Mechanisms of action behind the protective effects of proactive esophageal cooling during radiofrequency catheter ablation in the left atrium.

Proactive esophageal cooling for the purpose of reducing the likelihood of ablation-related esophageal injury resulting from radiofrequency (RF) cardiac ablation procedures is increasingly being used and has been Food and Drug Administration cleared as a protective strategy during left atrial RF ablation for the treatment of atrial fibrillation. In this review, we examine the evidence supporting the use of proactive esophageal cooling and the potential mechanisms of action that reduce the likelihood of atrioesophageal fistula (AEF) formation. Although the pathophysiology behind AEF formation after thermal injury from RF ablation is not well studied, a robust literature on fistula formation in other conditions (eg, Crohn disease, cancer, and trauma) exists and the relationship to AEF formation is investigated in this review. Likewise, we examine the abundant data in the surgical literature on burn and thermal injury progression as well as the acute and chronic mitigating effects of cooling. We discuss the relationship of these data and maladaptive healing mechanisms to the well-recognized postablation pathophysiological effects after RF ablation. Finally, we review additional important considerations such as patient selection, clinical workflow, and implementation strategies for proactive esophageal cooling.

A narrative review of hybrid ablation for persistent and longstanding persistent atrial fibrillation.

Atrial fibrillation is the most common sustained arrhythmia and is characterized by rapid and irregular atrial activation with loss of atrial contraction. There has been a significant evolution of treatments over the past 30 years. Initially, cardiac surgeons developed approaches via sternotomy with superior efficacy, however early iterations of the procedure were associated with prolonged recovery time and frequent need for pacemaker placement. The current surgical approach to the maze procedure via sternotomy yields excellent efficacy and is a Class 1 recommendation for patients with atrial fibrillation undergoing a concomitant procedure. Several years following the initial development of the surgical maze procedure, cardiac electrophysiologists developed less invasive, however less efficacious catheter ablation options by percutaneous approach. Both the surgical and transcatheter approaches have their advantages and disadvantages with varying risks of complications and efficacy. Through the combination of expertise of cardiac surgeons paired with the electrophysiology team, a hybrid ablation procedure has been developed offering an increased efficacy with a less-invasive approach than the current gold standard treatment of Cox-maze IV procedure. This review will discuss the hybrid ablation procedure, review recent associated clinical trials, and discuss advantages and challenges associated with this multidisciplinary approach for management of patients with AF.

ANGPTL4 deficiency in haematopoietic cells promotes monocyte expansion and atherosclerosis progression.

Lipid accumulation in macrophages has profound effects on macrophage gene expression and contributes to the development of atherosclerosis. Here, we report that angiopoietin-like protein 4 (ANGPTL4) is the most highly upregulated gene in foamy macrophages and it's absence in haematopoietic cells results in larger atherosclerotic plaques, characterized by bigger necrotic core areas and increased macrophage apoptosis. Furthermore, hyperlipidemic mice deficient in haematopoietic ANGPTL4 have higher blood leukocyte counts, which is associated with an increase in the common myeloid progenitor (CMP) population. ANGPTL4-deficient CMPs have higher lipid raft content, are more proliferative and less apoptotic compared with the wild-type (WT) CMPs. Finally, we observe that ANGPTL4 deficiency in macrophages promotes foam cell formation by enhancing CD36 expression and reducing ABCA1 localization in the cell surface. Altogether, these findings demonstrate that haematopoietic ANGPTL4 deficiency increases atherogenesis through regulating myeloid progenitor cell expansion and differentiation, foam cell formation and vascular inflammation.

Meta-Analysis of the Relation of Baseline Right Ventricular Function to Response to Cardiac Resynchronization Therapy.

Right ventricular (RV) dysfunction has been associated with adverse clinical outcomes in patients with heart failure (HF). Cardiac resynchronization therapy (CRT) improves left ventricular (LV) size and function in patients with markedly abnormal electrocardiogram QRS duration. However, relation of baseline RV function with response to CRT has not been well described. In this study, we aim to investigate the relation of baseline RV function with response to CRT as assessed by change in LV ejection fraction (EF). A systematic search of studies published from 1966 to May 31, 2015 was conducted using PubMed, CINAHL, Cochrane CENTRAL, and the Web of Science databases. Studies were included if they have reported (1) parameters of baseline RV function (tricuspid annular plane systolic excursion [TAPSE] or RVEF or RV basal strain or RV fractional area change [FAC]) and (2) LVEF before and after CRT. Random-effects metaregression was used to evaluate the effect of baseline RV function parameters and change in LVEF. Sixteen studies (n = 1,764) were selected for final analysis. Random-effects metaregression analysis showed no significant association between the magnitude of the difference in EF before and after CRT with baseline TAPSE (ß = 0.005, p = 0.989); baseline RVEF (ß = 0.270, p = 0.493); baseline RVFAC (ß = -0.367, p = 0.06); baseline basal strain (ß = -0.342, p = 0.462) after a mean follow-up period of 10.5 months. In conclusion, baseline RV function as assessed by TAPSE, FAC, basal strain, or RVEF does not determine response to CRT as assessed by change in LVEF.

Early Hemodynamic Changes during Head-Up Tilt Table Testing Can Predict a Neurocardiogenic Response in an African-American Patient Population.

