tbuckley/cabot-search huggingface dataset:
Abstract 4147575: Outcomes of Utilizing Sodium Glucose Transporter Inhibitors Following Acute Myocardial Infarction: A Comprehensive Meta-Analysis
Authors: Mustafa Suppah, Mariam Desouki, Mohammed Ali, Alaa Mohamed, Menna Keshk, Ali Moradi, Austin Saugstad, Hursh Naik, Pallavi Bellamkonda, Said Alsidawi
Journal: Circulation (2024)

Introduction: Acute myocardial infarction (AMI) remains a leading cause of morbidity and mortality worldwide. In the quest for improved therapeutic strategies, the addition of Sodium Glucose Transporter Inhibitors (SGLTis) to the treatment regimen has garnered considerable attention. This meta-analysis endeavors to shed light on the efficacy of SGLTis in short-term cardio-renal protection post-AMI. By synthesizing evidence from diverse studies. Methods: Adhering to the PRISMA guidelines, a meticulous systematic review and meta-analysis were conducted. Comprehensive literature searches across PubMed, Web of Science, Scopes, and Google Scholar were performed. Inclusion criteria comprised four Randomized Controlled Trials (RCTs), one retrospective cohort, and one observational study, investigating the effects of SGLTis versus placebo on AMI patients, irrespective of diabetic status. Our analysis included the following outcomes: acute kidney injury, all-cause death, cardiovascular mortality, cardiac death, composite of cardiovascular death/hospitalization for heart failure, and NT-proBNP levels. Results: Our analysis encompassed six scientific articles involving 7238 patients. SGLTIs exhibited a notable favorable effect solely on acute kidney injury (P value=0.001, 95% CI [0.46-0.82]). Conversely, no significant benefit was observed in other short-term outcomes, including all-cause death, cardiovascular mortality, cardiac death, composite of cardiovascular death/hospitalization for heart failure, and NT-proBNP levels. These results align with previous studies suggesting the renal protective effects of SGLTIs but highlight the need for further research to clarify their overall cardiovascular benefits in AMI patients. Conclusion: Incorporating SGLTis into the therapeutic armamentarium of AMI patients, irrespective of diabetic status, demonstrated a discernible advantage solely concerning acute kidney injury. However, no appreciable benefit was discerned across other assessed metrics. These findings underscore the need for further exploration and tailored therapeutic strategies in the management of post-AMI patients.
Abstract 4147122: Automated quantification of amyloid burden in cardiac amyloidosis
Authors: Francesco Greco, Alberto Aimo, Veronica Musetti, Alessandra Celi, Syria Polito, Vincenzo Castiglione, Giuseppe Vergaro, Michele Emdin, Angela Pucci
Journal: Circulation (2024)

Background: Cardiac amyloidosis (CA) involves the accumulation of amyloid fibrils in the extracellular cardiac spaces, increasing the extracellular volume (ECV) and correlating with poorer outcomes. Accurate quantification of cardiac amyloid is prognostically valuable but challenging with current manual methods using Congo-Red (CR)-stained tissue. We developed a digital pathology pipeline for automated quantification of cardiac amyloid on CR-stained endomyocardial biopsies (EMBs). Methods: We analyzed 20 consecutive left ventricular EMBs with CA (AL, n=12; ATTR, n=8) and 10 EMBs with cardiac hypertrophy (CH) and CA excluded. Amyloid was semi-quantitatively assessed as focal, multi-focal or diffuse by a cardiac pathologist. Polarized light images were converted into negative images using MATLAB to obtain bright field images, normalized using modified Reinhard normalization, and imported into QPath software. Images underwent color deconvolution to isolate the negative of the apple-green color. An intensity threshold on the amyloid channel detected positive pixels. Total tissue area was calculated by intensity threshold of the bright field image. Results: Standardized staining and image acquisition using automated machines and fully closed polarizer filters resulted in consistent histological staining. Residual staining variabilities were removed by applying a modified Reinhard normalization, equalizing the median of the image channels in the L*a*b color space. Conversion of dark field polarized images to negative allowed for the use of standard color deconvolution algorithms to isolate the negative apple-green channel and to use thresholding to quantify positive pixel. Amyloid quantification showed significantly higher amyloid percentages in positive controls (mean 6.21%) compared to negative controls (mean 2.29%) with a 0.05 threshold. The method was applied to six independent acquisition of the same section to assess reproducibility. The variation coefficient of the percentage of amyloid-positive pixels in the replicates was 11.6%, confirming method reproducibility. Conclusions: A digital pathology pipeline quantifying amyloid birefringence areas and, in most cases, differentiated it from collagen birefringence. Automated amyloid quantification simplifies EMB sample analysis and provides valuable information for risk prediction.
