\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
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\r\n\tBrain-Computer Interfacing (BCI) is a rapidly growing field of bioengineering that allows the human brain to directly control the computer system and order commands. The aerospace systems, automotive industry, medical and healthcare system, security, lie detection, alertness monitoring, telepresence, gaming, education, art and other fields and industries are potential beneficiaries of the research in this field.
\r\n\r\n\tThis book will cover recent progress in the field of BCI and the challenges for extraction of the human decisions out of brain signals. The presented topics will include neuroscience, recording BCI Signals, signal processing, artifact reduction, machine learning, invasive and noninvasive methods and applications of BCI and ethics.
\r\n\r\n\tThe book will be designed as a reference for senior undergraduate and graduate students in neural engineering or brain-computer interfacing from a wide range of disciplines. It will also be useful for self-study and as a reference for neuroscientists, computer scientists, bioengineers, and medical practitioners.
",isbn:"978-1-83962-529-9",printIsbn:"978-1-83962-522-0",pdfIsbn:"978-1-83962-530-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,hash:"a5308884068cc53ed31c6baba756857f",bookSignature:"Dr. Vahid Asadpour",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/10654.jpg",keywords:"Connections Adapting, Synaptic Plasticity, Non-Invasive Techniques, Signal Processing, Simultaneous Recording and Stimulation, Spike Sorting, Discrete Fourier Transform, Machine Learning, Neural Networks, Non-Invasive BCIs, Medical Applications, Sensory Restoration",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"January 11th 2021",dateEndSecondStepPublish:"February 8th 2021",dateEndThirdStepPublish:"April 9th 2021",dateEndFourthStepPublish:"June 28th 2021",dateEndFifthStepPublish:"August 27th 2021",remainingDaysToSecondStep:"17 days",secondStepPassed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Asadpour is a researcher in the field of artificial intelligence for medical and bioengineering applications, and an investigator in multiple projects funded by the National Institute of Health (NIH).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"165328",title:"Dr.",name:"Vahid",middleName:null,surname:"Asadpour",slug:"vahid-asadpour",fullName:"Vahid Asadpour",profilePictureURL:"https://mts.intechopen.com/storage/users/165328/images/system/165328.jpg",biography:"Vahid Asadpour is currently with Photonic Laboratory of University of California Los Angeles (UCLA). He graduated from Polytechnic University of Tehran achieving M.S. and PH.D. degree in biomedical engineering. He was a visiting professor and researcher at University of North Dakota (UND). He is working in the field of artificial intelligence and machine learning and their applications in digital signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. He developed brain computer interfacing algorithms and published one book chapter and several journal and conference papers in this field and other areas of intelligent signal processing. Adding to his professional experimental skills, he also designed medical devices including a laser Doppler monitoring system and therapeutic drug estimation algorithm. He is also affiliated with Polytechnic University of Sadjad.",institutionString:"University of California Los Angeles",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"University of California Los Angeles",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"194667",firstName:"Marijana",lastName:"Francetic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/194667/images/4752_n.jpg",email:"marijana@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"878",title:"Phytochemicals",subtitle:"A Global Perspective of Their Role in Nutrition and Health",isOpenForSubmission:!1,hash:"ec77671f63975ef2d16192897deb6835",slug:"phytochemicals-a-global-perspective-of-their-role-in-nutrition-and-health",bookSignature:"Venketeshwer Rao",coverURL:"https://cdn.intechopen.com/books/images_new/878.jpg",editedByType:"Edited by",editors:[{id:"82663",title:"Dr.",name:"Venketeshwer",surname:"Rao",slug:"venketeshwer-rao",fullName:"Venketeshwer Rao"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"4816",title:"Face Recognition",subtitle:null,isOpenForSubmission:!1,hash:"146063b5359146b7718ea86bad47c8eb",slug:"face_recognition",bookSignature:"Kresimir Delac and Mislav Grgic",coverURL:"https://cdn.intechopen.com/books/images_new/4816.jpg",editedByType:"Edited by",editors:[{id:"528",title:"Dr.",name:"Kresimir",surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3621",title:"Silver Nanoparticles",subtitle:null,isOpenForSubmission:!1,hash:null,slug:"silver-nanoparticles",bookSignature:"David Pozo Perez",coverURL:"https://cdn.intechopen.com/books/images_new/3621.jpg",editedByType:"Edited by",editors:[{id:"6667",title:"Dr.",name:"David",surname:"Pozo",slug:"david-pozo",fullName:"David Pozo"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"60384",title:"Silver Nanoparticle Incorporated Titanium Oxide for Bacterial Inactivation and Dye Degradation",doi:"10.5772/intechopen.75918",slug:"silver-nanoparticle-incorporated-titanium-oxide-for-bacterial-inactivation-and-dye-degradation",body:'\nTitanium dioxide (TiO2) exists in three different crystal structures that are anatase, rutile, and brookite, where rutile is known as the most stable form [1]. The band gap energy of anatase, rutile, and brookite are 3.2, 3.0, 3.2 eV, respectively [1, 2, 3, 4, 5]. It means that they can only be activated with UV light irradiation having a wavelength (λ) of 387 nm or lower. Many studies in the area show the use of UV radiation as a photon source for both photocatalytic inactivation of microorganisms [6, 7, 8, 9, 10, 11] and dye degradation [12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30].
\nThe titania has been employed as a photocatalyst in several photocatalytic reactions due to its high photoactivity, low cost, low toxicity and good chemical and thermal stability [1, 2, 3]. However, its large energy band gap inhibits it from being active under UV light [31, 32, 33, 34, 35]. The solar spectrum consists of only 4–5% UV light and around 40% visible light [31].Therefore, the efficiency of TiO2 as a photocatalyst under sunlight irradiation is limited.
\nModification of TiO2 to improve the photocatalytic efficiency of TiO2 under sunlight visible irradiation is necessary. The modification by non-metal [36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51] and metal [52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83] doping on TiO2 has been attempted. The metal doping agents introduced for TiO2 are transition metals (Fe, Cu, Cr, Co, and Ni) [52, 53, 54, 55, 56] and noble metals (Ag, Au, Pd, and Pt) [57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83]. Among the noble metals, silver has received considerable interest due to its additional potential as an antibacterial agent [84]. The importance of medical applications of metallic silver [85, 86] and antibacterial activity of TiO2 [6, 7, 8, 9, 10, 11] attracts researchers to think of manufacturing silver-doped titania. There are ongoing works related with the use of Ag for possible medical devices [79], dental implants [78, 79], food packagings [80], air conditioning filters, and so on [79]. Some works focus on bacterial inactivation [34, 63] and dye waste treatment under visible light irradiation [66, 67, 81, 82, 83]. Hence, the preparation and characterization of the TiO2-based photocatalyst and its activity are presented.
\nThe sol-gel method involves the interaction of titania sol with silver ion the solution, which forms a gel. The gel is heated at a low temperature to evaporate the solvent followed by calcination at high temperature [31, 35, 72, 73, 78, 80, 82, 83]. The main precursor of titania is commonly liquid titanium(IV) isopropoxide (TTiP) with a chemical formula of Ti(OC3H7)4 [31, 35, 72, 75], but titanium n-butoxide (Ti(OC4H9)4 [82, 83] is also potential. For silver starting material, AgNO3 is frequently employed [31, 72, 75, 77, 80, 82, 83]; however, silver acetylacetonate is also chosen sometime [35].
\nTitania sol is prepared by mixing TTip solution in ethanol and water accompanied by stirring vigorously at room temperature for about 15 min. During the dissolution of TTip in the ethanol medium, an exchange of propyl group from TTip with ethyl group from the ethanol to yield titania tetra ethoxides takes places by the release of propanol. Titanium tetra ethoxide is hydrolyzed in acidic medium to form sol titanol of Ti(OH)4.
\nThe AgNO3 solution is mixed with ethanol and stirred [31, 72, 75, 77, 80, 82, 83], giving the sol of silver. Finally, the silver sol is added dropwise to the titania sol with stirring, where transparent titania sol changes its viscous yellow solution. The reaction between titania sol and silver sol is commonly written as follows:
\nThe viscous sol was heated at about 60°C to evaporate organic solvents to yield dry gel [72]. The dry gel is calcined at about 350°C to produce TiO2-AgNP powders, according to the reaction (2):
\nIn the preparation of TiO2-AgNP photocatalyst by a sol-gel method, some modifications have been done including the use of acetic acid [83], micellar medium [75], spin coating technique [82], with the purpose to improve TiO2-AgNP photocatalyst characteristics and performance.
\nThe synthesis of TiO2-AgNP by impregnation method is carried out by stirring the solution of AgNO3 mixed with the suspension of TiO2 in water for 24 h. The solvent is later removed by drying at 150°C followed with calcination of the product at 500°C [68]. Some modifications in the impregnation method such as the use of capping agent [74] and combustion method [63, 64] are also possible.
\nThe modification starts with silver nanoparticles preparation in polyvinylpyrrolidone (PVP) as a capping agent. For this purpose, the AgNO3 solution is added to methanol and is mixed with PVP. The mixture is refluxed for 3 h at 110°C to give a yellow-orange color solution. The solvent was evaporated at 55°C, and the obtained Ag nanoparticles were dispersed into ethanol and thoroughly washed with hexane and ethanol. The Ag nanoparticles are redispersed into the ethanol under sonication, and TiO2 powder is added to the solution. This mixture is sonicated for 3 h and is dried at 60°C to remove the solvent followed temperature rise to 90°C [74].
\nThe combustion method is carried out by heating a mixture of AgNO3, titanyl nitrate and glycine as fuel in the muffle furnace at 150°C for 2 h [63, 64]. The remaining solid from the combustion is supposed to be TiO2-AgNP.
