tbuckley/cabot-search huggingface dataset:
Abstract 13298: Impact of Finerenone on Cardiac Biomarkers in Patients With T2D and Chronic Kidney Disease
Authors: Mario Berger, Andrea Scalise, Frank M Kramer, Karen Paraschin, Laura Goea, Peter Kolkhof, Katja Rohwedder, Adam Skubala, Sebastian Voss, Faiez ZANNAD, Peter Rossing
Journal: Circulation (2023)

Introduction: Finerenone is a non-steroidal, selective antagonist of the mineralocorticoid receptor (MR), which blocks MR-mediated sodium reabsorption and MR overactivation. In this biomarker substudy to FIDELITY, a pooled, pre-specified analysis of FIGARO-DKD and FIDELIO-DKD, NT-proBNP and cardiac troponin T (cTnT) levels were assessed to explore the effect of finerenone on cardiac markers. FIGARO-DKD and FIDELIO-DKD were two phase III trials investigating efficacy and safety of finerenone vs. placebo (PLC) on cardiorenal outcomes, in patients with T2D and CKD. Hypothesis: Finerenone impacts the levels of major cardiac biomarkers. Methods: Samples were collected prospectively from non-selected patients who consented to the biomarker study. At baseline (BL), this study included 1037 subjects with cTnT data and 1592 subjects with NT-proBNP data from 13 and 24 countries, respectively. Samples were analyzed at BL, 4, 12, 24, 36 and 48 months follow-up on treatment with finerenone or PLC. Treatment effects on biomarkers were computed by a linear mixed model, adjusted for age, gender, screening eGFR and UACR, history of CVD, BL biomarker levels and geographical region. Results: Both, NT-proBNP and cTnT increased over time in both arms, yet, the increase was significantly lower in the active arm compared to PLC, even though finerenone temporarily reduces eGFR. The maximum ratio (finerenone to PLC) was 0.82 (95% CI: 0.76 to 0.90) at month 4 for NT-proBNP, and 0.94 (95% CI: 0.892 to 0.995) for cTnT at month 36. Median levels of biomarkers at BL were 177 pg/mL (NT-proBNP, IQR: 74-426) or 18 pg/mL (cTnI, IQR: 7-27). Conclusions: In patients with T2D and CKD, finerenone, on top of maximum tolerated labelled RAS inhibition and standard of care co-medication, reduced plasma NT-proBNP and cTnT, biomarkers usually associated with cardiac stress and injury, and indicative of poor prognosis. Our findings are in line with outcome data from FIDELITY showing a 22% risk reduction for HF hospitalization1 and other findings suggestive of reduced adverse cardiac remodeling. This data provides supportive mechanistic insights for benefits on cardiorenal outcomes in FIDELITY, confirming preclinical findings as well as clinical data on short-term treatment effects on NT-proBNP.
Abstract 17436: A Diagnostic Copycat: Culture Negative Endocarditis of A Bioprosthetic Valve Presenting as ANCA Vasculitis
Authors: David E Hamilton, Katherine Fell, Kent Brummel, Kim Eagle
Journal: Circulation (2023)

A 59-year-old female with a history of bicuspid aortic valve (AV) complicated by aortic stenosis and ascending aortic aneurysm s/p bioprosthetic AV and ascending aorta replacement presented with a 6-month history of weight loss, fatigue, and lower extremity rash. Initial laboratory workup identified anemia, leukopenia, and acute kidney injury with proteinuria and microscopic hematuria. Further workup included negative blood cultures, elevated inflammatory markers, elevated rheumatoid factor, hypocomplimentemia, and ANCA positivity (PR3 Ab positive). Biopsy of her palpable purpuric rash demonstrated vascular immune deposition pattern consistent with leukocytoclastic vasculitis. Renal biopsy revealed focal and crescentic glomerulonephritis with immune complex deposition. CT abdomen noted mesenteric lymphadenopathy with fluid surrounding the thoracic aortic graft. Surface echocardiogram showed bioprosthetic AV replacement with diffuse cusp thickening without stenosis or regurgitation. At this point, a multidisciplinary team offered a broad differential diagnosis of inflammatory vasculitis versus culture-negative endocarditis with plan for further testing. Follow-up whole-body and cardiac PET scan identified FDG-avid abnormalities involving the aortic graft and AV with hypermetabolic soft tissue thickening surrounding the aortic root. Transesophageal echocardiogram confirmed AV thickening with a 1 cm mobile echodensity. Additional serologic testing identified positive Bartonella henselae IgG (1:8192) and IgM (&gt;1:20) titers. The final diagnosis was B. henselae prosthetic AV endocarditis and ascending aortic graft infection. She underwent repeat AV and ascending aortic graft replacement, with graft material positive for B. henselae PCR and was treated with a course of doxycycline and rifampin. B. henselae is a fastidious gram-negative bacterium that can cause culture negative endocarditis but is very rarely associated with aortic graft infection. This case highlights (1) a rare example of B. henselae aortic graft infection, (2) the difficulty in differentiating B. henselae endocarditis from inflammatory vasculitis, and (3) the importance of engaging multidisciplinary teams to solve difficult diagnostic cases.
Abstract 12591: 12,13-dihome and Noradrenaline Are Associated With the Occurrence of Acute Myocardial Infarction in Patients With Type 2 Diabetes Mellitus
Authors: Ning Cao
Journal: Circulation (2023)

