tbuckley/cabot-search huggingface dataset:
Abstract 4135061: Myocardial work in different patients with electrical dysynchrony due to left bundle branch block
Authors: Elena Rimskaya, Dobrovolskaya Svetlana, Elizaveta Kukharchuk, Svetlana kashtanova, Nataliia Mironova, Alexey Komlev, Timur Imaev, Gennadiy Tarasovskiy, Marina Saidova, Sergey Golitsyn
Journal: Circulation (2024)

Left bundle branch block (LBBB) in patients with dilated cardiomyopathy (DCM) is defined by huge wasted work and decreased myocardial constructive work. The aim of this study is to assess the myocardial work in patients in LBBB and other clinical situations. Materials and methods: The echocardiographic study was performed in 25 patients with LBBB and DCM (LBBB-DCM); 20 patients with DCM and narrow QRS complex (nonLBBB-DCM group); 15 patients with LBBB developed after transcatheter aortic valve implantation (TAVI group); 12 patients with idiopathic LBBB, normal systolic LV function and excluded cardiovascular pathology (LBBB group); 27 patients with right ventricular pacing due to atrioventricular block of high grade (RVP group) and 20 healthy volunteers (HV group). In all of them global longitudinal strain (GLS) and myocardial work parameters including global constructive work (GCW), global wasted work (GWW), global work index (GWI) and global work efficiency (GWE) were assessed. In all patients the segments with maximum and minimum GWI value were determined. Results: GLS, GWI and GCW values were comparable in LBBB and RVP groups, whereas in TAVI and in both DCM groups they was significantly lower than in HV (p = 0.049, 0.006, 0.025; p &lt; 0,001 respectively, (Fig.1A,B,C)). Patients from LBBB, TAVI, RVP and LBBB-DCM groups were characterized by increased amount of GWW (261 [203.5; 291.5], 273 [184.8; 385,3] and 237 [149.5; 445.3] vs 108 [74.3; 137.3] mmHg%, p = 0.033, 0.006, &lt; 0.001, &lt; 0.001 respectively). GWW value in LBBB-DCM group was the highest (346.5 [255.5; 437.8] mmHg% (Fig.1D). There was moderate strength of relation between GWW and QRS duration (ρ=0.456, p&lt;0.001). A huge amount of wasted work affected the GWE value and led to its considerable reduction in LBBB, TAVI, RVP and LBBB-DCM groups compared to HV (p = 0.033, 0.007, 0.023, &lt; 0,001, respectively, Fig.1E). The zone of maximum GWI localized in posterolateral wall, the zone of minimum GWI was in interventricular septum in most LBBB patients (Fig.1F). At the same time, these zones turned out to be very variable in RVP group. Conclusion: Although all patients with LBBB pattern of electrical activation are characterized by significant amount of wasted work, its contribution to global myocardial work manifested only in DCM patients. Wasted work doesn’t lead to reduced constructive work in patients with idiopathic LBBB and RVP and normal systolic function probably due to compensatory mechanisms.
Abstract 4134655: Clinical Outcomes of Patients with Alcoholic Cirrhosis and Acute STEMI Undergoing PCI
Authors: Zaid Alwarawrah, Nmair Alziadin, saleh alhalaseh, Barbara Odac, Husam El Sharu, Omar Al
Journal: Circulation (2024)

