tbuckley/cabot-search huggingface dataset:
Abstract 4143814: Utility of Echocardiography to Prognosticate Fetal High Cardiac Output States
Authors: Anissa Viveiros, Lisa Hornberger, Angela McBrien, Luke Eckersley
Journal: Circulation (2024)

Background: Fetal anemia can lead to high cardiac output (CO) failure, fetal hydrops and fetal demise. Intrauterine transfusion (IUT) is the standard of care, but carries risks of premature delivery and fetal death; therefore, it is critical to identify the most affected fetuses prior to intervention. Elevation of the peak systolic velocity in the middle cerebral artery (MCA-PSV) is routinely used to indicate intervention; however, the reported false positive rate is as high as 12 to 14%. Aim: Assess whether measured CO by fetal echocardiography (FE) can be used as a complementary screening tool to predict fetal anemia. Methods: We identified all pregnancies referred for FE from 2009-2023 with suspected fetal anemia (n=49). We reviewed FEs (n=88) to measure ventricular function, combined CO (aortic and pulmonary outflows), and measured ventricular dimensions. Percentiles for CO were used based on published normative data. The MCA-PSV was measured and reported as multiples of the median (MoM). Where available, pre-transfusion fetal hemoglobin (Hb) readings were reported as a MoM, with temporally matched FE studies performed prior to IUT included for analysis (n=8). Results: Overall , MCA-PSV was positively associated with left ventricular (LV) CO, but not with right ventricular (RV) or combined (CCO) (LV CO p=0.037, Figure 1A; RV CO p=0.790; CCO p=0.290). The LV CO correlated with z-scores for LV and RV end diastolic dimensions (EDD) (LVEDD p&lt;0.001; RVEDD p=0.018). The RV CO and CCO also were positively associated with LVEDD (p=0.004 and p&lt;0.001, respectively), and RVEDD (p=0.009 and p=0.003, respectively). However, the MCA-PSV did not correlate with ventricular dimensions (LVEDD p=0.524 and RVEDD p=0.689). Fetal Hb was negatively correlated with the MCA-PSV, which approached statistical significance (Figure 1B). Fetal Hb negatively correlated with the LV CO (Figure 1C), but not with RV CO or CCO (Figure 1D). Conclusion: Preliminary results suggest that fetal LV CO may confer additive value to current MCA-PSV measurement in predicting the severity of fetal anemia. Larger studies are warranted to explore the relationship of fetal LV CO and MCA-PSV with fetal Hb and prognosis in high output cardiac failure.
Abstract 4143965: Reactive Oxygen Species Scavenging Reduces Complex Fractionated Atrial Electrograms (CFAEs) In Persistent Atrial Fibrillation Patients - A New Smart Mechanism Guided CFAE Targeting Approach in Atrial Fibrillation
Authors: Markus Rottmann, Bradley Knight, Rod Passman, Rishi Arora
Journal: Circulation (2024)

Background: It is known that oxidative stress (OS) and complex fractionated atrial electrograms play an important role in AF. However, the effect of reactive oxygen species (ROS) on complex fractionated atrial electrograms (CFAEs) in persistent atrial fibrillation patients remains unsettled. While previous CFAE ablation studies have mixed results, it is currently also unclear which types of CFAEs should be targeted with ablation during the clinical electrophysiological (EP) study. Objective We hypothesized that ROS are dynamically involved in the creation of a vulnerable substrate leading to overlying CFAEs and that regions of CFAEs that may reflect high OS are uniquely sensitive to acute ROS scavenging with N-acetylcysteine (NAC) in persistent AF patients. Methods: We performed in 5 patients with persistent AF high-density mapping in the left and right atrium (LA, RA) pre/post-NAC (intravenous, dose 100mg/kg) (Figure 1A) using the HD-grid catheter (EnSite, Abbott) (Figure 1B). We analyzed cycle length (CL) and dominant frequency (DF), organization index (OI), fractionation index (FI), and regions demonstrating &gt;10% change in these parameters and CFAEs (definition EnSite) &gt;50% change post-NAC. Results: NAC (Figure 2) affected AF electrogram measures in atrial sub-regions, increasing CL in the left lateral free wall, right atrial free wall, affecting DF/OI preferentially in the left atrial superior wall and CFAEs (Figure 3A, B) in the left atrial inferior wall (Figure 3C). Acute administration of NAC caused significantly greater percentage changes in CFAEs in the LA (165%) pre vs post-NAC compared to percentage changes in CL (40%), DF (33%), OI (37%) and FI (16%) (P=0.002) (Figure 3D). 35% of all CFAEs in the LA and 21% in the RA were sensitive (&gt;50% change, P=0.02) to ROS scavenging. Conclusion: Acute administration of NAC organizes AF electrogram characteristics in subregions in the left and right atrium and has a greater effect on CFAEs in the left atrium compared to other established AF electrogram characteristics. About one third of all CFAEs are ROS dependent. These uniquely sensitive CFAE regions to ROS scavenging may constitute a new smart therapeutic target in patients with persistent AF.
Abstract 4143807: Risk of all-cause mortality after aortic valve replacement in 66,931 individuals across the VA Healthcare System
Authors: Aeron Small, Armando Saavedra, Serena Houghton, Kelly Cho, Laura Tarko, PETER WILSON, Xiangqin Cui, JASON LINEFSKY
Journal: Circulation (2024)

