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Anderson–Fabry Disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to the progressive accumulation of glycosphingolipids and the structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who, in most cases, are heterozygous with delayed and variable clinical presentation caused by uneven X-chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke, or unexplained cardiomyopathy. Here, we describe a unique case of a homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly, including with alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease led to the discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (p.N215S), which is known to cause predominant cardiac involvement with late onset of the disease. This variant is amenable to oral therapy with the small-molecule chaperone migalastat, which was started and then interrupted due to the recurrence of the patient’s migraine and then re-initiated again after two years. During this period, the patient received enzyme replacement therapy with agalsidase beta but developed progressively worsening venous access. Our case illustrates the importance of the systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom the routine diagnostic process fails to discover Fabry disease, in particular variants with late-onset cardiac manifestations. Many of the late-onset variants are amenable to orally active therapy with migalastat, which significantly improves the comfort of the treatment. Its long-term results are being analyzed by a large international “Follow-me” registry, which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

Abstract COVID‐19 associates with a hypercoagulant state and an increased risk for venous thromboembolic events (VTEs). Whether severe COVID‐19 infection requiring extracorporeal membrane oxygenation (ECMO) support might lead to chronic pulmonary perfusion abnormalities and chronic thromboembolic pulmonary disease/hypertension remains unclear. The purpose of this study was to evaluate chronic pulmonary perfusion abnormalities in long‐term survivors of COVID‐19‐related severe acute respiratory distress syndrome (ARDS) treated by ECMO at our institution. Pulmonary perfusion was examined by ventilation/perfusion (V/Q) single‐photon emission computed tomography or V/Q planar scintigraphy at least 3 months after ECMO explantation, comorbidities and incidence of thromboembolic events were recorded as well. Of 172 COVID‐19 patients treated by ECMO for severe COVID‐19 pneumonia between March 2020 and November 2021, only 80 were successfully weaned from ECMO. Of those, 37 patients were enrolled into the present analysis (27% female, mean age 52 years). Median duration of ECMO support was 12 days. In 24 (65%) patients VTE was recorded in the acute phase (23 patients developed ECMO cannula‐related deep vein thrombosis, 5 of them had also a pulmonary embolism, and one thrombus was associated with a central catheter). The median duration between ECMO explantation and assessment of pulmonary perfusion was 420 days. No segmental or larger mismatched perfusion defects were then detected in any patient. In conclusion, in long‐term survivors of COVID‐19‐related ARDS treated by ECMO, no persistent pulmonary perfusion abnormalities were detected although VTE was common.

Abstract Background Pegunigalsidase alfa is a novel, PEGylated α-galactosidase-A enzyme-replacement therapy approved in the EU and US to treat patients with Fabry disease (FD). Objective/methods BRIDGE is a phase 3 open-label, switch-over study designed to assess safety and efficacy of 12 months of pegunigalsidase alfa (1 mg/kg every 2 weeks) treatment in adults with FD who had been previously treated with agalsidase alfa (0.2 mg/kg every 2 weeks) for ≥ 2 years. Results Twenty-seven patients were screened; 22 met eligibility criteria; and 20 (13 men, 7 women) completed the study. Pegunigalsidase alfa was well-tolerated, with 97% of treatment-emergent adverse events (TEAEs) being of mild or moderate severity. The incidence of treatment-related TEAEs was low, with 2 (9%) discontinuations due to TEAEs. Five patients (23%) reported infusion-related reactions. Overall mean (SD; n = 22) baseline estimated glomerular filtration rate (eGFR) was 82.5 (23.4) mL/min/1.73 m2 and plasma lyso-Gb3 level was 38.3 (41.2) nmol/L (men: 49.7 [45.8] nmol/L; women: 13.8 [6.1] nmol/L). Before switching to pegunigalsidase alfa, mean (standard error [SE]) annualized eGFR slope was − 5.90 (1.34) mL/min/1.73 m2/year; 12 months post-switch, the mean eGFR slope was − 1.19 (1.77) mL/min/1.73 m2/year; and mean plasma lyso-Gb3 reduced by 31%. Seven (35%) out of 20 patients were positive for pegunigalsidase alfa antidrug antibodies (ADAs) at ≥ 1 study timepoint, two of whom had pre-existing ADAs at baseline. Mean (SE) changes in eGFR slope for ADA-positive and ADA-negative patients were + 5.47 (3.03) and + 4.29 (3.15) mL/min/1.73 m2/year, respectively, suggesting no negative impact of anti-pegunigalsidase alfa ADAs on eGFR slope. Conclusion Pegunigalsidase alfa may offer a safe and effective treatment option for patients with FD, including those previously treated with agalsidase alfa. TRN: NCT03018730. Date of registration: January 2017.

