tbuckley/cabot-search huggingface dataset:
Abstract 19680: Fatalism does not Decrease Effectiveness of interventions to Improve Cardiovasuar Health
Authors: Terry A Lennie, Susan K Frazier, Martha Biddle, M J Novak, Baretta Casey, Gia Mudd, Debra K Moser
Journal: Circulation (2012)

Background: There is a long standing belief that lifestyle interventions to decrease cardiovascular disease (CVD) risk are less effective in individuals who have a fatalistic (preordained) view of health. Rural Appalachian Kentucky is a region perceived to have a culture that includes fatalistic views toward health, which may make lifestyle interventions less effective. One of the most challenging lifestyle modifications is change in diet. Objective: To compare responses of adults with high vs. low levels of fatalism to a life-style intervention to decrease modifiable CVD risk factors including diet. Methods: A total of 280 adults with at least one CVD risk factor participated in a 6-month individualized education and goal setting intervention to promote heart healthy lifestyles. As part of the assessment, participants completed food frequency questionnaires (FFQ) at baseline and post-intervention. Fatalism was measured by the Fatalism Scale. Median split of Fatalism Scale scores was used to divide the sample into 2 groups: higher vs. low levels of fatalism. Repeated measures analysis of variance was used to compare post intervention intake of total fat, saturated fat, calories, total sugar, added sugar, number of daily fruit, vegetable, sweets, and fried food servings between groups. Results: There was a significant decrease post-intervention in total fat, saturated fat, calories, added sugar, and number of sweets and fried foods consumed; while the number of fruit servings consumed daily increased. There were no significant differences post-intervention in nutrient intake between adults with lower vs. higher levels of fatalism; both groups made similar modifications in eating habits. Conclusion: Adults with high levels of fatalism are willing to make appropriate lifestyle changes to decrease their CVD risk. These results provide evidence to dispel the myth that people living in this region are resistant to changes that will improve their health.
Abstract 18025: Cryomaze for Sole-Therapy Atrial Fibrillation
Authors: Ghulam Murtaza, Moritz Wyler von Ballmoos, Saqib Masroor
Journal: Circulation (2011)

Objectives: Surgical AF treatment program was started at our institution in August 2008. We report our initial results using minithoracotomy approach for endocardial cryomaze. Methods: All 30 patients undergoing Cryomaze between 8/08 and 12/10 are included. 1 patient underwent MVR while two others needed sternotomy for incidental aortic aneurysm and coronary artery disease diagnosed during preoperative workup. Surgical technique consisted of femoral cannulation for cardiopulmonary bypass and right mini-thoracotomy with video-assistance. Aortic root vent used in all cases and Chitwood clamp was used in arrested heart cases. On the left side, all pulmonary veins were isolated as an island and another line was made to the mitral annulus (LA isthmus line). On the right side, SVC was connected to IVC and this line was connected to tricuspid annulus (RA isthumus line). Left atrial appendage was oversewn in two layers, except during sternotomy, where it was stapled off with endo-GIA stapler. Beta blockers were used as tolerated and amiodarone was only used if patient developed AF. Postprocedure follow-up included spot EKG at 1, 3, 6 and 12 months and yearly thereafter. Symptomatic patients underwent three week continuous rhythm monitoring. Results: Outcomes are given in table below. 4(13%) patients required permanent pacemakers. There were 6 (20%) complications including catheter ablation for atrial tachycardia, pericardial effusion (no intervention needed), subcutaneous emphysema, lung hernia, femoral lymph leak and reopening of one LAA. There were no mortalities or strokes. Conclusions: Minimally invasive Cryomaze has acceptable morbidity and excellent short-term results in treating AF. Freedom from AF in this series was not influenced by left atrial vs biatrial ablation, beating heart vs arrested heart ablation, primary vs prior failed catheter ablation, or Paroxysmal vs Persistent AF.