Original research: Background: The objective is to evaluate the outcomes of percutaneous coronary intervention (PCI) in patients with alcoholic cirrhosis presenting with ST-segment elevation myocardial infarction (STEMI). Methods: We analyzed data from the National Inpatient Sample (NIS) for the years 2016-2020. Our cohort included patients admitted with STEMI and a secondary diagnosis of alcoholic cirrhosis, excluding those under 18 or those not receiving PCI. Propensity score matching using a kernel method was applied to adjust for 22 variables, including patient demographics, hospital characteristics, and comorbid conditions. Results: Among 119,799 patients, 98 had alcoholic cirrhosis. These patients exhibited higher mortality (18% vs. 5%) and longer hospital stays (5.4 days vs. 3.6 days). They also had increased risks of acute blood loss anemia (13% vs. 3.5%) and gastrointestinal bleeding (18% vs. 2%). Additionally, acute kidney injury was more prevalent in the cirrhosis group (25.5% vs. 14%). Although heart failure exacerbation and cardiac arrhythmias were more common, these were not statistically significant (Table 1). Conclusion: Our study indicates a significantly higher mortality rate among patients with alcoholic cirrhosis undergoing PCI for STEMI. These patients are also at increased risk of postoperative bleeding due to compromised liver function and hemostatic abnormalities, as reflected by higher incidences of acute blood loss anemia and gastrointestinal bleeding. Additionally, there is an elevated risk of acute kidney injury post-PCI, highlighting the need for renal-protective strategies. These findings stress the necessity for specialized care, vigilant monitoring, and tailored protocols to address the unique challenges faced by this population, aiming to reduce morbidity and mortality.
Abstract 4137964: Electrical Gaps and Outcomes After Redo AF Ablation: Comparative Analysis from the EARNEST-PVI Trial
Authors: Masato Okada, Nobuaki Tanaka, Koji Tanaka, Yuko Hirao, masaharu masuda, Tetsuya Watanabe, Koichi Inoue, Shungo Hikoso, Akihiro Sunaga, Daisaku Nakatani, Yohei Sotomi, Yasushi Sakata
Journal: Circulation (2024)

Introduction: The efficacy of extensive ablation strategies in addition to pulmonary vein (PV) isolation is still controversial in persistent atrial fibrillation (AF) ablation. Gaps in previously ablated lesions can induce arrhythmias, potentially decreasing the effectiveness of extensive ablation. Purpose: To evaluate the incidence of gaps, gap-related reentry, and subsequent recurrence following redo AF ablation in the EARNEST-PVI trial (NCT03514693). Methods: The analysis was performed using the extended data of the EARNEST-PVI trial (N=512), a randomized controlled trial evaluating ablation strategies for persistent AF. Patients were randomized 1:1 to either the PVI-plus or PVI-alone group. During a median follow-up of 47 months, 126 (25%) patients underwent redo AF ablation. Among them, we enrolled patients who underwent PVI-alone (N=69), or PVI-plus left atrial (LA) linear ablations (LA roof and mitral isthmus) (N=46) during the index ablation. Results: In the previous PVI-alone group, electrical PV gaps were observed in 38 (57%) patients. In the previous PVI-plus group, 19 (41%), 10 (22%), and 11 (24%) patients had electrical gaps in the PVs, LA linear lines, or both, respectively. During the redo session, 19 atrial tachycardias (ATs) were observed/induced in 15 patients. ATs were more frequently observed in the PVI-plus group than in the PVI-alone group (23.9% vs. 5.8%, p=0.005). While 7 ATs were not associated with gaps, 2 were related to PV gaps, and 10 were related to gaps in the linear lesions. In the redo AF ablation, PVI was re-completed in all patients, and any induced ATs were eliminated by additional ablation. During a median follow-up of 32 months post-redo, patients with gaps had a lower clinical recurrence rate than those without (44.3 vs. 47.2%, log-rank p=0.033). However, the Cox regression analysis revealed that AF recurrence post-redo was associated only with PV gaps, and not with linear ablation gaps (hazard ratio, 0.57; 95% confidence interval, 0.32–0.99; p = 0.049). Conclusions: In redo AF ablations, electrical gaps were more prevalent in patients who underwent extensive ablation during the index procedure. While all gaps during redo were potentially arrhythmogenic, PV gaps alone were associated with AF recurrence after redo AF ablation.
Abstract 4137364: Sex differences in the right ventricle in the Sugen-Hypoxia rat model of pulmonary arterial hypertension
Authors: Chelbi Coyle, Margaret MacLean, Lian Tian
Journal: Circulation (2024)

