Prediction of future cardiovascular events by Framingham, SCORE and asCVD risk scores is less accurate in HIV-positive individuals from the HIV-HEART Study compared with the general population.

OBJECTIVES: Cardiovascular diseases (CVDs) occur more often in people living with HIV (PLWH) than in the general population. It has been reported that CVD risk scores developed for the general population underestimate the CVD risk in PLWH. Performances of the Framingham Risk Score (FRS), the Systematic Coronary Risk Evaluation (SCORE) and the atherosclerotic cardiovascular disease (asCVD) risk score in PLWH were compared with the general population to quantify score-specific differences in risk prediction. METHODS: HIV-positive outpatients from the HIV-HEART (HIVH) study (n = 567) were compared with participants from the population-based Heinz Nixdorf Recall (HNR) study (n ~ 4440) both recruited from the German Ruhr area. During a follow-up time of around 5 years, the associations between the FRS and incident CVD and peripheral artery disease (CVD_pAD), SCORE and coronary heart disease (CHD), and asCVD and incident CVD were examined using logistic regression. Score performances were assessed by comparing the areas under the curve (AUCs). RESULTS: The mean ages were 52.9 ± 6.7 and 59.1 ± 7.7 years in the HIVH and HNR studies, respectively. There were fewer incident CVD events in the HNR study than in the HIVH study (CVD_pAD: 3.9% vs. 12.1%; CHD: 2.1% vs. 7.8%; CVD: 3.5% vs. 9.9%). Age- and sex-adjusted CVD risk was greater with increasing FRS, SCORE and asCVD in both cohorts, but the scores performed more accurately in the HNR than in HIVH study (AUCs FRS: 0.71 vs. 0.65; SCORE: 0.70 vs. 0.62; asCVD: 0.74 vs. 0.62). CONCLUSIONS: Associations between risk scores and future CVD were observed in both cohorts, but the score performances were less reliable in PLWH than in the general population.

Genomic additive and dominance variance of milk performance traits.

Milk performance traits are likely influenced by both additive and non-additive (e.g. dominance) genetic effects. Genetic variation can be partitioned using genomic information. The objective of this study was to estimate genetic variance components of production and milk component traits (e.g. acetone, fatty acids), which are particularly important for milk processing or which can provide information on the health status of cows. A genomic relationship approach was applied to phenotypic and genetic information of 1295 Holstein cows for estimating additive genetic and dominance variance components. Most of the 17 investigated traits were mainly affected by additive genetic effects, but protein content and casein content also showed a significant contribution of dominance. The ratio of dominance to additive variance was estimated as 0.64 for protein content and 0.56 for casein content. This ratio was highest for SCS (1.36) although dominance was not significant. Dominance effects were negligible in other moderately heritable milk traits.

Angiopoietin-2 (ANGPT2) as a candidate gene for somatic cell score in German Holstein cattle.

This study evaluated the bovine angiopoietin-2 (ANGPT2) gene as a functional and positional candidate gene underlying a previously fine mapped quantitative trait locus (QTL) for somatic cell score on bovine chromosome 27. The gene product angiopoietin-2 is directly involved in the extravasation of neutrophils, making it a promising candidate to control the amount of somatic cells in milk. A total of 11 polymorphisms were identified within the gene by comparatively resequencing the entire open reading frame of the gene as well as adjacent intronic regions. Four selected variants were genotyped in the same granddaughter design used for QTL mapping and an association study was carried out applying 2 complementary approaches. A variable number of tandem repeats in intron 7 of the gene was found to be significantly associated with cell score in all approaches and explains approximately half of the QTL variance. Analysis of ANGPT2 mRNA expression in different localizations of the udder in animals putatively carrying divergent QTL alleles revealed differential expression in the udder lymph node. Together with the physiological role of angiopoietin-2, these results support a role of ANGPT2 in the genetic control of somatic cell score. Further studies are, however, needed to further underpin this hypothesis.

Milk metabolites and their genetic variability.

