27

Use of Left Ventricular Assist Devices as Destination Therapy 

in End-Stage Congestive Heart Failure: A Systematic Review Evidence-based Synthesis Program

APPENDIX A. Technical Expert Panel Members

Inder Anand, MD, FRCP, DPhil

Director, Heart Failure Program

University of Minnesota Medical School

William Gunnar, MD, JD

National Director of Surgery

Department of Veterans Affairs

William Holman, MD

Chief, Surgical Services

Birmingham VA Medical Center

Gundars Katlaps, MD

Chief, Section of Cardiothoracic Surgery

Surgical Director, Programs of Heart Transplantation and Mechanical Assist Devices

Richmond McGuire VA Medical Center

Richard Schofield, MD, FACC

Chairman of Medicine

Malcolm Randal VA Medical Center

Chief, Medical Service

North Florida/South Georgia Veterans Health System

Josef Stehlik, MD

Director, VAMC Cardiac Transplant Program

VA Salt Lake City Health Care System
28

Use of Left Ventricular Assist Devices as Destination Therapy 

in End-Stage Congestive Heart Failure: A Systematic Review Evidence-based Synthesis Program

APPENDIX B. Search Strategy

Database: Ovid MEDLINE(R) <1948 to October Week 3 2011>

Search Strategy:

--------------------------------------------------------------------------------

1 exp Heart-Assist Devices/ or lvad.mp.

2 ventric$ assist.mp.

3 artificial ventricle.mp. 

4 heartware.mp. 

5 heartmate.mp. 

6 novacor.mp. 

7 coraide.mp. 

8 lionheart.mp. 

9 or/1-8 

10 limit 9 to (english language and humans and yr=”1995 -Current”) 

11 congestive heart failure.mp. or exp Heart Failure/ or cardiac failure.mp. or myocardial 

failure.mp. or ventricular dysfunction.mp. or exp Ventricular 

Dysfunction/ 

12 10 and 11 

13 limit 12 to (case reports or comment or editorial or letter) 

14 12 not 13 
29

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

eer Review Comments/Author Responses

REVIEWER COMMENT RESPONSE

nd methods for this review clearly described? 

rt that reviewing the evidence available for the use of the current 

devices as destination therapy. Given the very limited published data on 

uately addressed the three key questions required for this topic.

ibed and are standard for this type of evaluation. However, it should 

rent in ventricular assist devices (VADs) that importantly influence 

st, the control group in trials to date (e.g. optimal medical management 

cally ill. Survival of the control group in REMATCH was so poor that 

sidered ethically unacceptable for subsequent trials, unless the trial 

ts (e.g. the The Evaluation of VAD InterVEntion Before Inotropic Therapy 

 which will examine class IIIB patients). The REVIVE-IT trial itself faces 

hat cross-over from medical to device management during the trial. 

 IV heart failure will use approved devices as the control group. The 

 its limitations. 

t that the therapy cannot be blinded to the observers or the patient. The 

maximal oxygen consumption and six minute walk test is therefore 

heir evaluation

We have added a statement about use of more objective endpoints to the section on page 11 about patient outcomes for KQ1. We believe that although more objective endpoints such as exercise tests would be useful given the inability to blind comparisons between devices and non-surgical medical therapy, it is very difficult to translate changes in maximal exercise test parameters to effects on patients’ lives. Subjective patient outcomes could be less of an issue in unblinded comparisons of devices. 

written and focused. The objectives of the review were clearly defined, 

concise manner. The scope of the review was also well described and 

cient data to definitively answer one of the key points. The methods 

ble and consistent with evidence-based analysis of the data.

s are clearly described and appropriate for the potential therapy being 

s in our synthesis of the evidence? 

e bias in the synthesis of the evidence. The authors are to be 

ch to the key questions posed

of any bias and the Technical Expert Panel Members are noted experts 

idance and oversight
30

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

REVIEWER COMMENT RESPONSE

published studies that we may have overlooked?

st of the published and unpublished data on the subject from 1995 to 

 useful to include in this document the additional information in the latest 

 Interagency Registry for Mechanically Assisted Circulatory Support 

b site. According to this report, the total number of medical centers 

estination therapy have doubled from 69 to 135 as quoted by the authors 

ver a fifth of all LVADs have been implanted for destination therapy.

