Accumulating evidence suggests that thiazolidinediones (TZDs) may exert protective effects in atrial fibrillation (AF). The present meta-analysis investigated the association between TZD use and the incidence of AF in diabetic patients. Electronic databases were searched until December 2016. Of the 346 initially identified records, 3 randomized clinical trials (RCTs) and 4 observational studies with 130,854 diabetic patients were included in the final analysis. Pooled analysis of the included studies demonstrated that patients treated with TZDs had approximately 30% lower risk of developing AF compared to controls [odds ratio (OR): 0.73, 95% confidence interval (CI): 0.62 to 0.87, p = 0.0003]. This association was consistently observed for both new onset AF (OR =0.77, p = 0.002) and recurrent AF (OR =0.41, p = 0.002), pioglitazone use (OR =0.56, p = 0.04) but not rosiglitazone use (OR =0.78, p = 0.12). The association between TZD use and AF incidence was not significant in the pooled analysis of three RCTs (OR =0.77, 95% CI = 0.53–1.12, p = 0.17), but was significantly in the pooled analysis of the four observational studies (OR =0.71, p = 0.0003). This meta-analysis suggests that TZDs may confer protection against AF in the setting of diabetes mellitus (DM). This class of drugs can be used as upstream therapy for DM patients to prevent the development of AF. Further large-scale RCTs are needed to determine whether TZDs use could prevent AF in the setting of DM.

/pdf/thiazolidinedione-use-and-atrial-fibrillation-in-diabetic-hn5ojekn3o.pdf

Thiazolidinedione use and atrial fibrillation in diabetic patients: a meta-analysis.

Since 1985, the thiazolidinedione pioglitazone has been widely used as an insulin sensitizer drug for type 2 diabetes mellitus (T2DM). Although fluid retention was early recognized as a safety concern, data from clinical trials have not provided conclusive evidence for a benefit or a harm on cardiac function, leaving the question unanswered. We reviewed the available evidence encompassing both in vitro and in vivo studies in tissues, isolated organs, animals and humans, including the evidence generated by major clinical trials. Despite the increased risk of hospitalization for heart failure due to fluid retention, pioglitazone is consistently associated with reduced risk of myocardial infarction and ischemic stroke both in primary and secondary prevention, without any proven direct harm on the myocardium. Moreover, it reduces atherosclerosis progression, in-stent restenosis after coronary stent implantation, progression rate from persistent to permanent atrial fibrillation, and reablation rate in diabetic patients with paroxysmal atrial fibrillation after catheter ablation. In fact, human and animal studies consistently report direct beneficial effects on cardiomyocytes electrophysiology, energetic metabolism, ischemia–reperfusion injury, cardiac remodeling, neurohormonal activation, pulmonary circulation and biventricular systo-diastolic functions. The mechanisms involved may rely either on anti-remodeling properties (endothelium protective, inflammation-modulating, anti-proliferative and anti-fibrotic properties) and/or on metabolic (adipose tissue metabolism, increased HDL cholesterol) and neurohormonal (renin–angiotensin–aldosterone system, sympathetic nervous system, and adiponectin) modulation of the cardiovascular system. With appropriate prescription and titration, pioglitazone remains a useful tool in the arsenal of the clinical diabetologist.

/pdf/rethinking-pioglitazone-as-a-cardioprotective-agent-a-new-zy8ej3a6ys.pdf

Rethinking pioglitazone as a cardioprotective agent: a new perspective on an overlooked drug.

Peroxisome proliferator-activated receptor (PPAR)-γ is involved in both normal physiological processes and pathology of various diseases. The purpose of this study was to explore the function and underlying mechanisms of PPAR-γ in rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) proliferation and migration. In the present study, we found PPAR-γ expression was remarkably reduced in RA synovium patient compare with OA and normal, as well as it was low-expression in Adjuvant-induced arthritis (AA). Moreover, inhibition PPAR-γ expression by T0070907 (12.5 μM) or PPAR-γ siRNA could promote FLSs proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, except for TIPM-1. These date indicate that up-regulation of PPAR-γ may play a critical role in RA FLSs. Interestingly, co-incubation FLSs with Pioditazone (25 μM) and over expression vector with pEGFP-N1-PPAR-γ reduced proliferation and expressions of c-Myc, Cyclin D1, MMP-1, and MMP-9 in AA FLSs, besides TIMP-1. Further study indicates that PPAR-γ may induce activation Wnt/β-catenin signaling. In short, these results indicate that PPAR-γ may play a pivotal role during FLSs activation and activation of Wnt/β-catenin signaling pathway.

