Interspecies/Intergroup Complementation of Orthotospovirus Replication and Movement through Reverse Genetics Systems.

Orthotospoviruses, the plant-infecting bunyaviruses, cause serious diseases in agronomic crops and pose major threats to global food security. The family of Tospoviridae contains more than 30 members that are classified into two geographic groups, American-type and Euro/Asian-type orthotospovirus. However, the genetic interaction between different species and the possibility, during mixed infections, for transcomplementation of gene functions by orthotospoviruses from different geographic groups remains underexplored. In this study, minireplicon-based reverse genetics (RG) systems have been established for Impatiens necrotic spot virus (INSV) (an American-type orthotospovirus) and for Calla lily chlorotic spot virus and Tomato zonate spot virus (CCSV and TZSV) (two representative Euro/Asian orthotospoviruses). Together with the earlier established RG system for Tomato spotted wilt virus (TSWV), a type species of the Orthotospovirus American-clade, viral replicase/movement proteins were exchanged and analyzed on interspecies transcomplementation. Whereas the homologous RNA-dependent RNA polymerase (RdRp) and nucleocapsid (N) protein supported the replication of orthotospoviruses from both geographic groups, heterologous combinations of RdRp from one group and N from the other group were unable to support the replication of viruses from both groups. Furthermore, the NSm movement protein (MP), from both geographic groups of orthotospoviruses, was able to transcomplement heterologous orthotospoviruses or a positive-strand Cucumber mosaic virus (CMV) in their movement, albeit with varying efficiency. MP from Rice stripe tenuivirus (RSV), a plant-infecting bunyavirus that is distinct from orthotospoviruses, or MP from CMV also moves orthotospoviruses. Our findings gain insights into the genetic interaction/reassortant potentials for the segmented plant orthotospoviruses. IMPORTANCE Orthotospoviruses are agriculturally important negative-strand RNA viruses and cause severe yield-losses on many crops worldwide. Whereas the emergence of new animal-infecting bunyaviruses is frequently associated with genetic reassortants, this issue remains underexposed with the plant-infecting orthotospovirus. With the development of reverse genetics systems for orthotospoviruses from different geographic regions, the interspecies/intergroup replication/movement complementation between American- and Euro/Asian-type orthotospoviruses were investigated. Genomic RNAs from American orthotospoviruses can be replicated by the RdRp and N from those of Euro/Asia-group orthotospoviruses, and vice versa. However, their genomic RNAs cannot be replicated by a heterologous combination of RdRp from one geographic group and N from another geographic group. Cell-to-cell movement of viral entity is supported by NSm from both geographic groups, with highest efficiency by NSm from viruses belonging to the same group. Our findings provide important insights into the genetic interaction and exchange ability of viral gene functions between different species of orthotospovirus.

Alteration of the gut microbiome in patients with heart failure: A systematic review and meta-analysis.

Recent research has revealed that alterations of the gut microbiome (GM) play a comprehensive role in the pathophysiology of HF. However, findings in this field remain controversial. In this study, we focus on differences in GM diversity and abundance between HF patients and non-HF people, based on previous 16 S ribosomal RNA (16rRNA) gene sequencing. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a comprehensive search of PubMed, Web of Science, Embase, Cochrane Library, and Ovid databases using the keyword "Heart failure" and "Gastrointestinal Microbiome". A significant decrease in alpha diversity was observed in the HF patients (Chao1, I2 = 87.5 %, p < 0.001; Shannon index, I2 = 62.8 %, p = 0.021). At the phylum level, the HF group exhibited higher abundances of Proteobacteria (I2 = 92.0 %, p = 0.004) and Actinobacteria (I2 = 82.5 %, p = 0.010), while Bacteroidetes (I2 = 45.1 %, p = 0.017) and F/B ratio (I2 = 0.0 %, p＜0.001) were lower. The Firmicutes showed a decreasing trend but did not reach statistical significance (I2 = 82.3 %, p = 0.127). At the genus level, the relative abundances of Streptococcus, Bacteroides, Alistipes, Bifidobacterium, Escherichia-Shigella, Enterococcus and Klebsiella were increased in the HF group, whereas Ruminococcus, Faecalibacterium, Dorea and Megamona exhibited decreased relative abundances. Dialister, Blautia and Prevotella showed decreasing trends but without statistical significance. This observational meta-analysis suggests that GM changes are associated with HF, manifesting as alterations in GM abundance, disruptions in the production of short-chain fatty acids (SCFAs) bacteria, and an increase in trimethylamine N-oxide (TMAO) producing bacteria.

