Circulatory support with implantable left ventricular assist devices (LVADs) is an important treatment option for patients with advanced-stage heart failure. Over the past decade, the continuous-flow HeartMate II LVAD (Thoratec Corporation, Pleasanton, CA) has been studied in multicenter clinical trials and subsequently gained commercial approval by the US Food and Drug Administration for the indications of bridge-to-transplant (BTT) and destination therapy (DT).1–3 Continued clinical research has guided refinements in patient selection, patient care protocols, timing of device implantation, and technical improvements with the LVAD system.4 As a result of these research efforts, adverse event rates have declined considerably and outcomes continue to improve with survival rates of 85% at 1 year for patients with BTT and as high as 80% at 2 years in select patients supported for DT.5–7
The original HeartMate I series of LVADs (implanted pneumatic and vented electric) incorporated a porous woven polyester graft material within the inflow and outflow valved conduits and for the outflow graft.8 The original HeartMate II LVAD used the same graft material for the outflow graft and within the inflow conduit for some flexibility. The durability and biocompatibility of this graft material proved to be excellent, but it required a process of preclotting at the time of implantation and excessive bleeding from the graft was seen in some patients with coagulopathies.9 In 2010, a sealed graft was introduced for use with the HeartMate II to eliminate preclotting procedures and to reduce operative bleeding. At the same time, a snap ring on the outflow graft bend relief was incorporated. Questions have been raised among users whether these changes have resulted in an increase in thrombotic events. This study was conducted to assess the differences in operative bleeding rates, thromboembolism, related complications, and short-term outcomes in patients undergoing HeartMate II implantation with a sealed or nonsealed graft.
We retrospectively reviewed data from patients who underwent implantation with the HeartMate II LVAD between May 2009 and December 2011. The study was approved by our Institutional Review Board. Patients were assigned to one of two groups based on the type of graft material incorporated into the conduits (inflow and outflow), which was determined by the date that the manufacturer exchanged the HeartMate II devices at our institution. The nonsealed porous graft group (NS-graft) consisted of 67 consecutive patients who underwent implantation between May 1, 2009 and October 21, 2010. The sealed graft group (S-graft) included 65 patients implanted with the LVAD consecutively from February 8, 2011 to December 31, 2011. Patients implanted with the HeartMate II between October 21, 2010 and February 8, 2011 were not included in this analysis because the devices used had only sealed outflow grafts and nonsealed inflow conduits. Also, 14 patients who underwent exchange from a HeartMate XVE to a HeartMate II were excluded from the analysis.
Anticoagulation therapy after implant included intravenous heparin after chest tube drainage was less than 50 ml/hour and was titrated to achieve a partial thromboplastin time of 45 seconds. Once the chest tubes were removed and the patient was extubated, warfarin, aspirin (81 mg), and dipyridomol (75 mg thrice daily) were started with a target international normalized ratio of 1.5–2.5. This anticoagulation protocol was maintained throughout the entire study period. The mean arterial blood pressure was maintained between 65 and 75 mm Hg to optimize LVAD output and to aid in avoiding hemorrhagic stroke. None of the patients included in this study had a history of stroke.
For the purposes of this study, demographics, baseline laboratory values, postoperative hemoglobin and lactate dehydrogenase (LDH) levels, cardiopulmonary bypass time, blood product transfusions, intensive care unit (ICU) time, duration of postoperative mechanical ventilation, as well as infection rate of the implanted components or driveline exit site, stroke rate during the 6-month follow-up, and 30-day survival after LVAD implantation were compared between the two groups.
Continuous variables were expressed as the mean ± standard deviation and categorical variables as percentages. The two-tailed unpaired t-test was used to compare mean values of the two groups. Comparisons of categorical variables were made by use of a χ2 test without Yates correction for continuity. If the expected number in any given data subgroup was less than 5, the Fisher’s exact test was used. Paired t-test was used to analyze changes of variables over time. Differences were considered statistically significant when the p value was less than 0.05.
Two study groups were comparable in terms of preoperative demographics, clinical status, and laboratory characteristics (Tables 1and2). Blood product transfusions were required significantly less often in the S-graft group than that in the NS-graft group (Table 3), whereas the hemoglobin levels were comparable (Figure 1). The LDH values were not statistically different between the S-group and NS-group through the 6-month follow-up period (Figure 2). However, 24 hours after implantation, the increase in LDH levels from the levels before LVAD implantation was significantly larger in the NS-graft group (537 ± 255 U/L from 429 ± 345 U/L, p = 0.0013) in contrast to S-graft group where the increase did not reach significance (452 ± 164 from 381 ± 302 U/L, p = 0.1117).
The time of cardiopulmonary bypass for implantation was longer for the NS-graft group (101 ± 37 minutes) than that for the S-graft group (88 ± 36 minutes), but this difference was not significant (p = 0.103). The total ICU days were significantly longer in the NS-graft group (32 ± 29 vs. 21 ± 17 days, p = 0.026) than that in the S-graft group. Time on mechanical ventilation was also longer in the NS-graft group (117 ± 130 vs. 70 ± 52 hours, p = 0.0196) than that in the S-graft group. There were no device-related infections in the S-graft group, but the NS-graft group had one driveline infection at 66 days postimplant. No strokes occurred in the S-graft group as compared with four (6%) in the NS-graft group that occurred between 4 and 75 days after LVAD implantation, p = 0.056. There were three ischemic strokes and one hemorrhagic stroke. The 30-day survival rate was not significantly different between groups (p = 0.053), but the proportion alive favored the S-graft group (65/67, 97%) over the NS-graft group (57/65, 88%).
