bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 2775: The effect of Plasma C-Reactive Protein on Neointimal Plaque Volume at 9 Month Follow-Up After Implantation of Sirolimus Eluting Stent (SES) and Paclitaxel-Eluting Stent (PES). Intravascular Ultrasound Study
Authors: Kim Jung-Sun , Lee Byung Ho , Kim Jae-Deok , Kim Hyun-Soo , Park Sungha , Lee Sang-Hak , Ko Young-Guk , Choi Donghoon , Jang Yangsoo , Chung Namsik
Published: July 2021

Background
: The aim of this study is to identify the association of hsCRP with neointimal plaque volume at 9 month follow-up IVUS after implantation of Sirolimus eluting stent (SES) and Paclitaxel-eluting stent (PES).

Methods:
A total of 127 patients (M:F = 78:49, age 62 ± 8 years), who underwent the elective coronary stenting for a de-novo lesion were prospectively enrolled and randomized according to type of stents (64 SES, 63PES). Infarct-related lesions within 7 days were excluded. Among them, hsCRP was serially measured in 104 patients (50 SES and 54 PES) at baseline, 48 hr after and 9 month follow-up after coronary stenting. IVUS was simultaneously performed at initial, after coronary stenting and 9 month follow-up. Neointimal volume index (neotintimal volume/stent length) at 9 month follow-up was obtained using INDEC system.

Result
: Baseline clinical, angiographic and IVUS parameters after stenting of both groups showed no significant differences. hsCRP was significantly increased at 48 hrs after coronary stenting but there was no significant difference between two groups (baseline: 2.9 ± 8.7 vs. 3.6 ± 7.6 mg/L, 48 hr: 10.7 ± 21.3 vs. 13.0 ± 15.3 mg/L, 9 month: 1.0 ± 1.6 vs. 1.2 ± 1.8 mg/L). At 9 month follow-up, SES showed a significantly lower neointimal volume index (0.22 ± 0.41 vs. 1.0 ± 0.9 mm
2
, p < 0.001) and lower tendency of in-stent restenosis [1 (2.2 %) vs. 6 (12.5 %), p = 0.111] than PES. Neointimal plaque volume at 9 month was significantly correlated with hsCRP at 48 hr (r= 0.426, p = 0.004) and increase of hsCRP between baseline and 48 hr (r = 0.512, p < 0.001). Also, higher increase of hsCRP between baseline and 48 hr (β = 0.469, p = 0.006) and PES (β = - 0.345, p = 0.024) were independently associated with increased neointimal volume index at 9 month follow-up after adjusting the clinical and angiographic parameters.

Conclcusion:
Increase of hsCRP at 48 hr after coronary stenting was significantly associated with neointimal volume in drug eluting stent (DES) era. Thus, control of acute inflammation after implantation of DES, especially PES might be beneficial for reducing neointimal plaque volume.
Abstract 392: Loss of SHP Protects LDLRKO from Diet-induced Hypercholesterolemia
Authors: Hartman Helen B , Lai KehDih , Evans Mark J
Published: July 2021

CYP7A1 encodes the rate limiting enzyme for the conversion of cholesterol to bile acids. Several studies have demonstrated that elevated expression of CYP7A1 confers protection from hypercholesterolemia. CYP7A1 expression is regulated by two nuclear receptors, farnesoid X receptor (FXR) and small heterodimer (SHP). Here we demonstrate that although FXR
−/ −
and SHP
−/ −
mice have similarly elevated levels of CYP7A1, FXR
−/ −
mice have elevated serum cholesterol and triglyceride levels and serum markers of hepatic inflammation whereas the SHP
−/ −
mice do not. This suggestion of a beneficial lipid effect of the loss of SHP was confirmed in a cholesterol/cholic acid diet model, in which SHP
−/ −
mice were strongly protected form diet-induced hypercholesterolemia and hepatic inflammation. To examine the effects of the loss of SHP in a model relevant to human dyslipidemia, we generated LDLR
−/ −
SHP
−/ −
mice. The LDLR
−/ −
SHP
−/ −
mice were highly resistant to Western diet-induced elevation in serum VLDL and LDL cholesterol levels and had significantly increased levels of HDL cholesterol as compared to LDLR
−/ −
mice fed the Western diet. Further, hepatic inflammatory gene expression induced by the Western diet was abolished in the LDLR
−/ −
SHP
−/ −
mice. Surprisingly, the LDLR
−/ −
and LDLR
−/ −
SHP
−/ −
mice had nearly identical elevations in hepatic cholesterol content and repression of cholesterol regulated genes such as HMG CoA synthase and PCSK9. CYP7A1 expression was induced 10-fold by Western in the LDLR
−/ −
SHP
−/ −
mice but not in the LDLR
−/ −
. The Western diet induction of CYP7A1 expression in the LDLR
−/ −
SHP
−/ −
mice as compared to the LDLR
−/ −
(containing an intact FXR/SHP negative pathway to modulate CYP7A1 expression) may provide a basis for the protection of LDLR
−/ −
SHP
−/ −
mice, and suggests potential utility of SHP antagonists in dyslipidemia.
Abstract 2792: Cardiac Complications After Aneurysmal Subarachnoid Hemorrhage Are Associated With Outcome: A Meta-analysis
Authors: van der Bilt Ivo A , Hasan Djo , Vandertop W. P , Wilde Arthur A , Algra Ale , Visser Frans C , Rinkel Gabriel J
Published: July 2021

Cardiac complications after subarachnoid hemorrhage (SAH) occur frequently, but their prognostic significance remains unclear. We performed a meta-analysis to assess whether echocardiographic wall motion abnormalities (WMA), electrocardiographic (ECG) changes, or elevated markers for myocardial damage are related to the occurrence of delayed cerebral ischemia (DCI) or death.

Methods
All articles that reported on cardiac abnormalities after aneurysmal SAH, that met predefined criteria, and were published between 1960 and 2007 were assessed. Data were extracted on predefined methodological criteria, patient characteristics, prevalence of cardiac abnormalities, and DCI or death. We calculated pooled relative risks (RR) with corresponding 95% confidence intervals (CI) for the separate cardiac abnormalities and outcome.

