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Frontiers in Cardiovascular Medicine 2024Ascending thoracic aortic aneurysms arise from pathological tissue remodeling that leads to abnormal wall dilation and increases the risk of fatal dissection/rupture....
INTRODUCTION
Ascending thoracic aortic aneurysms arise from pathological tissue remodeling that leads to abnormal wall dilation and increases the risk of fatal dissection/rupture. Large variability in disease manifestations across family members who carry a causative genetic variant for thoracic aortic aneurysms suggests that genetic modifiers may exacerbate clinical outcomes. Decreased perlecan expression in the aorta of mgΔ mice with severe Marfan syndrome phenotype advocates for exploring perlecan-encoding as a candidate modifier gene.
METHODS
To determine the effect of concurrent and mutations on the progression of thoracic aortopathy, we characterized the microstructure and passive mechanical response of the ascending thoracic aorta in female mice of four genetic backgrounds: wild-type, heterozygous with a mutation in the gene (mgΔ), heterozygous with a mutation in the gene (), and double mutants carrying both the and variants (dMut).
RESULTS
Elastic fiber fragmentation and medial disarray progress from the internal elastic lamina outward as the ascending thoracic aorta dilates in mgΔ and dMut mice. Concurrent increase in total collagen content relative to elastin reduces energy storage capacity and cyclic distensibility of aortic tissues from mice that carry the variant. Inherent circumferential tissue stiffening strongly correlates with the severity of aortic dilatation in mgΔ and dMut mice. Perlecan haploinsufficiency superimposed to the mgΔ mutation curbs the viability of dMut mice, increases the occurrence of aortic enlargement, and reduces the axial stretch in aortic tissues.
DISCUSSION
Overall, our findings show that dMut mice are more vulnerable than mgΔ mice without an mutation, yet later endpoints and additional structural and functional readouts are needed to identify causative mechanisms.
PubMed: 38545339
DOI: 10.3389/fcvm.2024.1319164 -
Journal of Clinical Medicine Mar 2024Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave...
Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave the way they do in other cardiovascular pathologies. EMMPRIN is shed into the circulation through the secretion of extracellular vesicles. This has been demonstrated to be dependent upon the Membrane Type-1 MMP (MT1-MMP). We investigated this relationship in MFS TAA tissue and plasma to discern why unique profiles may exist. : Protein targets were measured in aortic tissue and plasma from MFS patients with TAAs and were compared to healthy controls. The abundance and location of MT1-MMP was modified in aortic fibroblasts and secreted EMMPRIN was measured in conditioned culture media. : EMMPRIN levels were elevated in MFS TAA tissue but reduced in plasma, compared to the controls. Tissue EMMPRIN elevation did not induce MMP-3, MMP-8, or TIMP-1 expression, while MT1-MMP and TIMP-2 were elevated. MMP-2 and MMP-9 were reduced in TAA tissue but increased in plasma. In aortic fibroblasts, EMMPRIN secretion required the internalization of MT1-MMP. : In MFS, impaired EMMPRIN secretion likely contributes to higher tissue levels, influenced by MT1-MMP cellular localization. Low EMMPRIN levels, in conjunction with other MMP analytes, distinguished MFS TAAs from controls, suggesting diagnostic potential.
PubMed: 38541774
DOI: 10.3390/jcm13061548 -
BMC Cardiovascular Disorders Mar 2024To evaluate the early and mid-term outcomes of open repair in patients with thoracoabdominal aortic aneurysm (TAAA) after thoracic endovascular aortic repair (TEVAR).
OBJECTIVE
To evaluate the early and mid-term outcomes of open repair in patients with thoracoabdominal aortic aneurysm (TAAA) after thoracic endovascular aortic repair (TEVAR).
METHODS
This was a retrospective single center study. Data were retrospectively collected and analyzed for consecutive patients undergoing open TAAA repair (TAAAR) after TEVAR from November 2016 to June 2021. Indications for TAAAR included aneurysm progression due to endoleak, persisted false lumen perfusion, proximal/distal disease progression, and aorta rupture. The risk factor of operative mortality was analyzed by multivariable logistic regression model and the survival was evaluated by Kaplan-Meier.
