tbuckley/cabot-search huggingface dataset:
Abstract 13697: Predictors of Prolonged Hospitalization (&gt;48 Hours) and In-Hospital Mortality Among the Patients Admitted With Acute Pulmonary Embolism
Authors: Parth V Desai, Tauseef Akhtar, Axi Patel, Parth Shah, Sovik De Sirkar, Kevin Walsh, Nicolas Krepostman, Matthew Collins, Jawed Fareed, Amir Darki
Journal: Circulation (2021)

Introduction: Prolonged hospitalization leads to worse outcomes in patients admitted with acute pulmonary embolism (PE). However, there is a scarcity of data regarding the factors predisposing to prolonged hospitalization in such patients. Hypothesis: We aimed to identify the factors associated with the prolonged hospitalization and in-hospital mortality among patients admitted with acute PE. Methods: We identified all adults admitted with the primary diagnosis of acute PE from the National Inpatient Sample database (2017). We divided all the admissions into three cohorts based on their hospital length of stay (LOS) — short (sLOS) within 48 hours, medium (mLOS) 3-5 days, and extended (eLOS) &gt;5 days. More than 48 hours of stay was considered prolonged hospitalization. Variables related to patient and hospital-related characteristics were analyzed using logistic regression. Results: A total of 1,87,770 patients (71,215 with sLOS, 72,755 with mLOS, and 43,800 with eLOS) with mean age of 60, 64 and 65 years respectively (p&lt;0.001) were included in the study. Cohorts with mLOS and eLOS had a higher prevalence of females (53% both vs 49%, p&lt;0.001). In multivariate analysis, patients with increasing age, non-white race, tobacco smoking, obesity, associated upper limb and lower limb deep vein thrombosis (DVT), insulin-dependent diabetes, systemic steroids use, recent falls, dementia, and prior chronic respiratory diseases were found to be associated with prolonged hospitalization. Similar factors were also the independent predictors of in-hospital mortality. Interestingly, in-hospital mortality was higher among sLOS (3.8%) and eLOS (4%) compared to mLOS (1.6%). Conclusions: Our study identifies factors independently associated with prolonged hospitalization and in-hospital mortality among patients admitted with acute PE. Knowledge of these factors could aid in treatment strategies and discharge planning.
Abstract 16720: Exercise-Stimulated Catecholamine Release Enhances Resolution of Acute Inflammation
Authors: Jing-Juan Zheng, Ernesto Pena Calderin, Bradford G Hill, Aruni Bhatnagar, Jason Hellmann
Journal: Circulation (2018)

The mechanisms by which regular exercise prevents the development and progression of chronic inflammatory diseases are largely unknown. We find that exercise (Exe) enhances resolution of acute inflammation by promoting macrophage (MФ) phagocytosis and by augmenting resolvin D1 (RvD1) levels. When compared with sedentary controls (Sed), mice adapted to a 4-week treadmill exercise regimen displayed 1.48-fold higher MФ phagocytotic activity, enhanced RvD1 levels (Sed 28.08±1.5 vs Exe 48.01±8.6 pg/mL, n=6), and earlier neutrophilic clearance (ΔR i ~7 h) during peritonitis. Peritonitis cell extracts from exercise-adapted mice showed elevated expression of Alox15 (48 h: Sed 0.97±0.15 vs Exe 1.5±0.16 relative expression, n=8-9), Alox5 (48 h: Sed 0.77±0.15 vs Exe 1.7±0.27 relative expression, n=4-5), and RvD1 levels (48 h: 29.0±2.1 vs 52.6±8.9 pg/mL, n=5). Because exercise stimulates epinephrine (Epi) release, which has immunomodulatory effects, we questioned if Epi exerts pro-resolving actions on macrophages. Epi-treated macrophages displayed higher 15-lipoxygenase 1 expression and RvD1 levels, which were prevented by incubation with the α1 adrenergic receptor (AR-α1) blocker, Prazosin (Praz). During zymosan-induced peritonitis, Praz abrogated exercise-enhanced neutrophilic clearance (48 h: Exe+Veh 2.07±0.41 vs Exe+Praz 5.2±1.04 x10 6 PMN, n=5), MФ phagocytosis (Exe+Veh 33463.0±2174.0 vs Exe+Praz 8303.0±2748.0 MFI, n=5-7), and RvD1 biosynthesis (Exe+Veh 211.0±55.4 vs Exe+Praz 81.79±11.8 pg/mL, n=6). These results suggest that exercise-stimulated Epi release enhances resolution of acute inflammation in an AR-α1 dependent manner. These findings provide new mechanistic insights into the pro-resolving effects of exercise and may lead to the identification of novel pathways to stimulate resolution biology.
