CARDIAC TRANSPLANT

CHANGING SCENARIO- DEDICATED HELICOPTER TO TRANPORT DONOR HEARTS

Presenter – Dr.Jyotindra singh MODERATOR- DR.R.C MISHRA

PLAN• INTRODUCTION • HISTORY• PRINCIPLE• INDICATION• INVESTIGATIONS• OPERATIVE TECHNIQUE• COMPLICATION• RESULTS• FUTURE• TAKE HOME MESSAGE

History of Cardiac Transplant• The innovative French surgeon Alexis Carrel performed the first heterotopic

canine heart transplant with Charles Guthrie in 1905.

• Frank Mann at the Mayo Clinic further explored the idea of heterotopic heart transplantation in the 1930s

• In 1946, after unsuccessful attempts in the inguinal region, Vladimir Demikhov of the Soviet Union successfully implanted the first intrathoracic heterotopic heart allograft.

• The first human cardiac transplant was a chimpanzee xenograft performed at the University of Mississippi by James Hardy in 1964.

• South African Christiaan Barnard surprised the world when he performed the first human-to-human heart transplant on December 3, 1967

•

4

The History Of Heart Transplantation

3rd December 1967

Nearly 45 years and 90,000 transplants

Heart in a Box UCLA patient's life-saving donor heart arrives 'warm and beating' inside box - YouTube.flv

History of cardiac transplant• Adrian Kantrowitz performed the first pediatric heart transplant in the world on December 6, 1967 at

Maimonides Hospital in Brooklyn, New York barely 3 days after Christiaan Barnard.

• Over the next several years, poor early clinical results led to a moratorium on heart transplantation, with only the most dedicated centers continuing experimental and clinical work in the field.

• The pioneering efforts of Shumway and his colleagues at Stanford eventually paved the way for the re-emergence of cardiac transplantation in the late 1970s. He is widely regarded as the father of heart transplantation although the world's first adult human heart transplant was performed byChristiaan Barnard in South Africa utilizing the techniques developed and perfected by Norman Shumway & Lower.

• The introduction of transvenous endomyocardial biopsy by Philip Caves in 1973 finally provided a reliable means for monitoring allograft rejection.

• The advent of the immuno-suppressive agent cyclosporine dramatically increased patient survival and marked the beginning of the modern era of successful cardiac transplantation in 1981.

• Heart transplantation is now a widely accepted therapeutic option for end-stage cardiac failure, with more than 2,700 procedures performed annually.

]

Heart In A Box Beating Heart Technology at UCLA could revolutionize field of heart transplantation - YouTube.flv

Cardiac transplant in INDIA• Organ transplantation act in India came in 1994

• Journey of heart transplant program in India began on 3rd August 1994 at All India Institute of Medical Sciences (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

NUMBER OF HEART TRANSPLANTS REPORTED BY YEAR

0

500

1000

1500

2000

2500

3000

3500

4000

4500

1982

1983

1984

1985

1986

1987

1988

1989

1990

1991

1992

1993

1994

1995

1996

1997

1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

Nu

mb

er

of

Tra

ns

pla

nts

Other

EuropeNorth America

ISHLT

Congenital2%

ReTX2%

Myopathy46%

Misc.3%

Valvular3%

CAD44%

1/1982-6/2008

DIAGNOSIS IN ADULT HEART TRANSPLANTS

203040506070

% o

f Cas

es Myopathy CAD

CAD38%

Valvular2%

Misc.4%

Myopathy51%

ReTX3%

Congenital2%

1/2005-6/2008

ISHLT

INDICATIONS• End stage heart disease not amenable to optimal medical or

surgical therapy• Prognosis of 1-yr survival without transplantation <50%

Evaluating criteria

• Low ejection fraction (<20%),• Reduced V O2,max ( 14 mL/kg per minute)• Arrhythmias, high pulmonary capillary wedge pressure (25 mm Hg), • Elevated plasma norepinephrine concentration (600 pg/mL),• Reduced serum sodium concentration ( 130 mEq/dL),• More recently, N-terminal probrain natriuretic peptide (5000 pg/Ml)

