Ambulatory Blood Pressure Monitoring as a Useful Tool in the Cardiological Assessment of Pancreas Transplant Recipients with Type 1 Diabetes.

Having the appropriate tools to identify pancreas recipients most susceptible to coronary artery disease (CAD) is crucial for pretransplant cardiological assessment. The aim of this study is to evaluate the association between blood pressure (BP) indices provided by ambulatory blood pressure monitoring (ABPM) and the prevalence of CAD in pancreas transplant candidates with type 1 diabetes (T1D). This prospective cross-sectional study included adult T1D patients referred for pretransplant cardiological assessment in our center. The study population included 86 participants with a median age of 40 (35-46) years. In multivariate logistic regression analyses, after adjusting for potential confounding factors, higher 24 h BP (systolic BP/diastolic BP/pulse pressure) (OR = 1.063, 95% CI 1.023-1.105, p = 0.002/OR = 1.075, 95% CI 1.003-1.153, p = 0.042/OR = 1.091, 95 CI 1.037-1.147, p = 0.001, respectively) and higher daytime BP (systolic BP/diastolic BP/pulse pressure) (OR = 1.069, 95% CI 1.027-1.113, p = 0.001/OR = 1.077, 95% CI 1.002-1.157, p = 0.043/OR = 1.11, 95% CI 1.051-1.172, p = 0.0002, respectively) were independently and significantly associated with the prevalence of CAD. Daytime pulse pressure was the strongest indicator of the prevalence of CAD among all analyzed ABPM parameters. ABPM can be used as a valuable tool to identify pancreas recipients who are most susceptible to CAD. We suggest the inclusion of ABPM in pretransplant cardiac screening in type 1 diabetes patients eligible for pancreas transplantation.

Efficacy of Catheter Ablation Using the Electroanatomical System without the Use of Fluoroscopy in Patients with Ventricular Extrasystolic Beats.

BACKGROUND: Catheter ablation (CA) has become safe and efficient for the treatment of patients with ventricular extrasystolic beats (VEBs). The three-dimensional electroanatomic mapping (EAM) system allows the elimination of fluoroscopy time during CA procedures. Non-fluoroscopy CA is a challenging procedure requiring intimate knowledge of cardiac anatomy in patients with VEBs. The study aimed to evaluate the efficacy and safety of the non-fluoroscopy CA using the EAM system in patients with VEBs. METHODS: Completely fluoroless CA of VEBs guided by EAM was performed in 86% (94 out of 109) of consecutive patients with VEBs. The remaining 15 patients underwent conventional fluoroscopy-guided CA. Demographic and clinical baseline characteristics, procedure parameters, and following complications were obtained from the medical records. Primary outcomes were the acute procedural success rate, the permanent success rate (6-month follow-up), complications, and procedure time. RESULTS: There were no significant differences between groups regarding baseline characteristics. Acute procedural success was achieved in 85 patients (90%) in the non-fluoroscopy group and in 14 patients (93%) in the fluoroscopy group (ns). A long-term success rate was achieved in 82 patients (87%) in the non-fluoroscopy group and in 14 (82%) patients in the fluoroscopy group (ns). The median procedure time was 85 min in the non-fluoroscopy group and 120 min in the fluoroscopy group (p = 0.029). There was only one major complication in the non-fluoroscopy group (ns). CONCLUSIONS: Completely fluoroless CA of VEBs guided by EAM is a feasible, safe, and efficient procedure.

Neuron-Specific Enolase and S100B: The Earliest Predictors of Poor Outcome in Cardiac Arrest.

