Benutzer:Ssarikouch/Decellularized homografts
Decellularized homografts are donated human heart valves, which have been modified by so called Tissue Engineering methods. Several techniques exist, the majority are based on detergent or enzymatic protocols aiming for elimination of all donor cells while preserving the mechanical properties of the remaining valve structure, the matrix.
Background
[Bearbeiten | Quelltext bearbeiten]Young patients with aortic valve disease today are facing a real dilemma. Once indication for aortic valve replacement has been confirmed by their physician, they have to choose either a mechanical valve replacement option, which directly affects their quality of life as strict life-long blood anticoagulation is needed to avoid cerebral thromboembolism. These “blood thinners” have an inherent risk for severe bleeding episodes, which needs to be considered in both professional and leisure activities. The majority of patients nowadays try to avoid anticoagulation for these reasons. Young patients who do not want mechanical prostheses can opt for a biological prosthesis, e.g. a pericardial heart valve of animal origin (xenogenic), which unfortunately does not provide satisfactory durability in young patients, and rapid valve degeneration can occur within months.[1] These patients further have the option for the so-called Ross procedure which is an extensive operative procedure where a diseased aortic valve is replaced by the patient`s pulmonary valve as an autograft. The pulmonary valve itself has to be consecutively replaced by a heart valve prosthesis leading to a “two-valve” diseased heart, as almost all autografts are impaired by progressive dilatation in the long term and the pulmonary valve prosthesis, often a conventional cryopreserved homograft, degenerates in the same way as all biological valves, thereby leading to frequent reoperations.[2] Reoperations have a substantial higher mortality due to postoperative adhesions.[3]
Tissue engineering concepts
[Bearbeiten | Quelltext bearbeiten]The lack of reasonable heart valve prostheses for young patients has driven research in tissue engineering concepts. Basis for current tissue-engineering concepts are either artificial polymeric or biological scaffolds, which may derive from human tissue donation (allogenic) or animals (xenogenic). Total artificial tissue-engineered heart valve concepts would solve many unmet clinical demands such as permanent availability of different sizes and lengths. These concepts have shown good results in the technical implementation of valved polymeric conduit production and have successfully been used for in vitro and in vivo seeding of different (stem) cell lines. However, long-term animal models have not delivered satisfactory results so far due to the lack of mechanical stability of the total artificial matrices, leading to early failure of valvular function.[4] Tissue-engineered biological scaffolds of porcine origin have failed dramatically in a number of paediatric patients, resulting in cautious scepticism regarding xenogenic matrices.[5]
Conventional homografts
[Bearbeiten | Quelltext bearbeiten]Aortic valve replacement using a homograft was first performed over 50 years ago on the 24th July 1962 by Donald Ross at Guy`s Hospital, London and has been assessed in prospective randomized studies, e.g. in comparison to the Ross-procedure.[6] Aortic valve replacement using conventional cryopreserved homografts to date is performed only in about 3% of all patients, mostly for acute aortic valve endocarditis (see reference 1). Severe calcification of conventional homografts frequently occurs and is the main reason for its restrictive use, however, current guidelines confirm homografts as a valid alternative in young patients with the need for anatomical reconstruction of the outflow tract.
Decellularised aortic homografts (DAH)
[Bearbeiten | Quelltext bearbeiten]Decellularised aortic homografts (DAH) for aortic valve replacement, and decellularised pulmonary valves (DPH) for pulmonary valve replacement have been developed by several groups and companies.
