Left atrial strain parameters to predicting elevated left atrial pressure in patients with atrial fibrillation.

OBJECTIVES: To assess the ability of left atrial (LA) strain parameters to discriminate patients with elevated left atrial pressure (LAP) from patients with atrial fibrillation (AF). METHODS AND RESULTS: A total of 142 patients with non-valvular AF who underwent first catheter ablation (CA) between November 2022 and November 2023 were enrolled in the study. Conventional and speckle-tracking echocardiography (STE) were performed in all patients within 24 h before CA, and LAP was invasively measured during the ablation procedure. According to mean LAP, the study population was classified into two groups of normal LAP (LAP < 15 mmHg, n = 101) and elevated LAP (LAP ≥ 15 mmHg, n = 41). Compared with the normal LAP group, elevated LAP group showed significantly reduced LA reservoir strain (LASr) [9.14 (7.97-11.80) vs. 20 (13.59-26.96), p < .001], and increased LA filling index [9.60 (7.15-12.20) vs. 3.72 (2.17-5.82), p < .001], LA stiffness index [1.13 (.82-1.46) vs. .47 (.30-.70), p < .001]. LASr, LA filling index and LA stiffness index were independent predictors of elevated LAP after adjusted by the type of AF, EDT, E/e', mitral E, and peak acceleration rate of mitral E velocity. The receiver-operating characteristic curve (ROC) analysis showed LA strain parameters (area under curve [AUC] .794-.819) could provide similar or greater diagnostic accuracy for elevated LAP, as compared to conventional echocardiographic parameters. Furthermore, the novel algorithms built by LASr, LA stiffness index, LA filling index, and left atrial emptying fraction (LAEF), was used to discriminate elevated LAP in AF with good accuracy (AUC .880, accuracy of 81.69%, sensitivity of 80.49%, and specificity of 82.18%), and much better than 2016 ASE/EACVI algorithms in AF. CONCLUSION: In patients with AF, LA strain parameters could be useful to predict elevated LAP and non-inferior to conventional echocardiographic parameters. Besides, the novel algorithm built by LA strain parameters combined with conventional parameters would improve the diagnostic efficiency.

Causal associations between type 1 diabetes mellitus and cardiovascular diseases: a Mendelian randomization study.

BACKGROUND: The presence of type 1 diabetes mellitus (T1DM) has been demonstrated to pose an increased risk for developing cardiovascular diseases (CVDs). However, the causal relationships between T1DM and CVDs remain unclear due to the uncontrolled confounding factors and reverse causation bias of the observational studies. METHODS: Summary statistics of T1DM and seven CVDs from the largest available genome-wide association studies (GWAS) of European ancestry and FinnGen biobank were extracted for the primary MR analysis, and the analysis was replicated using UK biobank (UKBB) for validation. Three complementary methods: inverse variance weighted (IVW), weighted median, and MR-Egger were used for the MR estimates. The potential pleiotropic effects were assessed by MR-Egger intercept and MR-PRESSO global test. Additionally, multivariable MR (MVMR) analysis was performed to examine whether T1DM has independent effects on CVDs with adjustment of potential confounding factors. Moreover, a two-step MR approach was used to assess the potential mediating effects of these factors on the causal effects between T1DM and CVDs. RESULTS: Causal effects of T1DM on peripheral atherosclerosis (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.02-1.10; p = 0.002)] and coronary atherosclerosis (OR = 1.03, 95% CI: 1.01-1.05; p = 0.001) were found. The results were less likely to be biased by the horizontal pleiotropic effects (both p values of MR-Egger intercept and MR-PRESSO Global test > 0.05). In the following MVMR analysis, we found the causal effects of T1DM on peripheral atherosclerosis and coronary atherosclerosis remain significant after adjusting for a series of potential confounding factors. Moreover, we found that hypertension partly mediated the causal effects of T1DM on peripheral atherosclerosis (proportion of mediation effect in total effect: 11.47%, 95% CI: 3.23-19.71%) and coronary atherosclerosis (16.84%, 95% CI: 5.35-28.33%). We didn't find significant causal relationships between T1DM and other CVDs, including heart failure (HF), coronary artery disease (CAD), atrial fibrillation (AF), myocardial infarction (MI) and stroke. For the reverse MR from CVD to T1DM, no significant causal relationships were identified. CONCLUSION: This MR study provided evidence supporting the causal effect of T1DM on peripheral atherosclerosis and coronary atherosclerosis, with hypertension partly mediating this effect.