Abstract 9264: Predicting Acute Coronary Heart Disease Events in Women
Authors: Jean C McSweeney, Mario Cleves, Ellen Fischer, Jeanne Wei, Debra Moser
Journal: Circulation (2011)

Background: Coronary heart disease (CHD) is treatable if detected early yet few instruments measure women's prodromal symptoms (PS) of CHD. The McSweeney Acute and Prodromal Myocardial Infarction Symptom Survey (MAPMISS) identifies women's PS but prospective cohort data regarding the MAPMISS' predictability is limited. Purpose: To conduct a longitudinal observational cohort study designed to assess the ability of the MAPMISS' PS score to predict CHD events requiring clinical intervention in women, and to identify the most predictive components of the MAPMISS' PS score. Methods: Women referred for initial cardiac evaluation to clinics in Arkansas and Kentucky were eligible to participate; those with previous cardiac events and cognitive impairment were excluded. A total of 1114 women participated. The MAPMISS questionnaire was administered at time of enrollment and subsequently every 3 months for two years. The MAPMISS contains 33 PS. Each PS is weighted by its reported severity (0-3, 3=most severe) and frequency (less than monthly to daily, 0.125-7, 7=daily), and summed across symptoms (range 0-693). Cox proportional-hazards models adjusted by age and race were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (CI) for CHD events. Prodromal symptoms were entered in the Cox model as time dependent covariates. Results: Of the 1114 women, 1097 (98.5%) completed the study. Of these, 77 (7%) reported having an adverse cardiac event during the two-year follow-up. The total PS score was a significant predictor of adverse cardiac events (p&lt;0.001). Back pain, between/under shoulder blades, was the strongest predictor of adverse cardiac events (HR=3.17, 95%CI = 1.28- 7.85), followed by change in thinking or remembering (HR=2.90, 95%CI = 1.20- 7.04), and non-specific, generalized chest pain (HR=2.97, 95%CI = 1.04- 8.50). Women reporting one or more of these three symptoms were over 5 times as likely to have an adverse cardiac event as women with none of these symptoms (HR=5.25, 95%CI = 2.37- 11.64). Conclusion: The total PS score from the MAPMISS could be useful in screening women at risk of an adverse cardiac event.
Abstract 18299: Prevalence of and Correlates with QRS Prolongation in Heart Failure with Preserved Ejection Fraction: Data from the KaRen Study
Authors: Lars H Lund, Erwan Donal, Emmanuel Oger, Camilla Hage, Hans Persson, Moa Simonsson, Ida Haugen-Löfman, Jean-Claude Daubert, Cecilia Linde
Journal: Circulation (2012)

Background: QRS ≥ 120 ms is present in 1/3 of patients with heart failure with reduced ejection fraction, favorably treated with cardiac resynchronization therapy. In heart failure with preserved ejection fraction (HFPEF), the prevalence of and correlates with QRS prolongation are largely unknown. Methods: KaRen is a multicenter prospective registry of HFPEF (ClinicalTrials.gov NCT00774709 ). Inclusion criteria are Framingham symptoms and signs of heart failure together with NT-proBNP &gt;300 ng/L and LVEF ≥45%. In patients with sinus rhythm and with atrial fibrillation / flutter (AF), the prevalence of and association between QRS prolongation and clinical characteristics was assessed with uni- and multivariable linear regression, with 10 clinical variables, ejection fraction, and EKG parameters (10 in sinus rhythm; 6 in AF), using backward step-wise selection based on p &lt; 0.10. Results: We studied 382 patients, mean (SD) age 77 (9) years, 56% women. QRS &lt; 120 ms, 120-149 ms, ≥ 150 ms, LBBB, and ventricular-paced EKG was present in 78, 11, 3, 3 and 8% respectively. One-hundred twenty-six patients (35%) had AF. AF was not associated with QRS width. The table lists variables independently associated with QRS in ms, their baseline values and Beta coefficients, separately among patients in sinus rhythm and AF, excluding ventricular-paced patients. Conclusions: In HFPEF, QRS prolongation and LBBB are less common than in reduced ejection fraction. QRS prolongation is associated with other EKG pathology and with B-blocker use. The rarely measured parameter “P-wave duration” may reflect the same underlying global conduction delay as QRS duration.
