tbuckley/cabot-search huggingface dataset:
Abstract 4142245: Eosinophilic Myocarditis and Duodenitis: A Unique Manifestation of Hypereosinophilic Syndrome
Authors: Alexander Sweeting, Michael Atalay, Saurabh Agarwal, Edward Hulten, Yash Patel
Journal: Circulation (2024)

Description of Case: This case presents a 23-year-old man with history of sickle cell disease and allogeneic peripheral blood stem cell transplantation (SCT) who presented with symptoms of acute substernal chest pain, shortness of breath, abdominal pain, and vomiting. Methods: Performed a comprehensive retrospective analysis of one patient's medical history, clinical presentation, diagnostic assessment, therapeutic intervention, and clinical outcome. Results: Physical exam was remarkable for euvolemia. Electrocardiogram demonstrated sinus rhythm. Laboratory studies revealed a complete blood count significant for eosinophilia of 14,800. Troponins and BNP were elevated at 31 ng/mL and 98 pg/ml respectively. Echocardiogram showed normal biventricular systolic function. CT abdomen/pelvis with contrast showed findings suggestive of esophagitis and duodenal thickening. Biopsy of the duodenum revealed an increased number of eosinophils with scattered lymphocytes and plasma cells. Infectious work-up including stool ova and parasite, tryptase, vitamin B12, uric acid, and IgE were unremarkable. BCR-ABL, CHIC-2 deletion, and peripheral flow cytometry were negative. C-reactive protein was elevated. Cardiac MRI (CMR) findings demonstrated late gadolinium enhancement (LGE) of the mid-inferior segment of the left ventricle with moderate hypokinesis. Patient was treated with a short course of steroids. Repeat CMR 10 weeks later showed resolving LGE in the mid-inferior segment of the left ventricle. Discussion: CMR and duodenal biopsy demonstrated findings consistent with rare manifestation of HES with muti-organ inflammation as evident by left ventricular LGE, duodenal biopsy, and peripheral eosinophilia. Initial management involves prompt initiation of immunosuppressive therapy to mitigate eosinophilic infiltration and end-organ damage. Diagnostic modalities such as tissue biopsy, advanced imaging, and laboratory testing play crucial roles in confirming the diagnosis. Follow-up CMR can help follow the response treatment and rule-out confounding disease processes, as seen in our case. In conclusion, HES is a rare disorder with variable presentations. Eosinophilic myocarditis, a life-threatening sequala of HES, should be considered as a differential in patients that develop heart failure symptoms and eosinophilia after SCT.
Abstract 4142314: ECG predictors for readmission in patients with heart failure: A meta-analysis
Authors: Reha Kumar, Shijie Zhou, Douglas Lee, Andrew Ha
Journal: Circulation (2024)

Background: Reducing heart failure (HF) readmission rates remains a global healthcare priority. Current strategies for preventing HF hospitalizations are limited by a lack of accurate predictive models to stratify readmission risk. Electrocardiograms (ECG) provide pertinent information and are broadly available as part of routine cardiac care. We conducted a meta-analysis to identify ECG predictors of readmission in patients with HF. Methods: PubMed, Embase, Cochrane Central and CINAHL were searched, from inception to December 2023. The search strategy was comprised of indexed terms and keywords related to HF, readmission , and electrocardiography. Two reviewers screened relevant studies and extracted data around study design, patient demographics and outcomes. Statistical analysis : Odds Ratio (OR) data and 95% confidence intervals (CI) were calculated on a logarithmic scale using inverse variance method. Pooled OR and 95% CIs were computed using a random-effects model. Results: Of the 409 articles screened, 21 were included for final review. 32,337 patients were analyzed across 8 retrospective studies, 10 prospective cohort studies, 2 registry trials and 1 post-hoc analysis of a randomized control trial. Outcome data were collected for 28 individual ECG variables, which were classified into 5 categories: conduction delay - defined as QRS &gt;120ms (n=7), atrial fibrillation/flutter (n=6), sinus rhythm (n=3), heart rate (n=3), QT C interval (n=3) and QRS-T angle (n=2). Four remaining variables did not fit into these categories (1D). On pooled analysis, presence of atrial fibrillation/flutter [OR 1.54, 95% CI 1.22-1.95, p &lt;0.01] and conduction delay [OR 1.13, 95% CI 1.05-1.22, p &lt;0.01] were associated with higher readmission risk (1A, 1B). Presence of sinus rhythm was associated with lower readmission risk [OR 0.62, 95% CI 0.53-0.72, p &lt;0.01] (1C). Pooled data for heart rate, QRS-T angle and QT C interval were not statistically significant. Conclusion: Presence of atrial fibrillation/flutter and conduction delay on ECG are associated with increased risk while sinus rhythm is associated with lower risk of HF readmission. These findings should be explored further to identify those with HF at risk of readmission.
Abstract 4142287: 4-Phenylbutyric Acid Reduces Endoplasmic Reticulum Retention and Partially Restores Function of LDLR p.D622N Mutation In Vitro: A Potential Therapy for Hypercholesterolemia
Authors: Yongxiang Wang, piyi zhang, ming bai, Zheng Zhang
Journal: Circulation (2024)