BACKGROUND: Head-up tilt table testing (HUTT) is time-consuming and associated with increased patient morbidity. Hemodynamic changes that occur during the early phase of HUTT may be predictive of neurocardiogenic syncope. METHODS: A retrospective chart review was performed in 119 consecutive African Americans ( 57 ± 19) who underwent HUTT for evaluation of syncope of unknown etiology. Positive responses were defined as the development of symptoms linked with a systolic blood pressure (BP) <90 mm Hg, heart rate <50 b.p.m. or sinus arrest >3 s. Hemodynamic variables during the passive phase of HUTT were analyzed and results were then classified as a function of various predictors. RESULTS: Sixty-two subjects (52%) had positive HUTT, and 57 (48%) had negative HUTT. Early changes in BP variables from baseline significantly predicted HUTT responses (p < 0.05). There was also a significant interaction between age and BP. An algorithm based on age and BP was developed which had positive and negative predictive values of 67.7 and 93%, respectively, with an accuracy of 79.8%. CONCLUSION: A novel algorithm utilizing the patients' age and changes in both systolic and diastolic BP during the early phase of HUTT enables the prediction of HUTT results without the use of vasoactive stimulation, allowing for rapid diagnosis, decreased patient morbidity and reduction in costs.

The effects of ischemia with and without remote conditioning on hyperemia induced decline in carotid-radial pulse wave velocity.

Ischemic conditioning has long held promise for preventing ischemic-reperfusion (I-R) injury. Although a number of studies have evaluated the effects of brief repeated episodes of ischemia before a prolonged ischemic episode on the cardiovascular system using clinical endpoints, more sensitive techniques by which to measure its effects are lacking. Since endothelial function is sensitive to I-R injury, flow mediated dilation of the brachial artery has been proposed for this purpose, but has significant limitations. Hyperemia normally decreases carotid to radial pulse wave velocity (PWV). Accordingly, we sought to determine the effects of I-R injury and ischemic conditioning on the hyperemic change (Δ) in PWV. We induced hyperemia by release of arterial cuff occlusion before and after ipsilateral arm I-R injury (7.5min occlusion) in 25 healthy males, age 29±6 years. The protocol was repeated on 2 occasions in combination with either pre- or post- conditioning stimuli (3× 30s contralateral arm occlusions). Hyperemia resulted in a significant decrease (-13.7%, p<.001) before but not after prolonged ischemia (-0.88%, p=0.40). I-R along with either pre- or post-ischemic conditioning restored the PWV decline (pre: -11.0%, p<0.001; post: -9.9%, p<0.001). In conclusion, 7.5min ischemia blunts the normal PWV decline produced by hyperemia. Remote pre- and post-conditioning restores this response. This technique may be useful for the assessment of novel treatment strategies and mechanisms underlying remote pre- and post-ischemic conditioning in protecting the cardiovascular system.

MicroRNA-758 regulates cholesterol efflux through posttranscriptional repression of ATP-binding cassette transporter A1.

OBJECTIVE: The ATP-binding cassette transporter A1 (ABCA1) is a major regulator of macrophage cholesterol efflux and protects cells from excess intracellular cholesterol accumulation; however, the mechanism involved in posttranscriptional regulation of ABCA1 is poorly understood. We previously showed that microRNA-33 (miR-33) is 1 regulator. Here, we investigated the potential contribution of other microRNAs (miRNAs) to posttranscriptional regulation of ABCA1 and macrophage cholesterol efflux. METHODS AND RESULTS: We performed a bioinformatic analysis for identifying miRNA target prediction sites in ABCA1 gene and an unbiased genome-wide screen to identify miRNAs modulated by cholesterol excess in mouse peritoneal macrophages. Quantitative real-time reverse transcription-polymerase chain reaction confirmed that miR-758 is repressed in cholesterol-loaded macrophages. Under physiological conditions, high dietary fat excess in mice repressed miR-758 both in peritoneal macrophages and, to a lesser extent, in the liver. In mouse and human cells in vitro, miR-758 repressed the expression of ABCA1, and conversely, the inhibition of this miRNA by using anti-miR-758 increased ABCA1 expression. In mouse cells, miR-758 reduced cellular cholesterol efflux to apolipoprotein A1 (apoA1), and anti-miR-758 increased it. miR-758 directly targets the 3'-untranslated region of Abca1 as assessed by 3'-untranslated region luciferase reporter assays. Interestingly, miR-758 is highly expressed in the brain, where it also targets several genes involved in neurological functions, including Slc38a1, Ntm, Epha7, and Mytl1. CONCLUSION: We identified miR-758 as a novel miRNA that posttranscriptionally controls ABCA1 levels in different cells and regulates macrophage cellular cholesterol efflux to apoA1, opening new avenues to increase apoA1 and raise high-density lipoprotein levels.

miR-33a/b contribute to the regulation of fatty acid metabolism and insulin signaling.

Cellular imbalances of cholesterol and fatty acid metabolism result in pathological processes, including atherosclerosis and metabolic syndrome. Recent work from our group and others has shown that the intronic microRNAs hsa-miR-33a and hsa-miR-33b are located within the sterol regulatory element-binding protein-2 and -1 genes, respectively, and regulate cholesterol homeostasis in concert with their host genes. Here, we show that miR-33a and -b also regulate genes involved in fatty acid metabolism and insulin signaling. miR-33a and -b target key enzymes involved in the regulation of fatty acid oxidation, including carnitine O-octaniltransferase, carnitine palmitoyltransferase 1A, hydroxyacyl-CoA-dehydrogenase, Sirtuin 6 (SIRT6), and AMP kinase subunit-α. Moreover, miR-33a and -b also target the insulin receptor substrate 2, an essential component of the insulin-signaling pathway in the liver. Overexpression of miR-33a and -b reduces both fatty acid oxidation and insulin signaling in hepatic cell lines, whereas inhibition of endogenous miR-33a and -b increases these two metabolic pathways. Together, these data establish that miR-33a and -b regulate pathways controlling three of the risk factors of metabolic syndrome, namely levels of HDL, triglycerides, and insulin signaling, and suggest that inhibitors of miR-33a and -b may be useful in the treatment of this growing health concern.