Use of Anti-Thymocyte Globulin for Induction Therapy in Cardiac Transplantation: A Review.

The most common causes of death after heart transplantation (HTx) include acute rejection and multi-organ failure in the early period and malignancy and cardiac allograft vasculopathy (CAV) in the late period. Polyclonal antibody preparations such as rabbit anti-thymocyte globulin (ATG) may reduce early acute rejection and the later occurrence of CAV after HTx. ATG therapy depletes T cells, modulates adhesion and cell-signaling molecules, interferes with dendritic cell function, and induces B-cell apoptosis and regulatory and natural killer T-cell expansion. Evidence from animal studies and from retrospective clinical studies in humans indicates that ATG can be used to delay calcineurin inhibitor (CNI) exposure after HTx, thus benefiting renal function, and to reduce the incidence of CAV and ischemia-reperfusion injury in the transplanted heart. ATG may reduce de novo antibody production after HTx. ATG does not appear to increase cytomegalovirus infection rates with longer prophylaxis (6-12 months). In addition, ATG may reduce the risk of lymphoproliferative disease and does not appear to confer an additive effect on acquiring lymphoma after HTx. Randomized, controlled trials may provide stronger evidence of ATG association with patient survival, graft rejection, renal protection through delayed CNI initiation, as well as other benefits. It can also help establish optimal dosing and patient criteria to maximize treatment benefits.

Combined Heart and Kidney Transplantation: A 23-Year Experience.

BACKGROUND: We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. METHODS: From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. RESULTS: The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). CONCLUSIONS: The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

Similar Mortality and Morbidity of Orthotopic Heart Transplantation for Patients 70 Years of Age and Older Compared With Younger Patients.

BACKGROUND: The upper age limit of heart transplantation remains controversial. The goal of the present study was to investigate the mortality and morbidity of orthotopic heart transplantation (HT) for recipients ≥70 compared with those <70 years of age. METHODS: Of 704 adults who underwent HT from December 1988 to June 2012 at our institution, 45 were ≥70 years old (older group) and 659 were <70 years old (younger group). Survival, intraoperative blood product usage, intensive care unit (ICU) and hospital stays, and frequency of reoperation for chest bleeding, dialysis, and >48 hours ventilation were examined after HT. RESULTS: The older group had 100% 30-day and 60-day survival compared with 96.8 ± 0.7% 30-day and 95.9 ± 0.8% 60-day survival rates in the younger group. The older and younger groups had similar 1-year (93.0 ± 3.9% vs 92.1 ± 1.1%; P = .79), 5-year (84.2 ± 6.0% vs 73.4 ± 1.9%; P = .18), and 10-year (51.2 ± 10.7% vs 50.2 ± 2.5%; P = .43) survival rates. Recipients in the older group had higher preoperative creatinine levels, frequency of coronary artery disease, and more United Network for Organ Sharing status 2 and fewer status 1 designations than recipients in the younger group (P < .05 for all). Pump time and intraoperative blood usage were similar between the 2 groups (P = NS); however, donor-heart ischemia time was higher in the older group (P = .002). Older recipients had higher postoperative creatinine levels at peak (P = .003) and at discharge (P = .007). Frequency of postoperative complications, including reoperation for chest bleeding, dialysis, >48 hours ventilation, pneumonia, pneumothorax, sepsis, in-hospital and post-discharge infections, were similar between groups (P = NS for all comparisons). ICU and hospital length of stays were similar between groups (P = .35 and P = .87, respectively). In Cox analysis, recipient age ≥70 years was not identified as a predictor of lower long-term survival after HT. CONCLUSIONS: HT recipients ≥70 years old had similar 1, 5, and 10-year survival rates compared with younger recipients. Both patient groups had similar intra- and postoperative blood utilization and frequencies of many postoperative complications. Older and younger patients had similar morbidity and mortality rates following HT. Carefully selected older patients (≥70 years) can safely undergo HT and should not be excluded from HT consideration based solely on age.

