tbuckley/cabot-search huggingface dataset:
Abstract 14832: Comparative Effectiveness of Intravascular Ultrasound versus Angiography in Abdominal and Thoracic Endovascular Aortic Repair: Systematic Review and Meta-Analysis
Authors: Tomonari Shimoda, Mario D'Oria, Toshiki Kuno, Hisato Takagi, Patrick Heindel, Mohamad Hussain, Eric A Secemsky
Journal: Circulation (2023)

Introduction: The effectiveness of intravascular ultrasound (IVUS) with angiography compared with angiography guidance alone in the treatment of aortic conditions remains unclear. Objective: This systematic review and meta-analysis evaluates the evidence for IVUS use during thoracic (TEVAR) and abdominal (EVAR) endovascular aortic repair. Methods: A comprehensive search of MEDLINE, EMBASE, and Cochrane CENTRAL databases was conducted to identify studies comparing outcomes of patients undergoing TEVAR/EVAR with and without IVUS. The primary outcome was all-cause mortality during follow-up. Secondary outcomes included contrast volume, fluoroscopy time, perioperative mortality, and reinterventions during follow-up. Continuous variables, risk ratios (RRs), and hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from each study. Pooled analysis was performed using a random-effects model. Results: A total of 6,888 patients (n=4,226 IVUS and n=2,662 non-IVUS) from nine observational studies were included in the meta-analysis. The follow-up period ranged from 9 months to 25 months. The IVUS group exhibited a reduction in contrast agent volume (weighted mean difference (WMD) [95% CI] = -34.65 mL [-54.73, -14.57]) and fluoroscopy time (WMD [95% CI] = -6.13 min [-11.10, -1.15]) ( Figure 1A&amp;B ). Perioperative mortality was comparable between both groups (RR [95% CI] = 0.67 [0.40-1.12], respectively). Reintervention rates and all-cause mortality during the follow-up period were similar between the two groups (HR [95% CI] = 0.80 [0.33-1.97], HR [95% CI] = 0.75 [0.47-1.18], respectively) ( Figure 1C ). Conclusions: This systematic review and meta-analysis provides evidence that the use of IVUS enables safe and effective deployment of TEVAR and EVAR with reduced contrast agent usage and shorter fluoroscopy duration. These findings support the potential of IVUS as a valuable tool in endovascular aortic interventions.
Abstract 15722: Developing a Patient-Centered Roadmap to Reduce Maternal Morbidity/Mortality for Individuals With Congenital Heart Disease
Authors: Mindi Messmer, Scott Leezer, Ruth Phillippi, MARK ROEDER, Melissa Russo, Melissa Fries, Marc Cribbs, Anitha John
Journal: Circulation (2023)

Background: Individuals with congenital heart disease (CHD) face higher rates of pregnancy-related complications and interventions, however, few studies have assessed ways to improve outcomes. Goal: Improve reproductive care and reduce maternal morbidity and mortality for pregnant individuals with CHD. Methods: We formed a diverse consortium of CHD patients, providers, and advocates to identify knowledge deficits. Survey responses were solicited through social media and professional and advocacy networks. Results: As of 6/2/23, respondents included 815 (11% male, 88% female) patients from 48 states DC, and 216 providers (19% male, 81% female). Providers included 90 (42%) midwives, 59 (28%) adult congenital cardiologists, and 41 (19%) maternal-fetal medicine specialists. Most patient respondents are CHD patients (n=781, 96%) with complex CHD anatomy (n=606, 81%) between the ages of 30 and 44 (52%) with 72% reporting an annual household income over $75,000. Some patients reported they had received contraception counseling (n=262); counseling was provided by a physician (n=149, 57%), registered nurse (n=37, 14%), or parent (n=36, 14%). Of 189 CHD patients, the top reasons cited for not pursuing a pregnancy included not being ready (n=80, 42%), concerns about their heart condition (n=78, 41%), and physician advice due to potential complications (n=59, 31%). More than half of the patient respondents (n=231, 51%) reported a pregnancy, and 147 (64%) reported their pregnancy caused stress and anxiety. Cost and provider education are top priorities for improving care for pregnant individuals with CHD for respondents with household incomes under $49,000 per year while access to specialized heart care and obstetrics are top priorities for those with incomes over $50,000 (see Figure 1). Conclusions: CHD patients and providers are eager to provide their experiences relating to pregnancy and patient-centered research is an important tool to bridge the knowledge gap.
Abstract 13116: Profiling the Role of Gut Microbiota-Derived Trimethylamine- <i>N</i> -Oxide in Cardiac Fibrosis — Evidence From a Primary Human in vitro Model
Authors: Thomas A Agbaedeng, Sushma Rao, Marten Snel, Jean Jacques Noubiap
Journal: Circulation (2023)