Background: Proper prognostication is critical in clinical decision-making following out-of-hospital cardiac arrest (OHCA). However, only a few prognostic tools with reliable accuracy are available within the first 24 h after admission. Aim: To test the value of neuron-specific enolase (NSE) and S100B protein measurements at admission as early biomarkers of poor prognosis after OHCA. Methods: We enrolled 82 consecutive patients with OHCA who were unconscious when admitted. NSE and S100B levels were measured at admission, and routine blood tests were performed. Death and poor neurological status at discharge were considered as poor clinical outcomes. We evaluated the optimal cut-off levels for NSE and S100B using logistic regression and receiver operating characteristic (ROC) analyses. Results: High concentrations of both biomarkers at admission were significantly associated with an increased risk of poor clinical outcome (NSE: odds ratio [OR] 1.042 per 1 ng/dL, [1.007−1.079; p = 0.004]; S100B: OR 1.046 per 50 pg/mL [1.004−1.090; p < 0.001]). The dual-marker approach with cut-off values of ≥27.6 ng/mL and ≥696 ng/mL for NSE and S100B, respectively, identified patients with poor clinical outcomes with 100% specificity. Conclusions: The NSE and S100B-based dual-marker approach allowed for early discrimination of patients with poor clinical outcomes with 100% specificity. The proposed algorithm may shorten the time required to establish a poor prognosis and limit the volume of futile procedures performed.

The Impact of an Elevated Uric Acid Level on the Prevalence of Coronary Artery Disease in Pancreas Transplant Candidates with Type 1 Diabetes: A Cross Sectional Study.

Pancreas transplantation is considered a high-risk surgery with cardiovascular complications. Early detection of all potential cardiovascular risk factors can decrease the perioperative risk and improve the pancreas recipients' outcome. The present study aims to evaluate the association between serum uric acid (UA) levels and the prevalence of coronary artery disease (CAD) in patients eligible for pancreas transplantation. We prospectively enrolled 63 consecutive patients with type 1 diabetes (T1D) who underwent cardiological evaluation before pancreas transplantation in our center. Participants underwent clinical evaluation, laboratory assays, and coronary angiography. The median concentration of UA in patients with CAD was significantly higher than in participants without CAD (6.43 (4.93-7.26) vs. 4.41 (3.64-5.49) mg/dL, p = 0.0002). We showed the positive correlation between UA concentration and systolic blood pressure, pulse pressure (PP) and triglycerides (r = 0.271, p = 0.032; r = 0.327, p = 0.009; r = 0.354, p = 0.004, respectively). In a multivariate analysis, the concentration of UA (OR 2.044; 95% CI: 1.261-3.311, p = 0.004) was independently associated with the prevalence of CAD in pancreas transplant candidates with T1D. We demonstrated that elevated UA levels were strongly associated with the high prevalence of CAD in pancreas transplant candidates with T1D. To stratify cardiovascular risk, the measurement of the UA concentration should be considered in all T1D patients qualified for pancreas transplantation.

Vitamin D Deficiency as a Predictor of a High Prevalence of Coronary Artery Disease in Pancreas Transplant Candidates With Type 1 Diabetes.

Introduction: Pancreas transplantation is a high-risk procedure in terms of cardiovascular complications. Therefore, identification of all cardiovascular risk factors is crucial to prevent cardiovascular complications after pancreas transplantation. Vitamin D deficiency (VDD) appears to be a potential risk factor for coronary artery disease. Objective: To determine the prevalence of VDD in pancreas transplant candidates, and further to examine the relationship between vitamin D and the prevalence of coronary artery disease and lipid profile parameters. Materials and Methods: This is a prospective cross-sectional study. We enrolled consecutive patients with type 1 diabetes eligible for simultaneous pancreas-kidney transplantation or pancreas transplant alone. The laboratory tests included HbA1c, lipid profile, creatinine, and total 25-hydroxyvitamin D (25(OH)D). The diagnosis of coronary artery disease was based on coronary angiography. Results: The study population included 48 patients. VDD was revealed in 48% of patients and coronary artery disease in 35% of patients. The mean concentration of vitamin D in the entire cohort was 21.3 ± 9.48 ng/ml. The median value of 25(OH)D in patients with coronary artery disease was significantly lower than in patients without coronary artery disease (18.5 (11.6-21.5) vs. 24.8 (18.4-31.8) ng/ml, p = 0.018). There was a significant relationship between VDD and coronary artery disease (OR = 4.36; 95% confidence interval (CI): 1.22-15.64, p = 0.034). A patient's odds of having coronary artery disease while having a sufficient level of vitamin D was 4.36 times lower than if the patient had VDD. There was a significant relationship between VDD and hypertension (OR = 5.91; 95% CI: 1.12-31.20, p = 0.039) and hemodialysis (OR = 4.25; 95% CI: 1.25-14.5, p = 0.023). There was no significant correlation between 25(OH)D and lipid profile. Conclusions: VDD is highly prevalent in pancreas transplant candidates with type 1 diabetes. There is a significant relationship between VDD and increased prevalence of coronary disease. The lack of any significant association between serum vitamin D and lipid profile suggests that the relationship between vitamin D and coronary artery disease results from other causes.

