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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 Conclusion CTA radiomics signature is useful in identifying ischemic muscle in selected patients.

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.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.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.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.

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.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.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.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.

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 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.

Aims Anticoagulation for atrial fibrillation patients with liver disease represents a clinical dilemma. We sought to evaluate the efficacy/safety of different anticoagulation, i.e. vitamin K antagonist (VKA) and non-VKA oral anticoagulants (NOACs) in such patient group. Methods and results This was a pooled-analysis enrolling up-to-date clinical data. Two subsets: subset A (VKA vs. Non-Anticoagulation) and subset B (NOACs vs. VKA) were pre-specified. The study outcomes were ischaemic stroke (IS)/thromboembolism (TE), major bleeding (MB), intracranial bleeding (ICB), gastrointestinal bleeding (GIB), and all-cause mortality. A total of 20 042 patients’ data were analysed (subset A: N = 10 275, subset B: N = 9767). Overall mean age: 71 ± 11 years, mean CHA2DS2-VASc score: 4.0 ± 1.8, mean HAS-BLED score: 3.6 ± 1.2. The majority of the patients had Child-Pugh category (A-B). As compared with Non-Anticoagulation, VKA seemed to reduce the risk of IS/TE [odds ratio (OR): 0.60, P = 0.05], but heighten the risk of all-bleeding events including MB (OR: 2.81, P = 0.01), ICB (OR: 1.60, P = 0.01), and GIB (OR: 3.32, P = 0.01). When compared with VKA, NOACs had similar efficacy in reducing the risk of IS/TE (OR: 0.82, P = 0.64), significantly lower risk of MB (OR: 0.54, P = 0.0003) and ICB (OR: 0.35, P Conclusions VKA appears to reduce the risk of IS/TE but increase all-bleeding events. NOACs have similar effect in reducing the risk of IS/TE and have significantly lower risk of MB and ICB as compared with VKA. NOACs seem to be associated with better clinical outcome than VKA in patients with mild–moderate liver disease.

Background Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery, resulting in an increased risk of morbidity and longer hospital stay. Pharmacologic prophylaxis has been recommended to improve the outcome in patients at high risk of developing POAF after cardiac surgery. Several studies have applied the CHA2DS2-VASc (Congestive heart failure, Hypertension Age [≥65 = 1 point, ≥75 = 2 points], Diabetes, and Stroke/transient ischemic attack (2 points)–vascular disease [peripheral arterial disease, previous myocardial infarction, aortic atheroma]) score in the risk stratification of POAF but yielded contradicting results. This study aims to determine the association between CHA2DS2-VASc score and POAF and further to explore its discriminative ability for the prediction of POAF. Methods We systematically searched the Medline, Embase, Cochrane library, and other data sources with key terms “CHA2DS2-VASc,” “atrial fibrillation,” and “cardiac surgery.” Studies designed for CHA2DS2-VASc score in stratifying the risks of POAF in patients undergoing cardiac surgery were included. Statistical analyses were performed with R 3.5.1 and STATA 13.0. Results Seven hundred twenty-one studies were identified, of which 12 studies with 18,086 patients were finally included in our analysis. The CHA2DS2-VASc score was found to be an independent predictor of POAF after cardiac surgery (odds ratio, 1.46; 95% confidence interval [CI], 1.25-1.72) and exhibited a relatively strong specificity (0.70; 95% CI, 0.61-0.78) and sensitivity (0.72; 95% CI, 0.54-0.85) for predicting POAF. The bivariate model-based pooled area under the receiver operating curve was estimated to be 0.76 (95% CI, 0.72-0.79). Conclusions The CHA2DS2-VASc score has relatively good performance in predicting POAF after cardiac surgery and may help identify the patients at high risk of POAF.

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.

