2. Scope of the talk…
Cardiac transplant down the years
Indications n Contraindications
Pre-transplant evaluation
Donor heart selection procedure
The procedure itself: How do we go about
Post operative management
Our scenario: India n Star Hospital
3. James Hardy
1st heart transplant/ Xenotransplant
University of Mississippi, USA
Chimpanzee—> Boyd Rush
24/01/1964
Heart beated for 1 hour, No consciousness—> Expired
4. Christian N Bernard
1st Human Heart Transplant
Groote Schuur Hospital, Cape Town
03/12/1967
54 yrs: Louis Washkansky
Died after 18 days, pneumonia
4
5. Baby Fae
1st neonatal heart transplant
Leonard L Bailey
1984, Loma Linda, California
HLHS: Baboon heart: 21 days (Life-32 days)
6. Baby Moses
1st successful infant cardiac transplantation-HLHS
Leonard Bailey
Loma Linda, California
20th Nov, 1985
Alive
7. P Venugopal
India’s first heart transplant
3rd August, 1994
Recipient: Devi Ram: 40 years old heavy industry worker:
Cardiomyopathy
Donor: 35 years old lady, brain haemorrhage
8. India’s 1st pediatric heart transplant
Gleb Kudriavtceva
Russian; Restrictive cardiomyopathy
Fortis, Chennai
19 Dec, 2014
Dr. K R Balakrishnan+ Dr Suresh Rao
10. The numbers speaks…
International society for heart+ Lung transplantation (ISHLT)
Only 10% of overall heart transplants
9566 pediatric transplants: 1982-2009
350-450/ year
Primary indications: CHD, Cardiomyopathy
6% Retransplants (> 5 years after 1st-50%)
14. Heart transplant for
Cardiomyopathy-DCM
>50% of all heart failures in kids
5 year survival: 40-83%
Acute fulminant myocarditis requiring mechanical support: Good prognostic indicator—>
Upto 50-80% will have complete resolution of DCM within 2 years+ avoid transplantation
15. Heart transplant for
Cardiomyopathy-HCM
2nd MC CM: 25-42%
Only 5%: Peds heart transplants
Malformation syndromes (Noonan’s+ Beckwith- Wiedemann syndrome): 25% of HCM cases
Risk factors for death or transplantation: < 1 year presentation, Echo findings of lower initial
