Volume 449, 15 April 2026, 134196Author links open overlay panelAnna Cantone a, Matteo Serenelli a, Aldostefano Porcari b c dShow moreIntroduction

Aortic valve stenosis (AS) in older adults is increasingly managed as a procedural condition: define disease severity, replace the valve, and predict clinical recovery [1]. Yet, in a substantial proportion of patients, the myocardium tells a different story. Transthyretin amyloid cardiomyopathy (ATTR-CM) frequently coexists with AS, affecting hemodynamics, symptom burden and long-term outcomes [2]. Both conditions are strongly age-dependent, and their association is now recognized as more than coincidental. The critical question is no longer whether this dual pathology exists, but whether it is being systematically identified and managed with the same clarity and therapeutic intent routinely applied to the valve [3].

In this issue of the International Journal of Cardiology, Patel and colleagues [4] report the long-term outcomes of patients with AS with and without concomitant ATTR-CM (AS-CA) in a prospective, multicenter observational study. The authors are to be commended for addressing a clinically relevant question with sufficient follow-up to capture ATTR-CM-driven outcomes. Their findings challenge the common assumption that the prognostic benefit of a successful valve replacement remains durable when the myocardium is infiltrated by amyloid; an assumption largely derived from earlier studies reporting comparable early and mid-term mortality between lone AS and AS-CA [3].

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Access through your organizationSection snippetsAS and ATTR-CM: a distinct phenotype with prognostic relevance

The study included 406 elderly (median age 84 years) patients referred for potential aortic valve replacement (AVR), across three European centers, all systematically screened with bone scintigraphy to differentiate lone AS from AS-CA. Decision to perform an AVR (transcatheter or surgical) was made by heart teams blinded to scintigraphy results, minimizing treatment allocation bias. AS-CA was identified in 11.6% of the cohort (all attributed to ATTR-CM), confirming that dual pathology is far

Therapeutic implications

Patients with severe AS have been systematically excluded from pivotal amyloid trials, leaving this dual-pathology population without high-quality evidence to guide post-AVR management [5].

In the present study, fewer than 15% of patients received tafamidis during follow-up, a proportion that does not reflect current practice where treatment is typically initiated promptly once AS-ATTR-CM is diagnosed and has demonstrated benefit [6], [7]. In this largely untreated AS-CA population, 1-year

Methodological considerations: what the data do and do not prove

The study has limitations. First, monoclonal protein testing was not systematically performed before scintigraphy, raising the possibility that some patients with AL amyloidosis and Perugini grade 0 uptake may have been misclassified as lone AS. Second, TTR genetic testing was performed only in patients ultimately diagnosed with ATTR-CM, unsurprisingly resulting in exclusive identification of wild-type disease; patients with TTR variants associated to low tracer sensitivity may have gone

Conclusions

The message emerging from the study by Patel and colleagues is clear: in AS-CA, the myocardium continues to matter long after the valve has been replaced. Treating AS-CA as a purely procedural disease risks overlooking a progressive myocardial process that continues to drive HF events, frailty, and late mortality despite technically successful valve intervention. Recognizing and treating AS and ATTR-CM is central to inform and improve prognosis, guide follow-up intensity, and identify patients

CRediT authorship contribution statement

Anna Cantone: Conceptualization, Writing – original draft. Matteo Serenelli: Conceptualization, Writing – review & editing. Aldostefano Porcari: Conceptualization, Validation, Writing – original draft, Writing – review & editing.

Funding

None.

Declaration of competing interest

The authors have nothing to disclose for the content of this manuscript. Outside the submitted work: Aldostefano Porcari has received fees for education activities from Alnylam and Pfizer, honoraria and consulting income from Bayer.

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