Long-term outcomes of left atrial appendage occlusion in patients with atrial fibrillation and end stage renal disease.

OBJECTIVE: In patients with atrial fibrillation (AF) and end-stage renal disease (ESRD), oral anticoagulants are contraindicated, and left atrial appendage occlusion (LAAO) is an alternative treatment. However, the efficacy of thromboembolic prevention using LAAO in these patients has rarely been reported in Asian populations. To our knowledge, this is the first long-term LAAO study in patients with AF undergoing dialysis in Asia. METHODS: In this study, 310 patients (179 men) with a mean age of 71.3 ± 9.6 years and mean CHA2DS2-VASc 4.2 ± 1.8 were consecutively enrolled at multiple centers in Taiwan. The outcomes of 29 patients with AF and ESRD undergoing dialysis who underwent LAAO were compared to those without ESRD. The primary composite outcomes were stroke, systemic embolization, or death. RESULTS: No difference in mean CHADS-VASc score was noted between patients with versus without ESRD (4.1 ± 1.8 vs. 4.6 ± 1.9, p = 0.453). After a mean follow-up of 38 ± 16 months, the composite endpoint was significantly higher in patients with ESRD (hazard ratio, 5.12 [1.4-18.6]; p = 0.013) than in those without ESRD after LAAO therapy. Mortality was also higher in patients with ESRD (hazard ratio, 6.6 [1.1-39.7]; p = 0.038). The stroke rate was numerically higher in patients with versus without ESRD, but the difference was not statistically significant (hazard ratio, 3.2 [0.6-17.7]; p = 0.183). Additionally, ESRD was associated with device-related thrombosis (odds ratio, 6.15; p = 0.047). CONCLUSION: Long-term outcomes of LAAO therapy may be less favorable in patients with AF undergoing dialysis, possibly because of the poor condition of patients with ESRD.

Enhancement of bicycle exercise capacity in patients with chronotropic incompetence through closed-loop stimulation: a randomized crossover trial.

AIMS: This study aimed to investigate the effectiveness of closed-loop stimulation (CLS) pacing compared with the traditional DDD mode in patients with chronotropic incompetence (CI) using bicycle-based cardiopulmonary exercise testing (CPET). METHODS AND RESULTS: This single-centre, randomized crossover trial involved 40 patients with CI. Patients were randomized to receive either DDD-CLS or DDD mode pacing for 2 months, followed by a crossover to the alternative mode for an additional 2 months. Bicycling-based CPET was conducted at the 3- and 5-month follow-up visits to assess exercise capacity. Other cardiopulmonary exercise outcome measures and health-related quality of life (QoL) were also assessed. DDD-CLS mode pacing significantly improved exercise capacity, resulting in a peak oxygen uptake (14.8 ± 4.0 vs. 12.0 ± 3.6 mL/kg/min, P < 0.001) and oxygen uptake at the ventilatory threshold (10.0 ± 2.2 vs. 8.7 ± 1.8 mL/kg/min, P < 0.001) higher than those of the DDD mode. However, there were no significant differences in other cardiopulmonary exercise outcome measures such as ventilatory efficiency of carbon dioxide production slope, oxygen uptake efficiency slope, and end-tidal carbon dioxide between the two modes. Patients in the DDD-CLS group reported a better QoL, and 97.5% expressed a preference for the DDD-CLS mode. CONCLUSION: DDD-CLS mode pacing demonstrated improved exercise capacity and QoL in patients with CI, highlighting its potential as an effective pacing strategy for this patient population.

Use of the CHA2DS2-VASc score to predict subsequent myocardial infarction in atrial fibrillation.

