tbuckley/cabot-search huggingface dataset:
Abstract 13787: Use of a Novel Cardiac Implantable Electronic Device Digital Care Pathway (TriageHF-Plus) is Associated With a Reduction in All-Cause Unplanned Hospitalizations
Authors: Fozia Z Ahmed, Camilla Sammut-Powell, Paul Callan, Colin Cunnington, Matthew Kahn, Mita Kale, Bart E Gerritse, Hakam Khalidi, David Lanctin, Catherine Leonard, Verla L Laager, Nelson Soken, Glen P Martin, Niall G Campbell, Joanne K Taylor
Journal: Circulation (2021)

Introduction: Heart failure hospitalization (HFH) is common, but it is also potentially preventable. The TriageHF risk score is an implantable cardiac device feature that uses data from up to 9 physiological parameters to classify patients as low, medium, or high risk of HFH in the next 30-days. Aim: To evaluate a remote management heart failure (HF) care pathway (“TriageHF-Plus”) that combines the TriageHF risk score with a structured telephone-based remote clinical patient assessment, by comparing rates of non-elective hospitalizations experienced by patients receiving TriageHF-Plus in a real-world clinical setting to those observed in patients receiving Standard of Care (SoC). Methods: Between Sept 2019 - Sept 2020, 415 patients with TriageHF compatible ICD or CRT devices were prospectively recruited from 3 UK hospitals. Once enrolled, all high risk TriageHF episodes were managed via the TriageHF-Plus pathway; these patients received a structured telephone assessment to assess for both HF and non-HF-related acute issues. Rates of non-elective hospitalizations observed following enrollment in the TriageHF-Plus cohort were compared with those observed in an unselected control cohort of HF patients with CIEDs receiving SoC (n=435) between Jan 2017 - Dec 2018. Results: Patient demographics and hospitalization data are presented in the Table. Nearly all patients in the TriageHF-Plus cohort had HF (91.9%) and the majority (77.8%) had a CRT device. In TriageHF-Plus, there were 135 unplanned all-cause hospitalizations, compared with 358 in SoC; and rates per patient year for all-cause (0.41 vs 0.57, p=0.001), cardiovascular (0.14 vs 0.29, p=0.037) and heart failure (0.02 vs 0.07, p=0.003) hospitalizations were all significantly lower in the TriageHF-Plus cohort. Conclusions: In a population of predominantly HF patients with CIEDs, the TriageHF-Plus pathway reduced rates of unplanned hospitalizations compared with SoC, with the greatest reduction observed in HFH.
Abstract 16820: Clinical Outcomes of Patients Presenting With Acute Heart Failure and Biopsy-Proven Myocarditis at a Major Academic Center
Authors: Ani Nalbandian, Veli K Topkara, Arthur R Garan
Journal: Circulation (2018)

Introduction: Myocarditis is an inflammatory disease of myocardium with heterogeneous clinical presentation. There is limited data on short and long term outcomes of patients with biopsy-proven myocarditis. Methods: We conducted a retrospective study of patients with biopsy-proven myocarditis treated at our institution from 2004-2015 and retrieved demographic, echocardiographic, and outcome data. The primary outcomes were need for mechanical circulatory support (MCS), transplant, or death at 1 year. The cohort was limited to viral or idiopathic myocarditis to exclude clinical variability resulting from other etiologies. Results: In total, 39 patients were identified with a clinical presentation of myocarditis who had a biopsy consistent with this diagnosis. Mean age was 40 ± 15 years and 15 (38.5%) were women. Mean LVEF was 32 ± 17%. Median INTERMACS score was 2 (IQR 1-4). Predominant histologic subtypes were 39% lymphocytic, 21% mixed infiltrate, 8% lymphohistiocytic, 8% mononuclear, 5% eosinophilic, 5% giant cell, 5% histiocytic/eosinophilic and 9% undesignated. Medical treatment included inotropes (64.1%), vasopressors (46.2%), intravenous immunoglobulin (2.6%), steroids (30.8%) or other immunosuppression (15.4%). Twenty (51.3%) patients were treated with MCS which included intra-aortic balloon pump (n=13, 33.3%), percutaneous ventricular assist device (n=2, 5.1%), short term ventricular assist device (n=11, 28.2%, average duration 18 ± 11 days), and veno-arterial extracorporeal membrane oxygenation (n=1, 2.6%); 1 (2.6%) patient required a durable ventricular assist device and was explanted for recovery after 38 days. No patients were transplanted; 6 (15.4%) died, all of whom were treated with MCS and died within 1 month of presentation. Histologic subtypes of those that died were: giant cell (2), lymphocytic (2), mononuclear (1), and mixed infiltrate (1). Cohort survival at 1 year was 84.6% (70% in MCS vs 100% in non-MCS subgroup, p = 0.009). Conclusions: Acute myocarditis is highly variable with regards to clinical presentation and infiltrate cell pattern. Early recognition and appropriate utilization of MCS could improve outcomes. The observed increased mortality with MCS likely reflects sicker substrates needing MCS.
