Acute aortic dissection in the Marfan syndrome during the COVID-19 epidemic.
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ABSTRACT:
SUBMITTER: Basheer A
PROVIDER: S-EPMC8682858 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAccording to previous studies, aortic diameter alone seems to be insufficient to predict the event of aortic dissection in Marfan syndrome (MFS). Determining the optimal schedule for preventive aortic root replacement (ARR) aortic growth rate is of importance, as well as family history, however, none of them appear to be decisive. Thus, the aim of this study was to search for potential predictors of aortic dissection in MFS.MethodsA Marfan Biobank consisting of 79 MFS patients was established. Thirty-nine MFS patients who underwent ARR were assigned into three groups based on the indication for surgery (dissection, annuloaortic ectasia and prophylactic surgery). The prophylactic surgery group was excluded from the study. Transforming growth factor-? (TGF-?) serum levels were measured by ELISA, relative expression of c-Fos, matrix metalloproteinase 3 and 9 (MMP-3 and -9) were assessed by RT-PCR. Clinical parameters, including anthropometric variables - based on the original Ghent criteria were also analyzed.ResultsAmong patients with aortic dissection, TGF-? serum level was elevated (43.78 ± 6.51 vs. 31.64 ± 4.99 ng/l, p < 0.0001), MMP-3 was up-regulated (Ln2? = 1.87, p = 0.062) and striae atrophicae were more common (92% vs. 41% p = 0.027) compared to the annuloaortic ectasia group.ConclusionsWe found three easily measurable parameters (striae atrophicae, TGF-? serum level, MMP-3) that may help to predict the risk of aortic dissection in MFS. Based on these findings a new classification of MFS, that is benign or malignant is also proposed, which could be taken into consideration in determining the timing of prophylactic ARR.
| S-EPMC4021409 | biostudies-literature
Project description:Women with Marfan syndrome (MFS) are at high risk for pregnancy-associated aortic dissection. Pathogenic models that singularly invoke hemodynamic stress are difficult to reconcile with predominant postnatal occurrence of aortic tear, often occurring weeks to months after delivery. In consideration of events that peak at term, are sustained after delivery, and might synergize with previously defined signaling pathways implicated in aneurysm progression, we examined the hormone oxytocin, which initiates uterine contraction and milk letdown for the duration of lactation through phosphorylation of extracellular signal-regulated kinase (ERK). In a mouse model of MFS that shows highly penetrant postnatal aortic dissection, risk was strongly attenuated by preventing lactation or use of an oxytocin receptor antagonist. Survival correlated inversely with the extent of ERK activation in the aortic wall, and strong protection was observed upon attenuation of ERK phosphorylation using an inhibitor of ERK kinase (MEK) or the U.S. Food and Drug Administration-approved medication hydralazine, offering potential therapeutic strategies for pregnancy-associated vascular catastrophe in the setting of MFS.
| S-EPMC8285055 | biostudies-literature
Project description:BackgroundMarfan syndrome (MFS) is an inherited connective tissue disease that mainly involves Fibrillin-1 (FBN1) mutations and aortic manifestations. In this study, we investigated the correlations between the FBN1 genotype-phenotype and aortic events (aortic dissection and aortic aneurysm) in patients with Marfan syndrome.MethodsGenotype and phenotype information was evaluated in 180 patients with MFS. DNA sequencing was performed on each patient. According to the clinical manifestation, these patients were split into two groups: the aortic dissection group and the aortic aneurysm group. Aortic wall tissue was obtained from Marfan patients who underwent surgery and was used for staining.ResultsA total of 180 patients with FBN1 mutations were grouped into four categories: 90 with missense mutations, 32 with splicing mutations, 29 with frameshift mutations, and 29 with nonsense mutations. There was a significantly higher frequency of frameshift and nonsense mutations observed in aortic dissection than in aortic aneurysm (25.58% vs. 4.35%, p = .005; 25.58% vs. 8.70%, p = .033, respectively;), while missense mutations showed a higher frequency in aortic aneurysm than in aortic dissection (69.57% vs. 32.56%, respectively; p < .001) and a higher rate of lens dislocation (34.78% vs. 13.95%, respectively; p = .008). Pathological staining showed that elastic fibers were sparser in patients with a frameshift and nonsense mutations, and the smooth muscle cells were sparser and more disorganized than those observed in patients with missense mutations.ConclusionThis study showed that FBN1 gene frameshift and nonsense mutations are more common in patients with aortic dissection and may have meaningful guidance for the treatment of Marfan syndrome patients.
