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Transseptal puncture using surgical electrocautery in children and adults with and without complex congenital heart disease.

Catheter Cardiovasc Interv. 2017 Sep 01;90(3):E46-E54

Authors: Gowda ST, Qureshi AM, Turner D, Madan N, Weigand J, Lorber R, Singh HR

Abstract
BACKGROUND: Atrial transseptal puncture (TSP) for cardiac catheterization procedures remain challenging in children and adults with complex congenital heart disease (CHD).
OBJECTIVES: We sought to evaluate our experience using radiofrequency (RF) current via surgical electrocautery needle for TSP to facilitate diagnostic and interventional procedures.
METHODS: Retrospective chart review of all patients (pts) who underwent TSP using RF energy (10-25 W) via surgical electrocautery from three centers from January 2011 to January 2017 were evaluated. Echocardiograms were reviewed to define the atrial septum as normal and complex (thin aneurysmal, thick/fibrotic, synthetic patch material, and extra cardiac conduit).
RESULTS: A total of 54 pts underwent 55 successful TSP. Median age was 12.5 years (1 day-54 years) and weight was 52.7 kg (2-162). Indications for TSP included; EP study and ablation procedures in structurally normal hearts (n = 24) and in complex atrial septum/CHD and structural heart disease pts (n = 30): Electrophysiology study and ablation in 4, diagnostic catheterization in 9, and interventional procedures in 17 pts were performed. Atrial TSP was successful in 54/55 (98%). Atrial perforation with tiny-small pericardial effusion not requiring intervention was noted in 2 pts. TSP was unsuccessful in one critically ill neonate with unobstructed TAPVR and restricted atrial septum who experienced cardiac arrest requiring CPR, ECMO, and emergent surgery.
CONCLUSIONS: RF current delivery using surgical electrocautery for TSP is a feasible and an effective option in patients with complex CHD for diagnostic, interventional, and electrophysiology procedures.

PMID: 28766834 [PubMed - indexed for MEDLINE]

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Acute and Midterm Outcomes of Transcatheter Pulmonary Valve Replacement for Treatment of Dysfunctional Left Ventricular Outflow Tract Conduits in Patients With Aortopulmonary Transposition and a Systemic Right Ventricle.

Circ Cardiovasc Interv. 2017 Sep;10(9):

Authors: Whiteside W, Tretter JT, Aboulhosn J, Aldoss O, Armstrong AK, Bocks ML, Gillespie MJ, Jones TK, Martin MH, Meadows JJ, Metcalf CM, Turner ME, Zellers T, Goldstein BH

Abstract
BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) is an established therapy for dysfunctional right ventricular (RV) outflow tract conduits. TPVR in patients with congenitally corrected transposition of the great arteries, subpulmonary left ventricle, and left ventricular outflow tract (LVOT) conduit dysfunction has not been studied. Unique anatomic and physiological aspects of this population may contribute to distinct risks and outcomes.
METHODS AND RESULTS: Across 10 US centers, 27 patients with a dysfunctional LVOT conduit were evaluated in the catheterization laboratory between December 2008 and August 2015 with the intent to perform TPVR. TPVR was successful in 23 patients (85%). Five serious adverse events occurred in 4 cases (15%), including pulmonary hemorrhage, hypotension requiring vasoactive support, conduit disruption requiring covered stent (n=2), and acute RV dysfunction with flash pulmonary edema. After TPVR, the LVOT peak systolic ejection gradient decreased from median of 35 to 17 mm Hg (P<0.001); pulmonary insufficiency was trivial/none in all but 1 patient, where it was mild. Worsening of systemic RV dysfunction or tricuspid regurgitation was seen in 12 patients (57%) and was associated with a significantly lower post-TPVR LVOT peak systolic ejection gradient (median 17 versus 21 mm Hg; P=0.02) and higher post-TPVR RV sphericity index (median 0.88 versus 0.52; P=0.004). Post-TPVR, there were 2 late deaths because of RV failure and 1 cardiac transplantation because of progressive RV dysfunction and tricuspid regurgitation.
CONCLUSIONS: TPVR in dysfunctional LVOT conduits is feasible but associated with an important rate of TPV nonimplantation and procedural serious adverse events. Worsening systemic RV function and tricuspid regurgitation may develop after LVOT TPVR.

PMID: 28851718 [PubMed - indexed for MEDLINE]

Related Articles

Identification of a mutation in CNNM4 by whole exome sequencing in an Amish family and functional link between CNNM4 and IQCB1.

