tbuckley/cabot-search huggingface dataset:
Abstract 12596: Manipulation of Gut Microbiota Influences Myocardial Mass in Mice
Authors: Takehiro Kamo
Journal: Circulation (2020)

Introduction: Gut microbiota have developed a close relationship with human host during the co-evolutionary process for millions of years, and they play an essential role in the maintenance of host homeostasis. There is accumulating evidence that an imbalance in the gut microbial communities, referred to as dysbiosis, is associated with human pathologies including cardiovascular diseases. We and others have recently demonstrated that heart failure is associated with gut microbiota dysbiosis using 16S ribosomal RNA gene sequencing of fecal samples from patients with heart failure. This finding suggests a potential significance of gut microbiota in the pathophysiology of heart failure. However, the link between the gut microbiota and the heart remains largely unclear. Hypothesis: We hypothesized that manipulation of gut microbiota influences the structure of the heart. Methods: To determine the effects of gut microbiota depletion, cardiac structure and gene expression were evaluated in mice following treatment with orally administered broad-spectrum antibiotic cocktail. We subsequently explored the effects of administration of a single antibiotic agent on myocardial structure. Results: Antibiotic cocktail-treated mice showed a remarkable decrease in myocardial mass and cardiomyocyte size as compared with untreated mice (mean [±SD] ratio of heart weight to body weight, 3.87±0.25 mg/g in 44 antibiotic-treated mice vs. 4.38±0.21 mg/g in 45 untreated mice). The decrease in myocardial mass was associated with substantial changes in gene expression profiles in the heart, including the expression of genes encoding sarcomere proteins and extracellular matrix proteins. In addition, oral treatment with ampicillin alone led to a significant decrease in myocardial mass (mean [±SD] ratio of heart weight to body weight, 3.52±0.24 mg/g in 11 ampicillin-treated mice vs. 4.10±0.24 mg/g in 12 untreated mice). Conclusions: These results suggest that gut microbiota may modulate myocardial mass through the remote regulation of gene expression in the heart. Our study indicates an intimate relationship between the gut microbiota and the heart, and suggests the potential efficacy of manipulating gut microbiota in the prevention and treatment of heart failure.
Abstract 121: A Pre-Clinical Randomized Blinded Trial of Inhaled Nitric Oxide During Pediatric Cardiopulmonary Resuscitation
Authors: Ryan W Morgan, Robert M Sutton, Adam S Himebauch, Anna L Roberts, William P Landis, Marco Hefti, Vinay M Nadkarni, Robert A Berg, Todd J Kilbaugh
Journal: Circulation (2020)

Introduction: Inhaled nitric oxide (iNO) may result in higher systemic BP during CPR and may have a neuroprotective role post-arrest, but its effects on cerebral perfusion pressure (CePP), cerebral blood flow (CBF), and mitochondrial function when administered during CPR are unknown. Hypotheses: We hypothesized that administration of iNO during CPR would lead to higher CePP, higher CBF, and less brain injury as measured by cerebral mitochondrial function, neuronal apoptosis, and microglial activation. Methods: In 1-month-old swine (n=20), lipopolysaccharide was intravenously infused to induce a shock state, followed by induction of VF and treatment with hemodynamic-directed CPR (HD-CPR). Animals were randomized to blinded treatment with either: 1) HD-CPR with iNO (beginning 1 minute into CPR), or 2) HD-CPR without iNO. Defibrillation attempts began at 10 minutes with a maximum CPR duration of 20 minutes. Among animals surviving 1-hour post-arrest, cerebral tissue underwent high-resolution respirometry to evaluate the mitochondrial electron transport system and quantification of neuronal apoptosis and microglial activation. Chi-square test, Fisher’s exact test, Student’s t-test, Wilcoxon rank-sum test, and a generalized estimating equation regression model compared the two groups. Results: During CPR, the iNO group had higher mean aortic pressure (41.6±2.0 vs. 36.0±1.4 mmHg; p=0.005); diastolic BP (32.4±2.4 vs. 27.1±1.7 mmHg; p=0.03); CePP (25.0±2.6 vs. 19.1±1.8 mmHg; p=0.02); and CBF relative to pre-CPR baseline (243.2±54.1 vs. 115.5±37.2%; p=0.02). Among the 8/10 survivors in each group, the iNO group had higher mitochondrial Complex I oxidative phosphorylation in the cerebral cortex (3.60 [3.56, 3.99] vs. 3.23 [2.44, 3.46] pmol O 2 /s*mg; p=0.01) and hippocampus (4.79 [4.35, 5.18] vs. 3.17 [2.75, 4.58] pmol O 2 /s*mg; p=0.02). There were no other differences in mitochondrial respiration or brain injury between groups. Conclusions: Blinded treatment with iNO during CPR in a model of pediatric shock-associated cardiac arrest resulted in superior CePP, CBF, and cerebral mitochondrial Complex I respiration. These data suggest that iNO treatment during CPR may lead to improved neurologic outcomes from pediatric cardiac arrest.
Abstract 16289: Deformation of Tricuspid Annulus After Tricuspid Ring Annuloplasty: A Three-dimensional Transesophageal Echocardiography Study
Authors: Atsushi Hayashi, Jun Akashi, Yosuke Nabeshima, Mai Iwataki, Yutaka Otsuji
Journal: Circulation (2020)

