tbuckley/cabot-search huggingface dataset:
Abstract 16823: The Mediating Effect of Perceived Stress on the Relationship Between Adverse Childhood Experiences and Depressive Symptoms in Rural Adults With Cardiovascular Disease
Authors: Jennifer Miller, Misook L Chung, Jennifer Smith, Debra K Moser
Journal: Circulation (2023)

Background: Adverse childhood experiences (ACEs), defined as abuse, household dysfunction, and neglect before age 18, increase the risk of depressive symptoms and cardiovascular disease (CVD). Fifty-two percent of people have reported 1 ACE with 6.2% reporting 4 or more. People in rural environments experience higher levels of stress and depressive symptoms, but little is known about the relationship of ACEs with stress and depressive symptoms in rural adults with CVD. Aim: To determine the prevalence of ACEs and the mediating effect of perceived stress on the relationship between ACEs and depressive symptoms in a sample of rural adults with CVD. Methods: We used Hayes PROCESS for SPSS (model 4) to determine the mediating effect of perceived stress (Cohen’s Perceived Stress Scale) in the relationship between ACEs (ACE questionnaire), and depressive symptoms (Patient Health Questionnaire-9) controlling for age, gender, financial status, and perceived control. Results: Of 210 rural adults with CVD (mean age 59 ± 13, ACE score 2.4 ± 2.5, and education 14 ± 3, 45.7% female, and 3.3% non-white) 20% reported 1 ACE with 30% reporting 4 or more. Adverse childhood experiences significantly predicted perceived stress (a = .2553, p = .001) and perceived stress significantly predicted depressive symptoms (b = .7419, p &lt; .001). The total (c = .4881, p = .001) and direct effects (c’ = .2987, p = .038) of ACEs on depressive symptoms in this sample were significant, as was the indirect effect of perceived stress (ab = .4144, 95% CI [.2449 - .6231]). Conclusion: The prevalence of ACEs in this sample of rural adults with CVD was 5 times higher than reported in the general population. Perceived stress is a mediator of the relationship between ACEs and depressive symptoms in rural adults with CVD. Interventions to decrease depressive symptoms in rural adults with CVD should include an assessment of ACEs and address management of perceived stress.
Abstract 15113: Diastolic Blood Pressure Predicts Mortality Risk in Patients With Cardiogenic Shock
Authors: Sanjana Adig, maya guglin
Journal: Circulation (2023)

Background: Cardiogenic shock is a heterogeneous group with poorly defined hemodynamic goals and predictors of mortality. A common target for management has been empirically set at systolic blood pressure of 90 mm Hg or above and a mean arterial pressure value of over 60 mmHg. In this study, we have compared systolic and diastolic blood pressure in survivors and non-survivors with cardiogenic shock, and then in the subsets in heart failure-induced (HF-CS) versus acute myocardial infarction-induced cardiogenic shock (AMI-CS). Methods: A cohort of consecutive patients with cardiogenic shock admitted to our institution from 10/30/2019 to 11/11/2022 was analyzed retrospectively. Blood pressure was recorded on admission and then at 24-, 48-, and 72 hours post-admission. Independent t-testing was performed to evaluate the significance. Results: A total cohort consisted of 226 patients with cardiogenic shock (mean age 60.2+-14.5 years, 66% male), including 120 (53.1%) HF-CS and 78 (34.51%) AMI-CS. Diastolic blood pressure was higher in survivors than in non-survivors. Among patients with CS who survived, the diastolic BP was statistically higher than the patients who died at 24 and 48 hours from admission (p= 0.007 and 0.01. respectively). In patients with HF-CS, diastolic blood pressure was also higher at the same time points (p= 0.033 and 0.035, respectively). Neither systolic nor diastolic blood pressure differed between survivors and non-survivors in AMI-CS. Systolic blood pressure was similar in survivors and non-survivors in the whole cohort and in both subsets. Conclusions: Our data suggest that diastolic BP could be an early, consistent, and more reliable predictor of mortality than Systolic BP for CS patients, especially in the subset of HF-CS.
