tbuckley/cabot-search huggingface dataset:
Abstract 4135353: Accuracy, Hallucinations, and Misgeneralizations of Large Language Models in Reviewing Cardiology Literature
Authors: Spencer Fang, Joshua Pillai, Baharullah Mahin, Sarah Kim
Journal: Circulation (2024)

Introduction: The text generation abilities of large language models (LLMs), such as ChatGPT, can streamline the process of research and potentially expedite reviewing literature. Methods: We evaluated the capabilities of LLMs and their major susceptibilities—hallucination and goal misgeneralization—in reviewing cardiology literature. We asked 30 comprehensive questions (n=600) regarding findings from notable cardiovascular studies and randomized controlled trials (n=20) from 2016-2020 to GPT-4, GPT-3.5, and LLaMa 3. The question groups followed a format where the initial question checked for accuracy in identification, second for misgeneralization, and third for hallucination (Table 1). All questions were communicated in individual interfaces of the models to retain independence and prevent bias. Responses were then reviewed for accuracy, misgeneralizations, and hallucinations. Results: GPT-4 and GPT-3.5 did not significantly differ in accuracy (55% vs. 40%, p=0.527), with a low association (φ=0.1) and an odds ratio (OR) of 1.83 (95% CI: 0.522-6.434). Similar results were observed between GPT-4 and LLaMa 3 (55% vs. 30%, p=0.201), with an OR of 2.85 (95% CI: 0.776-10.467). For generalization, GPT-4 and GPT-3.5 also did not significantly differ (30% vs. 35%, p=0.999), with a low association (φ=0.001) and an OR of 0.80 (95% CI: 0.211-2.998). Likewise, GPT-4 and LLaMa 3 showed no significant difference (30% vs. 25%, p=0.999), with an OR of 1.29 (95% CI: 0.319-5.174). For non-hallucinations, GPT-4 and GPT-3.5 did not significantly differ (30% vs. 60%, p=0.187), with a low association (φ=0.214) and an OR of 0.33 (95% CI: 0.088-1.256). Lastly, GPT-4 and LLaMa 3 showed no significant difference (30% vs. 25%, p=0.836), with an OR of 1.50 (95% CI: 0.36-6.13). Overall, all models did not differ in accuracy, misgeneralization, and hallucination. Given the moderate susceptibilities of these models, LLMs require more training before realistic usage in cardiology. Conclusions: LLMs show potential for identifying cardiology studies, but moderate hallucination and misgeneralization render them unsuitable for this purpose. Without resolution of susceptibilities (&lt;5-10%), LLMs remain unrealistic for accurately reviewing literature.
Abstract 4136330: It’s ‘Tachy’ To Be Fooled - Adenosine Use During Leadless Pacemaker Placement to Ensure Reliable Threshold Assessment in the Setting of Tachycardia
Authors: Shreya Arvind, Madhumita Kolluri, Sindhuja Palle, Craig Moskowitz
Journal: Circulation (2024)

Introduction: Accurate assessment of pacing thresholds during permanent pacemaker implantation is critical to ensure device function and longevity. A few reports have described rate-related threshold variability during Micra TM leadless pacemaker (Medtronic Inc, Minneapolis, MN) procedures. Postulated mechanisms for this phenomenon include variable myocardial contact or micro-dislodgment, and inflammation-induced phase IV block. In this case series, we demonstrate the use of adenosine to induce transient heart block for accurate threshold assessment in patients with tachycardia during leadless pacemaker placement. Cases: A 69-year-old male with a history of atrial flutter presented with complete atrioventricular (AV) block requiring emergent transvenous pacing. A Micra placement was performed. During the procedure, the patient was tachycardic in rapid atrial flutter despite multiple doses of metoprolol. It was noted that with rapid pacing from the pacemaker at 120 pulses per minute (ppm) the threshold was ≤1V at 0.24 ms. An adequate “tug-test” was performed and at least 2 of 4 tines were noted to be fixated based on fluoroscopic motion. To confirm the capture threshold before final deployment, 12 mg of adenosine was given to induce heart block. However, at a rate of 60 ppm, there was no ventricular capture at 3V at 0.24ms. The device was repositioned and repeat threshold testing with adenosine at 60 ppm was 0.38V at 0.24ms. Pacing parameters were assessed the next day and remained stable. Similarly, a 75-year-old female with ischemic cardiomyopathy was admitted with new atrial fibrillation (AF). She then developed pauses prompting Micra placement. During initial threshold testing, she was in rapid AF despite receiving multiple doses of metoprolol. Heart block was induced with 12mg adenosine to assess the threshold at a lower pacing rate of 60 ppm. The capture threshold achieved was 0.5V at 0.24ms. Discussion: Nusbickel et al., Yoshiyama et al., and Sano et al. have reported rate dependent discrepancies in capture thresholds after Micra implantation. Our cases highlight the importance of capture threshold assessment at lower pacing rates during implantation. In patients who are tachycardic at the time of the procedure, adenosine may be useful to more reliably assess device capture threshold and determine the need for repositioning.
