No-reflow Research Articles

A high-volume single center experience of no-reflow post-percutaneous coronary intervention

The no-reflow (NR) phenomenon is frequent in patients with ST-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). However, its real incidence and prognostic significance, so far derived from relatively small patient cohorts, remain poorly defined. We have retrospectively analyzed 19 290 consecutive PCI performed at our hospital between January 1998 and November 2010. NR was defined as a TIMI flow ≤2 at the end of the PCI. In the 1257 patients with STEMI, NR occurred in 9.4% of cases and was more common when the left anterior descending coronary artery was the culprit vessel. STEMI-NR patients had longer ischemic times and more frequently multivessel disease. In the STEMI-NR group, glycoprotein IIb/IIIa inhibitors were used in 60.2%, nitroprusside in 39.6%, thrombus aspiration in 10.7% and adenosine in 8.7%. In the remaining 18033 patients without STEMI undergoing PCI, the NR phenomenon occurred only in 0.2% of cases. STEMI-NR patients had lower left ventricular ejection fraction at discharge (50.3 ± 7.2 vs 44.9 ± 8.4%; p<0.01) and showed higher rates of adverse events (death, non-fatal myocardial infarction, coronary revascularization, new hospital admission for heart failure: 67.8 vs 36.9%, p=0.001), death (25.4 vs 13.2%, p<0.01), myocardial infarction (13.6 vs 4.8%, p<0.01) and hospitalizations for heart failure (13.6 vs 4.8%, p<0.001). Our data, derived from a large cohort of patients from a single center, allow a more correct estimate of the occurrence and prognostic significance of NR. The NR phenomenon is more common in STEMI patients undergoing primary PCI and has an important negative prognostic value.

Vagal nerve stimulation during early reperfusion limits infarct size and no-reflow

Purpose: Infarct Size (IS) and No-Reflow (NR) are important clinical prognosticators of left ventricular (LV) remodeling and dysfunction after acute myocardial infarction (AMI) and both represent important therapeutic targets. Vagal nerve stimulation (VNS) may offer a novel cardioprotective treatment strategy for additional infarct size limitation during reperfusion therapy. VNS was recently shown to limit infarct size in rodents when started prior to, or at the very onset of ischemia. However, its effects on infarct size and no-reflow, have not been investigated in a translational ischemia-reperfusion model. Accordingly, we validated the effects of VNS on infarct size and no-reflow in a porcine model using a translational protocol with treatment starting just prior to reperfusion. Methods: Anesthetized pigs (10 Control, 13 VNS) underwent mid LAD occlusion for 45 min followed by reperfusion. All pigs received a cuff electrode around the left and right cervical vagal trunk but only in VNS pigs, stimulation was started 5 min prior to reperfusion and continued for 20 min. After 120 min of reperfusion, infarct size (% area at risk) and no-reflow (% IS) were assessed using tetrazolium and thioflavin S staining, respectively. Hemodynamics, metabolic and regional function were evaluated as well. Results: VNS decreased heart rate (19±2%, p=0.001) and cardiac output (19±2%, p=0.02) compared with controls, without increasing adverse cardiac events. At the end of the reperfusion period, VNS did not affect systemic hemodynamics, myocardial metabolism or global and regional LV function. The areas at risk were comparable between Control and VNS (26±1% and 27±1% of LV, p=0.60). VNS significantly reduced infarct size compared with controls (67±2% and 54±5% of IS, p=0.03). In addition, VNS was associated with a significant reduction of no-reflow (from 54±6% to 32±6% of IS; p=0.03). No correlation was observed between infarct size or no-reflow reductions and decrease in heart rate (p=0.12 and p=0.19). Conclusions: The present study demonstrates for the first time that the application of VNS during early reperfusion limits infarct size and no-reflow, independent of bradycardia, in a large animal model of ischemia-reperfusion. Thus, VNS may offer a novel, safe and feasible adjunctive therapy of AMI.

