Michael Bates

Twenty‐Year Survivors of Heart Transplantation at Stanford University

Human heart transplantation started 40 years ago. Medical records of all cardiac transplants performed at Stanford were reviewed. A total of 1446 heart transplantations have been performed between January 1968 and December 2007 with an increase of 1‐year survival from 43.1% to 90.2%. Sixty patients who were transplanted between 1968 and 1987 were identified who survived at least 20 years. Twenty‐year survivors had a mean age at transplant of 29.4 ± 13.6 years. Rejection‐free and infection‐free 1‐year survivals were 14.3% and 18.8%, respectively. At their last follow‐up, 86.7% of long‐term survivors were treated for hypertension, 28.3% showed chronic renal dysfunction, 6.7% required hemodialysis, 10% were status postkidney transplantation, 13.3% were treated for diabetes mellitus, 36.7% had a history of malignancy and 43.3% had evidence of allograft vasculopathy. The half‐life conditional on survival to 20 years was 28.1 years. Eleven patients received a second heart transplant after 11.9 ± 8.0 years. The most common causes of death were allograft vasculopathy (56.3%) and nonlymphoid malignancy (25.0%). Twenty‐year survival was achieved in 12.5% of patients transplanted before 1988. Although still associated with considerable morbidity, long‐term survival is expected to occur at much higher rates in the future due to major advances in the field over the past decade.

Elevation of miR-221 and -222 in the internal mammary arteries of diabetic subjects and normalization with metformin.

Diabetes is a major risk factor for cardiovascular disease and is associated with increased intimal thickening and accelerated vascular smooth muscle cell (VSMC) proliferation. We measured the expression of two microRNAs that promote intimal thickening, miR-221/222, and mRNA encoding a downstream target, p27(Kip1), in internal mammary artery (IMA) segments collected from 37 subjects undergoing coronary artery bypass grafting. The segments were stratified into three groups: non-diabetic subjects (ND), diabetic subjects not on metformin (DMMet-), and diabetic subjects on metformin (DMMet+). The DMMet- group exhibited a significant increase in miR-221/222 and decrease in p27(Kip1) mRNA compared to both the ND and DMMet+ groups. miR-221/222 levels inversely correlated with metformin dose. VSMCs isolated from the IMAs of the DMMet- group proliferate at a faster rate than those of the ND and DMMet+ groups. Further studies into the importance of miR-221/222 in the increased intimal thickening observed in diabetic subjects is warranted.

Pulmonary Resection of Metastatic Hepatocellular Carcinoma After Liver Transplantation

BACKGROUND The primary limitation to long-term survival after liver transplantation for hepatocellular carcinoma (HCC) is tumor recurrence. Pulmonary resection for metastatic HCC prolongs survival in patients after liver resection; this success may be extrapolated to the transplant population in the treatment of pulmonary recurrence of HCC after liver transplantation. METHODS Between January 2000 and January 2006, five patients who underwent orthotopic liver transplantation for HCC were identified on routine follow-up with pulmonary metastases. They all underwent resection of the pulmonary recurrence of HCC and were studied retrospectively. RESULTS The time from transplant to diagnosis of pulmonary recurrence ranged from 150 days to 880 days, with a mean of 500 days. All of the recurrences were amenable to complete resection. Two patients developed a second tumor. One patient had a new primary of squamous cell carcinoma. Another patient had a bony recurrence of HCC in the ninth rib. Four of the patients are still alive, and the fifth died from hepatic failure. The stage of the tumor in the explanted liver ranged from II to IVb. The average time for survival from transplant was 44 months, and the average time from pulmonary resection was 27.5 months. CONCLUSIONS The patients in this study demonstrate survival times similar to patients with HCC treated with liver resection. Although the size of the study population is small, the long survival times in the patients is encouraging. The advanced stage and histologically invasive nature of the primary tumors may predispose to subsequent pulmonary recurrence.

Pacemaker Use Following Heart Transplantation

BACKGROUND The incidence of permanent pacemaker implantation after orthotopic heart transplantation has been reported to be 2%-24%. Transplanted hearts usually exhibit sinus rhythm in the operating room following reperfusion, and most patients do not exhibit significant arrhythmias during the postoperative period. However, among the patients who do exhibit abnormalities, pacemakers may be implanted for early sinus node dysfunction but are rarely used after 6 months. Permanent pacing is often required for atrioventricular block. A different cohort of transplant patients presents later with bradycardia requiring pacemaker implantation, reported to occur in approximately 1.5% of patients. The objectives of this study were to investigate the indications for pacemaker implantation, compare the need for pacemakers following bicaval vs biatrial anastomosis, and examine the long-term outcomes of heart transplant patients who received pacemakers. METHODS For this retrospective, case-cohort, single-institution study, patients were identified from clinical research and administrative transplant databases. Information was supplemented with review of the medical records. Standard statistical techniques were used, with chi-square testing for categorical variables and the 2-tailed t test for continuous variables. Survival was compared with the use of log-rank methods. RESULTS Between January 1968 and February 2008, 1,450 heart transplants were performed at Stanford University. Eighty-four patients (5.8%) were identified as having had a pacemaker implanted. Of these patients, 65.5% (55) had the device implanted within 30 days of transplantation, and 34.5% (29) had late implantation. The mean survival of patients who had an early pacemaker implant was 6.4 years compared to 7.7 years for those with a late pacemaker implant (P<0.05). Sinus node dysfunction and heart block were the most common indications for pacemaker implantation. Starting in 1997, a bicaval technique was used for implantation. The incidence of pacemaker implantation by technique was 2.0% for bicaval and 9.1% for biatrial (P=0.001). Significantly more rejection episodes occurred in the pacemaker group (2.67 ± 2.18) compared with the no-pacemaker group (2.01 ± 2.05) (P<0.05). CONCLUSION Our results show a decreased pacemaker need after bicaval anastomosis and that more patients who needed a pacemaker after transplantation had a pretransplant diagnosis of ischemic cardiomyopathy. In our cohort, the need for a permanent pacemaker was also associated with older donor grafts and an increase in the number of treated rejection episodes.

TRANSCATHETER AORTIC VALVE REPLACEMENT IN END STAGE LIVER DISEASE

Background: Transcatheter aortic valve replacement (TAVR) has emerged as a therapeutic option to treat severe aortic stenosis in high-risk patients. Patients with cirrhosis and end-stage liver disease show high operative morbidity and mortality with cardiac surgery. The Society of Thoracic Surgeons