tbuckley/cabot-search huggingface dataset:
Abstract 15705: Perceived Control Over Own Health Buffers the Negative Impact of Patient Symptom Burden on Quality of Life in Patient-Caregiver Dyads: A Dyadic Mediation Analysis
Authors: Misook L Chung, Chin-Yen Lin, Jennifer L Miller, Debra K Moser
Journal: Circulation (2023)

Introduction: Patients with heart failure (HF) experience multiple physical and psychological symptoms that are associated with poor quality of life (QoL) for patients and family caregivers. Perceived control is known to buffer the adverse consequences of symptom burden on QoL among patients and caregivers at the individual level. However, there is limited knowledge about these associations within dyad members. Our aim was to determine whether perceived control over one’s personal health mediated the association of patient symptom burden and QoL in each member of the dyad. Methods: In this cross-sectional study, patients with HF (N= 154, 65% male, 50% NYHA III/V) reported physical and psychological symptom burden (Memorial Symptom Assessment Scale-HF). Informal caregivers (N = 154, 76% female) and patients completed surveys of perceived control (Control Attitudes Scale-Revised) and physical and mental well-being (MOS Health Survey-36v2). Dyadic data were analyzed using four multilevel Actor Partner Independence Mediation Models. Results: Symptom burden was associated with perceived control of each dyad member (P &lt;.05). Physical symptom burden was directly associated with physical well-being for patients, not caregivers. Physical and psychological symptom burden was directly associated with mental well-being for each dyad member. Perceived control significantly mediated the association of physical symptom burden with physical and mental well-being in each dyad member (Figures A &amp; C). Similarly, perceived control mediated the association of psychological symptom burden with physical and mental well-being in each dyad member (Figures B &amp; D). Perceived control did not influence QoL in partners. Conclusions: Physical and psychological symptoms in HF patients were linked with each dyad member's QoL through perceived control over their health. Fostering perceived control may minimize the negative impact of symptom burden on the QoL of dyad members.
Abstract 16052: Non-Canonical Mechanisms of BARKct-Mediated GRK2 Inhibition in Heart Failure Rescue
Authors: Heidi Cho, Kurt Chuprun, Erhe Gao, Walter J Koch
Journal: Circulation (2023)

Introduction: Significant GRK2 upregulation during HF results in desensitization of βARs. βARKct is a peptide inhibitor of GRK2 comprised of the last carboxyl terminal region of GRK2, and prevents GRK2 binding and βAR desensitization. βARKct overexpression attenuates HF and improves outcomes in animal models. Following oxidative stress, MAPKs phosphorylate the Ser670 (S670) residue of GRK2, which induces GRK2 binding to Hsp90 and localization to mitochondria, initiating pro-death pathways. As S670 is also found in βARKct, it may prevent endogenous GRK2 accumulation in the mitochondria. Hypothesis: βARKct-mediated cardioprotection in HF is due primarily to mitochondrial GRK2 blockade by βARKct. Methods: We generated cardiac-specific mutant βARKct-S670A transgenic mice harboring a Ser-to-Ala mutation at the S670 residue to prevent Hsp90 binding and allow for endogenous GRK2 to continue to translocate to the mitochondria upon ischemic injury, while retaining βARKct in the cytosol to act on βAR signaling pathways. Additionally, we have generated AAV vectors to deliver WT βARKct, βARKct-S670A, and phosphomimetic βARKct-S670D peptides in mice. We performed in vivo hemodynamic analysis to assess cardiac function in βARKct and βARKct-S670A transgenic mice. Additionally, intracellular cAMP levels in AC16 cardiomyocytes transfected with βARKct or βARKct-S670A, and βARKct-S670D plasmids were quantified in response to increasing doses of isoproterenol. Results: Hemodynamic analysis of the βARKct-S670A mice has demonstrated increased baseline contractility in βARKct-S670A mice compared to NLC mice, indicating comparable cardioprotective effects to βARKct mice lacking the point mutation, which are mediated by canonical pathways. In vitro cAMP quantification revealed AC16s transfected with βARKct, βARKct-S670A, and βARKct-S670D plasmids increased cAMP accumulation in response to increasing doses of isoproterenol compared to control. Conclusions: Studies characterizing the mitochondrial pathways involved in HF rescue following ischemic injury are ongoing. These findings will identify new mechanistic information of GRK2 inhibition for HF, and elucidate a new method for attenuating mitochondrial dysfunction during HF.
Abstract 14266: Is the Association Between Coronary Artery Disease and Adverse Brain Health Causal? A Combined Observational and Mendelian Randomisation Study
Authors: Constantin-Cristian Topriceanu, Resham Hussain, Caroline Dale, Chloe M Park, Nishi Chaturvedi, Ghazaleh FATEMIFAR, Victoria Garfield
Journal: Circulation (2023)