Abstract 16916: Shortening of Pressure Half Time During Exercise as a Predictor for Exercise Capacity in Patients With Bileaflet Mitral Valve Replacement
Authors: Jah Yeon Choi, In-Jeong Cho, Byung-Chul Chang, Sak Lee, Seung Hyun Lee, Chi Young Shim, Hyuk-Jae Chang, Geu-Ru Hong, Jong-Won Ha
Journal: Circulation (2018)

Introduction: In patients with mechanical mitral valve replacement (MVR), effective orifice area is fixed during dynamic exercise. Therefore, pressure half time (PHT) change during exercise might be mainly influence by exercise-induced left ventricular end-diastolic pressure raise. Hypothesis: We hypothesized that shortening of PHT during supine bicycle exercise would predict exercise capacity in patients with bileaflet mechanical MVR. Methods: Patients with isolated bileaflet MVR (n = 40) prospectively underwent symptom-limited supine bicycle exercise testing with Doppler echocardiography. Heart rate (HR), peak and mean transprosthetic gradient, PHT, and systolic pulmonary artery pressure (SPAP) were assessed at different stages of exercise. Changes in PHT during 25W and 50W exercise (ΔPHT-25W and ΔPHT-50W, respectively) were measured. Changes in HR during 25W and 50W exercise (ΔHR-25W and ΔHR-50W, respectively) were calculated. Results: There were significant negative correlations between exercise duration and ΔPHT-25W (r = -0.345, p = 0.032) or ΔPHT-50W (r = -0.369, p = 0.027) ( Figure A and B ). Exercise duration demonstrated independent significant correlation with both ΔPHT-25W (p = 0.018) and ΔPHT-50W (p = 0.006), even after adjusting for age, sex, and ΔHR-25W/50W, respectively. Conclusion: Degree of PHT shortening during 25W and 50W exercise predicted exercise capacity in patients with bileaflet mechanical MVR. More shortened PHT during exercise was associated with low exercise capacity, which might be associated with diastolic dysfunction resulted from exercise-induced left ventricular end-diastolic pressure raise.
