A review and recommendations for oral chaperone therapy in adult patients with Fabry disease.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder affecting both males and females caused by genetic abnormalities in the gene encoding the enzyme α-galactosidase A. FD-affected patients represent a highly variable clinical course with first symptoms already appearing in young age. The disease causes a progressive multiple organ dysfunction affecting mostly the heart, kidneys and nervous system, eventually leading to premature death. Disease-specific management of FD includes enzyme replacement therapy with agalsidase α and ß or pharmacological oral chaperone migalastat. Migalastat is a low-molecular-mass iminosugar, that reversibly binds to active site of amenable enzyme variants, stabilizing their molecular structure and improving trafficking to the lysosome. Migalastat was approved in the EU in 2016 and is an effective therapy in the estimated 35-50% of all patients with FD with amenable GLA gene variants. This position statement is the first comprehensive review in Central and Eastern Europe of the current role of migalastat in the treatment of FD. The statement provides an overview of the pharmacology of migalastat and summarizes the current evidence from the clinical trial program regarding the safety and efficacy of the drug and its effects on organs typically involved in FD. The position paper also includes a practical guide for clinicians on the optimal selection of patients with FD who will benefit from migalastat treatment, recommendations on the optimal selection of diagnostic tests and the use of tools to identify patients with amenable GLA mutations. Areas for future migalastat clinical research have also been identified.

Pol-CDRIE registry - 1-year observational data on patients hospitalized due to cardiac device-related infective endocarditis in Polish referential cardiology centres.

BACKGROUND: The rate of cardiac device-related infective endocarditis (CDRIE) is increasing worldwide, but no detailed data are available for Poland. AIMS: We aimed to evaluate clinical, diagnostic, and therapeutic data of patients hospitalized due to CDRIE in 22 Polish referential cardiology centers from May 1, 2016 to May 1, 2017. METHODS: Participating cardiology departments were asked to fill in a questionnaire that included data on the number of hospitalized patients, number and types of implanted cardiac electrotherapy devices, and number of infective endocarditis cases. We also collected clinical data and data regarding the management of patients with CDRIE. RESULTS: Overall, 99 621 hospitalizations were reported. Infective endocarditis unrelated to cardiac device was the cause of 596 admissions (0.6%), and CDRIE, of 195 (0.2%). Pacemaker was implanted in 91 patients with CDRIE (47%); cardioverter­defibrillator, in 51 (26%); cardiac resynchronization therapy­defibrillator, in 48 (25%); and cardiac resynchronization therapy­pacemaker, in 5 (2.5%). The most common symptoms were malaise (62%), fever/chills (61%), cough (21%), chest pain (19.5%), and inflammation of the device pocket (5.6%). Cultures were positive in 77.5% of patients. The cardiac device was removed in 91% of patients. The percutaneous approach was most common for cardiac device removal. All patients received antibiotic therapy, and 3 patients underwent a heart valve procedure. Transesophageal echocardiography was performed in 80% of patients. The most common complication was heart failure (25% of patients). CONCLUSIONS: The clinical profile, pathogen types, and management strategies in Polish patients with CDRIE are consistent with similar data from other European countries. Transesophageal echocardiography was performed less frequently than recommended. The removal rate in the Polish population is consistent with the general rates observed for interventional treatment in patients with CDRIE.

Omega-3 fatty acids supplementation improves endothelial function and maximal oxygen uptake in endurance-trained athletes.

The study aimed to evaluate the effects of a 3-week n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation on serum nitric oxide (NO), asymmetric dimethyloarginine (ADMA), ultrasound indices of endothelial function and maximal oxygen uptake (VO2 max) of elite cyclists. The effects of dietary supplementation (n-3 PUFA at a dose of 1.3 g twice daily for 3 weeks) and placebo administration on flow-mediated dilatation (FMD), pulse wave velocity, serum markers (NO, ADMA), lipid profile, and ΔVO2max were analysed in 13 cyclists both before and after dietary protocols. Significant differences between pre- and post-intervention baseline NO levels were observed after n-3 PUFA dietary protocol (13.9 ± 4.2 vs. 23.5 ± 3.6 µmol·l(-1); P < 0.001). Higher post-intervention baseline NO level was observed after n-3 PUFA diet compared with placebo (23.5 ± 3.6 vs. 15.3 ± 3.0 µmol·l(-1); P < 0.01, respectively). The n-3 PUFA increased baseline NO concentration (ΔNO) by 6.7 ± 3.8 µmol·l(-1) and placebo by 1.6 ± 4.4 µmol·l(-1). The positive correlation was observed between baseline post-intervention NO concentration and maximal oxygen uptake (r = 0.72; P < 0.01) and also between ΔNO and ΔVO2max (r = 0.54; P < 0.05) in response to omega-3 fatty acids supplementation. There was an association between a 5.25% higher FMD (P < 0.05) and higherΔVO2max (P < 0.001) after n-3 PUFA diet compared with lower values of placebo (r = 0.68; P < 0.05). These findings suggest that an increase in NO release in response to n-3 PUFA supplementation may play a central role in cardiovascular adaptive mechanisms and enhanced exercise performance in cyclists.

