tbuckley/cabot-search huggingface dataset:
Abstract 12740: Efficacy and Safety of Empagliflozin in Acute Heart Failure: A Systematic Review and Meta-Analysis
Authors: Muhammad Adil Afzal, Muhammad Abdullah, Noman Khalid, Rovena Collins, Taulant Gashi, Mubariz Hassan, Ata Ul Haiy, Sherif Elkattawy, Patrick Michael, Rahul Vasudev, fayez shamoon
Journal: Circulation (2023)

Introduction: Acute heart failure (AHF) significantly burdens healthcare systems, leading to hospitalizations, morbidity, and mortality in older adults. Among patients suffering from chronic heart failure, empagliflozin, which is a sodium-glucose cotransporter-2 (SGLT-2) inhibitor, has shown positive cardiovascular effects. While several studies have investigated SGLT-2 inhibitor use in hospitalized AHF patients, there is a lack of meta-analysis specifically focused on empagliflozin. To ascertain the efficacy and safety of empagliflozin in AHF, the following systematic review plus meta-analysis was conducted. Methods: We comprehensively searched Cochrane, Clinicaltrials.gov, and MEDLINE databases. After title, abstract, and full-text screening, the data discussing relevant safety and efficacy outcomes of empagliflozin were extracted, and a random-effects meta-analysis odds ratio was calculated. We conducted a sensitivity analysis by removing the post-hoc study. Results: We retrieved 852 documents after initial database searches, and after the screening, 3 RCTs were included with 824 participants. Empagliflozin significantly reduced the odds of all-cause mortality (OR: 0.47, 95%CI: 0.29-0.78, p=0.004) and cardiovascular death (OR: 0.56, 95%CI: 0.38-0.82, p=0.003) when compared to placebo. Furthermore, empagliflozin demonstrated a lower serious adverse event risk (OR: 0.62, 95% CI: 0.44-0.87, p=0.005) without exacerbating adverse drug effects such as acute kidney injury, diabetic ketoacidosis, hypotension, and urinary tract infections significantly. Sensitivity analysis confirmed these findings. Conclusion: Our study suggests that empagliflozin holds promise in reducing cardiovascular and all-cause mortality in AHF patients. However, its impact on rehospitalizations remains uncertain. Larger and more diverse clinical trials are warranted to establish further the role of empagliflozin in managing heart failure.
Abstract 12908: Non-Fatal Trial Endpoints of Drug Interventions in Heart Failure
Authors: Vagner Raso
Journal: Circulation (2023)

Introduction: The Food and Drug Administration (FDA) provides guidance on the use of endpoints for drug approvals in heart failure (HF). Hypothesis: The aim of this study was to systematically review whether clinical studies in HF report the FDA recommendations for endpoints. Methods: All studies targeting HF available on the clinical trials platform from the National Library of Medicine were analyzed. The FDA recommends a decrease in mortality as the primary efficacy endpoint and an increase in survival as the safety endpoint. Others include single or composite scores of hospitalizations, biomarkers, or symptoms and/or physical function. Results: Trials (n=4,978) were narrowed down to 1,299 (26%) studies with an active, but not recruiting, enrolling by invitations, not yet recruiting, and recruiting statuses. Only 132 (3%) studies using intervention with drugs reported endpoints. Up to 7,200 participants were randomly (n=95, 72%) assigned to parallel designs (n=81, 61%) followed by single group (n=19, 14%) or crossover designs (n=18, 14%) with open label (n=48, 36%) or quadruple masking methods (n=29, 22%). Interventions tested sodium-glucose co-transporter 2 (n=21, 16%) and angiotensin receptor-neprilysin inhibitors (n=13, 10%). Dapagliflozin (n=8, 8%), Sacubitril and Valsartan (n=6, 6%) followed by Levosimendan, Metformin, or Warfarin (n=3, 3%) were compared to placebo (n=51, 53%). Equivalence trials (n=35, 27%) analyzed Sacubitril and Valsartan (n=5, 14%), Dapagliflozin, Beta-hydroxybutyrate Ester, or Sacubitril and Valsartan with Para-aminohippurate, Lohexol, and Aprepitant (n=2, 6%). Most studies (n=55, 42%) assessed endpoints related to symptoms and/or physical function. Other endpoints included cardiac function (n=24, 18%) and biomarkers (n=19, 14%) followed by mortality and survival (n=18, 14%) or hospitalization (n=5, 4%). Conclusions: Most studies assessed symptoms, physical function, cardiac function, or biomarkers for primary endpoints. They have included non-fatal endpoints such as patient-reported outcomes or objective indicators likely due to the increasing number of patients with worsening heart failure in outpatient settings.
