tbuckley/cabot-search huggingface dataset:
Abstract 16635: Cost Effectiveness Analysis of the Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction REVIVED Trial Data
Authors: Carlos Chivardi, Mark Sculpher, Matthew Dodd, Holly Morgan, Matthew J Ryan, Richard Evans, C Aldo Rinaldi, Peter O'Kane, Tim Clayton, Mark Petrie, Divaka Perera, Pedro Saramago
Journal: Circulation (2023)

Introduction. Evidence on survival benefits of percutaneous coronary intervention (PCI) in patients with severe ischemic left ventricular systolic dysfunction (ILVD) is scant. The REVIVED trial showed that, compared to optimal medical therapy (OMT), revascularisation by PCI did not reduce the incidence of death from any cause or heart failure hospitalization (HF); it also failed to provide sustained improvements in health-related quality of life. REVIVED data are used to evaluate the economic consequences and health outcomes of PCI+OMT and OMT alone in HF patients in the UK. Methods. 700 patients with ILVD were randomised to either PCI+OMT or OMT. Healthcare resource use and patient-reported health outcomes data EuroQol on each patient were collected at baseline and over a period of 8 years post randomisation (median follow up of 3.5 years). Health resources were costed using publicly available national unit costs from the perspective of the UK health system. Within trial mean total costs and quality adjusted life years (QALYs) were estimated and incremental cost effectiveness was evaluated. Regression analysis on total costs and total QALYs was used to adjust for clinically relevant baseline covariables. Probabilistic sensitivity analysis was used to reflect parameter uncertainty. Results. Statistical modelling identified gender, BMI, hypertension, diabetes, NYHA grade and previous hospitalisation as the most relevant baseline predictors of costs and benefits. Over the 8 years of fu, patients undergoing PCI yielded, on average, similar health benefits (4.13 QALYs IC [4.10 - 4.16]) at higher costs (£14,674 IC[£14,334 - £15,014]), compared to OMT (4.16 QALYs [4.13 - 4.19]; £5154 IC [£5,034 - £5,273]). Conclusion. We found no difference in total QALYs between arms and PCI+OMT was not cost-effective compared to OMT, given its additional costs. Therefore, a strategy of routine PCI to treat ILVSD does not appear to be a justifiable use of healthcare resources.
Abstract 12832: Risk of Extreme Wet Climate Conditions and Racial/Ethnic-Specific Cardiovascular Mortality in Southwest United States
Authors: Haris Majeed, Hamnah Majeed, Steve Singh, John Coles
Journal: Circulation (2023)

Introduction: Coastal regions are highly vulnerable to extreme climate conditions, which are known to have effects on adult cardiovascular disease mortality (CVDM). Racial/ethnic (R/E) minority populations (ie Non-Hispanic (NH) Black) are known to have a greater incidence of CVDM compared to their NH White counterparts. Consequently, there is a need to document associations between climate extremes and R/E-specific CVDM. Hypothesis: Extreme wet conditions associated with CVDM should vary by R/E, where strongest increased risk is expected for minority populations. Methods: Population-based study using sex, age (45-84 years), and R/E-specific (NH White, Black, Asian, &amp; Hispanic/Latino) CVD deaths [ICD-10 (I00-99)] from CDC for Southwest US (California, Arizona, New Mexico) from Jan 1999 to Dec 2020. Climate exposure categories (mild, moderate, extreme dry/wet) were based on Palmer Drought Severity Index (PDSI), which integrates temperature and precipitation. With population estimates, CVDM rates were associated with PSDI categories using negative binomial regression upon adjusting for diabetes, smoking prevalence, sex, trend, month, state, unemployment rate, and air pollution (PM 2.5 ). Results: From 1999-2020, 1,307,418 (67.6% NH White, 16.1% Hispanic, 7.4% NH Asian, 8.9% NH Black) CVD deaths were recorded. CVDM was associated with a significant increased risk during extreme wet events (compared to extreme drought) only among NH Asian (adjusted rate ratio [RR] 1.08; 95% CI 1.06-1.09) and NH White (RR 1.02; 95% CI 1.01-1.025) in Southwest US (Figure). Insignificant interactions were observed between extreme wet and PM2.5 on CVDM by R/E. Conclusions: Extreme wet climate conditions were associated with an increased risk of CVDM among NH Asian and White adults. Both climate extreme events and R/E should be considered as predisposing risk factors for CVDM. Further studies are needed to assess such CVDM risk factors for other susceptible areas in the US.
Abstract 15314: Rhythm Outcome of Persistent Atrial Fibrillation Ablation Depending on the Timing of the First Electrocardiographic Documentation
Authors: Hongju Kim, Kipoong Kim, Daehoon Kim, Sung Hwa Choi, Moon-Hyun Kim, Je W Park, Hee Tae Yu, Jae-Sun Uhm, BOYOUNG JOUNG, Moon Hyoung LEE, Hui-Nam Pak
Journal: Circulation (2023)

