Sex-related differences in outcome of thoracic aortic surgery.

BACKGROUND: Sex-related dissimilarities' influence on outcomes following thoracic aortic surgery is poorly understood. Our aim is to examine sex-related disparities in patients undergoing thoracic aortic aneurysm (TAA). METHODS: A total of 455 cases undergoing thoracic aortic aneurysm (TAA) surgery were consecutively enrolled between December 2009 and December 2015 in a Chinese hospital. Primary outcomes, including overall mortality and related risk factors, were evaluated. Cox regression is utilized to recognize the independent risk factor of these consequences. RESULTS: Females, compared to males, had greater indexed aortic diameters and higher aortic transvalvular pressure differences. For the location of aortic aneurysms, females had a higher rate of aortic arch involvement, while males had a higher rate of root involvement. Females underwent less frequent complex proximal aortic operations compared with males (29.5% versus 46.9%; p < 0.001). Women and men both had a lower rate of aortic transvalvular pressure difference and LV volume index 7 days after thoracic aortic surgery. The overall mortality for the women's groups (11%) was suggestively greater compared to 4.9% for the men's groups (p = 0.026). Renal failure and aortic arch involvement were the main risk factors associated with males' survival, while maximum indexed aortic diameter and cross-clamp time were the risk factors associated with females' survival. CONCLUSIONS: The outcome after TAA surgery was less favorable in women with significantly increased overall mortality. It highlights the need to focus on implementing personalized surgery strategies and gender-specific guidelines in treating female patients following TAA surgery.

Bicuspid Aortic Valve Disease With Early Onset Complications: Characteristics And Aortic Outcomes.

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults but can also cause childhood-onset complications. In multicenter study, we found that adults who experience significant complications of BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early onset BAV complications.

Long-term outcomes of chimney endovascular aneurysm repair procedure for complex abdominal aortic pathologies.

OBJECTIVES: To update our earlier experience and to evaluate long-term outcomes of chimney endovascular aortic repair performed for selected cases with complex abdominal aortic aneurysm. METHODS: A single-centre retrospective cohort study was conducted on 51 consecutive patients who underwent chimney endovascular aortic repair procedure, deemed unfit for open surgical repair and fenestrated endovascular aneurysm repair, from October 2009 to November 2019. Kaplan-Meier analyses were used to assess the estimated overall survival, freedom from aneurysm related mortality, freedom from reintervention, freedom from target vessel instability and freedom from type Ia endoleaks. RESULTS: Fifty-one patients (mean age, 77.1 ± 7.5 years) with a mean preoperative maximum aneurysm diameter of 74.2 (± 20.1) mm were included. Mean follow-up duration was 48.6 months (range. 0 - 136 months). Estimated overall survival at 5 and 7 years was 36.3% (± 7.1%) and 18.3% (± 6.0%), respectively. Freedom from aneurysm-related mortality was 88.6% (± 4.9%) at 7 years. Estimated freedom from type Ia endoleak at 7 years was 91.9% (± 3.9%). A total of 21 late reinterventions were performed in 17 (33%) patients. Most of them were performed to treat type II endoleaks with sac growth (47.6%, n = 10) and type Ib endoleak (23.8%, n = 5). Estimated freedom from reintervention at 7 years was 56.3% (± 7.9%). Estimated freedom from target vessel instability at 7 years was 91.5% (± 4.1%). CONCLUSIONS: The 7-year results of chimney endovascular aortic repair procedures performed in our centre confirm the long-term safety and effectiveness of this technique in a series of high-risk patients with large aneurysms. The present study has, to the best of our knowledge, the longest follow-up for patients treated with chimney endovascular aortic repair, and it provides data to the scarce literature on the long-term outcomes of this procedure, showing acceptable to good long-term results.

5-year Outcomes of Fenestrated and Branched Endovascular Repair of Complex Aortic Aneurysms Based on Aneurysm Extent.

