prepared for a lecture during the CNE on organ donation at AIIMS raipur

1. Heart Transplantation
Preetam Sahani
MBBS, DNB (Gen. Surgery), MDHM (Osmania Univ.), MCh (CTVS, DU)
Department of Cardiovascular and Thoracic Surgery,
AIIMS, Raipur

3. Pioneering Heart Transplantation… The Stanford group
• Richard Lower
- performed over 250 canine heart transplants and over 800
in humans,
- pioneered the use of cyclosporin to prevent transplant
rejection
- developed a biopsy technique to monitor
rejection
• Norman Edward Shumway
- world's first heart-lung transplant was
performed in 1981, by both Shumway
- The orthotopic technique which became
the standard technique for heart
transplant

4. Cardiac Transplantation…
• Christian Neethling Barnard
• 3rd December 1967
• Groote Schuur Hospital in Cape Town, South
Africa,
• Mortality, POD 18; klebsiella sepsis
• Louis Washkansky received the heart of Denise
Darvall

5. • Barnard (who used Shumway and Lower's research) conducted the
first successful (i.e. not resulting in immediate death) human
transplantation in South Africa on December 3, 1967.
• Adrian Kantrowitz subsequently also conducted a transplant in New
York City on December 6, 1967.
• Shumway performed his first human heart transplantation on January
6, 1968.
• Lower performed his first successful human transplantation in May of
that same year.

6. Heart Transplant in india…
• Prafulla Kumar Sen MD (7 December 1915 – 22 July
1982)
- led the first human heart transplant procedure in India
in 16th feb 1968
* KEM, Mumbai
* patient died of a heart failure after 3
hours
- became the fourth surgeon in the world to
carry out this operation.
- It was also the sixth attempt at this procedure in the
world.
- second heart transplant at KEM, patient survived for16
hours

7. First Successful Heart Transplant in india…
• Dr P. Venugopal along with 20 surgeons
successfully performed India's first heart
transplant at the AIIMS on 3 August 1994
• After the Transplantation of Human Organs Bill
finally received the President’s assent on 7 July
1994

8. Magnitude of the problem…
• India with a 1.2 billion population is lagging behind in OD with a national deceased
donation rate of <1/million population (pmp); however, Tamil Nadu has shown
exemplary performance in OD with 1.3 donor pmp.
• Although India falls in the second position with numbers of live donor transplants
undertaken in the world after the USA, but stand nowhere in the list of deceased
donor transplant
• Country needs 260,000 organs every year, i.e., 180,000 kidneys; 30,000 livers and
50,000 hearts, whereas only 6000 kidneys, 1200 livers and 15 hearts are
transplanted annually (National Organ Transplant Program)
• Solid organ transplant activities are largely driven by the private sector in the
country. The cost of heart transplantation in private sector in India may vary from
rupees fifteen lakhs to forty lakhs depending on the hospital involved
Sachdeva S. Organ donation in India: Scarcity in abundance. Indian J Public Health 2017;61:299-301

9. Heart Transplantation – the Indian perspective
• Today, there are 78 centres in India that do heart transplants. Of these, 44 came
up in the last three years (2015-2017)
• 350 heart transplants were conducted between 1994, when the first heart
transplantation was done in India and 2015
• 300 heart transplantations across India in two years, in the years 2016 and 2017.
- This means there has been a tenfold increase in the number of heart
transplants
• Earlier, transplants were only happening in metro cities like Chennai, Mumbai and
Delhi. But now, even tier two cities like Indore, Jaipur, Aurangabad have emerged
as transplantation hubs,

10. Administrative framework – the indian perspective
• Transplantation of Human Organs Act (THOA) 1994
• Transplantation of Human Organs (Amendment) Act 2011
• Directorate General of Health Services, Government of India implemented the National Organ Transplant
Programme
• Organize…. Promote…..Training…… Protection…… Monitoring
• NOTTO: National Organ and Tissue Transplant Organization: apex centre for all India activities of coordination and
networking for procurement and distribution of organs and tissues and registry of Organs and Tissues Donation and Transplantation in
country - VMMC and Safdarjung Hospital, New Delhi
- policy guidelines and protocols, Network, registry data, Co-ordination,
• ROTTO: Regional Organ and Tissue Transplant Organization
- Seth GS medical college and KEM Hospital, Mumbai (Maharashtra), Govt. Multispecialty Hospital,
Omnadurar, Chennai (Tamil Nadu), Institute of PG Medical Education and Research, Kolkata (West Bengal),
PGIMER Chandigarh(UT of Chandigarh), Guwahati Medical College (Assam)
• SOTTO: State Organ and Tissue Transplant Organization
- envisaged to make 5 SOTTOs in new AIIMS like institutions.