Introduction: Recently, delaying atrial fibrillation (AF) catheter ablation (AFCA) by 12 months for antiarrhythmic drug (AAD) management didn't result in reduced ablation efficacy. In this study, we explored AFCA rhythm outcomes based on the diagnosis-to-ablation time (DAT) in AAD-resistant persistent AF (PeAF). Methods: We included 1,038 AAD-resistant PeAF patients with clear DAT (male 79.8%, 61.0 [54.0-68.0]) who underwent AFCA followed by guidelines-based regular rhythm follow-up. Before AFCA, all patients underwent optimal medial therapy (AAD) with or without cardioversion. Patients on AADs, who experienced paroxysmal type recurrence, were classified as AAD-partial-responders, while those maintaining PeAF were categorized as AAD-non-responders. We determined the DAT cut-off for rhythm outcome using a maximum likelihood approach in a Cox regression model. Results: AAD-partial-responders showed higher body mass index (p=0.007), larger left atrial diameter (p&lt;0.001), lower eGFR (p=0.039). AAD non-responder showed higher recurrence after AFCA (Log-rank p&lt;0.001; aHR 1.75, 95% CI 1.33-2.30, p&lt;0.001). The maximum likelihood estimation from Cox analysis showed bimodal peaks at 22 and 40 months. In contrast, DAT 12 months didn't show discrimination power for post-AFCA recurrence (Log-rank p=0.290, HR1.13[0.91-1.41], p=0.281), while DAT&gt;22 months (Log-rank p=0.001, HR1.34[1.09-1.64], p=0.005) and DAT&gt;40 months (Log-rank p=0.001, HR1.34[1.09-1.64], p=0.006) significantly indicated poor rhythm outcome. DAT&gt;22 months among AAD-partial-responders (Log-rank p=0.012, HR 1.96 [1.16-3.31], p=0.012) and DAT&gt;40 months among AAD-non-responders (Log-rank p=0.009, HR 1.28 [1.02-1.60], p=0.031) were a poor prognostic factor for rhythm control after AFCA. Conclusions: DAT and AAD responsiveness affected the rhythm outcome of AFCA. Delaying AFCA over 22 months of DAT is not desirable in PeAF patients even under optimal medical therapy with AADs.
Abstract 13767: Cardiac Reprogramming Reduces Fibrosis and Improves Diastolic Dysfunction in Heart Failure With Preserved Ejection Fraction
Authors: Yu Yamada, Taketaro Sadahiro, Koji Nakano, Seiichiro Honda, Yuto Abe, Ryo Fujita, Masaki Ieda
Journal: Circulation (2023)

Introduction: Heart failure with preserved ejection fraction (HFpEF) is a disease associated with high morbidity and mortality. Cardiac fibroblasts (CFs) contribute to HFpEF pathogenesis through interstitial/perivascular fibrosis and diastolic dysfunction; however, little is known regarding the mechanisms of the fibrosis, and therapies targeting it are lacking. Cardiac reprogramming is a promising approach for myocardial infarction by overexpressing Mef2c/Gata4/Tbx5/Hand2 (MGTH) in CFs, however, it remains undetermined whether cardiac reprogramming is effective in HFpEF. Aims: This study aims to determine the effectiveness of cardiac reprogramming in HFpEF. Methods: We generated a novel Tcf21iCre/Tomato/MGTH2A transgenic mouse system, where cardiac reprogramming can be induced in a druggable manner with lineage tracing. We first tested whether this system could improve the HFpEF mouse model. To determine the efficacy of cardiac reprogramming and the mechanisms of cardiac fibrosis in HFpEF, we performed multi-omics, including single cell RNA-sequencing (scRNA-seq), spatial transcriptomics, and epigenome analysis. Finally, we generated mouse lines that induce each of the reprogramming factors and investigated whether overexpression of a single factor alone could improve HFpEF, which we also examined in human CF. Results: We found that cardiac reprogramming reduced fibrosis and improved diastolic dysfunction in HFpEF. scRNA-seq and spatial transcriptomics revealed that multiple CF clusters upregulated fibrotic profiles to induce diffuse interstitial fibrosis, whereas the distinct profibrotic CF cluster contributed to perivascular fibrosis, which were reversed with cardiac reprogramming. Mechanistically, cardiac reprogramming changed the epigenetic landscape by recruiting Gata4 to loci. Notably, overexpression of only Gata4 improved HFpEF by reducing fibrosis and suppressed profibrotic signatures in human CFs without generating cardiomyocytes. Conclusions: Cardiac reprogramming may be a promising approach for HFpEF via anti-fibrosis.
Abstract 11840: Outcomes and Disparities of Asian Patients With Severe Chronic Kidney Disease Admitted for Heart Failure
Authors: Samuel Tan, Wenchy Siu, Shasawat Kumar, Paulus Adinugraha
Journal: Circulation (2023)