Abstract 15043: Dapagliflozin Reduces Systemic NLRP-3, IL-1 and PCSK9 Levels in Preclinical Models of Short-Term Doxorubicin Cardiotoxicity: New Evidences of SGLT2i Use in Cardioncology
Authors: Nicola Maurea, Maria Laura Canale, Irma Bisceglia, Giuseppe Palma, Antonio Luciano, Francesca Bruzzese, Martina Iovine, Alessia Merola, Andrea Paccone, Domenico Gabrielli, Fabrizio Maurea, Vincenzo Quagliariello
Journal: Circulation (2023)

Background: Anthracyclines are an effective and widely used chemotherapy agent in the treatment of multiple solid organ tumors and hematologic malignancies. The use of anthracyclines as a standard cancer therapy is limited by the potential for the development of cardiac dysfunction, arrhythmias, and clinical heart failure. In recent five years, it was demonstrated that proprotein convertase subtilisin/kexin type 9 (PCSK9), a lipid metabolism-related protein, is a key orchestrator of immune infiltration in myocardial and cancer tissues and could regulate cardiac fibrosis and inflammation. PCSK9 is a protein with key roles in hepatic low density lipoprotein (LDL) homeostasis. PCSK9 systemic levels are associated to HOMA score and high insulin levels. Dapagliflozin exerts systemic ant-inflammatory properties and cardioprotective effects in diabetic and non-diabetic patients. Purpose: We hypothesized that Dapagliflozin, administered during doxorubicin, could reduce PCSK9 systemic levels in preclinical models. Methods: Female C57Bl/6 mice were untreated (Sham, n=6) or treated for 10 days with doxorubicin i.p at 2.17 mg/kg (DOXO, n=6), DAPA at 12 mg/kg (DAPA, n=6) or doxorubicin combined to DAPA (DOXO-DAPA, n=6). After treatments, plasma levels of PCSK9, IL-1β and CRP were analyzed through selective anti-mouse ELISA methods. Myocardial and liver expression of NLRP3-inflammasome and IL-1β were analyzed through ELISA method in tissue lysates after treatments. Results: DAPA associated to DOXO reduces significantly systemic levels of PCSK9 ( -37,5% vs DOXO group, p&lt;0,001). IL-1β and CRP levels were also reduced ( -47,3 and - 28,5 %, respectively; p&lt;0.05 for both). Myocardial and liver IL-1β and NLRP3 inflammasome expression were also reduced in DAPA/DOXO group vs DOXO and control, indicated beneficial metabolic and anti-inflammatory effects of SGLT2i. Conclusion: DAPA has been shown to reduce systemic levels of PCSK9 in preclinical models of short-term DOXO cardiotoxicity. To the best of our knowledge, this is the first evidence of SGLT-2/PCSK9 crass-talk in cardioncology therefore the overall picture of the study open a new window on the beneficial properties of DAPA against anthracyclines side effects.