OBJECTIVES: To evaluate the 5-year outcomes of fenestrated/branched endovascular aortic repair (F/BEVAR) for the treatment of complex aortic aneurysms stratified by the aneurysm extent. METHODS: Patients with the diagnosis of complex aortic aneurysm, who underwent F/BEVAR at a single center were included in this study and retrospectively analyzed. The cohort was divided according to the aneurysm extent, comparing group 1 (types I-III thoracoabdominal aneurysms-TAAA), group 2 (type IV TAAA), and group 3 (juxtarenal, pararenal, or paravisceral aortic aneurysms - JRAA, PRAA, PVAA). The primary endpoints were 30-day and 5-year survival. The secondary endpoints were technical success, occurrence of spinal cord ischemia, primary patency of the visceral arteries, freedom from target vessel instability, and secondary interventions. RESULTS: Of 436 patients who underwent F/BEVAR between July 2012 and May 2023, 131 presented with types I-III TAAA, 69 with type IV TAAA, and 236 with JRAA, PRAA, or PVAA. All cases were treated under a physician-sponsored IDE protocol with a patient-specific company-manufactured or off-the-shelf device. Group 1 had significantly younger patients than group 2 or 3 respectively (69.6 ± 8.7 vs 72.4 ± 7.1 vs 73.2 ± 7.3, P < .001) and had a higher percentage of females (50.4% vs 21.7% vs 17.8%, P < .001). Prior history of aortic dissection was significantly more common among patients in group 1 (26% vs 1.4% vs 0.9%, P < .001), and mean aneurysm diameter was larger in group 1 (64.5 vs 60.7 vs 63.2 mm, P = .033). Comorbidities were similar between groups, except for coronary artery disease (P < .001) and tobacco use (P = .003), which were less prevalent in group 1. Technical success was similar in the three groups (98.5% vs 98.6% vs 98.7%, P > .99). The 30-day mortality was 4.5%, 1.4%, and 0.4%, in groups 1, 2, and 3, respectively, and was significantly higher in group 1 when compared to group 3 (P = .01). The incidence of spinal cord ischemia was significantly higher in group 1 compared to group 3 (5.3 vs 4.3% vs .4%, P = .004). The 5-year survival was significantly higher in group 3 when compared to group 1 (P = .01). Freedom from secondary intervention was significantly higher in group 3 when compared to group 1 (P = .003). At 5 years, there was no significant difference in freedom from target vessel instability between groups or primary patency in the 1652 target vessels examined. CONCLUSIONS: Larger aneurysm extent was associated with lower 5-year survival, higher 30-day mortality, incidence of secondary interventions, and spinal cord ischemia. The prevalence of secondary interventions in all groups make meticulous follow-up paramount in complex aortic aneurysm patients treated with F/BEVAR.

The "Bundle Wire" Technique: A Novel Approach to Cannulating Challenging Target Vessels Using Multiple Fine Atraumatic Guidewires That Together Serve as a Stiff Guidewire.

PURPOSE: To present a novel technique that enables safe and effective cannulation of target vessels with challenging anatomy during fenestrated/branched endovascular aortic repair (F/B-EVAR). TECHNIQUE: Following deployment of the F/B-EVAR endograft, the target vessels (TVs) are cannulated. The bundle wire technique provides a solution to challenging TVs and uses multiple fine atraumatic guidewires that together serve as a stiff guidewire. The technique can be executed in 2 ways using: (1) one 0.018 inch and one 0.014 inch guidewire or (2) three 0.014 inch guidewires. We demonstrate the technique in a case of a complex abdominal aortic aneurysm treated using branched EVAR in which the left renal artery with severe ostial stenosis was catheterized using the bundle wire technique. CONCLUSIONS: The bundle wire technique offers a technically feasible and economically viable solution for facilitating catheter and bridging stent delivery in anatomically challenging TVs during F/B-EVAR. It is a useful addition to the therapeutic armamentarium available to physicians for accessing demanding TVs.

A novel TGFßR2 splice variant in patient with aortic aneurysm and family history for aortic dissection: a case report.

We report the clinical presentation and genetic screening of a 31-year-old man with dilatation of the aortic root and ascending aorta and a positive family history for aortic dissection and sudden death. A novel heterozygous variant in a splice acceptor site (c.1600-1G>T) of TGFßR2 gene was identified by using a targeted multi-gene panel analysis. Bioinformatics tools predicted that the c.1600-1G>T variant is pathogenic by altering acceptor splice site at - 1 position affecting pre-mRNA splicing. These data confirm that the diverging splicing in the TGF-ß pathway genes may be an important process in aneurismal disease and emphasize the utility of genetic sequencing in the identification of high-risk patients for a more patient's management able to improve outcomes and minimize costs for the care of patients with heritable thoracic aortic aneurysm and dissection.

Cribado poblacional de aneurismas de la aorta abdominal. Estudio piloto en Salamanca / Population screening for abdominal aortic aneurysms. Pilot study in Salamanca