INDICATIONS

CHD-INDICATIONS• HLHS• AORTIC STENOSIS WITH LV ENDOCARDIAL

FIBROELASTOSIS• UNBALANCED AV CANAL WITH LV HYPOPLASIA• HLHS EQUIVALENT

TA,D-TGA ,RV & AORTIC HYPOPLASIA

SINGLE VENTRICLE WITH AORTIC HYPOPLASIA

L-TGA WITH SINGLR VENTRICLE & HEART BLOCK

• CARDIAC TUMOURS ( RHABDOMYOMAS,FIBROMAS)• DILATED/RESTRICTIVE/ISCHEMIC CARDIOMYOPATHY• INTRACTABLE ARRHYTHMIAS• FAILED RECONSTRUCTIVE AND PALLIATIVE OPERATIONS

•

Cardiac Donor

• Brain death is necessary for any cadaveric organ donation. This is 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 flow imaging, or cerebral angiography are indicated.

Continuous Heart Transplant Perfusion

"The rush factor will be taken out. I can go all the way to the West Coast to get a heart," said Dr. Bruce Rosengard ofMassachusetts General Hospital who performed the first beating heart transplant in the United Kingdom in 2006.

Matching Donors & Recipients

• Matching is based upon:

• ABO blood group• Body size compatibility (±

20% body weight)• Antibody screen (PRA)• No HLA prospective

matching done unless high levels of pre-formed antibodies on screening (PRA > 10-20%)

• Allocation is determined by:

• Recipient’s priority on waiting list– Status code (1A, 1B, 2)– Time accrued within a status

• Geographic location from donor

Matching Donor and Recipient

• Because 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.

Surgical Transplantation Techniques

• Orthotopic implantation is the most common – it involves complete explantation of the native heart.– Biatrial anastomosis: 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 anastomosis: 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.

Biatrial Technique

Bicaval Technique

Surgical Transplantation 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.

– Hypertopic 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.

Operative technique- Explantation

• Perioperative medications include immunosuppressive agents , antibiotic.

• A median sternotomy is performed.

• The pericardium is opened with a vertical incision extending from the diaphragm to the pericardial reflection at the aorta.

• Aortic cannulation should be high on the lesser curvature,The venae cavae are also cannulated as distally as possible, and umbilical tape snares are placed around the vessels and cannulae.

• The superior vena cava (SVC) and inferior vena cava (IVC) are snared,the aortic cross-clamp is applied, and the patient is placed on bypass and cooled to 32°C.

• The aorta and PA are separated, and the aorta is divided just above the right coronary artery’s origin.

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Heart Transplantation.mp4 - YouTube.flv

EXPLANTATION

• In preparation for a bicaval anastomosis, the atrioventricular groove is opened, and the dissection is extended under the SVC.

• • The right atrium is divided proximally to the SVC, leaving an atrium cuff on the proximal end of the cava

• An incision is made in the left atrial dome below the aorta. The incision is extended counterclockwise across the atrial septum, including the fossa ovalis, to the coronary sinus base.

]

IMPLANTATION

• .The left atrial anastomosis is performed first; the sequence of the other anastomoses can be changed to decrease the ischemic time.

• Donor left atrial cuff is sutured to the recipient left atrium using an extra long 3–0 prolene suture.

• Then, the donor IVC and SVC are anastomosed to the recipient IVC-atrial cuff and SVC-atrial cuff, respectively. This is performed in an en to end manner using 4–0 polypropylene suture.

• The PAs are anastomosed end-to-end using running 4–0 monofilament suture. Again, attention must be paid to avoid constricting or rotating the anastomosis.

• The donor and recipient aortas are anastomosed end-to-end with running 4–0 monofilament suture.

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CPB separation

• May develop bradyarrythmias– Require direct acting sympathomimetics, pacing

• Most grafts recover normal ventricular function– Dysfunction secondary to ischemia– Concern with early recognition of right ventricular failure

• RV failure– PVR > 4 Woods units with little or no reversibility preop– Low CO with elevated CVP (> 15) and elevated PAP (>

40). PCWP may be low.

