Intracoronary Administration Research Articles

Safety and Efficacy of Intracoronary Ad-HGF Administration for Treating Severe Coronary Disease: Results From Long-Term Follow-Up of a Phase I Clinical Trial

Objective: This study is a long-term follow-up of our previous phase I clinical trial and aims at evaluating the long-term safety and efficacy of intracoronary Ad-HGF administration for treating coronary disease. Methods: This study includes 22 patients (11 in the experiment group and 11 in the control group) with diffused and severe coronary disease who had received the optimal standardized medication therapy and was not amenable to revascularization. Intracoronary Ad-HGF gene transfer was administered to the distal part of the accessible artery by over-the wire balloon or at the ostium of the target vessels by diagnostic coronary catheter in the experiment group. Safety parameters were measured and compared between baseline and follow-ups (5-week; 12-month; 36- month) only in the experiment group. The changes of efficacy parameters (ejection fraction, EF) from baseline to 36- month follow-up (δEF) were measured in both groups and compared with each other. Results: This study confirmed the long-term safety of intracoronary Ad-HGF administration for treating severe diffuse coronary disease. All the eleven patients of the experiment group were alive after 36-months follow-up. During the follow-up, no new-onset arrhythmia was recorded; no malignant tumor was diagnosed; no paroxysmal or long-term fever was recorded; no retinal vascular anomaly was diagnosed. There were no statistically significant differences between the follow-ups and baseline in regard to blood parameters, including WBC, Hb, ALT, AST, BUN, Cr, CEA and AFP. In addition, intracoronary Ad-HGF efficiently improved echocardiographic EF at the 36-month follow-up compared to baseline (F=4.4, p=0.024) and with the control group (δEF: 3.5 ± 1.1 vs. -4.5 ± 1.3, MD: 8, p=0.0001). The medium-high dose subgroup also showed higher ECT-EF at the 36-month follow-up than baseline (MD: 4.8, p=0.017, n=8) and higher improvement of ECT-EF than the control group (δEF: 4.8 ± 1.5 vs. 0.3 ± 1.7, MD: 4.5, p=0.08). Conclusion: Intracoronary Ad-HGF administration is safe and potentially efficient in improving EF of patients with severe diffuse coronary disease in 3-year follow-up.

Intracoronary administration of levosimendan in patients with acute coronary syndromes and decreased left ventricular ejection fraction undergoing coronary artery bypass graft surgery

In cardiac surgery patients, intracoronary (IC) administration of levosimendan can provide optimal drug spread, enabling ef-fective manifestation of favorable drug effects and avoiding potentially harm-ful systemic hypotension. This could be beneficial in acute coronary syndromes (ACS) with decreased left ventricular ejec-tion fraction (LVEF). We present ten cases of IC administration of levosimendan in ACS manifested as ST segment elevation myocardial infarction, non-ST segment el-evation myocardial infarction or unstable angina pectoris. All patients underwent coronary artery bypass graft (CABG) sur-gery, performed as an “off-pump” or “on-pump”/“off-clamp” procedure (latter one with the use of cardiopulmonary bypass on the beating heart). Levosimendan was ad-ministered as an IC bolus (125-250 μg) in each coronary artery graft (2-3 grafts). In-travenous (IV) levosimendan infusion con-tinued (0.1-0.2 μg•kg-1•min-1) after graft placements (24-48 h), with IV infusion of norepinephrine (0.1 mg•ml-1), if needed. Cardiac function was assessed using LVEF (%) (Teicholz), thermodilution cardiac in-dex (CI) (ml•m-2), and systemic vascular resistance (SVR) (dynes•sec•cm-5). Nonparametric Wilcoxon signed-ranks test [presented as median (MED) with interquartile range (IQR)] indicated a sig-nificant difference between preoperative vs. immediate postoperative CI, SVR, and LVEF in all cases [2.2 (1.9-2.5) vs. 3.1 (2.9-3.4) ml•m-2, 1173.0 (1062.7-1278.2) vs. 882.5 (763.5-993.0) dynes•sec•cm-5, 44.5 (36.0-46.7) vs. 53.5 (45.7-59.2) %, respec-tively] (P=0.005), i.e. IC administration of levosimendan was associated with prompt improvement of intraoperative hemody-namics and cardiac contractility. IC ad-ministration of levosimendan may be a promising alternative method for improv-ing decreased cardiac function in acute cardiac ischemia, besides necessary surgi-cal revascularization.

Aspiracija tromba tokom primarne perkutane koronarne intervencije - gde smo sada?

