Background: Among social media (SoMe) platforms, Twitter and YouTube have gained popularity, facilitating communication between cardiovascular professionals and patients.Objective: This mixed-methods systematic review aimed to assess the source profile and content of Twitter and YouTube posts about heart failure (HF). Methods: We searched PubMed, Embase and Medline using the terms “cardiology,” “social media,” and “heart failure”. We included full-text manuscripts published between January 1, 1999, and April 14, 2019. We searched Twitter and YouTube for posts using the hashtags “#heartfailure”, “#HF”, or “#CHF” on May 15, 2019 and July 6, 2019. We performed a descriptive analysis of the data. Results: Three publications met inclusion criteria, providing 677 tweets for source profile analysis; institutions (54.8%), health professionals (26.6%), and patients (19.4%) were the most common source profiles. The publications provided 1,194 tweets for content analysis: 83.3% were on education for professionals; 33.7% were on patient empowerment; and 22.3% were on research promotion. Our search on Twitter and YouTube generated 2,252 tweets and > 400 videos, of which we analyzed 260 tweets and 260 videos. Sources included institutions (53.5% Twitter, 64.2% You- Tube), health professionals (42.3%, 28.5%), and patients (4.2%, 7.3%). Content included education for professionals (39.2% Twitter, 62.3% YouTube), patient empowerment (20.4%, 21.9%), research promotion (28.8%, 13.1%), professional advocacy (5.8%, 2.7%), and research collaboration (5.8%, 0%). Conclusion: Twitter and YouTube are platforms for knowledge translation in HF, with contributions from institutions, health professionals, and less commonly, from patients. Both focus largely on education for professionals and less commonly on patient empowerment. Twitter includes more research promotion, research collaboration, and professional advocacy than YouTube.