tbuckley/cabot-search huggingface dataset:
Abstract 13892: The Impact of Cardio-Renal Comorbidities on Medical Spend in Patients With Diabetes: A Contemporary Analysis of a Large Accountable Care Organization
Authors: Sadeer Al-Kindi, Ian J Neeland, Justin Coran, Betul Hatipoglu, Mahboob Rahman, Sara Rahmani, Peter Pronovost, Sanjay Rajagopalan
Journal: Circulation (2021)

Introduction: While it is well-known that Type 2 Diabetes (T2D) has a disproportionate impact on healthcare expenditure, the precise extent to which cardiorenal and mental health complications of diabetes in accountable care organizations (ACO) influence cost is not clear. We sought to investigate the association between these factors and medical spend in patients with T2D in a large ACO. Methods: We identified all patients (≥ 18 years) with T2D (defined as HbA1c ≥ 6.5% and by ICD10 codes) within our ACO population and linked their total medical spend (inpatient and ambulatory visits) for the year 2020. We investigated the association between medical spend and medical comorbidities (figure A), body mass index (BMI), glycated hemoglobin (HbA1c), and glomerular filtration rate (GFR). Results: A total of 28,566 patients with T2D were included. Mean age was 65 years, 50% were female, and 20% were Black. Comorbid conditions were common: 88% had hypertension, 33% had CAD, 19% had cerebrovascular disease, 19% had HF, 20% had CKD, 32% had OSA, 34% had anxiety, 10% had depression. Median annual spend was $754 per patient. Comorbidities associated with increased spend are shown in figure A. Patients with cardiorenal comorbidities had 723% increase in medical spend. Medical spend was weakly associated with HbA1c and BMI but increased sharply at GFR &lt;25 ml/min/1.73 m2 (figure c). Patients with cardiorenal comorbidities accounted for 50% of all patients with T2D and 79% of the medical spend in T2D. Conclusions: In a contemporary large ACO population, cardiorenal comorbidities are associated with medical spend. Interventions to promote value in ACOs may need to focus on these high-risk groups.
Abstract 16800: Sarcopenia in Advanced Systolic Heart Failure Patients Receiving Left Ventricular Assist Devices
Authors: Amanda R Vest, Alexandra Coston, Corinne Pellows, Nathan Yuen, Angelo DeNofrio, Michael S Kiernan, David DeNofrio, Gregory S Couper, Edward Saltzman
Journal: Circulation (2018)

Introduction: Sarcopenia is the age-related deterioration in skeletal muscle mass and function, which can be accelerated by chronic comorbidities. The prevalence in advanced systolic heart failure (HF) and impact on HF health status are currently uncertain. Sarcopenia diagnostic criteria from the Foundation for the National Institutes of Health (FNIH) and European Working Group on Sarcopenia in Older People (EWGSOP) have not been applied to HF cohorts. Hypothesis: We hypothesized that at the time of left ventricular assist device (LVAD) implantation systolic HF patients have prevalent sarcopenia, and that sarcopenia is associated with poorer nutritional and HF health status. Methods: We recruited 18 adults with systolic HF ±21 days from LVAD implantation. All underwent whole-body dual X-ray absorptiometry (DXA) to calculate appendicular lean mass (ALM). Subjects also underwent a 3-day food recall, Simplified Nutritional Appetite Questionnaire (SNAQ), Kansas City Cardiomyopathy Questionnaire (KCCQ) for HF health status, handgrip strength and blood testing. Sarcopenia was defined by 2 ALM criteria: FNIH – males &lt;19.75kg, females &lt;15.02kg; EWGSOP – males &lt;7.26kg/m 2 , females &lt;5.5kg/m 2 . Linear regression determined relationships between appendicular lean mass and age, weight, handgrip strength, KCCQ summary score, SNAQ score, 24-hour protein intake, and key blood variables, without/with adjustment for sex and height. Results: Sarcopenia was diagnosed in 5 subjects (28%) by FNIH criteria and an additional 5 (10 total, 56%) by EWGSOP criteria (Figure). There were unadjusted associations between lower appendicular lean mass and lower handgrip strength; higher SNAQ score (higher malnutrition risk); lower sodium; and lower hemoglobin. After adjustment for sex and height, lower lean mass remained associated with lower hemoglobin. Lower appendicular lean mass was also independently associated with higher (more favorable) KCCQ scores. Conclusions: As many as half of advanced systolic HF patients meet standard DXA criteria for sarcopenia. Lower appendicular lean mass is independently associated with lower hemoglobin but does not appear to be associated with poorer HF status.
