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PloS One 2024Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow...
BACKGROUND
Bicuspid aortic valves (BAV) are frequently associated with ascending aortic aneurysms. The etiology is incompletely understood, but genetic factors, in addition to flow perturbations, are likely involved. Since loss of contractility and elaboration of extracellular matrix in the vessel wall are features of BAV-associated aortopathy, phenotypic modulation of smooth muscle cells (SMCs) may play a role.
METHODS
Ascending aortic tissue was collected intra-operatively from 25 individuals with normal (i.e., tricuspid) aortic valves (TAV) and from 25 individuals with BAVs. For both TAV and BAV, 10 patients had non-dilated (ND) and 15 patients had dilated (D) aortas. SMCs were isolated and cultured from a subset of patients from each group. Aortic tissue and SMCs were fluorescently immunolabeled for SMC phenotypic markers (i.e., alpha-smooth muscle actin (ASMA, contractile), vimentin (synthetic) and p16INK4a and p21Cip1 (senescence). SMCs were also analyzed for replicative senescence in culture.
RESULTS
In normal-sized and dilated BAV aortas, SMCs switched from the contractile state to either synthetic or senescent phenotypes, as observed by loss of ASMA (ND: P = 0.001, D: P = 0.002) and associated increases in vimentin (ND: P = 0.03, D: P = 0.004) or p16/p21 (ND: P = 0.03, D: P<0.0001) compared to TAV. Dilatation of the aorta exacerbated SMC phenotypic switching in both BAV and TAV aortas (all P<0.05). In SMCs cultured from normal and dilated aortas, those isolated from BAV reached replicative senescence faster than those from TAV aortas (all P = 0.02). Furthermore, there was a stark inverse correlation between ASMA and cell passage number in BAV SMCs (ND: P = 0.0006, D: P = 0.01), but not in TAV SMCs (ND: P = 0.93, D: P = 0.20).
CONCLUSIONS
The findings of this study provide direct evidence from cell culture studies implying that SMCs switch from the contractile state to either synthetic or senescent phenotypes in the non-dilated BAV aorta. In cultured SMCs from both non-dilated and dilated aortas, we found that this process may precede dilatation and accompany aneurysm development in BAV. Our findings suggest that therapeutically targeting SMC phenotypic modulation in BAV patients may be a viable option to prevent or delay ascending aortic aneurysm formation.
Topics: Humans; Aortic Valve; Bicuspid Aortic Valve Disease; Myocytes, Smooth Muscle; Heart Valve Diseases; Aorta; Male; Middle Aged; Phenotype; Female; Dilatation, Pathologic; Adult; Cellular Senescence; Cells, Cultured; Aged; Actins; Aortic Aneurysm; Vimentin
PubMed: 38954721
DOI: 10.1371/journal.pone.0306515 -
Journal of Cardiothoracic Surgery Jun 2024The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive...
BACKGROUND
The outcomes of Thoracic Endovascular Aortic Repair (TEVAR) vary depending on thoracic aortic pathologies, comorbidities. This study presents our comprehensive endovascular experience, focusing on exploring the outcome in long term follow-up.
METHODS
From 2006 to 2018, we conducted TEVAR on 97 patients presenting with various aortic pathologies. This retrospective cohort study was designed primarily to assess graft durability and secondarily to evaluate mortality causes, complications, reinterventions, and the impact of comorbidities on survival using Kaplan-Meier and Cox regression analyses.
RESULTS
The most common indication was thoracic aortic aneurysm (n = 52). Ten patients had aortic arch variations and anomalies, and the bovine arch was observed in eight patients. Endoleaks were the main complications encountered, and 10 of 15 endoleaks were type I endoleaks. There were 18 reinterventions; the most of which was TEVAR (n = 5). The overall mortality was 20 patients, with TEVAR-related causes accounting for 12 of these deaths, including intracranial bleeding in three patients. Multivariant Cox regression revealed chronic renal diseases (OR = 11.73; 95% CI: 2.04-67.2; p = 0.006), previous cardiac operation (OR = 14.26; 95% CI: 1.59-127.36; p = 0.01), and chronic obstructive pulmonary diseases (OR = 7.82; 95% CI: 1.43-42.78; p = 0.001) to be independent risk factors for 10-year survival. There was no significant difference in the survival curves of the various aortic pathologies. In the follow-up period, two non-symptomatic intragraft thromboses and one graft infection were found.
CONCLUSION
Comorbidities can increase the risk of TEVAR-related mortality without significantly impacting endoleak rates. TEVAR is effective for severe aortic pathologies, though long-term graft durability may be compromised by its thrombosis and infection.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Endovascular Procedures; Aorta, Thoracic; Aged; Blood Vessel Prosthesis Implantation; Treatment Outcome; Aortic Diseases; Postoperative Complications; Adult; Aortic Aneurysm, Thoracic; Follow-Up Studies; Time Factors; Endovascular Aneurysm Repair
PubMed: 38951901
DOI: 10.1186/s13019-024-02886-6 -
Thrombosis and Haemostasis Jul 2024Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture...