It focused on clinical effects of individualized nursing and health education (INHE) on patients with diabetes mellitus type 2 (T2DM) and hypertension. 68 patients were randomly rolled into two groups, 34 cases in the control group (group A) received routine nursing and remaining 34 cases in the experimental group (group B) received INHE. The disease knowledge mastery (DKM) and the effect of rehabilitation nursing of patients were compared. The results suggested that DKM of patients in group B was obviously greater (P < 0.05). The total effective rate (TER) in group B was 91.45%, which was observably greater than that (76.35%) in group A (P < 0.05). After nursing, the fasting plasma glucose (FPG), 2-hour postprandial glucose (2h PG), systolic blood pressure (SBP), and diastolic blood pressure (DBP) levels of all patients decreased, and those in group B were much lower (P < 0.05). Scores of the Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) of the two groups were 56.34 ± 8.12 points and 56.33 ± 8.01 points in group A, respectively; and those in group B were 42.52 ± 6.77 points and 41.71 ± 7.23 points, respectively; and they were all decreased and those in the group B were obviously smaller (P < 0.05). In summary, INHE can effectively improve the psychological cognition of patients with T2DM and hypertension and strengthen the control of blood pressure and blood sugar.

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.

This study evaluated the role of adjunctive left atrium posterior wall isolation (PWI) in preventing atrial fibrillation (AF) recurrence.The left atrium posterior wall is an arrhythmogenic substrate that contributes to the development of AF.This was an updated pooled analysis that included clinical data regarding PWI plus pulmonary vein isolation (PVI) in treating AF. The primary outcome was recurrence of atrial tachyarrhythmias.A total of 26 studies with 3,287 patients with AF (age 61.7 ± 10.8 years) were included. Mean follow-up was 15.2 ± 8.4 months. Procedural success to achieve PWI was 92.8%. In paroxysmal AF, adjunctive PWI did not reduce the recurrence of all atrial arrhythmias (P = 0.21) or AF (P = 0.37); however, in persistent AF, adjunctive PWI was associated with substantially lower recurrence of all atrial arrhythmias (risk ratio: 0.74; P 0.001) and AF (risk ratio: 0.67; P = 0.01), particularly when randomized data were included. Subgroup analyses based on meta-regression demonstrated that patients with older age, a larger left atrial diameter, and persistent AF benefited more significantly from the adjunctive PWI. Adjunctive PWI using either radiofrequency or a cryoballoon reduced AF recurrence, whereas using radiofrequency seemed to be associated with higher recurrence rate of atrial tachycardias and/or atrial flutter. Non-BOX adjunctive PWI rather than BOX PWI was associated with significantly lower recurrence of AF. The incidence of procedural adverse events between the PVI+PWI (3.2%) and PVI (2.8%) groups was low and similar. PVI+PWI needed longer ablation and/or procedural time but had similar fluoroscopy time.Adjunctive PWI can be achieved in most patients without compromising safety. Patients with persistent AF appear to benefit from this approach. The ablation technology and/or approach may affect the clinical outcome of PWI.

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites ( P =0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine ( P =0.004 for tyrosine hydroxylase, P =0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites ( P =0.012 for total area and P R =0.649; P =0.012 and R =0.643; P =0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks ( R =0.837, P R =0.927, P

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 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.

Transcatheter left atrial appendage occlusion (LAAO) is non-inferior to vitamin K antagonists (VKAs) in preventing thromboembolic events in atrial fibrillation (AF). Non-vitamin K antagonists (NOACs) have an improved safety profile over VKAs, however, evidence regarding their effect on cardiovascular and neurological outcomes relative to LAAO is limited. Up-to-date randomized trials or propensity-score-matched data comparing LAAO vs. NOACs in high-risk patients with AF were pooled in our study. A total of 2849 AF patients (LAAO: 1368, NOACs: 1481, mean age: 75 ± 7.5 yrs, 63.5% male) were enrolled. The mean CHA2DS2-VASc score was 4.3 ± 1.7, and the mean HAS-BLED score was 3.4 ± 1.2. The baseline characteristics were comparable between the two groups. In the LAAO group, the success rate of device implantation was 98.8%. During a mean follow-up of 2 years, as compared with NOACs, LAAO was associated with a significant reduction of ISTH major bleeding (p = 0.0002). There were no significant differences in terms of ischemic stroke (p = 0.61), ischemic stroke/thromboembolism (p = 0.63), ISTH major and clinically relevant minor bleeding (p = 0.73), cardiovascular death (p = 0.63), and all-cause mortality (p = 0.71). There was a trend toward reduction of combined major cardiovascular and neurological endpoints in the LAAO group (OR: 0.84, 95% CI: 0.64–1.11, p = 0.12). In conclusion, for high-risk AF patients, LAAO is associated with a significant reduction of ISTH major bleeding without increased ischemic events, as compared to “contemporary NOACs”. The present data show the superior role of LAAO over NOACs among high-risk AF patients in terms of reduction of major bleeding, however, more randomized controlled trials are warranted.