Abstract 4147087: Impact of fractional flow reserve measurement on outcomes in the invasive arm of the ISCHEMIA trial
Authors: Ayesha Singh, John Rodman, David Brown
Journal: Circulation (2024)

Introduction: Fractional flow reserve (FFR) is an invasive, lesion-specific surrogate for myocardial ischemia. The use of FFR to guide lesion selection for revascularization has been shown to improve outcomes compared to an angiographic approach because it allows revascularization of lesions based on hemodynamic significance. Purpose: To compare the outcomes of patients randomized to the invasive (INV) arm of the ISCHEMIA trial who underwent FFR during initial angiography with those whose treatment was guided by angiography alone. Methods: The ISCHEMIA data set was obtained from the NHLBI. Subjects randomized to the INV arm who underwent FFR were compared to those who underwent angiography alone. Unadjusted cumulative event probabilities were estimated using the Kaplan-Meier method. Multivariable Cox proportional hazards analysis was used to estimate the independent impact of FFR on outcomes. Primary endpoint of interest was cardiovascular death (CV) death or MI. Results: Of the 5,179 patients with chronic coronary syndromes and at least moderate ischemia on stress testing, 2,588 were randomized to the INV strategy, 2,475 underwent angiography and 2,210 had baseline data available for analysis. Of these, 410 (19%) had FFR performed during diagnostic angiograms. Females comprised 24% of FFR patients and 24% of non-FFR patients (P=0.85). FFR patients were older than non-FFR patients (65.7 [8.7] years vs. 64.3 [9.6] years, P=0.006). The incidence of hypertension, diabetes, smoking, or prior MI at baseline did not differ between groups. Fewer FFR patients had severe ischemia at baseline (45% vs. 52%) and more had mild or moderate ischemia (54% vs. 48%) (P=0.009). FFR patients had less extensive disease as manifested by fewer native vessels with &gt;70% stenosis than non-FFR patients (1.0 [0.9] vs. 1.5 [1.0], P&lt;0.001) and less complex disease as assessed by the Duke jeopardy score (P&lt;0.001). After 5 years of follow-up, individuals who underwent FFR had less CV death/MI (89% vs. 84%; log-rank P=0.046). However, on Cox proportional hazards analysis, FFR was not independently associated with CV death/MI (HR 0.89; 95% CI: 0.60-0.98; P=0.58). Conclusion: ISCHEMIA patients randomized to INV strategy who underwent FFR had less complex and extensive coronary disease and, on unadjusted analysis, less CV death/MI. However, after adjustment for differences in baseline characteristics, FFR was not independently associated with CV death/MI.
