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.

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.

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.

Atrial overexpression of angiotensin-converting enzyme 2 improves the canine rapid atrial pacing-induced structural and electrical remodeling. Fan, ACE2 improves atrial substrate remodeling.

The purpose of this study was to investigate whether atrial overexpression of angiotensin-converting enzyme 2 (ACE2) by homogeneous transmural atrial gene transfer can reverse atrial remodeling and its mechanisms in a canine atrial-pacing model. Twenty-eight mongrel dogs were randomly divided into four groups: Sham-operated, AF-control, gene therapy with adenovirus-enhanced green fluorescent protein (Ad-EGFP) and gene therapy with Ad-ACE2 (Ad-ACE2) (n = 7 per subgroup). AF was induced in all dogs except the Sham-operated group by rapid atrial pacing at 450 beats/min for 2 weeks. Ad-EGFP and Ad-ACE2 group then received epicardial gene painting. Three weeks after gene transfer, all animals except the Sham group underwent rapid atrial pacing for another 3 weeks and then invasive electrophysiological, histological and molecular studies. The Ad-ACE2 group showed an increased ACE2 and Angiotensin-(1-7) expression, and decreased Angiotensin II expression in comparison with Ad-EGFP and AF-control group. ACE2 overexpression attenuated rapid atrial pacing-induced increase in activated extracellular signal-regulated kinases and mitogen-activated protein kinases (MAPKs) levels, and decrease in MAPK phosphatase 1(MKP-1) level, resulting in attenuation of atrial fibrosis collagen protein markers and transforming growth factor-ß1. Additionally, ACE2 overexpression also modulated the tachypacing-induced up-regulation of connexin 40, down-regulation of connexin 43 and Kv4.2, and significantly decreased the inducibility and duration of AF. ACE2 overexpression could shift the renin-angiotensin system balance towards the protective axis, attenuate cardiac fibrosis remodeling associated with up-regulation of MKP-1 and reduction of MAPKs activities, modulate tachypacing-induced ion channels and connexin remodeling, and subsequently reduce the inducibility and duration of AF.

[Prevalence and risk factors of atrial fibrillation in hospitalized patients with chronic kidney disease].

OBJECTIVE: Atrial fibrillation (AF) is the most common sustained tachyarrhythmia in the general population. AF and Chronic Kidney Disease (CKD) share several common risk factors. We investigated the association between chronic kidney disease and risk of atrial fibrillation in hospitalized patients with CKD. METHODS: One thousand one hundred and sixty-eight patients [(63.3 ± 14.2) years, 54.5% males] hospitalized CKD patients were included. AF was determined by electrocardiogram or medical history. The prevalence of atrial fibrillation was compared in CKD patients with various age, sex and glomerular filtration rate (eGFR). Binary logistic regression analysis was used to determine the risk factors of AF. RESULT: The mean eGFR was (22.2 ± 19.7) ml · min(-1) · 1.73 m(-2); eGFR was ≤ 45 ml · min(-1) · 1.73 m(-2) in 84.2% patients and 38.5% patients received hemodialysis. AF was present in 14.2% of the study population and 17.2% in patients ≥ 60 years old. Prevalence of AF was significantly higher in patients with eGFR ≤ 45 ml · min(-1) · 1.73 m(-2) compared patients with eGFR > 45 ml · min(-1) · 1.73 m(-2) (15.8% vs. 5.4%, P < 0.001). Binary logistic regression analysis showed that age, body mass index (BMI), heart failure (HF), left atrial diameter (LAD), eGFR and dialysis were independent risk factors for AF. CONCLUSIONS: AF is much more frequent in CKD patients than in the general population. Age, BMI, HF, LAD, eGFR and dialysis are risk factors for AF in hospitalized patients with CKD.

Current problems in renal denervation and a hope to break the stage.

Renal denervation (RDN) is currently confronted with the considerable heterogeneity of different post-procedural blood pressure responses. The challenges predominantly arise from not only the lack of selection of appropriate responders but also the absence of detection for the successful endpoints of intervention. In this paper, we summarize the significant characteristics of potentially appropriate hypertensive patients and propose a hopeful way to improve the accuracy of RDN, that is, the application of three-dimensional reconstruction technology combined with electrical renal nerve stimulation to guide the radiofrequency catheter ablation, which may promote the development of selective and accurate RDN in real-world clinical practice. This paper focuses on two current critical concerns of renal denervation (RDN): appropriate patient selection and the improvement in the accuracy of selective RDN. A hopeful way of accurate RDN may be the combination of 3D electroanatomic mapping systems for the renal artery with modified renal nerve stimulation (RNS) techniques and technology for appropriate hypertensive candidates.

