Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization.

BACKGROUND: In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. MATERIALS AND METHODS: We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. RESULTS: The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836-0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12-44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607-0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. CONCLUSION: Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated.

Investigation of Strategies to Block Downstream Effectors of AT1R-Mediated Signalling to Prevent Aneurysm Formation in Marfan Syndrome.

Cardiovascular outcome in Marfan syndrome (MFS) patients most prominently depends on aortic aneurysm progression with subsequent aortic dissection. Angiotensin II receptor blockers (ARBs) prevent aneurysm formation in MFS mouse models. In patients, ARBs only slow down aortic dilation. Downstream signalling from the angiotensin II type 1 receptor (AT1R) is mediated by G proteins and ß-arrestin recruitment. AT1R also interacts with the monocyte chemoattractant protein-1 (MCP-1) receptor, resulting in inflammation. In this study, we explore the targeting of ß-arrestin signalling in MFS mice by administering TRV027. Furthermore, because high doses of the ARB losartan, which has been proven beneficial in MFS, cannot be achieved in humans, we investigate a potential additive effect by combining lower concentrations of losartan (25 mg/kg/day and 5 mg/kg/day) with barbadin, a ß-arrestin blocker, and DMX20, a C-C chemokine receptor type 2 (CCR2) blocker. A high dose of losartan (50 mg/kg/day) slowed down aneurysm progression compared to untreated MFS mice (1.73 ± 0.12 vs. 1.96 ± 0.08 mm, p = 0.0033). TRV027, the combination of barbadin with losartan (25 mg/kg/day), and DMX-200 (90 mg/kg/day) with a low dose of losartan (5 mg/kg/day) did not show a significant beneficial effect. Our results confirm that while losartan effectively halts aneurysm formation in Fbn1C1041G/+ MFS mice, neither TRV027 alone nor any of the other compounds combined with lower doses of losartan demonstrate a notable impact on aneurysm advancement. It appears that complete blockade of AT1R function, achieved by administrating a high dosage of losartan, may be necessary for inhibiting aneurysm progression in MFS.

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.

Cannula Placement for Cerebral Protection Without Circulatory Arrest in Patients Undergoing Hemiarch Aortic Aneurysm Repair.

BACKGROUND: Aortic aneurysms involving the proximal aortic arch, which require hemiarch-type repair, typically require circulatory arrest with antegrade cerebral perfusion. Left carotid antegrade cerebral perfusion (LCP) via distal arch cannulation without circulatory arrest was used in this study's patient population. The goal was to assess the operative efficiency and clinical outcomes of using a distal arch cannulation technique that would not require any hypothermic circulatory arrest (HCA) time compared with more traditional brachiocephalic artery cannulation with right-sided unilateral antegrade cerebral perfusion (RCP) and HCA. METHODS: A single-center retrospective review of patients with replacement of the distal ascending aorta involving the proximal arch was performed. Patients with an intramural hematoma or dissection were excluded. Between January 2015 and December 2019, 68 adult patients had undergone a hemiarch repair because of aneurysmal disease. Analysis of baseline demographics, operative data, and clinical outcomes was performed. RESULTS: Comparing the 68 patients: 21 patients were treated with RCP (via brachiocephalic artery graft with HCA), and 47 patients were treated with LCP (via distal aortic arch cannulation with cross-clamp between the brachiocephalic and left common carotid arteries without HCA). Baseline characteristics and outcomes were evaluated for both groups. The LCP group was younger (LCP median [IQR] age, 60 [53-65] years vs RCP median [IQR] age, 67 [59-71] years]. Sex, race, body mass index, comorbidities, and ejection fraction were similar between the groups. Cardiopulmonary bypass time (LCP, 123 minutes vs RCP, 149 minutes) and unilateral cerebral perfusion time (LCP, 17 minutes vs RCP, 22 minutes) were longer in the RCP group. Bleeding, prolonged ventilatory support, kidney failure, and length of stay were similar. In-hospital mortality was 2% in the LCP group vs 0% in the RCP group. Stroke occurred in 2 patients (4.2%) in the LCP group and in 0% of the RCP group. Mortality at 6 months in the LCP and RCP groups was 3% and 10%, respectively. CONCLUSION: Distal arch cannulation with LCP without HCA is a reasonable and safe alternative strategy for patients requiring hemiarch replacement for aneurysmal disease. This technique may provide additional benefits by avoiding circulatory arrest in these complex cases.

Surgery for Ascending Aortic Aneurysm and Aortic Valve Insufficiency in Conditions of Active Proceeding Syphilitic Aortitis and Valvulitis.

A syphilitic aortitis is a late cardiovascular lesion of tertiary syphilis that has become exceptionally rare in the antibiotic era but not eradicated completely. Syphilitic aortitis of ascending aorta complicates in ascending aortic aneurysm formation and aortic valve regurgitation, both requiring surgical treatment. After surgery, lifelong surveillance of the remainder of the aorta is recommended because of a priori supposed high incidence of delayed involvement of noninvolved aortic segments. A 3-year follow-up result of surgery of syphilitic ascending aortic aneurysm with aortic valve regurgitation in condition of active ongoing syphilitic aortitis and valvulitis is described with addressing the dimensions of remaining aortic segments. This case demonstrates that the dilatation of the remainder of the aorta does not occur during 3 years, at least when anti-syphilitic course of antibiotic is used just after operation without additional treatment during the follow-up period. A few reports on surgical treatment of syphilitic aneurysms of the ascending aorta are discussed.

Intra-stent aortic wall aneurysm formation after Be-graft covered stent implant.

Aortic wall injuries may occur after interventional treatment of aortic coarctation (CoA), especially after balloon angioplasty. We reported on a patient who presented with an intra-stent aneurysm formation after direct stenting of a native near atretic aortic CoA by using a BeGraft Aortic stent. This evidence supports the need to maintain a strict follow-up protocol. A computed tomography scan is mandatory, after covered stent implantation as well, especially in high-risk cases and even in the absence of any immediate apparent complication.

Risk factor analysis for aortic dissection after aortic valve replacement in patients with tricuspid aortic valve.

OBJECTIVE: Aortic dilatation concurrent with aortic valve disease is a common condition. However, the incidence of aortic dissection after aortic valve replacement for tricuspid aortic valve has not been fully investigated. Therefore, we performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. METHODS: We retrospectively reviewed 599 patients who underwent aortic valve replacement at our hospital between January 2000 and December 2020. We performed a risk factor analysis for the incidence of aortic dissection after aortic valve replacement in patients with tricuspid aortic valve. RESULTS: Seven patients developed late aortic dissections during the follow-up period. All patients with aortic dissection underwent aortic valve replacement for aortic regurgitation. Multivariable analysis revealed that aortic regurgitation was an independent predictor of aortic dissection (p < 0.0001). The mean ascending aortic diameter at aortic valve replacement for aortic regurgitation was significantly greater in patients with aortic dissection than in those without aortic dissection (46 [43.5-46] mm vs. 39 [36-42] mm, p < 0.001). The predictive cutoff value of ascending aortic diameter was indicated using receiver operating characteristic curve analysis; 46.0 mm (area under the curve: 0.8987). Freedom rates from aortic dissection in patients with aortic regurgitation and an ascending aortic diameter ≥ 46 mm were significantly lower than those in patients with an ascending aortic diameter < 46 mm (66.7% vs. 100% at 5 years, p < 0.0001). CONCLUSION: Aortic regurgitation combined with ascending aortic dilatation at aortic valve replacement could be a significant risk factor for late aortic dissection.

Shared decision-making and specific informed consent in patients with aortic aneurysms.