Introducción: una estrategia para reducir la mortalidad de los aneurismas de la aorta abdominal es conocer su existencia en fase asintomática. Así podremos clasificar los pacientes, en función del tamaño del aneurisma, en candidatos a cirugía programada o a seguimiento periódico. Objetivos: conocer la eficacia, la seguridad y la aceptabilidad de un programa piloto de cribado de aneurismas de la aorta abdominal mediante ecografía abdominal realizada en una población de riesgo. Material y métodos: programa organizado por la Real Academia de Medicina y el Instituto de Investigación Biomédica y ejecutado por el Servicio de Angiología, Cirugía Vascular y Endovascular del Hospital Universitario de Salamanca. El cribado se realizó hace un año, en dos carpas situadas en una céntrica plaza de Salamanca. El análisis incluyó a 295 varones ≥ 65 años, residentes en Salamanca capital, de forma libre y gratuita. Se excluyeron aquellos con aneurisma aórtico conocido. Se realizaron: 1) registro de datos; 2) eco Doppler color por especialistas en angiología y cirugía vascular, y 3) encuesta de satisfacción. Todos firmaron un consentimiento informado. Resultados: el diámetro transversal medio de la aorta abdominal fue de 1,81 ± 0,36 cm. Se detectaron 2 aneurismas (diámetro mayor: ≥ 3,0 cm; 3,1 y 4,7 cm) y 3 ectasias aórticas (diámetro ≥ 2,5 y < 3,0 cm). El 98,3 % (290 varones) no presentó ectasia o aneurisma (aorta < 2,5 cm). Tres individuos (obesidad o aire intrabdominal) fueron reevaluados posteriormente. Se analizaron los factores de riesgo y los antecedentes de la población cribada. 180 participantes del cribado (61,0 %) rellenaron anónimamente una encuesta de satisfacción, con resultados muy positivos. Conclusión: si bien el rendimiento de detección fue bajo, la estrategia y el método empleado fueron satisfactorios para el equipo explorador y la población explorada. Este estudio piloto nos permitirá planificar y organizar un segundo cribado más amplio y de nuevos objetivos.(AU)

Introduction: a strategy to reduce the mortality of abdominal aortic aneurysms is to know their existence in theasymptomatic phase. This way we can classify patients, mainly according to the size of the aneurysm, into candi-dates for scheduled elective surgery or periodic follow-up.Objectives: to determine the effectiveness, safety, and acceptability of a pilot screening program for abdominalaortic aneurysms, using abdominal ultrasound, performed in a risk population.Material and methods: program organized by the Royal Academy of Medicine and the Biomedical ResearchInstitute, and carried out by the Angiology and Vascular Surgery service of the University Hospital of Salamanca.The screening was carried out a year ago, in two tents located in a central square in Salamanca. The study included295 men over 65 years of age, residents of Salamanca capital, free of charge. Those with known aortic aneurysmwere excluded. The following were carried out: 1) data recording; 2) color echo-Doppler, by specialists in angiologyand vascular surgery; and 3) satisfaction survey. All signed an informed consent.Results: the mean transverse diameter of the abdominal aorta was 1.81 ± 0.36 cm. Two aneurysms were detect-ed (largest diameter ≥ 3.0 cm; 3.1 and 4.7 cm), and 3 aortic ectasias (diameter ≥ 2.5 and < 3.0 cm). The 98.3 %(290 men) did not present ectasia or aneurysm (aorta < 2.5 cm). Three individuals (obesity or intra-abdominal air) weresubsequently re-evaluated. The risk factors and background of the screened population were analyzed. A satisfactionsurvey was completed freely and anonymously by 180 screening participants (61.0 %) with very positive results.Conclusion: although the detection performance was low, the strategy and method used were satisfactory for theexploring team and the population explored. The present pilot study will allow us to plan and organize a second,broader screening with new objectives.(AU)

Modified upside-down technique with Gore tapered iliac limbs for isolated iliac artery aneurysms.

PURPOSE: To describe the off-label use of tapered iliac limbs for the treatment of isolated iliac aneurysms with proximal landing zone significantly larger than distal landing zone. TECHNIQUE: Inversion of a Gore Excluder tapered leg (W. L. Gore & Associates Inc, Flagstaff, Arizona) with a modified upside-down technique is described. The endoprosthesis, with the olive at the tip of the releasing system previously cut, is inserted in a tip-to-tip fashion into a 15 Fr introducer sheath. The graft is released inside the introducer. An 18 Fr introducer sheath is advanced up to the proximal sealing zone. Following the removal of the 18 Fr dilator, the 15 Fr introducer with the pre-released graft is inserted co-axially into the 18 Fr introducer. A pre-cut 15 Fr dilator is brought up to the endograft and used as a pusher. A pull-back maneuver of the co-axial system, countertractioning with the dilator maintained in position, allows the delivery of the endograft. CONCLUSION: This technique might offer a feasible option in case of endovascular exclusion of isolated iliac artery aneurysms with significant landing zone diameter mismatch. Extracorporeal inversion is time-saving and could be safer in terms of graft damage and infection.

Increasing abdominal aortic aneurysm curvature visibility using 3D dual probe bistatic ultrasound imaging combined with probe translation.

