tbuckley/cabot-search huggingface dataset:
Abstract 16587: Comparison of Risk Profile for New-Onset Atrial Fibrillation Between Young and Elderly
Authors: Pil-sung Yang, Eunsun Jang, Hee Tae Yu, Tae-Hoon Kim, Jae-Sun Uhm, Hui-Nam Pak, Moon-Hyoung Lee, Boyoung Joung, Joung-Youn Kim
Journal: Circulation (2018)

Introduction: The atrial fibrillation (AF) is heterogeneous in pathophysiology based on individual patient characteristics. A number of risk factors are associated with an increased risk for the development of AF. The aim of our study is to identify the effects of widely known risk factors for AF, on the incidence of AF according to age in general population and to find out its clinical implication. Methods: We analyzed 506,209 patients (≥18 years) without AF or valvular heart disease from the Korean National Health Insurance Service-National Sample≥ Cohort (NHIS-NSC) between 2009 and 2013. Total population is divided into two groups: “young” whose age is less than, and the “elderly,” as those older than 60. Results: Of the 3,416 (0.7%) cases of AF occurring during follow-up periods of 46.2 ± 15.1 months, 1664 (0.4%) were in young age and 1752 (2.6%) were in elderly age group (p&lt;0.001). In a multivariate Cox regression analysis, age, male gender, hypertension and heart failure were related with increased risk of AF in both group. In addition, in young age group, risk of new-onset AF incidence was increased by diabetes mellitus (HR 1.26, 95% CI 1.05-1.52, p=0.014), current or former smoking (HR 1.20, 95% CI 1.02-1.42, p=0.028), and obesity (HR 1.36, 95% CI 1.21-1.54, p&lt;0.001). In elderly age group, chronic obstructive pulmonary disease (HR 1.46, 95% CI 1.21-1.75, p&lt;0.001) and chronic renal disease (HR 1.23, 95% CI 1.06-1.42, p=0.007) increased the risk of new-onset AF. Conclusions: There was a difference in the pathogenesis of AF between young and elderly. In young age group compared to elderly age group, modifiable risk factors had a greater impact on the incidence of new-onset AF. Therefore, clearly defined management strategies to prevent and tackle this arrhythmia according age is required.
Abstract 16769: QT Prolongation and Variability Among Patients With Rett Syndrome
Authors: Gregory J Jutzy, Peter Heydemann, Colleen Buhrfiend, Hoang H Nguyen
Journal: Circulation (2018)

Introduction: Rett syndrome (RTT) is caused by mutations in the MECP2 genes resulting in various neurological, gastrointestinal, and respiratory symptoms. Prolonged corrected QT interval (QTc) is also reported and thought to be a cause of sudden death in RTT. However, characterization of QTc, its clinical correlation, and association with other clinical features of RTT has been limited. For example, while the incidence of prolonged QTc in RTT varies widely in previous reports, no previous studies have looked at QTc variability, which is an important electrophysiological characteristic affecting both the incidence of prolonged QTc and risk of sudden death. Hypothesis: QTc in RTT has a greater variability than QTc in a healthy age-and-gender matched historical control. Methods: Retrospective chart review of RTT patients with serial electrocardiograms (ECGs) was performed. Each ECG was manually read by two pediatric cardiologists, and the QTc was calculated using Bazett’s formula. ECGs while a patient was given potentially QTc prolonging medications were excluded. Prolonged QTc was defined as ≥ 460 ms for pre-pubertal and ≥ 480 ms for post-pubertal females. QTc variability, defined as the difference of the maximum and minimum QTc, was calculated for each patient and compared to a healthy age-and-gender matched historical control. Results: A total of 30 RTT patients (all females) and 116 ECGs were included in the study. The mean QTc was 442 ms (383—534 ms).Patient age rage was from 1- 45 years. The mean intra-subject variability in QTc in our patient cohort was significantly greater than that of the control cohort (16.5 ms vs. 8.1 ms, P &lt; 0.001). Twenty-one patients (70%) had variability greater than 2 standard deviations of the control group. The mean inter-subject variability in QTc was 26.8 ms (1.4 - 42 ms). The incidence of prolonged QTc in our cohort was 60% (18/30). However, the incidence of persistent prolonged QTc was 7% (2/30). Conclusions: QTc in RTT has a significantly larger variability than that of healthy controls. Given this QTc variability over time and its assocaition with increased risks of sudden death, serial evaluation of not only QTc but also QTc variability and dispersion should be part of the routine cardiac evaluation of RTT patients.
Abstract 16715: Troponin I Levels Correlate With Cardiac Magnetic Resonance Late Gadolinium Enhancement and Native T1 Values in Duchenne Muscular Dystrophy Cardiomyopathy and Identify Early Disease Progression
Authors: Sonia Voleti, Laura Olivieri, Karin Hamann, Heather Gordish-Dressman, Christopher Spurney
Journal: Circulation (2018)

