tbuckley/cabot-search huggingface dataset:
Abstract 17723: Non-Contrast Cardiac Magnetic Resonance BOOST Whole Heart Acquisition to Evaluate Coronaries in Children and Young Adults
Authors: Kevin K Whitehead, Matthew A Harris, Danish Vaiyani, David M Biko, Sara L Partington, Robert T Sellers, Karl P Kunze, Rene Botnar, Claudia Prieto, Mark A Fogel
Journal: Circulation (2023)

Introduction: Cardiac magnetic resonance (CMR) coronary evaluation remains challenging in teenagers and young adults using conventional respiratory navigation strategies due to irregular respiratory patterns. Motion correction strategies have shown promise in improving efficiency and quality. We sought to evaluate a non-contrast 3D whole-heart sequence with bright-blood (BB) and dark-blood (DB) phase sensitive inversion recovery (BOOST) using image-based navigation (iNAV) and a variable-density cartesian spiral profile order trajectory (VD-CASPR). Hypothesis: BOOST acquisitions improves delineation of coronary origins and proximal courses. Methods: Pts undergoing clinically indicated CMRs were prospectively enrolled and scanned at 1.5T (AVANTO FIT, Siemens) using 2 different imaging methods: 1) BOOST research sequence employing either T2 or magnetization transfer preparation at 1.0-1.4 mm isotropic resolution. When clinically indicated, 2) a standard navigated inversion recovery gradient echo sequence (IR-FLASH) acquired after gadolinium or ferumoxytol infusion. Both coronary imaging methods were rated on a 1-4 scale: 1=non-diagnostic, 2=coronary origins with significant image degradation, 3=mild image degradation, and 4=sharp delineation of the proximal coronaries. A composite BOOST score (highest score between BB and DB images) was compared to IR-FLASH. Group comparisons used a paired t-test (two-tailed, p&lt;0.05). Results: 18 pts, mean age 18.8 years (range=10-31) underwent BOOST imaging. 15 had an IR-FLASH for comparison. BOOST acquisition times were 7-12 minutes. Three pts had coronary anomalies (2 with right coronary from the left sinus, 1 single coronary). Coronary origins were delineated on all BOOST exams with a mean score=3.6 for BB BOOST and 2.9 for DB compared to 3.1 for the IR-FLASH, neither of which was significantly different. The composite BOOST mean score was 3.8, which was significantly higher than IR-FLASH. Conclusions: In our series in children and young adults, contrast-free BOOST imaging delineated coronary origins in all pts, even in challenging cases of anomalous origins. When utilizing both BB and DB BOOST images, image quality exceeded that of a conventional post-contrast IR-FLASH sequence.
Abstract 14731: T-wave Oversensing Secondary to an Inappropriate ICD Shock Resulting in Subsequent Unnecessary Shocks
Authors: Bosky Soni, Reed Melanie, Tony Anno, Brian Olshansky, Luigi Di Biase, Neil Patel, Dhanunjaya R Lakkireddy, Rakesh Gopinathannair
Journal: Circulation (2023)

Introduction: Inappropriate ICD shocks commonly result from persistent atrial arrhythmias or oversensing. We report a scenario where an ICD shock for a rapid, sustained atrial tachycardia (AT) resulted in T-wave oversensing (TWO), triggering further inappropriate shocks. Presentation: A 69-year-old woman with secondary prevention dual chamber ICD underwent pulmonary vein isolation for symptomatic paroxysmal atrial fibrillation (AF). The patient remained free of AT/AF off antiarrhythmics for 3 months after the procedure when she was admitted with four consecutive ICD shocks. Electrolytes were within normal limits. Device interrogation showed that the first shock was triggered by a rapid, sustained AT (cycle length: 270 msec) detected in the VF zone (single zone device; 280 msec cut-off) and failed ATP. Following the first shock, an irregular AT ensued, with cycle length ranging from 280-370 msec, but now with high amplitude T-waves in the RV channel, resulting in TWO and three subsequent inappropriate shocks (Figure). She received IV metoprolol and digoxin with subsequent resolution of AT and TWO. Beta-blocker dosing was increased and she has remained free of AT/AF at 6 month follow-up. Conclusions: ICD shocks can trigger marked repolarization changes in near-field intracardiac RV electrograms resulting in TWO and subsequent appropriate shocks. Further studies are warranted to understand the mechanism underlying this phenomenon and potential risk for these events.
Abstract 16552: Coronary Vasomotor Response to Intracoronary Ergonovine Provocation Test According to the Severity of an Insignificant Coronary Artery Fixed Stenosis
Authors: Seung-Woon W Rha, Byoung Geol Choi, Woo Jin Ahn, Se Yeon Choi, Jae Kyeong Byun, Jinah Cha, Sujin Hyun, Soohyung Park, Dong Oh Kang, Eun Jin Park, Cheol Ung Choi
Journal: Circulation (2023)

