bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 296: Bone Marrow Derived Cells Contribute to Cell Turnover in Ageing Murine Hearts
Authors: Möllmann Helge , Nef Holger M , Troidl Christian , Voss Sandra , Heil Mathias , Kostin Sawa , Weber Michael , Hamm Christian W , Elsässer Albrecht
Published: July 2021

Background: The paradigm that the heart is a terminally differentiated organ has recently been challenged since some studies reported the ability of bone marrow (BM) derived cells to transdifferentiate into cardiomyocytes after myocardial damage. However, the physiological role of bone marrow derived cells during the lifespan of an undamaged heart is widely unknown. We therefore examined the quantity and phenotype of bone marrow derived cells in aged murine hearts.

Methods: 12-week-old mice (n=20) were sublethally irradiated and BM from enhanced green fluorescent-transgenic (eGFP) littermates was transplanted. After 1 month 5 mice were sacrificed and served as control. The remaining mice were sacrificed after 18.2±1.1 months. Immunohistochemistry was performed in 10 hearts using titin antibodies to identify cardiomyocytes, vimentin for fibroblasts, sMemb for myofibroblasts, α-smooth muscle actin for smooth muscle cells, F4/80 for macrophages, BS-1 and CD31 for endothelial cells. Additionally, anti-eGFP immunostaining was used to exclude autofluorescence. Sections were analyzed using fluorescence and confocal laser microscopy. The remaining 5 hearts were digested with collagenase and cell sorting was performed for a quantification of BM-derived cells in relation to eGFP negative cells.

Results: BM transplantation was successful as FACS analysis showed 92±5% eGFP expressing leukocytes after 1 month and 78±6% after 18 months. In the juvenile hearts only few eGFP-positive cells were detected (<1 cell/mm2). Numerous eGFP-positive cells were found in left ventricular sections in the old hearts. Histological quantification revealed 9.3±3.3 cells/mm2 to be derived from BM cells. Most of these cells were fibroblasts and myofibroblasts. In addition, numerous endothelial cells and smooth muscle cells contributing to neoangiogenesis were detected. Few eGFP-positive cardiomyocytes could be identified. The cell sorting of eGFP-positive cells documented 4.8±1.9% of all cardiac cells to be derived of BM cells.

Conclusion: The present study demonstrates for the first time a substantial recruitment and accumulation of BM derived cells in the ageing myocardium suggesting their contribution in cell turnover of the heart during the lifespan of mice.
Abstract 1889: Cardiac Resynchronization Therapy With Biventricular Pacing Improves Renal Function in Heart Failure Patients With Reduced Glomerular Filtration Rate
Authors: Boerrigter Guido , Costello-Boerrigter Lisa C , Abraham William T , St. John Sutton Martin G , Heublein Denise M , Kruger Kristin M , Hill Michael R , McCullough Peter A , Burnett John C
Published: July 2021

Background:
Renal dysfunction has emerged as an important independent prognostic factor in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves functional status and left ventricular (LV) function in HF patients with ventricular dyssynchrony. We hypothesized that CRT would also improve glomerular filtration rate as estimated by the abbreviated MDRD equation (eGFR) in patients with reduced eGFR.

Methods:
This is a retrospective analysis of the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) study, which evaluated CRT in HF patients with NYHA class III–IV, ejection fraction ≤35%, QRS ≥130 ms, and stable medical regimen. Patients were evaluated before implantation and 6 months after randomization to control (CRT device OFF, n=225) or CRT (n=228). Patients were categorized according to their baseline eGFR: ≥90 (category A), 60≤eGFR<90 (category B), and 30≤eGFR<60 (category C) mL/min per 1.73m
2
. Changes in eGFR were also correlated with changes in other parameters in univariate analysis.

Results:
At baseline, reduced eGFR was associated with ischemic etiology, increased age, mitral regurgitation, and neurohumoral activation. CRT increased LV ejection fraction and decreased LV volumes and mitral regurgitation in all categories. Importantly, CRT improved eGFR (p=0.003) and reduced blood urea nitrogen (p=0.008) compared to control in category C, but not A (p=0.75/p=0.41) and B (p=0.43/p=0.89). In addition, only in category C did atrial natriuretic peptide decrease, suggesting reduced atrial distention and filling pressures with CRT in this group with impaired eGFR. In univariate analysis, changes in eGFR correlated weakly but significantly with changes in aldosterone (r=−0.22), plasma renin activity (r=−0.19, norepinephrine (r=−0.16), and mean blood pressure (r=+0.14), a pattern consistent with reduced neurohumoral activation due to increased systemic and renal perfusion pressure.

Conclusions:
CRT increased eGFR and reduced blood urea nitrogen in HF patients with reduced baseline eGFR. By improving cardiac function, CRT can indirectly improve renal function, underscoring the importance of cardiorenal interaction and providing another mechanism for the beneficial effects of CRT.
Abstract 1901: Dual-source Ct In Non-invasive Coronary Artery Angiography: Effect Of Heart Rate, Heart Rate Variability And Calcification On Image Quality And Diagnostic Accuracy In An Unselected Patient Population
Authors: Burgstahler Christof , Brodoefel Harald , Reimann Anja , Tsiflikas Ilias , Heuschmid Martin , Uysal Ines , Wurster Diana , Haeberle Ellen , Kopp Andreas F , Schroeder Stephen
Published: July 2021

Objective: The aim of this study was to assess DSCT for evaluation of coronary artery disease in an unselected patient population. Impact of heart rate, heart rate variability and calcification on image quality and diagnostic accuracy were, thereby, considered.

Subjects and Methods: 100 consecutive patients with known or suspected CAD underwent DSCT and invasive coronary angiography. Image quality (IQ) was assessed using a 4-point scale (1: excellent; 4: non-diagnostic). Accuracy of DSCT in detection or exclusion of significant stenosis (>50%) was evaluated on a per-segment and per-patient level. Effects of heart rate, heart rate variability and calcification on IQ and accuracy were analyzed by multivariate regression and between subgroups of predictor variables. Simple regression was performed to calculate thresholds for adequate IQ.

