tbuckley/cabot-search huggingface dataset:
Abstract 4117883: Long noncoding RNAs and machine learning to improve cardiovascular outcomes of COVID-19
Authors: Kanita Karaduzovic-Hadziabdic, Muhamed Adilović, Lu Zhang, Andrew Lumley, Pranay Shah, Muhammad Shoaib, Venkata Satagopam, Prashant Srivastava, Costanza Emanueli, Simona Greco, Teresa Padro, Pedro Domingo, Mitja Lustrek, Markus Scholz, Maciej Rosolowski, Marko Jordan, Bettina Benczik, Bence Agg, Peter Ferdinandy, Andrew Baker, Guy Fagherazzi, Markus Ollert, Joanna Michel, Gabriel Sanchez, Hueseyin Firat, Timo Brandenburger, Fabio Martelli, Lina Badimon, Yvan Devaux
Journal: Circulation (2024)

Introduction/Background: Cardiovascular symptoms appear in a high proportion of patients in the few months following a severe SARS-CoV-2 infection. Non-invasive methods to predict disease severity could help personalizing healthcare and reducing the occurrence of these symptoms. Research Questions/Hypothesis: We hypothesized that blood long noncoding RNAs (lncRNAs) and machine learning (ML) could help predict COVID-19 severity. Goals/Aims: To develop a model based on lncRNAs and ML for predicting COVID-19 severity. Methods/Approach: Expression data of 2906 lncRNAs were obtained by targeted sequencing in plasma samples collected at baseline from four independent cohorts, totaling 564 COVID-19 patients. Patients were aged 18+ and were recruited from 2020 to 2023 in the PrediCOVID cohort (n=162; Luxembourg), the COVID19_OMICS-COVIRNA cohort (n=100, Italy), the TOCOVID cohort (n=233, Spain), and the MiRCOVID cohort (n=69, Germany). The study complied with the Declaration of Helsinki. Cohorts were approved by ethics committees and patients signed an informed consent. Results/Data: After data curation and pre-processing, 463 complete datasets were included in further analysis, representing 101 severe patients (in-hospital death or ICU admission) and 362 stable patients (no hospital admission or hospital admission but not ICU). Feature selection with Boruta, a random forest-based method, identified age and five lncRNAs (LINC01088-201, FGDP-AS1, LINC01088-209, AKAP13, and a novel lncRNA) associated with disease severity, which were used to build predictive models using six ML algorithms. A naïve Bayes model based on age and five lncRNAs predicted disease severity with an AUC of 0.875 [0.868-0.881] and an accuracy of 0.783 [0.775-0.791]. Conclusion: We developed a ML model including age and five lncRNAs predicting COVID-19 severity. This model could help improve patients’ management and cardiovascular outcomes.
Abstract 4118444: Right Ventricular Contractile Reserve and Right Ventricular-Pulmonary Arterial Coupling Are Impaired in Long-Term Survivors of Childhood Cancers
Authors: Chung Sum Samuel Ho, Julia Z. Shi, Daniel KL Cheuk, Frankie WT Cheng, Wilfred HS Wong, Yuk-ting Chan, Yiu-Fai Cheung
Journal: Circulation (2024)

