This study aimed at investigating whether Angiotensin-(1-7) [Ang-(1-7)] could alleviate cardiac fibrosis by modulating the expression of Rac1 and Rad GTPase and evaluating the specific mechanism in rat cardiac fibroblasts (CFs) and in canine atrial rapid pacing models. Fresh CFs were isolated from ventricles of 1 ~ 3 day-old Sprague-Dawley rats, and were randomly divided into control group, LPS group, Ang-(1-7) group and LPS+Ang-(1-7) group. CCK8 was used to detect cell proliferation. qRT-PCR was to detect the mRNA expression of ACE2. Mongrel dogs were randomized into four groups: Sham-operated (Sham), AF-Control, AF-EGFP and AF-ACE2 groups. Immunoperoxidase staining was used to test Rac1 and Gem expression. Collagen fibers in heart were stained a red color and extent of cardiac fibrosis was evaluated. Histopathology was to observe actin,α-smooth. Enzyme-Linked Immunosorbent Assay was to detect Ang II and Ang-(1-7) expression in canine atrial tissue. And western blot analysis was to detect the protein expression of iNOS, COX2, α-SMA, Rac1, ACE, and AT1R in cells and tissues. Cellular experiments showed LPS promoted proliferation of fibroblasts, which could be inhibited by Ang-(1-7) (p < 0.05). Compared with control group, LPS-induced CFs showed a significant increase in protein expression of iNOS, COX2, and α-SMA, which promoted cell proliferation. However, the application of Ang-(1-7) reversed these effects and suppressed the ACE/AT1R signaling pathway in LPS-induced CFs. In animal experiments, ACE2 over-expression would up-regulate atrial Ang-(1-7) and AT2R and reduce atrial angiotensin II (Ang II) and AT1R expressions (p < 0.05). In AF-ACE2 group, Rac1 was down-regulated and Rad GTPase was up-regulated, in comparison with AF-Control and AF-EGFP groups, associated with reductions of CTGF, fibrosis-related factors α-SMA and N-cadherin. ACE2 was found to alleviate cardiac fibrosis through the Ang(1-7)/Mas signaling pathway in animal experiments.

Background Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome with high morbidity and mortality. Empagliflozin, an SGLT2 (sodium–glucose cotransporter 2) inhibitor, reduces adverse events in patients with HFpEF regardless of glycemic control. However, the precise cardioprotective mechanisms of SGLT2 inhibitor in HFpEF remain underexplored. Methods and Results A “2‐hit” mouse model of HFpEF was developed via the high‐fat diet combined with Nω‐nitro‐L‐arginine methyl ester. Male C57BL/6N mice were assigned to either a control group (n=10) or an HFpEF group (n=20), with the latter receiving empagliflozin (10 mg/kg per day, n=10) or vehicle (n=10) for 8 weeks. Cardiac function, hypertrophy, and fibrosis were evaluated by physiological, biochemical, and histological measurements. Mechanistic analysis, including RNA sequencing, Western blotting, and immunohistochemistry, was conducted. In vitro, H9c2 cardiomyocytes were exposed to angiotensin II and palmitate, followed by empagliflozin treatment. In vivo, empagliflozin treatment improved body weight, blood pressure, glucose tolerance, and reduced cardiac hypertrophy, fibrosis, and diastolic dysfunction in HFpEF mice. Mechanistic analysis revealed that empagliflozin modulated the AMPK (AMP‐activated protein kinase)/mTORC1 (mammalian target of rapamycin complex 1)/autophagy signaling pathway. Specifically, empagliflozin restored the autophagy markers (Beclin1 and LC3‐II [microtubule‐associated protein 1 light chain 3]) and altered the phosphorylation of AMPK, mTOR, and p70S6K (ribosomal protein S6 kinase beta‐1). Inhibition of AMPK or autophagy nullified the antihypertrophic effect of empagliflozin, underscoring the dependence on the AMPK/mTORC1/autophagy pathway. Conclusions Empagliflozin effectively ameliorates cardiac remodeling and diastolic dysfunction in HFpEF by enhancing autophagy via the AMPK/mTORC1 pathway. These findings elucidate the direct cardioprotective mechanisms of empagliflozin and suggest potential therapeutic molecular targets for HFpEF.

