Additional Lesion Sets in Ablation of Outflow Tract Premature Ventricular Contractions: A Randomized Clinical Trial.

Importance: Recurrence remains a challenge after ablation of outflow tract premature ventricular contractions (OT-PVCs). Although adding additional lesions next to the index effective ablation site is sometimes performed to reinforce the ablation, it remains uncertain whether this approach is effective. Objective: To test the hypothesis that additional ablation lesions would reduce the recurrence rate compared with single-point ablation at the index effective site for the ablation of OT-PVCs. Design, Setting, and Participants: This study was a multicenter, prospective, randomized clinical trial. Patients receiving their first catheter ablation for OT-PVCs were enrolled from 18 hospitals in China between October 2021 and February 2023. Scheduled follow-up duration was 3 months after the procedure. Intervention: After identifying the target point and eliminating the PVC by a single-point ablation, patients were randomized 1:1 into an additional ablation group or a control group. Main Outcomes and Measures: The primary end point of the study was freedom from PVC recurrence (≥80% reduction of PVC burden, which is the number of PVCs in 24 hours/total heartbeats in 24 hours × 100%) from baseline to 3 months postprocedure. Results: Of 308 patients enrolled in the study, 286 (mean [SD] age, 49.2 [14.6] years; 173 female [60.5%]) were randomized to the additional ablation or the control group. The additional ablation group had a mean (SD) of 6.3 (1.1) radiofrequency applications, whereas the control group (single-point ablation group) had a mean (SD) of 1 (0) radiofrequency application. After a median (IQR) follow-up of 3.2 (0) months, the rate of freedom from PVCs was significantly higher in the additional ablation group (139 of 142 [97.9%]) compared with the control group (115 of 139 [82.7%]; P < .001). Patients in the additional ablation group also had a more substantial reduction in PVC burden than the control group (mean [SD] reduction, 23.0% [10.5%] vs 19.0% [10.4%]; P = .002). There were no severe periprocedural complications in either group. Conclusions and Relevance: This randomized clinical trial showed a benefit of additional ablation in reducing the recurrence of OT-PVCs compared with the single-point ablation strategy, without increased complication risk. Additional ablations surrounding the index effective ablation point should be considered in OT-PVC ablation. Trial Registration: Chinese Clinical Trials Registry Identifier: ChiCTR2200055340.

Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.

BACKGROUND: Reportedly, the stress-hyperglycemia ratio (SHR) is closely associated with poor prognosis in patients with severe acute disease. However, the community-dwelling may also be in a state of stress due to environmental exposure. Our study aimed to explore the association between SHR and all-cause mortality in the community-dwelling population. METHODS: A total of 18 480 participants were included out of 82 091 from the NHANES 1999-2014 survey. The Kaplan-Meier survival analyses were used to assess the disparities in survival rates based on SHR, and the log-rank test was employed to investigate the distinctions between groups. The multivariate Cox regression analysis and restricted cubic spline (RCS) analysis were performed to assess the association of SHR with all-cause mortality. A subgroup analysis was also conducted. RESULTS: A total of 3188 deaths occurred during a median follow-up period of 11.0 (7.7; 15.4) years. The highest risk for all-cause mortality was observed when SHR≤ 0.843 or SHR ≥0.986 (log-rank p < .001). After adjusting for the confounding factors, compared with subjects in the second SHR quartile (Q2), participants in the highest (Q4, adjusted hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.28-1.73) and lowest quartiles (Q1, adjusted HR 1.37, 95% CI 1.16-1.60) have a higher probability of all-cause death. The RCS observed a dose-response U-shaped association between SHR and all-cause mortality. The U-shaped association between SHR and all-cause mortality was similar across subgroup analysis. CONCLUSIONS: The SHR was significantly associated with all-cause mortality in the community-dwelling population, and the relationship was U-shaped.

Optogenetic Stimulation of the Cardiac Vagus Nerve to Promote Heart Regenerative Repair after Myocardial Infarction.

