tbuckley/cabot-search huggingface dataset:
Abstract 4135301: Cardiac specific gene therapy to treat diabetic heart failure with preserved ejection fraction
Authors: Yugene Guo, Hong Liu, Gyeoung-Jin Kang, Man Liu, Jonah Butler, Samuel Dudley
Journal: Circulation (2024)

Background: We have previously demonstrated that diabetes mellitus (DM) causes cardiac inflammation leading to heart failure with preserved ejection fraction (HFpEF). Arachidonate 5-lipoxygenase (5-LOX), encoded by the ALOX5 gene, is an enzyme that is highly expressed in leukocytes. 5-LOX synthesizes specialized pro-resolving mediators (SPMs) including Resolvin D1 (RvD1), which reduce inflammation. Hypothesis: We hypothesize that cardiac-specific ALOX5 upregulation could prevent diabetes-associated HFpEF without inducing systemic immunosuppression. Methods: DM was induced by feeding mice with a high fat diet (HFD, 60% fat by kcal) starting from 6 weeks of age for 22-24 weeks. At 24 weeks of age, DM mice were treated with RvD1, by intraperitoneal injection at 100 ng/mouse for 2 weeks. To specifically upregulate 5-LOX in the heart, another cohort of DM mice were injected with either AAV9-plain or AAV9- ALOX5 viral vectors under the control of the α-myosin heavy chain (MHC) at 22 weeks old. At 28 weeks, we performed echocardiographic measurement of diastolic function and heart extraction. Results: HFD-induced DM mice showed lower cardiac 5-LOX expression (0.72 ± 0.05 a.u. vs. 1.09 ± 0.12, p &lt; 0.05) and RvD1 levels (1 ± 0.08 vs. 1.9 ± 0.14 fold change over DM mice, p&lt;0.0001) than the mice with normal diet. RvD1 treatment significantly improved DM-associated diastolic function (19.7 ± 1.4 a.u. vs. 22.9 ± 0.4, p&lt;0.05). With cardiac specific upregulation of 5-LOX, cardiac 5-LOX expression (0.89 ± 0.06 vs. 0.70 ± 0.04 a.u., p&lt;0.05) and RvD1 levels were increased (2.1 ± 0.3 a.u. vs. 1.2 ± 0.2, normalized to AAV9-plain, p&lt;0.05). AAV9- ALOX5 also reduced NLRP3 inflammasome activity (0.80 ± 0.02 a.u. vs. 0.90 ± 0.02, p&lt;0.01) and improved DM-associated diastolic dysfunction (17.0 ± 1.2 a.u. vs. 20.5 ± 1.0, p&lt;0.05) without affecting glucose metabolism and obesity in DM mice. Moreover, no alterations of cardiac macrophage infiltration, inflammatory IL1β signaling, or macrophage phenotype were observed in response to cardiac-specific ALOX5 upregulation. Conclusion: In conclusion, both direct RvD1 treatment and cardiac-specific gene therapy to enhance resolution of inflammation in cardiomyocytes reversed DM-associated HFpEF. Gene therapy avoided off-target immunosuppression. Therefore, AAV-directed cardiac ALOX5 upregulation represents a novel cardiac-specific gene therapy for HFpEF that avoids systemic immunosuppression.
Abstract 4135270: Clinical and Procedural Outcomes after Transcatheter Aortic Valve Replacement vs Surgical Aortic Valve Replacement in Severe Aortic Stenosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Aqsa Shoaib, Ayesha Ali Khan, Muhammad Khan, Iqra Khan, Muhammad Hammad Arif, Ahson Afzal, Neha Mohiuddin, Tariq Jamal Siddiqi
Journal: Circulation (2024)

