tbuckley/cabot-search huggingface dataset:
Abstract 15154: Therapeutic Effect of Optimal Medication on Biochemical Plaque Composition in Patients With Coronary Artery Disease as Serially Assessed by Intravascular Multi-Targeted Fluorescence Lifetime Imaging Fully Integrated With OCT
Authors: Dong Oh Kang, Hyeong Soo Nam, Sunwon Kim, Jeongmoo Han, Jin Hyuk Kim, Ryeong Hyun Kim, Hyun Jung Kim, Ye Hee Park, Hyokee Kim, Joon Woo Song, Eun Jin Park, Hongki Yoo, Jin Won Kim
Journal: Circulation (2023)

Introduction: Fluorescence lifetime imaging (FLIm) is an emerging technique that can visualize detailed molecular properties of atherosclerosis. We conducted an in vivo serial molecular characterization of human coronary plaques using a fully-integrated, dual-modal, intravascular optical coherence tomography-FLIm (OCT-FLIm) system to explore the natural history of biochemical plaque composition. Methods: We prospectively enrolled patients with significant coronary artery disease those who underwent 6-month serial OCT-FLIm assessment for non-culprit/non-target lesions. A non-culprit/non-target lesion was defined as medically-treated angiographic mild-to-moderate stenosis diagnosed at index procedure. Biochemical plaque compositions were categorized by FLIm-derived parameters using a dedicated machine learning classifier. Each lesion was quantitatively assessed for the pre-specified plaque compositions and compared with the serial images. Results: Total 53 non-culprit/non-target lesions from 30 patients were enrolled. Angiography- and OCT-defined lesion severity showed no significant difference over the follow-up (p&gt;0.05). Intriguingly, while the macrophage signal intensity decreased after 6 months (p=0.034), FLIm-based quantitative assessment revealed a worsened plaque compositional response by increased loose fibrous tissue (p=0.004) and decreased normal/fibrous tissue burden (p&lt;0.001). These temporal changes in individual plaque components correlated well with the achieved LDL-cholesterol level at 6-month (p&lt;0.05), whereas no correlation was found with hs-CRP (p&gt;0.05). Conclusion: From this comprehensive serial assessment of human coronary atheroma by intravascular OCT-FLIm, optimal medical therapy alone was insufficient to effectively stabilize plaque composition, and additional therapeutic strategy should be explored to alter the natural course of atherosclerosis from a molecular perspective.
Abstract 13306: Substantial Variation in the Rate of Coronary Artery Disease Among Ontario Immigrants
Authors: Hirmand Nouraei, Feng Qiu, Joan Porter, Mina Madan, Harindra C Wijeysundera, Baiju Shah, Maneesh Sud, Husam M Abdel-Qadir, Olivia Haldenby, Dennis T Ko
Journal: Circulation (2023)

Immigrants constitute a substantial proportion of the population in Western Europe and North America. Although prior studies have suggested that a "healthy immigrant effect" exists, little is known about the extent and variation of stable obstructive coronary artery disease (CAD) among immigrants. We evaluated the association of country of origin and the rates of stable CAD among immigrants. We assembled a cohort of immigrants and non-immigrants who received elective cardiac catheterization in Ontario, Canada, between April 1, 2012 and March 31, 2021. Immigrants were categorized by their country of origin into 7 regions: Africa, Caribbean, Latin America, Western Countries, East Asia, South Asia, and Middle East. Our main outcome was the rate of obstructive CAD (left main stenosis ≥50% or major epicardial vessel stenosis ≥70%). Multivariable logistic regression analyses adjusting for age, cardiac risk factors, and socioeconomic status was used to study the association of country of birth with presence of CAD. The study included 208,363 non-immigrants and 36,139 immigrants: 13,503 from South Asia, 6,839 from Western Countries, 5,036 from East Asia, 4,374 from the Middle East, 2,481 from Latin America, 2,320 from Caribbean, and 1,586 from Africa. Obstructive CAD was found in 47.1% of immigrants and 47.4% of non-immigrants. Immigrants from South Asia had the highest rate of obstructive CAD at 53.7% and those from the Caribbean had the lowest rate at 32.5%. South Asian men and women had the highest odds of obstructive CAD compared to non-immigrants (Figure). Despite the conventional belief that immigrants have better health status, we found that immigrants in Canada had higher odds of obstructive CAD than non-immigrants. In addition, significant variation exists among patients by country of origin even after accounting for the traditional cardiac risk factors.
Abstract 16704: Impact of Infective versus Sterile Transvenous Lead Removal on Outcomes in Cardiac Implantable Electronic Devices
Authors: Fahimeh Talaei, Qi-Xuan Ang, Mustafa Hassan, Justin Zon-ern Lee, Kamala Tamirisa
Journal: Circulation (2023)