BACKGROUND: Coronary artery spasm (CAS) is a major cause of variant angina in patients with chest pain without significant coronary stenosis. However, whether there are differences in the incidence of CAS according to the severity of underlying coronary artery fixed stenosis is limited. Methods: A total of 608 patients without significant coronary artery disease (CAD) who underwent the ergonovine (ERG) provocation test between January 2018 and December 2021 were enrolled. Significant CAS was defined as having≥70% of temporary narrowing by ERG test. Patients were divided into three groups, based on the presence of coronary artery stenosis: None group (n=456), mild group (30-49%,n=114) and moderate group (50-69%,n=38). Results: In patients with chest pain without significant coronary artery stenosis, mild stenosis was 18.8%, and moderate stenosis was 6.3% in the population. The baseline characteristics of the patients were worse in the mild and moderate group than in the None group, including age, hypertension, diabetes, and smoking habit. In the ERG test, CAS occurred in 44.4% (270/608) of the overall population. The incidence of CAS of the mild (55.3%) and moderate (52.6%) groups were higher than the None group (41.0%). Also, in the case of CAS occurrence, focal CAS (Length&lt;20mm) was more frequent in the mild (14.3%) and moderate (30%) groups than in the no group (8.6%). CONCLUSIONS: In patients with resting chest pain without severe coronary artery stenosis, CAS was observed in a high proportion of nearly half by ergonovine provocation test. Moreover, the mild to moderate coronary artery fixed stenosis showed higher incidence of CAS and focal CAS than patients without fixed stenosis.
Abstract 13903: Pacemaker Mediated Arrhythmia Following AV Synchronous Leadless Pacemaker Implantation
Authors: Dejan Vrtikapa, Luke Chong, Daniel Modaff, Ryan T Kipp
Journal: Circulation (2023)

Background: Leadless pacemakers have gained popularity in providing permanent pacing in select patient populations. Pacemaker mediated tachycardia and arrhythmias have been well described in patients with dual chamber pacemakers, but up to this point not in leadless pacing. Case Description: A 91-year-old female with symptomatic bradycardia and 2:1 AV block underwent implantation of a Micra AV pacemaker programmed VDD 60-100 bpm. Five months later, she presented with decompensated heart failure with a heart rate of 88 bpm and a newly reduced left ventricular ejection fraction of 30%. Device interrogation showed 95% ventricular pacing, with 91% AV synchrony. The Micra was found to be tracking an atrial rhythm between 80-100 bpm more than 80% of the time (Figure 1A). RV pacing induced cardiomyopathy was suspected and she underwent placement of a bi-ventricular pacemaker. During implant, a short VA time was noted and changes in the V-V cycle length predicted changes in the A-A cycle length (Figure 1B). Micra ventricular pacing was held resulting in an AV paced rhythm from the CRT system and a drop in rate to 60 bpm (Figure 1C). These results indicate that the Micra pacemaker was tracking the atrial mechanical contraction (AM) from a retrograde conducted P-wave resulting in elevated heart rates from a pacemaker-driven arrhythmia. Discussion: In patients with poor AV conduction, intact VA conduction, and SA node dysfunction, Micra AV may create pacemaker mediated arrhythmia by tracking the AM of the retrograde conducted P-wave. Careful patient selection to avoid Micra AV placement in patients with SA node dysfunction, and close attention to the rate histogram on device interrogation may prevent development and facilitate recognition of this unique cause of pacemaker-mediated arrhythmia.
Abstract 13327: Mechanistic Basis of Sinoatrial Node Pacemaker Failure in Atrial Cardiomyopathy
Authors: Édouard Marcoux, Martin Mackasey, Patrice Naud, Martin G Sirois, T. Alexander Quinn, Stanley Nattel
Journal: Circulation (2023)