\nIn the precipitation method, titanium tetra-isopropoxide and silver nitrate were used as a source of titanium and silver, respectively. Ag-doped TiO2 nanocrystalline powder was prepared by controlled addition of TTIP to absolute ethanol with constant stirring to get a clear solution. A sufficient amount of surfactant solutions (1% CTAB +1% SDS) was added to the solution with constant stirring. The aqueous solution of silver nitrate was added to the solution. A solution of aqueous ammonia was added dropwise to the last solution under stirring with the special arrangement at room temperature until the solution pH reaches 8. After complete precipitation, the solid was washed with Millipore deionized water and acetone several times to remove excess of surfactant. The precipitate was kept under microwave irradiation for 20 min. The dried powder was ground and calcined at 300°C for 3 h in a temperature-controlled muffle furnace [68]. Following calcination, the TiO2-AgNP was obtained.
\nIn this method, the TiO2 powder is dispersed into ethanol and water, followed by stirring or sonicating for about 15 min to form titania sol. The AgNO3 solution is added to the sol. The mixture is irradiated with UV lamp for a certain period of time along with constant stirring. After a certain time, the solid was separated by filtration and dried at around 300–400°C [31, 33, 67, 69, 70, 71, 73, 79, 81]. In this method, when TiO2 photocatalyst is exposed to UV light, electrons are revealed along with the formation of OH radicals. The electrons will interact with Ag+ coming from AgNO3 resulting in the reduction reaction of the Ag+ to form Ag0 metallic particles. The small particle of Ag0 can be inserted into the crystal lattices of TiO2 [67] and/or deposited onto TiO2 surface to form a small cluster.
\nThe content of Ag incorporated in the TiO2 crystal structure prepared by sol-gel, precipitation and photodeposition can be determined by elemental analyses by X-Ray Fluorescence (XRF) [68, 75], ICP-MS [35] and atomic absorption spectrophotometry (AAS) [83]. In general, the content of Ag formed in TiO2-AgNP is proportional to the initial concentration of precursors of the AgNO3 solution.
\nThe presence of Ag in the TiO2-AgNP can be detected by XRD method. It can be carried out by detecting X-ray diffraction pattern evolution with the reference of native TiO2. The XRD pattern of TiO2 recorded by using a CuKα source of XRD machine gives several characteristics peaks of 2θ values at 25.091, 37.651, 48.021, 53.891, 55.071, 62.381, 68.701, 70.041 and 75.001. These peaks are confirmed with JCPD Card No. (21-1272) and are attributed to the diffraction of TiO2 anatase. They correspond to the lattice planes (101), (004), (200), (105), (211), (204), (220), (220), and (215), respectively [67, 68, 77, 82]. In many instances, Ag is not detected in the XRD pattern. It is probably located in bulk (inside the TiO2 crystals) [77], and/or Ag clusters smaller than 0.3 nm [66], or diffused in the TiO2 crystal lattice [68], or well dispersed throughout the TiO2 surface [31] (Figure 1).
\nXRD patterns of (a) TiO2, (b) TiO2/Ag-0.05%, (c) TiO2/Ag-0.10%, (d) TiO2/g-0.15%,(e) TiO2/Ag-0.25%, and (f) TiO2/Ag-0.50% [71].
High Ag content (more than 0.25 mol%) in TiO2-AgNP prepared by precipitation assisted with microwave [68] and that of by photocatalytic reduction [67] have additional diffraction peaks at 2θ values of 38.011, 44.261, 64.021 and 77.361. The appearance of the peaks can be assigned to the face centered cubic lattice planes of metallic silver of (111), (200), (200) and (311) planes, respectively [67, 68]. It is evident that TiO2-AgNP photocatalyst with low metallic Ag content is undetectable by the XRD technique [82]. The detectable metallic Ag level is found to be more than 0.80 moles% [66], but 0.25 moles% or higher is also reported [68]. Depending on the concentration, the detectable metallic silver in TiO2-AgNP is also observed in the XRD pattern when TiO2-AgNP is calcined at a higher temperature (700°C) since sintering step causes Ag particles to form large aggregate [31].
\nThe valence state of silver, as ionic Ag+ or metallic silver Ag0, in the TiO2-AgNP photocatalyst can be distinguished by XPS. The XPS spectrum shows the characteristic Ag 3d peak that has a binding energy of 368 eV with a 6.0 eV splitting of the 3d doublet of low spin 3d1/2 and high spin 3d5/2 [33]. It confirms that the presence of metallic silver deposits on the TiO2 [33]. It is different from the XRD data that can only provide the metallic silver in high level; the XPS gives additional proof that the metallic silvers are formed in TiO2-AgNP at all concentration levels.
\nThe existence of Ag in TiO2-AgNP can also be distinguished by temperature-programmed reduction (TPR) spectrometry technique. The profile of the TPR spectra of sol-gel TiO2-AgNP calcined at 350°C [72] shows reduction peak at around 135°C, which suggests a reduction of Ag+ into Ag0 metallic without interacting with the support. Also, TiO2-AgNP calcined at 500°C give spectra peak at around 350 and 500°C, probably due to Ag reduction with support material [72].
\nThe incorporation of Ag on TiO2 is meant to allow the TiO2 to be active under visible light. The photocatalytic ability of TiO2 photocatalyst under visible is assigned by the lower band gap energy (Eg) or absorption in visible light. The band gap energy (Eg) can be determined based on the data of the maximum absorption wavelength (λ) according to the equation Eg = 1239/λ, where the maximum absorption wavelength is obtained from the diffuse reflectance (DR) data [67].
\nThe DR-spectra at 200–800 nm of TiO2 displays that the maximum absorption is seen at around 400–390 nm corresponding to 3.15–3.20 eV of the band gap energy of anatase [1, 2, 3]. Furthermore, the metallic silver loading on TiO2 is observed to shift the maximum absorption to a longer wavelength that is about 430–574 nm [31, 66, 67, 72, 75, 81]. The DR spectra give respective band gap energy as much as 2.88–2.16 eV. The absorption wavelength or the band gap energy values allow the TiO2-AgNP photocatalyst to be active in the visible region. The absorption shift may be resulted by the diffusion of the metallic silver into the crystal lattice of the TiO2 structure that the silver to be dispersed or inserted between the conduction and valence bands of the host material [31, 67, 75] (Figure 2).
\nDR spectra, from the top in order representing TiO2, TiO2/Ag-0.05%, TiO2/Ag-0.25%, and TiO2/Ag-0.50% [71].
The absorption shift is found to be affected by Ag content in TiO2-AgNP [67, 68, 75, 81], the preparation method of TiO2-AgNP, and calcination temperature [72]. The shift increases with the increasing Ag amount in TiO2 because more Ag inserted into the gap so that the gap becomes narrower than that of bare TiO2, shifting in the absorption wavelength to increase. Based on the preparation method, TiO2-AgNP photocatalyst prepared by sol-gel has a more substantial shift in the wavelength than the ones produced by the impregnation method [72]. In the sol-gel process, the silver ion (Ag+) having a small size interacts with the titania sol, allowing the ion to disperse into the crystal lattice of TiO2. Meanwhile, in the impregnation the silver introduced into the titania sol present as AgNO3 salt is difficult to penetrate the lattice [75], giving less effect on the band gap. The final step in the TiO2-AgNP preparation process is calcination at a higher temperature that is about 350–500°C. The high calcination temperature of TiO2-AgNP gives smaller absorption shift than the low calcination temperature [72]. With a high temperature, the silver sintering on TiO2 may be occurred to form bigger Ag metallic cluster, which prevents it from entering the gap. The significant shift of the absorption wavelength is expected because this should promote higher photocatalyst activity in the visible region.
\nThe diffusion of Ag into the crystal lattice of TiO2 may enlarge its basal spacing (d) that can be confirmed by their basal spacing obtained from the XRD patterns. It is found that the presence of Ag in the TiO2-AgNP causes the XRD peak position of TiO2 shifts to a low 2θ angle. Further, the 2θ angle position is getting lower as the Ag content increases. The 2θ angle value is related to the basal spacing (d) of TiO2 crystal as represented by Bragg’s equation [68]:
\nThe equation describes the smaller sin θ value, the larger the d spacing. It is known that the value of d increases gradually with increase in Ag contents. The enlargement of the XRD basal spacing (d) implies that more silver diffuses into the lattice of TiO2 [68]. As the Ag contents increasing from 0 to 0.25 mol%, the peak broadening of [101] planes gradually increases, which indicates the smaller crystallite size of Ag. The smaller size facilitates them to diffuse into the crystal lattice easily.
\nThe insertion of the metallic silver into the TiO2 crystal lattice may distort the structure of TiO2 or disturb the chemical bonds of Ti-O in the solid. To better understand the effect of the Ag as a doping agent, the spectrometer data of IR is used. The FTIR spectra of both TiO2 and TiO2-AgNP photocatalyst illustrating several absorptions appear at various wavelengths [68, 77, 81]. A broad peak at 3448 cm−1 represents O-H stretching of Ti-O-H. Also, a peak seen at 1635 cm−1 is due to the OH bending mode of water adsorbed on the surface of TiO2. The peaks at the wavelength of 540 and 678 cm−1 are also observed due to Ti-O-Ti stretching and Ti-O-Ti bending, respectively [68, 75]. After loading Ag on TiO2, the peaks at 540 and 679 cm−1 shifts to 556 and 694 cm−1, respectively. The shifts may be affected by the interaction between Ag and TiO2 to form Ti-O-Ag composite and/or the insertion of Ag into host lattice of TiO2 [68].
