tbuckley/cabot-search huggingface dataset:
Abstract 18375: Improving Rate of Prenatal Diagnosis of Critical Congenital Heart Disease Despite the Covid19 Pandemic: A Canadian Multiprovincial Study
Authors: Luke G Eckersley, Jane Lougheed, Deborah S Fruitman, Adrienn B.Szabo, Mrinal M Lad, Heili Poolsaar, Rose He, Lynne E Nield, Varsha Thakur, Lisa K Hornberger, Bhawna Arya, Lindsay R Freud
Journal: Circulation (2023)

Background Restriction to travel, reallocation of health resources and physical distancing during the COVID19 pandemic caused extraordinary health system strain, requiring limited tertiary referral acceptance. The overall impact of public health measures during COVID19 on diagnosis of congenital heart disease (CHD) has not been explored. We sought to determine the rate, timing of diagnosis and pregnancy outcomes of critical CHD prior to and during the COVID era. Methods: Cases of CHD with due date/birth date from 1 Jan 2016 to 1 Mar 2022 that required or were anticipated to require neonatal intervention were identified from surgical and referring centres in Ontario and Alberta. Pregnancies were categorized as reaching 18 weeks GA before (pre-COVID) or after 1 March 2020 (COVID). Outcomes included timing of diagnosis (pre/postnatal), GA at prenatal diagnosis, and pregnancy outcome. Data are presented as mean, 95% CI or median (IQR); rank-sum comparison of continuous variables or Chi 2 comparison of proportions were used. Results: Prenatal diagnosis occurred in 1240/1823 (68% (65.8, 70.1)) of cases of critical CHD overall, with a pre-COVID rate of 867/1305 - 66% (64, 69) and COVID rate of 373/518 - 72% (68, 76), p=0.02. During COVID, earlier median GA at obstetric ultrasound (median GA: pre-COVID 20.1 (19.1, 22), COVID 19.9 (19.1,21.3), p=0.025) and diagnosis of CHD (median GA: pre-COVID 21.7 (20.3, 24.3), COVID 21.3 (20,23.3), p=0.006) occurred. Prenatal diagnosis before 22 weeks GA (pre-COVID 449/851, 52.3% vs COVID 219/371, 59%; p=0.043) and termination were more common during COVID (pre-COVID 28% (25,31), COVID 35% (30,40) p=0.015). Conclusion The rate of prenatal diagnosis of critical CHD continued to improve during the COVID pandemic in two of Canada’s largest provinces. Unexpectedly, obstetric ultrasounds occurred earlier, leading to earlier prenatal diagnosis of CHD. These findings may have implications for referral practices in the post-COVID era.
Abstract 15064: Programmed Death-Ligand 1 Attenuates Myocardial Injury Following Myocardial Infarction
Authors: Yuanjia Zhu, Sabrina K Walsh, Akshay Venkatesh, Seung Hyun Lee, Danielle Mullis, Charles J Stark, Nicholas Tran, Sidarth Ethiraj, Luca E Lin, Catherine A Wu, Amanda S Padilla Lopez, Basil M Baccouche, Umayr Syed, Long T Doan, Shin Yajima, Stefan Elde, Hanjay Wang, Matthew H Park, Christopher Jackson, Michael Lim, Y Joe Woo
Journal: Circulation (2023)

Introduction: Myocardial infarction (MI) represents a major global cause of morbidity and mortality. Immune therapy to mitigate the secondary injury to myocardial tissues following MI is lacking. Programmed death-1 (PD-1) is an inhibitory protein expressed by immune cells during activation. Programmed death-ligand 1 (PDL1) binds to PD-1 and limits collateral damage in diseases with chronic inflammatory response. The objective of this study was to evaluate the impact of PDL1 on myocardial injury following MI. Methods: 56 C57BL/6 male and female mice underwent left anterior descending artery (LAD) ligation. Mice were randomized to receive 50 μg of PDL1 (14 intramyocardial, 14 intraperitoneal) or PBS (12 intramyocardial, 16 intraperitoneal) immediately after LAD