Introduction: Socioeconomic disparities in cardiovascular and renal disease pose global public health challenges Despite its large population, Asia lacks proportional representation in heart failure (HF) data, limiting our understanding of risk factors and outcomes for Asians with HF and severe CKD. This study aims to explore the sex, racial, and ethnic differences in in-hospital all-cause mortality, baseline risk factors, and in-hospital complications among Asian patients admitted for HF with CKD. Hypothesis: Asian patients with CKD admitted for HF are linked with increased mortality, in-hospital complications, higher costs, and a longer length of stay compared to non-Asian patients. Methods: This retrospective study included patients 18 or older with heart failure and CKD 3-5 on discharge from 2016 to 2019. Multivariate logistic regression calculated the odds ratio (OR) adjusting for Elixhauser co-morbidities, age, and sex. The primary outcome was disparities in racial/ethnic, sex, and age of in-hospital mortality of patients admitted for HF complicated by CKD. Results: This study involved 510,525 patients, revealing Hispanics (OR: 0.791; CI: 07125-0.8747; p&lt;0.001) and African Americans (OR: 0.664; CI: 0.608-0.7258; p&lt;0.001) were associated with significantly lower mortality compared to Asians. Controlling for age and gender, Asians with HF &amp; CKD had significantly higher odds of diabetes, hyperlipidemia, and hypertension compared to non-Asians. Asian males with HF and CKD were associated with significantly higher odds of mortality (OR: 1.072; CI: 1.037-1.109; p&lt;0.001) and cardiovascular co-morbidities including atrial fibrillation, coronary bypass graft, implantable pacemaker, and chronic ischemic heart disease compared to non-Asian males. Asians, compared to non-Asians, were associated with significantly higher odds of acute MI, acute kidney injury, sepsis, and PRBC transfusion when controlling for Elixhauser co-morbidities. Conclusions: This study reveals significant health disparities among Asian patients with HF and CKD. The significant difference in odds of mortality and cardiovascular co-morbidities indicates the need for further research regarding the possible causality of such disparities.
Abstract 16457: Characterization of LTBP2 Mutation in Causing Mitral Valve Prolapse
Authors: Shoshi shpitzen, Haim Rosen, Ayal Ben-Zvi, Karen Meir, Galina Levin, Amichay Gutgold, Shifra Ben-Dor, rebecca haffner, Donna Zwas, David Leibowitz, Robert A Levine, Dan Gilon, Eran Leitersdorf, Idit Tessler, Noga Reshef, Ronen Durst
Journal: Circulation (2023)

Introduction: Mitral Valve Prolapse (MVP) is a cardiac valvular disorder often associated with significant morbidity and mortality with a prevalence of 2.4% in the general population. Familial studies of MVP suggest an autosomal dominant model of inheritance with incomplete penetrance. Hypothesis: The aim of the current study was to identify a genetic etiology for MVP through trait segregation in a progeny with MVP. Methods: We used exome sequencing and segregation analysis to identify mutations linked to MVP in a progeny which includes members. We then generated two strains of mice using Crisper-Cas9 technology, a complete knockout and a knock-in mouse of the top candidate mutation. At 6 months of age echocardiography was done, the mice were sacrificed and the valves were examined pathologically as well as histologically by Movat pentachrome staining. The readers of both the echo and histology were blinded to the genotype. Results: Of 11 genes with rare deleterious mutations only LTBP2 Val1506Met variant (minor allele frequency of 0.0001) segregated with the trait with a LOD score of 1.5[-DR1] . Knockout mice were more likely to demonstrate myxomatous changes by histology (7 of 9 vs 2 of 6 animals, p=0.03) and echocardiography (14 of 22 vs 1 of 8, p=0.01). Knock-in mice demonstrated significantly higher phenotype rate by histology (8 of 8 vs 0 of 7, p&lt;0.0005) and higher nominal phenotype by echo (4 of10 vs 1 of 9, p=0.2). Conclusions: LTBP2 Val1506Met variant segregated with MVP in a large pedigree. Animal models that recapitulate the phenotype suggest that the mutation is indeed pathogenic and leads to myxomatous valvular change.
Abstract 13576: Long-Term Serial Changes in Echocardiographic Parameters in Patients With Heart Failure With Preserved Ejection Fraction After Catheter Ablation for Atrial Fibrillation
Authors: Taiji Okada, Atsushi Kobori, Madoka Sano, Junichi Ooka, Murai Ryousuke, Yasuhiro Sasaki, Toshiaki Toyota, Tomohiko Taniguchi, Kitae Kim, Natsuhiko Ehara, Makoto Kinoshita, Tomoko Tani, Yutaka Furukawa
Journal: Circulation (2023)

