Some salient updates relevant to the emergency physicians from the 2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction (STEMI):
The criteria for STEMI
1) ST elevation, of course with, of
≥2 mm (0.2 mV) in men or
≥1.5 mm (0.15 mV) in women for leads V2–V3
and
for other leads, remember as usual,
≥1 mm (0.1 mV) in at least 2 contiguous chest leads or the limb leads
measured at the J point
2) Finally..... finally, new or presumably new LBBB per se is no longer considered a diagnostic criteria for STEMI. To quote the guideline,
In the online data supplement of the guideline (click here to access), the guideline uses the Sgarbossa's criteria as the diagnostic criteria in the presence of LBBB.
Note also that from that section of the online data supplement, ECG diagnosis of STEMI in the setting of RBBB as well as left anterior and posterior fascicular blocks does not require special diagnostic criteria. I've seen people apply incorrectly the Sgarbossa's criteria in the presence of RBBB.
3) Interestingly, posterior wall MI, with ST depression in ≥ 2 precordial leads (V1–V4) as well as
4) STE in "the forgotten lead" (or the "widow maker"), the aVR (with coexistent multi-lead ST depression) has been accorded special places in the diagnostic criteria of STEMI.
5) Not to forget, the hyper-acute T wave in the very early phase of STEMI before the development of STE.
Oxygen supplement in STEMI
The other interesting review from the guideline is that OXYGEN SUPPLEMENT is not for everybody. In fact, the guideline quotes a very interesting Cochrane review results:
Strange. Why would this updated guideline say that oxygen supplement may increase the risk of death when the same ACC/AHA in 2007 assigned Class I recommendation for oxygen use for cases where the SaO2 less than 90% and Class IIa for all patients with UA, NSTEMI or uncomplicated STEMI?
First, let's look at what are the rationale for the recommendation for oxygen use:
In a Cochrane review by Cabello et al (2013), reviewing four randomized controlled trials (n = 430 participants) of patients with suspected or proven AMI (STEMI or NSTEMI) less than 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air and regardless of cotherapies provided, the pooled RR of death was 2.05 (95% CI 0.75 to 5.58) in an intention-to-treat analysis and 2.11 (95% CI 0.78 to 5.68) in participants with confirmed AMI. While suggestive of harm, the small number of deaths recorded means that this could be a chance occurrence.
Reference:
Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD007160. DOI: 10.1002/14651858.CD007160.pub3. URL: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007160.pub3/abstract)
.
According to the guideline, oxygen therapy is appropriate for patients who are hypoxemic SaO2 less than but it may paradoxically cause coronary vasoconstriction and increased coronary vascular resistance.
Why is that so? In an excellent review article by Moradkhan and Sinoway in the Journal of the American College of Cardiology titled "Revisiting the Role of Oxygen Therapy in Cardiac Patients" (click here to access full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941910/#!po=18.7500), the authors listed a few possible mechanisms of hyperoxia coronary vasoconstriction:
1. Hyperoxia leads to the generation of reactive oxygen species
Hyperoxia leads to the generation of reactive oxygen species. This in turn decreases the bioavailability of nitric oxide and results in vasoconstriction.
2. The role of K+ATP channels in hyperoxia induced vasoconstriction
During hypoxia and ischemia, a fall in the intracellular ATP concentrations mediates the opening of ATP-sensitive potassium channels, which in turn causes hyperpolarization of the vascular smooth muscle cells and vasodilation. However, in hyperoxic situations, the closure of these K+ATP channels, mediate coronary vasoconstriction.
3. Hyperoxia can induce vasoconstriction by acting directly on L-type Ca2+ channels
Animal studies demonstrate that oxygen sensitive L-Type calcium channels are present on vascular smooth muscle cells that control the local circulatory flow during hypoxia and hyperoxia.
4. Hyperoxia may affect the release of angiotensin II with subsequent changes in endothelin-1 levels
Isolated cardiac myocyte studies demonstrate that angiotensin I is produced with hyperoxia and is subsequently converted to angiotensin II possibly on the surface of endothelial cells. Angiotensin II promotes endothelin-1 release and thereby causes vasoconstriction.
5. Hyperoxia increases the production of potent vasoconstrictor 20-HETE
Hyperoxia induces the production of 20-HETE, an arachidonic acid metabolite and a potent vasoconstrictor in myogenic regulation.
The newer antiplatelet agents
Two newer P2Y12 inhibitors are discussed besides clopidogrel, viz., prasugrel and ticagrelor (* P2Y12 has been shown to be the chemoreceptor for ADP, thus P2Y12 inhibitors inhibit ADP).