BACKGROUND: The risk of subsequent myocardial infarction (MI) varies widely in patients with atrial fibrillation (AF). No convenient scoring system currently exists to identify MI in AF. While each element of the CHA2DS2-VASc (congestive heart failure; hypertension; age ≥75 years [doubled]; type 2 diabetes; previous stroke or thromboembolism [doubled]; vascular disease; age 65-75 years; and sex category) score can increase the likelihood of MI, this retrospective longitudinal study aimed to determine the accuracy of the CHA2DS2-VASc score in predicting subsequent MI risk in AF. METHODS: A total of 29,341 patients with AF were enrolled and followed up from January 2010 until the first occurrence of MI or until December 2020. The primary endpoint was the occurrence of subsequent MI. RESULTS: The average age of the study population was 71 years, and 43.2% were male. The mean CHA2DS2-VASc score was found to be higher in patients with AF who had experienced an MI than in those who had not (3.56 ± 1.92 vs. 3.32 ± 1.81, p < 0.001). During the long-term follow-up, the risk of subsequent MI increased by 22% with every one-point increase in the CHA2DS2-VASc score (hazard ratio 1.22, 95% confidence interval 1.19-1.25; p < 0.001). Kaplan-Meier analysis revealed that high CHA2DS2-VASc scores were more likely to experience an MI than those with low CHA2DS2-VASc scores (log-rank p < 0.001). Furthermore, the CHA2DS2-VASc score was a significant predictor of MI in multivariate regression analysis. CONCLUSION: The CHA2DS2-VASc score is a valuable predictor of subsequent MI risk in patients with AF.

Identification of Coronary Culprit Lesion in ST Elevation Myocardial Infarction by Using Deep Learning.

OBJECTIVE: Early revascularization of the occluded coronary artery in patients with ST elevation myocardial infarction (STEMI) has been demonstrated to decrease mortality and morbidity. Currently, physicians rely on features of electrocardiograms (ECGs) to identify the most likely location of coronary arteries related to an infarct. We sought to predict these culprit arteries more accurately by using deep learning. METHODS: A deep learning model with a convolutional neural network (CNN) that incorporated ECG signals was trained on 384 patients with STEMI who underwent primary percutaneous coronary intervention (PCI) at a medical center. The performances of various signal preprocessing methods (short-time Fourier transform [STFT] and continuous wavelet transform [CWT]) with different lengths of input ECG signals were compared. The sensitivity and specificity for predicting each infarct-related artery and the overall accuracy were evaluated. RESULTS: ECG signal preprocessing with STFT achieved fair overall prediction accuracy (79.3%). The sensitivity and specificity for predicting the left anterior descending artery (LAD) as the culprit vessel were 85.7% and 88.4%, respectively. The sensitivity and specificity for predicting the left circumflex artery (LCX) were 37% and 99%, respectively, and the sensitivity and specificity for predicting the right coronary artery (RCA) were 88.4% and 82.4%, respectively. Using CWT (Morlet wavelet) for signal preprocessing resulted in better overall accuracy (83.7%) compared with STFT preprocessing. The sensitivity and specificity were 93.46% and 80.39% for LAD, 56% and 99.7% for LCX, and 85.9% and 92.9% for RCA, respectively. CONCLUSION: Our study demonstrated that deep learning with a CNN could facilitate the identification of the culprit coronary artery in patients with STEMI. Preprocessing ECG signals with CWT was demonstrated to be superior to doing so with STFT.

Bailout left atrial appendage occluder for pulmonary vein isolation and electrical cardioversion in patients with atrial fibrillation and left atrial appendage thrombus: a pilot study.

BACKGROUND: Cardioversion and catheter-based circumferential pulmonary vein isolation (CPVI) are established rhythm control treatment strategies for patients with atrial fibrillation (AF). However, these treatments are contraindicated for AF patients with a left atrial appendage (LAA) thrombus. METHODS: We conducted the first-in-man case series study to evaluate the feasibility and safety of performing cardioversion or CPVI in AF patients with LAA thrombus immediately after implantation of LAA Occluder (LAAO) in a combined procedure. In our multi-center LAAO registry of 310 patients, 27 symptomatic and drug-refractory AF patients underwent a combined procedure of LAAO and CPVI, among whom 10 (mean age 68 ± 16 years, 6 men) having anticoagulant-resistant LAA thrombus received a bailout procedure of LAAO implantation first then CPVI, and the other 17 patients without LAA thrombus received CPVI first then LAAO for comparison. RESULTS: The mean CHA2DS2-VASc score and HAS-BLED score were comparable between these two groups. In patients with LAA thrombus, we put carotid filters and did a no-touch technique, neither advancing the wire and sheath into the LAA nor performing LAA angiography. After LAAO implantation, the connecting cable was still connected to the occluder when cardioversion was performed. During CPVI, the occluder location was registered in the LA geometry by three-dimensional mapping to guide the catheter not to touch the LAAO. The procedure was successful in all the patients without intra-procedural complications. After a mean follow-up of 1.7 ± 0.7 years, there was no device embolization, peri-device leak ≧ 5 mm or stroke event in both groups. The AF recurrence rate was also similar between the two groups (P = 0.697). CONCLUSION: We demonstrated that cardioversion or CPVI is doable in symptomatic AF patients with LAA thrombus if LAA was occluded ahead as a bailout procedure.