Introduction: Transvenous lead removal (TLR) is associated with increased mortality and morbidity. This study sought to evaluate the impact of TLR on in-hospital mortality and outcomes in patients with and without CIED infection. Methods: Using the nationally representative, all-payer, Nationwide Readmissions Database, we evaluated patients undergoing TLR for CIED infection between January 1, 2017, and December 31, 2020. The indications of TLR were determined on the basis of the presence or absence of bacteremia, septicemia, sepsis, or endocarditis during the initial admission for CIED infection. The impact of infective vs sterile indications of TLR on mortality and major adverse events was studied. Results: Of the 25,144 patients who underwent TLR, 14,037 (55.8%) underwent TLR due to sterile indications and 11,114 (44.1%) underwent TLR due to infective indications with 4,495 patients with (40.5%) systemic and 6,612 (59.53%) with isolated pocket infection. Infective indications of TLR were associated with a significant increase in in-hospital mortality (8.73% vs 0.96%; OR= 5.89; 95% CI 4.81-7.20; &lt;0.001) but not conversion to open heart surgery. Infective indications of TLR were also associated with a significantly increased risk of thromboembolic events of pulmonary emboli and embolic stroke (OR= 3.80; 95% CI 3.23-4.47, &lt;0.001). Conclusions: A higher rate of thromboembolic events associated with infective indications of lead removal may warrant further pursuing this diagnosis in asymptomatic patients.
Abstract 14400: Tipifarnib Mediated Reduction of Circulating Exosomes Inhibit Pressure Overload-Induced Cardiac Remodeling and Hypertrophy
Authors: Vandana Mallaredy, Rajika Roy, Zhongjian Cheng, Charan Thej Gurrala, Darukeshwara Joladarashi, Ajit Magadum, Maria Cimini, May Truongcao, Carolina Gonzalez, Cindy Benedict, Suprit Shadangi, Venkata N Garikipati, jessica Ibetti, Walter J Koch, Raj Kishore
Journal: Circulation (2023)

Circulating extracellular vesicles, including exosomes, and their content have been implicated in cardiac tissue remodeling during cardiovascular disease progression. However, their role in cardiac hypertrophy and heart failure is very limited. Therefore, we investigated the role of circulating exosomes in cardiac dysfunction and remodeling in a transverse aortic constriction (TAC) model of heart failure using a recently identified exosome biogenesis inhibitor, Tipifarnib. Ten-week-old C57BL6J male mice were randomized into three groups i.e., Sham, TAC and Tipifarnib treated (10 mg/kg) TAC (TAC-Tip). The untreated TAC mice showed a significant increase in circulating exosomes along with gradual development of cardiac hypertrophy accompanied with reduced cardiac functions and increased fibrosis. On the contrary, TAC-Tip mice showed a significant reduction in circulating exosomes and remarkably improved cardiac left ventricular functions, reduced cardiac hypertrophy, fibrosis, and systemic inflammation. Strikingly, when primary mouse cardiac fibroblast cells were treated with exosomes derived from serum of TAC mice, the fibrosis related genes expression was significantly amplified compared to those treated with exosomes from TAC-Tip mice serum. Further, systemic injections of TAC-serum exosomes in normal, uninjured mice for 8 weeks, reduced cardiac function and increased cardiomyocyte hypertrophy. Small RNA sequencing analysis of serum exosomes from TAC and TAC-Tip mice displayed an extensively differential exosomal miRNAs profile. To evaluate the crucial role of miRNA in the circulating exosomes, we selected miR 331-5p based on the most differentially expressed miR and validated its expression in heart tissue and serum exosomes of Sham, TAC and TAC-Tip mice. Functional studies showed miR 331-5p inhibited HOXC8, a critical regulator of fibrosis. Overall, our studies reveal a mechanism by which treatment of Tipifarnib in TAC mice, alters not just the exosome numbers but also circulating exosomes content including miR 331-5p that directly inhibits HOXC8 and reduces fibrosis. Thus, Tipifarnib mediated inhibition of circulating exosomes may serve as a viable strategy to prevent progressive cardiac remodeling to heart failure.
Abstract 17308: Patient and Primary Care Provider Experiences From an Implementation Study of a Risk Prediction Tool Integrating a Polygenic Risk Score and the QRISK2 Cardiovascular Risk Calculator
Authors: Professor Ahmet Fuat, Ella Adlen, Mark Monane, Ruth Coll, Elizabeth Little, Jonathan Wild, Farzan Kamali, yusuf soni, Shona Haining, Helen Riding, Carla Giner Delgado, Michael E Weale, Seamus Harrison, Peter Donnelly
Journal: Circulation (2023)

