tbuckley/cabot-search huggingface dataset:
Abstract 12010: Index Patients With Hypertrophic Cardiomyopathy and a Normal Genetic Investigation of Recognized HCM Genes Do Rarely Have Affected Relatives
Authors: Soren K Nielsen, Frederikke G Hansen, Thomas A Fischer, Trine Madsen, Ib C Klausen, Dorthe S Møller, Morten S Jensen, Jens F Lassen, Torsten Bloch B Rasmussen, Jens Mogensen
Journal: Circulation (2021)

Introduction: The occurrence of hypertrophic cardiomyopathy (HCM) in relatives to HCM index patients with a normal genetic investigation of recognized HCM genes is largely unknown. It was the aim to determine the number of relatives with HCM among index patients with a normal genetic investigation. Methods: Clinical and genetic investigations were performed in consecutive index patients with HCM. Genetic investigations by next-generation sequencing were made in 116 recognized and likely HCM genes, and sequence variants were classified according to American College of Medical Genetics and Genomics criteria. First-degree relatives were invited for clinical investigations, including echocardiography and ECG-recording. Results: A total of 453 HCM index patients underwent clinical and genetic investigations, of whom 60% (270/453) did not carry pathogenic/likely pathogenic variants. Clinical investigations in 751 of their relatives identified 38 relatives (5%) who fulfilled HCM diagnostic criteria, and during five years of follow-up, two relatives developed HCM. In 88% of families (237/270), no relatives were affected. Affected relatives were older than healthy relatives, (56 years vs. 44 years p&lt;0.01), characterized by more comorbidity in terms of treatment for hypertension (31% vs. 18% p=0.05) and more frequently had coronary heart disease (14% vs. 1% p&lt;0.01). Risk calculations of sudden cardiac death were low (&lt;4%/5 years) in 76% (29/38) of affected relatives based on the European Society of Cardiology recommendations. Six relatives were considered at high risk of SCD and received a prophylactic implantable cardioverter-defibrillator (ICD), but none experienced any ICD shock therapy. Adverse events were observed in four affected relatives; three experienced SCD, and one developed end-stage heart failure. Conclusions: HCM index patients with normal genetic investigations rarely had affected relatives. Those affected were older at disease onset and had more comorbidity, suggesting that inheritance is polygenic/multifactorial. Discontinuation of follow-up could be considered in unaffected families, as disease development among healthy relatives was rarely seen, and few experienced adverse disease complications and sudden death.
Abstract 13918: Prognostic Implication of Mitral Valve Disease in Patients With Hypertrophic Cardiomyopathy
Authors: Dae-Young Kim, Jiwon Seo, Iksung Cho, Geu-Ru Hong, Jong-Won Ha, Chi Young Shim
Journal: Circulation (2021)

Introduction: Hypertrophic cardiomyopathy (HCM) is a genetic disorder affecting not only the myocardium, but also the mitral valve (MV) and its apparatus. Hypothesis: MV disease would have a prognostic implication in patients with HCM. Methods: We reviewed MV function and structure in the indexed echocardiograms of 1,185 HCM patients (60 ±14 years, men 67%) who were included in a single-center longitudinal HCM registry. Patients were classified as obstructive (n=104) or non-obstructive (n=1,081) HCM. Clinical outcomes were defined as a composite of cardiovascular death, heart failure hospitalization, MV surgery or septal myectomy, and heart transplantation. Results: Overall, 278 patients (23.5%) showed at least mild mitral regurgitation (MR) on their indexed echocardiogram (Figure 1-1). MR, systolic anterior motion (SAM), and mitral annular calcification (MAC) were more prevalent in patients with obstructive HCM than in those with non-obstructive HCM. During a mean of 7.0 ± 4.0 years’ follow-up, Kaplan-Meier plots revealed that patients with MR showed poorer clinical outcomes (21.6% vs.7.3%, log-rank p &lt; 0.001) than those without MR (Figure 1-2). A multivariate Cox model revealed that MR was independently associated with clinical outcome (hazard ratio 1.57, 95% confidence interval 1.04-2.35, p=0.030) along with female sex, chronic kidney disease, atrial fibrillation, obstructive type HCM, and diastolic dysfunction. Conclusions: MV disease is not uncommon in patients with HCM. MR, SAM, and MAC are more prevalent in patients with obstructive HCM. The presence of MR is associated with a poor prognosis in patients with HCM.
Abstract 12255: Prognostic Signals From Moderate Aortic Valve Disease: An Artefact of DICOM Structured Reporting?
Authors: Jonathan Sen, Ryan Moxham-Smith, Thomas Marwick
Journal: Circulation (2021)