Abstract 11980: Patients With Esophageal Cancer Show Reduction in Myocardial Function and Reduced Oxygen Consumption During Exercise After Chemo-Radiotherapy
Authors: Mette Marie Astrup M Soendergaard, Marianne Nordsmark, Kirsten Melgaard M Nielsen, Steen H Poulsen
Journal: Circulation (2021)

Introduction: Chemo-radiotherapy (CRT) may induce myocardial dysfunction, congestive heart failure and impaired physical performance in patients with esophageal cancer (EC). We aimed to investigate left ventricular function at rest and at peak exercise using echocardiography (ECHO) before and after completed CRT. Material and Methods: We enrolled 47 EC patients, referred to curative CRT, (41.4-50 Gy in 23-28 fractions and carboplatin, paclitaxel) followed by surgery (nCRT), n=38 or CRT, n=9. Evaluation included myocardial function, physical performance, cardiac biomarkers, electrocardiogram, ECHO at rest and during stress, and by cardiopulmonary exercise test before and post CRT. The primary endpoint was changes in LV global longitudinal strain (GLS). Secondary endpoints were LVEF, LV diastolic function, LVEF and GLS at peak exercise and maximal oxygen consumption. Results: Median age was 67 years, 94% males. The median time to post CRT follow-up was 1 day (IQR 0,6). There was a significant drop in LVEF and GLS at rest 56.7 % vs. 53.8% and 17.6 % vs. 16.4%, respectively (p=0.03; p=0.004). Ten patients had an absolute fall of at least 5% in LVEF and 2.5% in GLS. Signs of LV diastolic dysfunction increased from 13% to 21%, p=ns. Peak VO2 and maximal work capacity significantly decreased 21.2 vs. 18.8 and 5.9 vs. 5.4 respectively (p =0.000 and p=0.000). We found a weak correlation between change in GLS at peak exercise and fall in VO2 max (r=0.369 p=0.018). Conclusion: Left ventricular function and physical performance decreased in patients with EC after completed CRT. The decrease of peak V02 performance was only weakly significant related to the changes of peak LV function which indicates that other factors are involved in the decline of the physical performance after CRT. Keywords Esophageal cancer, chemoradiotherapy, cardiac function, working capacity, cardiotoxicity.