Updated information from the fourth annual INTERMACS report has been added to the Registry section on page 7. In addition, the INTERMACS website is now referenced there to provide access to up-to-date information. 

elated to HeartMate II

t was published in the February issue of the Journal of Heart and Lung 

ll not dramatically change the findings of the VA-ESP report, in my 

want to include the citation.

st device is currently under review by the FDA for the bridge-to

e worth mentioning this device as a future consideration, primarily due to 

n for the REVIVE-IT trial.

Updated information from the fourth annual INTERMACS report has been added to the Registry section on page 7. In addition, the INTERMACS website is now referenced to provide access to up to date information.We have now mentioned the HeartWare by name when discussing ongoing studies on pages 3, 17 and 23.

5):1593-9; discussion 1599-600. Epub 2011 Oct 31.

e with over 100 consecutive HeartMate II left ventricular assist 

an P, Colvin-Adams M, Boyle A, Shumway S, Joyce L, Liao K. 

ug;30(8):849-53. Epub 2011 Apr 29.

 gastrointestinal bleeding in patients with the HeartMate II left 

zu ZT, Radovancevic R, Hochman LF, Gregoric ID, Letsou GV, Kar B, 

an;31(1):1-8. Epub 2011 Oct 8.

 risk factors associated with neurologic complications in patients 

orted by a left ventricular assist device. Kato TS, Schulze PC, Yang 

H, Uriel N, Jorde U, Farr M, Naka Y, Mancini D. 

):1270-7. Infectious complications in patients with left ventricular 

omes in the continuous-flow era. Topkara VK, Kondareddy S, Malik F, 

azami N. 

The first report listed was screened but not included in this review because only 17 out of the 130 cases were destination therapy. The second report listed was screened but not included this review because most cases were not destination therapy. The article does point out the need to consider the risk and incidence of gastrointestinal bleeding as an important patient outcome particularly with continuous flow devices. Information about this important patient outcome was extracted whenever it was reported by studies that were included in the review.The third report listed was published after the literature search was done. It was not included this review because most cases used the older pulsatile flow HeartMate device that has become obsolete. Furthermore, the report doesn’t provide enough information to determine the predictive accuracy of identified risk factors for neurological complications. Judging by the magnitude of the differences, most likely the identified risk factors will not turn out to provide adequate discrimination. The article does point out the need to consider the risk and incidence of neurological complications as an important patient outcome. Information about this important patient outcome was extracted whenever it was reported by studies that were included in the review.The fourth report listed was screened but not included this review because most cases weren’t destination therapy, and the report doesn’t provide much information about patient selection based on the risk of infectious complications. The article does point out the need to consider the risk and incidence of infectious complications as an important patient outcome. Information about this important patient outcome was extracted whenever it was reported by studies that were included in the review.
31

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

REVIEWER COMMENT RESPONSE

w the following citation: “Moreno SG, Novielli N, Cooper NJ. Cost

 ventricular assist device HeartMate II for patients awaiting heart 

plant March 2012 (e-published ahead of print)”, and the accompanying 

Rogers, titled “Determining the cost-effectiveness of mechanical 

We have carefully reviewed both of these citations and decided against adding this cost-effectiveness analysis to the results section of the report because it took a UK National Health Service payer perspective and only looked at LVAD use as a bridge to heart transplant, However, the Moreno 2012 article does provide a good example of what could be done in a future in terms of a probabilistic cost-effectiveness analysis, so we incorporated information about this study into the Recommendations for Future Research Section on page 24. 

ations that have been overlooked or additional publications not included 

on of in any way change the conclusions that have been made.

mments

ntricular”

 which comparison the HR for all –cause death within 30 days refers to?

ry pressure > or < 25 mmHg?

Typographical error on page 4 corrected.The reference groups for the HR’s now have been noted.The article repeatedly states < 25 as indicated. The authors considered a low mean pulmonary artery pressure to be an indicator of right heart failure although others have associated worse outcomes with higher pulmonary pressures that can precipitate right heart failure after implantation of a left ventricular assist device.

s of health care providers and patients needs to be established for the 

ld generally preclude use of destination therapy.” Ideally, this would 

 trials directly. Estimating the risk benefit of a VAD on sub-populations 

al for error. If economic studies determine a minimum survival threshold 

VAD implantation to be cost-effective then it would be useful to develop 

 that threshold.