Results: Average heart rate was 64.9± 13.2 bpm, mean variability 23.6± 36.2 beats per CT-examination and mean Agatston score 786.5± 965.9. Diagnostic image quality was obtained in 90.2% of segments. Sensitivity, specificity, positive and negative predictive values for the presence of significant stenosis was: by segment 91.1%, 92.0%, 75.4% and 97.5%; by patient 100%, 81.5%, 93.6% and 100%. According to multivariate regression, IQ was significantly related to heart rate variability and calcification (P=0.025; P<0.0001); number of non-diagnostic segments was significantly affected by calcification only. Also, in a multivariate regression, calcification was the single factor with significant impact on diagnostic accuracy (P=0.0003).

Conclusion: Whilst DSCT achieves heart rate independent image quality, the latter remains prone to heart rate variability and calcification. In an unselected patient collective, calcium burden proves to be the single determinant of diagnostic accuracy.
Abstract 299: Taurine Is Essential For Cellular Osmoregulation In The Heart
Authors: Ito Takashi , Kimura Yasushi , Takai Mika
Published: July 2021

[Background] Taurine, a sulfur-containing β-amino acid, is the most abundant free amino acid in mammalian tissues, especially cardiac muscles. Taurine is reported to be beneficial for patients with congestive heart failure; however, it remains to be fully elucidated how taurine exhibits its cardioprotective effects. To address the molecular mechanisms for its cardioprotective roles, we investigated functional and morphological phenotypes in mice lacking
taurine transporter
gene (TauTKO).

[Methods and Results] Taurine content was dramatically decreased in hearts of TauTKO mice. Echocardiographic analysis revealed that TauTKO hearts showed impaired cardiac output (Fractional shortening (%): 32.3 ± 3.6 (wild) vs 22.5 ± 2.2 (TauTKO),
p
<0.05). Histological analyses showed ventricular wall thickness was thinner in TauTKO mice than wild-type littermates, which was concomitant with decreased myocyte sizes in TauTKO ventricles (211.2 ± 5.0 v.s. 153.6 ± 5.2 μm
2
,
p
<0.01). Furthermore, to analyze the changes in gene expressions in TauTKO hearts, we performed microarray analyses using total RNA from hearts muscles. Importantly, hypertonicity-inducible genes, such as hspa1a/b (heat shock protein 70), slc38a2 (amino acid transporter-2) and s100a4 (S100 calcium binding protein A4), were upregulated more than 1.7-fold in cardiac muscles of TauTKO mice, compared with control. The inductions of these genes were verified by real time quantitative RT-PCR (hspa1a/b; 4.8 ± 1.3 (fold), slc38a2; 3.3 ± 0.5, s100a4; 1.7 ± 0.13), suggesting that hypertonicity-inducible signaling pathways are activated in TauTKO hearts. Interestingly, the upregulation of these hypertonicity-inducible genes was also observed in skeletal muscles that exhibited decreased cell size in TauTKO mice, proposing the possibility that taurine-mediated osmoregulatory signals are widely utilized in various kinds of cell lineages as a novel cytoprotective system.

[Conclusion] Intracellular taurine depletion leads to cellular osmotic impairment and results in cardiac dysfunction, accompanied by myocyte size decrease. Taurine transporter could be essential for the maintenance of intracellular osmotic homeostasis in cardiac myocytes.
Abstract 302: The Importance of Adhesion in Multipotent Stromal Cell-Induced Coronary Collateral Growth/Arteriogenesis
Authors: Belmadani Souad , Prockop Darwin , Chilian William
Published: July 2021

Because of the potential of stem cells and stromal cells to differentiate into vascular cells, their most salubrious role in the treatment of patients with ischemic heart disease may be as prophylactic agents preventing infarction by stimulating coronary collateral growth (CCG). Therefore, we determined if multipotent stromal cells (MSCs: CD59+, CD90+) would amplify CCG in a rat model of ischemia, but without infarction. Rats were instrumented with a pneumatic snare around the left anterior descending artery and subjected to repetitive ischemia (RI: 24 40 sec occlusions/day for 10 days) to stimulate CCG. CCG was determined from the ratio of flows (radioactive microspheres) to the collateral-dependent (during LAD occlusion) and normal zones (CZ/NZ, where 1.0, indicates CCG has completely restored flow to the area at risk). After RI, CZ/NZ was 0.33±0.04, which was greater than in shams indicating RI stimulated collateral growth. In rats treated with MSCs (intraventricular injection of 8 x 10
5
at the time of initial surgery), CZ/NZ was 0.51±0.01 (p<0.05 vs RI). Because the RI protocol does not produce severe tissue injury, we reasoned that the multipotent stromal cells might not home properly to the tissue; therefore we determined if amplification of MSCs adhesion would augment CCG. To accomplish this we ascertained that MSCs adhesion to endothelial monolayers in vitro was augmented (~3X) by treatment with EGF, that we found to upregulate adhesion molecule expression. Injection of EGF-treated MSCs increased CZ/NZ to 0.75±0.07 (p<0.05 vs RI and RI+BMSC). Labeling of MSCs with DiI showed that EGF treatment increased the number of labeled cells in the myocardium and vascular tissues. The fraction shortening (FS, echocardiography) was significantly decreased in the RI group 25.4±0.5% vs sham (37.2±0.3%, p<0.05 vs RI). However, injection of EGF-treated MSCs increased FS significantly (33.4±1.3%) vs RI and RI+MSCs (p<0.05), demonstrating that the increase in collateral flow was functionally significant. Thus MSCs may prove to be effective therapies for the stimulation of coronary collateral growth, but appear to be more effective after interventions are employed to increase their adhesion and homing (in vitro EGF treatment) to the jeopardized myocardium.
Abstract 2012: Relationship Between Adrenaline Concentration and Postresuscitation Syndrome in Patients with Return of Spontaneous Circulation (ROSC) After Out-of-Hospital Cardiac Arrest
Authors: Nishikawa Kei , Nagao Ken , Kikushima Kimio , Watanabe Kazuhiro , Tachibana Eizo , Mukohyama Takeo , Tominaga Yoshiteru , Tada Katsushige , Chiba Nobutaka , Ishii Mitsuru , Kasai Asuka , Soga Taketomo , Matsuzaki Masakazu , Ikeda Harumi , Tateda Yutaka , Yagi Tsukasa
Published: July 2021

Background
Although there is evidence that epinephrine hydrochloride favors initial ROSC, there is a paucity of evidence that it improves survival in humans. The value and safety of the Î
2
-adrenergic effects of epinephrine is controversial because they may lead to increase postresuscitation syndrome after ROSC. Few studies have investigated whether adrenaline concentration before epinephrine administration was related to incidence of postresuscitation syndrome.

