tbuckley/cabot-search huggingface dataset:
Abstract 13430: Cardiovascular Magnetic Resonance Imaging for Comprehensive Risk Assessment in Patients With Aortic Stenosis
Authors: Torben Lange, Bo Beuthner, Alexander Schulz, Soeren J Backhaus, Ruben Evertz, Karl-Rudolf Rigorth, Karl Toischer, Johannes T Kowallick, Gerd Hasenfuss, Miriam Puls, Andreas Schuster
Journal: Circulation (2023)

Introduction: Precise risk assessment is essential for accurate management of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). This study aimed to assess the prognostic implications of cardiovascular magnetic resonance (CMR)-derived imaging biomarkers in a large cohort of AS patients. Methods: 145 patients with severe AS underwent CMR imaging before TAVR. Image analyses included myocardial volumes, CMR-feature-tracking derived left and right atrial (LA &amp; RA) as well as left and right ventricular (LV &amp; RV) strain, myocardial T1 mapping as well as late gadolinium enhancement analyses. Cardiovascular (CV) mortality was defined as primary clinical endpoint. Results: Patients with CV death during follow-up had significantly enlarged RV enddiastolic volumes (82.9ml/ml 2 [70.8-96.0] vs. 62.8ml/ml 2 [54.7-76.0], p&lt;0.001) and impaired strain values of all cardiac chambers compared to patients that survived (LV GLS: -18.1% [-13.1- -20.4] vs. -22.5% [-16.1- -27.3], p=0.019; RV GLS: -22.9% [-18.6 - -25.4] vs. -27.9% [-22.9- -32.0], p=0.002; LA Es: 9.5% [7.2 - 15.4] vs. 14.3% [9.0-18.1], p=0.036; RA Es: 12.4% [6.8-14.4] vs. 16.2% [11.2-22.1], p&lt;0.001). RA reservoir strain independently predicted CV mortality after adjusting for other CMR imaging biomarkers and clinical parameters of heart failure. Within patients with high ECV values especially RA strain further identified AS patients at high-risk for CV mortality (p=0.001 on log-rank testing). Conclusion: Comprehensive CMR-imaging allows accurate outcome assessment and additional identification of high-risk groups in AS patients. Especially RA strain emerged as independent predictor for cardiovascular mortality and might serve for future optimized patient management.
Abstract 11624: Body Fat and Cardiometabolic Disease Burden in Adults With Normal Body Mass Index
Authors: zhuo chen, Jingen Li, Betsy Medina-Inojosa, Jose R Medina-Inojosa, Kyla Lara-Breitinger, Virend K Somers, Andres Acosta, Amir Lerman, Francisco Lopez-Jimenez
Journal: Circulation (2023)

Background: The role of body adiposity on metabolic dysregulation in subjects with normal body mass index (BMI) is still under debate with limited population-based evidence. Hypothesis: Body adiposity measured by dual x-ray absorptiometry (DEXA) is associated with metabolic disorders in normal-weight individuals. Methods: We evaluated a sample of adults aged 20-65 who underwent DEXA in the US National Health and Nutrition Examination Surveys from 1999-2006 and 2011-2018. We excluded those with history of cardiovascular disease, cancer, and chronic obstructive pulmonary disease. Weighted logistic regression was performed to test the association between body fat percentage (BF%) and metabolic disorders [e.g., insulin resistance (IR), metabolic syndrome (MS), dyslipidemia, type 2 diabetes mellitus (DM), hypertension]. Models were adjusted for potential confounders while considering complex survey design and were further stratified by sex and BF% as tertiles in normal-weight individuals. IR was tested as a secondary analysis to evaluate the effect on the predicted risk. Results: We included 20,613 individuals (51.5% men, 65.4% non-Hispanic whites), mean age ± SE was 39.42±0.22 years, and 6,424 were normal weight by BMI and represented our study sample. The overall BF% in these subjects measured by DEXA was 28.41±0.19%. In our cohort, metabolic disorders were prevalent in 2.1% to 40.4% of patients (Table 1). Every 10-unit % increase in total BF% was associated with a higher risk for IR, MS, dyslipidemia in the normal weight BMI group (Table 1). Metabolic disorders were associated with BF% tertiles (Figure 1). IR was significantly associated with body fat across all BF% tertiles for men and highest tertiles for women (Figure 2). Conclusion(s): Less than 1/3 of subjects in a representative national sample had a normal BMI. Even in these “normal weight” subjects, increases in body adiposity are significantly associated with increased cardiometabolic disease burden.
Abstract 14196: Prevalence of Ischemic and Nonischemic Sudden Cardiac Death Differs by Sex and Age
Authors: Anette Eskuri, Juha Vahatalo, Lasse Pakanen, Lauri Holmstrom, Juha Perkiomaki, Heikki Huikuri, Juhani Junttila
Journal: Circulation (2023)

