Effect of SGLT-2 inhibitors on arrhythmia events: insight from an updated secondary analysis of > 80,000 patients (the SGLT2i-Arrhythmias and Sudden Cardiac Death).

OBJECTIVE: We aimed to assess the effect of SGLT2i on arrhythmias by conducting a meta-analysis using data from randomized controlled trials(RCTs). BACKGROUND: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have shown cardioprotective effects via multiple mechanisms that may also contribute to decrease arrhythmias risk. METHODS: We searched in databases (PubMed, Embase, Cochrane Library, and clinicaltrials.gov) up to April 2023. RCTs comparing SGLT2i with placebo were included. The effects of SGLT2i on atrial fibrillation(AF), atrial flutter(AFL), composite AF/AFL, ventricular fibrillation(VF), ventricular tachycardia(VT), ventricular extrasystoles(VES), sudden cardiac death(SCD) and composite VF/VT/SCD were evaluated. RESULTS: 33 placebo-controlled RCTs were included, comprising 88,098 patients (48,585 in SGLT2i vs. 39,513 in placebo). The mean age was 64.9 ± 9.4 years, 63.0% were male. The mean follow-up was 1.4 ± 1.1 years. The pooled-results showed that SGLT2i was associated with a significantly lower risk of AF [risk ratio(RR): 0.88, 95% confidence interval(CI) 0.78-1.00, P = 0.04] and composite AF/AFL (RR: 0.86, 95%CI 0.77-0.96, P = 0.01). This favorable effect appeared to be substantially pronounced in patients with HFrEF, male gender, dapagliflozin, and > 1 year follow-up. For SCD, only in heart failure patients, SGLT2i were found to be associated with a borderline lower risk of SCD (RR: 0.67, P = 0.05). No significant effects of SGLT2i on other ventricular arrhythmic outcomes were found. CONCLUSIONS: SGLT2i lowers the risks of AF and AF/AFL, and this favorable effect appeared to be particularly pronounced in patients with HFrEF, male gender, dapagliflozin, and longer follow-up (> 1 year). SGLT2i lowers the risk of SCD only in heart failure patients.

Impact of high-power short-duration atrial fibrillation ablation technique on the incidence of silent cerebral embolism: a prospective randomized controlled study.

BACKGROUND: High-power short-duration (HPSD) ablation strategy has emerged as a popular approach for treating atrial fibrillation (AF), with shorter ablation time. The utilized Smart Touch Surround Flow (STSF) catheter, with 56 holes around the electrode, lowers electrode-tissue temperature and thrombus risk. Thus, we conducted this prospective, randomized study to investigate if the HPSD strategy with STSF catheter in AF ablation procedures reduces the silent cerebral embolism (SCE) risk compared to the conventional approach with the Smart Touch (ST) catheter. METHODS: From June 2020 to September 2021, 100 AF patients were randomized 1:1 to the HPSD group using the STSF catheter (power set at 50 W) or the conventional group using the ST catheter (power set at 30 to 35 W). Pulmonary vein isolation was performed in all patients, with additional lesions at operator's discretion. High-resolution cerebral diffusion-weighted magnetic resonance imaging (hDWI) with slice thickness of 1 mm was performed before and 24-72 h after ablation. The incidence of new periprocedural SCE was defined as the primary outcome. Cognitive performance was assessed using the Montreal Cognitive Assessment (MoCA) test. RESULTS: All enrolled AF patients (median age 63, 60% male, 59% paroxysmal AF) underwent successful ablation. Post-procedural hDWI identified 106 lesions in 42 enrolled patients (42%), with 55 lesions in 22 patients (44%) in the HPSD group and 51 lesions in 20 patients (40%) in the conventional group (p = 0.685). No significant differences were observed between two groups regarding the average number of lesions (p = 0.751), maximum lesion diameter (p = 0.405), and total lesion volume per patient (p = 0.669). Persistent AF and CHA2DS2-VASc score were identified as SCE determinants during AF ablation procedure by multivariable regression analysis. No significant differences in MoCA scores were observed between patients with SCE and those without, both immediately post-procedure (p = 0.572) and at the 3-month follow-up (p = 0.743). CONCLUSIONS: Involving a small sample size of 100 AF patients, this study reveals a similar incidence of SCE in AF ablation procedures, comparing the HPSD strategy using the STSF catheter to the conventional approach with the ST catheter. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04408716. AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

Renal nerve stimulation identifies renal innervation and optimizes the strategy for renal denervation in canine.