High frame rate ultrasound (US) imaging techniques in 3D are promising tools for capturing abdominal aortic aneurysms (AAAs) over time, however, with the limited number of channel-to-element connections current footprints are small, which limits the field of view. Moreover, the maximal steering angle of the ultrasound beams in transmit and the maximal receptance angle in receive are insufficient for capturing the curvy shape of the AAA. Therefore, an approach is needed towards large arrays. In this study, high frame rate bistatic 3D US data (17 Hz) were acquired with two synchronized matrix arrays positioned at different locations (multi-aperture imaging) using a translation stage to simulate what a larger array with limited channel-to-element connections can potentially achieve. Acquisitions were performed along an AAA shaped phantom with different probe tilting angles (0 up to ± 30°). The performance of different multi-aperture configurations was quantified using the generalized contrast-to-noise ratio of the wall and lumen (gCNR). Furthermore, a parametric model of the multi-aperture system was used to estimate in which AAA wall regions the contrast is expected to be high. This was evaluated for AAAs with increasing diameters and curvature. With an eight-aperture 0° probe angle configuration a 69 % increase in field of view was measured in the longitudinal direction compared to the field of view of a single aperture configuration. When increasing the number of apertures from two to eight, the gCNR improved for the upper wall and lower wall by 35 % and 13 % (monostatic) and by 36 % and 13 % (bistatic). Contrast improvements up to 22 % (upper wall) and 12 % (lower wall) are achieved with tilted probe configurations compared to non-tilted configurations. Moreover, with bistatic imaging with tilted probe configurations gCNR improvements up to 4 % (upper wall) and 7 % (lower wall) are achieved compared to monostatic imaging. Furthermore, imaging with a larger inter-probe distance improved the gCNR for a ± 15° probe angle configuration. The gCNR has an expected pattern over time, where the contrast is lower when there is more wall motion (systole) and higher when motion is reduced (diastole). Furthermore, a higher frame rate (45 Hz) yields a lower gCNR, because fewer compound angles are used. The results of the parametric model suggest that a flat array is suitable for imaging AAA shapes with limited curvature, but that it is not suitable for imaging larger AAA shapes with more curvature. According to the model, tilted multi-aperture configurations combined with bistatic imaging can achieve a larger region with high contrast compared to non-tilted configurations. The findings of the model are in agreement with experimental findings. To conclude, this study demonstrates the vast improvements in field of view and AAA wall visibility that a large, sparsely populated 3D array can potentially achieve when imaging AAAs compared to single or dual aperture imaging. In the future, larger arrays, less thermal noise, more steering, and more channel-to-element connections combined with carefully chosen orientations of (sub-) apertures will likely advance 3D imaging of AAAs.

The key role of miRNA in syndromic and sporadic forms of ascending aortic aneurysms as biomarkers and targets of novel therapeutic strategies.

Increasing evidence shows that epigenetics also plays a key role in regulating the pathogenetic mechanism of all types of aortic aneurysms. It is well-known that epigenetic factors modulate gene expression. This mechanism appears to be of interest especially knowing the relevance of genetic susceptibility and genetic factors in the complex pathophysiology of aortic aneurysms, and of sporadic forms; in fact, the latter are the result of a close interaction between genetic and modifiable lifestyle factors (i.e., nutrition, smoking, infections, use of drugs, alcohol, sedentary lifestyle, etc.). Epigenetic factors include DNA methylation, post-translational histone modifications, and non-coding RNA. Here, our attention is focused on the role of miRNA in syndromic and sporadic forms of thoracic aortic aneurysms. They could be both biomarkers and targets of novel therapeutic strategies.

Multi-Energy Low-Kiloelectron Volt versus Single-Energy Low-Kilovolt Images for Endoleak Detection at CT Angiography of the Aorta.

Purpose To compare image quality, diagnostic performance, and conspicuity between single-energy and multi-energy images for endoleak detection at CT angiography (CTA) after endovascular aortic repair (EVAR). Materials and Methods In this single-center prospective randomized controlled trial, individuals undergoing CTA after EVAR between August 2020 and May 2022 were allocated to imaging using either low-kilovolt single-energy images (SEI; 80 kV, group A) or low-kiloelectron volt virtual monoenergetic images (VMI) at 40 and 50 keV from multi-energy CT (80/Sn150 kV, group B). Scan protocols were dose matched (volume CT dose index: mean, 4.5 mGy ± 1.8 [SD] vs 4.7 mGy ± 1.3, P = .41). Contrast-to-noise ratio (CNR) was measured. Two expert radiologists established the reference standard for the presence of endoleaks. Detection and conspicuity of endoleaks and subjective image quality were assessed by two different blinded radiologists. Interreader agreement was calculated. Nonparametric statistical tests were used. Results A total of 125 participants (mean age, 76 years ± 8; 103 men) were allocated to groups A (n = 64) and B (n = 61). CNR was significantly lower for 40-keV VMI (mean, 19.1; P = .048) and 50-keV VMI (mean, 16.8; P < .001) as compared with SEI (mean, 22.2). In total, 45 endoleaks were present (A: 23 vs B: 22). Sensitivity for endoleak detection was higher for SEI (82.6%, 19 of 23; P = .88) and 50-keV VMI (81.8%, 18 of 22; P = .90) as compared with 40-keV VMI (77.3%, 17 of 22). Specificity was comparable among groups (SEI: 92.7%, 38 of 41; both VMI energies: 92.3%, 35 of 38; P = .99), with an interreader agreement of 1. Conspicuity of endoleaks was comparable between SEI (median, 2.99) and VMI (both energies: median, 2.87; P = .04). Overall subjective image quality was rated significantly higher for SEI (median, 4 [IQR, 4-4) as compared with 40 and 50 keV (both energies: median, 4 [IQR, 3-4]; P < .001). Conclusion SEI demonstrated higher image quality and comparable diagnostic accuracy as compared with 50-keV VMI for endoleak detection at CTA after EVAR. Keywords: Aneurysms, CT, CT Angiography, Vascular, Aorta, Technology Assessment, Multidetector CT, Abdominal Aortic Aneurysms, Endoleaks, Perigraft Leak Supplemental material is available for this article. © RSNA, 2024.

Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection.

Thoracic aortic aneurysms (TAAs) are a major cause of death owing to weaker blood vessel walls and higher rupture rates in affected individuals. Vascular smooth muscle cells (VSMCs) are the predominant cell type within the aortic wall and their dysregulation may contribute to TAA progression. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, is involved in several pathological processes; however, the biological functions and mechanisms underlying VSMC phenotype transition and vascular intimal hyperplasia remain unclear. The present study aimed to determine the involvement of EZH2 in mediating VSMC function in the development of TAAs. The expression of EZH2 was revealed to be elevated in patients with thoracic aortic dissection and TAA mouse model through western blotting and reverse transcription-quantitative PCR experiments. Subsequently, a mouse model was established using ß-aminopropionitrile. In vitro, EdU labeling, Transwell assay, wound healing assay and hematoxylin-eosin staining revealed that knocking down the Ezh2 gene could reduce the proliferation, invasion, migration, and calcification of mouse primary aortic smooth muscle cells. Flow cytometry analysis found that EZH2 deficiency increased cell apoptosis. Depletion of Ezh2 in mouse primary aortic VSMCs promoted the transformation of VSMCs from a synthetic to a contractile phenotype. Using RNA-sequencing analysis, it was demonstrated that Ezh2 regulated a group of genes, including integrin ß3 (Itgb3), which are critically involved in the extracellular matrix signaling pathway. qChIP found Ezh2 occupies the Itgb3 promoter, thereby suppressing the expression of Itgb3. Ezh2 promotes the invasion and calcification of VSMCs, and this promoting effect is partially reversed by co-knocking down Itgb3. In conclusion, the present study identified a previously unrecognized EZH2-ITGB3 regulatory axis and thus provides novel mechanistic insights into the pathophysiological function of EZH2. EZH2 may thus serve as a potential target for the management of TAAs.

[Development, techniques, and utility of experimental animal models of thoracic and abdominal aortic aneurysms]. / Desarrollo, técnicas y utilidad de modelos animales experimentales de aneurismas aórticos torácicos y abdominales.

Aneurysms are clinical entities that can develop and affect human aorta; and although in most cases they have an asymptomatic course, these pathological dilatations can lead to a lethal outcome when rupture occurs, thus the establishment of predictors is crucial for death prevention. Essential events that take place in the vessel wall have been identified and described, such as inflammation, proteolysis, smooth muscle cell apoptosis, angiogenesis, and vascular remodeling. Porcine and ovine models have been useful for the development and evaluation of endovascular devices of the aorta. However, since the worldwide introduction and adoption of these minimally invasive techniques for aneurysm repair, there is lesser availability of diseased aortic tissue for molecular, cellular, and histopathological analysis, therefore over the last three decades it has been proposed various small species models that have allowed the focal induction of these lesions for the study of physiopathological mechanisms and possible useful biomarkers as diagnostic and therapeutic targets. The present review article presents and discusses the animal models available as their applications, characteristics, advantages, and limitations for the development of preclinical studies, and their importance in the comprehension of this pathology in humans.

Los aneurismas son una de las entidades clínicas que pueden desarrollarse y afectar la aorta humana. Aunque en la mayoría de los casos tienen un carácter asintomático, estas dilataciones patológicas pueden resultar letales cuando se presentan con ruptura, por lo que el reconocimiento de factores predictores de esta complicación es crucial para evitar muertes. Fisiopatológicamente se han identificado eventos esenciales que ocurren en la pared del vaso, como inflamación, proteólisis, apoptosis del músculo liso, angiogénesis y remodelación. Las grandes especies como porcinos y ovinos han sido de utilidad para el desarrollo y evaluación del desempeño de dispositivos endovasculares en la aorta, así como la remodelación; con el advenimiento y disposición de estas técnicas mínimamente invasivas para su reparación existe una menor disponibilidad de tejido aórtico para el análisis molecular, celular e histopatológico, por lo que en las últimas tres décadas se han propuesto e introducido distintos modelos que han permitido, mediante la inducción focal de estas lesiones, el estudio de los mecanismos fisiopatológicos y posibles biomarcadores de utilidad como dianas diagnósticas y terapéuticas. El presente artículo de revisión aborda tipos de modelos animales disponibles, así como sus aplicaciones, consideraciones, ventajas y limitaciones para el desarrollo de estudios preclínicos y su importancia en el entendimiento de esta patología en la especie humana.

