Abstract Background The efficacy of digital programs to improve the management of chronic heart failure (CHF) and chronic kidney disease (CKD) is not established. Building on related studies in digital health, behavioural counselling, and social support, we evaluated whether an automated digital counselling program with social network support (ODYSSEE-vCHAT) could improve mental health and health-related quality of life in patients with CHF or CKD. Purpose The primary objective was to examine whether engagement with ODYSSEE-vCHAT was associated with a minimal clinically important difference for improvement in the Mental Component Summary (MCS) of the SF-36 at end-of-study. Secondary outcomes included: ENRICHD Social Support Index (ESSI), Patient Health Questionnaire for Depression (PHQ-9) Godin-Shephard Leisure Time Physical Activity Scale (GSLTPAQ), and an index of the frequency to which patients engaged in goal-directed activities for living well (EUROIA). Methods ODYSSEE-vCHAT was a multi-centre, single group, open label study with assessments at baseline and end-of-study (approximately 11 months). Inclusion criteria were: ≥18 years of age, diagnosis of CHF (reduced ejection fraction (EF) ≤ 40%, mid-range EF, 41-49%, or preserved EF ≥ 50%); or CKD diagnosis (>10% risk for dialysis using the 4-variable, 2-year Kidney Failure Risk Equation, or on dialysis). Exclusion was based on inability to participate due to co-morbidities. The digital counselling protocol taught self-care skills to improve mental health, quality of life, and adherence to medications, exercise, diet, and smoke-free living (Figure 1). Patient engagement with ODYSSEE-vCHAT was defined as Not Engaged (0 logon minutes) vs. Engaged (> 0 logon minutes). The primary outcome was a minimal clinically important difference for MCS change: ΔMCS ≥ 3.8 or MCS ≥ 65 at baseline and study endpoint. It was assessed using multivariable binary logistic regression, controlling for exposure to COVID-19 and health literacy. Secondary outcomes were assessed using multivariable linear regression analyses with the same covariates. Results 215 patients were enrolled. There were 7 deaths and 34 withdrew. In our sample of 174 patients, mean age = 54.4 years (95% Confidence Interval, CI, 25, 81), gender identity as women, n = 68 (39%), ethno-racial group other than White, n = 83, (48%), primary diagnosis, CHF, n = 68 (39%), and CKD, n = 106 (61%). Duration of enrolment to end-of-study: median = 352 days, (95% CI, 159, 496). Engagement with ODYSSEE was associated with therapeutic change on the MCS (for both CHF and CKD patients, and CHF patients alone), GSLTPAQ, and EUROIA, but not the PHQ9 or ESSI (Figure 2). Conclusions Automated digital counselling with social network support promotes improvement in indices of mental health for patients with CHF and CKD. These findings support a follow-up randomized controlled trial.Figure 1.ODYSSEE-vCHAT Study ProtocolFiFigure 2.ODYSSEE-vCHAT Study Outcomes