BACKGROUND: Renal denervation (RDN) was still performed without any intra-procedural method for nerve mapping. Whether renal nerve stimulation (RNS) is an efficient way to identify renal autonomic innervation and optimize the strategy for RDN remain to be worthy for further exploration. METHODS: The characteristics of renal autonomic innervation at the sites with different blood pressure (BP) responses to RNS were explored. Then, dogs anatomically eligible for RDN were randomly assigned into elevated BP response ablation group, reduced BP response ablation group, and RNS-control group. The postoperative outcomes were measured at baseline and after 4 weeks follow-up. RESULTS: The proportion of afferent sensory nerve was higher at elevated BP response sites (ERS) than reduced BP response sites (RRS) and non-response sites (NRS) (P = 0.012 and P = 0.004). Conversely, the proportion of parasympathetic nerve at RRS was the highest (RRS vs. ERS, P = 0.017; RRS vs. NRS, P = 0.023). More importantly, there was a significant correlation between systolic blood pressure changes and the area ratios of afferent sensory and parasympathetic nerve (R = 0.859; P < 0.001). In addition, ablation at BP-elevation sites can result in a significant decrease in BP and plasma norepinephrine (NE) after 4 weeks (P = 0.002; P = 0.008), while ablation at BP-reduction sites can lead to significant increases in BP and plasma NE (P = 0.016; P = 0.033). CONCLUSIONS: RNS is an effective method to identify renal autonomic innervation. It could not only help to identify optimal target sites, but also avoid ablation of sympathetic-inhibitory areas during RDN.

Effects of different ablation settings on lesion dimensions in an ex vivo swine heart model: Baseline impedance, irrigant, and electrode configuration.

INTRODUCTION: Intramural or epicardial locations of the arrhythmogenic substrate are regarded as one of the main reasons for radiofrequency (RF) catheter ablation failure. This study aims to conduct a comprehensive analysis of various factors including baseline impedance, irrigant and electrode configuration at similar ablation index (AI) value. METHODS: In 12 ex vivo swine hearts, RF ablation was performed at a target AI value of 500 and a multistep impedance load (100-180 Ω) in 4 settings: (1) conventional unipolar configuration with an irrigant of normal saline (NS); (2) conventional unipolar configuration with an irrigant of half normal saline (HNS); (3) bipolar configuration with an irrigant of NS; (4) sequential unipolar configuration with an irrigant of NS. The relationships between lesion dimensions and above factors were examined. RESULTS: Baseline impedance had a strong negative linear correlation with lesion dimensions at a certain AI. The correlation coefficient between baseline impedance and depth, width, and volume were R = -0.890, R = -0.755 and R = -0.813, respectively (p < .01). There were 10 (total: 10/100, 10%; bipolar: 10/25, 40%) transmural lesions during the whole procedure. Bipolar ablation resulted in significantly deeper lesion than other electrode configurations. Other comparisons in our experiment did not achieve statistical significance. CONCLUSION: There is a strong negative linear correlation between baseline impedance and lesion dimensions at a certain AI value. Baseline impedance has an influence on the overall lesion dimensions among irrigated fluid and ablation configurations. Over a threshold impedance of 150 Ω, the predictive accuracy of AI can be compromised.

Left atrial appendage closure for stroke prevention in atrial fibrillation patients: A promise that came true.

Anticoagulation therapy plays a crucial role in the management of atrial fibrillation (AF), considering the high morbidity and mortality of AF-related ischemic strokes. With the plausible hypothesis that left atrial appendage is the main source of thrombus in AF patients, left atrial appendage closure (LAAC) has been regarded as a potential substitute to oral anticoagulation in order to meet the unmet needs for stroke prevention, particularly in patients with high bleeding risk. Notable advancements in safety, efficacy, and device innovation have been made in recent years, albeit concerns still remain regarding the insufficient efficacy data, device-related complications, and the need for procedural optimization. We aim to review current knowledge about LAAC and provide potential future directions for the remaining key issues.

Emergency catheter ablation: A feasible option for acute treatments of patients with unstable pre-excited atrial fibrillation.

