tbuckley/cabot-search huggingface dataset:
Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis
Authors: Carlo Fino, Michele D'Alonzo, attilio iacovoni, Agnese Maccarana, Julien Magne, Philippe Pibarot, Maurizio Merlo, amedeo terzi, MICHELE SENNI, Samuele Bichi, Caterina Simon, DIEGO BELLAVIA
Journal: Circulation (2024)

Background: Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation. Research question: in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial Aim: to test whether MVR provides superior clinical and functional outcomes compared with RMA. Methods: a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge. The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure. Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point Results: Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95). At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p &gt; 0.01) ( Figure 1 ). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p&lt;0.01) ( Figure 2 ). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p&lt;0.01) ( Figure 3 ). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023). Conclusions: In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term
Abstract 4138497: Incidence and predictors of recurrent pericarditis in systemic lupus erythematosus
Authors: Yoo Jin Kim, Jana Lovell, Alaa Diab, Laurence Magder, Daniel Goldman, Michelle Petri, Andrea Fava, Luigi Adamo
Journal: Circulation (2024)

BACKGROUND/PURPOSE: Pericarditis is the most common cardiac manifestation of systemic lupus erythematosus (SLE). In the general population, pericarditis commonly recurs (~30%), likely due to immune-mediated mechanisms. Given the broad immune dysregulation that drives the pathogenesis of SLE, we sought to identify the frequency and risk factors for the recurrence of pericarditis in this unique population. METHODS: Retrospective cohort study of SLE patients enrolled between 1988 and 2023 at a tertiary medical center. The SELENA revision of the SLE Disease Activity Index was used to define pericarditis, and all follow-up clinical encounters were examined after the first reported episode. Recurrent pericarditis was defined as that occurring at least 6 weeks after the first recorded episode of pericarditis. Statistical significance was defined as a p-value of &lt;0.05, and a pooled logistic regression was used to estimate odds ratios for risk factors. Results: Of 2931 patients in the cohort, 590 patients had a history of pericarditis. During a median follow-up of 7 years (IQR: 3 – 14), 20% (n=120) of patients experienced recurrent pericarditis (Table 1). The majority (51%) experienced only one recurrence, whereas 49% of patients had ≥2 recurrences. Several demographic, clinical, serologic, and treatment characteristics were associated with recurrence in the univariate analysis (Table 2). We performed a multivariate analysis using variables of statistical significance (P &lt;0.05) and found that independent predictors of recurrence included younger age (≥60 years vs. &lt;40, RR 0.11 (0.04, 0.32), P &lt;.001), treatment with prednisone ( ≥20 vs. 0 mg, RR 1.99 (1.17, 3.40), P = 0.012), active SLE disease (SLEDAI ≥3 vs. 0, RR 1.55 (1.21, 2.00), P &lt;.001), and time from initial episode (3-10 years vs. &lt;1, RR 0.32 (0.20, 0.52), P &lt;.001) (Figure 1). CONCLUSION: Recurrence of pericarditis in SLE is common (20%) and more likely to occur within one year of onset. Younger patients and those with higher lupus activity are at greater risk of recurrence. As in the general population, oral prednisone is independently associated with a higher chance of recurrence in SLE patients, with a dose-dependent effect. These findings set the basis for future studies to define optimal treatment for recurrent pericarditis in SLE patients and indicate that oral corticosteroids should be avoided when treating pericarditis.
Abstract 4138455: Employing Bioinformatic Tools to Identify High-Risk Variants of Unknown Significance in Aortopathy Genes Associated with Aortic Dissection
Authors: John Depaolo, Dongchuan Guo, David Murdock, Alana Cecchi, Scott LeMaire, Ying Shen, Anthony Estrera, Joseph Coselli, Joshua D. Smith, Michael Bamshad, Scott Damrauer, Dianna Milewicz
Journal: Circulation (2024)

