Fabry's disease (FD) is an X‐linked lysosomal storage disorder caused by the deficient activity of the lysosomal enzyme α‐galactosidase A (α‐Gal A) leading to intracellular accumulation of globotriaosylceramide (Gb3). Patients with amenable mutations can be treated with migalastat, a recently approved oral pharmacologic chaperone to increase endogenous α‐Gal A activity. We assessed safety along with cardiovascular, renal, and patient‐reported outcomes and disease biomarkers in a prospective observational multicenter study after 12 months of migalastat treatment under “real‐world” conditions. Fifty‐nine (28 females) patients (34 (57.6%) pretreated with enzyme replacement therapy) with amenable mutations were recruited. Migalastat was generally safe and well tolerated. Females and males presented with a reduction of left ventricular mass index (primary end point) (−7.2 and −13.7 g/m2, P = 0.0050 and P = 0.0061). FD‐specific manifestations and symptoms remained stable (all P > 0.05). Both sexes presented with a reduction of estimated glomerular filtration rate (secondary end point) (−6.9 and −5.0 mL/minute/1.73 m2; P = 0.0020 and P = 0.0004, respectively), which was most prominent in patients with low blood pressure (P = 0.0271). α‐Gal A activity increased in male patients by 15% from 29% to 44% of the normal wild‐type activity (P = 0.0106) and plasma lyso‐Gb3 levels were stable in females and males (P = 0.3490 and P = 0.2009). Reevaluation of mutations with poor biochemical response revealed no marked activity increase in a zero activity background. We conclude that therapy with migalastat was generally safe and resulted in an amelioration of left ventricular mass. In terms of impaired renal function, blood pressure control seems to be an unattended important goal.

Aims Fabry disease (FD) is an X-linked lysosomal storage disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A (GLA/AGAL) resulting in lysosomal accumulation of globotriaosylceramide (Gb3). Patients with amenable GLA mutations can be treated with migalastat, an oral pharmacologic chaperone increasing endogenous AGAL activity. In this prospective observational multicenter study safety as well as cardiovascular, renal, and patient-reported outcomes and disease biomarkers were assessed after 12 and 24 months of migalastat treatment under “real world” conditions. Methods and results 54 patients (26 females) (33 of these [61.1%] pre-treated with enzyme replacement therapy) with amenable mutations were analyzed. Treatment was generally safe and well tolerated. 153 events per 1,000 patient-years were detected. Overall left ventricular mass index decreased after 24 months (all: -7.5 ± 17.4 g/m2, p = 0.0118; females: -4.6 ± 9.1 g/m2, p = 0.0554; males: -9.9 ± 22.2 g/m2, p = 0.0699). After 24 months, females and males presented with a moderate yearly loss of eGFR (-2.6 and -4.4 ml/min/1.73 m2 per year; p = 0.0317 and p = 0.0028, respectively). FD-specific manifestations/symptoms remained stable (all p > 0.05). 76.9% of females and 50% of males suffered from pain, which has not improved under treatment. FD-specific disease scores (DS3 and MSSI) remained stable during treatment. AGAL activities and plasma lyso-Gb3 values remained stable, although some male patients presented with increasing lyso-Gb3 levels over time. Conclusions Treatment with migalastat was generally safe and resulted in most patients in an amelioration of left ventricular mass. However, due to the heterogeneity of FD phenotypes, it is advisable that the treating physician monitors the clinical response regularly.

Sudden cardiac death (SCD), most often induced by ventricular arrhythmias, is one of the main reasons for cardiovascular-related mortality. While coronary artery disease remains the leading cause of SCD, other pathologies like cardiomyopathies and, especially in the younger population, genetic disorders, are linked to arrhythmia-related mortality. Despite many efforts to enhance the efficiency of risk-stratification strategies, effective tools for risk assessment are still missing. Biomarkers have a major impact on clinical practice in various cardiac pathologies. While classic biomarkers like brain natriuretic peptide (BNP) and troponins are integrated into daily clinical practice, inflammatory biomarkers may also be helpful for risk assessment. Indeed, several trials investigated their application for the prediction of arrhythmic events indicating promising results. Furthermore, in recent years, active research efforts have brought forward an increasingly large number of “novel and alternative” candidate markers of various pathophysiological origins. Investigations of these promising biological compounds have revealed encouraging results when evaluating the prediction of arrhythmic events. To elucidate this issue, we review current literature dealing with this topic. We highlight the potential of “classic” but also “novel” biomarkers as promising tools for arrhythmia prediction, which in the future might be integrated into clinical practice.