Introduction: Sinoatrial node (SAN) dysfunction commonly occurs in atrial cardiomyopathy (ACM: “tachy-brady syndrome”), often requiring pacemaker implantation, but mechanisms are unknown. Atrial-selective myosin light chain-4 (MYL-4) mutations cause familial ACM with a high rate of early SAN dysfunction and pacemaker requirement. We studied rats engineered with a knock-in MYL-4 clinical E11K mutation and addressed mechanisms of SAN dysfunction. Methods: Atrial electrical properties were assessed with in vivo electrophysiology (EPS), ex vivo optical mapping, SAN single-cell voltage and current clamp, Ca 2+ -handling with Ca 2+ -sensitive dye microscopy. Gene expression was assessed by qPCR and fibrosis with Masson-Trichrome stain. Results: E11K rats showed progressive SAN recovery-time increases (Fig. A) and conduction-slowing (Fig. B). SAN cells showed slowed phase-4 depolarization (Fig. C) and reduced pacemaker “funny” current (I f ) (Fig. D). Ca 2+ homeostasis was also affected, showing decreased Ca 2+ -transients (Fig. E). SAN also displayed remodeling with increased collagen deposition (Fig. F). Conclusions: ACM resulting from E11K mutation induces multimodal electrical and structural remodeling of the SAN region, worsening with age. These observations provide new insights into mechanisms of the clinically important tachy-brady syndrome associated with ACM.
Sphingosine-1-phosphate receptor 3 regulates the transendothelial transport of high-density lipoproteins and low-density lipoproteins in opposite ways
Authors: Srividya Velagapudi, Dongdong Wang, Francesco Poti, Renata Feuerborn, Jerome Robert, Eveline Schlumpf, Mustafa Yalcinkaya, Grigorios Panteloglou, Anton Potapenko, Manuela Simoni, Lucia Rohrer, Jerzy-Roch Nofer, Arnold von Eckardstein
Journal: Cardiovascular Research (2023)

The entry of lipoproteins from blood into the arterial wall is a rate-limiting step in atherosclerosis. It is controversial whether this happens by filtration or regulated transendothelial transport.Because sphingosine-1-phosphate (S1P) preserves the endothelial barrier, we investigated in vivo and in vitro, whether S1P and its cognate S1P-receptor 3 (S1P3) regulate the transendothelial transport of lipoproteins.
Abstract 18880: Ventricular Arrhythmia Prevalence and Burden in Patients With Third Generation Continuous Flow Left Ventricular Assist Devices
Authors: Chadi Tabaja, Younis Arwa, Tyler Taigen, Justin Lee, Mina K Chung, John Barnard, Shady Nakhla, Mandeep Bhargava, Koji Higuchi, Mohamed H Kanj, Jakub Sroubek, Walid I Saliba, Ayman Hussein, J. Emanuel Finet, Wai Hong W Tang, Oussama M Wazni, Pasquale Santangeli
Journal: Circulation (2023)

