Use of Left Ventricular Assist Devices as Destination Therapy in End-Stage Congestive Heart Failure: A Systematic Review Evidence-based Synthesis Program Table 2. Key Question #2: Patient Selection Study/Country/ Inclusion/Exclusion Funding Sample of Patients Outcomes & Baseline Correlates Study Quality Criteria Source Kirklin 20113 Inclusion Criteria: n = 385 Unspecified number and names of variables Patients eligible for destination therapy, but Case registered in HeartMate II (n=281, 73%) tested; reference groups for HR’s are the not all received HeartMate II 69 centers in INTERMACS complements of those described Most variables assessed before implantation U.S. HeartMate XVE (n=104, 27%) surgery FDA-approved 1) All-cause death within 30 days, n=35 Funding ventricular assist Mean Age (yr): 62 a) cardiogenic shock Measurements of potential predictors not Source: NIH, device implanted as Male: 84% HR = 3.5, p<0.01 standardized or described others destination therapy White: 76% b) need for concomitant surgery Presumably complete follow-up of deaths from June, 2006 to Black: 18% HR = 3.0, p=0.02 September 2010 c) 10 units higher BUN Most predicted probabilities and confidence INTERMACS CLASSIFICATION HR = 1.3, p=0.001 intervals not reported, no calibration or Cardiogenic shock: 9% validation of prediction model Progressive decline: 41% 2) All-cause deaths after 30 days, n=62 No assessment of whether or how much use Inotrope dependent: 26% a) HeartMate XVE vs HeartMate II of variables could improve patient selection or Recurrent decompensated heart HR = 2.75, p=0.002 outcomes failure: 15% interactions with other predictors not Greatly limited exertion: 7% reported Class IIIb: 2% b) pulmonary hypertension HR = 3.6, p=0.0001 REASONS NOT ELIGIBLE FOR c) 10 units lower sodium HEART TRANSPLANT HR = 2.1, p=0.005 Advanced age: 33% d) diabetes Renal dysfunction: 22% HR = 2.0, p=0.01 High body mass index: 16% e) age 70 vs 60 years Pulmonary hypertension: 12% HR = 1.8, p<0.0001 Other: 17% Levy 200933 Inclusion Criteria n=129 (some missing values Survival predictions made using variables in the Patients eligible for destination therapy, but none 20 centers in Participants in clinical needed for the prediction Seattle Heart Failure Model received HeartMate II U.S. trial of HeartMate model were imputed and use Variables assessed before implantation surgery VE for destination of inotropes or an intra-aortic Average estimated 1-YEAR SURVIVAL in Measurements of potential predictors not Funding therapy compared balloon pump and/or ventilator medical therapy arm (n= 37 deaths) standardized or described Source: to optimal medical were added to the prediction 30% vs 28% observed Thoratec Corp therapy (REMATCH model) Complete follow-up for deaths Study) n= 61 in medical therapy arm 81% had < 50% estimated 1-year survival No confidence intervals on predicted Note: guidelines for destination therapy probabilities in small groups, a little information Mean Age (yr): 67 recommend patient’s expected 1-year survival be about calibration and validity of predictions Male: 80% < 50% Little assessment of whether or how much use Mean LVEF: 17% Interaction between treatment effect (assist of variables could improve patient selection or NYHA class IV: 100% device versus medical therapy) and Seattle Heart outcomes IV inotrope: 56% Failure Score was not significant (p=0.86) No evidence risk score discriminates groups of Intra-aortic balloon pump: 8% patients that do or do not have a survival benefit Defibrillator: 35% 38 Use of Left Ventricular Assist Devices as Destination Therapy in End-Stage Congestive Heart Failure: A Systematic Review Evidence-based Synthesis Program Study/Country/ Inclusion/Exclusion Funding Sample of Patients Outcomes & Baseline Correlates Study Quality Criteria