Background: It had been shown that selective cardiac vagal activation holds great potential for heart regeneration. Optogenetics has clinical translation potential as a novel means of modulating targeted neurons. This study aimed to investigate whether cardiac vagal activation via optogenetics could improve heart regenerative repair after myocardial infarction (MI) and to identify the underlying mechanism. Methods: We used an adeno-associated virus (AAV) as the vector to deliver ChR2, a light-sensitive protein, to the left nodose ganglion (LNG). To assess the effects of the cardiac vagus nerve on cardiomyocyte (CM) proliferation and myocardial regeneration in vivo, the light-emitting diode illumination (470 nm) was applied for optogenetic stimulation to perform the gain-of-function experiment and the vagotomy was used as a loss-of-function assay. Finally, sequencing data and molecular biology experiments were analyzed to determine the possible mechanisms by which the cardiac vagus nerve affects myocardial regenerative repair after MI. Results: Absence of cardiac surface vagus nerve after MI was more common in adult hearts with low proliferative capacity, causing a poor prognosis. Gain- and loss-of-function experiments further demonstrated that optogenetic stimulation of the cardiac vagus nerve positively regulated cardiomyocyte (CM) proliferation and myocardial regeneration in vivo. More importantly, optogenetic stimulation attenuated ventricular remodeling and improved cardiac function after MI. Further analysis of sequencing results and flow cytometry revealed that cardiac vagal stimulation activated the IL-10/STAT3 pathway and promoted the polarization of cardiac macrophages to the M2 type, resulting in beneficial cardiac regenerative repair after MI. Conclusions: Targeting the cardiac vagus nerve by optogenetic stimulation induced macrophage M2 polarization by activating the IL-10/STAT3 signaling pathway, which obviously optimized the regenerative microenvironment and then improved cardiac function after MI.

Genetic association of lipid-lowering drugs with aortic aneurysms: a Mendelian randomization study.

AIMS: The lack of effective pharmacotherapies for aortic aneurysms (AA) is a persistent clinical challenge. Lipid metabolism plays an essential role in AA. However, the impact of lipid-lowering drugs on AA remains controversial. The study aimed to investigate the genetic association between lipid-lowering drugs and AA. METHODS AND RESULTS: Our research used publicly available data on genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) studies. Genetic instruments, specifically eQTLs related to drug-target genes and SNPs (single nucleotide polymorphisms) located near or within the drug-target loci associated with low-density lipoprotein cholesterol (LDL-C), have been served as proxies for lipid-lowering medications. Drug-Target Mendelian Randomization (MR) study is used to determine the causal association between lipid-lowering drugs and different types of AA. The MR analysis revealed that higher expression of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase) was associated with increased risk of AA (OR = 1.58, 95% CI = 1.20-2.09, P = 1.20 × 10-03) and larger lumen size (aortic maximum area: OR = 1.28, 95% CI = 1.13-1.46, P = 1.48 × 10-04; aortic minimum area: OR = 1.26, 95% CI = 1.21-1.42, P = 1.78 × 10-04). PCSK9 (proprotein convertase subtilisin/kexin type 9) and CETP (cholesteryl ester transfer protein) show a suggestive relationship with AA (PCSK9: OR = 1.34, 95% CI = 1.10-1.63, P = 3.07 × 10-03; CETP: OR = 1.38, 95% CI = 1.06-1.80, P = 1.47 × 10-02). No evidence to support genetically mediated NPC1L1 (Niemann-Pick C1-Like 1) and LDLR (low-density lipoprotein cholesterol receptor) are associated with AA. CONCLUSION: This study provides causal evidence for the genetic association between lipid-lowering drugs and AA. Higher gene expression of HMGCR, PCSK9, and CETP increases AA risk. Furthermore, HMGCR inhibitors may link with smaller aortic lumen size.

KEY FINDINGS: High expression of HMGCR, PCSK9, and CETP was positively correlated with the risk of aortic aneurysms, highlighting that the corresponding lipid-lowering drugs may be preferred for preventing arterial aneurysms in high-risk individuals with dyslipidemia. We found that genetically predicted HMGCR inhibitors were positively associated with smaller aortic lumen size, which is the first time to support the causal association of gene HMGCR on the lumen size of aortic aneurysms.

This Mendelian randomization study used publicly available data involving over 1 million individuals to demonstrate the causal relationship between five target genes of LDL-C-lowering medicines and the risk of aortic aneurysms, and implied one lipid-lowering drug may link with the lumen size of aortic aneurysms.

Tricuspid isthmus ablation with pulsed-field power by linear catheter: a case report.

Background: Pulsed-field ablation using annular or petal-shaped catheters had been proven to be effective for achieving electrical isolation of pulmonary veins in patients with atrial fibrillation. However, the utilization of linear pulse-field power for treating atrial flutter has yet to been documented. Case summary: In this report, we present a case involving the successful treatment of tricuspid isthmus-dependent atrial flutter treated with a linear pulsed-field catheter. The patient, a 71-year-old male, presents with an electrocardiogram indicating atrial flutter. Subsequent electrophysiological examination reveals typical atrial flutter that is dependent on the cavo-tricuspid isthmus (CTI). This condition is successfully terminated through the application of linear pulsed-field ablation. Discussion: This case represents a pioneering instance of CTI-dependent atrial flutter ablation utilizing linear pulse-field power. The innovative approach not only effectively treats the patient but also serves as a valuable reference for future applications of linear treatment with pulsed-field ablation.

Comparisons of procedural characteristics and clinical outcomes between SMARTTOUCH SURROUNDFLOW catheter and other catheters for atrial fibrillation radiofrequency catheter ablation: a systematic literature review.

