K. Liao

Gastrointestinal bleeding rates in recipients of nonpulsatile and pulsatile left ventricular assist devices

OBJECTIVE Pulsatile and nonpulsatile left ventricular assist devices are effective in managing congestive heart failure. Despite early evidence for clinical efficacy, the long-term impact of nonpulsatile flow on end-organ function remains to be determined. Our goal was to compare rates of gastrointestinal bleeding in nonpulsatile and pulsatile device recipients. METHODS In a retrospective review of 101 left ventricular assist device recipients (55 nonpulsatile, 46 pulsatile) from October 31, 2003, to June 1, 2007, at a single center, gastrointestinal bleeding was defined as guaiac-positive stool with hemoglobin drop requiring transfusion of at least 2 units of packed red blood cells. To assess bleeding risk outside the initial postoperative course, any patients with a device in place for 15 days or less was excluded. RESULTS Twelve nonpulsatile and 3 pulsatile left ventricular assist device recipients had gastrointestinal bleeding 16 days or longer after device implantation. The event rates were 63 events/100 patient-years for nonpulsatile devices and 6.8 events/100 patient-years for pulsatile devices (P = .0004). This difference persisted for bleeding occurring 31 days or longer after device implantation, with 46.5 events/100 patient-years for nonpulsatile devices versus 4.7 events/100 patient-years for pulsatile devices (P = .0028). Mortalities were similar between groups (15% nonpulsatile vs 17% pulsatile, P = .6965). CONCLUSION Patients with nonpulsatile left ventricular assist devices appear to have a higher rate of gastrointestinal bleeding events than do pulsatile left ventricular assist device recipients. Further prospective evaluation is needed to determine potential etiologies and strategies for reducing gastrointestinal bleeding in this population.

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.

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.

Derivation and High Engraftment of Patient-Specific Cardiomyocyte-Sheet Using Induced Pluripotent Stem Cells Generated From Adult Cardiac Fibroblast

Background—Induced pluripotent stem cells (iPSCs) can be differentiated into potentially unlimited lineages of cell types for use in autologous cell therapy. However, the efficiency of the differentiation procedure and subsequent function of the iPSC-derived cells may be influenced by epigenetic factors that the iPSCs retain from their tissues of origin; thus, iPSC-derived cells may be more effective for treatment of myocardial injury if the iPSCs were engineered from cardiac-lineage cells, rather than dermal fibroblasts. Methods and Results—We show that human cardiac iPSCs (hciPSCs) can be generated from cardiac fibroblasts and subsequently differentiated into exceptionally pure (>92%) sheets of cardiomyocytes (CMs). The hciPSCs passed through all the normal stages of differentiation before assuming a CM identity. When using the fibrin gel–enhanced delivery of hciPSC-CM sheets at the site of injury in infarcted mouse hearts, the engraftment rate was 31.91%±5.75% at Day 28 post transplantation. The hciPSC-CM in the sheet also appeared to develop a more mature, structurally aligned phenotype 28 days after transplantation and was associated with significant improvements in cardiac function, vascularity, and reduction in apoptosis. Conclusions—These data strongly support the potential of hciPSC-CM sheet transplantation for the treatment of heart with acute myocardial infarction.

Catheter ablation of hemodynamically unstable ventricular tachycardia with mechanical circulatory support

BACKGROUND Catheter ablation of hemodynamically unstable ventricular tachycardia (VT) is possible with mechanical circulatory support (MCS), little is known regarding the relative safety and efficacy of different supporting devices for such procedures. METHODS AND RESULTS Sixteen consecutive patients (aged 63 ± 11 years with left ventricular ejection fraction of 20 ± 9%) who underwent ablation of hemodynamically unstable VT were included in this study. Hemodynamic support included percutaneous (Impella® 2.5, n = 5) and implantable left ventricular assist devices (LVADs, n = 6) and peripheral cardiopulmonary bypass (CPB, n = 5). Except for 2 Impella cases, hemodynamic support was adequate (with consistent mean arterial pressure of > 60 mmHg) to permit sufficient activation mapping for ablation. In the Impella and CPB groups, mean time under hemodynamic support was 185 ± 86 min, and time in VT was 78 ± 36 min. Clinical VT could be terminated at least once by ablation in all patients except 1 case with Impella due to hemodynamic instability. Peri-procedural complications included hemolysis in 1 patient with Impella and surgical intervention for percutaneous Impella placement problems in another 2. The median number of appropriately delivered defibrillator therapies was significantly decreased from 6 in the month before VT ablation to 0 in the month following ablation (p = 0.001). CONCLUSIONS Our data suggest that peripheral CPB and implantable LVAD provide adequate hemodynamic support for successful ablation of unstable VT. Impella® 2.5, on the other hand, was associated with increased risk of complications, and may not provide sufficient hemodynamic support in some cases.

Timing of transesophageal echocardiography in diagnosing patent foramen ovale in patients supported with left ventricular assist device

Left ventricular assist devices unload the left ventricle and decrease left atrial pressure. This hemodynamic change may cause a right to left atrial shunt and hypoxemia in patients with patent foramen ovale. We prospectively studied the best time for performing diagnostic transesophageal echocardiography in left ventricular assist device patients. Intraoperative transesophageal echocardiography was performed in 14 patients before cardiopulmonary bypass was initiated and after left ventricular assist device was implanted. No patent foramen ovale was detected when transesophageal echocardiography was done before bypass, but a patent foramen ovale was found in 3 patients when transesophageal echocardiography was performed after left ventricular assist device was activated. Patent foramen ovale was confirmed by inspection in all three patients and surgically closed during the same procedure. There were no patent foramen ovale closure-related complications.