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.

LCZ696 Ameliorates Tachycardia-Induced Cardiac Calcium Dyshomeostasis in the SERCA2α-Dependent Pathway.

The incidence, prevalence, and economic burden of heart failure have continued to increase worldwide. It remains unclear whether LCZ696 can ameliorate calcium reuptake in the sarcoplasmic reticulum via the sarcoplasmic endoplasmic reticulum calcium ion-ATPase 2α (SERCA2α)-dependent pathway during cardiac diastole. We investigated whether LCZ696 could ameliorate tachycardia-induced myocardial injury by modulating cardiac SERCA2α levels. A tachycardia-induced myocardial injury model was established by daily intraperitoneal administration of 60 mg/kg isoprenaline (ISO) for 2 weeks. LCZ696 was orally administered for the following 4 weeks. SERCA2α and calcium ion (Ca2+)-related protein expression was assessed by quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting. For additional in vitro studies, HL-1 cardiomyocytes were used. A SERCA2α overexpression vector was constructed and transfected into HL-1 cells. The expression of SERCA2α and Ca2+-related proteins were also measured using qRT-PCR and western blotting. Our in vivo results demonstrated that myocardial injury was successfully induced by intraperitoneal administration of ISO. The expression of both SERCA2α- and Ca2+-related proteins was impaired. Oral administration of LCZ696 increased the expression of SERCA2α, alleviated Ca2+-related protein impairment and cardiac Ca2+ dyshomeostasis, and ameliorated myocardial injury. These results were compared with our in vitro findings. Ca2+-related proteins are affected by the overexpression of SERCA2α. LCZ696 improved tachycardia-induced myocardial injury by increasing SERCA2α expression, which reversed the development of heart failure in ISO-induced mice. These results provide new insights into how sustained LCZ696 treatment in heart failure improves cardiac function through intracellular Ca2+-regulatory mechanisms.

Heart acceleration and deceleration capacities associated with dilated cardiomyopathy.

BACKGROUND: Heart rate deceleration capacity and acceleration capacity are novel autonomic nervous system indicators of cardiac neural regulation. Dilated cardiomyopathy (DCM) changes cardiac electrophysiology; however, how deceleration capacity and acceleration capacity associated with DCM remain unclear. MATERIALS AND METHODS: To evaluate the association between heart rate acceleration capacity, deceleration capacity and DCM, 66 DCM patients with DCM and 209 controls were enrolled in the study. Demographic data, echocardiographic data, heart rate variability, deceleration capacity and acceleration capacity were collected. The association pattern between DCM and these indexes were studied by multiple logistic regression analysis. RESULTS: Deceleration capacity and acceleration capacity were independent risk factors for DCM with an odds ratio (OR) and 95% confidence interval (CI), determined by multiple logistic regression analysis, of 7·97 (3·87-16·42) and 0·09 (0·05-0·19), respectively. Univariate ordinal logistic regression analysis showed that acceleration capacity, fastest heart rate, standard deviation of normal-to-normal RR intervals (SDNN) and left ventricular ejection fraction (LEVF) associated with heart failure grade. The OR for each covariate was further adjusted for the effects of other significant covariates in multivariate ordinal logistic regression analysis. Acceleration capacity, fastest heart rate and LVEF were still independent risk factors in the final equation with ORs of 1·32 (1·03-1·79), 1·04 (0·01-1·07) and 0·46 (0·23-0·93), respectively. CONCLUSION: Heart rate acceleration capacity and deceleration capacity are independent risk factors for DCM, and acceleration capacity is a predictive factor for heart failure exacerbation in patients with DCM.

Humanin inhibits lymphatic endothelial cells dysfunction to alleviate myocardial infarction-reperfusion injury via BNIP3-mediated mitophagy.

