Regression of Pulmonary Arteriovenous Malformations after Transcatheter Reconnection of the Pulmonary Arteries in Patients with Unidirectional Fontan

Aboulhosn, Jamil; Danon, Saar; Levi, Daniel S.; Castellon, Yelba; Child, John S.; Moore, John W.

doi:10.1111/j.1747-0803.2007.00094.x

Cited by 25 publications

(22 citation statements)

References 12 publications

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“…Any shunts that redirect blood flow from the lower body to the right lung result in complete resolution of AVMs, suggesting there is a hepatic factor that prevents the development of AVMs. 43 Indeed, BMP-9 is a circulating factor that, to our current knowledge, is made only in the liver. 44 Absence of BMP-9 may ease the ALK1-mediated suppression of VEGF, and explain why patients with end-stage liver disease with cavopulmonary anastomoses develop AVMs.…”

Section: Discussionmentioning

confidence: 99%

Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells

Shao

Lin²,

Yao³

et al. 2009

Blood

125

108

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Expression of vascular endothelial growth factor (VEGF) is tightly regulated to achieve normal angiogenesis. The objective was to examine regulation of VEGF by the activin-like kinase receptors (ALKs) ALK1 and ALK5. Transforming growth factor ␤1 (TGF␤1) and bone morphogenetic protein-9 (BMP-9) enhanced and suppressed VEGF expression, respectively, in aortic endothelial cells, as determined by real-time polymerase chain reaction, immunoblotting, cell proliferation, and tube formation. The use of small interfering RNA revealed that TGF␤1 stimulated VEGF expression by activating ALK5, TGF␤ type II receptor, and SMAD2, whereas BMP-9 suppressed it by activating ALK1, BMP type II receptor, and SMAD1. ALK1 signaling occurred independently of ALK5 activity. Partial ALK1 deficiency in vitro and in vivo resulted in elevated VEGF expression. In vitro, increased BMP-9 levels normalized VEGF expression in cells with partial, but not severe, ALK1 deficiency. Time course experiments revealed that an increase in ALK1 expression induced by BMP-4, an angiogenic stimulus, preceded induction of ALK5 and VEGF in control cells. In ALK1-deficient cells, however, VEGF expression occurred earlier and was abnormally high, even though ALK5 was not induced. Our results suggest that ALK1 and ALK5 are both essential for correct regulation of VEGF, and that disruption of either pathway leads to disease. (Blood. 2009;114:2197-2206) IntroductionVascular endothelial growth factor (VEGF) is a potent angiogenic factor that has been studied extensively as an agent promoting neovascularization in models of tissue ischemia. 1,2 It was discovered that increased VEGF expression resulted in the formation of large, dilated, and fragile blood vessels, which resembled arteriovenous malformations (AVM). [2][3][4] Interestingly, elevated plasma levels of VEGF have been previously reported in patients with the disease hereditary hemorrhagic telangiectasia (HHT), 3,5 the hallmark of which is the development of AVM. HHT is associated with mutations of endoglin or activin-like kinase receptor-1 (ALK1), both receptors for members of the transforming growth factor ␤ (TGF␤) superfamily. [6][7][8] We and others have previously reported that the ligand TGF␤1 induces the expression of VEGF. [9][10][11][12][13] In addition, He and Chen reported the presence in zebrafish of binding elements on VEGF promoter for SMAD proteins, the downstream mediators of TGF␤ signaling, supporting that VEGF expression is regulated by the TGF␤ family. 14 To activate TGF␤ signaling, the TGF␤ ligand binds to a type II receptor, which becomes activated through autophosphorylation. The activated type II receptor recruits and activates a type I receptor by transphosphorylation and the activated heterodimeric complex, and then activates an intracellular SMAD protein also by transphosphorylation. Activated SMAD binds to a co-SMAD (a SMAD with a nuclear localizing sequence), and the heterodimeric SMAD complex enters the nucleus to regulate target gene expression. 15 Both ALK1 and ALK5 are type I ...

