Characteristics of the Electrocardiogram in Japanese Fabry Patients Under Long-Term Enzyme Replacement Therapy.

Satoshi Morimoto,Michihiro Yoshimura,Makoto Kawai,Ayumi Nojiri,Ikuko Anan,Toya Ohashi,Takahiro Shibata,Eiko Fukuro,Hiroyuki Ida,Yoshikatsu Eto,Ken Sakurai,Kenichi Hongo,Masahisa Kobayashi,Hiroshi Kobayashi

doi:10.3389/fcvm.2020.614129

Satoshi Morimoto, Michihiro Yoshimura + Show 12 more

Open Access

https://doi.org/10.3389/fcvm.2020.614129

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Abstract

Objective: An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT).Methods: We analyzed the ECGs of 40 Fabry patients (male, n = 17; female, n = 23) before and after treatment with ERT. To evaluate the atrio-ventricular conduction, the PQ interval, corrected PQ and PQ minus P-wave in lead II (Pend-Q) were calculated. The QRS duration, QTc, Sokolow-Lyon index, and strain pattern were also examined.Results: At the baseline, the shortening of the PQ interval, corrected PQ and Pend-Q was identified in 7.5, 25.0, and 47.5% of cases, respectively. The prolongation of QRS duration and QTc was found in 7.5 and 40.0% of cases, respectively. The strain pattern was mainly identified in female patients, irrespective of left ventricular hypertrophy (LVH). During long-term ERT, the PQ interval, corrected PQ and Pend-Q did not change significantly. The QRS duration was significantly prolonged in both genders, whereas the QTc was significantly prolonged only in male patients. A subgroup analysis revealed that the prolongation of the QRS duration and QTc only occurred in male patients with LVH and only occurred in female patients with the classical type mutation. The prevalence of the strain was significantly increased only in male patients with LVH.Conclusions: These results suggest that the shortening of the Pend-Q is a specific finding in Japanese Fabry patients, and the strain pattern without LVH in female patients can be considered Fabry disease. During long-term ERT, prolongation of the QRS duration and QTc can indicate the progression of myocardial damage in male patients with LVH and in female patients with the classical type mutation.

Highlights

Fabry disease is an inherited metabolic disorder due to a mutation in the gene that encodes lysosomal enzyme alphagalactosidase A (GLA)
Significant gender differences were observed in the age, enzyme replacement therapy (ERT) duration and LVMI, with a younger age, longer duration of ERT, and larger LVMI being noted in male patients than in female patients
Fewer than half of the patients were treated with either agalsidase alpha or agalsidase beta; the majority of the patients were instead treated with both types of ERT during long-term follow up, partially due to the global shortage of PQ interval Corrected PQ Pend-Q QRS duration QTc Sokolow-Lyon Prevalence of left ventricular hypertrophy (LVH) Prevalence of strain

Summary

Introduction

Fabry disease is an inherited metabolic disorder due to a mutation in the gene that encodes lysosomal enzyme alphagalactosidase A (GLA). Major affected organs related to the prognosis of Fabry disease are the heart, kidney and central nervous system [3,4,5]. Cardiac involvement is important because more than half of deaths in Fabry disease patients are due to cardiovascular events [3, 6]. We previously reported the beneficial effect of enzyme replacement therapy (ERT) on echocardiographic findings [7] and the characteristics of late-gadolinium enhancement in our cohort of Fabry disease patients [8]. An electrocardiogram (ECG) is a very important tool for depicting the cardiac manifestations of various heart diseases

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