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1.
APL Bioeng ; 8(2): 026107, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38694891

ABSTRACT

Establishing quantitative parameters for differentiating between healthy and diseased cartilage tissues by examining collagen fibril degradation patterns facilitates the understanding of tissue characteristics during disease progression. These findings could also complement existing clinical methods used to diagnose cartilage-related diseases. In this study, cartilage samples from normal, osteoarthritis (OA), and rheumatoid arthritis (RA) tissues were prepared and analyzed using polarization-resolved second harmonic generation (P-SHG) imaging and quantitative image texture analysis. The enhanced molecular contrast obtained from this approach is expected to aid in distinguishing between healthy and diseased cartilage tissues. P-SHG image analysis revealed distinct parameters in the cartilage samples, reflecting variations in collagen fibril arrangement and organization across different pathological states. Normal tissues exhibited distinct χ33/χ31 values compared with those of OA and RA, indicating collagen type transition and cartilage erosion with chondrocyte swelling, respectively. Compared with those of normal tissues, OA samples demonstrated a higher degree of linear polarization, suggesting increased tissue birefringence due to the deposition of type-I collagen in the extracellular matrix. The distribution of the planar orientation of collagen fibrils revealed a more directional orientation in the OA samples, associated with increased type-I collagen, while the RA samples exhibited a heterogeneous molecular orientation. This study revealed that the imaging technique, the quantitative analysis of the images, and the derived parameters presented in this study could be used as a reference for disease diagnostics, providing a clear understanding of collagen fibril degradation in cartilage.

2.
Front Cardiovasc Med ; 11: 1306055, 2024.
Article in English | MEDLINE | ID: mdl-38689859

ABSTRACT

Introduction: Signal-averaged electrocardiography (SAECG) provides diagnostic and prognostic information regarding cardiac diseases. However, its value in other nonischemic cardiomyopathies (NICMs) remains unclear. This study aimed to investigate the role of SAECG in patients with NICM. Methods and results: This retrospective study included consecutive patients with NICM who underwent SAECG, biventricular substrate mapping, and ablation for ventricular arrhythmia (VA). Patients with baseline ventricular conduction disturbances were excluded. Patients who fulfilled at least one SAECG criterion were categorized into Group 1, and the other patients were categorized into Group 2. Baseline and ventricular substrate characteristics were compared between the two groups. The study included 58 patients (39 men, mean age 50.4 ± 15.5 years), with 34 and 24 patients in Groups 1 and 2, respectively. Epicardial mapping was performed in eight (23.5%) and six patients (25.0%) in Groups 1 and 2 (p = 0.897), respectively. Patients in Group 1 had a more extensive right ventricular (RV) low-voltage zone (LVZ) and scar area than those in Group 2. Group 1 had a larger epicardial LVZ than Group 2. Epicardial late potentials were more frequent in Group 1 than in Group 2. There were more arrhythmogenic foci within the RV outflow tract in Group 1 than in Group 2. There was no significant difference in long-term VA recurrence. Conclusion: In our NICM population, a positive SAECG was associated with a larger RV endocardial scar, epicardial scar/late potentials, and a higher incidence of arrhythmogenic foci in the RV outflow tract.

3.
J Chin Med Assoc ; 87(5): 471-479, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38380919

ABSTRACT

BACKGROUND: Preoperative estimation of the volume of the left atrium (LA) and epicardial adipose tissue (EAT) on computed tomography (CT) images is associated with an increased risk of atrial fibrillation (AF) recurrence. We aimed to design a deep learning-based workflow to provide reliable automatic segmentation of the atria, pericardium, and EAT for future applications in the management of AF. METHODS: This study enrolled 157 patients with AF who underwent first-time catheter ablation between January 2015 and December 2017 at Taipei Veterans General Hospital. Three-dimensional (3D) U-Net models of the LA, right atrium (RA), and pericardium were used to develop a pipeline for total, LA-EAT, and RA-EAT automatic segmentation. We defined fat within the pericardium as tissue with attenuation between -190 and -30 HU and quantified the total EAT. Regions between the dilated endocardial boundaries and endocardial walls of the LA or RA within the pericardium were used to detect voxels attributed to fat, thus estimating LA-EAT and RA-EAT. RESULTS: The LA, RA, and pericardium segmentation models achieved Dice coefficients of 0.960 ± 0.010, 0.945 ± 0.013, and 0.967 ± 0.006, respectively. The 3D segmentation models correlated well with the ground truth for the LA, RA, and pericardium ( r = 0.99 and p < 0.001 for all). The Dice coefficients of our proposed method for EAT, LA-EAT, and RA-EAT were 0.870 ± 0.027, 0.846 ± 0.057, and 0.841 ± 0.071, respectively. CONCLUSION: Our proposed workflow for automatic LA, RA, and EAT segmentation using 3D U-Nets on CT images is reliable in patients with AF.


