The outcomes of overall (beyond CentriMag support) treatment of cardiorespiratory indication up to follow-up of 1 year are provided in the Supplemental Digital Content (http://links.lww.com/ASAIO/A49). Due to limited number of ECMO studies meta-analysis was not possible.
Meta-regression, subgroup analysis, and evaluation of publication bias were not possible to perform due to low number of studies included for each indication.6 As majority of the studies, which reported survival, included only adult population, separate analysis for adult and pediatric populations was not possible.
Summary statistics were not calculated for two studies (case series and case study) which were selected primarily because of safety outcomes, as their primary focus was on reporting adverse events in selected patients but not in the cohort of patients.58,59 Meta-analysis of event rate using fixed-effect model indicated that mean occurrence of bleeding on device support was 28% (95% CI 23–32), thrombosis 7% (95% CI 5–11), hemolysis 3% (95% CI 1–6), neurological complications 7% (95% CI 4–11), infections 24% (95% CI 19–30), renal complications 28% (95% CI 22–36), and device failure 0.08% (95% CI 0.0–0.5). Device failure was reported only in two studies, whereas other 19 studies reported no device malfunction (three cases in total from 512 patients; naïvely pooled mean 0.58%).
Meta-analysis of event rate in adult compared with pediatric population showed that the mean occurrence of bleeding was 23% (95% CI 18–28%) versus 46% (95% CI 35–57%); thrombosis 4% (95% CI 1–9%) versus 22% (95% CI 14–31%); hemolysis 3% (95% CI 0–8%) versus 5% (95% CI 1–14%); neurological complications 6% (95% CI 3–11%) versus 12% (95% CI 6–20%); infections 24% (95% CI 18–30%) versus 26% (95% CI 16–39%); renal complications 22% (95% CI 15–31%) versus 39% (95% CI 27–53%); and device failure 0% versus 0% (95% CI 0–1%) consequently. Only incidence of bleeding and thrombosis differed statistically significant between adult and pediatric populations. Data for incidence of hemolysis, infection, and renal complications in pediatric population were available only in a single study.7
Evidence from 53 observational studies suggests that CentriMag is a versatile device for temporary mechanical circulatory support, which can be used as a VAD for all types of support (right-, left-, and biventricular) or as a part of the ECMO circuit. CentriMag provides good support in different patient groups. Average survival on VAD support varied from 61% in post-transplant graft rejection or failure indication to 83% in post-LVAD placement right ventricular failure indication. Prognosis in patients with cardiorespiratory failure remains good also beyond support with temporary VAD. Thus in the present meta-analysis 30-day survival was 66% in precardiotomy cardiogenic shock indication, 41% in postcardiac surgery cardiogenic shock indication, 54% in post-transplant graft rejection or failure indication, and 61% in post-LVAD placement right ventricular failure indication.
In the majority of publications, CentriMag was used as an urgent, immediate solution, since it can easily be utilized in both the VAD and the ECMO modes. It provides effective and inexpensive support until recovery of cardiac/respiratory function or until a decision about heart/lung transplantation or placement of a temporary, expensive ventricular assist has been made. The majority of patients present with multisystem organ failure and an often unclear neurological status, which may preclude immediate heart transplantation or implantation of a long-term VAD. Evidence suggests that immediate introduction of CentriMag support leads to recovery of heart function and weaning from device in a significant proportion of patients. In patients who are stable but not showing an improved cardiac function and in whom multisystem organ failure has been resolved, a decision about heart transplantation or placement of a permanent VAD can be made. By salvaging with CentriMag support, physicians have time to assess the dynamic of the clinical condition and make informed decisions about referring the patient to a heart transplant or permanent VAD implantation. Historical data shows, that without modern treatment, including temporary VADs, patients with cardiorespiratory shock have very poor prognosis. Analysis of incidence and mortality after cardiogenic shock, complicating acute myocardial infarction, in theUnited States showed that hospital survival in these patients ranged between 18.3% and 49.4% for the period of 1975–1999 years.60 In SHOCK prestudy Registry hospital survival for post-AMI cardiogenic shock patients was 37% for the period of 1992–1997 years.61 In our analysis, survival on support was 82.2% and 30-day survival was 66% in patients with pre-cardiotomy indication.
The important aspect of the CentriMag pump is the ability to work both in the VAD mode and as part of the ECMO circuit. Several studies report the versatility of adding an oxygenator to CentriMag VAD in situations of deterioration of respiratory function.37,46,49,56 This may allow effective and less complex support in clinical scenarios where the clinical condition is changing.
