Study on the relationship between atrial high-rate episode and left atrial strain in patients with cardiac implantable electronic device.

Background: Although atrial high-rate episode (AHRE) and atrial fibrillation (AF) cannot entirely be identical, recent studies suggest AHRE is linked to AF development and shares some characteristics with AF regarding thromboembolism. At present, there is still lack of predictive indicators for AHRE and diagnostic methods and clinical indicators for AHRE in patients without cardiac implantable electronic device (CIED). The aim of this study was thus to explore the relationship between AHRE and left atrial (LA) strain parameters with the goal of identifying high-risk populations of AHRE by LA strain characteristics. Methods: From February 2022 to May 2023, a total of 105 CIED patients were enrolled and divided into two groups based on whether AHRE had occurred: AHRE (-) group (n=65) and AHRE (+) group (n=40). Real-time three-dimensional echocardiography (RT-3DE) technique was used to obtain the LA time-volume curve. The collected dynamic images were analyzed on the Echopac 204 workstation to obtain the parameters of LA. The four-dimensional automatic LA quantitative analysis (4D Auto LAQ) technology was used to analyze the LA strain parameters: LA reservoir longitudinal strain (LASr), LA conduit longitudinal strain (LAScd), LA contraction longitudinal strain (LASct), LA reservoir circumferential strain (LASr-c), LA conduit circumferential strain (LAScd-c), LA contraction circumferential strain (LASct-c). Correlation analysis was carried out using Binary logistic regression analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the diagnostic performance of LASct in AHRE. Results: Body surface area (BSA) [odds ratio (OR) =8.34, 95% confidence interval (CI): 1.32-72.30, P=0.037], LASct (OR =1.20, 95% CI: 1.05-1.39, P=0.013) and LA end-systolic volume (LAESV) (OR =1.02, 95% CI: 1.00-1.04, P=0.023) were the influencing factors of AHRE. Only LASct (OR =1.18, 95% CI: 1.01-1.38, P=0.041) was found to be an independent influencing factor of AHRE. This result remained significant after adjusting for age, sex, hypertension, diabetes, and stroke history. The ROC curve showed that the cut-off for predicting AHRE was LASct =-4.125% with sensitivity of 37.5% and specificity of 87.7%. Conclusions: This cross-sectional study found that decreased LASct (absolute value) is an independent risk factor for the AHRE and has diagnostic efficacy in certain degree for the occurrence of AHRE.

How the trabeculae protrude within the left atrial appendage is the key factor affecting thrombosis in patients with atrial fibrillation.

The left atrial appendage (LAA) is a major site of thrombosis in patients with non-valvular atrial fibrillation. The myocardial trabeculae within the LAA have a peculiar tendency to protrude but its relationship to thrombosis remains unknown. This study aimed to investigate the relationship between the condition of trabeculae protrusion and LAA thrombosis. This retrospective study consecutively selected patients diagnosed with non-valvular atrial fibrillation and prepared for radiofrequency ablation from January 2011 to May 2020. Patients were divided into the thrombus group (n = 43), the sludge group (n = 35), and the normal group (n = 407) according to whether the thrombus or sludge was present. The trabeculae protruding angle (TPA), which was measured by the CT scans, was used to quantify the trabeculae protrusion condition. Patients' clinical data, TPA, LAA emptying velocity, and other factors were collected and compared among the three groups. A total of 485 patients were enrolled. The range of TPA was between 0 and 158 degrees, with an average of 89.3 ± 35.6 degrees. The TPA was significantly greater in the thrombus (109.3 ± 14.8 degrees) and sludge groups (110.8 ± 12.8 degrees) than in the normal group (85.3 ± 37.1). The incidence of LAA thrombus and sludge increased with increasing TPA. Multivariate regression analysis showed that the TPA was an independent risk factor for LAA thrombus (OR = 1.046, 95%CI: 1.020-1.073, p < 0.001) and sludge (OR = 1.035, 95%CI: 1.017-1.053, p < 0.001). Further analysis revealed that the TPA was negatively correlated with LAA emptying velocity but its effect on promoting thrombosis was not only mediated by slowing down the flow velocity. The TPA can well reflect the condition of trabeculae protrusion. This study revealed that the TPA was an independent risk factor for LAA thrombus or sludge, providing a potential indicator for future thrombosis risk assessment.

Radiofrequency catheter ablation for improving myocardial work in patients with ventricular pre-excitation.

