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Competing Interests: Disclosures Angela Velleca None Michael A Shullo Consulting- Natera Kumud Dhital None Estela Azeka MD None Monica Colvin MD Grants- Natera-Grant funding; Advisory board- Natera; Consulting- Mescape Eugene DePasquale Grants- CareDX; Advisory Board- Yale Marta Farrero Speakers bureaus- Novatris, AstraZeneca, Boehringer, Chiesi; Meeting support- Novartis, Chiesi; Material support/ Other Services- AstraZeneca Luis García-Guereta None Gina Jamero None Kiran Khush Grants- National Institutes of Health, Enduring Hearts; Royalties- Stanford; Consulting, speakers bureaus- CareDx Jacob Lavee None Stephanie Pouch None Jignesh Patel Grants- Alexion; Consulting- CareDx, Natera; Advisory Board- CareDx, Natera; CJ Michaud None Stephan Schubert Consulting- Medtronic, Edwards; Speakers Bureaus- Abbott, Lifetech, Medtronic; Meeting support- Medtronic, Edwards Annalisa Angelini None Lilibeth Carlos None Sonia Mirabet None Michael Pham Grants- CareDx, Royalties-Up to Date Simon Urschel Grants- Canadian Institute for Health Research, Enduring Hearts, Heart and Stroke foundation; Speaker/Educational- University of Alabama; Meeting support- Lange Symposium; Advisory Board- SMB of the Canadian Donation and Transplantation Research Program Kyung-Hee Kim None Shelly Miyamoto None Sharon Chih Grants- Heart and Stroke Foundation Ontario, Canadian Institutes of Health Research Kevin Daly Grants- US Department of Defense, Novartis, AHA/Enduring Hearts, Consulting- AstraZeneca; Advisory Board- CareDx Paolo Grossi Consulting- Merck, Sharp & Dohme Allovir, Takeda; Speakers Bureaus- Atara, Gilead, Shionogi; Advisory Board- Reithera Doug Jennings None In-cheol Kim None Hoong Sern Lim Speakers bureaus- Abiomed Tara Miller None Luciano Potena Consulting- Biotest, Novartis; Speakers bureaus- Biotest, Takada, Paragonix, Boeringher Ingheleim, AstraZeneca Howard Eisen None Lavanya Bellumkonda Grants- Natera, CareDx; Meeting support- Conformal Medical; Advisory Board- CareDx Lara Danziger-Isakov Grants- NIH, Ansun BioPharma, Astellas, Merck, Pfizer, Takada, AiCuris; Consulting- Takeda; Speakers Bureaus- RMEI; Meeting support- ID SAFE: Swiss Infectious Disease; Advisory Board/DSMB- Merck Fabienne Dobbels None Michelle Harkess None Daniel Kim None Haifa Lyster None Yael Peled None Zdenka Reinhardt None

Background: The aim of this study was to identify whether the addition of cognitive impairment, depression, or both, to the assessment of physical frailty provides better outcome prediction in patients with advanced heart failure referred for heart transplantation (HT)., Methods: Beginning in March 2013, all patients with advanced heart failure referred to our Transplant Unit have undergone a physical frailty assessment using the Fried frailty phenotype. Cognition was assessed with the Montreal Cognitive Assessment and depression with the Depression in Medical Illness questionnaire. We assessed the value of 4 composite frailty measures: physical frailty (PF ≥ 3 of 5 = frailty), "cognitive frailty" (CogF ≥ 3 of 6 = frail), "depressive frailty" (DepF ≥ 3 of 6 = frail), and "cognitive-depressive frailty" (ComF ≥ 3 of 7 = frail) in predicting outcomes., Results: Frailty was assessed in 156 patients (109 men, 47 women), aged 53 ± 13 years, and with a left ventricular ejection fraction of 27% ± 14%. Inclusion of cognitive impairment or depression in the definition of frailty increased the proportion classified as frail from 33% using PF to 42% using ComF. During follow-up, 28 patients died before ventricular assist device implantation or HT. Frailty was associated with significantly lower ventricular assist device- and HT-free survival, with CogF best capturing early mortality: 12-month survival for non-frail and frail cohorts was 81% ± 5% vs 58% ± 10% (p < 0.02) using PF and 85% ± 5% vs 56% ± 9% (p < 0.002) using CogF. Combining the Depression in Medical Illness score with PF or CogF did not strengthen the relationship between frailty and mortality., Conclusions: The addition of cognitive impairment to the assessment of PF strengthened its capacity to identify advanced heart failure patients referred for HT who are at high risk of early death., (Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)