Predictors of pacing-induced cardiomyopathy detection and outcomes demonstration after conduction system pacing upgrade on patients with long-term persistent atrial fibrillation.

OBJECTIVE: To identify the predictors of pacing-induced cardiomyopathy (PICM) and illustrate the safety and feasibility of conduction system pacing (CSP) upgrade on patients with long-term persistent atrial fibrillation (AF). METHODS: All patients with long-term persistent AF and normal left ventricular ejection fraction (LVEF) ≥50% were consecutively enrolled from January 2008 to December 2017, and all the patients with atrioventricular block (AVB) and high right ventricular pacing (RVP) percentage of at least 40%. The predictors of PICM were identified, and patients with PICM were followed up for at least 1 year regardless of CSP upgrade. Cardiac performances and lead outcomes were investigated in all patients before and after CSP upgrade. RESULTS: The present study included 139 patients, out of which 37 (26.62%) developed PICM, resulting in a significant decrease in the left ventricular ejection fraction (LVEF) from 56.11 ± 2.56% to 38.10 ± 5.81% (p< .01). The median duration for the development of PICM was 5.43 years. Lower LVEF (≤52.50%), longer paced QRS duration (≥175 ms), and higher RVP percentage (≥96.80%) were identified as independent predictors of PICM. Furthermore, the morbidity of PICM progressively increased with an increased number of predictors. The paced QRS duration (183.90 ± 22.34 ms vs. 136.57 ± 20.71 ms, p < .01), LVEF (39.35 ± 2.71% vs. 47.50 ± 7.43%, p < .01), and left ventricular end-diastolic diameter (LVEDD) (55.53 ± 5.67 mm vs. 53.20 ± 5.78 mm, p = .03) improved significantly on patients accepting CSP upgrade. CSP responses and complete reverse remodeling (LVEF ≥50% and LVEDD < 50 mm) were detected in 80.95% (17/21) and 42.9% (9/21) of patients. The pacing threshold (1.52 ± 0.78 V/0.4 ms vs. 1.27 ± 0.59 V/0.4 ms, p = .16) was stable after follow-up. CONCLUSION: PICM is very common in patients with long-term persistent AF, and CSP upgrade was favorable for better cardiac performance in this patient population.

Conduction system pacing improves the outcomes on patients with high percentage of ventricular pacing and heart failure with mildly reduced ejection fraction.

Aims: This study aimed to investigate the efficacy and safety of CSP in patients with a high percentage of ventricular pacing and heart failure with HFmrEF. Methods: Patients who underwent CSP for HFmrEF and ventricular pacing >40% were consecutively enrolled from January 2018 to May 2021. All participants were followed up at least 12 months. Clinical data including cardiac performance and lead outcomes were compared before and after the procedure. Left ventricular ejection fraction (LVEF) was measured using the biplane Simpson's method. HFmrEF was defined as heart failure with the LVEF ranging from 41%-49%. Results: CSP was successfully performed in 64 cases (96.97%), which included 16 cases of left bundle branch pacing (LBBP) and 48 cases of His bundle pacing (HBP). After a mean of 23.12 ± 8.17 months follow-up, NYHA classification (P < 0.001), LVEF (42.45 ± 1.84% vs. 49.97 ± 3.57%, P < 0.001) and left ventricular end diastolic diameter (LVEDD) (55.59 ± 6.17 mm vs. 51.66 ± 3.48 mm, P < 0.001) improved significantly. During follow-up, more than half (39/64,60.9%) of patients returned to normal LVEF and LVEDD with complete reverse remodeling. The pacing threshold in LBBP was lower (0.90 ± 0.27 V@0.4 ms vs. 1.61 ± 0.71 V@0.4 ms, P < 0.001) than that in HBP. No perforation, electrode dislodging, thrombosis or infection was observed during follow-up. Conclusions: CSP could improve the clinical outcomes in patients with HFmrEF and a high percentage of ventricular pacing. LBBP might be a better choice because of its feasibility and safety, especially in patients with infranodal atrioventricular block.

Brady-arrhythmias in patients with atrial fibrillation and heart failure of reduced ejection fraction: is his-bundle pacing superior to biventricular pacing？.

OBJECTIVE: To investigate the efficacy and safety of His-bundle pacing (HBP) compared with the traditional biventricular pacing (BVP) on patients with brady-arrhythmias, who suffer from permanent atrial fibrillation (AF) and heart failure with reduced ejection fraction (HFrEF). METHODS: All patients with brady-arrhythmias, permanent AF and HFrEF were continuously enrolled from January 2017 to July 2019 and followed up for at least 12 months. The differences in QRS duration (QRSd), New York Heart Association (NYHA) classification, left ventricular ejection fraction (LVEF), tricuspid regurgitation grade, mitral regurgitation grade, left ventricular end-diastolic diameter (LVEDD), and left atrial size were compared. RESULTS: A total of 52 patients were enrolled: 37 patients were with HBP and 15 patients with BVP. There was no electrode dislodged, perforation, infection or thrombosis during the follow-up of 18.12 ± 4.45 months. The success rate for HBP implantation was 88.10%. The capture threshold of his-bundle and the threshold of the left ventricular lead remained stable during follow-up. LVEF increased to higher than 50% in 11 patients with HBP (29.73%). The NYHA classification (both p < .001), LVEF (both p < .001) and LVEDD improved significantly during the follow-up in both groups. NYHA (p = .030), LVEF (p = .013), and LVEDD (p = .003) improved in patients with HBP compared with BVP. CONCLUSION: HBP was safe and more effective in improving the cardiac function and remodeling in patients with brady-arrhythmias, permanent AF and HFrEF compared with BVP.

His-purkinje system pacing upgrade improve the heart performances in patients suffering from pacing-induced cardiomyopathy with or without permanent atrial fibrillation.

INTRODUCTION: The efficacy and safety of his-purkinje system pacing (HPSP) upgrades in patients with pacing-induced cardiomyopathy (PICM) and atrial fibrillation (AF) are still unknown. METHODS AND RESULTS: Patients with PICM were continuously enrolled from January 2018 to March 2020. All patients were further divided into AF subgroup and sinus rhythm subgroup. Clinical data including echocardiographic examination parameters, electrocardiogram (ECG) measurements, and New York Heart Association (NYHA) classification, were assessed before and after the procedure. The HPSP upgrades, including his bundle pacing (HBP) and left bundle branch pacing (LBBP) were completed in 34 of 36 (94%) patients, Complications including electrode dislodged, perforation, infection or thrombosis were not observed in the perioperative period. During a mean of 11.52 ± 5.40 months of follow-up. The left ventricular ejection fraction (LVEF) increased significantly (33.76 ± 7.54 vs 40.41 ± 9.06, P < 0.001), and the QRS duration decreased (184.22 ± 23.76 ms vs 120.52 ± 16.67 ms, P < 0.001) after the upgrades. LVEDD reversed from 59.29 ± 7.74 mm to 53.91 ± 5.92 mm (P < 0.001), and the NYHA functional class also improved to 2.00 ± 0.76 from 2.55 ± 0.91 at the first follow-up (P < 0.001). The left atrium (LA) size also slightly decreased compared to the initial state (47.44 ± 7.14 mm VS 45.56 ± 7.78, P = 0.010). BNP significantly decreased from a median value of 458.06(256.35-755.10) to 172.31(92.69-552.14) (P = 0.004). The threshold did not increase significantly (1.18 ± 0.76 mv@0.4 ms vs 1.26 ± 0.91mv @ 0.4 ms, P = 0.581). These improvements in patients with AF were similar with those in patients without AF (P > 0.05). CONCLUSIONS: HPSP upgrades improved the heart performance and reversed the left ventricular remodeling in patients suffering from PICM with or without AF, and it should be a promising choice in these patients.

Conservation Priorities Analysis of Chinese Indigenous Pig Breeds in the Taihu Lake Region.

Most indigenous pig resources are known to originate from China. Thus, establishing conservation priorities for these local breeds is very essential, especially in the case of limited conservation funds. Therefore, in this study, we analyzed 445 individuals belonging to six indigenous breeds from the Taihu Lake Region, using a total of 131,300 SNPs. In order to determine the long-term guidelines for the management of these breeds, we analyzed the level of diversity in the metapopulation following a partition of diversity within and between breed subpopulations, using both measures of genic and allelic diversity. From the study, we found that the middle Meishan (MMS) pig population contributes the most (22%) to the total gene diversity while the Jiaxing black (JX) pig population contributes the most (27%) to the gene diversity between subpopulations. Most importantly, when we consider one breed is removed from the meta-population, the first two breeds prioritized should be JX pig breed and Fengjing pig breed followed by small Meishan (SMS), Mizhu (MI), and Erhualian (EH) if we pay more attention to the gene diversity between subpopulations. However, if the priority focus is on the total gene diversity, then the first breed to be prioritized would be the Shawutou (SW) pig breed followed by JX, MI, EH, and Fengjing (FJ). Furthermore, we noted that if conservation priority is to be based on the allelic diversity between subpopulations, then the MI breed should be the most prioritized breed followed by SW, Erhuanlian, and MMS. Summarily, our data show that different breeds have different contributions to the gene and allelic diversity within subpopulations as well as between subpopulations. Our study provides a basis for setting conservation priorities for indigenous pig breeds with a focus on different priority criteria.

Selection signature reveals genes associated with susceptibility loci affecting respiratory disease due to pleiotropic and hitchhiking effect in Chinese indigenous pigs.

BACKGROUND: Porcine respiratory disease is one of the most important health problems which causes significant economic losses. OBJECTIVE: To understand the genetic basis for susceptibility to swine enzootic pneumonia (EP) in pigs, we detected 102,809 SNPs in a total of 249 individuals based on genome-wide sequencing data. METHODS: Genome comparison of three susceptibility to swine EP pig breeds (Jinhua, Erhualian and Meishan) with two western lines that are considered more resistant (Duroc and Landrace) using XP-EHH and FST statistical approaches identified 691 positively selected genes. Based on QTLs, GO terms and literature search, we selected 14 candidate genes that have convincible biological functions associated with swine EP or human asthma. RESULTS: Most of these genes were tested by several methods including transcription analysis and candidated genes association study. Among these genes: CYP1A1 and CTNNB1 are involved in fertility; TGFBR3 plays a role in meat quality traits; WNT2, CTNNB1 and TCF7 take part in adipogenesis and fat deposition simultaneously; PLAUR (completely linked to AXL, r2=1) plays an essential role in the successful ovulation of matured oocytes in pigs; CLPSL2 (strongly linked to SPDEF, r2=0.848) is involved in male fertility. CONCLUSION: These adverse genes susceptible to swine EP may be selected while selecting for economic traits (especially reproduction traits) due to pleiotropic and hitchhiking effect of linked genes. Our study provided a completely new point of view to understand the genetic basis for susceptibility or resistance to swine EP in pigs thereby, provide insight for designing sustainable breed selection programs. Finally, the candidate genes are crucial due to their potential roles in respiratory diseases in a large number of species, including human.

Exploring the Structure of Haplotype Blocks and Genetic Diversity in Chinese Indigenous Pig Populations for Conservation Purpose.

Chinese indigenous pigs in the Taihu Lake region are well known for their high fecundity and other excellent characteristics. To better understand the characteristics of these breeds in this area as well as to provide the government and breeders the molecular basis for formulating a reasonable conservation policy, we explored the structure of haplotype blocks and genetic diversity of the 7 populations which is relevant for the management and conservation of these important genetic resources using next-generation sequencing data. In this study, a total of 131 300 single-nucleotide polymorphisms with minor allele frequencies ⩾0.05 were obtained for further analysis. In general, there are similar within-breed genetic diversities (He, Ho, Pn, Ar) among these 7 pig populations in the Taihu Lake region. Average values for the inbreeding coefficients estimates in the 7 populations are 0.110 (F1), 0.056 (F2), and 0.078 (F3). All the breeds have seen a continuous decline in Ne estimates over time with FJ and SW populations having a very similar curve. Moreover, the Ne of SMS pig breeds were smaller than other Chinese pig breeds, indicating that SMS pig breeds underwent stronger selection pressure than other Chinese pig breeds. The average genetic distances among the 7 populations in the Taihu Lake region were 0.235 (MMS), 0.240 (SMS), 0.269 (EH), 0.248 (MI), 0.221 (FJ), 0.254 (JX), and 0.212 (SW). A summary of the number of haplotype blocks and haplotype diversity was also presented. This study provide a deep understanding of the current situation of conservation in this region, thereby uncovering the pertinent insight to better formulate more reasonable preservation policies for the government departments and breeding planners to follow-up.

Genomic analysis reveals genes affecting distinct phenotypes among different Chinese and western pig breeds.

The differences in artificial and natural selection have been some of the factors contributing to phenotypic diversity between Chinese and western pigs. Here, 830 individuals from western and Chinese pig breeds were genotyped using the reduced-representation genotyping method. First, we identified the selection signatures for different pig breeds. By comparing Chinese pigs and western pigs along the first principal component, the growth gene IGF1R; the immune genes IL1R1, IL1RL1, DUSP10, RAC3 and SWAP70; the meat quality-related gene SNORA50 and the olfactory gene OR1F1 were identified as candidate differentiated targets. Further, along a principal component separating Pudong White pigs from others, a potential causal gene for coat colour (EDNRB) was discovered. In addition, the divergent signatures evaluated by Fst within Chinese pig breeds found genes associated with the phenotypic features of coat colour, meat quality and feed efficiency among these indigenous pigs. Second, admixture and genomic introgression analysis were performed. Shan pigs have introgressed genes from Berkshire, Yorkshire and Hongdenglong pigs. The results of introgression mapping showed that this introgression conferred adaption to the local environment and coat colour of Chinese pigs and the superior productivity of western pigs.

The genetic connectedness calculated from genomic information and its effect on the accuracy of genomic prediction.

The magnitude of connectedness among management units (e.g., flocks and herds) gives a reliable estimate of genetic evaluation across these units. Traditionally, pedigree-based methods have been used to evaluate the genetic connectedness in China. However, these methods have not been able to yield a substantial outcome due to the lack of accuracy and integrity of pedigree data. Therefore, it is necessary to ascertain genetic connectedness using genomic information (i.e., genome-based genetic connectedness). Moreover, the effects of various levels of genome-based genetic connectedness on the accuracy of genomic prediction still remain poorly understood. A simulation study was performed to evaluate the genome-based genetic connectedness across herds by applying prediction error variance of difference (PEVD), coefficient of determination (CD) and prediction error correlation (r). Genomic estimated breeding values (GEBV) were predicted using a GBLUP model from a single and joint reference population. Overall, a continued increase in CD and r with a corresponding decrease in PEVD was observed as the number of common sires varies from 0 to 19 regardless of heritability levels, indicating increasing genetic connectedness between herds. Higher heritability tends to obtain stronger genetic connectedness. Compared to pedigree information, genomic relatedness inferred from genomic information increased the estimates of genetic connectedness across herds. Genomic prediction using the joint versus single reference population increased the accuracy of genomic prediction by 25% and lower heritability benefited more. Moreover, the largest benefits were observed as the number of common sires equals 0, and the gain of accuracy decreased as the number of common sires increased. We confirmed that genome-based genetic connectedness enhanced the estimates of genetic connectedness across management units. Additionally, using the combined reference population substantially increased accuracy of genomic prediction. However, care should be taken when combining reference data for closely related populations, which may give less reliable prediction results.

[Factors analysis and genetic parameter estimation of female reproductive traits in pigs].

Reproductive performance of stock sows is one of the important factors of economic impact in pig farms. In this study, 8491 litter records from 2699 sows of Yorkshire, Landrace, and Duroc were analyzed using fixed model to determine the effect of parity, mating season, and breed on total number born (TNB), number healthy birth (NHB), litter birth weight (LWB), number weak birth (NWB), stillbirth, mummy fetus, and deform fetus by the least square analysis. Genetic parameters of the above traits were estimated by restricted maximum likelihood (REML) procedure. In addition, the effectiveness of pure-breeding and cross-breeding on litter performance were compared. The results showed that, parity, mating season, and breed had significant effect on TNB, NHB, and LWB(P < 0.001).The effects of parity and breed were significant on NWB(P < 0.001), while mating season had non-significant effect on NWB. Parity showed significant effect on stillbirth, while the effect of mating season and breed was not significant. Parity, mating season, and breed had no significant effect on mummy fetus and deform fetus. Landrace♂×Large White♀ showed the best litter performance, including TNB, NHB, and LWB. Moreover, LWB of Landrace depicted the highest heritability, while other traits were all bellow 0.2. The genetic correlation between TNB and NHB, NHB and LWB were higher than 0.96 in the three breeds. These results provided reference data for minimizing low-reproductive performance caused by non-infectious factors and improving sow reproductive performance in pig farms.

Comparison of five methods for genomic breeding value estimation for the common dataset of the 15th QTL-MAS Workshop.

BACKGROUND: Genomic breeding value estimation is the key step in genomic selection. Among many approaches, BLUP methods and Bayesian methods are most commonly used for estimating genomic breeding values. Here, we applied two BLUP methods, TABLUP and GBLUP, and three Bayesian methods, BayesA, BayesB and BayesCπ, to the common dataset provided by the 15th QTL-MAS Workshop to evaluate and compare their predictive performances. RESULTS: For the 1000 progenies without phenotypic values, the correlations between GEBVs by different methods ranged from 0.812 (GBLUP and BayesCπ) to 0.997 (TABLUP and BayesB). The accuracies of GEBVs (measured as correlations between true breeding values (TBVs) and GEBVs) were from 0.774 (GBLUP) to 0.938 (BayesCπ) and the biases of GEBVs (measure as regressions of TBVs on GEBVs) were from 1.033 (TABLUP) to 1.648 (GBLUP). The three Bayesian methods and TABLUP had similar accuracy and bias. CONCLUSIONS: BayesA, BayesB, BayesCπ and TABLUP performed similarly and satisfactorily and remarkably outperformed GBLUP for genomic breeding value estimation in this dataset. TABLUP is a promising method for genomic breeding value estimation because of its easy computation of reliabilities of GEBVs and its easy extension to real life conditions such as multiple traits and consideration of individuals without genotypes.

Genome-wide association analyses of the 15th QTL-MAS workshop data using mixed model based single locus regression analysis.

BACKGROUND: The mixed model based single locus regression analysis (MMRA) method was used to analyse the common simulated dataset of the 15th QTL-MAS workshop to detect potential significant association between single nucleotide polymorphisms (SNPs) and the simulated trait. A Wald chi-squared statistic with df =1 was employed as test statistic and the permutation test was performed. For adjusting multiple testing, phenotypic observations were permutated 10,000 times against the genotype and pedigree data to obtain the threshold for declaring genome-wide significant SNPs. Linkage disequilibrium (LD) in term of D' between significant SNPs was quantified and LD blocks were defined to indicate quantitative trait loci (QTL) regions. RESULTS: The estimated heritability of the simulated trait is approximately 0.30. 82 genome-wide significant SNPs (P < 0.05) on chromosomes 1, 2 and 3 were detected. Through the LD blocks of the significant SNPs, we confirmed 5 and 1 QTL regions on chromosomes 1 and 3, respectively. No block was detected on chromosome 2, and no significant SNP was detected on chromosomes 4 and 5. CONCLUSION: MMRA is a suitable method for detecting additive QTL and a fast method with feasibility of performing permutation test. Using LD blocks can effectively detect QTL regions.

[Comparative analysis on content and distribution of CpG sites in milk production traits and mastitis-related genes in dairy cattle].

DNA methylation is a major part of epigenetics. DNA methylation on the CpG sites in gene promoter and the first exon often represses gene expression, but demethylation activates gene expression. Previous research has shown that a negative correlation was found between mastitis index (somatic cell count, SCC) and milk production traits in Holsteins. The content and distribution of CpG dinucleotide sites in different regions of the candidate genes related to milk production traits and mastitis were studied in the present study. The regions contained promoter (2000 bp upstream of transcriptional start site), exon 1, and 2000 bp downstream of transcriptional end site. The CpG number of promoter and exon 1 in the mastitis-related genes was significantly less than that of the milk production-associated genes. However, the CpG number of 2000 bp downstream of the genes for the two traits was not significantly different. Two new index quantified CpG characterizations were proposed. One is the CpG distance, which can measure the distribution of CpG. The other is the conditional probability p(G|C), which is used to quantify the probability of CpG in a nucleotide sequence along with C. The two indexes of promoter and exon 1 in the two types of genes and their statistic analysis were carried out. This study sets the basis for DNA methylation regulation of milk production traits- and mastitis-related genes.

[Chinese Holstein Cattle effective population size estimated from whole genome linkage disequilibrium].

Effective populations size (Ne) is an important population parameter that helps to explain genetic variation, population evolution and understanding of the genetic architecture underlying complex traits. With the availability of high-dense SNP panels, more and more researches focus on estimating of Ne using linkage disequilibrium (LD) between SNPs. In this study, we estimated the effective population size from 2093 Chinese Holstein Cattle genotyped with Illumina BovineSNP50 BeadChip. After removal of individual with call rate lt; 95%, SNPs with call rate lt; 95%, minor allele frequency lt; 5% and Hardy-Weinberg Equilibrium test with Plt;0.0001, 1 968 individuals with 38 796 SNPs were remained. Eight kinds of SNP pairs with the distances 0.1, 0.2, 0.5, 1, 2, 5, 10, and 15 Mb were respectively chosen to estimate the effective population size of Chinese Holstein cattle from 4 generations ago. It is demonstrated from the results of this study that the effective population size of Chinese Holstein is decreased in the past generations, and the corresponding effective population size at ~4 generations ago is only around 45.