Results
We included 25 studies (16 prospective), comprising 2690 patients (mean age 53 years; 35% was male). The figure

shows the univariable RRs of the determinants for death. For DCI we found a significant association with WMA (RR 2.10 [CI 1.17, 3.78]); Troponin RR 3.15 [CI 2.27, 4.38]; CK-MB RR: 2.90 [CI 1.86, 4.52]; BNP RR: 4.52 [CI 1.79, 11.39]; and ST depression RR: 2.40 [CI 1.2, 4.9]. No significant associations were found for DCI and ST elevation RR: 2.1 [CI 0.7, 5.7]; T wave abnormality RR: 0.9 [CI 0.5, 1.7]; U wave RR: 0.7 [CI 0.4, 1.3] or prolonged QT RR: 1.0 [CI 0.5, 2.3].

Conclusion
Cardiac abnormalities increase the risk of DCI and death after SAH. Future research should be directed towards elucidating the multivariable relationship between the cardiac prognosticators, the pathophysiological mechanism and potential treatment options.
Abstract 2817: The Impact of Exercise-Induced Changes in Intraventricular Dyssynchrony on the Functional Improvement in Patients with Non-Ischemic Cardiomyopathy
Authors: Kang Soo-Jin , Lim Hong-Seok , Choi Un-Jung , Choi Byung-Joo , Choi So-Yeon , Yoon Myeong-Ho , Hwang Gyo-Seung , Tahk Seung-Jea , Shin Joon-Han
Published: July 2021

Background:
We studied whether dynamic changes in LV asynchrony may affect the functional improvement of LV in medically treated patients with non-ischemic cardiomyopathy (CMP).

Methods:
Supine bicycle exercise was performed in 41 patients (age 51±12 years, EF 33±8%). Using tissue Doppler imaging, the average of peak systolic velocities of 6 basal LV segments were obtained at rest (V
b
) and peak exercise (V
p
). ΔV was calculated by [V
p
-V
b
], reflecting the contractile reserve. Dyssynchrony index (SD
4
) was defined as the standard deviation of the time to peak systolic velocities at 4 basal & mid segments of septum and lateral wall on apical 4 chamber view. ΔSD
4
was calculated as [peak exercise SD
4
- resting SD
4
]. Follow-up echocardiography was done in 35 patients after medication for 11.2±4.2 months. Functional changes of LV was assessed by ΔEF
FU
and %change of ESV (ΔESV
FU
).

Results:
Baseline SD
4
was 24±17 ms. During exercise, SD
4
increased in 24 patients (ΔSD
4
=+14±12 ms), whereas decreased in 17 patients (ΔSD
4
=-17±14 ms). ΔSD
4
correlated with ΔV (r=-0.36, p=0.021) and exercise-induced increase in MR (ΔJet/LA area (%); r=0.31, p=0.05 and ΔPISA radius at 40cm/s of aliasing v; r=0.46, p=0.003). ΔV and ΔPISA were related to the follow-up change of LV function. Especially, ΔSD
4
independently correlated with ΔEF
FU
(β= -0.82, p<0.001) and also with ΔESV
FU
(β= 0.40, p=0.021)(Fig

). However, baseline SD
4
didn’t affect ΔEF
FU
. On ROC curve analysis, sensitivity and specificity of ΔSD
4
<4.0 ms were 82% and 78% for predicting ΔEF
FU
>+5% and 70% and 63% for predicting ΔESV
FU
<-15%.

Conclusion
: Exercise-induced changes in dyssynchrony (ΔSD
4
) can predict the functional improvement in non-ischemic CMP.
Abstract 2837: Delayed Calpain Inhibition Is Neuroprotective After Transient Global Brain Ischemia
Authors: Chen Zhaoming , Frederick James R , Bevers Matthew B , Ingleton Lori P , Ma Marek , Neumar Robert W
Published: July 2021

Introduction/Hypothesis: The delay in neurodegeneration after transient global brain ischemia offers a potentially broad therapeutic window for inhibiting molecular injury mechanisms. One such mechanism, calpain-mediated proteolysis, peaks between 24 and 72 hours after transient forebrain ischemia (TFI) in rats. This study tests the hypothesis that calpain inhibition is neuroprotective when initiated 22 hours after TFI.

Methods: Male Long Evans rats (400 – 450 g) were anesthetized (halothane), mechanically ventilated, and instrumented for temperature and hemodynamic monitoring. Each underwent 10 minutes of TFI induced by reversible bilateral carotid occlusion and hypovolemic hypotension (MAP 30 mm Hg). Twenty-two hours after TFI, rats were block randomized (n=6/group) to receive either calpain inhibitor (CEP-3453 (Cephalon), 60 mg/kg IV bolus and 30 mg/kg IV infusion for 50 hours) or vehicle (normal saline IV bolus and infusion for 50 hours). Sham operated rats served as controls. Rats were euthanized 72 hours after injury and brains were processed for immunohistochemistry. Hippocampal CA1 sector calpain activity was analyzed by immunofluorescence using primary antibody that specifically detects calpain-cleaved alpha-spectrin (Ab38). Neurodegeneration was quantified by counting normal appearing Hoechst-stained neuronal nuclei in the hippocampal CA1 pyramidal layer. Ab38 immunofluorescence intensity and normal nuclei counts were compared between vehicle and CEP-3453 treatment groups using a two-tailed Student’s t-test (alpha error 0.05).

Results: Baseline and post-injury hemodynamic parameters and temperature were not significantly different between vehicle and CEP-3453 treatment groups. Relative to sham operated controls, mean CA1 sector Ab38 immunofluorescence increased by 263 ± 281% in vehicle treated rats and 68 ± 147% in CEP-3453 treated rats (p=0.17). Normal CA1 pyramidal layer nuclei averaged 10 ± 12% of control in vehicle treated rats and 50 ± 42% of control in CEP-3453 treated rats (p=0.047).

