tbuckley/cabot-search huggingface dataset:
Abstract 4125252: Pre-Hematopoietic Stem Cell Transplantation Echocardiographic Indices and Post-Transplant Cardiovascular Outcomes
Authors: Sujay Kalathoor, Alexi Vasbinder, Tonimarie Catalan, Kristen Machado, Anis Ismail, Christina Hutten, Ian Pizzo, Yiyuan Huang, Pennelope Blakely, Mousumi Banerjee, Monika Leja, Salim Hayek
Journal: Circulation (2024)

Introduction: Hematopoietic stem cell transplantation (HSCT) is associated with adverse cardiovascular (CV) events including the development of heart failure (HF) and arrythmias. While transthoracic echocardiogram (TTE) is routinely obtained prior to HSCT, its role in predicting the incidence of HSCT related CV events is poorly understood. Methods: We used data from the Cardiovascular Registry in Bone Marrow Transplantation (CARE-BMT) study, a multicenter observational study of adult patients (aged ≥18 years) who underwent autologous/allogeneic HSCT for malignant or nonmalignant bone marrow disorders at the University of Michigan Health System (UMHS) and Rush University Medical Center from 2008-2019. In this analysis, we included patients from UMHS with a baseline TTE. Data on pre-HSCT TTE parameters and post-HSCT CV outcomes were collected through manual chart review. Left ventricular (LV) function and dimensions were categorized into normal, mildly abnormal, and moderately/severely abnormal based on American Society of Echocardiography guidelines. The primary outcomes were new-onset HF and atrial fibrillation/flutter post-HSCT. Analyses were conducted using a Fine-Gray model adjusted for the pre-HSCT CARE-BMT CV risk score. Results: Of the 2071 patients (mean age at HSCT 55.5 + 12.9 years; 59.5% male) with a pre-HSCT TTE (median 25 days pre-HSCT), 116 (5.6%) and 128 (6.2%) patients experienced HF and atrial fibrillation/flutter, respectively, over a median period of 2.2 years. Greater abnormalities in left ventricular internal diameter at end-diastole (LVIDd) and end-systole (LVIDs) were linearly associated with a higher risk of HF (P-trend 0.018 and 0.004, respectively) (Table). Similarly, moderately/severely abnormal LVIDd was associated with a 2.41-fold (95% CI: 1.07, 5.43) increase in risk of atrial fibrillation/flutter (Table). Pre-HSCT ejection fraction (EF) was not associated with either endpoint. Conclusion: LV dilation, even when mild, was notably associated with increased risk of developing new HF or atrial arrythmias post-HSCT, regardless of EF. Whether evidence of LV dilation should prompt the initiation of guideline directed medical therapy to minimize the risk of incident HF warrants further study.
Abstract 4125938: Novel Surgical Model of Thoracic Aortic Aneurysm Mediated by Vasa Vasorum Inhibition
Authors: Bryant Fisher, Tara Richards, Jennifer Hill, Yoojin Lee, Thomas Gleason, Julie Phillippi
Journal: Circulation (2024)

Objective: The adventitial layer of the aorta contains the network of microvessels known as vasa vasorum. Previous work by our team revealed deficient vasa vasorum associated with medial hypoxia and upregulated adventitial thrombospondin-1 (TSP-1), an anti-angiogenic molecule, in human aortic aneurysm. We hypothesize that heightened TSP-1 in the ascending thoracic aorta induces aneurysmal degeneration through its anti-angiogenic effects on the vasa vasorum. We tested this hypothesis in a rabbit model via peri-adventitial delivery of ABT-510, a thrombospondin peptide mimetic. Methods: The ascending aorta was exposed in New Zealand White rabbits (n=16) and treated with ABT-510 proximally and a vehicle control distally. Echocardiography was undertaken immediately prior to the procedure and 14 days post-operatively. Adventitial vasa vasorum were quantified from H&amp;E-stained sections. Elastin and collagen organization were assessed with Verhoeff-Van Gieson (VVG) and pentachrome staining as well as multiphoton microscopy. Immunodetection of Hypoxyprobe™ and alpha smooth muscle actin (αSMA) were also undertaken to identify hypoxia and smooth muscle cell content, respectively. Results: Echocardiography revealed an increase in aortic diameter over 14 days with ABT-510 treatment compared with control (42.27% ± 5.54 vs 20.99% ± 4.10, p=0.004). Histological analysis showed decreased vasa vasorum count (44.7 ± 9.19 vs 85.8 ± 12.89, p=0.048) and decreased vasa vasorum indexed cumulative area (0.013 ± 0.0037 vs 0.021 ± 0.0050 µm 2 / µm 2 adventitial area, p=0.019). Immunodetection of Hypoxyprobe™ showed evidence of increased hypoxia. VVG, pentachrome, and immunodetection of αSMA showed decreased elastin content, increased deposition of ground substance, and areas of smooth muscle cell loss . Multiphoton microscopy demonstrated fragmented elastin fiber microarchitecture and decreased collagen content (Fig 1). Conclusions: Our study findings demonstrate a novel, clinically relevant model for thoracic aortic aneurysm through vasa vasorum inhibition that recapitulates features of cystic medial degeneration. This translational model could enable development of targeted, pro-regenerative therapies that restore perfusion to the aortic wall.
Abstract 4124281: Dexmedetomidine for junctional ectopic tachycardia in patients undergoing tetralogy of Fallot repair: a meta-analysis of randomized controlled trials
Authors: Lucas Barbosa, Ivo Queiroz, Maria Defante, Pedro Romeiro, Vanio Antunes, Elisio Bulhoes, Beatriz X. Mendes, Catarina Silva, Camila Guida, Edna Barbosa, Thais Iwashita Lages
Journal: Circulation (2024)

