Introduction In standard practice, LV volumes and EF are estimated by 2D technique. 3D echocardiographic assessment seems more reliable; however, this method has not yet been validated in the general population. Purpose To validate 3D echocardiography in a large population sample and investigate differences between 2D and 3D LVEF and volumes Methods In The Copenhagen City Heart Study, 4466 echocardiograms were available for analysis. The echocardiograms were obtained during four consecutive heartbeats in both 2D and 3D with GE Vivid E9. Offline analysis was performed on EchoPac v. 201. LVEF was calculated by the modified Simpsons Biplane Auto EF for 2D and by the 4LVQ method for 3D. Results The study included 2090 echocardiograms. The mean 2D LVEF was 57.3 ± 6.1% (IQR 54 - 61%) and 51.7 ± 7.9% (IQR 47 - 57%) by 3D. The mean end-diastolic volume (EDV) and end-systolic volume (ESV) by 2D and 3D techniques were: EDV 2D 106.1 ± 29.6 ml vs EDV 3D 128.2 ± 32.3 ml , ESV 2D 45.7 ± 15.6 ml vs. ESV 3D 45.7 ± 20.7 , p < 0.05 among all variables. The average difference of means between 2D and 3D LVEF was 5.6 ± 11.2%, -22.1 ± 56.8 ml for EDV, and -16.9 ± 32.9 ml for ESV. The correlation coefficient for LVEF was 0.42, EDV 0.76 and for ESV 0.70. In our study, we found a significant difference in both LVEF and ventricular volumes when comparing 2D echocardiograms with 3D. 3DE had, in general, lower LVEF, higher EDV and ESV compared to 2D. Table 1: Summary of results Table 1 - Summary of results n = 2090 Variable Min Max Mean IQR (25-75) p-value LVEF, 2D (%) 18 76 57.3 ± 6.1 54-61 < 0.05 LVEF, 3d (%) 13 77 51.7 ± 7.9 47-57 < 0.05 EDV, 2D (ml) 13 275 106.1 ± 29.6 85-123.8 < 0.05 EDV, 3D (ml) 50 270 128.2 ± 32.3 106-148 < 0.05 ESV, 2D (ml) 15 150 45.7 ± 15.6 35-54 < 0.05 ESV, 3D (ml) 13 185 45.7 ± 20.7 48-74 < 0.05 LVEF: left ventricle ejection fraction, EDV: end-diastolic volume, ESV: end systolic volume, IQR: Inter-quartile range Abstract 1180 Figure 1: Correlation and BA-plot

Abstract Introduction Three-dimensional (3D) echocardiography (3DE) is currently extensively used to estimate left ventricle (LV) morphology and heart valves. However, it is underutilized in the assessment of LV function. Most likely, it is due to limited knowledge of the normal reference intervals. In order to fill this knowledge gap, studies which investigates the 3DE reference ranges in a larger cohort of a general population are needed. The objective of the current study was to study the relationship and distribution of 3D LV ejection fraction (EF) and its corresponding strain values in subjects enrolled in Copenhagen City Heart Study (CCHS). Methods The echocardiograms were acquired from CCHS subjects from 2011–2014 by using GE Vivid E9 (GE Medical, Copenhagen, Denmark), during four consecutive heart beats. Exclusion critera were missing data or measurements in 3D, poor image quality or frame rate (<12 fps) and, based on visual evaluation of the echocardiograms, inappropriate tracking of three or more myocardial segments in the strain analysis. The echocardiograms were analysed in 2019 on EchoPacTM v. 201 (GE Medical, Copenhagen, Denmark). Results are presented in means, interquartile ranges (IQR) and as adjusted correlation values (r2). R2 values equal to or above 0.64 (equals to r=0.8) were considered as strong correlation. LV function parameters included were LVEF, global longitudinal strain (GLS), global circumferential strain (GCS) and area strain (AS). LVEF and strain results are presented as percentages (%). The distribution and relationship between 3D LVEF, GLS, GCS and AS are visualized as scatter plots and box-whiskers plots. The statistical analysis and the visualisation of the data was performed in RStudio v. 3.5.1. P-values <0.005 were considered as markers for statistical significance. Results There were 2955 subject with available 3DEs in CCHS among which 1202 subjects had sufficient image quality for evaluation. The mean 3D LVEF was 54.6% (IQR: 50–60%), 3D GLS −14.5% (IQR: −13 to −16), 3D GCS −13.4% (IQR: −11 to −15) and AS −24.7% (IQR: −22 to −27). The adjusted correlation values between LVEF with strain parameters were: 0.04 (GLS), 0.37 (GCS) and 0.26 (AS), which was poor. Conclusion This study provides valuable data of the distribution of 3D LVEF and its corresponding 3D strain values in a general population. The 3D strain values are lower than the reference interval described in literature for two-dimensional echocardiography. Moreover, correlation was also found to be poor between LVEF and different strain parameters. 3D LVEF vs. 3D Strain (GLS, GCS, AS) Funding Acknowledgement Type of funding source: None

