Venovenous Extracorporeal Membrane Oxygenation for Acute Respiratory Failure in a Liver Transplant Patient: A Case Report.

Intraoperative extracorporeal membrane oxygenation (ECMO) support, both venoarterial and venovenous (VV), have been used sparingly and with limited success in the setting of liver transplantation. Here, we report the successful use of VV-ECMO in the resuscitation and pulmonary bridging support after severe systemic inflammatory response in a combined liver and kidney transplant recipient who suffered primary nonfunction of both allografts. Where conventional ventilator maneuvers may prove ineffective, the implementation of VV-ECMO should be considered as a therapeutic option in limited, short-lived acute pulmonary injury.

Comparative analysis of von Willebrand factor profiles after implantation of left ventricular assist device and total artificial heart.

Essentials Bleeding is a major source of morbidity during mechanical circulatory support. von Willebrand factor (VWF) multimer loss may contribute to bleeding. Different patterns of VWF multimer loss were seen with the two device types. This is the first report of total artificial heart associated VWF multimer loss. SUMMARY: Background Bleeding remains a challenge during mechanical circulatory support and underlying mechanisms are incompletely understood. Functional von Willebrand factor (VWF) impairment because of loss of high-molecular-weight multimers (MWMs) produces acquired von Willebrand disease (VWD) after left ventricular assist device (LVAD). Little is known about VWF multimers with total artificial hearts (TAHs). Here, VWF profiles with LVADs and TAHs are compared using a VWD panel. Methods VWD evaluations for patients with LVAD or TAH (2013-14) were retrospectively analyzed and included: VWF activity (ristocetin cofactor, VWF:RCo), VWF antigen (VWF:Ag), ratio of VWF:RCo to VWF:Ag, and quantitative VWF multimeric analysis. Results Twelve patients with LVADs and 12 with TAHs underwent VWD evaluation. All had either normal (47.8%) or elevated (52.2%) VWF:RCo, normal (26.1%) or elevated (73.9%) VWF:Ag and 50.0% were disproportional (ratio ≤ 0.7). Multimeric analysis showed abnormal patterns in all patients with LVADs: seven with high MWM loss; five with highest MWM loss. With TAH, 10/12 patients had abnormal patterns: all with highest MWM loss. High MWM loss correlated with presence of LVAD and highest MWM loss with TAH. Increased low MWMs were detected in 22/24. Conclusion Using VWF multimeric analysis, abnormalities after LVAD or TAH were detected that would be missed with measurements of VWF level alone: loss of high MWM predominantly in LVAD, loss of highest MWM in TAH, and elevated levels of low MWM in both. This is the first study to describe TAH-associated highest MWM loss, which may contribute to bleeding.

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.

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.

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.

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.

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.

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.

mTOR inhibition induces endothelial progenitor cell death.

Immunosuppressants are necessary to prevent graft rejection after solid organ transplantation. However, they are also known to have significant side effects, including endothelial toxicity. Endothelial progenitor cells originate in the bone marrow and are recognized by their angiogenic and endothelial reparative properties. The effects of the immunosuppressants cyclosporine A (CyA), tacrolimus and rapamycin were analyzed on endothelial progenitor-like cells. Rapamycin induced rapid cell death, even at concentrations much lower than those used clinically, in peripheral blood mononuclear cells (PBMC) cultured to favor outgrowth of endothelial progenitors. Cyclosporine A and tacrolimus had no significant effects at clinical concentrations. The effect of rapamycin was specific to endothelial progenitor cells, in particular to the early stages of differentiation, as a lesser effect was observed in late outgrowth endothelial progenitors, mature aortic endothelial cells, and macrophages derived from the same PBMCs. The mechanism of cell death appeared to be apoptosis; however, its induction was probably multifactorial and did not depend on caspase or cathepsin activation. In conclusion, rapamycin induces endothelial progenitor cell death, possibly because it blocks survival signals given by growth factors critically required by these cells.