tbuckley/cabot-search huggingface dataset:
Abstract 13272: Acute Effects of Enhanced External Counterpulsation in Adults With Fontan Circulation
Authors: Fred M Wu, Amrit Misra, Christopher Valle, Madeline E Duncan, Sunil J Ghelani, Marie D Gerhard-Herman, Stuart R Lipsitz, Rahul H Rathod, Michelle Z Gurvitz, Michael N Singh, Anne M Valente
Journal: Circulation (2023)

Background: Patients who have undergone Fontan palliation for single ventricle CHD exhibit reduced cardiac output. Aims: To study the safety and acute hemodynamic effects of enhanced external counterpulsation (EECP) in a cohort of Fontan patients. Methods: Pilot study of adult Fontan patients recruited through the ambulatory clinic at a single, large-volume ACHD center. Patients underwent TTE and measurement of pulmonary blood flow (PBF), a surrogate for cardiac output, followed by 1 hour of EECP divided into 20-minute stages (80 mmHg, 160 mmHg, 240 mmHg). TTE and PBF measurement were repeated at each stage and 15-30 minutes after completion of EECP. Patients were monitored for symptoms throughout the visit. A repeated measures linear-mixed-model (robust to non-normality) was used to estimate the mean at each time point and to test for differences across time points. Results: There were 23 patients enrolled (52% male, 91% cis-gender, 74% White). Mean age at enrollment and at Fontan completion was 33.0 ± 7.8 years and 5.1 ± 4.1 years, respectively. Six patients (26%) had a pacemaker. Twenty-two (96%) completed a full hour of EECP. Pressure was reduced in the third stage for 3 patients due to discomfort. No patients reported chest pain or increased dyspnea during EECP. PBF was increased at each stage of EECP compared to baseline and returned to baseline post-EECP (Fig. 1). There was a small qualitative improvement in ventricular systolic function in the second and third stages of EECP compared to baseline (160 mmHg: p=0.048; 240 mmHg: p=0.024). O 2 saturation was increased at each stage of EECP compared to baseline (baseline: 93.0%, 80 mmHg: 94.3% [p=0.008], 160 mmHg: 94.6% [p=&lt;0.001], 240 mmHg: 94.6% [p=&lt;0.001]). Mean arterial pressure and heart rate did not change. Conclusions: EECP is well-tolerated in adult Fontan patients and acutely improves PBF at pressures as low as 80 mmHg. Further study is warranted to explore long-term therapeutic effects of EECP in these patients.
Abstract 14483: Myeloid Cell Derived IL1b Contributes to Pulmonary Vascular Remodeling in Heart Failure With Preserved Ejection Fraction
Authors: Vineet Agrawal, Jon Kropski, Jason J Gokey, Elizabeth Kobeck, Matthew Murphy, Katherine T Murray, Niki Fortune, Christy Moore, David Meoli, Ken Monahan, Yan Ru Su, Thomas Blackwell, Deepak K Gupta, Megha Talati, Santhi Gladson, Erica J Carrier, James West, Anna R Hemnes
Journal: Circulation (2023)

Introduction: Pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is a common and highly morbid syndrome, but mechanisms driving PH-HFpEF are poorly understood. Hypothesis: We sought to determine whether a well-accepted murine model of HFpEF also displays features of PH, and we sought to identify pathways that might drive early remodeling of the pulmonary vasculature in HFpEF. . Methods: Eight-week-old male and female C57BL/6J mice received either L-NAME and high fat diet (HFD) or control water and diet for 2, 5, and 12 weeks. Db/db mice were studied as a second model of HFpEF. Early pathways regulating PH were identified by bulk and single cell RNA sequencing. Findings were confirmed by immunostain in lungs of mice or lung slides from clinically performed autopsies of PH-HFpEF patients. ELISA was used to verify IL1β in mouse lung, mouse plasma, and also human plasma from PH-HFpEF patients obtained at the time of right heart catheterization. Clodronate liposomes and an anti-IL1β antibody were utilized to deplete macrophages and IL1β, respectively, to assess their impact on pulmonary vascular remodeling in HFpEF in mouse models. Results: L-NAME/HFD treated mice developed PH, small vessel muscularization, and right heart dysfunction. Inflammation-related gene ontologies were over-represented in bulk RNA sequencing analysis of whole lungs, with an increase in CD68 + cells in both murine and human PH-HFpEF lungs. Cytokine profiling showed an increase in IL1β in mouse and human plasma. Finally, clodronate liposome treatment in mice prevented PH in L-NAME/HFD treated mice, and IL1β depletion also attenuated PH in L-NAME/HFD treated mice. Conclusions: We report a novel model for the study of PH and right heart remodeling in HFpEF, and we identify myeloid cell derived IL1β as an important contributor to PH in HFpEF.
Abstract 13270: Social Deprivation Index and Cardiovascular Disease Risk Among 2.5 Million Patients in the US
Authors: Ebenezer K Aryee, Chiadi E Ndumele, Sadiya S Khan, Deidra Crews, Yingying Sang, Morgan Grams, Shoshana Ballew, Kuni Matsushita, Josef Coresh
Journal: Circulation (2023)