Clopidogrel has been used for a long time but the antiplatelet acivitiy of clopidogrel may vary due to reasons such as different patient phenotypes (obesity, diabetes mellitus) as well as hepatic CYP450 enzyme system polymorphisms that may interfere with clopidogrel biotransformation.
Prasugrel has been shown to achieve a greater antiplatelet aggregation than clopidogrel. In the TRITON-TIMI 38 trial, prasugrel has been shown to result in a lower 30-day rate of the composite primary outcomes of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke as compared to clopidogrel in patients with ACS for whom an invasive strategy was planned. The benefits of prasugrel relative to clopidogrel in STEMI must be weighed against the increase in the risk of bleeding with prasugrel.
Ticagrelor is a reversible, nonthienopyridine P2Y12 inhibitor that does not require metabolic conversion to active drug. Ticagrelor has been gaining quite a bit of publicity due to its landmark study, the PLATO trial. The PLATO trial shows that treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding.
However, a rather interesting finding in a subgroup analysis in the PLATO trial showed a significant interaction between treatment effect and geographic region, with an apparently smaller ticagrelor effect in North America than in other areas. This phenomenon of geographical variation is not exactly known - it could be due to chance alone, or it could be due to higher aspirin doses commonly used in the United States.
Although 1 year of dual antiplatelet therapy (DAPT) is recommended after stent implantation during primary PCI for STEMI, earlier discontinuation of a P2Y12 inhibitor may be necessary if the risk of morbidity from bleeding outweighs the anticipated benefit of DAPT.
Fondaparinux
Fondaparinux has been widely used in our setting. The guideline however, states that Fondaparinux has been associated with catheter thrombosis. Therefore, Fondaparinux should not be given as the sole anticoagulant to patients referred for PCI. Additional intravenous boluses of UFH (or bivalirudin) should be administered. Fondaparinux is also contraindicated for patients with a creatinine clearance less than 30 ml per min.
The criteria for STEMI
1) ST elevation, of course with, of
≥2 mm (0.2 mV) in men or
≥1.5 mm (0.15 mV) in women for leads V2–V3
and
for other leads, remember as usual,
≥1 mm (0.1 mV) in at least 2 contiguous chest leads or the limb leads
measured at the J point
2) Finally..... finally, new or presumably new LBBB per se is no longer considered a diagnostic criteria for STEMI. To quote the guideline,
New or presumably new LBBB at presentation occurs infrequently, may interfere with ST-elevation analysis, and should not be considered diagnostic of acute myocardial infarction (MI) in isolation.
In the online data supplement of the guideline (click here to access), the guideline uses the Sgarbossa's criteria as the diagnostic criteria in the presence of LBBB.
Note also that from that section of the online data supplement, ECG diagnosis of STEMI in the setting of RBBB as well as left anterior and posterior fascicular blocks does not require special diagnostic criteria. I've seen people apply incorrectly the Sgarbossa's criteria in the presence of RBBB.
3) Interestingly, posterior wall MI, with ST depression in ≥ 2 precordial leads (V1–V4) as well as
4) STE in "the forgotten lead" (or the "widow maker"), the aVR (with coexistent multi-lead ST depression) has been accorded special places in the diagnostic criteria of STEMI.
5) Not to forget, the hyper-acute T wave in the very early phase of STEMI before the development of STE.
Oxygen supplement in STEMI
The other interesting review from the guideline is that OXYGEN SUPPLEMENT is not for everybody. In fact, the guideline quotes a very interesting Cochrane review results:
A pooled Cochrane analysis of 3 trials showed a 3-fold higher risk of death for patients with confirmed acute MI treated with oxygen than for patients with acute MI managed on room air. ....Supplementary oxygen may, however, increase coronary vascular resistance.
Strange. Why would this updated guideline say that oxygen supplement may increase the risk of death when the same ACC/AHA in 2007 assigned Class I recommendation for oxygen use for cases where the SaO2 less than 90% and Class IIa for all patients with UA, NSTEMI or uncomplicated STEMI?
First, let's look at what are the rationale for the recommendation for oxygen use:
- increasing arterial oxygen tension decreases the acute ischemic injury and the eventual infarct area and
- the observation that some uncomplicated myocardial infarction patients have arterial hypoxemia due to fluid retention in the lungs and a ventilation-perfusion mismatch
In a Cochrane review by Cabello et al (2013), reviewing four randomized controlled trials (n = 430 participants) of patients with suspected or proven AMI (STEMI or NSTEMI) less than 24 hours after onset, in which the intervention was inhaled oxygen (at normal pressure) compared to air and regardless of cotherapies provided, the pooled RR of death was 2.05 (95% CI 0.75 to 5.58) in an intention-to-treat analysis and 2.11 (95% CI 0.78 to 5.68) in participants with confirmed AMI. While suggestive of harm, the small number of deaths recorded means that this could be a chance occurrence.
