High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME)
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Alpha-Galactosidase A Activity Assay and Genetic Study of the GLA Gene
2.3. Demographic and Clinical Data Collection
2.4. Cardiac Evaluation
2.5. Statistical Analysis
3. Results
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Variables | Overall | FD | Non-FD | p |
---|---|---|---|---|
(n = 499) | (n = 8) | (n = 491) | ||
Demographic | ||||
Age, years | 66.4 ± 12.7 | 63.0 ± 7.0 | 66.5 ± 12.8 | 0.211 |
Men, n (%) | 336 (67.3) | 8 (100) | 328 (66.8) | 0.058 |
Ethnicity subgroup, n (%) | 0.0172 | |||
Canton | 284 (56.9) | 2 (25.0) | 282 (57.4) | |
Teochew | 85 (17.0) | 5 (62.5) | 80 (16.3) | |
Fujian | 11 (2.2) | 0 (0.0) | 11 (2.2) | |
Shanghai | 5 (1.0) | 0 (0.0) | 5 (1.0) | |
Others | 27 (5.4) | 1 (12.5) | 26 (5.3) | |
Unknown | 8 (17.4) | 0 (0.0) | 87 (17.7) | |
Diabetes, n (%) | 328 (65.7) | 1 (12.5) | 170 (34.6) | 0.274 |
Hypertension, n (%) | 376 (75.4) | 4 (50.0) | 372 (75.8) | 0.107 |
Aortic valve disease, n (%) | 48 (9.6) | 1 (12.5) | 47 (9.6) | 0.557 |
Mitral valve disease, n (%) | 64 (12.8) | 2 (25.0) | 62 (12.6) | 0.274 |
Heart failure,%) | 63 (12.6) | 4 (50.0) | 59 (12.0) | 0.011 |
Arial fibrillation, n (%) | 112 (22.4) | 4 (50.0) | 108 (22.0) | 0.080 |
Short PR interval (<120 ms), n (%) | 8 (1.6) | 0 (0.0) | 8 (1.6) | 1.000 |
IVST, mm | 15 ± 2 | 18 ± 6 | 15 ± 2 | 0.118 |
PWT, mm | 12 ± 3 | 13 ± 3 | 12 ± 3 | 0.255 |
LVEDD, mm | 43 ± 7 | 49 ± 10 | 43 ± 7 | 0.177 |
LVESD, mm | 30 ± 7 | 34 ± 9 | 29 ± 7 | 0.966 |
LVM, g | 222 ± 73 | 355 ± 202 | 220 ± 67 | 0.100 |
LVMI, g/m2 | 129 ± 38 | 181 ± 94 | 128 ± 36 | 0.159 |
LVEDV, mL | 93 ± 41 | 126 ± 34 | 92 ± 41 | 0.028 |
LVESV, mL | 42 ± 21 | 62 ± 30 | 41 ± 27 | 0.098 |
LVEF, % | 57 ± 10 | 53 ± 14 | 57 ± 10 | 0.371 |
LAV, ml | 66 ± 39 | 78 ± 32 | 66 ± 40 | 0.326 |
RWT | 0.57 ± 0.19 | 0.57 ± 0.19 | 0.57 ± 0.19 | 0.956 |
Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 |
---|---|---|---|---|---|---|---|---|
Age of diagnosis of FD, years | 74 | 59 | 53 | 69 | 59 | 69 | 59 | 63 |
Gender | Male | Male | Male | Male | Male | Male | Male | Male |
Ethnicity subgroup | Teochew | Canton | Wenzhou | Canton | Teochew | Teochew | Teochew | Teochew |
Initial presentation | Poorly controlled hypertension since age 65; incidental murmur with severe aortic regurgitation at age 71 | Exertional dyspnea and chest pain at age 49; hypertension; acute pulmonary edema with severe mitral regurgitation associated with chordal rupture at age 59, requiring mitral valve surgery | Dizziness with lacunar infarct/ischemic changes on MRI brain at age 46; diabetes; Exertional dyspnea at age 53 | Hypertension and diabetes at age 51; syncope with third degree AVB requiring pacemaker at age 57; onset of AF and heart failure at age 67; NSVT requiring upgrade of pacemaker to ICD at age 69; echo showed septal hypertrophy IVDT = 16mm with posterior wall akinesia | Chest pain, non-ST MINOCA at age 53; hypertension; obstructive sleep apnea; labelled HCM | Heart failure with reduced ejection fraction and AF at age 65; treated as dilated cardiomyopathy possibly caused by alcoholism | Ischemic heart disease requiring percutaneous coronary intervention at age 48; obstructive sleep apnea; AF onset at age 59 requiring catheter ablation | age 61; chest pain and exertional dyspnea at age 62; labelled HCM |
ECG findings | LVH with strain RBBB | LVH with strain | RBBB | AF, 3° AVB | LVH with strain | AF, LVH | AF, LVH | RBBB, LPFB, 2:1 AVB |
IVST, mm | 19 | 29 | 14 | 14 | 17 | 13 | 24 | 15 |
PWT, mm | 13 | 17 | 12 | 13 | 19 | 10 | 10 | 13 |
LVEDD, mm | 52 | 60 | 36 | 65 | 39 | 50 | 41 | 46 |
LVESD, mm | 33 | 43 | 23 | 50 | 29 | 38 | 26 | 32 |
LVM, g | 378 | 812 | 160 | 420 | 302 | 218 | 294 | 257 |
LVMI, g/m2 | 222 | 369 | 84 | 247 | 144 | 104 | 147 | 124 |
LVEF, % | 60 | 40 | 73 | 31 | 45 | 49 | 65 | 59 |
GLA activity, μmol/L wb/h | 0.55 | 0.43 | 0.09 | 0.54 | 0.76 | 0.64 | 0.52 | 1.04 |
IDUA/GLA ratio | 27 | 11 | 18 | 27 | 10 | 10 | 10 | 10 |
Creatinine, µmol/L | 204 | 116 | 89 | 118 | 87 | 74 | 98 | 83 |
eGFR, mL/min/1.73 m² | 26 | 58 | 84 | 53 | 83 | 88 | 72 | 86 |
Proteinuria | Urine TP/Cr: 6.62 mg/mg Cr | Urine TP/Cr: 0.05 mg/mg Cr | Urine TP/Cr: 0.04 mg/mg Cr | Spot urine albumin: <0.3 mg/L | Urine TP/Cr: 0.05 mg/mg Cr | 24 h urine protein: 0.13 g/24 h | Urine TP/Cr: 0.04 mg/mg Cr | 24 h urine protein: <0.04 g/24 h |
GLA gene mutation | IVS4 + 919G > A | IVS4 + 919G > A | IVS4 + 919G > A | IVS4 + 919G > A | IVS4 + 919G > A | IVS4 + 919G > A | IVS4 + 919G > A | IVS4 + 919G > A |
ERT | Decided not for ERT due to clinically advanced kidney disease; patient refused renal and endomyocardial biopsy | Started | Started | Decided not for ERT due to clinically advanced cardiac disease | Started | Started | Started | Planned to start |
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Fan, Y.; Chan, T.-N.; Chow, J.T.Y.; Kam, K.K.H.; Chi, W.-K.; Chan, J.Y.S.; Fung, E.; Tong, M.M.P.; Wong, J.K.T.; Choi, P.C.L.; et al. High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME). J. Clin. Med. 2021, 10, 2160. https://doi.org/10.3390/jcm10102160
Fan Y, Chan T-N, Chow JTY, Kam KKH, Chi W-K, Chan JYS, Fung E, Tong MMP, Wong JKT, Choi PCL, et al. High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME). Journal of Clinical Medicine. 2021; 10(10):2160. https://doi.org/10.3390/jcm10102160
Chicago/Turabian StyleFan, Yiting, Tsz-Ngai Chan, Josie T. Y. Chow, Kevin K. H. Kam, Wai-Kin Chi, Joseph Y. S. Chan, Erik Fung, Mabel M. P. Tong, Jeffery K. T. Wong, Paul C. L. Choi, and et al. 2021. "High Prevalence of Late-Onset Fabry Cardiomyopathy in a Cohort of 499 Non-Selective Patients with Left Ventricular Hypertrophy: The Asian Fabry Cardiomyopathy High-Risk Screening Study (ASIAN-FAME)" Journal of Clinical Medicine 10, no. 10: 2160. https://doi.org/10.3390/jcm10102160