Abstract 4147103: Role Of Inflammation in Coronary Microvascular Function in Acute Coronary Syndromes
Authors: Alvaro Gabaldon Badiola, Ana I Fernandez, Enrique Gutierrez, Ricardo Sanz, Irene Martin de Miguel, Francisco Fernandez Aviles, Marta Fernandez-Castillo, Jaime Elizaga, Rafael Correa, Javier Bermejo
Journal: Circulation (2024)

Introduction: CD4+ Th cells and related cytokines play a predominant role in the proinflammatory response in acute coronary syndrome (ACS). However, there is limited information on the relationship between inflammation and coronary microvascular dysfunction in ACS. Hypothesis: There is an interplay between inflammation and coronary microvascular disfunction in ACS. Methods: Coronary flow reserve as measured by Doppler flow velocity in response to adenosine (CFR) and in response to acetylcholine (endothelial CFR) was assessed in non-culprit arteries in patients with ACS. Correlation analyses with Th cell populations and plasma-related cytokines were performed. Results: A total of 26 patients diagnosed with ACS were studied (NCT03434483), with a median age of 55 years (IQR 19.8), and 96.2% were male. At presentation, 19.2% of patients had unstable angina, 42.3% had NSTEMI, and 38.5% had STEMI. There was a negative correlation between CFR (Figure 1) and Th1 cells (R -0.39, p = 0.047) and positive with IL-4 (R 0.5, p = 0.021). When analysing endothelial CFR (Figure 2), there was a positive correlation with Th17 cells (R 0.59, p = 0.016), Th1/Th17 cells (R 0.59, p = 0.015), MMP1 (R 0.6, p = 0.041), CCL2 (R 0.64, p = 0.024) and LTA (R 0.65, p = 0.022) cytokines and negative with CSF3 (R -0.61, p = 0.035). Conclusions: The study highlights the complex interactions between inflammation and coronary microvascular function in the setting of ACS. CFR seems to improve with lower levels of inflammation, but correlations with Th17 and Th1/Th17 seem to indicate the opposite in regards to endothelial CFR. The correlations with MMPs should be further explored as they are known to be directly involved in endothelial function.
Abstract 4147981: Enhanced Subclinical CAD Risk Prediction Using Lp(a): the BioHEART-CT Study
Authors: Sina Fathieh, Michael Patrick Gray, Stephen Vernon, Owen Tang, Stuart Grieve, Gemma Figtree
Journal: Circulation (2024)

Background: Lipoprotein(a) (Lp(a)) is now recognised as a key cardiovascular risk factor. Genetically determined and stable throughout adulthood, Lp(a) increases thrombotic risk and promotes atherosclerosis. Doubling Lp(a) levels raises cardiovascular disease risk by 22%. We aimed to evaluate the potential of Lp(a) to predict subclinical coronary artery disease in a well-characterised CCTA cohort, where early plaque detection may guide personalised treatment. Method and Results: 1,718 participants from the BioHEART-CT cohort were included in this analysis, who presented for a CCTA for suspected CAD without a prior history of myocardial injury or revascularisation between 2015 and 2021. CAD burden was assessed using coronary artery calcium scores and Gensini scores. Lp(a) levels were measured using ELISA. We evaluated the ability of Lp(a) to reclassify patients into correct CAD risk prediction categories: &lt;10% low risk, 10-30% moderate risk, and &gt;30% high risk. Logistic regression, adjusting for age, sex, hypertension, diabetes, hypercholesterolemia, and smoking status, revealed a net reclassification index (NRI) of 16% (p=0.001) and an integrated discrimination improvement (IDI) of 0.0046 (p=0.03), indicating accurate reclassification of one in 20 patients. In clinically actionable CAD (calcium score ≥100) cases, 26% were correctly reclassified from low to intermediate risk, 21% from intermediate to high risk, and only 2% were incorrectly reclassified. For non-clinically actionable CAD, 10% shifted from high to intermediate risk, 5% from intermediate to low risk, while 14% and 6% were misclassified into higher and intermediate-risk groups, respectively. Conclusion: Consideration of Lp(a) can potentially triage patients otherwise considered low risk for imaging to identify and treat atherosclerosis. It serves as an important screening biomarker with the potential to serve as an important non-invasive tool to identify vulnerable CAD patients who are currently underdiagnosed, such as patients without standard modifiable cardiovascular risk factors (SMuRFs).