Introduction: A growing body of evidence from randomized controlled trials (RCTs) has demonstrated the superiority of transcatheter aortic valve replacement (TAVR) over surgical aortic valve replacement (SAVR) irrespective of surgical risk in patients with severe aortic stenosis (SAS). Given the rise in TAVR procedures, analyzing trends in outcomes over time is critical to aid clinical decision-making. Hence, we pooled RCT data for a robust assessment of clinical and procedural outcomes in SAS patients undergoing TAVR and SAVR. Methods: PUBMED and SCOPUS were queried until April 2024. Trials were classified into high and low-risk groups based on surgical risk. The outcomes were analyzed at 30 days (short-term), 1 year (mid-term), and 5 years (long-term). Estimates were calculated as random effects risk ratios (RRs) with 95% confidence intervals (CI). Results: 10 RCTs with a total of 10,252 patients were included. There was no significant association between TAVR and SAVR in reducing all-cause mortality at 30 days (RR: 0.84 [0.64, 1.10]; Figure 1a). While TAVR was associated with a significantly lower all-cause mortality at 1 year (RR: 0.82 [0.68-0.97]; Figure 1b), it was linked with a significantly higher all-cause mortality at 5 years (RR: 1.14 [1.07-1.21]; Figure 1c). Myocardial infarction and stroke were similar in both groups up to 5 years. TAVR was associated with a lower risk of acute kidney injury for up to 1 year and atrial fibrillation for up to 5 years but a higher risk of new permanent pacemaker implantation and aortic valve re-intervention for up to 5 years. In low-risk patients, TAVR showed no significant differences from SAVR for all-cause mortality at 30 days and 5 years, but it was significant at 1 year. In high-surgical-risk patients, all-cause mortality was comparable between TAVR AND SAVR at 30 days and 1 year, with a higher rate observed with TAVR at 5 years. Conclusion: Compared with SAVR, TAVR was superior in reducing all-cause mortality at 1 year in low-risk patients and inferior in reducing all-cause mortality at 5 years in high-risk patients. A thorough evaluation of anatomical, clinical, and procedural factors is crucial to tailor the optimal intervention for each patient.
Abstract 4135265: When the Beat Drops: A Pilot Project for a Case-Based Resident’s Guide to Cardiovascular Care
Authors: Rebecca Garber, Satish Mishra
Journal: Circulation (2024)

Residents care for patients with a vast array of cardiovascular (CV) diagnoses in settings ranging from primary care clinic to the cardiac intensive care unit. However, the resources available are mainly intended for advanced cardiology trainees. We created a resident-driven, case-based reference for residents to serve as a companion to traditional CV medicine educational resources. Methods: We surveyed residents, fellows, and cardiology attendings to identify topics within CV care for which residents are responsible. We recruited residents from multiple ACGME-accredited Internal Medicine residency programs to write a chapter on each identified topic that would be published on a central website. The chapters included a topic overview with key learning points, a case presentation, review questions, attending pearls, and high-yield articles for further reading. Chapters were reviewed for accuracy and completeness by cardiology fellows, pharmacologists, and attendings. The chapters were sent out to residents weekly via email and through social media platforms. Website analytics were used to track usage and monitor engagement. Each chapter concluded with a brief survey regarding learning gains, comprehension, and if the reader would recommend the resources to others. Results: A total of 52 cases were submitted by resident contributors from four residency programs. Topics included management of arrhythmias, structural heart disease, ischemia, cardiogenic shock, and post-procedure complications. Within the first two months of publication, the website was being accessed throughout 30+ states and 6 countries with more than 2,500 views and 1,500 unique visitors. Topics with high traffic included chapters regarding arrhythmias and post-procedural complications. The website was viewed throughout the entire day with no specific time pattern; however, there were significantly more views on days when each chapter was released via email and social media. Preliminary survey results show that residents and other trainees find this resource useful, and many want to get involved and help create more content. Conclusion: Our resident-created and cardiologist reviewed website is a unique resource created for residents caring for patients with CV disease. Using email and social media marketing has allowed this resource to be widely accessible to a large global audience. Survey feedback suggests the importance of this resource and need for continued CV resources for trainees.
Abstract 4135279: The Watchman Device needs to be Watched: A Case of Device Related Thrombus
Authors: Sameer Acharya, Bryan Fiema, ali akram, Jeremiah Depta
Journal: Circulation (2024)