BACKGROUND: SMARTTOUCH SURROUNDFLOW (STSF) catheter is the new generation of SMARTTOUCH (ST) catheter with an upgraded irrigation system for radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF). METHODS: This systematic literature review searched the major English and Chinese bibliographic databases from 2016 to 2022 for any original clinical studies assessing the STSF catheter for RFCA in AF patients. Meta-analysis with a random effects model was used for evidence synthesis. RESULTS: Pooled outcomes from 19 included studies indicated that STSF catheter was associated with a significantly shorter procedure time (weighted mean difference (WMD): -17.4 min, p<0.001), shorter ablation time (WMD: -6.6 min, p<0.001) and lower catheter irrigation fluid volume (WMD: -492.7 mL, p<0.001) than ST catheter. Pooled outcomes from four included studies with paroxysmal AF patients reported that using the STSF catheter for RFCA was associated with a significantly shorter ablation time (WMD: -5.7 min, p<0.001) and a lower risk of 1-year postablation arrhythmia recurrence (rate ratio: 0.504, p<0.001) than the SURROUNDFLOW (SF) catheter. Significant reductions in procedure time and ablation time associated with the STSF catheter were also reported in the other four studies using non-ST/SF catheters as the control. Overall complications of STSF catheter and control catheters were comparable. CONCLUSIONS: Using the STSF catheter was superior to using the ST catheter to conduct RFCA for AF by significantly reducing procedure time, ablation time, fluoroscopy time and irrigation fluid volume. The superiority of the STSF catheter over the SF catheter and other non-ST/SF catheters for RFCA needs further confirmation.

Prognostic impact of malnutrition in patients with coronary artery disease: a systematic review and meta-analysis.

CONTEXT: Conflicting predictions of malnutrition for the long-term prognosis of coronary artery disease (CAD) exist. OBJECTIVE: This study aimed to investigate the relationship between malnutrition and long-term prognosis of patients with CAD. DATA SOURCES: Four databases were searched for articles from February 11, 1936, to September 10, 2022. DATA EXTRACTION: Cohort studies adjusting for multiple cardiovascular risk factors with data on CAD and malnutrition were included. Malnutrition was measured and defined by different nutritional evaluation tools. The hazard ratios (HRs) and confidence intervals (CIs) for all-cause mortality and major adverse cardiovascular events (MACEs) were synthesized. Subgroup analyses were performed based on study design, assessment tools, ethnicity/race, follow-up, sample size, and types of CAD. Meta-regression was used to compare whether the effect sizes of the 2 subgroups were statistically significant. DATA ANALYSIS: A total of 30 cohort studies were included, totaling 81 361 participants with CAD. Nutritional evaluation tools, including the Geriatric Nutritional Risk Index (GNRI), Controlling Nutritional Status (CONUT), Nutritional Risk Screening 2002, Mini-Nutritional Assessment, and Prognostic Nutritional Index, were used. Malnutrition increased all-cause mortality (HR = 1.72; 95% CI: 1.53, 1.93) and MACEs (HR = 1.47; 95% CI: 1.35, 1.60) in patients with CAD. Subgroup analysis revealed the results were consistent across study design, ethnicity/race, follow-up, sample size, and types of CAD. Subgroup analyses and meta-regression revealed that malnutrition was associated with a higher risk of all-cause mortality (HR = 2.26; 95% CI: 1.91, 2.68) and MACEs (HR = 2.28; 95% CI: 1.69, 3.08) in patients with stable CAD than those with other types of CAD. Meta-regression revealed that the GNRI (HR = 2.20; 95% CI: 1.65, 2.93) was more effective than CONUT (HR = 1.47; 95% CI: 1.21, 1.78) in predicting all-cause mortality. CONCLUSION: Malnutrition independently increased all-cause mortality by 72% and MACEs by 47% in patients with CAD, especially with stable CAD. The GNRI is a more effective nutritional evaluation tool than CONUT in predicting all-cause mortality.

Cumulative remnant cholesterol predicts cardiovascular outcomes in elderly patients with atherosclerotic cardiovascular disease.

