Conversion of the bronchial tree into a conforming electrode to ablate the lung nodule in a porcine model.

BACKGROUND: Radiofrequency ablation (RFA) is one of the treatment options for lung nodules. However, the need for exact delivery of the rigid metal electrode into the center of the target mass often leads to complications or suboptimal results. To overcome these limitations, a concept of conforming electrodes using a flexible material has been tested in this study. METHODS: A bronchoscopy-guided RFA (CAROL) under a temperature-controlled mode was tested in in-vivo and ex-vivo porcine lungs. Gallium-based liquid metal was used for turning the bronchial tree into temporary RF electrodes. A customized bronchoscopy-guided balloon-tipped guiding catheter (CAROL catheter) was used to make the procedure feasible under fluoroscopy imaging guidance. The computer simulation was also performed to gain further insight into the ablation results. Safety was also assessed including the liquid metal remaining in the body. RESULTS: The bronchial electrode injected from the CAROL catheter was able to turn the target site bronchial air pipe into a temporally multi-tined RF electrode. The mean volume of Gallium for each effective CAROL was 0.46 ± 0.47 ml. The ablation results showed highly efficacious and consistent results, especially in the peripheral lung. Most bronchial electrodes were also retrieved by either bronchoscopic suction immediately after the procedure or by natural expectoration thereafter. The liquid metal used in these experiments did not have any significant safety issues. Computer simulation also supports these results. CONCLUSION: The CAROL ablation was very effective and safe in porcine lungs showing encouraging potential to overcome the conventional approaches.

Lung cancer can be treated by inserting a metal device into the lung via the throat and using this to send radio waves into the cancer. However, using a rigid metal device can cause damage to other areas of the lung and can only treat small cancers. Here, we describe an alternative method to treat lung cancers in which liquid metal is used to fill the spaces within the lung closest to the cancer. We demonstrate that this method can be used to treat cancer in a swine model of lung cancer. Given the positive results we obtained, we think this approach should be tested in a clinical trial in human patients with lung cancer, as it might improve cancer treatment.

The Development of a Permanent Implantable Spacer with the Function of Size Adjustability for Customized Treatment of Regurgitant Heart Valve Disease.

The Pivot Mandu is an innovative device featuring a leak-tight adjustable 3D balloon spacer, incorporating inner mesh support, an outer e-PTFE layer, and a compliant balloon in the middle layer with a specialized detachable system. To assess its feasibility, proof of concept was rigorously evaluated through bench testing and survival porcine animal experiments. The results demonstrated successful remote inflation of the balloon system, with the balloon spacer exhibiting sustained patent and functional integrity over an extended observation period of up to 6 months. A noteworthy feature of the newly designed 3D balloon spacer is its capability for easy size adjustment during procedures, enhancing its adaptability and practicality in clinical settings. This three-layered 3D balloon spacer, with its established long-term patency, exhibits highly encouraging outcomes that hold promise in overcoming the current limitations of spacer devices for heart valve diseases. Given the compelling results from preclinical investigations, the translation of the Pivot Mandu into human trials is strongly warranted.

Direct Extracorporeal Membrane Oxygenation Bridged Heart Transplantation: The Importance of Multi-Organ Failure.

Background and Objectives: Recently, approximately 40% of all heart transplantation (HTx) in South Korea are performed using the direct extracorporeal membrane oxygenation (ECMO) bridging method. We conducted a study to examine the clinical outcome of direct ECMO-bridged HTx and to investigate the impact of multi-organ failure (MOF). Methods: From June 2014 to September 2022, a total of 96 adult patients who underwent isolated HTx at a single tertiary hospital were included in the study. The patients were sub-grouped into ECMO (n=48) and non-ECMO group (n=48), and the ECMO group was subdivided into awake (n=22) and non-awake (n=26) groups based on mechanical ventilator (MV) dependency. Baseline characteristics, 30-day, and 1-year mortality were analyzed retrospectively. Results: The 1-year survival rate was significantly lower in the ECMO group (72.9% vs. 95.8%, p=0.002). There was a significant difference in the 30-day survival rate between the awake and non-awake ECMO groups (81.8% vs. 65.4%, p=0.032). In the univariate analysis of logistic regression for 1-year mortality, the odds ratio was 8.5 for ECMO bridged HTx compared to the non-ECMO group, 12.3 in patients who required MV (p=0.003), and 23 with additional hemodialysis (p<0.001). Conclusions: Patients who required MV in ECMO bridged HTx showed higher preoperative MOF rates and early mortality than those extubated. When considering ECMO bridged HTx, the severity of MOF should be thoroughly investigated, and careful patient selection is necessary.

