tbuckley/cabot-search huggingface dataset:
Abstract 16297: DPP-4 Inhibitor Sitagliptin Treatment Results in Altered Myocardial Metabolic Proteome and Oxidative Phosphorylation in a Swine Model of Chronic Myocardial Ischemia
Authors: Dwight Harris, Sharif A Sabe, Mark Broadwin, Krishna Bellam, Cynthia Xu, Janelle Li, Ruhul Abid, Frank W Sellke
Journal: Circulation (2023)

Introduction: Small animal models have shown increased cardiac function and decreased infarct size with DPP-4 inhibition, but many human studies have shown increased heart failure readmission or no benefits. We seek to bridge the gap from small animal models to humans by studying DPP-4 inhibitor sitagliptin in a swine model of chronic myocardial ischemia using proteomic analysis. Methods: Thirteen Yorkshire swine underwent placement of an ameroid constrictor on the left coronary circumflex artery to model chronic myocardial ischemia. Two weeks post-op, swine received either sitagliptin 100 mg daily (SIT, n=5) or no drug (CON, n=8). After five weeks of treatment, swine underwent functional measurements and tissue harvest. Myocardial tissue was sent for proteomic analysis or analyzed with immunoblot. Results: In the SIT group compared to CON, there was a strong trend towards decreased cardiac index (p=0.06), with decreased end-systolic and diastolic volumes (all p&lt;0.05, Figure 1). Proteomics analysis identified 1,003 proteins in the non-ischemic and 728 proteins in the ischemic myocardium. The non-ischemic and ischemic myocardium had 396 and 166 significantly decreased proteins, respectively, in the SIT group compared to CON (all p&lt;0.01). This included proteins involved in the citric acid cycle (TCA), fatty acid oxidation (FAO), and oxidative phosphorylation (OXPHOS). Immunoblotting confirmed SIT was associated with decreased expression of several metabolic proteins including FAS, CPT1α, IDH1, and mitochondrial complexes I and II (all p&lt;0.05). Conclusions: In a swine model of chronic myocardial ischemia, sitagliptin treatment resulted in a trend towards decreased cardiac index and decreased expression of proteins involved in OXPHOS, FAO, and the TCA in both ischemic and non-ischemic myocardium. These metabolic and functional changes may provide some mechanistic evidence for the increased heart failure readmission in clinical studies.
Abstract 17749: Regionalization of Non-Pulmonary Vein Triggers for Atrial Fibrillation When the P Wave is Obscured Using Non-Invasive Electrocardiographic Imaging QRS-T Subtraction Algorithm
Authors: Munveer Thind, Alireza Oraii, Masahiro Sekigawa, Qing Lou, Martin Arceluz, Sara Ciaverelli, Erica Zado, Gustavo Guandalini, Timothy Markman, Rajat Deo, Robert Schaller, Saman Nazarian, Sanjay Dixit, Gregory E Supple, David S Frankel, Pasquale Santangeli, Andrew Epstein, David Callans, Matthew C Hyman, Cory M Tschabrunn, Francis E Marchlinski
Journal: Circulation (2023)

Introduction: Ablation of non-pulmonary vein triggers (NPVTs) after pulmonary vein isolation (PVI) may reduce atrial fibrillation (AF) recurrence. Localizing a trigger which initiates AF after a single atrial ectopic beat is challenging, especially in the scenario when the trigger P wave is obscured by preceding QRS-T complex. Aim: To evaluate the potential for noninvasive electrocardiographic imaging (ECGi) to localize NPVTs when the P wave morphology is superimposed on the T wave of the previous beat. Methods: We developed an algorithm which overlays and subtracts the preceding QRS-T wave complex from the QRS-T wave complex which is obscuring the P wave of interest, thus revealing the P wave morphology (Figure 1A). Resultant unobscured P waves (from multiple body surface electrodes) are then used for ECGi computation. In five patients undergoing AF ablation, after PVI, we paced from 15 atrial sites where NPVTs commonly arise, and evaluated the epicardial activation maps generated by ECGi both when pacing was timed to ensure an unobscured P wave and when timed to coincide with preceding QRS-T complex. Co-registration of CT-based ECGi activation maps with invasive electroanatomic map (EAM) allowed comparison of the earliest activation site on ECGi map from both the obscured P waves after QRS-T subtraction and unobscured P waves with true pacing locations on EAM (Figure 1B). Results: From 146 pacing sites in our patient cohort, for the unobscured P waves, median distance between earliest site on ECGi map and EAM pacing location was 16 mm (10-21 mm), and for obscured P waves after QRS-T subtraction, median distance was also 16 mm (12-23 mm) (Figure 1C). Conclusion: Using a QRS-T subtraction algorithm, ECGi can approximate origin of paced P waves whether P wave is unobscured or obscured by the preceding QRS-T complex. Spontaneous NPVT P waves are commonly obscured by the QRS-T wave and the ability to rapidly localize an early coupled P wave may facilitate NPVT mapping and ablation.
