Medical Complications of Cardiac Transplant

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1. Cardiac

Ventricular dysfunction

Sinus node dysfunction

Tricuspid regurgitation

Allograft rejection

Allograft coronary artery disease

Decreased exercise tolerance

Infection

Bacterial

Viral

Parasitic

Fungal

Non-cardiac, Non-infectious

Renal insufficiency

Hypertension

Osteoporosis

Hyperlipidemia

Malignancy

Psychologic/behavioral/societal

Glucose intolerance

Pancreaticobiliary disease

Obesity

2. Cardiac Allograft Rejection

Propensity decreases with time

Types

Hyperacute

Acute

Chronic (ACAD)

Cellular

Vascular (Humoral)

Diagnosis

Endomyocardial biopsy

Non-invasive

Clinical

Treatment

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

Grade	Finding	Rejection Severity
0	No infiltrates	None
1A	Focal (perivascular of interstisial infiltrates without necrosis	Mild
1B	Diffuse but not sparse infiltrate without necrosis	Mild
2	One focus only with aggressive infiltrate and/or myocyte damage Focal	Moderate
3A	Multifocal addressive infiltrates and/or myocyte damage	Moderate
3B	Diffuse inflammatory infiltrates with necrosis	Borderline severe
4	Diffuse aggressive polymorphous infiltrate with edema, hemorhage and vasculitis, with necrosis	Severe

Cellular biopsy Cellular biopsy Cellular biopsy Angiogram Vascular biopsy

4. Allograft Coronary Artery Disease

Leading cause of death > 1 year after transplantation

Equivalent to:

"Chronic rejection" in renal allografts

"Vanishing bile ducts" in hepatic allografts

"Bronchiolitis obliterans" in pulmonary allografts

Prevalence of angiographically detectable disease

1 year: 10-2O%

5 years: 30-50%

Potential risk factors

Non-transplant specific

Age

Sex

Family history

Hypertension

Diabetes mellitus

Smoking

Hyperlipidemia

Transplant specific

HLA mismatch, at DR locus

Immunosuppressant drugs

CMV infection

Donor age

Symptomatic

Angina

Acute myocardial infarction

Sudden death

Asymptomatic

Coronary angiography

Nuclear (thallium/sestamibi)

Dobutamine stress echocardiography

Intravascular ultrasound

Vascular Lesion Survival post Angiogram Survival post Transplant Infection post Transplant

5. Infectious Complications

Phases

Early (< 1 month), Nosocomial Phase

Wound

Catheter-related

Hospital acquired pneumonia

Middle (2-5 months), Opportunistic Phase

Toxoplasmosis

Herpes viruses (cytomegalovirus, herpes simplex)

Pneumocystis carinii

Nocardia

Fungi

Late (> 6-12 months) , "Normal" Phase

6. Infectious Prophylaxis

Pathogenic Organism	Prophylactic Agent
Cytomegalovirus	Gancyclovir, Acyclovir, IVIg
Herpes simplex	Acyclovir
Toxoplasmosis	Pyrimethamine and Leucovorin
Pneumocystis	TMP/SMX, Dapsone, Pentamidine
Oral candidiasis	Nystatin, Mycelex troches

Malignancy

7. Malignancy

Incidence 1-2 %/year

Cutaneous Malignancy

Squamous cell carcinoma

Basal cell carcinoma

Lymphoma (PTLD)

Frequency: Most common tumor in cyclosporine-based immunosuppression

Timing: 12-18 months post transplant

Location: Intraabdominal most common

Etiology: B cell origin induced by Epstein-Barr virus

Treatment: Reduce immunosuppression

Acyclovir

Chemotherapy/radiation

8. Cyclosporine-induced Nephrotoxicity

Characteristics

Major decline in renal function in first 6 months

Disproportionate azotemia

Hyperkalemia

Increased uric acid levels

Mild proteinuria

Decreased fractional excretion of sodium

Pathogenesis

Renal vasoconstriction (afferent arterioles)

Prostaglandins

Endothelin

Direct effect on smooth muscle

Direct tubular toxicity

Hypertension and Renal Dysfunction

9. Cyclosporine-induced Hypertension

Incidence: 50-90% of heart transplant recipients

Occurrence: Weeks to months

Treatment goal: BP < 140/90 mmHg

Moderate limitation of salt intake

Maintenance of ideal body weight

Moderate exercise

ACE inhibitors (captopril, enalapril, lisinopril)

Calcium channel blockers (diltiazem, nifedipine, verapamil, amlodipine, and others)

Diuretics

Others (Clonidine, B-blockers, hydralazine, prazocin)

Hyperlipidemia and Diabetes

10. Hypercholesterolemia

Incidence: 60-80% of heart transplant recipients

Occurrence: - 8 months

Magnitude: Increase of 30-80 mg/dl

Positive relationship to:

Prior history of ischemic heart disease

Preexisting lipid abnormalities

Cumulative dose of corticosteroids

Cyclosporine

Treatment goals: Serum cholesterol > 240 mg/Dl (or LDL cholesterol > 160 mg/dl)

Moderate limitation of fat intake

Maintenance of ideal body weight

Moderate exercise

Minimize corticosteroid dose

Gemfibrozil

HMG-CoA reductase inhibitors

Lovastatin

Simvastatin

Pravastatin

Fluvastatin

Bile acid sequestrants (Cholestyramine, Colestipol)

Nicotinic Acid

Probucol

Fish oil (Omega-3 Free Fatty Acids)

11. Osteoporosis

Incidence:

10% of heart transplant recipients

Risk factors:

Corticosteroids

Older age

Lower bone mass before transplantation

Low cardiac output states

Prolonged use of loop diuretics

Physical inactivity

Cardiac cachexia

Heparin administration

Postmenopausal status