Abstract 19069: Empagliflozin Improves Right Ventricular Remodeling and Right Ventricular Systolic Function in Non-Diabetic Hfref: Insights From Porcine and Human Studies
Authors: Carlos G Santosgallego, Juan Antonio Requena-Ibanez, Ariana Patricia Vargas Delgado, Kiyotake Ishikawa, Javier Sanz, Anuradha Lala, Johanna P Contreras, Donna M Mancini, Sean Pinney, Deepak Bhatt, Valentin Fuster, Juan J Badimon
Journal: Circulation (2023)

Background On top of improving heart failure outcomes, we and others have demonstrated that SGLT2 inhibitors induce reverse cardiac remodeling in HFrEF. However, these studies have focused on the left ventricle, while no information is available on the potential benefits of SGLT2i on the right ventricle (RV). Therefore, our objective is to investigate the effect of empagliflozin on RV remodeling and RV systolic function in non-diabetic HFrEF Methods Animal study: HFrEF was induced by means of proximal LAD occlusions for 2 hours in non-diabetic pigs. Pigs were then randomized to empagliflozin 10mg daily or placebo for 2 months (8/group). Pigs were evaluated with cardiac MRI. We previously reported that empagliflozin reduces LV volumes and improve LVEF (Santos-Gallego, JACC 2019) Human study : The EMPATROPISM clinical trial ((NCT03485222) randomized non-diabetic HFrEF patients to empagliflozin 10mg daily or placebo. All patients were evaluated with MRI. We previously reported that empagliflozin reduces LV volumes, while also improving peakVO2, LVEF, and quality of life (Santos-Gallego, JACC 2021) Results Animal study: Both groups were similar at baseline (RVESV 16.1±3.2 vs 15.8±2.1mL; RVEF 51.9±5.6 vs 52.7±4.7%; p=NS). Cardiac MRI showed that empagliflozin-treated pigs exhibited smaller RVEDV and RVESV at 2 months compared with control. Also treated animals exhibited better RVEF and better right ventriculoarterial coupling (Ees/Ea) vs control (Table) Human study: Both groups were similar at baseline (RVESV 87.4±35.6 vs 76.4±32.4 mL; RVEF 47.1±7.9 vs 49.2±9.1%; p=NS). Cardiac MRI showed that empagliflozin-treated patients experienced a reduction in RVESV vs placebo. Furthermore, empagliflozin-treated patients exhibited improvement in RVEF and in right ventriculoarterial coupling (Ees/Ea) vs control (Table) Conclusions Empagliflozin improves right ventricular remodeling and right ventricular systolic function in non-diabetic HFrEF
Abstract 12810: Short-Term Hospital Outcomes of Elderly Patients With Mechanical vs. Bioprosthetic Heart Valves Admitted for NSTEMI
Authors: Rahat A Memon, Kamleshun Ramphul, Abhimanyu Ravalani, Jasninder Dhaliwal, Nomesh Kumar, Yogeshwaree Ramphul, Shaheen Sombans, Fnu Bawna, Petras Lohana, Hemamalini Sakthivel
Journal: Circulation (2023)

Introduction: Valvular heart disease(VHD) is a significant cause of morbidity and mortality among the elderly. While the use, merits, and demerits of mechanical heart valves (MHV) and bioprosthetic heart valves(BHV) to treat VHD are well-documented in the literature, there needs to be more data on the outcomes following events of NSTEMI. Methods: We explored the 2016-2020 National Inpatient Sample for patients ages≥60 years hospitalized for a primary diagnosis of NSTEMI via their ICD-10 codes. We further retained those with a presence of MHV or BHV, and differences in outcomes between the two groups were evaluated. Results: Our study found 32775 adults of age 60 and more hospitalized with NSTEMI, which included 23670 (72.2%) cases with MHV, while 9105 (27.8%) patients had a BHV. No differences in mean Charlson Comorbidity Index (CCI) scores were found between the two groups (mean CCI in MHV patients: 4.14 vs. 4.22 in those with BHV, p=0.233). Compared to cases with BHV, those with MHV showed higher odds of acute kidney injury (aOR 1.108, p&lt;0.01), atrial fibrillation (aOR 1.110, p&lt;0.01), supraventricular tachycardia (aOR 1.46, p&lt;0.01), and use of CABG (aOR 1.289, p=0.031). However, patients with MHV were less likely to undergo PCI for NSTEMI than those with BHV (aOR 0.781, p&lt;0.01). No differences between the two cohorts were found for events of ventricular tachycardia (aOR 0.907, p=0.072), ventricular fibrillation (aOR 1.021, p=0.80), cardiogenic shock (aOR 1.012, p=0.876), or death (aOR 0.928, p=0.187). Finally, those with MHV reported a slightly more extended stay (mean length of stay 4.41 days) than those with BHV (mean length of stay 4.02 days, p&lt;0.01). Conclusions: Patients with MHV showed higher odds of complications such as AKI, Atrial fibrillation, supraventricular tachycardia, and use of CABG following NSTEMI while reporting lower odds of PCI use than those with BHV.
