Pegunigalsidase alfa, a PEGylated α-galactosidase A enzyme replacement therapy (ERT) for Fabry disease, has a longer plasma half-life than other ERTs administered intravenously every 2 weeks (E2W). BRIGHT (NCT03180840) was a phase III, open-label study in adults with Fabry disease, previously treated with agalsidase alfa or beta E2W for ≥3 years, who switched to 2 mg/kg pegunigalsidase alfa every 4 weeks (E4W) for 52 weeks. Primary objective assessed safety, including number of treatment-emergent adverse events (TEAEs). Thirty patients were enrolled (24 males); 23 previously received agalsidase beta. Pegunigalsidase alfa plasma concentrations remained above the lower limit of quantification throughout the 4-week dosing interval. Thirty-three of 182 TEAEs (in 9 patients) were considered treatment-related; all were mild/moderate. No patients developed de novo anti-drug antibodies (ADAs). In the efficacy analysis (n = 29), median (inter-quartile range) eGFR change from baseline over 52 weeks was -1.9 (-5.9; 1.8) mL/min/1.73 m2 (n = 28; males [n = 22]: -2.4 [-5.2; 3.2]; females [n = 6]: -0.7 [-9.2; 2.0]). Overall, median eGFR slope was -1.9 (-8.3; 1.9) mL/min/1.73 m2/year (ADA-negative [n = 20]: -1.2 [-6.4; 2.6]; ADA-positive [n = 9]: -8.4 [-11.6; -1.0]). Lyso-Gb3 concentrations were low and stable in females, with a slight increase in males (9/24 ADA-positive). The BRIGHT study results suggest that 2 mg/kg pegunigalsidase alfa E4W is tolerated well in stable adult patients with Fabry disease. Due to the low number of patients in this study, more research is needed to demonstrate the effects of pegunigalsidase alfa given E4W. Further evidence, outside of this clinical trial, should be factored in for physicians to prolong the biweekly ERT intervals to E4W. TAKE-HOME MESSAGE: Treatment with 2 mg/kg pegunigalsidase alfa every 4 weeks could offer a new treatment option for patients with Fabry disease.

• MeSH
• alpha-Galactosidase * administration & dosage   therapeutic use   MeSH
• Adult MeSH
• Enzyme Replacement Therapy * methods   MeSH
• Fabry Disease * drug therapy   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Polyethylene Glycols administration & dosage   MeSH
• Recombinant Proteins * administration & dosage   therapeutic use   MeSH
• Drug Administration Schedule MeSH
• Aged MeSH
• Sphingolipids blood   MeSH
• Trihexosylceramides blood   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial, Phase III MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH

AIMS: Among patients with cardiogenic shock, immediate initiation of extracorporeal membrane oxygenation (ECMO) did not demonstrate any benefit at 30 days. The present study evaluated 1-year clinical outcomes of the Extracorporeal Membrane Oxygenation in the therapy of Cardiogenic Shock (ECMO-CS) trial. METHODS AND RESULTS: The ECMO-CS trial randomized 117 patients with severe or rapidly progressing cardiogenic shock to immediate initiation of ECMO or early conservative strategy. The primary endpoint for this analysis was 1-year all-cause mortality. Secondary endpoints included a composite of death, resuscitated cardiac arrest or implantation of another mechanical circulatory support device, duration of mechanical ventilation, and the length of intensive care unit (ICU) and hospital stays. In addition, an unplanned post-hoc subgroup analysis was performed. At 1 year, all-cause death occurred in 40 of 58 (69.0%) patients in the ECMO arm and in 40 of 59 (67.8%) in the early conservative arm (hazard ratio [HR] 1.02, 95% confidence interval [CI] 0.66-1.58; p = 0.93). The composite endpoint occurred in 43 (74.1%) patients in the ECMO group and in 47 (79.7%) patients in the early conservative group (HR 0.83, 95% CI 0.55-1.25; p = 0.29). The durations of mechanical ventilation, ICU stay and hospital stay were comparable between groups. Significant interaction with treatment strategy and 1-year mortality was observed in subgroups according to baseline mean arterial pressure (MAP) indicating lower mortality in the subgroup with low baseline MAP (<63 mmHg: HR 0.58, 95% CI 0.29-1.16; pinteraction = 0.017). CONCLUSIONS: Among patients with severe or rapidly progressing cardiogenic shock, immediate initiation of ECMO did not improve clinical outcomes at 1 year compared to the early conservative strategy. However, immediate ECMO initiation might be beneficial in patients with advanced haemodynamic compromise.

• MeSH
• Time Factors MeSH
• Intensive Care Units MeSH
• Shock, Cardiogenic * therapy   mortality   MeSH
• Middle Aged MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation * methods   MeSH
• Survival Rate trends   MeSH
• Aged MeSH
• Respiration, Artificial methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

Fabry disease is a progressive, X-linked lysosomal disorder caused by reduced or absent α-galactosidase A activity due to GLA variants. The effects of migalastat were examined in a cohort of 125 Fabry patients with migalastat-amenable GLA variants in the followME Pathfinders registry (EUPAS20599), an ongoing, prospective, patient-focused registry evaluating outcomes for current Fabry disease treatments. We report annualised estimated glomerular filtration rate (eGFR) and Fabry-associated clinical events (FACEs) in a cohort of patients who had received ≥3 years of migalastat treatment in a real-world setting. As of August 2022, 125 patients (60% male) had a mean migalastat exposure of 3.9 years. At enrolment, median age was 58 years (males, 57; females, 60) with a mean eGFR of 83.7 mL/min/1.73 m2 (n = 122; males, 83.7; females, 83.8) and a median left ventricular mass index of 115.1 g/m2 (n = 61; males, 131.2; females, 98.0). Mean (95% confidence interval) eGFR annualised rate of change in the overall cohort (n = 116) was -0.9 (-10.8, 9.9) mL/min/1.73 m2/year with a similar rate of change observed across patients with varying levels of kidney function at enrolment. Despite population age and baseline morbidity, 80% of patients did not experience a FACE during the mean 3.9 years of migalastat exposure. The incidence of renal, cardiac, and cerebrovascular events was 2.0, 83.2, and 4.1 events per 1000 patient-years, respectively. These data support a role of migalastat in preserving renal function and multisystem effectiveness during ≥3 years of migalastat treatment in this real-world Fabry population.

