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Xenotransplantation? LA CHIRURGIA DELLE CARDIOPATIE CONGENITE: EVOLUZIONE E COMPLESSITA' Gaetano D. Gargiulo P e d i a t r i c C a r d i a c S u r g e r y and GUCH Unit The Heart Birth prevalence: 1.35 million babies/years Birth prevalence 1% of live births Birth prevalence over time and GUCH Unit S u r g e r y C a r d i a c Birth prevalence of CHD P e d i a t r i c worldwide Open issues… CV centers Cardiac surgeons Potential money Congenital heart disease is the most common class of major malformations in humans and major source of morbility and paediatric mortality around the world. P e d i a t r i c C a r d i a c S u r g e r y and GUCH Unit Where are Where we CHD now? Have CHDs always been with us ? and GUCH Unit DETMOLD S u r g e r y CHILD C a r d i a c 6.500 years ago P e d i a t r i c Hypoplastic Left Heart Syndrome P e d i a t r i c C a r d i a c S u r g e r y and GUCH Unit THE HISTORY THE 1936 MAUDE ABBOTT (1869 – 1940) P e d i a t r i c C a r d i a c S u r g e r y and GUCH Unit …A HUNDRED YEARS AGO… The first surgical repair of CHD : Ductus ligation Robert Gross, MD Lorraine Sweeney (1905-1988) 7-year-old 25 YEARS LATER …treatment of "Blue Babies" …the beginning of surgical era Helen B. Taussig (1898–1986) Alfred Blalock (1899 –1964) Eileen Saxon,15 m …treatment of "Blue Babies" …the beginning of surgical era Blalock-Taussig shunt JAMA 1945;128:189 –202. The American Weekly, February 17, 1946 N.Y. Herald Tribune, Febr. 15,1946 The dark side of the moon Vivien Thomas (1910 – 1985) The first intracardiac repair Altre soluzioni ASD repair Cross circulation The Evolution of Technology – How It's Changed Our Lives Altre soluzioni “I have come to the field late, that the history of congenital heart surgery was over.” 1957 - John Kirklin,Mayo Clinic 2000 -Pediatric Cardiac surgery – S.Orsola-BO A. Castaneda - Boston Resident at University of Minnesota The Evolution of Surgery and GUCH Unit CHD S u r g e r y European Journal of Cardio-Thoracic Surgery, 25:6;911–924 Where are C a r d i a c we now? P e d i a t r i c 1377 1400 1005 1200 948 1000 800 600 400 200 LBW <2,5 Kg 11,4% 0 WLBW <1,5Kg 6,4% SI MPLE CHD MID COMPEXITY Preterm <600gr 250pts CHD COMPLEX CHD BOLOGNA EXPERIENCE: FROM 2010 TO TODAY ADVANCES IN TREATMENT OF CHD Anatomic definition Accurate fetal and postnatal diagnosis Tailored surgical procedure Optimal post-operative intensive care Improved biocompatibility of CPB material Neonatal surgery Transposition of great arteries: arterial switch 1975 1981 2014 33 pts 614 pts/year First operation Mortality Mortality 52% 2% High risk procedure HLHS and GUCH Unit Norwood procedure S u r g e r y Natural history C a r d i a c P e d i a t r i c HYBRID PALLIATION and GUCH Unit ▪ Bridge to Norwood S u r g e r y ▪ Bridge to BCPA C a r d i a c P e d i a t r i c Circ Res. 2017;120:923-940 Advances in Genetics of CHD: From an Acorn to a Oak Summary of Genes Implicated in Tetralogy of Fallot and Their Clinical Relevance Cardiology in Review 2018;26: 86–92 Hamburger and Hamilton chick embryos and GUCH Unit S u r g e r y SHF cells in the mid-portion SHF cells into outflow tract of the caudal wall of the outflow tract C a r d i a c P e d i a t r i c SHF cells are located at base of the outflow on the left side Looping Advances in Embryology of CHD Heart development - timeline ALMA MATER STUDIORUM – UNIVERSITA’ DI BOLOGNA LEZIONI DI CARDIOCHIRURGIA – Prof. G.D.Gargiulo Archives of Cardiovascular Disease (2009) 102, 59—63 ALMA MATER STUDIORUM – UNIVERSITA’ DI BOLOGNA LEZIONI DI CARDIOCHIRURGIA – Prof. G.D.Gargiulo Advances in Prenatal Diagnosi of CHD 20 W GA ECHO 20 W GA Doppler 32 W GA MRI Screening procedure for LV dimension and GUCH Unit S u r g e r y Up to 300 prenatal screening C a r d i a c for CHD at S. Orsola University P e d i a t r i c Hospital Birth Defects Research. 2019;111:389–394 FETAL HEART REPAIR Birth Defects Research. 