Aortic Root Research Articles

Comparison of Hemodynamic Performance, Three-Dimensional Flow Fields, and Turbulence Levels for Three Different Heart Valves at Three Different Hemodynamic Conditions.

The hemodynamic performance of different prosthetic heart valves is difficult to compare among studies due to a variety of test conditions and experimental techniques. Existing studies are typically limited to one family of valves (biological or mechanical) and testing conditions of 5l/min and often lack sufficient spatial resolution. To address these limitations, a pulse duplicator with a multi-view imaging system (Tomo-PIV) was employed to investigate the three-dimensional flow field in the aortic root of three different valves: a tri-leaflet mechanical heart valve (TRIFLO, Novostia), a bi-leaflet mechanical heart valve (On-X, Artivion), and a biological heart valve (Perimount, Edwards Lifesciences). The valves were tested at low (3l/min), normal (5l/min), and elevated (7l/min) cardiac output under hypotensive (40/60mmHg), normotensive (80/120mmHg), and moderate hypertensive (105/170mmHg) pressure conditions, respectively. Compared to the Perimount, peak mean velocity was - 33%, - 24%, - 18% for the TRIFLO and - 32%, - 20%, - 11% for the On-X at low, moderate, and elevated , respectively. Corresponding peak values decreased by - 66%, - 57%, - 44% (TRIFLO) and - 60%, - 50%, - 36% (On-X). At low , was lower for Perimount (1.07cm2) than for TRIFLO (1.47cm2) and On-X (1.52cm2), while it increased for elevated to 2.75cm2 (TRIFLO) and 2.16cm2 (Perimount and On-X). For all valves, increasing led to increased flow velocities, higher and higher levels of turbulence, and the spatial influence of the valve on the flow field in the ascending aorta was extended. peaked closer to the STJ than for TRIFLO and Perimount.

Pathogenesis and Surgical Treatment of Congenitally Corrected Transposition of the Great Arteries (ccTGA): Part III.

Congenitally corrected transposition of the great arteries (ccTGA) is an infrequent and complex congenital malformation, which accounts for approximately 0.5% of all congenital heart defects. This defect is characterized by both atrioventricular and ventriculoarterial discordance, with the right atrium connected to the morphological left ventricle (LV), ejecting blood into the pulmonary artery, while the left atrium is connected to the morphological right ventricle (RV), ejecting blood into the aorta. Due to this double discordance, the blood flow is physiologically normal. Most patients have coexisting cardiac abnormalities that require further treatment. Untreated natural course is often associated with progressive failure of the systemic right ventricle (RV), tricuspid valve (TV) regurgitation, arrhythmia, and sudden cardiac death, which occurs in approximately 50% of patients below the age of 40. Some patients do not require surgical intervention, but most undergo physiological repair leaving the right ventricle in the systemic position, anatomical surgery which restores the left ventricle as the systemic ventricle, or univentricular palliation. Various types of anatomic repair have been proposed for the correction of double discordance. They combine an atrial switch (Senning or Mustard procedure) with either an arterial switch operation (ASO) as a double-switch operation or, in the cases of relevant left ventricular outflow tract obstruction (LVOTO) and ventricular septal defect (VSD), intra-ventricular rerouting by a Rastelli procedure. More recently implemented procedures, variations of aortic root translocations such as the Nikaidoh or the half-turned truncal switch/en bloc rotation, improve left ventricular outflow tract (LVOT) geometry and supposedly prevent the recurrence of LVOTO. Anatomic repair for congenitally corrected ccTGA has been shown to enable patients to survive into adulthood.

SIRT1 mediates the inflammatory response of macrophages and regulates the TIMP3/ADAM17 pathway in atherosclerosis