Introduction: Although coronary artery disease (CAD) is associated with worse brain health in observational studies, whether this is causal remains elusive. Aim: To examine observational associations between CAD and brain health, and use Mendelian randomisation (MR) to test for causal relationships. Methods: 472,120 UK Biobank participants were included. Outcomes were divided into brain morphology (white matter hyperintensity volumes [WMHVs] and hippocampal volumes [HVs]) and cognitive outcomes (reaction times [RTs] and visual memory [VM]). Generalized linear models were employed to explore the association between CAD and these brain health outcomes after adjusting for demographics, cardiometabolic risk factors and medications. To determine whether the observed associations were causal, we fitted MR inverse-variance weighted models, alongside sensitivity analyses for horizontal pleiotropy. Results: Observational analyses showed that CAD participants had 1.8% (95% confidence interval [CI] =[1.5, 2.0]) longer (worse) RTs but this was attenuated to 1% after adjusting for antihypertensives, diabetes or lipid-lowering drugs; 15.9% [7.0, 25.8] greater WMHVs but this was attenuated to the null after controlling for cardiometabolic risk factors; and 1.7% [1.0, 2.5] lower HVs (1% after adjusting for antihypertensives). There was no association between CAD and VM. MR analyses showed that individuals with greater CAD genetic liability made 1.01% [1.00, 1.01] more errors on VM tests but there was no evidence of causal associations with RTs, WMHVs and HVs. Conclusion: Observational analyses showed that CAD was associated with worse brain health, and addressing cardiometabolic risk factors was beneficial. However, MR analyses suggested a causal association only between genetic liability to CAD and worse VM. Future research should explore non-cardiometabolic factors (e.g., glutamate toxicity) to reduce cognitive impairment risk in individuals with CAD.
Abstract 14785: HEART Score Utilization - Revisited
Authors: Punit Arora, Kamil Cwikla, Christine Dankha, David Sutherland, Anthi Katsouli
Journal: Circulation (2023)

Introduction/Background: Chest pain accounts for approximately 7.6 million visits a year to the Emergency Department (ED) in the US. With use of the HEART score, a validated instrument helps to risk stratify patients with chest pain into low, medium, and high-risk groups. Low risk patients have a 1.6% chance of experiencing a major adverse cardiac event (MACE) within 30 days and are safe discharges from the ED without further testing. Hypothesis: We hypothesize that a targeted intervention to educate providers to use the HEART score will lead to decreased testing of low-risk patients without increase in MACE. Methods: Targeted interventions: (1) we provided teaching sessions on how to use the HEART score and (2) HEART score template was embedded into admitting notes on the unit EMR. Via retrospective chart review, investigators calculated a HEART score for patients who presented with chest pain and were admitted to LUMC. We calculated the rate of further cardiac testing and length of stay (LOS) for each risk stratified group, before and after our intervention. Chi-square tests are used to evaluate for association. Results/Data: Pre-intervention (n=259), only 30.5% patients had a documented HEART score. 46.7% were low risk, of which 30.5% underwent inpatient stress test or further cardiac testing. Low-risk patients that underwent further workup had increased LOS (p=0.0048). Post intervention (n=79), 58.1% patients had a documented HEART score, a statistically significant increase (p&lt;0.001). Of those considered low risk, fewer had further cardiac testing ordered (p&lt;0.001). No patient with a low-risk HEART score experienced a MACE within 30 days. Conclusions: Provider education is an effective method to increase HEART score utilization and reduce inpatient cardiac testing of low-risk patients with chest pain. Our study demonstrated an increase in documentation of the HEART score and a reduction of further testing of low-risk patient groups without worse outcomes.
Abstract 18131: Outcomes of Catheter-Based Thrombectomy versus Surgical Embolectomy Among Patients With Massive Pulmonary Embolism: A Nationwide Analysis From the United States
Authors: Mahmoud Ismayl, Hasaan Ahmed, Joshua May, Anas Hashem, Omar Hamadi, Andrew M Goldsweig
Journal: Circulation (2023)

