (body mass index>30 kg/m2). Outcome (death/non-fatal infarction) was determined over a median follow-up of 1022 days. Multivariate Cox Models were created from significant univariate variables to assess hazard ratios (HR) and 95% confidence intervals (CI). Abnormal MP and/ or WM were seen in 246 dobutamine and 169 dipyridamole studies (equally distributed between obese and non-obese). Although event free survival (EFS) was significantly better for obese versus non-obese subjects with normal tests (p=0.01) and in obese patients with abnormal dobutamine stress perfusion/wall motion responses (p=0.009), obesity was not an independent clinical predictor of outcome, while age (HR 1.04 (95% CI 1.03-1.06) and male gender (HR 2.26;(95% CI 1.59-3.21) did independently predict outcome (both p<0.001). Furthermore, abnormal responses to stress (either dobutamine or dipyridamole) were associated with significantly worse prognosis, independent of age, gender, or obesity (HR 2.67;95% CI 1.91-3.77).

Conclusions:
Although obese subjects with both normal and abnormal responses to pharmacologic stress have improved EFS when compared to non-obese with the same test result, this trait is not independently associated with outcome. Perfusion and wall motion responses determined with RTCE add significant predictive value in this setting irrespective of age, gender, or obesity status.
Abstract 15562: Impact of Off-time Presentation on the Vulnerability of the Culprit Lesions in ST-elevation Acute Myocardial Infarction
Authors: Kim Young , Kim Sang Wook , Lee Wang Soo , Won Hoyoun , Hyeon Seong Hyeop , Kwon Jee Eun , Chung Yoon Sang , Shin Seung Yong , Lee Kwang Je , Kim Tae Ho , Kim Chee Jeong
Published: July 2021

Background:
ST-elevation myocardial infarction (STEMI) that occurs during the off hours shows worse clinical status compared to the patients presenting during working hours.

Method:
We used Virtual Histology Intravascular Ultrasound (VH-IVUS) to assess the complexity of culprit lesion in 193 patients with STEMI. The patients were divided into two groups that presented to the hospital during the working hours (from 8:30 am to 6:00 pm) and the off hours (from 6:00 pm to 8:30 am of the next day). VH-TCFA (thin-capped fibroatheroma) was defined as necrotic core (NC) >10% of plaque area with a plaque burden of >40% and NC in contact with the lumen for ≥3 image slices. Positive remodeling was a remodeling index (lesion/reference EEM [external elastic membrane] area) >1.05.

Result:
91(46.0%) pts were visited during working hours, and 102(54.0%) pts during the off hours. Pt age was 60±13 yr in working hour STEMI and off hour STEMI was 61±10 yr. The lesion length, vessel size and minimal lumen area (MLA) were similar. The average and maximum necrotic core area of the off hours STEMI were larger than the working hours STEMI(p=0.025 and p=0.005 respectively). The remodeling index at maximum necrotic core site was also higher in the off hours STEMI than the working hours group respectively (p=0.042). Positive remodeling was 42.9%(39/91) in working hour STEMI and 59.8%(61/102) in off hour STEMI (p=0.028). However, the frequency of TCFA was similar in both group(25.7% vs 26.6%, p=0.123).

Conclusion:
The culprit lesions of Off-hour STEMI may more vulnerable compared to STEMI occuring during the working hours.
Abstract 15563: Neurovascular Control and Spontaneous Baroreflex Sensitivity in Heart Failure Patients with Preserved Ejection Fraction
Authors: Sayegh Ana Luiza C , dos Santos Marcelo R , de Souza Francis R , Salemi Vera Maria C , Oliveira Carlos Augusto P , Fonseca Felipe X , Rodrigues Sara , Trombetta Ivani C , Toschi-Dias Edgar , Negrão Carlos Eduardo , Alves Maria-Janieire N , Mady Charles
Published: July 2021

Introduction:
Muscle sympathetic nerve activity (MSNA) and forearm blood flow (FBF) are markers of mortality in Systolic Heart Failure (S-HF). Endomyocardial Fibrosis (EMF) is a Heart Failure (HF) with Preserved Ejection Fraction (PEF-HF). Although mortality in PEF-HF can be similar to S-HF, it is still unknown if neurovascular control is impaired in PEF-HF.

