Combined organ transplantation a viable therapeutic solution for patients with dual vital organ failure
Following the reports of the first simultaneous combined heart and kidney transplantation (CHKTx) in 1978 and combined heart and liver transplantation (CHLTx) in 1985, both have become viable therapeutic solutions in the treatment of dual vital organ failure.
Since 1987, reports to the United Network for Organ Sharing (UNOS) indicate that CHKTx has been performed in 910 patients through Oct. 31, 2013, and through Oct. 31, 2013, CHLTx was performed in 143 patients at 34 centers (only 15 centers with more than two cases). Through Oct. 31, 2013, combined heart, liver and kidney transplantation was reported in only 13 patients.
The Heart Transplantation Program at Mayo Clinic in Rochester, Minnesota, started in June 1988. More than 500 heart transplantations have been performed to date. Included in those transplantations:
- 60 transplants (12 percent) were multiple organ transplants involving the kidney, liver or both
- 30 were CHKTx procedures
- 26 were CHLTx procedures
- 4 were combined heart-liver-kidney transplants
Each of these series represents the largest collection of such procedures performed by a single institution. The frequency of these multiple organ transplants has increased over time: 55 of the 64 procedures have been performed since 2000.
Furthermore, of the 102 patients currently on the heart transplant waiting list:
- 17 are listed for multiple organs
- 12 are listed for combined heart-liver
- 5 are listed for combined heart-kidney
Additionally, combined heart-lung and heart-lung-liver transplantations have been performed in a few instances, but are not included in this update.
Overall survival after heart transplantation alone at Mayo Clinic since 1988 is 93 percent at one year, 81 percent at five years and 65 percent at 10 years.
Over the same time period, the Mayo outcomes were superior to survival reported by UNOS and the International Society for Heart and Lung Transplantation (ISHLT) at one year (UNOS: 89 percent; ISHLT: 82 percent) and three years (UNOS: 80 percent; ISHLT: 75 percent).
Combined heart-liver transplantation
The most common indication for CHLTx is familial amyloidosis (FA), a fatal autosomal dominant disease caused by deposition of an abnormal mutant protein, transthyretin. FA is associated with progressive peripheral and autonomic neuropathy and dysfunction of the cardiac, gastrointestinal and urinary systems. The prognosis for symptomatic cardiac amyloidosis is poor.
The worldwide experience of CHLTx is limited, and fewer than 15 cases have been reported in the literature, of which 11 were performed for FA. The experience at Mayo Clinic — 26 CHLTx procedures — exceeds that found in the world literature. FA was the indication for CHLTx in 18 patients, and indications for the other four CHLTx procedures were hemochromatosis, restrictive cardiomyopathy, congenital heart disease and primary pulmonary hypertension; the last three of these patients had advanced cirrhosis due to chronic congestive heart failure.
Median waiting time for patients with FA who underwent CHLTx at Mayo Clinic was 201 days (range, 45 to 443 days). Currently, 12 patients are alive at a mean time of 4.3 years (maximum, 13 years) after CHLTx, and two patients have survived five and eight years after combined heart-liver-kidney transplantation performed for the indication of FA.
One major issue in the long-term follow-up of these patients is progression of peripheral neuropathy, which is part of the clinical spectrum of FA; the extent of neuropathy must be considered during evaluation for CHLTx. Of the 12 late survivors after CHLTx performed for FA at Mayo Clinic, five had evidence of progressive neuropathy.
Importantly, survival rates at one month, one year, five years and 10 years after CHLTx were comparable to survival rates after both isolated heart transplant and isolated liver transplant. Interestingly, freedom from cardiac allograft rejection was significantly higher at 10 years (P = 0.02) after CHLTx (83 percent) compared with that after isolated heart transplant (32 percent).
Combined heart-kidney transplantation
Chronic kidney disease following cardiac transplantation is a major source of morbidity and mortality. When patients present with extensive coexisting cardiac and renal disease, the presence of severe, irreversible renal dysfunction is a contraindication for isolated heart transplant.
CHKTx has become an accepted treatment option for patients with this challenging clinical scenario. Success has been documented after simultaneous or staged CHKTx. The criteria for consideration of combined organ transplant include a glomerular filtration rate (measured using iothalamate clearance corrected for body surface area) less than 40 mL/min, despite hemodynamic optimization. All 30 CHKTx procedures performed to date at Mayo were done as a simultaneous procedure; two were done for FA.
Postoperatively, intensive care unit and hospital stay did not differ significantly between Mayo Clinic's CHKTx patients and those undergoing isolated heart transplantation. Two early deaths occurred, and late survival for hospital survivors was 100 percent at follow-up extending to five years. Early cardiac allograft dysfunction was present in two patients, but late cardiac allograft function was normal in all patients. Four patients had delayed kidney allograft function, necessitating temporary dialysis, and one of these went on to have permanent graft dysfunction.
Survival rates for CHKTx recipients were similar to those achieved after isolated heart transplantation. Similar to the observations after CHLTx, the incidence of cardiac rejection was less frequent after CHKTx than after isolated heart transplants. Although the time to first rejection did not differ significantly, one year after transplantation rejection episodes were virtually absent in CHKTx recipients but were still present in isolated heart transplant recipients.
The success of Mayo Clinic's program is owed to the strong collaboration of a wide multidisciplinary group that participates in preoperative selection and optimization, surgical procedure, postoperative care, and long-term follow-up.
Points to remember
- Approximately 12 percent of all heart transplantation procedures performed at Mayo Clinic in Rochester, Minnesota, since 1988 were combined with simultaneous liver (n = 26) or kidney (n = 30) transplantation and, in some instances, both (n = 4).
- Almost 20 percent of all patients currently awaiting heart transplants at Mayo Clinic are listed for combined organ transplants. This is consistent with our observation that the frequency of combined organ transplants has significantly increased in the past decade, especially in the past five years.
- Late survival after combined organ transplantation is similar to that after isolated heart transplantation, and freedom from cardiac allograft rejection and dysfunction is improved following combined organ transplantation compared with isolated heart, liver or kidney transplantation.