Abstract 16737: Explantation of LVAD in Recovered Alcohol Induced Cardiomyopathy
Authors: Jenna Campbell, Samir P Mehta, Muhammad A Shakir, Sourin Banerji, Syed Ali Hamid
Journal: Circulation (2023)

Durable Left Ventricular Assist Device (LVAD) is an important modality for bridge or destination therapy for patients with end-stage heart failure. However, there is a paucity of evidence guiding management for LVAD explantation in patients with sufficient myocardial recovery as this only occurs in 1-3% of cases. We present a case of a patient with LVAD placement due to alcoholic cardiomyopathy with subsequent removal of his LVAD three years later. Description of Case: A 51-year-old male with a history of alcohol induced cardiomyopathy with an LV ejection fraction of 10% s/p Heartmate II LVAD implant 3 years ago was evaluated for LVAD explantation. Over the course of one year, LVAD speed was decreased and ejection fraction (EF), cardiac output (CO) and cardiac index (CI) were monitored. Prior to explantation, the patients EF was 50% with a CO of 5.6L/min and CI 2.7 L/min/m2. Following successful explantation, a repeat echocardiogram 3 months later revealed an EF of 45%. Right heart catheterization revealed CO of 5.3L/min and CI 2.6L/min/m2. Patient was discharged on guideline directed medical therapy with continued improvement. Discussion: Mechanical, histological, and biochemical myocardial improvement has been described in LVAD recipients. There is a paucity of data to guide recovery assessment and candidacy for explantation. The 2023 ISHLT guidelines have attempted to synthesize the available data and outline the major considerations. Assessment should be done at low LVAD speeds with incorporation of data from patient’s clinical status, echocardiography, right heart catheterization, and cardiopulmonary exercise testing. Utilization of LVAD as a bridge to recovery was feasible in our patient given careful assessment of recovered cardiac function as outlined by aforementioned criteria. LVAD explantation after heart recovery remains a rare phenomenon. As access to cardiac transplantation remains limited, consistent use of guideline directed medical therapy allows for the possibility of heart recovery along with explantation. We present a case of successful and maintained myocardial recovery after LVAD explantation. Cases such as this would benefit from standardization of LVAD explantation guidelines for optimal long-term survival for patients.
