tbuckley/cabot-search huggingface dataset:
Abstract 12780: Impact of Atrial Fibrillation on Exercise Intolerance in Patients With Preserved Left Ventricular Ejection Fraction
Authors: Toshihiko Goto, Marina Ishida, Shohei Kikuchi, Kazuaki Wakami, Kento Mori, Hidekatsu Fukuta, Nobuyuki Ohte
Journal: Circulation (2016)

Introduction: When atrial fibrillation (AF) develops, there is loss of the atrial kick, with consequent decrease of cardiac output. Therefore, AF is recognized as an exacerbating factor for heart failure in patients with heart disease. However, the relationship between permanent AF and exercise intolerance in this population has been incompletely understood. Accordingly, we examined whether the presence of AF exacerbates exercise tolerance in patients with preserved left ventricular ejection fraction (LVEF). Methods: We studied 402 patients (age 68.0±9.6 years; male 67.5%) with 370 in sinus rhythm (SR) and with 32 in permanent AF. All patients had preserved LVEF (&gt;50%) and were 40 years old or more. Patients underwent cardio-pulmonary exercise testing (CPX) including an analysis for oxygen uptake at peak exercise (peak VO 2 ). Before CPX, comprehensive Doppler echocardiography was carried out. Early diastolic transmitral velocity (E) and mitral annular velocity during early diastole (e’) were measured. Results: No significant difference was found in age, body mass index, or the E/e’ ratio (9.0±3.2vs9.9±3.8, p=0.12) between the patients with SR and those with AF. Patients with SR had significantly higher LVEF (70.9±7.9vs66.2±8.7%, p=0.001) and higher proportion of female gender (34.9vs6.3%, p=0.001) than in those who with AF. Peak VO 2 did not differ between patients with AF and those with SR (19.2±5.2vs20.4±5.8ml/kg/min, p=0.28). In multiple logistic regression analysis, age (OR 3.7, 95%CI2.4-5.9, p&lt;0.001) and female gender (OR 4.0, 95%CI 2.4-6.7, p&lt;0.001) significantly contributed to exercise intolerance. However, the presence of AF (p=0.12) and higher LVEF (p=0.45) were not selected. Conclusions: Similar exercise tolerance was observed between patients with SR and those with permanent AF. These data suggest that permanent AF does not affect the exercise intolerance in patients with preserved LVEF.
Abstract 12791: Heart Rate at One Minute Impact Neonatal Resuscitation &amp; Clinical Outcomes in Infants
Authors: Vasantha H Kumar, Annie Skrobacz, Changxing Ma
Journal: Circulation (2016)

Introduction: Fetal hypoxia from intrapartum events can lead to absent heart rate (HR) or bradycardia (BC) at birth requiring neonatal resuscitation. Neonatal resuscitation guidelines do not differentiate infants with BC (HR&lt;100/min) from absent HR at birth; Hypothesis: As HR is the primary determinant of resuscitation, we hypothesize that infants with no HR at 1min [determined by Apgar score (AS) of 0 @ 1min] would require more extensive resuscitation with worse clinical outcomes compared to infants with BC at 1min (determined by AS=1 @ 1 min). Methods: A retrospective analysis was done on infants born from 1/1/00 - 12/31/15 with AS of 0 (ASZ grp) or AS of 1 (ASN grp) at 1min. Patient demographics, resuscitation characteristics &amp; clinical outcomes were analyzed in both the groups. Descriptive statistics &amp; logistic procedure was performed (SAS System, Cary, NC). Results: Table.1 summarizes the resuscitation characteristics analyzed. AS were different between the groups over time (Fig.1). Death was higher in ASZ grp compared to ASN grp [0.37 (0.18-0.77)] &amp; at lower gestational ages (GA) [0.82 (0.76-0.89)]. Infants who died had lower AS at 5 min [0.67 (0.55-0.82)]. Infants &lt; 32 wks GA had higher incidence of PDA &amp; severe IVH in the ASZ grp. Conclusions: Infants with no HR at 1min did worse than infants with BC. Death &amp; low AS may reflect the severity of illness at birth, particularly in premature infants with no HR. Current guidelines do not address management of infants with HR of zero at birth. NRP need to include an algorithm for a subset of infants with absent HR at birth, as prompt resuscitation may decrease mortality &amp; improve clinical outcomes of these infants.
