Real-time 3D-3D image fusion of CTA/CBCT roadmap fluoroscopy in the transcatheter mitral intervention.

Absence of periprocedural visualization of three-dimensional (3D) left heart anatomy and its surrounding structures in fluoroscopy may reduce the rate of successful transcatheter mitral valve repair. We proposed a multimodal imaging strategy based on 3D computed tomography (CT) angiography and 3D cone beam CT fusion images, which enabled real-time visual inspection of 3D cardiac structures on fluoroscopy, to optimize transcatheter mitral intervention. This new image fusion technology, together with standard transesophageal echocardiography guidance, improved the efficiency and safety of the procedure, and could be considered as a new workflow for transcatheter mitral valve intervention.

Angioplasty Guidewire-Assisted vs. Conventional Transseptal Puncture for Left Atrial Appendage Occlusion: a multicentre randomized controlled trial.

AIMS: This study was performed to compare the usability, efficiency, and safety of a modified angioplasty guidewire-assisted transseptal puncture (TSP) technique vs. the conventional approach in facilitating access into the left atrium during left atrial appendage occlusion (LAAO) procedures for the treatment of atrial fibrillation. METHODS AND RESULTS: The ADVANCE-LAAO trial (Angioplasty Guidewire-Assisted vs. Conventional Transseptal Puncture for Left Atrial Appendage Occlusion) was an investigator-initiated, prospective, multicentre, randomized controlled trial (NCT05125159). Patients with atrial fibrillation who underwent LAAO were prospectively enrolled from four centres and randomly assigned to an angioplasty guidewire-assisted TSP group (n = 131) or to a conventional Brockenbrough needle TSP group (n = 132). The primary endpoint was the one-time success rate of TSP. We also analysed the TSP procedure time, failure rate of the assigned TSP type, radiation dose, contrast dose, and procedural complications in both groups. All patients in the guidewire-assisted group underwent successful TSP, whereas five in the standard conventional group switched to the guidewire-assisted approach. The guidewire-assisted puncture improved the one-time success rate (92.4 vs. 77.3%, P = 0.001), shortened the TSP procedure time (109.2 ± 48.2 vs. 120.5 ± 57.6 s, P = 0.023), and tended to have a higher rate of good coaxial orientation of the sheath with the left atrial appendage during the LAAO procedure (66.4 vs. 54.5%, P = 0.059). No TSP-related complications occurred in the guidewire-assisted TSP group, whereas two complications occurred in the conventional TSP group. There was no significant difference in the failure rate of the assigned TSP type, the total procedure time, the total radiation dose, the rate of successful LAAO implantation, or the procedural complication rate between the two groups (all P > 0.05). CONCLUSION: This study confirmed that angioplasty guidewire-assisted puncture can effectively improve the success rate of TSP during LAAO procedures. This novel technique has high potential for application in interventional therapies requiring TSP.

Pulmonary vein perforation into the respiratory tract with systemic air embolism: a rare complication of left atrial appendage closure.

BACKGROUND: Pulmonary vein perforation is an uncommon complication during cardiac intervention. We present a rare case of pulmonary vein perforation into the respiratory tract with systemic air embolism during left atrial appendage closure (LAAC). CASE PRESENTATION: A 77-year-old man with persistent nonvalvular atrial fibrillation was referred for percutaneous LAAC under local anaesthesia (CHA2DS2-VASc score of 4, HAS-BLED score of 3, and prior ischaemic stroke). During the procedure, after delivering a super-stiff guidewire into the left superior pulmonary vein (LSPV), the patient suddenly developed a severe cough with haemoptysis upon advancement of a delivery sheath along the guidewire. Fluoroscopy showed signs of blood entering the left main bronchus, and fast transthoracic echocardiography revealed bubbles in the left heart without pericardial effusion. The procedure was terminated because of a major complication indicated by the repeated haemoptysis and headache, and haemostatic drugs were immediately administered. Subsequent chest computed tomography angiography (CTA) revealed a filling defect in the LSPV branches and bubbles in the aorta. The patient was transferred to the critical care unit for haemostasis and antibacterial treatment. Transthoracic echocardiography later that day showed no bubbles in the heart. The headache and haemoptysis significantly abated the following day. The bubbles in the aorta disappeared on chest CTA 7 days later. CONCLUSIONS: Interventional cardiologists should pay attention to anatomical variations of the pulmonary vein, which are associated with a high risk of complications of pulmonary vein perforation during LAAC. Preoperative CTA examination and intraoperative transoesophageal echocardiography might be helpful to avoid this complication.

Hydrogen sulfide alleviates mitochondrial damage and ferroptosis by regulating OPA3-NFS1 axis in doxorubicin-induced cardiotoxicity.