Background: Neighborhood-level social determinants of health (SDOH) impact cardiovascular disease (CVD) risk. However, limited data are available from large, multi-ethnic, national samples with CVD risk factors on how place-based SDOH independently relates to CVD risk, and on whether accounting for place-based SDOH attenuates race/ethnicity differences in CVD risk. Methods: We studied 2,538,811 patients free of prior CVD in the Optum Labs Data Warehouse (OLDW). Billing addresses were geocoded to derive social deprivation index (SDI, deciles 0 to 10 as a composite measure of poverty, education, employment, home rental &amp; crowding, single-parent households and no car ownership) at the zip code level. SDI was compared by race/ethnicity, as coded in the electronic health record. Multivariable Cox models quantified the adjusted relative hazard of incident CVD (using hospitalization discharge codes) associated with linearly modeled SDI in the overall population and stratified by race/ethnicity. We also assessed race/ethnicity differences in incident CVD risk before and after adjustment for SDI and CVD risk factors. Results: Mean age was 52 years, 57% were female, with a range of health insurance (75% commercial, 15% Medicare, 2.5% Medicaid). The highest SDI was seen among Black and Hispanic patients. SDI was associated with increased risk of CVD in all race/ethnicity groups (Table). Race/ethnicity differences in CVD risk were attenuated when adjusted for SDI and CVD risk factors (e.g., HR for HF in Black vs White patients decreased from 1.59 [95% CI: 1.47-1.72] adjusted for age and sex, to 1.29 [95% CI: 1.18-1.40] further adjusted for SDI, to 1.09 [95% CI: 1.00-1.19] adjusted for SDI and risk factors). Conclusions: Social deprivation levels are associated with CVD risk independent of traditional risk factors. Accounting for disparities in SDI, which reflect both present and past influences, attenuates differences in CVD risk associated with race and ethnicity.
Abstract 13651: Pembrolizumab Associated Myocarditis, Myasthenia Gravis, and Myositis
Authors: Grace Alexander, Erin Sternhagen, Bilal Rahim, Matthew Jergenson, Shareef Mansour
Journal: Circulation (2023)

Case: A 71 year old man presented with acute generalized muscle weakness, double vision, sagging eye lids, weakness with swallowing, shortness of breath, and dark urine. History was notable for stage IV non-small cell lung cancer with second dose of pembrolizumab therapy completed 12 days earlier. Exam showed bilateral ptosis and muffled speech. He had increased work of breathing, tachypnea, 3/5 strength in the bilateral lower extremities, and 5/5 strength in the upper extremities. His initial NIF was -25. Labs were notable for troponin of 1532, CK 16229, ESR 100, CRP 8.8, ALT 225, and AST 648. EKG revealed a new right bundle branch block and left posterior fascicular block. TTE showed EF of 65% without regional wall motion abnormalities. Cardiac MRI showed mildly elevated T1 and T2 relaxation times, suggestive of diffuse myocardial edema and inflammation without delayed gadolinium enhancement. He was treated with high dose steroids, fluid resuscitation, IVIG, and briefly pyridostigmine. On hospital day 8, he was found to have complete AV block with junctional escape rhythm. He had urgent placement of a temporary pacemaker. He was started on abatacept, ruxolitinib, and oral prednisone. Over the next 14 days he made gradual improvement. Discussion: While ICI-associated myocarditis is rare, it is worth investigating due to the high mortality. The clinical presentation can range from asymptomatic troponin elevations to cardiogenic shock and ventricular arrhythmias/AV block. Diagnosis requires a high index of suspicion and multiple diagnostic modalities, including ECG, echocardiography, serum biomarkers, and often cardiac MRI and endomyocardial biopsy. There is a large overlap between myocarditis and myositis. The mainstay treatments of ICI-induced myocarditis include holding the offending immune-checkpoint inhibitor, high-dose corticosteroids, and guideline-directed medical therapy for associated heart failure or arrhythmias. Abatacept, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) immunoglobulin fusion protein, and ruxolitinib, a JAK 1/2 inhibitor, have recently been suggested as a novel combination to reduce mortality from ICI-associated myocarditis with concomitant myositis.
Abstract 18121: Gaps in Initiation of Evidence-Based Medical Therapies in Patients With Ischemia With Nonobstructive Coronary Artery Disease
Authors: Juhi Ramchandani, Chirag Shah, Luke Landrigan, Harshvardhanan Zala, Unai Miguel Andres, Ronald Mastouri, Balaji Tamarappoo
Journal: Circulation (2023)