Conclusion: These results suggest a causal role for calpains in delayed post-ischemic neurodegeneration, and demonstrate a broad therapeutic window for calpain inhibition in this model of transient global brain ischemia.
Abstract 2873: Association of Endothelial Precursor Colony Counts with Cardiovascular Risk Burden
Authors: Mheid Ibhar Al , Ozkor Muhiddin , Mavromatis Kreton , Sher Salman , Aznaouridis Konstantinos , Shirazi Farheen , Kamineni Tanuj K , Ali Muhammad , Ali Sarfraz , Sutcliffe Diane , Amer Muhammed , Alexander Wayne R , Taylor Robert , Quyyumi Arshed A
Published: July 2021

Studies investigating endothelial progenitor cell levels and cardiovascular (CVD) risk and outcomes have yielded contradictory information based on the assays employed. Culture assays of early ``angiogenic” endothelial cells differ from the late outgrowth ``proliferative” ones. We hypothesized that the number of colonies, representing the circulating pool of endothelial precursors, will be significantly stimulated by the presence of CVD and risk factors (RF).

Methods
We performed an ``intermediate” duration assay where peripheral blood mononuclear cells were cultured on fibronectin plates for 7 days and the number of colonies with endothelial-type cells at their periphery were counted by the same technician in all subjects. We sampled 420 subjects who either:

were healthy and free of RF (n = 36, age = 47 ± 10),

had metabolic syndrome, overt diabetes, or increased carotid thickness (n = 131, age = 59 ± 10),

had coronary artery disease (n = 206, age = 61 ± 10), or

peripheral vascular disease (n = 45, age = 64 ± 8).

Results
Endothelial precursor colony counts were lowest in the healthy subjects, higher in patients with RF, and highest in those with CVD (Figure

). These differences persisted after correcting for age.

Conclusion
Our data unequivocally demonstrates that the numbers of cultured endothelial colonies, utilizing an intermediate duration assay, are stimulated by the presence of risk factors, sub-clinical disease and overt CVD. This illustrates the presence of a reparative or compensatory regenerative response by endothelial progenitors to vascular injury. Whether an inadequate repair response is associated with increased risk needs to be further studied.
Abstract 2875: Long-Term Outcomes Following Vascular Surgery in Patients With Multivessel Coronary Artery Disease: Analysis of Randomized and Excluded Patients from the Coronary Artery Revascularization Prophylaxis (CARP) Trial
Authors: Garcia Santiago , Ward Herbert B , Moritz Thomas , Littooy Fred , Goldman Steve , Pierpont Gordon , Larsen Greg , Reda Domenic , McFalls Edward O
Published: July 2021

Background: The Coronary Artery Revascularization Prophylaxis (CARP) Trial was a multicenter randomized study that showed no long-term survival benefit with revascularization prior to elective vascular surgery in patients with stable coronary artery disease (CAD). To determine whether subsets with high-risk anatomy benefited from preoperative revascularization, survival was determined in randomized and registry patients who underwent coronary angiography within 6 months of vascular surgery.

Methods: Over a 4-year enrollment period, 4,876 patients were screened prior to vascular surgery and 1,048 (21.5%) had preoperative coronary angiography for either multiple cardiac risks or an abnormal preoperative stress test. The cohort included 462 randomized and 586 excluded patients and the probability of survival was determined at 2.5 years following vascular surgery.

Results: Of 1,048 patients with preoperative coronary angiography, non-obstructive disease (< 70%) was present in 192 (18.3%) and 1 vessel disease (VD) was present in 244 (23.3%), with a combined survival of 0.84. Previous bypass surgery (CABG) was present in 225 (21.5%), with a survival of 0.78. High risk coronary anatomy in patients without prior CABG included 2-VD in 204 (19.5%), 3-VD in 130 (12.4%) and an unprotected left main stenosis > 50% in 48 (4.6%) patients. Their long-term survival according to the preoperative revascularization status is shown in the Table

.

Conclusions: The results demonstrate that an unprotected left main stenosis was present in 4.6% of high-risk patients presenting for vascular surgery and was the only anatomical subset that demonstrated a survival benefit with preoperative revascularization prior to vascular surgery. These data may warrant additional strategies to identify patients with unprotected left main disease either prior to or immediately following vascular surgery.

Long-Term Probability of Survival at 2.5 Years Following Vascular Surgery
Abstract 2897: Targeting Engraftment of Endothelial Progenitor Cells to Ischemic Tissue by Ultrasound-mediated Transfection of Stromal Cell Derived Factor-1
Authors: Kuliszewski Michael A , Kobulnik Jeremy , Lindner Jonathan R , Stewart Duncan J , Leong-Poi Howard
Published: July 2021

The homing of endothelial progenitor cells (EPC) to sites of ischemic injury is critical to successful neovascularization. We hypothesize that ultrasound-mediated (UM) transfection of stromal-cell derived factor-1 (SDF-1) would enhance engraftment of exogenously administered EPCs and improve neovascularization in a rat model of chronic hindlimb ischemia.

Methods:
Bone-marrow derived EPCs were isolated from donor F344 rats, cultured for 7 days, labelled with CMTMR and injected (1 x 10
6
) into recipient animals via a jugular vein. Unilateral hindlimb ischemia was created by iliac artery ligation in 32 rats. At day 14 post ligation, microvascular blood volume (MBV) and blood flow (MBF) in the hindlimb muscles were assessed by contrast-enhanced ultrasound (CEU). Rats were assigned to 4 treatment groups: control untreated animals, EPCs alone, UM delivery of SDF-1 plasmid (500 μg DNA + 1x10
9
cationic microbubbles), and
both
UM delivery of SDF-1 + EPCs (n=8 per group). Perfusion was re-assessed at day 28. EPC engraftment was assessed using fluorescent microscopy. Circulating exogenous EPC numbers were determined by FACS at various time-points post injection.

