Impact of cardio-renal syndrome on adverse outcomes in patients with Fabry disease in a long-term follow-up

• Published in: International journal of cardiology Vol. 249; pp. 261 - 267
• Main Authors: Siegenthaler, M., Huynh-Do, U., Krayenbuehl, P., Pollock, E., Widmer, U., Debaix, H., Olinger, E., Frank, M., Namdar, M., Ruschitzka, F., Nowak, A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15-12-2017
• Subjects: Adult; Aged; Cardio-renal syndrome; Cardio-Renal Syndrome - diagnosis; Cardio-Renal Syndrome - mortality; Cardiovascular Diseases - diagnosis; Cardiovascular Diseases - mortality; Cohort Studies; Fabry disease; Fabry Disease - diagnosis; Fabry Disease - mortality; Female; Follow-Up Studies; Humans; Male; Middle Aged; Mortality - trends; Prospective Studies; Retrospective Studies; Risk factors; Switzerland - epidemiology; Time Factors; Treatment Outcome; Fabry disease; Cardio-renal syndrome; Risk factors
• ISSN: 0167-5273; 1874-1754
• DOI: 10.1016/j.ijcard.2017.09.027

Fabry disease (FD) is a rare X-linked lysosomal storage disease with a deficiency of α-galactosidase A leading to progressive sphingolipid accumulation in different organs, among them heart and kidney. We evaluated the impact of cardio-renal syndrome (CRS) on the incidence of major cardiovascular complications and death in a prospective FD cohort.
A total of 104 genetically proven FD patients were annually followed at the University Hospitals Zurich and Bern. The main outcome was a composite of incident renal replacement therapy (RRT), hospitalisation due to decompensated Heart Failure, new onset atrial fibrillation, pacemaker/ICD implantation, stroke/TIA and death. Estimated glomerular filtration rate (eGFR) and left ventricular myocardial mass index (LVMMI) where explored as the primary exposure variables. During the median follow-up of 103 [59–155] months, events occurred in 27 patients. In a Cox regression analysis, both higher LVMMI and lower eGFR were independently associated with a greater risk of developing adverse events after adjustment for multiple confounders (HR 1.67 [1.04–2.73] P=0.03 per SD increase in LVMMI, HR 0.45 [0.25–0.83], P=0.01 per SD decrease in eGFR). In patients with CRS, the risk to develop events was significantly increased if adjusted for demographics and RRT (HR 4.46 [1.07–18.62], P=0.04), approaching significance if additionally adjusted for hypertension (HR 4.05 [0.95–17.29], P=0.06). In Kaplan-Meier-Analysis, the poorest event-free survival was observed among patients with CRS.
CRS was associated with a high risk to develop cardiovascular complications and death, emphasizing the importance of its prevention and early recognition. A focus on cardio-reno-protective therapies is crucial.