OBJECTIVE: Acute myocardial infarction (AMI) ranks among the top contributors to sudden death and disability worldwide. It should be noted that current therapies always cause increased reperfusion damage. Evidence suggests that humanin (HN) reduces mitochondrial dysfunction to have cardio-protective effects against MI-reperfusion injury. In this context, we hypothesized that HN may attenuate MI-reperfusion injury by alleviating lymphatic endothelial cells dysfunction through the regulation of mitophagy. MATERIALS AND METHODS: In this study, primary lymphatic endothelial cells were selected as the experimental model. Cells were maintained under 1% O2 to induce a hypoxic phenotype. For in vivo experiments, the left coronary arteries of C57/BL6 mice were clamped for 45 min followed by 24 h reperfusion to develop MI-reperfusion injury. The volume of infarcted myocardium in MI-reperfusion injury mouse models were TTC staining. PCR and western blot were used to quantify the expression of autophagy-, mitophagy- and mitochondria-related markers. The fibrosis and apoptosis in the ischemic area were evaluated for Masson staining and TUNEL respectively. We also used western blot to analyze the expression of VE-Cadherin in lymphatic endothelial cells. RESULTS: We firstly exhibited a specific mechanism by which HN mitigates MI-reperfusion injury. We demonstrated that HN effectively reduces such injury in vivo and also inhibits dysfunction in lymphatic endothelial cells in vitro. Importantly, this inhibitory effect is mediated through BNIP3-associated mitophagy. CONCLUSIONS: In conclusion, HN alleviates myocardial infarction-reperfusion injury by inhibiting lymphatic endothelial cells dysfunction, primarily through BNIP3-mediated mitophagy.

An injectable polyacrylamide/chitosan-based hydrogel with highly adhesive, stretchable and electroconductive properties loaded with irbesartan for treatment of myocardial ischemia-reperfusion injury.

Myocardial ischemia-reperfusion injury (MIRI) significantly contributes to the high incidence of complications and mortality associated with acute myocardial infarction. Recently, injectable electroconductive hydrogels (IECHs) have emerged as promising tools for replicating the mechanical, electroconductive, and physiological characteristics of cardiac tissue. Herein, we aimed to develop a novel IECH by incorporating irbesartan as a drug delivery system (DDS) for cardiac repair. Our approach involved merging a conductive poly-thiophene derivative (PEDOT: PSS) with an injectable dual-network adhesive hydrogel (DNAH) comprising a catechol-branched polyacrylamide network and a chitosan-hyaluronic acid covalent network. The resulting P-DNAH hydrogel, benefitting from a high conducting polymer content, a chemically crosslinked network, a robust dissipative matrix, and dynamic oxidation of catechol to quinone exhibited superior mechanical strength, desirable conductivity, and robust wet-adhesiveness. In vitro experiments with the P-DNAH hydrogel carrying irbesartan (P-DNAH-I) demonstrated excellent biocompatibility by cck-8 kit on H9C2 cells and a rapid initial release of irbesartan. Upon injection into the infarcted hearts of MIRI mouse models, the P-DNAH-I hydrogel effectively inhibited the inflammatory response and reduced the infarct size. In conclusion, our results suggest that the P-DNAH hydrogel, possessing suitable mechanical properties and electroconductivity, serves as an ideal IECH for DDS, delivering irbesartan to promote heart repair.

Genetically predicted mood swings increased risk of cardiovascular disease: Evidence from a Mendelian randomization analysis.

BACKGROUND: Mood swings is linked to a higher risk of cardiovascular diseases (CVDs). However, the causal relationships between them remain unknown. METHODS: We conducted this Mendelian randomization (MR) analysis to evaluate the causal associations between mood swings (n = 373,733) and 5 CVDs, including CAD, MI, HF, AF, and stroke using summary data of large-scale genome-wide association studies (GWAS). FinnGen datasets validated the results. Various MR approaches, sensitivity analyses, multivariable MR (MVMR), and two-step MR mediation analyses were applied. RESULTS: The MR analysis revealed significant causal effects of mood swings on CAD (OR = 1.45, 95 % CI 1.24-1.71; P = 5.52e-6), MI (OR = 1.60, 95 % CI 1.32-1.95; P = 1.77e-6), HF (OR = 1.42, 95 % CI 1.18-1.71; P = 2.32e-4), and stroke (OR = 1.48, 95 % CI 1.19-1.83; P = 3.46e-4), excluding AF (P = 0.16). In the reverse MR analysis, no causal relationships were observed. The results were reproducible using FinnGen data. In the MVMR analysis, the causal effects of mood swings on CAD, MI, HF and stroke still remain significant after adjusting potential confounding factors including BMI, smoking and T2DM, but not for LDL and hypertension. Further mediation analysis indicated hypertension may mediate the causal pathways from mood swings to CAD (18.11 %, 95 % CI: 8.83 %-27.39 %), MI (16.40 %, 95 % CI: 7.93 %-24.87 %), HF (13.06 %, 95 % CI: 6.25 %-19.86 %), and stroke (18.04 %, 95 % CI: 8.73 %-27.34 %). CONCLUSION: Mood swings has a significant causal impact on the development of CAD, MI, HF, and stroke, partly mediated by hypertension.