AIMS: Remnant cholesterol (RC) reportedly mediates residual cardiovascular risk in atherosclerotic cardiovascular diseases (ASCVD). However, few studies have characterized long-term cumulative RC exposure among elderly people. The study aimed to evaluate the association between cumulative exposure to RC and incident major adverse cardiovascular events (MACE) by analysing a cohort of elderly patients with ASCVD. METHODS AND RESULTS: This retrospective multicentre cohort study enrolled ASCVD participants aged ≥75 years with baseline visits occurring from 2006 to 2012 followed by four in-person visits. Cumulative RC was estimated as the area under the curve using measurements from the first to fourth visits by using 9-year data. The time-weighted average (TWA) RC was expressed as cumulative exposure to RC averaged by years. All outcomes were follow-up from the fourth visit to the year 2021. Outcomes included a composite of MACE (stroke, unstable angina pectoris, myocardial infarction, and cardiac death). We included 4,680 participants (73.1% male, mean age 79.3 ± 2.5 years). The median follow-up duration was 6.1 years (interquartile range: 3.4-6.6 years). In the multivariable model adjusted for traditional cardiovascular risk factors, low-density lipoprotein cholesterol level, and most recent RC level, the hazard ratios for MACE that compared the high and low tertiles of the RC variables were 1.30 [95% confidence interval (CI), 1.16-1.44] for cumulative RC and 1.36 (95% CI, 1.23-1.52) for TWA RC. Consistent significant associations were observed among most propensity score analyses. CONCLUSIONS: Long-term cumulative RC was independently associated with incident MACE in elderly participants with ASCVD, suggesting that achieving and maintaining optimal RC levels later in life may still improve cardiovascular outcomes.

This retrospective multicentre cohort study, enrolling 4680 participants aged ≥75 years with pre-existing atherosclerotic cardiovascular diseases (ASCVD), found that greater cumulative exposure to remnant cholesterol (RC) across a 9-year span was independently associated with an increased incidence of cardiovascular events, suggesting that cumulative RC may be a powerful predictor of cardiovascular outcomes in patients with ASCVD.

Chinese expert consensus on the construction of the fluoroless cardiac electrophysiology laboratory and related techniques.

Transcatheter radiofrequency ablation has been widely introduced for the treatment of tachyarrhythmias. The demand for catheter ablation continues to grow rapidly as the level of recommendation for catheter ablation. Traditional catheter ablation is performed under the guidance of X-rays. X-rays can help display the heart contour and catheter position, but the radiobiological effects caused by ionizing radiation and the occupational injuries worn caused by medical staff wearing heavy protective equipment cannot be ignored. Three-dimensional mapping system and intracardiac echocardiography can provide detailed anatomical and electrical information during cardiac electrophysiological study and ablation procedure, and can also greatly reduce or avoid the use of X-rays. In recent years, fluoroless catheter ablation technique has been well demonstrated for most arrhythmic diseases. Several centers have reported performing procedures in a purposefully designed fluoroless electrophysiology catheterization laboratory (EP Lab) without fixed digital subtraction angiography equipment. In view of the lack of relevant standardized configurations and operating procedures, this expert task force has written this consensus statement in combination with relevant research and experience from China and abroad, with the aim of providing guidance for hospitals (institutions) and physicians intending to build a fluoroless cardiac EP Lab, implement relevant technologies, promote the standardized construction of the fluoroless cardiac EP Lab.

Circumferential Pulmonary Vein Isolation With vs Without Additional Low-Voltage-Area Ablation in Older Patients With Paroxysmal Atrial Fibrillation: A Randomized Clinical Trial.

Importance: The overall success rate of circumferential pulmonary vein isolation (CPVI) treatment in patients with paroxysmal atrial fibrillation (AF) remains suboptimal, especially in older patients. Objective: To explore the incremental benefit of low-voltage-area ablation after CPVI in older patients with paroxysmal AF. Design, Setting, and Participants: This randomized clinical trial was an investigator-initiated trial to compare the efficacy of additional low-voltage-area ablation beyond CPVI vs CPVI alone in older patients with paroxysmal AF. Participants were patients aged 65 to 80 years with paroxysmal AF who were referred for catheter ablation. They were enrolled in 14 tertiary hospitals in China from April 1, 2018, to August 3, 2020, and follow-up occurred through August 15, 2021. Interventions: Patients were randomized (1:1) to undergo CPVI plus low-voltage-area ablation or CPVI alone. Low-voltage areas were defined as areas with amplitude less than 0.5 mV in more than 3 adjacent points. If low-voltage areas existed, additional substrate ablation was performed in the CPVI plus group but not the CPVI alone group. Main Outcomes and Measures: The primary end point of the study was freedom from atrial tachyarrhythmia as documented by electrocardiogram during a clinical visit or lasting longer than 30 seconds during Holter recordings occurring after a single ablation procedure. Results: Among 438 patients who were randomized (mean [SD] age, 70.5 [4.4] years; 219 men [50%]), 24 (5.5%) did not complete the blanking period and were not included for efficacy analysis. After a median follow-up of 23 months, the recurrence rate of atrial tachyarrhythmia was significantly lower in the CPVI plus group (31/209 patients, 15%) compared with the CPVI alone group (49/205, 24%; hazard ratio [HR], 0.61; 95% CI, 0.38-0.95; P = .03). In subgroup analyses, among all patients with low-voltage area, CPVI plus substrate modification was associated with a 51% decreased risk of ATA recurrence compared with CPVI alone (HR, 0.49; 95% CI, 0.25-0.94; P = .03). Conclusions and Relevance: This study found that additional low-voltage-area ablation beyond CPVI decreased the ATA recurrence in older patients with paroxysmal AF compared with CPVI alone. Our findings merit further replication by larger trials with longer follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT03462628.