Percutaneous left atrial appendage closure with SeaLA device in non-valvular atrial fibrillation.

OBJECTIVES: The clinical efficacy and safety of a novel left atrial appendage (LAA) occluder of the SeaLA closure system in patients with nonvalvular atrial fibrillation (NVAF) were reported. BACKGROUND: Patients with NVAF are at a higher risk of stroke compared to healthy individuals. Left atrial appendage closure (LAAC) has emerged as a prominent strategy for reducing the risk of thrombosis in individuals with NVAF. METHODS: A prospective, multicenter study was conducted in NVAF patients with a high risk of stroke. RESULTS: The LAAC was successfully performed in 163 patients. The mean age was 66.93 ± 7.92 years, with a mean preoperative CHA2DS2-VASc score of 4.17 ± 1.48. One patient with residual flow >3 mm was observed at the 6-month follow-up, confirmed by TEE. During the follow-up, 2 severe pericardiac effusions were noted, and 2 ischemic strokes were observed. Four device-related thromboses were resolved after anticoagulation treatment. There was no device embolism. CONCLUSIONS: The LAAC with the SeaLA device demonstrates encouraging feasibility, safety, and efficacy outcomes.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society .

Anticoagulation Intensity during Appendage Occlusion:Lessons from Silent Cerebral Embolism.

INTRODUCTION: Endovascular left atrial appendage occlusion (LAAO) is associated with a high incidence of peri-procedure silent cerebral embolisms (SCE), while the recommended activated clotting time (ACT) level by the expert consensus is lower than that in atrial fibrillation (AF) ablation. The aim of our study is to investigate whether raising the targeted ACT level during LAAO to the same level as AF ablation could decrease the incidence of SCE. METHODS: It was a prospective observational cohort study. Consecutive AF patients receiving LAAO between January 2021 and December 2022 were included and categorized into two groups based on the time of enrollment. Patients enrolled in 2021 (group 250) maintained a target ACT level of ≥250 s during LAAO procedure, while patients enrolled in 2022 (group 300) maintained the peri-procedure ACT ≥300 s. All patients underwent cerebral magnetic resonance imaging (MRI) before and after the procedure. RESULTS: A total of 81 patients were included (38 in the group 250 and 43 in the group 300). After inverse probability of treatment weighting (IPTW), patients in the group 250 showed a significantly lower incidence of SCE than group 300 (IPTW p = 0.038). Only a stable high ACT pattern could decrease the risk of SCE. No significant differences were found between other ACT change patterns on the SCE incidence. CONCLUSION: Raising the peri-procedure ACT level to a stable 300 seconds could decrease the risk of the SCE without increasing the major bleeding events.

Catheter ablation versus antiarrhythmic drug therapy for sustained ventricular tachycardia in patients with hypertrophic cardiomyopathy.

BACKGROUND: Ventricular tachycardia (VT) is the primary cause of sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, the strategy for VT treatment in HCM patients remains unclear. This study is aimed to compare the effectiveness of catheter ablation versus antiarrhythmic drug (AAD) therapy for sustained VT in patients with HCM. METHODS: A total of 28 HCM patients with sustained VT at 4 different centers between December 2012 and December 2021 were enrolled. Twelve underwent catheter ablation (ablation group) and sixteen received AAD therapy (AAD group). The primary outcome was VT recurrence during follow-up. RESULTS: Baseline characteristics were comparable between two groups. After a mean follow-up of 31.4 ± 17.5 months, the primary outcome occurred in 35.7% of the ablation group and 90.6% of the AAD group (hazard ratio [HR], 0.29 [95%CI, 0.10-0.89]; P = 0.021). No differences in hospital admission due to cardiovascular cause (25.0% vs. 71.0%; P = 0.138) and cardiovascular cause-related mortality/heart transplantation (9.1% vs. 50.6%; P = 0.551) were observed. However, there was a significant reduction in the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation in ablation group as compared to that of AAD group (42.9% vs. 93.7%; HR, 0.34 [95% CI, 0.12-0.95]; P = 0.029). CONCLUSIONS: In HCM patients with sustained VT, catheter ablation reduced the VT recurrence, and the composite endpoint of VT recurrence, hospital admission due to cardiovascular cause, cardiovascular cause-related mortality, or heart transplantation as compared to AAD.

