tbuckley/cabot-search huggingface dataset:
Abstract 4143066: C-C Chemokine Receptor Type 2 and Matrix Metalloproteinases Molecular Interaction in Rat Abdominal Aortic Aneurysm
Authors: Mohamed Zaghloul, Santiago Elizondo Benedetto, Batool Arif, Gyu Seong Heo, Hannah Luehmann, Yongjian Liu, Robert Gropler, Mehran Sadeghi, Mohamed Zayed
Journal: Circulation (2024)

Background: Abdominal aortic aneurysm (AAA) in part results from complex molecular interactions between inflammatory cytokines. C-C chemokine Receptor Type 2 (CCR2) and Matrix Metalloproteinases (MMPs) have fundamental roles in the initiation, progression, and rupture of AAAs. We hypothesized that in a preclinical rodent AAA model CCR2 and MMP molecular interactions are essential for AAA progression and rupture. Aim: Our study aimed to assess the correlation and molecular interaction between CCR2 and MMP in AAAs following pharmacological targeting of each. Methods: Male Sprague-Dawley rats underwent intraluminal infrarenal perfusion of the aorta using porcine pancreatic elastase (PPE), daily β-aminopropionitrile (BAPN) to promote AAA rupture. Starting on postoperative day 3 (POD3), rats were treated with either a MMP inhibitor (MMPi; GM6001) via daily intraperitoneal injection or a CCR2 inhibitor (CCR2i; RS504393) via daily oral gavage. On POD6, the treated and control groups underwent in vivo aortic diameter measurement using ultrasound then their AAA tissues were harvested. The rate of rupture of AAA was observed until POD14 (Fig 1A). Results: CCR2 was directly correlated with total, pro and active MMP9 (r=094, r=0.88, r=0.88, P&lt;0.05 respectively; Fig 1B-D). CCR2i significantly decreased total, pro, and active MMP9; while MMPi significantly reduced CCR2 (Fig 1G-J). Both CCR2i and MMPi significantly decreased AAA diameter and rupture rate (Fig 1E-F). The CCR2i group had significantly lower IL-1β, IL-10, IL-18, and MCP-1 levels compared to the control group (Fig 1K-O). However, MMPi group had significantly lower IFN-γ and higher preserved elastin content compared to the control group (Fig 1Q-S). Both treatment groups had significantly lower IL-17A and higher TNF-α levels (Fig 1M-R). Conclusion: Our study demonstrates a positive correlation between CCR2 and MMP9, suggesting their interdependence in AAA pathogenesis. Furthermore, inhibition of either CCR2 or MMP9 reduced AAA development, highlighting their potential as therapeutic targets. Future studies using CCR2 and MMP9 knockout mice are needed to further elucidate the mechanistic interaction between these molecules in AAA pathogenesis.
Abstract 4143160: Serotonin Norepinephrine Reuptake Inhibitor is Associated with Lower Mortality Among Patients Presenting with Takotsubo Cardiomyopathy
Authors: Garba Rimamskep Shamaki, Anderson Anuforo, ISRAEL SAFIRIYU, David Corteville, Monika Sanghavi, Katherine Clark
Journal: Circulation (2024)

Background: Serotonin-norepinephrine reuptake inhibitors (SNRIs) inhibit the presynaptic reuptake of serotonin and norepinephrine and are widely used in the treatment of depression and neuropathic pain. Some studies suggest that the use of SNRIs may play a role in the etiology of takotsubo cardiomyopathy. Objectives: We aim to evaluate the impact of serotonin-norepinephrine reuptake inhibitors on the clinical outcomes of patients with takotsubo cardiomyopathy. Method: The authors retrospectively analyzed the deidentified patient data from TriNetX research network. Patients aged ≥18 years with a principal diagnosis of takotsubo cardiomyopathy were identified from January 1, 2003, to December 31, 2023. Patients with a history of myocarditis, pheochromocytoma, acute myocardial infarction, cocaine-related disorders, opioid-related disorders, and patients on with an active prescription for 5-fluorouracil, capecitabine, gemcitabine, and trastuzumab were excluded. Additionally, patients on selective serotonin reuptake