\nThe XRD patterns confirm the distortion of the TiO2 structure after doping with metallic Ag. The XRD peaks belonged to both TiO2 and TiO2-AgNP seemed similar, but the peak intensity decreases after Ag loading. The intensity decreases imply the alteration of the crystallinity due to the insertion of Ag into the lattice of the TiO2 crystal [67].
\nThe Ag incorporation into the TiO2 may affect several important properties including particle size and surface area. The particle size determines its surface area, where the smaller the grain size, the larger the surface area. TEM can trace the particle size of Ag in TiO2-AgNP. The TEM image displays that the size varied with the Ag content in the TiO2-AgNP [33, 67]. For the two atomic% Ag in TiO2-AgNP sample, Ag deposits are well dispersed on the TiO2 particles with an average particle size of 2–4 nm. At high silver level, the formation of large Ag particles (>100 nm) is observed in the TEM images [33, 67]. The particle size of Ag-doped TiO2 is also directed by the preparation methods [33]. In TiO2-AgNP prepared by the impregnation method, Ag is detected to have a larger size than that of sol-gel. In the impregnation process, AgNO3 salt and TiO2 are suspended in water in the TiO2-AgNP preparation [33]. Consequently, the Ag particle is not limited by the TiO2 structure that enables them to form a large agglomerate. Meanwhile, in the sol-gel method, TiO2-AgNP is prepared from titania sol and Ag+ solution that allows them to have mutual interaction and inhibit their particle growth. As a result, it forms the small grain size (Figure 3).
\nThe TEM images of (a) TiO2/Ag-0.05%, (b) TiO2/Ag-0.25%, and (c) TiO2/Ag-0.50% [71].
The surface area is determined by surface area analyzer based on the BET method. In general, the surface area of TiO2-AgNP is controlled by the Ag content in TiO2-AgNP, preparation method, and the calcination temperature [33, 68, 72]. The surface area of TiO2-AgNP prepared by impregnation method is observed to decrease with increase in the Ag-doped TiO2 [72]. By impregnation method, the metallic silver is formed as large agglomerate that may block the surface of the TiO2 particle. Such surface blocking leads to the surface area to decline. In contrast, by a sol-gel method, the surface area increases with the enlargement of Ag content in TiO2-AgNP. The particle size of the metallic Ag is small due to the limitation of particle growth.
\nBy the photo-deposition method, the addition of Ag at only 0.25 mol%, an appreciable increase in the specific surface area is observed [33, 68]. The surface area of TiO2-AgNP with Ag content smaller than 0.25 mol% is not significantly different from that of the pure TiO2 due to the vast and thin dispersion of the Ag particles on the TiO2 structure. Ag in TiO2-AgNP as much as 0.25 mol% seems to be well dispersed on the surface of the TiO2 grain that contributes to a large surface area. The Ag loading higher than 0.25 mol% leads to the decrease in surface area that is resulted from by large silver aggregate.
\nThe other reasons for the surface area improvement are proposed as follows [31, 68, 76]. The Ag doping with a suitable amount (ca. 2–6 mol%) promotes the phase transformation of TiO2 from anatase to rutile since the surface area of rutile is larger than that of the anatase. The Ag-doped TiO2 also has a depressing effect on the anatase grain growth. The average crystallite size of the TiO2 can be calculated by using the Scherrer’s Equation [31]. It is observed that the TiO2 crystallite has an average size of 15 nm, and it decreases up to 10 nm for 0.25 mol% of Ag loading [68]. It is also confirmed that the decreasing the crystallite size increases the specific surface area of the TiO2 powder.
\nThe doping TiO2 with metallic Ag is intended to activate TiO2-AgNP photocatalyst under visible light both for bacterial inactivation and dye photodegradation.
\nThe doping TiO2 with metallic silver to produce TiO2-AgNP has been investigated as a potential antibacterial agent in inactivating Escherichia coli [63, 64, 65, 78, 79] under visible light exposure. The TiO2-AgNP exposure to UV light for bacterial inactivation is also essential.
\nTiO2-AgNP demonstrates a significant activity in the bacterial inactivation under visible light. The antibacterial performance of TiO2-AgNP is found to be higher than that of unmodified TiO2. Both TiO2 and TiO2-AgNP can kill bacteria because TiO2 provides OH radicals during UV or visible irradiation at a suitable wavelength. The OH radicals attack and destroy the bacterial wall [10, 11]. Under visible light, TiO2-AgNP can be activated since TiO2-AgNP has a low band gap energy (Eg) that matches with the visible region wavelength. Meanwhile, due to its high band gap energy (Eg), which is in the same order as UV light, TiO2 is less active under visible light. Addition of Ag to TiO2 also gives the excellent antibacterial agent, that is by penetrating the metallic Ag nanoparticles into the cell membrane of the bacteria [84]. There is a synergic effect of TiO2 and Ag in inhibiting bacteria [63, 64, 65, 78, 79]. The activity of Ag in the bacteria inactivation process is examined by applying TiO2-AgNP in dark condition [81]. It has been postulated that silver disrupts the cell wall and affects the rapid penetration of the metallic ions into the cell where irreversible precipitation of the bacteria’s DNA occurs [84].
\nThe role of Ag in TiO2-AgNP in the bacterial inhibition under visible light is affected by its ability as a center of the separation of photoinduced electron and OH radicals that delay the recombination of electron and hole [34, 63, 64, 65, 78, 79]. The other role of Ag in the improving the bacterial inactivation corresponds to the electron capture that can prevent the recombination. The inhibition of the recombination creates more OH radicals, which improves the bacterial inactivation.
\nThe Ag content in TiO2-AgNP is subjected to test further. Increase in Ag content leads to decline in bacterial inactivation [34, 63, 64, 65, 78, 79]. Increasing Ag in TiO2-AgNP can enhance the electron capture, forming anion Ag, which allows more OH radical available. The more OH radicals available, the better bacterial inactivation. However, a further increase in Ag content can block the TiO2 surface and prevent the light absorption, producing a lower amount of OH radicals. The other possible reason is the attachment of OH radical with excess Ag anion. The depletion of OH radicals leads to the inactivation declined [64].
\nComparing between the bacterial inactivation under UV and visible light with and without photocatalyst, it is similar to the UV photolysis system [63, 64]. Visible light photolysis alone is observed to play a role in microorganism inactivation. The bacterial inactivation in UV-A or visible light is observed due to the synergetic effects of radiating energy and mild heat produced during the irradiation [63]. In the presence of TiO2-AgNP photocatalyst, it is found the rates of inactivation were higher in the presence of UV than that of visible light.
\nUV light has germicidal property, and TiO2 itself possesses higher photocatalytic activity in UV region due to its large band gap energy. On the other hand, doping with metal is mainly done to extend the absorbance of TiO2 to the visible region. Therefore, the photocatalytic inactivation in the presence of UV light and TiO2: Ag catalyst is a synergetic effect of antimicrobial property of silver, the germicidal property of UV and photocatalytic activity of the TiO2 photocatalyst [63, 64]. It should be noted that the antibacterial inactivation is dependent on several operating conditions such as visible light intensity and catalyst amount.
\nPhotocatalytic inactivation reactions are highly dependent on the irradiation intensity of the light source [34, 63]. The increase in the visible light intensity from 2 to 8 W.m2 can enhance the bacterial inactivation over TiO2-AgNP photocatalysts. The observed enhancement in the inactivation is due to the increase in the number of photons produced as light intensity rise.
\nThe addition of catalyst to the solution resulted in a better bacterial inactivation than the control experiments. At low catalyst dose (0.1 g/L), the observed inactivation was not significant because of less availability of OH radicals to target a large number of bacteria. The increase in the photocatalyst dose to 0.25 g/L shows the possibility of an increase in the number of OH radicals sufficient enough to target the microorganism number, which improves bacterial inactivation. At 0.25 g/L, the maximum inactivation shows the maximum availability of OH radicals in the solution. When the photocatalyst loading is increased above 0.25 g/L, the inactivation process becomes slow where more bacterial colonies are detected for photocatalyst loading of 0.5 and 1.0 g/L. A high amount of catalyst in the solution results in turbidity increase that blocks the radiation to reach to microorganisms and other catalyst particles (shadowing or screening effect), which leads to a low rate of inactivation. The similar effect is observed for the UV photocatalytic inactivation [63, 64].
\nIt is reported that the inactivation of bacteria was not influenced by changing the pH of the solution. The rate constant also remains constant for all pH range [64]. The zero point of charge (ZPC) for TiO2-AgNP and E. coli can be estimated as ZPC (TiO2-AgNP) = 4.0 and ZPC (E. coli) = 2.5, respectively. At all the pH values studied, both E. coli and the catalyst had a negative surface charge. Therefore, the electrostatic repulsion between bacterial cells and catalyst particles could result in the similar inactivation effect.
\nThe performance of TiO2-AgNP photocatalyst is investigated for dye photodegradation under visible light. Among dyes studied as examples in photodegradation test include methylene blue [31, 66], rhodamine-B (RD-B) [33], and acid read 8S [67].
\nTiO2-AgNP photocatalyst shows higher activity under visible light in the photodegradation of dyes than that of bare TiO2 [33, 31]. It means that TiO2-AgNP is also photoactive in the visible region. The energy of the visible light (2.2–3.0 eV) is near the band gap energy of TiO2-AgNP, which is about 2.7–2.9 eV [72, 75]. The visible light is required to activate TiO2-AgNP for the dye photodegradation. The energy of the visible light is slightly lower than the band gap of TiO2 anatase (3.2 eV) and TiO2 rutile (3.0 eV). The visible light is unable to excite an electron in TiO2. Therefore, the photocatalytic performance of TiO2 is weak.
