tbuckley/cabot-search huggingface dataset:
Abstract 4143067: Enhanced Mevalonate Pathway Through Laminar Flow-Induced DDIAS/ACLY Complex Supports Antioxidant Pathways and Angiogenesis Post-Hindlimb Ischemia
Authors: Khanh Chau, Sivareddy Kotla, Venkata Subrahman K Samanthapudi, Jonghae Lee, Abigail Osborn, Oanh Hoang, Gilbert Mejia, Junichi Abe, NHAT TU LE
Journal: Circulation (2024)

Background: Atherogenesis often develops in regions with disturbed blood flow (d-flow), involving increased ERK5 and p53 SUMOylation due to SENP2 T368 phosphorylation, leading to increased ERK5 and p53 SUMOylation, contributing to endothelial cell (EC) activation. Conversely, laminar flow (l-flow) induces SENP2 S344 phosphorylation, reducing ERK5 and p53 SUMOylation, thereby suppressing EC activation. The presence of senescent ECs in atherosclerotic plaques suggests that d-flow-induced EC senescence may contribute to atherogenesis, possibly due to metabolic changes. EC glycolysis is crucial for NO production and atheroprotection, however, it is inhibited by l-flow, indicating that l-flow protective effects extend beyond glycolysis. Methods: In ECs from wild-type mice exposed to l-flow, the expression of DDIAS increases, regulated by SENP2 S344 phosphorylation. DDIAS interacts with ACLY, a key regulator of fatty acid metabolism and vascular function. We performed LC-MS and IC-MS analyses on ECs with DDIAS knocked down or control siRNA exposed to l-flow, using 13 C 2 -gucose or 13 C 5 -glutamine to trace metabolic changes. HMG-CoA, acetyl-CoA, and CoQ levels were measured using LC-MS and triple quadrupole LC-MS/MS. Results: L-flow enhances glycolysis and glutaminolysis, significantly increasing TCA cycle intermediates through upregulated glutamine pathways. DDIAS expression and its interaction with ACLY are also increased by l-flow. Without DDIAS, the ACLY-mediated mevalonate pathway is inhibited, reducing l-flow-induced antioxidant mechanisms. Thus, the DDIAS-ACLY complex is crucial for the antioxidant response triggered by L-flow, which is essential for supporting angiogenesis after hindlimb ischemia. L-flow-induced increases in HMG-CoA and CoQ are inhibited by DDIAS depletion, highlighting the importance of DDIAS in maintaining the balance of metabolic and antioxidant pathways under L-flow. We are investigating the role of DDIAS-ACLY complex on l-flow-mediated upregulation of glycolysis and glutaminolysis. Conclusion: DDIAS plays a key role in mediating l-flow atheroprotective effect by directly interacting with and activating ACLY, essential for the mevalonate pathway and subsequent HMG-CoA and CoQ biosynthesis. Under l-flow conditions, ECs preferentially utilize glutamine over glucose for TCA cycle intermediates, underscoring the importance of the DDIAS-ACLY complex in supporting EC protection and function through enhanced metabolic pathways.
Abstract 4143120: Efficacy of Sacubitril-Valsartan Compared with Angiotensin-Converting Enzyme Inhibitor or Angiotensin-Receptor Blocker for Preventing Atrial Fibrillation Recurrence After Catheter Ablation: A Systematic Review and Meta-Analysis
Authors: FERNANDO BEZERRA, Clara Rocha Dantas, Luis Sobreira, Vitor Kendi Tsuchiya Sano, Artur de Oliveira Macena Lobo, Jorge Cardoso, Francinny Kelly, Francisco Cezar A de Moraes, Fernanda Colombo
Journal: Circulation (2024)

