This policy was created in 2008 and regularly updated with searches of the MEDLINE database. The most recent literature search was performed for the period from July 2011 through July 2012. The literature review focuses on 3 types of devices: 1) left ventricular assist devices (LVAD), 2) total artificial hearts (TAH), and 3) percutaneous ventricular assist devices (pVAD). The literature review addresses short-term use of the devices as a bridge to recovery or transplantation. The LVADs and TAHs are also evaluated as longer-term destination therapy for patients who are not transplant candidates. Following is a summary of the key literature to date.
Left ventricular assist devices (LVADs)
LVADs as Bridge to Recovery: Post-cardiotomy Setting
Five studies of the Centrimag Right Ventricular Assist Device (RVADs) included between 12 and 32 patients, the majority of whom received biventricular devices. (2-4) Indications (and numbers of patients) in these 5 studies were: support for post-cardiotomy cardiogenic shock (bridge to recovery, n=53), bridge to long-term device implantation (n=9), treatment of right heart failure in patients who previously received left ventricular assist devices (LVADs) (n=15), bridge to later decision when neurologic status is clarified (n=16), and acute donor graft failure (n=6). The mean time on mechanical circulatory support ranged from 9.4 days to 46.9 days. The 30-day mortality rates were between 17% and 63%. The proportion of patients discharged from the hospital was between 30% and 83%. Major complications included bleeding requiring reoperation, sepsis, and stroke. No device failures were observed in these studies.
LVADs as Bridge to Transplant
A 1996 TEC Assessment concluded that left ventricular assist devices (LVADs) can provide an effective bridge to transplantation. (5) Goldstein and colleagues published a more recent review. (6) It should be recognized that LVADs do not change the number of patients undergoing heart transplantation due to the fixed number of donor hearts. However, the VAD will categorize its recipient as a high-priority heart transplant candidate.
Published studies continue to report that the use of a VAD does not compromise the success of a subsequent heart transplant and, in fact, may improve post-transplant survival, thus improving the use of donor hearts. (7-10) Currently available implantable LVADs consist of pulsatile devices that require stiff power vent lines that perforate the skin and implantable pump chambers, as well as non-pulsatile axial flow systems of smaller size and lower noise levels. (11)
In 5 reports, with samples ranging from 32 to 279 patients, most participants received the continuous-flow device as a bridge to transplantation. (12-16) Survival rates at 6 months were between 67% and 87%, and between 50% and 80% at 1 year. These rates are similar to those observed in a recent report of a federal circulatory support device registry. (17) A study by Patel and colleagues compared HeartMate I and HeartMate II recipients at a single center, finding the same 1-year survival and similar rates of subsequent development of right heart failure. (15) Serious adverse events occurring after HeartMate II-implantation include bleeding episodes requiring reoperation, stroke, infection, and device failure.
A systematic review published in 2012 examined the evidence on the effect of LVADs on post-transplant outcomes. (18) This review included 31 observational studies that compared outcomes of transplant in patients who did and did not have pre-transplant LVAD. Survival at one year was more likely in patients who had LVAD treatment, but this benefit was confined to patients who received an intra-corporeal device (relative risk [RR]: 1.8, 95% confidence interval [CI]: 1.53-2.13). For patients treated with an extracorporeal device, the likelihood of survival was not different from patients who were not treated with an LVAD (RR: 1.08, 95% CI: 0.95-1.22). There was no difference in the risk of rejection between patients who did and did not receive LVAD treatment.
There is a U.S. Food and Drug Administration (FDA)-approved device, via the Humanitarian Device Exemption (HDE) process, available for use as a bridge to cardiac transplant in children. This HDE approval was based on data from children who were a part of the initial clinical studies of this device. (19) Publications have reported positive outcomes for children using ventricular assist devices (VADs) as a bridge to transplantation. Using the United Network for Organ Sharing (UNOS) database, Davies et al. reported on use of VADs in pediatric patients undergoing heart transplantation. (20) Their analysis concluded that pediatric patients requiring a pretransplantation VAD have similar long-term survival to those not receiving mechanical circulatory support.