Introduction: We have previously shown that combining a polygenic risk score (PRS) for cardiovascular disease (CVD), with standard clinical risk calculators such as QRISK®2, results in improved CVD risk prediction via an integrated risk tool (CVD-IRT). Research Question: The objective of this study was to explore the implementation of CVD-IRT within routine practice in the UK National Health Service (NHS), through participant and healthcare provider (HCP) surveys and interviews. Methods: The Healthcare Evaluation of Absolute Risk Testing Study (HEART) (NCT05294419), a prospective, single-arm pragmatic trial, enrolled 836 participants undergoing health checks across 12 NHS general practices. QRISK2 and CVD-IRT scores were returned to participants via HCPs. The primary outcome of the study was feasibility of CVD-IRT implementation. This was assessed by a mixed methods approach (quantitative and qualitative methods). Results: After the results were reported and discussed, 520 surveys were completed by participants and 824 surveys were completed by HCPs. Subsequently, 21 participants were interviewed and 13 HCPs attended focus groups or interviews to explore their experiences. 23 HCPs completed a final questionnaire (34.8% physician, 21.7% research nurse, 43.5% other). For 90.7% of reports, HCPs indicated that the CVD-IRT could be incorporated into routine primary care in a straightforward manner. 80% of HCPs agreed that having these tests could lead to better health outcomes for patients, and 68.4% believed that the CVD-IRT could help them manage their patients through a shared decision making process covering lifestyle and treatment options. Participants found the report personally useful (98.5%) and easy to understand (94.3%); agreed that genetic measures are important to identify the risks of developing CVD (85.2%); thought that the test should be widely made available (interview summaries); and would recommend to friends and family (86.8%). Conclusion: The implementation of the CVD-IRT into routine health-checks was recommendable, feasible and well received by both HCPs and participants, who felt that the information was useful, could support clinical decisions, and easy to understand.
Abstract 13421: Meta-Analysis of Penetrance in Genetic Hypertrophic Cardiomyopathy
Authors: Constantin-Cristian Topriceanu, Alexandre C Pereira, James C Moon, Gabriella Captur, Carolyn Y Ho
Journal: Circulation (2023)

Introduction: Hypertrophic cardiomyopathy (HCM) is clasically caused by pathogenic or likely pathogenic (P/LP) variants in genes encoding sarcomeric proteins (G+) leading to left ventricular hypertrophy (LVH). Aim: To contrast cross-sectional penetrance in clinical and population studies, and to determine the phenotypic conversion (% of G+ developing LVH during follow-up) in longitudinal studies ( Figure 1 ). Methods: A systematic literature search was performed. Pooled penetrance (with 95% confidence intervals [CIs]) and phenotypic conversion were calculated with random effects generalized linear mixed model meta-analyses. Calculations were made for each gene and across all genes. Meta-regression was employed to explore sex-related differences. Results: In cross-sectional clinical studies, after excluding probands, penetrance across all genes in relatives carrying P/LP variants identified during cascade screening was 58% (95% CI [53,64]). Penetrance varied from ~32% for myosin light chain 3 to ~65% for myosin heavy chain 7 ( MYH7 ) and troponin T ( TNNT2 ). The mean age of HCM onset was 38 years (95% CI [36, 40]) across all genes, but studies including a higher % of males reported a later age of onset. In contrast, penetrance in population studies was ~10-15%, ranging from 0% in Atherosclerosis Risk in Communities to 18% in the UK Biobank. In longitudinal clinical studies, the pooled phenotypic conversion was 15% (95% CI [8,27]) over an average of ~7 years of follow up, starting from a mean age of ~16 years across all genes. However, it varied from ~12% for myosin binding protein C to ~23% for MYH7 . Conclusions: The penetrance is 5-7-fold higher in a clinical context compared to incidental identification in population studies, suggesting important but currently undefined factors that modify disease expression. More longitudinal studies are needed to improve understanding of penetrance and identify drivers of the transition from genetic susceptibility to overt HCM
Abstract 16562: Subclinical Flow Inefficiencies in Non-Obstructive Hypertrophic Cardiomyopathy Subgroups Revealed by 4D Flow Cardiovascular Magnetic Resonance
Authors: Karin Pola, Zakariye Ashkir, Saul G Myerson, Håkan Arheden, Hugh Watkins, Stefan Neubauer, Per M Arvidsson, Betty Raman
Journal: Circulation (2023)