\nIncreasing Ag content in TiO2-AgNP promotes photodegradation as shown in many works. But further increase in Ag content could have a detrimental effect on the photodegradation result [31, 33, 66, 68]. The optimum Ag content in TiO2-AgNP is found be at about 2.5 w% [33], 0.80% mol [66], and 0.25 mol% [68].
\nThe effect of Ag content in TiO2-AgNP on photocatalytic activity can be explained as follows. The appropriate amount of Ag-doped TiO2 allows effective capture of the photoinduced electrons [31, 33, 66, 67]. The photoinduced electrons during light irradiation results in negatively charged Ag. The photoinduced electrons can be immediately transferred to oxygen atoms of TiO2. The electron transfer from the TiO2 conduction band to metallic silver particles at the interface is thermodynamically favorable because the Fermi level of TiO2 is higher than that of silver metals [31, 33]. It results in the formation of the Schottky barrier at metal-semiconductor contact region, which improves the charge separation. Accordingly, the recombination of the electron and the OH radicals can be inhibited more [33]. This condition explains the significant enhancement of the photocatalytic activity of TiO2-AgNP. The increase in Ag content will keep the photodegradation improve until it reaches its optimum.
\nAt high Ag loading above its optimum level, an excess amount of negatively charged silver species are available. A significant amount of the negatively charged silver particles allows silver atoms to attract more OH radicals. However, it reduces charge separation efficiency [31, 35, 66] or raises electron-hole recombination and decrease dye photodegradation. Another possible reason is the formation of silver metallic clusters inside the TiO2 crystal. The metal clusters give small contact surface area of the photocatalyst. The atomic Ag in TiO2-AgNP may act as a barrier to obstruct light absorption by titania. It also prevents organic substrates from contacting the photocatalyst surface. Silver atoms may become media for electron-hole recombination [44]. As a result, they reduce photodegradation reaction.
\nThe photocatalyst working under the UV light is frequently assessed for dye photodegradation such as methyl orange [68], diazo type dye of DR 23 and DB 53 [69, 70] and methylene blue [74, 82]. It is evident that in the presence of Ag, the photocatalytic performance of the TiO2-AgNP under UV light improves. The photocatalytic activity of TiO2-AgNP under the UV light is higher than that of unmodified one. The role of the Ag in the improvement of the dye photodegradation under UV light can explain similarly to the effect of Ag under visible light.
\nThe photodegradation performance of TiO2-AgNP under visible light is better than under UV light. In the case of rhodamine-B degradation, the dye can be adsorbed by Ag particle in TiO2-AgNP. The dye adsorbed on the Ag surface can be activated by visible light because the dye absorbs the electromagnetic radiation in the range of visible light. The activated dye molecules are unstable and start to degrade. On the one hand, the lower UV light photocatalytic activity of TiO2-AgNP may be due to surface plasmon resonance of metallic Ag that reduces UV light excitation [66]. This unexcitability of the photocatalyst leads to the low dye photodegradation.
\nThe dye photodegradation of dye by TiO2-AgNP under UV light is controlled by the level of Ag in photocatalysts and irradiation light. Also, the effectiveness of the dye photodegradation is affected by operating conditions such as photocatalyst dose, initial concentration, contact time and solution pH.
\nThe dye photodegradation increases with the increase in the photocatalyst dose. The effectiveness of the photodegradation reduces when the photocatalyst dose is further increased [66, 67, 68, 81]. The maximum photodegradation is obtained by using 1 g photocatalyst/100 mL [68, 74, 81]. In other work, the use of 0.6 g photocatalyst/L is also reported [67]. Such data can be explained based on the number of active sites available for photocatalytic reactions. More active sites of the photocatalyst are available when the dose of the photocatalyst increases. However, the use of a large number of photocatalysts may cause agglomeration of the material to produce big particle size. The large particle size gives small surface area, which decreases the number of active sites on the surface [36, 38]. Another reason for the decrease in the degradation can be attributed to the increase in the turbidity of suspension due to more suspended photocatalyst solids. The light scattering by the catalyst particles leads to the blockage of photon absorption. Moreover, less OH radicals can be created [1, 2].
\nIn the acidic pH, the effectiveness of the dye photocatalytic degradation over TiO2-AgNP is found to be low. The photodegradation improves as pH increasing, but when the pH is increased further the photodegradation declines. For methyl orange photodegradation, the optimum pH is reached at 3 [68]. The dye degradation over heterogeneous photocatalyst of TiO2 is initiated by adsorption on photocatalyst surface, leading to sequentially or simultaneously dye degradation. The effectiveness of the adsorption and degradation of dye depends on the surface charge of the catalyst and solution pH. The pH is an effective parameter to affect the surface state [68, 74]. The amphoteric characteristics of synthesized oxides influence the surface charge of the photocatalyst. The pH of dye solution varies with the surface charge of the photocatalyst and shifts the position of redox reaction [68, 74]. Based on the amphoteric characteristics of TiO2, the following equilibriums take place:
\nConcerning the reactions (4) and (5), it is evident that the surface of the photocatalyst can become positively charged in acidic medium and negatively charged in alkaline medium. On the other side, methyl orange in the aqueous medium is in the anionic state that can also affect the adsorption.
\nAt pH lower than 3, the H+ ions cause the dye to become positively charged. Note that the surface of the catalyst is also positive. Since both dye and photocatalyst are positively charged, it will inhibit adsorption and photodegradation. At pH 3, the dye becomes anionic, while the photocatalyst surface is still positively charged. It facilitates better electrostatic attraction between dye molecules and positively charged photocatalyst surface, which speeds up the photodegradation. At pH greater than 7, the surface of the photocatalyst has become negatively charged, which leads to electrostatic repulsion between methyl orange and photocatalyst. Therefore, it results in a decrease in the dye photodegradation efficiency [68].
\nDifferent from the anionic dye, a cationic dye such as methylene blue shows the maximum adsorption and photodegradation at neutral to basic pH. At low pH, the photodegradation may occur less efficient due to electrostatic repulsion between methylene blue molecules and photocatalyst, since both dye molecules and photocatalyst have positive charges. The electrostatic repulsion can inhibit adsorption that results in a decline in the dye degradation. In neutral pH, the dye species is positively charged, whereas photocatalyst is neutral so that they create electrostatic interaction. At higher pH, the dye is neutral, whereas the photocatalyst is in the anionic state, which facilitates efficient adsorption and photodegradation [68]. The maximum photodegradation for this dye takes place at pH 9 [74].
\nIt is apparent that the dye photodegradation reduces gradually when dye concentration improves [66, 75]. At low dye concentration, a few dye molecules in solution can move freely into the active surface of the photocatalyst. When the abundant active sites of the photocatalyst are available to absorb the dye, the dye photodegradation becomes efficient. High dye concentration gives more dye molecules that hinder their movement close to the photocatalyst. Therefore, the adsorption and the photodegradation decrease. For the photocatalyst, the surface has been occupied by much dye that diminishes the active sites at the surface. It leads to less dye adsorption and declines photodegradation [66, 74, 75].
\nThe UV light irradiation time can represent: (1) how long the photocatalyst contact with irradiating light, for further formation of OH radicals and (2) how long the contact between dye with OH radicals to proceed photodegradation. A general trend shows that the extension of the irradiation time enhances photodegradation, but the photodegradation stays constant or even decreases slightly for extended irradiation. Long UV light exposure produces more OH radicals, which helps the photodegradation take place more efficiently. However, further addition of irradiation time leads to surface saturation of the photocatalyst to release OH radicals [66, 75].
\nFollowing the initial description of the physiologically corrective operation for tricuspid atresia by Fontan and Baudet [1] and Kreutzer and his associates [2] almost simultaneously, such surgery was widely adapted by most pediatric cardiologists and pediatric cardiac surgeons. This concept of bypassing the right ventricle (RV) was further extended to manage other cardiac defects with a functionally single ventricle.
The original surgery as described by Fontan and Baudet [1] consisted of (1) end-to-end anastomosis of superior vena cava (SVC) with the right pulmonary artery (PA) (classical Glenn procedure [3]), (2) connection of the separated right PA to the right atrium (RA) either directly or through an aortic homograft, (3) closure of the defect in the atrial septum, (4) insertion of a pulmonary valve homograft into the orifice of the inferior vena cava (IVC), and (5) ligation of the main PA, to entirely bypass the RV. On the basis of the procedures performed, one must infer that Fontan’s concept was to use the right atrium as a pumping chamber; therefore, he inserted a prosthetic valve into the IVC and right atrial-pulmonary artery junction.
On the contrary, Kreutzer et al. [2] anastomosed the right atrial appendage to the PA directly or by a pulmonary homograft and closed the ASD. Neither a Glenn procedure was performed nor a prosthetic valve was inserted in the IVC. Kreutzer’s view appears to be that the RA does not function as a pump and that the left ventricle functions as a suction pump in the system.
The surgical procedure as generally performed appears to shadow Kreutzer’s principle, and consequently, I have used the term “Fontan-Kreutzer operation” to describe this procedure [4, 5, 6, 7, 8]. However, because of priority of publication and more common usage in the literature, I will use the term “Fontan operation” in this chapter.
In this review, I will discuss the evolution of the Fontan concepts, the indications for Fontan operation, the Fontan procedure as used currently, and the results of old and current types of Fontan.
A number of modifications of the aforementioned surgery were made by these [1, 2] and other groups of investigators [9, 10] in the field. In this section, these concepts/procedures will be reviewed.