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.

At present, MRI is the primary choice of examination for the diagnosis of thoracic extramedullary hemopoiesis. When thoracic extramedullary hemopoiesis presents as posterior mediastinum masses in specific clinical contexts, the diagnosis is not challenging. Other radiological presentations may be more difficult for diagnosis and require biopsy. Needle biopsy is typically preferred for the diagnosis of extramedullary hemopoiesis however, the high vascularization of tissues is one of the complications of this method thus, it is avoided. The aim of the present study was to compare the diagnostic parameters of CT with MRI for the diagnosis of thoracic extramedullary hemopoiesis in patients with leukemia, with an open lung biopsy as a reference standard. Chest CT, chest MRI and open lung biopsy data from a total of 912 patients with leukemia with a sign(s) and symptoms of suspected paravertebral and/or pulmonary extramedullary hemopoiesis were reviewed. In the present study, thoracic extramedullary hemopoiesis was defined as diffusivity of both lung fields being increased compared with the blood pool and no other abnormal focal of lungs being increased compared with the blood pool. The beneficial score was calculated for CT and MRI and plotted for the decision making of irradiation. With respect to open lung biopsy, MRI had a higher sensitivity compared with CT (0.865 vs. 0.809; P

Heart failure (HF) has been proposed as a potential indication of renal denervation (RDN). However, the mechanisms enabling RDN to attenuate HF are not well understood, especially the central effects of RDN. The aim of this study was to decipher the mode of operation of RDN in the treatment of HF using a canine model of right ventricular rapid pacing-induced HF. Accordingly, 24 Chinese Kunming dogs were randomly grouped to receive sham procedure (sham-operated group), bilateral RDN (RDN group), rapid pacing to induce HF (HF-control group), and bilateral RDN plus rapid pacing (RDN + HF group). Echocardiography, plasma brain natriuretic peptide (BNP), and norepinephrine (NE) concentrations of randomized dogs were measured at baseline and 4 weeks after interventions, followed by histological and molecular analyses. Twenty dogs completed the research successfully and were enrolled for data analyses. Results showed that the average optical density of renal efferent and afferent nerves were significantly lower in the RDN and RDN + HF groups than in the sham-operated group, with a significant reduction of renal NE concentration. Rapid pacing in the RDN + HF and HF-control groups, compared with the sham-operated group, induced a significant increase in left ventricular end-diastolic volume and decrease in left ventricular ejection fraction and correspondingly resulted in cardiac fibrosis and dysfunction. Cardiac fibrosis evaluated by Masson's trichrome staining and the expression of transforming growth factor-β1 (TGF-β1) were significantly higher in the HF-control group than in the sham-operated group, which were remarkably attenuated by the application of the RDN technique in the RDN + HF group. In terms of central renin-angiotensin system (RAS), the expression of angiotensin II (AngII)/angiotensin-converting enzyme (ACE)/AngII type 1 receptor (AT1R) in the hypothalamus of dogs in the HF-control group, compared with the sham-operated group, was upregulated and that of the angiotensin-(1-7) [Ang-(1-7)]/ACE2 was downregulated. Furthermore, both of them were significantly attenuated by the RDN therapy in the RDN + HF group. In conclusion, the RDN technique could damage renal nerves and suppress the cardiac remodeling procedure in canine with HF while concomitantly attenuating the overactivity of central RAS in the hypothalamus.