er patients I would state the name/details of registry as many will not 

 are talking about. They may assume you are suggesting the VA could/

We agree and have revised the statement on page 23 to, “Ideally clinical trials would be done to show that use of a prediction model improves patient outcomes. This review did not find any established or proposed threshold for predicted risk that would preclude use of destination therapy or generally be acceptable to patients and health care providers.” The INTERMACS registry has now been specified.

propriate supporting literature. 

ormation from INTERMACS defines risk factors for death following 

device. At this point in time, the information has not been reduced to a 

but probably will be in the near future. Dr. David Naftel at UAB can give 

 timeline for developing a system to predict outcome in mechanical 

uggestions
32

evices as Destination Therapy 

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REVIEWER COMMENT RESPONSE

ribing outcomes AFTER the clinical studies were concluded. You can 

 for patients getting devices WITHOUT being enrolled in clinical studies. 

o this particular clinical problem, but I think it warrants more attention.

ed on the comparison of newer devices to older ones, based on the 

ave been shown to improve survival v. nonsurgical management. But 

 is an alarming incidence of disabling strokes in patients with LVAD’s. 

 decision to have an LVAD implanted? Would patient’s be willing to 

urgical management in order to avoid the increased likelihood of a 

nted?

 consent also warrant attention. Are patients being made aware of the 

eing to implantation? (I appreciate this was not part of the charge of the 

Points well taken. Observational studies that directly compared outcomes in practice versus clinical trials were of interest as were reports of patient outcomes in case series. Many of these reports were from investigational sites and we couldn’t always tell if the report included or excluded patients that were enrolled in clinical trials. Hopefully, the INTERMACS registry data will provide better estimates of the incidences of all types of patient outcomes. The articles did not identify any additional patient outcomes that were not considered during the review. 

 no debate that use of the HeartMate II LVAD as compared to the 

e candidates leads to better outcomes, and that if compared to medical 

be more decidedly favorable. However it would be important for the 

urvival for DT patients with a HeartMate II was still only 55% at 2 years. 

 readers of the review and to policy makers. It is possible, perhaps even 

 will show improvement in the 2 year survival for DT patients supported 

pdates to this report are generated, such data would be of considerable 

nated. I am aware of anecdotes reporting very high 1 year survival rates 

m the INTERMACS data set) but to my knowledge these data are not yet 

on rates for patients who have undergone DT LVAD implantation? 

 to VA leadership. High rates of readmission post-operatively could 

siderable advantages of LVAD placement in this very ill population of 

eports that LVAD patients average >5 hospital readmissions over the first 

urely anecdotes. Data in this regard might be useful.

any patient who receives a DT LVAD via the Veterans Administration 

gistry and that patient outcomes should be followed over time. I would 

should be entered into the VA surgical quality improvement database, 

ady is established at every VA hospital with a surgical program on site. 

ent LVADs being placed by the VA as bridge to transplant should also be 

rder to track outcomes. 

ort, the authors note criteria established by the Centers for Medicare 

enters planning to initiate a DT LVAD program. The criteria included 

mum volume standards for the implanting surgeon, and facility disease

e Joint Commission. While VA would probably not be compelled to 

onders whether it would nevertheless be wise and prudent to do so 

m and to deflect external criticism which might be directed at the VA for 

vor.

The outcomes of using the HeartMate II as destination therapy study including the overall survival are summarized in the Executive Summary (page 3) and in the body of the report and evidence table. We have also cited other survival estimates in the report and added updated 2-year estimates from the INTERMACS registry on page 17. All estimates appear to be remarkably consistent with a trend to improved survival as patient selection and processes improve. Our search did not find good estimates of readmission rates or what complications caused them. The cost effectiveness estimates do include readmission rates of 0.21 per month for device therapy versus 0.13 for medical therapy, and the cost effectiveness ratio was sensitive to the presumed readmission rate as has been pointed out in the report.The VA surgical quality improvement data base has been added to the recommendation. We agree, and had summarized the CMS criteria and other guidelines in the report to facilitate consideration by VA policymakers. 
33

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

REVIEWER COMMENT RESPONSE

pertain to Key Question #2 regarding site characteristics associated with 

 trend in the U.S for “non-transplant” centers to establish stand-alone 

hese programs that have minimal to no transplant experience and have 

ng LVADs as BTT will have similar outcomes in an older and potentially 

ossible that the VA system will need to address the question of whether 

omic sense to allow a LVAD DT program in a VA hospital without an 

t includes experience and expertise in the evaluation of heart transplant 

me data in the next 3 – 5 years to help resolve this issue.

