Journal of the American College of Cardiology Ó 2014 by the American College of Cardiology Foundation Published by Elsevier Inc.
EDITORIAL COMMENT
Put Off Till Tomorrow What You Can Do Today* David Antoniucci, MD Florence, Italy
The failure to restore a normal Thrombolysis In Myocardial Infarction (TIMI) flow after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) despite a patent infarct artery is associated with increased mortality. Recent trials on primary PCI show that w10% of patients have no-reflow or slow-reflow after primary PCI, and all studies show that no-flow or slow-reflow is a strong predictor of mortality (1–3). See page 2088
Embolization and ischemic disruption of the microvessel network and the subsequent no-/slow-reflow may occur spontaneously, during recanalization of the infarct vessel by wiring and balloon angioplasty, or after infarct artery stenting. The deterioration of TIMI grade 3 flow after stenting is a good model of procedural no-/slow-reflow independent of the variables associated with an already disrupted microvessel network at the time of intervention (totally occluded infarct artery, long time from symptom onset to recanalization, lack of collateral flow), shows the detrimental effect of atherothrombotic material embolization, and supports the rationale for all mechanical and pharmacological treatments that may reduce or eliminate the thrombus burden. The Deferred Stent Trial in STEMI is a randomized mechanistic trial that used an original approach to thrombus removal or reduction before infarct artery stenting (4). In this issue of the Journal, the investigators hypothesized that after initial achievement of a normal TIMI flow by wiring, nonaggressive balloon angioplasty, or aspiration, a brief deferral of stenting and simultaneous infusion of glycoprotein IIb/IIIa and low molecular weight heparin could result in a decreased thrombotic burden and risk of no-reflow, assuming that the risk of recurrent ischemia
*Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From the Division of Cardiology, Careggi Hospital, Florence, Italy. Dr. Antoniucci has reported that he has no relationships relevant to the contents of this paper to disclose.
Vol. 63, No. 20, 2014 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2014.01.056
during a temporal window of 4 to 16 h might be low. They compared the strategy of deferred stenting with immediate stenting in 101 patients with AMI at high risk of no-/slow-reflow identified by clinical, electrocardiographic, and angiographic variables that are known to be predictors of no-/slow-reflow. The deferred stenting strategy resulted in a dramatic decrease in no-/slow-reflow rate (5.9% vs. 28.6%, odds ratio: 0.16, 95% confidence interval: 0.03 to 0.63; p ¼ 0.005), and, more importantly, the prevention of the no-/slowreflow according to the mechanistic design of the study was associated with improved myocardial reperfusion and myocardial salvage as shown by all angiographic, electrocardiographic, and magnetic resonance imaging (MRI) parameters. Myocardial salvage, defined as the difference between the initial jeopardized area at risk at baseline and final infarct size revealed at 6 months by MRI was greatly improved in the deferred stenting patient group (14.7% vs. 19.7%; p ¼ 0.027). The quality of this finding is very high considering that most of randomized patients had paired MRI (at 2 days and 6 months), and the MRI follow-up rate was very impressive (98%). Recurrence of AMI due to infarct artery reocclusion in the deferred stent group was very low; only 2 patients had reocclusion of the infarcted artery, and both were treated successfully with bail-out stenting. There was no increase in major bleeding or contrast-induced nephropathy in the deferred stenting group. Thus, despite the small number of patients and events, it is likely that the strategy of deferred stenting is safe. If confirmed by ongoing trials on deferred stenting, glycoprotein IIb/IIIa inhibitors will assume again a central role in primary PCI, not only for the reduction of thrombotic burden, but also for the prevention of new thrombotic occlusion if a deferred stenting strategy is adopted. Prolonged infusion of glycoprotein IIb/IIIa inhibitor is able to prevent no-/slow-reflow in the deferred stenting arm, resulting in increased myocardial salvage compared with the immediate stenting group, and it is notable that nearly all patients of the immediate stenting arm (98.9%) received the same antithrombotic treatment after immediate stenting, avoiding the potential for a confounding effect of prolonged infusion of heparin and glycoprotein IIb/IIIa inhibitor on final infarct size and myocardial salvage. Another strength of the study is the collection of data of screened nonrandomized patients in a parallel registry. The registry included both eligible and noneligible patients (310 patients). Overall, the rate of no-/slow-reflow was 14.5%, and in the subgroup of eligible patients at high risk of no-/slow-reflow similar to the one of the immediate stenting arm of the randomized study (23.4% and 28.6%, respectively). This finding confirms the validity of the criteria used for the identification of the patients at high risk of no-/slow-reflow after immediate infarct artery stenting. Indirectly, the study confirms the inability of manual thrombus aspiration to decrease the risk of embolization
