tbuckley/cabot-search huggingface dataset:
Abstract 13255: Cardiac and Generalized <i>SGLT2</i> Deficiency Does Not Protect Against Development of Heart Failure With Reduced Ejection Fraction in Mice
Authors: Justin H Berger, Timothy R Matsuura, Caitlyn Bowman-Cornelius, Ling Lai, Teresa Leone, Jiten Patel, Russell Callaway, Zoltan Arany, Daniel P Kelly
Journal: Circulation (2023)

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), originally designed for the treatment of diabetes, exert profound cardiovascular benefit and are now the standard-of-care in all forms of heart failure (HF). The mechanism of their benefit in HF is unknown. We hypothesized SGLT2i act via an on-target, extra-cardiac mechanism to promote ketosis and improve myocardial energetics. Generalized- (gKO) and cardiac-specific (csKO) SGLT2 knockout mice were generated by breeding SGLT2 floxed mice with EIIa or αMHC Cre recombinase lines, respectively. While csKO grew and developed normally, gKO mice were slightly smaller compared to WT littermates. There was no baseline cardiac phenotype in either group. The gKO mice exhibited profound glucosuria, decreased fasting serum glucose and augmented fasting ketosis compared to controls, and comparable in magnitude to the metabolic effects of 14 days of treatment with empagliflozin (Empa, 50mg/kg/day orally) in WT mice. Targeted metabolomic analysis of gKO and Empa-treated WT mice identified increased circulating and myocardial levels of the ketone body 3-hydroxybutyrate (1.9-2.3x, p&lt;0.01), along with an increase in a subset of tricarboxylic acid cycle intermediates and C4-OH, a ketone oxidation by-product. Empa treatment in WT mice following trans-aortic constriction with apical myocardial infarction (TAC/MI) improved LV dysfunction and pathological remodeling at 6 weeks (left ventricular ejection fraction (EF) 36±6 vs 28±9, p&lt;0.03; tibia length-normalized biventricular weight 9.6±0.4 vs 11.3±1.6, p&lt;0.001). In contrast, csKO and gKO mice subjected to TAC/MI had no difference in EF, strain, ventricular hypertrophy or dilation compared to WT controls. In conclusion, generalized SGLT2 deficiency phenocopies the metabolic effects of SGLT2i treatment but neither gKO nor csKO afford cardiac protection in an established HF model. These results suggest an off-target mechanism for beneficial effects of SGLT2i in HF.
Abstract 12643: Role of Aortic Valve Replacement in Moderate Native Aortic Stenosis: A 10-year Outcomes Study
Authors: Osamah Badwan, Essa Hariri, Joseph Kassab, Habib Layoun, Warren Skoza, Serge C Harb, Rishi Puri, Grant W Reed, Amar Krishnaswamy, Lars G Svensson, Samir R Kapadia
Journal: Circulation (2023)

Background: Patients with moderate aortic stenosis (AS) exhibit high morbidity and mortality. Very limited evidence exists on the role of aortic valve replacement (AVR) in this patient population. Objectives: To investigate the benefit of AVR in patients with moderate AS compared to clinical surveillance on long-term survival. Methods: In a retrospective cohort study, patients aged ≥ 60 years with native tricuspid moderate AS between 2008-2016 were selected from the Cleveland Clinic echocardiographic database. Patients were classified as receiving AVR or managed with clinical surveillance. Clinical outcomes included all-cause and cardiovascular mortality, assessed by survival analyses and multivariable-adjusted Cox and competing risks regression, respectively. Results: We included 1,421 patients (mean age, 75.3 ± 5.4 years and 39.9% females) followed over a median duration of 6 years. Patients in the AVR group had lower risk of all-cause (adjusted HR = 0.51, 95% CI: [0.34, 0.77]; p = 0.001) and cardiovascular mortality (aHR = 0.50, 95% CI: [0.31, 0.80]; p = 0.004) compared to those in the clinical surveillance group irrespective of sex, receipt of other open-heart surgeries, and underlying malignancy. Conclusions: In patients with moderate AS, AVR was associated with favorable clinical outcomes and left ventricular remodeling patients. Figure 1 Incidence of all-cause mortality and cardiovascular mortality in patients with moderate AS in those who underwent AVR and clinical surveillance. Hazards ratios (HR) represent relative incidence of AVR versus clinical surveillance. HRs for all-cause mortality were calculated using Cox regression and for cardiovascular mortality using competing risks regression, with non-cardiac mortality as competing event. HRs were adjusted for age, sex, body-mass index, comorbidities, medications, and baseline echocardiographic data (AVA, MG, Vmax, and LVEF)
Abstract 14826: Effect of Torsemide vs Furosemide After Discharge for Acute Heart Failure Across the Spectrum of Left Ventricular Ejection Fraction: Observations From Transform-HF
Authors: Chris J Kapelios, Stephen J Greene, Robert J Mentz, Uchechukwu Ikeaba, Daniel Wojdyla, Kevin J Anstrom, Eric L Eisenstein, Bertram Pitt, Eric J Velazquez, James C Fang
Journal: Circulation (2023)