Background Patients with non-obstructive hypertrophic cardiomyopathy (nHCM) may exhibit flow inefficiencies despite normal flow profiles on transthoracic echocardiogram. We investigated whether left ventricular (LV) kinetic energy (KE) and hemodynamic forces (HDF) on 4D flow CMR are abnormal in nHCM, and examined the impact of genotype and hypertrophy phenotype on flow profiles. Methods 90 participants (70 HCM without echocardiographic outflow tract obstruction and 20 healthy controls) underwent 4D flow CMR. Patients were categorized as phenotype positive (P+) if they had LV hypertrophy (≥15mm or ≥13mm with an HCM family history), or phenotype negative (P-) referring to pre-hypertrophic pathogenic sarcomeric variant carriers. LV KE, HDF and transversal/longitudinal HDF ratio were computed from 4D flow CMR. Results P+ patients and controls were of similar age, but P- were younger. P+, P- and controls had comparable LV ejection fraction on CMR, and LV outflow tract pressure gradients and diastolic velocities on echocardiography (Table 1). Systolic KE was higher in P+ compared to controls (Table 1, Figure 1). Early diastolic KE was higher in P- than P+, reflecting younger P-, but did not differ between P+ and controls. Late diastolic KE was higher in P+ versus P- and controls. Systolic HDF ratio was higher in P+ than controls (Table 1, Figure 1). Diastolic HDF and HDF ratio were similar between P+ and controls. Conclusion Despite comparable flow velocities on echocardiography, nHCM exhibited higher systolic KE and HDF ratio, and late diastolic KE on 4D flow CMR relative to controls. Both the extent and pattern of hypertrophy are important determinants of abnormalities in KE and HDF.
Abstract 17829: Improving Access to Cardiac Rehabilitation for Minorities and Vulnerable Patients With a Multidisciplinary Program in a Large Metropolitan Public Hospital Network
Authors: Mireia Padilla Lopez, Carlos Alviar, Matthew Glenn, Erik LeRoy, Susan Kang, nikki dunham-hoshida, Norma Keller, Alaina Signorastri, Matthew H Vorsanger
Journal: Circulation (2023)

Introduction: Cardiac rehabilitation (CR) improves outcomes after myocardial infarction, cardiac surgery or in chronic heart failure with reduced ejection fraction. However, access to CR is often limited to insured patients or those who can pay out-of-pocket, leaving uninsured or undocumented patients without access to these benefits. Our aim is to describe the implementation and outcomes of a multidisciplinary comprehensive CR program in the largest public health system in the country, as a strategy to mitigate healthcare disparities and improve access to care for minorities. Methods: Our CR program started in March 2021 as a virtual program and opened for in-person care in November 2022. We collected clinical, demographic, socioeconomic, and immigration data as well as data on clinical outcomes such as hospital readmission, mortality, and program completion rates. Results: A total of 202 patients were included (35.6% women, mean age 62), with 83.7% of patients in virtual CR and 16.3 % in in-person CR. The most common ethnic group was Black (41.6%) followed by Hispanic (38.6%). A total of 23.8% were uninsured, 21.3% were undocumented and 52.5% lived below the poverty level reported for New York City. The highest level of education was &lt; 8th grade in 16.8%, high school in 22.8%, at least 2 years of college in 5.5%, &gt; 4 years of college in 7.9% and unknown in 47%. The hospital readmission rate at 6 months was 12.4% and mortality was 1.5%. There were no significant differences in survival or readmission by ethnic group. Of patients completing at least one visit, 72% were active or graduated from virtual CR and 90% were active or graduated for in-person CR (Figure). Conclusions: Our multidisciplinary CR program demonstrates feasibility in providing care to underserved and vulnerable populations, showing excellent results and providing a strategy to decrease healthcare disparities in access to an intervention which improves outcomes across a broad spectrum of cardiac disease.
Abstract 17614: “Watchful Waiting” - Successful Medical Management of an Infected Watchman Device
Authors: Amitoj Sachdeva, Kailash Pant, Yogesh K Agarwal, Amit Mehrotra, Chetan Bhardwaj
Journal: Circulation (2023)