During the first 20 years after Fontan’s [1] and Kruetzer’s [2] description of the procedure, a number of modifications of the surgery were undertaken by several surgeons, as extensively reviewed and referenced elsewhere [9, 10]. In general, there was a consensus that there is no need for a classic Glenn anastomosis and that a prosthetic valve is not necessary in the IVC. Detailed review of these papers revealed that four major types of Fontan operations were being performed for physiologic correction of tricuspid atresia. These include (1) RA-PA anastomosis, direct or through a non-valved conduit; (2) RA-PA anastomosis through a valved conduit; (3) RA-RV anastomosis, direct or non-valved anastomosis; and (4) RA-RV anastomosis through a valved conduit.
In order to understand the advantages of one operation over the other, 17 papers published as of December 1990 that have documented adequate information to evaluate mortality and reoperation rates for each of the four types of Fontan surgery were reviewed. Pooled data from these 17 articles and statistical comparisons were presented in Tables I–IV for the interested reader [9]. This analysis revealed that atriopulmonary (RA-PA) connection appears to be better than atrioventricular (RA-RV) anastomosis and direct connection is better than valved or non-valved conduit anastomosis. Nevertheless, atrioventricular valved (homograft) conduit anastomosis appears to have advantages of (1) restoring a four-valved, four-chambered, biventricular heart and (2) lower right atrial pressure than with atriopulmonary connection. Based on these data [9, 10], the following conclusions were drawn: (1) direct atriopulmonary connection for children with tricuspid atresia with normally related great arteries and a small (<30% of normal) right ventricle without trabecular right ventricular component and for patients who had tricuspid atresia with transposition of the great arteries and (2) atrioventricular valved (homograft) conduit anastomosis for patients with tricuspid atresia and normally related great arteries but with a right ventricular size greater than 30% of normal and a trabecular right ventricular component [9, 10].
Bidirectional cavopulmonary anastomosis is a modified version of classic Glenn procedure in which the upper end of the divided SVC is anastomosed end to side to the right PA without disconnecting the latter from the main PA. Thus, the SVC blood is diverted into both the right and left PAs, justifying the term, “bidirectional.”
Experimental bidirectional cavopulmonary anastomosis was first studied by Haller et al. [11] in animal models, and its first clinical use was described by Azzolina et al. [12] in 1972. Other investigators [13, 14, 15, 16, 17] later applied this technique to palliate complex heart defects with decreased pulmonary blood flow. Hemodynamic advantages of the bidirectional Glenn procedure are improvement of effective pulmonary blood flow, decrease in total pulmonary blood flow, and reduction of left ventricular volume overloading. In addition, preservation of continuity of the pulmonary artery is an added advantage and may help facilitate a low-risk Fontan procedure. When both right and left SVCs are present, bilateral bidirectional Glenn shunts should be performed, especially if the bridging innominate vein is absent or small. Based on our own experience and that published in the literature [13, 14, 15, 16, 17], the author recommended serious consideration in employing bidirectional cavopulmonary anastomosis as an interim palliative procedure for patients who are at an increased risk for the Fontan procedure [9, 10].
Puga et al. [18] positioned a patch inside the right atrium to divert the IVC blood into the PAs; they had good results in the 12 patients that they used this technique. This was later called lateral tunnel and was widely used until extra-cardiac conduits came into vogue.
To better understand the valve-less atriopulmonary anastomosis type of Fontan, de Leval et al. [19] performed hydrodynamic studies and found that (1) the right atrium is not an efficient pump in non-valved atriopulmonary connections, (2) pulsations in a non-valved circulation truly generate turbulence with consequent decrease in net flow, and (3) energy losses occur in the non-pulsatile chambers, corners, and obstructions. In an attempt to address these deficiencies, they developed a procedure which they named “total cavopulmonary connection.” In this procedure, they connected the divided SVC, end to side, to the undivided right pulmonary artery (bidirectional Glenn), and the IVC blood is diverted through a composite intra-atrial tunnel (with the use of posterior wall of the right atrium as posterior wall of the tunnel) into the cardiac end of the divided superior vena cava, which in turn was connected to the PA. They felt that technical simplicity, maintenance of low right atrial and coronary sinus pressure, and reduction of risk of atrial thrombus formation are advantages of this type of operation. They performed this procedure on 20 patients and observed two early deaths and one late death. Postoperative hemodynamic studies were performed in 10 of the survivors which indicated good results. They recommended this type of operation for patients with a non-hypertrophied right atrium. While the total cavopulmonary connection was initially devised for patients with complex atrial anatomy and/or systemic venous anomalies, it has since been used extensively for all types of cardiac anatomy with one functioning ventricle and irrespective of venous anomalies.
Subsequent experimental studies by Sharma and his associates [20] indicated that complete or minimal offset between the orifices of the SVC and IVC into the right pulmonary artery decreases energy losses.
Marcelletti et al. [21, 22] used an interposition extra-cardiac conduit from the IVC to the PA in place of lateral tunnel used in total cavopulmonary connection in 1990. Subsequently, most surgeons adopted this modification of total cavopulmonary connection, and currently extra-cardiac conduits are used in most Fontan operations.
Since the vast majority of patients requiring Fontan operation present as neonates or in the early infancy, palliative procedures are performed at the time of presentation, and subsequently (at 12–18 months of age) the Fontan operation is undertaken. A considerable mortality (~16%) was seen with primary Fontan surgery, largely related to the impact of rapid changes in ventricular geometry and development of ventricular diastolic dysfunction. The concept of further staging the procedure by performing bidirectional Glenn procedure around 6 months of age followed by final Fontan between 12 and 18 months of age was introduced in early 1990s [23, 24]. Performing the Fontan procedure in stages appears to decrease overall mortality, most likely related to improving the ventricular function by correction of the afterload mismatch that is associated with one-stage Fontan procedure. At the current time, most centers prefer staged Fontan with bidirectional Glenn initially, followed later by extra-cardiac conduit diversion of the inferior vena caval blood into the PA.
In 1978, Choussat et al. proposed several criteria for performing Fontan operation [25]. Many cardiologists and surgeons have modified these criteria. Patients not meeting these criteria were deemed to be at a higher risk for a poor prognosis following a Fontan operation than patients who are within the limits of the set criteria. For the high-risk group, several investigators have proposed the concept of leaving a small atrial septal defect (ASD) open to facilitate decompression of the right atrium [26, 27, 28]. Laks et al. advocated closure of the atrial defect by constricting the preplaced suture in the postoperative period [28], while Bridges et al. [27] used a transcatheter closure method at a later date.
Higher cardiac output and significant decreases in the postoperative pleural effusions and systemic venous congestion were noted after a fenestrated Fontan procedure. In addition, the duration of hospitalization appears to have decreased. Nonetheless, these beneficial effects are at the expense of mild arterial hypoxemia and potential for paradoxical embolism.
While the fenestrated Fontan procedure was initially designed for patients at high risk for Fontan surgery, it has since been used in patients with modest or even low risk. Although rare, reports of cerebrovascular or other systemic arterial embolic events occurring after a fenestrated Fontan operation tend to contraindicate the use of fenestrations in patients with low or usual risk. In following years, fenestrated Fontan have been routinely used at most institutions. Some data indicate that routine fenestration is not necessary [29].
Patients who have undergone a fenestrated Fontan operation or patients who have a residual atrial defect, despite correction, may have clinically significant right-to-left shunt causing varying degrees of hypoxemia. These residual defects should be closed not only to address arterial desaturation but also for prevention of paradoxical embolism [30, 31]. Although two types of fenestration closure, namely, constriction of the preplaced suture in the postoperative period [26, 28] and device closure later [27] were described, device closure is opted at most institutions. Closure of such defects can be performed by using transcatheter techniques [32, 33, 34, 35]. The procedure is usually performed 6–12 months following fenestrated Fontan procedure. Although a number of devices have been used in the past [32, 33, 34, 35], at the present time, Amplatzer septal occluders are the most commonly used devices to accomplish such closures.
The indications for opting for a Fontan operation are patients who have one functioning ventricle. At first, patients with tricuspid atresia were selected for this procedure [1, 2]. Shortly thereafter, patients with double-inlet left (single) ventricle were added to the indications for Fontan [36]. Following description of surgical palliation of hypoplastic left heart syndrome (HLHS) by Norwood et al. [37, 38] in the early 1980s, HLHS became the major lesion requiring Fontan operation. Subsequently, mitral atresia (with normal aortic root), unbalanced atrioventricular septal defects (AVSDs), pulmonary atresia with intact ventricular septum with markedly hypoplastic right ventricle, and other complex heart defects with one functioning ventricle were selected for Fontan surgery.
Attempts to insert prosthetic ventricular septum for single ventricle patients met with problems, leading to abandoning such procedures. Thereafter, Fontan became a preferred treatment method. With reasonably good results of Fontan, the pendulum swung so that any patient who could not undergo complete repair became a candidate for Fontan.
A middle of the road method, the so-called one-and-one-half ventricle repair was developed for patients with pulmonary atresia with intact ventricular septum with modest-sized right ventricle. In this procedure, a bidirectional Glenn procedure to divert the SVC flow into the PA is performed and allows the small right ventricle to pump the IVC blood into the pulmonary circuit, and the patent foramen ovale is closed. It is generally considered to be a better option than Fontan, although, to my knowledge, there are no comparative studies to assess this issue.
Because of relatively high mortality rates (17.0–31.7%) [39, 40] and low actuarial survival rates (66.5% at 5 years and 64.4% at 15 years) [41] for unbalanced AVSD patients following Fontan, a number of institutions attempted single stage or staged biventricular repair or conversion from single ventricle (Fontan) to biventricular repair [39, 42, 43, 44, 45, 46, 47]. Detailed analysis by Nathan et al. [39] suggested that the biventricular repair and conversion from single ventricle (Fontan) to biventricular repair groups had reasonably similar mortality rates and a similar need for cardiac transplantation, but these parameters were lower than those seen in the Fontan palliation cohort.