Background: Junctional ectopic tachycardia (JET) occurs in 2 to 22% of patients after cardiac surgery for congenital heart diseases, including tetralogy of Fallot (TOF) repair. Dexmedetomidine emerged as a potential drug to prevent JET in these patients. This systematic review and meta-analysis aimed to evaluate the efficacy of dexmedetomidine in JET in patients undergoing TOF repair. Methods: We systematically searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCTs) analyzing the use of dexmedetomidine in patients undergoing TOF repair. We pooled risk ratios (RR) for binary outcomes, and mean differences (MD) for continuous outcomes with 95% confidence intervals (CI) with a random-effects model. We performed a trial sequential analysis (TSA) to assess the random risk of incidence of JET. We used R version 4.3.2 and TSA version 0.5.9.10 for statistical analyses. Results: Our meta-analysis included 5 RCTs comprising 546 patients, of whom 268 (49%) were randomized to dexmedetomidine. Compared with control, dexmedetomidine significantly reduced the incidence of JET (RR 0.46; 95% CI: 0.30 to 0.71; p&lt;0.05; Figure A). However, there were no significant differences in mortality (RR 0.45; 95% CI: 0.12 to 1.71; p=0.24; Figure B) between groups. In addition, dexmedetomidine also reduced the length of intensive care unit (ICU) stay (MD -7.75 hours; 95% CI: -15.08 to -0.41; p&lt;0.05; Figure C). There were no significant differences in ionotropic score (MD -0.97 ug.min/Kg; 95 % CI: -1.98 to 0.18; p=0.10; Figure D), and ventilation time (MD -2.29 hours; 95% CI: -8.39 to 2.41; p=0.27; Figure E). For the primary endpoint, TSA suggested a low risk of type 1 error; therefore, this result may be conclusive. Conclusion: In patients undergoing TOF repair surgery, dexmedetomidine significantly reduced the incidence of JET and the length of ICU stay.
Abstract 4124690: Effect of Colchicine on the Perivascular Inflammation Index of Coronary Computerized Tomography Angiogram: COPIX trial
Authors: Camila Barbosa, Carlos Serrano, FABIO GRUNSPUN PITTA, Eduardo Lima, FABIANA HANNA RACHED, Eduardo Martins
Journal: Circulation (2024)

