Laura J. Blue

Left Ventricular Assist Device Destination Therapy Versus Extended Criteria Cardiac Transplant

BACKGROUND End-stage heart failure is a growing problem associated with a high mortality using conventional medical care. Although cardiac transplantation is an excellent treatment option, it is a limited resource and most patients are ineligible for cardiac transplantation using standard listing criteria. Increasingly, newer surgical options for these patients include the usage of marginal donor organs in an extended criteria-alternate list heart transplant program (EC-AL), or left ventricular assist devices as destination therapy (DT-LVAD). The purpose of this study was to compare baseline characteristics and outcomes after EC-AL versus DT-LVAD. METHODS From March 2000 to August 2008, 153 consecutive patients who had been turned down for standard heart transplantation underwent either EC-AL or DT-LVAD. The most common reasons for standard heart transplant ineligibility for both groups were advanced age, diabetes mellitus with end-organ dysfunction, and significant renal insufficiency. Patients in the alternate list program received a donor organ that had been turned down by all other centers for standard list recipients. The most common reasons for donor heart refusal were decreased left ventricular function, left ventricle hypertrophy, or coronary artery disease. Outcomes for both groups were retrospectively reviewed after Institutional Review Board permission was obtained. Comparisons were also made between patients that had been matched by propensity score analysis. RESULTS In all, 93 patients underwent EC-AL, and 60 underwent DT-LVAD. Baseline preoperative characteristics of both groups were similar except that 87% of DT-LVAD patients (52 of 60) required preoperative mechanical or inotropic support whereas only 51% of EC-AL patients (47 of 93) required support (p<0.0001). Thirty-day operative mortality and 1-year survival were 2.5% and 82.2% for EC-AL and 6.7% and 77.5% DT-LVAD, respectively (p=0.2411 and p=0.5036). Overall survival at 3 years was better for EC-AL versus DT-LVAD. The DT-LVAD patients had improved survival compared with the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial DT-LVAD cohort, a historical control. These findings were corroborated in the analysis of propensity-matched patients. CONCLUSIONS Preoperatively, the DT-LVAD cohort was more unstable, with greater need for inotropes or mechanical support. Despite this, perioperative and 1-year mortality was similar for the two groups. Three-year survival was better for EC-AL. The DT-LVAD patient survival was better than that of the REMATCH DT-LVAD cohort.

Impact of Tricuspid Valve Regurgitation in Patients Treated With Implantable Left Ventricular Assist Devices

BACKGROUND The progression of tricuspid valve regurgitation (TR) and the impact of preoperative TR on postoperative outcomes in patients having left ventricular assist device (LVAD) implantation has not been studied. METHODS One hundred seventy-six consecutive implantable LVAD procedures were retrospectively reviewed. A total of 137 patients comprised the final study group with complete preimplant characteristics, before and after echocardiogram assessment of TR, and outcomes data. Patients were divided into two groups: insignificant TR (iTR) consisting of those with preimplant TR grades of none, trace, and mild; and significant TR (sTR) consisting of those with moderate and severe TR grades. RESULTS Relative to patients with iTR, patients with sTR were younger (53.6±12.8 versus 58.4±10.0 years, p=0.02) and more commonly had nonischemic cardiomyopathies (69% versus 38%, p<0.001). The preimplant incidence of iTR and sTR was 51% and 49%. Immediately after the LVAD implant procedure, TR did not significantly change. At late follow-up (156±272 days), 32% had moderate or severe TR. Also, 41% of the original sTR group persisted with moderate or severe TR. Relative to patients with iTR, patients with sTR required longer postimplant intravenous inotropic support (8.5 versus 5.0 days, p=0.02), more commonly required a temporary right ventricular assist device, and had a longer postimplant length of hospital stay (27.0 versus 20.0 days, p=0.03). There was also a trend toward decreased survival for sTR versus iTR (log rank=0.05). CONCLUSIONS Tricuspid regurgitation is not reduced immediately after LVAD implantation. Significant TR is associated with longer postimplant inotropic support and length of hospital stay.