Ferroptosis is a major cause of cardiotoxicity induced by doxorubicin (DOX). Previous studies have shown that hydrogen sulfide (H2S) inhibits ferroptosis in cardiomyocytes and myoblasts, but the underlying mechanism has not been fully elucidated. In this study, we investigated the role of H2S in protecting against DOX-induced cardiotoxicity both in vivo and in vitro, and elucidated the potential mechanisms involved. We found that DOX downregulated the expression of glutathione peroxidase 4 (GPX4) and NFS1, and upregulated the expression of acyl-coenzyme A synthetase long-chain family member 4 (ACSL4) expression level, resulting in increased lipid peroxidation and ferroptosis. Additionally, DOX inhibited MFN2 expression and increased DRP1 and FIS1 expression, leading to abnormal mitochondrial structure and function. In contrast, exogenous H2S inhibited DOX-induced ferroptosis by restoring GPX4 and NFS1 expression, and reducing lipid peroxidation in H9C2 cells. This effect was similar to that of the ferroptosis antagonist ferrostatin-1 (Fer-1) in protecting against DOX-induced cardiotoxicity. We further demonstrated that the protective effect of H2S was mediated by the key mitochondrial membrane protein optic atrophy 3 (OPA3), which was downregulated by DOX and restored by exogenous H2S. Overexpression of OPA3 alleviated DOX-induced mitochondrial dysfunction and ferroptosis both in vivo and in vitro. Mechanistically, NFS1 has an inhibitory effect on ferroptosis, and NFS1 deficiency increases the susceptibility of cardiomyocytes to ferroptosis. OPA3 is involved in the regulation of ferroptosis by interacting with NFS1. Post-translationally, DOX promoted OPA3 ubiquitination, while exogenous H2S antagonized OPA3 ubiquitination by promoting OPA3 s-sulfhydration. In summary, our findings suggested that H2S protects against DOX-induced cardiotoxicity by inhibiting ferroptosis via targeting the OPA3-NFS1 axis. This provides a potential therapeutic strategy for the treatment of DOX-induced cardiotoxicity.

The Balance between the Left and Right Ventricular Deformation Evaluated by Speckle Tracking Echocardiography Is a Great Predictor of the Major Adverse Cardiac Event in Patients with Pulmonary Hypertension.

Cardiovascular failure is one of the most relevant causes of death in pulmonary hypertension (PH). With progressive increases of right ventricular (RV) afterload in PH patients, both RV and left ventricular (LV) function impair and RV-LV dyssynchrony develop in parallel. We aimed to analyze the balance between the left and right ventricular deformation to assess the outcome of patients with pulmonary hypertension by means of speckle tracking echocardiography. In this prospective study, 54 patients with invasively diagnosed pulmonary hypertension, and 26 healthy volunteers were included and underwent a broad panel of noninvasive assessment including 2D-echocardiography, 2D speckle tracking, 6-minute walking test and BNP. Patients were followed up for 338.7 ± 131.1 (range 60 to 572) days. There were significant differences in |LVGLS/RVFLS-1| and |LASc/RASc-1| between PH patients and the control group. During the follow up, 13 patients experienced MACEs, which included 7 patients with cardiac death and 6 patients with re-admitted hospital due to right ventricular dysfunction. In the multivariate Cox model analysis, |LVGLS/RVFLS-1| remained independent prognosis of markers (HR = 4.03). Our study findings show that |LVGLS/RVFLS-1| is of high clinical and prognostic relevance in pulmonary hypertension patients and reveal the importance of the balance between the left and right ventricular deformation.

Risk of device-related thrombosis following short-term oral anticoagulation with low-dose dabigatran versus warfarin after Watchman left atrial appendage occlusion.

BACKGROUND: Percutaneous left atrial appendage occlusion (LAAO) provides an alternative for poor candidates for long-term oral anticoagulation (OAC). To prevent device-related thrombosis (DRT), OAC should be continued for the first 45 days to allow complete endothelialization post-LAAO implantation. Whereas, evidence is limited on the feasibility and safety of direct oral anticoagulants (DOACs) used after LAAO. METHODS: This was a retrospective observational single-center study of AF patients undergoing LAAO with a Watchman device and receiving either low-dose dabigatran (110mg twice daily) or warfarin in the peri- and post-procedural period for 45 days. Transesophageal echocardiography was scheduled to perform at 6 weeks, 6 months, and 12 months after the procedure to assess the stability of the device and to detect DRT. Incidence of thromboembolic and bleeding events were also evaluated during the follow-up period. RESULTS: There were a total of 84 patients who successfully underwent Watchman implantation, with 38 patients (45.2%) receiving low-dose dabigatran and 46 patients (54.8%) using warfarin post-LAAO. Peri-procedural complications occurred in 10 patients, with 3 patients in the dabigatran group and 7 patients in the warfarin group (7.9% vs. 15.2%, p = 0.30). During the 12-month follow-up, 1 patient experienced major bleeding and 16 patients suffered minor bleeding in the warfarin group, while 5 patients treated with dabigatran had minor bleeding (34.8% vs. 13.2%, p = 0.02). Besides, 6 DRT (15.8%) were detected in dabigatran groups, and the incidence was higher than in the warfarin group (15.8% vs. 2.2%, p = 0.03). No DRT-related ischemic events were found. CONCLUSIONS: This study suggested that short-term low-dose dabigatran (110 mg twice daily) could significantly decrease the risk of bleeding compared with warfarin at the expense of increased risk of DRT post-LAAO. Therefore, low-dose dabigatran should be used with caution for post-implant anticoagulation of LAAO. Further studies are urgently needed on the feasibility and safety of DOACs post-LAAO.

