tbuckley/cabot-search huggingface dataset:
Abstract 14185: Acute Pacing Regimen Strengthens Engineered Human Cardiac Tissue
Authors: Cassady Rupert, Kelly Li, Shannon Cirilli, Xia Li, Stuart Campbell
Journal: Circulation (2021)

Introduction &amp; Hypothesis: Engineered heart tissues (EHTs) formed from human induced pluripotent stem cell (hiPSC)-derived cardiomycoytes are a valuable tool for in vitro testing and new technology provides the ability to mechanically test EHTs multiple times to study their longitudinal behavior. We performed these studies to test the hypothesis that acute electrical stimulation of otherwise unpaced EHTs is sufficient to improve contractile properties. Methods: EHTs were formed from seeding hiPSC-cardiomycoytes and human cardiac fibroblasts on MyoPod™ scaffolds of decellularized adult porcine ventricular myocardium. EHTs were cultured, unpaced, for 3 weeks, and then mechanical testing was performed on a MyoLab™ instrument to obtain the baseline contractile phenotype. Testing was performed at culture length under 1 Hz field stimulation in Tyrode’s solution with 1.6 mM Ca 2+ . After approximately 45 minutes of equilibration, contractile properties were calculated by averaging 10 consecutive contractions. Five EHTs were tested over the course of five days. One EHT was returned to culture, in the same, unpaced conditions and re-tested after 3 days. Results: EHTs formed and beat spontaneously at approximately 1 Hz after three to five days in culture. All tissues followed 1 Hz pacing during mechanical testing. The EHTs tested a single time within a five-day window exhibited consistent contractile properties (figure, left) with time-to-peak (TTP) of 222 ± 8 ms and time to 50% relaxation (RT50) of 133 ± 4 ms. (Mean ± SEM, n=4). The EHT retested after three days exhibited a much higher force of contraction, increasing by 50% of its force on day 0 (figure, right) with a corresponding increase in TTP of 220 to 248 ms and stable RT50 of 145 to 147 ms. Conclusions: Taken together, these data demonstrate a remarkable stability of EHTs tested over the course of 5 days and a surprising increase in contractile force imparted by 2.5 hours of pacing at 1 Hz.
Abstract 14312: Inhibition of the Electron Transport Chain and Inflammasome Pathway Preserve Function in Donor Hearts After Circulatory Death
Authors: Renee M Cholyway, Oluwatoyin E Akande, Qun Chen, Edward J Lesnefsky, Stefano A Toldo, Mohammed Quader
Journal: Circulation (2021)

Introduction: Hearts by donation after circulatory death (DCD) have the potential to increase the number of transplantable hearts. However, the DCD process promotes ischemia and reperfusion injury (IRI). Mitochondrial damage and NLRP3 inflammasome activation contribute to the DCD heart damage. Blockade of electron transport chain (ETC) with the reversible inhibitor amobarbital (AMO) or the NLRP3 inhibitor 16773340 (NLRP3-I) can mitigate IRI. Hypothesis: AMO and/or NLRP3-I given to the DCD hearts at the moment of heterotopic heart transplantation afford lasting protection to the DCD hearts. Methods: We induced the DCD process in anesthetized rats that were intubated and ventilated by paralyzing the animal with vecuronium bromide and removing the ventilatory support. Treatment groups were AMO (1 mM), NLRP3-I, AMO+NLRP3-I, and vehicle (N=8-10/group). The DCD hearts were procured after 25 min of in-body ischemia then flushed with ice-cold cardioplegia solution supplemented or not with the AMO. NLRP3-I was administered orally (100 mg/kg) to the recipient before HTx and once a day. Control beating-heart donors (CBD) were procured without ischemia by giving the cardioplegia. The donor hearts underwent heterotopic transplantation in the abdomen of recipients. After 14 days, the function of the DCD heart was measured using an intraventricular balloon. Results: The developed pressure (DP), the peak -dP/dt, and the rate pressure product (RPP) of DCD hearts were significantly reduced compared to the CBD controls (63±7% vs 99±8%; -851±113 vs -1221±123; 20,729±2,268 vs 11,874±1,987, respectively; all p&lt;0.05). AMO, NLRP3-I, and AMO+NLRP3-I preserved the DCD heart function (all parameters, p&lt;0.03). Double treatment AMO+NLRP3-I trended toward a better improvement without reaching statistical significance over single treatments. Conclusions: Inhibition of ETC with AMO alone or combined with NLRP3 inhibition preserved the function of DCD hearts.
Abstract 13144: <sup>18</sup> F-NaF Positron Emission Tomography Imaging Detects Femoral Artery Microcalcification in Patients With Type 2 Diabetes Mellitus and Macroalbuminuria. An Early Marker for Vascular Disease?
Authors: Melanie Reijrink, Judith K Sluiter, Charlotte A Te Velde-Keyzer, Martin H de Borst, Gijs D Van Praagh, Marcel Greuter, Robert A Pol, Jan-Luuk Hillebrands, Peter R Van Dijk, Klaas Hoogenberg, Douwe J MULDER, Riemer Slart
Journal: Circulation (2021)