Neuron-specific enolase concentrations for the prediction of poor prognosis of comatose patients after out-of-hospital cardiac arrest: an observational cohort study.

BACKGROUND: Neuron-specific enolase (NSE) is a biomarker for neurological outcomes after cardiac arrest with the most evidence collected thus far; however, recommended prognostic cutoff values are lacking owing to the discrepancies in the published data. AIMS: The aim of the study was to establish NSE cutoff values for prognostication in the environment of a cardiac intensive care unit following out-of-hospital cardiac arrest (OHCA). METHODS: A consecutive series of 82 patients admitted after OHCA were enrolled. Blood samples for the measurement of NSE levels were collected at admission and after 1 hour, 3, 12, 24, 48, and 72 hours. Neurological outcomes were quantified using the cerebral performance category (CPC) index. Each patient was classified into either the good (CPC ≤2) or poor prognosis (CPC ≥3) group. RESULTS: Median NSE concentrations were higher in the poor prognosis group, and the difference reached statistical significance at 48 and 74 hours (84.4 ng/ml vs 22.9 ng/ml at 48 hours and 152.1 ng/ml vs 18.7 ng/ml at 72 hours; P <0.001, respectively). Moreover, in the poor prognosis group, NSE increased significantly between 24 and 72 hours (P <0.001). NSE cutoffs for the prediction of poor prognosis after OHCA were 39.8 ng/ml, 78.7 ng/ml, and 46.2 ng/ml for 24, 48, and 72 hours, respectively. The areas under the curve were significant at each time point, with the highest values at 48 and 72 hours after admission (0.849 and 0.964, respectively). CONCLUSIONS: Elevated NSE concentrations with a rise in levels in serial measurements may be utilized in the prognostication algorithm after OHCA.

Two Strategies for the Dosage of Acenocoumarol Co-Administered with Rifampicin in Staphylococcal Prosthetic Valve Endocarditis.

According to current European Society of Cardiology guidelines, for staphylococcal prosthetic valve endocarditis, rifampicin should be one of the drugs used. However, there is a concomitant need for vitamin K antagonists in patients with mechanical prostheses. It is widely known that rifampicin interacts with vitamin K antagonists (VKA), and this interaction makes it difficult to maintain the INR (international normalized ratio) value in the therapeutic range. We present two clinical cases of staphylococcal prosthetic valve endocarditis patients. Two different strategies for dealing with adverse drug interactions have been applied. In the first case, the dose of warfarin was up-titrated until the optimal INR value was obtained. In the second case, due to the history of labile INR values, a decision was made to modify the dosage of warfarin, taking into account pharmacological aspects of drug interactions.

Is there heart disease in cases of neurodegeneration associated with mutations in C19orf12?

INTRODUCTION: In mitochondrial membrane protein-associated neurodegeneration (MPAN), a subtype of neurodegeneration with brain iron accumulation (NBIA), patients suffer from optic nerve atrophy and dementia, which are also typical for another group of diseases, the mitochondrial diseases (MD). Around 30% of patients with MD have heart disease, commonly cardiomyopathy and arrhythmias, and 10% experience a major adverse cardiovascular event. The aim of this study was to assess cardiac involvement in MPAN. METHODS: Thirteen patients with MPAN were evaluated after written informed consent. All patients had echocardiography and 12 patients had 24-h Holter electrocardiogram (ECG) monitoring using 3-channel digital recorders. RESULTS: Echocardiography revealed normal values for the dimensions of all heart chambers. The systolic function of the left ventricle was normal in all cases. Right ventricle systolic impairment was found in three patients. 24-hour Holter ECG revealed predominant resting tachycardia during daytime with no physiological slowing of heart rate during sleep in seven cases. No significant arrhythmias were found. In nine patients, selected heart rate variability (HRV) parameters were lower than reference values. CONCLUSION: Cardiomyopathy, typical of MD, was not found in patients with MPAN. There were no significant arrhythmias, but disturbances in the circadian rhythm of the heart rate were observed in most cases. The decrease in HRV may reflect an early sign of autonomic dysfunction. A standard cardiac work-up is recommended for patients with MPAN to assess if additional treatment is needed.