Peri-device leakage not CHA2DS2-VASc is associated with post-left atrial appendage closure cardiovascular event.

OBJECTIVE: In patients with non-valvular atrial fibrillation (NVAF), the left atrial appendage occluder (LAAO) is an alternative treatment for stroke prevention. However, thromboembolic event still occur, and the predictors are unknown. METHODS: The first Asian long-term follow-up study consisted of 308 patients with mean age 71.9±9.5 years, mean CHA2DS2-VASc 4.1 ± 1.8 since 2013. Primary outcome was defined as any type of ischemic stroke/transient ischemic attack (TIA), systemic embolization and cardiovascular death. RESULTS: There was no procedural-related TIA or stroke. After a mean follow-up of 38±16 months, the ischemic stroke/TIA rate was 1.9 and cardiovascular death rate 0.3 per 100 patient-year. The rate of peri-device leak (PDL) was 11.9% and device-related thrombus (DRT) 2.6%. In the multivariable analyses, PDL was the only independent predictor of stroke/TIA (hazard ratio 5.5, p=0.008). CHA2DS2-VASc score, prior history of stroke, DRT and post-procedural anti-thrombotic regimen/duration were not associated with outcomes. Implantation of Watchman was associated with PDL (odds ratio 4.35, p=0.001). CONCLUSIONS: PDL is the only independent predictor of post-LAAO stroke. The risk of stroke for patients with NVAF may be controllable after LAA is occluded, because PDL is preventable and treatable.

The Antihypertensive Effects and Safety of LCZ696 in Patients with Hypertension: A Systemic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The management of hypertension remains suboptimal throughout the world. METHODS: We performed a random-effects model meta-analysis of randomized controlled trials to determine the effectiveness and safety of sacubitril/valsartan (LCZ696) for the treatment of high arterial pressure. Relevant published articles from PubMed, Cochrane base, and Medline were examined, and the last search date was December 2020. Only published randomized controlled trials and double-blind studies were selected for further analysis. The mean reductions in systolic blood pressure (msSBP) and diastolic blood pressure (msDBP) in the sitting position, as well as the mean reductions in ambulatory systolic blood pressure (maSBP) and ambulatory diastolic blood pressure (maDBP), were assumed as efficacy endpoints. Adverse events (AEs) were considered as safety outcomes. RESULTS: Ten studies with a total of 5931patients were included for analysis. Compared with placebo, LCZ696 had a significant reduction in msSBP (weight mean difference (WMD) = -6.52 mmHg, 95% confidence interval (CI): -8.57 to -4.47; p < 0.001), msDBP (WMD = -3.32 mmHg, 95% CI: -4.57 to -2.07; p < 0.001), maSBP (WMD = -7.08 mmHg, 95% CI: -10.48 to -3.68; p < 0.001), maDBP (WMD = -3.28 mmHg, 95% CI: -4.55 to -2.02, p < 0.001). In subgroup analysis, only 200 mg and 400 mg LCZ696 showed a significant BP reduction. There was no difference in the AE rate between the LCZ696 and placebo groups (WMD = 1.02, 95% CI: 0.83 to 1.27, p = 0.54). Egger's test revealed a potential publication bias for msSBP (p = 0.025), but no publication bias for other outcomes. CONCLUSION: LCZ696 may reduce blood pressure more efficaciously than traditional therapy in hypertensive patients without increasing adverse effects.