Study of effects of anthracycline drugs on myocardial function in breast cancer patients by quantitative analysis of layer-specific strain via 2D-STI technology.

OBJECTIVE: This study aimed to explore the value of layer-specific strain analysis by two-dimensional speckle tracking imaging (2D-STI) in the assessment of myocardial toxicity in breast cancer patients receiving anthracycline chemotherapy. METHODS: Thirty-four breast cancer patients receiving anthracycline chemotherapy were prospectively enrolled. Conventional echocardiography and 2D-STI were evaluated at baseline after the third and sixth cycles of anthracycline chemotherapy. The strains of different layers of left ventricle (LV) including peak systolic longitudinal strain (endo-LS, mid-LS, epi-LS) and circumferential strain (endo-CS, mid-CS, epi-CS) were measured using EchoPAC analysis software. Peak systolic longitudinal strain (MV-LS, PM-LS, AP-LS), circumferential strain (MV-CS, PM-CS, AP-CS) and radial strain (MV-RS, PM-RS, AP-RS) were measured at mitral valve, papillary muscle and apex levels of LV respectively. Global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and left ventricular twist (LVtw) were also analyzed. RESULTS: There was no significant difference in the structural and functional parameters of conventional 2D echocardiography in different cycles of anthracycline chemotherapy (P>0.05); layer specific LS and CS in various cycles decreased layer by layer from inside to outside. LS and CS increased from basal segment to apical segment, while RS showed no obvious gradient characteristics; compared with baseline, GLS and LSs (endo-PM, endo-AP, mid-PM, mid-AP and epi-AP) of LV decreased significantly after the third cycle of chemotherapy (P<0.05); LSs (epi-MV and epi-AP) decreased significantly after the sixth cycle of chemotherapy (P<0.05). No significant changes were detected in layer specific CS, RS and LVtw (P>0.05). CONCLUSION: Layer-specific strain analysis by 2D-STI technology can quantitatively analyze global and regional functions of LV. The myocardial toxicity due to anthracycline chemotherapy can be detected by layer-specific LS of LV in early stage, which is great valuable to guiding clinical early intervention and improving prognosis.

Rationale and design of a prospective multi-center randomized trial of EARLY treatment by rivaroxaban versus warfarin in ST-segment elevation MYOcardial infarction with Left Ventricular Thrombus (EARLY-MYO-LVT trial).

BACKGROUND: Left ventricular thrombus (LVT), a common complication of acute ST-segment elevation myocardial infarction (STEMI), is associated with increased risk of systemic embolism and high mortality. Current STEMI guidelines recommend adding anticoagulant therapy to dual antiplatelet therapy (DAPT) if early-formulated LVT were detected, for which vitamin K antagonist (VKA) is the standard anticoagulant agent. The role of non-VKA oral anticoagulants (NOACs) in this scenario is uncertain. METHODS: The EARLY-MYO-LVT study will be a prospective, multi-center and randomized trial designed to investigate the efficacy and safety of rivaroxaban versus warfarin in the treatment of post-STEMI LVT. It will enroll 280 patients with STEMI who have developed LVT within the first month of symptom onset. They will be randomized at 1:1 ratio into the group of rivaroxaban 15 mg daily or VKA treatment (with targeted INR 2-2.5) on the basis of standard DAPT (100 mg daily aspirin plus 75 mg daily clopidogrel) for 3-6 months. The primary efficacy endpoint will be the probability of LVT resolution after 3-month triple therapy, and the principal safety outcome will be the incidence of major bleeding events during the treatment. DISCUSSION: The described study will systemically assess the efficacy and safety of NOACs-based anticoagulant therapy in the treatment of LVT subsequent to STEMI. TRIAL REGISTRATION: The EARLY-MYO-LVT trial (Clinical trial number: NCT03764241).

Initial anticoagulation experience with standard-dose rivaroxaban after Watchman left atrial appendage occlusion.