Introduction: Left atrial appendage (LAA) harbors approximately 90% of thrombi in non-valvular atrial fibrillation (AF) for which an anticoagulant (AC) is indicated to prevent cardio-embolic stroke. Alternatively, the benefits of LAA occlusion (LAAO) devices to those patients who encounter life-threating bleeding with AC are also well established. However, the LAAO device comes with the risk of device related thrombus (DRT), which is a real challenge. Case: A 68 year-old-male with history of chronic AF on apixaban and recurrent ischemic and hemorrhagic stroke was evaluated for LAAO device placement procedure. Initially, when the patient was not taking AC, he had an ischemic stroke likely cardio-embolic source, which necessitated the initiation of apixaban. Unfortunately, while he was taking apixaban, he had a right thalamic bleed causing persistent left sided paresis. Subsequently, AC was held for 6 months and he underwent watchman device placement. He remained on apixaban for 45 days post procedure and was continued on aspirin only. After 10 months, on routine cardiac computerized tomographic arteriography (CTA), a large filling defect measuring 1.7 x 1.4 cm on the left atrial side of the watchman device was seen (Figure 1A) which was confirmed with transesophageal echocardiogram. Then, he was re-started on apixaban for a short period of time, which culminated him to have a right temporal bleed. After holding AC for 3 months, repeat CTA showed persistent filling defect suggestive of DRT (Figure 1B). Therefore, AC was permanently discontinued and patient was evaluated for DRT removal procedure. Utilizing a shared decision model, the option of mechanical thrombectomy with cerebral protection device (CPD) was chosen to mitigate the risk of embolic stroke. Post procedure, he was continued on apixaban 2.5 mg twice daily for 3 months and then aspirin forever. Subsequent surveillance CTA did not show DRT (Figures 1C and D). Patient has remained asymptomatic thereafter. Conclusion: 3-7% of patients with Watchman device suffer from DRT. Life threatening bleeding from AC further complicates the management of such patients. Mechanical thrombectomy with CPD is an established procedure for the removal of intra-arterial or intravenous thrombus. However, the feasibility of the routine use of mechanical thrombectomy with CPD for persistent DRT in-patient like ours is yet to be studied in detail.
Abstract 4135286: Comparative Efficacy of Intracardiac and Transesophageal Echocardiography in Left Atrial Appendage Occlusion: A Meta-Analysis of Clinical Outcomes
Authors: Sudeep Nugooru, Shravya Ginnaram, Prerana Sevella, Chaitra Janga, Enad Haddad, Shreeja Shah, Robert Watson
Journal: Circulation (2024)

Background: Left atrial appendage occlusion (LAAO) is essential for stroke prevention in patients with non-valvular atrial fibrillation where anticoagulation is contraindicated. Intracardiac Echocardiography (ICE) has been proven effective and safe for LAAO since 2011, yet adoption rates remain low, with only 2.2% of LAAOs guided by ICE between 2015 and 2019. Transesophageal Echocardiography (TEE), the current gold standard, and ICE differ significantly in operational dynamics and patient impacts, influencing procedural outcomes. Objective: This study aims to compare the efficacy and safety of ICE and TEE in facilitating LAAO, offering insights into their comparative clinical use. Methods: A systematic review and meta-analysis were conducted according to PRISMA guidelines. Searches were performed in MEDLINE/PubMed, OVID, and Scopus through December 2023, comparing ICE and TEE in LAAO. Inclusion criteria centered on studies reporting technical success, with secondary outcomes including length of stay (LOS), mortality, and adverse outcomes such as stroke, transient ischemic attacks (TIA), pericardial effusion, cardiac tamponade, device thrombosis, device embolization, and peri-device leaks. Data synthesis employed statistical methods utilizing R Studio. Results: Fourteen studies involving 4184 patients were included. The meta-analysis revealed no significant differences in technical success (OR 1.34, 95% CI: [0.76, 2.36]), LOS (OR 1.66, 95% CI: [0.80, 3.42]), or mortality (OR = 1.00, 95% CI: [0.50, 2.00]) between ICE and TEE. Similarly, non-significant differences were noted in stroke, TIA, pericardial effusion, and device leaks, with minimal heterogeneity (I 2 = 0%). Conclusion: ICE and TEE provide comparable clinical outcomes in LAAO, with no significant efficacy or safety differences. These results suggest that the choice between ICE and TEE should be based on procedural convenience, patient anatomy, and resource availability, rather than clinical outcomes alone. The equivalence in performance between these modalities allows for flexibility in clinical practice, ensuring that patient care can be customized to individual needs without compromising safety or effectiveness.
Abstract 4135303: Acute Pericarditis Secondary to Secukinumab Therapy
Authors: Aakriti Jain, Sahej Arora, Hafsa Jawaid, asmaa ahmed, Muhammad Hammad Sharif, BASIL VERGHESE, BIPUL BAIBHAV
Journal: Circulation (2024)