Background: Although albuminuria is an established risk factor for progression of kidney disease and cardiovascular outcomes, its association with subclinical arterial disease is unclear. [ 18 F]-sodium fluoride ([ 18 F]NaF) positron emission tomography (PET) imaging allows detailed early visualization of arterial microcalcification. This study aims to compare non-invasive imaging markers of subclinical arterial disease measured by microcalcification, macrocalcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without macroalbuminuria. Methods: Participants without cardiovascular history were age and sex matched in three groups: nonT2DM controls, patients with T2DM without albuminuria (MA-), patients with T2DM with macroalbuminuria (MA+). [ 18 F]NaF activity was scored visually (in the aorta and femoral arteries) and was quantified as background activity (blood pool) corrected mean standardized uptake value of the abdominal aorta, and iliac arteries, expressed as target-to-background ratio (TBR). Arterial macrocalcification was assessed with computed tomography (CT) and arterial stiffness with carotid-femoral pulse wave velocity (PWV). Results: Three groups with comparable estimated Glomerular Filtration Rate were included (n=10 per group); controls 91 [81-104] vs MA- 87 [84-93] vs MA+ 85 [60-103] (median [IQR] mL/min*1.73m 2 ). Femoral [ 18 F]NaF uptake was significantly increased in the MA+ group (228 [100-446] vs 33 [0-93] in MA- (p=0.002) and vs 75 [0-200] in controls (p=0.052)), while other imaging markers were not. PWV was significantly higher in the MA+ group compared with MA- group (11.15 vs 8.86 m/s (p=0.009)) while no differences in pulse pressure were found. The [ 18 F]NaF activity in femoral arteries correlated with PWV (r=0.516, p=0.020) and pulse pressure (r=0.508, p=0.012). Conclusions: This study suggests that the presence of macroalbuminuria in patients with T2DM is an indication of early phased arterial disease prior to the development of irreversible macrocalcification. Although larger [ 18 F]NaF PET studies are needed, these results underline the importance of macroalbuminura in T2DM for detecting subclinical arterial disease at an early potentially reversible stage.
Abstract 13078: Cardiovascular Disease Risk Factors and Incident Myocardial Infarction in Patients on Buprenorphine
Authors: Jordan Munger, Katherine Wilkinson, Andrew Sparks, Insu Koh, Neil Zakai
Journal: Circulation (2021)

Introduction: People treated for opioid use disorder with buprenorphine may have increased cardiovascular disease (CVD) risk despite routinely seeing health care providers. We studied CVD risk factors and incident myocardial infarction (MI) in patients on buprenorphine to assess this population’s need for CVD prevention. Hypothesis: People on buprenorphine have a higher burden of CVD risk factors compared to age and sex matched controls. Methods: All patients with primary care visits in a large health network between 2010-2019 were included. Buprenorphine use was defined as receiving buprenorphine during the study period. Incident hospitalized myocardial infarction (MI) was an internally validated electronic health record derived computable phenotype. Patient characteristics and CVD risk factors were compared between buprenorphine use and non-use cohorts after age and sex matching. The risk of incident MI associated with buprenorphine was estimated with Cox-proportional hazards regression matching for age, sex, and a propensity score (PS). Results: In 61,495 people, 539 (0.88%) were on buprenorphine, of which 52.7% (284/539) were female and the average age was 34.6 ± 12 years. Relative to age and sex-matched controls (n=10,780), buprenorphine users had a higher burden of CVD comorbidities including diabetes (5.4% vs 3.6%), hypertension (15.6% vs 12.6%), chronic kidney disease (1.5% vs 0.5%), peripheral artery disease (0.9% vs 0.4%), and history of MI (1.7% vs 0.6%; Table ). The age and sex-matched adjusted hazard of incident MI for buprenorphine was 1.23 (95% CI: 0.38 – 3.94), decreasing to 0.92 (95% CI: 0.23 – 3.70) after PS matching. Conclusions: People on buprenorphine had a higher burden of CVD risk factors than age and sex-matched controls, and a higher point estimate of incident MI that attenuated after accounting for CVD risk factors. There may be an opportunity to reduce the CVD risk of people on buprenorphine, a population already engaged with health care.
Abstract 13096: The Impact of Left Ventricular Outflow Tract Calcium on Hemodynamics and Clinical Outcomes in Patients Undergoing Transcatheter Aortic Valve Replacement With a Contemporary Self-Expanding Valve
Authors: Giorgio A Medranda, Toby Rogers, Brian C Case, Syed Ali, Cheng Zhang, John Wang, Gaby WEISSMAN, Lowell F Satler, ITSIK Ben-Dor, Ron Waksman
Journal: Circulation (2021)