Subject(s)
Adipose Tissue , Atrial Fibrillation , Deep Learning , Heart Atria , Pericardium , Tomography, X-Ray Computed , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Adipose Tissue/diagnostic imaging , Pericardium/diagnostic imaging , Heart Atria/diagnostic imaging , Male , Female , Middle Aged , Aged , Workflow , Epicardial Adipose Tissue
4.
Circ J ; 2024 Feb 14.
Article in English | MEDLINE | ID: mdl-38355108

ABSTRACT

BACKGROUND: The aim of this study was to build an auto-segmented artificial intelligence model of the atria and epicardial adipose tissue (EAT) on computed tomography (CT) images, and examine the prognostic significance of auto-quantified left atrium (LA) and EAT volumes for AF.Methods and Results: This retrospective study included 334 patients with AF who were referred for catheter ablation (CA) between 2015 and 2017. Atria and EAT volumes were auto-quantified using a pre-trained 3-dimensional (3D) U-Net model from pre-ablation CT images. After adjusting for factors associated with AF, Cox regression analysis was used to examine predictors of AF recurrence. The mean (±SD) age of patients was 56±11 years; 251 (75%) were men, and 79 (24%) had non-paroxysmal AF. Over 2 years of follow-up, 139 (42%) patients experienced recurrence. Diabetes, non-paroxysmal AF, non-pulmonary vein triggers, mitral line ablation, and larger LA, right atrium, and EAT volume indices were linked to increased hazards of AF recurrence. After multivariate adjustment, non-paroxysmal AF (hazard ratio [HR] 0.6; 95% confidence interval [CI] 0.4-0.8; P=0.003) and larger LA-EAT volume index (HR 1.1; 95% CI 1.0-1.2; P=0.009) remained independent predictors of AF recurrence. CONCLUSIONS: LA-EAT volume measured using the auto-quantified 3D U-Net model is feasible for predicting AF recurrence after CA, regardless of AF type.

5.
Int J Cardiol ; 402: 131851, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38360099

ABSTRACT

BACKGROUND: Based solely on pre-ablation characteristics, previous risk scores have demonstrated variable predictive performance. This study aimed to predict the recurrence of AF after catheter ablation by using artificial intelligence (AI)-enabled pre-ablation computed tomography (PVCT) images and pre-ablation clinical data. METHODS: A total of 638 drug-refractory paroxysmal atrial fibrillation (AF) patients undergone ablation were recruited. For model training, we used left atria (LA) acquired from pre-ablation PVCT slices (126,288 images). A total of 29 clinical variables were collected before ablation, including baseline characteristics, medical histories, laboratory results, transthoracic echocardiographic parameters, and 3D reconstructed LA volumes. The I-Score was applied to select variables for model training. For the prediction of one-year AF recurrence, PVCT deep-learning and clinical variable machine-learning models were developed. We then applied machine learning to ensemble the PVCT and clinical variable models. RESULTS: The PVCT model achieved an AUC of 0.63 in the test set. Various combinations of clinical variables selected by I-Score can yield an AUC of 0.72, which is significantly better than all variables or features selected by nonparametric statistics (AUCs of 0.66 to 0.69). The ensemble model (PVCT images and clinical variables) significantly improved predictive performance up to an AUC of 0.76 (sensitivity of 86.7% and specificity of 51.0%). CONCLUSIONS: Before ablation, AI-enabled PVCT combined with I-Score features was applicable in predicting recurrence in paroxysmal AF patients. Based on all possible predictors, the I-Score is capable of identifying the most influential combination.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Humans , Atrial Fibrillation/diagnostic imaging , Atrial Fibrillation/surgery , Artificial Intelligence , Treatment Outcome , Heart Atria/diagnostic imaging , Heart Atria/surgery , Catheter Ablation/methods , Recurrence , Predictive Value of Tests
6.
Front Cardiovasc Med ; 11: 1305485, 2024.
Article in English | MEDLINE | ID: mdl-38292242