This study shows that the use of sealed grafts in the HeartMate II in our patients resulted in a significant decrease in the requirement for blood product transfusion, lower postimplantation increase in LDH values, shortened duration of mechanical ventilation, and shorter ICU stay. Furthermore, there was a trend toward decreased incidence of strokes which might be explained by more compatible surface and blood flow and less variables connected with preclotting the grafts, that is, debris formation. Also, increased blood transfusion precipitates activation of inflammation and coagulation; a response connected to increased morbidity and length of stay. Our center’s data therefore show that the use of the sealed grafts in the HeartMate II helped to reduce the overall postoperative morbidity in our patients.
The changes from a porous nonsealed graft to a sealed graft with bend relief and snap connector in the HeartMate II LVAD were intended to provide more efficient preparation of the device and to eliminate variability associated with preclotting techniques. The original porous graft material used in the HeartMate devices required preclotting to prevent bleeding from the grafts at the time of implant. Various methods were used to seal the graft and included clotting of whole blood on the exterior surface, application of bio-glue, or soaking of the graft in plasma followed by baking in an autoclave to achieve protein coagulation. This process may delay device preparation and increases the risk for debris within the graft that may embolize during support. The results of the different graft clotting methods were variable and may have contributed to bleeding and thrombotic events. Incorporation of a gelatin-impregnated “sealed graft” eliminates this process and does not alter function of the LVAD. The sealed graft impregnated with gelatin has been used extensively and was not considered to be a major change in the device.10,11 The gelatin-impregnated grafts have been used in cardiovascular surgery for many years with universal acceptance. The change of graft material in the HeartMate device is another enhancement that should result in a further reduction in adverse events.
With the change in graft material, a new snap ring on the graft bend relief was incorporated to facilitate easier attachment at the pump. Detachments of the snap ring have been reported, but did not occur in the group of patients included in this report.12 Meticulous inspection to the outflow graft connector must be completed after the initial attachment, once the LVAD is operating, and just before closure of the chest a clip is attached to assure that detachment does not occur during support. Although some users have previously suggested that presealed HeartMate II graft changes have resulted in an increase of thromboembolic complications, in our experience, there has been a reduction in these adverse events.
Postoperative bleeding is a complication that is a major contribution to serious infection episodes. Bleeding increases the number of reoperations, increases exposure with a longer ICU stay, longer intubation and mechanical ventilation time, and blood draws; all contributors to the worse morbidity and mortality. Fewer bleeding episodes in our patients did show fewer infection events and overall better outcomes.
This study is limited by the single-center experience and was not controlled or randomized.
In our study, use of sealed rather than a nonsealed graft material in the inflow and outflow conduits of the HeartMate II resulted in decreased usage of blood products during LVAD implantation and was not associated with an increase in adverse events. There was a trend for patients with the sealed graft to have fewer stroke events when compared with LVADs with nonsealed grafts.
1. Miller LW, Pagani FD, Russell SD, et al.HeartMate II Clinical Investigators. Use of a continuous-flow device in patients awaiting heart transplantation. N Engl J Med. 2007;357:885–896
2. Pagani FD, Miller LW, Russell SD, et al.HeartMate II Investigators. Extended mechanical circulatory support with a continuous-flow rotary left ventricular assist device
. J Am Coll Cardiol. 2009;54:312–321
3. Slaughter MS, Rogers JG, Milano CA, et al.HeartMate II Investigators. Advanced heart failure treated with continuous-flow left ventricular assist device
. N Engl J Med. 2009;361:2241–2251
4. Slaughter MS, Pagani FD, Rogers JG, et al. Clinical management of continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant. 2010;29:S1–S39
5. Starling RC, Naka Y, Boyle AJ, et al. Results of the post-U.S. Food and Drug Administration-approval study with a continuous flow left ventricular assist device
as a bridge to heart transplantation: A prospective study using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol. 2011;57:1890–1898
6. John R, Naka Y, Smedira NG, et al. Continuous flow left ventricular assist device
outcomes in commercial use compared with the prior clinical trial. Ann Thorac Surg. 2011;92:1406–1413; discussion 13
7. Kirklin JK, Naftel DC, Pagani FD, et al. Long-term mechanical circulatory support (destination therapy): On track to compete with heart transplantation? J Thorac Cardiovasc Surg. 2012;144:584–603; discussion 597
8. Maher TR, Butler KC, Poirier VL, Gernes DB. HeartMate left ventricular assist devices: A multigeneration of implanted blood pumps. Artif Organs. 2001;25:422–426
9. Goldstein DJ, Beauford RB. Left ventricular assist devices and bleeding: Adding insult to injury. Ann Thorac Surg. 2003;75(6 suppl):S42–S47
10. Trudell LA, Whittemore AD, Sunwoo MH. The performance of commercially available sealed Dacron vascular grafts in intraarterial thrombolytic therapy. ASAIO J. 1995;41:M633–M635
11. Reid DB, Pollock JG. A prospective study of 100 gelatin-sealed aortic grafts. Ann Vasc Surg. 1991;5:320–324
12. Agarwal R, Adatya S, Uriel N, Jorde UP. Clinical impact, diagnosis, and management of a disconnected outflow graft bend relief in a patient supported by the HeartMate II left ventricular assist system. J Heart Lung Transplant. 2012;31:1238–1239
Keywords:Copyright © 2014 by the American Society for Artificial Internal Organs
left ventricular assist device; sealed and nonsealed graft on the inflow and outflow conduits