Abstract 4136204: Clearing Senescent Cells Improves Mouse Survival Rate Post Myocardial Infarction through Alteration of Cardiomyocyte and Immune Cell Subpopulations
Authors: Mozhdeh Mehdizadeh, francis leblanc, patrice naud, Guillaume Lettre, Eric Thorin, Gerardo Ferbeyre, Stanley Nattel
Journal: Circulation (2024)

Introduction: Cellular senescence often involves a p16-pathway, and p16 overexpression is a hallmark of senescent cells. The role of cellular senescence in myocardial infarction (MI) and any mediating mechanisms remain unclear. Aims: To investigate the effect of p16 + cell clearance on survival post MI and elucidate underlying mechanisms. Methods: We utilized INK-ATTAC transgenic mice, in which p16 + cells undergo targeted apoptosis upon exposure to AP20187 (AP). Sham and MI mice were treated with AP or vehicle (V) twice-weekly for one month, starting 3-4 hours post-MI. Survival rate improvement post MI in the AP group (Fig A, P&lt;0.001) prompted us to evaluate effects of senescent cell clearance at the cardiac cellular level and its involvement in MI-associated pathways at 3 days post-MI. The infarct and peri-infarct areas were collected and snap-frozen. Nuclei were extracted with modified gentleMACS methods; libraries were constructed using 10X Genomics. Standard software (CellRanger, Seurat) were employed for single-nuclei-RNA-seq data analysis. Results: Cardiomyocytes (CMs) showed 5 distinct subsets. CM subclusters 1 and 2 showed enrichments of genes characteristic of infarct boarder zones, while most sham CMs were found in subcluster 0, reflecting healthy-CMs. AP-treated mice exhibited a higher proportion of healthy CMs (Fig B). Differentially expressed genes (DEGs) between V and AP group were enriched in the healthy CMs, suggesting that clearance of p16 + cells improves the status of CMs post MI (Fig C). Immune-cell profiling showed that by far the largest number of DEG for AP vs vehicle were expressed in the (arginase-1) Arg1 macrophage subgroup (Fig D). The percentage of Arg1 macrophages decreased in the AP group (FDR=0.059) (Fig E). We noted significant enrichment in the hypoxia and cardiac rupture pathways in Arg1 macrophages (Fig F), correlating with the high death rate from myocardial rupture in V-mice. Conclusion: These results suggest a significant role of p16 + senescent cells in post-MI mortality, potentially through effects on cardiomyocytes and a specific macrophage subpopulation, Arg1 macrophages.
