tbuckley/cabot-search huggingface dataset:
Abstract 4144168: Five Years Post Heart Transplant Outcomes in Patients with Amyloidosis: A Single Center Experience
Authors: Khush Patel, Zoe Tu, Ashrith Guha, Janardhana GORTHI, Allison Yun, Jill Krisl, Mahwash Kassi, Ju Kim, Rayan Yousefzai, Mark Ghobrial, Osama Gaber, Arvind Bhimaraj
Journal: Circulation (2024)

Introduction: Many patients with amyloidosis can have advanced cardiac involvement, that drives mortality. Due to lack of definitive therapies that can reverse cardiac infiltration, cardiac replacement is the only hope for these patients. Durable left ventricular assist devices are not a good option; hence heart transplant remains mainstay. We present here long-term outcomes from a single center. Methods: Using EPIC Electronic Health Records’ database Clarity and UNOS center-specific report builder, we abstracted clinical information of patients who underwent a heart transplantation for cardiac amyloidosis at our center from 2004 to 2023. Results: Fifty-one patients underwent heart transplant for cardiac amyloidosis: 32 for Amyloid Light chain (AL) and 19 for Amyloidosis Transthyretin (TTR). Majority were males (Table 1). Of the AL transplants, 6 received concomitant kidney, 2 liver and 2 lung transplantation and of the TTR, 1 received concomitant kidney and 16 concomitant liver transplantation. There were more multi-organs in TTR compared to AL cardiac transplants (17 vs 10, p&lt;0.001). The majority (78%) were transplanted at a higher listing status (Status 1A in older system and Status 2 in the newer system) and in the ICU at the time of transplant. Donor, baseline, and post-transplant characteristics are presented in Table 1. Five-year survival for AL cardiac transplantation was 71% compared to 92% in TTR amyloidosis with no significant difference between both (Figure 1). Majority of the causes of death were noncardiac. Conclusion: Select patients with end stage AL and TTR amyloidosis can successfully have prolongation of life with heart transplantation like any other etiology of end stage heart failure. Their 5 year outcomes are similar to other non-amyloid transplant patients reported in national registries.
Abstract 4144119: Association Between High-Intensity Exercise and Progressive Aortopathy in Patients with Bicuspid Aortic Valve
Authors: Meilynn Shi, Danish Saleh, Margaret Simons, Kira Gerweck, Abigail Baldridge, Jane Kruse, Lisa Wilsbacher, chris mehta, S. Christopher Malaisrie, JYOTHY PUTHUMANA
Journal: Circulation (2024)

Background: Individuals with aortic dilation (≥4.0cm) or aneurysm (≥4.5cm) are encouraged to avoid high-intensity sports. However, the incidence of aortic dissection in patients with bicuspid aortic valve (BAV) is low. Restricting physical activity can also impact cardiovascular outcomes. Aims: The impact of exercise on progressive BAV aortopathy is not well understood. This observational study examines the association of exercise intensity with change in aortic dimensions in BAV patients with aortic dilation. Methods: Data was collected from a prospectively enrolled BAV cohort established by the Bluhm Cardiovascular Institute (BCVI) in 2005. BAV patients with aortic diameter ≥4.0cm on CT/MRI and without prior aortic intervention were included. Activity intensity was graded based on AHA/ACC Classification of Sports. Patients who engaged in high dynamic/static component activities for ≥4 hours/week were classified as high-intensity exercisers. Those who engaged in the same activities for &lt;4 hours/week or engaged in low static/dynamic activities or no activity were classified as less than high-intensity exercisers. Results: There were 65 high-intensity exercisers and 44 less than high-intensity exercisers. Median follow-up was 9 years (IQR 5.5-11.2). There were no significant differences in demographics, risk factors, or beta-blocker and statin use (Table 1). No statistically significant differences were observed in annual rate of change of the maximal dimension of the sinus of Valsalva (0.09 vs 0.19mm, p=0.15), sinotubular junction (0.12 vs 0.16mm, p=0.60), mid-ascending aorta (0.25 vs 0.24mm, p=0.88), or proximal ascending aortic arch (0.14 vs 0.21mm, p=0.21) between the two groups (Figure 1). Conclusions: High-intensity exercise was not associated with progressive aortic dilation in patients with BAV. This observation warrants further study of exercise restrictions in patients with BAV and aortic dilation as these may deter otherwise healthful cardiovascular behaviors.
