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BACKGROUND: Left atrial (LA) dimension ≥50 mm had approximately four times the risk of developing atrial fibrillation (AF). The aim of this study was to investigate whether the application of clinical and echocardiographic parameters could differentiate between the patients having severely dilated left atrium with and without AF. METHODS: This retrospective cross-sectional study enrolled consecutive patients with LA dimension ≥50 mm and divided them into three groups: no AF (no-AF), paroxysmal AF (PAF) and non-paroxysmal AF (non-PAF) groups. For PAF and non-PAF groups, all patients underwent radiofrequency ablation, and the echocardiographic parameters were obtained on the next day after ablation. RESULTS: Our study population comprised 160 patients, including 80, 53, and 27 patients in the non-AF, PAF and non-PAF groups, respectively. The no-AF group had a significantly higher body mass index (kg/m(2)) (29.31±6.27, 27.58±4.12 and 26.57±2.81, P=0.01), and a higher prevalence of diabetes mellitus (DM) [31 (38.80%), 13 (25.00%) and 4 (14.80%), P=0.01] and hypertension [67 (83.80%), 34 (65.40%), and 19 (70.40%), P=0.04], but a lower prevalence of rheumatic heart disease (RHD) [3 (3.80%), 6 (11.50%) and 5 (18.50%), P=0.02] and sick sinus syndrome [0 (0.00%), 6 (11.50%) and 4 (14.80%), P=0.045]. Echocardiographic studies showed that the non-AF group had significantly smaller LA minimal volume index (24.89±9.74, 34.06±19.38 and 42.83±17.44 mL/m(2), P

The evolution of diverse phenotypes both involves and is constrained by molecular interaction networks. When these networks influence patterns of expression, we refer to them as gene regulatory networks (GRNs). Here, we develop a model of GRN evolution analogous to work from quasi-species theory, which is itself essentially the mutation–selection balance model from classical population genetics extended to multiple loci. With this GRN model, we prove that—across a broad spectrum of selection pressures—the dynamics converge to a stationary distribution over GRNs. Next, we show from first principles how the frequency of GRNs at equilibrium is related to the topology of the genotype network, in particular, via a specific network centrality measure termed the eigenvector centrality. Finally, we determine the structural characteristics of GRNs that are favoured in response to a range of selective environments and mutational constraints. Our work connects GRN evolution to quasi-species theory—and thus to classical populations genetics—providing a mechanistic explanation for the observed distribution of GRNs evolving in response to various evolutionary forces, and shows how complex fitness landscapes can emerge from simple evolutionary rules.

Purpose The 6-min walk test (6MWT) is a useful tool to assess the physiologic function in patients with chronic obstructive pulmonary disease (COPD). The recent study showed that patients with COPD with oxygen desaturation during the 6MWT had an increased risk of exacerbation and death compared with those without oxygen desaturation. This study aimed to explore the potential risk factors for exercise-induced desaturation (EID) in patients with COPD. Patients and Methods Adult patients with COPD were enrolled from the Chang Gung Research Database between January 2013 and January 2017. Age, sex, body mass index, underlying diseases, medications, and results of the pulmonary function tests and 6MWT were retrospectively collected and analyzed. Results Among 1768 patients with COPD, 932 (52.7%) had oxygen desaturation, and the other 836 (47.3%) had no desaturation during the 6MWT. The patients with EID had a shorter 6-min walk distance than those without desaturation (352.08±120.29 vs 426.56±112.56, p

Over 100 years, Fitness landscapes have been a powerful metaphor for understanding the evolution of biological systems. These landscapes describe how genotypes are connected to each other and are related according to relative fitness. Despite the high dimensionality of such real-world landscapes, empirical studies are often limited in their ability to quantify the fitness of different genotypes beyond point mutations, while theoretical works attempt statistical/mechanistic models to reason the overall landscape structure. However, most classical fitness landscape models overlook an instinctive constraint that genotypes leading to the same phenotype almost certainly share the same fitness value, since the information of genotype-phenotype mapping is rarely incorporated. Here, we investigate fitness landscape models through the lens of Gene Regulatory Networks (GRNs), where the regulatory products are computed from multiple genes and collectively treated as the phenotypes. With the assumption that regulatory mediators/products exhibit binary states, we prove topographical features of GRN fitness landscape models such as accessibility and connectivity insensitive to the choice of the fitness function. Furthermore, using graph theory, we deduce a mesoscopic structure underlying GRN fitness landscape models that retains necessary information for evolutionary dynamics with minimal complexity. We also propose an algorithm to construct such a mesoscopic backbone which is more efficient than the brute-force approach. Combined, this work provides mathematical implications for fitness landscape models with high-dimensional genotype-phenotype mapping, yielding the potential to elucidate empirical landscapes and their resulting evolutionary processes in a manner complementary to existing computational studies.