The intrarenal blood pressure modulation system is differentially altered after renal denervation guided by different intensities of blood pressure responses.

The aim of this study was to investigate alterations in the intrarenal blood pressure (BP) regulation system after renal denervation (RDN) guided by renal nerve stimulation (RNS). Twenty-one dogs were randomized to receive RDN at strong (SRA group, n = 7) or weak (WRA group, n = 7) BP-elevation response sites identified by RNS or underwent RNS only (RNS-control, RSC, n = 7). After 4 weeks of follow-up, renal sympathetic components, the main components of renin-angiotensin system (RAS) and the major transporters involved in sodium and water reabsorption were assessed by immunohistochemical analysis. Compared with RSC treatment, RDN therapy significantly reduced renal norepinephrine and tyrosine hydroxylase levels, decreased the renin content and inhibited the onsite generation of angiotensinogen. Moreover, the expression of exciting axis components, including angiotensin-converting enzyme (ACE), angiotensin II and angiotensin II type-1 receptor, was downregulated, while protective axis components for the cardiovascular system, including ACE2 and Mas receptors, were upregulated in both WRA and SRA groups. Moreover, RDN reduced the abundance of aquaporin-1 and aquaporin-2 in kidneys. Although RDN had a minimal effect on overall NKCC2 expression, its activation (p-NKCC2) and directional enrichment in the apical membrane (mNKCC2) were dramatically blunted. All these changes were more obvious in the SRA group than WRA group. Selective RDN guided by RNS effectively reduced systemic BP by affecting the renal neurohormone system, as well as the sodium and water transporter system, and these effects at sites with a strong BP response were more superior.

Camrelizumab-Related Lethal Arrhythmias and Myasthenic Crisis in a Patient with Metastatic Thymoma.

Immune checkpoint inhibitors (ICIs) have emerged in recent years as promising treatment options for several malignant tumors. However, ICI therapy has also been associated with various immune-related adverse events (irAEs), especially for patients with preexisting autoimmune status, which sometimes can be life-threatening. A 68-year-old woman diagnosed with metastatic thymoma was treated with camrelizumab, a new ICI, as her antitumor protocol. Eleven days after the first dose of camrelizumab, the patient was admitted to our hospital with symptoms of dyspnea, fatigue, and poor appetite. Workups on admission indicated dramatically elevated transaminase, troponin I, creatine kinase, and a new-onset conduction abnormality on electrocardiography. After detailed evaluation, ICI-related myocarditis, myositis, and hepatitis were diagnosed, and therapies including intravenous methylprednisolone were administered. Coronary angiography was performed to exclude acute coronary syndrome due to dynamic electrocardiography changes on day 3. She lapsed into a coma with respiratory muscle failure on the next day, which was highly suspected of myasthenic crisis. Mechanical ventilation and higher dose of methylprednisolone plus intravenous immunoglobulin were applied immediately. However, the third atrioventricular block occurred within the same day, and an urgent temporary pacemaker was placed. More seriously, refractory ventricular tachycardia (VT) occurred subsequently, and even multiple antiarrhythmic drugs used in combination failed to alleviate the VT storm. On day 5 of hospitalization, she suffered from ventricular fibrillation and died of cardiac arrest. In clinical practice, close follow-up should be conducted after ICI treatment, especially for patients already with or at high risk for autoimmune disorders. A multidisciplinary team approach is of importance for better management of patients with multiple organ involvement.

Present Evidence of Determinants to Predict the Efficacy of Renal Denervation.

Sympathetic overactivation is one of the main contributors to development and progress of hypertension. Renal denervation (RDN) has been evidenced by series of clinical trials for its efficacy and safety to treat overactivated sympathetic nervous system induced diseases. However, the results were inconsistent and not all patients benefited from RDN. Appropriate patient selection and intraoperative factors to improve the efficacy of RDN need to be solved urgently. Over the decade, research studies on the correlations between indicators and the antihypertensive effects have been conducted and made a fairly well progress. Herein, we comprehensively reviewed the research studies on how to make RDN more predictable or improve the efficacy of RDN and summarized these potential indicators or devices which might be applied in clinical settings.