Abstract 4144060: Prevalence, Clinical Characteristics, and Outcomes of Patients with Genotype-Positive Arrhythmogenic Cardiomyopathy Presenting with a Sentinel Sudden Cardiac Arrest
Authors: William Swain, Ramin Garmany, Matteo Castrichini, Johan Bos, Raquel Neves, Michael Ackerman, John Giudicessi
Journal: Circulation (2024)

Background: Arrhythmogenic cardiomyopathy (ACM) is a genetic heart disease characterized by proclivity for ventricular arrhythmias and systolic dysfunction. Rarely, sudden cardiac arrest (SCA) is the presenting event in ACM. These individuals may have concealed disease with no appreciable structural manifestations on imaging. Aims: To determine the prevalence, clinical features, and outcomes of patients with genotype-positive ACM who presented with a sentinel SCA. Methods: In this retrospective study, 445 genotype-positive ACM patients evaluated from 1/2015-4/2024 were analyzed to identify those whose initial presentation was SCA. Pertinent demographic, clinical, genetic, and outcome data were extracted from the electronic medical record. Structural manifestations were defined by having one of the following on baseline TTE: EF &lt; 50%, LVEDV &gt;56 mL (male) or &gt;51 mL (female), or regional RV akinesia, dyskinesia, or aneurysm. Categorical variables are presented as number (%), and continuous variables as median (IQR). Statistical analysis was done using Fisher’s exact test (categorical), t-test (continuous), and Logrank test (survival). Patients were censored at time of transplant, death, or last followup. Results: Overall, 14/445 (3%) ACM patients presented with sentinel SCA [71% male; median age at SCA 39 (IQR 30-46)]. The most common genetic substrates were DSP -encoded desmoplakin (n=4; 29%), LMNA -encoded lamin A/C (n=3; 21%), and PKP2 -encoded plakophilin-2 (n=3; 21%). During a median followup of 8.4 years, 12 (86%) experienced appropriate ICD shocks, 8 (57%) required catheter ablation for ventricular arrhythmias, 6 (42%) underwent transplant, and 2 (14%) died of cardiac causes. Notably, 5 (35%) patients did not have evidence of structural disease during baseline evaluation. Compared to those with structural disease, this group was younger [median age 28 (IQR 21-29) vs 45 (IQR 41-48), p = 0.002] and less likely to undergo transplant [0 (0%) vs 6 (42%), p = 0.03]. Conclusions: Sentinel SCA is a rare presentation in ACM and may precede overt structural cardiac changes in a subset of younger patients. This population remains at increased risk for recurrent ventricular arrhythmias and often require advanced therapies.