BACKGROUND Previous studies showed that radiofrequency energy delivery of the renal artery could induce an immediate and substantial blood pressure (BP)-elevation response, which might be indicative of the increase in central sympathetic nervous activity. OBJECTIVE The current study was to investigate whether the presence of BP-elevation response to radiofrequency energy delivery can serve as a surrogate to predict BP reduction following renal artery sympathetic denervation (RDN). METHOD Data were collected on 67 patients undergoing RDN for drug-resistant hypertension. The BP-elevation response to radiofrequency application was defined as elevation of SBP by at least 10 mmHg during radiofrequency energy delivery. The extent of BP reduction at 1, 3, 6, 12 months after RDN were analyzed. Multivariable linear regression analysis of baseline and procedural characteristics was performed to identify the determinants of BP reduction after RDN. RESULTS Ten patients (14.9%) were classified as nonresponders to radiofrequency delivery and showed significantly lower BP reduction compared with responders. The SBP reductions of radiofrequency delivery responders vs. nonresponders were 31.2 ± 8.6 vs. 11.4 ± 8.6 mmHg, 36.3 ± 10.0 vs. 14.6 ± 10.6 mmHg, 39.9 ± 9.9 vs. 15.2 ± 8.8 mmHg, and 40.0 ± 8.7/13.5 ± 5.8 mmHg (P

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

Background Renin-angiotensin-system inhibitors (RASIs) have been suggested as an upstream therapy for selected AF patients; however, the evidence in surgical setting is limited. Objective We aimed to evaluate the role of preoperative RASIs in prevention of postoperative atrial fibrillation (POAF) and adverse events for patients undergoing cardiac surgery. Methods In this collaborative pooled-analysis, both randomized and nonrandomized controlled trials comparing preoperative RASIs with no preoperative RASIs treatment on the incidence of POAF were identified. Sensitivity and subgroup analyses of RCTs were performed to test the stability of the overall-effect, and meta-regression to explore the potential risk of bias. The primary outcome was POAF, and the secondary outcomes includes rate of stroke, mortality and duration of hospitalization. Results Eleven trials involving 27885 patients (male 74%, median age 65yrs) were included. As compared to the control group, preoperative RASIs did not significantly reduce the risk of POAF (OR: 1.04, 95% CI: 0.91–1.19), stroke (OR: 0.86, 95% CI: 0.62–1.19), death (OR: 1.07, 95% CI: 0.85–1.35), composite adverse cardiac events (OR: 1.04, 95% CI: 0.91–1.18), and hospital stay (WMD: −0.04, 95% CI: −1.05 to 0.98). Pooled-analysis of randomized trials showed consistent results. The primary overall-effect was maintained in sensitivity and subgroup analyses. Meta-regression showed that male-gender was a significant risk-factor of POAF and use of Beta-blockers was associated with a significantly reduced risk in developing POAF. Conclusion and relevance This study demonstrates that preoperative RASIs do not offer additional benefit in reducing the risk of postoperative AF, stroke, death and hospitalization in the setting of cardiac surgery. The results provide no support for use of RASIs for the prevention of POAF and adverse events in patients undergoing cardiac surgery.

Renal nerve stimulation (RNS) can result in substantial blood pressure (BP) elevation, and the change was significantly blunted when repeated stimulation after ablation. However, whether RNS could provide a meaningful renal nerve mapping for identification of optimal ablation targets in renal denervation (RDN) is not fully clear. Here, we compared the antihypertensive effects of selective RDN guided by two different BP responses to RNS and explored the nerve innervations at these sites in Kunming dogs. Our data indicated that ablation at strong-response sites showed a more systolic BP-lowering effect than at weak-response sites (P=0.002), as well as lower levels of tyrosine hydroxylase and norepinephrine in kidney and a greater reduction in plasma norepinephrine (P=0.004 for tyrosine hydroxylase, P=0.002 for both renal and plasma norepinephrine). Strong-response sites showed a greater total area and mean number of renal nerves than weak-response sites (P=0.012 for total area and P0.001 for mean number). Systolic BP-elevation response to RNS before RDN and blunted systolic BP-elevation to RNS after RDN were correlated with systolic BP changes at 4 weeks follow-up (R=0.649; P=0.012 and R=0.643; P=0.013). Changes of plasma norepinephrine and renal norepinephrine levels at 4 weeks were also correlated with systolic BP changes at 4 weeks (R=0.837, P0.001 and R=0.927, P0.001). These data suggest that selective RDN at sites with strong BP-elevation response to RNS could lead to a more efficient RDN. RNS is an effective method to identify the nerve-enriched area during RDN procedure and improve the efficacy of RDN.

