Mitochondria-targeted sonodynamic modulation of neuroinflammation to protect against myocardial ischemia‒reperfusion injury.

Sympathetic hyperactivation and inflammatory responses are the main causes of myocardial ischemia‒reperfusion (I/R) injury and myocardial I/R-related ventricular arrhythmias (VAs). Previous studies have demonstrated that light-emitting diodes (LEDs) could modulate post-I/R neuroinflammation, thus providing protection against myocardial I/R injury. Nevertheless, further applications of LEDs are constrained due to the low penetration depth (<1 cm) and potential phototoxicity. Low-intensity focused ultrasound (LIFU), an emerging noninvasive neuromodulation strategy with deeper penetration depth (∼10 cm), has been confirmed to modulate sympathetic nerve activity and inflammatory responses. Sonodynamic therapy (SDT), which combines LIFU with sonosensitizers, confers additional advantages, including superior therapeutic efficacy, precise localization of neuronal modulation and negligible side effects. Herein, LIFU and SDT were introduced to modulate post-myocardial I/R neuroinflammation to protect against myocardial I/R injury. The results indicated that LIFU and SDT inhibited sympathetic neural activity, suppressed the activation of astrocytes and microglia, and promoted microglial polarization towards the M2 phenotype, thereby attenuating myocardial I/R injury and preventing I/R-related malignant VAs. These insights suggest that LIFU and SDT inspire a noninvasive and efficient neuroinflammatory modulation strategy with great clinical translation potential thus benefiting more patients with myocardial I/R in the future. STATEMENT OF SIGNIFICANCE: Myocardial ischemia-reperfusion (I/R) may cause I/R injury and I/R-induced ventricular arrhythmias. Sympathetic hyperactivation and inflammatory response play an adverse effect in myocardial I/R injury. Previous studies have shown that light emitting diode (LED) can regulate I/R-induced neuroinflammation, thus playing a myocardial protective role. However, due to the low penetration depth and potential phototoxicity of LED, it is difficult to achieve clinical translation. Herein, we introduced sonodynamic modulation of neuroinflammation to protect against myocardial I/R injury, based on mitochondria-targeted nanosonosensitizers (CCNU980 NPs). We demonstrated that sonodynamic modulation could promote microglial autophagy, thereby preventing myocardial I/R injury and I/R-induced ventricular arrhythmias. This is the first example of sonodynamic modulation of myocardial I/R-induced neuroinflammation, providing a novel strategy for clinical translation.

Wearable ultrasound devices: An emerging era for biomedicine and clinical translation.

In recent years, personalized diagnosis and treatment have gained significant recognition and rapid development in the biomedicine and healthcare. Due to the flexibility, portability and excellent compatibility, wearable ultrasound (WUS) devices have become emerging personalized medical devices with great potential for development. Currently, with the development of the ongoing advancements in materials and structural design of the ultrasound transducers, WUS devices have improved performance and are increasingly applied in the medical field. In this review, we provide an overview of the design and structure of WUS devices, focusing on their application for diagnosis and treatment of various diseases from a clinical application perspective, and then explore the issues that need to be addressed before clinical translation. Finally, we summarize the progress made in the development of WUS devices, and discuss the current challenges and the future direction of their development. In conclusion, WUS devices usher an emerging era for biomedicine with great clinical promise.

Potential microemboli formation risk and its management during the heated saline-enhanced radiofrequency needle-tip catheter ablation.

