Serum electrolyte concentrations and risk of atrial fibrillation: an observational and mendelian randomization study.

BACKGROUND: Atrial fibrillation (AF) is a prevalent arrhythmic condition resulting in increased stroke risk and is associated with high mortality. Electrolyte imbalance can increase the risk of AF, where the relationship between AF and serum electrolytes remains unclear. METHODS: A total of 15,792 individuals were included in the observational study, with incident AF ascertainment in the Atherosclerosis Risk in Communities (ARIC) study. The Cox regression models were applied to calculate the hazard ratio (HR) and 95% confidence interval (CI) for AF based on different serum electrolyte levels. Mendelian randomization (MR) analyses were performed to examine the causal association. RESULTS: In observational study, after a median 19.7 years of follow-up, a total of 2551 developed AF. After full adjustment, participants with serum potassium below the 5th percentile had a higher risk of AF relative to participants in the middle quintile. Serum magnesium was also inversely associated with the risk of AF. An increased incidence of AF was identified in individuals with higher serum phosphate percentiles. Serum calcium levels were not related to AF risk. Moreover, MR analysis indicated that genetically predicted serum electrolyte levels were not causally associated with AF risk. The odds ratio for AF were 0.999 for potassium, 1.044 for magnesium, 0.728 for phosphate, and 0.979 for calcium, respectively. CONCLUSIONS: Serum electrolyte disorders such as hypokalemia, hypomagnesemia and hyperphosphatemia were associated with an increased risk of AF and may also serve to be prognostic factors. However, the present study did not support serum electrolytes as causal mediators for AF development.

Efficacy of ablation index-guided pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Ablation index (AI) is a novel technology of ablation lesion quality to help improve homogeneity of lesion size and continuity. In this study, we aim to evaluate whether AI-guided PVI improves clinical outcomes compared to CF-guided PVI in patients with paroxysmal AF (PAF). METHODS: Patients undergoing first-time radiofrequency ablation for PAF were randomized in a 2:1 ratio to two groups: AI-guided PVI and CF-guided PVI. In the AI group, AI ≥500 was recommended at the anterior/superior/inferior walls, 350-400 at the posterior wall, and inter-lesion distance ≤4 mm. The primary endpoint is the freedom from atrial arrhythmia recurrence during 12 months follow-up, without antiarrhythmic drug therapy (ADT). The key secondary endpoints include intra-procedural efficiency and peri-procedural complications. RESULTS: Two hundred twenty five patients were randomized (AI group [n = 149] and CF group [n = 76]). First-pass isolation rate in AI group was significantly higher than that in CF group (58.3% vs. 43.4%, p = .035). After a median follow-up of 12.2 months, 154/225 (68.4%) of patients were free from atrial arrhythmia recurrence without ADT, which was higher in AI group compared with CF group, but without significant difference (71.1% vs. 63.2%, p = .253). The incidence of peri-procedural complications is low and without difference between two groups. CONCLUSIONS: AI-guided ablation provided higher acute efficacy than CF-guided ablation in PV isolation for patients with paroxysmal AF. The long-term success rate in AI group was higher than CF group, but did not reach statistical significance.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Electrophysiological characteristics of epicardial to endocardial breakthrough in intractable cavotricuspid isthmus-dependent atrial flutter.

BACKGROUND: Epicardial to endocardial breakthrough (EEB) exists widely in atrial arrhythmia and is a cause for intractable cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL). This study aimed to investigate the electrophysiological features of EEB in EEB-related CTI dependent AFL. METHODS: Six patients with EEB-related CTI-dependent AFL were identified among 142 consecutive patients who underwent CTI-dependent AFL catheter ablation with an ultra-high-density, high-resolution mapping system in three institutions. Activation maps and ablation procedure were analyzed. RESULTS: A total of seven EEBs were found in six patients. Four EEBs (including three at the right atrial septum and one in paraseptal isthmus) were recorded in three patients during tachycardia. The other three EEBs were identified at the inferolateral right atrium (RA) during pacing from the coronary sinus. The conduction characteristics through the EEB-mediated structures were evaluated in three patients. Two patients only showed unidirectional conduction. Activation maps indicated that CTI-dependent AFL with EEB at the atrial septum was actually bi-atrial macro-reentrant atrial tachycardia (BiAT). Intensive ablation at the central isthmus could block CTI bidirectionally in four cases. However, ablation targeted at the inferolateral RA EEB was required in two cases. Meanwhile, local potentials at the EEB location gradually split into two components with a change in activation sequence. CONCLUSIONS: EEB is an underlying cause for intractable CTI-dependent AFL. EEB-mediated structure might show unidirectional conduction. CTI-dependent AFL with EEB at the atrial septum may represent BiAT. Intensive ablation targeting the central isthmus or EEB at the inferolateral RA could block the CTI bidirectionally.

