Sudden Cardiac Death (SCD) is the leading cause of cardiovascular death in dialysis patients. This review discusses potential underlying arrhythmic mechanisms of SCD in the dialysis population. It examines recent evidence from studies using implantable loop recorders and from electrophysiological studies in experimental animal models of chronic kidney disease. The review summarizes advances in the field of non-invasive electrophysiology for risk prediction in dialysis patients focusing on the predictive value of the QRS-T angle and of the assessments of autonomic imbalance by means of heart rate variability analysis. Future research directions in non-invasive electrophysiology are identified to advance the understanding of the arrhythmic mechanisms. A suggestion is made of incorporation of non-invasive electrophysiology procedures into clinical practice. Key Concepts : – Large prospective studies in dialysis patients with continuous ECG monitoring are required to clarify the underlying arrhythmic mechanisms of SCD in dialysis patients. – Obstructive sleep apnoea may be associated with brady-arrhythmias in dialysis patients. Studies are needed to elucidate the burden and impact of sleeping disorders on arrhythmic complications in dialysis patients. – The QRS-T angle has the potential to be used as a descriptor of uremic cardiomyopathy. – The QRS-T angle can be calculated from routine collected surface ECGs. Multicenter collaboration is required to establish best methodological approach and normal values. – Heart Rate Variability provides indirect assessment of cardiac modulation that may be relevant for cardiac risk prediction in dialysis patients. Short-term recordings with autonomic provocations are likely to overcome the limitations of out of hospital 24-h recordings and should be prospectively assessed.

Cardiovascular mortality is very high in chronic and end-stage kidney disease (ESKD). However, risk stratification data are lacking. Sudden cardiac deaths are among the most common cardiovascular causes of death in these populations. As a result, many studies have assessed the prognostic potential of various electrocardiographic parameters in the renal population. Recent data from studies of implantable loop recordings in haemodialysis patients from five different countries have shed light on a pre-eminent bradyarrhythmic risk of mortality. Importantly, heart block addressed by permanent pacing system was detected in a proportion of patients during the prolonged recording periods. Standard electrocardiogram is inexpensive, non-invasive and easily accessible. Hence, risk prediction models using this simple investigation tool could easily translate into clinical practice. We believe that electrocardiographic assessment is currently under-valued in renal populations. For this review, we identified studies from the preceding 10 years that assessed the use of conventional and novel electrocardiographic biomarkers as risk predictors in chronic and ESKD. The review indicates that conventional electrocardiographic markers are not reliable for risk stratification in the renal populations. Novel parameters have shown promising results in smaller studies, but further validation in larger populations is required.

Background: Cardiovascular disease is the commonest cause of death in hemodialysis (HD) patients but accurate risk prediction is lacking. The spatial QRS – T angle is a promising electrophysiological marker for sudden cardiac death risk stratification. The aim of this study was to assess the prognostic value of spatial QRS-T angle derived from standard 12 lead electrocardiograms (ECG) and its association with echocardiographic parameters in HD patients. Methods: This prospective study of 178 prevalent HD patients (aged 67 ± 14 years, 72% men) collected ECG and echocardiographic data on an annual basis. Baseline echocardiograms at study entry were used for cross-sectional comparisons with ECGs. Study endpoints were all-cause mortality, cardiovascular mortality, and major adverse cardiac events (MACE). The QRS – T angle was calculated from standard 10-s ECG as the total cosine R to T (TCRT) using singular value decomposition and expressed in degrees. TCRT above 100° was defined as abnormal. Results: During a follow-up period of 36 ± 19 months, 74 patients died, including 17 cardiac deaths, and 54 suffered from MACE. In multivariate Cox regression analysis, QRS-T angle by TCRT at baseline was associated with increased cardiovascular mortality both as a continuous value and dichotomized below or above 100° (HR 1.016, p = 0.029, CI: 1.002–1.030 and HR 3.506, CI: 1.118–10.995, p = 0.031 respectively) and with MACE dichotomized at 100° (HR 1.902, CI: 1.046–3.459; p = 0.035). In multivariate regression analysis including baseline parameters, echocardiographic global longitudinal strain (GLS) was significantly correlated with TCRT ( F 9.648, r 2 = 0.192, standardized β = 0.331, unstandardized β = 3.567, t = 4.4429, CI: 1.976–5.157, p < 0.001). Conclusion: TCRT correlates with GLS and is independently associated with cardiac deaths and MACE in HD patients.

