tbuckley/cabot-search huggingface dataset:
Abstract 18998: Deletion of the Duffy Antigen Receptor for Chemokines Impairs Blood Flow Recovery in the Mouse Hindlimb Ischemia Model: Role of CCL11
Authors: Ghaith Aboud, Ragheb Harb, David Kim, Brandee Goo, Mourad OGBI, Praneet Veerapaneni, Ronnie Chouhaita, Philip Coffey, Richard Lee, Yali Hou, Avirup Guha, Hong Shi, Masuko Ushio-Fukai, Brian H Annex, Ha Won Kim, Neal L Weintraub
Journal: Circulation (2023)

Introduction: Peripheral Artery Disease (PAD) is characterized by obstruction of the arteries in the lower extremities. Impaired angiogenesis plays a major role in the progression of PAD. Pro-angiogenic and anti-angiogenic chemokines are modulated by binding to the Duffy antigen receptor for chemokines (DARC), a non-signaling receptor expressed primarily on erythrocytes. Incidence and severity of PAD is greater in Blacks, ~70% of whom do not express DARC on their erythrocytes due to a common gene variant. Here, we tested the hypothesis that hematopoietic-specific deletion of DARC impairs blood flow recovery in mouse hindlimb ischemia model. Methods: Twelve week old female DARC Flox/Vav1-Cre+ (DARC HKO ) and littermate Vav1-Cre- (wild type, WT) mice underwent unilateral femoral artery ligation and excision. Ischemic muscle tissue and plasma were analyzed at early ischemic phase (day three post ligation) and late ischemic phase (day fourteen post ligation). Blood flow recovery was measured weekly via laser Doppler imaging. Results: DARC HKO mice had poor blood flow recovery compared to WT mice (p&lt;0.05), along with reduced capillary formation and increased inflammation, necrosis and fibrosis in the ischemic gastrocnemius muscles. Amongst the various DARC-bound chemokines assayed, levels of CCL11 (a pro-angiogenic strong DARC-bound chemokine) were significantly reduced in the plasma of DARC HKO mice, both at early and late ischemic phases (p&lt;0.01). CCL11 levels strongly correlated with capillary formation in ischemic hindlimb. CCL11 levels in ischemic muscle tissue were significantly reduced in the DARC HKO mice in the early, but not late, ischemic phase. Conclusions: Loss of DARC on hematopoietic cells has a negative impact on the recovery of perfusion and angiogenesis in the murine hindlimb ischemia model, possibly due to reduced levels of CCL11 consequent to DARC deletion. These findings may be relevant to ethnic differences in susceptibility to PAD and suggest that therapies directed towards increasing CCL11 may be beneficial in Blacks with PAD.
Abstract 13090: Clinical Burden of Transthyretin Amyloid Cardiomyopathy (ATTR-CM) in the USA From 2004 to 2022
Authors: Kevin M Alexander, Anne S Ersboell, Christiane L Haase, Julie T Mortensen, mathew S Maurer
Journal: Circulation (2023)

Introduction: Advances in diagnosis and disease awareness have led to increased prevalence and incidence of diagnosed transthyretin amyloid cardiomyopathy (ATTR-CM) worldwide. At the same time, patients are being diagnosed at an older age and with multiple comorbidities. Current data on the clinical burden of ATTR-CM in the USA are lacking. Aims: To assess the clinical burden of ATTR-CM in terms of comorbidities, medication use, and healthcare resource utilization in a large US population over time. Methods: Data from 2004–2022 were extracted from TriNetX, a US database of electronic medical records covering in- and outpatient data. An algorithm using ICD-9/10 codes and RxNorm codes for clinical drugs (amyloidosis + cardiac manifestation – light chain amyloidosis) was used to identify patients with ATTR-CM. Included were adults ≥ 18 years old at index date (first ATTR-CM diagnosis per the algorithm) with ≥ 1 year of database history. Demographic characteristics at index, medication use and clinical encounters in the year pre-index, and comorbidities at any time pre-index were assessed in cross-sectional cohorts over time. Results: Of more than 78 million patients in the database, 12 209 fulfilled all inclusion criteria (2004–2008, n = 332; 2009–2013, n = 913; 2014–2018, n = 3392; 2019–2022, n = 7572). The prevalence of both ATTR-CM-related comorbidities and other comorbidities, as well as associated medication use, generally increased over time ( Table ). In the year before ATTR-CM diagnosis, a considerable proportion of patients had outpatient, inpatient and emergency visits; among patients with one or more clinical encounter, the median number of encounters (any encounter) was ≥ 10 across all cohorts ( Table ). Conclusion: In patients with ATTR-CM in this large US population, the clinical burden has become more complex over time, with an increasing proportion of patients having multiple morbidities and clinical encounters in the time before diagnosis.
Abstract 17557: Single Limb-Lead Electrocardiogram Accuracy in Screening for Ventricular Pre-Excitation
Authors: Sinan S Sayood, Denice Hodgson-zingman, Kevin F Kwaku
Journal: Circulation (2023)