Here, we report what we believe to be the first case of bacteraemia with small colony variants of Bacillus licheniformis related to a pacemaker lead infection by B. licheniformis displaying the normal phenotype. Arbitrarily primed PCR analysis showed a clonal strain. The infection was cured after the removal of the infected device. Case reportA 42-year-old immunocompetent man was admitted to the Department of Cardiology of the University Hospital Münster for the treatment of pacemaker lead (PL) infection. Fourteen years previously, the patient had undergone mitral valve replacement with an artificial mechanical valve (TEKNA, size 27 mm) after the removal of a papillary fibroelastoma. Due to a post-operative third degree atrioventricular block, a dual-chamber pacemaker (MDT Kappa 401 DR, Medtronic) had been implanted on the right side of the chest. Eight years later, at the age of 36, a left-sided reimplantation of a dual-chamber pacemaker (Biotronik Axios DR, Biotronik) with right atrial (Medtronic CapSureFix 5076, Medtronic) and right ventricular PLs (Biotronik Merox 60-15 BP) became necessary because of PL dysfunction. The old right-sided pacemaker and PL were removed. Three years following reimplantation (i.e. 3 years prior to the present hospitalization), the patient was admitted with sepsis, and Bacillus licheniformis was identified in five blood cultures. This was preceded by recurrent pneumonia over 6 months and a 12 kg weight loss. A transoesophageal echocardiogram (TOE) showed no evidence of cardiac infection at that time, and positron emission tomography/computed tomography revealed multiple pulmonary densities.Following antibiotic therapy with amoxicillin/clavulanic acid and gentamicin, laboratory parameters normalized and the patient clinically recovered. Three months prior to the present admission, a partial right-lung lobectomy was performed in another hospital after the radiological detection of lung lesions, and the histopathology showed multiple segmental pulmonary embolism. At that time, several TOEs remained non-diagnostic with regard to infective endocarditis (IE).Upon the present admission, the patient reported decreased functional capacity during the last 3 years. He suffered from frequent night sweats, orthostatic dizziness and recurrent pulmonary infections. The patient had a reduced general condition. Upon admission, his C-reactive protein level was 52 mg l 21 and the level of leukocytes was 6840 ml 21 . A TOE revealed a vegetation near the right ventricular PL. Before the initiation of antimicrobial treatment, peripheral blood cultures were collected and three sets grew B. licheniformis. Vancomycin and ceftriaxone therapy was initiated. After identification and antimicrobial susceptibility testing, antibiotic therapy was changed to intravenous amoxicillin/clavulanic acid. The pacemaker and the PLs were removed, and B. licheniformis was also isolated from both atrial and ventricular PLs. At the same time, a new pacemaker (Medtronic Relia SR RESR01) was placed in an abdominal position usi...

BackgroundPatients with Fabry disease (FD) on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in chronic kidney disease epidemiology collaboration-based estimated glomerular filtration rate (eGFR) and a worsened plasma lyso-Gb3 decrease. Hence, the most effective dose is still a matter of debate.MethodsIn this prospective observational study, we assessed end-organ damage and clinical symptoms in 78 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, which were assigned to continue this treatment (agalsidase-beta, regular-dose group, n=17); received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.2 mg/kg) or a direct switch to 0.2 mg/kg agalsidase-alfa (switch group, n=22); or were re-switched to agalsidase-beta after receiving agalsidase-alfa for 12 months (re-switch group, n=39) with a follow-up of 88±25 months.ResultsNo differences for clinical events were observed for all groups. Patients within the re-switch group started with the worst eGFR values at baseline (p=0.0217). Overall, eGFR values remained stable in the regular-dose group (p=0.1052) and decreased significantly in the re-switch and switch groups (p<0.0001 and p=0.0052, respectively). However, in all groups males presented with an annual loss of eGFR by –2.9, –2.5 and −3.9 mL/min/1.73 m² (regular-dose, re-switch, switch groups, all p<0.05). In females, eGFR decreased significantly only in the re-switch group by −2.9 mL/min/1.73 m² per year (p<0.01). Lyso-Gb3 decreased in the re-switch group after a change back to agalsidase-beta (p<0.05).ConclusionsOur data suggest that a re-switch to high dosage of agalsidase results in a better biochemical response, but not in a significant renal amelioration especially in classical males.