Dimitrios Poulikakos

Risk of sudden cardiac death in chronic kidney disease.

The review discusses the epidemiology and the possible underlying mechanisms of sudden cardiac death (SCD) in chronic kidney disease (CKD), and highlights the unmet clinical need for noninvasive risk stratification strategies in these patients. Although renal dysfunction shares common risk factors and often coexists with atherosclerotic cardiovascular disease, the presence of renal impairment increases the risk of arrhythmic complications to an extent that cannot be explained by the severity of the atherosclerotic process. Renal impairment is an independent risk factor for SCD from the early stages of CKD; the risk increases as renal function declines and reaches very high levels in patients with end‐stage renal disease on dialysis. Autonomic imbalance, uremic cardiomyopathy, and electrolyte disturbances likely play a role in increasing the arrhythmic risk and can be potential targets for treatment. Cardioverter defibrillator treatment could be offered as lifesaving treatment in selected patients, although selection strategies for this treatment mode are presently problematic in dialyzed patients. The review also examines the current experience with risk stratification tools in renal patients and suggests that noninvasive electrophysiological testing during dialysis may be of clinical value as it provides the necessary standardized environment for reproducible measurements for risk stratification purposes.

Left ventricular hypertrophy and endothelial dysfunction in chronic kidney disease

UNLABELLED Aim Mortality, predominantly due to cardiovascular events, is high in patients with chronic kidney disease (CKD) and left ventricular hypertrophy (LVH) is a strong risk factor. Vascular endothelial dysfunction (ED) is common in CKD, but its potential contribution to LVH in non-dialysis CKD is unknown. This study investigated the association of ED with LVH in non-dialysis CKD patients. METHODS AND RESULTS We studied 30 CKD patients (17 pre-dialysis and 13 renal transplant recipients) and 29 age-gender-matched controls. In both groups, high-sensitivity C-reactive protein (hsCRP) levels, systemic ED (brachial artery flow-mediated dilatation, FMD), and LVH using two-dimensional echocardiography were measured. LV mass index (LVMI) was calculated using Penn formula and indexed by height. CKD patients had higher CRP levels (3.9 ± 2.8 vs. 1.0 ± 0.7 mg/L; P < 0.001), reduced FMD (3.2 ± 2.1 vs. 6.1 ± 1.9%; P < 0.001), and increased LVMI (146.1 ± 40.2 vs. 105.3 ± 26.2 g/m; P < 0.001), compared with controls. In CKD patients, LVMI increased with decreasing FMD (r = -0.371; P = 0.043) and FMD decreased with increasing CRP (r = -0.741; P < 0.001). Patients with low FMD <2.3% had higher CRP and LVMI (161.9 ± 48.9 vs. 130.4 ± 20.7 g/m; P = 0.033), compared with CKD patients with FMD ≥2.3%. There was no significant difference in age, blood pressure, cholesterol, FMD, and LVMI between pre-dialysis and post-renal transplant CKD patients. In multivariate regression, the relationship between LVMI and FMD remained significant after adjusting for age, diabetes, and smoking (adjacent beta = -0.396; P = 0.004). CONCLUSION This pilot study demonstrates for the first time a relationship of ED with LVH in non-dialysis CKD patients; suggesting but not proving a cause-effect relationship.

Major arrhythmic events and T wave morphology descriptors in hemodialyzed patients.

BACKGROUND Sudden cardiac death is common in patients receiving regular hemodialysis (HD). We recently demonstrated that selected repolarization descriptors calculated from electrocardiographic monitoring during HD demonstrate intra-subject stability. In this study we followed up the initial cohort for major arrhythmic events (MAE). METHODS Holter electrocardiograms (ECGs) were recorded during dialysis in 81 HD patients and repeated 5 times at 2 week intervals. The QRS-to-T angle (TCRT), the principal component analysis (PCA) ratio and the T wave morphology dispersion (TMD) were calculated in overlapping 10 second ECG segments and averaged overall recordings in each patient. Patients were followed up for MAE and non-arrhythmic mortality. RESULTS During 18 ± 3 months, 3 patients experienced MAE. Compared to others, MAE patients exhibited extreme TCRT and TMD values and minimal intradialytic changes. CONCLUSION The prognostic value of repolarization descriptors from intradialytic monitoring should be assessed prospectively.

T wave morphology changes during hemodialysis

BACKGROUND Risk stratification for sudden cardiac death in hemodialysis (HD) patients is an unmet clinical need. Non invasive electrophysiological testing is challenging in these patients due to their oscillating cardiovascular and electrolyte status induced by the intermittent HD treatment. We hypothesized that continuous electrocardiographic monitoring during their regular HD session can provide reproducible repolarisation profiles. METHODS Continuous 12-lead digital electrocardiographs (ECGs) were recorded during dialysis in stable patients and were repeated at two-week intervals for 5 times. QRS-to-T angle (TCRT), principal component analysis (PCA) ratio and T wave morphology dispersion (TMD) were calculated every 5s in overlapping 10-s ECG segments. Serum electrolytes and plasma parathyroid hormone (PTH) levels were measured prior to the first recording. RESULTS There were 319 acceptable recordings from 76 hemodialysed patients. Repeated Measures Anova showed intra-subject reproducibility of all descriptors. Mean PCA ratio and TMD values increased through dialysis and their intradialytic change correlated with heart rate changes (r = 0.305, p = 0.007 and r = 0.287, p = 0.012, respectively). TCRT showed a variable response to HD and the intradialytic change correlated positively with PTH levels (r = 0.284, p = 0.023). CONCLUSION Repolarisation descriptors demonstrate subject-specific dynamic profiles during HD. PTH has a role in dynamics of myocardial repolarisation. The potential clinical utility of continuous intradialytic ECGs for risk stratification purposes should be prospectively evaluated.