BACKGROUND: The potential risk of embolic events during ablation in the left ventricle (LV) with a heated saline-enhanced radiofrequency (SERF) needle-tip ablation catheter has not been characterized. OBJECTIVE: This study aimed to investigate the formation of microemboli or other untoward events during SERF ablation. METHODS: Ninety-three radiofrequency (RF) ablation procedures were performed in the LV of 14 pigs by using a SERF catheter (35 W, 70 seconds, and 60°C; normal or degassed saline [NS or DS] irrigation with a flow rate of 10 mL/min) vs a standard irrigated-tip radiofrequency (S-RF) catheter (30 or 50 W, 30 seconds, and 17 mL/min). Microbubble formation was graded on the basis of intracardiac echocardiography. Microbubbles, microembolic signals, and microparticles were monitored using our established model. RESULTS: There was no significant difference in microbubble volume among SERF-NS, SERF-DS, and S-RF 30 W with "grade 1" intracardiac echocardiography microbubbles (median and 25th-75th percentiles 0.201 [0.011-3.13], 0.455 [0.06-2.66], and 0.004 µL [0.00-0.16 µL], respectively). There was no significant difference in microembolic signals among SERF-NS, SERF-DS, and S-RF 30 W with grade 1 bubbles (n = 8.0 ± 5.8, n = 7.6 ± 4.2, and n = 6.1 ± 6.1, respectively). Both SERF-NS and SERF-DS created larger lesions than did both S-RF 30 W and S-RF 50 W deliveries (mean 1241.5 ± 658.6, 1497.7 ± 893.4, 75.0 ± 24.8, and 184.0 ± 93.8 mm3; P < .001). There was no significant difference in microparticle incidence among groups (P = .675). No evidence of embolic events was found in the brain and other organs at the histology assessment. CONCLUSION: In the setting of SERF ablation, significantly large LV lesions can be created without any increment in embolic microbubble or particle events. Grade 1 microbubble is related to the efficacy and safety.

Subarachnoid haemorrhage-induced reversible cardiac dysfunction: time course and potential mechanisms.

AIMS: Cardiac dysfunction is commonly observed in patients with subarachnoid haemorrhage (SAH). However, the specific timeline of cardiac remodelling and the underlying mechanisms responsible for this effect following SAH remain unknown. This study aims to explore the impact of SAH on cardiac dysfunction and its potential mechanisms over time. METHODS AND RESULTS: In Protocol 1, we investigated cardiac function and potential mechanisms in a Sprague-Dawley rat model of SAH at six time points (baseline and Days 1, 3, 7, 14, and 28) while exploring the underlying mechanisms. Our assessments included the haemodynamic profile, echocardiography, and the concentrations of plasma biomarkers at various time points post-SAH. We determined neuropeptide Y (NPY) 1-5 receptor protein expression levels through western blotting. In Protocol 2, we administered an NPY1 receptor antagonist to evaluate the effects of cardiac dysfunction induced by SAH on Day 3. In Protocol 1, SAH gradually provoked cardiac systolic dysfunction during the acute phase, reaching its peak on Day 3 without concurrent alterations in wall thickness. However, no significant changes were observed from Days 14 to 28 compared with Day 0. The changes in cardiac dysfunction were consistent with myocardial injury, inflammatory biomarkers, and NPY levels. SAH resulted in a heightened heart rate and systolic blood pressure, correlating with elevated epinephrine and norepinephrine levels. In Protocol 2, the administration of the NPY1 receptor antagonist effectively ameliorated cardiac dysfunction. CONCLUSIONS: SAH induces transient cardiac dysfunction in the acute phase, and the underlying mechanisms for this response involve the NPY-NPY1 receptor pathway, otherwise known as catecholamines.

The comparison between the novel technique and conventional method in the catheter ablation of premature ventricular contractions originating from the free wall of tricuspid annulus.