/pdf/functional-role-of-ppar-g-on-the-proliferation-and-migration-z02sgdg5yo.pdf

Functional role of PPAR-γ on the proliferation and migration of fibroblast-like synoviocytes in rheumatoid arthritis

Purpose Cardiac radioablation (CR), a new treatment for cardiac arrhythmias such as ventricular tachycardia and atrial fibrillation, has had promising clinical outcomes to date. There is consequent desire for rapid clinical adoption. However, CR presents unique challenges to radiation therapy, and it is paramount that clinical adoption be performed safely and effectively. Recent reviews comprehensively detail patient selection, clinical history, treatment outcomes, and treatment toxicities but only briefly mention the technical aspects of CR. To address this knowledge gap, this review collates currently available knowledge regarding CR technology choice and procedural details to help inform and guide clinics considering implementing their own CR program, to aid technique standardization, and to highlight areas that require further development or verification. Methods and Materials Original preclinical and clinical scientific articles that sufficiently detailed CR technical aspects, including pretreatment electrophysiology and imaging, motion analysis and management techniques, treatment planning, and/or treatment delivery, were identified within a comprehensive literature search. Results Nineteen preclinical and 18 clinical scientific articles sufficiently detailed the technical aspects of CR treatment deliveries on live subjects. The technical aspects of these scientific articles were diverse: Preclinical treatments have been performed with brachytherapy, photons, protons, and carbon ions, and clinical treatments have been performed with photons using conventional, robotic, and magnetic resonance imaging guided systems. Other technical aspects demonstrated similar variability. Conclusions This review summarizes the technical aspects and procedural details of preclinical and clinical CR treatment deliveries and highlights the complexity and current variability of CR. There is need for standardized procedural reporting to aid multicenter and multiplatform evaluation and potential for significant technological improvements in imaging, planning, delivery, and monitoring to maximize the clinical outcomes for selected patients with arrhythmia.

A Review of Cardiac Radioablation (CR) for Arrhythmias: Procedures, Technology, and Future Opportunities.

Pulmonary vein isolation using robotic radiosurgery system CyberKnife is a new non-invasive treatment of atrial fibrillation, currently in clinical phase. Robotic radiosurgical pulmonary vein isolation (RRPVI) uses stereotactic, non-invasive (painless) pinpoint radiation energy delivery to a small, precise area to accomplish ablation. The purpose of this report is to describe the finding of an increase in the enhancement of the left atrium demonstrated with the use of cardiac magnetic resonance imaging using late gadolinium enhancement (LGE-CMR) as a result of RRPVI in the first case in the world in humans using CyberKnife as a treatment for paroxysmal atrial fibrillation (PAF).

/pdf/late-gadolinium-enhancement-cardiac-magnetic-resonance-4n3s7ebvbq.pdf

Late Gadolinium Enhancement Cardiac Magnetic Resonance Imaging Post-robotic Radiosurgical Pulmonary Vein Isolation (RRPVI): First Case in the World

BACKGROUND It has been demonstrated that atrial electrical remodeling contributes toward atrial fibrillation (AF) maintenance, and that angiotensin II (AngII) is involved in the pathogenesis of atrial electrical remodeling. Peroxisome proliferator activated receptor-γ (PPAR-γ) agonists have been shown to inhibit atrial electrical remodeling, but the underlying mechanisms are poorly understood. In the present study we investigated the regulating effects of PPAR-g agonist on AngII-induced potassium channel remodeling in atrial myocytes. MATERIAL/METHODS Whole-cell patch-clamp technique was used to record transient outward potassium current (Ito), ultra-rapid delayed rectifier potassium (Ikur), and inward rectifier potassium current (Ik1). Real-time PCR was used to assess potassium channel subunit mRNA expression. RESULTS Compared with the control group, AngII reduced Ito and Ikur current density as well as amplified Ik1 current density, which were partially prevented by pioglitazone. Furthermore, pioglitazone alleviated the downregulation of Ito subunit (Kv 4.2) and Ikur subunit (Kv 1.5), as well as the upregulation of Ik1 subunit (Kir 2.1 and Kir 2.2) mRNA expression stimulated by AngII. CONCLUSIONS These results suggest that pioglitazone exhibits a beneficial effect on AngII-induced potassium channel remodeling. PPAR-γ agonists may be potentially effective up-stream therapies for AF.

Pioglitazone Improves Potassium Channel Remodeling Induced by Angiotensin II in Atrial Myocytes

PPARγ agonist use and recurrence of atrial fibrillation after successful electrical cardioversion

Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice. Catheter ablation is now a recognized treatment for those with symptomatic AF refractory to drug therapy. Innovations in magnetic resonance imaging (MRI) have empowered clinicians to improve ablation efficacy while reducing the risk of complications. It is demonstrated that late gadolinium enhancement MRI has additional advantages over modalities such as echocardiography and computed tomography, due to its ability to assess the structural remodeling directly. As a result, MRI has become an indispensable imaging tool to personalize the AF ablation strategy, assess the efficacy and potential complications of AF ablation, and guide the repeat procedure.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/clc.22360

The value of magnetic resonance imaging in catheter ablation of atrial fibrillation.

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Pioglitazone Improves Potassium Channel Remodeling Induced by Angiotensin II in Atrial Myocytes

PPARγ agonist use and recurrence of atrial fibrillation after successful electrical cardioversion

The value of magnetic resonance imaging in catheter ablation of atrial fibrillation.