Stroke risk following implantation of current generation centrifugal flow left ventricular assist devices.

BACKGROUND AND AIM: Stroke remains a significant complication of left ventricular assist device (LVAD) therapy. We performed a single-center retrospective study evaluating patients undergoing first-time HeartWare HVAD (Medtronic Inc) or HeartMate 3 (Abbott Inc) implantation from September 2009-February 2018. METHODS: Exclusion criteria were age <18 and preoperative ECMO. The primary endpoint was stroke-free survival. Stroke was defined as new neurological deficits persisting >24 hours with corresponding radiographic evidence. Risk factors evaluated included demographics, medical comorbidities, heart failure etiology, LVAD indication, INTERMACS profile, and device type. Univariate predictors (P < .15) and variables clinically suspected to raise stroke risk were entered in a multivariate hazard regression model, specified using backward selection of covariates and accounting for competing risks of transplant/LVAD exchange. RESULTS: A total of 163 HVAD and 84 HM3 patients were analyzed. Median follow up (until death, censoring for transplant/LVAD removal, or end of follow up) was 1.2 years in HVAD patients and 1.4 years in HM3 patients. Stroke occurred in 24 HVAD patients (15 ischemic, 9 hemorrhagic) and 6 HM3 patients (4 ischemic, 2 hemorrhagic). One-year stroke-free survival was 76.8% for HVAD and 84.3% for HM3. Thirty-day mortality following stroke was 41.7% for HVAD and 66.7% for HM3; 54.2% of HVAD strokes were disabling compared to 83.3% of HM3 strokes. Age, LVAD indication, and device type were associated (P < .15) with stroke on univariate analysis. On multivariate analysis, the HVAD was associated with significantly higher stroke risk (hazard ratio, 2.57; 95% confidence interval, 1.02-6.44; P = .045). CONCLUSIONS: Different LVAD models appear to be associated with significantly different stroke risks.

Comorbidities and the decision to undergo or forego destination therapy left ventricular assist device implantation: An analysis from the Trial of a Shared Decision Support Intervention for Patients and their Caregivers Offered Destination Therapy for End-Stage Heart Failure (DECIDE-LVAD) study.

BACKGROUND: Patients considering destination therapy left ventricular assist devices (DT LVAD) often have high comorbid burden but the association between these comorbidities and post-decision outcomes is unknown. METHODS: We included subjects in DECIDE-LVAD (NCT02344576), a stepped-wedge multicenter trial of patients considering LVADs, recording comorbidities per INTERMACS protocol. We compared decisional conflict, regret, perceived stress, quality of life (EQ-VAS), depression (PHQ-2), struggle with- and acceptance of illness by comorbid burden and amongst the most common comorbidities. RESULTS: Of 239 patients, LVAD recipients (n = 164) and non-recipients (n = 75) had a similar proportion with ≥1 comorbidity (70% v. 80%, P = .09). Patients with comorbidities were younger regardless of LVAD implantation status. After adjusting for age, overall and amongst LVAD recipients, patients with ≥1 comorbidity had higher mean decision conflict at baseline (23.2 ±â€¯1.5 vs. 17.4 ±â€¯2.2), and at 6 months, higher stress (13.0 ±â€¯0.6 vs. 10.4 ±â€¯1.0) and struggle with illness (13.3 ±â€¯0.4 vs. 11.1 ±â€¯0.6) than those without comorbidities (P < .05). No difference was noted in decision regret, PHQ-2, EQ-VAS, acceptance of illness and survival overall and amongst LVAD recipients. Of the three most common comorbidities, while patients with pulmonary hypertension had worse decision regret, depression, stress and acceptance of illness at 6-month follow-up than those who did not have pulmonary hypertension, no difference was noted in patients with chronic renal disease or high body mass index. CONCLUSION: Patients considering LVAD implantation with comorbidities experience increased decision conflict, stress and struggle with illness. These findings provide insights in the role comorbidities play in patient decision-making and decisional outcomes.

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.

Characteristics of strokes associated with centrifugal flow left ventricular assist devices.