Abstract 16692: Clinical Outcomes of Ambulatory Heart Failure Patients Managed With an Intra-Aortic Balloon Pump Prior to Left Ventricular Assist Device Implantation
Authors: Bradley Ternus, Atta Behfar, John Schirger, Simon Maltais, Gregory Barsness, John Stulak, Jacob Jentzer
Journal: Circulation (2018)

Introduction: Patients at increased risk of complications following LVAD placement are admitted to the hospital for hemodynamic optimization prior to LVAD implantation, which can include adjustment of medical therapy and/or placement of an IABP. Hypothesis: Prior to LVAD placement patients treated with an IABP during hemodynamic optimization will have similar outcomes despite worse baseline characteristics compared with patients treated medically. Methods: This single-center study included 199 non-inotrope dependent patients who underwent durable LVAD implantation between January 1 st , 2007 and April 10 th 2017. Hemodynamic data was collected retrospectively. Patients who received an IABP were compared to those who did not. Stage 2 or 3 acute kidney injury, right ventricular failure, and 30 day mortality was compared between patients with and without and IABP. Results: The mean age was 62.7 and 82.9% were male; 72 (36.2%) received an IABP. Baseline characteristics between groups were similar. Patients treated with an IABP had worse INTERMACS profiles and worse baseline hemodynamic parameters. The incidence of the primary composite endpoint was similar between patients who had an IABP and those who did not (23.6% vs 19.7%; p=0.517), as were each of the individual endpoints: stage 2 or 3 acute kidney injury (18.1% vs 14.2%; p=0.472), right ventricular failure (13.9% vs 13.4%; p=0.796), and 30 day mortality (6.9 % vs 3.2%; p=0.226). Patients treated with an IABP had greater relative reductions in mean right atrial pressure (-24.1% vs -5.9%; p=0.044), pulmonary artery systolic (-11.7% vs +3.3%; p=&lt;0.001), diastolic (-17.0% vs +12.0%; p=0.015), and mean pressures (-15.2% vs 0.5%; p=&lt;0.001). Conclusions: Despite worse hemodynamic parameters and INTERMACS profile at baseline, ambulatory heart failure patients who received an IABP prior to LVAD implantation did not have an increased incident of stage 2 or 3 acute kidney injury, right ventricular failure, or 30 day mortality, and had more favorable reductions in right atrial and pulmonary artery pressures. These results suggest that the use of the IABP prior to LVAD implantation in non-inotrope dependent patients with poor baseline hemodynamics may mitigate the risk of postoperative complications.
Abstract 13995: Proarrhythmic Electromechanical Heterogeneities in Patients With <i>KCNJ2</i> Mutations
Authors: Peter M Deissler, Job Stoks, Bianca van Rees, Raphaela Lewetag, Pieter Koopman, Suzanne Gommers, Robert J Holtackers, Godelieve R Claes, Matthijs J Cluitmans, Robert Geukens, Frank R Heinzel, Katja E Odening, Paul G Volders, Rachel Ter Bekke
Journal: Circulation (2021)

Introduction: Loss-of-function mutations of the KCNJ2 gene encoding the inward-rectifier potassium channel, I K1 , are associated with QT prolongation, prominent U waves, abnormal impulse formation and ventricular tachycardia (VT), besides non-cardiac manifestations. The electromechanical consequences of genetic I K1 dysfunction are unknown. Hypothesis: We hypothesize that I K1 dysfunction leads to increased electrical and mechanical dispersion and electromechanical (EMW) negativity. Dynamic heterogeneity of these functional parameters may conspire to arrhythmia. Methods: High-resolution mapping using ECG imaging, speckle-tracking echocardiography and/or tissue-phase mapping CMR were performed in genotyped KCNJ2 -mutation carriers, besides standard 12-lead and ambulatory recording. Results: Five patients (44±13 years; 2 females) were included; KCNJ2 p.(Val93Ile), p.(Arg218Gln), p.(Thr75Arg), p.(Lys49Arg), p.(Gly144Ala). Three had experienced polymorphic VT/VF. Multifocal ventricular ectopic burden averaged 13%. Mean QTc/QTUc were 446±42/610±78 ms, with U-waves of 149±18 ms and 0.087±0.045 mV. ECG-imaging revealed increased epicardial recovery time gradients (168±58 ms/cm), with LV- and RV-contractile heterogeneities by strain: Delta contraction duration (CD) LV 213±77 ms, standard deviation (SD) 58±14 ms; RV Delta CD 30±22 ms, SD 13±9 ms. Abnormal postsystolic shortenings (Fig.), prolonged isovolumic relaxation times (103±25 ms) and reduced diastolic peak velocities (-7.2±1.7 cm/s) indicated impaired early relaxation. The EMW was -51±35 ms with more pronounced negativity in symptomatic patients (-74 vs. -17 ms). Conclusions: Genetic I K1 dysfunction underlies nonuniform mechanical heterogeneities in contraction and relaxation, besides repolarization and resting membrane-potential instability. Significant EMW negativity further promotes ventricular ectopy, potentially precipitating VT.