In the intravenous iron therapy to treat iron deficiency anaemia in patients undergoing major abdominal surgery (PREVENTT) trial, the use of intravenous iron did not reduce the need for blood transfusion or reduce patient complications or length of hospital stay. As part of the trial protocol, serum was collected at randomisation and on the day of surgery. These samples were analysed in a central laboratory for markers of iron deficiency. We performed a secondary analysis to explore the potential interactions between preoperative markers of iron deficiency and intervention status on the trial outcome measures. Absolute iron deficiency was defined as ferritin <30 lg.l À1 ; functional iron deficiency as ferritin 30-100 lg.l À1 or transferrin saturation < 20%; and the remainder as non-iron deficient. Interactions were estimated using generalised linear models that included different subgroup indicators of baseline iron status. Co-primary endpoints were blood transfusion or death and number of blood transfusions, from randomisation to 30 days postoperatively. Secondary endpoints included peri-operative change in haemoglobin, postoperative complications and length of hospital stay. Most patients had iron deficiency (369/452 [82%]) at randomisation; one-third had absolute iron deficiency (144/452 [32%]) and half had functional iron deficiency (225/452 [50%]). The change in pre-operative haemoglobin with intravenous iron compared with placebo was greatest in patients with absolute iron deficiency, mean difference 8.9 g.l À1 , 95%CI 5.3-12.5; moderate in functional iron deficiency, mean difference 2.8 g.l À1 , 95%CI À0.1 to 5.7; and with little change 320

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Background and Aims Left ventricular hypertrophy is common in end stage renal disease (ESRD) and haemodialysis. Its association with cardiovascular outcomes has been demonstrated. In this study we evaluated the diagnostic accuracy of electrocardiographic methods of calculating LVH compared to Real Time 3- Dimensional Echocardiogram (RT3DE) which we used as a surrogate gold standard test. Method This study was performed as a post-hoc analysis of a sub-group of patients enrolled into the Salford Kidney Study (SKS). Patients included into this analysis are from the sub-group of SKS previously known as the CRISIS-HD cohort. All adult haemodialysis patients at Salford Royal NHS Foundation Trust, UK or one of its satellite units are considered for inclusion. In this study we examined the sensitivity, specificity, positive predictive value and negative predictive value of Sokolow – Lyon and Romhilt –Estes methods in comparison to RT3DE. Results The final sample comprised 44 patients. The vast majority were Caucasian (39 patients). The mean age of the patients was 62 ± 13 years and mean time on dialysis 5.1 ± 2.9 years. The sensitivity of both ECG methods for diagnosis of LVH was very low. This was the case for the whole sample and also for individual groups. Romhilt – Estes was marginally better than Sokolow – Lyon and that was especially the case for male patients. Conclusion Our study shows that ECG methods for assessment of LVH that rely on voltage criteria have very low sensitivity and unreliable specificity compared to RT3DE and also conventional M –Mode echocardiography. As a result, they could not be reliably used as a quick and inexpensive method of LVH estimation in clinical practice in the case of haemodialysis patients.

Background and Aims Cardiovascular disease is common in chronic and end stage kidney disease. Left ventricular hypertrophy (LVH) has been identified as contributor to cardiovascular risk in this population. The aim of the study was to assess whether the combined use of electrocardiography and echocardiography in assessing LVH in a haemodialysis population can provide improved risk stratification. Method Prospective study of 192 prevalent maintenance haemodialysis ( HD) patients 12 lead ECGs were performed on a mid week non –dialysis day. Electrocardiographic strain was defined as a down slopping convex ST segment with inverted T waves in leads V5 and / or V6. Transthoracic echocardiographic was performed immediately after ECG .LV mass was indexed to body surface area (LVMIBSA). LVH was determined if LVMI &gt;116g/m2 for male patients, and &gt;100g/m2 for female patients. The primary study endpoint was major cardiac events (MACE). A secondary endpoint was all cause mortality. Results 192 patients included in the final analysis, 137 (71.4%) male.. The mean ejection fraction (EF) was 60.6± 11.1 % and the mean LVMI (BSA) was 115.0± 36.8 g/m2. During a mean follow up period of 2.4 ± 1.0 years, 50 patients reached a MACE end point and 62 patients died. On univariate Cox regression analysis, the factors associated with MACE were the presence of ECG strain (HR 2.961, CI: 1.254 – 6.990, p= 0.013)) URR (HR 0.968, CI: 0.942 – 0.994, p=0.015) and history of CAD (HR: 2.397 CI: 1.363 -4.2515, p= 0.002). In multivariate Cox regression analysis adjusting for baseline cardiovascular phenotype and dialysis parameters ECG strain remained significantly associated with MACE. Conclusion The presence of electrocardiographic strain increases the risk for MACE independently of LVH in haemodialysis patients. ECG strain has potential to be a simple bedside prognostic biomarker and even therapeutic target in haemodialysis patients.

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