Background: The use of Big Data in cardiac imaging research is usually based on DICOM structured reporting (SR) files. Default export settings from SR include all measurements, which may be misleading when diagnosis is based on peak measures. Validation of research datasets and remeasurements are seldom performed. We hypothesized that use of DICOM-SR outputs may lead to misclassifying patients with severe aortic stenosis (AS) as moderate. Methods: AS cases were filtered from an echocardiography dataset based on aortic valve area (AVA) &lt;2 cm 2 , and peak velocity (V max ) &gt;2 m/s. Data validation was conducted i) by verifying each parameter, ensuring only appropriate values were considered and peak gradients acquired, and compared with ii) remeasurement. Outlier and erroneous captured values were excluded. Values of each parameter and definitions of AS were compared pre- and post-validation and remeasurements. Results: Of 919 validated echocardiograms with moderate or severe AS, up to 60% of echocardiographic parameter values, such as AVA, mean and peak gradient, or dimensionless severity index (DSI) had minimum 10% error pre- and post-validation (Table). Based on 2 of 5 criteria (AVA, AVAi, V max , MPG, and DSI) for classifying AS severity, 42% of echocardiograms changed degree of AS severity. Among echos identified as moderate AS pre-validation, 173/413 (41%) were reclassified as severe AS. The main reason for erroneous data was averaging of all repeated echo measures. These differences exceeded changes due to remeasurement in a subgroup of 262 echocardiograms by an order of magnitude (Table). Conclusions: Non-peak data in DICOM-SR led to incorrect categorisation of a high proportion of patients based on AS severity definitions. Standardisation of data fields, and curation to ensure that only peak values are considered in DICOM-SR data are essential. Table . Differences in echocardiographic parameters pre- and post-validation of DICOM-SR or remeasurement
Abstract 13202: The Accuracy Of EMS Dispatch For Stroke Following The Introduction Of The Stroke Diagnostic Tool
Authors: Janet Bray, Hannah Webster, Ziad Nehme, Kathryn Eastwood, Karen Smith, Kate Cantwell, Judith Finn, Christopher Bladin, Peter Cameron
Journal: Circulation (2021)

Introduction: Early identification of stroke in the emergency call is key to timely reperfusion therapy. The Medical Priority Dispatch System (MPDS) is widely used and recent versions include a Stroke Diagnostic Tool (SDxT) using the FAST (Face, Arm, Speech) assessments. We conducted a retrospective observational study to examine whether introduction of the SDxT improved the identification of stroke/TIA in the emergency call in Victoria, Australia. Methods: We included all stroke dispatches (MPDS Code 28) for adults (aged ≥20 years) between 2008 and 2015. We linked this data to diagnoses from Ambulance Victoria, and the Victorian Department of Health and Human Services’ databases: the Victorian Emergency Minimum Dataset and the Victorian Admitted Episode Database. We examined the use of SDxT codes, and compared the proportion of stroke/TIA diagnoses before and after the introduction of the SDxT in September 2013. Results: Over the study period there were 108,917 Code 28 cases (average 13,600/year), 80% (n=86,906) were transported to an ED and 55% (n=60,334) were admitted to hospital. There were 3,141 diagnoses among the Code 28 cases, with 30% diagnosed with stroke/TIA. No changes was seen in the proportion of stroke/TIAs after the introduction of the SDxT (28.5% vs. 28.2%, p=0.23). The SDxT was used and complete in 63% (n=20,070) of calls. Patients with evidence of stroke on the SDxT were more likely to have stroke/TIA (partial evidence=29%, strong evidence=38% and clear evidence=40%) compared to those with no evidence (20%) and those with no/incomplete SDT (25%). Conclusions: Our results suggest a large proportion of stroke dispatches are not stroke/TIA, but evidence of stroke on the SDxT does identify marginally higher proportions. Further research is required to understand use of the tool, and public education on stroke assessments may be needed to realise its full potential.
Abstract 11758: Prevention of Radiation-Induced Coronary Microvascular Leakage by the Restoration of an Endothelial Tight-Junction Protein
Authors: Sarmila Nepali, Shirley Xu, Swati D Sonkawade, Umesh C Sharma, Saraswati Pokharel
Journal: Circulation (2021)

