Aaron H. Healy

Improving outcomes with long-term “destination” therapy using left ventricular assist devices

OBJECTIVE Destination therapy experience using long-term left ventricular assist devices was analyzed relative to the benchmark Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial to evaluate the potential for improving outcomes with this groundbreaking therapy for advanced heart failure. METHODS The largest single-center experience with destination therapy in the United States (Utah Artificial Heart Program, LDS Hospital, Salt Lake City, UT) was retrospectively analyzed. All destination therapy recipients (n = 23) presented with chronic, advanced heart failure, meeting indications for destination therapy adopted from the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. All received HeartMate left ventricular assist devices (Thoratec Corp, Pleasanton, Calif), with 87% receiving an improved XVE model. Advanced practice guidelines were implemented using a multidisciplinary approach. Survivals (Kaplan-Meier, log-rank analyses) and adverse events (Poisson regression) were compared with those of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (n = 68). RESULTS Survival in the destination therapy group was significantly increased (P = .007), with an overall reduction in mortality of 66%. The 2-year survival was 77% for destination therapy compared with 29% for the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device group (P < .0001). The 1-year survival was 77% for destination therapy compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 52% (P = .036). Adverse events decreased by 38% (3.90 per patient-year in the destination therapy group compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure left ventricular assist device rate of 6.32). Factors related to severity of illness met Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure-like criteria for both groups. CONCLUSIONS This analysis provides evidence that long-term destination therapy can be improved well beyond the pioneering experience of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. With continued evolution of devices, management, and patient selection, outcomes approaching those of heart transplantation may be possible.

Impact of Ventricular Assist Device Complications on Posttransplant Survival: An Analysis of the United Network of Organ Sharing Database

BACKGROUND Although current left ventricular assist device (LVAD) technology has proven more durable than first-generation devices, all mechanical devices are prone to complications that can elevate patient acuity before transplantation. LVAD patients with complications intuitively carry a higher risk profile than other status 1A LVAD patients who are generally stable and use their 30 days of clinically stable status 1A time. We sought to determine if the presence or absence of complications in status 1A LVAD patients at the time of transplant influenced survival after transplant. METHODS The United Network of Organ Sharing database was retrospectively analyzed for 15,253 patients who were listed status 1A from 1998 to 2008. Survival after transplant survival was compared between patients who were and were not listed for LVAD-related complications. Standard statistical analysis was applied. RESULTS No survival difference was identified at 1 and 10 years after transplant in patients who had device complications compared with those without complications. Of the five complication entries (thromboembolism, infection, malfunction, malignant arrhythmia, and other), only device infection increased mortality risk compared with noncomplicated patients (39% at 1 year, 30% at 10 years, p < 0.01). CONCLUSIONS Long-term outcomes are generally not affected by the status 1A listing criteria for patients bridged to transplant with LVADs. However, the subset of patients with device infection had worse 1-year and 10-year posttransplant survival. Bridge to transplant patients, despite serious device-related complications, still have excellent transplant outcomes.

Bridge to Removal: A Paradigm Shift for Left Ventricular Assist Device Therapy

Ventricular assist devices have become standard therapy for patients with advanced heart failure either as a bridge to transplantation or destination therapy. Despite the functional and biologic evidence of reverse cardiac remodeling, few patients actually proceed to myocardial recovery, and even fewer to the point of having their device explanted. An enhanced understanding of the biology and care of the mechanically supported patient has redirected focus on the possibility of using ventricular assist devices as a bridge to myocardial recovery and removal. Herein, we review the current issues and approaches to transforming myocardial recovery to a practical reality.