Abstract 4144180: Preclinical Investigation of Integration and Tissue Response to a Novel Growth-Accommodating Transcatheter Pulmonary Valve
Authors: Nnaoma Agwu, Tanya Burney, Ekaterina Perminov, Christopher Alcantara, Robert Edwards, michael recto, Arash Kheradvar
Journal: Circulation (2024)

Background: Among 40,000 newborns with congenital heart defects, many face right ventricular outflow tract (RVOT) dysfunction, requiring pulmonary valve replacement. Existing options like the Melody™ transcatheter pulmonary valve aren't suitable for children under 20 kg, posing risks to the right ventricle (RV) as smaller children await weight gain. To avoid the detrimental effects to the RV in young children, we have developed IRIS Valve, a novel growth accommodating transcatheter pulmonary heart valve. This valve can be implanted using a 12-Fr transcatheter delivery system, catering to children weighing as little as 8 kg. As the native valve annulus expands, the IRIS Valve can be balloon-expanded up to 20mm. Hypothesis: We investigate the successful integration of the IRIS Valve into the RVOT six months after implantation. Aims: We aimed to assess the IRIS Valve's integration and chronic response over a six-month period in Yucatan mini-pigs to ensure the prosthetic valve's integrity. Methods: Derived from origami ideas, the IRIS Valve maintains its fully-coapted trileaflet design crafted from porcine pericardial tissue, in a diameter range from 12 mm to 20 mm (Fig. 1). The animal implantation studies involved seven Yucatan pigs weighing between 8 and 17 kg. The implantation was performed using a 12- or 14-Fr delivery catheter. The valves were appropriately balloon-expanded to accommodate the increasing size of the animals. Six months post-implantation, two animals were euthanized, and their hearts were harvested for histopathological analysis. The RVOT and proximal pulmonary artery, containing the IRIS Valve, were excised, stained with H&amp;E, and embedded into MMA blocks. Results: All seven implanted IRIS Valves maintained precise positioning at the native pulmonary valve and exhibited either no or minimal regurgitation across pigs with diverse pulmonary annulus sizes (Fig. 2). Macroscopic examination post-euthanasia revealed intact valve leaflets. Histopathological examination with H&amp;E staining demonstrated robust integration of IRIS Valve into the RVOT wall, accompanied by a variable chronic inflammatory response characterized by mixed lymphocytes and macrophages, as well as multinucleated giant cells reacting to both the ePFTE skirt and suture material (Fig. 3). Conclusions: Our findings indicate that the IRIS transcatheter pulmonary valve maintains its integrity throughout the 6-month study period and exhibits characteristic chronic inflammatory markers.
Abstract 4144054: Circulating Senescence-Associated Secretory Phenotype (SASP) Proteins Are Associated with Risk of Late Life Heart Failure: the ARIC Study
Authors: Arshama Dehghan, Fernando Giugni, Victoria Lamberson, Yimin Yang, Eric Boerwinkle, Myriam Fornage, Chiara Giannarelli, Morgan Grams, B Gwen Windham, Thomas Mosley, Priya Palta, Bing Yu, Amil Shah
Journal: Circulation (2024)

Introduction: Emerging evidence suggests a role for cellular senescence in the pathogenesis of age-related cardiac dysfunction. Senescence-associated secretory phenotype (SASP) is a hallmark of senescent cells, but the extent to which circulating SASP protein levels associate with cardiac dysfunction is not known. Objectives: Determine associations of plasma SASP proteins with subclinical cardiac dysfunction and incident heart failure (HF). Methods: Among 4,484 HF-free participants in the community-based Atherosclerosis Risk in Communities study who attended the 5 th study visit (2011-2013) and underwent protocol echocardiography, we measured 25 core SASP proteins (SomaScan aptamer-affinity assay). We assessed their associations with cardiac structure/function and incident adjudicated HF using multivariable linear and Cox proportional hazards models adjusted for demographics and clinical characteristics. Results: The mean age was 76±5 years, 58% were female, 17% reported Black race, and mean LVEF was 66±6%. 439 incident HF events occurred over 8 [IQR 7-9] year follow-up. Eight of 25 core SASP proteins associated with risk of incident HF at FDR &lt;0.05 (GDF15, IGFBP2, IGFBP7, TIMP2, TIMP1, MMP2, CTSB, CST3; Figure A). Among those, 6 proteins (TIMP1, TIMP2, IGFBP2, MMP2, IGFB7, GDF15) were associated with both incident HFrEF (n=179 events) and HFpEF (n=201 events) at FDR significance, while CST3 was only associated with HFpEF, and CTSB only with HFrEF. These 8 proteins were also generally associated with greater LV size and worse LA reservoir strain but showed differential associations with worse global longitudinal strain (IGFBP2, TIMP2, MMP2, CTSB) versus diastolic measures including E/e, LAVi, and PASP (CST3, IGFBP7; Figure B). Conclusion: Plasma values of a subset of core SASP proteins associate with cardiac dysfunction and HF risk in older adults, supporting cellular senescence-related mechanisms as a contributor to late-life HF risk.