Background: Pericarditis is the most common pericardial disease worldwide and has a high recurrence rate of 15-30%. It is primarily idiopathic but can arise from infectious and non-infectious causes; drug related cases are rare. Secukinumab, a fully human anti-interleukin-17A monoclonal antibody used for treating psoriasis, has been identified through the FDA Adverse Event Reporting System as potentially inducing pericarditis, though literature is scant. We report a case of acute pericarditis related to secukinumab use. Case presentation: A 28-year-old male with history of psoriasis on secukinumab therapy presented with sharp, central chest pain, and progressive shortness of breath for 3 weeks. He was evaluated for similar chest pain 3 weeks prior; CT chest showed small pericardial effusion and he was managed with analgesics without improvement. This admission, he had tachycardia, and ECG showed sinus rhythm with diffuse ST elevation and PR depression (Figure 1A). Troponin I levels were normal and inflammatory markers were elevated. Transthoracic echocardiogram (TTE) revealed a large pericardial effusion without tamponade physiology (Figure 1B). CT chest confirmed large pericardial effusion, increased in size compared to CT done 3 weeks prior (Figure 2). He was diagnosed with pericarditis and started on ibuprofen and colchicine which improved his symptoms. Search for viral etiology including testing for COVID, influenza A and B, RSV, hepatitis and HIV were negative. Immunological workup for ANA and rheumatoid factor was negative. Thus, secukinumab was thought to be the likely culprit. Follow-up TTE in 3 months showed resolution of pericardial effusion. Conclusion: This case underscores the importance of considering medication-induced pericarditis in patients presenting with typical symptoms, especially when on treatment with drugs like secukinumab. Given the growing evidence from pharmacovigilance databases and the severe potential outcomes of untreated pericarditis, clinicians should maintain vigilance for such adverse effects. Further research is warranted to clarify the mechanisms by which secukinumab may contribute to pericardial inflammation in order to optimize management strategies in affected patients.
Abstract 4135252: Associations between Group 2 Pulmonary Hypertension and 30-Day Readmissions Following Acute Myocardial Infarction Hospitalizations.
Authors: nadhem abdallah, Abdilahi Mohamoud, Meriam Abdallah
Journal: Circulation (2024)

Background: Pulmonary hypertension (PH) is a major contributor to cardiovascular disease-related morbidity and mortality. Despite this, little is known regarding the outcomes of 30-day re-admissions following Acute Myocardial Infarction (AMI) in the context of group 2 PH. Hypothesis: Group 2 PH is associated with a higher likelihood of 30-day readmissions in patients presenting with AMI. Goal: To assess the relationship between group 2 PH and adverse hospitalization outcomes in cases of AMI. Methods: We queried the 2016-2020 Nationwide Readmission Database (NRD) and identified AMI as the primary diagnosis. We compared in-hospital outcomes based on the presence versus absence of Group 2 PH. The primary outcome was 30-day readmissions. Secondary outcomes included the odds of in-patient mortality, mechanical ventilation use, vasopressor use, and mechanical circulatory support (MCS) use. Multivariable regression models were used to adjust for confounders. Results: Among 182,308 AMI hospitalizations, 364 (0.2%) had a secondary diagnosis of Group 2 PH. Group 2 PH was associated with a higher likelihood of re-admission within 30 days (adjusted OR [aOR] 1.21, 95% CI 1.07–1.36, p=0.002). Additionally among patients presenting with AMI, group 2 PH was associated with higher odds of in-patient mortality (aOR 2.64, 95% CI 1.52–4.58, p=0.001), mechanical ventilation use (aOR 2.07, 95% CI 1.19–3.6, p=0.010), vasopressor use (aOR 5.4, 95% CI 2.7-10.9, p&lt;0.001) and MCS use (aOR 2.39, 95% CI 1.46-3.91, p&lt;0.001) during index hospitalization compared to the patients without group 2 PH. Conclusion: Patients with Group 2 PH admitted for AMI had higher odds of 30-day readmissions and both fatal and non-fatal adverse outcomes compared to patients without PH. Further studies are needed to confirm these findings and develop strategies to improve outcomes for this high-risk population.
Abstract 4135281: Bidirectional Associations of Chronic Kidney Disease and Heart Failure are Frequent and Associated with Higher Mortality: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Shengyuan Luo, Sui Zhang, Justin Echouffo, VIJAY NAMBI, Christie Ballantyne, Amil Shah, Anum Minhas, Kuni Matsushita, Morgan Grams, Elizabeth Selvin, Joe Coresh, Chiadi Ndumele
Journal: Circulation (2024)