ObjectiveMacrophage polarization and the resulting phenotype have versatile roles in atherosclerosis. The study aims to decipher the role of SIRT1 in regulating macrophage phenotypes and atherosclerosis development. MethodsTwo mouse lines of SIRT1△Mac/ApoE−/− and SIRT1fl/fl/ApoE−/− were fed with high-fat diet to generate atherosclerotic lesion. Mouse peritoneal macrophages were isolated and transfected with SIRT1-overexpressing vector or vector-null. ResultsThe SIRT1△Mac/ApoE−/− mice exhibited greater atherosclerotic lesions, stronger immunofluorescence staining for M1-like macrophage marker, iNOS, and weaker immunofluorescence staining for M2-like macrophage marker, Arginase-1, than the SIRT1fl/fl/ApoE−/− littermates. The gene expressions of M1 markers (IL-1β, IL-6, and iNOS) were increased and those of M2 markers (IL-10 and Arg-1) decreased in both aortic roots and peritoneal macrophages from SIRT1△Mac/ApoE−/− mice, whereas SIRT1 overexpression rectified the changes in M1/M2 expression. A declined expression of TIMP3 with an increased expression of ADAM17 was noted in SIRT1△Mac/ApoE−/− macrophages, whereas SIRT1 overexpression rescued TIMP3 expression and inhibited ADAM17 expression. ConclusionOur data suggest that SIRT1 deficiency may promote macrophage M1 polarization and regulate the TIMP3/ADAM17 pathway thus favoring atherosclerosis development, indicating an anti-atherosclerotic role of macrophage SIRT1.

Aortic Root Dilation and Genotype Associations in Phelan-McDermid Syndrome.

Phelan-McDermid syndrome (PMS) is a rare genetic neurodevelopmental disorder that results from the loss of one functional copy of the SHANK3 gene. While many clinical features of PMS are well-understood, there is currently limited literature on cardiovascular abnormalities in PMS. This report aims to evaluate the prevalence of aortic root dilation (ARD) among individuals with PMS and to understand if underlying genetic variation relates to risk for ARD. We present findings from 59 participants collected from a multisite observational study evaluating the phenotype and natural history of PMS. Individual echocardiographic and genetic reports were analyzed for aortic root measurements and genetic variant data, respectively. Our a priori hypothesis was that participants with chromosome 22 deletions with hg19 start coordinates on or before 49,900,000 (larger deletions) would have more instances of ARD than participants with deletion start coordinates after 49,900,000 (smaller deletions). Eight participants (14%) had ARD, and its presence was statistically significantly associated with large deletions (p = 0.047). Relatedly, participants with ARD had significantly more genes deleted on chromosome 22 than participants without ARD (p = 0.013). These results could aid in the identification of individuals with PMS who are at higher risk for ARD.

Application of preset coronary artery orifice patch in Bentall surgery

BackgroundBentall surgery is the main method for treating aortic root lesions, but traditional Bentall method is very difficult for patients with mild aortic sinus dilation to directly anastomose the coronary artery orifice with graft.Case presentationA 41-year-old man was admitted to hospital after severe chest pain. Computed tomography angiography(CTA)revealed a type A aortic dissection. Echocardiography showed moderate aortic valve regurgitation and an aortic sinus diameter of 38 mm( mm). The patient underwent emergency Bentall surgery (using a preset coronary artery orifice patch), total arch replacement, and implantation of a graft into the descending aorta. Follow-up echocardiography showed the patient cardiac function was good, and there was no residual leakage at the coronary artery orifice.ConclusionsThis method is an alternative to traditional Bentall surgery and is suitable for all aortic root lesions, especially those with mild aortic sinus dilation or concomitant aortic dissection.

Management of aortic disease in children with FBN1-related Marfan syndrome.

Marfan syndrome (MFS) is a hereditary connective tissue disorder with an estimated prevalence of 1:5000-1:10 000 individuals. It is a pleiotropic disease characterized by specific ocular, cardiovascular, and skeletal features. The most common cardiovascular complication is aortic root dilatation which untreated can lead to life-threatening aortic root dissection, mainly occurring in adult patients. Prompt diagnosis, appropriate follow-up, and timely treatment can prevent aortic events. Currently there are no specific recommendations for treatment of children with MFS, and management is greatly based on adult guidelines. Furthermore, due to the scarcity of studies including children, there is a lack of uniform treatment across different centres. This consensus document aims at bridging these gaps of knowledge. This work is a joint collaboration between the paediatric subgroup of the European Network of Vascular Diseases (VASCERN, Heritable Thoracic Aortic Disease Working Group) and the Association for European Paediatric and Congenital Cardiology (AEPC). A group of experts from 12 different centres and 8 different countries participated in this effort. This document reviews four main subjects, namely, (i) imaging of the aorta at diagnosis and follow-up, (ii) recommendations on medical treatment, (iii) recommendations on surgical treatment, and (iv) recommendations on sport participation.