Chrysin boosts KLF2 expression through suppression of endothelial cell-derived exosomal microRNA-92a in the model of atheroprotection.

PURPOSE: Atherosclerosis and its related clinical complications are the leading cause of death. MicroRNA (miR)-92a in the inflammatory endothelial dysfunction leads to atherosclerosis. Krüppel-like factor 2 (KLF2) is required for vascular integrity and endothelial function maintenance. Flavonoids possess many biological properties. This study investigated the vascular protective effects of chrysin in balloon-injured carotid arteries. MATERIALS AND METHODS: Exosomes were extracted from human coronary artery endothelial cell (HCAEC) culture media. Herb flavonoids and chrysin were the treatments in these atheroprotective models. Western blotting and real-time PCRs were performed. In situ hybridization, immunohistochemistry, and immunofluorescence analyses were employed. RESULTS: MiR-92a increased after balloon injury and was present in HCAEC culture media. Chrysin was treated, and significantly attenuated the miR-92a levels after balloon injury, and similar results were obtained in HCAEC cultures in vitro. Balloon injury-induced miR-92a expression, and attenuated KLF2 expression. Chrysin increased the KLF2 but reduced exosomal miR-92a secretion. The addition of chrysin and antagomir-92a, neointimal formation was reduced by 44.8 and 49.0% compared with balloon injury after 14 days, respectively. CONCLUSION: Chrysin upregulated KLF2 expression in atheroprotection and attenuated endothelial cell-derived miR-92a-containing exosomes. The suppressive effect of miR-92a suggests that chrysin plays an atheroprotective role. Proposed pathway for human coronary artery endothelial cell (HCAEC)-derived exosomes induced by chrysin to suppress microRNA (miR)-92a expression and counteract the inhibitory effect of miR-92a on KLF2 expression in HCAECs. This provides an outline of the critical role of the herbal flavonoid chrysin, which may serve as a valuable therapeutic supplement for atheroprotection.

Successful bailout stenting strategy against rare spontaneous retrograde dissection of partially absorbed magnesium-based resorbable scaffold: A case report.

BACKGROUND: In the development of coronary stent technology, bioresorbable scaffolds are promising milestones in improving the clinical treatment of coronary artery disease. The "leave nothing behind" motto is the premise of the fourth revolution in percutaneous coronary intervention (PCI). Studies proving the safety and efficacy of the magnesium-based resorbable scaffolds (MgBRSs) include the BIOSOLVE-I and BIOSOLVE-II trials and the latest BIOSOLVE-IV registry. However, spontaneous retrograde dissection of a partially absorbed MgBRS may still occur, albeit rarely. CASE SUMMARY: We describe an unusual case of coronary artery disease in a patient who had undergone a successful PCI 8 mo earlier, where an MgBRS was implanted into the left anterior descending artery (LAD) and left circumflex artery with drug-coated balloons for a ramus intermedius branch stenosis to achieve the "leave nothing behind" therapeutic intention and was currently presenting with a gradual worsening of chest tightness. The distal edge vascular response, during subsequent attempts with balloon angioplasty was performed smoothly. However, spontaneous retrograde dissection of a partially absorbed MgBRS in the LAD ensued. Successful bailout stenting was performed with revascularization of the entry and exit sites created by spontaneous dissection and complete sealing of the intramural hematoma. The patient recovered well and was discharged after 2 d of intervention. When followed up in August 2020 (7 mo later), the patient showed uneventful recovery. CONCLUSION: Spontaneous retrograde dissection of a partially absorbed MgBRS was successfully treated using bailout sirolimus-eluting coronary stent strategy.

Cyclic stretching boosts microRNA-499 to regulate Bcl-2 via microRNA-208a in atrial fibroblasts.

