Heart transplantation

1. Heart Transplantation
Where is world now ?

2. History Brief
Heart transplantation became a reality in the late 1960s after nearly a half of a century of
research in surgical techniques, pathophysiology, and immunology by Drs. Richard Lower
and Norman Shumway. Dr. Shumway is regarded as the father of heart transplantation. Dr.
Christiaan Bernard, a student of Lower, performed the first heart transplantation in the
laboratory on December 3, 1967. Dr. Adrian Kantrowitz performed the first pediatric
transplant on Dec 6, 1967 in New York. He also laid the foundation for formulating the
brain death criteria, which later came out of the Ad Hoc Committee of the Harvard Medical
School. The early results were quite dismal, and many centers were forced to close their
programs. In the late 1970s, survival improved to six years. Major advances in survival
should be credited to Dr. Margaret Billingham for standardization of pathological diagnosis
of rejection and later development of anti-rejection medicines. In 1983, the U.S. Food and
Drug Administration (FDA) approved cyclosporin after its discovery by the Sandoz team. In
October 1994, ventricular assist devices (VADs) were approved for supporting patients to
transplant (bridge to transplantation [BTT]). In October 2014, Dr. Kumud Dhital of Australia
transplanted a heart that was resuscitated after cardiac death of the donor, opening a new
door to increasing the number of organs.

3. Clinicopathological Stages
Stages Description
A Patients at high risk (e.g., with hypertension, atherosclerotic disease, diabetes mellitus,
metabolic syndrome, cytotoxin, family history) for HF but without structural heart
disease or symptoms of HF
B Patients with structural heart disease (e.g., left ventricular [LV] dysfunction) but
without symptoms of HF
C Patients with structural heart disease with prior or current symptoms of HF
D Patients with refractory HF requiring specialized interventions

4. NYHA CLASS
NYHA Description
I Asymptomatic or symptomatic only at activity levels that would limit normal individuals
II Symptomatic with ordinary exertion (e.g., 2 city blocks or 1 flight of stairs in a faster than usual
pace)
III Symptomatic with less than ordinary exertion (e.g., less than 2 city blocks or 1 flight of stairs)
IV Symptomatic at rest

5. Parameters Systolic (HFREF) Diastolic (HFpEF)
History
Coronary artery disease +++ ++
Hypertension ++ ++++
Diabetes ++ ++
Valvular heart disease ++++ +
Paroxysmal dyspnea ++ +++
Physical Examination
Cardiomegaly +++ +
Soft heart sounds ++++ +
S 3 gallop +++ +
S 4 gallop + +++
Hypertension ++ ++++
Mitral regurgitation +++ +
Rales ++ +
Edema +++ +
Jugular venous distention +++ +
Chest Radiograph
Cardiomegaly +++ +
Pulmonary congestion +++ +++
Electrocardiogram
Left ventricular hypertrophy ++ ++++
Q waves ++ +
Low voltage +++ -
Echocardiogram
Left ventricular hypertrophy ++ ++++
Left ventricular dilation ++ -
Left atrial enlargement ++ ++
Reduced ejection fraction ++++ -

6. History of Cardiac Transplant
1905- Alexis Carrel & Charles Guthrie -First heterotopic
canine heart TX
1930-Frank Mann- heterotopic heart transplantation at
Myo clinic
1946- unsuccessful attempts in the inguinal region, Vladimir
Demikhov of the Soviet Union successfully implanted the
first intrathoracic heterotopic heart allograft.
1964-The first human cardiac TX - a chimpanzee xenograft
performed at the University of Mississippi by James Hardy
1967-South African Christian Barnard -first human-to-
human heart transplant

7. Cardiac transplant in INDIA
Organ transplantation act – 1994
 Heart transplant program - 3rd August 1994 at AIIMS,
New Delhi.
So far only about 70 heart transplants have been
conducted across the country, out of which 26 have been
performed at the All India Institute of Medical Sciences
alone.
 The cost of heart transplant surgery in India is anywhere
between 8 lakhs to 10 lakhs and the monthly cost of
immunosuppressant drugs is 15,000 to 20,000.
Hyderabad first transplant was done in global hospital
3 heart transplants have been done in NIMS

8. HETEROTOPIC HEART TRANSPLANTATION
 The left atrial anastomosis is performed first using
3–0 monofilament polypropylene suture, attaching
the donor left atrium to the incision in the recipient
left atrium
The recipient’s SVC is opened with a vertical
incision, and the anastomosis is performed
attaching the donor SVC to the recipient SVC
The aortic anastomosis is performed using 4–0
monofilament suture in an end-to-side manner
Either the right or left PA branch is over sewn, with
the other participating in the anastomosis with the
donor PA
 A prosthetic graft may be required if the donor PA
length is not adequate.

