Secondary Logo

Journal Logo

THORACIC TRANSPLANTATION: Edited by Andreas Zuckermann

New role of ventricular assist devices as bridge to transplantation

European perspective

Reineke, David C.a; Mohacsi, Paul J.b

Author Information
Current Opinion in Organ Transplantation: June 2017 - Volume 22 - Issue 3 - p 225-230
doi: 10.1097/MOT.0000000000000412
  • Open



Mechanical circulatory support (MCS) has become a pre-dominant factor in the treatment of end-stage heart failure. Especially technical advances in the field of left ventricular assist devices (LVADs) offer solutions that are not only about survival but offer quality of life at the cost of acceptable morbidity on the waiting list in times of donor scarcity. We will focus on the new role of bridging a patient to transplant and try to highlight differences in approaches between Europe and the United States. We will discuss the burdens of such a therapy, not only on the patients but also on relatives. Whether LVADs will replace organ heart transplantation (HTx) in the future is uncertain. Today, HTx is the only reasonable option for transplantable patients.

Box 1:
no caption available


Two main factors are responsible for organ scarcity in transplantation medicine. There is a growing lack of donors especially in the European countries because of scepticism towards the organ allocation system, e.g. scandals in Germany due to irregularities, and an ever-growing demand of organs because of patients benefiting from improving medical systems (Fig. 1). This is especially true in cardiovascular medicine. While in the last 30 years coronary death was halved by medical progress, heart failure has almost tripled with more patients reaching end-stage heart failure and requiring transplantation [1,2].

Imbalance of demand and supply: waiting list is increasingly larger than the number of heart transplants. Reused with permission from —Heart waiting list and transplants, by year-chart. Source:

Although orthotopic HTx is up to date, the only curative option in the treatment of end-stage heart failure, the great imbalance between donors and patients listed for HTx consequently results in patients being increasingly treated with mechanical support devices for bridge to transplant (BTT) [3].


The concept of bridging a patient to transplant has changed in the last years from simply preventing a patient dying on the waiting list to making him/her eligible for receiving an organ [bridge to candidacy (BTC)]. The possibility to offer patients these options can mostly be put back to the technical advances moving from first-generation pulsatile flow LVADs to second- and third-generation continuous flow (CF) devices.


The change from pulsatile to CF devices has opened the door to very differentiated treatment concepts. Miniaturized third-generation ‘hydrodynamic’ (HVAD HeartWare/Medtronic) and fully ‘magnetically’ (SJM/Thoratec, HeartMate 3) levitated flow technology has enabled minimal invasive implants placed intrapericardially and via left anterior thoracotomy protecting the right ventricle and making reoperations easier [4].

Newest third-generation devices such as SJM‘s HeartMate 3 combine CF and an artificial pulse assisting with pump washing in order to reduce thrombus related adverse events. This concept of a ‘programmed pulsatility’ might in the long-term reduce gastric bleeding, aortic valve insufficiency and peripheral vasoplegia. These factors seem to be closely related to a pulseless life and increase morbidity especially in long-term LVAD support [5▪].

Second and third-generation devices dominate the market since 2008 with superior outcomes to their predecessors with survival of 90, 84 and 79% at 6, 12 and 24 months respectively [6]. Well-designed studies monitor long-term efficacy of two key devices. ENDURANCE (HVAD) and MOMENTUM 3 (HeartMate 3) will hopefully be able to give a sound ideas of state of the art device therapy and further improve their quality adjusted life year values [7▪▪,8▪▪].


Because of these incredible advances in device manufacturing, today bridging a patient to transplantation is about offering tailor made solutions for defined situations. To preserve end-organ function, LVADs may even be implanted electively when a long wait is foreseeable, especially in patients with blood type 0 [9▪]. The same goes for patients who are stable, will need an organ at some stage, but are not yet eligible for transplant. A good example for this strategy is cardiorenal syndrome, pulmonary hypertension (PH) or a recently treated malignoma.