Background Acute kidney injury (AKI) is a common complication of acute myocardial infarction (AMI), and is associated with adverse outcomes. The study aimed to identify a miRNA signature for the early diagnosis of post-AMI AKI. Methods A total of 108 patients admitted to a coronary care unit (CCU) were divided into four subgroups: AMI−AKI−, AMI+AKI−, AMI+AKI+, and AMI−AKI+. Thirty-six miRNA candidates were selected based on an extensive literature review. Real-time quantitative RT-PCR analysis was used to determine the expression levels of these miRNAs in the serum collected on the day of CCU admittance. TargetScan 7.1 and miRDB databases were used for target prediction and Metacore 6.13 was used for pathway analysis. Results Through a stepwise selection based on abundance, hemolytic effect and differential expression between four groups, 9 miRNAs were found to have significantly differential expression levels as potential biomarkers for post-AMI AKI specifically. Noticeably, the expression levels of miR-24, miR-23a and miR-145 were significantly down-regulated in AMI+AKI+ patients compared to those in AMI+AKI− patients. Combination of the three miRNAs as a panel showed the best performance in the early detection of AKI following AMI (AUC = 0.853, sensitivity 95.65%), compared to the analysis of serum neutrophil gelatinase-associated lipocalin (AUC = 0.735, sensitivity 63.16%). Furthermore, bioinformatic analysis indicated that these three miRNAs regulate the transforming growth factor beta signaling pathway and involve in apoptosis and fibrosis in AKI. Conclusions For the first time, this study identify a unique circulating miRNA signature (miR-24-3p, miR-23a-3p, miR-145-5p) that can potentially early detect AKI following AMI and may be involved in renal injury and fibrosis in post-AMI AKI pathogenesis. Electronic supplementary material The online version of this article (10.1186/s12967-019-1890-7) contains supplementary material, which is available to authorized users.

BACKGROUND: Older patients with aortic stenosis (AS) have a higher incidence of wild-type transthyretin cardiac amyloidosis (ATTR-CA). This study aimed to determine whether apical sparing of longitudinal strain (LS) could help diagnose ATTR-CA and provide useful prognostic information in symptomatic AS. METHODS: We performed vendor-independent two-dimensional speckle-tracking analysis of regional and global left ventricular LS in 16 patients with ATTR-CA and 31 patients with non-obstructive hypertrophic cardiomyopathy to determine the best cutoff value of the apical sparing ratio (APSR) for diagnosing ATTR-CA. We then determined the prevalence in patients who had an APSR higher than the best cutoff value and investigated its prognostic value in 230 patients with symptomatic AS. To determine the natural history of symptomatic AS, patients who had aortic valve replacement were censored at the time of surgery. RESULTS: The best cutoff value of APSR was 0.76. APSR ≥ 0.76 was observed in 108 patients with symptomatic AS (48%). The prevalence was not different among the four AS subgroups. During a median follow-up period of 5.7 months, 47 patients had cardiac events. Cox proportional hazards analysis revealed that neither APSR nor APSR ≥ 0.76 was significantly associated with future cardiac events. CONCLUSIONS: Apical sparing was frequently observed in patients with symptomatic AS, and it was not a useful predictor of future adverse outcomes. Our results suggest that the underlying cause of apical sparing in AS may not be related to the presence of ATTR-CA.

This study demonstrates the capacitive type humidity sensor design with novel fringe-effect sensing electrodes and polyimide-pillar array, as shown in Fig. 1. The sensor is implemented by the TSMC 0.18µm 1P6M CMOS platform and also monolithically integrated with thermometer and micro heater for performance enhancement. The presented humidity sensing unit has two major merits: (1) polyimide-pillar array: to enhance water vapor absorption and improve the response time; (2) fringe capacitive sensing electrodes: for easy integration with the polyimide-pillars and also to prevent the cross-talk from heater; and the proposed design also features with: (3) vertical integration of micro heater: to prevent water vapor condensation; (4) backside silicon etching: for thermal isolation; (5) monolithic integration of thermometer: for signal calibration. Measurements show the response time of proposed humidity sensor have 43% enhance after plasma etching, and also demonstrate the performances of heater and thermometer. Simulations further indicate a 1.5-fold sensing signal enhancement compared with parallel electrodes.

Patients with chronic kidney disease (CKD) and coronary instent restenosis (ISR) treated with drug-coated balloon (DCB) angioplasty have been excluded from randomized controlled trials. We aimed to investigate the clinical impact of CKD stratified by severity, on clinical outcomes for patients with ISR treated with DCB angioplasty.This cohort study enrolled 1,376 patients treated with DCB angioplasty; 639 CKD patients defined as having an estimated glomerular filtration rate (eGFR)60 mL/min/1.73 m2 and 737 patients with preserved renal function were identified. Risks of target vessel failure (TVF), all-cause mortality, and any repeated revascularization were analyzed.The CKD group had a significantly higher risk of TVF [adjusted hazard ratio (HR): 1.337; 95% confidence interval (CI): 1.125-1.590; p = 0.0010], all-cause mortality (adjusted HR: 2.553; 95% CI: 1.494-4.361; p = 0.0006), and any repeated revascularization (adjusted HR: 1.447; 95% CI: 1.087-1.927; p = 0.0114) compared with the non-CKD group. After multivariable adjustment, patients with severe CKD (eGFR = 15-29 mL/min/1.73 m2) and end-stage renal disease (ESRD) (eGFR15 mL/min/1.73 m2) had a significantly higher risk of adverse events comparable to that in patients with preserved renal function.In this cohort study, patients with CKD and ISR undergoing DCB angioplasty had a significantly higher risk of adverse events compared with patients with preserved renal function, whereas subgroups with mild to moderate CKD did not display this difference. Different revascularization strategies may be considered for patients with severe CKD or ESRD with ISR.