Introduction: Aortic stenosis is the most common valvular heart disease and is managed by aortic valve replacement (AVR) procedures. Comorbid conditions may impact survival after AVR. Methods: We evaluated risk factors for all-cause mortality after AVR in the Veterans Affairs (VA) healthcare system for individuals with an AVR between January 1 st 2007 and December 31 st 2017, with National Death Index mortality data through December 31 st , 2020. Clinical diagnoses and procedures were established by International Classifications of Disease (ICD) and Current Procedural Terminology (CPT) codes both in the VA and the Center for Medicare and Medicaid Services. Hazard rates for the primary outcome of all-cause mortality were calculated using a cox proportional hazards model adjusted for age at AVR, sex, and prevalent clinical risk factors (heart failure [HF], obesity, type 2 diabetes [T2D], and myocardial infarction [MI]). Results: There were 7,984,029 individuals seen regularly at the VA between 2007 and 2017. Within this group, there were 783,772 (9.8%) individuals with an established diagnosis of AS without prior valve replacement with a median (interquartile [IQR]) age of 73.5 [67.4-80.3] years, and 98% male. Between 2007-2017, 66,931 individuals had an AVR with median [IQR] age 72.8 [66.6-79.3] years, 98% male. Of the individuals with an AVR, 24,253 (36.2%) died prior to the end of follow up, with a median [IQR] time to death of 3.3 [2.8-5.3] years. At the time of valve replacement, there were 16,301 (24%) diagnoses of CKD, 11,916 (18%) diagnoses of HF, 21,575 (32%) diagnoses of T2D, and 4,211 (6%) diagnoses of prior MI. In a multivariable model, with adjustment for age, sex, and all clinical risk factors, a prevalent HF diagnosis portended the highest risk of all-cause mortality after AVR (HR 1.57 [1.52-1.62], p &lt; 0.001), followed by T2D (HR 1.13 [1.09-1.16], p &lt; 0.001), CKD (HR 1.11 [1.08-1.15], p &lt; 0.001), and MI (1.05 [0.99-1.11], p = 0.06). Conclusions: Common clinical comorbidities including HF, CKD, and T2D, but not MI independently increase the risk of all-cause mortality after AVR.
Abstract 4144027: AI-enabled multimodal risk stratification of probable transthyretin amyloid cardiomyopathy from point-of-care electrocardiography and ultrasound: A report from the TRACE-AI Study
Authors: Evangelos Oikonomou, Veer Sangha, Lovedeep Dhingra, Arya Aminorroaya, Aline Pedroso Camargos, Andreas Coppi, Edward Miller, Cesia Gallegos, Rohan Khera
Journal: Circulation (2024)

