tbuckley/cabot-search huggingface dataset:
Abstract 4139728: Aortic Arch Calcification Among Cigarette Smokers: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Salman Ansari, Robert Trujillo, Robyn McClelland, Matthew Budoff
Journal: Circulation (2024)

Background and Aims: Cigarette smoking is a known contributor to cardiovascular disease (CVD) and is associated with increased prevalence of coronary artery calcium. However, despite this clinical significance, calcium deposition in other vascular beds, specifically the aortic arch, has yet to be thoroughly investigated among cigarette smokers. Methods: The study population comprised 3026 participants who underwent non-contrast chest CT scans in MESA exam 5. Aortic arch calcium (AAC) is defined as calcification in the transverse aortic arch, as measured using the Agatston method on chest CT scans. Log-transformed AAC scores were used for all analyses. Multivariate linear regression models were fit to assess the relationship between log-AAC and cigarette smoking status (never-smoked, former smoker, current smoker). Cox proportional hazard models were fit to investigate the relationship between log-AAC and incident CVD and mortality for those with a history of smoking (former&amp;current smokers). All models were adjusted for demographic and traditional clinical risk factors. Results: After excluding those with missing variables, 2196 participants were included in the final analysis, of which 1119 self-identified as never smokers, 901 as former smokers, and 176 as current smokers. Estimated mean log-AAC was 0.557 (p&lt;0.001) log-Agatston units higher in former smokers compared with never smokers [95% CI: 0.374 - 0.741], and 1.030 (p&lt;0.001) log-Agatston units higher in current smokers compared with never smokers [95% CI: 0.703 - 1.358]. Among ever-smokers (current or former smokers), a one log-Agatston unit increase in log-AAC was associated with a 20.6% (p = 0.002) increased risk for CVD events [95% CI: 7.4% - 35.5%] and a 12% (p = 0.020) increased risk for mortality [95% CI: 2% - 23%]. Conclusion: This study demonstrated a potential association between cigarette smoking and AAC scores, with significant differences in AAC among current, former, and never smokers. Furthermore, AAC is associated with incident cardiovascular events and mortality among those with a history of smoking.
Abstract 4139834: Pulse Pressure in Heart Failure with Mildly Reduced or Preserved Ejection Fraction: A Pooled Participant-Level Analysis of 4 Large-Scale Trials
Authors: Henri Lu, Toru Kondo, Brian Claggett, Muthiah Vaduganathan, Brendon Neuen, Iris Beldhuis, Pardeep Jhund, Finnian Mc Causland, Inder Anand, Marc Pfeffer, Bertram Pitt, Faiez Zannad, Michael Zile, John McMurray, Scott Solomon, Akshay Desai
Journal: Circulation (2024)

Background: Pulse pressure (PP), a marker of aortic stiffness, is associated with risk for mortality and cardiovascular (CV) events, but these associations have not been extensively explored in patients with heart failure (HF). We examined the association between PP and CV outcomes in a pooled dataset of 4 large, well-characterized cohorts of patients with HF with moderately reduced (mrEF) or preserved EF (pEF). Methods: I-PRESERVE, TOPCAT, PARAGON-HF and DELIVER were global, multicenter, randomized clinical trials testing irbesartan, spironolactone, sacubitril/valsartan and dapagliflozin respectively, against either a placebo or an active control (valsartan in PARAGON-HF), in patients with HF and a LVEF &gt;40% (in DELIVER) or ≥45% (in the other trials). Predictors of higher PP were identified using forward stepwise regression analysis. The relationship between baseline continuous PP and the incidence rates (IR) of first HF hospitalization (HFH) or CV death was analyzed with restricted cubic splines. To assess the prognostic significance of incorporating systolic blood pressure (SBP) along with PP, we categorized patients into 4 groups based on median values of PP and SBP. Results: A total of 18,627 patients (age 71±9 years, 49% men, PP 55±14 mmHg, SBP 131±15 mmHg) were included. Over a median follow-up of 2.9 years, 3,852 patients experienced a first HFH or CV death event (7.4 events per 100py). Predictors of higher PP values included higher SBP, older age, female sex, Asian race, higher EF, use of diuretics, higher N-terminal pro B-type natriuretic peptide (NT-proBNP) levels, and diabetes. Conversely, factors associated with lower PP included atrial fibrillation, higher heart rate, worse New York Heart Association (NYHA) Functional Class, use of beta-blockers, and higher estimated glomerular filtration rate. After adjusting for predictors of PP and other relevant variables, higher PP was associated with a higher risk for HFH or CV death. This relationship was nonlinear (p&lt;0.001), with risk increasing markedly at higher PP values ( Figure 1 ). After multivariable adjustment, higher PP was associated with higher CV risk regardless of baseline SBP, compared to lower PP and lower SBP ( Figure 2 ). Conclusions: Our analysis of a pooled dataset from 4 clinical trials including patients with HFmrEF or pEF suggests that PP was an independent predictor of CV events in this population, regardless of baseline SBP.