Aortic Homografts in Surgical Management of Prosthetic Valve Endocarditis: A Case Series from Greece.

BACKGROUND Infective endocarditis (IE) is a severe, life-threatening, and relatively common complication after valve replacement operations, with incidence rates varying between 1.8% and 5.8%, with an in-hospital mortality rate of up to 20%. Common microorganisms are (listed by decreasing incidence) Streptococci, Staphylococcus aureus, Enterococci, bacteria of the HACEK group, and fungi. Treatment of IE is complex, typically involving prolonged courses of antibiotics. However, in cases of aortic prosthetic valve endocarditis, root abscess formation with involvement of the aorto-mitral skeleton is not uncommon and complex surgical intervention is required. One of the notable advancements in surgical management is the use of homografts for aortic root endocarditis. CASE REPORT We report the first case series of 8 patients successfully operated on for prosthetic valve endocarditis with extensive aortic root abscess formation in Greece at Onassis Cardiac Surgery Center with the use of aortic homograft. All cases were redo surgeries and had good outcomes. Interestingly, one of the cases had extensive aortic root involvement with abscess formation extending to the aorto-mitral fibrous skeleton, requiring aortic root replacement with homograft, aorto-mitral skeleton reconstruction with bovine pericardium and mitral valve replacement with a mechanical prosthesis. Two other patients required concomitant coronary bypass grafting of the right coronary artery with reversed saphenous vein grafts. CONCLUSIONS Aortic root replacement with aortic homograft is the preferred choice for prosthetic valve endocarditis with aortic root abscess formation. Despite the technical complexity needed for implantation, this option offers a second chance for survival in patients with this challenging condition.

Assessment of the Aorto-Septal Angle Post-Thoracic Endovascular Aortic Repair through Segmentation and the Semi-Automatic Analysis of Cardiosynchronized Computed Tomography Angiography Images.

The aim of this study was to inviestigate cardiac and arterial remodelling before and after thoracic endovascular aortic repair (TEVAR) by measuring the Aorto-Septal Angle (AoSA) and the geometric characteristics of the aorta. Five patients were prospectively included. Pre- and post-operative cardio-CTA scans were used to create patient-specific 3D models to calculate the AoSA, defined by the intersection of the aortic and left ventricular axes. Additionally, geometric parameters and the inclination of the ascending aorta (AA) were measured. The results demonstrated a variation between pre- and post-operative AoSA in all patients, with an increase in the case of an aneurysmal disease from 112.36° ± 8.21° to 117.16° ± 9.65° (+4.1%, p = 0.041) and a decrease in the case of aortic dissection from 113.62° ± 0.96° to 107.83° ± 1.45° (-5.1%). Additionally, an increase in the length of both the outer and inner curvatures of the AA was observed from 102.21 ± 10.17 mm to 105.73 ± 11.2 mm (+ 3.33% p = 0.016) and from 55.55 ± 9.53 mm to 58.35 ± 9.96 mm (+4.8%, p = 0.04), respectively. This study introduced a new repeatable and reproducible method for assessing the AoSA using cardiac-CTA images. Thoracic stent deployment changes the AoSA, potentially impacting long-term left ventricle hemodynamics.

Aortic root replacement is superior to isolated aortic valve replacement for aortic regurgitation secondary to Behcet's disease.

Aortic root replacement is superior to isolated aortic valve replacement for aortic regurgitation secondary to Behcet's disease.

David Procedure for Aortic Root Aneurysm in a Post-Mitral Valve Repair patient with Marfan’s Syndrome – a Case Report.