Hypertension is a common condition in cardiovascular medicine, and can lead to atrial enlargement, atrial fibrosis, and even the development of atrial fibrillation. Renal denervation (RDN) causes reduction in blood pressure (BP), but its effects on hypertension-related atrial remodeling remain unclear. This study aimed to explore the effects of RDN at BP-elevation/reduction sites guided by renal nerve stimulation (RNS) on atrial neural and structural remodeling in a hypertensive canine model. The twenty-four Chinese Kunming dogs were divided into three groups: (1) the reduced BP response ablation group (RRA group, n = 8), (2) the renal stimulation control group (RSC group, n = 8), and (3) the elevated BP response ablation group (ERA group, n = 8), which were followed for 4 weeks. Our results showed that in terms of atrial neural remodeling, compared with the RSC group, the ERA group exhibited reduced tyrosine hydroxylase (TH) protein expression and a lower TH/ choline acetyltransferase (ChAT) ratio. In contrast, the RRA group showed lower ChAT and muscarinic acetylcholine receptor 2 (CM2) protein expression, and an elevated TH/ChAT ratio. Compared with the RSC group, the ERA group presented a smaller myocyte area, reduced collagen I protein expression, and lower myocardial interstitial collagen fiber content. In contrast, the RRA group presented a larger myocyte area, increased collagen I protein expression, and greater collagen fiber content. Overall, RDN at elevated BP response sites improved atrial neural and structural remodeling under hypertensive conditions, whereas RDN at reduced BP response sites exacerbated the imbalance between atrial sympathetic and parasympathetic nerve activity and worsened structural remodeling.

Previous studies have demonstrated that cardioversion of atrial fibrillation may alleviate atrial remodeling. We aimed to investigate whether left atrial (LA) tissue fibrosis assessed by LGE-MRI, may be reversed after conversion of persistent atrial fibrillation (PersAF) to sinus rhythm. Patients with PersAF underwent two LGE-MRI scans following cardioversion were prospectively recruited. LA fibrosis was categorized into core zone (IIR > 1.61) and border zone (0.97 Fifty-three patients were included. The area of the border [22.2 (11.8-37.0) vs. 18.1 (11.8-25.2) cm 2 , p = 0.037] and core zones [0.9±3.0 vs. 0.1±0.6 cm 2 , p = 0.010] decreased from baseline, along with reductions in LAV, increase of LA ejection fraction and strain. After multivariable adjustment, ΔLATEF was correlated with Δborder zone (r 2 =0.155, p = 0.015), baseline left ventricular mass and ΔLATEF was correlated with Δcore zone (r 2 =0.286, p <0.001). The cardiac reverse remodeling is not related with Δborder zone and Δcore zone. Atrial fibrosis improved concomitantly with LA shrinkage and enhanced LA function after PersAF to sinus rhythm. LA fibrotic reverse is an independent parameter compared with the traditional definition of cardiac reverse remodeling. The clinical implications warrant further investigation.

AIMS:Atrial fibrillation/atrial flutter (AF/AFL) remains a significant public health concern on a global scale, with metabolic risks playing an increasingly prominent role. This study aimed to investigate comprehensive epidemiological data and trends concerning the metabolic risks related-AF/AFL burden based on the data from the Global Burden of Disease study in 2019. METHODS AND RESULTS:The analysis of disease burden focused on numbers, age-standardized rates of deaths, disability-adjusted life years (DALYs), and estimated annual percentage change, while considering factors of age, sex, sociodemographic index (SDI), and locations. In 2019, there was a culmination of 137 179 deaths and 4 099 146 DALYs caused by metabolic risks related-AF/AFL worldwide, with an increase of 162.95% and 120.30%, respectively from 1990. High and high-middle SDI regions predominantly carried the burden of AF/AFL associated with metabolic risks, while a shift towards lower SDI regions had been occurring. Montenegro had the highest recorded death rate (7.6 per 100 000) and DALYs rate (146.3 per 100 000). An asymmetrically inverted V-shaped correlation was found between SDI and deaths/DALYs rates. Moreover, females and the elderly exhibited higher AF/AFL burdens, and young adults (over 40 years old) also experienced an annual increase. CONCLUSION:The global AF/AFL burden related to metabolic risks has significantly increased over the past three decades, with considerable spatiotemporal, gender-based, and age-related heterogeneity. These findings shed valuable light on the trends in the burden of metabolic risks related-AF/AFL and offered insights into corresponding strategies.