11. The Legal Framework…
• Transplantation of Human Organs Act (THOA) 1994 was enacted to provide a system of removal,
storage and transplantation of human organs for therapeutic purposes and for the prevention of
commercial dealings in human organs.
• source of the organ may be:
- Near Relative donor (mother, father, son, daughter, brother, sister, spouse)
- Other than near relative donor: Such a donor can donate only out of affection and
attachment or for any other special reason and that too with the approval of the authorisation
committee.
- Deceased donor, especially after Brain stem death e.g. a victim of road traffic accident
etc. where the brain stem is dead and person cannot breathe on his own but can be maintained
through ventilator, oxygen, fluids etc. to keep the heart and other organs working and functional.
Other type of deceased donor could be donor after cardiac death.
• Brain Stem death is recognized as a legal death in India after brain stem death almost 37 different
organs and tissues can be donated including vital organs such as kidneys, heart, liver and lungs.

12. • Despite a facilitatory law, organ donation from deceased persons continues to be very poor.
• Transplantation of Human Organs (Amendment) Act 2011 was enacted.
- ‘Near relative’ definition has been expanded to include grandchildren, grandparents.
- Provision of ‘Retrieval Centres’ and their registration for retrieval of organs from deceased donors. Tissue
Banks shall also be registered.
- Provision of Swap Donation included.
- There is provision of mandatory inquiry from the attendants of potential donors admitted in ICU and
informing them about the option to donate – if they consent to donate, inform retrieval centre.
- Provision of Mandatory ‘Transplant Coordinator’ in all hospitals registered under the Act
- To protect vulnerable and poor there is provision of higher penalties has been made for trading in organs.
- Constitution of Brain death certification board has been simplified- wherever Neurophysician or
Neurosurgeon is not available, then an anaesthetist or intensivist can be a member of board in his place,
subject to the condition that he is not a member of the transplant team
- National Organ Transplant Programme with a budget of Rs. 149.5 Crore for 12th Five year Plan
- In pursuance to the amendment Act, Transplantation of Human Organs and Tissues Rules 2014 have been
notified on 27-3-2014

13. Indications for heart transplantation….
• Cardiogenic shock requiring mechanical assistance.
• Refractory heart failure with continuous inotropic infusion.
• NYHA functional class 3 and 4 with a poor 12 month prognosis.
• Progressive symptoms with maximal therapy.
• Severe symptomatic hypertrophic or restrictive cardiomyopathy.
• Medically refractory angina with unsuitable anatomy for revascularization.
• Life-threatening ventricular arrhythmias despite aggressive medical and device
interventions.
• Cardiac tumors with low likelihood of metastasis.
• Hypoplastic left heart and complex congenital heart disease.

14. Selection Criteria for Human Heart Transplantation
• New York Heart Association (NYHA) classification of heart failure III or IV
• Potential for conditioning and rehabilitation after transplant
• Life expectancy (in the absence of cardiovascular disease) is greater than 2 years; and
• No malignancy or malignancy has been completely resected or (upon individual case review) malignancy has been
adequately treated with no substantial likelihood of recurrence with acceptable future risks; and
• Adequate pulmonary, liver and renal function; and
• Absence of active infections that are not effectively treated;
• Absence of uncontrolled HIV infection, defined as:
• CD4 count greater than 200 cells/mm3 for greater than 6 months; and
• HIV-1 RNA (viral load) undetectable; and
• On stable anti-viral therapy greater than 3 months; and
• No other complications from AIDS, such as opportunistic infections (e.g., aspergillus, tuberculosis,
coccidiodomycosis, resistant fungal infections) or neoplasms (e.g., Kaposi's sarcoma, non-Hodgkin's
lymphoma); and
• Absence of active or recurrent pancreatitis; and
• Absence of diabetes with severe end-organ damage (neuropathy, nephropathy with declining renal function
and proliferative retinopathy); and
• No uncontrolled and/or untreated psychiatric disorders that interfere with compliance to a strict treatment
regimen; and
• No active alcohol or chemical dependency that interferes with compliance to a strict treatment regimen.

15. • Patients should receive maximal medical therapy before being considered for
transplantation. They should also be considered for alternative surgical therapies
including CABG, valve repair /replacement, cardiac septalplasty, etc.
• VO2 has been used as a reproducible way to evaluate potential transplant
candidates and their long term risk.
• Generally a peak VO2 >14ml/kg/min has been considered “too well” for
transplant .
• Peak VO2 10 to 14 ml/kg/min had some survival benefit,
• Peak VO2 <10 had the greatest survival benefit.