Tailored Target Ablation Index Guided Pulmonary Vein Isolation in Treating Paroxysmal Atrial Fibrillation: A Single Center Randomized Study in Asian Population (AI-Asian-I).

Objective: To evaluate the efficacy and safety of lower ablation indexes (AI) guided pulmonary vein isolation (PVI) in treating paroxysmal atrial fibrillation (AF). Methods: Ninety patients with paroxysmal AF scheduled for radiofrequency ablation were randomly divided into three groups. The AI targets for PVI were as follows: In group A/B/C, 550/500/450 for roof and anterior wall, and 400/350/300 for posterior/inferior wall. The first-pass PVI rate, ablation time, complications and recurrence of atrial tachyarrhythmia (ATa) were compared. Results: The mean age was 62.5 years (male: 63.0%), mean body mass index (BMI): 24.35 ± 3.66 kg/m2. The baseline characteristics were comparable. There was no significant difference in the first-pass PVI rate among the three groups (left-sided-PV: 66.7% vs. 80% vs. 73.3%, P = 0.51; right-sided-PV: 70% vs. 83.3% vs. 73.3%, P = 0.64), also with similar gap rate during the procedural waiting time. At 1-year follow-up there was no significant difference in the recurrence rate of ATa among the three groups (10% vs. 13.3% vs. 13.3%, P = 1.00). The ablation time in the Group C was significantly less than that in the other two groups (47.8 min. vs. 47.0 min. vs. 36.6 min, P < 0.001). Higher AI seemed to link a non-significant trend toward higher rate of pericardial effusion (group A + B vs. group C:6.7% vs. 0%, P = 0.30), although the rate of overall complications was not different among the three groups. Conclusion: This randomized study shows that, a relatively lower target AI guided ablation may be similarly effective to achieve PVI with significantly reduced ablation time and obtain similar clinical outcome in treating paroxysmal AF in Asian population. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT:04549714].

Ultrasound Radiomics Nomogram Integrating Three-Dimensional Features Based on Carotid Plaques to Evaluate Coronary Artery Disease.

This study aimed to explore the feasibility of ultrasound radiomics analysis before invasive coronary angiography (ICA) for evaluating the severity of coronary artery disease (CAD) quantified by the SYNTAX score (SS). This study included 105 carotid plaques from 105 patients (64 low-SS patients, 41 intermediate-high-SS patients). The clinical characteristics and three-dimensional ultrasound (3D-US) features before ICA were assessed. Ultrasound images of carotid plaques were used for radiomics analysis. Least absolute shrinkage and selection operator (LASSO) regression, which generated several nonzero coefficients, was used to select features that could predict intermediate-high SS. Based on those coefficients, the radiomics score (Rad-score) was calculated. The selected clinical characteristics, 3D-US features, and Rad-score were finally integrated into a radiomics nomogram. Among the clinical characteristics and 3D-US features, high-density lipoprotein (HDL), apolipoprotein B (Apo B), and plaque volume were identified as predictors for distinguishing between low SS and intermediate-high SS. During the radiomics process, 8 optimal radiomics features most capable of identifying intermediate-high SS were selected from 851 candidate radiomics features. The differences in Rad-score between the training and the validation set were significant (p = 0.016 and 0.006). The radiomics nomogram integrating HDL, Apo B, plaque volume, and Rad-score showed excellent results in the training set (AUC, 0.741 (95% confidence interval (CI): 0.646-0.835)) and validation set (AUC, 0.939 (95% CI: 0.860-1.000)), with good calibration (mean absolute errors of 0.028 and 0.059 in training and validation sets, respectively). Decision curve analysis showed that the radiomics nomogram could identify patients who could obtain the most benefit. We concluded that the radiomics nomogram based on carotid plaque ultrasound has favorable value for the noninvasive prediction of intermediate-high SS. This radiomics nomogram has potential value for the risk stratification of CAD before ICA and provides clinicians with a noninvasive diagnostic tool.

Effect of Sacubitril-Valsartan on Restoration and Maintenance of Sinus Rhythm in Patients With Persistent Atrial Fibrillation.