Abstract 12677: Long-Term Survival of Patients With Left Bundle Branch Block who are Clinical or Echocardiographic Hypo-Responders to Cardiac Resynchronization Therapy
Authors: Himabindu Vidula, Valentina Kutyifa, Scott McNitt, Ilan Goldenberg, Scott Solomon, Arthur J Moss, Wojciech Zareba
Journal: Circulation (2015)

Introduction: Guidelines support cardiac resynchronization therapy with a defibrillator (CRT-D) in heart failure (HF) patients with left bundle branch block (LBBB). However, not all patients demonstrate clinical or echocardiographic (ECHO) response to CRT-D. We aimed to compare the long-term outcomes of clinical hypo-responders and ECHO hypo-responders with LBBB who were enrolled in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT). Methods: Five-hundred thirty-four patients with LBBB in the CRT-D arm were followed for 5.6 years (median). Clinical hypo-response was defined as presence of defibrillator treated ventricular arrhythmia or HF event in the first year after CRT-D implantation. ECHO hypo-response was defined as less than or equal to 35% reduction (median) in left ventricular end-systolic volume (LVESV) 1 year after CRT-D implantation; we also tested 15% and 25% reduction in LVESV. Results: Clinical and ECHO response was observed in 246 (46%) patients. Two-hundred twenty-six (42%) patients were ECHO hypo-responders and 62 (12%) patients were clinical hypo-responders. Fifty (9%) patients died during long-term follow-up. ECHO hypo-responders had an increased risk of all-cause mortality compared to clinical + ECHO responders (hazard ratio [HR] 3.02, 95% CI 1.45-6.31, p=0.003). Clinical hypo-responders had an increased risk of mortality compared to clinical + ECHO responders (HR 3.67, 95% CI 1.45-9.33, p=0.006), but not compared to ECHO hypo-responders. There was no significant difference between outcomes for clinical hypo-responders and ECHO hypo-responders when using an ECHO cutoff of 15% or 25% reduction in LVESV. Conclusion: During long-term follow-up, heart failure patients with LBBB who have clinical or echocardiographic hypo-response to CRT-D have comparable increased risk of mortality relative to patients who demonstrate good clinical and echocardiographic responses.
Abstract 13085: Isolated Tricuspid Valve Surgery: Failure of Its Principle? Long-Term Outcome Analysis
Authors: Gianluca Lucchese, Ian Cummings, Lionel Oo, James Roxburgh, Vassilios Avlonitis
Journal: Circulation (2015)

Introduction: Isolated tricuspid valve (TV) surgery for acquired TV disease is high-risk surgery and the decision to operate is still controversial. We describe a single-centre experience with isolated TV surgery and our long-term analysis for adverse outcome. Methods: A retrospective analysis of 62 consecutive patients who underwent isolated TV surgery for acquired TV disease between 2002 and 2014 has been performed. Associated cardiac procedures and congenital TV disease were exclusion criteria. The Kaplan-Meier, Univariate and Cox regression analysis were respectively used to evaluate mortality and identify risk factors at long-term follow-up. The Duke Activity Status Index (DASI) questionnaire, to measure the functional status related to daily living, has been used to assess the survivors’ quality of life. Results: Mean patient age was 60.2±18.9 years, 38% were male and the average log EuroSCORE was 16.8%±15.9%. TV repair was performed in 38 cases (61%), replacement in the remainder and 38% were reoperations. 30-day mortality was 15% (n=9) , similar for repair and replacement. Follow-up (median=35.7 months, range=0.1-150) was 100% complete. Survival at 1, 5 and 10 years was 79.5%±5%, 69.8%±6% and 53.5%±9.7% respectively. Sinus rhythm, NYHA class &lt; III, age &lt; 60 years were identified as independent predictors of survival at long-term follow-up. Furthermore, we found that survivors with a lower pre-operative NYHA functional class were also those with the best quality of life at follow-up (DASI score 20.5 ± 8.6 vs 12.7 ± 7, p=0.028). Conclusions: Patients who undergo isolated TV surgery continue to be a high-risk group in with high early and late mortality. There is no difference in mortality between TV repair and replacement at long-term follow-up. Our experience suggests that a shift towards earlier surgery may be proven to confer an advantage, as surgery before the onset of NYHA class 3 symptoms is associated with improved outcome and better quality of life.