Background: Previous studies have not consistently found significant improvements in left ventricular ejection fraction or global longitudinal strain (GLS) after radiofrequency catheter ablation (RFCA) in patients with ventricular pre-excitation. The aim of this study was thus to explore the effects of RFCA on left ventricular function in patients with ventricular pre-excitation using a new noninvasive echocardiographic method of myocardial work. Methods: A total of 34 patients with ventricular pre-excitation who underwent RFCA and 18 healthy controls were prospectively included in this study. Before and after participants underwent RFCA, electrocardiographic and echocardiographic data of the patients were collected at resting and pacing heart rates (HRs) of 100 beats per minute (bpm) and 120 bpm (controlled by high right atrial pacing during the procedure). Clinical data of the healthy controls at resting HR were also collected. A self-controlled paired sample t test was used to compare the differences before and after participants underwent RFCA. Results: After participants underwent RFCA, the global wasted work (GWW) of the included patients decreased (resting HR: 165.3±68.8 vs. 92.6±42.5 mmHg%, P<0.001; HR of 100 bpm: 276.3±121.2 vs. 187.9±96.0 mmHg%, P<0.001; HR of 120 bpm: 323.9±126.7 vs. 181.0%±74.3 mmHg%. P<0.001), while the global work efficiency (GWE) increased (resting HR: 91.5%±3.8% vs. 94.9%±1.6%; P<0.001; HR of 100 bpm: 87.0%±5.2% vs. 91.0%±3.3%, P<0.001; HR of 120 bpm: 85.0%±5.1% vs. 90.3%±3.7%, P<0.001). Conclusions: In patients with ventricular pre-excitation, impaired GWW and GWE can be improved with RFCA. In clinical practice, noninvasive myocardial work assessment can be used in patients with ventricular pre-excitation.

Left bundle branch pacing on mechanical synchrony and myocardial work in bradycardia patients.

Left bundle branch pacing (LBBP) has emerged as a novel physiological pacing method to produce narrower QRS duration, but whether it could restore mechanical synchrony and improve myocardial work still lacks sufficient evidence. Therefore, the goal of this study was to evaluate mechanical synchrony and myocardial work in LBBP. We collected 20 patients with LBBP due to symptomatic bradycardia and another 29 age-matched patients with right ventricular pacing (RVP). For LBBP patients, cardiac electro-mechanical synchrony and myocardial work were measured at baseline and 7 days after implantation and compared with the RVP patients. In the LBBP group, paced QRS duration and mechanical synchrony were not significantly different from baseline(all P > 0.05), but significantly smaller than that in the RVP group (all P<0.05). Meanwhile, global longitudinal strain (GLS) in LBBP was greater than that in the RVP group (17.7 ± 3.5% vs. 14.8 ± 3.1%, P < 0.05). Global myocardial work index and global constructive work were also better than that in the RVP group(all P<0.05). Global work efficiency was 91.9 ± 3.1%, which was greater when compared with RVP (P < 0.05). LBBP provides better cardiac electro-mechanical synchrony and more effective myocardial work than that in RVP, thus improving global heart function.

Changes in echocardiographic parameters of the donor's heart before and after heart transplantation and their relationship with post-transplant survival.

Background: Heart transplantation is now widely performed in China, but the current entry criteria for heart transplantation donors are simple and lack reliable standards; there are still no studies on the effect of preoperative echocardiographic parameters of heart transplantation donors on the prognosis of the recipient. Therefore, the aim of this study is twofold: (I) to observe the characteristics of changes in echocardiographic parameters of the donor's heart before and after heart transplantation and (II) to study the relationship between the changes in echocardiographic parameters of the donor's heart pre- and post-transplant and transplant recipient survival. Methods: A total of 29 patients who underwent orthotopic heart transplant in our hospital from October 2016 to October 2019 were enrolled in this study. All recipients were followed up until April 2020. Echocardiographic data were collected pre-transplantation (donor) and at 1 week and 1 month post-transplant (recipient). Results: Compared with the pretransplanted donor's heart, there was an increase in the interventricular septal diameter, left ventricular posterior wall diameter, right atrium diameter and right ventricular diameter, while a decrease was found in the tricuspid annular systolic displacement and tricuspid annular peak systolic velocity at 1 week post-transplant. The survival curve showed that the postoperative survival time in the right atrium/ventricle ≥32 mm group was better than that in the right atrium/ventricle <32 mm group. The survival curve also showed that the postoperative survival time in the right atrium/ventricle enlargement <2 mm group was better than that in the right atrium/ventricle enlargement ≥2 mm group. Conclusions: In the early post-transplant period, ventricular myocardial thickening, right heart enlargement and a decrease in right heart function were observed in the post-transplanted heart compared to the pretransplanted donor's heart. Postoperative survival was higher among heart transplant patients who received a heart with right atrium/ventricle ≥32 mm. Postoperative survival was lower among heart transplant patients whose right atrium/ventricle was dilated ≥2 mm at 1 month postoperatively compared with the pretransplanted donor's heart.