shortening fraction+ higher initial LV posterior wall thickness
DMD+ other muscular dystrophies—> CM+ Heart failure
16. Heart transplant for
Cardiomyopathy-RCM
LV with normal size+ wall thickness—> Poor compliance+ Restrictive filling
2.5-3% CMs in kids: But 12% of heart transplants in CM patients
Long term survival: < 50% at 2 years
Incidence of progressive pulmonary HT increased
17. Heart transplantation for CHD
1. Primary therapy:
HLHS, PA with IVS, RV dependent coronary circulation, SV lesions with anomalous
pulmonary venous return+ severe valvular disease
2. Therapy in previously palliated / repaired defects: 40% of all Peds heart transplants
Successful palliative procedure: Patients survival increased to adulthood
Morbidities: CHF, valvular diseases, PHT, arrhythmias
18. Was the 1st one not enough???
Recipients have 2-3%: Annual risk of death/ graft failure: Causes-> Graft coronary vasculopathy, acute or chronic rejection
Indications for retransplantation:
Graft coronary vasculopathy: 51%
Non-specific graft failure: 16%
Acute rejection: 9%
Chronic rejection: 7%
Primary failure: 5%
Hyperacute rejection: 3%
Others: 10%
19. Retransplantation
6% of pediatric heart transplants
Survival after reimplantation< Primary transplantation if done within 5 years
Intertransplant interval> 5years: Survival comparable to primary
22. CM+ CHD in Pediatric patients
CLASS-1 Indications
Indicated as therapy for stage D heart failure associated with systemic ventricular
dysfunction in patients with CM/ previous repaired/ palliated CHD (LOE- B)
As therapy for stage C heart failure in pediatric heart disease associated with severe
limitation of exercise and activity. If measurable, such patients would have a peak
maximum oxygen consumption 50% predicted for age and sex (LOE- C)
As therapy for stage C heart failure associated with systemic ventricular dysfunction in
pediatric patients with CM/ previously repaired/ palliated CHD when heart failure is
associated with significant growth failure attributable to heart disease (LOE-B)
23. CM+ CHD in Pediatric patients
CLASS-1 Indications
As therapy for stage C heart failure in pediatric heart disease with associated near sudden
death and/or life-threatening arrhythmias untreatable with medications or an implantable
defibrillator (LOE- C)
As therapy for stage C heart failure in pediatric RCM disease associated with reactive
pulmonary hypertension (LOE- C)
In presence of other indications for heart transplantation, heart transplantation is feasible in
patients with pediatric heart disease and an elevated pulmonary vascular resistance index 6
Woods units/m2 and/or a transpulmonary pressure gradient 15 mm Hg if administration of
inotropic support or pulmonary vasodilators can decrease pulmonary vascular resistance to
6 Woods units/m2 or the transpulmonary gradient to 15 mm Hg (LOE-B)
24. CM+ CHD in Pediatric patients
CLASS-2A Indications
As therapy for stage C heart failure in pediatric heart disease associated with reactive
pulmonary hypertension and a potential risk of developing fixed, irreversible elevation of
pulmonary vascular resistance that could preclude orthotopic heart transplantation
in future (LOE- C)
25. CM+ CHD in Pediatric patients
CLASS-2A Indications
Certain anatomic and physiological conditions likely to worsen natural history of CHD in
infant patients with a functional single ventricle, which can lead to use of heart transplantation
as primary therapy
Conditions include:
(1) Severe stenosis or atresia in proximal coronary arteries
(2) Moderate to severe stenosis and/or insufficiency of the atrioventricular and/or systemic
semilunar valve(s)
(3) Severe ventricular dysfunction (LOE- C)
26. CM+ CHD in Pediatric patients
CLASS-2A Indications
Several anatomic and physiological conditions likely to worsen natural history of previously
repaired or palliated CHD in pediatric patients with stage C heart failure that may lead to
consideration for heart transplantation without severe systemic ventricular dysfunction,
including:
(1) Pulmonary hypertension and a potential risk of developing fixed, irreversible elevation of
PVR that could preclude orthotopic heart transplantation in future
(2) Severe aortic or systemic A-V valve insufficiency that is not considered amenable to surgical
correction
(3) Severe cyanosis that is not considered amenable to surgical correction
