Treatment Of No-reflow Phenomenon Research Articles

Intracoronary adenosine compared with adrenaline and verapamil in the treatment of no-reflow phenomenon following primary PCI in STEMI patients

Backgroundno-reflow can complicate up to 25% of pPCI and is associated with significant morbidity and mortality. We aimed to compare the outcomes of intracoronary epinephrine and verapamil with intracoronary adenosine in the treatment of no-reflow after primary percutaneous coronary intervention (pPCI). Methods108 STEMI patients had no-reflow during pPCI were assigned into four groups. Group 1, in which epinephrine and verapamil were injected through a well-cannulated guiding catheter. Group 2, in which same drugs were injected in the distal coronary bed through a microcatheter or perfusion catheter. Group 3, in which adenosine was injected through a guiding catheter. Group 4, in which adenosine was injected in distal coronary bed. Primary end point was the achievement of TIMI III flow and MBG II or III. Secondary end point was major adverse cardiovascular and cerebrovascular events (MACCEs) during hospital stay. ResultsThe study groups did not differ in their baseline characteristics. Primary end point was achieved in 15 (27.8%) patients in the guide-delivery arm compared with 34 (63%) patients in the local-delivery arm, p < 0.01. However, the primary end point did not differ between the epinephrine/verapamil group and the adenosine group (27 (50%) vs 22 (40.7%), p = 0.334). The secondary end points were similar between the study groups. ConclusionLocal delivery of epinephrine, verapamil and adenosine in the distal coronary bed is more effective in achieving TIMI III flow with MBG II or III compared with their guide-delivery in patients who suffered no-reflow during pPCI. There was no difference between epinephrine/verapamil Vs. adenosine.

Distal Intracoronary Delivery of Epinephrine versus Verapamil to Prevent No-Reflow During Primary Percutaneous Coronary Intervention: A Randomized, Open-Label, Trial

Background: Previous trials showed a promising potential use of epinephrine in the treatment of no-reflow phenomenon (the no-reflow phenomenon is multiple pathogenetic processes, which may be attributed to ischemic injuries, distal atherothrombotic embolization, coronary-microcirculation susceptibility to injury, and reperfusion injuries (6)). This study aimed to compare the safety and efficacy of distal intracoronary delivery of epinephrine versus verapamil to prevent no-reflow during primary percutaneous coronary intervention (PPCI). Materials and Methods: We conducted a randomized, open-label, trial on patients undergoing PPCI. Patients were randomized to one of three groups: group I who received distal intracoronary administration of epinephrine; group II who received verapamil; and group III who served as a control group. The primary endpoint in our study was the incidence of no-reflow, defined as a post-procedural (Thrombolysis in Myocardial Infarction) TIMI flow grade (TFG) is &lt; 3 or, in the case of a TFG of 3, when TIMI myocardial perfusion grade (TMPG) is 0 or 1. Results: A total of 120 patients were randomized. The angiographic flow and perfusion parameters were significantly improved in group I and II versus the control group, with better results in epinephrine group only TMPG3 was significantly higher with epinephrine (77.5%) than verapamil (55%) (p = 0.037) and TMPG2 was higher in verapamil (32.5%) than epinephrine (7.5%) (p = 0.003). No reflow is lower with epinephrine than verapamil (25% vs 27.5%); however, with no statistically significant difference (P=0.785). Patients in the three groups has no statistical significant difference in (MACE) or heart failure hospitalization. Conclusion: Epinephrine and verapamil are safe and effective in managing patients with no-reflow during PPCIs. Further studies with a larger sample and a longer duration of follow-up are required to confirm these findings

Efficacy and safety of local intracoronary drug delivery in the distal coronary bed as treatment of no-reflow phenomenon during percutaneous coronary intervention

