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).

Left ventricular hypertrophy (LVH) caused by cardiac variant Fabry disease (FD) is typically late-onset and may mimic LVH caused by abnormal loading conditions. We aimed to determine the prevalence of FD in a non-selective patient population of everyday practice presenting with LVH, including those with hypertension and valve disease. We measured plasma alpha-galactosidase A activity using dried blood spot tests in 499 (age = 66 ± 13 years; 336 men) Hong Kong Chinese patients with LVH defined as maximal LV septal/posterior wall thickness ≥13 mm on echocardiography. Patients with low enzyme activity underwent mutation analysis of the GLA gene. Eight (age = 53-74 years; all men) unrelated patients (1.6%) had low plasma alpha-galactosidase A activity (0.57 ± 0.27 µmol/L wb/hr) and all were confirmed to have the GLA IVS4 + 919G > A mutation. FD patients presented with heart failure (n = 5), heart block (n = 2), ventricular tachycardia (n = 1), chest pain (n = 3), and/or murmur (n = 1). Uncontrolled hypertension (n = 4) and/or severe mitral/aortic valve pathology (n = 2) were frequent. Ethnic subgroups included Teochew (n = 5), Canton (n = 2), and Wenzhou (n = 1). Endomyocardial biopsy (n = 6) revealed hypertrophic myocytes with vacuolization and dense lamellar bodies. Late-onset IVS4 + 919G > A FD is prevalent among Chinese LVH patients, and should be considered as a cause of LVH in adult patients even when hypertension and/or valve pathology are present.

Screening for Fabry Disease in patients with unexplained left ventricular hypertrophy.

Fabry Disease (FD) is a systemic disorder that can result in cardiovascular, renal, and neurovascular disease leading to reduced life expectancy. FD should be considered in the differential of all patients with unexplained left ventricular hypertrophy (LVH). We therefore performed a prospective screening study in Edmonton and Hong Kong using Dried Blood Spot (DBS) testing on patients with undiagnosed LVH. Participants found to have unexplained LVH on echocardiography were invited to participate and subsequently subjected to DBS testing. DBS testing was used to measure α-galactosidase (α-GAL) enzyme activity and for mutation analysis of the α-galactosidase (GLA) gene, both of which are required to make a diagnosis of FD. DBS testing was performed as a screening tool on patients (n = 266) in Edmonton and Hong Kong, allowing for detection of five patients with FD (2% prevalence of FD) and one patient with hydroxychloroquine-induced phenocopy. Left ventricular mass index (LVMI) by GLA genotype showed a higher LVMI in patients with IVS4 + 919G > A mutations compared to those without the mutation. Two patients were initiated on ERT and hydroxychloroquine was discontinued in the patient with a phenocopy of FD. Overall, we detected FD in 2% of our screening cohort using DBS testing as an effective and easy to administer screening tool in patients with unexplained LVH. Utilizing DBS testing to screen for FD in patients with otherwise undiagnosed LVH is clinically important due to the availability of effective therapies and the value of cascade screening in extended families.

Effect of N-acetylcysteine for prevention of contrast nephropathy in patients with moderate to severe renal insufficiency: a randomized trial.

BACKGROUND: The effect of N-acetylcysteine (NAC) to prevent contrast nephropathy (CN) in patients with moderate to severe renal insufficiency undergoing coronary angiography or interventions is not clear. METHODS: This is a prospective, open-label, randomized, controlled trial. Ninety-one consecutive patients with a serum creatinine level of 1.69 to 4.52 mg/dL (149 to 400 micromol/L) undergoing coronary procedures were recruited and randomly assigned to administration of either oral NAC, 400 mg, thrice daily the day before and day of the contrast procedure (the NAC group) or no drug (the control group). Serum creatinine was measured before and 48 hours after contrast exposure. The primary end point of this study was the development of CN, defined as an increase in serum creatinine concentration of 0.5 mg/dL or greater (> or =44 micromol/L) or a reduction in estimated glomerular filtration rate (GFR) of 25% or greater of the baseline value 48 hours after the procedure. RESULTS: There were no significant differences between the 2 groups (46 patients, NAC group; 45 patients, control group) in baseline characteristics or mean volume of contrast agent administered. Six patients (13.3%) in the control group and 8 patients (17.4%) in the NAC group developed CN (P = 0.8). Serum creatinine levels increased from 2.27 +/- 0.54 to 2.45 +/- 0.65 mg/dL (201 +/- 48 to 217 +/- 57 micromol/L; P = 0.003) in the NAC group and 2.37 +/- 0.61 to 2.40 +/- 0.70 mg/dL (210 +/- 54 to 212 +/- 62 micromol/L; P = 0.6) in the control group. The increase in serum creatinine levels between the 2 groups had no difference (P = 0.7). Estimated GFR decreased from 30.3 +/- 8.4 to 28.1 +/- 8.4 mL/min (P = 0.01) in the NAC group and 28.4 +/- 8.6 to 27.5 +/- 8.8 mL/min (P = 0.3) in the control group. The decline in estimated GFR between the 2 groups had no difference (P = 0.7). CONCLUSION: In the current study, oral NAC had no effect on the prevention of CN in patents with moderate to severe renal insufficiency undergoing coronary angiography or interventions. However, the sample size of our present study is small. Our findings highlight the need for a large-scale, randomized, controlled trial to determine the exact beneficial effect of NAC.