ligation. Echocardiography was obtained at baseline and 2 weeks after MI. Mice hearts were then explanted and sectioned for Masson’s trichrome staining. An additional 25 mice after MI without treatment were terminated on postoperative day 1, 3, 5, 7, and 14. Peripheral blood and myocardium were stained for CD45, CD11b, Ly6c, and PD-1 for flow cytometry. Results: Myocardial infarct size reduction was observed after PDL1 treatment ( Fig. A-C ). Compared with controls, PDL1 delivered intramyocardially significantly improved ejection fraction from 29.8 ± 12.4 % to 41.4 ± 14.0 % (p = 0.04), and when delivered intraperitoneally, from 32.5 ± 9.4 % to 47.7 ± 8.0 % (p &lt; 0.0001, Fig. D ). In the myocardium, the percentage of monocytes that were PD-1+ surged from 0.2 ± 0.2 % on day 1 to 83.8 ± 17.7 % on day 3 and remained elevated 14 days after MI at 31.5 ± 23.6 % ( Fig. E ). Conclusions: PDL1 can attenuate myocardial injury and partially preserve cardiac function following MI in a rodent model. PD-1+ monocytes may be one of the key mediators of secondary myocardial injury after MI. Future studies will determine the mechanism of how PDL1 salvage myocardial damage to help develop a potential novel therapy.
Abstract 16672: Effects of Evinacumab on Atherogenic Lipoproteins in Children and Adolescents From Ages 5 to 17 Years With Homozygous Familial Hypercholesterolemia
Authors: Eliot A Brinton, Daniel Gaudet, Frederick J Raal, Albert Wiegman, Carissa M Baker-Smith, Patrick M Moriarty, Susanne Greber-Platzer, Robert S Rosenson, Alpana Waldron, shazia ali, Paul Skiba, Richard T George, Robert Pordy, Xue-Qiao Zhao
Journal: Circulation (2023)

Background: Homozygous familial hypercholesterolemia (HoFH) is characterized by severely elevated LDL-C levels from birth. Diagnosis and aggressive LDL-lowering treatment (LLT) before adulthood are essential for optimal ASCVD prevention in HoFH; however, it is often undiagnosed and undertreated in pediatric patients. Specifically, HoFH children and adolescents routinely require advanced LLT, since few achieve LDL-C goal on standard LLT. Evinacumab, a novel angiopoietin-like-3 inhibitor and advanced LLT, has an established safety profile in younger and older pediatric HoFH patients, 5-11 and 12-17 years, respectively. For the first time, we compare its lipid efficacy in these two groups. Methods: Fourteen patients ages 5-11 years (Study 17100 part B; NCT04233918) and 14 patients ages 12-17 years (Study 1719; NCT03409744), all with HoFH on stable LLT, were treated with IV evinacumab 15 mg/kg Q4W. Notably, in Study 17100 part B, no patients were taking PCSK9 inhibitors at study entry, while in Study 1719, 42.9% of patients were receiving a PCSK9 inhibitor at baseline. Apheresis use differed little, 50.0% in the younger study vs 64.3% in the older. LDL-C and other atherogenic lipoproteins were tested at baseline and 24 weeks. Results: In patients ages 5-11 years, mean (SD) baseline LDL-C was 263.7 (91.0) mg/dL and was lowered 48.3% (131.9 mg/dL) by evinacumab ( Table ). In patients ages 12-17 years, baseline LDL-C was 300.4 (100.5) mg/dL and was lowered 55.4% (180.5 mg/dL), with similar baseline and changes to those of the younger patients. In both groups, evinacumab markedly reduced ApoB, non-HDL-C, and Lp(a) ( Table ). Conclusions: Evinacumab strikingly and comparably reduces atherogenic lipids in younger and older pediatric HoFH patients. Since standard LLT rarely lowers LDL-C levels to treatment goals in pediatric HoFH, evinacumab should be strongly and urgently considered in these patients whenever further LDL-lowering is needed after optimizing standard LLT.