Background: Ventricular arrhythmias (VAs) are common in patients with left ventricular assist devices (LVADs). Little is known about the impact of third-generation LVADs (Heartmate 3, HM3) on VAs prevalence and burden. Aims : To characterize the impact of HM3 LVAD implantation on VAs prevalence and burden in patients with advanced heart failure (HF) and implantable cardioverter-defibrillators (ICDs). Methods: We included consecutive patients with advanced HF and ICDs who received HM3 devices at our center between 2016 and 2022. The study outcomes were the prevalence of sustained VAs, defined as &gt;30s VA episode detected by the ICD monitor zone or appropriately treated (ATP or shock), sustained VA burden (total number of episodes), and VA storm (≥3 appropriate ICD interventions in 24/h period). Data was collected over the 1 year before and after HM3 implantation. Results: A total of 321 patients were included (28% female, mean age 60±12 years, mean INTERMACS score 3±0.95). At 1 year follow-up after HM3 implantation, 27 patients died. A total of 128 patients (43%) had at least one sustained VA episode in the year before the HM3 implantation compared to 51 patients (17%) in the year following the HM3 (p&lt;0.001 for comparison). The sustained VA burden decreased from a mean of 3.8 events per person-year (PPY) to a mean of 0.8 events PPY (p=0.005). Similarly, appropriate ICD therapy occurred in 123 patients (38%) before implantation and 46 patients (14%) after implantation (p&lt;0.001). The burden of appropriate therapy was also reduced (from a mean of 2.57 events PPY to a mean 1.32 events PPY; p=0.03). The prevalence of VA storm was reduced from 19% to 8% (p&lt;0.001). Conclusions: In patients with advanced HF and ICDs undergoing HM3 implantation, the prevalence of sustained VAs, VAs burden, appropriate ICD interventions, and VA storm were all significantly reduced in the year following HM3 implantation.
Abstract 15719: Prognostic Interplay Between Myocardial Flow Reserve and Left Ventricular Ejection Fraction
Authors: Malek Nayfeh JR, Mahmoud Al Rifai, Ahmed Ibrahim Ahmed, Fares Alahdab, Mouaz Al-Mallah
Journal: Circulation (2023)

Introduction: Myocardial flow reserve (MFR), measured using positron emission tomography (PET), has been shown to add incremental prognostic value in multiple patient populations. Whether this association is modified by left ventricular ejection fraction (LVEF) is not well studied. The aim of this analysis is to determine whether there is a prognostic interplay between myocardial flow reserve and LVEF. Methods: The study population included patients who had clinically indicated PET myocardial perfusion imaging and were prospectively followed for incident events. MFR was calculated as the ratio of stress to rest myocardial blood flow (MBF) (ml/min/g). Rest LVEF was calculated from end systolic and end diastolic LV volumes on gated images. Cox proportional hazards were used to study the association between MFR (&lt;2 vs ≥2) and incident cardiovascular events stratified by LVEF (&lt;50% vs ≥50%). Results: The study population included 5,523 patients (mean±SD age 67±12 years, 53% male), 16% of LVEF&lt;50% and 47% MFR &lt;2. Rest MBF was similar among patients with normal or reduced LVEF while stress MFR was lower with lower EF. In adjusted analysis, patients with impaired MFR had a higher incident event rate regardless of LVEF (Figure 1). Patients with MFR&lt;2 had a higher risk of incident outcomes in both LVEF ≥50% (HR=2.58, 95% CI:1.93 - 3.46, p&lt;0.001) and LVEF &lt;50% (HR=2.76, 95% CI: 1.62 - 4.70, p&lt;0.001); p-value for interaction= 0.045. Conclusions: Impaired MFR is associated with a higher risk of cardiovascular outcomes and death in patients with high or low LVEF.
Abstract 13787: Restricted Coronary Flow Reserve of Mental Stress Induced Myocardial Ischemia in Angina and No Obstructive Coronary Artery Disease
Authors: huan ma, Lan Guo, Han Yin, Yuting Liu, Bingqing Bai, fengyao liu, Haochen Wang, Qingshan Geng
Journal: Circulation (2023)