Introduction: Acute myocardial infarction (AMI) is the most prevalent cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). However, strict blood glucose control does not always prevent the development and progression of AMI. Aims: Therefore, the present study aimed to explore potential new biomarkers associated with the occurrence of AMI in T2DM patients. Methods: A total of 82 participants were recruited, including the control group (n=28), T2DM without AMI group (T2DM, n=30) and T2DM with initial AMI group (T2DM+AMI, n=24). The untargeted metabolomics using LC-MS analysis was performed to evaluate the changes in serum metabolites. Then, candidate metabolites were determined using ELISA method in the validation study (n=126/T2DM group, n=122/T2DM+AMI group). Results: The results showed that 146 differential serum metabolites were identified among the control, T2DM and T2DM+AMI, Moreover, 16 differentially-expressed metabolites were significantly altered in T2DM+AMI compared to T2DM. Furthermore, three candidate differential metabolites, 12,13-diHOME, noradrenaline (NE) and estrone sulfate (ES), were selected for validation study. Serum levels of 12,13-diHOME and NE in T2DM+AMI were significantly higher than those in T2DM. Multivariate logistic analyses showed that 12,13-diHOME (OR, 1.491; 95% CI, 1.230-1.807, P &lt;0.001) and NE (OR, 8.636; 95% CI, 2.303-32.392, P =0.001) were independent risk factors for AMI occurrence in T2T2DM patients. The area under receiver operating characteristic (ROC) curve (AUC) were 0.757 (95% CI:0.697-0.817, P &lt;0.001) and 0.711(95% CI:0.648-0.775, P &lt;0.001), respectively. The combination of both significantly improved the AUC to 0.816 (95% CI:0.763-0.869, P &lt;0.001). Conclusions: 12,13-diHOME and NE may lead to understanding the possible metabolic alterations associated with AMI onset in T2DM population and serve as promising risk factors and therapeutic targets.
Abstract 15754: The Incidence and Effect of Cardiac Function Decline After Lower Extremity Revascularization
Authors: Yasser Jamil, Joshua Huttler, Dana Alameddine, Haoran Zhuo, Carlos Mena-Hurtado, Eric J Velazquez, Raul J Guzman, Cassius I Ochoa
Journal: Circulation (2023)

Introduction: The impact of cardiac function decline on major adverse limb events (MALE) following lower extremity revascularization (LER) in patients with peripheral arterial disease (PAD) has not been described. Methods: The electronic records of patients undergoing LER for PAD in a single center were reviewed. Two transthoracic echocardiograms were captured, the first within 6 months of LER and the second on later follow-up. Patients were then divided into 2 groups: cardiac function decline (decrease in left ventricular ejection fraction (EF) by ≥10%) or stable cardiac function (reduction in EF&lt;10% or improved EF). Patient characteristics and outcomes were compared, including MALE. Results: Of the 922 patients who underwent LER, 221 (24.0%) experienced a cardiac function decline. Out of the 701 patients with stable cardiac function, 599 (65.0%) had a &lt;10% reduction in EF, and 102 (11.0%) had an EF improvement. Patients with cardiac function decline were more likely to have diabetes mellitus and heart failure. Furthermore, patients with cardiac function decline were more likely to undergo open surgical revascularization. Patients with cardiac function decline demonstrated higher rates of periprocedural bleeding after initial LER. After a 3-year follow-up, patients with cardiac function decline had higher mortality and lower overall frequency of reinterventions. However, Kaplan-Meier analysis revealed no difference in freedom from MALE between the 2 groups. Conclusion: Patients with cardiac function decline after LER for PAD have increased mortality but no significant difference in limb outcomes compared to patients with stable cardiac function.
Abstract 12850: Ascorbic Acid Promotes Ventricular Myosin Light Chain-2 Protein Expression and Maturation of Human Induced Pluripotent Stem Cells Derived Cardiomyocytes
Authors: Yu Gao, liping Su, Yuhua Wei, Zhenyu Hu, Zhonghao Tao, Jean-Paul Kovalik, Tuck Wah Soong, Jianyi J Zhang, Jun Pu, Lei Ye
Journal: Circulation (2023)