Abstract Aims Fabry disease (FD) is a rare X‐linked genetic disorder caused by α‐galactosidase A (AGALA) deficiency. Whereas ‘classic’ variant has multisystemic manifestation, the more recently described ‘later‐onset’ variant is characterized by predominant cardiac involvement that often mimics hypertrophic cardiomyopathy (HCM). Methods and results Consecutive unrelated patients with HCM were screened for FD in 16 (out of 17) cardiac centres in the Czech Republic covering specialized cardiology care from June 2017 to December 2018. AGALA activity and globotriaosylsphingosine (lyso‐Gb3) levels were measured in all subjects using the dry blood spot method. FD was suspected in male patients with AGALA activity 3.5 ng/mL. Positive screening results were confirmed by genetic testing. We evaluated 589 patients (390 males, 66%) with HCM (mean maximal myocardial thickness 19.1 ± 4.3 mm). The average age was 58.4 ± 14.7 years. In total, 17 patients (11 males, 6 females) had a positive screening result, and subsequently, six of them (four males and two females) had a genetically confirmed pathogenic GLA mutation (total prevalence of 1.02%). Five of these patients were carrying the p.N215S mutation known to cause a typical later‐onset cardiac FD. Conclusions We confirmed the prevalence of FD repeatedly reported in previous screening programmes (approximately 1% irrespective of gender) in a non‐selected HCM population in Central Europe. Our findings advocate a routine screening for FD in all adult patients with HCM phenotype including both genders. The dry blood spot method used led to identification of clearly pathogenic variants.

BackgroundHypertension is the most common cardiovascular disease which substantially increases cardiovascular morbidity and mortality. Despite the broad availability of antihypertensive medication, control of hypertension is not satisfactory worldwide.ObjectiveThe study aim was to assess longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension in a representative population sample of the Czechia from 1985 to 2016/2017, focusing on sex differences.MethodsA total of 7,606 men and 8,050 women aged 25–64 years were screened for major CV risk factors in seven independent cross-sectional surveys run consistently in the same six country districts of the Czechia between 1985 and 2016/2017. The population samples were randomly selected.ResultsOver a study period of 31/32 years, there was a significant decline in systolic and diastolic blood pressure in both sexes, whereas the prevalence of hypertension decreased only in women. There was an increase in hypertension awareness in both sexes over the entire study period with consistently higher rates in women. The proportion of individuals treated with antihypertensive drugs increased significantly in both sexes throughout the study, again with consistently higher rates in women. Control of hypertension increased significantly over the study period with consistently higher rates in women. The age-adjusted trends in blood pressure, prevalence, awareness, and treatment of hypertension were significantly different in men and women, always in favor of women. The age-adjusted trends in control of hypertension in treated patients were equally poor in both sexes.ConclusionThere are significant differences in longitudinal trends in blood pressure, prevalence, awareness, treatment, and control of hypertension between men and women, always in favor of women except for the control of hypertension in treated patients, where it is equally poor in both sexes.

