Congenital Heart Disease and Pulmonary Hypertension

Gupta, Vedant; Tonelli, Adriano R.; Krasuski, Richard A.

doi:10.1016/j.hfc.2012.04.002

Cited by 10 publications

(8 citation statements)

References 167 publications

(211 reference statements)

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“…Various cardiovascular developmental abnormalities, such as ventricular septal defect, atrial septal defect, tetralogy of Fallot, patent ductus arteriosis, atrioventricular septal defect, double outlet right ventricle, pulmonary stenosis, and transposition of great arteries, may occur individually or in combination. These anomalies may result in degraded quality of life, delayed fetal brain development, cardiac enlargement or hypertrophy, pulmonary hypertension, infective endocarditis, thromboembolism, Eisenmenger's syndrome, congestive heart failure, arrhythmias, as well as sudden cardiac death in the absence of surgical or catheter-based repairs (4)(5)(6)(7)(8)(9)(10). Despite the high prevalence and significant clinical importance, the molecular mechanism of CHD remains poorly understood (11).…”

Section: Introductionmentioning

confidence: 99%

Somatic GATA5 mutations in sporadic tetralogy of Fallot

Huang

Xue

et al. 2014

International Journal of Molecular Medicine

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Abstract. Tetralogy of Fallot (TOF) is the most common form of cyanotic congenital heart disease, with high morbidity and mortality rates. Accumulating evidence has demonstrated that genetic defects play an important role in the pathogenesis of TOF. However, the molecular basis of TOF in the majority of patients remains to be determined. In the present study, sequence analysis of the coding exons and exon-intron boundaries of GATA5, a gene encoding a zinc finger-containing transcriptional factor crucial for cardiogenesis, was performed on genomic DNA isolated from resected cardiac tissue and matched blood samples of 85 unrelated patients who underwent surgical repair of TOF. Genotyping was performed on the cardiac tissue and matched blood samples from 63 unrelated patients who underwent cardiac valve replacement due to rheumatic heart disease as well as the blood samples obtained from 200 unrelated healthy individuals. The functional effect of the mutations was evaluated by using a luciferase reporter assay system. As a result, the novel heterozygous GATA5 mutations, p.D203E and p.Y208X, were found in the cardiac tissues of two TOF patients, respectively. There were no mutations in the cardiac tissues obtained from 63 patients with rheumatic heart disease nor in the blood samples obtained from the 348 subjects. Functional analysis revealed that the GATA5 mutants were consistently associated with significantly decreased transcriptional activity compared with their wild-type counterpart. Thus, results of this study showed an association of somatic GATA5 mutations with TOF, providing further insight into the underlying molecular mechanism of TOF.

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Section: Introductionmentioning

confidence: 99%

Somatic GATA5 mutations in sporadic tetralogy of Fallot

Huang

Xue

et al. 2014

International Journal of Molecular Medicine

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“…The clinical presentation of PH is nonspecific, and includes exertional dyspnea, fatigue, chest pain, and syncope [38]. ACHD patients with progressive PH often subconsciously decrease activity and may be unaware of their limitations.…”

Section: Pulmonary Hypertensionmentioning

confidence: 99%

“…Truncus arteriosus, ventricular septal defect, ASD, and patent ductus arteriosus are the most commonly identified lesions associated with severe PH and Eisenmenger syndrome [38]. As compared with atrial-level shunting, ventricular-level shunts cause volume and pressure overload and lead to earlier and more severe PH [36,37].…”

Section: Pulmonary Hypertensionmentioning

confidence: 99%

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Extra-cardiac manifestations of adult congenital heart disease