Introduction: Artificial intelligence (AI) tools may enable the detection of transthyretin amyloid cardiomyopathy (ATTR-CM) from 12-lead electrocardiographic (ECG) images and point-of-care ultrasonography (POCUS). The TRACE-AI study is designed to examine the burden and outcomes of potentially undiagnosed cases through the opportunistic deployment of multimodality AI algorithms. Research Question: To explore the burden and prognosis of probable ATTR-CM identified by opportunistically deployed AI-ECG and AI-POCUS in the emergency department (ED). Methods: Across a diverse, 5-hospital health system, we identified individuals never diagnosed with ATTR-CM who had previously sought care in the ED during 2013-2023 and had no history of heart failure (HF) at baseline. Among these, 17,564 individuals (median age 52 [IQR: 36-66] years; 9,407 [53.6%] women, 4,520 [25.7%] Black and 3,180 [18.1%] Hispanic) had undergone a 12-lead ECG and POCUS within one day of each other ( Fig. 1 ). We deployed validated AI algorithms for ATTR-CM from 12-lead ECG images and POCUS videos to obtain study-level probabilities of ATTR-CM. We stratified the population based on validated AI-ECG and AI-POCUS thresholds and examined the associations of screen positivity with mortality and HF hospitalization in Cox models adjusted for age, sex, hypertension, and diabetes mellitus. Results: Among 17,564 eligible individuals, 780 (4.4%) screened positive by AI-ECG, and 286 (1.6%) by both modalities. Over a median follow-up of 2.2 [IQR: 1.2-5.9] years, there were 1,226 deaths and 458 HF hospitalizations. Screen positivity on both modalities conferred a 1.7-fold higher adjusted risk of death (adj. HR 1.70 [95%CI: 1.31-2.22], Fig. 2A ) and 2.2-fold higher risk of HF hospitalization (adj. HR 2.18 [95%CI: 1.44-3.30], Fig. 2B ), compared with those screening negative on both modalities. Even among those screening positive on one modality, there was a significant 1.2-fold and 1.5-fold higher risk of death and HF hospitalization relative to the reference group ( Fig 2A-B ). Conclusions: Scalable AI technology applied to ECG images and POCUS as part of their ED care identified that ~1.6% of individuals screened positive for ATTR-CM on both modalities but without eventual clinical diagnosis. This group of patients with probable undiagnosed ATTR-CM had a higher risk of long-term adverse outcomes. This underscores the need for improving ATTR-CM diagnostic rates through scalable technology applied in routine care.
Abstract 4144024: AI-Enabled Photoplethysmography Can Help Detect Elevated Blood Pressure And Predict Near-Term Incidence Of Hypertension
Authors: Paolo Di Achille, Hao-Wei Su, Ho Ko, James Taylor, Jacqueline Shreibati, Matthew Thompson, Ming-Zher Poh
Journal: Circulation (2024)

Background: Improving detection of individuals with undiagnosed hypertension (HTN) and those at risk of developing HTN are global priorities. Sensors within smartphone and consumer devices capable of photoplethysmography (PPG) may provide novel tools to support these efforts. Aims: Determine risk of baseline elevated blood pressure (BP) and incident HTN using a deep learning model (AI-PPG-BP) derived from PPG waveforms. Methods: Using the UK Biobank dataset, participants aged 40-74 without previously known HTN or cardiovascular disease were split into train (N=58,216), tune (N=31,671), and test (N=44,684) sets based on location of the data collection site. We trained a 1D convolutional neural network incorporating age, sex, weight and height to estimate BP from PPG waveforms (obtained from a 10-15 second recording with an infra-red sensor). Performance of model-predicted BP (AI-PPG-BP) in detecting elevated BP at baseline was compared to a logistic regression model using risk factors of age, sex, BMI, parental HTN, and smoking status (RF-BP). Additionally, we developed a Cox proportional hazards model to predict 4-year incident HTN (AI-PPG-HTN), using AI-PPG-BP as well as the risk factors. Model performance for incident HTN was compared to a Cox model using risk factors alone (RF-HTN), as well as the Framingham HTN risk score. Results: In the test set, AI-PPG-BP detected elevated baseline SBP/DBP of &gt;140/90 (n=15,696, 35.1%) and &gt;160/110 mmHg (n=3,546, 7.9%) with AUROCs of 0.818 [95%CI: 0.814-0.822] and 0.867 [0.861-0.872], respectively, outperforming RF-BP (AUROC 0.696 [0.691-0.700] and 0.706 [0.698-0.714]). AI-PPG-BP stratified cumulative incidence of HTN, and was significantly associated with risk of incident HTN (HR per SD: 1.48 [1.41-1.54], p&lt;0.001) after adjusting for risk factors. The c-statistic for AI-PPG-HTN (0.733 [0.725, 0.741]) outperformed RF-HTN (0.711 [0.703, 0.721]); and was non-inferior to the Framingham HTN risk score (0.736 [0.728, 0.745]; prespecified non-inferiority margin 0.010, p&lt;0.01). Conclusion: A deep learning model, AI-PPG-BP, may be able to serve as a useful pre-screener by helping to detect elevated BP and stratifying risk of near-term, incident HTN using finger PPG.
Abstract 4143849: The Impact of Community Health Workers in a Pre-existing Postpartum Hypertension Program
Authors: Marly Azzi, Courtney Bisson, Arin Everett, Sanela Potchileev, Ariel Mueller, Colleen Duncan, Sarosh Rana
Journal: Circulation (2024)