BACKGROUND: Warfarin is now recommended as the standard anti-thrombotic regimen to allow complete endothelialization over the Watchman device post percutaneous left atrial appendage occlusion (LAAO). However, the need for frequent monitoring, narrow therapeutic range, dietary restrictions and multiple drug interactions associated with warfarin have contributed to increasing uptake of non-vitamin K oral anticoagulants (NOACs) worldwide. At present, the feasibility and safety of NOACs instead of warfarin post-LAAO is lacking. METHODS: Patients who underwent successful Watchman device implantation between October 1, 2016 and September 30, 2017 were enrolled in a retrospective database. And only patients who received rivaroxaban in the periprocedural period were included in this study. Transesophageal echocardiography (TEE) follow-up was scheduled at 6 weeks, at 6 months, and at 12 months post-implantation to detect device-related thrombosis (DRT) or peri-device leak. Meanwhile, thromboembolic and bleeding events were also evaluated at the time of follow-up. RESULTS: Totally, 57 Watchman devices were successfully implanted and 10 patients who were allocated to rivaroxaban at the dosage of 20 mg once daily were included. During the follow-up, none of the patients using rivaroxaban experienced DRT, peri-device leak, thromboembolic complications and major bleeding events, except for 2 patients who suffered minor bleeding during the 6 weeks follow-up. CONCLUSIONS: This study suggests that a short course of standard-dose rivaroxaban following Watchman LAAO is associated with low incidence of thrombotic complications and bleeding events, and might be a feasible alternative regimen in Chinese. Further randomized trials and large sample of real-world studies are needed to validate our finding.

Novel application of quantitative flow ratio for predicting microvascular dysfunction after ST-segment-elevation myocardial infarction.

OBJECTIVES: This study evaluated quantitative flow ratio (QFR) to predict microvascular dysfunction (MVD) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: QFR is a novel approach for the rapid computation of fractional flow reserve based on three-dimensional quantitative coronary angiography. We hypothesized that QFR computation could be used to predict MVD after STEMI. METHODS: Indexes such as contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and hyperemic flow velocity (HFV) were calculated in 130 STEMI patients with culprit lesion with ≥50% diameter stenosis and TIMI flow grade 2/3 in the spontaneously recanalized culprit artery on initial angiography. MVD was defined as microvascular obstruction determined by contrast-enhanced cardiac magnetic resonance at a median of 5 days after percutaneous coronary intervention. RESULTS: Patients were divided into the MVD group (76/130, 58.5%) and non-MVD group (54/130, 41.5%). Patients with MVD had higher cQFR-fQFR value (0.080 ± 0.058 vs. 0.038 ± 0.039, p < .001) and lower modeled HFV (0.096 ± 0.044 vs. 0.144 ± 0.041 m/s, p < .001). Receiver operator characteristic curve analysis revealed that both the cQFR-fQFR value (area under the curve, AUC = 0.716, p < .001) and modeled HFV (AUC = 0.805, p < .001) had high specificity and positive predictive value to predict MVD. In multivariable logistic analysis, cQFR-fQFR was identified as an independent predictor of MVD (odds ratio = 9.800, p < .001). CONCLUSIONS: This proof-of-concept study suggested that QFR computation may be a useful tool to predict MVD after STEMI (Trial Registration:NCT03780335).

Device Sizing Guided by Echocardiography-Based Three-Dimensional Printing Is Associated with Superior Outcome after Percutaneous Left Atrial Appendage Occlusion.

BACKGROUND: Left atrial appendage (LAA) occlusion is an alternative to anticoagulation for stroke prevention in patients with atrial fibrillation. Accurate device sizing is crucial for optimal outcome. Patient-specific LAA models can be created using three-dimensional (3D) printing from 3D transesophageal echocardiographic (TEE) images, allowing in vitro model testing for device selection. The aims of this study were to assess the association of model-based device selection with procedural safety and efficacy and to determine if preprocedural model testing leads to superior outcomes. METHODS: In 72 patients who underwent imaging-guided LAA occlusion, 3D models of the LAA were created from 3D TEE data sets retrospectively (retrospective cohort). The optimal device determined by in vitro model testing was compared with the actual device used. Associations of model-match and model-mismatch device sizing with outcomes were analyzed. In another 32 patients, device selection was prospectively guided by 3D models in adjunct to imaging (prospective cohort). The impact of model-based sizing on outcomes was assessed by comparing the two cohorts. RESULTS: Patients in the retrospective cohort with model-mismatch sizing had longer procedure times, more implantation failures, more devices used per procedure, more procedural complications, more peridevice leak, more device thrombus, and higher cumulative incidence rates of ischemic stroke and cardiovascular or unexplained death (P < .05 for all) over 3.0 ± 2.3 years after LAA occlusion. Compared with the retrospective imaging-guided cohort, the prospective model-guided patients achieved higher implantation success and shorter procedural times (P < .05) without complications. Clinical device compression (r = 0.92) and protrusion (r = 0.95) agreed highly with model testing (P < .0001). Predictors for sizing mismatch were nonwindsock morphology (odds ratio, 4.7) and prominent LAA trabeculations (odds ratio, 7.1). CONCLUSIONS: In patients undergoing LAA occlusion, device size selection in agreement with 3D-printed model-based sizing is associated with improved safety and efficacy. Preprocedural device sizing with 3D models in adjunct to imaging guidance may lead to superior outcomes.