Comparison of 2 Different Paclitaxel-Coated Balloons in Coronary In-Stent Restenosis: A Randomized Controlled Trial.

Background: Drug-coated balloons (DCBs) offer an effective treatment for in-stent restenosis (ISR). The Genoss DCB is a novel paclitaxel-coated balloon with a shellac plus vitamin E excipient that enhances drug delivery to the target lesion, minimizing restenosis. Objectives: This study aimed to investigate the angiographic efficacy, clinical safety, and effectiveness of the novel shellac plus vitamin E-based DCB in a randomized controlled trial designed to enable regulatory approval of this new device in South Korea. Methods: This noninferiority trial randomized patients experiencing their first ISR to the novel shellac plus vitamin E-based DCB or the reference SeQuent Please iopromide-based DCB in a 1:1 ratio. All patients underwent planned angiographic and clinical follow-up at 6 months. The study was powered for the primary endpoint of 6 months in-segment late lumen loss (LLL). Results: A total of 82 patients from 7 centers were randomized to either the novel shellac plus vitamin E-based DCB group (n = 41) or the reference iopromide-based DCB group (n = 41). The 6-month in-segment LLL was 0.15 ± 0.43 mm with the novel DCB compared with 0.24 ± 0.39 mm with the reference device. The 1-sided 97.5% upper confidence limit of the difference was 0.13 mm, lower than the noninferiority limit of 0.29 mm, achieving noninferiority (P for noninferiority = 0.001). Major cardiovascular events were comparable between 2 groups at 6 months (7.7% for the novel DCB vs 10.3% for the reference DCB; P = 0.692). Conclusions: In this multicenter, head-to-head comparison randomized trial, the novel shellac plus vitamin E-based DCB showed a comparable result to the reference iopromide-based device for the primary endpoint of 6-month in-segment LLL for the treatment of coronary ISR. (Compare the Safety and Efficacy of Genoss® DCB and SeQuent® Please in Korean Patient With Coronary In-stent Restenosis; NCT04405063).

The Cobra Catheter: A Novel Concept and Device for the Thru-Septal Myocardium Approach.

Objectives: In our previous study, we suggested the novel septal traversing technique as effective and safe in catheter-based approach for septal myocardium. However, it is limited by its dependence on the septal perforator vein. This study aimed to evaluate the Cobra catheter as a backup catheter to overcome this limitation in swine. Methods: We designed the guiding Cobra catheter. It consisted of three major parts (the external pull-wire steerable distal tip, the C-shaped shaft, and the steering adjustment handle). We tested the difference in force between the guidewire passing through the muscle and the vessel wall using a push-pull gauge. We performed a septal wire engage procedure in swine using the Cobra catheter. The guidewire engagement of the septal vein and Cobra catheter were compared visually and histopathologically. Results: A total of ten swine were enrolled in this study. The success rate was 100% under fluoroscopy. The experiments confirmed the medical potential of the septal approach even in a location irrelevant to the septal perforator vein anatomy and confirmed that the wire passed well in the target direction in the harvested heart. There was no serious physical damage or pathological abnormalities in the vessel wall and myocardium. Conclusion: These results showed that the novel Cobra catheter with a septal vein-independent trans-septal approach may be a safe and effective alternative for the treatment of structural heart diseases.

A Novel Device for Tricuspid Regurgitation Reduction Featuring 3-Dimensional Leaflet and Atraumatic Anchor: Pivot-TR System.

A new device called the Pivot-TR system was designed to treat tricuspid regurgitation with a novel spacer crossing the valve vertically. Its unique atraumatic anchoring system composed of both the elephant long nose and the inferior vena cava spiral anchor, in addition to the relatively easy implantation mechanism, enabled easy retrieval of the system later on. The system showed promising feasibility and safety results in this swine-based animal experiment, which should encourage human translation study.

Pharmacodynamic Profile and Prevalence of Bleeding Episode in East Asian Patients with Acute Coronary Syndromes Treated with Prasugrel Standard-Dose versus De-escalation Strategy: A Randomized A-MATCH Trial.

