scholarly journals Genetic Insights into Bicuspid Aortic Valve Formation

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Brigitte Laforest ◽  
Mona Nemer

Bicuspid aortic valve (BAV) is the most common congenital heart defect, affecting 1-2% of the population. It is generally diagnosed late in adulthood when deterioration of the abnormal leaflet becomes clinically evident. BAV patients have an increased risk of developing serious complications, including stenosis, regurgitation, endocarditis, dilation of the aorta, aortic dissection, and aneurysm. BAV is a heritable trait, but the genetic basis underlying this cardiac malformation remains poorly understood. In the last decade, thanks to studies in animal models as well as genetic and biochemical approaches, a large number of genes that play important roles in heart development have been identified. These discoveries provided valuable insight into cardiac morphogenesis and uncovered congenital-heart-disease-causing genes. This paper will summarize the current knowledge of valve morphogenesis as well as our current understanding of the genetic pathways involved in BAV formation. The impact of these advances on human health including diagnosis of BAV and prevention of cardiovascular complications in individuals with BAV or with a family history of BAV is also discussed.

2006 ◽  
Vol 91 (5) ◽  
pp. 1785-1788 ◽  
Author(s):  
Carolyn A. Bondy ◽  
Phillip L. Van ◽  
Vladimir K. Bakalov ◽  
Vincent B. Ho

Background: In recent years many girls with Turner syndrome (TS) have been treated with supraphysiological doses of GH to increase adult height. In addition to promoting statural growth, GH may have direct effects on the cardiovascular system. Objective: We sought to determine whether GH treatment affects aortic diameter in girls with TS because there is an increased risk for aortic dilation and dissection in this syndrome. Methods: In a retrospective, cross-sectional study, we compared ascending and descending aortic diameters measured by magnetic resonance imaging in GH-treated (n = 53) vs. untreated (n = 48) patients with TS participating in a National Institutes of Health protocol between 2001 and 2004. Results: The average duration of GH treatment was 4.7 with se 0.4 yr (range 2–11 yr). The two groups were similar in age and weight, but GH-treated subjects were on average 8 cm taller (P = 0.002). The diameter of the ascending aorta was increased by 7.3% and descending aorta by 8.9% in the GH-treated group. However, after correction for age, height, weight, and presence of bicuspid aortic valve and coarctation, using a multiple regression, neither history of GH treatment nor the length of GH treatment had an effect on the aortic diameter. Weight (P = 0.02), height (P = 0.001), and presence of bicuspid aortic valve (P = 0.0001) were associated with larger ascending aortic diameter, whereas age (P = 0.008), height (P = 0.02), and history of coarctation (P = 0.006) were associated with larger descending aortic diameter. Conclusions: GH treatment of girls with TS does not seem to affect ascending or descending aortic diameter above the increase related to the larger body size.


2021 ◽  
Vol 12 ◽  
Author(s):  
Jing Wang ◽  
Wenhui Deng ◽  
Qing Lv ◽  
Yuman Li ◽  
Tianshu Liu ◽  
...  

Bicuspid aortic valve (BAV) is the most common congenital cardiac abnormality. BAV aortic dilatation is associated with an increased risk of adverse aortic events and represents a potentially lethal disease and hence a considerable medical burden. BAV with aortic dilatation warrants frequent monitoring, and elective surgical intervention is the only effective method to prevent dissection or rupture. The predictive value of the aortic diameter is known to be limited. The aortic diameter is presently still the main reference standard for surgical intervention owing to the lack of a comprehensive understanding of BAV aortopathy progression. This article provides a brief comprehensive review of the current knowledge on BAV aortopathy regarding clinical definitions, epidemiology, natural course, and pathophysiology, as well as hemodynamic and clinically significant aspects on the basis of the limited data available.


Author(s):  
Naresh Dhawan ◽  
Rohin Kumar ◽  
Reema Kumar Bhatt

Cardiac disease in pregnancy is a leading cause of maternal death in more so high-income countries. The armamentarium for winning this difficult battle involves shared decision-making with communication across the clinical team and the patient. There is limited clinical evidence concerning effective approaches to managing such complex care and moreover involvement of different specialists makes coordinated care challenging. Bicuspid aortic valve (BAV) is the most common congenital cardiac malformation, occurring in 1-2% of the population whereas a single ventricle is a rare congenital heart disease that accounts for less than 1% of all congenital heart diseases. We had two cases of pregnancy with bicuspid aortic valve in one case and the other with single ventricle. The involvement of multidisciplinary team involving cardiologist, cardiothoracic anaesthetist and fetal maternal medicine specialist resulted in good maternal and fetal outcome in both the cases.


Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4220
Author(s):  
Massimo Chessa ◽  
Mario Panebianco ◽  
Sara Corbu ◽  
Milena Lussu ◽  
Angelica Dessì ◽  
...  

Bicuspid aortic valve (BAV) is the most common congenital heart defect responsible for valvular and aortic complications in affected patients. Causes and mechanisms of this pathology are still elusive and thus the lack of early detection biomarkers leads to challenges in its diagnosis and prevention of associated cardiovascular anomalies. The aim of this study was to explore the potential use of urine Nuclear Magnetic Resonance (NMR) metabolomics to evaluate a molecular fingerprint of BAV. Both multivariate and univariate statistical analyses were performed to compare the urinary metabolome of 20 patients with BAV with that of 24 matched controls. Orthogonal partial least squared discriminant analysis (OPLS-DA) showed statistically significant discrimination between cases and controls, suggesting seven metabolites (3-hydroxybutyrate, alanine, betaine, creatine, glycine, hippurate, and taurine) as potential biomarkers. Among these, glycine, hippurate and taurine individually displayed medium sensitivity and specificity by receiver operating characteristic (ROC) analysis. Pathway analysis indicated two metabolic pathways likely perturbed in BAV subjects. Possible contributions of gut microbiota activity and energy imbalance are also discussed. These results constitute encouraging preliminary findings in favor of the use of urine-based metabolomics for early diagnosis of BAV.


Author(s):  
Annamaria Biczok ◽  
Philipp Karschnia ◽  
Raffaela Vitalini ◽  
Markus Lenski ◽  
Tobias Greve ◽  
...  

Abstract Background Prognostic markers for meningioma recurrence are needed to guide patient management. Apart from rare hereditary syndromes, the impact of a previous unrelated tumor disease on meningioma recurrence has not been described before. Methods We retrospectively searched our database for patients with meningioma WHO grade I and complete resection provided between 2002 and 2016. Demographical, clinical, pathological, and outcome data were recorded. The following covariates were included in the statistical model: age, sex, clinical history of unrelated tumor disease, and localization (skull base vs. convexity). Particular interest was paid to the patients’ past medical history. The study endpoint was date of tumor recurrence on imaging. Prognostic factors were obtained from multivariate proportional hazards models. Results Out of 976 meningioma patients diagnosed with a meningioma WHO grade I, 416 patients fulfilled our inclusion criteria. We encountered 305 women and 111 men with a median age of 57 years (range: 21–89 years). Forty-six patients suffered from a tumor other than meningioma, and no TERT mutation was detected in these patients. There were no differences between patients with and without a positive oncological history in terms of age, tumor localization, or mitotic cell count. Clinical history of prior tumors other than meningioma showed the strongest association with meningioma recurrence (p = 0.004, HR = 3.113, CI = 1.431–6.771) both on uni- and multivariate analysis. Conclusion Past medical history of tumors other than meningioma might be associated with an increased risk of meningioma recurrence. A detailed pre-surgical history might help to identify patients at risk for early recurrence.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Victoria Hale ◽  
Maren Weischer ◽  
Jong Y. Park

Although the causes of prostate cancer are largely unknown, previous studies support the role of genetic factors in the development of prostate cancer.CHEK2plays a critical role in DNA replication by responding to double-stranded breaks. In this review, we provide an overview of the current knowledge of the role of a genetic variant, 1100delC, ofCHEK2on prostate cancer risk and discuss the implication for potential translation of this knowledge into clinical practice. Currently, twelve articles that discussedCHEK2∗1100delC and its association with prostate cancer were identified. Of the twelve prostate cancer studies, five studies had independent data to draw conclusive evidence from. The pooled results of OR and 95% CI were 1.98 (1.23–3.18) for unselected cases and 3.39 (1.78–6.47) for familial cases, indicating thatCHEK2∗1100delC mutation is associated with increased risk of prostate cancer. Screening for CHEK2∗1100delC should be considered in men with a familial history of prostate cancer.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jay D Pal ◽  
Charles T Klodell ◽  
Ranjit John ◽  
Francis Pagani ◽  
Joseph G Rogers ◽  
...  