Introduction. thrombus aspiration is not recommended as a routine procedure considering the results of large randomised trials. It is necessary to define new indications for thrombus aspiration in myocardial infarction and to conduct appropriate trials. The aim of this paper was to report a patient with successful aspiration of large thrombus mass from right coronary artery made after primary balloon angioplasty, and to consider which patients could benefit with this procedure. Case report. a male, 80 years old, has been admitted to a catheterisation laboratory with clinical, biochemical and electrocardiographic signs of acute myocardial infarction with ST segment elevation (STEMI) of inferoposterolateral localisation along with sinus bradycardia and profound arterial hypotension, which all are characteristic for inferior myocardial wall infarction with right ventricular involvement. Two hours after pain onset the patient was admitted to hospital in Bijeljina and sent to catheterisation laboratory straight after. All branches of left coronary artery were well visualized and without significant stenosis. Right coronary artery was occluded in proximal segment. Predilatation was performed with SC Sprinter legend 2,0x20mm balloon. After predilatation thrombus burden is still large, blood flow was slow with significant residual stenosis. Than, BMS Pro-kinetic energy 3,5x20mm stent was implanted. After stent implantation thrombus burden existed and there was no flow in PLV branch. Thrombus mass was 2 cm long and successfully aspirated with Export aspiration catheter. Control coronarography showed no residual stenosis and normal blood flow was restored through branches of right coronary artery. Conclusion. Procedure must be gradual, carefully planned and aspiration of thrombus should be taken only after initial balloon angioplasty with flow evaluation. Large thrombus burden or several smaller thrombi with clear flow obstruction and poor peripheral flow could be the reason for aspiration of thrombus along with possible intracoronary administration of GP IIbIIIa inhibitors. If conducted cautiously, aspiration of thrombus may still be considered as a valuable technique in selected patients with a large angiographic thrombus burden.

The REFLO-STEMI (REperfusion Facilitated by LOcal adjunctive therapy in ST-Elevation Myocardial Infarction) trial: a randomised controlled trial comparing intracoronary administration of adenosine or sodium nitroprusside with control for attenuation of microvascular obstruction during primary percutaneous coronary intervention

BackgroundMicrovascular obstruction (MVO) predicts short- and longer-term outcomes following primary percutaneous coronary intervention (PPCI) treatment of ST-elevation myocardial infarction (STEMI). The evidence base supporting the role of adenosine and sodium nitroprusside (SNP), the most evaluated adjunctive therapies aimed at attenuating MVO and infarct size, remains weak as the trials involved have had variable end points and used differing drug doses and modes of delivery.ObjectiveTo determine whether intracoronary administration of adenosine or SNP following thrombus aspiration reduces infarct size and/or MVO measured by cardiac magnetic resonance (CMR) imaging in patients undergoing PPCI within 6 hours of onset of STEMI.DesignMulticentre, prospective, parallel, randomised controlled and open-label trial with blinded end point analysis.SettingFour high-volume UK PPCI centres.ParticipantsPatients with STEMI undergoing PPCI with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0/1 in the infarct-related artery and no significant bystander coronary artery disease on angiography.InterventionsParticipants were anticoagulated with bivalirudin and allocated by an automated 24-hour telephone randomisation service to one of three groups: (1) standard PPCI (control), (2) PPCI with adjunctive adenosine 1–2 mg or (3) PPCI with adjunctive SNP 250 µg. The study drugs were delivered intracoronary immediately following thrombus aspiration and again following successful stenting.Main outcome measuresThe primary outcome was infarct size (% total left ventricular end-diastolic mass; %LVM) measured by CMR imaging undertaken 48–96 hours post PPCI. Secondary outcome measures included MVO (hypoenhancement within the infarct core) on CMR imaging, electrocardiographic and angiographic markers of microvascular perfusion and major adverse cardiac events (MACEs) during a median of 6 months’ follow-up. The study aimed to recruit 240 patients (powered at 80% to detect a 5% absolute reduction in infarct size).ResultsThe trial completed recruitment in April 2014 having randomised 247 patients (standard PPCI group,n = 86; PPCI + adenosine group,n = 82; PPCI + SNP group,n = 79). In total, 79% of participants were male and the mean ± standard deviation age of participants was 59.3 ± 12.3 years. CMR imaging was completed in 197 (80%) patients (standard PPCI,n = 65; PPCI + adenosine,n = 63; PPCI + SNP,n = 69) for the primary outcome. There was no significant difference in infarct size [%LVM, median, interquartile range (IQR)] between the adenosine group (10.1, 4.7–16.2), the SNP group (10.0, 4.2–15.8) and the control group (8.3, 1.9–14.0) (p = 0.062 andp = 0.160 vs. control, respectively). MVO (%LVM, median, IQR) was similar across the groups [1.0, 0.0–3.7 (p = 0.205) and 0.6, 0.0–2.4 (p = 0.244) for adenosine and SNP, respectively, vs. 0.3, 0.0–2.8 for the control]. Using per-protocol analysis, infarct size (%LVM) was increased in adenosine-treated patients compared with control patients (12.0 vs. 8.3;p = 0.031). Increased left ventricular volume and reduced left ventricular ejection fraction were also observed in the adenosine arm. There was a significant increase in MACEs in patients undergoing adenosine-facilitated PPCI compared with control patients, driven by heart failure, at 30 days [hazard ratio (HR) 5.39, 95% confidence interval (CI) 1.18 to 24.60;p = 0.04] and 6 months (HR 6.53, 95% CI 1.46 to 29.2;p = 0.01) post randomisation.ConclusionsHigh-dose intracoronary adenosine and SNP during PPCI did not reduce infarct size or MVO measured by CMR imaging. Furthermore, adenosine may adversely affect mid-term clinical outcome and should not be used during PPCI to prevent reperfusion injury.Trial registrationClinicalTrials.gov NCT01747174 and EudraCT 2010–023211–34.FundingThis project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and NIHR partnership.