Abstract 12625: Splenic Leukocytes Defines the Resolution of Inflammation and Left Ventricle Healing in Heart Failure Pathology
Authors: Ganesh V Halade, Iliyan Vlasakov, Vasundhara Kain, Paul Norris, Charles N Serhan, Kevin A Ingle
Journal: Circulation (2016)

Introduction: After myocardial infarction (MI) self-healing is prominent in mice but not in humans. MI-induced innate inflammatory and resolving response is unclear in left ventricle (LV) healing. Hypothesis: To define innate and resolving response, our aim was to quantitate time-dependent generation of specialized pro-resolving mediators (SPMs) and leukocyte trafficking in the LV and spleen post-MI. Methods: We determined the leukocyte kinetics by flow cytometry and quantitated resolution metabolome using mass spectrometry in C57BL/6 mice after permanent coronary ligation. Results: Lipid Mediator metabololipidomic analyses revealed that spleen not only serves as a leukocyte reservoir but it also participates actively in SPMs production post-MI. Post-MI leukocyte (CD11b + Ly6G + CD206 + ) turnover at d1 linked to increased SPMs levels in the infarcted LV with marked increase of resolvin (Rv)D1, RvD3-6, maresin (MaR)1, lipoxins (LX) and protectin D1 compared to d0 naïve controls and d5 post-MI. Before MI, SPMs such as RvD5, RvD6, protectin (PD)1, AT-PD1, MaR1, LXA 4 , AT-LXA 4 , AT-LXB 4 , were higher in spleen than LV indicating that splenic leukocytes mobilize SPMs to activate the healing program in LV post-MI. Lipoxygenase (LOX -5, -12 and -15) were preferentially activated in LV, while cyclooxygenase (COX-1 and -2) in the spleen post-MI. MI-induced comprehensive leukocyte analyses provided the self-regulating means of pro-inflammatory and resolving neutrophils (CD11b + Ly6G + CD206 + ) and macrophages (CD11b + Ly6C hi CD206 + ) in a time dependent manner in the infarcted LV but to a lesser extent in the spleen. Thus, the splenic storage of SPMs, generation of increase LOX-mediated SPMs in the infarcted LV and COX-mediated prostanoids in the spleen facilitates the MI-induced murine LV healing post-MI. Conclusions: The abundance of SPMs in the spleen before MI and amplified SPMs generation in the infarcted LV within 24 hours post-MI confirms that splenic leukocytes determine the murine self-healing post-MI. Thus, the acute phase coincides with the resolving response post-MI and demands investigation of the SPMs role in heart failure pathology.
