The prognosis of periprocedural myocardial infarction after percutaneous coronary interventions




Abstract


An increase of biomarkers of myocardial necrosis is observed frequently after percutaneous coronary interventions (PCI) even when the procedure seems angiographically successful and otherwise uncomplicated. The recently updated Universal Definition of Myocardial infarction (MI) arbitrarily defined periprocedural MI (type 4a) by elevation of cardiac troponin (cTn) values > 5 × the upper reference limit (URL) in patients with normal baseline values or a rise of cTn values > 20% if the baseline values are elevated, together with either angina or new ECG changes or angiographic loss of patency of a coronary artery or a side branch or persistent slow or no-flow or embolization, or imaging demonstration of new loss of viable myocardium. Most frequent causes of such event are side-branch closure and/or plaque microembolization. The present review is focused on the prognostic implication of periprocedural necrosis. The risk related to a PCI-induced MI is significantly lower as compared to a spontaneous event where a similar increase of biomarkers is detected. Moreover, although an association between CK-MB elevations and adverse prognosis after PCI has been documented, existing data do not support the statement that an isolated elevation of troponins after PCI is associated with an adverse prognosis after PCI; increased troponin levels before PCI seem far more predictive of future events than a peri-procedural itself. Caution should be paid in the interpretation of clinical trials using type 4a MI as a primary endpoint. Nevertheless, patients with periprocedural myocardial damage should be treated as a higher-risk cohort, carefully monitored and receive an intensified secondary prevention program.



Introduction


Percutaneous coronary intervention (PCI) is accomplished with coronary lumen enlargement by a combination of vessel dilation, plaque fracture and the scaffolding provided by stent deployment. Such procedures — although successful in restoring vessel patency and relieving ischemia — may provoke myocardial injury . Indeed, a periprocedural increase of biomarkers of myocardial necrosis is observed frequently after PCI, from 5% to 40% of cases, even when the procedure seems angiographically successful and otherwise uncomplicated . Prognostic implications of such increases remain a matter of considerable controversy and uncertainty. The aim of this review is to provide a current perspective on this issue.





The detection and definition of periprocedural myocardial infarction


After myocardial revascularization, signs of myocardial injury are extremely frequent: ST-segment and T wave abnormalities occur in about 20% of patients, but without clear prognostic relevance .


The development of sensitive and specific assays of serum biomarkers — mainly the creatine kinase (CK) MB isoform, preferably by mass assays, and either troponin (Tn) I or T — has allowed the detection of small amounts of myocardial necrosis. Tn is a constitutive cytoplasmic protein of the myofibrillar thin filament complex involved in muscular excitation–contraction coupling. Cardiac Tn (cTn) is specific for the myocardium. Both cTn-T and cTn-I are currently preferred markers of myocardial injury and have been extensively proposed for CK-MB replacement in clinical practice . However, the traditional interpretation of cTn appearance in the blood as being synonymous to myonecrosis has been recently challenged, as increasing levels of cTnT have been detected following a pacing-induced stress , or high-endurance exercise, without evidence of scar by cardiac magnetic resonance imaging .


With the aim to more precisely and comprehensively define MI, a joint task force of the European Society of Cardiology (ESC), the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA) and the World Heart Federation (WHF) periodically updates the “Universal Definition of Myocardial Infarction”. MI occurring after PCI was defined as type 4a; in the 2007 version the diagnosis of periprocedural MI was suggested after an increase of any myocardial necrosis markers — either cTn or CK-MB — > 3 times the upper reference limit (URL) . The recently updated version ( Table 1 ) has dismissed CK-MB in favor of cTn, has added a pre-procedural evaluation of cTn and coupled the biomarker increase with a clinico-strumental detection of myocardial “injury”: periprocedural MI (type 4a) has been therefore arbitrarily defined by elevation of cTn > 5 × URL in patients with normal baseline values or a rise of cTn values > 20% if the baseline values are elevated, together with either angina or new ECG changes or angiographic loss of patency of a coronary artery or a side branch or persistent slow or no-flow or embolization, or imaging demonstration of new loss of viable myocardium .



Table 1

Classification of different types of myocardial infarction (modified by Thygesen et al. ).

































Type 1 Spontaneous MI
MI is related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection with resulting intraluminal thrombus in one or more of the coronary arteries leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis.
Type 2 MI secondary to an ischaemic imbalance
Myocardial injury with necrosis where a condition other than CAD contributes to an imbalance between myocardial oxygen supply and/or demand.
Type 3 MI resulting in death when biomarker values are unavailable
Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes or new LBBB, but before blood samples could be obtained, cardiac biomarker could rise, or in rare cases cardiac biomarkers were not collected.
Type 4a MI associated with PCI
Elevation of cTn values > 5 × URL in patients with normal baseline values or a rise of cTn values > 20% if the baseline values are elevated, together with either angina or new ECG changes or angiographic loss of patency of a coronary artery or a side branch or persistent slow or no-flow or embolization, or imaging demonstration of new loss of viable myocardium.
Type 4b MI related to stent thrombosis
Detection by coronary angiography or autopsy in the setting of myocardial ischaemia and with a rise and/or fall of cardiac biomarkers values with at least one value > URL
Type 5 MI related to CABG
Elevation of cardiac biomarker values > 10 × URL in patients with normal baseline cTn values. In addition, either new pathological Q waves or new LBBB, or angiographically documented new graft or new native coronary artery occlusion, or imaging evidence of new loss of viable myocardium.