Abstract 16908: Valve Calcium Severity is Unrelated to Diet in Severe Aortic Stenosis
Authors: Run Du, Mathew Williams, Zachary Taylor, Zhen-Gang Zhao, Cezar Staniloae, Muhamed Saric, Illya Pushkar, Peter Neuburger, Michael Querijero, Alan Vainrib, Kazuhiro Hisamoto, Nicholas Amoroso, Tara Collins, Emily Clark, Danielle Sin, Binita Shah, Hanah Lee, Samantha Vidal, Daniel Bamira, Ricardo Benenstein, Hasan Jilaihawi
Journal: Circulation (2018)

Introduction: Diet and hyperlipidemia are correlated to coronary atherosclerosis, whose progression may be modulated by statin therapy. Aortic stenosis and calcification are atherosclerotic processes but they are not influenced by statin therapy. Limited data is available on the influence or correlates of diet on aortic valve calcification. Hypothesis: We hypothesized that diet may be related to aortic valve calcification (AVC) on computed tomography (CT). Methods: Consecutive patients with severe or critical aortic stenosis (AS) were evaluated in a busy Heart Valve Clinic and underwent both detailed dietary evaluation with a rate your plate (RYP) questionnaire and a high resolution CT as part of their work-up for valvular intervention (medical therapy, surgical or transcatheter aortic valve replacement). AVC volume was quantified using a validated method based on a higher threshold of detection from the contrast CT (850 Hounsfield Units, HU-850). Dietary data was separated according to patients in the highest tertile of AVC. Results: A total of 117 patients were evaluated. The upper tertile threshold of AVC was identified as 284.5 mm 3 (figure: examples above and below this threshold are shown). Higher scores on RYP identify heart-healthy choices. There were no differences in the overall total RYP score or percentages of specific heart-healthy dietary choices according to AVC severity (table). Conclusions: AVC severity is unrelated to heart-healthy dietary choices in patients with aortic stenosis.
Abstract 13685: Combined Genetic Defects of Sitosterolemia and Familial Hypercholesterolemia
Authors: Satoru Takase, Hiroyuki Ishiura, Masaki Tanaka, Sachiko Okazaki, Mikio Takanashi, Chengcheng Li, Jingxuan Shi, Yoko Iizuka, Jun Mitsui, Shoji Tsuji, Takashi Kadowaki, Toshimasa Yamauchi, Hiroaki Okazaki
Journal: Circulation (2021)

Background: Familial hypercholesterolemia (FH) is an inherited disorder caused by mutations in the genes in the LDL receptor pathway, including LDLR , PCSK9 , APOB, and ARH . Defective uptake of LDL by the liver increases plasma LDL-cholesterol (LDL-C) levels, leading to an increased risk of coronary heart disease. The differential diagnosis of FH includes sitosterolemia which is a rare autosomal recessive disorder caused by mutations in ABCG5 or ABCG8 . Case presentation: Here we present a rare case of sitosterolemia with a genetic diagnosis of FH. A 64-years-old woman, clinically diagnosed as FH with Achilles tendon thickness (&gt;18 mm on X-ray imaging), had been taking statins only intermittently due to muscle pains. The combinatorial therapy with ezetimibe decreased her plasma LDL-C levels to around 90-250 mg/dL with variable adherence to statins and dietary management. Further addition of a PCSK9 inhibitor (evolocumab) was largely ineffective with plasma LDL-C levels of 90-190 mg/dL. A systemic medical evaluation revealed persistent joint pains of unknown etiology and slightly decreased platelet count. These clinical features led us to suspect sitosterolemia. Biochemical and genetic analyses: Plasma concentration of sitosterol was elevated (16.8 mg/dL). Genetic testing was performed after obtaining informed consent. All procedures