A prospective, randomized trial of single-drug versus dual-drug immunosuppression in heart transplantation: the tacrolimus in combination, tacrolimus alone compared (TICTAC) trial.

BACKGROUND: Cardiac transplantation, a procedure nearly abandoned in the 1970s, has evolved into the standard of care for appropriate patients with end-stage heart failure. Much of this success has been due to improvements in immunosuppression, including the introduction of a triple-drug regimen. Retrospective reports suggested that single-drug immunosuppression with tacrolimus was feasible. As such, a prospective, randomized trial was conducted to test this approach. METHODS AND RESULTS: One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70 ± 0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65 ± 0.40 (95% confidence interval, 0.55 to 0.74; P=0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P=0.58, log-rank). CONCLUSIONS: Addition of mycophenolate to single-agent immunosuppression did not provide an advantage over single-agent immunosuppression in terms of rejection, allograft vasculopathy, or 3-year survival. Corticosteroids, which have traditionally been a mainstay of therapy, were successfully discontinued in all patients. These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00299221.

Simple method to eliminate interference between ventricular assist devices and cardiac rhythm devices.

BACKGROUND: Report on a simple solution to allow programming of defibrillators in the presence of a Heartmate II (Thoratec Corporation, Pleasanton, CA, USA) ventricular assist device. Ventricular assist devices have become increasingly utilized for patients waiting for heart transplantation as well as those who will be maintained on a permanent support. The Heartmate II, which was recently given Food and Drug Administration approval as a bridge-to-transplant device, has a particular anomaly that complicates patient management. The pulse width modulator of the Heartmate II produces electromagnetic noise that interferes with the ability to interrogate and program certain defibrillators, and explantation of the defibrillator has been reported as the only viable solution. METHODS: The authors describe the use of cast-iron pans to reduce the electromagnetic interference between St. Jude Medical's first-generation Atlas family of defibrillators (St. Jude Medical, St. Paul, MN, USA) and the Heartmate II pump. RESULTS: The use of a simple shielding protocol avoids the need to remove a pre-existing defibrillator from a patient receiving support from the Heartmate II ventricular assist device. CONCLUSIONS: The method described herein is important as future generations of medical devices may present different types of device-device interactions. Simple bedside methods to eliminate interference can potentially help patients who would otherwise need one or another device removed.

Randomized trial of tacrolimus monotherapy: tacrolimus in combination, tacrolimus alone compared (the TICTAC trial).

BACKGROUND: Prior retrospective studies have suggested that tacrolimus monotherapy is an option associated with excellent outcomes and reduced toxicities. METHOD: We conducted a prospective, randomized, 2-center study of tacrolimus combination therapy vs monotherapy. From April 16, 2004, to September 15, 2005, 58 adult heart transplant patients were studied. All received oral tacrolimus, mycophenolate mofetil, and corticosteroids. Patients were then randomized to a group where mycophenolate was maintained (COMBO) or to a group where it was discontinued (MONO) 14 days post-transplant. Corticosteroids were rapidly withdrawn in both groups between 8 and 12 weeks. RESULT: The primary end point (mean 6-month International Society of Heart and Lung Transplantation biopsy score) was 0.44 +/- 0.04 in the MONO group and 0.60 +/- 0.05 in the COMBO group (p = 0.013, unpaired Student's t-test). The freedom from rejection grade of 2R or higher at 6 and 12 months was 93.3% with MONO and 92.9% with COMBO (p = NS). CONCLUSION: Tacrolimus monotherapy appears to be safe and efficacious in heart transplant recipients and is not associated with excess rejection in the first year post-transplant. Further studies of this approach are warranted.