Coronary Artery Disease in Patients Undergoing Hemodialysis: A Problem that Sounds the Alarm.

Chronic kidney disease (CKD) is affecting more and more individuals over time. The importance of the increased prevalence is enhanced by the close association with the increased risk of poor individual outcomes such as death, fatal and non-fatal cardiovascular (CV) events and progression to end stage kidney disease (ESKD). ESKD requires replacement treatment such as hemodialysis (HD), a particular and complex context that unfortunately has been rarely considered in observational studies in the last few decades. The current perspective of HD as a bridge to kidney transplant requires greater attention from observational and experimental research both in the prevention and treatment of CV events in ESKD patients. We present a narrative review by performing a literature review to extrapolate the most significant articles exploring the CV risk, in particular coronary artery disease (CAD), in ESKD and evaluating possible innovative diagnostic and therapeutic tools in these patients. The risk of CAD increases linearly when the estimated glomerular filtration rate (eGFR) declines and reached the most significant level in ESKD patients. Several diagnostic techniques have been evaluated to predict CAD in ESKD such as laboratory tests (Troponin-T, N-terminal pro b-type natriuretic peptide, alkaline phosphatase), echocardiography and imaging techniques for vascular calcifications evaluation. Similarly, treatment is based on lifestyle changes, medical therapy and invasive techniques such as coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI). Unfortunately in the literature there are no clear indications of the usefulness and validity of biomarkers and possible treatments in ESKD patients. Considering the ESKD weight in terms of prevalence and costs it is necessary to implement clinical research in order to develop prognostic reliable biomarkers for CV and CAD risk prediction, in patients with ESKD. It should be highlighted that HD is a peculiar setting that offers the opportunity to implement research and facilitates patient monitoring by favoring the design of clinical trials.

Treatment strategies of the thromboembolic risk in kidney failure patients with atrial fibrillation.

The incidence and prevalence of atrial fibrillation (AF) in patients affected by kidney failure, i.e. glomerular filtration rate <15 ml/min/1.73 m2, is high and probably underestimated. Numerous uncertainties remain regarding how to prevent thromboembolic events in this population because both cardiology and nephrology guidelines do not provide clear recommendations. The efficacy and safety of oral anticoagulant therapy (OAC) in preventing thromboembolism in patients with kidney failure and AF has not been demonstrated for either vitamin K antagonists (VKAs) or direct anticoagulants (DOACs). Moreover, it remains unclear which is more effective and safer, because estimated creatinine clearance <25-30 ml/min was an exclusion criterion in the randomized controlled trials (RCTs). Three RCTs comparing DOACs and VKAs in kidney failure failed to reach the primary endpoint, as they were underpowered. The left atrial appendage is the main source of thromboembolism in the presence of AF. Left atrial appendage closure (LAAC) has recently been proposed as an alternative to OAC. RCTs comparing the efficacy and safety of LAAC versus OAC in kidney failure were terminated prematurely due to recruitment failure. A recent prospective study showed a reduction in thromboembolic events in haemodialysis patients with AF and undergoing LAAC compared with patients taking or not taking OAC. We review current treatment standards and discuss recent developments in managing the thromboembolic risk in kidney failure patients with AF. The importance of shared decision-making with the multidisciplinary team and the patient to consider individual risks and benefits of each treatment option is underlined.

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

Prognostic Impact of Percutaneous Coronary Intervention in Chronic Dialysis Patients with Acute Myocardial Infarction: Findings from the Lombardy Health Database.