Introduction: During the last decades the proportion of nonischemic sudden cardiac death (NI-SCD) seems to have increased in both sexes. In women the incidence of coronary artery disease (CAD) starts to increase after the menopause. Aim: The aim of this study was to illustrate how the amount and the proportions of ischemic SCD (I-SCD) and NI-SCD vary between women and men in different age groups. Methods: The Fingesture study consists systemically collected clinical and autopsy data of 5,869 SCD victims of Northern of Finland (21% women). Results: In women 6.7% of the SCDs occurred at the age &lt; 50 years and in men 11.4% (P&lt;0.001 for both). I-SCDs covered 75% (P&lt;0.001) of the cases of which 80% were men (P=0.005). The proportion of NI-SCDs was higher in women in every age group. Proportion of I-SCDs started to increase rapidly in both sexes at the age of 40-44 years. In women aged 50-54 years 53% of the cases were I-SCDs. The gender difference in proportion of I-SCD was actually the smallest in age groups 40-49 years and after 70 years of age, and its largest in the middle in favor of men. (Figure 1). After the age of 70 years the total amount of SCDs started to plateau in men and decrease in the amount of SCDs was seen in men after the age of 75 years as in women the plateau phase was not reached until the age of 80 years (Figure 2). Conclusions: Minority of the SCDs occur under the age of 50 years, especially in women. The proportion of NI-SCD was higher in women than in men despite the age but the proportion of I-SCD was remarkable already at pre- and perimenopausal age. The amount of I-SCD increased in women until the age of 80 years emphasizing the need of early primary and secondary prevention of CAD also in women not only in men.
Abstract 18657: Diagnostic Yield of Whole Genome Sequencing in Congenital Heart Disease: Data From the UK 100,000 Genomes Project
Authors: Stephanie L Baross, Simon G Williams, Kathryn E Hentges, Bernard D Keavney
Journal: Circulation (2023)

Congenital heart disease (CHD) is the most common birth defect affecting around 1% global live births. The aetiology of CHD is poorly understood: while a number genetic loci have already been identified, the majority of cases remain unexplained. Many CHD cases occur with additional abnormalities, or as part of a defined syndrome (eg. Noonan or CHARGE syndromes). The 100,000 Genomes Project conducted whole genome sequencing for patients with a range of rare diseases and cancers in partnership with the UK National Health Service. We analysed clinical and genetic data from the project in 2638 participants with CHD, including both primary CHD cases and secondary cases who have CHD as part of a syndromic presentation but were recruited under other disease categories. Both cohorts are primarily composed of patients with CHD accompanied by additional extra-cardiac abnormalities without a prior diagnosis of a defined syndrome. We found that families recruited as primary CHD cases were significantly less likely to have been classed as “solved cases” (indicating a pathogenic variant has been identified) than phenotypically similar secondary CHD cases (5.4% primary, 16.2% secondary; p = 6.78х -11 ). This is primarily due to differences in the gene lists used in analysis, with the majority of diagnoses in both groups due to genes not included in the CHD gene panel (83% primary and 97% secondary cases). Expanding standard CHD screening to include a wider range of syndromic CHD genes is likely to increase the diagnostic yield for the primary CHD cohort by more than two-fold. Copy number variants (CNVs) also contribute to CHD, especially in cases with additional abnormalities. CHD cases have a significantly higher burden of both deletions (p = 1.00х10 -5 ) and duplications (p = 0.009) than an ethnically-matched control cohort. However, only 7 of 2638 participants have CNVs in known CHD-causative regions such as the 22q11.2 or Williams-Beuren syndrome regions indicating novel CNVs are likely to contribute to a significant number of cases. Wider screening of syndromic CHD genes and novel copy number variants is likely significantly increase the diagnostic yield for CHD both within the 100,000 Genomes Project and in healthcare settings, and potentially yield novel CHD-associated loci.
Abstract 12010: Duration of Postoperative Atrial Fibrillation After Coronary Artery Bypass Graft Surgery is Associated With Poor Perioperative Outcomes
Authors: Haokai Qin, Enzehua Xie, Zhan Peng, Xiubin Yang, Kun Hua
Journal: Circulation (2023)