were subjected to approval by the human genome, gene analysis research ethics committee of the University of Tokyo. In addition to a heterozygous missense mutation in LDLR (p.Arg115His), a homozygous nonsense mutation in ABCG5 (p.Tyr188Ter) was identified. No rare variants were found in PCSK9 nor ABCG8 . Conclusions: To our knowledge, this is the first case of a combined genetic defect of sitosterolemia and FH. Atypical clinical manifestations such as large fluctuations of LDL-C levels, unresponsiveness to a PCSK9 inhibitor, arthralgia, and a reduced platelet count led to the genetic diagnosis. Our case is informative in the perspective of precision medicine, highlighting the importance of systemic medical evaluation to select patients who will be benefited more from genetic testing as well as the necessity of future drug development for this rare and intractable disease.
Abstract 16923: Oxidative Mitochondrial Dna Damage - A Potential Link Between Insulin Resistance and Heart Failure in Ageing Obese Mice
Authors: Olena M Gorodnya, Jared M McLendon, Lyudmila I Rachek, Sergiy Sukhanov, Larysa V Yuzefovych, Mykhaylo V Ruchko
Journal: Circulation (2018)

Introduction: Obesity and age play a central role in the development of insulin resistance, which is a crucial abnormality driving cardiovascular complications. Chronic diabetes can affect cardiac muscle directly, leading to a decline in cardiac function, known as “diabetic cardiomyopathy”. However, molecular mechanisms underlying the link between insulin resistance and heart failure are not clear. Hypothesis: Here, we hypothesize that oxidative mtDNA damage is a linking mechanism between insulin resistance and heart failure, since it contributes to all main pathways distinctive of both processes. Methods: In the present study we used 15-month old mice of three genotypes with different levels of mtDNA oxidation because of altered expression of DNA repair glycosylase Ogg1, the first enzyme in the base excision repair pathway in mitochondria. Wild type (WT) mice, Ogg1 knock-out (KO) mice and KO mice transgenically overexpressing mitochondria-targeted Ogg1 (KOTG) were fed a high fat diet for 14 weeks and analyzed for mtDNA damage, bioenergetic and cardiac functions, and blood glucose and insulin levels. Results: Our previous results showed that young mice deficient in Ogg1 had increased mtDNA damage, altered mitochondrial respiration and left ventricle hypertrophy, but, despite these abnormalities, their cardiac function remained unchanged. Echocardiography of ageing mice in the present study demonstrated increased left ventricle mass (1.5 fold, p&lt;0.05) and decreased cardiac contractility in KO mice when compared to WT animals (ejection fraction: 54.2±3.1 vs. 71.9±5.2 %, respectively, p&lt;0.05). Compared to hearts from WT mice, KO animals displayed a significant decrease in ATP levels (7.2±0.3 vs. 3.8±0.4 pmole/mcl respectively, p&lt;0.05). These changes in cardiac function and bioenergetics observed in KO mice were accompanied by increase in blood glucose and insulin levels. Interestingly, young (5-month old) KO mice fed a high fat diet also demonstrated increased glucose (KO 256.7±19.9 vs. WT 180.8±22.8 mg/dl, p&lt;0.05) and insulin (5 fold, p&lt;0.05) levels when compared to WT animals. These observations indicate that KO mice fed a high fat diet may develop insulin resistance. All these changes were prevented in KOTG mice, which were not statistically different from WT animals. Conclusions: Our results suggest that oxidative mtDNA damage could be a converging point that links both insulin resistance and heart failure in aging obese mice.