Evaluation of Short- and Long-Term Efficacy of Combined Intracoronary Administration of High-Dose Adenosine and Tirofiban during Primary Percutaneous Coronary Intervention.

To assess the influence of combined intracoronary application of high-dose adenosine and tirofiban in primary percutaneous coronary intervention (PCI) on clinical events and cardiac function. Our study evaluated consecutive patients with acute ST-segment elevation myocardial infarction undergoing primary PCI, who were randomly divided into adenosine group (n = 130) and control group (n = 128). Combined with thrombus aspiration and then intracoronary tirofiban, the adenosine group received intracoronary adenosine (2 mg) through the aspiration catheter 2 times. After thrombus aspiration and stenting of the infarct- related artery, the control group received placebo. The primary endpoint of our investigation was major adverse cardiac events (MACE) at the 1-year and 3-year marks. The secondary endpoint comprised left ventricular remodeling (LVR) at 6 months, myocardial blush grade (MBG), thrombolysis in myocardial infarction (TIMI) flow grade and corrected TIMI frame count (CTFC) after PCI. Our study found that TIMI flow grade post-PCI did not differ significantly between the 2 groups, while CTFC favored the adenosine-treated patients (21.6 ± 6.5 vs. 25.1 ± 7.8, p = 0.001). Although the adenosine group achieved a higher rate of MBG 3 (45.1% vs. 32.0%, p = 0.035) and MBG 2-3 (76.2% vs. 62.3%, p = 0.018) than the control group, the incidences of MACE at 1 year (20.0% vs. 25.0%, p = 0.373) and 3 years (26.9% vs. 32.0%, p = 0.413) were comparable. LVR occurred in 23.1% (27/117) of adenosine-treated patients and in 29.8% (43/114) of the controls (p = 0.296). Intracoronary administration of high-dose adenosine combined with intracoronary tirofiban and thrombus aspiration may further improve myocardial perfusion after primary PCI.

Cardiac N-methyl D-aspartate Receptors as a Pharmacological Target.

This study focuses on characterization of the cardiac N-methyl D-aspartate receptors (NMDARs) as a target for endogenous and synthetic agonists and antagonists. Using isolated perfused rat hearts, we have shown that intracoronary administration of the NMDAR agonists and antagonists has a pronounced effect on autonomous heart function. Perfusion of rat hearts with autologous blood supplemented with NMDAR agonists was associated with induction of tachycardia, sinus arrhythmia, and ischemia occurring within physiological plasma concentration range for glutamate and glycine. Intracoronary administration of the NMDAR antagonists exerted an antiarrhythmic effect and resulted in bradycardia and improvement of capillary perfusion. Action of antagonists eliprodil, Ro25-6981, memantine, ketamine, and MK-801 on autonomous heart function diverged strikingly from that of L-type Ca channel blockers. Cardiac NMDAR subunit composition differed from that of neuronal receptors and was age specific and chamber specific. Transcripts of the GluN3A and GluN2D were found in all heart chambers, whereas expression of GluN1 and GluN2A and 2C was restricted to the atria. Expression of the GluN2B protein in ventricles increased markedly with age of the animals. The obtained data reveal that NMDARs are expressed in rat heart contributing to the autonomic heart rate regulation and the function of the cardiac conduction system.