Leading Efforts to Increase Organ Donation Through Professionalization of Organ Procurement Organizations and Establishment of Organ and Tissue Donor Registries.

OBJECTIVE: The influence of new donor registrations through the California Organ and Tissue Donor Registry on the local OneLegacy Organ Procurement Organization (OPO) was examined during a 6-year period. METHODS: Publicly available data from Donate Life America for California were examined for the 6 calendar years of 2009-2014. Performance data from OneLegacy for the same 6 years for organ donors and number of transplants were also examined. The donor designation rate (DDR) was defined as the rate at which new individuals joined the state donor registry as a percentage of all driver licenses and ID cards issued within a calendar year. The total donor designation (TDD) was defined as the sum of the new and existing people who were registered organ donors. Donor designation share (DDS) was the total number of designated donors as a percentage of all residents of the state who were ≥18 years old. The business practices and educational efforts of the OneLegacy OPO were examined as well. RESULTS: In California, from 2009 through 2014, the DDR was 25.5%-28%. When added to the existing donor registrations, the TDD and DDS increased each year from 2009 through 2014. With the current level of growth, it is projected that California will be able to reach a DDS of 50% by 2017. For the OneLegacy OPO, designated donors from the California Organ and Tissue Donor Registry made up 15% of the total donations in 2009, and 39% of the total donations in 2014, increasing by ∼5% each year since 2009. By increasing professionalization and transparency, and widening its educational and training efforts, OneLegacy was able to take advantage of an increasing percentage of donors who were designated donors and to increase the overall number of donors and organs transplanted, becoming one of the largest OPOs in the nation. CONCLUSIONS: This can be a model for OPOs in other donor service areas, and it may set the stage for the United States to serve as an example to the global community in the practice of organ donation.

Adult Heart Transplantation Following Ventricular Assist Device Implantation: Early and Late Outcomes.

PURPOSE: The impact of prior implantation of a ventricular assist device (VAD) on short- and long-term postoperative outcomes of adult heart transplantation (HTx) was investigated. METHODS: Of the 359 adults with prior cardiac surgery who underwent HTx from December 1988 to June 2012 at our institution, 90 had prior VAD and 269 had other (non-VAD) prior cardiac surgery. RESULTS: The VAD group had a lower 60-day survival when compared with the Non-VAD group (91.1% ± 3.0% vs 96.6% ± 1.1%; P = .03). However, the VAD and Non-VAD groups had similar survivals at 1 year (87.4% ± 3.6% vs 90.5% ± 1.8%; P = .33), 2 years (83.2% ± 4.2% vs 88.1% ± 2.0%; P = .21), 5 years (75.7% ± 5.6% vs 74.6% ± 2.9%; P = .63), 10 years (38.5% ± 10.8% vs 47.6% ± 3.9%; P = .33), and 12 years (28.9% ± 11.6% vs 39.0% ± 4.0%; P = .36). The VAD group had longer pump time and more intraoperative blood use when compared with the Non-VAD group (P < .0001 for both). Postoperatively, VAD patients had higher frequencies of >48-hour ventilation and in-hospital infections (P = .0007 and .002, respectively). In addition, more VAD patients had sternal wound infections when compared with Non-VAD patients (8/90 [8.9%] vs 5/269 [1.9%]; P = .005). Both groups had similar lengths of intensive care unit (ICU) and hospital stays and no differences in the frequencies of reoperation for chest bleeding, dialysis, and postdischarge infections (P = .19, .70, .34, .67, and .21, respectively). Postoperative creatinine levels at peak and at discharge did not differ between the 2 groups (P = .51 and P = .098, respectively). In a Cox model, only preoperative creatinine ≥1.5 mg/dL (P = .006) and intraoperative pump time ≥210 minutes (P = .022) were individually considered as significant predictors of mortality within 12 years post-HTx. Adjusting for both, pre-HTx VAD implantation was not a predictor of mortality within 12 years post-HTx (hazard ratio [HR], 1.23; 95% confidence interval [CI], 0.77-1.97; P = .38). However, pre-HTx VAD implantation was a risk factor for 60-day mortality (HR, 2.86; 95% CI, 1.07-7.62; P = .036) along with preoperative creatinine level ≥2 mg/dL (P = .0006). CONCLUSIONS: HTx patients with prior VAD had lower 60-day survival, higher intraoperative blood use, and greater frequency of postoperative in-hospital infections when compared with HTx patients with prior Non-VAD cardiac surgery. VAD implantation prior to HTx did not have an additional negative impact on long-term morbidity and survival following HTx. Long-term (1-, 2-, 5-, 10-, and 12-year) survival did not differ significantly in HTx patients with prior VAD or non-VAD cardiac surgery.