DPH have been clinically implanted since 2002 in pediatric patients and have shown excellent early to midterm clinical performance and have challenged conventional cryopreserved homografts as the “Gold-standard” for pulmonary valve replacement in congenital heart disease.[7]
DAH developed at Hannover Medical School (MHH) provided sufficient mechanical stability for the systemic circulation at the greatest possible extent of antigen elimination and have been validated in long-term animal models.[8] No dilatation has been observed at the different level such as the valve ring plane, in the sinuses or at the level of the sinutubular junction. Haemodynamic performance in terms of effective orifice area of DAH was outstanding compared to all other options. Most interestingly, no calcification of the DAH has been observed to date. In the few cases in which a long valved homograft had to be implanted due to concomitant dilatation of the ascending aorta, there was also no dilatation of the homograft.[9],[10] Auspicious early data led to a European Commission funded prospective clinical trial for further evaluation of this new approach.[11]
References
[Bearbeiten | Quelltext bearbeiten]- ↑ Svensson LG, Adams DH, Bonow RO, Kouchoukos NT, Miller DC, O'Gara PT, Shahian DM, Schaff HV, Akins CW, Bavaria JE, Blackstone EH, David TE, Desai ND, Dewey TM, D'Agostino RS, Gleason TG, Harrington KB, Kodali S, Kapadia S, Leon MB, Lima B, Lytle BW, Mack MJ, Reardon M, Reece TB, Reiss GR, Roselli EE, Smith CR, Thourani VH, Tuzcu EM, Webb J, Williams MR. Aortic valve and ascending aorta guidelines for management and quality measures. Ann Thorac Surg. 2013 Jun;95(6 Suppl):S1-66
- ↑ Sievers HH, Stierle U, Charitos EI, Takkenberg JJ, Hörer J, Lange R, Franke U, Albert M, Gorski A, Leyh RG, Riso A, Sachweh J, Moritz A, Hetzer R, Hemmer W. A multicentre evaluation of the autograft procedure for young patients undergoing aortic valve replacement: update on the German Ross Registry. Eur J Cardiothorac Surg. 2015 Feb [Epub ahead of print]
- ↑ Onorati F et al. Mid-term results of aortic valve surgery in redo scenarios in the current practice: results from the multicentre European RECORD (REdo Cardiac Operation Research Database) initiative. Eur J Cardiothorac Surg. 2014 Mar 30.
- ↑ Emmert MY, Weber B, Behr L, Sammut S, Frauenfelder T, Wolint P, Scherman J, Bettex D, Grünenfelder J, Falk V, Hoerstrup SP. Transcatheter aortic valve implantation using anatomically oriented, marrow stromal cell-based, stented, tissue-engineered heart valves: technical considerations and implications for translational cell-based heart valve concepts. Eur J Cardiothorac Surg. 2014 Jan;45(1):61-8.
- ↑ Kasimir MT, Rieder E, Seebacher G, Nigisch A, Dekan B, Wolner E, Weigel G, Simon P. Decellularization does not eliminate thrombogenicity and inflammatory stimulation in tissue-engineered porcine heart valves. J Heart Valve Dis. 2006 Mar;15(2):278-86.
- ↑ El-Hamamsy I, Eryigit Z, Stevens LM, Sarang Z, George R, Clark L, Melina G, Takkenberg JJ, Yacoub MH. Long-term outcomes after autograft versus homograft aortic root replacement in adults with aortic valve disease: a randomised controlled trial. Lancet. 2010 Aug 14;376(9740):524-31.
- ↑ Cebotari S, Tudorache I, Ciubotaru A, Boethig D, Sarikouch S, Goerler A, Lichtenberg A, Cheptanaru E, Barnaciuc S, Cazacu A, Maliga O, Repin O, Maniuc L, Breymann T, Haverich A. Use of fresh decellularized allografts for pulmonary valve replacement may reduce the reoperation rate in children and young adults: early report. Circulation. 2011 Sep 13;124(11 Suppl):S115-23.
- ↑ Neumann A, Sarikouch S, Breymann T, Cebotari S, Boethig D, Horke A, Beerbaum P, Westhoff-Bleck M, Harald B, Ono M, Tudorache I, Haverich A, Beutel G. Early systemic cellular immune response in children and young adults receiving decellularized fresh allografts for pulmonary valve replacement. Tissue Eng Part A. 2014 Mar;20(5-6):1003-11.
- ↑ Tudorache I, Theodoridis K, Sarikouch S, Bara C, Meyer T, Höffler K, Hartung D, Hilfiker A, Haverich A, Cebotari S. Decellularized aortic allograft vs. pulmonary autograft for aortic valve replacement in growing sheep model: haemodynamic and morphological results after implantation for 20 months. Circulation. 2014; 130:A20027.
- ↑ Tudorache I, Horke A, Sarikouch S, Ciubotaru A, Breymann T, Boethig D, Beerbaum P, Bertram H, Westhoff-Bleck M, Meschenmoser L, Cebotari S, Haverich A. Aortic Valve Replacement with Decellularized Aortic Allografts: First Clinical Results. Circulation. 2014; 130:A19959.
- ↑ www.arise-clinicaltrial.eu; www.espoir-clinicaltrial.eu