tbuckley/cabot-search huggingface dataset:
Abstract 4144238: Associations of neutrophil counts with risk of cardiovascular disease and all-cause and cause-specific mortality: a systematic review and meta-analysis of prospective cohorts
Authors: Cheng Wei, Bohao Tan, Ziyue Li, Yu Feng, Kang Wang, Bilian Yu, Yuchan Mou, Wichor Bramer, Shenghua Zhou, Zhangling Chen
Journal: Circulation (2024)

Background and Aims: High neutrophil counts, an easily accessible inflammation biomarker, has been linked to risk of cardiovascular disease (CVD), and mortality, but with mixed results. We aimed to summarize published associations between neutrophil counts with risk of CVD and all-cause and cause-specific mortality among generally healthy populations. Methods: We searched Medline, Embase, Web of Science, and Cochrane CENTRAL databases until March 2024. Random effect meta-analysis was conducted to calculate pooled risk ratios (RRs) and 95% confidence intervals (95%CIs) for highest versus lowest categories of neutrophil counts in relation to risk of CVD and all-cause and cause-specific mortality among general healthy populations. Linear and non-linear dose-response analyses were also performed. Results: Our systematic review and meta-analysis included 22 prospective cohort studies. During a median/mean follow-up period of 3.8 to 18.3 years, 73,934 CVD events and 80,317 deaths occurred among 1,962,191 participants. Higher neutrophil counts were associated with a higher risk of CVD incidence and all-cause mortality, CVD mortality, and non-CVD mortality. The pooled RRs (95%CIs) of highest versus lowest categories of neutrophil counts were 1.32 (1.20, 1.45) for risk of CVD incidence, 1.61 (1.23, 2.11) for all-cause mortality, 1.71 (1.45, 2.01) for CVD mortality, and 1.68 (1.17, 2.40) for non-CVD mortality. Further, per 1 SD increase of neutrophil counts was associated with a 4%, 12%, 14%, and 24% higher risk for CVD events, all-cause mortality, CVD mortality, and non-CVD mortality, respectively. In addition, a secondary dose-response analysis revealed a non-linear association of neutrophil counts with risk of CVD events (P non-linearity = 0.01), but a linear positive association with CVD mortality (P non-linearity = 0.87). The pooled associations of neutrophil counts with CVD risk, and all-cause, CVD, and non-CVD mortality did not differ by age, sex, region, and follow-up duration. Conclusions: Higher neutrophil counts were associated with a substantially higher risk of CVD events and all-cause, CVD, and non-CVD mortality.
Abstract 4144253: Sotagliflozin Reduces Contractile Work In Human Living Myocardial Slices
Authors: REBECCA TAICHMAN, Julia Smolyak, Kenneth Bedi, Sapna Patel, Kenneth Margulies, Sharlene Day, Benjamin Lee
Journal: Circulation (2024)

Introduction: Sodium glucose co-transporter inhibitors (SGLTi) are a class of medication with clinical benefit in heart failure regardless of subgroup. It has been postulated that SGLTi may have direct effects on the heart in addition to known systemic effects. One potential cardioprotective mechanism of SGLTi is through direct modulation of cardiac tissue mechanics, which few studies have investigated. New tissue slice platforms offer the potential to test impact of compounds on contractility but have not been fully validated. We sought first to establish the ability for human living myocardial slices (LMS) to recapitulate known disease-related and drug-related effects on biomimetic work loop parameters. We then assessed whether SGLTi directly and acutely affect LMS contractility. Methods: Vibratome-generated 300µm-thick slices of left ventricular tissue from non-failing donor hearts (N=10), failing hearts (N=4), and hypertrophic cardiomyopathy (HCM) septal myectomy tissue (N=7) were adhered to 8x8mm anchors and mounted onto the IonOptix Cardiac Slice System. We generated force-length work loops at varying preloads (4-16% strain) and afterloads (25-75% active force). Drug (sotagliflozin 10µM, isoproterenol 5µM, mavacamten 1µM) or vehicle (DMSO) was washed in and work loops were repeated. Results: HCM slices performed more work at baseline compared to nonfailing slices. Across groups, slices demonstrated an increase in total work in response to isoproterenol (known positive inotrope) and a decrease in total work in response to mavacamten (known negative inotrope). Sotagliflozin significantly reduced total work done by slices at a given load. Conclusions: We developed a rigorous and reproducible methodology for phenotyping contractile behavior, including biomimetic work loops, in freshly prepared human LMS at multiple preloads and afterloads. SGLTi acutely and directly reduced the total work performed in human myocardial tissue. Future work is focused on the mechanisms by which SGLTi directly impact contractility.