Background: Clinical outcomes of catheter-based thrombectomy (CBT) compared with surgical embolectomy (SE) in patients with massive pulmonary embolism (mPE) have not been previously examined. Methods: We conducted a retrospective cohort study using the 2016-2020 National Inpatient Sample database to compare the outcomes of CBT versus SE in patients with mPE. Outcomes of interest included risk-adjusted in-hospital mortality, major bleeding, stroke, acute kidney injury (AKI), hospital length of stay (LOS), and total cost. Results: The total cohort included 5,845 patients with mPE, of which 5,490 (93.9%) underwent CBT and 215 (3.7%) underwent SE. After risk-adjustment, CBT had similar odds of in-hospital mortality (adjusted odds ratio [aOR] 1.49, 95% confidence interval [CI] 0.60-3.66, p=0.37) and stroke (aOR 1.49, 95% CI 0.30-7.38, p=0.62), lower odds of major bleeding (aOR 0.28, 95% CI 0.13-0.63, p&lt;0.01), and higher odds of AKI (aOR 2.40, 95% CI 1.11-5.17, p=0.02) compared with SE. CBT had a similar LOS (p=0.58) and total cost (p=0.23) compared with SE. Between 2016 and 2020, there was a temporal increase in the performance of CBT in patients with mPE (p trend &lt;0.01). Conclusions: In patients with massive PE, CBT was associated with similar in-hospital mortality, stroke, LOS, and total cost, lower major bleeding, and higher AKI compared with SE. Randomized controlled trials are indicated to confirm our findings.
Abstract 18503: Endogenously Released Factors From Doxorubicin-Treated Breast Cancer Spheroids Contribute to Toxicity in Human Cardiomyocytes: Protective Effect of Combination Therapy With PDE5-mTOR Inhibitors
Authors: Anindita Das, Nuhash Bhuiyan, Varun Kodali, Valerie Lau, Simi Chakravarty, Arun Samidurai, Rakesh C Kukreja
Journal: Circulation (2023)

Background: We previously demonstrated that a novel combination therapy with the phosphodiesterase 5 (PDE5) inhibitor (sildenafil, Sild) and mTOR inhibitor (rapamycin, Rapa) potentiates doxorubicin (DOX)-induced breast cancer cell killing, but attenuates cardiotoxicities. However, it remains unclear whether there are any factors released from cancer cells treated with DOX that contribute to the injury in cardiomyocytes, which can be modified by Sild and Rapa in combination. Therefore, we designed experiments using spheroid cultures of breast cancer and human AC-16 cardiomyocytes to determine the role of endogenously released factors following treatment with DOX. Methods &amp; Results: Spheroid cultures of breast cancer MDA-MB-231 cells were treated with DOX (1 μμ), and/or Sild (10 μμ) and Rapa (100 nμ) for 48 hours. The medium was replaced and spheroids were further incubated for 48 hours in the fresh medium. Thereafter, the AC-16 cardiomyocytes were treated with the medium from drugs-treated spheroids for 48 hours. Our results showed that treatment with DOX and/or Sild and Rapa was highly effective in reducing the size of spheroids as compared to the control ( Fig. A ). Moreover, Western blots showed that p-mTOR/mTOR and p-S6/S6 were induced and p-AKT/AKT was suppressed after DOX treatment in cancer cells, which were normalized following treatment with Sild and Rapa ( Fig. B ). The medium from DOX-treated spheroids caused increase of cardiomyocytes death as assessed by trypan blue exclusion assay, which was attenuated by co-treatment with the medium from Sild and Rapa treated spheroids ( Fig. C ). Conclusion: These results suggest that cardiotoxicity of chemotherapeutic agents could be partly contributed by the endogenously released unknown factors from tumors, which can be modulated by a novel combination treatment with Sild and Rapa via regulating mTOR-signaling pathways.
Abstract 15192: The Impact of Fontan Circulatory Failure on Heart Transplant Survival: A 20 Center Study
Authors: Kurt R Schumacher, David N Rosenthal, Adriana Batazzi, Sunkyung Yu, Garrett Reichle, Maria Bano, Shriprasad R Deshpande, Matthew O'Connor, Humera Ahmed, Sharon Chen, Lydia Wright, Steven J Kindel, Anna Joong, Michelle Ploutz, Brian D Feingold, Justin Godown, Chad Y Mao, Angela Lorts, Kathleen Simpson, Aecha Ybarra, Marc E Richmond, Shahnawaz Amdani, Jennifer Conway, Elizabeth Blume, Melissa Cousino
Journal: Circulation (2023)