Predictors of 30-day post-transplant mortality in patients bridged to transplantation with continuous-flow left ventricular assist devices - An analysis of the International Society for Heart and Lung Transplantation Transplant Registry

BACKGROUND Continuous-flow (CF) left ventricular assist devices (LVADs) are standard of care for bridging patients to cardiac transplantation. However, existing data about preoperative factors influencing early post-transplant survival in these patients are limited. We sought to determine risk factors for mortality using a large international database. METHODS All patients in the International Society for Heart and Lung Transplantation Transplant Registry who were bridged to transplantation with CF LVADs between June 2008 and June 2012 were included. Risk factors for mortality within 30 days of transplant were identified. Statistical analysis included multivariable analysis and Kaplan-Meier survival analysis. RESULTS During the study period, 2,152 patients with CF LVADs underwent heart transplantation. Post-transplant survival was 95.5% at 30 days. Risk factors for mortality during this window included ventilator support at transplant (hazard ratio [HR] = 5.00, 95% confidence interval [CI] = 1.51-16.58), female recipient/male donor (compared with all other combinations, HR = 3.29, 95% CI = 1.90-5.72), history of hemodialysis (HR = 2.51, 95% CI = 1.14-5.51), and history of coronary bypass grafting (HR = 1.89, 95% CI = 1.19-3.00). Increasing recipient age (p = 0.002), body mass index (p = 0.002), creatinine (p = 0.004), and total bilirubin (p < 0.001) also were associated with an increase in mortality. CONCLUSIONS In patients supported with CF LVADs, risk factors for early mortality can be identified before transplant, including ventilator support, female recipient/male donor, increasing recipient age, and body mass index. Despite the inherent complexities of a reoperative surgery, patients bridged to transplant with CF LVADs have excellent peri-operative survival.

Allograft Rejection in Patients Supported With Continuous-Flow Left Ventricular Assist Devices

BACKGROUND Both pulsatile-flow and continuous-flow left ventricular assist devices (LVADs) successfully provide patients a bridge to transplantation. Some data suggest that continuous-flow pumps increase the risk of allograft rejection, contributing to posttransplantation morbidity and mortality. We sought to analyze the relationship between LVAD flow characteristics and subsequent allograft rejection in bridge to transplant (BTT) patients. METHODS Patients with LVADs from the UTAH Transplant Affiliated Hospitals were retrospectively analyzed. Rejection was determined pathologically according to the International Society for Heart and Lung Transplantation revised cardiac allograft rejection scale. Multimodal statistical analyses were applied. RESULTS Of 1,076 patients who underwent transplantation over a 26-year period, 151 had LVADs. Of these, 111 (77 pulsatile flow, 34 continuous flow) patients had pathologic data available. There was no difference in overall rejection (grades 1R to 3R) between the pulsatile-flow LVAD and continuous-flow LVAD groups (2.00 ± 1.43 versus 1.50 ± 1.16 episodes/year; p = 0.076.) Patients with pulsatile-flow LVADs had more clinically relevant (grades 2R to 3R) rejection than did patients with continuous-flow LVADs (0.49 ± 0.72 versus 0.12 ± 0.33 episodes/year; p < 0.001). There was no survival difference at 1 year (p = 0.920) or 4 years (p = 0.721) after transplantation. CONCLUSIONS Patients with continuous-flow LVADs have similar overall rejection rates and a reduced rate of clinically relevant rejection compared with patients with pulsatile-flow LVADs during the first year after transplantation. Although there is theoretical concern that nonphysiologic, nonpulsatile flow could alter the neurohormonal profile of patients in heart failure, we are encouraged that the type of LVAD circulation does not influence posttransplantation allograft survival.

Antibiotic-Impregnated Beads for the Treatment of Aortic Graft Infection

Infection of a prosthetic graft after replacement of the ascending aorta is an uncommon but life-threatening complication of surgery. We report the use of antibiotic-impregnated calcium sulfate beads in a patient with ascending aortic graft infection to provide localized, high-dose therapy to the infected region. Perigraft placement of antibiotic beads provides an alternative method for the treatment of aortic graft infection.

Patient-Controlled Conditioning for Left Ventricular Assist Device–Induced Myocardial Recovery

Although medical protocols exist to promote reverse remodeling in left ventricular assist device-supported patients, there are scant data about device management in these patients. We report the use of a Jarvik 2000 left ventricular assist device (Jarvik Heart Inc, New York, NY) to facilitate myocardial recovery leading to device explantation using a sequential, patient-controlled approach. Sequential conditioning of the left ventricular assist device-supported heart is a promising strategy for bridging patients to recovery and pump removal.