Abstract 18372: Clinical Threshold of Adenovirus Genome Load in Myocardial Tissues of Patients with Myocarditis and Dilated Cardiomyopathy
Authors: Mirnalini Sharma, Baijayantimala Mishra, Vandana Kumari, Uma N Saikia, Ajay Bahl, Radha K Ratho, Kewal K Talwar
Journal: Circulation (2011)

Background: Viral myocarditis is rarely recognized hence it is one of the most challenging diagnosis in cardiology. It leads to chronic dilated cardiomyopathy (DCM) and heart failure. Adenovirus is one of the most common cardiotropic viruses that cause viral myocarditis. However, the knowledge on AdV load in adenovirus associated myocarditis or DCM is unknown so far. Aim: To gain insight into the pathogenesis of AdV associated myocarditis, present study was aimed to determine AdV load in myocardial autopsy tissue of patients with myocarditis or DCM. Methods and Results: AdV load was determined using Taqman Real Time PCR in myocardial autopsy tissues obtained from 24 (11 male and 13 female) patients with histologically proven myocarditis or DCM whereas 12 noninflamed normal hearts obtained from autopsies served as controls. The AdV associated myocarditis was characterized by high mean viral load of 2034 genome equivalents (ge) per microgram of isolated nucleic acids in DCM patients with myocarditis as compared to viral load of 362 genome equivalents (ge) per microgram in normal hearts (p&lt;0.005). Thus, from this data possibly AdV loads of more than 450 ge per microgram in myocardial autopsy are clinically relevant threshold for the maintenance of myocardial inflammation. Conclusion: The present study could derive the significant level of adenovirus load of 450 ge per microgram in myocardial tissues to be associated with adenovirus myocarditis and DCM. The knowledge on the clinical threshold of adenovirus load would help in diagnosing the clinically suspected viral myocarditis or DCM cases as well as would help in establishing an antiviral strategy to treat these patients.
Abstract 18569: Impact of ER-Stress Affecting Variant of XBP-1 Gene on Lipids, Diabetes, Chronic Kidney Disease, and Coronary Artery Disease
Authors: Atsushi Nohara, Tohru Noguchi, Takeshi Inoue, Mika Mori, Chiaki Nakanishi, Masa-aki Kawashiri, Kunimasa Yagi, Akihiro Inazu, Junji Kobayashi, Masakazu Yamagishi, Hiroshi Mabuchi
Journal: Circulation (2012)

Objective: ER function is fundamentally important in all cell types, and the key transcription factor X-box binding protein 1 (XBP-1) regulates many genes of ER-stress and also hepatic lipogenesis. A functional polymorphism (-116G&gt;C) in the promoter region of XBP1 has been identified, and -116C allele was associated with higher ER-stress in vitro . CC homozygotes are quite common in Japanese (41%) compared with European (7% in NCBI database). Even though higher ER-stress would be associated with coronary risk factors, few data exist regarding clinical importance of this polymorphism as a cardiovascular risk factor. Methods: A total of 272 patients (137 males, mean age of 57 ± 14) suspected coronary artery disease were enrolled. Genotypes were determined by PCR-RFLP, and lipid profiles with ultracentrifugation, 75gOGTT, post-heparin lipoprotein lipase activities (PHLA), and eGFR were analyzed. Coronary stenosis index (CSI) was estimated with angiography in 125 patients (69 males, mean age of 63 ± 11, Diabetes 45%). Results: No difference was observed in age and sex with genotypes. CC homozygotes showed higher BMI (CC vs. GC+GG = 24.8 ± 3.3 vs. 23.4 ± 3.2, p &lt;0.05). CC homozygotes showed higher apoB/LDL-C ratio (0.94 ± 0.1 vs. 0.87 ± 0.1, p &lt;0.05), and higher LDL-TG (46 ± 94 vs. 28 ± 21, p &lt;0.05) suggesting presence of small dense-LDL. CC homozygotes showed higher hepatic transaminases, suggesting hepatic inflammation such as NAFLD. Hypertension was more frequent in CC homozygotes (79 vs. 54%, P&lt;0.05). Also C carriers showed lower eGFR (CC+GC vs. GG = 77.3±21 vs. 83.0±24, p &lt;0.05). Unexpectedly, CC homozygotes showed higher HOMA-beta (141 ± 178 vs. 91 ± 56, p &lt;0.05), and lower HbA1c (5.9 ± 1.0 vs. 6.3 ± 1.3 %, p &lt;0.05). In coronary angiography, CC homozygotes showed higher CSI in non-diabetes group (21 ± 9 vs. 11 ± 11, p &lt;0.005), but not significant in diabetes group. Conclusion: Functional XBP1 variant showed significant impacts on advanced coronary artery disease with deteriorating lipid profile, hypertension, and chronic kidney disease.