RV1+RV3 Index to Differentiate Idiopathic Ventricular Arrhythmias Arising From Right Ventricular Outflow Tract and Aortic Sinus of Valsalva: A Multicenter Study.

BACKGROUND: This study aimed to investigate the predictive value of parameters of every precordial lead and their combinations in differentiating between idiopathic ventricular arrhythmias (IVAs) from the right ventricular outflow tract and aortic sinus of Valsalva (ASV). METHODS AND RESULTS: Between March 1, 2018, and December 1, 2021, consecutive patients receiving successful ablation of right ventricular outflow tract or ASV IVAs were enrolled. The amplitude and duration of the R wave and S wave were measured in every precordial lead during IVAs. These parameters were either summed, subtracted, multiplied, or divided to create different indexes. The index with the highest area under the curve to predict ASV IVAs was developed, compared with established indexes, and validated in an independent prospective multicenter cohort. A total of 150 patients (60 men; mean age, 45.3±16.4 years) were included in the derivation cohort. The RV1+RV3 index (summed R-wave amplitude in leads V1 and V3) had the highest area under the curve (0.942) among the established indexes. An RV1+RV3 index >1.3 mV could predict ASV IVAs with a sensitivity of 95% and a specificity of 83%. Its predictive performance was maintained in the validation cohort (N=109). In patients with V3 R/S transition, an RV1+RV3 index >1.3 mV could predict ASV IVAs, with an area under the curve of 0.892, 93% sensitivity, and 75% specificity. CONCLUSIONS: The RV1+RV3 index is a simple and novel criterion that accurately differentiates between right ventricular outflow tract and ASV IVAs. Its performance outperformed established indexes, making it a valuable tool in clinical practice.

Case report: Persistent ST-segment elevation due to cardiac metastasis from lung cancer.

Patients with secondary cardiac cancer occasionally show ST segment elevation that mimics acute coronary syndrome despite the absence of coronary artery occlusion. We herein describe a rare case of secondary cardiac cancer that presented with ST-segment elevation. An 82-year-old Chinese man was admitted to the hospital with chest discomfort. Electrocardiography (ECG) showed ST segment elevation in the precordial leads and low-voltage QRS complexes in limb leads without the development of Q waves. Unexpectedly, emergency coronary angiography showed no significant stenosis of the coronary arteries. However, fortunately, transthoracic echocardiography (TTE) revealed massive pericardial effusion and a mass at the apex of the ventricular myocardium. Coincidentally, contrast-enhanced chest computed tomography showed primary lung cancer in the left lower lobe, pericardial effusion, and myocardial metastasis at the ventricular apex. The pericardiac fluid contained blood with significantly increased CEA levels and exfoliated tumor cells. The lung histopathological report suggested squamous cell carcinoma. Two months later, the patient died. These findings suggested that the persistent ST-segment without the development of Q waves was associated with ventricular invasion by primary lung cancer and may indicate a poor prognosis. In conclusion, physicians should be aware of persistent ST-segment elevation mimicking myocardial infarction due to cardiac metastasis with a poor prognosis.

Short-term and long-term effects of cryoballoon ablation versus antiarrhythmic drug therapy as first-line treatment for paroxysmal atrial fibrillation: A systematic review and meta-analysis.