BACKGROUND: Pre-excited atrial fibrillation (AF) is associated with increased risk of life-threatening events. However, at times, patients with pre-excited AF still repetitively suffer from hemodynamic disturbance, with resistance to acute treatments of antiarrhythmic therapy and cardioversion. METHODS: To evaluate the feasibility in correcting hemodynamic disturbance, patients with pre-excited AF who underwent catheter ablation of accessory pathway as an emergency procedure, were retrospectively collected from two centers of China. The medical records of patients were analyzed and summarized in this case series. RESULTS: Five patients with pre-excited AF who received emergency catheter ablation of accessory pathway, were collected from two contributor centers and reported in this case series. All collected patients still repetitively suffered from hemodynamic disturbance induced by rapid anterograde conduction of AF via pathway, even guideline recommended acute interventions of intravenous antiarrhythmic therapy and cardioversion had been performed. Finally, as an emergency procedure, catheter ablation of accessory pathway was performed in collected patients. Correspondingly, the hemodynamic unstable status was greatly relieved. Meanwhile, all collected patients with high risk of pre-excited AF were combined with left-sided accessory pathway, with shortest RR interval of widened pre-excited QRS complex less than 250 ms. Thus, combination with left-sided pathway is proposed as an indicator for the increased risk of life-threatening events in patients with high risk of pre-excited AF. CONCLUSIONS: Emergency catheter ablation of accessory pathway is an effective option for the acute managements of patients with high risk of pre-excited AF in unstable hemodynamics, which is resistant to antiarrhythmic therapy and cardioversion.

A nomogram based on CHADS2 score for predicting atrial fibrillation recurrence after cryoballoon ablation.

BACKGROUND: As reported, CHADS2 scoring system moderately predicts the atrial fibrillation (AF) recurrence, a common event after cryoballoon ablation. We aimed to improve the diagnostic accuracy of the CHADS2 score by adding several routine auxiliary detection indicators into the scoring system and constructing a CHADS2 score-based nomogram to predict AF recurrence in patients with paroxysmal AF undergoing cryoballoon ablation. METHODS: Eighty-four patients with paroxysmal AF undergoing cryoballoon ablation were enrolled. Baseline characteristics were collected. The multivariable Cox proportional hazards model was used to identify the significantly related predictors of recurrence and to construct the nomogram whose performance was evaluated by the discrimination and calibration tests. RESULTS: Thirty-five patients developed AF recurrence after a mean follow up of 19.0 ± 15.77 months. In the Cox multivariate model, CHADS2 (>2) (hazard ratio [HR]: 2.38; 95% confidence interval [CI]: 1.14-4.98, p = .021) and albumin-to-globulin ratio (AGR) (HR: 2.49; 95% CI: 1.26-4.92, p < .008) were independent risk factors associated with AF recurrence. In addition to CHADS2 , AGR and red blood cell distribution width were used to construct the nomogram. As a result, the discrimination of the concordance index for the predictive model of AF recurrence was increased from 0.56 (95% CI: 0.494-0.632) to 0.712 (95% CI: 0.631-0.811). The 24-month one well matched the ideal 45° line among the calibration plots for 6, 12, and 24 months' recurrence-free survival. CONCLUSION: This novel easy-to-use CHADS2 score-based nomogram may be used to predict AF recurrence for patient of paroxysmal AF undergoing cryoballoon ablation. Further external validation is still needed.

Prednisone Ameliorates Atrial Inflammation and Fibrosis in Atrial Tachypacing Dogs.

Atrial inflammation and fibrosis have long been considered culprits in the development of atrial fibrillation (AF). Prior clinical studies showed that corticosteroid therapy is beneficial in patients with AF. Here we sought to determine whether prednisone treatment prevents atrial tachypacing (ATP) induced atrial fibrosis.Dogs were randomized into the sham, ATP, ATP + low-dose prednisone (ALP), and ATP + high-dose prednisone (AHP) groups. After 6 days of recovery from surgery, dogs were subjected to ATP at 400 beats per minute for 4 weeks while being treated with prednisone (15 or 40 mg/day) or a placebo. Pacemakers were not activated in the sham group.Compared with the ATP group, the expression of collagen I, collagen III, α-smooth muscle actin, transforming growth factor-ß1 and connective tissue growth factor were significantly reduced in the ALP and AHP groups. Fluorescence assays showed that reactive oxygen species formation in the right atrium was suppressed in the ALP and AHP groups compared with the ATP group. The protein level of NADPH oxidase 2 was reduced in the ALP and AHP groups' versus ATP group, while NOX4 and NOX5 were unchanged. ATP-induced downregulation of BH4 and eNOS uncoupling in the atria was partially restored in the prednisone-treated groups.Our study demonstrated that atrial fibrosis induced by ATP were suppressed by prednisone. Low-dose prednisone was also effective in suppressing the development of atrial fibrosis.

