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Incontinence and psychological symptoms in individuals with Mowat-Wilson Syndrome.

Res Dev Disabil. 2017 Mar;62:230-237

Authors: Niemczyk J, Einfeld S, Mowat D, Equit M, Wagner C, Curfs L, von Gontard A

BACKGROUND: Mowat-Wilson Syndrome (MWS) is caused by deletion/mutation of the ZEB2 gene on chromosome 2q22. MWS is characterized by a distinctive facial appearance, severe intellectual disability and other anomalies, e.g. seizures and/or Hirschsprung disease (HSCR). Most individuals have a sociable demeanor, but one third show psychological problems.
AIMS: The aim was to investigate incontinence and psychological problems in MWS.
METHODS AND PROCEDURES: 26 children (4-12 years), 13 teens (13-17 years) and 8 adults (>18years) were recruited through a MWS support group. The Parental Questionnaire: Enuresis/Urinary Incontinence, as well as the Developmental Behaviour Checklist (DBC) were completed by parents or care-givers.
OUTCOMES AND RESULTS: 97.7% of persons with MWS had incontinence (nocturnal enuresis 74.4%; daytime urinary incontinence 76.2%; fecal incontinence 81.4%). Incontinence remained high over age groups (children 95.8%, teens 100%, adults 100%). 46.2% of children, 25% of teens and 37.5% of adults exceeded the clinical cut-off on the DBC. The ability to use the toilet for micturition improved with age.
CONCLUSIONS AND IMPLICATIONS: MWS incontinence rates are very high. All had physical disabilities including anomalies of the genitourinary and gastrointestinal tract. Due to the high prevalence rates, a screening for incontinence and psychological problems in MWS is recommended.

PMID: 28094084 [PubMed - indexed for MEDLINE]

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Original Findings and Updated Meta-Analysis for the Association Between Maternal Diabetes and Risk for Congenital Heart Disease Phenotypes.

Am J Epidemiol. 2017 Jul 01;186(1):118-128

Authors: Hoang TT, Marengo LK, Mitchell LE, Canfield MA, Agopian AJ

Maternal diabetes is associated with congenital heart defects (CHDs) as a group, but few studies have assessed risk for specific CHD phenotypes. We analyzed these relationships using data from the Texas Birth Defects Registry and statewide vital records for deliveries taking place in 1999-2009 (n = 48,249 cases). We used Poisson regression to calculate prevalence ratios for the associations between maternal diabetes (pregestational or gestational) and each CHD phenotype, adjusting for potential confounders. Analyses were repeated by type of diabetes. To address the potential for misclassification bias, we performed logistic regression, using malformed controls. We also conducted meta-analyses, combining our estimates of the association between pregestational diabetes and each CHD phenotype with previous estimates. The prevalence of every CHD phenotype was greater among women with pregestational diabetes than among nondiabetic women. Most of these differences were statistically significant (adjusted prevalence ratios = 2.47-13.20). Associations were slightly attenuated for many CHD phenotypes among women with gestational diabetes. The observed associations did not appear to be the result of misclassification bias. In our meta-analysis, pregestational diabetes was significantly associated with each CHD phenotype. These findings contribute to a better understanding of the teratogenic effects of maternal diabetes and improved counseling for risk of specific CHD phenotypes.

PMID: 28505225 [PubMed - indexed for MEDLINE]

Prognostic Value of Pulmonary Artery Compliance in Patients with Pulmonary Arterial Hypertension Associated with Adult Congenital Heart Disease.

Int Heart J. 2017 Sep 30;:

Authors: Cheng XL, Liu ZH, Gu Q, Ni XH, Luo Q, Zhao ZH, He JG, Xiong CM

In congenital heart disease (CHD), the presence of pulmonary arterial hypertension (PAH) is associated with a poor prognosis. In this study, we aim to investigate the role of pulmonary artery compliance (Cp) in predicting the mortality of PAH associated with adult congenital heart disease (APAH-CHD). One-hundred and seventy-five patients ofAPAH-CHD who underwent a comprehensive clinical evaluation were included in this study. All patients were followed up in a 6-month interval and the primary end point was all cause of death.The duration of mean follow-up was 67±26 months, of which there were twenty-three death. Cp had an inverse correlation with pulmonary artery resistance (PVR), regardless of the clinical phenotype (Eisenmenger syndrome, PAH with small defect and PAH after defect correction). Patients in the lowest Cp group (Cp ≤ 0.84 mL/mmHg) had advanced WHO function class, worse exercise tolerance, liver function, and status of oxygen saturation. In univariate cox regression analysis, Cp (HR = 1.359, P < 0.001), PVR (HR = 0.972, P = 0.001), pulmonary blood flow (HR = 1.092, P = 0.001), heart rate (HR = 1.038, P = 0.028) and 6-minute walking distance (HR = 1.003, P = 0.037) were predictors of survival. After adjustment by bivariate analysis, Cp was the independent predictor. Kaplan-Meier survival curves showed that patients with Cp < 1.04 mL/mmHg had worse prognosis. In conclusion, Cp possibly reflects disease severity and decreased Cp was associated with poor prognosis in patients with APAH-CHD.

PMID: 28966315 [PubMed - as supplied by publisher]

[22q11.2 microdeletion syndrome: Analysis of the care pathway before the genetic diagnosis].

Arch Pediatr. 2017 Sep 26;:

Authors: Ingrao T, Lambert L, Valduga M, Bosser G, Albuisson E, Leheup B

BACKGROUND: 22q11.2 deletion syndrome (22q11.2DS) is a very broad phenotypic spectrum disorder. It can affect many organs or systems. 22q11.2DS is the most common microdeletion syndrome in humans, with a prevalence ranging from one in every 2000 to one in 4000 newborns. It seems to be more prevalent than reported and under-recognized or undiagnosed because of its inherent clinical variability and heterogeneity. In France, 15,000 patients may be affected by this disease, more than half without knowing it. The aim of this study was to analyze the care pathway before the genetic diagnosis of 22q11.2DS.
METHODS: We conducted a single-center, retrospective analysis of postnatally diagnosed patients recruited by the cytogenetic laboratory of Nancy (France) from January 2000 to December 2015. Clinical data were first collected by consulting the medical files of patients and then by calling them directly. Written informed consent was obtained and the study was approved by local research ethics boards. Data concerned only clinical features before the diagnosis.
RESULTS: The cohort consisted of 32 individuals with 22q11.2DS. The average age at diagnosis was 9 years and 2 months and the median age was 2 years and 11 months. Fetal echography was abnormal in 15 pregnancies. During the neonatal period, the most important features were eating difficulties and congenital malformations (n=20), with a majority of complex heart diseases (n=16), dominated by conotruncal malformations (n=6). In case of malformation, the average age at diagnosis decreased to 2 years and 6 months. A congenital heart disease brought the average age of diagnosis down to 2 years and 6 months. Hypocalcemia and dysmorphism were also classical features (n=14). Before the age of 3 years, speech delay occurred in nine patients. After 3 years of age, rhinolalia was predominant (n=11). Academic disabilities were present in all subjects. At least 14 patients had a de novo deletion. Five patients were diagnosed within genetic counseling, with the deletion was inherited from the mother in three out of four cases. One was the monozygotic twin of a patient. Seven patients were diagnosed as adults. Four of them were diagnosed only because of the clinical presentation of their children or fetuses. Retrospectively, all adult patients had clinical signs suggesting the 22q11.2DS diagnosis. Relational disorders affected eight patients. None of them had been referred to the geneticist for this reason. In most cases, the pediatric cardiologist referred patients to the geneticist (n=9). Physiotherapists (n=15) and speech-language pathologists (n=12) were frequently requested but did not participate in the diagnosis.
CONCLUSION: The present study highlights the difficulty of establishing the diagnosis when the major features of the 22q11.2DS are absent during the 1st months of life. This is particularly true when there is no congenital defect. Special attention must be given to speech disorders in childhood and neuropsychological disorders later in life. The association between 22q11.2DS and early-onset parkinson disease implies that adult neurologists should be aware of this diagnosis. For adult patients, familial occurrence is the most frequent cause of diagnosis in spite of clinical signs suggestive of 22q11.2DS. The management of these patients involves better information of medical and paramedical staff in order to refer them to the geneticist earlier in life.

