Browsing by Subject "Bicuspid aortic valve"

Now showing 1 - 4 of 4
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    Characterization of the Rate of Aortic Dilation in Young Patients with Thoracic Aortic Aneurysm
    (Springer, 2021) Wheeler, Adam P.; Yang, Ziyi; Cordes, Timothy M.; Markham, Larry W.; Landis, Benjamin J.; Pediatrics, School of Medicine
    Longitudinal changes in aortic diameters of young patients with thoracic aortic aneurysm (TAA) have not been completely described, particularly over long periods of follow-up. This retrospective study sought to characterize the rates of proximal aortic dilation in young patients, identify risk factors for TAA progression, and evaluate the predictive utility of early echocardiographic follow-up. Inclusion criteria were: (1) TAA or TAA-predisposing genetic diagnosis, (2) age < 25 years at first echocardiogram, and (3) minimum of 5 years of echocardiographic follow-up. Proximal aortic diameters were measured by echocardiography and Z-scores calculated to index for body surface area. TAA severity was classified as no TAA (Z-score < 2), mild (Z-score 2 to 4), or at least moderate (Z-score > 4). Among 141 included patients, mean age at first echocardiogram was 7.3 ± 3.5 years. Mean follow-up duration was 9.8 ± 3.5 years. Fifty five patients had a genetic syndrome, and 38 of the non-syndromic patients had bicuspid aortic valve (BAV). The rate of aortic dilation was significantly higher at the ascending aorta than other aortic segments. BAV and age > 10 years at first echocardiogram were associated with increased rate of ascending aorta dilation. At the ascending aorta, over 25% of patients had categorical increase in TAA severity between first and last echocardiograms, and such patients demonstrated higher rate of dilation within their first 2 years of follow-up. These longitudinal findings highlight progressive ascending aorta dilation in young patients, which may worsen around adolescence. This may help determine timing of follow-up and target ages for clinical trials.
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    Dual Coronary-Pulmonary Artery Fistula in a Patient with Severe Bicuspid Aortic Valve Stenosis
    (Houston Methodist DeBakey Heart & Vascular Center, 2023-04-10) Bou Chaaya, Rody G.; Sammour, Yasser; Thakkar, Samarthkumar; Jaradat, Ziad; Gill, William J.; Batal, Omar; Medicine, School of Medicine
    A 62-year-old male presented to the emergency department with acute viral bronchitis and worsening of his chronic dyspnea on exertion. Incidentally, a murmur was detected on physical examination. Extensive work-up, including coronary computed tomography angiography, revealed a rare combination and potential association between severe bicuspid aortic valve stenosis and coronary-pulmonary artery fistulas.
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    Identification of a common polymorphism in COQ8B acting as a modifier of thoracic aortic aneurysm severity
    (Elsevier, 2022-01-13) Landis, Benjamin J.; Lai, Dongbing; Guo, Dong-Chuan; Corvera, Joel S.; Idrees, Muhammad T.; Stadler, Henry W.; Cuevas, Christian; Needler, Gavin U.; Vujakovich, Courtney E.; Milewicz, Dianna M.; Hinton, Robert B.; Ware, Stephanie M.; Pediatrics, School of Medicine
    Thoracic aortic aneurysm (TAA) predisposes to sudden, life-threatening aortic dissection. The factors that regulate interindividual variability in TAA severity are not well understood. Identifying a molecular basis for this variability has the potential to improve clinical risk stratification and advance mechanistic insight. We previously identified COQ8B, a gene important for biosynthesis of coenzyme Q, as a candidate genetic modifier of TAA severity. Here, we investigated the physiological role of COQ8B in human aortic smooth muscle cells (SMCs) and further tested its genetic association with TAA severity. We find COQ8B protein localizes to mitochondria in SMCs, and loss of mitochondrial COQ8B leads to increased oxidative stress, decreased mitochondrial respiration, and altered expression of SMC contractile genes. Oxidative stress and mitochondrial cristae defects were prevalent in the medial layer of human proximal aortic tissues in patients with TAA, and COQ8B expression was decreased in TAA SMCs compared with controls. A common single nucleotide polymorphism (SNP) rs3865452 in COQ8B (c.521A>G, p.H174R) was associated with decreased rate of aortic root dilation in young patients with TAA. In addition, the SNP was less frequent in a second cohort of early-onset thoracic aortic dissection cases compared with controls. COQ8B protein levels in aortic SMCs were increased in TAA patients homozygous for rs3865452 compared with those homozygous for the reference allele. Thus, COQ8B is important for aortic SMC metabolism, which is dysregulated in TAA, and rs3865452 may decrease TAA severity by increasing COQ8B level. Genotyping rs3865452 may be useful for clinical risk stratification and tailored aortopathy management.
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    A Novel Human Biospecimen Repository for Clinical and Molecular Investigation of Thoracic Aortopathy
    (MDPI, 2021-09) Vujakovich, Courtney E.; Landis, Benjamin J.; Medical and Molecular Genetics, School of Medicine
    Thoracic aortic aneurysm (TAA) is a heritable aortopathy with significant morbidity and mortality, affecting children and adults. Genetic causes, pathobiological mechanisms, and prognostic markers are incompletely understood. In 2015, the Collaborative Human Aortopathy Repository (CHAR) was created to address these fundamental gaps. Patients with thoracic aortopathy, associated genetic diagnoses, or aortic valve disease are eligible for prospective enrollment. Family members and controls are also enrolled. Detailed clinical and family data are collected, and blood and aortic tissue biospecimens are processed for broad usage. A total of 1047 participants were enrolled. The mean age in 834 affected participants was 47 ± 22 (range <1 to 88) years and 580 were male (70%). A total of 156 (19%) were under the age of 21 years. Connective tissue diagnoses such as Marfan syndrome were present in 123 (15%). Unaffected participants included relatives (N = 176) and healthy aorta tissue controls (N = 37). Aortic or aortic valve biospecimens were acquired from over 290 and 110 participants, respectively. RNA and protein were extracted from cultured aortic smooth muscle cells (SMCs) for 90 participants. Over 1000 aliquots of aortic SMCs were cryopreserved. The CHAR’s breadth, robust biospecimen processing, and phenotyping create a unique, multipronged resource to accelerate our understanding of human aortopathy.