Effect of age on exercise capacity and cardiac reserve in patients with pulmonary atresia with intact ventricular septum after biventricular repair

OBJECTIVESIn patients with pulmonary atresia with intact ventricular septum (PAIVS), biventricular repair is considered to be the optimal treatment option in the absence of significant right ventricular (RV) hypoplasia. However, long-term clinical outcome studies are limited. We evaluated exercise capacity and cardiac function during pharmacological stress in children and young adults with PAIVS after biventricular repair.METHODSTen PAIVS patients after biventricular repair, with a median age of 12 years (range 9-42 years), underwent a cardiopulmonary exercise test, dobutamine stress magnetic resonance imaging (DS-MRI) and delayed contrast enhancement (DCE) MRI.RESULTSThe patients' ages negatively correlated with exercise capacity (r = -0.72, P = 0.01) as well as left (LV) and RV stroke volume (SV) response to pharmacological stress (r = -0.72, P = 0.02; and r = -0.64, P = 0.04; respectively), Furthermore, older age was associated with decreased RV E/A volume ratio and increased pulmonary late diastolic forward flow percentage (r = 0-0.65, P = 0.04, r = 0.66, P = 0.03, respectively). RV E/A volume ratio positively correlated with RV-SV response to DS-MRI (r = 0.77, P = 0.009). and O(2)-pulse during physical stress correlated with biventricular SV response to DS-MRI. No RV or LV ventricular myocardial fibrosis was detected.CONCLUSIONSIn PAIVS patients after biventricular repair exercise capacity and cardiac reserve decrease with age. These findings appear to be related to impaired diastolic RV function and decreased RV filling, indicating that the function of the relatively small RV deteriorates with tim

Pulse-shape discrimination with PbWO4_4 crystal scintillators

The light output, $\alpha/\beta$ ratio, and pulse shape have been investigated at $-25^\circ$ C with PbWO$_4$ crystal scintillators undoped, and doped by F, Eu, Mo, Gd and S. The fast $0.01-0.06 \mu$s and middle $0.1-0.5 \mu$s components of scintillation decay were observed for all the samples. Slow components of scintillation signal with the decay times $1-3 \mu$s and $13-28 \mu$s with the total intensity up to $\approx50$ have been recognized for several samples doped by Molybdenum. We found some indications of a pulse-shape discrimination between $\alpha$ particles and $\gamma$ quanta with PbWO$_4$ (Mo doped) crystal scintillators.Comment: 12 pages, 5 figures, submitted to NIM

Advanced therapy for pulmonary arterial hypertension due to congenital heart disease: a clinical perspective in a new therapeutic era

Cardiolog

Lifelong CRF overproduction is associated with altered gene expression and sensitivity of discrete GABAA and mGlu receptor subtypes

RATIONALE: Repeated activation of corticotropin-releasing factor (CRF) receptors is associated with increased anxiety and enhanced stress responsivity, which may be mediated via limbic GABAergic and glutamatergic transmission. OBJECTIVE: The present study investigated molecular and functional alterations in GABA(A) receptor (GABA(A)R) and metabotropic glutamate receptor (mGluR) responsivity in transgenic mice that chronically overexpress CRF. METHODS: CRF(1) receptor, GABA(A)R, and mGluR sensitivity were determined in CRF-overexpressing mice using the stress-induced hyperthermia (SIH) test. In addition, we measured mRNA expression levels of GABA(A)R α subunits and mGluRs in the amygdala and hypothalamus. RESULTS: CRF-overexpressing mice were less sensitive to the anxiolytic effects of the CRF(1) receptor antagonists CP154,526 and DMP695, the GABA(A)R α(3)-selective agonist TP003 (0–3 mg/kg) and the mGluR(2/3) agonist LY379268 (0–10 mg/kg) in the SIH test. The hypothermic effect of the non-selective GABA(A)R agonist diazepam (0–4 mg/kg) and the α(1)-subunit-selective GABA(A)R agonist zolpidem (0–10 mg/kg) was reduced in CRF-overexpressing mice. No genotype differences were found using the GABA(A)R α(5)-subunit preferential compound SH-053-2′F-R-CH(3) and mGluR(5) antagonists MPEP and MTEP. CRF-overexpressing mice showed decreased expression levels of GABA(A)R α(2) subunit and mGluR(3) mRNA levels in the amygdala, whereas these expression levels were increased in the hypothalamus. CRF-overexpressing mice also showed increased hypothalamic mRNA levels of α(1) and α(5) GABA(A)R subunits. CONCLUSIONS: We found that lifelong CRF overproduction is associated with altered gene expression and reduced functional sensitivity of discrete GABA(A) and mGluR receptor subtypes. These findings suggest that sustained over-activation of cerebral CRF receptors may contribute to the development of altered stress-related behavior via modulation of GABAergic and glutamatergic transmission

European reference network for rare vascular diseases (VASCERN) consensus statement for the screening and management of patients with pathogenic ACTA2 variants

