Cardiac performance during exercise in patients with Fabry's disease (original) (raw)
Related papers
American journal of medical genetics. Part A, 2018
The cardiopulmonary exercise test (CPET) is a valuable tool to assess a patient's aerobic fitness and cardiac function, including the response to stress. There have been few studies using CPET to evaluate cardiopulmonary exercise capacity in patients with Fabry disease. We performed a retrospective chart review of patients with Fabry disease from 2001 to 2016, compared to age, gender, and size-matched normal controls. A total of 18 patients were evaluated using the Bruce protocol (treadmill) and 11 patients were evaluated with the ramp protocol (cycle ergometer). The Fabry group demonstrated significantly lower heart rate at peak exercise (151.2 ± 22.5 vs. 178.6 ± 16.2, p < .05), max indexed VO (23.7 ± 7 vs. 33.9 ± 8.4, p < .05), and peak index oxygen pulse (12.1 ± 3 vs. 15.2 ± 4.2, p < .05). When the groups were further separated into treadmill or cycle ergometry testing only, there remained statistically significant differences in peak indexed oxygen pulse, heart rate...
Cardiac and skeletal myopathy in Fabry disease: a clinicopathologic correlative study
Human Pathology, 2012
Skeletal muscle disturbances are commonly reported in patients with Fabry disease. Whether they derive from cardiac dysfunction or direct muscle involvement is still unclear. Clinical, noninvasive, and invasive cardiac and muscle studies, including an endomyocardial and muscle biopsy, were obtained in 12 patients (mean age, 42.1 ± 12.6 years; range, 24-58 years) with Fabry disease. In the youngest patients (group A, 4 men aged b35 years), results of cardiac and skeletal noninvasive studies were normal, except for reduced velocities in tissue Doppler imaging. Histologic examination indicated that muscle myocytes were unaffected, whereas muscle vessels showed the presence of mild glycosphingolipid accumulation in endothelial and smooth muscle cells. In the heart, cardiomyocytes and endothelial and smooth muscle cells of intramural cardiac vessels were involved by the disease. The oldest patients (group B, 6 men and 2 women aged N35 years) showed ultrasound muscle disarray and electromyography signs of myopathy, increased left ventricular mass, and normal cardiac function. Histologic examination showed that muscle myocytes contained mild glycosphingolipid accumulation compared with severe engulfment of cardiomyocytes. Moreover, similar infiltration of myocardial and muscle intramural vessels, causing lumen narrowing and fibrofatty tissue replacement, was observed. Direct muscle involvement occurs in patients with Fabry disease. It is milder and delayed compared with that in the heart. The difference in organ function and the need of residual α-galactosidase A activity are the likely causes.
Cardiovascular Events in Patients With Fabry Disease
Journal of the American College of Cardiology, 2011
These analyses were designed to determine the incidence of major cardiovascular (CV) events and the natural history of CV complications in patients with Fabry disease.
Cardiovascular Manifestations in Fabry Disease: A Clinical and Echocardiographic Study
Heart, Lung and Circulation, 2007
This study reviews the clinical and echocardiographic findings in a cohort of Fabry patients (n = 12) and compares echocardiographic findings to normal controls. Almost all patients had extracardiac manifestations. Five out of 12 patients had cardiovascular symptoms. Nine out of 12 patients had left ventricular hypertrophy (LVH) on the electrocardiogram (ECG) and one patient had short PR interval. Three patients had epicardial coronary disease. Four patients had 'rattail' appearance on left ventriculogram. Six patients who had myocardial biopsy showed extensive vacuolation of the myocytes on light microscopy and concentric, myelinoid lamellar cytoplasmic inclusion bodies on electron microscopy. On echocardiography, LV mass was significantly increased in the Fabry group compared to normal controls. Traditional parameters of diastolic function including peak E velocity, peak A velocity and deceleration time were no different to normal controls. The IVRT was significantly prolonged in the Fabry subjects. The PV atrial reversal duration exceeded that of mitral A wave duration in the Fabry group. The septal E velocity with Doppler tissue imaging (DTI) was significantly lower in the Fabry group than the normal controls. Fabry disease should be considered in the differential diagnosis in patients with unexplained LVH and late onset hypertrophic cardiomyopathy. Extracardiac manifestations are common.