inhibitors, tricyclic antidepressants, modafinil, armodafinil, methylphenidate, bupropion and atomoxetine were excluded. We used propensity score matching to adjust for potential confounders. The final study population was divided into two cohorts: Patients on SNRIs (duloxetine, venlafaxine, and desvenlafaxine) and patients not on SNRIs. The primary outcome was all-cause mortality, and the secondary outcome was takotsubo cardiomyopathy-related complications. Results: A total of 16,853 patients with a diagnosis of takotsubo cardiomyopathy were identified, of which 2,482 (14.7%) were on SNRIs at the time of diagnosis. The SNRIs cohort was slightly older (mean age 64.1 vs. 63.4 years). Patients on SNRI had a higher proportion of Whites (76.2% vs. 66.5%). After propensity score matching, patients on SNRI had lower 7-day mortality (OR, 0.59; 95% CI, 0.41 – 0.84, p&lt;0.01), cardiac arrest (OR, 0.58; 95% CI, 0.40 – 0.84, p&lt;0.01), ventricular fibrillation (OR, 0.496; 95% CI, 0.248 – 0.995, p=0.04), and atrial fibrillation and flutter (OR, 0.74; 95% CI, 0.57 – 0.97, p=0.03). At 1 year, patients on SNRI had lower mortality (OR, 0.80; 95% CI, 0.67 – 0.96, p=0.02). On subgroup analysis, the use of duloxetine or venlafaxine alone was independently associated with lower 7-day mortality. Conclusion: The use of SNRIs among patients presenting with takotsubo cardiomyopathy is associated with lower mortality and lower takotsubo cardiomyopathy-related complications.
Abstract 4143128: Understanding the Circumflex Aortic Arch Anatomy is Critical in Transcatheter Aortic Valve Replacement and Critical Bicuspid Aortic Valve Stenosis.
Authors: Merrina Lan, Konstantinos Boudoulas, Matthew Henn, William Marshall
Journal: Circulation (2024)

Case description: A 64-year-old male was referred for transcatheter aortic valve replacement (TAVR) due to critical bicuspid aortic valve stenosis (Figure 1A/B) with multiple episodes of unexplained syncope. A multidisciplinary discussion determined that he was at high surgical risk due to multiple comorbidities, including developmental delay, and prior renal transplantation with baseline serum creatinine of 1.8 mg/dL. Transfemoral and trans-subclavian arterial approaches for valvular replacement were not anatomically feasible due to the circumflex aortic arch (Figure 2A/B). Left transcarotid approach was considered due to the location of the vessel as the first branch of the ascending aorta (Figure 2B, 3A) but was unsuitable due to significant left carotid artery calcification. Thus, the decision was to perform a transaortic approach under general anesthesia. A right femoral artery sheath was inserted, and a wire was advanced to the aortic root (Figure 2B) for pigtail placement used to guide positioning during TAVR. A mini upper hemi-sternotomy was performed and J-ed into the right second intercostal space. The pericardium was suspended, and two concentric purse string sutures were placed in the aorta at the site of sheath placement. The valve was crossed and following valvuloplasty, the 29-mm Edwards SAPIEN 3 valve was delivered across the aortic valve annulus and deployed following balloon inflation with rapid ventricular pacing (Figure 3A). Postoperative echocardiography showed no prosthetic stenosis (Figure 3B) and no valvular or paravalvular regurgitation. Discussion: To our knowledge, this is the first report of a transaortic TAVR performed on a patient with a circumflex aortic arch. Circumflex aortic arch is a rare congenital anomaly and poses challenges to transcatheter aortic valve interventions from the extremities. This case illustrates the potential of transaortic TAVR as treatment for symptomatic aortic stenosis when there are no other options for access. Multidisciplinary collaboration and comprehensive imaging are critical in tailoring individualized cardiovascular intervention in patients with congenital anatomical variations.