Introduction: The gut derived trimethylamine- N -oxide (TMAO) is correlated with increased atrial inflammation and fibrosis and associated with atrial fibrillation, heart failure, and stroke. However, the mechanisms mediating these links remain unresolved. Hypothesis: TMAO and its precursor metabolite L-carnitine (LCART) induce the transformation of atrial fibroblasts into pro-fibrotic phenotypes. Aim: To characterise the association between TMAO and cardiac fibrosis. Methods: Primary human cardiac (atrial) fibroblasts (hCFs) were sourced from healthy donors. hCFs were starved for 24 h and treated with PBS (control), 20 ng/mL transforming growth factor beta 1 (TGFβ1), 10 mM TMAO, or 1.0 mM LCART for 72 h (n=6 in each), then analysed by flow cytometry for α-smooth muscle actin (αSMA) expression. Unbiased proteomics was performed using LC-MS/MS to determine protein expression profile. Results: Analysis of αSMA expression revealed 3 hCF states: quiescent (Fbs), quiescent-to-myofibroblast (intermediate [Fbs-myoFbs]), and fully activated myofibroblast (myoFbs), (Fig-A). Compared to controls, there was no difference in the intermediate state after TGFβ1, TMAO, or LCART treatment (p=0.30). TMAO and LCART resulted in a significant induction of myofibroblast states compared to controls and TGFβ1 group. Unbiased proteomics identified 92, 65, and 43 proteins to be overexpressed and 84, 46, and 78 proteins downregulated following TGFβ1, TMAO, and LCART treatments (Fig-B). Both TGFβ1 and TMAO demonstrated shared enrichment for oxidative stress-regulated ferroptosis pathway (fold enrichment [FE] 31.8 and 22.2, p &lt;.01 and 0.03); LCART showed enrichment for cell motility (FE 3.8, p=0.03). Conclusions: TMAO and its precursor L-carnitine are associated with activation of pro-fibrotic states, which may be due to oxidative stress and abnormal cell migration related mechanisms.
Abstract 16843: Diastolic Dysfunction Due to Structual Changes in Mutant Troponin I May Cause Restrictive Cardiomyopathy; Cryo-Electron Microscopic Analysis Using Induced Pluripotent Stem Cell Derived Cardiomyocytes
Authors: Moyu Hasegawa, Takuji Kawamura, Akima Harada, Emiko Ito, Maki Takeda, Masaki Taira, Takuji Watanabe, Yosuke Kugo, Daisuke Yoshioka, Kazuo Shimamura, Shigeru Miyagawa
Journal: Circulation (2023)

Introduction: Restrictive cardiomyopathy (RCM) is characterized by ventricular diastolic dysfunction with preserved contraction. Since there is no effective treatment other than heart transplantation, the development of novel treatment strategy by elucidating pathophysiology of RCM is an important issue under the serious donor shortage.Various troponin I mutations have been reported in patients with RCM and given that troponin I regulates the inhibition of cardiac contraction, it is possible that structural changes in mutant troponin I cause diastolic dysfunction in RCM. Recently, cryo-electron microscopy (cryo-EM) has made it possible to analyze the structure of thin filaments of muscle fibers. In this study, we applied the technology of induced pluripotent stem cell (iPSC) to cryo-EM structural analysis of thin filaments in cardiomyocytes from RCM patients with troponin I mutations. Methods: We established an iPSC line from a pediatric RCM patient with heterozygous TNNI3 mutation (R170W). Then the iPSCs were differentiated to cardiomyocytes to compare the cellular physiological, structural features. Normal adult iPS cell derived cardiomyocytes (Ctrl-iPSC-CM) were used as control. We also extracted thin filaments from iPSC-CMs and analyzed their structure with cryo-EM. Results: PCR analysis revealed the percentage of mutant alleles in TNNI3 mRNA was about 80% in the differentiated RCM-iPSC-CM, which was similar to the results in the myocardium of the same patient. The RCM-iPSC-CM demonstrated slower diastolic rate and longer diastolic time by cell motion analyses than Ctrl-iPSC-CM. Immunostaining showed a disarrayed sarcomeres in the RCM-iPSC-CM. Tthe structure of the thin filaments extracted from the RCM-iPSC-CMs observed with cryo-EM was close to that in the presence of calcium (contractile myocardium), even though the filaments were purified in the absence of calcium. Conclusions: The iPSC-derived cardiomyocytes could effectively represent the diastolic dysfunction of RCM. The structures of thin filaments were possibly explained for the phenotype of restrictive cardiomyopathy.
Abstract 17504: Revisiting the Etiology of a Non-Ischemic Cardiomyopathy
Authors: Alexandra B Steverson, Masataka Kawana
Journal: Circulation (2023)

