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Diastolic dysfunction is linked to the initiation and progression of aortic stenosis: a hypothesis

Partho P Sengupta1, Naveena Yanamala1,2, Phillipe Pibarot3

  • 1Division of Cardiovascular Diseases and Hypertension, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.

European Heart Journal
|June 23, 2026
PubMed

Insights

Artificial intelligence challenges traditional views of aortic stenosis (AS). Diastolic dysfunction may indicate an early, shared cause of AS and heart remodeling, not just a consequence.

Area of Science:

  • Cardiology
  • Biomedical Engineering
  • Artificial Intelligence in Medicine

Background:

  • The traditional view of aortic stenosis (AS) links progressive valvular obstruction to increased afterload, causing left ventricular remodeling and dysfunction.
  • Emerging artificial intelligence (AI)-based data suggest a different sequence, challenging the established understanding of AS pathophysiology.
  • Diastolic dysfunction has been observed to predict future AS, even in individuals without significant valve imaging findings, indicating a potential upstream factor.

Purpose of the Study:

  • To propose a new hypothesis for the pathophysiology of calcific aortic stenosis (AS).
  • To challenge the conventional causal hierarchy in AS development.
  • To suggest a framework for earlier risk assessment in AS using AI-based phenotyping.

Main Methods:

  • Utilizing AI-based observational data to analyze patterns in cardiovascular health.
  • Integrating biomechanical principles and inflammatory markers into a hypothetical model.
  • Examining the relationship between diastolic dysfunction, arterial stiffness, and ventriculo-valvular-vascular coupling.

Main Results:

  • AI-derived risk scores for diastolic dysfunction can predict future AS, independent of traditional valve imaging.
  • Diastolic dysfunction may serve as an early indicator of a shared upstream pathophysiological state, rather than solely a downstream consequence of AS.
  • This state involves a mechano-inflammatory milieu characterized by arterial stiffness and disrupted coupling.

Conclusions:

  • Diastolic dysfunction is hypothesized to be an early marker of a shared mechano-inflammatory process contributing to AS and myocardial remodeling.
  • This perspective shifts the understanding from a linear causal chain to a more complex interplay of factors.
  • The proposed framework, integrating AI, biomechanics, and inflammation, offers a novel approach to early risk stratification for calcific AS.

Keywords:
Aortic SclerosisAortic StenosisArtificial intelligenceDiastolic Dysfunction

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