Total Artificial Heart as Bridge to Heart Transplantation in Chagas Cardiomyopathy: Case Report.

Chagas disease (CD) is becoming an increasingly recognized cause of dilated cardiomyopathy outside of Latin America, where it is endemic, due to population shifts and migration. Heart transplantation (HTx) is a therapeutic option for end-stage cardiomyopathy due to CD, but may be considered a relative contraindication due to potential reactivation of the causative organism with immunosuppression therapy. The total artificial heart (TAH) can provide mechanical circulatory support in decompensated patients with severe biventricular dysfunction until the time of HTx, while avoiding immunosuppressive therapy and removing the organ most affected by the causative organism. We report herein a patient with CD and severe biventricular dysfunction, who had mechanical circulatory support with a TAH for more than 6 months, followed by successful orthotopic HTx and treatment with benznidazole for 3 months. The patient had no evidence of recurrent disease in the transplanted heart based on endomyocardial biopsy up to 1 year post-transplantation, and remains alive more than 30 months after insertion of a TAH and 24 months after HTx.

Prior sternotomy increases the mortality and morbidity of adult heart transplantation.

BACKGROUND: This study investigated the effect of prior sternotomy (PS) on the postoperative mortality and morbidity after orthotopic heart transplantation (HTx). METHODS: Of 704 adults who underwent HTx from December 1988 to June 2012 at a single institution, 345 had no PS (NPS group) and 359 had ≥ 1 PS (PS group). Survival, intraoperative use of blood products, intensive care unit (ICU) and hospital stays, frequency of reoperation for bleeding, dialysis, and >48-hour ventilation were examined. RESULTS: The NPS and PS groups had similar 60-day survival rates (97.1 ± 0.9% vs 95.3 ± 1.1%; P = .20). However, the 1-year survival was higher in the NPS group (94.7 ± 1.2% vs 89.7 ± 1.6%; hazard ratio [HR], 1.98; 95% CI, 1.12-3.49; P = .016). The PS group had longer pump time and more intraoperative blood use (P < .0001 for both). Postoperatively, the PS group had longer ICU and hospital stays, and higher frequencies of reoperation for bleeding and >48-hour ventilation (P < .05 for all comparisons). Patients with 1 PS (1PS group) had a higher 60-day survival rate than those with ≥ 2 PS (2+PS group; 96.7 ± 1.1% vs 91.1 ± 3.0%; HR, 2.70; 95% CI, 1.04-7.01; P = .033). The 2+PS group had longer pump time and higher frequency of postoperative dialysis (P < .05 for both). Patients with prior VAD had lower 60-day (91.1 ± 3.0% vs 97.1 ± 0.9%; P = .010) and 1-year (87.4 ± 3.6% vs 94.7 ± 1.2%; P = .012) survival rates than NPS group patients. Patients with prior CABG had a lower 1-year survival than NPS group patients (89.0 ± 2.3% vs 94.7 ± 1.2%; P = .018). CONCLUSION: The PS group had lower 1-year survival and higher intraoperative blood use, postoperative length of ICU and hospital stays, and frequency of reoperation for bleeding than the NPS group. Prior sternotomy increases morbidity and mortality after HTx.

