Periprocedural Myocardial Infarction and Embolism-Protection Devices

The Third Universal Definition of Myocardial Infarction: Definition of Periprocedural Myocardial Infarction

The 2012 Third Universal Definition document proposed the following updated definition for PMI: an MI associated with PCI is arbitrarily defined by elevation of troponin values greater than five times the 99th percentile (upper reference limit [URL]) in patients with normal baseline values (≤99th percentile URL) or a rise of troponin values greater than 20% if the baseline values are elevated and are stable or falling. The required enzymatic criteria should be associated with (1) symptoms consistent with myocardial ischemia; (2) new ischemic ECG changes or new left bundle branch block (LBBB); (3) angiographic loss of patency of a major coronary artery or a side branch, a persistent slow- or no-flow state, or embolization; or (4) imaging demonstration of new loss of viable myocardium or new regional wall motion abnormality. PCI-related MI (type 4) is distinguished from spontaneous MI (type 1), secondary MI (type 2), and MI associated with sudden death (type 3) or coronary artery bypass grafting (CABG; type 5). A documented stent thrombosis is recognized as a type 4b MI, whereas an MI associated with restenosis greater than 50% is type 4c ( Table 30.1 ).

When a troponin value is elevated but less than or equal to five times the 99th percentile URL after PCI, and the troponin value was normal before the PCI, or when the troponin value is more than the 99th percentile URL in the absence of ischemic, angiographic, or imaging findings, the task force suggested that the term myocardial injury should be used.

Notably, the universal definition states that troponin is the preferred biomarker, the prognostic significance of which is less well validated than CK-MB in the setting of post-PCI myonecrosis. A large body of literature has demonstrated that post-PCI CK and CK-MB elevations have serious adverse prognostic implications, even in absence of pathologic Q-waves. Three meta-analyses to examine the prognostic impact of periprocedural elevated CK-MB have confirmed a proportionate increase in early and late mortality with rising values. The use of abnormal troponin assays to diagnose type 4a MI is supported by some datasets, although supporting evidence is not as wide ranging as has been demonstrated on the basis of abnormal CK-MB. Troponin is a particularly sensitive biomarker used ubiquitously for risk stratification in patients with ACS, but its widespread adoption has by itself increased the incidence of spontaneous MI and PMIs by 40% to 50%. In contrast to its predictive value in type 1 MI (ACS), existing data on peri- or post-PCI troponin elevation do not establish a clear association with an adverse prognosis. To make the definition more clinically relevant, the biomarker threshold for PMI was raised from greater than three times the 99th percentile URL in the earlier version of the Universal Definition document to greater than five times the 99th percentile URL in the most recent one. Nonetheless, the more recently recommended threshold remains arbitrary, and critics argue that any diagnosis of PMI should be associated with meaningful, well-defined prognostic significance.

The Society of Cardiac Angiography and Interventions Expert Consensus Proposed Definition of Periprocedural Myocardial Infarction

To address the limitations of the universal definition of PMI discussed above, an expert consensus group from the SCAI proposed an alternate definition of clinically relevant MI after PCI, defined as “an event associated with a worsened prognosis.” To this end, the document recommended that CK-MB be the preferred biomarker to assess clinically relevant PMI, defined as a CK-MB 10 or more times the ULN. A lower threshold (≥5 × ULN) may be accepted in the patient in whom new pathologic Q-waves in two or more contiguous leads (or new, persistent LBBB) develop after PCI, although further study is required to validate this threshold. If CK-MB assays are not available, the consensus document suggests a troponin level of 70 or more times the ULN to diagnose a type 4a MI. The authors selected this high troponin threshold so that the prognostic implication would be comparable to that associated with a CK-MB elevation of 10 or more times the ULN.

The following recommendations were made to diagnose post-PCI MI in ACS patients in whom the baseline level has not returned to normal: (1) in patients with elevated troponin (or CK-MB) in whom the biomarker levels are stable or falling, a new CK-MB elevation by an absolute increment of 10 or more times the ULN (or ≥70 × ULN for troponin) from the previous nadir level should be evident; (2) in patients with elevated troponin (or CK-MB) in whom the biomarker levels have not been shown to be stable or falling, there should be a further rise in CK-MB or troponin beyond the most recently measured value by an absolute increment of 10 or more times the ULN in CK-MB or 70 or more times the ULN in troponin plus new ST-segment elevation or depression plus signs consistent with a clinically relevant MI, such as new-onset or worsening heart failure or sustained hypotension.

Enzyme Elevation and Imaging Evidence of Myonecrosis

Although substantial debate surrounds the clinical significance of minor biomarker elevation after PCI, there is solid imaging evidence that biomarker release following PCI corresponds to irreversible myocardial injury, both qualitatively and quantitatively.