(4) Persistent protein-losing enteropathy despite optimal medical-surgical therapy (LOE-C)
27. CM+ CHD in Pediatric patients
CLASS-2B Indications
Efficacy of heart transplantation as therapy for pediatric heart disease is not established for:
Patients with previous infection with hepatitis B/ C/ HIV infection (LOE- B)
Patients with a history of recent use of illicit drugs/ tobacco/ alcohol abuse (LOE- B)
Patients with a history of psychological, behavioral, or cognitive disorders; poor family
support structures; or documented noncompliance with previous therapies that could interfere
with successful performance of care regimens after transplantation (LOE- B)
28. CM+ CHD in Pediatric patients
CLASS-3 Indications
Not efficacious when:
Heart disease is associated with severe, irreversible disease in other organ systems
or when it is part of a severe, irreversible, multisystemic disease process. Multiorgan
transplantation may be considered (LOE- C)
When heart disease is associated with severe, irreversible, fixed elevation of PVR
(LOE- C)
●Not feasible in presence of severe hypoplasia of central BPAs or pulmonary veins (LOE- C)
●Limited supply of pediatric donors, especially infant donors, makes heart transplantation not a
feasible standard therapy for any specific congenital heart lesion (LOE- B)
29. Cardiac Retransplantation in
pediatric patients
Class I
● Indicated in children with abnormal ventricular function and at least moderate graft
vasculopathy (LOE- B)
Class IIA
● Indicated in children with normal ventricular function and at least moderate graft vasculopathy
(LOE- B)
Class III
● Should not be performed during an episode of ongoing acute allograft rejection, even in
presence of graft vasculopathy (LOE- B)
● Not efficacious when performed during first 6 months after primary transplantation (LOE- B)
31. Assessment of…
Cardiovascular anatomy+ haemodynamics
Presence of chronic non- cardiac disease+ magnitude of dysfunction in other organ systems
Magnitude of sensitisation to HLA+ HLA specific antibodies
Psychosocial evaluation of patient+ family: Screen for psychological/ cognitive/ behavioral/
adjustment disorders
33. Criteria for initiating evaluation in
utero with fatal listing…
CHD not considered correctable by postnatal surgical repair
Normal pulmonary artery anatomy
Estimated fatal weight > 2kg
>35 weeks gestation
Normal chromosomes
No significant extra cardiac defects identified by prenatal level 3 USG
33
34. Contraindications: Absolute
Irreversible PAH (PVRI> 6 WU/m2)
Inactive systemic infection
Uncontrolled malignancy
Severe primary renal/ hepatic failure
Major abnormalities of CNS
Severe dysmorphism
36. Donor Hearts selection
Must meet requirements for brain death
Consent from nearest relative
ABO compatibility favoured (Avoids hyper acute rejections)
Donor should be 1-3x recipient weight
ECHO: Shows normal cardiac anatomy+ function post resuscitation
Mechanism of death important: Possible myocardial damage/ contusion
If cardiac arrest and CPR given—> Duration of arrest important
37. Donor Hearts selection
Should have no active infections (HIV/ Hep B)/ Malignancy
Donor evaluation: Physical exam, assessment of haemodynamics, ionotropes during
resuscitation, renal function, CXR, ECG
Length of ischemic time+ Travel distance
Visual inspection by procurement tean—> Necessary before final acceptance of heart
39. Kids have issues quiet different
from adults…
Kids of CHD often have undergone some surgery for palliative procedures
Kids with CHD—> Complex anatomy—> Needs tailoring of implantation techniques
Highly sensitised from previous BTs+ homograft materials for repairs
Elevated panel reactive antibodies—> Higher chances for rejection complications
PVR often high—> Post op management difficult
40. Heart Procurement Technique
Team work: Not a single man’s game
Transplant procurement team ( Also needed lung and/ or abdominal team)
Median sternotomy taken
Begin dissection by separating MPA+ Aorta—> Allows easy placement of cross clamp
SVC+ Innominate veins dissected free; Azygous ligated+ divided; Attachments surrounding
SVC+ IVC freed sharply
Full systemic heparinisation dose: 300iu/ kg
Aortic cross clamping+ cardioplegia solution administered
40
41. Heart Procurement Technique
cont…
Pressure monitoring of aortic root needed—> To avoid high perfusion pressure in pediatric
[patients+ injury to coronary microvasculature
PV incised to decompress left heart; IVC incised to decompress rt. heart
