Impact of Amyloidosis on Outcomes After TAVI

Cardiac amyloidosis (CA) is a systemic and progressive disease characterized by the accumulation of misfolded proteins in the myocardium, the conduction system, and valvular tissue. In patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI), concomitant CA is increasingly common, with an estimated prevalence between 8% and 16%. However, its impact on post-TAVI clinical outcomes remains uncertain.

This observational, retrospective, multicenter study used the global TriNetX network (which includes over 180 million health records) to analyze the incidence of adverse events at one year in patients, with or without a diagnosis of amyloidosis, who underwent TAVI between January 2005 and December 2023.

The primary endpoint was a composite of heart failure (HF), ischemic stroke, permanent pacemaker (PPM) implantation, acute kidney injury (AKI), and all-cause mortality at one year. Secondary endpoints were the individual components.

The total population included 52,885 patients, of whom 589 had amyloidosis and 52,296 did not. The mean age was 78±8 years, and approximately 40% of subjects were women. Self-expanding valves (CoreValve, Evolut R, and Evolut PRO) were the most common type. The transthyretin (ATTR) form was the most prevalent.

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Patients with amyloidosis presented a higher burden of comorbidities: hypertension (91.3% vs. 82.5%), prior heart failure (74% vs. 59.2%), atrial fibrillation (53.8% vs. 36.5%), chronic kidney disease (47.4% vs. 31.5%), ischemic heart disease (86.8% vs. 77.2%), and diabetes mellitus (41.9% vs. 36.9%). Associated valvular diseases were also more frequent, both mitral (42.1% vs. 30.2%) and tricuspid (21.7% vs. 14.6%).

In terms of outcomes, a Cox analysis demonstrated a significantly higher risk of combined events for the amyloidosis group (hazard ratio [HR] 1.27; 95% confidence interval [CI]: 1.08–1.49). Heart failure was the most frequent cause (HR 1.37; 95% CI: 1.10–1.70), followed by stroke (HR 1.67; 95% CI: 1.16–2.40) and the need for PPM implantation (HR 2.25; 95% CI: 1.15–4.41). There were no significant differences in the incidence of AKI (HR 1.07; 95% CI: 0.83–1.38) or mortality (HR 0.77; 95% CI: 0.54–1.10).

Notably, patients with amyloidosis presented a higher prevalence of baseline conduction disorders: atrioventricular or bundle branch block in 38.4% vs. 24.1% (standardized mean difference 0.31), and other conduction abnormalities (such as hemiblock or nonspecific alterations) in 29.9% vs. 15.6%. This finding correlated with the higher risk of requiring a PPM during follow-up (HR 2.25; 95% CI: 1.15–4.41).

Conclusion 

The presence of cardiac amyloidosis in patients undergoing TAVI—although underdiagnosed (<1% in this cohort)—is associated with a higher risk of heart failure, stroke, and pacemaker implantation at one year, without a significant increase in mortality or incidence of acute kidney injury.

Early detection of this condition could influence key therapeutic decisions, such as the choice of prosthesis type (potentially favoring balloon-expandable valves) and antithrombotic strategy, considering that the combination of restrictive cardiomyopathy and atrial stasis characteristic of amyloidosis increases susceptibility to thromboembolic events.

Original Title: Impact of amyloidosis on outcomes after transcatheter aortic valve implantation.

Reference: Luigi Gerra et al. Rev Esp Cardiol. 2025;78(10):886–895.