One study had 48 patients undergo cardiac magnetic resonance imaging (CMRI) before and after PCI to detect newly developed late gadolinium enhancement (LGE) as evidence of procedure-related myonecrosis. Findings were correlated with serum troponin levels recorded 24 hours after the index PCI. Troponin elevation above the ULN was noted in 37% (14 patients), all with evidence of LGE in the target vessel territory. A linear correlation was also apparent between the troponin level at 24 hours after PCI and the mass (in grams) of newly hyper-enhanced myocardium, both on the early post-PCI scan and on delayed 8-month scans, thus confirming the correlation between periprocedural biomarker release and irreversible myocardial damage ( Fig. 30.1 ).

In addition to confirming the irreversible nature of the myocardial injury, the location of MR hyperenhancement in relation to the PCI target segment may give insight into the pathophysiologic mechanism underlying PMI. When the hyperenhancement is visualized in proximity of the treated segment, side-branch occlusion (SBO) is the more likely explanation. However, in cases in which the myocardial injury/damage is downstream from the treated segment, PMI can be best explained by distal microembolization and adverse platelet and inflammatory reactions in the microcirculation.

Distal Embolization and Periprocedural Myocardial Infarction

Although distal embolization associated with endothelial injury has been recognized for years, the importance of this phenomenon in relation to PCI was not fully appreciated until the last decade. Significant distal embolization can cause no-reflow phenomenon after PCI in large part as a result of microvascular dysfunction, because evidence of myocardial ischemia and reduced antegrade coronary flow are present in the absence of an occlusive epicardial stenosis or side-branch compromise. In a report of patients undergoing PCI for non-STEMI (NSTEMI), those with a postprocedural troponin I elevation were significantly more likely to have reduced tissue-level perfusion than those without a troponin I elevation. Platelet aggregates have been identified in the distal microcirculation and in atherosclerotic debris retrieved from arteries downstream from the site of angioplasty using filter devices ( Fig. 30.2 ).

Clinically, intravascular ultrasound (IVUS) studies provided further insight into the relationship between embolization of plaque material and PMI. Prati and coworkers examined the relationship between change in plaque volume before and after stenting and the degree of CK-MB release in 54 patients. In patients with unstable angina, the reduction in plaque volume was more significant; more importantly, however, such reduction significantly correlated with CK-MB release even after adjusting for other variables that influence PMI. A more recent and sophisticated analysis of 62 patients undergoing complex PCI by Porto and colleagues demonstrated a significant association between the change in target lesion plaque area by IVUS and the mass of myonecrosis assessed by hyperenhancement on MR imaging after PCI. The authors also correlated impaired microvascular flow (thrombolysis in myocardial infarction [TIMI] perfusion grade 0 or 1) with MR evidence of hyperenhancement downstream from the treated segment, hence suggesting that particulate matter from the atherosclerotic plaque disrupted by angioplasty drifts downstream and leads to microvascular obstruction and myonecrosis. With the higher resolution of frequency domain optical coherence tomography (OCT), correlations were made between the morphologic features of plaque and subsequent risk of PMI. In a study of 50 patients undergoing single vessel stenting and OCT imaging before and after PCI, a thin-cap fibroatheroma (TCFA) pre-PCI was defined as a lipid-rich plaque (two or more quadrants of lipid core) with a fibrous cap ≤65 μm. TCFA was more frequently seen in those who developed type 4a MI (76% vs. 41%, P = .017). The association was statistically significant and independent of other variables that predicted the development of type 4a MI.

Platelet Activation

Platelet activation plays a critical role in the development and perpetuation of coronary microvascular obstruction following PCI. By definition, the interventional devices used to treat an epicardial stenosis will result in a break in the endothelial surface and a release of debris into the coronary bloodstream. The exposed intraplaque contents stimulate platelet activation and aggregation at the site of the PCI and probably also in the downstream microvasculature. Thus, the platelet aggregates that plug the microcirculation not only cause mechanical obstruction but also lead to detrimental biochemical responses due to their interaction with the injured endothelium, the neutrophils, and more platelets. The release of vasoactive substances such as serotonin and endothelin-1 from the activated platelets and the injured endothelium lead to intense microvascular vasoconstriction, which accentuates the ischemic injury and resultant myonecrosis. The odds of developing PMI, in a cohort of 151 patients presenting for nonurgent PCI, increased threefold if they were found to be aspirin resistant before the procedure.

Periprocedural ST-Segment–Elevation Myocardial Infarction

A PCI-related infarction presenting with ST-segment elevation is caused by acute and total occlusion of a relatively sizable epicardial coronary branch. This is most commonly the result of abrupt closure of a branch or acute stent thrombosis. On occasion, embolization of large thrombus or atheroma may occlude the distal vessel and cause STEMI; such embolization is more common in degenerated saphenous vein graft (SVG) interventions than in native vessel interventions.