dations on how this report can be revised to more directly address or assist implementation needs.

emarkable technologic advancements have resulted in improved device 

onditional reimbursement until after the Slaughter study was published.

picts the status quo of mechanical circulatory support. 

ss for accrediting mechanical circulatory support programs that may be 

ration. The requirements for this specialized accreditation describe in 

d infra-structure that are required for a mechanical circulatory support 

d for creation of a balanced, thoughtful and well written report.
34

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

vidence Tables

 on Patient Outcomes

lusion Criteria Baseline Characteristics Comparison Patient Outcomes Study Quality

ia:

eart transplant

ptimal medical  ejection 

onsumption 

f able to 

b or IV 

45 out of last 

BP for 7 days, 

inotrope for 14 

ria:

h surgical risk

ex > 40 kg/m2

 transplant

dition or ired protocol 

tory disease

ne > 3.5 mg% 

sis

ition that could 

 < 3 years

 not listed here

n = 200Mean Age (yr): 62 Male: 84% White: 74% Mean LVEF: 17%IV inotrope: 79%IABP: 22%Mech. Vent.: 8%ICD: 82%CRT: 60%NYHA class:III - 22%IV - 69%

Investigational (I):HeartMate II continuous flow LVAD with warfarin (n=134)(1 received the control LVAD)Control (C): HeartMate XVE pulsatile flow LVAD without warfarin (n=66)(3 received the investigational LVAD)Median time on LVAD:I – 1.7 yearsC – 0.6 years

Primary composite endpoint of survival free of disabling stroke or reoperation to remove device including urgent heart transplant at 24 months

I – 46% vs C – 11% (p<0.001)HR = 0.38 (95% CI 0.27 to 0.54)

First events:Death

I - 33% vs C - 41% (p=0.05)HR = 0.59 (95% CI 0.35 to 0.99)

Device Removed

I - 10% vs C - 36% (p<0.001)HR = 0.18 (95% CI 0.09 to 0.37)

Disabling Stroke

I - 11% vs C - 12% (p=0.56)HR = 0.78 (95% CI 0.33 to .82)

As treated actuarial 1 and 2 year survival estimates ignoring device replacements (overall p=0.008 with HR = 0.54 (95% CI 0.34 to 0.86) )

I (n=133): 68% (1 year) and 58% (2 year)C (n=59): 55% (1 year) and 24% (2 year)

% of follow-up time spent as outpatient

I – 88% vs C – 74% (p=0.02)

Median initial length of stay

I – 27 vs C – 28 days

Readmission rate (per person year)

I – 2.6 vs C – 4.2 (p=0.02)

RandomizedGroups similar at 

baseline with no need for further adjustment 

Not blindedWithdrawals 

explained

Intention to Treat 

(ITT) analysis of primary outcome; other outcomes analyzed as treated 

Adequate number 

and precision of estimates
35

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

lusion Criteria Baseline Characteristics Comparison Patient Outcomes Study Quality

See above See above NYHA class I /II among survivors at 1-year

I (n=72) - 76% vs C (n=18) - 61%) (p=0.22)Mean LHFQ Score among survivors at 1-year (lower better)I (n=76) - 34 vs C (n=19) - 44 (p=0.03)Mean KCCQ Clinical Score among survivors at 1-year (higher better)I (n=76) - 69 vs C (n=18) - 61 (p=0.12)Selected Adverse Event Rates (per person yr)

I C p-value

Stroke 0.1 0.5 <0.001Sepsis 0.4 1.1 <0.001 Major bleed 1.6 2.4 0.06Right heart failure

0.1 0.5 <0.001

Respiratory failure

0.3 0.8 <0.001

Cardiac arrhythmia requiring treatment

0.7 1.3 0.006

Renal failure 0.1 0.3 <0.001

See above
36

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

lusion Criteria Baseline Characteristics Comparison Patient Outcomes Study Quality

ess protocol 

usion/exclusion 

ous study 

91) 

n = 414Mean Age (yr): 63Male: 79% Mean LVEF: 17%IV inotrope: 78%IABP: 20%Mech. Vent.: 5%ICD: 83%CRT: 61%NYHA class:III - 34%IV - 66%Predicted 1-year survival without device: 41%

