tbuckley/cabot-search huggingface dataset:
Abstract 4141486: Site-Specific Transcriptomic Patterns and Cell Types Associated with Hypertension
Authors: Zachary Milstone, Jesse Moreira, Karan Smith, Adam Gower, Yuiry Alekseyev, Jason Cunha, Nathaniel Fisher, Joshua Lepson, Ashlee Lamason, Brian Tao, Christopher Williams, Emelia Benjamin, Daniel Levy, Richard Mitchell, Robert Padera, Seung Hoan Choi, Deepa Gopal, Nathan Tucker, Jessica Fetterman
Journal: Circulation (2024)

Introduction: The biology of early human hypertensive heart disease (HHD) is largely unexplored due to limited cardiac tissue access. Site-specific transcriptomics of human cardiac tissue before development of overt HHD offers a unique vantage to understand the biology of HHD in human cardiac tissue. Hypothesis: We hypothesize that transcriptomic signatures and cell subtype proportions differ in human heart tissue from HTN donors compared to normotensive (NTN) donors in a site-specific manner. Methods: We performed bulk RNA-seq on rRNA-depleted libraries from left (LV) and right (RV) mid-ventricular-wall tissue (average depth 114 million reads/sample) collected postmortem from HTN (n=3, 67% Black/Latinx) and NTN (n=2, 50% Black/Latinx) donors. We performed single-nucleus RNA-seq (snRNA-Seq) on cardiac tissue from the same donors (average of 4,062 LV nuclei). Differential gene expression, lineage identification, and Gene Set Enrichment Analysis (GSEA) were performed with publicly available software. Results: All donors were female with matched postmortem intervals (time from death to tissue preservation; HTN 19±9 hours, NTN 18±6 hours). HTN donors were older (65±7 years) than NTN donors (36±16 years). A total of 416 genes were associated with HTN (Wald test, FDR q &lt;0.05) across both ventricles (correcting for site). When tested separately, 72 (LV) or 83 (RV) genes were associated with HTN (FDR q &lt;0.05), with 13 common genes, indicating site-specific differences. GSEA of genes ranked by Wald statistic computed across both ventricles showed that transcripts involved in single-stranded DNA helicase activity, branched-chain amino acid catabolism, and NAD-dependent deacetylase activity were coordinately associated with HTN (FDR q &lt;0.05). snRNA-seq revealed 9 cell types in these samples, including immune cells and chamber-specific cardiomyocytes (CMs) with higher proportions of LV CMs and lymphocytes associated with HTN compared to NTN. MYH6 and MYL7 expression was unchanged with respect to HTN by RNA-seq but lower in LV HTN CMs compared to NTN by snRNA-seq, suggesting dysregulation of contractile programming in HTN LV CMs. Conclusion: HTN is associated with altered cardiomyocyte/lymphocyte ratios, and site-specific differential expression of cardiac contractile elements. Further study is required to validate these findings with additional samples and elucidate mechanisms driving transcriptional program differences in the hypertensive human heart.
