tbuckley/cabot-search huggingface dataset:
Abstract 13015: First-degree Atrioventricular Block is Associated With Incident Atrial Fibrillation in the Japanese General Population Aged ≥ 40 Years
Authors: Yoshihiro Tanaka, Ravi B Patel, Hayato Tada, Kenshi Hayashi, Masayuki Takamura, Masa-aki Kawashiri, Philip Greenland
Journal: Circulation (2020)

Introduction: First-degree atrioventricular block (fAVB) is a common cardiac conduction disorder diagnosed by prolongation of the PR interval ≥220 msec. Although it is generally considered benign, some previous studies demonstrated that fAVB was associated with incident atrial fibrillation (AF). However, evidence is scarce regarding the association between fAVB and incident AF in older populations. Hypothesis: We hypothesized that fAVB was significantly associated with incident AF in older populations. Methods: Eligible participants were residents in Kanazawa City who aged ≥ 40 years and underwent 12-lead ECG at the national Japanese health checkups in 2013. Participants with AF detected at the baseline exam and with no follow-up examinations between 2014 and 2018. fAVB was defined as PR interval ≥ 220 msec based on the Minnesota code (6-3). Incident AF was defined as the first episode of AF detected by 12-lead ECG at the annual health checkups. The cumulative incidence of AF was estimated by the Kaplan Meier curve analysis, and statistical significance was evaluated by the log-rank test. Unadjusted and adjusted hazard ratios (HRs) were computed by the Cox proportional hazard model. HRs were adjusted using three models in which conventional risk factors for AF were included (Table). Results: 37,730 participants (mean age, 72.3 ± 9.6 years; Male, 37%) were included. Baseline fAVB was observed in 667 (1.8%) participants. During the median follow-up period of 5 years (interquartile range, 4.0 - 5.0 years), 691 cases of incident AF were observed. Kaplan Meier curve showed that a 5-year cumulative incidence of AF was significantly higher in fAVB (+) group compared with fAVB (-) group (6.8% vs 2.1%, p &lt; 0.01). In the fully adjusted model, fAVB was significantly associated with incident AF (HR, 1.75; 95% confidence interval, 1.25 - 2.45; p-value &lt; 0.01) (Table). Conclusion: fAVB was independently associated with incident AF in this predominantly elderly Japanese population.
Abstract 15455: Prevalence of Subclinical Myocardial Dysfunction in Hospitalized Patients With Covid-19 and Association With In-hospital Mortality
Authors: Anum Minhas, Nisha A Gilotra, Erin Goerlich, Brian T Garibaldi, Thomas S Metkus, Garima Sharma, Nicole Bavaro, Susan Phillip, Erin D Michos, Allison G Hays
Journal: Circulation (2020)

Introduction: Acute cardiac injury has been reported in COVID-19. However, the extent of subclinical myocardial dysfunction on imaging has not been characterized. We determined the prevalence of myocardial dysfunction using speckle tracking echocardiography (STE) in hospitalized COVID-19 patients and its association with cardiovascular risk factors and mortality. Methods: We retrospectively studied hospitalized COVID-19 patients undergoing echocardiography with STE (n=83). We investigated the association of global longitudinal strain (GLS) and myocardial work efficiency (MWE), a load independent measure of myocardial function, with clinical parameters. Logistic regression was used to examine associations of GLS and MWE with in-hospital mortality. Abnormal left ventricular ejection fraction (LVEF) was defined as &lt;50%. Abnormal GLS and MWE were defined as &gt;-18% and &lt;95%, respectively. Results: Mean age was 66±14 years and 59% were men. There were 16/83 (19%) with reduced LVEF (&lt;50%), while 64% (53/83) had abnormal GLS (&gt;-18%) and 79% (59/75) had abnormal MWE (&lt;95%) ( Figure ). Patients with abnormal GLS had higher body mass index (BMI) (32±8 vs 28±5 kg/m 2 , p=0.016) and more frequent diabetes (47 vs 23%, p=0.03) and patients with abnormal MWE had more frequent diabetes (49 vs 6%, p=0.002), compared to normal. Higher MWE was associated with lower mortality unadjusted (OR 0.92 [95% CI 0.85-0.99]; p=0.048) and after adjusting for age, sex, diabetes, hypertension, and coronary artery disease (OR 0.87 [95% CI 0.78-0.97]; p=0.014). This remained true on sensitivity analysis of only those with normal LVEF, adjusting for age and sex (n=61). GLS and LVEF were not associated with mortality. Conclusions: Abnormal myocardial function is prevalent in hospitalized COVID-19 patients undergoing STE. Higher MWE was associated with lower in-hospital mortality. Larger studies are warranted to determine the prognostic role of sensitive markers of LV function in COVID-19.
Abstract 14307: Reduction in the Risk of Major Adverse Cardiovascular Events With Apabetalone, a Bet Protein Inhibitor, in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes According to Insulin Treatment: Analysis of the Betonmace Trial
Authors: Gregory G Schwartz, Stephen J Nicholls, Henry Ginsberg, Jan JOHANSSON, Kamyar Kalantar-Zadeh, Ewelina Kulikowski, Peter P Toth, Norman Wong, Michael Sweeney, Kausik K Ray
Journal: Circulation (2020)