Inflammation is an important pillar of atherogenesis in coronary disease. Studies have documented the prognostic power of measuring the attenuation of coronary perivascular adipose tissue (PVAT) and its good correlation as an early inflammatory biomarker in the atherogenesis process. Colchicine, a medication with well-documented anti-inflammatory action and with an impact on reducing cardiovascular outcomes, may influence reducing FAI (Fat Attenuation index) assessed by coronary tomography angiography. This study aims to evaluate the effect of colchicine in reducing coronary inflammation after 12 months of using the medication. Methods: Single- center, randomized, prospective, open, ongoing study, carried out at the Heart Institute of the University of São Paulo (InCor HCFMUSP). Forty patients with documentation of FAI ≥ 70 HU in the right coronary artery (RCA) and/or left descending artery (LAD) were randomized to receive colchicine 0.5 mg/day for a period of 12 months. The primary outcome was the quantification of FAI in both therapeutic groups (colchicine and control) after a 12-month follow-up. As a secondary outcome, we evaluated the variation in total atheroma volume, calcium score, progression or regression of high plaque findings, variation low attenuation plaque volume and clinical outcomes. Results: Forty patients were included between May 2021 to April 2023, of which 22 were in the Colchicine group and 18 in the Control group. As a primary outcome, no FAI improvement in RCA and LAD was documented after a 12-month follow-up. In the Colchicine group, the mean FAI in initial LAD of −70.37 ± 7.1 HU improved to −72.90 ± 6.2 HU, but without statistical significance (p = 0.82) and Control group −69,13 ± 7,7 HU to −71,73 ± 6,3 HU (p= 0,64). FAI RCA from − 67.69 ± 5.4 HU to −71.23 ± 4.7 HU, without significance (p = 0.10) in Colchicine group and – 65,48 ± 5,5 HU to −69,08 ± 7,8 HU (p = 0,19) in control group. Conclusion: To date, a total of 40 patients have been randomized. In this interim analysis, with 50% of the sample already undergoing control coronary CT angiography, no association was observed with the use of colchicine and improvement in coronary inflammation after 12 months of using the medication.
Abstract 4124828: The Methylation Landscape Of Human Aortic And Mitral Valvular Interstitial Cells
Authors: Sarah Halawa, Najma Latif, Yuan-Tsan Tseng, Ahmed Moustafa, Yasmine Aguib, Magdi Yacoub
Journal: Circulation (2024)

Valvular interstitial cells (VICs), the valves’ predominant cell type, are crucial in ensuring proper valve function, structural integrity, tissue repair and valve homeostasis. DNA methylation regulates gene expression profiles and a matched aortic to mitral human VIC methylation analysis will further our understanding of aortic- and mitral-specific VIC biology and pathobiology. This is the first study analyzing methylation profiles of non-diseased, matched human aortic and mitral VICs. We analyzed the differential methylation fingerprint of 12 non-diseased aortic and mitral VICs (10 males:2 females; 42–64 years) extracted from de-endothelialized leaflets using reduced representation bisulfite sequencing (RRBS) on HiSeq2500. Analysis of methylation levels of 12,676 genome-wide promoters revealed 651 differentially methylated (DM) promoters. The top 3 DM promoters were linked to TBX4 (meth diff = -28.9%, P = 5.2E-135) essential for valve morphogenesis, to EXOC3L2 (meth diff = 25.7%, P = 1.3E-92) and NT5DC2 (meth diff = -20.3%, P = 7.1E-69) potentially implicated in ECM remodeling, the former via vesicle trafficking and the latter through nucleotide metabolism. Functional classification and network analysis showed that the genes associated with the DM promoters were enriched for WNT-, TGFβ-, FGF-, EGF- and PDGF- pathways involved in physiological processes such as valve development, repair and VIC regulation, as well as pathological processes such as calcification. Additional enrichment was detected for integrin- and cadherin- pathways involved in cell-cell-ECM interactions and endothelin- and VEGF pathways involved in hemodynamic regulation. This work provides the first insight into the differential methylation regulation patterns of human aortic and mitral VICs. Understanding how aortic and mitral VICs are differentially epigenetically regulated will extend our understanding of their role in aortic- and mitral-specific leaflet homeostasis, susceptibility to disease processes and will contribute to dynamic innovative experimental setup designs, animal-free human-based modeling frameworks, tissue engineering and drug identification approaches.
Abstract 4124430: Calcinosis Cutis and Heart Failure---A Rare Manifestation Which Should Never Be Ignored!
Authors: Sabeeh Islam, Rabia Islam, Hamza Islam, Hamza Yousaf, Arshan Khan, Muhammad Hanif, Taher Sbitli, Sumi Singh
Journal: Circulation (2024)