Background: Tricuspid ring annuloplasty (TAP) is usually performed for patients with mild or greater functional tricuspid regurgitation (TR) at the time of left-sided valve surgery. However, there were limited data regarding the shape of tricuspid annulus after TAP. The aim of this study was using three-dimensional (3D) transesophageal echocardiography to investigate the impact of the ring annuloplasty on the tricuspid annulus after TAP. Methods: 3D tricuspid valve was retrospectively analyzed in 20 patients who underwent concomitant left-sided heart surgery and TAP for functional TR. 3D data of tricuspid valve were acquired before TAP, immediate after surgery (intraoperative), and before discharge (15±5 days after TAP). TAP was performed by one surgeon using a Carpentier-Edwards Physio Tricuspid annuloplasty ring. The ring size was determined by measuring the distance from anteroseptal to posteroseptal commissures. 3D tricuspid annular area was measured. The area protruded outside the annuloplasty ring was obtained by subtracting the ring area from the annular area (Figure). Results: All 20 patients underwent successfully TAP with less than mild residual TR. Annuloplasty rings size 28mm, 30mm, 32mm, and 34mm were used in 6 (30%), 4 (20%), 5 (25%), and 5 (25%) patients, respectively. Median annular area decreased from 1074 (interquartile rage 893-1276) mm 2 before TAP to 591 (519-706) mm 2 immediate after TAP, but showed significant increase to 645 (501-766) mm 2 at the time of discharge (P&lt;0.001). Percent area protruded outside the annuloplasty ring was 14% immediate after TAP and increased to 24% before discharge (P&lt;0.001). Before discharge, there were 9 patients with more than mild residual TR (2 had moderate TR). Percent area protruded outside the annuloplasty ring was associated with mild or more residual TR at the discharge. Conclusion: Tricuspid annular shape after TAP was not always round. Deformation of tricuspid annulus may be associated with residual TR.
Abstract 13885: Phenotyping Risk Profiles for Heart Failure With Preserved and Reduced Ejection Fraction Among Breast Cancer Survivors
Authors: Alexi Vasbinder, Richard Cheng, Roberta Ray, Dale Langford, Ana Barac, Garnet Anderson, Michael Simon, Bette Caan, Mary Branch, Aladdin Shadyab, Abu Taiyab Nazmus Saquib, Kerryn Reding
Journal: Circulation (2020)