CABG = coronary artery bypass grafting; CAD = coronary artery disease; cTn = cardiac troponins; ECG = electrocardiogram; LBBB = left bundle branch block; MI = myocardial infarction; PCI = percutaneous coronary interventions; URL = upper reference limit.


While an increase of CK-MB after PCI clearly affects late outcome , the currently widespread attitude to substitute CK-MB with cTn together with a non-critical transfer of thresholds agreed upon for one to another — far more sensitive — biomarker would likely cause an overdiagnosis of MI after PCI, with the associated perception that any irreversible ischemic cardiac muscle injury affects long-term outcome . Conflicting evidence emerges specifically in attempts at documenting that an increase of only cTn after PCI with normal CK-MB findings implies an increased risk of “solid” adverse prognostic outcomes . In two recent meta-analyses increased cTn levels were associated with a higher risk of death, but only using univariable analysis . An increase in cTn after PCI has often been associated with some adverse outcome in observational studies with a limited power, where the hard endpoint has seldom been mortality, more often the combined occurrence of death and MI. In the two largest (> 3000 patients) prospective studies , cTn increase after an otherwise “successful” elective PCI did not affect outcome. Cavallini et al. showed that only CK-MB — not cTnI — was associated with increased mortality at a 2-year follow-up, and confirmed this finding in a further analysis restricted to patients with normal CK-MB and cTnI values at baseline without CK-MB elevation after PCI . De Labriolle et al. failed to find any threshold beyond which TnI increase affects outcome. In a recent post-hoc analysis of the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) , serial CK-MB samples were collected after revascularization procedures and the risk of cardiovascular death was increased more than 2-fold (P < 0.001) in patients experiencing type 4a MI (PCI-related) and more than 10-fold (P = 0.035) in those experiencing type 5 MI (CABG-related). Milani et al. assessed only TnI, without CK-MB, after PCI, and showed that any detectable level was an independent predictor of death and MI at 4.2 years: patients with cTn “microleaks” (detectable as increases, but < the 99th percentile) had a long-term mortality similar to subjects with cTn > the 99th percentile (21.4% and 22.8%, respectively, P = NS), significantly higher than patients with normal findings (17.7%, P < 0.005 vs both). When taking into account CK-MB, results were quite different: a similar 45-month mortality was documented for patients with normal post-PCI TnI and CK-MB (4.8%), and with normal CK-MB but elevated TnI (3.9%, P = NS), and was significantly higher in subjects with both increased TnI and CK-MB (13%, P = 0.032) .


The association between postprocedural myonecrosis and outcomes after an otherwise successful PCI seems to be more strongly related to the preprocedural risk: Hubacek et al. documented that presentation with non-ST elevation (NSTE)-acute coronary syndrome (ACS), no statin use, increased C-reactive protein and increasing stent length are independent predictors of TnT rise following PCI; periprocedural TnT rise was not associated with adverse events at a 2-year follow-up. An increased pre-PCI Tn — commonly found (in about 6%) even among patients with chronic heart disease — has been identified as an independent predictor of death or MI after PCI in a large multicenter registry of stable patients and in a study enrolling > 5000 patients undergoing PCI for either stable disease or NSTE-ACS . Therefore, elevations post PCI may well be the result of release of cTn from the ACS event possibly mixed with PCI complication, and it becomes really intricate to distinguish the etiology of the cTn release at this time. In this view the updated consensus document now judiciously suggests to define a type 4a MI in patients admitted with NSTE-ACS when a postprocedural rise of cTn values > 20% is documented.


Nevertheless, under the current definition criteria, cTn seems to be oversensitive in diagnosing postprocedural MI: in two recent limited series of patients undergoing cardiac magnetic resonance early after PCI, the diagnosis of type 4a MI using a cTnI > 3 × URL cutoff had only a “moderate” agreement (kappa = 0.45) with late gadolinium enhancement , and failed to distinguish procedure-related MI from “minor” injury ( Fig. 1 ) . A redefinition of the threshold periprocedural MI to an increase of cTn > 40 × URL has even been suggested , but this too, conversely, would require validation with long-term outcome data .