Compared with Caucasian patients, East Asian patients have the unique risk-benefit trade-off and different responsiveness to antithrombotic regimens. The aim of this study was to compare pharmacodynamic profile in East Asian patients with acute coronary syndromes (ACSs) treated with prasugrel standard-dose versus a de-escalation strategy. Before discharge, ACS patients with age <75 years or weight ≥60 kg (n = 255) were randomly assigned to the standard-dose (10-mg group) or de-escalation strategy (5-mg group or platelet function test [PFT]-guided group). After 1 month, VerifyNow P2Y12 assay-based platelet reactivity (P2Y12 reaction unit [PRU]) and bleeding episodes were evaluated. Primary endpoint was the percentage of patients with the therapeutic window (85 ≤ PRU ≤ 208). The 250 patients completed 1-month treatment. The percentage of patients within the therapeutic window was significantly lower in the 10-mg group (n = 85) compared with the 5-mg (n = 83) and PFT-guided groups (n = 82) (35.3 vs. 67.5 vs. 65.9%) (odds ratio [OR]: 3.80 and 3.54; 95% confidence interval [CI]: 2.01-7.21 and 1.87-6.69, respectively). Compared with the 10-mg group, the bleeding rate was tended to be lower with de-escalation strategies (35.3 vs. 24.1% vs. 23.2%) (hazard ratio [HR]: 0.58 and 0.55; 95% CI: 0.30-1.14 and 0.28-1.09, respectively). "PRU < 127" was the optimal cut-off for predicting 1-month bleeding events (area under the curve: 0.616; 95% CI: 0.543-0.689; p = 0.005), which criteria was significantly associated with early discontinuation of prasugrel treatment (HR: 2.00; 95% CI: 1.28-3.03; p = 0.001). In conclusion, compared with the standard-dose prasugrel, the prasugrel de-escalation strategy in East Asian patients presented with ACS showed a higher chance within the therapeutic window and a lower tendency toward bleeding episodes. REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier:NCT01951001.

Optimal strategy for side branch treatment in patients with left main coronary bifurcation lesions.

INTRODUCTION AND OBJECTIVES: There are no guidelines regarding the most appropriate approach for provisional side branch (SB) intervention in left main (LM) bifurcation lesions. METHODS: The present prospective, randomized, open-label, multicenter trial compared conservative vs aggressive strategies for provisional SB intervention during LM bifurcation treatment. Although the trial was designed to enroll 700 patients, it was prematurely terminated due to slow enrollment. For 160 non-true bifurcation lesions, a 1-stent technique without kissing balloon inflation was applied in the conservative strategy, whereas a 1-stent technique with mandatory kissing balloon inflation was applied in the aggressive strategy. For 46 true bifurcation lesions, a stepwise approach was applied in the conservative strategy (after main vessel stenting, SB ballooning when residual stenosis> 75%; then, SB stenting if residual stenosis> 50% or there was a dissection). An elective 2-stent technique was applied in the aggressive strategy. The primary outcome was a 1-year target lesion failure (TLF) composite of cardiac death, myocardial infarction, or target lesion revascularization. RESULTS: Among non-true bifurcation lesions, the conservative strategy group used a smaller amount of contrast dye than the aggressive strategy group. There were no significant differences in 1-year TLF between the 2 strategies among non-true bifurcation lesions (6.5% vs 4.9%; HR, 1.31; 95%CI, 0.35-4.88; P=.687) and true bifurcation lesions (17.6% vs 21.7%; HR, 0.76; 95%CI, 0.20-2.83; P=.683). CONCLUSIONS: In patients with a LM bifurcation lesion, conservative and aggressive strategies for a provisional SB approach have similar 1-year TLF rates.

Septal Reduction Using Transvenous Intramyocardial Cerclage Radiofrequency Ablation: Preclinical Feasibility.

Debulking of left ventricular septal mass is typically accomplished using surgical myectomy, which is morbid, or using transcoronary alcohol septal ablation, which can result in geographic miss and occasional catastrophic nontarget coronary injury. The authors developed and tested operational parameters in vitro and vivo for a device to accomplish transvenous intraseptal radiofrequency ablation to reduce ventricular septal mass using a technique derived from mitral cerclage, which the authors call cerclage ablation. Cerclage ablation appeared feasible in vitro and safe and effective in vivo. Cerclage ablation is an attractive new approach to debulk the interventricular septum in obstructive hypertrophic cardiomyopathy. These data support clinical investigation.