MicroRNAs that modulate transcription can regulate other microRNAs and are also up-regulated under pathological stress. MicroRNA-499 (miR-499), microRNA-208a (miR-208a) and B-cell lymphoma 2 (Bcl-2) play roles in cardiovascular diseases, such as direct reprogramming of cardiac fibroblast into cardiomyocyte and cardiomyocyte apoptosis. Whether miR208a, miR499 and Bcl-2 were critical regulators in cardiac fibroblast apoptosis under mechanical stretching conditions in human cardiac fibroblasts-adult atrial (HCF-aa) was investigated. Using negative pressure, HCF-aa grown on a flexible membrane base were cyclically stretched to 20% of their maximum elongation. In adult rats, an aortocaval shunt was used to create an in vivo model of volume overload. MiR208a was up-regulated early by stretching and returned to normal levels with longer stretching cycles, whereas the expression of miR499 and Bcl-2 was up-regulated by longer stretching times. Pre-treatment with antagomir-499 reversed the miR-208a down-regulation, whereas Bcl-2 expression could be suppressed by miR-208a overexpression. In the HCF-aa under stretching for 1 h, miR-499 overexpression decreased pri-miR-208a luciferase activity; this inhibition of pri-miR-208a luciferase activity with stretching was reversed when the miR-499-5p binding site in pri-miR-208a was mutated. The addition of antagomir-208a reversed the Bcl-2-3'UTR suppression from stretching for 1 h. Flow cytometric analysis revealed that pre-treatment with miR-499 or antagomir-208a inhibited cellular apoptosis in stretched HCF-aa. In hearts with volume overload, miR-499 overexpression inhibited myocardial miR-208a expression, whereas Bcl-2 expression could be suppressed by the addition of miR-208a. In conclusion, miR-208a mediated the regulation of miR-499 on Bcl-2 expression in stretched HCF-aa and hearts with volume overload.

Prognostic impact of renal dysfunction on embolic stroke of undetermined source-Role beyond CHA2 DS2 -VASc score: Results from Taiwan Stroke Registry.

BACKGROUND AND PURPOSE: The CHA2 DS2 -VASc score has immense prognostic value in patients with embolic stroke of undetermined source (ESUS). We aimed to determine the usefulness of advanced renal dysfunction and its addition to the CHA2 DS2 -VASc score in improving predictive accuracy. METHODS: In total, 3775 ESUS patients were enrolled from a nationwide hospital-based prospective study. Advanced renal dysfunction was defined as estimated glomerular filtration rate <30 ml/min per 1.73 m2 or patients under dialysis. Clinical outcomes included recurrent stroke and 1-year all-cause mortality. Poor functional outcome was defined as a modified Rankin Scale >2 at first-, third-, and sixth-month post-stroke. The renal (R)-CHA2 DS2 -VASc score was derived by including advanced renal dysfunction in the CHA2 DS2 -VASc score. Risk stratification improvement after including advanced renal dysfunction was assessed using C statistic, integrated discrimination improvement (IDI), and category-free net reclassification index (NRI). RESULTS: After adjusting for confounding factors and CHA2 DS2 -VASc score, advanced renal dysfunction showed significant associations with all-cause mortality (HR: 2.88, 95% CI: 1.92-4.34) and poor functional outcome at third- (OR: 2.69, 95% CI: 1.47-4.94) and sixth-month post-stroke (OR: 2.67, 95% CI: 1.47-4.83). IDI and NRI showed that incorporating advanced renal dysfunction significantly improved risk discrimination over the original CHA2 DS2 -VASc score. R-CHA2 DS2 -VASc score ≥2 increased risk by 1.94-fold (95% CI: 1.15-3.27) for all-cause mortality, and ≥4 increased risk by 1.62-fold (95% CI: 1.05-2.50) of poor functional outcome at third-month post-stroke and by 1.81-fold (95% CI: 1.19-2.75) at sixth-month post-stroke. CONCLUSIONS: Advanced renal dysfunction was significantly associated with clinical and functional outcomes in ESUS patients and may improve prognostic impact of the CHA2 DS2 -VASc score.

Comparison of Arrhythmia Detection by 24-Hour Holter and 14-Day Continuous Electrocardiography Patch Monitoring.

