Alert!Heart involvement is the main cause of death

2022-04-25 0 By

Introduction Fabry’s disease is a rare genetic disease involving multiple organs and systems.Kidney, heart and brain are the main organs involved in the late stage of Fabry disease (1), and cardiovascular disease is the leading cause of fabry disease-related death (2).Studies have shown that 40%-60% of patients with fabry’s disease will have cardiac involvement 3, mainly manifested as left ventricular hypertrophy (LVH), and prone to fibrosis, arrhythmia, coronary microvascular dysfunction, valvular infiltration, and heart failure 1.Cardiac management of fabry disease requires specific interventions, including enzyme replacement therapy (ERT) and more comprehensive management of cardiac complications 5.The pathophysiological mechanism of cardiac involvement in Fabry’s disease trihexaloylsphenolol (GL-3) accumulates in cardiac tissue cells, cardiomyocytes, valvular fibroblasts, cardiac conduction system, and endothelial cells, leading to the clinical consequences shown in Figure 1.Increased concentration of its derivative, deacetylated GL-3 (Lyso-GL-3), and proliferation of vascular smooth muscle cells can lead to myocardial hypertrophy.Abnormal myocardial and endothelial cell function precedes the clinical presentation.As a result, disease-specific treatments are more effective at an early stage.4FIG. 1 Pathophysiological mechanism of heart injury caused by Fabry’s disease Diagnosis and Monitoring recommendations for Fabry’s disease Cardiac Disease Diagnosis and Monitoring In 2020, the expert consensus on cardiovascular management of Fabry’s disease released by foreign cardiovascular related expert groups, and the recommended diagnosis and monitoring of heart disease are shown in Table 15: Table 1.Heart disease diagnosis and monitoring recommendations for Fabry disease In China, the monitoring content of heart involvement is recommended: blood pressure and heart rate (at each visit);Electrocardiogram and echocardiogram (once a year);48h ELECTROcardiogram (increase or decrease frequency per year, or according to other risk factors such as age;If arrhythmia occurs, monitoring frequency should be increased);Cardiac magnetic resonance imaging gadolinium (once every 2 years, or monitored when there is evidence of disease progression);Cardiac troponin T, cardiac troponin I, and n-terminal brain natriuretic peptide precursors (at least once a year if accompanied by cardiomyopathy or bradycardia)1.Treatment of heart involvement in Fabry’s disease The treatment goals of fabry’s disease are to delay disease progression, improve quality of life, reduce the incidence of related complications, and prolong patient survival1.Heart failure and fatal ventricular arrhythmias are the main cardiac complications of fabre patients.LVH and fibrosis are particularly harmful to heart health, and their management can have a significant impact on morbidity and mortality. Cardiac treatment goals for fabre patients are shown in Table 23.Table 2. 2018 European consensus: Heart treatment targets for patients with Fabry-Bray disease Symptomatic therapy Bray disease involves multiple tissues and organs, and symptomatic treatment is mainly targeted at each organ involved.β -blockers should be used with caution and amiodarone should be avoided;• Consider using a pacemaker if bradycardia or evident atrioventricular block is present;• If symptoms of atrial fibrillation occur, anticoagulant therapy should be initiated and amiodarone should be avoided;• When considering the use of implantable cardioverter defibrillators if symptoms of malignant arrhythmias are present, note that it is not appropriate to manage Fabry’s disease by symptomatic treatment alone, which does not address the underlying pathogenesis of Fabry’s disease.Specific therapy Currently approved specific therapies for Fabry’s disease include ERT and molecular chaperone therapy.ERT by exogenous supplement gene recombinant α galactoside A (α Gal A), replace the patient’s enzyme activity is reduced or completely lack of α Gal A, promote the decomposition of GL 3, reduce GL 3 and Lyso GL 3 in the storage of organs and tissues, reduce the pain of patients, reduce proteinuria, and improve other corresponding symptoms,Prevent or delay the occurrence of multi-system diseases.Early initiation of ERT significantly improved patient outcomes, including cardiac outcomes 1.Agatase α is a human enzyme replacement therapy drug approved in China, which is produced 6,7 in continuous culture of transgenic human fibroblasts by gene activation technology.Long-term treatment with agatase α stabilizes or improves cardiac symptoms.The median value of LVMI (Q1,Q3) at baseline was 49.3 (37.7,65.4) g/m2.7 in the FOS study (n=580). The annual change rate of LVMI (±SE) in the agatase α group was +0.4 (0.08) g/m2.7, showing a slight increase.It is suggested that long-term treatment with agatase α can stabilize cardiac function in patients with fabre disease (Figure 2) 8.Figure 2. Estimation of the mean slope of LVMI over time in the 20-year follow-up cohort of cardiac function assessment Conclusion The heart is the engine of human life, and fabry disease heart involvement is undoubtedly worse for patients.Early initiation of ERT significantly improved cardiac outcome 1.The long-term cardiac benefits of agatase α provide a new therapeutic option for patients with fabre disease 8.1. Expert cooperation group of Fabry disease in China.Chinese Journal of Internal Medicine. 2021;Hung CL, et al. Acta Cardiol Sin. 2021; 60(4):321-330.2.Wanner C, Et al. Mol Genet Metab. 2018; 37(4):337-354.3.124:189 — 203.4. Hagege A, et al. Arch CardiovascDis. 2019;112(4):278-287.5.Linhart A, et al. Eur J Heart Fail.2020;22(7):1076-1096.6.Garman SC, et al. J Mol Biol.2004;2.Beck M, et al.Molecular Genetics and Metabolism. 2021;132(2):S19. Approval Number: VV-MedMAT-61007 Approval Date: 1/27/2022 Expiration date: 1/27/2024 Disclaima: This information is intended to help healthcare professionals better understand the latest advances in the field of disease.The platform does not agree with the description and views of the published information, but only provides more information.If any copyright problem is involved, please contact us and we will deal with it as soon as possible.Intended for use by healthcare professionals for informational purposes only.Such information is not in any way a substitute for professional medical guidance and should not be regarded as medical advice.If such information is used for purposes other than understanding the information, the platform and the author are not liable.END