tbuckley/cabot-search huggingface dataset:
Abstract 18404: Warfarin Persistence in Atrial Fibrillation: The Michigan Anticoagulation Quality Improvement Initiative Experience
Authors: Alexis Lopez, Geoff D Barnes, Xiaokui Gu, Brian Haymart, Eva Kline-Rogers, Steve Almany, Jay Kozlowski, Dennis Besley, Syed Ahsan, Gregory D Krol, Scott Kaatz, James B Froehlich
Journal: Circulation (2013)

Introduction: Warfarin reduces the risk of stroke in patients with atrial fibrillation (AF), but increases the risk of bleeding. In clinical trials, persistence with warfarin therapy ranges from 75-79% at one year, but few studies offer real-world estimates of warfarin persistence. There is limited data demonstrating the relationship between CHADS2 and HAS-BLED scores with adherence to warfarin. Methods: New patients treated with warfarin for stroke prevention in AF were followed at seven anticoagulation clinics involved in the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) collaborative. Patients were excluded if they had additional indications for warfarin such as artificial valve, DVT, or PE. Risk factors for CHADS2 and HAS-BLED scores and reasons for warfarin discontinuation were abstracted from patient charts. Kaplan-Meier (KM) curves were constructed to characterize drug therapy discontinuation rates at one year. Cox proportional hazard regression and logistic regression analyses were performed to assess the effects on warfarin persistence by CHADS2 and HAS-BLED scores. Results: Of 1,973 eligible patients, 153 (7.8%) switched to non-warfarin therapy (e.g. dabigatran). In the remaining 1820 patients, one year persistence is 63% based on KM estimates. One year persistence by low, intermediate, or high CHADS2 score was 29%, 58%, and 73%, respectively. One year persistence for low, intermediate, or high HAS-BLED score was 41%, 66% and 76%, respectively. Warfarin persistence at one year was associated with an increasing CHADS2 (OR 1.244, CI 1.045-1.482) but not associated with HAS-BLED score (OR 1.016, CI 0.839-1.231) in multivariate analysis. Conclusions: A significant proportion of patients taking warfarin for SPAF discontinue therapy by one year. In the multivariate analysis, patients at higher risk of stroke, but not bleeding, are more likely to remain on warfarin therapy. Efforts to improve warfarin persistence need further investigation.
Abstract 13185: Association Between Bariatric Surgery and Emergency Department Visits and Hospitalizations for Atrial Fibrillation
Authors: Yuichi J Shimada, Yusuke Tsugawa, Kohei Hasegawa
Journal: Circulation (2015)

Introduction: Atrial fibrillation (AF) carries a large societal burden. Although studies suggested reduction of AF-related symptoms after bariatric surgery, little is known about whether bariatric surgery affects harder clinical endpoints related to AF. Hypothesis: Bariatric surgery is associated with a reduction in the rate of ED visits and hospitalizations for AF. Methods: We performed a self-controlled case series study of obese patients with AF who underwent bariatric surgery, using the population-based ED and inpatient sample in 3 states (California, Florida, and Nebraska). Primary outcome was ED visit or hospitalization for AF from 2005 to 2011. We used conditional logistic regression to compare each patient's rate of the outcome event during sequential 12-month periods, using pre-surgery months 13-24 as the reference period. Results: We identified 1056 patients with AF who underwent bariatric surgery. During the reference period, 12.1% (95%CI, 10.1-14.0%) of patients had an ED visit or hospitalization for AF (Figure). The rate remained unchanged in the subsequent 12-month pre-surgery period (12.6%; 95%CI, 10.1-14.6%) with adjusted odds ratio [aOR] of 1.05 (95%CI, 0.81-1.36; P=0.74) compared to the reference period. In the first 12-month post-surgery period , we observed a similar rate of ED visits or hospitalizations for AF (14.2%; 95%CI, 12.1-16.3%), corresponding to aOR of 1.20 (95%CI, 0.93-1.55; P=0.16). The rate remained stable in the subsequent 13-24 months after bariatric surgery (13.4%; 95%CI, 11.3-15.4%), corresponding to aOR of 1.12 (95%CI, 0.87-1.45; P=0.40). Conclusions: Our findings indicate that bariatric surgery is not associated with lower rates of AF episodes requiring ED evaluation or hospitalization among obese patients with AF. Our data facilitate further investigations to fill the gap between symptom improvement and lack of reduction in healthcare utilization in the high risk population with AF.
Abstract 18389: Apamin Sensitive Current (IKCa ) Modulates Ventricular (but Not Atrial) Repolarization in Human Heart Failure
Authors: Ingrid M Bonilla, Victor P Long, Patrick Wright, Paul M Janssen, Philip Binkley, Peter J Mohler, Cynthia A Carnes
Journal: Circulation (2013)