Introduction: In patients who have undergone catheter ablation due to atrial fibrillation (AF), recurrence of this condition can occur. The effect of Sacubitril/Valsartan (S/V) on preventing atrial fibrillation recurrence compared to Angiotensin-Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Blocker (ARB) is not established. This meta-analysis aims to establish the best therapeutic choice for preventing AF recurrence after catheter ablation. Method: A systematic search was conducted in PubMed, Embase, and Cochrane databases for randomized clinical trial (RCT) and observational studies comparing the use of S/V with ACEI/ARB in patients who underwent catheter ablation. Results were presented as mean differences (MD) with a 95% confidence interval (CI). Heterogeneity was assessed by I2, and outcomes were expressed as relative risks (RR), using R software version 4.2.3. Results: Three randomized clinical trials and one cohort study, comprising 642 patients with 319 patients in the S/V group and 323 in the control group, were included. Follow-up ranged from 6 to 36 months, with mean ages ranging from 58.9 to 65.8 years. A significant reduction in persistent AF occurrence was demonstrated favoring the S/V group (RR: 0.54; 95% CI: 0.41 to 0.70; P=0.000004; I2: 80%) compared to the ACEI/ARB group. The analysis also showed a significant reduction in Left Atrial Volume Index (LAVI) (MD: -5.33; 95% CI: -8.76 to -1.90; P=0.002; I2: 57%) in the S/V group compared to ACEI/ARB. There was no significant difference in left ventricular ejection fraction (LVEF) with S/V use (MD: 1.23; 95% CI: -0.12 to 2.60; P=0.076; I2: 0%) compared to ACEI/ARB. Conclusion: This meta-analysis demonstrated the efficacy of S/V in reducing the incidence of AF in patients undergoing catheter ablation compared to the use of ACEI/ARB. However, more randomized clinical trials are needed for a comprehensive evaluation of its efficacy in reducing AF recurrence in post-catheter ablation patients in clinical practice.
Abstract 4143095: Rural-Urban Disparities in Heart Transplant Outcomes for Heart Failure Patients: An Analysis of the National Inpatient Sample Dataset
Authors: Chinenye Odo, Toluwalase Awoyemi, Ikenna Odoh, Oluwaremilekun Tolu-Akinnawo, Kayode Ogunniyi, Rocio Barriga Guzman, Francis Ezekwueme, Habib Alagbo, Anderson Anuforo, Ugochukwu Ebubechukwu
Journal: Circulation (2024)

Background: Disparities in healthcare outcomes between rural and urban populations are well-documented, yet limited research specifically addresses differences in heart transplant outcomes for heart failure patients. Methods: We conducted a retrospective cohort study using the NIS dataset (2017-2020), analyzing 11,025 heart failure patients who received heart transplants. The cohort included 565 rural and 10,460 urban patients. We examined variables such as age, gender, hospital bed size, race, insurance status, and comorbidities. Primary outcomes included in-hospital mortality, mechanical ventilation requirement, length of stay, hospital charges, and vasopressor requirement. Multivariate logistic regression was performed to identify independent predictors of in-hospital mortality. Results: Age was found to be a significant predictor, with each additional year increasing the risk of mortality (OR 1.026, 95% CI 1.017-1.034, p &lt; 0.0001). Hospital bed size also played a critical role; patients in small hospitals had a significantly higher risk of mortality compared to those in large hospitals (OR 3.309, 95% CI 2.101-5.212, p &lt; 0.0001), whereas patients in medium-sized hospitals had a lower risk (OR 0.374, 95% CI 0.236-0.592, p &lt; 0.0001). While rural residency was associated with a higher mortality risk compared to urban residency, this association was not statistically significant (OR 1.40, 95% CI 0.95-2.07, p = 0.0860). Other factors, including the adjusted odds of vasopressor requirement (OR 1.13, 95% CI 0.92-1.39, p = 0.2524), need for mechanical ventilation (OR 1.12, 95% CI 0.87-1.43, p = 0.3741), length of stay (difference -0.005, 95% CI -8.57-1.33, p = 0.1709), and pacemaker insertion (OR 0.81, 95% CI 0.65-1.01, p = 0.062), did not show significant differences between groups. Conclusion: This study reveals that clinical outcomes post-heart transplant are comparable between patients in rural and urban settings. However, age and hospital bed size significantly influence mortality risk, with older age and treatment in smaller hospitals associated with higher mortality rates.
Abstract 4143094: COVID-19 Infection Had Significant Impact on In-Hospital Outcomes of Women with Peripartum Cardiomyopathy
Authors: Megan Pattoli, Spandan Desai, Nicholas Roma, Luke Miller, Lindsey Magid, Eluwana Amaratunga, Jamshid Shirani
Journal: Circulation (2024)

