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.

Considerations for Home-Based Treatment of Fabry Disease in Poland during the COVID-19 Pandemic and Beyond.

Current therapy for Anderson-Fabry disease in Poland includes hospital or clinic-based intravenous enzyme replacement therapy with recombinant agalsidase alpha or beta, or oral pharmacological chaperone therapy with migalastat. Some countries around the world offer such treatment to patients in the comfort of their own homes. The 2020-2021 COVID-19 pandemic has pushed global healthcare providers to evolve their services so as to minimize the risk of COVID-19 exposure to both patients and providers; this has led to advances in telemedicine services and the increasing availability of at-home treatment for various procedures including parenteral drug administration. A total of 80% of surveyed Anderson-Fabry disease patients in Poland would prefer home-based treatment, which would be a safe and convenient alternative to clinic-based treatment if patient selection is based on our proposed algorithm. Our recommendations for home-based treatments appear feasible for the long term care of Anderson-Fabry disease patients during the COVID-19 pandemic and beyond. This may also serve as a basis for home-based treatment programs in other rare and ultra-rare genetic diseases.

Echocardiography during the coronavirus disease 2019 pandemic - the impact of the vaccination program. A 2021 update of the expert opinion of the Working Group on Echocardiography of the Polish Cardiac Society.

The coronavirus disease 2019 (COVID-19) pandemic resulted in an urgent need to reorganize the work of echocardiography laboratories in order to ensure the safety of patients and the protection of physicians, technicians, and other staff members. In the previous Expert Opinion of the Working Group on Echocardiography of Polish Cardiac Society we provided recommendations for the echocardiographic services, in order to ensure maximum possible safety and efficiency of imagers facing epidemic threat. Now, with much better knowledge and larger experience in treating COVID-19 patients and with introduction of vaccination programs, we present updated recommendations for performing transthoracic and transesophageal examinations, including information on the potential impact of personnel and the patient vaccination program, and growing numbers of convalescents on performance of echocardiographic laboratories, with the goal of their ultimate reopening.

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.

Sudden Cardiac Death in Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a heart disease characterized by hypertrophy of the left ventricular myocardium and is most often caused by mutations in sarcomere genes. The structural and functional abnormalities are not explained by flow-limiting coronary artery disease or loading conditions. The disease affects at least 0.2% of the population worldwide and is the most common cause of sudden cardiac death in young people and competitive athletes because of fatal ventricular arrhythmia. In some patients, however, HCM has a benign course. Therefore, it is of utmost importance to properly evaluate patients and single out those who would benefit from an implanted cardioverter defibrillator. In this article, we review and summarize the sudden cardiac death risk stratification algorithms, methods of preventing death due to HCM, and novel factors that may improve the existing prediction models.

Lactobacillus gasseri endocarditis on the aortic valve bioprosthesis - a case report.

Lactobacillus is a genus of Gram-positive, facultative anaerobic/ microaerophilic, rod-shaped bacteria. Lactobacilli constitute a significant component of the human microbiota in the oral cavity, gastrointestinal tract and female urogenital tract. They are also widely used as probiotics. Rarely, especially in patients with impaired immunity or with structural heart disease, do Lactobacilli become the pathogen responsible for serious infections, e.g. infective endocarditis (IE). CASE REPORT: The authors describe a case of an 80-year-old female with a past history of aortic valve replacement, mitral annuloplasty and pacemaker implantation admitted to hospital due to weakening, subfebrile state and chills. In transesophageal echocardiography vegetations on the aortic valve bioprosthesis were found, while pacemaker electrodes and mitral annulus were not involved in the endocarditis process. Bacteriological work-up revealed growth of L. gasseri. The patient was successfully treated with amoxicillin/clavulanate acid (six weeks) and with gentamycin (two weeks). No recurrence of the disease was observed during a six-month posthospital follow-up. Among different species of Lactobacillus, L. gasseri has not been reported as an IE pathogen so far. Lack of unequivocal data as to whether using probiotics may be responsible for infections, including IE, in patients with predisposing conditions.

Safety, feasibility and effectiveness of first in-human administration of muscle-derived stem/progenitor cells modified with connexin-43 gene for treatment of advanced chronic heart failure.

