Forum Kamdar

Improved Survival and Decreasing Incidence of Adverse Events With the HeartMate II Left Ventricular Assist Device as Bridge-to-Transplant Therapy

BACKGROUND Pulsatile left ventricular assist devices (LVADs) are effective as bridge-to-transplant therapy, but they are limited by their large size and lack of durability. Smaller, more durable, continuous flow devices such as the HeartMate II LVAD are increasingly being used. The aim of this study is to report our single-center experience with this device as bridge-to-transplant therapy. METHODS Overall, 47 patients received HeartMate II LVADs at our center from June 2005 to July 2007; 32 as bridge to transplant, 7 as destination therapy, and 8 as exchange therapy for a failed HeartMate XVE. We reviewed our experience with the device as bridge-to-transplant therapy and report on patient survival and adverse events. RESULTS The mean age of the bridge-to-transplant patients was 50.75 +/- 13.78 years; 10 (31.3%) were female. The cause of the underlying disease was ischemic in 18 patients (56.3%), idiopathic in 11 (34.4%), myocarditis in 1 (3.1%), postpartum cardiomyopathy in 1 (3.1%), and congenital heart disease in 1 (3.1%). The mean duration of HeartMate II support was 193.2 +/- 139.9 days. At 30 days after HeartMate II placement, the patient survival was 96.9% by Kaplan-Meier analysis; at 6 months (alive or transplanted), 86.9%. Major adverse events included bleeding requiring reexploration in 5 patients (15.6%), right ventricular failure requiring right ventricular assist device support in 2 (6.3%), LVAD-related infections in 4 (12.5%), neurologic or thromboembolic events in 2 (6.3%), and gastrointestinal bleeding in 5 (15.6%). We noted one serious device malfunction (3.1%) resulting in the patients death; in addition, 2 patients experienced pump thrombosis (6.3%). CONCLUSIONS Despite morbidity, use of the HeartMate II LVAD as bridge-to-transplant therapy is associated with excellent survival and low mortality rates. We found a marked decrease in morbidity related to right ventricular failure, to device-related infections, and to thromboembolic events. However, the requirements for anticoagulation therapy may be associated with increased mediastinal and gastrointestinal bleeding. Strategies to optimize anticoagulation therapy may further improve results for these critically ill patients.

Low thromboembolic risk for patients with the Heartmate II left ventricular assist device

OBJECTIVE Thromboembolic events can occur in up to 20% of patients with a left ventricular assist device. The aggressive use of anticoagulation with newer continuous-flow devices has potentially increased the risk of postoperative bleeding. The predecessor of the HeartMate II left ventricular assist device, the HeartMate XVE (Thoratec Corp, Pleasanton, Calif), was associated with an extremely low thromboembolic risk, even without anticoagulation, because of its unique textured surfaces. Even though several areas of the HeartMate II are textured, a protocol was adopted for this new axial flow pump requiring long-term anticoagulation with warfarin. In our study, we investigated whether the HeartMate II left ventricular assist device is associated with a similarly low thromboembolic risk as the HeartMate XVE. METHODS At our institution, 45 patients (mean age, 57.24 +/- 14.2 years) underwent implantation of the HeartMate II; 30 underwent bridge-to-transplantation therapy, 7 underwent destination therapy, and 8 underwent left ventricular assist device exchange for a failed XVE left ventricular assist device. Total duration of HeartMate II support was 352.13 patient-months (mean duration, 7.2 +/- 5.2 months). All 45 patients were treated postoperatively with warfarin and aspirin. We recorded use of these 2 medications and monthly international normalized ratios. Prospectively, we also monitored patients for any clinical thromboembolic events and for pump thrombus. RESULTS Of our 45 study patients, 41 had a mean international normalized ratio of less than 2.0; of those 41 patients, 21 had a mean international normalized ratio of less than 1.6. Because of recurrent gastrointestinal bleeding episodes, 7 patients discontinued warfarin for a total duration of 39.1 patient-months. During the entire period of HeartMate II support, we noted 1 thromboembolic event. In addition, another patient had a suspected left ventricular assist device pump thrombus that resolved with a high-intensity heparin anticoagulation protocol (international normalized ratio, 1.3). CONCLUSIONS Our preliminary single-center analysis suggests that the HeartMate II is associated with an extremely low thromboembolic risk and with less stringent requirements for anticoagulation. Selected patients at high risk for bleeding can be safely followed with either no or extremely low anticoagulation requirements for prolonged periods.