ABSTRACT

Introduction: Catheter ablation is an effective and safe strategy for treating atrial fibrillation patients. Nevertheless, studies on the long-term outcomes of catheter ablation in patients with dilated cardiomyopathy are limited. This study aimed to assess the electrophysiological characteristics of atrial fibrillation patients with dilated cardiomyopathy and compare the long-term clinical outcomes between patients undergoing catheter ablation and medical therapy. Method: Patient baseline characteristics and electrophysiological parameters were examined to identify the predictors of atrial fibrillation recurrence following catheter ablation. The clinical outcomes of catheter ablation and medical therapy were compared using the propensity score matched method. Results: A total of 343 patients were enrolled, with 46 in the catheter ablation group and 297 in the medical therapy group. Among the catheter ablation group, 58.7% (n = 27) had persistent atrial fibrillation. The recurrence rate of atrial arrhythmia was 30.4% (n = 14) after an average follow-up duration of 7.7 years following catheter ablation. The only predictive factor for atrial fibrillation recurrence after catheter ablation was the left atrial diameter. When compared to medical therapy, catheter ablation demonstrated significantly better outcomes in terms of overall survival, freedom from heart failure hospitalization, improvement in left ventricular ejection fraction, and a greater reduction in left ventricular diameter and left atrial diameter after propensity score matching. Conclusions: Therefore, catheter ablation proves to be effective in providing long-term control of atrial fibrillation in patients with dilated cardiomyopathy. In addition to standard heart failure care, catheter ablation significantly enhanced both morbidity and mortality outcomes and reversed structural remodeling when compared to heart failure medication alone.

7.
J Cardiol ; 83(5): 306-312, 2024 May.
Article in English | MEDLINE | ID: mdl-37838339

ABSTRACT

BACKGROUND: Modifying the autonomic system after catheter ablation may prevent the recurrence of atrial fibrillation (AF). Evaluation of skin sympathetic nerve activity (SKNA) is a noninvasive method for the assessment of sympathetic activity. However, there are few studies on the effects of different energy settings on SKNA. OBJECTIVE: To investigate the changes in SKNA in different energy settings and their relationship to AF ablation outcomes. METHODS: Seventy-two patients with paroxysmal and persistent AF were enrolled. Forty-three patients received AF ablation with the conventional (ConV) energy setting (low power for long duration), and 29 patients using a high-power, short-duration (HPSD) strategy. The SKNA was acquired from the right arm 1 day before and after the radiofrequency ablation. We analyzed the SKNA and ablation outcomes in the different energy settings. RESULTS: Both groups had a similar baseline average SKNA (aSKNA). We found that the median aSKNA increased significantly from 446.82 µV to 805.93 µV (p = 0.003) in the ConV group but not in the HPSD group. In the ConV group, patients without AF recurrence had higher aSKNA values. However, the 1-year AF recurrence rate remained similar between both groups (35 % vs. 28 %, p = 0.52). CONCLUSION: The post-ablation aSKNA levels increased significantly in the ConV group but did not change significantly in the HPSD group, which may reflect different neuromodulatory effects. However, the one-year AF recurrence rates were similar for both groups. These results demonstrate that the HPSD strategy has durable lesion creation but less lesion depth, which may reduce collateral damage.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Sympathetic Nervous System , Catheter Ablation/methods , Treatment Outcome , Pulmonary Veins/surgery , Recurrence
8.
J Cardiovasc Electrophysiol ; 35(1): 60-68, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37888200

