Cardiac transplantation

Artificial Hearts. Congestive heart failure (CHF) is a common cause of disabiHty and death. It is estimated that three to four million Americans suffer from this condition. Medical therapy in the form of inotropic agents, diuretics (qv), and vasofilators is commonly used to treat this disorder (see Cardiovascularagents). Cardiac transplantation has become the treatment of choice for medically intractable CHF. Although the results of heart transplantation are impressive, the number of patients who might benefit far exceeds the number of potential donors. Long-term circulatory support systems may become an alternative to transplantation (5). 

Calcineurin is involved in cardiac hypertrophy and in cognitive and behavioral defects in the brain. Inhibitors of calcineurin such as cyclosporine A and FK 506 are used clinically in transplant rejection and autoimmune diseases. 

Ischemia-reperfusion damage Stroke (A,l), cardiac failure (A), transplantation (A)... 

Rapamycin has been known for many years to possess immunosuppressive activity by interfering with the activation of B- and T-cells by interleukin-2. Indeed the first clinically approved indication for rapamycin was renal transplantation. Currently, rapamycin and RAD001 also show promise in liver transplantation and cardiac transplantation, respectively. Generally, treatment protocols utilize a combination of an mTORCl inhibitor, a calcineurin inhibitor and steroids to optimize immunosuppression and minimize nephrotoxicity and other side effects. Rapalogs are also... 

The ventricular assist device (VAD) is a surgically implanted pump that reduces or replaces the work of the right, left, or both ventricles. Ventricular assist devices are currently indicated for short-term support in patients refractory to pharmacologic therapies, as long-term bridge therapy (a temporary transition treatment) in patients awaiting cardiac transplant, or in some instances, as the destination therapy (treatment for patients in lieu of cardiac transplant for those who are not appropriate candidates for transplantation).1 The most common complications are infection and thromboembolism. Other... 

Cardiac transplantation is one option for patients with severe heart failure. Candidates for cardiac transplantation generally present with New York Heart Association (NYHA) class III or IV symptoms and have an ejection fraction of less than 25%.1,3 The general indications for cardiac transplantation include rapidly declining cardiac function and a projected 1-year mortality rate of greater than 75%. Mechanical support with an implantable left ventricular assist device may be appropriate while patients await the availability of a viable organ.1,3 Some additional reasons for heart transplant include ... 

Cardiovascular disease has been identified as one of the leading causes of death in organ transplant recipients.55 Posttransplant hypertension (HTN) is associated with an increase in cardiac morbidity and patient mortality in all transplant patients and is also an independent risk factor for chronic allograft dysfunction and loss.56 Based on all the available posttransplant morbidity and mortality data, it is imperative that posttransplant HTN be identified and managed appropriately. 

CXCR4 AMD-3100 AnorMED Phase II Phase I Stem cell transplantation Repair cardiac tissue after myocardial infarction 111, 112 111, 112... 

Yun JJ, Fischbein MP, Laks H, et al. Rantes production during development of cardiac allograft vasculopathy. Transplantation 2001 71(11) 1649-1656. 

Stage D Patients with symptoms at rest despite maximal medical therapy should be considered for specialized therapies, including mechanical circulatory support, continuous intravenous positive inotropic therapy, cardiac transplantation, or hospice care. 

Ventricular assist devices can be used in the short-term (days to several weeks) for temporary stabilization of patients awaiting an intervention to correct the underlying cardiac dysfunction. They can also be used long term (several months to years) as a bridge to heart transplantation. Permanent device implantation has recently become an option for patients who are not candidates for heart transplantation. 

Orthotopic cardiac transplantation is the best therapeutic option for patients with chronic irreversible New York Heart Association Class IV HF, with a 10-year survival of approximately 50% in well-selected patients. 

Cardiac transplantation recipients who develop cardiac valvulopathy... 

Shimizu, K. et al., Host CD40 ligand deficiency induces long-term allograft survival and donor-specific tolerance in mouse cardiac transplantation but does not prevent graft arteriosclerosis, J. Immunol., 165, 3506, 2000. 

Farmer (F3) reported a decrease of Lp(a) after cardiac transplantation, probably as result of decreased Lp(a) synthesis caused by immunosuppressive therapy. 

B3. Barbir, M., Kushwaha, S., Hunt, B., Macken, A., Thompson, G. R., Mitchell, A., Robinson, D., and Yacoub, M., Lipoprotein(a) and accelerated coronary artery disease in cardiac transplant recipients. Lancet 340, 1500-1502 (1992). 

Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Only physicians experienced in immunosuppressive therapy and management of renal, hepatic, or cardiac transplant patients should use mycophenolate. Manage patients receiving the drug in facilities equipped and staffed with adequate laboratory and supportive medical resources. The physician responsible for maintenance therapy should have complete information requisite for the follow-up of the patient. 

Renal, cardiac, and hepatic transplant Mycophenolate is indicated for the prophylaxis of organ rejection in patients receiving allogeneic renal, cardiac, or hepatic transplants. Use mycophenolate concomitantly with cyclosporine and corticosteroids. 

Give the initial oral dose as soon as possible following renal, cardiac, or hepatic transplantation. It is recommended that mycophenolate be administered on an empty stomach. In stable renal transplant patients, mycophenolate may be administered with food if necessary. 

Cardiac transplantation 1.5 g twice a day administered orally (daily dosage of 3 g). 

Elderly- 1 g twice a day for renal transplant patients, 1.5 g twice a day for cardiac transplant patients, and 1.5 g twice a day in hepatic transplant patients. 

Mycophenolate may be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks. 

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