tbuckley/cabot-search huggingface dataset:
Abstract 13958: A Novel Approach to Quantifying Guideline-Directed Medical Therapy Accounting for Treatment Intensity
Authors: Mirza S Khan, Charles F Sherrod, Philip G Jones, Gregg C Fonarow, Javed Butler, Adam D Devore, Paul S Chan, John A Spertus
Journal: Circulation (2023)

Introduction: Measuring the intensity of guideline-directed medical therapy (GDMT) is foundational for improving care in heart failure (HF). Existing measures either discount dose intensity or use inconsistent weighting. Methods: The primary aims were to create the Kansas City Medical Optimization (KCMO) score, an interpretable GDMT score customizable to individual patients’ treatment eligibility, and to compare KCMO score distributions with the HF Collaboratory (HFC) and modified HFC scores in the CHAMP-HF registry. KCMO is the average of total daily to target dose percentages for eligible GDMT drug classes, reflecting the percent of optimal GDMT prescribed (range 0-100%). The HFC and modified HFC scores transform total daily to target dose percentages into points: 0 if none, 1 if &lt; 50%, 2 if ≥ 50%, or (HFC only) set points for MRA (2) or ARNI (3) if on any dose. In the CHAMP-HF registry, we computed KCMO, HFC (range 0-7), and modified HFC (range 0-100) scores for each patient at baseline and 1-yr change from baseline for the 3 established GDMT therapies at the time (MRA, BB, and ACEI/ARB/ARNI). We compared baseline and change score distributions and the coefficient of variation (CV) across scores. Results: At baseline (n = 4,532), the mean KCMO, HFC, and modified HFC scores were 37.0 (SD 25.0), 3.4 (1.6), and 38.7 (18.3), respectively. Of those with data at yr 1 (n = 4,061), mean change from baseline for the KCMO, HFC, and modified HFC scores were -1.67 (17.7), -0.10 (1.31), and -1.98 (15.1), respectively. Baseline CV was highest for KCMO (0.68) indicating greater variability around the mean and more sensitivity than HFC (0.48) and modified HFC (0.47) scores. Conclusion: The KCMO score measures GDMT intensity incorporating dosing and treatment eligibility, provides more granularity than existing methods, has clear interpretability, and can be adapted as performance measures evolve. Further study of its association with outcomes and usefulness for quality improvement are needed.
Abstract 12878: Inhibition of NK1.1 Signaling Attenuates Pressure Overload-Induced Cardiopulmonary Inflammation, Pulmonary IFN-γ Production, and Heart Failure Progression
Authors: Xiaochen He, Rui Xu, Lihong Pan, Umesh Bhattarai, Xiaoguang Liu, Heng Zeng, Jian-Xiong Chen, Michael E Hall, Yingjie Chen
Journal: Circulation (2023)

Introduction: Inflammation contributes to heart failure (HF) development, the progression from left ventricular failure to pulmonary remodeling, and the consequent right ventricular hypertrophy and failure. Hypothesis: NK1.1 plays a critical role in Natural killer (NK) and NK T (NKT) cells, but the role of NK1.1 in HF development and progression is unknown. Methods: We studied the effects of NK1.1 inhibition on transverse aortic constriction (TAC)-induced cardiopulmonary inflammation, HF development, and HF progression in immunocompetent male mice of C57BL/6J background. Results: We found that NK1.1 + cell-derived interferon gamma + (IFN-γ + ) was significantly increased in pulmonary tissues after HF. In addition, anti-NK1.1 antibodies simultaneously abolished both NK1.1 + cells, including the NK1.1 + NK and NK1.1 + NKT cells in peripheral blood, spleen, and lung tissues, but had no effect on cardiopulmonary structure and function under control conditions. However, inhibition of NK1.1 signaling by anti-NK1.1 antibodies significantly rescued mice from TAC-induced left ventricular inflammation, fibrosis, and failure. Inhibition of NK1.1 signaling also significantly attenuated TAC-induced pulmonary leukocyte infiltration, fibrosis, vessel remodeling, and consequent right ventricular hypertrophy. Moreover, inhibition of NK1.1 signaling significantly reduced TAC-induced pulmonary macrophage and dendritic cell infiltration and activation. Conclusions: Our data suggest that inhibition of NK1.1 signaling is effective in attenuating systolic overload-induced cardiac fibrosis, dysfunction, and consequent pulmonary remodeling in immunocompetent mice through modulating the cardiopulmonary inflammatory response.
Abstract 16636: Correlation Between Interatrial Block Detected by High-Resolution Electrocardiography and Echocardiographic Markers of Left Atrial Cardiomyopathy
Authors: Javier C Barcos, Juan D Humphreys, Iván A Tello Santacruz, Maria Luz Fernandez Recalde, Juan Pablo Guzman, César R Cáceres Monié
Journal: Circulation (2023)