ABSTRACT

INTRODUCTION: Carina breakthrough (CB) at the right pulmonary vein (RPV) can occur after circumferential pulmonary vein isolation (PVI) due to epicardial bridging or transient tissue edema. High-power short-duration (HPSD) ablation may increase the incidence of RPV CB. Currently, the surrogate of ablation parameters to predict RPV CB is not well established. This study investigated predictors of RPV CB in patients undergoing ablation index (AI)-guided PVI with HPSD. METHODS: The study included 62 patients with symptomatic atrial fibrillation (AF) who underwent AI-guided PVI using HPSD. Patients were categorized into two groups based on the presence or absence of RPV CB. Lesions adjacent to the RPV carina were assessed, and CB was confirmed through residual voltage, low voltage along the ablation lesions, and activation wavefront propagation. RESULTS: Out of the 62 patients, 21 (33.87%) experienced RPV CB (Group 1), while 41 (66.13%) achieved first-pass RPV isolation (Group 2). Despite similar AI and HPSD, patients with RPV CB had lower contact force (CF) at lesions adjacent to the RPV carina. Receiver operating characteristic (ROC) curve analysis identified CF < 10.5 g as a predictor of RPV CB, with 75.7% sensitivity and 56.2% specificity (area under the curve: 0.714). CONCLUSION: In patients undergoing AI-guided PVI with HPSD, lower CF adjacent to the carina was associated with a higher risk of RPV CB. These findings suggest that maintaining higher CF during ablation in this region may reduce the occurrence of RPV CB.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Pulmonary Veins/surgery , Catheter Ablation/adverse effects , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Treatment Outcome , Recurrence
9.
JAMA Netw Open ; 6(11): e2344535, 2023 Nov 01.
Article in English | MEDLINE | ID: mdl-37991761

ABSTRACT

Importance: Catheter ablation for persistent atrial fibrillation (AF) has shown limited success. Objective: To determine whether AF drivers could be accurately identified by periodicity and similarity (PRISM) mapping ablation results for persistent AF when added to pulmonary vein isolation (PVI). Design, Setting, and Participants: This prospective randomized clinical trial was performed between June 1, 2019, and December 31, 2020, and included patients with persistent AF enrolled in 3 centers across Asia. Data were analyzed on October 1, 2022. Intervention: Patients were assigned to the PRISM-guided approach (group 1) or the conventional approach (group 2) at a 1:1 ratio. Main Outcomes and Measures: The primary outcome was freedom from AF or other atrial arrhythmia for longer than 30 seconds at 6 and 12 months. Results: A total of 170 patients (mean [SD] age, 62.0 [12.3] years; 136 men [80.0%]) were enrolled (85 patients in group 1 and 85 patients in group 2). More group 1 patients achieved freedom from AF at 12 months compared with group 2 patients (60 [70.6%] vs 40 [47.1%]). Multivariate analysis indicated that the PRISM-guided approach was associated with freedom from the recurrence of atrial arrhythmia (hazard ratio, 0.53 [95% CI, 0.33-0.85]). Conclusions and Relevance: The waveform similarity and recurrence pattern derived from high-density mapping might provide an improved guiding approach for ablation of persistent AF. Compared with the conventional procedure, this novel specific substrate ablation strategy reduced the frequency of recurrent AF and increased the likelihood of maintenance of sinus rhythm. Trial Registration: ClinicalTrials.gov Identifier: NCT05333952.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Male , Humans , Middle Aged , Atrial Fibrillation/surgery , Prospective Studies , Asia , Multivariate Analysis
10.
Front Cardiovasc Med ; 10: 1265890, 2023.
Article in English | MEDLINE | ID: mdl-37953760

ABSTRACT

Background: Atrial fibrillation (AF) and mitral regurgitation (MR) have a complex interplay. Catheter ablation (CA) of AF may be a potential method to improve the severity of MR in AF patients. Methods: Patients with symptomatic AF and moderate to severe MR who underwent catheter ablation from 2011 to 2021 were retrospectively included in the study. Patients' baseline characteristics and electrophysiological features were examined. These patients were classified as group 1 with improved MR and group 2 with refractory MR after CA. Results: Fifty patients (age 60.2 ± 11.6 years, 29 males) were included in the study (32 in group 1 and 18 in group 2). Group 1 patients had a lower CHA2DS2-VASc score (1.7 ± 1.5 vs. 2.7 ± 1.5, P = 0.005) and had a lower incidence of hypertension (28.1% vs. 66.7%, P = 0.007) and diabetes mellitus (3.1% vs. 22.2%, P = 0.031) as compared to group 2 patients. Electroanatomic three-dimensional (3D) mapping showed that group 1 patients demonstrated less scars on the posterior bottom of the left atrium compared to group 2 patients (12.5% vs. 66.7%, P < 0.001). AF recurrence was not different between the two groups. After multivariate logistic regression analysis, a posterior bottom scar in the left atrium independently predicted refractory MR despite successful AF ablation. Conclusion: Most patients with AF and MR showed improvement of MR after AF ablation. A scar involving the posterior bottom of the left atrium is associated with poor recovery of MR.

11.
J Cardiovasc Electrophysiol ; 34(12): 2504-2513, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37822117

ABSTRACT

INTRODUCTION: Despite undergoing an index ablation, some patients progress from paroxysmal atrial fibrillation (PAF) to persistent AF (PersAF), and the mechanism behind this is unclear. The aim of this study was to investigate the predictors of progression to PersAF after catheter ablation in patients with PAF. METHODS: This study included 400 PAF patients who underwent an index ablation between 2015 and 2019. The patients were classified into three groups based on their outcomes: Group 1 (PAF to sinus rhythm, n = 226), Group 2 (PAF to PAF, n = 146), and Group 3 (PAF to PersAF, n = 28). Baseline and procedural characteristics were collected, and predictors for AF recurrence and progression were evaluated. RESULTS: The mean age of the patients was 58.4 ± 11.1 years, with 272 males. After 3 years of follow-up, 7% of the PAF cases recurred and progressed to PersAF despite undergoing an index catheter ablation. In the multivariable analysis, a larger left atrial (LA) diameter and the presence of non-pulmonary vein (PV) triggers during the index procedure independently predicted recurrence. Moreover, a larger LA diameter, the presence of non-PV triggers, and a history of thyroid disease independently predicted AF progression. CONCLUSION: The progression from PAF to PersAF after catheter ablation is associated with a larger LA diameter, history of thyroid disease, and the presence of non-PV triggers. Meticulous preprocedural evaluation, patient selection, and comprehensive provocation tests during catheter ablation are recommended.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Thyroid Diseases , Male , Humans , Middle Aged , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/surgery , Treatment Outcome , Pulmonary Veins/surgery , Catheter Ablation/adverse effects , Catheter Ablation/methods , Recurrence
12.
Circ J ; 87(12): 1750-1756, 2023 11 24.
Article in English | MEDLINE | ID: mdl-37866912

ABSTRACT

BACKGROUND: Circumferential pulmonary vein isolation (CPVI) has supplanted segmental PVI (SPVI) as standard procedure for atrial fibrillation (AF). However, there is limited evidence examining the efficacy of these strategies in redo ablations. In this study, we investigated the difference in recurrence rates between SPVI and CPVI in redo ablations for PV reconnection.Methods and Results: This study retrospectively enrolled 543 patients who had undergone AF ablation between 2015 and 2017. Among them, 167 patients (30.8%, including 128 male patients and 100 patients with paroxysmal AF) underwent redo ablation for recurrent AF. Excluding 26 patients without PV reconnection, 141 patients [90 patients of SPVI (Group 1) and 51 patients of CPVI (Group 2)] were included. The AF-free survival rates were 53.3% and 56.9% in Group 1 and Group 2, respectively (P=0.700). The atrial flutter (AFL)-free survival rates were 90% and 100% in Group 1 and Group 2, respectively (P=0.036). The ablation time was similar between groups, and there no major complications were observed. CONCLUSIONS: For redo AF ablation procedures, SPVI and CPVI showed similar outcomes, except for a higher AFL recurrence rate for SPVI after long-term follow-up (>2 years). This may be due to a higher probability of residual PV gaps causing reentrant AFL.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Male , Atrial Fibrillation/surgery , Pulmonary Veins/surgery , Retrospective Studies , Treatment Outcome , Recurrence , Catheter Ablation/adverse effects , Catheter Ablation/methods
13.
J Arrhythm ; 39(5): 801-802, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37799788
14.
BMC Med Inform Decis Mak ; 23(1): 163, 2023 08 22.
Article in English | MEDLINE | ID: mdl-37608374