Combined heart-kidney transplantation after total artificial heart insertion.

We present the first single-center report of 2 consecutive cases of combined heart and kidney transplantation after insertion of a total artificial heart (TAH). Both patients had advanced heart failure and developed dialysis-dependent renal failure after implantation of the TAH. The 2 patients underwent successful heart and kidney transplantation, with restoration of normal heart and kidney function. On the basis of this limited experience, we consider TAH a safe and feasible option for bridging carefully selected patients with heart and kidney failure to combined heart and kidney transplantation. Recent FDA approval of the Freedom driver may allow outpatient management at substantial cost savings. The TAH, by virtue of its capability of providing pulsatile flow at 6 to 10 L/min, may be the mechanical circulatory support device most likely to recover patients with marginal renal function and advanced heart failure.

Left ventricular assist device in patients with body mass index greater than 30 as bridge to weight loss and heart transplant candidacy.

INTRODUCTION: In obese patients with heart failure, weight reduction may be difficult due to physical restrictions, but may be necessary to achieve heart transplant candidacy. We report the outcomes of obese patients who underwent implantation of a left ventricular assist device (LVAD) using a pulsatile (HeartMate XVE [XVE]) or continuous flow (HeartMate II [HMII]) design and the effect on body mass index (BMI). METHODS: Of 37 patients with BMI >30 kg/m(2) who underwent LVAD implantation, 29 survived at least 30 days and were followed for weight change. In the 30-day survivors, end points of the study were continued LVAD support, heart transplant, or death. One patient underwent gastric bypass surgery and was excluded. RESULTS: In the 28 patients who met inclusion criteria, BMI was 35.6 ± 4.4 kg/m(2) at baseline, and at follow-up was 33.1 ± 5.5 kg/m(2) (mean BMI change -2.5 kg/m(2); P = .063), with a mean follow-up time of 301.6 ± 255.5 days. The XVE group showed a significant BMI reduction of 3.9 kg/m(2) (P = .016 vs baseline); however, the HMII group showed 0.1 kg/m(2) increase in BMI. BMI <30 kg/m(2) at follow-up was achieved in 6 patients (21%), 5 of 19 (26%) in XVE group, and 1 of 9 (11%) in HMII group. In the 14 patients (12 XVE, 2 HMII) or 50% who received a heart transplant, the mean decrease in BMI was 4.6 kg/m(2) (P = .003). CONCLUSIONS: LVAD placement in patients with BMI >30 kg/m(2) provided significant weight loss in the pulsatile XVE group, but not in recipients of the continuous flow HMII. In patients successfully bridged to a heart transplant after LVAD insertion, mean reduction in BMI was 4.6 kg/m(2) (P = .003). LVAD implantation provides a period of hemodynamic support for obese patients with advanced heart failure, during which time opportunity may be available for weight loss. Pulsatile devices appear to be associated with greater weight loss than nonpulsatile continuous flow devices. Additional therapies may be necessary to achieve significant weight loss in recipients of the continuous flow LVAD.

Endomyocardial biopsy technique for orthotopic heart transplantation and cardiac stem-cell harvesting.