Background: Patients on chronic dialysis are less likely to be treated with percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). This is due to the lack of evidence from randomized trials, concerns about possible PCI-related side effects, and multimorbidity. Therefore, routine use of PCI for treatment of dialysis patients with AMI remains an unresolved issue. Methods: We analyzed data of patients on chronic dialysis hospitalized with AMI from 2003 to 2018, by using the administrative Lombardy Health Database (Italy). Patients were grouped according to whether they underwent or not PCI during index hospitalization. The primary outcome was in-hospital mortality, 1-year mortality was the secondary endpoint. Results: During the study period, 265,048 patients were hospitalized with AMI. Of them, 3206 (1.2%) were on chronic dialysis (age 71 ± 11; 72% males). Among dialysis patients, 44% underwent PCI, while 54% underwent PCI among non-dialysis patients (p < 0.0001). Dialysis was an independent predictor of treatment with medical therapy only (OR 0.75 [95% CI 0.70-0.81]). In-hospital mortality in the dialysis cohort was 15%, significantly lower in patients treated with PCI than in those not treated with PCI (11% vs. 19%; p < 0.0001). One-year mortality was 47% and it was lower in PCI-treated patients (33% vs. 52%; p < 0.0001). The adjusted risk of the study endpoints was significantly lower in dialysis patients undergoing PCI: OR 0.62 (95% CI 0.50-0.76) for in-hospital mortality; HR 0.63 (95% CI 0.56-0.71) for 1-year mortality. Conclusions: This study showed that in AMI patients on chronic dialysis, PCI is associated with a significant in-hospital and 1-year survival benefit. Yet, they underwent PCI less frequently than patients with preserved renal function.

The conundrum of the complex relationship between acute kidney injury and cardiac arrhythmias.

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine levels, reduced urine output or both. Death may occur in 16-49% of patients admitted to an intensive care unit with severe AKI. Complex arrhythmias are a potentially serious complication in AKI patients with pre-existing or AKI-induced heart damage and myocardial dysfunction, with fluid overload, especially electrolyte and acid-base disorders, representing the pathogenetic mechanisms of arrhythmogenesis. Cardiac arrhythmias, in turn, increase the risk of poor renal outcomes, including AKI. Arrhythmic risk in AKI patients receiving kidney replacement treatment may be reduced by modifying dialysis/replacement fluid composition. The most common arrhythmia observed in AKI patients is atrial fibrillation. Severe hyperkalaemia, sometimes combined with hypocalcaemia, causes severe bradyarrhythmias in this clinical setting. Although the likelihood of life-threatening ventricular arrhythmias is reportedly low, the combination of cardiac ischaemia and specific electrolyte or acid-base abnormalities may increase this risk, particularly in AKI patients who require kidney replacement treatment. The purpose of this review is to summarize the available epidemiological, pathophysiological and prognostic evidence aiming to clarify the complex relationships between AKI and cardiac arrhythmias.

Association between lifestyle modifications and improvement of early cardiac damage in children and adolescents with excess weight and/or high blood pressure.

BACKGROUND: It is not known whether, in children and adolescents with alterations in weight and/or blood pressure (BP), lifestyle modifications are associated with an improvement of early cardiac damage. METHODS: In a pediatric population referred for excess weight, high BP, or both (n = 278, 10.6 (2.3) years), echocardiography was performed at enrollment and after 15 months of follow-up, during which participants received nonpharmacological treatment, based on correcting unhealthy lifestyles and improving dietary habits. Left ventricular mass was indexed for height (g/m2.7, LVMI), and an LVMI value higher than or equal to age- and gender-specific 95th percentile was the criterion for defining left ventricular hypertrophy (LVH). Multiple linear and logistic regression analyses were carried out to determine associations between changes in BMI and BP z-scores and changes of LVMI values and LVH prevalence, from baseline to follow-up. RESULTS: At baseline, 33.1% of study participants were hypertensive, 52.9% obese, and 36.3% had LVH. At follow-up, the prevalence of hypertension, obesity, and LVH was 18.7%, 30.2%, and 22.3%, respectively (p < 0.001 for all). A decrease in LVMI from 37.1 to 35.2 g/m2.7 (p < 0.001) was observed. Only delta BMI z-score positively related to an improvement of LVMI. Reductions of BMI (OR = 0.22, 95% CI 0.07-0.64) and diastolic BP (OR = 0.64, 95% CI 0.42-0.93) z-scores from baseline to follow-up and family history of hypertension (OR = 0.36, 95% CI 0.16-0.78) were associated with a lower prevalence of LVH. CONCLUSIONS: In a pediatric population at cardiovascular risk, changing incorrect lifestyle and dietary habits is associated with both reduction of BMI and BP values and regression of early cardiac damage. A higher resolution version of the Graphical abstract is available as Supplementary information.