Stroke is a devastating complication of left ventricular assist device (LVAD) therapy. Understanding the characteristics, risk factors and outcomes of strokes associated with the centrifugal flow LVADs is important to devise better strategies for management and prevention. This is a retrospective cohort study at a single US academic medical center. The cohort includes patients who received a first time Heartmate 3 (HM3) or Heartware (HVAD) LVAD between September 2009 through February 2018 and had a stroke while the LVAD was in place. Descriptive statistics were used when appropriate. A logistic regression analysis was used to determine predictors of poor outcome. Out of a total of 247 patients, 12.1% (N = 30, 24 HVAD and 6 HM3) had a stroke (63% ischemic) and 3 of these patients had pump thrombosis. Events per patient year (EPPY) were similar for HVAD and HM3 patients (0.3 ± 0.1). INR was subtherapeutic in 47.4% of ischemic stroke patients and supratherapeutic in 18.2% of hemorrhagic stroke patients. Concurrent infections were more common in the setting of hemorrhagic stroke than ischemic stroke (45.4% vs 5.3%, p = 0.008). Strokes were severe in most cases, with initial NIH stroke scale (NIHSS) higher in HM3 patients compared to HVAD patients (mean 24.6 vs 16) and associated with high in-patient mortality (21.1% of ischemic stroke vs. 88.8% of hemorrhagic stroke). Predictors of death within 30 days and disability at 90 days included creatinine at stroke onset, concurrent infection, hemorrhaghic stroke, and initial stroke severity (NIHSS). A score derived from these variables predicted with 100% certainty mortality at 30 days and mRS ≥ 4 at 90 days. For patients with centrifugal flow LVADs, ischemic strokes were more common but hemorrhagic strokes were associated with higher in-patient mortality and more frequently seen in the setting of concurrent infections. Infections, sub or supratherapeutic INR range, and comorbid cardiovascular risk factors may all be contributing to the stroke burden. These findings may inform future strategies for stroke prevention in this population.

Implantable left ventricular assist devices: new hope for patients with end-stage heart failure.

INTRODUCTION: Recently, the Food and Drug Administration approved implantable left ventricular assist devices (LVAD) as destination therapy (DT) for end-stage heart failure patients who are ineligible for cardiac transplantation. OBJECTIVE AND STUDY DESIGN: This is a case series that describes the early results with DT LVAD at Duke University Medical Center (DUMC). An additional objective is to provide general information to a broad group of caregivers on this LVAD therapy, which is a new and developing treatment option. DATA SOURCE/COLLECTION METHODS: Pretreatment clinical condition and outcomes data were collected retrospectively on this cohort of patients through chart review. Outcomes in our patients are compared to data from prior studies and established databases. PRINCIPAL FINDINGS: Since approval of this therapy two years ago, 18 patients have been treated with implantable LVAD as DT at DUMC. The primary reason for ineligibility for transplant was advanced age (median age was 66). Nearly all of the patients (89%) were confined to the hospital requiring continuous inotropic infusions or temporary mechanical support (e.g., intra-aortic balloon pump) prior to LVAD. The 30-day survival following LVAD implantation was 94.5%; one-year survival was 60%. Eighty-nine percent of patients were successfully discharged to independent living. Operative mortality is similar to that of other cardiac surgery procedures performed on patients with advanced heart failure, while duration of intensive care stay and hospitalization remain considerably longer. PRINCIPAL LIMITATIONS: The principal limitation of this review is the absence of a control group of patients with end-stage heart failure who received conventional therapies. For this reason, the DT LVAD outcomes are compared to prior studies and database results. CONCLUSION: Implantable LVAD therapy provides new hope for end-stage heart failure patients who do not qualify for cardiac transplantation.

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.

Comparison of 2-Year Outcomes of Extended Criteria Cardiac Transplantation Versus Destination Left Ventricular Assist Device Therapy Using Continuous Flow.