METHODS
We did a prospective study of adult patients who achieved ROSC with standard cardiopulmonary resuscitation after out-of-hospital cardiac arrest. Blood samples to measure the adrenaline concentration were taken from a vein. The primary endpoint was neurological outcomes at hospital discharge.

RESULTS
Of the 274 adult patients with out-of-hospital cardiac arrest, 108(39%) achieved ROSC. The adrenaline levels ranged from 53 to 15,329pg/ml, with a median of 1,545pg/ml, and 25th and 75th percentile values of 707 and 4,486pg/ml, respectively. Of those, 71% (77/108) had an unfavorable neurological outcome and the adrenaline level was higher among such patients than among those with a favorable neurological outcome (a median, 2,016pg/ml vs. 938pg/ml, p=0.048). Moreover, the adrenaline level was higher among patients who died of postresuscitation syndrome within 24 hours of ROSC than among those with survival at 24 hours (a median, 3,290pg/ml vs. 1,343pg/ml, p=0.038). The adrenaline cutoff value of 944pg/ml for unfavorable neurological outcome had an accuracy of 70%. The adjusted odds ratio for the unfavorable neurological outcome after adrenaline cutoff value of 944pg/ml was 8.9 (95% CI, 2.2–35.9; p=0.002). On the other hand, the adrenaline level after epinephrine administration was 28 times as high as that before epinephrine administration (a median, 42,868pg/ml vs. 1,545pg/ml, p<0.0001).

CONCLUSIONS
In adult patients with ROSC after out-of-hospital cardiac arrest, adrenaline level before epinephrine administration was associated with incidence of postresuscitation syndrome, and the level was extremely increased after epinephrine administration. Epinephrine administration may lead to a severe toxic hyperadrenergic state in postresuscitation period.
Abstract 2019: Untrained Volunteers Perform High Quality CPR When using an Automatic External Defibrillator with a CPR Voice Prompting Algorithm
Authors: Abella Benjamin S , Kim Salem , Colombus Alexandra , Shea Cheryl L , Becker Lance B
Published: July 2021

Background:
Recent investigations have demonstrated that CPR performance among trained providers can be improved by audiovisual prompting and real-time feedback, and higher quality CPR before defibrillation can improve shock success and has the potential to improve patient outcomes.

Objective:
We hypothesized that simplified voice prompts incorporated into an automatic external defibrillator (AED) can lead to improvements in CPR performance by untrained lay rescuers.

Methods:
Adult volunteers with no prior CPR training were assessed in their use of an AED with chest compression voice instructions and metronome prompts on a CPR-recording manikin. Volunteers were given minimal instructions regarding use of the device and were given no instructions regarding CPR performance. The AED was designed to prompt five cycles of 30 chest compressions between defibrillatory attempts. Chest compression rates and depths were measured via review of videotape and manikin recording data, respectively.

Results:
A total of 60 adults were assessed in their use of the AED, with a mean age of 33.6±12.8; 36/63 (57%) were female. Mean chest compression rate was 103±12 and mean depth was 37±14 mm. Furthermore, minimal decay in chest compression rates occurred over 5 cycles of chest compressions, with mean rate of 101±19 during the first cycle and 104±10 during the 5
th
cycle. No volunteers were unable to use the AED or complete 5 cycles of chest compressions.

Conclusions:
Our work demonstrates that with appropriate real-time prompts delivered even in the absence of training or human coaching, laypersons can perform CPR that has a quality often similar to trained providers. This finding has important implications for AED design especially in light of the renewed importance of both CPR and the interaction of quality chest compressions and defibrillatory success.
Abstract 2032: Mechanistic and Prognostic Implications of “Burst” Ventricular Arrhythmias and Their Precise Timing after TIMI 3 Reperfusion in Anterior ST Elevation Myocardial Infarction
Authors: Majidi Mohamed , Kosinski Andrzej S , Al-Khatib Sana M , Smolders Lilian , Lemmert Miguel E , Pieper Karen S , Crijns Harry J , Wellens Hein J , Gorgels Anton P , Krucoff Mitchell W
Published: July 2021

BACKGROUND
Burst ventricular arrhythmias in the presence of TIMI 3 epicardial flow may reflect quality of reperfusion at a cellular level and have previously been shown to correlate with infarct size. This study aims to determine if timing of burst ventricular arrhythmias relative to reperfusion further stratifies the degree of cellular damage.

METHODS
A total of 229 anterior STEMI pts with final TIMI 3 flow from the EMERALD and CASTEMI primary PCI trials had continuous 24-hr high fidelity 12-lead ECG + Holter monitoring starting prior to PCI. Ventricular ectopy (VPC) burst arrhythmias were defined as a sudden increase over patient-specific baseline VPC rates using statistical outlier detection methodology. The time from reperfusion (defined as attainment of >50% ST recovery and TIMI 3 flow by angiography) to onset of VPC burst arrhythmias was correlated with infarct size by day 7 SPECT imaging. Continuous digital 12-lead ECG + Holter recordings, angiographic films, and SPECT images were analyzed in independent, blinded core labs.