Abstract Background No-reflow is a complication of percutaneous coronary interventions (PCI), which occurs in 0.6–5% of elective PCIs, but it may be observed in up to 50% of primary PCI cases, involving the treatment of thrombus-containing lesions. An optimal standard treatment of no-reflow (NR) has not yet been established. Intracoronary (IC) vasodilators are being administered for the treatment of NR via the guiding catheter, but sometimes distal flow restoration is not satisfactory especially in patients with TIMI 0 flow. Purpose To investigate the efficacy and safety of local IC drug delivery in the distal coronary bed via a microcatheter as a treatment option of NR phenomenon during PCI. Methods A retrospective analysis of 4606 PCI procedures done in our institution was conducted, to identify patients who suffered from NR during PCI (TIMI 0-I flow in the absence of mechanical obstruction). In patients with NR, local IC infusion of vasodilators (Nitroprusside 50–200 mcg, Adenosine 30–40 mcg) was infused, via a microcatheter or thrombus-aspiration catheter, distal to the angioplasty site. Repeated injections were done with both drugs at the operator's discretion, until best flow was achieved, but without exceeding the maximum recommended dose. If the patient was hypotensive and, thus, the administration of IC vasodilators for treating slow flow/NR was impeded, 100–200 mcg IV phenylephrine were administered, to increase blood pressure. Afterwards, IC vasodilators were infused. Results In 4606 conducted PCIs, 83 patients suffered from NR (1.8%). The age of patients with NR was 65.17±11.69 years. As for the sex, there were 10 female (12.1%) and 73 male (87.9%) patients. The mode of presentation was: 1) STEMI in 28 patients (33.7%), 2) NSTEMI-Unstable Angina in 21 patients (25.3%) and 3) stable angina in 34 patients (41%). NR was observed in 57 patients (68.7%) at post-stenting and in 26 patients (31,3%) at post-dilation. The affected vessel was LAD in 35 patients (42.2%), LCx artery in 16 patients (19.3%), RCA in 28 patients (33.7%) and SVG in 4 patients (4.8%). The IC-infused drug was adenosine in 21 patients and nitroprusside in 62 patients. The total number of infusions was 4.05±1.88. TIMI III flow was achieved in 90.3% of patients and MBG II/III was achieved in 89.1%. The combination of TIMI III flow with MBG II/III was achieved in 87.9% of the patients. In the subgroup of patients with STEMI, the combination of TIMI III flow with MBG II/III was achieved in 85,7% of the patients. As for the complications, a transient systolic pressure drop below 90 mmHg occurred in 4 patients, while there was one death, due to cardiogenic shock complicating acute anterior MI. Conclusion Local IC delivery of vasodilator drugs in the distal coronary bed via microcatheter during PCI is a safe and effective treatment of NR phenomenon, and it can enhance the myocardial perfusion, in addition to reducing infarct's size. Also, it may improve the post-PCI prognosis. Funding Acknowledgement Type of funding sources: None.

Adenosine as an Adjunct Therapy in ST Elevation Myocardial Infarction Patients: Myth or Truth?

Early reperfusion represents the key strategy in ST elevation myocardial infarction. However, reperfusion may induce myocardial damage due to the reperfusion myocardial injury, compromising the full potential of reperfusion therapy and accounting for unfavourable results in high risk patients. Adenosine seems to attenuate ischemia reperfusion injury, and thus represents a promising therapeutic option for treating such patients. However, previous randomized clinical trials have collectively failed to demonstrate whether adenosine can effectively reduce measures of myocardial injury and improve clinical outcome, despite its good basic evidence. The failure of such trials to show a real beneficial action may be in part related to specific factors other than adenosine's clinical efficacy. The purpose of this review is to explain the rationale for the use of adenosine as an adjunctive pharmacological cardio-protective agent following reperfusion of the ischemic myocardium, to address the weakness of previous trials and to summarize the current state of knowledge regarding the effect of adenosine administration on reperfusion myocardial injury in patients with myocardial infarction. Although some preclinical and clinical studies point towards the beneficial role of adenosine in the prevention and treatment of no-reflow phenomenon in myocardial infarction, many unanswered questions still remain, including the optimal clinical indication, mode, dosage, duration and timing of application, and the exact mechanisms leading to potential benefits. Clarifying these issues will depend on further properly designed, adequately powered and well conducted clinical trials, which will probably provide us with the definite answers.

Short-Term Effects of Verapamil and Diltiazem in the Treatment of No Reflow Phenomenon: A Meta-Analysis of Randomized Controlled Trials.