Introduction: In the era of REVIVED-BCIS2 and ISCHEMIA clinical trials, the role of routine invasive coronary angiography for treatment of coronary artery disease (CAD) in the setting of left ventricular dysfunction has come into question. While the majority of heart failure (HF) patients undergo some form of non-invasive ischemic evaluation, there are a wide range of opinions on which testing modality is the most appropriate. Case: This is a 53 year-old man with a history of HTN, HLD, and presumed non-ischemic cardiomyopathy and LVEF of 15-20%, first diagnosed in 2009. He had a family hx of heart disease in several distant relatives, thus the etiology was presumed familial. In 2022, he had NYHA class II symptoms and a routine echo showed a LVEF of 25% with anteroseptal hypokinesis. Given these findings, a coronary CTA was obtained. This demonstrated infarct in the LAD territory and a proximal left main to mid-LAD aneurysm measuring up to 7 mm with a partially calcified shell and peripheral thrombus, consistent with prior Kawasaki’s disease (KD). He was initiated on a DOAC to prevent further embolic events and aspirin. He is now undergoing serial monitoring of the aneurysm size, thrombus burden, and functional testing to monitor for ischemia. Discussion: Non-invasive anatomic testing to evaluate for CAD in HF patients can provide useful information over a functional assessment. KD is a rare disease with an estimated incidence rate of ≈25 per 100,000 children less than 5 years of age. KD can lead to coronary artery aneurysms, which often contain thrombi, and subacute/chronic myocarditis. The affected arteries can become stenotic over time or even occlude, leading to ischemic injury later in life. Early recognition of this rare disease is important to initiate appropriate treatment and prevent thromboembolic complications. Conclusion: KD is a rare cause of adult cardiomyopathy. Anatomic testing was essential to appropriately diagnose and treat this patient’s cardiomyopathy.
Abstract 14658: Echocardiographic Metrics Before Coronary Artery Bypass Grafting Are Associated With Postoperative Kidney Injury in Patients With Preserved Ejection Fraction, and Mean Perfusion Pressure May Mediate This Relationship
Authors: Natalie Waldron, Virginia S Hahn, Joao AC Lima, Lee Goeddel
Journal: Circulation (2023)

Introduction: Preserved left ventricular ejection fraction (LVEF) patients often suffer acute kidney injury (AKI) after coronary-artery bypass surgery (CABG). We studied the relationship of relative wall thickness (RWT) and LV filling pressure (E/e’), measured by preoperative transthoracic echocardiogram (TTE), with AKI in this population. As these markers may identify subclinical cardiac dysfunction, we also examined the role of intraoperative hypotension by mean perfusion pressure (MPP). Hypothesis: Are LV RWT and E/e’ from preoperative TTE associated with post-CABG AKI in preserved LVEF patients? Are LV RWT and E/e’ associated with hemodynamic instability measured by total minutes of MPP (MAP-CVP) &lt; 60mmHg (1 min. resolution)? Aims: We aim to identify novel preoperative TTE markers that provide mechanistic insight (low MPP) to AKI development in preserved LVEF patients undergoing CABG. This could lead to interventions during high-risk surgeries to reduce AKI. Methods: We accessed 1343 patient records and used multivariate logistic regression models adjusted for covariates (Fig. 1). Results: Mean (SD) age was 65 (10). 170/709 patients had AKI. RWT and E/e' are weakly correlated (r=.15, p=.0075, n=314). Each E/e’ increase associated with AKI, OR 1.11 (1.04-1.19, p=.003). Every 0.1 RWT increase associated with AKI, OR 1.21 (1.02-1.43, p=.031, n=518). Each minute MPP &lt; 60mmHg associated with 0.6% AKI increase (n=714). E/e’ associated with low MPP; RWT did not. Conclusion: In preserved LVEF patients, RWT and E/e’ are associated with higher AKI risk after CABG. E/e’ is also associated with intraoperative MPP&lt;60mmHg, which may partially mediate the E/e’-AKI relationship.
Abstract 13909: It’s All About the Fat: Most Subjects With Metabolically Obese Normal Weight Have Either High Body Fat or Central Obesity
Authors: zhuo chen, Jingen Li, Betsy Medina-Inojosa, Jose R Medina-Inojosa, Kyla Lara-Breitinger, Virend K Somers, Andres Acosta, Amir Lerman, Francisco Lopez-Jimenez
Journal: Circulation (2023)

