Giant unruptured sinus of Valsalva aneurysms causing angina pectoris.

BACKGROUND: Sinus of Valsalva aneurysm (SVA) is a rare cardiac anomaly which can be congenital or acquired. Patients with SVA are commonly asymptomatic when the occupying effect of SVA is insignificant, while ruptured SVA usually causes severe symptoms including heart failure and myocardial ischemia. CASE PRESENTATION: We present an unusual case of a 64-year-old female manifesting with exertional dyspnea as well as angina pectoris for three months. Echocardiography and cardiac computed tomographic angiography confirmed unruptured left-coronary and non-coronary SVAs. The left anterior descending artery and left circumflex artery were stretched and compressed by the SVA which causing myocardial ischemia. The patient finally received aortic root replacement (Bentall procedure) and got symptom relieved. CONCLUSIONS: Giant unruptured SVA originating from left coronary sinus is extremely rare. Our case highlights that giant SVA should be considered in cases with angina pectoris. Echocardiography and coronary computed tomographic angiography are useful and important for diagnosis. Surgery is highly recommended in patients with SVA.

A visceral organ function-focused therapeutic strategy using a 6-hour time window for patients with acute type a aortic dissection complicated by mesenteric malperfusion.

BACKGROUND: Acute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion. METHODS: This was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h. RESULTS: There were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences. CONCLUSIONS: Our novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate.

Exploiting light-based 3D-printing for the fabrication of mechanically enhanced, patient-specific aortic grafts.

Despite polyester vascular grafts being routinely used in life-saving aortic aneurysm surgeries, they are less compliant than the healthy, native human aorta. This mismatch in mechanical behaviour has been associated with disruption of haemodynamics contributing to several long-term cardiovascular complications. Moreover, current fabrication approaches mean that opportunities to personalise grafts to the individual anatomical features are limited. Various modifications to graft design have been investigated to overcome such limitations; yet optimal graft functionality remains to be achieved. This study reports on the development and characterisation of an alternative vascular graft material. An alginate:PEGDA (AL:PE) interpenetrating polymer network (IPN) hydrogel has been produced with uniaxial tensile tests revealing similar strength and stiffness (0.39 ± 0.05 MPa and 1.61 ± 0.19 MPa, respectively) to the human aorta. Moreover, AL:PE tubular conduits of similar geometrical dimensions to segments of the aorta were produced, either via conventional moulding methods or stereolithography (SLA) 3D-printing. While both fabrication methods successfully demonstrated AL:PE hydrogel production, SLA 3D-printing was more easily adaptable to the fabrication of complex structures without the need of specific moulds or further post-processing. Additionally, most 3D-printed AL:PE hydrogel tubular conduits sustained, without failure, compression up to 50% their outer diameter and returned to their original shape upon load removal, thereby exhibiting promising behaviour that could withstand pulsatile pressure in vivo. Overall, these results suggest that this AL:PE IPN hydrogel formulation in combination with 3D-printing, has great potential for accelerating progress towards personalised and mechanically-matched aortic grafts.

Unicommissural unicuspid aortic valve (UAV) presenting as ascending aortic aneurysm with aortic dissection.

We herein present an exceptionally rare instance of a unicommissural unicuspid aortic valve (UAV) manifesting with an aneurysmal ascending aorta complicated by a type A aortic dissection .

Region-specific delamination strength of ascending thoracic aortic aneurysm of elderly hypertensive patients with bicuspid and tricuspid aortic valves.