RESULTS
Reperfusion VPC bursts were seen in 160/229 pts (70%). The presence of reperfusion VPC bursts was significantly associated with a larger infarct size (figure

). Delayed onset reperfusion VPC bursts following epicardial recanalization showed a non-significant trend towards a larger infarct size (figure

).

CONCLUSIONS
In anterior STEMI pts with successful restoration of TIMI 3 flow, reperfusion burst arrhythmias may be a unique biomarker of cellular injury with delayed burst arrhythmias signaling a worse cellular response to reperfusion. Further characterization of this unique biomarker is important to aid prognostication after reperfusion.
Abstract 2037: Renal Dysfunction and Appropriate Shock Therapy in Implantable Cardioverter Defibrillator Patients with Nonischemic Heart Failure
Authors: Takahashi Atsushi , Shiga Tsuyoshi , Futagawa Keisuke , Kimura Ryusuke , Ejima Koichiro , Manaka Tetsuyuki , Tanizaki Kouhei , Shoda Morio , Hagiwara Nobuhisa , Kasanuki Hiroshi
Published: July 2021

Background: Implantable Cardioverter Defibrillator (ICD) prevent sudden cardiac death in high risk patients with heart failure. The presence of coexisting conditions has a substantial effect on the rate of arrhythmic events in heart failure patients. Renal dysfunction is associated with mortality in patients with myocardial infarction or heart failure, but the influence of degrees of renal impairment is less well defined.

Methods: A total of 221 patients who underwent ICD implantation were included between 1990 and 2006. Gromerular Filteration Rate (GFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and renal insufficiency was defined as MDRD GFR<60mL/min/1.73m
2
. Differences in arrhythmia recurrences according to the MDRD GFR were compared by Kaplan-Meier survival curves.

Results: During a mean follow-up time of 3.7±2.8 years, 82 (37%) of 221 patients (mean age; 4.7±1.3 years, 71% male) experienced appropriate ICD shock therapy. There was a trend of higher cumulative rate of appropriate ICD shock therapies in patients with renal insufficiency than other patients (p<0.10). The result of subgroup analysis of 94 patients with low LVEF (LVEF<35%) indicated that the patients with renal insufficiency experienced electrical storms more frequently (p<0.05). After correcting for age, sex, left ventricular ejection fraction (LVEF), indication for ICD implantation, and use of beta-blockers in a Cox regression model, low MDRD GFR was still an independent predictor of the time to first appropriate ICD shock (hazard ratio [HR] 2.30, 95% confidence interval [CI] 1.13–4.69, p<0.05). Below 60mL/min/1.73m
2
, each reduction of the MDRD GFR by 10 units was associated with a HR for appropriate shock of 1.40 (95% CI, 1.00 to 1.95).

Conclusion: Renal insufficiency is associated with increased rate of arrhythmic event in nonischemic HF patients. Especially, those patients with low LVEF and renal dysfunction experience more frequent ICD shocks.
Abstract 2057: Over-expression of p27 Inhibits Vascular Smooth Muscle Cells Proliferation and Neointima Formation in Rabbit Vein Graft Model
Authors: Vassallo Paula F , Gonçalves Giovana A , Cardoso Leandro , Krieger Jose
Published: July 2021

Neointima formation caused by vascular smooth muscle cells (VSMC) proliferation is an early event in vascular remodeling associated with arterialization of vein graft and the magnitude of this process may contribute for late failure. Cell cycle is tightly regulated and cyclin-dependent kinase inhibitor p27
kip1
plays a critical role in this process. We investigated whether overexpression of p27 can modulate this early cell proliferative response in rabbit vein grafts. First generation bicistronic adenovirus AdCMVp27hEGFP, (AV1) harbouring the human p27 sequence, and AdCMVLacz (AV2) were engineered. Overexpression of p27 was analyzed by immunofluorescence and the antiproliferative effect of AV1 was assessed in primary culture of VSMC followed by 1, 3, 5, and 9 days after AV1 transduction vs. AV2. A segment of jugular vein vas exposed to AV1 and AV2 (10
9
–10
11
pfu/mL) or placebo for 30 min and then interposed, end to end, to the carotid artery of adult male New Zealand rabbits. After 28 days the vein grafts were harvested and stained with Miller for neointima analyses. Imunofluorescence of VSMC showed positive cells 72 hs following AV1 transduction. Significant inhibition of cell proliferation was observed 7 and 9 days after the cells were exposed to AV1 compared to AV2 or control cells (7 days: 0.34 ± 0.15 × 10
5
vs. 1.5 ± 0.22 × 10
5
, 2.04 ± 0.29 × 10
5
cell/ml, p<0.01; 9 days: 0.23 ± 0.1 × 10
5
vs. 1.49 ± 0.31 × 10
5
, 2.31 ± 0.41 × 10
5
cell/ml, p<0.01).
In vivo
, transduction efficiency was evaluated by the expression of B-galactosidase 48 hs. after surgery in vein grafts exposed to AV2. Vein grafts transduced with AV1 showed significant reduction in neointima hyperplasia compared with AV2 or to control animals not exposed to any viral treatment (47.33 ± 5.36 vs. 112.83 ± 24.2 and 80.08 ± 10.51μm, p<0.05). These results show that adenovirus mediated over expression of human protein p27 can inhibit VMSC proliferation
in vitro
and significantly impair the neointima formation associated with arterialization of vein graft after 28 days. It will important to establish the long term effects of this intervention specially when associated with other environment stimuli such as high fat that can clearly influence the outcome of this therapeutic intervention.
Abstract 2069: Aortic Valve Replacement In Patients With Bicuspid Aortic Valve Disease Is Not Followed By Progressive Aortic Dilatation: A 15-year Study
Authors: Ali Ayyaz , Patel Amit , Freed Darren , Abu-Omar Yasir , Sheikh Ahmad Y , Ali Ziad , Rostron Anthony , Athanasiou Thanos , Pepper John
Published: July 2021

Objectives
A bicuspid aortic valve may be associated with an aortopathy, this may lead to progressive aortic dilatation over time. It is uncertain whether the ascending aorta should be replaced prophylactically during AVR in these patients. We analyzed change in ascending aortic diameter following AVR, to determine whether a clinically important aortic pathology exists in patients with bicuspid aortic valve disease.