Background: An unexplained estrogen puzzle exists in pulmonary arterial hypertension (PAH): PAH occurs ~4 fold more frequently in women than men; however, women with PAH have better right ventricular (RV) function and survival than the men. Sex differences and the associated mechanism in RV in PAH are not well understood. Aim: To characterize sex differences in RV function and structure in PAH. Methods: Sprague-Dawley rats were injected with Sugen (SU5416, 25mg/kg), and subjected to 3 weeks of hypoxia, followed by 5 weeks of normoxia. Control rats received vehicle and stayed in normoxia for up to 8 weeks. RV pressure-volume, mitochondrial properties, weight, myocyte size, cell proliferation, and interstitial and perivascular (right coronary arteries, RCA) fibrosis were obtained. Results: Sugen-Hypoxia (SuHx) caused significant increases in RV systolic pressure (RVSP) and effective arterial elastance (Ea) in both sexes (P&lt;0.05), but caused slightly greater increase in RV end-systolic elastance (Ees) in females vs males, leading to a preserved RV-pulmonary artery coupling (Ees/Ea) in females and a significant decrease in Ees/Ea in males (P&lt;0.05). SuHx caused a significant increase in RV diastolic pressure only in males (P&lt;0.05), which is associated with significantly higher amount of RV interstitial fibrosis in males vs females. In addition, SuHx caused significant increase in cell proliferation in both sexes (P&lt;0.05) though with slightly greater in crease in males, which is well correlated with RV interstitial fibrosis. Whilst there was no sex difference in RV hypertrophy in SuHx rats as indicated by both fulton index and myocyte size, female RV had smaller myocytes than males at baseline, indicating a greater increase in myocyte size in response to SuHx. Finally, there was a significant increase in RCA fibrosis in male SuHx rats (P&lt;0.05) but not in females, potentially leading to a greater degree of ischemia in male SuHx RV, and this is consistent with impaired mitochondrial properties (decreased mitochondrial fusion, membrane potential an superoxide) in male SuHx rat RV (P&lt;0.05) but preserved mitochoindrial properties in females. Conclusions: SuHx resulted in similar level of RV afterload in both sexes, but compared to males, RV in females responded differently in both function (Ees and mitochondrial properties) and structure (myocyte size and fibrosis). Future studies on the associated mechanism are needed to gain therapeutic insight for RV in PAH.
Abstract 4135092: Prolonged Procedure Time and Its Association with Peri-Procedural Complications in Endovascular Therapy for Symptomatic Lower Extremity Arterial Disease
Authors: Taku Toyoshima, Osamu Iida, Yoshiharu Higuchi
Journal: Circulation (2024)

Background: Prolonged operative times in surgical procedures have been significantly associated with an increased risk of complications. However, the impact of prolonged procedure time of peri-procedural complications in patients undergoing endovascular therapy (EVT) for symptomatic lower extremity arterial disease (LEAD) has not been systematically evaluated. Aims: To determine the association between prolonged procedure time and peri-procedural complications in patients undergoing EVT for symptomatic LEAD. Methods: Data from a nationwide EVT registry in Japan (J-EVT) between 2021 and 2022 were analyzed. The outcome measure was peri-procedural complications defined as a composite of perioperative death, major bleeding, contrast nephropathy, myocardial infarction, ischemic stroke, and major amputation. Procedure time was categorized into four clinically relevant groups (≤59, 60–119, 120–179, and ≥180 minutes). The logistic regression model was developed to investigate the risk of peri-procedural complications across subgroups of procedure time with the shortest subgroup (≤59 minutes) set as the reference category. Results: A total of 47,301 patients (average age: 75±9 years, male: 69.0%, chronic limb-threatening ischemia [CLTI]: 51.0%) undergoing EVT for symptomatic LEAD were analyzed. Notable comorbidities included diabetes mellitus at 60.6% and dialysis at 29.9%, respectively. A history of coronary artery disease was noted in 40.7% of the participants. The median procedure time (interquartile range) was 110 (74–161) minutes. A total of 431 patients (0.9%) experienced perioperative complications. The perioperative complications included 48 deaths, 277 cases of major bleeding, 28 cases of contrast nephropathy, 10 myocardial infarctions, 16 ischemic strokes and 72 major amputations. After adjusting for patient and limb characteristics, and hospital and operator volumes, the odds ratios for perioperative complications were 1.21 (P=0.45) for 60–119 minutes, 2.36 (P=0.001) for 120–179 minutes, and 5.31 (P&lt;0.001) for ≥180 minutes with the shortest subgroup (&lt;59 min) set as the reference. Conclusions: Prolonged procedure time of EVT for symptomatic LEAD was significantly associated with an increased risk of perioperative complications.
Dose Modifications in the Management of Chronic Phase Chronic Myeloid Leukemia: Who, What, and When
Authors: Vivian G. Oehler, Ivan J. Huang, Chloe Siu, Miryoung Kim, Jessie Signorelli, Christopher S. Bell, Gabriela S. Hobbs
Journal: Journal of the National Comprehensive Cancer Network (2024)