Source Lietz 200711 Inclusion Criteria n= 280 (222 with complete Numerous variables examined by stepwise Patients eligible for destination therapy, but Use of HeartMate data for analysis of in-hospital logistic regression including demographics none received HeartMate II 56 centers in XVE for destination mortality) and body size, cause of heart failure, history of U.S. therapy after FDA cardiovascular diseases, other comorbidities, Variables assessed before implantation approval, November Mean Age (yr): 61 medical and device therapy for heart failure, surgery Funding 2002 – 2005 Male: 82% hemodynamics, laboratory data, year and center Source: not experience. Regression estimates used to Measurements of potential predictors not reported Consent to be in Mean LVEF: 18% calculate individual risk score. standardized or described manufacturer’s case IV inotrope: 70% registry 280/309 NYHA class IV: 100% 90-DAY IN-HOSPITAL MORTALITY, n=60 (27%) Presumably complete follow-up of in-hospital (91%) CAUSES deaths Sepsis - 33% Multiorgan failure - 20% Wide confidence intervals on predicted Right heart failure - 14% probabilities, calibration questionable, and Respiratory failure - 7% predictions not validated Technical difficulties - 5% Device failure - 5% No assessment of whether or how much use Hemorrhage - 3% of variables could improve patient selection or Stroke - 3% outcomes; thresholds of acceptable operative Several other causes - 10% risk not defined INDEPENDENT CORRELATES (OR = odds ratio) Platelet count < 148,000; OR = 7.7 Serum albumin < 3.3 g/dl; OR = 5.7 INR > 1.1; OR = 5.4 Vasodilator; OR = 5.2 Mean pulmonary artery pressure < 25 mmHg; OR = 4.1 Aspartate aminotransferase > 45 U/ml; OR = 2.6 Hematocrit < 34%; OR = 3.0 Blood urea nitrogen > 51 U/dl; OR = 2.9 No IV inotrope; OR = 2.9 39 Use of Left Ventricular Assist Devices as Destination Therapy in End-Stage Congestive Heart Failure: A Systematic Review Evidence-based Synthesis Program Study/Country/ Inclusion/Exclusion Funding Sample of Patients Outcomes & Baseline Correlates Study Quality Criteria Source Leitz 200711 See above See above RISK SCORE See above C-statistic 0.89 Continued RISK SCORE CATEGORIES % PREDICTED (CI) vs OBS 0 to 8 (n=65) 2 (1 to 5) vs 6 9 to 16 (n=111) 12 (8 to 18) vs 14 17 to 19 (n=28) 44 (33 to 56) vs 61 >19 (n=18) 81 (66 to 91) vs 82 Adamson Inclusion Criteria n=55 subgrouped into < 70 (n= Patients eligible for destination therapy, 201134 Patients enrolled 25) and ≥ 70 years old (n=30) < 70 ≥70 received HeartMate II in clinical trials of group group Single center in the HeartMate II Male: not reported Age determined before implantation surgery U.S. ventricular assist NYHA class IV: 100% MEAN AGE (years) 57 76 and likely valid device Mean LVEF: 20% MEDIAN DURATION WITH DEVICE (days) Funding IV inotrope: 64% 415 482 Presumably complete follow-up in trials Source: not All carefully screened Intra-aortic balloon pump: 5% DROPOUTS 3 0 reported using criteria of Defibrillator: 74% SURVIVAL (p=0.81) No confidence intervals on differences clinical trials and CMS Cardiac resynchronization 30 days 96% 97% between small age subgroups therapy: 51% 6 months 88% 83% Mean Destination Therapy Risk 12 months 72% 75% No adjustment for preoperative differences Score: 9.3 AT 6 MONTHS NYHA CLASS I or II 100% 89% p=0.35 MEAN 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% INTERMACS – Interagency Registry for Mechanically Assisted Circulatory Support, LVEF – left ventricular ejection fraction, IV – intravenous, NYHA – New York Heart Association, HR – hazard ratio, OR – odds ratio, INR – international normalization ratio, CI – 95% confidence interval, OBS – observed, BUN – blood urea nitrogen, MLHFQ – Minnesota Living with Heart Failure Score, KCCQ – Kansas City Cardiomyopathy Questionnaire 40.