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Efficacy of the HeartWare Ventricular Assist System in Bridging Adult
Heart Failure Patients to Transplantation: A Systematic Review.
Anne Mastrandrea
Pacific University School of Physician Assistant Studies, Hillsboro, OR USA
Purpose
The purpose of this paper is to perform a systematic review
of the literature on the use of the HeartWare Ventricular
Assist System in bridging heart failure patients to
transplantation. The body of evidence will be evaluated
using the Grading of Recommendations Assessment,
Development and Evaluation (GRADE) tool developed by
the GRADE Working Group.
Method
An extensive literature search was conducted using
Medline, CINHAL, and Evidence-Based Medicine Reviews
Multifile. These databases were accessed through the
Pacific University Library system. The keywords searched,
individually and in combination, included: “HeartWare,
HVAD, and transplant”. The search was limited to human
subjects, the English language, and articles published since
the year 2000. Only the articles that included “HeartWare,
HVAD, and transplant” in combination were included. This
resulted in four articles and, of these, only one was a
clinical trial which was included in this systematic review.
To find more articles, the first clinical trials’ primary author
G.M. Wieselthaler was searched which resulted in 19
articles. Of these articles only two were clinical trials on the
HeartWare Ventricular Assist System, one was the first
clinical trial found and the other article was new and is
included in the review.
The second clinical trial by Strueber et al. (2011) was the same type
of study, had the same goals, and took place in the same locations as
in the first study. The trial enrolled 50 NYHA class IV patients on
intravenous inotropic therapy between March 2006 and December
2008. The primary end points were survival to cardiac transplant,
survival to 180 days, or cardiac recovery enough to explant the
pump. The survival rates to transplantation, cardiac recovery with
device explant, or ongoing cardiac support with the device was 90%
at 180 days, 84% at one year, and 79% at two years. These results
were compared with the Seattle Heart Failure Model (SHFM) which
theoretically estimated the survival of the study group if they had
only received medical therapy instead of the assist device. The
SHFM estimated the cohort survival to180 days at 73 ± 3%, 58 ±
4% at one year, and 40 ± 4% at two years. The authors of this study
also concluded that the HVAD system is safe and effective.
Discussion
These clinical trials showed promising results that the HeartWare
HVAD system is safe and effective in bridging adult heart failure
patients to transplant. Unfortunately these trials had limitations that
affect the quality of the data. Both of the trials had small population
sizes, only measured the outcomes of one intervention, and had
authors who had received grants from the makers of the HeartWare
HVAD system. All of these limitations introduce bias and affect how
the study was conducted and how the data was reported.
Survival to
2 cohort
High
transplant (observational) survival
Efficacy of the
HeartWare
Ventricular
Assist System
in bridging
Survival
adult heart
2 cohort
High
failure patients 180 days
(observational) survival
on device
to
transplantation
Low
0
0
0
0
0
+1 0 0 Moderate
Dose-Response
Confounders
Findings
Large Magnitude
Outcome
Publication Bias
Comparison
Quantity and
type of
evidence
Grade of
Overall
Evidence
GRADE of
for
Evidence
Outcome
Precision
Decrease GRADE
Increase
GRADE
Directness
The clinical trial by Wieselthaler et al. (2010) was a prospective,
non-randomized, single-arm clinical trial that looked at the efficacy
of the HeartWare HVAD system as a bridge to transplant in
refractory end-stage heart failure patients. Twenty-three patients
were enrolled between March 2006 and November 2007 at five
hospitals in Europe and Australia. All 23 patients were receiving
intravenous inotropic therapy and were in end-stage heart failure
(class IV New York Heart Association (NYHA) functional
classification of heart failure). The end points of the study were
survival to cardiac transplantation or to 180 days on the device. The
results of this first study showed that survival was 91% at 180 days
and 86% at one year on the device. The authors of the study claim
the results are comparable to initial clinical trials of other left
ventricular assist devices, which demonstrates efficacy and safety of
the device.