BACKGROUND: Although 24-hour Holter monitoring is routinely used for patients with suspected paroxysmal arrhythmia, its sensitivity in detecting such arrhythmias is insufficient. METHODS: We compared a 14-day electrocardiography (ECG) monitor patch - a single-use, noninvasive, waterproof, continuous monitoring patch - with a 24-hour Holter monitor in 32 consecutive patients with suspected arrhythmia. RESULTS: The 14-day ECG patch was well tolerated, and its rates of detection of relevant arrhythmias on days 1, 3, 7, and 14 were 13%, 28%, 47%, and 66%, respectively. The detection rate of paroxysmal arrhythmias was significantly higher for the 14-day ECG patch than for the 24-hour Holter monitor (66% vs. 9%, p < 0.001). Among the 32 patients, 202 atrial fibrillation or atrial flutter episodes were detected in 6 patients (22%) with the 14-day ECG patch; however, only 1 atrial fibrillation episode was detected in a patient (3%, p < 0.05) with the 24-hour Holter monitor. Other clinically relevant arrhythmias recorded on the 14-day ECG patch included 21 (65.5%) episodes of supraventricular tachycardia, 2 (6.3%) long pause, and 2 (6.3%) ventricular arrhythmias. The mean dermal response score immediately after removal of the 14-day ECG patch from the patients was 0.64, which indicated minimal erythema. CONCLUSIONS: The 14-day ECG patch was well tolerated and allowed for longer continuous monitoring than the 24-hour Holter monitor, thus resulting in improved clinical accuracy in the detection of paroxysmal arrhythmias. Future studies should examine the long-term effectiveness of 14-day ECG patches for managing selected patients.

Antithrombotic Strategies in Patients with Atrial Fibrillation Following Percutaneous Coronary Intervention: A Systemic Review and Network Meta-Analysis of Randomized Controlled Trials.

Up to 10% of patients with atrial fibrillation (AF) undergo percutaneous coronary intervention (PCI). A systematic review and network meta-analysis were conducted by searching PubMed, Embase, and the Cochrane database of systematic reviews for randomized control trials that studied the safety and efficacy of different antithrombotic strategies in these patients. Six studies, including 12,158 patients were included. Compared to that in the triple antithrombotic therapy group (vitamin K antagonist (VKA) plus P2Y12 inhibitor and aspirin), thrombolysis in myocardial infarction (TIMI) major bleeding was significantly reduced in the dual antithrombotic therapy (non-vitamin K oral anticoagulants (NOACs) plus P2Y12 inhibitor) group by 47% (Odds ratio (OR), 0.53; 95% credible interval [CrI], 0.35-0.78; I2 = 0%). Besides, NOAC plus a P2Y12 inhibitor was associated with less intracranial hemorrhage compared to VKA plus single antiplatelet therapy (OR: 0.20, 95% CrI: 0.05-0.77). There was no significant difference in the trial-defined major adverse cardiac events or the individual outcomes of all-cause mortality, cardiovascular death, myocardial infarction, stroke or stent thrombosis among all antithrombotic strategies. In conclusion, antithrombotic strategy of NOACs plus P2Y12 inhibitor is safer than, and as effective as, the strategies including aspirin when used in AF patients undergoing PCI.

(-)-Epigallocatechin Gallate Promotes MicroRNA 145 Expression against Myocardial Hypoxic Injury through Dab2/Wnt3a/ß-catenin.

MicroRNA 145 (miR-145) is a critical modulator of cardiovascular diseases. The downregulation of myocardial miR-145 is followed by an increase in disabled-2 (Dab2) expression in cardiomyocytes. (-)-epigallocatechin gallate (EGCG) is a flavonoid that has been evaluated extensively due to its diverse pharmacological properties including anti-inflammatory effects. The aim of this study was to investigate the cardioprotective effects of EGCG under hypoxia-induced stress in vitro and in vivo. The hypoxic insult led to the suppression of miR-145 expression in cultured rat cardiomyocytes in a concentration-dependent manner. Western blotting and real-time PCR were performed. In rat myocardial infarction study, in situ hybridization, and immunofluorescent analyses were adopted. The western blot and real-time PCR data revealed that hypoxic stress with 2.5% O2 suppressed the expression of miR-145 and Wnt3a/ß-catenin in cultured rat cardiomyocytes but augmented Dab2. Treatment with EGCG attenuated Dab2 expression, but increased Wnt3a and ß-catenin in hypoxic cultured cardiomyocytes. Following in vivo myocardial infarction (MI) study, the data revealed the myocardial infarct area reduced by 48.5%, 44.6%, and 48.5% in EGCG (50mg/kg) or miR-145 dominant or Dab2 siRNA groups after myocardial infarction for 28 days, respectively. This study demonstrated that EGCG increased miR-145, Wnt3a, and ß-catenin expression but attenuated Dab2 expression. Moreover, EGCG ameliorated myocardial ischemia in vivo. The novel suppressive effect was mediated through the miR-145 and Dab2/Wnt3a/ß-catenin pathways.

