Heart failure (HF) has conventionally been defined as the inability of the heart to pump sufficiently to meet the needs of the body for oxygen. In addition to HF with reduced ejection fraction (HFrEF), nearly half of patients who present with HF signs and symptoms have preserved ejection fraction (HFpEF). HFrEF presentation includes reduced contractile function and dilation of the left ventricle (LV), while HFpEF presentation includes abnormal LV relaxation and diastolic stiffness. Both HF types have similar hospitalization, morbidity, and mortality rates, and medications that improve outcomes for patients with HFrEF do not show similar benefit to patients with HFpEF. Understanding the cell signaling pathways and molecular mechanisms that trigger HF is a major challenge in cardiovascular medicine. Our conference is conceptually framed around the hypothesis that while HFrEF and HFpEF clearly have distinct etiologies and driving mechanisms, they may share modifiable pathways and biological mediators in common. The convergence among cells involved in inflammation and extracellular matrix deposition will be a major theme. The meeting program includes specific focus on cell heterogeneity, cell-cell cross-talk, individual cell responses, cardiac interactions with other organs, cardiometabolic aspects of all cell types, and approaches to identify new pharma targets. Scientific Relevance: There is a strong need to better understand the cellular and molecular mechanisms of heart failure development. Gaps: 1. Clarify concepts of cardiac remodeling, inflammation, fibrosis, and cell heterogeneity. 2. Develop standard procedures for rigorous assessments. 3. Examine exacerbation of HF development in the setting of co-morbidities. 4. Harness knowledge from other research arenas to develop new strategies to combat HF. 5. Define the use of animal models for optimal use in HF research. 6. Define phenotypes that distinguish subtypes of heart failure (HF): HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Specific Aims: 1. to disseminate and share new knowledge about heart failure, focused on cell and molecular signaling that yields HF; 2. to focus on controversies and knowledge gaps that prevent or limit therapeutic translation; and 3. to promote the educational growth and careers of young scientists. Anticipated outcomes: 1. Attendees will leave this meeting with clear ideas on the most critical experiments needed to accelerate the field forward. 2. There will be a better understanding of the methods that can be applied to better translate basic science to clinical use. 3. Trainees will understand how to advance their careers in the heart failure field. 4. Scientific knowledge and clinical practice will be advanced in that we will have a comprehensive evaluation of the current state of understanding of heart failure and better understand the challenges that remain before we can more completely translate the dynamics of cellular interactions in heart failure. Innovation: We know of no other conference that focuses on the cellular components of heart failure. We will challenge current concepts and fill in the knowledge gaps to help propel the field forward. Bringing together interdisciplinary groups of investigators will ample provide opportunity for cross-fertilization. In particular, we will use approaches in proteomics and big data science to seek paradigm shifts in research strategies.