Results:
Prior to EPC delivery, normalized MBV and MBF in ischemic muscle were similarly reduced in all groups. Control animals showed no changes in perfusion over time. By day 28, EPC treated animals had a significant increase in normalized MBV (1.04±0.24
vs
0.67±0.22, p<0.001), without significant improvements in MBF (0.44±0.13
vs
0.33±0.15, p=NS), while SDF-1/EPC treated animals had significant improvement in both normalized MBV (1.33±0.51
vs
0.67±0.22, p<0.001), and MBF (0.55±0.26
vs
0.33±0.15, p<0.001). Maximal exogenous circulating EPCs could be detected at 72 hours post injection. Fluorescent microscopy showed little to no CMTMR labelled cells in the non-ischemic hindlimb in all groups. In comparison, a rich population of cells was found in the ischemic hindlimb of both the SDF-1/EPC and EPC treated animals, with the SDF-1/EPC animals demonstrating the greatest density of EPCs.

Conclusions:
Ultrasound-mediated transfection of SDF-1 improves intravenous EPC targeting, enhancing EPC engraftment into chronically ischemic tissue and leading to greater neovascularization response.
Abstract 2965: Mutations in
SNTA1-
Encoded Syntrophin α: Characterization of a Novel Long QT Syndrome Susceptibility Gene Involving the Sodium Channel Macromolecular Complex
Authors: Medeiros-Domingo Argelia , Valdivia Carmen , Vatta Matteo , Farrugia Gianrico , Makielski Jonathan C , Ackerman Michael J
Published: July 2021

Background: Genes encoding sodium channel interacting proteins (ChIPs) have been identified as novel long QT syndrome (LQTS)-susceptibility genes. Approximately 25% of patients with LQTS remain genotype negative. ChIPs comprising the sodium channel macromolecular complex represent attractive candidates for disease susceptibility. Previously, in human jejunal circular smooth muscle, we demonstrated that syntrophin γ2 regulates sodium channel gating by a PDZ-domain interaction involving the C-terminus. In the heart, syntrophin α is more highly expressed than γ2, therefore, syntrophin α was evaluated as a possible LQTS-susceptibility ChIP.

Methods: Comprehensive open reading frame/splice mutational analysis of syntrophin α was performed using PCR, DHPLC, and direct DNA sequencing on a cohort of 50 unrelated patients with LQT1–10 negative/phenotype positive LQTS (34 females; average age at diagnosis 26 ± 16 years; average QTc 531 ± 60.4 ms; QTc range 480 –759 ms). Mutations were engineered by site-directed mutagenesis and transiently expressed in HEK293 cells containing the stably-expressed
SCN5A-
encoded sodium channel α subunit (hNaV1.5).

Results: Analysis of syntrophin α, encoded by
SNTA1
, revealed 3 missense mutations in 2 patients (4%). A female diagnosed with LQTS at 13 years (QTc, 480 ms) with family history of autopsy-negative unexplained sudden death, was compound heterozygous for P74L/A257G while a male, diagnosed with LQTS at 18 years following syncopal episodes (QTc, 529 ms), hosted the A390V mutation. These mutations were absent in 600 reference alleles and A257G and A390V involved highly conserved residues. Functional studies revealed a marked leftward shift in sodium current activation for A257G and a significant rightward shift in channel inactivation for A390V-SNTA1. Both kinetic perturbations precipitated a ``gain-of-function” increase in the sodium channel window current.

Conclusion: We provide the sentinel report of
SNTA1
as a novel LQTS-susceptibility gene with a putative pathogenic mechanism involving a secondary ``gain-of-function” in the NaV1.5 sodium channel. Thus, CAV3-LQTS (LQT9), SCN4B-LQTS (LQT10), and now SNTA1-LQTS represent functional homologues with LQT3-like perturbations.
Abstract 2968: Postmortem Genetic Testing of the GPD1-L-Encoded Glycerol-3-Phosphate Dehydrogenase 1-Like Protein in Sudden Infant Death Syndrome
Authors: Van Norstrand David W , Valdivia Carmen R , Tester David J , Ueda Kazuo , London Barry , Makielski Jonathan C , Ackerman Michael J
Published: July 2021

Introduction: Approximately 10 – 15% of sudden infant death syndrome (SIDS) may be caused by cardiac channelopathies including Brugada syndrome (BrS). Type 1 BrS (BrS1), due to mutations in the SCN5A-encoded sodium channel, accounts for approximately 20% of BrS. Recently, a novel mutation in glycerol-3-phosphate dehydrogenase 1-like (GPD1-L) disrupted trafficking of SCN5A in a multi-generational family with BrS. We hypothesized that mutations in GPD1-L may be responsible for some cases of SIDS.

Methods: Using DHPLC and direct DNA sequencing, we performed comprehensive open reading frame/splice site mutational analysis of GPD1-L on genomic DNA extracted from necropsy tissue of 228 anonymous cases of SIDS (86 females, 142 males, average age = 3 + 2 months, range 6 hours to 12 months).

Results: Three putative, SIDS-associated GPD1-L missense mutations, E83K, I124V, and R273C, were discovered in a three-month-old white male, a five-week-old white female, and a one-month-old white male, respectively. All mutations occurred in highly conserved residues and were absent in 600 reference alleles. Compared to wild type GPD1-L, GPD1-L mutations co-expressed with SCN5A in heterologous HEK cells produced a 60% reduction in peak sodium current density (p<0.004). Adenovirus-mediated gene transfer of the E83K-GPD1-L mutation into neonatal mouse myocytes markedly attenuated the sodium current as well (p<0.01). These decreases in current density are consistent with sodium channel loss-of-function diseases like BrS.