Introduction: Consumer devices capable of recording bipolar ECGs have been investigated and validated for atrial fibrillation detection and QT interval monitoring. Application of the technology to other electrical abnormalities like Wolff-Parkinson-White (WPW) is limited but could enhance the ability to screen for risk of cardiac arrhythmias before they occur. Aims: 1. Determine how frontal lead ECGs perform in identification of ventricular pre-excitation (VPE).2. Determine which of the standard 3 bipolar leads perform best for this detection.3. Quantify the impact of training of the interpreter on identification of VPE with single lead tracings. Methods: Standard 12-lead ECGs were obtained from 20 patients before and after successful radiofrequency ablation of a single manifest accessory pathway. 3-second tracings were abstracted from leads I, II, and III from each ECG and were presented in random order to interpreters of varying experience and specialization who were asked to evaluate whether the tracing showed VPE. Results were tabulated to determine the accuracy of VPE identification. Descriptive statistics of the performance of each lead (alone and in combinations) and interpreter type were calculated. Results: A total of 52 respondents interpreted 5108 ECG tracings. Some respondents did not read all tracings and there were unequal numbers of respondents in the different interpreter categories. The Table below depicts the performance of each lead and respondent subgroups. Conclusions: VPE can be identified with reasonable accuracy using a single limb-lead ECG tracing, with lead I performing better than leads II and III. Addition of lead II or III improved accuracy by 5% only. Most consumer devices record lead I, suggesting that they could be used to screen for WPW. Interpreter specialization correlated more with accuracy than training status.
Abstract 15019: Graded Relationships Between Blood Pressure Levels and Cardiovascular Mortality in Patients With Type 2 Diabetes: Results From a Large Registry Cohort in Asia
Authors: Loraine Seng, Troy Puar, Yong Mong Bee, Tazeen H Jafar
Journal: Circulation (2023)

Introduction: Elevated BP is associated with increased risk of cardiovascular mortality. However, there is ongoing debate whether intensive BP lowering may paradoxically increase the risk of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM). This study was undertaken to understand the association of BP with risk of CVD mortality in patients with T2DM. Method: This was a cohort study on 83,721 patients with T2DM age 40 years or older using data from a multi-institutional diabetes registry in Singapore from 2013 to 2019. The relationships between BP and CVD mortality were analyzed using Cox multivariable regression model, adjusting for covariates including gender, use of anti-hypertensive medications and presence of co-existing CVD. Results: Overall, the mean age was 65.3 years with 50.6% women, 78.9% on antihypertensive medications, 21.3% with pre-existing CVD and 7.6 per 1000 person-years experienced the outcome over 7 years. Compared to SBP 120-129 mm Hg, the risk of CVD mortality was higher in SBP 140 mm Hg in patients with and without pre-existing CVD, the elderly and non-elderly. The hazard ratios (HR) were 1.27 (95% CI: 1.12-1.45), 1.87 (1.65-2.12), 1.49 (1.35-1.64) and 1.87 (1.55-2.25), respectively. Using DBP 70-79 mm Hg as reference, DBP &lt; 70 mm Hg was also associated with higher risk of CVD mortality in all patient groups, with corresponding HR 1.25 (1.12-1.39), 1.23 (1.11-1.36), 1.19 (1.10-1.29) and 1.54 (1.32-1.80), respectively. DBP 90 mm Hg was also associated with higher risk of CVD mortality in the elderly and those without pre-existing CVD. Conclusion: In patients with T2DM, higher SBP is associated with raised CVD mortality risk. Elevated DBP is independently associated with higher risk of CVD mortality albeit only in those without pre-existing CVD and the elderly. DBP &lt; 70 mm Hg is also associated with risk of CVD outcome although reverse causality cannot be ruled out.
Abstract 18846: A Noninvasive Smartphone Assessment of Aortic Arch Pulse Wave Velocity and Total Arterial Compliance
Authors: Soha Niroumandi, Derek Rinderknecht, Coskun Bilgi, Aaron Wolfson, Ajay Vaidya, Kevin S King, Niema M Pahlevan
Journal: Circulation (2023)

Introduction: Several clinical studies including a large multiethnic population (Dallas Heart Study) have shown that total arterial compliance (TAC) and aortic arch pulse wave velocity (PWV aa ) are predictors of cardiovascular disease (CVD) events. Dallas Heart Study also showed that PWV aa predicts brain white matter hyperintensity volume independent of cardiovascular risk factors. Recently, Intrinsic Frequency (IF) analysis of carotid pressure waveform from the Framingham Heart Study was used to predict heart failure (HF) events and CVD (Hypertension, 2021 PMID: 33390053). Aim: Our goal was to show the IF method can determine PWV aa and TAC when applied on carotid pulse waveforms obtained from a standard iPhone camera. Methods: The clinical cohort consisted of 120 individuals (40% women) with ages from 20-92 yrs (mean 53 ± 18), including 54 healthy and 66 patients with CVD (22 HF). Phase-contrast magnetic resonance imaging (PC-MRI) and carotid pressure tonometry data were used to compute TAC. PWV aa values were obtained using PC-MRI flow in ascending and descending aorta (not achieved in 1 patients). A custom Apple iPhone 5S application was used to obtain carotid pulse waves by holding the camera against the neck. IF parameters of iPhone waveforms (calibrated by cuff brachial pressures) were used in machine learning algorithms (IF-iPhone). The models of TAC and PWV aa were developed using 100 participants (99 for PWV aa ) and blindly tested on an additional 20 individuals. Results: In blind tests, iPhone-IF models showed Pearson correlations of r=0.89 and r=0.84 with the measured values of TAC and PWV aa , respectively (Fig.1). Conclusions: Assessment of PWV aa and TAC can be accurately achieved using an unmodified smartphone (iPhone). PWV aa evaluation with an iPhone can be used to identify, predict, and quantify risk of vascular brain damage. A Noninvasive iPhone-based method can be used in a clinical or home setting to routinely assess TAC in the general population or in HF.
Abstract 14638: NPA7: A Novel Designed Bispecific Peptide That Protects Human Cardiomyocytes Against Oxidative Stress Through the GC-A/Mas Receptor-KEAP1-NRF2 Pathway
Authors: xiaoyu ma, JC Malsawmzuali, Dante Moroni, Xiao Ma, Jeson Sangaralingham, John C Burnett
Journal: Circulation (2023)

Introduction: Excess cardiomyocyte oxidative stress is a major metabolic abnormality in HTN and its progression to HF. Thus, therapies that reduce oxidative stress in the heart may lead to a reduction in CVD related adverse outcomes such as HF and death. Recently, we bioengineered a bispecific peptide NPA7 that co-activates the protective GC-A/cGMP and MasR/cAMP pathways. Previously we showed that NPA7 possesses cardiorenal protective properties. However, the antioxidant effects of NPA7 within the heart is unknown. Hypothesis: NPA7 protects human cardiomyocytes against oxidative stress through the GC-A/Mas Receptor-KEAP1-NRF2 pathway. Methods: HCMs were pretreated with PBS or NPA7 (10 uM) followed by 400 uM hydrogen peroxide (H2O2) to induce oxidative stress. Intracellular ROS was measured by dihydroethidium (DHE) staining and protein levels of KEAP1 and NRF2 via western blot. The ratio of GSH/GSSG were determined by using commercial kit. mRNA levels of G6PD, GCLC, GCLM and GSS in HCMs, which represents antioxidant capacity, were determined by real-time PCR. For knockdown experiments, HCMs were transfected with the siRNA target GC-A and MasR for 24 h and then treated with NPA7 and H2O2 for another 20 h. Results: H2O2 increased DHE staining level, which indicated elevated intracellular ROS levels within HCMs. Notably, treatment with NPA7 decreased DHE level and increased the ratio of GSH/GSSG in HCMs with H2O2. Furthermore, NPA7 significantly increased the mRNA level of NRF2 target genes (G6PD, GCLC, GCLM, GSS) through NRF2 activation and KEAP1 degradation, indicating that NPA7 activates KEAP1-NRF2 pathway, the upstream pathway that regulate antioxidant gene expression, in HCMs. Moreover, these effects were eliminated if GC-A and MasR were silenced by siRNA, thus supporting the protective antioxidant role of both GC-A and MasR. Conclusions: The present study establishes an antioxidant action of NPA7, a novel bispecific designer peptide, on H2O2-induced oxidative stress by the dual targeting of GC-A and MasR through the KEAP1-NRF2 signaling pathway in HCMs. These results advance NPA7 as an innovative therapeutic strategy targeting oxidative stress related to CVD.
Abstract 16804: Nationalwide Trends and Predictors of Cardiogenic Shock in Takotsubo-Syndrome Related Admissions Stratified by Sex and Race: 2016-2019
Authors: Sai Gautham Kanagala, Prathistitha Mallapu, Dinesh Kumar Vuddandam, Durga Mounika Muvva, Alpha James, Raja Anvesh Reddy Adelli, Shantha Nallapothula, Swetha Chiluka, Vaibhavi Polavarapu, Leela Krishna prasad Mandadi, Devi Meghana Kotharu, Ankit Vyas, Akhil Jain, Rupak Desai
Journal: Circulation (2023)