Transplantation in patients with presumably ‘fixed’ PH is contraindicated because of the high rate of right heart failure post-transplantation. It was demonstrated, that LVAD therapy is able to decrease elevated transpulmonary gradients or pulmonary vascular resistance and successfully overcome this contraindication for cardiac transplantation. Zimpfer et al. were able to show a relevant decrease in PH during a six-week period of support. In view of the high risk of donor heart failure in patients with ‘fixed’ PH, the alternative of prior LVAD support and subsequent orthotropic HTx has proven to be a good concept [10].

This concept is theoretically also applicable to tumour illnesses in the form of bridge to tumour-free status. For patients with chemotherapy-induced DCM technical advances allow device placement and achievement of tumour-free intervals over a two to five-year interval prior to HTx [11,12].


Because of differences in donor availability and allocation process the relationship and approach towards implanting VADs as BTT is different in the United States and Europe. Although 1-year survival has considerably improved, current UNOS policy is still based on the experience with first-generation assist devices, which in general were able to only provide reliable support for 1 year. LVAD patients are automatically given 1B status and are allowed a 30-day 1A period to avoid device complications. This is of course questionable in light of near 90% survival in the current BTT patients [13]. In Europe, on the other hand, stable heart failure patients on device support are not prioritized.

This has led to a diametric development in the lives of BTT patients on both continents. While the concept of BTT has more than halved the rate of patients dying on the waiting list in Europe and America [14] the fate of these patients is completely different. As reported in the 7th INTERMACS annual report, in America about 60% of donor hearts now go to patients with LVADs on the waiting list due to early automatic prioritization [15▪▪]. This is not the case in Europe. In 2015, Germany transplanted 82% of the patients in high urgency category. As only device complications are prioritized in Germany, waiting lists of patients on LVAD support are on the increase [16]. So in reality, in Germany, the decision to implant an LVAD very nearly equals the concept of destination therapy (DT).


Although VAD patients have a substantial improvement in activities and quality of life, they do not reach levels generally achieved after HTx. Despite of LVAD support, 12% of patients die on the waiting list. After 2 years, 30% have become ineligible for an HTx because of disabling stroke from embolic or intracranial bleeding events, sepsis, progressive kidney or liver dysfunction. Once any of these conditions become severe enough to compromise outcome of HTx, these patients find themself on an unidentified pathway they did not consent to [9▪,17].

While at first glance abbreviations like BTT or DT seem to have a semantic character, the endorsement to one of those acronyms has in reality forced clinicians into the practice of stating their intention of therapy and strategy at the time of implant. In order to avoid these polarizing decisions a ‘no clear intent’ strategy in the form of a ‘BTC’ has become a third option.

Implant strategies change all the time or as Fang et al. nicely pointed out in an editorial on an article on VAD strategies ‘that an inherent limitation of such an approach is the attempt to predict the future’. In his study, Teuteberg et al. focus on the practice of formulating intent strategy at the time of LVAD implant. They show that intended strategies change over time, limiting the usefulness of these plans. In this study, among 2816 primary LVAD patients, 1060 patients were designated BTT candidates. At 2 years, 43.5% where no longer listed for transplant [17,18]. More realistic triage to VAD as lifetime (destination) therapy, rather than to a long transplant waiting list would encourage patients and families to more fully embrace and adapt their lives to enjoy maximal benefit from MCS [9▪].


Psychological issues and the effect on surrounding relatives

Compared to palliative treatment strategies [19,20], MCS is an alternative, but expensive treatment option for end-stage heart disease. The incidence of pre-morbid and post-surgical psychiatric disorders, the use of psychotropic drugs, as well as neurologic events must be taken into account when evaluating the indication for an LVAD [21,22] as psychiatric burden influences compliance and overall outcome. After discharge of a VAD patient, caregivers are additionally placed under significant pressure, which changes over the span of the VAD experience. Different coping mechanisms are used to deal with the initial shock and significant burden [23]. However, partner support seems to be one of the most significant psychosocial variables that can influence clinical success after HTx [24]. Since most of the LVAD patients are waiting for a HTx, the following psychological predictors [24] might also be applied for VAD candidates: empathy, partner support (affective involvement), few demands for emotional communication (affective expression), self-control, stress resistance, emotional stability, high frustration tolerance, low aggression level and younger age. Interestingly, BTT strategy does not lead to post-traumatic stress disorder in patients but may do in their spouses in the long run [25,26].