Abstract 16881: Role of Neurohormonal Blockade During Anthracycline Therapy: A Meta-Analysis of 14 Randomized Controlled Trials
Authors: Phoo Pwint Nandar, Phyo Thazin Myint, Khine Mon Swe, Ajay Vallakati
Journal: Circulation (2018)

Introduction: Cardiotoxicity is a well-known dose-limiting adverse effect of anthracyclines. The cardio-protective role of the neurohormonal blockade (beta-blocker and/or renin-angiotensin-aldosterone antagonists) in patients receiving anthracycline chemotherapy has been demonstrated, but not consistently in all studies. We performed a systematic review and meta-analysis to evaluate the efficacy of the neurohormonal blockade (NB) for primary prevention of anthracycline-mediated left ventricular (LV) dysfunction. Method: We searched PubMed and Cochrane databases for all studies comparing the effects of neurohormonal antagonists with placebo on LV ejection fraction (LVEF) in the patients receiving anthracycline chemotherapy. We included randomized controlled trials with a follow-up duration of ≥ 6 months. The primary outcome was the change in left ventricular ejection fraction (ΔLVEF). Random effects model with inverse variance method was used to analyze the outcomes. Exploratory subgroup analysis based on the type of NB was performed. Results: We identified 14 studies (n = 1184) which reported ΔLVEF. Pooled analysis revealed that there was a significantly smaller decline in LVEF (weighted mean difference (WMD), 5.38 (95% CI: 2.52 - 8.23, P =0.0002) in the patients who received prophylactic neurohormonal antagonists compared to placebo. Subgroup analysis showed that both beta-blockers (WMD, 4.26 (91% CI: 1.41-7.11), P=0.003) and renin-angiotensin-aldosterone antagonists (WMD, 6.59 96% CI: 1.40-11.78, P = 0.01) were associated with a smaller decline in LVEF. Conclusion: Prophylactic NB attenuates the development of LV dysfunction in patients receiving anthracycline chemotherapy. Studies evaluating the effect on mortality are still required.
Abstract 16657: Role of Exercise Induced Mitral Regurgitation and Its Prevalence in Functional Limitation of Heart Failure Patients With Preserved Ejection Fraction
Authors: Marta Barletta, Francesco Bandera, Andrea Giammarresi, Valentina Labate, Maurizio Losito, Maria M Caracciolo, Marina Rovida, Marco Guazzi
Journal: Circulation (2018)

Background: Functional limitation in heart failure (HF) patients recognize multiple mechanisms. Exercise-induced mitral regurgitation (Ex-MR) has been extensively studied in HF population with reduced ejection fraction (HFrEF, EF &lt; 40%), as responsible of right ventricle (RV) to pulmonary circulation (PC) uncoupling phenomenon. The relative role of this hemodynamic determinant has not been investigated so far in HF patients with preserved (HFpEF, EF &gt; 50%) and mid-range EF (HFmrEF, EF 40 - 49%). Aim: To describe functional phenotypes and cardiac response to exercise in HF patients, with respect to the development of Ex-MR. Methods: 179 HF patients and 23 controls were tested with cardiopulmonary exercise test (CPET) combined with exercise-echocardiography. Based on current guidelines, we identified 114 HFrEF, 34 HFmrEF and 31 HFpEF, further divided according with the presence of at least moderate (&gt;2+/4+) Ex-MR. Results: Ex-MR rate was 58%, 41% and 42% in HFrEF, HFmrEF and HFpEF, respectively. Ex-MR was associated with echocardiographic signs of RV-PC uncoupling (TAPSE/PASP ratio), particularly enhanced by the exercise in HFpEF patients. HFpEF with Ex-MR showed a distinct phenotype with chronotropic competence and increased peripheral oxygen extraction, compared to Ex-MR - cohort, possible expression of a compensatory mechanism to significant reduction in contractile reverse. The Ex-MR was associated with lower peak VO2 and workload in HFrEF and HFmrEF, while there were no differences related to HFpEF. The presence of Ex-MR significantly compromised also ventilatory efficiency (VE/VCO2) in all HF classes. Conclusion: Ex-MR emerged as a new mechanism of functional limitation in HFpEF, sharing a common pathophysiological basis with other HF patients. The RV-PC uncoupling is the best haemodynamic correlate of Ex-MR.
