Dr.S.Venkatesan MD

This is an editorial submitted by this author to a leading cardiology journal, which was returned within 24 hours , with a comment that article is unsuitable for publication .Want to know, whether the readers agree with the journal editorial team

The Unfinished Story of “Successful” Primary PCI

Primary percutaneous coronary intervention (pPCI) has revolutionized the management of ST-elevation myocardial infarction (STEMI) and remains the gold standard for restoring coronary perfusion. Angiographic success defined as achieving Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow in the infarct-related artery occurs in more than 90–95% of cases. (1,3)However, this measure reflects epicardial recanalization alone and falls short as an indicator of effective myocardial reperfusion.​.(5)

Cardiac magnetic resonance (MRI/CMR) imaging, myocardial contrast echocardiography, and nuclear perfusion techniques consistently reveal that adequate tissue-level reperfusion occurs in only 60–70% of patients with angiographically successful PPCI. This disparity highlights a critical gap between procedural endpoints and true myocardial salvage.(6)

The Persistent Challenge of Microvascular Obstruction

Despite apparent angiographic success, up to 20–30% of patients exhibit microvascular obstruction (MVO) or “no-reflow.” The pathophysiology of MVO involves distal microembolization, capillary edema, and endothelial dysfunction. (2)

MRI studies have demonstrated MVO in 10–15% of PPCI-treated patients with TIMI 3 flow, often associated with larger infarct size, lower left ventricular (LV) ejection fraction, and worse long-term outcomes. (4,6)

Redefining the Endpoints: From Epicardial Patency to Microvascular Integrity

Left ventricular function remains the most clinically relevant indicator of therapeutic success in STEMI. Persistent LV dysfunction in up to 40% of successfully revascularized patients underscores the inadequacy of angiography based assessment. (3)

TIMI grading system is the universally adopted most popular angiographic flow grading. It has its limitations . It confines with epicardial flow . The max grade is TIMI 3 , and it sort of falsely reassures 

The concept of TIMI 4 flow was originally suggested by Dr Gibson in 1999 , calling hyperemic flow with a low TIMI fame count,  as TIMI 4 flow. For some reason this concept was never adopted, though this term extends the traditional TIMI grading system to include  microcirculatory perfusion.

This proposed category reflects optimal tissue level reperfusion, measurable through myocardial blush grade, the index of microcirculatory resistance (IMR), or perfusion-based MRI parameters. (8,10)TIMI 4, therefore, would define the ultimate therapeutic endpoint in the physiological perfusion at the myocyte level.

Emerging Tools and Strategies for Microvascular Optimization

Several strategies can favorably influence microvascular flow. Intracoronary vasodilators such as adenosine, verapamil, and sodium nitroprusside mitigate microvascular constriction and distal embolization. Deferred stenting techniques may reduce reperfusion injury in selected cases.

Recalibrating the Definition of Successful pPCI

Given the growing evidence base, it is time to reconsider what constitutes “success” in pPCI. A restored epicardial lumen without adequate tissue perfusion represents an incomplete therapeutic achievement.

A Call to Global Cardiovascular Leadership

It is good, if the major professional societies like the American College of Cardiology (ACC), European Society of Cardiology (ESC), and Society for Cardiovascular Angiography and Interventions (SCAI) reassess the criteria used to define procedural success in STEMI interventions. Integrating TIMI 4 flow as a recognized endpoint, along with preservation of maximal left ventricular function, will more accurately define the true success of pPCI.

References

1. Sarkar A, Shravage P. TIMI Grade Flow. https://www.ncbi.nlm.nih.gov/books/NBK482412/ncbi.nlm.nih​
2. Wu KC. CMR of microvascular obstruction and hemorrhage in myocardial infarction. J Cardiovasc Magn Reson. 2012 Nov 22;14:68. ttps://pmc.ncbi.nlm.nih.gov/articles/PMC3514126/pmc.ncbi.nlm.nih​
3. Henriques JP, et al. Predictors of suboptimal TIMI flow after primary angioplasty for acute myocardial infarction: insights from the ATLANTIC trial. EuroIntervention. 2024 Jun 17. https://eurointervention.pcronline.com/article/predictors-of-suboptimal-timi-flow-after-primary-angioplasty-for-acute-myocardialeurointervention.pcronline​
4. Jeyaprakash P, et al. Index of Microcirculatory Resistance to predict microvascular obstruction in STEMI: a meta-analysis. Catheter Cardiovasc Interv. 2024 Feb. https://pubmed.ncbi.nlm.nih.gov/38179600/pubmed.ncbi.nlm.nih​
5. Zeymer U, et al. Impact of TIMI 3 patency before primary percutaneous intervention on outcome in patients with STEMI. EuroIntervention. 2012 Aug;8(8):900-7. https://pmc.ncbi.nlm.nih.gov/articles/PMC3760529/pmc.ncbi.nlm.nih​
6. Eitel I, et al. Clinical Impact of Persistent Microvascular Obstruction in CMR After Reperfused STEMI. JACC Cardiovasc Imaging. 2025. https://pubmed.ncbi.nlm.nih.gov/40357554/pubmed.ncbi.nlm.nih​
7. Pantea-Roșan LR, et al. No-Reflow after PPCI—A Predictor of Short-Term Mortality in STEMI. J Clin Med. 2020 Oct 8;9(10):3145. https://pmc.ncbi.nlm.nih.gov/articles/PMC7563881/pmc.ncbi.nlm.nih​
8. Fearon WF, et al. One-year results from the Assessing MICRO-vascular resistances via IMR to predict outcome in ST-elevation myocardial infarction patients with multivessel disease undergoing primary PCI (AMICRO) trial. Front Cardiovasc Med. 2022 Dec 1;9:1051174. https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.1051174/fullfrontiersin​
9. de Waha S, et al. Prognostic Value of Myocardial Blush Grade in ST-elevation MI. J Am Coll Cardiol. 2022. Available from: https://pmc.ncbi.nlm.nih.gov/articles/PMC9340576/pmc.ncbi.nlm.nih​
10. van ‘t Hof AW, et al. Angiographic assessment of myocardial reperfusion in patients treated with primary angioplasty for acute myocardial infarction: myocardial blush grade. Circulation. 2001 Aug 28;104(9):1130-4. https://pmc.ncbi.nlm.nih.gov/articles/PMC2810032/pmc.ncbi.nlm.nih​

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