Methods
Demographic, operative and clinical data were obtained retrospectively through casenote review. AVR was performed using a homograft or porcine stentless valve using the subcoronary implantation technique. Patients were grouped according to whether their native aortic valve was identified as tricuspid (TC) or bicuspid (BC) at operation. Serial transthoracic echocardiograms were analyzed to measure pre-operative and post-operative ascending aortic diameter.

Results
217 patients underwent AVR between 1
st
January 1991 and 1
st
January 2001. Ninety patients had a bicuspid aortic valve, in the remaining 127 the valve was tricuspid. The bicuspid group was younger ( BC 62yr +/− 15, TC 71yr +/− 12 yrs; p < 0.001). Follow-up echocardiography was performed 6.0 +/− 4.3 years post-operatively. Pre-operative ascending aortic diameter was similar (BC 3.2 +/− 0.5, TC 3.2 +/− 0.5 cm; p = 0.56) There was no difference in the increase in ascending aortic diameter over follow-up (BC 0.1 +/− 0.5, TC 0.0 +/− 0.5 cm; p = 0.34)

Conclusion
The clinical importance of “bicuspid aortopathy” in an older age group appears to be minimal. Additional aortic procedures designed to protect against progressive aortic aneurysmal disease in this setting are not justified.
Abstract 2070: Transmural Strain Gradient of Normal, Hyperemic and Ischemic LV Walls Evaluated by New 2D Speckle Tracking System
Authors: Kimura Koichi , Takenaka Katsu , Uno Kansei , Ebihara Aya , Sasaki Kazuno , Sonoda Makoto , Abe Yasuhiko , Kawagishi Tetsuya , Nagai Ryozo
Published: July 2021

PURPOSE: Currently available 2D echo speckle tracking system can track the endocardial and epicardial echo, but cannot reliably track the speckles from the myocardium. We assessed feasibility of newly developed prototype speckle tracking system in humans with normal, hyperemic and ischemic LV.

METHODS: LV short-axis images were obtained by 2D echo (Aplio, TOSHIBA) at rest in 46 normal subjects and 52 patients with clinically diagnosed myocardial infarction (28 with non-Q wave and 24 with Q wave infarction), and during ATP infusion (0.14mg/min/kg) in 21 normals. Using the new system which could track the “myocardial” speckle (Figure

), we measured circumferential strain of the LV endocardium (Endo), mid-wall (Mid) and epicardium (Epi).

RESULTS: In normal subjects, circumferential strain showed distinct transmural gradient (p<0.001, ANOVA) (Table

). ATP infusion increased Endo strain (p<0.001) and steepened the gradient. Strain of ischemic region was extremely reduced (p<0.001) in both non-Q and Q wave infarction group and the gradient was hardly recognized in the latter.

CONCLUSION: “Myocardial” speckle tracking was feasible and can be used to evaluate the effects of coronary flow on transmural strain gradient.

Figure.

Speckle tracking of Mid as well as Endo and Epi
Abstract 2115: Results of CONTROL, a Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Study of the Effects of Tetrahydrobiopterin on Blood Pressure in Subjects with Poorly Controlled Hypertension
Authors: Quyyumi Arshed , Zieman Susan , Kakkis Emil , Hopkins John , Nicholson Martha
Published: July 2021

BACKGROUND: Tetrahydrobiopterin (6R-BH4) is a cofactor for nitric oxide (NO) synthesis. Reduced BH4 bioavailability uncouples NO synthase, decreases NO production, increases superoxide production, and may contribute to hypertension. 6R-BH4 administration has been shown to lower blood pressure (BP) and improve endothelial function in animal models and in two small, open-label clinical studies. A randomized, placebo-controlled, multicenter, parallel study was designed (‘CONTROL’) to evaluate the antihypertensive effects of 6R-BH4 in patients with treated, but poorly controlled, hypertension.

METHODS: A total of 116 subjects with hypertension (SBP/DBP> 135/85) despite a stable regimen of at least two antihypertensive drugs were randomized 2:1 to oral 6R-BH4 (n=77) or placebo (n=39) and stratified by presence or absence of type 2 diabetes. Subjects received a daily dose of 10 mg/kg 6R-BH4 for 8 weeks. Endpoints were change from baseline in SBP and DBP over 8 weeks of treatment. Other measures of efficacy included change in insulin sensitivity, proteinuria, and biochemical markers of oxidative stress and NO production.

RESULTS: 6R-BH4-treated subjects had a 4.4-mm Hg drop in SBP (baseline mean, 145 mm Hg) compared with a 6.4-mm Hg drop in placebo-treated subjects (baseline mean, 143 mm Hg; p=0.428). 6R-BH4-treated subjects had a 5.0-mm Hg drop in DBP (baseline mean, 90 mm Hg) compared with a 4.8-mm Hg drop in placebo-treated subjects (baseline mean, 93 mm Hg; p=0.907). No statistically significant differences in either endpoint were seen in subgroup analyses of subjects with or without diabetes, or in other measures of efficacy or safety. Post-hoc analyses in subjects with higher SBP at baseline (>150 mm Hg) showed a better SBP response to 6R-BH4 (−14.1 mm Hg) than to placebo (−5.9 mm Hg) however too few subjects with higher SBP were enrolled to reach statistical significance (6R-BH4, n=19; placebo, n=7: p=0.149).