Background: Existing studies have shown that sacubitril-valsartan ameliorated atrial remodeling in atrial fibrillation (AF) and favored maintenance of sinus rhythm in patients with AF and heart failure. However, the effect of sacubitril-valsartan in patients with persistent AF is yet unknown. We aimed to evaluate the effect of sacubitril-valsartan on restoration and maintenance of sinus rhythm in patients with persistent AF who underwent electrical cardioversion (ECV). Method: Consecutive patients with persistent AF who underwent ECV between 1 January 2016 and 30 September 2020 were investigated in this retrospective cohort study. All eligible patients were categorized into sacubitril-valsartan users and sacubitril-valsartan non-users based on whether they received treatment with sacubitril-valsartan or not. The endpoint was ineffictive ECV, defined as the composite of failure to terminate AF or any recurrence of AF during 30 days follow-up. Results: A total of 76 patients were enrolled in this study, including 28 sacubitril-valsartan users and 48 non-users. Within a follow-up of 30 days after ECV, the endpoint had occurred in 7 (25%) of 28 sacubitril-valsartan users and 25 (52%) of 48 non-users. Significantly lower rate of ineffictive ECV in sacubitril-valsartan users compared with non-users was shown in Kaplan-Meier survival curves (P = 0.02; Log-rank test). Multivariate Cox regression analysis indicated that sacubitril-valsartan use (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.14-0.91), amiodarone use (HR, 0.32; 95% CI, 0.13-0.78), left atrial diameter ≤ 39 mm (HR, 0.21; 95% CI, 0.06-0.71) were independently associated with a decreased rate of ineffective electrical cardioversion.

Extracardiac Vagal Stimulation-Assisted Cardioneuroablation: Dynamically Evaluating the Impact of Sequential Ganglionated Plexus Ablation on Vagal Control of SAN and AVN in Patients with Sinoatrial Node Dysfunction.

Cardioneuroablation (CNA) is proposed as a promising therapy for patients with sinoatrial node dysfunction (SND) that is mediated by excessive vagal tone. However, a series of urgent questions about CNA remain unanswered. From December 2020 to March 2022, six patients with symptomatic SND who underwent CNA were summarized in this report. Sequential CNA targeting Ao-SVC GP, PMLGP, RAGP, and LSGP was performed in patients, guided by fractionated intracardiac electrograms and dynamically evaluated by extracardiac vagal stimulation (ECVS). The results showed that Ao-SVC GP ablation led to a significant increase in heart rate (HR) and the elimination of sinus arrest evoked by ECVS, while the vagal responses of atrial ventricular block were eliminated by the ablation of PMLGP and LSGP. Post-procedure HR increased up to 64-86% of the maximum HR of an atropine test at baseline. The median HR from Holter monitoring increased from 52.8 ± 2.1 bpm at baseline to 73.0 ± 10.4 bpm after the procedure (p = 0.012) and to 71.3 ± 10.1 bpm at the six-month follow-up (p = 0.011). Bradycardia-related symptoms disappeared in all patients at the six-month follow-up. This case series reveals the feasibility of using the ECVS-assisted sequential CNA technique and indicates the critical role of ECVS in dynamically evaluating the impact of sequential CNA on the vagal control of SAN and AVN.

Mapping Renal Innervations by Renal Nerve Stimulation and Characterizations of Blood Pressure Response Patterns.

Increased sympathetic nervous activity is one of main contributors to pathogenesis and progression of hypertension. Renal denervation (RDN) has been demonstrated as a potential therapy for treatment of hypertension; however, lack of indicators of intra-/post-procedure results in inconsistent clinical outcomes. Renal nerve stimulation (RNS), a simple and promising method, could evoke elevated blood pressure as an intraoperative indicator for RDN. But related researches on patterns of blood pressure responses to RNS are still incomplete. To investigate and categorize the phenotypes of blood pressure response to RNS and heart rate alteration before and after RNS, 24 Chinese Kunming dogs were used to perform RNS from bifurcation to ostium of renal arteries after angiography, and a total of 483 stimulated sites were complete. We identified five different patterns of blood pressure response to RNS in 483 stimulated sites, (1) continuous ascending and finally keeping steady above baseline (26.9%), (2) declining and then rising over baseline (11.8%), (3) declining and then rising but below baseline (14.5%), (4) fluctuating in the vicinity of baseline (39.5%), and (5) continuous declining and finally keeping steady below baseline (7.2%), and found no difference in RR intervals among five blood pressure responses before and after renal nerve stimulation. Renal nerve stimulation could elicit different patterns of blood pressure response, which could potentially assist in distinguishing sympathetic-excitatory sites and sympathetic-inhibitory sites from mixed nerve components, which might help to improve the efficacy of RDN.

