More Than Survival: Futility Suzanne V. Arnold, MD, MHA Saint Luke’s Mid America Heart Institute/UMKC March 12, 2016

Defining Futility When risks do not outweigh expected benefits Risk of a poor outcome is too high Treatment fails to achieve its designed benefits Prolonged survival with reasonable quality of life Improve heart failure symptoms without substantial other adverse side effects

Definition of Poor Outcome Assessed at 1 year after LVAD Death Very poor heart failure-specific quality of life KCCQ <45 over the year following LVAD Missing from the definition: Cognitive function Stroke Generic quality of life Arnold et al., Circ Cardiovasc Qual Outcomes. 2013 Sep 1;6(5):591-7. Arnold et al., Circulation. 2014 Jun 24;129(25):2682-90.

Rate of Poor Outcome at 1 Year After DT-LVAD: 30% VAD Patients v3.0 in INTERMACS May 2012-Sept 2013 N=3922 –2208 BTT/possible BTT –45 BTR, rescue, other –31 BiVAD –151 missing all comorbidity data Analytic Cohort N=1487 Died <1 year N=336 (23%) Survived N=1151 –177 No KCCQ follow-up Rate of Poor Outcome at 1 Year After DT-LVAD: 30% Follow-up KCCQ data N=974 Very Poor QoL N=94 (7%) Acceptable QoL N=880 (70%)

Methods Multivariable logistic model was built to predict a poor outcome at 1 year after DT-LVAD 18 baseline demographic and clinical variables Parameter estimates penalized to minimize the effect of over-fitting Inverse propensity weighting was used to adjust for loss to follow-up Multiple imputation for missing data was performed via sequential regression modeling

Model OR (95% CI) P-value Age (per +10 years) 1.23 (1.08-1.40) 0.002 KCCQ-12 Summary Score (per -10 pts) 1.10 (1.02-1.18) 0.010 BMI (per +5 kg/m2) 1.12 (1.02-1.24) 0.017 INTERMACS Patient Profile 1-2 1.27 (0.97-1.65) 0.078 History of solid organ cancer 1.39 (0.96-2.01) 0.079 Previous cardiac operation 1.23 (0.95-1.59) 0.119 Hemoglobin (per +1 g/dL) 0.95 (0.89-1.02) 0.170 History of illicit drug use/alcohol abuse 1.29 (0.88-1.89) 0.189 Non-significant factors: sex, diabetes, stroke, PAD, creatinine, lung disease, albumin, arrhythmias, tricuspid regurgitation, KCCQ missing 0 1 2 3

Model Performance Discrimination: C-index=0.64, Validated=0.62 Calibration: Slope=1.01, Intercept=0.01

Outcomes by Predicted Risk

When is an LVAD futile? Expected benefits > potential harm Is there a predicted risk of poor outcome that is sufficiently high to claim futility?

Outcomes by Predicted Risk 10% of population While nearly 1/3 of patients have poor outcomes over the year after DT-LVAD, identifying patients at such a high-risk of this poor outcome to deem the LVAD futile is unlikely

When is an LVAD futile? Expected benefits > potential harm Is there a predicted risk of medical management sufficiently low to claim futility?

Outcomes by Predicted Risk of Poor Outcome with Medical Therapy EVEREST Risk Score N (%) Predicted Risk with Meds (6m) 1-Year Outcome with LVAD Low 80 (6.1%) 12.9% 19.6% Moderate 185 (14.1%) 25.2% 31.4% High 67 (5.1%) 37.8% 24.3% Not calculated 978 (74.7%) - 31.6% Allen LA et al., Circ Cardiovasc Qual Outcomes. 2011 Jul;4(4):389-98.

When is an LVAD futile? Patient perspective: Societal perspective: Standards uncertain and may vary across patients Societal perspective: Much longer survival after LVAD Consider using risk models and engage in shared decision-making

Thank you