Background: The myocardial blood flow (MBF) mechanism in mental stress-induced myocardial ischemia (MSIMI) in angina with no obstructive coronary artery disease (ANOCA) population is unknown. Methods: 13-NH 3 cardiac PET-CT was utilized to assess MBF and perfusion changes under mental stress (ms) and adenosine stress (as) in ANOCA subjects and gender- and age-matched healthy controls. MSIMI was defined as an increase in perfusion defect score of ≥3 points. Results: Among the 126 participants enrolled, ANOCA women showed a significantly higher prevalence of MSIMI compared to the healthy controls (36/84 vs. 1/42, p &lt;0.001). Perfusion defects under ms occurred synchronously however more pronounced in the left anterior descending and right coronary artery territories, consistent with a significantly higher MBF hyperemia in the left circumflex territory. MBF ms shows a close correlation with rate-pressure product (RPP ms ) ( p &lt;0.05 in ANOCA&amp;MSIMI+, ANOCA&amp;MSIMI-, and control groups with r pearson ranging from 0.39-0.65). Although no differences existed in absolute MBF ms values between groups, there were notable increasing trends among the three groups in corrected MBF, which reflected blood flow supply-demand balance (ANOCA&amp;MSIMI+: 0.96±0.23 vs. control group: 1.10±0.29, p =0.020), and in coronary flow reserve (CFR) (ANOCA&amp;MSIMI+: 2.41±0.75 vs. control group: 2.89±0.77, p =0.016). Furthermore, after adjusting for confounding factors, only subjects in ANOCA&amp;MSIMI+ group did not exhibit a corresponding increase in MBF ms matching MBF as . Conclusion: Restricted CFR, indicating impaired coronary microvascular function, and mismatch between myocardial blood supply and demand together constitute the pathogenic mechanism of MSIMI in ANOCA population. More researches are still needed in exploring the brain-heart interaction in MSIMI.
Abstract 19021: Metabolomic Characterization of Responses to Angiotensin Peptides in Human Brain Microvascular Endothelial Cells
Authors: Andres C Diaz-Valencia, Monica P Cala-Molina, Ricardo A Pena-Silva
Journal: Circulation (2023)

Introduction and hypothesis: Metabolomics offers a robust platform for dissecting the intricate molecular responses of biological models under distinct stimulation scenarios. The mechanism by which Angiotensin 1-7 modulates Angiotensin II signaling in endothelial cells is unclear and may involve events at the cellular membrane or downstream signaling pathways. We hypothesize that metabolomics can help us identify shared and distinct metabolic responses induced by these two molecules. Methods: hCMEC/D3 cells were cultured and then subjected to stimulation with Ang-II and Ang 1-7 during their logarithmic growth phase. Subsequent metabolomic profiling incorporated both RP-LC-QTOF-MS and GC-QTOF-MS analytical techniques. Our data analysis strategy was multilayered, implementing quality control alongside various multivariate statistical methods, such as principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and hierarchical clustering. Results: Our results underscore a discernible pattern of decreased and increased metabolite expression in response to angiotensin treatments, with noteworthy variations observed in the expression of glycerophospholipids, sterol lipids, and sphingolipids amongst the Ang-II, Ang 1-7, and control groups. Intriguingly, an "ON/OFF" pattern for numerous metabolites emerged across the experimental groups, hinting at shared biological activity provoked by both angiotensin treatments. The compounds Erucamide, Dihydroxy-chol-en-oic Acid, and LPE O-19:0;O significantly contributed to the discrimination between Ang-II and Ang 1-7 treatment groups when compared with controls. Conclusions: These findings offer a novel perspective on the distinct metabolic responses induced by Ang-II and Ang 1-7 treatments in hCMEC/D3 cells, and may shed light on the cellular mechanisms that underlie the impact of these angiotensins, and other vasoactive peptides, on the blood-brain barrier. Overall, our study reaffirms the value of metabolomics as a powerful tool for gaining new insights into the molecular effects of vasoactive peptides on endothelial cells.
Abstract 18861: Therapeutic Targeting of <i>Rpl13a</i> -Small Nucleolar RNAs Mitigates Atherosclerosis in <i>Apoe</i> <sup>-/-</sup> Mice
Authors: Brittany A Elliott, Jiao-Hui Wu, Lisheng Zhang, xinhe yin, Jeffrey K Davis, Pei-Chen Wu, Neil J Freedman, Christopher L Holley
Journal: Circulation (2023)