Efficacy and Safety of Long-Term Oral Bosentan in Different Types of Pulmonary Arterial Hypertension: A Systematic Review and Meta-Analysis.

OBJECTIVE: This systematic review and meta-analysis was conducted to identify if long-term bosentan is an effective and safe treatment for pulmonary arterial hypertension (PAH) regardless of type, including idiopathic PAH (IPAH), and PAH associated with congenital heart disease (APAH-CHD), connective tissue disease (APAH-CTD), and human immunodeficiency virus (APAH-HIV). METHODS: All relevant observations were systematically searched by two independent investigators and obtained from three databases, including PubMed, EMBASE and the Cochrane Library, from the inception of each database to February 2020. Currently, long-term administration was defined as no less than 12 months. A random-effects or fixed-effects model was selected according to outcomes of the heterogeneity test for meta-analysis, where standardized mean difference (SMD) with 95% confidence intervals (CIs) was used for continuous outcomes, in addition to the estimated effect (ES; 95% CI) for the synthesized survival rate. Furthermore, subgroup analysis was applied to analyze the differences of efficacy and survivals in each type of PAH cohort. RESULTS: Fifteen studies including a total of 659 subjects undergoing oral bosentan administration for at least 12 months were pooled in this quantitative review. Meta-analysis and subgroup analysis indicated that significant clinical benefits existed, including an improved 6-min walk distance (6MWD) and functional class (FC), in patients with APAH-CHD (6MWD: SMD 0.72, 95% CI 0.52-0.93, p < 0.0001; functional benefits: 50.4%, 95% CI 43.7-57.1%), APAH-HIV (6MWD: SMD 0.83, 95% CI 0.36-1.30, p = 0.001; functional benefits: 80.4%), and IPAH (SMD 0.54, 95% CI 0.28-0.80, p < 0.0001; functional benefits: 61.4%, 95% CI 54.2-68.5%), but a non-significant change in APAH-CTD (6MWD: SMD 0.18, 95% CI - 0.60 to 0.95, p = 0.656; functional benefits: 27.5%). Furthermore, among the hemodynamic parameters, long-term bosentan led to a significant decrease in mean pulmonary artery pressure (SMD - 0.86, p < 0.0001) in APAH-CTD, and a decrease in pulmonary vascular resistance (SMD - 0.65, p < 0.0001) and elevated oxygen saturation (SMD 0.30, p = 0.006) in APAH-CHD. Importantly, in all pooled studies, the overall survival indicated 1-, 2-, and 3-year survival rates of 94.3%, 88.8%, and 81.7%, respectively, in all-cause PAH, and subgroup analysis demonstrated a relative decreasing trend in patients with HIV, from a 2-year survival of 89.8% to a 3-year survival of 66.1%. Adverse drug reactions were relatively mild. CONCLUSION: In this systematic review and meta-analysis, long-term administration of oral bosentan has been identified as a well-tolerated and effective agent in different types of PAH. In addition, we conclude that long-term oral bosentan should be considered for patients with CTD to achieve a satisfactory exercise capacity, and for those with APAH-HIV to improve survivals, where more attention on adverse events is required.

Characteristics of Ang-(1-7)/Mas-Mediated Amelioration of Joint Inflammation and Cardiac Complications in Mice With Collagen-Induced Arthritis.