Conclusion: This study is the first to report mutations in GPD1-L as a pathogenic cause for a small subset (~1%) of SIDS via a secondary loss-of-function mechanism whereby perturbations in GPD1-L precipitate a marked decrease in the peak sodium current and a potentially lethal, BrS-like pro-arrhythmic substrate.
Abstract 2988: Changes in Coronary Revascularization Treatment Patterns Among Diabetic Patients: Results from the U.S. Medicare Program
Authors: Ryan Jason , Linde-Zwirble Walter , Engelhart Luella , Cooper Liesl , Cohen David J
Published: July 2021

Background
: Recent studies have shown that the introduction of drug-eluting stents (DES) has led to increasing use of PCI and declining use of CABG as the primary mode of coronary revascularization. Diabetic patients may be uniquely affected by these changes in revascularization patterns since studies have suggested a benefit of CABG over PCI in these patients.

Methods
: We used the Medicare 5% Standard Analytic Files to examine the selection of revascularization procedures, clinical outcomes, and costs in the year following PCI or CABG among unselected diabetic patients, aged ≤ 65 treated in 2001 (pre-DES) and 2004 (post-DES). Costs were assessed from the Medicare program perspective in 2006 dollars.

Results
: From 2001 to 2004, the revascularization rate among diabetic Medicare beneficiaries remained stable, while the proportion treated with initial PCI increased (65.2% to 73.7%, p<0.001). Over a median follow-up period of 13.5 months, there was no significant difference in mortality while the incidence of MI decreased (see Table

). After excluding repeat procedures during the index quarter, the incidence of any repeat revascularization decreased by 1.8% as well (p<0.001). Cardiovascular (CV)-related costs decreased by $1857 (p<0.001) per patient, with ~50% of the reduction occurring in the index hospitalization ($939, p<0.001). Overall medical care costs decreased more modestly due to a parallel increase in non-CV related costs.

Conclusion
: Among diabetic Medicare beneficiaries, the introduction of DES was associated with a substantial shift in the proportion of patients treated with PCI vs. CABG as an initial revascularization strategy. These changes were associated with improved clinical outcomes and lower total CV-related costs per revascularization patient at ~1 yr.

Outcomes and costs at 13.5 months after initial revascularization
Abstract 2994: Atherosclerotic Plaque Histology Predicts Restenosis after Carotid Endarterectomy: a Prospective Cohort Study in 500 Patients.
Authors: Hellings Willem E , Moll Frans L , De Vries Jean-Paul P , De Kleijn Dominique , Pasterkamp Gerard
Published: July 2021

Introduction:
Many studies have addressed clinical and angiographic risk factors for restenosis development after vascular interventions, but the composition of the atherosclerotic plaque at the intervention site has not been studied as a determinant of luminal re-narrowing after intervention. The aim of this study was to investigate the association between atherosclerotic plaque histology at baseline and restenosis development after carotid endarterectomy.

Methods:
Patients undergoing carotid endarterectomy were included in a longitudinal vascular biobank study. After surgical excision, the plaques were subjected to histological examination. The patients were prospectively followed-up with duplex ultrasound to assess restenosis (cut-off points: >50% and >70% renarrowing) one year after the intervention. The risk of restenosis was related to predefined plaque histological characteristics (macrophage and smooth muscle cell infiltration, collagen, calcifications, intra-plaque bleeding, luminal thrombus and lipid core size) adjusted for clinical characteristics (multivariable logistic regression analysis). Measurements of vessel diameter and intima-media thickness were performed using B-mode ultrasound in a subgroup of patients to discriminate between the roles of geometric vascular remodeling and neointima formation during follow-up.

Results:
In 500 consecutive patients (April 2002 – April 2007), plaque macrophage infiltration and a large lipid core were strongly associated with decreased risk of >50% restenosis (adjusted odds ratio = 0.43 [0.26 – 0.70]; 0.38 [0.19 – 0.70]) and >70% restenosis during follow-up (adjusted odds ratio = 0.36 [0.18 – 0.74]; 0.42 [0.17–1.03]), independent of clinical characteristics. The other histological characteristics were not related with restenosis. Duplex measurements (n=50) showed that vessels holding macrophage rich plaques revealed increased expansive geometric vascular remodeling during 1 year follow-up (+1.19 mm [0.03 – 2.36]).

Conclusions:
The absence of plaque macrophages and lipid core are powerful independent predictors of restenosis development after carotid endarterectomy. Plaque composition is linked with restenosis via geometric vascular remodeling.
Abstract 3016: Spirituality and Medication Adherence in Older African American Adults Diagnosed with Hypertension: A Qualitative Study
Authors: Lewis Lisa M
Published: July 2021

Background
: Medication adherence (ADH) is key to decreasing hypertension (HTN)-related morbidity and mortality in older African-American (AA) adults. However, older AA adults have poorer ADH to prescribed antihypertensive medications when compared to their younger and Caucasian-American counterparts. Patient beliefs and cultural concepts about their medications influence their medication ADH. An important cultural concept in this regards is spirituality, which is a significant resource in the AA community. Thus, the purpose of this qualitative study was to explore the role of spirituality in ADH to antihypertensive medications for older AA adults.

Methods:
Older AA adults who were members of a Program of All Inclusive Care for the Elderly (PACE) and who were (a) diagnosed with HTN; (b) prescribed at least one antihypertensive medication; (c) self-identified as African-American or Black; and (d) self-identified as spiritual completed one in-depth individual face-to-face in this qualitative descriptive study informed by grounded theory. Demographic data were also collected.

Results
: Twenty-one PACE members completed the study. All of the participants were female. The mean age of participants was 73 years with most completing high school (67%). The mean HTN diagnosis was16.7 years and mean number of prescriptions for antihypertensives was 3.3. Participants indicated that their spirituality was used in a collaborative process with formal health care to manage their ADH to antihypertensive medications. This process was identified as Partnering with God to Manage My Medications. Partnering with God to Manage My Medications indicated that the PACE members acknowledged personal responsibility for adhering to their antihypertensive medication regimen but used their spirituality as a resource for

making decisions to remain adherent;

coping with medication side effects; and

increasing their self-efficacy to deal with barriers to ADH .