Association of latent class analysis-derived subphenotypes of acute kidney injury with mortality in critically ill patients with cardiovascular disease: a retrospective cohort study.

BACKGROUND: To explore the potential heterogeneity of acute kidney injury (AKI) and evaluate the prognostic differences among AKI subphenotypes in critically ill patients with cardiovascular diseases. METHODS: Data were extracted from the Medical Information Mart for Intensive Care (MIMIC)-III database. Latent class analysis (LCA) was used to explore the potential subphenotypes of AKI in critically ill patients with cardiovascular diseases. The number of classes was identified by the Bayesian information criterion and entropy. The differences in prognostic ability among the AKI subphenotypes were evaluated by logistic regression analysis. RESULT: A total of 7738 AKI patients were enrolled in this study. Using LCA, AKI patients were divided into 4 heterogeneous subphenotypes, which were obviously different from the Kidney Disease: Improving Global Outcomes (KDIGO) stages. Interestingly, class 3 classified by LCA was dominated by stage 2, while the mortality rate in class 3 was significantly different from that in class 1 (15.2% vs. 1.6%, p < 0.05). After further adjustment, the mortality rate in class 3 remained higher than that in class 1, with an odds ratio of 12.31 (95% confidence interval, 8.96-16.89). CONCLUSIONS: LCA was feasible for AKI classification in critically ill patients with cardiovascular disease, and 4 distinct subphenotypes of AKI patients with different prognoses were identified. Our results highlighted the potential heterogeneity of AKI patients, which is worthy of further investigation.

Mechanical Synchrony and Myocardial Work in Heart Failure Patients With Left Bundle Branch Area Pacing and Comparison With Biventricular Pacing.

Background: Little is known about the efficacy of permanent left bundle branch area pacing (LBBAP) in delivering cardiac resynchronization therapy (CRT). This study aimed to evaluate the effect of LBBAP on mechanical synchronization and myocardial work (MW) in heart failure (HF) patients and to compare LBBAP with biventricular pacing (BVP). Methods: This is a multicenter, prospective cohort study. From February 2018 to January 2021, 62 consecutive HF patients with reduced ejection fraction (LVEF ≤ 35%) and complete left bundle branch block (CLBBB) who underwent LBBAP or BVP were enrolled in this study. Echocardiograms and electrocardiograms and were conducted before and 3-6 months after implantation. Intra- and interventricular synchronization were assessed using two-dimensional speckle tracking imaging (2D-STI). The left ventricular pressure-strain loop was obtained by combining left ventricular strain with non-invasive blood pressure to evaluate mechanical efficiency. Results: The echocardiographic response rates were 68.6 and 88.9% in the BVP and LBBAP groups, respectively. Left bundle branch area pacing resulted in significant QRS narrowing (from 177.1 ± 16.7 to 113.0 ± 18.4 ms, P < 0.001) and improvement in LVEF (from 29.9 ± 4.8 to 47.1 ± 8.3%, P < 0.001). The global wasted work (GWW) (410.3 ± 166.6 vs. 283.0 ± 129.6 mmHg%, P = 0.001) and global work efficiency (GWE) (64.6 ± 7.8 vs. 80.5 ± 5.7%, P < 0.001) were significantly improved along with shorter peak strain dispersion (PSD) (143.4 ± 45.2 vs. 92.6 ± 35.1 ms, P < 0.001) and interventricular mechanical delay (IVMD) (56.4 ± 28.5 vs. 28.9 ± 19.0 ms, P < 0.001), indicating its efficiency in improving mechanical synchronization. In comparison with BVP, LBBAP delivered greater improvement of QRS narrowing (-64.1 ± 18.9 vs. -32.5 ± 22.3 ms, P < 0.001) and better mechanical synchronization and efficiency. Conclusions: Left bundle branch area pacing was effective in improving cardiac function, mechanical synchronization, and mechanical efficiency and may be a promising alternative cardiac resynchronization therapy.

Assessment of atrial septal defect using 2D or real-time 3D transesophageal echocardiography and outcomes following transcatheter closure.