2100
JACC Vol. 63, No. 20, 2014 May 27, 2014:2099–100
Antoniucci Put Off Till Tomorrow: What You Can Do Today
and no-/slow-reflow because the large majority of patients of both arms (>85%) received this treatment. This finding is in several ways expected considering that manual aspiration is ineffective in retrieving macroscopic debris in approximately one-third of patients and that the high profile of the catheters increases the risk of embolization when crossing the target lesion. Moreover, even in cases of macrodebris aspiration, optical coherence tomography (OCT) shows a large residual thrombus burden in the majority of patients (5), and this explains the ineffectiveness of manual aspiration in preventing embolism after immediate stenting in patients at high risk of no-/slow-reflow. Consistent with this finding is the fact that most studies on manual aspiration have not demonstrated a reduction in infarct size, and the largest clinical trial on manual aspiration, the TASTE (Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia) trial, have shown no benefit of manual aspiration on clinical outcome (6). An alternative to manual aspiration is rheolytic thrombectomy (RT). A randomized mechanistic study comparing manual aspiration with RT assessing residual thrombus by OCT showed more effective thrombus removal with RT, and patients randomized to RT after stenting had a very high rate of TIMI flow grade 3 (95%) and blush grade 3 (72%) (5). The same TIMI blush grade 3 rate was achieved in the JETSTENT (AngioJET Thrombectomy and STENTing for Treatment of Acute Myocardial Infarction) trial that compared RT plus direct stenting with direct stenting alone (7). However, also with RT, the removal of thrombus is incomplete in most cases (5), and it is unknown whether the residual more organized and less friable thrombus after RT is associated with a decreased potential for embolization in patients at high risk of no-/slow-reflow. The clinical implications of the DEFER-STEMI trial are relevant considering that, according to the criteria used by the DEFER-STEMI investigators for the definition of a high risk of no-/slow-reflow, at least one-half of patients with AMI could be eligible for a deferred stenting strategy.
Using the short temporal window of 4 to 16 h from the restoration of a normal flow, the logistic constraints of the application of this strategy are not insuperable. However, the increased costs of a second procedure should be balanced by the demonstration of improved clinical outcome by a large clinical randomized trial. Reprint requests and correspondence: Dr. David Antoniucci, Division of Cardiology, Careggi Hospital, Viale Morgagni I-50139, Florence, Italy. E-mail: [email protected].
REFERENCES
1. Brener SJ, Moliterno DJ, Aylward PE, et al. Reperfusion after primary angioplasty for ST-elevation myocardial infarction: predictors of success and relationship to clinical outcomes in the APEX -AMI angiographic study. Eur Heart J 2008;29:1127–35. 2. Brener SJ, Cristea E, Mehran R, Dressler O, Lansky AJ, Stone GW. Relationship between angiographic dynamic and densitometric assessment of myocardial reperfusion and survival in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: the harmonizing outcomes with revascularization and stents in AMI (HORIZONS-AMI) trial. Am Heart J 2011;162:1044–51. 3. Caixeta A, Lansky A, Mehran R, et al. Predictors of suboptimal TIMI flow after primary angioplasty for acute myocardial infarction: results from the HORIZONS-AMI trial. EuroIntervention 2013;9:220–7. 4. Carrick D, Oldroyd KG, McEntegart M, et al. A randomized trial of deferred stenting versus immediate stenting to prevent no- or slowreflow in acute ST-segment elevation myocardial infarction (DEFERSTEMI). J Am Coll Cardiol 2014;63:2088–98. 5. Fröbert O, Lagerqvist B, Olivecrona GK, et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med 2013;369:1587–97. 6. Parodi G, Valenti R, Migliorini A, et al. Comparison of manual thrombus aspiration with rheolytic thrombectomy in acute myocardial infarction. Circ Cardiovasc Interv 2013;6:224–30. 7. Migliorini A, Stabile A, Rodriguez AE, et al. Comparison of AngioJet rheolytic thrombectomy before direct infarct artery stenting with direct stenting alone in patients with acute myocardial infarction: the JETSTENT trial. J Am Coll Cardiol 2010;56:1298–306.
Key Words: myocardial infarction - myocardial salvage primary percutaneous coronary intervention.