BACKGROUND: This study aimed to assess the safety and effectiveness of a novel technique for catheter ablation in patients with premature ventricular contraction (PVC) from the free wall of tricuspid annulus (TV). HYPOTHESIS: We hypothesized that the novel technique is more efficacious than the traditional approach. METHODS: We retrospectively investigated 59 consecutive patients with PVC originating from the free wall of TV between January 2013 and November 2021. The patients were divided into two groups: the reversed S-curve technique group (RST, n = 26) and the reversed C-curve technique group (RCT, n = 33). The RST under the support of a steerable sheath was used in RST group, while the RCT under the support of a nonsteerable sheath was used in the RCT group. Systematic mapping and radiofrequency ablation were preferentially performed under the valve in all patients. RESULTS: Compared to the RCT group, total procedural time and fluoroscopic exposure time were significantly shorter in RST group. Two patients experienced cardiac tamponade in the RCT group, while no complications were observed in RST group (p = .498). The success rate was significantly higher in RST group compared to RCT group (81.9% vs. 100%, p = .029). Three patients in RCT group failed to ablate during the operation but were successfully ablated using the novel method. During regular follow-up, no patients in the RST group had a recurrence, while three patients in the RCT group did (p = .274). CONCLUSIONS: It suggests that the reserved S-curve technique, supported by a steerable sheath, is a feasible and effective method for ablating PVC originating from the free wall of TV.

Low-intensity focused ultrasound modulation of the paraventricular nucleus to prevent myocardial infarction-induced ventricular arrhythmia.

BACKGROUND: Our previous study showed that light-emitting diode modulation of the hypothalamic paraventricular nucleus (PVN), which is the control center of the sympathetic nervous system, might attenuate neuroinflammation in the PVN and prevent ventricular arrhythmias (VAs) after myocardial infarction (MI). Low-intensity focused ultrasound (LIFU) has deeper penetration than does light-emitting diode, while its effect on the PVN has not been reported. OBJECTIVE: This study aimed to explore the effect of LIFU modulation of the PVN on the inducibility of post-MI VAs. METHODS: Fifty-four Sprague-Dawley rats were randomly divided into acute control (n = 12, 22.22%), acute MI (AMI, n = 12, 22.22%), AMI + LIFU (n = 12, 22.22%), chronic control (n = 6, 11.11%), chronic MI (CMI, n = 6, 11.11%), and CMI + LIFU (n = 6, 11.11%) groups. MI was induced by left anterior artery ligation, and electrocardiographic recording for 0.5 hours after MI and programmed electrophysiological stimulation were used to test the vulnerability of VAs. Peripheral sympathetic neural activity was assessed by measuring left stellate ganglion neural activity. Finally, hearts and brains were extracted for Western blotting and histopathological analysis, respectively. RESULTS: Compared with the AMI group, AMI-induced VAs (P < .05) and left stellate ganglion neural activity (P < .05) were significantly attenuated in the AMI + LIFU group. In addition, LIFU resulted in a significant reduction of microglial activation in the PVN and expression of inflammatory cytokines in the peri-ischemic myocardium. In the CMI + LIFU group, there was no obvious tissue damage in the brain. CONCLUSION: LIFU modulation of the PVN may prevent the incidence of post-MI VAs by attenuating MI-induced sympathetic neural activation and inflammatory response.

Transient cardiac electrophysiological changes in a rat model of subarachnoid haemorrhage: a brain-heart interaction.

AIMS: Subarachnoid haemorrhage (SAH) is one of the causes of sudden cardiac death (SCD). However, the time course of ventricular arrhythmias and potential mechanisms responsible for this effect after SAH remain unknown. OBJECTIVE: This study aims to investigate the effect of SAH on ventricular electrophysiological changes and its potential mechanisms in long-term phase. METHODS AND RESULTS: We examined the ventricular electrophysiological remodelling and potential mechanisms in a Sprague Dawley rat model of SAH at six time points (baseline, and Days 1, 3, 7, 14 and 28) and explored the potential mechanisms. We measured the ventricular effective refractory period (ERP), ventricular fibrillation threshold (VFT) and left stellate ganglion (LSG) activity at different time points before and after SAH. We also detected neuropeptide Y (NPY) levels in plasma and myocardial tissues by enzyme-linked immunosorbent assay, and quantified NPY 1 receptor (NPY1R) protein and mRNA expression levels by western blotting and quantitative real-time reverse transcription-polymerase chain reaction, respectively. Subarachnoid haemorrhage gradually prolonged QTc intervals, shortened ventricular ERP and reduced VFT during the acute phase, peaking at Day 3. However, no significant changes were observed from Days 14 to 28 compared to Day 0. Subarachnoid haemorrhage gradually increased LSG activity, increased NPY concentrations and up-regulated NPY1R expression in the acute phase of SAH, peaking at Day 3. However, no significant variations were found from Days 14 to 28 compared to Day 0. CONCLUSION: Subarachnoid haemorrhage increases the transient susceptibility of VAs in the acute phase, and the underlying mechanisms for this response included increased sympathetic activity and up-regulated NPY1R expression.

