Cardiac Amyloidosis in Aortic Stenosis: From Suspicion to Treatment. A Comprehensive Literature Review

Abstract

Background: Cardiac amyloidosis (CA) and degenerative aortic stenosis (AS) are both age-related cardiovascular conditions whose coexistence has been increasingly recognized over the past decade. Transthyretin cardiac amyloidosis (ATTR-CA) affects an estimated 4% to 16% of patients with severe AS referred for aortic valve replacement, and this dual pathology confers a substantially worse prognosis than either condition alone. Despite growing awareness, CA remains underdiagnosed in AS populations, and optimal screening, diagnostic, and therapeutic strategies for patients with concomitant AS and CA are still evolving. Objective: To synthesize the current evidence on the epidemiological overlap, shared pathophysiological mechanisms, diagnostic approaches, prognostic implications, and therapeutic strategies for patients with concomitant cardiac amyloidosis and aortic stenosis, and to translate that evidence into a stepwise screening algorithm for clinical practice. Methods: A comprehensive literature search was conducted across PubMed/MEDLINE, Scopus, Cochrane Library, and ClinicalTrials.gov from January 2017 through February 2026. Priority was given to randomized controlled trials, meta-analyses, prospective cohort studies, and clinical practice guidelines from major cardiovascular societies. The GRADE framework was applied to assess the quality of evidence. Results: The pooled prevalence of ATTR-CA among patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) is approximately 13%. Patients with dual pathology (AS-CA) have significantly higher all-cause mortality than those with AS alone (RR = 2.60; 95% CI: 1.48-4.57). A multiparametric diagnostic approach integrating clinical red flags, electrocardiographic voltage-mass discordance, advanced echocardiography with strain imaging, bone scintigraphy (99mTc-PYP/DPD/HMDP), and cardiac magnetic resonance imaging is essential for accurate identification. TAVR appears safe and is associated with improved survival compared with medical therapy or surgical aortic valve replacement in AS-CA patients. Disease-modifying therapies including TTR stabilizers (tafamidis, acoramidis) and gene-silencing agents (patisiran, vutrisiran) have demonstrated efficacy in ATTR-CA and represent promising adjunctive treatments. Conclusions: The recognition of concomitant CA in AS patients is crucial for optimal risk stratification and therapeutic decision-making. Systematic screening protocols integrating multimodality imaging should be implemented in elderly patients with AS. TAVR combined with disease-specific ATTR-CA therapy represents the most evidence-supported approach for this patient population. Future prospective trials are needed to refine screening algorithms and to evaluate the synergistic benefit of combined valve intervention and amyloidosis-directed therapy.