Abstract 13996: Retention of the NLRP3 Inflammasome-Primed Neutrophils in the Bone Marrow is Essential for Myocardial Infarction-Induced Granulopoiesis
Authors: Gopalkrishna Sreejit, Sunil Nooti, Robert M Jaggers, Baskaran Athmanathan, Ki Ho H Park, Annas Al-Sharea, Jillian Johnson, Albert Dahdah, Man KS Lee, Jianjie Ma, Andrew Murphy, Prabhakara R Nagareddy
Journal: Circulation (2021)

Background: Excessive infiltration of neutrophils to the ischemic heart after an acute myocardial infarction (MI) is mediated in-part by the S100A8/A9-NLRP3-IL-1β signaling axis in neutrophils. Despite upregulation of NLRP3 inflammasome signaling components in neutrophils, the serum levels of IL-1β, was not impacted by MI suggesting that IL-1β is not released systemically. We hypothesize that IL-1β is released locally within the bone marrow (BM) by inflammasome-primed and reverse-migrating neutrophils. Methods: Using parabiosis techniques, we first characterized the migration patterns of different blood cell types across the parabiotic barrier. We next induced MI in one of the parabiotic mice and examined the ability of injury-exposed neutrophils to permeate the parabiotic barrier and induce granulopoiesis in non-infarcted parabionts. Finally, we studied the molecular mechanisms that govern reverse migration and retention of primed neutrophils, IL-1β secretion and granulopoiesis. Cardiac function was assessed by echocardiography. Results: MI promotes granulopoiesis in the BM and introducing a time-dependent parabiotic barrier to the free movement of neutrophils inhibited granulopoiesis in the non-infarcted parabionts. MI also promotes greater accumulation/ retention of inflammasome-primed neutrophils in the BM in a neutrophil CXCR4 (C-X-C-motif chemokine receptor 4) and serum S100A8/A9 dependent manner. In the BM, the primed neutrophils secrete IL-1β through formation of gasdermin D pores and, promote granulopoiesis. Strategies aimed at inhibition of neutrophil homing or release of IL-1β in the BM markedly suppressed MI-induced granulopoiesis and, improved cardiac function. Conclusions: Our data reveals a new paradigm of how circulatory cells can deliver signaling molecules (e.g., IL-1β) directly to the site of action rather than through systemic release. The absolute requirement of signal-2 in the BM for IL-1β release is consistent with our model where neutrophils undergo programming in the infarcted heart and inertly return to the sites of production (i.e., BM) with cytokine cargo (i.e., IL-1β) to regulate granulopoiesis. We suggest that this pathway may exist to limit the off-target effects of systemic IL-1β release.
