Recent advances in managing end-stage heart disease

The cardiac transplant and cardiac assist device programs at Mayo Clinic have been at the forefront in the treatment of end-stage cardiac disease. Featured below are a few of the many innovative approaches pioneered at Mayo Clinic to manage this complex group of patients.

Reducing long-term complications associated with cardiac transplant

Traditional immunosuppressive therapy typically consists of a calcineurin inhibitor (CNI), azathioprine or mycophenolate, and steroids. Although this is an excellent combination for preventing rejection, it does not prevent the long-term complications that occur following heart transplantation, notably the development of cardiac allograft vasculopathy (CAV) and renal dysfunction.

Renal dysfunction is a known complication of CNIs, often causing a progressive decline that can lead to renal failure after transplant. CAV is a progressive coronary disease that affects all the coronary vessels of the transplanted heart and remains the major cause of long-term mortality following transplant.

Several years ago, Mayo Clinic's cardiac transplant program pioneered the use of sirolimus-based immunosuppression in the heart transplant population. In place of a CNI (cyclosporine or tacrolimus), physicians treated transplant patients with sirolimus (rapamycin). This drug is a powerful immunosuppressive, but it also has the additional quality of being an anti-proliferative agent, thereby mitigating some of the adverse effects seen and improving survival.

With sirolimus treatment, renal function improved significantly in all patients. Similarly, the progression of CAV in this patient population has declined and, in a few dramatic cases, has reversed.

Treatment of amyloidosis

Amyloidosis is an infiltrative disease that can affect the heart and eventually lead to a restrictive cardiomyopathy. AL-type (amyloid light chain) amyloidosis is a plasma cell disorder, and severe cardiac involvement carries a poor prognosis, despite advances in chemotherapy. To treat the restrictive cardiomyopathy, cardiac transplantation is performed; this procedure must be followed by bone marrow transplantation to treat the plasma cell abnormality causing the generation of the amyloid protein. Patients receive standard chemotherapy treatment while awaiting transplant.

TTR-type (transthyretin, or familial) amyloidosis is caused by generation of amyloid protein from the liver. Patients with TTR-type amyloidosis who undergo transplant require liver as well as heart transplantation to stop the production of amyloid protein.

During the last 20 years, Mayo Clinic has had the largest experience in the United States in combined transplantation for treatment of amyloidosis, including heart transplant followed by bone marrow transplant for AL amyloidosis, and combined heart and liver transplant for familial TTR amyloidosis.

Treatment of patients with AL amyloidosis is challenging, as they have limited long-term survival compared with nonamyloidosis patients who undergo cardiac transplantation. Thus, this procedure may be helpful in improving short-term survival and, in selected patients, it may be a life-prolonging therapy.

Combined organ transplantation

Mayo Clinic also performs combined organ transplants for indications other than amyloidosis. Patients with coexisting renal failure may be listed for combined heart and kidney transplants. Combined heart-lung transplants are performed in patients with pulmonary hypertension and severe right heart failure, and in those with complex congenital heart disease in whom pulmonary hypertension has developed.

Indications for LVAD

Currently, a left ventricular assist device (LVAD) is used in two situations: as a bridge to transplant or as destination therapy. The LVAD is used to keep the bridge-to-transplant patient alive until transplantation can occur; these patients are usually younger and must be transplant candidates. LVAD therapy allows many patients to resume an almost normal lifestyle until the time of transplant. Currently, about half the patients waiting for transplant at Mayo Clinic are supported by an LVAD.

Destination therapy is typically used in older patients who are not transplant candidates. In these patients, LVAD is used to treat the heart failure, with no plans for transplantation in the future. Usually, because of age and comorbidities, these patients may be frail and severely weakened by heart failure before LVAD implant and thus may have a longer hospital stay and a longer period of rehabilitation before hospital discharge. After rehabilitation, many of these patients are restored to an excellent quality of life with improved mortality.

Treating restrictive cardiomyopathy

In restrictive cardiomyopathy, the heart is small, with thick walls and a small ventricular cavity. LVAD therapy generally has not been used in these patients because the size of the ventricular cavity is not large enough to accommodate the inflow cannula of the LVAD. However, a small number of patients with restrictive cardiomyopathy received LVADs as destination therapy and had reasonable success, in situations where few other options were available.


Mayo Clinic's cardiac transplant program has pioneered the use of innovative immunosuppressive strategies to improve patient survival and comorbidities, and become a world leader in the use of combined organ transplant for difficult conditions such as cardiac amyloidosis. The LVAD program has challenged the accepted paradigms for treating dilated cardiomyopathy and demonstrated the feasibility of, and good outcomes for, the use of LVADs in restrictive heart disease.