Introduction: Breast cancer (BC) survivors (BCS) are at increased risk for incident heart failure (HF). In this population, the risk for HF with preserved ejection fraction (HFpEF) has been understudied compared to HF with reduced EF (HFrEF). The purpose of this study was to estimate 1) the incidence of HFpEF and HFrEF, and 2) the phenotypic profiles conferring risk for incident HFpEF and HFrEF in BCS. Methods: This Women’s Health Initiative analysis was conducted in women with invasive BC stages I-IV in the Medical Records Cohort (MRC). Those with pre-existing HF were excluded. Exposures of interest were lifestyle factors [e.g. body mass index (BMI)], comorbidities [e.g. hypertension, diabetes, and myocardial infarction (MI)], and BC treatment. Lifestyle factors and comorbidities most proximal and prior to BC diagnosis were assessed. In the MRC, BC and HF as well as left ventricular EF (LVEF) were ascertained through chart review and physician-adjudication. LVEF ≥50% was classified as HFpEF; and &lt;50% for HFrEF per AHA/ACC guidelines. Cox proportional hazards models estimated risks of HFpEF and HFrEF. Follow up time began at BC diagnosis and HF events were recorded through March 1, 2019. All models adjusted for age at BC diagnosis. Results: In 2,250 BCS, 153 developed HF after BC during a median follow-up of 7.3 years. Of those, 49 had HFrEF and 75 had HFpEF. The cumulative incidences of HFrEF and HFpEF over follow-up were 7.3% and 4.6%, respectively. Diabetes and MI were associated with both HFpEF and HFrEF (Table). Smoking, BMI ≥30, and hypertension were associated with HFpEF. Anthracycline use was associated with HFrEF but not HFpEF (p=0.03). Conclusions: In BCS, lifestyle factors were associated with incident HFpEF, whereas anthracycline use was associated with a higher risk for HFrEF. Understanding risk factors associated with incident HFpEF and HFrEF in BCS is important to guide the implementation of risk profile-specific preventative measures and interventions.
“Hot Cord” Sign on 18F-FDG PET/CT in a Patient With Acute Myelitis Due to Neuromyelitis Optica Spectrum Disorder
Authors: Maryam Ahmed Alkhaja, Lenith Tai Jit Cheng, Hoi Yin Loi, Arvind Kumar Sinha
Journal: Clinical Nuclear Medicine (2020)

A 44-year-old woman presented with prolonged low-grade fever, bilateral upper limb weakness, and hyperesthesia. MRI showed hyperintense T2 signal and enhancement of the cervicothoracic spinal cord. F-FDG PET/CT was requested to investigate pyrexia of unknown origin. It demonstrated diffusely increased FDG uptake along the entire spinal cord, suggestive of extensive acute myelitis. Initial blood work was positive for antinuclear antibodies and anti-Ro/SSA antibodies. Cerebrospinal fluid analysis revealed lymphocytosis and detected the presence of neuromyelitis optica aquaporin-4-immunoglobulin G antibodies, fulfilling the criteria for diagnosis of neuromyelitis optica spectrum disorder.
Abstract 16420: Double Internal Thoracic Artery Grafts are Associated to Better 10-year Outcomes After Coronary Artery Bypass Grafting
Authors: Fabio Barili, Paola DErrigo, Stefano Rosato, Mariangela D'Ovidio, Fausto Biancari, Eva Pagano, Alessandro Parolari, Fulvia Seccareccia
Journal: Circulation (2020)