Objective: Renal failure and hemodialysis (HD) affect the anabolic growth hormone (GH)-insulin-like growth factor (IGF) axis. A positive correlation between serum IGF-I and normalized protein catabolic rate (PCRn) in HD patients has been reported, and the aim of this study was to assess the metabolic impact of recombinant human (rh)GH in these patients.Material and Methods: In a randomized, double-blind, placebo-controlled study, rhGH was given to 35 HD patients for 8 weeks: 0.025 IU/kg/day for 1 week, increasing to 0.05 IU/kg/day. Patients with diabetes, malignancy or clinical signs of infection and those receiving steroid treatment were excluded.Results: All patients completed the study. Side-effects were rare and equally distributed between the two groups. Post-treatment, serum IGF-I and IGF-I standard deviation score (IGF-I SD) increased in the rhGH group compared to the placebo group: 283+/-33 vs 151+/-16 mg/l (p=0.001) and 1.8+/-0.6 vs -0.2+/-0.6 (p=0.002), respectively. IGF binding protein-3 was higher in the rhGH group compared to the placebo group: 5859+/-285 vs 4369+/-321 mg/l (p=0.002). PCRn was significantly higher in the rhGH group compared to the placebo group: 1.09+/-0.06 vs 0.90+/-0.06 g/kg/day (p=0.029). No differences were found in body weight, serum albumin or leptin between the two groups. There was no change in C-reactive protein (CRP) in the rhGH group compared to the placebo group: 17.4+/-9.0 vs 12.3+/-4.6 mg/l (p=NS). When the patients were subgrouped according to the CRP level (< or >10 mg/l), the effect on PCRn persisted only in rhGH-treated subjects with a normal CRP level: 1.10+/-0.08 vs 0.81+/-0.09 g/kg/day (p=0.025).Conclusion: Treatment of HD patients with rhGH at a moderate dose causes augmentation of PCRn which is considered to indicate a higher dietary protein intake. The anabolic effect of rhGH seems to be abolished by subclinical inflammation.

We conducted a study of the influence of the vasoactive peptides atrial natriuretic peptide (ANP) and neuropeptide Y (NPY) on survival of patients on hemodialysis and their association and relative importance with cardiac and clinical variables. Thirty-three hemodialysis patients were characterized by age, sex, diagnosis, blood pressure, serum (S)-albumin, serum (S)-urea, hemoglobin, dialysis dose, weight gain, duration of dialysis, cardiac hypertrophy, volume, failure, and ischemia and plasma levels of ANP and NPY. The outcomes were analyzed for early deaths (<1 year) and for all deaths. The association of the variables to early deaths and all deaths, respectively, was studied in Cox proportional hazard analyses. The variables were also studied in three hierarchical steps: clinical variables only, clinical and cardiac variables, and all variables. For all deaths, the independent variables were plasma NPY (pmol/L) (hazard ratio [HR] = 1.035, p = 0.004), heart volume (ml/m2) (HR = 1.009, p = 0.001), and S-albumin (g/L) (HR = 0.750, p = 0.034). For early deaths, the independent variables were predialysis ANP (pmol/L) (HR = 1.008, p = 0.034) and NPY (pmol/L) (HR = 1.031, p = 0.026). In the hierarchical study, excluding the vasoactive peptides, heart volume, heart failure and S-albumin were independently associated with all deaths, and mean arterial blood pressure was associated with early death. When also excluding the cardiac parameters, S-albumin was associated with all deaths and mean arterial blood pressure with early death. In conclusion, plasma levels of the vasoactive peptides ANP and NPY are the most important group in a hierarchy of variables that predict imminent death in hemodialysis patients, and NPY is associated with late death. ANP and NPY apparently sum up the detrimental influence of many factors in hemodialysis patients.