Clinicopathological characteristics of breast cancer patients with NOD2 mutation according to age.

INTRODUCTION: The purpose of the present study was to characterise patients with breast cancer (BC) and NOD2-mutation (age ≥ 50 years) according to their clinicopathological factors or family history. Patients aged ≥ 50 years were compared with the control group and with NOD2-mutation carriers aged < 50 years. MATERIAL AND METHODS: Prognostic factors were analysed in patients with BC with confirmed NOD2 c.3016_3017insC (n = 150) mutations. The control group was selected from patients with BC without mutations (n = 376). RESULTS: There were significant differences between NOD2-mutation carriers and the control group aged ≥ 50 years, according to HER2 overexpression (p = 0.0001), ER (-) (p = 0.007), PR (-) (p = 0.003), T1-T2 (p = 0.011), and G3 (p = 0.036). Similarly, significant differences were observed between NOD2-mutation carriers and the control group aged < 50 years, according to HER2 overexpression (p = 0.0001), ER (-) (p = 0.049), and N (+) (p = 0.038). In patients aged ≥ 50 years, family history of cancer, including BC, was observed more often in NOD2-mutation carriers compared with the control group of patients (OR = 1.66; p = 0.072, for BC in family history: OR = 2.65; p = 0.002). NOD2-mutation carriers aged ≥ 50 years had significantly less frequent G3 (p = 0.004) and HER2 overexpression (p = 0.043) compared with patients with NOD2 mutation aged < 50 years. CONCLUSIONS: The presence of the NOD2 mutation is not only characteristic of younger patients but also in patients > 50 years of age. In NOD2-mutation carriers aged ≥ 50 years, the presence of larger tumour size, G3, or HER2 overexpression were lower compared with younger patients with NOD2 mutation.

Influence of heart rate on FFR measurements: An experimental and clinical validation study.

BACKGROUND: Functional lesion assessment in stable coronary disease is considered the gold standard. The result of fractional flow reserve (FFR) in stable coronary disease is often a decision-maker for patient qualification. Taking into account the paramount position of FFR, it is crucial to acknowledge and reduce all potential bias. AIMS: In the present study, we quantified the influence of elevated HR on FFR results using a preclinical model and then validated the results in a clinical setting. METHODS AND RESULTS: The relationship between FFR and HR was first explored experimentally in a porcine model. A clinical validation study was conducted in patients with isolated moderate lesions in the left anterior descending artery (LAD) or right coronary artery (RCA). In both the experimental and clinical arms, FFR was measured at resting HR and with pacing at 100, 130, 160, and 180 (for pigs) beats per minute. In the porcine model and in the clinical settings, a significant correlation between FFR and HR was confirmed in the LAD (r = 0.89, p < .0001; r = 0.53, p = .00002), but not in the RCA (r = -0.19, p = .5; r = 0.14, p = .3). Post hoc analyses revealed that the FFR values in the LAD at 130/min and above tended to be significantly different from the baseline HR. CONCLUSIONS: The results of this study indicate that in an experimental setting, tachycardia might be responsible for an overestimation of FFR results in LAD lesions.

Genetic and environmental factors associated with homocysteine concentrations in a population of healthy young adults. Analysis of the MAGNETIC study.