Overdrive pacing mapping: An alternative approach used in scar associated localized atrial tachycardia.

BACKGROUND: Mapping and ablation of localized reentry atrial tachycardia (AT) can be challenging, especially in those with varying cycle length (CL). OBJECTIVE: We attempted to use the traditional maneuver of overdrive pacing to facilitate AT mapping. METHODS: Data were collected from 12 patients with localized ATs. All patients had prior cardiac surgery or prior atrial fibrillation ablation. Overdrive pacing mapping (ODPM) was performed to find independent local activity (ILA) and compared with conventional activation mapping (CAM) during ongoing AT to determine its accuracy and efficacy. Patients with macro-reentry AT around the tricuspid or mitral annulus were excluded. RESULTS: Twelve patients with 14 localized ATs were included. All 14 ATs including 4 (29%) with varying CL successfully completed ODPM and had the ILA, although two ATs terminated during ODP and required repeated mapping. Radiofrequency ablation focused on critical sites with ILA was successful in all 12 patients. Using CAM, however, 6 of 14 ATs (43%) mapping attempts were aborted due to AT termination (2 ATs) or varying CL (4 ATs), and only 5 of 8 (63%) located "critical sites" were ultimately confirmed by entrainment and ablation results. After 25 ± 9 months of follow-up, no patient had AT recurrence. CONCLUSION: Our preliminary results demonstrated that ODPM is superior to CAM in ATs that were poorly sustained or with varying CL and is a useful supplement to CAM.

Electrophysiological characteristics of the earliest activation site in idiopathic right ventricular outflow tract arrhythmias under mini-electrode mapping.

INTRODUCTION: Right ventricular outflow tract ventricular arrhythmias (RVOT VAs) often originate in the voltage-transitional zone. The target electrogram could be compromised by the architecture of the roving catheter. Mini-electrodes could improve the mapping resolution, especially in low-voltage areas. The aim was to assess the electrophysiological characteristics of the earliest activation site (EAS) of RVOT VAs during mapping using mini-electrodes. METHODS AND RESULTS: Twenty-seven patients with RVOT-type VAs were mapped using Orion mini-electrodes and the Rhythmia mapping system. Bipolar and unipolar electrograms were analyzed and compared with conventional ablation catheter recordings. Twenty-five patients (25 of 27) were successfully mapped and ablated at the RVOT. At the EAS, all 25 (100%) patients exhibited local sharp potentials (spiky potential) at the VAs, and 88% (22 of 25) individuals showed reverse late potentials in adjacent sinus beats on the bipolar mini-electrode recordings. Related unipolar electrograms manifested 20% "q-plateau-QS," 76% "gross QS," and 4% "late QS" patterns related to spiky potential voltages and advanced times. Compared with electrograms recorded by ablation catheter, bipolar mini-electrode recordings exhibited significantly shorter spiky potential durations (P = 0.001) and a significantly increased incidence of the reverse late potentials (P = 0.041). Unipolar mini-electrode recordings had a lower incidence ratio of "late QS" patterns (P = 0.039). CONCLUSION: Compared with ablation catheter mapping, mini-electrodes improved the mapping resolution of the EAS of RVOT VAs and exhibited shorter spiky potential durations and reduced incidence of "later QS" unipolar patterns.

AVE 0991 attenuates cardiac hypertrophy through reducing oxidative stress.

AVE 0991, the nonpeptide angiotensin-(1-7) (Ang-(1-7)) analog, is recognized as having beneficial cardiovascular effects. However, the mechanisms have not been fully elucidated. This study was designed to investigate the effects of AVE 0991 on cardiac hypertrophy and the mechanisms involved. Mice were underwent aortic banding to induce cardiac hypertrophy followed by the administration of AVE 0991 (20 mg kg·day (-1)) for 4 weeks. It was shown that AVE 0991 reduced left ventricular hypertrophy and improved heart function, characterized by decreases in left ventricular weight and left ventricular end-diastolic diameter, and increases in ejection fraction. Moreover, AVE 0991 significantly down-regulated mean myocyte diameter and attenuate the gene expression of the hypertrophic markers. Furthermore, AVE 0991 inhibited the expression of NOX 2 and NOX 4, meaning that AVE 0991 reduced oxidative stress of cardiac hypertrophy mice. Our data showed that AVE 0991 treatment could attenuate cardiac hypertrophy and improve heart function, which may be due to reduce oxidative stress.