Abstract 12796: N-Terminal Pro-B-Type Natriuretic Peptide Levels for Determining Long Term Prognosis in Patients With Non-ST-Elevation Myocardial Infarction (NSTEMI); a Systematic Review and Meta-Analysis
Authors: Abhigan Babu B Shrestha, Nischal Mainali, Shubham Shrestha, Sajina Shrestha, Dr. Bikash Karki, Sushil Neupane, Bhaskar Jha, Apurwa Jha, Yub Raj Sedhai, Anupam Halder, Ankush Asija, SHUMNEVA SHRESTHA, Suju Bhattarai, Vikash Jaiswal
Journal: Circulation (2023)

Introduction: The utilization of the biomarker N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) holds diagnostic value for identifying heart failure and acute coronary syndromes. However, its long-term prognostic significance in patients with non-ST-elevation Myocardial Infarction (NSTEMI), a subtype of acute coronary syndromes, remains inadequately explored. Hypothesis: This meta-analysis aims to investigate the correlation between NT-proBNP levels and the subsequent occurrence of adverse clinical outcomes in individuals with NSTEMI. Methods: A systematic search was conducted on PubMed, Google Scholar, Science Direct, Cochrane, and Embase, encompassing articles published until June 2023. The highest recorded NT-proBNP value was utilized for analysis, considering a follow-up duration of at least 30 days. Odds ratios (OR) were synthesized using the random-effects DerSimonian-Laird model, with statistical significance set at a p-value &lt;0.05. Results: The study involved 8 articles, comprising a total of 7,921 patients, of whom 7,161 were diagnosed with NSTEMI. The analysis examined the relationship between NT-proBNP levels and clinical outcomes in NSTEMI patients over an average follow-up period of 19.85 months. Elevated NT-proBNP levels exhibited a significant association with increased odds of Major Adverse Cardiac Events (MACE) [OR 2.56, 95% CI: 1.58-3.53, I2=94.06%, p&lt;0.001], all-cause mortality [OR 2.54, 95% CI: 0.53-4.55, I2=76.96%, p=0.01], and myocardial infarction (MI) [OR 1.10, 95% CI: 0.56-1.63, I2=0.00%, p&lt;0.001]. Conclusions: The elevated NT-proBNP levels in patients with NSTEMI are significantly associated with long-term adverse cardiovascular outcomes. Consequently, NT-proBNP can serve as a valuable tool for assessing the risk of unfavorable cardiac events. However, further extensive investigations are warranted to validate these results on a larger scale.
Abstract 17087: Novel Machine Learning Models to Enhance and Automate Cardiovascular Outpatient Triage for Patients With Atrial Fibrillation
Authors: Gurukripa N Kowlgi, Gavin Schaeferle, Yu-Li Huang, Lezli Kuster, Maribeth Jensen, Malini Madhavan
Journal: Circulation (2023)

Introduction: Atrial fibrillation (AF) is the most prevalent arrhythmia, placing a substantial burden on the healthcare system. Patients with AF are cared for in a variety of settings including primary care and cardiology clinics, while some require cardiac electrophysiology (EP) clinics offering specialized drugs or procedures. Appropriate triage of AF referrals to these specific clinics will lead to timely and appropriate care and reduce inefficiency in the health system. Goal: To develop a machine learning (ML) model to triage AF referrals to a large Cardiology center to either the Cardiology or EP clinic based on likelihood of requiring an invasive EP procedure or initiation of antiarrhythmic drug. Methods: We retrospectively analyzed 6,755 patients who were referred to CV with referral diagnosis of AF (mean age 70 ± 11 years, 66% male). We employed multiple input variables to predict the suitability for EP clinic defined as need for initiating an antiarrhythmic drug or an invasive EP procedure. These encompassed patient demographics, relevant comorbidities, medications, prior procedures, medical notes analyzed using natural language processing (NLP), and Holter monitoring data. Results: For internal referrals, XG boost model performed the best with AUC at 79%, accuracy at 72%, and F1 score at 68%. This model produces true positive (TP) at 68% and true negative (TN) at 74%, which was better in comparison with triaging using NLP only (AUC = 69%, TP = 58%, TN = 61%), Holter only (AUC = 52%, TP = 51%, TN = 77%), and NLP/Holter (AUC = 67%, TP = 60%, TN = 60%). When supplementing ML model with Holter readings on average HR ≥ 100 and maximum HR ≥ 150, the results can be improved to TP at 70% and TN at 73%. Conclusions: Our model effectively identifies patients who are more likely to require specialized EP care, enabling the automation and increased efficiency of the AF referral triage process. Prospective validation studies are paramount in determining the true value of this tool.
