tbuckley/cabot-search huggingface dataset:
Abstract 12041: Coronary Artery Calcium and All-Cause Mortality in the Multicenter Aids Cohort Study: MACS
Authors: Takahiro Suzuki, Sabina Haberlen, Tess E Peterson, Frank Palella, Matthew Budoff, Mallory D Witt, Jared W Magnani, Wendy S Post
Journal: Circulation (2023)

Introduction: People living with HIV (PLWH) have more subclinical cardiovascular disease than people without HIV (PWOH), but few studies have evaluated risk for mortality based on coronary artery calcium (CAC) among this population. Purpose: This study aimed to determine the association between CAC and all-cause mortality among male PLWH and PWOH and to identify a potential interaction with HIV serostatus. Methods: The study population was derived from the MACS, a US prospective observational cohort study including male PLWH and PWOH. Participants underwent cardiac non-contrast computed tomography from July 2004 to November 2013. Men with atrial fibrillation, coronary heart disease, or coronary revascularization were excluded. Cox proportional hazards model was used to calculate adjusted hazard ratios [aHR] for all-cause mortality among men with vs. without baseline CAC (Agatston score&gt;0) and per standard deviation (SD) increment in continuous Agatston score [log (CAC+1)], controlling for demographic and cardiac risk factors. CAC differences by HIV serostatus were evaluated using multiplicative CACхHIV interaction terms. Results: Among 1344 males (mean age 50 years, CAC prevalence 46%, 823 (61%) PLWH), we observed 110 deaths (13%) among PLWH and 41 deaths (8%) among PWOH during the follow-up period (median: 13.4 years). Among PLWH, 62% had an undetectable plasma HIV viral load, the median CD4 cell nadir was 284 cells/μL, and 17% had a history of clinical AIDS. The age-adjusted mortality rate was 13.5 (95% CI: 11.0-16.5) among PLWH and 7.8 (5.4-10.9) among PWOH per 1000 person-years. CAC presence was associated with all-cause mortality among all participants (aHR=1.47, 95% CI: 1.02-2.11, p=0.04), and among PLWH (aHR=1.61, 1.04-2.47, p=0.03). In PWOH, we found no significant association (aHR=1.27, 0.63-2.59, p=0.50), although the interaction was not significant (p= 0.49). Higher log (CAC+1) was also associated with all-cause mortality among all participants (aHR=1.37 per SD, 1.15-1.63, p&lt;0.001) and among strata (PLWH, aHR=1.40, 1.13-1.73, p=0.002; and PWOH aHR=1.38, 1.00-1.91, p=0.049). Conclusion: CAC predicts all-cause mortality in a large cohort of PLWH and PWOH, with no significant difference in this association by HIV serostatus.
Abstract 14924: SM22-Cre-Mediated SOCS3 Deficient Mice Exhibit Pericardial Fibrosis, Diastolic Dysfunction, and Increased Mortality Rates Due to Augmented Activation of STAT3 in Fibroblasts
Authors: Toshiyuki Yanai, Mai Yamamoto, Hideo Yasukawa, Kodai Shibao, Daiki Akagaki, Kota Okabe, Tatsuhiro Shibata, Shoichiro Nohara, Jinya Takahashi, Tomoko Sasaki, Kanako Shima, Yoshihiro Fukumoto
Journal: Circulation (2023)

