tbuckley/cabot-search huggingface dataset:
Abstract 4147295: Outcomes after Acute Thoracic Aortic Dissection in Children and Young Adults ≤30 years of age
Authors: Edward Jones, Angela Yetman, Siddharth Prakash, Alana Cecchi, Alan Braverman, Seda Tierney, Richmond Jeremy, Jeremy Steele, Nadia Espahbodi, Dianna Milewicz, Shaine MORRIS
Journal: Circulation (2024)

Background: Thoracic aortic dissection (TAD) is rare in patients under 30 years of age, and is associated with high morbidity and mortality. There is limited published data on factors impacting survival and long-term outcomes after TAD in younger patients. Objective: Genetic and clinical findings associated with TAD in patients aged 30 and younger were analyzed to identify predictors of long-term post-dissection outcomes. Methods: This retrospective cohort study included patients from the Collaborative for Longitudinal Aortic Research in the Young and the Montalcino Aortic Consortium. Any patient with a type A or type B TAD that occurred at the age of 30 or younger was included. Results: A total of 62 patients were included (53% male). Median age at first TAD was 23.9 years (IQR 18.0-27.0) with range of 3.0 to 30.8 years; 40 (65%) were type A and 22 (35%) were type B dissections. All patients carried a genetic diagnosis, as this is required for both registries, with the highest proportion carrying TGFBR2 or ACTA2 pathogenic variants (PVs, Figure 1A). Median post-TAD follow-up was 7.8 years (IQR 2.1-11.9). Overall survival was 85% [76-95%], 83% [74-93%], and 75% [64-88%] at 1, 5, and 10 years, respectively. Freedom from death or additional aortic event was 79% [69-90%], 72% [61-86%], and 55% [42-72%] at 1, 5, and 10 years and was lower for individuals with TGFβ pathway ( SMAD3 , TGFB2 , TGFBR1 , TGFBR2 ) PVs compared to PVs in smooth muscle ( ACTA2 , MYLK , PRKG1 ) or extracellular matrix genes ( COL3A1 , FBN1 ) (p=0.12) (Figure 1B). In univariable Cox regression analysis, only aortic rupture at the time of initial TAD (HR 3.0 [1.2-7.6], p=0.018) and type A dissection (HR 3.9 [1.1-13.2], p=0.029) were significant predictors of death or additional aortic event (Table 1). Conclusion: TAD in young patients causes significant morbidity and mortality. Long-term outcomes may vary by dissection type, presence of aortic rupture, and mutated gene.
Abstract 4147580: Global and regional burden of alcohol-related hypertension from 1990 to 2021: An analysis of GBD study 2021
Authors: Malik Saad Hayat, Muhammad Talha Shaukat, Wania Rehman, Muhammad Shahzaib, Muhammad Imaz Bhatti, Aqeeb Ur Rehman, Aleenah Mohsin
Journal: Circulation (2024)

Background and Aims: Hypertension stands as the foremost preventable cause of premature mortality and is expected to have a global burden of up to 55%. Here we aim to examine the trends in age-standardized death rates (ASDR), years of life lost (YLL), and disability-adjusted life years (DALY) for alcoholic hypertension, pinpoint the vulnerable populations, and raise awareness about the global health burden of alcohol-related hypertension. Methods: Data on alcohol-related hypertension was extracted from the Global Burden of Diseases 2021 study, including ASDR, YLL, and DALY from 1990 to 2021. The dataset was globally divided and categorized by continents and World Bank income levels. Joinpoint regression was performed to determine annual percentage change (APC) and average annual percentage change (AAPC) from 1990 to 2021. Results: Globally, the age standardized death rates (ASDR) for alcohol-related hypertension had an overall decline from 1990-2021. In 1990, ASDR was 1.12 (95% UI 0.72-1.6) and it declined to 0.94 in 2021 (AAPC=-0.54; 95% CI -0.57 to -0.50). Although the overall trend is declining, some prominent spikes in mortality rate were observed, with the most prominent one seen from 2006-2010 (APC=1.38; 95% CI 1.04-1.82). Globally, the disability-adjusted life-years (DALYs) rate was 23.75 in 1990 and it decreased to 18.86 in 2021 (AAPC=-0.73; 95% CI -0.76 to -0.69). From 1990 to 2021, the age standardized years of life lost (YLL) showed a continuous drop with an AAPC of -0.78 (95% CI -0.81 to -0.75). In continent-wise analysis, North America and Europe had higher ASDRs while Asia and Africa had lower ASDRs. From 1990 to 2021, North America and Europe had AAPC of 0.44 (95% CI 0.36 to 0.53) and AAPC of 0.23 (95% CI 0.16 to 0.31) respectively. Conversely, the AAPCs for Africa and Asia showed significant decline and were -0.16 (95% CI -0.19 to -0.15) and -1.37 (95% CI -1.41 to -1.33) respectively. According to World Bank income levels, upper-middle income countries had declining death rates while lower-middle and lower-income countries had increasing death rates throughout. Conclusion: Alcohol-related hypertension remains a global health concern. While overall trends show a decline in mortality rates, spikes and variations across continents and income levels highlight the need for targeted interventions.
Abstract 4147561: Impact of Obstructive Sleep Apnea in Patients With Concomitant Heart Failure With Preserved Ejection Fraction; A Retrospective Population-Based Analysis
Authors: Gabriel Alugba, GODFREY TABOWEI, Oghenetejiri Gbegbaje, Oboseh Ogedegbe, Ovie Okorare, Boluwaduro Adeyemi, Folake Ishola, Oluwagbemiga Oyeleye, Favour Nelson, Endurance Evbayekha, Dipal Patel
Journal: Circulation (2024)