Abstract 4136267: Racial and ethnic disparities in-hospital outcomes after out-of-hospital cardiac arrest: Insight from the United States national inpatient sample
Authors: Andres Quevedo Ramirez, Joshua Ibarra, Rohan Gajjar, Hafeez Shaka
Journal: Circulation (2024)

Background: Out-of-hospital cardiac arrest (OHCA) continues to have a high mortality with an overall survivability to hospital discharge of less than 10%. Increased bystander cardiopulmonary resuscitation has resulted in better survival after OHCA. Some studies have tackled sociodemographic characteristics and rates of survival, but these are mostly localized studies with varied results. We investigated racial disparities in in-hospital mortality and mechanical circulatory support (MCS) use in OHCA. Methods: Retrospective cohort study based on the 2019-2020 National Inpatient Sample database of the Healthcare Utilization Project. Our population included patients 18 years or older with out-of-hospital cardiac arrest (OHCA) identified using ICD-10 codes. The primary risk factors examined were race/ethnicity categorized into White, Black, and Hispanic. The primary outcome was in-hospital mortality among patients with OHCA. The secondary outcome was mechanical circulatory support (MCS) use. Left ventricular assist device (LVAD), extracorporeal membrane oxygenation (ECMO), and intra-aortic balloon pump (IABP) were identified as MCS. Multivariate regression analysis was used to estimate the odds ratio. Results: During the study period, 26,640 hospitalizations with OHCA were identified, of whom 67,4% were White, 22,9% were Black, and 9,7% were Hispanic. The mean (SD) age of patients with OHCA was 65.2 (16) years old, and Black patients well as Hispanic patients had lower mean age compared to White patients (63.1 vs 63 vs 66.3 years old, p&lt;0.001). A total of 19,425 died (72.9%) and 0.9% needed MCS. Notably, more Hispanics needed MCS, compared to White and Black patients (1.7% vs 0.9% vs 0.4%, p=0.049). In the multivariate analysis, we did not find statistical significance among racial/ethnic groups regarding in-hospital mortality. However, Hispanic patients had higher odds of MCS (OR=2.4; CI 95% 1.05-5.55, p=0.039) compared to White patients. No statistical significance was found regarding the use of IABP or LVAD. Conclusion: Overall, in-hospital mortality was elevated. Moreover, our findings highlight significant racial disparities after OHCA regarding MCS use. More research is needed to identify factors of racial disparities to improve outcomes.
Abstract 4136030: Fatty acids disturb cardiomyocyte proliferation by increasing PDK4 and HMGCS2 via PPARδ activation
Authors: Shota Tanaka, Akane Hirota, Yoshiaki Okada, Masanori Obana, Yasushi Fujio
Journal: Circulation (2024)

Background: Almost all cardiac diseases are difficult to cure entirely because cardiomyocytes rarely proliferate to recover cardiac damage. In fact, most mammals have a capacity to regenerate cardiomyocytes immediately after birth. Newborn infant drastically changes cardiac metabolism from glycolysis to oxidative phosphorylation using fatty acids. Previous research revealed that lipid metabolism had a negative influence on cardiomyocyte cell cycle but the mechanism has not been clarified completely. Objective: This study was performed to elucidate the way fatty acid metabolism affects cardiomyocyte proliferation. Methods and results: Isolated and cultured neonatal rat cardiomyocytes (NRCM) were treated with the mixture of palmitic acid, oleic acid, and L-carnitine (FA mix) for 24 hours. Realtime RT-PCR revealed that FA mix increased the mRNA expressions of pyruvate dehydrogenase kinase 4 (PDK4), a fatty acid metabolism regulator, and HMG-CoA synthase 2 (HMGCS2), a ketogenic factor, as well as β-oxidation-related enzymes in dose dependent manner. Simultaneously, the results of immunofluorescent staining showed that FA mix decreased cardiomyocytes expressing Ki67, a cell cycle marker. GW501516, a peroxisome proliferator-activated receptor δ (PPARδ) agonist, also increased fatty acid metabolism factors with the reduction of Ki67 positive cardiomyocytes, whereas fenofibrate, a PPARα agonist, or pioglitazone, a PPARγ agonist, caused little or no change in these phenotypes. Moreover, NRCM pretreated with GSK3787, a PPARδ antagonist, before FA mix stimulation suppressed the upregulations of fatty acid metabolism factors and the reduction of Ki67 expressing cardiomyocytes. Finally, the lentiviral vectors which expressed PDK4 or HMGCS2 were produced to investigate these proteins suppressed NRCM cell cycle directly. Either overexpressing PDK4 or HMGCS2 decreased Ki67 positive NRCM without the upregulation of each other or β-oxidation-related enzymes. Conclusion: Fatty acids disturbed NRCM proliferation by upregulating PDK4 and HMGCS2 through the activation of PPARδ independently from β-oxidation.
