Mechanisms of heart failure in transthyretin vs. light chain amyloidosis

Cardiac amyloidosis (CA) leads to signs and symptoms of heart failure (HF). The mechanisms of biventricular dysfunction and their impact on outcome in subtypes of CA are poorly understood. Our aim was to compare right ventricular (RV) and left ventricular (LV) parameters in patients with light chain (AL) and wild-type transthyretin amyloidosis (ATTRw) and evaluate their ability to predict cardiac outcome.

We included patients with CA into a prospective registry. Baseline assessment included biventricular 2D speckle tracking imaging parameters. Patients were followed-up in regular intervals. The composite endpoint was defined as cardiovascular death, heart transplantation or ventricular assist device implantation, and HF hospitalization. We included 122 patients with CA. Sixty-two of these patients (50.8%) were diagnosed with ATTRw and 60 (49.2%) with AL. In ATTRw, parameters of RV size and function correlated well with symptom severity and only morphological and functional parameters of the RV predicted outcome. RV free wall strain was the only independent predictor of outcome with a hazard ratio (HR) of 1.185 [95% confidence interval (CI) 1.047-1.342, P = 0.007]. In AL on the other hand, RV function correlated well with symptoms but was not associated with outcome. In contrast, global longitudinal strain of the LV (LV-GLS) was predictive for outcome. After adjusting in a multivariable model, LV-GLS remained predictive with a HR of 1.180 (95% CI 1.032-1.348, P = 0.015).

Our data suggest that mechanisms underlying HF differ between ATTRw and AL. This may have substantial implications in particular in light of emerging therapies for both subtypes of CA.