Effect of atorvastatin on cardiomyocyte hypertrophy through suppressing MURC induced by volume overload and cyclic stretch.

MURC (muscle-restricted coiled-coil protein) is a hypertrophy-related gene. Hypertrophy can be induced by mechanical stress. The purpose of this research was to investigate the hypothesis that MURC mediates hypertrophy in cardiomyocytes under mechanical stress. We used the in vivo model of an aortocaval shunt (AV shunt) in adult Wistar rats to induce myocardial hypertrophy. We also used the in vitro model of cyclic stretch in rat neonatal cardiomyocytes to clarify MURC expression and the molecular regulation mechanism. The flexible membrane culture plate seeding with cardiomyocytes Cardiomyocytes seeded on a flexible membrane culture plate were stretched by vacuum pressure to 20% of maximum elongation at 60 cycles/min. AV shunt induction enhanced MURC protein expression in the left ventricular myocardium. Treatment with atorvastatin inhibited the hypertrophy induced by the AV shunt. Cyclic stretch markedly enhanced MURC protein and mRNA expression in cardiomyocytes. Addition of extracellular-signal-regulated kinase (ERK) inhibitor PD98059, ERK small interfering RNA (siRNA), angiotensin II (Ang II) antibody and atorvastatin before stretch, abolished the induction of MURC protein. An electrophoretic mobility shift assay showed that stretch enhanced the DNA binding activity of serum response factor. Stretch increased but MURC mutant plasmid, ERK siRNA, Ang II antibody and atorvastatin reversed the transcriptional activity of MURC induced by stretch. Adding Ang II to the cardiomyocytes also induced MURC protein expression. MURC siRNA and atorvastatin inhibited the hypertrophic marker and protein synthesis induced by stretch. Treatment with atorvastatin reversed MURC expression and hypertrophy under volume overload and cyclic stretch.

Real-World Experience with Idarucizumab to Reverse Anticoagulant Effect in Dabigatran-Treated Patients: Report of 11 Cases from Taiwan.

BACKGROUND: This study aims to observe the effectiveness and safety of idarucizumab in dabigatran-treated patients with severe bleeding or requiring surgery in Taiwan. METHODS AND RESULTS: In Taiwan, 11 dabigatran-treated patients developed severe bleeding, fracture that needed surgery, and acute ischemic stroke requiring thrombolysis. These patients were treated with idarucizumab and obtained adequate hemostasis. Our experiences reconfirmed the efficacy and safety of idarucizumab in Asian patients. CONCLUSIONS: Idarucizumab improves safety in dabigatran-treated patients. Continued education about the availability and appropriate use of idarucizumab is necessary in Asia.

Effects of flavonoids on MicroRNA 145 regulation through Klf4 and myocardin in neointimal formation in vitro and in vivo.