Abstract 18357: Racial Disparities in Direct Oral Anticoagulant Orders in Patients With Nonvalvular Atrial Fibrillation Within A Large Integrated Health System
Authors: Victor S Escobedo, Daniela Wong Pacheco, Mengnan Zhou, Mingsum Lee, Daniel T Lang, Jaejin An
Journal: Circulation (2023)

Introduction: Anticoagulant (OAC) use for stroke prevention in non-valvular atrial fibrillation (NVAF), specifically direct oral anticoagulants (DOAC) use, is suboptimal in racial/ethnic (RE) minorities. Hypothesis: We hypothesized differences in OAC and DOAC orders among RE groups over time in patients newly diagnosed with NVAF from 2012-2022 within a large US integrated healthcare system. Methods: We conducted a retrospective cohort study using Kaiser Permanente Southern California electronic medical record data on adults with NVAF between 2012-2022. We compared the proportion of OAC and DOAC orders within 60 days from the first NVAF diagnosis among those with a CHA 2 DS 2 -VASc score ≥2 across self-reported RE groups over time using chi-squared tests. Multivariable logistic regression was used to compare OAC and DOAC orders in RE groups compared with non-Hispanic White (NHW) adjusting for age, sex, and CHA 2 DS 2 -VASc score. Results: Of 59,340 OAC eligible patients from 2012-2022, 52% of patients received an OAC order and 33% received a DOAC order. DOAC orders across all RE groups increased over time, with DOAC orders comprising 95% of all OAC orders for new NVAF patients in 2022. The percentages of OAC and DOAC orders were highest among NHW patients in most years. In 2022, OACs were ordered at higher rates for NHW (67.1%) than Asian (67.0%) (OR=0.84, 95% CI=0.67-1.05), Hispanic (65.6%) (OR=0.63, 95% CI=0.54-0.74), or non-Hispanic Black (62.0%) (OR=0.54, 95% CI=0.43-0.68) patients. In 2022, DOACs were ordered at higher rates for NHW (65.3%) than Asian (64.2%) (OR=0.78, 95% CI=0.63-0.98), Hispanic (64.1%) (OR=0.64, 95% CI=0.55-0.75), or non-Hispanic Black (60.7%) (OR=0.55, 95% CI=0.44-0.69) patients ( Figures 1a/1b ). Conclusions: Although DOAC orders have been increasing over time across all RE groups, minority groups were still less likely to receive OAC or DOAC orders than NHW patients.
Abstract 15300: Short-Term Outcomes in Different Revascularization for Acute Coronary Syndrome With Cardiogenic Shock Supported by Impella -Report From Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD Registry)
Authors: Masahiko Fujii, Tomoki Sakata, Shinichi Okino, Kenji Mogi, Manabu Sakurai, Yoshiharu Takahara, J-PVAD Investigator
Journal: Circulation (2023)

Introduction and Hypothesis: Percutaneous coronary intervention (PCI) has tended to be selected for the treatment of acute coronary syndrome with cardiogenic shock because of its ability of earlier and less-invasive therapy, though coronary artery bypass grafting (CABG) can perform complete revascularization. We hypothesized that Impella® support has the potential to make surgical treatment much safer because Impella® can improve hemodynamic state and could have the possibility to mitigate myocardial ischemia by unloading the left ventricle. Methods: The aim of study is to investigate if surgical revascularization is safe and effective treatment by comparing short-term outcome with different revascularization including PCI, CABG, and hybrid therapy (PCI followed by CABG). Of 1102 cardiogenic shock cases with Impella (994 cases in PCI, 48 cases in CABG, and 63 cases in Hybrid therapy) between February 2020 and December 2021 enrolled in the J-PVAD registry, short-term outcomes were compared between 62 propensity-matched cases between PCI (n=31) and CABG (n=31), as well as 68 matched cases between PCI (n=34) and hybrid therapy (n=34). Results: There was no difference in all-cause mortality between the PCI and CABG group as well as PCI and hybrid therapy group. The PCI group had a greater number of NYHA class≦2 at discharge than the CABG group (17 (54.8%) in the PCI group vs 10 (32.2%) in the CABG group, p=0.012). There was no difference in the number of NYHA class≦2 at discharge between the PCI and hybrid therapy group (18 (52.9%) in the PCI group vs 15 (44.1%) in the hybrid therapy group, p=0.12). Conclusions: CABG and hybrid therapy showed acceptable short-term outcome compared to PCI.