Abstract 12560: Effect of Somah Solution on Hypoxia/Reoxygenation Induced Coronary Artery Endothelial Injury: A Comparison to Current Ex-Vivo Heart Perfusates
Authors: Roberto V Ribeiro, Hiroyuki Kawajiri, Arash Ghashghai, David Banner, Mitesh V Badiwala, Vivek Rao
Journal: Circulation (2016)

Introduction: Ex-Vivo Heart Perfusion (EVHP) has been proposed to expand cardiac donation by enabling resuscitation and preservation of hearts donated after circulatory death. Hypoxia/reoxygenation endothelial injury affects organ viability and patient’s outcomes. STEEN Solution is accepted as the primary component for perfusion of other solid organs. However, there is lack of evidence to determine the optimal perfusate composition to maintain cardiac viability during longer periods of perfusion. Somah solution has been proposed as a novel cardioprotective solution optimized to meet cardiac metabolism and confer enhanced protective effects against reperfusion injury. Our aim was to compare the effects of STEEN and Somah on endothelial reoxygenation injury in vitro. Methods: Human coronary artery endothelial cells were exposed to 16 hours of hypoxia in culture medium followed by 16 hours of reoxygenation treated with Celsior, STEEN or Somah to simulate the EVHP setting. Endothelial activation markers’ gene expression was assessed through qRT-PCR; supernatant was collected to quantify endothelin-1 (ET-1) with ELISA; and quantitative neutrophil adhesion assay was performed to evaluate endothelial function. Results: Treatment with Somah demonstrated decreased expression of cell surface adhesion molecules E-Selectin (Me 0.133±0.12, So -0.073±0.34, ST 1.624±0.46, Ce 0.999±0.45 fold-change from hypoxia; p=0.002) and VCAM-1 (Me -0.004±0.20, So -0.363±0.43, ST 0.428±0.39, Ce 0.597±0.13 fold-change from hypoxia; p=0.023), and vasoactive molecule MCP-1 (Me 0.225±0.72, So -0.510±0.70, ST 1.500±0.49, Ce 0.829±0.28 fold-change from hypoxia; p=0.015). Celsior and Somah reduced cell secretion of ET-1 (Me 395 pg/ml, So 20 pg/ml, ST 448 pg/ml, Ce 16 pg/ml; n=4, p&lt;0.05). Reoxygenation injury increased neutrophil adhesion to endothelial cells; there was a non-statistically significant trend towards protection against this injury with Somah. Conclusions: Somah exerts protective effect against reoxygenation injury when compared to STEEN in vitro. It may have utility in enhancing cardiac organ preservation during EVHP. Future studies in a pre-clinical setting should be conducted to address this question.
Abstract 12743: Risk of Cardiovascular Readmission Within 3 Years Following a Hypertensive Complication of Pregnancy
Authors: Jennifer L Jarvie, David P Kao
Journal: Circulation (2016)

Introduction: Women with pregnancies complicated by pregnancy-induced hypertension (PIH) have increased cardiovascular (CV) risk decades later. We sought to determine if these women demonstrate greater CV risk more immediately. Methods: Using administrative data, we extracted all hospital-based deliveries in the state of Florida from 2004 through 2013. Deliveries and clinical diagnoses were determined using ICD-9 CM codes. Readmissions to any Florida hospital were identified using unique patient identifiers. Our primary predictor was PIH, defined as a composite of gestational hypertension, pre-eclampsia, and eclampsia. Outcomes of interest were CV readmission, defined as a composite of myocardial infarction, stroke, or heart failure; non-CV readmission, and no readmission within 3 years of index delivery. Clinical profiles and maternal outcomes were stratified by readmission status. The association between risk of readmission and PIH was determined using logistic regression. Results: A total of 1,834,166 records from delivering mothers were included (mean age 27.3 ± 6.2 years; 53% white, 25% African American [AA], 20% Hispanic). There were 4,732 CV readmissions and 321,713 non-CV readmissions within 3 years of index delivery. When stratified by readmission status, there was a higher make-up of women with PIH in the CV readmission group compared with the other groups (16.5% CV readmission, 9.3% non-CV readmission, 7.4% no readmission; p&lt;0.001) and a higher rate of obesity (13% CV readmission, 5% non-CV readmission, 3% no readmission; p&lt;0.001). Sixty percent of women in the CV readmission group were AA. Women with PIH had a higher multivariate risk of both CV readmission (OR 1.71; 95% CI 1.48 - 1.86) and non-CV readmission (OR 1.08; 95% CI 1.07 - 1.10). Compared with white women, AA women had the highest risk for CV readmission (OR 3.39; 95% CI 3.17 - 3.63) and Hispanic women had the lowest risk of CV readmission (OR 0.60; 95% CI 0.53 - 0.67) after adjustment for PIH. Conclusion: In this diverse sample, women with PIH have a higher risk of CV readmission within 3 years of delivery. Significant racial and ethnic differences were seen in the risk for CV readmission among women with pregnancies complicated by PIH with a markedly higher risk in AA women.