Background/Aim: Malnutrition and catabolism are predominant problems in patients undergoing hemodialysis. The aim of this study was to clarify the relationship between insulin-like growth factor I (IGF-I), the serum levels of which are influenced by nutrition and which by itself promotes amino acid uptake, and insulin-like growth factor binding protein 1 (IGFBP-1), known to regulate serum (s) IGF-I and protein intake, in end-stage renal disease patients. Methods: Thirty hemodialysis patients were studied, and s-IGF-I and s-IGFBP-1 levels were measured by radioimmunoassay. The s-IGF-I method used was validated according to a reference method. The s-IGF-I standard deviation (SD) score was calculated, giving the individual deviation from the mean of a reference population. The protein intake was estimated both directly by 3-day food recall by a dietician and indirectly by normalized protein catabolic rate (PCRn). Results: The mean serum IGF-I level was 166 ± 10 μg/l, corresponding to a normal s-IGF-I SD score (0.5 ± 0.3). S-IGFBP-1 was elevated threefold to 101 ± 11 μg/l as compared with normal subjects. The s-albumin was 39.9 ± 0.5 g/l and the s-bicarbonate 24 ± 0.4 mmol/l. There were significant correlations between s-IGF-I SD score or s-IGF-I (log-transformed) and PCRn (r = 0.37, p < 0.004, and r = 0.41, p < 0.001, respectively). The s-IGF-I/s-IGFBP-1 ratio was also positively correlated with PCRn (rs = 0.36, p < 0.007, by Spearman’s rank correlation). The s-albumin was inversely correlated with log s-IGFBP-1 (r = –0.38, p < 0.01) and positively with the s-IGF-I/s-IGFBP-1 ratio (r = 0.36, p < 0.007) but not with s-IGF-I (p < 0.13). Serum total cholesterol, triglycerides, and total body fat as percentage of body weight correlated with s-IGF-I (r = 0.47, p < 0.004, r = 0.45, p < 0.01, and r = 0.42, p < 0.004, respectively) as well as with the s-IGF-I SD score. No correlations were seen between s-IGF-I and protein or caloric intake by direct estimates from dietary food recalls. Conclusions: The s-IGF-I and the s-IGF-I/s-IGFBP-1 ratio were correlated with estimates of protein intake of the patients calculated from urea kinetics (PCRn) but not with direct estimates by the dietitian. The s-IGF-I SD score and the ratio s-IGF-I/s-IGFBP-1 might be a tool to monitor anabolic status and to select hemodialysis patients for therapeutic intervention with recombinant human IGF-I and/or recombinant human growth hormone to counteract catabolism.