Description of Case: A 68-year-old male with a past medical history of alcoholic cirrhosis, ischemic cardiomyopathy, atrial fibrillation, ventricular tachycardia, and sick sinus syndrome presented with exertional dyspnea and lower extremity edema consistent with acutely decompensated systolic heart failure. He had multiple implantable cardiac devices including a watchman device. He was subsequently found to have methicillin-sensitive staphylococcus aureus (MSSA) bacteremia and developed sepsis. A transesophageal echocardiogram (TEE) was done to evaluate for infective endocarditis and a 1 cm mobile echodensity attached to the anterior aspect of the watchman device was found. Given active bacteremia, the echocardiographic appearance was felt to be most likely consistent with a vegetation. Due to significant medical and cardiac comorbidities, device extraction was deemed very high risk and deferred in favor of antibiotic therapy by a multi-disciplinary team. The patient was treated with intravenous cefazolin and oral rifampin. Clinical defervescence and clearance of bacteremia were achieved. A follow-up TEE in 6 weeks showed complete resolution of the watchman device vegetation. Discussion: Cardiac implantable devices provide significant morbidity and mortality benefits to patients but incur the potential risk of infection. Watchman device infection, though rare, has been reported. The current guidelines recommend the removal of all hardware in patients with established device infection. However, percutaneous, or surgical extraction of the watchman device bears significant risk and may not be feasible in all patients. Our case demonstrates the potential role of antimicrobial therapy alone with close surveillance in treating high-risk patients with watchman device infection.
Abstract 16517: Association of Low Left Atrial Appendage Velocity With Increased Risk of Atrial Fibrillation Recurrence After Catheter Ablation: A Meta-Analysis
Authors: Maharshi Raval, Nishanth Katukuri, Sruthi Venugopalan, Akhil Jain, Vidit Majmundar, Sajid Siddiq, Rupak Desai
Journal: Circulation (2023)

Background: Catheter ablation (CA) is an effective and potentially curative treatment in patients with atrial fibrillation (AF). However, the recurrence of AF following CA treatment in cases of persistent atrial fibrillation (PeAF) remains a significant concern. This study aims to establish a correlation between the peak flow velocity of the left atrial appendage (LAAV) and the AF recurrence post-CA for PeAF. Methods: PubMed/Medline, EMBASE, and SCOPUS databases were systematically reviewed to find studies through June 2023 reporting data on the relationship between the LAAV and the recurrence of AF in individuals who have undergone CA for PeAF. Binary random effects models were used to estimate pooled outcomes. I2 statistics were used to interpret heterogeneity, with I 2 &gt;75% indicating substantial inter-study variation. Leave-one-out meta-analysis was performed to evaluate the effect of each study on the overall estimate. A p&lt;0.05 was considered statistically significant. Results: A total of 9 studies between 2000-2023 were included in our meta-analysis. The pooled univariate analysis revealed no association between LAAV and recurrence of AF in individuals who have undergone CA with a pooled OR of 1.09 (95CI 0.96-1.22) p=0.45, I2=86.59%. The multivariate analysis, after adjusting for overall modifiable risk factors, yielded significant results, with an adjusted odds ratio (aOR) of 1.41 (95CI 1.15-1.74) p&lt;0.01, I2=85.24%. Sensitivity analysis, using the leave-one-out method&amp;nbsp;demonstrated the robustness and stability of the results, indicating that no single study disproportionately influenced the overall&amp;nbsp;findings with aOR 1.41 (95CI 1.15-1.74) p&lt;0.01. Conclusions: This meta-analysis revealed that low LAAV is associated with high-risk of AF recurrence following CA. Identifying a specific subgroup of individuals at high risk of AF recurrence with the help of pre-CA LAA velocity will facilitate the early institution of alternative treatment strategies.