Cryoballoon ablation (CBA) is an effective treatment for drug-refractory atrial fibrillation (AF) patients. Whether CBA as a first-line treatment is superior in the rhythm control of AF than antiarrhythmic drugs (AAD) remains unclear. CBA is superior to AAD as initial therapy for rhythm control of paroxysmal atrial fibrillation (PAF). A comprehensive database search was performed in PubMed, Embase, Cochrane, and Web of Science from inception to March 22, 2023. Treatment efficacy was pooled using risk ratio (RR) and standardized mean difference (SMD) with a 95% confidence interval (CI). This study was registered with Prospero (CRD42023401596). Five randomized-controlled trials involving 923 patients and an observational study were included in this study. The CBA group had a significantly lower overall recurrence rate than the AAD group (CBA vs. AAD: RR = 0.59, 95% CI = 0.49-0.71, p < .05, I2 = 0). The incidence of persistent AF could be better controlled in the CBA group than in the AAD (CBA vs. AAD: RR = 0.17, 95% CI = 0.06-0.49, p < .05, I2 = 0). CBA could improve the quality of life (QoL) of patients better than AAD (CBA vs. AAD: SMD = 0.40, 95% CI = 0.14-0.67, p < .05, I2 = 68.5%). CBA can reduce hospitalization rate significantly than AAD at 36-month follow-up (CBA vs. AAD: RR = 0.29, 95% CI = 0.15-0.58, p < .05, I2 = 0%). Compared to AAD, CBA as first-line therapy could reduce the recurrence rate of atrial arrhythmia and incidence of persistent AF and improve QoL in PAF patients with lower incidences of hospitalization.

The predictive value of Tp-Te interval, Tp-Te/QT ratio, and QRS-T angle of idiopathic ventricular tachycardia in patients with ventricular premature beats.

BACKGROUND: Identify idiopathic ventricular tachycardia in patients with ventricular premature beats was required to have effectively treatment. HYPOTHESIS: The aim of this study is to investigate the predictive value of Tp-Te interval, Tp-Te/QT ratio, and QRS-T angle of idiopathic ventricular tachycardia in patients with idiopathic ventricular premature beats. METHODS: One hundred and seventy-eight patients who had undergone premature ventricular complex/ventricular tachycardia (PVC/VT) ablation between January 1, 2020 and August 30, 2022 constituted our study population as ventricular arrhythmia group. Seventy-five healthy people were selected as control group. Patients with no episode of VT were classified as PVC group, while with any episode of VT that has the same morphology with PVC were classified as PVC with VT group. Patients in PVC with VT group were divided into two groups: nonsustained VT group (duration of any episode of VT below 30 s) and sustained VT group (duration of any episode of VT over 30 s). Tp-Te interval, Tp-Te/QT ratio and QRS-T angle were compared in groups. RESULTS: Tp-Te interval, Tp-Te/QT ratio and patients with increased QRS-T angle in PVC with VT group were higher or more than those in PVC group (p < .001). The value of combined diagnosis of these indexes was higher. Tp-Te interval was longer in the sustained VT group compared to the nonsustained VT group (p = .009). CONCLUSION: Tp-Te interval, Tp-Te/QT ratio, and QRS-T angle may have a predictive value of presence of idiopathic VT in patients with premature beats and the combined prediction of these indexes is more valuable. Tp-Te interval maybe helpful for prediction of sustained idiopathic VT.

MiR-22-3p in exosomes increases the risk of heart failure after down-regulation of FURIN.

Heart failure (HF) is often the inevitable manifestation of myocardial ischemia. Hypoxia can induce cardiomyocytes to express many microRNAs (miRNAs), which are highly expressed in exosomes. In addition, miR-22-3p is a marker in heart failure. Therefore, miR-22-3p was taken as the research object to explore its role and mechanism in HF. HF differentially expressed miRNAs were screened by bioinformatic analysis. The HF rats model was constructed and identified by detecting serum brain natriuretic peptide (BNP) and ultrasound analysis [left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS)]. The extracted exosomes were identified by transmission electron microscopy, and Western blot was used to detect the expressions of Tsg101 and CD63. Quantitative real-time polymerase chain reaction detected miR-22-3p expression in serum, exosomes, and serum without exosomes, while the cardiomyocytes cytotoxicity was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and PKH26 staining. After overexpressing/silencing miR-22-3p in cells, cell viability, apoptosis, and apoptosis-associated markers were detected. Bioinformatic analysis screened the target gene of miR-22-3p, which was verified by dual-luciferase assay. Regulation of miR-22-3p on FURIN was measured by rescue tests. In vivo experiments were verified the above results. MiR-22-3p was identified as the research object. BNP was increased in the model group, while LVEF and LVFS were decreased. MiR-22-3p was overexpressed in HF-treated serum and exosomes. Normal exosomes did not affect cardiomyocyte function, while high concentrations of HF-treated exosomes were cytotoxic. By regulating apoptosis-related genes, overexpressed miR-22-3p inhibited cell activity and promoted cell apoptosis. Silenced miR-22-3p with opposite effects counteracted effects of HF-treated exosomes. FURIN, target gene of miR-22-3p, was negatively regulated by miR-22-3p, while overexpressed FURIN promoted cell activity and inhibited apoptosis. In vivo research was consistent with the results of cell experiments. By regulating FURIN, miR-22-3p in exosomes increases the risk of HF damage.