microRNA-454-mediated NEDD4-2/TrkA/cAMP axis in heart failure: Mechanisms and cardioprotective implications.

The current study aimed to investigate the mechanism by which miR-454 influences the progression of heart failure (HF) in relation to the neural precursor cell expressed, developmentally downregulated 4-2 (NEDD4-2)/tropomyosin receptor kinase A (TrkA)/cyclic adenosine 3',5'-monophosphate (cAMP) axis. Sprague-Dawley rats were used to establish a HF animal model via ligation of the left anterior descending branch of the coronary artery. The cardiomyocyte H9c2 cells were treated with H2 O2 to stimulate oxidative stress injury in vitro. RT-qPCR and Western blot assay were subsequently performed to determine the expression patterns of miR-454, NEDD4-2, TrkA, apoptosis-related proteins and cAMP pathway markers. Dual-luciferase reporter gene assay coupled with co-immunoprecipitation was performed to elucidate the relationship between miR-454, NEDD4-2 and TrkA. Gain- or loss-of-function experiments as well as rescue experiments were conducted via transient transfection (in vitro) and adenovirus infection (in vivo) to examine their respective functions on H9c2 cell apoptosis and myocardial damage. Our results suggested that miR-454 was aberrantly downregulated in the context of HF, while evidence was obtained suggesting that it targeted NEDD4-2 to downregulate NEDD4-2 in cardiomyocytes. miR-454 exerted anti-apoptotic and protective effects on cardiomyocytes through inhibition of NEDD4-2, while NEDD4-2 stimulated ubiquitination and degradation of TrkA protein. Furthermore, miR-454 activated the cAMP pathway via the NEDD4-2/TrkA axis, which ultimately suppressed cardiomyocyte apoptosis and attenuated myocardial damage. Taken together, the key findings of the current study highlight the cardioprotective role of miR-454, which is achieved through activation of the cAMP pathway by impairing NEDD4-2-induced TrkA ubiquitination.

Catheter ablation vs. antiarrhythmic drugs as 'first-line' initial therapy for atrial fibrillation: a pooled analysis of randomized data.

AIMS: Catheter ablation (CA) is recommended for patients with atrial fibrillation (AF) after failure of antiarrhythmic drugs (AADs). The role of CA as 'initial therapy' for AF is to be determined. METHODS AND RESULTS: Following PRISMA guideline an up-to-date pooled analysis of randomized data comparing ablation vs. AADs as first-line therapy for symptomatic AF was performed. The primary outcome was recurrence of atrial tachyarrhythmia. The secondary outcomes were improvement in quality-of-life (QoL) and major adverse events. A total of 997 patients from five randomized trials were enrolled (mean age 57.4 years, 68.6% male patients, 98% paroxysmal AF, mean follow-up 1.4 years). The baseline characteristics were similar between the ablation and AADs group. Overall pooled analysis showed that, as compared with AADs, CA as first-line therapy was associated with significantly higher freedom from arrhythmia recurrence (69% vs. 48%, odds ratio: 0.36, 95% confidence interval: 0.27-0.48, P < 0.001). This significance was maintained in subgroup analyses of 1- and 2-year follow-up (P < 0.001). Catheter ablation was associated with significantly greater improvement in QoL regarding AFEQT score and 36-Item Short-Form Health Survey score. The incidence of serious adverse events between ablation and AADs group (5.6% vs. 4.9%, P = 0.62) was similar. CONCLUSIONS: Catheter ablation as 'initial therapy' was superior to AADs in maintenance of sinus rhythm and improving QoL for patients with symptomatic paroxysmal AF, without increasing risk of serious adverse events.

Rhythm control for patients with atrial fibrillation complicated with heart failure in the contemporary era of catheter ablation: a stratified pooled analysis of randomized data.