RESULTS
Sixty-three patients who met the inclusion criteria for the study were identified. The mean age at TAAAR was 41 ± 12 years and 43 (68.3%) were male. Marfan syndrome (MFS) was presented in 39 patients (61.9%). 60 (95.2%) patients presented with post-dissection aneurysm and 3 (4.8%) patients with degenerative aneurysm. The extent of TAAA was Crawford I in 9 (14.3%), II in 22 (34.9%), III in 23 (36.5%), and IV in 9 (14.3%). Emergent TAAAR was done in 10 (15.9%) patients, and deep hypothermic circulatory arrest was used in 22 (34.6%). Endograft was explanted in 31 (49.2%). Operative mortality was 11 (17.5%). Stroke, paraplegia, and acute kidney failure occurred in 5 (7.9%), 7 (11.1%), and 6 (9.5%) patients, respectively. Pulmonary complications occurred in 19 (30.2%) patients. The estimated survival was 74.8 ± 4.9% at 5 years. Late reoperations were performed in 2 patients at 2.5 years and 1.3 years, respectively.
CONCLUSIONS
In this series of TAAA after TEVAR, TAAAR was related with a high risk of operative mortality and morbidity and the midterm outcomes represented a durable treatment and were respectable.
Topics: Humans; Male; Female; Endovascular Aneurysm Repair; Blood Vessel Prosthesis; Retrospective Studies; Blood Vessel Prosthesis Implantation; Aortic Aneurysm, Thoracoabdominal; Treatment Outcome; Aortic Aneurysm, Thoracic; Risk Factors; Endovascular Procedures; Postoperative Complications
PubMed: 38532333
DOI: 10.1186/s12872-024-03837-8 -
Cureus Feb 2024Marfan syndrome (MFS) presents complex cardiovascular manifestations and challenges in management due to its impact on multiple body systems. This case study examines...
Marfan syndrome (MFS) presents complex cardiovascular manifestations and challenges in management due to its impact on multiple body systems. This case study examines the clinical profile, diagnostic findings, and physiotherapy intervention for a 57-year-old male with MFS who experienced severe aortic and mitral valvular complications. The patient's admission was marked by fatigue, reduced mobility, breathlessness, and a confirmed diagnosis of MFS. Cardiac evaluation revealed severe regurgitation and aortic root dilation. The patient's symptoms were exhaustion, giddiness, dyspnea, and decreased mobility. The objective of this case study was to describe the impact of graded mobilization and pacing techniques in maximizing functional mobility and alleviating symptoms associated with aortic regurgitation and aortic root dilatation through an extensive physiotherapy program. Exercises addressing dyspnea, lung capacity, posture, functional mobility, and fatigue reduction were included in the physiotherapy intervention. The rehabilitation outcome showed a notable shift of score from 3 to 0.5 on the Borg scale of dyspnea, indicating enhanced functional capacity and improved quality of life. Post-rehabilitation, the patient exhibited significant progress in the two-minute walk test. This case highlights the importance of tailored interventions in managing MFS-related cardiac complications.
PubMed: 38524030
DOI: 10.7759/cureus.54591 -
Archivos de Cardiologia de Mexico 2024Ascending aortic aneurysms are rare pathologies in childhood, especially in the absence of previous diseases such as Marfan syndrome.
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.
Topics: Humans; Child; Aneurysm, Aortic Arch; Aortic Aneurysm; Stents; Aneurysm, False; Treatment Outcome; Endovascular Procedures; Aortic Aneurysm, Thoracic
PubMed: 38507313
DOI: 10.24875/ACM.22000272 -
Translational Vision Science &... Mar 2024To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data.
PURPOSE
To derive an effective nomogram for predicting Marfan syndrome (MFS) in children with congenital ectopia lentis (CEL) using regularly collected data.