Introduction: TRANSFORM-HF trial showed no significant difference in mortality or hospitalization outcomes in patients randomized to torsemide (T) versus furosemide (F) following a heart failure (HF) hospitalization (HFH). However, outcomes and responses to some therapies differ across ejection fraction (EF) subgroups. Methods: We compared baseline patient characteristics and described treatment effects for various endpoints in TRANSFORM-HF stratified by EF: HF with reduced (EF≤40%;HFrEF) vs mildly reduced (41-49%;HFmrEF) vs preserved (≥50%;HFpEF) EFs. We also evaluated the prognostic association between EF and outcomes. Study endpoints were all-cause mortality and hospitalization at 30 days and 12 months (separately and as composites), and total hospitalizations. Results: Our analysis included 2635 patients with EF data. Participants with HFpEF were older (72 [62-79] years) with lower eGFR (52 [36-72] ml/min/1.73m 2 ) compared to the other EF cohorts, while patients with HFrEF had lower systolic blood pressure (112 [101-125] mmHg) and higher NT-proBNP levels (4554 [2368-9620] pg/ml). The neutral treatment effect for all studied endpoints did not differ across EF groups (all interaction p-values&gt;0.05, Figure 1A). There was no significant difference in the rates of mortality and/or hospitalization at 12 months between patients in the three EF groups (HFrEF 59.2, HFmrEF 61, HFpEF 63 events/100 patient-years, p=0.24, Figure 1B). Even after adjusting for covariates the relative risk or rate ratio for all endpoints did not differ across EF groups. Conclusions: Despite baseline differences between EF cohorts in TRANSFORM-HF, there were no significant differences in the study endpoints with T versus F across the EF spectrum. In contrast to previous observations, the adjusted risk ratios for all study endpoints did not differ by baseline EF. Following a HFH, there is substantial risk for all-cause mortality and subsequent hospitalization independent of EF.
Abstract 13728: Generation of a Patient-Reported Outcome Measure of Quality of Life in Heart Valve Disease
Authors: Ariel Pons, Gillian Whalley, Kate Sneddon, Crispin Jenkinson, David Morley, Sean Coffey
Journal: Circulation (2023)

Introduction: Heart valve disease (HVD) is common globally, yet there is no questionnaire measuring quality of life (QOL) across the lifespan of HVD. This limits assessment of changes in QOL in response to intervention in HVD. Research Question: What are all features of QOL in lived HVD, and how may these be best selected between to create a well-performing questionnaire? Goal: We aimed to generate a patient-reported outcome measure of QOL in common and significant types of HVD: aortic stenosis, mitral regurgitation, mitral valve disease in rheumatic heart disease, and valve repair/replacement. Methods: Participants were recruited from echocardiographic databases in two tertiary surgical centres in three phases. Phase One described QOL in interviews; Phase Two pilot-tested the questionnaire; and Phase Three selected between items using item distributions, exploratory factor analysis (EFA), and item response theory (IRT) to create the final questionnaire, called the Valve Quality of life (VALVQ). Results: In Phase One, 34 people with HVD, three family members, and five clinical experts were interviewed. Key features of QOL were physical capacity relative to ‘normal’, symptom interpretation causing reduced activity, and fatigue. In Phase Two, we showed in 62 participants that the resulting questionnaire - and its semantic differential item format - was functional. In Phase Three, 290 participants returned questionnaires. Items were removed for poor distributions, then EFA identified ‘physical capacity’ and ‘disease perception’ as key factors. A two-parameter Graded Response Model was used to generate the final 12-item VALVQ, which is shown in the attached table. Conclusion: Through application of sequential analyses across three phases, we generated the final 12-item VALVQ. It has two factors - physical capacity and disease perception - and can be deployed for future research on QOL in HVD, whether before or after intervention and across multiple forms of HVD.
Abstract 12856: Electrocardiographic T Wave Inversion and Cardiac Structure and Function
Authors: Daisuke Kamimura, Wondwosen Yimer, Robert J Mentz, Javed Butler, Amil M Shah, Oguz Akbilgic, Mobin Kheirkhahan, Maria Clarissa Tio, Arsalan Hamid, Takeki Suzuki, Michael E Hall
Journal: Circulation (2023)