Abstract 4135985: Association of Plasma Cystatin-C with Cancer Risk in Individuals with and without Cardiovascular and Chronic Kidney Disease: An Atherosclerosis Risk in Communities (ARIC) Study
Authors: Omar Elsayed, Xiaoling Wang, Neal Weintraub, Ryan Harris, Biplab Datta, Steven Coughlin, Corinne Joshu, Josef Coresh, Elizabeth Platz, Avirup Guha
Journal: Circulation (2024)

Background: While previous studies suggested a relationship between circulating Cystatin-C (Cys-C), a cysteine protease inhibitor involved in regulating tissue inflammation and a renal filtration marker, and both cancer and CVD, they often lacked long-term follow-up or did not account for the impact of CVD on the relationship between Cys-C and cancer. Methods: We included participants from the Atherosclerosis Risk in Communities (ARIC) study followed from visit 2 (1990-1992) through 2015. Plasma Cys-C level was measured by SomaScan. Other renal filtration markers beta-2 microglobulin (B2M) and beta-trace protein (BTP) were used to compare their cancer association with Cys-C. Incident cancer was ascertained by state cancer registry linkage supplemented with medical records. After adjusting for age, sex, race, and study center, adjusted hazard ratios (aHR) of total and site-specific cancers were estimated using Cox proportional hazards regression stratified by baseline chronic kidney disease (CKD) and CVD status. Results: Among 10,869 individuals (median age of 56.9 years, 55% female, 25% Black, 74% White), 3352 incident cancers were ascertained over a median follow-up of 22.9 years. Among 9585 individuals with no history of CKD or CVD, higher Cys-C was significantly associated with a higher risk of total (aHR 1.22, 95%CI 1.02-1.46), bladder, lung, colorectal, and hematologic malignancies. Among 1,050 individuals with CVD, but not CKD, Cys-C level was not associated with total cancer (aHR 1.22, 95%CI 0.74-2.01), but was significantly inversely associated with colorectal (aHR 0.19, 95%CI 0.05-0.76) and positively associated with post-menopausal breast (aHR 4.52, 95%CI 1.05-19.40) cancer risk. In individuals with CKD but not CVD, Cys-C was negatively associated with bladder (HR 0.08, 95%CI 0.0-0.77) and lung (0.23, 95%CI 0.06-0.82) cancers. Lastly, those with both CKD and CVD showed higher hematopoietic and lymphatic cancer with higher Cys-C (HR 4.68, 95%CI 1.32-16.60). Similar patterns were observed for B2M and BTP proteins. Conclusions: Our study highlights the intricate relationship between various renal filtration markers and cancer risk. It suggests that they may play a significant role in cancer development among the general population and CVD patients but not CKD patients. Further research should explore the biological mechanism underlying these associations with even more CKD cases to refine risk estimates. Funding: NHLBI, NCI, NPCR
Abstract 4136182: Usefulness of Lymphocyte-to-Monocyte Ratio in Predicting Late Recurrence of Atrial Fibrillation after Catheter Ablation and its Association With the Type of Atrial Fibrillation
Authors: Shunsuke Tamaki, Hiroshi Kawakami, Tomoki Fujisawa, Ryo Miyabe, Yasuhisa Nakao, Shigehiro Miyazaki, Yusuke Akazawa, Toru Miyoshi, Akinori Higaki, Fumiyasu Seike, Haruhiko Higashi, Kazuhisa Nishimura, Katsuji Inoue, Shuntaro Ikeda, Osamu Yamaguchi
Journal: Circulation (2024)

