Fabry disease (FD) is an X-chromosomal inherited lysosomal storage disease resulting in intracellular storage of globotriaosylceramide. Cardiac involvement is most frequently manifested as left ventricular hypertrophy. However, patients with FD may also have from various conduction abnormalities particularly affecting atrioventricular (AV) conduction. The present study was designed to analyze primarily AV conduction abnormalities on baseline electrocardiograms of patients with FD and to investigate the correlation with echocardiographic findings. Electrocardiograms at rest of 207 patients with FD were compared to echocardiograms. PQ-interval shortening and first-degree AV block could be found in only 29 cases (14%) and 3 cases (1.4%), respectively. No echocardiographic differences could be found in patients with and without PQ-interval shortening, including left ventricular hypertrophy, atrial size, and diastolic parameters. Furthermore, no correlation of the PQ interval with any echocardiographic parameters was detected. There was no difference between men and women in baseline clinical and electrocardiographic parameters. In conclusion, shortening of the PQ interval was not a common electrocardiographic finding in patients newly diagnosed with FD. Furthermore, no correlation with typical echocardiographic findings or disease stage in FD at baseline could be found.
Fabry disease (FD), also known as Morbus Anderson-Fabry, angiokeratoma corporis diffusum, or ceramide trihexosidase, is an X-chromosomal inherited lysosomal storage disease associated with a deficient activity of the lysosomal enzyme α-galactosidase A. The resulting intracellular storage of globotriaosylceramide (Gb3) is characteristic of the disease. This accumulation can be detected in the vascular endothelium and in many organs including the heart, kidneys, and skin. Cardiac involvement occurs in up to 78% of these patients and is manifested as left ventricular (LV) hypertrophy, arrhythmias, or coronary heart disease. Several electrocardiographic characteristics have been described in patients with FD, including short or prolonged PQ interval. Whether abnormalities in the PQ duration, however, are of diagnostic value in patients with FD and if they correlate with specific clinical or echocardiographic findings remain elusive. The aim of this study was to analyze atrioventricular (AV) conduction abnormalities on surface electrocardiograms of patients with newly diagnosed FD and to investigate their correlation with echocardiographic findings.
Methods
Electrocardiographic and echocardiographic findings of 207 patients ≥18 years of age with newly diagnosed FD from 2 university clinics (Zurich, Switzerland, and Mainz, Germany) were studied. Diagnosis of patients was based on measurement of enzyme activity in leukocytes and confirmed by genetic analysis. Twelve-lead surface electrocardiograms at initial diagnosis were independently analyzed by 2 experienced readers (MN and FD) blinded for the stage of the disease. Standard criteria for electrocardiographic findings were applied, including PQ interval (typical 120 to 200 ms) and QRS duration (typical <120 ms). None of the patients included in the analysis were on enzyme replacement therapy at the time of electrocardiography.
All echocardiographic examinations were performed by experienced operators (RJ, CK, and MN). Standard 2-dimensional M-mode echocardiogram from the parasternal long-axis view was used for measurement of LV chamber dimensions including ventricular septal and posterior wall thickness and the diameter of the left atrium and the sinus of Valsalva. LV mass was calculated with the formula of Devereux et al. LV hypertrophy was defined as an LV mean mass index >134 g/m 2 in men and >110 g/m 2 in women. LV volumes were calculated using the area–length method. Longitudinal LV systolic function was measured with myocardial Doppler imaging (systolic velocities of the mitral medial and lateral annulus) in the standard apical 4-chamber view. Diastolic function was analyzed as previously published. The study was approved by the local ethics committees of the 2 institutions. Continuous variables are presented as mean ± SD and compared using Mann-Whitney U test. Categorical variables were compared using Fisher’s exact test. Bivariate correlation analysis was performed using Pearson correlation coefficient. Analyzes were performed using SPSS 17.0 (SPSS, Inc., Chicago, Illinois). A p value <0.05 was considered statistically significant.