Abstract 4139874: Contemporary Trends in New-onset Atrial Fibrillation after Transcatheter Aortic Valve Implantation and Surgical Aortic Valve Replacement
Authors: Dhan Shrestha, Sajog Kansakar, Jurgen Shtembari, Monodeep Biswas, Ghanshyam Shantha, James Storey, Daniel Katz
Journal: Circulation (2024)

Background: New-onset atrial fibrillation (AF) frequently occurs after cardiac procedures, such as transcatheter aortic valve replacement (TAVI) and surgical aortic valve replacement (SAVR), and is linked with significant morbidity and mortality. In the context of improving TAVI technology and physician expertise, we investigated the recent trends in procedure volume, in-hospital mortality, and atrial fibrillation associated with TAVI and SAVR. Method: We conducted a retrospective study using the National Inpatient Sample (NIS) data from 2016 to 2020. We identified all TAVI and SAVR admissions using ICD-10 codes and compared the temporal trends in procedure volume, in-hospital mortality, and AF. Results: A total of 296,275 TAVI and 298,300 SAVR were performed between 2016-2020. There was an increase in the annual volume of TAVI performed from 40,005 to 75,740 (p trend &lt;0.01), along with a decrease in in-hospital mortality (1.85% to 1.19%, p trend &lt;0.01) and new-onset AF (39.5% to 23.5%, p trend &lt;0.01), this could be due to broadening of TAVI indications. For SAVR, there was a decrease in annual procedural volume (70,895 to 46,090, p trend &lt;0.01) and associated new-onset AF (45.3% to 37.0%, p&lt;0.01), but an increasing trend in in-hospital mortality (3.31% to 4.04%, p trend=0.03). AF was associated with 51% of TAVI and 77% of SAVR admissions. The predictors of AF included age, female sex, white race, chronic kidney disease, chronic lung disease, heart failure, coronary artery disease, diabetes mellitus, hypertension, chronic liver disease, obesity, smoking, and coagulopathy. In multivariate analysis, AF was not solely associated with in-hospital mortality after SAVR (aOR 0.78, 95% CI 0.65-0.79, p&lt;0.01) or TAVI (aOR 1.1, 95% CI 0.94-1.29, p=0.24). Conclusion: In this real-world study using contemporary data from NIS, we observed that annual TAVI numbers are increasing compared to SAVR, and associated AF and in-hospital mortality is decreasing. This is likely due to improved TAVI valves, techniques, and expertise in the field, as well as broadening TAVI indications to a relatively healthier AS patient population. In our analysis, AF did not predict in-hospital mortality for TAVI or SAVR.