INTRODUCTION: Orthotopic heart transplantation (OHT) is performed using the bicaval and pulmonary venous anastomoses or the standard (biatrial) anastomoses. The special considerations of endomyocardial biopsy after OHT using the bicaval technique, and after myocardial infarction for harvesting of cardiac stem cells, have not been described. METHODS: When approached via the right or left internal jugular vein, important technical considerations were ultrasound guidance for vascular access; a soft, 80-cm, 0.035-inch, J-tipped guidewire; a long (23-cm), 7-Fr sheath; and a flexible 7-Fr, 50-cm bioptome. These technical aspects were helpful to avoid disruption of the superior vena cava suture line, avoid entry into the right atrial appendage or coronary sinus, avoid right ventricular free wall perforation, and provide ready access to the right ventricular septal wall. We used the same principles and technical considerations when obtaining the cardiac stem cells after myocardial infarction in patients enrolled in the CADUCEUS trial. RESULTS: From January 2002 to December 2005, 754 biopsy procedures were performed in 179 patients after OHT with the bicaval technique, using bioptome A. There was 1 occurrence of ventricular fibrillation requiring cardioversion, and no occurrence of cardiac tamponade during the procedure. From January 2006 to September 2013, 2818 biopsy procedures were performed in 1064 patients using bioptome B. No patient developed ventricular fibrillation or cardiac tamponade during the procedure. In 2010 and 2011, 23 biopsy procedures were performed in 23 patients after acute myocardial infarction, using bioptome B. No immediate complications occurred while performing these biopsies. The late occurrence of tricuspid regurgitation was not evaluated in this study. CONCLUSIONS: Endomyocardial biopsy procedures can be safely performed after OHT with the bicaval technique and after myocardial infarction for harvesting of cardiac stem cells. Ultrasound guidance for vascular access, a long guidewire and sheath, and a flexible bioptome are important features for the safe conduct of the biopsy procedure.

Dobutamine-induced fever and isolated eosinophilic myocarditis in a 66-year-old male awaiting heart transplantation: a case report.

A 66-year-old male with non-ischemic dilated cardiomyopathy who presented for decompensated heart failure and heart transplant evaluation had to be temporarily delisted from the transplant list due to fever. No infectious source was identified and drug fever was suspected. Dobutamine was discontinued and his fever subsequently defervesced. He eventually received an orthotopic heart transplantation without complication. Explanted heart showed eosinophilic myocarditis with pathologic features consistent with a drug-induced pattern of myocarditis. Throughout the hospital course, he did not develop peripheral blood eosinophilia to suggest eosinophilic myocarditis. The importance of this report is to have a greater awareness of dobutamine-induced fever and eosinophilic myocarditis even in patients without peripheral eosinophilia. In febrile patients receiving prolonged dobutamine infusion with no other evidence of infection, consideration should be given to discontinuing dobutamine or switching to an alternative inotrope such as milrinone.

Heart transplantation for Chagas cardiomyopathy in the United States.

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Use of ventricular assist device as bridge to simultaneous heart and kidney transplantation in patients with cardiac and renal failure.

BACKGROUND: Ventricular assist device (VAD) implantation as a bridge to cardiac transplantation is an effective treatment option for end-stage heart failure. Renal dysfunction is not uncommon but is considered to be a poor prognostic factor. We present our experience with 6 patients who had combined heart and kidney transplantation (HKT) after VAD implantation for advanced cardiac and renal failure. METHODS: Of 74 patients who underwent VAD implantation as a bridge to transplant from May 2001 to September 2009, 28 patients developed renal failure, and of these, 6 (5 male, 1 female, ages 40-64 years) had HKT. All required hemodialysis because of renal failure before HKT. Immunosuppression consisted of anti-thymocyte globulin followed by triple drug therapy consisting of calcineurin inhibitors, mycophenolate, and corticosteroids. RESULTS: Of the 6 HKT patients, 5 (83%) were alive without hemodialysis at 1 and 2 years; of the 22 patients with renal failure after VAD implantation without subsequent transplant, 1- and 2-year survivals were zero. Interval from VAD implantation to HKT ranged from 36 to 366 days (133 ± 127 days). At 6 months after HKT (100% alive), left ventricular ejection fraction was 60.2 ± 5.8% and serum creatinine 1.1 ± 0.2 mg/dL. Three HKT patients required temporary hemodialysis after surgery. Endomyocardial biopsy showed absence of ISHLT grade 2R-3A or greater cellular rejection, and none showed evidence of definite antibody-mediated rejection. CONCLUSIONS: Based on our initial experience, simultaneous HKT is a safe treatment option with excellent outcomes for patients with advanced heart failure and persistent renal dysfunction after VAD implantation.