Introduction: Pathogenic (P) or likely pathogenic (LP) aortopathy gene variants cause hereditary thoracic aortic aneurysm and dissection, but P/LP variants only explain approximately 20% of cases of thoracic aortic disease. Variants of unknown significance (VUS) are frequently identified among individuals undergoing genetic testing for thoracic aortic disease, however managing patients with VUSs remains clinically challenging. Hypothesis: Bioinformatic tools can be used to determine thresholds above which VUSs may be considered “high-risk.” Methods: Primary analyses were performed in the Penn Medicine Biobank (PMBB) which is composed of 43,731 participants who volunteered to have clinical information linked to biospecimen data including DNA which has undergone whole exome sequencing. PMBB participants were screened for VUSs in one of 11 aortopathy genes. VUS REVEL, AlphaMissense and minor allele frequency (MAF) high-risk thresholds were derived using cutpointR, a statistical package to optimize continuous variable thresholds based on binary outcomes. These thresholds were applied to VUS carriers in the PMBB and two independent validation cohorts. Logistic regression analysis was performed to test the association of high-risk VUSs with prevalent thoracic aortic disease. Results: There were 11,925 individuals in PMBB who carried at least one missense VUS. Carrying a VUS was associated with a modest increased risk of thoracic aortic aneurysm (TAA: OR=1.14, 95% confidence interval [CI] 1.01 to 1.29, P =0.034) but no increased risk of thoracic aortic dissection (OR=1.04, 95%CI 0.55 to 2.00, P =0.896). As VUS REVEL or AlphaMissense increased, or MAF decreased, the association between VUSs and thoracic aortic disease became statistically significant. Using cutpointR, we derived REVEL (&gt;0.649), AlphaMissense (&gt;0.2543), and MAF (&lt;8.16x10 -6 ) thresholds that together identified 435 high-risk VUSs robustly associated with prevalent dissection (OR=7.85, 95%CI 4.73 to 13.03, P &lt;0.001), though the association with TAA was attenuated (OR=2.35, 95%CI 1.62 to 3.42, P &lt;0.001). Similar results were observed in the UK Biobank (UKB) and Early Onset Sporadic Thoracic Aortic Dissection (ESTAD) cohorts. Conclusions: VUSs that met high-risk bioinformatic thresholds were strongly associated with prevalent aortic dissection in the PMBB, UKB and ESTAD. Future investigation is warranted to determine if these thresholds can instruct clinical care of individuals carrying aortopathy gene VUSs.
Abstract 4138348: Mechanical stress-mediated nuclear envelope damage promotes Aortic Valve Calcification through the ZBP1-RIPK3-NF-κB signaling axis
Authors: Xiaolin Duan, Shuwen Su, Wenyan Li, Xiangjie Lin, minhui Xu, Sijie Jiang, Liusheng Wang, Dingli Xu, Zeng Qingchun
Journal: Circulation (2024)

Methods and Results: We describe a comprehensive characterization of the AVICs nucleus landscape as determined by transmission electron microscopy (TEM) of samples obtained from CAVD patients. Turbulence led to nuclear envelope integrity lose in AVICs cultured in shear stress experiments, with three different fluid conditions [static (ST), laminar stress (LS), and oscillatory stress (OS)], indicated by Western blot and immunofluorescence (IF). Silencing lamin A/C (LMNA) through small interfering RNA (siRNA), accelerated nuclear envelope damage , as indicated by Western blot, qPCR, and immunofluorescence (IF). The formation of Z-DNA and its co-localization with Z-DNA binding protein (ZBP1) was observed due to the nuclear envelope damage by IF. Western blot, qPCR, IHC and IF confirmed Z-DNA-induced inflammation in AVICs through the ZBP1-RIPK3-NF-κB signaling pathway. ZBP1 and RIPK3 knockdown with siRNA markedly reduced the protein level of osteogenic markers alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), and bone morphogenetic protein 2 (BMP2) in VICs. In vivo, aortic valve disease was constructed by direct wire injury (DWI), and we showed that overexpression of LMNA by adeno-associated virus significantly decelerated the progression of aortic valve lesion induced by DWI in mice. Conclusion: Excessive mechanical stress can induce damage to the nuclear envelope of AVICs by causing cytoskeletal remodeling, initiating the formation of Z-DNA, and hastening the calcification process in AVICs and CAVD.
Abstract 4138388: Lipoprotein(a): Real-world Impact of Assay Change
Authors: Janeni Jeevanathan, Sigrid Blom, Thomas Olsen, Kirsten Holven, Erik Arnesen, Torleif Trydal, Borge Nordestgaard, Michael Sovershaev, Ying Chen, Kjetil Retterstol, Jacob Christensen
Journal: Circulation (2024)