With the availability of BCR::ABL1 targeted tyrosine kinase inhibitors (TKIs), outcomes for most individuals with chronic phase chronic myeloid leukemia (CP-CML) are outstanding, with life expectancy similar to age-matched peers. Treatment-emergent adverse events (TEAEs) impair quality of life and many patients struggle with low-level chronic AEs, which for some individuals impact emotional well-being as well as social and work functioning. An emerging body of data supports that many TEAEs are related to therapy dose and can improve with dose reduction. However, it is critical that dose reductions do not alter current outcomes, especially in the rare patients who are at greater risk of losing response or transforming to acute leukemia. Organizations including the National Comprehensive Cancer Network have begun to address when dose reductions may be considered in patients with CP-CML. In this manuscript, we review retrospective and prospective data reporting outcomes in patients after dose reduction and review data supporting lower dose preemptive dosing in first-line and later-line therapy. Switching therapy for intolerance can result in improvements in symptoms and limit toxicity, but other TEAEs may occur. Additionally, emerging therapeutics such as the new class of BCR::ABL1 allosteric inhibitors are under evaluation with a goal of improving tolerability. However, with many TKIs on the cusp of becoming generic, dose reduction becomes an appealing and important cost-effective strategy to minimize TEAEs and improve quality of life while preserving outstanding outcomes in CP-CML.
Abstract 4135023: Effect of mild hepatic impairment on the pharmacokinetics of pelacarsen
Authors: Jing-He Yan, Amanda Taylor, Timothy Clough, Elise Burmeister-Getz, Marketa Pazdirkova, Cesare Russo
Journal: Circulation (2024)

Introduction: Pelacarsen, a hepatocyte-directed, N-acetyl galactosamine (GalNAc 3 )–conjugated antisense oligonucleotide, reduces plasma lipoprotein(a) levels by inhibiting apolipoprotein(a) translation. Pelacarsen uptake is mediated by GalNAc 3 binding to the hepatocyte-specific asialoglycoprotein receptor. Hypothesis: It is unknown whether hepatic impairment (HI) impacts pelacarsen uptake and systemic exposure. Aim: This single-dose, open-label, parallel-group, Phase 1 study (NCT05026996) assessed the pharmacokinetics (PK), safety, and tolerability of a single 80 mg subcutaneous dose of pelacarsen in participants with mild HI compared to healthy controls (normal hepatic function). Methods: Eight adults with prior liver cirrhosis and mild HI (Child-Pugh Class A) were matched for sex, age, and body weight with nine healthy controls. PK parameters (C max , AUC 0-72, AUC last , and AUC inf ) were determined using non-compartmental methods. Log-transformed PK parameters were analyzed using a statistical model with group and matching covariates as fixed effects. Least-square geometric means for each group and geometric mean ratios between participants with mild HI and healthy controls were extracted. Safety was also assessed. Results: Pelacarsen C max , AUC last, and AUC inf were, on average, 7%, 37%, and 50% higher, respectively, in participants with mild HI versus matched controls. All 90% confidence intervals around the HI versus healthy control geometric mean ratios included 1 ( Table ). The ranges of all PK parameters and estimated half-lives were similar between groups. In participants with mild HI, pelacarsen exposure approached the same level as controls after eight hours post-dose ( Figure ). No serious adverse events occurred. Conclusion(s): In participants with mild HI, pelacarsen was well tolerated. Mild HI had no significant effect on pelacarsen C max . The non-statistically significant transient increase in AUC was within the exposure range tested in the first-in-human study.
Abstract 4133488: Persistent Disparities in Chronic Ischemic Heart Disease-Related Mortality across Age, Sex, Race/Ethnicity in the United States, 1999 - 2020
Authors: Patrick Kwaah, Samuel Mensah, Grace Appah, Abraham Carboo, Amoafo Boampong, Stephen Nii-Ashie Djanie, Ama Owusuaa Kwakye, Emmanuel Ababio Agyemang, Joseph Kekrebesi, Webster Donaldy, Patrick Nti
Journal: Circulation (2024)