Both ageing and hypertension are clinical factors that may lead to a higher propensity for dissection or rupture of ascending thoracic aortic aneurysms (ATAAs). This study sought to investigate effect of valve morphology on regional delamination strength of ATAAs in the elderly hypertensive patients. Whole fresh ATAA samples were harvested from 23 hypertensive patients (age, 71 ± 8 years) who underwent elective aortic surgery. Peeling tests were performed to measure region-specific delamination strengths of the ATAAs, which were compared between patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). The regional delamination strengths of the ATAAs were further correlated with patient ages and aortic diameters for BAV and TAV groups. In the anterior and right lateral regions, the longitudinal delamination strengths of the ATAAs were statistically significantly higher for BAV patients than TAV patients (33 ± 7 vs. 23 ± 8 mN/mm, p = 0.01; 30 ± 7 vs. 19 ± 9 mN/mm, p = 0.02). For both BAV and TAV patients, the left lateral region exhibited significantly higher delamination strengths in both directions than the right lateral region. Histology revealed that disruption of elastic fibers in the right lateral region of the ATAAs was more severe for the TAV patients than the BAV patients. A strong inverse correlation between longitudinal delamination strength and age was identified in the right lateral region of the ATAAs of the TAV patients. Results suggest that TAV-ATAAs are more vulnerable to aortic dissection than BAV-ATAAs for the elderly hypertensive patients. Regardless of valve morphotypes, the right lateral region may be a special quadrant which is more likely to initiate dissection when compared with other regions.

Hybrid noncovered open stents in repair of DeBakey type 1 acute aortic dissections.

OBJECTIVES: The indications for use, evidence base and experience with the novel noncovered open hybrid surgical stents for acute type A aortic dissection repair for concurrent stabilization of the 'downstream' aorta remains limited. We review the evidence base and the development of these stents. METHODS: Data were collected from Pubmed/Medline literature search to develop and review the evidence base for safety and efficacy of non-covered surgical stents. Existing guidelines for use and developments were reviewed. RESULTS: A single randomized control trial and 4 single-centre studies were included in the review with a total worldwide experience of 241 patients. The deployment was easy and did not add significantly to the primary operation. The mortality and new stroke ranged from 6.3-18.7%. Safe and complete deployment was accomplished in 92-100%. There was no device-related reintervention. There was a significant improvement in malperfusion in over 90% of the cases with varying degrees of remodelling (60-90%) of the downstream aorta. CONCLUSIONS: Open noncovered stent grafts represent a major technical advancement as an adjunct procedure for acute dissection repairs, e.g. hemiarch repair. It has potential for wider use by non-aortic surgeons due to simplicity of technique. Limited safety and efficacy data confirm the device to be safe, feasible and reproducible with potential for wider adoption. However, long-term trial and registry data are required before recommendations for standard use outside of high-volume experienced aortic centres.

Safety of fluoroquinolones / Seguridad de las fluoroquinolonas

Fluoroquinolones (FQs) are one of the most commonly prescribed classes of antibiotics. Although they were initially well tolerated in randomized clinical trials, subsequent epidemiological studies have reported an increased risk of threatening, severe, long-lasting, disabling and irreversible adverse effects (AEs), related to neurotoxicity and collagen degradation, such as tendonitis, Achilles tendon rupture, aortic aneurysm, and retinal detachment. This article reviews the main potentially threatening AEs, the alarms issued by regulatory agencies and therapeutic alternatives. (AU)

Las fluoroquinolonas son una de las clases de antibióticos más prescritas. Aunque inicialmente fueron bien toleradas en ensayos clínicos aleatorizados, estudios epidemiológicos posteriores han informado de un mayor riesgo de efectos adversos efectos adversos amenazantes, graves, duraderos, incapacitantes e irreversibles, relacionados con la neurotoxicidad y la degradación del colágeno, como tendinitis, rotura del tendón de Aquiles, aneurisma aórtico y desprendimiento de retina. Este artículo repasa los principales efectos adversos potencialmente amenazadores, las alarmas emitidas por las agencias reguladoras y las alternativas terapéuticas. (AU)

Aorto-atrial tunnel arising from sinus of Valsalva aneurysm in a young female.

