tbuckley/cabot-search huggingface dataset:
Abstract 4141054: Management of Severe Non-Rheumatic Mitral Stenosis in Pregnancy
Authors: Alex Caplan, Favour Nelson, Lucie henry, Henry Lesser, Brendan Carry
Journal: Circulation (2024)

Introduction: Physiologic changes in pregnancy can accentuate valvular pathologies. The modified WHO pregnancy risk classification categorizes severe mitral stenosis (MS) as mWHO Risk Class IV in which pregnancy is contraindicated. Literature on the management of MS in pregnancy is limited to rheumatic heart disease. Those that are non-rheumatic in nature are therefore difficult to characterize. To better understand these differences in management, we present a case of MS from pannus-overgrowth 10 years after bioprosthetic valve placement. Our Case: A 29-year-old primigravid female, with a history of traumatic rupture of the posterior papillary muscle managed by a 25mm Carpentier-Edwards bioprosthetic mitral valve was seen at 13-weeks. A multidisciplinary (MDC) meeting was held with maternal-fetal medicine (MFM) and cardiothoracic surgery. A TEE confirmed severe MS [MVA 1.3cm 2 , mean gradient 19.5 mmHg, and peak velocity of 2.6 m/s] as the result of pannus-overgrowth limiting mobility in 1/3 leaflets. She was not a candidate for balloon valvuloplasty given her bioprosthetic valve, or valve replacement due to the risks cardiopulmonary bypass. She opted to continue pregnancy with medical management. As expected, in the mid-second trimester blood pressure reached its nadir, and her heart rate increased; therefore, metoprolol was started. Exposure to β-blockers is associated with fetal growth restriction (FGR) and the MFM team performed serial growth ultrasounds for close monitoring. At 28-weeks, she developed dyspnea, and the β-blocker dose was titrated. At 32-weeks these symptoms worsened, and furosemide was started. She experienced palpitations, but remote cardiac monitoring was reassuring. The pregnancy was complicated by non-severe FGR and so the MDC decided to pursue a medically indicated planned vaginal delivery in the intensive care unit (ICU) at 35-weeks. Delivery was accomplished via assisted second stage of labor to avoid maternal Valsalva. The postpartum course was uncomplicated. As she desired future childbearing, she underwent successful mechanical valve replacement after 3-months. Discussion: For pregnant patients with MS, heart rate and volume optimization are of critical importance. β-blockers and diuretics are safe and effective in pregnancy and providers should initiate these therapies as needed. We highlight the importance of an MDC approach in patients with MS and confirm that pregnancy and vaginal delivery can be safe.
Abstract 4141050: Calcium to Cross-Bridge Coupling within Intact in vivo Hearts Elucidated by Simultaneous Intracardiac Pressure and Intra-Cardiac Myocytes Calcium Measurements
Authors: Joshua Hale, Laticia Ellankil, Kaycee Nguyen, Lilly McAlister, Katherine Tugwell, Yunwoo Kwon, Carl Tong
Journal: Circulation (2024)

Background: Elucidating key mechanisms of cardiac contraction/relaxation can lead to new treatments for heart failure. Intact papillary muscles produce maximum force at much lower [Ca 2+ ] than de-membraned cardiac tissue and show [Ca 2+ ] to force hysteresis relationship. We then hypothesize that cross-bridge (CB) attachments sustain force generation independent of [Ca 2+ ] after [Ca 2+ ] enabling as a key driver of contraction. Methods: We acquired transgenic mouse model with cardiac myocyte specific endogenous fluorescent calcium sensor GCaMP8. GCaMP8 is green fluorescent protein coupled with calmodulin. We made a novel system using commercial parts and in-house software that can quantify GCaMP8-[Ca 2+ ] fluorescence of in vivo beating heart. We then made simultaneous intra-cardiac pressure and [Ca 2+ ] measurements of in vivo beating hearts. Results: By echocardiography, GCaMP8 hearts demonstrated similar size, reduced left ventricular ejection fraction, slowed maximal myocardial contraction velocity S, similar maximal myocardial relaxation velocity e’, and similar E/e’ ratio in comparison to WT. Thus, GCaMP8 hearts have depressed systolic function but preserved diastolic function. Western blotting did not show any expression differences in SERCA2a or phospholamban. Simultaneous intracardiac pressure and [Ca 2+ ] measurements showed peak [Ca 2+ ] occurring well before peak pressure. Normalizing delay to adjust for different heart rates, peak pressure occurs at 19%±3%SD delay from peak [Ca 2+ ] of heart-beat duration, p&lt;0.0001 n=5. Plot of [Ca 2+ ] vs. pressure showed hysteresis relationship where pressure rises to peak as [Ca 2+ ] falls after initial concordant rise. Pressure rises to only 48%±5%SD of peak at peak [Ca 2+ ], p&lt;0.0001 n=5. Conclusions: We demonstrated CB attachment sustains contraction independent of [Ca 2+ ] within beating in vivo hearts. Unlike systole, calcium chelation has little impact on diastolic function. Modulation of CB function can be a new treatment class.
Abstract 4141302: Endothelial Cell-derived Exosome Regulates the Proliferation and Migration of Smooth Muscle Cells and Aggravate Recurrent In-stent Restenosis
Authors: yu jiang, Fangshun Tan, miao yu, WeiXian Yang, Hai-Yan Qian
Journal: Circulation (2024)