Hypothesis:
Our hypothesis is that even though PEF-HF show normal ejection fraction, they have the same autonomic dysfunction as S-HF. The aim was to evaluate MSNA, FBF and spontaneous baroreflex sensitivity (SBS) in PEF-HF compared to S-HF and healthy subjects (HS).

Methods:
Nineteen females HF, NYHA class II and III, were divided in two groups: PEF-HF (n=10) and S-HF (n=9), and were compared to HS (n=7). Left Ventricular Ejection Fraction (LVEF), by echocardiography (Simpson); MSNA, by microneurography; FBF, by venous occlusion plethysmography; mean blood pressure (MBP) and heart rate (HR) by Finometer; SBS, by sequence method, were measured. Significance was considered p<0.05.

Results:
Age was not different between PEF-HF, S-HF and HS (57±2 vs. 55±2 vs. 52±1 years; p<0.15, respectively). LVEF was higher in PEF-HF and HS compared to S-HF (55±3 vs. 65±1 vs. 33±2%; p<0.02, respectively). MSNA in bursts per minute (35±3 vs. 40±2 vs. 20±1 bursts/min; p<0.001) and MSNA per 100 heart beats (50±4 vs. 57±3 vs. 26±2 bursts/100 HB; p<0.001) were higher in PEF-HF and S-HF compared to HS, respectively. FBF was lower in PEF-HF and S-HF compared to HS (1.45±0.2 vs. 1.78±0.3 vs. 2.70±0.3 ml/min/100ml; p<0.047). Forearm vascular conductance was lower in PEF-HF compared to HS (1.63±0.2 vs. 2.98±0.3 units; p<0.008) but PEF-HF was not different compared to S-HF (1.63±0.2 vs. 2.04±0.3 units; p<0.28). MBP (92±3 vs. 89±4 vs. 92±4 mmHg; p=0.87) and HR (71±3 to 70±3 vs. 75±3 beats/min; p<0.46) were not different between groups. However, SBS was not different between PEF-HF and S-HF (2.3±0.5 vs. 6.9±4.4 ms/mmHg; p=0.089, respectively) but PEF-HF was lower when compared to HS (2.3±0.5 vs. 8.1±0.7 ms/mmHg; p=0.047, respectively).

Conclusion:
These results point out that even though PEF-HF have a normal ejection fraction, they showed neurovascular control as impaired as S-HF with lower SBS compared to HS.
Abstract 15570: A Novel Ex Vivo Test System to Assess Cardiovascular Toxicity of HIV-Nef in PBMC From HIV Positive Donors
Authors: Clauss Matthias , Green Linden A , Wang Tina , Chelvanambi Sarvesh , Gupta Samir K
Published: July 2021

Background:
To address how cardiovascular disease is increased in HIV patients with and without therapy, we have tested the effects of HIV-infected T cell when in contact to human coronary endothelial cells (HCAEC). We found that these T cells could induce endothelial dysfunction and cell death at a much larger extent than free virus itself. We could identify HIV-Nef protein, a major pathogenic factor in HIV disease progression and HIV-induced end organ disease, as the mechanism for this finding. Because of our finding that HIV-Nef is transferred from T cells to HCAEC to induce cell death, we asked whether PBMC form HIV-infected patients can recapitulate these findings.

Methods:
PBMC were isolated from either healthy donors or from untreated HIV patients or from those on ART using standard Ficoll purification, and intracellular Nef was determined by flow cytometry and ELISA. PBMC were co-cultivated with HCAEC for 24 hours, washed off and HCAEC were analyzed for Nef by immunofluorescence microscopy representation and ELISA. Further, HCAEC were analyzed for apoptosis by TUNEL.

Results:
HIV-Nef protein was found in PBMC of untreated HIV-positive and surprisingly also in patients receiving virally suppressive anti-retroviral therapy (ART). Importantly, we could demonstrate in untreated HIV patients Nef protein transfer to HCAEC and increased induction of endothelial apoptosis (see figure, ** p<0.01). Currently, equivalent studies with PBMC from patients on ART are in progress.