AIMS: To assess the safety and efficacy of transendocardial delivery of muscle-derived stem/progenitor cells with connexin-43 overexpression (Cx-43-MDS/PC) in advanced heart failure (HF). METHODS AND RESULTS: Thirteen subjects with advanced HF, New York Heart Association (NYHA) class II-III were enrolled and treated with targeted injection of Cx-43-MDS/PCs and then monitored for at least 6 months. Overexpression of Cx43 (Cx43+) was significantly higher in all but one subject (Cx43-). Injection of MDS/PCs was associated with significant improvement of exercise capacity: NYHA (3 ± 0 vs. 1.8 ± 0.7, P = 0.003), exercise duration (388.69 ± 141.83 s vs. 462.08 ± 176.69 s, P = 0.025), peak oxygen consumption (14.38 ± 3.97 vs. 15.83 ± 3.74 ml/kg.min, P = 0.022) and oxygen pulse (10.58 ± 2.89 vs. 18.88 ± 22.63 mLO2 /heart rate, P = 0.012). Levels of BNP, left ventricular (LV) ejection fraction and LV end-diastolic volumes tended to improve. There was a significant improvement of the mean unipolar voltage amplitudes measured for the injected segments and the entire left ventricle (9.62 ± 2.64 vs. 11.62 ± 3.50 mV, P = 0.014 and 8.83 ± 2.80 vs. 10.22 ± 3.41 mV, P = 0.041, respectively). No deaths were documented, Cx43+ (n = 12) subjects presented no significant ventricular arrhythmia; one Cx43- subject suffered from ventricular tachycardia (successfully treated with amiodarone). CONCLUSIONS: Injection of Cx-43-MDS/PCs in patients with severe HF led to significant improvement in exercise capacity and myocardial viability of the injected segments while inducing no significant ventricular arrhythmia. This may arise from improved electrical coupling of the injected cells and injured myocardium and thus better in-situ mechanical cooperation of both cell types. Therefore, further clinical studies with Cx43+ MDS/PCs are warranted.

The new generation is coming. Percutaneous implantation of the fully repositionable Lotus® aortic valve prosthesis: the first Polish experience.

Transcatheter aortic valve implantation (TAVI) is nowadays an accepted method of treatment for patients with symptomatic severe aortic stenosis who are inoperable or at very high risk of classic surgical aortic valve replacement. The Lotus valve system is a new generation TAVI device composed of a self-expanding stent prosthesis with implemented bovine pericardial leaflets, which is designed to facilitate repositioning, resheathing, and retrieval, even in the fully expanded and functioning position before the final release. In addition, the Lotus valve is surrounded by a flexible membrane to seal paravalvular gaps between the prosthesis and native valve. We present the first Polish experiences with the Lotus valve system. Due to its unique features, the Lotus valve may improve the prognosis in patients with inoperable or high risk critical aortic stenosis.

Sustained improvement of clinical status and pulmonary hypertension in patients with severe heart failure treated with sildenafil.

BACKGROUND: Sildenafil, a phosphodiesterase-5 inhibitor, has been shown to decrease pulmonary vascular resistance (PVR) in patients with heart failure. The purpose of the study was to evaluate the effect of sildenafil on clinical status and pulmonary vascular reactivity in patients with congestive heart failure. MATERIAL AND METHODS: We enrolled 20 patients (18 men and 2 women, mean age 51 ± 12 years, diagnosed with congestive heart failure and pulmonary hypertension. This was a prospective, single-center study. Patients were treated with sildenafil 25 mg TDS for 12 months. Protocol included NYHA evaluation and repeated echocardiography, cardiac pulmonary stress tests, and right- sided catheterization. RESULTS: Initially, there were 16 (80%) patients in III NYHA status and 4 (20%) patients in II NYHA. After 12 months, 8 patients were in NYHA III (40%) status and 12 patients in NYHA II (60%). Peak oxygen consumption increased from 12 ± 3 ml/kg/min to 19 ± 4 ml/kg/min after 1-year therapy (p<0.001). The cardiac index increased from 3.1 ± 0.6 L/min/m2 to 3.6 ± 0.4 L/min/m2 (p<0.05). Pulmonary vasculature resistance decreased after 1-year therapy (4.7 ± 1 vs. 1.6 ± 0.5 Woods units (p<0.005) comparing to initials. Mean pulmonary artery pressure decreased to 23 ± 6 mmHg from 42 ± 5 mmHg (p<0.001) after 1-year therapy. CONCLUSIONS: One-year sildenafil therapy effectively improved clinical status and pulmonary vascular resistance in patients diagnosed with congestive heart failure.

[Unusual picture of pacemaker leads in patient after Senning procedure]. / Nietypowy uklad elektrod stymulatora u pacjenta po operacji Senninga.

We present a case of a 21-year-old man after Senning operation admitted to our hospital for transvenous implantation of a dual chamber pacemaker. The presence of persistent left superior vena cava enabled us to implant the desired dual chamber pacemaker. It is an extremely unusual situation when two pacemaker leads utilise two different routes to the heart: superior caval vein - atrial baffle - ventricle and persistent left superior caval vein - atrium.

Shortening baroreflex delay in hypertrophic cardiomyopathy patients -- an unknown effect of ß-blockers.

