tbuckley/cabot-search huggingface dataset:
Abstract 4144961: Validation of Right Ventricle and Pulmonary Artery Decoupling via Non-Invasive and Invasive Measurements in Pulmonary Arterial Hypertension: Significance and Considerations for Early Detection and Prognostic Stratification
Authors: Takahiro Hiraide, Hikaru Tsuruta, Mitsushige Murata, Masaki Ieda
Journal: Circulation (2024)

Backgrounds: The ratio of tricuspid annular plane systolic excursion over the estimated pulmonary artery systolic pressure (TAPSE/PASP) has shown as a parameter of coupling between right ventricle and pulmonary artery. Despite its importance, the accuracy of estimating PASP in echocardiography and the diagnostic/prognostic value of TAPSE/PASP are not fully understood. Methods: We examined 697 pairs of right heart catheterization and echocardiography performed in 264 patients who were suspected to have pulmonary arterial hypertension (PAH). We excluded the data of echocardiogram with no TR (n = 6). The correlation of PASP measured by right heart catheterization and echocardiography was analyzed according to the severity of tricuspid regurgitation (TR). The accuracies of predicting the presence of PAH by TAPSE/PASP were examined by receiver operating characteristic (ROC) curve analysis. The severity of TAPSE/PASP was categorized in three groups according to the current guideline (low: &lt; 0.19, intermediate: 0.19 - 0.31, high: &gt; 0.31 mm/mmHg), and the association between TAPSE/PASP and composite prognosis of cardiovascular death or lung transplantation was evaluated by Kaplan-Meier analysis. Results: At baseline, median age was 57 [interquartile range: 42, 71], 188 (71.2%) of the patients were female, median TRPG was 50.7 [35.0, 69.3] mmHg, median TAPSE was 18.0 [14.9, 23.0] mm, and median mean PAP was 34 [21, 46] mmHg. Trivial TR was identified in 159 (23.0%) echocardiography, and PASP was likely to be underestimated in patients with trivial TR (panel A). TAPSE/sPAP was inversely correlated with pulmonary vascular resistance (panel B), and ROC curve analysis demonstrated that TAPSE/PASP 0.55 was the best threshold in predicting the presence of PAH, but the threshold was higher in trivial TR (panel C). The Kaplan-Meier analysis demonstrated that patients whose TAPSE/PASP were under 0.19 mm/mmHg had significant worse prognosis in contemporary intensive treatment of pulmonary vasodilators (panel D). Conclusions: PASP measured by echocardiography is an accurate noninvasive parameter to estimate the hemodynamics and prognosis in patients with PAH. Since the trivial TR may underestimate the PASP, presence of other echocardiographic signs of PAH should be evaluated especially in patients with trivial TR.
Abstract 4144972: Predictors of cardiovascular disease risk and total mortality: Findings from the UK Biobank.