Introduction: Left atrial cardiomyopathy (LACM) involves electromechanical changes in the left atrium (LA) and is linked to atrial fibrillation (AF) and embolic stroke. Several diagnostic ECG and transthoracic echocardiogram (TTE) parameters have been suggested, but information about their interrelationship is limited. Hypothesis: To evaluate if partial or advanced interatrial block (IAB) using high-resolution 12-lead ECG (HR-ECG) is related to TTE indicators of LACM. Methods: A retrospective analysis of consecutive patients aged over 18 was performed. The evaluation included HR-ECG (signal-averaging technique, ≥ 200 cycles, QRS-triggered, 0.25-262 Hz bandwidth, 1000 samples/sec) and TTE. Exclusion criteria: AF, pacemaker/ICD carriers, heart surgery history, poor ultrasound window, or significant ECG noise. Inferior leads (DII, DIII, aVF) classified patients into three groups: no IAB, partial IAB (P wave ≥ 120 ms), and advanced IAB (typical/atypical patterns with negative aVF terminal component). TTE parameters of LACM considered were LA volume indexed to body surface area (LAVI), PA-TDI (surface ECG onset P wave to A' peak of LA lateral wall on Tissue-Doppler Imaging), and PALS (peak atrial longitudinal strain) during reservoir phase. Results: Of 851 patients, 533 met the inclusion criteria. Both IAB groups had a higher prevalence of TTE indicators of LACM (Table 1), and a statistically significant correlation was found between P wave duration (PWD) and TTE markers of LACM (Figure 1). Conclusions: Patients with partial or advanced IAB (assessed by HR-ECG) show a higher prevalence of TTE markers of LACM and a significant correlation between PWD, LAVI, PA-TDI, and PALS.
Abstract 18152: Clinical Impact and Mechanism of De Novo Aortic Insufficiency During Percutaneous Ventricular Assist Device Support for Cardiogenic Shock
Authors: Keitaro Domae, Masatoshi Hata, Tomohiko Sakamoto, Noriko Kodani, Junki Yokota, Masaru Matsuda, Hiromi Tsuji, Asako Mike, Hiroyuki Hao, Kei Nakamoto, Yasuhiro Ichibori, Yoshiharu Higuchi, Takafumi Masai, Yoshiki Sawa
Journal: Circulation (2023)

Introduction: Recently, percutaneous ventricular assist device (p-LVAD) has been widely applicable for cardiogenic shock. Clinically significant aortic insufficiency (AI) is contraindication for p-LVAD, nevertheless p-LVAD itself can cause de novo AI (dAI) during the support. However the detail of dAI during p-LVAD support was not fully investigated. The aim of this study was to evaluate the clinical impact of AI during p-LVAD support and also investigate the mechanism and risk factor of dAI. Methods: Seventy-seven consecutive patients who underwent p-LVAD support (average age 66.7 years, Impella CP/2.5 in 65 and 5.5/5.0 in 12 cases) from 2018 to 2022 were retrospectively evaluated. The average support periods was 8.0±6.9 days. dAI was defined as development of AI ≥ moderate during p-LVAD support. Aortic valve pathology was examined using autopsy specimens in eight patients. Results: Three patients had AI ≥ moderate before p-LVAD support and underwent surgical intervention (AVR in 2 and AV repair in 1) during p-LVAD support. dAI was observed in 8 patients (10.3%, moderate in 7 and severe in 1). Moderate dAI in four of these patients improved after cardiac recovery and weaning of p-LVAD support. However, in 3 other patients with dAI ≥ moderate developed hemodynamic instability and deceased due to heart failure. In only a patient, moderate dAI remained after p-LVAD weaning with stable hemodynamics. Progression of AI after p-LVAD removal was not observed in all patients. In-hospital mortality was higher in the patient with dAI (75.0 vs. 47.8%, p=0.14). Pathological evaluation revealed hemorrhagic change at LV side of aortic valve with hemosiderin-laden macrophages in 3 autopsy specimens, which suggested contact of p-LVAD catheter. The univariate analysis identified mild AI before p-LVAD support as independent risk factor for dAI (Odd ratio 5.5, 95%CI 0.074-0.45, p&lt;0.001). Conclusions: Our study demonstrated that de novo AI frequently occurred during p-LVAD support and had a negative impact on hemodynamics and prognosis. Interference with aortic valve by the p-LVAD catheter may cause and exacerbate AI, even in the cases with pre-existing mild AI. Surgical intervention is essential to improve hemodynamics for severe and permanent AI during p-LVAD support.
Abstract 15257: The “Free Choice” Diet-Induced Obese Nonalcoholic Steatohepatitis Hamster, a Clinically Relevant Model for Evaluating Drugs Targeting Heart Failure With Preserved Ejection Fraction
Authors: Rana Assaly, Francois Briand, Emmanuel Brousseau, Julie Maupoint, Caroline Dubroca, Thierry SULPICE
Journal: Circulation (2023)