Abstract 13893: In an Aortic System of Care Model, Adherence to Guideline Based Care Ii Hampered by Gaps in the Collection, Reporting, and Communication of Echocardiogram Data
Authors: Lucia Gordon, Laney Solsbery, Terreal Rogers, Katy Wirtz, Michelle Scharnott, Gary Myers
Journal: Circulation (2021)

Introduction: Aortic Stenosis (AS) is one of the most common and serious valve diseases, affecting 5% of Americans age 65 or older. Currently, there lacks a national system of care addressing the AS care continuum. The American Heart Association (AHA) has a history of success in systems of care and seeks to apply this experience to create similar for the AS patient through the program, Target: AS. Hypothesis: A key step in an Aortic Stenosis system of care is the identification of the patient’s diagnosis echocardiogram (echo). In some cases, the echo is initially performed at a location other than the tertiary hospital, and a consistent method of reporting the results to valve center does not currently exist. This inconsistency impacts guideline-based care. Methods: Target: AS pilot measures, following current guidelines, were developed with guidance from the AHA’s aortic stenosis scientific advisory group. Hospitals entered 2020 baseline data into the Target: AS data collection tool. Data elements were collected towards the measure: “Percentage of moderate aortic stenosis patients receiving a follow-up echocardiogram during the measurement period that is within 24 months of prior echocardiogram.” Sites reviewed data 24 months prior to the baseline year for the initial echo data. Results: 123 patients in 8 pilot hospitals met inclusion criteria. Overall performance - 53% of patients had a follow-up echo with 24 months. Range was 0% - 65%. All but one patient that failed the measure was due to missing or unavailable prior echo. Engagement with sites through 1:1 interviews, data abstractor calls, and quarterly learning collaboratives revealed that hospitals are not able to find initial echo data in medical records, or that the information is not provided in a discrete manner. Conclusions: The 2020 ACC/AHA Guideline for the Management of Patients with Valvular Heart Disease states that patients diagnosed with moderate aortic stenosis should have a follow-up echo within 24 months of the diagnostic echo. Early data demonstrates that in all but one case, when hospitals cannot meet this guideline, it is due to not having the initial echo results. A hospital cannot monitor its adherence with guideline-based care when it does not have access to necessary data.
Abstract 16601: Evaluation of Vascular Response After Balloon Angioplasty for In-Stent Restenosis Assessed by Optical Frequency Domain Imaging
Authors: Nagataka Yoshihara, Kojiro Miki, Hirokuni Akahori, Takahiro Imanaka, Kenji Kawai, Koji Yanaka, Takamasa Tanaka, Tohru Masuyama, Masaharu Ishihara
Journal: Circulation (2018)

Background and aim: The optimal balloon angioplasty (BA) procedure for in-stent restenosis (ISR) was not established. The aim of this study was to investigate vascular response after BA in ISR lesions using optimal frequency domain imaging (OFDI). Methods and results: This study consisted of 22 ISR lesions that were treated with BA. OFDI analysis were performed for 10mm longitudinal ISR segment including minimum lumen area before and after BA, furthermore morphology of ISR neointimal tissue and volumetric measurements were assessed. We analyzed at 1mm interval cross-sectional OFDI images of lesions before BA, and at every slices per each lesion, the neointimal tissue was divided into 2 morphologic patterns: homogeneous pattern and non-homogeneous pattern. Then, the neointimal tissue morphological characteristics of each lesion was expressed according to “homogeneous ratio”, defined as the number of homogeneous pattern slices divide by a total of slices. In volumetric OFDI measurements, lumen gain rate was calculated as (lumen volume (LV) after BA - LV before BA) / LV before BA, stent expansion rate as (stent volume (SV) after BA - SV before BA) / SV before BA and neointimal volume (NV) reduction rate as (NV before BA -NV after BA) / NV before BA. There was no correlation between homogeneous ratio and lumen gain ratio. There was positive correlation between homogeneous ratio and stent expansion ratio, and there was negative correlation between homogeneous ratio and neointimal volume reduction ratio (figure). Conclusions: OFDI assessment is useful to understand the vascular response by BA for ISR lesions. The mechanism of lumen gain in BA procedure for ISR lesions with homogeneous tissue is mainly obtained by stent expansion, whereas for lesions with non-homogeneous tissue is by neointimal tissue compression.