Marfan’s syndrome is a multisystem connective tissue disorder caused by mutation of FBN1 gene, frequently affects the human cardiac valves. These patients commonly die due to cardiovascular diseases. David procedure has been recognized as a durable treatment option in younger adults for aortic root replacement in aortic aneurysm. But performing a David re-implantation for aortic root replacement in a post cardiac (mitral valve repair/MVR) surgery patient is not an easy task. We hereby present a case of successful David re-implantation of aortic root in a young post MVR patient. (Bangladesh Heart Journal 2024; 39(2): 168-171

Lysyl oxidase expression in smooth muscle cells determines the level of intima calcification in hypercholesterolemia-induced atherosclerosis

IntroductionCardiovascular calcification is an important public health issue with an unmeet therapeutic need. We had previously shown that lysyl oxidase (LOX) activity critically influences vascular wall smooth muscle cells (VSMCs) and valvular interstitial cells (VICs) calcification by affecting extracellular matrix remodeling. We have delved into the participation of LOX in atherosclerosis and vascular calcification, as well as in the mineralization of the aortic valve. MethodsImmunohistochemical and expression studies were carried out in human atherosclerotic lesions and experimental models, valves from patients with aortic stenosis, VICs, and in a genetically modified mouse model that overexpresses LOX in CMLV (TgLOXCMLV). Hyperlipemia and atherosclerosis was induced in mice through the administration of adeno-associated viruses encoding a PCSK9 mutated form (AAV-PCSK9D374Y) combined with an atherogenic diet. ResultsLOX expression is increased in the neointimal layer of atherosclerotic lesions from human coronary arteries and in VSMC-rich regions of atheromas developed both in the brachiocephalic artery of control (C57BL/6 J) animals transduced with PCSK9D374Y and in the aortic root of ApoE−/− mice. In TgLOXCMLV mice, PCSK9D374Y transduction did not significantly alter the enhanced aortic expression of genes involved in matrix remodeling, inflammation, oxidative stress and osteoblastic differentiation. Likewise, LOX transgenesis did not alter the size or lipid content of atherosclerotic lesions in the aortic arch, brachiocephalic artery and aortic root, but exacerbated calcification. Among lysyl oxidase isoenzymes, LOX is the most expressed member of this family in highly calcified human valves, colocalizing with RUNX2 in VICs. The lower calcium deposition and decreased RUNX2 levels triggered by the overexpression of the nuclear receptor NOR-1 in VICs was associated with a reduction in LOX. ConclusionsOur results show that LOX expression is increased in atherosclerotic lesions, and that overexpression of this enzyme in VSMC does not affect the size of the atheroma or its lipid content, but it does affect its degree of calcification. Further, these data suggest that the decrease in calcification driven by NOR-1 in VICs would involve a reduction in LOX. These evidences support the interest of LOX as a therapeutic target in cardiovascular calcification.

Surgery versus surveillance for ascending aortic aneurysms in elderly patients

BackgroundWhether elderly patients with aortic root or ascending aortic aneurysm (ATAA) would benefit from the new surgical size threshold of 5.0 cm is unknown. This study aimed to evaluate the natural history of ATAA in elderly patients and to compare long-term outcomes of those who underwent initial surveillance versus surgery. MethodsPatients age ≥75 years with an ATAA ≥40 mm were categorized into 2 groups: initial surgery and initial surveillance. The primary outcome was all-cause mortality; Kaplan-Meier curves were plotted for survival. A multivariable Cox proportional hazard regression model was used to identify independent predictors of long-term mortality. ResultsThe study series comprised 300 patients, including 58 who underwent initial surgery and 242 who received surveillance between July 2010 and September 2022. In the surveillance cohort, the mean aneurysm growth rate was 0.10 cm/year. Comparing surveillance to surgery, at 8 years there was no difference in survival (mean, 77.8 ± 3.4% vs 71.8 ± 9.6%; P = .65). For 116 patients with an initial aneurysm diameter ≥5.0 cm, there was no difference in survival between the 2 groups at 8 years (76.5 ± 7.0% vs 68.4 ± 11.3%; P = .20). Larger body surface area (hazard ratio [HR], 1.44; 95% confidence interval [CI], 1.09-1.90; P = .01) and history of smoking (HR, 2.25; 95% CI, 1.27-3.98; P = .01) were identified as predictors of long-term mortality. ConclusionsIn our series of elderly patients with ATAA, there was no difference in 8-year survival between initial surveillance and surgical management, with a high competing risk of nonaortic mortality. Surveillance may be a reasonable alternative to surgery for selected older adults with ATAA <5.5 cm.

A new method for scaling inlet flow waveform in hemodynamic analysis of aortic dissection.