Background: Severe hypercholesterolemia is associated with an increase in the risk of developing atherosclerotic cardiovascular disease. The aim of this analysis was to assess longitudinal trends in severe dyslipidemia (defined as total cholesterol > 8 mmol/L or LDL-cholesterol > 5 mmol/L) in a representative population sample of the Czech Republic and to analyze the longitudinal trends in the basic characteristics of individuals with severe dyslipidemia. Methods: Seven independent cross-sectional surveys were organized in the Czech Republic to screen for major cardiovascular risk factors (from 1985 to 2015–2018). A total of 20,443 randomly selected individuals aged 25–64 years were examined. Results: The overall prevalence of severe dyslipidemia was 6.6%, with a significant downward trend from the fifth survey onwards (2000/2001). Over the study period of 30+ years, the individuals with severe dyslipidemia became older, increased in BMI, and did not change their smoking habits. Total cholesterol and non-HDL-cholesterol decreased significantly in both sexes throughout the duration of the study. Conclusions: Despite a significant improvement in lipids in the Czech Republic from 1985, substantially contributing to the decline in cardiovascular mortality, the number of individuals with severe dyslipidemia remained high, and in most cases, they were newly detected during our screening examinations and were thus untreated.

Abstract Giant cell myocarditis is a rare form of autoimmune myocarditis with high morbidity and mortality that affects mainly middle‐aged adults. We report a case study of a 70‐year‐old man on chronic immunosuppression who presented with sustained ventricular tachycardia and symptoms of acute systolic heart failure, both with poor response to standard measures. A decision to pursue endomyocardial biopsy established the diagnosis of GCM and lead to initiation of immunosuppressive therapy and a favourable outcome. Our case illustrates that a low threshold for endomyocardial biopsy in new onset heart failure can lead to actionable information even in patients of advanced age.

Abstract Aims Long‐term treatment effect studies in large female Fabry patient groups are challenging to design because of phenotype heterogeneity and lack of appropriate comparison groups, and have not been reported. We compared long‐term cardiomyopathy and kidney function outcomes after agalsidase beta treatment with preceding treatment‐naive outcomes. Methods and results Self‐controlled pretreatment and post‐treatment comparison (piecewise mixed linear modelling) included Fabry female patients ≥18 years at treatment initiation who received agalsidase beta (0.9–1.1 mg/kg every other week) for ≥2 years, with ≥2 pretreatment and ≥2 post‐treatment outcome measurements during 10‐year follow‐up. Left ventricular posterior wall thickness (LVPWT)/interventricular septal thickness (IVST) and estimated glomerular filtration rate (eGFR, Chronic Kidney Disease Epidemiology Collaboration creatinine equation) analyses included 42 and 86 patients, respectively, aged 50.0 and 46.3 years at treatment initiation, respectively. LVPWT and IVST increased pretreatment (follow‐up 3.5 years) but stabilized during 3.6 years of treatment (LVPWT: n = 38, slope difference [95% confidence interval (CI)] = −0.41 [−0.68, −0.15] mm/year, Ppre–post difference

Purpose: Primary aldosteronism (PA) is considered the most common form of secondary hypertension, however, its prevalence, particularly in a general population, is still a matter of debate. The aim of our study was to evaluate the prevalence of PA in a randomly selected general population sample. Materials and methods: A total of 1940 individuals (1% population random sample) aged 25–64 years were screened for major cardiovascular risk factors in six districts of the Czech Republic. Hypertension was defined as a mean of two blood pressure readings ≥140/90 mmHg at one visit or taking antihypertensive medication. Within this population, 740 individuals were labelled as hypertensives and 650 of them sampled for the analysis of direct plasma renin and serum aldosterone. The diagnosis of PA was based on elevated serum aldosterone, low plasma renin and high aldosterone/renin (ARR) ratio and was also verified by a confirmatory test with saline infusion. Results: Positive ARR was found in 52 (8%) individuals (64% women, 36% men, however, due to substatntial proportion of reluctatnt participants to undergo a further work-up (27%), we could confirm the diagnosis of PA only in 13 of them (2%). Aldosterone-producing adenoma was found in one case only, seven patients had idiopathic type and five individuals refused potential surgical treatment therefore, adrenal venous sampling was not performed. Conclusion: Elevated serum aldosterone together with low renin and high ARR were found in 52 (8%) of hypertensives selected from a general population sample, however, the diagnosis of PA was confirmed only in 13 of them (2%). This study based on a general population survey highlighted the difficulty of conducting epidemiological studies on primary aldosteronism in a relatively healthy cohort part of whom did not provide the level of collaboration that is necessary to assess the true prevalence of this condition.