Background and aims: Different assays have been used to analyze lipoprotein(a) over time, and the need for standardization of Lp(a) assays is well-known. Nonetheless, the impact of the use of different assays for clinical decision making and risk stratification of individuals is understudied. We aimed to investigate how transitioning between Lp(a) assays at a large central laboratory affected the proportion of individuals with Lp(a) result above clinical thresholds. Methods: We studied nationwide clinical laboratory data from Norway including 185,493 individuals between 18-50 years of age with 272,463 Lp(a) measurements between 2000-2019. Lp(a) was analyzed in non-frozen serum samples using immunoturbidimetric methods from Roche Tina-quant assay (generation 1) in 2000–2009 (N individuals = 75,221) and Siemens LPA assay (N individuals = 123,824) in 2009-2019 in mg/dL units. Because some lipid-lowering drugs can modestly alter plasma Lp(a), the data material was restricted to individuals &lt;50 years due to a low use of medication in this age group. Results: The Roche assay detected 35% more individuals with Lp(a) &gt; 50 mg/dL than the Siemens assay in the total population. In individuals that had measurements analyzed by both Roche and Siemens assays (N = 13,494), the Roche assay detected 40% more individuals with Lp(a) &gt; 50 mg/dL than the Siemens assay (25%, N = 3,373 vs. 18%, N = 2,475), and 70% more individuals with Lp(a) &gt;85 mg/dL than the Siemens assay (11%, N = 1,478 vs. 6.5%, N = 881). Conclusion: The choice of Lp(a) immunoassay can influence interpretation of Lp(a) results and decisions, particularly in individuals approaching clinically relevant Lp(a) thresholds.
Abstract 4138353: Disparities in coronary artery disease-related mortality among patients with obesity in the United States from 1999-2020
Authors: Mushood Ahmed, Hira Javaid, Zain Nadeem, Abdullah Nofal, Aimen Shafiq, Adeel Ahmad, Asad Rahman, Farhan Shahid, Raheel Ahmed, mahboob alam
Journal: Circulation (2024)

Introduction: Coronary artery disease (CAD) is the third leading cause of death in the US for adults aged &gt;35 years. Almost half of the adult US population has obesity, which predisposes to atherosclerosis and may lead to poor prognosis in CAD. We aim to identify CAD-related mortality trends in patients with obesity in the US stratified by age, sex, race, and geographical location. Methods: The CDC-WONDER database was used to extract death certificate data for adults aged ≥25 years. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMRs) per 100,000 persons were calculated, and temporal trends were delineated by calculating annual percent change (APC) and the average APC (AAPC) in the rates using JoinPoint regression analysis. Results: From 1999 to 2020, a total of 182,436 CAD-related deaths occurred in individuals with obesity. The AAMR increased consistently from 1999 to 2018 (APC: 4.48) and surged thereafter till 2020 (APC: 13.91). The AAMR for males (4.91) was almost double that of females (2.76). Non-Hispanic (NH) American Indians or Alaska Natives displayed the highest AAMR (5.37) while NH Asians or Pacific Islanders displayed the lowest (0.88). NH Blacks or African Americans displayed an AAMR of 5.06, followed by NH Whites (3.88) and Hispanics or Latinos (2.6). AAMRs also varied substantially by region (Midwest: 4.09; West: 4; Northeast: 3.67; South: 3.53). States with the highest AAMRs were Vermont and Oklahoma. Non-metropolitan regions exhibited a higher AAMR (4.42) than metropolitan regions (3.64). The adults aged 65-74 years exhibited the greatest CMR (8.99). Conclusion: We observed increasing trends in CAD-related deaths in adults with obesity throughout the study period. The highest mortality was exhibited by males and NH American Indians or Alaska Natives, residents of the Midwest and non-metropolitan areas, and individuals aged 65-74 years. Better healthcare practices and lifestyle modifications should be promoted in these high-risk populations to reduce the CAD-related mortality rates in adults with obesity.
Abstract 4138482: The burden of ischemic heart disease, hypertension, diabetes mellitus, and obesity among older Latino and Chinese adults with and without limited English proficiency
Authors: Edward Shin, Nancy Gordon, Veronica Njuguna, Anika Naidu, Jamal Rana, Joan Lo
Journal: Circulation (2024)