PCV18 - Lost in Translation: Randomised Controlled Trial and Systematic Review Evidence of Intracoronary Versus Intravenous Abciximab in St-Elevation Myocardial Infarction

Objectives: In the evaluation of healthcare interventions, systematic review and meta-analysis of randomized controlled trials (RCTs) has been regarded as the highest level of evidence. However, these methodologies have limitations that are inherent to potential bias and heterogeneity that may be present in the source data. In addition, meta-analyses can constitute a form of sequential analysis as in principle a new systematic review can be conducted each time trial is conducted. This study seeks to demonstrate the implications for the consideration of findings of statistical significance from meta-analysis via an examination of RCT and meta-analyses findings of intracoronary with intravenous abciximab in ST-elevation myocardial infarction (STEMI) patients. Methods: A systematic review of RCTs and meta-analyses. Data on mortality were pooled using: (1) cumulative meta-analysis, which does not take into consideration potential false-positive findings ude to repeatd significance tests as new trials are addded; and (2) sequentail meta-analysis, which allows for the possibility that the meta-analysis was repeated after each trial was published. Results: To date, the efficacy and safety of intracoronary versus intravenous administration of abciximab in STEMI patients has been evaluated in eight RCTs, and ten systematic reviews and meta-analyses. None of the trials, with the exception of one, reported significant benefits associated with intracoronary abciximab; this is consistent with the findings reported by a recent large trial. Metaanalyses carried out prior to the publication of this recent trial showed contrasting results. However, the sequential analysis did not indicate a statistically significant reduction in mortality at any point. Conclusions: It is also important to take into account the essentially sequential nature of the meta-analysis. The total number of trial that will be conducted is not fixed, and we should allow for the fact that multiple meta-analyses may be conducted, although not always reported, as trials are conducted.

Apport de l’administration intracoronaire d’antithrombotiques par cathéter à ballon de perfusion en phase aiguë d’infarctus du myocarde avec thrombus massif et échec de la thromboaspiration

BackgroundMassive intracoronary thrombus is associated with adverse procedural results including failed aspiration and unfavourable reperfusion. We aim to evaluate the effect of the intracoronary administration of antithrombotic agents via a perfusion catheter in patients with ST-segment elevation myocardial infarction (STEMI) presenting with a large thrombus burden and failed aspiration. MethodsWe retrospectively analyzed the thrombus burden, the TIMI grade flow, and the myocardial Blush in 25 consecutive STEMI patients with a large thrombus burden and failed manual aspiration, who received intracoronary infusion of glycoprotein IIb/IIIa inhibitors (N=17) or bivalirudine (N=8) via a 6F-infusion catheter (ClearWay™ RX) ResultsMean age was 67±14 years, 16 patients (64 %) presented with anterior STEMI, and 7 (28 %) with cardiogenic shock. Immediately after intracoronary infusion, the TIMI flow grade improved of 2 grades in 7 patients (28 %), and 1 grade in 14 (56 %), a complete resolution of the thrombus was observed in 9 patients, and a >50 % resolution in 12. Blush was improved of 3 grades in 15 patients (60 %), of 2 grades in 7 (28 %), and Blush grade 0 remained in 3. At the end of procedure, we observed normal TIMI 3flow in most patients (92 %), a complete resolution of thrombus in 80 %, and a Blush grade 3 in 68 %. ConclusionsIn STEMI patients presenting with a large thrombus burden and failed aspiration, intracoronary administration of glycoprotein IIb/IIIa inhibitors or bivalirudin via the perfusion catheter ClearWay™ RX significantly reduced the thrombus burden and improved the TIMI flow and the Blush grade, without bleeding.

Cardioprotective effects of intracoronary administration of 4-chlorodiazepam in small and large animal models of ischemia-reperfusion

BackgroundThe Translocator Protein (TSPO) of the mitochondrial membrane has been recognized as a potential therapeutic target for mitigation of myocardial ischemia-reperfusion injury. Administration of 4-chlorodiazepam (4-CLD), a TSPO ligand, has been shown to confer acute cardioprotective effects in small animals; however, long-term studies and studies in clinically-relevant large animal models are lacking. In the present study we investigated a potential cardioprotective effect of intracoronary administration of 4-CLD in small and large animal models of ischemia-reperfusion. MethodsAcute myocardial infarction was induced in 38 Wistar rats and 29 farm pigs by ligation of the left anterior descending coronary artery, followed by reperfusion. Animals were randomized to undergo intracoronary infusion of 2μM 4-CLD or vehicle just prior (pigs) or immediately after (rats) reperfusion. Infarcted rats were euthanized either after 1h of reperfusion (for histological assessment of the “no reflow” area) or after 60days (for serial evaluation of cardiac function and structure by echocardiography and assessment of infarct size). Infarcted pigs were euthanized after 2h of reperfusion for histological assessment of infarct size and “no reflow” area. ResultsIn infarcted rats, intracoronary infusion of 4-CLD resulted in acute reduction of the “no reflow” area and conferred durable long-term structural and functional benefits (reduction in infarct size, attenuation of adverse remodeling, improvement in global systolic function). In infarcted pigs, intracoronary infusion of 4-CLD was well-tolerated from a hemodynamic standpoint and resulted in acute reduction in infarct size, reduction in “no reflow” area and more rapid resolution of ST-segment elevation. ConclusionsIn a rat model of myocardial infarction, intracoronary administration of 4-CLD attenuated the “no reflow” phenomenon and produced long-term structural and functional benefits. In a porcine model of myocardial infarction intracoronary administration of 4-CLD did not raise safety concerns and conferred acute cardioprotective effects.