Half versus normal saline irrigation during catheter ablation of outflow tract ventricular arrhythmias (HALF): a multi-center, parallel, open-label, randomized controlled study.

BACKGROUND: Animal studies demonstrated that deeper lesions could be achieved during radio-frequency catheter ablation (RFCA) by using half saline (HS) compared to normal saline (NS) as irrigation. OBJECTIVES: This study sought to compare the efficiency and safety of HS and NS for irrigation during RFCA of idiopathic outflow tract ventricular arrhythmia (OT-VA). METHODS: In this multicenter, randomized controlled study, 167 patients undergoing RFCA of OT-VA were randomized 1:1 to receive HS- or NS-irrigated ablation. Acute success was defined as the absence of induced targeted premature ventricular contraction (PVC) at the end of the procedure. The 6-month success was defined as a ≥ 80% reduction of pre-procedural PVC burden. RESULTS: There were no differences of baseline characteristics between the HS and NS group. Patients in HS group had shorter total ablation time (259.5 ± 155.5 S vs. 355.6 ± 230.7 S, P = 0.04) than that in NS group. The acute and 6-month success rates were similar between the HS and NS group (92.8 vs. 91.7%, P = 0.79; 90.9 vs. 92.1%, P = 0.79, respectively). No significant difference was observed in the incidence of steam pops between the HS and NS group (2.4 vs. 1.2%, P = 0.62). CONCLUSIONS: The ablation using HS irrigation achieved similar success rate and safety compared to that using NS irrigation but was associated with a shorter total ablation time. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200059205).

Low-Intensity Focused Ultrasound Ameliorates Ischemic Heart Failure Related to the Cholinergic Anti-Inflammatory Pathway.

OBJECTIVES: This study aims to determine the effect of low-intensity focused ultrasound (LIFU) in ischemic heart failure (IHF) and explore the potential neuroimmune mechanism. METHODS: Sprague-Dawley rats were subjected to ultrasound (US) with specific parameters, and electrocardiograms were recorded to analyze the effect of LIFU and/or vagal denervation on heart rate. Thereafter, myocardial infarction (MI) was induced by left anterior artery ligation, and LIFU was performed three times a day for 25 days after MI. Echocardiography, Masson staining, and ELISA were used to evaluate the effect of LIFU on the structure and function of the heart. Finally, ELISA, flow cytometry, qRT-PCR, and Western blot analysis were performed to determine the effect of LIFU on the inflammation and the expression of the cholinergic anti-inflammatory pathway (CAP)-related mediators. RESULTS: LIFU reduced heart rate in rats (control vs LIFU, P < .01), and vagotomy (VT) eliminated this effect of LIFU on heart rate (VT vs LIFU + VT, P > .01). LIFU-ameliorated IHF in terms of cardiac structure and function (MI vs MI + LIFU, P < .01), but VT abrogated the beneficial effect of LIFU (MI + VT vs MI + LIFU + VT, P > .01). After the treatment of LIFU, decreased levels of inflammatory cytokines, increased proportion of anti-inflammatory macrophages, and increased expression of CAP-related mediators (MI vs MI + LIFU, P < .01). CONCLUSIONS: LIFU ameliorates IHF whereas the CAP plays a promising role. LIFU has the potential to be a novel nonpharmacological and noninvasive therapy for the treatment of coronary artery disease and other cardiovascular diseases.

A novel and effective ECG method to differentiate right from left ventricular outflow tract arrhythmias: Angle-corrected V2S.