16. Evaluation of Cardiac Transplantation
Recipient…
• Right and Left Heart Catheterization.
• Cardiopulmonary testing ( VO2 max).
• Labs including BMP, CBC, LFT, UA, coags, TSH, UDS, ETOH level, HIV, Hepatitis
panel, PPD, CMV IgG, RPR / VDRL, PRA (panel of reactive antibodies), ABO and Rh
blood type,lipids.
• CXR, PFT’s including DLCO, EKG.
• Substance abuse history
• Mental health evaluation and social support.
• Financial support.
• Weight no more than 140% of ideal body weight.

17. Contraindications to transplant…
• Systemic illness with a life expectancy 2 y despite HT, including Active or
recent solid organ or blood malignancy within 5 y (eg. leukemia, low-grade
neoplasms of prostate with persistently elevated prostate-specific antigen)
• AIDS with frequent opportunistic infections
• Systemic lupus erythematosus, sarcoid, or amyloidosis that has
multisystem involvement and is still active
• Irreversible renal or hepatic dysfunction in patients considered for only HT
• Significant obstructive pulmonary disease (FEV1 1 L/min)
- Fixed pulmonary hypertension
- Pulmonary artery systolic pressure 60 mm Hg
- Mean transpulmonary gradient 15 mm Hg
- Pulmonary vascular resistance 6 Wood unit

18. Status Listing…
• Once accepted as a transplant candidate, a patient is entered on the list and given a status based upon
severity of illness
• Status I.
• Cardiac Assistance
• Total artificial heart
• Ventricular assist devices
• Intraaotic balloon pump
• Ventilator
• Inotrope dependent for maintaining cardiac output and in the hospital intensive care unit
• Younger than 6 months
• Status II. Patients not status I according to criteria
• Status III. Patients improved and not in immediate need of transplantation or with new complication
making transplantation contraindicated.
• Zones are established to give local priority to recipients within 500 to 1000 mile radius centered on donor
site

19. Heart Donor…
• Brain death is necessary for any cadaveric organ donation.
- defined as absent cerebral function and brainstem reflexes
- with apnea during hypercapnea
- in the absence of any central nervous system depression.
• There should be no hypothermia, hypotension, metabolic abnormalities, or drug
intoxication.
• If brain death is uncertain, confirmation tests using
- EEG,
- cerebral blood flow imaging, or
- cerebral angiography are indicated.

20. Donor criteria…
PREFERABLY UNDER 60 YRS
NORMAL HEART WITH GOOD HAEMODYNAMICS
NO SEPSIS
ABO BLOOD GROUP & WEIGHT COMPATIBILITY WITH RECIPIENT
BRAIN DEAD
APPROPRIATE CONSENT
NORMAL HEART

21. Cardiac Donor – Exclusion Criteria…
• Age older than 55 years.
• Serologic results (+) for HIV, Hepatitis B or C.
• Systemic Infection.
• Malignant tumors with metastatic potential (except primary brain tumors)
• Systemic comorbidity (diabetes mellitus, collagen vascular disease)
• Cardiac disease or trauma
• Coronary artery disease
• Allograft ischemic time estimated to be > than 4-5 hours
• LVH or LV dysfunction on echocardiography
• Death by carbon monoxide poisoning
• IV drug abuse.

22. Donor Evaluation and management…
• Contact local organ procurement organization (OPO).
• Obtain patient’s height and weight.
• Collect CBC, CMP, ABO / Rh testing, HIV, Hepatitis panel, and CMV Ab.
• EKG and Echocardiogram.
• Consider cardiac catheterization if man over 40-45 or woman over 45-50.
• Insert arterial line and right heart catheter
• Donors with beating hearts are often volume depleted because of therapy directed at reducing
cerebral edema.
• As soon as consent for organ transplantation is obtained (usually by OPO), normal saline should
be started or sparingly blood.
• A goal CVP should be 5 to 10 and PCWP of 10 to 16.
• Arterial systolic BP should be maintained at least 100mmHg. If CVP and PCWP are adequate and
hypotension persists dopamine and / or dobutamine should be initiated.