Introduction: Recent evidence from the literature has shown that obstructive sleep apnea (OSA) may contribute to worsening outcomes of patients with heart failure. However, most OSA studies were conducted in the HFrEF population. There remains scarce data on the impact of OSA in HFpEF hence, we aimed to study this population. Methods: We conducted a retrospective analysis of the 2020 National Inpatient Sample (NIS) database. Using the ICD-10 codes, we identified the codes for HFpEF and OSA. We adjusted for cofounders and used multivariate logistic regression model to analyze the odds ratio (adjusted odds ratio (aOR)) of our outcomes of interest. Result: There were 2,115,015 hospitalizations for HFpEF, and 18.1% (383,624) had a diagnosis of obstructive sleep apnea. The mean age was 69.5 years, with males having a prevalence of 51%. Of these, 74% were Caucasians, 17.26% were Blacks, and 5.24% were Hispanics. Following multivariate analysis, we found that HFpEF patients with OSA had significant odds of atrial fibrillation, adjusted odds ratio (aOR) 1.28(1.26 -1.31 p=0.000), coronary artery disease 1.23(1.20-1.26 p=0.000), obesity 3.49(3.41-3.57 p=0.000), diabetes mellitus 1.11(1.08-1.14 p=0.000), second-degree heart block 1.2(1.09-1.34 p=0.000), bifascicular heart block 1.08(1.02-1.14 p=0.003), defibrillator use 1.36 (1.04-1.77 p=0.026). However, OSA was not significantly associated with atrial flutter 1.03(0.99-1.06 p=0.13), third-degree heart block 1.07(0.99-1.15 p=0.072), ventricular tachycardia 1.01(0.95-1.07 p= 0.762). Conclusion: This analysis showed that HFpEF patients with OSA had higher likelihood of arrhythmias, and ischemic cardiac events. Lifestyle modifications including weight loss, healthy diet, and appropriate CPAP use should be encouraged in these patients.
Abstract 4147380: Cardiomyocyte Contractile Phenotype as a Marker of Cardiomyopathy Risk
Authors: Stuart Campbell, Yusuf Rasheed, Saiti Halder, Kaiquan Kenneth Ng, Samuel Young, Lynne Kim, Xia Li, Martina Brueckner, John Stendahl, Cassady Rupert
Journal: Circulation (2024)