Assessment of left atrial remodeling in paroxysmal atrial fibrillation with speckle tracking echocardiography: a study with an electrophysiological mapping system.

This study aimed to evaluate left atrial (LA) remodeling and fibrosis in paroxysmal atrial fibrillation (AF) using speckle tracking echocardiography (STE) based on the findings with radiofrequency catheter ablation (RFCA) so as to predict atrial remodeling prior to ablation. A total of 40 patients with paroxysmal AF were enrolled and divided into two groups based on LA bipolar voltage detected during RFCA: those with low-voltage zone (LVZ) (LV group, n = 19) and those without LVZ (non-LV group, n = 21). The segmental and global LA reservoir, conduit and contractile strain (εs, εe, εa) were analyzed using two-dimensional STE before RFCA. The segmental and global εs, εe, εa (%) decreased in the LV group. Especially, the εs in anteroseptal upper (18.32 ± 7.94 vs. 31.61 ± 9.39) and lower segments (16.60 ± 7.23 vs. 29.23 ± 9.81), posteroseptal upper (22.24 ± 6.65 vs. 32.23 ± 10.57) and lower segments (18.24 ± 6.49 vs. 26.40 ± 7.12), and the global εs (23.85 ± 6.74 vs. 30.48 ± 8.67) significantly decreased in the LV group than in the non-LV group (all P < 0.05). The εs ≤ 24.07 in the anteroseptal upper segment was an effective parameter to differentiate the LV group (sensitivity, 84%; specificity, 81%, P < 0.001). Besides, global εs tended to be an independent determinant of the LVZ (odds ratio 1.347, P = 0.046). STE enables a noninvasive method to evaluate LA remodeling prior ablation.

Prevalence and Prognosis of Portopulmonary Hypertension in 223 Liver Transplant Recipients.

Objective: To investigate the prevalence and prognosis of portopulmonary hypertension (PoPH) in liver transplant recipients. Methods: Patients with advanced liver disease who underwent orthotopic liver transplantation (OLT) were included in this retrospective study from January 2012 to June 2015. According to the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines for the diagnosis of pulmonary hypertension (PH), patients with tricuspid regurgitation velocity (TRV) >3.4 m/s or 2.9 m/s ≤ TRV ≤ 3.4 m/s coexisting with other echocardiographic PH signs were judged as PH. PH patients with portal hypertension and without other known causes of PH were diagnosed as PoPH. Results: A total of 223 (170 males and 53 females) middle-aged (50.9 ± 9 years old) liver transplant recipients were included in this study. Fourteen patients (6.3%) were diagnosed with PoPH, and none of the patients were treated with vasodilators before or after OLT. After OLT, patients were followed up for 26 ± 13.5 months. In total, 8 of 14 (57%) PoPH patients died, and the main cause of death was pulmonary infection. Kaplan-Meier survival curves revealed a significant difference in survival between PoPH and non-PoPH patients (p < 0.001), and the median survival time after OLT of PoPH was 11.4 months. Conclusions: The prevalence of PoPH was 6.3% in OLT recipients. The survival of untreated PoPH patients was dismal after OLT.

Ascending Aortic Strain Analysis Using 2-Dimensional Speckle Tracking Echocardiography Improves the Diagnostics for Coronary Artery Stenosis in Patients With Suspected Stable Angina Pectoris.

BACKGROUND: Arterial stiffening and atherosclerosis tend to coexist. Strain imaging, using a 2-dimensional speckle tracking (2D-ST) method, has been used for arterial stiffness assessment and early identification of atherosclerosis. We investigated whether the ascending aortic strain assessed by 2D-ST echocardiography at rest can predict the presence of coronary artery disease (CAD). METHODS AND RESULTS: Two hundred seventy-one consecutive patients with suspected stable angina pectoris sequentially underwent exercise treadmill testing, 2-dimensional echocardiography, M-mode echocardiography, 2D-ST echocardiography, and coronary angiography. Circumferential ascending aortic strain (CAAS) and radial ascending aortic strain were assessed by 2D-ST echocardiography. Ninety-two patients with coronary lumen area stenosis ≥70% were categorized as having significant CAD. Global CAAS was significantly lower in patients with significant CAD (7.41±2.30% versus 11.54±4.03%; P<0.001) and remained an independent predictor of significant CAD (odds ratio, 0.64 [0.54-0.75]; P<0.001) after multivariate regression. Based on the receiver operating characteristic curve for diagnosing significant CAD, the optimal cut-off value of global CAAS was ≤9.22% (sensitivity, 86%; specificity, 70%; area under curve=0.82; P<0.001). Global CAAS decreased with increasing severity of CAD and was significantly associated with 3-vessel disease (odds ratio, 0.58 [0.42-0.79]; P<0.001). Diagnostics for significant CAD were remarkably better for global CAAS combined with exercise treadmill testing than for exercise treadmill testing alone (area under curve=0.88 versus 0.78; P<0.001). CONCLUSIONS: Global CAAS assessed by 2D-ST echocardiography at rest was able to predict the presence of significant CAD and identify multivessel disease. In addition, global CAAS combined with exercise treadmill testing remarkably improved the diagnostics for significant CAD.