Introduction: Use of insulin has been associated with worse CV outcomes in patients (pts) with type 2 diabetes T2D. Apabetalone (APB) is a novel selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. In the Phase 3 BETonMACE trial treatment with APB, compared with placebo, resulted in non-significantly fewer major adverse CV events (MACE: CV death, non-fatal MI or stroke) in 2425 pts with T2D and recent acute coronary syndrome (ACS). Objective: In this analysis of BETonMACE we examined the relationship of insulin use to MACE risk and its modification by APB. Methods: Baseline characteristics were compared in insulin-treated (INS) or not insulin-treated (no-INS) pts. The incidence of MACE and treatment hazard ratio (HR) were compared between these two subgroups. Results: 829 (34.2%) pts received insulin at baseline, with or without other diabetes drugs. INS vs no-INS pts were more likely to be female (29 vs 24%), had longer duration of T2D (12.6 vs 6.4 yrs), higher HbA1c (8.4 vs 6.9%) and baseline glucose (156 vs 126 mg/dL), lower use of metformin (73 vs 87%) and sulfonylureas (21 vs 33 %), and higher use of SGLT2 inhibitors (16 vs 6%) and GLP1 receptor agonists (10 vs 2%). MACE in the placebo group was higher in INS than no-INS (17.4% vs 9.7%; HR 1.94; 95% CI 1.39-2.73; p=0.0001). Overall, APB was associated with fewer MACE (HR 0.82, 95% CI 0.65-1.04, p=0.11). The relative reduction in MACE with ABP was similar in INS (HR 0.78, 95% CI. 0.55-1.10, p=0.16) and no-INS (HR 0.87, 95% CI 0.63-1.21, p = 0.42, p interaction =0.64). The absolute reduction in MACE with APB was numerically greater among INS than non-INS (3.69 vs 1.30%). Conclusions: Pts with T2D and recent ACS treated with insulin are at high risk for MACE. High risk of MACE with insulin use is likely through association with other clinical characteristics prognostic for MACE. Insulin treatment may be a marker to identify pts with potential for large absolute reduction in MACE with APB.
Abstract 16347: Simplified Workflow to Improve the Precision of Non-invasive Radio-ablation of Ventricular Tachycardia Storm
Authors: Gordon Ho, Todd Atwood, Andrew Bruggeman, Kevin Moore, Elliot R McVeigh, Christopher Villongco, Frederick Han, Jonathan C Hsu, Kurt S Hoffmayer, Farshad Raissi, Gregory K Feld, Arno J Mundt, David E Krummen
Journal: Circulation (2020)

Background: Stereotactic ablative radiotherapy (SAbR) is an emerging therapy for ventricular tachycardia (VT) storm, but the feasibility and outcomes guided by computational 12-lead ECG mapping and respiratory-gated radiation delivery have not been reported. Hypothesis: We hypothesized that a novel 12-lead ECG-based mapping system and respiratory-gated radiotherapy delivery may simplify the workflow and improve precision of SAbR in critically ill patients with VT storm. Methods: We enrolled patients with VT storm who were not candidates for catheter ablation. VT was induced using non-invasive stimulation and recorded on 12-lead ECGs. Computational ECG mapping was performed to localize VT exit sites. Target volumes were contoured onto an averaged free-breathing CT. Ionizing radiation (25 Gy) was delivered using a linear accelerator (Varian, Palo Alto). In patients with significant respiratory motion, radiotherapy was delivered at end-expiration, guided by ICD lead fiducials. Results: In 5 patients (age 74±6.1 years, EF 29±14%) refractory to 2±1 ablation procedures, 1.5±0.6 VT morphologies were localized on 3D models (Fig 1A) using ECG-based mapping (mapping time 1.2±0.3 min). In patients whom respiratory gating (Fig 1B) was used prospectively due to respiratory variation, the planned target volume (PTV) was smaller compared to patients who were not gated (71 ± 7 vs 153 ± 35 cc, p&lt;0.01). These patients also had VT targets (crux or inferior LV) close to the stomach, and did not experience adverse events. ICD shocks were decreased after SAbR compared to before (0.25±0.5 vs 26±19 shocks, p&lt;0.001) at 4.4±3.4 months follow-up. Conclusion: Non-invasive computational mapping based upon the 12-lead ECG alone simplifies radioablation workflow in critically ill VT storm patients and reduces the burden of ICD shocks. Respiratory gated radiotherapy ablation appears feasible and may help reduce target volume of therapy. Studies with longer follow-up are ongoing.
Abstract 13165: Self-Reported Social Functioning is Responsive to Change in Functional Class in Patients With a Left Ventricular Assist Device: Findings From the Mechanical Circulatory Support Measures of Adjustment and Quality of Life Study
Authors: Elizabeth A Hahn, Peter D Cummings, Katy Wortman, Joann Lindenfeld, Jeffrey Teuteberg, Michael S Kiernan, Larry A Allen, Colleen K McIlvennan, Christopher S Lee, Quin E Denfeld, Liviu Klein, David Beiser, Catherine M Murks, Jonathan D Rich, Duc T Pham, Clyde W Yancy, David Cella, Mary N Walsh, Bernice Ruo, Sarah K Buono, Kathleen L Grady
Journal: Circulation (2020)