Abstract 4143148: Feasibility of Volumetric Echo-PIV for Assessing Right Ventricular Blood Flow in Pulmonary Hypertension
Authors: Mohammad Hashemi, Nancy Salinas, Tawnya Brown, Antonina Caudill, Susan Jackman, Yuri Matusov, Siddharth Singh, Gianni Pedrizzetti, Arash Kheradvar
Journal: Circulation (2024)

Background: Pulmonary hypertension (PH) is a progressive condition leading to right ventricular (RV) dilatation and failure. It is hypothesized that RV remodeling can be predicted by changes in the complex three-dimensional (3D) RV blood flow. Early identification of these changes could help prevent establishing overt PH. This study tests the feasibility of volumetric Echo-PIV (V-Echo-PIV) technique that considers conservation of mass principle and RV wall dynamics to assess 3D RV blood flow field using standard clinical echocardiography equipment. Hypothesis: To assess whether V-Echo-PIV can differentiate between normal and pulmonary hypertension states without requiring high-fidelity replication of actual blood flows. Goals: Distinguishing RV blood flow in PH with or without RV dysfunction compared to the normal state. Methods: Followed by Optison™ injection, contrast echocardiography using a Philips EPIQ CV9 system and 3D matrix probe (x5-1) was performed to capture B-mode images of the RV. The V-Echo-PIV method estimated 3D RV blood flow velocities, refined by iterative correction to comply with RV geometry and mass conservation. Global flow properties such as kinetic energy and vortex impulse were calculated to distinguish between normal and pathological conditions. Results: The study compared healthy RV with the RVs from patients with pulmonary hypertension, with a normal-sized RV and with a dilated and dysfunctional RV. Evaluation of the iterative flow estimation process showed rapid convergence, confirming the robustness of the refinement approach. Blood flow visualization revealed distinct patterns during diastolic filling and systolic ejection (Fig. 1). Quantitative analysis showed reduced intensity of cycle-averaged kinetic energy, the energy dissipation, and enstrophy along with diastolic average of vortex impulse in patients compared to the control subject, indicating altered blood flow dynamics in PH (Figs. 2 and 3). Conclusions: Results show PH patients have altered flow properties even without overt RV dysfunction based on the qualitative visualization and the global metrics of blood flow. Further studies are needed to validate clinical value and ensure statistical significance. Nevertheless, this study demonstrates the potential of V-Echo-PIV, enhanced by the principles of mass conservation and RV geometry dynamics, to distinguish between normal and diseased conditions without necessitating high-fidelity replication of actual blood flows.
Abstract 4143156: Can Ventricular-Paced 12-Lead ECG Markers Predict Sudden Cardiac Death?
Authors: Thien Tan Tri Tai Truyen, Audrey Uy-Evanado, Kotoka Nakamura, Harpriya Chugh, Kyndaron Reinier, Sumeet Chugh
Journal: Circulation (2024)

Introduction: Specific markers on the sinus rhythm ECG are independently associated with increased risk of sudden cardiac death (SCD) with several published ECG risk scores. However due to distinctive activation of the heart, ventricular-paced (VP) ECGs are typically excluded from these studies, especially in the general population. Hypothesis: Markers on the VP ECG can predict risk of SCD in the general population. Methods: We conducted a case-control analysis in an ongoing community-based study of SCD in the Northwestern US (catchment population ~ 1 million; 2002-2020). SCD cases were included if they were aged ≥18 years, had archived ECGs performed prior to and unrelated to SCD that demonstrated continuous ventricular pacing. Control participants with identical ECG selection criteria and no history of ventricular arrhythmias or cardiac arrest were recruited from the same geographical area. Individuals with biventricular pacing and fusion rhythm were excluded. The ECG markers analyzed included QRS duration, QT, QTc, JTc, Tpeak-end, and heart rate. Results: Among 104 cases and 36 controls meeting criteria, VP SCD cases exhibited significantly longer QRS duration (median 172 ms, interquartile range [IQR] 157-192 vs. 161 ms, IQR 144-172, p=0.02), QTc (median 521 ms, IQR 495-560 vs. 511 ms, IQR 483-529 ms, p=0.001), and Tpeak-end interval (median 113 ms, IQR 97-124 vs. 99 ms, IQR 84-111, p=0.02) than VP controls. The highest quartile of QRS duration, QTc, and Tpeak-end were associated with 3.9, 7.6, and 5.2-fold higher odds of SCA, respectively, compared to the lowest quartiles. After performing multivariable regression analysis with demographic factors and comorbidities, QRS duration and Tpeak-end remained independent predictors of SCA (Figure). Conclusion: Our findings suggest that specific markers from ventricular paced ECGs are also associated with SCD. Further investigation is warranted to validate these results in other populations and to explore the implications for SCD risk stratification in the previously neglected sub-group of individuals with ventricular-paced rhythms.