Altered myocyte electrophysiology in heart failure contributes to cardiac arrhythmias. In chronic human heart failure atrial repolarization is shortened while ventricular repolarization is prolonged. The calcium activated potassium (I KCa ) current has been suggested as a novel atrial-selective pharmacologic target to modulate repolarization and arrhythmogenesis. We hypothesized that chamber-specific differences in I KCa current contribute to HF-induced repolarization changes. Methods: End-stage failing hearts obtained at the time of transplant were used to isolate left ventricular (LV) midwall and left atrial appendage (LAA) myocytes. Action potential durations (APDs) were recorded at 0.5, 1 and 2 Hz before and after the application of 100nM apamin, an I KCa blocker. Results: In LAA cells, apamin had no effect on APD50 or APD90 and no cellular arrhythmias (i.e. early afterdepolarizations, EADs) were observed. In the ventricular cells, apamin resulted in significant prolongation of the APD50 (p&lt;0.05) and APD90 (p&lt;0.05) at all rates; there was also a 40% increase in EADs, consistent with proarrhythmic potential. Conclusions: In end-stage human HF, I KCa modulates LV repolarization and I KCa inhibition induces cellular arrhythmias. I KCa does not appear to modulate LAA myocyte electrophysiology in end-stage HF; our results do not support I KCa as a pharmacologic target for AF associated with heart failure. Potential explanations for the chamber-specific effects we observed include differential HF-induced alterations in APD, channel expression or calcium cycling. Thus, we suggest that inhibition of I KCa as a pharmacologic strategy in HF may be detrimental, as it may favor the initiation of triggered ventricular arrhythmias.
Abstract 18290: Mitochondrial-Targeted Overexpression of Transcriptionally Inactive STAT3 in the Heart Reduces Infarct Size and Improves Contractile Recovery Following Ischemia and Reperfusion
Authors: Karol Szczepanek, Aijun Xu, Ying Hu, Qun Chen, Edward J Lesnefsky
Journal: Circulation (2013)

Signal Transducer and Activator of Transcription 3 (STAT3) is a transcription factor that drives expression of antiapoptotic and antioxidant genes. STAT3 contributes a crucial role in protection against ischemia (ISC)-reperfusion (REP) injury. STAT3 is also found in the mitochondria, where it modulates the activity of the electron transport chain (ETC) and the permeability transition pore. We have previously shown that transgenic mice overexpressing mitochondrial-targeted, transcriptionally inactive STAT3 in cardiomyocytes (MLS-STAT3E mice) exhibit a persistent, partial blockade of electron transfer through complex I that uniquely does not lead to tissue dysfunction at baseline yet increases mitochondrial ischemic tolerance. MLS-STAT3E protects complex I against ischemic damage, attenuates reactive oxygen species (ROS) production from the ETC and inhibits cytochrome c release during ISC. The direct contribution of non-transcriptional, mitochondria-localized STAT3 to protection during ISC-REP remains to be established. We hypothesize that the enhanced mitochondrial tolerance seen in MLS-STAT3E mice will decrease cardiac injury during ISC-REP. In the isolated buffer-perfused heart model of ISC-REP, non-transgenic littermate (WT) hearts subjected to 35 min of ISC and 60 min of REP exhibit an infarct size of 34 ± 2% (n=10) of the left ventricle (LV) risk area. MLS-STAT3E hearts are more resistant to ISC-REP injury with a decreased infarct size (23 ± 5%; P&lt;0.05, n=10). Contractile recovery, expressed as a percent of LV developed pressure before ISC, is improved in MLS-STAT3E mice compared to WT (10 ± 2% WT vs. 21 ± 3% MLS-STAT3E; P&lt;0.05, n=10). Mitochondria isolated after ISC-REP show MLS-STAT3E-mediated attenuation of ROS release. These results suggest that the partial and persistent blockade of complex I present in MLS-STAT3E decreases ISC-REP injury. Our data implicates STAT3 as a mediator of cardioprotection not only via canonical action as a transcription factor, but also as a modulator of ETC activity directly in the mitochondria.
Abstract 18457: Outpatient Milrinone Therapy as a Bridge to Pediatric Heart Transplantation: A Large Single Center Experience
Authors: Scott R Auerbach, Jean Cavanaugh, Biagio Pietra, Shelley D Miyamoto
Journal: Circulation (2013)