Introduction: Leukocyte activation is reported to be an important inflammatory pathway underlying atrial fibrillation (AF). The lymphocyte-to-monocyte ratio (LMR) is a novel, cost-effective, and widely available marker of inflammation. Research Questions: The usefulness of LMR in predicting late recurrence of AF (LRAF) after catheter ablation (CA), and the impact of AF type on its usefulness, have not yet been elucidated. Goals: We aimed to elucidate the association between LMR measured just before CA and the risk of LRAF in patients who underwent CA for AF, and to investigate whether the type of AF impacts the predictability of LMR for LRAF. Methods: We enrolled 597 consecutive patients with AF (median age, 65 years; 32% female; 334 patients with paroxysmal AF [PAF] and 263 patients with persistent AF [PeAF]) who underwent initial radiofrequency CA. LMR was measured within 3 days prior to the date of CA, and calculated by dividing the absolute lymphocyte count by the absolute monocyte count using the same blood samples. Any detectable atrial tachyarrhythmia lasting for longer than 30 s beyond a 3-month blanking period after the procedure was considered as LRAF. Patients were followed-up for a maximum of 3 years. Results: During a median follow-up of 24 months, LRAF occurred in 215 patients (96 with PAF and 119 with PeAF). Although there was no significant difference in LMR between patients with and without LRAF in PAF (5.3 [4.1–6.7] vs 5.2 [4.0–6.6], p=0.403), LMR in patients with LRAF was significantly lower than those without LRAF in PeAF (4.7 [3.9–6.4] vs 5.6 [4.5–6.8], p=0.015). Multivariate Cox analysis showed that LMR was an independent predictor of LRAF in PeAF (p=0.008), but not in PAF (p=0.662). Receiver operating characteristic curve analysis revealed that an LMR of 4.8 was a fair discriminator for LRAF in PeAF. Although there was no significant difference in the risk of LRAF between the patients with lower (LMR&lt;4.8) and higher LMR (LMR≥4.8) in PAF, patients with lower LMR had a significantly higher risk of LRAF than those with higher LMR in PeAF (Figure). Conclusions: Pre-ablation LMR was shown to be useful for predicting LRAF in patients with PeAF who underwent CA for AF, while not in patients with PAF.
Abstract 4135791: Bleeding risk with non-vitamin K antagonist oral anticoagulants versus single antiplatelet therapy: A systematic review and meta-analysis of randomized controlled trials
Authors: Geethan Baskaran, Michael Wang, Ghazal Razeghi, Richard Ma, Louis Park, Manasi Tannu, PJ Devereaux, William McIntyre, Jeff Healey, David Conen
Journal: Circulation (2024)

Background: While non-vitamin K antagonist oral anticoagulants (NOACs) are more effective than single antiplatelets (mostly low-dose aspirin) at reducing stroke risk in patients with atrial fibrillation (AF), differences in bleeding risk between NOACs and single-dose antiplatelets across various populations remain unclear. Aim: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing bleeding outcomes of NOACs versus single antiplatelet therapy. Methods: We searched MEDLINE, EMBASE, and CENTRAL to June 2024 for RCTs that compared NOAC (therapeutic doses used for stroke prevention in AF patients) versus single antiplatelet therapy for a treatment duration of ≥3 months. For the meta-analyses, we used fixed-effects models and reported results as summary risk ratios (RRs). We used Risk of Bias 2 and GRADE to assess the quality and certainty of the evidence. Results: Eight RCTs with 26,194 participants were included. Mean follow-up time was 18 (±13) months. NOACs included in the studies were apixaban (4 studies), rivaroxaban (2 studies), and dabigatran (2 studies). All studies used low-dose