Sonodynamic therapy combined with phototherapy: Novel synergistic strategy with superior efficacy for antitumor and antiinfection therapy.

Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection therapy. Sonodynamic therapy (SDT), as a novel noninvasive therapy with a deeper penetration depth (>8 cm), fewer side effects and non-phototoxicity than PT, has drawn much attention in recent years. However, both PT and SDT have intrinsic limitations. By combining PT with SDT, the dualmodel therapy with advanced sensitizers overcome the intrinsic limitations and show higher efficacy than traditional monotherapy. Moreover, the photo-diagnosis modality could be easily integrated into synergistic therapy so that the sensitizer acts as a tracer for fluorescence/photoacoustic imaging, and the treatment process is visualized in a way that SDT combined with other therapies cannot achieve. This review summarizes the advanced sensitizers and the application of combination therapy, and explores the improvement strategies for promoting clinical transformation.

Inhibition of the NF-κB signaling pathway affects gonadal differentiation and leads to male bias in Paramisgurnus dabryanus.

In recent years, sex-controlled breeding has emerged as an effective strategy to enhance the yields of economic animals with different growth characteristics, while increasing the economic benefits of aquaculture. It is known that the NF-κB pathway participates in gonadal differentiation and reproduction. Therefore, we used the large-scale loach as a research model for the present study and selected an effective inhibitor of the NF-κB signaling pathway (QNZ). This, to investigates the impacts of the NF-κB signaling pathway on gonadal differentiation during a critical period of gonad development and after maturation. Simultaneously, the sex ratio bias and the reproductive capacities of adult fish were analyzed. Our results indicated that the inhibition of the NF-κB signaling pathway influenced the expression of genes related to gonad development, regulated the gene expression related to the brain-gonad-liver axis of juvenile loaches, and finally impacted the gonadal differentiation of the large-scale loach and promoted a male-biased sex ratio. Meanwhile, high QNZ concentrations affected the reproductive abilities of adult loaches and inhibited the growth performance of offspring. Thus, our results deepened the exploration of sex control in fish and provided a certain research basis for the sustainable development of the aquaculture industry.

Stereotactic arrhythmia radioablation: A novel therapy for cardiac arrhythmia.

Cardiac arrhythmia is a global health problem, and catheter ablation has been one of its main treatments for decades. However, catheter ablation is an invasive method that cannot reach the deep myocardium, and it carries a considerable risk of side effects and recurrence. Therefore, it is necessary to explore a novel approach. Stereotactic body radiotherapy, which has been widely used in the field of radiation oncology, has recently expanded in the treatment of cardiac arrhythmia; when used in this context, it is known as stereotactic arrhythmia radioablation (STAR). As a noninvasive, effective, and well-tolerated treatment, STAR may be a suitable alternative method for patients with cardiac arrhythmia who are resistant or intolerant to catheter ablation. The main particles used to deliver energy in STAR are photons, protons, and carbon ions. Most studies have shown the short-term effectiveness of STAR, but problems such as a high long-term recurrence rate with a cumulative ventricular tachycardia-free survival rate from the published literature of 38.6% and related complications have also emerged. Therefore, in this article, we review the application of stereotactic body radiotherapy in cardiac arrhythmia, analyze its potential problems, and explore methods for improvement.

QNZ exposure induces development toxicity and mechanisms of hatching inhibition in large-scale loach (Paramisgurnus dabryanus) embryos.