Abstract 4144179: Cardiac Arginination Activates RIP3/CAMKII/MLKL Signaling RALBP1 Signal for ICIs-associated Myocarditis
Authors: Xuejun Wang
Journal: Circulation (2024)

Background: ICIs-induced cardiotoxicity, particularly myocarditis, poses a significant risk. This study aims to elucidate evidence of direct damage to cardiomyocytes by ICIs and explore potential molecular mechanisms for preventing ICIAM. Methods: Non-targeted metabolomics examined differential metabolites changes in ICIAM patients and mice. Mass spectrometry identified substrates and modification sites of the enzyme acting on aminoacyl-tRNA synthetases (ARSs). Specific acylation modification site antibody for RALBP1 were customized. The levels of endogenous and exogenous arginine acylation-modified RALBP1 were validated in cells. Immunofluorescence staining was performed to verify the degree of acylation modification. RALBP1 knockout were generated to investigate the impact of RALBP1 on cardiac function and related signaling pathways. RALBP1 deacylation modification was verified by SIRT3 knock out. RALBP1 inhibitor RBC8 validated the therapeutic effects of arginylation modification on ICIAM mice. Finally, the effect of acylation modification on RALBP1 399th lysine spot mutation (K399R) and demodification (K399A). Results: ICIs could induce necroptosis in cadiomyocytes through MAMs-CAMKIIδ pathways. Non-targeted metabolomics indicated arginine-related metabolism might be significant in mice and human. Meanwhile, ARSs for arginine could bind to downstream substrate RALBP1 and catalyze arginylation, which was significantly increased in ICIAM. RALBP1 knockout significantly improved cardiac function, reduced arginylation reaction, inhibition of MAM-CAMKIIδ pathway activation in ICIAM mice. SIRT3 could bind to RALBP1 to inhibit acylation reaction. Necroptosis was inhibited after arginine deacetylation modification occured. RBC8 could significantly improve mouse cardiac function and suppress necroptosis occurrence. K399A-RALBP1 exhibited a increased cardiac function after deacetylation modification and inhibited necroptosis. Conversely, K399A-RALBP1 exhibited a decreased cardiac function after increased arginylation reaction and activated necroptosis. Conclusion: Increased serum arginine levels increases the risk of developing myocarditis in cancer patients receiving ICIs therapy by promoting RALBP1 signaling. Inhibiting RALBP1 acylation reaction or RARS activity, suppressing MAMs-CaMKIIδ pathway activation, prevents ICIAM occurrence, highlighting the potential role of nutritional and drug interventions as a novel strategy for prevention and treatment of ICIAM.
Abstract 4144153: Artificially Sweetened Beverages and Cardiovascular Events: A Meta-Analysis of Nearly One Million Cohort Patients
Authors: Ivo Queiroz, Maria Luiza Rodrigues Defante, Lucas Barbosa, Beatriz X. Mendes, Vanio do Livramento Junior Antunes, Roberto Mazetto, Elisio Bulhoes, Catarina Silva, Pedro Romeiro, Camila Guida
Journal: Circulation (2024)

Background: With the rising use of artificial sweeteners as sugar substitutes, concerns regarding their impact on cardiovascular health have emerged. Despite approval by national food regulatory agencies, evidence of their association with clinically significant cardiovascular events remains inconclusive. This study aimed to assess this relationship through a systematic review and meta-analysis. Methods: PubMed, Embase, and Cochrane databases were systematically searched for cohort studies investigating the incidence of stroke, cardiovascular death (CVD), coronary heart disease (CHD), and all-cause mortality (ACM) among individuals with high consumption of artificially sweetened beverages (ASBs) compared to minimal or no consumption. Pooled event prevalence and hazard ratios (HR) with 95% confidence intervals (CI) were calculated using a random-effects model in R software, with heterogeneity assessed via I2 statistics. Results: After overlapping population disposal, eight cohorts comprising 917,971 patients (mean age 52 years; 67.7% female) were included. Analyses were conducted on patient groups with data adjusted for dietary factors, comorbidities, and family history of heart disease. High Consumption of ASBs was significantly associated with a higher risk of ACM (HR 1.1760; 95% CI 1.0186-1.3578, p=0,027), stroke (HR 1.2501; 95% CI 1.0555-1.4807, p=0,01) and CVD (HR 1.4722; 95% CI 1.2821-1.6905, p&lt;0,001). There was no statistically significant association found for CHD (HR 1.1215; 95% CI 0.9280-1.3554, p=0,235). Conclusion: In this meta-analysis, we found a significant association between high consumption of ASBs and increased incidence of ACM, CVD, and stroke highlighting potential cardiovascular implications. Further studies with improved methodologies are needed to corroborate these findings and elucidate the underlying mechanisms.
