Transplantation in the Pediatric & Adult Congenital Patient

10/10/2018

Transplantation in the Pediatric & Adult Congenital Patient: Transplantation in the Pediatric & Adult Congenital Patient: Pulmonary Artery Reconstruction & Other Advanced Techniques Pulmonary Artery Reconstruction & Other Advanced Techniques Kristine J. Guleserian MD Kristine J. Guleserian MD October 6, 2018 October 6, 2018

No Financial Disclosures

Red Sox: World Series 2004, 2007, 2013

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AmSECT Pediatric Perfusion Conference Objectives October 6, 2018 • To become familiar with the epidemiology and history of congenital heart disease (CHD). Surgical Strategies: • To recognize the growing need for care of the adult congenital Transplantation in the Pediatric & Adult heart disease (ACHD) patient. Congenital Heart Patient • To identify the unique challenges in caring for the complex Kristine J. Guleserian, M.D. pediatric and ACHD patient population. Director of Heart Failure & Transplantation Nicklaus Children’s Hospital Professor of Surgery • To understand the evaluation/management of the pediatric Herbert Wertheim College of Medicine and ACHD patient in terms of surgical intervention, catheter Miami, FL intervention, transplantation and mechanical support.

Congenital Heart Disease (CHD)

• Most common birth defect. • 1% of all newborns. • 40,000 new cases/year in Unites States. • 25% require operation < 1 year of age. • Most common cause of death in infancy from any congenital malformation.

• Adults > children w/ CHD in 2000. • > 1.5 million known to be affected in 2010.

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Congenital Heart Disease Worldwide

Impact on 15-20% CHD births/million population WHO 2011

http://cba.musc.edu/cdbc/Weinstein2004/

embryology.med.unsw.edu.au

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Common Congenital Heart Lesions Annual Adult Congenital Procedures Successful Repair Expected

Putman LM et al, Eur J Cardiothorac Surg 2009;36:96-104

Epidemiology Epidemiology

1,300,000-1,500,000 1,300,000 – Survival to 18 yrs of Age with Simple, Moderate or Complex CHD – – 1980 – 85 1,000,000 – – 1,000,000 1970 – 75 Adult – Decade CHD 700,000 – 20,000 new patients/yr Born with Patients 750,000 CHD – 5% increase/yr 1960 – 65 500,000 – – 500,000 1940 – 30 300,000 – – 325,000 Hoffman 1978 Kaiser Fyler 1980 New England 100,000 – Ferencz 1985 Baltimore-DC 0 10 20 30 40 50 60 70 80 90 100 0 – Percent Survival to 18 Years Old 1970 1980 1990 2000 2010

Warnes et al. J Am Coll Cardiol 2001;37:1170-75

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Epidemiology Today >90% Survival to Adulthood

Survival to 18 yrs of Age with Complex CHD

1980 – 80

1970 – 50 Decade Born with CHD 1960 – 15 1% D-TGA and 10% of TOF to adulthood

1940 – 5

0 10 20 30 40 50 60 70 80 90 100 Percent Survival to 18 Years Old

Warnes et al. J Am Coll Cardiol 2001;37:1170-75. Van der Velde ET et al. Eur J Epidem 2005:20:549-57. Daebritz, Ped Cardiol 2007;28:96-104

Improved Outcomes in Congenital Heart Disease Surgical History Expanding Population of Adolescent & Adults with CHD August 26, 1938

Increased Long- • First successful surgery to Increased Mid- Term Survival Term Survival correct a congenital heart

Lower Perioperative Increased Early defect (PDA ligation) Mortality Survival • Dr. Robert Gross Improved Surgical/ Earlier Complete • Dr. John Streider Bypass Techniques/ Repair Myocardial Protection – First attempt in 1937

Advances in • Boston, MA Fetal NICU/CVICU Care Diagnosis

Incidence of CHD steady 1938 1940 1942 1944 1946 1948 1950 1952 1954

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Surgical History Surgical History

October 19, 1944 November 29, 1944 • First repair of aortic • First clinical use of the coarctation Blalock-Taussig shunt for • Dr. Clarence Crafoord tetralogy of Fallot • Stockholm, Sweden • Dr. Alfred Blalock • Vivien T. Thomas -Surgical technician -Developed technique -Animal model of PHTN