Consistency
Heart failure affects approximately 5.8 million people in the
U.S. alone and has a high mortality rate with 20% dying
within the first year after diagnosis. Heart failure can be
caused by an array of disorders and diseases including
congenital heart disease, hypertension, valvular heart
disease, coronary artery disease, and/or diabetes. Treatment
is difficult as the disease progresses and is aimed at
symptom control, stopping or reversing myocardial
dysfunction, and reducing mortality. Today the gold
standard treatment of end-stage heart failure is cardiac
transplantation. Unfortunately, there is a higher need for
organs than there are donors by a factor of 10 and thus,
many patients die awaiting transplant. Recently, left
ventricular assist devices (LVADs) have been bridging
patients to transplantation, but they come with many
complications including infection, bleeding, and
thromboembolism. The HeartWare HVAD system is a
promising new smaller LVAD that claims to be more
durable than the current LVADs on the market today and
will hopefully improve the survival of heart failure patients
awaiting transplant.
GRADE Table
Study Quality
Results
Starting grade
Introduction
Moderate
Low
0
0
0
0
0
+1 0 0 Moderate
Conclusion
The HeartWare HVAD system is a new type of LVAD that is considerably smaller than its competitors and claims
to be more durable, allowing it to function for a longer period of time. In the first clinical trials, the system is
shown to have comparable, if not better survival rates than other LVADs with end-stage heart failure patients
awaiting transplantation. The GRADE system showed that these trials have a ‘moderate’ quality of evidence for
use in similar patient populations. In conclusion the HeartWare HVAD system has been shown to be safe and
effective in bridging adult heart failure patients to cardiac transplantation.
References
Colucci, W.S. & Pina, I.L. (2010). Indications and contraindications for cardiac transplantation. UpToDate. Retrieved from http://www.uptodate.com/contents/indications-and-contraindications-for-cardiac-transplantation
Colucci, W.S. (2010). Management of refractory heart failure. UpToDate. Retrieved from http://www.uptodate.com/contents/management-of-refractory-heart-failure
The Grading of Recommendations Assessment, Development and
Evaluation (GRADE) system was used to evaluate the quality of
outcomes and recommendations of these trials. Both trials were
observational studies and thus start out with a ‘low’ quality of
evidence. From there the clinical trials were upgraded to ‘moderate’
because it was determined that they had a large magnitude of effect
(meaning the patients in the study represented the same type of
patients needing this intervention even if the study size was small).
The recommendation of using the HVAD system was considered
‘strong’ based on the fact that the quality of evidence is ‘moderate’
and the benefits of this intervention outweigh the harms.
Acknowledgements: Cras commodo. Sed magna mauris, iaculis eu, aliquam rhoncus, rutrum et, nulla. Phasellus ligula. Vestibulum tempor ipsum eu nunc
Colucci, W.S. (2009). Overview of the therapy of heart failure due to systolic dysfunction. UpToDate. Retrieved from http://www.uptodate.com/contents/overview-of-the-therapy-of-heart-failure-due-to-systolic-dysfunction
Guyatt GH, Oxman AD, Vist G, Kunz R, Falck-Ytter Y, Alonso-Coello P, Schünemann HJ, for the GRADE Working Group. (2008). Rating quality of evidence and strength of recommendations GRADE: an emerging
consensus on rating quality of evidence and strength of recommendations. BMJ, 336, 924-926. doi: 10.1136/bmj.39489.470347.AD
Jeevanandam, V., & Eisen, H.J. (2010). Intermediate and long-term mechanical cardiac support. UpToDate. Retrieved from http://www.uptodate.com/contents/intermediate-and-long-term-mechanical-cardiac-support
LaRose, J.A., Tamez, D., Ashenuga, M., & Reyes, C. (2010). Design concepts and principle of operation of the heartware ventricular assist system. American Society of Artificial Internal Organs Journal, 56, 285-289. doi:
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Lloyd-Jones D, Adams, R.J., Brown, T.M., Carnethon, M., Dai, S., De Simone, G. ...Wylie-Rosett, J. (2010). Heart disease and stroke statistics- 2010 update. Circulation 121: e1-e170.
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Strueber, M., O’Driscoll, G., Jansz, P., Khaghani, A., Levy, W., & Wieselthaler, G. (2011). Multicenter evaluation of an intrapericardial left ventricular assist system. Journal of the American College of Cardiology, 57, 13751382. doi: 10.1016/j.jacc.2010.10.040
Wieselthaler, G.M., O’Driscoll, G., Jansz, P., Khaghani, A., & Strueber, M. (2010). Initial clinical experience with a novel left ventricular assist device with a magnetically levitated rotor in a multi-institutional trial. The
Journal of Heart and Lung Transplantation, 29, 1218-1225. doi: 10.1016/j.healun.2010.05.016