Background: After percutaneous coronary intervention (PCI), 5-10% of patients experience in-stent restenosis (ISR), and among these, 10-20% develop recurrent in-stent restenosis (RISR). Proteins could be encapsulated into exosomes and participate in intercellular signaling, affecting various progression of cardiovascular diseases. However, the effect of exosome-derived proteins on RISR progression needs further exploration. Aims: Vascular endothelial injury initiates restenosis post-PCI, with the excessive proliferation and migration of vascular smooth muscle cells (VSMCs) playing a central role. To elucidate the mechanisms by which exosomes derived from endothelial cells influence the proliferation and migration of VSMCs, thereby contributing to the exacerbation of RISR. Methods: Firstly, coronary plasma was collected from 8 RISR patients and 8 healthy controls. Exosomes were isolated using ultracentrifugation techniques. Protein components in exosomes were sequenced by four-dimensional data-independent acquisition (4D-DIA) quantitative proteomics. Exosomes with high TGF-β1 were co-cultured with primary VSMCs to assess their functional impact on cell behavior. After 24 hours of serum starvation to synchronize cell cycles, the cells were treated with PKH67-labeled exosomes. Subsequent confocal microscopy analysis to evalulate the presence of PKH67-labeled exosomes in VSMCs. Next, we performed cell proliferation assays (CCK-8) and migration assays (wound healing and transwell migration) to evaluate the effects of exosomal transfer on VSMC activity. The expression of TGF-β1, MYH9 and Smad2/3 pathway with their phosphorylation status in exosome-treated VSMCs were tested using WB assays. Results: Exosomes from RISR patients, with high TGF-β1 expression, were originated from endothelial cells and could be internalized by VSMCs. TGF-β1 activated Smad2/3 pathway and then promoted MYH9 expression. In addition, overexpression of TGF-β1 boosted the expression of MYH9, while the knockdown of TGF-β1 has the opposite effect. The functional rescue experiment validated that TGF-β1 can regulate downstream MYH9, and participates in the proliferation and migration of VSMCs via Smad2/3 pathway. Conclusion: Our study suggests that exosome-derived, endothelial cell-originated TGF-β1 is essential to VSMCs proliferation and migration. This process is mediated via TGF-β1- Smad2/3-MYH9 axis.
Abstract 4141210: Renal outcomes in transthyretin cardiac amyloidosis
Authors: Adam Ioannou, Yousuf Razvi, Aldostefano Porcari, Muhammad Rauf, Ana Martinez-Naharro, Lucia Venneri, Philip Hawkins, Julian Gillmore, Marianna Fontana
Journal: Circulation (2024)