Introduction: Metabolically obese normal weight (MONW) refers to metabolic abnormalities despite normal body mass index (BMI). Hypothesis: Because obesity is generally defined by BMI, it is assumed that people with MONW do not have excessive adiposity but still have the metabolic dysregulation associated with adiposity. Methods: We included participants aged 20-65 of the National Health and Nutrition Examination Surveys from 1999-2006 and 2011-2018 with normal BMI (18.5-25 kg/m 2 ), fasting blood samples, and DEXA data. According to the AHA criteria, MONW was defined having ≥3 of the following criteria, besides a normal BMI: Hypertriglyceridemia (≥ 150 mg/dL) or treatment for elevated triglycerides; HDL cholesterol level &lt; 40 mg/dL in men or &lt;50 mg/dL in women or treatment for reduced HDL-C; elevated blood pressure (systolic ≥ 130 mmHg and/or diastolic ≥ 85 mmHg) or antihypertensive treatment or history of hypertension; elevated fasting plasma glucose ≥ 100 mg/dL or insulin/oral hypoglycemic treatment and central obesity by waist circumference (≥ 94 cm in men and ≥ 80 cm in women). High fat percentage was defined as ≥25% in men, ≥35% in women. Weighted logistic regression was performed to test the relation between MONW and high fat%, central obesity. Results: Of the 7,887 participants (53.6% men; mean age±SE was 39.23±0.24 years), 2433 (33.4%) had normal BMI included in the analysis. Among these, 148 had MONW (5%). Mean Fat% was 26.08±0.36% in those with MONW versus 21.90±0.17% in those without MONW for men, and 37.02±0.35% versus 33.31±0.21% for women. MONW subjects were 2.21 times more likely to have either central obesity or high fat % (OR 12.09, 95%CI: 6.18-23.67, p&lt;0.01) and 2.18 times more likely to have high fat % (OR=2.84, 95%CI: 1.72-4.67, p&lt;0.01) (see Figure). Conclusions: Most individuals with MONW have either increased fat content, central deposition of fat, or both. That highlights people with normal BMI may still have metabolic complications of adiposity.
Abstract 14676: Susceptibility to Cardiac-Targeted Irradiation in Wild-Type and Nos1 Haploinsufficient Mice
Authors: Jason M Dierdorff, Haider Mehdi, Mohamed Elmonzer, Alexander Greiner, Kyle Current, Jin-Young Yoon, Sruti Prathivadhi-Bhayankaram, Gina Morgan, William J Kutschke, Peter Wipf, Michael Epperly, Bryan G Allen, Douglas R Spitz, Joel Greenberger, Barry London
Journal: Circulation (2023)

Introduction: Cardiac irradiation causes heart failure and arrhythmias. We reported that cardiac-targeted irradiation (CTI) led to cardiac dilation with increased end diastolic volume (EDV) by echocardiogram (echo) after 9 months in wild-type C57Bl6/J (WT) male (M) but not female (F) mice. Both sexes developed cardiac fibrosis and evidence of lung congestion, and the radiation mitigator MMS350 did not protect either sex. Here, we studied the effect of CTI on Nitric Oxide Synthase 1 haploinsufficient (Nos +/- ) mice treated with/without MMS350. Methods: 10 week-old Nos +/- and WT mice were exposed to 20 Gy CTI (R) with or without MMS350 (D) and followed for 9 months (Nos +/- : +R+D, n = 9M, 6F; +R-D, n = 6M, 7F; WT: +R+D, n = 12M, 14F; +R-D, n = 13M, 14F), with parallel unirradiated controls (Nos +/- : -R+D, n = 8M, 6F; -R-D, n = 10M, 7F; WT: -R+D, n = 8M, 12F; -R-D, n = 7M, 8F)). Echos and EKGs were performed at baseline and every 3 months. Heart weight (HW), lung weight (LW), and body weight (BW) were measured. Results: Unlike irradiated male WT mice where EDV was increased (p=0.001), EDV was smaller in male (p=0.04) and EF was decreased in both male (p=0.01) and female (p=0.05) Nos +/- irradiated mice compared to unirradiated controls, independent of MMS350 treatment (Figure). In addition, the PR interval was shorter in irradiated Nos +/- male (p=0.008) and female (p=0.003) mice compared to unirradiated controls. HW/BW was not significantly changed in any group, while LW/BW was significantly increased only in WT male (p=0.04) and female (p=0.001) irradiated mice. Conclusions: In long term follow-up of CTI-treated mice, Nos1 deficiency prevents sex-specific cardiac dilation in males, promotes left ventricular systolic dysfunction and alters cardiac conduction system properties. Further investigation into the role of nitric oxide in radiation-induced cardiac damage and the mechanisms underlying sex differences in the response to radiation are warranted.
Abstract 18445: Rigorous Mechanics in Engineered Heart Tissues
Authors: Benjamin W Lee, Jamie Moni, NESRINE BOUHRIRA, Alisa N DeGrave, Noah R Boone, Elise A Corbin, Kenneth B Margulies
Journal: Circulation (2023)