Background: Chronic Ischemic Heart Disease (CIHD) is a heterogeneous group of cardiac diseases that cause significant morbidity and mortality. Previous studies demonstrated a decline in CIHD mortality rate (MR) but there is paucity of data on contemporary trends across different demographics in the United States (US). We examined the national trends in age-adjusted CIHD-MR (overall and stratified by demographics) in the US from 1999 to 2020. Methods: We retrospectively analyzed national death certificate data from the CDC WONDER database from 1999 to 2020. The underlying cause of death from CIHD was identified with ICD-10 code I25 in adults aged ≥35 years and the age-adjusted mortality rate was calculated per 100,000 population. We categorized race/ethnicity as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Latino or Hispanic, and other non-Hispanic groups. Trends in age-adjusted CIHD-MR (AAMR) were analyzed by age, gender, race/ethnicity, and geographic region were evaluated with Joinpoint regression, and expressed as an average annual percentage change (AAPC) with a 95% confidence interval. For sensitivity analysis, we repeated the study with data from death certificates that had CIHD as a contributing cause of death. Results: Out of 3.55 billion people aged ≥ 35 years, 5,985,088 died of CIHD (AAMR: 158.2 per 100, 000) [53.9% male, 81.6% NHW, 38.8% ≥85 years]. The AAMR was highest in males, the Northeast region, and NHB (Table 1). The AAMR was highest in those aged ≥85 years and was directly related to age (35-44 years: 8.3 per 100,000; ≥85 years: 1,943 per 100,000). The CIHD AAMR declined significantly overall in males, all races/ethnicities, and geographical areas (Table 1). Reanalysis (Sensitivity analysis) with any mention of CIHD as a contributing cause of death showed similar trends. Conclusion: Over the 22 years, CIHD-related mortality in the US has declined overall and for almost all demographic groups. However, there are age, gender, and racial disparities in the CIHD AAMR. These findings highlight the need for further longitudinal studies to understand the drivers of these disparities and for focused public health interventions to improve CIHD mortality outcomes in these populations.
Abstract 4134990: Body Fat Quantitation Predicts Progressive Cardiac Dysfunction with Age: Sex-Dependent Variations And Clinical Outcomes
Authors: Haowen Jiang, JIE JUN WONG, Glades Tan, Loon Yee Teo, See Hooi Ewe, Ru Tan, Fei Gao, Angela Koh
Journal: Circulation (2024)

Background: Among older adults whose body mass index (BMI) readings may be spuriously reduced due to loss of skeletal muscle, BMI alone may lack specificity for body fat quantitation. In addition, sex-based hormones differentially influence body fat composition between the sexes with aging. To evaluate the cardiometabolic effect of body fat on older adults, we hypothesize that sex would exert differential effects on baseline and progression of cardiac dysfunction in older adults. Methods: Community older adults without cardiovascular disease (CVD) underwent prospective transthoracic echocardiography with simultaneous body fat quantitation (body fat mass (BFM), percentage body fat (PBF), and waist-hip ratio (WHR) by bioimpedance, at baseline and five-year intervals. Mitral early diastolic inflow velocity to early diastolic annular tissue velocity (E/e') and early to late diastolic inflow velocity (E/A) ratios were recorded. Multivariable regression models were adjusted for significant clinical variables. Adverse clinical outcomes were defined as mortality or hospitalization during follow-up. Results: Baseline and interval annotation of 409 older adults (mean age 61±12.7 years, 52% females) demonstrated deteriorations in E/A ratios of -0.1 ± 0.3 and E/e' ratios of 1.8 ± 2.8, over a mean duration of 4.9 ± 0.4 years. Baseline BFM (β -0.01, p&lt;0.001; β 0.023, p=0.352) and PBF (β -0.008, p=0.002; β -0.007, p=0.759) predicted interval changes in E/A but not E/e' respectively independent of covariates (Table 1). In sex-specific analyses, higher baseline PBF was associated with deteriorations in E/A (β 0.010, p=0.028) among women and E/e' among men (β -0.069, p=0.020). Increases in PBF over time were particularly associated with reductions in E/A among women (β -0.005, p=0.047) independent of higher baseline PBF, in addition to significant interactions between sex and PBF in predicting changes in E/A. (Figure 1). Higher baseline WHR predicted adverse clinical outcomes [w1] among women (HR 1.09, 95%CI 1.03-1.16, p=0.005). Conclusion: Baseline and longitudinal increases in fat quantity defined a trajectory of deteriorations in cardiac function among older adults, and prognosticated poorer future outcomes, particularly among women with central adiposity as represented by WHR. Refining CVD risk based upon quantitative sex-specific fat targets for older adults may be a strategy in the future.