-
no-reflow
-
EDITORIAL COMMENT
Put Off Till Tomorrow What You Can Do Today* David Antoniucci, MD Florence, Italy
The failure to restore a normal Thrombolysis In Myocardial Infarction (TIMI) flow after primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) despite a patent infarct artery is associated with increased mortality. Recent trials on primary PCI show that w10% of patients have no-reflow or slow-reflow after primary PCI, and all studies show that no-flow or slow-reflow is a strong predictor of mortality (1–3). See page 2088
Embolization and ischemic disruption of the microvessel network and the subsequent no-/slow-reflow may occur spontaneously, during recanalization of the infarct vessel by wiring and balloon angioplasty, or after infarct artery stenting. The deterioration of TIMI grade 3 flow after stenting is a good model of procedural no-/slow-reflow independent of the variables associated with an already disrupted microvessel network at the time of intervention (totally occluded infarct artery, long time from symptom onset to recanalization, lack of collateral flow), shows the detrimental effect of atherothrombotic material embolization, and supports the rationale for all mechanical and pharmacological treatments that may reduce or eliminate the thrombus burden. The Deferred Stent Trial in STEMI is a randomized mechanistic trial that used an original approach to thrombus removal or reduction before infarct artery stenting (4). In this issue of the Journal, the investigators hypothesized that after initial achievement of a normal TIMI flow by wiring, nonaggressive balloon angioplasty, or aspiration, a brief deferral of stenting and simultaneous infusion of glycoprotein IIb/IIIa and low molecular weight heparin could result in a decreased thrombotic burden and risk of no-reflow, assuming that the risk of recurrent ischemia
*Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology. From the Division of Cardiology, Careggi Hospital, Florence, Italy. Dr. Antoniucci has reported that he has no relationships relevant to the contents of this paper to disclose.
Vol. 63, No. 20, 2014 ISSN 0735-1097/$36.00 http://dx.doi.org/10.1016/j.jacc.2014.01.056
during a temporal window of 4 to 16 h might be low. They compared the strategy of deferred stenting with immediate stenting in 101 patients with AMI at high risk of no-/slow-reflow identified by clinical, electrocardiographic, and angiographic variables that are known to be predictors of no-/slow-reflow. The deferred stenting strategy resulted in a dramatic decrease in no-/slow-reflow rate (5.9% vs. 28.6%, odds ratio: 0.16, 95% confidence interval: 0.03 to 0.63; p ¼ 0.005), and, more importantly, the prevention of the no-/slowreflow according to the mechanistic design of the study was associated with improved myocardial reperfusion and myocardial salvage as shown by all angiographic, electrocardiographic, and magnetic resonance imaging (MRI) parameters. Myocardial salvage, defined as the difference between the initial jeopardized area at risk at baseline and final infarct size revealed at 6 months by MRI was greatly improved in the deferred stenting patient group (14.7% vs. 19.7%; p ¼ 0.027). The quality of this finding is very high considering that most of randomized patients had paired MRI (at 2 days and 6 months), and the MRI follow-up rate was very impressive (98%). Recurrence of AMI due to infarct artery reocclusion in the deferred stent group was very low; only 2 patients had reocclusion of the infarcted artery, and both were treated successfully with bail-out stenting. There was no increase in major bleeding or contrast-induced nephropathy in the deferred stenting group. Thus, despite the small number of patients and events, it is likely that the strategy of deferred stenting is safe. If confirmed by ongoing trials on deferred stenting, glycoprotein IIb/IIIa inhibitors will assume again a central role in primary PCI, not only for the reduction of thrombotic burden, but also for the prevention of new thrombotic occlusion if a deferred stenting strategy is adopted. Prolonged infusion of glycoprotein IIb/IIIa inhibitor is able to prevent no-/slow-reflow in the deferred stenting arm, resulting in increased myocardial salvage compared with the immediate stenting group, and it is notable that nearly all patients of the immediate stenting arm (98.9%) received the same antithrombotic treatment after immediate stenting, avoiding the potential for a confounding effect of prolonged infusion of heparin and glycoprotein IIb/IIIa inhibitor on final infarct size and myocardial salvage. Another strength of the study is the collection of data of screened nonrandomized patients in a parallel registry. The registry included both eligible and noneligible patients (310 patients). Overall, the rate of no-/slow-reflow was 14.5%, and in the subgroup of eligible patients at high risk of no-/slow-reflow similar to the one of the immediate stenting arm of the randomized study (23.4% and 28.6%, respectively). This finding confirms the validity of the criteria used for the identification of the patients at high risk of no-/slow-reflow after immediate infarct artery stenting. Indirectly, the study confirms the inability of manual thrombus aspiration to decrease the risk of embolization