9. BICAVAL VS STANDARD TECHNIQUE
A biatrial anastomosis results in an abnormally enlarged atrial cavity
and distorted atrial geometry, producing atrioventricular (AV) valvular
insufficiency . Additionally, bradyarrhythmias may arise because of the
close proximity of the right atrial suture line to the sinus node,
resulting in node injury
Yacoub and Banner modified the standard technique described by
Lower and Shumway . A bicaval approach preserves the donor atria
and combines the standard left atrial anastomosis with a separate
bicaval anastomosis
Another approach is total orthotopic heart transplantation. This
approach was described by Webb and Neely in 1959 and introduced
by Dreyfus and Yacoub in 1991 .
It involves complete recipient atrial excision with complete AV
transplantation, in addition to separate
Bicaval and pulmonary venous anastomoses . This technique’s major
disadvantages are the additional time required to complete the six
anastomoses and the technical challenge of performing the
pulmonary vein island anastomoses

10. Physiology of Transplant
Biatrial connection means less atrial contribution to stroke volume.
Resting heart rate is faster-95 to 110 bpm
 acceleration of heart rate is slower during exercise because of
denervation
Diurnal changes in blood pressure are abolished
Diastolic dysfunction is very common because the myocardium is stiff
from some degree of rejection and possibly from denervation.

11. Surgery for heart failure
• CABG
• Valve replacement
• Left ventricular reconstruction
• Passive cardiac support devices
• Heart transplantation

12. Heart transplant
• Evaluation of the potential recipient
• The cardiac donor
• Surgical considerations
• Immunosuppression
• Rejection
• Medical complications and comorbid conditions
• Malignant Neoplasia
• Diabetes
• Hypertension
• Hyperlipidaemia
• Cardiac Allograft Vasculopathy
• Outcomes after Heart Transplantation Survival
• Functional Outcomes

13. Care of Heart Transplant Patients After Surgery
Short- and long-term management of cardiac transplant patients
involves cardiac support, as well as monitoring and treatment of
rejection, infection, and malignancies. Organ rejection presents itself as
hyperacute, acute cellular or acute antibody-mediated rejection.
Hyperacute rejection occurs within minutes to hours due to binding of
preformed antibodies to donor antigens leading to complement
fixation in vessels and tissue death. Acute cellular rejection is more
common in the first six months occurring in 20-40%. It is T cell-
mediated against the donor's human leucocyte antigen (HLA). Acute
antibody-mediated rejection occurs in about 10% usually due to
antibodies driven by T cells to donor vascular antigens.

14. Care of Heart Transplant Patients After Surgery
This leads to B cell activation and production of plasma cells. It is
difficult to diagnose but usually associated with detection of
immunoglobulins, complement fragments, CD 68 positive cells, and de
novo anti-HLA antibodies. Surveillance endomyocardial biopsies are
essential in the first year to detect rejection at the subclinical level
before the development of cardiac dysfunction.4 Infants and children
have lower rejection rates while adolescents have higher rates. Any
symptoms after heart transplant need to be assumed to be due to
rejection. There are several adjunct noninvasive measures under
investigation based on electrophysiology, magnetic resonance imaging,
biochemical markers, and gene expression profiling.

15. Care of Heart Transplant Patients After Surgery
The introduction of mycophenolate mofetil (MMF), tacrolimus, cyclosporine
microemulsion, sirolimus, rapamycin protein inhibitors, new generation
monoclonal antibodies ( anti-interleukin-2 receptor antagonists, daclizumab,
basilix-imab, alemtuzumab), OKT3, and the depleting polyclonal biologic
thymoglobulin has significantly increased the ability of physicians to fight
rejection.However, there is a price to pay in the form of increased infections
and malignancies. The problem of intimal and smooth muscle proliferation
leading to graft vessel disease remains unresolved. Recent advances in
therapy have been minimal except for drug minimization protocols leading to
reduction of corticosteroid and calcineurin inhibitors. At the same time, the
advances in the management of allosensitization are noteworthy. The
crossmatch prevents transplanting in the presence of donor-specific
antibodies. Panel reactive antibody (PRA) screening is done in all heart
transplant candidates, and further evaluation is needed if PRA levels are
elevated above 10%.