Alternatives have emerged for patients ineligible for cardiac transplantation under standard criteria. The purpose of our study was to compare outcomes in patients ineligible for cardiac transplantation under standard criteria, treated either with extended criteria cardiac transplantation (ECCT) or a continuous flow destination therapy left ventricular assist device (CF DT-LVAD). From 2005 to 2012, patients treated with either ECCT or CF DT-LVAD at our institution were retrospectively analyzed. In the overall unmatched cohort, we examined mortality and other outcomes, including index hospitalization length of stay, renal function, stroke, and readmission rates. After propensity score (PS) matching, outcomes were compared between ECCT and CF DT-LVAD recipients. Overall, 62 patients underwent ECCT, and 146 patients were treated with CF DT-LVAD. The 2-year mortality estimate for ECCT recipients was 27.3% (95% confidence interval 15.5% to 39.1%) and for CF DT-LVAD recipients was 11.2% (95% confidence interval 4.8% to 17.6%). After PS matching of 39 patients from each treatment group, there was no significant difference in overall survival after 2 years (p = 0.346). In both unmatched and PS-matched analyses, CF DT-LVAD patients compared with ECCT had a significantly higher estimated glomerular filtration rate at 1 year but also had significantly higher hospital readmission rates. Stroke also more commonly occurred after CF DT-LVAD compared with ECCT (17 vs 5, unmatched; and 2 vs 1, PS matched). However, there was no significant difference between PS-matched groups in 2-year stroke-free survival (p = 0.371). In conclusion, ECCT and CF DT-LVAD in select patients are comparable therapies with respect to 2-year survival.

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.

Dysphagia in the setting of left ventricular assist device hemolysis.

A 69-year-old man with advanced heart failure treated with a continuous-flow left ventricular assist device presented for evaluation of dark urine and severe dysphagia. Because of evidence of ongoing intravascular hemolysis with device dysfunction, there was a clinical suspicion for pump thrombosis. He had progressive end-organ dysfunction and was therefore treated with tissue plasminogen activator with prompt resolution in hemolysis and dysphagia. Although symptoms of smooth muscle dystonia could represent worsening heart failure in the setting of device failure, the observation may also be related to intravascular hemolysis as described in the prototypic hemolytic disease, paroxysmal nocturnal hemoglobinuria.

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.

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.

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.

Heparin-induced thrombocytopenia in left ventricular assist device bridge-to-transplant patients.

BACKGROUND: The presence of heparin-induced thrombocytopenia (HIT) increases the risk for thromboembolic events in ventricular assist device (VAD) patients undergoing transplantation. However, cardiopulmonary bypass with alternative anticoagulants is often complicated by bleeding. Owing to this concern, we compared outcomes of HIT-positive versus control bridge-to-transplantation VAD patients; both groups were reexposed to heparin for cardiopulmonary bypass during transplant. METHODS: From February 2000 to January 2006, data were reviewed on 92 consecutive adult patients who underwent VAD placement as a bridge to transplantation. Patients in whom thrombocytopenia developed after heparin exposure were tested for HIT with an enzyme-linked immunosorbent assay for antiheparin/platelet factor-4 (HPF4) antibody (GTI Diagnostics, Waukesha, Wisconsin). During VAD support, heparin was avoided in HIT-positive patients, but all patients were reexposed to heparin during transplantation. Comparisons between HIT-positive and control patients for survival and freedom from thromboembolic events were determined using the Kaplan-Meier method and log-rank test. Continuous and categorical variables were compared using the Wilcoxon rank-sum and Student t test. RESULTS: Twenty-four of the 92 patients (26.1%) were determined to be HIT positive by enzyme-linked immunosorbent assay. Survival to transplant was not different between the two groups. When compared with control patients, HIT-positive patients who were reexposed to heparin had a greater decrease in platelet counts immediately after transplant (postoperative days 1 to 4, p < 0.05). Despite this transient thrombocytopenia, there was no difference in posttransplant mortality or thromboembolism. CONCLUSIONS: Heparin-induced thrombocytopenia-positive VAD patients did not experience increased thromboembolism or mortality after heparin reexposure. In light of the risks of using heparin alternatives, heparin reexposure is a safe management strategy for HIT-positive VAD patients.

Left ventricular assist device as destination therapy in doxorubicin-induced cardiomyopathy.

Doxorubicin-induced cardiomyopathy is not uncommon and may progress to end-stage heart failure. Treatment of this condition with heart transplantation, however, requires that the primary malignancy be deemed "cured." We present the case of a 55- year-old woman who had doxorubicin-induced cardiomyopathy and non-Hodgkin's lymphoma. The active status of her lymphoma precluded heart transplantation. She had end-stage heart failure and underwent the insertion of a left ventricular assist device as a destination therapy.