ABSTRACT

BACKGROUND: Treatment with oral anticoagulants (OACs) could prevent stroke in atrial fibrillation (AF), but side effects developed due to OACs may cause patients anxiety during decision making. This study aimed to investigate whether shared decision making (SDM) reduces anxiety and improves adherence to stroke prevention measures in patients with AF. METHODS: A one-group pretest-posttest design using a questionnaire survey was applied at the outpatient cardiology clinic between July 2019 until September 2020. A Patient Decision Aid (PDA) tool was used for the completion of the questionnaire survey after health education and counseling. Ten questions were included for patients' recognition of SDM, and a 5-point scoring method was used, where "very much" was scored as 5 points, and "totally not" was scored as 1 point. RESULTS: Fifty-two patients with AF were enrolled. In terms of patients' recognition of SDM, points of more than 4.17 out of 5 were noted, indicating recognition above the level of "very much." The patients' anxiety scores before SDM were 3.56 (1.2), with a decrease of 0.64 points (p < 0.001) to 2.92 (1.3) after SDM. After SDM, the number of patients who decided to take OAC increased from 76.9% to 88.5%, and the 15.4% answering "unclear" decreased to 1.9% (p = 0.006). The patients' anxiety levels after SDM were associated with gender (p = 0.025). CONCLUSIONS: The approach using SDM enhanced our understanding of the pros and cons of OAC treatment and, in patients with AF, decreased anxiety about therapeutic decisions and increased willingness to accept treatment options.


Subject(s)
Atrial Fibrillation , Stroke , Humans , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Decision Making, Shared , Anxiety/prevention & control , Anticoagulants/therapeutic use , Outpatients , Stroke/prevention & control
15.
Eur J Med Chem ; 258: 115583, 2023 Oct 05.
Article in English | MEDLINE | ID: mdl-37393792

ABSTRACT

Down-regulation of Cisd2 in the liver has been implicated in the development of nonalcoholic fatty liver disease (NAFLD) and increasing the level of Cisd2 is therefore a potential therapeutic approach to this group of diseases. Herein, we describe the design, synthesis, and biological evaluation of a series of Cisd2 activators, all thiophene analogs, based on a hit obtained using two-stage screening and prepared via either the Gewald reaction or by intramolecular aldol-type condensation of an N,S-acetal. Metabolic stability studies of the resulting potent Cisd2 activators suggest that thiophenes 4q and 6 are suitable for in vivo studies. The results from studies on 4q-treated and 6-treated Cisd2hKO-het mice, which carry a heterozygous hepatocyte-specific Cisd2 knockout, confirm that (1) there is a correlation between Cisd2 levels and NAFLD and (2) these compounds have the ability to prevent, without detectable toxicity, the development and progression of NAFLD.


Subject(s)
Non-alcoholic Fatty Liver Disease , Animals , Mice , Down-Regulation , Hepatocytes/metabolism , Liver/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Thiophenes/pharmacology , Thiophenes/therapeutic use
16.
Pharmaceutics ; 15(7)2023 Jul 17.
Article in English | MEDLINE | ID: mdl-37514151

ABSTRACT

Large-area craniofacial defects remain a challenge for orthopaedists, hastening the need to develop a facile and safe tissue engineering strategy; osteoconductive material and a combination of optimal growth factors and microenvironment should be considered. Faced with the unmet need, we propose that abundant cytokines and chemokines can be secreted from the bone defect, provoking the infiltration of endogenous stem cells to assist bone regeneration. We can provide a potent mRNA medicine cocktail to promptly initiate the formation of bone templates, osteogenesis, and subsequent bone matrix deposition via endochondral ossification, which may retard rapid fibroblast infiltration and prevent the formation of atrophic non-union. We explored the mutual interaction of BMP2 and TGFß3 mRNA, both potent chondrogenic factors, on inducing endochondral ossification; examined the influence of in vitro the transcribed polyA tail length on mRNA stability; prepared mRNA nanomedicine using a PEGylated polyaspartamide block copolymer loaded in a gelatin sponge and grafted in a critical-sized calvarial defect; and evaluated bone regeneration using histological and µCT examination. The BMP2 and TGFß3 composite mRNA nanomedicine resulted in over 10-fold new bone volume (BV) regeneration in 8 weeks than the BMP2 mRNA nanomedicine administration alone, demonstrating that the TGFß3 mRNA nanomedicine synergistically enhances the bone's formation capability, which is induced by BMP2 mRNA nanomedicine. Our data demonstrated that mRNA-medicine-mediated endochondral ossification provides an alternative cell-free tissue engineering methodology for guiding craniofacial defect healing.