Introduction: In cancer survivors exposed to ionizing radiation (IR) exposure to the chest and heart, coronary endothelial injury and disruption of vascular barrier integrity is noted. The mechanisms driving the IR-induced leakiness of the coronary microvasculature are not known. There is no therapy to prevent such injury. Hypothesis: IR exposure downregulates a tight junction protein claudin-1 (cldn1), which can lead to altered endothelial barrier integrity. Ac-SDKP, an endogenous peptide, prevents cldn1 loss and preserves coronary vascular barrier function. Methods: We tested the constitutive and physiological effects of cldn1 both in vitro and in vivo . Human coronary vascular endothelial cells (HMVECs) lacking cldn1 by siRNA silencing were used for loss-of-function studies. Newly developed vascular-specific (VE-cadherin promotor-linked) cldn1 overexpressing transgenic (TG) mice were used for cldn1 gain-of-function studies. Mice were exposed to 45Gy chest radiation in fractionated doses (3Gy/day). A subgroup of irradiated mice was treated with Ac-SDKP (3.2mg/kg/day) for 3-weeks. Evans blue dye was injected via tail-vein 30 mins before euthanasia and dye extravasation through coronary microvasculature was quantified. Cldn1 expression was examined by Western blot and in vitro cell permeability was examined by FITC-dextran permeability assays. Results: Cldn1 silencing with siRNA showed increased permeability in HMVECs (control, 1.0±0.01, siRNA, 1.3±0.01; p=0.0002). Cardiac irradiation significantly decreased myocardial cldn1 (control 1.0±0.27, IR 0.45±0.31; p=0.001). Consequently, there was a significant increase in myocardial Evans blue dye extravasation compared to controls (control 1.0±0.22, IR 1.3±0.23, p=0.039). Cldn1 overexpression mice had decreased dye extravasation compared to WT controls (WT 1.0±0.23, TG 0.38±0.27 p=0.002). Ac-SDKP restored cldn1 protein expression, and inhibited dye leakage in the myocardium after IR exposure (0.57±0.21, p=0.048 vs IR). Conclusions: Our study shows that IR exposure induces endothelial barrier disruption through a reduced expression of endothelial tight-junction protein, cldn1. Ac-SDKP prevents these effects, at least in part, by preventing loss of claudin-1.
Abstract 10556: A Systematic and Reliable Process for Performing Cost Containment Analysis Within the Operating Room
Authors: Joseph R Nellis, Neel Prabhu, James M Meza, Nicholas D Andersen, Joseph W Turek
Journal: Circulation (2021)