Heart transplantation for end-stage heart failure due to cardiac sarcoidosis.

BACKGROUND: Cardiac sarcoidosis with end-stage heart failure has a poor prognosis without transplantation. The rates of sarcoid recurrence and rejection are not well established after heart transplantation. METHODS: A total of 19 heart transplant recipients with sarcoid of the explanted heart were compared with a contemporaneous control group of 1,050 heart transplant recipients without cardiac sarcoidosis. Assessed outcomes included 1st-year freedom from any treated rejection, 5-year actuarial survival, 5-year freedom from cardiac allograft vasculopathy (CAV), 5-year freedom from nonfatal major adverse cardiac events (NF-MACE), and recurrence of sarcoid in the allograft or other organs. Patients with sarcoidosis were maintained on low-dose corticosteroids after transplantation. RESULTS: There were no significant differences between the sarcoid and control groups in 1st-year freedom from any treated rejection (79% and 90%), 5-year posttransplantation survival (79% and 83%), 5-year freedom from CAV (68% and 78%), and 5-year freedom from NF-MACE (90% and 88%). Causes of death (n = 5) in the sarcoid group were coccidioidomycosis, pneumonia, rejection, hemorrhage, and CAV. No patient had recurrence of sarcoidosis in the cardiac allograft. Three of 19 patients (16%) experienced recurrence of extracardiac sarcoid, with no mortality. CONCLUSIONS: Patients with cardiac sarcoidosis undergoing heart transplantation have acceptable long-term outcomes without evidence of recurrence of sarcoidosis in the allograft when maintained on low-dose corticosteroids. Progression of extracardiac sarcoid was uncommon, possibly related to immunosuppression. In patients with cardiac sarcoidosis, heart transplantation is a viable treatment modality.

Antithymocyte globulin induction therapy adjusted for immunologic risk after heart transplantation.

INTRODUCTION: The efficacy of antithymocyte globulin (ATG) induction in the therapy of immunologically low- and high-risk patients after heart transplantation is not known. METHODS: All patients who received ATG induction from January 2000 through January 2010 were divided into two groups based on the risk of rejection. A higher-risk group (age younger than 60 years, multiparous females, African Americans, panel-reactive antibody >10%, or positive cross-match) received ATG (1.5 mg/kg) for 7 days (ATG7), and the remaining lower-risk group received ATG for 5 days (ATG5), all followed by calcineurin inhibitor, mycophenolate, and prednisone. Endomyocardial biopsies were performed based a standard protocol for up to 3 years after heart transplantation, and for suspected rejection. RESULTS: Of 253 heart transplant recipients, 87 received ATG5 and 166 ATG7. Absolute lymphocyte count <200 per microliter was achieved within 10 days in 88% of ATG5 and 86% of ATG7. Baseline creatinine was 1.3 ± 0.8 pre-transplantation, 1.8 ± 0.9 post-transplantation, and 1.0 ± 0.4 mg/dL at discharge (mean ± standard deviation [SD]; P < .001, compared with pre-transplantation). Of 3667 biopsies, 33 (0.90%) had ≥3A/2R cellular rejection (CR). Of 3599 biopsies, 16 (0.44%) had definite antibody-mediated rejection (AMR). At 5 years, freedom from ≥3A/2R CR (94% ± 2.8% vs 83% ± 7.7%; P = .31) and freedom from AMR (95% ± 2.4% vs 90% ± 6.4%; P = .98) were similar between ATG5 and ATG7, respectively. Survival for ATG5 and ATG7 was comparable at one year (94% ± 2.5% vs 93% ± 2.0%), and at 8 years (61% ± 6.9% and 61% ± 4.7%; P = .88). At 5 years, ATG5 and ATG7 were similar in freedom from cytomegalovirus (CMV) infection (92.3% vs 94.3%; P = not significant [NS]), freedom from pneumonia (83.8% vs 82.1%; P = NS), and in rate of malignancy (excluding skin cancer; 8.0% vs 6.0%; P = NS). CONCLUSIONS: ATG induction therapy (prospectively dose-adjusted for immunologic risk) in low- and high-risk patients results in excellent and equivalent short- and long-term survival rates, with a low incidence of CR and AMR. The use of ATG does not increase rates of CMV infection with appropriate prophylaxis. ATG may benefit renal function by delaying calcineurin inhibitor exposure, and may have a role in the prevention of AMR.