Abstract 4145828: The Interplay Between Exercise Load, Myocardial fibrosis, Ventricular Systolic Dysfunction and Ventricular Arrhythmias
Authors: Jarne De Paepe, Paolo D'Ambrosio, Ruben De Bosscher, Rik Pauwels, Christophe Dausin, Youri Bekhuis, Kristel Janssens, Jan Bogaert, Adrian Elliott, Olivier Ghekiere, Caroline Van De Heyning, Prashanthan Sanders, Jonathan Kalman, Diane Fatkin, Lieven Herbots, Rik Willems, Tomas Robyns, Hein Heidbuchel, Andre La Gerche, Guido Claessen
Journal: Circulation (2024)

Background: An increased prevalence of myocardial ventricular fibrosis, ventricular dysfunction and arrhythmias has been reported amongst highly trained endurance athletes, but trials investigating these adverse phenotypes in adequately sized and accurately phenotyped cohorts are largely lacking. We aimed to define the prevalence of ventricular fibrosis, ventricular systolic dysfunction, arrhythmia and their interplay in healthy endurance athletes. Methods: We analysed a male cohort of 244 young elite endurance athletes (20yr), 134 middle-aged recreational athletes (56yr) and 65 middle-aged non-athletic controls (55yr). CMR assessed for non-hinge point and hinge point late gadolinium enhancement (NH-LGE and H-LGE) and LVEF and RVEF. 24-hour Holter was performed to assess ventricular arrhythmia. Complex arrhythmia was defined as couplets, triplets and NSVT. Exercise load was based on questionnaires. Multiple logistic regression assessed the relationship between exercise load, LGE, ventricular systolic dysfunction and ventricular arrhythmia. Results: Middle-aged athletes had more NH-LGE (19.4% vs 9.2% vs 4.5%, p&lt;0.001) and H-LGE (29.9% vs 13.8% vs 15.6%, p=0.002) than middle-aged controls and young athletes respectively. Lifetime hours of endurance exercise and age increased the odds of NH-LGE (OR 1.034, 95% CI 1.001-1.069, p=0.044 and OR 1.032, 95% CI 1.006-1.058, p=0.014). A LVEF&lt;50% and/or RVEF&lt;45% was more prevalent in middle-aged and young athletes compared to controls (23.1% % vs 20.5% vs 7.7%, p=0.029). A higher lifetime training load increased the odds of RVEF&lt;45% (OR 1.059, 95% CI 1.014-1.105, p=0.009). LGE did not predict LVEF&gt;50% or RVEF&lt;45%. Both complex arrhythmia and a burden of &gt;0.1% VPB were more prevalent in middle-aged athletes compared to young athletes but not compared to controls (26.1% vs 9.8% vs 12.3%, p&lt;0.001 and 13.6% vs 4.9% vs 7.7%, p=0.012 respectively). NH-LGE and RVEF&lt;45% increased the odds of VPB burden &gt;0.1%. (OR 3.845, 95% CI 1.465-10.089, p=0.006 and OR 5.230, 95% CI 1.698-16.106, p=0.004 respectively). Conclusion: NH-LGE is associated with exercise load and more prevalent in middle-aged athletes compared to younger athletes and age-matched controls. When present, LGE is not associated with a reduced ventricular function. On the other hand, NH-LGE and reduced RVEF are risk factors for increased ventricular ectopic burden and middle-aged athletes show significantly more complex arrhythmia compared to younger athletes.
Abstract 4120515: Impact of 2022 AHA/ACC/HFSA Heart Failure Guideline Value Statement Publication on Medicare Drug Coverage Policies
Authors: Amrita Mukhopadhyay, Nathalia Ladino, Tyrel Stokes, Samrachana Adhikari, Aparna Narendrula, Stuart Katz, Harmony Reynolds, Allison Squires, Saul Blecker
Journal: Circulation (2024)

Background: Patients with heart failure (HF) often have difficulty obtaining life-saving medications due to coverage barriers, such as prior authorizations (PA) and high out of pocket (OOP) costs. To promote better insurance coverage of high value therapies, the AHA/ACC/HFSA added Value Statements to HF guidelines to inform policymakers about medication cost effectiveness. We assessed whether these guidelines influenced Medicare drug coverage policies for two life-saving, costly HF medications: angiotensin receptor neprilysin inhibitors (ARNI – guideline “high value”) and sodium glucose cotransporter 2 inhibitors (SGLT2i – guideline “intermediate value”). Methods: We performed an observational study of Medicare drug plans from 4/2020-4/2023 to assess for changes in ARNI and SGLT2i coverage after Value Statement publication (4/2022), and subsequent Medicare plan online update (10/2022). The primary outcome was any barrier to drug coverage (PA, tier ≥ 3 OOP cost-sharing, step therapy, or no coverage). Analysis utilized interrupted time series and difference-in-difference (DiD) approaches. DiD analyses used direct oral anticoagulants as a control due to similar cost and utilization as ARNI and SGLT2i, but with no Value Statement. Results: Among 7,396 Medicare drug plans, 94.3%-97.4% had coverage barriers to ARNI and 93.2%-96.6% to SGLT2i. The majority of barriers were due to tier ≥ 3 OOP cost-sharing requirements (ARNI: 94.3%-95.8%; SGLT2i: 93.2%-95.6%). Coverage barriers remained stable in 4/2022, and declined slightly in 10/2022 (Figure). In DiD analyses, the presence of a Value Statement was associated with a ~1 percentage point decline in coverage barriers for ARNI and SGLT2i. Conclusion: Coverage barriers to ARNI and SGLT2i were common and did not change much in response to Value Statements in HF Guidelines. Increased consideration for Value Statements by Medicare policy-makers is needed to meaningfully improve access to high value therapies.