Abstract This study investigated the epidemiology and survival outcomes of chronic thromboembolic pulmonary hypertension (CTEPH) in the Czech Republic, wherein pulmonary endarterectomy (PEA) surgery was the only targeted treatment option until 2015. This study included all consecutive adults newly diagnosed with CTEPH in the Czech Republic between 2003 and 2016. Incidence/prevalence rates were calculated using general population data extracted from the Institute of Health Information and Statistics of the Czech Republic. Kaplan–Meier estimates of survival from diagnosis until 2018 were calculated. Of a total of 453 patients observed, 236 (52.1%) underwent PEA (median time from diagnosis to PEA: 2.9 months) and 71 (34.1%) had residual pulmonary hypertension (PH) post‐PEA. CTEPH incidence rate (95% confidence interval [CI]) between 2006 and 2016 was 4.47 (4.05; 4.91) patients per million (ppm) per year, and the prevalence (95% CI) was 37.43 (33.46; 41.73) ppm in 2016. The rate of CTEPH‐related hospitalizations (95% CI) per 100 person‐years was 24.4 (22.1; 26.9) for operated patients and 34.2 (30.9; 37.7) for not‐operated patients. Median overall survival (95% CI) for all patients from CTEPH diagnosis was 11.2 (9.4; not reached) years. Five‐year survival probability (95% CI) was 95.3% (89.9; 97.9) for operated patients without residual PH, 86.3% (75.3; 92.7) for operated patients with residual PH and 61.2% (54.0; 67.6) for not‐operated patients. This study reported epidemiological estimates of CTEPH in the Czech Republic consistent with estimates from other national systematic registries; and indicates an unmet medical need in not‐operated patients and operated patients with residual PH.

Oxidative stress and inflammation contribute significantly to atherogenesis. We and others have demonstrated that mildly elevated serum bilirubin levels protect against coronary and peripheral atherosclerosis, most likely due to the antioxidant and anti-inflammatory activities of bilirubin. The aim of the present study was to assess serum bilirubin and the markers of oxidative stress and inflammation in both healthy subjects and patients with various forms of atherosclerosis. The study was performed in patients with premature myocardial infarction (n = 129), chronic ischemic heart disease (n = 43), peripheral artery disease (PAD, n = 69), and healthy subjects (n = 225). In all subjects, standard serum biochemistry, UGT1A1 genotypes, total antioxidant status (TAS), and concentrations of various pro- and anti-inflammatory chemokines were determined. Compared to controls, all atherosclerotic groups had significantly lower serum bilirubin and TAS, while having much higher serum high-sensitivity C-reactive protein (hsCRP) and most of the analyzed proinflammatory cytokines (p < 0.05 for all comparisons). Surprisingly, the highest inflammation, and the lowest antioxidant status, together with the lowest serum bilirubin, was observed in PAD patients, and not in premature atherosclerosis. In conclusion, elevated serum bilirubin is positively correlated with TAS, and negatively related to inflammatory markers. Compared to healthy subjects, patients with atherosclerosis have a much higher degree of oxidative stress and inflammation.

