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

Birth prevalence: 1.35 million babies/years

Birth prevalence

1% of live births 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 Birth prevalenceBirth Birth prevalenceBirth worldwide over time time over of CHD 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 we CHD now? Have CHDs always been with us ? 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 DETMOLD 6.500 CHILD years ago 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 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… YEARS HUNDRED …A 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

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 we CHD now? European Journal of Cardio - Thoracic Surgery, 25:6;911 – 924 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% 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 Norwood High Natural Natural risk HLHS procedure procedure history 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 PALLIATION ▪ ▪ Bridge Bridge Bridge HYBRID to to BCPA Norwood 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 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 SHF cells cells into outflow tract Hamburger and Hamilton and Hamilton Hamburger chick of theoutflowon the side left at are located base SHF cells outflow tract of thecaudal wall of the SHF embryos cells cells in themid - portion 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 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 prenatal screening screening prenatal S. Screening procedure Screening Orsola for LV dimension LV for Upto Hospital for CHD for CHD at University University 300 Birth Defects Research. 2019;111:389–394

FETAL HEART REPAIR Birth Defects Research. 2019;111:389–394

FETAL HEART REPAIR ACCURATE ANATOMIC DEFINITION 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 ▪ ▪ ▪ ▪ characteristics Planning of operationPlanning of Visualization anatomy understandBetter Simulating on patient Simulating NEW IMAGING NEW CTV 4D MRI 4D CTV patho - physiology PROPORTION OF ALL DEATHS GUCH POPULATION The

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 (8 November 1922 – 2 September 2001) Louis Washkansky Mr Darvall Denise Darvall

The dark side of the moon 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 First pediatric heart 6 December 1967. three days later, transplant ... 19 - days - old boyNeonatal with A. havea chancefor survival two individualswho didnot wholeout individualof new “ New York Times Kantrowitz We aretrying to makeone , Maimonides Ebstein Medical Center, Brooklyn ” 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 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 Heart transplantation from 1982 to 2016.

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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. 2017;136:2373–2385. 3D PRINTING 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     Teachingpurposes simulation PatientPre for specific model specificmodel for PathologyFunctional specific anatomy patient of Model CARDIAC CARDIAC PRINTING PRINTING 3D 3D - surgery 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 DECELLULARIZATION 3D PRINTING PRINTING 3D CARDIAC CARDIAC ORGAN ORGAN First First 3d - printed printed Heart made from made from human cell on April 2019 VIRTUAL REALITY IN CARDIAC SURGERY

Virtual Heart at Lucile-Packard Children’s Hospital 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 CongenitalDisease Heart Interventional Proceduresfor Executing and Planning in Roleof Computational Modelling FLUID DYNAMICS FLUID COMPUTATIONAL Atlanta,Georgia Children Emory University School of Medicine, Can J Can Cardiol ’ s Healthcare s of Atlanta, . 2017 2017 Sep;33(9):1159 - 1170. SCIENCE AND CHARITY

Scienza e Carità – P. Picasso - 1897 “Gentlemen, we will chase perfection, and we will chase it relentlessly, knowing all the while we can never attain it. Bu t along the way, we sh all catch exc ellenc e.” Vince Lombardi

GRAZIE…