Introduction: Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Elevated troponin levels are observed in DMD and may vary with disease progression. We studied troponin levels in DMD related to myocardial fibrosis and native T1 measures. Methods: This is a prospective, cross-sectional, observational study of 30 DMD subjects measuring native T1 levels and late gadolinium enhancement (LGE) on cardiac MR imaging (CMR) correlated with temporally associated serum troponin I levels. Non-parametric analyses including Spearman correlations and Kruskal-Wallis test were performed between groups. P-values resulting from the pair-wise comparisons were adjusted for multiple comparisons using the Sidak method where appropriate. Results: There were 15 DMD subjects with no LGE (age 12±3 yo; EF% 60±5) and troponin I level of 0.05±0.08; 7 DMD subjects with mild LGE (age 17±5 yo, EF% 52±8) and troponin I level of 0.28±0.36; and 8 DMD subjects with moderate to severe LGE (age 16±6 yo; EF% 54±8) and troponin I level of 0.11±0.14. There was a statistically significant positive correlation between troponin I levels and MOLLI septal native T1 values (r2=0.173, p=0.02). Troponin I levels in DMD subjects with mild LGE were significantly increased compared to subjects with no LGE (p=0.02). MOLLI lateral native T1 levels were increased with moderate-severe LGE compared to mild and none (p&lt;0.01), but did not correlate with troponin levels. Conclusions: Serum biomarker troponin I levels were increased in DMD subjects with mild LGE and correlated with MOLLI septal native T1 values. Troponin I levels may be a useful minimally invasive outcome marker to monitor myocardial disease progression in DMD cardiomyopathy.
Abstract 16867: Comparison of Ductal Arteriosus Stent and Blalock-Taussig Shunt as Palliation for Neonates With Sole Source Ductal-Dependent Pulmonary Blood Flow: Results From the Congenital Catheterization Research Collaborative
Authors: Holly Bauser Heaton, Athar M Qureshi, Bryan H Goldstein, Andrew C Glatz, Ronald A Ligon, Ari Gartenberg, Varun Aggarwal, Courtney E McCracken, Michael S Kelleman, Christopher J Petit
Journal: Circulation (2018)

Introduction: Ductus arteriosus stenting (DAS) is an accepted method for securing pulmonary blood flow in cyanotic neonates. However, in neonates with pulmonary atresia and single source ductal-dependent pulmonary blood flow (SSPBF), DAS remains controversial. Published outcomes in this population are limited. We sought to evaluate outcomes in neonates with SSPBF pts, comparing DAS and surgical Blalock-Taussig shunt (BTS). Methods: Neonates with SSPBF who underwent DAS or BTS from four centers of the Congenital Catheterization Research Collaborative from January 2008 to December 2015 were retrospectively reviewed. Peri-procedural complications, reintervention prior to ultimate surgical repair, pulmonary artery (PA) diameter and interval growth were compared using available imaging studies. A propensity score was utilized to compare cohorts adjusted for differences in patient factors. Results: Forty patients with DAS and 157 patients with BTS were included. At palliation, the DAS and BTS cohorts had similar age, weight, and expected ultimate physiology. Rates of procedural complications following BTS and DAS were also similar. Following initial palliation, DAS patients were less likely to be treated with inotropes (p &lt;0.01) or diuretics (p = 0.046). Both groups had similar median lengths of hospital stay DAS 19 days (9-38), BTS 13 (10-23), p=0.19 and rates of unplanned reinterventions (17.5% of DAS and 21% in BTS, p= 0.62). Pre-palliation PA diameter was smaller (p=0.02), and PA symmetry was lower (p=0.02) in the DAS cohort. However, by time of definitive repair there was no difference in PA symmetry (0.80 in DAS cohort vs 0.82 in BTS cohort, p=0.64), in PA diameter (Nakata 161mm 2 /m 2 (137-166) in DAS vs 152mm 2 /m2 (94-227) in BTS, p=0.62) or in PA growth (change in Nakata 51mm 2 /m 2 (-21-61) in DAS vs 24mm 2 /m 2 (-28-131) in BTS, p=0.79). Rates of PA plasty and post-repair PA interventions did not differ between the cohorts. Conclusions: In neonates with SSPBF, DAS and BTS appear to have equivalent outcomes post-palliation and at time of subsequent surgical repair. Despite concerns about DAS in SSPBF, it appears to be a durable approach with unchanged PA growth compared to BTS.
Abstract 16759: Repair of Functional Mitral Regurgitation Restores Life Expectancy in Selected Patients Less Than 70 Years of Age
Authors: Vincent Chan, David Messika-Zeitoun, Marc Ruel, David Glineur, Elsayed Elmistekawy, Thierry Mesana
Journal: Circulation (2018)

