Evaluation of the HeartWare Ventricular Assist System for the Treatment of Advanced Heart Failure - ADVANCE BTT

Nov 14, 2010
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Author/Summarized by Author:
Dharam J. Kumbhani, MD, SM, FACC
Summary Reviewer:
Deepak L. Bhatt, MD, MPH, MBA, FACC
Trial Sponsor:
HeartWare, Inc., Framingham, MA
Date Presented:
01/01/2010
Date Updated:
11/14/2010
Original Posted Date:
11/14/2010
References

Description:

The current trial sought to compare the safety and efficacy of a new continuous flow ventricular assist device (VAD) (HeartWare), as compared with contemporary VADs.

Hypothesis:

The HeartWare VAD would be noninferior to contemporary VADs as a bridge to transplant (BTT) in patients listed for cardiac transplantation and in need of a mechanical support device.

Study Design

  • Blinded
  • Parallel

Patient Populations:

  • HeartWare: Age >18 years
  • BSA >1.2 m2
  • NYHA class IV
  • Listed for cardiac transplantation, UNOS Status 1A or 1B

  • INTERMACS: Listed for transplant at the time of implant
  • BSA ≥1.2 m2
  • Serum creatinine ≤5 without dialysis
  • Not on ventilator
  • First VAD

    Number of screened applicants: 157 (HeartWare)
    Number of enrollees: 137 (HeartWare)
    Duration of follow-up: 180 days
    Mean patient age: 53 years
    Percentage female: 26%
    Ejection fraction: 17.8%
    NYHA class: IV (100%)

Exclusions:

  • Major renal, hepatic, or pulmonary dysfunction
  • Recent cardiac transplant surgery
  • Recent myocardial infarction
  • Severe right ventricular failure
  • Aortic insufficiency without plans for correction
  • Patients with mechanical valves
  • Ongoing mechanical cardiac support other than IABP

Primary Endpoints:

  • Success, defined as survival on the originally implanted device, transplant, or explant for ventricular recovery (must survive 60 days post-explant) at 180 days

Secondary Endpoints:

  • Comparison of survival between treatment and control groups
  • Functional and QoL outcomes and adverse events in the treatment group
  • Functional status changes, measured by 6-minute walk test
  • QoL changes, measured by KCCQ and EuroQoL EQ-5D
  • Incidence of serious adverse events

Principal Findings:

A total of 140 patients were enrolled in the HeartWare group. The control group was comprised of 499 patients from the INTERMACS (Interagency Registry for Mechanical Assisted Circulatory Support) registry during the trial enrollment period. The mean body surface area in both groups was about 2.1 m2. About 82% of patients in the HeartWare group were on one inotrope at the time of enrollment, and 85% had a CRT-D device, whereas 25% also were on an intra-aortic balloon pump (IABP).

The primary endpoint of success (survival on the originally implanted device, transplant, or explant for ventricular recovery at 180 days) was noninferior between the HeartWare and control groups (92.0% vs. 90.1%, p < 0.001 for noninferiority, p = 0.62 for unadjusted superiority, p = 0.20 for adjusted superiority). Of 137 patients in the HeartWare group, 92% had undergone successful transplant or were still alive at 6 months (62.8% alive, 29.2% transplanted), and 4.4% required a device exchange. Survival was similar between the two groups at 360 days (90.6% vs. 85.7%, p = 0.39). Data for quality of life (QoL) measures were available for 79 patients in the HeartWare group. Significant improvements as compared with baseline were noted at 3 months, as measured by both KCCQ and EQ-5D VAS instruments. Six-minute walk distance was also significantly improved at 3 months, as compared with baseline in this group (237 m vs. 124 m, p < 0.05).

Complication rates were high in the HeartWare group, including 15% with bleeding requiring surgery, 10.7% with driveline infections, 6.4% with sepsis, 7.1% with ischemic strokes, 2.9% with hemorrhagic strokes, renal failure in 9.3%, respiratory failure in 19.3%, and hemolysis in 1.4%.

Interpretation:

The results of the ADVANCE BTT study indicate that the HeartWare VAD is noninferior to contemporarily implanted VADs in patients awaiting cardiac transplant. Survival was 94% at 6 months and 91% at 1 year. Complication rates in this highly morbid group of patients were high, although only 4.4% of the patients required implantation of another VAD/device exchange. These results are similar to those noted with currently available VADs.

The HeartWare VAD is a new continuous flow VAD, similar to the HeartMate II implantable VAD, which is used as both BTT and as destination therapy (DT). However, it is different from currently available VADs in that it has centrifugal flow design, as compared with axial flow in the HeartMate II VAD, and pulsatile flow in older VADs. As cardiac transplantation volume has more or less plateaued, there is great interest in mechanical support devices that are smaller and can be used not only as BTT, but also as DT. The HeartWare VAD offers potential advantages over currently available VADs as BTT in that it is implanted directly in the left ventricular apex and contained within the pericardial space, versus in a pump pocket, and thus may be better tolerated, with less infection and possibly bleeding.

While these preliminary short-term results are promising, further data are required. Importantly, the control group for this study was not randomized, but consisted of patients enrolled in the INTERMACS registry during the enrollment period of this study. Future randomized trials, including those directly comparing the HeartWare VAD to currently available continuous flow VADs (such as HeartMate II), are necessary.

References:

Presented by Dr. Keith Aaronson at the American Heart Association Scientific Sessions, Chicago, IL, November 14, 2010.

Keywords: Stroke, Sepsis, Heart-Assist Devices, Respiratory Insufficiency, Creatinine, Heart Transplantation, Renal Dialysis, Renal Insufficiency, Body Surface Area, Hemolysis, Communicable Diseases, Quality of Life, Pulsatile Flow, Hemorrhage


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