question: Purpose: Gene expression profiling (GEP) and donor-derived cell-free DNA (dd-cfDNA) provide effective non-invasive rejection surveillance for heart transplant (HT) recipients with a trend toward improved quality of life. During the COVID-19 pandemic, rejection monitoring and titration of mediations in HT patients was difficult due to limited health-care resources for endomyocardial biopsy (EMBx). This is the first Canadian study to assess non-invasive rejection surveillance in improving patient satisfaction and reducing anxiety during HT rejection screening. Methods: Adult HT recipients, at least 6 months post-transplant, were enrolled to have surveillance EMBx replaced by non-invasive rejection testing with GEP and dd-cfDNA. Patients with multiorgan transplant, dialysis, or high rejection risk (recent acute cellular rejection ≥ grade 2R, new graft dysfunction, or heart failure) were excluded. All patients completed the Medical Outcomes Study 12-item Short Form Health Survey (SF-12) and a patient satisfaction survey. Thematic analysis was performed for open-ended responses. Results: Out of 90 patients screened, 31 had their routine EMBx replaced by non-invasive rejection testing. Based on test results, 89% of EMBx were safely eliminated. On the SF-12, participants had a median physical health score of 43 (40-53) and mental health score of 53 (46-58) out of 100. Patients’ self-reported satisfaction was 90%. Median self-reported anxiety score prior to EMBx was 50 (10-71) versus 2.5 (0-7.5) out of 100 prior to GEP/dd-cfDNA. Four codes (“emotions” (pain, anxiety, fear), “time”, “biopsy”, “accuracy”) were used to uncover two themes of “Superiority to Biopsy” and “Mental or Physical Stress”. Patients described feeling much more satisfied and less emotionally distressed with the non-invasive screening compared to EMBx. HT patients reported less fear and anxiety, reduced pain, and enjoyed the simplicity of non-invasive testing. Conclusion: Non-invasive rejection surveillance screening can positively impact patients’ mental health. In this study, non-invasive rejection surveillance eliminated the recovery time and risk of an invasive procedure for HT recipients while reducing anxiety, improving patient satisfaction, and providing an alternative way to screen patients during a period of limited resources due to a global pandemic.