BACKGROUND: The assessment of interatrial septum (IAS) requires a standardized, systematic approach, including two-dimensional transthoracic echocardiography (2D TTE), 2D transesophageal echocardiography (2D TEE), and three-dimensional (3D) TEE. Although 2D TEE has been widely used for the preoperative assessment of atrial septal defect (ASD), its ability to provide reliable information is often limited due to the structural characteristics of IAS. The introduction of 3D TEE provides a unique "en face" view of IAS, which allows the visualization and accurate measurements of diameters, area, and rims of ASD. Hence, appropriate ASD imaging information is particularly important in successful transcatheter closure. METHODS: In this retrospective study, 2D TTE/TEE, and 3D TEE were performed before ASD closure, with 2D minimal and maximal diameters, areas, and residual rims being recorded. Adequate 3D TEE imaging data sets were collected and then analyzed. ASD related parameters were compared using different echocardiography. Patients who underwent ASD closure completed a clinical follow-up. RESULTS: The mean defect maximal diameter and aperture area by 3D TEE was significantly larger than that of the corresponding 2D TEE (P<0.05). There was no statistical difference in the minimal and maximal diameter or area by TEE for circular-shaped ASDs. For oval ASDs, mean minimal diameter on 2D TEE was larger than that on 3D TEE. The mean maximal diameter measured using 2D TEE was smaller than the 3D TEE measurement (16.0±7.1 vs. 19.8±8.6; P<0.05). For complex-shaped defects, there were statistical differences in minimal and maximal diameter between TEEs. Furthermore, 2D and 3D TEE had a longer superior vena cava (SVC) residual rim than did 2D TTE (P<0.05). The 3D TEE residual rims of the inferior vena cava (IVC) was significantly larger than the corresponding 2D TEE. There was a very strong correlation between the residual rim measurements using 3D and 2D TEE. However, the limits of agreement between 2D and real-time 3D TEE measurements were more apparent in the IVC rim group than in the other groups. CONCLUSIONS: Our study confirms the value of 3D TEE in assessing ASD shape and size reported by previous studies, and is also the first to accurately and systematically characterize ASD residual rim in complex ASDs.

Mental health is correlated with lipoprotein(a) levels in male patients with premature coronary heart disease.

BACKGROUND: High levels of lipoprotein(a) (Lp(a)) is an independent risk factor for premature coronary heart disease (PCHD). It is also considered a residual risk for controlled low density lipoprotein cholesterol (LDL-C). Dietary control, exercise, and drugs have limited effects on the levels of Lp(a). Recently, mental health was found to be associated with lipid levels and increased risk of PCHD. However, the relationship between mental health and Lp(a) is still unknown. This study explored the association between mental health and Lp(a) levels in men with PCHD. METHODS: A retrospective, observational study was conducted. A total of 226 male patients with PCHD, aged 49.65±3.68 years, was included in this study. The control group consisted of 230 age-matched healthy male volunteers. Serum Lp(a) levels ≥30 mg/dL, as measured by the immunoturbidimetry method, were considered high. All participants received health related quality of life (HRQoL) scores using the self-assessed 36-Item Short Form Health Survey (SF-36). The HRQoL includes both a physical component summary (PCS) and a mental component summary (MCS). RESULTS: Patients with PCHD were found to have higher levels of Lp(a) (51.61±33.39 vs. 26.42±21.93, P<0.001), and lower MCS (35.83±4.21 vs. 39.85±4.12) and PCS scores (38.02±3.73 vs. 39.63±3.21) compared to healthy volunteers. The MCS score was negatively correlated with Lp(a) levels in the PCHD group (R=-0.295, P<0.001), but no correlation was detected in the control group. There was no relationship between the PCS score and Lp(a) levels in neither the PCHD group nor the healthy control group. Multivariate logistic regression analysis indicated that the MCS and PCS scores were negatively correlated with the risk of PCHD. CONCLUSIONS: These findings suggested that poor mental health may be associated with high levels of Lp(a) and increased risk of PCHD in men. Therefore, improving the mental state in men with PCHD may be crucial.

3D transesophageal echocardiography assists in evaluating the morphology, function, and presence of thrombi of left atrial appendage in patients with atrial fibrillation.