1938 1940 1942 1944 1946 1948 1950 1952 1954 1938 1940 1942 1944 1946 1948 1950 1952 1954

Dr. Helen Taussig Tetralogy of Fallot Blue Baby Clinic, Johns Hopkins “Blue Baby Syndrome”

1. Anteriorly malaligned VSD 2. Overriding aorta 3. Pulmonary stenosis 4. Right ventricular hypertrophy

25% w/ PFO, RAA

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“Blue Baby” Operation 1944 Dr. Helen Taussig, Dr. Alfred Blalock, Vivien Thomas Blalock-Taussig-Thomas (BTT) Shunt

“Open Heart Surgery” Surgical History September 2, 1952 • 1st open heart procedure (ASD closure). • Hypothermia w/ inflow occlusion. – Dr. Wilfred Bigelow, Toronto • Dr. F. John Lewis & Dr. Mansur Taufic – Dr. Richard Varco – Dr. C. Walt Lillehei • 1. Transannular patch for severe pulmonary stenosis  PI University of Minnesota 2. Right ventricle-to-pulmonary artery conduit 3. Valve-sparing technique w/ commissurotomies & intraoperative balloon angioplasty 1938 1940 1942 1944 1946 1948 1950 1952 1954

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Surgical History May 6, 1953 • First successful open heart surgery using CPB – Dr. John H. Gibbon – Jefferson Medical College • 18 year-old woman w/ ASD

• First “open” ACHD operation

1938 1940 1942 1944 1946 1948 1950 1952 1954

Early Surgical Outcomes: Early Surgical Outcomes: Mortality Mortality

C. Dennis 1952 2/2 100% C. Dennis 1952 2/2 100% J. Gibbon 1953 5/6 83.3% J. Gibbon 1953 5/6 83.3% J. Helmsworth 1953 1/1 100% J. Helmsworth 1953 1/1 100% D. Dodrill 1953 2/2 100% D. Dodrill 1953 2/2 100% G. Clowes 1953 2/2 100% G. Clowes 1953 2/2 100% W. H. Mustard 1953-54 5/5 100% W. H. Mustard 1953-54 5/5 100%

Total 17/18 94.5% Total 17/18 94.5%

Moratorium on Cardiopulmonary Bypass

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Dr. C. Walton Lillehei Cross Circulation Cross Circulation

1954 • First successful repairs – VSD – Tetralogy of Fallot

• University of Minnesota

1938 1940 1942 1944 1946 1948 1950 1952 1954

Cross Circulation VSD Repair: March 26, 1954

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Mayo-Gibbon Heart Lung Bypass Machine Surgical History

March 22, 1955 • Dr. John Kirklin • Mayo Clinic • VSD closure with Gibbon mechanical pump- oxygenator • By May, 4/8 patients survived to discharge

• 94.5%  50% mortality!!!

1938 1940 1942 1944 1946 1948 1950 1952 1954

Tetralogy of Fallot s/p Blalock-Taussig shunt 1972 s/p Tetralogy of Fallot repair 1976

“Blue Baby” Syndrome

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Pulmonary valve implantation May 8, 2015

Shaun White Olympic Snowboarder

“The Flying Tomato”

Surgical Pulmonary Valve Replacement Transcatheter Pulmonary Valve Replacement

Carpentier-Edwards PERIMOUNT Magna Ease Bovine Pericardial Bioprosthesis Melody™ Sapien™ • Bovine jugular venous • Bovine pericardial valve segment tissue leaflets • Platinum-Iridium Stent

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What About the Failures?

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Pediatric Heart Transplantation

Stephanie Fae Beauclair “Baby Fae”

HLHS s/p transplant @ 12 days of age Died 19 days later Baboon to Human Heart Transplant Loma Linda, CA October 26, 1984

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2 days of age, 2.2 kg s/p TOF repair w/ septal hematoma On ECMO support Referred for transplant

2 y/o w/ HLHS w/ rASD s/p Norwood s/p bidirectional Glenn FailingHLHS Glenn physiology s/p Norwood Highlys/p sensitized Bidirectional Glenn

Mode-severe TR Severe RV dysfunction

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July 21, 2011 Berlin Heart EXCOR® Ventricular Assist Device (VAD) FDA Approved December 2011

LVAD, BIVAD, Systemic VAD (single ventricle)

Berlin Heart Systemic VAD Removal, Orthotopic Heart Transplantation w/ LPA Stent Removal, Bilateral Branch PA Reconstruction & Aortic Arch Reconstruction Parental Perspective ?