Introduction: The potentially unlimited number of cardiomyocyte (CMs) derived from human induced pluripotent stem cells (hiPSCs) facilitates high throughput applications like cell transplantation, disease modelling, and cardiotoxicity testing during drug development. Despite promising progress in these areas, a major disadvantage that limits the use of hiPSC derived CMs (hiPSC-CMs) is their immaturity. Hypothesis: Ascorbic acid (AA) can promote ventricular myosin light chain-2 (MLC-2v) expression and maturation of hiPSC-CMs. Methods: Three hiPSC lines (PCBC-hiPSC, DP3-hiPSCs, and MLC2v-mEGFP-hiPSC) were differentiated into CMs (PCBC-CMs, DP3-CMs,a nd MLC2v-CMs, respectively) with or without retinoic acid (RA). hiPSC-CMs were either maintained up to day 30 of contraction (D30C), or D60C, or purified using lactate acid and used for experiments. Purified hiPSC-CMs were cultured in basal maturation medium (BMM) or BMM supplemented with AA for 14 days. The AA treated and non-treated hiPSC-CMs were characterized for sarcomeric proteins (MLC2v, TNNI3, and MYH7), ion channel proteins (Kir2.1, Nav1.5, Cav1.2, SERCA2a, and RyR), mitochondrial membrane potential, metabolomics, and action potential. Bobcat339, a selective and potent inhibitor of DNA demethylation, was used to determine whether AA promoted hiPSC-CM maturation through modulating DNA demethylation. Results: AA significantly increased MLC2v expression in PCBC-CMs, DP3-CMs, MLC2v-CMs, and RA induced atrial-like PCBC-CMs. AA treatment significantly increased mitochondrial mass, membrane potential, and amino acid and fatty acid metabolism in PCBC-CMs. Patch clamp studies showed that AA treatment induced PCBC-CMs and DP3-CMs adaptation to a ventricular-like phenotype. Bobcat339 inhibited MLC2v protein expression in AA treated PCBC-CMs and DP3-CMs. DNA demethylation inhibition was also associated with reduced TET1 and TET2 protein expressions and reduced accumulation of the oxidative product, 5 hmC, in both PCBC-CMs and DP3-CMs, in the presence of AA. Conclusions: Ascorbic acid promoted MLC2v protein expression and maturation of hiPSC-CMs. The effect of AA on hiPSC-CM was attenuated with inhibition of TET1/TET2 mediated DNA demethylation.
Abstract 14735: Fabry's Disease as a Potential Overlapping Diagnosis in Progressive Hypertrophic Cardiomyopathy
Authors: Mustafa Suppah, Hemalatha Narayanasamy, James Nelson, Said Alsidawi
Journal: Circulation (2023)

Background: Fabry's disease (FD), an X-linked lysosomal storage disorder, can present with cardiac manifestations similar to HCM. We aim to emphasize considering FD as a differential diagnosis in patients with HCM while highlighting the role of genetic testing in evaluating left ventricular hypertrophy (LVH). Cases Presentation: We present a case series of 3 patients with LVH. Despite initial clinical suspicion of primary HCM, genetic testing confirmed the diagnosis of FD. Patient 1: A 38-year-old male with no prior medical history presented with presyncope, lightheadedness, and chest tightness. EKG, Echo, and cardiac MRI suggested apical HCM. Genetic testing indicated FD. Patient 2: A 62-year-old male sought a second opinion regarding his diffuse HCM. EKG suggested RBBB. Echo showed a binary appearance of the myocardium, concentric LVH. Genetic testing confirmed FD. Patient 3: A 64-year-old male with a history of hypertension and renal disease underwent evaluation for kidney transplantation. Echo showed severely increased concentric LVH and Valsalva-induced intracavitary gradient/obstruction. Alpha-galactosidase level returned very low, suggesting FD, which was confirmed by genetic testing. Discussion: FD can be challenging to diagnose due to overlapping clinical and imaging features with HCM, leading to misdiagnosis and delayed management. Therefore, Genetic testing should be offered to all patients with suspected HCM to exclude phenocopies. Particularly, those with progressive HCM and atypical clinical features (renal disease and family history predominantly in males) and imaging features (conduction abnormalities on EKG, binary appearance on Echo). Early identification of FD enables appropriate management, including enzyme replacement therapy, potentially improving clinical outcomes. Conclusions: FD should be considered as a differential diagnosis in patients with HCM. Genetic testing plays a vital role in evaluating patients with HCM.
Abstract 15925: Comparative Mortality, Safety, and Cost Among Stroke Patients Who Received Implantable Loop Records Compared to Continuous External Cardiac Monitors
Authors: Sanket Dhruva, Omid Ameli, Rita F Redberg, Jaime Murillo, Christine E Chaisson, Ken Cohen
Journal: Circulation (2023)