Background: Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive cardiomyopathy that commonly presents with concomitant chronic kidney disease. Impaired renal function is associated with worse outcomes, but the prognostic value of changes in renal function over time are yet to be defined. Objectives: This study aimed to assess the prognostic importance of a decline in estimated glomerular filtration rate (eGFR) as a marker of renal progression in a large cohort of patients with ATTR-CA. Methods: A retrospective analysis of 2001 patients diagnosed with ATTR-CA at the National Amyloidosis Centre (NAC) who underwent a baseline and follow-up eGFR assessment at 1-year between 2000-2024. Results: Between baseline and 1-year visits, 208(10.4%) patients experienced renal progression (defined as a decrease in eGFR of &gt;30%). Renal progression was associated with a 2.4-fold higher risk of mortality (HR=2.37,95%CI[1.91-2.94],P&lt;0.001) and the risk was similar across the 3 genotypes (interaction P=0.972) and the 3 NAC disease stages (interaction P=0.172). Deterioration of the cardiorenal axis is tracked through a biomarker progression score composed of NT-proBNP progression (defined as an increase of &gt;700ng/L and &gt;30%) and renal progression. When compared with patients with a stable NT-proBNP and eGFR, a higher risk of mortality was observed in patients experiencing either NT-proBNP or renal progression (HR=2.02,95%CI[1.70-2.40],P&lt;0.001) and those experiencing both NT-proBNP and renal progression (HR=3.77,95%CI[2.84-5.00],P&lt;0.001). Conclusions: Renal progression is frequent and consistently associated with an increased risk of mortality. Combining renal and NT-proBNP progression produces a biomarker progression score that reflects worsening of the cardiorenal axis and identifies patients at the highest risk.
Abstract 4141410: Coronary Calcified Plaque Number and Risk of Incident Cardiovascular Disease in the 75-and-Older Population: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Siyu Zou, Hairong Liu, Yejin Mok, Abhishek Gami, Lin Chen, Matthew Budoff, Michael Blaha, Kunihiro Matsushita
Journal: Circulation (2024)

Background: The Agatston score is established as the clinical measure of coronary artery calcium. However, prognostic implications of the overall number and location of calcified plaques remain unknown in the 75-and-older population. Methods: We analyzed data from 1,746 participants in the ARIC study who underwent non-contrast cardiac-gated chest computed tomography (CT) at visit 7 (2018-19) and were free of cardiovascular disease (CVD) at baseline. In addition to quantifying the Agatston score, we also interpreted the total number of calcified plaques and their location (proximal [before the first major branch] vs. distal [after the first major branch]) in each coronary artery. Multivariable Cox proportional hazards models were used to quantify the association of calcified plaque number with CVD events (adjudicated myocardial infarction, stroke, and heart failure). Participants with zero plaque were treated as a reference, and those with at least one plaque were divided into quartiles of plaque number. Results: During a median follow-up time of 2.8 (interquartile interval 2.4-3.3) years, there were 114 (6.5%) CVD events. After adjusting for traditional CVD risk factors, there was a dose-response relationship between overall calcified plaque number and CVD events (Model 1 in Table), with a hazard ratio of 8.17 (95% CI 2.44, 27.39) in plaque number ≥ 25 (Q4) vs. 0 (no plaques). The association remained statistically significant even after further adjusting for Agatston score (Model 2). When we analyzed proximal and distal plaques separately, the association was more evident in the proximal distribution (e.g., hazard ratio of Q4 vs. no plaques 3.95 (1.42, 11.00) for proximal vs. 1.38 (0.67, 2.85) for distal in Model 2). Conclusion: Calcified coronary plaque number, especially in proximal arteries, was associated with incident CVD events beyond the traditional risk factors and the Agatston score in the 75-and-older population. Our findings suggest the possibility to further optimize the use of cardiac CT beyond the Agatston score for predicting CVD events in this population.
Abstract 4141018: Association of HDL-2b and HDL-3 with severe coronary stenosis in acute myocardial infarction patients: effects of age, gender, and comorbidities
Authors: Bin Wang, DONG LI, Yu Geng, Yujie Wang, Han Cao, Mingkun Tang, Changhua Lv, Tingting Lv, Yajun Xue, Ping Zhang
Journal: Circulation (2024)