The evolution of diverse phenotypes both involves and is constrained by molecular interaction networks. When these networks influence patterns of expression, we refer to them as gene regulatory networks (GRNs). Here, we develop a quasi-species model of GRN evolution. With this model, we prove that–across a broad spectrum of viability and mutation functions–the dynamics converge to a stationary distribution over GRNs. Next, we show from first principles how the frequency of GRNs at equilibrium will be proportional to each GRN’s eigenvector centrality in the genotype network. Finally, we determine the structural characteristics of GRNs that are favored in response to a range of selective environments and mutational constraints. Our work connects GRN evolution to quasi-species models, and thus can provide a mechanistic explanation for the topology of GRNs experiencing various evolutionary forces.

The aim of this study was to evaluate the effect of beta-blockers, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) after cardiac surgery in the liver cirrhosis (LC) patients. We conducted a population-based cohort study using data from the Taiwanese National Health Insurance Research Database (NHIRD) from 2001 to 2013. The outcomes of interest included all-cause mortality, major adverse cardiac and cerebrovascular events (MACCE) and liver and renal outcomes. Among 1470 LC patients, 35.6% (n = 524) received beta-blockers and 33.4% (n = 491) were prescribed ACEIs and/or ARBs after cardiac surgery. The risk of negative liver outcomes was significantly lower in the ARB group compared with the ACEI group (9.6% vs 22.7%, hazard ratio [HR] 0.50, 95% confidence interval [CI] 0.31-0.83). Furthermore, the risk of MACCE (44.2% vs 54.7%, HR 0.79, 95% CI 0.65-0.96), all-cause mortality (35.3% vs 46.4%, HR 0.74, 95% CI 0.60-0.92), composite liver outcomes (9.6% vs 16.5%, HR 0.56, 95% CI 0.38-0.85) and hepatic encephalopathy (2.7% vs 5.7%, HR 0.45, 95% CI 0.21-0.94) were lower in the ARB group than the control group. Our study demonstrated that ARBs provide a greater protective effect than ACEIs in regard to long-term outcomes following cardiac surgery in patients with LC.

The cover image is based on the Original Paper Fixed‐dose combination of amlodipine and atorvastatin improves clinical outcomes in patients with concomitant hypertension and dyslipidemia by Chia‐Pin Lin, Ying‐Chang Tung et al., https://doi.org/10.1111/jch.14016. [Image: see text]

BACKGROUND: Acute coronary syndrome (ACS) is a life-threatening medical condition that accounts for an annual expenditure of more than $300 billion in the United States. Hospital accreditation has been shown to improve patient and hospital outcomes for various conditions. OBJECTIVES: This study aimed to determine the benefits of hospital accreditation in patients with ACS. METHODS: This nationwide population-based cohort study used Taiwan’s National Health Insurance Research Database from 1997 to 2011 (n = 249,354). Multivariable logistic regression was used to analyze the risk of in-hospital events among those treated in accredited and non-accredited hospitals, and to compare outcomes in hospitals before and after accreditation. The effect of accreditation on these events was also stratified by accreditation grade. RESULTS: A total of 823 hospitals were included, of which 2.4% were medical centers, 13.7% were regional hospitals, and 83.8% were district hospitals. The in-hospital mortality [odds ratio (OR), 0.82; 95% confidence interval (CI), 0.79-0.85; p < 0.001] and recurrent acute myocardial infarction (AMI) admission (OR, 0.81; 95% CI, 0.71-0.93; p = 0.003) rates were significantly lower in the after-accreditation group than in the before-accreditation group. There was a substantial and marked decrease in the in-hospital mortality rate after accreditation in 2008. CONCLUSIONS: This cohort study demonstrated that ACS accreditation was associated with better in-hospital mortality and recurrent AMI admission rates in ACS patients.

BackgroundThis study analyzed the survival and protective predictors of in-hospital cardiopulmonary cerebral resuscitation (CPCR) to potentially help physicians create effective treatment plans for End-stage kidney disease (ESKD) patients.MethodsWe extracted the data of 7,116 ESKD patients who received their first in-hospital CPCR after initial dialysis between 2004 and 2012 from the National Health Insurance Research Database. The primary outcome was the survival rate during the first in-hospital CPCR. The secondary outcome was the median post-discharge survival.ResultsFrom 2004 through 2012, the incidence of in-hospital CPCR decreases from 3.97 to 3.67 events per 1,000 admission days (P for linear trend ConclusionThe incidence of in-hospital CPCR and the duration post-discharge among ESKD patients improved despite there being no significant difference in the survival rate of ESKD patients after CPCP. Either ICD or CRT-D implantation may be advisable for ESKD patients with a high risk of sudden cardiac death.