October 6, 2011

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Hypoplastic Left Heart Syndrome (HLHS) s/p Norwood/BT Shunt s/p Bidirectional Glenn shunt s/p Fenestrated Fontan

Failing Fontan physiology

Hypoplastic Left Heart Syndrome (HLHS) Unknown Diagnosis

• Premature, 10 day-old • Birth weight < 2.5 kg • Mechanical ventilation • Cardiac arrest  CPR • Lactate 17, pH 6.5 • Creatinine 2.6, INR 2.6 • PGE1, vasopressin, epinephrine • ECHO  HLHS, poor RV function

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Resuscitative Bilateral PA Banding Strategy

Prostaglandin  maintenance of ductal patency

Balloon atrial septostomy  IAS/RAS

Plans for convention Stage 1 Norwood Procedure PGE1  Ductal Stent if no recovery

Ductal stent only if not a candidate for Norwood (not if vascular ring present or -Persistent poor RV function diminutive ascending aorta) -Significant AVVR -Persistent end-organ dysfunction -Intracranial hemorrhage

Adapted, Galantowicz

J Thorac Cardiovasc Surg 2013;145:206-14

Guleserian et al, J Thorac Cardiovasc Surg 2013

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s/p Norwood/3.5mm RMBTS

Post-Operative Course s/p Balloon Atrial Septostomy & Resuscitative Bilateral PA Banding

• Extubated • Off epinephrine, vasopressin • Normalization of INR, Creatinine • Tolerating oral feeds

• Elective Norwood Procedure & PA debanding

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Ductal Stenting, Reassessment of PA Bands

What if Persistent Poor Ventricular Function? Severe TR? Both?

HLHS or variant HLHS s/p Hybrid Procedure

End-to end descending thoracic aortic anastomosis & Brachiocephalic vessel “island” to donor arch HLHS/variant HLHS Bilateral PA bands Ductal stent Biatrial anastomoses

PA reconstruction w/ donor PA (hilum-to-hilum) PA debanding or donor pericardial patch +/- PA reconstruction Ductal stent removal Aortic arch reconstruction

VA Sebastian et al . J Card Surg 2010

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Types of ACHD Patients

1. Undiagnosed or misdiagnosed CHD (w/ PHTN).

2. Previously repaired and “cured” patient (TOF, D-TGA, What About the ACHD Patient? CC-TGA, truncus arteriosus, coarctation, complete AV canal).

1. Previously palliated patient (shunted single ventricle  completion of Fontan circulation).

2. Heart failure patients (considered for transplantation).

The Unoperated Patient w/ CHD The Unoperated Cyanotic Patient

• Septal defects (ASD, VSD, AV Canal) • Many reach adulthood w/ cyanotic CHD (TOF). • Tetralogy of Fallot • Presence of aortopulmonary collaterals. • Intraoperative nightmare. • Sinus venosus defect +/- PAPVC • If well saturated  coil embolization. • Coarctation of aorta • Corrected transposition (CC-TGA) • Excessive pulmonary venous return. • Anomalous coronary artery (AAOCA) – Obscuration of operative field • Aortic stenosis (bicuspid aortic valve) – Impaired myocardial protection – Left-sided volume overload • Scimitar syndrome – Systemic underperfusion (cerebral, renal, mesenteric)

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Adults With CHD: Challenges CHD = A Chronic Disease

• Told they were “cured”.

• Do not receive appropriate surveillance or lost to follow up. Arrhythmias

• Community care---or no care at all. Vascular Valve disease disease • Not educated about their heart disease & what to expect. ACHD • Residual lesions or sequelae of disease/operation. Endocarditis Ventricular dysfunction • Development of co-morbidities. Pulmonary hypertension • No records

Cardiac Transplantation in Patients with Congenital Heart Disease (CHD) • Cardiac transplantation for CHD incorporates aspects of reparative & replacement surgery.