Authors: Ebiambu Ondoh Agwara, Sarah Armes, Marjorie Lima Do Vale, Christine Delon, Ramya Rajaram, Mayara De Paula, Rajna Gulobic, SUMANTRA RAY
Journal: Circulation (2024)

Background: Cardiovascular disease (CVD) continues to remain a major health challenge with several physiological and lifestyle markers associated with its incidence, burden and mortality. Purpose: We aimed to investigate diet and other lifestyle variables in combination with CVD risk markers (clinical and laboratory measurements) to estimate the risk of CVD events, all-cause Mortality, and survival rates over an 18-year period. Methods: Data from the UK biobank was utilised. Participants recruited between 2006 and 2010. Variables included predictor (sex, age, smoking history, and Townsend deprivation), Clinical (BMI, SBP, DBP, HBA1C, triglycerides, TC/HDL ratio, and total cholesterol (TC)) and behavioural (diet, physical activity). Deaths were coded using the ICD, 10th revision. COX proportional hazard models used to analyse each outcome for every predictor variable and models adjusted for confounders. Survival analysis was done with logistic regression models. Outcomes included all-cause mortality and incidence of fatal cardiovascular disease. Results: Over 502,621participants aged between 40-69 years with 54.4% males. 4.6% developed CVDs. High (&gt;8) and low (&lt;7) sleep hours, High BMI, HBA1C, SBP, triglycerides and TC/HDL had a higher CVD incidence risk. Age, Sex, smoking, and Townsend deprivation were independent predictors of mortality with sex and smoking carrying the highest risk. Vegetarians and participants on combined special diets had a lower total mortality. Physical activity of 2-4 hrs and 4-6 hrs weekly had lower mortality compared to no physical activity. However, light or vigorous physical activity had no significant effect on total mortality. Similarly, individuals with no metabolic equivalent task (MET) had an increased mortality compared to those with 12-14 hrs, 14-16hrs, and 16-84hrs MET. High BMI, triglycerides, HBA1C and TC/HDL ratio were associated with significantly decreased survival rates while High HDL and high TC was associated with increased survival rates. Conclusion: Lifestyle factors including physical activity, sleep, and diets were identified as important predictors of all-cause mortality and CVD risk events. The findings further strengthen the evidence on the role of other known modifiable and non-modifiable factors in predicting CVD incidence risk and total mortality. The identified predictors would be useful in the development of risk scoring systems which incorporate lifestyle factors not factored into most CVD risk prediction models.
Abstract 4145126: Catheter Ablation of Atrial Arrhythmias in Patients with Cardiac Amyloidosis
Authors: Brian Diep, Jakrin Kewcharoen, Jalaj Garg
Journal: Circulation (2024)

Background: Cardiac amyloidosis is an infiltrative disease that is associated with various atrial arrhythmias (AA). Data on the efficacy and safety of catheter ablation (CA) in this population is scarce, thus, we evaluated it in patients with cardiac amyloidosis. Methods: We performed a systematic review by searching for studies in all major databases. Random effect model was used to assess pooled incidence of outcomes with a 95% confidence interval (CI). Outcomes included 1) Freedom from AA; 2) Procedural complications (including pericardial effusion, cardiogenic shock and major bleeding); 3) Stroke during follow-up; 4) Cardiovascular hospitalization; 5) All-cause mortality. Results: 7 studies were included in the meta-analysis comprised 376 patients (mean age 71.24.9, 71% male, 95% atrial fibrillation (AF), 2% atrial flutter (AFL), &lt;1% atrial tachycardia (AT), &lt;1% AF/AFL, 3% AF/AT, 86% transthyretin amyloid). During a mean follow-up period of 29.6 months, freedom from AA was 42% (CI: 22-62%). Procedural complications, stroke during follow-up, cardiovascular hospitalization and all-cause mortality occurred in 3% (CI: 0-9%), 1% (CI: 0-2%), 10% (CI: 2-18%) and 17% (CI: 7-27), respectively (Figure). Conclusions: CA for AA in patients with cardiac amyloidosis is safe, despite high recurrence rates. Due to significant comorbidities in these patients, further studies are needed to evaluate for optimal treatment strategy for AA in patient with cardiac amyloidosis.