Abstract 4143173: B Cell CXC Chemokine Receptor Type 5 Expression Predicts Left Ventricular Functional Improvement and Neurohormonal Improvement After Cardiac Resynchronization Therapy
Authors: Kenneth Bilchick, Jesse Cochran, Hema Kothari, Chantel McSkimming, Derek Bivona, Eli Zunder, Stefan Bekiranov, Coleen McNamara
Journal: Circulation (2024)

Introduction: B cells infiltrate the heart in a CXC chemokine receptor type 5 (CXCR5)-dependent manner and influence inflammation and remodeling. Yet whether CXCR5 expression on circulating B cells can be used as a marker to identify patients more likely to respond to pacing therapies for heart failure (HF) like cardiac resynchronization therapy (CRT) is unknown Research Question: Is the amount of CXCR5 expression on circulating B cells in humans prior to CRT associated with measures of left ventricular (LV) functional and neurohormonal response to CRT? Hypothesis: We hypothesized that lower B cell expression of CXCR5 pre-CRT is associated with greater improvements in LV function and neurohormonal activation (B-type natriuretic peptide [BNP]) after CRT. Methods: Protein expression in cryopreserved peripheral blood mononuclear cells (PBMCs) was measured with cytometry by time of flight (CyTOF). CXCR5 expression in B cell subsets was evaluated before and six months after CRT in 24 patients. Cardiac magnetic resonance (CMR) was performed prior to CRT, and the LV end-systolic volume index (LVESVI) before and after CRT was assessed by echocardiography. Response was defined as a 15% reduction in the LVESVI six months after CRT. Results: In 24 patients with HF undergoing CRT, the median age was 68 years (IQR 61 to 75 years), 38% were female, and 15 were responders (R). The median pre-CRT serum BNP concentration was 178 pg/mL (IQR 94-251 pg/mL) in R and 430 (IQR 272-757 pg/mL) in non-responders (NR) (p=0.07). The median pre-CRT LVESVI was 74 mL/m 2 (IQR 60 to 103 mL/m 2 ) in R and 90 mL/m 2 (IQR 83 to 110 mL/m 2 ) in NR (p=0.19). Pre-CRT CXCR5 expression in naive B cells (CD27- IgDhiCD196lo IgMlo) was lower in R v. NR (p=0.0016) (Figure 1). The area under the receiver operating characteristic curve (AUROC) for response was 0.80 (p=0.0026) with B cell CXCR5 as the only predictor and 0.89 (p=0.0015) with both B cell CXCR5 and the pre-CRT CMR LV ejection fraction (LVEF) as predictors (Figure 2). The odds ratio for response per unit increase of B cell CXCR5 was 0.18 (p=0.027) in the latter model. Pre-CRT B cell CXCR5 expression was also correlated with the change in BNP six months after CRT (r=0.45, p=0.027) (Figure 3). Conclusions: B cell CXCR5 may be an important predictor of CRT response based on LV function and neurohormones even after adjustment for known predictors. Further investigation of B-cell CXCR5 for prognosis in HF patients undergoing CRT is of great interest.