ECGNet: An Efficient Network for Detecting Premature Ventricular Complexes Based on ECG Images.

BACKGROUND: Preoperative prediction of the origin site of premature ventricular complexes (PVCs) is critical for the success of operations. However, current methods are not efficient or accurate enough. In addition, among the proposed strategies, there are few good prediction methods for electrocardiogram (ECG) images combined with deep learning aspects. METHODS: We propose ECGNet, a new neural network for the classification of 12-lead ECG images. In ECGNet, 609 ECG images from 310 patients who had undergone successful surgery in the Division of Cardiology, the First Affiliated Hospital of Soochow University, are utilized to construct the dataset. We adopt dense blocks, special convolution kernels and divergent paths to improve the performance of ECGNet. In addition, a new loss function is designed to address the sample imbalance situation, whose cause is the uneven distribution of cases themselves, which often occurs in the medical field. We also conduct extensive experiments in terms of network prediction accuracy to compare ECGNet with other networks, such as ResNet and DarkNet. RESULTS: Our ECGNet achieves extremely high prediction accuracy (91.74%) and efficiency with very small datasets. Our newly proposed loss function can solve the problem of sample imbalance during the training process. CONCLUSION: The proposed ECGNet can quickly and accurately realize the multiclassification of PVCs after training with little data. Our network has the potential to be helpful to doctors with a preoperative diagnosis of PVCs. We will continue to collect similar cases and perfect our network structure to further improve the accuracy of our network's prediction.

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.

Analysis of Diurnal Variations in Heart Rate: Potential Applications for Chronobiology and Cardiovascular Medicine.

Circadian factors likely influence the occurrence, development, therapy, and prognosis of cardiovascular diseases (CVDs). To determine the association between the heart rate (HR) diurnal parameters and CVD risks, we designed an analytical strategy to detect diurnal rhythms of HR using longitudinal data collected by clinically used Holter monitors and wearable devices. By combining in-house developed algorithms with existing analytical tools, we obtained trough phase and nocturnal variation in HR for different purposes. The analytical strategy is robust and also sensitive enough to identify variations in HR rhythms influenced by multiple effectors such as jet lag, geological location and altitude, and age from total 211 volunteers. A total of 10,094 sets of 24-h Holter ECG data were analyzed by stepwise partial correlation to determine the critical points of HR trough phase and nocturnal variation. The following HR diurnal patterns correlate with high CVD risk: arrhythmic pattern, anti-phase pattern, rhythmic patterns with trough phase less than 0 (extremely advanced diurnal pattern) or more than 5 (extremely delayed diurnal pattern), and nocturnal variation less than 2.75 (extremely low) or more than 26 (extremely high). In addition, HR trough phases from wearable devices were nearly identical to those from 24-h Holter monitoring from 12 volunteers by linear correlation and Bland-Altman analysis. Our analytical system provides useful information to identify functional diurnal patterns and parameters by monitoring personalized, HR-based diurnal changes. These findings have important implications for understanding how a regular heart diurnal pattern benefits cardiac function and raising the possibility of non-pharmacological intervention against circadian related CVDs. With the rapid expansion of wearable devices, public cardiovascular health can be promoted if the analytical strategy is widely applied.

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.

Differences in sarcoplasmic reticulum Ca²âº leak characteristics between systolic and diastolic heart failure rabbit models.