Background:Previous trials of renal denervation (RDN) have been designed to investigate reduction of blood pressure (BP) as the primary efficacy endpoint using non-selective RDN without intraoperatively verified RDN success. It is an unmet clinical need to map renal nerves, selectively denervate renal sympathetic nerves, provide readouts for the interventionalists and avoid futile RDN. We aimed to examine the safety and efficacy of renal nerve mapping/selective renal denervation (msRDN) in patients with uncontrolled hypertension (HTN) and determine whether antihypertensive drug burden is reduced while office systolic BP (OSBP) is controlled to target level (＜140 mmHg). Methods:We conducted a randomized, prospective, multicenter, single-blinded, sham-controlled trial. The study combined two efficacy endpoints at 6 months as primary outcomes: The control rate of patients with OSBP ＜140 mmHg (non-inferior outcome) and change in the composite index of antihypertensive drugs (Drug Index) in the treatment versus Sham group (superior outcome). This design avoids confounding from excess drug-taking in the Sham group. Antihypertensive drug burden was assessed by a composite index constructed as: Class N (number of classes of antihypertensive drugs) × (sum of doses). 15 hospitals in China participated in the study and 220 patients were enrolled in a 1:1 ratio (msRDN vs Sham). The key inclusion criteria included: age (18-65 years old), history of essential HTN (at least 6 months), heart rate (≥70 bpm), OSBP (≥150 mmHg and ≤180 mmHg), ambulatory BP monitoring (ABPM, 24-h SBP ≥130 mmHg or daytime SBP ≥135 mmHg or nighttime SBP ≥120 mmHg), renal artery stenosis (＜50%) and renal function (eGFR ＞45 mL/min/1.73 m2). The catheter with both stimulation and ablation functions was inserted in the distal renal main artery. The RDN site (hot spot) was selected if SBP increased (≥5 mmHg) by intra-renal artery (RA) electrical stimulation; an adequate RDN was confirmed by repeated electronic stimulation if no increase in BP otherwise, a 2nd ablation was performed at the same site. At sites where there was decreased SBP (≥5 mmHg, cold spot) or no BP response (neutral spot) to stimulation, no ablation was performed. The mapping, ablation and confirmation procedure was repeated until the entire renal main artery had been tested then either treated or avoided. After msRDN, patients had to follow a predefined, vigorous drug titration regimen in order to achieve target OSBP (＜140 mmHg). Drug adherence was monitored by liquid chromatography-tandem mass spectrometry analysis using urine. This study is registered with ClinicalTrials.gov (NCT02761811) and 5-year follow-up is ongoing. Findings:Between July 8, 2016 and February 23, 2022, 611 patients were consented, 220 patients were enrolled in the study who received standardized antihypertensive drug treatments (at least two drugs) for at least 28 days, presented OSBP ≥150 mmHg and ≤180 mmHg and met all inclusion and exclusion criteria. In left RA and right RA, mapped sites were 8.2 (3.0) and 8.0 (2.7), hot/ablated sites were 3.7 (1.4) and 4.0 (1.6), cold spots were 2.4 (2.6) and 2.0 (2.2), neutral spots were 2.0 (2.1) and 2.0 (2.1), respectively. Hot, cold and neutral spots was 48.0%, 27.5% and 24.4% of total mapped sites, respectively. At 6 M, the Control Rate of OSBP was comparable between msRDN and Sham group (95.4% vs 92.8%, p = 0.429), achieved non-inferiority margin -10% (2.69%; 95% CI -4.11%, 9.83%, p ＜ 0.001 for non-inferiority); the change in Drug Index was significantly lower in msRDN group compared to Sham group (4.37 (6.65) vs 7.61 (10.31), p = 0.010) and superior to Sham group (-3.25; 95% CI -5.56, -0.94, p = 0.003), indicating msRDN patients need significantly fewer drugs to control OSBP ＜140 mmHg. 24-hour ambulatory SBP decreased from 146.8 (13.9) mmHg by 10.8 (14.1) mmHg, and from 149.8 (12.8) mmHg by 10.0 (14.0) mmHg in msRDN and Sham groups, respectively (p < 0.001 from Baseline; p > 0.05 between groups). Safety profiles were comparable between msRDN and Sham groups, demonstrating the safety and efficacy of renal mapping/selective RDN to treat uncontrolled HTN. Interpretation:The msRDN therapy achieved the goals of reducing the drug burden of HTN patients and controlling OSBP <140 mmHg, with only approximately four targeted ablations per renal main artery, much lower than in previous trials. Funding:SyMap Medical (Suzhou), LTD, Suzhou, China.