BACKGROUND: Left atrial appendage (LAA) is significantly more likely to form thrombi in patients with atrial fibrillation (AFib). Two-dimensional transesophageal echocardiography (2D TEE) is considered the gold standard for assessing and studying LAA morphology and anatomy. However, 2D TEE can only visualize one plane at any given time. Real-time three-dimensional echocardiography (RT-3D TEE) imaging can preserve spatial and temporal resolution, which is a safe, accurate, and reproducible imaging modality. There are few reports of the usage of RT-3D TEE to study LAA in AFib patients. In our research, RT-3D TEE helps to provide detailed LAA information and identifying the presence or absence of thrombi from pectinate muscles in paroxysmal and long-standing AFib patients. METHODS: LAA morphology was analyzed in detail by 2D TEE and RT-3D TEE in 320 patients with paroxysmal or long-standing AFib. The LAA flow pattern, as maximal LAA emptying flow velocity (LAAeV), was retrieved from 2D and 3D TEE imaging. LAA morphological parameters, spontaneous echo contrast (SEC), and thrombi were also detected by 2D and 3D TEE in all patients. In addition, LAA lobes and types were classified according to the morphology by 3D TEE, and the relationship between LAA types and the incidence of thrombi was evaluated. RESULTS: Long-standing AFib had greater enlargement of LAAs (orifice diameters and area), significantly more severe SEC, and a higher thrombi clot incidence rate by 3D-TEE compared with paroxysmal AFib patients (P<0.05). In addition, cauliflower morphology in long-standing AFib patients was associated with a higher LAA thrombus (OR 2.1, 95% CI: 1.1-8.5, P=0.031) and increased prevalence of SEC. Moreover, the uncertainty of thrombi detection was significantly decreased by 3D TEE compared with 2D TEE (P<0.001), and the certainty of thrombi detection by 3D TEE also decreased slightly (P=0.06). CONCLUSIONS: RT-3D TEE is a safe and real-time option for the evaluation of LAA morphology and function. Long-standing AFib has greater LAA and SEC, as well as a higher incidence of thrombi than the paroxysmal group. Cauliflower LAA type was associated with a higher prevalence of SEC and thrombi.

Klotho gene improves oxidative stress injury after myocardial infarction.

The aim of the present study was to investigate the effects and mechanisms of the Klotho gene in oxidative stress injury after myocardial infarction. Sprague-Dawley rats were divided into five groups (sham, model, pDC316, LY294002, and pDC316-Klotho). Subsequently, the superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA) concentrations were measured in myocardial tissues. Additionally, pathological differences among the groups were evaluated using hematoxylin and eosin and Masson's trichrome staining. Apoptosis was assayed by terminal deoxynucleotidyl transferase 2'-deoxyuridine-5'-triphosphate nick end-labeling assay, evaluated Klotho protein expression by immunohistochemical assay, and assessed Nrf 2 and ARE protein expressions using western blotting assay. As compared with in the sham group, the SOD, MDA, and GSH concentrations were significantly deteriorated (P<0.001, respectively); cardiomyocyte apoptosis index values were significantly increased (P<0.001); Klotho protein expression was significantly depressed; and Nrf-2 and ARE protein expressions were significantly (P<0.001, respectively) in the model and pDC316 groups. However, with Klotho supplementation by pDC316 transfection, as compared with in the model group, the SOD, MDA, and GSH concentrations were significantly improved (P<0.001, respectively); the cardiomyocyte apoptosis index values were significantly suppressed (P<0.001); and the pathology was improved. Further, the Klotho protein expression of the pDC316-Klotho group was significantly upregulated and the Nrf-2 and ARE proteins expressions of the LY294002 and pDC316-Klotho groups were significantly suppressed. Klotho overexpression improved findings of oxidative stress injury after myocardial infarction.

Association of renal cyst and type A acute aortic dissection with hypertension.

BACKGROUND: Type A acute aortic dissection (TA-AAD) has high mortality, with 50% of patients dying before hospital admission. Hypertension is the most common comorbidity for acute aortic dissection, and effective antihypertensive therapy is still unable to predict the risk of aortic rupture at the medium- and long-term stages. While the presence of renal cyst has been found to increases the risk of thoracic aortic disease, the correlation between renal cyst and TA-AAD with hypertension remains poorly understood. Thus, this study aimed to determine the relationship of renal cyst and TA-AAD with hypertension. METHODS: A retrospective analysis was performed in 464 hypertension patients from August 2014 to August 2019. A total of 230 TA-AAD patients were enrolled in the AD with hypertension group (age 53.79±11.31 years, male 90.87%), and matched by age, sex, and hypertension control to 234 patients without TA-AAD who were enrolled in the non-AD with hypertension group. Patients were divided into three subgroups according to the numbers of renal cysts: no renal cyst, single renal cyst, and multiple renal cysts. RESULTS: In this study, the AD with hypertension group had significantly more single renal cyst and multiple renal cyst cases than did the non-AD with hypertension group. The mean age of the multiple renal cyst subgroup was significantly older than that of the single renal cyst subgroup (57.25±13.00 vs. 51.57±10.75 years) in the AD with hypertension group. There was significantly different distribution of dissection starting points and dissection ending points across three renal cyst subgroups. Multivariate logistic regression analysis indicated that having no renal cyst significantly decreased the risk of TA-AAD in middle-aged and elderly patents, but showed no correlations with those of younger ages. Single renal cyst status also significantly decreased the risk of TA-AAD in elderly patients [odds ratio (OR) =0.129, 95% confidence interval (CI): 0.029-0.575, P=0.007]. CONCLUSIONS: Renal cyst status correlates with the risk of TA-AAD with hypertension in middle-aged and elderly patients, and exhibits different degrees of vascular lesion in aortic dissection. We therefore suggest that different antihypertensive standards should be adopted in different renal cyst status to more effectively prevent aortic dissection.