Cardiac transplantation is a surgical alternative in the management of HLHS [48] and other single ventricle lesions. While heart transplantation was used at several institutions initially for HLHS, because of non-availability of donor hearts, most institutions have reverted to the Norwood/Fontan route. In addition, following successful cardiac transplantation, multiple medications for the prevention of graft rejection, frequent outpatient visits and periodic endomyocardial biopsy, to recognize rejection very early, are necessary in the management of these children. At the present time, cardiac transplantation is used for patients failing Fontan operation at a limited number of institutions.
As reviewed above, since the original description in the early 1970s, the Fontan procedure has undergone numerous modifications, and, at the present time it is best described as staged total cavopulmonary connection (TCPC) with an extra-cardiac conduit and fenestration. It is performed in three stages.
The majority, if not all, of patients who require Fontan operation (see Section 3. Indications for Fontan Operation) present during the neonatal and early infancy period, and the Fontan cannot be performed at that time because of naturally high PA pressure and high pulmonary vascular resistance (PVR). Therefore, Fontan, by necessity, becomes a multistage procedure. These babies should receive palliative intervention to allow them to reach the age and size to undergo successful Fontan surgery. The type of palliation is largely dependent upon the hemodynamic disturbance produced by multiple defects associated with a given congenital heart defect (CHD).
In neonates with decreased pulmonary blood flow, the ductus arteriosus should be kept open by administration of prostaglandin E1 (PGE1) intravenously at a dose of 0.05–0.1 mcg/kg/min. Once the O2 saturation improves, the dosage of PGE1 is gradually reduced to 0.02–0.025 mcg/kg/min to minimize the side effects of the prostaglandins. Following stabilization and diagnostic studies, as necessary to confirm the diagnosis, a more permanent way of providing pulmonary blood flow should be instituted. A number of methods to augment pulmonary blood flow have been used over the years [49, 50]. These include subclavian artery to ipsilateral PA anastomosis (classic Blalock-Taussig shunt), descending aorta to the left PA anastomosis (Potts shunt), ascending aorta to the right PA anastomosis (Waterston-Cooley shunt), SVC to right PA anastomosis, end-to-end (classic Glenn shunt), enlargement of the ventricular septal defect (VSD), formalin infiltration of the wall of the ductus arteriosus, central aortopulmonary fenestration or expanded polytetrafluoroethylene (Gore-Tex; W. L. Gore and Associates, Inc., Newark, Delaware) shunt, Gore-Tex interposition graft between the subclavian artery and the ipsilateral PA (modified Blalock-Taussig shunt), balloon pulmonary valvuloplasty, and stent implantation into the ductus arteriosus. Currently modified Blalock-Taussig (BT) shunt [51] by insertion of a Gore-Tex graft between the subclavian artery to the ipsilateral PA (Figure 1a) is performed by most surgeons to address pulmonary oligemia. More recently connecting the RV outflow tract with the PA via non-valve Gore-Tex graft is being used at several institutions to palliate pulmonary oligemia. Placement of a stent in the ductus arteriosus [52, 53, 54] and balloon pulmonary valvuloplasty (if the predominant obstruction is at the pulmonary valve level) [55, 56, 57] are other available options to augment the pulmonary blood flow.
Stage I Fontan. Selected frames form cineangiograms in two different babies; the first with pulmonary oligemia who received Blalock-Taussig (BT) shunt (a) and the second with pulmonary plethora who had pulmonary artery banding (PB) (b). C, catheter; LPA, left pulmonary artery; RPA, right pulmonary artery (Reproduced from [30]).
In babies with increased pulmonary blood flow, optimal anti-congestive measures should be started immediately. Once the congestive heart failure (CHF) is adequately addressed, PA banding (Figure 1b) is performed [58] irrespective of control of CHF.
Infants with near normal pulmonary blood flow with O2 saturations in the low 80s do not need intervention and are clinically followed until Stage II.
Neonates with hypoplastic left heart syndrome usually have Norwood palliation (Figure 2) [37, 59] in the neonatal period; in this operation, the following procedures are performed: (1) the main pulmonary artery and the aorta are anastomosed together; additional prosthetic material is used as needed; (2) the pulmonary circulation receives blood supply by connecting the aorta to the PA via a modified BT shunt [51] (Figure 2b); (3) atrial septum is excised to allow unhindered blood flow from the left to the atrium; and (4) ductal tissue is removed, and coarctation of the aorta, if present is repaired. Some surgeons use alternative Sano shunt [60], connecting the RV outflow tract to the PA (Figure 2c) instead of BT shunt.
Stage I Fontan for hypoplastic left heart syndrome. Selected frames from cineangiograms demonstrating Norwood operation in which the neoaorta (NAo) and hypoplastic aorta (HAo) perfuse the coronary arteries (CAs) as shown in (a), Blalock-Taussig (BT) shunt as illustrated in (b) and Sano shunt as depicted in (c). (b) and (c) are from two different babies. LPA, left pulmonary artery; RPA, right pulmonary artery (Reproduced from [30]).
In patients with inter-atrial obstruction, it should be relieved either by transcatheter methodology or by surgery as deemed appropriate for a given clinical scenario. If there is associated coarctation of the aorta, it should also be relieved. Some patients with double-inlet left ventricle may have significant obstruction at the level of bulboventricular foramen [61]. Similarly some babies with tricuspid atresia with transposition of the great arteries may have obstruction at the VSD level, causing obstruction to systemic blood flow [61, 62]. Such babies require Damus-Kaye-Stansel (connection of the aorta to the PA) [63] along with a BT shunt. Inter-atrial obstruction may be present frequently in babies with mitral atresia and single ventricle [64]. In such babies, predictable fall in PVR occurs following balloon or surgical relief of inter-atrial obstruction [64]; consequently, PA banding should be undertaken without hesitation at the time of relieving the atrial septal obstruction, so as to reduce the probability for CHF, lower the PVR and PA pressure, prevent pulmonary vascular obstructive disease (PVOD), and pave the way for Fontan approach [64].
Irrespective of the type of palliative surgery in the neonatal period, bidirectional Glenn procedure [12, 13, 14, 17, 23], namely, anastomosis of the SVC to the right PA, end-to-side (Figure 3) is performed around the age of 6 months. The previously performed BT or Sano shunt is ligated at the same time. Although performing the procedure at 6 months is generally adopted, it can be performed as early as 3 months provided normalcy of PA pressure and anatomy can be documented.
Stage II of Fontan. Selected frames from cineangiograms in two different children illustrating bidirectional Glenn operation in which the superior vena cava is anastomosed to the right pulmonary artery (RPA). Unobstructed flow from the SVC to the right (RPA) and left (LPA) pulmonary arteries is clearly seen. (Reproduced from [30]).
In patients with persistent left SVC, bilateral bidirectional Glenn (Figure 4) is undertaken especially in patients with a small or absent left innominate vein. A bidirectional Glenn procedure may also be performed for patients with infrahepatic interruption of the IVC with azygos or hemiazygos continuation, and such a procedure is called a Kawashima procedure by some authorities.
Stage II Fontan. Selected frames from cineangiograms in a different child than shown in Figure 3, illustrating bilateral bidirectional Glenn operation. (a) Superior vena caval angiogram demonstrates immediate visualization of the right pulmonary artery (RPA). Un-opacified blood flow from persistent left SVC (PLSVC) is indicated by the arrow in (a). (b) PLSVC angiogram illustrates rapid opacification of the left pulmonary artery (LPA). Un-opacified blood from the right SVC is shown by the arrow in (b). Flow from the respective SVCs into the pulmonary arteries is clearly seen (Reproduced from [30]).
Prior to the bidirectional Glenn procedure, normal PA pressures and adequate size of the branch PAs should be ensured by cardiac catheterization and cineangiography. Echo-Doppler or other imaging studies (magnetic resonance imaging [MRI] or computed tomography [CT]) is advocated at some institutions.
If PA stenosis is present, it may be addressed with balloon angioplasty or stent implantation, as deemed appropriate, or it may be addressed during the bidirectional Glenn procedure. Atrioventricular valve regurgitation, aortic coarctation, subaortic obstruction, and other abnormalities should also be repaired/addressed at the time of this operation.
During the final Stage III, the IVC flow is diverted into the PA along with creation of a fenestration. We arbitrarily divided [30] these procedures into Stage IIIA (diversion of IVC into the PA) and Stage IIIB (closure of the fenestration).
In the final Stage III, the total cavopulmonary connection is achieved by diverting the IVC flow into the PA either by a lateral tunnel [18, 65] or by an extra-cardiac, non-valved conduit (Figures 5 and 6) [21, 22]; the procedure is usually performed between the ages of 1 and 2 years, usually 1 year following the bidirectional Glenn procedure. Most surgeons seem to prefer extra-cardiac conduit to accomplish this final stage of Fontan. The majority of surgeons construct a fenestration, 4–6 mm in size, between the conduit and the atria (Figures 5 and 6) [27]. While the creation of fenestration during the Fontan operation was initially proposed for high-risk patients [27, 28], most surgeons now seem to prefer fenestration, since fenestration during the Fontan improves mortality rate and reduces morbidity during the immediate postoperative period [30].
