M. De Robertis

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.

Survival and Allograft Rejection Rates after Combined Heart and Kidney Transplantation in Comparison with Heart Transplantation Alone

BACKGROUND The role of solid multiorgan transplantation remains to be determined. We compared our experience with combined heart-kidney transplantation (HKT) and heart transplant alone (HT), and assessed patient survival rates and freedom from allograft rejection in these two patient groups. METHODS We reviewed the clinical outcomes of patients undergoing HKT (n=30) or HT (n=440) between June 1992 and March 2009. Baseline patient characteristics, perioperative factors, incidence of rejection, and survival were examined. RESULTS There were no significant differences between the two groups for age, gender, etiology of heart disease, functional class, preoperative left ventricular ejection fraction, end-diastolic diameter, cardiac output, or transplant waitlist status. Patients with HKT had a higher serum creatinine level (P<.001) and a greater incidence of hypertension (P=.04). No differences were found in cardiac allograft ischemic times, including cardiopulmonary bypass or cross-clamp times. Kidney allograft ischemic time was 14.6±9 hours (mean±SD; range, 4 hours to 49 hours). Kaplan-Meier survival estimates were similar for the HKT and HT groups at 30 days (93%±4.6% versus 98%±0.7%), 1 year (87%±6.2% versus 93%±1.2%), 5 years (68%±9.0% versus 76%±2.1%), and 10 years (51%±11% versus 53%±3.0%; P=.54 for all comparisons). Follow-up serum creatinine levels were similar after HKT and HT at 30 days (1.6±1.8 mg/dL versus 1.1±0.4 mg/dL), 1 year (1.4±0.6 mg/dL versus 1.5±0.6 mg/dL), and 5 years (1.8±1.8 mg/dL versus 1.8±1.2 mg/dL; P>.05 for all comparisons). CONCLUSIONS HKT offers excellent survival and similar renal function when compared with HT alone. Patients with end-stage cardiac and renal failure can be considered for HKT.

Combined Heart and Liver Transplantation: The Cedars-Sinai Experience

PURPOSE Combined heart-liver transplantation is an increasingly accepted treatment for select patients with heart and liver disease. Despite growing optimism, heart-liver transplantation remains an infrequent operation. We report our institutional experience with heart-liver transplantation. METHODS All combined heart-liver transplantations at Cedars-Sinai Medical Center from 1998-2014 were analyzed. Primary outcomes were patient and graft survival and secondary outcomes included rejection, infection, reoperation, length of stay, and readmission. RESULTS There were 7 heart-liver transplants: 6 simultaneous (single donor) and 1 staged (2 donors). Median follow-up was 22.1 (IQR 13.2-48.4) months. Mean recipient age was 50.8 ± 19.5 years. Heart failure etiologies included familial amyloidosis, congenital heart disease, hypertrophic cardiomyopathy, systemic lupus erythematosus, and dilated cardiomyopathy. Preoperative left ventricular ejection fraction averaged 32.3 ± 12.9%. Five (71.4%) patients required preoperative inotropic support; 1 required mechanical circulatory support. The most common indications for liver transplant were amyloidosis and cardiac cirrhosis. Median Model for End-stage Liver Disease score was 10.0 (9.3-13.8). Six-month and 1-year actuarial survivals were 100% and 83.3%, with mean survival exceeding 4 years. No patient experienced cardiac allograft rejection, 1 experienced transient liver allograft rejection, and 1 developed progressive liver dysfunction resulting in death. Five developed postoperative infections and 3 (42.9%) required reoperation. Median ICU and hospital stays were 7.0 (7.0-11.5) and 17.0 (13.8-40.5) days. There were 4 (57.1%) readmissions. CONCLUSIONS For carefully selected patients with coexisting heart and liver disease, combined heart and liver transplantation offers acceptable patient and graft survival.

Heart Transplantation With and Without Prior Sternotomy: Analysis of the United Network for Organ Sharing Database