Abstract 4139179: Is Prenatal Diagnosis Responsible for Differences in Timing to Postnatal Intervention for Critical Congenital Heart Defects?
Authors: Joyce Woo, Nina Gotteiner, Brett Anderson, Lynn Yee, William Grobman, Matthew Davis, Christina Laternser
Journal: Circulation (2024)

Introduction: The relationships between prenatal diagnosis of congenital heart defects (CHDs) and outcomes are inconsistent. Some studies have shown that compared to postnatal diagnosis, prenatal diagnosis is associated with later surgical timing and worse outcomes. These findings could be due to confounding because more severe CHDs are likelier to be diagnosed on prenatal ultrasonography. To bypass this confounding, we evaluated prenatal diagnosis as a mediator. Aim: To evaluate whether prenatal diagnosis of CHD mediates the association between disease severity and timing to postnatal intervention. Hypothesis: Infants with severe CHD receive intervention sooner than those with mild CHD due to a higher prenatal diagnosis prevalence. Methods: This is a retrospective cohort study of all infants who received their initial cardiac catheterization or surgery between 0-60 days (i.e., critical CHD) at Ann&amp;Robert H. Lurie Children’s Hospital of Chicago (2015-2021). Birthing individuals with inadequate prenatal care were excluded. The primary exposure variable was a three-level categorical variable derived from existing literature, categorizing disease severity based on anatomic factors (mild, moderate, and severe CHD). The outcome was age at intervention, i.e., cardiac catheterization or surgery, whichever occurred sooner, in days. The mediator variable was whether prenatal diagnosis occurred. Control variables included birth weight, sex, surgery during the COVID-19 pandemic, race, ethnicity, birth hospital’s level of perinatal care as designated by Illinois state, presence of a syndrome or non-cardiac abnormality, and insurance status. Results: In total, 429 parent-infant pairs met inclusion criteria; 68.3% had prenatal diagnosis and 28.4% had severe CHD. In adjusted analyses, compared to those with the mild CHD, those with moderate CHD had 40.0% higher probability of prenatal diagnosis (p&lt;0.001) and on average, received intervention 14 days sooner (p=0.001). Those with severe CHD had a 59.5% higher probability of prenatal diagnosis (p&lt;0.001), and on average received intervention 19 days sooner (p&lt;0.001). In a mediation analysis, prenatal diagnosis accounted for 27.2% of the difference in surgical timing between moderate and mild disease, and 29.5% of the difference in surgical timing between severe and mild disease ( Figure 1 ). Conclusion: The relationship between CHD severity and timing to postnatal intervention is partly attributable to prenatal diagnosis.