Abstract Sa201: Effect of Spontaneous Gasping on Intraventricular Volume and Pressure during Untreated Ventricular Fibrillation
Authors: Pouria Pourzand, Bailey Kent, Mithun Suresh, Johanna Moore, Bayert Salverda, Anja Metzger, Nicolas Segond, Guillaume Debaty, Hamza Hai, Keith Lurie
Journal: Circulation (2024)

Background: Spontaneous gasping or agonal respiration during cardiac arrest is an auto-resuscitative reflex. Patients who gasp during cardiac arrest have better outcomes, regardless of the presenting rhythm. The physiological effects of gasping are similar to taking a deep breath: intrathoracic and intracranial pressure decrease, respiratory gas enters the lungs, venous blood refills the right ventricle (RV). Impedance threshold device (ITD) resistance to inspiration, with or without CPR, further reduces intrathoracic pressure. This study tested the hypothesis that gasping during untreated ventricular fibrillation (VF) would increase left ventricular (LV) and RV pressure and volume, and that ITD use would accentuate these effects. Method: 13 male and female pigs were anesthetized, intubated and mechanically ventilated. VF was induced and left untreated for 10 minutes. Hemodynamics, including biventricular pressure and volume loops using intracardiac conductance catheters were recorded during spontaneous gasping. An ITD, attached to the endotracheal tube, was used intermittently in each pig. Values (mean ± SE) were compared using the mixed-effects model, accounting for animal-to-animal variability and repeated measurements. Results: Baseline RV and LV stroke volumes (ml) were 52.2 ± 4.0 and 49.7 ± 6.9, respectively, before VF. A total of 84 gasps were recorded during untreated VF in all animals: 56 without and 28 with an ITD. There were 11.7 ± 1.0 gasps per pig starting 116.5 ± 6.4 seconds after VF. Gasping intensity followed a crescendo/decrescendo pattern with an initial negative inspiratory phase and a positive expiratory phase. ITD use during gasping significantly decreased in airway pressure (-11.0 ± 0.5 vs -1.8 ± 0.5, p&lt;0.01) versus no ITD. The intraventricular volumes and pressures (mmHg) generated during gasping increased significantly from no ITD to ITD use: RV volume 27.8 ± 3.5 vs 41.4 ± 3.8, p&lt;0.01; RV pressure 14.7 ± 2.2. vs 18.7 ± 2.3, p&lt;0.01, and LV volume 15.0 ± 2.5 vs 19.6 ± 2.8 p=0.053; LV pressure 19.3 ± 3.2 vs 25.8 ± 3.5, p&lt;0.01. Conclusion: Gasping during untreated VF generated RV and LV volumes and pressures of ~ 55% and 27% of pre-VF diastolic values, respectively, while using an ITD increased generated RV and LV volumes and pressures to ~ 85% and 36% of pre-VF diastolic values, respectively. These findings demonstrate the mechanism by which gasping enhances circulation and the clinical importance of this fundamental auto-reflex.
Abstract 4147592: Acute Pressor, Chronotropic and Adrenergic Effects of Adderall - A Randomized Double-Blind Placebo Controlled Crossover Study
Authors: Kiran Somers, Joshua Bock, Naima Covassin, Jan Bukartyk, Aiswarya Rajendran, Anna Svatikova
Journal: Circulation (2024)

Introduction: Adderall, the brand name for a combination of dextroamphetamine and amphetamine salts, is used to treat attention deficit disorder and narcolepsy, but is widely abused for improving cognitive function and alertness in absence of a medical indication. While little is known of its acute cardiovascular (CV) physiologic effects, Adderall has been linked to acute CV events (myocardial infarction, tachyarrhythmias, heart failure, Takotsubo cardiomyopathy and sudden death) and to long term CV consequences including hypertension and arterial disease. Aim: To examine the acute CV responses to Adderall in healthy subjects not on stimulant therapy in a randomized double-blind placebo-controlled crossover study. (CT.gov NCT02979327) Methods: Thirty subjects were randomized to 25 mg Adderall versus placebo. We measured supine resting blood pressure (BP), heart rate (HR), and plasma catecholamines, before and 3 hours after consuming Adderall or placebo. Results: Twenty-nine subjects (16 females; aged 25±5 yrs) completed both Adderall and placebo conditions, with a median of 10 days between visits. Systolic BP (SBP) increased from 112±10 mmHg to 127±11 mmHg after use of Adderall but was unchanged before vs after placebo drug intake (112±8 mmHg and 112±9 mmHg respectively; group by time interaction p&lt;0.01). Diastolic BP and mean BP increased by 6.8 mmHg and 8.5 mmHg respectively and HR increased by 7.3 beats/min with Adderall, but they did not change with placebo (p&lt;0.01). Plasma norepinephrine increased from 217±79 pg/ml before to 323±105 pg/ml after Adderall but was unchanged after placebo (p&lt;0.05) (Figure 1). Conclusions: Healthy subjects consuming a modest dose of Adderall manifest striking increases in BP, HR and sympathetic activation, even during supine rest. These findings may have important mechanistic implications for understanding acute CV events and long-term risk of CV disease associated with stimulant medications.
