A word of caution*

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Mihaela-Ioana Dregoesc1, Adrian Corneliu Iancu1


1 Department of Cardiology, „Iuliu Hatieganu” University of Medicine and Pharmacy, Cluj-Napoca, Romania
*This editorial reflects the views and opinions of the authors and does not necessarily represent the views and official position of the Romanian Journal of Cardiology.
The editorial board and the publisher disclaim any responsibility or liability for the materials. The authors are liable for the content of the articles.


We read with great interest the review by Moţ et al1 that was published in the latest issue of the Romanian Journal of Cardiology. The review aimed at critically dea-ling with a very hot topic of present-day interventional cardiology: the revascularization strategies in left main atherosclerotic disease. However, we do have some concerns regarding the messages which result from this paper.
A critical review (or overview), as the authors en-title their paper, is a very complex piece of literature that „aims to demonstrate the writer has extensively researched literature and critically evaluated its qua-lity. It goes beyond mere description to include degree of analysis and conceptual innovation and typically re-sults in a hypothesis or model”2. The discussed article1 is a brief listing of past trial results that contributed to the recommendations of the 2018 ESC/EACTS Gui-delines on Myocardial Revascularization3. The above mentioned guidelines have not been quoted in the re-ferences list.
Besides this formal inadequacy, there are other more troublesome issues that have drawn our atten-tion.
To begin with, the overview offers controversial in-formation to its readers. An intravascular ultrasound (IVUS) determined minimal luminal area (MLA) of <6.0 mm2 has long been demonstrated as the optimal cutoff value for left main revascularization, with a sensitivity of 93%4. Most importantly, it has been validated in a large clinical outcome study5. In the 2018 consensus document on left main revascularization, the Euro-pean Bifurcation Club considers the 6.0 mm2 value as the most robust IVUS-derived cutoff for deferring in-tervention6. A cutoff value of 6.0 mm2 also agrees with the theoretical value derived from fractal geometry. Using the currently established 3.0 mm2 as the best MLA cutoff for the left main branches, the left main MLA cutoff by linear law is 5.8mm2, 7,8. The <4.5 mm2 MLA the authors1 presented as proved literature cu-toff was obtained based on the Asian patients’ much smaller anatomy. It is therefore contested and consi-dered inappropriate for the Caucasian population9. Its 75% negative predictive value is suboptimal, as one in four patients with severe ischemia is missed9. In the high-risk clinical scenario of left main disease, this is most certainly unacceptable.
The overview1 also presents a series of cutoff values for the assessment of an optimal stent area in four important anatomical segments: proximal left main, the polygon of confluence, ostial left anterior descen-ding and ostial left circumflex. It must be mentioned however that these results are biased by the lack of a pre-procedural IVUS examination, a limitation the authors themselves admit to10. Moreover, these re-sults are also derived from an Asian population and should therefore be taken very cautiously until further clinical data support their prognostic validity.
We would like to stress out one important as-pect the overview improperly presented. According to its authors1, „clinical outcomes trials are required to recommend imaging as essential part of left main percutaneous coronary interventions”. It must be underlined that the 2018 ESC/EACTS Guidelines on Myocardial Revascularization3 state that IVUS should be considered to optimize treatment of unprotected left main lesions (class IIa indication, level of evidence B)3. In a study including 1670 patients with left main lesions treated with drug eluting stents, IVUS guidance was associated with a reduced rate of major adverse cardiovascular events (MACE) (cardiac death, myocar-dial infarction, or target lesion revascularization) wi-thin three years, as compared to a non-guided strategy (11.3% vs. 16.4%, P=0.04)11. In support of these data, a large recent meta-analysis demonstrated a significantly lower risk of all-cause death, cardiac death and stent thrombosis for IVUS-guided left main interventions11.
There is one important issue the authors failed to address: the role of left main intravascular imaging in the setting of acute coronary syndromes. Besides con-firming the culprit lesion, these examinations defi ne lesion morphology and severity in the not so rare con-text of angiographically ambiguous left main fi ndings12. Most importantly, intravascular imaging can provide additional prognostic information than the classic cli-nical and anatomic risk factors13,14. The IVUS-defined plaque burden is a predictor of subsequent MACE, while the lipid-core burden index as determined by virtual histology IVUS is a predictor of plaque vulnera-bility and is associated with a worse clinical outcome13.
In the end, we would like to highlight some other inadequacies, like the use of unclear expressions (e.g. „a lower quality of DES”, „large non-compliant balloons”). Regarding the fi rst and the third fi gure, ne-ither of them complements the text from a scientific point of view. Both of them are merely „before-and-after” still angiography images of left main percutane-ous revascularization procedures. In the absence of an IVUS evaluation, and of information regarding other clinical and echocardiographic parameters, their direct correlation with the actual long-term patient progno-sis is questionable.
The present letter should be considered as „a word of caution” towards the medical community, as each published paper should be critically read and questio-ned. As Albert Einstein best put it: “Education is not the learning of facts. It is rather the training of the mind to think.”

Conflict of interest: none declared.