Introduction: Few data on long-term follow-up of effectiveness and advantages related to the employ of double internal thoracic artery grafts (BITA) for coronary artery bypass grafting are available and the advantage of the employ of BITA have been recently questioned. Hypothesis: This observational cohort study was designed by the PRIORITY planning committee to evaluate 10-year follow-up of isolated CABG performed with and without BITA in order to evaluate the impact of BITA on long-term outcomes. Methods: The PRIORITY project was designed to evaluate the long-term outcomes of 2 large prospective multicenter cohort studies on CABG conducted between 2002-2004 and 2007-2008. Data on isolated CABG were linked to 2 administrative datasets. The primary endpoints were death and major adverse cardiac events (MACEs) at follow-up. Time-to-event data were analyzed using Kaplan-Meier estimates and Cox regression. Models generation was performed on the full dataset and the validation was performed with Montecarlo simulations. Results: The population consisted of 11021 patients who underwent isolated CABG; double thoracic internal artery grafts was employed in 23.5%. The median follow-up time was 7.9 years (interquartile range 7.4 - 10 years). After adjustment for potential confounding factors, BITA was significantly associated with better survival (HR 0.81, 95%CI 0.73-0.89, p &lt; 0.001). Moreover, the employment of BITA reduced the incidence of MACEs at follow-up (adjusted HR 0.83, 95%CI 0.77-0.89, p &lt; 0.001). In details, BITA was demonstrated to be a protective factor for acute myocardial infarction (adjusted HR 0.83, 95%CI 0.72-0.96, p = 0.001) and for rehospitalization for percutaneous cardiac intervention (PCI; adjusted HR 0.72, 95%CI 0.63-0.84, p &lt; 0.001). Conclusions: The employment of double internal thoracic artery grafts for coronary artery bypass grafting has been associated to significant survival advantage at long-term. Moreover, it is a protective factor for acute myocardial infarction and rehospitalization for percutaneous cardiac intervention, reducing the hazard by 28%.
Abstract 13723: Racial/ethnicity and Education Disparities in Hypertension Among U.s. Adults and the Role of Nutrient Quality -- The International Study on Macro/micronutrients (intermap)
Authors: Thanhhuyen T Vu, Linda VAN HORN, Queenie M Chan, Rachel Gibson, Martha L DAVIGLUS, Jeremiah Stamler
Journal: Circulation (2020)

Background: Limited education and/or being Black are inversely associated with hypertension in the US. Whether nutrient quality influences these associations remains unclear. Methods: Diet and blood pressure (BP) were measured in 2,195 US adults ages 40-59 years between 1996-99 in the INTERMAP study. Hypertension was defined by 2017 standards—SBP/DBP ≥130/80 mmHg or on BP medication. OMNIHEART-like nutrient score defined nutrient quality (see Table footnote). Higher-education was defined as 17+years of school. Results: Participants were 50% female, 56.2% non-Hispanic (NH) White, 17.4% NH-Black, 12.7% Japanese, 13.6% Hispanic, 24% higher-education, and 42% hypertensive. With multiple adjustments without nutrient score, we observed racial disparity on hypertension in NH-Black vs. NH-White across education levels, and it was more pronounced in the higher-education group; i.e., in the lower-education group, compared to NH-White, relative risk—RR (95% CI) of hypertension in NH-Black was 1.4(1.2-1.6); but it was 2.0 (1.5-2.6) in the higher-education group. Education disparity was seen in NH-White—(RR was 42% lower in those with higher vs. lower-education. Added nutrient score slightly attenuated observed associations (see Table). Nutrient score was also independently associated with hypertension; i.e., compared to the 5 th quintile, RR (95%CI) of hypertension in the 1 st quintile was 1.3(1.1-1.5). There were no interactions of nutrient score with race/ethnicity/education. BMI levels attenuated race/ethnicity/education-hypertension relations and diminished the nutrient profile-hypertension relation. Conclusion: Education levels modified racial disparity between NH-Black and White but maintained independent effects on hypertension, especially in NH-White. Differences in nutrient quality did not account for race/ethnicity/education disparities on hypertension, rather independent effects were largely explained by BMI levels.
Abstract 13892: Self-care is Poor in Lay Caregivers of Patients With Heart Failure, Especially If Caring More Than Eight Hours Daily
Authors: Austin Matus, Gladys Thomas, Jenna Garo, Michela Luciani, Davide Ausili, Barbara Riegel
Journal: Circulation (2020)