Management of Right Heart Failure

• Optimize preload – avoid overdistension and underfilling

• Ionotropic & Chronotropic support - milrinone, dobutamine

• Maintain coronary perfusion – vasopressors

• Lower PVR – nitrates, prostaglandins, NO• Mechanical support – IABP, RV assist

device

Other Post-transplant Problems

• Left ventricular failure• Bleeding- higher incidence if anticoagulated

preoperatively for assist devices• Dysrhythmias (bradycardia, AV node dysfunction)

– Pacing and chronotropes for several weeks– 4-7% require permanent pacemaker

• Hypovolemia• Anastamotic obstruction• Hyperacute rejection

– occurs after reperfusion, results from preformed antibodies to donor antigen

The Denervated Heart• Electrical activity cannot cross suture line

– Recipient atrial activity present but not conducted– Donor atrium denervated but source of electrophysiologic

response• Loss of SNS, PNS innervation to donor heart

– Vagal stimulation has no effect on sinus and AV nodes– No reflex tachycardia in response to hypovolemia, hypotension

• ECG has 2 P waves• Indirect sympathomimetic agents have no effect

– Anticholinergics, anticholinesterases, pancuronium, ephedrine• Direct acting sympathomimetics work

– isoproterenol, NE, epi, phenylephrine, dopamine

HETEROTOPIC HEART TRANSPLANTATION

• During heterotopic transplantation, initially performed by Losman and Barnard in 1974, the recipient heart remains in its native location .

• This transplant type may be necessary in situations when there is irreversible high pulmonary vascular resistance or significant donor–recipient size mismatch.

• Greater lengths of SVC, aorta, and PA are harvested.

• The SVC should be harvested to innominate vein level.

• The aortic arch should be harvested along with the proximal aspect of all three head vessels. It is especially important to harvest as much PA as possible to allow a direct donor–recipient anastomosis and avoid the need for a Dacron interposition graft.

• The tissue separating the left pulmonary veins is divided, connecting their orifices and creating a single, large left atrial cuff.

HETEROTOPIC HEART TRANSPLANTATION

• .

• The aortic cannula should be placed as distally as possible in the ascending aorta.

• SVC cannulation is achieved through the right atrial appendage.

• IVC cannulation is performed at the IVC–diaphragmatic junction.

• Venous inflow occlusion is achieved by snaring the SVC and IVC.

• The native heart in the recipient is then cross-clamped.

• The donor heart is placed in the right pleural cavity with the heart’s apex angled to the right.

]

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From: NEJM (2007) 356:e6

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 oversewn, 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.

•

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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

]

Physiologic concerns of Transplant

• Biatrial connection means less atrial contribution to stroke volume.

• Resting heart rate is faster (95 to 110 bpm) and 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.

ADULT HEART TRANSPLANT RECIPIENTS: Relative Incidence of Leading Causes of Death

(Deaths: January 1992 - June 2008)

0

10

20

30

40

50

0-30 Days (N= 3,531)

31 Days – 1Year (N =

3,513)

>1 Year – 3Years (N =

2,716)

>3 Years – 5Years (N =

2,356)

>5 Years – 10Years (N =

5,335 )

>10 Years (N= 3,677)

CAV Acute Rejection

Malignancy (non-Lymph/PTLD) Infection (non-CMV)

Graft Failure

Pe

rce

nta

ge

of

De

ath

s

ISHLT

Postoperative 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.

• ECG’s are obtained qday.

Postoperative Management

• Initiation of medications, particularly immunosuppressive agents begins on the day of the operation. – Cyclosporin started IV on day of the surgery and

usually continued until day 3 at which time converted to po. Usual IV dose is 0.5 mg/kg at 2 mg/min qd

– Azathioprine 2 mg/kg IV qd until day 3 and then converted to po.

– Solumedrol 125mg IV q8h until tolerating po and then Prednisone 0.6 mg/kg/day.

– +/- Muromonab-CD3 (OKT3) started on postop day 1 at 5mg IV qd.

Long-term Management• 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).

• If the donor was CMV positive a Hickman or peripherally inserted central catheter is placed for IV gangciclovir (5mg/kg IV bid x 14 days then 6mg/kg IV qd x 14 days.

