tbuckley/cabot-search huggingface dataset:
Abstract 16684: Cardiovascular Responses of Persons With ABI to Computerized Motor-Cognitive Assessments
Authors: Denise Gobert, Sarah Edmiston
Journal: Circulation (2018)

Introduction: Recent evidence suggests that a traumatic brain injury is associated with a higher risk for cardiovascular pathology and impaired responses to activities of daily living. However, limited standardized testing is available to document cardiovascular responses during motor-cognitive function after acquired brain injury (ABI). Our study aimed to compare cardiovascular responses in persons with and without ABI during motor-cognitive assessments in virtual-reality gaming environments. Hypothesis: We hypothesized that there would be a significant difference in participant effort as defined by cardiovascular response specific to each activity. Methods: 50 participants (M/F = 16/34) age 29.31 (+/-11.667) years with and without ABI (9/41) performed a timed, 4-square stepping task to test dynamic balance (4SST) and the standardized Montreal Cognitive Assessment (MoCA).Testing included polar heart monitoring of participant effort via heart rate (HR) while performing five standardized, virtual-reality games to test motor-cognitive skills. Variables included HR, 4SST time, MoCA score, and computerized Cognitive Scores (ICOG). Descriptive statistics explored group performance using SPSS 24.0 (IBM) and an alpha level of 0.05. Results: results Indicated similar performance in MoCA and ICOG scores (26.78 +/- 2.188, 28.043 +/- 2.230 respectively) but ICOG effort ratings were significantly higher in the ABI group compared to without ABI (2.60 +/- 1.140 vs. 1.60 +/- 1.095 respectively). Also, the ABI group took significantly longer to complete each ICOG activity (34.056 +/- 24.461 vs. 29.964 +/- 25.727 respectively) with significantly delayed reaction times (3.598+/- 1.542 vs. 2.825 +/- 1.630 respectively). Significant relationships occurred between the ICOG activity score and the associated HR (r = - 0.512, p = 0.030) and 4SST and AGE (r = 0.526, p = 0.025). Multiple regression analysis indicated history of concussion, previous night hours of sleep, MoCA scores, gender, and HR significantly explained 61.2% of the ICOG variance (p = 0. 005). Discussion: Results indicate significant differences in cardiovascular responses to motor-cognitive activities however similar performance in MoCA and ICOG scores. There was also a significant difference in effort and reaction time scores. This trend appeared to explain overall ICOG performance as presented by the regression analysis. Conclusions: Preliminary findings warrant further research of cardiovascular responses during specific motor-cognitive tasks common to ADL’s.
Abstract 16883: Ablation of Slc26a6 Protects the Heart From Ischemia/Reperfusion Injuries
Authors: Phung Thai, Lu Ren, Hannah A Ledford, Padmini Sirish, Richard Q Ngo, Valeriy Timofeyev, Yang Li, Xiaotian Zhou, Zhong Jian, Ye Chen-Izu, Nipavan Chiamvimonvat, Xiao-dong Zhang
Journal: Circulation (2018)

Introduction: Ischemic heart disease is the most common type of heart disease, accompanied by a major decline in local myocardial pH, resulting in abnormal cardiac function. However, the mechanisms of pH regulation and the homeostasis of H + neutralizing buffers, such as HCO 3 - and Cl - in cardiomyocytes remain incompletely understood. We have recently identified a key molecule, Slc26a6, in mouse and human hearts, which mediates electrogenic Cl - /HCO 3 - exchange and plays key roles in the regulation of cardiac pH i , excitability and contractility. Because Slc26a6 is an acid loader in cardiomyocytes, we hypothesize that ablation of Slc26a6 may protect the heart from ischemia/reperfusion (I/R) injury. Methods: We generated I/R model using wild type (WT) and Slc26a6 knockout ( Slc26a6 -/- ) mice. Multidisciplinary in vivo and in vitro approaches were used, including echocardiography, electrophysiology, hemodynamic monitoring, electrocardiography (ECG), and histochemistry. In addition, cellular experiments were performed to test the Cl - /HCO 3 - exchange currents, Ca 2+ transient, sarcoplasmic reticulum Ca 2+ load, and sarcomere shortening. Results: ECG recordings were performed during the I/R surgery to monitor the I/R injury. 24 hours after reperfusion, troponin I level was lower in Slc26a6 -/- I/R mice relative to WT I/R mice, suggesting less cardiac injuries in Slc26a6 -/- mice. This was validated 4 weeks after I/R. Slc26a6 -/- I/R mice showed better systolic and diastolic function than WT I/R mice, assessed by echocardiography and hemodynamics monitoring. Moreover, histological analyses revealed lower collagen formation and smaller infarct size in Slc26a6 -/- compared to WT mice. In vitro analyses of sarcomere shortening, Ca 2+ transients, and sarcoplasmic reticulum Ca 2+ load of the cardiomyocytes from infarct zone corroborated the in vivo findings, showing more preserved cellular function in Slc26a6 -/- compared to WT mice. Conclusion: Ablation of Slc26a6 is cardioprotective in a murine model of I/R, which may result from the elevated pH i and the reduction of acidification during I/R. Our findings suggest critical roles of Slc26a6 in I/R injury. Slc26a6 may represent a novel therapeutic target for cardioprotection in ischemia through pH regulation.
Abstract 16811: Concomitant Fetal Heart and Brain Mri in Congenital Heart Disease Mouse Models With Sub-Nyquist Acquisition
Authors: Yijen L Wu, Anthony G Christodoulou, Cecilia Lo
Journal: Circulation (2018)

