Diagnosis and treatment of the cardiovascular consequences of Fabry disease

Baig, Shanat; Vijapurapu, Ravi; Alharbi, Fahad J.; Nordin, Sabrina; Kozor, Rebecca; Moon, James; Bembi, Bruno; Geberhiwot, Tarekegn; Steeds, Richard P.

doi:10.1093/qjmed/hcy120

Cited by 13 publications

(10 citation statements)

References 38 publications

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“…The main aim of treatment in FD is to minimise end-organ damage. While there is no evidence specifically in FD patients, it is widely accepted that aggressive management of conventional risk factors for atherosclerosis (including lipid lowering therapy, tight control of hypertension and good glycemic control) should be encouraged as well as smoking cessation and regular physical exercise [ 55 ]. Aggressive blood pressure control may reduce progression of LVH and use of angiotensin converting (ACE) inhibitors are often used due to renal dysfunction in FD [ 56 ].…”

Section: Treatment Of Angina In Fdmentioning

confidence: 99%

Atherosclerosis in Fabry Disease—A Contemporary Review

Roy

Umar

Ochoa-Ferraro

et al. 2021

JCM

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Fabry disease (FD) is a lysosomal storage disorder characterised by a deficiency in the enzyme α-galactosidase A resulting in sphingolipid deposition which causes progressive cardiac, renal, and cerebral manifestations. The case illustrates a patient with FD who died suddenly, and medical examination demonstrated myocardial scarring and prior infarction. Angina is a frequent symptom in FD. Our own data are consistent with registry data indicating a high prevalence of risk factors for coronary artery disease (CAD) in FD that may accelerate conventional atherosclerosis. Patients with FD also have a higher high-density lipoprotein (HDL)/total cholesterol (T-Chol) ratio which may further accelerate atherosclerosis through expression of early atherosclerotic markers. Patients with FD may develop CAD both via classical atherosclerosis and through formation of thickened fibrocellular intima containing fibroblasts with storage of sphingolipids. Both mechanisms occurring together may accelerate coronary stenosis, as well as alter myocardial blood flow. Our data supports limited data that, although coronary flow may be reduced, the prevalence of epicardial coronary stenosis is low in FD. Microvascular dysfunction and arterial wall stress from sphingolipid deposition may form reactive oxygen species (ROS) and myeloperoxidase (MPO), key atherosclerotic mediators. Reduced myocardial blood flow in FD has also been demonstrated using numerous imaging modalities suggesting perfusion mismatch. This review describes the above mechanisms in detail, highlighting the importance of modifying cardiovascular risk factors in FD patients who likely develop accelerated atherosclerosis compared to the general population.

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Section: Treatment Of Angina In Fdmentioning

confidence: 99%

Atherosclerosis in Fabry Disease—A Contemporary Review

Roy

Umar

Ochoa-Ferraro

et al. 2021

JCM

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“…Согласно данным регистров пациентов с БФ, у значительной части из них длительное время заболевание остается недиагностированным [3,4,7]. Ошибочные диагнозы и несвоевременная диагностика приводят к прогрессированию необратимых изменений в тканях [8,9].…”

Section: Discussionunclassified

“…Представленный клинический пример демонстрирует важность скрининга среди пациентов из групп риска, а также важность знания характерных симптомов, тщательного сбора анамнеза и настороженности врачей в отношении данного заболевания. Так, у пациентов с ГМЛЖ неясной этиологии целесообразно исключать БФ [8,9].…”