Combined use of external therapeutic ultrasound and tirofiban has synergistic therapeutic effects on no-reflow after myocardial reperfusion.

OBJECTIVE: This study aimed to evaluate the effects of the combined use of external therapeutic ultrasound (ETUS) and the specific glycoprotein IIb/IIIa inhibitor tirofiban on myocardial no-reflow in a canine model of acute myocardial infarction after reperfusion. METHODS: The canine myocardial no-reflow model was established by a 3-hour occlusion of the left anterior desecending coronary artery followed by a 2-hour reperfusion. Twenty-four canines were divided into four groups (6/group): (1) control, (2) tirofiban alone, (3) ETUS combined with tirofiban (ETUS + tirofiban), and (4) ETUS alone. RESULTS: The area of no-reflow in each of the three treatment groups was significantly decreased, compared with the control group, with the ETUS + tirofiban group having the smallest area. Also, the ETUS + tirofiban group had the highest recanalized rate of microvessels in the no-reflow area and fewer impaired cellular organelles. The recovery rates of the endocardial and middle circumferential strain as well as longitudinal strain in the ETUS + tirofiban group were significantly greater than those of the tirofiban group. Moreover, the expression of hypoxia-inducible factor-1α (HIF-1α) was significantly increased in the ETUS + tirofiban group, compared with the other groups. CONCLUSIONS: The combined use of ETUS and tirofiban offers synergistic benefits for the treatment of myocardial no-reflow.

Optimal nonvitamin K antagonist oral anticoagulant therapy in a warfarin-sensitive patient after left atrial appendage closure: A case report.

RATIONALE: Developing an optimal medication strategy poses a challenging task in fragile patients after left atrial appendage closure (LAAC). We report an optimal nonvitamin K antagonist oral anticoagulant (NOAC) therapy in a warfarin-sensitive patient after LAAC. PATIENT CONCERNS: A 77-year-old nonvalvular atrial fibrillation (NVAF) male carrying 2 warfarin-sensitive alleles experienced 2 gum-bleeding with the international normalized ratio (INR) around 3. DIAGNOSES: Persistent NVAF with a history of subtotal gastrectomy and moderate renal insufficiency. INTERVENTIONS: Warfarin was discontinued and vitamin K1 was immediately administrated via intravenous infusion. LAAC was regarded as a preferable option, and rivaroxaban 15 mg daily was managed after LACC. OUTCOMES: Complete endothelialization on the surface of device was detected via transoesophageal echocardiography (TEE), and no peridevice spillage and adverse event occurred. LESSONS: A post-LAAC treatment with NOAC may be a viable regimen in patients intolerant to warfarin.

Assessment of Subclinical Doxorubicin-induced Cardiotoxicity in a Rat Model by Speckle-Tracking Imaging / Avaliação de Cardiotoxicidade Subclínica Induzida por Doxorrubicina em um Modelo de Rato por Speckle-Tracking

Abstract Backgrounds: Despite their clear therapeutic benefits, anthracycline-induced cardiotoxicity is a major concern limiting the ability to reduce morbidity and mortality associated with cancers. The early identification of anthracycline-induced cardiotoxicity is of vital importance to assess the cardiac risk against the potential cancer treatment. Objective: To investigate whether speckle-tracking analysis can provide a sensitive and accurate measurement when detecting doxorubicin-induced left ventricular injury. Methods: Wistar rats were divided into 4 groups with 8 rats each, given doxorubicin intraperitoneally at weekly intervals for up to 4 weeks. Group 1: 2.5 mg/kg/week; group 2: 3 mg/kg/week; group 3: 3.5mg/kg/week; group 4: 4mg/kg/week. An additional 5 rats were used as controls. Echocardiographic images were obtained at baseline and 1 week after the last dose of treatment. Radial (Srad) and circumferential (Scirc) strains, radial (SRrad) and circumferential (SRcirc) strain rates were analyzed. After the experiment, cardiac troponin I (cTnI) was analyzed and the heart samples were histologically evaluated. Results: After doxorubicin exposure, LVEF was significantly reduced in group 4 (p = 0.006), but remained stable in the other groups. However, after treatment, Srads were reduced in groups 2, 3 and 4 (p all < 0.05). The decrease in Srads was correlated with cTnI (rho = -0.736, p = 0.000) and cardiomyopathy scores (rho = -0.797, p = 0.000). Conclusion: Radial strain could provide a sensitive and noninvasive index in early detection of doxorubicin-induced myocardial injury. The changes in radial strain had a significant correlation with myocardial lesions and serum cardiac troponin I levels, indicating that this parameter could accurately evaluate cardiotoxicity severity.