Background: An estimated 15% of Latinos and 34% of Chinese in the US have limited English proficiency (LEP). However, there is limited information on whether ischemic heart disease (IHD) and its risk factors (hypertension, HTN; diabetes mellitus, DM; and obesity) vary by LEP vs. non-LEP status in these ethnic groups. This information may be valuable for targeting healthcare interventions. METHODS: This cross-sectional study used data for Latino (79,588 men, 85,560 women), and Chinese (25,944 men, 32,586 women) adults aged 50-79 years who were members of a northern California health plan in 2018-2019. Age, sex, language preference, obesity (BMI ≥30 for Latino and ≥27.5 kg/m2 for Chinese), and IHD, HTN, and DM diagnoses were abstracted from electronic health records. LEP was defined as Spanish/Chinese vs. English (non-LEP) language preference. Prevalence was compared by LEP status within age-sex groups. Modified Poisson regression was used to estimate age-adjusted prevalence ratios. RESULTS: Among Latino men aged 50-64 (57,835, 39% LEP) and 65-79 (21,753, 30% LEP) and Chinese men aged 50-64 (14,751, 42% LEP) and 65-79 (11,193, 40.3% LEP) years, IHD prevalence was lower in LEP vs. non-LEP (Latino: 3.5% vs. 6.0% and 13.8% vs. 19.0%; Chinese: 3.6% vs. 5.8% and 11.9% vs. 14.5%). Similar trends were observed in women, but IHD prevalence was much lower. Among Latino and Chinese men, HTN and obesity prevalence was lower, but DM was similar. For women, HTN was similar, but DM was higher in LEP Latina (age 50-79) and Chinese adults (age 65-79), while obesity was lower in LEP Chinese but not Latina adults. Differences remained after adjusting for age (aPR). CONCLUSION: The burden of IHD, HTN, and obesity is similar or lower among LEP vs. non-LEP Latino and Chinese adults, while the burden of DM is higher for LEP vs. non-LEP Latina and Chinese women. These findings suggest that while DM prevalence is already high, acculturation is associated with higher risk of developing some chronic CVD conditions, underscoring the need for targeted healthcare interventions. Further research is needed to explore mechanisms driving these disparities and to develop culturally appropriate strategies to improve health outcomes.
Abstract 4138339: Abatacept prevents anti-PD-1-induced inflammatory heart failure development after myocardial ischemic injury in mice
Authors: Tamás Gergely, Zsofia Drobni, Tamas Kovacs, Nabil Sayour, Viktoria Eva Toth, Zsofia Onodi, Marton Kocsis, Nora Fekete, Eva Pallinger, Edit Buzas, Tomas Neilan, Peter Ferdinandy, Zoltan Varga
Journal: Circulation (2024)