Background: Postoperative atrial fibrillation (POAF) is one of the most common complications after coronary artery bypass graft surgery (CABG). It has long been associated with poor perioperative outcomes, but few studies have been carried out regarding the effect of POAF duration on those outcomes. Research Questions: Does prolonged duration of POAF have an adverse effect on perioperative outcomes of CABG? Methods: This retrospective cohort study examined CABG patients enrolled at Beijing Anzhen Hospital from January 2018 to September 2021. We compared POAF duration ≥48 hours patients with POAF duration &lt;48 hours patients. Primary outcomes examined were in-hospital mortality, stroke, acute respiratory failure (ARF), acute kidney injury (AKI), as well as significant gastrointestinal bleeding (GIB); secondary outcomes were postoperative length of stay (LOS), intensive care unit (ICU) stay. Associations between primary outcomes and POAF duration were determined using logistic regression and restricted cubic spline analyses. Results: Out of 11 848 CABG patients, 3604 (30.4%) had POAF; 1131 (31.4%) of POAF patients had it for duration ≥48 hours. ARF (adjusted odds ratio [OR]: 2.96, 95% confidence interval [CI]: 1.47 - 6.09), AKI (adjusted OR: 2.37, 95% CI: 1.42 - 3.99), and significant GIB (adjusted OR: 2.60, 95% CI: 1.38 - 5.03), but not in-hospital mortality (adjusted OR: 1.56, 95% CI: 0.92 - 2.65) or stroke (adjusted OR: 1.29, 95% CI: 0.70 - 2.33) was associated with POAF duration ≥48 hours. These findings were still applicable, even after conducting propensity score matching and inverse probability of treatment weighting analyses. Conclusions: POAF duration longer than 48 hours was independently associated with poorer perioperative recovery from CABG, with respect to the occurance of AFR, AKI and GIB, as well as longer postoperative LOS and ICU stay. However, it was not associated with greater in-hospital mortality or stroke occurrence. All these findings suggest that postoperative monitoring of POAF and positive intervention after detection could optimize post-CABG patient outcomes.
Abstract 13490: Sex Differences in the Association of Multi-Ethnic Genome-Wide Blood Pressure Polygenic Risk Score With Population Systolic Blood Pressure Trajectories
Authors: Naman Shetty, Akhil Pampana, Nirav Patel, Krishin Yerabolu, Gnyata Patel, Marguerite Irvin, Pradeep Natarajan, Henry J Lin, Xiuqing Guo, Stephen S Rich, Jerome I Rotter, Li Peng, Garima Arora, Pankaj Arora
Journal: Circulation (2023)

Introduction: Sex differences in the systolic blood pressure (SBP) trajectories have been described previously. However, the contribution of underlying genetic architecture to the sex associated differences in SBP trajectories has not been assessed. Methods: Multiancestry sex-specific SBP polygenic risk scores (SBP-PRS), accumulating 1.1 million variants each, were calculated in the participants of the ARIC, JHS, CARDIA, CHS, MESA, FHS, and JHS who underwent whole genome sequencing under the TransOmics for Precision Medicine Program. Based on the SBP-PRS, the cohort was stratified into low (&lt;20 th centile), intermediate (20 th -80 th centile), and high (&gt;80 th centile) genetic risk of SBP. For individuals on antihypertensive medications, SBP measurements were corrected by adding 15 mmHg. Multivariable adjusted restricted cubic splines were used to depict the non-linear relationship of SBP with age in each sex separately. Bootstrapping using 1000 samples was used to estimate the age and 95% CIs at which the sex-specific SBP trajectories crossed over in each SBP-PRS group. Results: In this study of 21,542 individuals (median age: 56 years; 56.0% females; 35.8% non-White individuals), the non-linear association of SBP with age varied by sex (P interaction : &lt;0.001) and SBP-PRS groups (P interaction : 0.05). On stratifying by SBP-PRS, females had a higher age-related increase in SBP compared with males across the groups (p&lt;0.001 in low, intermediate, and high SBP-PRS groups). The age at which the SBP in females surpassed that of males progressively decreased with increasing genetic risk of SBP [low: 66.7 (66.4-67.0) years, intermediate: 64.3 (64.1-64.6) years, high: 55.8 (54.4-57.1) years; p: &lt;0.001]. In the high SBP-PRS group, the sex-associated differences in SBP trajectories were modest with females and males having nearly similar SBP values in old age. Conclusion: The underlying genetic architecture may contribute to sex difference of SBP trajectories.
Abstract 15853: Long-Term Outcomes of Young Patients With Chest Pain and Normal Epicardial Coronary Arteries: A 10-Year Prospective Study
Authors: Mohammadreza Naderian, Seyedmohammad Saadatagah, Alireza Ramandi, Kian Alipasandi, Hamidreza Pourhosseini, saeed sadeghian
Journal: Circulation (2023)