Assessment of Cardiac Lead Perforation: Comparison Among Chest Radiography, Transthoracic Echocardiography and Electrocardiography-gated Contrast-enhanced Cardiac CT.

OBJECTIVES: Cardiac lead perforation is a rare but potentially life-threatening event. The purpose of this study was to investigate the diagnostic performances of chest radiography, transthoracic echocardiography (TTE) and electrocardiography (ECG)-gated contrast-enhanced cardiac CT in the assessment of cardiac lead perforation. METHODS: This retrospective study was approved by the ethics review board of Sun Yat-Sen Memorial Hospital at Sun Yat-Sen University (Guangzhou, China), and the need to obtain informed consent was waived. Between May 2010 and Oct 2017, 52 patients were clinically suspected to have a cardiac lead perforation and received chest radiography, TTE and ECG-gated contrast-enhanced cardiac CT. Among them, 13 patients were identified as having cardiac lead perforation. The diagnostic performances of these three modalities were evaluated by receiver-operating characteristic (ROC) curves using a composite reference standard of surgical and electrophysiological results and clinical follow-up. The areas under ROCs (AUROCs) were compared with the McNemar test. RESULTS: The accuracies of chest radiography, TTE and ECG-gated contrast-enhanced cardiac CT imaging for the diagnosis of cardiac lead perforation were 73.1%, 82.7% and 98.1%, respectively. ECG-gated contrast-enhanced cardiac CT had a higher AUROC than chest radiography (p < 0.001) and TTE (p < 0.001). CONCLUSIONS: ECG-gated contrast-enhanced cardiac CT is superior to both chest radiography and TTE imaging for the assessment of cardiac lead perforation. KEY POINTS: • ECG-gated contrast-enhanced cardiac CT has an accuracy of 98.1% in the diagnosis of cardiac lead perforation. • The AUROC of ECG-gated contrast-enhanced cardiac CT is higher than those of chest radiography and TTE imaging. • ECG-gated contrast-enhanced cardiac CT imaging has better diagnostic performance than both chest radiography and TTE imaging for the assessment of cardiac lead perforation.

Stretch-activated channel Piezo1 is up-regulated in failure heart and cardiomyocyte stimulated by AngII.

Mechanotransduction is the conversion of extracellular mechanical stimuli into intracellular biochemical signals, and plays an important role in heart responses to its own mechanical environment. Piezo1 as a distinct stretch-activated channel (SAC) in mammal involves in not only vascular remodeling during embryonic development but also arterial remodeling upon to hypertension at adult stage. In the present study, the expression of Piezo1 was up-regulated in failure heart induced by myocardial infarction (MI) by real-time PCR, Western blot and immunohistochemistry analysis. Expression of Piezo1 mRNA and protein was enhanced by AngiotensinII (AngII) in neonatal rat ventricular myocytes via AT1 receptor depended methods. Furthermore, the Piezo1 expression was attenuated by Erk1/2 chemical inhibitor (U0126) only, but not by p38 MAPK inhibitor (SB203580), or JNK inhibitor (SP600125). Finally, systolic function improvement followed by chronic treatment with angiotensin receptor blocker (ARB) losartan prevented Piezo1 up-regulation in failure heart in vivo. In conclusion, our studies linked mechanotransduction which involved renin-angiotensin system that mediated up-regulation of Piezo1 to a clinically relevant heart failure.

Apelin promotes mesenchymal stem cells survival and vascularization under hypoxic-ischemic condition in vitro involving the upregulation of vascular endothelial growth factor.

BACKGROUND: Mesenchymal stem cells (MSCs) transplantation has been regarded as an optimal therapeutic approach for cardiovascular disease. However, the inferior survival and low vascularization potential of these cells in the local infarct site reduce the therapeutic efficacy. In this study, we investigated the influence of apelin on MSCs survival and vascularization under hypoxic-ischemic condition in vitro and explored the relevant mechanism. METHODS: MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells of the third passage were divided into MSCs and MSCs+apelin groups. In the MSCs+apelin group, MSCs were stimulated with apelin-13 (5µM). The two groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24h, using normoxia (20% O2) as a negative control during the process. Human umbilical vein endothelial cells (HUVECs) were used and incubated with conditioned media from both groups to promote vascularization for another 6h. Vascular densities were assessed and relevant biomarkers were detected thereafter. RESULTS: Compared with MSCs group, MSCs+apelin group presented more rapid growth. The proliferation rate was much higher. Cells apoptosis percentage was significantly declined both under normoxic and hypoxic conditions. Media produced from MSCs+apelin group triggered HUVECs to form a larger number of vascular branches on matrigel. The expression and secretion of vascular endothelial growth factor (VEGF) were significantly increased. CONCLUSION: Apelin could effectively promote MSCs survival and vascularization under hypoxic-ischemic condition in vitro, and this procedure was associated with the upregulation of VEGF. This study provides a new perspective for exploring novel approaches to enhance MSCs survival and vascularization potential.