Abstract P239: Papaverine-induced Ventricular Fibrillation Developing During Coronary Flow Reserve Studies

Background: Estimation of the fractional flow reserve (FFR) is considered to be an established method by which to assess stable coronary artery stenosis. Induction of maximal coronary hyperemia is important during FFR. Papaverine is often used to achieve maximal hyperemia. However, this drug has been reported to increase the risk of ventricular arrhythmias. The purpose of the present study was to discover predictors of papaverine-induced ventricular fibrillation (VF) developing during FFR. Methods: A total of 187 clinically stable patients were included in the study. FFR was performed to evaluate lesions for which percutaneous coronary intervention (PCI) was to be considered after coronary angiography. FFRs were determined after intracoronary papaverine administration (12 mg into the left and 8 mg into the right coronary arteries). We compared patients in whom VF did and did not develop in terms of clinical and ECG characteristics. Results: We performed FFR on 214 lesions (112 in the left anterior descending arteries, 38 in the left circumflex arteries, and 64 in the right coronary arteries) of 187 patients. The average patient age was 72.5 ± 10 years. We found that the QTc interval was prolonged in all patients after papaverine administration (average post-administration QTc interval = 569 ± 89 ms; average ΔQTc interval = 144 ± 80 ms). VF developed in three patients with significantly prolonged QT intervals (average post-administration QTc interval = 639 ± 19 ms, average ΔQTc interval = 220 ± 64 ms, p < 0.02) and all of them occurred after administration of papaverine into the left coronary artery. Three-vessel disease was significantly predictive of VF (p < 0.003). In the three-vessel group, the complications of low left ventricular function (ejection fraction<50%), hypokalemia (serum K <3.5 mEp/L), and bradycardia (<50 beats/min), were significantly associated with VF (p < 0.045). Conclusions: Three-vessel disease is a predictor of the development of VF during FFR performed with the aid of papaverine, especially if accompanied by one or more of low left ventricular function, hypokalemia, or bradycardia.

Intracoronary Bivalirudin Bolus in ST-Elevation Myocardial Infarction Patients Treated with Primary Angioplasty: Theoretical Bases, Clinical Experience, and Future Applications.

Intracoronary thrombus is a common finding in acute coronary syndromes and often correlates with adverse prognosis and complications during percutaneous coronary interventions (PCIs). Bivalirudin, a direct thrombin inhibitor, is one of the recommended antithrombotic treatments for PCI in ST-elevation myocardial infarction (STEMI). The intracoronary administration of a bivalirudin loading dose, even if off-label, offers theoretical advantages over the standard intravenous route, providing a very high drug concentration in the infarct-related artery without increasing the total dose of the drug administered. After the description in case reports of such an approach, a larger scale experience was recently reported in a large cohort of patients with STEMI treated during primary PCI with a bivalirudin intracoronary loading dose followed by the standard intravenous maintenance infusion. As a control group, a propensity score-matched cohort of patients undergoing primary PCI treated with intravenous bivalirudin in the same institution was selected. Compared with the intravenous bolus, the intracoronary administration of bivalirudin was associated with improved ST-segment resolution, lower post-procedural peak CK-MB levels, and better Thrombolysis in Myocardial Infarction (TIMI) frame count values, without difference in bleeding rates. Thus, this new promising antithrombotic strategy, based on the intracoronary administration of a bivalirudin loading dose during primary PCI, appeared safe, improved myocardial reperfusion, and mitigated enzymatic myocardial infarct size compared with the standard intravenous protocol. Randomized trials are warranted to confirm these results and evaluate the possible long-term clinical benefits.

Efficacy and Safety of Thrombectomy Combined with Intracoronary Administration of Tirofiban in ST-segment Elevation Myocardial Infarction (STEMI).