Incidence of Cardiovascular Events and Safety Profile of Prasugrel in Korean Patients With Acute Coronary Syndrome.

BACKGROUND: Dual antiplatelet therapy is commonly used for patients with acute coronary syndrome (ACS). This study aimed to evaluate the safety and efficacy of aspirin and prasugrel at standard dosages in Korean patients using clinical outcome data.Methods and Results:For this prospective multicenter phase IV post-marketing surveillance (PMS) study, ACS patients from 29 July 2012 to 28 July 2016 were recruited. Patients received aspirin at a dose of 75-150 mg daily and a standard dose of prasugrel. Bleeding events were recorded and summarized to evaluate safety. Data on adverse events (AEs) and composite events such as cardiovascular (CV) death, myocardial infarction (MI), and stroke were recorded and summarized to assess efficacy. Of the 3,283 patients recruited, data from 3,110 and 3,044 patients were included in the safety and efficacy analyses, respectively (median treatment duration, 172 days). The most frequently reported AE was ecchymosis (2.8%). The number of patients with major bleeding was 29/3,110 (0.93%). The discontinuation rate for any reason was 12.6%. The number of cases that ended in CV death, MI, stroke, stent thrombosis, or unplanned coronary revascularization was 26/3,044 (0.85%). CONCLUSIONS: The present results are similar to those observed in clinical trials where administration of low-dose aspirin plus prasugrel was associated with a low rate of major bleeding and CV events.

Effect of membrane insertion for tricuspid regurgitation using immersed-boundary lattice Boltzmann method.

BACKGROUND: Tricuspid regurgitation is treated by valve repair or replacement. However, these methods have limitations, and alternative treatment methods are therefore required. OBJECTIVES: In this study, a new method of tricuspid valve treatment using artificial membrane insertion is analyzed. We performed tricuspid valve simulations using an artificial membrane inserted into the right ventricle (RV) or right atrium (RA). METHODS: We use the lattice Boltzmann method with the immersed boundary condition to model the structural motion of the valve leaflet. The effect of membrane insertion is analyzed in terms of the stress, force, and impulse on the valve leaflet, along with the velocity, pressure, jet volume, and Reynolds stress in the flow field. RESULTS: While the use of either membrane (RA or RV) leads to improved valve closure relative to the use of no membrane, the RV membrane is more effective than the RA membrane in achieving improved valve closure. In addition, a larger membrane area with a shorter distance between the leaflet and membrane increases membrane efficacy. CONCLUSION: Our results suggest that membrane insertion can form an effective new method for the treatment of tricuspid regurgitation.

Computational analysis of the electromechanical performance of mitral valve cerclage annuloplasty using a patient-specific ventricular model.

We aimed to propose a novel computational approach to predict the electromechanical performance of pre- and post-mitral valve cerclage annuloplasty (MVCA). Furthermore, we tested a virtual estimation method to optimize the left ventricular basement tightening scheme using a pre-MVCA computer model. The present model combines the three-dimensional (3D) electromechanics of the ventricles with the vascular hemodynamics implemented in a lumped parameter model. 3D models of pre- and post-MVCA were reconstructed from the computed tomography (CT) images of two patients and simulated by solving the electromechanical-governing equations with the finite element method. Computed results indicate that reduction of the dilated heart chambers volume (reverse remodeling) appears to be dependent on ventricular stress distribution. Reduced ventricular stresses in the basement after MVCA treatment were observed in the patients who showed reverse remodeling of heart during follow up over 6 months. In the case who failed to show reverse remodeling after MVCA, more virtual tightening of the ventricular basement diameter than the actual model can induce stress unloading, aiding in heart recovery. The simulation result that virtual tightening of the ventricular basement resulted in a marked increase of myocardial stress unloading provides in silico evidence for a functional impact of MVCA treatment on cardiac mechanics and post-operative heart recovery. This technique contributes to establishing a pre-operative virtual rehearsal procedure before MVCA treatment by using patient-specific cardiac electromechanical modeling of pre-MVCA.