Abstract 16403: Toxoplasma Cardiomyopathy in a 36 Year HIV Positive Female
Authors: Ayushi Mohan, Srivaibhav Reddy, Noreen Mirza, Addi suleiman
Journal: Circulation (2023)

Introduction: Cardiac involvement of toxoplasmosis is extremely rare and can present as myocarditis, pericardial effusion, constrictive pericarditis, arrhythmias or heart failure. While acquired primary infection is severe in immunocompetent, it can be life-threatening among immunodeficient patients. Case: 36 Yr female with PMHx of HIV non-compliant with HAART, Toxoplasma infection in 2019 presented with weakness, dry cough &amp; substernal chest pain x 1-week, sharp type, increasing with lying flat. On presentation vitals were unremarkable. ECG showed diffuse T wave inversions. Troponins elevated at 5000s. MRI brain revealed multiple scattered bilateral cortical and cerebellar enhancing lesion suggestive of toxoplasmosis. Serology was positive for toxoplasmosis. Viral respiratory panel &amp; Sepsis work-up was negative. TTE on admission showed mild pericardial effusion and EF of 50-55%. Follow up TTE (day 7) revealed an EF of 25-30% with mild pericardial effusion pointing towards a toxoplasma induced myopericarditis leading to cardiomyopathy. TEE ruled out possibility of Endocarditis. Discussion: Patient was initiated on anti-toxoplasma therapy with pyrimethamine and sulfadiazine after toxoplasma cardiomyopathy was considered. After initial cardiopulmonary decompensation patient was intubated and needed pressor support. Over the course of next 2 weeks her condition improved with anti-toxoplasma therapy and was extubated. Conclusion: Toxoplasma myopericarditis is rare and a serious presentation among both immunocompetent and immunodeficient patients. Early intervention and diagnosis of Toxoplasma myopericarditis could prevent the progression of cardiomyopathy and improve overall prognosis.
Abstract 17672: Implications of Pcsk9 on Abdominal Aortic Aneurysm
Authors: Yae Hyun Rhee, Alicia Deng, Joshua M Spin, Colwyn Headley, Philip S Tsao
Journal: Circulation (2023)

Objective: Recent genome-wide association studies revealed a potential role of proprotein convertase subtilisin/kexin type9(Pcsk9) in the human abdominal aortic aneurysm(AAA) disease.Altered Pcsk9 gene expression and smaller AAA diameter were observed in murine AAA using the porcine pancreatic elastase(PPE) model in our lab. Pcsk9 increases plasma LDL-cholesterol,enhances tissue inflammation and induces vascular smooth muscle cell (VSMC) senescence, hallmarks in AAA.However, the exact cellular mechanisms of Pcsk9 in AAA disease remain unclear.Despite the absence of a pharmacological treatment for AAA, monoclonal Pcsk9 antibody therapies have proven effective against statin-resistant hypercholesterolemia.This study aimed to explore the impacts of Pcsk9 on aortic vascular inflammation and VSMC dedifferentiation with a view to better understanding AAA pathophysiology and providing a basis for future investigations into Pcsk9 inhibitors. Hypothesis: We hypothesized that local vascular injury escalates Pcsk9 expression,amplifying vascular inflammation and driving VSMC towards dedifferentiation that further advances AAA. Conversely,Pcsk9 inhibition will mitigate these processes. Methods: AAA was induced by PPE model in wildtype C57Bl/6 mice and Pcsk9 knock-out (KO)mice.Sonography was used to evaluate the aneurysm growth. Single-cell RNA sequencing was employed to examine local changes in the aortic wall. Local vascular Pcsk9,pro-inflammatory and VSMC marker gene/protein expression were quantified using qPCR and immunohistochemistry.VSMCs were treated with exogenous Pcsk9 in vitro to assess metabolism via Seahorse. Results: Reduced AAA diameters were observed in Pcsk9 KO mice compared to wildtype controls. Significant upregulation of local Pcsk9 expression accompanied AAA induction. Single-cell RNA sequencing revealed altered gene expression profiles across vascular cell populations. In vitro,VSMCs displayed changes in marker gene/protein expression after treatment with exogenous Pcsk9, alongside metabolic changes (Mann-Whitney Test). Conclusions: The findings suggest a significant role of Pcsk9 in AAA pathogenesis. Its inhibition appears to mitigate AAA growth,indicating a promising treatment target for AAA.