Abstract 4144863: Impact of Phone Outreach and In-Person Education on Blood Pressure Control in Black Patients with Severe Hypertension at a Federally Qualified Health Center (FQHC)
Authors: Perisa Ashar, Jada Allen, Rohan Gupta, Huda Haque, Camryn Johnson, Caroline Metz, Jennifer Nguyen, Ashna Sai, Anna Tharakan, Eric Wang, Velda Wang, Elliot Yoon, Marcie Burnette, Holly Biola, Bradi Granger
Journal: Circulation (2024)

Introduction: Black Americans are 30% more likely to have hypertension (HTN), and they experience 4-5 times greater HTN-related mortality as compared to White Americans. Despite the higher risk, Black patients have lower blood pressure (BP) control than White patients. These disparities can be addressed through improved engagement and self-monitoring of BP (SMBP). Hypothesis: We hypothesize that telephonic outreach with in-person educational interventions will promote BP control in Black patients with HTN. Methods: We conducted a pre-post single cohort study targeting minority patients with uncontrolled HTN (systolic BP [SBP] &gt; 160 mmHg and/or diastolic BP [DBP] &gt; 100 mmHg) in an FQHC. Trained students conducted telephone outreach to bring HTN awareness to 291 patients. In-person classes provided education about lifestyle modifications (exercise, nutrition, and medication compliance), distributed BP cuffs, and taught patients SMBP. Patient engagement, interest in classes, BP recordings before and after telephonic outreach, and in-person class attendance were analyzed. Results: From 291 patients, 149 (51.2%) were reached (Figure 1). Among patients who engaged with the entire call (n=137, 91.9%), 71 (77.2%) expressed interest in attending classes. Significant reductions in SBP (170.47 mmHg to 139.94 mmHg, p&lt;0.001) and DBP (97.15 mmHg to 83.21 mmHg, p&lt;0.001) were observed post-telephonic outreach (n=34) (Figure 2). Of the 24 patients who attended in-person classes, 12 (50%) responded to telephonic outreach and demonstrated increased continuity with follow-up primary care visits. During their first class, 18 (75%) patients did not own a BP cuff. Conclusions: Telephonic engagement is associated with improved BP and greater class attendance, but barriers to in-person attendance remain. Providing BP monitors and integrating digital education resources could improve engagement and outcomes for high-risk Black patients.
Abstract 4144882: Loss of function polymorphism in the ecto-5’-nucleotidase (NT5E) gene increases atherosclerotic burden.
Authors: Ana Roman, Lauren Dittrick, Kyle Gordon, Oscar Bermeo Blanco, Samuel Watson, Channabasavaiah Gurumurthy, Quinn Wells, Roman Covarrubias, Rolen Quadros, Richard Gumina
Journal: Circulation (2024)

Objective: To elucidate the molecular mechanisms by which CD73 variants contribute to inflammation and atherosclerosis in humans. Approach and Results: To explore this knowledge gap, we conducted phenotype-wide association analysis (PheWAS) in a cohort of 25,000 patients to identify ASCVD-associated variants in the NT5E (CD73) gene in a non-biased manner. PheWAS analysis of coding variants identified that the rs200648774 single nucleotide polymorphisms in ecto-5’-nucleotidase (NT5E; CD73) that was associated with atherosclerosis (ICD-9; 440.x codes) in this cohort. The SNP rs200648774 (C--&gt;T; MAF 0.000188) results in an Arginine (R) to Cysteine (C) substitution at amino acid 354 within the active site of CD73 (OR: 10.18, SE: 1.1; P=0.035). This Arginine residue is evolutionarily conserved across species. The variant protein is expressed but displays a loss of function (LOF; CD73 Cys354 variant). To examine the impact of the CD73 Cys354 variant , we generated a murine model using E fficient a dditions with s sDNA i nserts-CRISPR (Easi-CRISPR) gene