AIMS: The optimal treatment for patients with atrial fibrillation (AF) and heart failure (HF) has been a subject of debate for years. We aimed to evaluate the efficacy and safety of rhythm control strategy in patients with AF complicated with HF regarding hard clinical endpoints. METHODS AND RESULTS: Up-to-date randomized data comparing rhythm control using antiarrhythmic drugs (AADs) vs. rate control (Subset A) or rhythm control using catheter ablation vs. medical therapy (Subset B) in AF and HF patients were pooled. The primary outcomes were all-cause mortality, re-hospitalization, stroke, and thromboembolic events. A total of 11 studies involving 3598 patients were enrolled (Subset A: 2486; Subset B: 1112). As compared with medical rate control, the AADs rhythm control was associated with similar all-cause mortality [odds ratio (OR): 0.96, P = 0.65], significantly higher rate of re-hospitalization (OR: 1.25, P = 0.01), and similar rate of stroke and thromboembolic events (OR: 0.91, P = 0.76,); however, as compared with medical therapy, catheter ablation rhythm control was associated with significantly lower all-cause mortality (OR: 0.51, P = 0.0003), reduced re-hospitalization rate (OR: 0.44, P = 0.003), similar rate of stroke events (OR: 0.59, P = 0.27), greater improvement in left ventricular ejection fraction [weighted mean difference (WMD): 6.8%, P = 0.0004], lower arrhythmia recurrence (29.6% vs. 80.1%, OR: 0.04, P < 0.00001), and greater improvement in quality of life (Minnesota Living with Heart Failure Questionnaire score) (WMD: -9.1, P = 0.007). CONCLUSION: Catheter ablation as rhythm control strategy substantially improves survival rate, reduces re-hospitalization, increases the maintenance rate of sinus rhythm, contributes to preserve cardiac function, and improves quality of life for AF patients complicated with HF.

Laser-Ablation-Produced Cobalt Nickel Phosphate with High-Valence Nickel Ions as an Active Catalyst for the Oxygen Evolution Reaction.

Cost-effective, highly efficient and stable non-noble metal-based catalysts for the oxygen evolution reaction (OER) are very crucial for energy storage and conversion. Here, an amorphous cobalt nickel phosphate (CoNiPO4 ), containing a considerable amount of high-valence Ni3+ species as an efficient electrocatalyst for OER in alkaline solution, is reported. The catalyst was converted from Co-doped Ni2 P through pulsed laser ablation in liquid (PLAL) and exhibits a large specific surface area of 162.5 m2 g-1 and a low overpotential of 238 mV at 10 mA cm-2 with a Tafel slope of 46 mV dec-1 , which is much lower than those of commercial RuO2 and IrO2 . This work demonstrates that PLAL is a powerful technology for generating amorphous CoNiPO4 with high-valence Ni3+ , thus paving a new way towards highly effective OER catalysts.

The GPR55 antagonist CID16020046 protects against ox-LDL-induced inflammation in human aortic endothelial cells (HAECs).

Atherosclerosis is a commonplace cardiovascular disease which affects most people in old age. While its causes are currently poorly understood, continuous study is being performed in order to elucidate both the pathogenesis and treatment of this insidious disease. Atherosclerosis is presently thought to be linked to several factors such as endothelial dysfunction, monocyte adhesion to the intima of the artery, and increased oxidative stress. Oxidized low-density lipoprotein (ox-LDL), colloquially known as the "bad cholesterol", is known to play a critical role in the previously mentioned atherosclerotic processes. In this study, our goal was to elucidate the role of the lysophospholipid receptor G protein-coupled receptor 55 (GPR55) and its antagonist, the cannabinoid CID16020046, in endothelial dysfunction. While their existence and especially their role in atherosclerosis has only semi-recently been elucidated, a growing body of research has begun to link their interaction to antiatherosclerosis. In our research, we found CID16020046 to have distinct atheroprotective properties such as anti-inflammation, antioxidant, and inhibition of monocyte attachment to endothelial cells. While there was previously a small body of research regarding the potential of cannabinoids to treat or prevent atherosclerosis, studies on the treatment potential of CID16020046 were even fewer. Thus, this study is one of the first to explore the effects of cannabinoids in atherosclerosis. Our findings in the present study provide a strong argument for the use of CID16020046 in the treatment of atherosclerosis as well as a basis for further experimentation using cannabinoids as therapy against atherosclerosis.