Abstract 4144219: Safety and Efficacy of Rechallenging Immune Checkpoint Inhibitors After Discontinuation Due to Immune-Associated Myocarditis in Cancer Patients
Authors: Jian Zhang, Mengxiao Han, Zheng Li, Yan Wang, Leilei Cheng
Journal: Circulation (2024)

Background: Immune checkpoint inhibitor-associated myocarditis (ICIAM), a highly fatal immune-related adverse event (irAE) in cancer patients receiving immune checkpoint blockade (ICB) therapy, necessitates immediate termination of ICB once diagnosed. Research Questions: However, no studies have yet explored how to safely and effectively rechallenge ICB for long-term tumor control. Aims: To investigate the clinical course, treatment, and prognosis of patients with ICIAM undergoing ICB rechallenge (ICBR). Methods: This study retrospectively evaluated consecutive patients admitted to Zhongshan Hospital with clinically diagnosed ICIAM according to the 2022 European Society of Cardiology (ESC) guidelines from January 2020 to April 2022. Clinical, biological, imaging, treatment, and prognostic data were collected. Patients were grouped based on the recurrence of irAE following ICBR. Results: A total of 23 ICIAM patients (64.39 ± 9.40 years) who underwent ICBR were included. According to the Common Terminology Criteria for Adverse Events (CTCAE), myocarditis grades were: 11 patients (47.83%) with grade 1, 5 patients (21.74%) with grade 2, and 7 patients (30.43%) with grade 3. The median initial cardiac troponin T (cTnT) was 0.072 ng/ml (IQR, 0.037-0.096). Fourteen patients (60.87%) were administered glucocorticosteroids (GC). Twelve patients (52.17%) reported a recurrence of irAE following ICBR, including elevated cTnT (58.33%), pneumonia (16.67%), enteritis (8.33%), thyroiditis (8.33%), hypocortisolism (8.33%), and hemophagocytic syndrome (8.33%). A higher proportion of patients who developed irAEs following ICBR were administered GC (75% vs. 45.45%, p&lt;0.001). The median progression-free survival (mPFS) was 8.5 months (95% CI: 6, NA) after ICBR. Conclusions: Rechallenging immunotherapy for patients with ICIAM was relatively safe and controllable, despite the potential recurrence of non-fatal irAEs. Additionally, patients often achieved better tumor control after ICBR, indicating that ICBR can be a viable option for maintaining long-term tumor management.