Objectives: Rheumatoid arthritis (RA) is a disabling disease with a high incidence that is regularly accompanied by cardiovascular complications. Several studies have suggested that renin-angiotensin-aldosterone system (RAAS) is closely associated with RA. The aim of this study was to investigate the mechanisms underlying Angiotensin-(1-7) [Ang-(1-7)] and its Mas receptor agonist (AVE0991) on joint inflammation and cardiac complications in a collagen-induced arthritis (CIA) model. Methods: Collagen type II was injected into DBA/1 mice to construct an arthritis model. CIA mice were treated with Ang-(1-7) (2.0 mg/kg intraperitoneally) and AVE0991 (3.0 mg/kg intraperitoneally). The serum levels of inflammatory cytokines [tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1 ß, IL-6, and C-reactive protein (CRP)] were determined by ELISA. The mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-κB) signaling pathways in joint tissues and the transforming growth factor (TGF)-ß/Smad pathway and levels of α-Smooth muscle action (SMA) and ß-myosin heavy chain (MHC) protein expression in cardiac tissues were assessed by western blots. The levels of TGF-ß/Smad pathway, α-SMA, and ß-MHC RNA in cardiac tissues were analyzed by real time-PCR. The levels of receptor activator of nuclear factor kappa ligand (RANKL) and promoting matrix metalloproteinase (MMP)-3 expression in the ankle joints were detected by immunohistochemistry and real time-PCR. Results: Ang-(1-7) and AVE0991 reduced the levels of inflammatory cytokines and inhibited the MAPKs and NF-κB signaling pathways in ankle joint tissues, reduced RANKL and MMP3 expression, and ameliorated local joint inflammation and bone destruction compared with the control group. In addition, Ang-(1-7) and AVE0991 attenuated the TGF-ß/Smad signaling pathway, reduced the levels of α-SMA and ß-MHC expression, and diminished inflammatory cell infiltration into the myocardial interstitium and myocardial interstitial fibrosis in the hearts of CIA mice. Conclusions: Ang-(1-7) alleviated joint damage caused by inflammation likely through the attenuation of NF-κB and MAPK pathways and ameliorated inflammation-induced cardiac fibrosis and activation of the TGF-ß/Smad pathway. Moreover, Ang-(1-7) was likely mediated through the Mas receptor. This study provides theoretical evidence for exploring novel clinical therapeutic approaches for RA and its cardiac complications.

Renin-angiotensin system-related gene polymorphisms are associated with risk of atrial fibrillation.

BACKGROUND: Renin-angiotensin system (RAS) plays an important role in atrial fibrillation (AF). Recently, many publications have studied the associations between RAS-related gene polymorphisms and AF risk, with inconsistent results. To further evaluate these associations, we carried out a meta-analysis of all the published studies. METHODS: Electronic searches were used to identify published studies evaluating RAS-related gene polymorphisms and AF risk before April 2009. We extracted data sets and performed meta-analysis with standardized methods. RESULTS: A meta-analysis of 12 publications on association between angiotensin-converting enzyme (ACE insertion/deletion) and AF risk was performed. The pooled relative risk (RR) of allele D versus I was 1.19 (95% CI, 1.07-1.32, P < .01), pooled RR of DD and DI versus II was 1.31(95% CI, 1.09-1.58, P < .01) and 1.06 (95% CI, 0.97-1.16, P = .22) respectively. In subgroup analysis, a stronger association was found in hypertensive population, Western ethnic, lone AF, and patients aged > or = 65 years, with pooled RR of DD versus II was 1.74 (95% CI, 1.39-2.18, P < .01), 1.27 (95% CI, 1.01-1.59, P = .04), 1.53 (95% CI, 1.31-1.78, P < .01) and 1.38 (95% CI, 1.10-1.73, P < .01), respectively. CONCLUSION: The results suggested an association between ACE insertion/deletion and AF risk. More large-scale studies are warranted to document the conclusive evidence of the effects of the RAS genes on AF risk.

Coronary score adds prognostic information for patients with acute coronary syndrome.

BACKGROUND: The aim of the present study was to explore the association of 3 coronary scores with major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: The 958 consecutive patients with ACS were followed up until either MACE or 31(st) December 2008 occurred; 257 patients reached clinical endpoints. Cox regression analysis demonstrated that the Gensini score was associated with 90-day MACE (relative risk (RR) 1.021, P=0.004), 6-month MACE (RR 1.021, P<0.001), 1-year MACE (RR 1.017, P=0.002), and MACE during follow-up (RR 1.010, P=0.040). Leaman score was associated with 90-day MACE (RR 1.094, P=0.014), 6-month MACE (RR 1.098, P=0.002), and 1-year MACE (RR 1.074, P=0.009). The logistic regression analysis demonstrated that the Gensini score (odds ratio (OR) 1.037, P=0.001), Leaman score (OR 1.165, P=0.007) and American College of Cardiology/American Heart Association (ACC/AHA) score (OR 1.235, P=0.025) were all associated with cardiogenic death. CONCLUSIONS: The Gensini score provides more valuable prognostic information on cardiovascular risk than either the Leaman or ACC/AHA score in patients with ACS.