Long noncoding RNA Braveheart promotes cardiogenic differentiation of mesenchymal stem cells in vitro.

BACKGROUND: Mesenchymal stem cells (MSCs) have limited potential of cardiogenic differentiation. In this study, we investigated the influence of long noncoding RNA Braveheart (lncRNA-Bvht) on cardiogenic differentiation of MSCs in vitro. METHODS: MSCs were obtained from C57BL/6 mice and cultured in vitro. Cells were divided into three groups: blank control, null vector control, and lncRNA-Bvht. All three groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 h, and 24 h of reoxygenation (20% O2). Cardiogenic differentiation was induced using 5-AZA for another 24 h. Normoxia (20% O2) was applied as a negative control during the whole process. Cardiogenic differentiation was assessed, and expressions of cardiac-specific transcription factors and epithelial-mesenchymal transition (EMT)-associated biomarkers were detected. Anti-mesoderm posterior1 (Mesp1) siRNA was transfected in order to block its expression, and relevant downstream molecules were examined. RESULTS: Compared with the blank control and null vector control groups, the lncRNA-Bvht group presented a higher percentage of differentiated cells of the cardiogenic phenotype in vitro both under the normal condition and after hypoxia/re-oxygenation. There was an increased level of cTnT and α-SA, and cardiac-specific transcription factors including Nkx2.5, Gata4, Gata6, and Isl-1 were significantly upregulated (P < 0.01). Expressions of EMT-associated genes including Snail, Twist and N-cadherin were much higher (P < 0.01). Mesp1 exhibited a distinct augmentation following lncRNA-Bvht transfection. Expressions of relevant cardiac-specific transcription factors and EMT-associated genes all presented a converse alteration in the condition of Mesp1 inhibition prior to lncRNA-Bvht transfection. CONCLUSION: lncRNA-Bvht could efficiently promote MSCs transdifferentation into cells with the cardiogenic phenotype in vitro. It might function via enhancing the expressions of cardiac-specific transcription factors and EMT-associated genes. Mesp1 could be a pivotal intermediary in the procedure.

Long noncoding RNAs: Novel molecules in cardiovascular biology, disease and regeneration.

Remarkable breakthroughs made in genomic technologies have facilitated the discovery of thousands of novel transcripts that do not template protein synthesis. Numerous RNAs termed as long noncoding RNAs (lncRNAs) generated from this pervasive transcription function vividly in gene regulatory networks and a variety of biological and cellular processes. Here, we make a brief description of the known and putative functions of lncRNAs in cardiovascular biology and disease. The association between lncRNAs and stem cells mediated cardiomyocytes differentiation and neovascularization is discussed then. It will provide a new clue for further studies on these novel molecules in cardiovascular disease and bring bright prospects for their future applications in cardiac regenerative medicine.

Cardiac stem cells transplantation enhances the expression of connexin 43 via the ANG II/AT1R/TGF-beta1 signaling pathway in a rat model of myocardial infarction.

BACKGROUND: In this study, we hypothesized that CSCs mediated the expression of Cx43 after transplantation post MI via the ANG II/AT1R/TGF-beta1 signaling pathway. METHODS: Myocardial infarction (MI) was induced in twenty male Sprague-Dawley rats. The rats were randomized into two groups and were then received the injection of 5 × 10(6) CSCs labeled with PKH26 in phosphate buffer solution (PBS) or equal PBS alone into the infarct anterior ventricular free wall two weeks after MI. Six weeks later, relevant signaling molecules involved were all examined. RESULTS: In the CSCs group, an increased expression of Cx43 could be observed in different zones of the left ventricle (P<0.01). There was a significant reduction of the angiotensin II (ANG II) level in plasma and different regions of the left ventricular cardiac tissues (P<0.05; P<0.01). The angiotensin II type I receptor (AT1R) was decreased accompanied with an enhanced expression of angiotensin II type II receptor (AT2R) (P<0.01). Transforming growth factor beta-1(TGF-beta1) was downregulated (P<0.01). The expression of mothers against decapentaplegic homolog (SMAD) proteins including SMAD2 and SMAD3 was attenuated whereas SMAD7 was elevated (P<0.01, P<0.01, P<0.05). In addition, the expression of mitogen-activated protein kinases (MAPKs) including extracellular kinases 1/2 (ERK1/2) and p38 was also found to be reduced (P<0.01). CONCLUSION: CSCs transplantation could enhance the level of Cx43 after MI. They might function through intervening the ANGII/AT1R/TGF-beta1 signaling pathway to regulate the expression of Cx43.