Background: Maternal mortality in the United States continues to rise, with hypertensive disorders of pregnancy (HDP) playing a significant role in adverse outcomes. Patients of color have worse outcomes compared to their White counterparts. Data in non-pregnant patients suggests community health workers (CHWs) can help mitigate disparities and improve HDP outcomes. Does exposure to a CHW improve patient education about HDP and satisfaction and are these findings different between Black and non-Black patients? Methods: This was a prospective survey study that enrolled patients delivering at the University of Chicago (UCM). Patients with HDP are automatically enrolled in a standardized postpartum hypertension education program (STAMPP-HTN) where they receive education and a blue tooth compatible blood pressure monitor. Patients who did not record their blood pressures were contacted by a CHW and surveyed about their experience. Results were compared between Black and Non-Black patients using a Wilcoxon Rank Sum, X 2 or Fisher’s Exact test, as appropriate. Results: There were 32 survey responses from 22 respondents and 15 patients with complete baseline data, 6 of whom were Black and 9 of whom were non-Black. There were no differences in age, insurance status, or pregnancy outcomes between groups. Additionally, of the 32 survey responses, there were no significant differences in experiences with a CHW between Black and non-Black patients. Table 1 outlines the impact of CHW on patient’s education and attitude towards HDP. Most patients found that CHW involvement increased the amount of time they checked their blood pressure (76%) with no difference between races (p=0.23). Overall, 84% patients (strongly agreed or agreed) that their CHW knows the important issues about their healthcare. Conclusion: The incorporation of a CHW program into a pre-existing postpartum hypertension program was overall well-received by patients with no racial disparity. The program increased the patient’s understanding of HDP and lead to a better follow up of their blood pressures values. Further work is needed to determine how this program impacts long-term patient’s outcomes.
Abstract 4143888: Exploring the Perspectives and Journey of Patients Utilizing Left Ventricular Assist Devices as They Approach End-of-Life: A Cross-sectional Study
Authors: Jessica Thompson, Devan Costelle, Debra Moser
Journal: Circulation (2024)

Background: Over the past decade over 27,000 patients have been implanted with a left ventricular assist device (LVAD) for the treatment of advanced heart failure (HF). Technology has advanced greatly over this time with 1-year mortality rates around 14% for the newer devices. Up to 75% of the HF population is thought to have mild cognitive impairment, which is related to increased readmission rates and higher mortality. Guidelines provided by professional organizations encourage providers to discuss end-of-life situations with LVAD patients and their caregivers. Purpose: The purpose of this study was to explore the attitudes and experiences of patients with an LVAD related to end-of-life situations and pump exchanges, and to identify if mild cognitive impairment impacts end-of-life decision-making. Methods: A cross-sectional, correlational study design was used, with 30 LVAD patients completing an end-of-life questionnaire and a validated cognitive assessment instrument. Results: The average age of the participants was 57±16, 77% male, 90% identified as white, non-Hispanic, and 63% were labeled as destination therapy. Fifty-eight percent of the cohort had discussed end-of-life scenarios with a healthcare provider, and 60% had discussed what a pump exchange involved. Forty-four percent of the total cohort indicated they never wanted to have a conversation about end-of-life with their provider and 73% said they would have a pump exchange even if they were seriously ill and were dying of a terminal illness other than heart failure. Of the 29 patients who were able to complete the cognitive assessment, 79% met criteria for mild cognitive impairment. There were no differences in the experiences and attitudes regarding end-of-life between those with mild cognitive impairment, and those with normal cognition. Conclusion: Despite having higher mortality rates in the HF population, those with mild cognitive impairment had similar experiences and attitudes regarding end-of-life. There are still many misconceptions regarding decision-making related to the end-of-life and pump exchange for patients with an LVAD, and moving forward it is important to identify factors that may influence these decision-making processes.
Abstract 4143917: Novel Precision Cardiology Treatment for PRKAG2 Cardiomyopathy, a Subset of Patients with Wolff-Parkinson-White Syndrome
Authors: Maria Azzurra Missinato, Kellie Lemoine, Giang Ho, Joshua Fong, Jie Wang, Sami Abdulkadir, Aaron Yu, Maryam Jordan, Sydney Kasmer, Nathaniel Delos Santos, Qingying Meng, Maria Hedlund, Son Lam, Yiming Zhu, Sharon Paige, Eileen Blasi, Georgios Karamanlidis
Journal: Circulation (2024)