Results
Baseline characteristics are shown in Table 1 . There were 85 men and 122 women with FD. Short PQ intervals were observed in 29 patients (14%). Prolonged PQ intervals and ventricular bundle branch blocks with a QRS duration >120 ms were seen in only 3 patients (1.4%) and 7 patients (3.4%), respectively. No gender-specific differences were observed in clinical or electrocardiographic parameters. None of the patients had myocardial fibrosis at baseline. No significant differences in clinical or echocardiographic parameters were observed when patients with PQ-interval shortening were compared to those with a normal PQ interval ( Table 2 ). Similarly, no significant correlation of the PQ interval with echocardiographic parameters was detected ( Table 3 ). In particular, no differences or significance in LV mean mass index, left atrial diameter, and diastolic indexes were found. Furthermore, there was no difference in PQ interval between patients with and without LV hypertrophy ( Figure 1 ).
| Variable | All | Men | Women | p Value ⁎ |
|---|---|---|---|---|
| (n = 207) | (n = 85) | (n = 122) | ||
| Clinical characteristics | ||||
| Age (years) | 40 ± 14 | 39 ± 12 | 42 ± 14 | 0.13 |
| Systolic blood pressure (mm Hg) | 118 ± 36 | 117 ± 43 | 119 ± 32 | 0.79 |
| Diastolic blood pressure (mm Hg) | 68 ± 21 | 66 ± 24 | 69 ± 18 | 0.54 |
| Mean blood pressure (mm Hg) | 86 ± 26 | 85 ± 31 | 87 ± 23 | 0.62 |
| Heart rate (beats/min) | 62 ± 10 | 59 ± 9 | 65 ± 11 | 0.08 |
| Pacemaker | 2 (1%) | 1 (1%) | 1 (1%) | — |
| Electrocardiographic characteristics | ||||
| PQ interval (ms) | 139 ± 29 | 142 ± 29 | 136 ± 28 | 0.17 |
| PQ interval <120 ms † | 29 (14%) | 10 (5%) | 19 (9%) | 0.43 |
| PQ interval >200 ms | 3 (1.4%) | 1 (0.4%) | 2 (1%) | 0.78 |
| Delta wave | 0 | 0 | 0 | — |
| QRS duration >120 ms | 7 (3.4%) | 4 (1.9%) | 3 (1.5%) | 0.38 |
| Atrial fibrillation | 2 (1%) | 1 (1%) | 1 (1%) | — |
| Echocardiographic characteristics | ||||
| Sinus of Valsalva (mm) | 26 ± 8 | 29 ± 10 | 25 ± 6 | <0.005 |
| Ventricular septal thickness (mm) | 12 ± 5 | 12 ± 5 | 11 ± 5 | 0.21 |
| Posterior wall thickness (mm) | 11 ± 4 | 12 ± 4 | 11 ± 3 | <0.05 |
| Left ventricular mass (g/m 2 ) | 145 ± 73 | 174 ± 72 | 126 ± 68 | <0.001 |
| Left ventricular hypertrophy | 96 (46%) | 47 (23%) | 49 (23%) | 0.76 |
| Left atrial size (mm) | 32 ± 10 | 33 ± 13 | 32 ± 9 | 0.96 |
| Early diastolic peak velocity (cm/s) | 80 ± 26 | 78 ± 29 | 81 ± 24 | 0.44 |
| Last diastolic peak velocity (cm/s) | 56 ± 20 | 57 ± 22 | 56 ± 20 | 0.71 |
| Early/late diastolic peak ratio | 1.5 ± 0.51 | 1.47 ± 0.55 | 1.52 ± 0.51 | 0.65 |
| Isovolumetric relaxation time (ms) | 92 ± 24 | 95 ± 27 | 90 ± 23 | 0.28 |
† Percentages are calculated as a part of the entire cohort.
| Variable | PQ Shortening | p Value ⁎ | |
|---|---|---|---|
| Yes | No | ||
| (n = 29) | (n = 102) | ||
| Age (years) | 38 ± 14 | 41 ± 13 | 0.48 |
| Heart rate (beats/min) | 64 ± 11 | 62 ± 10 | 0.56 |
| Sinus of Valsalva (mm) | 26 ± 8 | 27 ± 7 | 0.56 |
| Ventricular septal thickness (mm) | 13 ± 5 | 12 ± 4 | 0.78 |
| Posterior wall thickness (mm) | 13 ± 3 | 13 ± 3 | 0.77 |
| Left ventricular mass (g/m 2 ) | 140 ± 87 | 148 ± 63 | 0.65 |
| Left atrial size (mm) | 33 ± 10 | 33 ± 8 | 0.82 |
| Early diastolic peak velocity (cm/s) | 90 ± 22 | 85 ± 18 | 0.39 |
| Late diastolic peak velocity (cm/s) | 63 ± 20 | 59 ± 15 | 0.37 |
| Early/late diastolic peak ratio | 1.5 ± 0.5 | 1.6 ± 0.5 | 0.6 |
| Isovolumetric relaxation time (ms) | 95 ± 26 | 96 ± 18 | 0.87 † |
⁎ Comparison of presence to absence of PQ shortening.
† Percentages are calculated as a part of all cases with PQ shortening.
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