Abstract 12849: Assessing Cardiovascular Toxicity in Cancer Treatment: Validation of the Heart Failure Association and International Cardio-Oncology Society Tool Using Prospective Registry Data
Authors: Tatsuhiro Shibata, Shoichiro Nohara, Nagisa Morikawa, Kodai Shibao, Yoshihiro Fukumoto
Journal: Circulation (2023)

Introduction: Cancer treatment-related cardiovascular toxicity (CTR-CVT) is a growing concern in patients undergoing anticancer therapy. The Heart Failure Association (HFA) and International Cardio-Oncology Society (ICOS) risk assessment tools have been proposed for the baseline cardiovascular (CV) risk stratification of patients with cancer. This study examined the incidence of adverse CV events associated with cancer treatment in clinical practice, also using the HFA-ICOS risk assessment tool. Methods: This single-center, prospective, observational study was conducted at Kurume University Hospital between October 2016 and August 2021 in patients aged ≥20 years with hematologic malignancies or breast cancer who were receiving anticancer agents. CV assessments were performed at enrollment and every 6 months until February 2022, with additional assessments for suspected CV adverse events. The primary endpoint was adverse CV event as defined by Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade ≥2, and the secondary endpoints were all-cause and CV death. Results: Of the enrolled 486 patients, adverse CV events occurred in 24.5% of patients with leukemia, 15.8% of patients with malignant lymphoma, 38.1% of patients with multiple myeloma, and 18.0% of patients with breast cancer, respectively. Kaplan-Meier curves of the primary endpoint and heart failure (HF)/ left ventricular (LV) dysfunction stratified by HFA-ICOS risk assessment group have shown the significant worse events in high/very high-risk group, in which the hazard ratios in the high/very high-risk group compared to the low-risk group were 2.34 (95% CI 1.48-3.71, p&lt;0.001) in the primary endpoint and 3.57 (95% CI 1.70-7.51, p&lt;0.001) in HF/LV dysfunction. There was no significant difference in the event risk between the low- and moderate-risk groups. CV death occurred in 4 patients (0.8 %) during follow-up. Conclusions: This study showed that 16-38% of patients with hematologic malignancies and breast cancer developed CTR-CVT during follow-up, in which high/very high-risk patients were well predicted by the HFA-ICOS risk assessment tool. The monitoring and managing CV risk factors are essential for safe cancer therapy.