Abstract 13753: Cumulative Circulating Monocyte Load is Associated With All-Cause Mortality: A Longitudinal Cohort Study
Authors: Dan Wu, Yulong Lan, xiong ding, Baoyu Feng, Chutao Wu, Wei Wang, Wencan Xu, Shouling Wu
Journal: Circulation (2023)

Introduction: Monocytic inflammation has been increasingly linked to diverse cardiometabolic risk factors and many age-related pathologies. Hypothesis: Cumulative monocyte counts (CumMON) are associated with and predictive of all-cause mortality. Methods: Retrospective analyses of data among 43,681 Han Chinese participants from a real-world, prospective cohort (Kailuan Study). Multivariable-adjusted Cox regression analyses were conducted to examine CumMON-associated risks for all-cause mortality. Results: Over a median 7.76 (IQR: 7.47-8.03) years of follow-up, 2,810 all-cause deaths were documented. Elevated monocyte load was significantly associated with higher mortality rates ( Figure 1 ). Each 1-SD increase in CumMON was associated with a 15% increase in all-cause death (1.15, 95% CI: 1.11-1.20) after adjusting for other risk factors. Higher death incidences and CumMON-associated mortality risks (per-SD increment) were observed in elderly individuals, participants with diabetes (1.18, 95% CI: 1.10-1.27), hypertension (1.16, 95% CI: 1.11-1.21), impaired renal function (1.18, 95% CI: 1.13-1.24), increased LDL-C (1.21, 95% CI: 1.15-1.28 for LDL≥2.6 mmol/L) or decreased HDL-C levels (1.21, 95% CI: 1.12-1.31), but not with CVD or cancer. There were significant supra-additive interactions between elevated CumMON and diabetes (RERI: 0.26, 95% CI: 0.04–0.48), hypertension (RERI: 0.35, 95% CI: 0.12–0.57), and old age (≥60 years) (RERI: 0.46, 95% CI: 0.07–0.85). The addition of cumulative monocyte load into the multivariable model significantly improved the prediction performance of all-cause death (net reclassification improvement: 12.05%; P &lt;0.0001). Conclusions: Elevated cumulative monocyte load is significantly associated with all-cause death and improves risk prediction. Chronically elevated monocytes supra-additively enhance the mortality risk among those with old age, diabetes, or hypertension.
Abstract 15404: Exercise and Sports Participation is Associated With Improved Quality of Life in Young Patients With Heritable Thoracic Aortic Disease
Authors: Theodore J Millette, Peter N Dean, Randy K. Ramcharitar, Oliver Monfredi, Matthew Thomas, Mark Conaway
Journal: Circulation (2023)

Introduction: Traditionally, patients with heritable thoracic aortic disease (HTAD) have been restricted from competitive sports due to concerns over acute aortic dissection. Patients with HTAD also exhibit lower quality of life (QOL) and physical fitness than general populations. Murine data suggests exercise improves aortic health and does not contribute to aortic enlargement. Hypothesis: Exercise and competitive sports participation will be associated with improved QOL in HTAD patients. Aims: Investigate the effect of lifetime exercise ‘dose’ and competitive sports participation on QOL in patients aged 15-35 with syndromic HTAD [Marfan syndrome (MS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS)] and non-syndromic HTAD. Methods: This cross-sectional study employed a questionnaire to assess lifetime exercise exposure and utilized the PedsQL QOL Inventory. We developed an Exercise Score (ES) to quantify lifetime exercise exposure based on questionnaire results (3 points for competitive sports season, 1 point for recreational sport season. Questionnaires were completed via telephone interview with complimentary medical chart review. Results: Of the forty patients enrolled, the mean age was 26 years. The diagnosis was MS in 82.5%. Despite 87.5% of patients being restricted by their cardiologist, 65% reported competitive sports participation and 92.5% reported some lifetime recreational exercise. The median ES for our population was 19. Participants with an ES greater than the median had a significantly better total QOL score compared to participants with an ES below the median (78 vs 65, p=0.03). There was no difference in aortic size or need for surgical intervention between those above and below the median ES. This also held true for those who did and did not participate in competitive sports. There was a strong positive correlation between the amount of current exercise (days-per-week) and total QOL score (corr=0.55, p&lt;0.001). Conclusions: Increased lifetime exercise exposure and current physical activity levels were associated with improved QOL in young adults with HTAD. There did not appear to be a detrimental effect of exercise on aortic size or need for surgical intervention.
