These targets include not only those modulated by the recommended treatments in this document, but also emerging treatments. For example, vericiguat, a soluble guanylyl cyclase stimulator, has demonstrated bene t for the combined outcome of death from CV causes or rst hospitalization for HF (150). The large and growing target and therapy list in HFrEF signi cantly complicates HF management for both patients and their care teams. However, several guiding principles can improve decision-making for and adherence to GDMT, which, in turn, is likely to improve patient outcomes. Principle 1: GDMT is the foundation of HF care, and the GDMT with the highest expected bene t should be prioritized. Based on large randomized trials for HFrEF, ARNIs, evidence-based beta-blockers, aldosterone antag- onists, and SGLT2 inhibitors are rst-line medications for all populations. HYD/ISDN is also a rst-line medication for self-identi ed African Americans. Ivabradine is a second-line medication for select populations. Principle 2: Target doses are associated with best outcomes. Attempt to achieve target doses of all recom- mended therapies in the absence of contraindications and/or intolerance. Titration should occur even if the patient appears stable or their symptoms and/or EF improve. Principle 3: Start GDMT immediately. Delayed initia- tion of GDMT is associated with never initiating GDMT (151). Principle 4: Attention to the clinical, social, and nancial barriers to achieving GDMT should be priori- tized. Multidisciplinary care should be targeted to the individual patient s barriers. Consider early referral to an HF team for assistance. Principle 5: Diligent management of volume status will reduce patient symptoms. Congestion drives symp- toms and hospitalizations. If the volume status is unclear, consider performing right heart catheterization and/or referral to an HF specialist. 