Purpose The 6-min walk test (6MWT) is a useful tool to assess the physiologic function in patients with chronic obstructive pulmonary disease (COPD). The recent study showed that patients with COPD with oxygen desaturation during the 6MWT had an increased risk of exacerbation and death compared with those without oxygen desaturation. This study aimed to explore the potential risk factors for exercise-induced desaturation (EID) in patients with COPD. Patients and Methods Adult patients with COPD were enrolled from the Chang Gung Research Database between January 2013 and January 2017. Age, sex, body mass index, underlying diseases, medications, and results of the pulmonary function tests and 6MWT were retrospectively collected and analyzed. Results Among 1768 patients with COPD, 932 (52.7%) had oxygen desaturation, and the other 836 (47.3%) had no desaturation during the 6MWT. The patients with EID had a shorter 6-min walk distance than those without desaturation (352.08±120.29 vs 426.56±112.56, p

Hypertension and dyslipidemia are important risk factors for cardiovascular disease. However, the clinical outcomes of fixed-dose combination (FDC) versus free-equivalent combination (FEC) of amlodipine and atorvastatin in the treatment of concurrent hypertension and dyslipidemia remain unknown. In this study, we included patients with newly diagnosed hypertension and dyslipidemia, without previously established cardiovascular disease, and treated with either FDC or FEC of amlodipine and atorvastatin were identified from the National Health Insurance Research Database of Taiwan and follow-up for 5 years. By using 1:1 propensity score matching, a total of 1756 patients were enrolled in this study. The composite of major adverse cardiovascular events, including all-cause mortality, myocardial infarction (MI), stroke, and coronary revascularization, occurred more frequently in the FEC group than in the FDC group (hazard ratio, 1.88; 95% confidence interval [CI], 1.42 to 2.5). Although the all-cause mortality did not differ (hazard ratio, 0.46; 95% CI, 0.36 to 1.59), the FEC group developed increased MI, stroke, and coronary revascularization (hazard ratio, 2.87; 95% CI, 1.07 to 7.68; hazard ratio, 1.97; 95% CI, 1.41 to 2.74; and hazard ratio, 2.44; 95% CI, 1.26 to 4.69, respectively). Furthermore, as an unexpected result, a higher risk to develop new-onset diabetes mellitus was observed with FEC regimens (hazard ratio, 2.19; 95% CI, 1.6 to 3.0). In conclusion, although the all-cause mortality did not differ between the two groups, the FDC regimen of amlodipine and atorvastatin improved clinical outcomes when compared to FEC in patients with newly diagnosed hypertension and dyslipidemia.

Molecular analyses of closely related taxa have increasingly revealed the importance of higher-order genetic interactions in explaining the observed pattern of reproductive isolation between populations. Indeed, both empirical and theoretical studies have linked the process of speciation to complex genetic interactions. Gene Regulatory Networks (GRNs) capture the inter-dependencies of gene expression and encode information about an individual’s phenotype and development at the molecular level. As a result, GRNs can–in principle–evolve via natural selection and play a role in non-selective, evolutionary forces. Here, we develop a network-based model, termed the pathway framework, that considers GRNs as a functional representation of coding sequences. We then simulated the dynamics of GRNs using a simple model that included natural selection, genetic drift, and sexual reproduction and found that reproductive barriers can develop rapidly between allopatric populations experiencing identical selection pressure. Further, we show that alleles involved in reproductive isolation can predate the allopatric separation of populations and that the number of interacting loci involved in genetic incompatibilities, i.e., the order, is often high simply as a by-product of the networked structure of GRNs. Finally, we discuss how results from the pathway framework are consistent with observed empirical patterns for genes putatively involved in post-zygotic isolation. Taken together, this study adds support for the central role of gene networks in speciation and in evolution more broadly.

BACKGROUND: The durable polymers (DP) used in first-generation drug-eluting stents (DESs) were associated with long-term cardiovascular events, and thus biodegradable polymer DESs (BP-DESs) and second-generation DP-DESs were designed to overcome this problem. In this study, we compared angiographic follow-up and long-term clinical outcomes between patients who received BP-DESs or second-generation DP-DESs. METHODS: We enrolled 436 patients with single coronary lesions who received a second-generation DP-DES or BP-DES between June 2009 and October 2012. All patients received follow-up angiography when new clinical events developed or at 9 months after index stenting. All participants received follow-up for 5 years. RESULTS: There were no significant differences in patient and lesion characteristics between the two groups. The 9-month angiographic follow-up showed a lower net gain in the second-generation DP-DES group (2.19 mm vs. 2.41 mm, p = 0.040), but a similar binary restenosis rate between the two groups (5.4% vs. 8.7%, p = 0.276). During the 5-year follow-up period, no significant differences were observed between the two groups in major adverse cardiac events (MACEs), cardiovascular death, nonfatal myocardial infarction (MI), target vessel revascularization (TVR), all revascularization, stent thrombosis (ST), or MACE-free survival. CONCLUSIONS: No significant differences were observed in cardiovascular death, nonfatal MI, TVR, all revascularization, ST, or MACE-free survival between the patients undergoing single coronary artery stenting with BP-DESs and second-generation DP-DESs.