BACKGROUND AND AIMS: Elevated homocysteine concentration is associated with a higher risk of cardiovascular disease. The aim of our study was to determine the environmental and genetic factors associated with serum homocysteine concentration in healthy young adults. Moreover, we aimed to determine the cutoff value of homocysteine concentration for predicting unfavorable MTHFR genotype and to investigate whether this association is modified by dietary patterns and serum folate status. METHODS AND RESULTS: A total of 744 healthy individuals, aged 18-35 years, were included in the study. Diet quality was assessed by establishing diet quality scores and adherence to the pro-Healthy Diet Index (pHDI) and non-Healthy Diet Index (nHDI). Genotyping was performed using the TaqMan method. Multivariate analysis showed that pHDI, creatinine, folate concentrations, and the T/T genotype of the C677T polymorphism in MTHFR, as well as the interaction between the T/T genotype of MTHFR (C677T polymorphism) and folate level, were most strongly related to homocysteine concentrations. The specificity of a homocysteine >13.1 µmol/l in predicting T/T homozygous status was 76% (area under the curve 0.68). CONCLUSION: Healthy dietary patterns, folate, and creatinine levels, as well as the C677T polymorphism, proved to be the strongest predictors of homocysteine concentrations. T/T genotype of MTHFR modifies the relationship between folate and homocysteine.

Cardiac assessment in Wilson's disease patients based on electrocardiography and echocardiography examination.

INTRODUCTION: Wilson's disease (WD) is a rare genetic disorder that leads to impairments in copper metabolism. Patients principally exhibit liver and neuropsychiatric symptoms, but because copper also accumulates in all body organs, other (typically milder) clinical symptoms can occur. To date, cardiac involvement has not been thoroughly investigated in patients with WD. This study aimed to evaluate heart structure and function in patients with WD with commonly available diagnostic methods. MATERIAL AND METHODS: We compared 125 WD patients with an age- and sex-matched control group. Patients with WD were grouped according to their dominant symptoms - neurologic or hepatic. All subjects underwent clinical, electrocardiographic (ECG), and echocardiographic examinations. RESULTS: All subjects had sinus rhythm on electrocardiography. The only ECG parameter that differed between patients with WD and the control group was the QRS prolongation (92.0 vs. 86.4 ms; p < 0.05). On echocardiography patients with WD exhibited more hypertrophy in the left ventricle than controls (posterior wall in diastole: 1.0 vs. 0.93; p < 0.01) and the left ventricle hypertrophy was more pronounced in the neurologic than in the hepatic subgroup (1.05 vs. 0.96 cm; p < 0.01). Left ventricular systolic function was similar in the WD and the control group (ejection fraction: 67.5% vs. 67.7%). On tissue Doppler echocardiography patients with WD demonstrated slowing of myocardial relaxation, which was more evident in the neurologic group. CONCLUSIONS: Heart involvement in WD was manifested mainly by mild left ventricular hypertrophy and subclinical changes in diastolic function, particularly in the patients with the neurologic form of disease.

ST-segment elevation myocardial infarction with non-obstructive coronary arteries in a patient with severe diabetic acidosis.

Patients with severe diabetic acidosis may present varying electrocardiography (ECG) abnormalities including ST-segment elevation. The authors described a case of 70-year-old type 2 diabetic woman hospitalized due to ST elevation myocardial infarction and serious metabolic disorders. According to the clinical presentation, the ECG abnormalities and the significant rise in myocardial necrosis biomarkers the patient was diagnosed with myocardial infarction and received a typical pharmacological treatment. In the autopsy, no signs of myocardial infarction and no significant stenoses in the coronary arteries were found, while the features of acute upper gastrointestinal bleeding were observed. This case report demonstrates that together with the clinical presentation of metabolic disorders, ST elevation must always be interpreted very cautiously and each case require an individual proceeding.

Health problems in females carriers of premutation in the FMR1 gene. / Problemy zdrowotne u kobiet nosicielek premutacji w genie FMR1.

Premutation in the FMR1 gene occur in the general population with an estimated prevalence 1 in 130-260 females and 1 in 250-810 males. Carriers of premutation are at risk of development of spectrum of neurological, psychiatric and immunological disorders in adulthood. Fragile X-associated disease caused by dynamic mutation (expansion of CGG repeats) can be divided into three disorders: FXS - Fragile X syndrome, FXPOI - Fragile X-associated primary ovarian insufficiency, FXTAS -Fragile X-associated tremor/ataxia syndrome, which can be present in few generations of one family. Immuno-mediated disorders are more common in premutation carriers as compared to control group, especially hypothyroidism and fibromyalgia. Although FMR1-associated conditions are not curable, timely diagnosis through genetic testing is important as it can lead to implementation of treatment strategies and behavioral interventions considered to improve symptoms. Knowledge of expanded allele status for females helps them to make more informed reproductive decisions.