Introduction: Left ventricular outflow tract (LVOT) calcium remains a challenge for transcatheter aortic valve replacement (TAVR). Initial data suggests that self-expanding transcatheter heart valve (THV) confer a lower risk. Data on contemporary self-expanding THVs are lacking. We report the results of the CoreValve Evolut Pro Prospective Registry (EPROMPT), which sought to evaluate the real-world performance of the CoreValve Evolut PRO THV in a multi-center prospective observational registry. Hypothesis: We hypothesized that the CoreValve Evolut PRO THV would perform well across the entire spectrum of LVOT calcium. Methods: The EPROMPT registry (NCT03423459) examined patients across the entire surgical risk spectrum who underwent TAVR using the CoreValve Evolut PRO/PRO+ THV system. Patients were dichotomized based on the degree of their LVOT calcium (none/mild vs. moderate/severe). Patients were followed with 30-day clinical assessment and echocardiography. Results: Of the 238 patients included, 151 (63.4%) had CT-defined none/mild LVOT calcium and 87 (36.6%) had moderate/severe LVOT calcium prior to TAVR. Device success was numerically lower in patients with moderate/severe LVOT calcium (98.0% vs. 94.3%; p=0.121). Acute annular rupture occurred in two patients, one with mild and one with severe LVOT calcium. Rates of stroke were very low in both cohorts, with a trend towards more stroke in the moderate/severe LVOT calcium cohort (in-hospital: 2.0% vs. 4.6%; p=0.251 and 30-day: 2.1% vs. 4.9%; p=0.244). Patients with none/mild LVOT calcium saw higher rates of PPM implantation in-hospital (21.2% vs. 9.2%; p=0.017) with a trend at 30 days (22.2% vs. 13.4%; p=0.105). At 30 days there was a trend towards higher rates of &gt;mild PVL in patients with moderate/severe LVOT calcium (1.3% vs. 3.4%; p=0.271). Mean gradients were low and similar in both cohorts (in-hospital: 8.6 vs. 8.2mmHg; p=0.663 and 30 day: 7.6 vs. 7.7mmHg; p=0.797). Conclusions: The presence of and degree of LVOT calcium did not significantly impact outcomes using the CoreValve Evolut PRO/PRO+ THV with high device success, excellent clinical outcomes, and hemodynamics.
Abstract 13104: L-carnitine Supplementation Improves Right Ventricular Function in Two Models of Right Ventricular Failure
Authors: Vineet Agrawal, Anna R Hemnes, Nicholas J Shelburne, Niki Fortune, Julio Fuentes, Daniel C Colvin, Marion W Calcutt, Megha H Talati, Emily A Poovey, James West, Evan Brittain
Journal: Circulation (2021)

Introduction: Previous studies have shown that right ventricular (RV) failure in pulmonary arterial hypertension is characterized by diminished fatty acid oxidation and ultimate lipotoxicity due to accumulation of toxic lipid intermediates. Whether or not augmenting fatty acid oxidation can reverse lipotoxic RV failure in PAH is not known. Hypothesis: In this study, we tested the hypothesis that augmentation of fatty acid oxidation through L-carnitine supplementation reverses RV failure in two models of RV failure. Methods: BMPR2 (R899X) mice were allowed to develop PAH for 10 weeks prior to supplementation of L-carnitine or control in their water for 8 weeks. In a second model, wild type C57/BL6 mice underwent pulmonary artery banding and were treated with L-carnitine or control 2 weeks after banding surgery. Finally, L-carnitine supplementation was also tested on H9C2 cardiomyocyte-like cells transfected with mutant BMPR2. Lipid accumulation was measured by Oil Red O or BODIPY stain. Fatty acid-mediated mitochondrial respiration was measured by Oroboros Oxygraph or Seahorse analysis. Results: In vivo , L-carnitine in BMPR2 mice and pulmonary artery banded mice increased RV cardiac output, RV ejection fraction, and mitochondrial respiration of long-chain fatty acids. Hemodynamic improvement in RV cardiac output was confirmed in pulmonary artery banded mice. In vitro , L-carnitine reduced lipid accumulation and increased fatty acid oxidation in BMPR2 mutant H9C2 cells through a Cpt1-dependent mechanism. Conclusions: In summary, augmentation of fatty acid oxidation in right ventricular failure through L-carnitine supplementation improves RV function, increases fatty acid oxidation, and decreases lipid accumulation.
Abstract 13035: A Potent Protective Vascular Endothelium Property of <i>Garcinia mangostana</i> L. Extract in High-Risk Framingham Score Patients With Type 2 Diabetes: A Prospective Randomized Control Trial
Authors: Olivia Handayani
Journal: Circulation (2021)