Redo operation

Several reports have focused on post-transplant survival in patients who were previously treated with a device. Multi-variate analysis of registry data suggested that mechanical support is a predictive factor for poor transplant survival [27]. More recent reports focusing exclusively on long-term LVAD use as BTT has refuted these observations [28,29].

For a centre having great experience with all kinds of redo-surgery including transplantation after LVAD, it is not understandable why results should not suffer from a redo situation. Increased bleeding with post-operative mass transfusions surely influence the acute function of the right ventricle and may influence the immune system with possible rejections in the future. Current research shows that open-heart surgery for the placement of VADs in heart failure patients may be associated with the development of a systemic inflammatory response syndrome because of increased oxidative stress leading to clinical complications and organ dysfunction. VADs are thought to induce high levels of inflammation as a result of exposure to non-physiological flow conditions or artificial surfaces. In daily life we witness that capillary leak syndromes after VAD-transplantations prolong hemodynamic stabilization and post-operative course [30,31▪,32▪]. Should complicated LVAD patients comprise the majority of transplant patients in the future, it will only be a matter of time, when post-transplant survival will suffer.

Neurologic dysfunction

Recently reported event rates vary between 9.8 and 40% (0.21 thromboembolic strikes per year and 0.19 haemorrhagic strokes per year). The ReVOLVE trial revealed neurological dysfunction accounting for death in 4.3% of patients after a mean time of 145 days within a range of 1–730 days. Stroke of any kind occurred in 8% of patients during the same period. The 7th INTERMACS report reported 1.17 neurologic events per 100 patient months for patients implanted between 2008 and 2011, and 1.71 events for patients implanted between 2012 and 2014. INTERMACS levels did not influence neurological events significantly.

Comparing third- and second-generation devices in view of neurologic outcomes, complication rates were reported as 19% for 0.44 median years (HeartWare) and 16% for 0.95 median years (HeartMate II) of follow-up [13,15▪▪,32▪,33–36].

Gastrointestinal bleeding

Gastrointestinal bleeding (GIB) is the most common reason for readmission after implantation of MCS. Although direct comparison in literature is difficult because of differences in definitions and reporting, similar rates of GIB are documented throughout current literature. ReVOLVE and Slaughter et al. report comparable event rates per patient year of 14.8, 12.7 and 26%. These results are also in line with the 7th INTERMACS report. A recent meta-analysis by Draper et al. which included 17 studies and 1697 patients reported a pooled incidence rate of GIB in patients on LVAD of 23%. The prevalence of GIB was increased in LVAD patients, primarily because of proximal GI angiodysplastic lesions. Risk factors included older age and elevated creatinine [13,36–38].


Infections are a frequent complication. They can occur because of exposure to invasive therapies, prolonged hospitalizations and of course, because of the percutaneous lead. Causes for readmission are mainly VAD specific complications in the form of driveline or even hardware infections. Antibiotic and antifungal therapy in addition to surgical source control is crucial. Every effort must be made to clear the infection prior to HTx with its immunosuppressive therapy.

In the ADVANCE BTT trial, which was aimed at the approval of the HVAD HeartWare as BTT, driveline infections and sepsis, occurred in 12 and 11% of patients, respectively. This is numerically lower than in second-generation device pivotal trials. In a pooled multi-centre analysis of Stulak et al. 734 patients with an LVAD where reviewed for their adverse events. Cumulative risk of percutaneous driveline infection at 1, 3 and 5 years was 7, 20 and 29% respectively. Cumulative risk of any infection for the entire cohort was 17, 33 and 45%, at 1, 3 and 5 years [39,40▪▪].

Pump thrombosis

Despite an overall reduction of adverse events over the last years, the INTERMACS database reported a six-fold increase in the rates of pump thrombosis in Heart Mate II patients between 2011 and 2012. HeartWare investigators also noticed a higher incidence of thrombosis in their device (0.063–0.08 events/patient year). An investigation found that most pump thromboses occurred because of sub-therapeutic warfarin anticoagulation and taking low-dose aspirin (i.e., 81 mg) or no antiplatelet therapy at all. After additional technical modifications in the region of the inflow cannula and stricter management of anticoagulation, device exchange because of pump thrombosis fell by greater than 50%. Stulak et al. reported a cumulative risk of pump thrombus for his entire cohort of 14, 24 and 25%, at 1, 3 and 5 years. In accordance with the above cited data, pre-2011 data showed a high overall incidence of thrombosis of 30% and a much lower rate of 7.6% after change of strategy [13,41▪▪,42▪▪].