Intro: Heart failure with preserved ejection fraction (HFpEF) is frequently associated with multiple comorbidities including nonalcoholic steatohepatitis (NASH) and obesity. Drug development for HFpEF is partly hampered by the limitations of preclinical models, such as diet-induced obese mouse and rat. Hypothesis: To overcome these limitations, we recently established a nutritional hamster model developing obesity, with human features for dyslipidemia NASH, and HFpEF. To confirm the relevance of our model, we tested whether the clinical benchmarks empagliflozin (EMPA, a SGLT2 inhibitor), vardenafil (VAR, a PDE5 inhibitor) and semaglutide (SEMA, a GLP-1r agonist) would improve HFpEF. Methods: To induce obesity, NASH and HFpEF, hamsters were fed with a free choice diet, which presents hamsters with a choice between control chow or high fat/cholesterol diet, and normal or 10% fructose water for 20 weeks. Obese hamsters were then randomized based on echocardiography parameters, i.e., E/A ratio and ejection fraction (EF) and were treated QD for 5 weeks with vehicle, EMPA (30mg/kg), VAR (10mg/kg) or SEMA (0.06mg/kg). Chow fed hamsters were used as control. Results: Compared with control, echocardiography in obese hamsters showed cardiac remodeling, preserved systolic function and normal EF. Free choice fed hamsters had impaired diastolic function with higher E/A (2.0±0.1 vs 1.41±0.03 in control, p&lt;0.001), while the inverted E’/A’ (0.8± 0.1 vs 1.3±0.04, p&lt;0.001), a sign of relaxation default, suggested restrictive filling pattern. Increased E/E’ suggested higher filling pressure (18-20 vs 12-14 in control, p&lt;0.01). Plasma NT-proBNP levels were also increased (p&lt;0.05 vs. control). Compared with vehicle, all drug treatments alleviated diastolic dysfunction: E/A returned to control values (E/A=1.4-1.5) with VAR (p&lt;0.001 vs. vehicle), EMPA (p&lt;0.01) and SEMA (p&lt;0.05). As well, E’/A’ was normalized (p&lt;0.01 for all), and E/E’ was also reduced (p&lt;0.05 for all). EMPA and VAR reduced NT-proBNP levels (p&lt;0.05 vs. vehicle). Conclusion: Our data indicate that, VAR, EMPA and SEMA improved diastolic function in the obese NASH hamster. This novel model provides a unique alternative to mice and rats limitations for evaluating drugs targeting HFpEF.
Abstract 15073: Response to PCSK9 Inhibition in Homozygous Familial Hypercholesterolemia Patients is Variable in Different Regions of the World and According to Age
Authors: Frederick J Raal, Vimal Mehta, Meral Kayikcioglu, Dirk J Blom, Preeti Gupta, Ronen Durst, Emil A Asprusten, Traci Turner, El Mustapha Bahassi, Jeffrey Vest, Kate Caldwell, David Kallend, Evan A Stein
Journal: Circulation (2023)