Mid-term outcome of catheter ablation of idiopathic non-outflow tract ventricular arrhythmias.

BACKGROUND: Catheter ablation is recommended in patients with frequent and symptomatic ventricular arrhythmias (VAs) in an otherwise normal heart. Right or left outflow tract (OT) are the most common origins, and catheter ablation is highly effective with low complication rates. However, outcome of catheter ablation of VAs other than the OT (non-OTVAs) is limited. The aim of this single-center study was to assess the safety and mid-term outcome of catheter ablation for non-OTVAs. METHOD AND RESULTS: From 2013 to 2018, 251 patients who underwent catheter ablation for idiopathic non-OTVAs were enrolled and grouped according to the origins including His-Purkinje system (HPS, n = 108), papillary muscle / moderator band (PM/MB, n = 47), tricuspid annulus (TA, n = 70), and mitral annulus (MA, n = 26), 244 (97.2%) had acute elimination of VAs. The time of VAs recurrence of the single procedure was 1.69 (0.12,9.72) months, with 66% occurring within the first 3 months. The recurrence rate was significantly higher in the PM/MB group than in the TA (p = 0.025) and MA groups (p = 0.023). The single procedure success rate in all patients was 70.1%, in which 66.7%, 59.6%, 80%, and 76.9% were achieved in the HPS, PM/MB, TA, and MA groups, respectively (p = 0.284). After multiple procedures, the total success rate was 76.5% at the follow-up of 4.38 ± 2.42 years. The rate was significantly lower in the PM/MB group than in the TA group (p = 0.035). In subgroup analysis, no significant difference was observed in the recurrence rate of single procedure in patients with different VA origins within the PM/MB (log-rank test, p = 0.546). CONCLUSION: Despite a certain percentage of recurrences observed in the mid-term follow-up, catheter ablation remained feasible and effective for idiopathic non-OTVAs.

Value of q waves in lateral and left precordial leads in patients with left bundle branch block to predict the response to cardiac resynchronization therapy.

BACKGROUND: The cardiac resynchronization therapy (CRT) non-response rate can reach 30% in heart failure (HF) patients with left bundle branch block (LBBB). This study aimed to evaluate the value of baseline q waves in leads I, V5, or V6 in predicting response to CRT in patients with HF and LBBB. METHODS: Patients with HF (left ventricular ejection fraction ≤35%) and LBBB receiving CRT implantation were retrospectively enrolled. Baseline characteristics and electrocardiogram parameters, including lateral and left precordial q waves were evaluated. Non-response to CRT was defined as the improvement of left ventricular ejection fraction (LVEF) < 5% at a 6-month follow-up. RESULTS: A total of 132 patients (mean age 63.0 ± 10.4 years, 94 [71.2%] male) were included. Among them, 32 patients with q waves in leads I, V5, or V6 were classified into the qLBBB (+) group, and the rest without q waves in these leads were defined as the qLBBB (-) group. The CRT non-response rate in the qLBBB (+) group was markedly higher than that in the qLBBB (-) group (68.8% vs. 33.3%, p < .001). Multivariable logistic regression analysis revealed that the presence of baseline q waves in leads I, V5, or V6 remained significantly associated with a higher rate of CRT non-response in patients with HF and LBBB (odds ratio: 4.8, 95% confidence interval: 1.5-15.0, p = .007). CONCLUSION: Any q wave in leads I, V5, or V6 was an independent predictive factor for CRT non-response in patients with HF and LBBB.