PMID: 28967605 [PubMed - as supplied by publisher]

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Association between levels of anti-angiogenic isoform of vascular endothelial growth factor A and pulmonary hypertension.

Int J Cardiol. 2016 Nov 01;222:416-20

Authors: Suzuki S, Yoshihisa A, Yokokawa T, Misaka T, Sakamoto N, Sugimoto K, Yamaki T, Kunii H, Nakazato K, Saitoh S, Takeishi Y

BACKGROUNDS: Pulmonary hypertension (PH) is characterized by elevated pulmonary arterial pressure due to vasoconstriction and remodeling of the pulmonary microvasculature. Vascular endothelial growth factor (VEGF) is a key contributor for angiogenesis and vasculogenesis. VEGF165b is recently identified as an anti-angiogenic splicing variant of VEGF. The aim of this study was to examine the association between circulating levels of VEGF165b in PH patients under consideration with classifications of PH.
METHODS AND RESULTS: We measured plasma levels of VEGF165b in the PH group (pulmonary artery hypertension [PAH], n=26; chronic thromboembolic pulmonary hypertension [CTEPH], n=13) and control group (n=30). Circulating levels of VEGF165b were higher in PH group than controls (97.1 vs. 53.3pg/ml, P<0.01). The multiple regression analysis demonstrated that the independent factor to determine the plasma levels of VEGF165b was the presence of PH (P=0.04). Next, we focused on differences in VEGF165b levels and classifications of PH. Plasma VEGF165b level was higher only in idiopathic PAH (n=9) than in control (137.1 vs. 53.3pg/ml, P<0.01), but not in PH related to collagen disease (n=7), congenital heart disease (n=10) and CTEPH (n=13).
CONCLUSIONS: We demonstrated associations between circulating levels of VEGF165b and classifications of PH. VEGF165b, anti-angiogenic isoform, might contribute to the pathophysiology in PH, especially in idiopathic PAH. The level of plasma VEGF165b might be a novel marker that reflects the pathological conditions in patients with PH.

PMID: 27505326 [PubMed - indexed for MEDLINE]

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Role of right ventricular three-dimensional electroanatomic voltage mapping for arrhythmic risk stratification of patients with corrected tetralogy of Fallot or other congenital heart disease involving the right ventricular outflow tract.

Int J Cardiol. 2016 Nov 01;222:422-9

Authors: Drago F, Pazzano V, Di Mambro C, Russo MS, Palmieri R, Silvetti MS, Giannico S, Leonardi B, Amodeo A, Di Ciommo VM

BACKGROUND: The post-surgical history of repaired congenital heart disease (rCHD), in particular tetralogy of Fallot (TOF), is often complicated by sudden death. Electrical myocardial abnormalities could be a substrate for malignant ventricular arrhythmias.
METHODS AND RESULTS: 146 patients with TOF or other rCHD involving a subpulmonary right ventricle, considered to be at high arrhythmic risk, underwent right ventricular (RV) electroanatomic voltage mapping (EVM). Maps showed endocardial scars (<0.5mV) in all cases, mainly involving the RV outflow tract (n=141, 96.6%). In 28 cases (19.2%), other areas were involved. Total scar extension, expressed as % of total endocardial area, was significantly higher in patients with QRS ≥180ms [4.5% (±2.5) vs 2.8% (±2.4), p=0.014], left and right ventricular systolic dysfunction [4.5% (±3.2) vs 2.8% (±2.3), p=0.016 and 3.5% (±3.0) vs 2.6% (±1.9), p=0.03, respectively], premature ventricular contractions (PVCs) [3.2% (±2.6) vs 2.2% (±1.8), p<0.05], exercise-induced PVCs [3.8% (±2.4) vs 2.6% (±2.2), p=0.01], previous shunt [4.0% (±2.7) vs 2.6% (±2.2), p=0.01] and reintervention [4.2% (±3.2) vs 2.6% (±2.0), p=0.008]. Scar size also showed a positive correlation with duration of post-surgical follow-up (ρ=0.01), age at correction (ρ=0.01) and absolute QRS duration (ρ=0.05).
CONCLUSIONS: Patients with rCHD involving the right ventricle show electrical scars with variable distribution, not necessarily matching with sites of surgical lesions. Scar extension correlates with some of the risk factors for life-threatening arrhythmias in CHD, such as prolonged QRS. Thus EVM could be considered an additional tool in the assessment of risk stratification in this particular population.