Introduction: Fontan circulatory failure (FCF) is a chronic state in palliated single ventricle heart disease with high morbidity and mortality including heart failure, multisystem end-organ disease, and need for heart transplant (HT). Specific FCF morbidities have not been rigorously defined limiting study of how FCF morbidities impact pre- and post-HT outcomes. Hypothesis: FCF-specific morbidities affect survival from HT waitlisting (WL) through 1-year post-HT. Methods: This 20-center, retrospective cohort study collected demographic, medical/surgical history, WL data, and peri- and post-HT data in Fontan patients WL since 2008. Using Delphi methodology, investigators defined FCF-specific morbidities and collected data. Appropriate univariate 2-group statistics compared surviving individuals with those who 1) died anytime from WL to 1-year post-HT, 2) died on the WL, 3) died within 1-year post-HT. Multivariable logistic regression determined independent risk factors for mortality between WL and 1-year post-HT. Results: Of 409 WL patients, 24 (5.9%) died on the WL. Of the 316 (77%) who underwent HT, 27 (8.5%) did not survive to 1-year. Univariate risk factors for WL death included higher aortopulmonary collateral burden, &gt; 1 hospitalizations in prior year, younger age, sleep apnea, higher NYHA class, non-enrollment in school or work, and single-parent home. Risk factors for 1-year post-HT mortality included HLHS diagnosis, patent fenestration, anatomic Fontan obstruction, clinical cyanosis (pulse oximetry &lt; 90%), polycythemia, portal variceal disease, psychiatric disease requiring treatment, and higher HLA class II PRA. For the 15% of patients not surviving from WL to 1-year post-HT, independent risk factors for mortality included &gt;1 hospitalization in the year prior to WL (aOR 2.0, p=0.05) and clinical cyanosis (aOR 5.0, p=0.002). Notably, some FCF morbidities did not impact post-WL survival including protein-losing enteropathy, plastic bronchitis, and kidney disease. Conclusions: Fontan-palliated patients continue to have high mortality from WL through HT. Among FCF specific morbidities, cyanosis is associated with worsened survival and needs further study. Continued study of FCF phenotype is possible via this dataset.
Abstract 15228: Impact of Gender and Left Ventricular Ejection Fraction on Health-Related Quality of Life and Its Change in Patients With Heart Failure
Authors: Ji-Hun Jang, Dae-Young Kim, Sung-Hee Shin
Journal: Circulation (2023)

Introduction: Health-related quality of life (HRQoL) is an important part in managing patients with heart failure (HF). However, the influence of clinical factors on HRQoL in HF remains limited. Hypothesis: This study aimed to examine HRQoL changes based on gender and left ventricular ejection fraction (LVEF) among patients with HF. Methods: A total of 199 patients hospitalized for acute HF (mean age, 71±14 years; men:women=119:80; mean LVEF=42±16) were enrolled in a prospective way from Jan 2022 to Jan 2023. Baseline and 4-month follow-up Kansas City Cardiomyopathy Questionnaire (KCCQ) scores were assessed. Patients were categorized into 4 subgroups: Group 1, women with LVEF≥50% (n=37); Group 2, men with LVEF≥50% (n=26); Group 3, women with LVEF&lt;50% (n=43); Group 4, and men with LVEF&lt;50% (n=93). Results: Women demonstrated lower KCCQ clinical and overall summary scores than men at baseline (p=0.003, 0.004, respectively) and 4-month follow-up (p=0.029, 0.038, respectively) after adjusting for age and body mass index. In addition, these scores tended to be lower in patients with LVEF ≥50% than those with LVEF &lt;50% at both baseline and follow-up (all p&lt;0.05). When we assessed KCCQ scores according to group, group 1 showed the lowest KCCQ overall summary score (KCCQ-OS: 36.9 [IQR 22.9-49.8], p=0.004) and clinical summary score (KCCQ-CS: 37.8 [IQR: 24.5-51.1], p=0.001). Also, the scores for physical limitation, symptom frequency, symptom burden, social limitation, self-efficacy scale, and total symptom score were lowest in Group 1 (all p&lt;0.05). Although HRQoL improved across all groups, the follow-up KCCQ-OS and KCCQ-CS scores remained lowest in Group 1 (KCCQ-OS: 54.0 [IQR 44.3-64.4], p=0.026; KCCQ-CS: 56.5 [IQR: 45.0-63.9], p=0.031). Conclusions: Among patients with HF, women with LVEF≥50% reported significantly worst HRQoL even after HF treatment, suggesting more attention should be paid to HRQoL in managing this specific population during HF treatment.
Abstract 15684: Adherence and Persistence to SGLT2 Inhibitors in Patients With Heart Failure
Authors: Shogo Kono, Jungyeon Moon, Alice Chong, Jiming Fang, Dennis T Ko, Peter Austin, Clare Atzema, David Naimark, Jacob A Udell, Therese Stukel, Karen Tu, Gillian Booth, Cynthia Jackevicius
Journal: Circulation (2023)