Background: We identified a family with familial hypercholesterolemia (FH). The proband presented with corneal arcus, skin, and tendon xanthomas, significant stenosis in the coronary circumflex and right coronary arteries, and severely elevated plasma LDL levels. Treatment with statins, ezetimibe, PCSK9 monoclonal antibodies (Alirocumab and Evolocumab), and inclisiran, which target LDLR function, resulted in minimal LDL reduction.In China, evinacumab is not available, so the patient has to rely on long-term lipid apheresis (plasma exchange). Methods: Genetic testing revealed the proband harbored three mutations in the LDLR gene: c.1864G&gt;A (p.D622N), c.1448G&gt;A (p.W483*), and c.292G&gt;A (p.G98S). D622N and G98S were on the same allele, while W483* was on the other allele. Mutant plasmids were constructed and transfected into HEK293T cells. Western blot and immunofluorescence co-localization assays were used to assess LDLR protein expression and localization. The LDLR function was evaluated using Dil-LDL uptake assays. Additionally, cells were treated with 4 mM 4-phenylbutyric acid for 48 hours to examine its impact on LDLR function. Results: The Western Blot test showed that the W483* mutation broke down the LDLR protein almost completely. The D622N mutation, on the other hand, only showed the precursor form and not the mature form. Finally, the G98S mutation showed that LDLR expression was normal. According to immunofluorescence co-localization, the D622N mutation kept LDLR in the endoplasmic reticulum (ER). Di-LDL uptake tests showed that the G98S mutation could still bind and transport LDL normally. On the other hand, the W483* mutation had almost no LDLR expression or function, and the D622N mutation had ER-retained LDLR that could not bind or transport LDL. After 48 hours of treatment with 4 mM 4-phenylbutyric acid, some of the endoplasmic reticulum retention of D622N-mutant LDLR was alleviated. This facilitated its movement to the cell membrane, partially restoring its ability to bind and transport LDL. Conclusions: 4-phenylbutyric acid may serve as a potential therapeutic approach for FH patients with LDLR mutations causing ER retention.
Abstract 4142483: An Integrated Germline and Somatic Genomic Model Improves Risk Prediction for Coronary Artery Disease
Authors: Min Seo Kim, Xiong Yang, Md Mesbah Uddin, Tetsushi Nakao, So Mi Jemma Cho, Satoshi Koyama, Xinyu Zhu, Tingfeng Xu, Laurens Frans Reeskamp, Rufan Zhang, Zhaoqi Liu, Yunga A, Patrick Ellinor, Pradeep Natarajan, Minxian Wang, Akl Fahed
Journal: Circulation (2024)

Background: Multiple germline and somatic genomic drivers are associated with coronary artery disease (CAD), but their combined effects have not been thoroughly investigated. Hypothesis: An integrated model using all available information from single DNA biopsy including germline and somatic drivers improves CAD risk prediction. Methods: Based on whole genome sequencing data from UK Biobank, we curated familial hypercholesterolemia variants, clonal hematopoiesis of indeterminate potential, and leukocyte telomere length to calculate CAD polygenic risk score (PRS), proteome PRS, and metabolome PRS. An integrated genomic model (IGM) was developed by incorporating the six germline and somatic drivers for CAD. Results: Among 391,536 participants from UK Biobank (mean age 56.5 years; 53.8% women), 28,346 participants (7.2%) underwent incident CAD over a median follow-up of 12.3 years. The IGM showed better performance in predicting CAD risk (C-statistic 0.734, 95% CI 0.731 to 0.736) compared to the pooled cohort equations (PCE)(C-statistic 0.725, 95% CI 0.723 to 0.728). Addition of IGM to PCE further improved prediction accuracy (C-statistic 0.750, 95% CI 0.748 to 0.753) and resulted in a net reclassification improvement of 3.7% at risk threshold of 7.5%. IGM holistically captured CAD genetic risk, identifying individuals at high risk for CAD who do not have a single high-risk genomic factor but whose overall genomic profile places them at significant risk. Conclusions: We developed a state-of-the-art genomic model that integrates all available DNA information from a single biopsy. By accounting for the cumulative effects of multiple genomic drivers, IGM identifies high-risk individuals who might be overlooked by genomic risk models that rely on a single genetic factor.
Abstract 4142237: Atrial Arrhythmia Ablation in Myotonic Muscular Dystrophy Patients: A Single Institution Experience
Authors: Melissa Austin, Gregory Supple, Samuel Carrell, Lauren Elman, Saman Nazarian
Journal: Circulation (2024)