Abstract 18366: Cutoff of 1.0 cm <sup>2</sup> For Severe Aortic Stenosis? A Case for Redefining this Cutoff Based on Eccentricity of LVOT Geometry
Authors: Praveen Mehrotra, Gary Mak, Katrijn Jansen, Xin Zeng, Aidan Flynn, Jon Passeri, Judy Hung
Journal: Circulation (2011)

Background: Current guidelines define severe aortic stenosis (AS) as aortic valve area (AVA) of &lt;1.0 cm 2 . This cutoff is based on the assumption of a circular left ventricular outflow tract (LVOT) cross sectional area (CSA) for the continuity equation (CE). However, patients with AS have chronic pressure load and may have remodeling of the LVOT geometry from circular to elliptical. An elliptical LVOT with a smaller dimension in the anterior-posterior plane would result in a lower calculated AVA. Many patients have discrepant indices of severe AS where AVA by CE is severe (&lt;1.0 cm 2 ) yet peak velocity (V2) and mean gradient (MG) are in the moderate or mild range. We hypothesized that discordance of AS severity by AVA versus V2 or MG may be due to inaccurate circular LVOT CSA assumption in patients with AS where chronic pressure load results in an elliptical LVOT geometry. Methods: We assessed LVOT geometry by direct planimetry using 3D transesophageal echo (TEE) and calculated an eccentricity index (ratio of two orthogonal linear measurements and also ratio of CSA direct planimetry/CSA by circular LVOT assumption) in 54 patients with severe AS undergoing TTE and TEE within one month of each other. We compared AVA by elliptical LVOT (AVA LVOT ) to conventional circular LVOT CE. We then applied a correction factor for AVA underestimation based on the measured LVOT eccentricity index in a separate cohort of 49 patients with discrepant AS indices (AVA &lt;1.0 cm 2 but MG &lt;30 mmHg). Results: LVOT shape was elliptical in 53 of 54 (98%) patients with a mean eccentricity index of 0.88 ± 0.06 by 3D TEE. The mean LVOT CSA assuming circular geometry underestimated the true CSA determined by direct planimetry by approximately 14% (3.25 vs. 3.71 cm 2 , p&lt;0.001). AVA LVOT was higher than AVA by conventional CE (0.71 vs. 0.61 cm 2 , p=0.003). After multiplying the LVOT CSA by correction factor of 1.14 (to account for 14% underestimation of LVOT area) in 49 patients with discrepant severe AS (mean AVA, V2 and MG of 0.88 cm 2 , 3.2 m/s and 23 mmHg, respectively), the mean AVA increased to 1.0 cm 2 . Conclusions: The LVOT geometry in patients with AS is predominantly elliptical with an eccentricity index of 0.88. The cutoff for severe AS valve area by conventional CE should be 0.8 cm 2 to adjust for elliptical LVOT geometry.