Unique mechanistic insights into the beneficial effects of angiotensin-(1-7) on the prevention of cardiac fibrosis: A metabolomic analysis of primary cardiac fibroblasts.

BACKGROUND: Cell metabolic pathways are highly conserved among species and change rapidly in response to drug stimulation. Therefore, we explore the effects of angiotensin-(1-7) in a primary cell model of cardiac fibrosis established in angiotensin II-stimulated cardiac fibroblasts via metabolomics analysis and further clarify the potential protective mechanism of angiotensin-(1-7). METHODS AND RESULTS: After exposing cardiac fibroblasts to angiotensin II and/or angiotensin-(1-7), 172 metabolites in these cells were quantified and identified by gas chromatography-mass spectrometry. The data were subsequently analyzed by orthogonal partial least squares discriminant analysis to shortlist biochemically significant metabolites associated with the antifibrotic action of angiotensin-(1-7). Seven significant metabolites were identified: 10,13-dimethyltetradecanoic acid, arachidonic acid, aspartic acid, docosahexaenoic acid (DHA), glutathione, palmitelaidic acid, and pyroglutamic acid. By metabolic network analysis, we found that these metabolites were involved in six metabolic pathways, including arachidonic acid metabolism, leukotriene metabolism, and the γ-glutamyl cycle. Since these metabolic pathways are related to calcium balance and oxidative stress, we further verified that angiotensin-(1-7) suppressed the abnormal extracellular calcium influx and excessive accumulation of intracellular reactive oxygen species (ROS) in angiotensin II-stimulated cardiac fibroblasts. Furthermore, we found that angiotensin-(1-7) suppressed the abnormal calcium- and ROS-dependent activation of calcium/calmodulin-dependent protein kinase II delta (CaMKIIδ), the increased expression of CaMKIIδ-related proteins (NADPH oxidase 4 (Nox4), cellular communication network factor 2 (CTGF), and p-ERK1/2), and excessive collagen deposition in vitro and in vivo. CONCLUSIONS: Angiotensin-(1-7) can ameliorate the angiotensin II-stimulated metabolic perturbations associated with cardiac fibroblast activation. These metabolic changes indicate that modulation of calcium- and ROS-dependent activation of CaMKIIδ mediates the activity of angiotensin-(1-7) against cardiac fibrosis. Moreover, pyroglutamic acid and arachidonic acid may be potential biomarkers for monitoring the antifibrotic action of angiotensin-(1-7).

Synergy of pulmonary vein isolation and catheter renal denervation in atrial fibrillation complicated with uncontrolled hypertension: Mapping the renal sympathetic nerve and pulmonary vein (the pulmonary vein isolation plus renal denervation strategy)?

INTRODUCTION: Disturbance of sympathetic and vagal nervous system participates in the pathogenesis of hypertension and atrial fibrillation (AF). Renal denervation (RDN) can modulate autonomic nervous activity and reduce blood pressure (BP) in hypertensive patients. We aimed to evaluate the effect of RDN combined with pulmonary vein isolation (PVI) in patients with AF and hypertension. METHODS: Clinical trials including randomized data comparing PVI plus RDN vs PVI alone were enrolled. Primary outcome was incidence of AF recurrence after procedure. RESULTS: A total of 387 patients, of them 252 were randomized and were enrolled. Mean age was 57 ± 10 years, 71% were male, and mean left ventricular ejection fraction was 57.4% ± 6.9%. Follow-up for randomized data was 12 months. Overall comparison for primary outcome showed that PVI + RDN was associated with significantly lower AF recurrence as compared with PVI alone (35.8% vs 55.4%, P < 0.0001). This advantageous effect was consistently maintained among randomized patients (37.3% vs 61.9%, odds ratio = 0.37, P = 0.0001), and among patients with implanted devices for detection of AF recurrence (38.9% vs 61.6%, P = 0.007). Post-hoc sensitivity and regression analysis demonstrated very good stability of this primary result. Pooled Kaplan-Meier analysis further showed that PVI + RDN was associated with significantly higher freedom from AF recurrence as compared with PVI alone (log-rank test, P = 0.001). Besides, RDN resulted in significant BP reduction without additionally increasing the risk of adverse events. CONCLUSIONS: RDN may provide synergetic effects with PVI to reduce the burden of AF and improve BP control in patients with AF and uncontrolled hypertension.