MicroRNA 145 (miR-145) is a critical modulator of vascular smooth muscle cell (VSMC) phenotyping and proliferation. Flavonoids have been studied extensively due to their diverse pharmacological properties, including anti-inflammatory effects. The aims of this study is designed to evaluate the atheroprotective effects on angiotensin II (Ang II)-induced miR-145 and Klf4/myocardin expression in vitro and in vivo of flavonoids, including (-)-epigallocatechin gallate (EGCG), chrysin, wogonin, silibinin, and ferulic acid. Ang II significantly reduced the miR-145 compared with the control VSMC groups; all the tested flavonoids increased miR-145 in the 100 nM concentration. Among the test compounds, EGCG showed the strongest augmenting effect on miR-145 and myocardin, however, it also abolished Ang II-induced Klf4. A [3H]-thymidine incorporation proliferation assay demonstrated that EGCG inhibited Ang II-induced VSMC proliferation, and Klf4 siRNA presented with the similar results. Immunohistochemical analysis and confocal microscopy demonstrated increased Klf4 expression and the arterial lumen was narrowed after balloon injury 14 days. With the addition of EGCG (50 mg/kg) and Klf4 siRNA, neointimal formation was reduced by 40.7% and 50.5% compared with balloon injury 14 days; Klf4 expression also was attenuated. This study demonstrated EGCG increased miR-145 and attenuated Klf4, and ameliorated neointimal formation in vitro and in vivo. The novel suppressive effect was mediated through the miR-145 and Klf4/myocardin pathways.

Coronary artery aneurysm after implantation of a bioresorbable vascular scaffold: Case report and literature review.

A 55-year-old man underwent successful percutaneous coronary intervention for the middle left circumflex artery with a 3.5 × 28-mm bioresorbable vascular scaffold (BVS). At 18 months, follow-up coronary angiography showed ectatic change with aneurysm formation over the BVS. Optical coherence tomography revealed absence of strut continuity at the aneurysm site, in the middle of the BVS. A literature review identified nine patients with intrascaffold aneurysm, including the present patient, which developed 6-32 months after BVS implantation. Of these nine patients, four underwent percutaneous coronary intervention for chronic total occlusion. The pathogenesis of coronary artery aneurysm is multifactorial. Most patients receive no further intervention, but long-term dual antiplatelet therapy is sometimes prescribed in conjunction with regular follow-up. © 2017 Wiley Periodicals, Inc.

Atorvastatin alleviates cardiomyocyte apoptosis by suppressing TRB3 induced by acute myocardial infarction and hypoxia.

BACKGROUND/PURPOSE: TRB3 (tribbles 3), an apoptosis-regulated gene, increases during endoplasmic reticulum stress. Hypoxia can induce inflammatory mediators and apoptosis in cardiomyocytes. However, the expression of TRB3 in cardiomyocyte apoptosis under hypoxia is not thoroughly known. We investigated the regulation mechanism of TRB3 expression and apoptosis induced by hypoxia in cardiomyocytes. METHODS: An in vivo model of acute myocardial infarction (AMI) was applied in adult Wistar rats to induce myocardial hypoxia. Rat neonatal cardiomyocytes were subjected to 2.5% O2 to induce hypoxia. RESULTS: The expression of TRB3 was evaluated in cultured rat neonatal cardiomyocytes subjected to hypoxia. Hypoxia significantly enhanced TRB3 protein and mRNA expression. Adding c-jun N-terminal kinase (JNK) inhibitor SP600125, JNK small interfering RNA (siRNA), tumor necrosis factor-α (TNF-α) antibody, and atorvastatin 30 minutes before hypoxia reversed the induction of TRB3 protein. A gel-shift assay showed the DNA-binding activity of growth arrest and DNA damage-inducible gene 153 (GADD153), which increased after hypoxia. Hypoxia increased, whereas the TRB3-mut plasmid, SP600125, and TNF-α antibody abolished the hypoxia-induced TRB3 promoter activity. Hypoxia increased the secretion of TNF-α from cardiomyocytes. Exogenous administration of TNF-α recombinant protein to the cardiomyocytes without hypoxia increased TRB3 protein expression, similar to that observed after hypoxia. Hypoxia-induced cardiomyocyte apoptosis is inhibited by TRB3 siRNA, the TNF-α antibody, and atorvastatin. Atorvastatin reduced the TRB3 expression and cardiomyocyte apoptosis induced by AMI. Hypoxia induces TRB3 through TNF-α, JNK, and the GADD153 pathway. CONCLUSION: Treatment of atorvastatin inhibits the expression of TRB3 and cardiomyocyte apoptosis induced by AMI and hypoxia.