Deep terminal negative of the P wave in V1 and incidence of ischemic stroke: The atherosclerosis risk in communities (ARIC) study.

BACKGROUND: Deep terminal negative of the P wave in V1 (DTNPV1) is a marker of left atrial remodeling. We aimed to evaluate the association of DTNPV1 with incident ischemic stroke. METHODS: The Atherosclerosis Risk in Communities study is a prospective community-based cohort study. All participants at visit 4 (1996-1998) except those with prevalent stroke, missing covariates, and missing or uninterpretable ECG were included. DTNPV1 was defined as the absolute value of the depth of the terminal negative phase >100 µV in the presence of biphasic P wave in V1. Association between DTNPV1 as a time-dependent exposure variable and incident ischemic stroke was evaluated. The accuracy of the prediction model consisting of DTNPV1 and CHA2DS2-VASc variables in predicting ischemic stroke was analyzed. RESULTS: Among 10,605 participants (63 ± 6 years, 56% women, 20% Black), 803 cases of ischemic stroke occurred over a median follow-up of 20.19 years. After adjusting for demographics, DTNPV1 was associated with an increased risk of stroke (HR 1.96, [95% CI 1.39-2.77]). After further adjusting for stroke risk factors, use of aspirin and anticoagulants, and time-dependent atrial fibrillation, DTNPV1 was associated with a 1.50-fold (95% CI 1.06-2.13) increased risk of stroke. When added to the CHA2DS2-VASc variables, DTNPV1 did not significantly improve stroke prediction as assessed by C-statistic. However, there was improvement in risk classification for participants who did not develop stroke. CONCLUSION: DTNPV1 is significantly associated with higher risk of ischemic stroke. Since DTNPV1 is a simplified electrocardiographic parameter, it may help stroke prediction, a subject for further research.

First-Line Catheter Ablation of Monomorphic Ventricular Tachycardia in Cardiomyopathy Concurrent With Defibrillator Implantation: The PAUSE-SCD Randomized Trial.

BACKGROUND: Catheter ablation as first-line therapy for ventricular tachycardia (VT) at the time of implantable cardioverter defibrillator (ICD) implantation has not been adopted into clinical guidelines. Also, there is an unmet clinical need to prospectively examine the role of VT ablation in patients with nonischemic cardiomyopathy, an increasingly prevalent population that is referred for advanced therapies globally. METHODS: We conducted an international, multicenter, randomized controlled trial enrolling 180 patients with cardiomyopathy and monomorphic VT with an indication for ICD implantation to assess the role of early, first-line ablation therapy. A total of 121 patients were randomly assigned (1:1) to ablation plus an ICD versus conventional medical therapy plus an ICD. Patients who refused ICD (n=47) were followed in a prospective registry after stand-alone ablation treatment. The primary outcome was a composite end point of VT recurrence, cardiovascular hospitalization, or death. RESULTS: Randomly assigned patients had a mean age of 55 years (interquartile range, 46-64) and left ventricular ejection fraction of 40% (interquartile range, 30%-49%); 81% were male. The underlying heart disease was ischemic cardiomyopathy in 35%, nonischemic cardiomyopathy in 30%, and arrhythmogenic cardiomyopathy in 35%. Ablation was performed a median of 2 days before ICD implantation (interquartile range, 5 days before to 14 days after). At 31 months, the primary outcome occurred in 49.3% of the ablation group and 65.5% in the control group (hazard ratio, 0.58 [95% CI, 0.35-0.96]; P=0.04). The observed difference was driven by a reduction in VT recurrence in the ablation arm (hazard ratio, 0.51 [95%CI, 0.29-0.90]; P=0.02). A statistically significant reduction in both ICD shocks (10.0% versus 24.6%; P=0.03) and antitachycardia pacing (16.2% versus 32.8%; P=0.04) was observed in patients who underwent ablation compared with control. No differences in cardiovascular hospitalization (32.0% versus. 33.7%; hazard ratio, 0.82 [95% CI, 0.43-1.56]; P=0.55) or mortality (8.9% versus 8.8%; hazard ratio, 1.40 [95% CI, 0.38-5.22]; P=0.62]) were observed. Ablation-related complications occurred in 8.3% of patients. CONCLUSIONS: Among patients with cardiomyopathy of varied causes, early catheter ablation performed at the time of ICD implantation significantly reduced the composite primary outcome of VT recurrence, cardiovascular hospitalization, or death. These findings were driven by a reduction in ICD therapies. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02848781.