OBJECTIVE
Hereditary aortic diseases (hADs) increase the risk of aortic dissections and ruptures. Recently, we have established an objective approach to measure the rupture force of the murine aorta, thereby explaining the outcomes of clinical studies and assessing the added value of approved drugs in vascular Ehlers-Danlos syndrome (vEDS). Here, we applied our approach to six additional mouse hAD models.
MATERIAL AND METHODS
We used two mouse models ( and ) of Marfan syndrome (MFS) as well as one smooth-muscle-cell-specific knockout (SMKO) of and three CRISPR/Cas9-engineered knock-in models (, , and ). One of the two MFS models was subjected to 4-week-long losartan treatment. Per mouse, three rings of the thoracic aorta were prepared, mounted on a tissue puller, and uniaxially stretched until rupture.
RESULTS
The aortic rupture force of the SMKO and both MFS models was significantly lower compared with wild-type mice but in both MFS models higher than in mice modeling vEDS. In contrast, the , , and knock-in models presented no impaired aortic integrity. As expected, losartan treatment reduced aneurysm formation but surprisingly had no impact on the aortic rupture force of our MFS mice.
CONCLUSION
Our read-out system can characterize the aortic biomechanical integrity of mice modeling not only vEDS but also related hADs, allowing the aortic-rupture-force-focused comparison of mouse models. Furthermore, aneurysm progression alone may not be a sufficient read-out for aortic rupture, as antihypertensive drugs reducing aortic dilatation might not strengthen the weakened aortic wall. Our results may enable identification of improved medical therapies of hADs.
PubMed: 38950604
DOI: 10.1055/s-0044-1787957 -
World Journal of Experimental Medicine Jun 2024Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for... (Review)
Review
Aortic aneurysm (AA) refers to the persistent dilatation of the aorta, exceeding three centimeters. Investigating the pathophysiology of this condition is important for its prevention and management, given its responsibility for more than 25000 deaths in the United States. AAs are classified based on their location or morphology. various pathophysiologic pathways including inflammation, the immune system and atherosclerosis have been implicated in its development. Inflammatory markers such as transforming growth factor β, interleukin-1β, tumor necrosis factor-α, matrix metalloproteinase-2 and many more may contribute to this phenomenon. Several genetic disorders such as Marfan syndrome, Ehler-Danlos syndrome and Loeys-Dietz syndrome have also been associated with this disease. Recent years has seen the investigation of novel management of AA, exploring the implication of different immune suppressors, the role of radiation in shrinkage and prevention, as well as minimally invasive and newly hypothesized surgical methods. In this narrative review, we aim to present the new contributing factors involved in pathophysiology of AA. We also highlighted the novel management methods that have demonstrated promising benefits in clinical outcomes of the AA.
PubMed: 38948412
DOI: 10.5493/wjem.v14.i2.91408 -
IDCases 2024Infections associated with healthcare manipulations, particularly bloodstream infections stemming from catheters and medical devices, significantly heighten the...
Infections associated with healthcare manipulations, particularly bloodstream infections stemming from catheters and medical devices, significantly heighten the probability of vertebral osteomyelitis. The diagnosis of infective endocarditis (IE) frequently overlaps with vertebral osteomyelitis (VO). In cases where individuals are suspected of having hematogenous vertebral osteomyelitis and have an intravascular catheter or device, it is recommended to undertake blood culture collection. We present a case of a 39-year-old male with a history of interventional AVM embolization and cerebral angiography, experiencing recurrent vertebral osteomyelitis. No definitive source of infection had been found, and transthoracic echocardiography (TTE) yielded negative results for IE. In Trans Esophageal Echocardiography (TEE), a retained micro-catheter extending from the aortic arch to the inguinal artery was discovered. Although we cannot definitively attribute the source of the osteomyelitis to the retained micro-catheter, no episodes of infection have been reported ever since. This case underscores the need to enhance our approaches and guidelines related to operating protocols in the surgical setting. Improving these guidelines can prevent similar occurrences in the future, emphasizing the importance of continuous improvement in healthcare practices.
PubMed: 38947558
DOI: 10.1016/j.idcr.2024.e02005 -
BMC Cardiovascular Disorders Jun 2024The purpose of this study was to review echocardiography-based diagnosis of persistent fifth aortic arch (PFAA) in children.
BACKGROUND
The purpose of this study was to review echocardiography-based diagnosis of persistent fifth aortic arch (PFAA) in children.