CONCLUSIONS: Oral 6R-BH4 at a dose of 10 mg/kg/day showed no anti-hypertensive effect in subjects already on a stable regimen of at least two antihypertensive drugs.
Abstract 2128: Assessment Of Carotid Compliance Using Real Time Vascular Ultrasound Image Analysis In Marfan Syndrome
Authors: Kiotsekoglou Anatoli , Newey Valentine , Bajpai Abhay , Bijnens Bart , Kapetanakis Benedict , Halliday Alison , Nassiri Dariush , Camm John , Sutherland George , Child Anne
Published: July 2021

Background: The functional abnormalities in aortic root and ascending aorta in patients with Marfan syndrome (MFS) reflect reduced content of fibrillin-1 (FBN1), dysregulated cytokine transforming growth factor-β and increased collagen deposition related to FBN-1 gene mutations. Carotid arteries in MFS possibly have similar alterations which could predispose to impaired carotid compliance (CC). The aim of this study was to detect any CC abnormalities in MFS using the vascular image analysis system (VIA).

Methods: Thirty-one unoperated MFS patients, 20 men and 11 women (mean age 34.3 ± 12.2 years) and 29 normal controls matched for age, sex and body surface area (BSA) were recruited. The entire length of each carotid system was initially scanned longitudinally using a 14 MHz linear transducer. A stereotactic clamp was used to hold the transducer in contact with the carotid artery 2cm below the level of the carotid bulb. Changes in the arterial size during the cardiac cycle were continually recorded for 1 min from the right (RCCA) and left common carotid arteries (LCCA) seperately using the VIA system.

Results: CC measurements obtained from the RCCA and LCCA showed statistically significant differences between MFS patients and normal controls (RCCC: 0.126 ± 0.008 mm^2.mmHg^−1 vs 0.173 ± 0.007 mm^2.mmHg^−1, p =< 0.001 and LCCC: 0.132 ± 0.007 mm^2.mmHg^−1 vs 0.158 ± 0.007 mm^2.mmHg^−1, p = 0.007). RCCA and LCCA intima-media thickness did not differ between patients and normal controls (RCCA: 0.050 cm ± 0.001 vs 0.050 cm ± 0.001, p > 0.05 and LCCA: 0.050 cm ± 0.001 vs 0.047 cm ± 0.001, p > 0.05). In a multivariate regression analysis after adjusting for age, sex, BSA, β-blockade and systolic blood pressure (SBP), the presence of MFS associated with reduced CC, (RCCC: beta = −0.036, p < 0.001 & LCCC: beta = −0.021, p = 0.019). Sex, BSA and β-blockade showed no effect on CC, whereas age was negatively associated with CC (RCCC: beta = −0.0016, p=0.001 & LCCC: beta = −0.0015, p=0.001). SBP measurements did not differ between the two groups (119 ± 2.09 mmHg vs 114 ± 1.37 mmHg, p > 0.05).

Conclusion: Our findings suggest that despite normal intimal thickness, MFS patients have abnormal carotid compliance. This could be attributed to alterations in elastic properties related to FBN1 deficiency.
Abstract 2153: Taxus Atlas Long Lesion: First Report of 9-Month Clinical and Angiographic Outcomes for the TAXUS Liberté 38 mm Stent for Long Lesions
Authors: Turco Mark A , Ormiston John A , Popma Jeffrey J , Weissman Neil J , Webster Mark W , Cannon Louis A , Hall Jack J , O’Shaughnessy Charles D , Mann Tift , Mandinov Lazar , Koglin Joerg , Baim Donald S
Published: July 2021

Background
: The TAXUS Liberté (TL) 38 mm stent, the longest drug-eluting stent, was designed with more uniform drug distribution, thinner struts and increased flexibility and conformability for use specifically in very long lesions. Long lesions have been identified as a risk factor for instent restenosis, stent thrombosis and incomplete apposition. Thus, TAXUS ATLAS Long Lesion (LL) assesses the performance of the TL 38 mm stent vs the TAXUS Express (TE) stent.

Methods
: TAXUS ATLAS LL is a prospective, non-randomized trial enrolling 150 pts from 24 global sites. Pts undergoing single TL stent implantation of a de novo lesion visually estimated to be 26 – 34 mm in length, with a reference vessel diameter of 2.7 – 4.0 mm, were enrolled. A subset of patients underwent IVUS at 9m. The TE Control consists of a lesion-matched cohort derived from TAXUS IV and TAXUS V. The primary endpoint is non-inferiority of 9m % diameter stenosis (%DS) of the analysis segment as determined by quanitative coronary angiography (QCA).

Results
: Baseline pt characteristics were well-matched between the TL and TE arms. However, the TL pts presented with longer and more complex lesions (by QCA). Procedure time was significantly shorter for TL, and the use of multiple stents was significantly less in TL vs TE. Compared to TE, TL demonstrated non-inferiority for 9m %DS, analysis segment (pre-specified non-inferiority margin = 6.89%, difference = −0.93%, upper 1-sided 95% Confidence Interval = 3.19%, p=0.0010); thus, the primary endpoint objective was met. The cardiac death or MI rate was significantly lower for TL, while other clinical and angiographic parameters were similar between the groups. There were no stent thromboses for TL. The incidence of early or late incomplete apposition was low and comparable between TL and TE.

Conclusions
: The TL 38 mm stent, the longest drug-eluting stent, demonstrated similar efficacy in reducing stenosis but an enhanced safety profile in very long lesions vs TE.
Abstract 2161: Impact of Target Lesion Revascularization During the First Year After Bare-Metal or Sirolimus-Eluting Stenting on Five-Year Cardiac Outcomes
Authors: Mulhearn Meredith , Novack Victor , Chacko Riya S , Novack Lena , Mauri Laura , Cohen Sidney A , Leon Martin B , Moses Jeffrey , Cutlip Donald E
Published: July 2021

Background: The association of restenosis requiring target lesion revascularization (TLR) and late cardiac outcomes after drug-eluting versus bare metal stents (BMS) has not been previously assessed.

