Table 1.

Top 5 clinical and guideline development takeaways from recent heart failure guidelines

	Takeaways for heart failure management	Takeaways for guideline development
1.	•For HFrEF, there is universal agreement to initiate quadruple therapy as soon as possible, but the best sequencing strategy remains elusive.	•In the absence of comparative RCTs, model-based estimates of the benefits of different HFrEF sequencing strategies could inform future guideline recommendations.
2.	•For HFimpEF, the ESC and AHA/ACC/HFSA guidelines recommend against withdrawing HFrEF pharmacotherapy, based on trial results published after the 2017 CCS guidelines.	•Guideline recommendations and discussions may not incorporate the latest evidence on a topic (at least until a subsequent update). Systematic update efforts are necessary to ensure clinicians are informed as new evidence emerges.
3.	•For HFpEF, the certainty of evidence for pharmacotherapy is low at best (except for SGLT2i initiation), resulting in guideline discordance. •This is an opportunity for clinicians to engage patients with HFpEF in shared decision-making, using decision aids and patient-oriented outcome data.	•Recommendations should be accompanied by sufficient information on treatment benefits and harms to empower clinicians to engage patients in shared decision-making.
4.	•For HFmrEF, differences between guidelines are attributable to the rapid pace of evidence advancement (with the AHA/ACC/HFSA being the most up to date). •The ESC and AHA/ACC/HFSA make weak recommendations in favour of ARB/ARNI, beta-blockers, and MRAs. •The AHA/ACC/HFSA also makes a moderate-strength recommendation in favour of SGLT2i’s.	•The GRADE certainty-of-evidence rating system provides greater transparency and allows for more-nuanced interpretations than the traditional ACC/AHA levels of evidence.
5.	•There are unanimous recommendations for intravenous iron in the treatment of iron deficiency with HFrEF. •The clinical benefits of sodium restriction are unclear. In SODIUM-HF (published after all 3 guidelines),9 strict sodium restriction did not lead to fewer HF events, compared to usual care (∼2 g/d).	•Intravenous iron for patients with iron deficiency and HFrEF has the greatest impact on quality of life of any HFrEF pharmacotherapy, a priority for patients with HFrEF.10 Future guideline iterations should feature this therapy more prominently. •Incorporation of emerging evidence on the preferences and values of patients with HFrEF may further guide the prioritization of interventions. •In the absence of evidence comparing the efficacy of different sodium targets, nuanced weak recommendations based on reasonable ranges may still be possible (eg, sodium intake target of ∼1.4–3 g/d). When this is not feasible, it is valuable to strongly recommend shared decision-making informed by transparent disclosure of the uncertainty regarding potential benefits and harms.

ACC, American College of Cardiology; AHA, American Heart Association; ARB, angiotensin receptor blocker; ARNI, angiotensin receptor-neprilysin inhibitor; CCS, Canadian Cardiovascular Society; EF, ejection fraction; ESC, European Society of Cardiology; GRADE, Grading of Recommendations, Assessment, Development and Evaluations; HF, heart failure; HFimpEF, HF with improved EF; HFmrEF, HF with mildly reduced EF; HFpEF, HF with preserved EF; HFrEF, HF with reduced EF; HFSA, Heart Failure Society of America; MRA, mineralocorticoid receptor antagonist; RCT, randomized controlled trial; SGLT2i, sodium/glucose cotransporter-2 inhibitor; SODIUM-HF, Study Of Dietary Intervention Under 100 mmol in Heart Failure trial.