Introduction: Ischemia with nonobstructive coronary artery disease (INOCA) is associated with major adverse cardiovascular events (MACE) due to atherosclerotic plaque progression, rupture of high-risk plaque and microvascular dysfunction. While there is evidence for use of ACE inhibitors/ARBs and statins to reduce MACE in patients with coronary artery disease (CAD), gaps in implementation of maximal medical therapy in patients after diagnosis of INOCA is not well described. We hypothesize that cardioprotective medications may be underutilized in patients with INOCA. Methods: Patients (n=443) with ischemic symptoms associated with ECG changes or troponin rise, no history of CAD and with nonobstructive CAD on noninvasive or invasive coronary assessment between 2010-2021 at Indiana University Health, Indianapolis, were included in this study. Results: In 226 women and 217 men with mean age 58.5 yrs, 315 underwent invasive angiography and 128 coronary CTA. Compared to baseline, initiation rates of cardioprotective agents were low after INOCA diagnosis for statins (37.9%) and aspirin (ASA, 36.1%) (Figure 1A). Among eligible patients, statins and ASA were underutilized in 42% and 44% respectively. There were no statistically significant differences in prescribing patterns of ASA and statin based on gender or race (Figure 1B). Conclusions: There are significant gaps in the prescription of cardioprotective medications including statins, ASA, ACEI/ARB and beta blockers in patients with INOCA at a quaternary care hospital. If this pattern is similar to the rest of the country, the factors associated with underutilization of these medications needs to be explored further.
Abstract 14692: Clonal Hematopoiesis Driver Mutations Have Disparate Effects on Macrophage Cytokine Profiles and Only Modestly Drive Atherogenesis at Pathophysiological Levels
Authors: Paul Carter, Siddhartha Kar, Lauren Kitt, Nichola Figg, Pedro Quirós, Ang Zhou, Stephen Burgess, George Vassiliou, Peter Libby, Martin Bennett, Murray C Clarke
Journal: Circulation (2023)

Background: Clonal hematopoiesis (CH) is characterized by expansion of hematopoietic stem cells due to somatic mutations in leukemia-associated genes. CH is associated with increased mortality, attributed to cardiovascular disease (CVD) driven by increased IL-1β from clonal macrophages. However, different CH-driver mutations perturb diverse genes with distinct functions and reports of IL-1β release from mutant macrophages are discordant. Furthermore, directionality of the association between CH and CVD is not established. Hypothesis: We hypothesized that mutations of common CH-driver genes have disparate effects on macrophage cytokine profiles and atherogenesis. We also hypothesized that atherosclerosis-driven systemic inflammation promotes clonal expansion. Methods/Results: We characterised cytokine expression in LPS-treated murine bone marrow-derived macrophages (BMDMs) harboring CH-driver mutations ( Tet2 , Dnmt3a , or Jak2 ). Transcript level of Il1a , Il1b and Il6 was increased ~3-5 fold in Tet2 -/- and Dnmt3a -/- BMDMs, but only ~1.5-2 fold with heterozygotic loss, which mimics more closely patients with CH. Notably, Tet2 -/- BMDMs (but not Dnmt3a or Jak2 ) release more IL-1α/β, accompanied by increased Asc specks and caspase-1 activity, implying heightened NLRP3 inflammasome activation. In murine chimera models of CH, Tet2 -/- and Tet2 +/- cells (but not Dnmt3a or Jak2 ), expand under the steady state. Clonal dynamics were unaffected by systemic inflammation via exogenous IL-1α, or high fat diet-induced atherogenesis in Ldlr -/- recipients. Atherosclerotic plaques in murine CH models at 12 weeks are only mildly increased with heterozygotic Tet2, Dnmt3a, or Jak2 mutations (10-20%). Observational and Mendelian randomisation analyses of UK BioBank did not reveal bidirectional associations between CH and atherosclerosis. Conclusions: We demonstrate augmented NLRP3 inflammasome activation in Tet2 -/- BMDMs and disparate effects of different CH mutations on cytokine profiles. We find no evidence for atherosclerosis or systemic inflammation driving clonal expansion. Thus, the pathogenesis of CH-driven disease should be treated as different entities for each mutation and likely involves overlapping or distinct mediators.
Abstract 17529: Controlling Nutritional Status (CONUT) Score Predicts Adverse Events in Patients With Chronic Heart Failure Following Cardiac Resynchronization Therapy
Authors: Yuma Ono, Taisuke Harada, Hidekazu Kondo, Kunio Yufu, Tetsuji Shinohara, Yasushi Teshima, Naohiko Takahashi
Journal: Circulation (2023)