Self-Amplified Cascade Degradation and Oxidative Stress Via Rational pH Regulation of Oxidation-Responsive Poly(ferrocene) Aggregates.

Precise activation of polymer nanoparticles at lesion sites is crucial to achieve favorable therapeutic efficacy. However, conventional endogenous stimuli-responsive polymer nanoparticles probably suffer from few triggers to stimulate the polymer degradation and subsequent functions. Here, we describe oxidation-responsive poly(ferrocene) amphiphiles containing phenylboronic acid ester and ferrocene as the repeating backbone units. Upon triggering by hydrogen peroxide inside the tumor cells, the phenylboronic acid ester bonds are broken and poly(ferrocene) units are degraded to afford free ferrocene and noticeable hydroxide ions. The released hydroxide ions can immediately improve the pH value within the poly(ferrocene) aggregates, and the degradation rate of the phenylboronic acid ester backbone is further promoted by the upregulated pH; thereupon, the accelerated degradation can release much more additional hydroxide ions to improve the pH, thus achieving a positive self-amplified cascade degradation of poly(ferrocene) aggregates accompanied by oxidative stress boosting and efficient cargo release. Specifically, the poly(ferrocene) aggregates can be degraded up to ∼90% within 12 h when triggered by H2O2, while ferrocene-free control nanoparticles are degraded by only 30% within 12 days. In addition, the maleimide moieties tethered in the hydrophilic corona can capture blood albumin to form an albumin-rich protein corona and significantly improve favorable tumor accumulation. The current oxidation-responsive poly(ferrocene) amphiphiles can efficiently inhibit tumors in vitro and in vivo. This work provides a proof-of-concept paradigm for self-amplified polymer degradation and concurrent oxidative stress, which is promising in actively regulated precision medicine.

Label-Free Quantification of Digital Nanorods Assembled from Discrete Oligourethane Amphiphiles.

Polymeric nanoparticles (NPs) have been extensively designed for theranostic agent delivery. Previous methods for tracking their biological behavior and assessing theranostic efficacy heavily rely on fluorescence or isotope labeling. However, these labeling techniques may alter the physicochemical properties of the labeled NPs, leading to inaccurate biodistribution information. Therefore, it is highly desirable to develop label-free techniques for accurately assessing the biological fate of polymeric NPs. Here, we create discrete oligourethane amphiphiles (DOAs) with methoxy (OMe), hydroxyl (OH), and maleimide (MI) moieties at the dendritic oligo(ethylene glycol) (dOEG) ends. We obtained four types of digital nanorods (NRs) with distinct surface functional groups through self-assembly of a single DOA (OMe and OH NRs) or coassembly of two DOAs (OMe-MI and OH-MI NRs). These unique NRs can be directly quantified in a label-free manner by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Specifically, OMe-MI NRs exhibited the best blood circulation, and OH-MI showed the highest area under the curve (AUC) value after intravenous injection. Biodistribution studies demonstrated that MI-containing NRs generally had lower accumulation in the liver and spleen compared to that of MI-free NRs, except for the comparison between OMe and OMe-MI NRs in the liver. Proteomics studies unveiled the formation of distinct protein coronas that may greatly affect the biological behavior of NRs. This study not only provides a label-free technique for quantifying the pharmacokinetics and biodistribution of polymeric NRs but also highlights the significant impact of surface functional groups on the biological fate of polymeric NPs.

Early onset atrial lesions in a patient with a novel LMNA frameshift mutation.

