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.

Estimated Pulse Wave Velocity Predicts All-Cause and Cardiovascular-Cause Mortality in Individuals With Hypertension　- Findings From a National Health and Nutrition Examination Study 1999-2018.

BACKGROUND: This study aimed to investigate the association between estimated pulse wave velocity (ePWV) and mortality outcomes among individuals with hypertension.Methods and Results: Based on the National Health and Nutrition Examination Survey (NHANES) 1999-2018, a total of 14,396 eligible participants with hypertension were enrolled. The ePWV was calculated using the equation based on blood pressure and age. The mortality outcomes of included participants were directly acquired from the National Death Index database. The multivariable Cox regression analysis was used to examine the relationship between ePWV and mortality outcomes. Moreover, the restricted cubic spline (RCS) was also used to explore this relationship. Receiver operating characteristics curves (ROC) were adopted to evaluate the prognostic ability of ePWV for predicting mortality outcomes of patients with hypertension. The median follow-up duration was 10.8 years; individuals with higher an ePWV had higher risks of mortality from both all causes (HR: 2.79, 95% CI: 2.43-3.20) and cardiovascular diseases (HR: 3.41, 95% CI: 2.50-4.64). After adjusting for confounding factors, each 1 m/s increase in ePWV was associated with a 43% increase in all-cause mortality risk (HR: 1.43, 95% CI: 1.37-1.48) and a 54% increase in cardiovascular mortality risk (HR: 1.54, 95% CI: 1.43-1.66). CONCLUSIONS: This study indicates that ePWV is a novel prognostic indicator for predicting the risks of mortality among patients with hypertension.

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.

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

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

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

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

Radiomics of CTA is feasible in identifying muscle ischemia.

BACKGROUND: Advanced models based on computed tomography angiography (CTA) radiomics features in discriminating muscle ischemia from normal condition are lacking. PURPOSE: To investigate the feasibility of radiomics of CTA in discriminating ischemic muscle from normal muscle. MATERIAL AND METHODS: A total of 102 patients (51 ischemia and 51 non-ischemia) were analyzed using a CTA radiomics method. The radiomics features of muscle were compared between ischemic and normal cases. The maximum relevance minimum redundancy (mRMR) algorithm and least absolute shrinkage and selection operator (LASSO) logistic regression model were used. The receiver operating characteristic (ROC) curve was used to determine the performance of radiomics signature. RESULTS: Thirty-nine CTA radiomics features were significantly different between the two groups (P < 0.05). By LASSO, six features were used to construct a model. The signature area under the curve was 0.92 and 0.91 in the training and validation cohorts, respectively. The sensitivity and specificity of the signature were 92% and 86% for the training cohort, and 80% and 94% for the validation cohort, respectively. CONCLUSION: CTA radiomics signature is useful in identifying ischemic muscle in selected patients.

Involvement of pyroptosis pathway in epicardial adipose tissue - myocardium axis in experimental heart failure with preserved ejection fraction.

Epicardial adipose tissue (EAT) is a metabolically active organ which generates inflammatory cytokines. Thickness of EAT is associated with onset and development of heart failure with preserved ejection fraction (HFpEF). However, it is still unclear the specific mechanisms and pharmacological targets on EAT induced inflammation in HFpEF. A two-hit protocol with western diet and Nω-nitrol-arginine methyl ester (L-NAME) was used to establish HFpEF mouse model. In HFpEF mice, inflammatory biomarkers, such as tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and von willebrand factor (vWF) elevated in myocardium compared to control. Inflammatory cell infiltration in myocardium was increased. In HFpEF mice, inflammasome-mediated pyroptosis pathway was activated in the EAT. Suppression of pyroptosis-related protein gasdermin D (GSDMD) in cultured EAT could lower cardiomyocyte inflammation and autophagy. Furthermore, spironolactone and rosuvastatin, the two-hit anti-inflammatory agents, reduced NLR family pyrin domain containing 3 (NLRP3)/GSDMD pyroptosis in EAT and autophagy in myocardium of HFpEF mouse. The combination treatment also enhanced exercise tolerance and appeased inflammatory injuries in HFpEF mice. CONCLUSION: Pyroptosis signaling is involved in EAT-myocardium axis in mouse model of HFpEF. Targeting adipocyte-derived inflammation in EAT bears potential to treatment HFpEF.

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.

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

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

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

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

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

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

Association of clinical predictors with recurrence of atrial fibrillation after catheter ablation.

BACKGROUND: Recurrence rate after radiofrequency catheter ablation (RFCA) remains high, and further investigation on predictors of recurrence is needed. OBJECTS: To identify risk factors of atrial fibrillation (AF) recurrence in patients undergoing RFCA. METHODS: We retrospectively studied 257 patients with AF who underwent RFCA preceded by transthoracic echocardiographic and pulmonary vein CT examination from 2016 to 2019. Electrocardiogram examination was performed at baseline, 1, 3, 6 months, and 1 year after RFCA. We divided patients into two groups based on AF recurrence including recurrence group (n = 79) and nonrecurrence group (n = 178). The crude and independent association between clinical variables and AF recurrence was evaluated with logistic regression analysis. Specificity and positive predictive value of relevant factors for AF recurrence were performed by ROC curve. RESULTS: Of these AF patients, 174 (68%) was paroxysmal AF and 83 (32%) was persistent AF. The multivariate logistic regression demonstrated that AF duration (OR = 1.008, 95% CI 1.002-1.013, p = .008), pulmonary arterial hypertension (PAH; OR = 2.313, 95% CI 1.031-5.192, p = .042), and low-density lipoprotein cholesterol (LDL-C; OR = 1.646, 95% CI 1.129-2.398, p = .010) were independently correlated with recurrence of AF. For predicting AF recurrence, the specificity and sensitivity of AF duration were 30.1% and 87.3%, and for LDL-C, the specificity and sensitivity of AF duration were 60.6% and 60.5%, respectively. CONCLUSIONS: Atrial fibrillation duration, PAH, and LDL-C might be independent risk factors for the recurrence of AF after RFCA.

