Transthyretin Cardiac Amyloidosis and Aortic Stenosis: What is the Connection and Therapeutic Implications? A Systematic Review and Metanalysis

Background:
There is growing interest in the observed incidence of transthyretin cardiac amyloidosis (TTR-CA) in elderly patients with aortic stenosis (AS). Approximately 16% of patients with severe AS undergoing aortic valve replacement (AVR) have TTR-CA. Outcomes after aortic valve replacement appear worse in patients with concomitant TTR-CA.

Methods:
Publications in PubMed, Cochrane Library, and Embase databases were systematically searched from January 2010 to September 2018 using the keywords transthyretin, amyloidosis, and aortic stenosis. All studies published in English that reported the prevalence, association and outcomes of TTR-CA in patients with AS were included in the metanalysis.

Results:
A total of 7 retrospective and prospective studies (n= 765) met inclusion criteria. A total of 103 patients had concomitant AS and TTR-CA. Five studies included 578 patients (mean age 79.7 years) with AS of which 60 patients had TTR-CA. The prevalence of TTR-CA was 10% (95% CI 0.05-0.15) Iˆ2= 74.6%. Four studies addressed clinical outcomes after AVR in patients with TTR-CA. The mean follow-up was 21 months, the mean age was 76 years, and the pooled mortality was 37% (95% CI 0.25- 0.49), Iˆ2=0%.

Conclusions:
The relationship between AS and TTR-CA is not well understood. This systematic review and metanalysis suggests that TTR-CA is common in elderly patients with AS and these patients tend to have high mortality rates after AVR. The significant incidence of the two diseases occurring simultaneously warrants further investigation to improve management strategies in the future.