Introduction: Functional mitral regurgitation (MR) is common and associated with significant morbidity and mortality. Notably, correction of functional MR has not been demonstrated to improve survival. We therefore evaluated outcomes following repair of functional MR utilizing prospective population data. Hypothesis: We hypothesized that correction of functional MR may be associated with a survival benefit in selected patients. Methods: Between 2001 and 2018, 1896 patients underwent complex mitral surgery at our institution, of which 168 underwent repair of functional MR in whom the etiology of MR was due to annular dilation in 37, leaflet tethering in 100 and mixed in 31. Mean patient age was 66.2±9.9 years and 66 (39%) were female. Concomitant coronary artery bypass grafting was performed in 79 (47%) with an average of 2.5 grafts per patient. The mean preoperative left ventricle (LV) ejection fraction was 38.3±11.4% and indexed LV end-systolic dimension, 25.1±5.4 mm/m 2 . Average clinical and echocardiographic follow up averaged 5.5±3.8 years. Results: Thirty-day mortality was 0.6%. Overall survival for the patients following repair of functional MR was 93.3±2.0% and 75.6±3.8% 1-, and 5-years after surgery. Not surprisingly, sensitivity analysis demonstrated that survival was influenced by age at operation (hazard ratio (HR) 1.05±0.02 per increasing year) and preoperative left ventricle (LV) class (HR 1.32±0.18 per increasing LV grade) (Both p&lt;0.05). For patients &lt;70 years of age and with a preoperative LVEF &gt;35%, 5- year survival was 92.3±7.4%, respectively. This compares to an expected 5- year survival of 99.1%, for age and gender matched Canadians (Figure). For patients &lt;70 and with a preoperative LVEF &gt;35%, 5-year freedom from recurrent MR ≥2+ was 81.3±9.8%. Conclusions: Repair of functional MR is associated with favorable early and intermediate term results in selected patients. Notably, for the subset of functional MR patients &lt;70 and with a LVEF&gt;35%, 5-year survival was comparable to age and gender matched patients from the general population.
Abstract 16659: Nogo-B Receptor is Required for the Recruitment of Vascular Smooth Muscle Cells to Developing Blood Vessels
Authors: Ujala Rana, Wenquan Hu, Zhi Fang, Zhong Liu, Baofeng Zhao, Qing R Miao
Journal: Circulation (2018)

The blood vessel maturation involves the coordination of two cell types - endothelial cells (EC) and vascular smooth muscle cells (VSMC). Hence, understanding of EC and VSMC migration is an essential step in developing new therapeutic approaches for diseases-associated with blood vessel maturation defects. PDGF plays a critical role in blood vessel maturation by promoting VSMC proliferation and migration via Ras signaling pathway. Although Nogo-B receptor (NgBR) was identified as a cell surface receptor special for the ligand Nogo-B, it acts as a scaffold protein requested for Ras translocation to the plasma membrane, which is a critical step for Ras activation by PDGF receptor and other receptor tyrosine kinases. NgBR is expressed in both EC and VSMC. Previous reports demonstrated the genetic deletion of NgBR in endothelial cells causes the embryonic lethality due to cerebrovascular defects in mice. Here, we further elucidate the roles of NgBR in regulating the recruitment of VSMC in the developing blood vessels. The genetic deletion of NgBR in VSMC also results in embryonic lethality due to impaired VSMC coverage on blood vessels and hemorrhage. Mechanistically, our data demonstrated that NgBR is required for PDGF-induced Ras signaling pathway and VSMC migration. Interestingly, we also appreciate the defects of VSMC recruitment in the blood vessels of NgBR EC-specific knockout mice. Gene profile analysis reveals that NgBR knockdown decreased the expression of PDGF in EC. Collectively, these data demonstrate that NgBR is an integral part of blood vessel maturation process by facilitating VSMC recruitment. Our results suggest that NgBR may be one of the essential genes coordinating the blood vessel development.
Abstract 16591: Exosome-Mediated Endothelial Cell Apoptosis and Network Disruption by Lymphangioleiomyomatosis-Smooth Muscle Cells (LAM-SMCs) Derived from Human Induced Pluripotent Stem Cell (iPSC)
Authors: Mirabelle S Ho, Miriel Ho, Lisa M Julian, William L Stanford, Duncan J Stewart
Journal: Circulation (2018)