Abstract 16770: Aortic Stiffness is Negatively Associated With Physical Activity in Children With Congenital Heart Disease
Authors: Jimmy Lopez, Christine Voss, Nicole M Hemphill, Mimi Kuan, Ana Lucia Pozas, Kevin C Harris
Journal: Circulation (2018)

Introduction: Aortic stiffness is an important marker of cardiovascular risk and is increased in children with repaired congenital heart disease (CHD). We have observed and reported on this in children with Tetralogy of Fallot (TOF), Coarctation of the Aorta (CoA), Transposition of the Great Arteries (TGA) and Fontan circulation (FON). Physical activity (PA) is a key determinant of optimal vascular health in children. In children with CHD, we know little about the interaction between PA and aortic stiffness. Hypothesis: There is an inverse association between PA and aortic stiffness in children with TOF, CoA, TGA and FON. Methods: We recruited children aged 9-16 years old with TOF, CoA, TGA and FON during routine clinic visits. PA was objectively assessed using an ActiGraph accelerometer over the right hip during waking hours for 7 consecutive days. Daily minutes of moderate-to-vigorous PA and vigorous PA were averaged over at least 3 valid measurement days, using Evenson cut-points. We measured aortic pulse-wave-velocity (PWV) using standard echocardiographic technique. We calculated PWV (cm/s) by dividing the length of the aortic arch by the transit time from the ascending to descending aorta averaged across 6 consecutive cardiac cycles. Nonparametric statistical tests were used to compare aortic PWV and PA data (p&lt;0.05). Results: Participants (n=68, 60% male) were 12.6 ± 2.3 years old (n=18 TOF, n=20 CoA, n=12 TGA, n=18 FON). Median daily moderate-to-vigorous PA was 45 (IQR: 34-64) minutes/day and vigorous PA was 11 (6-19) minutes/day. Median aortic PWV was 545 cm/s (409-710), which was significantly higher than for children without CHD (~360 cm/s, p&lt;0.001). Lower aortic PWV values were related to higher levels of PA in terms of moderate-to-vigorous PA and vigorous PA (rho=-0.336, p=0.005 and rho=-0.323, p=0.007 respectively). Conclusions: In children with TOF, CoA, TGA and FON, higher levels of PA are associated with better vascular function as measured by aortic PWV. Aortic PWV is elevated in these groups compared to healthy children. The association between PA and vascular function in children with CHD supports the need for care providers to focus on routinely promoting PA in this at risk population.
Abstract 16732: Differential Association of Various Cardiac Hemodynamic Parameters With Renal Dysfunction in End-Stage Heart Failure Patients
Authors: Inga M Melvinsdottir, Timothy M Hess, Ravi Dhingra
Journal: Circulation (2018)

Introduction: Decreased cardiac output is often thought to be the main determinant of renal dysfunction in patients with heart failure. However, large cohort studies are lacking to show these correlations in patients with end stage heart failure. Methods: We selected all adult patients between 2007-2016 who were listed for heart transplant (n=11,030) after excluding those on life support, inotropes, nitric oxide, total artificial heart, percutaneous mechanical or ECMO support, dialysis dependent, biventricular or only right ventricular assist device support and with prior heart or kidney transplant using the United Network for Organ Sharing database. We evaluated associations between renal function and three hemodynamic parameters: 1) cardiac index (CI), 2) mean pulmonary artery pressure (mPA) and 3) pulmonary vascular resistance (PVR) using robust regression models. Results: Average age of patients was 53.5±12.3 years (23% females) with mean estimated glomerular filtration rate (eGFR) of 71.7±26.2 mL/min/1.73m 2 . Nearly half (49%) of the patients had left ventricular assist devices (LVAD) with mPA pressure of 26.2±9.9 mmHg and average CI of 2.4±0.7. There was an inverse correlation between mPA pressure and eGFR (p&lt;0.001) however no association between CI and eGFR (p=0.853); or between PVR and eGFR (p=0.989). After multivariate adjustment, mPA pressure was inversely correlated with eGFR (p&lt;0.001). Subgroup analysis of individuals with LVADs (N=5,417) showed similar results with significant inverse relations between mPA and eGFR (p= 0.008) and no significant correlation between PVR or CI and eGFR (p&gt;0.2 for both). Analysis restricted to individuals with low CI (&lt; 1.8 L/min/m 2 ) and PVR &lt; 4 Woods Units (n=8376) also showed inverse linear correlation between mPA pressures up to 45 mmHg and eGFR (p&lt;0.001). Conclusions: Among patients with end stage heart failure, higher mPA pressure and not the lower cardiac index are cross-sectionally related to lower eGFR values.
