Heart failure is a complex disease and whilst clinical practice guidelines posit the “four pillars” as the cornerstone of effective medical management, the very nature of heart failure means that most patients have multiple comorbidities that also need to be addressed. This month, we welcome Biykem Bozkurt – the Mary and Gordon Cain Chair and Professor of medicine at Baylor College of Medicine, Texas – a true pioneer in translational research and a lead contributor to clinical practice guidelines, including the 2022 AHA/ACC/HFSA guidelines. There is perhaps no better guest to ask some of the most challenging questions around implementing guideline directed medical therapy (GDMT): reviewing GDMT in valvular heart disease patients; initiating GDMT whilst addressing non-cardiac comorbidities; to where medical treatment is evolving, beyond the central dogma of the “four pillars”. All of this and more are covered in this fascinating and insightful discussion. Questions can be sent via Twitter to our host @mvaduganathan or to @radcliffeCARDIO. This podcast is supported by an unrestricted educational grant from AstraZeneca.