Effects of 12-Week Resistance Exercise on Electroencephalogram Patterns and Cognitive Function in the Elderly With Mild Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To investigate the effects of a 12-week resistance exercise program with an elastic band on electroencephalogram (EEG) patterns and cognitive function in elderly patients with mild cognitive impairment (MCI). DESIGN: Randomized controlled trial. SETTING: Community center. PARTICIPANTS: Twenty-two subjects with MCI and 25 healthy volunteer subjects were randomly assigned to 1 of 4 groups: subjects with MCI who undertook the exercise program (MCI-EX; n = 10), an MCI control group (MCI-Con; n = 12), a healthy volunteer exercise group (NG-EX; n = 12), and a healthy volunteer control group (NG-Con; n = 13). INTERVENTION: The exercise group engaged in a 15-repetition maximum (15RM; 65% of 1RM) resistance exercise program for 12 weeks. MAIN OUTCOME MEASURES: Electroencephalograms, neuropsychological tests, and Senior Fitness Test. RESULTS: The 12-week 15RM (65% of 1RM) resistance exercise program significantly improved variables related to the physical fitness of the elderly subjects. Furthermore, for the EEG test, the MCI and NG groups showed significant differences at baseline in relative beta waves on electrodes Fp1 (P < 0.05) and F3 (P < 0.05), as well as in relative beta2 waves on F3 (P < 0.05). In addition, after the 12-week exercise intervention, differences in a region that benefits from exercise were observed between (1) the MCI-EX group in the relative theta power on F3 (P < 0.05) and the relative alpha power on T3 (P < 0.05) and in (2) the NG-EX group in the relative theta power on P3 (P < 0.05) and P4 (P < 0.01). In addition, only the score of the digit span backward in the MCI-EX group changed significantly (P < 0.05). CONCLUSIONS: The 12-week resistance exercise with an elastic band had a positive effect on EEG patterns in elderly subjects with MCI, along with providing physical benefits and slight changes in cognitive function in MCI-EX group. SIGNIFICANCE: A 15RM resistance exercise program can be an effective treatment for delaying cognitive decline and improving physical fitness.

Mitochondrial ATP-Sensitive Potassium Channels Play a Role in Reducing Both Myocardial Infarction and Reperfusion Arrhythmia in Remote Ischemic Preconditioned Hearts.

BACKGROUND: Mitochondrial ATP-sensitive potassium (mKATP) channels play a role in reperfusion arrhythmias (RAs) in ischemia-reperfusion (I/R) injury. Evidence suggests that remote ischemic preconditioning (RIPC) reduces RAs, however not much is known on the mechanistic role of mKATP in RIPC. We evaluated whether mKATP channels are associated with reducing arrhythmia and infarct size in RIPC. METHODS: Isolated rat hearts received 30 minutes of regional ischemia followed by 2 hours of reperfusion through the Langendorff perfusion system. RIPC was induced by 3 cycles of 5 minutes occlusion and 5 minutes release of the bilateral femoral artery. The animals were randomly divided into 4 groups as follows: 1) CON, I/R injury but not RIPC, 2) RIPC, 3) HD+RIPC, pretreatment of the selective mKATP channel blocker, 5-hydroxydecanoate (5-HD), in RIPC, and 4) HD, pretreatment of 5-HD in CON. Cardiodynamics and infarct size were determined. The severity of arrhythmia was quantitated via the Curtis and Walker scoring system as well as the Lepran scoring system. RESULTS: RIPC significantly reduced the infarct size over AR (25.7 ± 2.6%) compared to CON (37.0 ± 2.6%, P < 0.05). The selective mKATP channel blocker 5-HD significantly inhibited the infarct-reducing effect of RIPC (39.3 ± 3.0%, P < 0.05 vs. RIPC). Additionally, RIPC significantly reduced the arrhythmia score compared to CON (14.6 ± 1.9 to 8.7 ± 0.4, P = 0.023, by Curtis and Walker's system, 16.1 ± 2.1 to 9.1 ± 0.5, P = 0.006, by Lepran's system). The anti-arrhythmic effect of RIPC was blocked by 5-HD (15.5 ± 1.6 and 16.0 ± 1.2, by Curtis and Walker's and Lepran's system, respectively). CONCLUSIONS: The selective mKATP channel blocker, 5-HD, inhibited the infarct-limitation and anti-arrhythmic effect of RIPC. The mKATP channels play a role in the reduction of both infarct size and RAs in RIPC.

Mitral Loop Cerclage Annuloplasty for Secondary Mitral Regurgitation: First Human Results.