Abstract 4144167: Efficacy of Stem Cell Transplantation in Cardiac Regeneration and Function in Ischemic Heart Disease: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Ravipati Shivani, Osama Ahmad, Vibha Sri Nandipi, Bejoi Mathew, ANITA MICHAEL, Vindhya Vasini, Sumitaksha Banerjee, Sakoon Kaur, konakanchi Bhargav pradeep, Rishabh Baskara Salian, Tarun Kumar Suvvari
Journal: Circulation (2024)

Background: Myocardial ischemia remains a significant global health concern for cardiovascular morbidity and mortality. In addition to the traditional treatment modalities, stem cell transplantation is emerging as a promising therapeutic intervention for cardiac regeneration and functional recovery. Our study evaluated the efficacy and clinical impact of SCT by reducing infarct scar size and improving cardiac function. The secondary objectives are to compare stem cell types, identify optimal transplantation strategies, and address safety and feasibility. Method: Randomized controlled trials from January 2000 to July 2023 were collected from PubMed, Cochrane, Google Scholar, and Elsevier. Based on criteria and evidence quality, screening and selection were done. A RevMan analysis was done. Infarct size, LVEF, LVESV, LVEDV, and mortality were measured. Comparator variables included placebo, medical therapy, CABG, and other types of stem cells. Randomization, allocation concealment, blinding, and therapeutic interventions differed among trials. Heterogeneity and publication bias were assessed using random-effects model and funnel plots. Sensitivity analysis and meta-regression identified outcome variability. Results: Seventeen studies (n = 1022 patients) met the inclusion criteria, encompassing various cell types, doses, and administration routes. Compared to controls, SCT greatly enhanced LVEF (MD: 3.39, 95% CI: 1.05 to 5.73, p = 0.005) and reduced infarct size (MD: 14.23, 95% CI: 7.12 to 21.35, p&lt;0.0001) with an average dose of 2.03 x 107 cells/ml injected intracoronarily directly into the infarcted myocardium or the target vessel. LVESV (MD: -2.63, 95% CI: -7.99 to 2.73, p = 0.34) or LVEDV (MD: -2.00, 95% CI: -4.40 to 0.40, p = 0.10) did not improve. Differences in mortality rates were insignificant (OR: 0.71, 95% CI: 0.29 to 1.74, p = 0.46). A diverse range of patients was included, leading to moderate heterogeneity (I^2 = 52%). Conclusion: SCT shows potential benefits for cardiac regeneration and functional improvement. The analysis is robust, with no publication bias and mild attrition bias issues. Due to low mortality, safety was comparable to conventional therapy. These findings highlight the need for SCT strategy optimization and long-term clinical outcome studies.
Abstract 4144254: Sex Differences in the Association of Leisure Time Physical Activity and Incident Peripheral Artery Disease
Authors: Maria Pabon, Alberto Foa', Brian Claggett, Kelly Evenson, Kuni Matsushita, Scott Solomon, Sheila Hegde
Journal: Circulation (2024)

Background: The benefit of leisure time physical activity (LTPA) in preventing peripheral artery disease (PAD) is well established. However, no prior studies have examined how longitudinal changes in LTPA during mid-life influence the risk of future PAD in men and women. Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study who attended visit 3 and were free of PAD [ankle brachial index (ABI) &gt;0.90] with available ABI during follow-up (measured ~5, 18, and 25 years after visit 3). LTPA was assessed using the modified Baecke questionnaire and defined as ideal, intermediate, or poor by the American Heart Association. Change in LTPA from visit 1 (1987-1989) to 3 (1993-1995) was subcategorized as 1) persistently poor, 2) decreased, 3) increased, or 4) persistently active. The primary outcome of time-to-incident PAD after visit 3 (ABI ≤ 0.90), was assessed using Cox models adjusted for relevant covariates. Results: A total of 8,421 participants were included (mean age 59 ± 5.5 years, 56% women, 20% Black). From visit 1 to 3, 1,609 participants had persistently poor LTPA, 1,860 decreased their activity, 2,015 increased their activity, and 2,937 remained persistently active. During a median follow-up of 17.7 years, 853 ARIC participants developed PAD (471 women and 382 men). An increasing or persistently active level of LTPA was associated with lower risk of incident PAD (HR 0.74 (0.60, 0.89) p=0.003 and HR 0.71 (0.58, 0.85) p&lt;0.001 respectively) compared to persistently poor LTPA. There was no difference between those in the decreasing LTPA category and those with persistently poor LTPA (HR 0.88 (0.72, 1.09) p=0.24). There were no interactions with race, age, or body mass index; however, there was significant effect modification by sex (p-int 0.01). Men who increased activity or were persistently active had lower risk of developing PAD as compared to those with persistently poor LTPA ( Table ). There was no association between changes in LTPA and incident PAD in women. Conclusions: Maintaining or increasing LTPA over six years was associated with decreased risk of incident PAD in men but not in women. Further research is needed to clarify sex differences in these associations.
