Familial patent ductus arteriosus and bicuspid aortic valve with hand anomalies: a novel heart-hand syndrome.

The association between cardiac and limb defects, particularly those affecting the hand, has been well documented by the delineation of several heart-hand syndromes. Based on observations with a three-generation family with seven affected individuals, we describe a novel heart-hand syndrome comprising patent ductus arteriosus, bicuspid aortic valve, 5th metacarpal hypoplasia, and brachydactyly. The inheritance pattern was consistent with autosomal dominance, although X-linked dominance could not be excluded. Penetrance appeared to be complete, but there was variability of the cardiac and hand phenotypes. Because this new syndrome closely resembled Char syndrome (patent ductus arteriosus, 5th finger middle phalangeal hypoplasia, and minor facial anomalies), multipoint linkage analysis was performed using polymorphic DNA markers spanning the recently identified Char syndrome critical region at chromosomal bands 6p12-p21.1. This analysis formally excluded this 3-cM region, documenting that the two traits are not allelic. In sum, a novel heart-hand syndrome involving left ventricular outflow and aortic arch as well as an ulnar ray derivative has been identified. Because the hand anomalies can be subtle, thorough evaluation is suggested for families inheriting these cardiac defects as a mendelian trait.     

Familial patent ductus arteriosus and bicuspid aortic valve with hand anomalies: A novel heart-hand syndrome

The association between cardiac and limb defects, particularly those affecting the hand, has been well documented by the delineation of several heart-hand syndromes. Based on observations with a three-generation family with seven affected individuals, we describe a novel heart-hand syndrome comprising patent ductus arteriosus, bicuspid aortic valve, 5th metacarpal hypoplasia, and brachydactyly. The inheritance pattern was consistent with autosomal dominance, although X-linked dominance could not be excluded. Penetrance appeared to be complete, but there was variability of the cardiac and hand phenotypes. Because this new syndrome closely resembled Char syndrome (patent ductus arteriosus, 5th finger middle phalangeal hypoplasia, and minor facial anomalies), multipoint linkage analysis was performed using polymorphic DNA markers spanning the recently identified Char syndrome critical region at chromosomal bands 6p12–p21.1. This analysis formally excluded this 3-cM region, documenting that the two traits are not allelic. In sum, a novel heart-hand syndrome involving left ventricular outflow and aortic arch as well as an ulnar ray derivative has been identified. Because the hand anomalies can be subtle, thorough evaluation is suggested for families inheriting these cardiac defects as a mendelian trait. Am. J. Med. Genet. 87:175–179, 1999. © 1999 Wiley-Liss, Inc.     

Familial patent ductus arteriosus: A further case of CHAR syndrome

We report on a family with patent ductus arteriosus, a distinctive facial appearance with eyebrow flare, a short nose and “duck-bill lips,” polydactyly, and fifth finger clinodactyly. The facial traits were consistent with CHAR syndrome. We provide further evidence for evolution of the phenotype with age and describe the previously unreported finding of interstitial polydactyly in this syndrome. Am. J. Med. Genet. 71:229–232, 1997. © 1997 Wiley-Liss, Inc.     

覆膜支架在主动脉缩窄合并动脉导管未闭时的应用指征

先天性主动脉缩窄指自无名动脉至第一对肋间动脉之间的主动脉管腔狭窄，多为局限性，也可为长管状。主动脉缩窄占先天性心血管疾病发病率的1％～3％，本病可单独存在，但常合并其他心血管畸形，如室间隔缺损、动脉导管未闭等。刘芳等报告的96例主动脉缩窄患者中合并室间隔缺损与动脉导管未闭患者各占49％，而室间隔缺损与动脉导管未闭同时并存者占23％。     

Gigantic patent ductus arteriosus — Report of a newborn cadaver dissection and review of the literature

Summary During the gross anatomical dissection of the thoracic region in a newborn, a gigantic patent ductus arteriosus was found. This vessel had a diameter as large as the pulmonary trunk and a longer length. The brachiocephalic a. and the left common carotid a. originated from the aortic arch in close proximity with each other. The descending aorta showed a dilatation at the junction of this large-bored patent ductus arteriosus. We were unable to find any similar case in the published literature. Knowing that the anatomical variations of the great vessels may cause confusion during surgery or evaluation of CT and MRI scans, this rare case with a huge patent ductus arteriosus is presented.