Mol Genet Genomics. 2018 Jun;293(3):699-710

Authors: Li S, Xi Q, Zhang X, Yu D, Li L, Jiang Z, Chen Q, Wang QK, Traboulsi EI

Abstract
We investigated an Amish family in which three siblings presented with an early-onset childhood retinal dystrophy inherited in an autosomal recessive fashion. Genome-wide linkage analysis identified significant linkage to marker D2S2216 on 2q11 with a two-point LOD score of 1.95 and a multi-point LOD score of 3.76. Whole exome sequencing was then performed for the three affected individuals and identified a homozygous nonsense mutation (c.C1813T, p.R605X) in the cyclin and CBS domain divalent metal cation transport mediator 4 (CNNM4) gene located within the 2p14-2q14 Jalili syndrome locus. The initial assessment and collection of the family were performed before the clinical delineation of Jalili syndrome. Another assessment was made after the discovery of the responsible gene and the dental abnormalities characteristic of Jalili syndrome were retrospectively identified. The p.R605X mutation represents the first probable founder mutation of Jalili syndrome identified in the Amish community. The molecular mechanism underlying Jalili syndrome is unknown. Here we show that CNNM4 interacts with IQCB1, which causes Leber congenital amaurosis (LCA) when mutated. A truncated CNNM4 protein starting at R605 significantly increased the rate of apoptosis, and significantly increased the interaction between CNNM4 and IQCB1. Mutation p.R605X may cause Jalili syndrome by a nonsense-mediated decay mechanism, affecting the function of IQCB1 and apoptosis, or both. Our data, for the first time, functionally link Jalili syndrome gene CNNM4 to LCA gene IQCB1, providing important insights into the molecular pathogenic mechanism of retinal dystrophy in Jalili syndrome.

PMID: 29322253 [PubMed - indexed for MEDLINE]

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

Book. 2016

Authors: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H

Abstract
The neonatal mammalian heart is capable of substantial regeneration following injury through cardiomyocyte proliferation (Porrello et al, Science 331:1078–1080, 2011; Proc Natl Acad Sci U S A 110:187–92, 2013). However, this regenerative capacity is lost by postnatal day 7 and the mechanisms of cardiomyocyte cell cycle arrest remain unclear. The homeodomain transcription factor Meis1 is required for normal cardiac development but its role in cardiomyocytes is unknown (Paige et al, Cell 151:221–232, 2012; Wamstad et al, Cell 151: 206–220, 2012). Here we identify Meis1 as a critical regulator of the cardiomyocyte cell cycle. Meis1 deletion in mouse cardiomyocytes was sufficient for extension of the postnatal proliferative window of cardiomyocytes and for reactivation of cardiomyocyte mitosis in the adult heart with no deleterious effect on cardiac function. In contrast, overexpression of Meis1 in cardiomyocytes decreased neonatal myocyte proliferation and inhibited neonatal heart regeneration. Finally, we show that Meis1 is required for transcriptional activation of the synergistic CDK inhibitors p15, p16, and p21. These results identify Meis1 as a critical transcriptional regulator of cardiomyocyte proliferation and a potential therapeutic target for heart regeneration.


PMID: 29787104

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

Book. 2016

Authors: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H

Abstract
Heterotaxy syndrome is characterized by a wide variety of cardiac and extra-cardiac congenital malformations that are primarily induced by disorders of the left-right axis determination during early embryonic development. Prognosis of the disease remains unsatisfactory because the syndrome is often associated with complicated congenital heart diseases. Long-term follow-up of heterotaxy patients, particularly those who underwent Fontan procedure, is now one of the most important issues in pediatric and adult congenital heart disease clinics. Collaborative studies between pediatric cardiologists and basic scientists are essential for improving the prognosis of heterotaxy syndrome.


PMID: 29787107

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

Book. 2016

Authors: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H

Abstract
The adult mammalian heart is incapable of regeneration after injury, as shown by the limited amount of cardiomyocyte proliferation and poor neovascularization. We recently showed that neonatal mice have a remarkable ability to regenerate damaged heart after apical resection or myocardial infarction (MI), which includes complete reconstruction of myocardial wall with vascular network [2, 3]. Although lineage tracing showed that the main source of newly formed cardiomyocyte is preexisting cardiomyocytes, it is still possible that there is a minor contribution of other types of cells to the cardiomyocyte. In addition, lineage origin of the newly formed vasculature during postnatal cardiac maturation and neonatal heart regeneration remains unclear (Fig. 50.1).