Abstract 13709: TRPV4 Enhances Ca <sup>2+</sup> Transients and Promotes Arrhythmic Ca <sup>2+</sup> Signaling Following Hypoosmotic Stress and Ischemia-Reperfusion
Authors: Deborah Peana, Timothy Domeier
Journal: Circulation (2021)

Introduction: Transient Receptor Potential Vanilloid 4 (TRPV4) is an osmotically activated Ca 2+ channel which enhances cardiomyocyte Ca 2+ cycling and may contribute to arrhythmic Ca 2+ signals in hypoosmotic stress and Ischemia-Reperfusion (I/R). Hypothesis: TRPV4 overexpression enhances Ca 2+ transient (CaT) amplitude and arrhythmic Ca 2+ events in left ventricular (LV) cardiomyocytes exposed to hypoosmotic stress and Langendorff hearts following I/R. Methods: Mouse LV cardiomyocytes from TRPV4 Overexpressors (OEX) and non-transgenic controls (CTL) were exposed to hypoosmotic stress (250 mOsm, 30min). CaT amplitude (paced 0.5 Hz) and arrhythmic Ca 2+ events (prolonged kinetics, spontaneous CaT, Ca 2+ waves) were monitored via confocal imaging (fluo-4, 100Hz). I/R (45min global ischemia, 30min reperfusion) experiments were conducted in OEX and CTL Langendorff hearts expressing the GCaMP6f Ca 2+ sensor (OEX-GCaMP, CTL-GCaMP). CaT and arrhythmic Ca 2+ signals (Ca 2+ waves, alternans, Ca 2+ overload) were monitored in the LV myocardium. Experiments were conducted in the absence and presence of TRPV4 inhibition by HC067047 (HC, 1uM). Results: Incidence of arrhythmic Ca 2+ signals during minutes 0-15 of hypoosmotic stress was increased in OEX cardiomyocytes vs CTL (78 vs 20%, P&lt;0.05, N=9, 5) and prevented in OEX by HC (11%, P&lt;0.05, N=9). Arrhythmia score was increased in OEX vs CTL (1.3±0.7 vs. 0.1±0.1, P&lt;0.05, N=9, 5) and decreased in OEX by HC (0.2±0.2, P&lt;0.05, N=9). Following hypoosmotic stress, CaT amplitude was elevated in OEX vs CTL (F/F 0 = 3.6±0.4 vs 2.1±0.4, P&lt;0.05, N=7, 4) and this effect in OEX was prevented by HC (F/F 0 =2.4±0.4, P&lt;0.05, N=8). Langendorff OEX-GCaMP hearts subjected to I/R demonstrated increased systolic Ca 2+ (F/F 0 =1.8±0.09 vs 1.3±0.1, P&lt;0.05, N=5, 6) during minutes 10-30 of reperfusion, which was attenuated by HC (F/F 0 =1.4±0.08, P&lt;0.05, N=4). OEX-GCaMP hearts were more likely to demonstrate arrhythmic Ca 2+ signals during minutes 15-30 of reperfusion than CTL-GCaMP (27/487 vs 0/415 cells, p&lt;0.05 N=5, 6) and this effect in OEX-GCaMP was prevented by HC (0/633 cells, p&lt;0.05, N=4). Conclusions: TRPV4 activation enhances Ca 2+ transients and promotes arrhythmic Ca 2+ signals, and may provide a novel anti-arrhythmic target in I/R.
