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Carlos Henrique Del Carlo: HFpEF Reimagined as an Adipose Tissue Driven Disease

Carlos Henrique Del Carlo and Marwan Refaat

Apr 14, 2026, 15:07

Carlos Henrique Del Carlo: HFpEF Reimagined as an Adipose Tissue Driven Disease

Carlos Henrique Del Carlo, Collaborating Professor at University of São Paulo Medical School, shared a post on LinkedIn:

”HFpEF: Does it start in the Heart — or in the Adipose Tissue?

The traditional heart failure model focuses predominantly on the myocardium. However, the ‘Adipokine Hypothesis,’ recently proposed by Milton Packer (JACC 2025), suggests a radical paradigm shift: HFpEF may actually be the cardiac manifestation of systemic visceral adipose tissue dysfunction.

In this framework, adipose tissue is not merely an energy reservoir; it is an active endocrine organ that dictates cardiovascular biology.

The Proposed Pathophysiological Cascade:

Visceral Adiposity: Expansion and dysfunctional transformation of adipose tissue (adipopathy).
Adipokine Imbalance: A decline in cardioprotective molecules (Domain I) and a surge in pro-inflammatory and anti-natriuretic signals (Domain III).
Systemic Inflammation: Microvascular oxidative stress and reduced nitric oxide bioavailability.
Sodium Retention: Plasma volume expansion mediated by adipose biology, occurring even before overt cardiac failure.
Myocardial Fibrosis: The heart as the “end-organ” target of a systemic insult that began in the periphery.

Why does this change our practice?

It explains why the most impactful therapies today – such as SGLT2 inhibitors and GLP-1 receptor agonists – are so effective: they target the metabolic and inflammatory substrate, not just cardiac mechanics.

When treating HFpEF, we are no longer just managing congestion; we are attempting to modulate the biological drivers of the disease.

Question for debate: Do you believe that, in the future, HFpEF management will be guided primarily by the biology of inflammation and adipose tissue, rather than just hemodynamics?

Reference: Packer M. The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction. J Am Coll Cardiol. 2025;86(16):1 801-1815.

Check the infographic below (produced with NotebooLM) for a visual summary of the adipokine hypothesis of HFpEF.”

Marwan Refaat Tenured Professor of Medicine, Biochemistry and Molecular Genetics at the American University of Beirut, shared this post on Linkedin, adding:

”Cardiovascular-kidney-metabolic (CKM) syndrome HFpEF Metabolic-Obese phenotype Visceral adiposity Systemic inflammation Microvascular dysfunction.”

Carlos Henrique Del Carlo: HFpEF Reimagined as an Adipose Tissue Driven Disease