Effects of Centrifugal, Axial, and Pulsatile Left Ventricular Assist Device Support on End-Organ Function in Heart Failure Patients

PURPOSE Newer continuous-flow left ventricular assist devices (LVAD) have the advantage of smaller size and increased durability. Questions remain regarding the safety and effects of long-term nonpulsatile flow, despite some animal and human studies showing that end-organ function is well maintained with pulsatile or axial-flow devices. This study investigated whether centrifugal devices have similar effects on end-organ function. METHODS All patients who underwent LVAD implantation as bridge-to-transplant (BTT) therapy from January 2004 through May 2007 were reviewed. Excluded were patients on biventricular support, destination therapy, temporary support, and patients who died within 30 days after LVAD implantation. The centrifugal device was the VentrAssist (Ventracor Ltd, Sydney, Australia); axial, the HeartMate II; and pulsatile, the HeartMate XVE (Thoratec Corp, Pleasanton, CA). RESULTS During the study, 10 VentrAssist, 30 HeartMate II, and 18 HeartMate XVE devices were implanted. Among the 3 groups, age, gender, weight, duration of LVAD support, and cause of heart failure were comparable. No significant differences were found between groups with respect to baseline renal function, hepatic function, or hematologic function. At 1 and 3 months of follow-up, renal and hepatic function either improved or remained within normal limits in all groups. CONCLUSIONS Centrifugal, axial, and pulsatile LVADs all provide adequate circulatory support to maintain appropriate end-organ function in patients with end-stage heart failure. The advantages of the newer continuous-flow devices can be safely applied to an increasing number of patients. Long-term studies (>1 year) are needed to assess effects on end-organ function with continuous-flow devices, which may have important implications for use as destination therapy.

Effects of the HeartMate II continuous-flow left ventricular assist device on right ventricular function

BACKGROUND Continuous-flow devices have become the standard of care for mechanical circulatory support for end-stage heart failure patients because of improved survival and durability. The effects of these devices, such as the HeartMate II (HMII) left ventricular assist device (LVAD), on right ventricular (RV) function have not been evaluated in detail. This study evaluated the incidence of RV failure, alterations in RV function, severity of tricuspid regurgitation (TR), and cardiac hemodynamics after HMII implantation. METHODS Echocardiograms (n = 22) and right heart catheterizations (n = 40) were performed before and after 4 to 6 months of HMII support in 40 bridge-to-transplant patients. Right heart failure was defined as the requirement for inotropes and/or nitric oxide requirement after LVAD implantation for >14 days or the need for right-sided mechanical circulatory support. RESULTS Overall, RV failure after HMII implantation occurred in 2 of 40 patients (5%). Significant improvements occurred in cardiac index, with reductions in right atrial pressure, RV stroke work index, tricuspid annular motion, mean pulmonary artery pressure, and pulmonary vascular resistance after HMII support. There was a trend towards reduction in TR after LVAD support (p = 0.075). CONCLUSIONS The incidence of RV failure after support with continuous-flow devices such as the HMII is low. The favorable effects of the HMII on cardiac hemodynamics result in improved RV function, improved right- and left-sided hemodynamic profiles, and a reduction in TR severity. These findings may have important implications for LVAD patients needing longer-term support.

Lessons Learned From Experience With Over 100 Consecutive HeartMate II Left Ventricular Assist Devices

BACKGROUND Continuous-flow left ventricular assist devices (LVADs) such as the HeartMate II have become the therapy of choice in patients with end-stage heart failure. The aim of this study is to report the outcomes in patients receiving the HeartMate II LVAD at a single center and review the lessons learned from this experience. METHODS From June 2005 to June 2010, 130 consecutive patients received the HeartMate II LVAD. Of these, 102 were bridge-to-transplant (BTT), 17 destination therapy, and 11 exchanges for failed HeartMate XVE. This study focuses on the 102 BTT patients. The HeartMate II was approved by the US Food and Drug Administration (FDA) as BTT in April 2008 and 64 patients received this device as BTT since that date. We review our experience with the device as BTT and report on patient survival and adverse events as well as the impact of FDA approval on outcomes. RESULTS Overall, mean age was 52.6 ± 12.8 years; 26 (25.5%) were female. Disease etiology was ischemic in 58, nonischemic in 36, and other in 8. Overall, 30-day, 6-month, and 1-year survival for the BTT patients was 95.1%, 83.5%, and 78.8%, respectively. The 6-month survival in 38 patients in the clinical trial (pre-FDA) was 88.8% and was not statistically significant compared with the 76.2% 6-month survival in the 64 patients in the post-FDA approval period (p value = 0.1). Major adverse events among the 102 BTT patients included right ventricular failure in 5 (4.9%), LVAD driveline infections in 25 (24.5%), neurologic events in 10 (9.8%), and gastrointestinal bleeding in 18 (17.6%) patients. In addition, 1 patient (0.98%) had pump thrombus requiring device replacement. CONCLUSIONS Despite significant morbidity, use of the HeartMate II LVAD as BTT provides excellent hemodynamic support and is associated with excellent survival and low mortality. In addition, there needs to be improvement and focused strategies in the areas of gastrointestinal bleeding, driveline infections, and adverse neurologic events for these devices to be able to provide a real long-term alternative to heart transplantation.