Background: Suppressor of cytokine signaling-3 (SOCS3) is a cytokine-inducible potent negative regulator of STAT3 signaling pathway. Here, we aimed to determine whether SOCS3 in non-cardiomyocytes would play a role in cardiovascular pathophysiology. Methods and Results: To investigate the role of SOCS3 in non-cardiomyocytes, we generated conditional knockout mice by crossing SOCS3-flox mice with SM22-α-Cre mice (SM22-SOCS3-KO mice). Mortality rates in the SM22-SOCS3-KO mice was significantly higher than that in the wild-type mice (WT). Heart weight to body weight ratio was significantly increased in SM22-SOCS3-KO mice compared with WT at 12 months of age. Echocardiographic analyses revealed that SM22-SOCS3-KO mice showed significantly increased left ventricular diastolic dysfunction compared with WT from 12 months of age. Sirius-red staining revealed that thickness of pericardium and cardiac interstitial fibrosis in SM22-SOCS3-KO mice were markedly greater compared with WT mice at 12 months of age. Western blot analyses showed that phosphorylated STAT3 was significantly increased in SM22-SOCS3-KO hearts compared with WT mice at 12 months of age. PCR array analysis revealed that the expression of pro-fibrotic ctgf , pdgf , and TGF-beta family genes including tgf-beta1 , tgf-beta2 , and tgf-beta3 , were significantly higher in SM22-SOCS3-KO hearts than those in WT at 6 months of age. We also found that circulating interleukin-6 concentration was significantly higher in SM22-SOCS3-KO mice compared with WT mice at 12 months of age. After interleukin-6 administration, in the heart tissue from SM22-SOCS3-KO mice, coimmunostaining of phosphorylated STAT3 and ER-TR7 revealed that STAT3 activation occurred in fibroblasts in the coronary arterial adventitia and pericardium. Conclusion: Thus, SM22-Cre-mediated SOCS3 deletion induces higher mortality rates, increased pericardial fibrosis, cardiac interstitial fibrosis, and increased diastolic dysfunction in aging mice, possibly through the increased activation of STAT3 in fibroblasts.
Abstract 14978: Using a Machine Learning Risk Score to Predict Outcomes in Patients Undergoing LVAD Implantation: An Analysis of the INTERMACS Database
Authors: Sonya John, Jin Joo Park, Avi Yagil, Claudio Campagnari, Barry Greenberg, Eric Adler
Journal: Circulation (2023)

Background: Left ventricular assist device (LVAD) implantation is a viable treatment option for end-stage heart failure patients. Despite its benefits, outcomes of LVAD surgery can vary significantly, underscoring the importance of accurately assessing patients' risk prior to the procedure. MARKER-HF is a mortality risk model that utilizes machine learning algorithms to predict outcomes in HF patients. Aim: We assessed the predictive accuracy of MARKER-HF in patients undergoing LVAD implantation and determined whether it offered prognostic information beyond the INTERMACS profile. Methods: We calculated the MARKER-HF score in 25,365 patients from the INTERMACS database who underwent LVAD implantation between 2006 and 2020 and divided the population into 4 risk groups based on their score (low &lt;-0.2; moderate: -0.2 - 0; high: &gt;0 - 0.2; very high: &gt;0.2). The outcomes of interest were in-hospital and post-discharge 1-year mortality. Results: There was a negative correlation between the MARKER-HF score and INTERMACS profile (Pearson r = -0.348). MARKER-HF score exhibited a wide distribution within each INTERMACS profile. During the index hospitalization, 1383 (5.5%) patients died. The in-hospital mortality increased steadily with a higher MARKER-HF score, ranging from 2.9% in low to 13.8% in very high-risk groups, while it decreased with a higher INTERMACS profile. When combining the MARKER-HF and INTERMACS profile, we identified both patients with the lowest (2.6%) and the highest in-hospital mortality (16.1%). In a Cox-proportional hazard regression analysis adjusting for both MARKER-HF and INTERMACS profile, only the MARKER-HF score was significantly associated with increased post-discharge mortality (hazard ratio: 1.25, P&lt;0.001), but not INTERMACS profile (P=0.847). Conclusion: The MARKER-HF score is a simple non-invasive tool that can assist with optimal decision-making and can add additional information beyond the INTERMACS classification.
Abstract 13443: Dead Antegrade Fast Pathway: A Dilemma for Atrioventricular Nodal Re-Entry Tachycardia Ablation
Authors: Ninad Nadkarni, Emmanuel Fohle, Scott Pham
Journal: Circulation (2023)

Background: Catheter ablation is the first-line treatment option for symptomatic atrioventricular nodal re-entry tachycardia (AVNRT). Ablation of the slow pathway is preferred over the fast pathway in Typical AVNRT, given that it has a lower risk of heart block. Still, baseline conduction abnormalities and findings on the Electrophysiology (EP) study can alter the ablation strategy. Case: We report a case of a 61-year-old male who was referred to EP clinic for symptomatic suspected AVNRT. His baseline electrocardiogram (EKG) showed normal sinus rhythm with PR prolongation, right bundle branch block, and left anterior fascicular block. EP study was performed, which showed prolonged AH interval with normal HV interval (Figure 1). Typical AVNRT was induced with a premature atrial complex; there was no AV nodal jump before the tachycardia, but it had a long AH interval (Figure 2). There was no evidence of pre-excitation. Discussion: Since there was no antegrade conduction through the fast pathway, conventional slow pathway ablation was not viable as it would make the patient pacemaker (PM)-dependent. Even ablating the fast pathway, though not PM-dependent, would still put him at risk for complete heart block, especially when his antegrade conduction via the slow pathway was unreliable. Hence PM was discussed with the patient before ablation. The fast pathway was mapped and ablated (Figures 3, 4, and 5) without complication, and PM was implanted. Conclusion: This case emphasizes the role of fast pathway ablation in symptomatic AVNRT in patients with conduction abnormalities and the importance of EP study to see the need for PM post-ablation.
Abstract 12492: Relation of Medical and Social Determinants of Health to Use of Guideline-Directed Medical Therapy for Heart Failure With Reduced Ejection Fraction in the All of Us Research Program
Authors: Trinh K Do, Kyrillos Grace, Yufan Gong, Divya Devineni, Dawn Lombardo, Nathan D Wong, Andy Lee
Journal: Circulation (2023)