Background: Sex and race disparities have been understudied in Takotsubo-Syndrome (TTS) patients with cardiogenic shock. The objective is to examine the recent trends and predictive factors associated with cardiogenic shock (CS) in patients with TTS, stratified by sex and race. Methods: We analyzed the admissions related to TTS from the National Inpatient Sample (NIS) 2016-2019 using the ICD-10-CM codes to examine the nationwide trends and predictors of cardiogenic shock taking into consideration the factors of sex and race. Results: Among a total of 96,405 TTS-related admissions, 5.9% (n=5,705) were diagnosed with CS. Individuals with CS were found to have a median age of 74 (with an interquartile range of 69-80), a higher proportion of males (21.2%), and a predominantly white racial background (83.2%), all of which were statistically significant(p&lt;0.001). Furthermore, patients diagnosed with CS experienced significantly longer hospital stays (median [IQR] 8 [4-14] vs. 4 [2-7]), incurred higher costs (median [IQR] 14.5 [8.1-28.7] vs. 5.6 [3.3-10.3]) and showed higher mortality (29.4% vs 5%) compared to those without CS (p&lt;0.001). The prevalence of all parameters depicted in Figure 1 showed a statistically significant increasing trend over the years(p&lt;0.05), except for Hispanics. Subgroup analysis revealed that males who had diabetes had significantly increased odds of developing CS [OR 1.57, CI 1.15-2.13, p=0.005]. Also, white individuals with diabetes had higher chance of CS [OR 1.21, CI 1.03-1.42, p&lt;0.05]. Conclusion: Recent trends indicate a rise of CS among TTS related hospitalizations with a notable impact on different demographics such as sex and race, particularly among Asian and pacific islanders. Additionally, in-hospital mortality in patients with CS was six times higher compared to the ones without CS.
Abstract 15557: A Retrospective Study of Clinical Pathways and Outcomes of Andexanet Alfa Administration for Reversal of Critical Bleeding or Urgent Surgery in Patients on Oral Direct Factor Xa Inhibitors
Authors: Mark Goldin, Kolton Smith, Ioannis Koulas, Tung Ming Leung, Mayuri Ravi, Sanjit Parhar, Sejal Shah, Kayla Floyd, Lori Ohanesian, Rachel Bain, Daniella Defonte, Kanta Ochani, Alex Spyropoulos
Journal: Circulation (2023)

Introduction: Andexanet is FDA approved for reversal of life-threatening bleeding from factor Xa (FXa) inhibitors rivaroxaban and apixaban and off-label for urgent surgical reversal. Data are lacking on processes to ensure prompt andexanet dosing. Hypothesis: Presentation-to-andexanet time depends on clinical, demographic, and hospital factors. Goals: To identify factors impacting presentation-to-andexanet time and post-andexanet adverse outcomes. Methods: We retrospectively studied patients at a 23-hospital system who received andexanet from November 3, 2019, to March 4, 2023. Abstractors manually coded demographics, comorbidities, anticoagulant use, andexanet indication, and clinical pathway time stamps. The primary outcome was presentation-to-andexanet time. Secondary outcomes were post-andexanet major thromboembolism or bleeding, and in-hospital mortality. Results: 110 patients were analyzed (mean age 77.4 years, 71.3% White). Most patients were on lower dose FXa inhibitors without antiplatelets; 77% had at least 2 vascular comorbidities. Andexanet was used most for intracranial hemorrhage (ICH) (80%); 7% of doses were for urgent surgery (Table 1). Median presentation-to-andexanet time was 219 minutes. Linear regression showed non-ICH bleeding was associated with greater time to andexanet dose. More post-treatment thromboembolism or bleeding occurred at tertiary academic hospitals (p = 0.02). In-hospital mortality did not differ among hospital types (Table 2). Conclusions: In a retrospective study, a non-ICH site was associated with greater median time to andexanet dose. More post-andexanet adverse events occurred at tertiary hospitals.
Abstract 16892: Statin Utilization and Recurrent Cardiovascular Disease Events in a Secondary Prevention Cohort of Older Adults
Authors: Deeksha Acharya, Aaron Walker, Jianhui Zhu, Floyd W Thoma, Agnes Koczo, Suresh R Mulukutla, Anum Saeed
Journal: Circulation (2023)