Abstract 13532: Long-Term Survival of Different Heart Failure Categories in Patients Discharged Owing to Coronary Artery Disease With/Without Acute Coronary Syndrome
Authors: Chao-Lun Lai, Tsung-Yu Ko, Jesse Chih-Wei Lin, Ting-Chuan Wang, Min-Tsun Liao, Heng-Yu Pan, Sheng-Fu Liu, Hsien-Li Kao, K. Arnold Chan, Yi-Lwun Ho
Journal: Circulation (2023)

Background: Heart failure (HF) has been classified into distinct phenotypes based on left ventricular ejection fraction (LVEF). We conducted this retrospective cohort study to explore the long-term survival prognosis of different types of HF especially the HF with improved ejection fraction (HFimpEF) group. Methods: We collected patients who had ever been hospitalized owing to coronary artery disease or acute coronary syndrome between July 2006 and June 2017 at National Taiwan University Hospital (NTUH) and NTUH Hsin-Chu Branch. Patients were classified as (1) HF with reduced ejection fraction (HFrEF); (2) HFimpEF; (3) HF with mildly reduced ejection fraction (HFmrEF); (4) HF with preserved ejection fraction (HFpEF); according to echocardiography-derived LVEF during or after the index hospitalization. The date of the first echocardiography during or after the index hospitalization was defined as the index date. All patients were followed from their index date until death or the end of the study (December 31 2017), whichever occurred first. Results: Totally, 11549 patients were categorized into 4 groups (HFrEF group, n = 986; HFimpEF group, n = 461; HFmrEF group, n = 1454; and HFpEF group, n = 8648). The crude mortality rate during follow-up in HFrEF group, HFimpEF group, HFmrEF group, and HFpEF group was 60.4%, 28.0%, 36.6%, and 18.3%, respectively. Patients in HFimpEF group, HFmrEF group, and HFpEF group all possessed a significantly reduced risk of all-cause mortality compared with HFrEF group (adjusted hazard ratio [HR] 0.241, 95% confidence interval [CI] 0.199-0.292 for HFimpEF group; 0.443, 95% CI 0.393-0.500 for HFmrEF group; and 0.292, 95% CI 0.262-0.324 for HFpEF group). Using the time-varying Cox regression model to deal with the immortal time bias, we found a persistent lower risk of all-cause mortality in patients in HFimpEF group compared with patients in HFrEF group (adjusted HR 0.579, 95% CI 0.467-0.718). Conclusion: Patients in HFrEF group had the worst long-term survival prognosis and patient in HFpEF group had the best long-term survival prognosis. Patients in HFimpEF group represented a distinctive population with good survival prognosis than HFrEF group and HFmrEF group.