Abstract 4136983: Estimating Atrial Fibrillation Rate in Patients Using Artificial Intelligence Referenced to Tissue Action Potentials
Authors: Ricardo Carlos Abad Juan, Suhaas Anbazhakan, Samuel Ruiperez-Campillo, Miguel Rodrigo, Sanjiv Narayan
Journal: Circulation (2024)

Background: Ablation by pulmonary vein isolation (PVI) is the most effective approach to treat atrial fibrillation (AF), but 30-40% of patients may not respond. Studies including the CAPLA trial suggest that ablating sites of rapid activation on the posterior left atrial wall or elsewhere may improve success. However, AF rate is rarely calibrated and, since electrograms often include noise or far field activity, may overestimate rate (underestimate cycle length) at many sites. Hypothesis: We hypothesized that artificial intelligence (AI) algorithms may more accurately indicate local AF rate, by excluding spurious activations referenced to simultaneous monophasic action potential (MAP) recordings, compared to conventional measurements. Methods: We studied N=303 AF patients at ablation (68.2±8.0 years, 17.8% females, 72.9% non-paroxysmal AF). Patients were matched N=229 into development and one quarter (N=74) into hold-out test cohorts. Patients underwent AF mapping using multipolar catheters, and a subset with MAP catheters (MedFact, GmbH). We used the development set to train an AI algorithm to reliably detect AF activations, which we compared in the test cohort to a standard dV/dt approach referenced to adjacent MAPs within 2 mm (N=20 patients) and manually annotated activations (N=64 patients). Results: Fig A shows AF in a 66 year old woman, where dV/dt often marked non-physiological activations within repolarization shown in the adjacent MAP. Conversely, the AI system excluded spurious deflections and better correlated with experts (black). In summary, Fig. B shows that AI provided a higher F1 score than dV/dt compared to MAPs (median[IQR]: 0.86 [0.5 - 1] vs. 0.67 [0.40 - 0.73], p&lt;0.01) and experts (0.89 [0.73 - 1] vs. 0.72 [0.60 - 0.89]], p&lt;0.01). Fig C shows that the AI approach better identified AF cycle length (rate; blue) than standard approaches (green) that substantially underestimate cycle length (p&lt;0.05). Conclusions: In this large registry, a novel AI-based approach more accurately detected AF rates in clinical electrograms, referenced to experts and action potential recordings, than standard approaches which overestimated rate. AI may improve characterization of AF activity within the atria.
Abstract 4144559: Sex Differences in Vascular Remodeling in Pulmonary Hypertension are mediated by Endothelin-2
Authors: Lejla Medzikovic, Christine Cunningham, min li, Laila Aryan, Wasila Sun, ateyeh Dehghanitafti, Gregoire Ruffenach, Jason Hong, Mansoureh Eghbali
Journal: Circulation (2024)

Pulmonary arterial hypertension (PAH) is characterized by pulmonary arterial vascular remodelingleading to increased pulmonary artery pressure causing right ventricular hypertrophy, failure anddeath. The incidence of PAH is much higher in female patients, indicating that males may have aprotective factor that could help elucidate the pathogenesis of PAH. We have recently demonstratedthat the Y chromosome gene UTY protects against PH development in mice, however the fulldownstream mechanisms remains unknown. By integrating RNA-Seq on whole lung tissues fromUty-KO and WT male mice with a publically available male and female PAH lung microarraydataset, we found increased expression of Endothelin 2 (ET-2) in the lungs of Uty-KO compared toWT mice with PH as well as in the lungs of female patients compared to males with PAH. The roleof ET-1 is known in PAH, and Endothelin receptor antagonists are a common PAH therapy to whichfemale patients are more responsive. However, ET-2 has yet to be investigated in this context. Wevalidated that ET-2 expression is significantly increased in lung tissue from PAH female patientscompared to males. Plasma ET-2 concentration is also significantly higher in PAH patients versuscontrols. Interestingly, plasma ET-2 negatively correlates with pulmonary vascular resistance (PVR)and mean pulmonary arterial pressure (mPAP) in male PAH patients, whereas plasma ET-2significantly positively correlates with PVR and mPAP in female PAH patients. Functionally, wefound that recombinant ET-2 significantly inhibits proliferation of male pulmonary artery endothelialcells (PAECs), but significantly promotes proliferation in female PAECs. Similarly, ET-2 significantlyincreased proliferation of female pulmonary artery smooth muscle cells (PASMC), but not malePASMC. Together, we show that increased ET-2 expression may contribute to worsening PH bypromoting vascular remodeling in the lung and that elevated ET2 in females may at least partiallyexplain the higher incidence of female PAH patients
Abstract 4120573: Abrupt cardiac rupture of the patient with ATTR amyloidosis