Genetic mutations in the lamin A/C gene (LMNA) have been linked to cardiomyopathy. Different mutational sites exhibit different clinical manifestations and prognoses. Herein, we identified a novel LMNA frameshift mutation, p.P485Tfs*67, from a patient with early-onset atrial disease. To verify the pathogenicity of this variation, a transgenic zebrafish model was constructed, which demonstrated that adult zebrafish with the LMNA mutation showed an abnormal ECG and impaired myocardial structure. Our study suggests the atrial pathogenicity of the LMNA-P485Tfs mutation, which is helpful to understand the function of the Ig-like domain of lamin A/C.

Targeted Nanodrugs to Destroy the Tumor Extracellular Matrix Barrier for Improving Drug Delivery and Cancer Therapeutic Efficacy.

One of the main reasons why most cancer patients do not respond well to chemotherapy is that drugs cannot accumulate in tumors at an optimal dose, eventually resulting in failure to prevent cancer cell growth. To improve drug delivery efficiency, we engineered a highly efficient tumor-targeted and stroma-breaking nanocarrier by the modification of iron oxide nanoparticles (IONPs) with a tumor-targeting peptide c(RGDyK) and a hyaluronidase (HAase) on the surface. The yielding nanocomplex, c(RGDyK)-HAase-IONP, targeted the tumor by binding integrin αvß3 and went deeply into the tumors by the degradation of hyaluronic acid (HA), which was highly expressed in the tumor extracellular matrix (ECM). Good biostability and a low pH preferred drug release profile were characterized for c(RGDyK)-HAase-IONP carrying DOX in vitro. c(RGDyK)-HAase-IONP showed an improved tumor-targeting (2.5 times higher) effect after intravenous injection in the MC38 tumor-bearing mice model, as determined by whole-body fluorescence imaging compared to the non-targeted IONPs without HAase. After 5 systemic treatments, c(RGDyK)-HAase-IONP/DOX (5 mg/kg of equivalent dose of DOX) significantly inhibited MC38 tumor growth (22.1 ± 7.4 times relative to the non-treated group). Elevated apoptosis and reduced proliferation in the tumor cell were detected in the c(RGDyK)-HAase-IONP/DOX treated tumors compared to the control groups. Overall, the highly efficient targeted nanocarrier c(RGDyK)-HAase-IONP demonstrated tremendous potency for improving drug delivery and tumor therapy efficacy by targeted degradation of the dense HA barrier in the tumor ECM. We determined that such a tumor stroma-degrading nanosystem was capable of reducing tumor recurrence and drug resistance and could ultimately improve clinical tumor treatment responses.

Texture analysis of SPECT myocardial perfusion provides prognostic value for dilated cardiomyopathy.

BACKGROUND: Texture analysis (TA) has demonstrated clinical values in extracting information, quantifying inhomogeneity, evaluating treatment outcomes, and predicting long-term prognosis for cardiac diseases. The aim of this study was to explore whether TA of SPECT myocardial perfusion could contribute to improving the prognosis of dilated cardiomyopathy (DCM) patients. METHODS: Eighty-eight patients were recruited in our study between 2009 and 2020 who were diagnosed with DCM and underwent single-photon emission tomography myocardial perfusion imaging (SPECT MPI). Forty TA features were obtained from quantitative analysis of SPECT imaging in subjects with myocardial perfusion at rest. All patients were divided into two groups: the all-cause death group and the survival group. The prognostic value of texture parameters was assessed by Cox regression and Kaplan-Meier analysis. RESULTS: Twenty-five all-cause deaths (28.4%) were observed during the follow-up (39.2±28.7 months). Compared with the survival group, NT-proBNP and total perfusion deficit (TPD) were higher and left ventricular ejection fraction (LVEF) was lower in the all-cause death group. In addition, 26 out of 40 texture parameters were significantly different between the two groups. Univariate Cox regression analysis revealed that NT-proBNP, LVEF, and 25 texture parameters were significantly associated with all-cause death. The multivariate Cox regression analysis showed that low gray-level emphasis (LGLE) (P = 0.010, HR = 4.698, 95% CI 1.457-15.145) and long-run low gray-level emphasis (LRLGE) (P =0.002, HR = 6.085, 95% CI 1.906-19.422) were independent predictors of the survival outcome. When added to clinical parameters, LVEF, TPD, and TA parameters, including LGLE and LRLGE, were incrementally associated with all-cause death (global chi-square statistic of 26.246 vs. 33.521; P = 0.028, global chi-square statistic of 26.246 vs. 34.711; P = 0.004). CONCLUSION: TA based on gated SPECT MPI could discover independent prognostic predictors of all-cause death in medically treated patients with DCM. Moreover, TA parameters, including LGLE and LRLGE, independent of the total perfusion deficit of the cardiac myocardium, appeared to provide incremental prognostic value for DCM patients.