Background: It is unclear if the novel, functionally unidentified HDL cholesterol subtypes HDL-2b and HDL-3 can be used to predict acute myocardial infarction (AMI). Methods: This cross-sectional study comprised 1,200 hospitalized patients with AMI identified using ICD-9 coding. The Gensini score was used to assess stenosis severity, defining patients as severe (score ≥50) or mild to moderate (score &lt;50). Differences between groups were determined using one-way analysis of variance or nonparametric testing for continuous variables and chi-square tests for categorical variables. The relationship between HDL-2b, HDL-3, and severe coronary stenosis was investigated using restricted cubic splines (RCS) and logistic regression, with adjustments for age, gender, hypertension, diabetes, stroke, and kidney disease. Each of the covariates listed above was subjected to subgroup analyses. Based on the literature-reported cutoff of 18%, HDL-2b (%) was classified into a new variable, the HDL-2b group (HDL-2b ≥ 18% vs. HDL-2b &lt; 18%). Results: 558 (46.5%) mild to moderate and 642 (53.5%) severe groups differed by HDL-3 (P=0.032) and HDL-2b group (P=0.019), but not by the above covariates or HDL-2b (P=0.324). RCS models revealed strong relationships between severe coronary stenosis and HDL-2b and HDL-3. To predict severe coronary stenosis, the odds ratio (OR) for HDL-3 was 0.98 (95% CI: 0.97-1.00, P=0.010), and for HDL-2b group, the OR was 0.67 (95% CI: 0.50-0.91, P=0.010). HDL-2b, as a continuous variable, had no statistically significant connection with severe coronary stenosis. HDL-3 significantly predicted severe coronary stenosis in subgroups of aged &lt;65 years, females, those with hypertension, without stroke, and without kidney disease (Figure 1). The HDL-2b group was significant in the subgroups aged ≥65 years, males, with hypertension, without stroke, and without kidney disease for the prediction of severe coronary stenosis (Figure 1). Conclusions: HDL-2b (%) values less than 18 and a drop in HDL-3 in AMI patients are associated with significant severe coronary stenosis, with differences identified among subgroups based on age, gender, and comorbidities.
Abstract 4140751: “A silent death: Right heart clot in transit” Acute sub-massive pulmonary embolism
Authors: Kubiat Udoh, RAHUL POTTABATHINI
Journal: Circulation (2024)

An 84-year-old male with a history of prostate cancer not on chemotherapy presented to the ED with complaints of shortness of breath worse on exertion ongoing for 1 week accompanied by generalized malaise. On arrival, his troponins were elevated 373, elevated BNP 934. He was requiring supplemental oxygen and an initial bedside cardiac ultrasound was unremarkable. On day 3 of hospitalization, he experienced a syncopal episode and had acute worsening of hypoxemia that prompted a CT angiography of the chest which revealed bilateral, large clot burden pulmonary emboli with proximal thrombus in both the right and left main pulmonary arteries. He was administered a therapeutic dose of low-molecular weight heparin and transferred to the ICU. Despite his large clot burden, there was absence of obstructive shock. Transthoracic Echocardiogram and bilateral duplex venous ultrasound were obtained to evaluate for right heart strain and clot burden. TTE showed a clot in transit between the right atrium and ventricle, a severely dilated RV with reduced RV systolic function. Extensive clot burden in bilateral lower extremities was visualized on ultrasound. Cardiology was consulted. The risk and benefits of catheter-based aspiration thrombectomy versus thrombolytics (peripheral versus catheter directed) versus surgical thrombectomy versus anticoagulation alone were discussed. Given his high risk of in-hospital mortality, age and frailty, shared-decision making to proceed with anticoagulation alone was decided. Unfortunately, on day 8 of hospitalization, he became bradycardic with no recordable blood pressures, and went into pulseless electrical activity soon after with an eventual demise. In this clinical case, we discussed sub-massive pulmonary embolism (PE) complicated by a right heart clot-in-transit presenting insidiously. Acute sub-massive pulmonary embolism is defined as intermediate risk PE associated with right ventricular dysfunction without hemodynamic instability. Right heart clot in transit is a rare complication of PE and is associated with a high mortality rate of 20-30%. Anticoagulation is the 1st line treatment for sub-massive PE but definite therapy regarding the management of right heart clot in transit is still debated: CATHETER-BASED INTERVENTION versus SURGICAL THROMBECTOMY as none is thought to be superior. Indication for either therapy centers on hemodynamic compromise which is assessed on a case-by-case basis based on the clinician’s judgement.
Abstract 4140651: Effect of Statin Therapy on Cardiovascular Events in High-Risk Group Identified by a Coronary Artery Calcium-Trained Deep Learning Model Using Retinal Imaging: A Propensity Score-Matched Study from the UK Biobank
Authors: Yunnie Cho, Tyler Hyungtaek Rim, Chan Joo Lee, Sung Ha Park, Hyeonmin Kim, Chanyang Seo, Marco Yu, Sahil Thakur, Tien Wong, Ching Yu Cheng
Journal: Circulation (2024)