Abstract 4147427: Pulmonary Artery Distensibility in Pulmonary Artery Hypertension: Comparison of Cardiac Magnetic Resonance with Echocardiography
Authors: Marco Giacalone, Hoda Mombeini, Valentina Mercurio, Vivek Jani, Ryan Osgueritchian, Ami Shah, Stefan Zimmerman, Bharath Ambale Venkatesh, Stephen Mathai, Paul Hassoun, Monica Mukherjee
Journal: Circulation (2024)

Background: Right heart adaptation to emerging pulmonary arterial hypertension (PAH) largely determines outcomes. While numerous studies focus on ventricular remodeling, few explore the contribution of pulmonary artery (PA) stiffness indices across PAH subtypes. Research Questions and Aims: We assessed PA distensibility (PAD) in systemic sclerosis (SSc) patients with and without PAH compared with idiopathic pulmonary arterial hypertension (IPAH) using cardiac magnetic resonance imaging (CMR) and transthoracic echocardiography (TTE). We also assessed the intermodality agreement in PAD assessment. Methods: We included SSc and IPAH patients who underwent right heart catheterization (RHC), CMR, and TTE. PAD was calculated using CMR transaxial PA images and TTE parasternal short-axis PA view with measurement of systolic and diastolic diameters. The areas corresponding to these diameters were derived using the formula for the area of a circle (πr 2 ). PAD was computed as PA pulsatility over pulse pressure, with PA pulsatility being the percentage change in PA cross-sectional area between systole and diastole. Results: Of 45 SSc patients (34 with PAH, 11 without) and 16 IPAH patients, 46 had adequate image quality. Mean PA pressure by RHC was notably higher in IPAH cases than in those with SSc-PAH. PAD and PA pulsatility were lowest in the SSc-PAH group, followed by IPAH, and highest in the SSc without PAH group (p&lt;0.001). In PAH, PA pulsatility differed between SSc-PAH and IPAH. Figure 1 demonstrates a strong positive correlation (R=0.965) and substantial intermodality consistency (CCC=0.942). Agreement was stronger at lower values, with increased dispersion at higher values. Over 60 months, intermodality metrics of PAD and PA pulsatility predicted mortality. Kaplan-Meier analysis revealed that PA pulsatility greater than 10.5% significantly predicts better survival than less than 10.5%. Conclusion: We found diminished PAD in SSc-PAH than IPAH, despite lower PA pressures, predictive of mortality. We also demonstrate intermodality agreement supporting that TTE may be an alternative to CMR for assessing PAD.