Introduction: Congenital heart disease (CHD) patients suffer higher incidences of neurocognitive impairment. An unanswered clinical question is whether the poor neurodevelopmental outcome in CHD is driven by hemodynamic perturbations arising from the structural heart defects or primarily driven by patient intrinsic/genetic factors. In order to simultaneously evaluate genetic factors, structural heart defects and brain development in CHD mutant mouse models, we have developed a fast MRI methodology for simultaneously imaging fetal mouse hearts and brains. Methods: The specific challenge for fetal mouse MRI is to overcome motion artifacts arising from multiple fetuses and maternal abdominal and respiratory motion. We performed 4D MRI in utero using a hybrid compressed sensing and low-rank imaging method. The two key features of this fetal MRI approach are (1) the ability to express incoherent fetal and maternal motion with reduced degrees of freedom; and (2) a sub-Nyquist sparse sampling scheme to accelerate acquisition and increase temporal resolution. This allows assessments of anatomical structures and the hemodynamic function and its relationship with the developing fetal brain. Results: 4D MRI was performed in utero of a pregnant female mouse on embryonic day E16.5. Outlier respiratory states were automatically identified and removed before image reconstruction. After reconstruction, the image closest to the median image was automatically extracted for analysis. The boundary of each individual yolk sac is indicated by yellow dotted lines, with embryos numbered from E1 to E8. This isotropic 3D data set can be re-oriented according to each embryo’s body axis. FigA shows the sagittal orientation of embryo #2 to highlight brain structures. FigB shows the coronal view of the embryo #7 to highlight stomach, liver, and both kidneys. Placenta can be clearly seen as well (Fig.C). Conclusion: Our fetal MRI can be used to evaluate congenital heart and brain defects.
Abstract 13713: Short-Term Outcomes of Acute Mitral Regurgitation in Patients With Takotsubo Cardiomyopathy
Authors: Bilal Alqam, Fuad Habash, Zaid Gheith, Srikanth Vallurupalli, Waddah Maskoun
Journal: Circulation (2021)

Introduction: Takotsubo cardiomyopathy (TC) is characterized by significant transient left ventricular dysfunction that is not due to obstructive coronary artery disease. Acute mitral regurgitation (MR) has been described in previous studies as a complication of TC, but short-term outcomes are not well studied. The aim of our study was to investigate the rates and outcomes of patients diagnosed with TC with acute MR in the Veteran Affairs (VA) system. Methods: We performed a retrospective study using chart review for patients diagnosed with TC between 2005 and 2018 in the VA national database. We included patients who met the Mayo Clinic diagnostic criteria for TC. We collected data for demographics, clinical course, and outcomes. Results: 287 patients (70.7% males) were included, Median age was 64 years, 18.8% were known to have coronary artery disease, 34.1% were diabetic and 60.3% had hypertension. 96% of patients had apical variant of TC. Moderate to severe MR was present in 8.7%; of those 48% were either new or significantly worsened MR when compared to previous echocardiograms prior to TC. MR was mostly diagnosed in patients with apical TC (91.7%). There was no significant difference in the rates of diagnosis of new MR in men compared to women (3.4% vs 6% p=0.34). There was also no significant difference in the in-hospital mortality rates between patients with new moderate-severe MR vs no-trivial MR (0% vs 8.7%, p = 0.61). At 30-day follow up there was no significant difference in mortality rates in patients with moderate-severe MR compared to no-trivial MR (9.1% vs 2.5%, p = 0.22). On follow up echo for patients who survived, all patients had resolution of the MR. Conclusions: In patients diagnosed with TC with new moderate-severe MR, there was no significant difference in mortality rates in the hospital or at 30-day follow up.
Abstract 16693: Standalone Quantitative <sup>18</sup> F-NaF Coronary PET Fused With Prior Deep-Inspiration Coronary CT Angiography for Improved Patient Workflow
Authors: Jacek Kwiecinski, Sang-Eun Lee, Damini Dey, Sebastien Cadet, Martin L Lassen, Maurits Jansen, Marc R Dweck, David E Newby, Hyuk-Jae Chang, Mijin Yun, Daniel S Berman, Piotr J Slomka
Journal: Circulation (2018)