References
1. Moţ Ş, Şerban A, Pop D. Percutaneous coronary interventions in left main disease: a critical overview of current recommendations. Ro-manian Journal of Cardiology. 2019;29(3):383-389.
2. Grant MJ, Booth A. A typology of reviews: an analysis of 14 re-view types and associated methodologies. Health Info Libr J. 2009; 26(2):91-108. doi: 10.1111/j.1471-1842.2009.00848.x.
3. Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Bene-detto U, Byrne RA, Collet JP, Falk V, Head SJ, Jüni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sib-bing D, Stefanini GG, Windecker S, Yadav R, Zembala MO; ESC Sci-entific Document Group. 2018 ESC/EACTS Guidelines on myocar-dial revascularization. Eur Heart J. 2019;40(2):87–165.
4. Jasti V, Ivan E, Yalamanchili V, Wongpraparut N, Leesar MA. Corre-lations between fractional fl ow reserve and intravascular ultrasound in patients with an ambiguous left main coronary artery stenosis. Circulation 2004;110:2831–6.
5. de la Torre Hernandez JM, Hernandez Hernandez F, Alfonso F, et al., for the LITRO Study Group. Prospective application of pre-defined intravascular ultrasound criteria for assessment of intermediate left main coronary artery lesions results from the multicenter LITRO study. J Am Coll Cardiol 2011;58:351–8.
6. Burzotta F, Lassen JF, Banning AP3, Lefèvre T, Hildick-Smith D, Chieffo A, Darremont O7, Pan M, Chatzizisis YS, Albiero R, Lou-vard Y, Stankovic G. Percutaneous coronary intervention in left main coronary artery disease: the 13th consensus document from the Eu-ropean Bifurcation Club. EuroIntv. 2018; 14:112-120.
7. Tarakji KG, Brunken R, McCarthy PM, Al Chekakie MO, Abdel Latif A, Pothier CE, Blackstone EH, Lauer MS. Myocardial viability testing and the effect of early intervention in patients with advanced left ventricular systolic dysfunction. Circulation. 2006; 113:230–237.
8. Ramadan R, Boden WE, Kinlay S. Management of Left Main Coro-nary Artery Disease. J Am Heart Asssoc. 2018;7:e008151.
9. de la Torre Hernandez JM, Hernandez Hernandez F, Alfonso F. The Optimal Cutoff Value for Left Main Minimal Lumen Area of 4.5 mm2: A Word of Caution. J Am Coll Cardiol Cardiovasc Interv. 2015;8(1):119-127.
10. Kang S-J, Ahn J-M, Song H, Kim W-J, Lee J-Y, Park D-W, Yun S-C, Lee S-W, Kim Y-H, Lee CW, Mintz GS, Park S-W, Park S-J. Com-prehensive intravascular ultrasound assessment of stent area and its impact on restenosis and adverse cardiac events in 403 patients with unprotected left main disease. Circ Cardiovasc Interv 2011;4:562– 569.
11. de la Torre Hernandez JM, Baz Alonso JA, Go mez Hospital JA, Alfonso Manterola F, Garcia Camarero T, Gimeno de Carlos F, Rou-ra Ferrer G, Sanchez Recalde A, Martinez-Luengas IL, Gomez Lara J, Hernandez . Hernandez F, Perez-Vizcayno MJ, Cequier Fillat A, Per-ez de Prado A, Gonzalez-Trevilla AA, Jimenez Navarro MF, Mauri Ferre J, Fernandez Diaz JA, Pinar Bermudez E, Zueco Gil J. Clinical impact of intravascular ultrasound . guidance in drug-eluting stent implantation for unprotected left main coronary disease: pooled analysis at the patient-level of 4 registries. JACC Cardiovasc Interv. 2014;7:244–254.
12. Ye Y, Yang M, Zhang S, Zeng Y. Percutaneous coronary intervention in left main coronary artery disease with or without intravascular ultrasound: a meta-analysis. PLoS One. 2017;12:e0179756.
13. Johnson TW, Räber L, di Mario C, Bourantas C, Jia H, Mattesini A, Gonzalo N, de la Torre Hernandez JM, Prati F, Koskinas K, Joner M, Radu MD, Erlinge D, Regar E, Kunadian V, Maehara A, Byrne RA, Capodanno D, Akasaka T, Wijns W, Mintz GS, Guagliumi G. Clini-cal use of intracoronary imaging. Part 2: acute coronary syndromes, ambiguous coronary angiography findings, and guiding intervention-al decision-making: an expert consensus document of the Europe-an Association of Percutaneous Cardiovascular Interventions. Eur Heart J. 2019;40(31):2566-2584.
14. Homorodean C, Iancu AC, Leucuţa D, Bălănescu Ş, Dregoesc IM, Spînu M, Ober M, Tãtaru D, Olinic M, Bindea D, Olinic D. New Predictors of Early and Late Outcomes after Primary Percutaneous Coronary Intervention in Patients with ST-Segment Elevation Myo-cardial Infarction and Unprotected Left Main Coronary Artery Cul-prit Lesion. J Interv Cardiol. 2019;8238972.

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