All received HeartMate II Early enrollees (EE) in RCT from 3/2005 to 5/2007 (n=133), reported previouslyLater enrollees (LE) in non-randomized continued access protocol from 5/2007 to 3/2009 (n=281)Median duration of device use: EE 1.7 vs LE 2.1 yrs

Primary composite endpoint - survival free of disabling stroke or reoperation to remove device including urgent heart transplant at 24 months

EE – 50% vs LE – 59% (p=0.07)

Actuarial 1 and 2 year survival

EE: 68% (1 year) and 58% (2 year)LE: 73% (1 year) and 63% (2 year)overall p=0.21 

Median initial length of stay

EE – 27 vs LE – 23 days (p=0.09)

Readmission rate (per person year)

I – 2.6 vs C – 4.2 (p=0.02)

NYHA class I or II among survivors at 1-year

EE (n=73) - 77% vs LE (n=161) - 77%

Mean LHFQ Score among survivors at 6-months(lower better)

EE (n=86) - 30 vs LE (n=184) - 38 over 2 years p=0.04

Mean overall KCCQ Score among survivors at 6-months (higher better)

EE (n=86) - 64 vs LE (n=187) - 70 over 2 years p=0.08

Not randomizedGroups similar at 

baseline with no need for further adjustment 

Not blindedWithdrawals not 

explained

Intention to Treat 

(ITT) analysis 

Adequate number 

and precision of estimates

Selected Adverse Event Rates (per person yr) 

EE LE p-value

Ischemic stroke 0.06 0.05 0.48

Hemorr. stroke 0.07 0.03 0.01

Sepsis 0.38 0.27 0.02 

Device infection 0.47 0.27 <0.001

Major bleed 1.89 1.27 <0.01

Right heart failure 0.16 0.13 0.39

Cardiac arrhythmia requiring treatment

0.69 0.46 <0.01

Renal failure 0.10 0.06 0.11

Pump replacement 0.06 0.04 0.35
37

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

lusion Criteria Baseline Characteristics Comparison Patient Outcomes Study Quality

es of 

rapy

n=385Mean Age (yr): 62Male: 84%White: 76%Contraindications for Heart Transplant

Age: 33%Renal: 22%Obesity: 16%Pulmonary: 20%

Preop Profile:

Shock: 9%Declining: 41%Inotrope: 26%Recurrent: 15%

HeartMate II (HMII) continuous flow LVAD (n=281)HeartMate XVE (HMXVE) pulsatile flow LVAD (n=104)

Actuarial Survival HMII HMXVE

Month 3 86% 83%Month 6 81% 70%Month 12 74% 61%Month 24 na 39%

p=0.02 (censored at transplant or device removal)

Not RandomizedBaseline similarity 

not reported

Different time 

periods

No adjustmentsNot blindedLosses to follow-up 

not reported

Intention to Treat 

(ITT) analysis 

Adequate number 

and precision of estimates

ases; selection 

destination 

scribed 

n= 31Mean age (yr): 52 Otherwise not described

HeartMate II continuous flow LVAD used as destination therapyNo control group

80% 3-month survival71% 6-month survival71% 1-year survival Other outcomes not reported for destination therapy subgroup

Small retrospective unblinded case series without a control group or description of baseline characteristics or follow-up

, IABP – intra-aortic balloon pump, IV – intravenous, ICD - implanted cardiac defibrillator, CRT - cardiac resynchronization therapy, LVAD - left 

rd ratio, CI - confidence interval, LHFQ - Minnesota Living with Heart Failure Questionnaire with lower scores indicating the patients perceived 

on their quality of life, KCCQ - Kansas City Cardiomyopathy Questionnaire - the clinical score is a measure of physical function and heart failure 

ting less symptoms and better function
38

evices as Destination Therapy 

Failure: A Systematic Review Evidence-based Synthesis Program

ent Selection

lusion 

Sample of Patients Outcomes & Baseline Correlates Study Quality

ia:

d in 

st 

ed as 

rapy 

6 to 

0

n = 385HeartMate II (n=281, 73%) HeartMate XVE (n=104, 27%)Mean Age (yr): 62 Male: 84% White: 76%Black: 18% INTERMACS CLASSIFICATIONCardiogenic shock: 9%Progressive decline: 41%Inotrope dependent: 26%Recurrent decompensated heart failure: 15%Greatly limited exertion: 7%Class IIIb: 2%REASONS NOT ELIGIBLE FOR HEART TRANSPLANTAdvanced age: 33%Renal dysfunction: 22%High body mass index: 16%Pulmonary hypertension: 12%Other: 17%