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Canal artériel géant -Rapport de la dissection d'un cadavre de nouveau-né et revue de la littérature

Résumé Lors de la dissection du thorax d'un nouveau-né, un canal artériel géant a été découvert. Ce vaisseau était de même diamètre que le tronc pulmonaire et plus long qu'elle. Le tronc brachio-céphalique et l'a. carotide commune gauche naissaient de l'arc aortique de manière très proche. L'aorte thoracique descendante était dilatée à la jonction de ce volumineux canal artériel. Nous n'avons pas trouvé de cas analogue dans la littérature. Sachant que les variations des gros vaisseaux peuvent entraîner des difficultés pendant une intervention chirurgicale ou lors de l'interprétation de tomodensitométrie ou d'IRM, il nous a semblé intéressant de publier cette observation.

     

HTAADVar: Aggregation and fully automated clinical interpretation of genetic variants in heritable thoracic aortic aneurysm and dissection

PurposeEarly detection and pathogenicity interpretation of disease-associated variants are crucial but challenging in molecular diagnosis, especially for insidious and life-threatening diseases, such as heritable thoracic aortic aneurysm and dissection (HTAAD). In this study, we developed HTAADVar, an unbiased and fully automated system for the molecular diagnosis of HTAAD.MethodsWe developed HTAADVar (http://htaadvar.fwgenetics.org) under the American College of Medical Genetics and Genomics/Association for Molecular Pathology framework, with optimizations based on disease- and gene-specific knowledge, expert panel recommendations, and variant observations. HTAADVar provides variant interpretation with a self-built database through the web server and the stand-alone programs.ResultsWe constructed an expert-reviewed database by integrating 4373 variants in HTAAD genes, with comprehensive metadata curated from 697 publications and an in-house study of 790 patients. We further developed an interpretation system to assess variants automatically. Notably, HTAADVar showed a multifold increase in performance compared with public tools, reaching a sensitivity of 92.64% and specificity of 70.83%. The molecular diagnostic yield of HTAADVar among 790 patients (42.03%) also matched the clinical data, independently demonstrating its good performance in clinical application.ConclusionHTAADVar represents the first fully automated system for accurate variant interpretation for HTAAD. The framework of HTAADVar could also be generalized for the molecular diagnosis of other genetic diseases.     

Percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder

OBJECTIVE:

Ventricular septal defects resulting from post-traumatic cardiac injury are very rare. Percutaneous closure has emerged as a method for treating this disorder. We wish to report our experience in three patients who underwent percutaneous closure of a post-traumatic ventricular septal defect with a patent ductus arteriosus occluder.

METHODS:

We treated three patients with post-traumatic ventricular septal defects caused by stab wounds with knives. After the heart wound was repaired, patient examinations revealed ventricular septal defects with pulmonary/systemic flow ratios (Qp/Qs) of over 1.7. The post-traumatic ventricular septal defects were closed percutaneously with a patent ductus arteriosus occluder (Lifetech Scientific (Shenzhen) Co., LTD, Guangdong, China) utilizing standard techniques.

RESULTS:

Post-operative transthoracic echocardiography revealed no residual left-to-right shunt and indicated normal ventricular function. In addition, 320-slice computerized tomography showed that the occluder was well placed and exhibited normal morphology.

CONCLUSION:

Our experiences indicate that closure of a post-traumatic ventricular septal defect using a patent ductus arteriosus occluder is feasible, safe, and effective.     

Point-of-care testing for B-type natriuretic peptide in premature neonates with patent ductus arteriosus

Patent ductus arteriosus (PDA) is highly prevalent in pre-term neonates (PTN) and has been recognized as a neonatal co-morbidity. The purpose of this study was to determine if levels of brain (or B-type) natriuretic peptide (BNP), a peptide secreted by ventricular myocytes in response to volume or pressure overload, correlate with the size of the PDA. In a prospective design, 52 PTN (no PDA: n=24; PDA: n=28) were studied after obtaining parental consent. Those with genetic anomalies and congenital heart disease, except for PDA and patent foramen ovale, were excluded. Echocardiographic estimates of the diameters of the PDA (or absence of PDA) were made concurrently with capillary blood collection for BNP assay. BNP levels in samples from PTN without PDA were 23.6 ng/L (median); 13.1 to 32.3 ng/L (IQR); initial samples (between days 3 and 7 of life) with small PDA (n=11), median 66.1 ng/L; 55.5 to 85.3 ng/L (IQR); with moderate PDA (n=6) median 284 ng/L; 204 to 622 ng/L (IQR); and with large PDA (n=11) 2410 ng/L median; 420 to 2770 ng/L (IQR). (p< 0.0001 for ANOVA; groupwise: p<0.05 for both no PDA vs. moderate and large PDA); Trend analysis suggested a strong association of BNP with size of PDA (p<0.001). Of 17 subjects with moderate to large PDA, pre and post-treatment (Ibuprofen; per standard protocol) data were obtained on 12 subjects. Pre-treatment BNP ranged from 111 to 5000 ng/L; post-treatment BNP decreased to 5.0 to 262 ng/L (p = 0.0005). Estimates of decision levels for treatment were made by examining dichotomized groups, i.e., no-to-small vs. moderate-to-large and using receiver-operator characteristic (ROC) curve analysis yielding a value of 123 ng/L. BNP may obviate repeated echocardiography as follow up after treatment, or to monitor future course of respiratory distress secondary to PDA in PTN.     