Current status of cardiac manifestations in Fabry disease and their treatment
2021
In the present paper, we discuss cardiac symptoms in Fabry patients, the main imaging and laboratory methods to diagnose myocardial involvement in this disease. In the second part, we present the main treatment options in Fabry patients, including enzyme replacement therapy, substrate reduction treatment, chaperone therapy, gene treatment.
The right ventricle in Fabry disease
Acta Paediatrica, 2007
Left ventricular (LV) hypertrophy is a common feature in Fabry disease-related progressive infiltrative hypertrophic cardiomyopathy and affects both men and women, but at different ages. To date, however, little is known about the role of right ventricular (RV) function in Fabry disease. Therefore, this study aimed to investigate the extent of RV involvement in patients with Fabry disease. Echocardiographic examination of the right and left ventricle was carried out in 129 patients (80 women and 49 men) with Fabry disease. RV hypertrophy was present in 46 patients (35.7%). Of these patients, 13 showed signs of severely depressed right systolic function (tricuspid annulus movement &amp;lt; 10 mm and a prolonged RV pre-ejection period/pulmonary ejection time ratio) and six patients showed additional severe depression of parameters of diastolic function (pseudo-normal or restrictive RV filling pattems). Those patients with RV hypertrophy and severely compromised systolic and diastolic function had the highest LV masses (92 +/- 11.7 g/m(2.7)). RV involvement is common in Fabry disease and ultimately progresses to severe systolic and diastolic RV dysfunction. These findings might explain why patients with preserved LV function can develop clinical features such as reduced exercise capacity, organomegaly and lymphoedema.
Cardiac involvement in genotype-positive Fabry disease patients assessed by cardiovascular MR
Heart, 2016
Cardiac magnetic resonance (CMR) has the potential to provide early detection of cardiac involvement in Fabry disease. We aimed to gain further insight into this by assessing a cohort of Fabry patients using CMR. Fifty genotype-positive Fabry subjects (age 45±2 years; 50% male) referred for CMR and 39 matched controls (age 40±2 years; 59% male) were recruited. Patients had a mean Mainz severity score index of 15±2 (range 0-46), reflecting an overall mild degree of disease severity. Compared with controls, Fabry subjects had a 34% greater left ventricular mass (LVM) index (82±5 vs 61±2 g/m(2), p=0.001) and had a significantly greater papillary muscle contribution to total LVM (13±1 vs 6±0.5%, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001), even in the absence of left ventricular hypertrophy (LVH). Late gadolinium enhancement (LGE) was present in 15 Fabry subjects (9/21 males and 6/23 females). The most common site for LGE was the basal inferolateral wall (93%, 14/15). There was a positive association between LVM index and LGE. Despite this, there were two males and three females with no LVH that displayed LGE. Of Fabry subjects who were not on enzyme replacement therapy at enrolment (n=28), six were reclassified as having cardiac involvement (four LVH-negative/LGE-positive, one LVH-positive/LGE-positive and one LVH-positive/LGE-negative). CMR was able to detect cardiac involvement in 48% of this Fabry cohort, despite the overall mild disease phenotype of the cohort. Of those not on ERT, 21% were reclassified as having cardiac involvement allowing improved risk stratification and targeting of therapy.
Cardiac and Vascular Hypertrophy in Fabry Disease
Arteriosclerosis, Thrombosis, and Vascular Biology, 2006
Objectives— Fabry disease is an X-linked disorder resulting from α-galactosidase A deficiency. The cardiovascular findings include left ventricular hypertrophy (LVH) and increased intima-media thickness of the common carotid artery (CCA IMT). The current study examined the possible correlation between these parameters. To corroborate these clinical findings in vitro, plasma from Fabry patients was tested for possible proliferative effect on rat vascular smooth muscle cells (vascular smooth muscle cell [VSMC]) and mouse neonatal cardiomyocytes. Methods and Results— Thirty male and 38 female patients were enrolled. LVH was found in 60% of men and 39% of women. Increased CCA IMT was equally present in males and females. There was a strong positive correlation between LV mass and CCA IMT (r 2 =0.27; P <0.0001). VSMC and neonatal cardiomyocyte proliferative response in vitro correlated with CCA IMT (r 2 =0.39; P <0.0004) and LV mass index (r 2 =0.19; P =0.028), respectively. Conclu...