Selected cine frames in posteroanterior (a) and lateral (b) views, demonstrating Stage IIIA Fontan procedure diverting the inferior vena caval flow into the pulmonary arteries via a non-valve conduit (Cond). Flow across the fenestration (fen) is shown by arrows in (a) and (b). HV, hepatic veins; LPA, left pulmonary artery; PG, pigtail catheter in the descending aorta; RPA, right pulmonary artery.
Selected cine frames in posteroanterior (a) and lateral (b) views in a different patient to the one shown in Figure 5, demonstrating Stage IIIA Fontan procedure diverting the inferior vena caval (IVC) flow into the pulmonary arteries via a non-valve conduit (Cond). Flow across the fenestration (fen) is shown by arrows in (a) and (b). Abbreviations are the same as those in Figure 5.
Cardiac catheterization and selective cineangiography are usually performed shortly prior to Fontan conversion in order to assess the PA anatomy and pressures, trans-pulmonary gradient, PVR, and ventricular end-diastolic pressure and to assure that they are normal prior to proceeding with Fontan completion. At some institutions, MRI is used for this assessment instead of catheterization and angiography; however, the author’s preference is catheterization. During this catheterization, any significant collateral vessels that are present are also transcatheter-occluded by most cardiologists.
In the final stage, Stage IIIB, the fenestration is closed (Figures 7b, 8b, and 9B and C) by transcatheter methodology [27, 30, 31, 32, 33, 34, 35], usually 6–12 months after Fontan Stage, IIIA. In the past, most devices used to occlude ASDs [32, 33, 34, 35] were employed for this purpose, but at the present time, Amplatzer septal occluders are the most commonly used devices to accomplish such closures. If there are any other residual shunts, they should also be occluded (Figure 10) by device closure.
Stage IIIB. (a) Selected frames from cineangiograms in anteroposterior projection illustrating Stage IIIA of the Fontan operation in which the inferior vena caval (IVC) flow is diverted into the pulmonary arteries by a non-valve conduit (Cond). The fenestration (fen) is shown by the arrow in (a). (b) Closure of the fenestration with an Amplatzer septal occluder device (D) is shown with an arrow in (b). HV, hepatic veins; LPA, left pulmonary artery; RPA, right pulmonary artery (Reproduced from [30]).
Stage IIIB. (a) Selected frames from cineangiograms in lateral view of the same patient illustrated in Figure 5 showing Stage IIIA of the Fontan operation in which the inferior vena caval (IVC) flow is diverted into the pulmonary arteries by a non-valve conduit (Cond). The fenestration (fen) is shown by the arrow in (a). (b) Closure of the fenestration with an Amplatzer septal occluder device (D) is shown with an arrow in (b). (Stage IIIB). Reproduced from [30].
(A) Selected cine frame from a Fontan conduit cineangiogram in anteroposterior view, demonstrating tubular fenestration (Tu fen) with opacification of the left atrium (LA). (B) The Tu fen is closed with an Amplatzer vascular plug (AVP). (C) A follow-up conduit cineangiogram after AVP implantation, showing complete occlusion of the Tu fen. TEE, transesophageal probe.
(A) A selected cineangiographic frame showing the Fontan conduit in lateral view, demonstrating a residual shunt (RS) at the superior aspect of the conduit (Cond). (B) The RS was occluded with an Amplatzer septal occluder device (AD); the residual shunt is no longer seen. TEE, transesophageal echo probe.
In children who have one functioning ventricle requiring Fontan correction, the systemic and pulmonary circulations work in-parallel in place of the usual in-series circulation. A fragile equilibrium between the two circulations must be preserved so that adequate systemic and pulmonary perfusions are maintained. There is substantial interstage mortality ranging from 5 to 15% [66, 67, 68] which may be due to restrictive atrial communication, obstruction of the aortic arch, blockage of the shunt, distortion of the PAs, atrioventricular valve insufficiency, or a combination thereof [66]. Intercurrent illnesses such as dehydration, respiratory tract illness, or fever disturb this balance and make the patients to become critically ill and have been blamed for interstage mortality [66, 68]. The surgically created BT and Sano shunts may also get thrombosed producing severe hypoxemia [69]. Indeed, these abnormalities produce significant interstage mortality [67]; these appear to occur more frequently between Stages I and II than between Stages II and III. Consequently, extreme vigilance in managing these patients should be maintained by the caregiver [68, 70]; even trivial illnesses must be aggressively monitored and addressed as appropriate.
Immediate and follow-up results of both older and current types of Fontan will be reviewed in this section.
The results of original Fontan [1, 2] and its earlier modifications, namely, RA-to-PA or RA-to-RV anastomosis either directly or via valved or non-valved conduits, revealed high initial mortality rates. The initial mortality rates ranged from 10 to 26% [9, 10, 71, 72]. Furthermore, the postoperative stay in the intensive care setting was prolonged.
The initial mortality following staged, total cavopulmonary connection has decreased remarkably [73, 74, 75, 76, 77, 78]. Patients who had total cavopulmonary connection without fenestration had initial mortality rates ranging from 8 to 10.5% [73, 74, 75], while subjects who had total cavopulmonary connection with fenestration had slightly lower (4.5–7.5%) initial mortality rates [76, 77, 78].
In one large single institutional study examining the results of 500 consecutive Fontan surgery patients [77], early failure was associated with high (≥19 mm Hg) mean PA pressure, young age at surgery, heterotaxy syndrome, a right-sided tricuspid valve as systemic atrioventricular valve, distorted pulmonary arteries, an atriopulmonary connection, no Fontan fenestration, and longer cardiopulmonary bypass time.
These investigators also observed that a significant improvement in morbidity and mortality from early (first quartile—early failures: 27.1%) to the more recent time (last quartile—early failures: 7.5%) occurred [77]. This progress appears to be related to increasing surgical and intensive care experience as well as to more recently introduced Fontan modifications.
Long-term follow-up results were also poor with older types of Fontan [9, 10]. The late mortality rates varied from 1 to 11%, and when early and late mortality rates were combined, they varied between 11 and 25%. The need for reoperations was present in 1–11% of patients. Factors adversely influencing late mortality and reoperation rates are earlier calendar year of operation, age of patient at the time of surgery, type of prior palliative procedures, hypoplasia, distortion or obstruction of PAs, subaortic obstruction, significant mitral valve insufficiency, elevated PA pressure or resistance, decreased left ventricular function, increased left ventricular muscle mass, asplenia syndrome, and others [9, 10].
Following the introduction of staged cavopulmonary anastomosis (both lateral tunnel and extra-cardiac conduit diversion of IVC blood to the PA), the long-term outcomes have improved. In one study in which results of follow-up for 10.2 ± 0.6 years of 196 patients were examined, the estimated Kaplan-Meier survival was 93 and 91% at 5 and 10 years, respectively [79]. An equally impressive finding was freedom from supraventricular arrhythmias in 96 and 91% of patients at 5 and 10 years following surgery. In a different study, the actuarial survival 15 years following surgery was 85% [80]. But, late re-interventions were necessary in 12.7% of patients. When lateral tunnel and extra-cardiac conduit types of Fontan were compared, the outcomes were found to be similar for both groups [81, 82].
Using fenestration during Fontan appears to improve early mortality and morbidity, particularly demonstrated in high-risk patents [83]. A more recent analysis in a smaller group of patients did not demonstrate significant advantage of fenestrated Fontan over the non-fenestrated [84]. However, the general consensus is that using fenestration during Fontan decreases mortality and morbidity during the postoperative period [30, 76, 77, 78].
Periodic follow-up following Fontan is generally recommended. These patients are evaluated at 1, 6, and 12 months after Stage IIIB (device closure of fenestration) and yearly thereafter. During the follow-up, platelet-inhibiting doses of aspirin 2–5 mg/kg/day in children or clopidogrel 75 mg/day in adults to prevent thrombus formation and angiotensin-converting enzyme inhibitors for afterload reduction are generally prescribed. Electrocardiograms and echocardiograms are generally performed during evaluation of these patients with additional imaging studies, as indicated. Any abnormalities, as and when detected, are addressed.
During follow-up, a number of complications were reported, and these include arrhythmias, obstructed Fontan pathways, cyanosis, paradoxical emboli, thrombi, development of collateral vessels, and protein loosing enteropathy [30, 31, 85]. These complications appear to be more frequent with older types of Fontan than with the currently used staged, total cavopulmonary connection with extra-cardiac conduit and fenestration. When such complications develop, they should be promptly investigated and treated. In the ensuing paragraphs, a brief review of some of these complications will be presented.
Arrhythmias were more frequently seen in patients with old Fontan (atriopulmonary connection) than with staged TCPC. The observed arrhythmias were typically atrial arrhythmias, namely, atrial flutter/fibrillation and supraventricular tachycardia. Initially, anti-arrhythmic medications are used to control the rhythm disturbance. This should be followed by hemodynamic and angiographic assessment to identify obstructive lesions in the Fontan pathways. The obstructive lesions should be treated with balloon angioplasty, stent, or surgery, as applicable. Continued rhythm abnormality calls for radiofrequency ablation. Although the success rate of radiofrequency ablation is high in 80% range [86], rates of recurrence range from 30 to 40%. In subjects who have resistant arrhythmias, reducing the atrial mass, switch to TCPC with concomitant Maize procedure is advisable [87]. A few patients develop atrioventricular block or sick sinus syndrome which may require pacemaker implantation. Fortunately, ventricular arrhythmias are less frequent.