Background: Electrocardiographic T wave inversion (TWI) has been associated with incident heart failure (HF) in Black Americans without known coronary heart disease (CHD). The aim of this study was to investigate the relationship between TWI and left ventricular (LV) structure and function to evaluate cardiac changes that may precede symptomatic disease among Black Americans. Methods: Among 4134 Black American participants in the Jackson Heart Study without prevalent HF or CHD at baseline. We defined TWI as having negative T wave amplitudes in each lead of the 12-lead electrocardiogram. Outcomes of interest included echocardiographic LV structure (LV mass index, LVMI, LV diastolic dimension, LVDd and relative wall thickness, RWT) and LV function (LV ejection fraction, LVEF). We investigated the associations between TWI and LV structure and function using multiple linear regression analysis. For participants with missing values in any covariate of interest, values were imputed using multiple imputation by chained equations. Results: In this cohort with median age 55 years and 65% women. The depth of the inverted T wave in leads I and aVL were positively associated with RWT (Figure). The depth of the inverted T waves in leads II, III, and aVF were associated with LVDd. The depth of the inverted T waves in all the leads except V1 and V2 were associated with LVMI, while T wave inversions in only aVF were associated with LVEF. Conclusion: The depth of inverted T waves in leads I and aVL (which were associated with incident HF with preserved EF) were associated with LV concentricity while T wave amplitudes in leads II, III, and aVF (which were associated with incident HF reduced EF) were associated with LV eccentricity. Simple electrocardiographic information may be useful for identifying patients at risk of HF (stage B/pre HF).
Abstract 15649: Human Induced Pluripotent Stem Cell-Derived Cardiac Fibroblast Assembled Extracellular Matrix Rescues Cardiac Function in an Acute Myocardial Infarction Mouse Model
Authors: Eric G Schmuck, Jasmine Giles, Timothy A Hacker, Allison Rodgers, Rachel Taylor, Timothy J Kamp, Amish N Raval
Journal: Circulation (2023)

Background: Acute myocardial infarction (AMI) is the leading cause of heart failure (HF). Therapies to curb post-AMI pathological left ventricular remodeling could reduce the burden of HF. Human iPSC derived cardiac fibroblast assembled extracellular matrix (iCFX) is a novel acellular biomaterial that consists of a unique blend of extracellular matrix proteins with tissue reparative potential. We hypothesize that direct cardiac injection of iCFX into the peri-infarct border in a mouse AMI model will restore cardiac function and reduce pathological remodeling. Methods: Acute MI was induced by permanent ligation of the left anterior descending coronary artery in 10-week immunocompetent C57BL/6 mice. iCFX was supplied by Cellular Logistics Inc, Madison, WI. One day post-AMI, mice were randomly treated with a 50 microliter epicardial injection of either PBS control, 1 mg iCFX or 10 mg iCFX. Baseline and 28-day echo were performed. Results: At baseline, there were no differences in any echo parameter between treatment groups. By 28 days post treatment, mice treated with 10 mg iCFX had increased ejection fraction ((25.8+/-3.1% (n=8) vs. (13.9+/-1.8% (n=11) p=0.001), fractional shortening ((15.5+/-2.0% (n=8) vs. 6.9+/-1.3%) (n=11) p=0.003), and cardiac output (16.0+/-2.3 ml/min (n=8) vs. 9.7+/-1.2 ml/min (n=11) p=0.002) compared to placebo treated animals. The 1 mg dosing group showed non-significant improvements in contractility parameters. Reduced end systolic and end diastolic volumes in the 10 mg group was observed, but these were not statistically significant. Conclusions: Therapeutic administration of human iCFX was associated with significant improvements in left ventricular contractility following AMI in an immunocompetent mouse model. Furthermore, a clear dose response pattern was observed.
Abstract 15170: Prognostic Implication of Left Atrial Reservoir Strain in Severe Mitral Stenosis With Low Transmitral Diastolic Pressure Gradient: Result From Long-Term Follow-Up Registry
Authors: Ha Jeong Lim, Iksung Cho, Dae-Young Kim, Kyu Kim, Seo-Yeon Gwak, Hyun-Jung Lee, Hee Jeong Lee, Chi Young Y Shim, Jong-Won Ha, Seonhwa Lee, In-Cheol Kim, KANGUN CHOI, Jang-Won Son, Geu-Ru Hong
Journal: Circulation (2023)

