bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 1839: Characterization of the Mitral Isthmus during Atrial Fibrillation Ablation Using Intracardiac Ultrasound from Within the Coronary Sinus.
Authors: West J J , Norton Patrick T , Kramer Christopher M , Mounsey J P , Moorman J R , Mahapatra Srijoy , Dimarco John P , Mangrum J M , Ferguson John D 
Published: July 2021

Background: Atrial fibrillation (AF) ablation involving the mitral isthmus and/or the coronary sinus (CS) is complex and may result in circumflex artery (Cx) damage or other complications. We investigated the feasibility of intracardiac echocardiographic (ICE) imaging from within the CS to characterize mitral isthmus anatomy and guide ablation.
Methods: A 9F sheath was introduced into the CS of 30 patients prior to AF ablation. A 9F rotational ICE catheter was then advanced within the sheath to the distal CS adjacent to the lateral left atrial wall. Serial cross-sectional images to document the relations of the left atrium, Cx, CS, esophagus and pericardium were obtained at multiple points within the CS during a pull-back to the CS ostium.
Results: The Cx was < 20mm from the CS in 62/150 positions, in 25/30 patients. In these patients, the median(range) LA-Cx distance was 3.3mm(0.7–19.6mm) and median CS-Cx distance was 2.0mm(0.4–9.7mm). The esophagus was seen < 20mm from the CS in 36/150 positions, in 17/30 patients. Median CS-esophagus distance was 4.0mm(1.4–16.2mm). Proximity of the Cx and esophagus to the left atrium and CS varied considerably. The median CS-mitral annulus distance was 11.9mm(4.1–21.6mm). After CS cannulation, the ICE imaging took 5±2 minutes and required 120±60 seconds of fluoroscopy.
Conclusions: The variable relationships of the Cx and esophagus relative to the mitral isthmus can be accurately characterized by rotational ICE imaging from within the CS. This is a useful adjunct to ICE imaging from within the atria. Real-time identification of these structures could help to locate optimal ablation sites and potentially reduce complications.
Abstract 134: Extracellular ATP Inhibits Natural Killer Cell Recruitment in Inflamed Tissues and Protects Endothelial Cells From NK-Mediated Vascular Injury
Authors: Gorini Stefania , Mammi Caterina , Ferrari Davide , Callegari Giulia , Di Virgilio Francesco , Gatta Lucia , Consoli Claudia , Caprio Massimiliano , Volterrani Maurizio , Rosano Giuseppe , Stabile Eugenio , Montevergine Clinca , la Sala Andrea 
Published: July 2021

Background: Natural killer cells (NK) represent the main source of IFN-gamma that contributes to atherosclerotic plaque progression and instability. Fractalkine (CX3CL1) expressed by endothelial cells (ECs) mediate NK recruitment and elicit NK-mediated ECs killing. Moreover high CX3CL1 mRNA expression has been found in advanced atherosclerotic lesions of human arteries as well as in the deep intima of diabetic patients. Nucleotides can be massively released in the extracellular space by ECs under shear stress, activated platelets and injured cells and stimulate purinergic receptors expressed in different cell types including NK.
Hypothesis: that extracellular nucleotides modify NK responses to CX3CL1 or SDF-1 (CXCL12) and their ability to mediate vascular injury.
Methods: NK were isolated by negative immunomagnetic selection from peripheral blood of healthy blood donors and P2 receptor genes expression pattern studied by RT-PCR. NK chemotaxis was measured by transwell cell culture system followed by flow cytometric analysis of migrated cells. NK were co-cultured with HUVEC cells to analyze NK-mediated ECs killing.
Results: we show for the first time that NK express P2Y1, P2Y2, P2Y4, P2Y6, P2Y11, P2Y12, P2Y13, P2Y14 and P2X1, P2X4, P2X7 receptors. Neither ATP or UTP alone induced NK cell migration. However ATP but not UTP increased non-directional cell movement (chemokinesis). This effect was mimicked by the cell permeable cyclic AMP analogue 8-Br-cAMP and was dependent on Protein kinase A activity since it was blocked by the specific inhibitor H89. In addition, ATP but not UTP, inhibited NK cell chemotaxis to CX3CL1 whereas expression for CXCR4 and migration following CXCL12 stimulation were increased. Moreover the NK-mediated killing of HUVEC cells was downregulated following exposure to extracellular ATP.
Conclusion: CX3CL1 has been shown to participate to leukocyte adhesion to ECs and extravasation. In addition membrane bounds form of CX3CL1 expressed by ECs triggers NK cytotoxicity. ATP release from endothelial cells upon shear stress and in inflammatory states might represent a protective mechanism from NK cell-mediated cytotoxicity and point out P2 purinergic receptors as novel potential therapeutic targets.
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 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 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 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 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.
Abstract 2211: Large Differences in Efficiency Among Fontan Patients Demonstrated In Patient Specific Models of Blood Flow Simulations
Authors: Marsden Alison L , Bernstein Adam J , Spilker Ryan L , Chan Frandics P , Taylor Charles A , Feinstein Jeffrey A 
Published: July 2021