Currently, there is still a lack of an optimal treatment for no reflow phenomenon (NRP). We analyzed the efficacy and safety of using nondihydropyridine calcium channel antagonists (NDHP, verapamil/diltiazem) in patients suffering from NRP. Eight RCTs with 494 participants were eligible for analysis. The pooling analysis showed that intracoronary verapamil/diltiazem injection significantly decreased the occurrence of the coronary NRP (RR: 0.3, 95% CI: 0.16–0.57; P = 0.0002) and reduced corrected thrombolysis in myocardial infarction (TIMI) frame Count (WMD = −9.24, 95% CI −13.91–4.57; P = 0.0001) in patients with NRP. Moreover, verapamil/diltiazem treatment showed superiority in reducing wall motion index (WMI) compared to the control at day 1 (WMD = 0.11, 95% CI: 0.02–0.20; P = 0.02) (P < 0.05). There was also a significantly greater decline at occurrence of the major adverse cardiac events between verapamil/diltiazem and control groups (WMD: 0.4, 95% CI: 0.19–0.84; P = 0.02). However, using verapamil/diltiazem did not provide additional improvement of left ventricular ejection fraction post procedure (at 7 days, WMD, 0.1; 95% CI, −2.43–2.63; P = 0.94; at 30 days, WMD, 0.42; 95% CI, −2.09–2.92; P = 0.75). NDHP use is beneficial in attenuating NRP and reducing 6-month MACEs in patients with NRP.

Prevention and treatment of no-reflow phenomenon by targeting the coronary microcirculation.

The coronary no-reflow phenomenon refers to the post-percutaneous coronary intervention (PCI) state in which, despite successful revascularization of the epicardial conduit coronary arteries, substantial regions of the myocardium do not receive adequate perfusion. In most cases, the underlying mechanism can be attributed to alterations in the microvascular circulation caused by factors intrinsic or extrinsic to the coronary microcirculation. Because the no-reflow phenomenon is associated with poor clinical outcomes, it is of great importantance to identify and apply effective strategies for reducing post-PCI morbidity and mortality. Successful prevention strategies aim to ad dress increased vasoreactivity, intravascular platelet aggregation, microvascular inflammation, and down-stream plaque particle embolization. This review provides an updated overview on the pathomechanism of no-reflow and the current available prevention strategies from the perspective of coronary microcirculation. Although large randomized clinical trials have not yet identified any effective treatment, studying the coronary microcirculation may reveal new therapeutic targets for successful amelioration of the adverse clinical consequences from no-reflow phenomenon.

Role of adenosine as an adjunct therapy in the prevention and treatment of no-reflow phenomenon in acute myocardial infarction with ST segment elevation: review of the current data

Copyright © Polskie Towarzystwo Kardiologiczne INTRODUCTION Numerous clinical studies have indicated the beneficial effects of timely, optimal (without residual stenosis) and sustained patency of an occluded epicardial artery on infarct size reduction, left ventricular (LV) function and clinical outcomes. While these observations validate the experimental findings of time-dependent myocardial salvage, patients with large regions of ischaemia continue to exhibit significant morbidity and mortality. So it is clear that additional strategies are needed to improve outcomes. Emerging evidence suggests that maximising myocardial salvage not only involves restoring the full patency of large epicardial coronary arteries, but also maintains blood flow in microcirculation of the reperfused bed [1]. Experimental models convincingly document the concept of progressive microcirculatory failure (the ‘no-reflow phenomenon’) and no-reflow appears to be an important component of the potential deleterious effect of reperfusion — myocardial reperfusion injury. In animal models, abnormalities of tissue perfusion are associated with an increase of the infarct size, and agents that preserve microvascular flow result in a significant reduction of irreversible myocyte necrosis. Diagnostic techniques to measure tissue perfusion have validated this concept in humans and it is now clear that abnormal tissue perfusion occurs frequently in patients with acute coronary syndromes (ACS) undergoing reperfusion therapy [1–6].

Update in Pharmacological Management of Coronary No-Reflow Phenomenon

The no-reflow phenomenon (NRP) is defined as the lack of adequate myocardial tissue perfusion despite a patent epicardial coronary artery. The incidence of NRP varies between 2-5% of elective percutaneous coronary interventions (PCI) and 30% in primary PCI. Clinically, it is an independent predictor of myocardial infarction, in-hospital mortality, and long-term mortality. It may be categorized in interventional (after PCI, especially in saphenous venous grafts) or reperfusion NRP (after re-opening of a totally occluded coronary artery, usually during primary PCI or thrombolysis). There are many physiopathological factors implicated: distal microembolization, interstitial and intracellular edema, coronary spasm and capillary plugging. Although reperfusion and no reflow is a field of intense research, no single mechanical or pharmacological therapy has demonstrated a clear efficacy against NRP, probably due to its multifactorial nature. Once established, the treatment of NRP is based on vasodilators like adenosine, verapamil, nitroprusside or nicorandil. However, the efficacy of these measures is poor, so every effort should be made to prevent the apparition of NRP. The objective of this report is to provide an update of the pharmacological armamentarium available for the prevention and treatment of NRP, and suggest a systematic approach of the management of NRP according to the different possible clinical scenarios.