Introduction: Malnutrition and cachexia have been reported to be associated with poor outcomes in patients with chronic heart failure (CHF). Hypothesis: This study aimed to investigate the association between malnutrition determined by the Controlling Nutritional Status (CONUT) score and adverse events in patients with CHF after cardiac resynchronization therapy (CRT). Methods: This retrospective study evaluated 134 patients (90 male, mean age 70.6 ± 9.7 years; 31 (23%) old myocardial infarction, 57 (43%) dilated cardiomyopathy, 46 (34%) others) who underwent CRT implantation between 2004 and 2020 and were followed for at least one year after the operation (mean, 1070 ± 649 days). CONUT score was calculated in those patients before the CRT implantation. Patients with CONUT score of 0 - 4 (n = 106) were allocated to the preserved nutrition group, and those with CONUT score 5 - 12 (n = 28) were allocated to the malnutrition group. The primary endpoint was hospitalization for heart failure. The secondary endpoint was ventricular arrhythmias including both ventricular tachycardia and ventricular fibrillation, requiring anti-tachycardia pacing, cardioversion. Results: During the follow-up period, hospitalization for heart failure occurred in 55 patients (41%). Ventricular arrhythmias occurred in 31 patients (23%), and 15(48.6%) patients required cardioversion. Kaplan-Meier survival analysis showed a higher incidence of hospitalization for heart failure (log-rank 6.55; P = 0.011) and ventricular arrhythmias (log-rank 6.55; P = 0.011) in the malnutrition group. Cox proportional hazards regression analysis revealed that malnutrition group had a higher incidence of hospitalization for heart failure (hazard ratio 2.11; 95% CI:1.14 - 3.70, P = 0.018) and ventricular arrhythmias (hazard ratio 2.53; 95% CI:1.17 - 5.19, P = 0.020). Conclusions: Malnutrition determined by the CONUT score predicts adverse events in patients undergoing CRT implantation.
Abstract 14574: Trends in the Utilization of Sacubitril/Valsartan by Cardiologists: A Safety-Net Hospital Experience
Authors: Khalid Sawalha, Andrew Smith, Nicholas Norgard, Angel Lopez-Candales
Journal: Circulation (2023)

Background: Sacubitril/Valsartan has gained significant momentum regarding management of heart failure. In the latest 2022 HF guideline, Sacubitril/Valsartan is recommended as a first-line treatment and to replace well-tolerated ACEi/ARB’s. We decided to evaluate current utilization trends with regards to prescription of Sacubitril/Valsartan at our safety-net hospital. Methods: For this retrospective study,a chart review identified Sacubitril/Valsartan use in a total of 769 patients,which was catalogued by drug dose, division use, and prescriber specialty at University Health Truman Medical Center in Kansas City, Missouri from October 1, 2021 thru October 31, 2022. Results: Of the 769 patients prescribed Sacubitril/Valsartan, 497 patients were prescribed the 24 mg/26 mg dose, 193 patients were on 49 mg/51 mg dose, and 79 patients were provided a 97 mg/103 mg dose (Figure 1). Cardiologists were only involved in 23% of all Sacubitril/Valsartan prescriptions while ancillary staff providers including nurse practitioners, physician assistants and pharmacists representing the predominant number of healthcare professionals (50%) prescribing Sacubitril/Valsartan (Figure 2). Conclusion: Despite the robust evidence supporting the benefit of using Sacubitril/Valsartan in HF and the unique opportunity that Cardiologists have in taking ownership in optimizing HF management; our data seems to suggest that prescription rates of Sacubitril/Valsartan by Cardiologists at our institution remains low when compared to other specialties. This may contribute to an undertreatment of high-risk HF patients.
Abstract 15960: Mortality Differences Among Myocardial Injury Subtypes in Acute COVID-19, the Omicron Wave Was Different
Authors: Benjamin A Satterfield, Ozan Dikilitas, Lubna Alhalabi, Bernard J Gersh, Iftikhar J Kullo
Journal: Circulation (2023)