A young female patient presented with complaints of breathlessness and palpitations since 2 years. On clinical examination, there was a loud continuous murmur at the right sternal border.Transthoracic echocardiography and colour Doppler showed a tunnel-like structure originating from the aneurysmal right coronary sinus and opening into the right atrium with left to right shunt. Coronary angiography revealed a large tunnel beginning in right coronary sinus and terminating in the right atrium and right coronary artery (RCA) was seen originating from the tunnel. Cardiac catheterisation revealed normal pulmonary artery pressure. CT and 3D-reconstructed images delineated the extracardiac course of the tunnel.Various treatment modalities including percutaneous transcatheter approach and surgical treatment were taken into consideration, but because of the close proximity of RCA from the tunnel opening, surgical closure was preferred.

Heritable thoracic aortic disease: a literature review on genetic aortopathies and current surgical management.

Heritable thoracic aortic disease puts patients at risk for aortic aneurysms, rupture, and dissections. The diagnosis and management of this heterogenous patient population continues to evolve. Last year, the American Heart Association/American College of Cardiology Joint Committee published diagnosis and management guidelines for aortic disease, which included those with genetic aortopathies. Additionally, evolving research studying the implications of underlying genetic aberrations with new genetic testing continues to become available. In this review, we evaluate the current literature surrounding the diagnosis and management of heritable thoracic aortic disease, as well as novel therapeutic approaches and future directions of research.

Liraglutide attenuates angiotensin II-induced aortic dissection and aortic aneurysm via inhibiting M1 macrophage polarization in APOE -/- mice.

BACKGROUND: Aortic Aneurysm and Dissection (AAD) are severe cardiovascular conditions with potentially lethal consequences such as aortic rupture. Existing studies suggest that liraglutide, a long-acting glucagon-like peptide receptor (GLP-1R) agonist, offers protective benefits across various cardiovascular diseases. However, the efficacy of liraglutide in mitigating AAD development is yet to be definitively elucidated. METHODS: Ang II (Angiotension II) infusion of APOE-/- mouse model with intraperitoneal injection of liraglutide (200 µg/kg) to study the role of GLP-1R in AAD formation. Bone Marrow Derived Macrophages (BMDM) and Raw264.7 were incubated with LPS, liraglutide, exendin 9-39 or LY294002 alone or in combination. SMC phenotype switching was examined in a macrophage and vascular smooth muscle cell (VSMC) co-culture system. An array of analytical methods, including Western Blot, Immunofluorescence Staining, Enzyme-LinkedImmunosorbent Assay, Real-Time Quantitative Polymerase Chain Reaction, RNA-seq, and so on were employed. RESULTS: Our investigation revealed a significant increase in M1 macrophage polarization and GLP-1R expression in aortas of AD patients and Ang II-induced AAD APOE-/- mice. Administering liraglutide in APOE-/- mice notably reduced Ang II-induced AAD incidence and mortality. It was found that liraglutide inhibits M1 macrophage polarization primarily via GLP-1R activation, and subsequently modulates vascular smooth muscle cell phenotypic switching was the primary mechanism. RNA-Seq and subsequent KEGG enrichment analysis identified CXCL3, regulated by the PI3K/AKT signaling pathway, as a key element in liraglutide's modulation of M1 macrophage polarization. CONCLUSION: Our study found liraglutide exhibits protective effects against AAD by modulating M1 macrophage polarization, suppressing CXCL3 expression through the PI3K/AKT signaling pathway. This makes it a promising therapeutic target for AAD, offering a new avenue in AAD management.

Mendelian randomization study on insulin resistance and risk of hypertension and cardiovascular disease.