Background and aims: Standard 12-lead electrocardiogram (ECG) patterns combined with the anatomical cardiac long-axis angle revealed by chest X-ray can prevent the influence of cardiac rotation, physical shape, and lead position, so it may be an ideal means to predict the origin of the outflow tract (OT) ventricular arrhythmias (OTVAs) for ablation procedures. The study explores the value of this strategy in identifying the origin of OTVA. Methods: This study was conducted using a retrospective cohort and a prospective cohort of consecutive patients at two centers. The anatomical cardiac long-axis angle was calculated by measuring the angle between the cardiac long-axis (a line joining the apex to the midpoint of the mitral annulus) and the horizontal plane on a chest X-ray. The V2S angle was calculated as the V2S amplitude times the angle. We ultimately enrolled 147 patients with symptomatic OTVAs who underwent successful radiofrequency catheter ablation (RFCA) (98 women (66.7%); mean age 46.9 ± 14.7 years; 126 right ventricular OT (RVOT) origins, 21 left ventricular OT (LVOT) origins) as a development cohort. The new algorithm was validated in 48 prospective patients (12 men (25.0%); mean age 48.0 ± 15.8 years; 36 RVOT, 12 LVOT origins). Results: Patients with RVOT VAs had greater V2S, long-axis angle, and V2S angle than patients with LVOT VA (all P < 0.001). The cut-off V2S angle obtained by receiver operating characteristic (ROC) curve analysis was 58.28 mV° for the prediction of RVOT origin (sensitivity: 85.7%; specificity: 95.2%; positive predictive value: 99.1%; negative predictive value: 52.6%). The AUC achieved using the V2S angle was 0.888 (P < 0.001), which was the highest among all indexes (V2S/V3R: 0.887 (P < 0.016); TZ index: 0.858 (P < 0.001); V1-2 SRd: 0.876 (P < 0.001); V3 transition: 0.651 (P < 0.001)). In the prospective cohort, the V2S angle had a high overall accuracy of 93.8% and decreased the procedure time (P = 0.002). Conclusion: V2S angle can be a novel measure that can be used to accurately differentiate RVOT from LVOT origins. It could help decrease ablation duration and radiation exposure.

Sono-assisted-thrombolysis by three-dimensional diagnostic ultrasound improves epicardial recanalization and microvascular perfusion in acute myocardial infarction.

Background: This study aimed to evaluate the multiple interactions between therapeutic ultrasound (TUS), microbubbles (MB), and recombinant tissue plasminogen activator (r-tPA) by using three-dimensional (3D) ultrasound to examine the impact of thrombolysis with r-tPA on epicardial recanalization and microcirculation in patients with acute ST-segment-elevation myocardial infarction (STEMI). Methods: Acute thrombotic occlusion of the left anterior descending (LAD) artery was induced in 32 Bama pigs, who were fed a high-cholesterol diet and randomized into four groups: (I) a 3D-sono-assisted-thrombolysis (3D/TUS + MB + r-tPA) group; (II) a 3D/TUS + MB group; (III) a full-dose r-tPA group; and (IV) a 3D/TUS alone group. Epicardial angiographic recanalization rate, microcirculation in the at-risk myocardium, ST-segment elevation on electrocardiogram, and changes in the at-risk myocardium and the myocardial infarct area were compared between the groups. Results: After treatment, distal LAD recanalization was observed in 87.5% (7/8) of pigs in the 3D/TUS + MB + r-tPA group, which was significantly higher than the rates observed in the 3D/TUS + MB (37.5%) and the full-dose r-tPA (50.0%) groups (all P<0.05). The average acoustic intensity in the 3D/TUS + MB + r-tPA group (193.78±10.15 dB) was also significantly higher than that in the 3D/TUS + MB (154.29±31.94 dB) and the r-tPA (141.42±28.31 dB) groups (all P<0.05). The decrease in ST-segment elevation in the 3D/TUS + MB + r-tPA group (1.31±1.22 mm) was significantly higher than that in the 3D/TUS + MB (5.38±1.77 mm) and the r-tPA (4.30±2.08 mm) groups (all P<0.05). Furthermore, the ratio of the infarcted myocardial area divided by the at-risk myocardial area was markedly lower in the 3D/TUS + MB + r-tPA group (0.51±0.14) than in the 3D/TUS + MB (0.69±0.28) and r-tPA (0.75±0.23) groups (all P<0.05). Conclusions: Three-dimensional sono-assisted-thrombolysis directly improves infarct-related recanalization rates, enhances microcirculation, reduces r-tPA dosage, and ameliorates the thrombolytic effect of r-tPA in acute STEMI.

Dapagliflozin attenuates residual cardiac remodeling after surgical ventricular reconstruction in mice with an enlarged heart after myocardial infarction.

BACKGROUND: Severe heart failure refractory to conventional therapy requires alternative treatment modalities. Surgical ventricular reconstruction (SVR) has been used to reverse cardiac remodeling in post-myocardial infarction (MI) patients with large left ventricular (LV) aneurysm, however, residual LV remodeling and dysfunction remain postoperatively. It is unclear whether SVR recovers response to drug treatment and whether the sodium-glucose co-transporter 2 inhibitor dapagliflozin (DAPA) reverses residual LV remodeling after SVR. METHODS: Adult male C57 mice were subjected to MI or sham surgery. Four-week later, MI mice with LV aneurysm underwent modified SVR or second open-chest sham operation and were randomized to DAPA or vehicle for four-week. Cardiac remodeling, LV function, and the underlying mechanisms were evaluated by echocardiography, invasive LV hemodynamic measurements, mRNA sequencing, and bioinformatics analysis. RESULTS: SVR significantly decreased LV volume; increased myocardial strain, LV pressure change rates and end-systolic elastance; and decreased heart-to-body weight ratio and myocardial fibrosis. However, significant residual cardiac remodeling remained. DAPA significantly attenuated residual cardiac remodeling and improved LV function in SVR mice but did not have curative effects in non-SVR mice. Of the 1532 genes differentially expressed in SVR and MI mice, 1037 were associated with cardiac metabolism; Src, Crebbp, Fn1, Grb2, and Mapk14 were the top 5 hub genes. Unlike sham surgery, MI upregulated those 5 genes, and treatment with SVR + DAPA normalized their expression. CONCLUSIONS: SVR restores therapeutic response in the post-MI heart with large LV aneurysm, and DAPA attenuates residual cardiac remodeling after SVR by normalizing some cardiac metabolism-related hub genes.