Abstract 4144216: Have Gender-Specific Outcomes After STEMI Improved? – A Meta-Analysis of the Past Decade
Authors: Jesslyn Hariyanto, Catherine Jillian Hardi, Jessica Anastasia Setiawan, Sunanto Ng
Journal: Circulation (2024)

Background: Over the past decade, research has focused on gender disparities in cardiovascular outcomes. Historically, women have had higher mortality rates and worse outcomes after STEMI compared to men. This study aims to investigate if advancements in interventional cardiology and pre-hospital and in-hospital care have improved outcomes for women over 10 years. Methods: PubMed, Scopus and Cochrane were reviewed for cohort studies and registries from 2014-2024 comparing male and female STEMI patients, focusing on mortality, reinfarction, heart failure, stroke, and stent thrombosis. In-hospital and 1-year outcomes were assessed. Statistical analysis used Review Manager and I^2 for heterogeneity with a random-effects model. Results: We found 28 studies from 39 countries, with 39% female participants. T2DM was prevalent for 33.2% of males and 36.9% of females, with 32.2% of males and 21.3% of females being smokers. Both genders had an equal history (50%) of previous MI, PCI, and CABG. Primary PCI was performed in a majority (73%) of male patients compared to 62% of female patients; while thrombolysis was received by 73.1% of males and 61.5% of females. For in-hospital outcomes, women have a higher all-cause mortality risk (RR = 1.77, 95% CI: 1.65-1.91), consistent in 2014-2018 (RR = 1.75, 95% CI: 1.49-2.05) and 2019-2024 (RR = 1.79, 95% CI: 1.63-1.96; P = 0.81) Women have higher risks of stroke (RR = 1.64, 95% CI: 1.34-2.02) and heart failure (RR = 1.50, 95% CI: 1.31-1.70) No significant differences were found in reinfarction (RR = 1.19, 95% CI: 0.82-1.74) or stent thrombosis (RR = 1.05, 95% CI: 0.53-2.07) At 1 year, women have a significantly higher all-cause mortality risk (RR = 1.94, 95% CI: 1.48-2.53), observed in both 2014-2018 (RR = 1.77, 95% CI: 1.26-2.50) and 2019-2024 (RR = 1.98, 95% CI: 1.45-2.72; P = 0.64) Women also face higher cardiovascular mortality (RR = 2.45, 95% CI: 1.11-5.40) and stroke risk, (RR = 1.85, 95% CI: 1.43-2.39) with no significant difference in reinfarction risk (RR = 0.96, 95% CI: 0.53-1.73) Conclusion: Women with STEMI still face higher risks of in-hospital and 1-year all-cause mortality, stroke, and heart failure compared to men, indicating insufficient improvement in outcomes. There were no significant differences in reinfarction and stent thrombosis. It is important for future efforts to focus on understanding these disparities to improve outcomes for women.
Abstract 4144133: Racial And Ethnic Disparities In Outcomes Of St Segment Elevated Myocardial Infarction With Percutaneous Coronary Intervention
Authors: Godbless Ajenaghughrure, Kenan Rahima, Kamal Shemisa, AAVASH MISHRA, Gehna Kishore, Nadim Jaafar
Journal: Circulation (2024)

Background: Racial disparities in healthcare are a persistent and troubling issue, with profound implications for patient outcomes and societal well-being. Despite advances in medical science, studies consistently show that minority patients, particularly African Americans and Hispanics, face higher rates of STEMI incidence, delayed treatment, and poorer outcomes compared to their white counterparts. Methods: we examined the national inpatient sample 2017-2020 for adult admitted with st segment myocardial infarction,we compared the clincal outcome of patients admitted with stemi with pci based on racial distribution.STATA 18th edition was used for analyses. Age, gender, race, hypertension, diabetes, obesity, dyslipidemia, and Elixhauser comorbidity index were identified as confounders by univariate analyses and tested further with multivariate logistic regression models. The primary outcome was mortality. Secondary outcomes were the need for intubation, cardiac arrest, length of stay (LOS), and total hospital charges. Results: There were 582420 hospitalizations with STEMI with PCI. Mean age was 62 yrs and 71% were male. Among the admitted patients, Caucasians were 425064 (66.1%), Blacks were 47635(8.2%),Hispanics were 47555(8.2%), Asians were 16004(2.8%). . All-cause mortality in patients admitted with STEMI with PCI were 34090 where subgroup Analysis with Caucasians, Blacks ,Hispanics and Asians had 23700 (5.6%) vs 32870 (6%) vs 2915(6.1%) and 1155(7.2%) respectively. Further subgroups analysis revealed that Asians (10.8%, aOR 1.77 CI 1.54-2.03,P value&lt;0.001) were more likely to require intubation,followed by Hispanics(10.1% aOR 1.46 CI 1.33-1.6, p value &lt;0.001) ,then Blacks (9.4% aOR 1.2,CI 1.09-1.32 P vale &lt;0.001)and caucasians were least likely to require intubation(7.6% ) Finally, racial subgroup showed significant primary andsecondary outcomes that are presented in Table 1. Conclusion: All obtained results revealed statistical significance and we considered Caucasian population as baseline. Mortality, intensive care services and resource utilization proportion was highest among Asian race followed by Hispanic race then by Black race. Understanding these disparities is essential for improving healthcare equity and ensuring that all patients receive appropriate and equitable care regardless of their racial or ethnic background.