Introduction: Immune checkpoint inhibitors (ICI), such as anti-PD-1 monoclonal antibodies are increasingly used in anti-cancer therapy. However, several cardiovascular adverse effects can occur with the use of ICIs, including new-onset heart failure. Hypothesis: We hypothesized that prior myocardial ischemic injury could exacerbate cardiac dysfunction and inflammation caused by anti-PD-1 treatment. Moreover, we investigated whether abatacept, a T-cell co-stimulation blocker, can prevent ICI-induced cardiac effects. Methods: To induce reversible cardiac ischemia, C57Bl/6J mice were treated with isoprenaline (ISOP group) or with PBS (CON group), followed by 16 weeks of recovery period. Following this, mice from both groups were divided into three further treatment groups: isotype control, anti-PD-1, or anti-PD-1 combined with abatacept, and were treated for two weeks, with three weekly intraperitoneal injections. Echocardiography was performed to evaluate cardiac function while myocardial inflammation was assessed by qRT-PCR and immunohistochemistry. Flow cytometry and Western blot were used to investigate changes occurring in the thymus. Results: Mice with normal heart function but with prior ischemic injury and anti-PD-1 treatment (ISOP + anti-PD-1) showed significantly decreased fractional shortening and cardiac index on echocardiography, while in animals with abatacept co-treatment (ISOP+anti-PD-1+abatacept) cardiac function was not altered. Increased immune cell infiltration was seen in the myocardium of the ISOP+anti-PD-1 treated group compared to CON animals, including T-cells and macrophages, with increased expression of pro-inflammatory cytokines, while co-treatment with abatacept ameliorated the inflammatory response. In the thymus, increased expression of PD-1 was found after abatacept co-treatment. Conclusion: Prior myocardial ischemic injury was associated with cardiac dysfunction and inflammation after anti-PD-1 treatment, which was ameliorated by abatacept co-treatment. Patients with prior cardiac ischemic events may be at greater risk for developing ICI-induced cardiotoxicity, including new-onset HF.
Abstract 4138417: A Novel Echocardiography Risk Score Predicted Mortality In Patients With Heart Failure With Preserved Ejection Fraction.
Authors: Katsuomi Iwakura, Nobuaki Tanaka, Masato Okada, ATSUNORI OKAMURA, Watanabe Heitaro, Masahiro Seo, Takaharu Hayashi, Masamichi Yano, Takahisa Yamada, Yasumura Yoshio, Shungo Hikoso, Katsuki Okada, Daisaku Nakatani, Yohei Sotomi, Yasushi Sakata
Journal: Circulation (2024)

Introduction: Patients with heart failure with preserved ejection fraction (HFpEF) exhibit several echocardiographic abnormalities, including diastolic dysfunction, left ventricular (LV) hypertrophy, left atrial enlargement or pulmonary hypertrophy. It is not fully understood how these abnormalities are related with prognosis in HFpEF patients. Hypothesis: A combination of echocardiography parameters can predict clinical outcome in patients with HFpEF. Aims: This study aimed to develop a model to predict all-cause mortality in patients with HFpEF using echocardiography parameters. Methods: We analyzed data from 952 patients (81±9 years, 43% male) registered in the PURSUIT-HFpEF (Prospective, Multicenter, Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study, a multicenter registry of patients hospitalized for acute decompensated HFpEF. Comprehensive echocardiography was performed before discharge. Patients were randomly assigned to the derivation and validation cohorts (2:1 ratio). Stepwise model selection was performed on age, sex and 26 echocardiography parameters to identify independent predictors of mortality. These predictors were used to construct a risk model for mortality. The accuracy of the risk score was validated using time-dependent ROC curves in both the derivation cohort (n=629) and in the validation cohort (n=323). Results: During the follow-up period (720 days, IQR: 376, 1100 days), all-cause death was observed in 248 patients (26.1%). Age, sex, diastolic (DWS), E/e’ ratio, LV mass index, LV posterior wall thickness (PWth), relative wall thickness (RWT), tricuspid regurgitant pressure gradient (TRPG) were selected as independent predictors of all-cause death. The score shown in the Table was applied to each factor, and the sum of the scores was calculated as the risk score. The AUC of the risk score for predicting 1-year mortality in the derivation cohort was 0.71 and the optimal cut-off value of 4.5 provided a sensitivity and specificity of 62.8% and 69.1%, respectively. The AUC for 1-year mortality in the validation cohort was 0.67. Conclusions: The novel echocardiography score effectively predicted mortality in HFpEF. This model could be a valuable tool for risk stratification.