Low QRS Voltages in Cardiac Amyloidosis: Clinical Correlates and Prognostic Value

BACKGROUND Low QRS voltages (LQRSVs) are a common electrocardiographic feature in patients with light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR) cardiac amyloidosis (CA). OBJECTIVES The aim of this study was to identify clinical and echocardiographic correlates of LQRSV and to investigate their prognostic significance in patients with CA. METHODS This was a multicenter, retrospective study performed in 6 CA referral centers including consecutive patients with AL- and ATTR-CA. LQRSVs were defined as a QRS amplitude #5 mm (0.5 mV) in all peripheral leads. The study outcome was cardiovascular (CV) mortality. RESULTS Overall, 411 (AL-CA: n ¼ 120, ATTR-CA: n ¼ 291) patients were included. LQRSVs were present in 66 (55%) patients with AL-CA and 103 (35%) with ATTR-CA (P < 0.001). In AL-CA, LQRSVs were independently associated with younger age (P ¼ 0.015), higher New York Heart Association functional class (P ¼ 0.016), and natriuretic peptides (P ¼ 0.041); in ATTR-CA, LQRSVs were independently associated with pericardial effusion (P ¼ 0.008) and lower tricuspid annulus peak systolic excursion (P ¼ 0.038). During a median follow-up of 33 months (Q1-Q3: 21-46), LQRSVs independently predicted CV death in both AL-CA (HR: 1.76; 95% CI: 2.41-10.18; P ¼ 0.031) and ATTR-CA (HR: 2.64; 95% CI: 1.82-20.17; P ¼ 0.005). Together with the National Amyloidosis Centre (NAC) staging, LQRSVs provided incremental prognostic value in ATTR-CA (AUC for NAC model: 0.83 [95% CI: 0.77-0.89]; AUC for NAC þ LQRSV model: 0.87 [95% CI: 0.81-0.93]; P ¼ 0.040). CONCLUSIONS LQRSVs are common but not ubiquitous in CA; they are more frequent in AL-CA than in ATTR-CA. LQRSVs reflect an advanced disease stage and independently predict CV death. In ATTR-CA, LQRSVs can provide incremental prognostic accuracy over the NAC staging system in patients with intermediate risk.