Corresponding Author
Key Words: acute myocardial infarction, creatinine kinase-MB, percutaneous coronary intervention, prognosis
Despite significant recent advances, management of acute myocardial infarction (AMI) has always remained a challenging area. Although the restoration of TIMI flow grade 3 through primary percutaneous coronary intervention (PCI) is a cornerstone of AMI treatment, it does not invariably translate into favorable outcomes. A substantial number of patients achieving TIMI flow grade 3 can have persistent ST-segment elevation post-PCI or adverse cardiovascular outcomes which is attributed to microvascular obstruction resulting in inadequate myocardial reperfusion (MR). Cardiac mortality and heart failure in AMI are significantly related to the success of MR. Clearly, methods that can assess MR would be better suited to predict cardiovascular outcomes than TIMI flow grade 3.
Techniques like myocardial blush grade (MBG) have demonstrated a correlation with MR. MBG 3, indicating normal myocardial blush, reflects preserved coronary microvasculature and is associated with improved outcomes compared with reduced blush grades (MBG 0, 1, or 2).1 However, significant intraobserver and interobserver variability limits the reliability and routine application of MBG in clinical practice.
Advanced methods including magnetic resonance imaging, positron emission tomography, or the indexes of microcirculatory resistance have been found to be useful for assessment of MR. Unfortunately, their application in routine clinical settings is constrained by limited availability, procedural complexities, and high costs.2 This calls for simpler and more objective methods to assess MR.
In this issue of JACC: Asia, Shibahashi et al3 propose the time between balloon inflation and peak CK-MB levels (BP time) as an innovative method to assess MR. Serial CK-MB measurements were taken every 3 hours post–primary PCI in patients with TIMI flow grade 3. BP time was categorized into long (>553 minutes) and short (≤553 minutes) durations.
Notably, 19.6% of patients exhibited a long BP time and demonstrated significantly higher 1-year cardiovascular mortality compared with the short BP-time group. The authors hypothesize that an earlier peak in CK-MB levels reflects efficient microvascular washout, indicative of preserved microvascular function.
It is imperative to reduce total ischemia time, which refers to the period between the onset of symptoms and the restoration of blood flow in AMI. The current study explored various time intervals, including onset-to-balloon time, door-to-balloon time, and BP time, to assess their effects on mortality. Although prolonged BP time was associated with increased cardiovascular mortality over 1 year, Door-to-balloon time had no significant impact. Although door-to-balloon time is critical for outcomes in AMI, it has potential limitations. A shorter door-to-balloon time does not always guarantee better myocardial flow or improved outcomes, as these depend on the complex interplay of various clinical and periprocedural factors. BP time emerges as a novel prognostic marker and may play a significant role in predicting long-term outcomes in the postreperfusion period.
Earlier studies have shown that post-PCI higher peak CK levels are associated with increased mortality.4,5 Although this is understandable, high peak levels, when evaluated in the context of time (BP time), do not seem to affect mortality. In the current study, short BP time had higher peak CK-MB levels and yet lower mortality. On the contrary, the long BP-time group had high morality (HR: 2.63 [95% CI: 1.19-5.78]) after adjustment for peak CK-MB values. Lower mortality with higher peak CK-MB levels sounds paradoxical. It might be possible that a gradual washout through the dysfunctional microvasculature over a long period is responsible for the lower peak values in the long BP-time group. This warrants the need for further studies to study the effect CK-MB kinetics as well as peak values on cardiovascular outcomes.
Prior studies have considered both TIMI flow grade 2 and 3 as markers of epicardial coronary patency.5,6 Inclusion of TIMI flow grade 2 hampers the ability to precisely determine the relationship between epicardial revascularization success and MR. Current study results are very insightful, because authors were able to assess the CK-MB kinetics as markers of myocardial reperfusion in fully restored epicardial coronaries by excluding patients with TIMI flow grade <3. This finding reiterates the fact that achieving TIMI flow grade 3 is not enough. Markers of myocardial flow predict long term outcome more accurately.
In the thrombolytic era, studies have shown that coronary artery patency after thrombolysis can be predicted by time activity curves of serum markers.7,8 Rapid increase in CK-MB closely correlated with coronary patency on angiography. It is interesting to note that analysis of rate of rise of biomarkers within first 90 minutes of initiation of thrombolysis was as accurate as the measurement of time to their peak concentration. This strategy of studying the initial slope of cardiac biomarkers rise might be advantageous, because it is more time saving compared with strategy of measuring CK-MB levels every 3 hours as used in the study by Shibahashi et al.3
A few caveats need to be addressed in future studies. The study population includes both ST-segment elevation myocardial infarction (STEMI) and non-STEMI patients, 2 distinct entities with different clinical characteristics and comorbidities. Although non-STEMI patients are more likely to have multivessel coronary artery disease, STEMI patients experience greater myocardial damage, which can significantly affect CK-MB kinetics. It is crucial to investigate BP time in different AMI populations to broaden its applicability. Although CK-MB is a well-established marker, integrating more sensitive biomarkers like high-sensitivity troponins could enhance the prognostic value. Survivor bias and variations in post-PCI management across various centers may have also possibly influenced the observed findings in the study.
Findings of the study strongly advocate the inclusion of CK-MB kinetics (BP time) as a noninvasive index of tissue perfusion. These findings should also rekindle the interest of the interventional cardiology community in using biomarkers to assess tissue reperfusion, potentially offering greater insight than current imaging techniques such as CMR, positron emission tomography, and myocardial contrast echocardiography.
In conclusion, CK-MB kinetics, particularly BP time, offers a promising avenue for assessing myocardial reperfusion and predicting cardiovascular outcomes. This novel, cost-effective approach has the potential to complement existing markers, bridging the gap between advanced imaging techniques and routine clinical practice. By moving beyond TIMI flow grade 3, we can refine our strategies for STEMI management and improve patient outcomes.
Funding Support and Author Disclosures
The author has reported that he has no relationships relevant to the contents of this paper to disclose.
Footnotes
The author attests they are in compliance with human studies committees and animal welfare regulations of the author’s institution and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
References
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