Abstract 4144240: Weight gain and the risk of sudden cardiac death in coronary artery disease
Authors: Maria Hannula, Lauri Holmstrom, Mikko Tulppo, Ida Hookana, Juha Perkiomaki, Heikki Huikuri, Juhani Junttila
Journal: Circulation (2024)

Background: Obesity increases the risk of sudden cardiac death (SCD) in the general population, but in patients with CAD, obesity has been associated with a smaller risk of death. This ‘obesity paradox’ is confounded by several factors and the association between weight gain and the risk of SCD in CAD is unclear. Aim: We aimed to investigate the effect of weight gain on the risk of SCD in a prospective cohort of CAD patients. Methods: We have prospectively enrolled 1,946 patients with CAD (mean age 66.9±8.6, 68% male), with a mean follow-up of 8.7±2.2years. Weight was measured at baseline and at 5 years and was classified into 3 groups: 1) -5%&lt; weight change &lt;+5% (reference group), 2) weight gain &gt;5%, and 3) weight loss &gt;5%. The primary endpoint was SCD or resuscitation from sudden cardiac arrest. Non-sudden cardiac death and non-cardiac death were secondary endpoints. Statistical analysis was performed with Cox regression and was adjusted for age, sex, baseline BMI, type 2 diabetes, kidney function (eGFR), and left ventricle ejection fraction. Results: A total of 1,053 subjects had weight measured at baseline and at 5 years. Thirteen percent (13%) gained weight &gt;5% and 19% lost weight &gt;5% in 5 years. During a mean follow-up of 2.1±0.7 years after the second weight measurement, SCDs/SCAs occurred in 18 patients. Weight gain was associated with an increased risk of SCD (HR 3.54, 95% CI 1.17-10.67; p=0.03), but not with non-cardiac death (HR 2.01, 95% CI 0.97-4.19; p=0.06) or non-sudden cardiac death (no events). Weight loss was associated with an increased risk of non-sudden cardiac death (HR 2.74, 95% CI 1.07-6.97; p=0.04) and non-cardiac death (HR 2.60, 95% CI 1.40-4.81; p=0.002) but not with SCD (HR 1.73, 95% CI 0.51-5.86; p=0.38). Conclusions: Weight gain was associated with an increased risk of SCD but not with other modes of death. Patients with stable weight had the best prognosis. These results suggest that weight changes may have a special effect on CAD trajectory and further studies are warranted to investigate the role of weight gain on SCD risk.
Abstract 4144077: Sudden death in hypertrophic cardiomyopathy – what is the role of coronary artery disease?