Bariatric surgery in severe obesity and end-stage heart failure with mechanical circulatory support as a bridge to successful heart transplantation: a case report.

We present the first report of the concurrent use of mechanical circulatory support and bariatric surgery in a morbidly obese patient as a bridge to successful heart transplantation. The concurrent use of mechanical circulatory support and bariatric surgery allowed the patient to lose weight and subsequently to qualify for placement on the heart transplant waiting list. This strategy supports consideration of patients previously deemed unsuitable for heart transplantation owing to morbid obesity. Careful patient selection and strict monitoring of the immunosuppressive regimens are important considerations for a favorable outcome.

Aortic valve replacement or heart transplantation in patients with aortic stenosis and severe left ventricular dysfunction.

INTRODUCTION: The decision to perform aortic valve replacement (AVR) or heart transplantation (HTx) for aortic stenosis (AS) with severe left ventricular dysfunction is difficult and may be affected by prior myocardial infarction (MI) and coronary artery disease (CAD). METHODS: Patients who underwent AVR from 1988 to 2001 with left ventricular ejection fraction (LVEF) <30% and severe AS (aortic valve area [AVA] < 1.0 cm(2); n = 51) were assessed for operative mortality, late survival, and predictors of outcome, and were compared with HTx. Subsequently, 131 patients with LVEF ≤ 35% who underwent AVR for critical AS (AVA < 0.8 cm(2)) were evaluated. RESULTS: In the first 51 patients, 3-year survival was 100% ± 0% with no CAD, and 45% ± 10% with CAD (P < .05); 3-year survival was 88% ± 12% with no bypass, 73% ± 12% with one to two grafts, and 18% ± 11% with three grafts (P < .01). Survival with HTx was 78% at 3 years. In the subsequent analysis of 131 patients, 90-day survivors were followed for a mean 4.6 ± 3.5 years. Advanced age (P = .001) was the only predictor of long-term mortality. LVEF improved from 28.5% ± 5.2% before AVR to 45.4% ± 13.2% at 1-month postoperatively (P < .0001). New York Heart Association (NYHA) class III/IV decreased from 94.2% pre-AVR to 12.8% at 1 year (P < .0001). Predictors of LVEF recovery were no previous MI (P = .007) and higher AS gradient (P = .03). CONCLUSIONS: In severe AS and LVEF <30% with no concomitant CAD or with CAD requiring one to two bypass grafts, AVR has a survival equal to or exceeding that of HTx. In patients with CAD requiring more than two bypass grafts, survival is significantly reduced, and HTx can be considered.

Concomitant dual intravascular and subcutaneous microsurgical implantation of xenograft tissue in a rodent model for evaluation of structural degeneration.

