Unexpectedly High Prevalence of Coronary Spastic Angina in Patients With Anderson-Fabry Disease

Kitani, Yuya; Nakagawa, Naoki; Naka, Sadahiro; Takeuchi, Toshiharu; Takahashi, Fumiyuki; Momosaki, Ken; Nakamura, Kimitoshi; Endo, Fumio; Maruyama, Haruhiko; Hasebe, Naoyuki

doi:10.1253/circj.cj-18-0734

Cited by 16 publications

(6 citation statements)

References 12 publications

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“…Besides coronary microvascular dysfunction, coronary vasospasm may also contribute to angina [ 131 , 132 ] and may precipitate dysrhythmias and sudden death [ 133 ].…”

Section: Cardiac Manifestations Of Fdmentioning

confidence: 99%

Fabry Disease and the Heart: A Comprehensive Review

Azevedo

Cordeiro

Gago

et al. 2021

IJMS

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Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.

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“…Besides coronary microvascular dysfunction, coronary vasospasm may also contribute to angina [ 131 , 132 ] and may precipitate dysrhythmias and sudden death [ 133 ].…”

Section: Cardiac Manifestations Of Fdmentioning

confidence: 99%

Fabry Disease and the Heart: A Comprehensive Review

Azevedo

Cordeiro

Gago

et al. 2021

IJMS

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“…One of those three patients with cerebral lacunar infarction (Patient 3) was complicated by coronary spastic angina. We recently reported that the prevalence of coronary spastic angina complicated by FD was high ( 22 , 23 ). Although it is difficult to prove a causal relationship, given the possibility that ischemic stroke is also associated with vasospasm, vascular vasospasm may be a common and important pathophysiological mechanism underlying damage in various organs.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Neurological Symptoms in Adult Japanese Patients with Fabry Disease

et al. 2021

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Objective Fabry disease (FD) is a hereditary lysosomal storage disease that has been highlighted as a possible etiology of stroke at a young age and presents with other various neurological symptoms. Since FD is rare, limited information is currently available on the prevalence of neurological symptoms in Japanese patients with FD. Therefore, we examined the characteristics of neurological symptoms and brain magnetic resonance imaging (MRI) findings in adult Japanese patients with FD. Methods This was a retrospective, single-center study. We reviewed neurological symptoms and brain MRI findings in the medical records of 12 adult Japanese patients with FD diagnosed by a gene analysis of the αgalactosidase gene. Results Ten out of 12 patients with FD presented with the following neurological symptoms: acroparesthesia (n=6), headache (n=5) [migraine (n=4)], hypohidrosis (n=5), and cerebral infarction (n=3). Two and three of the patients with migraine were complicated by ischemic stroke and coronary spastic angina, respectively. Five and 10 patients presented with periventricular hyperintensity and deep white matter hyperintensity, respectively, on brain MRI. Two out of eight patients had cerebral microbleeds. Seven out of 11 patients had a dilated basilar artery diameter on magnetic resonance angiography. There were no patients with the pulvinar hyperintensity sign. Conclusion Patients with FD present with various neurological symptoms. Headache, particularly migraine, might be a major neurological symptom in patients with FD. Since migraine, ischemic stroke, and coronary spastic angina might occur together in FD, caution is needed when administering triptan to FD patients with migraine.

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“…In this report by Kitani et al, 8 AFD patients complicated with CSA were treated with anti-anginal agents and galactosidase enzyme replacement therapy (ERT). 4 The relief of angina was fairly attained; 6 of 8 patients were free from angina. Thurberg et al reported that ERT could clear microvascular endothelial Gb3 deposits in the kidney.…”

Section: Clinical Perspectivesmentioning

confidence: 93%

Unexpected, But Reasonable Association Between Anderson-Fabry Disease and Coronary Vasospasm

Matoba

Nakano

Tsutsui

2019

Circ J

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nderson-Fabry disease (AFD) is an X-linked lysosomal storage disease caused by a loss-of-function mutation in the lysosomal enzyme α-galactosidase A (GLA) gene, resulting in progressive intracellular accumulation of neutral glycosphingolipids, particularly globotriaosylceramid (Gb3), in different tissues including skin, kidney, central and peripheral nervous systems, and the heart. 1 Patients with AFD suffer from various cardiac complications, including hypertrophic cardiomyopathy, valvular diseases, conduction defects and arrhythmias, as well as coronary artery stenosis, caused by Gb3 accumulation in vascular endothelial and smooth muscle cells (VSMCs) (Figure); 2,3 however, the prevalence of coronary spastic angina (CSA) has not been clearly demonstrated among AFD patients previously. In this issue of the Journal, Kitani et al 4 describe the clinical presentations and results of intracoronary acetylcholine provocation test 5 in 9 consecutive patients with AFD. They found a high prevalence (8/9 patients) of acetylcholine-induced CSA without coronary artery stenosis. 4 It should be noted that all 9 patients complained of angina at rest, 4 which suggests possible self-selection bias to undergo cardiac assessment, and therefore, raises prior probability of a positive diagnosis of CSA even among consecutive AFD patients. Nonetheless, this report is the first to describe a high prevalence of CSA in a series of Japanese patients with AFD. Interestingly, 6 of the 8 acetylcholine-positive patients were female in this study, 4 in contrast to the fact that as low as 13% of Japanese CSA patients are female. 5 However, the significance of either sex or ethnicity in the prevalence of CSA was indeterminate in this study. Endothelial Dysfunction in AFD Vascular endothelial cells produce endothelium-derived relaxing factors (EDRFs), including prostanoids, nitric oxide (NO) and endothelium-derived hyperpolarizing factor, and orchestrate VSMCs to regulate vascular tonus and blood flow. 6 CSA is a result of endothelial dysfunction, or VSMC hypercontractility, or both. 5 Several reports have described an altered NO pathway in AFD. Moore et al reported that enhanced nitrotyrosine staining was observed in dermal and cerebral blood vessels by immunohistochemical analysis, which indicates dysregulated NO production as well as reactive oxygen species (ROS) Article p 481 The opinions expressed in this article are not necessarily those of the editors or of the Japanese Circulation Society.

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Unexpectedly High Prevalence of Coronary Spastic Angina in Patients With Anderson-Fabry Disease

Cited by 16 publications

References 12 publications

Fabry Disease and the Heart: A Comprehensive Review

Fabry Disease and the Heart: A Comprehensive Review

Characteristics of Neurological Symptoms in Adult Japanese Patients with Fabry Disease

Unexpected, But Reasonable Association Between Anderson-Fabry Disease and Coronary Vasospasm

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