Clinical Impact of Concomitant Tricuspid Valve Procedures During Left Ventricular Assist Device Implantation

BACKGROUND Almost 50% of patients referred for implantable left ventricular assist device (LVAD) have significant tricuspid regurgitation (TR). Preoperative TR is associated with negative outcomes but the clinical benefit of concomitant tricuspid valve procedures has not been extensively studied. METHODS One hundred fifteen patients, undergoing implantable LVADs, were identified as having significant TR by echocardiography prior to their surgical procedure. Patients underwent either LVAD alone (n = 81) versus LVAD plus concomitant tricuspid procedures (n = 34) (29 annuloplasty ring repairs and 5 bioprosthetic replacements.) Preoperative characteristics and hemodynamics, as well as TR severity and clinical outcomes were retrospectively determined from chart and database review and compared for the two groups. RESULTS Preoperative characteristics and hemodynamics were similar for the two groups. Postoperative TR was markedly reduced for the group undergoing concomitant procedures versus LVAD alone. A temporary right ventricular assist device was required for only one of the 34 cases in which concomitant tricuspid procedures were performed; for patients undergoing LVAD alone, 8 of 81 required right ventricular assist devices. Mean duration of postoperative inotrope utilization was increased for the LVAD alone group versus the group with concomitant tricuspid procedures (10.0 vs 8.0 days, respectively, p = 0.04). The incidence of postoperative renal dysfunction was increased for the LVAD alone group (39%) versus concomitant procedures (21%) (p = 0.05). The LVAD alone group also had a greater mean postimplant length of hospitalization versus the concomitant procedures group (26.0 vs 19.0 days, p = 0.02). Finally, there was a trend toward improved survival for the group with concomitant tricuspid procedures versus LVAD alone. CONCLUSIONS For patients with significant TR undergoing implantable LVAD procedures, concomitant tricuspid procedures are associated with improved early clinical outcomes.

Neurocognitive function in destination therapy patients receiving continuous-flow vs pulsatile-flow left ventricular assist device support

BACKGROUND The HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow left ventricular assist device (LVAD) improved survival in destination therapy (DT) patients during a randomized trial compared with pulsatile-flow LVADs. This study documented changes in cognitive performance in DT patients from that trial to determine if there were differences between continuous-flow and pulsatile-flow support. METHODS Data were collected in a sub-study from 96 HeartMate II continuous-flow and 30 HeartMate XVE pulsatile-flow LVAD patients from 12 of the 35 trial sites that followed the same serial neurocognitive (NC) testing protocol at 1, 3, 6, 12, and 24 months after LVAD implantation. Spatial perception, memory, language, executive functions, and processing speed were the domains assessed with 10 standard cognitive measures. Differences over time and between LVAD type were evaluated with linear mixed-effects modeling. RESULTS From 1 to 24 months after LVAD implantation, changes in NC functions were stable or showed improvement in all domains, and there were no differences between the continuous-flow and pulsatile-flow groups. Data at 24 months were only available from patients with the continuous-flow LVAD due to the limited durability of the HeartMate XVE device. There was no decline in any NC domain over the time of LVAD support. Missing data not collected from patients who died could have resulted in a bias toward inflated study results. CONCLUSIONS The NC performance of advanced heart failure patients supported with continuous-flow and pulsatile-flow LVADs shows stabilization or improvement during support for up to 24 months.

Thrombolytic Therapy for Thrombosis of Continuous Flow Ventricular Assist Devices

BACKGROUND Despite chronic systemic anticoagulation, advanced heart failure patients treated with a continuous-flow left ventricular assist device (LVAD) remain at risk for pump thrombosis. Pump thrombosis may initially be suspected in the setting of clinical and biochemical evidence for intravascular hemolysis, putatively related to shear stress on red blood cells propelled through a partially occluded pump. Limited data exist to guide management in these patients. METHODS AND RESULTS We present a series of 8 LVAD patients who presented with intravascular hemolysis secondary to pump thrombosis who were treated with intraventricular thrombolytic therapy. In 3 patients, thrombolytic therapy led to complete and lasting resolution of hemolysis, suggesting successful dissolution of pump thrombus. In the remaining 5 patients, thrombolytic therapy ultimately failed to halt or reverse pump thrombosis and hemolysis: 1 patient required emergent pump exchange, 2 patients progressed to cardiogenic shock and died, 1 patient suffered a debilitating stroke after which care was withdrawn, and 1 patient underwent cardiac transplantation. CONCLUSIONS In the setting of LVAD thrombosis, thrombolytic therapy is an alternate treatment strategy in a subset of patients. Candidacy for this alternate procedure must carefully weigh the risks of complications, including hemorrhage and thromboembolism.