Abstract 4139716: Acetylation of Electron Transfer Flavoprotein Alpha Is a Possible Regulatory Mechanism of Fatty Acid Oxidation in Diabetic Hearts
Authors: Yuki Tatekoshi, Masaki Yano, Ryusuke Hosoda, Yukika Saga, Atsushi Kuno
Journal: Circulation (2024)

Background: Augmented fatty acid oxidation (FAO) adversely affects cardiac function in diabetic patients. Mitochondrial protein lysine (K) acetylation is a critical mechanism modifying metabolic flux, yet specific acetylation targets enhancing FAO are unknown. Purpose: This study aimed to identify proteins whose acetylation increases FAO activity in diabetic hearts using multi-omics analyses. Methods: We used Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats, a type 2 diabetes model aged 32-38 weeks, which display early-stage cardiomyopathy, and Long-Evans-Tokushima-Otsuka (LETO) rats as controls. Metabolomics, acetylomics, and proteomics were performed on samples from these hearts. Results: OLETF had elevated blood glucose (194.0 vs 137.9 mg/dL, P = 0.0022) and Myh7 mRNA expression (7.11 vs 4.41 units, P = 0.0063) compared to LETO, indicating diabetes and cardiac dysfunction. Metabolomics revealed a decreased fumarate/succinate ratio in OLETF (0.51 vs 0.99 units, P = 0.0083), indicating suppressed activities of TCA cycle and complex II in the electron transport chain (ETC). FAO provides reducing equivalents through acetyl-CoA supply into TCA cycle and directly to ubiquinone via electron transfer flavoprotein (ETF), highlighting ETF's role in FAO upregulation in diabetic hearts. Acetylomics in mitochondrial fractions identified 55 acetylated K residues on 24 mitochondrial proteins increased by 1.5-fold (P &lt; 0.05) in OLETF compared to LETO, with these proteins enriched in the FAO pathway. Specifically, K69-Ac, K75-Ac, and K126-Ac on ETFA, a subunit of ETF, were detected. To determine whether increased acetylation or protein expression contributed to the acetylomics signals, proteomics was performed on identical samples. Of 24 proteins, 22 were measurable, with several critical FAO-related proteins (e.g., ACADVL, ACADM, HADHA, HADHB, ACOT2) significantly more expressed in OLETF than in LETO, while ETFA expression remained similar (1.01 vs 1.00 units, P = 0.84). This suggests increased acetylation signals in FAO-related proteins are mainly due to upregulated protein expression, except for ETFA. Conclusions: While increased expression is commonly seen in FAO genes in diabetic hearts, protein acetylation of ETFA appears to be a crucial compensatory mechanism to transfer reducing equivalent to ETC from the FAO under the reduced TCA cycle activity. These findings provide insights into the mechanisms underlying metabolic disturbance in the early stage of cardiomyopathy.
Abstract 4139704: Coronary Artery Air Embolism During Left Heart Catheterization: A Rare Yet Potentially Fatal Complication
Authors: Arsalan Siddiqui, Brianna Yee, Michael DiCaro, Ki Lee, KaChon Lei, Chowdhury Ahsan
Journal: Circulation (2024)

Coronary artery air embolism is a rare yet potentially fatal complication of interventional cardiac procedures, presenting from asymptomatic to cardiac arrest. There are no established guidelines for its management, and the focus is on primary prevention. Here, we present a case of iatrogenic coronary artery air embolism during an elective left heart catheterization (LHC). A 61-year-old male with mitral valve prolapse underwent preoperative LHC which showed a stenotic left anterior descending artery and normal right coronary artery (RCA). On the following left ventriculogram, significant inferior wall hypokinesis was observed, and the patient developed acute chest pain, ST elevations, and complete heart block (Figure 1a). Suspecting new RCA pathology, reevaluation revealed multiple air emboli and Thrombolysis In Myocardial Infarction (TIMI) grade 1 flow (Figure 1b). The RCA was flushed multiple times with heparinized saline, resolving the air emboli and restoring TIMI grade 3 flow (Figure 1c). At the procedure's end, the patient was pain-free and in sinus rhythm. A repeat transthoracic echocardiogram showed normal ventricular function without regional wall motion abnormalities. The patient was discharged without further complications. Coronary air embolism can occur iatrogenically and is inversely correlated with operator experience. Prevention through proper technique is crucial: catheters should be adequately aspirated, all connections tightened, and the catheter should be tested distal to the aortic cusp to prevent emboli occurrence. Although there are no established guidelines, management includes administering 100% oxygen, intracoronary saline boluses, or breaking down emboli with a guidewire. In our case, the sudden onset hypokinesis of the inferior wall with complete heart block in a confirmed normal RCA raised suspicion for new RCA pathology. Immediate heparinized saline allowed for air emboli dissociation as a more immediate intervention than 100% oxygen and did not involve intravascular manipulation which could result in dissection. Our case highlights the importance of early detection of rapidly changing pathology and stresses meticulous technique for testing equipment as a prevention method.