Hypertension often occurs with fluid overload. The most common mechanism is considered to be mediated by increased cardiac output. Hemodialysis (HD) patients frequently have large amounts of fluid overload. Neuropeptide Y (NPY) is activated by stress and contributes to hypertension and heart failure. We speculated that NPY may be released by the stress of fluid overload and, by its vasoconstrictor effect, may contribute to hypertension and heart failure. Plasma levels of NPY and other vasoconstrictors were studied in 20 HD patients with varying degrees of fluid overload, and the relationship of NPY plasma levels to blood pressure was analyzed. The plasma concentrations of NPY correlated with the degree of fluid overload (r = 0.89; P < 0.0001) and the mean arterial blood pressure (r = 0.85; P < 0.0001). Seven patients had fluid overload of greater than 6% of body weight. They had higher blood pressures and higher plasma concentrations of NPY than 13 HD patients with less than 5% of fluid retention (systolic blood pressure, 179+/-8.2 v 145+/-3.7 mm Hg, P = 0.007; NPY, 61+/-4.6 v 26.8+/-2.7 pmol/L, P < 0.001). In stepwise multiple regression analysis, NPY alone explained blood pressure elevation when analyzed with fluid overload and angiotensin II, renin, noradrenaline, and adrenaline levels. We hypothesized that fluid overload in dialysis patients is a stress- inducing state that activates the sympathetic nervous system and releases the vasoconstrictor NPY. The resulting inappropriate vasoconstriction may contribute to volume-induced hypertension and heart failure in a vicious cycle. We conclude that determination of plasma NPY levels may be useful as a marker of the clinical threat of overhydration. (Am J Kidney Dis 1998 May;31(5):803-8)

The aim of this study was to investigate the influence of hemodialysis on insulin-like growth factor-I (IGF-I) and the IGF binding proteins (IGFBPs) in patients with end-stage renal disease (ESRD). IGF-I and IGF-II circulate bound to IGFBPs which are known to influence the IGF-I bioavailability. Ten ESRD patients were studied before and after hemodialysis on low flux filters. IGF-I, insulin and IGFBP-I were measured by specific RIAs, and IGFBP-2 and IGFBP-3 were quantified by densitometry after Western ligand blotting. Diurnal curves of IGFBP-1 were performed in two additional patients. Before dialysis, the mean (+/- SEM) IGF-I level was 202.2 +/- 12.1 micrograms/l corresponding to a SD-score of 1.8 +/- 0.3. Basal IGFBP-1 was increased 2-fold compared to normal levels (82.4 +/- 24.1 micrograms/l) and increased further during hemodialysis to 118.1 +/- 28.5 micrograms/l (P < 0.007). The mean increase during dialysis in IGFBP-1 was 74 +/- 24%. Predialysis IGFBP-2 was increased to 184.8 +/- 32.5% of the reference serum and was not significantly changed by dialysis. The predialysis IGFBP-3, 38.5 kDa band was within normal levels 90.1 +/- 18.8% of the reference serum while the IGFBP-3, 41.5 kDa band was decreased to 62.4 +/- 11.3% of the reference serum. Both IGFBP-3 bands were not significantly changed after dialysis. The mean basal insulin level was high, 38.2 +/- 3.0 mU/L, in spite of normal glucose levels suggesting insulin resistance. The mean values of IGF-I, insulin and glucose were unchanged after dialysis. The ratio between IGF-I and IGFBP-1 decreased significantly after dialysis to 53% of the ratio before dialysis (P < 0.005). The ratio between IGF-I and IGFBP-2 or IGFBP-3 did not change after dialysis. The circadian variation of IGFBP-1 during dialysis days was impaired with a delayed decrease of IGFBP-1 compared to the non-dialysis day. In ESRD patients predialysis mean values of insulin, IGF-I SD-score, IGFBP-1 and IGFBP-2 were increased, while the mean densitrometric values of the IGFBP-3 bands on Western ligand blot were either normal or reduced. IGFBP-1 was raised significantly with a mean of 74% after dialysis, the predialysis level was more than 2-fold elevated with impaired circadian variation of IGFBP-1 on dialysis days. High levels of IGFBPs may bind free IGF-I and decrease IGF-I bioavailability thus contributing to the catabolism associated with dialysis.

