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

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.

ECG Changes during Adult Life in Fabry Disease: Results from a Large Longitudinal Cohort Study

“…This effect of treatment (ERT) on the electrophysiological parameters cannot be studied given the small untreated patient sample, the treatment indication bias and the vast difference in age at which treatment was started between patients. Previous studies indicated that cardiac disease may progress despite ERT [19,42], and this is confirmed by the current study. The data from the current study, can, however, be used to analyze the effect of new FD therapies to see if they outperform current treatment in preventing the progression of cardiac disease.…”

“…Previous cross-sectional and longitudinal studies with a relatively small sample size show that early ECG abnormalities in FD patients include a short PR-interval and bradycardia [18,19]. A long P-wave duration, prolonged QRS-duration, QTc, high QRS-amplitude, Twave inversion and left frontal QRS-axis deviation may occur in later disease stages [19][20][21].…”

“…Previous cross-sectional and longitudinal studies with a relatively small sample size show that early ECG abnormalities in FD patients include a short PR-interval and bradycardia [18,19]. A long P-wave duration, prolonged QRS-duration, QTc, high QRS-amplitude, Twave inversion and left frontal QRS-axis deviation may occur in later disease stages [19][20][21]. There are no longitudinal studies to show electrophysiological development over time in different patient groups (e.g., men versus women with FD) and how this differs from age related changes in ECG parameters in healthy individuals.…”

A retrospective investigation to establish new screening approach for the detection of patients at high risk of Fabry disease in male left ventricular hypertrophy patients

“…Furthermore, from the results of our study, not the criterion used in LVH diagnosis of a Sokolow-Lyon index (SV1 + RV5) of ≥3.5 mV but the value of voltage (upper limit at 95% CI of 3.9 mV in non-FD patients) of ≥4.0 mV seemed to be better for raising the pretest probability for detection of FD. In Morimoto's study, their data showed that the majority of the male FD patients with LVH had SV1 + RV5 voltage of ≥4.0 mV [22]. When we focused on LVH patients with LVEF < 50% in our study cohort, there was only one patient with FD and that patient showed sinus rhythm and SV1 + RV5 > 4.0 mV with a strain pattern.…”

“…Namdar et al reported that Pend-Q interval < 40% was a highly sensitive and specific marker in the differentiation of FD among patients with LVH [13]. Furthermore, Morimoto et al recently reported the characteristics of an ECG in Japanese Fabry patients who were receiving long-term enzyme replacement therapy: shortening of the PQ interval and Pend-Q was seen in 7.5% and 47.5% of 40 FD patients, respectively [22]. These results suggest that shortening of Pend-Q seems to be a more important finding in FD patients.…”