GenTAC registry report: Gender differences among individuals with genetically triggered thoracic aortic aneurysm and dissection

Previous data suggest women are at increased risk of death from aortic dissection. Therefore, we analyzed data from the GenTAC registry, the NIH‐sponsored program that collects information about individuals with genetically triggered thoracic aortic aneurysms and cardiovascular conditions. We performed cross‐sectional analyses in adults with Marfan syndrome (MFS), familial thoracic aortic aneurysm or dissection (FTAAD), bicuspid aortic valve (BAV) with thoracic aortic aneurysm or dissection, and subjects under 50 years of age with thoracic aortic aneurysm or dissection (TAAD <50 years). Women comprised 32% of 1,449 subjects and were 21% of subjects with BAV, 34% with FTAAD, 22% with TAAD <50 years, and 47% with MFS. Thoracic aortic dissections occurred with equal gender frequency yet women with BAV had more extensive dissections. Aortic size was smaller in women but was similar after controlling for BSA. Age at operation for aortic valve dysfunction, aneurysm or dissection did not differ by gender. Multivariate analysis (adjusting for age, BSA, hypertension, study site, diabetes, and subgroup diagnoses) showed that women had fewer total aortic surgeries (OR = 0.65, P < 0.01) and were less likely to receive angiotensin converting enzyme inhibitors (ACEi; OR = 0.68, P < 0.05). As in BAV, other genetically triggered aortic diseases such as FTAAD and TAAD <50 are more common in males. In women, decreased prevalence of aortic operations and less treatment with ACEi may be due to their smaller absolute aortic diameters. Longitudinal studies are needed to determine if women are at higher risk for adverse events. © 2013 Wiley Periodicals, Inc.     

Evolution of healthy thoracic aortic segment diameter during follow-up of patients with aortic aneurysm or dissection: a magnetic resonance imaging study

We studied the normal evolution over time of the diameter of the healthy descending aorta in patients suffering from aneurysm or dissection of the ascending aorta, in order to anticipate potential complications of endoprosthetic treatment in this aortic segment. During their follow-up (average 35.9 months), 52 patients suffering from aneurysm or dissection of the ascending aorta had 168 aortic MRI examinations (27; average 3). Measurements were taken according to conventional reference landmarks making it possible to study the evolution of the diameter of the supposed healthy descending thoracic aorta. The variations in diameter with time were on average 5 mm, and there was no significant variation in this diameter, either for early controls or for the controls carried out after more than 1 year or 3 years, whatever the age group. Thus according to our series it seems that patients with a descending aorta endoprosthesis are not exposed to graft endoleak due to inadequate contact of the prosthesis and aorta within the 5 years following its implantation.     

Familial supravalvular aortic stenosis: a genetic study.

Supravalvular aortic stenosis (McKusick 18550) is a rare hereditary condition with autosomal dominant transmission. However, the available data have been limited to small family groups which do not allow the definition of the degree of penetrance of the disease. The present study describes a large family with a high frequency of supravalvular aortic stenosis including five generations and 80 subjects, the largest family group with this disease studied so far. The study was carried out prospectively in 66 subjects (clinical examination, ECG, M mode and two dimensional echocardiography). In 14 subjects available data were examined retrospectively. In 10 patients cardiac catheterisation was performed (prospective study in eight). The disease was present in 36 (45%) of the 80 subjects investigated, on the basis of clinical, echocardiographic, and haemodynamic (when available) criteria. The disease was found to be severe in eight cases (22%), moderate in six cases (17%), mild in 13 (36%), and undefined in eight (22%) patients. In one case (3%), multiple pulmonary stenoses were noted in the absence of supravalvular aortic stenosis. Genetic analysis of these data shows, for the first time, the degree of penetrance of the supravalvular aortic stenosis trait (K = 0.86) and confirms that it is transmitted with incomplete penetrance and variable expressivity.     