Diastolic heart failure (DHF) and systolic heart failure (SHF) are two clinical subsets of chronic heart failure (CHF). Sarcoplasmic reticulum (SR) Ca²âº leak has been measured in SHF and might contribute to contractile dysfunction and arrhythmogenesis. However, no study has investigated a similar phenomenon in DHF. Thus, we established DHF and SHF rabbit models and compared the differences in Ca²âº leak between these models. New Zealand white rabbits were randomly divided into three groups (n = 8 in each group): sham operation (SO) group, DHF group and SHF group. Cardiac functions were determined by echocardiography and hemodynamic assays. The SR Ca²âº leak was measured with a calcium-imaging device and the expression and activities of related proteins were evaluated with Western blots and autophosphorylation. In the DHF group, there was significantly increased ventricular wall thickness and stiffness, reduced diastolic function, and total amount of FK506 binding protein 12.6 (FKBP12.6), increased expression and activity of protein kinase A (PKA) and phosphorylation site (P2809) in the ryanodine receptor (RyR2), but no prominent Ca²âº leak. In the SHF group, there was significantly increased ventricular cavity size, reduced systolic function, increased SR Ca²âº leak, reduced total amount of FKBP12.6 and FKBP12.6-RyR2 association, increased expression and activity of PKA and Ca²âº/calmodulin-dependent protein kinase II (CaMKII) and their RyR2 phosphorylation sites with unchanged P2030. Our results suggest that a prominent SR Ca²âº leak was not observed in the DHF model, which may provide a new idea for the reasons in preserved systolic function, and CaMKII possibly plays a more important role in SR Ca²âº leak.

Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway.

Enhanced apoptosis of cardiomyocytes in suffering overloaded saturated fatty acids (SFAs) can result in myocardial infarction and cardiac dysfunction. The function of vascular endothelial growth factor (VEGF) in cardiomyocyte protection was not clearly described. To investigate the preservative effects of VEGF sensitization on ceramide-mediated programmed cell death of cardiomyocytes, palmitate-induced injury in H9c2 cells was established as an in vitro model. Results revealed that 0.5 mM palmitate application effectively led to debased viability and activated apoptotic factors. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h of treatment with 0.5 mM PAL. In addition, cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. Reduced apoptosis rate and expression of caspase 3, Bax, and NF-κB p65 were observed in this process, while boosted Bcl-2, p-JNK/JNK expression and activity of caspase 3 were checked. However, p-ERK/ERK levels did not exhibit a significant change. These findings indicated the protective effects of VEGF in confronting the ceramide-induced cardiomyocyte apoptosis, and would devote therapeutic targets for cardiovascular safeguard in dealing with fatty acid stress.

[Comparison of cardiac function and expression and activity of myocardial calcium regulatory proteins in rabbit systolic and diastolic heart failure models.].

The aim of the present study is to investigate the differences in cardiac function, and the expression and activity of calcium regulatory proteins between rabbit systolic heart failure (SHF) and diastolic heart failure (DHF) models. New Zealand white rabbits were randomly divided into three groups: sham operation (SO) group, DHF group (receiving abdominal aortic constriction) and SHF group (receiving aortic valve destruction and abdominal aortic constriction). The cardiac function was detected by echocardiographic and hemodynamic assays. The mRNA expression levels of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) and phospholamban (PLB) were evaluated by RT-PCR. The protein expression levels of SERCA2a, PLB, phosphoserine 16-PLB (pSer-16-PLB) and protein kinase A (PKA) were evaluated by Western blot, and the phosphorylation status of PLB was determined by the ratio of pSer-16-PLB protein level to that of PLB. The activity of SERCA2a was measured through inorganic phosphate. The activity of PKA was measured by gamma-(32)P ATP-binding assays. Compared with SO group, there were significantly increased ventricular wall thickness, raised left ventricular end diastolic pressure (LVEDP), reduced diastolic function in DHF group (P<0.05 or P<0.01), and significantly increased ventricular cavity size and LVEDP, reduced systolic function in SHF group (P<0.05 or P<0.01). The expression levels of SERCA2a in DHF and SHF groups were lower than that in SO group (P<0.05), while the expression and activity of PKA in DHF and SHF groups were higher than that in SO group (P<0.05 or P<0.01), and there was no significant difference between DHF and SHF groups. The expression levels of PLB and pSer-16-PLB as well as the phosphorylation status of PLB and activity of SERCA2a in SHF group were lower than those in DHF and SO groups respectively. Posing a contrast, the phosphorylation status of PLB and activity of SERCA2a in DHF group were higher than that in SO group (P<0.05). These results indicate that the SHF and DHF models were successfully established, and there are some differences in the expression and activity of calcium regulatory proteins between two models.