Introduction: The ACC/AHA guidelines recommend that patients with established ASCVD should be on high intensity statins for secondary prevention. Prior data suggests that older adults (&gt;75 years) are sub-optimally treated for both primary and secondary prevention of ASCVD events. We investigated guideline directed statin intensity (GDSI) use, associated LDL cholesterol levels and ASCVD outcomes in a cohort of older adults in a large healthcare network. Methods: EMR data was abstracted to assess statin prescriptions between 2010-2020 amongst adults with known ASCVD (CAD, ischemic stroke/TIA or PAD). Prescriptions of statins as GDSI (high intensity), &lt;GDSI (low/moderate intensity), and no statin were assessed and stratified by age groups. LDL-C levels across the follow up time were calculated. Cox regression models were used to assess HRs (Hazard Ratios) for repeat ASCVD event (MI and stroke/TIA) and all cause death, stratified by age and GDSI treatment. Results: Over ~5y follow up, amongst adults aged&gt;75 years (n=11,596), less than half (49.6%) were on GDSI and only ~54% older adults achieved LDL-c&lt;70mg/dL. Compared to GDSI use, older adults on &lt;GDSI had a greater incidence of recurrent MI [HR&gt;75y 1.59; 95% CI (1.30-1.95)], stroke [HR&gt;75 1.659; 95% CI (1.21-2.24)] and mortality [HR&gt;75 1.88; 95% CI (1.57-2.25)]; all p&lt;0.01 in &lt;GDSI group vs GDSI group. GDSI use had a greater reduction of MI and mortality in older adults than younger counterparts [Table 1]. Conclusions: In this contemporary healthcare network, GDSI use for secondary prevention and LDL-C&lt;70 mg/dL was suboptimal amongst all age groups. Any statin use conferred a greater reduction in MI and mortality amongst older adults &gt;75y. Systemic interventions for guideline implementation and optimal statin use in older adults with ASCVD should be explored further.
Abstract 159: Long-Term Survival and Neurological Follow-Up of Cardiac Arrest Survivors: Results From the French Multicentric Prospective Cohort the DESAC Study
Authors: Florence Dumas, Wulfran Bougouin, Marie-Cécile PERIER, Nathalie Marin, Cyril Goulenok, Antoine Vieillard-Baron, Jean-Luc Diehl, Stephane Legriel, Nicolas Deye, Pierrick Cronier, Sylvie Ricome, Frank Chemouni, Armand Mekontso-Dessap, Frankie BEGANTON, Eloi Marijon, Xavier Jouven, Jean-Philippe Empana, Alain Cariou
Journal: Circulation (2023)

Background: While short-term prognosis of cardiac arrest (CA) patients has been extensively studied, less is known regarding the mid- and long-term outcome of survivors. Aims: The aim of the DESAC study was to describe mid- and long-term survival and neurological status of CA survivors, and to assess the influence of pre- and intra-hospital therapeutic strategies on these outcomes. Methods: Between Jul 2015 and Oct 2018, patients over 18 years who were discharged alive from intensive care units in Paris and suburbs (France) after a non-traumatic CA were included and interviewed every 6 months during at least 24 months and up to 48 months in this multicentric study. Factors associated with Cerebral Performance Category (CPC) scale at 24 months were assessed with logistic regression, with CPC 1 or 2 level considered as a favorable neurological outcome. Trajectories of CPC were derived by mixed linear model in survivors with at least 3 evaluations. Results: Out of 593 survivors, 525 had a 24 months follow-up (mean age 57.6 +/-15.3, 79% men). CA occurred in public location in 251/525, with an initial shockable rhythm in 392/525. Prognostic factors independently associated with a favorable neurological outcome at 24 months were initial shockable rhythm (OR= 3.53 (1.65; 7.58)) and previous practice of sport (OR= 3.12 (1.20 ; 8.11)), whereas older age (OR per 10 years= 0.52 (0.40; 0.68)) and previous ischemic cardiomyopathy (OR= 0.34 (0.15 ; 0.77)) were poor prognostic factors. Therapeutic hypothermia or coronary procedures were not related to prognosis. Five trajectories of CPC could be derived among the 514 patients. Overall, 64% remained in CPC1, 13% in CPC2, 11% improved from CPC2 to CPC 12% died either early or lately (Figure 1). Conclusions: In this multicentric and prospective study, practice of sport and shockable rhythm were strongly associated with a favorable neurological recovery at 24 months. Furthermore, two thirds of the survivors remained in CPC 1 over time.