Background: Chronic kidney disease (CKD) and heart failure (HF) are interrelated but the bidirectional associations between the two conditions are not completely understood. Hypothesis: Bidirectional associations between CKD and HF are common in ambulatory populations and have implications for survival. Methods: We conducted a prospective cohort study of 11595 participants who attended ARIC Visit 4 (1996-98) with data on prevalent CKD and HF status, with follow-up for incident events through 2021. We assessed the prospective association of prevalent CKD (defined as eGFR&lt;60 ml/min per 1.73 m 2 or urine albumin-creatinine ratio of ≥30 mg/g) at Visit 4 with incident HF. We also assessed the association of prevalent HF at Visit 4 with incident CKD through 2019. Analyses accounted for mortality as a competing risk. We cross-categorized CKD and HF at Visit 4 and assessed prospective associations with mortality relative to those with neither condition. Results: The mean age in the study population was 63 years, with 56% women; and 23% Black adults. Among 1222 with prevalent CKD, 529 (43%) developed HF; among 433 with prevalent HF, 137 (31%) developed CKD. After multivariable adjustment, prevalent CKD (vs no CKD) was associated with incident HF (HR 1.87; 95% CI, 1.65–2.12; Figure ). Prevalent HF (vs no HF) was also associated with incident CKD (HR 1.33; 95% CI, 1.09–1.62). The co-occurrence of prevalent CKD and HF was associated with greater mortality risk (HR, 2.07; 95% CI, 1.78–2.42) than prevalent CKD alone (HR, 1.47; 95% CI, 1.37–1.59) or prevalent HF alone (HR, 1.33; 95% CI, 1.18–1.50), when compared with neither condition ( p interaction &lt;0.001). Conclusions: Bidirectional associations between CKD and HF are common in ambulatory populations. The co-existence of both CKD and HF is associated with higher mortality compared to either alone. There is a need to refine strategies to mitigate risk associated with bidirectional CKD and HF associations.
Abstract 4135259: Coronary Artery Anomalies Induce Myocardial Ischemia in Hypertrophic Cardiomyopathy
Authors: Luke Miller, Yaniv Maddahi, Nicholas Roma, Megan Pattoli, Jamshid Shirani
Journal: Circulation (2024)

Background: Myocardial ischemia is a frequent finding in hypertrophic cardiomyopathy (HCM) and is often attributed to microvascular disease, extravascular compressive forces, reduced coronary flow reserve, hemodynamic abnormalities, and concomitant atherosclerotic coronary artery disease (CAD). The potential contribution of congenital coronary artery anomaly (CCAA) to myocardial ischemia in HCM has not been systematically explored. Research Question: We aimed to evaluate the spectrum and potential contribution of CCAA to myocardial ischemia in HCM. Methods: From June 1991 to March 2023 a total of 35 CCAA were reported in 29 adults [age 18-87 (47.9±19.9; 59% male; 35% obstructive, 21% apical variant). Clinical data on presence or absence of myocardial ischemia, mode of therapy, and outcomes of the patients were reviewed. Results: The individual CCAAs were graphically reproduced [Figure] and were categorized based on the number of coronary ostia present in the aorta [single ostium (n=11; 38%); 2 ostia (n=13; 45%); 3 ostia (n=4; 14%); 4 ostia (n=1; 3%)]. The anomalous coronary artery was the left main in 6 (17%); left anterior descending in 6 (17%); left circumflex in 8 (23%); right in 14 (40%) or the ramus intermedius in 1 (3%). Two patients (7%) with apical variant HCM also had coronary artery fistulae in a non-anomalous coronary artery. Of all 29 patients who presented, 12 (41%) showed objective evidence of myocardial ischemia and of those, a total of 6 (50%) had an anomalous coronary artery coursing between the great vessels. In addition, 1 of 5 patients with sudden cardiac arrest had a high-risk coronary anomaly. Pharmacologic treatment was offered to 11 (38%) patients and 3 (10%) patients underwent coronary artery surgery (bypass grafting in 2 and unroofing in 1). Septal reduction therapy was performed in 8 (28%). Follow up data was available in 14 patients including 2 of the 3 who underwent surgical correction. Symptomatic improvement was noted in all 14. Conclusion: Congenital coronary artery anomalies may be present in patients with HCM and may contribute to myocardial ischemia. Treatment options depend on the type of anomaly and presence of objective evidence of myocardial ischemia.
Growth hormone-releasing hormone and its analogues in health and disease
Authors: Riccarda Granata, Sheila Leone, Xianyang Zhang, Iacopo Gesmundo, Charlotte Steenblock, Renzhi Cai, Wei Sha, Ezio Ghigo, Joshua M Hare, Stefan R Bornstein, Andrew V Schally
Journal: Nature Reviews Endocrinology (2024)
Cardiorespiratory fitness, body mass index and mortality: a systematic review and meta-analysis
Authors: Nathan R Weeldreyer, Jeison C De Guzman, Craig Paterson, Jason D Allen, Glenn A Gaesser, Siddhartha S Angadi
Journal: British Journal of Sports Medicine (2024)

The purpose of this review was to assess the joint relationship of cardiorespiratory fitness (CRF) and Body Mass Index (BMI) on both cardiovascular disease (CVD) and all-cause mortality risk.