Novel P Wave Indices to Predict Atrial Fibrillation Recurrence After Radiofrequency Ablation for Paroxysmal Atrial Fibrillation.

BACKGROUND Circumferential pulmonary vein isolation (CPVI) is a widely used treatment for paroxysmal atrial fibrillation (AF). Several P wave duration (PWD) parameters have been suggested to predict post-ablation recurrence, but their use remains controversial. This study aimed to identify novel P wave indices that predict post-ablation AF recurrence. MATERIAL AND METHODS We selected 171 consecutive patients undergoing CPVI for paroxysmal AF. Electrocardiography (ECG) recordings were obtained at the beginning and the end of ablation. PWD was measured in all 12 leads. The PWD variation was calculated by subtracting the pre-ablation PWD from the post-ablation PWD. RESULTS PWD was significantly shortened in leads II, III, aVF, and V1 after ablation. During a mean follow-up of 19.96±4.32 months, AF recurrence occurred in 32 (18.7%) patients. No significant differences in baseline characteristics or pre- or post-ablation PWD were observed between the AF recurrence and non-recurrence groups. Patients with AF recurrence exhibited a smaller PWD variation in leads II (1.21(-0.56, 2.40) vs. -5.77(-9.10, -4.06) ms, P<0.001), III (-5.92(-9.87, 3.27) vs. -9.44(-11.89, -5.57) ms, P=0.001) and V1 (-4.43(-6.64, -3.13) vs. -6.33(-8.19,-4.59) ms, P=0.003). Multivariable logistic regression analysis demonstrated that smaller PWD variations in lead II and III were independent risk factors for AF recurrence. PWD variation ≥-2.21 ms in lead II displayed the highest combined sensitivity and specificity (85.29% and 83.94%, respectively) for predicting post-ablation AF recurrence. A PWD variation ≥0 ms displayed the best practical value in predicting AF recurrence. CONCLUSIONS PWD variation in lead II is an effective predictor of post-ablation AF recurrence.

AVE 3085, a novel endothelial nitric oxide synthase enhancer, attenuates cardiac remodeling in mice through the Smad signaling pathway.

AVE 3085 is a novel endothelial nitric oxide synthase enhancer. Although AVE 3085 treatment has been shown to be effective in spontaneously restoring endothelial function in hypertensive rats, little is known about the effects and mechanisms of AVE 3085 with respect to cardiac remodeling. The present study was designed to examine the effects of AVE 3085 on cardiac remodeling and the mechanisms underlying the effects of this compound. Mice were subjected to aortic banding to induce cardiac remodeling and were then administered AVE 3085 (10 mg kg day(-1), orally) for 4 weeks. At the end of the treatment, the aortic banding-treated mice exhibited significant elevations in cardiac remodeling, characterized by an increase in left ventricular weight relative to body weight, an increase in the area of collagen deposition, an increase in the mean myocyte diameter, and increases in the gene expressions of the hypertrophic markers atrial natriuretic peptide (ANP) and ß-MHC. These indexes were significantly decreased in the AVE 3085-treated mice. Furthermore, AVE 3085 treatment reduced the expression and activation of the Smad signaling pathway in the aortic banding-treated mice. Our data showed that AVE 3085 attenuated cardiac remodeling, and this effect was possibly mediated through the inhibition of Smad signaling.

Optimization of RNA Pepper Sensors for the Detection of Arbitrary RNA Targets.

The development of fluorescent light-up RNA aptamers (FLAPs) has paved the way for the creation of sensors to track RNA in live cells. A major challenge with FLAP sensors is their brightness and limited signal-to-background ratio both in vivo and in vitro. To address this, we develop sensors using the Pepper aptamer, which exhibits superior brightness and photostability when compared to other FLAPs. The sensors are designed to fold into a low fluorescence conformation and to switch to a high fluorescence conformation through toehold or loop-mediated interactions with their RNA target. Our sensors detect RNA targets as short as 20 nucleotides in length with a wide dynamic range over 300-fold in vitro, and we describe strategies for optimizing the sensor's performance for any given RNA target. To demonstrate the versatility of our design approach, we generated Pepper sensors for a range of specific, biologically relevant RNA sequences. Our design and optimization strategies are portable to other FLAPs and offer a promising foundation for future development of RNA sensors with high specificity and sensitivity for detecting RNA biomarkers with multiple applications.