QNZ is a quinazoline-type NF-κB inhibitor and is one of the hot anti-inflammatory drug candidates in recent years. With its development and application, QNZ will inevitably enter the aquatic environment posing a threat to aquatic organisms. To investigate the potential toxicity of QNZ in the early life stages of the organism, this study exposed embryos of large-scale loach (Paramisgurnus dabryanus) to 0, 20, 40, 60, and 80 nM of QNZ. The hatching of embryos was significantly inhibited and hatching time was delayed. We explored the mechanism of hatching delay and failure. The results suggested that QNZ exposure reduced the number of hatching gland cells (HGCs) and hatching enzyme activity. Also, the frequency of spontaneous movements was inhibited by interfering with the expression of genes related to the cholinergic system and skeletal muscle development. Further, QNZ exposure induces a series of morphological changes (spine deformation, pericardial edema, tail deformation, and yolk sac edema) in embryos and newly-hatched larvae, and finally increased the deformity rate and mortality rate of newly-hatched larvae. The information presented in this study will provide a scientific basis for further studies into the potential toxicity of QNZ on aquatic organisms.

Electrophysiological characteristics of right- and left-sided Mahaim accessory pathways: A single-center experience in China.

Background: Mahaim-type accessory pathways (MAPs) are rare accessory pathways (APs) with specific properties. They are mostly located in the right side of the heart but rarely exist on the left side. Objectives: This study aims to analyze the clinical and electrophysiological (EP) characteristics of both-sided MAPs. Methods: A total of 2,249 patients with AP from our center were enrolled between 1 January 2011 and 27 March 2022. During the EP study (EPS) 17 patients were diagnosed with MAPs (right-sided: n = 13, left-sided: n = 4) according to the properties of Mahaim fibers. Results: MAPs constitute 0.75% of all APs. Out of 1,553 patients with left-sided APs, four patients (0.26%) were diagnosed with Mahaim fiber-mediated tachycardia. Out of 696 patients with right-sided APs, 13 patients (1.9%) were diagnosed with Mahaim fiber. Most Mahaim fibers were located at the free wall of the tricuspid and mitral annuli. Seven patients of right-sided MAPs were of atriofasicular type, six patients had right-sided MAPs, and all of the patients with left-sided MAPs were of atrioventricular (AV) type. The M potential only was detected in long-length MAPs. Coexistence with other supraventricular tachycardias (SVTs) was also observed both in patients with right-sided and left-sided MAPs. All the patients underwent radiofrequency ablation successfully. Only one patient had tachycardia recurrence during a follow-up. Conclusion: Although MAPs are commonly located at right sides, left sites are not impossible. The M potential contributes to the improvement of the successful ablation.

Bedside temporary transvenous cardiac pacing lead placement in patients with tricuspid valve surgery without guidance of X-ray: A single-center experience.

BACKGROUND: It is difficult to insert cardiac pacing leads in patient with tricuspid valve surgery (TVS). The aim of this study was to evaluate safety and effectiveness of a novel technique applied for bedside temporary pacemaker placement (TPP) in patients with TVS. METHODS: We investigated patients with TVS who required bedside TPP without X-ray guidance in cardiac intensive care unit between January 2019 and March 2022. They were divided into Novel pre-shaped group (N = 21) and Control group (routine pre-shaped group, N = 26). The ordinary bipolar electrodes were applied in both groups. In Novel pre-shaped group, electrodes were reshaped by a novel technique with three-curve with anterior tip method, while electrodes were shaped by traditional strategy in Control group. We evaluated the operation duration, first-attempt success rate of the lead placement, pacing threshold, success rate of lead placement, the rate of leads displacement, and complications. RESULTS: Compared with that in Control group, the procedure time was significantly shortened and the first-attempt success rate of lead placement was obviously increased in Novel pre-shaped group (both p < 0.05). Although there was a slight reduction in complications in Novel pre-shaped group when compared with that in Control group. However, there were no statistical significance in pacing threshold, the success rate of lead placement, the rate of leads displacement, and complications when compared between two groups. CONCLUSIONS: We propose a novel technique, three-curve with anterior tip method, is a feasible and effective bedside method to insert emergency temporary pacing leads in patients with TVS.