Hypertension in children and adolescents.

Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given.

Relationship between endothelin and nitric oxide pathways in the onset and maintenance of hypertension in children and adolescents.

The mechanisms that regulate blood pressure are numerous and complex; one mechanism that plays an important role in this scenario is represented by the balance between the vasoconstrictor effect of endothelin-1 and the vasodilator effect of nitric oxide. While there is agreement on the fact that increased endothelin-1 activity and decreased nitric oxide bioavailability are present in hypertensive adults, the situation is less clear in children and adolescents. Not all studies agree on the finding of an increase in plasma endothelin-1 levels in hypertensive children and adolescents; in addition, the picture is often confused by the concomitant presence of obesity, a condition that stimulates the production of endothelin-1. Furthermore, there is recent evidence that, in younger obese and hypertensive subjects, there is an overproduction of nitric oxide, rather than a reduction. This condition may change over time, causing endothelial dysfunction due to a reduced availability of nitric oxide in hypertensive adolescents. The purpose of this review is to address the main biochemical and pathophysiological aspects of endothelin and nitric oxide involvement in hypertension and to summarize the available scientific evidence on their role in the onset and maintenance of high blood pressure in children and adolescents.

Sudden cardiac death in dialysis patients: different causes and management strategies.

Sudden cardiac death (SCD) represents a major cause of death in end-stage kidney disease (ESKD). The precise estimate of its incidence is difficult to establish because studies on the incidence of SCD in ESKD are often combined with those related to sudden cardiac arrest (SCA) occurring during a haemodialysis (HD) session. The aim of the European Dialysis Working Group of ERA-EDTA was to critically review the current literature examining the causes of extradialysis SCD and intradialysis SCA in ESKD patients and potential management strategies to reduce the incidence of such events. Extradialysis SCD and intradialysis SCA represent different clinical situations and should be kept distinct. Regarding the problem, numerically less relevant, of patients affected by intradialysis SCA, some modifiable risk factors have been identified, such as a low concentration of potassium and calcium in the dialysate, and some advantages linked to the presence of automated external defibrillators in dialysis units have been documented. The problem of extra-dialysis SCD is more complex. A reduced left ventricular ejection fraction associated with SCD is present only in a minority of cases occurring in HD patients. This is the proof that SCD occurring in ESKD has different characteristics compared with SCD occurring in patients with ischaemic heart disease and/or heart failure and not affected by ESKD. Recent evidence suggests that the fatal arrhythmia in this population may be due more frequently to bradyarrhythmias than to tachyarrhythmias. This fact may partly explain why several studies could not demonstrate an advantage of implantable cardioverter defibrillators in preventing SCD in ESKD patients. Electrolyte imbalances, frequently present in HD patients, could explain part of the arrhythmic phenomena, as suggested by the relationship between SCD and timing of the HD session. However, the high incidence of SCD in patients on peritoneal dialysis suggests that other risk factors due to cardiac comorbidities and uraemia per se may contribute to sudden mortality in ESKD patients.

Lipid profile assessed in the family pediatrician's office: the COLIBRI'- SIMPeF study.