The composition of milk is crucial to evaluate milk performance and quality measures. Milk components partly contribute to breeding scores, and they can be assessed to judge metabolic and energy status of the cow as well as to serve as predictive markers for diseases. In addition to the milk composition measures (e.g., fat, protein, lactose) traditionally recorded during milk performance test via infrared spectroscopy, novel techniques, such as gas chromatography-mass spectrometry, allow for a further analysis of milk into its metabolic components. Gas chromatography-mass spectrometry is suitable for measuring several hundred metabolites with high throughput, and thus it is applicable to study sources of genetic and nongenetic variation of milk metabolites in dairy cows. Heritability and mode of inheritance of metabolite measurements were studied in a linear mixed model approach including expected (pedigree) and realized (genomic) relationship between animals. The genetic variability of 190 milk metabolite intensities was analyzed from 1,295 cows held on 18 farms in Mecklenburg-Western Pomerania, Germany. Besides extensive pedigree information, genotypic data comprising 37,180 single nucleotide polymorphism markers were available. Goodness of fit and significance of genetic variance components based on likelihood ratio tests were investigated with a full model, including marker- and pedigree-based genetic effects. Broad-sense heritability varied from zero to 0.699, with a median of 0.125. Significant additive genetic variance was observed for highly heritable metabolites, but dominance variance was not significantly present. As some metabolites are particularly favorable for human nutrition, for instance, future research should address the identification of locus-specific genetic effects and investigate metabolites as the molecular basis of traditional milk performance test traits.

Investigating associations between milk metabolite profiles and milk traits of Holstein cows.

In the field of dairy cattle research, it is of great interest to improve the detection and prevention of diseases (e.g., mastitis and ketosis) and monitor specific traits related to the state of health and management. During the standard milk performance test, traditional milk traits are monitored, and quality and quantity are screened. In addition to the standard test, it is also now possible to analyze milk metabolites in a high-throughput manner and to consider them in connection with milk traits to identify functionally important metabolites that can also serve as biomarker candidates. We present a study in which 190 milk metabolites and 14 milk traits of 1,305 Holstein cows on 18 commercial farms were investigated to characterize interrelations of milk metabolites between each other, to milk traits from the milk standard performance test, and to influencing factors such as farm and sire effect (half-sib structure). The effect of influencing factors (e.g., farm) varied among metabolites and traditional milk traits. The investigations of associations between metabolites and milk traits revealed groups of metabolites that show, for example, positive correlations to protein and casein, and negative correlations to lactose and pH. On the other hand, groups of metabolites jointly associated with the investigated milk traits can be identified and functionally discussed. To enable a multivariate investigation, 2 machine learning methods were applied to detect important metabolites that are highly correlated with the investigated traditional milk traits. For somatic cell score, uracil, lactic acid, and 9 other important metabolites were detected. Lactic acid has already been proposed as a biomarker candidate for mastitis in the recent literature. In conclusion, we found sets of metabolites eligible to predict milk traits, enabling the analysis of milk traits from a metabolic perspective and discussion of the possible functional background for some of the detected associations.

Relationship between milk urea content and important milk traits in Holstein cattle.

Breeding cattle with low nitrogen emissions has been proposed as a countermeasure against eutrophication due to dairy production. Milk urea content (MU) could potentially serve as a new readily measured indicator trait for nitrogen emissions by cows. Therefore, we estimated genetic parameters related to MU and its relationship with other milk traits. We analysed 4 178 735 milk samples collected between January 2008 and June 2019 from 261 866 German Holstein dairy cows during their first, second, and third lactations. Restricted maximum likelihood estimation was conducted using univariate and bivariate random regression sire models in WOMBAT. We obtained moderate average daily heritability estimates for the daily MU of 0.24 in first lactation cows, 0.23 in second lactation cows, and 0.21 in third lactation cows with average daily genetic SDs of 25.16 mg/kg, 24.93 mg/kg, and 23.75 mg/kg, respectively. Averaged over days in milk, the repeatability estimates were low at 0.41 in first, second, and third lactation cows. A strong positive genetic correlation was found between MU and milk urea yield (MUY; 0.72 on average). In addition, 305-day heritabilities were estimated as 0.50, 0.52, and 0.50 in first, second, and third lactation cows, respectively, with genetic correlations of 0.94 or higher for MU in different lactations. By contrast, the averaged estimates of the genetic correlations between MU and other milk traits were low (-0.07 to 0.15). Moderate heritability estimates clearly allow the possible selection for MU, and the near-zero estimates of genetic correlations indicate no risk of undesired correlated selection responses in other milk traits. However, a relationship still needs to be established between MU as an indicator trait and the target trait, defined as total individual nitrogen emissions.

Optimum multistage genomic selection in dairy cattle.

The availability of different single nucleotide polymorphism (SNP) chips and the development of imputation algorithms allow for multistage dairy cattle breeding schemes applying various genomic selection strategies. These SNP genotypes yield genomically estimated breeding values (GEBV) with different accuracies at different costs. Thus, the optimum allocation of investments to different selection paths and strategies to maximize the genetic gain per year (ΔG(a)) and its sensitivity to changes in cost and accuracies of GEBV is of great interest. This is even more relevant under the constraints of limited financial resources. With deterministic methods, optimum multistage breeding plans maximizing ΔG(a) were identified in which selection could take place on GEBV derived from high-density (GEBV(HD)) and low-density (GEBV(LD)) SNP genotypes. To account for the uncertainty of cost and accuracies of GEBV, these parameters were varied in a semi-continuous manner. Overall breeding costs were limited to the crucial expenses of a traditional breeding program with 50 progeny-tested young bulls per year. Results clearly show that, in an optimal selection strategy, selection on GEBV(LD) is predominantly used for the identification of future bull dams but the main part of ΔG(a) is still generated from selection of sires. The low selection intensity in the path dam to sire induced a higher sensitivity of ΔG(a) to changes in cost and accuracies of GEBV(LD) compared with the same changes of GEBV(HD). On the contrary, the genetic gain generated from selection of males was only affected by changes in accuracies of GEBV(HD) but almost unaffected by any changes in cost. Thus, changes in cost and accuracies of GEBV(LD) put the most pressure on the breeding scheme structure to maintain a high ΔG(a). Furthermore, genomic selection of bull dams produced by far the majority of breeding cost but the lowest genetic gain.

Calculation of identity-by-descent probabilities of short chromosome segments.

For some purposes, identity-by-descent (IBD) probabilities for entire chromosome segments are required. Making use of pedigree information, length of the segment and the assumption of no crossing-over, a generalization of a previously published graph theory oriented algorithm accounting for nonzero IBD of common ancestors is given, which can be viewed as method of path coefficients for entire chromosome segments. Furthermore, rules for setting up a gametic version of a segmental IBD matrix are presented. Results from the generalized graph theory oriented method, the gametic segmental IBD matrix and the segmental IBD matrix for individuals are identical.

Pericardial effusion of HIV-infected patients ? Results of a prospective multicenter cohort study in the era of antiretroviral therapy.

BACKGROUND: Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular diseases. Previous publications described pericardial effusion as one of the most common HIV-associated cardiac affiliations. The aim of the current study was to investigate if pericardial effusion still has a relevant meaning of HIV-infected patients in the era of antiretroviral therapy. METHODS: The HIV-HEART (HIV-infection and HEART disease) study is a cardiology driven, prospective and multicenter cohort study. Outpatients with a known HIV-infection were recruited during a 20-month period in a consecutive manner from September 2004 to May 2006. The study comprehend classic parameters of HIV-infection, comprising CD4-cell count (cluster of differentiation) and virus load, as well as non-invasive tests of cardiac diseases, including a thorough transthoracic echocardiography. RESULTS: 802 HIV-infected patients (female: 16.6%) with a mean age of 44.2 ± 10.3 years, were included. Duration of HIV-infection since initial diagnosis was 7.6 ± 5.8 years. Of all participants, 85.2% received antiretroviral therapy. Virus load was detectable in 34.4% and CD4 - cell count was in 12.4% less than 200 cells/µl. Pericardial effusions were present in only two patients of the analysed population. None of the participants had signs of a relevant cardiovascular impairment by pericardial effusion. CONCLUSIONS: Our results demonstrate that the era of antiretroviral therapy goes along with low rates of pericardial effusions in HIV-infected outpatients. Our findings are in contrast to the results of publications, performed before the common use of antiretroviral therapy.

[Coronary artery disease in HIV-infected subjects. Results of 101 coronary angiographies]. / Koronare Herzerkrankung bei HIV-infizierten Personen. Ergebnisse von 101 Koronarangiographien.

BACKGROUND: The introduction of antiretroviral therapy has brought cardiac disease as a comorbidity in HIV-infected patients in particular into focus. The present study analyses the results of coronary angiography in this patient population. METHODS: Over a time period of 12 years, 101 coronary angiographies were performed in HIV-infected patients. A retrospective analysis included demographic parameters, cardiac history, cardiovascular risk factors, HIV-specific parameters including antiretroviral therapy and the results of coronary angiographies. RESULTS: Of the subjects included in the study, 89% were men. The mean age in the analysed population was 50.2 years at the time of coronary angiography. Patients had an elevated rate of cardiovascular risk factors including diabetes mellitus (15.9%), arterial hypertension (65.9%), hyperlipidemia (56.8 %) and smoking (68.2 %). Primary coronary angiography demonstrated coronary disease in 59.1%. Of all patients with coronary artery disease, 70% underwent coronary intervention. Subjects who underwent coronary intervention exhibited hyperlipidemia significantly more often (77.8% vs. 42.3%, p=0.02). Cardiovascular risk factors play a prominent role in the development of premature arteriosclerosis in HIV-infected patients. Furthermore, our data highlight the importance of invasive diagnostics in this patient group.

[Home monitoring of an incessant VT in an ICD patient]. / Monitoring eines elektrischen Sturms bei einem Patienten mit telemedizinischer ICD-Überwachung.

Due to the increasing number of patients and complexity of modern tachycardia devices, efficient therapy monitoring as offered by telemedicine monitoring is of increasing importance. The potential advantages of remote control for patient management include early detection of device-related technical problems and arrhythmias. We report the case of an ICD patient with incessant ventricular tachycardia in whom immediate arrhythmia transmission was monitored by remote control.

Analysis of birth weight variability in pigs with respect to liveborn and total born offspring.

Reduction in the variability of piglet birth weight within litter and increased piglet survival are key objective in schemes aiming to improve sow prolificacy. In previous studies, variation in birth weight was described by the sample standard deviation of birth weights within one litter, and the genetic impact has been proved. In this study, we additionally considered the sex effect on piglet's birth weight and on its variability. The sample variance of birth weights per litter separated by sex was assigned as a trait of the sow. Different transformations of the trait were fitted by linear and generalized linear mixed models. Based on 1111 litters from Landrace sows, the estimates of heritability for the different measures ranged from 11 to 12%. We analysed the influence of including birth weight of stillborn piglets on the variability of birth weight within litter. With omitted stillborns, the heritability was estimated approximately 2% higher than that in investigations of all born piglets, and the impact of sex on birth weight variability was increased. Because the proportion of intrapartum deaths is rather high, it is recommended to consider the total number of piglets born per litter when analysing birth weight variation.

Modeling heat stress effects on dairy cattle milk production in a tropical environment using test-day records and random regression models.

In tropical environments, dairy cattle production is constrained by several factors, including climate. The seasonal loss of milk due to heat stress is a recurring challenge for many dairy producers. The objective of this study was to detect heat stress thresholds, milk yield loss and individual animal variations using random regression models for dairy cattle from test-day milk records. Data were obtained from the Kenya Livestock Breeders Organization for the years 2000-2017 and merged with weather data. The weather parameters were grid-interpolated solar and meteorological data obtained from the National Aeronautics and Space Administration/Prediction Of Worldwide Energy Resources (NASA/POWER). After editing, the records comprised 49 993, 45 251 and 36 136 test-day records for first, second, and third lactations, respectively, for the four main dairy breeds: Friesian (68.0%), Ayrshire (21.1%), Jersey (7.6%) and Guernsey (3.3%). Variance components were estimated using Restricted Maximum Likelihood in ASReml software. Random regression models with third-order Legendre polynomials were fitted to the average and individual lactation curves and the reaction norms. An extended factor analytic variance structure for the random cow effects was used to estimate (co)variances between days in milk and thermal load. The daily average temperature (TA) and temperature humidity index (THI) were identified as the most suitable thermal load indicators for assessing milk yield losses. Considering a one day lag, the estimated heat stress thresholds were about 22 °C and 69 index units for TA and THI, respectively. Almost no differences were observed for estimated residual variances between the thermal load indicators, indicating there was no better model fit by TA or THI. The heat stress thresholds and milk loss patterns are important for management of dairy production systems in the tropics with climatic conditions similar to this study. Data recording should be improved as a tool to monitor the expected impacts of climate change and mitigation measures.

Quantitative trait loci mapping of calving and conformation traits on Bos taurus autosome 18 in the German Holstein population.

Linkage, linkage disequilibrium, and combined linkage and linkage disequilibrium analyses were performed to map quantitative trait loci (QTL) affecting calving and conformation traits on Bos taurus autosome 18 (BTA18) in the German Holstein population. Six paternal half-sib families consisting of a total of 1,054 animals were genotyped on 28 genetic markers in the telomeric region on BTA18 spanning approximately 30 Mb. Calving traits, body type traits, and udder type traits were investigated. Using univariately estimated breeding values, maternal and direct effects on calving ease and stillbirth were analyzed separately for first- and further-parity calvings. The QTL initially identified by separate linkage and linkage disequilibrium analyses could be confirmed by a combined linkage and linkage disequilibrium analysis for udder composite index, udder depth, fore udder attachment, front teat placement, body depth, rump angle, and direct effects on calving ease and stillbirth. Concurrence of QTL peaks and a similar shape of restricted log-likelihood ratio profiles were observed between udder type traits and for body depth and calving traits, respectively. Association analyses were performed for markers flanking the most likely QTL positions by applying a mixed model including a fixed allele effect of the maternally inherited allele and a random polygenic effect. Results indicated that microsatellite marker DIK4234 (located at 53.3 Mb) is associated with maternal effects on stillbirth, direct effects on calving ease, and body depth. A comparison of effects for maternally inherited DIK4234 alleles indicated a favorable, positive correlation of maternal and direct effects on calving. Additionally, the association of maternally inherited DIK4234 marker alleles with body depth implied that conformation traits might provide the functional background of the QTL for calving traits. For udder type traits, the strong coincidence of QTL peaks and the position of the QTL in a region previously reported to harbor QTL for somatic cell score indicated that effects of QTL for udder type traits might be correlated with effects of QTL for udder health traits on BTA18. Our results suggest that loci in the middle to telomeric region on BTA18 with effect on conformation traits may also contribute to the genetic variance of calving and udder health traits. Further analyses are required to identify the causal mutations affecting conformation and calving traits and to investigate the correlation of effects for loci associated with conformation, calving, and udder health traits.

Gametic gene flow method accounts for genomic imprinting.

Findings within the last 15 years emphasize the possible role of genomic imprinting for trait expression in livestock species. In genetic evaluation, genomically imprinted traits can be treated by models with two different breeding values per animal; one accounts for the paternal and the other for the maternal expression pattern. Relative weighting factors for these breeding values were derived by a generalized version of the discounted gene flow method, which was extended to a gametic level to account for parent-of-origin effects. The gametic approach proved also useful for calculating the expected increase in inbreeding induced by one round of selection and its dynamics over time. The gametic gene flow method was applied to a hypothetical pig breeding programme. Relative weighting factors were higher for the paternally inherited genetic effect even in female selection paths, but depend on the breeding scheme heavily. The maximum medium-term increase in inbreeding due to selection exceeded the long-term increase in a range of 20-100%.

Refined mapping of quantitative trait loci for somatic cell score on BTA02 in the German Holstein.

The aim of this study was to more precisely map a previously reported quantitative trait locus (QTL) affecting somatic cell score on Bos taurus autosome 2 by increasing the number of markers fourfold, analysing more families and exploiting within-population linkage disequilibrium (LD). A granddaughter design of 10 German Holstein grandsire families with 1121 progeny tested sons was used. Twenty-six markers with an average marker spacing of 3.14 cM were genotyped along 81.6 cM. Linkage analysis (LA) was performed using variance-component methodology. The incorporation of LD was first done using variance-component methods followed by regression on marker alleles. LA revealed genome-wide significance (LOD > 3) at 15 contiguous marker-intervals, with the maximum test-statistic between DIK2862 and BMS778 and a 1-lod drop-off interval of 38 cM. While the variance-component methods could not detect any LD, two individual markers with a significant effect (ILSTS098, p < 0.05; BMS778, p < 0.01) were found by regression analysis. Compared with previous results QTL-localisation was substantially narrowed; further fine-mapping should focus on the close vicinity of BMS778.

A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle.

A high proportion of purebred Hampshire pigs carries the dominant RN- mutation, which causes high glycogen content in skeletal muscle. The mutation has beneficial effects on meat content but detrimental effects on processing yield. Here, it is shown that the mutation is a nonconservative substitution (R200Q) in the PRKAG3 gene, which encodes a muscle-specific isoform of the regulatory gamma subunit of adenosine monophosphate-activated protein kinase (AMPK). Loss-of-function mutations in the homologous gene in yeast (SNF4) cause defects in glucose metabolism, including glycogen storage. Further analysis of the PRKAG3 signaling pathway may provide insights into muscle physiology as well as the pathogenesis of noninsulin-dependent diabetes mellitus in humans, a metabolic disorder associated with impaired glycogen synthesis.

Association between single nucleotide polymorphisms in the CXCR1 gene and somatic cell score in Holstein dairy cattle.