CentriMag is used in extremely ill patients in intensive care settings and the complication rate by definition is substantial. However, since these patients will most likely die without support, the complication rate may be considered acceptable. By definition, life-saving technologies used in patients with multiorgan failure due to cardiogenic shock are very invasive. The CentriMag pump is designed to decrease hemolysis and thrombus formation by employing magnetic levitation and bearing-less technology. This allows minimal friction and thermal energy generation during operation. One cohort study (Byrnes et al.17) found a nonsignificant trend toward a lower rate of ECMO circuit change with the CentriMag pump compared with the roller pump (Stockert-Shiley Sill) (15% and 50%, respectively). Unpublished study from the UK confirmed, that centrifugal (CentriMag) pump has significantly better safety profile in comparison with roller pump for ECMO support.7 The CentriMag system has only three reported pump failures in 21 studies of 512 patients. In our analysis, adult patients experienced less complications compared with pediatric population. Incidence of thrombosis and neurological complications in pediatric population was in general in line with data reported for Berlin Heart EXCOR (Berlin Heart AG, Berlin, Germany) in the recent study from the UK.62
Evidence is based predominantly on case series studies with three cohort studies and one case report. No prospective controlled trials were identified in the search. The majority of the studies collected data retrospectively, which may introduce bias in the evaluation of adverse events. Some publications were presented in the format of conference abstracts which limits the validity of results and extent to which they can be generalized. Some inconsistencies and variations in reporting were observed which limits the extent to which results may be generalized.
Despite the above-mentioned limitations, the clinical-evidence base has several significant strengths. The publications included in this study present a significant proportion of the worldwide experience with the CentriMag pump. The population eligible for VAD is limited to the most critically ill patients, who will most likely die without mechanical circulatory support. As it is difficult to conduct prospective randomized controlled trials in the area of urgent, rescuing ventricular assistance, evidence from a range of observational studies may be considered as appropriate. In most studies, hard and objectively measured endpoints (survival, weaning from support or bridging to transplant/long-term VAD) are reported which do not require special measurement and can easily be captured with retrospective analysis of data. In a majority of the included publications, the centers report their total CentriMag experience at the time for publication. This increases the extent to which results can be generalized. In the case of CentriMag support for acute cardiac graft failure, an audit of all adult heart transplants was reported.
Mean duration of support varied from 8.8 days for post-transplant graft failure indication to 25.0 days in precardiotomy indication. Range of support varied from 1 to 146 days. Although CentriMag is approved for 30-day support in the EU, many studies report its use beyond 30-day time frame, when required. Recently published study of CentriMag support at Royal Brompton and Harefield NHS Foundation Trust revealed that from 2003 154 CentriMag devices were used for support of which 46 (30%) devices were used for more the 30 days.63 Mean support time was 59 days (range 31–167 days) with major indication of refractory heart failure (85% of the patients). Overall, 74% patients were recovered or bridged, with a 1-year survival of 54%.
To the best of our knowledge, this study presents the first analysis of pooled efficacy and safety data for technology used for short-term bridge-to-decision or bridge-to-recovery indications in patients with cardiac and cardiorespiratory failure. Pooled estimates can be used as a benchmark for evaluation of efficacy and safety of other heart pumps in similar clinical situations and quality control of outcomes for short-term mechanical circulatory programs in real-world settings.
Results of comprehensive systematic literature review and meta-analysis showed that CentriMag is an effective technology for temporary support of patients with cardiac and cardiorespiratory failure. Evidence supports its use in different patient groups, including pre-cardiotomy, post-cardiac surgery cardiogenic shock, post-transplant graft failure or rejection, post-LVAD placement right ventricular failure.
The authors acknowledge Katherine Gottoli, PhD, Zeynep Colpan, MSc, Rongrong Zhang, MSc for editing support; Farhang Modaresi, MD, MDE, Irina Telegina, MD, PhD, Rongrong Zhang, MSc, Lian Zhang, PhD, Anchal Dutt, MD, Katarina Ericson, MSc for literature search and data retrieval, and Ana Turk, MSc for statistical support. The authors also thank three anonymous reviewers for valuable comments, which helped to improve the manuscript. The study was funded by Thoratec Corporation (Pleasanton, CA).