Introduction: 18 F-NaF PET holds promise in distinguishing high-risk plaques in patients with coronary artery disease. The current imaging protocol requires a hybrid single-session acquisition of coronary computed tomography angiography (CTA) and PET. This approach does not allow high-risk patient selection for 18 F-NaF imaging based on prior CTA findings. We aimed to determine whether prior deep inspiration CTA fused with a subsequent PET-only scan allows reliable evaluation of coronary 18 F-NaF uptake. Methods: Twenty-five patients (age 65±6 years, 68% males) underwent clinical CTA (CTA1) on a dual-source CT scanner and subsequently combined 18 F-NaF PET/CTA (CTA2) imaging on a hybrid PET/CT scanner within 16 [9,28] days. We fused CTA1 with 18 F-NaF PET (PET) and compared the visual pattern of activity, maximal standard uptake values (SUVmax) and target to background ratio (TBR) measurements on prior-CTA (PET/CTA1) versus hybrid (PET/CTA2) cardiac motion corrected PET images. Results: On PET/CTA2, 118 coronary plaques were identified. Thirty-six coronary segments from 14 (56%) patients had high 18 F-NaF uptake (TBR&gt;1.25), while 82 segments had lesions with 18 F-NaF TBR ≤1.25. Uptake in all lesions was categorized identically on co-registered PET/CTA1. There was no difference in 18 F-NaF uptake between PET/CTA1 and PET/CTA2 (SUVmax: 1.46±0.59 vs. 1.45±0.57, p=0.53; TBR:1.28±0.55 vs. 1.26±0.53, p=0.41). Repeatability of uptake measurements was excellent with intraclass correlation coefficients of 0.98 (95% CI 0.97 to 0.99, p&lt;0.001) and 0.94 (95% CI 0.92 to 0.96, p&lt;0.001) and limits of agreement of ±0.18 and ±0.19 for SUVmax and TBR respectively. Conclusions: Coronary CTA/PET protocol with CTA first followed by PET-only allows for reliable and reproducible quantification of 18 F-NaF coronary uptake. This approach may facilitate selection of high-risk patients for PET-only imaging based on results from prior CTA, providing a practical workflow for clinical application.
Abstract 16981: Prevalence of Primary Severe Hypertriglyceridemia in Olmsted County, Minnesota: A Community-Based Study
Authors: Harigopal Sandhyavenu, Ahmed Pasha, Medhat Farwati, Kent Bailey, Iftikhar Kullo
Journal: Circulation (2018)

Introduction: Severe hypertriglyceridemia (SHTG), defined as plasma triglyceride (TG) level ≥ 500 mg/dl, is a risk factor for cardiovascular disease. In the NHANES dataset (2001 - 2006), the prevalence of SHTG was 1.7%. However, the prevalence of primary SHTG in the community is unknown. We conducted a community-based study to estimate the prevalence of primary SHTG, in Olmsted County, Minnesota. Methods: We used the Rochester Epidemiology Project (REP) records linkage system to identify individuals with TG ≥ 500 mg/dl between 1998-2015. Index date was defined as the first documentation of TG ≥500 mg/dl during the study period. We excluded individuals with mixed hyperlipidemia (TG ≥500 mg/dl and non-high density lipoprotein (HDL) cholesterol ≥190 mg/dl). HTG was defined as secondary in the presence of hypothyroidism, biliary obstruction, nephrotic syndrome, uncontrolled diabetes, pregnancy, liver disease, renal failure, BMI ≥35 and medication use (isotretinoin, tetracyclines, anti-retrovirals). Primary HTG was defined as absence of an identifiable secondary etiology. Characteristics of the primary SHTG individuals were ascertained from the electronic health record. Results: SHTG was identified in 3802 individuals of whom 2511 had mixed hyperlipidemia, 743 had a secondary cause for SHTG and the remaining 548 had primary SHTG. Using the 2015 population census of 151,436 for Olmsted County, the prevalence of SHTG was 2.5%, of secondary SHTG was 0.49% and of primary SHTG was 0.36%. Only half of the primary SHTG group had a diagnosis of dyslipidemia in the electronic health record and 44.3% were on lipid-lowering therapy on index date. Characteristics of individuals with primary SHTG are summarized in Table 1. Conclusions: These data highlight that primary SHTG is relatively common (≈1 in 300, similar to the prevalence of familial hypercholesterolemia), underdiagnosed and undertreated.
Abstract 13725: Comparison of 30-day Readmission After Hospitalization for Heart Failure With Amyloidosis versus Those Without Amyloidosis: Insight From National Readmission Database
Authors: IRIAGBONSE ASEMOTA, Emmanuel Akuna, RAQUEL SOON-SHIONG, LIN LI, CYRA-YOONSUN KANG, SMRITI KHANAL, MUHAMMAD ALMANI, Mahmoud Elbermawy, Bharosa Sharma, PRAJWAL SHRESTHA, DENNIS KUMI
Journal: Circulation (2021)