Introduction: Improvement in social functioning is an important goal for advanced heart failure (HF) patients (pts) who receive left ventricular assist devices (LVADs). Self-reported social functioning and its association with clinical change is understudied. Methods: Adult HF pts who received LVADs at nine U.S. sites completed two measures of social functioning prior to, and 3-6 months after, surgery. Patient-Reported Outcomes Measurement Information System (PROMIS) measures were: Ability to Participate in Social Roles and Activities (Ability) and Satisfaction with Social Roles and Activities (Satisfaction). PROMIS uses T-scores standardized to a U.S. general population (mean=50; standard deviation, SD=10); higher scores represent better outcomes. New York Heart Association (NYHA) Functional Classification was assigned at both times by treating clinicians; change was subsequently categorized as Better, Same or Worse NYHA. Linear mixed effects models and least-squares means were estimated for Ability and Satisfaction. Results: Pts ( n =107) were primarily male (78%) and non-Hispanic White (68%); mean age (SD)=54 (12.5) years; 74% were NYHA Class IV prior to surgery and only 18% were NYHA IV at follow-up. NYHA was better for the majority ( n =75, 70%); 24% ( n =26) were the same, and 6% ( n =6) were worse. Mean Ability and Satisfaction were lower than the general population mean of 50 at both time points (Figure). Ability improved for the NYHA Better ( p &lt;0.001) and Same ( p =0.030) groups, and nominally decreased for the Worse group ( p =0.800). Satisfaction improved for the Better ( p &lt;0.001) group, and nominally improved for the Same and Worse groups ( p &gt;0.300). Conclusions: Self-reported social functioning measures were responsive to clinician-rated clinical change. Understanding these relationships may guide clinicians in providing targeted health-related quality of life therapies to improve social functioning.
Association Between Wearable Device–Based Measures of Physical Frailty and Major Adverse Events Following Lower Extremity Revascularization
Authors: Bijan Najafi, Narek Veranyan, Alejandro Zulbaran-Rojas, Catherine Park, Hung Nguyen, Quinn Kaleikaumaka Nakahara, Hector Elizondo-Adamchik, Jayer Chung, Joseph L. Mills, Miguel Montero-Baker, David G. Armstrong, Vincent Rowe
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Physical frailty is a key risk factor associated with higher rates of major adverse events (MAEs) after surgery. Assessing physical frailty is often challenging among patients with chronic limb-threatening ischemia (CLTI) who are often unable to perform gait-based assessments because of the presence of plantar wounds. <h3>Objective</h3> To test a frailty meter (FM) that does not rely on gait to determine the risk of occurrence of MAEs after revascularization for patients with CLTI. <h3>Design, Setting, and Participants</h3> This cohort study included 184 consecutively recruited patients with CLTI at 2 tertiary care centers. After 32 individuals were excluded, 152 participants were included in the study. Data collection was conducted between May 2018 and June 2019. <h3>Exposures</h3> Physical frailty measurement within 1 week before limb revascularization and incidence of MAEs for as long as 1 month after surgery. <h3>Main Outcomes and Measures</h3> The FM works by quantifying weakness, slowness, rigidity, and exhaustion during a 20-second repetitive elbow flexion-extension exercise using a wrist-worn sensor. The FM generates a frailty index (FI) ranging from 0 to 1; higher values indicate progressively greater severity of physical frailty. <h3>Results</h3> Of 152 eligible participants (mean [SD] age, 67.0 [11.8] years; 59 [38.8%] women), 119 (78.2%) were unable to perform the gait test, while all could perform the FM test. Overall, 53 (34.9%), 58 (38.1%), and 41 (27.0%) were classified as robust (FI &lt;0.20), prefrail (FI ≥0.20 to &lt;0.35), or frail (FI ≥0.35), respectively. Within 30 days after surgery, 24 (15.7%) developed MAEs, either major adverse cardiovascular events (MACE; 8 [5.2%]) or major adverse limb events (MALE; 16 [10.5%]). Baseline demographic characteristics were not significantly different between frailty groups. In contrast, the FI was approximately 30% higher in the group that developed MAEs (mean [SD] score, 0.36 [0.14]) than those who were MAE free (mean [SD] score, 0.26 [0.13];<i>P</i> = .001), with observed MAE rates of 4 patients (7.5%), 7 patients (12.1%), and 13 patients (31.7%) in the robust, prefrail and frail groups, respectively (<i>P</i> = .004). The FI distinguished individuals who developed MACE and MALE from those who were MAE free (MACE: mean [SD] FI score, 0.38 [0.16];<i>P</i> = .03; MALE: mean [SD] FI score, 0.35 [0.13];<i>P</i> = .004) after adjusting by body mass index. <h3>Conclusions and Relevance</h3> In this cohort study, measuring physical frailty using a wrist-worn sensor during a short upper extremity test was a practical method for stratifying the risk of MAEs following revascularization for CLTI when the administration of gait-based tests is often challenging.
Diabetes Management in Chronic Kidney Disease: Synopsis of the 2020 KDIGO Clinical Practice Guideline
Authors: Sankar D. Navaneethan, Sophia Zoungas, M. Luiza Caramori, Juliana C.N. Chan, Hiddo J.L. Heerspink, Clint Hurst, Adrian Liew, Erin D. Michos, Wasiu A. Olowu, Tami Sadusky, Nikhil Tandon, Katherine R. Tuttle, Christoph Wanner, Katy G. Wilkens, Lyubov Lytvyn, Jonathan C. Craig, David J. Tunnicliffe, Martin Howell, Marcello Tonelli, Michael Cheung, Amy Earley, Peter Rossing, Ian H. de Boer, Kamlesh Khunti
Journal: Annals of Internal Medicine (2020)