PMID: 29787132

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

Book. 2016

Authors: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H

Abstract
Polycomb-group (PcG) proteins maintain transcriptional silencing through specific histone modification and are essential for cell-fate transition and proper development of embryonic and adult stem cells. Recent advances in molecular analysis of PcG proteins have revealed that the distinct subunit composition of PRC1 confers specific and nonoverlapping functions for regulation of embryonic and adult stem cells. Here, we provide an overview of recent findings regarding the role of PcG proteins in cardiac development, with focus on the diversity of PcG complexes.


PMID: 29787140

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

Book. 2016

Authors: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H

Abstract
Bicuspid aortic valve (BAV) is the most common type of cardiac malformation with an estimated prevalence of 1 % in the population. BAV results in significant morbidity usually during adulthood due to its association with aortic valve calcification and ascending aortic aneurysms. Mutations in the signaling and transcriptional regulator, NOTCH1, are a cause of bicuspid aortic valve in non-syndromic autosomal dominant human pedigrees. The Notch signaling pathway is critical for multiple cellular processes during both development and disease and is expressed in the developing and adult aortic valve consistent with the cardiac phenotypes identified in affected family members. Recent work has begun to elucidate the molecular mechanisms underlying the link between Notch1 signaling and the development of BAV and valve calcification. Using in vitro approaches, loss of Notch signaling has been shown to contribute to aortic valve calcification via Runx2-, Sox9-, and Bmp2-dependent mechanisms. In addition, Notch1 signaling has been shown to be responsive to nitric oxide signaling during this disease process. A new highly penetrant mouse model of aortic valve disease using Notch1 haploinsufficient mice that are backcrossed in an endothelial nitric oxide synthase (Nos3)-null background was generated. Notch1 and Nos3 compound mutant mice (Notch1+/-;Nos3-/-) display a nearly 100 % incidence of aortic valve malformations, most commonly BAV. The aortic valves of adult mutant mice are thickened and have associated stenosis and regurgitation. Based upon the initial discovery of NOTCH1 mutations in humans with aortic valve disease, subsequent studies have provided significant molecular insights into BAV-associated diseases.


PMID: 29787141

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

Book. 2016

Authors: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H

Abstract
The heart is the first organ to develop in the embryo, and its formation is an exquisitely regulated process. Inherited mutations in genes required for cardiac development may cause congenital heart disease (CHD), manifested in the newborn or in the adult. Notch is an ancient, highly conserved signaling pathway that communicates adjacent cells to regulate cell fate specification, differentiation, and tissue patterning. Mutations in Notch signaling elements result in cardiac abnormalities in mice and humans, demonstrating an essential role for Notch in heart development. Recent work has shown that endocardial Notch activity orchestrates the early events as well as the patterning and morphogenesis of the ventricular chambers in the mouse and that inactivating mutations in the NOTCH pathway regulator MIND BOMB-1 (MIB1) cause left ventricular non-compaction (LVNC), a cardiomyopathy of poorly understood etiology. Here, we review these data that shed some light on the etiology of LVNC that at least in the case of that caused by MIB1 mutations has a developmental basis.


PMID: 29787142

Etiology and Morphogenesis of Congenital Heart Disease: From Gene Function and Cellular Interaction to Morphology

Book. 2016

Authors: Nakanishi T, Markwald RR, Baldwin HS, Keller BB, Srivastava D, Yamagishi H

Abstract
The significance of the epicardium that covers the heart and the roots of the great arteries should not be underestimated as it is a major component with impact on development, disease, and repair. The epicardium differentiates from the proepicardial organ located at the venous pole (vPEO). The differentiation capacities of the vPEO into epicardium-derived cells (EPDCs) have been extensively described. A hitherto escaped part of the epicardium derives from a second proepicardial organ located at the arterial pole (aPEO) and covers the intrapericardial part of the aorta and pulmonary trunk. In avian and mouse embryos, disturbance of epicardium differentiation causes a spectrum of cardiac anomalies including coronary artery abnormalities, deficient annulus fibrosis with rhythm disturbances, valve malformations, and non-compaction cardiomyopathies. Late in prenatal life the epicardium becomes dormant, losing the activity of many genes. In human cardiac diseases, both arterial and venous epicardium can be activated again into EPDCs. The epicardial reactivation observed after experimental myocardial infarction and during aneurysm formation of the ascending aorta provides clinical relevance. EPDCs applied for cell therapy demonstrate repair processes synergistic with the resident cardiac progenitor stem cells that probably share an embryonic origin with EPDCs. Future therapeutic strategies might be possible addressing cell autonomous-based and signaling capacities of the adult epicardium.


PMID: 29787150

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