Four-dimensional flow cardiovascular magnetic resonance aortic cross-sectional pressure changes and their associations with flow patterns in health and ascending thoracic aortic aneurysm.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is a silent and threatening dilation of the ascending aorta (AscAo). Maximal aortic diameter which is currently used for ATAA patients management and surgery planning has been shown to inadequately characterize risk of dissection in a large proportion of patients. Our aim was to propose a comprehensive quantitative evaluation of aortic morphology and pressure-flow-wall associations from four-dimensional (4D) flow cardiovascular magnetic resonance (CMR) data in healthy aging and in patients with ATAA. METHODS: We studied 17 ATAA patients (64.7 ± 14.3 years, 5 females) along with 17 age- and sex-matched healthy controls (59.7 ± 13.3 years, 5 females) and 13 younger healthy subjects (33.5 ± 11.1 years, 4 females). All subjects underwent a CMR exam, including 4D flow and three-dimensional anatomical images of the aorta. This latter dataset was used for aortic morphology measurements, including AscAo maximal diameter (iDMAX) and volume, indexed to body surface area. 4D flow MRI data were used to estimate 1) cross-sectional local AscAo spatial (∆PS) and temporal (∆PT) pressure changes as well as the distance (∆DPS) and time duration (∆TPT) between local pressure peaks, 2) AscAo maximal wall shear stress (WSSMAX) at peak systole, and 3) AscAo flow vorticity amplitude (VMAX), duration (VFWHM), and eccentricity (VECC). RESULTS: Consistency of flow and pressure indices was demonstrated through their significant associations with AscAo iDMAX (WSSMAX:r = -0.49, p < 0.001; VECC:r = -0.29, p = 0.045; VFWHM:r = 0.48, p < 0.001; ∆DPS:r = 0.37, p = 0.010; ∆TPT:r = -0.52, p < 0.001) and indexed volume (WSSMAX:r = -0.63, VECC:r = -0.51, VFWHM:r = 0.53, ∆DPS:r = 0.54, ∆TPT:r = -0.63, p < 0.001 for all). Intra-AscAo cross-sectional pressure difference, ∆PS, was significantly and positively associated with both VMAX (r = 0.55, p = 0.002) and WSSMAX (r = 0.59, p < 0.001) in the 30 healthy subjects (48.3 ± 18.0 years). Associations remained significant after adjustment for iDMAX, age, and systolic blood pressure. Superimposition of ATAA patients to normal aging trends between ∆PS and WSSMAX as well as VMAX allowed identifying patients with substantially high pressure differences concomitant with AscAo dilation. CONCLUSION: Local variations in pressures within ascending aortic cross-sections derived from 4D flow MRI were associated with flow changes, as quantified by vorticity, and with stress exerted by blood on the aortic wall, as quantified by wall shear stress. Such flow-wall and pressure interactions might help for the identification of at-risk patients.

Survival, Short And Long-Term Outcomes Of Open And Endovascular Surgical Repair Of Unruptured Infrarenal Abdominal Aortic Aneurysms.

