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

Alberto Cipriani; Laura De Michieli; Aldostefano Porcari; Luca Licchelli; Giulio Sinigiani; Giacomo Tini; Mattia Zampieri; Eugenio Sessarego; Alessia Argirò; Carlo Fumagalli; Monica De Gaspari; Roberto Licordari; Domitilla Russo; Gianluca Di Bella; Federico Perfetto; Camillo Autore; Beatrice Musumeci; Marco Canepa; Marco Merlo; Gianfranco Sinagra; Dario Gregori; Sabino Iliceto; Martina Perazzolo Marra; Francesco Cappelli; Claudio Rapezzi

doi:10.1016/j.jaccao.2022.08.007

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

JACC CardioOncol. 2022 Sep 7;4(4):458-470. doi: 10.1016/j.jaccao.2022.08.007. eCollection 2022 Nov.

Authors

Alberto Cipriani¹, Laura De Michieli¹, Aldostefano Porcari², Luca Licchelli¹, Giulio Sinigiani¹, Giacomo Tini³, Mattia Zampieri⁴, Eugenio Sessarego⁵, Alessia Argirò⁴, Carlo Fumagalli⁴, Monica De Gaspari¹, Roberto Licordari⁶, Domitilla Russo³, Gianluca Di Bella⁶, Federico Perfetto^{4

7}, Camillo Autore³, Beatrice Musumeci³, Marco Canepa^{5

8}, Marco Merlo², Gianfranco Sinagra², Dario Gregori¹, Sabino Iliceto¹, Martina Perazzolo Marra¹, Francesco Cappelli^{4

7}, Claudio Rapezzi^{9

10}

Affiliations

¹ Department of Cardiac, Thoracic and Vascular Sciences and Public Health, University of Padua, Padua, Italy.
² Center for Diagnosis and Treatment of Cardiomyopathies, Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano-Isontina, University of Trieste, Trieste, Italy.
³ Department of Clinical and Molecular Medicine, Sapienza University, Rome, Italy.
⁴ Tuscan Regional Amyloidosis Centre, Careggi University Hospital, Florence, Italy.
⁵ Department of Internal Medicine, University of Genova, Genova, Italy.
⁶ Department of Cardiology, University of Messina, Messina, Italy.
⁷ Cardiomyopathy Unit, Careggi University Hospital, University of Florence, Florence, Italy.
⁸ Cardiovascular Unit, Department of Internal Medicine, University of Genova, Ospedale Policlinico San Martino Istituto Ricovero e Cura a Carattere Scientifico, Genova, Italy.
⁹ Cardiothoracic Department, University of Ferrara, Ferrara, Italy.
¹⁰ Maria Cecilia Hospital, Gruppo Villa Maria Care and Research, Cotignola, Ravenna, Italy.

Abstract

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 = 120, ATTR CA: n = 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 = 0.015), higher New York Heart Association functional class (P = 0.016), and natriuretic peptides (P = 0.041); in ATTR CA, LQRSVs were independently associated with pericardial effusion (P = 0.008) and lower tricuspid annulus peak systolic excursion (P = 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 = 0.031) and ATTR CA (HR: 2.64; 95% CI: 1.82-20.17; P = 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 + LQRSV model: 0.87 [95% CI: 0.81-0.93]; P = 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.

Keywords: AL, light chain amyloidosis; ATTR, transthyretin amyloidosis; ATTR-v, variant transthyretin; ATTR-wt, wild-type transthyretin; AUC, area under the curve; BNP, B-type natriuretic peptide; CA, cardiac amyloidosis; CMR, cardiac magnetic resonance; CV, cardiovascular; ECG, electrocardiogram; LQRSV, low QRS voltages; LV, left ventricle; LVEDD, left ventricular end-diastolic diameter; NAC, National Amyloidosis Centre; NT-proBNP, N-terminal pro–B-type natriuretic peptide; NYHA, New York Heart Association; ROC, receiver-operating characteristic; RV, right ventricular; TAPSE, tricuspid annulus peak systolic excursion; cardiac amyloidosis; echocardiography; electrocardiography; low QRS voltages; prognostic significance; risk stratification.