Abstract 15197: Differential Impact of Factor XII, Factor XI and Prekallikrein Deficiency on Thrombosis: A Pro-Thrombotic Vascular Action of Bradykinin
Authors: Lejia Hu, Pengfei Xu, Miao Wang
Journal: Circulation (2023)

Objective: Factor XII (FXII) initiates the plasma contact system that triggers the intrinsic coagulation pathway and the kallikrein-kinin pathway via factor XI (FXI) and plasma prekallikrein (PK), respectively. The importance of the contact system for thrombosis sparing hemostasis is well established, however a comprehensive head-to-head comparison of the three proteases in arterial thrombosis is missing. Approach and Results: We produced mice deficient in FXII ( F12 -/- ), FXI ( F11 -/- ) and PK ( Klkb1 -/- ) and compared them in two distinct thrombosis models. While all (100%) of WT mice formed occlusive thrombi upon 30% ferric chloride challenge, carotid artery occlusion was reduced to 0, 4.8, 27.3 % in F12 -/- , F11 -/- and Klkb1 -/- mice (n=14-22), respectively. Upon photochemical-induced cremaster arteriolar thrombosis, occlusion time (s) prolonged to 226.1±60.4, 123.8±32.0 and 87.8±25.3 (mean±SEM, n=10-15) respectively in F12 -/- , F11 -/- and Klkb1 -/- mice, largely exceeding WT levels (38.3±12.1). A discordance was observed between in vivo thrombotic effects of the proteases and their roles for ex vivo coagulation, which ranked FXII≈FXI&gt;PK as assayed by thromboelastography and activated partial thromboplastin time. Activation of FXII promoted thrombosis in WT and Klkb1 -/- mice, and impressively, it also accelerated thrombosis in F11 -/- mice, increasing activated PK activity and plasma bradykinin formation. Infusion of bradykinin and blockade of degradation of endogenous bradykinin increased platelet-endothelium adhesion and promoted thrombotic occlusions, which involved bradykinin mediated endothelial cell-release of platelet activating factor, rather than direct activation of platelets by bradykinin. Conclusion: FXII, FXI and PK differentially mediate experimental thrombosis in vivo and FXII/FXI appear as superior targets for thrombosis as compared to PK. PK- bradykinin axis activated by FXII contributes to thrombosis in vivo .
Abstract 16756: Trends of Cardiovascular Deaths in Patients With Melanoma From 2005 to 2019: An Analysis Based on SEER Program Database
Authors: Astha Prasai, Nischit Baral, Shailesh Niroula, Prakash Banjade, Kamal Kandel, Amrit Devkota, Ejaz ahmad A Khan, Mamata Bista, Joshua D Mitchell
Journal: Circulation (2023)

Introduction: Melanoma is the fifth most common cancer diagnosis in the United States. With recent advances in treatment modalities, including immune checkpoint inhibitors (ICIs), targeted therapies, there has been improvement in survival among melanoma patients. However, increasing resistance and treatment related adverse effects (TrAEs) are being reported including cardiovascular side effects. Objectives: To evaluate the trend of cardiovascular specific death rate among patients with melanoma. Methods: We used Surveillance, Epidemiology, and End Results (SEER) Program database 17 registries from 2000 to 2019 and SEER*Stat Version 8.4.1 software to analyze the data using the rate session. Joinpoint software, version 4.7.1.0 was used to create log-linear time trends annually. Results: Our study included 301,632 patients with melanoma from 2005 to 2019. The annual percentage change (APC) of melanoma was 0.46% (95% CI -1.45 to 1.07, p&gt;0.05) annually from 2005 to 2011 and 3.33% (95% CI 1.79 to 4.27, p&lt;0.05) annually from 2011 to 2014 and the incidence rate decreased by 0.06% (95% CI -1.44 to 0.5, p&gt;0.05) annually from 2014 to 2019. Melanoma specific mortality rate increased annually by 2.03 % (95% CI 0.78 to 3.94, P &lt;0.05) from 2005 to 2013 and decreased by 5.49% annually (95% CI -8.65 to -3.65, P &lt;0.05) from 2013 to 2019. Cardiovascular disease specific mortality rate increased by 7.08% annually (95% CI 4.66 to 9.64, P &lt;0.05) from 2005 to 2019. (Figure 1) Conclusion: Our study shows that there has been an annual increase in cardiovascular specific mortality rate from 2005 to 2019, while there was annual decrease in melanoma specific mortality rate from 2013 to 2019. Increase in cardiovascular specific death rates could be due to the direct toxicity of newer therapies and prolonged survival, which further could be due to advancement in diagnostics and newer therapies.