INTRODUCTION: Endovascular Aortic Repair (EVAR) has become the standard management of Unruptured Infrarenal Abdominal Aortic Aneurysm (UIAAA); however, current evidence is limited and uncertain in our environment compared to Open repair. Our study aimed to determine the survival, short and long-term outcomes of EVAR vs. Open in a Peruvian cohort of UIAAA. METHODS: A single-center observational, analytical, longitudinal study using a retrospective registry of 251 patients treated (EVAR=205 vs Open=46) for UIAAA from 2000 to 2017. Variables considered were baseline, comorbidities, type of treatment, short-term (<30 days) and long-term (<5 years) outcomes, postoperative mortality according to the Vascular Quality Initiative (VQI) Risk Score, survival curves including reoperation-free rate and according to size (<65 mm vs. >65 mm) of long-term UIAAA. All variables were grouped according to the treatment performed (EVAR vs. Open) and we used the descriptive, multivariate, Cox regression, and Kaplan-Meier survival statistical analyses. RESULTS: 251 UIAAA were evaluated and the mean age was 74.5 years [±13.32], smoking, family members with UIAAA, and previous abdominal surgery were the main antecedents. Diabetes mellitus 2 was the main comorbidity; more than 50% of patients with UIAAA had diameters greater than 65 mm (p=0.021). The calculated mortality (VQI) was Open=2.21% vs. EVAR=1.65%. The outcomes in short-term were mortality (Open=2.92% vs. EVAR=0%; p=0.039), blood transfusion >4 Units (Open=72.68% vs. EVAR=17.39%; p=0.021) and overall hospital stay (Open=14 vs. EVAR=5 days; p=0.049. A reduction in mortality (HR 0.76, 95% CI, 0.62-0.96, p=0.045) and readmission for aneurysmal rupture was identified for EVAR (HR 0.81, 95% CI, 0.79-0.85, p=0.031). In long-term outcomes, mortality (Open=3.41% vs. EVAR=19.56%; p=0.047), aneurysmal rupture (Open=0% vs. EVAR 13.04%; p=0.032) and reinterventions (Open=2.43% vs. EVAR=10.86%; p=0.002). An 86% risk of mortality (HR 1.86, 95% CI, 1.32-2.38, p=0.039) and elevated risk of readmission for aneurysmal rupture was identified for EVAR (HR 2.21, 95% CI, 1.98-2.45, p=0.028). At 5 years, survival for Open=93.67% vs. EVAR=80.44% (p=0.043), reintervention-free survival for Open=89.26% vs. EVAR=47.82% (p=0.021), survival for treated IUAAA <65 mm for Open=95.77% vs. EVAR=63.63% (p=0.019) and >65 mm for Open=92.53% vs. EVAR=85.71% (p=0.059). CONCLUSION: EVAR has shown better short-term benefits and survival than Open management; however, the latter still prevails in the long term in our Peruvian UIAAA cohort. Further follow-up studies are required to demonstrate the long-term benefit of EVAR in our population.

Emerging roles for the ADAMTS-like family of matricellular proteins in cardiovascular disease through regulation of the extracellular microenvironment.

Dysregulation of the extracellular matrix (ECM) occurs widely across cardiovascular pathologies. Recent work has revealed important roles for the «a disintegrin-like and metalloprotease domain with thrombospondin-type 1 motifs like" (ADAMTSL) family of secreted glycoproteins in cardiovascular tissues during development and disease. Key insights in this regard have come from naturally occurring gene mutations in humans and animals that result in severe diseases with cardiovascular manifestations or aortopathies. Expression of ADAMTSL genes is greatly increased in the myocardium during heart failure. Genetically modified mice recapitulate phenotypes of patients with ADAMTSL mutations and demonstrate important functions in the ECM. The novel functions thus disclosed are intriguing because, while these proteins are neither structural, nor proteases like the related ADAMTS proteases, they appear to act as regulatory, i.e., matricellular proteins. Evidence from genetic variants, genetically engineered mouse mutants, and in vitro investigations have revealed regulatory functions of ADAMTSLs related to fibrillin microfibrils and growth factor signaling. Interestingly, the ability to regulate transforming growth factor (TGF)ß signaling may be a shared characteristic of some ADAMTSLs. TGFß signaling is important in cardiovascular development, health and disease and a central driver of ECM remodeling and cardiac fibrosis. New strategies to target dysregulated TGFß signaling are warranted in aortopathies and cardiac fibrosis. With their emerging roles in cardiovascular tissues, the ADAMTSL proteins may provide causative genes, diagnostic biomarkers and novel treatment targets in cardiovascular disease. Here, we discuss the relevance of ADAMTSLs to cardiovascular medicine.

Enhanced visualization in endoleak detection through iterative and AI-noise optimized spectral reconstructions.

To assess the image quality parameters of dual-energy computed tomography angiography (DECTA) 40-, and 60 keV virtual monoenergetic images (VMIs) combined with deep learning-based image reconstruction model (DLM) and iterative reconstructions (IR). CT scans of 28 post EVAR patients were enrolled. The 60 s delayed phase of DECTA was evaluated. Objective [noise, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR)] and subjective (overall image quality and endoleak conspicuity - 3 blinded readers assessment) image quality analyses were performed. The following reconstructions were evaluated: VMI 40, 60 keV VMI; IR VMI 40, 60 keV; DLM VMI 40, 60 keV. The noise level of the DLM VMI images was approximately 50% lower than that of VMI reconstruction. The highest CNR and SNR values were measured in VMI DLM images. The mean CNR in endoleak in 40 keV was accounted for as 1.83 ± 1.2; 2.07 ± 2.02; 3.6 ± 3.26 in VMI, VMI IR, and VMI DLM, respectively. The DLM algorithm significantly reduced noise and increased lesion conspicuity, resulting in higher objective and subjective image quality compared to other reconstruction techniques. The application of DLM algorithms to low-energy VMIs significantly enhances the diagnostic value of DECTA in evaluating endoleaks. DLM reconstructions surpass traditional VMIs and IR in terms of image quality.