1. National Institute for Health and Clinical Excellence. Short-Term Circulatory Support with Left Ventricular Assist Devices as a Bridge to Cardiac Transplantation or Recovery. 2006 IPG177. London National Institute for Health and Care Excellence
2. ECMO. Extracorporeal Cardiopulmonary Support in Critical Care. 20054th ed:pp. 625
3. NHS England. Service Specification. . Ventricular Assist Devices (VADs) for adults as a bridge to heart transplantation or myocardial recovery. 2011
4. NHS England. Service Specification. . Ventricular Assist Devices (VADs) for children as a bridge to heart transplantation. 2011
5. Chuang-Stein C, Beltangady M. Reporting cumulative proportion of subjects with an adverse event based on data from multiple studies. Pharm Stat. 2011;10:3–7
6. Higgins JPT, Green SCochrane Handbook for Systematic Reviews of Interventions. 2011 Version 5.1.0 [updated March 2011]. The Cochrane Collaboration
7. Extracorporeal Membrane Oxygenation: An Evaluation of Current Treatment Approaches in the United Kingdom (Service Evaluation). 2013:pp. 43
8. Thomas HL, Dronavalli VB, Parameshwar J, Bonser RS, Banner NRAudit obotSGotUCT. . Incidence and outcome of Levitronix CentriMag support as rescue therapy for early cardiac allograft failure: A United Kingdom national study. Eur J Cardiothorac Surg. 2011;40:1348–1354
9. Hosmane S, Venkateswaran R, Salaie J, Williams S, Yonan N. Outcome of extracorporeal membrane oxygenation as short term mechanical support following heart transplantation: a single centre experience. Joint Annual Meeting of ACTA-SCTC. 2012 Manchester United Kingdom:pp. 139
10. De Robertis F, Birks EJ, Rogers P, Dreyfus G, Pepper JR, Khaghani A. Clinical performance with the Levitronix Centrimag short-term ventricular assist device. J Heart Lung Transplant. 2006;25:181–186
11. De Robertis F, Rogers P, Amrani M, et al. Bridge to decision using the Levitronix CentriMag short-term ventricular assist device. J Heart Lung Transplant. 2008;27:474–478
12. Akay MH, Gregoric ID, Radovancevic R, Cohn WE, Frazier OH. Timely use of a CentriMag heart assist device improves survival in postcardiotomy cardiogenic shock. J Card Surg. 2011;26:548–552
13. Aziz TA, Singh G, Popjes E, et al. Initial experience with CentriMag extracorporal membrane oxygenation for support of critically ill patients with refractory cardiogenic shock. J Heart Lung Transplant. 2010;29:66–71
14. Bhama JK, Kormos RL, Toyoda Y, Teuteberg JJ, McCurry KR, Siegenthaler MP. Clinical experience using the Levitronix CentriMag system for temporary right ventricular mechanical circulatory support. J Heart Lung Transplant. 2009;28:971–976
15. Bindoff C, Dean R, Bashford A, et al. Mobilization and physiotherapy of patients with Levitronix CentriMag short-term mechanical circulatory support device. J Heart Lung Transplant. 2009;28:S281
16. Bruschi G, Cannata A, Russo CF, et al. Single center experience with the Levitronix CentriMag circulation support system as short term cardiac assist in different clinical scenarios. J Heart Lung Transplant. 2008;27:S154–S155
17. Byrnes J, McKamie W, Swearingen C, et al. Hemolysis during cardiac extracorporeal membrane oxygenation: A case-control comparison of roller pumps and centrifugal pumps in a pediatric population. ASAIO J. 2011;57:456–461
18. Cassidy J, Haynes S, Kirk R, et al. Changing patterns of bridging to heart transplantation in children. J Heart Lung Transplant. 2009;28:249–254
19. Chen JM, Richmond ME, Charette K, et al. A decade of pediatric mechanical circulatory support before and after cardiac transplantation. J Thorac Cardiovasc Surg. 2012;143:344–351
20. Chung DA, Kizner L, Al-Deiri M, et al. Clinical utility of the Levitronix CentriMag in extracorporeal membrane oxygenation for severe cardiogenic shock. J Heart Lung Transplant. 2007;26:S87
21. Clough RE, Vallely MP, Henein MY, Pepper JR. Levitronix ventricular assist device as a bridge-to-recovery for post-cardiotomy cardiogenic shock. Int J Cardiol. 2009;134:408–409
22. den Uil CA, Maat AP, Lagrand WK, et al. Mechanical circulatory support devices improve tissue perfusion in patients with end-stage heart failure or cardiogenic shock. J Heart Lung Transplant. 2009;28:906–911