BackgroundCardioneuroablation (CNA) is recognized as a promising therapeutic option for adults with severe symptomatic bradycardia caused by excessive vagal tone. However, no pediatric cases have been reported to date. Therefore, the aim of this study is to evaluate the feasibility and efficacy of CNA in children.MethodsA 12-year-old male patient was hospitalized with symptoms of fatigue, palpitations, and syncope for more than 2 months, and was definitively diagnosed with functional sinoatrial node dysfunction by using a 12-lead electrocardiogram, 24-h Holter monitoring, loading dose of atropine test (0.04 mg/kg), and treadmill exercise test. Simultaneously, whole-exome sequencing was performed on the child and his core family members. After completing the preoperative examination and signing the informed consent form, the child underwent CNA therapy.ResultsFirst, the electroanatomic structures of both atria were mapped out by using the Carto 3 system, according to the protocol of purely anatomy-guided and local fractionated intracardiac electrogram–guided CNA methods. Then, the local fractionated intracardiac electrograms of each cardiac ganglionated plexus (GP), including the GP between the aortic root and the medial wall of the superior vena cava, the GP between the posterior wall of the coronary sinus ostium and the left atrium, the GP between the anterior antrum of the right superior pulmonary vein and the superior vena cava, the GP in the superolateral area around the root of the left superior pulmonary vein, the GP around the root of the right inferior pulmonary vein, and the GP around the root of the left inferior pulmonary vein, were used as targets for ablation at a power of 30 W with an ablation index of 350–400. At a 6-month follow-up, the child's heart rhythm saw a complete restoration to sinus rhythm and clinical symptoms disappeared.ConclusionThe first application of CNA in a child with symptomatic sinus bradycardia was achieved with better clinical outcomes. CNA can be carried out cautiously in children under suitable indications.

Renal nerve stimulation (RNS) could localize the renal nerve innervation through rapid blood pressure (BP) changes for renal denervation (RDN). Recently, novel BP response patterns have been demonstrated in animals. The current study was to verify the presence of these patterns in humans and examine the feasibility of using them to guide selective RDN. Fourteen patients with mild resistant hypertension were included in this prospective analysis. RNS was performed before and after radiofrequency-based RDN. Invasive monitoring was used continuously to obtain beat-to-beat BP. Ambulatory BP (ABP) monitoring was measured at baseline, 5–7 days, and 6–12 months, respectively. Five types of BP responses were summarized during RNS before RDN, namely: (1) BP persistently elevated; (2) BP dropped and then elevated above the baseline; (3) BP dropped and then recovered, but not over the baseline; (4) BP fluctuated in the vicinity of the baseline; and (5) BP persistently dropped. Selective RDN was performed at the site with elevated BP. The 24-h ABP decreased from 141 ± 12/94 ± 9 mmHg at baseline to 130 ± 11/85 ± 8 mmHg at 5 – 7 days (P = 0.001 for systolic BP [SBP], P = 0.003 for diastolic BP [DBP]) and 127 ± 11/85 ± 8 mmHg at 6 – 12 months (P = 0.009 for SBP, P = 0.019 for DBP). The average heart rate fell from 77 ± 8 bpm to 71 ± 5 bpm (P = 0.01) and 72 ± 7 bpm (P = 0.043), respectively. Our study showed five types of BP responses elicited by RNS in humans. RDN guided by these BP responses was feasible and resulted in obvious BP reduction, and they may potentially provide precise guidance for RDN.

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 CHA 2 DS 2 -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. Graphical Abstract AF = Atrial fibrillation, DWI = Diffusion-weighted magnetic resonance imaging, HPSD = High-power short-duration, ST = Smart Touch, STSF = Smart Touch Surround Flow.

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.

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.

Purpose: To characterize the magnetic resonance imaging features of primary intrahepatic lymphoepithelioma-like cholangiocarcinoma (LELCC). Materials and Methods: Thirty-four patients with 38 histologically confirmed LELCCs were enrolled retrospectively from January 2014 to August 2022. We evaluated the clinical features, histologic findings, and imaging manifestations on dynamic enhanced MRI. Results: 74% (25/34) of the cases were associated with EBV infection. Moreover, patients infected with EBV exhibited a lower level of Ki-67 proliferation. The serum CA199 level was elevated in 10 patients. The median tumor diameter was 2.8 cm (range, 1.1–8.7 cm). Most tumors were well-defined with a smooth or lobulated margin and showed peripheral hyperintensity and central hypointensity on T2-weighted imaging (T2WI). T2 hyperintense foci were recognized in 8 patients. In the dynamic enhanced MRI, 21 tumors demonstrated Type A enhancement pattern (rim enhancement), 10 demonstrated Type B (rapid wash-in and wash-out), and seven demonstrated Type C (rapid wash-in without wash-out). Capsular enhancement in PVP or DP was found in 22 tumors. A few patients had satellite lesions, portal vein thrombosis, bile duct dilatation, and distal metastasis. Lymph node metastases were discovered pathologically in 11 patients. Conclusions: MRI findings of LELCC vary and are non-specific. While a majority of LELCCs exhibit typical features of intrahepatic cholangiocarcinoma (iCCA), unique findings like T2 hyperintense foci or capsular enhancement could suggest LELCC. EBV infection and elevated tumor markers can aid in differentiation. However, given the mimics of some cases of liver hypervascular lesions, histological examination remains essential for definitive diagnosis.