• Intracardiac congenital malformations are replaced.

The prevalence of heart transplantation among adult • Extracardiac malformations (congenital, acquired, or iatrogenic)  considerable challenges. recipients decreased by 28% over time (P<.001) and – Anatomic variants. increased among patients with adult congenital heart – Conduits, residual shunts, stents, etc. disease by 41% (P<.001). – Adhesions, pseudoaneurysm, thrombus burden, etc. • Comprehensive operative plan = essential.

J Thorac Cardiovasc Surg 2010

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Cardiac Transplantation in Patients with Congenital Heart Disease (CHD) Cardiac Transplant: Bi-atrial Anastomosis

• Donor team – Harvest appropriate donor tissue to allow for adequate reconstruction. – Timing must be coordinated.

• Recipient team (surgical-anesthesia-perfusion) – Reoperative median sternotomy – Vascular access  safe establishment of cardiopulmonary bypass and full cardiac support. – AP collaterals  adequate cooling/venting. – Blood products  anticipated bleeding/coagulopathy.

Cardiac Transplant: Bi-caval Anastomosis

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Residual Shunts Tetralogy of Fallot w/ Pulmonary Atresia & Hypoplastic Pulmonary Arteries

Atretic Pulmonary Valve Baffle leak s/p Atrial Switch Baffle leak s/p Fontan

Baffle Obstruction s/p Atrial Switch for Branch Pulmonary Artery Stenosis and D-TGA Pulmonary Insufficiency s/p TOF Repair

48 year-old s/p TOF repair 26 year-old s/p TOF repair

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RVOT Pseudoaneurysm s/p TOF Repair Ventricular Dysfunction & Dilation

TOF s/p Repair With RV DORV s/p Repair With Diastolic Dysfunction Diastolic Dysfunction

Atriopulmonary Fontan Endocarditis

Thrombus formation Thrombus formation, atrial dysrhythmias (atrial flutter)

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Reoperative Right Femoral Cutdown 8mm Dacron chimney graft

Donor Heart -Innominate vein Bilateral Superior Vena Cavae (B SVC) -Aortic arch -Branch PAs -Pulmonary veins -Pericardium

JM Chen. Op Tech Thorac Cardiovasc Surg 2014

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Bilateral Superior Vena Cavae (B SVC): Bilateral Superior Vena Cavae (B SVC): L SVC  roof of LA L SVC  roof of LA

JM Chen. Op Tech Thorac Cardiovasc Surg 2014 JM Chen. Op Tech Thorac Cardiovasc Surg 2014

B SVC: L SVC  Roof of LA B SVC: L SVC  Roof of LA Intra-atrial baffle along roof of LA Intra-atrial baffle along floor of LA

JM Chen. Op Tech Thorac Cardiovasc Surg 2014 JM Chen. Op Tech Thorac Cardiovasc Surg 2014

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 B SVC: L SVC Coronary Sinus Biatrial Anastomosis “Roofed” pathway “Roofed” pathway

JM Chen. Op Tech Thorac Cardiovasc Surg 2014 JM Chen. Op Tech Thorac Cardiovasc Surg 2014

Bicaval Anastomosis Bilateral Superior Vena Cavae: “Roofed” pathway Modification of Recipient Cardiectomy

JM Chen. Op Tech Thorac Cardiovasc Surg 2014 Mora B, Huddleston C. Curr Cardiol Rev 2011

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Heterotaxy Syndrome Transposition of the Great Arteries Management of Ipsilateral Hepatic Veins, L IVC (TGA) D-TGA s/p Mustard D-TGA s/p Senning L-TGA

Extra Donor & Recipient Aorta Extra donor PA

Pericardial baffle of hepatics (or L IVC) to RA

del Nido PJ et al, Surg Tech Ped Heart Transplant, ISHLT Monograph 2007 JM Chen. Op Tech Thorac Cardiovasc Surg 2014