Authors: Kento Tagata, Nomoto Yutaro, Koji Tao, Tetsuro Kataoka, Mitsuru Ohishi
Journal: Circulation (2024)

A Japanese male in his 80s was admitted to our emergency department with chest pain. His prior history was syncope and ventricular tachycardia. Transthoracic echocardiography (TTE) revealed thickening of the basal part of the antero-septal wall and thinning of the basal part of the inferior wall. Coronary angiography (CAG), cardiac MRI and blood test revealed no specific abnormalities. The day before his emergency admission, he visited the cardiology outpatient department for a periodic examination of cardiac hypertrophy. ECG, chest X-ray, and TTE were unchanged from his prior examination. However, that night, he experienced chest pain and was transferred to our hospital. On arrival, his vital signs were critical, with a blood pressure of 70/59 mmHg. ECG indicated ST elevation in antero-lateral leads. TTE detected pericardial effusion, and contrast-enhanced CT identified two focal areas of non-enhancement in the myocardium and pericardial effusion without signs of aortic dissection. CAG revealed no significant stenosis or obstructive lesion. During coronary angiography, the patient deteriorated to asystole. Cardiopulmonary resuscitation and percutaneous pericardial drainage were initiated. Hemorrhagic pericardial effusion was aspirated. Immediate surgical hemostasis was undergone, revealing about 2 cm lacerations and hematoma in the anterior and inferior wall. After surgery, he complained of abdominal discomfort. Esophageal gastrointestinal endoscopy was undergone to investigate the abdominal discomfort, and he was diagnosed with early gastric cancer. Endoscopic submucosal dissection (ESD) was undergone, and histopathological examination revealed adenocarcinoma and eosinophilic amorphous materials deposited in the submucosal vessels. Congo red staining of the submucosal vessels revealed orange-red areas. A technetium-99m pyrophosphatase scintigraphy showed Grade 2 uptake in the heart. Transthyretin (TTR) staining was positive in the specimen from ESD, leading to a diagnosis of TTR amyloidosis. Genetic test for TTR was negative, which led to a diagnosis of wild-type TTR amyloidosis and tafamidis was started. In cases of acute pericardial effusion and/or cardiac rupture, it is imperative to consider cardiac amyloidosis as a potential etiology, in addition to myocardial infarction and aortic dissection, especially in patients with left ventricular wall thickening, neuropathy, or abnormal ECG, also known as “red flag”.
Abstract 4123653: Association of Inflammatory Bowel Disease with the Risk of Atrial Fibrillation: A Meta-Analysis
Authors: Aman Goyal, GAURANGA MAHALWAR, Hritvik Jain, Sai Gautham Kanagala, John Locke
Journal: Circulation (2024)

Background: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a prevalent condition associated with chronic noninfectious inflammation of the gastrointestinal tract. It has been hypothesized that chronic inflammation can predispose patients to atrial fibrillation (AF), with proposed mechanisms being structural remodeling of atrial tissue, autonomic dysfunction, and oxidative stress; however, no clear evidence exists to support this. Aims: Our meta-analysis aims to pool all existing data to determine if there is an increased risk of AF in patients with IBD, providing more robust evidence on the matter. Methods: A systematic literature search was conducted using major databases (PubMed, EMBASE, and SCOPUS) aimed at studies focusing on AF development in patients with IBD. Further subgroup analyses were performed for ulcerative colitis (UC) and crohn’s disease (CD). Risk ratios (RR) with their corresponding 95% confidence intervals (CI) were pooled using a random-effects model in the Review Manager Software. Statistical significance was set at p &lt; 0.05. Results: Seven studies with 88,893,407 patients were included (1,002,719 and 87, 890, 688 patients in the IBD and non-IBD groups, respectively). IBD patients were at an increased risk of developing AF [RR: 1.52; 95% CI: 1.19-1.95; p=0.0009] compared to the non-IBD group. In subgroup analyses, patients with UC were at an increased risk of developing AF [RR: 1.29; 95% CI: 1.08-1.53; p=0.004], as were CD patients [RR: 1.30; 95% CI: 1.07-1.58; p=0.008] compared to the non-UC and non-CD groups, respectively (Figure 1). Conclusion: Patients with IBD are at nearly 1.5 times the risk of developing AF compared to the non-IBD population. Our meta-analysis was limited by heterogeneity among the studies, highlighting the importance of further large-scale prospective studies to establish more robust evidence and determine the real-world clinical significance of our findings. Furthermore, future research should explore the impact of confounding variables such as disease severity, medication usage, and lifestyle factors on the observed association between IBD and AF.