Introduction: In LAM, SMC-like cells invade the lung thus compromising respiratory function which is dependent on normal vascular and alveoli structure. We posit that while healthy mural SMCs stabilize fragile neovessels and maintain vascular homeostasis, LAM-SMCs promote disruption of lung microvasculature by inducing endothelial cell (EC) apoptosis. Methods/Results: iPSCs derived from LAM patients or healthy subjects were differentiated into SMCs using a teratoma protocol. Co-culture of healthy iSMCs with HUVECs on Matrigel improved EC network persistence for ≥72Hrs, while LAM-SMC co-culture led to rapid network collapse in &lt;15Hrs. Culture of ECs with LAM-SMC conditioned media (24-72Hrs) increased EC apoptosis as assessed by Annexin V/PI flow cytometry, confirmed by increases in cleaved Caspase-3 protein expression. To further elucidate mechanism and kinetics of EC apoptosis, Annexin V/PI flow cytometry and Western Blot with Caspases 8,9,12 were performed in parallel at 3hr intervals from 0-12 Hrs. Increase in EC apoptosis at 9hrs, corresponded with a 6-fold increase in Cas-12 protein expression, followed by a 3-fold increase in Cas-9 at 12hrs with little change in Cas-8. This is in line with our RNAseq study showing dysregulation in endoplasmic reticulum and mitochondria related genes in LAM-SMC. Culture of HUVECs with LAM-SMC exosomes similarly induced EC apoptosis, with a profound decrease in EC gene expression (eNOS,TIE2,TAL1; 5-7 fold; p&lt;0.05) but increase expression of vessel-destabilizing, ANGPT2 (6-fold; p&lt;0.05). Scratch-wound assay also showed ~60% reduction (p&lt;0.05) in EC migratory capacity. Intriguingly, apoptotic ECs released exosomes containing translationally controlled tumor protein, TCTP, which were taken up by LAM-SMCs, as evidenced by immunofluorescence studies, associated with increases in the levels of proliferation-associated phospho-mTOR-and-S6k protein. Conclusions: LAM-SMCs derived exosomes resulted in EC apoptosis and network destabilization. Conversely, apoptotic ECs enhanced LAM-SMC growth, possibly by Caspase-dependent exosome release of TCTP, a positive regulator of mTOR signaling. These novel mechanisms may promote both microvasculature disruption and uncontrolled growth of LAM-SMCs.
Abstract 16872: Characterization of Pediatric Patients With Syndromic Anomalies Listed for Heart Transplant: Waitlist and Post-Heart Transplant Outcomes
Authors: Sarah J Wilkens, James R Priest, Beth Kaufman, Lynsey M Barkoff, David N Rosenthal, Seth A Hollander
Journal: Circulation (2018)

Introduction: We sought to describe the prevalence, characteristics and outcomes of pediatric patients with a syndromic anomaly (SA) who were accepted for listing for heart transplant (HT). Methods: This is a single center retrospective review of pediatric patients listed for heart transplantation after January 1, 2009 at our center. Patients were analyzed based on the presence of any underlying syndrome, which was heterogeneous and included chromosomal anomalies, skeletal myopathies, connective tissue disorders, mitochondrial disease and other systemic disorders. Waitlist and post-heart transplant outcomes were compared to those without SA. Results: A total of 243 patients were listed for (HT), of whom 21 patients (9%) had an associated SA (Table 1). Of those, 15 (71%) survived to transplant, 3 (14%) died while on the waitlist, 1 (5%) improved and was removed from the waitlist, and 2 (10%) patients are currently listed. Waitlist survival was not different between those with/without an associated syndrome (p = 1.0). Among those who survived to HT, there was no difference in median listing days (70 vs. 90 days, p=0.8), survival to hospital discharge [14 (93%) vs 150 (95%), p = 0.6], post-HT intubation days (2 vs 2 days, p = 0.6), or post-HT hospital length of stay (18 vs 18 days, p = 0.8). Overall survival was equivalent between groups post-HT, with a median follow-up time of 3.3 years (p = 0.7). Conclusions: A syndromic anomaly was present in 9% of pediatric patients waitlisted for heart transplant, but was not associated with an increased waitlist mortality, post-heart transplant hospital morbidity or long-term survival. If children with a syndromic anomaly were decided to be suitable candidates for heart transplant listing, they appear to have similar waitlist times and post-heart transplant survival as non-syndromic children.
Abstract 16806: Mechanisms of Sex Differences in Exercise Capacity
Authors: Marko Oydanich, Jie Zhang, Dorothey E Vatner, Stephen F Vatner
Journal: Circulation (2018)

