825 Regression of left ventricular hypertrophy in patients with fabry cardiomyopathy during long term enzyme replacement therapy - the impact of the baseline conditions

Abstract Background Fabry disease (FD) is X-linked genetic disorder caused by the deficiency or absent activity of lysosomal α- galactosidase. When the heart is involved, progressive left ventricular hypertrophy (LVH) is the key feature. Although, LVH is not present in all subjects, some of them progress with LVH despite enzyme replacement therapy (ERT). The present study aimed to evaluate the characteristics of patient of FD without overt LVH, but progresses with their left ventricular mass index (LVMI). Method : This study includes subjects carrying genetic mutations for FD without LVH (n = 12) in a single tertiary center. ‘Decreasing LVMI group (Group1)’ was defined when pre-ERT LVMI minus last LVMI value obtained by echocardiography was positive, and when negative, defined as ‘Increasing LVMI group (Group 2)’. The baseline characteristics and echocardiographic parameters including global strain was analyzed. Result : Total 6 patients were classified as Group 1 and 2 each. The median age at diagnosis for male was 21 vs 27 for each group, and 21 vs 31 for female. The median follow-up duration was 4.0 vs 5.7 yr. The antibody formation for replaced enzyme was 3 for Group 2 and any family member who developed overt LVH was much 1 vs 3 for group 1 vs 2. Initial 3 plane GLS was worse and showed trend to drop in Group 2. Conclusion : In the Fabry patients get worse with their LVMI but still not developed overt LVH despite enzyme replacement therapy, there are some clinical and echo-parameter difference. These findings could suggest insufficient enzyme replacement therapy. Group 1 (n = 6) Group 2 (n = 6) Female/Male 4/2 3/3 Age of at Dx (Female) (median) 21 28 Age of at Dx (Male) (median) 21 31 F/U duration (median) 4.0 yrs 5.7 yrs Antibody formation 0 3 Any Overt LVH family Genotype c.56T > C c.40-11T > A, 782_delG, c.658C > T Initial LVMI (Median) 98.2g/m2 70.9g/m2 Initial GLS (3P) -19 -17.8 Continuously elevated LysoGb3 2 4 Proteinuria >300mg 1 3 (1 preparing HD)

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Fabry Disease and the Effectiveness of Enzyme Replacement Therapy (ERT) in Left Ventricular Hypertrophy (LVH) Improvement: A Review and Meta-Analysis

International Journal of Medical Sciences ◽

10.7150/ijms.66448 ◽

2022 ◽

Vol 19 (1) ◽

pp. 126-131

Author(s):

Chung-Lin Lee ◽

Shuan-Pei Lin ◽

Dau-Ming Niu ◽

Hsiang-Yu Lin

Keyword(s):

Left Ventricular Hypertrophy ◽

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Ventricular Hypertrophy ◽

Meta Analysis ◽

Left Ventricular ◽

Enzyme Replacement

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P0067PREDICTORS OF LONG-TERM OUTCOME IN A SPANISH COHORT OF PATIENTS WITH FABRY DISEASE ON ENZYME REPLACEMENT THERAPY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0067 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Marian Goicoechea ◽

Francisco Gomez-Preciado ◽

Silvia Benito ◽

Joan Torras ◽

Roser Torra ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Replacement Therapy ◽

Left Ventricular ◽

Response To Therapy ◽

Clinical Event ◽

Enzyme Replacement ◽

Clinical Events ◽

The Impact

Abstract Background and Aims Fabry disease may be treated by enzyme replacement therapy (ERT), but the impact of chronic kidney disease (CKD) on the response to therapy remains unclear. The aim of the present study was to analyse the incidence and predictors of clinical events in Fabry disease patients on ERT. Method Multicentre retrospective observational analysis of patients diagnosed and treated with ERT for Fabry disease. The primary outcome was the first renal, neurological or cardiological events or death during a follow-up of 60 months (24-120). Results In 69 patients (42 males, 27 females, mean age 44.6 ±13.7 years), at the end of follow-up, eGFR and the left ventricular septum thickness remained stable and the urinary albumin: creatinine ratio tended to decrease, but this decrease only approached significance in patients on agalsidase-beta (242 to 128 mg/g (p = 0.05). At the end of follow-up, 21 (30%) patients had suffered an incident clinical event: 6 renal, 2 neurological and 13 cardiological (including 3 deaths). Events were more frequent in patients with baseline eGFR ≤60 ml/min/1.73 m2 (log Rank 12.423, p=0.001), and this remained significant even after excluding incident renal events (log Rank 4.086, p=0.043), being these differences more relevant in females (log Rank 18.514, p<0.001) than males (logRank: 3.442, p=0.064). Lower baseline eGFR was associated with a 3- to 7-fold increase in the risk of clinical events in different Cox models. Conclusion GFR at the initiation of ERT is the main predictor of clinical events, both in males and in females, suggesting that start of ERT prior to the development of CKD is associated with better outcomes. For the first time, we show that initiation of ERT in women before renal function deteriorates has a similar or even larger impact as in Fabry males to prevent clinical events.

