Heart Device Fails to Improve Longevity in New Amyloidosis Research

For patients with transthyretin cardiac amyloidosis (TTR-CA), the implantable cardioverter-defibrillator (ICD) may not be delivering on its promise of providing life-saving health outcomes. Long considered a cornerstone treatment to prevent sudden cardiac death, experts now speculate the overall survival benefit conveyed by the pricey technology may no longer be significant in patients with impaired heart function.

Findings from a new retrospective cohort study appear in Reviews in Cardiovascular Medicine.¹

This news comes amid a push within value-based care to ensure high-cost medical interventions deliver meaningful improvements in patient longevity and quality of life.

TTR-CA is a progressive disease of misfolded proteins produced by the liver that deposit in the heart, causing the muscle to become stiff, with symptoms like those of heart failure.^2,3 The condition can be fatal, and it often goes undiagnosed. Increasingly, patients are being identified as candidates for ICDs thanks to improved diagnostic techniques, with the authors highlighting technetium-99m pyrophosphate scintigraphy. Still, there is a significant gap in the literature regarding whether the device reduces mortality, and current clinical guidelines are not well established.

The researchers conducted a retrospective cohort study encompassing 463 patients diagnosed with TTR-CA between January 1, 2001, and December 31, 2024, across Mayo Clinic’s sites in Arizona, Florida, and Minnesota. The study compared survival outcomes of 206 patients who received an ICD against 257 who did not, with patients with nonischemic cardiomyopathy (NICM) who had ICDs serving as a control group to ensure a robust comparison. All-cause mortality was the primary outcome.

Patient Mortality Outcomes

There was a shorter median (IQR) follow-up among the patients who received ICDs vs those who did not receive ICDs: 6.8 years (4.5-9.0) vs 7.4 years (5.3-9.2). Primary prevention was the primary reason for most device implantations (76.2%). Overall, patients with TTR-CA had a median (IQR) age of 74.5 (68.0-80.0) years, and most were male patients (92.9%) and White (88.1%). ICD recipients were younger (71 vs 77 years; P = .001), and they had significantly higher rates of several damaging conditions:

• Hypertension: 62.6% vs 45.6% (P = .001)
• Chronic kidney disease (CKD): 62.6% vs. 44.4% (P = .001)
• Diabetes: 30.1% vs 21.8% (P = .043)

Also, their median left ventricular ejection fraction was lower (43% vs 54%; P = .007), and their N-terminal pro-B-type natriuretic peptide (NT-proBNP) level was higher (2259.0 pg/mL vs 1503.0 pg/mL; P = .007).

Of the 22 patients (10.6%) who were appropriately shocked by their ICD device, 18 patients were shocked because of ventricular tachycardia and 4 because of ventricular fibrillation. Six patients (3.0%) received inappropriate shocks, and 12 patients (5.8%) had device-related complications.

However, overall, the study findings present a striking paradox for payers and providers. Although the technology worked as intended, it did not translate into a survival advantage. Over 10 years of follow-up, the authors saw no significant difference in survival between patients with an ICD and those without an ICD (P = .74). In addition, comparing outcomes against the control cohort with NICM demonstrated the patients with TTR-CA had significantly worse survival outcomes (P = .034) over a median follow-up of 7.1 years (4.6-8.8), even when considering use of tafamadis—an oral medication approved to treat transthyretin amyloid cardiomyopathy⁴—or ICD indication (primary vs secondary prevention).

Using Cox regression analysis, the authors also found several mortality risk factors among the patients with TTR-CA:

• Older age: HR, 1.048 (P = .001)
• CKD: HR, 1.637 (P = .029)
• Troponin T above 50 ng/L: HR, 1.594 (P =.031)
• NT-proBNP above 3000 pg/mL: HR, 1.514 (P = .050)
• Ejection fraction below 40%: HR, 1.935 (P = .003)

Real-World Implications for Health Policy

The authors’ findings suggest several critical shifts in how to approach TTR-CA management. With the research indicating mortality may primarily be driven by pump failure brought on by disease progression vs sudden cardiac death, they suggest prioritizing funding and access to disease-modifying therapies to slow disease progression. For health policy to be effective, it must transition toward a model that favors biomarkers and functional status over routine device implantation for TTR-CA, the authors emphasize.

In addition, there needs to be greater consideration of the iatrogenic risks patients are exposed to, such as lead erosion and infections—reasons implicated for device-related complications in this analysis.

“Further prospective studies are needed to better understand the role of ICD in TTR cardiac amyloidosis patients and to improve treatment strategies for this patient population,” they conclude.

Potential limitations on these findings are its retrospective design; selection bias; the use of International Classification of Diseases, Tenth Revision codes for diagnosis; and temporal bias.

References

1. Raslan MA, Nabi HA, Odeh NB, et al. Prognostic factors and implantable cardioverter-defibrillator outcomes in transthyretin cardiac amyloidosis: a comprehensive retrospective study. Rev Cardiovasc Med. 2026;27(1):39760. doi:10.31083/RCM39760
2. Transthyretin amyloid cardiomyopathy (ATTR-CM). American Heart Association. Accessed February 17, 2026. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/transthyretin-amyloid-cardiomyopathy-attr-cm
3. Transthyretin amyloidosis (ATTR-CM). Cleveland Clinic. Reviewed May 1, 2022. Accessed February 17, 2026. https://my.clevelandclinic.org/health/diseases/17855-amyloidosis-attr
4. Tafamadis. Medline Plus. Updated April 15, 2022. Accessed February 17, 2026. https://medlineplus.gov/druginfo/meds/a622032.html