Accurate determination of total body water in hemodialysis patients is important for calculation of the amount of fluid excess that should be removed by ultrafiltration, and for dialysis prescribing by KT/V. Indirect methods using 0.6 X body weight or pre and post serum urea concentrations are inaccurate and determination by tritiated water space requires the use of radioactivity. The authors measured the volume of distribution for antipyrine that is distributed in body water, and compared it to tritiated water space in hemodialysis patients. Sixteen patients on hemodialysis were given 500 mg antipyrine and saliva samples were collected at fixed time points. Concentrations of antipyrine in saliva were measured by high pressure liquid chromatography. Volume of distribution for antipyrine was calculated by pharmacokinetic methods. Fluid excess was determined as the difference between tritiated water space or volume of distribution for antipyrine and ideal total body water measured anthropometrically. Total body water as the volume of distribution for antipyrine was 24.8 to 61.5 (mean 44.0±10.3) L, or 68% of body weight, and tritiated water space 27.0 to 56.6 L (43.6±7.7), 67% of body weight. Volume< of distribution for antipyrine correlated weH with tritiated water space (r=0.997 and p=0.001). Fluid excess calculated from tritiated water space was between 2.5 and 12.4,(6.0+4.0) L, and from volume of distribution for antipyrine 10.7 to 13.3 (5.7±5.1) L (r=0.80,p=0.001). The authors conclude that by using a single oral dose of antipyrine, one can simply and. accurately measure total body water in hemodialysis patients.

We studied the trans compartmental speed of urea transfer by comparing concentration changes of blood urea nitrogen to mass changes of urea during 80 dialyses in six patients. The speed of urea transfer was studied as a dependent factor of 15 patient characteristics: age; gender; fluid overload; and pre and post values of and change in pulse and temperature, calcitonin gene related peptide, and mean arterial blood pressure. Concentration changes in blood urea nitrogen were measured as pre and post dialysis urea concentration, the total urea in the body was measured by pre dialysis urea and tritium total body water determinations, and the actual mass of urea removed by collecting all dialysate. As a mean, concentration of blood urea nitrogen fell 54% but the mass urea removed was only 40% for a mean ratio of 1.41. Nine factors were associated with the speed of urea transfer. Patients with fast transfer had more normal fluid balance, a normal pulse rate, body temperature, calcitonin gene related peptide values, and blood pressure both before and after dialysis. The patients with a slower transfer of urea had a lower blood pressure before and after dialysis and a more labile pulse rate and body temperature. Patients with unpredictable urea transfer were the most edematous and had the most labile blood pressure. It is important to know which patients have slow urea transfer. Such patients should not be treated by fast dialysis, and those with the slowest rates may do particularly well on continuous ambulatory peritoneal dialysis.(ABSTRACT TRUNCATED AT 250 WORDS)

To investigate the hypothesis that calcitonin gene-related peptide (CGRP), a potent vasodilator, is an important physiological defence against fluid overload, plasma CGRP concentrations were measured in various degrees of fluid overload in 26 haemodialysis patients, for whom diuresis, mediated by atrial natriuretic peptide (ANP), is not a possible defence mechanism. Plasma CGRP concentrations were positively correlated with the degree of fluid excess (r = 0·815, p = 0·0001) and were significantly higher in 5 patients with severe fluid overload than in those less severely affected (143 [SE 14] vs 52 [11] pmol/l; p<0·001). CGRP may be an effective defence against complications of fluid overload since it can increase capitance by vasodilatation.

Hypertension is an important risk factor in hemodialysis patients. Fluid overload and increased peripheral resistance are considered the two main causes. We studied the relation between volume state and blood pressure in 18 hemodialysis patients. Actual total body water (aTBW) was measured as tritium space and “ideal” total body water (iTBW) by an anthropometric method. The difference between aTBW and iTBW was considered a measure of fluid excess or deficit. Twelve patients were overhydrated, 5%-23%. Their predialysis blood pressure was significantly correlated to their degree of fluid excess; systolic BP:r=0.71, p=0.03, diastolic BP:r=0.73, p=0.02, mean arterial BP:r=0.76, p=0.03. Five of these patients had multiple antihypertensive drugs instead of adequate ultrafiltration. Five patients had a fluid deficit of -3 to -13% and hypertension due to vasoconstriction. Four of these were adequately treated with antihypertensive drugs but had exaggerated ultrafiltration. TBW determination with tritium is simple to perform and gives information on the volume state and thereby on the cause of hypertension in hemodialysis patients. Based on this, appropriate treatment can be chosen.