Background: Prognosis of severe mitral stenosis (MS) with low transmitral mean diastolic pressure gradient (MDPG) has not been fully understood with lack of long-term follow-up study. Aims: We investigated the prognostic implication in severe MS with low MDPG. Methods: We included patients with severe rheumatic MS (mitral valve area [MVA] &lt; 1.5 cm 2 ) from the Multicenter mitrAl STEnosis with Rheumatic etiology (MASTER) registry. Patients with severe MS were categorized into high (≥ 5 mmHg) or low (&lt; 5 mmHg) MDPG groups. The primary outcome was a composite of all-cause mortality and stroke. Among 1,248 patients with severe MS, 322 (25.8%) had low and 926 (74.2%) had high MDPG. Results: Their mean age was 59±13 years, 25% were men, and 74% had atrial fibrillation. Patients with low MDPG were older and had a higher prevalence of atrial fibrillation. During a mean follow-up of 6.8±5.9 years, 194 patients (15.5%) experienced composite events. Patients with severe MS and low MDPG had a higher risk of experiencing composite events compared to those with high MDPG (hazard ratio [HR]: 1.56, 95% CI: 1.15-2.12; p=0.004). Subgroup analysis with low MDPG revealed that decreased left atrial reservoir strain (LARs) was independently associated with poorer outcome (HR, 2.58, 95% CI: 1.08-6.20; p=0.034). Conclusion: Severe MS patients with low MDPG are at higher risk of adverse events compared to those with high MDPG. The assessment of LARs can be useful in identifying subgroups of low MDPG severe MS patients with poor prognosis.
Abstract 16077: Aortic Valve Thrombus and Acute Right Ventricular Failure in Recent Left Ventricular Assist Device Recipient: A Rare Case
Authors: Ricardo Chia, Brandon Boyer, Peter Pietrandrea, Nisha Giyanani, Steven Douedi, Deepak Singh, Ronald Ross, Mark Moshiyakhov, Kulpreet Barn
Journal: Circulation (2023)

Case reports of aortic root thrombus with embolism leading to right ventricular (RV) failure in patients left ventricular assist devices (LVAD) are extremely rare in the literature, and often result in significant mortality. This is a case of a 52-year-old male who recently underwent destination-therapy HeartMate 3 LVAD implantation, on chronic warfarin, with history of non-ischemic cardiomyopathy, atrial fibrillation, and heparin-induced thrombocytopenia, who presented with chest pain and dyspnea. Initial evaluation was remarkable for tachycardia, troponin of 0.7 ng/dl, BNP 705, and INR 1.68. Argatroban was initiated, along with diuresis for volume overload on examination. Transthoracic echocardiogram showed stable findings with borderline RV dysfunction. On the following day, persistent chest pain and uptrend of troponin to 34 ng/dl were concerning for acute coronary syndrome (ACS), and plans were for left heart catheterization. However, a TEE revealed partial thrombus layering in the aortic valve and sinus of Valsalva with concerns for embolization through the right coronary ostia. RV assessment showed evidence of severe dilation and acute RV failure. Patient underwent emergent RV assist device (RVAD) placement (ProtekDuo and CentriMag) by cardiothoracic surgery. After mechanical RV support, there was progressive improvement of its function, and successful RVAD decannulation was attained. The patient was recently seen in the heart failure clinic with sustained recovery. Cases of aortic root thrombus with embolism leading to ACS in LVAD patients are extremely rare. As in our case, troponin elevation, subtherapeutic INR, and aortic root thrombus, allowed early clinical recognition and appropriate management of patient’s RV failure, which is imperative for successful outcomes in LVAD patients. Aortic valve thrombus should be considered in LVAD patients presenting with ACS, and early invasive strategy without valve assessment should be cautioned.
Abstract 13063: Gut Microbiota-Derived Metabolites and Cardiometabolic Traits: Findings From a Monozygotic Twin Study
Authors: Guanhong Miao, Christopher Wu, Eric Strachan, Emily Fowler, Tamara Bacus, Jinying Zhao
Journal: Circulation (2023)