Intracoronary fixed dose of nitroprusside via thrombus aspiration catheter for the prevention of the no-reflow phenomenon following primary percutaneous coronary intervention in acute myocardial infarction

Previous studies have shown that intracoronary (IC) nitroprusside (NTP) injection is a safe and effective strategy for the treatment of no-reflow (NR) during percutaneous coronary intervention (PCI). The present study tested the hypothesis that, on the basis of thrombus aspiration for the treatment of ST-segment elevation myocardial infarction (STEMI), the selective IC administration of a fixed dose of NTP (100 μg) plus tirofiban is a safe and superior treatment method compared with the IC administration of tirofiban alone for the prevention of NR during primary PCI. A total of 162 consecutive patients with STEMI, who underwent primary PCI within 12 h of onset, were randomly assigned to two groups: Group A, IC administration of a fixed dose of NTP (100 μg) plus tirofiban (10 μg/kg) and group B, IC administration of tirofiban (10 μg/kg) alone (n=80 and n=82, respectively). The drugs were selectively injected into the infarct-related artery (IRA) via a thrombus aspiration catheter advanced into the IRA. The primary end-point was post-procedural corrected thrombolysis in myocardial infarction (TIMI) frame count (CTFC). The proportion of complete (>70%) ST-segment resolution (STR); the TIMI myocardial perfusion grade (TMPG) 2–3 ratio following PCI; the peak value of creatine kinase (CK)-MB; the TIMI flow grade; the incidence of major adverse cardiac events (MACEs) and the left ventricular ejection fraction (LVEF) after 6 months of follow-up were observed as the secondary end-points. There were no significant differences in the baseline clinical and angiographic characteristics between the two groups. Compared with group B, group A had i) a lower CTFC (23±7 versus 29±11, P=0.000); ii) a higher proportion of complete STR (72.5 versus 55.9%, P=0.040); iii) an enhanced TMPG 2–3 ratio (71.3 versus 53.7%, P=0.030) and iv) a lower peak CK-MB value (170±56 versus 210±48 U/l, P=0.010). There were no statistically significant differences in the final TIMI grade-3 flow between the two groups (92.5 versus 91.5% for groups A and B, respectively; P=0.956). The LVEF at 6 months was higher in group A than group B (63±9 versus 53±11%, respectively; P=0.001); however, the incidence of MACEs was not statistically different between the two groups, although there was a trend indicating improvement in group A (log rank χ2=0.953, P=0.489). The selective IC administration of a fixed dose of NTP (100 μg) plus tirofiban via a thrombus aspiration catheter advanced into the IRA is a safe and superior treatment method compared with tirofiban alone in patients with STEMI undergoing primary PCI. This novel therapeutic strategy improves the myocardial level perfusion, in addition to reducing the infarct size. Furthermore, it may improve the postoperative clinical prognosis following PCI.

Evaluation of clinical and procedural predictors of the no-reflow phenomenon in patients with acute myocardial infarction after primary percutaneous coronary intervention

Objective To find out possible risk factors for no-reflow (NR) phenomenon in patients with acute myocardial infarction (AMI) after primary percutaneous coronary intervention (PCI).Methods A total of 312 consecutive patients with acute myocardial infarction were enrolled from January 2008 to December 2010 at the Cardiology Departmemt of East Hospital,Tongji University School of Medicine in this study.Inclusion criteria were:(1) patients underwent successful primary PCI within 12 h of symptom onset;or (2) patients with ischemic chest pain continuing for more than 12 h underwent successful primary PCI within 24 h of symptom onset.Exculsion criteria were:(1) coronary atery spasm; (2) diameter stenosis of the culprit lesion was ≤50％ and coronary blood flow was normal; (3) patients with severe left main coronary or multivessel disease,who had to require emergency surgical revascularization.According to thrombolysis in myocardial infarction (TIMI) flow grade,the patients were divided into reflow group and NR group.The clinical date,angiography findings and surgical date were compared between two groups.Univariate and multivariate logistic regression were used to determine the predictors for NR phenomenon.Results Sixtyone (20.3％) of the patients developed NR phenomenon after primary PCI.Univariate analysis showed that patients' age,time from onset to reperfusion,systolic blood pressure (SBP) on admission,Killip class of myocardial infarction,intra-aortic balloon pump (IABP) use before primary PCI,TIMI flow grade before primary PCI,type of occlusion,thrombus burden on baseline angiography,target lesion length,reference luminal diameter and method of repusion were correlated with NR phenomenon (P＜ 0.05 for all).Multiple logistic regression analysis identified that age ＞ 65 years (OR =1.470,95％ CI 1.460-1.490,P =0.007),long time from onset to reperfusion ＞6 hours (OR =1.270,95％ CI 1.160-1.400,P =0.001),low SBP on admission ＜100mmHg (1 mmHg=0.133 kPa) (OR=1.910,95％ CI 1.018-3.896,P =0.004),IABP use before PCI (OR =1.949,95％ CI 1.168-3.253,P =0.011),low (≤1) TIMI flow grade before primary PCI (OR =1.100,95％ CI 1.080-1.250,P ＜ 0.01),high thrombus burden (OR =1.600,95％ CI 1.470-2.760,P =0.030) and long target lesion (OR =1.948,95％ CI 1.908-1.990,P =0.019) on angiography as independent predictors of NR phenomenon.ConclusionsThe occurrence of NR phenomenon after primary PCI for acute myocardial infarction can be predicted using simple clinical,angiographic and procedural features. Key words: Acute myocardial infarction ; No-reflow phenomenon; Percutaneous coronary intervention ; Thrombus