Introduction: Heart failure can be a manifestation of underlying immune mediated myopathies like dermatomyositis/polymyositis which can present in broad range of clinical manifestations and sometimes dermatologic lesions can be the only manifestation of these underlying pathologies without typically involving the muscle weakness. Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue. There are five subtypes of calcinosis cutis, dystrophic, metastatic, idiopathic, iatrogenic and calciphylaxis. Case summary: 70-year-old female was evaluated for bilateral lower extremity swelling. Past medical history was significant for Graves’ disease, atrial fibrillation, mechanical aortic valve on warfarin, hypertension, hyperlipidemia, ascending aortic aneurysm. Work up showed BNP of 4700 pg/ml with normal cardiac enzymes. Transthoracic echocardiogram revealed newly reduced ejection fraction of 25—30% with severely dilated left ventricle. Patient refused cardiac catheterization. Nuclear stress test showed no evidence of ischemia. Patient was started on guideline directed medical therapy and biventricular Implantable cardioverter defibrillator device was placed as per cardiology recommendation. Six months later patient developed multiple calcinosis cutis lesions on abdominal wall requiring surgical excisions. Endocrine work up including PTH, serum Ca level was normal, however creatin kinase level was high normal (150 U/L). Serum aldolase was ordered which was found to be elevated(25U/L). Muscle biopsy was performed as per recommendations of rheumatology which was diagnostic of dermatomyositis. Patient was started on high dose steroids and methotrexate and eventually IV immunoglobulins as per rheumatology recommendation. Follow up echocardiogram revealed improved ejection fraction to 40--45% with resolution of any further lesion of calcinosis cutis afterwards. Conclusion: Cardiac involvement such as congestive heart failure can be a part of presentation of underlying untreated myopathies. Calcinosis cutis can be the only clinical manifestation of dermatomyositis affecting heart. Etiology of calcinosis cutis in patients with heart failure should be worked up properly. Dystrophic calcinosis cutis is the subtype associated with underlying autoimmune connective tissue diseases.
Abstract 4124604: Finding the Right Course: Unknown Source of Hemorrhage Following Endocardial-Epicardial Ablation for Ventricular Tachycardia
Authors: Kasen Culler, Graham Peigh, Weili Zhang, Nicholas Xiao, Albert Nemcek, Laura Davidson, Alexandru Chicos
Journal: Circulation (2024)

Background: Epicardial radiofrequency ablation via percutaneous access is a common technique for ventricular tachycardia (VT) ablation. Rapid identification of and response to complications can reduce morbidity and mortality. Objective: We present a case of epicardial VT ablation complicated by a distal left internal mammary artery (LIMA) transection secondary to subxiphoid sheath insertion. Report: A 66-year-old man with hypertrophic cardiomyopathy was referred for endo-epicardial ablation of recurrent VT. Pericardial access was obtained using coronary vein exit and carbon dioxide insufflation technique. An 8.5F sheath was advanced over an indwelling pericardial wire, and ablation was performed. Following ablation, 400cc of blood was aspirated from the pericardial space after replacing the 8.5F sheath with a standard pericardial drain. Urgent angiography revealed intact coronary arteries, coronary sinus (CS) and LIMA. The 8.5F sheath was re-introduced and bleeding ceased. CT scan revealed no myocardial or great vessel damage. Mild pericardial drainage continued overnight. The next day, IR angiography demonstrated transection of the distal LIMA from the indwelling sheath. The patient underwent placement of a back-up pericardial drain, followed by coil embolization of the injured artery without complication (Fig). Conclusion: This case highlights the importance of maintaining a broad differential during apparent complications of epicardial access and the importance of staying close to midline for epicardial puncture given anatomic variability. The differential for acute blood loss and pericardial effusion following epicardial ablation includes 1) coronary artery damage, 2) CS damage, 3) extracardiac vascular injury, and 4) right ventricular injury. When extracardiac vascular injury is suspected, multidisciplinary collaboration is essential.
Abstract 4124289: Changes in high-sensitivity cardiac troponin I and associated cardiovascular risk: Analyses From the FOURIER Trial
Authors: Paul Haller, Nicholas Marston, Andrea Bellavia, Petr Jarolim, Anthony Keech, Robert Giugliano, Marc Sabatine, David Morrow
Journal: Circulation (2024)

