Efficacy and safety of sympathetic mapping and ablation of renal nerves for the treatment of hypertension (SMART): 6-month follow-up of a randomised, controlled trial.

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.

A case-report of chromophobe renal cell carcinoma with renal subcapsular hematoma.

INTRODUCTION AND IMPORTANCE: Chromophobe renal cell carcinoma (CHRCC) is a rare subtype of renal cancer, accompanied by subcapsular renal hematoma (SRH) without a history of traumatic or hemorrhagic disease, which is clinically rare. The reason for CHRCC with SRH may be caused by tumor rupture or vascular rupture. In the early stage, it is often asymptomatic and can be easily overlooked and misdiagnosed, leading to delayed treatment and serious consequences. CASE PRESENTATION: A 39-year-old female patient was admitted to the emergency department due to sudden dull pain and discomfort in the lower back. Subsequent ultrasound, CT, and MRI imaging examinations revealed the presence of chromophobe renal cell carcinoma with a volume of 4.5 × 3.5 × 3 cm in the middle and lower pole of the right kidney. In addition, a subcapsular hematoma with an area of approximately 6 × 11 cm was also found. The patient underwent laparoscopic radical nephrectomy. CLINICAL DISCUSSION: Due to its atypical syptmoms and signs, it is often overlooked or misdiagnosed. CHRCC has unique histological features, which distinguish it from other subtypes of renal cell carcinoma. Imaging studies such as CT scan and MRI are helpful in diagnosing and identifying associated complications. In this case, the presence of the perirenal hematoma is a notable finding, which may be caused by tumor-induced vascular disruption. CONCLUSION: This report underscores the importance of recognizing and managing complications associated with CHRCC. Early diagnosis and appropriate surgical treatment are crucial for favorable outcomes in these cases.

Variation and disparity in awareness of atrial fibrillation in China: A national cross-sectional study.

BACKGROUND: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES: The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.

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.

Collagen-Targeting Self-Assembled Nanoprobes for Multimodal Molecular Imaging and Quantification of Myocardial Fibrosis in a Rat Model of Myocardial Infarction.

Currently, inadequate early diagnostic methods hinder the prompt treatment of patients with heart failure and myocardial fibrosis. Magnetic resonance imaging is the gold standard noninvasive diagnostic method; however, its effectiveness is constrained by low resolution and challenges posed by certain patients who cannot undergo the procedure. Although enhanced computed tomography (CT) offers high resolution, challenges arise owing to the unclear differentiation between fibrotic and normal myocardial tissue. Furthermore, although echocardiography is real-time and convenient, it lacks the necessary resolution for detecting fibrotic myocardium, thus limiting its value in fibrosis detection. Inspired by the postinfarction accumulation of collagen types I and III, we developed a collagen-targeted multimodal imaging nanoplatform, CNA35-GP@NPs, comprising lipid nanoparticles (NPs), encapsulating gold nanorods (GNRs) and perfluoropentane (PFP). This platform facilitated ultrasound/photoacoustic/CT imaging of postinfarction cardiac fibrosis in a rat model of myocardial infarction (MI). The surface-modified peptide CNA35 exhibited excellent collagen fiber targeting. The strong near-infrared light absorption and substantial X-ray attenuation of the nanoplatform rendered it suitable for photoacoustic and CT imaging. In the rat model of MI, our study demonstrated that CNA35-GNR/PFP@NPs (CNA35-GP@NPs) achieved photoacoustic, ultrasound, and enhanced CT imaging of the fibrotic myocardium. Notably, the photoacoustic signal intensity positively correlated with the severity of myocardial fibrosis. Thus, this study presents a promising approach for accurately detecting and treating the fibrotic myocardium.

Cardioneuroablation for successful treatment of symptomatic bradycardia in a 12-year-old child after a 6-month follow-up.

Background: Cardioneuroablation (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. Methods: A 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. Results: First, 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. Conclusion: The 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.

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.

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.

A sham-controlled randomised trial of pulmonary artery denervation for Group 1 pulmonary arterial hypertension: one-year outcomes of the PADN-CFDA trial.

BACKGROUND: Long-term clinical outcomes after pulmonary artery denervation (PADN) in patients with Group 1 pulmonary arterial hypertension (PAH) have not been reported. AIMS: We aimed to investigate the effect of PADN on 1-year outcomes in patients with PAH. METHODS: In the multicentre PADN-CFDA trial, 128 patients with Group 1 PAH were randomly assigned to PADN plus a phosphodiesterase-5 inhibitor (PDE-5i) versus a sham PADN procedure plus a PDE-5i. The principal endpoint of interest for the present study was clinical worsening at 1 year after randomisation, the composite of worsening of PAH (increase in WHO functional class, need for additional PAH treatments or PAH-related hospitalisation), atrial septostomy, listing for lung transplantation, or all-cause death. RESULTS: One-year clinical follow-up was available in all patients. At 1 year, clinical worsening had occurred in 3 (4.8%) patients in the PADN plus PDE-5i group and in 15 patients (23.1%) in the sham plus PDE-5i group (adjusted hazard ratio: 0.17; 95% confidence interval [CI]: 0.05-0.60; p=0.006), driven by significantly increased rates of PAH-related hospitalisations, worsening functional class and the requirement for additional PAH treatments in the sham group. Results were consistent in high-risk, intermediate-risk and low-risk patients (pinteraction=0.186). Patients treated with PADN plus PDE-5i had an improvement in the between-group change in the six-minute walking distance (6MWD) from baseline to 1 year of 81.2 m (95% CI: 50.3-112.2; p<0.001) compared with PDE-5i treatment alone. CONCLUSIONS: In this multicentre sham-controlled randomised trial, PADN treatment for Group 1 PAH significantly reduced clinical worsening and improved the 6MWD during 1-year follow-up in patients treated with a PDE-5i.