Modular RNA motifs for orthogonal phase separated compartments.

Recent discoveries in biology have highlighted the importance of protein and RNA-based condensates as an alternative to classical membrane-bound organelles. Here, we demonstrate the design of pure RNA condensates from nanostructured, star-shaped RNA motifs. We generate condensates using two different RNA nanostar architectures: multi-stranded nanostars whose binding interactions are programmed via linear overhangs, and single-stranded nanostars whose interactions are programmed via kissing loops. Through systematic sequence design, we demonstrate that both architectures can produce orthogonal (distinct and immiscible) condensates, which can be individually tracked via fluorogenic aptamers. We also show that aptamers make it possible to recruit peptides and proteins to the condensates with high specificity. Successful co-transcriptional formation of condensates from single-stranded nanostars suggests that they may be genetically encoded and produced in living cells. We provide a library of orthogonal RNA condensates that can be modularly customized and offer a route toward creating systems of functional artificial organelles for the task of compartmentalizing molecules and biochemical reactions.

Co-transcriptional production of programmable RNA condensates and synthetic organelles.

Condensation of RNA and proteins is central to cellular functions, and the ability to program it would be valuable in synthetic biology and synthetic cell science. Here we introduce a modular platform for engineering synthetic RNA condensates from tailor-made, branched RNA nanostructures that fold and assemble co-transcriptionally. Up to three orthogonal condensates can form simultaneously and selectively accumulate fluorophores through embedded fluorescent light-up aptamers. The RNA condensates can be expressed within synthetic cells to produce membrane-less organelles with a controlled number and relative size, and showing the ability to capture proteins using selective protein-binding aptamers. The affinity between otherwise orthogonal nanostructures can be modulated by introducing dedicated linker constructs, enabling the production of bi-phasic RNA condensates with a prescribed degree of interphase mixing and diverse morphologies. The in situ expression of programmable RNA condensates could underpin the spatial organization of functionalities in both biological and synthetic cells.

Rapid, Multiplexed, and Enzyme-Free Nucleic Acid Detection Using Programmable Aptamer-Based RNA Switches.

Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. We describe a class of aptamer-based RNA switches or aptaswitches that recognize target nucleic acid molecules and initiate folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide an intense fluorescent readout without intervening enzymes, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment. Aptaswitches can be used to regulate folding of seven fluorogenic aptamers, providing a general means of controlling aptamers and an array of multiplexable reporter colors. Coupling isothermal amplification reactions with aptaswitches, we reach sensitivities down to 1 RNA copy/µL in one-pot reactions. Application of multiplexed all-in-one reactions against RNA from clinical saliva samples yields an overall accuracy of 96.67% for detection of SARS-CoV-2 in 30 minutes. Aptaswitches are thus versatile tools for nucleic acid detection that are readily integrated into rapid diagnostic assays.

Rapid and Multiplexed Nucleic Acid Detection using Programmable Aptamer-Based RNA Switches.

Rapid, simple, and low-cost diagnostic technologies are crucial tools for combatting infectious disease. Here, we describe a class of aptamer-based RNA switches called aptaswitches that recognize specific target nucleic acid molecules and respond by initiating folding of a reporter aptamer. Aptaswitches can detect virtually any sequence and provide a fast and intense fluorescent readout, generating signals in as little as 5 minutes and enabling detection by eye with minimal equipment. We demonstrate that aptaswitches can be used to regulate folding of six different fluorescent aptamer/fluorogen pairs, providing a general means of controlling aptamer activity and an array of different reporter colors for multiplexing. By coupling isothermal amplification reactions with aptaswitches, we reach sensitivities down to 1 RNA copy/µL in one-pot reactions. Application of multiplexed one-pot reactions against RNA extracted from clinical saliva samples yields an overall accuracy of 96.67% for detection of SARS-CoV-2 in 30 minutes. Aptaswitches are thus versatile tools for nucleic acid detection that can be readily integrated into rapid diagnostic assays.

Characteristics of submental muscles function and hyoid bone movement in patients with dysphagia after stroke.