Methods: We hypothesized that restenosis requiring TLR within 1 year after stenting would be associated with increased risk of adverse cardiac outcomes during the next 4 years. Of 1058 patients randomized to sirolimus-eluting (SES) or BMS in the SIRIUS trial, 37 were excluded due to multivessel (6) or SVG (1) stenting or the occurrence of TLR within the first 30 days (30), leaving 515 SES and 506 BMS. Patients with TLR for restenosis indication between 31–360 days after the index procedure (TLR group) were compared with all others (Non TLR group) for outcomes during years 2–5. The primary endpoint was a composite of cardiac death, any MI or any repeat revascularization. The secondary endpoint was cardiac death or any MI. All events were adjudicated by an independent committee. Event rates were estimated using Kaplan-Meier (KM) method and compared using log rank. The correlates of the primary and secondary endpoints were tested using Cox proportional hazards regression.

Results: TLR occurred in 120 (11.8%) patients. TLR patients had lower frequency of SES (24.2% vs. 53.9%, p<0.001), more diabetes (35.8% vs. 25.2%, p=0.02) and smaller diameter vessels (2.7±0.5 vs. 2.8±0.5 mm, p=0.04). TLR presented with MI in 7 (5.8%) patients, including CKMB >5 times normal in 6 (5.0%) patients. The primary endpoint occurred in 42 (36.1%) TLR and 211 (24.3%) Non TLR patients (log-rank p = 0.002). Cardiac death or MI occurred in 16 (13.8%) TLR patients and 57 (6.6%) Non TLR patients (log-rank p = 0.005). TLR was an independent predictor of the primary endpoint (Hazard ratio [HR] 1.6, 95% CI 1.2–1.9) and of cardiac death or MI (HR 1.9, 95% CI 1.3–2.4). Other independent predictors of cardiac death or MI were diabetes (HR 2.2, 95% CI = 1.7–2.6) and prior MI (HR 1.9, 95% CI 1.3–2.4). SES compared with BMS was not significantly associated with the primary endpoint or cardiac death or MI.

Conclusions: Restenosis requiring TLR during 31–360 days after successful stenting is associated with an increased risk of adverse outcomes, including cardiac death or MI, in subsequent years.
Abstract 2168: Sirolimus-eluting Stent Implantation at Proximal Site Inhibits In-stent Restenosis in Bare Metal Stent Placed at Distal Site of
de novo
Lesion in Same Coronary Artery
Authors: Takano Hajime , Obata Jyun-ei , Kitta Yoshinobu , Kodama Yasushi , Mende Akira , Nakamura Takamitsu , Sano Keita , Hirano Mitsumasa , Kugiyama Kiyotaka
Published: July 2021

Drug-eluting stent (DES) suppresses peri-stent distal edge stenosis via a local diffusion of the drug. Diffusion of sirolimus into coronary blood flowing may cause an accumulation of this drug in coronary bed beyond the distal edge of sirolimus-eluting stent (SES). Thus, this study examined whether SES implantation may exert anti-proliferative action on bare metal stent (BMS) placed distally in the same coronary artery.

Methods and Results:
We prospectively examined 114 consecutive patients with stable coronary artery disease who met the following inclusion criteria:

elective, successful percutaneous coronary intervention for a long
de novo
lesion or two adjacent
de novo
lesions treated with more than two stents in the same coronary artery,

implantation of BMS (2.25 mm in size, 12 ~ 18 mm in length) in the distal site because no DES was available due to small vessel size,

quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS) at stent placement and at 6 months or during the 6 months follow up after the stenting.

At the proximal site adjacent to the distal BMS, SES was implanted without gap in 57 patients (SES-BMS), and BMS in the remaining 57 patients (BMS-BMS). Patients with in-stent restenosis (ISR, defined as > 50% diameter stenosis), developed at the proximal stent during the 6 months follow up, were excluded from the further analysis (all of them were 14 patients with BMS-BMS). Clinical, lesion, and procedural variables at stenting were comparable between SES-BMS (n = 57) and BMS-BMS (n = 43) groups. The QCA of the distal BMS showed less late luminal loss (0.49 ± 0.06 vs. 0.91 ± 0.08 mm, p < 0.01) and a lower ISR rate (13% vs. 36%, p < 0.01) in the SES-BMS group than the BMS-BMS group. The SES-BMS group also had less neointimal hyperplasia volume (25.1 ± 2.2 vs. 37.1 ± 2.5 mm
3
, p < 0.01) than the BMS-BMS group in the IVUS which examined a 10-mm length of the distal BMS from the distal edge of the proximal stent. Target lesion revascularization (TLR) of the distal BMS was less frequent in the SES-BMS group compared with the BMS-BMS group (9% vs. 19%, p < 0.01).

Conclusions:
SES implantation inhibits ISR and TLR in BMS at distal site of
de novo
lesion in same coronary artery. These findings may have an implication for stent strategy in long lesions.
Abstract 2174: Increased Platelet Aggregability In Obstructive Sleep Apnea Syndrome Patients Is Improved By Nasal Continuous Positive Airway Pressure Treatment
Authors: Horiuchi Hisanori , Sumi Kensuke , Tabuchi Arata , Taniguchi Ryoji , Oga Toru , Chin Kazuo , Mishima Michiaki , Kita Toru
Published: July 2021

Background and aim:
Obstructive sleep apnea (OSA) is a risk factor for cerebrovascular diseases. One cause for them is an occlusive arterial thrombus triggered by local platelet activation. Whether OSA is an independent risk factor for increased platelet aggregability is unclear.

Methods:
We enrolled 124 patients with snoring or daytime sleepiness in whom 3% oxygen desaturation index (3%ODI), a principal marker of the severity of intermittent hypoxia and reoxygenation (IHR), was measured. We studied
ex vivo
ADP- and collagen-induced aggregation of platelet-rich plasma using an optical aggregometer. The agonist concentration giving half maximal aggregation was defined as the platelet-aggregation threshold index (PATI) value. Therefore, the lower PATI value implicates the higher aggregability. In 23 patients who underwent nasal CPAP, platelet aggregability was followed until 90 days.