Resumo Fundamento: Apesar dos seus claros benefícios terapêuticos, a cardiotoxicidade induzida pela antraciclina é uma grande preocupação que limita a capacidade de reduzir a morbidade e mortalidade associadas com cânceres. A identificação precoce da cardiotoxicidade induzida por antraciclina é de vital importância para o equilíbrio entre o risco cardíaco e o potencial tratamento do câncer. Objetivo: Investigar se a análise por speckle-tracking pode fornecer uma medida sensível e precisa na detecção de lesão ventricular esquerda induzida por doxorrubicina. Métodos: Ratos Wistar foram divididos em 4 grupos de 8 ratos cada, e doxorrubicina foi administrada intraperitonealmente em intervalos semanais de até 4 semanas. Grupo 1: 2,5 mg/kg/semana; Grupo 2: 3 mg/kg/semana; Grupo 3: 3,5 mg/kg/semana; Grupo 4: 4 mg/kg/semana. Foram utilizados 5 ratos adicionais como controles. As imagens ecocardiográficas foram obtidas na linha basal e 1 semana após a última dose do tratamento. Foram analisados o strain radial (Srad) e circunferencial (Scirc) e as taxas de strain radial (TSrad) e circunferencial (TScirc). Após o experimento, a troponina cardíaca I (cTnI) foi analisada e as amostras cardíacas foram avaliadas histologicamente. Resultados: Após a exposição à doxorrubicina, a FEVE foi significativamente reduzida no grupo 4 (p = 0,006), mas permaneceu estável nos outros grupos. Entretanto, após o tratamento, os Srads foram reduzidos nos grupos 2, 3 e 4 (p < 0,05). A diminuição dos Srads foi correlacionada com cTnI (rho = -0,736, p = 0,000) e os escores de cardiomiopatia (rho = -0,797, p = 0,000). Conclusão: O strain radial pode fornecer um índice sensível e não-invasivo na detecção precoce da lesão miocárdica induzida pela doxorrubicina. As alterações do strain radial apresentaram correlação significativa com lesões miocárdicas e níveis séricos de troponina I cardíaca, indicando que esse parâmetro pode avaliar com precisão a gravidade da cardiotoxicidade.

Assessment of Subclinical Doxorubicin-induced Cardiotoxicity in a Rat Model by Speckle-Tracking Imaging.

BACKGROUNDS:: Despite their clear therapeutic benefits, anthracycline-induced cardiotoxicity is a major concern limiting the ability to reduce morbidity and mortality associated with cancers. The early identification of anthracycline-induced cardiotoxicity is of vital importance to assess the cardiac risk against the potential cancer treatment. OBJECTIVE:: To investigate whether speckle-tracking analysis can provide a sensitive and accurate measurement when detecting doxorubicin-induced left ventricular injury. METHODS:: Wistar rats were divided into 4 groups with 8 rats each, given doxorubicin intraperitoneally at weekly intervals for up to 4 weeks. Group 1: 2.5 mg/kg/week; group 2: 3 mg/kg/week; group 3: 3.5mg/kg/week; group 4: 4mg/kg/week. An additional 5 rats were used as controls. Echocardiographic images were obtained at baseline and 1 week after the last dose of treatment. Radial (Srad) and circumferential (Scirc) strains, radial (SRrad) and circumferential (SRcirc) strain rates were analyzed. After the experiment, cardiac troponin I (cTnI) was analyzed and the heart samples were histologically evaluated. RESULTS:: After doxorubicin exposure, LVEF was significantly reduced in group 4 (p = 0.006), but remained stable in the other groups. However, after treatment, Srads were reduced in groups 2, 3 and 4 (p all < 0.05). The decrease in Srads was correlated with cTnI (rho = -0.736, p = 0.000) and cardiomyopathy scores (rho = -0.797, p = 0.000). CONCLUSION:: Radial strain could provide a sensitive and noninvasive index in early detection of doxorubicin-induced myocardial injury. The changes in radial strain had a significant correlation with myocardial lesions and serum cardiac troponin I levels, indicating that this parameter could accurately evaluate cardiotoxicity severity. FUNDAMENTO:: Apesar dos seus claros benefícios terapêuticos, a cardiotoxicidade induzida pela antraciclina é uma grande preocupação que limita a capacidade de reduzir a morbidade e mortalidade associadas com cânceres. A identificação precoce da cardiotoxicidade induzida por antraciclina é de vital importância para o equilíbrio entre o risco cardíaco e o potencial tratamento do câncer. OBJETIVO:: Investigar se a análise por speckle-tracking pode fornecer uma medida sensível e precisa na detecção de lesão ventricular esquerda induzida por doxorrubicina. MÉTODOS:: Ratos Wistar foram divididos em 4 grupos de 8 ratos cada, e doxorrubicina foi administrada intraperitonealmente em intervalos semanais de até 4 semanas. Grupo 1: 2,5 mg/kg/semana; Grupo 2: 3 mg/kg/semana; Grupo 3: 3,5 mg/kg/semana; Grupo 4: 4 mg/kg/semana. Foram utilizados 5 ratos adicionais como controles. As imagens ecocardiográficas foram obtidas na linha basal e 1 semana após a última dose do tratamento. Foram analisados o strain radial (Srad) e circunferencial (Scirc) e as taxas de strain radial (TSrad) e circunferencial (TScirc). Após o experimento, a troponina cardíaca I (cTnI) foi analisada e as amostras cardíacas foram avaliadas histologicamente. RESULTADOS:: Após a exposição à doxorrubicina, a FEVE foi significativamente reduzida no grupo 4 (p = 0,006), mas permaneceu estável nos outros grupos. Entretanto, após o tratamento, os Srads foram reduzidos nos grupos 2, 3 e 4 (p < 0,05). A diminuição dos Srads foi correlacionada com cTnI (rho = -0,736, p = 0,000) e os escores de cardiomiopatia (rho = -0,797, p = 0,000). CONCLUSÃO:: O strain radial pode fornecer um índice sensível e não-invasivo na detecção precoce da lesão miocárdica induzida pela doxorrubicina. As alterações do strain radial apresentaram correlação significativa com lesões miocárdicas e níveis séricos de troponina I cardíaca, indicando que esse parâmetro pode avaliar com precisão a gravidade da cardiotoxicidade.

