Cardiomyopathy and cardiovascular events by gender in a comprehensive Finnish patient population with Fabry disease

Abstract

Abstract Background/Introduction Fabry disease (FD) is a lysosomal storage disorder caused by mutations in the α- galactosidase A gene (GLA) leading to lack of an active GLA enzyme and accumulation of glycosphingolipids in different organs, including heart. Because of X-linked inheritance, the phenotype is usually more severe in males than in females. Purpose There are very few national studies on FD. Our aim was to investigate the genetics, phenotype, treatment and prognosis of Finnish Fabry patients by gender. Methods Finnish Fabry Registry includes 98 patients, approximately 90% of all Finnish patients with FD, diagnosed from 1972 to 2018. Cardiovascular, neurological and renal events, and cardiac imaging data were recorded from medical charts until 2020. Cardiac ultrasound and MRI (CMR) were performed in 86% and 77% of females and 88% and 78% of males, respectively. Results Altogether, 24 different pathogenic GLA mutations were found in 66 females and 32 males from 27 Finnish families. FD, or the causative mutation, was diagnosed at an average age of 41 years in females, and at 29 years in males. During the mean 17 years of follow-up, either ERT or migalastat was started for 58% of females and 88% of males. At the end of the follow-up, Fabry cardiomyopathy (FCM; maximal left ventricular wall thickness (LVMWT) 13 mm or more in cardiac imagining) had been diagnosed in 47% of females and 66% of males at the mean age of 55 years and 41 years, respectively. Atrial fibrillation (AF) was diagnosed in 21% of females and 9% of males. Heart failure (HF) due to FCM was diagnosed in 20% of females and in 12% of males at the mean age of 62 and 54 years, respectively. A bradycardia pacemaker was required for 9 females and for 2 males and one female and one male had also implantable cardioverter defibrillator. Over 20% of both female and male FD patients suffered a stroke during the follow-up. End-stage kidney disease was not found in females, but 9% of males received a renal transplantation. During the follow-up 5 females and 3 males died. The mean age at death was 77 years in females, and 48 years in males. All deceased males and 40% of females had been treated with ERT from an average age of 40 and 66 years, respectively. All deceased subjects had FCM. All females and one male died of FD. Two females died of a stroke and three of HF. All deceased males had severe classical FD phenotype. One male suffering from severe HF died of a stroke. One male with an ICD and renal transplant, died of malignancy. The third male withdrew from follow-up and died of gastrointestinal bleeding. Conclusions In Finnish patients with FD, cardiomyopathy, related arrhythmias and heart failure were common in both genders. All eight deceased subjects had Fabry cardiomyopathy, and the immediate cause of death was most often heart failure or stroke. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Heart Research Foundationand Sanofi Genzyme