Background: Heart failure with preserved ejection fraction (HFpEF) is frequently complicated by atrial fibrillation (AF). Catheter ablation for AF is an effective method for restoring and maintaining sinus rhythm (SR). However, there is limited data on the serial changes in echocardiographic parameters in patients with HFpEF after ablation. Hypothesis: The serial changes in echocardiographic parameters after ablation for AF depend not only on baseline rhythm but also on the presence of HFpEF. Methods: A retrospectively review was conducted on 1109 out of 2123 patients who had serial echocardiographic data available before the ablation procedure and at 1-year, 2-year, and 3-year follow-ups. The changes in echocardiographic parameters were assessed using repeated measures ANOVA with a Greenhouse-Geisser correction and Bonferroni tests in four groups, which were divided according to baseline rhythm and HFpEF. HFpEF was defined as an HFA-PEFF score ≥ 5 or 2-4 and left atrial pressure ≥ 15 mmHg at the time of catheter ablation. Results: The prevalence of HFpEF was 51.9%, and paroxysmal AF was present in 65%. Left atrial volume index (LAVI) was larger at baseline in patients with AF and significant decreased after ablation in all groups. The trend of left atrial emptying fraction (LAEF) increased in patients with baseline AF until 1year later, while in patients with baseline SR and HFpEF, LAEF gradually declined even after catheter ablation. The trend of left ventricular ejection fraction increased in patients with baseline AF. The trend of mean E/E’ mildly increased after ablation in all groups. There were significant differences between HFpEF and non-HFpEF. (Figure) Conclusions: Catheter ablation was associated with changes of LA size, function and left ventricular function. Baseline rhythm and the presence of HFpEF play a complex role in the course of cardiac function after ablation.
Abstract 17689: Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing
Authors: James Malcolmson, Rebecca Hughes, Tim Husselbury, Kamran Khan, Annastazia E Learoyd, Martin Lees, Eleanor Wicks, Jamie Smith, Alexander Simms, James Moon, Luis Lopes, Constantinos O’Mahony, Neha Sekhri, Perry M Elliott, Steffen E Petersen, Mehul B Dhinoja, Saidi A Mohiddin
Journal: Circulation (2023)

Introduction: Patients with refractory symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy (HCM) have extremely limited therapeutic options. Hypothesis: We hypothesized that site-specific-pacing would induce regionalized contractile dyssynchrony to reduce LVMCO gradients and improve symptoms. Methods: Symptomatic-drug-refractory LVMCO patients were recruited for a randomized blinded trial of personalized prescription of pacing (PPoP). Multiple LV and apical RV pacing sites were assessed during invasive hemodynamic study. Patient-specific optimal pacing site and atrioventricular (AV) delays were selected on basis of LVMCO gradient reduction and pacing parameters. Patients were randomized to 6 months active or back-up pacing in cross-over design. Primary outcome examined invasive gradient change with PPoP. Secondary outcomes assessed quality of life and exercise. Results: A total of 17 patients were recruited; 16 met primary endpoints. Baseline NYHA was 3±0.6 despite medical therapy. Hemodynamic effects were assessed during pacing at RV apex and a mean of 8 LV sites (range 4-16). Optimal PPoP was achieved via LV pacing in 14 (88%) patients and RV apex in 2. Mean baseline gradient 80±29 mmHg fell to 31±21 mmHg with PPoP (p&lt;0.0001). Cardiac vein perforation occurred in one case, and 15 patients entered into cross-over; 2 withdrawals occurred during cross-over (myocardial infarction, persistent atrial fibrillation). Of the 13 completing cross-over, 9 (69%) chose active pacing as their preferred setting. PPoP was associated with better 6-minute walking test performance (329±100 vs 286±106 meters, p=0.018); other outcome measures also indicated benefit with PPoP. Conclusions: In a randomized placebo-controlled trial, PPoP reduces obstruction and improves exercise performance in severely symptomatic LVMCO patients. A personalized approach to pacing site selection is a key component of this novel therapy.
Abstract 167: Neutrophil Maturity Following Resuscitation From Cardiac Arrest
Authors: Joanne T deKay, Mary Weatherbee Sorcher, Teresa May, David Gagnon, Douglas B Sawyer, Richard Riker, David B. Seder, Sergey V Ryzhov
Journal: Circulation (2023)