Abstract 4144064: AI-enabled bone mineral density (AutoBMD AI) measurement in coronary artery calcium (CAC) scans associated with high CAC score independently of conventional risk factors: Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Morteza Naghavi, Kyle Atlas, Chenyu Zhang, Anthony Reeves, Thomas Atlas, Claudia Henschke, David Yankelevitz, Sion Roy, Matthew Budoff
Journal: Circulation (2024)

Background: The association between low bone mineral density (BMD) and coronary artery calcium (CAC) has been reported before using manual measurement of thoracic BMD. Such manual measurements are time-consuming and subject to operator errors. We therefore used an AI-enabled BMD measurement tool to explore the relationship between CAC and BMD independent of traditional risk factors. Methods: The validation of AutoBMD AI (HeartLung.AI, Houston TX) has been reported previously. We applied AutoBMD to CAC scans of 6043 individuals (53.3% female, age 61.9±10.2 years) from the baseline examination (2000-2002) of MESA. Thoracic BMD was measured in T7-T9 vertebrae. Osteoporosis was defined as a T-Score below -2.5. Cox proportional hazards regression was used to calculate hazard ratios (HR) per unit change for 10-year coronary heart disease (CHD) prediction. Results: Average BMD in men and women were 164.4 ± 45.1 and 163.1 ± 50.0 g/cm 3 respectively (P=0.3467). Average CAC score for men and women were 223.4 ± 544.0 and 76.2 ± 241.3 cm 3 respectively (P&lt;0.0001). A total of 1672 cases were classified as osteoporotic, which included 986 (58.0%) men and 714 (42.0%) women. After adjusting for age, gender and conventional CVD risk factors, average CAC score in osteoporotic cases versus normal BMD was 170.1 ± 531.1 vs. 130.4 ± 272.8 respectively (P = 0.004). Decreased BMD was associated with CHD independently of CAC score and CVD risk factors (HR=0.997, p=0.0143). Conclusion: Low BMD and high CAC are associated independently of age, gender, and traditional risk factors of cardiovascular diseases. Further studies are warranted to evaluate the potential added value of BMD to CAC for prediction of adverse events.