Background: Peripartum cardiomyopathy (PPCM) is defined as a dilated form of cardiomyopathy that occurs within the last month of pregnancy and up to 5 months postpartum. The etiology is likely multifactorial and viral infections may account for up to a third of PPCM cases. We aimed to examine the impact of concurrent COVID-19 infection on in-hospital outcomes of women with PPCM. Methods: National Inpatient Sample was queried to identify women admitted with PPCM with COVID-19 (group A) between the years 2020-2021 and without (group B) concurrent COVID-19 infection between the years 2016-2019. Results: A total of 19135 women were admitted with PPCM between the years 2016-2021, of whom 420 (2%) had concurrent COVID-19 infection. Group A PPCM followed a seasonal pattern with peak incidence in fall (43%) followed by winter (31%), spring (13%) and summer (13%) [p=0.002]. Group A was more often Hispanic (20.3% -vs- 10.8%, p&lt;0.001) and more often admitted to urban teaching hospitals (88.1% -vs- 79.7%, p&lt;0.001), had longer length of stay (9.7 -vs- 5.8 days), and overall greater cost of hospitalization ($162181 -vs- $92155). Group A also had greater rates of acute myocardial infarction (11.9% -vs- 5.6%, p&lt;0.001), bleeding requiring transfusion (8.3% -vs- 5.4%, p=0.030), pulmonary embolism (4.8% -vs- 2.4%, p=0.057), shock (14.3% -vs- 3.1%, p&lt;0.001), ICU admission (29.8% -vs- 10.2%, p&lt;0.001), vasopressor requirement (10.7% -vs- 2.1%, p&lt;0.001), ventilator requirement (27.4% -vs- 9.1%, p&lt;0.001), and cardiopulmonary resuscitation (7.1% -vs- 1.1%, p=0.005). Overall in-hospital mortality was also higher in group A (8.3% -vs- 1.5%, p&lt;0.001). Conclusion: PPCM appeared to follow a seasonal trend in incidence similar to COVID-19. COVID-19 infection may have accounted for some cases of PPCM and was associated with adverse in-hospital outcomes and higher mortality.
Abstract 4143137: Lets talk about sex: update on sexual health and information need of persons with a cardiac illness.
Authors: Tiny Jaarsma, Leonie Klompstra, Tommy Persson, Elin Klingvall, Anna Skoglund, Frida Saren
Journal: Circulation (2024)

Background: Sexual health is an important aspect of quality of life, regardless of cardiac disease. However, there is a significant gap between patients' information needs and the ability of the healthcare system to meet these. Most studies focus on clinical populations in specialized clinics, but data on sexual health and information needs among community based cardiac patients is scarce. Method: We conducted an online national survey in Sweden in 2024. The survey was developed based on literature and previous international surveys on sexual health in cardiac patients. Recruitment took place via patient organizations, clinical outpatient departments and via social media. All data was collected anonymously. Results: In total 135 persons (59% male, mean age 65, range 30-89) answered the survey, 47% had hypertension, 36% had a myocardial infarction, 30% atrial fibrillation, 24% heart failure. In total 76% stated that their sexual health was impacted by their disease and affects their mood and well-being (n=102). Men more often than women thought their disease impacted their sexual health (65% vs. 35%, p=0.02) and more often that sexual health affected their mood and well-being (64% vs. 36%, p&lt;0.01). Only 5% received sexual health information, but 78% wanted it. Men more often expressed a desire for information compared to women (87% vs. 64%, p=0.02). The most desired topics include medication side effects (60%, n=81), erectile dysfunction (50%. n=68), impact on relationships (47%, n=63) and anxiety before sex (35%, n=47). Men wanted information on erectile dysfunction (80% vs. 7%), and women wanted more often information on pain during sex (13% vs. 1%, p&lt;0.01). Patients prefer to receive information during annual check-ups (57%, n=77), and/or during diagnosis (51%, n=69), and/or during medication follow-ups (40%), n=54. Patients most favor conversations with healthcare professionals (79%) and/or getting information at various times from different sources (43%). Conclusion: This study highlights a significant gap between patients’ needs for sexual health information and the actual support provided by the healthcare system. Despite 76% of patients reporting that sexual health affects their mood and well-being, only 5% received relevant information or counseling. The study underscores the importance of structual policy changes addressing sexual health concerns in cardiac patients.
Abstract 4143140: Pregnancy Termination or Perinatal Hospice due to Fetal Congenital Heart Defects: A Qualitative Analysis
Authors: Grace Knowles, Diana Madden, Leonardo Barrera, Jessica Fry, William Grobman, Natalia Henner, Angira Patel, sheetal patel, Lynn Yee, Joyce Woo
Journal: Circulation (2024)