Arrhythmogenesis of surgical atrial incisions and lesions in Maze procedure: insights from high-resolution mapping of atrial tachycardias.

BACKGROUND: Atrial tachycardias (ATs) frequently develop after a surgical Maze procedure. We aimed to elucidate the electrophysiologic mechanisms and their arrhythmogenic substrates of these ATs. METHODS AND RESULTS: We retrospectively reviewed 20 patients (14 females, mean age of 55.5 ± 8.6 years) with post-Maze ATs who underwent high-resolution mapping at three institutions. The slow conduction areas, reentry circuits, voltage signals, complex electrograms, and their correlation with the surgical incisions and lesions placed in the surgical Maze procedures were analyzed. Thirty-six ATs with a mean cycle length of 260.0 ± 67.6 ms were mapped in these patients. Among them, 22 (61.1%) were anatomical macro-reentrant ATs (AMAT), 12 (33.3%) non-AMATs (localized ATs), and 2 (5.6%) focal ATs, respectively. Epicardial conduction bridges were observed in 6/20 (30.0%) patients and 7/36 (19.4%) ATs. Different arrhythmogenic substrates were identified in these ATs, including slow conduction regions within the previous lesion areas or between the incisions and anatomical structures, the prolonged activation pathways caused by the short lesions connecting the tricuspid annulus, and the circuits around the long incisions and/or lesions. CONCLUSIONS: Reentry is the main mechanism of the post-Maze ATs. The pro-arrhythmic substrates are most likely caused by surgical incisions and lesions. The slow conduction regions and the protected channels yielded from these areas are the major arrhythmogenic factors.

Plasma 8-Hydroxy-2'-Deoxyguanosine, a Potential Valuable Biomarker for Atrial Fibrosis Is Influenced by Polymorphism of DNA Methylation Gene.

BACKGROUND: Previous studies revealed a relationship between 8-hydroxy-2'-deoxyguanosine (8-OHdG) and the occurrence/recurrence of atrial fibrillation (AF). This 2-part study aimed to validate whether DNA damage related to 8-OHdG is associated with left atrial (LA) fibrosis in AF patients quantified by voltage mapping (Part I), and to identify the underlying genetic components regulating the 8-OHdG level (Part II).Methods and Results: Plasma 8-OHdG determination, DNA extraction, and genotyping were conducted before catheter ablation. LA voltage mapping was performed under sinus rhythm. According to the percentage of low voltage area (LVA), patients were categorized as stage I (<5%), stage II (5-10%), stage III (10-20%), and stage IV (>20%). Part I included 209 AF patients. The 8-OHdG level showed an upward trend together with advanced LVA stage (stage I 8.1 [6.1, 10.5] ng/mL, stage II 8.5 [5.7, 14.1] ng/mL, stage III 14.3 [12.1, 16.5] ng/mL, stage IV 13.9 [10.5, 16.0] ng/mL, P<0.000). Part II included 175 of the 209 patients from Part I. Gene-set analysis based on genome-wide association study summary data identified that the gene set named 'DNA methylation on cytosine' was the only genetic component significantly associated with 8-OHdG concentration. CONCLUSIONS: Higher 8-OHdG levels may predict more advanced LVA of the LA in AF patients. DNA methylation is the putative genetic component underlying oxidative DNA damage in AF patients.

Frequency of prothrombin time-international normalized ratio monitoring and the long-term prognosis in patients with mechanical valve replacement.