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Section: Discussionmentioning

confidence: 99%

Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells

Shao

Lin²,

Yao³

et al. 2009

Blood

125

108

View full text Add to dashboard Cite

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“…In animals, our group and others have used needle (12) and radiofrequency perforation (23) for unidirectional “classic” Glenn shunts (SVC solely to the right PA) and more recently the contemporary, and more technically demanding, bidirectional (both PAs) version (13). In post-operative Fontan patient case reports, small pulmonary artery-to-atria fenestrations (24) and medium-sized PA reconnections (25) have been created. In unoperated patients, sharp wire puncture was used to create a restrictive 7 mm transcatheter Potts shunt (small descending thoracic aorta to left PA communication) surrogate in a small number of adults with end-stage PA hypertension (26).…”

Section: Discussionmentioning

confidence: 99%

First-in-Human Closed-Chest Transcatheter Superior Cavopulmonary Anastomosis

Ratnayaka

Moore

Rios

et al. 2017

Journal of the American College of Cardiology

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BACKGROUND In the care of patients with congenital heart disease, percutaneous interventional treatments have supplanted many surgical approaches for simple lesions, such as atrial septal defect. By contrast, complex congenital heart defects continue to require open-heart surgery. In single-ventricle patients, a staged approach is employed, which requires multiple open-heart surgeries and significant attendant morbidity and mortality. A nonsurgical transcatheter alternative would be attractive. OBJECTIVES We sought to show the feasibility of catheter-only, closed-chest, large-vessel anastomosis (superior vena cava and pulmonary artery [PA] or bidirectional Glenn operation equivalent) in a patient. METHODS In preclinical testing over a decade, we developed the techniques and technology needed for nonsurgical crossing from a donor (superior vena cava) to a recipient (PA) vessel and endovascular stent-based anastomosis of those blood vessels. We undertook this transcatheter approach for an adult with untreated congenital heart disease with severe cyanosis and significant surgical risk. We rehearsed the procedure step by step using contrast-enhanced cardiac computed tomography and a patient-specific 3-dimensional printed heart model. RESULTS We described a first-in-human, fully percutaneous superior cavopulmonary anastomosis (bidirectional Glenn operation equivalent). The patient, a 35-year-old woman, was homebound due to dyspnea and worsening cyanosis. She was diagnosed with functional single ventricle and very limited pulmonary blood flow. The heart team believed surgical palliation conferred high operative risk due to the patient’s complete condition. With the percutaneous procedure, the patient suffered little morbidity and remained improved clinically after 6 months. CONCLUSIONS This procedure may provide a viable alternative to one of the foundational open-heart surgeries currently performed to treat single-ventricle congenital heart disease.

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“…While it is not known what concentration of this hepatic factor is required for normal lung development, it is clear that an unbalanced hepatic flow distribution to the left and right lungs due to an inadequate design of the IVC-to-PA conduit during the 3 rd stage of the TCPC surgery puts patients at risk for PAVMs. Clinically, once the extent of PAVMs is such that oxygen saturation is critically low, the only palliative option is to re-operate and re-orient the IVC conduit to achieve a better hepatic flow distribution (Uemura, Yagihara et al 1999; Steinberg, Alfieris et al 2003; Pike, Vricella et al 2004; Wu and Nguyen 2006; AboulHosn, Danon et al 2007). …”

Section: Single-ventricle Heart Defects: Review Of the Clinical Prmentioning

confidence: 99%

“…Several palliative options have been discussed in the literature(Stamm, Friehs et al 2002; Pike, Vricella et al 2004; AboulHosn, Danon et al 2007), but clearly the wide variety of patient anatomies makes it difficult to design a general “one-size-fits-all” procedure for Fontan patients. In parallel, the complexity and variability of in vivo anatomies pose significant clinical challenges to identify the surgical option for a given patient, i.e.…”

Section: Single-ventricle Heart Defects: Review Of the Clinical Prmentioning

confidence: 99%

Imaging and patient-specific simulations for the Fontan surgery: Current methodologies and clinical applications

Zélicourt

Marsden

Fogel

et al. 2010

Progress in Pediatric Cardiology

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Regression of Pulmonary Arteriovenous Malformations after Transcatheter Reconnection of the Pulmonary Arteries in Patients with Unidirectional Fontan

Abstract: Patients with unidirectional Fontan and PAVM demonstrate increased oxygen saturations following reconnection of PAs, suggesting regression of PAVM. This procedure can be performed safely using uncovered stents, and it is effective in improving systemic oxygen saturations.

Cited by 25 publications

References 12 publications

Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells

Expression of vascular endothelial growth factor is coordinately regulated by the activin-like kinase receptors 1 and 5 in endothelial cells

First-in-Human Closed-Chest Transcatheter Superior Cavopulmonary Anastomosis

Imaging and patient-specific simulations for the Fontan surgery: Current methodologies and clinical applications

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