BackgroundNo/slow reflow gives rise to serious complications in STEMI patients undergoing PCI, and can lead to worse outcomes. Several measures are used to prevent no/slow reflow, including thrombus removal processes and intensive use of anticoagulant agents. Our study was designed to evaluate the efficacy and safety of thrombectomy and intracoronary administration of GPIIb/IIIa inhibitors in STEMI patients undergoing PPCI.Material/MethodsWe randomly assigned 240 STEMI patients into 3 groups. Before PPCI, patients in group A received thrombectomy and intracoronary administration of tirofiban. Patients in group B received thrombectomy, and patients in group C neither of these 2 treatments. Their demographic data and coronary angiography results were recorded. TIMI grade flow was used to evaluate the effect. After the follow-up, major adverse cardiac events were regarded as study endpoints in evaluating the safety of the combined therapy.ResultsWe found no significant differences among the 3 groups in demographic and clinical characteristics (p>0.05). Patients in group A had better TIMI grade classifications and ST-segment elevation (p=0.005), and lower incidence of no/slow reflow (p=0.031) and MACE. During 6-month follow-up, the MACE rate was lower in group A than in groups B and C (p=0.038).ConclusionsThe use of thrombectomy combined with intracoronary administration of tirofiban is relatively effective and safe in STEMI patients undergoing PPCI.

Effects of intracoronary administration of tirofiban in the patients with acute myocardial infarction that had no reflow phenomenon of infarct related artery(IRA)after primary percutaneous transluminal coronary intervention

Effects of intracoronary administration of tirofiban in the patients with acute myocardial infarction that had no reflow phenomenon of infarct related artery(IRA)after primary percutaneous transluminal coronary intervention

Intracoronary administration of different doses of anisodamine in primary percutaneous coronary intervention: protective effect in patients with ST-segment elevation myocardial infarction.

The aim of this study was to evaluate the effects of intracoronary administration of anisodamine on myocardial reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) undergoing a primary percutaneous coronary intervention (pPCI). Patients with acute STEMI undergoing pPCI were enrolled in this randomized-controlled study (January 2014-June 2015) and divided randomly into four groups: group A (normal saline), group B (1000 μg anisodamine), group C (2000 μg anisodamine), and group D (4000 μg anisodamine). The study group included 140 patients. Percentages of thrombolysis in myocardial infarction (TIMI) myocardial perfusion grade 3, increased values of TIMI myocardial perfusion grade after stenting, and decreased values of corrected TIMI frame count in groups B, C, and D were all significantly higher than those in group A (P=0.031, 0.027, 0.003, and P<0.001, respectively). TIMI frame count after stenting in groups B, C, and D was significantly lower than that in group A (P=0.001). Left ventricular ejection fraction at 1 week after pPCI and at the 3-month follow-up, as well as the major adverse cardiac event-free survival rate in groups B, C, and D were higher than those in group A (P=0.027, 0.016, and 0.019, respectively). Intracoronary administration of anisodamine at different doses improved myocardial reperfusion in patients with STEMI undergoing pPCI and reduced major adverse cardiac events. The protective effect of anisodamine at a dose of 4000 μg might be better than the doses at 1000 and 2000 μg.

Effect of intracoronary tirofiban bolus administration on platelet-derived microparticles and short-term clinical benefit in patients with acute ST-segment elevation myocardial infarction

Objective To investigate the effect of intracoronary tirofiban bolus administration on platelet-derived microparticles (PMPs) and its correlation with the short-term clinical benefit in patients with acute ST-segment elevation myocardial infarction (ASTEMI) undergoing emergency percutaneous coronary intervention (PCI). Methods A total of 90 patients with ASTEMI undergoing emergency PCI were selected and randomized into the intracoronary group (intracoronary tirofiban 10.00 μg/kg bolus within 1-3 min followed by intravenous continuous infusion at 0.15 μg·kg-1·min-1 for 36 h, n=30), intravenous group (intravenous tirofiban 10.00 μg/kg bolus within 1-3 min followed by intravenous continuous infusion at 0.15 μg·kg-1·min-1 for 36 h, n=30) and control group (without tirofiban administration, n=30). The 3 ml blood samples from coronary artery were obtained before and 10 min after tirofiban infusion. The 3 ml blood samples from radial artery were collected 24 hours after tirofiban infusion and 12 hours after drug withdrawal. The counts of PMPs were analyzed by flow cytometry. The thrombolysis in myocardial infarction (TIMI) flow grade classification and TIMI Myocardial Perfusion Grade in the culprit blood vessel after PCI, and the incidences of bleeding and major adverse cardiac events (MACE) within 30 days after surgery were recorded. Results There was no significant difference in baseline of PMPs among intracoronary group, intravenous group and control group (all P>0.05). The level of PMPs was decreased in the intracoronary and intravenous group as compared with the control group 〔(3.6±2.3)%, (5.1±2.7)% vs. (6.7±3.2)%, P 0.05), and PMPs levels were lower in intracoronary and intravenous group than in control group (both P 0.05). Immediately after PCI, the TIMI flow grade and TIMI myocardial perfusion grade in the culprit blood vessel in intracoronary group were superior to those in the intravenous group and control group (P 0.05). Conclusions The intracoronary versus intravenous tirofiban administration can effectively and immediately reduce the number of PMPs in patients with acute ST-segment elevation myocardial infarction undergoing emergency interventional treatment, quickly inhibit the activated platelets, and decrease the total major adverse cardiovascular events without increasing the risk of bleeding. Key words: Myocardial infarction; Blood platelets; Angioplasty, intervention, percutaneous coronary

The role of ADAMTS13 in acute myocardial infarction: cause or consequence?