Background and aimsFabry disease (FD) is a rare X-linked lysosomal storage disorder caused by disease-associated variants in the alpha-galactosidase A gene (GLA). FD is a known cause of stroke in younger patients. There are limited data on prevalence of FD and stroke risk in unselected stroke patients.MethodsA prospective nationwide study including 35 (78%) of all 45 stroke centers and all consecutive stroke patients admitted during three months. Clinical data were collected in the RES-Q database. FD was diagnosed using dried blood spots in a stepwise manner: in males-enzymatic activity, globotriaosylsphingosine (lyso-Gb3) quantification, if positive followed by GLA gene sequencing; and in females GLA sequencing followed by lyso-Gb3.Results986 consecutive patients (54% men, mean age 70 years) were included. Observed stroke type was ischemic 79%, transient ischemic attack (TIA) 14%, intracerebral hemorrhage (ICH) 7%, subarachnoid hemorrhage 1% and cerebral venous thrombosis 0.1%. Two (0.2%, 95% CI 0.02-0.7) patients had a pathogenic variant associated with the classical FD phenotype (c.1235_1236delCT and p.G325S). Another fourteen (1.4%, 95% CI 0.08-2.4) patients had a variant of GLA gene considered benign (9 with p.D313Y, one p.A143T, one p.R118C, one p.V199A, one p.R30K and one p.R38G). The index stroke in two carriers of disease-associated variant was ischemic lacunar. In 14 carriers of GLA gene variants 11 strokes were ischemic, two TIA, and one ICH. Patients with positive as compared to negative GLA gene screening were younger (mean 60±SD, min, max, vs 70±SD, min, max, P = 0.02), otherwise there were no differences in other baseline variables.ConclusionsThe prevalence of FD in unselected adult patients with acute stroke is 0.2%. Both patients who had a pathogenic GLA gene variant were younger than 50 years. Our results support FD screening in patients that had a stroke event before 50 years of age.

BACKGROUND:Compared with Western Europe, the decline in cardiovascular (CV) mortality has been delayed in former communist countries in Europe, including the Czech Republic. We have assessed longitudinal trends in major CV risk factors in the Czech Republic from 1985 to 2016/17, covering the transition from the totalitarian regime to democracy. METHODS:There were 7 independent cross-sectional surveys for major CV risk factors conducted in the Czech Republic in the same 6 country districts within the WHO MONICA Project (1985, 1988, 1992) and the Czech post-MONICA study (1997/98, 2000/01, 2007/08 and 2016/2017), including a total of 7,606 males and 8,050 females. The population samples were randomly selected (1%, aged 25-64 years). RESULTS:Over the period of 31/32 years, there was a significant decrease in the prevalence of smoking in males (from 45.0% to 23.9%; p < 0.001) and no change in females. BMI increased only in males. Systolic and diastolic blood pressure decreased significantly in both genders, while the prevalence of hypertension declined only in females. Awareness of hypertension, the proportion of individuals treated by antihypertensive drugs and consequently hypertension control improved in both genders. A substantial decrease in total cholesterol was seen in both sexes (males: from 6.21 ± 1.29 to 5.30 ± 1.05 mmol/L; p < 0.001; females: from 6.18 ± 1.26 to 5.31 ± 1.00 mmol/L; p < 0.001). CONCLUSIONS:The significant improvement in most CV risk factors between 1985 and 2016/17 substantially contributed to the remarkable decrease in CV mortality in the Czech Republic.

Pharmacokinetic data for riociguat in patients with chronic thromboembolic pulmonary hypertension (CTEPH) have previously been reported from randomized clinical trials, which may not fully reflect the population encountered in routine practice. The aim of the current study was to characterize the pharmacokinetic of riociguat and its metabolite M1 in the patients from routine clinical practice. A population pharmacokinetic model was developed in NONMEM 7.3, based on riociguat and its metabolite plasma concentrations from 49 patients with CTEPH. One sample with riociguat and M1 concentrations was available from each patient obtained at different time points after last dose. Age, bodyweight, sex, smoking status, concomitant medications, kidney and liver function markers were tested as potential covariates of pharmacokinetic of riociguat and its metabolite. Riociguat and M1 disposition was best described with one-compartment models. Apparent volume of distribution (Vd/F) for riociguat and M1 were assumed to be the same. Total bilirubin and creatinine clearance were the most predictive covariates for apparent riociguat metabolic clearance to M1 (CL f,M1 /F) and for apparent riociguat clearance through remaining pathways (CL e,r /F), respectively. CL f,M1 /F, CL e,r /F, Vd/F of riociguat and M1, and clearance of M1 (CL e,M1 /F) for a typical individual with 70 mL/min creatinine clearance and 0.69 mg/dL total bilirubin were 0.665 L/h (relative standard error = 17%)), 0.66 (18%) L/h, 3.63 (15%) L and 1.47 (19%) L/h, respectively. Upon visual identification of six outlying individuals, an absorption lag-time of 2.95 (6%) h was estimated for these patients. In conclusion, the only clinical characteristics related to riociguat exposure in patients with CTEPH from routine clinical practice are total bilirubin and creatinine clearance. This confirms the findings of the previous population pharmacokinetic studies based on data from randomized clinical trials.