In 2011, Strueber et al. (21) published a case series of 50 patients awaiting heart transplantation treated with a newer generation HeartWare® VAD. This device was smaller than previous versions and implanted within the pericardial space. Patients were followed until transplantation, myocardial recovery, device explant, or death. The median duration of time on the LVAD was 322 days. Nine patients died; 3 from sepsis, 3 from multiple organ failure, and 3 from hemorrhagic stroke. At the end of follow-up, 20 patients had undergone transplant (40%), 4 had the pump explanted (8%), and the remaining 17 continued on pump support (34%). The most common complications were infection and bleeding. A total of 21 patients had infections (42%), and 5 patients had sepsis (10%). Bleeding complications occurred in 15 patients (30%), 10 of whom (20%) required surgery for bleeding.
The evidence on the efficacy of LVADs as bridge to transplant consists of numerous uncontrolled trials of patients who have no other treatment options. These studies report that substantial numbers of patients survive to transplant in situations in which survival would not be otherwise expected. Despite the lack of high-quality controlled trials, this evidence is sufficient to determine that outcomes are improved in patients who have no other options for survival. The impact of pre-transplant LVADs on survival from transplant is uncertain, with some studies reporting worse survival in patients receiving LVADs, but other studies reporting similar or improved survival.
LVADs as Destination Therapy
The policy regarding LVADs as destination therapy is based on a 2002 TEC Assessment (22) that offered the following observations and conclusions:
- The available evidence comes from a single, well-designed and rigorously conducted randomized trial, known as the REMATCH study. (23) The study was a cooperative effort of Thoratec, Columbia University, and the National Institutes of Health.
- The randomized trial found that patients with end-stage heart failure who are not candidates for cardiac transplantation have significantly better survival on a VAD compared with treatment by optimal medical therapy. Median survival was improved by approximately 8.5 months. Serious adverse events were more common in the VAD group, but these appear to be outweighed by this group’s better outcomes on function; New York Heart Association (NYHA) class was significantly improved, as was quality of life among those living to 12 months.
- VAD patients spend a greater relative proportion of time inside the hospital than medical management patients do, but the survival advantage would mean a longer absolute time outside the hospital.
Park and colleagues published an extended 2-year follow-up of patients in the REMATCH trial, which found that survival and quality-of-life benefits were still apparent. In addition, this study and other case series suggest continuing improvement in outcomes related to ongoing improvements in the device and in patient management. (24, 25) However, the durability of the HeartMate device used in the REMATCH trial is a concern; for example, at one participating institution, all 6 long-term survivors required device change-outs. Next generation devices consisting of smaller continuous flow devices are eagerly anticipated.
The main piece of evidence on the efficacy of LVADs as destination therapy in patients who are not transplant candidates is from a multicenter randomized controlled trial (RCT), the REMATCH study. This trial reported that the use of LVADs led to improvements in survival, quality of life, and functional status. This evidence is sufficient to establish that health outcomes are improved for this patient population.
Comparative efficacy of continuous flow versus pulsatile flow devices
In December 2009, Slaughter and colleagues published data from an unblinded randomized multicenter trial comparing a continuous flow device with a pulsatile device. (26) Subjects were randomly assigned to continuous-flow or pulsatile-flow devices on a 2:1 block-randomization basis. The primary outcome measured was a composite endpoint of 2-year survival, free of disabling stroke or need for device replacement. Continuous-flow patients (n=134) reached the primary outcome at a rate of 46% (95% CI: 38-55) compared to pulsatile-flow patients’ (n=66) rate of 11% (95% CI: 3-18), which was a significant difference (p<0.001). Analysis of constituent factors indicated that a lower rate of devices needing replacement in the continuous-flow group had the largest effect on the composite endpoint; 2-year death rate also favored this device (58% vs. 24%, respectively; p=0.008). Stroke and death (within 2 years of implantation) were similar in the 2 groups (stroke rate 12% and death rate 36%). Quality-of-life scores were also similar in the 2 groups. Although unblinded, this randomized trial adds to the evidence favoring continuous-flow devices.
