Catheter Ablation of Atrial Fibrillation: Where Are We?

Atrial fibrillation (AF) is the commonest cardiac arrhythmia, with significant morbidity and mortality. More than half of patients with AF are still symptomatic despite adequate anticoagulation and rate control. If antiarrhythmic drugs are ineffective or poorly tolerated, AF patients are then typically treated with catheter ablation to restore sinus rhythm. In the past 20 years, AF ablation has developed from a specialized, experimental procedure into a common treatment in the cardiovascular field. Various ablation techniques and mapping technologies have been described and are continuing to evolve for increased safety and efficacy. An incomplete list of such techniques and technologies would include focal and segmental, circumferential and linear, complex fractionated atrial electrogram, ganglionated plexus, focal impulse and rotor modulation, body surface potential mapping–guided, real-time MRI–guided, cryoballoon, visually guided laser balloon, radiofrequency hot balloon, contact force sensing catheter, multielectrode catheter, and hybrid ablations. This review examines the history of invasive AF treatment and its evolution into catheter ablation but mainly focuses on the discussion of various ablation techniques and technologies leading to our current understanding of the ablation therapy of this most common arrhythmia

Percutaneous Left Atrial Appendage Occlusion Therapy: Past, Present, and Future

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is increasing in incidence and prevalence worldwide. AF significantly increases the risk of intracardiac thrombus formation and, if left untreated, ischemic stroke. In patients with nonvalvular AF (NVAF), the left atrial appendage (LAA) has been determined to be the source of thrombus development in 91% to 99% of cases. In this regard, oral anticoagulants (OACs) have become the standard treatment for stroke prevention in most patients with AF; however, OACs are associated with a risk of bleeding complications, and their efficacy depends on optimal patient compliance. Among alternative approaches to embolic stroke prevention, surgical LAA excision for stroke prevention for valvular AF was attempted as early as the late 1940s. LAA excision remains recommended in surgical guidelines for patients with NVAF requiring open-heart coronary bypass or valvular replacement/repair surgeries. However, owing to the traumatic/invasive nature and suboptimal outcomes of conventional surgical LAA intervention, clinical application of this approach is limited in current cardiology practice. Percutaneous LAA occlusion (LAAO) is increasingly being performed as an alternative to OAC for stroke prevention, particularly in patients with elevated bleeding risk. Substantial progress has been made in percutaneous LAAO therapy since its inception approximately 20 years ago. This article systematically reviews the literature leading to the development of LAAO and the evidence-based clinical experience supporting the application of this treatment strategy for NVAF, with a focus on recently published critical evaluations of US FDA and CE mark approved LAAO devices. Future perspectives regarding knowledge and technology gaps are also discussed, recognizing the many ongoing clinical trials that are likely to be transformative and the critical unanswered questions regarding LAAO therapy

CLIP-KD: An Empirical Study of Distilling CLIP Models

CLIP has become a promising language-supervised visual pre-training framework and achieves excellent performance over a wide range of tasks. This paper aims to distill small CLIP models supervised by a large teacher CLIP model. We propose several distillation strategies, including relation, feature, gradient and contrastive paradigm, to examine the impact on CLIP distillation. We show that the simplest feature mimicry with MSE loss performs best. Moreover, interactive contrastive learning and relation-based distillation are also critical in performance improvement. We apply the unified method to distill several student networks trained on 15 million (image, text) pairs. Distillation improves the student CLIP models consistently over zero-shot ImageNet classification and cross-modal retrieval benchmarks. We hope our empirical study will become an important baseline for future CLIP distillation research. The code is available at \url{https://github.com/winycg/CLIP-KD}

A comparative study of discriminating human heart failure etiology using gene expression profiles