editing. CD73-Arg354/Arg354 (cd73 wt/wt ) and CD73-Cys354/Cys354 (cd73 Δ/Δ ) mice in an Ldlr -/- background were placed on HFD for 12 weeks then sacrificed for quantification of aortic root atherosclerosis. Representative images of oil red O staining of aortic valve from CD73-Arg354/Arg354- Ldlr -/- (cd73 wt/wt , Ldlr -/- ) mice (Fig. A; Bar= 100 um) and CD73-Cys354/Cys354 Ldlr -/- (cd73 Δ/Δ , Ldlr -/- ) mice (Fig. B; Bar= 100 um). Quantified area of atherosclerosis in CD73-Cys354/Cys354 (cd73 Δ/Δ ) aortic roots were significantly higher in CD73-Cys354/Cys354 (cd73 Δ/Δ ) than in CD73-Arg354/Arg354 (cd73 wt/wt ) (Fig. C; p=0.0096). The Percentage of Oil Red O staining in aortic root atherosclerotic lesions was also significantly higher in CD73-Cys354/Cys354 (cd73 Δ/Δ ) aortic roots compared to CD73-Arg354/Arg354 (cd73 wt/wt ) aortic roots. Together these data demonstrate that the rs200648774 single nucleotide polymorphisms resulting in cysteine substitution for arginine in the active site of CD73 results in a loss of CD73 function that also associates with increased atherosclerosis in genetically susceptible mice . Conclusion: The LOF rs200648774 single nucleotide polymorphisms associates with atherosclerosis in humans and generation of the CD73-Cys354/Cys354 polymorphism in Ldlr -/- mice results in increased HFD induced atherosclerosis
Abstract 4145162: Empagliflozin Effect on Left Cardiac Parameters in Acute Coronary Syndrome: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Authors: Ghaith Eljadid, Mohamed Rakab, Ahmed Mansour, Yasmeen Abdelglel Mohamed, Ahmed Abbas, Nereen Almosilhy, Noura Abdrabou, Ameerh dana Sabe alerab, Ahmed Khaled, Elarbi Goufa, Ahmed Elbataa, Heba Aboeldahab, Ahmed A. Ibrahim, Ahmed gaber elsayed elsayed emara
Journal: Circulation (2024)

Background: Acute coronary syndrome (ACS) poses a significant global health burden despite advancements in its management. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, primarily used in type 2 diabetes mellitus (T2DM), have gained recent consideration as potential agents for ACS management due to their cardiovascular benefits beyond glycemic control. This study aimed to assess the effects of empagliflozin on left cardiac parameters in ACS patients. Methods: PubMed, Cochrane, Scopus, and Web of Science were searched thoroughly to identify relevant randomized controlled trials (RCTs) until June 1st, 2024. Continuous data were pooled using mean difference (MD) with a 95% confidence interval (CI) using R (Version 4.3). Results: Four RCTs involving 701 patients were included. Compared to placebo, empagliflozin significantly reduced left ventricular end-systolic volume index (LVESVi) (MD: -2.38, 95% CI: -3.95 to -0.80, p = 0.0032), left ventricular mass index (LVMi) (MD: -2.76, 95% CI: -4.95 to -0.56, p = 0.0137), and left ventricular filling pressure (E/e') (MD: -0.59, 95% CI: -1.07 to -0.10, p = 0.0189). However, empagliflozin treatment did not yield a statistically significant change in left ventricular ejection fraction (LVEF) (MD: 1.21, 95% CI: -0.05 to 2.48, p = 0.0603), nor a significant change in left ventricular end-diastolic volume (LVEDV) (MD: -4.49, 95% CI: -14.24 to 5.26, p = 0.37), left ventricular end-systolic volume (LVESV) (MD: -5.19, 95% CI: -10.77 to 0.39, p = 0.0682), and left ventricular end-diastolic volume index (LVEDVi) (MD: -2.20, 95% CI: -4.59 to 0.19, p = 0.0718). Conclusion: Empagliflozin provides favorable effects on left cardiac structural parameters in ACS patients, as it was associated with reduced LVESVi, LVMi, and E/e'. This suggests a potential role for SGLT2 inhibitors as adjunctive therapy in ACS management, warranting further investigation into their mechanisms and long-term clinical outcomes.