INTRODUCTION Patients with history of prior sternotomy may have poorer outcomes after heart transplantation. Quantitation of risk from prior sternotomy has not been well established. The United Network for Organ Sharing (UNOS) database was analyzed to assess early and late survival and predictors of outcome in adult heart transplant recipients with and without prior sternotomy. METHODS Of 11,266 adults with first heart-only transplantation from 1997 to 2011, recipients were divided into 2 groups: those without prior sternotomy (first sternotomy group; n = 6006 or 53.3%) and those with at least 1 prior sternotomy (redo sternotomy group; n = 5260 or 46.7%). A multivariable Cox model was used to identify predictors of mortality. RESULTS Survival was lower in the redo group at 60 days (92.6% vs 95.9%; hazard ratio [HR] 1.83, 95% confidence interval [CI]: 1.56-2.15; P < .001). Conditional 5-year survival in 60-day survivors was similar in the 2 groups (HR = 1.01, 95% CI 0.90-1.12, P = .90). During the first 60 days post-transplant, the redo group had more cardiac reoperations (12.3% vs 8.8%, P = .0008), a higher frequency of dialysis (8.9% vs 5.2%, P < .0001), a greater percentage of drug-treated infections (23.2% vs 19%, P = .003), and a higher percentage of strokes (2.5% vs 1.4%, P = .0001). A multivariable Cox proportional hazards model identified prior sternotomy as a significant independent predictor of mortality, in addition to age, female gender, congenital cardiomyopathy, need for ventilation, mechanical circulatory support, dialysis prior to transplant, pretransplant serum bilirubin (≥ 3 mg/dL), and preoperative serum creatinine (≥ 2 mg/dL). CONCLUSIONS Prior sternotomy is associated with an excess 3.3% mortality and higher morbidity within the first 60 days after heart transplantation, as measured by frequency of dialysis, drug-treated infections, and strokes. Conditional 5-year survival after 60 days is unaffected by prior sternotomy. These findings should be taken into account for risk assessment of patients undergoing heart transplantation.

Heterotopic Heart Transplantation in Rats: Improved Anesthetic and Surgical Technique

OBJECTIVE An updated anesthetic and surgical technique in a rat model of heterotopic heart transplantation is described. MATERIALS AND METHODS A microsurgical technique via a suprarenal approach was performed, and is described in stepwise fashion, and several technical improvements are compared with previous descriptions. Lewis rats were used as donors and recipients (syngeneic model). RESULTS Factors that affected early surgical outcome included type of anesthetic used; surgeon skill, experience in handling blood vessels, and knowledge of small-animal anatomy; gentle manipulation during the operation; and duration of surgery (<1 hour). Use of isoflurane inhalation anesthesia (10 rats) vs intraperitoneal injection of ketamine, 75 mg/kg, and dexmedetomidine, 0.25 mg/kg (20 rats), was associated with improved early survival (90%) and no occurrence of paralysis, paraparesis, bleeding, or intestinal ischemia. Long-term survival (>11 months) with a functioning graft was achieved in all 9 surviving animals. CONCLUSIONS Survival was substantially improved with administration of isoflurane anesthesia; surgeon microvascular surgical skills and knowledge of small-animal anatomy, and duration of surgery less than 1 hour. These factors collectively contributed to successful early outcomes after heterotopic heart transplantation in rats, with 90% freedom from morbidity and mortality, and resulted in long-term survival (>11 months) with a functioning graft in a syngeneic model. This heterotopic model in rats is suitable for short- and long-term studies of heart transplantation.

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.

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.

Prophylaxis of Cytomegalovirus Disease in Mismatched Patients after Heart Transplantation Using Combined Antiviral and Immunoglobulin Therapy

BACKGROUND Cytomegalovirus (CMV) is a common cause of infection and morbidity after heart transplantation. Seronegative recipients (R-) of seropositive donor hearts (D+) are at high risk for CMV disease. We compared three different CMV prophylaxis regimens using combined antiviral and immunoglobulin therapy. METHODS In 99 patients who survived more than 30 days after heart transplant, all received induction with antilymphocytic therapy and triple-drug therapy. In group A, D+R- patients received one dose of intravenous immunoglobulin (IVIG) followed by one dose of CMV-specific immunoglobulin (CMV-IVIG), and intravenous ganciclovir (GCV) for 4 weeks followed by 11 months of oral acyclovir (ACV). In group B, D+R- patients received one dose IVIG followed by five doses of CMV-IVIG and intravenous GCV for 14 weeks followed by 9 months of oral ACV. In group C, D+R- patients were treated with the same regimen as for group B, except oral ACV was replaced with oral GCV. RESULTS The actuarial freedom from CMV disease for D+R- patients at 1 month, 1 year, and 2 years after transplantation in group A was 100%, 25% ± 15%, and 25% ± 15%, respectively; group B was 100%, 67% ± 27%, and 67% ± 27%; group C was 100%, 83% ± 15%, and 83% ± 15% (P < .01, groups B and C vs group A). By comparison, the actuarial freedom from CMV disease for seropositive recipients (D-R+ or D+R+) at 1 month, 1 year, and 2 years in group A was 100%, 87% ± 7%, and 82% ± 8%, respectively; group B was 100%, 88% ± 8%, and 75% ± 11%; group C was 100%, 72% ± 9%, and 72% ± 9% (P = NS among groups). Rejection rates did not differ among the three groups. CONCLUSIONS A longer course of intravenous GCV with multiple doses of CMV-IVIG was a more effective prophylaxis regimen against CMV disease for the high-risk group of seronegative recipients of seropositive donor hearts.

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.

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.