Abstract 15350: Differing Impacts of Cardiac Implantable Electronic Device Leads on Tricuspid Regurgitation
Authors: Sophie A Leon, Melissa A Austin, Chitra Parikh, Danial Ahmad, Vakhtang Tchantchaleishvili, Behzad B Pavri
Journal: Circulation (2023)

Introduction: Placement of cardiac implantable electronic devices (CIED) is thought to contribute to tricuspid regurgitation (TR). However, there are relatively few data comparing the impact of different CIED lead types on the incidence and progression of TR. Aims: This study sought to quantify the change in TR severity following implantation of CIEDs with different types of leads. Methods: Demographic, diagnostic, and outcome data were collected on patients from a single implanter of cardioverter defibrillators (ICD), right ventricle-paced pacemakers (RV-PM), or His bundle-paced pacemakers (His-PM) from 2016 to 2019. Patients with previous CIEDs undergoing upgrade procedures were excluded. Severity of TR was compared before and after CIED implantation using one-sided Wilcoxon-signed rank test. Results: A total of 97 patients receiving CIEDs were analyzed, including 23 with ICDs, 63 with RV-PMs, and 11 with His-PMs. Median patient age was 72 years [IQR: 63, 81], and 44% of patients were female. Echocardiograms were obtained a median of 20 days [4, 91] before CIED implantation and 31 months [18, 43] following implantation. Baseline TR grade was comparable between groups (p = 0.65). TR severity significantly worsened after ICD implantation (p = 0.035), RV-PM implantation trended toward worsening TR severity (p = 0.099), and no difference was noted after His-PM implantation (p = 0.68) (Figure). There was no significant change in RA pressure, RV size or function, or LVEF following CIED implantation. Conclusions: The effect of CIED leads on TR represents a spectrum related to the type of lead and whether the tricuspid valve is traversed. ICD leads, which are bulkiest and traverse the valve, significantly worsened TR. His-PM leads, which do not traverse the valve, have no apparent effect on TR. The impact of RV-PM leads on TR severity appears in-between ICD and His-PM leads - although the lead traverses the valve, it is lighter than ICD leads.