Gaeta

Ward

Krasuski

2016

Trends in Cardiovascular Medicine

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a b s t r a c tAdvancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations.Key words: Cardiovascular disease, Adult congenital heart disease, Pulmonary hypertension. Advances in the diagnosis and management of congenital heart disease (CHD) over the past several decades have greatly improved longevity and quality of life in the CHD population. Palliative or corrective interventions are now available for nearly every type of congenital cardiac lesion, and approximately 90% of affected children now survive to adulthood [1]. Adults with CHD (ACHD) already outnumber pediatric CHD patients, and this population is expected to grow by 5% per year [1,2]. Strikingly, the median age of severe CHD patients has increased from 11 years in 1985 to 25 years in 2010 [3]. Continued improvement in CHD interventions means that new (and more complex) populations will likely reach adulthood in the coming years.Practitioners who take care of adults with CHD are often charged with the delivery or coordination of comprehensive care for these complex patients, including the management of manifestations and complications that arise later in life. ACHD has many extra-cardiac effects, both as syndromic associations with congenital heart defects, or more commonly, as sequelae of primary structural or hemodynamic abnormalities. The role of genetic predilection remains undefined for nearly all extra-cardiac complications, though their incidence has clearly risen over the past decades. Indeed, more than a third of hospital admissions for ACHD patients are now for noncardiovascular reasons [4]. Optimal care of ACHD patients, therefore, mandates a thorough understanding of its multiorgan system manifestations. Herein, we will review current understanding of the most common manifestations of ACHD organized by the affected organ systems. Neurologic/neuropsychiatric Cerebrovascular complicationsA recent study quantified the strikingly high rates of stroke in ACHD [5]. Among nearly 30,000 ACHD patients, 8.9% of men http://dx

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“…Pulmonary hypertension (PH) is a fatal disease characterized by a progressive increase in pulmonary vascular resistance with remodeling of the pulmonary vasculature, which previously carried a poor prognosis in children with congenital heart disease (CHD) [6,12,25]. Endothelial dysfunction contributes to sustained pulmonary vasoconstriction and endothelial and vascular smooth muscle cell proliferation, playing a very important role in the complex pathology of PH [4,7].…”

Section: Introductionmentioning

confidence: 99%

Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension Associated with Congenital Heart Disease

Xia

Jia

et al. 2015

Pediatr Cardiol

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This study aims to estimate plasma levels of acylated ghrelin in children with pulmonary hypertension (PH) associated with congenital heart disease (CHD) and to correlate the levels of acylated ghrelin with endothelin-1 (ET-1), nitric oxide (NO), and clinical hemodynamic parameters. We investigated the plasma concentration of acylated ghrelin, ET-1, NO, and the hemodynamic parameters in 20 children with CHD, 20 children with PH-CHD, and 20 normal children. Plasma-acylated ghrelin and NO levels were significantly higher in CHD group than in control subjects (P < 0.001). Moreover, plasma-acylated ghrelin, ET-1, and NO levels were significantly elevated in PH-CHD group compared with the CHD group (P < 0.05). In PH-CHD children, plasma-acylated ghrelin levels correlated positively with pulmonary artery systolic pressure (PASP; r = 0.740, P < 0.001), pulmonary artery diastolic pressure (PADP; r = 0.613, P = 0.004), right ventricular systolic pressure (RVSP; r = 0.642, P = 0.002), mean pulmonary arterial hypertension (mPAP; r = 0.685, P = 0.001), right ventricle diameter (RVD; r = 0.473, P = 0.035), pulmonary artery trunk diameter (PAD; r = 0.613, P = 0.004), NO (r = 0.463, P = 0.04), and ET-1 (r = 0.524, P = 0.018). Plasma-acylated ghrelin levels were elevated both in CHD and in PH-CHD. Increased acylated ghrelin levels correlated positively with ET-1, NO, PASP, PADP, RVSP, mPAP, RVD, and PAD. Acylated ghrelin may be a new biomarker of PH-CHD.

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Congenital Heart Disease and Pulmonary Hypertension

Cited by 10 publications

References 167 publications

Somatic GATA5 mutations in sporadic tetralogy of Fallot

Somatic GATA5 mutations in sporadic tetralogy of Fallot

Extra-cardiac manifestations of adult congenital heart disease

Plasma Levels of Acylated Ghrelin in Children with Pulmonary Hypertension Associated with Congenital Heart Disease

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