Background: Reductions in LDL-C with PCSK9-inhibition in HoFH subjects are highly variable even within populations with the same pathogenic variants. Whilst initial studies were done in HoFH patients of European decent, recent studies from India and other countries with novel pathogenic variants as well as studies in paediatric patients have shown substantially less response to PCSK9 inhibition. In the global phase 3 LIBerate-HoFH trial, we evaluated two different PCSK9 inhibitors, lerodacibep (LIB) 300 mg SC QM and evolocumab (EVO) 420 mg SC QM in genetically confirmed HoFH patients on stable background lipid lowering therapy. Methods: Eligible patients (age ≥10 years) were randomized to either LIB or EVO for 24 weeks (Period A) followed by an 8 week ‘washout’ and crossed over to the alternate drug for the next 24 weeks (Period B). In a post-hoc analysis, the mean reduction in average LDL-C with both drugs were evaluated according to various world regions and age. Results: Of 65 who entered Period A, 56 completed both periods: 31 in USA/Europe/Israel/South Africa; 15 in India and 10 in Turkey. Mean baseline LDL-C was 401 mg/dL; 55% were female and 19(34%) were adolescents aged &lt;18 years. For the total population, the mean (SE) reduction in average LDL-C was -9.6% (3.25) on LIB and -11.7% (3.65) on EVO (p=0.44, NS). LDL-C reductions varied considerably in different regions and response was poorer in the adolescent subjects. However, reductions in LDL-C of ≥15% were seen in 26.8% (n=15) with LIB and 37.5% (n=21) with EVO - Table. Conclusions: Reductions in LDL-C achieved with PCSK9-inhibition in HoFH subjects are highly variable and differ according to region and age. However, given the clinically significant reductions in LDL-C in 1/3 of patients including patients from India and Turkey with null/null or novel variants, PCSK9 inhibition should remain part of standard of care for HoFH patients who remain with elevated LDL-C levels despite treatment with statin and ezetimibe.
Abstract 15886: High Visceral to Subcutaneous Fat Ratio is Correlated With Increased Cardiovascular Events in Elderly Patients With Suspected Coronary Artery Disease
Authors: Yushi Oyama, Kyuhachi Otagiri, Takuya Miyagi, Takahiro Sakai, Hiroshi Kitabayashi
Journal: Circulation (2023)

Introduction: Although abdominal fat distribution (AFD), presented as the ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) area (V/S ratio), is possibly associated with an increased risk of cardiovascular disease (CVD), the relationship between V/S ratio and its long-term outcomes have rarely been studied. Methods: We assessed 942 consecutive patients with suspected coronary artery disease who underwent computed tomography (CT) angiography. The patients also underwent plain abdominal CT to measure VAT and SAT areas. The V/S ratio was calculated to assess the AFD. The patients were classified into four groups based on the median V/S ratio and median age (i.e., 0.625 and 69 years, respectively). We examined the association between the V/S ratio and its long-term outcomes in each age group. The primary outcome was major adverse cardiac events (MACEs), including all-cause death, any coronary revascularization, acute coronary syndrome, and emergent hospitalization due to CVD. Results: Over a median follow-up of 1507 days, the incidence of any cardiovascular event was not associated with the V/S ratio among younger patients; however, among older patients, the incidence of MACEs, all-cause death, and any coronary revascularization was higher in the high V/S ratio group than in the low V/S ratio group. According to the Kaplan-Meier analysis, only older patients had a significantly lower MACE-free survival rate in the high V/S ratio group than in the low V/S ratio group, and no differences were noted among the younger patients in both groups. After adjusting for traditional coronary risk factors, high V/S ratio was independently associated with incidence of MACEs in older patients (Figure). Conclusion: A high V/S ratio was associated with an increased risk of MACEs in older patients only. Therefore, a high V/S ratio may be an important risk factor for CVD, particularly in older patients. However, AFD did not affect CVD prognosis among younger patients.
Abstract 12768: Recurrent Hyperkalemia is Associated With Higher Rates of Cardiovascular Outcomes and All-Cause Mortality in Patients With Chronic Kidney Disease: The Revolutionize III Study
Authors: George L Bakris, Abiy Agiro, Alexandra Greatsinger, Manasvi Sundar, Fan Mu, Erin Cook, Helen Guo, Elaine Louden, Ellen Colman, Pooja Desai
Journal: Circulation (2023)

Introduction: The impact of recurrent hyperkalemia (rHK) on the time to cardiovascular (CV) outcomes and mortality in patients with chronic kidney disease (CKD) has not been well studied. This real-world study described and compared rates of CV outcomes and all-cause mortality between patients with rHK and matched patients without HK (nonHK). Methods: Patients with rHK were matched 1:1 to nonHK controls via exact and propensity score matching with the date of rHK or nonHK as index. Patients were adults with stage 3 or 4 CKD identified from Optum’s de-identified Market Clarity Data spanning 1/2016 to 8/2022. For each outcome sample, the corresponding CV events in baseline were excluded. CV outcomes included major adverse cardiovascular events plus (MACE+; all-cause mortality or inpatient [IP] heart failure, myocardial infarction, or stroke) and IP cardiac arrhythmia. Rates of CV outcomes and mortality were compared between matched cohorts using cause-specific Cox proportional hazard models and reported as hazard ratios (HR) with 95% confidence intervals (CI). Subgroups analyses were conducted by renin-angiotensin-aldosterone system inhibitor (RAASi) use at index. Results: Of 6,337 matched pairs, mean age was 73.3 years and 47.7% of patients were female. Patients with rHK compared to nonHK had higher rates of CV outcomes, including MACE+ (N = 5,258, HR=1.53 95% CI=[1.43, 1.65]) and IP arrhythmia (N = 5,485, 1.94 [1.74, 2.16]) (all p&lt;0.001, Figure 1 ). Results were consistent in the RAASi subgroup (MACE+: 1.46 [1.31, 1.63]; IP arrhythmia: 1.84 [1.57, 2.16], both p&lt;0.001). Patients with rHK also had higher rates of mortality (Overall: N = 6,337; 1.29 [1.20, 1.38]; RAASi subgroup: 1.25 [1.11, 1.41], both p&lt;0.001) compared to nonHK controls. Conclusions: This study demonstrates that patients with CKD and rHK had significantly higher rates of mortality, MACE+, and IP cardiac arrhythmia compared to matched patients with CKD and nonHK.
Abstract 16387: Speckle-Tracking Echocardiographic Features of Cardiac Amyloidosis in Patients With HFrEF
Authors: Ibolya Csecs, Adarsh Katamreddy, Elie Flatow, Shaunak Mangeshkar, Nikita Singh, Natalia Nazarenko, Maria-Irene Barillas Lara, Aldo L Schenone, Leandro Slipczuk, Mario J Garcia
Journal: Circulation (2023)