17.
Front Cardiovasc Med ; 10: 1135230, 2023.
Article in English | MEDLINE | ID: mdl-37252115

ABSTRACT

Background: Catheter ablation (CA) is a treatment strategy for atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). We investigated the electrophysiological characteristics of recurrence in a tertiary referral center and compared long-term clinical outcomes after CA therapy with patients who did not undergo CA. Methods: Patients with HCM and AF who underwent CA (group 1, n = 60) or pharmacological treatment (group 2, n = 298) between 2006 and 2021 were enrolled in this study. The baseline characteristics and electrophysiological characteristics of group 1 patients were examined to elucidate the reason for the recurrence of AF after CA therapy. The clinical results of the patients in Group 1 and Group 2 were compared using a propensity score (PS)-matched method. Results: The most common cause of recurrence was pulmonary vein reconnection (86.5%), followed by non-pulmonary vein triggers (40.5%), cavotricuspid isthmus flutter (29.7%), and atypical flutter (24.3%). Thyroid disease (HR, 14.713; P < 0.01), diabetes (HR, 3.074; P = 0.03), and non-paroxysmal AF (HR, 4.012; P = 0.01); these factors independently predicted recurrence. After the first recurrence, patients who underwent repeat CA showed a better arrhythmia-free state (74.1%) than those who underwent drug escalation therapy (29.4%, P < 0.01). After matching, PS-group 1 patients showed significantly better outcomes in all-cause mortality, heart failure hospitalization, and left atrial reverse remodeling than PS-group 2 patients. Conclusions: Patients who underwent CA showed better clinical outcomes than those who underwent drug therapy. The main predictors of recurrence were thyroid disease, diabetes, and non-paroxysmal AF.

18.
J Cardiovasc Electrophysiol ; 34(5): 1230-1240, 2023 05.
Article in English | MEDLINE | ID: mdl-37061887

ABSTRACT

INTRODUCTION: Ventricular arrhythmia (VA) commonly originate from the left ventricular summit (LVS) and results in left ventricular (LV) dysfunction in some patients; however, factors related to LV cardiomyopathy have not been well elucidated. Therefore, this study aimed to investigate the risk factors for LV cardiomyopathy and the outcomes of patients with LVS VA. METHODS: Between 2013 and 2018, a total of 139 patients (60.7% men; mean age 53.2 ± 13.9 years old) underwent catheter ablation for LVS VA in two centers. Detailed patient demographics, electrocardiograms, electrophysiological characteristics, and clinical outcomes were analyzed. LV cardiomyopathy was defined as left ventricular ejection fraction (LVEF) <50%. RESULTS: Acute procedural success was achieved in 92.8% of patients. There were 40 patients (28.8%) with LV cardiomyopathy, and the mean LVEF improved from 37.5 ± 9.3% to 48.5 ± 10.2% after ablation (p < .001). After multivariate analysis, the independent factors of LV dysfunction were wider QRS duration (QRSd) of the VA (odds ratio [OR] 1.02; 95% confidence interval [CI]: 1.00-1.04; p = .046) and the absolute earliest activation time discrepancy (AEAD) between epicardium and endocardium (OR 1.05; 95% CI: 1.00-1.09; p = .048). After ablation, the LV function was completely recovered in 20 patients (50%). The factors for LV dysfunction without recovery included wider premature ventricular complex (PVC) QRSd (OR 1.09; 95% CI: 1.02-1.17; p = .012) and poorer LVEF (OR 0.85; 95% CI: 0.74-0.97; p = .020). CONCLUSION: In patients with VA from the LVS, PVC QRSd and AEAD are factors associated with deteriorating LV systolic function. Catheter ablation can reverse LV remodeling. Narrower QRSd and better LVEF are associated with better recovery of LV function after ablation.