Section: Discussionunclassified

Diagnostics of Fabry disease in arrhythmology practice: a case report

et al. 2022

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Heart failure in Fabry disease (FD) is unfavorable prognostic manifestation and cause of death. Given that the disease is rare in clinical practice, the low awareness of physicians about this pathology leads to its late diagnosis and the lack of pathogenetic therapy.Aim. To present a clinical picture of the cardiovascular phenotype in FD in order to increase the awareness of doctors about this disease.Material and methods. In this clinical case, an asymptomatic FD course up to 46 years of age and mani festation in the form of arrhythmia were observed. According to echo car dio graphy, severe left ventricular hypertrophy (myocardial mass index, 214 g/m2) without signs of left ventricular (LV) outflow tract obstruction and left atrial (LA) dilatation were revealed (LA volume index — 47 ml/m2). Right ventricular (RV) and LV systolic function was assessed using two-dimensional speckletracking strain echocardiography. Latent subclinical RV and LV systolic dysfunction was established.Results. Tandem mass spectrometry revealed a sharp decrease in alphagalactosidase activity of 0,03 umol/L/h (norm range, 0,80-15,00 umol/L/h), as well as an in creased Lyso-GB3 concentration of 95,18 ng/ml (normal range, 0,05-3,0 ng/ ml). A molecular genetic study of blood samples was carried out. By direct automatic sequencing of the GLA gene, a variant of the c.1229 C>T nucleotide sequence was identified, leading to the replacement of p.Thr4101le in the hemizygous state.Conclusion. This case shows the possibility and expediency of diagnosing FD in cardiology practice in patients with LV myocardial hypertrophy of unclear etiology, while atypical variants can be diagnosed only by molecular genetic testing.

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“…у 34% мужчин и 57% женщин с установленным диагнозом [1]. Лежащий в основе БФ врожденный дефицит фермента α-галактозидазы А по мере своего прогрессирования приводит к первичному лизосомальному накоплению глоботриаозилсфингозина (Gb3); повреждение лизосом индуцирует каскад внутриклеточных реакций и механизмов, формирующих гипертрофию стенки левого желудочка (ГЛЖ) и необратимый фиброз миокарда [2]. При инструментальных исследованиях ГЛЖ обнаружи-существенно расширить возможности мониторинга ЭКГ.…”

Section: ключевые моменты что известно о предмете исследования?unclassified

Ambulatory electrocardiographic monitoring in patients with Fabry disease: study design and cohort characterization

Котельникова

Senchikhin

Lipchanskaya

2023

Cardiovasc Ther Prev

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Aim. To develop study design and analyze the characteristics of a cohort of patients with cardiac manifestations of Fabry disease (FD) in order to study the possibilities of electrocardiography (ECG) telemonitoring for screening for cardiac arrhythmias (CA), requiring a change in therapeutic tactics.Material and methods. This prospective cohort study included 11 patients (8 men and 3 women) with documented FD, with cardiac complaints and ECG signs of heart involvement. For ECG telemonitoring, non-invasive digital event recorders ECG Dongle (Nordavind-Dubna, Russia) were used. Primary endpoint was registration of CA requiring a change in therapeutic tactics (implantation of a pacemaker/defibrillator-cardioverter/prescribing anticoagulants). Secondary endpoint was dynamics of monitored parameters for operational correction of the therapeutic regimen.Results. The cohort of patients is predominantly male (73/27%; mean age, 41±13,7 years). At the time of inclusion, 8 (73%) patients received enzyme replacement therapy for 4-73 months. Most patients are active Internet users, are aware of telemedicine possibilities and are interested in remote monitoring. The main complaints were related to cardiac function interruptions, palpitations, and chest discomfort. Left ventricular hypertrophy was diagnosed on ECG in 7 (64%) patients. Echocardiography revealed symmetrical left ventricular hypertrophy in 5 patients, asymmetric interventricular septal hypertrophy in 2 patients. Other echocardiographic abnormalities included valvular heart disease (mitral and tricuspid valve prolapse with mitral and tricuspid regurgitation, presence of supplemental chords) and aortic root dilatation. Initially, the ECG was dominated by sinus rhythm (n=10); 1 patient had documented ventricular tachycardia, 4 patients had single and coupled ventricular premature contractions; supraventricular tachycardia and premature contractions in 2 patients. Four patients had a PR interval shortening without signs of accessory pathways, 1 patient — Wolff-Parkinson-White syndrome, 1 patient — prolonged QTc interval.Conclusion. For effective management of FD, additional multicenter studies are required to develop algorithms for making tactical decisions in the process of cardiac monitoring, taking into account the characteristics of the cardiovascular manifestations of this disease. The article proposes a technology for telemedicine cardiac monitoring using ECG event recorders for outpatient CA screening.

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Diagnosis and treatment of the cardiovascular consequences of Fabry disease

Cited by 13 publications

References 38 publications

Atherosclerosis in Fabry Disease—A Contemporary Review

Atherosclerosis in Fabry Disease—A Contemporary Review

Diagnostics of Fabry disease in arrhythmology practice: a case report

Ambulatory electrocardiographic monitoring in patients with Fabry disease: study design and cohort characterization

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