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.

Treatment effects of pulmonary artery denervation for pulmonary arterial hypertension stratified by REVEAL risk score: Results from PADN-CFDA trial.

BACKGROUND: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients. METHODS: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months. RESULTS: In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up. CONCLUSIONS: In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients.

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.

Rationale and Design of Sympathetic Mapping/Ablation of Renal Nerves Trial (SMART) for the Treatment of Hypertension: a Prospective, Multicenter, Single-Blind, Randomized and Sham Procedure-Controlled Study.

Renal denervation (RDN) is proposed as a durable and patient compliance independent treatment for hypertension. However, 20-30% non-responder after RDN treatment weakened the therapeutic effect, which may be due to blind ablation. The renal nerve mapping/selective ablation system developed by SyMap Medical Ltd (Suzhou), China, has the function of mapping renal sympathetic/parasympathetic nerve sites and selectively removing renal sympathetic nerves and is expected to meet the urgent unmet clinical need of targeted RDN. The "Sympathetic Mapping/Ablation of Renal Nerves Trial" (SMART) is a prospective, multicenter, randomized, single-blinded, sham procedure-controlled trial, to evaluate the safety and efficacy of targeted renal sympathetic denervation in patients with essential and uncontrolled hypertension. The study is the first clinical registry trial using a targeted RDN for the treatment of uncontrolled hypertension; the dual-endpoint design can answer the question of how many antihypertensive drugs can be reduced in patients after RDN. The trial is registered on clinicaltrials.gov NCT02761811.

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.

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.

Evolving Role of Catheter Ablation for Atrial Fibrillation: Early and Effective Rhythm Control.

Catheter Ablation (CA) is an effective therapeutic option in treating atrial fibrillation (AF). Importantly, recent data show that CA as a rhythm control strategy not only significantly reduces AF burden, but also substantially improves clinical hard endpoints. Since AF is a progressive disease, the time of Diagnosis-to-Intervention appears crucial. Recent evidence shows that earlier rhythm control is associated with a lower risk of adverse cardiovascular outcomes in patients with early AF. Particularly, CA as an initial first line rhythm control strategy is associated with significant reduction of arrhythmia recurrence and rehospitalization in patients with paroxysmal AF. CA is shown to significantly lower the risk of progression from paroxysmal AF to persistent AF. When treating persistent AF, the overall clinical success after ablation remains unsatisfactory, however the ablation outcome in patients with "early" persistent AF appears better than those with "late" persistent AF. "Adjunctive" ablation on top of pulmonary vein isolation (PVI), e.g., ablation of atrial low voltage area, left atrial posterior wall, vein of Marshall, left atrial appendage, etc., may further reduce arrhythmia recurrence in selected patient group. New ablation concepts or new ablation technologies have been developing to optimize therapeutic effects or safety profile and may ultimately improve the clinical outcome.

A medical image segmentation method based on multi-dimensional statistical features.

Medical image segmentation has important auxiliary significance for clinical diagnosis and treatment. Most of existing medical image segmentation solutions adopt convolutional neural networks (CNNs). Althought these existing solutions can achieve good image segmentation performance, CNNs focus on local information and ignore global image information. Since Transformer can encode the whole image, it has good global modeling ability and is effective for the extraction of global information. Therefore, this paper proposes a hybrid feature extraction network, into which CNNs and Transformer are integrated to utilize their advantages in feature extraction. To enhance low-dimensional texture features, this paper also proposes a multi-dimensional statistical feature extraction module to fully fuse the features extracted by CNNs and Transformer and enhance the segmentation performance of medical images. The experimental results confirm that the proposed method achieves better results in brain tumor segmentation and ventricle segmentation than state-of-the-art solutions.

Activation of TRPV4 by lactate as a critical mediator of renal fibrosis in spontaneously hypertensive rats after moderate- and high-intensity exercise.

Moderate-intensity exercise training has been regarded a healthy way to alleviate kidney fibrosis by the transforming growth factor-beta (TGFß) signaling pathway. However, the impact of different intensity exercise training on renal function is unknown, and the underlying mechanism is also unclear. The purpose of this study is to explore the effect of lactic acid in different intensity exercise training on renal fibrosis in spontaneous hypertension. Masson's trichrome staining, immunohistochemistry, lactic acid kit, and Western blotting were applied on the excised renal tissue from six male Wistar-Kyoto rats (WKY) and 18 male spontaneously hypertensive rats (SHR), which were randomly divided into a sedentary hypertensive group (SHR), moderate-intensity exercise hypertensive group (SHR-M), and high-intensity exercise hypertensive group (SHR-H). The results revealed that renal and blood lactic acid, as well as the key fibrotic protein levels of transient receptor potential vanilloid 4 (TRPV4), TGFß-1, phospho-Smad2/3 (p-Smad2/3), and connective tissue growth factor (CTGF), were significantly decreased in the SHR-M group when compared with the SHR and SHR-H groups. In further in vitro experiments, we selected normal rat kidney interstitial fibroblast (NRK-49F) cells. By immunofluorescence and Western blotting techniques, we found that TRPV4 antagonists (RN-1734) markedly inhibited lactate-induced fibrosis. In conclusion, compared with previous studies, high-intensity exercise training (HIET) can cause adverse effects (renal damage and fibrosis). High concentrations of lactic acid can aggravate renal fibrosis conditions via activating TRPV4-TGFß1-SMAD2/3-CTGF-mediated renal fibrotic pathways in spontaneous hypertension. This finding might provide new ideas for treating hypertensive nephropathy with different intensity exercise in the future.