OBJECTIVES: This is an early feasibility clinical test of mitral loop cerclage annuloplasty to treat secondary mitral valve regurgitation. BACKGROUND: Secondary mitral regurgitation is characterized by cardiomyopathy, mitral annular enlargement, and leaflet traction contributing to malcoaptation. Transcatheter mitral loop cerclage applies circumferential compression to the mitral annulus by creating a loop through the coronary sinus across the interventricular septum, protecting entrapped coronary arteries from compression, and interactive annular reduction under echocardiographic guidance. This is the first human test of mitral loop annuloplasty. METHODS: Five subjects with severe symptomatic secondary mitral regurgitation underwent mitral loop cerclage, with echocardiographic and computed tomography follow-up over 6 months. RESULTS: Mitral loop cerclage was successful in 4 of 5 subjects and aborted in 1 of the 5 because of unsuitable septal coronary vein anatomy. Immediately and over 6 months, measures of both mitral valve regurgitation (effective orifice area and regurgitation fraction) and chamber dimensions (left atrial and left ventricular volumes) were reduced progressively and ejection fractions increased. Two with persistent and permanent atrial fibrillation spontaneously reverted to sinus rhythm during follow-up. One subject experienced a small myocardial infarction from an unrecognized small branch coronary occlusion. Another, experiencing cardiogenic shock at baseline, died of intractable heart failure after 6 weeks. CONCLUSIONS: In this first human test, mitral loop cerclage annuloplasty was successful in 4 of 5 attempts, caused reverse remodeling (reduction in secondary mitral regurgitation and heart chamber volumes), and suggested electrical remodeling (reversion of atrial fibrillation). Further evaluation is warranted.

Mitral loop cerclage as a variant form of mitral cerclage annuloplasty that adds a device (CSTV) for preventing potential complications: a preclinical proof of concept and feasibility study.

AIMS: Although mitral cerclage annuloplasty can reduce mitral regurgitation, the potential risks for erosion of the surrounding tissue or conduction blockage are barriers to human translation. This preclinical study aimed to provide a proof of concept for a novel approach, mitral loop cerclage (MLC), designed to address these shortcomings. METHODS AND RESULTS: MLC consists of: (1) a novel appliance termed a coronary sinus and tricuspid valve protective device (CSTV) that includes a tension locker, and (2) a nylon-coated, braided stainless steel rope (0.6 mm thick) with a coronary artery protective device in a single unit (cerclage rope). Nine healthy farm swine underwent MLC in short-term (two weeks, n=4) and midterm (six weeks, n=5) survival experiments under X-ray fluoroscopic guidance imaging. The procedural success rate was 100%. MLC resulted in a significant reduction of the septal lateral dimension of the mitral annulus (24.58±2.16 vs. 21.26±1.43 mm, p=0.04) and left ventricular (LV) volume in diastole (75.9±3.9 vs. 70.6±5.0 ml, p=0.04) in the midterm group. No conduction abnormalities or serious complications were noted beyond trivial tricuspid regurgitation in all cases (n=9). Necropsy showed no evidence of tissue erosion and an excellent biocompatibility of the implanted devices. CONCLUSIONS: MLC, as a novel approach for catheter-based mitral valve repair, appeared feasible in this short-term preclinical model. Further studies with longer follow-up in a cardiomyopathic animal model are needed to verify the clinical feasibility and safety of MLC.

Antiplatelet effect of ticagrelor compared to tirofiban in non-ST-segment elevation ACS patients undergoing PCI. The result of the TE-CLOT trial.

Addition of a potent P2Y12 inhibitor to aspirin is the standard therapy for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients undergoing percutaneous coronary intervention (PCI). Glycoprotein IIb/IIIa inhibitor, together with antiplatelet therapy, may be considered as part of initial therapy in NSTE-ACS patients with high-risk features. This study investigated the antiplatelet effect of ticagrelor loading dose (LD) versus tirofiban bolus injection with a post-bolus infusion on top of aspirin among NSTE-ACS patients planned to PCI. NSTE-ACS patients were randomised to receive either ticagrelor (n = 47) or tirofiban (n = 48). Platelet reactivity was assessed by light transmittance aggregometry at 0, 2, 8, and 24 hours (h) after treatment initiation. Primary endpoint was inhibition of platelet aggregation (IPA, 20 µM ADP, final extent) at 2 h after LD therapy, with a non-inferiority margin of 10%. The prevalence of high on-treatment platelet reactivity (HPR) was also compared at 0, 2, 8, and 24 h. The mean difference in IPA between ticagrelor and tirofiban was -9.9% (95% confidence interval: -25.7% to 5.9%) at 2 h, -1.6% (-8.0% to 4.8%) at 8 h, and -3.3% (-18.4% to 12.0%) at 24 h. The prevalence of HPR did not differ between the two groups at any time point (all p values ≥ 0.059), which was almost abolished by 8 h post-LD (< 5%). In conclusion, the antiplatelet effect during the early phase (~2 h) after ticagrelor LD appeared to be relatively strong, but it did not reach that of tirofiban in NSTE-ACS patients.