Myocardial fibrosis plays an important role in the development of heart failure and malignant arrhythmia, which potentially increases the incidence of sudden cardiac death. Therefore, early detection of myocardial fibrosis is of great significance for evaluating the prognosis of patients and formulating appropriate treatment strategies. Late gadolinium enhanced magnetic resonance imaging is considered as the currently effective strategy for noninvasive detection of myocardial fibrosis, but it still suffers from some critical issues. In this work, multifunctional CNA35-labeled perfluoropentane nanoparticles (CNA35-PFP NPs) have been elaborately designed and constructed for molecular imaging of fibrotic myocardium based on ultrasound imaging. These as-constructed CNA35-PFP NPs are intravenously infused into rabbit circulation with an animal model of myocardial infarction. Especially, these targeted CNA35-PFP NPs with nanoscale size could efficiently pass through the endothelial cell gap and adhere to the surface of fibroblasts in the fibrotic myocardium. Importantly, followed by low-intensity focused ultrasound irradiation on the myocardium, these intriguing CNA35-PFP NPs could transform from liquid into gaseous microbubbles, which further significantly enhanced the ultrasound contrast in the fibrotic area, facilitating the detection by diagnostic ultrasound imaging. Therefore, this work provides a desirable noninvasive, economical, and real-time imaging technique for the assessment of cardiac fibrosis with diagnostic ultrasound based on the rational design of liquid-to-gas phase-changeable nanoplatforms.

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery, resulting in an increased risk of morbidity and longer hospital stay. Pharmacologic prophylaxis has been recommended to improve the outcome in patients at high risk of developing POAF after cardiac surgery. Several studies have applied the CHAWe systematically searched the Medline, Embase, Cochrane library, and other data sources with key terms "CHASeven hundred twenty-one studies were identified, of which 12 studies with 18,086 patients were finally included in our analysis. The CHAThe CHA

The Supplemental Materials of pre-peer review manuscript submitted to American Journal of Physiology-Heart and Circulatory Physiology.

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

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).

Background: The effect of catheter ablation (CA) versus drug therapy on cardiac function improvement is not clear for patients with persistent atrial fibrillation and heart failure. To compare the short-term therapeutic effects between CA and conventional drug therapy, we conducted a meta-analysis of the current randomized controlled trials (RCTs). Objective and method: The analyses systematically collected PubMed, Embase, and the Cochrane Library for RCTs comparing catheter ablation with medical therapy in patients with persistent atrial fibrillation and heart failure. In order to reduce the impact of other factors on cardiac function, we limited the maximum follow-up time to two years. The primary outcome is changes in left ventricular ejection fraction (LEVF), second outcomes are changes in 6-minute walk test (6MWT), Minnesota Living with Heart Failure Score (MLHFQ), B-type natriuretic peptide (BNP). SMD was used for the results measured by different methods. Random-effects model or fixed-effects model was used to estimate relative risks (RRs) with 95% confidence intervals (CIs). Results: A total of six randomized controlled trials included 775 patients included in the final analysis, compared with drug therapy, catheter ablation has a better improvement in left ventricular ejection fraction (SMD, 0.57; 95% CI [0.40, 0.94], p