PMID: 27505328 [PubMed - indexed for MEDLINE]

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Optical coherence tomography for hypertensive pulmonary vasculature.

Int J Cardiol. 2016 Nov 01;222:494-8

Authors: Jiang X, Peng FH, Liu QQ, Zhao QH, He J, Jiang R, Wang L, Xu XQ, Li JH, Ebrahimi R, Jing ZC

BACKGROUND: Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing in situ images of tissues at near histologic resolution. In this study we examine the utility of OCT in identifying vascular changes related to pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).
METHODS AND RESULTS: OCT of four different distal pulmonary arteries was performed during right heart catheterization in 87 patients, 64 patients with PAH and 23 patients with CTEPH. The mean luminal diameter measured by OCT for all patients was 2.26mm. Intimal thickening was significantly increased in all PAH patients (0.26±0.05mm in idiopathic PAH, 0.24±0.03mm in connective tissue disease related PAH, 0.26±0.06mm in congenital heart disease related PAH and 0.22±0.04mm in CTEPH, respectively) compared with controls (0.13±0.03mm) (all p<0.05). An intimal thickness of ≥0.176mm had a 91% positive predictive value for pulmonary hypertension. The anatomic abnormalities revealed by OCT tended to be severe in the idiopathic PAH group and mild in the CTEPH group. Signs of intravascular webs were found in 60.9% of CTEPH patients, but no other patients. Intimal thickness was moderately correlated with pulmonary arterial pressure and pulmonary vascular resistance (r=0.423 and 0.439, respectively, p<0.001).
CONCLUSIONS: OCT provides important information for assessment of pulmonary arterial remodeling in patients with PAH and improves diagnostic capability of angiographically undetected distal-thrombotic lesions in patients with CTEPH.

PMID: 27505340 [PubMed - indexed for MEDLINE]

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Functional Mitral Regurgitation Predicts Short-Term Adverse Events in Patients With Acute Heart Failure and Reduced Left Ventricular Ejection Fraction.

Am J Cardiol. 2017 Oct 15;120(8):1344-1348

Authors: De la Espriella R, Santas E, Miñana G, Bodí V, Valero E, Payá R, Núñez E, Payá A, Chorro FJ, Bayés-Genis A, Sanchis J, Núñez J

Functional mitral regurgitation (FMR) is a common finding in patients with acute heart failure (AHF) and reduced left ventricular ejection fraction (heart failure and reduced ejection fraction [HFrEF]). However, its clinical impact remains unclear. We aimed to evaluate the association between the severity of FMR after clinical stabilization and short-term adverse outcomes after a hospitalization for AHF. We prospectively included 938 consecutive patients with HFrEF discharged after a hospitalization for AHF, after excluding those with organic valve disease, congenital heart disease, or aortic valve disease. FMR was assessed semiquantitatively by color Doppler analysis of the regurgitant jet area, and its severity was categorized as none or mild (grade 0 or 1), moderate (grade 2), or severe (grade 3 or 4). FMR was assessed at 120 ± 24 hours after admission. The primary end point was the composite of all-cause mortality and rehospitalization at 90 days. At discharge, 533 (56.8%), 253 (26.9%), and 152 (16.2%) patients showed none-mild, moderate, and severe FMR. At the 90-day follow-up, 161 patients (17.2%) either died (n = 49) or were readmitted (n = 112). Compared with patients with none or mild FMR, rates of the composite end point were higher for patients with moderate and severe FMRs (p <0.001). After the multivariable adjustment, those with moderate and severe FMRs had a significantly higher risk of reaching the end point (hazard ratio = 1.50, 95% confidence interval 1.04 to 2.17, p = 0.027; and hazard ratio = 1.63, 95% confidence interval 1.07 to 2.48, p = 0.023, respectively). In conclusion, FMR is a common finding in patients with HFrEF, and its presence, when moderate or severe, identifies a subgroup at higher risk of adverse clinical outcomes at short term.