Observational studies have suggested that insulin resistance (IR) is associated with hypertension and various cardiovascular diseases. However, the presence of a causal relationship between IR and cardiovascular disease remains unclear. Here, we applied Mendelian randomization (MR) approaches to address the causal association between genetically determined IR and the risk of cardiovascular diseases. Our primary genetic instruments comprised 53 SNPs associated with IR phenotype from a GWAS of up to 188,577 participants. Genetic association estimates for hypertension and venous thromboembolism (VTE) were extracted from UK Biobank, estimates for atrial fibrillation (AF) were extracted from the hitherto largest GWAS meta-analysis on AF, estimates for heart failure were extracted from HERMES Consortium, estimates for peripheral artery disease (PAD) and aortic aneurysm were extracted from the FinnGen Study. The main analyses were performed using the random-effects inverse-variance weighted approach, and complemented by sensitivity analyses and multivariable MR analyses. Corresponding to 55% higher fasting insulin adjusted for body mass index, 0.46 mmol/L lower high-density lipoprotein cholesterol and 0.89 mmol/L higher triglyceride, one standard deviation change in genetically predicted IR was associated with increased risk of hypertension (odds ratio (OR) 1.06, 95% CI 1.04-1.08; P = 1.91 × 10-11) and PAD (OR 1.90, 95% CI 1.43-2.54; P = 1.19 × 10-5). Suggestive evidence was obtained for an association between IR and heart failure (OR per SD change in IR: 1.19, 95% CI 1.01-1.41, P = 0.041). There was no MR evidence for an association between genetically predicted IR and atrial fibrillation, VTE, and aortic aneurysm. Results were widely consistent across all sensitivity analyses. In multivariable MR, the association between IR and PAD was attenuated after adjustment for lipids (P = 0.347) or BMI (P = 0.163). Our findings support that genetically determined IR increases the risk of hypertension and PAD.

Significant thrombus in saccular aneurysm in a patient with polycythemia: a case report.

BACKGROUND: Morphologically, the risk of aortic aneurysm rupture is mainly evaluated based on its type (e.g., fusiform or saccular) and diameter. Based on the finite element analysis, peak wall stress has been identified as a more sensitive and specific predictor of rupture in recent years. Moreover, in finite analysis, the neck of aneurysm is the highest peak wall stress and is associated with the rupture point. CASE PRESENTATION: A saccular aortic aneurysm (84 mm) was incidentally detected during preoperative examination for chronic empyema in a 74-year-old male patient with a history of polycythemia. Aortic arch graft replacement using an open stent was performed. CONCLUSIONS: Morphologically, this case was associated with a very high risk of rupture; nevertheless, it did not rupture. In this case, a mural thrombus (likely formed due to polycythemia) covered the neck of aneurysm that is experiencing the highest peak wall stress and is associated with the rupture point. The mural thrombus decreased peak wall stress and could reduce the risk of rupture even for huge saccular aneurysms. Furthermore, the mural thrombus was fully occupied in aneurysms, such as during coil embolization. Thus, polycythemia could decrease the risk of rupture of huge saccular aneurysms.

Histone deacetylase 9-mediated phenotypic transformation of vascular smooth muscle cells is a potential target for treating aortic aneurysm/dissection.

Aortic aneurysm/dissection (AAD) is a serious cardiovascular condition characterized by rapid onset and high mortality rates. Currently, no effective drug treatment options are known for AAD. AAD pathogenesis is associated with the phenotypic transformation and abnormal proliferation of vascular smooth muscle cells (VSMCs). However, endogenous factors that contribute to AAD progression remain unclear. We aimed to investigate the role of histone deacetylase 9 (HDAC9) in AAD pathogenesis. HDAC9 expression was considerably increased in human thoracic aortic dissection specimens. Using RNA-sequencing (RNA-seq) and chromatin immunoprecipitation, we demonstrated that HDAC9 transcriptionally inhibited the expression of superoxide dismutase 2 and insulin-like growth factor-binding protein-3, which are critically involved in various signaling pathways. Furthermore, HDAC9 triggered the transformation of VSMCs from a systolic to synthetic phenotype, increasing their proliferation and migration abilities and suppressing their apoptosis. Consistent with these results, in vivo experiments revealed that TMP195, a pharmacological inhibitor of HDAC9, suppressed the formation of the ß-aminopropionitrile-induced AAD phenotype in mice. Our findings indicate that HDAC9 may be a novel endogenous risk factor that promotes the onset of AAD by mediating the phenotypic transformation of VSMCs. Therefore, HDAC9 may serve as a potential therapeutic target for drug-based AAD treatment. Furthermore, TMP195 holds potential as a therapeutic agent for AAD treatment.