Non-invasive tragus stimulation improves cardiac post-ischemic remodeling by regulating cardiac parasympathetic activity.

AIMS: Our previous study proved that low-level tragus nerve stimulation (LL-TS) could improve left ventricular remodelling by cardiac down-stream mechanisms. However, the cardiac up-stream mechanisms remain unknown. METHODS AND RESULTS: Twenty-eight adult beagle dogs were randomly divided into an MI group (myocardial infarction was induced by permanent ligation of the left coronary artery, n = 10), an LL-TS group (MI plus intermittent LL-TS treatment, n = 10), and a control group (sham ligation with the same stimulation as the LL-TS group, n = 8). Auricular tragus nerve was bilaterally delivered to the tragus via ear-clips connected to a custom-made stimulator. The voltage slowing sinus rate was used as the threshold to set the LL-TS 80% below this level. At the end of 4 weeks post-MI, LL-TS could significantly increase atrial ganglion plex (GP) activity, decreased left stellate ganglion (LSG) activity, reduced LV dilation, and improved ventricular functions. Chronic intermittent LL-TS treatment significantly attenuated left ventricular remodelling via the up-regulation of α7nAChR expression and the down-regulation of MMP-9 level in post-MI LV tissue. The elevated protein and mRNA of MMP-9 levels in remote areas were significantly ameliorated by LL-TS treatment. CONCLUSIONS: Chronic LL-TS increased GP neural activity and improved ventricular remodelling possibly via α7nAChR/MMP-9 axis.

Association between adiponectin-to-leptin ratio and heart rate variability in new-onset paroxysmal atrial fibrillation: A retrospective cohort study.

BACKGROUND: The adiponectin-to-leptin (A/L) ratio has been identified as a potential surrogate biomarker for metabolic disorders. However, it remains unknown whether the serum A/L ratio is associated with heart rate variability in paroxysmal atrial fibrillation (AF). METHODS: For this retrospective study, we included consecutive patients who underwent 24-h long-range electrocardiogram examination in our center for paroxysmal AF. The results of echocardiography, heart rate variability tests, and blood tests were also retrieved. Multivariate line regression analysis was performed to evaluate identify factors independently associated with heart rate variability. RESULTS: Among the 85 included patients with paroxysmal AF, the median A/L ratio was 1.71. Univariate analysis indicated that patients with a low A/L ratio (<1.71, n = 42) had a lower high-frequency (HF) power and a higher hs-CRP level, low-frequency (LF) power, and LF/HF ratio than those with a high A/L ratio (≥1.71, n = 43). Multivariate linear regression analysis showed that the serum leptin concentration was independently and positively associated with LF (ß = 0.175, p = .028), while the serum adiponectin concentration was independently and positively associated with HF (ß = 0.321, p = .001). Moreover, the A/L ratio was independently and negatively associated with the LF/HF ratio (ß = -0.276, p = .007). CONCLUSIONS: The A/L ratio was independently and negatively associated with the LF/HF ratio in patients with new-onset paroxysmal AF.

Feasibility and Safety of Left Bundle Branch Pacing for Advance Aged Patients: A Multicenter Comparative Study.