Abstract Background Renal denervation (RDN) is a promising therapeutic method in cardiology. Its currently most investigated indication is resistant hypertension. Other potential indications are atrial fibrillation, type 2 diabetes mellitus and chronic renal insufficiency among others. Previous trials showed conflicting but promising results, but the real benefits of RDN are still under investigation. Patients with renal insufficiency and resistant hypertension are proposed to be a good target for this therapy due to excessive activation of renal sympathetic drive. However, only limited number of studies showed benefits for these patients. We hypothesize that in our experimental model of chronic kidney disease (CKD) due to ischemia with increased activity of the renin–angiotensin–aldosterone system (RAAS), renal denervation can have protective effects by slowing or blocking the progression of renal injury. Methods An experimental biomodel of chronic renal insufficiency induced by ischemia was developed using selective renal artery embolization (remnant kidney porcine model). 27 biomodels were assessed. Renal denervation was performed in 19 biomodels (denervated group), and the remaining were used as controls (n = 8). The extent of renal injury and reparative process between the two groups were compared and assessed using biochemical parameters and histological findings. Results Viable remnant kidney biomodels were achieved and maintained in 27 swine. There were no significant differences in biochemical parameters between the two groups at baseline. Histological assessment proved successful RDN procedure in all biomodels in the denervated group. Over the 7-week period, there were significant increases in serum urea, creatinine, and aldosterone concentration in both groups. The difference in urea and creatinine levels were not statistically significant between the two groups. However, the level of aldosterone in the denervated was significantly lower in comparison to the controls. Histological assessment of renal arteries showed that RDN tends to produce more damage to the arterial wall in comparison to vessels in subjects that only underwent RAE. In addition, the morphological damage of kidneys, which was expressed as a ratio of damaged surface (or scar) to the overall surface of kidney, also did not show significant difference between groups. Conclusions In this study, we were not able to show significant protective effect of RDN alone on ischemic renal parenchymal damage by either laboratory or histological assessments. However, the change in aldosterone level shows some effect of renal denervation on the RAAS system. We hypothesize that a combined blockade of the RAAS and the sympathetic system could provide more protective effects against acute ischemia. This has to be further investigated in future studies.

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Keywords: Fabry disease, agalsidase alfa, agalsidase beta, systematic literature review, enzyme replacement therapy, adult male patients

Introduction. Extracorporeal cardiopulmonary resuscitation (ECPR) is a challenging approach for treating refractory out-of-hospital cardiac arrest (OHCA). Case Presentation. The authors describe a case of a 40-year-old Caucasian female who suffered from refractory OHCA, was admitted to a hospital while receiving ongoing cardiopulmonary resuscitation, and was connected to venoarterial extracorporeal membrane oxygenation 73 minutes after collapse. Ventricular tachyarrhythmias alternating with pulseless electrical activity resolved after eight hours. Following complete cardiac and neurological recovery, only adenoviral genome was found in myocardial biopsy. After 11 months, another episode of identical arrhythmias was rescued by an implantable cardioverter-defibrillator. Conclusion. Adequate prehospital and early hospital logistics is a prerequisite for successfully implementing extracorporeal cardiopulmonary resuscitation for refractory OHCA.