Abstract 16936: Arterial Pulse Pressure and Outcomes in Patients With Heart Failure and Preserved Ejection Fraction
Authors: Syed Z Qamer, Philip H Lam, Helen M Sheriff, Selma Mohammed, Apostolos Tsimploulis, Charles Faselis, Prakash Deedwania, Gregg C Fonarow, Ali Ahmed
Journal: Circulation (2018)

Background: Systolic blood pressure (SBP) is a major determinant of PP. An SBP &lt;120 mmHg is associated with a higher risk of mortality in HFpEF (AHA2016 Abstract 20566). We examined the association of PP with outcomes in patients with HFpEF stratified by SBP of 120 mmHg. Methods: Of the 8462 hospitalized patients with HF and EF ≥50% in the Medicare-linked OPTIMIZE-HF registry, 2859 had SBP &lt;120 mmHg (discharge PP: median 48; 1551 had PP &lt;50 and 1308 had PP 50-100 mmHg). Propensity scores for PP &lt;50 mmHg, estimated for each of the 2859 patients, were used to assemble a cohort of 1058 pairs of patients with PP &lt;50 vs 50-100 mmHg, balanced on 57 baseline characteristics. We repeated the above process in the subset of 5603 patients with SBP ≥120 mmHg (PP median 70 mmHg) and in all 8462 patients (PP median 70 mmHg) assembling matched cohorts of 4402 (PP cutoff 70) and 6218 (PP cutoff 60), respectively. Results: Among the 2116 matched patients with SBP &lt;120 mmHg, 1-year all-cause mortality occurred in 35% and 33% of patients with PP &lt;50 vs 50-100 mmHg, resp. (HR, 1.09; 95% CI, 0.94-1.26; Figure ). There was no association with all-cause or HF readmission. HRs (95% CIs) for 1-year mortality in the matched cohorts of SBP ≥120 mmHg (n=4402) and overall (n=6218) were 1.08 (0.96-1.21; p=0185; Figure ) and 1.21 (1.10-1.32; p&lt;0.001), respectively. Conclusion: In hospitalized patients with HFpEF, a lower PP is associated with worse outcomes, but not when stratified by SBP, suggesting that PP has no association with outcomes independent of SBP.
Abstract 16862: Hypertrophic Cardiomyopathy in Octogenarians: Is Age Just a Number?
Authors: Nikolaos Papoutsidakis, Anna Rodonski, Christina Williams, Irene Scanlon, Carol Brescia, Daniel Jacoby
Journal: Circulation (2018)

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy and is typically diagnosed in youth or early adulthood. The clinical characteristics of hypertrophic cardiomyopathy among the very old have not been described. Methods: This is a single-center, retrospective observational study. We queried the Yale Inherited Cardiomyopathies database, obtaining data on HCM patients that were 80 years or older at time of inclusion (5/1/2018) or time of death. Care was taken to exclude patients with other diagnoses that could mimic the HCM phenotype. Results: Results are presented in Table 1. The majority had non-obstructive disease with apical hypertrophy in a substantial majority. All had echocardiographic diastolic dysfunction with concurrent symptomatic heart failure (NYHA II-IV). LA enlargement was substantial with mean LA ESV index of 53.2+-37.5 ml/m2. Atrial fibrillation was common (50%). High risk features such as SCD, ventricular arrhythmias and extreme hypertrophy were absent from this cohort, although syncope and family history of SCD were reported. Genetic test yield was 33%. Conclusions: Non-obstructive HCM with diastolic dysfunction, symptomatic heart failure, and arrhythmia are common among the very old with HCM. These features may reflect a combination of age related diastolic dysfunction and inherited HCM. Despite excellent survival symptomatic structural heart disease, arrhythmia, and stroke risk was the norm. The male:female ratio &gt;1 usually seen in HCM is reversed, suggesting some degree of survival bias. Genetic testing remains useful in this age category. In summary, although HCM is not incompatible with reaching advanced old age, diastolic dysfunction drives significant HCM related morbidity.