Introduction: Long-term outcomes of young patients with chest pain and normal epicardial coronary arteries (NECA) in angiography remain understudied. Methods: We conducted a prospective study in a tertiary heart hospital between 2004-2020, enrolling men&lt;45 and women&lt;55 years presenting with symptoms or objective findings of coronary artery disease (CAD) and confirmed NECA in angiography. Patients with cardiomyopathy, coronary anomaly, and significant valvular, renal, pulmonary, or liver diseases were excluded. The primary outcome was MACCE, defined as the composite of death, CCU admission (for MI or unstable angina), stroke, and revascularization. Follow-ups were done every 5 years using a standardized questionnaire and a committee of experts reviewed all the events. Expected age and sex-adjusted mortality rates were estimated using national data. The association between exposures and MACCE was studied using multivariable Cox-proportional hazard models. Results: 1257 patients, 340 (27.05%) men (38.34±5.46 years), and 917 (72.95%) women (48.41±4.94 years) were included. 698 (55.53%) had acute and 559 (44.47%) had chronic symptoms. Over the median 9.4 (8.5-11.0) years of follow-up, 134 (10.66%) events happened. CCU admission (6.33%) was the most common event (Figure). The 10-year mortality rate (per 100,000-person-years) was 265 for men and 174 for women, which were 1.6 and 2.5 times higher than the age-sex-matched rate of the normal population, respectively. Diabetes, hypertension, and presenting with acute symptoms were associated with higher MACCE with the hazard ratios (95% CI) of 1.87 (1.05-3.31, P:0.03), 1.72 (1.13-2.61, P:0.01), and 1.56 (1.03-2.36, P:0.04), respectively. During follow-up, 192 (15.27%) repeated angiographies were done and 19.8% developed obstructive CAD. Conclusions: In young patients with chest pain and NECA, approximately 10% experienced MACCE during a 10-year follow-up, and the mortality is higher than expected.
Abstract 197: Establishing a Novel Pulse Wave Velocity-Guided Mouse Model of Cardiac Arrest With Different Durations
Authors: zhen W zhuang, Fang Liu
Journal: Circulation (2023)

Background: Neurological and cardiovascular injuries are the leading causes of death following cardiac arrest (CA). Few rodent models recapitulate these post-resuscitation symptoms. Aims: To develop extended ischemic CA models under Pulse Wave Velocity ( PWV) guidance with consistent post-CA brain injury (PCABI) and coronary dysfunction as potential therapeutic targets and mechanical studies. Methods: Forty-eight mice were randomized into four experimental groups (control, 8-, 12-, and 16-min CA). Potassium chloride (KCL) was intravenously injected, resulting in immediate asystole. Mice were resuscitated with an injection of epinephrine and manual chest compressions. PWV was monitored for the left carotid artery velocity and coronary flow reserve (CFR). Resuscitability, synaptic density in the hippocampal CA1 region, blood-brain barrier (BBB), and neurologic deficit scores (NDS) were also evaluated. Results: The PWV could monitor rapid asystole after KCL injection, improve cardiopulmonary resuscitation (CPR) success rates, and avoid the pre-matured end of resuscitation. Compared to the standard control, mice with 8-min CA had preserved CFR, mild loss of synaptic density (p&gt;0.05), mild hypothermal, and a normal electrocardiogram. They maintained BBB integrity with no significant change to neurologic function. Compared with a 92% CPR success rate in 8 min-CA mice, 12 min-CA mice had 83%, and 16 min-CA mice had 58% resuscitability. Twelve min-CA mice had significantly impaired CFR at 24 hours and high lethality (40%, P&lt;0.05) within the first three days; 16 min-CA mice worsened (33% survival rate, p&lt;0.01). The 24 hrs electron microscope showed that CA-induced synaptic vesicle densities were ischemic time-dependent [350±60 (control) vs. 289±64 (8 min CA) vs. 269±34 (12 min CA) vs. 181±41/field (16 min CA)], consistent with NDS. The cerebrum and hippocampus were the most valuable regions, indicated by Evans blue evaluation at 48 hrs after CA. Conclusions: We established elongated PWV-guided CA models as with successful CPR, post-CA neurological deficits, leaky BBB, loss of synaptic density, coronary endothelial dysfunction, and even death in mice, which closely recapitulated the post-resuscitation symptoms in survived patients after CPR.
Abstract 16977: Determining Rates of Meaningful 30-day Health Status Changes Following Transfemoral Carotid Artery Stenting
Authors: Jonathan Kluger, Gaelle Romain, Jacob Cleman, Lindsey Scierka, Scott Grubman, Carmen S Pajarillo, Christopher Schenck, Kim G Smolderen, Carlos Mena-Hurtado
Journal: Circulation (2023)