Abstract 4144181: Sociodemographic and Clinical Correlates of Right Ventricular Structure and Function, and Serial Change among Hispanics/Latinos: The Echocardiographic Study of Latinos (ECHO-SOL)
Authors: Juan Cedeno, Priscilla Duran Luciano, Cristian Zamora, Yawen Yuan, Ayana April-Sanders, Mayank Kansal, Barry Hurwitz, Gregory Talavera, Robert Kaplan, Sanjiv Shah, Martha Daviglus, Franklyn Gonzalez, Carlos Rodriguez
Journal: Circulation (2024)

Introduction: The role of the right ventricle (RV) in influencing clinical outcomes and overall survival is well established. However,RV serial change over time and the influence of sociodemographic and clinical factors on RV structure/function remains understudied, especially among Hispanics/Latinos. Methods: ECHO-SOL comprehensively assessed RV structure and function in Hispanic/Latino 1643 adults at baseline (visit 1 2011-2014) and 4.3 years later (visit 2 2015-2019). RV functional parameters included were RV peak S’ velocity (PsV), fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE); structural parameters : RV systolic (RVSA) and diastolic (RVDA) area; and hemodynamic parameters: maximal tricuspid pressure gradient (TR max PG), velocity time integral (VTI). Regression models were employed to assess the association of sociodemographic factors with RV structure/function at baseline. Marginal models were used to estimate RV change between visits. All analyses were weighted to account for complex survey design. Results: At baseline, 41.5% were female, mean age 56.38±0.39 years. Increasing age was associated with worse RV systolic function, evidenced by functional parameters (lower TAPSE, S’ velocity) but lower RVDA. Females had worse RV structure/function (greater RVDA and decreased FAC) but better RV longitudinal shortening (greater TAPSE, PsV). Higher BMI was related to worse RV functional (decreased FAC) and structural parameters (greater RVDA). Higher income (&gt;75K) correlated with better RV longitudinal shortening (PsV). First generation immigrants had worse RV structure with higher RVDA. ( Table 1a) RV structure and function worsened over time ( Table 1b ), as evidenced by an change in all parameters: increased RV size (greater RVSA, RVDA), impaired systolic function (lower FAC) and longitudinal shortening (lower TAPSE,PsV), along with impaired stroke volume (lower TR max PG,VTI). Conclusion: Among Hispanic/Latinos, different sociodemographic and clinical factors were associated with RV morphology and function. Overall, RV structure and function worsened over time, suggesting that sociodemographic factors may play an important role in the decline of RV parameters in this population.
Abstract 4144217: Ruling-out Left Main Stem Stenosis By Clinical And Stress-ECG Variables: The MASTER Case-Control Multicenter Study
Authors: Marco De Carlo, Marco Fornili, Laura Baglietto, Sergio Berti, Luca Carmisciano, Alberto De Caterina, Simona Fabozzo, Gaetano Antonio Lanza, Nastasia Mancini, Cristiano Massacesi, Danilo Neglia, Maria Concetta Pastore, Giuseppe Patti, Saverio Tremamunno, Giampiero Vizzari, William Weintraub, Pierluigi Temporelli, Raffaele De Caterina
Journal: Circulation (2024)

Background: The ISCHEMIA trial questioned revascularization in chronic coronary syndrome (CCS) patients, but excluding subjects with left main (LM) coronary artery disease (CAD). A widely available diagnostic method excluding LMCAD would expand the implementation of an initial noninvasive strategy. Objective: Assessing the ability of excluding LMCAD through clinical and ECG stress testing (EST) variables in patients undergoing coronary angiography (CAG) for CCS. Methods: In a multicenter retrospective case-control study we evaluated CCS subjects undergoing CAG after a maximal EST. Cases were patients with angiographic ≥50% LM stenosis or ≥70% stenoses of both proximal left anterior descending and proximal circumflex arteries; we matched them with similar patients without LMCAD ( Controls) in a 1:3 ratio. Models were internally validated through logistic regressions. Results: 219 Cases were matched with 554 Controls . The c-statistic was 0.80 (optimism-adjusted: 0.73). Assuming LMCAD prevalence of 5% and a misclassification cost ratio of 1:100 (ratio of the cost of performing CAG in a subject without LMCAD to the cost of not performing CAG in a patient with LMCAD), the negative predictive value was 98.6%, correctly classifying 84.5% of Cases . CAG could be spared in 57.0% of subjects, missing one LMCAD diagnosis every 70 CAGs spared in patients without LMCAD ( Figure ). Conclusions: Among patients with CCS, LMCAD can be predicted with acceptable diagnostic accuracy and a very high negative predictive value through a model based on clinical and EST parameters, allowing an initial noninvasive management of most patients able to perform an EST, reducing the costs of routine coronary imaging. Such results should enlarge the applicability of the ISCHEMIA results when coronary computed tomography angiography, used in ISCHEMIA, is not available, limiting the referral to invasive CAG.