Systematic review of quality of life in persons with hereditary thoracic aortic aneurysm and dissection diagnoses

The purpose of this study was to explore the literature on quality of life (QoL) in patients with hereditary thoracic aortic aneurysm and dissection (HTAAD); including Marfan syndrome (MFS), Loeys-Dietz syndrome (LDS), vascular Ehlers-Danlos syndrome (vEDS) and other HTAAD diagnoses, critically appraising and synthesizing the relevant literature. A systematic review was performed by searching the published literature using available medical, physical, psychological, social databases and other sources. Studies addressing QoL in persons with an HTAAD diagnosis, published in peer-reviewed journals were assessed. Of 227 search results, 20 articles satisfied the eligibility criteria. No studies of QoL in LDS, vEDS, or other HTAAD were found, only on MFS. Most studies had been published in the last 3 years. All were cross-sectional quantitative studies besides one pilot intervention study. Most studies were of small sample size, had low response rate or participants without verified diagnosis. Despite these limitations, most studies indicate that having an HTAAD diagnosis as MFS may negatively impact QoL, but few studies found any associations between the biomedical symptoms and decreased QoL. More research is needed on QoL in samples with verified HTAAD diagnosis to develop evidence-based knowledge and appropriate guidelines for these diagnoses.     

Familial aortic dissection in absence of ascending aortic aneurysms: a lethal syndrome associated with precocious systemic hypertension

The interaction of elevated blood pressure and aortic metabolism in the genesis of aortic dissection is uncharacterized. A kindred with fatal familial aortic dissection in association with precocious systemic hypertension and in absence of a definable connective tissue syndrome has undergone genealogical, clinical, pathological, and biochemical evaluation. Six family members spanning three generations have died of acute dissection. Five men died at a mean age of 28 years (range 22-34), while the proband's paternal grandmother died at 62 years of age. All were hypertensive. A constellation of subtle clinical features points toward deficient integrity of connective tissues; however, major hallmarks of known connective tissue syndromes including aortic root ectasia or aneurysms are absent. Studies of cultured dermal and aortae fibroblasts of two of the proband's brothers mitigate against Ehlers-Danlos IV syndrome. This family's susceptibility to aortic dissection reflects the synergistic liability of coexistent elevated blood pressure and metabolic abnormalities in the genesis of aortic degeneration.     

Transesophageal echocardiography guided patent ductus arteriosus occlusion in adults with severe pulmonary hypertension through a parasternal approach

Between April 2010 and April 2014, 39 consective adult patients (> 18 years) with PDA associated severe pulmonary hypertension underwent transesophageal echocardiography guided patent ductus arteriosus occlusion through a parasternal minimally invasive approach. Among 39 patients, the procedure was successful in 32 cases (82.1%) and failed in 7 cases (17.9%). In the failed cases, 3 cases had a large residual shunt and 4 cases had persistent pulmonary hypertension. The mean minimum miameter of the successfully closed PDAs was 15.2 ± 2.1 mm (range 9 to 24), and the mean diameter of the mushroom-shaped occluder was 17.5 ± 2.5 mm (range 11 to 26). The pulmonary artery pressure decreased significantly after occlusion (P < 0.05), but there were no significant differences in the aortic pressure and blood oxygen saturation before and after occlusion (P > 0.05). Echocardiography performed on the first postoperative day showed decreased volume within the left atrium, left ventricle, and pulmonary artery in 23 cases, decreased volume within the left atrium and left ventricle in 4 cases, and no change in the volume of the atrium and ventricle in 3 cases. A minor residual shunt was observed in 6 cases. The posteroanterior chest X-ray showed improved pulmonary congestion in all cases and significantly reduced cardiothoracic ratio in 25 cases. Patients were followed-up at least for 1 year. No symptoms including palpitation, dyspnoea, or chest tightness were observed. The heart function ranged from NYHA class I to II. A minor residual shunt was observed only in one case. There were varying degrees of decrease in volume within the atrium and ventricle. In conclusion, transesophageal echocardiography guided patent ductus arteriosus occlusion through a parasternal minimally invasive approach is a feasible and effective method for the treatment of PDA in adults with severe pulmonary hypertension.     

Case report of a 26 year old primigravida with patent ductus arteriosus (PDA) in heart failure

Congenital heart disease is an important cause of maternal morbidity and mortality during pregnancy. Pregnancy alters the circulatory and respiratory physiology with attendant deleterious effect on the mother with congenital heart disease and the foetus. Additional insult to the circulatory physiology by other factors coexisting together with congenital heart disease can further reduce the cardiac reserve in pregnancy and precipitate heart failure. These factors include anaemia, thromboembolism, hypertension, multiple pregnancy, strenuous physical activity, extremes of temperature and the normal physiological edema of pregnancy.Patent ductus arteriosus (PDA) can present for the first time in pregnancy. Moderate to large PDA result in significant volume overload, left ventricular dilation and dysfunction. In the woman with a hemodynamically important PDA, pregnancy may precipitate or worsen heart failure. We report a successful pregnancy in a 26 year old primigravida with previously undetected patent ductus arteriosus with preeclampsia who presented in heart failure. This case highlights the importance of intensive careful examination of pregnant patients to identify such conditions.