Introduction: Most patients with HF are living at home with care provided to them by loved ones. Informal caregiving is demanding and stressful, may exceed the caregiver’s ability to adapt, and many eventually become care recipients themselves. Engaging in self-care may improve caregivers’ health. Purpose: To describe the self-care behaviors of HF caregivers and compare self-care behaviors based on hours of daily caregiving. Methods: Using a cross-sectional design, we analyzed enrollment data from lay caregivers in the iCare4Me clinical trial testing the efficacy of a virtual support intervention promoting caregiver self-care. All caregivers were providing informal care to someone with HF for ≥ 8 hours/week. Self-care behaviors were measured with two instruments: Health Self-Care Neglect scale (9 dichotomous items summed for a final score) and the Self-Care Inventory (3 scales: Self-Care Maintenance, Monitoring, and Management with standardized scores 0-100; higher scores, better self-care). A Health Self-Care Neglect score ≥ 2 is considered poor self-care. A Self-Care inventory score &lt; 70 is considered inadequate. Hours of caregiving were self-reported. Results: The sample (n=40) was mostly older adults (56 ± 13.2 years, female 97.5%) and many were Black (37.5%). Caregivers reported caregiving (10.8± 8.4 hours/day, range 1-24 hours/day). Differences in self-care were observed between those caregiving &gt; 8 hours (n=18, 18.4 ± 6.6) vs. ≤ 8 hours/day (n=22, 4.6± 2.6). Mean Health Self-Care Neglect was higher in caregivers reporting ≥ 8 hours/day compared to &lt; 8 hours (6.7 ± 2.0 vs. 4.9 ± 2.1, p=0.004). The most commonly neglected areas of self-care were “Put off recreational activities you enjoy” and “Taken medications improperly”. All Self-Care Inventory scale scores were inadequate (Maintenance 69.1 ± 17.1, Monitoring 63.7 ± 21.8, Management 58.2 ± 18.9). Those providing care for ≥ 8 hours/day reported significantly poorer Self-Care Maintenance (64.1 ± 11.7 vs. 73.9 ± 19.4, p=0.03). Conclusion: Self-care is poor in all the caregivers, but especially among those responsible for caregiving relatively more hours/day. Interventions to improve caregivers’ self-care are needed.
Abstract 14523: N-acetylcysteine for the Prevention of Atrial Fibrillation After Noncardiac Thoracic Surgery: A Double-blind, Randomized, Placebo-controlled Trial
Authors: David AMAR, Hao Zhang, Mina K Chung, Kay See Tan, Dawn P Desiderio, Bernard Park, Alessia Pedoto, Nancy Roistacher, James Isbell, Daniela Molena, Ginger Milne, Bryan F Meyers, Valerie W Rusch, David R Jones
Journal: Circulation (2020)

Introduction: Adding N-acetylcysteine (NAC) to amiodarone may mitigate inflammation and oxidative stress, preventing postoperative atrial fibrillation (POAF). NAC, reported to reduce cardiac surgery POAF, has not been tested in major thoracic surgery. Methods: Patients at high risk for POAF (BNP≥25pg/ml, male, age≥75, or history of AF) who underwent major thoracic surgery (n=154) were randomized to amiodarone + NAC (n=78) or amiodarone + placebo (n=76). Begun on arrival to the PACU were amiodarone 150 mg iv then 1 g/24 h iv x 48 h, and NAC or placebo bolus 50 mg/kg iv then 50 mg/kg/24 h iv x 48 h. The primary endpoint was sustained AF &gt;30 s by telemetry (first 72 h) or symptoms within 7 days of surgery; patients with the primary endpoint underwent home ECG monitoring. Secondary endpoints were AF up to 1-year post discharge and systemic markers of inflammation. Results: Baseline characteristics were similar between arms (Table). POAF occurred in 15/78 NAC patients (19%) and 13/76 placebo patients (17%) (p=0.8). The trial was stopped at the interim analysis for futility. Regardless of treatment, of 28 patients with POAF, 3/28 (11%) were discharged in AF, and 1/28 (4%) met the primary endpoint after discharge. At 1-year, 7/28 patients with POAF (25%) had recurrent episodes of AF, and 1 developed persistent AF—none developed stroke. Inflammatory markers were similar between treatment arms; however, regardless of NAC, on postoperative day 2, patients with POAF (n=28) had higher CRP (p=0.008) and IL-6 (p=0.001) than patients without POAF (n=126). Conclusions: Compared to amiodarone alone, NAC + amiodarone did not reduce the incidence of POAF nor markers of inflammation early after major thoracic surgery. Recurrent AF episodes are common among patients with POAF within 1-year of surgery.
Abstract 16793: Smad7 Induction in Activated Infarct Myofibroblasts Protects From Adverse Remodeling by Restraining TGF-beta-Mediated and Receptor Tyrosine Kinase Signaling
Authors: Claudio D Humeres, Arti V Shinde, Anis Hanna, Simon Conway, Nikolaos G Frangogiannis
Journal: Circulation (2020)