Objective: Milrinone infusion as treatment of end stage heart failure in children is well established. Previous reports of outpatient milrinone therapy (tx) are limited by small numbers. Our objective was to evaluate the safety of outpatient milrinone tx as a bridge to heart transplant (HT). Methods: We retrospectively reviewed the records of all patients (pt) at our institution that have received outpatient milrinone tx between February 2000 and June 2013. Results: A total of 53 pt received outpatient milrinone tx, all had failed milrinone weaning, all began milrinone as an inpatient, and all had an indication of bridge to HT. The median age was 9.7 years [IQR 2-16] and 27 (51%) were male. The diagnosis prior to HT was congenital heart disease (15), cardiomyopathy (21; 16 dilated and 5 restrictive), and graft failure (17). Successful HT was performed in 52 and 1 pt is alive waiting. The median length of stay (LOS) for initiation of milrinone was 7 days (d) [IQR 2-16]. There were 2737 d of outpatient milrinone tx without a death and the median duration of tx was 28 d [IQR 15-62; range1-377]. The mean dose was 0.5 ± 0.02 mcg/kg/min. Arrhythmias occurred in 2 pt (atrial flutter and 3 beats of non-sustained ventricular tachycardia). There were 27 rehospitalizations in 16 pt for a total 97 inpatient days with a median LOS of 2d [IQR 1-3]. Indications for rehospitalization were atrial flutter (1pt, 3d),worsening heart failure (4pt, 26d, median LOS=3d [IQR 1-11]), central venous line (CVL) malfunction (10 pt, 23d, median LOS = 1d [IQR 1-2], CVL infection (2 pt, 5d, mean LOS = 2.5d +/- 0.71, and other (16pt,10 admissions, 40d, median LOS=2d [IQR 1-6]. One pt with worsening heart failure was admitted for additional inotropic support with dopamine and remained an inpatient until HT. Conclusion: There was no mortality in patients on milrinone awaiting HT. Arrhythmias were rare and catheter related complications were infrequent. The outpatient use of milrinone in children is safe and effective when initiated in the inpatient setting and it may reduce costs and improve quality of life in children awaiting HT.
Abstract 18477: Left Ventricular Ejection Fraction is Not Sensitive Enough to Accurately Determine Timing of Surgical Referral for Asymptomatic Patients With Chronic Mitral Regurgitation
Authors: Hersh S Maniar, Beckah D Brady, Urvi Lee, Brian P Cupps, Julia Kar, Michael K Pasque
Journal: Circulation (2013)

The current clinical guidelines for asymptomatic patients with chronic MR, utilize EF to trigger surgical referral. We hypothesize that 1) EF is not sensitive enough to detect the earliest contractile injury in chronic MR and 2) injury associated with chronic MR is not global but rather heterogeneous, occurring regionally and predictably, and prior to the onset of global left ventricular (LV) dysfunction. Asymptomatic: patients with chronic MR and normal left ventricular EF by echocardiography (n=14) underwent cardiac MRI with tissue tagging. The point-specific comparison (at 15,300 LV grid points) of multiple strain parameters to a 60-patient normal human strain database allowed normalization of patient-specific regional contractile function. Data was color-contour mapped over patient-specific 3D geometry, then further averaged across six LV regions (anterior, anterolateral, posterolateral, posterior, posteroseptal, anteroseptal). Global: LV function by multiparametric strain analysis was normal for all 14 MR patients when compared to normal controls. Despite overall preserved global LV function, the LV septum demonstrated significantly worse normalized contractile function when compared to other regions of the LV ( 0.07 ± 0.42 vs -0.40 ± 0.54, p=0.009 ). Hyper-contractile regions (lateral walls) appeared to compensate (p=0.002) for the reduced septal contractile function thereby masking injury detection by global indices. In asymptomatic MR patients with normal global LV function, contractile injury is heterogeneous, with a consistent distribution pattern identifying the LV septum as being injured earliest with contractile compensation by other regions. Rather than relying upon global LV contractile metrics, which does not detect early onset of injury, asymptomatic chronic MR patients should be followed with surveillance of early injury (or “sentinel”) LV regions (LV septum) with high-resolution metrics of regional contractile function.
Abstract 18459: MicroRNA-712 Induced by Angiotensin II Plays a Key Role in Development of Abdominal Aortic Aneurysm in Mouse
Authors: Chanwoo Kim, Sandeep Kumar, Dong Ju Son, In-Hwan Jang, Hanjoong Jo
Journal: Circulation (2013)