Background: Not all Fontan patients are “equal” despite similar hemodynamics using current diagnostic modalities. Recent advances in imaging and computational fluid dynamics simulations (CFDS) enable the evaluation of both previously unmeasurable parameters (e.g. efficiency (either at rest or with exercise)) and in patient-specific scenarios. We hypothesize CFDS at rest and simulated exercise will demonstrate large differences in pressure and efficiency among Fontan patients.
Methods: Using MRI-obtained anatomy and flow, time-dependent, 3-D simulations were performed using a custom finite element solver in 4 patient-specific Fontan models. Flow features, pressure, and energy efficiency were analyzed at rest and with increasing flow to simulate light, moderate and heavy exercise. Resistance boundary conditions enabled simulation at physiologic pressures and vasodilation with “exercise.”

Results: Large variations in geometry, efficiency (96 – 87% at rest, 90–75% with exercise) and mean SVC pressure were seen (figure

). Efficiency did not correlate with Fontan pressures and did not decrease linearly with increased exercise. The most efficient among these four particular patients was a traditional t-junction connection though it had one of the highest SVC pressures.

Conclusions: Geometries, efficiency and pressure levels vary dramatically among Fontan patients. Patients may have similar hemodynamic performance at rest, but large differences in both efficiency and pressure can be demonstrated during simulated exercise. CFDS and determination of patient specific efficiency may provide an additional tool for risk stratification among patients.
Abstract 2305: Pulmonary Vascular Reactivity And Prognosis In Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Skoro-Sajer Nika , Hack Nicklas , Sadushi Roela , Jakowitsch Johannes , Bonderman Diana , Kneussl Meinhard , Klepetko Walter , Lang Irene 
Published: July 2021

Hemodynamic responder status defined as an acute decrease of mean pulmonary arterial pressure (mPAP)>10mmHg and below 40mmHg is associated with improved outcome in patients (pts) with pulmonary arterial hypertension (PAH). Pulmonary vascular reactivity to nitric oxide (NO) is controversial in chronic thromboembolic pulmonary hypertension (CTEPH). We speculated that the magnitude of the acute decrease in mean pulmonary artery pressure (mPAP) after exposure to NO might reflect the degree of small vessel disease in CTEPH and thus, affect long-term outcome.
Methods: Right heart catheterization was performed in 62 (55 Â ± 15 years, 32 female) pts with major-vessel CTEPH, at baseline and during inhalation of 40ppm NO. Within 25Â±15 days patients underwent pulmonary endarterectomy (PEA). Pts were followed for 11.3Â±26 months. Predictors of survival were analyzed by Cox regression analysis, and survival was described by Kaplan-Meier curves.
Results: Significant reductions in mean pulmonary arterial pressure (mPAP; p<0.001), pulmonary vascular resistance (PVR; p<0.001) and an increase in mixed venous oxygen saturation following NO inhalation were demonstrated (p<0.001) by a paired t-test. Stepwise multivariate analysis revealed the relative change of PVR after NO inhalation as a predictor of survival. Patients whose PVR during NO inhalation declined below 789.8 dynes.s.cm-5 had significantly better outcome than patients with above median PVR. There was a strong negative correlation between the relative change of PVR under NO and recurrent pulmonary hypertension after PEA (p=0.02).
Conclusions: Patients with operable CTEPH demonstrated acute pulmonary vascular reactivity, mostly not corresponding to a complete responder status, but accounting for a wide range of decreases of mPAP [change of mPAP (%) (−10.9Â±14)] and PVR [change of PVR (%) (−17 Â±15)]. Reduction of PVR under 800 dynes.s.cm-5 after inhalation of NO was associated with better outcome. Responsiveness to inhaled nitric oxide is a predictor for mid-term survival in adult patients with CTEPH undergoing PEA.