Abstract 4147789: The Efficacy and Safety of Cardiac Myosin Inhibitors Versus Placebo in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy: A Meta-Analysis of Randomized Controlled Trials
Authors: Chidubem Ezenna, Meghna Joseph, Mrinal Murali Krishna, Favour Nelson, Gabriel Alugba, Ancy Jenil Franco, Prasana Ramesh, Uneza Khawaja, Andrew Goldsweig
Journal: Circulation (2024)

Introduction: Obstructive hypertrophic cardiomyopathy (oHCM) is a genetic disorder characterized by asymmetric myocardial hypertrophy, which can obstruct left ventricular outflow. Recently, myosin inhibitors have emerged as a novel therapeutic targeting cardiac muscle hypercontractility. Objective: To assess the efficacy and safety of myosin inhibitors mavacamten and aficamten in patients with oHCM. Methods: We systematically searched PubMed, Scopus, and Cochrane Central databases for studies comparing mavacamten or aficamten to placebo in patients with symptomatic oHCM. Outcomes included improvement in peak oxygen consumption (pVO2) and NYHA function≥1 class (NYHA-FC), change in Kansas City Cardiomyopathy Questionnaire (KCCQ), peak left ventricular outflow tract gradient at rest (rLVOT) and with Valsalva maneuver (vLVOT) and treatment-emergent and serious adverse events. Random effects models generated risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). Heterogeneity was assessed using I 2 statistics. Results: Search identified 5 randomized controlled trials including 767 patients (mavacamten 30.4%, aficamten 22.2%, placebo 47.4%) with mean follow-up of 22 weeks. Compared to placebo, myosin inhibitors were associated with improvement of ≥1 NYHA-FC (RR 2.33; 95%CI 1.92-2.82), rLVOT (MD -38.53; 95%CI [-46.06]-[-30.99]), vLVOT (MD -47.29; 95%CI [-58.03]-[-36.55]), pVO2 (MD 1.66; 95%CI 1.12-2.19), and KCCQ (MD 7.79; 95%CI 5.63-9.94) (Figure1). Other outcomes were similar with drug and placebo. Conclusion: Cardiac myosin inhibitors are an effective and safe short-term treatment for symptomatic oHCM.
Abstract 4147784: Computational Fluid Dynamics is Key Predictors of Adverse Events in Single Ventricle Patients After the Fontan
Authors: Zhenglun Wei, Fatemeh Salargarna, Jessica Murawsky, Biao Si, Joshua Frechette, Allen Carter, Jian Zou, Ajit Yoganathan, Mark Fogel
Journal: Circulation (2024)

Introduction: Single ventricle patients following Fontan surgery may experience significant adverse outcomes. Hemodynamic metrics derived from image-based computational fluid dynamics (CFD) analysis could potentially serve as predictors. Hypothesis: CFD-based measures can prognosticate the consequences of Fontan surgery. Methods: This study randomly selected 217 Fontan patients who presented for cardiac magnetic resonance (CMR) from 2004-present obtaining anatomy and flows in the cavae and pulmonary arteries to obtain CFD. Hemodynamic metrics were indexed power loss (iPL, unitless) and resistance to flow in the Fontan connection (R TCPC , in WU). Recorded adverse events (AEs) included death, transplantation, cardiac arrest, admission to the cardiac intensive care unit, pleural effusion, catheterization, pacemaker implantation, protein-losing enteropathy, plastic bronchitis, liver fibrosis and cirrhosis, heart failure, and sustained ventricular tachycardia (VT). Independent two-sample Student's t-tests or Mann-Whitney tests were conducted depending on the normality of the data. Statistical significance was set at p &lt; 0.05. Results: Age at initial CMR was 12.9 ± 8.2 years, with 37 patients undergoing a second CMR at 16.8 ± 8.1 years. Follow-up occurred 5.1 ± 2.6 years after the initial CMR. The number of patients who experienced an outcome is in Table 1. In the cross-sectional study (n = 217, Table 2), both iPL and R TCPC were significantly correlated with subsequent occurrence of AEs. Higher iPL was significantly associated with liver fibrosis (p = 0.027) and cirrhosis (p = 0.042) and showed a borderline statistical significance for death (p = 0.055). Higher R TCPC predicted liver cirrhosis (p = 0.043) and death (p = 0.045), with borderline significance for liver fibrosis (p = 0.058). The longitudinal study (n = 36, Table 3) demonstrated that changes in R TCPC predicted death (p = 0.029), while changes in iPL were borderline significant (p = 0.058). Additionally, changes in R TCPC were also significantly correlated with sustained VT. Conclusion: CFD-derived hemodynamics from CMR demonstrated promise as an important predictor of adverse events in single ventricle patients after Fontan. A larger prospective trial is warranted.