Unspecified number and names of variables tested; reference groups for HR’s are the complements of those described1) All-cause death within 30 days, n=35

a) cardiogenic shock 

HR = 3.5, p<0.01

b) need for concomitant surgery

HR = 3.0, p=0.02

c) 10 units higher BUN 

HR = 1.3, p=0.001

2) All-cause deaths after 30 days, n=62

a) HeartMate XVE vs HeartMate II

HR = 2.75, p=0.002interactions with other predictors not reported

b) pulmonary hypertension

HR = 3.6, p=0.0001

c) 10 units lower sodium

HR = 2.1, p=0.005

d) diabetes

HR = 2.0, p=0.01

e) age 70 vs 60 years

HR = 1.8, p<0.0001

Patients eligible for destination therapy, but not all received HeartMate II Most variables assessed before implantation surgeryMeasurements of potential predictors not standardized or describedPresumably complete follow-up of deaths Most predicted probabilities and confidence intervals not reported, no calibration or validation of prediction modelNo assessment of whether or how much use of variables could improve patient selection or outcomes

ia

clinical 

te 

on 

red 

cal 

ATCH 

n=129 (some missing values needed for the prediction model were imputed and use of inotropes or an intra-aortic balloon pump and/or ventilator were added to the prediction model)n= 61 in medical therapy armMean Age (yr): 67 Male: 80% Mean LVEF: 17%NYHA class IV: 100%IV inotrope: 56%Intra-aortic balloon pump: 8%Defibrillator: 35%

Survival predictions made using variables in the Seattle Heart Failure ModelAverage estimated 1-YEAR SURVIVAL in medical therapy arm (n= 37 deaths) 30% vs 28% observed81% had < 50% estimated 1-year survivalNote: guidelines for destination therapy recommend patient’s expected 1-year survival be < 50%Interaction between treatment effect (assist device versus medical therapy) and Seattle Heart Failure Score was not significant (p=0.86)

Patients eligible for destination therapy, but none received HeartMate II Variables assessed before implantation surgeryMeasurements of potential predictors not standardized or describedComplete follow-up for deathsNo confidence intervals on predicted probabilities in small groups, a little information about calibration and validity of predictionsLittle assessment of whether or how much use of variables could improve patient selection or outcomesNo evidence risk score discriminates groups of patients that do or do not have a survival benefit 
39

evices as Destination Therapy 

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lusion 

Sample of Patients Outcomes & Baseline Correlates Study Quality

ia

ate 

ation 

DA 

mber 

n 

 case 

9 

n= 280 (222 with complete data for analysis of in-hospital mortality)Mean Age (yr): 61 Male: 82% Mean LVEF: 18%IV inotrope: 70%NYHA class IV: 100%

Numerous variables examined by stepwise logistic regression including demographics and body size, cause of heart failure, history of cardiovascular diseases, other comorbidities, medical and device therapy for heart failure, hemodynamics, laboratory data, year and center experience. Regression estimates used to calculate individual risk score.90-DAY IN-HOSPITAL MORTALITY, n=60 (27%)

CAUSESSepsis - 33%Multiorgan failure - 20%Right heart failure - 14%Respiratory failure - 7%Technical difficulties - 5%Device failure - 5%Hemorrhage - 3%Stroke - 3%Several other causes - 10%INDEPENDENT CORRELATES(OR = odds ratio)Platelet count < 148,000; OR = 7.7 Serum albumin < 3.3 g/dl; OR = 5.7INR > 1.1; OR = 5.4Vasodilator; OR = 5.2Mean pulmonary artery pressure < 25 mmHg; OR = 4.1Aspartate aminotransferase > 45 U/ml; OR = 2.6Hematocrit < 34%; OR = 3.0Blood urea nitrogen > 51 U/dl; OR = 2.9No IV inotrope; OR = 2.9