Introduction: Atrial fibrillation (AF) and atrial flutter (AFL) are commonly observed cardiac manifestations of myotonic muscular dystrophy (MMD). However, there is sparse data available describing the safety and efficacy of atrial ablation procedures in this population. Goals/Aims: This study aims to describe the safety and efficacy of AF or AFL ablation procedures in a cohort of MMD patients at a large, academic institution. Methods/Approach: All MMD patients who underwent AF or AFL ablations at a single institution between 2019 and 2023 were identified and analyzed using summary statistics. Results/Data: Between January 2019 and December 2023, ten patients with MMD underwent either AF or AFL ablation. Of these ten patients, 8/10 had type 1 MMD, 2/10 had type 2 MMD, and 3/10 were female. Median age at time of AF/AFL diagnosis was 34 years [IQR: 26, 48] and median age at time of ablation was 40 years [IQR: 30, 52]. All patients were on direct oral anticoagulants for &gt;3 weeks prior to and post ablation, 7/10 were on rate control medications and 5/10 were on rhythm control medications (2 class Ic, 3 class III). Indications for ablation included inappropriate ICD shocks in 3 patients, tachycardia-induced cardiomyopathy in 3 patients, arrhythmia-related symptoms in 3 patients, and patient preference in 1 patient. During the study period, 6/10 patients had cavotricuspid isthmus (CTI) AFL ablations, 2/10 patients had pulmonary vein isolation (PVI) ablations for AF, and 2/10 patients had simultaneous CTI and PVI ablations. No procedural complications were observed, though complications in the post-procedural period included aspiration pneumonia in 1 patient, aspiration and agitation necessitating prolonged intubation in 1 patient, and altered mental status prompting close observation and ultimately a negative stroke work-up in 1 patient. The majority of patients (7/10) had recurrent AF/AFL at a median 39 days post-ablation [IQR: 18, 270]. Four patients underwent a second AF or AFL ablation. Conclusion: Ablation of AF/AFL can be performed safely in MMD patients. However, anesthesia related complications and early recurrences of atrial arrhythmias warrant close consideration during evaluation for atrial ablation.
Abstract 4142598: Prognostic Value of Baseline and Change of Soluble Suppression of Tumorigenicity-2 in Light Chain Cardiac Amyloidosis
Authors: Anran Xin, Xinqing Li, Yan Huang, Xiaofeng Zhuang, Xuemei Zhao, Jinxi Wang, Ping Zhou, Jian Zhang, Yuhui Zhang
Journal: Circulation (2024)