Introduction: While originally used solely as antihyperglycemic agents, sodium-glucose cotransporter 2 inhibitors (SGLT2i) are now recommended for use in heart failure (HF) to reduce hospitalization and cardiovascular mortality. Unfortunately, benefits of treatment can only be fully realized if a patient is adherent to therapy. While SGLT2i adherence has been found to be suboptimal in diabetes populations, SGLT2i adherence has not been well-studied in patients with HF. Since medication non-adherence in HF tends to be high in general, and can lead to worse clinical outcomes, this study aimed to estimate SGLT2i adherence/persistence rates in a population-based cohort of HF patients. Methods: This retrospective cohort study included patients ≥65 years discharged alive from a hospital in Ontario, Canada between 4/2016 and 3/2021, who had a primary diagnosis of HF and were dispensed a SGLT2i prescription. Prescription claims were used to identify and calculate 6-month and 1-year SGLT2i adherence and 1-year persistence, from the first date of fill for an SGLT2i. Adherence was calculated as the proportion of days covered (PDC), with PDC≥80% defined as “good” adherence. Persistence was calculated with a “permissible” gap of 30 days allowed before being considered non-persistent. A cumulative incidence function was utilized to account for the competing risk of death in persistence calculations. Results: There were 5,257 eligible patients (59% male, mean age 76.94±7 years, 73.8% with diabetes), for whom empagliflozin (64.9%), dapagliflozin (25.5%) and canagliflozin (9.5%) were used. The overall mean PDC was 83.9% at 6-months and 80.5% at 1-year, with the proportion of patients with “good” adherence (PDC≥80%) at 76.2% and 72.5%, respectively. Persistence to all prescribed SGLT2i was 71.3% at 1-year, with highest persistence with dapagliflozin at 74.4% and lowest persistence with canagliflozin at 68.1% [p=0.01]. Conclusion: In this HF cohort on SGLT2i, nearly 3 out of 4 patients were highly adherent and persistent at one year. SGLT2i adherence/persistence rates are higher than seen in studies in diabetes populations. Further studies are needed to identify those at risk of non-adherence/non-persistence and to examine association with clinical outcomes.
Abstract 18280: Five-Year Major Amputation Risk in Patients Undergoing Lower Extremity Bypass Taking into Account All-Cause Mortality Risk and Age Groups
Authors: Gaelle Romain, Jacob Cleman, Carlos Mena-Hurtado, Kim G Smolderen
Journal: Circulation (2023)

Background: Selecting good lower extremity bypass (LEB) surgery candidates for chronic limb threatening ischemia (CLTI) is important to optimize risk-benefit ratios for amputation and death. As mortality risks may be different across age groups, we aimed to examine whether amputation risks across age groups differ by their differential competing risk of death. Methods: Individuals with CLTI undergoing infrapopliteal LEB from 2014 to 2019 in the Medicare linked Vascular Quality Initiative registry were included. The cumulative incidence Function (CIF) for 5-year mortality and major amputation in age groups &lt;65 and ≥65 years, was calculated by Aalen-Johansen, taking mortality into account, and compared against the CIF derived from a traditional Kaplan-Meier, not accounting for competing death. The major amputation risk by age groups was estimated using a Fine and Gray competing risk model (sHR) accounting for competing death and traditional Cox regression (HR) not accounting for competing death. Results: A total of 2,105 patients were included (22% aged &lt;65 years; 70% male, 7% Hispanic, and 18% black). Amputation rates in &lt; 65 vs. ≥65 years were 35.2% and 19.2%; for mortality 34.4% and 44.6%, respectively. In those &lt;65 years, death without amputation was over-estimated by a relative difference of 42%; and major amputation by 16%. Death without amputation in the ≥65 years group was over-estimated by 18%; amputation risk was over-estimated by 23%. When not accounting for competing death risk, adjusted amputation risk for &lt;65 vs ≥65 years was HR 1.17 95%CI 0.90 -1.50 vs. sHR = 1.26 95%CI 0.97-1.62 in the competing risk model. (Table) Conclusions: Younger individuals with CLTI have the highest amputation vs. mortality risk; for those older than 65 years it is the other way around. Collapsing estimates across age groups, while not incorporating competing death risk overestimates amputation risk and can mislead the interpretation of therapeutic benefits of CLTI interventions.