Heart Failure Mechanisms,Therapy and Outcomes: What We Are Still Getting Wrong

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Published Jun 25, 2026

Dr Milton Packer (Baylor University Medical Center, Dallas, TX, US) joins us for a wide-ranging discussion on the conceptual foundations of heart failure, challenging several long-held assumptions about its mechanisms, classification and therapeutic targets, and considering what the field may still be getting wrong.

In this interview, Dr Packer sets out why he believes some core ideas in heart failure are flawed, and why those misconceptions carry real clinical consequences. He examines the case for understanding heart failure with preserved ejection fraction (HFpEF) as a systemic, adipose-driven condition, and what such a framework would mean for how clinicians phenotype patients and how future trials are designed. He also considers whether the emerging data on GLP-1 receptor agonists and obesity-focused therapies confirm an adipose-centric model, or whether the field risks moving towards that conclusion prematurely.

Interview Questions:

You've argued that some core ideas in heart failure are flawed — what do you think we're getting most wrong, and why does it matter clinically?
If HFpEF were fully viewed as a systemic, adipose-driven condition, how should that change the way we phenotype patients or design trials?
With emerging data on GLP-1 and obesity-focused therapies, do you see this as confirming an adipose-centric model, or are we moving too quickly to that conclusion?
We still rely heavily on ejection fraction and acute/chronic labels — what would you move away from, and what would you use instead?
Despite increasingly complex trials, outcomes remain limited — what do you think is holding us back in trial design or regulation?
Looking 10–15 years ahead, what current heart failure approach or idea do you think we might look back on as a mistake?

Editors: Jordan Rance
Videographer: Tom Green, David Ben-Harosh
Support: This is an independent interview produced by Radcliffe Cardiology.

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