Background: The predictive value of soluble suppression of tumorigenicity-2 (sST2) has been demonstrated in heart failure patients. However, studies on the association between baseline sST2 levels, dynamic changes in sST2, and prognosis in patients with light chain cardiac amyloidosis (AL-CA) are limited. Aim: The study sought to assess the predictive value of baseline circulating sST2 and added prognostic value of change in sST2 levels in patients with AL-CA. Methods: Patients diagnosed with AL-CA patients in Heart Failure Center, Fuwai Hospital between October 2015 to August 2023 were enrolled. The serum sST2 levels were measured at baseline and at 30 days. The change of sST2 (ΔsST2) was defined as the sST2 level at 30 days minus baseline sST2. The primary outcome was all-cause mortality. Kaplan–Meier analysis and Cox hazard models were performed to explore the predictive value of both sST2 at baseline and ΔsST2. Results: Overall, 132 patients were included. The median follow-up was 235 days. The mean age was 58.92 years (standard deviation [SD]: 10.74 years), and 62.1% of the participants were male. The median sST2 level was 30.42 ng/mL (IQR: 18.41–51.98 ng/mL), with the cutoff value set at 35 ng/mL. Higher sST2 levels at baseline (&gt;35ng/ml) were associated with increased risk of all-cause mortality after adjusting for N-terminal pro–B-type natriuretic peptide (NT-proBNP), cardiac troponin I (cTNI), and difference between involved and uninvolved free light chain (dFLC) levels (adjusted hazard ratio [HR] 1.86, 95% confidence interval [CI]: 1.03-3.38; P&lt;0.05). Among 40 patients with available ΔsST2, a total of 11 primary outcome events occurred. Patients who experienced these events exhibited higher levels of ΔsST2 (median: 193.55 ng/mL, IQR: 100.86-284.86 ng/mL) compared to those who did not (median: 8.04 ng/mL, IQR: -4.69-62.44 ng/mL). Moreover, higher ΔsST2 is also an independent indicator of worse prognosis, even after adjustment for baseline sST2, NT-proBNP, cTNI, and dFLC levels (adjusted HR 12.46, 95% CI: 1.26-123; P&lt;0.05). Conclusions: Elevated baseline sST2 blood level (&gt;35 ng/L) is a robust and independent indicator of prognosis in AL-CA patients. A dynamic increase in sST2 levels over the short term suggests a dismal prognosis.
Abstract 4142309: Development of novel 3D <i>in vivo</i> tracking of myofibroblasts and fibrosis with panoramic optical mapping after murine myocardial infarction
Authors: Pavithran Guttipatti, Najla Saadallah, Ruiping Ji, Elaine Wan
Journal: Circulation (2024)

Background: Myocardial infarction (MI) initiates an injury response that triggers fibroblast to myofibroblast cell transition and pathological fibrosis, a substrate for arrhythmogenesis. However, there are no methods to image in-vivo development of fibrosis continuously in the murine model other than cardiac MRI which is costly and time-consuming. Objectives: We aimed to develop a novel 3D method to track myofibroblast activity in the heart in vivo and correlate with electrophysiological changes using optical mapping. Methods: Mice with the alpha-Smooth Muscle Actin (α-SMA) promoter for expression of the red fluorescent protein DsRed were used to label myofibroblasts. MI was induced by left anterior descending artery ligation in α-SMA-RFP (n=4) and control C57BL/6 mice (n=5). RFP fluorescence was monitored over time using a PerkinElmer® In Vivo Imaging System (IVIS) before and after MI. 3D IVIS imaging with micro-computed tomography (CT) of 3D cardiac structure was then performed. Ex-vivo heart imaging of RFP followed by 3D panoramic optical mapping of electrical activation via Di-4-ANEPPS was performed and action potential duration (APD) maps generated. Results: After MI α-SMA-RFP mice demonstrate strong myofibroblast RFP signal localized above the heart on IVIS imaging at varying time points from 9 days to 3 months after MI. Myofibroblast RFP signal is not present before MI, and is also absent in control C57 mice. Ex-vivo imaging of hearts confirms myofibroblast RFP signal correlates with the site of infarction as well as increased APD. In α-SMA-RFP mice myofibroblast RFP intensity at the fibrotic infarct site is significantly greater than non-infarcted sites (mean difference 52.9 ± 13.2, p = 0.0088). Control C57 hearts do not demonstrate preferential RFP signal at infarct sites (mean difference -3.28 ± 2.99, p = 0.29). Furthermore, 3D IVIS imaging with CT co-registration demonstrates the localization of RFP signal in space near the heart. Conclusion: IVIS imaging of α-SMA-RFP is able to track myofibroblast activity in living mice up to three months after MI, and can be combined with optical mapping to study electrophysiology (APD, phase, activation maps). This novel approach can offer a method to monitor myofibroblast dynamics in disease states and test treatments that reduce the pathologic myofibroblast persistence that leads to fibrosis, scarring and arrhythmogenesis.
Abstract 4142200: An Economic Evaluation of Non-HDL-Cholesterol and Apolipoprotein B as Treatment Targets for Lipid-Lowering Therapy in Primary Prevention
Authors: Samuel Luebbe, John Wilkins, Andrew Moran, Allan Sniderman, Ciaran Kohli-Lynch
Journal: Circulation (2024)