Abstract 18617: Is Genetic Hypertension Immunologically Mediated and Adoptively Transferrable by Bone Marrow From the Spontaneously Hypertensive Rat?
Authors: Madhu V Singh, Michael Z Cicha, Carol A Whiteis, Mark W Chapleau, Nicholas Zavazava, Francois M Abboud
Journal: Circulation (2013)

We have recently reported that a proinflammatory state of the innate immune system may contribute to genetic hypertension in the spontaneously hypertensive rat (SHR). In these experiments we contrasted the population of immune cells from SHR and from the normotensive control WKY, and tested the hypothesis that the hematopoietic system of SHR is prohypertensive when adoptively transferred to a normotensive F1 hybrid (WKY x SHR) rat. We performed immuno-phenotyping of splenocytes from the day of birth to 38 weeks. A specific subset of CD161+ splenocytes, which was sparsely seen in WKY (&lt;1%) at any age, was increased at birth in SHR to a level of 5% and progressively increased to 10, 20 and 30% at 5, 20, and 38 weeks of age respectively. CD161+ cells are characteristically Th17 cells, NK cells, and dendritic cells that overexpress retinoic acid related orphan receptor gamma (RORγt) and IL-17, a pro-inflammatory prohypertensive cytokine. We also transfused bone marrow from 5-week-old male WKY or SHR into 5-week-old F1 hybrid rats (WKY x SHR) that had been sub-lethally irradiated (9-12 Gy). Blood pressure (tail cuff) of the recipient F1 rats was measured after transplantation. Early results indicate that at 2, 5 and 7 weeks after transfer, the systolic pressure averaged 140±2, 152±8, and 150±5 mmHg (n=4) in F1 recipients of WKY marrow, respectively. Corresponding values in F1 recipients of SHR marrow were 150±5, 158±5, and 169±6 mm Hg (n=4). We conclude that 1) SHR exhibit a much higher abundance of proinflammatory CD161+ immune cells than WKY beginning prior to the onset of hypertension and progressively increasing with age, and 2) Preliminary results suggest that genetic hypertension may be adoptively transferred with bone marrow from SHR and not WKY rats.