Genetic Association of Lipid-Lowering Drugs with Aortic Aneurysms: A Mendelian Randomization Study.

AIMS: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA. METHODS: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. RESULTS: The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, p = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, p = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, p = 1.78 × 10-04). PCSK9 (Proprotein convertase subtilisin/kexin type 9) and CETP (Cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, p = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, p = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA. CONCLUSIONS: This study provides causal evidence for the genetic association between lipid-lowering drugs and aortic aneurysms. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.

This Mendelian Randomization study used publicly available data involving over 1 million individuals to demonstrate the causal relationship between five target genes of LDL-C-lowering medicines and the risk of aortic aneurysms, and implied one lipid-lowering drug may link with the lumen size of aortic aneurysms. Key findings High expression of HMGCR, PCSK9, and CETP was positively correlated with the risk of aortic aneurysms, highlighting that the corresponding lipid-lowering drugs may be preferred for preventing arterial aneurysms in high-risk individuals with dyslipidemia. We found that genetically predicted HMGCR inhibitors were positively associated with smaller aortic lumen size, which is the first time to support the causal association of gene HMGCR on the lumen size of aortic aneurysms.

Diagnosis and treatment of cardiovascular disease in patients with heritable connective tissue disorders or heritable thoracic aortic diseases.

Patients with heritable connective tissue disorders (HCTDs), represented by Marfan syndrome, can develop fatal aortic and/or arterial complications before age 50. Therefore, accurate diagnosis, appropriate medical treatment, and early prophylactic surgical treatment of aortic and arterial lesions are essential to improve prognosis. Patients with HCTDs generally present with specific physical features due to connective tissue abnormalities, while some patients with heritable thoracic aortic diseases (HTADs) have few distinctive physical characteristics. The development of genetic testing has made it possible to provide accurate diagnoses for patients with HCTDs/HTADs. This review provides an overview of the diagnosis and treatment of HCTDs/HTADs, including current evidence on cardiovascular interventions for this population.

Preoperative proteinuria is independently associated with mortality after fenestrated endovascular aneurysm repair.

OBJECTIVE: Fenestrated endovascular aneurysm repair (FEVAR) has become a mainstay in treating complex aortic aneurysms, though baseline patient factors predicting long-term outcomes remain poorly understood. Proteinuria is an early marker for chronic kidney disease and associated with adverse cardiovascular outcomes, but its utility in patients with aortic aneurysms is unknown. We aimed to determine whether preoperative proteinuria impacts long-term survival after FEVAR. METHODS: A single-institution, retrospective review of all elective FEVAR was performed. Preoperative proteinuria was assessed by urinalysis: negative (0-29 mg/dL), 1+ (30-100 mg/dL), 2+ (101-299 mg/dL), and 3+ (≥300 mg/dL). The cohort was stratified by patients with proteinuria (≥30 mg/dL) vs those without (<30 mg/dL). Baseline, perioperative, and long-term outcomes were compared. The primary outcome, all-cause mortality, was evaluated by Kaplan-Meier analysis and independent predictors with Cox proportional hazards modeling. RESULTS: Among 181 patients who underwent standard FEVAR from 2012 to 2022 (mean follow-up 33 months), any proteinuria was noted in 30 patients (16.6%). Patients with proteinuria were more likely to be Black (10.0% vs 1.3%) with a lower estimated glomerular filtration rate (eGFR) (52.7 ± 24.7 vs 67.7 ± 20.5 mL/min/1.73 m2), higher Society for Vascular Surgery comorbidity score (10.9 ± 4.3 vs 8.2 ± 4.7) and calcium channel blocker therapy (50.0% vs 29.1%), and larger maximal aneurysm diameter (67.2 ± 16.9 vs 59.8 ± 9.8 mm) (all P < .05). Thirty-day mortality was higher in the proteinuria group (10.0% vs 1.3%; P = .03). Overall survival at 1 and 5 years was significantly lower for those with proteinuria (71.5% vs 92.3% and 29.5% vs 68.1%; log-rank P < .001). On multivariable analysis, preoperative proteinuria was independently associated with over threefold higher hazard of mortality (hazard ratio [HR]: 3.21, 95% confidence interval [CI]: 1.66-6.20; P < .001), whereas preoperative eGFR was not predictive (HR: 0.99, 95% CI: 0.98-1.01; P = .28). Additional significant predictors included chronic obstructive pulmonary disease (HR: 2.04), older age (HR: 1.05), and larger maximal aneurysm diameter (HR: 1.03; all P < .05). CONCLUSIONS: In our 10-year experience with FEVAR, preoperative proteinuria was observed in 17% of patients and was significantly associated with worse survival. In this cohort, proteinuria was independently associated with all-cause mortality, whereas eGFR was not, suggesting that urinalysis may provide an additional simple metric for risk-stratifying patients before FEVAR.