16. Care of Heart Transplant Patients After Surgery
• The factors involved leading to sensitization are homograft use in
congenital surgery, female sex, prior pregnancies, black race, VAD surface
exposure, retransplantation, perioperative blood products usage, and
infections. It is diagnosed by measuring PRAs. PRA levels greater than 10%
are treated, and aggressive desensitization with plasmapheresis,
intravenous immunoglobulin (IVIG), and rituximab is associated with
significantly improved survival. IVIG is used to neutralize preformed
antibodies before and after transplantation. The effectiveness is variable.
Plasmapheresis is fast, short-lived, and can be done immediately before
transplantation. Rituximab (anti-CD20) is frequently used and is effective in
the long term. Immunoabsorbtion and spelenectomy are rarely used.The
rate of infection is very high with these therapies. Because of their
immature immune systems, infants can have ABO incompatible organs. The
limit of isohemagglutinins titer that makes this possible is not determined.

17. STICH TRIAL

18. STICH TRIAL

19. Surgery for Management of Heart Failure (HF):
Guideline Recommendations (ESC-2012)

20. Kaplan-Meier estimates of death from any cause in patients with moderate to severe MR at baseline assigned to receive
medical therapy (MED) alone or MED plus CABG who did or did not undergo mitral valve procedures. MVR, mitral valve repair.
(From Deja MA, Grayburn PA, Sun B, et al: Influence of mitral regurgitation repair on survival in the surgical treatment for
ischemic heart failure trial. Circulation 125:2639, 2012.)

21. Surgical ventricular repair

22. Candidate selection Heart transplantation

23. Kaplan-Meier cumulative 1-year survival of recipients in the derivation cohort (A) and validation cohort (B) as stratified by
three-point increments of risk in the IMPACT score used to predict risk of death for patients undergoing orthotopic heart
transplantation. (From Weiss ES, Allen JG, Arnaoutakis GJ, et al: Creation of a quantitative recipient risk index for mortality
prediction after cardiac transplantation (IMPACT). Ann Thorac Surg 92:914, 2011.)

24. Modified from Stewart S, Winters GL, Fishbein MC, et al: Revision of the 1990 working formulation for the standardization of
nomenclature in the diagnosis of heart rejection. J Heart Lung Transplant 24:1710, 2005.

25. Modified from Stewart S, Winters GL, Fishbein MC, et al: Revision of the 1990 working formulation for the standardization of
nomenclature in the diagnosis of heart rejection by antibody mediation. J Heart Lung Transplant 24:1710, 2005.

26. Modified from Hertz MI, Aurora P, Christie JD, et al: Registry of the International Society for Heart and Lung
Transplantation: a quarter century of thoracic transplantation. J Heart Lung Transplant 27:937, 2008.
• Types of Malignant Neoplasia,
with Cumulative Prevalence,
Reported after Heart
Transplantation

27. Kaplan-Meier survival after report of cardiac allograft Vasculopathy (CAV) within 3 years of transplant
and survival in patients without CAV by era.(From Stehlik J, Edwards LB, Kucheryavaya AY, et al: The
registry of the International Society for Heart and Lung Transplantation: 29th official adult heart
transplant report—2012. J Heart Lung Transplant 31:1052, 2012.)

28. Kaplan-Meier adult heart transplant survival in first-time recipients by era, showing a 10-year survival rate of at least 50%
and an improvement in survival by era. (From Stehlik J, Edwards LB, Kucheryavaya AY, et al: The registry of the
International Society for Heart and Lung Transplantation: 29th official adult heart transplant report—2012. J Heart Lung
Transplant 31:1052, 2012.)

29. Future of stage-D heart failure
The most widely used surgical procedure for heart failure is
CABG[STICH]
Drop in operative/post op mortality with surgery
VAD
 TAVR
 Of course heart transplantation in developing heart

30. Achievement till now
One-year survival after heart transplantation exceeds 80%, with 10-
year survival approaching 60% and 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. Latest news
• The world’s first transplant of a “dead heart” has taken place in
Australia, where doctors say that the surgical technique could
significantly increase the number of potential donor
organs………………….http://www.independent.co.uk/news/science/aus
tralian-surgeons-perform-first-successful-dead-heart-transplants-
9816729.html

32. Dedicated readers ,patients and their relatives
http://www.acc.org/latest-in-
cardiology/articles/2015/05/26/1
1/51/heart-transplantation-the-
present-and-future?w_nav=CI