Introduction: Cascade genetic screening for risk stratification is standard practice in the family of a patient diagnosed with hypertrophic cardiomyopathy (HCM), provided that a pathogenic mutation is present. We sought an alternative to genetic testing for cases where the patient lacks any suspicious variants (genotype-negative). Hypothesis: Induced pluripotent stem cell (iPSC)-derived cardiomyocytes from HCM patients with pathogenic mutations exhibit one or more altered contractile parameters when formed into engineered heart tissues (EHTs). These include elevated peak force, delayed relaxation, or blunted length-dependent activation (LDA). We hypothesized that EHTs derived from genotype-negative HCM patients would show similar contractile aberrations. If so, aberrant contractile phenotype could serve as a marker of HCM risk in screening family members when genetic testing is inconclusive. Methods: A total of 18 iPSC lines were obtained from a combination of public biobanks, institutional sources, and blood samples from consenting patients. These included lines from apparently healthy individuals (n=11) and from genotype-unknown or genotype-negative HCM patients (n=7). Four of the healthy lines were randomly selected as reference controls and the remaining 14 lines formed a blinded cohort. iPSCs were differentiated into cardiomyocytes and formed into EHTs using MyoPod tissue scaffolds. Following three weeks of culture, EHT contractility and LDA were assessed. Bootstrapping analysis was used to compare blinded EHT behavior against the reference group to mimic a diagnostic test. Results: None of the genotype-negative EHT groups showed statistically significant contractile differences compared to reference panels. One apparently healthy control EHT showed a significant (p&lt;0.05) increase in contractile force; exome sequencing revealed a rare FHOD3 mutation (D284N). Only one HCM patient line showed statistically significant change in contractility relative to reference (31% drop in normalized LDA, p&lt;0.05). Sequencing revealed a known pathogenic HCM mutation ( MYH7 K351E) in that patient. Conclusions: EHTs derived from genotype-negative HCM patients do not exhibit detectable alterations in contractile behavior, but patient EHTs harboring suspected or known pathogenic variants reliably do. This method has the potential to determine mutation penetrance in specific patients or pathogenicity of novel variants.
Abstract 4147094: Efficacy and Safety of Direct-Acting Oral Anticoagulants Compared to Vitamin K Antagonists for Atrial Fibrillation in Patients with Liver Cirrhosis: A Meta-Analysis
Authors: Maria Clara Ramos Miranda, Charles Karel Santos, Gabriel Barbosa, Thallys Nogueira, Antonio da Silva Menezes Junior
Journal: Circulation (2024)

Background: Direct-acting oral anticoagulants (DOACs) have emerged as a preferred alternative to Vitamin K Antagonists (VKAs) for patients with atrial fibrillation (AF). However, the exclusion of patients with liver cirrhosis (LC) from recent clinical trials leaves the efficacy and safety of DOACs in this population unclear. Hypothesis: DOACs are more effective and have a better safety profile compared to VKAs in patients with AF and LC. Methods: Following the PRISMA guidelines, we searched PubMed, Cochrane Library, Embase, Scopus, Web of Science, and CNKI databases for randomized clinical trials (RCTs) and observational studies comparing DOACs and VKAs in patients with AF and LC. Statistical analysis was performed using the metafor package in R software. Heterogeneity was assessed using the I2 statistic, and a random-effects model was employed to calculate pooled Hazard Ratios (HRs). For trivial heterogeneity (I2&lt;25%), a fixed-effect model was used. The confidence interval (CI) was set at 95%. Results: A total of one RCT and eight observational studies, encompassing 21903 patients, were included. Of these, 9882 patients were treated with DOACs and 11211 with VKAs. In 10105 patients with AF and LC, the incidence of major bleeding events was significantly lower in the DOAC group compared to the VKA group (HR 0.64; 95%CI 0.55-0.74; p&lt;0.001; I2=0%) (Figure 1A). The pooled adjusted effect estimates from multivariable analysis and inverse probability weighting for major bleeding were consistent (HR 0.71; 95%CI 0.61-0.82; p&lt;0.001; I2=7%) (Figure 1B). Additionally, the DOAC group exhibited lower rates of gastrointestinal (GI) bleeding (HR 0.76; 95%CI 0.69-0.85; p&lt;0.001; I2=18%) and intracranial hemorrhage (ICH) (HR 0.71; 95%CI 0.59-0.85; p&lt;0.001; I2=0%). There were no significant differences in thromboembolic events (Figure 2A) and all-cause mortality (Figure 2B) between the groups. Meta-regression analyses showed no significant impact of age, sex, follow-up duration, or baseline antiplatelet therapy on major bleeding events. Conclusion: In patients with AF and LC, DOACs are associated with a safer bleeding profile compared to VKAs, showing a reduced risk of major bleeding, GI bleeding, and ICH. However, no significant differences were observed in thromboembolic events or all-cause mortality. These findings suggest the potential of DOACs as a safer alternative in this patient population, warranting further validation through well-designed clinical studies.
Abstract 4148170: Impact of cancer on healthcare utilization in patients with heart failure
Authors: Don Mathew
Journal: Circulation (2024)