Abstract 16650: EDEM3 Modulates the Plasma Triglyceride Level via Its Regulation of LRP1 Expression
Authors: Yu-Xin Xu, Gina Peloso, Taylor H Nagai, Amy Deik, Clary Clish, Dan Rader, Sekar Kathiresan
Journal: Circulation (2018)

Population genetic studies have provided abundant insight about the development of diseases in all kinds, which has been validated to be instrumental to prioritize biological research and molecular targets for therapeutic intervention. Here we show another example of endoplasmic reticulum (ER) - degradation alpha -mannosidase like protein 3 (EDEM3) in this aspect. We first used a population genetic approach to highlight a variant in the coding region of EDEM3 that is significantly associated with lower blood triglyceride level in a cohort with &gt;30,000 individuals worldwide. Our functional analysis show that the deletion of EDEM3 gene induced a strong uptake of very low-density lipoprotein (VLDL), but not LDL, as a result of up-regulated expression of low-density lipoprotein receptor (LDLR) - related protein 1 (LRP1). We found that the deletion of EDEM3 gene increased more mannose-containing glycoproteins on cell surface, but without altering the sensitivity of cells to ER stress. Our pathway analyses demonstrate that the gene deletion up-regulated the pathways for RNA and ER protein processing and transport, while down-regulated the metabolic pathways, which may help to maintain a normal response to ER stress, and facilitate the processing and transport of the mannose-containing glycoproteins including LRP1 to cell surface. Lipid metabolite analyses reveal a cellular accumulation of TG under EDEM3 deficiency, in particular those with shorter carbon-chains, a profile largely opposite to the one of the plasma from individuals carrying the EDEM3 missense mutation, suggesting that the data from our functional analysis are consistent with the phenotype of genetic perturbation of EDEM3. Thus, our study identifies EDEM3 as a regulator of plasma TG, and targeted inhibition of EDEM3 expression may provide opportunity for plasma TG lowering.
Abstract 16901: Utilizing In Silico Pathogenicity Prediction Tools and Heterologous Expression Patch Clamp Studies to Identify Bona Fide Pathogenic <i>KCNH2</i> Variants Among Publically Available Exomes Derived From Subjects Without Evidence for Either Type 2 Long QT Syndrome or Type 1 Short QT Syndrome
Authors: Connor L Mattivi, Dan Ye, David J Tester, Daniel J Clemens, Wei Zhou, John R Giudicessi, Michael J Ackerman
Journal: Circulation (2018)

Introduction: Loss-of-function (LOF) and gain-of-function (GOF) pathogenic variants in the KCNH2 -encoded Kv11.1 potassium channel cause type 2 long QT syndrome(LQT2) and type 1 short QT syndrome (SQT1), respectively. Given the prevalence of KCNH2- mediated heart disease (1 in 8000 for LQT2,1 in 100,000 for SQT1) and the reduced penetrance/variable expressivity seen in LQTS and SQTS, large databases such as the Genome Aggregation Database (gnomAD, n=141,352 individuals) might harbor subjects with unidentified LQT2/SQT1-causative mutations. Objective: To determine which “ultra-rare” KCNH2 missense variants (MVs) in gnomAD are most likely to be LQT2- or SQT1-causative. Methods: A list of gnomAD-derived MVs in KCNH2 was compiled. The frequency of each MV in gnomAD was assessed. Each MV was analyzed by 8 in silico pathogenicity prediction tools. MVs that were seen once in gnomAD and predicted damaging by all 8 tools were considered possible LQT2/SQT1-causative MVs worthy of functional validation via whole-cell patch clamp. Results: Overall, 233/474 (49%) of gnomAD KCNH2 MVs were seen in just 1 of &gt;140,000 subjects. Of these, 2 (0.4%) MVs (S320W, S379Y) were predicted damaging by 8 in silico tools. Both S320W and S379Y localize to the N-terminus of the Kv11.1 potassium channel. There was no significant change in peak or tail current density between heterozygously expressed KCNH2-S320W (n=13, p=NS) and KCNH2-WT (n=13). However, heterozygous KCNH2-S379Y (n=12) produced a marked increase in peak current density across the range -30 mV to +20 mV and shifted the V 1/2 of activation by -17 mV (p &lt; 0.001). Also, tail current density of S379Y channels significantly increased across the range -20 mV to +20 mV and the V 1/2 of deactivation shifted by -26 mV (p &lt; 0.001). Conclusion: With this stringent requirement of ultra-rarity, universal prediction of damaging impact, and functionally abnormal electrophysiological properties, one SQT1-causative pathogenic variant in gnomAD was identified consistent with the predicted frequency of SQTS. The search continues among the remaining 32 ultra-rare MVs in KCNH2 where at least 75% of the in silico tools predicted deleterious impact of the MV to find the 15-20 subjects in gnomAD’s population who ought to have an LQT2-causative MV.