The European Registry for Patients with Mechanical Circulatory Support (EUROMACS) was founded in 2009 to focus on European data. EUROMACS is the only existing European-based mechanical support registry for all devices implanted in children and adults. Other registries like the American counterpart INTERMACS (Interagency registry on mechanically assisted circulatory support) only register Food and Drug Administration (FDA)–approved devices and no paediatric patients. When the first annual EUROMACS report was presented at the Annual Meeting of the European Association of Cardio-Thoracic Surgery authors emphasized that no big differences could be seen between the continents. In our view, there are noteworthy differences to mention. While in EUROMACS only 16% patients are categorized as destination patients it is nearly half of all implants in INTERMACS. What strikes the attentive reader of both reports is also the outcome. While the actuarial survival rate of CF LVADs in the INTERMACS cohort after 12 and 24 months is 80 and 70%, survival in EUROMACS is considerably lower with 72.5% after one year and 62.8 at 2 years. Equally interesting is the comparison of causes of death. While in EUROMACS, the main cause of death is infection, sepsis and multi-organ failure, in INTERMACS its neurologic events. Of course this is in some way like comparing apples and pears but once reporting mechanisms in both registries are fully deciphered it will be interesting to see whether existing differences influence implantation strategies in both Europe and America [13,43▪▪]. These differences should also be taken into account in amalgamated data, such as the IMACS registry (ISHLT mechanically assisted circulatory support registry) [44].


The VAD technology improved from generation to generation remarkably leading to improved survival and seemingly low morbidity, at the same time. However, from the European point of view, updated analysis of EUROMACS retrieves a different picture with respect to mortality and morbidity. In fact, we do have to accept in daily life the burden of serious adverse events of about 65% during the first year of bridging, which reinforces the incredible value of HTx. We are sometimes faced by the statement that the concept of HTx is futureless, which seems to be for someone who treats and compares both patients in daily practice questionable. Up to now, LVAD therapy remains a bridge to a better future, which means a bridge to technical innovations or to overcome the dramatic lack of donors in Europe.


We acknowledge all EUROMACS contributing members.

Financial support and sponsorship

This publication was supported by the Katharina Huber-Steiner Foundation.

Conflicts of interest

P.J.M. received honoraria and travel grants from Medtronic (HeartWare). He is also founding member and currently vice-chairman of EUROMACS.


Papers of particular interest, published within the annual period of review, have been highlighted as:

  • ▪ of special interest
  • ▪▪ of outstanding interest


1. Hsich E. Matching the market for transplantation. Circ Heart Fail 2016; 9:e002679.
2. United Network of Organ Sharing public data reports. Accessed 1 March 2015.
3. Lund LH, Edwards LB, Kucheryavaya AY, et al. International Society for Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: Thirtieth Official Adult Heart Transplant Report-2013; focus theme: age. J Heart Lung Transplant 2013; 32:951–964.
4. Reineke DC, Carrel TP. Less invasive left ventricular assist device implantation-a match changer!. J Thorac Dis 2015; 7:783–786.
5▪. Schmitto JD, Zimpfer D, Fiane AE, et al. Long-term support of patients receiving a left ventricular assist device for advanced heart failure: a follow-up analysis of the Registry to Evaluate the HeartWare Left Ventricular Assist System. Eur J Cardiothorac Surg 2016; 50:834–838.

Valuable long-term data on the treatment with 3rd generation LVAD.

6. Strueber M, O’Driscoll G, Jansz P, et al. Multicenter evaluation of an intrapericardial left ventricular assist system. J Am Coll Cardiol 2011; 57:1375–1382.
7▪▪. Rogers JG, Pagani FD, Tatooles AJ, et al. Intra pericardial left ventricular assist device for advanced heart failure. (Funded by HeartWare; ENDURANCE Clinical Trials; gov number, NCT01166347). N Engl J Med 2017; 376:451–460.