Introduction: Hospitalization for COVID-19 is often associated with myocardial injury (elevated cardiac troponin [cTn]). In the initial pandemic waves, patients with myocardial injury had increased likelihood of cardiovascular complications and inpatient mortality; however, the differences in impact of distinct subtypes of myocardial injury on mortality is unclear. In addition, little is known about how these outcomes compare with the subsequent, milder, Omicron wave. Methods: Utilizing Mayo Clinic enterprise patients we developed algorithms based on diagnostic/procedural codes, cTn levels, and temporal relationships to positive COVID-19 PCR tests, to determine 5 common subtypes of myocardial injury: stress cardiomyopathy, myocarditis, pericarditis, pulmonary embolism, and myocardial infarction. We examined hospitalized adults with COVID-19; those with elevated cTn designated as cases and others as controls. We fitted Cox models using the following covariates: spline transformed age, sex, race, ethnicity, index date and clinical comorbidities. Patients were analyzed based on admission dates coinciding with either the Alpha-Delta or Omicron waves. Results: Across both wave cohorts, hospitalized patients with acute COVID-19 complicated by myocardial injury had an increased risk of mortality compared to those without ( Figure ). Patients with one of the 5 subtypes examined tended to have higher risk than those in the “other myocardial injury” category. Admission during the Omicron wave, compared to the Alpha-Delta waves, tended to have higher mortality risk in all subtypes except myocarditis. Conclusions: Our algorithms successfully identified subgroups of myocardial injury in patients hospitalized with acute COVID-19 leading to stratification of mortality risk. Surprisingly, among hospitalized patients during the Omicron wave, myocardial injury of most subtypes was tended to have increased risk of mortality compared to the Alpha-Delta waves.
Abstract 13461: Early Vascular Aging is Associated With Early Cardiac Aging, Upregulation of Left Ventricle Pro-Fibrotic and Inflammatory Genes and Memory Decline in Aged Dahl Salt-Sensitive Rats
Authors: Yulia N Grigorova, Ondrej Juhasz, Jeffrey M Long, Ross A McDevitt, Valentina I Zernetkina, Christopher H Morrell, Wen Wei, Peter R Rapp, Alexei Y Bagrov, Edward G Lakatta, Olga V Fedorova
Journal: Circulation (2023)

Introduction: Blood pressure (BP) begins to increase early in life in Dahl salt-sensitive rats (DSS) that consume a normal salt (NS) diet. Epidemiologic studies have shown that early vascular aging (EVA) is associated with central arterial stiffening (CAS) and hypertension, which develop earlier in life than expected in general population and contribute to cognitive impairment later in life. Hypotheses: (i) DSS rats will develop EVA earlier in life on NS diet, and with advancing age will exhibit early CV aging; (ii) In DSS, CV remodeling and CAS are implicated in memory decline. We tested these hypotheses using a longitudinal repeated measure design in DSS and their parental breed Sprague-Dawley rats (SD) at 3- &amp; 12-mo of age. Methods: Male SD and DSS were kept on NS diet (0.5% NaCl; n=8/group) for entire experiment. Repeated measures of systolic BP (SBP), pulse wave velocity (PWV; an index of CAS), echocardiography, and non-repeated measures of Morris water maze (MWM) to test spatial memory, aortic collagen, elastin (histochemistry), and left ventricle (LV) mRNA expression (qPCR) were assessed at 3- &amp; 12-mo. Data analyses: linear mixed-effect 2-way ANOVA, t-test &amp; linear regression (LR) modeling. A 2-sided p&lt;0.05 was considered significant. Results: SBP, PWV, aortic weight, wall thickness and collagen/elastin ratio were higher in DSS-3 vs. SD-3, and in DSS-12 vs. DSS-3. RWT and LV expression of pro-fibrotic, inflammatory and senescence genes were higher in DSS-12 vs. DSS-3 and vs. SD-12 (Table). DSS-12 spent more time to find a hidden platform in MWM vs. SD-12; their impaired spatial hippocampal memory was positively associated with PWV and LV mass by LR analysis. Conclusions: EVA, indexed as higher BP, PWV and aortic remodeling was associated with early CV aging, manifested by activation of LV senescence, inflammatory and pro-fibrotic genes and by higher rates of age-associated changes in BP, RWT and LV mass in DSS vs. SD. In DSS, early CV aging was associated with memory decline.