Abstract 4139672: 12,13-diHOME Attenuates Pro-Arrhythmic Effect of High-Fat Diet
Authors: Benjamin Buck, Natalia Areiza, Xianyao xu, Austin Elliott, Xiaoping Wan, Drew Nassal, Cemantha Lane, Shinsuke Nirengi, Natasha Maria James, Lisa Baer, Isabelle Deschenes, Krishna Chinthalapudi, Daniel Gallego-Perez, Kristin Stanford, Thomas Hund
Journal: Circulation (2024)

Introduction: Obesity is a risk factor for atrial fibrillation (AF) and its incidence that has tripled over the past 30 years. Obesity is associated with dramatic changes in atrial structure and electrophysiology through unclear mechanisms. The linoleic acid metabolite 12,13-dihydroxy-9Z-octadecenoic acid (12,13-diHOME) is a signaling lipid released by brown adipose tissue that acts in an endocrine manner on myriad tissues including the heart. 12,13-diHOME enhances cardiac myocyte Ca 2+ cycling and overall function, though the precise mechanisms are undetermined. This study tested the hypothesis that 12,13-diHOME inhibits the pro-arrhythmic molecule Ca 2+ /calmodulin-dependent kinase II (CaMKII). We propose that obesity-induced loss of 12,13-diHOME promotes CaMKII dysfunction, in vitro ectopy and atrial arrhythmia (AA). Methods: Adult male and female mice were fed either high fat diet (HFD, 60% kcal from fat) or normal chow (NFD) (21% kcal from fat) for 8-16 weeks. Atrial myocytes were isolated for action potential (AP) measurements using whole-cell patch clamp ±12,13-diHOME (5 μM). To test the effect of 12,13-diHOME on AA inducibility, a second cohort of mice was fed HFD and subjected to weekly tissue nanotransfection for non-viral delivery of either Ephx1/2 (HFD-TNT), enzymes responsible for production of 12,13-diHOME, or empty plasmid (HFD-con). Following treatment, mice underwent intracardiac pacing studies to determine AA inducibility. The ability of 12,13-diHOME to directly interact with and inhibit CaMKII was tested using purified components with in vitro radioassay and microscale thermophoresis. Results: HFD induced atrial myocyte AP duration prolongation and a higher incidence of spontaneous depolarization compared to NFD, both of which were reversed by 12,13-diHOME (figure). HFD-TNT exhibited decreased phospho-CaMKII compared to HFD-con mice. In parallel, HFD-TNT trended toward reduced inducibility of AA (0/7 mice inducible, 0%) compared to TNT-CON mice (5/7, 58%) (p=0.07). Radioassay revealed that 12,13-diHOME inhibits CaMKII; thermophoresis demonstrated direct binding with K 1/2 = 19 mM. Conclusion: HFD induces dysregulation in 12,13-diHOME and CaMKII signaling together with defects in atrial myocyte excitability and AA in mice. Non-viral overexpression of 12,13-diHOME shows promise in normalizing CaMKII activity and reducing AA burden. 12,13-diHOME represents a novel avenue for direct regulation of CaMKII signaling and downstream pathology in the heart.
