TY - JOUR

T1 - Echocardiographic and clinical findings in patients with Fabry disease during long-term enzyme replacement therapy

T2 - a nationwide Danish cohort study

AU - Madsen, Christoffer Valdorff

AU - Bundgaard, Henning

AU - Rasmussen, Åse Krogh

AU - Sørensen, Søren Schwartz

AU - Petersen, Jørgen Holm

AU - Køber, Lars

AU - Feldt-Rasmussen, Ulla

AU - Petri, Helle

PY - 2017

Y1 - 2017

N2 - OBJECTIVES: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT.METHODS: We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort. We followed clinical signs, symptoms and findings by echocardiography, electrocardiography and Holter-monitoring.RESULTS: We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0-12] years and 6 [0-13] years, respectively. Comparison between ERT and non-ERT receiving patients by left ventricular mass (echocardiographic assessment) and Sokolow-Lyon voltage- and Cornell product criteria (electrocardiographic assessment) revealed no significant differences. In the ERT group, we observed no change in left ventricular mass but a decrease in Sokolow-Lyon voltage- and Cornell product criteria from baseline to follow-up; 30 mm [15-53] vs. 25 mm [3-44], p < 0.005 and 1710 mm·ms [480-3740] vs. 1520 mm·ms [550-5740], p < .05, respectively. There were no changes within the non-ERT group. During follow-up, cardiac symptoms and use of cardiovascular procedures and -medication increased significantly in the ERT group, whereas no differences were observed within the non-ERT group.DISCUSSION: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research.

AB - OBJECTIVES: In patients with Fabry disease (FD), left ventricular hypertrophy and arrhythmias are frequently observed and cardiac involvement is the leading cause of death. Long-term efficacy of enzyme replacement therapy (ERT) on cardiac involvement is unclear. We assessed and compared long-term progression of cardiac involvement according to ERT and non-ERT.METHODS: We retrospectively assessed and compared long-term progression of cardiac involvement in adult patients with FD in the nationwide Danish cohort. We followed clinical signs, symptoms and findings by echocardiography, electrocardiography and Holter-monitoring.RESULTS: We included 66 patients; 47 patients (27 women) received ERT (ERT group) and 19 patients (15 women) did not (non-ERT group). The groups were followed for a median of 8 [0-12] years and 6 [0-13] years, respectively. Comparison between ERT and non-ERT receiving patients by left ventricular mass (echocardiographic assessment) and Sokolow-Lyon voltage- and Cornell product criteria (electrocardiographic assessment) revealed no significant differences. In the ERT group, we observed no change in left ventricular mass but a decrease in Sokolow-Lyon voltage- and Cornell product criteria from baseline to follow-up; 30 mm [15-53] vs. 25 mm [3-44], p < 0.005 and 1710 mm·ms [480-3740] vs. 1520 mm·ms [550-5740], p < .05, respectively. There were no changes within the non-ERT group. During follow-up, cardiac symptoms and use of cardiovascular procedures and -medication increased significantly in the ERT group, whereas no differences were observed within the non-ERT group.DISCUSSION: We raise concerns regarding the efficacy and benefit of ERT on cardiac involvement in Fabry disease and stress the need for further research.

KW - Adolescent

KW - Adult

KW - Aged

KW - Arrhythmias, Cardiac

KW - Denmark

KW - Disease Progression

KW - Echocardiography

KW - Electrocardiography, Ambulatory

KW - Enzyme Replacement Therapy

KW - Fabry Disease

KW - Female

KW - Humans

KW - Hypertrophy, Left Ventricular

KW - Isoenzymes

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Retrospective Studies

KW - Time Factors

KW - Treatment Outcome

KW - Young Adult

KW - alpha-Galactosidase

KW - Comparative Study

KW - Journal Article

U2 - 10.1080/14017431.2017.1332383

DO - 10.1080/14017431.2017.1332383

M3 - Journal article

C2 - 28545342

VL - 51

SP - 207

EP - 216

JO - Scandinavian Cardiovascular Journal

JF - Scandinavian Cardiovascular Journal

SN - 1401-7458

IS - 4

ER -