Research on No-Reflow Phenomenon after PCI and the Open and Close of Xuanfu

Abstract No-Reflow (NR) is the common complication after percutaneous coronary intervention (PCI). It has a complex pathogenesis. Modern medicine has no ideal prevention and treatment method. Through systematic literature review, in the Xuanfu (mysterious mansion) theory, NR is due to the reason that Qi and blood cannot moisten and nourish myocardium. The key is dysfunction of Xuanfu. Xuanfu is both the gate of Qi ascending, descending, exiting and entering movement and the channel of body fluid circulation. The basic pathogenesis of NR is the blockage of Xuanfu. We propose that the method of dredging Xuanfu can be used in the treatment of NR. It is a new thought for the prevention and treatment of NR. It has a significant meaning for increasing the treatment effect of PCI.

Effect of tissue factor pathway inhibitor-1 on no-reflow phenomenon in rabbit

Objective To observe the effects of different doses of human recombinant tissue factor pathway inhibitor-1 (TFPI-1) on no-reflow (NR) phenomenon in rabbit.Methods Fifty-two New Zealand white rabbits were subjected to coronary artery occlusion for 120 min and followed by reperfusion for 60 min,and then were randomly (random number) assigned into four groups:control group,large,moderate and low doses TFPI-1 groups ( 1000 ng/kg,100 ng/kg,10 ng/kg bolus and thenl0 ng/kg,1 ng/kg and 0.1 ng/kg per minute infusion for maintenance,each group n =13).The no-reflow area (NA) and ischemic area (IA) was measured by thioflavin S and Evan's blue.The NR severity was expressed by NA/IA.The difference in NR severity was compared between groups.The thrombi and myocardial injury were observed under light microscope.The infarction and NR severity in different groups were compared by using one-way ANOVA followed by LSD procedure.Results There were no significant differences in IA and body weight among four groups (P＞0.05).NR severity in the large,moderate,low doses TFPI-1 groups and control group were (0.210 ±0.061 ),(0.389 +0.110),(0.478 ±0.077) and (0.536 ±0.061 ),respectively.NR severity in the large dose TFPI-1 group was slightest among the four groups (P ＜0.01 ).NR severity in the moderate dose TFPI-1 group was significantly decreased than that in control group ( P ＜ 0.01 ) and in low dose TFPI-1 group (P ＜0.05 ).There was no significant difference in NR severity between the low dose TFPI-1 group and control group ( P ＞ 0.05 ).There was less thrombus formation and lower grade myocardial injury found in the large dose TFPI-1 group. Conclusion Human rTFPI-1 might lessen NR severity in rabbit in dose-dependent,suggesting the option on human rTFPI-1 for treatment of NR phenomenon. Key words: No-reflow; Ischemic-reperfusion; Thromboplastin; Tissue factor pathway inhibitor-1( TFPI-1 ); Rabbit

Relationship between Retrograde Coronary Blood Flow and the Extent of No-Reflow and Infarct Size in a Porcine Ischemia–Reperfusion Model

Recanalization of an infarct-related artery does not predictably reflect tissue reperfusion. We examined the relationship between coronary blood flow (CBF) pattern during reperfusion and infarcted (IA) and no-reflow (NR) area in a porcine ischemia-reperfusion model. The mid-left anterior descending artery of 18 pigs was occluded for 1h and reperfused for 2h. CBF during reperfusion was measured with a transit-time ultrasound flowmeter, while systemic arterial and left atrial pressures were monitored. IA and NR were measured with triphenyl tetrazolium chloride and thioflavin staining, respectively. In 13 pigs, early systolic retrograde CBF developed within the first 30min and persisted throughout reperfusion. No retrograde CBF was observed in five pigs. Mean retrograde CBF at 2h of reperfusion predicted a larger IA (r = 0.71; p = 0.001). Time-to-development of retrograde CBF was inversely related to IA (r = -0.55; p = 0.019) and NR (r = -0.62; p = 0.006). A larger IA (OR 1.12, 95% CI 1.01-1.24, p = 0.037) and NR (OR 1.09, 95% CI 1.01-1.18, p = 0.037) predicted the presence of retrograde CBF. Retrograde CBF during recanalization of the infarct-related artery predicts IA and NR and might be used as an index of successful reperfusion at the tissue level.

Cavity volume of ruptured plaque is an independent predictor for angiographic no-reflow phenomenon during primary angioplasty in patients with ST-segment elevation myocardial infarction

Plaque rupture plays a critical role for the development of acute myocardial infarction. However, whether quantitative parameters with regard to the cavity size of ruptured plaque are associated with no-reflow (NR) phenomenon following primary angioplasty remains to be elucidated. A total of 53 patients with de novo ST-elevation myocardial infarction (STEMI) who had plaque rupture at the culprit lesion defined by pre-intervention virtual histology intravascular ultrasound (VH-IVUS) were enrolled. Patients were divided into two groups according to the presence of NR phenomenon: NR group (n=19) and non-NR group (n = 34). By VH-IVUS, we evaluated cavity length, maximum area, and volume of ruptured plaque in culprit lesions. The cavity length, maximum area, and volume were significantly higher in the NR group than those of the non-NR group (4.8 ± 2.1 mm vs. 2.9 ± 4.8 mm, p < 0.001; 3.6 ± 1.4 mm² vs. 1.9 ± 0.5 mm², p < 0.001; 11.5 ± 6.3 mm³ vs. 3.7 ± 2.2 cm³, p < 0.001). A multiple logistic regression analysis revealed that the cavity volume was an independent risk for NR phenomenon. Receiver-operating characteristic analysis revealed that the cavity volume could predict NR phenomenon. The cavity size of ruptured plaque is closely associated with NR phenomenon in patients with STEMI. Evaluation of the cavity volume by VH-IVUS may provide useful information for the prediction of NR phenomenon.

No‐Reflow Phenomenon Following Percutaneous Coronary Intervention for Acute Myocardial Infarction: Incidence, Outcome, and Effect of Pharmacologic Therapy

No-reflow (NR) phenomenon is a well-known problem, often accompanying percutaneous coronary intervention for acute ST elevation myocardial infarction (STEMI). There are little data on effects of pharmacologic therapy on the resolution, outcome, and long-term natural history of NR. Retrospectively assess incidence, management, and prognosis of NR in a tertiary referral hospital. Study included patients with STEMI, treated with percutaneous coronary intervention (PCI). Effect of pharmacologic therapy and long-term outcome were assessed. NR was defined by thrombolysis in myocardial infarction (TIMI) < 3 or myocardial blush grade (MBG) < 3. Of 347 identified subjects, NR occurred in 110 (32%) by TIMI and 198 (57%) by MBG. Higher incidence was identified in men versus women (34% vs. 25% by TIMI, P = 0.08; and 60% vs. 48% by MBG, P = 0.04). Pharmacologic therapy was equally effective in restoring normal flow, increasing TIMI score from 1.62 ± 0.07 to 2.78 ± 0.06 (P < 0.0001) and MBG score from 0.43 ± 0.08 to 2.09 ± 0.11 (P < 0.0001). Twenty-three percent who did not receive pharmacologic therapy developed clinical composite of congestive heart failure, cardiogenic shock, and/or death; only 9% of patients who received pharmacologic therapy developed this composite. Patients with severe NR despite treatment had poorer prognosis. Sixty-five percent of patients who survived and had repeat angiogram about 1.5 years later had spontaneous improvement in coronary flow by MBG. NR is common in STEMI. Treatment with nicardipine, nitroprusside, and verapamil are equally effective in improving flow. If not treated, prognosis is poor.

Microvascular Obstruction and the No-Reflow Phenomenon After Percutaneous Coronary Intervention

C ase presentation A: A 50-year-old diabetic man presented to the hospital after 8 hours of continuous chest pain. Because of acute myocardial infarction of the anterior wall, he underwent direct stenting to an occlusion in the left anterior descending coronary artery. Despite revascularization, suboptimal coronary flow was achieved, and he subsequently developed heart failure. Case presentation B: A 77-year-old man underwent elective stenting of a significant stenosis in a degenerated saphenous vein coronary bypass graft. After the procedure, coronary flow in the graft was severely reduced, and he sustained a myocardial infarction in the subtended myocardial territory. The concept of “no reflow” refers to a state of myocardial tissue hypoperfusion in the presence of a patent epicardial coronary artery. The underlying cause of no reflow is microvascular obstruction, which may be produced by various mechanisms. No reflow can be classified according to the duration of the preceding myocardial ischemia (Figure 1). “Reperfusion no reflow” occurs after primary percutaneous coronary intervention (PCI) for reperfusion of an infarct artery in the setting of acute myocardial infarction (AMI) and may be asymptomatic or may present clinically with continued chest pain and ST-segment elevation. Reperfusion no reflow is preceded by ischemic cell injury, is confined to the irreversibly damaged necrotic zone, and may be exacerbated at the time of reperfusion. Reperfusion no reflow is an independent predictor of adverse clinical outcome after AMI regardless of infarct size and is associated with heart failure and increased mortality.1 Figure 1. Schematic illustrating the effect of duration of preceding myocardial ischemia on mechanism of no reflow (NR). “Interventional no reflow” follows noninfarct PCI and affects myocardium that was not subjected to prolonged ischemia before the procedure. Clinically recognized interventional no reflow that complicates PCI is typically sudden in onset, presenting as acute ischemia with chest …

Comparison of impact of emergency percutaneous revascularization on outcome of patients ≥75 to those

Age is a strong predictor of cardiogenic shock (CS) and death in patients with acute myocardial infarction (AMI). Few data exist on the impact of an early percutaneous coronary intervention (PCI) in older patients in CS complicating AMI. This report assesses the impact of an emergency PCI on 6-month outcomes in patients 75 years of age with AMI complicated by CS due to predominant ventricular failure.  This investigation included consecutive patients with AMI complicated by CS who underwent primary PCI between January 1995 and September 2001. CS due to predominant ventricular failure was defi ned as systolic blood pressure 90 mm Hg (without inotropic or intra-aortic balloon support) that was believed to be secondary to ventricular dysfunction and associated with signs of end-organ hypoperfusion (e.g., cold or diaphoretic extremities, altered mental status, or anuria). The diagnosis of CS was confi rmed during cardiac catheterization by the measurement of a systolic blood pressure 90 mm Hg and left ventricular fi lling pressure 20 mm Hg. Patients in CS with severe mitral regurgitation not due to valve rupture were included. Enrolment criteria for PCI included: (1) chest pain persisting 30 minutes associated with ST-segment elevation of 0.1 mV in 2 contiguous electrocardiographic leads, and (2) admission within 24 hours of symptom onset. Patients were included without any restriction based on age or clinical status on presentation. The only exclusion criterion from the analysis was the previous administration of fi brinolytics. A policy of routine infarct artery stenting was adopted in 1998. Abciximab therapy was strongly encouraged from 1999, and the decision whether to administer abciximab was made after the operator’s assessment of major bleeding risk. Abciximab was administered immediately before the procedure (0.25 mg/kg of body weight followed by a 12-hour infusion at 10 g/min). Patients were routinely treated with aspirin (325 mg/day indefi nitely) and ticlopidine (500 mg/day for 1 month). Creatine kinase measurements were systematically performed during admission, every 3 hours for the subsequent 24 hours, and then every 12 hours for 2 days. The peak value of creatine kinase and the time-to-peak creatine kinase were estimated for each patient. The clinical events considered were death from any cause, reinfarction, and repeat target vessel revascularization within 6 months of the initial revascularization. Patients with 1 event were assigned the highest ranked event according to the previously mentioned list. Coronary fl ow in the infarct-related artery was graded using the Thrombolysis In Myocardial Infarction (TIMI) Study Group classifi cation.1 Collateral fl ow was graded using the classifi cation developed by Rentrop et al.2 No-refl ow phenomenon was defi ned as

Coronary no-reflow is caused by shedding of active tissue factor from dissected atherosclerotic plaque

AbstractDefined angiographically, no-reflow (NR) manifests as an acute reduction in coronary flow in the absence of epicardial vessel obstruction. One candidate protein to cause coronary NR is tissue factor (TF), which is abundant in atherosclerotic plaque and a cofactor for activated plasma coagulation factor VII. Scrapings from atherosclerotic carotid arteries contained TF activity (corresponding to 33.03 ± 13.00 pg/cm2 luminal plaque surface). Active TF was sedimented, indicating that TF was associated with membranes. Coronary blood was drawn from 6 patients undergoing coronary interventions with the distal protection device PercuSurge GuardWire (Traatek, Miami, FL). Fine particulate material that was recovered from coronary blood showed TF activity (corresponding to 91.1 ± 62.16 pg/mL authentic TF). To examine the role of TF in acute coronary NR, blood was drawn via a catheter from coronary vessels in 13 patients during NR and after restoration of flow. Mean TF antigen levels were elevated during NR (194.3 ± 142.8 pg/mL) as compared with levels after flow restoration (73.27 ± 31.90 pg/mL; P = .02). To dissect the effects of particulate material and purified TF on flow, selective intracoronary injection of atherosclerotic material or purified relipidated TF was performed in a porcine model. TF induced NR in the model, thus strengthening the concept that TF is causal, not just a bystander to atherosclerotic plaque material. The data suggest that active TF is released from dissected coronary atherosclerotic plaque and is one of the factors causing the NR phenomenon. Thus, blood-borne TF in the coronary circulation is a major determinant of flow.

Vasoactive Prostaglandins in the Impending No-Reflow State

The impending no-reflow (NRF) state was studied in the rat hindlimb to identify possible biochemical mediators producing the no-reflow phenomenon. After 5 hours of ischemia, the venous effluents draining the ischemic limb and the contralateral nonischemic limb were collected for three 30-minute time periods. Thromboxane B2 (TxB2), prostaglandin E2 (PGE2), and 6-ketoprostaglandin F1 alpha, the stable metabolite of prostacyclin (PGI2), were measured by radioimmunoassay. Venous outflow rate, distal skin perfusion assessed by dermofluorometry, and histology of muscle and skin were examined in control limbs, ischemic limbs, and limbs with impending no reflow. The no-reflow state was characterized by a significantly decreased venous outflow (less than 0.01 ml per minute), decreased skin perfusion (index of fluorescence of 15 percent in no-reflow limbs versus 70 percent in reflow limbs), and absence of thrombosis of the vasculature. The no-reflow state also was associated with 2.4 times more thromboxane B2 and 1.5 times more 6-ketoprostaglandin F1 alpha than that observed in ischemic limbs with reflow. The biosynthesis of vasodilating prostaglandin E2 in the no-reflow state, however, was only 40 percent of the prostaglandin E2 measured in limbs with reflow. We propose that the impending no-reflow state may reflect a state of global microcirculatory "agonal" vasoconstriction, most probably due to an overabundant release of the vasoconstrictor thromboxane relative to the vasodilating prostaglandin E2 and prostacyclin. The likelihood of specific biochemical mechanisms producing the no-reflow state suggests that pharmacologic agents may be able to reverse the impending no-reflow state to improve tissue survival.