Background: Implantable loop recorders (ILR) are increasingly used to screen for atrial fibrillation (AF) among patients with stroke, but real-world outcomes are lacking. Goal: To determine comparative effectiveness, safety, and costs of ILR compared with continuous external monitors (CEM) and Holter monitors in a real-world setting of patients with stroke. Methods: This retrospective cohort analysis used the Optum Labs Data Warehouse, which contains longitudinal, de-identified administrative claims. The cohort included patients with recent stroke who received cardiac monitoring from 1/1/2016 - 6/30/2021, comparing those with ILR to those with CEM (&gt;48 hours to 30 days) or Holter (≤48 hours). Eligibility criteria included: ischemic stroke during 6 month baseline; continuous enrollment with medical and pharmacy coverage; no evidence of pacemaker, implantable cardioverter-defibrillator, AF, left atrial appendage ablation, or oral anticoagulants. The primary outcome was 12-month all-cause mortality, secondary outcomes included new diagnosis of AF + initiation of anticoagulants, hemorrhagic stroke, and total and device-related costs. Final analyses were adjusted for CHA 2 DS 2 -VASc score. Results: Among 48,801 individuals, 18.9% received ILR, 59.5% CEM, and 21.6% Holter. Groups had similar demographics and comorbidities (Table). Compared to those with CEM, the ILR group had higher odds of a new diagnosis of AF plus initiation of anticoagulants (OR 2.27; (95% CI 2.09, 2.48)), and hemorrhagic stroke (OR of 1.60 (95% CI 1.34, 1.93)). There was no difference in mortality. Unadjusted direct medical cost of monitoring was substantially higher in the ILR group ($13,975) compared to CEM ($449) and Holter ($149). Conclusions: Although the use of ILRs was associated with increased detection and treatment for AF, there was no impact on all-cause mortality. ILR was associated with increased hemorrhagic stroke and higher costs.
Abstract 14635: Prognostic Value of Heart Rate Variability in Black Americans: The Jackson Heart Study
Authors: Muhammad Shariq Usman, Ali Salman, Stephen J Greene, Monique A Starks, Muhammad Umer Sohail, Camille Frazier-Mills, Hau-Tieng Wu, Wilfried Dinh, Robert J Mentz, Javed Butler, Marat Fudim, Mohammad Khan
Journal: Circulation (2023)

Background: The prognostic value of heart rate variability (HRV) in Black Americans (BAs), who have distinct cardiac risk profiles, is not well studied. We aimed to investigate the association between HRV, all-cause mortality, and cardiovascular events in the Jackson Heart Study (JHS). Methods: We analyzed data from JHS participants who had HRV readings at baseline (2000-2004). HRV was measured as the standard deviation between subsequent R-waves on a 12-lead EKG. Data were analyzed up to December 31, 2014. Outcomes of interest were all-cause mortality and cardiovascular events (composite of incident stroke and coronary heart disease). Cox regression models were used to estimate hazard ratios (HRs) for the hazard of events in participants with an HRV below the median versus those with an HRV above the median. Restricted cubic splines (RCS) were used to explore non-linear interactions. All analyses were adjusted for age, sex, smoking, clinically relevant comorbidities, and risk factors. Results: Among the 3627 participants (mean age: 55.1 years; female: 62.4%), the median [IQR] HRV was 22.3ms [13.7, 36.1]. At baseline, participants with HRV below the median had a higher prevalence of several cardiometabolic diseases. Adjusted Cox regression showed that HRV below the median was associated with a 32% increased hazard of all-cause mortality (HR: 1.32 [1.09, 1.60]; P = 0.005) and a non-significant increase in incident cardiovascular events (HR: 1.28 [0.99, 1.66]; P = 0.059); Figure 1A . RCS suggested HRV has a non-linear relationship with all-cause mortality (P-nonlinearity: 0.0076) and cardiovascular events (P-nonlinearity: 0.0162), with the hazard of events beginning to increase sharply at HRV &amp;lt;25ms ( Figure 1B ). Conclusion: BAs had a higher mortality hazard associated with lower HRV readings, specifically &amp;lt;25ms. Consumer wearable sensors commonly record HRV, and our findings suggest that HRV could serve as a practical prognostic tool for this population.
Abstract 16397: Inflammatory Biomarkers as Predictors of Systemic vs. Isolated Pocket Infection in Patients Undergoing Transvenous Lead Extraction
Authors: Anne Sophie Lacharite Roberge, Sandeep Toomu, Omar Aldaas, Gordon Ho, Travis L Pollema, Ulrika Birgersdotter-Green
Journal: Circulation (2023)