OBJECTIVE: To analyze the refusal rate of elective aortic aneurysm surgery in asymptomatic patients after the presentation of a detailed informed consent form followed by a meeting where patient and their families can analyze each item. METHODS: We conducted a retrospective analysis of 49 patients who had aneurysms and were offered surgical treatment between June 2017 and February 2019. The patients were divided into two groups: the Rejected Surgery Group, which was composed of patients who refused the proposed surgical treatment, and the Accepted Surgery Group, comprising patients who accepted the proposed surgeries and subsequently underwent them. RESULTS: Of the 49 patients, 13 (26.5%) refused surgery after reading the informed consent and attending the comprehensive meeting. We observed that patients who refused surgery had statistically smaller aneurysms than those who accepted surgery (9% versus 26%). These smaller aneurysms were above the indication size, according to the literature. CONCLUSION: One-quarter of patients who were indicated for elective surgical repair of aortic aneurysms rejected surgery after shared decision-making, which involved presenting patients with an informed consent form followed by a clarification meeting for them and their families to analyze each item. The only factor that significantly influenced a rejection of the procedure was the size of the aneurysm; patients who rejected surgery had smaller aneurysms than those who accepted surgery. Up to 26% of patients with aortic aneurysms refused surgical repair. The proposed technique, whether open or endovascular, did not influence patients' decisions. Patients with smaller aneurysms were more likely to refuse aortic aneurysm treatment.

Aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet's disease: a case report and literature review.

Few case reports have mentioned the aortic sinus aneurysm invading ventricular septum and dissection caused by Behcet's disease. Here, we reported a 36-year-old male patient with an aortic sinus aneurysm invading the ventricular septum and dissection caused by Behcet's disease, who manifested as recurrent chest tightness and shortness of breath. Cardiac ultrasound showed the rupture of the right aortic sinus and the formation of ventricular septal dissection. Ascending aortic valve prosthesis replacement, mitral valvuloplasty with ring implantation and tricuspid valvuloplasty were performed. Postoperatively, he was treated with hormones, hydroxychloroquine sulfate, mycophenolate mofetil tablets, thalidomide and warfarin, and his symptoms were relieved. This is a rare case easily being misdiagnosed and missed, early diagnosis and in-time treatment are crucial to avoid surgical complications. The diagnostic and therapeutic approaches of this patient were reported and related literature was reviewed in this case report.

Iatrogenic Acute Ascending Aortic Dissection During Combined Heart/Liver Transplant for Amyloidosis.

We report a case of iatrogenic acute type A aortic dissection (ATAAD) during a combined heart-liver transplant in a patient with amyloid-associated cardiac and hepatic failure. The patient developed ATAAD of the recipient's aorta during the heart transplantation. Because there was no sign of malperfusion or proximal extension into the donor aorta, we proceeded with the liver transplantation and continued medical management for ATAAD. The patient was discharged uneventfully 30 days after the transplant, and computed tomography coronary angiogram after 4 months showed stable dissection. During a heart transplant, ATAAD of the native aorta without malperfusion syndrome can be managed conservatively with close progress monitoring.

Combined ascending aortobiiliac bypass and endovascular obliteration in the Bentall procedure for dual aortic aneurysms.

Patients with Marfan syndrome who present with a dual aortic aneurysm are not uncommon in clinical practice; however, the management of these patients is a significant challenge. We present a unique case of aortic root aneurysm and challenging infrarenal abdominal aortic aneurysm (AAA) with a short and angulated neck. We performed simultaneous repair using the Bentall procedure and ascending aortobiiliac bypass. Endovascular obliteration of the AAA neck and bilateral common iliac arteries was also performed. The perioperative process was uneventful. Normal functioning of the mechanical valve and complete thrombosis of the AAA sac were confirmed on follow-up computed tomography and echocardiography. This report suggests that combined ascending aortobiiliac bypass and endovascular obliteration with the Bentall procedure for dual aortic aneurysm is a useful surgical strategy for patients with Marfan syndrome. Life-long follow-up and medication ought to be mandatory to prevent incomplete exclusion and bypass occlusion.

Risk Factors Associated with Spinal Cord Ischemia During Aortic Aneurysm Repair.