The ongoing COVID-19 outbreak has expanded rapidly throughout China. Major behavioral, clinical, and state interventions are underway currently to mitigate the epidemic and prevent the persistence of the virus in human populations in China and worldwide. It remains unclear how these unprecedented interventions, including travel restrictions, have affected COVID-19 spread in China. We use real-time mobility data from Wuhan and detailed case data including travel history to elucidate the role of case importation on transmission in cities across China and ascertain the impact of control measures. Early on, the spatial distribution of COVID-19 cases in China was well explained by human mobility data. Following the implementation of control measures, this correlation dropped and growth rates became negative in most locations, although shifts in the demographics of reported cases are still indicative of local chains of transmission outside Wuhan. This study shows that the drastic control measures implemented in China have substantially mitigated the spread of COVID-19., One sentence summary: The spread of COVID-19 in China was driven by human mobility early on and mitigated substantially by drastic control measures implemented since the end of January.

Severe neurological complications following infective endocarditis remain a major problem with high mortality rate. The long-term neurological consequences following infective endocarditis remain uncertain. Otherwise, neurosurgeries could be performed after these complications; however, few clinical series have reported the results. Therefore, we utilized a large, nationwide database to unveil the long-term mortality and neurosurgical outcome following infective endocarditis. We included patients with a first-time discharge diagnosis of infective endocarditis between January 2001 and December 2013 during hospitalization. Patients were further divided into subgroups consisting of neurological complications under neurosurgical treatment and complications under non-neurosurgical treatment. Long-term result of symptomatic neurological complications after infective endocarditis and all-cause mortality after different kinds of neurosurgeries were analyzed. There were 16,495 patients with infective endocarditis included in this study. Symptomatic neurological complications occurred in 1,035 (6.27%) patients, of which 279 (26.96%) accepted neurosurgical procedures. Annual incidence of neurological complications gradually increased from 3.6% to 7.4% (P P = 0.012, increased from 20% initially to nearly 50% over the 5-year follow-up). However, neurosurgery had no effect on the long-term mortality rate (50.9% vs. 47.6%, P = 0.451). Incidence of neurological complications post-infective endocarditis is increasing, and patients with these complications have higher mortality rates than patients without. Neurosurgery in these populations was not associated with higher long-term mortality. Therefore, it should not be ruled out as an option for those with neurological complications.

Over the last two decades, alongside the increased availability of large network datasets, we have witnessed the rapid rise of network science. For many systems, however, the data we have access to is not a direct description of the underlying network. More and more, we see the drive to study networks that have been inferred or reconstructed from non-network data---in particular, using time series data from the nodes in a system to infer likely connections between them. Selecting the most appropriate technique for this task is a challenging problem in network science. Different reconstruction techniques usually have different assumptions, and their performance varies from system to system in the real world. One way around this problem could be to use several different reconstruction techniques and compare the resulting networks. However, network comparison is also not an easy problem, as it is not obvious how best to quantify the differences between two networks, in part because of the diversity of tools for doing so. The netrd Python package seeks to address these two parallel problems in network science by providing, to our knowledge, the most extensive collection of both network reconstruction techniques and network comparison techniques (often referred to as graph distances) in a single library (https://github.com/netsiphd/netrd). In this article, we detail the two main functionalities of the netrd package. Along the way, we describe some of its other useful features. This package builds on commonly used Python packages and is already a widely used resource for network scientists and other multidisciplinary researchers. With ongoing open-source development, we see this as a tool that will continue to be used by all sorts of researchers to come.

Irisin is an exercise-related myokine. The abundance of irisin is associated with many diseases, such as myocardial infarction, chronic kidney disease, metabolic syndrome, obesity, and diabetes mellitus. In cardiomyocytes, irisin modulates the mitochondrial thermogenesis, regulates ischemic responses, and affects calcium signaling. Previous studies suggested that irisin increases cardiomyoblast mitochondrial functions and protects ischemic and reperfusion injury in ex vivo murine heart. In human, clinical studies have shown that acute myocardial infarction patients with more elevated serum irisin abundances are associated with increased major adverse cardiovascular events. However, the mechanisms responsible for this discrepancy between in myocardial infarction patients and ex vivo murine heart is unclear. Based on the clinical observations, we hypothesized that excessive irisin might lead to mitochondrial dysfunctions and cardiomyocyte damages. Our data showed that overexpression of irisin in mice with the adenovirus resulted in enhanced mitochondrial respiration with a higher oxygen consumption rate. Enhanced irisin expression in heart and irisin treatment in cardiomyocytes increased reactive oxygen species production. Furthermore, irisin treatment in cardiomyocytes enhanced the apoptosis and the cleaved caspase 9 levels in hypoxic condition. Pathway analysis in the murine heart with the overexpression of irisin showed that angiopoietin-Tie2, IL-8, IL-13, TGF-β, and thrombopoietin signaling were affected by irisin. Collectively, these results supported that excessive irisin causes mitochondrial overdrive with a higher reactive oxygen species production, which results in increased apoptosis of cardiomyocytes in a hypoxic environment.