Introduction: While carotid artery revascularization studies have focused on clinical endpoints such as death, MI, and stroke, few cover these treatments’ effect on health status. We previously established minimal clinically important differences (MCIDs) to assess clinical improvement or worsening in generic health status for patients undergoing transfemoral carotid artery stenting (TF-CAS) and aimed to use these to study the distribution of health status responders following TF-CAS. Methods: We studied patients in the multicenter Stenting and Angioplasty with Protection in Patients at High Risk for Endarterectomy (SAPPHIRE) registry who underwent TF-CAS between 2010 and 2014 and completed either the EQ-5D-3L or SF-36 (two generic health-related quality-of-life surveys) within the first 28 days before TF-CAS and 30 days after. Patients were classified as improving, worsening, or experiencing no change based on score changes relative to distribution-based MCIDs of 0.09 and 11.00 for the EQ-5D-3L index value and visual analog scale (VAS) subscales, respectively, and 4.70 and 5.40 for the SF-36 mental and physical component summaries (MCS and PCS), respectively. We then stratified both cohorts by symptom status, defining symptomatic patients as having symptoms suggesting prior stroke or TIA. Results: This study included 3,930 patients (27.74% symptomatic) who completed the EQ-5D-3L and 3,018 (30.45% symptomatic) who completed the SF-36. For the full cohorts across the four subscales, 21.17%-26.11% improved, 10.53-16.67% worsened, and 57.22-66.06% experienced no change. The distributions of changes in scores by symptom status overlapped significantly (Figure 1). Conclusions: Roughly 20-25% of patients, regardless of symptom status, improved in terms of generic health status following TF-CAS, while about 70-80% worsened or experienced no change. Disease-specific instruments would further elucidate the effect of TF-CAS on patients' health status.
Abstract 14204: Efficacy and Safety of Low-Dose Edoxaban According to Body Weight in Very Elderly Patients With Atrial Fibrillation: A Sub-Analysis of the ELDERCARE-AF Trial
Authors: Masaharu Akao, Takeshi Yamashita, Masayuki Fukuzawa, Takuya Hayashi, Ken Okumura
Journal: Circulation (2023)

Background: The ELDERCARE-AF trial showed that low-dose edoxaban is beneficial in elderly patients with non-valvular atrial fibrillation (AF) who are considered ineligible candidates for standard oral anticoagulants (OACs) due to high bleeding risk, but it was not known whether this is the case in low-body-weight patients. Methods: This was a prespecified sub-analysis, by body weight (≤45 and &gt;45 kg), of the ELDERCARE-AF trial, a randomized, placebo-controlled trial comparing low-dose edoxaban (15 mg once daily) with placebo. All patients were of Japanese ethnicity and considered ineligible for standard doses of OACs. The primary efficacy endpoint was stroke or systemic embolism (SSE). The key secondary endpoints were all-cause mortality and net clinical outcome. The primary safety endpoint was major bleeding according to the definition of the International Society on Thrombosis and Hemostasis. Results: Of the 984 patients, 374 patients (38.0%) were in the ≤45 kg group and 610 (62.0%) patients were in the &gt;45 kg group. The SSE was lower with edoxaban than with placebo in both weight groups (≤45 kg group: hazard ratio [HR] 0.36, 95% confidence interval [CI] 0.16-0.80; &gt;45 kg group: HR 0.31, 95% CI 0.13-0.73; interaction P 0.82). Both all-cause mortality and net clinical outcome were higher in the ≤45 kg group, with no significant difference between treatment groups. Major bleeding was numerically higher with edoxaban than with placebo (≤45 kg group: HR 3.05, 95% CI 0.84-11.11; &gt;45 kg group: HR 1.40, 95% CI 0.56-3.48), with no interaction with body weight (interaction P 0.33). Similar results were obtained in the exploratory analysis of patients divided into four quartiles of body weight (&gt;57.9, &gt;49.0 to ≤57.9, &gt;42.0 to ≤49.0, and ≤42.0 kg). Conclusions: The benefit of edoxaban 15 mg was consistent in elderly AF patients with low body weight, provided clinicians remain vigilant about the risk of major bleeding.