Managing Concomitant Aortic Stenosis and Transthyretin Cardiac Amyloidosis: Evolving Care Strategies

Dr. Maeusli:

You’re listening to ReachMD, and this is an AudioAbstract. I’m Dr. Mimi Maeusli, and today, I’ll be talking about findings published in the European Heart Journal in June 2025. This multinational study looked at the prognostic impact of amyloid-specific therapy in patients with concomitant aortic stenosis and transthyretin-, or ATTR-, associated cardiac amyloidosis.

This dual pathology is increasingly recognized in elderly patients and can contribute to structural heart failure. We already know that aortic valve replacement, or AVR, can help improve outcomes in this population. But what hasn’t been well understood is whether adding ATTR-specific treatment can further improve survival.

The study included 226 patients with moderate or severe aortic stenosis and confirmed ATTR-associated cardiac amyloidosis, enrolled across 16 centers in 10 countries. Nearly all patients—99 percent—had wild-type ATTR amyloidosis.

So what did they find? Over a mean follow-up of 3.6 years, ATTR-specific medication, primarily tafamidis, was associated with a 60 percent reduction in all-cause mortality and about a 50 percent reduction in cardiovascular death compared to those who didn’t receive ATTR treatment. These benefits remained significant after statistical adjustment for age, surgical risk, aortic stenosis severity, and other clinical covariates.

However, ATTR-specific medication was not associated with a reduced risk in hospitalization for heart failure, perhaps due to competing risks as patients without ATTR treatment experienced higher rates of death.

Additionally, AVR alone reduced all-cause mortality by about 40 percent. But importantly, the most favorable outcomes were seen in patients who received both AVR and ATTR-specific medication. In fact, their survival was comparable to that of patients with isolated aortic stenosis who underwent AVR.

Another noteworthy finding was that only about one-third of patients actually received tafamidis. The reasons? Limited access, reimbursement barriers, and clinical hesitation, especially in patients with more advanced New York Heart Association classifications.

Of course, we should acknowledge this was not a randomized trial, and there may have been selection bias. For instance, patients who received ATTR-specific medications were younger. The interval between AVR and starting ATTR treatment also varied and may have influenced outcomes, though this factor was not associated with mortality. And because heart failure hospitalizations were reported by individual sites, there may have been differences in how those events were classified.

Nevertheless, ATTR-specific treatment may offer a survival benefit in patients with concomitant aortic stenosis and ATTR-associated cardiac amyloidosis—beyond what AVR alone can achieve. The authors emphasize the need to identify cardiac amyloidosis in this population and to treat eligible patients with potentially life-prolonging therapy.

This has been an AudioAbstract, and I’m Dr. Mimi Maeusli. To access this and other episodes in our series, visit ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!

Reference
Nitsche C, Dobner S, Rosenblum HR, et al. Cardiac transthyretin amyloidosis treatment improves outcomes after aortic valve replacement for severe stenosis. Eur Heart J. 2025;46(44):4795-4806. doi:10.1093/eurheartj/ehaf362