Specific non-coding, small nucleolar (sno) RNAs encoded within introns of the Rpl13a gene elevate cellular levels of reactive oxygen species (ROS), and ROS are known to aggravate atherosclerosis (athero). We found that genetic deficiency of Rpl13a -snoRNAs reduces brachiocephalic artery athero in Apoe -/- mice by 50%. We therefore tested the hypothesis that athero could be reduced by acute pharmacologic intervention targeting Rpl13a -snoRNAs in Apoe -/- mice. To that end, we injected male and female Apoe -/- mice subcutaneously with 48 mg/kg antisense oligonucleotides (ASOs) targeting (a) the four Rpl13a -snoRNAs (ASO-snoRNA), or (b) green fluorescent protein (ASO-control). We tested two distinct strategies: ( i ) preventive, in which ASO injections and Western diet were started in 10-wk-old mice, with 4 weekly and 5 bi-weekly ASO treatments over 14 wk, then sacrifice; and ( ii ) “therapeutic,” in which ASO injections were started in 24-wk-old mice that had been fed Western diet for 14 wk and then were continued on Western diet with 6 weekly ASO treatments and then sacrificed. ASO injections were administered as indicated until 1 wk prior to sacrifice. Compared with saline-injected mice, ASO-control and ASO-snoRNA showed no hepatotoxicity (as assessed by serum ALT and AST). Compared with ASO-control, ASO-snoRNA administration for 6 wk reduced Rpl13a -snoRNA levels in the aorta and spleen by 54-80% for snoRNAs U32a , U33 , and U34 (RT-qPCR). In the “therapeutic” cohort, brachiocephalic artery cross-sectional athero was reduced by 38% in ASO-snoRNA-treated as compared with ASO-control-treated mice (n=7/group, p &lt;0.03). Additionally, male ASO-snoRNA-treated mice exhibited a 98.1% decrease in circulating IL1-β transcripts (n=6-8/group, p&lt;0.003). In the “preventive” cohort, aortic athero was reduced by 40% (13±5 vs 7±3 % aortic lesion area, n= 11-13/group, p &lt;0.02) in ASO-snoRNA-treated as compared with ASO-control-treated mice. We conclude that therapeutic targeting of Rpl13a -snoRNAs with ASOs mitigates athero, both during the early and later stages of atherogenesis.
Abstract 14998: Assessment of Microcirculatory Dysfunction by Measuring Subcutaneous Tissue Oxygen Saturation Using Near-Infrared Spectroscopy in Patients With Circulatory Failure
Authors: Jun Sato, Atsushi Sakurai, Kosaku Kinoshita
Journal: Circulation (2023)

Background: Patients with circulatory failure have been treated with the goal of normalizing systemic hemodynamic parameters such as blood pressure, central venous pressure, urine output, and central venous oxygen saturation. However, microcirculatory dysfunction remains even after improvement of these indices, suggesting a loss of hemodynamic coherence between the macrocirculation and the microcirculation. Recently, the usefulness of near-infrared spectroscopy (NIRS) in assessing the microcirculation has been reported. Aim: We measure regional tissue oxygenation saturation (rSO 2 ) at 3 - 5 mm subcutaneously in patients with circulatory failure using a finger-mounted tissue oximeter with the NIRS technique (Toccare: Astem Co., Ltd., Kawasaki, Japan) to investigate its relationship with microcirculation. Methods: This is a single-center prospective observational cohort study of patients with circulatory failure (systolic blood pressure ≤ 90 mmHg or lactate ≥ 2 mmol/L at presentation) transported to the emergency department of Nihon University Hospital from 15 June 2020 to 31 March 2022. We measured rSO 2 in the forehead, thenar eminence, thumb and knee using Toccare and assessed the relationship between rSO 2 and blood pressure, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score and mottling score. Result: In patients with circulatory failure (n = 38), rSO 2 at each site showed no correlation with blood pressure, a negative correlation with SOFA score and APACHE II score and a positive correlation with mottling score. These significant correlations were also best observed in the knee. Conclusion: In patients with circulatory failure, rSO 2 measured with Toccare showed no correlation with blood pressure but a significant negative correlation with the severity of organ damage. The knee is possibly the optimal measurement site for monitoring microcirculatory dysfunction and determining the effectiveness of treatment.