Are classic predictors of voltage valid in cardiac amyloidosis? A contemporary analysis of electrocardiographic findings Brett W. Sperry a, ⁎, Michael N. Vranian a , Rory Hachamovitch a , Hariom Joshi b , Meghann McCarthy b , Asad Ikram a , Mazen Hanna a a Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA b Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, USA abstract article info Article history: Received 29 February 2016 Received in revised form 29 March 2016 Accepted 3 April 2016 Available online 8 April 2016 Background: Low voltage electrocardiography (ECG) coupled with increased ventricular wall thickness is the hall- mark of cardiac amyloidosis. However, patient characteristics influencing voltage in the general population, in- cluding bundle branch block, have not been evaluated in amyloid heart disease. Methods: A retrospective analysis was performed of patients with newly diagnosed cardiac amyloidosis from 2002 to 2014. ECG voltage was calculated using limb (sum of QRS complex in leads I, II and III) and precordial (Sokolow: S in V1 plus R in V5–V6) criteria. The associations between voltage and clinical variables were tested using multivariable linear regression. A Cox model assessed the association of voltage with mortality. Results: In 389 subjects (transthyretin ATTR 186, light chain AL 203), 30% had conduction delay (QRS N 120 ms). In those with narrow QRS, 68% met low limb, 72% low Sokolow and 57% both criteria, with lower voltages found in AL vs ATTR. LV mass index as well as other typical factors that impact voltage (age, sex, race, hypertension, BSA, and smoking) in the general population were not associated with voltage in this cardiac amyloidosis cohort. Pa- tients with LBBB and IVCD had similar voltages when compared to those with narrow QRS. Voltage was signifi- cantly associated with mortality (p b 0.001 for both criteria) after multivariable adjustment. Conclusion: Classic predictors of ECG voltage in the general population are not valid in cardiac amyloidosis. In this cohort, the prevalence estimates of ventricular conduction delay and low voltage are higher than previously re- ported. Voltage predicts mortality after multivariable adjustment. © 2016 Elsevier Ireland Ltd. All rights reserved. Keywords: Infiltrative cardiomyopathy Cardiac amyloidosis Electrocardiography Voltage Bundle branch block 1. Introduction Amyloidosis is a protein misfolding disorder characterized by fibril- lary protein deposition into tissue. Cardiac amyloidosis (CA) almost ex- clusively results from pathologic deposition of immunoglobulin light chains (AL) or the transthyretin protein (ATTR). This leads to fibrosis, myocardial dysfunction and conduction disease. Low voltage electrocardiography (ECG) coupled with increased ventricular wall thickness on echocardiography is the classic hall- mark of amyloid cardiomyopathy. This phenomenon was first de- scribed by Carroll utilizing limb and precordial (Sokolow) voltage indices [1]. Nevertheless, low voltage is not ubiquitous in amyloid heart disease. Previous reports suggest that only about 60% of pa- tients with AL and 25–40% with ATTR meet low voltage criteria [2]. In another analysis, low limb voltage was found in approximately 35% of patients, while 60% had low Sokolow voltage ≤ 15 mm [3]. There are many factors impacting ECG voltage in the general popu- lation; body mass index [4–7] and smoking [7] have been associated with a lower ECG voltage while blood pressure [4,5], African American race [5,8] and male gender [5,7] yield higher voltage measurements. Similarly, bundle branch block and pacing have been shown to alter measured ECG voltage compared to normal conduction [9–11]. Studies of amyloidosis have commonly excluded patients with bundle branch block and paced rhythms as a result. Anecdotally, conduction delay is quite common in cardiac amyloidosis, yet the precise frequency of these ventricular conduction abnormalities is unknown. We sought to assess whether the classic factors that impact voltage in the general population are valid in amyloid heart disease. Similarly, because voltage predicts cardiovascular outcomes in the general popu- lation [12], we set to investigate whether this held true in cardiac amyloidosis. 2. Methods 2.1. Patient population A retrospective cohort study was performed in patients with cardiac amyloidosis at our institution diagnosed between 2002 and 2014. Pa- tients were considered to have cardiac amyloidosis and included in International Journal of Cardiology 214 (2016) 477–481 ⁎ Corresponding author at: Cleveland Clinic Foundation, Department of Cardiovascular Medicine, 9500 Euclid Avenue, Desk J3-5, Cleveland, OH 44195, USA. E-mail address: sperryb@ccf.org (B.W. Sperry). http://dx.doi.org/10.1016/j.ijcard.2016.04.030 0167-5273/© 2016 Elsevier Ireland Ltd. All rights reserved. Contents lists available at ScienceDirect International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard