Ticagrelor versus clopidogrel for recovery of vascular function immediately after successful chronic coronary total occlusion recanalization: A randomized clinical trial.

Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor. We sought if ticagrelor may augment adenosine-induced coronary blood flow vs. clopidogrel immediately after successful CTO percutaneous coronary intervention (PCI).

Revascularization vs. Medical Therapy for Coronary Chronic Total Occlusions in Patients With Chronic Kidney Disease.

BACKGROUND: We investigated whether the outcome of revascularization differed from the outcome of medical therapy in chronic kidney disease (CKD) and non-CKD patients with chronic total occlusion (CTO).Methods and Results:A total of 2,010 patients with CTO who underwent revascularization (n=1,355), including percutaneous coronary intervention (n=878) and coronary artery bypass grafting (n=477), or had medical therapy alone (n=655) were examined. The primary outcome was all-cause death during follow-up. Among the non-CKD patients (n=1,679), revascularization had a lower incidence of all-cause death (adjusted hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.41-0.72, P<0.001) compared with medical therapy. Among the CKD patients (n=331), the difference in the incidence of all-cause death was not as marked between the 2 treatments (adjusted HR 0.71, 95% CI 0.48-1.06, P=0.09). There was a significant interaction between kidney function and treatment strategy (revascularization vs. medical therapy) on all-cause death (P for interaction=0.014). CONCLUSIONS: Based on the clinical outcomes, in CTO patients with preexisting CKD, revascularization via PCI or bypass surgery might not be as effective as in non-CKD patients.

Characteristics of dyspnoea and associated clinical outcomes in the CHAMPION PHOENIX study.

Dyspnoea may be induced by some reversibly-binding P2Y12 inhibitors, including cangrelor and ticagrelor. Dyspnoea was not associated with any compromise to the efficacy of ticagrelor in the PLATO study. The CHAMPION PHOENIX study (NCT01156571) compared initial treatment with cangrelor versus initial treatment with clopidogrel in patients undergoing PCI. We investigated the incidence, characteristics, and associated clinical outcomes in patients with dyspnoea in CHAMPION PHOENIX. Adverse events (AEs) of dyspnoea to 48 hours were recorded in patients randomised to cangrelor or clopidogrel in CHAMPION PHOENIX. The composite primary endpoint of death, myocardial infarction, ischaemia-driven revascularisation, or stent thrombosis as well its individual components were assessed in patients who did or did not report dyspnoea. A total of 68 (1.2 %) cangrelor-treated patients and 18 (0.3 %) clopidogrel-treated patients reported dyspnoea (p<0.001). Most dyspnoea events in cangrelor-treated patients were considered mild (71 %) or moderate (28 %) and only one event was considered severe and led to discontinuation of cangrelor. The dyspnoea events in the clopidogrel-treated patients were mild (78 %) or moderate (22 %). Characteristics of dyspnoea were consistent with those seen in the CHAMPION programme as a whole. In the modified intention-to-treat population, rates of the composite primary outcome and its individual components were not affected by the presence of dyspnoea in cangrelor-treated patients. Cangrelor-related dyspnoea is transient, usually mild or moderate, and unlikely to lead to discontinuation of therapy. The occurrence of dyspnoea does not seem to be associated with any reduction in the efficacy of cangrelor compared with clopidogrel as initial therapy in PCI patients.

Association of ß-blocker therapy with long-term clinical outcomes in patients with coronary chronic total occlusion.

There are limited data regarding the efficacy of ß-blockers for secondary prevention in patients with coronary chronic total occlusion (CTO). Therefore, we investigated the association of ß-blocker therapy with long-term clinical outcomes in CTO patients. From March 2003 to February 2012, a total of 2024 CTO patients treated with either medical therapy alone or revascularization were enrolled in the study. We assessed 1596 patients with stable ischemic heart disease and divided them into the ß-blocker group (n = 932) and the no-ß-blocker group (n = 664). The primary outcome was all-cause death. The median follow-up duration was 3.9 (interquartile range: 2.0-6.2) years. All-cause death occurred in 11.6% patients in the ß-blocker group and 13.6% patients in the no-ß-blocker group (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.61-1.08; P = 0.15). In the propensity score-matched population (570 pairs), all-cause death occurred in 12.3% patients in the ß-blocker group and 12.8% patients in the no-ß-blocker group (HR: 0.93, 95% CI: 0.67-1.29; P = 0.66). In subgroup analysis, ß-blocker therapy was associated with better outcome, in terms of all-cause death, in patients with CTO of the left anterior descending coronary artery and Synergy Between PCI with Taxus and Cardiac Surgery (SYNTAX) score ≥23 (P for interaction = 0.01 and 0.02, respectively). In conclusion, ß-blocker therapy was not associated with favorable long-term clinical outcomes in stable CTO patients, regardless of treatment strategy. However, ß-blocker therapy might be beneficial in a highly selective group of CTO patients with a high ischemic burden.

Effect of Qi-regulating,Phlegm-resolving,and Blood-promoting Prescription on Rat Coronary Microvascular Thrombosis and Coronary Microvascular Occlusion.

Objective To explore the effect of qi-regulating,phlegm-resolving,and blood-promoting prescription on coronary microvascular thrombosis and coronary microvascular occlusion in rat models. Methods Totally 125 healthy clean-grade male SD rats weighing (300±25) g were sequentially numbered and then randomly divided into treatment group (n=60),control group (n=60) and blank group (n=5).Rats in the treatment group and control group received apical left ventricular injection of sodium laurate to establish rat models of coronary microvascular thrombosis. Then,rats in the control group were given distilled water by gavage one day before operation and after surgery. In contrast,rats in the treatment group were given qi-regulating,phlegm-resolving,and blood-promoting prescription by gavage one day before operation and after surgery. Five rats from both treatment group and control group were killed at each of six time points (1 hour,24th hour,7th day,14th day,21th day,and 28th day),and the myocardium specimens were harvested. The 5 rats in the blank group did not receive any special treatment and were given normal feeding;in the 28th day,they were sacrificed to obtain the myocardial specimens. Pathological sections of rat myocardial tissues were made to observe and compare the degrees of coronary microvascular thrombosis and coronary microvascular obstruction.Results In the treatment group and the control group,coronary microvascular thrombosis occurred 1 hour after apical sodium laurate injection and reached the peak at the 24th hour. Compared with the blank group,the treatment group and the control group showed different degree of coronary microvascular obstruction. Comparison between the treatment group and the control group at each time point showed that the coronary microvascular thrombosis in the treatment group was significantly lower than that in the control group (P<0.05 or P<0.01).The severity of coronary microvascular occlusion was significantly milder in the treatment group than in the control group (P<0.05 or P<0.01).Conclusions Apical left ventricular injection of sodium laurate successfully established rat models of coronary microvascular thrombosis. Qi-regulating,phlegm-resolving,and blood-promoting prescription can reduce coronary microvascular thrombosis and improve coronary microvascular obstruction.

Clinical outcomes of multiple chronic total occlusions in coronary arteries according to three therapeutic strategies: Bypass surgery, percutaneous intervention and medication.

BACKGROUND: Limited data exist regarding clinical outcomes of multiple chronic total occlusions (CTOs) according to therapeutic strategies, coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), and medical treatment (MT). METHODS: From March 2003 to February 2012, a total of 2024 patients with at least one CTO were enrolled in retrospective, single-center registry. 393 patients with at least two CTOs were categorized based on the intention-to-treat principle. Propensity-score matching was performed. The primary outcome was major adverse cardiac and cerebral events (MACCE). RESULTS: Of 393 patients with multiple CTOs, 169 patients (43%) were referred for CABG, 130 (33%) for PCI, and 94 (24%) for MT. Median overall follow-up duration was 46.5 (interquartile range 22.7 to 74.6) months. After propensity-score matching analysis, CABG had lower rates of MACCE when compared with PCI (HR=0.43, 0.21-0.85, P=0.01) and MT (HR=0.10, 0.04-0.27, P<0.01). Rates of repeat revascularization was significantly lower in CABG, compared with PCI (HR=0.05, 0.01-0.40, P<0.01) and MT (HR=0.01, 0.00-0.54, P=0.02). CABG had similar rates of cardiac death compared with PCI group (HR=0.97, 0.37-2.53, P=0.95), but had significantly lower rates of cardiac death compared with MT (HR=0.24, 0.08-0.75, P=0.01). CONCLUSIONS: For management of multiple CTOs, MT alone was associated with higher incidence of cardiac death and MACCE compared with CABG. PCI was associated with higher incidence of MACCE, as driven by higher repeat revascularization rate. These findings suggest that CABG might be associated with better clinical outcome and considered as the preferred treatment strategy in patients with multiple CTOs.

Three-year clinical outcome in the Primary Stenting of Totally Occluded Native Coronary Arteries III (PRISON III) trial: a randomised comparison between sirolimus-eluting stent implantation and zotarolimus-eluting stent implantation for the treatment of total coronary occlusions.

AIMS: Sirolimus-eluting stents (SES) have been shown to be superior to Endeavor zotarolimus-eluting stents (ZES) and comparable to Resolute ZES at eight-month angiography in patients treated for total coronary occlusions (TCO). This study investigated clinical outcome at three-year follow-up. METHODS AND RESULTS: The PRISON III trial investigated the efficacy and safety of SES against ZES (Endeavor and Resolute) in two study phases. In the first phase, 51 patients were randomised to receive SES and 46 to Endeavor ZES. In the second phase, 103 and 104 patients were randomised to SES or Resolute ZES, respectively. Between one and three years there were only a few additional clinical events in all groups. As a result, the rates of target lesion revascularisation 12.2% vs. 19.6%, p=0.49, target vessel failure 14.3% vs. 19.6%, p=0.68, and definite or probable stent thrombosis 4.1% vs. 2.2% were comparable between SES and Endeavor ZES at three years. In the second study phase, the rates of target lesion revascularisation 10% vs. 5.9%, p=0.42, target vessel failure 10% vs. 7.9%, p=0.79 and definite or probable stent thrombosis 1.0% vs. 0% were similar between SES and Resolute ZES. CONCLUSIONS: The present study demonstrated a low incidence of clinical events between one- and three-year follow-up with either SES compared to Endeavor ZES or SES versus Resolute ZES in patients treated for total coronary occlusions.

Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion

The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in rabbits. No-reflow was not dependent on the reduction of infarct size.

Effects of single-dose atorvastatin on interleukin-6, interferon gamma, and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion.

The mechanisms of statins relieving the no-reflow phenomenon and the effects of single-dose statins on it are not well known. This study sought to investigate the effects of inflammation on the no-reflow phenomenon in a rabbit model of acute myocardial infarction and reperfusion (AMI/R) and to evaluate the effects of single-dose atorvastatin on inflammation and myocardial no-reflow. Twenty-four New Zealand white male rabbits (5-6 months old) were randomized to three groups of eight: a sham-operated group, an AMI/R group, and an atorvastatin-treated group (10 mg/kg). Animals in the latter two groups were subjected to 4 h of coronary occlusion followed by 2 h of reperfusion. Serum levels of interleukin (IL)-6 were measured by enzyme-linked immunosorbent assay. The expression of interferon gamma (IFN-γ) in normal and infarcted (reflow and no-reflow) myocardial tissue was determined by immunohistochemical methods. The area of no-reflow and necrosis was evaluated pathologically. Levels of serum IL-6 were significantly lower in the atorvastatin group than in the AMI/R group (P<0.01). Expression of IFN-γ in infarcted reflow and no-reflow myocardial tissue was also significantly lower in the atorvastatin group than in the AMI/R group. The mean area of no-reflow [47.01% of ligation area (LA)] was significantly smaller in the atorvastatin group than in the AMI/R group (85.67% of LA; P<0.01). The necrosis area was also significantly smaller in the atorvastatin group (85.94% of LA) than in the AMI/R group (96.56% of LA; P<0.01). In a secondary analysis, rabbits in the atorvastatin and AMI/R groups were divided into two groups based on necrosis area (90% of LA): a small group (<90% of LA) and a large group (>90% of LA). There was no significant difference in the area of no-reflow between the small (61.40% of LA) and large groups (69.87% of LA; P>0.05). Single-dose atorvastatin protected against inflammation and myocardial no-reflow and reduced infarct size during AMI/R in rabbits. No-reflow was not dependent on the reduction of infarct size.

Riluzole reduces arrhythmias and myocardial damage induced by coronary occlusion in anaesthetized pigs.

The cardiac persistent sodium current (IN aP ) presents a novel target for cardiac ischaemic protection. Herein we investigated the effects of the IN aP blocker riluzole in a pig model of regional myocardial ischaemia. Landrace or Large White pigs were subjected to 3 h ligation of the left anterior descending coronary artery (LAD). Pigs received either saline (500 mL/h, i.v.) throughout the experiment (control; n = 7) or riluzole (2 mg/kg in 2 mL propylene glycol in 100 mL saline, i.v.; RIL; n = 7) between 15 and 5 min prior to ligation. The arrhythmia score was calculated in 5 min epochs. Myocardial damage was assessed using epicardial image analysis and histological sectioning. In the control group, all seven pigs developed premature ventricular contractions (PVC), seven developed non-sustained arrhythmias and six of seven developed sustained arrhythmias. Of the sustained arrhythmias, 23 of 28 instances were initiated by R-on-T extrasytoles (extrasystoles within the vulnerable period that can trigger re-entrant arrhythmias). In the RIL group, all seven pigs developed PVC, six of seven developed non-sustained arrhythmias and only three developed sustained arrhythmias, of which two of five instances were R-on-T initiated. The riluzole-treated pigs exhibited less myocardial damage than pigs in the control group (65% smaller surface area (P = 0.008) on gross epicardial inspection, 51% less oedema (P = 0.01), 53% less fibre waviness (P = 0.029) assessed by haematoxylin and eosin staining and 79% fewer fragmented nuclei (P = 0.009) assessed by terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling). In conclusion, riluzole significantly reduced Phase 2 (the period associated with irreversible damage) ischaemic R-on-T triggered and non-R-on-T arrhythmias and myocardial damage occurring during the 3 h period of regional ischaemia.

[The incidence of postoperative myocardial infarction and the left ventricular function in patients with type 2 diabetes mellitus after recanalization of chronic coronary occlusions].

AIM: To study the effects of intracoronary administration of the ischemic preconditioning (IP) trigger adenosine on the reduced incidence of percutaneous coronary intervention (PCI)-associated myocardial infarction (MI) and left ventricular (LV) systolic and contractile function in patients with type 2 diabetes mellitus (DM) during recanalization of chronic coronary occlusions (CCO). SUBJECTS AND METHODS: The patients were divided into 4 groups: 1) 45 patients without DM who received intracoronary placebo infusion; 2) 51 patients without DM who had 10 mg intracoronary adenosine during PCI; 3) 34 patients with type 2 DM who had intracoronary adenosine during PCI; 4) 37 with type 2 DM who received intracoronary placebo. Troponin I and the MB fraction of creatine phosphokinase were measured an hour before and 18-24 hours and 5 days after PCI. The authors estimated the incidence of PCI-associated MI according to the ESC/ACCF/AHA/WHF (2007) criteria and the time course of changes in LV ejection fraction (EF) and end-systolic volume (ESV) and end-diastolic volume, impaired LV local contractility index (ILVLCI) in 167 patients with CCO 1 day and 1 and 12 months after PCI. RESULTS: There was an improvement in myocardial systolic and contractile function after recanalization and stenting for CCO. The intracoronary adenosine groups showed significantly reduced incidence of PCI-associated MI, increased LV EF, and decreased LV ESV and ILVLCI as compared to the placebo groups. CONCLUSION: The intracoronary injection of the IP trigger adenosine is an effective and safe method to improve LV systolic and contractile function in patients with CCO and type 2 DM.

Management of extensive venous thrombosis following cardiac surgery in a patient with Behcet's disease.

Behçet's disease is a multisystemic vasculitis of unknown etiology, which is characterized by recurrent urogenital ulceration, cutaneous eruptions, ocular manifestations, arthritis and vasculitis, and its diagnosis is based on clinical criteria. Herein, we report a case of a patient with Behcet's disease, who was successfully managed with anticoagulant and anti-inflammatory therapy for disseminated venous thrombosis leading to pleural effusion, Budd-Chiari syndrome and central nervous system involvement following coronary artery bypass grafting surgery.

Endothelial and smooth muscle cells dysfunction distal to recanalized chronic total coronary occlusions and the relationship with the collateral connection grade.

OBJECTIVES: This study sought to assess the vascular function in patients with chronic total coronary occlusions (CTO) immediately after successful percutaneous recanalization and its relation with the pre-existing collateral circulation. BACKGROUND: CTOs represent a long-acting occlusion of a coronary vessel, in which the progressively developed collateral circulation may limit ischemia and symptoms. However, it is unknown if the coronary segment distal to the occlusion has a preserved vascular function. METHODS: We prospectively enrolled 19 consecutive patients, after percutaneous coronary intervention of a CTO. Luminal diameter, measured by quantitative coronary angiography, and coronary blood flow at level of epicardial coronary artery distal to the treated CTO was assessed before and after administration of acetylcholine (Ach), adenosine, and nitroglycerin (NTG). Collaterals were assessed angiographically by grading of Rentrop and of collateral connections (CC1: threadlike continuous connection; CC2: side branch-like connection). RESULTS: Overall, Ach and adenosine caused coronary artery vasoconstriction (p=0.001 and p=0.004, respectively), whereas NTG failed to induce vasodilation (p=0.084). Coronary blood flow significantly decreased with Ach (p=0.005), significantly increased with NTG (p=0.035), and did not change with adenosine (p=0.470). Patients with CC2 collaterals (n=8) had less vasoconstriction response and reduction in coronary blood flow after Ach (p=0.005 and p=0.008, respectively), and better vasomotor response to NTG (p=0.029) than patients with CC1 collaterals (n=11). CONCLUSIONS: Significant endothelial and smooth muscle dysfunction is present in the distal segments of successfully recanalized CTOs, and that seems to be more pronounced in the presence of a low grading of collateral circulation.

Selective blockade of P2Y12 receptors by prasugrel inhibits myocardial infarction induced by thrombotic coronary artery occlusion in rats.

We evaluated the effects of prasugrel, a third-generation thienopyridyl prodrug, on P2Y12 receptors, adenosine 5'-diphosphate (ADP)-induced platelet aggregation, and myocardial infarction (MI) in rats. Oral administration of prasugrel (0.3-3 mg/kg) resulted in the dose-related inhibition of washed platelet aggregation induced by ADP (1-10 µM). Ex vivo [H]-2-MeS-ADP binding to platelet P2Y12 receptors was also inhibited by prasugrel in a similar dose range. The antiaggregatory effects of prasugrel correlated strongly with P2Y12 blockade with correlation coefficients of 0.85-0.92, suggesting that the antiaggregatory activity of prasugrel largely reflected P2Y12 blockade achieved in vivo. We further examined the effects of the in vivo P2Y12 inhibition by prasugrel (1-10 mg/kg, po) on MI induced by thrombotic coronary artery occlusion in rats. In surviving rats, infarct size at 24 hours after photoirradiation was evaluated. In the vehicle group, necrosis area/total left ventricular area was 37.9% ± 6.8% (mean ± SE, n = 7). At all prasugrel doses tested (n = 7 for each dose), necrosis area/total left ventricular area was significantly smaller than that in the vehicle group: 14.4% ± 4.0% for 1 mg/kg (P < 0.01), 19.8% ± 4.5% for 3 mg/kg (P < 0.05), and 14.8% ± 3.6% for 10 mg/kg (P < 0.01). At the highest administered dose of prasugrel (10 mg/kg), blood pressure and heart rate were unchanged. Arrhythmia was observed in 5 of 7 animals in the vehicle group at 24 hours after irradiation; in contrast, no arrhythmia was found in the group treated with prasugrel (10 mg/kg). Taken together, these results demonstrate that prasugrel is a selective P2Y12 inhibitor in vivo, providing effective inhibition of platelet aggregation and MI in rats.