Malaltia aòrtica; Dissecció; Aneurisma aòrtic toràcicEnfermedad aórtica; Disección; Aneurisma de aorta torácicaAortic disease; Dissection; Thoracic aortic aneurysmThe ACTA2 gene encodes for smooth muscle specific α-actin, a critical component of the contractile apparatus of the vascular smooth muscle cell. Pathogenic variants in the ACTA2 gene are the most frequently encountered genetic cause of non-syndromic hereditary thoracic aortic disease (HTAD). Although thoracic aortic aneurysm and/or dissection is the main clinical manifestation, a variety of occlusive vascular disease and extravascular manifestations occur in ACTA2-related vasculopathy. Current data suggest possible mutation-specific manifestations of vascular and extra-aortic traits. Despite its relatively high prevalence, comprehensive recommendations on the care of patients and families with pathogenic variants in ACTA2 have not yet been established. We aimed to develop a consensus document to provide medical guidance for health care professionals involved in the diagnosis and treatment of patients and relatives with pathogenic variants in ACTA2. The HTAD Working Group of the European Reference Network for Rare Vascular Diseases (VASCERN) convened to review current literature and discuss expert opinions on clinical management of ACTA2 related vasculopathy. This consensus statement summarizes our recommendations on diagnosis, monitoring, treatment, pregnancy, genetic counselling and testing in patients with ACTA2-related vasculopathy. However, there is a clear need for additional prospective multicenter studies to further define proper guidelines.This work was supported by the Dutch Heart Foundation (2014 T007) and by an Erasmus University Rotterdam Fellowship (I.M.B.H. van de Laar)

Aortic distensibility in Marfan syndrome:a potential predictor of aortic events?

Contains fulltext : 239962.pdf (Publisher’s version ) (Open Access

Penetration of left and right atrial wall and aortic root by an Amplatzer atrial septal occluder in a nine year old boy with Marfan syndrome: Case report

<p>Abstract</p> <p>Background</p> <p>To describe complications associated with Amplatzer septal occluders in a patient with Marfan syndrome</p> <p>Case presentation</p> <p>A nine-year-old boy with Marfan syndrome and a 22 mm atrial septal defect (ASD) was treated successfully by interventional closure of his ASD by placing a 24 mm Amplatzer septal occluder. Follow up examinations showed a good result but an increasing enlargement of aortic root, so the patient was scheduled for operation. Intraoperative findings showed a perforation of the left atrial roof and the non-coronary sinus by penetration of the occluder device as well as penetration into the right atrial wall. The occluder was resected, the ASD was closed and the aortic sinus was reconstructed using a Dacron patch.</p> <p>Conclusion</p> <p>We describe the first case of a patient with Marfan syndrome and an interventional closure of an ASD. Due to alterations of the connective tissue, as it is typical for patients with Marfan syndrome, the Amplatzer occluder probably perforated adjacent structures more easily as in non-affected individuals. Amplatzer occluders should be used with caution and follow up examinations should be performed in short intervals.</p

Evaluating the systemic right ventricle by CMR: the importance of consistent and reproducible delineation of the cavity

Contains fulltext : 70334.pdf (publisher's version ) (Open Access)BACKGROUND: The method used to delineate the boundary of the right ventricle (RV), relative to the trabeculations and papillary muscles in cardiovascular magnetic resonance (CMR) ventricular volume analysis, may matter more when these structures are hypertrophied than in individuals with normal cardiovascular anatomy. This study aimed to compare two methods of cavity delineation in patients with systemic RV. METHODS: Twenty-nine patients (mean age 34.7 +/- 12.4 years) with a systemic RV (12 with congenitally corrected transposition of the great arteries (ccTGA) and 17 with atrially switched (TGA) underwent CMR. We compared measurements of systemic RV volumes and function using two analysis protocols. The RV trabeculations and papillary muscles were either included in the calculated blood volume, the boundary drawn immediately within the apparently compacted myocardial layer, or they were manually outlined and excluded. RV stroke volume (SV) calculated using each method was compared with corresponding left ventricular (LV) SV. Additionally, we compared the differences in analysis time, and in intra- and inter-observer variability between the two methods. Paired samples t-test was used to test for differences in volumes, function and analysis time between the two methods. Differences in intra- and inter-observer reproducibility were tested using an extension of the Bland-Altman method. RESULTS: The inclusion of trabeculations and papillary muscles in the ventricular volume resulted in higher values for systemic RV end diastolic volume (mean difference 28.7 +/- 10.6 ml, p < 0.001) and for end systolic volume (mean difference 31.0 +/- 11.5 ml, p < 0.001). Values for ejection fraction were significantly lower (mean difference -7.4 +/- 3.9%, p < 0.001) if structures were included. LV SV did not differ significantly from RV SV for both analysis methods (p = NS). Including structures resulted in shorter analysis time (p < 0.001), and showed better inter-observer reproducibility for ejection fraction (p < 0.01). CONCLUSION: The choice of method for systemic RV cavity delineation significantly affected volume measurements, given the CMR acquisition and analysis systems used. We recommend delineation outside the trabeculations for routine clinical measurements of systemic RV volumes as this approach took less time and gave more reproducible measurements

Genome-wide methylation patterns in Marfan syndrome

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