Abstract 13911: Regulation of STAT3 Phosphorylation Through β <sub>IV</sub> -Spectrin Interaction and Its Role in Concentric versus Eccentric Hypertrophy
Authors: Drew Nassal, Shivangi Mohta, Nehal Patel, Xianyao Xu, Mei Han, Peter J Mohler, Thomas J Hund
Journal: Circulation (2021)

Hypertrophic growth is a critical determinant of cardiac function in the development of heart failure. In pressure overload, hypertrophy is divided by early adaptive remodeling defined by concentric growth, while chronic hypertrophy associates with eccentric growth and loss in cardiac output. The mechanisms regulating this transition and the impact each profile has in influencing heart function are largely unknown. Importantly, previous work identified a role for the structural protein β IV -spectrin and its interaction with the transcription factor, STAT3, in coordinating hypertrophic profiles. Specifically, mice expressing truncated β IV -spectrin lacking interaction with the hypertrophic signaling molecule CaMKII ( qv 3J mice) were resistant to β IV -spectrin degradation and presented with sustained concentric hypertrophy and ejection fraction (EF) compared to WT following 6 weeks transaortic constriction (TAC). Alternatively, mutant β IV -spectrin mice ( qv 4J ) lacking the STAT3/β IV -spectrin binding domain had reduced EF and LV dilation, consistent with eccentric remodeling, suggesting STAT3/β IV -spectrin is a key regulator of hypertrophic profiles. To evaluate how STAT3 function was altered, we used the STAT3 activator, lipopolysaccharide, on isolated cardiomyocytes, which identified impaired STAT3 Ser727 phosphorylation in qv 4J myocytes compared to WT. The significance of this phosphorylation site was investigated using STAT3 Ser727 phospho-ablated mice (STAT3-S727A), which resulted in accelerated eccentric hypertrophy and HF in response to TAC. Furthermore, we identified elevated Ser727 phosphorylation in the qv 3J TAC mice, which present with sustained concentric growth, compared to WT mice which transition to eccentric growth. The relationship of STAT3/β IV -spectrin and hypertrophic orientation was further examined by adenoviral overexpression of the hypertrophic driver, MEK1/2, on isolated myocytes. While MEK increased the width of WT myocytes, STAT3-S727A and qv 4J myocytes increased in length. Together, these data identify a novel role for β IV -spectrin in coordinating STAT3 Ser727 phosphorylation to tune specific hypertrophic profiles in response to chronic stress and influencing cardiac function.
Abstract 16794: Early Detection of Myocardial Fibrosis by Electrocardiographic Abnormalities in Sickle Cell Patients
Authors: Eduardo Macias Enriquez, Mark Johnson
Journal: Circulation (2018)

Introduction: Advances in screening and treatment of sickle cell disease (SCD) continue to increase life expectancy of this population. As a result, mortality from cardiopulmonary causes has become the most prevalent cause of death. While the specific etiology of cardiac death remains unclear, multiple studies have shown that diastolic dysfunction and prolonged QT are associated with early mortality in SCD. Recently, the physiopathology of a novel cardiomyopathy with both restrictive and hyperdynamic features was described in the SCD population. In addition, a high incidence of repolarization nonspecific abnormalities has been reported in SCD patients. Although these serve as surrogates for repolarization heterogeneity, because of difficulty in reproducibility and measurability they are rarely considered of clinical significance. Hypothesis: Repolarization abnormalities are the earliest manifestation of microvascular changes and fibrosis in the myocardium of SCD patients. Methods: We performed a retrospective electrocardiographic and echocardiographic analysis of 88 patients from our SCD clinic. We used commercially available QT guard plus (QTgp) software to analyze repolarization heterogeneity parameters, and performed echocardiographic measurements of previously validated diastolic markers. In addition, data from 77 individuals - matched demographically with our SCD population- with structurally normal hearts and with normal ECGs was analyzed with QTgp. Results: Our statistical analysis showed correlation between Left ventricular mass index (LVMI), and mitral E/a ratio with T wave morphology changes (T peak, T offset, t wave morphology dispersion, and QRST vector) (table 1). In addition we found that T wave morphology was significatively different between our healthy controls and our SCD population (table 2). Conclusion: T wave morphology changes could be used as an early marker of diastolic dysfunction and increased LVM in the SCD population.