Purpose: Healthcare spending within the United States increased 4.6% in 2019 and represented over $3.8 trillion, or 17.7% of our GDP. The operating margin for most hospitals is 1-3%. As costs continue to rise, insurers will continue to shift these financial risks and responsibilities onto hospitals and hospitals eventually onto surgeons. Methods: Using a recently introduced surgical receipt function within Epic, we set out to develop cost containment strategies within congenital cardiac surgery at Duke University Hospital. Surgical receipt data was obtained between January 1, 2020 and January 1, 2021. Variability in case costs and product utilization were identified. Findings were discussed with surgeons to identify high impact changes with low barriers to implementation. Results: Between January 1, 2020 and January 1, 2021, there were 340 index cases and 449 unique surgical receipts. Four procedures representing 54 patients accounted for more than 50% of the total annual direct operating room supply costs (LVAD, 5 patients, 22.7% of annual costs; Norwood, 20 patients, 12.7%; RV-PA shunt, 16 patients, 9.9%; PVR, 13 patients, 9.4%). Exploration chest for postoperative hemorrhage was associated with the highest variability in case cost. In addition to mechanical devices and valves, cost drivers included the use of disposable vascular clips, suture brand preference between surgeons, and surgical patch material utilization which accounted for 3.7%, 6.6%, and 26.5% of overall annual direct operating room supply costs. Conclusions: We project 6-6.5% in annual savings due to changes in suture and surgical clip utilization. Changes to surgical patch utilization should carry an additional 4-4.5% in savings. The surgical receipt represents a reliable and uniform way of reporting surgical costs with broader implications for all surgical subspecialties.
Management of Advanced Pulmonary Sarcoidosis
Authors: Rohit Gupta, Marc A. Judson, Robert P. Baughman
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

The term "advanced sarcoidosis" is used for forms of sarcoidosis with a significant risk of loss of organ function or death. Advanced sarcoidosis often involves the lung and is described as "advanced pulmonary sarcoidosis" (APS), which includes advanced pulmonary fibrosis, associated complications such as bronchiectasis and infections, and pulmonary hypertension. Although APS affects a small proportion of patients with sarcoidosis, it is the leading cause of poor outcomes, including death. Here we review the major patterns of APS with a focus on the current management as well as potential approaches for improved outcomes for this most serious sarcoidosis phenotype.
Abstract 11418: Fibrosis and Calcium Signaling Regulation Are Critical Mechanisms in a Three-Hit HFpEF Mouse Model
Authors: Yijia Li, Xiaoying Zhang, jianguo jin, Jeffery Molkentin, Steven R Houser, Xiongwen Chen
Journal: Circulation (2021)

Introduction: There is a lack of animal models of heart failure with preserved ejection fraction (HFpEF). Hypothesis: A mouse model with increased Ca2+ influx receiving a high-fat diet (HFD) and L-NAME (3 hits) could be a model for HFpEF to help reveal the mechanism. Methods: Cardiomyocyte (CM) specific, inducible Cavβ2a low expression transgenic (Cavβ2a LE TG) and their control littermate mice were fed with either chow diet (LC and CC), HFD+L-NAME (LHLn, CHLn), or HFD+L-NAME+SAHA (LHLnS, CHLnS) since the age of 4months for 6 months. Echocardiography had been done monthly. Hemodynamic analysis, histological analyses, and Western blotting (WB) had been used to figure out the possible mechanisms after euthanization. Results: LHL (3 hits) mice had preserved left ventricular ejection fraction (LVEF) but the highest levels of ANP/BNP and the lowest strain rate. 3-Hit led to obvious diastolic dysfunction indicated by a higher ratio of mitral E wave to mitral annulus e’ velocity (E/e’ ratio), ventricular stiffness index, end-diastolic pressure, and left atrial (LA) dilation rate (90% in LHL mice). LA and LV fibrosis were more severe in the LHL group. Fibrosis-related molecules, including lysyl oxidase, Periostin, transforming growth factor-beta and its downstream transcription factor SMAD2/3 were higher in the LHL group. LHL mice also had lower PLB phosphorylation at Thr17, less SERCA, more NCX, and increased TnI phosphorylation. SAHA treatment could significantly reverse the HFpEF phenotype. Conclusions: 3-Hit is a model for HFpEF, which can be reversed by SAHA treatment. Fibrosis and altered Ca2+ signaling are critical underlying mechanisms for HFpEF.
Multilevel factors predict medication adherence in rheumatoid arthritis: a 6-month cohort study
Authors: Alejandro Balsa, Maria Jesus García de Yébenes, Loreto Carmona
Journal: Annals of the Rheumatic Diseases (2021)