Impact of Intramyocardial Hemorrhage and Microvascular Obstruction on Cardiac Mechanics in Reperfusion Injury: A Speckle-Tracking Echocardiographic Study.

BACKGROUND: Intramyocardial hemorrhage (IMH) and microvascular obstruction (MVO) are two major mechanisms of reperfusion injury of the left ventricle after acute ST-segment elevation myocardial infarction (STEMI). The aim of this study was to assess the impact of IMH and MVO on left ventricular (LV) cardiac mechanics using two-dimensional speckle-tracking echocardiography during the acute phase of STEMI and on LV functional recovery. METHODS: Eighty-one patients with STEMI who received primary reperfusion therapy were prospectively studied. Infarct segments were classified by cardiac magnetic resonance according to infarct transmurality and the presence or absence of IMH and/or MVO. Segmental systolic longitudinal strain, circumferential strain (CS), and radial strain were measured by two-dimensional speckle-tracking echocardiography. Adverse LV remodeling and major adverse cardiovascular events were assessed at 1 year. RESULTS: MVO without IMH was much less frequent in nontransmural infarct segments than in transmural infarct segments (6.0% vs 19.1%, P = .000), while IMH was present only in transmural infarct segments. In nontransmural infarct segments, MVO was not associated with any significant changes in strain (P > .5). In transmural infarct segments, there were no differences in all types of strain between segments without reperfusion injury and those with MVO alone (P > .20). IMH was evident in the midmyocardial layer within the infarct zone in 196 segments (46.1%). The presence of IMH in addition to MVO decreased CS significantly (P = .004), but not longitudinal and radial strain (P > .5). A receiver operating characteristic curve analysis with cross-validation by k-folding showed that the sensitivity and specificity of CS using a cutoff of >-11.66% to diagnose IMH were 78.00% and 79.45%, respectively (area under the curve = 0.86; P = .0001). At 1 year, patients with major adverse cardiovascular events and LV remodeling had significantly lower baseline measurements of all types of global strain (P < .05). CONCLUSIONS: In the acute phase of STEMI, reperfusion MVO and IMH injury have differential effects on cardiac mechanics. IMH preferentially affects CS, presumably related to its location in the midmyocardial layer.

YiXin-Shu, a ShengMai-San-based traditional Chinese medicine formula, attenuates myocardial ischemia/reperfusion injury by suppressing mitochondrial mediated apoptosis and upregulating liver-X-receptor α.

Positive evidence from clinical trials has fueled growing acceptance of traditional Chinese medicine (TCM) for the treatment of cardiac diseases; however, little is known about the underlying mechanisms. Here, we investigated the nature and underlying mechanisms of the effects of YiXin-Shu (YXS), an antioxidant-enriched TCM formula, on myocardial ischemia/reperfusion (MI/R) injury. YXS pretreatment significantly reduced infarct size and improved viable myocardium metabolism and cardiac function in hypercholesterolemic mice. Mechanistically, YXS attenuated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway (as reflected by inhibition of mitochondrial swelling, cytochrome c release and caspase-9 activity, and normalization of Bcl-2 and Bax levels) without altering the death receptor and endoplasmic reticulum-stress death pathways. Moreover, YXS reduced oxidative/nitrative stress (as reflected by decreased superoxide and nitrotyrosine content and normalized pro- and anti-oxidant enzyme levels). Interestingly, YXS upregulated endogenous nuclear receptors including LXRα, PPARα, PPARß and ERα, and in-vivo knockdown of cardiac-specific LXRα significantly blunted the cardio-protective effects of YXS. Collectively, these data show that YXS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and oxidative stress and by upregulating LXRα, thereby providing a rationale for future clinical trials and clinical applications.