Well designed study monitoring long-term efficacy of 3rd generation LVAD.

8▪▪. Mehra MR, Naka Y, Uriel N, et al. A fully magnetically levitated circulatory pump for advanced heart failure (MOMENTUM 3 Clinical Trials; gov. number, NCT022247555). N Engl J Med 2017; 376:440–450.

Well designed study monitoring long-term efficacy of 3rd generation LVAD.

9▪. Stevenson L. Crisis awaiting heart transplantation: sinking the lifeboat. JAMA Intern Med 2015; 175:1406–1409.

Very precise portrayal of the crisis awaiting heart transplant.

10. Zimpfer D, Zrunek P, Roethy W, et al. Left ventricular assist devices decrease fixed pulmonary hypertension in cardiac transplant candidates. J Thorac Cardiovasc Surg 2007; 133:689–695.
11. Miller J, Lancaster T, Eghtesady P. Current approaches to device implantation in pediatric and congenital heart disease patients. Expert Rev Cardiovasc Ther 2015; 13:417–427.
12. Sigurdardottir V, Bjortuft O, Eiskjær H, et al. Long-term follow-up of lung and heart transplant recipients with pretransplant malignancies. J Heart Lung Transplant 2012; 31:1276–1280.
13. Uriel N, Jorde U, Woo Pak S, et al. Impact of long term left ventricular assist device therapy on donor allocation in cardiac transplantation. J Heart Lung Transplant 2013; 32:188–195.
14. Meyer DM, Rogers JG, Edwards LB, et al. The future direction of the adult heart allocation system in the United States. Am J Transplant 2015; 15:44–54.
15▪▪. Kirklin JK, Naftel DC, Pagani FD, et al. Seventh INTERMACS annual report: 15,000 patients and counting. J Heart Lung Transpl 2015; 34:1495–1504.
16. Eurotransplant/annual report 2015 (
17. Teuteberg JJ, Stewart GC, Jessup M, et al. Implant strategies change over time and impact outcomes: insights from the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support). J Am Coll Cardiol HF 2013; 1:369–378.
18. Fang JC, Stehlik J. Moving beyond ‘bridges’. JACC Heart Fail 2013; 1:379–381.
19. Jaarsma T, Beattie M, Ryder M, et al. Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Associastion of the European Society of Cardiology. Eur J Heart Fail 2009; 11:433–443.
20. Goodlin S, Hauptman P, Arnold R, et al. Consensus statement: palliative and supportive care in advanced heart failure. J Card Fail 2004; 10:200–209.
21. Petrucci R, Kushon D, Inkles R, et al. Cardiac ventricular support: considerations for psychiatry. Psychosomatics 1999; 40:298–303.
22. Levenson L, Olbrisch M. Psychiatric aspects of heart transplantation. Psychosomatics 1993; 34:114–123.
23. Kaan A, Young Q, Cockell S, Mackay M. Emotional experiences of caregivers of patients discharged on ventricular assist device (EECVAD). J Heart Lung Transplant 2009; 28:S218–S219.
24. Bunzel B, Wollenek G. Heart transplantation: are there psychosocial predictors for clinical success of surgery? Thorac Cardiovasc Surg 1994; 42:103–107.
25. Bunzel B, Laederach-Hofmann K, Wiesenthaler G, et al. Mechanical circulatory support as a bridge to heart transplantation: what remains? Long-term emotional sequelae in patients. J Heart Lung Transplant 2007; 26:384–389.
26. Bunzel B, Laederach-Hofmann K, Wiesenthaler G, et al. Posttraumatic stress disorder after implantation of a mechanical assist device followed by heart transplantation: evaluation of patients and partners. Transplant Proc 2005; 37:1365–1368.
27. Patolla V, Patten R, Denofrio D, et al. The effect of ventricular assist devices on post transplant mortality in analysis of the United Network for organ sharing thoracic registry. J Am Coll Cardiol 2009; 5:264–271.
28. Osaki S, Edwards N, Johnson M, et al. Improved survival after heart transplantation in patients with bridge to transplant in the recent era: a 17 year single center experience. J Heart Lung Transplant 2009; 28:591–597.
29. Russo M, Hong K, Davies R, et al. Posttransplant survival is not diminished in heart transplant recipients bridged with implantable left ventricular assist devices. J Thorac Cardiovasc Surg 2009; 138:1425–1432.
30. Mondal NK, Sorensen E, Feller E, et al. Systemic inflammatory response syndrome (SIRS) after contentious-flow left ventricular assist device implantation and change in platelet mitochondrial membrane potential. J Card Fail 2015; 21:564–571.
31▪. Mondal NK, Sorensen EN, Pham SM, et al. Systemic inflammatory response syndrome in end-stage heart failure patients following continuous-flow left ventricular assist device implantation: differences in plasma redox status and leukocyte activation. Artif Organs 2016; 40:434–443.