Conclusion:
This study demonstrates that Nef-positive PBMC at least in untreated HIV patients can be transferred to HCAEC to cause endothelial cell apoptosis. This will be the basis for future studies analyzing the role of NADPH oxidases and reactive oxygen species in this toxic activity of Nef. Based on this assay system we can address the hypothesis that HIV-Nef plays a pivotal role in the development of cardiovascular diseases in HIV patients with or without ART.
Abstract 15615: Eligibility for Lipid Lowering Therapy Based on AHA/ACC Risk Score, Coronary Artery Calcification, and CVD Events- National Implications for the Appropriate Use of Preventive Pharmacotherapy: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Nasir Khurram , Bittencourt Marcio , Blaha Michael J , Budoff Matthew J , Blankstein Ron , Agatston Arthur , Sibley Christopher T , Shaw Leslee J , Blumenthal Roger S , Krumholz Harlan M
Published: July 2021

Background:
It is estimated that according to ACC-AHA guidelines for cholesterol management an additional 12.8 million adults including 10.4 million for primary prevention are considered for moderate-high intensity statin therapy. We sought to determine whether coronary artery calcium (CAC) testing might identify individuals who are expected to derive the most, and the least, benefit from the prescribed pharmacotherapy.

Methods:
MESA is a longitudinal, population-based study of 6,814 men and women aged 45-84 without clinical cardiovascular disease (CVD) at enrollment. The following participants were excluded from the analysis: 1100 (16%) on lipid lowering medication, 87 individuals (1.3%) with absent LDL levels, 26 (0.4%) with missing risk factors for calculation of 10-yr risk of ASCVD based on the new pooled-cohort equations as well as 634 (9.3%) aged >75 years.

Results:
The final study population consisted of 4,967 individuals (59±9 years, 47% males). Overall 255 (5.1%) hard CVD events were noted in follow-up of median 10.3 years (IQR=9.7-10.8). Based on the new guidelines (figure), 2449 (49%) were considered candidates for
moderate-high intensity statin therapy
at baseline. Of these, 41% had CAC=0 and had 5.2 CVD events/1000 person-years and 29% had CAC>100 and they had 15.2 events/1000 person-years. Among the 610 individuals who would be considered candidates for
moderate intensity statin
, 350 (57%) had a CAC=0 and an event rate of 1.5/1000 person year. CAC testing was similarly able to risk stratify individuals across increasing levels (quartiles) of ASCVD risk >7.5% (figure).

Conclusion:
Within MESA, nearly half of patients considered for statin therapy based on the new guidelines had CAC=0, and experienced a very low event rate and subsequent high number needed to treat to prevent one event. Our study findings suggest that CAC further refines the estimate of CVD risk and may facilitate informed shared decision-making regarding statin treatment.
Abstract 15648: Quantitative Evaluation of Mitral Valve Dynamics for Improved Planning of Mitral Valve Repairs
Authors: Choi Ahnryul , Rim Yonghoon , Laing Susan T , McPherson David D , Kim Hyunggun
Published: July 2021

Introduction:
Mitral valve (MV) repair with ring annuloplasty is the standard surgical technique for the treatment of mitral regurgitation (MR). Long-term studies report MR recurrence in up to 2-4% of repairs. We have developed a novel computational evaluation strategy to determine the biomechanical and physiologic characteristics of MV dynamics prior to and following virtual MV repair to help with optimal surgical planning.

Methods:
Virtual MV models from patients with large annular dilation and severe MR in the anterolateral region were created using 3D echocardiographic data sets. Two different types of annuloplasty rings were modeled in the simulation: Physio (flat) and Physio II (saddle-shaped). Proper ring size was determined using standard clinical guidelines. Computational simulations of MV function (pre- and post-repair) were performed using dynamic finite element methods. Coaptation ratio (CR) and structural stress distribution across the MVs were determined and compared.

Results:
Pathologic MVs demonstrated substantial anterolateral malcoaptation (CR=0.34, Fig. 1A). Following virtual ring annuloplasty, there was marked improvement in coaptation (CR=0.65 for Physio, CR=0.62 for Physio II). Pre-repair simulation revealed large stress concentrations over the posterior leaflet (Fig. 1B). Stress concentration decreased by 54% after virtual MV repair. The saddle-shaped Physio II ring demonstrated more evenly distributed stress reduction while the flat ring (Physio) more effectively increased leaflet coaptation.

Conclusion:
We have quantitatively evaluated patient-specific MV function before and after MV repair using a novel computational simulation protocol. Virtual ring annuloplasty simulation demonstrated sufficient restoration of leaflet coaptation and reduced stress concentration following repair. This simulation strategy has the potential for improved pre-surgical planning and intraoperative evaluation of MV repair.