Abstract 18310: Angiotensin Converting Enzyme Gene Polymorphism is Associated with Reverse Remodeling of Left Atrium after Catheter Ablation of Atrial Fibrillation
Authors: Jaemin Shim, Hee-Sun Mun, Jin Wi, Jae Hyung Park, Jae Sun Uhm, Jong Youn Kim, Boyoung Joung, Moon-Hyoung Lee, Hui-Nam Pak
Journal: Circulation (2012)

Background: Although it has been known that radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) induces reverse remodeling of left atrium (LA) and improves left ventricular (LV) function, its mechanism has not been evaluated yet. We hypothesized that genetic polymorphisms in angiotensin converting enzyme (ACE) or angiotensin II type 1 receptor (AT1R) genes may contribute to the changes after RFCA. Methods: We included 263 patients with AF (male 78%, 56±11 years old, paroxysmal AF 70%) who underwent RFCA of AF, and compared pre-procedural and post-RFCA 1-year follow-up echocardiography. LA reverse remodeling was defined as decreased LA size at 1-year after RFCA. Potential 4 ACE (rs4341, rs4362, rs4309, rs4291) and 3 AT1R (rs2675511, rs422858 , and rs5182) related single nucleotide polymorphisms (SNPs) were genotyped and compared with phenotypes of AF patients. Results: Mean LA size decreased (41.4±6.1 vs. 38.5±5.8 mm, p&lt;0.001) at 1-year after RFCA and the reduced LA size after RFCA was observed in 72.2% of patients (n=190). The patients with reverse remodeling were more likely to have larger preprocedural LA size (42.6 ± 5.9 vs. 38.4 ± 5.3 mm, p&lt;0.001) than those without it. Mean LV ejection fraction (LVEF, 63.3±7.8 vs. 65.2±7.5%, p&lt;0.001) increased at 1-year and E/E’ decreased (18.7±4.0 vs. 14.6±3.3 mm, p&lt;0.001) in patients with baseline LV diastolic dysfunction (E/E’≥15). Among the 7 SNPs, ACE gene, rs4309 and rs4291 variants, were significantly associated with reverse remodeling of LA (CC vs. CT+TT; OR 0.407; 95% CI 0.189-0.879, TT vs. AT+AA; OR 0.307; 95% CI 0.114-0.827, respectively). A multiple logistic regression analysis showed that the rs4309 variant (OR 0.400; 95% CI 0.179-0.896) and preprocedural LA size (OR 1.147; 95% CI 1.083-1.215) were independent predictors of the reverse remodeling of LA. Conclusions: Reduction of AF burden by catheter ablation induces reverse remodeling of LA and improves LV systolic and diastolic function, especially in patients with baseline LV diastolic dysfunction. Several ACE polymorphisms were associated with such reverse remodeling of LA in patients with AF.
Abstract 19761: P27 Inhibits IkBa-Degradation, Attenuates Inflammation, Improves Cardiac Function and Increases Survival Following LPS
Authors: Filip Konecny, Jian Zou, Charlene Antony, Mansoor Husain, Rudiger von Harsdorf
Journal: Circulation (2012)

Background : A previous cardiac protein interaction screen suggested that cell cycle inhibitor p27 interacts with IKKα, a kinase that regulates phosphorylation-dependent degradation of IκBα, the inhibitor of NF-κB. Bacterial toxin LPS promotes NF-κB-induced myocarditis. Here we test if p27 can interfere with LPS-induced cardiac dysfunction in vivo . Methods : At 1 and 6 h post-LPS (30 mg/kg i.p.), an HA-tagged TAT-conjugated p27 fusion protein (TAT.p27), a TAT.lacZ control or an equal volume of saline was delivered (20 mg/kg i.p.) to 8-wk old C57BL6 mice. This dose of TAT.p27 was shown capable of entering the heart and increasing total cardiac p27 levels as determined by immunofluorescence for HA-tag and Western blot (WB) for p27. Cardiac structure and