Introduction: Apolipoprotein B (ApoB) is a better marker of residual risk for cardiovascular disease in patients treated with lipid-lowering therapy (LLT) than low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). However, it is unclear if treating to an apoB target is more cost-effective than treating to an LDL-C or non-HDL-C target. Methods: We used the CVD Policy Model, a validated computer simulation model, to estimate the clinical and economic outcomes associated with atherogenic lipid targets for LLT in a cohort of statin-eligible and ASCVD-free U.S. adults. We considered non-HDL-C, and apoB targets for intensification of LLT. Treatments considered were intermediate-intensity statin therapy, high-intensity statin therapy, and ezetimibe, intensified in that order. Upon entering the model, all individuals commenced statin therapy. Under ‘usual care,’ patients with LDL-C ≥100 mg/dL after three months of treatment were escalated to higher-intensity treatment. Under non-HDL-C and apoB testing strategies, LLT was escalated if patients had non-HDL-C ≥119 mg/dL and apoB ≥78.7 mg/dL, respectively, based on percentile equivalence to the LDL-C target. The primary outcomes for our study were healthcare costs (2023 U.S. dollars) and quality-adjusted life years (QALYs). Secondary outcomes were CVD events prevented and life years gained. A lifetime horizon was adopted with a health sector perspective. Future costs and QALYs were discounted at 3% annually. Results: In a sex-balanced simulated cohort of 500,000 individuals, both non-HDL-C and apoB testing produced more QALYs and fewer costs than usual care (LDL-C target). Intensification based on apoB, produced 1,416 more QALYs than non-HDL-C-guided intensification, saving around $29,300,000 over the lifecourse of the simulated cohort. Compared to non-HDL-C testing, apoB testing would lead to 1,233 fewer CVD events and 3,800 more life years. Health gains were greater for men, though apoB screening was cost-saving (i.e., higher QALYs, lower cost) when compared to LDL-C and non-HDL-C testing for men and women. Conclusion: Making LLT intensification decisions based on apoB instead of LDL-C or non-HDL-C would save costs while improving population health.
Abstract 4142557: Relationship between levels of nitric oxide (NO) concentration and flow-mediated vasodilatation test (FMD) in endothelial dysfunction development in overweight pregnant women with chronic hypertension.
Authors: Mokhinur Sadulloeva
Journal: Circulation (2024)

Background: In Central Asia, hypertension accounts for 14.5% of all maternal deathsThe problem of assessing endothelial dysfunction in women with hypertensive disorders during pregnancy are one of the early predictors of cardiovascular events. Objective: to determine the relationship between endothelial dysfunction and levels of nitric oxide (NO) concentration and flow-mediated vasodilatation (FMD) in overweight pregnant women with CHT. Methods: The study included 55 pregnant women of the I-II gestation period, divided into 2 groups. First group (n=34) included healthy pregnant women (healthy group). Second group (n=24) consisted of pregnant women with chronic hypertension/CHT. A physical examination was performed, heart rate was assessed, blood pressure was measured according to Korotkov method, body mass index (BMI) was calculated. Endothelial function was analyzed using a flow-mediated dilation (FMD) test by using ultrasound system Simens Acuson X700 and the level of nitric oxide (NO) concentration. NO level, which was determined by amount the main stable metabolites NO2 - and NO3 - were assessed by P.P. Golikov method. Results are presented as mean±SD. Statistical processing was carried out using the Statistica 13.0 program. P &lt; 0.05 was considered statistically significant. Results: It was revealed that there was no significant difference in the age of women (27±3.4 in 1 group vs 29±4.5 in 2 group, P = 0.0658) and number of pregnancies between groups (3.3±1.2 in 1 group vs 3.2±1.6 in 2 group, P = 0.7920). The average level of blood pressure in the group with CHT amounted to systolic blood pressure (SBP) of 153.83±16.43 mmHg. vs 102.72±10.42 mmHg in group 1 (P &lt;0.0001), according to diastolic blood pressure (DBP) 96.16±7.62 mmHg. vs 64.77±5.9 mmHg. in 1st group (P &lt;0.0001). Heart rate in group 1 was 89.8±12.2 beats/min and in group 2 93.5±13.8 beats/min (P=0.22). At the same time, 23 pregnant women (95.8%) with CHT were overweight, of which 15(62.5%) were women with obesity of the I and II degree. In the healthy group, there were only 7 women (16%) who were overweight, and no obese women were identified. The mean value of FMD for 1 group was 6.2±3.5% vs 4.82±1.02 (P &lt;0.0001), meanwhile NO – 8.8±0.281 µmol/l in group 1 vs NO – 13.7±0.517 µmol\l (P &lt;0.0001). Conclusion: In conclusion, FMD measured by using an ultrasound system and determination of the blood serum NO level is associated with early diastolic dysfunction in overweight pregnant women with CHT.