Background: Childhood cancer survivors are at risk of right ventricular (RV) dysfunction in relation to cardiac toxicity due to chemotherapy and radiation therapy. This study tested the hypothesis that RV contractile reserve and RV-pulmonary arterial (PA) coupling are altered in long-term survivors of childhood cancers. Methods: Thirty survivors (60% men) aged 24.3 ± 5.2 years at 15.3 ± 6.3 years after completion of chemotherapy and thirty healthy control subjects (47% men) were studied. Resting and submaximal supine bicycle stress echocardiography was performed for assessment of RV fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), left ventricular (LV) and RV longitudinal strain, mitral and tricuspid annular velocities and myocardial acceleration during isovolumic contraction (IVA). The slope of the RV force-frequency relationship was derived from the change in IVA with the change in heart rate during exercise (△IVA/△heart rate), while RV-PA coupling was determined by the ratio between TAPSE and pulmonary arterial acceleration time indexed to RV ejection time (PAATi). Results: At rest, tricuspid annular systolic velocity and RV systolic strain were significantly lower in survivors ( P &lt; 0.05 for both), while RV FAC, TAPSE and IVA were similar between the two groups ( P &gt; 0.05 for all). During submaximal exercise testing, all RV systolic functional indices were significantly lower in survivors than controls ( P &lt; 0.05 for all). The slope of the RV force-frequency relationship was significantly flatter in survivors compared to controls (0.038 ± 0.002 vs 0.059 ± 0.003 m/sec 2 beats/min, P &lt; 0.001). For RV-PA coupling, TAPSE/PAATi was similar between survivors and controls at baseline but became significantly lower in survivors during submaximal exercise ( P = 0.002). Conclusions: The RV contractile reserve and RV-PA coupling are impaired during exercise in long-term survivors of childhood cancers. Future studies aimed at determining the clinical and prognostic significance of these impairments are warranted.
Abstract 4117922: The Role of Combined Renin Angiotensin Aldosterone System Inhibitors (RAASi) Plus Beta Blocker Therapy For Cardiotoxicity Prevention In Patients Under Chemotherapy For Breast Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Mohammad Khan, James Choi, Amir Akbari, Hannah Hart, Justin Goodfarb, Francisco Romeo, Kiran Mahmood
Journal: Circulation (2024)

Introduction: Anti-neoplastic agents, including anthracyclines and trastuzumab, frequently employed in breast cancer treatment carry on considerable cardiotoxic effects impairing both cardiac chamber and cardiac fiber parameters leading to incident heart failure. In response to this challenging side effect, numerous randomized controlled trials (RCTs) have investigated the cardioprotective efficacy of RAASi and beta-blockers (BBs) in patients undergoing anthracycline and trastuzumab chemotherapy. We aim to perform an updated meta-analysis to elucidate the potential cardioprotective properties of these medications in patients undergoing chemotherapy for breast cancer. Methods: A comprehensive search of the literature was performed through April 2024 on PubMed, EMBASE and Clinicaltrials.gov. In total, data from 4 randomized studies were extracted and analyzed. The primary analysis was the effect of RAASi and BBs on LVEF as well as global longitudinal strain (GLS). Data were analyzed using a random-effects model to derive weighted mean differences (WMDs) and 95% confidence intervals for both LVEF and GLS. Data was analyzed using Review Manager 5.3 (RevMan 5.3) software. Results: In total, data from 248 patients (N = 124 on cardioprotection; N = 124 without cardioprotection) undergoing treatment with anti-neoplastic agents for breast cancer were included. At the end of treatment, patients undergoing cardioprotective therapy demonstrated improved LVEF preservation compared to the control group, (mean difference 2.14 [0.03, 4.25]; P=0.05; I2 = 79%). In addition, patients undergoing dual RAASi + BB therapy showed better GLS preservation compared to control group (mean difference –1.37 [-2.01, -0.72]; P &lt; 0.0001; I2 = 0%). Conclusion: In breast cancer patients undergoing anti-neoplastic regimens comprising anthracycline and trastuzumab, the concomitant administration of RAASi and BBs demonstrated better LVEF as well as GLS preservation upon completion of treatment over those without cardioprotective therapy. These findings shed light on the potential benefit derived from the synergistic effects of RAASi and BBs therapy in safeguarding both cardiac chamber and fiber functions amidst aggressive anti-cancer regimens, although further investigations still need to be conducted.
Abstract 4117927: Prevalence of Obstructive Sleep Apnea Among Consecutive Patients with Atrial Fibrillation Using WatchPAT Home Sleep Testing: A Prospective Cohort Study
Authors: Eric Mills, Michael Cassidy, KyungAh Im, Tamar Sofer, Thomas Tadros, Paul Zei, William Sauer, Jorge Romero, David Martin, Elliott Antman, Sogol Javaheri
Journal: Circulation (2024)