Transposition of the Great Arteries Pulmonary Artery Distortion Sutured arteriotomy (TGA) D-TGA s/p Mustard D-TGA s/p Senning L-TGA

Leftward translocation of PA anastomosis

JM Chen. Op Tech Thorac Cardiovasc Surg 2014 JM Chen. Op Tech Thorac Cardiovasc Surg 2014

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Pulmonary Arterioplasty Discontinuous Pulmonary Arteries Donor MPA/branch PA spatulation

Posterior view

JM Chen. Op Tech Thorac Cardiovasc Surg 2014 del Nido PJ et al, Surg Tech Ped Heart Transplant, ISHLT Monograph 2007

HLHS/variant HLHS s/p Hybrid Procedure Transplant w/ Arch Reconstruction s/p Hybrid Procedure (+/- Branch PA plasty)

JM Chen. Op Tech Thorac Cardiovasc Surg 2014

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Situs Inversus Donor Heart: LA Cuff Modification

Vricella et al, J Thorac Cardiovasc Surg 1998

Vricella et al, J Thorac Cardiovasc Surg 1998 Vricella et al, J Thorac Cardiovasc Surg 1998

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Vricella et al, J Thorac Cardiovasc Surg 1998 Vricella et al, J Thorac Cardiovasc Surg 1998

Situs Inversus: Donor Cardiectomy Modification Situs Inversus:

B BDG takedown

Left-sided PVs oversewn PA spatulation

Long L IVC-RA cuff

Deuse T, Reitz B. J Thorac Cardiovasc Surg 2010 Deuse T, Reitz B. J Thorac Cardiovasc Surg 2010

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Situs Inversus: Situs Inversus Implant Technique L SVC-L IV anastomosis

Posterior PA anastomosis

Recipient aortic stump oversewn

End-to-side aortic anastomosis

Apex rotated

L IVC anastomosis

Deuse T, Reitz B. J Thorac Cardiovasc Surg 2010 Deuse T, Reitz B. J Thorac Cardiovasc Surg 2010

Situs Inversus: Transplant Technique

Separate atriotomy anterior to L PVS = neo LA

Closure of leftward aspect RA cuff

Mobilization of recipient atrial Transplantation in adults with CHD is associated with a relatively high operative mortality septum & anastomosis to LA secondary to increased bleeding, infection, and graft failure compared with non-congenital free wall heart disease transplant recipients

Biatrial anastomosis

Mora B, Huddleston C. Curr Cardiol Rev 2011

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Adult Heart Transplants Kaplan-Meier Survival by Diagnosis (Transplants: January 1982 – June 2015)

100 CHD (N=2,363) ICM (N=45,038) NICM (N=49,457)

Retransplant (N=3,051) VCM (N=3,926)

75 Median survival (years): CHD=15.0; ICM=9.6; NICM=11.9; Retransplant=6.4; VCM=11.0 Operative Preparation is Key!!!

50 Survival (%) Survival

All pair-wise comparisons were significant at p < 0.05 except CHD vs. NICM. 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 Years For some retransplants diagnosis other than retransplant was 2017 reported, so the total number of retransplants may be greater. JHLT. 2017 Oct; 36(10): 1037-1079

Best to Avoid…. Utility of 3D Models

• Understand the anatomy

• Communicate the anatomy – Patients & families – Providers – Students

• Plan intervention – Cardiac catheterization – Cardiac surgery “NURSE!!!!! GET ON THE INTERNET, GO TO CONGENITALHEARTSURGERY.COM, SCROLL • Practice/simulate intervention DOWN AND CLICK ON THE ‘ARE YOU TOTALLY – Cardiac catheterization LOST ? ’ ICON” – Cardiac surgery Bartel, Eur Heart Journal 2017

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D-Transposition of Great Arteries (D-TGA) w/ VSD 3D Printing Program: Library of Heart Models

SketchFab Platform: Storage & Sharing

Interactive Holographic Technology

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OPTN: Organ Procurement & Transplantation Network Donors/Recipients

https://optn.transplant.hrsa.gov

HeartWare HVAD/MVAD

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HeartMate III Jarvik Heart

Failing Fontan Ebstein’s Anomaly Failing Fontan

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SynCardia Total Artificial Heart (TAH)