Abstract 14020: Five-Year Trends in Risk Factors for Cardiovascular Disease Among Adolescents in the United States
Authors: Ali Hasan, Kamleshun Ramphul, Raheel Ahmed, Muzammil Farhan, Azeem Hassan, rashmitha dachepally, Murad Almasri, Hasan Ahmad, Caleb Carver, Mohammad Saddam Jeelani, Yumna Jamil, Maham Bilal, Javed Ahmad, Rahat A Memon, Hemamalini Sakthivel
Journal: Circulation (2023)

Introduction: Cardiovascular disease is the leading cause of death in the United States (US) and worldwide. Past studies have demonstrated a rise in sedentary life-style among adolescents. We aim to provide an up-to-date representation of the prevalence of multiple cardiovascular risk factors amongst adolescents in the US. Methods: We queried hospitalization records of adolescents of ages 10-19 years (inclusive) via the 2016-2020 National Inpatient Sample, a set of de-identified records provided by HCUP, AHRQ and partners. The trends of several risk factors were estimated (per 100,000 hospitalization) via linear-by-linear analysis as per past studies of the database. Results: Our study found an increasing trend in prediabetes (41 per 100,000 in 2016 to gradually reach 309 per 100,000 in 2020, ptrend&lt;0.01), hypertension (2334 per 100,000 in 2016 to reach 2756 per 100,000 in 2020, ptrend&lt;0.01), diabetes (5119per 100,000 in 2016 to reach 5733 per 100,000 in 2020, ptrend&lt;0.01), obesity (6153 per 100,000 in 2016 to reach 8221 per 100,000 in 2020, ptrend&lt;0.01), smoking (8166 per 100,000 in 2016 to reach 9117 per 100,000 in 2020, ptrend&lt;0.01), and family history of ischemic heart disease or cardiovascular disease (1687 per 100,000 in 2016 to reach 1922 per 100,000 in 2020, ptrend&lt;0.01, ptrend&lt;0.01) (Figure 1). In addition, the incidence of acute myocardial infarction (AMI) rose from 34 per 100,000 in 2016 to reach 68 per 100,000 in 2020 (ptrend&lt;0.01). A similar rise in events of acute ischemic stroke (AIS) was seen with 123 cases per 100,000 reported in 2016 and this increased to 156 per 100,000 in 2020 (ptrend&lt;0.01) (Figure 1). Conclusion: There is an alarming rise in various risk factors that can lead to future cardiovascular disease among adolescents. Furthermore, the incidences of AMI and AIS among adolescents are on the rise. Stronger health-related sensitization campaigns promoting healthier life-style should be mooted.
Abstract 13715: Catheter-Based Therapies in High-Risk Pulmonary Embolism: Outcomes From a Tertiary Referral Center
Authors: Amine Al Soueidy, Gregory Miller, Shawana Hussain, jean-sebastien rachoin, Krystal Hunter, Elias A Iliadis
Journal: Circulation (2023)

Introduction: Prompt and effective treatment of pulmonary embolism (PE) is essential to prevent morbidity and mortality. We aim to evaluate and compare the effectiveness of two FDA-approved catheter-based therapies (CBT) for acute high-risk PE: ultrasound-assisted catheter-directed thrombolysis EKOS (EKOS Corporation, Bothell, WA) and Penumbra Indigo aspiration thrombectomy (Penumbra Inc., Alameda, CA, USA). Methods: Patients with acute high-risk submassive or massive PE who underwent CBTs between 09/2014 and 08/2022 at our institution were identified. The primary efficacy outcome was the change in the echocardiographic RV/LV diameter ratio within 48 to 72h of procedure. Results: A total of 189 patients underwent EKOS (n=119) or Penumbra (n=70) for submassive (n=175) and massive (n=14) PE (Table). Both groups had similar demographics and clinical characteristics except for prior DVT. Mean age was 60.6±14.3 years old and 55.6% were male. The RV/LV ratio showed significant improvement post intervention, with 21.2% decrease in the EKOS group (EG) and 35.6% in the Penumbra group (PG). The PG had a greater decrease in RV/LV (median change 0.396 (IQR, 0.347) vs. 0.207 (IQR, 0.306), p&lt;0.001). In the cohort, 25 adverse events were reported (13.2%). The rate of complications did not differ between the 2 groups, with 15.1% in EG and 10% in PG. In terms of bleeding complications, GUSTO moderate bleeding was observed in 8 cases (5 in EG and 3 in PG), while severe bleeding was observed in 3 (2 in EG and 1 in PG), including 1 intracranial hemorrhage in the PG. ICU admissions were higher in the PG (p&lt;0.001), but median hospital and ICU stays were comparable. No significant difference was found in the rate of in-hospital mortality (2.5% in EG, 4.3% in PG, p=0.672). Conclusion: Both CBT options are promising for treating submassive PE, with efficacy outcomes favoring Penumbra thrombectomy. Longer follow-up and randomized controlled trials are needed for definitive conclusions.