23. • Diabetes Insipidus should be suspected if urine output is >300cc/hr or if hypernatremia begins to develop.
Vasopressin and hypotonic solutions can be used in this setting.
• Electrolytes should be measured and corrected hourly until organ procurement. Hypertension as a result of
sympathetic discharge can be managed with IV NTG.
• Hyperpyrexia or hypothermia should be addressed with surveillance cultures, empiric broad-spectrum
antibiotics, cooling / warming blankets.
• Metabolic acidosis from loss of adrenal and thyroid hormone secretion of brain death can depress myocardial
contractility and cause vasodilatation. Acidosis should be corrected.
• Ventricular dysfunction sometimes responds to levothyroxine 4 micrograms/kg/hr and methylprednisolone
100mg IV qhr and can be tried in this situation. Some recommend empiric treatment with these agents.
• Echo should be performed as soon as possible on the donor heart for assessment of LV function. If
unexpected dysfunction is found in a young person, LVEDD and wall thickness should be measured. If
dimensions are normal then corticosteroid and thyroid replacement should begin and any acidosis should be
corrected. Particular attention should be paid to wall motion abnormalities (especially in individuals with
more advanced age), aortic stenosis, and significant mitral valve abnormalities
• Coronary angiography should be performed on men older than 45 and women older than 50

24. Matching Donor and Recipient…
• Ischemic time during cardiac transplantation is crucial, donor recipient matching
is based primarily not on HLA typing but on the severity of illness, ABO blood
type (match or compatible), response to PRA, donor weight to recipient ratio
(must be 75% to 125%), geographic location relative to donor, and length of time
at current status.
• The PRA is a rapid measurement of preformed reactive anti-HLA antibodies in the
transplant recipient. In general PRA < 10 to 20% then no cross-match is
necessary. If PRA is > 20% then a T and B-cell cross-match should be performed.
• Patients with elevated PRA will need plasmapheresis, immunoglobulins, or
immunosuppresive agents to lower PRA

25. Techniques…
Orthotopic implantation – involves complete explantation of the native heart.
• Biatrial technique: Most common because
the ischemic time is shorter. Complications
include atrial dysfunction due to size
mismatch of atrial remnants and arrhythmia
(sinus node dysfunction, bradyarrhythmias,
and AV conduction disturbances) that
necessitate PPM implantation in 10-20% of
patients.
• Bicaval technique: Decreases incidence of
arrhythmias, the need for a pacemaker, and
risk for mitral or tricuspid regurgitation.
However narrowing of the SVC and IVC make
biopsy surveillance difficult and ischemic
times can be prolonged.

26. Techniques…
• Heterotopic implantation is an alternative
technique in which the donor heart functions in
parallel with the recipient’s heart.
• It accounts of less than 0.3% of heart transplants.
• This procedure can be considered if the donor heart is
small enough to fit into the mediastinum without
physical restriction of function.
• Heterotopic transplantation is beneficial if the patient :
• Has pulmonary hypertension that would exclude
orthotopic transplantation.
• Has heart failure that is potentially reversible
(myocarditis) allowing future removal of the transplant.
• The negative aspects of this approach include:
• A difficult operation.
• No anginal relief.
• Need for anticoagulation (the native heart can cease to
function and thrombose).
• Contraindicated if the native heart has significant
tricuspid or mitral regurgitation.

27. Post Transplant Immunosuppression…
• Primary: Azathioprine/cyclosporine / tacrolimus (utilized in conjuction with
therapeutic drug monitoring)
• Adjunctive: mycophenolate mofetil, Muromonab-CD3 (OKT3), Rapamycin
• Supportive: prednisone (only 20 to 30% centers wean prednisone off if
possible)
• Additive: statins (shown to be immunomodulatory and associated with
improved long term survival

28. Post transplant Management…
• Pneumocystis carinii prophylaxis is started within the first week after transplant.
• If patient or donor is CMV positive then ganciclovir is started on postop day 2.
• Endomyocardial biopsy is performed on postop day 4 and steroids can begin to be tapered if there is no
rejection greater than grade 2b.
• Anticoagulation is started if heterotopic transplantation has been performed.
• Amylase and lipase are measured on day 3 to detect pancreatitis.
• Endomycardial biopsy is performed once a week for the first month and then less frequently depending
on the presence or absence of rejection (usual regimen is qweek x 4 weeks, qmonth x 3 months,
q3months in 1st year, q4months in 2nd year, 1 to 2 times per year subsequently.
• Echocardiography is useful periodically and as an adjunct to endomyocardial biopsy.
• Cardiac catheterization is performed annually for early detection of allograft vasculopathy 2 times per
year subsequently)