METHODS
Diagnostic standards (Ghent nosology) and genetic test were applied in all patients with CEL to determine the presence or absence of MFS. Three potential MFS predictors were tested and chosen to build a prediction model using logistic regression. The predictive performance of the nomogram was validated internally through time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis.
RESULTS
Eyes from 103 patients under 20 years old and with CEL were enrolled in this study. Z score of body mass index (odds ratio [OR] = 0.659; 95% confidence interval [CI], 0.453-0.958), corneal curvature radius (OR = 3.397; 95% CI, 1.829-6.307), and aortic root diameter (OR = 2.342; 95% CI, 1.403-3.911) were identified as predictors of MFS. The combination of the above predictors shows good predictive ability, as indicated by area under the curve of 0.889 (95% CI, 0.826-0.953). The calibration curves showed good agreement between the prediction of the nomogram and the actual observations. In addition, decision curve analysis showed that the nomogram was clinically useful and had better discriminatory power in identifying patients with MFS. For better individual prediction, an online MFS calculator was created.
CONCLUSIONS
The nomogram provides accurate and individualized prediction of MFS in children with CEL who cannot be identified with the Ghent criteria, enabling clinicians to personalize treatment plans and improve MFS outcomes.
TRANSLATIONAL RELEVANCE
The prediction model may help clinicians identify MFS in its early stages, which could reduce the likelihood of developing severe symptoms and improve MFS outcomes.
Topics: Child; Humans; Young Adult; Adult; Ectopia Lentis; Marfan Syndrome; Nomograms; Eye
PubMed: 38502141
DOI: 10.1167/tvst.13.3.15 -
Research Square Mar 2024We performed a secondary analysis of the Pediatric Heart Network Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and...
We performed a secondary analysis of the Pediatric Heart Network Marfan Trial public-use database to evaluate associations between extracardiac features and cardiac and aortic phenotypes in study participants. Aortic aneurysm phenotype was defined as aortic root Z-score ≥ 4.5, aortic root growth rate ≥ 75th percentile, aortic dissection, and aortic surgery. Severe cardiac phenotype was defined as aortic dissection, aortic Z-score ≥4.5, aortic valve surgery, at least moderate mitral regurgitation, mitral valve surgery, left ventricular dysfunction, or death. Extracardiac manifestations were characterized by specific organ system involvement and by a novel aggregate extracardiac score that was created for this study based on the original Ghent nosology. Logistic regression analysis compared aggregate extracardiac score and systems involvement to outcomes. Of 608 participants (60% male), the median age at enrollment was 10.8 years (interquartile range: 6, 15.4). Aortic aneurysm phenotype was observed in 71% of participants and 64% had severe cardiac phenotype. On univariate analysis, skeletal (OR: 1.95, 95% CI: 1.01, 3.72; p = 0.05), skin manifestation (OR: 1.62, 95% CI: 1.13, 2.34; p = 0.01) and aggregate extracardiac score (OR: 1.17, 95% CI: 1.02, 1.34; p = 0.02) were associated with aortic aneurysm phenotype but were not significant in multivariate analysis. There was no association between extracardiac manifestations and severe cardiac phenotype. Thus, the severity of cardiac manifestations in Marfan syndrome was independent of extracardiac phenotype and aggregate extracardiac score. Severity of extracardiac involvement did not appear to be a useful clinical marker for cardiovascular risk-stratification in this cohort of children and young adults with Marfan syndrome.