Remifentanil postconditioning has cross talk with adenosine receptors in the ischemic-reperfused rat heart.

BACKGROUND: Although there is a possibility of cross talk between opioid and adenosine signaling pathways in the ischemic-reperfused myocardium, it is not clear that an ultra-short-acting opioid receptor agonist remifentanil-induced postconditioning (RPostC) has cross talk with adenosine receptor (ADR). The purpose of this study was to determine whether there is cross talk with ADR in RPostC. MATERIALS AND METHODS: Isolated rat hearts were subjected to 30 min of regional ischemia and 2 h of reperfusion. RPostC was induced by 100 ng/mL of remifentanil perfusion, 5 min before reperfusion, followed by 5 min of reperfusion. The nonspecific opioid receptor antagonist naloxone (NAL) and the nonspecific ADR antagonist 8-(p-sulfophenyl) theophylline hydrate (8-SPT) were perfused for a 20-min period, 10 min before RPostC to the end of RPostC. Western blot analysis was performed to detect phospho-ERK1/2 in cultured cardiomyocytes. RESULTS: In cultured cardiomyocytes, remifentanil incubation significantly increased the phosphorylation of ERK1/2 and this effect was blocked by both NAL and 8-SPT (P < 0.01 and P < 0.05, respectively). RPostC significantly reduced infarct size over ischemic area at risk from 34.1 ± 10.5% to 16.6 ± 7.5% (P < 0.05 versus control). The infarct-limitation effect of RPostC was reversed by both NAL (33.8 ± 13.0%, P < 0.05) and 8-SPT (35.7 ± 14.5%, P < 0.01). CONCLUSIONS: This study strongly implies that the intracellular signaling pathways of cardioprotection by RPostC has cross talk with ADR in the ischemic-reperfused myocardium.

A randomised, multicentre, double blind, placebo controlled trial to evaluate the efficacy and safety of cilostazol in patients with vasospastic angina.

OBJECTIVES: We conducted a randomised, double blind, placebo controlled trial to assess the efficacy and safety of cilostazol, a selective inhibitor of phosphodiesterase 3, in patients with vasospastic angina (VSA). BACKGROUND: Cilostazol has been shown to induce vascular dilatation, but its efficacy in patients with VSA is unknown. METHODS: Between October 2011 and July 2012, 50 patients with confirmed VSA who had ≥1 angina episodes/week despite amlodipine therapy (5 mg/day) were randomly assigned to receive either cilostazol (up to 200 mg/day) or placebo for 4 weeks. All patients were given diaries to record the frequency and severity of chest pain (0-10 grading). The primary endpoint was the relative reduction of the weekly incidence of chest pain. RESULTS: Baseline characteristics were similar between the two groups. Among 49 evaluable patients (25 in the cilostazol group, 24 in the placebo group), the primary endpoint was significantly greater in the cilostazol group compared with the placebo group (-66.5±88.6% vs -17.6±140.1%, respectively, p=0.009). The secondary endpoints, including a change in the frequency of chest pain (-3.7±0.5 vs -1.9±0.6, respectively, p=0.029), a change in the chest pain severity scale (-2.8±0.4 vs -1.1±0.4, respectively, p=0.003), and the proportion of chest pain-free patients (76.0% vs 33.3%, respectively, p=0.003) also significantly favoured cilostazol. Headache was the most common adverse event in both groups (40.0% vs 20.8%, respectively, p=0.217). CONCLUSIONS: Cilostazol is an effective therapy for patients with VSA uncontrolled by conventional amlodipine therapy, and has no serious side effects. TRIAL REGISTRATION NUMBER: NCT01444885.