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD). Methods: The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized. Recommendations: The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.
Mediastinal germ cell tumors: many questions and perhaps an answer
Authors: J. Wolter Oosterhuis, Leendert H.J. Looijenga
Journal: Journal of Clinical Investigation (2020)

Some germ cell tumors (GCTs) in men develop into hematologic malignancies; however, the clonal origins of such malignancies remain unknown. In this issue of the JCI, Taylor, Donoghue, et al. unravel the clonal relationship between primary mediastinal nonseminomas (PMNs) and hematologic somatic-type malignancies (HSTMs). Whole-exome sequencing was used to construct phylogenetic trees of the PMNs and the ensuing HSTM clones. HSTMs were derived from multiple distinct clones not detected within the PMNs. Clones from PMNs and HSTMs shared a common precursor, arguably an embryonal carcinoma cell resulting from a reprogrammed primordial germ cell from the thymus. Mutational and copy number variation analysis of a large cohort of patients with PMNs also demonstrated a high prevalence of TP53 mutations not found in testicular nonseminomas. These data likely explain why patients with PMNs are frequently resistant to platinum-based chemotherapy and provide TP53 mutations as potential targets.
Angiotensin converting enzyme genotypes and mortality from COVID-19: An ecological study
Authors: Ar K Aung, Tess Aitken, Bing M Teh, Christiaan Yu, Richard Ofori-Asenso, Ken L Chin, Danny Liew
Journal: Journal of Infection (2020)