Non-adherence challenges efficacy and costs of healthcare. Knowledge of the underlying factors is essential to design effective intervention strategies.To estimate the prevalence of treatment adherence in rheumatoid arthritis (RA) and to evaluate its predictors.A 6-month prospective cohort study of patients with RA selected by systematic stratified sampling (33% on first disease-modifying rheumatic drug (DMARD), 33% on second-line DMARD and 33% on biologics). The outcome measure was treatment adherence, defined by a score greater than 80% both in the Compliance Questionnaire in Rheumatology and the Reported Adherence to Medication scale, and was estimated with 95% CIs. Predictive factors included sociodemographic, psychological, clinical, drug-related, patient-doctor relationship related and logistic. Their effect on 6-month adherence was examined by multilevel logistic models adjusted for baseline covariates.180 patients were recruited (77% women, mean age 60.8). The prevalence of adherence was 59.1% (95% CI 48.1% to 71.8%). Patients on biologics showed higher adherence and perceived a higher medication need than the others; patients on second-line DMARDs had experienced more adverse events than the others. The variables explaining adherence in the final multivariate model were the type of treatment prescribed (second-line DMARDs OR=5.22, and biologics OR=3.76), agreement on treatment (OR=4.57), having received information on treatment adaptation (OR=1.42) and the physician perception of patient trust (OR=1.58). These effects were independent of disease activity.Treatment adherence in RA is far from complete. Psychological, communicational and logistic factors influence treatment adherence in RA to a greater extent than sociodemographic or clinical factors.
Nationwide Laboratory Network for AML Cross-Validated NGS Studies: Results from a Real-Life Cohort of the Pethema Group
Authors: Claudia Sargas, Rosa Ayala, Carmen Chillon, Maria Jose Larrayoz, Estrella Carrillo, Cristina Bilbao, Manuel Yébenes, Marta Llop, Inmaculada Rapado, Ramon Garcia-Sanz, Iria Vazquez, Elena Soria, Santiago Sánchez-Sosa, Kamila Janusz, Carmen Botella, Josefina Serrano, David Martinez-Cuadron, Juan-Miguel Bergua, Maria Luz Amigo, Pilar Martinez Sanchez, Mar Tormo, Teresa Bernal, Pilar Herrera-Puente, Raimundo García-Boyero, Lorenzo Algarra, Maria Jose Sayas, Lisette Costilla-Barriga, Esther Pérez-Santolalla, Inmaculada Marchante, Esperanza Lavilla-Rubira, Víctor Noriega, Juan Manuel Alonso Dominguez, Miguel A. Sanz, Joaquín Sánchez, María Teresa Gómez-Casares, Jose A. Perez-Simon, María José Calasanz, Marcos González, Joaquín Martínez-López, Eva Barragán, Pau Montesinos
Journal: Blood (2021)
Abstract P435: Probiotic Supplements Could Prevent Diet-induced Mitochondrial Dysfunction In The Liver Hepatocytes Of Apolipoprotein-e Knockout Mice
Authors: Antoine J St-Amant, Lise Cougnaud, Dajana Vuckovic, Andreas Bergdahl
Journal: Circulation Research (2021)