Patients eligible for destination therapy, but none received HeartMate II Variables assessed before implantation surgeryMeasurements of potential predictors not standardized or describedPresumably complete follow-up of in-hospital deathsWide confidence intervals on predicted probabilities, calibration questionable, and predictions not validatedNo assessment of whether or how much use of variables could improve patient selection or outcomes; thresholds of acceptable operative risk not defined
40

evices as Destination Therapy 

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lusion 

Sample of Patients Outcomes & Baseline Correlates Study Quality

See above RISK SCORE

C-statistic 0.89

RISK SCORE CATEGORIES 

% PREDICTED (CI) vs OBS

0 to 8 (n=65) 2 (1 to 5) vs 69 to 16 (n=111) 12 (8 to 18) vs 1417 to 19 (n=28) 44 (33 to 56) vs 61>19 (n=18) 81 (66 to 91) vs 82

See above

a

ed 

of 

I 

st 

eened 

 

d CMS 

n=55 subgrouped into < 70 (n= 25) and ≥ 70 years old (n=30)Male: not reportedNYHA class IV: 100%Mean LVEF: 20%IV inotrope: 64%Intra-aortic balloon pump: 5%Defibrillator: 74%Cardiac resynchronization therapy: 51%Mean Destination Therapy Risk Score: 9.3

< 70 ≥70group group

MEAN AGE (years) 57 76MEDIAN DURATION WITH DEVICE (days)

415 482

DROPOUTS 3 0SURVIVAL (p=0.81)

30 days 96% 97%6 months 88% 83%12 months 72% 75%

AT 6 MONTHS

NYHA CLASS I or II 100% 89% p=0.35MEAN IMPROVE in MLHFQ SCORE

36 42 p=0.07

MEAN IMPROVE in KCCQ SCORE

32 42 p=0.88 

ADVERSE EVENT RATES No significant differences

Major Bleeding 28% 30%Sepsis 24% 20%Device-related infect. 20% 17% Cardiac Arrhythmia 32% 33%Stroke 8% 10%Right heart failure 4% 3%Renal failure 4% 3% 

Patients eligible for destination therapy, received HeartMate II Age determined before implantation surgery and likely valid Presumably complete follow-up in trials No confidence intervals on differences between small age subgroups No adjustment for preoperative differences

y for Mechanically Assisted Circulatory Support, LVEF – left ventricular ejection fraction, IV – intravenous, NYHA – New York Heart Association, 

INR – international normalization ratio, CI – 95% confidence interval, OBS – observed, BUN – blood urea nitrogen, MLHFQ – Minnesota Living 

ansas City Cardiomyopathy Questionnaire
41

evices as Destination Therapy 

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t-effectiveness

Model Components and Source Base Case Sensitivity Analyses Range in ICER per QALY* Study Limitations

urvival for LVAD1

urvival for OMM2

rm survival extrapolation for LVADrm survival extrapolation for OMM3

mplantation hospital cost4mplantation professional service cost5

placement cost6

 LVAD replacement rate 1

talization cost (per event)7,8

 rehospitalization rate for LVAD1 rehospitalization rate for OMM7 outpatient costs9,10ife cost11

r NYHA Class I12r NYHA Class II12r NYHA Class III12r NYHA Class IV12

KM curve KM curve 

Exponential Exponential

$193,812 

$8,841 

$131,430 

0.005 

$6,850 

0.21 

0.1325 $2,331 

$44,211 

0.855 0.771 0.673 0.532

NA NA 

Linear, Stop and drop

NA 

$122,785–$264,839

NANA NA

$6,850–$30,627 

NA

0.1325-0.26 

NANA

0.641-1.0 

0.578-0.9640.505-0.8410.399-0.665

NANA

$180,000-$375,000

NA

$150,000-$250,000

NANANA

$200,000-$280,000

NA

$195,000-$200,000

NANA

$180,000-$230,000$175,000-$225,000$190,000-$205,000$190,000-$200,000

The data regarding the difference in the effect of LVAD vs. OMM involves an indirect comparison across 2 RCTsThe long-term outcome data are extrapolated from 2 years of RCT dataAll sensitivity analyses only varied one parameter at a time, whereas a probabilistic model that allows multiple parameters to vary at the same time might more accurately assess the overall uncertainty in the modelUtilities used to calculate qualityadjusted life years were based on NYHA classes

 OMM - optimal medical management, NYHA - New York Heart Association, RCT – randomized controlled trial, ICER- incremental cost

justed life year

st Effectiveness Ratio per Quality Adjusted Life Year when the model is varied over the range of values in the sensitivity analysis. The values 

ately the nearest $5,000 using Figure 3 from Rogers et al., 2012.35

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