BACKGROUND: The risk of spinal cord ischemia (SCI) with aortic aneurysm repair can cause significant neurological morbidity. Prevention of SCI is critical. We sought to identify risk factors that predispose to SCI that may guide strategies to mitigate the occurrence of SCI during and following these procedures. METHODS: This study includes all adults who underwent atraumatic, unruptured, thoracic, and suprarenal aortic aneurysm repairs (endovascular or open) at our institution over 11 years (2010-2020). Our database included patient demographics, aneurysm anatomic features, and operative characteristics and an extreme gradient boost (XGB) machine method was used to develop a predictive model for SCI. The model was trained on an 80% randomly stratified cohort of the data and tested on the remaining 20% testing cohort. Shapley values were used to determine the most important predictive factors of SCI and decision trees were used to identify risk factor threshold values and highest risk factor combinations. RESULTS: Information was collected for 174 adult patients undergoing thoracic and suprarenal aortic repair from 2010 to 2020. Fifty eight percent of the patients were male. Ninety seven (55.7%) patients had open aortic repair and 87 (44.3%) had endovascular repair. Twenty seven (15%) of all patients had major complications and were considered to have SCI. The XGB model converged over the training cohort with a testing cohort accuracy of 0.841 [Sensitivity = 75%, Specificity = 68%] and area under the curve of receiver operating characteristic of 0.774. The XGB model identified older age (> 65 years), history of neurologic disease, hyperlipidemia, diabetes, coronary artery disease, heart failure, poor renal function, < 6 months since last aortic repair, chronic anticoagulant use, preoperational anemia (Hemoglobin < 9), thrombocytopenia (platelet < 90,000), coagulopathy (prothrombin time > 15s and activated partial thromboplastin time > 40s), hypotension (mean arterial pressure < 70 mm Hg), longer operations (> 100 min), aneurysms longer than 5 cm, and anatomic location of aneurysm caudal to T-11 as risk factors for SCI in all types of aortic repair. Diabetic and heart failure patients undergoing longer operations (> 100 min) with thrombocytopenia or aneurysms longer than 5 cm were at the highest risk. CONCLUSIONS: The XGB model accurately identified risk factors of SCI with aortic aneurysm repair that may guide patient selection, timing of surgery, and strategies to minimize the risk of SCI.

Smoking Cessation and Mortality from Aortic Dissection and Aneurysm: Findings from the Japan Collaborative Cohort (JACC) Study.

AIMS: Active cigarette smoking was intensively reported to increase the risk of aortic mortality while research on the association between smoking cessation and aortic mortality remains scarce. This study aimed to reconfirm the associations of exposure to cigarettes and smoking cessation associated with aortic mortality in a large Japanese population. METHODS: In the Japan Collaborative Cohort (JACC) Study, 91,141 residents (57±10 years; men, 43%) who were free of stroke, coronary heart disease, and cancer were followed up from 1989-90 until 2009 during which 110 deaths from aortic dissection and 112 deaths from aneurysm were identified. Cox proportional hazard model was used to estimate multivariable hazard ratios (95%CI) for total and specific aortic mortality. RESULTS: Compared to never smoking, HRs for total aortic mortality were 2.39 (1.40-4.08) for ＜20, 3.57 (2.19-5.83) for 20-39, and 3.92 (2.37-6.48) for ≥ 40 pack-years exposure. Compared to current smoking, HRs for total aortic mortality were 0.42 (0.18-0.97) for 10-15 years, 0.27 (0.11-0.66) for ＞15 years of cessation, and 0.24 (0.13-0.44) for never smoking. Similar inverse dose-response pattern was observed between smoking cessation duration and risk of mortality from aortic aneurysm (p for trend=0.001), but the association with aortic dissection mortality did not reach statistical significance. CONCLUSIONS: Cigarette smoking was associated with an increased risk of aortic mortality while smoking cessation was so with a reduced risk among the Japanese population.