There is limited information on the prevalence of dyslipidemia in the Italian pediatric population. Aim of the study was to evaluate total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglyceride levels, and associated factors in a large sample of Italian children, applying a micro-sampling procedure in the family pediatrician's office. In a population of 1910 children (50.2% males, age 7-11 years), 27.6% was overweight or obese and 28.3% had at least one parent with referred hypercholesterolemia. Total cholesterol and triglyceride levels were elevated in 4.5% and 23.5% of the subjects, respectively, while HDL cholesterol was below 40 mg/dl in 3.3%. Male gender (OR 1.58, 95% CI 1.01-2.49) and positive family history (OR 2.13, 95% CI 1.36-3.32) were independent predictors of hypercholesterolemia, while BMI z-score was associated with low HDL cholesterol (OR 1.46, 95% CI 1.13-1.88) and high levels of triglycerides (OR 1.39, 95% CI 1.26-1.55).Conclusion: The prevalence of dyslipidemia in our sample is worthy of attention. The study suggests the opportunity and feasibility to check for the presence of dyslipidemia at the family pediatrician's office. Familiarity is associated with high cholesterol levels, regardless of the children's weight class, while weight excess identifies subjects with the typical lipid profile of metabolic syndrome. What is Known: • Few data are available on the lipid profile in Italian children. • Early treatment of hypercholesterolemia is effective in reducing cardiovascular events later in life; there is no agreement on how to screen for dyslipidemia in childhood, however. What is New: • In a large sample of Italian children, familiarity doubles the risk of hypercholesterolemia, while increased BMI is associated with low HDL cholesterol levels and hypertriglyceridemia. • The pediatrician may perform an assessment of plasma lipids in his office as a first step to diagnose familial hypercholesterolemia.

Proposal for a clinical and an echocardiographic score for prediction of left atrial thrombosis in atrial fibrillation patients undergoing early electrical cardioversion.

AIMS: Left atrial thrombosis (LAT) is usually detected by transesophageal echocardiography (TEE). The aim of the present study was to identify clinical and echocardiographic factors associated with left atrial thrombosis in atrial fibrillation (AF) patients undergoing early electrical cardioversion (ECV) in order to create scores that can predict LAT, in a non-invasive way. METHODS: A consecutive cohort of patients with persistent AF scheduled for ECV was evaluated by transthoracic echocardiography and TEE. By a logistic regression model, variables significantly associated with LAT were assessed and introduced in predictive models to develop both a clinical and an echocardiographic prediction score for the presence of LAT. RESULTS: In total, 125 patients [median 71 (range 49-88) years, 60.0% males] were enrolled. Transesophageal echocardiography showed LAT in 35 patients (28%). The clinical variables significantly associated with LAT were previous stroke (OR = 4.17), higher CHA2 DS2 -VASc score (OR = 1.93), lower estimated glomerular filtration rate (OR = 0.80), and higher brain natriuretic peptide levels (OR = 1.44). Among echocardiographic parameters, E/e' ratio was directly associated with LAT (OR = 2.25), while an inverse correlation was detected with left ventricular ejection fraction (OR = 0.43) and total global left atrial strain (OR = 0.59). Two prediction scores (clinical and echocardiographic) were developed. The positive predictive values of the clinical and the echocardiographic score were 80% and 100%, respectively, while the negative predictive values were 98% and 94%, respectively. Combined use of the scores reached a positive and negative predictive value of 100%. CONCLUSIONS: When providing concordant information the two scores are able to correctly identify patients with or without LAT. An external validation is necessary to demonstrate their usefulness in the clinical practice.

Cardiovascular Risk in Children: Focus on Pathophysiological Aspects.

Cardiovascular diseases are the leading cause of death, disability, and health care costs in industrialized countries. In general, cardiovascular diseases occur in adulthood, but cardiovascular damage, including stiffening of the arteries, begins very early. Already in the first decade of life, alterations that will favor the formation of atherosclerotic plaques may be present. Cardiovascular risk factors, associated with genetic predisposition, may trigger a sequence of pathophysiological changes which are associated with the progression of the atherosclerosis process. In this frame, the role of obesity has been increasingly emphasized. Different mechanisms linking obesity to cardiovascular disease have been postulated. Endothelial dysfunction and subclinical inflammation seem to be related to the worsening of cardiovascular risk factors in obese subjects and might have an essential role in the development of insulin resistance and the initiation and progression of atherosclerotic lesions. Excess weight, and in particular visceral adiposity, are associated with hypertrophy and hyperplasia of the adipocytes, increased secretion of adipokines and inflammatory cytokines and increase in serum uric acid levels. The list of obesity-related biomarkers associated with cardiovascular damage is rapidly expanding and their importance has already been described in children as well. Pathophysiological changes involved in determining early cardiovascular damage starting from childhood are discussed in this Special Issue.