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

The Use of Intracoronary Sodium Nitroprusside to Treat No-Reflow after Primary Percutaneous Coronary Intervention in Acute Myocardial Infarction

The no-reflow phenomenon is characterized by an inadequate myocardial tissue perfusion in the presence of a patent epicardial coronary artery. The incidence of no-reflow appears to be highest in patients undergoing primary percutaneous coronary intervention (PCI) in acute myocardial infarction or during PCI of saphenous vein grafts (SVGs). Treatment of no-reflow phenomenon is based on the intracoronary administration of medications that induce vasodilatation in small distal coronary vasculature. Sodium nitroprusside (NTP) is a direct nitric oxide donor and does not require intracellular metabolism to induce vasodilatation in microcirculation. Two patients are reported, in whom no-reflow following primary PCI of SVG and native coronary artery was successfully treated with intracoronary NTP. Repeated injections of 50 microg NTP were given selectively distal to the occlusion site utilizing coronary microcatheter (a total NTP dose of 200 microg was given in both cases). Because of the extremely short half-life, the use of intracoronary NTP was easily tolerated by both patients, without causing prolonged or profound hypotension. The authors therefore propose the use of NTP for treatment of no-reflow phenomenon in both vein grafts and native coronary arteries in the setting of acute myocardial infarction.

1003-95 Thrombus aspiration for the treatment of No-reflow phenomenon complicating primary angioplasty for acute myocardial infarction

1003-95 Thrombus aspiration for the treatment of No-reflow phenomenon complicating primary angioplasty for acute myocardial infarction

Pathophysiology and treatment of no reflow phenomenon in acute myocardial infarction

Pathophysiology and treatment of no reflow phenomenon in acute myocardial infarction

1001-30 Comparison of Different Vasodilators on Coronary Flow Reserve In Patients with Documented Coronary Artery Disease

No-reflow phenomenon after angioplasty or atherectomy may result in important ischemic complications. No-reflow phenomenon is related to distal embolization of microparticulate material and/or spasm in the microcirculation. Maximal vasodilatation of the coronary microcirculation may prevent or terminate episodes of no-reflow phenomenon. In this preliminary study, we evaluated the vasodilatory capacities of agents commonly used during coronary procedures, The coronary flow reserve (CFR = hyperemic/basal flow velocity) was measured with 0.018” Doppler FloWire in coronary arteries with &lt;50% diameter stenoses (6 RCA, 4 LAD, and 10 LCX) in 20 patients (mean age = 64 ± 7 years; 15 men) undergoing angiography (n = 6) or angioplasty (n = 14) in another coronary artery. Random paired CFR measurements in the same artery were obtained with intracoronary adenosine, nitroglycerin (NTG), verapamil, and contrast agents (Hypaque, Hexabrix, and Optiray), with blood injection as a control. After each measurement, basal flow conditions were restored before subsequent test injections. At the doses chosen, there were no hemodynamic or conduction abnormalities, which could influence coronary flow responses. adenosine (6 or 12 μ g) verapamil (100 μ g) verapamil (200 μ g) NTG (50 μ g) NTG (200 μ g) Hypaque (6 ml) Blood (6 ml) CFR * 2.2 ± 0.9 ** 14 ± 0.3 1.5 ± 03 1.7 ± 0.4 1.8 ± 0.5 2.1 ± 0 8 1.2 ± 0 1 Duration * 29 ± 9 *** 58 ± 63 77 ± 57 21 ± 7 22 ± 9 35 ± 10 9 ± 5 * p &lt; 0.001 by ANOVA and multiple pairwise comparisons with Bonferroni correction, using adenosine as the comparison group ** p &lt; 0,001 vs. all others except Hypaque *** p &lt; 0.05 vs. all others except verapamil (100 μ g ) and Hypaque: Duration of hyperemic response in seconds Among different contrast agents, there was no difference in CFR, although duration of hyperemia was significantly longer with Hypaque vs. other contrast agents (p &lt; 0.001 by ANOVA). We conclude that adenosine and Hypaque had the highest vasodilatory effect among the agents tested. These agents should be further studied for a potential benefit in the prevention or treatment of no-reflow phenomenon during angioplasty and atherectomy procedures.