Burden of Valvular Heart Disease in Patients with Fabry Disease

Yogasundaram, Haran; Nikhanj, Anish; Chatur, Safia; Qi, Arthur; Hagen, Leanne; Bailey, Laurie; Khan, Aneal; Hopkin, Robert J.; Fine, Nowell M.; Jefferies, John L.; Oudit, Gavin Y.

doi:10.1016/j.echo.2021.09.013

Cited by 6 publications

(6 citation statements)

References 7 publications

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“…Sphingolipid accumulation in cardiac endothelial and smooth muscle cells is associated with endothelial dysfunction and small vessel ischemia. This is supported by the prevalent incidence of myocardial infarction, particularly in patients with LVH, despite the absence of obstructive coronary artery disease [ 38 , 39 ]. Beyond the mechanical and functional implications of sphingolipid deposition, emerging evidence suggests that alterations in energy metabolism, particularly altered mitochondrial function and imbalances in energy production, may play a role in the pathogenesis of FD [ 31 , 40 •].…”

Section: Fabry Cardiomyopathy: Clinical Perspective and Pathogenic Me...mentioning

confidence: 99%

Fabry Disease: Cardiac Implications and Molecular Mechanisms

Weissman,

Dudek,

Sequeira

et al. 2024

Curr Heart Fail Rep

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Purpose of Review This review explores the interplay among metabolic dysfunction, oxidative stress, inflammation, and fibrosis in Fabry disease, focusing on their potential implications for cardiac involvement. We aim to discuss the biochemical processes that operate in parallel to sphingolipid accumulation and contribute to disease pathogenesis, emphasizing the importance of a comprehensive understanding of these processes. Recent Findings Beyond sphingolipid accumulation, emerging studies have revealed that mitochondrial dysfunction, oxidative stress, and chronic inflammation could be significant contributors to Fabry disease and cardiac involvement. These factors promote cardiac remodeling and fibrosis and may predispose Fabry patients to conduction disturbances, ventricular arrhythmias, and heart failure. While current treatments, such as enzyme replacement therapy and pharmacological chaperones, address disease progression and symptoms, their effectiveness is limited. Summary Our review uncovers the potential relationships among metabolic disturbances, oxidative stress, inflammation, and fibrosis in Fabry disease–related cardiac complications. Current findings suggest that beyond sphingolipid accumulation, other mechanisms may significantly contribute to disease pathogenesis. This prompts the exploration of innovative therapeutic strategies and underscores the importance of a holistic approach to understanding and managing Fabry disease.

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Section: Fabry Cardiomyopathy: Clinical Perspective and Pathogenic Me...mentioning

confidence: 99%

Fabry Disease: Cardiac Implications and Molecular Mechanisms

Weissman,

Dudek,

Sequeira

et al. 2024

Curr Heart Fail Rep

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“…Indeed, the postmortem examination of Fabry hearts revealed that the greatest concentrations of glycosphingolipids were in the mitral valve ( 36 ). The most recent study revealed that in classic- FD, the prevalence of valvular disease, from moderate to severe, was 10%, with mitral and tricuspid regurgitation being the most common ( 37 , 38 ). Beyond the glycosphingolipids accumulation specifically at valvular levels, other phenomenon could be involved in FD valve dysfunction, including thickening of the sub-valvular apparatus ( 35 ) geometric distortion of the atria, valvular annulus, or aortic root dilatation ( 37 ).…”

Section: Exercise Intolerance and Fatigability In Fd Patientsmentioning

confidence: 99%

Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease

De Marco,

Gambardella,

Bianco

et al. 2024

Front. Cardiovasc. Med.

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Fabry disease (FD), also known as Anderson-Fabry disease, is a hereditary disorder of glycosphingolipid metabolism, caused by a deficiency of the lysosomal alpha-galactosidase A enzyme. This causes a progressive accumulation of glycosphingolipids in tissues and organs which represents the main pathogenetic mechanism of FD. The disease is progressive and multisystemic and is characterized by early symptoms and late complications (renal, cardiac and neurological dysfunction). Fatigue and exercise intolerance are early common symptoms in FD patients but the specific causes are still to be defined. In this narrative review, we deal with the contribution of cardiac and pulmonary dysfunctions in determining fatigue and exercise intolerance in FD patients.

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“…AFD is associated with the development of valvular stenosis and regurgitation, although valvular heart disease is generally uncommon. Regurgitant lesions are thought to develop due to glycosphingolipid deposition within the valve leaflets and sub-valvular apparatus, as well as geometric distortion of the atria, valvular annulus, or aortic root dilatation (64). In a contemporary study of predominantly classic-phenotype AFD (80%), the prevalence of moderate to severe valvular disease was 10%, with mitral and tricuspid regurgitation being the most common (64).…”

Section: Valvular and Aortic Diseasementioning

confidence: 99%

Anderson-Fabry disease cardiomyopathy: an update on epidemiology, diagnostic approach, management and monitoring strategies

Averbuch

White

Fine

2023

Front. Cardiovasc. Med.

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Anderson-Fabry disease (AFD) is an X-linked lysosomal storage disorder caused by deficient activity of the enzyme alpha-galactosidase. While AFD is recognized as a progressive multi-system disorder, infiltrative cardiomyopathy causing a number of cardiovascular manifestations is recognized as an important complication of this disease. AFD affects both men and women, although the clinical presentation typically varies by sex, with men presenting at a younger age with more neurologic and renal phenotype and women developing a later onset variant with more cardiovascular manifestations. AFD is an important cause of increased myocardial wall thickness, and advances in imaging, in particular cardiac magnetic resonance imaging and T1 mapping techniques, have improved the ability to identify this disease non-invasively. Diagnosis is confirmed by the presence of low alpha-galactosidase activity and identification of a mutation in the GLA gene. Enzyme replacement therapy remains the mainstay of disease modifying therapy, with two formulations currently approved. In addition, newer treatments such as oral chaperone therapy are now available for select patients, with a number of other investigational therapies in development. The availability of these therapies has significantly improved outcomes for AFD patients. Improved survival and the availability of multiple agents has presented new clinical dilemmas regarding disease monitoring and surveillance using clinical, imaging and laboratory biomarkers, in addition to improved approaches to managing cardiovascular risk factors and AFD complications. This review will provide an update on clinical recognition and diagnostic approaches including differentiation from other causes of increased ventricular wall thickness, in addition to modern strategies for management and follow-up.

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Burden of Valvular Heart Disease in Patients with Fabry Disease

Cited by 6 publications

References 7 publications

Fabry Disease: Cardiac Implications and Molecular Mechanisms

Fabry Disease: Cardiac Implications and Molecular Mechanisms

Cardiopulmonary determinants of reduced exercise tolerance in Fabry disease

Anderson-Fabry disease cardiomyopathy: an update on epidemiology, diagnostic approach, management and monitoring strategies

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