Conclusions
: Spirituality played a positive role in medication adherence for the PACE members. Incorporating individual beliefs, such as spirituality, into patient treatment for HTN may capitalize on their inner resources for medication ADH and demonstrates culturally appropriate care.
Abstract 3024: Autogenic Training to Manage Chest pain in Women with Angina and Normal Coronary Arteries.
Authors: Asbury Elizabeth A , Kanji Nasim , Ernst Edzard , Barbir Mahmoud , Collins Peter
Published: July 2021

Background:
Women with angina pectoris, a positive exercise ECG for myocardial ischaemia and angiographically smooth coronary arteries (Cardiac Syndrome X), suffer increased psychological morbidity, debilitating symptomology and a poor quality of life. Autogenic Training (AT), a hypnosis-based auto-suggestive relaxation technique improved anxiety and quality of life in patients with CHD, multiple sclerosis and breast cancer. An exploration of AT as a treatment for Syndrome X was therefore undertaken.

Methods:
Fifty three female Syndrome X patients (mean ± SD; 57.4 ± 8.0 yrs) were randomised to an 8-week group-based AT and symptom diary program or symptom diary only control. Weekly group AT sessions were supported by an individual home program. The Hospital Anxiety and Depression Scale (HADS) Spielberger State-Trait Anxiety Inventory (STAI) Cardiac Anxiety Questionnaire (CAQ) and the Ferrans & Powers Quality of Life Index (QLI) were completed pre- and post-intervention and at 8-week follow-up.

Results
: Post-intervention, AT patients had reduced symptom severity (2.08 ± 1.03 vs. 1.23 ± 1.36, p=0.02) and frequency (6.11 ± 3.17 vs. 1.66 ± 2.19, p<0.001) with improved severity (8.04 ± 10.08 vs. 1.66 ± 2.19, p<0.001) and a trend toward reduced symptom frequency (1.95 ± 1.19 vs. 1.23 ± 1.36, p=0.063) compared to controls. Following AT, improved QLI health functioning (17.80 ± 5.74 vs. 19.41 ± 5.19, p=0.04) and CAQ fear (1.53 ± 0.61 vs. 1.35 ± 0.56, p=0.02) were found, with improvements in QLI health functioning (17.80 ± 5.74 vs. 20.09 ± 5.47, p=0.01), CAQ fear (1.53 ± 0.61 vs. 1.30 ± 0.67, p=0.002) CAQ total (1.42 ± 0.54 vs. 1.29 ± 0.475, p=0.04), STAI trait anxiety (42.95 ± 11.19 vs. 38.68 ± 11.47, p=0.01) and QLI quality of life (20.67 ± 5.37 vs. 21.9 ± 4.89, p=0.02) at follow-up. Post-monitoring changes in HADS depression (5.1 ± 3.3 vs. 4.2 ± 3.2, p=0.01), total HADS (13.95 ± 6.84 vs. 12.22 ± 5.75, p=0.02), CAQ avoidance (1.51 ± 0.92 vs. 1.24 ± 0.89, p=0.03), attention (1.33 ± 0.78 vs. 1.16 ± 0.57. p=0.05) and CAQ total (1.39 ± 0.6 vs. 1.23 ± 0.52, p=0.01) were shown in the control group. None were maintained at follow-up.

Conclusion
: An 8-week AT program has been shown to improve symptom severity and frequency, psychological morbidity and quality of life in women with Cardiac Syndrome X.
Abstract 419: Cytokine-Mediated Release of Vascular Endothelial Growth Factor and Stromal-Derived Factor 1 Induces Neovascularization and Prevents Left Ventricular Remodeling in a Porcine Model of Ischemia Reperfusion.
Authors: Angeli Franca S , Jahn Sarah , Amabile Nicolas , Orcino Gina , Shapiro Mia , Burjonroppa Sukesh , Minasi Petros , Chatterjee Kanu , Grossman William , Yeghiazarians Yerem
Published: July 2021

Cytokine therapy has been suggested to improve left ventricle (LV) function after myocardial infarction (MI). The mechanisms for this benefit remain debatable. We investigated the impact of a prolonged combined therapy with Darbepoetin alfa (DARB) and Granulocyte Colony-Stimulating Factor (G-CSF) on LV function and vascular density after MI, correlating it with circulating progenitor cells (CPC), Vascular Endothelial Growth Factor (VEGF) and Stromal-Derived Factor 1 (SDF-1) release.

Methods and Results
: MI was induced in swine by a 90 minutes balloon occlusion of the left anterior descending artery. Animals were divided between treatment group with DARB-GCSF combination therapy (bolus of DARB 0.9 and GCSF 10ug/kg IV at time of reperfusion, followed by 5 doses of GCSF 5ug/kg SC from day 5 to 9, and four doses of 0.45ug/kg DARB SC once per week starting at day 1, n = 8) or control group (saline injections, n = 8). White blood cells (WBC), CPC, defined by CD45, CD31, CD90 and SLA-1 expression, and circulating levels of VEGF and SDF-1 were assessed at baseline (T0), 1 (T1), 2 (T2), and 3 (T3) weeks post-MI. LV function was assessed by echocardiography at T0, T1 and T6 (6 weeks post-MI), and vascular density by histology at T6. MI size was the same in both groups by post-MI CPK peak and LV ejection fraction (EF) at T1 (41+/−1 vs. 40+/−2%). In the treatment group only, from T0 to T1, there was an increase in WBC (16 ± 2 to 42 ± 2 x 10
6
/ml, p <0.01) and CPC (5 ± 1 to 9 ± 1 x 10
5
/ml, p = 0.01) and SDF-1 levels peaked from T0 to T2 (1345+/−60 to 1554 +/− 60 pg/ml; p<0.01) and stabilized at T3. All these values remained unchanged in the control group. VEGF levels (pg/ml) peaked at T2 in both groups (14+/−1 vs. 12+/−1), but remained increased at T3 in DARB-GCSF group only (13+/−1 vs. 9+/−1; p<0.01). LVEF (41+/−1 vs. 33+/−1, p<0.01) and arteriole density at the infarct zone (44+/−14 vs. 27+/−12/mm
2
, p = 0.02) and remote zone (18 +/−8 vs.11+/−5, p = 0.055) were higher compared to the control at T6.