Abstract 18270: Interagency Registry for Mechanically Assisted Circulatory Support Profile is Associated With Outcomes in Patients With an Impella 5.5 Ventricular Assist Device
Authors: Jean-Luc A Maigrot, Randall C Starling, Edward G Soltesz, Nicholas G Smedira, Michael Tong, Shinya Unai, Pavan Bhat, David Moros, Eugene H Blackstone, Aaron J Weiss
Journal: Circulation (2023)

Introduction: The Impella 5.5 left ventricular assist device (LVAD) can provide temporary mechanical circulatory support (MCS) in select patients with advanced heart failure (HF). The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile provides a standardized grading system for advanced HF patients receiving MCS, ranging from most (1) to least severe (7). Hypothesis: The INTERMACS profile is associated with outcomes in patients supported with an Impella 5.5 LVAD. Methods: From 2019-2022, retrospective review of perioperative characteristics, INTERMACS profile and outcomes in patients supported with an Impella 5.5. Results: When stratified by INTERMACS profile, there were 63 patients (28%) in profile 1, 73 (32%) in profile 2, 20 (8.8%) in profile 3, 72 (32%) in profiles 4-7. Indication for Impella 5.5 implant was primarily cardiogenic shock due to chronic HF (81; 52%), acute MI (33; 21%) or postcardiotomy (22; 14%) in profiles 1-3 and Impella 5.5-assisted cardiac interventions (cardiac surgery, VT ablation, PCI) (68; 94%) in profile 4-7 (p&lt;0.01). Composite freedom from death, durable LVAD, or heart transplant occurred for 63 (41%) profile 1-3 and 66 (92%) profile 4-7 patients (p&lt;0.01). Conclusions: Patients with advanced INTERMACS profiles (1-3) primarily underwent Impella 5.5 implant for chronic HF, postcardiotomy, or acute MI cardiogenic shock, whereas patients in profiles 4-7 primarily underwent Impella 5.5-assisted cardiac interventions. Patients with advanced profiles were more often transitioned to durable LVAD or heart transplant, however, also had higher rates of mortality.
Abstract 16311: Differential Outcomes of Primary Percutaneous Coronary Intervention Compared to Medical Management Alone for Very Elderly Patients With ST-Elevation and Non-ST-Elevation Myocardial Infarctions - A Systematic Review and Meta-Analysis
Authors: Hafiz Muhammad Fazeel, Saad U Malik, Shaheryar Ranjha, Amman Yousaf, Hamza Yousaf, Essa Salah Ud Din
Journal: Circulation (2023)

Introduction: ST-segment elevation myocardial infarction (STEMI) and NSTEMI in elderly are therapeutic challenges as percutaneous coronary intervention (PCI) is often withheld owing to concern for side effects. It is also unsure if outcomes vary for these two syndromes. Hypothesis: PCI is better than conservative medical therapy (CMT) in very elderly patients (age &gt; 80 years) and if such results vary with presence of transmural infarction. Methods: PubMed, Embase, Cochrane database and clinicaltrials.gov were searched for relevant studies. The primary end point was mortality outcomes for both syndromes and secondary outcomes included short and long term major adverse cardiovascular events (MACE) and bleeding events for NSTEMI patients. Results: Nine STEMI studies with N= 1528 (PCI= 1119, CMT= 409) and eleven NSTEMI studies with N= 36089 (PCI= 9770 , CMT= 26319) were included. For STEMI patients, PCI showed significantly better 30-day [RR= 0.35 (0.22-0.56), p= 0.01, I 2 =60.08], one-year [RR= 0.28 (0.17-0.47), p= 0.001, I 2 = 68.36] and long-term mortality [RR= 0.40 (0.12- 1.36), p= 0.001, I 2 =86.07]. These outcomes did not replicate in NSTEMI patients for whom no difference was found for in-hospital mortality [RR= 0.44 (0.17- 1.16), p= 0.08, I 2 = 59.9] and 30-days all-cause mortality [RR= 0.32 (0.29- 0.36), p=0.53, I 2 = 0.0]. However, 12-month outcomes were better with PCI for all-cause mortality [RR= 0.29 (0.23- 0.37), p&lt; 0.001, I 2 = 81.32] and MACE [RR= 0.44 (0.21-0.87), p=0.001, I 2 = 84]. The short-term bleeding risk seemed lower with CMT [RR=1.29 (0.56-3.09), p&lt; 0.001, I 2 =90.4] without any long-term bleeding difference [RR= 1.85 (0.21-16.24), p &lt; 0.001, I 2 = 99.2] though large heterogeneity and wide confidence intervals limit definite conclusions. Conclusions: PCI has significant mortality benefits especially for STEMI patients. For NSTEMI patients undergoing PCI, the extended mortality risk improves without concurrent increment in major bleeding risk.