• If the recipient was CMV negative then oral acyclovir is admisitered orally. If the recipient is CMV seropositive then the antiviral agent can be discontinued. If seroconversion occurs during treatment (and check at 1, 2, 3, and 6 month intervals), then ganciclovir is initiated for at least an additional 2 week period.

Long-term Management• Cyclosporine levels are checked periodically by

individual center protocols.

• Echocardiography is useful periodically and as an adjunct to endomyocardial biopsy.

• Cardiac catheterization is performed annually for early detection of allograft vasculopathy.

• There is probably no need for routine exercise or nuclear stress testing.

Postoperative Complications

• Surgical – Aortic pseudoaneurysm or rupture at cannulation site– Hemorrhagic pericardial effusion due to bleeding or

coagulopathy• Medical

– Severe tricuspid regurgitation – RV failure

• Pulmonary artery compression

• Pulmonary hypertension – LV failure

• Ischemia • Operative Injury

• Acute rejection

Postoperative Complications

• Rhythm disturbances• Asystole • Complete heart block. • Sinus node dysfunction with bradyarrhythmias (25% permanent but

most resolve within 1-2 weeks).• Atrial fibrillation. • Ventricular tachycardia.

• Coagulopathy induced by cardiopulmonary bypass

• Respiratory failure • Cardiogenic pulmonary edema. • Noncardiogenic pulmonary edema.• Infection.

• Renal or hepatic insufficiency • Drugs. • CHF.

Complications - Rejection

• Avoidance with preoperative therapy with cyclosporin, corticosteroids, and azathioprine.

• If rejection is suspected then workup should include: measurement of cyclosporine level CKMB level, echocardiography for LV function, and endomyocardial biopsy.

• Signs and symptoms of rejection only manifest in the late stages and usually as CHF (rarely arrhythmias).

• Due to close surveillance, most rejection is picked up in asymptomatic patients.

Complications - Rejection

• Hyperacute Rejection: Caused by preforemd antibodies against the donor in the recipient. It occurs within minutes to hours and is uniformly fatal. PRA screening is the best method in avoiding hyperacute rejection.

• Acute Cellular Rejection: Most common form and occurs at least once in about 50% of cardiac transplant recipients. Half of all episodes occur within the first 2 to 3 months. It is rarely observed beyond 12 months unless immunosuppression has been decreased.

Complications - Rejection

• Vascular (humoral) Rejection: not well defined. – Characterized by immunoglobulin and complement in

the microvasculature with little cellular infiltrate. – It is associated with positive cross match,

sensitization to OKT3, female sex, and younger recipient age.

– It is more difficult to treat than acute cellular rejection, is associated with hemodynamic instability, and carries a worse prognosis.

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Rejection

• Invasive surveillance biopsies are the best established method for following patients

• Typically 13-15 biopsies are done in the first year

• Each biopsy requires a minimum of 3 samples from 3 different sites to be meaningful

• A new biopsy grading has been developed for widespread adoption

Endomyocardial Biopsy

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Identifying Allograft RejectionDisease Progression

Alloimmune activation Cellular invasion

Multiple genes and pathways

Cellular inflamationand myocyte necrosis

Graft Dysfunction

Heart failure andarrhythmias

Diagnostic Indicators

Gene Expression ProfilingImmune Function Assays

Endomyocardial Biopsy(intermediate)

Functional Assessment(late)

Staging of Acute Rejection

• If acute rejection is found, histologic review of endomyocardial biopsy is performed to determine the grade of rejection.  

• Grade 0 — no evidence of cellular rejection• Grade 1A — focal perivascular or interstitial infiltrate without

myocyte injury.• Grade 1B — multifocal or diffuse sparse infiltrate without myocyte

injury.• Grade 2 — single focus of dense infiltrate with myocyte injury.• Grade 3A — multifocal dense infiltrates with myocyte injury.• Grade 3B — diffuse, dense infiltrates with myocyte injury.• Grade 4 — diffuse and extensive polymorphous infiltrate with

myocyte injury; may have hemorrhage, edema, and microvascular injury.