BACKGROUND: Human heart failure is a complex disease that manifests from multiple genetic and environmental factors. Although ischemic and non-ischemic heart disease present clinically with many similar decreases in ventricular function, emerging work suggests that they are distinct diseases with different responses to therapy. The ability to distinguish between ischemic and non-ischemic heart failure may be essential to guide appropriate therapy and determine prognosis for successful treatment. In this paper we consider discriminating the etiologies of heart failure using gene expression libraries from two separate institutions. RESULTS: We apply five new statistical methods, including partial least squares, penalized partial least squares, LASSO, nearest shrunken centroids and random forest, to two real datasets and compare their performance for multiclass classification. It is found that the five statistical methods perform similarly on each of the two datasets: it is difficult to correctly distinguish the etiologies of heart failure in one dataset whereas it is easy for the other one. In a simulation study, it is confirmed that the five methods tend to have close performance, though the random forest seems to have a slight edge. CONCLUSIONS: For some gene expression data, several recently developed discriminant methods may perform similarly. More importantly, one must remain cautious when assessing the discriminating performance using gene expression profiles based on a small dataset; our analysis suggests the importance of utilizing multiple or larger datasets

Five-Year Outcomes and Cardiac Remodeling Following Left Atrial Appendage Occlusion

Purpose: LAAO has been an alternative therapy to oral anticoagulants (OACs) for stroke prophylaxis in patients with nonvalvular atrial fibrillation (NVAF) with elevated CHA2DS2-Vasc score, but the long-term outcomes of LAAO and its impacts on cardiac electrical and mechanical remodeling remain to be learned. We aimed to describe the impact of left atrial appendage occlusion (LAAO) on atrial remodeling and cardiovascular outcomes within 5-year follow-up. Patients and methods: A total of 107 patients with nonvalvular atrial fibrillation (NVAF) undergoing LAAO in the Shanghai Tenth People's Hospital between January 2014 and July 2017 were included. All participants were followed for ECG, transthoracic echocardiography (TTE), and clinical outcomes (including cardiovascular death, heart failure, ischemic stroke/systemic embolism, and pericardial effusion) at 6 and 12 months, and thereafter every 12 months after LAAO discharge until 5 years. Results: After LAAO, the left atrial diameter significantly increased at 6 months (48.6 ± 6.7 vs 46.5 ± 7.0 mm); heart rate decreased immediately after the procedure (78.5 ± 14.7 vs 85.3 ± 21.7 bpm) when compared with the pre-procedure level. The QTc interval prolongated to the highest value of 460.7 ± 46.8 ms at 6 months (pre-procedure level of 433.7±49.0 ms). All these changes return to the pre-procedure level within the follow-up. For clinical outcomes, 51 patients suffered the composite of cardiovascular death (n=4, 3.7%), heart failure (n=25, 23.4%), ischemic stroke/systemic embolism (n=22, 20.6%), and pericardial effusion (n=26, 26.2%). Conclusion: LAAO did not change ECG or TTE characteristics and nonprocedure-related pericardial effusion is common during long-term follow-up. Further studies are warranted to investigate the optimal time frame of anticoagulation in patients undergoing LAAO

Genome-Wide Association of Implantable Cardioverter-Defibrillator Activation With Life-Threatening Arrhythmias

OBJECTIVES: To identify genetic factors that would be predictive of individuals who require an implantable cardioverter-defibrillator (ICD), we conducted a genome-wide association study among individuals with an ICD who experienced a life-threatening arrhythmia (LTA; cases) vs. those who did not over at least a 3-year period (controls). BACKGROUND: Most individuals that receive implantable cardioverter-defibrillators never experience a life-threatening arrhythmia. Genetic factors may help identify who is most at risk. METHODS: Patients with an ICD and extended follow-up were recruited from 34 clinical sites with the goal of oversampling those who had experienced LTA, with a cumulative 607 cases and 297 controls included in the analysis. A total of 1,006 Caucasian patients were enrolled during a time period of 13 months. Arrhythmia status of 904 patients could be confirmed and their genomic data were included in the analysis. In this cohort, there were 704 males, 200 females, and the average age was 73.3 years. We genotyped DNA samples using the Illumina Human660 W Genotyping BeadChip and tested for association between genotype at common variants and the phenotype of having an LTA. RESULTS AND CONCLUSIONS: We did not find any associations reaching genome-wide significance, with the strongest association at chromosome 13, rs11856574 at P = 5×10⁻⁶. Loci previously implicated in phenotypes such as QT interval (measure of the time between the start of the Q wave and the end of the T wave as measured by electrocardiogram) were not found to be significantly associated with having an LTA. Although powered to detect such associations, we did not find common genetic variants of large effect associated with having a LTA in those of European descent. This indicates that common gene variants cannot be used at this time to guide ICD risk-stratification. TRIAL REGISTRATION: ClinicalTrials.gov NCT00664807