Background: HFrEF is associated with significant morbidity and mortality. The standard of care is guideline-directed medical therapy (GDMT) consisting of evidence-based pharmacological interventions which have demonstrated improved outcomes in HFrEF. However, paltry adherence to GDMT remains an ongoing challenge. We examined in US adults the relationship between social determinants of health (SDOH), demographics, and risk factors on GDMT adherence for HFrEF. Methods: The NIH All of Us Research Program started in May 2018 with the goal of enrolling over 1 million US residents. Over 315,000 participants have shared electronic health records, physical measurements, surveys, and lab results. Demographics, risk factors, and SDOH measures were captured for HFrEF in US adults 18 years or older. Patients with HFrEF who were on quadruple therapy (ACE-inhibitor/angiotensin receptor/combination angiotensin receptor-neprilysin inhibitor, beta-blocker, SGLT2 inhibitor, mineralocorticoid antagonist) were compared to those on fewer. Multiple logistic regression analyses were conducted to examine the association between risk factors/SDOH measures and medical therapy optimization. Results: In the All of Us data, 6049 patients were identified with HFrEF. Of those patients, 5838 (97%) patients were on less than 4 GDMT, while 210 (3%) patients were on quadruple therapy. Multiple logistics regression showed participants with ASCVD, and diabetes had higher odds (95% CI) of being on quadruple therapy, 2.19 [1.28, 3.99] and 9.07 [4.88, 18.84], respectively, while hypertension had lower odds (0.64 [0.43, 0.95]). Race, income, education, and health insurance types did not predict medical therapy optimization. Conclusion: Various cardiovascular conditions were associated with higher odds of being on quadruple therapy. However, sociodemographic factors did not show a correlation of predicting the odds of achieving maximal medical therapy.
Abstract 18240: Co-Creating Atrial Fibrillation Patient Education Videos by Combining Diverse Patient Feedback, Clinician Peer Review, and ChatGPT Content Analysis to Enhance Guideline-Directed Care Implementation
Authors: Nino Isakadze, Natalie Horstman, Chang Kim, Francoise A Marvel, Stephney Blair, Courtney Eddy, Sukhbir Randhawa, Anthony Sky Ng-Thow-Hing, Xavier Cheng, Erin Spaulding, Mansi Nimbalkar, Hugh G Calkins, David D Spragg, Seth S Martin
Journal: Circulation (2023)

Introduction: Strong evidence supports that (1) risk factor modification (RFM), (2) stroke prevention, (3) rhythm and (4) rate control are the four pillars of atrial fibrillation (Afib) management. Critical gaps exist in the clinical implementation of these four pillars. Patients and clinicians have identified lack of patient education as a major contributor to the failure of implementing guidelines in patient care. Methods/Results: We previously identified topics of patient education spanning the four pillars of Afib management via human centered design sessions with diverse patients (n=8, median age 69 (IQR 58-78), 50% women, 25% Black, 13% Asian), and clinicians (n=8). Qualitative analysis of the discussions with patients and clinicians was performed to identify desired topics of patient education. After identification of the key topics, we constructed scripts for patient education in an inclusive and iterative manner including physicians, nurses, and technologists (n=10). We then leveraged OpenAI’s ChatGPT - 3.5 artificial intelligence tool to adjust the reading level of the scripts to a 6 th grade reading level to ensure equitable delivery of education. The scripts were again revised for content accuracy. We then used an animated video creation platform (Vyond, San Mateo, CA) to create twenty videos covering the topics of stroke prevention, lifestyle modification, rhythm, and rate control. The videos will be part of a virtual Afib management intervention to be evaluated in a RCT. Conclusions: We have successfully co-created Afib educational videos using input from diverse patients and clinicians with assistance from the artificial intelligence tool ChatGPT. Patient education materials co-created with diverse patients and clinicians have the potential to promote equity in guideline-directed care delivery. We will evaluate the efficacy of the educational videos as part of a virtual Afib management program in Afib guideline implementation in a RCT.
Abstract 18308: Effective Atomic Number and Electron Density Number in the Infarcted Myocardium Were Significantly Lower Than Normal Group and Non-Infarcted Myocardium Using the Latest Spectral CT
Authors: Nobusada Funabashi, Shin Akaza, Atsushi Shukuya, Hiroki Asano
Journal: Circulation (2023)