Hypocalcemia-Induced Slowing of Human Sinus Node Pacemaking.

Each heartbeat is initiated by cyclic spontaneous depolarization of cardiomyocytes in the sinus node forming the primary natural pacemaker. In patients with end-stage renal disease undergoing hemodialysis, it was recently shown that the heart rate drops to very low values before they suffer from sudden cardiac death with an unexplained high incidence. We hypothesize that the electrolyte changes commonly occurring in these patients affect sinus node beating rate and could be responsible for severe bradycardia. To test this hypothesis, we extended the Fabbri et al. computational model of human sinus node cells to account for the dynamic intracellular balance of ion concentrations. Using this model, we systematically tested the effect of altered extracellular potassium, calcium, and sodium concentrations. Although sodium changes had negligible (0.15 bpm/mM) and potassium changes mild effects (8 bpm/mM), calcium changes markedly affected the beating rate (46 bpm/mM ionized calcium without autonomic control). This pronounced bradycardic effect of hypocalcemia was mediated primarily by ICaL attenuation due to reduced driving force, particularly during late depolarization. This, in turn, caused secondary reduction of calcium concentration in the intracellular compartments and subsequent attenuation of inward INaCa and reduction of intracellular sodium. Our in silico findings are complemented and substantiated by an empirical database study comprising 22,501 pairs of blood samples and in vivo heart rate measurements in hemodialysis patients and healthy individuals. A reduction of extracellular calcium was correlated with a decrease of heartrate by 9.9 bpm/mM total serum calcium (p < 0.001) with intact autonomic control in the cross-sectional population. In conclusion, we present mechanistic in silico and empirical in vivo data supporting the so far neglected but experimentally testable and potentially important mechanism of hypocalcemia-induced bradycardia and asystole, potentially responsible for the highly increased and so far unexplained risk of sudden cardiac death in the hemodialysis patient population.

Pros and cons of antithrombotic therapy in end-stage kidney disease: a 2019 update.

Dialysis patients manifest both an increased thrombotic risk and a haemorrhagic tendency. A great number of patients with chronic kidney disease requiring dialysis have cardiovascular comorbidities (coronary artery disease, atrial fibrillation or venous thromboembolism) and different indications for treatment with antithrombotics (primary or secondary prevention). Unfortunately, few randomized controlled trials deal with antiplatelet and/or anticoagulant therapy in dialysis. Therefore cardiology and nephrology guidelines offer ambiguous recommendations and often exclude or ignore these patients. In our opinion, there is a need for an expert consensus that provides physicians with useful information to make correct decisions in different situations requiring antithrombotics. Herein the European Dialysis Working Group presents up-to-date evidence about the topic and encourages practitioners to choose among alternatives in order to limit bleeding and minimize atherothrombotic and cardioembolic risks. In the absence of clear evidence, these clinical settings and consequent therapeutic strategies will be discussed by highlighting data from observational studies for and against the use of antiplatelet and anticoagulant drugs alone or in combination. Until new studies shed light on unclear clinical situations, one should keep in mind that the objective of treatment is to minimize thrombotic risk while reducing bleeding events.

Acute effect of a peritoneal dialysis exchange on electrolyte concentration and QT interval in uraemic patients.