Abstract 16743: Targeting Renin Activity in Heart Failure: Precision Therapy With Aliskiren Improves Systolic Function and Prolongs Survival in Female Experimental Dilated Cardiomyopathy
Authors: Ryan D Sullivan, Radhika M Mehta, Ranjana Tripathi, Inna P Gladysheva, Guy L Reed
Journal: Circulation (2018)

Introduction: Patients with heart failure (HF) are treated according to general therapy guidelines, without precise consideration for the individual’s sex and biomarker profile. Renin activation has been implicated in the pathophysiology of HF progression, but studies of the direct renin inhibitor aliskiren in general HF patients have not shown benefits. Mice with experimental dilated cardiomyopathy (DCM) develop progressive HF with reduced ejection fraction that progresses through all stages (A-D) of human HF. Female DCM mice specifically show an elevation of plasma renin activity with a decline in systolic function, severe HF and enhanced mortality (median survival 103 days). We used aliskiren to determine whether renin activity is critical for HF outcomes. Methods and Results: Untreated female DCM mice were compared to female DCM littermate mice given aliskiren (100 mg/kg orally, drinking water) starting at 50 days, Stage B HF (n=20-27/group). When evaluated at 90-100 days, Stage C-D HF, aliskiren suppressed renin activity to normal levels ( P &lt;0.001) and improved cardiac function (ejection fraction, %: 15±1 vs. 11±1, P &lt;0.05; cardiac output, mL/min: 7.5±0.7 vs. 4.6±0.5, P &lt;0.01) compared to untreated DCM littermates. Aliskiren also reduced the development of systemic edema (extracellular water, g: 0.36±0.06 vs. 1.25±0.35, P &lt;0.0001). Treatment with aliskiren delayed loss of body fat and lean muscle mass consistent with cardiac cachexia and sarcopenia. The strongest predictors of survival were fat mass ( r p =0.61, P &lt;0.0001), free water ( r p =-0.55, P &lt;0.0001), and cardiac output ( r p =0.53, P &lt;0.001). Overall, aliskiren treatment resulted in a 7% improvement in median survival ( P &lt;0.05). Conclusion: In females with experimental DCM, targeted treatment of elevated plasma renin activity with aliskiren slowed the development of edema, decreased cachexia, enhanced systolic function, reduced the progression of HF and prolonged survival. These data suggest that more complete biomarker analysis of HF patients may enhance the precision of HF treatment to better address sex-related and individual differences, in order to improve outcomes.