Background: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice and is associated with significant morbidity, mortality, and health system costs. Obstructive sleep apnea (OSA) is a highly prevalent condition affecting more than one third of the global adult population and, among patients with comorbid AF, contributes to poor AF related quality of life. However, the prevalence of undiagnosed OSA in the general AF population is unknown. Methods: In this pragmatic, phase IV prospective cohort study, we performed sleep testing on consecutively enrolled ambulatory AF patients for OSA using a cloud-based disposable home sleep test (the WatchPAT system). The primary outcome of our study was the prevalence of undiagnosed mild (5≤AHI&lt;15) or moderate/severe (AHI≥15) OSA in the general AF population. A prespecified power analysis supports 80% power to detect a &lt;5% difference in OSA prevalence compared to the general population (defined by AHI cut-offs of ≥5 or ≥15). Results: We performed sleep testing in 180 AF patients. Enrollment concluded early after a prespecified interim power analysis showed a larger than predicted difference of OSA prevalence between AF patients and the general population. Among the patients tested, 126 (70.4%) had paroxysmal AF, and 53 (29.6%) had persistent/long standing persistent AF. None had previous sleep testing. Our results show that the prevalence of OSA was 83.3% by AHI≥5 and 47.2% had moderate/severe OSA (AHI≥15). Patients with persistent or long standing persistent AF demonstrated even higher rates of OSA with 51 (96.3%) testing positive for OSA (AHI≥5) and 35 (64.2%) with moderate/severe OSA (AHI≥15). Conversely, standardized OSA screening instruments (Stop-BANG questionnaire or Epworth Sleepiness Scale) were poorly predictive of OSA in AF patients (AUC 0.66 and AUC 0.44, respectively). Conclusions: Undiagnosed OSA is highly prevalent in the general AF population. Our results demonstrate that OSA prevalence in AF patients exceeds that in the general population with a high degree of confidence. Widely used clinical prediction instruments cannot effectively be used to guide sleep testing decisions in AF patients. Our results suggest routine OSA testing should be performed in the comprehensive evaluation of all AF patients.
Abstract 4117657: Targeting GPR39 for Hypoxia-induced Pulmonary Hypertension in Mice
Authors: Carmen Methner, Lijuan Liu, Sanjiv Kaul
Journal: Circulation (2024)

Background: Primary pulmonary arterial hypertension (PAH) is a disease affecting young subjects. It has very poor prognosis and optimal treatment is not available. 15-hydroxyeicosatetraenoic acid (15-HETE), a potent vasoconstrictor, has been implicated in the pathogenesis of PAH. Elevated levels of 15-HETE have been shown to be associated with worse prognosis in patients with PAH. Oral ingestion of 15-HETE leads to development of PAH in rodents. We recently showed that 15-HETE is the endogenous agonist for the G-protein coupled receptor 39 (GPR39) present in vascular smooth muscle cells. Hypothesis: We, therefore, hypothesized that global deletion of GPR39 (knock-out [KO] mice) would protect from PAH by removing the receptor through which 15-HETE causes vasoconstriction. Methods: Accordingly, 13 wild-type (WT) and 16 KO mice were placed in a hypoxia chamber (10% O 2 ). Litter-mate controls (7 WT and 13 KO) were subjected to normoxia (room air, 21% O 2 ). At the end of 4 weeks heart rate as well as aortic and right ventricular (RV) pressures were measured (latter using micromanometer-tipped catheter), and the animals were then euthanized for measurement of RV wall thickness and RV size from which RV wall stress was calculated. Results: Heart rate and systolic blood pressure were not different between the 4 groups . WT hypoxic animals developed PAH with peak RV systolic pressures (RVSP) being significantly higher than normoxic WT and hypoxic WT and hypoxic KO mice. (Figure 1) Similar results were noted for RV end-diastolic pressure (Figure 2) and RV wall stress (Figure 3). Conclusions: By deleting GPR39, the target for 15-HETE, we were able to prevent hypoxia induced PAH and RV dysfunction. Pharmacological inhibition of GPR39 may open new frontiers in the treatment of PAH.
Abstract 4118342: Acoustic Analysis For The Detection Of Leaflet Thrombosis After Transcatheter Aortic Valve Replacement
Authors: Lior Lupu, Aviel Shetrit, Adi Kadosh, Galit Aviram, Yan Topilsky, Shmuel Banai, Ofer Havakuk
Journal: Circulation (2024)