Abstract 12418: Effect of Atrial Fibrillation Cardioversion on the Severity of Mitral Insufficiency
Authors: Isaac Al Sallamin, Sameer M Mtour, Monther Nassar, Richard Pham
Journal: Circulation (2023)

To evaluate the effect of cardioversion with restoration of sinus rhythm in patients with atrial fibrillation (AF) and significant mitral regurgitation (MR) may improve the severity of MR. Atrial fibrillation (AF) is chronic, progressive and, may cause "permanent remodeling of the heart muscle, without structural abnormalities of the valve, reverse remodeling of the left atrium (LA) may be successful in AF. This retrospective cohort study included patients with atrial fibrillation who were hospitalized for cardioversion, received echocardiography during AF in mitral insufficiency, demonstrated significant mitral regurgitation, and underwent additional echocardiography within six months. Indices of the two echocardiograms were compared and used to investigate the effect of cardioversion on the severity of MR. A total of 417 patients were enrolled with a mean age of 74.6 ± 12, with 192 men (46%). On a 6 month follow-up echo, 254 patients (61%) returned to sinus rhythm. An improvement of two or more degrees of severity of MR was observed in 100 patients (24%). Of that number, 72 patients (72%) returned to sinus rhythm, compared with 28 patients (28%) who remained in AF (p = 0.009). Multivariate analysis found that the restoration of sinus rhythm was independently associated with an improvement of two or more degrees of severity, MR p = 0.01, OR = 1.9, CI 95% [1.2-3.0]. There was improvement in the end systolic left ventricular diameter from 3.79 ± 0.99 to 3.58 ± 0.91, p &lt; 0.01, a decrease in the diameter of the left atrium from 4.97 ± 0.64 to 4.79 ± 0.76, p &lt; 0.02, a decrease in the jet area from 11.37 ± 3.7 to 5.9 ± 1.7, p &lt; 0.01, a decrease in vena contracta from 0.66 ± 0.08 to 0.56 ± 0.07, p &lt; 0.01, and a decrease in the TIG from 41.85 ± 12.9 to 36.5 ± 10.7, p &lt; 0.01. There was also an improvement in the FS indices from 28.70 ± 10.17 to 32.17 ± 9.28, p &lt; 0.01.In the group with a slight improvement or no improvement in MR, there was an increase in end diastolic diameter from 5.10 ± 0.77 to 5.19 ± 0.79, p &lt; 0.02, and an increase in the diameter of the left atrium. There was no difference in the other indices. Cardioversion of atrial fibrillation to sinus rhythm in patients with significant mitral regurgitation was positively related to improvement in the severity of mitral insufficiency.
Abstract 14024: Proteomic Predictors of Transitioning From Metabolically Healthy to Unhealthy Status in Middle-Aged Adults: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Bige Ozkan, Justin B Echouffo, Kari E North, Vijay Nambi, Ron C Hoogeveen, Christie M Ballantyne, Elizabeth Selvin, Josef Coresh, Chiadi E Ndumele
Journal: Circulation (2023)

Background: Metabolic health status predicts adverse cardiovascular outcomes. Among persons with similar weight, some metabolically healthy individuals stay metabolically healthy, whereas others develop metabolic syndrome (MetS) over time. Hypothesis: Plasma proteins can identify biological correlates of transitioning from metabolically healthy to unhealthy status. Methods: We quantified 4,955 plasma proteins using SomaLogic v4.0 in stored samples of ARIC Visit 2 participants. We assessed metabolic health at Visits 2 (1990-92) and 4 (1996-98). We split the sample into 2/3 discovery and 1/3 validation subsamples and used Bonferroni-corrected p-values. Among metabolically healthy individuals (no MetS) at Visit 2, we evaluated the associations of baseline plasma protein concentrations with the odds of developing metabolic unhealthy status by Visit 4 using logistic regression. We performed gene product enrichment analysis to assess biological pathways associated with transitioning to metabolically unhealthy status. Results: We included 4,539 participants (mean age: 56±6 years, 58% women, 17% Black adults, mean BMI 25 kg/m 2 ). Adjusting for confounders, 306 proteins were significantly associated with transitioning from metabolically healthy to unhealthy status. After further adjustment for BMI, 121 proteins had significant associations (p&lt;10 -5 ). Of these, 49 proteins were validated (p&lt;0.05/121). We identified proteins with known associations (growth hormone receptor, adiponectin, plasminogen activator inhibitor) with metabolically unhealthy status and ~20 novel proteins (MXRA8, VOPP1, CRYZL1). Biological pathways overrepresented by these proteins included tyrosine kinase signaling, complement and coagulation cascades, and calcium signaling pathways. Conclusions: Plasma proteins are linked to developing metabolic unhealthy status over 6 years. These proteins could be useful in identifying and preventing poor metabolic health.