Abstract 4143164: Autoimmunity and Sex Inform Clinical Outcomes of Non-Aortic Arterial Dissections
Authors: Yurilu Gonzalez Moret, Audry Chacin Suarez, M. Carolina Musri, Mounica Yanamandala, Kevin Lo, Joseph Loscalzo, Marie Gerhard-Herman, Arvind Pandey
Journal: Circulation (2024)

Background: Non-aortic arterial dissections (NAAD) are increasingly diagnosed on imaging but natural history of disease in women and men is poorly understood, and long-term outcomes are still not well-defined. NAAD pathobiology is broadly subdivided as either rheumatologic or non-rheumatologic, but whether this binary classification is relevant for clinical outcomes is not clear. Methods: Utilizing the TriNetX Research Collaborative Network containing nearly 90 million deidentified electronic health records, patients aged 18 years or older diagnosed with NAAD between January 1, 2014 to May 8, 2024 were stratified into two cohorts based on presence or absence of a diagnosed rheumatologic condition. Patients were identified using ICD-9/10 codes to include any code for a large or medium vessel arterial dissection and/or rheumatologic condition; patients with aortic dissection codes were excluded. Following propensity score matching for covariates, groups were analyzed for all-cause mortality and major adverse cardiovascular events (MACE) (stroke, cardiac arrest, acute myocardial infarction, heart failure) after 1 year and 5 years using Kaplan-Meier survival analysis with log-rank testing and Cox proportional hazard model. Results: A total of 64,984 patients were identified to have an ICD-9/10 code for a NAAD; 60,196 had no associated rheumatologic condition and 4,698 had a co-morbid rheumatologic ICD-9/10 code. Prior to propensity matching, NAAD patients with rheumatologic conditions were more likely to be older (59.6 vs 54.5 years), female (63% vs. 47%), and have a greater prevalence of cardiovascular risk factors (p &lt; 0.001 for all). After propensity matching, NAAD patients with rheumatologic conditions had higher all-cause mortality at 1 year (hazard ratio [HR] with 95% confidence intervals: 1.34 [1.12-1.60]) and 5 years (HR: 1.21 [1.07-1.38]) compared to non-rheumatologic NAAD patients. Non-rheumatologic dissection patients exhibited sex-biased outcomes, with mortality (1-year HR: 1.26 [1.17-1.35], 5-year HR: 1.25 [1.18-1.33]), MACE (5-year HR: 1.08 [1.01-1.15]), and need for vascular procedures (2.5% versus 2.05%, p &lt; 0.001) more likely to occur in men than women; conversely, rheumatologic dissection patients did not show sex-based differences. Conclusions: The presence of co-morbid rheumatologic conditions is associated with greater mortality in patients with NAAD. Sex is an important modifier of clinical outcomes in non-rheumatologic dissection patients.
Abstract 4143083: Cardiomyopathy in Pregnancy Complicated by Loeys-Dietz Syndrome
Authors: Pristine Mei, Lidija McGrath
Journal: Circulation (2024)

Case Description: A 28-year-old G2P1 woman presented at 27 weeks gestation with progressive dyspnea and lower extremity edema. She was found to have atrial fibrillation and flutter with RVR. Initial TTE revealed severely dilated left ventricle (LV) with reduced systolic function (EF 20-25%) (Figure 1). She remained in flutter despite diuresis, rate control with metoprolol and digoxin, cardioversion, and ablation. Initiation of guideline-directed medical therapy was limited by hypotension and pregnancy. She underwent a cesarean section at 32 weeks given ongoing arrhythmia and heart failure symptoms. Skin fragility and poor uterine tone were noted intraoperatively. This, in addition to her exam findings of arachnodactyly and hypertelorism, prompted genetic testing, which was positive for SMAD3 mutation consistent with Loeys-Dietz syndrome (LDS) type 3. Following delivery, spironolactone and enalapril were added in keeping with breastfeeding compatibility. Her arrhythmia burden continued to lessen. Repeat TTE showed EF of 35-40% and normal LV size. MRA of head to pelvis was notable for mild dilation of intrarenal abdominal aorta (2.5 cm) with no other vascular abnormalities. Discussion: Loeys-Dietz syndrome is an inherited connective tissue disorder caused by mutations in TGFBR 1/2, TGFB 2/3, and SMAD 3. It is characterized by multisystem involvement with cardiovascular, craniofacial, skeletal, and cutaneous features. Cardiomyopathy and arrhythmia have been described in a small number of cases. This case represents a rare manifestation of LDS diagnosed during pregnancy where hemodynamic changes likely precipitated development of symptoms and intraoperative findings, which informed additional testing and led to the diagnosis. More commonly, LDS presents with widespread arterial and aortic aneurysms that carry a high risk of dissection. Aortic dissection represents a major cause of early mortality in LDS often requiring intervention at a younger age. Complete vascular imaging is recommended at initial diagnosis, with regular surveillance thereafter. Beta blockers and angiotensin receptor antagonists are used in slowing aortic dilatation; cardiomyopathy and arrhythmias should be treated according to established guidelines.