Introduction: Following trans-catheter aortic valve replacement (TAVR), patients may develop aortic valve leaflet thrombosis, a condition associated with an increased risk of embolic events. Currently, the diagnosis of post-TAVR leaflet thrombosis is based on echocardiography surveillance or cardiac tomography (CCT) scan, both require specialized team and equipment, and may also expose the patients to radiation and contrast. Acoustic analysis is a non-invasive reproducible method, which incorporates the recording of cardiac sounds and analyzing them via machine learning algorithms. Here, we investigated the diagnostic abilities of acoustic analysis in the detection of post-TAVR leaflet thrombosis. Methods: Using an electronic stethoscope, heart sounds were prospectively recorded at 2 time points: 24-hours and 6-months post-TAVR. CCT scan was performed 6-months following TAVR to detect leaflet thrombosis. Acoustic sounds were analyzed, using a Gaussian support vector machine (SVM) algorithm, to identify features associated with leaflet thrombosis. Results: Of 19 consecutive patients, 3 were found to have high-grade leaflet thrombosis based on CCT results. The SVM algorithm effectively classified heart sounds into "normal" and "thrombotic", with a sensitivity of 100% and specificity of 97.2%. Following anticoagulation therapy, all 3 patients showed no signs of leaflet thrombosis on follow-up CCT scans and were also classified as "normal" by the algorithm. Notably, at the time of leaflet thrombosis, Doppler echocardiographies showed normal pressure gradients across the affected valves. Conclusions: These initial results suggest that acoustic analysis, combined with machine learning algorithms, may identify post-TAVR leaflet thrombosis, providing a non-invasive, cost-effective, and radiation-free alternative to traditional diagnostic methods.
Abstract 4119094: Claims-Based versus Registry-Reported Stroke Events in the NCDR Left Atrial Appendage Occlusion Registry
Authors: Kamil Faridi, James Freeman, Yongfei Wang, Lucy Pereira, Sarah Zimmerman, Daniel Friedman, Richa Sharma, Angela Higgins, Bobak Mortazavi, Joseph Ross, Harlan Krumholz, Robert Yeh, Jeptha Curtis
Journal: Circulation (2024)

Background: Administrative claims data are increasingly used for post-marketing surveillance of drugs and medical devices, though data reliability remains uncertain. Given their associated morbidity and mortality, stroke events are particularly important to monitor for cardiovascular therapies such as transcatheter left atrial appendage occlusion (LAAO). However, there are limited data comparing stroke events in contemporary claims data to events reported in large nationwide registries with comprehensive data collection. Aim: To compare stroke events in Medicare claims data with adjudicated registry-reported events in the National Cardiovascular Data Registry Left Atrial Appendage Occlusion (LAAO) Registry. Methods: LAAO Registry data were linked with 2016-2022 Medicare inpatient claims. Primary diagnosis ICD-10 codes from inpatient hospitalizations were compared to adjudicated registry-reported ischemic and hemorrhagic stroke events occurring after discharge with up to two years of follow-up. In multiple secondary analyses, primary and secondary diagnosis codes were counted as events in claims data and patients with prior history of stroke were also excluded. Results: The cohort included 71,043 adults ≥65 years old in the LAAO Registry with inpatient Medicare data. Following LAAO hospitalization discharge, there were 1405 claims-based and 1308 registry-reported total stroke events. Sensitivity and positive predictive value (PPV) of claims for identifying registry-reported events were 60.8% and 50.5% for ischemic stroke (kappa statistic 0.55), 42.7% and 50.5% for hemorrhagic stroke (kappa 0.46), and 58.1% and 54.1% for all stroke (kappa 0.55), respectively. Inclusion of secondary diagnosis codes improved sensitivity of claims (70.3% for ischemic stroke, 53.9% for hemorrhagic stroke and 67.0% for all stroke), but PPV decreased (44.8% for ischemic stroke, 34.8% for hemorrhagic stroke and 47.8% for all stroke). Specificity and negative predictive values of claims data were &gt;98% for all stroke types. Findings were similar after excluding patients with prior history of stroke ( Table ). Conclusions: Among Medicare patients in the LAAO Registry, administrative claims data had moderate agreement with adjudicated registry-reported stroke events. Claims data may not reliably capture all stroke events in real-world practice, and additional event ascertainment methods may be needed to ensure accurate assessment of stroke in post-marketing surveillance efforts.
Abstract 4115690: COL4A1-related Vascular Disease Displays Strikingly Different Penetrance, Onset, and Expressivity in Literature versus Biobank-Derived Cases
Authors: David Blair, Monica Penon-Portmann
Journal: Circulation (2024)