Abdominal aortic aneurysm (AAA) is a complex vascular disease and a major cause of mortality. AAA is characterized by a weakening of the vessel wall, followed by progressive expansion of the diseased aortic segment. Although the molecular mechanisms underlying AAA initiation and development are poorly understood, microRNAs (miRNAs) are thought to play a role in these processes. Here we identify microRNA-712 (miR-712) through a microRNA array study as a novel miRNA upregulated in abdominal aortic endothelium in mice infused with angiotensin II (AngII, 1 ug/kg/min for 12 to 36 hours). Through in silico analysis and using gain-of-function [pre-miR-712] and loss-of-function [locked nucleic acid (LNA)-based anti-miR-712] studies, we determined that miR-712 directly regulates the expression of tissue inhibitor of metalloproteinase 3 (TIMP3). Additionally, we confirmed the target-binding activity of miR-712 on the 3’UTR of TIMP3 by dual-luciferase reporter assay. Furthermore, inhibition of miR-712 decreased matrix metalloproteinase (MMP) activity in an AngII-infused abdominal aorta wall. Finally, we showed that inhibition of AngII-induced miR-712 by subcutaneous injection of anti-miR-712 reduced AAA incidence from 80% (8/10) to 20% (2/10) and maximal aortic diameter from 2.1±0.6mm to 1.2±0.4 mm compared to mismatched control in ApoE -/- mice via MMP-mediated mechanisms. Our findings show that miR-712 regulates MMPs activity through the endogenous regulator TIMP3, which leads us to conclude that AngII-induced miRNAs such as miR-712 play important roles in the pathogenesis of AAA. These results suggest that manipulation of miR-712, and its target gene TIMP3 may hold promise as a therapeutic strategy to prevent the development of AAA.
Abstract 18482: Structure Based Prediction of Stability and Affinity Changes in Human NKX2.5 HD Mutants
Authors: Lagnajeet Pradhan, Hideko Kasahara, Hyun Joo Nam
Journal: Circulation (2013)

Background: Cardiac transcription factor, NKX2.5, binds to the target DNA through its homeodomain (HD). To date, nearly 40 mutations in NKX2.5 have been found related to familial congenital heart disease. Homeodomain missense mutations have a high disease penetrance, with pleiotropic cardiac defects compared to missense mutations outside the homeodomain. In in vitro studies, the best correlation with clinical phenotypes and homeodomain mutation resulted from the markedly reduced DNA binding. We recently determined crystal structure of NKX2.5 HD bound to its natural DNA target. Using the structure, we sought to study whether DNA binding and folding energy changes in mutant proteins can be predicted through computational approaches. Methods and results: We used structure based energy prediction to calculate the binding energy and the stability of NKX2.5 mutant proteins. NKX2.5 HD from the high resolution crystal structure (PDB ID: 3RKQ ) was mutated to reflect the 14 genetic and 4 somatic point mutations identified in patients with cardiac anomalies. The HD-DNA models were energy minimized using the program Interface Model. This program utilizes a conservative approach by keeping the backbone structure of the protein and DNA intact while operating only on the sidechain rotamers to achieve the lowest energy state using monte-carlo simulation. Intra-protein and protein-DNA interaction energies of mutant models were calculated and the relative ΔG from the wild type was tabulated. Compared to the wild-type, all the genetic mutants showed reduced DNA binding while the somatic mutations show increased protein stability and DNA binding. The prediction is in good agreement with reported biochemical studies. Conclusion: The high resolution structure enables prediction of energy changes in NKX2.5 pathological mutants compared to wild type. The results well correlate with previously reported experimental data.
Abstract 18267: The Economic Impact of Healthcare Associated Infections in Cardiac Surgery
Authors: Giampaolo Greco, Wei Shi, Robert Michler, Eugene Blackstone, Irving L Kron, Ellen Moquete, Joseph Y Woo, Alan J Moskowitz, Vinod Thourani, A. Marc Gillinov, Annetine C Gelijns, Michael Argenziano, John H Alexander, Louis P Perrault, Albert Lee, Sandra G Burks, Patrick T O’Gara, Emilia Bagiella, Samuel F Hohmann, Timothy J Gardner
Journal: Circulation (2013)