Abstract 14022: N-terminal Prohormone of B-type Natriuretic Peptide Levels Partly Mediate the Relationship of Advanced Hepatic Fibrosis With Mortality in Coronary Artery Disease
Authors: vardhmaan jain, Anurag Mehta, Terence Lee, Chang Liu, Nicholas W Chew, Yi-An Ko, Mohammad Siddiqui, Matthew Gold, Daniel A Gold, Nishant Vatsa, Shivang Desai, Shalimar ., Marat Fudim, Ambarish Pandey, Pankaj Arora, Elisabetta Bugianesi, Laurence Sperling, Arun Sanyal, Arshed A Quyyumi
Journal: Circulation (2023)

Background Advanced hepatic fibrosis (AHF) is associated with cardiac remodeling and adverse outcomes in patients with coronary artery disease (CAD). The mechanistic basis of this relationship and the contribution of the natriuretic peptide system is unclear. Hypothesis: The association of AHF with mortality in CAD is mediated by circulating N-terminal prohormone of B-type natriuretic peptide (NTproBNP) level. Methods: Patients undergoing cardiac catheterization for evaluation of CAD were enrolled in the Emory Cardiovascular Biobank and those with acute myocardial infarction, cirrhosis, and hepatocellular carcinoma were excluded. Plasma NTproBNP was measured, and Fibrosis-4 (FIB-4) index was calculated using age, alanine aminotransferase, aspartate aminotransferase, and platelet count. FIB-4 ≥2.67 was used to define AHF. Association of AHF and NTproBNP with all-cause mortality was studied using multivariable-adjusted Cox models and mediation analyses. Results: Study population included 3,432 patients with mean age 65 y and among them 32% were women, 24% were Black, and 15% had AHF. Median NTproBNP level was 2.5-fold higher among those with AHF (572, 95% CI 225-2203 pg/ml) compared with those without (223, 95% CI 93-689 pg/ml). AHF was independently associated with 49% higher all-cause mortality in multivariable-adjusted Cox models [HR(95% CI): 1.49 (1.26-1.77)]. NTproBNP stratified mortality risk associated with AHF ( Figure ). Patients with AHF and high NTproBNP (≥300 pg/ml) were at the highest risk, while risk in AHF and low NTproBNP (&lt;300 pg/ml) group was similar to those without AHF and low NTproBNP. NTproBNP was independently associated with mortality risk and mediated 61% of the effect of AHF on mortality in causal mediation analysis. Conclusion: NTproBNP partly mediates the excess mortality associated with AHF in patients with CAD. Therapeutic strategies targeting the natriuretic peptide system may help improve outcomes in this high-risk group.