Computational fluid dynamics (CFD) simulations have shown great potentials in cardiovascular disease diagnosis and postoperative assessment. Patient-specific and well-tuned boundary conditions are key to obtaining accurate and reliable hemodynamic results. However, CFD simulations are usually performed under non-patient-specific flow conditions due to the absence of in vivo flow and pressure measurements. This study proposes a new method to overcome this challenge by tuning inlet boundary conditions using data extracted from electrocardiogram (ECG). Five patient-specific geometric models of type B aortic dissection were reconstructed from computed tomography (CT) images. Other available data included stoke volume (SV), ECG, and 4D-flow magnetic resonance imaging (MRI). ECG waveforms were processed to extract patient-specific systole to diastole ratio (SDR). Inlet boundary conditions were defined based on a generic aortic flow waveform tuned using (1) SV only, and (2) with ECG and SV (ECG + SV). 4D-flow MRI derived inlet boundary conditions were also used in patient-specific simulations to provide the gold standard for comparison and validation. Simulations using inlet flow waveform tuned with ECG + SV not only successfully reproduced flow distributions in the descending aorta but also provided accurate prediction of time-averaged wall shear stress (TAWSS) in the primary entry tear (PET) and abdominal regions, as well as maximum pressure difference, ∆Pmax, from the aortic root to the distal false lumen. Compared with simulations with inlet waveform tuned with SV alone, using ECG + SV in the tuning method significantly reduced the error in false lumen ejection fraction at the PET (from 149.1% to 6.2%), reduced errors in TAWSS at the PET (from 54.1% to 5.7%) and in the abdominal region (from 61.3% to 11.1%), and improved ∆Pmax prediction (from 283.1% to 18.8%) However, neither of these inlet waveforms could be used for accurate prediction of TAWSS in the ascending aorta. This study demonstrates the importance of SDR in tailoring inlet flow waveforms for patient-specific hemodynamic simulations. A well-tuned flow waveform is essential for ensuring that the simulation results are patient-specific, thereby enhancing the confidence and fidelity of computational tools in future clinical applications.

A Novel Echocardiography Feature-Tracking Algorithm for Stabilized Frame-to-Frame Extraction of Aortic Root Diameters in the Parasternal Long Axis

A Novel Echocardiography Feature-Tracking Algorithm for Stabilized Frame-to-Frame Extraction of Aortic Root Diameters in the Parasternal Long Axis

Elective root replacement increases the risk of type B dissection in patients with Marfan syndrome

ObjectiveMarfan syndrome is a genetic disorder with increased risk of aortic dissection. Currently, type A aortic dissection risk is mitigated by aortic root replacement with Dacron. It is unclear if root replacement increases the risk of distal aortic disease given the noncompliant nature of Dacron. MethodsAll adult patients with a diagnosis of Marfan syndrome at a single academic center, excluding those with history of dissection or concomitant arch repair, were studied (n = 322). Student t test or Wilcoxon Mann–Whitney test was used for continuous variables; chi-square or Fisher exact test was used for categorical variables. Propensity matching used age, sex, hypertension, race, body mass index, family history of Marfan syndrome, and genetic mutational class. Differences in freedom from type B aortic dissection were determined using the log-rank test. ResultsA total of 124 patients underwent root replacement compared with 198 patients with no prior aortic surgery. Median follow-up time was 9.90 years. Male sex, weight, and hypertension prevalence were higher in the root replacement group (P < .05). Distribution of fibrillin-1 mutations was homogenous (P > .9). Type B aortic dissection frequency in the root replacement group was higher (21% [n = 20] vs 4.2% [n = 4], P < .001). Aortic-related mortality was higher in the root replacement group (11% [n = 14] vs 3.5% [n = 7], P < .01). Distal aortic intervention frequency was higher in the root replacement group (P = .009). ConclusionsPatients with Marfan syndrome who undergo elective aortic root replacement appear to have a higher incidence of subsequent type B aortic dissection, independent of other risk factors. Careful consideration must be made to the management of the distal aorta in patients with Marfan syndrome who undergo root replacement.