Obstructions in Fontan circulation may occur. Obstructive lesions in the SVC or IVC may arise but are less frequently seen. However, branch pulmonary artery stenoses may be seen more often. Obstructions within the lateral tunnel or extra-cardiac conduit are also uncommon, but may occur due to thrombus formation and will be addressed in the section on “Thrombus formation.” In the presence of signs and symptoms indicative of obstruction in the Fontan pathway, prompt investigation to confirm such obstruction should be made. While echo studies are useful in young children, poor echo windows in adolescents and adults may require MRI and CT, and/or angiographic studies to confirm or exclude such obstructive lesions. If the obstructive lesions are detected, they should be promptly relieved by balloon angioplasty or stent implantation (Figure 11) [88]. Surgery may be needed in rare occasions.
Selected frames from cineangiograms of the pulmonary artery in posteroanterior view illustrating normal right pulmonary artery (RPA) and narrowed (arrow) left pulmonary artery (LPA) prior to (a) and after (b) stent (arrow) placement in an adolescent who had Fontan surgery several years earlier (Reproduced from [88]).
Sometimes connections between lateral tunnel and extra-cardiac conduit on the one hand and the atrium on the other persist. These residual defects and intentionally created Fontan fenestrations result in right-to-left shunt because the pressure in the Fontan conduit is higher than that of the atrial pressures. These residual defects will result in arterial desaturation and may become the site of paradoxical embolism with consequential transient ischemic attacks (TIAs), cerebrovascular accidents (CVAs), and systemic emboli. These residual defects as well as Fontan fenestrations should be occluded by transcatheter techniques to return O2 saturations to normal and decrease the likelihood for paradoxical embolism [30, 32, 33, 83, 88, 89]. Amplatzer septal occluder (St. Jude Medical, Inc., St Paul, MN) is currently most common device used to accomplish this (Figures 7,8, and 10). Tubular fenestrations may be closed with Amplatzer vascular plug devices (St. Jude Medical, Inc.) (Figure 9). Test occlusion of the residual defect or fenestration is suggested to ensure that adequate cardiac output is maintained following defect occlusion [89, 90], especially if the procedure is performed shortly after fenestrated Fontan. Late follow-up results of fenestration closure are good [33].
There is a tendency for thrombus formation in the Fontan pathway; the reported prevalence was 15–30% [91, 92]. Regrettably the usual transthoracic echo-Doppler evaluation may not discover these thrombi. However, transesophageal echocardiography, MRI, or CT studies may be necessary to detect these thrombi. In an attempt to prevent thrombus formation in the Fontan circuit, thromboprophylaxis is commonly recommended; both warfarin and aspirin have been utilized in the past for this purpose. A multicenter, randomized trial was conducted to compare the efficacy of these two drugs; results showed less than optimal results with both drugs and no significant difference between the two regimens [93]. In the author’s experience, most children are prescribed with aspirin for thromboprophylaxis which may be switched to clopidogrel (Plavix) as the children approach adulthood.
Despite seemingly adequate thromboprophylaxis, some patients develop thrombosis of the Fontan conduits (Figure 12A). We initially employ thrombus dissolving drug therapy (tPA, heparin, etc.). If the thrombi do not resolve, we have employed stenting of the conduit to compress the thrombi against the conduit wall [94]. An example from our experience is shown in Figure 12.
(A) Selected frame from a cineangiogram of a Fontan conduit in lateral view, illustrating a thrombus (arrow in (A)). (B) and (C) position of a stent (St) before (B) and after (C) its complete expansion. (D) Cineangiographic frame demonstrating the widely patent stent after stent deployment. Also, note the residual shunt (RS) at the superior aspect of the conduit (seen in (A) and (D)). The RS was occluded with an Amplatzer septal occluder device (AD) shortly after the cine shown in (D). (F) A follow-up cineangiogram 1 year later shows the continued patency of the conduit with no RS. TEE, transesophageal echo probe (Reproduced from [94]).
Systemic venous to pulmonary venous and systemic arterial to pulmonary arterial collateral vessels may develop in some patients after the Fontan procedure [88, 95]. These may develop both shortly after the procedure and during late follow-up. Systemic venous to pulmonary venous collateral vessels produce arterial hypoxemia. In addition, they may also become potential sites for paradoxical embolism. Systemic arterial to pulmonary arterial (or venous) collateral vessels produce left ventricular volume overload. These abnormal vessels should be transcatheter-occluded with coils, vascular plugs, and ductal occluding devices depending upon the size and accessibility. Examples from the author’s experience of occluding these vessels are shown in Figures 13–16 [88, 95, 96].
(a) Selected frame from a left innominate vein (L inn) cineangiogram in posteroanterior view demonstrating an anomalous vein (AV) opacifying the atrial mass (not marked). (b) Following occlusion with Gianturco coil (arrow), the AV is completely occluded and the systemic arterial saturation improved (Reproduced from [88]).
(A) Selected frame from a cineangiogram in lateral view with the catheter positioned at the superior vena cava/azygos junction illustrating a fistula which results in opacification of the left atrium (LA). (B) The fistula was occluded with an Amplatzer vascular plug (arrow—AVP) with some residual flow. (C) Follow-up SVC injection shows complete occlusion by the AVP (Reproduced from [96]).
(A) Selected cine frame from an internal mammary artery (IMA) cineangiogram in the lateral view, demonstrating multiple small collateral vessels arising from the pericardiophrenic (PCP) branch, which resulted in a significant levophase (not shown). (B) Following occlusion with a Gianturco coil (C), there is complete occlusion of this vessel (Reproduced from [95]).
(A) Selected cine frame from a right subclavian artery (RSA) cineangiogram showing branches (white arrows) of the thyrocervical (TC) trunk which supplied a number of small vessels, giving a good degree of levophase. (B) Complete occlusion occurred following the implantation of a Gianturco coil (C) (Reproduced from [95]).
Protein losing enteropathy (PLE) is a grave long-term complication of Fontan with a prevalence of 11.1% in older types of Fontan [85, 97]. However, the incidence appears to have come down to 1.2% with staged TCPC [85, 98]. The reason for development of PLE is not understood. Intestinal protein loss secondary to lymphatic distension which in turn may be due to elevated pressure in systemic veins is considered to be a pathogenic mechanism. But, PLE has been seen even in patients with “normal” Fontan circuit pressures. Therefore, the true cause of PLE remains a mystery. The symptoms and signs of PLE are diarrhea, edema, ascites, and/or pleural effusions. Laboratory abnormalities include reduced serum albumin and elevated fecal alpha-1 antitrypsin levels. The PLE diagnosis may be confirmed with technetium 99m-labeled human serum albumin scintigraphy [99].
Because of high mortality rate seen with PLE, speedy diagnosis and implementing aggressive management strategies are important [85]. At first, supportive therapy such as medium-chain triglycerides diet, infusion of intravenous albumin, and replacement of immunoglobulins should be undertaken. Obstructive lesions in the Fontan pathway should be scrutinized, and aortopulmonary connections should be screened for. If identified, they should be treated with appropriate transcatheter measures. Surgical therapy is indicated if they cannot be adequately addressed with transcatheter intervention. A variety of other treatment regimens, including prednisone, elementary diet, calcium replacement, regular high-molecular-weight heparin, low-molecular-weight heparin, somatostatin, high-dose spironolactone, sildenafil, and resection of localized intestinal lymphangiectasia, have been utilized in the past with varying degrees of success [85].
Following a short trial of any of the above treatment modes, largely on the basis of the cardiologist’s preference, a more definitive treatment methods such as lessening the conduit pressure by creating a fenestration between the conduit and the atrium [99, 100, 101], converting atriopulmonary type of Fontan to TCPC [87, 102, 103], instituting sequential atrioventricular pacing [104, 105], and performing cardiac transplantation [106, 107, 108] should all be considered. Again, it is essential to emphasize that timely treatment should be instituted as soon as PLE is identified [85]. Fortunately, the need for use of these methods has progressively diminished since the wide use of staged TCPC.
Since the initial description of the Fontan operation in the early 1970s by Fontan, Kruetzer, and their associates, several modifications have been introduced. These include avoiding classic Glenn anastomosis; not using a prosthetic valve in the IVC; RA-PA anastomosis, direct or through a non-valved conduit; RA-PA anastomosis through a valved conduit; RA-RV anastomosis, direct or non-valved anastomosis; RA-RV anastomosis through a valved conduit; bidirectional Glenn procedure (cavopulmonary anastomosis); lateral tunnel; total cavopulmonary connection; extra-cardiac conduit, staged Fontan; fenestrated Fontan; and closure of Fontan fenestration. Currently staged, total cavopulmonary connection with extra-cardiac conduit and fenestration has become the most commonly used multistage surgery in accomplishing the Fontan.
The indications for Fontan are patients who have one functioning ventricle, and these include tricuspid atresia, double-inlet left ventricle, HLHS, mitral atresia with normal aortic root, unbalanced AVSDs, pulmonary atresia with intact ventricular septum with markedly hypoplastic right ventricle, and other complex heart defects with one functioning ventricle. Recently there has been a trend for biventricular repair, particularly for patients with unbalanced AVSDs.
Stage I consists of performing palliative procedures on the basis of pathophysiology of the defect complex at presentation, usually in the neonatal period. Stage II involves performing a bidirectional Glenn procedure (diversion of the superior vena caval blood flow into both lungs) usually at about the age of 6 months. During stage IIIA diversion of the IVC blood flow into the lungs, usually by an extra-cardiac conduit plus a fenestration, usually at about the age of 2 years. Stage IIIB consists of transcatheter closure of the fenestration 6–12 months after Stage IIIA.
Both the immediate and follow-up results have remarkably improved, both in terms of mortality and morbidity, following the introduction of staged total cavopulmonary connection with extra-cardiac conduit and fenestration with subsequent catheter closure of Fontan fenestration. Complications do occur during follow-up, and they should be addressed as and when they are detected.
The author declares no conflict of interest.
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