Background: For some individuals, antenatal diagnosis of a congenital heart defect (CHD) allows alternative options to cardiac surgery: pregnancy termination or perinatal hospice care. Understanding drivers of decision-making for these two non-surgical options is critical to guide patient-centered counseling practices. We aimed to explore experiences and decision-making among individuals who chose termination or perinatal hospice care after diagnosis of a fetal CHD. Methods: This was a qualitative analysis of semi-structured, 1:1 interviews with birthing individuals or their partners from a purposive sample of those who experienced termination or perinatal hospice after receiving multidisciplinary counseling for severe fetal CHD at Lurie Children’s between 2019-2022. The interview guide was comprised of open-ended questions addressing counseling experiences, decision making, and for relevant participants, postnatal experience with perinatal hospice care. The guide was designed by fetal cardiologists, maternal-fetal medicine specialists, neonatologists, palliative care specialists, qualitative researchers, an ethicist, and two parent advisors. Interviews (60-90 minutes) were professionally transcribed and analyzed using Dedoose software. Thematic analysis was conducted with an inductive approach. Results: In total, 20 pregnant individuals and their partners met inclusion criteria and were asked to participate. Of these, 10 completed interviews, 9 carried fetuses with single ventricle disease, 2 experienced perinatal hospice care, and 8 identified as non-Hispanic White ethnicity/race. Themes included variability in antenatal counseling, value for reproductive justice, life factors considered in decision-making, and successful aspects of perinatal hospice (Table). Conclusion: Among individuals who experienced termination or perinatal hospice due to fetal CHD, there is significant variability in the experiences with counseling. Yet, there is shared value for provider support, consideration for life factors in decision-making, and reproductive autonomy. Understanding both the variability and shared themes is key to optimize and standardize counseling practices for fetal CHD.
Abstract 4143153: Correlation Between CRT Response and Patient-Reported Outcomes in Heart Failure with Reduced Ejection Fraction Patients
Authors: Aritra Paul, Joe Demian, Niraj Varma, J. Emanuel Finet, Arshneel Kochar, Feras Bader, Oussama Wazni, Wilson Tang, John Rickard
Journal: Circulation (2024)

Background: The correlation between CRT response and patient-reported outcomes is uncertain. Objective: To identify whether patient reported outcomes correlate with CRT response through a decision regret scale (DRS) in patients with heart failure with reduced ejection fraction (HFrEF). Hypothesis: CRT non-responders have more regret over having undergone device implant compared with responders. Methods: We included a total of 150 patients with HFrEF who underwent CRT implantation at the Cleveland Clinic from 2020-2022. Each patient was given a DRS questionnaire at 6 months post-CRT implant, and their CRT response status was assessed echocardiographically. Response was defined as an improvement in LVEF &gt;5% with reduction in LVESV&gt;10%. Patients were unaware of their response status at the time of filling out the questionnaire. The DRS Questionnaire asks patients whether they regret their decision to undergo a procedure. Patients rated, on a scale of 1 (strongly agree) to 5 (strongly disagree)- their agreement with five statements: It was the right decision; I regret the choice that I made; I would go for the same choice again; The choice did me a lot of harm; and The decision was a wise one. We grouped questions 1,3, and 5 from the DRS together for positive score (higher is more regret), and questions 2 and 4 were grouped together for negative score (lower is more regret). This data was compared between 2 groups based on responder (107; 71.33%) and non-responder status (43; 28.67%). Results: The median IQR positive score and negative score among all patients was 3 (3-5), and 10 (8-10) respectively. There were no patients who voiced significant regret for having undergone device implant. In comparing the scores between responders and non-responders, the Mann-Whitney U test revealed no difference in scores. [Median IQR positive score 3 (3-6) in non-responders, 3 (3-4.5) in responders; p=0.19; negative score 10 (8-10) non-responders,10 (9-10) in responders; p=0.44] (Figure 1). Conclusion: Patients with HFrEF undergoing CRT overwhelmingly do not regret their decision to undergo device implantation. The presence or absence of significant remodeling had no impact on patient satisfaction feelings towards the decision to undergo device implantation.
Abstract 4143142: Lost to Follow Up: A Rare Case of Malonyl-CoA Decarboxylase Deficiency Induced Cardiomyopathy in an Adult Spanish Speaking Hispanic Male
Authors: Reniell Iniguez, Jessica Quaggin-Smith, Sarah Hale, Jane Wilcox
Journal: Circulation (2024)