Introduction: Cardiovascular disease (CVD) remains the leading cause of mortality globally, necessitating improved risk stratification and preventive strategies. Reti-CVD, a deep learning model, predicts CVD risk by analyzing retinal images to detect subtle vascular changes indicative of coronary artery calcium presence. This study evaluates the efficacy of statin therapy in individuals identified as high-risk by Reti-CVD using propensity score matching and survival analysis. Hypothesis: Individuals with high Reti-CVD scores will benefit significantly from statin therapy, resulting in a reduced incidence of cardiovascular events compared to those not receiving statins. Methods: Data from the UK Biobank were utilized to perform 1:1 propensity score matching, comparing statin users and non-users. Matching was based on age, gender, race, BMI, systolic blood pressure, diastolic blood pressure, medication use for blood pressure, diabetes status, smoking status, alcohol consumption, and socioeconomic status. Within a cohort identified as high-risk by a deep learning model, survival analysis of a mean follow-up period of 9.83 years for CVD outcomes was conducted, with the hazard ratio calculated for statin users versus non-users. Results: In the unmatched cohort, significant differences were observed in several variables including age and gender between statin users (n=3,008) and non-users (n=42,373) as shown in Table 1. Post-matching, the cohort comprised 3,008 statin users and 3,008 non-users, with standardized mean differences significantly reduced for most variables. For the high Reti-CVD cohort, the hazard ratio for CVD outcomes in the statin group was 0.76 (95% CI: 0.50-1.14), indicating a 24% reduction in the risk of cardiovascular events compared to non-users. In comparison, the low to medium Reti-CVD cohort had a hazard ratio of 1.22 (95% CI: 0.90-1.68). Discussion: Findings suggest that individuals with high Reti-CVD scores likely benefit from statin therapy, as indicated by a trend towards reduced cardiovascular events. Reti-CVD shows potential in refining risk stratification for guiding statin therapy decisions. The integration of deep learning models like Reti-CVD in clinical practice could provide targeted interventions for high-risk populations.
Abstract 4140673: Prognostic Value of Renal Function Biomarkers in Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis
Authors: Peyvand Parhizkar Roudsari, Amir Hossein Behnoush, Ali Moradi, Salehi Sadaf, Mohammad Keykhaei, Kaveh Hosseini, Edward Gomes, Jasmine Malhi, Christopher Chew, Masih Tajdini
Journal: Circulation (2024)

Background: Considering the high prevalence and comparable five-year mortality rates of heart failure with preserved ejection fraction (HFpEF) to heart failure with reduced ejection fraction (HFrEF), and the inconsistent results regarding prognostic biomarkers for HFpEF, we aim to systematically review studies evaluating the prognostic role of common kidney function markers in HFpEF. Methods: Following PRISMA guidelines, a systematic search was performed in online databases from inception to March 2024. Studies that primarily assessed the association of blood urea nitrogen (BUN), uric acid (UA), creatinine (Cr), estimated glomerular filtration rate (eGFR), and cystatin-C with HFpEF outcomes were included. A random-effects meta-analysis was conducted to pool the hazard ratios (HRs) and their 95% confidence intervals (CIs) for a 1-unit increase in markers or higher levels versus lower levels for the incidence of adverse events, including all-cause mortality, HF readmission, cardiac mortality, and composite outcomes. Results: Out of 2491 reviewed studies, 80 were included. A significant correlation between BUN levels and HFpEF outcomes, mainly HF readmission and all-cause mortality, was found. The meta-analysis showed that a 1-unit increase in BUN was linked to a higher hazard of these events (HR 1.02, 95% CI 1.01 to 1.03, P = 0.0003). A 1-unit increase in UA resulted in a higher incidence of adverse events (HR 1.13, 95% CI 1.05 to 1.21, P = 0.0005). Higher serum Cr levels were linked to increased all-cause mortality, with a 1-unit increase in Cr leading to a higher incidence of adverse events (HR 1.17, 95% CI 1.06 to 1.29, P = 0.0017). Higher eGFR values were associated with lower mortality and hospitalization (HR 0.99, 95% CI 0.98 to 0.99, P &lt; 0.0001). The predictive value of cystatin-C was also demonstrated, with its increased levels correlating with higher mortality and readmission, showing a higher hazard ratio (compared to others) of 1.43 (95% CI 1.21 to 1.75, P &lt; 0.0001). It appears that among continuous variables, cystatin-C works better to predict adverse outcomes in HFpEF (figure). Conclusion: Renal function biomarkers play a significant role in predicting HFpEF outcomes, aiding in better risk assessment and patient management.