The use of iloprost in the treatment of 'out of proportion' pulmonary hypertension in chronic obstructive pulmonary disease.

CASE: Pulmonary hypertension secondary to respiratory disease most often occurs as a complication of chronic obstructive pulmonary disease, which currently constitutes one of the leading causes of death. Some patients with hypoxaemia reveal "out of proportion" pulmonary hypertension with inappropriate increase of pulmonary artery pressure. Iloprost, analogue of prostacyclin, dilates systemic vessels and pulmonary vessels in particular if administered by inhalation. It appears to be important, life-saving, complementary therapy. However, there is no evidence for its routine use in out of proportion arterial pulmonary hypertension. This case study presents a 44-year old man with chronic obstructive pulmonary disease and "out of proportion" pulmonary hypertension. We present the results of his treatment with iloprost. CONCLUSION: In a patient with "out of proportion" pulmonary hypertension due to chronic obstructive pulmonary disease, inhaled iloprost led to improvement in clinical status and echocardiographic parameters, including a reduction of right ventricular systolic pressure.

Effects of n-3 polyunsaturated fatty acids on depressive symptoms, anxiety and emotional state in patients with acute myocardial infarction.

BACKGROUND: Our aim was to assess whether an early introduced n-3 polyunsaturated fatty acids (n-3 PUFA) supplementation affects depression symptoms, anxiety and emotional state in patients with acute myocardial infarction (AMI) and no history of mental disorders. METHODS: Fifty two patients with AMI were enrolled into the study and randomized to the study group (group P; n=26; standard therapy+n-3 PUFA 1 g daily) or the control group (group C; n=26; standard therapy). The following psychological tests were used at the baseline (3rd day of AMI) and after one month (30±1 days): Beck Depression Inventory (BDI), State-Trait Anxiety Inventory in a specific situation (STAI-S) and as a general trait (STAI-T), Emotional State Questionnaire (ESQ). RESULTS: The baseline characteristics, pharmacotherapy and BDI, STAI-S/T and ESQ were similar between both groups. The mean test scores assessed for all patients (group P and C) during the one-month observation were significantly lower for BDI (p=0.04), STAI-T (p=0.03), STAI-S (p=0.01) and harm/loss emotions (p=0.005). After adjusting for age, sex, body mass index, coronary artery disease severity, ejection fraction, serum troponin level and the baseline tests results, n-3 PUFA intervention revealed additional significant decrease in BDI (p=0.046), STAI-S (p=0.03) and harm/loss emotions (p=0.04). CONCLUSIONS: Our study provides novel and preliminary observations--n-3 PUFA supplementation reveals additional decreasing effects on depressive and anxiety symptoms in early post-MI patients.

N-3 polyunsaturated fatty acids do not influence the efficacy of dual antiplatelet therapy in stable angina pectoris patients after percutaneous coronary intervention.

BACKGROUND: We aimed to prospectively assess the influence of the recommended dose, 1.0 g of polyunsaturated fatty acids (N-3 PUFA) daily, on platelet reactivity in patients with stable angina pectoris (SAP) after elective percutaneous coronary intervention (PCI). METHODS: Forty consecutive patients with SAP and successful PCI were randomized to the study group (group PUFA: n = 20; age 65 ± 8; standard therapy + 75 mg acetylsalicylic acid + 75 mgclopidogrel + N-3 PUFA/Omacor 1 g daily) and the control group (group C: n = 20; age 65 ± 9; standard therapy + 75 mg acetylsalicylic acid + 75 mg clopidogrel). Platelet reactivity tests (COL, TRAP, ASPI, ADP) were performed using whole blood aggregometry (multiplate platelet [PLT] function analysis) on the 2,nd and 30th day after PCI. RESULTS: Baseline patients' characteristics and clinical outcomes were comparable between the groups. There were no differences between both groups in the mean values of the PTL tests measured 30 days after PCI (PUFA vs. C ASPI: 18.5 ± 17 vs. 27 ± 29 U, COL: 30.4 ± 14.3 vs. 30.3 ± 13.4 U, ADP: 25.4 ± 16.1 vs. 20 ± 10.7 U, TRAP: 65.8 ± 25.6 vs. 57.1 ± 20.4 U, p = NS). The mean delta values of the PTL tests (18-24 h post-PCI/30 days post-PCI) were also comparable between the groups. The PTL aggregometry results were related to time - the baseline values of the ADP (p = 0.003), COL (p = 0.037) and TRAP (p < 0.001) tests were smaller and the ASPI (p = 0.027) test was higher than those measured after 1-month. CONCLUSIONS: N-3 PUFA supplementation does not affect the efficacy of dual antiplatelettherapy in patients with SAP after PCI.