Abstract 4139594: Temporal Evolution and Incidence of Device Related Thrombus in Left Atrial Appendage Closure
Authors: Alisha Alabre, Salvatore Savona, John Hummel, Muhammad Rizwan Afzal
Journal: Circulation (2024)

Background: Studies related to the Watchman device generally report data at the 45-day, 6-month, 1-year, and 2-year intervals, with outcomes supportive of Watchman closure. The imaging of the device at 45 days is believed to coincide with substantial completion of device endothelization and the end of the high risk period for device related thrombus (DRT). Thus, prophylactic systemic anticoagulation (SA) is often discontinued at this time. Objective: To report the incidence of delayed DRT in patients following the 45 day post-implant imaging and the cessation of SA. Methods: In this single center retrospective study, we assessed patients undergoing Watchman device placement between April 16, 2016, and June 30, 2022. Patient data was retrieved from our institutional Cardiovascular Data Registry database. Following Watchman device implantation, all patients underwent a 45-day surveillance TEE or CT. Our primary interest was assessing the incidence and timing of delayed DRT and determining the anti-platelet and/or SA regimen at the time of DRT. Results: A total of 861 patients who underwent Watchman device placement were included in the study. The 45-day surveillance imaging revealed that 2.2% (19/861) of patients exhibited a DRT during the initial follow up imaging while on SA and aspirin (ASA). These patients continued on SA/ASA until the 6-month imaging, at which point 84% (16/19) patients showed DRT resolution. Among the 2 with persistent thrombus, one was on ASA/warfarin, while the other was on DAPT. The 3rd patient did not complete subsequent imaging after 45 days. The patients without DRT at 45-day imaging had a 0.83% (7/842) incidence of DRT with 42.9% (3/7) revealed at 6 month, 42.9% (3/7) revealed at 12 months and the remaining 14.3% (1/7) at 24 month imaging. SAPT/SA protection was in place in 57.1% (4/7) of these cases, while the remainder were on SAPT 28.5% (2/7), or nothing at all 14.3% (1/7). Alarmingly, 2/7 of these cases resulted in an ischemic stroke in the absence of SA. In 85% of cases, DRT was associated with peridevice leak. Conclusion: These findings underscore the importance of ongoing surveillance in patients with Watchman devices and do not suggest a clear association between continued anticoagulation therapy and reduced risk of delayed DRT formation. Further investigations are warranted to determine whether there are predictive patient or implant characteristics and elucidate optimal management strategies for this patient population.
Abstract 4139637: Artificial Intelligence ECG Mapping of Biventricular Pacing QRS Morphology Predicts Response to Cardiac Resynchronization Therapy
Authors: Kendall Oliver, Stephanie Hull, Mariana Velasquez, Peter Hall, Gordon Ho, Frederick Han, Kurt Hoffmayer, Jonathan Hsu, Farshad Raissi, Gregory Feld, Andrew McCulloch, Indrajit Choudhuri, Christopher Villongco, Ulrika Birgersdotter-Green, David Krummen
Journal: Circulation (2024)

Background: Cardiac resynchronization therapy (CRT) is an important treatment modality for patients with heart failure and electrical dyssynchrony. A current limitation is that approximately 30% of patients do not respond, and identification of patients at greater risk for suboptimal outcome remains challenging. Hypothesis: We hypothesized that an artificial intelligence (AI) ECG mapping system would identify maladaptive ECG activation patterns in non-responders to CRT-defibrillator (CRT-D) therapy. Aims: We endeavored to analyze the biventricular-paced 12-lead ECG QRS complex using a novel AI tool and compare the projected segment of origin between responders and non-responders. Methods: We enrolled patients with heart failure 6 months or more after CRT-D implantation. ECG samples obtained during routine clinical follow-up during LV, RV, and BiV pacing were analyzed with an AI-based ECG mapping system. The projected segments of origin for each pacing setting were noted using a validated 30 segment ventricular model. CRT responders were defined as ≥5% increase in LVEF at 6 to 12 months post-implantation. Results: Of 49 study patients, 35 were responders (age 74±9 y, LVEF 28±9%, 31% female) and 14 were non-responders (age 68±12 y, LVEF 32±5%, 20% female). LVEF increased in responders by 15±7% and decreased in non-responders by 3±5% (p&lt;0.001). Biventricular-paced ventricular activation patterns were significantly different between responders and non-responders: in non-responders, 8 of 14 patients (57.1%) had an activation pattern identified as mid to apical anterior or anteroseptal (Figure A) versus 6 of 35 responders (Figure B, 17.1%, p= 0.012). Left ventricular and right ventricular activation mapping results were not predictive. Conclusions: A maladaptive biventricular-paced electrical activation pattern, localized to the mid- or apical anteroseptal region of the LV, is associated with non-response to CRT. Studies of intraprocedural noninvasive LV activation mapping to improve target LV pacing site selection and response to CRT are underway.