Selective vs. Global Renal Denervation: a Case for Less Is More.

PURPOSE OF REVIEW: Review the renal nerve anatomy and physiology basics and explore the concept of global vs. selective renal denervation (RDN) to uncover some of the fundamental limitations of non-targeted renal nerve ablation and the potential superiority of selective RDN. RECENT FINDINGS: Recent trials testing the efficacy of RDN showed mixed results. Initial investigations targeted global RDN as a therapeutic goal. The repeat observation of heterogeneous response to RDN including non-responders with lack of a BP reduction, or even more unsettling, BP elevations after RDN has raised concern for the detrimental effects of unselective global RDN. Subsequent studies have suggested the presence of a heterogeneous fiber population and the potential utility of renal nerve stimulation to identify sympatho-stimulatory fibers or "hot spots." The recognition that RDN can produce heterogeneous afferent sympathetic effects both change therapeutic goals and revitalize the potential of therapeutic RDN to provide significant clinical benefits. Renal nerve stimulation has emerged as potential tool to identify sympatho-stimulatory fibers, avoid sympatho-inhibitory fibers, and thus guide selective RDN.

Angiotensin II upregulates fibroblast-myofibroblast transition through Cx43-dependent CaMKII and TGF-ß1 signaling in neonatal rat cardiac fibroblasts.

In cardiac fibroblasts, angiotensin II (Ang II) can increase connexin 43 (Cx43) expression and promote calmodulin-dependent protein kinase II (CaMKII) activation. Cx43 overexpression is crucial for the fibroblast-myofibroblast transition. The main purpose of the present study was to investigate the role of CaMKII in regulating Cx43 expression and to determine whether the CaMKII/Cx43 pathway is essential for controlling fibroblast activation and differentiation. In vivo, 4 weeks of Ang II infusion enhanced CaMKII activation but reduced Cx43 expression in hearts undergoing fibrosis remodeling, while in cultured neonatal rat fibroblasts, CaMKII activation upregulated Cx43 expression via transforming growth factor-beta1 (TGF-ß1). CaMKII inhibition by Ang-(1-7) or autocamtide 2-related inhibitory peptide reversed the Ang II-induced changes in Cx43 expression and attenuated Ang II-induced upregulation of alpha smooth muscle actin and TGF-ß1 in both Ang II-infused rats and cultured fibroblasts. Based on the in vivo and in vitro experimental results, CaMKII plays a pivotal role in the Ang II-mediated fibroblast-myofibroblast transition by modulating the expressions of TGF-ß1 and Cx43. We conclude that Ang II mediates the fibroblast-myofibroblast transition partially via the Ang II/CaMKII/TGF-ß1/Cx43 signaling pathway.

The Role of Oxygen Therapy in Normoxemic Acute Coronary Syndrome: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: Supplemental oxygen has been commonly used in the cases of acute coronary syndrome (ACS); however, recent evidence suggests that high-concentration oxygen supplementation and hyperbaric oxygen in ACS patients are associated with adverse cardiovascular effects. OBJECTIVE: The purpose of this article is to systematically review the role of supplemental oxygen therapy in normoxemic patients with ACS. METHODS: A search for randomized controlled trials before November 2017 in biomedical databases was performed, and a total of 6 eligible studies with 7508 participants were identified. Four studies reported all-cause mortality after randomization, whereas 3 studies measured myocardial infarct size using cardiac enzyme levels and magnetic resonance imaging. The effect size of our primary end point was the odds ratio for all-cause mortality. The mean difference was calculated as a secondary outcome for myocardial infarct size. RESULTS: Compared with ambient air or titrated oxygen, high-concentration oxygen therapy did not significantly decrease all-cause mortality (odds ratio, 1.01; 95% confidence interval [CI], 0.81-1.25; P = .95) within 1 year nor infarct size detected by peak cardiac troponin (mean difference, -0.53 ng/mL; 95% CI, -1.20 to 0.14; P = .12) and magnetic resonance imaging (mean difference, 1.45 g; 95% CI, -1.82 to 4.73; P = .39). These outcomes were listed through a fixed-effects model because of low statistical heterogeneity across the studies. CONCLUSIONS: Oxygen therapy did not significantly reduce clinical all-cause mortality and myocardial infarct size in ACS patients with normoxemia. Further large-scale randomized clinical trials are warranted to evaluate the cardiovascular effects in this field.