AimsADAMTS13, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13, is a metalloprotease that cleaves von Willebrand factor (VWF). There is considerable evidence that VWF levels increase and ADAMTS13 levels decrease in ST-elevation myocardial infarction (STEMI) patients. It is unclear whether this contributes to no reflow, infarct size, and intramyocardial haemorrhage (IMH). We aimed to determine the role of ADAMTS13 in STEMI patients and to investigate the benefits of recombinant ADAMTS13 (rADAMTS13) in a porcine model of myocardial ischaemia-reperfusion.Methods and resultsIn 49 consecutive percutaneous coronary intervention (PCI)-treated STEMI patients, blood samples were collected directly after through 7 days following PCI. Cardiac magnetic resonance was performed 4–6 days after PCI to determine infarct size and IMH. In 23 Yorkshire swine, the circumflex coronary artery was occluded for 75 min. rADAMTS13 or vehicle was administered intracoronary following reperfusion. Myocardial injury and infarct characteristics were assessed using cardiac enzymes, ECG, and histopathology. In patients with IMH, VWF activity and VWF antigen were significantly elevated directly after PCI and for all subsequent measurements, and ADAMTS13 activity significantly decreased at 4 and 7 days following PCI, in comparison with patients without IMH. VWF activity and ADAMTS13 activity were not related to infarct size. In rADAMTS13-treated animals, no differences in infarct size, IMH, or formation of microthrombi were witnessed compared with controls.ConclusionsNo correlation was found between VWF/ADAMTS13 and infarct size in patients. However, patients suffering from IMH had significantly higher VWF activity and lower ADAMTS13 activity. Intracoronary administration of rADAMTS13 did not decrease infarct size or IMH in a porcine model of myocardial ischaemia-reperfusion. These data dispute the imbalance in ADAMTS13 and VWF as the cause of no reflow.

Abstract 525: Cases with Uncommon Anti-phospholipid Antibody Syndrome Developed Multifocal Vascular Disorders Such as Ischemic Enteritis, Portal Vein Thrombosis, Ischemic Heart Disease and Cerebral Infarction

Purpose: We report cases with uncommon anti-phosholipid antibody syndrome developed ischemic enteritis, portal vein thrombosis, ischemic heart disease and cerebral infarction. The difficulty in diagnosing and treatment procedures for multifocal vascular disorders is discussed. Patients and Methods: Patient 1, 76-year-old man, with acute abdomen. Patient 2, 54-year-old man, with intractable esophageal varices. Clinical manifestation was superior mesenteric artery (SMA) thrombosis in the patient 1 and portal vein thrombosis in the patient 2. Serial CT scans were examined on 64 or 80 multidetector-row CT (Toshiba), with bolus injection of contrast media for CT angiography (CTA). Abdominal angiography with endovascular intervention and coronary angiography were performed on Allura Xper FD-20 and FD-10 (Philips). Results: Emergency CTA of patient 1 showed decreased contrast enhancement of SMA and SMV but enhancement of intestinal walls were well preserved. Although the patient’s symptom got better, follow-up CT revealed the growth of SMA thrombosis. The aspiration and the dissolution of SMA thrombosis were performed through the SMA catheter for five days resulted in complete recanalization.Then he felt chest oppression and 75% stenosis of RCA segment 4, followed by complete spastic occlusion on Acetylcholine loading on the coronary angiography, which recovered perfectly with intra-coronary nitroglycerin administration. He discharged our hospital with health, while he had cerebellar infarction with right cerebellar artery occlusion. On patient 2, to resolve portal hypertension, balloon-occluded retrograde transvenous obliteration was scheduled, however, due to numerous collaterals prevented the effective venous obliteration and splenic arterial embolization was selected alternatively. Discussion and Conclusions: The progressive SMA thrombosis with coronary disease and subsequent cerebellar occlusion seen in patient 1, and the portal vein thrombosis in patient 2 without chronic hepatitis nor cirrhosis were unusual. To discover underlining uncommon anti-phosholipid antibody syndrome is important to prevent serious vascular diseases in sequence.

Moderate vasomotor response to acetylcholine provocation test as an indicator of long-term prognosis.