Conclusion
: Our data suggest that prolonged therapy with DARB-GCSF combination after MI modulates angiogenesis and promotes stabilization of LV function by increasing CPC, and releasing SDF-1 and VEGF. This therapy provides a novel strategy to prevent post-MI LV remodeling and potentially improve outcome.
Abstract 3062: Minimally Invasive Epicardial Injection Using a Miniature Crawling Robotic Device Through a Subxiphoid Approach
Authors: Ota Takeyoshi , Patronik Nicholas A , Riviere Cameron N , Zenati Marco A
Published: July 2021

Itroduction:

We have developed a miniature crawling robot (HeartLander) that navigates on the surface of a heart to dedicate minimally invasive intrapericardial interventions. We performed a series of epicardial injections with the HeartLander using a beating porcine heart through a closed chest subxiphoid approach.

Hypothesis:

The HeartLander can provide precise and safe epicardial injections under the minimally invasive approach.

Methods:

HeartLander consists of two articulated modules that adhere to the epicardium using suction. The modules are each 6.5 mm tall and 8 mm wide, and include two working channels for instrumentation. Vacuum pressure and wire actuation for inchworm-like locomotion are provided through the tether of the robot. The device uses 3-D magnetic tracking for navigation, and a joystick for control input. The control software also enables semi-automated navigation to a selected target location, as well as pre-planning of injection locations after the target is reached. In 8 porcine preparations, the device was inserted into the pericardial space through a subxiphoid approach. Epicardial injection on the ventricular wall was performed with a dedicated injection needle device through the working port.

Results:

The HeartLander could precisely be maneuvered to designated targets. Injections into left ventricles (i.e. anterior, lateral, posterior walls) were successfully accomplished in all cases. Mean depth of injection was 3.1 ± 0.34 mm. Mean path length was 48 ± 10 mm. Mean speed was 22 ± 7 mm/min. Mean suction pressure and force on wires during trials was 562 ± 26 mmHg and 4.1 ± 0.9 Newton, respectively. The magnetic tracking system provided adequate visualization. Mean deviation from the target path was 0.2 ± 1.0 mm. Target acquisition was within 2.1 ± 1.4 mm. No fatal arrhythmia and bleeding were noted during the trials. There were no injuries to the heart and surrounding structures due to the robot locomotion. A histological study verified no epicardial damage.

Conclusions:

The HeartLander demonstrated successful epicardial injection on a beating porcine heart through a closed chest subxiphoid approach. This approach may facilitate the cardiac cell transplantation therapy in the field of minimally invasive surgery.
Abstract 3076: Effects of Exercise on Ventricular Mechanical Dyssynchrony in Patients with Heart Failure Currently not Recommended for Resynchronization - Results from the Dyssynchrony Induced by Ventricular Exertion in Heart Failure (DIVE-HF) Study.
Authors: Wang Yi-Chih , Yu Chih-Chieh , Hwang Juey-Jen , Lai Ling-Ping , Tsai Chia-Ti , Tseng Chuen-Den , Katra Rodolphe P. , Lin Jiunn-Lee
Published: July 2021

Background.
Resynchronization therapy has been proven to improve exercise tolerance only in heart failure (HF) patients (pts) with profoundly impaired left ventricular ejection fraction (LVEF). Whether it could be useful to other spectrum of HF pts may depend on the existence of ventricular dyssynchrony, either at rest or exercise-induced.

Methods.
We studied clinical features, ECG, and echocardiography coupled with tissue Doppler imaging (TDI) in 70 pts (38 men and 32 women, mean age 62±13 years). Among them, 60 pts with compensated HF (functional class II–III) for at least 3 months were grouped into systolic HF (SHF; EF=35–50 %, N=30) and diastolic HF (DHF; EF=50 % plus diastolic dysfunction, N=30) groups. The other 10 pts had no systolic or diastolic dysfunction are the control group. Six-minutes (stage 2) treadmill exercise tests were performed for SHF pts by modified Bruce protocol and for DHF and control pts by Bruce protocol. Dyssynchrony index (DI) represented by standard deviation of electromechanical delays of 12 LV segments was measured before and immediately after exercise.

Results.
Except for diverse clinical features and conventional echo-parameters as expected, the QRS duration was similar (mean: 93±16 ms) between the 3 groups. TDI studies showed that baseline synchronized LV contraction remained unchanged after exercise (DI: 12.4±3.6 vs. 11.8±2.9 ms,
p
=ns) in control group. With regard to the DHF group, the preexisting ventricular dyssynchrony got significantly exacerbated (DI: 52.4±10.0 vs. 62.4±12.8 ms,
p<
0.001) including 21 pts (70%) with a ≥ 10% increase of DI after exercise provocation. With a more complex response to exercise, the DI in SHF pts didn’t worsen significantly (27.0±19.2 vs. 32.8±20.6 ms,
p<
0.06). However, the proportion of DI>33 ms, considered as presence of dyssynchrony, increased from 37% at baseline to 50% after exercise, including 6 pts (20%) with post-exercise new development and 2 pts (7%) with post-exercise disappearance of ventricular dyssynchrony.

Conclusions.
Exercise-exacerbated ventricular dyssynchrony in DHF pts, and a 50% incidence of post-exercise dyssynchrony in SHF pts with LVEF between 35 to 50% may support the potential utility of resynchronization therapy to these non-indicated HF groups.
Abstract 3097: Significance of Delayed Enhancement with Contrast Enhanced Cardiovascular Magnetic Resonance in Hypertrophic Cardiomyopathy
Authors: Maron Martin S , Appelbaum Evan , Harrigan Caitlin , Buros jacki , Gibson C. Michael , Hannah Connie , Lesser John R , Udelson James E , Manning Warren J , Maron Barry J
Published: July 2021

Background.
Cardiovascular magnetic resonance (CMR) with delayed enhancement (DE) can provide
in vivo
assessment of myocardial fibrosis. DE is an independent predictor of cardiovascular morbidity and mortality in ischemic and non-ischemic dilated cardiomyopathy but its clinical significance in hypertrophic cardiomyopathy (HCM) remains unresolved.