INTRODUCTION: An economical animal model to study xenograft tissue degeneration and calcification and the durability of biological vascular patch material and bioprosthetic valve leaflets is desirable. OBJECTIVE: A cost-effective model to analyze xenograft degeneration, calcification, immunologic reaction, and anticalcification treatment was developed. Furthermore, a technique for implant into the vascular lumen of the abdominal aorta in rats is presented. METHODS: Twelve Lewis rats were used as recipients. The microsurgical procedure was performed using a high-definition optical system. Anesthesia was induced and maintained with isoflurane inhalation. The suprarenal and infrarenal portion of the abdominal aorta was isolated, the abdominal aorta was cross-clamped, and a 4-mm square portion of the abdominal aorta was removed. Subsequently, a complementary-sized piece of porcine or bovine glutaraldehyde-fixed bioprosthetic valve leaflet tissue was sutured as a patch in the abdominal aorta. RESULTS: The mean operating time was 45 ± 10 minutes and the mean ischemic time was 25 ± 5 minutes. Early and 3-month survivals were 100%. One rat had intraoperative bleeding. No paralysis or thrombosis was observed. CONCLUSION: Feasibility and reproducibility of removing a portion of the abdominal aorta and replacing it with a patch of xenograft tissue was demonstrated in a rodent model with 100% survival at 3 months. Concomitant dual intravascular and subcutaneous microsurgical implantation of xenograft tissue in a small-animal (rat) model is a cost-effective approach for investigation of xenograft tissue degeneration.

High definition optical system for microsurgical heterotopic heart transplantation in rats.

BACKGROUND: Clinical and experimental cardiovascular surgery as well as other surgical disciplines may require visualization and manipulation of small anatomic structures. A high-definition optical system was developed for magnification and illumination as an alternative to surgical loupes or a traditional operating microscope. MATERIALS AND METHODS: A video telescopic optical imaging system that provided a high-definition and magnification of the surgical field was used for visualization of small anatomic structures and as an aid to the performance of small vessel anastomoses in a series of 10 heterotopic heart transplants (HHTx) in rats. RESULTS: The video telescopic optical system was easy to manipulate and comfortable to use, and provided high-definition images for magnification of anatomic structures while performing microvascular cardiac surgery in a small animal model of HHTx in rats. Fatigue and neck problems for the surgeon were reduced. CONCLUSIONS: The video telescopic imaging system provided high definition and magnification of the surgical field, and was used for visualization of small anatomic structures and as an aid to the performance of small vessel anastomoses. The system is an alternative to surgical loupes or a traditional operating microscope, and was used for the first time in microvascular cardiac surgery in a rat HHTx model.

Heart transplantation in patients aged 70 years and older: a two-decade experience.

OBJECTIVE: Advanced age has been viewed as a contraindication to orthotopic heart transplantation (OHT). We analyzed the outcome of OHT in patients who were aged 70 years or older and compared the results with those in younger patients during a two-decade period. METHODS: A total of 519 patients underwent first-time single-organ OHT at our institution from 1988 to 2009. Patients were divided into three groups by age: ≥70-years old (group 1, n=37), 60 to 69-years old (group 2, n=206), and ≤60-years old (group 3, n=276). Primary endpoints were 30-days, and 1-, 5-, and 10-years survival. Secondary outcomes included re-operation for bleeding, postoperative need for dialysis, and length of postoperative intubation. RESULTS: There was no significant difference in survival between the greater than or equal to 70-year-old group and the two younger age groups for the first 10 years after OHT. Survival rates at 30 days, and 1-, 5-, and 10-years, and median survival in group 1 recipients were 100%, 94.6%, 83.2%, 51.7%, and 10.9 years (CI 7.1-11.0), respectively; in group 2 those numbers were 97.6%, 92.7%, 73.8%, 47.7%, and 9.1 years (CI 6.7-10.9), respectively; and in group 3 those numbers were 96.4%, 92.0%, 74.7%, 57.1%, and 12.2 years (CI 10.7-15.4; P=NS), respectively. There was no significant difference in secondary outcomes of re-operation for bleeding, postoperative need for dialysis, and prolonged intubation among the three age groups. CONCLUSIONS: Patients who are aged 70 years and older can undergo heart transplantation with similar morbidity and mortality when compared with younger recipients. Advanced heart failure patients who are aged 70 years and older should not be excluded from transplant consideration based solely on an age criterion. Stringent patient selection, however, is necessary.