• MeSH
• 1-Deoxynojirimycin * analogs & derivatives   therapeutic use   MeSH
• alpha-Galactosidase * therapeutic use   MeSH
• Adult MeSH
• Fabry Disease * drug therapy   MeSH
• Glomerular Filtration Rate * MeSH
• Kidney physiopathology   drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Prospective Studies MeSH
• Registries * MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• Publication type
• Meeting Abstract MeSH

• Publication type
• Newspaper Article MeSH
• Interview MeSH

• Publication type
• Newspaper Article MeSH
• Interview MeSH

Fabry disease is an X-linked lysosomal storage disorder that causes accumulation of glycosphingolipids in body tissues and fluids, leading to progressive organ damage and life-threatening complications. It can affect both males and females and can be classified into classic or later-onset phenotypes. The disease severity in females ranges from asymptomatic to the more severe, classic phenotype. Most females are hemizygous and the X-linked inheritance is associated with variable X-activation pattern and residual enzymatic activity. The heterogeneity of clinical presentation in females requires different approaches to diagnosis and management than males. A European group of 7 physicians, experienced in the management of Fabry disease, convened to discuss patient perspectives and published guidelines. The experts discussed the need to focus on psychological treatment in relation to individual coping styles when monitoring targets, and the lack of data supporting the use of plasma globotriaosylsphingosine over enzyme activity in the diagnosis of these patients. It was suggested that the high phenotypic variability in female patients may be related to the dynamic nature of the X-chromosome inactivation process and further understanding of this process could help predict the progression of Fabry disease in females and facilitate timely intervention. Due to the range of disease severity they exhibit, female patients with Fabry disease may require a more individualized treatment approach than males. Despite current recommendations, the experts agreed that early disease-specific treatment initiation in high-risk females could improve clinical outcome.

• MeSH
• Fabry Disease * therapy   genetics   diagnosis   MeSH
• Humans MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

• Publication type
• Editorial MeSH

• About
• Libenský, Václav, 1877-1938 Authority

Kardiomyopatie představují širokou skupinu onemocnění, která vyžadují specifické diagnostické a léčebné postupy. Na rozdíl od častých onemocnění zahrnuje tato skupina některé vzácnější jednotky, jejichž diagnóza vyžaduje vysoký stupeň expertizy a dostupnost moderních zobrazovacích a laboratorních diagnostických metod. V současné době se mimoto začíná objevovat specifická léčba pro některá tato onemocnění (obstrukční hypertrofická kardiomyopatie, srdeční amyloidóza, Fabryho a Pompeho choroba a další). Tato léčba spadá většinou do kategorie vysoce nákladných léčiv, podléhá řadě indikačních omezení a vyžaduje nadstandardní a převážně vysoce intenzivní monitoraci nemocných. V součtu tak diagnostika a léčba kardiomyopatií vyžaduje centralizaci v expertních centrech s dostatečnou materiální i personální výbavou a jednání s plátci péče tak, aby tato centra měla přístup k vybraným typům léčby pro nemocné, o něž se stará. Tento dokument sestavený Pracovní skupinou pro choroby myokardu a perikardu České kardiologické společnosti představuje konsenzus odborníků specifikující , jak by měla být specializovaná pracoviště pro kardiomyopatie v současné době vybavena. Přepokládá se, že tato centra budou formálně ustavena a budou moci poskytovat celé spektrum péče včetně inovativních a regulovaných léčiv.

Cardiomyopathies encompass a diverse group of diseases requiring specialized diagnostic and therapeutic approaches. Unlike more common conditions, some rarer forms demand advanced expertise and access to modern imaging and diagnostic tools. Recently, targeted treatments for diseases like obstructive hypertrophic cardiomyopathy, cardiac amyloidosis, Fabry, and Pompe disease have emerged. These therapies are often high-cost, subject to strict indications, and necessitate intensive patient monitoring. Given the complexity, diagnosis and treatment should be centralized in expert centers with adequate resources and coor- dination with healthcare payers to ensure an access to these treatments. This document, prepared by the Working Group on Myocardial and Pericardial Diseases of the Czech Society of Cardiology, outlines expert consensus on the necessary infrastructure for specialized cardiomyopathy units, which are expected to offer comprehensive care, including innovative and regulated therapies.

• MeSH
• Cardiac Imaging Techniques classification   MeSH
• Cardiology organization & administration   MeSH
• Cardiomyopathies * diagnostic imaging   drug therapy   therapy   MeSH
• Humans MeSH
• Multimodal Imaging methods   MeSH
• Heart Diseases diagnostic imaging   drug therapy   therapy   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Practice Guideline MeSH

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

• MeSH
• Walking MeSH
• Ventricular Dysfunction, Left * MeSH
• Ventricular Function, Left MeSH
• Quality of Life MeSH
• Humans MeSH
• Aged MeSH
• Heart Failure * therapy   drug therapy   MeSH
• Stroke Volume MeSH
• Life Style MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Randomized Controlled Trial MeSH