Aortitis Secondary to Prosthetic Valve Endocarditis: A Rare Complication Unveiled

Abstract Introduction Aortitis includes both infectious and non-infectious inflammation of the arterial wall. Infectious forms have a worse prognosis, necessitating immediate diagnosis and treatment. We report a case of a patient with prosthetic valve endocarditis complicated with infectious aortitis and multiple embolic lesions, ultimately leading to death. Case presentation An 81-year-old man with an aortic valve bioprosthesis (Intuity 27 mm) presented with fever, dysuria, and ankle swelling. Laboratory showed leukocytosis, anemia, elevated NT-proBNP, and C-reactive protein. Echocardiography revealed a hyperechogenic mass on the bioprosthesis, confirmed as prosthetic endocarditis by transesophageal echocardiography, which also showed an aortic bulb aneurysm and a 9 mm arterial wall thickening. Blood cultures were positive for Staphylococcus aureus, and intravenous antibiotics were started. Thoracic computed tomography confirmed aortic root dilation and mural thickening, indicating infectious aortitis with multiple embolic lesions in the spleen and kidneys. The patient then suffered an intestinal sub-occlusion. The Heart Team decided against cardiovascular surgery due to frailty and high surgical risk. Despite initial hemodynamic stability, his condition deteriorated, leading to death. Conclusion This case presents a challenging scenario of prosthetic valvular endocarditis complicated by infectious aortitis, aortic aneurysm, and multiple thromboembolic lesions in a high-risk patient, ultimately resulting in death.

The Ross Procedure in Active Infective Endocarditis: A Comparison With Conventional Prostheses

BackgroundThe Ross procedure can be an ideal option in infective endocarditis (IE) due to greater resistance to infection. However, limited literature has highlighted the comparison with conventional prostheses in this setting. MethodsBetween February 2013 and September 2022, 25 patients (median age, 50 years) underwent a Ross procedure for IE (Ross group). The results were compared with those after other aortic valve procedures (aortic valve replacement and aortic root replacement) for IE (n = 37, other group. ResultsThe patients in the Ross group included more intravenous drug users and had more prosthetic valve endocarditis and annular abscess formation compared with the other group. Although cardiopulmonary bypass time and aortic cross-clamp time were significantly longer (P < .001 and P = .003, respectively) and the blood requirements were significantly higher (P = .001) in the Ross group, most postoperative short-term outcomes were equivalent between the 2 groups. During follow-up, 1 patient (4%) required reoperation in the Ross group, whereas 6 patients (16%) required reoperation in the other group. Freedom from composite events was significantly better in the Ross group (P = .04). Multivariable analysis found the Ross procedure, compared with other procedures, was a significant independent protective factor for composite end points (P = .03). ConclusionsFor IE, despite surgical complexity, the Ross procedure yielded short-term outcomes similar to other procedures. In the midterm, the Ross procedure provides a lower reoperation rate, resulting in significantly fewer composite events. The Ross procedure appears to be a better option for patients with IE, but long-term follow-up is necessary.

Long-term Results of Valve-Sparing Aortic Root Replacement in Acute Type A Aortic Dissection

BackgroundValve preservation in acute type A aortic dissection (ATAAD) can be accomplished with root repair or replacement. Long-term valve durability with root repair has been established, but limited data exist regarding long-term durability of valve-sparing root replacement (VSRR). In this study, long-term results of VSRR were compared with root repair in ATAAD. MethodsFrom 2005 to 2023, 866 patients underwent ATAAD repair, of which 675 underwent root repair and 191 underwent root replacement (VSRR, n = 65; Bentall, n =126). VSRR patients were compared with 123 patients who underwent valve resuspension and root repair with postoperative echocardiograms ≥1 year. ResultsVSRR patients were younger (VSRR, 44 ± 11 years vs root repair, 55 ± 13 years; P < .001). Preoperatively, 57% of VSRR and 35% of root repair patients had moderate or more aortic insufficiency. Cardiopulmonary bypass and myocardial ischemia times were significantly longer in VSRR (P < .001). Postoperative echocardiograms with ≥1 year follow-up were analyzed in 58 VSRR patients with median follow-up of 4.8 years (interquartile range, 3-12 years) and in 123 root repair patients with median follow-up of 3.6 years (interquartile range, 3-8 years). At 10 years, VSRR patients had superior freedom from more than mild aortic insufficiency (VSRR, 91% vs root repair, 49%; P < .001). At 10 years, freedom from aortic valve replacement was equivalent (VSRR, 98% vs root repair, 92%; P = .269). ConclusionsVSRR provides equivalent long-term valve durability as root repair in ATAAD, even in patients with moderate or severe aortic insufficiency. In select young patients who require root replacement during ATAAD repair, VSRR represents an ideal therapy.