Nativi et al. (27) published a non-randomized comparison of pulsatile versus continuous flow devices using data from the registry of the International Society for Heart and Lung Transplantation on 8,557 patients undergoing transplant. Comparisons were made among patients receiving a pulsatile LVAD, a continuous flow LVAD, and no LVAD. Two time periods were used for analysis, the first was pre-2004, when nearly all LVADs were pulsatile devices, and post-2004 when continuous use devices began to be used in clinical care. Comparing the first time period to the second time period, there was a significantly greater risk of mortality in the first time period compared to the second time period (relative risk [RR]: 1.30, 95% CI 1.03-1.65, p=0.03). When analysis was confined to the second time period, there was no significant improvement in survival for the continuous group compared to the pulsatile group (RR: 1.25, 95% CI: 1.03-1.65, p=0.03).
Other non-randomized studies that have compared outcomes from different types of LVADs have been smaller and/or focused on physiologic outcomes. (28-31) In some of these studies, the continuous flow devices exhibit greater improvement in physiologic measures, but none of these studies have reported significant differences between devices in clinical outcomes.
The evidence on the comparative efficacy of different devices consists of one RCT and several non-randomized comparative studies. The RCT reported fairly large differences in a composite outcome measure favoring the continuous flow devices, with increases in revision and reoperation rates for the pulsatile device group being the largest factor driving the difference in outcomes. Other non-randomized comparative studies, including one database study with large numbers of patients, have not reported important differences between devices on clinical outcomes.
Total Artificial Heart
TAH as Bridge to Transplant
The FDA approval of the CardioWest TAH was based on the results of a nonrandomized, prospective study of 81 patients. (32) Patients had failed inotropic therapy and had biventricular failure and thus were not considered appropriate candidates for an LVAD. The rate of survival to transplant was 79%, which was considered comparable to the experience with LVAD in patients with left ventricular failure. The mean time from entry into the study until transplantation or death was 79.1 days.
Other case series have been reported on outcomes of the TAH as a bridge to transplant. For example, Copeland et al. (33) reported on 101 patients treated with the SynCardia artificial heart as a bridge to transplant. All patients either met established criteria for mechanically assisted circulatory support, or were failing medical therapy on multiple inotropic drugs. The mean support time was 87 days, with a range of 1-441 days. Survival to transplant was 68.3% (69/101). Of the 32 deaths prior to transplant, 13 were due to multiple organ failure, 6 were due to pulmonary failure, and 4 were due to neurologic injury. Survival after transplant at 1, 5, and 10 years, respectively, was 76.8%, 60.5%, and 41.2%.
TAH as Destination Therapy
Data concerning the artificial heart are available from information concerning the FDA approval (34) and from a published article describing results for the first 7 patients. (35) The FDA indicated that their decision was based on the company's laboratory and animal testing and on a small clinical study of 14 patients conducted by Abiomed. The patients had a 1-month survival prognosis of not more than 30%, were not eligible for cardiac transplants, and were felt to not benefit from VAD therapy. The study was reported to show that the device is safe and has likely benefit for people with severe heart failure whose death is imminent and for whom no alternative treatments are available. Of the 14 patients in the study, 12 survived surgery. Mean duration of support for the patients was 5.3 months. In some cases, the device extended survival by several months; survival was 17 months in 1 patient. Six patients were ambulatory; 1 patient was discharged home. Complications included postoperative bleeding and neurologic events. Device-related infection was "non-existent."
This device shows technological progress, and these initial results are encouraging; however, a number of questions remain. These questions may be answered once the results of the 14-patient study are published, or data on a larger group of patients may be needed. One issue is to further analyze relevant patient outcomes (complications, quality of life, survival, etc.). Therefore, based on current information, this device is considered experimental, investigational and unproven.
There is a smaller amount of evidence on the use of TAH as a bridge to transplantation, or as destination therapy, compared to the use of LVADs. The type of evidence on bridge to transplant is similar to that for LVADs, i.e., case series reporting substantial survival rates in patients without other alternatives. Therefore, this evidence is sufficient to conclude that TAH improves outcomes for these patients similar to LVADs, and is a reasonable alternative for patients who require bridge to transplantation but who are ineligible for other types of support devices. There is insufficient evidence on the use of TAH as destination therapy to support conclusions.