The therapeutic effects of reperfusion strategies with complete revascularization (CR) or incomplete revascularization (IR) in non-ST segment myocardial infarction (NSTEMI) patients with multivessel disease (MVD) are controversial. In such patients, whether utilization of different generations of drug-eluting stents (DES) for IR or CR affect long-term major adverse cardiovascular events (MACE) is unknown. This study included 702 NSTEMI patients with MVD who received first-generation (1G) or second-generation (2G) DES. In multivariable analysis, chronic kidney disease, chronic total, 1G DES and IR were independent predictors of long-term MACE. In patients receiving 1G DES, no significant differences of MACE were observed between the IR and CR groups (39.1% vs. 36.2%, p = 0.854). However, in patients receiving 2G DES, significantly fewer MACE were observed in the CR group than in the IR group (3.7% vs. 10.2%, p = 0.002). Compared with patients receiving 1G DES for IR, those receiving 2G DES for IR and CR exhibited significantly lower risk of MACE (59% and 83% lower, respectively). CR could not provide clinical benefits over IR in NSTEMI patients with MVD receiving 1G DES. However, in patients receiving 2G DES, compared with IR, CR was associated with a lower risk of long-term MACE, which was mainly caused by low rates of non-TLR and any revascularization.

Background Clinical trials have investigated efficacy of drug-eluting balloon (DEB) angioplasty for bare-metal stent (BMS) in-stent restenosis (ISR). Few studies have investigated predictors of long-term outcomes following BMS-ISR treatment with DEB. Methods From June 2011 to April 2015, 105 patients with 125 BMS-ISR lesions were enrolled from the Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions (CAPTAIN) registry. All these lesions were treated with DEB angioplasty as final therapy. The major adverse cardiac events (MACEs) were recurrent clinically driven target lesion revascularisation (TLR), myocardial infarction, and cardiac death after DEB angioplasty. Results After DEB angioplasty, the angiographic stenosis decreased from 84.8% ± 12.4% to 22.6% ± 10.4%. Over a mean follow-up duration of 21.7 ± 13.4 months, the rates of TLR at 1–12 months and 12–48 months were 4.8% and 4.2%, respectively. The rates of MACEs at 1–12 months and 12–48 months were 6.7% and 6.1%, respectively. Chronic haemodialysis, calcified lesion, chronic total occlusion lesion before stenting, stent with metal-to-artery ratio >16.5%, and residual stenosis >25% after DEB angioplasty were potential risk factors for MACEs in univariate analysis. After adjustment in multivariate analysis, independent predictors of long-term MACEs were identified as chronic haemodialysis, chronic total occlusion lesion before stenting, and residual stenosis >25% after DEB angioplasty. Conclusions The long-term results of DEB angioplasty for BMS-ISR are acceptable in this real-world registry. Patient (chronic haemodialysis), lesion (chronic total occlusion) and angioplasty (residual stenosis percentage) related factors predicted long-term outcomes following BMS-ISR treatment with DEB angioplasty.

BACKGROUND Data regarding the long-term outcomes of a large patient population with multivessel coronary artery disease (MV-CAD) after complete revascularization (CR) and incomplete revascularization (IR) with drug-eluting stent (DES) implantation are controversial. The objective of this study was to evaluate differences between the clinical outcomes of CR and IR in such patients.Methods and Results:A total of 1,502 patients with MV-CAD who received DES between April 2005 and August 2016 were enrolled in this study after propensity score matching. The CR group had 751 patients with 1,368 stents implanted in 1,215 lesions, and the IR group had 751 patients with 1,077 stents implanted in 948 lesions. The CR group had a similar rate of in-hospital major adverse cardiovascular events to the IR group (1.9% vs. 1.6%, P=0.844). Follow-up angiography at 9 months showed no significant difference between the 2 groups for restenosis. The CR group had a higher cardiovascular event-free survival rate than the IR group during a mean follow-up period of 71±62 months (81.8% vs. 72.0%, P

Data on a large patient population regarding very long-term outcomes after bare metal stent (BMS) implantation in diabetic patients are lacking. The aim of this study was to evaluate the very long-term (8-17 years) clinical and 6-month angiographic outcomes of BMS implantations in patients with and without type 2 diabetes.A total of 2391 patients (579 with and 1812 without diabetes) who received BMS implantations between November 1995 and May 2004 were enrolled from the Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions (CAPTAIN) registry into this study. During a mean follow-up period of 152±53months, the diabetic patients had higher rates of all-cause mortality (28% vs. 15%, p0.001), re-infarction (6% vs. 5%, p=0.284), target lesion revascularization (13% vs. 10%, p=0.049), and a lower cardiovascular event-free survival rate (42% vs. 56%, p0.001) compared to the patients without diabetes. The diabetic patients also had a higher restenosis rate (26% vs. 18%, p0.001) at 6-month angiographic follow-up. The multivariate analysis of risk factors for cardiac event-free survival included age (hazard ratio [HR]: 1.011; p=0.001), hypertension (HR: 1.168; p=0.011), diabetes mellitus (HR: 1.353; p0.001), pre-existing coronary artery disease (HR: 1.341; p0.001), and left ventricular ejection fraction (LVEF) (HR: 0.992; p=0.002) (Table 7). The Kaplan-Meier analysis showed a significant difference in cardiovascular event-free survival rate between the two groups (p0.001).The clinical and angiographic outcomes of diabetic patients with BMS implantations were worse than those of patients without diabetes after a very long-term follow-up period.