Background: Left bundle branch pacing (LBBP) has been shown to be a safe and effective means to achieve physiological pacing. However, elderly patients have increased risks from invasive procedures and the risk of LBBP in elderly patients is not known. We aimed to investigate the safety and efficacy of LBBP in elderly patients >80 years of age. Methods: From December 2017 to June 2019, 346 consecutive patients with symptomatic bradycardia, 184 patients under 80 years of age and 162 over 80 years, were included and underwent LBBP. The safety and prognosis of LBBP were comparatively evaluated by measured pacing parameters, periprocedural complications, and follow-up clinical events. Results: Compared with the younger, the elderly group had worse baseline cardiac and renal function. LBBP was achieved successfully in both groups with comparable fluoroscopic time and paced QRS duration (110.0 [102.0, 118.0] ms for the young vs. 110.0 [100.0, 120.0] ms for the elderly, P = 0.874). Through a follow-up of 20.0 ± 6.1 months, pacing parameters were stable while higher threshold and impedance were observed in the elderly group. In the evaluation of safety, overall procedure-related complication rates were comparable (4.4 vs. 3.8%, young vs. elderly). For prognosis, similar rates of major adverse cardiocerebrovascular events (7.1 vs. 11.9%, young vs. elderly) were observed. Conclusions: Compared to younger patients, LBBP could achieve physiological pacing in patients over 80 with comparable midterm safety and prognosis. Long-term safety and benefits of LBBP, however, necessitate further evaluation.

Pulsed Field Ablation of Superior Vena Cava: Feasibility and Safety of Pulsed Field Ablation.

Background: Studies have shown that pulsed field ablation (PFA) has excellent effectiveness and safety in pulmonary vein isolation (PVI). However, there are few reports about the application of PFA, especially the alternating current (AC) biphase PFA, in superior vena cava (SVC) isolation, and its effectiveness and safety are still unclear. Objective: To investigate the efficacy and safety of the AC biphase PFA for SVC isolation, and to provide evidence for the clinical use of PFA for SVC. Methods: Eight pigs and two dogs were included in the study. PFA was delivered to these pigs and dogs. Pacing threshold and electrogram data were recorded before and after PFA. Voltage mapping of SCV was obtained before, after, and 3 weeks after PFA. At the end, all animals were euthanatized for gross pathology analysis. Results: For eight pigs, the median pacing threshold was 1.5 (1.4, 2.75) mA before PFA, while > 6.0 mA after PFA for all animals. The average electrogram amplitude reduction was 61.33 ± 24.90% for ablations with the initial amplitude≥0.5 mv. For two dogs, pacing threshold change and electrogram amplitude reduction were also observed. No phrenic palsy or sinus node injury was observed during PFA in any animal. Furthermore, voltage mapping showed that the voltage amplitude was significantly decreased in all animals and this could be kept for more than 3 weeks. Moreover, transmural tissue damage with reserved vessel and nerve were shown, no SVC stenosis was found at 3 weeks after PFA. Conclusion: PFA can effectively isolate SVC. Transmural tissue damage of SVC can be achieved without phrenic palsy, sinus node injury nor SVC stenosis.

Alteration of Autonomic Nervous System Is Associated With Severity and Outcomes in Patients With COVID-19.

BACKGROUND: Previous studies suggest that coronavirus disease 2019 (COVID-19) is a systemic infection involving multiple systems, and may cause autonomic dysfunction. OBJECTIVE: To assess autonomic function and relate the findings to the severity and outcomes in COVID-19 patients. METHODS: We included consecutive patients with COVID-19 admitted to the 21st COVID-19 Department of the east campus of Renmin Hospital of Wuhan University from February 6 to March 7, 2020. Clinical data were collected. Heart rate variability (HRV), N-terminal pro-B-type natriuretic peptide (NT-proBNP), D-dimer, and lymphocytes and subsets counts were analysed at two time points: nucleic-acid test positive and negative. Psychological symptoms were assessed after discharge. RESULTS: All patients were divided into a mild group (13) and a severe group (21). The latter was further divided into two categories according to the trend of HRV. Severe patients had a significantly lower standard deviation of the RR intervals (SDNN) (P < 0.001), standard deviation of the averages of NN intervals (SDANN) (P < 0.001), and a higher ratio of low- to high-frequency power (LF/HF) (P = 0.016). Linear correlations were shown among SDNN, SDANN, LF/HF, and laboratory indices (P < 0.05). Immune function, D-dimer, and NT-proBNP showed a consistent trend with HRV in severe patients (P < 0.05), and severe patients without improved HRV parameters needed a longer time to clear the virus and recover (P < 0.05). CONCLUSION: HRV was associated with the severity of COVID-19. The changing trend of HRV was related to the prognosis, indicating that HRV measurements can be used as a non-invasive predictor for clinical outcome.