Abstract 4144815: Natriuretic peptide-guided therapy in acute decompensated heart failure: An updated systematic review and meta-analysis
Authors: Luciana Gioli-Pereira, Eric Katsuyama, Camila Campos Grisa Padovese, Silvana Ribeiro Papp, Rafael Hortêncio Melo, Edielle de Sant Anna Melo
Journal: Circulation (2024)

Background: Natriuretic peptides (NP) are frequently employed in diagnosing heart failure (HF); however, their effectiveness in guiding HF treatment lacks sufficient evidence. To address this gap, we conducted an updated meta-analysis assessing the efficacy of NP-guided therapy versus usual care in decompensated HF. Methods: PubMed, Embase and Cochrane database were searched for randomized controlled trials (RCTs) that compared NP-guided treatment to usual care for patients with acute decompensated heart failure. The reported outcomes were (1) all-cause mortality; (2) cardiovascular death; and a (3) composite of all-cause mortality and HF hospitalizations. Heterogeneity was examined with I 2 statistics. A random-effects model was used for outcomes with high heterogeneity. Statistical analysis was done using R Studio 4.3.2. Results: We included 10 RCTs with 4122 patients, of whom 2072 (50.3%) underwent NP-guided treatment. Mean follow-up was 14.8 months. All-cause mortality (HR 1.03; 95% CI 0.81-1.32; p=0.79; figure 1A), cardiovascular death (HR 1.33; 95% CI 0.72-2.47; p=0.36; figure 1B), and the composite outcome of HF hospitalization or cardiovascular death (HR 0.92; 95% CI 0.77-1.11; p=0.4; figure 1C) were not significantly different between groups. Conclusion: These findings suggest that NP-guided therapy does not reduce mortality and heart failure readmissions in the management of patients with acute decompensated heart failure.
Abstract 4145174: Impact of chronic reductive stress on myocardial proteome turnover: Insights into proteotoxicity and predictive cardiac remodeling
Authors: Rajasekaran Namakkal-Soorappan, DING WANG, CHUN NG, Asokan Devarajan, Anil Kumar Challa, Peipei Ping
Journal: Circulation (2024)

Background: Protein half-life and turnover are crucial for cellular function, especially under basal and stress conditions, often contributing to proteinopathies. While the impact of oxidative stress (OxS) on proteostasis is well-documented, the role of reductive stress, an overabundance of antioxidant status, in proteotoxic cardiac disease remains elusive. Hypothesis: Tested whether chronic reductive stress (cRS) impairs protein turnover and induce proteotoxic cardiac disease. Methods: In transgenic mice expressing constitutively active Nrf2 (caNrf2-TG) and non-transgenic controls (n=6/gp.), we examined the half-life and turnover rates of the myocardial proteome using D2O labeling and mass spectrometry. Results: We observed significant changes in the half-life of over 1,700 proteins, with approximately 1,200 proteins exhibiting increased half-life at 3 months, despite no noticeable defects in cardiac structure and function. Under OxS induced by isoproterenol (ISO), about 700 proteins showed reduced half-life, underscoring distinct regulatory mechanisms in protein turnover between cRS and OxS. Proteins with altered half-lives were involved in key cellular functions, including metabolism, signal transduction, immune response, transport, and cell cycle regulation under cRS, revealing novel targets undetected in an OxS context. Notably, distinct positive adaptive compensatory (59; p&lt;0.05) and maladaptive pathologic (58; p&lt;0.05) responses were observed, resulting in unusual protein stabilization and aggregation, leading to proteotoxic stress under cRS. Comparing transcript levels and protein half-life/turnover (HL/TnO) revealed non-linear metrics for subsets of proteins under cRS. Furthermore, bioinformatic predictions identified potential post-translational modification sites in critical proteins with extended half-lives, correlating with the onset of myocardial remodeling in cRS hearts at 3 months, as indicated by altered Tie index and irregular vector velocities of regional wall motions. Conclusion: Our findings highlight the importance of prolonged protein half-life and reduced turnover, along with unchanged or decreased transcription, as predictive markers for proteotoxic cardiac disease.
Abstract 4144881: Peak METs vs. Peak VO2: When is it not predictive?
