Electrocardiographic Characteristics and Their Correlation with Echocardiographic Alterations in Fabry Disease.

Matthew Zada,Anita C Boyd,Michel C Tchan,Norman Sadick,Siddharth J Trivedi,Liza Thomas,Queenie Lo,Mehmet Harapoz,Kerry Devine

doi:10.3390/jcdd9010011

Abstract

Fabry disease (FD) is an X-linked disorder with α-galactosidase A deficiency. Males (>30 years) and females (>40 years) often present with cardiac manifestations, predominantly left ventricular hypertrophy (LVH). The aim of this study was to evaluate electrocardiographic (ECG) characteristics within FD patients to identify gender related differences, and to additionally explore the association of ECG parameters with structural and functional alterations on transthoracic echocardiography (TTE). Retrospective cross-sectional analysis of 45 FD patients with contemporaneous ECG and TTE was performed and compared to age and gender matched healthy controls. FD patients demonstrated alterations in several ECG parameters particularly in males, including prolonged P-wave duration (91 vs. 81 ms, p = 0.022), prolonged QRS duration (96 vs. 84 ms, p < 0.001), increased R-wave amplitude in lead I (8.1 vs. 5.7 mV, p = 0.047), increased Sokolow–Lyon index (25 vs. 19 mV, p = 0.002) and were more likely to meet LVH criteria (31% vs. 7%, p = 0.006). FD patients with impaired basal longitudinal strain (LS) on TTE were more likely to meet LVH criteria (41% vs. 0%, p = 0.018). Those with more advanced FD (increased LV wall thickness on TTE) were more likely to meet LVH criteria but additionally demonstrated prolonged ventricular depolarization (QRS duration 101 vs. 88 ms, p = 0.044). Therefore, alterations on ECG demonstrating delayed atrial activation, delayed ventricular depolarization and evidence of LVH were more often seen in male FD patients. Impaired basal LS, a TTE marker of early cardiac involvement, correlated with ECG abnormalities. Increased LV wall thickness on TTE, a marker of more advanced FD, was associated with more severe ECG abnormalities.

Highlights

We examined ECG findings in subgroups of Fabry disease (FD) patients based on transthoracic echocardiography (TTE) criteria: increased left ventricular (LV) wall thickness vs. normal LV wall thickness, impaired global longitudinal strain (GLS) vs. normal GLS
The QRS duration was significantly longer in FD patients compared to controls (96 vs. ms, p < 0.001) and again, QRS duration was significantly longer in male FD patients (103 vs. ms, p < 0.001), but not so in female FD patients (87 vs. 82 ms, p = 0.271)
We have proposed a model which highlights these findings and demonstrates corresponding ECG and TTE findings that could be expected with disease progression in FD (Figure 3): In early-stage FD, LV wall thickness, GLS and basal longitudinal strain (LS) are normal—ECG characteristics may include shortened PQ interval and QRS duration due to enhanced conduction; In intermediate stage FD, LV

Summary

Introduction

There are a variety of clinical manifestations including neurological, gastrointestinal, renal and cardiac in affected individuals [2]. FD patients with cardiac involvement develop several manifestations, typically with progressive increase in left ventricular (LV) wall thickness (on transthoracic echocardiography (TTE) or on cardiac magnetic resonance imaging (CMR)), significant life-threatening arrythmias or conduction defects, interstitial remodeling and myocardial fibrosis (as demonstrated on myocardial biopsy) [4]. Electrocardiographic (ECG) alterations have been reported including altered conduction, demonstrated by a prolonged PQ interval and QRS duration, as well as ECG features of LVH [5,6,7]. Prior studies of FD patients have shown a correlation between prolonged QRS duration on ECG and LV mass on TTE [8] and CMR [9]

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