Aim: The prognostic value of homocysteine (HCY) in patients with coronary artery diseases (CAD) is still controversial. The objective of this study was to investigate whether elevated HCY level at admission predict long-term outcomes in patients after percutaneous coronary interventions (PCI) with coronary artery stenting. Methods: From the institutional registry of Cardiovascular Atherosclerosis and Percutaneous TrAnsluminal INterventions (CAPTAIN), we enrolled a total of 1,307 patients with documented CAD undergone PCI with bare metal stents from July 2003 to December 2014. They were divided into two groups according to the fasting plasma HCY levels before catheterization: group I (883 patients, < 12 µmol/L) and group II (424 patients, ≥ 12 µmol/L). The primary endpoint was occurrence of major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, stroke, target lesion revascularization, new lesion stenting, and requiring bypass surgery. Results: After a mean follow-up period of 58 ± 41 months, the group II patients had a higher MACE rate (33.3% vs. 25.6%, p = 0.005). The main differences between two groups were cardiac death (8.0% vs. 3.4%, p = 0.001) and new lesion stenting (13.6% vs. 9.5%, p = 0.034). The risks of long-term MACE remained significantly higher in patients with elevated HCY level (≥ 12 µmol/L) after adjusting for clinical variables, with a hazard ratio of 1.29 (95% CI, 1.02–1.64, p = 0.036). Conclusions: Elevated HCY level (≥ 12 µmol/L) was independently associated with increased risk of long-term cardiovascular events in patients after coronary artery bare metal stents implantations. Thus, hyperhomocysteinemia may remain a useful prognostic marker for the risk assessment in clinical care of CAD patients.

BACKGROUND: Approximately one-third of cases of dilated cardiomyopathy (DCM) are caused by genetic mutations. With new sequencing technologies, numerous variants have been associated with this inherited cardiomyopathy, however the prevalence and genotype-phenotype correlations in different ethnic cohorts remain unclear. This study aimed to investigate the variants in Chinese DCM patients and correlate them with clinical presentations and prognosis. METHODS AND RESULTS: From September 2013 to December 2016, 70 index patients underwent DNA sequencing for 12 common disease-causing genes with next generation sequencing. Using a bioinformatics filtering process, 12 rare truncating variants (7 nonsense variants, 4 frameshift variants, and 1 splice site variant) and 29 rare missense variants were identified. Of these, 3 patients were double heterozygotes and 10 patients were compound heterozygotes. Overall, 47.1% (33/70) of the index patients had the seputatively pathogenic variants. The majority (33/41, 80.4%) of these variants were located in titin (TTN). More than 80% of the TTN variants (27/33, 81.8%) were distributed in the A band region of the sarcomere. Patients carrying these variants did not have a different phenotype in disease severity, clinical outcome and reversibility of ventricular function compared with non-carriers. CONCLUSIONS: Several new rare variants were identified in a Chinese population in this study, indicating that there are ethnic differences in genetic mutations in DCM patients. TTN remains the major disease-causing gene. Our results could be a reference for future genetic tests in Chinese populations. No specific genotype-phenotype correlations were found, however a prospective large cohort study may be needed to confirm our findings.

Massive blood transfusion (MBT) increased mortality and morbidity after cardiac surgery. However, a mid-term follow-up study on repair surgery of acute type A aortic dissection (AAAD) with MBT was lacking. This study aimed to assess the impact of perioperative MBT on late outcomes of surgical repair for AAAD. There were 3209 adult patients firstly received repair surgery for AAAD between 2005 and 2013, were identified using Taiwan National Health Insurance Research Database. Primary interest variable was MBT, defined as transfused red blood cell (RBC) ≥10 units. The outcomes contained in-hospital mortality, surgical-related complications, all-cause mortality, respiratory failure, and chronic kidney disease (CKD) during follow-up period. Higher in-hospital mortality (37.7% vs 11.6%; odds ratio, 4.00; 95% confidence interval [CI], 3.30–4.85), all-cause mortality (26.1% vs 13.0%; hazard ratio [HR], 1.66; 95% CI, 1.36–2.04), and perioperative complications were noted in the MBT group. A subdistribution hazard model revealed higher cumulative incidence of CKD (13.9% vs 6.5%; HR, 1.95; 95% CI, 1.47–2.60) and respiratory failure (7.1% vs 2.7%; HR, 2.34; 95% CI, 1.52–3.61) for the MBT cohort. A dose-dependent relationship between amount of transfused RBC (classified as tertiles) and cumulative incidence of all-cause mortality, incident CKD, and respiratory failure was found (P of trend test

Additional file 1: Figure S1. Study design. Figure S2. Summary of total reference numbers, disease distribution and sample type analysis of the miRNA candidates. Table S3. Kruskal–Wallis test and post hoc Dunn’s multiple comparisons of the 17 miRNAs among all groups (N = 108).