Abstract 4143130: Regression of Inflammation in Chronic Chagas Disease Using Specific Anti-Parasitic Therapy Is Associated With an Activated Immune Profile Before Therapy and Increased Levels of IL-17 After Therapy
Authors: Silvana Silva, Walderez Dutra, Marcio Barros, Maria Nunes, Antonio Ribeiro, Ester Cerdeira Sabino, Léa Oliveira-da Silva, Carolina Koh, Andrea Carvalho, Fernanda Araujo, Iago Pacheco, Geanne Muniz Meira, Gustavo Henrique Silva Ambrósio Vieira, Iago Ferreira, Jean Machado, Jeroen Nyssen, Sofia Zanetti, Tiago dos Santos
Journal: Circulation (2024)

Background: Chagas disease (CD), caused by Trypanosoma cruzi, leads to chronic Chagas cardiomyopathy, one of the deadliest and most debilitating cardiopathies. Benznidazole (BZN) is the medication of choice in Brazil, effective during the acute phase, but its efficacy during the chronic phase is unclear. Aims: To determine if BZN treatment reduces cardiac inflammation and fibrosis via magnetic resonance imaging (MRI) and its association with the circulating immune profile of CD patients. Methods: We collected cardiac images and plasma from a cohort of CD patients before and 6 months after BZN treatment. We performed: 1- MRI of left and right ventricle function and volumes, T1 (MAPA T1), T2 mapping (MAPA T2), and extracellular volume (ECV); 2- analysis of soluble factors including cytokines, chemokines, and growth factors using the Bio-48 Plex Human Cytokine Screening Panel kit. Changes in the variables MAPAT1, MAPAT2, and ECV were used to classify the improvement of CD patients undergoing BZN therapy. Patients with the greatest reductions in these variables post-therapy, compared to pre-therapy, were considered to have greater clinical improvement. Thus, patients were divided into two groups: greater clinical improvement (GCI; n=15) and smaller clinical improvement (SCI; n=15) (figure 1). Data were analyzed using GraphPad Prism 8 software with statistical significance set at p&lt;0.05. Results: Analysis of MAPA T1, MAPA T2, and ECV showed a reduction of fibrosis/inflammation in patients after treatment as compared to before. Our data demonstrated that GCI patients had an activated systemic immune profile before treatment, with higher levels of NGF (p=0.04), CXCL-8 (p=0.03), CCL-7 (p=0.04), IL-12 (p=0.04), IL-13 (p=0.03), and IL-15 (p=0.03) compared to SCI patients (figure 2A). Interestingly, GCI patients displayed higher post-treatment levels of IL-16 (p=0.02) and IL-17 (p=0.048) (figure 2B). Conclusion: These results suggest that BZN treatment may reduce fibrosis/inflammation in cardiac tissue of CD patients and that an activated immune profile before therapy may predict therapeutic response. Additionally, increased levels of IL-17 post-therapy in GCI patients support IL-17's previously reported protective role in Chagas disease.