Authors: Kalyan Chaliki, Anubhuti Sharma, Arundhati Sharma, Taylor Viggiano, Claire Yee, Satyajit Reddy
Journal: Circulation (2024)

Introduction: Metabolic equivalents (METs), a measure of energy use during a specified exercise intensity, and volume of oxygen consumed (VO2) are key measurements in cardiopulmonary exercise tests (CPETs). METs are traditionally converted to VO2 via multiplying METs by 3.5 ml/kg/min when VO2 data is not available, due to the fact that the latter requires more-expensive, accurate measurements of volume of inspired and expired oxygen and CO2. However, it is unclear which populations have significant variation between peak METs and peak VO2. Research Question: In a general cardiology population, do older women have a weaker relationship between peak METs and peak VO2? Methods: We present a retrospective study analyzing the relationship of peak METs and peak VO2 achieved on a CPET. Patients presenting to the cardiology clinic who received a CPET from 2017-2022 were included. Patients with severe valvular dysfunction, congenital heart disease, prior coronary artery bypass grafting, or ejection fraction &lt; 50% were removed to limit confounding. A Spearman correlation coefficient was calculated for the whole sample comparing peak METs and peak VO2. Subsequently, a subgroup of women age 65 or greater were compared to the general sample by a fisher’s z transformation. Results: 1907 patients were included. There was a strong positive correlation between peak VO2 and peak METs in the whole sample (r(1860) = 0.914), p&lt;0,001), shown in Figure 1. Women age 65 or greater had a weaker correlation (r(190)=0.808, p&lt;0.0001) compared to the those who were not (r(1668) = 0.915, p&lt;0.0001; z = -5.656, p&lt;0.001), shown in Figure 2. Conclusions: Peak METs and peak VO2 have an extremely strong positive correlation in a general cardiology population. However, these relationships weaken for women age 65 or greater. METs are an accurate, cost-effective proxy measurement of VO2 in a general population, however may lack reliability for certain demographics.
Abstract 4144782: Identifying Factors Influencing Response to Dual Antiplatelet Therapy in Non-Cardioembolic Ischemic Stroke and Transient Ischemic Attack: A Meta-analysis of Randomized Controlled Trials
Authors: Kuan Yu Chi, Zafer Akman, Pei Lun Lee, Pawel Borkowski, Ishmum Chowdhury, Junmin Song, Yu Chang, Laura Romero Acero, Michele Nanna, MD, FACC, Michael Nanna
Journal: Circulation (2024)

Background: While dual antiplatelet therapy (DAPT) has been shown to significantly decrease recurrent stroke in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of non-cardioembolic origin, it comes with a substantial increase in the risk of bleeding. Research Question: Do all patients with non-cardioembolic, mild ischemic stroke/high-risk TIA derive benefits from DAPT for secondary prevention? Aims: To identify patients who derive attenuated benefit from DAPT to avoid excessive bleeding risk. Methods: We searched 6 databases from inception to May 10, 2024 to identify randomized-controlled trials (RCTs) comparing short-term DAPT (up to 3 months) with aspirin for secondary prevention of non-cardioembolic ischemic stroke or TIA. The primary efficacy outcome was major adverse cardiac and cerebrovascular events (MACCE), a composite of any stroke, myocardial infarction, and cardiovascular (CV) death, with prespecified subgroups based on participants’ pre-stroke treatment with statins and antiplatelet agents. Secondary efficacy outcomes comprised of recurrent ischemic events and hemorrhagic stroke. Safety outcomes included major bleeding, CV mortality, and all-cause mortality. A random-effects meta-analysis was performed using restricted maximum likelihood method. Results: There were 5 RCTs including 27,559 patients. In the unselected population, DAPT significantly reduced MACCE (RR, 0.78; 95% CI, 0.71 to 0.85; I 2 = 0%; Figure 1A), compared to aspirin. However, patients with baseline statin (RR, 0.93; 95% CI, 0.73 to 1.17; I 2 = 0%; Figure 1A) or antiplatelet (RR, 0.91; 95% CI, 0.69 to 1.21; I 2 = 0%; Figure 1A) before index events did not derive benefits from DAPT. While DAPT led to significantly lower recurrent ischemic stroke (RR, 0.74; 95% CI, 0.68 to 0.81; I 2 = 0%; Figure 1B), it resulted in a significantly higher risk of hemorrhagic stroke, major bleeding, and intracerebral hemorrhage, compared to aspirin (Figure 1B). Moreover, the use of DAPT trended toward an increased risk of all-cause and CV mortality (Figure 1B). Conclusions: Patients with baseline statin/antiplatelts use may not derive the same benefits from DAPT for secondary prevention of non-cardioembolic ischemic stroke or TIA.