Introduction: Spectral CT with a dual layer detector can be used to acquire new parameters, such as effective atomic (EAN) and electron density number (EDN). Hypothesis: The EAN and EDN obtained from the latest spectral CT with a dual-layer detector in infarcted myocardium were lower than the myocardial in the normal group and non-infarcted myocardia of patients with previous myocardial infarction (MI). Methods: This retrospective study comprised two groups of patients: those with previous MI (MI group; n = 20; mean age, 73±7 years) and those with clinically suspected coronary artery diseases, no significant stenosis in the coronary arteries, and a normal ECG (normal group; n = 146; age 55±14 years). All patients underwent cardiac spectral CT (7500; Philips) with a dual-layer detector. The EAN and EDN were measured in the interventricular septum (IVS), left ventricle (LV) anterior wall of the (LVAW), and LV lateral wall (LVLW) within a 1.0 mm2 circle at the LV inflow level in axial images during the non-contrast phase and early phase (with a contrast agent). Results: During the non-contrast phase, the EAN in the infarcted myocardium was significantly lower than those in the normal group (P &lt; 0.01) and the non-infarcted myocardia in the MI group (P &lt; 0.05). During the early phase, the EAN in the infarcted myocardium was also significantly lower than those in the normal group (P &lt; 0.01) and the non-infarcted myocardia in the MI group (P &lt; 0.05). During both phases, the EDN in the infarcted myocardium was significantly lower than those in the normal group (P &lt; 0.01) and the non-infarcted myocardia in the MI group (P &lt; 0.05). Conclusion: During both phases, the EAN and EDN in the infarcted myocardium were significantly lower than those in the normal group and the non-infarcted myocardia in the MI group. Using this novel CT approach and the data from the non-contrast phase may aid in detecting abnormal characteristics (such as reduced blood flow, fibrotic changes, or inflammation) in the myocardium.
Abstract 18826: Atrial Fibrillation, Atrial Myopathy, and the Risk of Recurrent Stroke or Transient Ischemic Attack After Cryptogenic Stroke
Authors: Joseph Raco, Ravi Shah, Michael Farbaniec, Ankit Maheshwari
Journal: Circulation (2023)

Background: The annual risk of recurrent stroke after cryptogenic stroke (CS) is estimated at 3-6%. Atrial myopathy, characterized by left atrial structural and electrophysiological remodeling, is associated with atrial fibrillation (AF) and stroke. Hypothesis: Atrial myopathy is associated with an increased risk of recurrent stroke or transient ischemic attack (rCVA) within one year. Methods: Patients with interpretable echocardiograms who received an implantable loop recorder for CS at a tertiary care medical center (2015-22) were included and followed for at least 1 year. Left atrial emptying fraction (LAEF) and reservoir strain (LARS) were calculated from two-dimensional transthoracic echocardiograms. Covariates including congestive heart failure, hypertension, age, diabetes, sex, stroke/transient ischemic attack, vascular disease, carotid artery stenosis, and rCVA were ascertained by review of hospital medical records. Incident AF post CS was obtained from review of loop recorder data. Odds ratios were calculated using logistic regression models. Two-sided student's T-test was used to compare means of continuous variables. Results: 159 patients (mean age 74.4 years, 52.1% female) were followed for at least one-year post CS. Patients with rCVA had significantly lower LAEF (p=0.012) and near-significantly lower LARS (p=0.088) compared to those who did not. The odds of rCVA were 4.82 (2.22, 7.11)-fold greater in those found to have new AF independent of LAEF, LARS, and remaining covariates including carotid artery stenosis. Patients on anticoagulation at time of rCVA had trends towards reduced stroke severity (p=0.184). Conclusions: Atrial myopathy characterized by AF or reduced LA function is associated with rCVA post CS.
Abstract 13915: Comparison of Proteomic CV Risk to Established ASCVD 10-year Risk Decision Points
Authors: Michael Hinterberg, Nelson P Trujillo, Rosalynn Gill, Clare Paterson, Jessica Chadwick, Missy Simpson, Jessica Kuzma, Stephen A Williams
Journal: Circulation (2023)