29. Complications…
• Rejection
- Hyperacute, Acute, vascular(humoral) rejection.
- Chronic allograft vasculopathy
• Infection
- CMV, Toxoplasmosis, Pneumocystitis, Aspergillosis
• Malignancy
- PTLD, Non Hodgkins lymphoma, Skin malignancies
• Dyslipidemia
• Tricuspid regurgitation

30. Post transplant survival…
• One-year survival after heart transplantation exceeds 80%,
• 10-year survival approaching 60%
• 20-year survival at about 20%
• survival after retransplantation is about 10% lower.
• Ten-year survival is highest in patients with adult congenital heart disease,
followed by patients with cardiomyopathy, valvular heart disease, ischemia, and
retransplantation.
• Survival also depends on age, gender, and other comorbid factors of recipients
and donors.
• Major causes of early death are primary graft failure; rejection; infection;
technical followed later by allograft vasculopathy; lymphomas; other
malignancies; and renal, pulmonary, cerebrovascular, and multi-system failures.

31. Outcomes…
• Poor outcomes are associated with
• Age less than 1 year or approaching age 65.
• Ventilator use at time of transplant.
• Elevated pulmonary vascular resistance.
• Underlying pulmonary disease.
• Diffuse atherosclerotic vascular disease.
• Small body surface area.
• The need for inotropic support pre-transplant.
• Diabetes mellitus.
• Ischemic time longer than 4 hours of transplanted heart.
• Sarcoidosis or amyloidosis as reason for transplant (as they may occur in the
transplanted heart).

32. Donor Heart selection in the modern era…
Khush, Kiran K. “Donor selection in the modern era.” Annals of cardiothoracic surgery vol. 7,1 (2018): 126-134
• The extended criteria donor (ECD) heart, although lacking a unified formal
definition, has traditionally been defined by several risk factors.
- donor age >40 years;
- a history of chest trauma; prolonged hospitalization;
- prolonged cardiopulmary resuscitation or downtime;
- a history of diabetes, tobacco, or illicit drug use;
- transient reversible hypotension;
- short‐term, high‐dose catecholamine administration;
- a substantially smaller weight donor compared with the recipient.
Kobashigawa J, Khush K, Colvin M, et al. Report From the American
Society of Transplantation Conference on Donor Heart Selection in Adult Cardiac Transplantation in the United States. Am J of
Transplant 2017;17:2559-66. 10.1111/ajt.14354

33. Australian surgeons perform first successful 'dead heart' transplants
• 24th October 2014
• St. Vincents Hospital Sydney
• Dr Kumud Dhital
• “heart-in-a-box” concept
organ is kept warm and beating outside the body,
bathed in a special preservative solution rich in
oxygen and nutrients.
• After 20 minutes of cardiac arrest
• Dukes University… North Carolina
- more than 40 transplants
- Transmedics organ care system

34. ISHLT document on Nursing practice for adult heart Tx… (2015)
• Summary of Consensus Statements
- All transplant coordinators should possess a baccalaureate nursing degree, a minimum of 2 years of nursing
experience and clinical certification.
- An international standard of certification for transplant coordinators should be developed.
- A master’s degree in nursing should be required for transplant nurse managers, nurse practitioners and
clinical nurse specialists, noting that a doctorate nursing degree is a future requirement for APN roles in the
USA.
- Staffing ratios, with regard to numbers and mix of roles, depend on inpatient/outpatient case loads
(consensus-recommended staffing levels indicated in).
- Tool development is needed to evaluate acuity of patients in the ambulatory setting to inform adequate
nurse-to-patient ratios.
- Clearer standardized delineation are needed of the roles of the transplant coordinator, nurse practitioner
and clinical nurse specialist.
- Steps should be taken to retain transplant nursing staff, through separate donor call teams, mentorship,
support for advanced degree attainment, engagement in research, flexible hours, and adequate support
from leadership and administration.
- Research is needed to investigate the relationship between nursing ratios/education levels and nursing
satisfaction with patient outcomes.

35. Recommended staffing ratios…(ISHLT 2015)
Number of
patients
evaluated
Optimal number
of RNs per
patients
evaluated
Number of heart
transplant
inpatients
Number of Tx
coordinators
covering heart
inpatient heart
Tx
Number of post-
heart Tx
outpatients
followed
Number of post-
heart Tx
coordinators
following
outpatients
1–10 1 1–15 1 1 to 90 1
11–20 2 16–30 2 For every 90
outpatients add
a nurse
coordinator
For every 90
outpatients add
1 nurse
coordinator
21
+
3 30
+
3

36. .
Thank you
for a patient hearing