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Complications Of Transplantation

Medical Complications of Cardiac Transplant

1. Cardiac

A. Ventricular dysfunction
B. Sinus node dysfunction
C. Tricuspid regurgitation
D. Allograft rejection
E. Allograft coronary artery disease
F. Decreased exercise tolerance
G. Infection
1) Bacterial
2) Viral
3 Parasitic
4) Fungal
H. Non-cardiac, Non-infectious
1) Renal insufficiency
2) Hypertension
3) Osteoporosis
4) Hyperlipidemia
5) Malignancy
6) Psychologic/behavioral/societal
7) Glucose intolerance
8) Pancreaticobiliary disease
9) Obesity

2. Cardiac Allograft Rejection

A. Propensity decreases with time
B. Types
1) Hyperacute
2) Acute
3) Chronic (ACAD)
4) Cellular
5) Vascular (Humoral)
C. Diagnosis
1) Endomyocardial biopsy
2) Non-invasive
3) Clinical
D. Treatment

3. International Society for Heart & Lung Transplantation Endomyocardial Biopsy Grading Scheme

GradeFindingRejection Severity
0No infiltratesNone
1AFocal (perivascular of interstisial infiltrates without necrosisMild
1BDiffuse but not sparse infiltrate without necrosisMild
2One focus only with aggressive infiltrate and/or myocyte damage FocalModerate
3AMultifocal addressive infiltrates and/or myocyte damageModerate
3BDiffuse inflammatory infiltrates with necrosisBorderline severe
4Diffuse aggressive polymorphous infiltrate with edema, hemorhage and vasculitis, with necrosisSevere

4. Allograft Coronary Artery Disease

A. Leading cause of death > 1 year after transplantation
B. Equivalent to:
1) "Chronic rejection" in renal allografts
2) "Vanishing bile ducts" in hepatic allografts
3) "Bronchiolitis obliterans" in pulmonary allografts
C. Prevalence of angiographically detectable disease
1) 1 year: 10-2O%
2) 5 years: 30-50%
D. Potential risk factors
E. Non-transplant specific
1) Age
2) Sex
3) Family history
4) Hypertension
5) Diabetes mellitus
6) Smoking
7) Hyperlipidemia
F. Transplant specific
1) HLA mismatch, at DR locus
2) Immunosuppressant drugs
3) CMV infection
4) Donor age
G. Symptomatic
1) Angina
2) Acute myocardial infarction
3) Sudden death
H. Asymptomatic
1) Coronary angiography
2) Nuclear (thallium/sestamibi)
3) Dobutamine stress echocardiography
4) Intravascular ultrasound

5. Infectious Complications

A. Phases
B. Early (< 1 month), Nosocomial Phase
1) Wound
2) Catheter-related
3) Hospital acquired pneumonia
C. Middle (2-5 months), Opportunistic Phase
1) Toxoplasmosis
2) Herpes viruses (cytomegalovirus, herpes simplex)
3) Pneumocystis carinii
4) Nocardia
5) Fungi
D. Late (> 6-12 months) , "Normal" Phase

6. Infectious Prophylaxis

Pathogenic OrganismProphylactic Agent
CytomegalovirusGancyclovir, Acyclovir, IVIg
Herpes simplexAcyclovir
ToxoplasmosisPyrimethamine and Leucovorin
PneumocystisTMP/SMX, Dapsone, Pentamidine
Oral candidiasisNystatin, Mycelex troches

7. Malignancy

A. Incidence 1-2 %/year
B. Cutaneous Malignancy
1) Squamous cell carcinoma
2) Basal cell carcinoma
C. Lymphoma (PTLD)
1) Frequency: Most common tumor in cyclosporine-based immunosuppression
2) Timing: 12-18 months post transplant
3) Location: Intraabdominal most common
4) Etiology: B cell origin induced by Epstein-Barr virus
5) Treatment: Reduce immunosuppression
6) Acyclovir
7) Chemotherapy/radiation

8. Cyclosporine-induced Nephrotoxicity

A. Characteristics
1) Major decline in renal function in first 6 months
2) Disproportionate azotemia
3) Hyperkalemia
4) Increased uric acid levels
5) Mild proteinuria
6) Decreased fractional excretion of sodium
B. Pathogenesis
C. Renal vasoconstriction (afferent arterioles)
1) Prostaglandins
2) Endothelin
3) Direct effect on smooth muscle
D. Direct tubular toxicity

9. Cyclosporine-induced Hypertension

A. Incidence: 50-90% of heart transplant recipients
B. Occurrence: Weeks to months
C. Treatment goal: BP < 140/90 mmHg
D. Moderate limitation of salt intake
E. Maintenance of ideal body weight
F. Moderate exercise
G. ACE inhibitors (captopril, enalapril, lisinopril)
H. Calcium channel blockers (diltiazem, nifedipine, verapamil, amlodipine, and others)
I. Diuretics
J. Others (Clonidine, B-blockers, hydralazine, prazocin)

10. Hypercholesterolemia

A. Incidence: 60-80% of heart transplant recipients
B. Occurrence: - 8 months
C. Magnitude: Increase of 30-80 mg/dl
D. Positive relationship to:
1) Prior history of ischemic heart disease
2) Preexisting lipid abnormalities
3) Cumulative dose of corticosteroids
4) Cyclosporine
E. Treatment goals: Serum cholesterol > 240 mg/Dl (or LDL cholesterol > 160 mg/dl)
1) Moderate limitation of fat intake
2) Maintenance of ideal body weight
3) Moderate exercise
4) Minimize corticosteroid dose
F. Gemfibrozil
G. HMG-CoA reductase inhibitors
1) Lovastatin
2) Simvastatin
3) Pravastatin
4) Fluvastatin
H. Bile acid sequestrants (Cholestyramine, Colestipol)
1) Nicotinic Acid
2) Probucol
3) Fish oil (Omega-3 Free Fatty Acids)

11. Osteoporosis

A. Incidence:
1) 10% of heart transplant recipients
B. Risk factors:
1) Corticosteroids
2) Older age
3) Lower bone mass before transplantation
4) Low cardiac output states
5) Prolonged use of loop diuretics
6) Physical inactivity
7) Cardiac cachexia
8) Heparin administration
9) Postmenopausal status