PubMed: 38496659
DOI: 10.21203/rs.3.rs-3994693/v1 -
Methodist DeBakey Cardiovascular Journal 2024Thoracic aortic disease (TAD) poses substantial risks during pregnancy, particularly for women with genetic conditions such as Marfan syndrome, Loeys-Dietz syndrome, and... (Review)
Review
Thoracic aortic disease (TAD) poses substantial risks during pregnancy, particularly for women with genetic conditions such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome. This review examines the epidemiology, risk assessment, and management of TAD in pregnancy. Preconception counseling is vital considering the hereditary nature of TAD and potential pregnancy-related complications. Genetic testing and imaging surveillance aid in risk assessment. Medical management, including beta-blockade and strict blood pressure control, is essential throughout pregnancy. Surgical interventions may be necessary in certain cases. A multidisciplinary approach involving cardiologists, obstetricians, cardiac surgeons, anesthesiologists, and other specialists with expertise in cardio-obstetrics is essential for optimal outcomes. Patient education and shared decision-making play vital roles in navigating the complexities of TAD in pregnancy and improving maternal and neonatal outcomes.
Topics: Pregnancy; Infant, Newborn; Humans; Female; Aortic Diseases; Aorta; Loeys-Dietz Syndrome; Marfan Syndrome; Risk Assessment
PubMed: 38495666
DOI: 10.14797/mdcvj.1371 -
Cureus Feb 2024Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural... (Review)
Review
Marfan syndrome (MFS) is a progressive connective tissue disease with a broad range of clinical manifestations. We sought to establish the spectrum of structural valvular abnormalities as cardiovascular involvement has been identified as the most life-threatening aspect of the syndrome. This was a systematic review with a meta-analysis of studies indexed in Medline from the inception of the database to November 7, 2022. Using the random-effects model, separate Forest and Galbraith plots were generated for each valvular abnormality assessed. Heterogeneity was assessed using the statistics whilst funnel plots and Egger's test were used to assess for publication bias. From a total of 35 studies, a random-effects meta-analysis approximated the pooled summary estimates for the prevalence of cardiac valve abnormalities as mitral valve prolapse 65% (95% CI: 57%-73%); mitral valve regurgitation 40% (95% CI: 29%-51%); aortic valve regurgitation 40% (95% CI: 28%-53%); tricuspid valve prolapse 35% (95% CI: 15%-55%); and tricuspid valve regurgitation 43% (95% CI: 8%-78%). Only one study reported on the involvement of the pulmonary valve (pulmonary valve prolapse was estimated at 5.3% (95% CI: 1.9%-11.1%) in a cohort of 114 patients with MFS). We believe this study provides a description of the structural valvular disease spectrum and may help inform providers and patients in understanding the clinical history of MFS in the current treatment era with its increased life expectancy.
PubMed: 38487153
DOI: 10.7759/cureus.54141 -
International Journal of Molecular... Feb 2024Mutations of the gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is...
Mutations of the gene lead to Marfan syndrome (MFS), which is an autosomal dominant connective tissue disorder featured by thoracic aortic aneurysm risk. There is currently no effective treatment for MFS. Here, we studied the role of mitochondrial dysfunction in the phenotypic transformation of human smooth muscle cells (SMCs) and whether a mitochondrial boosting strategy can be a potential treatment. We knocked down in SMCs to create an MFS cell model and used rotenone to induce mitochondrial dysfunction. Furthermore, we incubated the SMCs with Coenzyme Q10 (CoQ10) to assess whether restoring mitochondrial function can reverse the phenotypic transformation. The results showed that SMCs had decreased (mitochondrial transcription factor A), mtDNA levels and mitochondrial mass, lost their contractile capacity and had increased synthetic phenotype markers. Inhibiting the mitochondrial function of SMCs can decrease the expression of contractile markers and increase the expression of synthetic genes. Imposing mitochondrial stress causes a double-hit effect on the level, oxidative phosphorylation and phenotypic transformation of -knockdown SMCs while restoring mitochondrial metabolism with CoQ10 can rapidly reverse the synthetic phenotype. Our results suggest that mitochondria function is a potential therapeutic target for the phenotypic transformation of SMCs in MFS.
Topics: Humans; Marfan Syndrome; Phenotype; Myocytes, Smooth Muscle; Mitochondrial Diseases; Fibrillin-1; Adipokines; Ubiquinone
PubMed: 38473909
DOI: 10.3390/ijms25052662