Cardiac repair is dependent on myofibroblast TGF-b/Smad3 signaling and subsequent formation of an organized scar. However, to prevent prolonged activation and fibrosis, TGFβ effects are tightly regulated through induction of suppressive signals, such as the inhibitory Smads, that restrain TGFβ cascades. We hypothesized that the inhibitory Smad7 may be induced in infarct myofibroblasts, protecting from adverse remodeling and fibrosis. Moreover, we dissected the molecular signals modulated by Smad7. Smad7 is markedly induced in infarct myofibroblasts through a TGFβ/Smad3 pathway. To investigate the role of endogenous Smad7 in post-infarction remodeling, we generated mice with myofibroblast-specific Smad7 loss (MFS7KO). Following non-reperfused infarction, MFS7KO mice had increased late mortality that was not due to rupture, but was associated with worse heart failure. Surviving MFS7KO mice had accentuated adverse remodeling, worse systolic/diastolic dysfunction and increased collagen deposition in the infarct border zone, in comparison to Smad7 fl/fl animals. In isolated cardiac fibroblasts, Smad7 overexpression attenuated myofibroblast conversion and profibrotic gene expression, whereas Smad7 knockdown promoted matrix synthesis. In Smad7 KO fibroblasts, overactive fibrogenic activity was associated with enhanced Smad2/3, Erk and Akt signaling, but comparable TβRI/TβRII phosphorylation, suggesting that Smad7 acts downstream of the TGFβ receptors. To dissect the mechanisms for Smad7 actions, we compared the transcriptome of Smad7 KO and WT fibroblasts, in presence/absence of TGFβ. Surprisingly, Smad7 loss had more prominent effects on receptor tyrosine kinase (RTK) cascades than on TGFβ-inducible genes. An RTK protein array identified Erbbs as targets of Smad7 in fibroblasts. Western blot showed that Smad7 restrains Erbb1 and Erbb2 signaling through effects independent of TGFβ. In conclusion, Smad7 induction in infarct myofibroblasts restrains fibrosis, by inhibiting Smad2/3, Erk and Akt signaling via actions downstream of TβRs, and through TGFβ-independent interactions with Erbb1/2. Protective effects of Smad7 in cardiac remodeling may have important therapeutic implications for heart failure patients.
No pain no gain? A conversation on Olympians’ long-term health
Authors: Mike Miller, Debbie Palmer, Jackie L Whittaker, Rebecca Pike, Patrick Schamasch, Malav Shroff, Joël Bouzou
Journal: British Journal of Sports Medicine (2020)

Willie Banks OLY is smiling, he usually is. Olympian, former world record holder and world champion. Inventor of the now ubiquitous track and field competitor overhead hand clap. Successful businessman and international sports leader. Life has been good thanks to elite-level sport. There’s just one snag, Willie has osteoarthritis in his knees and hips. He is in constant pain and attributes his osteoarthritis to past sporting injuries. Willie is not alone. Olympians and former elite athletes often link their past sporting injuries to their current musculoskeletal pain.

There are many benefits to a life devoted to elite sport, with numerous studies reporting the positive effects of sport including a lower risk of morbidity, better self-reported health in later life and higher quality of life.1–4 Despite this, major injuries including anterior cruciate ligament tears and substantial meniscal tears can contribute to radiographic and symptomatic osteoarthritis,5–8 and the risk of osteoarthritis in elite athletes may be higher than that in the general population.4

This reality raises questions. Is enough being done to educate and support athletes and their entourages so they can minimise the long-term …