Introduction: The role of speckle-tracking echocardiography (STE) for establishing the diagnosis of cardiac amyloidosis (CA) has been primarily studied in patients with preserved EF (HFpEF). Hypothesis: We sought to determine the prevalence of abnormal STE indices among HF patients with CA who have reduced EF (HFrEF). Methods: We reviewed electronic health records to identify patients consecutively referred for the evaluation of CA by Tc99m PYP imaging between December 2014 to December 2020. Only patients with LVEF &lt; 40% were included. Left ventricular (LV) and atrial (LA) global and segmental strain, relative apical sparing (RELAPS), and end-diastolic wall stress (EDWS) were measured using STE (TomTec). Results: Among 138 patients, 65 (47%) were identified with CA+; they were older compared to amyloid negative group (CA-). LV-GLS was similar in both groups. However, basal segments LV strain, LA strain, and LA fractional area change (LA-FAC) were significantly lower, and RELAPS was higher in CA+ patients (Figure). End-diastolic wall stress was also lower in CA+ (for all p&lt; 0.01, Figure). After adjusting for age and sex, impaired basal segment strain, EDWS, and LA-FAC remained independent predictors of identifying CA+ patients (p&lt; 0.05). Conclusions: The presence of CA among HFrEF patients is associated with regional variability in LV strain, greater impairment of LA function, and lower EDWS.
Abstract 15376: Candidacy and Fate of Right Heart Failure Patients Undergoing Tricuspid Valve Surgery
Authors: Karolis Bauza, Lucy Thuita, Eugene H Blackstone, Gosta B Pettersson, Haytham Elgharably
Journal: Circulation (2023)

Objective: There are no current guidelines for risks and benefits of cardiac surgery for patients with right heart failure (RHF). In this study, we analyzed pre-operative RHF variables aiming to assess candidacy for surgery and impact of tricuspid intervention. Methods: We retrospectively identified 522 patients with severe (+3 or more) tricuspid regurgitation (TR) who underwent cardiac surgery between 01/2007 and 01/2014 . The mean follow up was 4.7 years (± 4.3 years). Cluster analysis was performed using preoperative RHF clinical and hemodynamics variables, and outcomes after surgery were assessed. Results: Cluster analysis divided the cohort into three distinct clusters representing different phenotypes of patients with RHF-associated TR (cluster 1: 220 patient, cluster 2: 224 patients, cluster 3: 78 patients). Cluster I had highest concomitant left-sided valve procedure (72% mitral valve surgery, p&lt;.0001) with best RV function (fractional area change % 35 ± 13, p=.0002). Cluster II had highest MELD score (14 ± 4, p&lt;.0001), creatinine (1.4 ± 0.6, p&lt;.0001), and worst RV function (fractional area change % 30 ± 12, p=.0002). Cluster III had the most dilated right heart with right atrial area of 42 ± 14 mm, p&lt;.0001 and RV area in diastole 42 ± 10 mm, p&lt;.0001. Survival was best in Cluster I followed by Cluster III while worst in Cluster II (70%, 59%, and 29% at 8-years, respectively), Figure 1. Recurrent TR was highest in Cluster III, followed by Cluster II while least in Cluster I at 10-years (9%, 8%, and 5%, respectively). Conclusions: Cluster analysis of RHF identified three distinct groups of patients presenting for cardiac surgery. Pre-operative RV dysfunction was associated with worse clinical outcomes and need careful assessment before surgery. Pre-operative right heart dilation was associated with recurrent TR for which more aggressive tricuspid repair or even replacement might be considered.