The acetylcholine (ACh) provocation test (ACh-test) is used for the diagnosis of vasospastic angina (VSA). However, subjects often show a moderate spasm (MS) response for which diagnosis of VSA is not definitive, and the clinical significance of this response is unknown. We assessed moderate coronary vasomotor response to the ACh test as an indicator of long-term prognosis. A total of 298 consecutive patients who underwent the ACh test for suspected VSA were retrospectively investigated. Coronary spasm severity after intracoronary administration of isosorbide dinitrate was evaluated by measuring epicardial coronary artery diameter reduction after ACh injection. Patients were divided into three groups according to the diameter reduction during the ACh test: severe spasm (SS) showing ≥75% diameter reduction, MS showing ≥50% diameter reduction, and others (N). In Kaplan-Meier analysis, the major adverse cardiac event (MACE) rates with a median follow-up of 4.6years were significantly worse in SS (11.1%) and MS (8.5%) than N (1.9%), (SS vs N; P=0.009, MS vs N; P=0.029). Significant difference in MACE rates was not observed between SS and MS (P=0.534). Cox regression analysis revealed that MS remained an independent predictor of MACE after adjustment for other confounders (HR: 7.18, 95% CI 1.42-36.4, P=0.017). Patients with MS by ACh test had a cardiac event rate comparable with that of patients with SS and significantly worse than that of patients with normal vasomotor responses.

Impact of additional intracoronary nicorandil administration during fractional flow reserve measurement with intravenous adenosine 5′-triphosphate infusion

BackgroundFractional flow reserve (FFR) is a useful index for determining the functional severity of epicardial coronary artery stenosis as an invasive physiological method. Although intravenous adenosine 5′-triphosphate (ATP) is generally used as a hyperemic agent for FFR measurement in Japan, there are some concerns about the variability of FFR measurement (short half-life, effect of caffeine, cyclic change). It is difficult to confirm sufficient maximum hyperemia after ATP infusion. Recent studies reported that nicorandil (NIC) could be an alternative to ATP as a hyperemic agent. MethodsPatients who underwent FFR assessments of angiographically intermediate lesions were included. All patients were asked to refrain from caffeine-containing products more than 12hours before FFR measurements. All patients first received intravenous (IV) ATP infusion (180μg/kg/min) for 3min to measure FFR (ATP-FFR). After additional intracoronary (IC) NIC administration (2mg/30s) during ATP infusion, FFR was measured again (NIC-FFR). To check cyclic change in FFR, we measured minimum and maximum FFR values during both ATP and NIC hyperemic phase. ResultsIn this study, 94 patients with 94 lesions were enrolled. Mean FFR value was 0.81±0.10 in ATP-FFR infusion and 0.80±0.09 in NIC-FFR, respectively. ATP-FFR and NIC-FFR had a strong correlation on the whole (r=0.92, p<0.001). In 18 patients (19%), FFR values were significantly lower in NIC-FFR than in ATP-FFR. In one-third of those patients (6%), it was possible to change therapeutic strategy from deferral range (>0.80) to interventional range (≦0.80) after NIC-FFR measurements. Cyclic change in FFR was smaller in NIC-FFR than in ATP-FFR (0.03±0.02 vs. 0.06±0.05, p<0.0001). ConclusionAdditional IC NIC might be useful to confirm sufficient maximum hyperemia after IV ATP infusion in daily clinical practice. Furthermore, IC NIC could reduce cyclic change in FFR; thus, physicians might find it easier to determine FFR value during the procedure.

Pulse waveform analysis in the optic nerve head circulation reflects systemic vascular resistance obtained via a Swan-Ganz catheter.

To determine whether a pulse waveform analysis in the optic nerve head (ONH) circulation as determined by laser speckle flowgraphy (LSFG) can provide systemic hemodynamic values - the systemic vascular resistance (SVR) in particular - similar to those obtained by using a Swan-Ganz catheter, which is an invasive method. Sixteen consecutive subjects were examined. Hemodynamic monitoring was obtained from right heart catheterization with a Swan-Ganz catheter and coronary angiography without an intracoronary nitroglycerin administration. Direct blood pressure was measured with a trans-radial approach. Single regression analyses were used to determine the relationship between the blowout score and blowout time, which are the items of the pulse waveform analysis in the ONH, by using LSFG and the hemodynamic parameters. The blowout time was significantly and negatively correlated with the SVR (r = -0.52, p = 0.04), the ocular perfusion pressure with the mean arterial blood pressure of the radial artery (r = -0.52, p = 0.04) and the radial artery pulse pressure (r = -0.52, p = 0.04).The pulmonary capillary wedge pressure (r = -0.44, p = 0.09) and the mean arterial blood pressure of the radial artery (r = -0.44, p = 0.09) tended to be correlated with the blowout time, but did not reach significance. The blowout score was significantly and negatively correlated with the radial artery blood pressure (r = -0.51, p = 0.046). A pulse waveform analysis in the ONH by LSFG may be one of the useful methods for understanding the SVR.