Successful endovascular treatment of aortic arch aneurysm in a pediatric patient.

BACKGROUND: Ascending aortic aneurysms are rare pathologies in childhood, especially in the absence of previous diseases such as Marfan syndrome. OBJECTIVE: Present the possibility of successful endovascular management of large vessel aneurysms, using stents and microcatheters with embolization of the aneurysm sac. METHOD: We present the case of a previously healthy ten-year-old patient, in whom a pseudoaneurysm was documented between the origin of the left common carotid artery and left subclavian artery, successfully managed endovascularly, initially with a stent covering the neck of the aneurysm to remodel it and later with embolization of the aneurysm sac using a microcatheter. RESULTS: Aneurysms of large vessels, such common carotid artery and subclavian artery, are at risk of rupture with devastating complications; endovascular management is considered a minimally invasive management option, with favorable results. CONCLUSION: The endovascular management of large vessel aneurysms using stents and microcatheters with embolization of the aneurysmal sac is a novel management option that achieves successful results.

ANTECEDENTES: Los aneurismas de la aorta ascendente son patologías poco frecuentes en la infancia, sobre todo en ausencia de enfermedades previas como el síndrome de Marfan. OBJETIVO: Dar a conocer la posibilidad del manejo endovascular exitoso de los aneurismas de grandes vasos, usando stent y micro catéter con embolización del saco aneurismático. MÉTODO: Presentamos el caso de una paciente de 10 años y 2 meses, previamente sana, en quien se documentó un pseudoaneurisma entre el origen de la arteria carótida común izquierda y la arteria subclavia izquierda, que logró manejarse de forma endovascular, inicialmente con un stent cubriendo el cuello del aneurisma con el fin de remodelarlo y posteriormente por medio de microcatéter se realizó embolización del saco del aneurisma con coils, con resultado exitoso. RESULTADOS: Los aneurismas de los grandes vasos, como la arteria carótida común y la arteria subclavia, tienen riesgo de ruptura con complicaciones devastadoras; el manejo endovascular se plantea como una opción poco invasiva de manejo, con resultados favorables. CONCLUSIÓN: El manejo de aneurismas de grandes vasos, por vía endovascular usando stent y microcatéter con embolización del saco aneurismático, es una opción novedosa de manejo que logra resultados exitosos.

Diameter and dissection of the abdominal aorta and the risk of distal aortic reoperation after surgery for type A aortic dissection.

BACKGROUND: Surgery for Stanford type A aortic dissection (TAAD) is associated with an increased risk of late aortic reoperations due to degeneration of the dissected aorta. METHODS: The subjects of this analysis were 990 TAAD patients who survived surgery for acute TAAD and had complete data on the diameter and dissection status of all aortic segments. RESULTS: After a mean follow-up of 4.2 ± 3.6 years, 60 patients underwent 85 distal aortic reoperations. Ten-year cumulative incidence of distal aortic reoperation was 9.6%. Multivariable competing risk analysis showed that the maximum preoperative diameter of the abdominal aorta (SHR 1.041, 95%CI 1.008-1.075), abdominal aorta dissection (SHR 2.133, 95%CI 1.156-3.937) and genetic syndromes (SHR 2.840, 95%CI 1.001-8.060) were independent predictors of distal aortic reoperation. Patients with a maximum diameter of the abdominal aorta >30 mm and/or abdominal aortic dissection had a cumulative incidence of 10-year distal aortic reoperation of 12.0% compared to 5.7% in those without these risk factors (adjusted SHR 2.076, 95%CI 1.062-4.060). CONCLUSION: TAAD patients with genetic syndromes, and increased size and dissection of the abdominal aorta have an increased the risk of distal aortic reoperations. A policy of extensive surgical or hybrid primary aortic repair, completion endovascular procedures for aortic remodeling and tight surveillance may be justified in these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04831073.