Reference:
Cabello JB, Burls A, Emparanza JI, Bayliss S, Quinn T. Oxygen therapy for acute myocardial infarction. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD007160. DOI: 10.1002/14651858.CD007160.pub3. URL: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD007160.pub3/abstract)
.
According to the guideline, oxygen therapy is appropriate for patients who are hypoxemic SaO2 less than but it may paradoxically cause coronary vasoconstriction and increased coronary vascular resistance.
Why is that so? In an excellent review article by Moradkhan and Sinoway in the Journal of the American College of Cardiology titled "Revisiting the Role of Oxygen Therapy in Cardiac Patients" (click here to access full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2941910/#!po=18.7500), the authors listed a few possible mechanisms of hyperoxia coronary vasoconstriction:
1. Hyperoxia leads to the generation of reactive oxygen species
Hyperoxia leads to the generation of reactive oxygen species. This in turn decreases the bioavailability of nitric oxide and results in vasoconstriction.
2. The role of K+ATP channels in hyperoxia induced vasoconstriction
During hypoxia and ischemia, a fall in the intracellular ATP concentrations mediates the opening of ATP-sensitive potassium channels, which in turn causes hyperpolarization of the vascular smooth muscle cells and vasodilation. However, in hyperoxic situations, the closure of these K+ATP channels, mediate coronary vasoconstriction.
3. Hyperoxia can induce vasoconstriction by acting directly on L-type Ca2+ channels
Animal studies demonstrate that oxygen sensitive L-Type calcium channels are present on vascular smooth muscle cells that control the local circulatory flow during hypoxia and hyperoxia.
4. Hyperoxia may affect the release of angiotensin II with subsequent changes in endothelin-1 levels
Isolated cardiac myocyte studies demonstrate that angiotensin I is produced with hyperoxia and is subsequently converted to angiotensin II possibly on the surface of endothelial cells. Angiotensin II promotes endothelin-1 release and thereby causes vasoconstriction.
5. Hyperoxia increases the production of potent vasoconstrictor 20-HETE
Hyperoxia induces the production of 20-HETE, an arachidonic acid metabolite and a potent vasoconstrictor in myogenic regulation.
The newer antiplatelet agents
Two newer P2Y12 inhibitors are discussed besides clopidogrel, viz., prasugrel and ticagrelor (* P2Y12 has been shown to be the chemoreceptor for ADP, thus P2Y12 inhibitors inhibit ADP).
Clopidogrel has been used for a long time but the antiplatelet acivitiy of clopidogrel may vary due to reasons such as different patient phenotypes (obesity, diabetes mellitus) as well as hepatic CYP450 enzyme system polymorphisms that may interfere with clopidogrel biotransformation.
Prasugrel has been shown to achieve a greater antiplatelet aggregation than clopidogrel. In the TRITON-TIMI 38 trial, prasugrel has been shown to result in a lower 30-day rate of the composite primary outcomes of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke as compared to clopidogrel in patients with ACS for whom an invasive strategy was planned. The benefits of prasugrel relative to clopidogrel in STEMI must be weighed against the increase in the risk of bleeding with prasugrel.
Ticagrelor is a reversible, nonthienopyridine P2Y12 inhibitor that does not require metabolic conversion to active drug. Ticagrelor has been gaining quite a bit of publicity due to its landmark study, the PLATO trial. The PLATO trial shows that treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding.
However, a rather interesting finding in a subgroup analysis in the PLATO trial showed a significant interaction between treatment effect and geographic region, with an apparently smaller ticagrelor effect in North America than in other areas. This phenomenon of geographical variation is not exactly known - it could be due to chance alone, or it could be due to higher aspirin doses commonly used in the United States.
Although 1 year of dual antiplatelet therapy (DAPT) is recommended after stent implantation during primary PCI for STEMI, earlier discontinuation of a P2Y12 inhibitor may be necessary if the risk of morbidity from bleeding outweighs the anticipated benefit of DAPT.
Fondaparinux
Fondaparinux has been widely used in our setting. The guideline however, states that Fondaparinux has been associated with catheter thrombosis. Therefore, Fondaparinux should not be given as the sole anticoagulant to patients referred for PCI. Additional intravenous boluses of UFH (or bivalirudin) should be administered. Fondaparinux is also contraindicated for patients with a creatinine clearance less than 30 ml per min.
Greetings Dr Chew,
ReplyDeleteThank you for a very interesting sharing :) it was very informative and updated info. I am interested in the issue regarding supplemental o2 in acs patients that u brought up here. Since it was proven that it may caused coronary vasoconstriction, what are the aha recommendation for selection of patient in whom supplemental o2 is advisable? Thank you :)