Percutaneous ventricular assist devices (pVADs)
pVADs as an alternative to intra-aortic balloon pump (IABP) in cardiogenic shock
Three RCTs have been published that compare percutaneous ventricular assist device (pVAD) to IABP for patients with cardiogenic shock, (36-38) along with a systematic review and meta-analysis of these 3 trials. (39) The meta-analysis was published in 2009 by Chen et al. The 3 RCTs enrolled a total of 100 patients, 53 treated with a pVAD and 47 treated with an IABP. All 3 study populations included patients with acute myocardial infarction (MI) and cardiovascular shock; one of the trials (32) restricted this population to patients who were post revascularization in the acute MI setting. The primary outcomes reported were 30-day mortality, hemodynamic measures of left ventricular (LV) pump function, and adverse events.
All 3 trials reported an improvement in LV hemodynamics in the pVAD group. On combined analysis, there was a mean increase in cardiac index of 0.35 L/min/m2 for the pVAD group, an increase in mean arterial pressure of 12.8 mm Hg (95% CI: 3.6-22.0, p<0.001), and a decrease in pulmonary capillary wedge pressure of 5.3 mm Hg (95% CI: 1.2-9.4, p<0.05).
pVADS as Bridge to recovery in cardiogenic shock refractory to IABP
Case series of patients with cardiogenic shock refractory to IABP who were treated with pVAD have also been published. In the largest series, Kar et al. (41) treated 117 patients who had severe, refractory cardiogenic shock with the TandemHeart® System. Eighty patients had ischemic cardiomyopathy and 37 had nonischemic cardiomyopathy. There were significant improvements in all hemodynamic measures following LVAD placement. For example, cardiac index increased from 0.52±0.8 L/min/m2 to 3.0±0.9 L/min/m2 (p<0.001), and the systolic blood pressure (BP) increased from 75±15 mm Hg to 100±15 mm Hg (p<0.001). The authors concluded that pVAD rapidly reversed the terminal hemodynamic compromise noted in patients with severe refractory cardiogenic shock refractory to IABP and vasopressor support.
pVADs ancillary support in high-risk patients undergoing invasive cardiovascular procedures.
The PROTECT trial intended to evaluate whether the Impella® 2.5 system improved outcomes for patients undergoing high-risk percutaneous coronary intervention (PCI) procedures. PROTECT I (42) was a feasibility study of 20 patients who had left main disease or last patent coronary conduit that required revascularization but who were not candidates for coronary artery bypass graft (CABG) surgery. High-risk PCI was performed using the Impella® system for circulatory support. All of the procedures were completed successfully without any hemodynamic compromise during the procedures. There were 2 patient deaths within 30 days (10%), and 2 patients had a periprocedural MI (10%). An additional 2 patients had evidence of hemolysis, which was transient and resolved without sequelae.
The PROTECT II trial was a prospective, randomized clinical trial to compare the Impella® system with IABP in patients undergoing high-risk PCI procedures. Four hundred fifty two symptomatic patient with complex 3-vessel disease or unprotected left main coronary artery disease and severely depressed left ventricular function were randomly assigned to either IABP) (n=226) or Impella 2.5 (n=226) during nonemergent high-risk percutaneous coronary intervention. The authors noted in their results that Impella 2.5 provided superior hemodynamic support in comparison with IABP, with maximal decrease in cardiac power output from baseline of -0.04±0.24 W in comparison with -0.14±0.27 W for IABP (P=0.001). The authors also noted in their conclusions that at 90 days, trends for improved outcomes were observed for Impella 2.5-supported patients. (43)
A few other case series have described pVAD use in high-risk patients undergoing an invasive cardiac procedure. Sjauw et al. (44) performed a retrospective analysis of 144 consecutive patients undergoing high-risk PCI with pVAD support (Impella® system) from a European registry. Endpoints included successful device function and incidence of adverse events at 30 days. The device was successfully implanted in all 144 patients. There was one periprocedural death. The mortality rate was 5.5% at 30 days. Bleeding requiring transfusion or surgery occurred in 6.2% of patients, and vascular access site complications occurred in 4.0%. There was one stroke (0.7%) and no MIs were reported.