Introduction: Heart failure can develop or be exacerbated by mechanical stressors, including increased diastolic strain (preload) and increased systolic impedance (afterload). Recent advances in human induced pluripotent stem cell (iPSC) technology and tissue engineering have enabled long term culture and maturation of engineered heart tissues (EHTs). Most current platforms do not allow for mechanical assessment under a range of loading conditions. Here, we develop a technique to engineer cardiac tissues that allow for non-destructive rigorous phenotyping of tissue mechanics. Methods: Custom tissue anchors were 3D printed using Boston Micro Fabrication HTL Resin and placed within polydimethylsiloxane tissue casting molds. iPS cardiomyocytes and ventricular fibroblasts were mixed 5:1 in 2 mg/mL collagen and cast in rectangular molds. Tissues were compacted around custom tissue anchors over 14 days. Tissues were dismounted from the molds and fixed for immunostaining or hooked onto a force transducer for length-tension, force-frequency, and work-loop analysis. Results: 3D printed tissue anchors accommodated EHT molding and compaction. EHTs spontaneously contracted after 3 days in culture, and compacted to 15.9±0.8% their initial tissue area by 14 days of culture. Engineered tissues were cell dense and mature, with bands of aligned sarcomeres. During isometric testing, tissues display a physiologic length-tension relationship, with linear increases in force with stretch between L 0 (slack length) and L max (length at maximum active force generation, 4.3±0.7 mN/mm 2 ; r 2 =0.96). These are coupled with increases in contraction and relaxation velocities. EHTs were capable of mimicking physiologic work loops. Conclusions: In summary, we have shown the ability to grow and mature three-dimensional human engineered heart tissues capable of rigorous mechanical assessment, enabling future studies on load-dependent cardiac remodeling.
Abstract 16722: Performance Evaluation of ChatGPT 4.0 on Cardiovascular Clinical Cases From the USMLE Step 2CK and Step 3 of the National Board of Medical Examiners
Authors: Joseph Kassab, Christopher Massad, Vishwum Kapadia, Abdel Hadi El Hajjar, Joseph El Dahdah, Michel Chedid El Helou, Elio Haroun, Jay Ramchand, Serge C Harb
Journal: Circulation (2023)

Introduction: As the prominence of online chat-based artificial intelligence (AI) platforms increases, medical students and residents in training may be inclined to utilize these tools as supplementary resources while preparing for their United States Medical Licensing Board (USMLE) examinations. Hypothesis: The aim of this study was to assess the performance of ChatGPT 4.0 in responding to cardiovascular (CV) clinical vignettes from USMLE sample questions provided by the National Board of Medical Examiners (NBME). Methods: We extracted the 31 CV clinical vignettes from the official NBME USMLE Step 2 Clinical Knowledge and Step 3 self-assessments, and submitted them to ChatGPT 4.0. The clinical cases encompassed a range of topics such as preventive medicine, congenital heart disease, valvular heart disease, electrophysiology, heart failure, and pericardial disease. Each of the 31 cases had a MCQ: 29/31 had at least 5 answer choices, while the remaining 2 had 4 answer choices each. The performance of the AI model was assessed using the NBME-provided answers. Subsequently, two experienced cardiologists independently reviewed the explanations provided by the model for each case and classified them as “accurate” - if they aligned with appropriate guidelines, and as “inaccurate” if they conveyed incorrect or inappropriate information. Results: The AI model attained a grade of 90.3% (28/31). The initial agreement between the 2 reviewers was near perfect with a Cohen’s Kappa of 0.85. Any identified discrepancies were subsequently addressed and resolved. Of the correctly answered questions, accurate explanations were provided by the AI model in 89.2% of cases (25/28). Conclusions: The high performance of ChatGPT 4.0, suggests it could be an effective additional CV study resource for residents and medical students preparing for the USMLE Step 2 CK and Step 3 exams.