Compared to bare metal stent (BMS) implantation, drug-eluting stents (DES) is significantly better in attenuating intimal hyperplasia and reducing the rate of revascularization. However, the requirement of prolonged dual antiplatelet therapy (DAPT) and the economic cost have been the major disadvantages of DES. Studies have shown that the use of DES in small vessels decrease revascularization rate, but the results in large vessels vary. Previous studies have shown that the extent of late loss is unrelated to vessel diameter, and that late loss is easily accommodated in large vessels, thus resulting in decreased clinical benefit of DES in this setting. No definite cut-off point value of the vessel size has yet been demonstrated. Series studies aimed at evaluating the clinical outcomes of DES versus BMS in large vessels, but their results have been controversial. In this review, we evaluate the latest studies on clinical outcomes for different vessel sizes and clinical conditions. Nonetheless, further large clinical trials are warranted to address the clinical results of newer stents in different size vessels, especially in large vessels.

Introduction: This study aimed to evaluate the efficacy and safety of limus-based drug-eluting stent (DES) implanted in medium or small coronary vessels during a very long-term follow-up period. Methods: A total of 2383 patients treated with 2916 limus-based DES between April 2003 and March 2015 were evaluated. The enrolled patients were stratified into 3 groups according to the reference vessel diameter: group A: ≤2.5 mm; group B: 2.51 to 3.00 mm; group C: 3.01 to 3.50 mm. Results: Group A had a significantly higher loss index and binary restenosis rate than the other 2 groups at 9 months of angiographic follow-up. Group A also had a significantly higher rate of target lesion revascularization and a lower rate of major adverse cardiovascular event–free survival than the other 2 groups after a follow-up period of 68 ± 59 months. The long-term cardiovascular event–free survival curves based on a Cox regression model showed large vessel size, and second-generation DES had better outcomes. Conclusion: An inverse relationship between vessel size (≤3.5 mm) and clinical outcomes was noted in patients who received limus-based DES implantation.

Left ventricular diverticulum is a very rare entity to be found in adults. Noninvasive echocardiography can offer useful information prior to contrast-enhanced computer tomography or invasive angiography. We evaluated a patient with left ventricular apical diverticulum but complained no symptoms. Transthoracic echocardiography demonstrated a outpouching at left ventricle apex. A 640-slice computed tomography later confirmed the left ventricular diverticulum.

Background The optimal number of heartbeats required for representing left heart chamber function in patients with atrial fibrillation (AFib) has not been extensively studied. Methods To determine the optimal number, we performed an automated quantification analysis of three-dimensional echocardiography (3DE) data sets in 93 patients with AFib for whom 10–20 consecutive one-beat full-volume 3DE data sets were acquired twice. We measured left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and maximal left atrial volume (LAVmax) in each heartbeat; each parameter was averaged using a serial number of heartbeats randomly selected, and these values were compared with the averaged value obtained from the entire set of heartbeats. Coverage probability was determined using predefined cutoff values, the relative percentage differences in LVEDV and LAVmax of 5%, and the absolute percentage differences in LVEF of 5%. The optimal number of heartbeats was defined as the minimum number of heartbeats showing coverage probability ≥95%. Results Out of 93 patients, 73 patients had acceptable left ventricular contour casts (feasibility, 78%), and 79 patients had acceptable left atrial contour casts (feasibility, 85%). Using the aforementioned criteria, the minimum optimal number of heartbeats was nine for LVEDV and six for LAVmax. The corresponding minimum optimal number of heartbeats for LVEF was eight. However, the results varied as a function of the size of the chamber, the left ventricular function, and whether the AFib ventricular rate was controlled. Conclusions In patients with AFib, the optimal number of heartbeats required to obtain representative chamber volumes and function was six to nine heartbeats randomly selected using 3DE automated quantification software.

The circadian rhythm regulates blood pressure and maintains fluid and electrolyte homeostasis with central and peripheral clock. However, the role of circadian rhythm in the pathogenesis of tubulointerstitial fibrosis remains unclear. Here, we found that the amplitudes of circadian rhythm oscillation in kidneys significantly increased after unilateral ureteral obstruction. In mice that are deficient in the circadian gene Clock, renal fibrosis and renal parenchymal damage were significantly worse after ureteral obstruction. CLOCK-deficient mice showed increased synthesis of collagen, increased oxidative stress, and greater transforming growth factor-β (TGF-β) expression. TGF-β mRNA expression oscillated with the circadian rhythms under the control of CLOCK-BMAL1 heterodimers. The expression of cyclooxygenase 2 was significantly higher in kidneys from CLOCK-deficient mice with ureteral obstruction. Treatment with a cyclooxygenase 2 inhibitor celecoxib significantly improved renal fibrosis in CLOCK-deficient mice. Taken together, these data establish the importance of the circadian rhythm in tubulointerstitial fibrosis and suggest CLOCK/TGF-β signaling as a novel therapeutic target of cyclooxygenase inhibition.