23. Di Bella I, Ramoni E, Da Col U, et al. Is lower limb venous drainage during peripheral extracorporeal membrane oxygenation necessary? ASAIO J. 2010;56:35–36
24. Favaloro RR, Bertolotti A, Diez M, et al. Adequate systemic perfusion maintained by a CentriMag during acute heart failure. Tex Heart Inst J. 2008;35:334–339
25. Garcia JP, Kon ZN, Evans C, Wu Z, IA M, cCormick B, Griffith BP. Ambulatory veno-venous extracorporeal membrane oxygenation: Innovation and pitfalls. J Thorac Cardiovasc Surg. 2011;142:755–761
26. Gašparović H, Petričević M, Ivančan V, Miličić C, Biočina B. Initial clinical results with the Levitronix CentriMag Mechanical Assist Device at the University Hospital Rebro Zagreb. Rad Med Fak Zagrebu. 2011;36:47–53
27. Haj-Yahia S, Birks EJ, Amrani M, et al. Bridging patients after salvage from bridge to decision directly to transplant by means of prolonged support with the CentriMag short-term centrifugal pump. J Thorac Cardiovasc Surg. 2009;138:227–230
28. Horváth V, Němec P, Ondrášek J, et al. Short-term mechanical support with the Levitronix CentriMag centrifugal pump. Cor Vasa. 2011;53:144–147
29. John R, Liao K, Lietz K, et al. Experience with the Levitronix CentriMag circulatory support system as a bridge to decision in patients with refractory acute cardiogenic shock and multisystem organ failure. J Thorac Cardiovasc Surg. 2007;134:351–358
30. John R, Long JW, Massey HT, et al. Outcomes of a multicenter trial of the Levitronix CentriMag ventricular assist system for short-term circulatory support. J Thorac Cardiovasc Surg. 2011;141:932–939
31. Khan N, Al-alouo M, Shad DL. Early experience with the Levitronix CentriMag device for extra corporeal membrane oxygenation following lung transplantation. Eur J Cardiothorac Surg. 2008;34:1262–1264
32. Kouretas PC, Kaza AK, Burch PT, et al. Experience with the Levitronix CentriMag in the pediatric population as a bridge to decision and recovery. Artif Organs. 2009;33:1002–1004
33. Loforte A, Montalto A, Ranocchi F, et al. Temporary mechanical circulatory support for acute cardiogenic shock. Eur J Heart Fail. 2010;9:S193–S194
34. Loforte A, Potapov E, Krabatsch T, et al. Levitronix CentriMag to Berlin Heart Excor: A “bridge to bridge” solution in refractory cardiogenic shock. ASAIO J. 2009;55:465–468
35. Loforte A, Montalto A, Ranocchi F, et al. Levitronix CentriMag third-generation magnetically levitated continuous flow pump as bridge to solution. ASAIO J. 2011;57:247–253
36. Loforte A, Montalto A, Lilla Della Monica P, Musumeci F. Simultaneous temporary CentriMag right ventricular assist device placement in HeartMate II left ventricular assist system recipients at high risk of right ventricular failure. Interact Cardiovasc Thorac Surg. 2010;10:847–850
37. Maat AP, van Thiel RJ, Dalinghaus M, Bogers AJ. Connecting the Centrimag Levitronix pump to Berlin Heart Excor cannulae; a new approach to bridge to bridge. J Heart Lung Transplant. 2008;27:112–115
38. Marquez TT, D’Cunha J, John R, Liao K, Joyce L. Mechanical support for acute right ventricular failure: Evolving surgical paradigms. J Thorac Cardiovasc Surg. 2009;137:e39–e40
39. McCormick AJ, Reid BB, Budge D, et al. Versatility and patient outcomes with the levitronix centrimag temporary ventricular assist device. J Heart Lung Transplant. 2010;29:S100
40. Meyer AL, Strueber M, Tomaszek S, et al. Temporary cardiac support with a mini-circuit system consisting of a centrifugal pump and a membrane ventilator. Interact Cardiovasc Thorac Surg. 2009;9:780–783
41. Morgan JA, Naseem TM, Cheema FH, et al. Improvement in survival with implantation of levitronix centrimag biventricular circulatory support in patients with acute st-elevation myocardial infarction (STEMI) and refractory cardiogenic shock. J Heart Lung Transplant. 2009;28:S143
42. Nelson KM, Marks JD, Eidson M, et al. Initial pilot study of the Levitronix CentriMag VAS for RVAD support following LVAD implementation. ASAIO J. 2006;52:36A
43. Netuka I, Malý J, Szarszoi O, et al. [Technique of implantation and experience with temporary mechanical cardiac support in right ventricular failure]. Rozhl Chir. 2011;90:88–94