Influence of the LVAD on inflammation and immunologic response.

32▪. Mondal NK, Sobieski MA, Pham SM, et al. Infection, oxidative stress and changes in circulating regulatory T cells of heart failure patients supported by continuous-flow ventricular assist devices. ASAIO 2017; 63:128–133.

Influence of the LVAD on inflammation and immunologic response

33. Whitson BA, Eckman P, Kamdar F, et al. Hemolysis, pump thrombus and neurologic events in continuous-flow left ventricular assist device recipients. Ann Thorac Surg 2014; 97:2097–2103.
34. Bashir J, Legare JF, Freed DH, et al. Multicentre Canadian experience with the HeartWare ventricular assist device: concerns about adverse neurological outcomes. Can J Cardiol 2014; 30:1662–1667.
35. Coffin ST, Haglund NA, Davis ME, et al. Adverse neurologic events in patients bridged with long-term mechanical circulatory support: a device-specific comparative analysis. J Heart Lung Transplant 2015; 34:1578–1585.
36. Strueber M, Larbalestier R, Jansz P, et al. Results of the postmarket Registry to Evaluate the HeartWare Left VentricularAssist System (ReVOLVE). J Heart Lung Transplant 2014; 33:486–491.
37. Draper KV, Huang RJ, Gerson LB. GI bleeding in patients with continuous flow left ventricular assist devices: a systematic review and meta-analysis. Gastrointest Endosc 2014; 80:435–446.
38. Slaughter MS, Pagani FD, McGee EC, et al. Use of the HeartWare® ventricular assist system for bridge to transplant: combined results of the ADVANCE and CAP Trial. J Heart Lung Transplant 2013; 32:675–683.
39. John R, Aaronson KD, Pae WE, et al. Drive-line infections and sepsis in patients receiving the HVAD system as a left ventricular assist device. HeartWare Bridge to Transplant ADVANCE Trial Investigators. J Heart Lung Transplant 2014; 33:1066–1073.
40▪▪. Stulak JM, Davis ME, Haglund N, et al. Adverse events in contemporary continuous-flow left ventricular assist devices: a multiinstitutional comparison shows significant differences. J Thorac Cardiovasc Surg 2016; 15:177–189.

Well designed multicenter study on contemporary LVADs.

41▪▪. Stulak JM, Dunlay SM, Sharma S, et al. Treatment of device thrombus in the HeartWare HVAD: success and outcomes depend significantly on the initial treatment strategy. J Heart Lung Transplant 2015; 34:1535–1541.

Initial medical therapy is associated with low success.

42▪▪. Kirklin JK, Naftel DC, Pagani FD, et al. Pump thrombosis in the Thoratec HeartMate II device: an update analysis of the INTERMACS Registry. J Heart Lung Transplant 2015; 34:1515–1526.

Analysis of HMII pump thrombosis.

43▪▪. de By TM, Mohacsi P, Gummert J, et al. on behalf of the EUROMACS members. The European Registry for Patients with Mechanical Circulatory Support (EUROMACS): first annual report. Eur J Cardiothorac Surg 2015; 47:770–776.
44. Kirklin JK, Cantor R, Mohacsi P, et al. First annual IMACS report: a global international society for Heart and Lung Transplantation registry for mechanical circulatory support. J Heart Lung Transplant 2016; 35:407–412.

bridge-to-transplantation; heart transplantation; ventricular assist device

Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.