Results:
There was a significant difference in the PATI value for ADP-induced aggregation between 66 patients with non-to-mild OSA (3%ODI≤15) (1.04±0.07 μM, mean±SE) and 58 patients with moderate-to-severe OSA(3%ODI>15) (0.78±0.09 μM)(p=0.029). Multiple linear model revealed that 3%ODI strongly significantly contributed to the PATI values for ADP (p<0.001) and collagen (p=0.0026) among the 59 subjects with a cardiovascular risk factor such as smoking, hypertension, diabetes mellitus or hyperlipidemia. However, the percentage of time of arterial O2 saturation<90% during sleep did not significantly contribute to the PATI values for ADP (p=0.21) and collagen (p=0.20). After initiation of nasal CPAP therapy, the PATI values for ADP-induced aggregation significantly worsened transiently on day 30 (p=0.035), and then it recovered and improved at day 90 and the PATI for collagen-induced aggregation improved at day 90 without the transient exacerbation.

Conclusions:
OSA patients had increased platelet aggregability. Severity of IHR more significantly contributed to platelet aggregation than total hypoxic time. Among OSA patients with conventional cardiovascular risk factors, the effects of IHR on the platelet aggregability was prominent. Nasal CPAP initially induced a transient hyperaggregable state of platelets, after which it continued to improve.
Abstract 2194: Predictors of
RyR2
Genotype Among Patients Referred for Long QT Syndrome Genetic Testing
Authors: Tester David J , Will Melissa L , Ackerman Michael J
Published: July 2021

Introduction
: Type 1 catecholaminergic polymorphic ventricular tachycardia (CPVT1) is pursuant to mutations in the
RyR2-
encoded cardiac ryanodine receptor. Recently, we discovered nearly as many CPVT1-causing mutations as LQT3-causing mutations in a large cohort of unrelated LQTS referral patients. Here, we examine potential predictors of
RyR2
genotype (CPVT1) among LQTS referral patients.

Methods
: Previously, comprehensive mutational analysis of the LQT1–10 susceptibility genes was completed for 541 unrelated patients (358 females, average age at diagnosis = 24 years, average QTc = 482 ms) referred for LQTS genetic testing. Using PCR, DHPLC, and DNA sequencing, we performed targeted analysis of
RyR2
involving 44 exons (8–15, 37–49, 83–105) for the 260 unrelated referrals (172 females, average age at diagnosis = 25 years, average QTc = 470 ms) that remained “genotype-negative” following LQTS genetic testing.

Results
: Overall, 22 distinct
RyR2
mutations (19 novel) were seen in 23 (8.8%, 12 females, average age at diagnosis = 22 ±14 years) unrelated “genotype-negative” LQTS individuals. Compared to patients with either genetically proven LQTS or the remaining genotype negative cohort, the
RyR2
-positive cohort had significantly lower average QTc (419 ms vs 494 ms, p =2.4 ×10
−6
; vs 472 ms, p = 0.005) and was more likely to experience either syncope (88% vs 66%, p = 0.06 vs 53%, p = 0.008) or cardiac arrest (56% vs 23%, p = 0.006 vs 17%, p = 0.001). Overall, 123 of the 541 LQTS referrals (23%) exhibited exertion-induced cardiac events (68 LQTS gene positive; 42 gene negative, and 13 RyR2-positive). Every
RyR2
-positive case with an exertionally-triggered event had a QTc ≤ 460 ms, compared to only 17% of LQTS gene positive cases (p = 0.1 × 10
−8
) and 24% of LQT1 cases. None of the exertion-induced LQTS gene positive cases had a QTc ≤ 420 ms.

Conclusions:
Failure to distinguish CPVT from LQTS can be a fatal mistake, as individuals with CPVT1 have a more severe phenotype and are much less protected by beta blocker therapy than those with LQT1. CPVT1, rather than concealed LQT1, should lead the differential diagnosis in the setting of syncope/cardiac arrest during exercise and a normal resting QTc.
Abstract 2206: Exercise Capacity and Quality of Life late after Fontan Surgery.
Authors: d’Udekem Yves , Cheung Michael H , Setyapranata Stella , Iyengar Ajay J , Newton Melissa , Kelly Patricia , Buckland Naomi , Grigg Leeanne , Weintraub Robert G , Cochrane Andrew D , Vance Alasdair , Brizard Christian P , Penny Dan J
Published: July 2021

Objectives. Determine the exercise capacity and quality of life in a longitudinal cohort of Fontan patients and identify parameters influencing these outcomes.

Methods and Results. Fontan survivors operated in our institution and living in the same state were invited to participate in the study if they were aged more than 10 years, and free of arrhythmias. Thirty-six patients, 23 with a classical atrio-pulmonary connection (AP) and 13 with a lateral tunnel operation (LT) underwent transthoracic echocardiography, a cycloergometer exercise study, were tested for resting ANP and BNP levels, and completed the following quality of life measures: Short Form-36 Questionnaire, the Hopkins Symptom Checklist, the Dyadic Adjustment Scale and the Family Assessment Device. A mean of 17±4 years after Fontan, VO2max ranged between 14 and 34 ml/kg/min and anaerobic threshold (AT) between 11 and 34 ml/kg/min. Diastolic dysfunction was identified in 23 pts (E wave velocity z-score <−2: 17/23 pts with AP vs 6/13 pts with LT, p=0.1). ANP and BNP levels were elevated in AP Fontan and normal in LT (p0.1). The only factor predicting worse exercise capacity was the type of Fontan performed, with patients with lateral tunnel having better exercise capacity than those with atrio-pulmonary connections (percentage of predicted AT: 88±14% vs 72±14%, p<0.005; percentage of predicted VO2max: 62±8% vs 54±7%, p<0.005). Responses from quality of life measures placed our Fontan cohort within the normal population range. None of the pre and postoperative variables adversely affected patients’ quality of life.

Conclusion: Optimal blood streaming seems to be the most important determinant of exercise capacity late after Fontan surgery. Patients with lateral tunnel performed better than those with atrio-pulmonary connections. Despite limited exercise capacity, Fontan patients appear to have a normal quality of life, reflected in their reports of psychiatric symptoms and family relationships.