Methods and Results.
Cine and CMR-DE were performed in 202 HCM patients (42±17 years; 71% male). DE was identified in 103 (51%) HCM patients, occupying 9±11% (range 0.2 to 51%) of LV myocardial volume, including 12% with DE > 25%. DE was present all 10 patients with ejection fraction (EF) ≤50% (i.e., end-stage phase), 9/10 (90%) with EF 51–59% and 84/182 (45%) with EF ≥ 60% (p<0.001). %DE was inversely related to EF (r= −0.4; p< 0.001), most extensive in patients with EF ≤50% (27% vs.9% for other patients, p<0.001) and an independent predictor of EF (r= −0.6; p<0.001). Of the 182 patients with normal EF ≥60%, 49 (27%) were both asymptomatic and had DE (7±7% of LV; 51% transmural), including 7 patients ≥60 years. %DE was unassociated with heart failure symptoms (p=0.1) and age (r = 0.05; p = 0.6).

Conclusions.
In a large HCM cohort, DE was common and occupied substantial areas of LV myocardium. Importantly, DE was a strong and independent predictor of evolution to “end-stage” with systolic dysfunction. However, extensive DE was also present in many patients without heart failure symptoms, suggesting that such HCM patients undergo vigilant clinical surveillance (including serial CMR) for prospective detection of changes in clinical course and LV remodeling.
Abstract 3111: Contribution of Improved Cardiorespiratory Functions to Increased Pain-Free and Maximal Walking Distance in Patients with Claudication Following Arm Ergometer or Treadmill Exercise Training
Authors: Bronas Ulf G , Treat-Jacobson Diane , Leon Arthur S
Published: July 2021

Introduction:
We previously reported that arm ergometer exercise training improves walking distance in patients with claudication similar to treadmill exercise training through unknown mechanisms. This is the first study to investigate the effects of 12 weeks of arm ergometer or treadmill training on cardiorespiratory functions during treadmill exercise testing in patients with claudication, as compared to a usual care control group.

Hypothesis:
Both arm ergometer and treadmill training will significantly improve cardiorespiratory functions, which will contribute to improvement in both pain-free walking distance (PFWD) and maximal walking distance (MWD).

Methods:
Participants (21m, 7f, mean age 65.6 yrs, 86 % smoke hx., 27% diabetes) with claudication were randomly assigned to supervised exercise training [arm ergometry (n=10) or treadmill (n=10) ] for 12 weeks, 3h/week, or to a usual care control group (n=8). Double product at stage 1 and at MWD, anaerobic threshold, and VO
2
at onset of claudication pain and VO
2
peak were assessed during a symptom-limited, graded treadmill exercise test. Changes in these functions from baseline were analyzed between groups via ANCOVA and associations between variables were determined by Pearson’s partial correlations.

Results:
Groups did not differ in baseline demographic, medical or exercise variables. There were significant differences in response of cardiorespiratory variables to training in both exercise groups compared to the control group, but no statistical differences between exercise groups. Significant moderate correlations were found between changes in all cardiorespiratory variables and changes in PFWD or MWD (Table 1

).

Conclusion:
Improvements in cardiorespiratory functions following arm ergometer or treadmill training were significantly associated with changes in PFWD and MWD, supporting systemic contributions to exercise training-related improvements seen in patients with claudication.

Changes from Baseline in Submaximal and Maximal Cardiorespiratory Variables and Walking Improvement
Abstract 3118: Different Calculations Of Ankle Brachial Index And Cardiovascular Risk Prediction
Authors: Espinola-Klein Christine , Rupprecht Hans J , Bickel Christoph , Lackner Karl , Messow Claudica M , Munzel Thomas , Blankenberg Stefan
Published: July 2021

The quotient between ankle and brachial blood pressure (ankle brachial index =ABI) is widely used for peripheral arterial disease (PAD) screening. Guidelines on ABI measurement do not uniformly define whether the higher or the lower ankle pressure should be applied to the calculation. We hypothesized that considering the lowest ankle pressure as numerator and the highest brachial pressure as denominator would increase the prognostic impact.

Methods:
In 831 patients preceding coronary angiography, ABI was calculated for both legs according to the current definition of the American Heart Association (highest ankle pressure/ highest arm pressure) and according to an extended definition (lowest ankle pressure/ highest arm pressure). For each patient the lowest ABI from both legs was used for further evaluation. 15 patients with an ABI >1.5 were excluded. PAD was defined, if an ABI of less than 0.9 could be detected in one leg with each ABI definition.

Results:
Using the current ABI definition 204 patients (25.0%) and using the extended definition 292 patients (35.8%) with PAD could be identified. Follow-up data (median 6.6 years) was available for 812 patients (99.5%) and 157 patients (19.3%) suffered from cardiovascular events (death, infarction, stroke). Event rate was significantly higher in patients with PAD (current ABI definition: PAD yes / no=28.1% / 16.3%, P<0.0001; extended ABI definition: PAD yes / no=27.4% / 14.8%, P<0.0001). Event rate was 25.0% in 88 patients with an ABI >0.9 using the current and >0.9 using the extended ABI definition. Hazard ratio (95% confidence interval) was 1.5 (1.1–2.1) for patients with PAD using the current ABI definition (P=0.02) and 1.7 (1.2–2.3) for patients with PAD using the extended ABI definition (P=0.004) compared to patients without PAD. In addition, including ABI as continuous variable improved the area under the ROC curve from 0.68 (0.63– 0.73) for a basic model to 0.70 (0.65– 0.75) for a basic model plus ABI based on current definition and 0.71 (0.66 – 0.76) for a basic model plus ABI based on extended definition.

Conclusion:
Using the highest ankle pressure the real PAD prevalence is underestimated and a group of patients at risk is overlooked. Therefore we recommend the use of the lowest ankle pressure for ABI calculation.