Efficacy of ablation index-guided pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Ablation index (AI) is a novel technology of ablation lesion quality to help improve homogeneity of lesion size and continuity. In this study, we aim to evaluate whether AI-guided PVI improves clinical outcomes compared to CF-guided PVI in patients with paroxysmal AF (PAF). METHODS: Patients undergoing first-time radiofrequency ablation for PAF were randomized in a 2:1 ratio to two groups: AI-guided PVI and CF-guided PVI. In the AI group, AI ≥500 was recommended at the anterior/superior/inferior walls, 350-400 at the posterior wall, and inter-lesion distance ≤4 mm. The primary endpoint is the freedom from atrial arrhythmia recurrence during 12 months follow-up, without antiarrhythmic drug therapy (ADT). The key secondary endpoints include intra-procedural efficiency and peri-procedural complications. RESULTS: Two hundred twenty five patients were randomized (AI group [n = 149] and CF group [n = 76]). First-pass isolation rate in AI group was significantly higher than that in CF group (58.3% vs. 43.4%, p = .035). After a median follow-up of 12.2 months, 154/225 (68.4%) of patients were free from atrial arrhythmia recurrence without ADT, which was higher in AI group compared with CF group, but without significant difference (71.1% vs. 63.2%, p = .253). The incidence of peri-procedural complications is low and without difference between two groups. CONCLUSIONS: AI-guided ablation provided higher acute efficacy than CF-guided ablation in PV isolation for patients with paroxysmal AF. The long-term success rate in AI group was higher than CF group, but did not reach statistical significance.

Rationale and study design for empirical additional lesions for premature ventricular complex from the outflow tract: a multi-center, prospective randomized trial (EASE-PVC study).

BACKGROUND: Late recurrence after ablation remains a significant issue in patients with premature ventricular complexes (PVCs) who undergo catheter ablation. In this study, we aimed to test the hypothesis that empirical additional ablation (EAA) would improve the long-term control of PVCs from outflow tracts (OT-PVCs) compared with the approach of limited single point ablation at the assumptive location. METHODS: EASE-PVC study (ChiCTR2200055340) is a prospective multi-center, randomized, and controlled trial designed to assess the effectiveness and safety of empirical additional ablation in patients with OT-PVCs. After successful elimination of OT-PVCs, the patients will be randomized into two groups. In patients randomized to the EAA group, additional lesion applications at sites surrounding the successful ablation site will be delivered empirically. For patients randomized to the control group, no additional empiric ablation will be performed around the successful ablation site. The primary endpoint will be freedom from PVC recurrence at 3 months following ablation, without antiarrhythmic drug therapy. CONCLUSIONS: The EASE-PVC study is designed to compare the effectiveness and safety of two different strategies for ablation in patients with OT-PVCs, namely empirical additional ablation strategy versus conventional single point ablation strategy. This prospective, multi-center, and randomized controlled trial, with comparative data evaluating procedural and long-term follow-up results, aims to elucidate the superiority of empirical additional ablation for the long-term control of OT-PVCs compared with the traditional single point ablation strategy. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trials Registry Identifier: ChiCTR2200055340.

Gut Microbiota and Metabolites in Atrial Fibrillation Patients and Their Changes after Catheter Ablation.