Treatment of Acute Rejection• Grade 1A and Grade 1B: No treatment is necessary. • Grade 2: Probably no treatment is necessary. Short course of

steriods (Prednisone 100mg qd x 3 days) is optional.

• Grade 3A and Grade 3B: High dose corticosteroids (Solumedrol 1mg/kg IV). If no response then ATGAM (OTK3 also an option, but causes more intense cytokine reaction).

• Grade 3 with hemodynamic compromise or Grade 4: High dose corticosteriods plus ATGAM or OTK3.

• It is critical that an endomyocardial biopsy be performed to document reversal of rejection after treatment A biopsy is obtained 1 week after initial biopsy showed rejection and then 1 week after therapy complete.

• If ATGAM or OTK3 is used biopsy should be obtained at the end of a course of therapy (usually 7 to 14 days) and then again 1 week later off therapy.

Complications - Rejection

• Allograft vasculopathy (Chronic rejection): Transplant coronary artery disease that is the leading cause of death in patients more than 1 year after transplantation.

• Likely a result of a proliferative response to immunologically mediated endothelial injury (chronic humoral rejection).

• It differs from native CAD in that it is manifested by concentric stenoses, predominately subendocardial location, lack of calcification, can be rapidly progressive and lack of angina pectoris.

• Risk factors include degree of histocompatibility, hypertension, hyperlipidemia, obesity, and CMV infection.

Complications – Rejection Allograft Vasculopathy

• Treatment is mainly prevention with statins, diltiazem, and antioxidant vitamins. Rapamycin is an agent that has shown promise in preventing this complication.

• Treatment with percutaneous interventions and CABG is limited due to its diffuse nature and subendocardial locations.

• Retransplantation for this disorder is an option, but retrospective analysis have shown this approach does not improve mortality as patients do significantly worse with a second transplant as compared with the first.

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Immune FactorsCellular Rejection scoreAntibody –mediated rejectionBalance of Immunosuppression

SMC EC

NonImmune factorsMode of Brain DeathIschemia Reperfusion injuryHyperlipidemiaHypertensionCMV infectionDonor age

Denudinginjury

Nondenudinginjury

PDGF, FGF, IGFTGF-ß, TNF, IL-1

MHC-IIICAM,VCAM

IL-1, IL-2, IL-6, TNFPDGF, FGF, IGF, TGF-ß

Platelets

T-lymphocyte

Macrophage

selectins

INFLAMMATION

Mehra MR. AJT 2006 (in press)

Complications - Infection

• There are two peak infection periods after transplantation:

• The first 30 days postoperatively: nosocomial infections related to indwelling catheters and wound infections.

• Two to six months postoperatively: opportunistic immunosuppresive-related infections.

• There is considerable overlap, however as fungal infections and toxoplasmosis can be seen during the first month.

• It is important to remember that immunosuppressed transplant patients can develop severe infections in unusual locations and remain afebrile.

Opportunistic Infections

• CMV: most common infection transmitted donor to recipient.

• Manifested by fever, malaise, and anorexia. Severe infection can affect the lungs, gastrointestinal tract, and retina.

• If donor is CMV positive and the recipient is CMV negative, prophylaxis with IV ganciclovir or foscarnet is given for 6 weeks and followed by longterm oral prophylaxis with acyclovir.

• If the recipient is CMV positive a less potent regimen can be used.

• Bone marrow toxicity related to treatment can occur and be confused with that due to azathioprine treatment.

Opportunistic Infections

• Toxoplasma gondii: Primary infection can be serious while reactivation is rarely a serious clinical problem.

• Manifested as encephalitis, myocarditis, or pneumonitis. • Treated with pyrimethamine and sulfadiazine.

• Pneumocystis carinii: Prophylactic therapy with TMP/Sulfa is highly effective in preventing progressive bilateral interstitial pneumonia caused by this protozoan.

• Dapsone (Requires G6PD testing) and pentamidine aerosols (does not protect lung apices) are quite effective for those with sulfa allergies.

Opportunistic Infections

• Aspergillus organisms: Invasive Aspergillus infection, typically of the lung or upper respiratory tract is extremely difficult to manage.