Background: The present study was to evaluate the value of CHADS2 and CHA2DS2VASC scores on predicting left atrial (LA) or left atrial appendage (LAA) thrombus in atrial fibrillation (AF) patients prior to ablation. Methods and results: A total of 397 patients with nonvalvular AF were analyzed to determine the relationship between CHADS2 and CHA2DS2VASC scores and LA/LAA thrombus identified on transesophageal echocardiography prior to ablation. LA/LAA thrombus was present in 38 patients (9.6%). There was a strong association between CHADS2 score or CHA2DS2VASC score and LA/LAA thrombus. No thrombus was identified in patients with CHA2DS2VASC score of 0 regardless of anticoagulation status. However, LA/LAA thrombus was detected in 2.9% patients with CHADS2 score of 0 without adequate anticoagulation, while no thrombus was present in the patients with CHADS2 score of 0 with adequate anticoagulation. Univariate analysis showed that heart failure (LVEF50%), LA ≥ 40 mm, diabetes mellitus, previous stroke or TIA, CAD, hypertension, inadequate coumadin therapy, CHADS2 score of ≥ 2 and CHA2DS2VASC score of ≥ 2 were significantly associated with LA/LAA thrombus. Multivariable Cox regression analysis demonstrated that CHA2DS2VASC score of ≥ 2 (p=0.02) and previous stroke or TIA (p=0.04) were independently associated with LA/LAA thrombus regardless of anticoagulation status. ROC curve analysis showed that CHADS2 score and CHA2DS2VASC score could be similarly used to predict the presence of LA thrombus. Conclusion: Both CHA2DS2VASC and CHADS2 scores were associated with LA/LAA thrombus in non-valvular AF patients. Although CHA2DS2VASC score and CHADS2 score had similar value to predict LA/LAA thrombus, CHA2DS2VASc score was better to identify low-risk patients for LA/LAA thrombus than CHADS2 score without anticoagulation. It seemed safe to perform AF ablation or cardio version in AF patients with a CHA2DS2VASC of 0 without TEE or anticoagulation therapy.

Importance Postoperative atrial fibrillation (POAF) is a well-known complication after cardiac surgery. Renin-angiotensin system inhibitors (RASIs) have been suggested as an upstream therapy for selected patients with AF; however, evidence in the surgical setting is limited. Objective To evaluate the role of preoperative RASIs in prevention of POAF and adverse events for patients undergoing cardiac surgery. Data Sources The PubMed database and the Cochrane Library from inception until December 31, 2018, were searched by using the keywordsrenin-angiotensin system inhibitorsORangiotensin-converting enzyme inhibitorsORangiotensin receptor blockerORaldosterone antagonistANDcardiac surgery. ClinicalTrials.gov was searched from inception until December 31, 2018, by using the keywordspostoperative atrial fibrillation. Study Selection Randomized clinical trials (RCTs) and observational studies comparing the association between preoperative RASI treatment vs no preoperative RASI treatment (control group) and the incidence of POAF were identified. Eleven unique studies met the selection criteria. Data Extraction and Synthesis Pooled analysis was performed using a random-effects model. Sensitivity and subgroup analyses of RCTs were performed to test the stability of the overall effect. Metaregression was conducted to explore potential risk of bias. Main Outcomes and Measures The primary outcome was POAF, and the secondary outcomes included rates of stroke and mortality and duration of hospitalization. Results Eleven unique studies involving 27 885 unique patients (74.4% male; median age, 65 years [range, 58.5-74.5 years]) were included. Compared with the control group, the RASI group did not have a significantly reduced risk of POAF (odds ratio [OR], 1.04; 95% CI, 0.91-1.19;P = .55;z = 0.60), stroke (OR, 0.86; 95% CI, 0.62-1.19;P = .37;z = 0.90; without significant heterogeneity,P = .11), death (OR, 1.07; 95% CI, 0.85-1.35;P = .56;z = 0.59; without significant heterogeneity,P = .12), composite adverse cardiac events (OR, 1.04; 95% CI, 0.91-1.18;P = .58;z = 0.56), or a reduced hospital stay (weighted mean difference, −0.04; 95% CI, −1.05 to 0.98;P = .94;z = 0.07) using a random-effects model. Pooled analysis focusing on RCTs showed consistent results. The primary overall effect was maintained in sensitivity and subgroup analyses. Metaregression showed that male sex was significantly associated with POAF (τ2 = 0.0065;z = 3.47;Q = 12.047;P Conclusions and Relevance The findings from this study suggest that preoperative RASI treatment does not offer additional benefit in reducing the risk of POAF, stroke, death, and hospitalization in the setting of cardiac surgery. The results provide no support for conventional use of RASIs for the possible prevention of POAF and adverse events in patients undergoing cardiac surgery; further randomized data, particularly among those patients with heart failure, are needed.