BACKGROUND: Hemodialysis (HD) sessions induce changes in plasma electrolytes that lead to modifications of QT interval, virtually associated with dangerous arrhythmias. It is not known whether such a phenomenon occurs even during peritoneal dialysis (PD). The aim of the study is to analyze the relationship between dialysate and plasma electrolyte modifications and QT interval during a PD exchange. METHODS: In 15 patients, two manual PD 4-h exchanges were performed, using two isotonic solutions with different calcium concentration (Ca++1.25 and Ca1.75++ mmol/L). Dialysate and plasma electrolyte concentration and QT interval (ECG Holter recording) were monitored hourly. A computational model simulating the ventricular action potential during the exchange was also performed. RESULTS: Dialysis exchange induced a significant plasma alkalizing effect (p < 0.001). Plasma K+ significantly decreased at the third hour (p < 0.05). Plasma Na+ significantly decreased (p < 0.001), while plasma Ca++ slightly increased only when using the Ca 1.75++ mmol/L solution (p < 0.01). The PD exchange did not induce modifications of clinical relevance in the QT interval, while a significant decrease in heart rate (p < 0.001) was observed. The changes in plasma K+ values were significantly inversely correlated to QT interval modifications (p < 0.001), indicating that even small decreases of K+ were consistently paralleled by small QT prolongations. These results were perfectly confirmed by the computational model. CONCLUSIONS: The PD exchange guarantees a greater cardiac electrical stability compared to the HD session and should be preferred in patients with a higher arrhythmic risk. Moreover, our study shows that ventricular repolarization is extremely sensitive to plasma K+ changes, also in normal range.

Adiponectin and Cardiovascular Risk. From Pathophysiology to Clinic: Focus on Children and Adolescents.

Adiponectin (Ad) is a cytokine produced by adipocytes that acts on specific receptors of several tissues through autocrine, paracrine, and endocrine signaling mechanisms. Ad is involved in the regulation of cell survival, cell growth, and apoptosis. Furthermore, Ad plays an important pathophysiological role in metabolic activities by acting on peripheral tissues involved in glucose and lipid metabolism such as skeletal muscle, and the liver. Adiponectin has anti-inflammatory, anti-atherogenic, and insulin-sensitizing effects. For this reason, low levels of Ad are associated with the development of cardiovascular complications of obesity in adulthood. Numerous studies have shown that, even in children and adolescents, Ad is associated with risk factors for cardiovascular diseases. In obese children, reduced levels of Ad have been reported and Ad plasma levels are inversely related with abdominal obesity. Moreover, lower Ad concentrations are associated with the development of metabolic syndrome, insulin resistance and hypertension in pediatric subjects. In addition to a higher prevalence of cardiovascular risk factors, plasma values of Ad are also inversely associated with early organ damage, such as an increase in carotid intima-media thickness. It has been suggested that low Ad levels in childhood might predict the development of atherosclerosis in adulthood, suggesting the possibility of using Ad to stratify cardiovascular risk in obese children. Some evidence suggests that lifestyle modification may increase Ad plasma levels. The aim of this review is to summarize the evidence on the relationship between Ad, obesity, metabolic alterations and hypertension in children and adolescents, and to address the possibility that Ad represents an early marker of cardiovascular risk in pediatric subjects. Furthermore, the effects of non-pharmacological treatment (weight loss and physical activity) on Ad levels are considered.

Practical issues in clinical scenarios involving CKD patients requiring antithrombotic therapy in light of the 2017 ESC guideline recommendations.

BACKGROUND: The choice of the most appropriate antithrombotic regimen that balances ischemic and bleeding risks was addressed by the August 2017 European Society of Cardiologists (ESC)/European Association for Cardio-Thoracic Surgery Focused Update recommendations, which propose new evaluation scores and protocols for patients requiring a coronary stent or patients with an acute coronary syndrome, atrial fibrillation, or a high bleeding risk and indication for oral anticoagulation therapy. DISCUSSION: Numerous questions remain regarding antithrombotic regimens and risk management algorithms for both ischemic and hemorrhagic events in patients with chronic kidney disease (CKD) in various clinical scenarios. Limitations of current studies include a general ack of advanced CKD patients in major randomized controlled trials, of evidence on algorithm implementation, and of robust assessment tools for hemorrhagic risk. Herein, we aim to analyze the ESC Update recommendations and the newly implemented risk scores (DAPT, PRECISE-DAPT, PARIS) from the point of view of CKD, providing suggestions on drug choice (which combination has the best evidence), dosage, and duration (the same or different as for non-CKD population) of antithrombotics, as well as to identify current shortcomings and to envision directions of future research. CONCLUSION: We provide an evidence-based perspective on the new proposed bleeding management protocol, with focus on the CKD population. Despite previous important steps on antithrombotic therapy of renal patients, there remain many unsolved questions for which our suggestions could fundament new randomized controlled trials and specific protocols.