Kar et al. (45) reported on 5 patients who were treated with pVAD support during PCI. All patients were ineligible for CABG because of severe comorbidities. In 4 of 5 patients, the procedure was performed successfully and the pVAD removed within several hours. In the fifth patient, persistent cardiogenic shock precluded removal of the pVAD for more than 48 hours, and the patient eventually died of progressive heart failure 10 days after pVAD was discontinued. Giombolini et al. (46) treated 6 patients with pVAD who were undergoing a high-risk cardiac procedure. Three cases were performed on an emergency basis, and 3 were performed on an elective basis. There were no deaths, and all 6 procedures were successfully completed. The authors concluded the TandemHeart, a percutaneous transseptal ventricular assist device, can be easily and rapidly deployed either in emergency or in elective high-risk PCI to achieve complete cardiac assistance.
There is a substantial body of evidence from clinical trials and observational studies supporting implantable ventricular assist devices as a bridge to transplant in patients with end-stage heart failure, possibly improving mortality as well as quality of life. A well-designed clinical trial, with 2 years of follow-up data, demonstrates an advantage of implantable ventricular assist devices as destination therapy for patients who are ineligible for heart transplant. Despite an increase in adverse events, both mortality and quality of life appear to be improved for these patients. Therefore, LVADs may be considered medically necessary as a bridge to transplant and as destination therapy in patients who are not transplant candidates.
The evidence for total artificial heart in these settings is less robust. However, given the limited evidence from case series and the lack of medical or surgical options for these patients, TAH is likely to improve outcomes for a carefully selected population with end-stage biventricular heart failure awaiting transplant who are not appropriate candidates for an LVAD. TAH may be considered medically necessary for this purpose. There is insufficient evidence on the use of TAH as destination therapy, and TAH is considered experimental, investigational and unproven for this purpose.
The evidence on percutaneous ventricular assist devices (pVADs) indicates improved hemodynamic support in comparison with IABP therefore, pVADs that are FDA approved may be considered medically necessary when following the FDA approved indications.
Practice Guidelines and Position Statements
The American College of Cardiology/American Heart Association (ACC/AHA) released a guideline to the management of end-stage heart failure in 2005 (48); a 2009 focused update did not change any recommendations regarding the technologies covered in this policy. (49) The group has stated that left ventricular assist devices may be indicated in a highly select group of patients who are not candidates for heart transplantation and are likely to have a 1-year survival rate of less than 50% with medical therapy alone. The short-term use of any form of mechanical ventricular support is mentioned as an area of research interest. No recommendations are made regarding this indication.
The Heart Failure Society of America published guidelines in 2010 on surgical approaches to the treatment of heart failure. (50) The following recommendations were made regarding left ventricular assist devices:
- Patients awaiting heart transplantation who have become refractory to all means of medical circulatory support should be considered for a mechanical support device as a bridge to transplant. (Strength of Evidence = B)
- Permanent mechanical assistance using an implantable assist device may be considered in highly selected patients with severe HF [heart failure] refractory to conventional therapy who are not candidates for heart transplantation, particularly those who cannot be weaned from intravenous inotropic support at an experienced HF center. (Strength of Evidence = B)
- Patients with refractory HF and hemodynamic instability, and/or compromised end-organ function, with relative contraindications to cardiac transplantation or permanent mechanical circulatory assistance expected to improve with time or restoration of an improved hemodynamic profile should be considered for urgent mechanical circulatory support as a "bridge to decision." These patients should be referred to a center with expertise in the management of patients with advanced HF. (Strength of Evidence = C)
The European Society of Cardiology published guidelines in 2008 for the diagnosis and treatment of acute and chronic heart failure. (19) A focused update was published in 2010. (51) These guidelines included the following statements about LVADs:
- Current indications for LVADs and artificial hearts include bridging to transplantation and managing patients with acute, severe myocarditis (Class IIa recommendation, level of evidence C).
- LVAD may be considered as destination therapy to reduce mortality in patients with severe heart failure who are ineligible for transplant. (Class IIb recommendation, level of evidence B).
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