Intro: Cardiovascular implantable electronic device (CIED) infections are a common indication for device extraction. Early diagnosis and complete device and lead removal are crucial to reduce morbidity and mortality. The lack of clear infectious symptoms and signs make the diagnosis of CIED infections challenging and may delay referral for extraction. Methods: We performed a retrospective analysis of patients undergoing transvenous lead extraction for CIED infection at UCSD from 2012 to 2022 (n= 164). Our control group underwent extraction for non-infectious etiologies such as device malfunction, lead fracture or system upgrade (n=281). Patients were classified as systemic infection (n=88) or isolated pocket infection (n=68) based on the presence or absence of sepsis. Prospectively collected pre-operative procalcitonin (PCT), C-reactive protein (CRP), and white blood cell count (WBC) were compared between groups using Kruskal-Wallis and Dunn-Bonferroni tests. Results: PCT and WBC medians differed significantly between the systemic infection, the pocket infection, and the control groups (p&lt;0.001 and p=0.021 respectively). Pairwise comparisons revealed the systemic infection group had a higher PCT than the control group (p&lt;0.001), as well as the pocket infection group (p=0.009). There was no significant difference in PCT between the control group and the isolated pocket infection group (p=0.685). Regarding pairwise differences in WBCs, a higher value was only associated with systemic infection when compared with our control group (p=0.018). CRP levels were not significantly different between groups (p=0.117) and the difference was again limited to systemic infection vs control groups (p=0.017). Conclusion: In patients with CIED infections requiring extraction, systemic infection was associated with elevated pre-operative PCT when compared to isolated pocket infection and controls. Elevated WBCs and CRP levels were also associated with systemic infection. However, inflammatory biomarkers including PCT were not elevated in isolated pocket infections. The results suggest that inflammatory markers are not predictive to help with the diagnosis of pocket infections, which ultimately requires a high level of clinical suspicion.
Abstract 17043: Role of Child Opportunity Index on Neonatal Mortality and 1-Year Mortality in Infant Congenital Heart Disease: A Contemporary Population-Based Report
Authors: Paola Cota Phelan, Martina Steurer, John M Costello, Stephanie Santana, james Collins, Tonia Branche, Meesha Sharma, Laura Jelliffe-Pawlowski, Shabnam Peyvandi
Journal: Circulation (2023)

Introduction: Although mortality has declined among infants with congenital heart disease (CHD), racial/ethnic and sociodemographic disparities persist. The child opportunity index (COI) is a census-based metric of neighborhood conditions based on education, health/environment, and social/economic domains. We sought to determine the impact of COI on neonatal and 1-year mortality of infants with CHD. Hypothesis: We hypothesized that neighborhood sociodemographic factors as measured by COI would have a greater impact on longer-term outcomes. Methods: This is a retrospective population-based cohort in California (2011-2017) of infants with CHD who underwent a cardiac intervention in the first year of life. COI was categorized into high, moderate, and low. Each COI domain was evaluated. The primary outcomes included 1-year mortality, neonatal mortality prior to 30 days of life, and days alive out of hospital in the first year of life (DAOOH). Uni- and multivariable logistic and linear regression were used. Results: The sample included 9,729 infants with an overall 1-year mortality rate of 8.2% and neonatal mortality rate of 3.5%. After adjusting for race/ethnicity, maternal age, sex, CHD severity (RACHS-1 category), birth weight z-score, and gestational age at birth, the odds of 1-year mortality were significantly higher among infants from low compared to high COI (1.37, 95%CI: 1.13, 1.67). In contrast, the adjusted odds of neonatal mortality were not different in low compared to high COI (1.20, 95%CI:0.89,1.61). Low and moderate COI groups had significantly lower DAOOH compared to high COI (low: -10.30, 95%CI: -15.2, -5.4; moderate: -7.43, 95%CI: -12.96, -1.89). Results were similar for each COI domain ( Figure 1). Conclusion: Neighborhood factors reflecting the home environment influence outcomes beyond the neonatal period. Future studies are needed to determine whether targeting domains of the COI will mitigate ongoing risks of poor CHD outcomes.