Authors: Harpriya Chugh, Audrey Uy-Evanado, Kotoka Nakamura, Kyndaron Reinier, Sumeet Chugh
Journal: Circulation (2024)

Background: Myocardial ischemia is a potential trigger for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) but significant coronary artery disease (CAD) is not considered in clinical risk stratification calculators. The overlap between HCM and CAD needs further investigation, especially in the general population. Hypothesis: A large proportion of patients with HCM who suffer SCD, have associated significant CAD. Methods: From an ongoing prospective, population-based study of SCD in the Northwestern US (catchment pop. ≈1 M, 2002-2020), we performed a case-case analysis. Comparisons of the lifetime clinical history and available autopsy findings were made between SCD cases with HCM and CAD(HCM-CAD) vs. HCM without CAD(HCM-NCAD). HCM was defined as left ventricle (LV) wall thickness ≥15mm in the absence of any other cause for LVH. Univariate and multivariate analyses were conducted. Results: A total of 5962 (male 67%, age 64±19yr, black 9%) SCD cases with detailed clinical data were evaluated and 2.9% (n=177, male 84%, age 46±16yr, black 12%) met criteria for HCM. HCM-CAD was observed in 86 (48.6%). When compared to HCM-NCAD (n=91), HCM-CAD were more likely to be male (93% vs 75.8%, p =0.002) and older (51±15 vs 41±16 years, p&lt;0.0001) (Figure). The multivariable model showed that HCM-CAD were older (OR :1.1 [1.0-1.1]) and male (OR 5.9 [2.0-18.0]). Heart failure (OR 0.18 [0.05-0.68]) and asthma (OR 0.19 [0.05-0.71]) were more common in HCM-NCAD. Out of those with symptom data available (n=152), chest pain as a warning symptom was more common in HCM-CAD vs HCM-NCAD (20.8% vs 8%, p =0.03). Conclusion: Approximately 50% of HCM who suffered SCD had associated significant CAD, suggesting that myocardial ischemia could be an important trigger of SCD in HCM. These findings highlight the importance of CAD as a risk modifier for SCD in HCM and should be investigated further.
Abstract 4144145: Mavacamten-induced Augmentation of Exercise Strain is the Mechanical Basis for Improvement in Exercise Capacity in Obstructive Hypertrophic Cardiomyopathy
Authors: Morgane Herry, Chun-Tai Mao, Maria Roselle Abraham, Theodore Abraham
Journal: Circulation (2024)

Background : Mavacamten reduces left ventricular outflow tract gradients (LVOTg), improves symptoms and increases exercise capacity in symptomatic obstructive hypertrophic cardiomyopathy (oHCM) patients. We investigated the potential myocardial mechanical basis for improved exercise capacity in these patients. Methods: We evaluated symptoms, exercise capacity in metabolic equivalents (METs), LVOTg at rest, at Valsalva and peak-exercise, and global left ventricular longitudinal strain (GLS) at rest and peak-exercise in patients before and during mavacamten therapy. Results: oHCM patients at a single tertiary center (n=22, 56% female, mean age 64 ± 12 years) were evaluated pre- and post-mavacamten initiation (Table). Mean duration of treatment was 22 ± 14 weeks. There was significant improvement in NYHA class – proportion of NYHA I increased from 0 to 64% and NYHA II and III decreased from 77 to 34% and 23 to 5%, respectively (Figure B). All patients underwent a symptom-limited Bruce protocol treadmill stress echocardiogram and there was a significant improvement in exercise capacity pre- vs. on-mavacamten (7.6± 3.4 vs. 8.6± 3.4 METs, respectively, p 0.01). There was a significant decrease in LVOTg at rest, at Valsalva and post-exercise (47 ± 43 vs. 9.8 ±6 mmHg, 82 ± 46 vs 20 ± 19 and 114 ± 54 vs. 43 ± 40 mmHg, respectively, all p &lt; 0.001). Rest GLS did not change pre- vs. on-Mavacamten (15 ± 3 vs. 16 ± 3%, p 0.07). However, peak-exercise GLS improved significantly (16 ± 4 vs. 18 ± 4%, pre vs. on-mavacamten, p &lt; 0.01) (Figure A). Conclusion: Mavacamten-induced augmentation of exercise strain may be the mechanical basis for exercise capacity improvements in oHCM. Rest GLS non-significantly increased on mavacamten. Our results will need validation in a larger cohort.