Introduction: Malonyl-CoA decarboxylase deficiency (MLYCDD) is a rare inherited metabolic disorder with multi-organ involvement, causing cognitive impairment, cardiomyopathy, seizures, hypotonia, and acidosis. Variants in MLYCCD, the gene for malonyl-CoA decarboxylase, disrupt long chain fatty acid synthesis in cardiac tissue. Prevalence is estimated to be less than 1 in 1,000,000, with cardiomyopathy being the leading cause of morbidity and mortality. Less than 40 cases have been documented, the majority of which detail newborns. No guidelines exist for treatment. A high-carbohydrate, low-fat diet, and levocarnitine reportedly improve cardiac function. Presentation: A 30-year-old Spanish-speaking male with MLYCDD, with resultant heart failure with reduced ejection fraction (EF) and cognitive delay, presented to a community hospital with malaise. He was diagnosed at age 9 and followed with an interdisciplinary team, receiving care in Spanish and English since diagnosis. His treatment consisted of levocarnitine and dietary restrictions that had led to cardiac recovery. At 24, his doctor retired, his insurance changed, and he was lost to follow-up, leading to dietary liberalization. On presentation, he was diagnosed with pneumonia complicated by atrial fibrillation (AF). AF was treated with a diltiazem infusion, resulting in cardiogenic shock with an EF of 15% from 39%. He was transferred to an academic center where diltiazem was stopped, inotropes started, and impella placed. He started enteral nutrition with liquid protein, dextrose infusion, medium-chain triglyceride (MCT) oil, and levocarnitine, along with supportive care for pneumonia. Given persistent shock he was transferred to our center for advanced therapies evaluation. Notable changes included replacing MCT oil with triheptanoin and stopping the dextrose infusion. A repeat echocardiogram showed recovery of EF to 40% Conclusions: MLYCDD exhibits a range of phenotypes, with limited data on long-term outcomes. This presentation is atypical: an adult with cardiomyopathy diagnosed in adolescence, successfully treated, who decompensated after stopping a modified diet in the setting of pneumonia and diltiazem. This case offers several clinical insights: (1) Restrictive diets with levocarnitine supplementation are instrumental in treating MLYCDD. (2) Avoid diltiazem in heart failure to prevent iatrogenic shock. (3) Language-concordant care ensures patients understanding and supports seamless care transitions.
Abstract 4143071: Comparative outcomes of cardiac arrest survivors with and without the use of neuromuscular blockers.
Authors: Abhishek Dutta, Krunalkumar Patel, Avilash Mondal, Smriti Bhatia, Ramy Doss, Chaudry Majeed, Waqas Qureshi, Sunil Dhar
Journal: Circulation (2024)

Introduction: Cardiac arrests result in significant mortality and morbidity, with therapeutic hypothermia (TH) being a mainstay in post-cardiac arrest care to enhance neurological outcomes. The use of neuromuscular blockade (NMB) agents with TH aims to manage shivering, ventilator asynchrony, and reduce cerebral oxygen demand. However with recent studies showing normothermia to be effective in achieving good neurological outcomes, the use of these agents remains debatable.This study investigates the comparative outcomes of cardiac arrest survivors with and without the use of NMB agents. Methods: A retrospective cohort study was conducted at a tertiary care hospital in North Carolina involving 4047 patients with cardiac arrest from 01/01/2012, to 12/12/2017. Adults surviving beyond 24 hours post-cardiac arrest were included, while those with a Glasgow Coma Scale ≥8, actively bleeding or pregnant patients were excluded. Demographic, comorbid variables and clinical outcomes were collected and analyzed to compare the efficacy of NMB use. We examined the 30 day mortality and neurological outcomes of both groups Results: Of total 976 patients, 364 (37.3%) received NMB agents.58.5% of patients received NMB as part of hypothermia protocol .Vasopressor use was also more in paralytic group (81.9% vs. 73.5%) p.004. There was no significant difference in 30-day (54.1% vs. 51.7%, p=0.45), 60-day (56.6% vs. 52.5%, p=0.2) mortality among two groups. The use of NMB agents was not associated with better neurological outcomes (66.2% vs 65.7%) Conclusion: The use of NMB agents in cardiac arrest survivors did not improve survival or neurological outcomes regardless of their use with or without therapeutic hypothermia. Compared to previous studies, our study did not find NMB agents to be superior. Further studies are needed to delienate the specific contexts when the use of NMB agents may be beneficial.