BACKGROUND: The study aimed to assess the correlation between the monitoring frequency of PT-INR and the long-term prognosis in patients with mechanical heart valve (MHV) replacement after discharge. METHODS: This single-center, observational study enrolled patients who underwent MHV replacement and discharged from June 2015 to May 2018. Patients or their corresponding family members were followed with a telephone questionnaire survey in July-October 2020. Based on monitoring intervals, patients were divided into frequent monitoring (FM) group (≤ 1 month) and less frequent monitoring (LFM) group (> 1 month). The primary endpoint was the composite of thromboembolic event, major bleeding or all-cause death. The secondary endpoints were thromboembolic event, major bleeding or all-cause death, respectively. RESULTS: A total of 188 patients were included in the final analysis. The median follow-up duration was 3.6 years (Interquartile range: 2.6 to 4.4 years). 104 (55.3%) patients and 84 (44.7%) patients were classified into the FM group and the LFM group, respectively. The FM group had a significantly lower incidence of the primary endpoint than the LFM group (3.74 vs. 1.16 per 100 patient-years, adjusted HR: 3.31 [95% CI 1.05-10.42, P = 0.041]). Secondary analysis revealed that the risk of thromboembolic events and all-cause death were also reduced in the FM group. CONCLUSIONS: The management of warfarin treatment in patients after MHV replacement remains challenging. Patients with less frequent monitoring of PT-INR might have worse clinical prognosis than those with frequent PT-INR monitoring.

Scar-related atrial macroreentries: Different arrhymogenic basis generates different reentry type.

BACKGROUND: Catheter ablation is an established therapeutic strategy to treat scar-related macroreentry atrial tachycardia (MAT). However, the scar properties and arrhythmogenicity and the reentry type have not been clearly defined. METHODS AND RESULTS: A total of 122 patients with scar-related MAT were enrolled in this study. The atrial scars were classified into two categories: spontaneous scars (Group A: n = 28) and iatrogenic scars (Group B: n = 94). According to the relationship between scar location and the reentry circuit, MAT was described as scar pro-flutter MAT, scar-dependent MAT, and scar-mediated MAT. The reentry type of MAT was significantly different between Groups A and B: pro-flutter (40.5% vs. 62.0%, p = 0.02), scar-dependent AT (40.5% vs. 13.0%, p < 0.001), and scar-mediated AT (19.0% vs. 25.0%, p = 0.42). After a median follow-up of 25 months, 21 patients with AT recurrence were observed. Compared with the spontaneous group, there was a lower recurrence rate of MAT in the iatrogenic group (28.6% vs. 10.6%, p = 0.03). CONCLUSION: Scar-related MAT has three reentry types, and the proportion of each type varies with the scar properties and its arrhythmogenic basis. Optimization of the ablation strategy based on the scar properties to improve the long-term outcome of catheter ablation of MAT is necessary.

Persistent left superior vena cava isolation in patients with atrial fibrillation: Selective or empirical?

BACKGROUND: Persistent left superior vena cava (PLSVC) is the most prevalent form of thoracic venous abnormality and can serve as a significant arrhythmogenic source in atrial fibrillation (AF). METHODS AND RESULTS: Among the 3950 patients who underwent radiofrequency ablation for AF between September 2014 to April 2020, 17 patients (mean age 59.4 ± 8.0 years, 64.7% male) with PLSVC were identified. Among them, nine patients (52.9%) had a prior history of pulmonary vein isolation (PVI) alone. Eight out of nine patients who experienced AF recurrence underwent PLSVC isolation with or without pulmonary vein (PV) reconnection. For the remaining eight patients (47.1%), PVI plus PLSVC isolation were performed during the index procedure. Ectopy originating from PLSVC was documented in 11 patients (64.7%) and successful PLSVC isolation was achieved in 16 patients (94.1%). After a median follow-up of 28.3 months, freedom from AF/ atrial tachycardia (AT) was observed in 13 patients (76.5%). CONCLUSION: Empirical PLSVC isolation beyond PVI appears to be a feasible and safe strategy to prevent AF recurrence in patients with concomitant PLSVC.