Renal nerve stimulation (RNS) could localize the renal nerve innervation through rapid blood pressure (BP) changes for renal denervation (RDN). Recently, novel BP response patterns have been demonstrated in animals. The current study was to verify the presence of these patterns in humans and examine the feasibility of using them to guide selective RDN. Fourteen patients with mild resistant hypertension were included in this prospective analysis. RNS was performed before and after radiofrequency-based RDN. Invasive monitoring was used continuously to obtain beat-to-beat BP. Ambulatory BP (ABP) monitoring was measured at baseline, 5–7 days, and 6–12 months, respectively. Five types of BP responses were summarized during RNS before RDN, namely: (1) BP persistently elevated; (2) BP dropped and then elevated above the baseline; (3) BP dropped and then recovered, but not over the baseline; (4) BP fluctuated in the vicinity of the baseline; and (5) BP persistently dropped. Selective RDN was performed at the site with elevated BP. The 24-h ABP decreased from 141 ± 12/94 ± 9 mmHg at baseline to 130 ± 11/85 ± 8 mmHg at 5 – 7 days (P = 0.001 for systolic BP [SBP], P = 0.003 for diastolic BP [DBP]) and 127 ± 11/85 ± 8 mmHg at 6 – 12 months (P = 0.009 for SBP, P = 0.019 for DBP). The average heart rate fell from 77 ± 8 bpm to 71 ± 5 bpm (P = 0.01) and 72 ± 7 bpm (P = 0.043), respectively. Our study showed five types of BP responses elicited by RNS in humans. RDN guided by these BP responses was feasible and resulted in obvious BP reduction, and they may potentially provide precise guidance for RDN.

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.

Hypertension significantly increases the risk of cardiovascular events and it is associated with high rates of disability and mortality. Hypertension is a common cause of cardiovascular and cerebrovascular accidents, which severely affect patients’ quality of life and lifespan. Current treatment strategies for hypertension are based primarily on medication and lifestyle interventions. The renal sympathetic nervous system plays an important role in the pathogenesis of hypertension, and catheter-based renal denervation (RDN) has provided a new concept for the treatment of hypertension. In recent years, studies on RDN have been performed worldwide. This article reviews the latest preclinical research and clinical evidence for RDN.

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.

Left atrial appendage thrombus (LAAT) is a surrogate of thromboembolic events in patients with nonvalvular atrial fibrillation (NVAF). We aimed to investigate the risk factors for LAAT formation before catheter ablation and cardioversion beside the CHA2DS2-VASc score. In this case-control study, patients with NVAF who underwent transesophageal echocardiography (TEE) were included. Demographic data, laboratory results, and echocardiographic measurements were retrospectively collected. Logistic regression analysis was performed to determine risk factors predicting LAAT. Of the 543 included patients, LAAT was identified in 50 patients (9.2%). Multivariable logistic regression analysis for the entire cohort showed that NT-proBNP (per 500 ng/L increase, OR (95% CI): 1.09 (1.00–1.19), p = 0.038) and LDL-C (per 1 mmol/L increase, OR (95% CI): 1.70 (1.05–2.77), p = 0.032) were independently correlated with the presence of LAAT after the adjustment for CHA2DS2-VASc score and anticoagulant therapy. The subgroup analysis of patients without anticoagulant therapy also yielded similar results. Regarding patients with CHA2DS2-VASc scores ≤ 1, a higher level of LDL-C (per 1 mmol/L increase, OR (95% CI): 6.31 (2.38–16.74), p < 0.001) independently correlated with the presence of LAAT. The present study suggests that beyond CHA2DS2-VASc score, raised NT-proBNP and LDL-C are additional predictors for LAAT in NVAF patients.

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.

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.