The current policy for NIH grants involves rigor, which not only includes adequate statistics, but also examination of both males and females. The reason for the priority to examine sex differences is because male rodents have been used almost exclusively in pre-clinical studies, which allows for biases to arise. Accordingly, the goal of this investigation was to determine sex differences in exercise capacity in mice and the mechanisms mediating these differences. C57 female wild-type (WT) mice (5 months old) exhibited greater, p&lt;0.05, maximal exercise capacity for running distance (469 ± 24 m; n=7) than age-matched male WT mice (337 ± 14 m; n=8) as well as a 21% improvement in work to exhaustion. The first goal was to look at the effect of physical factors, such as weight and muscle mass, on exercise capacity. When matched for weight females still out-performed males in both running distance (541 ± 21 vs. 456 ± 18m, p&lt;0.05; n=10/group) and demonstrated an 18% improvement in work to exhaustion. Similar outcomes were observed when matching for hind-limb muscle mass. The second goal was to study the effects of estrogen on exercise capacity. After ovariectomy (OVX), female mice no longer demonstrated enhanced exercise compared with males. Conversely, chronic administration of estrogen to male mice improved capacity in running distance and work to exhaustion by 35% after 4 weeks of treatment. Next, we investigated nitric oxide (NO), a downstream target of estrogen, a mechanism which has not been examined previously for mediating sex differences in exercise capacity. Total NO synthase (NOS) activity was higher in female mice compared with male mice (207 ± 14 U/mg vs. 138 ± 4 U/mg, p&lt;0.05), but was no longer different after OVX. Furthermore, males chronically treated with estrogen exhibited a 47% increase in NOS activity. NO blockade with L-NAME eliminated the enhanced exercise capacity observed in both females and males treated with estrogen. Thus, as expected, estrogen is a key mechanism mediating the enhanced exercise capacity in female mice. However, this investigation also demonstrated another, novel key mechanism, increased nitric oxide activity.
Abstract 16702: Does Perceval Sutureless Aortic Valve Offer Advantages Over Traditional Surgical Aortic Valve Replacement?
Authors: Michael P Robich, Daniel J Gelb, Reed D Quinn, David Robaczewski, Dorothy Radziszewski, David J Malenka, Cathy S Ross, Alexander Iribarne, Anthony W DiScipio, Robert S Kramer
Journal: Circulation (2018)

Introduction: The Perceval S is a sutureless (SLV), rapid deployment, bovine pericardial aortic prosthesis on a nitinol stent. The role of this valve in the age of standard surgical and transcatheter aortic valve replacement is being defined. There are no data on cost from the United States. Methods: We performed a retrospective review of aortic valve replacement, comparing SLV with traditional sutured AVR (SAVR) at a single center between August 2015 and December 2017. Three surgeons who use both valve types performed 143 SLV and 117 SAVR procedures. Exclusions included mechanical valves, homografts, endocarditis, aortic dissection or emergency status. Hospital cost data (including valve cost) were reviewed. Inverse probability weighting (IPW) was used to balance the groups. Results: Compared to SAVR, SLV patients were significantly older (Table). Additional procedures (i.e., CABG) were performed with equal frequency. Minimally invasive access was more common for SLV. Cross clamp times were significantly shorter for SLV than SAVR, but were comparable when other procedures were performed. After IPW, groups were well balanced. SLV patients had higher rates of permanent pacemaker placement, pleural effusions and a greater post-procedure drop in platelet counts. There were no differences in rates of postoperative transfusions, atrial fibrillation, stroke, renal failure, prolonged ventilation, length of stay or in-hospital mortality. Hospital costs were comparable. Pacemaker rates for SLV decreased over time (25% in 2015 to 4% in 2017, Ptrend =.003). Conclusion: SLVs were selectively used in an older population and were associated with shorter cross clamps times. They were not associated with an increased risk of adverse events other than pacemaker placement, for which there was a learning curve and despite this, their associated cost of care was not significantly great than for SAVR. This valve may be advantageous in older, higher risk patients requiring concomitant operations.