Abstract 4141480: Gender differences in bifurcation percutaneous coronary interventions: Update from the Prospective Global Registry for the Study of Bifurcation Lesion Interventions (PROGRESS-BIFURCATION)
Authors: Michaella Alexandrou, Dimitrios Strepkos, Athanasios Rempakos, Deniz Mutlu, Pedro Carvalho, Oleg Krestyaninov, Dmitrii Khelimskii, Barkin Kultursay, ali karagoz, Ufuk Yildirim, korhan soylu, Mahmut Uluganyan, Olga Mastrodemos, Bavana Rangan, Sandeep Jalli, Ahmed Al-Ogaili, Konstantinos Voudris, Yader Sandoval, M Nicholas Burke, Emmanouil Brilakis
Journal: Circulation (2024)

Background: Gender differences on short and long-term outcomes following bifurcation percutaneous coronary intervention (PCI) have received limited study. Research Questions: To examine gender differences in outcomes of bifurcation PCI. Methods: We examined the angiographic, procedural characteristics, and outcomes of 1084 bifurcation PCIs (1076 patients) performed at five centers between 2013-2024 from the Prospective Global Registry for the Study of Bifurcation Lesion Interventions (PROGRESS-BIFURCATION). Results: Women represented 25.19% of the entire study population. They were older (68.37±12.34 vs 66.09±11.54; p=0.001), less likely to be currently smokers (13.7% vs 20.4%; p=0.014), with higher left ventricular ejection fraction (%) (55.46±13.27 vs 53.16±12.55; p&lt;0.001) and lower baseline creatinine (0.85 vs 1.00; p&lt;0.001). Lesion characteristics were mostly similar, with slightly lower proximal and distal main vessel diameter in women. Their proximal main vessel was more likely to be left anterior descending artery (46.5% vs 39.4%; p=0.030) and less likely to be right coronary artery (10.3% vs 16.1%; p=0.030), compared to men. Technical success was similar (94.5% vs 94.6%; p=0.952), while procedural success was lower (89.6% vs 94.1%; p=0.011). In-hospital major adverse cardiac events (MACE) were more common in women (8.5% vs 4.2%; p=0.007), which presented with increased in-hospital mortality (4.1% vs 0.6%; p&lt;0.001), stroke (1.8% vs 0.1%; p=0.005) and bleeding (1.8% vs 0.2%; p=0.013). Their PCIs required equal procedure time, but lower fluoroscopy time, contrast volume and air kerma radiation dose. Female gender was independently associated with higher in-hospital major adverse cardiac events (MACE) (odds ratio (OR) 2.21; 95%CI 1.23-3.95; p=0.008) and lower procedural success (OR 0.56; 95%CI 0.32-1.00; p=0.044). Follow-up data were available for 733 patients (68.12%). The incidence of follow-up MACE was significantly higher in women (hazard ratio (HR) 1.36; 95%CI 1.02-1.81; p=0.038), while on adjusted mixed Cox proportional hazards analysis female gender was associated with higher follow-up MACE (HR 1.58; 95%CI 1.08-2.30; p=0.018). The incidence of follow-up mortality was similar between genders (HR 1.17; 95%CI 0.78-1.77; p=0.45). Conclusions: Bifurcation PCI can be accomplished with high technical success in women, but higher in-hospital and follow-up MACE, compared to men.