Background: Cardiovascular disease is an important cause for mortality in cancer patients and cancer is a primary cause of non- cardiac mortality in patients with heart failure. With an estimated 17 million cancer survivors in the US, with numbers only expected to increase and a projected 8 million heart failure patients by 2030, these diseases have a tremendous impact on healthcare costs. The aim of this study is to determine the hospital resource utilization in patients with heart failure and cancer. Methods: This is a retrospective cohort study using the Agency of Healthcare Research and Quality’s National Readmission Database (NRD) for the year 2019. Patients with a principal discharge diagnosis of heart failure were stratified into two groups based on presence of cancer. Weighting of patient level observations was implemented to obtain national level estimates. The primary outcome was 30-day all-cause hospital readmission. The secondary outcomes analyzed were 30- day mortality rate, mean length of stay and mean cost of hospitalization. The five most common causes of readmission were also determined. Results: 53, 219 weighted heart failure hospitalizations had cancer, while 996,566 did not have cancer. Patients with cancer had a significantly higher rate of 30-day readmission rate (25.6 % vs 22.1%; OR: 1.22; p &lt;0.05). Patients with cancer also had a higher 30-day mortality rate (5.7% vs 3.1%; OR: 1.6; p &lt;0.05), longer length of stay (6.14 vs 5.6 days; p &lt;0.05) and higher hospitalization costs ($ 15,191 vs $14,013; p &lt; 0.05). More than one third of readmissions were due to heart failure. Conclusion: Among patients with heart failure, a co-existing diagnosis of cancer is associated with increased 30-day readmission rate, increased 30-day mortality, longer length of stay and higher hospitalization costs.
Abstract 4147280: Combined BMP9 and BMP10 inhibition elicits Hereditary Hemorrhagic Telangiectasia (HHT)-like phenotypes in susceptible mice
Authors: Shreyas Rajesh, Gregory Gipson, Ana Zeghibe, Riley Brackin, John Lees-Shepherd, Sarah Hatsell, Aris Economides, Paul Yu
Journal: Circulation (2024)

Background: Pulmonary arterial hypertension (PAH) and hereditary hemorrhagic telangiectasia (HHT) are congenital vascular syndromes arising from mutations in a common set of genes of the bone morphogenetic protein (BMP) and TGFβ signaling pathway. Sotatercept, a novel therapy for PAH targeting activin signaling, is associated with telangiectasias and arteriovenous malformations (AVM), suggesting perturbation of BMP or activin signaling in PAH can lead to HHT mimicry. To identify the ligands responsible for HHT-mimicry, we tested a panel of molecules with different activities against BMP and activin ligands in HHT-prone mice for the ability to induce AVMs. Methods: Several recombinant proteins or antibodies with potential therapeutic effects in experimental or human pulmonary hypertension—anti-BMP9, anti-BMP10, ALK1-Fc (a BMP9/BMP10 ligand trap), ACTRIIA-Fc a.k.a. sotatercept (an activin/GDF/BMP10 and mild BMP9 ligand trap), ACTRIIB-Fc (an activin/GDF/BMP9/BMP10 ligand trap), or isotype control—were administered to HHT-prone 129X1/SvJ mice, at either 3- or 6-week of age for fifteen weeks (5-10 mg/kg twice weekly), with weekly paw and digital skin surveys, and blood counts taken at time of euthanasia. Results: Treatment with ACTRIIB-Fc or ALK1-Fc led to prominent hindlimb digital AVMs and bleeding at high frequency, while anti-BMP10 induced tail AVMs. AVMs occurred within 30 days when treatment was initiated at 3 weeks of age, and 60 days when initiated at 6 weeks of age. Treatment with ACTRIIB-Fc promoted weight gain, consistent with known anabolic effects of this ligand trap on muscle and bone. Conclusions: Combined antagonism of BMP9/BMP10 via ACTRIIB-Fc or ALK1-Fc exerted the strongest HHT mimicry in susceptible mice, while selective or weaker antagonism of BMP9 or BMP10 via neutralizing antibodies, ALK1-Fc, or ACTRIIA-Fc was less potent. HHT-susceptible strains of mice challenged with prospective PAH therapies can be used to reveal potential for HHT-mimicry due to BMP9/BMP10 antagonism in an age-dependent fashion. This pre-clinical model may be helpful to screen for the risk of AVMs in prospective therapies modulating BMP/activin signaling for PAH or other conditions.
Abstract 4147026: Predicting coronary artery disease using an exome-based estimate of KIV-2 repeat count in the Lp(a) gene
Authors: Natalie Telis, Hang Dai, Dana Wyman, Simon White, Basil Khuder, Francisco Tanudjaja, Nicole Washington, William Lee, Elizabeth Cirulli, Shishi Luo
Journal: Circulation (2024)