Effects on pre- and posttransplant pulmonary hemodynamics in patients with continuous-flow left ventricular assist devices

OBJECTIVE Pulsatile left ventricular assist devices have been shown to effectively reduce pulmonary hypertension in patients with end-stage heart failure. However, it remains to be seen whether newer continuous-flow left ventricular assist devices have a similar effect on pulmonary hypertension. The objective of this study was to determine whether the HeartMate II (Thoratec Corp, Pleasanton, Calif), a continuous-flow left ventricular assist device, is effective in improving pulmonary hemodynamics in the period after left ventricular assist device support and posttransplant. METHODS Fifty patients with end-stage heart failure underwent HeartMate II left ventricular assist device placement as a bridge to transplant. We evaluated their pulmonary hemodynamics with right-sided heart catheterization at baseline, after left ventricular assist device placement, and after heart transplant. RESULTS The mean age of patients was 53.7 +/- 13.5 years. Ischemic etiology was present in 60% of the patients. After left ventricular assist device placement (mean duration, 135 +/- 60 days), mean systolic and diastolic pulmonary artery pressures decreased significantly from a baseline of 55.2 +/- 13.4 mm Hg and 27.3 +/- 6.8 mm Hg, respectively, to 35.9 +/- 10.8 mm Hg and 15.8 +/- 6.5 mm Hg, respectively (P < .001). Similarly, mean pulmonary vascular resistance decreased significantly from a baseline of 3.6 +/- 1.9 Woods units to 2.1 +/- 0.8 Woods units (P < .001). Posttransplant pulmonary hemodynamics also remained within normal limits, even in patients with previously severe pulmonary hypertension. CONCLUSION Continuous-flow left ventricular assist devices effectively improve pulmonary hemodynamics associated with end-stage heart failure. Moreover, pulmonary hemodynamics remain within normal limits in the posttransplant period, even in patients with severe pulmonary hypertension. Therefore, adequate left ventricular decompression achieved with newer left ventricular assist devices can reverse significant pulmonary hypertension in patients with end-stage heart failure, making them eligible for cardiac transplantation.

Postcardiac transplant survival in the current era in patients receiving continuous-flow left ventricular assist devices.

OBJECTIVES Continuous-flow left ventricular assist devices have become the standard of care for patients with heart failure requiring mechanical circulatory support as a bridge to transplant. However, data on long-term post-transplant survival for these patients are limited. We evaluated the effect of continuous-flow left ventricular assist devices on postcardiac transplant survival in the current era. METHODS All patients who received a continuous-flow left ventricular assist device as a bridge to transplant at a single center from June 2005 to September 2011 were evaluated. RESULTS Of the 167 patients who received a continuous-flow left ventricular assist device as a bridge to transplant, 77 (46%) underwent cardiac transplantation, 27 died before transplantation (16%), and 63 (38%) remain listed for transplantation and continued with left ventricular assist device support. The mean age of the transplanted patients was 54.5 ± 11.9 years, 57% had an ischemic etiology, and 20% were women. The overall mean duration of left ventricular assist device support before transplantation was 310 ± 227 days (range, 67-1230 days). The mean duration of left ventricular assist device support did not change in patients who had received a left ventricular assist device in the early period of the study (2005-2008, n = 62) compared with those who had received a left ventricular assist device later (2009-2011, n = 78, 373 vs 392 days, P = NS). In addition, no difference was seen in survival between those patients supported with a left ventricular assist device for fewer than 180 days or longer than 180 days before transplantation (P = NS). The actuarial survival after transplantation at 30 days and 1, 3, and 5 years by Kaplan-Meier analysis was 98.7%, 93.0%, 91.1%, and 88.0%, respectively. CONCLUSIONS The short- and long-term post-transplant survival for patients bridged with a continuous-flow left ventricular assist device in the current era has been excellent. Furthermore, the duration of left ventricular assist device support did not affect post-transplant survival. The hemodynamic benefits of ventricular unloading with continuous-flow left ventricular assist devices, in addition to their durability and reduced patient morbidity, have contributed to improved post-transplant survival.