Peroxisome Proliferator-Activated Receptor Gamma Promotes Mesenchymal Stem Cells to Express Connexin43 via the Inhibition of TGF-ß1/Smads Signaling in a Rat Model of Myocardial Infarction.

BACKGROUND: In this study, we hypothesized that activation of PPAR-γ enhanced MSCs survival and their therapeutic efficacy via upregulating the expression of Cx43. METHODS: MI was induced in 50 male Sprague-Dawley rats. The rats were randomized into five groups: MI group and four intervention groups, including the MSCs group, combined therapy group (MSCs+ pioglitazone), pioglitazone group and PBS group. Two weeks later, 5 × 10(6) MSCs labeled with PKH26 in PBS were injected into the infarct anterior ventricular free wall in the MSCs and combined therapy groups, and PBS alone was injected into the infarct anterior ventricular free wall in the PBS group. Pioglitazone (3 mg/kg/day) was given to the combined therapy and pioglitazone groups by oral gavage at the same time for another 2 weeks. Myocardial function and relevant signaling molecules involved were all examined thereafter. RESULTS: Heart function was enhanced after MSCs treatment for 2 weeks post MI. A significant improvement of heart function was observed in the combined therapy group in contrast to the other three intervention groups. Compared with the MSCs group, there was a higher level of PPAR-γ in the combined therapy group; Cx43 was remarkably increased in different regions of the left ventricle; TGF-ß1 was decreased in the infarct zone and border zone. To the downstream signaling molecules, mothers against Smad proteins including Smad2 and Smad3 presented a synchronized alteration with TGF-ß1; no differences of the expressions of ERK1/2 and p38 could be discovered in the left ventricular cardiac tissue. CONCLUSIONS: MSCs transplantation combined with pioglitazone administration improved cardiac function more effectively after MI. Activation of PPAR-γ could promote MSCs to express Cx43. Inhibition of TGF-ß1/Smads signaling pathway might be involved in the process.

microRNA-378 promotes mesenchymal stem cell survival and vascularization under hypoxic-ischemic conditions in vitro.

INTRODUCTION: Mesenchymal stem cells (MSCs) transplantation has been demonstrated to be an effective strategy for the treatment of cardiovascular disease. However, the low survival rate of MSCs at local diseased tissue reduces the therapeutic efficacy. We therefore investigated the influence of MicroRNA-378 (miR-378) transfection on MSCs survival and vascularization under hypoxic-ischemic condition in vitro. METHODS: MSCs were isolated from bone marrow of Sprague-Dawley rats and cultured in vitro. The third passage of MSCs were divided into the miR-378 group and control group. For the miR-378 group, cells were transfected with miR-378 mimic. Both groups experienced exposure to hypoxia (1% O2) and serum deprivation for 24 hours, using normoxia (20% O2) as a negative control during the process. After 24 hours of reoxygenation (20% O2), cell proliferation and apoptosis were evaluated. Expressions of apoptosis and angiogenesis related genes were detected. Both groups were further co-cultured with human umbilical vein endothelial cells to promote vascular differentiation for another 6 hours. Vascular density was assessed thereafter. RESULTS: Compared with the control group, MSCs transfected with miR-378 showed more rapid growth. Their proliferation rates were much higher at 72 h and 96 h under hypoxic condition (257.33% versus 246.67%, P <0.01; 406.84% versus 365.39%, P <0.05). Cell apoptosis percentage in the miR-378 group was significantly declined under normoxic and hypoxic condition (0.30 ± 0.10% versus 0.50 ± 0.10%, P <0.05; 0.60 ± 0.40% versus 1.70 ± 0.20%, P <0.01). The miR-378 group formed a larger number of vascular branches on matrigel. BCL2 level was decreased accompanied with an upregulated expression of BAX in the two experimental groups under the hypoxic environment. BAX expression was reduced in the miR-378 group under the hypoxic environment. In the miR-378 group, there was a decreased expression of tumor necrosis factor-α on protein level and a reduction of TUSC-2 under normoxic environment. Their expressions were both downregulated under hypoxic environment. For the angiogenesis related genes, enhanced expressions of vascular endothelial growth factorα, platelet derived growth factor-ß and transforming growth factor-ß1 could be detected both in normoxic and hypoxic-ischemic conditions. CONCLUSION: MiR-378 transfection could effectively promote MSCs survival and vascularization under hypoxic-ischemic condition in vitro.