Coarctation of Aorta With Tricuspid Aortic Valve Is Not Associated With Ascending Aortic Aneurysm.

BACKGROUND: Aortic aneurysm is common in patients with coarctation of aorta (COA), but it is unclear whether the risk of aortic aneurysms is due to COA or related to the presence of other risk factors such as bicuspid aortic valve (BAV) and hypertension. OBJECTIVES: The purpose of this study was to assess the relationship among COA, BAV, and thoracic aortic aneurysms. METHODS: A total of 867 patients with COA (COA group) were matched 1:1:1 to 867 patients with isolated BAV (BAV group) and 867 patients without structural heart disease (SHD) (no-SHD group). The COA group was further subdivided into a COA+BAV subgroup (n = 304 [35%]), and COA with tricuspid aortic valve (TAV) (COA+TAV subgroup [n = 563 (65%)]). Aortic dimensions were assessed at baseline and at 3, 5, and 7 years. RESULTS: Compared with the no-SHD group, the COA+BAV subgroup had larger aortic root diameter (37 mm [Q1-Q3: 30-43 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001) and mid ascending aorta dimeter (34 mm [Q1-Q3: 29-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P = 0.008). Similarly, the BAV group had larger aortic root diameter (37 mm [Q1-Q3: 30-42 mm] vs 32 mm [Q1-Q3: 27-35 mm]; P < 0.001), and mid ascending aorta dimeter (35 mm [Q1-Q3: 30-40 mm] vs 28 mm [Q1-Q3: 24-31 mm]; P < 0.001). Compared with the COA+TAV subgroup, the COA+BAV subgroup and BAV group were associated with larger aortic root and mid ascending aorta diameter at baseline and follow-up. The risk of acute aortic complications was low in all groups. CONCLUSIONS: These findings suggest that BAV (and not COA) was associated with ascending thoracic aorta dimensions, and that patients with COA+TAV were not at a greater risk of developing ascending aortic aneurysms as compared with patients without SHD.

Later aorta operation after aortic valve replacement for bicuspid aortic valve.

BACKGROUND: We investigated long-term outcomes, particularly later aorta operations and overall death in patients who underwent aortic valve replacement for bicuspid aortic valve without aortic surgery. METHODS: Between January 2002 and December 2022, 274 patients underwent aortic valve replacement for bicuspid aortic valve at our institution. Of them, 181 patients who did not undergo aortic surgery, in accordance with current guidelines, were analyzed retrospectively. RESULTS: The median follow-up duration was 6.1 (2.0-10.6) years, and follow-up was completed in 97.8% of pateints. There were 3 patients (1.7%) who underwent later aorta operation during follow-up period. The cumulative later aorta operation rate at 10 years adjusting overall death as competing risk was 16.3%, and the estimated rates of freedom from overall death at 10 years was 83.7%. Fine-Gray competing risk regression model showed that aortic valve stenosis was only the predictor of later aorta operation (hazard ratio 8.477; p = 0.012). In multivariable Cox models, predictors of overall death were aortic valve stenosis (hazard ratio: 8.270, 95% confidence interval: 1.082-63.235; p = 0.042) and operation time (hazard ratio: 1.011, 95% confidence interval: 1.004-1.017; p = 0.002). CONCLUSIONS: Patients with bicuspid aortic valve with ascending aortic diameter less than 45 mm are at low risk of later aorta operation after isolated aortic valve replacement.

Right Sinus of Valsalva Aneurysm Rupturing into the Right Atrium and Dissecting into the Interventricular Septum.

The right sinus of the Valsalva aneurysm (SVA) rupturing into the right atrium (RA) and dissecting into the interventricular septum (IVS) is rare. The disease can be definitively diagnosed using two-dimensional (2D) echocardiography and color Doppler ultrasonography. Real-time biplane imaging and three-dimensional (3D) echocardiography offer new perspectives for viewing and diagnosing this disease.