Plasma Levels of Leptin and Adiponectin in Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common form of familial mental retardation and one of the leading known causes of autism. The mutation responsible for FXS is a large expansion of the CGG repeats in the promoter region of the FMR1 gene, resulting in the transcriptional silencing of the gene. Leptin may be considered a cytokine-like hormone with pleiotropic actions since it may be involved in the regulation of neuroendocrine functions and the immune system response, in addition to playing a role in development. Leptin and adiponectin may act in parallel as opposing metabolic counterparts. The involvement of leptin and adiponectin in the pathophysiology of FXS was hypothesized. MATERIAL AND METHODS: Twenty-three male patients affected by FXS (full mutation in the FMR1 gene) and 24 controls were included in the study. Plasma leptin and adiponectin levels were measured by the ELISA method using commercially available kits. RESULTS: Adiponectin levels in FXS patients were significantly lower than those found in controls (p < 0.04). Leptin levels in FXS patients were significantly higher than those found in controls (p = 0.03). CONCLUSION: Adipokines may be involved in the psychiatric features observed in FXS patients. Further investigations are necessary to evaluate the role of adiponectin and leptin in FXS.

Low Levels of HDL in Fragile X Syndrome Patients.

Fragile X syndrome (FXS) is the most common form of familial mental retardation and one of the leading known causes of autism. The mutation responsible for FXS is a large expansion of the CGG repeats in the promoter region of the FMR1 gene resulting in the transcriptional silencing of the gene in the pathophysiology of Fragile X syndrome was hypothesized. 23 male patients affected by Fragile X syndrome (full mutation in the FMR1 gene) and 24 controls were included in the study. The serum levels of HDL-C were lower in FXS patients (p < 0.001). The serum levels triacylglycerols were higher in FXS patients (p = 0.007) Further study involving larger samples are necessary to confirm the results and define the health implications for abnormal lipid levels in FXS patients.

Anti-neuronal antibodies in patients with fragile X syndrome: is there a role of autoimmunity in its pathogenesis?

BACKGROUND: Fragile X syndrome (FXS) is a single-gene disorder with a broad spectrum of involvement, including cognitive and behavioural impairments of varying degrees with specific physical features and a strong association with autism. OBJECTIVES: In this study, the frequency of serum anti-neural antibodies was investigated in FXS patients who did and those who did not manifest autism spectrum disorders (ASD) in comparison to typically developing controls. METHODS: The study involved 23 males (mean age, 19.78 ± 6.56 years) who harboured a full mutation in the FMR1 gene. The control group comprised 19 healthy students (mean age 24.63 ± 1.89 years). Serum anti-neuronal antibodies were analyzed using Western blotting. RESULTS: Serum anti-neuronal antibodies were present in 10/23 (43.48%) FXS males. CONCLUSION: Serum anti-neuronal antibodies were found in a subgroup of FXS patients. Autistic symptoms in FXS may, in part, be caused by auto-immune factors. Further studies in larger patient and control groups are necessary to elucidate the aetiopathogenic role of anti-neuronal antibodies in FXS patients.

[Molecular aspects of autism spectrum disorders]. / Molekularne podloze zaburzen ze spektrum autyzmu.

Autism, also known as autism spectrum disorders (ASD), is etiologically and clinically heterogeneous group ofneurodevelopmental disabilities. ASD affects 1% of child's population. The sex difference is observed with 4:1 male to female ratio. This is descriptive diagnosis based on observation and analysis of behavior and cognitive functions. ASD does not fit the criteria of known patterns of inheritance. For the majority of patients polygenic model of inheritance with many interacting genes is the most probable. The etiology ofASD is poorly understood. It is estimated that a specific genetic etiology can be determined in up to 20% of individuals with ASD. Advances in microarray technology and next generation sequencing are revealing copy variant numbers (CNV) and single nucleotides polymorphisms (SNP) with important roles in synapse formation and function. For families where a specific etiology has been identified, the risk of recurrence in siblings generally depends on the etiologic diagnosis. For autism of unknown cause, the sibling risk varies across studies but is generally considered to range from 5 to 10%.