Ice saline slush poured on heart
CARDIECTOMY: Begins by dividing IVC
LA incised circumferentially to preserve left atrial cuff for lungs (Veins can be divided at pericardial
reflection if lung not procured)
MPA divided at bifurcation if lungs procured; if not BPAs can be divided at pericardial reflection
42. Heart Procurement Technique
cont…
Ascending aorta divided at level of innominate artery (If for HLHS: Aorta harvested to level
of proximal descending segment)
Heart placed in cold saline 4 dec C in handheld cooler for transport
CONSIDERATION OF RECIPIENT ANATOMY IS ESSENTIAL IN PATIENTS WITH
CHD—> MAY ALTER HARVEST TECHNIQUE TO ALLOW ADDITIONAL TISSUE FOR
ANATOMIC RECONSTRUCTION AT TIME OF IMPLANTATION
43. Post Operative Management
Before coming off CPB: Infusions initiated with dobutamine+ milrinone
Continue milrinone for several days: Changes in PVR unpredictable+ sudden
iNO: For known elevated rt sided pressure kids: Start while on CBP, Continue several days
Pacing: To increase HR, To reduce diastolic filling time
After chronotropic+ inotropic infusions weaned—> Patients require after load reduction—>
ACE-s, CCBs —> To be continued after discharge
45. Immunosuppression
Effective immunosuppression—> Paramount to successful heart transplant
Lack of consistency with frequency of induction treatment+ specific agents used
2011 ISHLT Guidelines: Combination of calcineurin inhibitor+ cell cycle inhibitor +
steroid
ISHLT report: 984 patients, 4 years period
Cyclosporin use decreased from 40 to 26%
Tacrolimus use increased from 47 to 54%
49. Cardiac allograft vasculopathy
One of the primary causes of graft failure
Risk factors for development in adults: Older donor age, male sex, HT
ISHLT Registry:
60% free of CAV at 11 years post op
Graft survival is 48%: 5 years after diagnosis of CAV
Detection difficult: Variety of presentations
50. Cardiac allograft vasculopathy
Coronary angiography: Gold standard for detection
Stanford classification of CAV:
Type A: Discrete/ focal stenosis
Type B: Lesions with abrupt changes in vessel caliber
Type C: Lesions with diffuse irregular changes+ loss of smaller vessels
ISHLT suggests a grading with % of LMCA stenosis, 2 or more primary vessels or branch
stenosis
In search: Biomarkers for early detection
51. Morbidity + Complications
CAV: Uncertain etiology; but decreased graft survival times
Most likely ethology: Immunologic damage—> Resulting infiltration of coronary
endothelium+ concentric intimal proliferation of smooth muscle cells—> Luminal narrowing
IV USG
Treatment: Immunosuppression, ACE-s, HMG CoA reductase -s
Percutaneous coronary intervention+ Dobutamine stress echo: Limited role
Only definitive treatment: Retransplantation
52. Morbidity + Complications
Rejection during 1st year: Associated with 6% decreased survival during 5 years
Rejection during 1st year: Tacrolimus (27%)< Cyclosporin (42%)
Surveillance for rejection: Endomyocardial biopsy recommended for 6-12 months after
transplant in adolescents
Younger kids: Echo as a screening tool to reduce frequency of biopsy
Treatment regimens: Methylprednisolone, plasmapheresis, Supportive care ( CVVHD,
mechanical cardiac support, mechanical ventilation)
53. Morbidity + Complications
Others:
Renal failure: 10% at 11 years
Requires dialysis
Malignancies (Lymphomas): 15% at 13 years
Reduce immunosuppressive regimens+ Treat EBV aggressively
55. Neurodevelopmental
ISHLT Registry:
3-4% kids aged 0-10 years required total assistance 1 year after transplantation
0.4% kids aged 11-17 years required total assistance at 1 year follow up
56. Results + Outcomes
Younger the patient—> Longer median survival
18.4 y: Infants
16.4y: 1-10 y old
12 y: Adolescents
CM patients: Better outcomes than CHD/ retransplant patients
57. Mortality
1st one month post transplant:
Primary failure, graft failure, MSODs, non- CMV infection, stroke, acute rejection: 80%
After 1 year:
Cardiac allograft vasculopathy, secondary graft failure
Centers performing< 10 transplants/ year: Increased risk of 1 year+ 15 years mortality
59. So summing it up…
Continuous advances + improvements in this field
Current 5y+ 10 y survival of Peds ht transplants parallels adults
Retransplantation continues to have reduced survival outcomes
Donor shortage has prompted ABO incompatible transplants
Future advances in immunosuppressive therapy needed to allow longer survival