METHODS
From January 2015 to December 2022, we retrospectively analyzed the echocardiographic findings and the relevant clinical data during follow-up of patients with PFAA who were treated in the Third Affiliated Hospital of Zhengzhou University. The diagnosis was confirmed by computed tomography angiography or surgery.
RESULTS
Seven PFAA cases included two Weinberg type A and five Weinberg type B. The anatomical details of PFAA were assessed using a combination of the long-axis view of the left ventricular outflow tract (from the left high parasternal window) and the long-axis view of the aortic arch (from the suprasternal window). In Weinberg type A, the distal fifth and fourth aortic arches were connected to the descending aorta, which was associated with aortic coarctation. In Weinberg type B, the upper arch of the fourth aorta was interrupted, and only the lower arch of the fifth aorta was connected to the descending aorta. Surgical repair of PFAA was indicated in five patients with blood flow disruption, among which four had good postoperative results and one refused surgery. Two patients with unobstructed PFAA blood flow required follow-up rather than surgery.
CONCLUSIONS
It is feasible to diagnose PFAA by echocardiography. Combined application of the high parasternal left ventricular outflow tract view and the suprasternal aortic arch view can improve timely detection of different types of PFAA in children.
Topics: Humans; Aorta, Thoracic; Retrospective Studies; Male; Female; Computed Tomography Angiography; Infant; Predictive Value of Tests; Child, Preschool; Aortography; Child; China; Aortic Coarctation; Treatment Outcome; Age Factors; Reproducibility of Results; Echocardiography
PubMed: 38943106
DOI: 10.1186/s12872-024-03999-5 -
Interdisciplinary Cardiovascular and... Jun 2024Less invasive surgery has emerged as an option for aortic pathologies. The current study compared our experience on early postoperative results of patients with aortic...
OBJECTIVES
Less invasive surgery has emerged as an option for aortic pathologies. The current study compared our experience on early postoperative results of patients with aortic surgery between partial upper sternotomy (PUS) and full sternotomy (FS).
METHODS
We performed a retrospective analysis of the data of patients undergoing aortic root surgery with concomitant ascending aorta and hemiarch replacement. Exclusion criteria were type A aortic dissection and other concomitant major cardiac surgery. After propensity-score matching, we compared the perioperative outcomes of patients undergoing surgery with PUS vs FS.
RESULTS
161 patients operated on between January 2013 and September 2022 met the inclusion criteria (PUS: n = 22, FS: n = 139). Propensity score matching yielded 22 pairs with a balanced distribution of propensity scores and covariates between the compared groups. There was no evidence that PUS affects cardiopulmonary bypass [108(67-119) vs 113(87-148) min, p = 0.154; PUS vs FS] and circulatory arrest duration [9(7-10) vs 9(8-13) min, p = 0.264; PUS vs FS]. There was a reduced cross-clamp duration in the PUS group [88(58-96) vs 92(71-122) min, p = 0.032]. Cumulative sum charts (CUSUM) have shown consistently low cross-clamp and circulatory arrest duration for two experienced surgeons who performed 20 of the procedures in the PUS group (10 each). Perioperative mortality and morbidity were low, with no in-hospital mortality in the PUS group [0 vs 1(4.5%), p > 0.999] and absence of strokes in both groups.
CONCLUSIONS
In summary, our initial experience suggests that less invasive aortic root, ascending aorta, and hemiarch replacement via partial upper sternotomy could be performed in our patient cohort as safely as via full sternotomy. Advantages for the patient are reduced surgical trauma, improved cosmetic results, and-presumably-less pain.
PubMed: 38941507
DOI: 10.1093/icvts/ivae120 -
Sheng Li Xue Bao : [Acta Physiologica... Jun 2024The purpose of the present study was to investigate the modeling time of type 2 diabetes mellitus (T2DM) mouse model induced by high fat diet (HFD) alone and the effects...
The purpose of the present study was to investigate the modeling time of type 2 diabetes mellitus (T2DM) mouse model induced by high fat diet (HFD) alone and the effects of HFD on the pathology and function of organs related to glucose and lipid metabolism. C57BL/6 mice were fed with normal diet (NC group) or HFD (HFD group). The time of successful T2DM modeling was evaluated by measuring body weight, fasting blood glucose and glucose tolerance at time points of 0, 4, 8, 12, 16 and 20 weeks. The functional and pathological changes of glucose and lipid metabolism related organs were evaluated by detecting insulin tolerance, plasma lipid levels, vascular function, as well as HE staining of pancreas and liver. The results showed that compared with the NC group, the HFD group had significantly increased body weight after 8 weeks of HFD. After 16 weeks of HFD, the HFD group exhibited impaired fasting glucose tolerance. After 20 weeks of HFD, the HFD group mice reached diabetic state, showing impaired glucose tolerance and insulin resistance, islet volume reduction and vacuolar degeneration; Large number of lipid droplets appeared in liver cells, and the level of AMPK phosphorylation in liver tissue was significantly increased in the HFD groups, compared with the NC group; There was endothelial dependent diastolic dysfunction in the thoracic aorta of the HFD group; Compared with the NC group, the HFD group mice showed a significant increase in urinary protein levels. These results suggest that T2DM mouse model can be successfully established by HFD induction alone for 20 weeks. The model is characterized by insulin resistance, fatty liver, hyperlipidemia, vascular dysfunction, renal dysfunction and pathological changes of islet and liver cells, which are similar to those of T2DM patients. Therefore it can be used as an ideal animal model for T2DM research.