2019;111:389–394 FETAL HEART REPAIR ACCURATE ANATOMIC DEFINITION NEW IMAGING CTV 4D MRI and GUCH Unit ▪Better understand anatomy S u r g e r y ▪Visualization of patho-physiology C a r d i a c ▪Planning of operation ▪Simulating on patient characteristics P e d i a t r i c PROPORTION OF ALL DEATHS GUCH POPULATION The Heart Transplantation Alexis Carrel (1873 – 1944) Il miracolo dei SS. Cosma e Damiano - Alonzo de Sedano, 1500 c.a. Welcome Istitute, Londra Nobel prize, 1912 Profeta Ezechiele – Vecchio testamento VI sec. AC. “Io ti darò un nuovo cuore ed un nuovo spirito, toglierò dalla tua carne il cuore di pietra e ti metterò un cuore di carne” The first Human Heart Transplant 3 December 1967 Christiaan Barnard (8 November 1922 – 2 September 2001) Louis Washkansky Mr Darvall Denise Darvall The dark side of the moon Hamilton Naki New York Times “We are trying to make one whole new individual out of two individuals who did not have a chance for survival” A. Kantrowitz, Maimonides Medical Center, Brooklyn and GUCH FirstUnit pediatric heart transplant ... S u r g e r y three days later, 6 December 1967. C a r d i a c P e d i a t r i c 19-days-old boy with Neonatal Ebstein Heart transplant ... a long journey. 3 December D. Cooley Barnard Pediatric Htx – First Heart transplant first long-term successful survivor SynCardia TA H First Canine Re jection recognized successfully used as autotransplant and has central problem bridge-to-transplant allotransplant for Transplanted 26 Ott. 1984 performed by Lo wer Hearts Le onard Ba iley and Sh umway Xenotransp lantation 1950 1960 1967 1970 1980 1990 2000 2010 2015 1964 - Ha rdy Cyclosporine start to be used in Xenotransplant solid organ transplant for avoid Experimental Chimpanzee- rejection Pediatric First Child to go back orthotopic Human ventricular assist to school with LVAD Canine Heart devices Transplant performed by 6 December - Ka ntrowitz Webb and Goldberg First Neonatal transplant Leonard Bailey – Loma Linda University 26 Ott. 1984 800 Età / Anni 700 <1 1-5 6-10 11-17 600 s t n a l 500 p Heart s n a r T 400 f o r e b 300 m transplantationu N 200 160.000 140.000 100 120.000 0 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06 07 08 09 10 11 12 13 14 15 16 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 9 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 100.000 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 140.000 80.000 60.000 from 1982 to 2016. 40.000 20.000 - 125.000 All Adult 15.000 Pediatric and GUCH Unit Results of pediatric S u r g e r y heart transplantation C a r d i a c P e d i a t r i c • Xenotransplantation? and GUCH Unit And… when will the S u r g ehuman r y organs end? C a r d i a c • VAD or TAH? P e d i a t r i c and GUCH Unit Lamassù Assiro S u r g e rXenotransplantation y ? C a r d i a c 2018 P e d i a t r i c MECHANICAL CIRCULATORY SUPPORT: A NEW OPTION and GUCH Unit VAD: Bridge to Transplant Bridge to S u r g e r y Decision/Recovery Bridge to Destination TAH: C a r d i a c Bridge to Transplant Bridge to Decision Bridge to Destination P e d i a t r i c VAD – Ventricular Assist Device and GUCH Unit S u r g e r y VAD C a r d i a c P e d i a t r i c VAD and GUCH Unit 50% reduction in Pediatric S u r g e r y Heart transplant waiting2009-2017 list mortality in the new era 2009-2016 C a r d i a c P e d i a t r i c J Heart Lung Transplant 2015;34:82-8. JHLT. 2018 Oct; 37(10): 1155-1206 Berlin Heart & Heart transplant and GUCH Unit S u r g e r y C a r d i a c HeartWare VAD P e d i a t r i c Berlin Heart and GUCH Unit S u r g e r y Our experience C a r d i a c HeartWare P e d i a t r i c P e d i a t r i c C a r d i a c S u r g e r y and GUCH Unit Total heart artificial “The best way to predict the future is to create it” Abraham Lincoln NEW THERAPIES Current Use: New Available Technologies: Future: As part of a repair (ASD, Vehicle for Enhance Resident VSD, Valve repair, etc.) tissue Repair Structural replacement of Material Used: Material Used: Pericardium, PTFE Tissue Engineered Pericardium, Cardiac Tissue Decellularized Extracellular matrix NEW THERAPIES The future : Tissue Engineering for CHD correction Optimal characteristics ▪ absence of immunogenicity ▪ growth potential proportional to somatic enlargement ▪ excellent durable hemodynamic profile ▪ availability indifferent sizes ▪ pliability ▪ association with minimal thromboembolism risk ▪ not requiring anticoagulation ▪ low incidence of structural degeneration ▪ resistance to calcification NEW THERAPIES Circulation.
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