Erectile dysfunction significantly affects quality of life in young men. Authors have evaluated erectile function in men with coronary artery disease (CAD) and the relationship between the degree of erectile dysfunction (ED) and the age of their first acute myocardial infarction (AMI). The incidence of erectile dysfunction in three groups of patients of AMI survivors was investigated: AMI survivors younger than 45 years, AMI survivors older than 65 years, and normal male population aged between 30 and 60 years. Erectile function was assessed by the International Index of Erectile Function (IIEF-5) questionnaire. In post-AMI male patients younger than 45 years ( n = 76), mild ED occurred in 26% and severe in 7%. In the older AMI group, mild ED occurred in 52% and severe in 38%. In the control group age matched to younger survivors, 96% denied ED and only one control patient had a score of 20 on the IIEF-5. A paradoxical result was observed in patients using beta blockers (BB), who had better scores than the group without BB. Statin treatment had a positive influence on the score in questionnaires. Those on statins had an average score of 21.0 ± 4.9 vs. without statin 17.7 ± 5.7, p = .03. The current findings identified that the prevalence of ED is relatively high in young patients with CAD and is related to treatment of the CAD. The overall increase in ED presence suggests that the background of their coronary event is not due to destabilization of single focused atheroma but may reflect a generalized atherosclerotic process.

[This corrects the article DOI: 10.1371/journal.pone.0166290.].

Serum uric acid (UA) elevation is common in patients with cardiovascular, renal and metabolic diseases. However, no study to date has analysed the role of UA in Fabry disease (FD).To evaluate the association between serum UA levels and mortality and morbidity in FD.We conducted a post-hoc analysis of a prospectively followed-up cohort of 124 patients with genetically proven FD. Serum UA levels were acquired at baseline; clinical events and mortality were assessed during regular visits every 6 to 12 months. The primary endpoint was a composite of multiple secondary outcomes: all-cause mortality, adverse cardiovascular events, progression of renal dysfunction and stroke or transient ischaemic attack (TIA). Predictive value was assessed using the Cox proportional hazards model and the Kaplan Meyer estimator.During follow-up of 7.4 ± 3.7 years, 64 (52%) patients reached the primary combined endpoint. Overall, UA levels were significantly associated with combined outcome (p < 0.001) and remained independently associated after correcting for age, sex and estimated glomerular filtration rate (hazard ratio [HR] per 20 μmol/l increase 1.09, 95% confidence interval [95%CI] (1.00-1.19), p = 0.04). UA was associated with overall mortality in univariate analysis (p = 0.021); however, the association did not reach statistical significance after multivariate correction (HR per 20 μmol/l increase 1.07 95%CI 0.93-1.25, p = 0.32). Higher UA levels were also associated with cardiac adverse outcomes, progression of left ventricular hypertrophy and progression of renal dysfunction (ps < 0.001). No association was observed between UA levels and stroke or TIA (p = 0.323).Increased serum UA levels may represent an independent risk factor for adverse clinical outcomes in Fabry patients and are associated with all-cause mortality. UA is a widely available and cheap biomarker that may improve risk stratification of Fabry patients in clinical practice.

Saphenopopliteal junction classification has been developing, but still the precise knowledge of junction type is crucial for proper surgical treatment. We examined the saphenopopliteal junction by duplex venous scanning in 244 extremities in healthy volunteers (median age: 23.0 years, 83 females, 39 male) and performed a meta-analysis of 13 studies focusing on structural types of the junction. According to Schweighoffer's classification we distinguished 5 types of the junction and we subdivided type A according to Cavezzi's classification of gastrocnemial veins termination into two. We added type F (small saphenous vein-SSV terminates into popliteal vein-PV), described especially in cadaveric studies. In our study, the most frequent type was A1 (96 cases), followed by C (70), B (48), A2 (20), E (6), D (3) and F (0). The pooled prevalence estimate for types A + B + D + E was 54.7% (95% CI 40.9–69.6%) and for type C 24.4% (95% CI 19.3–29.5%), whereas in 17.1% (95% CI 6.3–27.9%) of cases, the SSV terminated in the PV with no cranial extension present. The knowledge of the saphenopopliteal junction and its variations prevalence can help clinicians to quickly identify the real type of the junction during routine examination. In mid-European population, the main type is A1 and worldwide type A. [ABSTRACT FROM AUTHOR]