Abstract 13240: Soluble Flt-1 Deficiency is One of the Mechanisms of Cardiac Hypertrophy and Heart Failure in CKD Through Up-regulation of MCP-1
Authors: Ayako Seno, Yukiji Takeda, Masaru Matsui, Yasuki Nakada, Tomoya Ueda, Takaki Matsumoto, Aya Okuda, Bart Jonckx, Hitoshi Nakagawa, Kenji Onoue, Makoto Watanabe, Hiroyuki Kawata, Rika Kawakami, Shiro Uemura, Yoshihiko Saito
Journal: Circulation (2015)

Background: Uremic cardiomyopathy is responsible for high morbidity and mortality in patients with chronic kidney disease (CKD), which is characterized by cardiac hypertrophy and heart failure. But precise mechanisms are still unknown. In our previous data, soluble Flt-1 (sFlt-1), which is an endogenous inhibitor of PLGF (placental growth factor), is a key molecule of cardiovascular disease in CKD. Soluble Flt-1 production was decreased with the progression of renal diseases, and sFlt-1 deficiency resulted in progression of cardiac hypertrophy and heart failure, which was revealed by using sFlt-1 KO mice (sFlt-1 -/- ). In this study, we examined the novel mechanisms of heart failure and cardiac hypertrophy using sFlt-1 -/- mice which mimic the CKD condition. Methods and Results: We performed transverse aortic constriction (TAC) in sFlt-1 -/- and WT, and evaluated after 7 days. LV wall thickening was significantly increased and ejection fraction was decreased in sFlt-1 -/- compared to WT by echocardiography. Histological analysis showed that myocardial fibrosis and macrophage infiltration were significantly increased in sFlt-1 KO compared to WT. Anti-PLGF neutralizing antibody (αPLGF: ThromboGenics, Heverlee, Belgium) prevented pressure-overloaded cardiac hypertrophy and cardiac dysfunction after TAC in sFlt-1 -/- . In addition, MCP-1 expression was increased in the hearts of sFlt-1 -/- compared to WT after TAC. Echocardiographic analysis showed that inhibition of MCP-1 with neutralizing antibody prevented cardiac hypertrophy and systolic dysfunction in sFlt-1 -/- , which implied that MCP-1 was one of the key chemokines for the progression of heart failure in sFlt-1 deficiency. Human cardiac biopsy samples revealed that macrophage mobilization, fibrosis, and MCP-1 expression were increased in uremic cardiomyopathy, which was quite similar to sFlt-1 -/- . Conclusions: The present study demonstrated that PLGF activation in CKD by decrement of sFlt-1 induced macrophage activation and MCP-1 up-regulation which led to cardiac hypertrophy and heart failure. PLGF and MCP-1 are novel mechanisms and therapeutic target of cardiac hypertrophy and heart failure in CKD.
Abstract 18573: Genetic Variation of the Alpha-Subunit of the Epithelial Sodium Channel Influences the Lung Fluid Response to Hypoxia in Healthy Humans
Authors: Sarah Baker, Courtney Wheatley, Bryan Taylor, Manda Keller, Bruce Johnson, Eric M Snyder
Journal: Circulation (2013)

Cardiogenic pulmonary edema is a life-threatening complication in patients with heart failure (HF) resulting from increased alveolar Cl- secretion and inhibition of alveolar epithelial Na+ channels (ENaC). Not all HF patients develop pulmonary edema, despite similar clinical characteristics, suggesting a genetic component to edema formation in response to cardiac failure. The ENaC are crucial for alveolar fluid clearance, with the alpha subunit demonstrating particular importance. We have previously found that genetic variation of the alpha subunit (SCNN1A) of ENaC, an alanine (A) to threonine (T) substitution, influences ion regulation during exercise and in response to albuterol. In the present study, we sought to determine the influence of the threonine variant (T663; AT/TT group) on lung fluid regulation in response to normobaric hypoxia, an environmental condition known to increase pulmonary capillary hydrostatic stress in healthy humans. Lung ion and fluid changes were assessed using exhaled Na+ (ENa+) and the lung diffusing capacity for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) to determine alveolar-capillary membrane conductance (DM). 19 healthy subjects (n=8 vs. 11, %female=50 vs. 62%, age=27±1 vs. 28±2yrs., ht=171±3 vs. 173±2cm, wt=69±6 vs.72±3kg , BMI=23±1 vs.24±1kg/m2 , for AA and AT/TT, respectively) completed two overnight visits in a hypoxic tent simulating just over 5,400m. The visits were randomized to inhaled placebo (P) or inhaled amiloride (Aml, 1.5mg in 5ml normal saline, used to inhibit ENaC activity) with ENa+, DLCO, and DM assessed at baseline and following 12 hours of hypoxic exposure. There was an effect of genotype on the ENa+ response to hypoxia with placebo that was abolished with amiloride, but no effect of genotype on the diffusing capacity of the lung (Table). These results suggest that genetic variation of SCNN1A may influence ion regulation in the lung under conditions of elevated hydrostatic stress.