N-terminal pro B-type natriuretic peptide predicts mortality in patients with left ventricular hypertrophy

BACKGROUND Left ventricular hypertrophy adversely affects outcomes in patients with hypertension. Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) adds incremental prognostic information in patients with hypertension and left ventricular hypertrophy (LVH) is not well established. We aimed to study the prognostic value of NT-proBNP in hypertensive patients with LVH. METHODS Echocardiography was performed in 232 patients (mean age 61±15, 102 males, 130 females) for the diagnosis of left ventricular hypertrophy. Left ventricular mass was measured according to The American Society of Echocardiography guidelines. A blood sample was taken for NT-proBNP determination. NT-proBNP levels were analyzed in quartiles after log transformation. Long term survival was established by review of electronic medical records. RESULTS Arterial hypertension was present in 130 patients (56%) and left ventricular hypertrophy was present in 105 patients (45%). In patients with left ventricular hypertrophy, NT-proBNP levels predicted long term survival (Chi-square=10, p=0.01). After adjusting by age, presence of coronary artery disease, ejection fraction, diabetes status, and hypertension; patients in highest NT pro-BNP quartile were twice as likely to die when compared to patients in the lowest NT-ptoBNP quartile (OR=2.2, 95% CI=1.0-4.6, p=0.03). CONCLUSION NT-proBNP is an independent predictor of survival in patients with hypertension and increased left ventricular mass.

Safety of discontinuation of anti-coagulation in patients with continuous-flow left ventricular assist devices

Continuous-flow left ventricular assist devices (CF-LVADs) are standard therapy for end-stage heart failure given their efficacy and durability. However, to prevent thrombotic device-related complications, these devices require systemic anti-coagulation and anti-platelet therapy. This can result in significant bleeding episodes, such as gastrointestinal bleeding and epistaxis, occurring in 15% to 45% of cases and occasionally warranting discontinuation of such therapy. The incidence of thrombotic complications, including pump thrombosis, neurologic complications and peripheral thromboembolic events, has been relatively low, ranging from 0% to 7% in large multicenter trials. Because bleeding complications predominate among the adverse events in patients with continuous-flow LVADs, major bleeding may occasionally warrant discontinuation of anti-coagulation therapy. The incidence of stopping anti-coagulation for prolonged periods and the safety profile with regard to thromboembolic complications in CF-LVAD patients has not been adequately described. We reviewed all patients receiving a CF-LVAD from June 2005 to October 2011 at the University of Minnesota. CF pumps included the HeartMate II (Thoratec, Pleasanton, CA), VentrAssist (Ventracor, Australia) and HVAD (HeartWare, Framingham, MA). Any patients whose anti-coagulation or anti-coagulation and anti-platelet therapy was discontinued for 430 days were included in the analysis. Patients with only temporary or biventricular mechanical circulatory support and patients who died within 30 days of LVAD placement were excluded from the analysis. We collected baseline and follow-up data, including patient characteristics, history of atrial fibrillation, history of heparin-induced thrombocytopenia, renal function at time of discontinuation, LVAD speed at time of discontinuation, and aortic valve opening on echocardiography within 3 months of discontinuation of anti-coagulation, anti-platelet and anti-coagulation use, and anti-coagulation hematologic parameters. After patients were discharged from the hospital, they

Pulmonary Arterial Hypertension in von Recklinghausen's Disease

A 69-year-old woman with von Recklinghausen’s disease (neurofibromatosis type 1) was evaluated for syncope. Physical examination revealed characteristic axillary freckling, café-au-lait macules, and innumerable sessile cutaneous tumors on the trunk (Figure A). Echocardiography showed marked right ventricular dilatation and reduced right ventricular function (Figure B and Video 1). Invasive hemodynamic evaluation was consistent with pulmonary arterial hypertension. The mean pulmonary artery pressure and the pulmonary artery wedge pressure measured at rest were 39 and 3 mm Hg, respectively. The calculated pulmonary vascular resistance was 23 Wood units (normal, <2 Wood units). There was no response to pulmonary vasoreactivity testing with inhaled nitric oxide.