| S-EPMC6978253 | biostudies-literature
Project description:Marfan syndrome (MFS) is an autosomal dominant connective disease etiologically related with FBN-1 gene mutation. The altered microfibril protein structure result in characteristic cardiovascular abnormalities including aortic root dilatation, aortic root aneurysms, and aortic dissections. Aortic root aneurysms and subsequent dissection are the major causes of reduced life expectancy in MFS patients. Prophylactic aortic root replacement has improved the survival of patients with MFS. Elective root replacement carries very low mortality and morbidity. Emergency root replacement for dissection is accompanied with higher early mortality and late deaths/interventions. Both the techniques of aortic root replacement, total root replacement (TRR) with a prosthetic valved conduit, and valve-sparing root replacement (VSRR) yield excellent early and late results. Considering the low risk of prosthetic valve-related events, the improved long-term survival, and event-free survival, TRR continues to be a very effective surgical option. VSSR also seems to be a good option for the first 10 to 15 years following surgery in MFS patients. The choice of procedure depends upon available expertise, patients' choice, feasibility of anticoagulation, possibility of pregnancy, and lifestyle of the patient. Aortic root morphology and state of valve cusps also affect the decision making. In recent times, personalized external aortic root support (PEARS) with a macroporous mesh sleeve has also emerged as a promising alternative to aortic root replacement. All these patients need close monitoring for whole life after surgical intervention.
| S-EPMC7525511 | biostudies-literature
Project description:Aortic dissection (AD) is mainly caused by hypertension and Marfan syndrome. However, it is unclear whether the cellular components and functions are different between the two causes. A total of 11 aortic samples were collected for single-cell RNA analysis and 20 clusters were disclosed, including VSMCs, fibroblasts, endothelial cells, T cells, B cells, monocytes, macrophages, mast cells, and neutrophils components. There were differences in cell subclusters and function between hypertension and Marfan patients. The cells also had different differentiations. Cellchat identified cell ligand-receptor interactions that were associated with hypertension and Marfan-induced AD involving SMC, fibroblast, mo-macrophages, and T-cell subsets. This study revealed the heterogeneity of cellular components and gene changes in hypertension and Marfan-induced AD. Through functional analysis and the changes in intercellular communication, the possible mechanisms of different causes of AD were explained from a new perspective, so we can better understand the occurrence and development of diseases.
| S-EPMC9253298 | biostudies-literature
Project description:We report dynamic temporal and spatial smooth muscle cell phenotype modulation using aortic single cell RNA sequencing in a murine model of Marfan syndrome (Fbn1C1041G/+) and littermate controls. Aortic root/ascending aortic tissue samples from both genotypes were studied at 4 and 24 weeks of age. The non-aneurysmal descending thoracic aorta was also studied at 24 weeks. Finally human aortic tissue from a Marfan syndrome patient undergoing aneurysm repair surgery was studied.
2020-06-30 | GSE153534 | GEO
Project description:Introduction. Marfan syndrome (MFS) is a rare connective tissue disorder attributed to a defect in the fibrillin-1 gene. Aortic aneurysms and dissection are common causes of morbidity and mortality in Marfan syndrome. Case Report. A 43-year-old female with a history of MFS and a 4.0?cm dilated ascending aorta presented to her cardiologist reporting that since a C-section two years prior, the left side of her abdomen painlessly protruded when standing. An outpatient CT scan of the abdomen/pelvis noted a 5.5?cm abdominal aortic dissection, and she was directed to the hospital. Repeat CT scan of the abdomen/pelvis revealed a 5.6?cm dissecting aneurysm of the infrarenal abdominal aorta. The patient was admitted to the ICU and started on a nitroglycerin drip to maintain systolic blood pressure less than 110?mmHg. The patient underwent repair of her abdominal aortic dissection via a retroperitoneal approach, and she tolerated the procedure well. She was started on metoprolol tartrate 12.5?mg BID and aspirin 81?mg postoperatively. She was safely discharged with follow-up care. Conclusion. This case stresses the importance of having a low threshold to obtain imaging in a MFS patient with protruding abdomen, even though the patient may not have pain and be hemodynamically stable.