• It is fortunately rare, and usually occurs among patients who are severely immunocompromised from use of antilymphocyte antibodies.

• Standard treatment is with IV Amphotericin.

Complications - Malignancy

• Transplant recipients have a 100-fold increase in the prevalence of malignant tumors as compared with age-matched controls.

• Most common tumor is posttransplantation lymphoproliferative disorder (PTLD), a type of non-Hodgkin’s lymphoma believed to be related to EBV.

• The incidence is as high as 50% in EBV-negative recipients of EBV-positive hearts.

• Treatment involves reduction of immunosuppressive agents, administration of acyclovir, and chemotherapy for widespread disease.

• Skin cancer is common with azathioprine use. • Any malignant tumor present before transplantation carries the risk

for growth once immunosuppresion is initiated because of the negative effects on the function of T-cells.

Complications - Hypertension

• As many as 75% of transplant recipients treated with cyclosporine or corticosteroids evential develop hypertension.

• Treatment is empiric with a diuretic added to a calcium channel blocker, B-blocker, or Ace inhibitor.

• If either diltiazem or verapamil is used, the dosage of cyclosporin should be reduced.

Complications - Dyslipidemia

• As many as 80% of transplant recipients eventually have lipid abnormalities related to immunosuppression medications.

• These dyslipidemias have been linked to accelerated allograft arteriopathy.

• These disorders should be treated aggressively with statins and fibrates to hopefully alleviate transplant coronary vasculopathy.

Complications – Tricuspid Regurgitation

• A rare complication is tricuspid regurgitation caused by biotome-induced trauma to the valve apparatus that rarely requires valve replacement.

Hospitalization of Transplanted Patients• If nausea and vomiting prevent administration of oral

medications, the regimen should be changed to an IV one i.e. transplant patients should not be without immunosuppressives for even a short period of time!!!

• Cyclosporin IV dose is 1/3 of oral dose.

• If fever develops then the following should be performed:

• Blood, urine and sputum cultures, BMP, CBC• CXR, Echocardiography (for LV function and effusion).• Consider endomyocardial biopsy for rejection.

RESULTS

• The survival rate according to the United States Scientific Registry for Organ Transplantation reports the 1-year survival rate to be 82% and 3 year survival rate to be 74%.

• The most common cause of mortality was cardiac allograft vasculopathy.

• The UNOS data suggested some group differences with 3-year survival rate for white persons 75%, Hispanics 71%, and African Americans 68%

• Similar survival rates between men and women.• Lowest survival in patients < age 1 and approaching age 65.

RESULTS

• The typical causes of death in the first year are due to acute rejection and infection.

• After the 1st year the primary cause of death is vasculopathy.

• In the later stages (after the perioperative period) arrhythmia may be signs of acute rejection or of an allograft vasculopathy.

RESULTS

• Poor outcomes are associated with the following risk factors:

• 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).

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Heart Transplantation:2012 and Beyond

• Need for improved immunosuppression with less rejection, cardiac allograft vasculopathy and side effects

• Need for better non-invasive methods to detect acute and chronic rejection

• Need to focus on improved survival and quality of life

• Challenges in performing long-term adequately powered multi-centered trials

SOME FAMOUS PERSONALITY• Kelly Perkins climbs mountains around the world to promote positive awareness of organ

donation. Perkins was the first recipient to climb the peaks of Mt. Fuji, Mt. Kilimanjaro,

• Twenty-two years after Dwight Kroening's heart transplant, he was the first recipient to finish an Ironman competition.

• Fiona Coote was the second Australian to receive a heart transplant in 1984 (at age 14) and the youngest Australian. In the 24 years after her transplant she became involved in publicity and charity work for the Red Cross, and promoted organ donation in Australia.

• Race car driver and manufacturer Carroll Shelby received a heart transplant in 1990. Mr Shelby died on May 10, 2012, making him one of the longest living heart recipients.

• Golfer Erik Compton qualified for the PGA Tour at age 32, after his second heart transplant. [

• Former Vice President of the United States Dick Cheney received a heart transplant on March 24, 2012

HELLO– ANY QUESTIONS

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