Introduction: Heart failure is a common presentation in patients with amyloidosis. The aim of this study was to compare the non-elective 30-day readmission rates among patients hospitalized with heart failure (HF) with and without a secondary diagnosis of amyloidosis. Methods: Using the 2018 nationwide readmissions database, we identified patients with a principal discharge diagnosis of heart failure and stratified all cause 30-day readmissions to two groups, those with coexisting amyloidosis and those without amyloidosis. We utilized Chi-square tests to compare baseline characteristics between readmissions for both groups. The mean length of hospital stay (LOS) and total hospital charge (THC) were also compared for both groups using regression analysis. Results: HF failure patients with co-existing amyloidosis had a significantly higher 30-day all-cause readmission rate (22% vs 16.5%, P=0.03), with 4.25 days increase in the unadjusted mean LOS (5.68 vs 9.94 days, P=0.026) compared to their cohorts without amyloidosis. The amyloidosis group were older (68.4 vs 64.7 years, p=0.149), had a higher odd of inpatient mortality (AOR: 2.69, P = 0.144), and accrued a higher THC of $30,525 ($84,549 vs $54,024, P=0.11) in comparison to their non-amyloidosis counterparts however, these were statistically non-significant. Conclusions: Patients admitted with heart failure with amyloidosis had a higher 30-day all cause readmission rate and stayed longer in the hospital in comparison to HF patients without amyloidosis. Early risk stratification and intensive treatment may help reduce unplanned readmission rates among heart failure patients with amyloidosis.
Abstract 16799: Decellularized Cardiac Extracellular Matrix Increases Cardiomyocyte Elongation and Contractility
Authors: Karis R Tang-Quan, Yutao T Xi, Camila T Hochman-Mendez, Luiz C Sampaio, Doris A Taylor
Journal: Circulation (2018)

Background: Cardiomyocyte elongation has been linked to enhanced myofilament organization, which contributes to overall cell contractility and functionality. While tissue scaffolds have been engineered to induce cell elongation using topographical cues, decellularized cardiac extracellular matrix (dECM) bioscaffolds are known to be bioactive and retain native cues for cell organization and regeneration, including the alignment of stem cells. However, the effects of the native extracellular matrix on cardiomyocyte elongation and contractility are still unknown. Hypothesis: We hypothesized that dECM increases elongation and contractility of neonatal rat ventricular cardiomyocytes (NRVCMs) versus engineered collagen constructs, resulting in physiologically-relevant, scalable tissues for cardiovascular tissue engineering. Methods and Results: Adult rat hearts were harvested and perfusion-decellularized through the coronary vasculature under constant pressure. Hearts were sectioned on a vibratome transversally to create 300 μm-thick rings of the left ventricle. Collagen (type 1) rings of the same size as the dECM rings were made by using rat tail collagen (2.0 mg/ml). Ten million NRVCMs were isolated, purified, and injected into the left ventricle of dECM or collagen rings (n=12 each). Cell survival, distribution, elongation, and alignment were evaluated after 14 days by using immunofluorescence and confocal microscopy. The dECM significantly increased nuclear elongation (major to minor axis ratio of 1.585 for cells in dECM vs. 1.37 in collagen, n=6 each, p&lt;0.01). Microscopic contractions were observed in dECM as early as day 3 (n=3). The number of spontaneous contractions of cells in dECM (n=5) was significantly greater than that in collagen (n=3) (p&lt;0.01), as observed by atomic force microscopy. Conclusion: In conclusion, dECM increased cellular elongation and contraction frequency of neonatal rat ventricular cardiomyocytes, suggesting the presence of tissue-specific cues in the extracellular environment of cardiomyocytes is beneficial for tissue function. Studies utilizing human stem-cell derived cardiomyocytes are underway to verify the organizational, functional, and physiologic properties of recellularized dECM.
Abstract 16948: TXLNB is Necessary for Physiological Hypertrophy During Cardiac Aging
Authors: Jared M McLendon, Xiaoming Zhang, Nathan H Witmer, Gabrielle M Abouassaly, Colleen S Stein, Ryan L Boudreau
Journal: Circulation (2018)