Introduction: Lipoprotein a (Lp(a)) levels are an often unmeasured predictor of future risk of cardiovascular disease. Unlike LDL, HDL, and triglycerides, Lp(a) levels are believed to be genetically determined; they are not altered by lipid-lowering medications or dietary changes, and are consistent over a lifetime, making them a potential early-life predictor of adult morbidity. However, genetic predictors of Lp(a) are challenging to design. Repeats of the kringle IV subtype 2 domain (KIV-2) contribute significantly but are extremely challenging to quantify via next-generation sequencing; this variability is particularly impactful in non-European ancestries. Methods: We analyzed ~110K individuals with paired clinical and exome sequencing data from six medical centers. We developed a coverage-based method to determine KIV-2 repeat counts. We validated that these counts associated with clinical Lp(a) measurements derived from the course of care (n = 2039 individuals). We calculated an expected Lp(a) in units of nmol/L using a genetic risk score (GRS) based on 43 variants in the Lp(a) gene. We identified instances of CAD via ICD9CM, ICD10CM and SNOMED terms present in the medical record. Results: Adding the number of KIV-2 repeats to the GRS substantially improved prediction of clinical Lp(a) measurements, for example improving the r-squared for non-Europeans five-fold (from 0.05 to 0.22). Individuals with fewer than 15 estimated KIV-2 repeats and a high GRS-predicted Lp(a) (high risk group) have a mean measured Lp(a) of that is 10-fold that of those in the lowest category of GRS-predicted Lp(a) (low risk group). In the full cohort, most of whom had not been measured for Lp(a), we find that relative to the low risk group, the high risk individuals are 1.6x more likely to have CAD. Conclusion: Lp(a) is a potentially useful biomarker with consistency over a lifetime and implications for future cardiovascular morbidity. We developed a method for estimating the number of KIV-2 repeats, a challenging component of genetic prediction of Lp(a). This estimate can be used in combination with a GRS to predict Lp(a), especially in individuals with non-European ancestry where GRS-based estimates fall short. The final prediction is associated with increased risk of CAD.
Abstract 4147587: Missed Opportunities To Optimize Lipid-lowering Therapy Following Revascularization In Patients With ASCVD
Authors: Hannah Ayers, Vicki Groo, Erika Hellenbart, Stephanie Dwyer Kaluzna, Ali Alaraj, David Tofovic, Melissa Duckett, Robert DiDomenico
Journal: Circulation (2024)

Introduction: Although attainment of LDL-C levels &lt; 70 mg/dl with lipid lowering therapy (LLT) is associated with decreased rates of ASCVD events, up to 58% of patients have LDL-C &gt; 70 mg/dL one year after coronary revascularization and &lt;50% have their LLT intensified. Research Questions: Following revascularization for ASCVD, how often do clinicians have the opportunity to obtain follow-up lipid profiles and intensify LLT? Goals: Evaluate the number of ambulatory care (AC) visits at which follow-up lipid profiles and/or LLT intensification failed to occur (e.g., missed opportunity) following revascularization in patients with ASCVD. Methods: We report a retrospective cohort study evaluating lipid management following revascularization for ASCVD of the coronary, cerebral, or peripheral arteries between July 2021 – July 2022. Patients were identified from procedure lists. Exclusion criteria included baseline LDL-C &lt; 70 mg/dl, triglycerides &gt; 500 mg/dl, dialysis dependence, and no follow-up care within 6 months of revascularization. The number of AC visits with a provider and LLT intensification following revascularization were compared between patients with a follow-up lipid panel versus those without within 15 months post-revascularization. Logistic regression was performed to identify characteristics associated with obtaining a follow-up lipid profile. Results: Of the 159 patients included, 69 (43%) had a follow-up lipid panel for evaluation at an average of 162±115 days after revascularization; 35 (22% of the entire cohort) achieved an LDL &lt;70 mg/dL. Patients with a follow-up lipid panel had significantly more AC visits and had higher rates of LLT intensification than those without follow-up lipids (Figure). Among the 90 patients without follow-up lipid profiles, there were a total of 363 missed opportunities to reassess lipids. Follow-up with either cardiology (OR 5.8 [95% CI 1.4-24.2]) or primary care (OR 4.1 [95% CI 1.8-9.3]) and diabetes (OR 2.7 [95% CI 1.2-5.9]) were positively associated with follow-up lipids; follow-up with vascular surgery (OR 0.2 [95% CI 0.0-0.9]), and heart failure (OR 0.2 [95% CI 0.1-0.8]) or CKD (OR 0.4 [95% CI 0.2-1.0]) were negatively associated with follow-up lipid panels. Conclusion: Post-revascularization care of high-risk ASCVD patients is suboptimal; we identified many missed opportunities to reassess lipids and intensify LLT.