Fabry disease (FD) is an X‐linked lysosomal storage disorder caused by pathogenic variants in the α‐galactosidase A gene (GLA ) that leads to reduced or undetectable α‐galactosidase A (AGAL‐A) enzyme activity and progressive accumulation of globotriaosylceramide (Gb₃) and its deacylated form globotriaosylsphingosine (lysoGb₃) in cells throughout the body. FD can be multisystemic with neurological, renal, cutaneous and cardiac involvement or be limited to the heart. Cardiac involvement is characterized by progressive cardiac hypertrophy, fibrosis, arrhythmias, heart failure and sudden cardiac death. The cardiac management of FD requires specific measures including enzyme replacement therapy or small pharmacological chaperones in patients carrying amenable pathogenic GLA gene variants and more general management of cardiac symptoms and complications. In this paper, we summarize current knowledge of FD related heart disease and expert consensus recommendations for its management.

BackgroundThe novel cryoballoon Advance (CB-A) has proven to achieve significantly lower temperatures and faster pulmonary vein isolation (PVI) times in comparison with the first-generation device. Although acutely very effective, to the best of our knowledge, data on mid-term clinical follow-up is lacking.AimsThe aim of the study was to analyse the freedom from recurrence of atrial fibrillation (AF) on a 1-year follow-up period, in a series of consecutive patients having undergone PVI with the CB-A for paroxysmal AF (PAF).Methods and resultsForty-two patients [30 male (71%); mean age: 57.9 ± 21.1 years] were included. All patients underwent a procedure with the large 28 mm CB-A. A total 168 PVs were depicted on the pre-procedural computed tomography scan. All PVs (100%) could be isolated with the CB only. The freedom from AF off-antiarrhythmic drug treatment after a single procedure was 78% of patients at a mean 11.6 ± 2.0 months follow-up. If considering a blanking period (BP) of 3 months, success rate was 83%. Phrenic nerve palsy (PNP) was the most frequent complication occurring in 19% of individuals.ConclusionThe CB-A is very effective in producing PVI and affords freedom from AF at 12 months follow-up in 83% of patients affected by drug-resistant PAF following a 3-month BP. The most frequent complication observed was PNP which occurred in 19% of patients. All PNP reverted during follow-up.

Enzyme replacement therapy (ERT) with recombinant human α-galactosidase has been available for the treatment of Fabry disease since 2001 in Europe and 2003 in the USA. Treatment outcomes with ERT are dependent on baseline patient characteristics, and published data are derived from heterogeneous study populations. We conducted a comprehensive systematic literature review of all original articles on ERT in the treatment of Fabry disease published up until January 2017. This article presents the findings in adult male patients. Clinical evidence for the efficacy of ERT in adult male patients was available from 166 publications including 36 clinical trial publications. ERT significantly decreases globotriaosylceramide levels in plasma, urine, and in different kidney, heart, and skin cell types, slows the decline in estimated glomerular filtration rate, and reduces/stabilizes left ventricular mass and cardiac wall thickness. ERT also improves nervous system, gastrointestinal, pain, and quality of life outcomes. ERT is a disease-specific treatment for patients with Fabry disease that may provide clinical benefits on several outcomes and organ systems. Better outcomes may be observed when treatment is started at an early age prior to the development of organ damage such as chronic kidney disease or cardiac fibrosis. Consolidated evidence suggests a dose effect. Data described in male patients, together with female and paediatric data, informs clinical practice and therapeutic goals for individualized treatment.