Background: Endothelial dysfunction is the hallmark of vascular complications in cardiovascular disease with type 2 diabetes as the comorbid. Garcinia mangostana L., or mangosteen, has been known as the queen of fruits from Southeast Asia that owns anti-inflammatory and anti-oxidant properties for years. Objective: This study was aimed to evaluate the role of G. mangostana extract as a potent protective vascular endothelium in patients with type 2 diabetes and high-risk Framingham score. Method: This is a prospective, randomized, single blind, placebo-controlled trial in subjects with type 2 DM and high-risk Framingham score. Subjects were randomly divided into two groups: the treatment group of G. mangostana extract, administered 2,175 mg/day in divided dosage for 90 days, and control group receiving placebo. The primary endpoint was the changes in endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) levels. We also evaluated the levels of NO, IL-1, IL-6, TNF-α, fasting blood glucose and HbA1c. Study had been approved by local ethics committee. Statistical analysis was done and p&lt;0.05 was considered significant. Results: From 90 subjects with high-risk Framingham score, there were 49 (54.4%) subjects with type 2 diabetes, which randomly divided into two groups. The treatment group (n=23) received G. mangostana extract and control group (n=26) received placebo. Statistical analysis showed that increase of EPC and decrease of CEC levels were significant in treatment group, compared to control (p=0.000 and p=0.002, respectively). The levels of NO increased significantly (p=0.027) and levels of IL-1, IL-6, TNF-α decreased significantly in comparison to placebo (p=0.003, p=0.002, p=0.000, respectively). Analysis also showed that HbA1c decreased significantly (p=0.002) compared to placebo; however, it was insignificant for fasting blood glucose reduction (p=0.336). Conclusion: Garcinia mangostana L. extract, as an adjuvant therapy, plays a role in improving endothelial dysfunction by significant increase in EPCs and decrease in CECs, in patients with type 2 diabetes and high-risk Framingham score.
Abstract 13030: Hyperglycemia Drives In-Stent Restenosis in STEMI Patients
Authors: Pasquale Mone, Jessica Gambardella, Antonella Pansini, Fabio Minicucci, Ciro Mauro, Gaetano Santulli
Journal: Circulation (2021)

Introduction: Hyperglycemia (HG) has been shown to adversely affect the outcome of ST-elevation myocardial infarction (STEMI). Hypothesis: We hypothesized that HG at hospital admission could increase the risk of in-stent restenosis after primary percutaneous coronary intervention (PCI) for STEMI. Methods: We enrolled consecutive STEMI patients referred to the division of Cardiology of "Antonio Cardarelli" Hospital in Naples, comparing normoglycemic subjects ( NG ), patients without diabetes mellitus but with HG ( HG-non-DM ), and patients with both HG and DM ( HG-DM ). Results: A total of 336 propensity score matched patients were included in the study: 112 NG, 112 HG-non-DM, and 112 HG-DM. At 1-year follow-up, 6.5% of NG patients, 14.0% of HG-non-DM, and 18.5% of HG-DM had been re-hospitalized for restenosis; Kaplan-Meier curves ( p : 0.009) are depicted in the Figure . We then examined these findings applying a multivariate analysis with Cox regression in HG-non-DM patients, observing a significant association with restenosis for glycemia at hospital admission, total and LDL-cholesterol. Conclusions: The present study is the first to evaluate the effects of HG on the risk of restenosis in STEMI patients without DM, comparing the results to both HG-DM and NG subjects. Taken together, our data indicate that HG is associated with adverse outcomes in STEMI patients independently of DM. These findings emphasize the importance of glycemic control in all STEMI patients in order to reduce the risk of complications.
Abstract 13069: Baseline QRS Duration ≫ for &gt;140 msec is Associated With Poor In-Hospital Prognosis of Patients With Acute Myocarditis
Authors: Ayano Yoshida, Takuma Takada, Kentaro Jujo, Eiji Shibahashi, Takanori Kawamoto, Motoko Kametani, Natsuko SATOMI, KAZUHO KAMISHIMA, Takashi Saito, Erina Tomari, Atsushi Honda, Atsushi Takagi, Kyomi Ashihara, Nobuhisa Hagiwara
Journal: Circulation (2021)