Objective: Our goal was to determine the operative mortality of isolated implantation of the HeartMate II continuous flow LVAD and the impact of additional concurrent cardiac procedures on patient outcomes. Methods: In a multicenter trial, 279 patients at 33 clinical sites underwent implantation of the HeartMate II continuous flow LVAD as a bridge to transplantation from March 2005 to March 2007. HeartMate II implantation (HM II) was the only procedure required in 172 patients while 80 patients required concurrent cardiac procedures in conjunction with LVAD implantation (HM II+CCP). Results: Preoperative characteristics were similar, but central venous pressure (14.5 vs 11.6 mmHg) was greater for patients requiring concurrent cardiac procedures, suggesting worse right heart dysfunction. Mean cardiopulmonary bypass times increased from 97 to 120 minutes when a concurrent cardiac procedure was performed (p<0.001). Length of stay slightly increased from 23 to 26 days (p=0.17). Overall 30- and 180-day mortality was 5.8% and 13.3% for the HM II group, and 11.3% and 20.0% for the HM II+CCP group. Concurrent valvular procedures increased the risk to 8.5% and 19.1%. Patients who underwent an aortic valve replacement with cardioplegic arrest had a 30-day mortality of 25%, higher than for isolated concurrent mitral (0%) or tricuspid repair (3.3%). Other cardiac procedures were associated with a 30-day mortality of 27.8%. Survival at 180 days was 87% for HMII alone and 80% for HMII+CCP. Conclusion: There is a low 5.8% operative mortality for patients requiring uncomplicated HeartMate II implantation, with no apparent increased risk for concurrent PFO closure, mitral or tricuspid repair. However, concurrent aortic valve and other cardiac procedures are associated with a significantly decreased survival. The increased risk of these procedures must be balanced against the negative impact of uncorrected aortic insufficiency during VAD support.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A922-A923
Author(s):  
Sandhya Bassin ◽  
Louis F Amorosa

Abstract Background: Thyrotoxicosis can be mistaken for conditions such as atrial fibrillation and pulmonary embolism (PE) given the nonspecific symptoms of fatigue, palpitations, and dyspnea. Patients often undergo further imaging on presentation to the emergency room (ER), many of which use iodine for contrast. This can put patients at increased risk for iodine induced hyperthyroidism and delay definitive treatment in patients with Graves’ disease, the most common cause of hyperthyroidism. Clinical Case: A 53-year-old male with history of hyperthyroidism, atrial fibrillation, and prior PE presented with palpitations to the ER. He developed worsening dyspnea on exertion and palpitations over the last three days. He was unable to afford his medications, including methimazole, for the last nine months. In the ER he was in atrial fibrillation with rapid ventricular response. Due to concern for PE, he underwent a CTA with contrast, which was negative. His physical exam was notable for a diffusely enlarged goiter. His labs showed low TSH &lt;0.01 (norm 0.35-5.50mIU/L) and high free T4 &gt;7.77 (norm 0.9-1.8ng/dL). TSH stimulating antibodies were elevated at 1.9 (norm &lt;1.3 TSI index), consistent with Graves’ hyperthyroidism. Endocrinology was then consulted for severe thyrotoxicosis, initially treating the patient with PTU and propranolol. The patient was transitioned to methimazole and continued propranolol on discharge. Since he was given contrast, plan was for repeat thyroid uptake scan and iodine ablation in 3 months. However, patient was not compliant with medications, resulting in readmission for thyrotoxicosis 3 months later. Conclusion: This case highlights the impact of increased use of contrast in imaging in hyperthyroid patients. Hyperthyroid patients are at an increased risk for emboli. However, iodine can cause contrast-induced hyperthyroidism and delay definitive treatment of Graves’ disease. As almost half of thyrotoxic patients receive iodinated contrast prior to an endocrine consultation, endocrinologists should work with emergency physicians to develop a set of guidelines to identify at risk populations for hyperthyroidism (1). We advocate for urgent thyroid testing in patients with new onset atrial fibrillation, a history of Graves’ disease, specific symptoms of Graves’, or those taking thyrotoxic-inducing medications. This will assist in determining if patients should receive a prophylactic dose of anti-thyroid medication prior to iodinated contrast imaging. These guidelines can help prevent contrast induced hyperthyroidism and disruptions in treatment of Graves’ while still imaging patients for other diagnoses on the differential. Reference: (1) Giacomini A, et al. Urgent thyroid-stimulating hormone testing in emergency medicine: A useful tool? J Emerg Med. 2015;49(4):481-487.


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