The myocardial microenvironment plays a decisive role in the survival, migration and differentiation of stem cells. We studied myocardial micro-environmental changes induced by ultrasound-targeted microbubble destruction (UTMD) and their influence on the transplantation of mesenchymal stem cells (MSCs). Various intensities of ultrasound were applied to the anterior chest in canines with myocardial infarction after intravenous injection of microbubbles. The expression of cytokines and adhesion molecules in the infarcted area of the myocardium was detected after three sessions of UTMD in 1 wk. Real-time quantitative reverse transcription polymerase chain reaction (RTQ-PCR) showed that the expression of vascular cell adhesion molecule-1 (VCAM-1), stromal cell-derived factor-1 (SDF-1) and vascular endothelial growth factor (VEGF) in the 1.5 W/cm(2) and 1 W/cm(2) groups was markedly increased compared with the 0.5 W/cm(2) or the control groups (3.8- to 4.7-fold, p

Whether ZES can further improve angiographic and clinical outcomes compared to SES still remains uncertain.The aim of this study was to assess the efficacy and safety of zotarolimus-eluting stents (ZES) compared with sirolimus-eluting stents (SES) in patients undergoing percutaneous coronary interventions (PCI).Major electronic information sources were explored for randomized controlled trials comparing ZES with SES among patients undergoing PCI during at least 9 months follow-up. The primary efficacy outcomes were target lesion revascularization (TLR), target vessel revascularization (TVR), and major adverse cardiac events (MACE); safety outcomes were stent thrombosis (ST), myocardial infarction (MI), and cardiac death.Seven comparative studies were identified (a total of 5983 patients). When compared with ZES at 12-month follow-up, SES significantly reduced risk of MACE (relative risk [RR]: 0.74, 95% confidence interval [CI]: 0.61 to 0.89, p=0.002), and TLR (RR:0.39; 95% CI: 0.29 to 0.52; p0.00001), without significant differences in terms of TVR (RR:0.68, 95% CI: 0.38 to 1.20; p=0.18), ST (RR:0.71; 95% CI: 0.39 to 1.31; p=0.28), cardiac death (RR:0.83; 95% CI: 0.49-1.42, p=0.50) or MI (RR:1.08; 95%CI: 0.80 to 1.45; p=0.62).At 12-month follow-up, SES are superior to ZES in reducing the incidences of TLR and MACE in patients undergoing PCI, without significant differences in terms of TVR, ST, cardiac death, and MI.

Objective Current literature shows there is widespread controversy regarding the indications and outcomes of using an intra-aortic balloon pump (IABP); furthermore, little is known about the late effects of IABP use. Design To determine whether IABP use can have beneficial effects for patients undergoing high risk reperfusion therapies, by conducting a meta-analysis of randomised trials. Setting Databases of Pubmed, Cochrane Library, and Clinicaltrials.gov were searched up to 15 June 2013. Patients Patients undergoing high risk reperfusion therapies. Interventions Randomised clinical trials comparing IABP with no IABP were considered eligible for this meta-analysis. Main outcome measures Primary outcomes were early (30-day) and long term (≥6-month) mortality. Results Among the 1079 articles retrieved, 10 randomised studies with 2037 high risk patients were included in the quantitative analysis. Meta-analysis revealed that early mortality rate did not differ between the IABP group and the non-IABP group (OR 0.79, 95% CI 0.48 to 1.29). However, long term mortality was significantly reduced in the IABP group (OR 0.63, 95% CI 0.45 to 0.9), and this effect seemed more pronounced in the subset of patients treated with contemporary percutaneous coronary intervention (OR 0.55, 95% CI 0.38 to 0.80). Further analysis found that IABP use was associated with a reduced risk of 30-day re-ischaemia rate (OR 0.62, 95% CI 0.42 to 0.91) and the composite outcome of re-ischaemia and heart failure events (OR 0.75, 95% CI 0.58 to 0.98). No significant heterogeneity was observed. Conclusions This meta-analysis suggests that adjunctive IABP use in high risk reperfusion therapy can improve long term survival.