1. 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 Results 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. 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. 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. Introduction 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. 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. 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-transplantationhttp://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-failurehttp://www.uptodate.com/contents/management-of-refractory-heart-failure 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-dysfunctionhttp://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-supporthttp://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: 10.1097/MAT.0b013e3181dfbab5 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. doi:10.1161/CIRCULATIONAHA.109.192667 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, 1375- 1382. 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 Acknowledgements: Cras commodo. Sed magna mauris, iaculis eu, aliquam rhoncus, rutrum et, nulla. Phasellus ligula. Vestibulum tempor ipsum eu nunc GRADE Table ComparisonOutcome Quantity and type of evidence Findings Starting grade Decrease GRADE Increase GRADE Grade of Evidence for Outcome Overall GRADE of Evidence Study Quality Consistency Directness Precision Publication Bias Large Magnitude Dose-Response Confounders Efficacy of the HeartWare Ventricular Assist System in bridging adult heart failure patients to transplantation Survival to transplant 2 cohort (observational) High survival Low00000+100Moderate Survival 180 days on device 2 cohort (observational) High survival Low00000+100Moderate