N-3 polyunsaturated fatty acids early supplementation improves ultrasound indices of endothelial function, but not through NO inhibitors in patients with acute myocardial infarction: N-3 PUFA supplementation in acute myocardial infarction.

BACKGROUND & AIMS: Our aim was to evaluate early initiated one month n-3 polyunsaturated fatty acids (PUFA) supplementation effects on ultrasound indices of endothelial function and serum asymmetric dimethylarginine (ADMA) levels in patients with acute myocardial infarction (AMI). METHODS: Forty patients with AMI and successful percutaneous coronary intervention (PCI) were recruited into the study and randomized to the study group (group P; n = 20; standard therapy + n-3 PUFA 1 g daily) or the control group (group C; n = 20; standard therapy). Ultrasound indices of endothelial function: flow-mediated dilatation (FMD), nitroglycerin-mediated dilatation (NMD) and serum ADMA concentrations (ELISA) were obtained before and after one month (30 ± 1 days) therapy (presented as means ± standard deviations). RESULTS: There was a significant difference between both groups in mean delta (baseline/after one month) FMD (P: 8.1 ± 12.6% vs C: -2.2 ± 11.8%; p = 0.02) with no difference in mean delta NMD (P: 3.3 ± 11.9% vs 0.66 ± 14.3%; p = 0.53). We found also a significant increase in mean FMD (7.4 ± 6.4 to 15.5 ± 10.5%; p = 0.02) with a nonsignificant change in mean NMD values (26.9 ± 12.1 to 30.2 ± 14.0%; p = 0.24) after 1-month therapy with n-3 PUFA. FMD and NMD mean values did not change in control patients (FMD: 11.6 ± 6.1% to 9.4 ± 8.0%; p = 0.5 NMD: 25.1 ± 11.4% to 25.8 ± 14.0%; p = 0.84). The comparison of mean delta ADMA values for both groups revealed no differences (P: 6.2 ± 9.7 µmol/l vs C: 3.6 ± 9.5 µmol/l; p = 0.43). Mean serum ADMA concentrations were significantly increased after 1-month therapy in the group P (P: 2.1 ± 1.8 to 8.3 ± 9.7 µmol/l; p = 0.001; C: 4.5 ± 7.1 to 8.1 ± 9.5 µmol/l; p = 0.09). However, there was a nonsignificant difference in mean baseline serum ADMA levels between both groups (P: 2.1 ± 1.8 µmol/l vs C: 4.5 ± 7.1 µmol/l; p = 0.32). There were no significant correlations between FMD, NMD, ADMA levels and demographic, clinical or biochemical parameters. CONCLUSIONS: Early and short-term n-3 PUFA supplementation improved ultrasound indices of endothelial function without affecting serum ADMA levels in patients with AMI and successful primary PCI.

Influence of calcium and vitamin D supplementation on weight and fat loss in obese women.

BACKGROUND: Dairy products not only reduce the risk of hypertension and cardiovascular diseases but may play a role in the treatment of obesity. As there is some evidence that calcium (Ca) and vitamin D may play a role in effective weight management, we decided to evaluate the influence of Ca and vitamin D supplementation on weight and fat loss in obese women. MATERIAL AND METHODS: Forty obese women were enrolled in this study. Subjects were divided into 2 groups comparable with body mass index (BMI) and age. Group 1 was provided with calcium carbonate and 1-(OH)-vitamin D supplementation. Group 2 was provided with only a diet. Subjects participated in a 3-month weight reduction therapy (balanced diet, modification of life style, and regular physical exercise). Blood samples (serum concentration of Ca, phosphorus (P), parathormone (PTH), 25-(OH)-D3) and clinical characteristics (weight, height, BMI, body composition) were taken at baseline and after the 3-month program. RESULTS: No significant differences of body weight, body fat content, serum parathormone, 25-(OH)-D3 concentration, and plasma total Ca and P concentration were observed between analyzed groups both before and after the treatment. Additionally, we did not observe any significant influence of Ca and vitamin D supplementation on weight and fat loss. CONCLUSION: Ca plus vitamin D supplementation during a 3-month low caloric diet has no additional effect on weight and fat loss in obese women.