Preliminary effects of renal denervation with saline irrigated catheter on cardiac systolic function in patients with heart failure: A Prospective, Randomized, Controlled, Pilot Study.

OBJECTIVE: To assess efficacy and safety of renal denervation (RDN) for heart failure (HF). BACKGROUND: RDN has been demonstrated to be an effective method in lowing overactive sympathetic nerve. However, it's feasibility and efficacy for HF is unclear. METHODS: In this randomized, controlled pilot study, patients with HF were randomly assigned in 1:1 ratio to undergo RDN plus optimal medical therapy (RDN group) or only optimal medical therapy (control group). Before randomization, patients received optimal medical therapy at least half a year. Primary efficacy end point was the change in LVEF over six months; secondary efficacy end points were the change in six-minute walk distance and SF-36 Health Survey scores over six months. RESULTS: Up to Apr 2015, sixty symptomatic HF patients were successfully enrolled into study. Thirty patients were randomly assigned to RDN group and 30 patients were randomly assigned to control group. All patients completed six months follow up. During follow up, no severe adverse events were observed. Blood pressure was stable in both groups. Patients in RDN group had shown a significant improvement in LVEF (P < 0.001), SMWD (P = 0.043), NYHA class (P < 0.001), NT-proBNP (P < 0.001) and office heart rate (P = 0.008). Compared with control group, RDN patients were associated with significant improvement in all domains of SF-36 but bodily pain (P = 0.74). No significant change in estimate glomerular filtration nor complication of renal artery stenosis were observed. CONCLUSIONS: Results imply that RDN could be safely applied to treatment of HF and probably improve cardiac systolic function and patients' quality of life. © 2016 Wiley Periodicals, Inc.

The effect of two different renal denervation strategies on blood pressure in resistant hypertension: Comparison of full-length versus proximal renal artery ablation.

BACKGROUND: Renal denervation (RDN) is used to manage blood pressure (BP) in patients with resistant hypertension (rHT), but effectiveness is still a concern, and key arterial portion for successful RDN is not clear. OBJECTIVE: The aim of this study was to investigate the efficacy and safety of proximal versus full-length renal artery ablation in patients with resistant hypertension (rHT). METHODS: Forty-seven patients with rHT were randomly assigned to receive full-length ablation (n = 23) or proximal ablation (n = 24) of the renal arteries. All lesions were treated with radiofrequency energy via a saline-irrigated catheter. Office BP was measured during 12 months of follow-up and ambulatory BP at baseline and 6 months (n = 15 in each group). RESULTS: Compared with full-length ablation, proximal ablation reduced the number of ablation points in both the right (6.1 ± 0.7 vs. 3.3 ± 0.6, P < 0.001) and the left renal arteries (6.2 ± 0.7 vs. 3.3 ± 0.8, P < 0.001), with significantly shorter RF delivery time (P < 0.001), but higher RF power (P = 0.011). Baseline office BPs was 179.4 ± 13.7/102.8 ± 9.4 mm Hg in the full-length group and 181.9 ± 12.8/103.5 ± 8.9 mm Hg in the proximal group (P > 0.5). Similar office BPs was reduced by -39.4 ± 11.5/-20.9 ± 7.1 mm Hg at 6 months and -38.2 ± 10.3/-21.5 ± 5.8 mm Hg at 12 months in the full-length group (P < 0.001), -42.0 ± 11.6/-21.4 ± 7.9 mm Hg at 6 months and -40.9 ± 10.3/-22.1 ± 5.6 mm Hg at 12 months in the proximal group (P < 0.001), and progressive BP reductions were observed over the 6 months (P < 0.001) in both groups. The drop in ambulatory 24-hr SBP and DBP were significantly less than the drop in office BP (P < 0.001). No renovascular or other adverse complications were observed. CONCLUSIONS: The results indicate that proximal RDN has a similar efficacy and safety profile compared with full-length RDN, and propose the proximal artery as the key portion for RDN. © 2016 Wiley Periodicals, Inc.