Abstract 4139552: High-dimensional single-cell antibody-sequencing (AbSeq) analysis reveals age-associated myeloid cell subsets in coronary artery disease
Authors: Ravi Komaravolu, Nandini Chatterjee, Christopher Durant, Runpei Wu, Chantel McSkimming, Fabrizio Drago, Angela Taylor, Coleen McNamara, Yury Miller, Klaus Ley, Ahmad Alimadadi, Catherine Hedrick
Journal: Circulation (2024)

Introduction: Aging is strongly associated with increased vascular inflammation, particularly in individuals over 65. Given that the development of coronary artery disease (CAD) is positively correlated with age-related inflammation, the precise distribution of myeloid subsets across different ages and CAD severity remains unclear. Objective: To investigate the influence of aging on myeloid heterogeneity using peripheral blood samples from the Coronary Assessment in Virginia (CAVA) cohort. Methods: PBMC samples from CAVA subjects (older ≥65, younger ≤64) were analyzed using AbSeq-based high-dimensional analysis. The Gensini score assessed CAD severity (high_CAD &gt;32, low_CAD ≤ 6). Our analysis included 61 subjects in total, 33 older (18 high_CAD) and 28 younger (14 high_CAD). We examined age-wise associations across myeloid subsets. Results: We identified six major myeloid clusters: classical monocytes (cMo), intermediate monocytes (iMo), non-classical monocytes (nMo), plasmacytoid dendritic cells (pDC), conventional dendritic cells (cDC), and DC3. In all major clusters identified, the proportion of cMos (&gt;75%) was consistently higher across all age groups. Although no significant differences were noted in frequencies of major myeloid populations with age, further analysis revealed significant age-related changes in subclusters. A notable decrease was observed in the cMo_CD33 hi CD9 hi (p=0.043) subsets in older individuals. Ingenuity Pathway Analysis of genes associated with this cluster indicated activation of IL-4, and IL-13 signaling pathways. In older subjects with high_CAD, significant decreases were identified in two specific CXCR3 + subsets, cMo_CD14 lo CD33 lo CXCR3 + (p=0.0001) and cMo_CCR6 + CXCR3 + (p=0.006) compared to those with low_CAD. Gensini correlation analysis in the older population also revealed a significant negative association with two cMo_CXCR3 + subsets. Within myeloid-specific genes in the older population, positive correlations with Gensini scores were observed for Ctsa, Flt3, Ncf1, Cd38, and C1Qb . Conversely, Nr4a1 , Cxcl1, Cxcl2, Cxcl8 , Cd83 , and Dusp2 showed negative correlations. We observed an increase in cMo_TLR4 lo (p=0.02) and a decrease in cMo_CD33 hi CD9 hi (p=0.006) in younger populations with high_CAD compared to low_CAD. Conclusion: Our finding highlights age-related changes in myeloid populations and their association with increased cardiovascular risk, suggesting potential targets for therapeutic intervention.