A poor diet can modify the intestinal microbiota, known as gut dysbiosis, which causes hepatocyte mitochondrial dysfunction through the release of endotoxins in the portal vein. Mitochondrial dysfunction in the liver leads to non-alcoholic fatty liver disease (NAFLD). Epidemiological evidence shows that most deaths from NAFLD are related to cardiovascular diseases (CVD) demonstrated by impaired vasodilatation as well as increased arterial stiffness, calcification, inflammation, and intimal-medial thickness. Therefore, the objective of our study was to investigate the potential of probiotic supplements to prevent a diet-induced mitochondrial dysfunction in hepatocytes. Apolipoprotein-E knockout mice—genetically modified animals that develop dyslipidemia—were placed in 3 diet groups including a control, western style (high in fats and carbohydrates), as well as a low-carbohydrate high-protein diet. Each group was then further divided in 3 subgroups based on the dose of probiotics administered, including a control, low (0.5 B/dose) and high (5 B/dose) dose of probiotics, for a total of 9 groups (n= 8-12 animals/group). The probiotic supplements contained a 1:1 ratio of Lactobacillus Helveticus and Bifidobacterium Bifidum . The bodyweight and water intake were monitored weekly. After 6 weeks, the liver mitochondria were analyzed by high resolution respirometry using a sequential substrate addition protocol (malate, octanoylcarnitine, ADP, glutamate, pyruvate, cytochrome C, succinate and FCCP) to investigate mitochondrial maximal respiration, leak, membrane damage and uncoupling. Our preliminary results show that the groups that received a high dose of probiotics gained less weight, had a higher respiration following the addition of ADP (a biomarker of complex V efficiency) and a lower respiration following FCCP (a biomarker of mitochondrial uncoupling), as compared to control. Supplements of probiotics could promote weight loss and prevent a diet-induced mitochondrial dysfunction in liver hepatocytes, an important risk factor for NAFLD and therefore, CVD. This project could translate into future research directions in preventative medicine, for example by investigating the potential of probiotics in the prevention of mitochondrial dysfunction in other organs, including the heart and the vascular system.
Single-Cell RNA Sequencing Analysis Reveals Mechanisms of Initiation and Progression in Chronic Myelomonocytic Leukemia
Authors: Guillermo Montalban-Bravo, Feiyang Ma, Irene Ganan-Gomez, Rashmi Kanagal-Shamanna, Vera Adema, Yue Wei, Kelly S. Chien, Natthakan Thongon, Hui Yang, Carlos E. Bueso-Ramos, Hagop Kantarjian, Guillermo Garcia-Manero, Simona Colla
Journal: Blood (2021)
Abstract 14075: Infective Endocarditis Associated With Irreversible Coronary Spasm and Cardiac Arrest
Authors: Mohammad ALTermanini, Mohamed Abdelghani, Mhd Baraa Habib, Mohanad Shehadeh, Mohamed Magdi, Ashraf Ahmed, Maab Elhaj, Abdulrahman Arabi
Journal: Circulation (2021)

Introduction: Coronary artery spasm (CAS) can elicit ischemia with transient ST-segment deviation that usually responds to nitrates; however, CAS can precipitate arrhythmias leading to sudden cardiac arrest. Infective endocarditis (IE) is associated with the acute coronary syndrome (ACS) usually via coronary embolism and compression secondary to peri-annular complications. CAS in association with IE causing ACS is extremely rare. Case: A 54-year-old man had a recent ST-elevation (STE) myocardial infarction, which required stenting to obtuse marginal artery (OM2) artery. He presented with a fever for one week. A new diastolic murmur at the aortic area on examination. Echocardiography showed a bicuspid aortic valve with perforation and new-onset aortic regurgitation suggestive of vegetation. Diagnosis of infective endocarditis was established, and the patient was started on medical treatment and was being prepared for surgical repair. During the hospital stay, he had recurrent episodes of severe chest pain accompanied by transient STE on ECG but normal troponin level. It was always responding to sublingual nitrates. CT coronary Angiogram showed no significant coronary stenosis and patent stent in OM2. The patient had again an attack of severe chest pain with ECG showed extensive STE then he developed pulseless electrical activity. Result: Resuscitation was started and emergency coronary angiography was performed and showed severe spasms in both LAD and LCX with TIMI-1 flow. A repeated image during resuscitation showed patent arteries with TIMI-III flow. A prolonged CPR in Cath-lab failed and the patient died. Although there was no clear explanation of the mechanism, the simultaneous association between the CAS and IE raises the suspicion of a possible relationship between both pathologies. Conclusions: Severe coronary spasm should be considered as a possible cause of ACS in association with IE.