Bleeding in advanced CKD patients on antithrombotic medication - A critical appraisal.

Patients with advanced chronic kidney disease (CKD) are at an increased risk of bleeding, especially in the context of the complex therapeutic schemes of coronary artery disease (CAD) (from stable angina to acute coronary syndromes), atrial fibrillation or venous thromboembolism. The bleeding issue increases morbidity and mortality, a serious problem in daily medical practice. However, these patients are largely excluded from major randomized clinical trials, which results in the lack of medical evidence-based foundation for specific recommendations regarding antithrombotic treatment in a high bleeding risk setting. Within this framework, the clinician does not benefit from a clear set of algorithms and measures in the exploration and balancing of bleeding and thrombosis risks. We discuss a diversity of scenarios, encompassing all categories of advanced CKD patients with CAD or/and atrial fibrillation, and with various combinations of drugs, such as antiplatelet therapy or/and oral anticoagulation. Our review highlights the most recent research as well as existing gaps in the recommendations of European Society of Cardiology Guidelines. We evaluate the existence or lack of assessment tools for the bleeding risk, strength, reliability and usefulness of the bleeding risk scores. Also, we identify all the measures recommended after risk evaluation, including specific plans, dose adjustments and particular therapeutic approaches. Finally, we provide with suggestions for improving the management of this patient population.

How Accurate Is a Single Cutpoint to Identify High Blood Pressure in Adolescents?

In 2007 the International Diabetes Federation (IDF) proposed single blood pressure (BP) cutpoints (systolic: ≥130 mm Hg and diastolic: ≥85 mm Hg) for the diagnosis of high blood pressure (HBP) in adolescents. Before this proposal, HBP had been defined as BP at or above the 95th percentile for age, sex, and height percentile (reference standard). In this study, we evaluated the risk for misclassification when using the IDF single-cutpoints criteria. We first applied the IDF criteria to a reconstructed population with the same age, sex, and height distribution as the population used to develop the reference standard. The proposed single cutpoints corresponded to percentiles from the 81.6th to 99.9th for systolic BP and from the 92.9th to 98.9th for diastolic BP in the reconstructed population. Using IDF criteria, there were high false-negative fractions for both systolic and diastolic BP (from 54% to 93%) in 10- to 12-year-olds and a false-positive fraction up to 35% in older subjects. We then applied the IDF criteria to 1,162 overweight/obese adolescents recruited during 1998-2000 from pediatric clinical centers in Milano, Varese, and Modena in Italy and in Zaragoza, Spain. Overall false-negative and false-positive fractions were 22% and 2%, respectively; negative predictive values were especially low for 10- to 12-year-old subjects. The use of IDF's single cutpoints carries a high risk of misclassification, mostly due to false negatives in younger subjects. The effort to simplify diagnosis could be overcome by the risk of undiagnosed HBP.

The quest for equilibrium: exploring the thin red line between bleeding and ischaemic risks in the management of acute coronary syndromes in chronic kidney disease patients.

Coronary artery disease and acute coronary syndrome (ACS) are both common in patients with chronic kidney disease (CKD). CKD patients have higher risks of bleeding and thrombosis. However, they remain under-represented in major randomized clinical trials (RCTs), and there is no medical evidence-based foundation on which to issue specific recommendations about the management of ACS in CKD. CKD patients with ACS frequently are diagnosed later, receive fewer acute interventions and are at increased risk of over-dosage of medications and under-prescription/under-performance of interventional treatments than CKD patients without ACS. The lack of RCTs should not discourage reliance on clinical common sense, while clearer decisional algorithms with better outcomes are a priority for urgent development. Future guidelines should further refine the assessment of CKD with ACS while placing much greater emphasis on the correct dosing of medications based on contemporaneous renal function. Until a strategy is designed with specific measures translated into the actual decrease of bleeding risk, providers will be forced to balance the equilibrium on a thin red line that is not clearly established.