BACKGROUND: Dysphagia is one of the common complications after stroke. Dysphagia significantly increases the probability of serious adverse consequences. The purpose of this study was to compare the characteristics of submental muscles electromyography and hyoid motion parameters between patients with dysphagia after stroke and healthy controls, and whether there is a synergistic effect between the function of the submental muscles and the movement of the hyoid. METHODS: Fifteen patients with post-stroke dysphagia and fifteen healthy adults simultaneously underwent the videofluoroscopic and surface electromyography of the submental muscles while swallowing 5 ml of concentrated liquid barium sulphate. The electromyographic signal of the submental muscles was analysed along with parameters of hyoid movement. FINDINGS: Stage transition duration and duration of surface electromyographic activity were extended significantly in post-stroke dysphagia patients(P < 0.05). Surface electromyography amplitude and hyoid movement were significantly reduced in patients (P < 0.05). There was a significant correlation between the maximum hyoid movement distance and the peak sEMG amplitude in healthy controls (r = 0.660, P = 0.014), but not in patients with dysphagia after stroke (r = 0.425, P = 0.148). INTERPRETATION: Submental muscles electromyographic signal changes in patients may be the result of uncoordinated muscle contractions and decreased muscle strength. Furthermore, the reduced hyoid movement distance may be due to impaired function of the submental muscles. In addition, the submental muscles and hyoid movement or other swallowing structures functions were impaired to varying degrees, resulting in the disappearance of the correlation between the maximum movement distance of the hyoid and the peak amplitude.

Visually Perceived Negative Emotion Enhances Mismatch Negativity but Fails to Compensate for Age-Related Impairments.

Objective: Automatic detection of auditory stimuli, represented by the mismatch negativity (MMN), facilitates rapid processing of salient stimuli in the environment. The amplitude of MMN declines with ageing. However, whether automatic detection of auditory stimuli is affected by visually perceived negative emotions with normal ageing remains unclear. We aimed to evaluate how fearful facial expressions affect the MMN amplitude under ageing. Methods: We used a modified oddball paradigm to analyze the amplitude of N100 (N1) and MMN in 22 young adults and 21 middle-aged adults. Results: We found that the amplitude of N1 elicited by standard tones was smaller under fearful facial expressions than neutral facial expressions and was more negative for young adults than middle-aged adults. The MMN amplitude under fearful facial expressions was greater than neutral facial expressions, but the amplitude in middle-aged adults was smaller than in young adults. Conclusion: Visually perceived negative emotion promotes the extraction of auditory features. Additionally, it enhances the effect of auditory change detection in middle-aged adults but fails to compensate for this decline with normal ageing. Significance: The study may help to understand how visually perceived emotion affects the early stage of auditory information processing from an event process perspective.

Multi-arm RNA junctions encoding molecular logic unconstrained by input sequence for versatile cell-free diagnostics.

Applications of RNA-based molecular logic have been hampered by sequence constraints imposed on the input and output of the circuits. Here we show that the sequence constraints can be substantially reduced by appropriately encoded multi-arm junctions of single-stranded RNA structures. To conditionally activate RNA translation, we integrated multi-arm junctions, self-assembled upstream of a regulated gene and designed to unfold sequentially in response to different RNA inputs, with motifs of loop-initiated RNA activators that function independently of the sequence of the input RNAs and that reduce interference with the output gene. We used the integrated RNA system and sequence-independent input RNAs to execute two-input and three-input OR and AND logic in Escherichia coli, and designed paper-based cell-free colourimetric assays that accurately identified two human immunodeficiency virus (HIV) subtypes (by executing OR logic) in amplified synthetic HIV RNA as well as severe acute respiratory syndrome coronavirus-2 (via two-input AND logic) in amplified RNA from saliva samples. The sequence-independent molecular logic enabled by the integration of multi-arm junction RNAs with motifs for loop-initiated RNA activators may be broadly applicable in biotechnology.

Automatic annotation of local activation time was improved in idiopathic right ventricular outflow tract ventricular arrhythmia by novel electrogram "Lumipoint" algorithm.