Background: Healthcare-associated infections (HAIs) are the most common non-cardiac complication after cardiac surgery, and are associated with increased morbidity, mortality and resource use. Despite being the focus of quality improvement efforts, there is little information about their economic impact. This prospective cohort study examines the incremental costs associated with HAIs within 65 days of cardiac surgery. Methods: Clinical data on major and minor infections (CDC/NHSN definitions) from 9 academic centers were merged with related financial data routinely collected by the University Health Consortium. Incremental length of stay (LOS) and cost attributable to HAIs were estimated using generalized linear models, adjusting for patient demographics, clinical history, baseline labs and surgery type. Results: The most common procedures in 4313 cardiac surgery patients were isolated valve (31%), isolated CABG (29%), and CABG/valve (12%), with a mean age 64±13 years. During the index hospitalization, 3% of patients experienced major infections, including pneumonia, sepsis, C. Difficile and surgical site infections. The most common minor infection was UTI, which occurred in 2% of patients. The adjusted average incremental cost due to major infection was nearly $50,000 (table), with the additional ICU stay increasing the index hospitalization cost by $1094/day during the first 2 weeks after surgery. Patients with major index HAIs were nearly twice as likely to be readmitted as those without. Overall, there were 855 readmissions; 19 % due to HAIs, costing on average nearly twice as much as non-HAI related readmissions. Conclusions: In an era that emphasizes early discharge and the need to avert preventable readmissions, this study shows that both are heavily influenced by infection rates and that the costs of HAIs in cardiac surgery are substantial. These data provide critical insights about the potential economic impact of infection prevention programs.
Abstract 18538: Subclinical Left Ventricular Dysfunction, Adverse Myocardial and Aortic Remodeling in Patients With Tetralogy of Fallot Late After Surgical Repair
Authors: Carsten Rickers, Ana Andrade, Michael Jerosch-Herold, Inga Voges, Minh H Pham, Ravi Shah, Christopher Hart, Philip Wegner, Dominik Gabbert, Hans Heiner Kramer
Journal: Circulation (2013)

Introduction: In patients after repair of tetralogy of Fallot (ToF) there is increasing evidence that left ventricular dysfunction and dilation may be present even in younger patients, which could potentially accelerate the occurrence of left heart failure. We examined by cardiac magnetic resonance (CMR) imaging if impaired LV function, diffuse myocardial fibrosis, and increased aortic stiffness is prevalent in asymptomatic ToF. Methods: CMR at 3T was performed in 109 asymptomatic ToF patients (age, 19.3±12.8 years) after surgical correction (16.6±10.0 years post operation) and 64 age-matched controls. Parameters of aortic distensibility (at 4 different aortic locations) and ventricular volumes were obtained from cine CMR. In a subset (n=50), myocardial extracellular volume fraction (ECV) was calculated from pre- and post-gadolinium contrast T1 measurements of blood and myocardium accounting for hematocrit. Results: Compared to control subjects, ToF patients had increased indexed LV endsystolic volumes resulting in a lower ejection fraction (LVEF; 50.7 ± 8.8 versus 59.0 ± 5.4; p&lt;0.01). The RV enddiastolic and endsystolic volumes were also increased (p&lt;0.01). Patients with TOF had a higher LV mass-to-volume ratio and increased aortic distensibility, reflecting alterations in ventricular-vascular coupling. Left atrial passive and total ejection fraction were decreased, and were associated with age (p&lt;0.01) suggesting early onset of diastolic dysfunction. ECV was elevated in patients with ToF (0.32 ± 0.05 versus 0.26 ± 0.01 in controls (p&lt;0.01), more so in females (p&lt;0.05), and was inversely associated with indexed LV mass (p&lt;0.05). Conclusion: Asymptomatic repaired ToF patients have subclinical alterations in LV geometry, function, aortic distensibility, and tissue architecture (by ECV). These findings indicate an early adverse cardiovascular phenotype that may reinforce a long-term risk burden of incipient LV failure in addition to effects on the RV.