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Fabry Disease

10.1093/med/9780199972135.003.0049 ◽

2016 ◽

Author(s):

Michael West ◽

Gabor Linthorst

Keyword(s):

Natural History ◽

Left Ventricular Hypertrophy ◽

Enzyme Replacement Therapy ◽

Fabry Disease ◽

Patient Outcomes ◽

Ventricular Hypertrophy ◽

Unknown Origin ◽

Left Ventricular ◽

Enzyme Replacement ◽

Modest Effect

Fabry disease was initially believed to be a very rare disorder, but an increase in prevalence following screening studies revealed that it may be more frequent in a less severe (nonclassical) variant. The adult physician can encounter both phenotypes: classical disease arising in childhood, or after establishing the diagnosis in an adult male. The nonclassical phenotype is usually diagnosed after additional investigations in a patient with renal disease or left ventricular hypertrophy (LVH) of unknown origin. Enzyme replacement therapy (ERT) appears to have a modest effect in Fabry disease, and many challenges remain both in understanding the pathophysiology and natural history as well as in improving patient outcomes.

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The impact of left ventricular hypertrophy on early and long-term survival after coronary artery bypass grafting

International Journal of Cardiology ◽

10.1016/j.ijcard.2008.03.013 ◽

2009 ◽

Vol 135 (1) ◽

pp. 36-42 ◽

Cited By ~ 2

Author(s):

Ioannis K. Toumpoulis ◽

Themistocles P. Chamogeorgakis ◽

Dimitrios C. Angouras ◽

Daniel G. Swistel ◽

Constantine E. Anagnostopoulos ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Artery Bypass Grafting ◽

Left Ventricular Hypertrophy ◽

Ventricular Hypertrophy ◽

Artery Bypass ◽

Left Ventricular ◽

Bypass Grafting ◽

Term Survival ◽

The Impact

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Characteristics of the Electrocardiogram in Japanese Fabry Patients Under Long-Term Enzyme Replacement Therapy

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2020.614129 ◽

2021 ◽

Vol 7 ◽

Author(s):

Satoshi Morimoto ◽

Ayumi Nojiri ◽

Eiko Fukuro ◽

Ikuko Anan ◽

Makoto Kawai ◽

...

Keyword(s):

Enzyme Replacement Therapy ◽

Replacement Therapy ◽

Left Ventricular ◽

Classical Type ◽

Female Patients ◽

Enzyme Replacement ◽

Strain Pattern ◽

Qrs Duration ◽

Male Patients

Objective: An electrocardiogram (ECG) is an important tool for demonstrating cardiac manifestations in various heart diseases. The present study clarified the characteristics of ECG parameters in Japanese Fabry patients under long-term enzyme replacement therapy (ERT).Methods: We analyzed the ECGs of 40 Fabry patients (male, n = 17; female, n = 23) before and after treatment with ERT. To evaluate the atrio-ventricular conduction, the PQ interval, corrected PQ and PQ minus P-wave in lead II (Pend-Q) were calculated. The QRS duration, QTc, Sokolow-Lyon index, and strain pattern were also examined.Results: At the baseline, the shortening of the PQ interval, corrected PQ and Pend-Q was identified in 7.5, 25.0, and 47.5% of cases, respectively. The prolongation of QRS duration and QTc was found in 7.5 and 40.0% of cases, respectively. The strain pattern was mainly identified in female patients, irrespective of left ventricular hypertrophy (LVH). During long-term ERT, the PQ interval, corrected PQ and Pend-Q did not change significantly. The QRS duration was significantly prolonged in both genders, whereas the QTc was significantly prolonged only in male patients. A subgroup analysis revealed that the prolongation of the QRS duration and QTc only occurred in male patients with LVH and only occurred in female patients with the classical type mutation. The prevalence of the strain was significantly increased only in male patients with LVH.Conclusions: These results suggest that the shortening of the Pend-Q is a specific finding in Japanese Fabry patients, and the strain pattern without LVH in female patients can be considered Fabry disease. During long-term ERT, prolongation of the QRS duration and QTc can indicate the progression of myocardial damage in male patients with LVH and in female patients with the classical type mutation.

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