PURPOSE: Precise automatic annotation of local activation time (LAT) is crucial for rapid high-density activation mapping in arrhythmia. However, it is still challenging in voltage-transitional areas where local low-amplitude near-field potentials are often obscured by large far-field potentials. The aim of this study was to explore the viability and validity of automatic identification of the earliest activation (EA) in idiopathic right ventricular outflow tract ventricular arrhythmias (RVOT VAs) using a novel Lumipoint algorithm. METHODS AND RESULTS: Twenty-seven patients with RVOT VAs were mapped with Rhythmia mapping system. Lumipoint algorithms were applied to reannotate the initial activation regions retrospectively. The results showed that LATs were reannotated in 35.0 ± 11.4% points in the initial activation area from bipolar activation breakout time (BBO) to the its 40 ms earlier timepoint. The automatically determined bipolar earliest activation time after Lumipoint reannotation (BEAT-lu: - 111.26 ± 12.13 ms) was significantly earlier than that before (BEAT: - 108.67 ± 12.25 ms, P = 0.000). Compared with manually corrected earliest activation time (EAT), the difference between EAT and BEAT-lu (DEAT-BEAT-lu: 6 (2-7) ms) was significantly smaller than that between EAT and BEAT (DEAT-BEAT/DEAT-UEA: 7 (4-11) ms, P = 0.000). The incidence of EAT and BEAT-lu being the same site was significantly higher than that between EAT and BEAT (48.15% vs 18.52%, P = 0.021). CONCLUSIONS: RVOT VAs often originate from voltage-transitional zone, and automatic annotation of LAT usually located at later high-amplitude far-field potential. Lumipoint algorithms could improve the accuracy of LAT automatic annotation, and it was plausible to ablate RVOT VAs just according to the automatically annotated BEAS-lu.

Rationale and study design for ablation of paroxysmal atrial fibrillation guided by ablation index: a multi-center, prospective randomized trial (PAF-AI trial).

BACKGROUND: Pulmonary vein isolation (PVI) has become the cornerstone of atrial fibrillation (AF) ablation, but long-term success rates remains suboptimal, due in large part to late PV reconnection and insufficient ostial substrate modification. OBJECTIVE: To evaluate whether ablation index (AI)-guided PVI with electrical isolation and quantified ostial substrate modification improves clinical outcomes when compared with contact force (CF)-guided ablation in patients with paroxysmal atrial fibrillation (PAF). METHODS: The PAF-AI trial (ChiCTR1900022041) is a prospective, multi-center, randomized controlled clinical trial enrolling patients with PAF with an indication for catheter ablation. Patients are randomized into a 2:1 fashion to two treatment arms: AI-guided PVI (n = 151) and CF-guided PVI (n = 75). In the AI-guided PVI group, real-time automated display of radiofrequency applications (Visitag™) is used with AI ≥ 500 recommended at the anterior/superior/inferior walls and 350-400 at the posterior wall. In CF-guided PVI group, the value and direction of CF are displayed, with the lesion dots manually annotated. The primary endpoint is the freedom from AF recurrence at 12 months following ablation, without antiarrhythmic drug. The primary pre-specified secondary endpoints include intraprocedural efficiency and peri-procedural complications. CONCLUSIONS: PAF-AI trial compares the effectiveness and safety of two different strategies of PVI in patients with PAF, AI-guided PVI versus more established CF-guided PVI. This prospective, multi-center, randomized controlled trial, with comparative data evaluating procedural and long-term follow-up results, aims to evaluate the impact of AI-guided strategy on AF ablation compared with the current standard of care RF ablation approach.

Thrombin and its receptor enhance ST-segment elevation in acute myocardial infarction by activating the KATP channel.

ST-segment elevation is the major clinical criterion for committing patients with chest pain to have emergent coronary revascularizations; however, the mechanism responsible for ST-segment elevation is unknown. In a guinea pig model of ST-segment elevation acute myocardial infarction (AMI), local application of hirudin, a thrombin antagonist, significantly decreased AMI-induced ST-segment elevation in a dose-dependent manner. Hirudin-induced (5 antithrombin units [ATU]) decrease in ST elevation was reversed by 250 nmol/L thrombin receptor activator peptide (TRAP). TRAP (250 nmol/L [100 microL]) significantly induced ST-segment elevation in hearts without AMI. The TRAP effect was blocked by 4 mg/kg glibenclamide and 4 mg/kg HMR1098 and partially blocked by 3 mg/kg 5HD. Pinacidil (0.45 mg/kg) simulated the effect of TRAP (250 nmol/L [100 microL]) on hearts without AMI. Moreover, single-channel recordings showed that TRAP induced ATP-sensitive K+ channel (KATP channel) activity, and this effect was blocked by HMR1098 but not 5HD. Finally, TRAP significantly shortened the monophasic action potential (MAP) at 90% repolarization (MAP90) and epicardial MAP (EpiMAP) duration. These effects of TRAP were completely reversed by HMR1098 and partially reversed by 5HD. Thrombin and its receptor activation enhanced ST-segment elevation in an AMI model by activating the sarcolemmal KATP channel.