The gut microbiota has been shown to be associated with multiple cardiovascular diseases, but there is little research on the gut microbiota and atrial fibrillation (AF); thus, how the gut microbiota and metabolites change in AF patients after catheter ablation is unclear. In this study, we used 16S rRNA high-throughput sequencing and nontargeted metabolomic detection to conduct horizontal and longitudinal analyses of the gut microbiota and metabolites of AF patients. Compared with a control group, species richness and diversity increased significantly in AF patients. Among them, opportunistic pathogenic bacteria, such as Klebsiella, Haemophilus, Streptococcus, and Enterococcus, were significantly increased, and symbiotic bacteria, such as Agathobacter and Butyrivibrio, were significantly reduced. After catheter ablation, intestinal symbiotic bacteria (Lactobacillus, Agathobacter, Lachnospira, etc.) were increased in most AF patients, while pathogenic bacteria (Ruminococcus, etc.) were reduced. Moreover, in AF patients, caffeine, which was negatively correlated with Klebsiella, was downregulated, and estradiol and ascorbic acid, which were positively correlated with Agathobacter, were also downregulated. After catheter ablation, citrulline, which was positively correlated with Ralstonia and Lactobacillus, was increased. Oleanolic acid, which was negatively correlated with Ralstonia was downregulated. In conclusion, our results not only show overall changes in the gut microbiota and metabolites in AF patients but also indicate their changes in the short term after catheter ablation. These data will provide novel possibilities for the future clinical diagnosis and treatment of AF. IMPORTANCE Gut microbiota and metabolites play a very important role in human health and can not only assess human health but also treat and prevent diseases. We analyzed the characteristics of the microbiota and metabolites in the human gut and found the effect of disease on gut microbiota and metabolites, which may be of important value in the pathogenesis of atrial fibrillation. At the same time, we also observed dynamic changes in gut microbiota and metabolites with the intervention of catheter ablation, which was not available in previous studies.

An electrographic AV optimization for the maximum integrative atrioventricular and ventricular resynchronization in CRT.

BACKGROUND: Atrioventricular (AV) delay could affect AV and ventricular synchrony in cardiac resynchronization therapy (CRT). Strategies to optimize AV delay according to optimal AV synchrony (AVopt-AV) or ventricular synchrony (AVopt-V) would potentially be discordant. This study aimed to explore a new AV delay optimization algorithm guided by electrograms to obtain the maximum integrative effects of AV and ventricular resynchronization (opt-AV). METHODS: Forty-nine patients with CRT were enrolled. AVopt-AV was measured through the Ritter method. AVopt-V was obtained by yielding the narrowest QRS. The opt-AV was considered to be AVopt-AV or AVopt-V when their difference was < 20 ms, and to be the AV delay with the maximal aortic velocity-time integral between AVopt-AV and AVopt-V when their difference was > 20 ms. RESULTS: The results showed that sensing/pacing AVopt-AV (SAVopt-AV/PAVopt-AV) were correlated with atrial activation time (Pend-As/Pend-Ap) (P < 0.05). Sensing/pacing AVopt-V (SAVopt-V/PAVopt-V) was correlated with the intrinsic AV conduction time (As-Vs/Ap-Vs) (P < 0.01). The percentages of patients with more than 20 ms differences between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were 62.9% and 57.1%, respectively. Among them, opt-AV was linearly correlated with SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The sensing opt-AV (opt-SAV) = 0.1 × SAVopt-AV + 0.4 × SAVopt-V + 70 ms (R2 = 0.665, P < 0.01) and the pacing opt-AV (opt-PAV) = 0.25 × PAVopt-AV + 0.5 × PAVopt-V + 30 ms (R2 = 0.560, P < 0.01). CONCLUSION: The SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V were correlated with the atrial activation time and the intrinsic AV conduction interval respectively. Almost half of the patients had a > 20 ms difference between SAVopt-AV/PAVopt-AV and SAVopt-V/PAVopt-V. The opt-AV could be estimated based on electrogram parameters.

Excessive fibroblast growth factor 23 promotes renal fibrosis in mice with type 2 cardiorenal syndrome.

Cardiorenal syndrome (CRS) has a high mortality, but its pathogenesis remains elusive. Fibroblast growth factor 23 (FGF23) is increased in both renal dysfunction and cardiac dysfunction, and FGF receptor 4 (FGFR4) has been identified as a receptor for FGF23. Deficiency of FGF23 causes growth retardation and shortens the lifespan, but it is unclear whether excess FGF23 is detrimental in CRS. This study sought to investigate whether FGF23 plays an important role in CRS-induced renal fibrosis. A mouse model of CRS was created by surgical myocardial infarction for 12 weeks. CRS mice showed a significant increase of circulatory and renal FGF23 protein levels, as well as an upregulation of p-GSK, active-ß-catenin, TGF-ß, collagen I and vimentin, a downregulation of renal Klotho expression and induction of cardiorenal dysfunction and cardiorenal fibrosis. These changes were enhanced by cardiac overexpression of FGF23 and attenuated by FGF receptor blocker PD173074 or ß-catenin blocker IGC001. In fibroblasts (NRK-49F), expression of FGFR4 rather than Klotho was detected. Recombinant FGF23 upregulated the expression of p-GSK, active-ß-catenin, TGF-ß, collagen I and vimentin proteins. These changes were attenuated by FGFR4 blockade with BLU9931 or ß-catenin blockade with IGC001. We concluded that FGF23 promotes CRS-induced renal fibrosis mediated by partly activating FGFR4/ß-catenin signaling pathway.