Cardiac aging in mice and humans is associated with cardiac hypertrophy, fibrosis, diastolic dysfunction, and a reduced ability to adapt to stress. Recent evidence suggests that cardiac proteostasis - the coordinated regulation of protein synthesis, repair, and degradation mechanisms - is dysregulated during cardiac aging and contributes to cardiac structural and functional deficits, but the underlying molecular mechanisms are unknown. In recent work, we identified beta-taxilin ( TXLNB ) as a cardiac-enriched protein that regulates cardiomyocyte proteostasis. Overexpression of TXLNB in neonatal rat cardiomyocytes increased protein synthesis, decreased ubiquitination, increased proteasome activity, and increased autophagy. In addition, TXLNB -knockout ( TXLNB -KO) mice generated by CRISPR/Cas9 exhibited altered cardiac proteasome activities (Fig. 1A: decreased 26Sβ5 activity (p=0.025, n=8), increased 26Sβ1 activity (p=0.13, n=8), and accumulate ubiquitinated proteins (Fig. 1B). Despite this profound proteasomal insufficiency, TXLNB -KO mice develop normal cardiac structure and function (at 12 weeks of age) and show appropriate hypertrophic responses to pressure overload via transverse aortic constriction. This suggests that TXLNB is not required for cardiac development or cardiac hypertrophy in young mice. We therefore initiated follow-up studies in 3, 6, 10, and 24 week-old mice to evaluate the role of TXLNB in aging-related cardiac hypertrophy. In these mice, there was no significant difference in body weight or tibia length based on genotype; however, between 10-24 months of age, TXLNB -KO mice did not show the typical increase in heart size observed in WT mice (Fig.1C, 10 months, p=0.023, n=7; 24 months, p=0.026, n=3-4). This suggests that TXLNB is necessary for adaptive cardiac remodeling that occurs during aging. Ongoing work will establish if aged TXLNB -KO mice have decreased cardiac function or an impaired adaptation to cardiac stress.
Abstract 16907: Natural Killer T (NKT) Cells Are Protective in Cardiac Arrest and Resuscitation
Authors: Edy Y Kim, Kei Hayashida, Kohei Ikeda, Ji Young Choi, Jing Yu Guo, Aidan M Cullen, Soeun Ngoy, Benjamin Olenchock, Fumito Ichinose, Michael B Brenner
Journal: Circulation (2018)

(Submitted for Cournand and Comroe Award) . Introduction: After out-of-hospital cardiac arrest and cardiopulmonary resuscitation (CA/CPR), mortality rates are 90%, primarily because of neurological dysfunction. However, there are no pharmacological treatments to help neurological function after sudden CA/CPR. The role of the immune system after CA/CPR is unclear and has not been tested as a therapeutic target. Innate T cells are a subset of T cells. We explored the role of innate T cells in CA/CPR because innate T cells are potent master regulators of the early inflammatory response in other diseases, such as infections. Hypothesis: Innate T cells and their antigens are novel therapeutic targets to treat neurological dysfunction after CA/CPR. Methods: Mice were mechanically ventilated and underwent 8 min. of normothermic asystolic cardiac arrest with potassium chloride i.v. Mice were resuscitated with chest compressions and epinephrine i.v. Results: The two major types of innate T cells in mice are Natural Killer T (NKT) cells and gamma-delta T cells. Here, we show that NKT cells improved neurological function and survival after experimental CA/CPR. First, we found that, after CA/CPR, NKT cells recognized the lipid antigen sulfatide, which is abundant in brain myelin. These sulfatide-specific NKT cells trafficked to the brain after CA/CPR. Mice deficient in NKT cells had worsened neuro-inflammation, with increased IFNγ and infiltration of Ly6c+CCR2+ macrophages and neutrophils in the brain after CA/CPR. Deficiency in IFNγ or CCR2 improved neurological function and survival after cardiac arrest. Treatment with the lipid antigen sulfatide after cardiac arrest improved neurological outcomes. Conclusions: This study identifies NKT cells as a key regulator of neuro-inflammation, neurological function and survival after cardiac arrest. We introduce immunomodulatory lipids, such as sulfatide, as a novel treatment class for cardiac arrest.