Introduction: Microbial metabolites are small chemical compounds produced by gut microbiota when it breaks down food, chemicals, or other environmental exposures. These metabolites serve as signaling molecules between the host and gut microbiota and regulate numerous aspects of host physiology, immunity, and metabolism. Hypothesis: Gut dysbiosis is associated with cardiometabolic disorders via alterations in microbial metabolites. Aims: To identify gut-microbiota-derived metabolites associated with cardiometabolic traits. Methods: Using hydrophilic interaction liquid chromatography (HILIC), we measured the relative abundances of 62 food and gut-microbiota-derived metabolites in plasma sample of 46 complete monozygotic twin pairs (34 female-female pairs, 12 male-male pairs, mean age 36.2) enrolled in the Mood and Methylation Study (MMS), an observational study designed to identify biomarkers associated with depressive symptoms using a twin design. Information for cardiometabolic traits, including body mass index, waist circumference, blood glucose, HbA1c, insulin, triglycerides, total cholesterol, HDL and LDL, was collected using standard questionnaires or laboratory methods. The association of each metabolite with cardiometabolic trait was examined by a linear mixed-effects model, adjusting for age, sex, smoking, drinking, and depressive symptoms. The co-twin correlation was accounted for by including twin pair as a random effect in the model. Results: After correction for multiple testing by false discovery rate (FDR&lt;0.05), 15 microbial metabolites were significantly associated with one or more cardiometabolic traits. Of these, 7 glycerophospholipids (e.g., PC(32:1), PC(34:4), PE(38:6)) and 2 sphingomyelins (i.e., SM(d36:1), SM(d36:2)) were positively, whereas betaine, creatinine, urea, pipecolic acid, N1, N12-diacetylspermine, and 3-chloro-L-tyrosine were negatively associated with LDL, triglycerides, total cholesterol, and HbA1c. Conclusions: Our results revealed novel microbial metabolites associated with cardiometabolic traits and support their potentially important role in mediating the interactions between gut microbiota and host pathophysiology.
Abstract 18572: Mimickers of Chiari Network in the Left Atrium
Authors: Dario Manley Casco, Ashvarya Mangla, sudhir mungee, Kavitha Kalvakuri
Journal: Circulation (2023)

Case: 84-year-old female with ischemic cardiomyopathy and severe secondary mitral regurgitation with restricted leaflet mobility due to chordae tethering and a large central regurgitant jet. She underwent trans-catheter edge to edge repair with Mitra Clip NTW. The clip was aligned in the 12 to 6 o'clock position in the middle of A2/P2 scallop and appropriate graft was obtained with good tissue bridging. The trans mitral gradient at the end of the procedure was 3 mmHg and final V-waves at 10 mmHg. After the guiding catheter was moved back to the right atrium, the transesophageal echocardiogram (TEE) showed the presence of an echo dense flickering, bubble-like mobile structure around the right upper pulmonary vein. The heart team agreed that it looked like an endothelial disruption induced by the guiding catheter. After careful consideration and using shared decision making, the patient was maintained on Eliquis for 6 months without evidence of thromboembolic phenomena. Repeat TEE showed a healed dissection flap and no echo dense structure seen previously. Discussion: Unlikely to be thrombus or air bubbles, this structure looked like what we would see in a Chiari network. Complications after Mitra Clip procedure have been well described and can be broadly divided into procedure related and device related. Endothelial disruption with the imaging characteristics shown in this case has not been described. There are no evidence-based guidelines on how to proceed with this type of complication. It is well known that endothelial damage increases the risk for thrombosis and embolic phenomena. Due to concerns of a stroke, the decision was made to start anticoagulation with the plan of redo TEE. This case demonstrates the importance of performing TEE after Mitra Clip procedure to look for lesions that would increase the risk of stroke. It also demonstrates that patients with endothelial disruption after Mitra clip may benefit from short term anticoagulation for stroke prevention.