Abstract 12995: South Asian Representation in Cardiovascular Disease Randomized Controlled Trials
Authors: Nishant Uppal, Aniruddh Patel, Deepak Bhatt, Pradeep Natarajan
Journal: Circulation (2023)

Introduction: South Asian individuals are at higher risk for atherosclerotic cardiovascular disease (ASCVD) compared to individuals of European descent. Although US practice guidelines uniquely recognize South Asian ancestry as a risk-enhancing factor for ASCVD, the degree to which South Asian individuals are included in clinical trials is unknown. We sought to evaluate South Asian representation in major cardiovascular disease (CVD) randomized controlled trials (RCTs) reported in major medical journals. Hypothesis: South Asian individuals are under-represented relative to the global South Asian population in CVD RCTs. Methods: We extracted citations of CVD RCTs reported from 2018 to 2022. Studies were identified as RCTs based on reported randomization of participants and the publication of post-randomization data. We determined self-reported representation rates for South Asian individuals across all studies and further stratified representation rates by clinical trial phase, type of intervention under investigation, and country of origin. Post-randomization participant representation rates were estimated for South Asian individuals and compared to other self-reported racial/ethnic groups. Results: 588,329 participants were enrolled across 128 included trials. Conditions studied included CVA (17.97%), HF (12.50%), CAD (11.72%), HTN (7.81%), ASCVD screening/prevention (7.81%), and others. 2,753 of all CVD RCT participants were South Asian individuals, corresponding to a representation rate of 0.47%. No South Asian individuals had available post-randomization data, whereas post-randomization data were reported for 164,035 white individuals, 20,459 Black individuals, and 6,040 Hispanic individuals. Conclusions: Although South Asian individuals comprise nearly a quarter of the global population and have well-documented excess CVD risk, they represent a small minority of CVD trial participants. No RCTs reported South Asian participant-level data, which limits the generalizability of study findings to South Asians.
Abstract 12789: Age-Related Disparities in Complications Among Women With Peripartum Cardiomyopathy
Authors: Sudhamai Akkaramani, Rahat A Memon, Kamleshun Ramphul, Raheel Ahmed, Shruti Aggarwal, Jasninder S Dhaliwal, Hasan Ahmad, Muzammil Farhan, Ali Hasan, Azeem Hassan, Shaheen Sombans, Hemamalini Sakthivel, Petras Lohana
Journal: Circulation (2023)

Introduction: While the exact pathogenesis of peripartum cardiomyopathy, a potentially life-threatening condition, is still unknown, its incidence is rising globally. We sought to understand the differences in outcomes and complications based on age. Hypothesis: Older women with peripartum cardiomyopathy would have adverse outcomes and complications. Methods: Our study sample consisted of females diagnosed with peripartum cardiomyopathy that required hospitalization care. Records from the 2016-2020 National Inpatient Sample were used for our study. They were divided into two age-based cohorts: 15-29 years and 30-40 years. We evaluated differences in complications between the two groups using multivariable regression. Results: Our analysis consisted of 20520 females diagnosed with peripartum cardiomyopathy, divided as 57.2% in the cohort of ages 30-40 and 42.7% between 15-29 years. Several differences in patient characteristics and comorbidities were noted, as reported in Table 1. Furthermore, patients of ages 30-40 demonstrated higher odds of reporting acute ischemic stroke (aOR 1.354, 95% CI 1.038-1.767, p=0.026) while having a reduced risk of cardiogenic shock (aOR 0.787, 95% CI 0.688-0.901, p&lt;0.01), as compared to those of ages 15-29. No statistically significant differences were noted for events of acute kidney injury (aOR 1.074, 95% CI 0.976-1.182, p=0.143), acute pulmonary edema (aOR 1.147, 95% CI 0.988-1.332, p=0.071), or mortality (aOR 0.978, 95% CI 0.742-1.290, p=0.877) (Table 2). Conclusions: Peripartum cardiomyopathy is a serious condition that requires appropriate care and management. Our study linked cases of ages 30-40 years with increased odds of acute ischemic stroke but lower odds of cardiogenic shock. Physicians should therefore be encouraged to monitor and screen as appropriate to improve outcomes closely.