Topics: Animals; Diabetes Mellitus, Type 2; Mice; Diet, High-Fat; Mice, Inbred C57BL; Male; Disease Models, Animal; Insulin Resistance; Lipid Metabolism; Diabetes Mellitus, Experimental; Liver
PubMed: 38939933
DOI: No ID Found -
JACC. Advances Feb 2024The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available...
BACKGROUND
The number of patients with an arterial switch operation (ASO) for transposition of the great arteries (TGA) is steadily growing; limited information is available regarding the clinical course in the current era.
OBJECTIVES
The purpose was to describe clinical outcome late after ASO in a national cohort, including survival, rates of (re-)interventions, and clinical events.
METHODS
A total of 1,061 TGA-ASO patients (median age 10.7 years [IQR: 2.0-18.2 years]) from a nationwide prospective registry with a median follow-up of 8.0 years (IQR: 5.4-8.8 years) were included. Using an analysis with age as the primary time scale, cumulative incidence of survival, (re)interventions, and clinical events were determined.
RESULTS
At the age of 35 years, late survival was 93% (95% CI: 88%-98%). The cumulative re-intervention rate at the right ventricular outflow tract and pulmonary branches was 36% (95% CI: 31%-41%). Other cumulative re-intervention rates at 35 years were on the left ventricular outflow tract (neo-aortic root and valve) 16% (95% CI: 10%-22%), aortic arch 9% (95% CI: 5%-13%), and coronary arteries 3% (95% CI: 1%-6%). Furthermore, 11% (95% CI: 6%-16%) of the patients required electrophysiological interventions. Clinical events, including heart failure, endocarditis, and myocardial infarction occurred in 8% (95% CI: 5%-11%). Independent risk factors for any (re-)intervention were TGA morphological subtype (Taussig-Bing double outlet right ventricle [HR: 4.9, 95% CI: 2.9-8.1]) and previous pulmonary artery banding (HR: 1.6, 95% CI: 1.0-2.2).
CONCLUSIONS
TGA-ASO patients have an excellent survival. However, their clinical course is characterized by an ongoing need for (re-)interventions, especially on the right ventricular outflow tract and the left ventricular outflow tract indicating a strict lifelong surveillance, also in adulthood.
PubMed: 38939383
DOI: 10.1016/j.jacadv.2023.100772 -
JACC. Advances Mar 2024Augmented reality (AR) guidance holds potential to improve transcatheter interventions by enabling visualization of and interaction with patient-specific 3-dimensional...
BACKGROUND
Augmented reality (AR) guidance holds potential to improve transcatheter interventions by enabling visualization of and interaction with patient-specific 3-dimensional virtual content. Positioning of cerebral embolic protection devices (CEP) during transcatheter aortic valve replacement (TAVR) increases patient exposure to radiation and iodinated contrast, and increases procedure time. AR may enhance procedural guidance and facilitate a safer intervention.
OBJECTIVES
The purpose of this study was to develop and test a novel AR guidance system with a custom user interface that displays virtual, patient-specific 3-dimensional anatomic models, and assess its intraprocedural impact during CEP placement in TAVR.
METHODS
Patients undergoing CEP during TAVR were prospectively enrolled and assigned to either AR guidance or control groups. Primary endpoints were contrast volume used prior to filter placement, times to filter placement, and fluoroscopy time. Postprocedure questionnaires were administered to assess intraprocedural physician experience with AR guidance.
RESULTS
A total of 24 patients presenting for TAVR were enrolled in the study (12 with AR guidance and 12 controls). AR guidance eliminated the need for aortic arch angiograms prior to device placement thus reducing contrast volume (0 mL vs 15 mL, < 0.0001). There was no significant difference in the time required for filter placement or fluoroscopy time. Postprocedure questionnaires indicated that AR guidance increased confidence in wiring of the aortic arch and facilitated easier device placement.
CONCLUSIONS
We developed a novel AR guidance system that eliminated the need for additional intraprocedural angiograms prior to device placement without any significant difference in time to intervention and offered a subjective improvement in performance of the intervention.
PubMed: 38938839
DOI: 10.1016/j.jacadv.2024.100839