Functional Improvement of Regulatory T Cells From Rheumatoid Arthritis Subjects Induced by Capsular Polysaccharide Glucuronoxylomannogalactan

Objective: Regulatory T cells (Treg) play a critical role in the prevention of autoimmunity, and the suppressive activity of these cells is impaired in rheumatoid arthritis (RA). The aim of the present study was to investigate function and properties of Treg of RA patients in response to purified polysaccharide glucuronoxylomannogalactan (GXMGal). Methods: Flow cytometry and western blot analysis were used to investigate the frequency, function and properties of Treg cells. Results: GXMGal was able to: i) induce strong increase of FOXP3 on CD4+ T cells without affecting the number of CD4+CD25+FOXP3+ Treg cells with parallel increase in the percentage of non-conventional CD4+CD25-FOXP3+ Treg cells; ii) increase intracellular levels of TGF-beta1 in CD4+CD25-FOXP3+ Treg cells and of IL-10 in both CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells; iii) enhance the suppressive activity of CD4+CD25+FOXP3+ and CD4+CD25-FOXP3+ Treg cells in terms of inhibition of effector T cell activity and increased secretion of IL-10; iv) decrease Th1 response as demonstrated by inhibition of T-bet activation and down-regulation of IFN-gamma and IL-12p70 production; v) decrease Th17 differentiation by down-regulating pSTAT3 activation and IL-17A, IL-23, IL-21, IL-22 and IL-6 production. Conclusion: These data show that GXMGal improves Treg functions and increases the number and function of CD4+CD25-FOXP3+ Treg cells of RA patients. It is suggested that GXMGal may be potentially useful for restoring impaired Treg functions in autoimmune disorders and for developing Treg cell-based strategies for the treatment of these diseases

Percutaneous Left Atrial Appendage Occlusion Therapy: Evolution and Growing Evidence

Atrial fibrillation (AF) is the most common cardiac arrhythmia and if untreated, significantly increases both the risk of intracardiac thrombus formation and ischemic stroke. In patients with nonvalvular AF (NVAF), the left atrial appendage (LAA) has been estimated to be the source of thrombus development in 91% to 99% of cases. Consequently, oral anticoagulation (OAC) to provide stroke prevention has become the standard of care for most AF patients; however, OACs are associated with a risk of bleeding and their efficacy depends on optimal patient compliance. In terms of alternative approaches to preventing embolic events, surgical LAA excision was attempted as early as in the late 1940s in patients with valvular AF; LAA excision remains a recommendation in surgical guidelines for NVAF patients who need open-heart coronary bypass or valvular replacement/repair surgeries. However, due to its invasive nature surgical LAA intervention has limited clinical application in present cardiology practice. Percutaneous LAA occlusion (LAAO) is increasingly being performed as an alternative to OAC for stroke prevention; this is particularly the case in patients at increased bleeding risk. Substantial progress has been made in percutaneous LAAO therapy since its inception some twenty years ago. Herein we systematically review both the critical literature that led to the development of LAAO, and the increasing clinical evidence supporting the application of this treatment strategy in NVAF. To this end we focus on recently published critical evaluations of United States Food and Drug Administration (US FDA) and Conformité Européenne (Commercial Sale of Licensed Product in the EU) (CE-Mark) approved LAAO devices, summarize the current status of LAAO therapy, and discuss the future perspectives regarding the knowledge and technology gaps in this area by recognizing the potential contributions of many ongoing but likely transformative clinical trials