Angiotensin converting enzyme (ACE) genotypes are known to be associated with development of acute respiratory distress syndrome (ARDS) and resultant mortality. In the present study, we examined the association between distribution frequency of ACE genotypes and COVID-19 mortality.We undertook an ecological study to examine the association between ACE genotypes and COVID-19 mortality across 25 countries to represent different geographical regions of the world. The population frequencies of ACE genotypes were drawn from previously published reports and data on COVID-19-related mortality were extracted from 'Worldometer'. Multivariable analyses were also undertaken adjusting for age (median age), sex (percentage of females) and the number of COVID-19 tests undertaken. Associations between genotypes deletion/deletion (DD) and insertion/insertion (II) prevalence and COVID-19-related mortality (per million people per day since the first diagnosed case) were evaluated.The frequency of II genotype is highest in east Asian countries and lower among the European and African countries. An inverse geographical distribution frequency was noted for DD genotype. Increasing II genotype frequency was significantly associated with decreased COVID-19 mortality rates (adjusted incident rate ratio [IRR] 0.3, 95% confidence interval [CI]: 0.002-0.7, p = 0.03). However, no association was found between DD genotype frequency and COVID-19 mortality rates (adjusted IRR 4.3, 95% CI: 0.5-41.2, p = 0.2).Distribution frequency of ACE insertion/insertion (II) genotype may have a significant influence on COVID-19 mortality. This information has potential utility for resource planning at a systemic level, as well as for clinical management.
SARS-CoV-2 has displaced other seasonal respiratory viruses: Results from a prospective cohort study
Authors: Stephen Poole, Nathan J. Brendish, Tristan W. Clark
Journal: Journal of Infection (2020)

ObjectivesThe effect of SARS-CoV-2 on existing respiratory viruses in circulation and the overall burden of viral respiratory disease remains uncertain. Traditionally, severe viral respiratory disease disproportionally affects those with underlying chronic lung diseases. This study aimed to assess the impact of SARS-CoV-2 on the prevalence and clinical characteristics of respiratory virus disease in hospitalised adults.MethodsData for this cohort study were from hospitalised adults who had multiplex PCR testing for respiratory viruses over several seasons in Hampshire, UK. Respiratory virus detection during the first epidemic peak of SARS-CoV-2 was compared to detection during the same time period across previous years.Results856 patients had multiplex PCR for respiratory viruses between March and May over 5 years. Before 2020, a non-SARS-CoV-2 virus was detected in 54% patients (202/371) compared to 4.1% (20/485) in 2020 (p < 0.0001). SARS-CoV-2 was associated with asthma or COPD exacerbations in a smaller proportion of infected patients compared to other viruses (1.0% vs 37%, p < 0.0001).ConclusionsThe emergence of SARS-CoV-2 was associated with substantial reductions in the circulation of seasonal respiratory viruses and large differences in the characteristics of viral-associated disease, including illness in a greater proportion of patients without underlying lung disease.
Abstract 13107: Nitroglycerin Pretreatment Induces Metabolic Tolerance to Spinal Cord Ischemia-reperfusion Injury Through Nitric Oxide-mediated Mitochondrial Katp Channel Activation
Authors: Yuki Ikeno, Christian V Ghincea, Gavriel Roda, Linling Cheng, Muhammad Aftab, Xianzhong Meng, Michael Weyant, Joseph Cleveland, David A Fullerton, Thomas B Reece
Journal: Circulation (2020)

Introduction: Pharmacologic induction of metabolic tolerance to spinal cord ischemia-reperfusion injury (SCI) after thoracoabdominal aortic intervention is not well established. We previously demonstrated that nicorandil pretreatment preserved motor function in a murine SCI model via direct mitochondrial ATP-sensitive potassium (KATP) channel activation and nitric oxide (NO) donation. However, the independent role of NO-mediated neuroprotection has not been elucidated. Hypothesis: Nitroglycerin pretreatment will induce neuroprotection through NO-mediated KATP channel activation. Methods: SCI was induced by 7 minutes of thoracic aortic cross-clamping in adult male C57BL/6 mice. Pretreatment constituted intraperitoneal injection 3 consecutive days before injury. Experimental groups: sham (no pretreatment or ischemia, n=10), SCI control (normal saline, n=20), nitroglycerin 1 mg/kg (n=18), nitroglycerin 1 mg/kg + 5-hydroxydecanonate 5 mg/kg (5HD, mitochondrial KATP channel blocker, n=13), 5HD 5 mg/kg (n=10), nitroglycerin 1 mg/kg + carboxy-PTIO (cPTIO) 1 mg/kg (NO scavenger, n=16), and cPTIO 1 mg/kg (n=10). Limb motor function and the number of viable neurons within the anterior horn of the spinal cord were evaluated. Results: Compared to SCI control, motor function was significantly preserved in the nitroglycerin pretreatment group at every time point after ischemia. In the nitroglycerin+5HD and nitroglycerin+cPTIO groups, motor preservation was significantly attenuated compared to nitroglycerin pretreatment (p&lt;0.001). Histological analysis showed significant neuron preservation in the nitroglycerin pretreatment group compared with SCI control (p=0.011). This preservation was completely attenuated with 5HD or cPTIO co-administration (p=0.001). Conclusions: Nitroglycerin pretreatment significantly preserved motor function in a murine SCI model through NO-mediated KATP channel activation.