AIMS: Hypertrophic cardiomyopathy (HCM) is characterized by left ventricular hypertrophy and impaired diastolic and systolic function. Abnormal sympathetic-parasympathetic balance is a potential stimulus for left ventricular hypertrophy in HCM patients. ß-Blockers are routinely used in HCM for their strong negative inotropic effect; however, these drugs also influence the sympathetic-parasympathetic balance. This study aimed to determine the autonomic control of the cardiovascular system and the autonomic effects of ß-blockers in HCM patients treated or untreated with ß-blockers. METHODS: Among 51 HCM outpatients (18-70 years old; 29 men) there were 19 individuals with no medication and 32 subjects treated with a ß-blocker. Fourteen age- and gender-matched (23-70 years old; nine men) healthy volunteers were enrolled in the control group. Continuous, non-invasive finger blood pressure was recorded during supine rest for 30 min. Autonomic regulation of the cardiovascular system was measured by heart rate variability and spontaneous baroreflex function (cross-correlation sequence method). RESULTS: The mean pulse interval, time domain and spectral measures of heart rate variability and baroreflex sensitivity were comparable between HCM patients, treated or not with ß-blockers, and the control group. However, the delay of the baroreflex was significantly longer in HCM patients who were not treated with ß-blockers [2.0 (1.6-2.3) s] in comparison with HCM patients receiving ß-blockers [1.4 (1.1-1.8) s; P = 0.0072] or control subjects [1.2 (0.8-1.8) s; P = 0.0025]. This delay did not differ between HCM patients treated with ß-blockers and the control group. CONCLUSIONS: Hypertrophic cardiomyopathy not treated with ß-blockers is accompanied by prolonged baroreflex delay. The use of ß-blockers normalizes this delay.

Evaluation of exercise capacity with cardiopulmonary exercise testing and BNP levels in adult patients with single or systemic right ventricles.

INTRODUCTION: The aim of the study was to evaluate exercise capacity using cardiopulmonary exercise test (CpET) and serum B-type natriuretic peptide (BNP) levels in patients with single or systemic right ventricles. MATERIAL AND METHODS: The study group included 40 patients (16 males) - 17 with transposition of the great arteries after Senning operation, 13 with corrected transposition of the great arteries and 10 with single ventricle after Fontan operation, aged 19-55 years (mean 28.8 ±9.5 years). The control group included 22 healthy individuals (10 males) aged 23-49 years (mean 30.6 ±6.1 years). RESULTS: The majority of patients reported good exercise tolerance - accordingly 27 were classified in NYHA class I (67.5%), 12 (30%) in class II, and only 1 (0.5%) in class III. Cardiopulmonary exercise test revealed significantly lower exercise capacity in study patients than in control subjects. In the study vs. control group VO(2max) was 21.7 ±5.9 vs. 34.2 ±7.4 ml/kg/min (p = 0.00001), maximum heart rate at peak exercise (HRmax) 152.5 ±32.3 vs. 187.2 ±15.6 bpm (p = 0.00001), VE/VCO(2) slope 34.8 ±7.1 vs. 25.7 ±3.2 (p = 0.00001), forced vital capacity (FVC) 3.7 ±0.9l vs. 4.6 ±0.3 (p = 0.03), forced expiratory volume in 1 s (FEV(1)) 3.0 ±0.7 vs. 3.7 ±0.9l (p = 0.0002) respectively. Serum BNP concentrations were higher in study patients than in control subjects; 71.8 ±74.4 vs. 10.7 ±8.1 (pg/ml) respectively (p = 0.00001). No significant correlations between BNP levels and CpET parameters were found. CONCLUSIONS: Patients with a morphological right ventricle serving the systemic circulation and those with common ventricle physiology after Fontan operation show markedly reduced exercise capacity. They are also characterized by higher serum BNP concentrations, which do not however correlate with CpET parameters.

Cardiopulmonary exercise test in the evaluation of exercise capacity, arterial hypertension, and degree of descending aorta stenosis in adults after repair of coarctation of the aorta.

BACKGROUND: Despite effective repair of coarctation of the aorta (CoAo), arterial hypertension (AH) and early coronary artery disease that may result in heart failure. The aim of the study was to evaluate exercise capacity by a cardiopulmonary exercise test in patients after of CoAo repair, and to determine relations between these parameters and the presence of AH, residual stenosis of the descending aorta (AoD) and the patient's age at the time of the surgery. METHODS: 74 patients at mean age 31.2 +/- 9.8 years. The controls: 30 at mean age 32.2 +/- 6.6. Descending aorta (AoD) gradient was evaluated by echocardiography. The group with residual AoD stenosis: >/= 25 mm Hg (AoD+) 32 patients and AoD-: 41 patients. Subgroups without AH (AH-, n = 32), exercise-induced AH (AHex, n = 10), persistent AH (AH+, n = 32). The maximum exercise test was performed. RESULTS: A comparison of the study and control groups: VO(2)max: p = 0.0001), VO(2)max%: p=0.0001 and VE/VCO(2): p = 0.001. Negative correlation: between VO(2)max and the age at the time of surgery: p = 0.004) and a positive: between VE/VCO(2) and age at surgery: p = 0.005. No differences were observed between the AoD+ and AoD- groups with respect to cardiopulmonary parameters. A comparison of the AH+ and AH- groups revealed: VO(2)max: p = 0.01, VO(2)max%: p = 0.02 and VE/VCO(2): p = 0.003. A comparison of the AHex and AH- groups showed VE/VCO(2): p = 0.01. CONCLUSIONS: The exercise capacity of adults after surgical CoAo repair is reduced. This is more pronounced in patients with AH and those operated on at a more advanced age, but not in AoD+. (Cardiol J 2007; 14: 76-82).