44. Pawlak S, Sliwka J, Przybylski R, et al. Peirwsze doswiadczenia w kiniczynm zastosowaniu system wsopmagania serca pompa rotacynja Levitronix. (Early experience in clinical use of mechanical ventricular assist Levitronix device). Kardiochirugia I Torakochirugia i Polska. 2009;6:171–175
45. Reckers J, Asfour B, Fink C Goodbye Hemolysis! Experience with Levitronix CentriMag in 33 Newborns, Infants and Children. 2008 54th Annual Conference of ASAIO. San Francisco, United States
46. Russo CF, Cannata A, Lanfranconi M, et al. Veno-arterial extracorporeal membrane oxygenation using Levitronix centrifugal pump as bridge to decision for refractory cardiogenic shock. J Thorac Cardiovasc Surg. 2010;140:1416–1421
47. Santise G, Petrou M, Pepper JR, Dreyfus G, Khaghani A, Birks EJ. Levitronix as a short-term salvage treatment for primary graft failure after heart transplantation. J Heart Lung Transplant. 2006;25:495–498
48. Shuhaiber JH, Jenkins D, Berman M, et al. The Papworth experience with the Levitronix CentriMag ventricular assist device. J Heart Lung Transplant. 2008;27:158–64
49. Singh RK, Addonizio LJ, Richmond M, Vincent J, Torres A, Williams M. A novel approach to management of acute rejection with percutaneous ventricular assist device insertion in two adolescent heart transplant patients. J Card Fail. 2009;15:S55
50. Soleimani B, Brehm C, Wallace S, et al. Application of new generation rotary pumps and oxygenators for veno-arterial extracorporeal membrane oxygenation (VA-ECMO) for refractory cardiogenic shock (RCS). J Heart Lung Transplant. 2011;30:S211
51. Stepanenko A, Pappalardo F, Scandroglio AM, Potapov EV, Krabatsch T, Hetzer R. Anticoagulation management during CentriMag right ventricular assist device support after heartmate II implantation. Heart Surg Forum. 2010;13:S113
52. Takayama H, Chen JM, Jorde UP, Naka Y. Implantation technique of the CentriMag biventricular assist device allowing ambulatory rehabilitation. Interact Cardiovasc Thorac Surg. 2011;12:110–111
53. Takayama H, Naka Y, Kodali SK, et al. A novel approach to percutaneous right-ventricular mechanical support. Eur J Cardiothorac Surg. 2012;41:423–426
54. Westaby S, Balacumaraswami L, Evans BJ, et al. Elective transfer from cardiopulmonary bypass to centrifugal blood pump support in very high-risk cardiac surgery. J Thorac Cardiovasc Surg. 2007;133:577–578
55. Worku B, Naka Y PS, Cheema FH, et al. Predictors of mortality after short-term ventricular assist device placement. Ann Thorac Surg. 2011;92:1608–1612
56. Yang JA, Takayama H, Kim H, Cohen SA, Naka Y. Feasibility of BiVAD support with membrane oxygenation. J Heart Lung Transplant. 2010;29:S181–S182
57. Zych B, Popov AF, Barsan A, et al. Treatment of refractory right heart failure after implantation of a left ventricular assist device. Is the levitronix centrimag right heart support a solution? Heart. 2011;97:A49
58. Velik-Salchner C, Hoermann C, Hoefer D, Margreiter J, Mair P. Thromboembolic complications during weaning from right ventricular assist device support. Anesth Analg. 2009;109:354–357
59. Sims DB, Takayama H, Uriel N, Gillam LD, Naka Y, Jorde UP. Ventricular assist device-associated thrombus. Circulation. 2011;124:e197–e198
60. Goldberg RJ, Spencer FA, Gore JM, Lessard D, Yarzebski J. Thirty-year trends (1975 to 2005) in the magnitude of, management of, and hospital death rates associated with cardiogenic shock in patients with acute myocardial infarction: A population-based perspective. Circulation. 2009;119:1211–1219
61. Carnendran L, Abboud R, Sleeper LA, et al. Trends in cardiogenic shock: report from the SHOCK Study. The SHould we emergently revascularize Occluded Coronaries for cardiogenic shocK? Eur Heart J. 2001;22:472–478
62. Cassidy J, Dominguez T, Haynes S, et al. A longer waiting game: bridging children to heart transplant with the Berlin Heart EXCOR device—The United Kingdom experience. J Heart Lung Transplant. 2013;32:1101–1106
63. Mohite PN, Zych B, Popov AF, et al. CentriMag short-term ventricular assist as a bridge to solution in patients with advanced heart failure: Use beyond 30 days. Eur J Cardiothorac Surg. 2013;44:e310–e315
ventricular assist device; extracorporeal membrane oxygenation; mechanical circulatory support; cardiorespiratory failure; systematic literature review