Abstract 15725: Access to Pacemaker Implantation Amongst Medicare Beneficiaries: Travel Distance and Time to Nearest Clinician
Authors: Pegah Khaloo, Kevin Wheelock, Sohum Kapadia, Rohan Khera
Journal: Circulation (2023)

Background: Despite being an essential procedure with rising use in the United States, the availability and accessibility of procedural care for a permanent pacemaker are not known. We investigated access to pacemaker implantation among Medicare beneficiaries. Methods: US Medicare physician claims from 2020, and county population characteristic data from AHRQ were used to evaluate the density of providers and beneficiaries across states and counties. For each US zip code, we determined the closest pacemaker implantation center using the haversine formula, then assessed the travel duration for each route using the Google Maps API. Results: There was a median of 5 providers performing pacemaker placement per 100,000 individuals over 65 years across all states, with an IQR of 4.5 to 6. At the county level, only 20% of counties in the US had a center offering transvenous pacemaker implantation, and 4% had a center offering leadless pacemakers. Individuals in metropolitan counties drove a median 29 (IQR 18 - 47) minutes to reach a center for pacemaker implantation, while those in non-metropolitan counties drove a median of 72 (IQR 52 - 102) minutes. In counties where &gt;25% of the population is ≥65 years old, the median drive time to a pacemaker center is 86 (IQR 57 - 126) minutes. Residents of counties with a lower median household income (Spearman’s r = 0.45, p &lt; 0.001) and a higher percentage of residents using public insurance had longer drive time to a pacemaker center (r = 0.23, p &lt; 0.001). Out of the estimated 55,356,000 individuals ≥65 years old in the United States, 20,000,000 (36%) had to drive more than one hour, and 4,383,955 (8%) had to drive more than two hours to a site where a pacemaker implantation procedure is performed. Conclusion: Over one-third of the population in the United States has significant access issues to basic electrophysiologic care, highlighting the need for increased resources and improved accessibility.
Abstract 13242: Annual Body Weight Change and Subsequent Prognosis in Heart Failure With Preserved Ejection Fraction: Insights From the PURSUIT-HFpEF Registry
Authors: Masato Okada, Nobuaki Tanaka, Katsuomi Iwakura, Masahiro Seo, Takaharu Hayashi, Masamichi Yano, Akito Nakagawa, Yusuke Nakagawa, Shunsuke Tamaki, Takahisa Yamada, Yasumura Yoshio, Yohei Sotomi, Daisaku Nakatani, Shungo Hikoso, Yasushi Sakata
Journal: Circulation (2023)

Introduction: Maintaining optimal body weight is important in heart failure management. Weight gain (WG) may signal excessive caloric intake and fluid retention, whereas weight loss (WL) would imply cachexia. Both conditions could affect the prognosis of heart failure with reduced ejection fraction. However, the significance of WG and WL in patients with heart failure and preserved ejection fraction (HFpEF) has not been well established. Methods: An analysis was performed from a prospective multicenter observational registry for HFpEF (PURSUIT-HFpEF Registry) conducted in the Osaka region of Japan. Of 1231 patients who enrolled in the registry, we enrolled 662 patients (age, 82±9 years; females, 54.1%; body mass index, 22.3±4.3kg/m 2 ; atrial fibrillation, 38.3%) whose weight at discharge and one year later were both available. WG and WL were defined as a gain or loss of ≥5% weight between baseline and 1 year, respectively. Other patients who did not demonstrate a significant change in weight were categorized as having a stable weight (SW). All-cause mortality was the primary endpoint. Results: During 1-year, the median body weight slightly increased from 52.1 (interquartile range [IQR]: 45.1-61.9) to 53.0 kg (IQR 45.0-63.0) kg (p &lt;0.001), with a median change of 0.6 kg (IQR: -1.8-2.8). A total of 182 (27%), 125 (19%), and 355 (54%) patients experienced WG, WL, and SW, respectively. During a follow-up of 603 days (IQR: 329-982), 149 patients died. The mortality rate was highest in patients experiencing WL, followed by those experiencing WG and SW (30.2% vs. 21.5% vs. 18.0%, respectively; log-rank p = 0.006). After adjusting for potential confounders, Cox regression analysis revealed that WL, not WG, was independently associated with higher mortality (hazard ratio 2.44 [95% CI 1.51-3.95], p &lt;0.001). Conclusions: Significant number of patients with HFpEF experienced WG and WL within a year. Patients who experienced WL had a higher risk of mortality compared to those who experienced WG and SW. These results highlight the importance of monitoring body weight changes in the management of HFpEF.