Fig. 1


Validation of cardiac troponin and CK-MB-defined periprocedural myocardial infarction by magnetic cardiac resonance (modified by Lim et al. ). Peak CK-MB and cardiac troponin (cTn) showed a strong correlation (r 2 = 0.79, p < 0.001), as represented on a natural logarithmic scale. Dashed red lines represent the different thresholds for diagnosing myocardial infarction (MI) after percutaneous coronary intervention when CK-MB and cTnI values are > 3 times upper reference limit (URL). Patients who had a cardiac magnetic resonance evidence of MI with late gadolinium enhancement are here represented with red dots. A CK-MB-based, not a cTn-based definition of periprocedural MI closely approximates evidence of MI by late gadolinium enhancement.


Moreover, currently available ultra high-sensitivity cTn assays are 10 3 to 10 4 -fold more sensitive than the original first and second generation assays, on which most of the literature on periprocedural MI has been based. Such extremely sensible diagnostic tools provide a timely information, that is extremely useful for the early assessment of spontaneous MI. The indiscriminate use of newer cTn assays with the currently recommended cut-off (> 5 times the URL) will likely reduce the specificity of MI diagnosis — always assuming that the term “MI” does not only imply a minor ischemic myocardial damage but has a clear adverse prognostic relevance.





The detection and definition of periprocedural myocardial infarction


After myocardial revascularization, signs of myocardial injury are extremely frequent: ST-segment and T wave abnormalities occur in about 20% of patients, but without clear prognostic relevance .


The development of sensitive and specific assays of serum biomarkers — mainly the creatine kinase (CK) MB isoform, preferably by mass assays, and either troponin (Tn) I or T — has allowed the detection of small amounts of myocardial necrosis. Tn is a constitutive cytoplasmic protein of the myofibrillar thin filament complex involved in muscular excitation–contraction coupling. Cardiac Tn (cTn) is specific for the myocardium. Both cTn-T and cTn-I are currently preferred markers of myocardial injury and have been extensively proposed for CK-MB replacement in clinical practice . However, the traditional interpretation of cTn appearance in the blood as being synonymous to myonecrosis has been recently challenged, as increasing levels of cTnT have been detected following a pacing-induced stress , or high-endurance exercise, without evidence of scar by cardiac magnetic resonance imaging .


With the aim to more precisely and comprehensively define MI, a joint task force of the European Society of Cardiology (ESC), the American College of Cardiology Foundation (ACCF), the American Heart Association (AHA) and the World Heart Federation (WHF) periodically updates the “Universal Definition of Myocardial Infarction”. MI occurring after PCI was defined as type 4a; in the 2007 version the diagnosis of periprocedural MI was suggested after an increase of any myocardial necrosis markers — either cTn or CK-MB — > 3 times the upper reference limit (URL) . The recently updated version ( Table 1 ) has dismissed CK-MB in favor of cTn, has added a pre-procedural evaluation of cTn and coupled the biomarker increase with a clinico-strumental detection of myocardial “injury”: periprocedural MI (type 4a) has been therefore arbitrarily defined by elevation of cTn > 5 × URL in patients with normal baseline values or a rise of cTn values > 20% if the baseline values are elevated, together with either angina or new ECG changes or angiographic loss of patency of a coronary artery or a side branch or persistent slow or no-flow or embolization, or imaging demonstration of new loss of viable myocardium .



Table 1

Classification of different types of myocardial infarction (modified by Thygesen et al. ).

































Type 1 Spontaneous MI
MI is related to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection with resulting intraluminal thrombus in one or more of the coronary arteries leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis.
Type 2 MI secondary to an ischaemic imbalance
Myocardial injury with necrosis where a condition other than CAD contributes to an imbalance between myocardial oxygen supply and/or demand.
Type 3 MI resulting in death when biomarker values are unavailable
Cardiac death with symptoms suggestive of myocardial ischaemia and presumed new ischaemic ECG changes or new LBBB, but before blood samples could be obtained, cardiac biomarker could rise, or in rare cases cardiac biomarkers were not collected.
Type 4a MI associated with PCI
Elevation of cTn values > 5 × URL in patients with normal baseline values or a rise of cTn values > 20% if the baseline values are elevated, together with either angina or new ECG changes or angiographic loss of patency of a coronary artery or a side branch or persistent slow or no-flow or embolization, or imaging demonstration of new loss of viable myocardium.
Type 4b MI related to stent thrombosis
Detection by coronary angiography or autopsy in the setting of myocardial ischaemia and with a rise and/or fall of cardiac biomarkers values with at least one value > URL
Type 5 MI related to CABG
Elevation of cardiac biomarker values > 10 × URL in patients with normal baseline cTn values. In addition, either new pathological Q waves or new LBBB, or angiographically documented new graft or new native coronary artery occlusion, or imaging evidence of new loss of viable myocardium.

Only gold members can continue reading. Log In or Register to continue

Nov 14, 2017 | Posted by in CARDIOLOGY | Comments Off on The prognosis of periprocedural myocardial infarction after percutaneous coronary interventions
Premium Wordpress Themes by UFO Themes