In addition to its position in a quantitative trait locus for somatic cell score (SCS) and its function in the immune response, the CXCR1 chemokine receptor gene located on Bos taurus autosome 2 is an auspicious candidate gene for udder health in dairy cattle. An association analysis was conducted in the German Holstein-Friesian population to test the association between the single nucleotide polymorphism (SNP) at position +777 within the CXCR1 gene and the SNP at position -1768 in the 5' upstream region of this gene (rs41255711) and the indicator trait SCS by using a grand-daughter design. Data were analyzed for 3 families, with a total of 749 genotyped bulls and an extended pedigree of 8,071 animals from the national German bovine genome mapping project. Variance component estimation was used to determine the source of phenotypic variation in the chromosomal area of interest. A 20-cM window surrounding the 2 SNP in the CXCR1 gene was examined. Although the percentage of variance caused by the putative quantitative trait locus in the area studied was relatively large (12 and 11%, respectively), no statistically significant association of the SNP CXCR1+777 or CXCR1-1768 with SCS was found. These results contradict previously published studies.

Refined positioning of a quantitative trait locus affecting somatic cell score on chromosome 18 in the German Holstein using linkage disequilibrium.

Combined linkage and linkage disequilibrium analysis (LALD) was conducted to more accurately map a previously reported quantitative trait locus (QTL) affecting somatic cell score on bovine chromosome 18. A grand-daughter design consisting of 6 German Holstein grandsire families with 1,054 progeny-tested genotyped sons was used in this study. Twenty microsatellite markers, 5 single nucleotide polymorphisms, and an erythrocyte antigen marker with an average marker spacing of 1.95 cM were analyzed along a chromosomal segment of 50.80 cM. Variance components were estimated and restricted maximum likelihood test statistics were calculated at the midpoint of each marker interval. The test statistics calculated in single-QTL linkage analysis exceeded the genome-wide significance threshold at several putative QTL positions. Using LALD, we were successful in assigning a genome-wide significant QTL to a confidence interval of 10.8 cM between the markers ILSTS002 and BMS833. The QTL in this marker interval was estimated to be responsible for between 5.89 and 13.86% of the genetic variation in somatic cell score. In contrast to the single-QTL linkage analysis model, LALD analyses with a 2-QTL model confirmed the position of one QTL, but gave no conclusive evidence for the existence or position of a second QTL. Ultimately, the QTL position was narrowed down considerably compared with previous results with a refined confidence interval of less than 11 cM.

Reliability of a novel intracardiac electrogram method for AV And VV delay optimization and comparability to echocardiography procedure for determining optimal conduction delays in CRT patients.

BACKGROUND: Echocardiography is widely used to optimize CRT programming. A novel intracardiac electrogram method (IEGM) was recently developed as an automated programmer-based method, designed to calculate optimal atrioventricular (AV) and interventricular (VV) delays and provide optimized delay values as an alternative to standard echocardiographic assessment. OBJECTIVE: This study was aimed at determining the reliability of this new method. Furthermore the comparability of IEGM to existing echocardiographic parameters for determining optimal conduction delays was verified. METHODS: Eleven patients (age 62.9+/- 8.7; 81% male; 73% ischemic), previously implanted with a cardiac resynchronisation therapy defibrillator (CRT-D) underwent both echocardiographic and IEGM-based delay optimization. RESULTS: Applying the IEGM method, concordance of three consecutively performed measurements was found in 3 (27%) patients for AV delay and in 5 (45%) patients for VV delay. Intra-individual variation between three measurements as assessed by the IEGM technique was up to 20 ms (AV: n=6; VV: n=4). E-wave, diastolic filling time and septal-to-lateral wall motion delay emerged as significantly different between the echo and IEGM optimization techniques (p < 0.05). The final AV delay setting was significantly different between both methods (echo: 126.4 +/- 29.4 ms, IEGM: 183.6 +/- 16.3 ms; p < 0.001; correlation: R = 0.573, p = 0.066). VV delay showed significant differences for optimized delays (echo: 46.4 +/- 23.8 ms, IEGM: 10.9 +/- 7.0 ms; p <0.01; correlation: R = -0.278, p = 0.407). CONCLUSION: The automated programmer-based IEGM-based method provides a simple and safe method to perform CRT optimization. However, the reliability of this method appears to be limited. Thus, it remains difficult for the examiner to determine the optimal hemodynamic settings. Additionally, as there was no correlation between the optimal AV- and VV-delays calculated by the IEGM method and the echo optimization, the use of the IEGM method and the comparability to the echo has not been definitely clarified.