Inhibition of CTLA-4 accelerates atherosclerosis in hyperlipidemic mice by modulating the Th1/Th2 balance via the NF-κB signaling pathway

ObjectiveThough an increased risk of atherosclerosis is associated with anti-CTLA-4 antibody therapy, the underlying mechanisms remain unclear. MethodsC57BL/6 mice were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibody twice a week for 4 weeks, after being injected with AAV8-PCSK9 and fed a Paigen diet (PD). The proportion of aortic plaque and lipid accumulation were assessed using Oil Red O staining, while the morphology of atherosclerotic lesions was analyzed with hematoxylin and eosin staining. Collagen content was evaluated through Picrosirius Red (PSR) staining, while inflammatory cell infiltration was examined with immunofluorescence staining. CD4+ T cells secreting IFN-γ and IL-4, which represent Th1 and Th2 cells respectively, were detected by flow cytometry and real-time PCR. Protein levels of p-IκBα, IκBα, p-p65, and p65 were determined by Western blot. ResultsInhibiting CTLA-4 exacerbated PD-induced plaque progression and promoted CD4+ T cell infiltration in the aortic root. The anti-CTLA-4 antibody promoted CD4+ T cell differentiation toward the Th1 type, as indicated by an increase in the Th1/Th2 ratio. Compared to the anti-IgG group, treatment with anti-CTLA-4 antibody significantly elevated the protein levels of p-IκBα and p-p65, as well as the mRNA levels of TNF-α, IL-6, ICAM-1, and VCAM-1. Inhibiting the NF-κB signaling pathway attenuated the overall pathological phenotype induced by the anti-CTLA-4 antibody treatment. ConclusionAnti-CTLA-4 treatment promotes the progression of atherosclerosis by activating NF-κB signaling and modulating the Th1/Th2 balance. Our results provide a rationale for preventing and/or treating atherosclerosis accelerated by anti-CTLA-4 antibody therapy in cancer patients.

Enhancing Guidewire Efficacy for Trans-radial Access: The EAGER Randomized Controlled Trial.

Background: The 1.5mm 'Baby J' hydrophilic narrow J tipped wire is a development of the standard 0.035" 3mm J tipped peripheral guidewire, designed to improve efficiency of transradial coronary procedures by safely navigating small caliber radial arteries to the aorta. There is currently a lack of evidence comparing the procedural success and safety of different peripheral guidewires used in transradial cardiac procedures. We compared the efficacy and safety of a narrow J tipped hydrophilic 0.035" wire (intervention - Radifocus™ 'Baby J' guidewire, TERUMO Co., Tokyo, Japan). versus standard fixed core (FC) 0.035" J wire (control). Methods: Investigator initiated, blinded, Australian, multicenter randomized trial in patients undergoing clinically indicated coronary angiography and/or PCI. Randomized 1:1 via sealed envelope method to use either the control or the intervention guidewire. The primary endpoint (technical success) was defined as gaining aortic root access with the randomized guidewire. Results: 330 patients were randomized between October 2022 - June 2023 (median age 69 years, 36% female, BMI 29 kg/m²). The primary endpoint was achieved more frequently in the intervention group [96% v 84%; mean difference 12% (95% CI 5.7-18.3); p<0.001]. Women assigned to the control wire experienced a higher failure rate compared to men (31% v 8% in men; p<0.001). Fluoroscopy time was significantly shorter in the baby J group (median 344 versus 491 seconds; p=0.024). The main mechanisms of failure using the control wire were radial artery spasm (15/26; 57%) and subclavian tortuosity (5/26; 19.2%). There were no differences in overall procedure times, MACE, or vascular complications between guidewires. Conclusions: A narrow 1.5mm J tipped hydrophilic guidewire resulted in greater technical success and reduced fluoroscopy time compared to the standard 3mm J tip non-hydrophilic guidewire. The guidewire is safe and demonstrated key incremental benefits for the trans-radial approach particularly in women.