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Heart transplantation is an option for patients who have end-stage heart failure, coronary artery disease (CAD), arrhythmias, hypertrophic cardiomyopathy, or congenital heart disease and who remain at risk of death and have intolerable symptoms despite optimal use of drugs and medical devices. Transplantation may also be indicated for patients who cannot be weaned from temporary cardiac-assist devices after MI or nontransplant cardiac surgery and for patients with cardiac sequelae of a lung disorder requiring lung transplantation.
The only absolute contraindication is pulmonary hypertension; relative contraindications include organ insufficiency (eg, pulmonary, renal, hepatic) and local or systemic infiltrative disorders (eg, cardiac sarcoma, amyloidosis).
All donated hearts come from brain-dead donors, who must be < 60 and have normal cardiac and pulmonary function and no history of CAD or other heart disorders. Donor and recipient must have compatible ABO blood type and heart size. About 25% of eligible recipients die before a donor organ becomes available. Left ventricular assist devices and artificial hearts provide interim hemodynamic support for patients waiting for a transplant. However, if left in place too long, these devices put the recipient at high risk of sepsis, device failure, and thromboembolism.
Donor hearts are preserved by hypothermic storage. They must be transplanted within 4 to 6 h. The recipient is placed on a bypass pump, and the recipient heart is removed, preserving the posterior right atrial wall in situ. The donor heart is then transplanted orthotopically (in its normal position) with aortic, pulmonary artery, and pulmonary vein anastomoses; a single anastomosis joins the retained posterior atrial wall to that of the donor organ. Use of an in vitro pump system that modifies cell metabolism in the donor heart and thus may prolong transplant viability > 4 to 6 h is under study.
Immunosuppressive regimens vary but are similar to those for kidney or liver transplantation (eg, anti-IL-2 receptor monoclonal antibodies, a calcineurin inhibitor, corticosteroids).
About 50 to 80% of patients have at least 1 episode of rejection (average 2 to 3); most patients are asymptomatic, but about 5% develop left ventricle dysfunction or atrial arrhythmias. Incidence of acute rejection peaks at 1 mo, decreases over the next 5 mo, and levels off by 1 yr. Risk factors for rejection include younger age, female recipient, female or black donor, and HLA mismatching. Cytomegalovirus (CMV) infection may also influence risk.
Because graft damage can be irreversible and catastrophic, surveillance endomyocardial biopsy is usually done once/yr; degree and distribution of mononuclear cell infiltrate and presence of myocyte injury in specimens are determined. Differential diagnosis includes perioperative ischemia, CMV infection, and idiopathic B-cell infiltration (Quilty lesions). Mild rejection (grade 1) without detectable clinical sequelae requires no treatment; moderate or severe rejection (grades 2 to 4) or mild rejection with clinical sequelae is treated with corticosteroid pulses (500 mg or 1 g daily for several days) and antithymocyte globulin or OKT3 as needed.
The main complication is cardiac allograft vasculopathy, a form of atherosclerosis that diffusely narrows or obliterates vessel lumina (in 25% of patients). Its cause is probably multifactorial and relates to donor age, cold and reperfusion ischemia, dyslipidemia, immunosuppressants, chronic rejection, and viral infection (adenovirus in children, CMV in adults). For early detection, surveillance stress testing or coronary angiography with or without intravascular ultrasonography is often done at the time of endomyocardial biopsy. Treatment is aggressive lipid lowering (see Dyslipidemia : Treatment) and diltiazem; everolimus 1.5 mg po bid may be preventive.
Survival rates at 1 yr are 85 to 90%, and annual mortality thereafter is about 4%. Pretransplantation predictors of 1-yr mortality include need for preoperative ventilation or left ventricular assist devices, cachexia, female recipient or donor, and diagnoses other than heart failure or CAD. Posttransplantation predictors include elevated C-reactive protein and troponin levels.
Most often, death within 1 yr results from acute rejection or infection; after 1 yr, death most often results from cardiac allograft vasculopathy or a lymphoproliferative disorder. Functional status of recipients alive at > 1 yr is excellent; exercise capacity remains below normal but is sufficient for daily activities and may increase over time with sympathetic reinnervation. More than 95% of patients reach New York Heart Association class I cardiac status, and > 70% return to full-time employment.
Drug NameSelect Trade
diltiazemCARDIZEM, CARTIA XT, DILACOR XR
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