2100
JACC Vol. 63, No. 20, 2014 May 27, 2014:2099–100
Antoniucci Put Off Till Tomorrow: What You Can Do Today
and no-/slow-reflow because the large majority of patients of both arms (>85%) received this treatment. This finding is in several ways expected considering that manual aspiration is ineffective in retrieving macroscopic debris in approximately one-third of patients and that the high profile of the catheters increases the risk of embolization when crossing the target lesion. Moreover, even in cases of macrodebris aspiration, optical coherence tomography (OCT) shows a large residual thrombus burden in the majority of patients (5), and this explains the ineffectiveness of manual aspiration in preventing embolism after immediate stenting in patients at high risk of no-/slow-reflow. Consistent with this finding is the fact that most studies on manual aspiration have not demonstrated a reduction in infarct size, and the largest clinical trial on manual aspiration, the TASTE (Thrombus Aspiration in ST-Elevation myocardial infarction in Scandinavia) trial, have shown no benefit of manual aspiration on clinical outcome (6). An alternative to manual aspiration is rheolytic thrombectomy (RT). A randomized mechanistic study comparing manual aspiration with RT assessing residual thrombus by OCT showed more effective thrombus removal with RT, and patients randomized to RT after stenting had a very high rate of TIMI flow grade 3 (95%) and blush grade 3 (72%) (5). The same TIMI blush grade 3 rate was achieved in the JETSTENT (AngioJET Thrombectomy and STENTing for Treatment of Acute Myocardial Infarction) trial that compared RT plus direct stenting with direct stenting alone (7). However, also with RT, the removal of thrombus is incomplete in most cases (5), and it is unknown whether the residual more organized and less friable thrombus after RT is associated with a decreased potential for embolization in patients at high risk of no-/slow-reflow. The clinical implications of the DEFER-STEMI trial are relevant considering that, according to the criteria used by the DEFER-STEMI investigators for the definition of a high risk of no-/slow-reflow, at least one-half of patients with AMI could be eligible for a deferred stenting strategy.
Using the short temporal window of 4 to 16 h from the restoration of a normal flow, the logistic constraints of the application of this strategy are not insuperable. However, the increased costs of a second procedure should be balanced by the demonstration of improved clinical outcome by a large clinical randomized trial. Reprint requests and correspondence: Dr. David Antoniucci, Division of Cardiology, Careggi Hospital, Viale Morgagni I-50139, Florence, Italy. E-mail: [email protected].
REFERENCES
1. Brener SJ, Moliterno DJ, Aylward PE, et al. Reperfusion after primary angioplasty for ST-elevation myocardial infarction: predictors of success and relationship to clinical outcomes in the APEX -AMI angiographic study. Eur Heart J 2008;29:1127–35. 2. Brener SJ, Cristea E, Mehran R, Dressler O, Lansky AJ, Stone GW. Relationship between angiographic dynamic and densitometric assessment of myocardial reperfusion and survival in patients with acute myocardial infarction treated with primary percutaneous coronary intervention: the harmonizing outcomes with revascularization and stents in AMI (HORIZONS-AMI) trial. Am Heart J 2011;162:1044–51. 3. Caixeta A, Lansky A, Mehran R, et al. Predictors of suboptimal TIMI flow after primary angioplasty for acute myocardial infarction: results from the HORIZONS-AMI trial. EuroIntervention 2013;9:220–7. 4. Carrick D, Oldroyd KG, McEntegart M, et al. A randomized trial of deferred stenting versus immediate stenting to prevent no- or slowreflow in acute ST-segment elevation myocardial infarction (DEFERSTEMI). J Am Coll Cardiol 2014;63:2088–98. 5. Fröbert O, Lagerqvist B, Olivecrona GK, et al. Thrombus aspiration during ST-segment elevation myocardial infarction. N Engl J Med 2013;369:1587–97. 6. Parodi G, Valenti R, Migliorini A, et al. Comparison of manual thrombus aspiration with rheolytic thrombectomy in acute myocardial infarction. Circ Cardiovasc Interv 2013;6:224–30. 7. Migliorini A, Stabile A, Rodriguez AE, et al. Comparison of AngioJet rheolytic thrombectomy before direct infarct artery stenting with direct stenting alone in patients with acute myocardial infarction: the JETSTENT trial. J Am Coll Cardiol 2010;56:1298–306.
Key Words: myocardial infarction - myocardial salvage primary percutaneous coronary intervention.
-
no-reflow
-