Introduction: Immature neutrophils mobilized from bone marrow in response to injury do not express CD10 and are characterized as pro-inflammatory. Maturity status of neutrophils has not yet been described in patients after the global ischemic-reperfusion injury following cardiac arrest (CA). Hypothesis: Immature neutrophils predominate the systemic cellular response after CA and are associated with mortality. Goal: To characterize neutrophils and their associations with clinical parameters in patients following resuscitation from CA. Methods: After informed consent, 100 subjects were enrolled. Blood samples were collected at 6, 12, 24, 48, 72, and 168 hours after return of spontaneous circulation (ROSC). White blood cells (WBC) were isolated and stained for flow cytometry. Data analysis was performed with FlowJo and GraphPad Prism; a P-value of &lt;0.05 was deemed statistically significant. Results: In our cohort of 51 non-survivors and 49 survivors, there were no significant differences in WBC count at any time point. At 72 hours after ROSC, we found a higher absolute number (6.8 vs. 5.0; p=0.018) and percentage ( 87.1 vs. 80.3; p=0.030) of neutrophils in the WBC population in non-survivors compared to survivors. Analysis of neutrophil CD10 subpopulations revealed a higher number of immature CD10 - neutrophils in non-survivors at 72 hours after ROSC (6.1 vs. 4.4; p=0.007) compared to survivors. There was no significant difference between non-survivors and survivors in mature CD10 + neutrophil count or temporal changes. The CD10 - /CD10 + neutrophil ratio was significantly higher in non-survivors at 24 hours (4.7 vs. 3.1; p=0.036) and 48 hours (11.5 vs. 6.6; p=0.040) after ROSC. Conclusions: Neutrophils are important to inflammation resolution after injury; however certain subpopulations of immune cells may be involved in and perpetuate tissue damage after CA. The levels and temporal changes of pro-inflammatory, immature (CD10 - ) neutrophils in non-survivors point to the need for further research including functional studies. The identification of neutrophil marker targets that may impact the balance of pro- and anti-inflammatory immune cells and their related signaling pathways could offer opportunities to improve outcomes after cardiac arrest.
Abstract 13989: Automated VT Localization System Based on Patient-Specific Integration of Two-Dimensional (2D) Intracardiac Echocardiography (ICE) and 3DElectroanatomic (EA) Mapping
Authors: Shijie Zhou, Amir AbdelWahab, Ronald D Berger, Harikrishna S Tandri, Jonathan Chrispin, John L Sapp
Journal: Circulation (2023)

Introduction: We have previously developed an intraprocedural automated localization system to identify VT-exit sites projected onto a patient-specific CT geometry using 12-lead ECGs. However, the accuracy of the system depends on a registered reconstruction of the cardiac surface. Objective: To assess the feasibility of using a registered integration of 2D ICE and 3D EA mapping to perform intraprocedural localization, while avoiding errors being introduced by registration of the CT geometry and EA map. Methods: Four patients with 7 VTs (5 LV VTs, 2 RV VTs) were enrolled. A 3D patient-specific shell of both ventricles that combines ICE and EA map was reconstructed during the ablation procedure. It was imported into the automated localization system post-procedure for offline analysis. The system was used to estimate the location of VT-exit sites on the reconstructed 3D geometry. Localization accuracy was quantified for the VT-exit sites by comparing the distance of the calculated site to the site of successful ablation or that of best pacing site match. Results: Five reentrant VT-exit sites were identified using activation and entrainment mapping, supplemented by pace-mapping at the scar margin; two focal VTs were identified by pace mapping. The proposed system achieved mean localization accuracy of 6.4 mm for 7 VTs. Conclusions: ICE and EA mapping can be successfully integrated for intraprocedural automated localization of ventricular activation in both ventricular chambers and may avoid registration errors of CT geometry integration.