Background: Circulating high-sensitivity cardiac troponin I (hs-cTnI) is associated with the risk of future cardiovascular (CV) events in stable patients (pts). Data are scarce regarding changes of hs-cTnI in a stable setting. Aims: To study baseline and changes of hs-cTnI in pts with atherosclerotic CV disease (ASCVD), and the association with risk of major CV events. Methods: We measured hs-cTnI (Abbott ARCHITECT) at baseline (BL) and 24 weeks (wks) in 20,718 pts enrolled in a nested biomarker study of the FOURIER trial, which tested the PCSK9i evolocumab vs. placebo in pts with ASCVD on statin and LDL &gt; 70 or non-HDL &gt; 100 mg/dL. The primary endpoint was an adjudicated composite of CV death, MI, stroke, hosp. for unstable angina, or coronary revascularization. The HR (95% CI) across percent-change of hs-cTnI was investigated in pts with quantifiable hs-cTnI at BL and 24 wks (lower limit of quantification (LLOQ) 3.6ng/L) using restricted-cubic splines and Cox-PH models, adjusted for sex, age, LDL at BL, prior MI, randomized treatment, eGFR, DM, HTN, prior HF, and BMI. A Generalized Additive Model was used to predict event rates as a function of hs-cTnI BL and absolute change, flexibly evaluated with a non-linear interaction. All models were based on 3-year follow-up using landmark analysis from 24 wks. Results: Median age was 63 yrs (25 th , 75 th percentiles: 56, 69), 75.5% were male, 86.1% had CAD, 13.7% PAD, and 19.0% a prior stroke. Of these pts, 11,021 (46.8%) had hs-cTnI &gt; LLOQ at BL and 24 wks. The median hs-cTnI at 24 wks was 6.6ng/L (5 th , 25 th , 75 th , 95 th percentiles are: 3.7, 4.7, 11.9, 51.1 ng/L). The absolute event rate of the primary endpoint across hs-cTnI BL and depending on absolute hs-cTnI change to 24 wks is shown in Fig. A . Higher Hs-cTnI BL was associated with higher event rates (p &lt; 0.001). Additionally, absolute reductions and increases of hs-cTnI from BL to 24 wks resulted in reduced and increased event rates, respectively, across hs-cTnI BL . Additionally, relative decrease and increase of hs-cTnI from BL to 24 wks were associated with reduced and increased relative risk, respectively (p for overall effect &lt; 0.001, Fig. B ). Conclusion: Changes in hs-cTnI are associated with the risk of future CV events. Serial measurements of hs-cTnI may aid in reclassification of CV risk and the identification of pts whose CV risk changes with time.
Abstract 4124531: Digital Health Intervention to Enhance Optimization of Heart Failure Care: From Reciprocal Innovation using Human-Centered Design to Pilot Study
Authors: Beatriz Polachini, Ana Luiza Ciminelli, Rafael Lino, Victoria Bramucci, EDMAR RIBEIRO, Lilian Rezende, Erin Spaulding, Alexander Sandhu, Zahra Azizi, Andrea Beaton, Chris Longenecker, Antonio Luiz Ribeiro, Luisa Brant
Journal: Circulation (2024)

Introduction: Guideline-directed medical therapy (GDMT) for Heart Failure with reduced ejection fraction (HFrEF) reduces adverse events by 70%, but is underutilized. The Human Centered Design (HCD) methodology can be useful to build a strategy to optimize GDMT centered on patients’ demands and perspectives. We aimed to reciprocally innovate a telephone-based digital health intervention (DHI) from a Brazilian trial to an app co-developed for a US trial and iterate it again to the Brazilian context using HCD. We will evaluate the app’s usability and utility to facilitate HF GDMT optimization, considering barriers of the Brazilian public health system users, such as low literacy and socioeconomic status. Methods: Mixed methods study. Steps were carried out according to HCD method: (1) empathizing and identifying challenges, (2) suggesting solutions, (3) prototype development, (4) ranking features for feasibility and utility (5) engineering work and (6) prototype testing. In stages 1-3, semi-structured interviews were held with 10 HF patients and 2 health professionals. Steps 4 and 5 were done by the research team. In stage 6, we conducted a pilot study with 10 HFrEF patients, with at least one GDMT drug with an optimization gap. The primary outcome was the app’s usability assessed by an engagement score, and the app’s utility at 4 weeks. Secondary outcomes included change in self-care score using the European Self-Care Behavior Scale. After step 6, new interviews were carried out to capture the user experience and identify new iterations. Interviews were recorded and transcribed for content analysis. Results: The average engagement score was 80% (SD 16) and the app’s utility score was 82% (SD 8). The average self-care score increased by 32% (SD 25) at the end of the pilot. The main challenges were lack of knowledge about HF and self-care. Technical difficulties and lack of trust in the app to handle health data were mentioned. In the pilot, patients reported the app was easy to use and contributed to self-care and understanding of HF. Among the DHI components, teleconsultation was best evaluated, followed by the educational videos. The greatest challenge was connecting the blood pressure cuff and scale via Bluetooth. Conclusion: The app was well accepted and considered useful by patients. User contributions were fundamental to create tools that facilitate engagement and utility. The final product will be evaluated in a randomized, multicenter, clinical trial.