function were assessed by 2D-echo and pressure-volume catheters. WBs of heart homogenates for cleaved caspase-3 and Bcl-2, as well as IκBα, were used to assess apoptosis and IκBα turnover. Expression of inflammatory cytokines IL-1β and IL-6 was measured by RT-PCR. Survival was analyzed by Kaplan-Meier plots. Results : Delivery of TAT.p27 at 1 h post-LPS preserved myocardial levels of IκBα at 1.5, 2 and 4 h post-LPS. Co-immunoprecipitation experiments in intact heart showed an interaction between p27 and IκBα. Delivery of TAT.p27 at 6 h post-LPS resulted in improvements vs. saline and TAT.lacZ controls in fractional shortening (%: 38.2±1.2 vs. 29.1±1.5, P&lt;0.01; vs. 27.3±1.8, P&lt;0.001), cardiac output (µl/min: 17332±4619 vs. 12279± 5304, p&lt;0.05; vs. 12959±3221; p&lt;0.01), stroke volume (µl: 28±7 vs. 21±8, p&lt;0.01; vs. 20±5 µl, p&lt;0.05) and stroke work (mJ: 2121±909 vs. 1472±721, p&lt;0.05; vs. 1366±522, p&lt;0.05). For each above result, N≥13 per group. Apoptosis was significantly decreased in TAT.p27-treated mice subjected to LPS, as were mRNA levels of IL-1β and IL-6 as compared to controls. Importantly, these improvements were associated with better survival in TAT.p27-treated mice vs . saline- and TAT.lacZ-treated controls. Conclusion : These data suggest that the p27-IκBα and or IKKα interactions, possibly by preserving cardiac IκBα levels and preventing NFκB activation post-LPS, attenuate inflammation, limit cardiomyocyte apoptosis, and improve survival in a model of endotoxin-induced cardiac dysfunction.
Nivolumab for mismatch-repair-deficient or hypermutated gynecologic cancers: a phase 2 trial with biomarker analyses
Authors: Claire F. Friedman, Beryl L. Manning-Geist, Qin Zhou, Tara Soumerai, Aliya Holland, Arnaud Da Cruz Paula, Hunter Green, Melih Arda Ozsoy, Alexia Iasonos, Travis Hollmann, Mario M. Leitao, Jennifer J. Mueller, Vicky Makker, William P. Tew, Roisin E. O’Cearbhaill, Ying L. Liu, Maria M. Rubinstein, Tiffany Troso-Sandoval, Stuart M. Lichtman, Alison Schram, Chrisann Kyi, Rachel N. Grisham, Pamela Causa Andrieu, E. John Wherry, Carol Aghajanian, Britta Weigelt, Martee L. Hensley, Dmitriy Zamarin
Journal: Nature Medicine (2024)

Programmed death-1 (PD-1) inhibitors are approved for therapy of gynecologic cancers with DNA mismatch repair deficiency (dMMR), although predictors of response remain elusive. We conducted a single-arm phase 2 study of nivolumab in 35 patients with dMMR uterine or ovarian cancers. Co-primary endpoints included objective response rate (ORR) and progression-free survival at 24 weeks (PFS24). Secondary endpoints included overall survival (OS), disease control rate (DCR), duration of response (DOR) and safety. Exploratory endpoints included biomarkers and molecular correlates of response. The ORR was 58.8% (97.5% confidence interval (CI): 40.7-100%), and the PFS24 rate was 64.7% (97.5% one-sided CI: 46.5-100%), meeting the pre-specified endpoints. The DCR was 73.5% (95% CI: 55.6-87.1%). At the median follow-up of 42.1 months (range, 8.9-59.8 months), median OS was not reached. One-year OS rate was 79% (95% CI: 60.9-89.4%). Thirty-two patients (91%) had a treatment-related adverse event (TRAE), including arthralgia (n = 10, 29%), fatigue (n = 10, 29%), pain (n = 10, 29%) and pruritis (n = 10, 29%); most were grade 1 or grade 2. Ten patients (29%) reported a grade 3 or grade 4 TRAE; no grade 5 events occurred. Exploratory analyses show that the presence of dysfunctional (CD8