Introduction: The ASCVD pooled cohort equation (PCE) is well-established for CV risk assessment. Decision points for determining treatment plans are low, intermediate and high risk over 10 years, however this approach over and underestimates risk in certain subgroups. The validated CV Risk SomaSignal® Test (SST) provides 4-year risk probability of MACE allowing for timely assessment of risk, but the shorter timescale makes comparison to 10-year PCE risk less intuitive. Hypothesis: Using a previously described metacohort (n=5,575) of patients with increased CV risk, we hypothesized that PCE would stratify patients differently than the CV Risk SST, and that CV Risk score scaled to 10 years would yield an improved net reclassification index (NRI). Methods: CV Risk SST and PCE scores were calculated on metacohort plasma samples. CV risk score was scaled to 10 years by parameterizing the model for a 10-year score, and then calculating a quadratic equation for the conversion. CV risk score was stratified by four established risk bins, whereas the PCE was stratified similarly using &lt;7.5%, 7.5%-15%, 15%-20%, and &gt; 20% risks based on literature and practice-derived cutoffs. Event rates were compared between scores, and NRI was calculated. Results: We observed total NRI of 11.4% for the 10-year CV Risk SST vs. PCE, with up-classification (positive NRI=83.7%) mitigating down-classification (negative NRI=-0.723). Event rates for the high-risk group in the CV Risk test were higher than the PCE, and lower in the low-risk group (p &lt; 0.05). Conclusions: The CV Risk SST stratifies patients by identifying low- and high-risk groups using thresholds that are more discriminatory than low-risk and high-risk thresholds in the PCE. For comparison, the CV risk SST can be scaled to 10-year risk, with CV risk SST having a positive NRI for identifying MACE. This reclassification can allow targeted therapies in patients at greater risk and use of non-pharmacological therapies in the low-risk patients.
Abstract 13186: Factors Associated With Dysglycemia and Type 2 Diabetes Mellitus Onset in Familial Hypercholesterolemia
Authors: Flavia C Maia, Marcio H Miname, Kleisson A Maia, Ana P Chacra, Viviane Z Rocha, Marjorie Mizuta, Cinthia Elim Jannes, Jose E Krieger, Alexandre Pereira, Raul D Santos
Journal: Circulation (2023)

Introduction: Familial hypercholesterolemia (FH) is an autosomal dominant monogenic disorder characterized by high blood LDL-C and cardiovascular disease (CVD). Type 2 diabetes mellitus (T2DM) is an independent cause of CVD and there is evidence that FH is associated with a lower frequency of its development. On the other hand, lipid lowering therapy (LLT) may increase T2DM risk. Goals: Evaluate the risk of dysglycemia and T2DM development in a cohort of molecularly proven FH individuals. Methods: This is a prospective analysis of a population enrolled on a genetic cascade screening program evaluated from March 2011 to January 2022. FH diagnosis was confirmed by molecular testing of variants in LDLR, APOB and PCSK9. Dysglycemia and T2DM diagnoses were done according to the ADA Criteria or use of any antidiabetic drugs. Results: 790 FH patients were included (age 45.5±15.0 years, 56.8% female, baseline LDL-C 198±74 mg/dL), 96.6% had LDLR variants. The prevalence of T2DM was 13.3% and 67.4% were taking LLT at baseline . There were 206 (26%) new cases of T2DM or dysglycemia after a median 51-month follow-up . In multivariate Cox regression analysis age (HR:1.026, CI95%: 1.014-1.038, p=0.000) , body mass index (HR: 1.062, CI95%: 1.035-1.090, p=0.000) and current smoking (HR: 2.005, HR: 1.337-3.008, p=0.001) were independently associated with T2DM and dysglycemia, while metformin use was associated with a lower risk (HR: 0.147, CI95%: 0.076-0.284, p=0.000). History of previous CVD, use of lipid lowering therapy at baseline, high intensity LLT , or type of molecular defect were not associated with higher T2DM/dysglycemia risk. Conclusions: In this cohort of molecularly proven FH subjects, T2DM affected more than 1 in 10 people at baseline. Previous CVD and classical risk factors but neither molecular defects nor lipid lowering therapy were associated with T2DM/dysglycemia onset.