PMID: 28823484 [PubMed - indexed for MEDLINE]

A novel method for evaluating regional RV function in the adult congenital heart with low-dose CT and SQUEEZ processing.

Int J Cardiol. 2017 Sep 29;:

Authors: Contijoch FJ, Groves DW, Chen Z, Chen MY, McVeigh ER

BACKGROUND: Measuring local RV function in adult congenital heart disease (ACHD) with echocardiography or MRI is challenging because of the complex geometry and existing pacing devices. Visual assessment of ventricular function via low-dose cardiac CT has been recently performed. This pilot study assessed whether low-dose 4D cine CT combined with automatic measurement of regional shortening could quantify right-ventricular function in ACHD patients.
METHODS: Seven patients with Tetralogy of Fallot either contraindicated for MRI or assessed for coronary artery disease and seven non-congenital patients were imaged with ECG-gated cardiac CT utilizing a 320-detector row scanner. Right ventricular global function and regional shortening were quantified.
RESULTS: Non-congenital patients were imaged with 2.9±2.1mSv and 395±359 HU blood-myocardium contrast. The ACHD patients were imaged with 2.1±1.3mSv and 726±296 HU contrast. Right ventricles of the ACHD patients had higher end-diastolic volume (297±107mL vs 123±34mL, p=0.001), lower ejection fraction (32.0±4.9% vs 45.0±6.0%, p=0.001), and higher dyskinetic fraction (10.9±3.7% vs 2.6±2.8%, p<0.001) relative to the non-congenital controls.
CONCLUSIONS: In this initial pilot study, right ventricular global and regional systolic function were measured using low-dose cine CT with SQUEEZ quantification in non-congenital patients as well as ACHD patients with Tetralogy of Fallot. Unique regional features of RV dyskinesia were identified in the ACHD patients which could yield a more precise quantification of RV function.

PMID: 28970037 [PubMed - as supplied by publisher]

Histopathological abnormalities in the central arteries and veins of Fontan subjects.

Heart. 2017 Sep 29;:

Authors: Hays BS, Baker M, Laib A, Tan W, Udholm S, Goldstein BH, Sanders SP, Opotowsky AR, Veldtman GR

OBJECTIVE: Fontan circulations have obligatory venous hypertension, depressed cardiac output and abnormal arterial elastance. Ventriculovascular coupling is known to be abnormal, but the underlying mechanisms are poorly defined. We aim to describe the histopathological features of vascular remodelling encountered in the central arteries and veins in the Fontan circulation as a possible underlying pathological representation of abnormal ventriculovascular coupling.
METHODS: Postmortem vasculature (inferior vena cava (IVC), superior vena cava (SVC), pulmonary artery (PA), pulmonary vein (PV) and aorta) of 13 patients with a Fontan circulation (mean age 29.9 years, range 9.0-59.8 years) and 2 biventricular controls (ages 17.9 and 30.2 years) was examined.
RESULTS: IVC and SVC: Eccentric and variable intimal fibromuscular proliferation occurred in 11 Fontan subjects. There was variable loss of medial smooth muscle bundles with reciprocal replacement with dense collagenous tissue.PA: Similar intimal fibromuscular proliferation was seen; however, these intimal changes were accompanied by medial thinning rather than expansion, medial myxoid degeneration and elastic alteration.PV: The PVs demonstrated intimal fibroproliferation and disorganisation of the muscular media.Aorta: The aortic lamina intima was thickened, with associated fibromuscular proliferation and elasticisation. There was also moderate lymphocytic inflammation in the aortic wall.
CONCLUSIONS: Vascular architectural remodelling is common in Fontan patients. The central veins demonstrate profound changes of eccentric intimal expansion and smooth muscle replacement with collagen. The pulmonary demonstrated abnormal intimal proliferation, and aortic remodelling was characterised by intima lamina thickening and a moderate degree of aortic wall inflammation.

PMID: 28970278 [PubMed - as supplied by publisher]