Abstract 14283: Brain-Mediated Cardioprotective Actions of Leptin: Potential Role of Brown Adipose Tissue and Its Release of Extracellular Vesicles
Authors: Ana C Omoto, Ivan Vechetti, Blake Rule, Jussara M Docarmo, Alexandre A Da, Sumaya Zenun, Odecio Tosta, Kylie Larson, Nikaela Aitken, Benjamin Nelson, Zhen Wang, Xuan Li, Alan J Mouton, John E Hall
Journal: Circulation (2023)

Background: We recently demonstrated that leptin has powerful central nervous system (CNS) actions that dramatically improve cardiac function following ischemia/reperfusion (IR) injury. How the brain communicates with the heart during CNS leptin infusion to improve cardiac function is unknown. One potential mechanism is activation of brown adipose tissue (BAT) which may be an important source of extracellular vesicles (EVs) carrying cardioprotective microRNAs (miR), including miR-125b-5p. Hypothesis: We investigated whether BAT contributes to the cardioprotective effect of CNS leptin infusion and the potential role of EVs carrying the miR-125b-5p in this protection. Methods: Male Sprague-Dawley rats were submitted to interscapular BAT ablation (iBATx) and instrumented with an intracerebroventricular (ICV) cannula in the brain lateral ventricle. After recovery and baseline assessment of cardiac function by echocardiography (ECHO), myocardial IR was induced by temporary ligation of the left anterior descending coronary artery. Vehicle (saline, 0.5 μL/hr) or leptin (0.62 μg/hr) was infused ICV chronically for 28 days using osmotic pumps. Cardiac function was assessed weekly by ECHO. Another set of animals with intact iBAT was treated with ICV leptin or vehicle for 4 weeks and had their iBAT collected for EVs isolation and quantification. Expression of the miR-125b-5p was measured in the heart of leptin treated rats with intact iBAT or iBATx. Results: Compared to vehicle-treated animals, ICV leptin infusion increased iBAT-derived EVs and removal of iBAT prevented leptin’s CNS-mediated cardioprotective effects after IR injury as indicated by a lack of improvement in ejection fraction (26±6 vs 41±3%) and stroke volume (162±31 vs 275±19μL) at week 4 post-IR. Expression of the mature miR-125b-5p was increased in the heart of ICV leptin treated rats and iBATx abolished this effect. Conclusion: These results indicate that the BAT plays an important role in mediating the cardioprotective effect of CNS leptin administration after IR injury and suggest that iBAT-derived EVs may be involved in delivering the miR-125b-5p to the heart during central leptin infusion. AHA 835218, 1R01HL163076, P20GM104357, and P20GM104320-07
Abstract 13295: The Effects of Short-Term Exposure to Fine Particulate Matter and Ozone on Attending Outpatient Clinic Visit Appointments Among Patients With Depressive Symptoms
Authors: Heidi T May, Daniel Bride, Tami L Bair, Viet T Le, Stacey Knight, Jeffrey L Anderson, Kirk U Knowlton, Elizabeth A Joy, Benjamin D Horne
Journal: Circulation (2023)

Background: Air pollution is increasingly recognized as an environmental risk factor for mental health. However, data regarding the short-term influence on depressive symptoms are limited. It is known that depressed patients (pts) tend to be less adherent to prescribed medical regimens, including appointments. Therefore, we sought to determine how depression during times of increased particulate matter (PM 2.5 ) and ozone during winter inversion (Nov-Mar) and wildfire seasons (June-Oct) affected pt behavior of attending clinic visit appointments. Methods: Pts (n=142,930) who completed a PHQ-9 as an outpatient between Mar 2003-Apr 2022 and resided on Utah’s Wasatch Front were