Herceptin-decorated paclitaxel-loaded poly(lactide-co-glycolide) nanobubbles: ultrasound-facilitated release and targeted accumulation in breast cancers.

Ultrasound can promote the drug release from drug-loaded substances and alter the tumor local microenvironment to facilitate the transport of drug carriers into the tumor tissues. Based on the altered tumor microenvironment, nanobubbles (NBs) as drug carriers with surfaces functionalized with targeting ligands can reach the tumor sites, thereby increasing the efficacy of chemotherapy. Herein, paclitaxel (PTX)-loaded poly(lactide-co-glycolide) (PLGA) NBs are prepared as drug carriers with covalently conjugated herceptin (anti-HER2 monoclonal antibody) on the surface to guide the target. The effect of ultrasound on the drug release and targeting of the herceptin-conjugated drug-loaded nanobubbles (PTX-NBs-HER) on the cancerous cells is determined. The use of ultrasound significantly improves the cell targeting capability in vitro, and efficiency of enhanced permeability and retention in vivo. The combination of PTX-NBs-HER and ultrasound facilitates the release of PTX, as well as the uptake and cell apoptosis in vitro. The in vivo application of both PTX-NBs-HER and ultrasound enhances the PTX targeting and accumulation in breast cancers while reducing the transmission and distribution of PTX in healthy organs. The combination of ultrasound with PTX-NBs-HER as contrast agents and drug carriers affords an image-guided drug delivery system for the precise targeted therapy of tumors.

The Role of Angle in the Evaluation of Ablation Accuracy in Pulmonary Vein Isolation Navigated by Image Integration.

BACKGROUND: The conventional index for ablation accuracy is to compare the distance between mapping points with and without treatment by using image integration. We attempted to quantitatively evaluate the role of angle as an index in the ablation accuracy in patients with atrial fibrillation (AF). METHODS: A total of 48 patients with AF were included in the present study. Virtual fluoroscopy planes were predicted by pulmonary vein (PV) angiography, and the standard image planes were defined on the basis of the computed tomography images. Ablations were performed, guided by image integration; and the ablation planes were defined by the actual ablation rings. The predicted angle (distance) was defined as the angle (distance) between the fluoroscopy (predicted) plane and image (standard) plane, whereas the actual angle (distance) was defined as the angle (distance) between the ablation (actual) planes and the image (standard) planes. RESULTS: We found that all actual angles were significantly smaller than the predicted angles (P <.05), but only the actual distances in the left PV, right inferior PV, right superior PV, and right PV were significantly smaller; the distances in the left inferior PV and left superior PV were not significantly different (P >.05). CONCLUSION: Our finding indicates that both the angle and the distance can be significantly reduced by navigation with image integration, but that the angle exhibited better sensitivity than the conventional index of distance. We suggest that the angle should be considered as a new index for ablation accuracy.

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.

Global, regional, and national burden of atrial fibrillation/flutter related to metabolic risks over three decades: estimates from the global burden of disease study 2019.

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 (GBD) study 2019. METHODS & RESULTS: The analysis of disease burden focused on numbers, age-standardized rates (ASR) of deaths, disability-adjusted life years (DALYs), and estimated annual percentage change (EAPC), 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. CONCLUSIONS: The global AF/AFL burden related to metabolic risks has significantly increased over 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.

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.

HFpEF as systemic disease, insight from a diagnostic prediction model reminiscent of systemic inflammation and organ interaction in HFpEF patients.

Systemic inflammation and reciprocal organ interactions are associated with the pathophysiology of heart failure with preserved ejection fraction (HFpEF). However, the clinical value, especially the diagnositc prediction power of inflammation and extra-cardiac organ dysfunction for HfpEF is not explored. In this cross-sectional study, 1808 hospitalized patients from January 2014 to June 2022 in ChiHFpEF cohort were totally enrolled according to inclusion and exclusion criteria. A diagnostic model with markers from routine blood test as well as liver and renal dysfunction for HFpEF was developed using data from ChiHFpEF-cohort by logistic regression and assessed by receiver operating characteristic curve (ROC) and Brier score. Then, the model was validated by the tenfold cross-validation and presented as nomogram and a web-based online risk calculator as well. Multivariate and LASSO regression analysis revealed that age, hemoglobin, neutrophil to lymphocyte ratio, AST/ALT ratio, creatinine, uric acid, atrial fibrillation, and pulmonary hypertension were associated with HFpEF. The predictive model exhibited reasonably accurate discrimination (ROC, 0.753, 95% CI 0.732-0.772) and calibration (Brier score was 0.200). Subsequent internal validation showed good discrimination and calibration (AUC = 0.750, Brier score was 0.202). In additoin to participating in pathophysiology of HFpEF, inflammation and multi-organ interactions have diagnostic prediction value for HFpEF. Screening and optimizing biomarkers of inflammation and multi-organ interactions stand for a new field to improve noninvasive diagnostic tool for HFpEF.