Background: PRKAG2 syndrome is an inherited disease caused by mutations in the PRKAG2 gene, which encodes the γ2 regulatory subunit of AMP-activated protein kinase (AMPK). These mutations result in increased AMPK activity leading to aberrant myocardial glycogen deposition. Patients with PRKAG2 syndrome can develop cardiac hypertrophy, ventricular pre-excitation, supraventricular arrhythmias and conduction system disease, all of which increase the risk of sudden cardiac death. Some patients develop progressive heart failure necessitating heart transplantation. Current treatments include standard medications for heart failure and pacemaker/ICD implantation for arrhythmias. However, there is a significant need to treat the underlying causes of PRKAG2 syndrome. Small interfering RNA (siRNA) oligonucleotides present a promising therapeutic approach by reducing mutant PRKAG2 mRNA levels, thereby lowering AMPK activity. Hypothesis: Antibody oligonucleotide conjugates (AOCs) can be designed to target PRKAG2 mRNA to treat PRKAG2 syndrome. Aims: To investigate the tolerability and efficacy of an AOC targeting PRKAG2 mRNA in mice and non-human primates (NHPs). Methods: iPSC-derived cardiomyocytes were used to screen and identify a potent siRNA against PRKAG2 . The lead siRNA was conjugated to an anti-TfR1 monoclonal antibody to create AOC 1072 for targeted cardiac delivery and was subsequently administered to mice and NHPs. Results: In vitro screening identified an siRNA with an EC50 &lt;10 pM and a maximum PRKAG2 mRNA reduction &gt;90%. A single, IV injection of the mouse surrogate of AOC 1072 at 1 mg/kg (siRNA component) resulted in a potent and durable myocardial Prkag2 mRNA reduction in mice, with about 75% and 50% reduction observed at 2 and 6 months, respectively. AOC treatment reduced glycogen accumulation in the skeletal muscle of mice expressing the Prkag2 -R528G disease variant. A single IV administration of AOC 1072 at 3 mg/kg (siRNA component) resulted in about 85% reduction of cardiac PRKAG2 mRNA in NHPs at 28 days, with no adverse effects (ECG or heart weight). Conclusions: Our data suggests AOC technology can be used efficiently to deliver siRNA to the heart. This precision cardiology treatment can significantly reduce PRKAG2 mRNA expression, offering a promising therapeutic approach for PRKAG2 syndrome, a currently incurable genetic condition with very limited treatment options.
Abstract 4143962: Lineage-specific iPSC derived smooth muscle cells predict mannose receptor C type 2 deficiency accelerates aortic root enlargement in Marfan syndrome mice via exacerbating collagen deposition
Authors: Sho Kusadokoro, Nobu Yokoyama, Jennifer Kim, Nikhita Bolar, Alex Dalal, Albert Pedroza, Casey Gilles, Anna Marie Puaala, Avani Klinder, Atsushi Yamaguchi, Michael Fischbein
Journal: Circulation (2024)

Introduction: Marfan Syndrome (MFS) is a genetic disorder characterized by aortic root aneurysm formation, with risk of dissection and rupture. Proteomic profiling on human Marfan iPSC-derived second heart field (SHF) SMCs revealed decreased Mannose Receptor 2 (MRC2) expression. Given MRC2's role in collagen homeostasis, its reduction is hypothesized to impair collagen turnover and compromise aortic wall integrity, worsening TAA development in MFS. Methods: In vitro assays were performed on iPSC-derived SMCs from the SHF and cardiac neural crest (cNC) from MFS patients and control. MRC2's impact on collagen dynamics was assessed via western blot following targeted MRC2 knockdown and overexpression using lenti-vector. In vivo, MRC2 conditional SMC-specific knockout mice on WT and MFS backgrounds were generated to explore collagen turnover and its influence on MFS pathology and for single-cell RNA (scRNA) sequencing. Results: MRC2 expression was significantly lower and COL1a1 levels significantly higher in SHF-derived SMCs from MFS patients compared to cNC-derived and control SHF SMCs. MRC2 knockdown in these cells significantly increased COL1A1 expression, which normalized upon MRC2 overexpression. Longitudinal echocardiographic analysis of SMC-specific Marfan MRC2 KO mice showed significantly larger aortic root diameters at 24 weeks versus control (MFS-MRC2 KO vs. MFS and WT: 2.62±0.27 mm vs. 2.36±0.25 mm, p&lt;0.05 and 1.92±0.12, p&lt;0.05). Histological evaluation revealed increased adventitial collagen in the aortic root of MFS-MRC2 KO mice. scRNA showed MRC2 was primarily expressed in modulated SMCs (modSMCs) and that modSMCs in MFS SMC-specific MRC2 KO versus MFS control had upregulation of pathways involved in translation at the synapse/cytoplasm, ossification and osteoblast differentiation, and peptidase activity. Overall SMC and fibroblast gene expression profiles were similar when MRC2 was knocked out, however, the majority of gene expression appeared to be influenced by the MFS mutation itself. Conclusion: The study highlights that MRC2 plays a crucial role in aortic wall collagen homeostasis, with its deficiency markedly exacerbating TAA progression in MFS mice.