Monogenic cardiovascular diseases present throughout the human lifespan with varying symptoms. For most, our understanding of their penetrance, onset, and expressivity is derived from published case reports. The extent to which these literature-derived cases capture the full allelic and phenotypic spectrum is unknown, particularly since the literature is biased towards severe presentations. To illustrate, we investigated the penetrance (i.e. the presence of at least one symptom), onset, and phenotypic expressivity of a rare genetic disease linked to hemorrhagic stroke and other complications: COL4A1 -related vascular disease (COL4A1VD, or Gould Syndrome). We performed a systematic review of COL4A1VD cases reported in the biomedical literature ( N =459), normalizing their genetic variants and symptoms to controlled terminologies. We then investigated the phenotypic expression among COL4A1VD pathogenic variant carriers isolated from two population-scale biobanks (the UK Biobank and All of Us Research Program; combined N =714,246), identifying 178 subjects (prevalence: 0.025%) that should be at high risk for COL4A1VD-related symptoms. Based on the literature, the penetrance of COL4A1VD is approximately 92% (95% CI: 90%-95%), with each case expressing 4.3 symptoms on average. Neurologic complications were the most common finding, observed in 85% of symptomatic patients. Alternatively, the biobank-derived cohort displayed an overall enrichment for disease-related symptoms (COL4A1 pathogenic carriers are more likely to have increased symptom burden compared to non-carrier controls; P&lt;0.005), but the penetrance of the variants was substantially reduced (34%; 95% CI: 26%-41%). In addition, this cohort expressed fewer symptoms on average (0.8 per carrier), with renal complications being far more common (78% of symptomatic biobank patients vs 22% of literature-derived cases; P &lt; 0.001). Finally, the apparent age-of-onset was much later for the biobank-derived cohort (57-years vs 5-years for the literature cases). Most of these differences reflect the distinct ascertainment of these two COL4A1VD cohorts, but they also highlight our incomplete understanding of the true penetrance, expressivity, and onset for this rare disease. These results have important implications for COL4A1VD-related genetic counseling and surveillance, and they highlight a need for new methods that formally integrate the rare disease knowledge captured from these distinct data sources.
Abstract 4119078: Adjunctive pulmonary artery catheter for patients with cardiogenic shock treated with impella: a meta-analysis
Authors: Lucas Barbosa, Beatriz Araujo, Buena Aziri, Edin Begic
Journal: Circulation (2024)

Introduction: The efficacy and safety of use and impact of pulmonary artery catheter (PAC) in patients with cardiogenic shock (CS) treated with Impella remains unclear. The use of PAC in conjunction with Impella for patients with CS might be associated with improved clinical outcomes and increased safety compared to the use of Impella alone. We aimed to perform a systematic review and meta-analysis comparing Impella with versus without PAC for patients with CS. Methods: We systematically searched PubMed, Embase, and Cochrane databases for studies comparing PAC use in patients with CS treated with Impella. We pooled odds ratios (OR) with 95% confidence intervals (CI) applying random-effects model. We used R version 4.3.2 for statistical analyses. Results: We included two observational studies comprising 11,463 patients, of whom 6,058 (53%) had PAC. Compared with no PAC, the use of PAC was associated with a significantly lower in short-term mortality rates (37% vs. 42%; OR 0.83; 95% CI 0.77-0.90; p&lt;0.01; Figure 1A). There was no significant difference in the incidence of arrhythmias 59% vs. 63%; OR 1.14; 95% CI 0.92-1.41 p=0.44; Figure 1B) or renal complications between groups (47% vs. 50%; OR 1.08; 95% CI 1.00-1.17; p=0.06; Figure 1C). Conclusions: In patients with CS, adjunctive PAC to Impella is associated with lower mortality rates, but no significant difference in arrhythmias and renal complications. Randomized controlled trials are warranted to further validate this results.