| S-EPMC7060880 | biostudies-literature
Project description:Background: Sex-related differences as well as the adverse effect of pregnancy on aortic disease outcome are well-established phenomena in humans with Marfan syndrome (MFS). The underlying mechanisms of these observations are largely unknown.Objectives: In an initial (pilot) step we aimed to confirm the differences between male and female MFS patients as well as between females with and without previous pregnancy. We then sought to evaluate whether these findings are recapitulated in a pre-clinical model and performed in-depth cardiovascular phenotyping of mutant male and both nulliparous and multiparous female Marfan mice. The effect of 17?-estradiol on fibrillin-1 protein synthesis was compared in vitro using human aortic smooth muscle cells and fibroblasts.Results: Our small retrospective study of aortic dimensions in a cohort of 10 men and 20 women with MFS (10 pregnant and 10 non-pregnant) confirmed that aortic root growth was significantly increased in the pregnant group compared to the non-pregnant group (0.64mm/year vs. 0.12mm/year, p = 0.018). Male MFS patients had significantly larger aortic root diameters compared to the non-pregnant and pregnant females at baseline and follow-up (p = 0.002 and p = 0.007, respectively), but no significant increase in aortic root growth was observed compared to the females after follow-up (p = 0.559 and p = 0.352). In the GT-8/+ MFS mouse model, multiparous female Marfan mice showed increased aortic diameters when compared to nulliparous females. Aortic dilatation in multiparous females was comparable to Marfan male mice. Moreover, increased aortic diameters were associated with more severe fragmentation of the elastic lamellae. In addition, 17?-estradiol was found to promote fibrillin-1 production by human aortic smooth muscle cells.Conclusions: Pregnancy-related changes influence aortic disease severity in otherwise protected female MFS mice and patients. There may be a role for estrogen in the female sex protective effect.
| S-EPMC5510874 | biostudies-literature
Project description:Coronavirus disease 2019 (COVID-19) has substantially disrupted many processes of care related to emergency cardiac conditions, while there has been no clinical guidance regarding the management of type A aortic dissection. A retrospective multicenter study involving 52 consecutive patients (mean age 52.3, 28.9% women) with type A aortic dissection during COVID-19 pandemic was conducted at tertiary aortic centers in Michigan, Wuhan and Changsha (China). Twenty-four (46.2%) were considered clinically suspicious for COVID-19 based on radiographic lung lesions (70.8%) followed by dyspnea (25.0%), cough (12.5%), and fever (12.5%). Overall, 47 (90.4%) underwent an operation and 5 (9.6%) managed nonoperatively. All suspected patients underwent a reverse-transcriptase-polymerase-chain-reaction at arrival, whereas 82.1% in the nonsuspected (P = 0.054). Among the 24 patients either nonoperatively managed or whose operation was delayed for >24 hours, only 1 (4.2%) died. A total of 3 (6.4%) operated patients had a positive reverse-transcriptase-polymerase-chain-reaction at various timings, including 1 nonsuspected patient preoperatively and 2 with very recent COVID-19 infection. The first patient died of respiratory failure despite uneventful surgical repair and maximal medical management. The postoperative course of both patients with recent COVID-19 was characterized by severe coagulopathy requiring massive transfusions and prolonged ICU stay. However, both survived to hospital discharge. In light of the possible dismal outcomes associated with dual diagnoses of type A aortic dissection/COVID-19 and the higher-than-expected number of asymptomatic carriers, all type A dissection patients should be immediately tested for COVID-19. Surgical interventions in patients recovered from recent COVID-19 may be safe.
| S-EPMC7648657 | biostudies-literature
Project description:ObjectiveThe coronavirus disease 2019 (COVID-19) pandemic has posed challenges to health care services across the world. There has been a significant restructuring of health care resources to protect services for patients with COVID-19-related illness and to maintain emergency and urgent medical and surgical activity. This study assessed access to emergency treatment, logistical challenges, and outcomes of patients with acute aortic syndrome during the early months of the COVID-19 pandemic in the United Kingdom.MethodsThis was a multicenter study, from March 1 to May 20, 2020 that included 19 cardiac centers, was a retrospective analysis of prospectively collected data obtained from individual centers' national cardiac surgical databases. Demographic details, choice of treatment, operative details, and outcomes were collected. COVID-19 screening, timing of surgery, and outcomes of COVID-19-positive and -negative patients were also analyzed.ResultsIn total, 88 patients presented with acute aortic syndrome to participating centers from March 1 to May 20, 2020. There were 79 aortic dissections (89.8%), 7 intramural hematomas (7.9%), and 2 penetrating aortic ulcers (2.3%). Seventy-nine patients (89.8%) underwent surgery. In-hospital mortality was 25.3% (n = 20). Postoperative complications included 13.9% postoperative stroke (11.4% permanent and 2.3% temporary), 16.5% rate of hemofiltration, and 10.1% rate of tracheostomy. Nine patients were treated conservatively with a mortality of 60%. Seven patients were diagnosed with COVID-19, and there was no associated mortality.ConclusionsDespite extensive restructuring of health care resources, access to emergency and urgent treatment for patients with acute aortic syndrome was maintained in the early months of the COVID-19 pandemic in the United Kingdom. Clinical outcomes were similar to the prepandemic period.
| S-EPMC7690305 | biostudies-literature