Parathyroid Hormone and Heart Rate Variability in Haemodialysis Patients

Background: Depressed heart rate variability (HRV) reflects abnormal cardiac autonomic regulation and has been linked with increased cardiovascular risk and sudden cardiac death. High parathyroid hormone (PTH) levels have also been associated with an increased risk of sudden cardiac death in haemodialysis (HD) patients. Our aim was to investigate the association between HRV indices and PTH in HD patients. Methods: Continuous intradialytic electrocardiograms were repeated in stable HD patients 5 times every 2 weeks. The absolute values of high-frequency (HF) and low-frequency (LF) HRV components were calculated every 5 min and averaged during the first and last hour of each recording (distinguished by subscripts F and L, respectively). Pre-HD PTH, corrected calcium, and phosphate levels were measured before the first recording. Results: Data were analysed for 75 subjects aged 60 ± 15, 32% females, 37% diabetics. Baseline biochemical parameters were PTH 44 ± 32 pmol/l, calcium 2.3 ± 0.2 mmol/l, and phosphate 1.6 ± 0.4 mmol/l. All HRV indices showed intra-subject stability over the 5 recordings. Diabetics had lower LFL compared to non-diabetics (-5.5 ± 0.5 vs. -5.2 ± 0.5 after logarithmic transformation, p = 0.012). In non-diabetics, PTH correlated negatively with LFL and HFL (LFL r = -0.340, p = 0.020, HFL r = -0.325, p = 0.026) and phosphate correlated negatively with LFF (r = -0.427, p = 0.003), HFF (r = -0.442, p = 0.002) and HFL (r = -0.307, p = 0.040). Conclusion: High PTH and phosphate are associated with depressed HRV in non-diabetic dialysis patients. Prospective studies are needed to evaluate the role of mineral abnormalities in autonomic imbalance and arrhythmic risk in HD patients.

Low serum sodium is associated with protein energy wasting and increased interdialytic weight gain in haemodialysis patients

Background Low serum sodium (Na) has been associated with decreased body mass index and increased cardiovascular mortality in haemodialysis (HD) patients. We examined the relationship between serum Na and selected nutritional parameters of protein energy wasting that are not affected from the hydration status in a cohort of HD patients. Methods Triceps skinfold thickness (TSF), mid-arm circumference (MAC), mid-arm muscle circumference (MAMC), handgrip strength (HGS) and subjective global assessment (SGA) were assessed in maintenance HD patients using standard techniques. MAMC was calculated with the formula MAMC (cm) = MAC (cm) −3.142 × TSF cm. Pre-dialysis serum Na values from routine monthly laboratory measurements were averaged for the last 6 months prior to the nutritional assessment. Results Altogether 172 patients with anthropometric data were included in the final analysis. Mean age was 66 ± 14, females 62 (36%) and diabetics 48 (28.9%). Patients with pre-dialysis serum Na below the mean value (136.2 mEq/L) had lower MAMC, HGS, SGA scores and albumin levels (23.50 ± 3.16 cm versus 24.58 ± 3.71 cm, P = 0.048; 21.7 ± 13.6 kg versus 28.0 ± 12.4 kg, P = 0.030; 5.1 ± 1.2 versus 5.7 ± 1.0, P = 0.012 and 31.65 ± 4.73 mg/L versus 32.25 ± 3.91 mg/L, P = 0.022, respectively) and higher interdialytic weight gains. Pre-dialysis serum Na correlated positively with MAMC, handgrip and SGA (Pearsons correlation r = 0.165, P = 0.031, r = 0.237, P = 0.022 and r = 0.195, P = 0.011, respectively). Conclusion This study demonstrates that low serum sodium is associated with protein energy wasting and increased interdialytic weight gain in HD patients.

Sex-Dependent Association between Heart Rate Variability and Pulse Pressure in Haemodialysis Patients

Aims: Increased pulse pressure (PP) is associated with increased cardiovascular mortality in haemodialysis (HD) patients. Autonomic imbalance is common in HD patients and predisposes to sudden cardiac death, but its relationship to PP is unknown. We investigated the relationship between cardiac autonomic modulation assessed by heart rate variability (HRV) and PP in HD patients. Methods: Continuous electrocardiograms recorded during HD sessions were repeated 5 times at 2-week intervals in stable HD patients. The high-frequency (HF) and low-frequency (LF) components and the LF/HF ratio of HRV were calculated during the first and last hour of the recordings. These values and the corresponding systolic blood pressure (SBP), diastolic blood pressure (DBP) and PP measurements were averaged in repeated recordings of each patient. Results: Seventy-six patients were included in the final analysis (aged 61 ± 15 years, 32% females, 37% diabetics). In male patients, LF/HF correlated inversely with pre- and post-HD PP (r = -0.369, p = 0.007 and r = -0.546, p = 0.000, respectively), positively with pre- and post-HD DBP (r = 0.358, p = 0.009 and r = 0.306, p = 0.028, respectively) and inversely with post-HD SBP (r = -0.350, p = 0.011). In female patients, LF/HF correlated positively with post-HD SBP (r = 0.422, p = 0.040). Conclusion: We observed an association between PP and HRV in male HD patients. Sex differences may be important for cardiac risk assessment.