Presentation and management of left ventricular assist device inflow cannula malposition.

An unusual problem associated with the use of left ventricular assist devices (LVADs) relates to malposition of the apical inflow cannula. From 2005 to 2010, we implanted 154 continuous-flow HeartMate II (Thoratec, Pleasanton, CA) LVADs at our institution. In 4 separate instances, patients appeared to have malposition of the inflow cannula that resulted in serious symptoms. All 4 patients underwent surgery to reposition the cannula. Successful outcomes were achieved for 3 of the 4 patients.

Improved Early Survival With a Nonsternotomy Approach for Continuous-Flow Left Ventricular Assist Device Replacement

BACKGROUND Even in the modern era of continuous-flow left ventricular assist devices (CF LVADs), device replacement may be required. Nonsternotomy (NS) approaches are being used more commonly for replacement procedures. Outcomes after this less invasive approach compared with those after a reoperative sternotomy (RS) have not been extensively studied. Furthermore, the clinical impact of concurrent cardiac procedures during device replacement has not been examined. METHODS From 2005 to 2013, all consecutive implantable LVAD procedures were reviewed, and those using CF devices as both the initial and replacement device were identified. These CF LVAD replacement procedures were divided into those using an RS and those using an NS approach. Periprocedural morbidity and mortality were compared between the groups. RESULTS A total of 42 CF LVAD replacements were performed in 39 patients, with 20 using an RS approach and 22 using an NS approach. Eleven of the 20 replacement procedures performed by RS included a concurrent cardiac procedure. Relative to the RS cohort, the NS approach was associated with shorter cardiopulmonary bypass time, reduced length of mechanical ventilation, decreased transfusion requirements, less inotropic support, decreased incidence of right ventricular (RV) dysfunction, and shorter intensive care unit (ICU) and overall hospital stays. An NS approach was also associated with improved 30- and 90-day survival (100% versus 79.0% in the RS group; p = 0.048). RS replacement procedures appeared to be associated with increased morbidity, regardless of whether they included concurrent cardiac procedures. CONCLUSIONS Patients who did not require an RS approach and who underwent CF LVAD replacement through an NS approach had improved survival and reduced morbidity compared with those who required an RS.

Outcomes after implantable left ventricular assist device replacement procedures.

As the duration of support increases for patients with continuous flow left ventricular assist devices (LVADs), device replacement may still be necessary for a variety of indications. Outcomes after replacement LVAD surgeries have not been extensively described, and whether these patients experience outcomes similar to primary LVAD implant patients remains unclear. From 2003 to 2012, 342 consecutive implantable LVAD procedures took place at a single institution, of which 201 were considered destination therapy. Within this larger group, 30 patients underwent 35 replacement procedures. The three major indications for replacement LVAD procedures were mechanical/electrical failure (57%), hemolysis/thrombosis (29%), and infection (14%). Propensity matching using preoperative characteristics was used to generate a primary implant control group to determine the impact of the replacement status on outcomes. Thirty-day and 1-year survival after LVAD replacement was 90% and 48%, respectively. Survival outcomes were worse for patients undergoing device replacement compared with the matched primary cohort (p = 0.03). The need for transfusion and the incidence of postoperative right ventricular and renal dysfunction were similar between the two groups, as was length of hospitalization. There was no difference between the rates of postoperative infection or stroke. Emergent replacement procedures had a higher mortality than those done nonemergently. Given these findings, earlier timing for replacement, temporary stabilization with an extracorporeal device, and use of a nonsternotomy surgical approach should be investigated as strategies to improve outcomes.