studied. PHQ-9 results were used to classify depression by no depressive symptoms (&lt;10) or any depressive symptoms ( &gt; 10), with further stratification into severe ( &gt; 20). A case-crossover design was used with odd ratios computed by Poisson regression. Results: A total of 43% (n=60,724) of pts had depressive symptoms, with 25% (n=15,278) being severe. Depressed pts were younger (37 vs. 45 yrs), female (62% vs. 56%), more often smoked (24% vs. 17%), and had fewer comorbidities. The likelihood of attending clinic visits was decreased when the moving average (mAvg) of PM 2.5 was increased in the 2 days and week prior among those with depression, particularly when severe (Figure a). Levels of PM 2.5 on lag day 0 did not affect visit attendance. Increases in ozone were associated with a decrease in clinic attendance (Figure b). Air pollution levels &gt;7 to 28 days prior were not associated with clinic attendance. Conclusion: Short-term increases in air pollution, particularly in average PM 2.5 during inversion season, in the days and week prior were associated with a decrease in attending clinic visit appointments among depressed pts. These results could have healthcare delivery implications since people with depression were less likely to show up to non-emergent medical visits when the air has been polluted.
Abstract 17011: Correlation of Surface Atrial ECG Dominant Frequency to Intracardiac Atrial Electrogram Dominant Frequency
Authors: Ghaith Zaatari, Jorge Bohorquez, Laura McDermott, Raul Mitrani, Catherine Blandon, alex velasquez, Litsa Lambrakos, Jeffrey J Goldberger
Journal: Circulation (2023)

Background: The surface Atrial ECG (A-ECG) is an underused tool in persistent atrial fibrillation (PeAF) that can provide dominant frequency (DF) of atrial activation. The association between A-ECG DF and left (LA) and right atrial (RA) DF has not been established. Research Question: Does surface A-ECG DF correlate with intracardiac DF? Aims: To investigate the correlation between A-ECG peak DF and peak DF of intracardiac RA and LA electrograms (EGM) in patients with PeAF. Methods: Thirty-two patients (age 63±9 years; 71% males) with PeAF underwent 5-minute epochs of surface ECG and comprehensive LA (261.5±185.1 sites/patient) and RA (211.5±174.6 sites/patient) intracardiac mapping with 15 second recordings. The A-ECG was derived by QRST subtraction and independent component analysis filtering, and divided into overlapping10-second windows which were subjected to Fast Fourier Transform (FFT). 4 were excluded for significant artifact. A-ECG DF was calculated for each lead from the power spectrum as the average of all 10-second segments. Peak A-ECG DF was determined by regional lead location and for all 12 leads. The intracardiac EGM DF was calculated from the FFT, and peak RA and LA DF was determined. Results: A-ECG peak DF was significantly lower than intracardiac peak DF 6.08±0.64 vs 9.72±1.19 Hz, p&lt;0.0001(LA: 9.72±1.20 Hz, p&lt;0.0001; RA: 8.40±0.80 Hz, p&lt;0.0001). Figure shows that A-ECG peak DF correlated with peak RA DF, r=0.77 (p&lt;0.0001), but not with peak LA DF (r=0.31, p=0.10). Regional A-ECG lead group DF correlated with RA DF (Inferior (II, III, aVF): r=0.79, p&lt;0.0001; Lateral (I, aVL, V5-6): r=0.78, p&lt;0.0001; Anterior (V1-3): r=0.75, p&lt;0.0001) but not with peak LA DF. Conclusion: Surface A-ECG DF correlates with intracardiac RA DF and not LA DF. As in atrial flutter, the RA plays a prominent role in the surface ECG manifestation of the f waves. Further study is needed to determine whether A-ECG DF can be used to identify RA versus LA drivers that may require ablation.