aspirin as the comparator. When compared to aspirin, NOACs had a higher risk of major bleeding (326/13107 [2.5%] vs. 239/13087 [1.8%] events; RR 1.36 95% CI 1.15-1.60, I 2 =52%, 8 trials; high certainty) (Figure A), gastrointestinal bleeding (104/8803 [1.2%] vs. 74/8788 [0.8%] events; RR 1.39; 95%CI, 1.04-1.87; I 2 =0%; 5 trials; high certainty), and clinically relevant non-major bleeding (318/10397 [3.1%] vs. 230/10395 [2.2%] events; RR 1.38; 95%CI, 1.17-1.63; I 2 =16%; 5 trials; high certainty). There was no difference in the risk of intracranial hemorrhage (88/13107 [0.7%] vs. 84/13087 [0.6%] events; RR 1.04, 95%CI 0.78-1.41; I 2 =48%; 9 trials; high certainty) (Figure B) nor fatal bleeding (22/12412 [0.2%] vs. 28/12392 [0.2%] events; RR 0.78; 95%CI, 0.45-1.36; I 2 =8%; 6 trials; high certainty). Conclusion: When compared to aspirin, NOACs are associated with an increased risk of major bleeding and clinically relevant non-major bleeding, but not intracranial hemorrhage. These data are important to inform patients about the risks of antithrombotic treatment.
Abstract 4136413: AV Junctional Ablation in the Era of Conduction System Pacing: Just Rate Control or also Rhythm Control?
Authors: Nicholas Mencer, Ritesh Patel, Ryan Brunetti, Mishal Mumtaz, Shoaib Khan, Nathan Einhorn, Bengt Herweg
Journal: Circulation (2024)

Background: Rate and rhythm controlling therapy in patients with atrial fibrillation (AF) are theoretical concepts, however, in clinical practice there is a substantial overlap between these strategies. AV junctional (AVJ) ablation is the ultimate form of rate control; however, it may result in rhythm control as well. Hypothesis: We hypothesize that individuals that underwent AVJ ablation for AF have a decrease in their AF burden after the procedure. Goals: The purpose of our study was to determine the outcome of AVJ ablation in patients with AF, in respect to atrial rhythm and AV synchrony. Methods: Retrospective review of AF patients that underwent AVJ ablation with prior or de novo conduction system pacing (CSP) lead. Included were only patients with a cardiac monitor/device allowing assessment of AF burden prior to AVJ ablation. Results: Thirty-six patients were identified, age 74±5 years, 14 male (39%), 15 paroxysmal AF (42%), 10 persistent AF (28%), 11 longstanding persistent AF (31%). 25/33 patients (76%) had a history of AF ablation. All patients underwent implantation of, or had a prior, CSP lead [His bundle pacing n=11 (31%), LBBAP n=25 (69%)]. The heart rate decreased from 89±28 bpm pre procedure to 78±7 bpm post-AVJ ablation, p=0.01. The spontaneously conducted QRS complex prior to AVJ ablation was 116±34 ms and the QRS during CSP after AVJ ablation was 129±25 ms, p=0.02. In the entire population, AVJ ablation resulted in a reduction of AF burden from 69±40% to 48±49%, p=0.005. Of those with persistent and longstanding persistent atrial fibrillation, 5/21 patients (24%) restored normal sinus rhythm without other intervention following AVJ ablation. Of those patients that spontaneous restored normal sinus rhythm, 3/5 had prior ablations (60%). During a follow-up of 703±524 days, LV EF improved from 42±16% to 47±13%, p=0.01 . Conclusion: Although AVJ ablation is the ultimate form of rate controlling therapy, in the era of CSP it may also result in better rhythm control in a substantial number of patients. Therefore, implantation of an atrial lead and avoidance of placing the CSP lead in the atrial channel may be advisable to assure AV synchrony.