Effectiveness of an Intervention Supporting Shared Decision Making for Destination Therapy Left Ventricular Assist Device: The DECIDE-LVAD Randomized Clinical Trial

Importance Shared decision making helps patients and clinicians elect therapies aligned with patients’ values and preferences. This is particularly important for invasive therapies with considerable trade-offs. Objective To assess the effectiveness of a shared decision support intervention for patients considering destination therapy left ventricular assist device (DT LVAD) placement. Design, Setting, and Participants From 2015 to 2017, a randomized, stepped-wedge trial was conducted in 6 US LVAD implanting centers including 248 patients being considered for DT LVAD. After randomly varying time in usual care, sites were transitioned to an intervention consisting of clinician education and use of DT LVAD pamphlet and video patient decision aids. Follow up occurred at 1 and 6 months. Main Outcomes and Measures Decision quality as measured by knowledge and values-choice concordance. Results In total, 135 patients were enrolled during control and 113 during intervention periods. At enrollment, 59 (23.8%) participants were in intensive care, 60 (24.1%) were older than 70 years, 39 (15.7%) were women, 45 (18.1%) were racial/ethnic minorities, and 62 (25.0%) were college graduates. Patient knowledge (mean test performance) during the decision-making period improved from 59.5% to 64.9% in the control group vs 59.1% to 70.0% in the intervention group (adjusted difference of difference, 5.5%; P = .03). Stated values at 1 month (scale 1 = “do everything I can to live longer…” to 10 = “live with whatever time I have left…”) were a mean of 2.37 in control and 3.33 in intervention (P = .03). Patient-reported treatment choice at 1 month favored LVAD more in the control group (than in the intervention group (47 [59.5%] vs 95 [91.3%], P < .001). Correlation between stated values and patient-reported treatment choice at 1 month was stronger in the intervention group than in the control group (difference in Kendall’s &tgr;, 0.28; 95% CI, 0.05-0.45); however, there was no improved correlation between stated values and actual treatment received by 6 months for the intervention compared with the control group (difference in Kendall’s &tgr;, 0.01; 95% CI, −0.24 to 0.25). The adjusted rate of LVAD implantation by 6 months was higher for those in the control group (79.9%) than those in the intervention group (53.9%, P = .008), with significant variation by site. There were no differences in decision conflict, decision regret, or preferred control. Conclusions and Relevance A shared decision-making intervention for DT LVAD modestly improved patient decision quality as measured by patient knowledge and concordance between stated values and patient-reported treatment choice, but did not improve concordance between stated values and actual treatment received. The rate of implantation of LVADs was substantially lower in the intervention compared with the control group. Trial Registration clinicaltrials.gov Identifier: NCT02344576

Graft vascular disease after cardiac transplantation and its relationship to mean acute rejection score

CONTEXT Graft vascular disease remains a significant source of morbidity and mortality in heart transplant patients. The influence of acute cellular rejection on the development of graft vascular disease is controversial. OBJECTIVE To determine the relationship between mean acute cellular rejection score and the presence of atherosclerosis or fibrointimal hyperplasia in cardiac allografts at autopsy. DESIGN This retrospective, autopsy-based study examined 27 heart transplant patients to evaluate for graft vascular disease. A rejection score for each patient was calculated as the average of all the rejection scores determined by endomyocardial biopsy. Gross and histologic examination of the heart was used to divide patients into 3 groups: no coronary artery disease, atherosclerosis, and fibrointimal hyperplasia. Mean rejection scores were calculated for each of these groups for all patients and patients who survived longer than 3 months. Mean rejection scores were compared by an analysis of variance and pairwise t tests. RESULTS Mean rejection scores demonstrated a trend of increasing value from no coronary disease (0.323) to atherosclerosis (0.569) to fibrointimal hyperplasia (0.835). Only fibrointimal hyperplasia had a significantly higher mean rejection score compared with patients with no coronary disease when examined in all patients (P = .01) and in patients who survived longer than 3 months (P = .049). CONCLUSION This study showed that the development of coronary artery fibrointimal hyperplasia, but not atherosclerosis, was significantly related to mean acute rejection score.