Abstract 16945: Identification of Peripheral Blood Mononuclear Cell Subpopulations in Chronic Left Ventricular Dysfunction Patients With Improved Functional Outcomes: A Biorepository Evaluation From the CCTRN FOCUS Trial
Authors: Lourdes I Chacon, Micheline M Resende, Amir T Gahremanpour, Emerson C Perin, Luiz C Sampaio, Lem T Moye, James T Willerson, Doris A Taylor
Journal: Circulation (2018)

Background: Although cell therapy could potentially slow or reverse progression of chronic ischemic heart failure (HF), clinical trials of bone marrow-derived mononuclear cells (BM-MNC) have met with minimal success. It is unknown why some patients improve (i.e. improvers) and others do not (i.e. non-improvers). B cell numbers, in fact, have been associated with improvement after acute myocardial infarction (MI). We hypothesized that improvers have a higher percentage of B cells in peripheral blood (PB) vs. non-improvers after study treatment. Methods: We used flow cytometry to evaluate temporal changes in the frequency of PB subpopulations after BM-MNC or placebo therapy in HF patients enrolled in the FOCUS-CCTRN trial. PB was collected at day 0 (baseline) and days 1, 30, 90, and 180 from consented participants. Cohort 1 (n=17) patients, who improved in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (ESV), and maximal oxygen consumption (VO 2 max) during the 6-month course, were compared to patients who declined in the above three outcomes, cohort 2 (n=11). Linear mixed model was used to determine the changes over time in each cell population. The difference between each time point to day 0 was calculated as linear contrast. Results: Cohort 1 had a higher frequency of B cells (CD45+CD19+) at day 0 (15.24±7.55 vs. 8.95±3.49, p=0.002), day 1 (14.67±5.53 vs. 8.78±4.51, p=0.003), day 90 (14.98±6.64 vs. 8.49±4.33, p=0.006) and day 180 (13.44±7.85 vs. 8.07±4.34, p=0.033) and regulatory B cells (CD19+CD11B+) at day 0 (2.06±1.20 vs. 1.09±0.58, p=0.011) and day 90 (2.49±1.50 vs. 1.32±0.62, p=0.016) when compared to cohort 2. Both cohorts had an increase in CD11B+ at day 1 when compared to baseline (91.53±3.43 vs. 93.09±3.69, p=0.020) (92.01±3.63 vs. 94.60±8.70, p=0.005), which remained higher in cohort 2 until day 30 (92.01±3.63 vs. 93.92±1.91, p=0.020). Conclusion: A higher frequency of B cells and subsets was observed in PB of patients who improved independent of treatment. These data support prior findings of the importance of B cells in recovery after MI and suggest an important relationship between the humoral immune system and HF.
Abstract 16974: Experimental Insights Into Transapical Neochordplasty: A Quantitative Examination of Neochord Placement Using an <i>Ex Vivo</i> Left Heart Simulator
Authors: Annabel M Imbrie-Moore, Michael J Paulsen, Jung H Bae, Justin M Farry, Hanjay Wang, Camille E Hironaka, Bryan B Edwards, Akshara D Thakore, Haley J Lucien, Daniela M Deschamps, Rohun Kulkarni, Mark R Cutkosky, Y. J Woo
Journal: Circulation (2018)

Introduction: Neochordoplasty is an important repair technique, though the optimal anchoring position is unknown. While typically anchored at papillary muscles, new percutaneous devices anchor the chordae at or near the ventricular apex, which we hypothesize will result in significantly higher forces on the chordae and neochord. Methods: Porcine mitral valves were dissected (n=3) and mounted in a custom 3D printed left heart simulator generating physiological pressure and flow. Hemodynamic and echocardiographic data were collected, and chordal forces were measured using Fiber Bragg Grating (FBG) strain gauge sensors. Isolated MR was induced by cutting P2 primary chordae resulting in prolapse. Regurgitant valves were then repaired with a PTFE neochord with transapical fixation, followed by papillary fixation for comparison. In both cases, the neochord was anchored to a customized force-sensing post positioned to mimic in vivo placement ( Fig. A ). Results: Hemodynamic and echocardiographic data confirmed that both techniques resulted in elimination of MR in all valves and restoration of physiologic hemodynamics. Peak forces on the chordae and neochord were lower for papillary than the transapical fixation (p=0.04). Force tracings were compiled for each class of chordae at baseline, after prolapse, and after both repair techniques ( Fig. B ). The maximum dF/dt for the neochord suture was 30.6 N/s with the papillary fixation and 51.7 N/s with the transapical fixation. These may translate into increased stress on the mitral valve apparatus. Conclusions: Transapical fixation results in higher peak forces on the chordae and noechord suture as well as an increased rate of loading on the neochord when compared to the papillary muscle fixation and may influence repair durability.