Real-time intracardiac echocardiography validation of saline-enhanced radiofrequency needle-tip ablation: lesion characteristics and gross pathology correlation.

AIMS: With the implementation of saline-enhanced radiofrequency (SERF) needle-tip ablation, real-time validation of lesion formation is needed for the controllable creation of transmural lesions. The aim of the study was to analyse the ability of two-dimensional intracardiac echocardiography (2D-ICE) to guide and validate SERF ablation in real-time. METHODS AND RESULTS: Fifty-six SERF energy deliveries at left ventricular sites of 11 dogs guided by 2D-ICE were analysed (power: 15-50 W; time: 25-120 s; irrigation saline: 60°C with 10 mL/min flow rate). Catheter tip/tissue orientation and lesion formation could be well detected by 2D-ICE in 49 (87.5%) energy deliveries. Gross pathology analysis confirmed excellent 2D-ICE lesion localization, the ability to detect transmural lesions (70% sensitivity, 47% specificity) and positive correlation between 2D-ICE and the corresponding gross pathology measurements of 'maximal lesion depth'; (repeated measures correlation: rrm = 0.43, P = 0.012) and 'depth at maximal lesion width' (D@MW; rrm = 0.51, P = 0.003). The median angle between SERF catheter tip and endocardium was 76° [interquartile range (IQR) 58-83°]. The more perpendicular the catheter tip/tissue orientation was the deeper D@MW (rrm = 0.32, P = 0.045). Grade 3 microbubbles on 2D-ICE during ablation, indicating inadequate catheter tip/tissue contact, was associated with smaller lesion volumes than with Grade 1 microbubbles (284.8 mm3 [IQR 151.3-343.1] vs. 2114.1 mm3 [IQR 1437.0-3026.3], P < 0.001). CONCLUSION: With excellent lesion localization and a 70% detection rate of transmural lesions, 2D-ICE is well suited to validate SERF ablation lesion formation in real-time. The catheter tip/tissue angle impacts the lesion formation and through perpendicular catheter positioning, deeper intramural areas of the myocardium can be reached.

Association between Serum Adiponectin and Atrial Fibrillation: A Case-Control Study Stratified by Age and Gender.

BACKGROUND: Circulating adiponectin has been suggested to be associated with atrial fibrillation (AF). However, whether the association differs by age and gender remains unknown. We performed a case-control study to evaluate the above association. METHODS: AF patients who underwent 24-hour long-range 12-channel electrocardiogram examination at our center were included in this study, and people with normal sinus rhythm (NSR) were included as controls. All participants underwent echocardiography and heart rate variability tests. Biochemical parameters and adiponectin levels were also evaluated. Receiver operating characteristic (ROC) analyses were used to determine the predictive efficacy of adiponectin for AF, and multivariate logistic regression analysis was performed to evaluate the potential independent predictors of AF. RESULTS: Overall, 84 patients with AF and 84 people with NSR were included. Serum adiponectin was significantly higher in AF patients compared to that in controls (P < 0.001). ROC analysis showed that higher serum adiponectin (>6.098 µg/mL) had predictive efficacy for AF, with an area under the curve of 0.660 (95% confidence interval [CI]: 577-0.742). The results of multivariate logistic regression analysis showed that higher adiponectin was an independent predictor of AF in the overall participants (odds ratio [OR] 1.224, 95% CI 1.018-1.471, P=0.032). Subgroup analysis showed that higher adiponectin was independently associated with AF in women (OR 1.893, 95% CI 1.160-3.089, P=0.011) and in patients aged < 65 years (OR 1.453, 95% CI 1.023-2.064, P=0.037), but not in men or those aged ≥ 65 years. CONCLUSIONS: Higher serum adiponectin level was independently associated with higher odds for AF in women and in participants <65 years old, but not in men or those aged ≥65 years.