Introduction: The clinical manifestation of acute myocarditis (AM) is highly variable, and the mechanisms of this diversity have not been fully elucidated. Hence, it is hard to precisely predict their prognosis, and some cases with AM rapidly progress into cardiogenic shock, resulting in the increased in-hospital mortality. Hypothesis: There are some parameters in the initial presentations to predict the prognosis of patients with AM. Methods: This is a multicenter observational study including hospitalized AM patients between 2007 and 2019. We set the primary endpoint of this study as a composite of in-hospital death from any cause and implantation of ventricular assist devices during the index hospitalization. Results: Of 76 enrolled patients [average age: 42 years; male: 79%; mean left ventricular ejection fraction (LVEF): 41%], 13 patients (17%) developed the composite endpoint, and 8 (11%) died within 10 days after the admission. Patients who experienced the composite endpoint were more likely to be older, and have diabetes, anemia, impaired renal functions, higher creatine kinase-MB, lower LVEF, and longer QRS duration on ECG at admission. In the multivariable logistic regression analysis, QRS duration on ECG at admission was independently associated with the composite endpoint, even after adjusting for confounding factors such as age, sex, and LVEF at admission [OR: 1.31, 95% CI: 1.01-1.72]. The ROC curves for the primary endpoint revealed that the cut-off value of QRS duration at admission were 140 msec (sensitivity: 100%, specificity: 90%, AUC: 0.97). Kaplan-Meier analysis showed that patients with baseline QRS duration &amp;gt; for &gt;140 msec had a significantly higher rate of the primary endpoint than those with QRS duration &lt;140 msec (p&lt;0.001, Figure ). Conclusions: Prolonged QRS duration at admission could predict in-hospital prognosis in patients with AM. We should consider the intensive care and close observation in such a high-risk population with AM.
Abstract 13070: The Probiotic <i>Bifidobacterium breve</i> , Bif195, Supports the Defense Against Aspirin-Induced Gastrointestinal Mucosal Damage
Authors: ANDERS B DAMHOLT, Nina Loen, Sara Engel, Anne Haaber, Anja Wellejus, Filip K Knop
Journal: Circulation (2021)

Introduction: Low-dose aspirin (50-325 mg daily) is widely recommended for the prevention of cardiovascular disease. However, daily use of aspirin is associated with an increased risk of gastrointestinal mucosal damage including gastric and duodenal ulcers. We have recently published data on the ability of the probiotic Bifidobacterium breve , Bif195, to reduce aspirin-induced epithelial damage in the small intestine, as evaluated by capsule endoscopy. However, it remains undetermined whether Bif195 alters aspirin-induced mucosa damage in the gastric ventricle, representing a more aspirin-exposed area and hostile environment for probiotics. Methods: In a 2x4 week double-blinded, placebo-controlled, randomized, crossover clinical trial, 25 healthy men and women were asked to take a daily oral dose of 300 mg aspirin during both intervention periods, and randomized to a sequence of daily oral intake of Bifidobacterium breve , Bif195≥ 10 11 colony forming units) capsules and placebo capsules, separated by a 6 weeks washout period. Participants were subjected to a gastroduodenoscopy immediately before and in the end of each intervention period. All gastroduodenoscopies were performed by the same gastroenterologist. The primary endpoint was change in Lanza score (0-5). Furthermore, mucosal biopsies, luminal fluids and blood samples were collected. Results: Gastrointestinal damage was absent in all subjects at baseline (Lanza score 0). The score was significantly reduced with Bif195 compared to placebo, in the Gastric ventricle. Values after treatment, see the table. Conclusion: Aspirin-induced gastric mucosa damage is significantly ameliorated by intake of Bif195 resulting in a 3 times lower Lanza score compared to placebo, whereas no statistically significant difference was observed in the duodenum. Bif195 may represent a beneficial supplement to continuous aspirin treatment reducing risk of aspirin-induced upper GI mucosa damage and ulcer formation.