Subject(s)
Cardiomyopathies , Catheter Ablation , Ventricular Dysfunction, Left , Ventricular Premature Complexes , Male , Humans , Adult , Middle Aged , Aged , Female , Ventricular Function, Left , Stroke Volume/physiology , Ventricular Premature Complexes/diagnosis , Ventricular Premature Complexes/surgery , Ventricular Premature Complexes/complications , Treatment Outcome , Electrocardiography/methods , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Dysfunction, Left/etiology , Catheter Ablation/adverse effects , Catheter Ablation/methods
19.
PLoS One ; 18(4): e0282943, 2023.
Article in English | MEDLINE | ID: mdl-37079563

ABSTRACT

BACKGROUND: Amiodarone is commonly used during therapeutic hypothermia (TH) following cardiac arrest due to ventricular arrhythmias. However, electrophysiological changes and proarrhythmic risk after amiodarone treatment have not yet been explored in TH. METHODS: Epicardial high-density bi-ventricular mapping was performed in pigs under baseline temperature (BT), TH (32-34°C), and amiodarone treatment during TH. The total activation time (TAT), conduction velocity (CV), local electrogram (LE) duration, and wavefront propagation from pre-specified segments were analyzed during sinus rhythm (SR) or right ventricular (RV) pacing (RVP), along with tissue expression of connexin 43. The vulnerability to ventricular arrhythmias was assessed. RESULTS: Compared to BT, TH increased the global TAT, decreased the CV, and generated heterogeneous electrical substrate during SR and RVP. During TH, the CV reduction and LE duration prolongation were greater in the anterior mid RV than in the other areas, which changed the wavefront propagation in all animals. Compared to TH alone, amiodarone treatment during TH further increased the TAT and LE duration and decreased the CV. Heterogeneous conduction was partially attenuated after amiodarone treatment. After TH and amiodarone treatment, the connexin 43 expression in the anterior mid RV was lower than that in the other areas, compatible with the heterogeneous CV reduction. The animals under TH and amiodarone treatment had a higher incidence of inducible ventricular arrhythmias than those under BT or TH without amiodarone. CONCLUSION: Electrical heterogeneity during amiodarone treatment and TH was associated with vulnerability to ventricular arrhythmias.


Subject(s)
Amiodarone , Hypothermia, Induced , Animals , Swine , Amiodarone/adverse effects , Connexin 43/metabolism , Arrhythmias, Cardiac , Heart Ventricles , Hypothermia, Induced/adverse effects
20.
Europace ; 25(5)2023 05 19.
Article in English | MEDLINE | ID: mdl-37097046

ABSTRACT

AIMS: This study investigated the epidemiological characteristics of new-onset dementia in patients with atrial fibrillation (AF) and the association of catheter ablation with different subtypes of dementia. METHODS AND RESULTS: We conducted a population-based, retrospective cohort study using data from the Taiwan National Health Insurance Research Database. In total, 136 774 patients without a history of dementia were selected after 1:1 propensity score matching based on age (with AF vs. without AF). A competing risk model was used to investigate the three subtypes of dementia: Alzheimer's disease, vascular dementia, and other/mixed dementia. Inverse probability of treatment weighting (IPTW) was performed to minimize the impact on dementia risk due to the imbalanced baseline characteristics. After a median follow-up period of 6.6 years, 8704 events of new-onset dementia occurred. Among all AF patients developing dementia, 73% were classified as having Alzheimer's disease, 16% as having vascular dementia, and 11% as having other/mixed dementia. The cumulative incidence of dementia in AF patients was higher than those without AF (log-rank test: P < 0.001 for both before and after IPTW). In patients with AF undergoing catheter ablation, the total dementia risk decreased significantly [P = 0.015, hazard ratio (HR): 0.74, 95% confidence interval (CI): 0.58-0.94] after multivariable adjustment, but not for the subtype of vascular dementia (P = 0.59, HR: 0.86, 95% CI: 0.49-1.50). CONCLUSION: Patients with AF have a higher incidence of all types of dementia, including Alzheimer's disease, vascular dementia, and a mixed type of dementia. Alzheimer's disease is less likely to occur in patients with AF undergoing catheter ablation.


Subject(s)
Alzheimer Disease , Atrial Fibrillation , Catheter Ablation , Dementia, Vascular , Humans , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/surgery , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Alzheimer Disease/complications , Dementia, Vascular/complications , Dementia, Vascular/surgery , Retrospective Studies , Risk Reduction Behavior , Catheter Ablation/adverse effects , Risk Factors , Treatment Outcome , Follow-Up Studies , Recurrence
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