Coronary angiography with the use of contrast media is utilized in cardiac catheterization in guiding stent placement. However, the use of coronary angiography in stent implantation in coronary artery disease intervention is limited by several drawbacks, such as the potential of observer bias and interobserver variability. Further technical limitations in angiography exist such as suboptimal visualization of a particular location and angiography only providing information about the contour of the vascular lumen. Angiography does not provide further information regarding the components of the vascular wall being assessed. Angiography is often limited in its ability to detect significant stenosis in the left main coronary artery [1], as there is frequently no reference segment in the left main (LM). It is also limited in ability to analyze the ostial part of the left anterior descending (LAD) and the left circumflex (LCx) because of overlapping anatomy in fluoroscopy, and the planned strategy of percutaneous coronary intervention (PCI) can be significantly altered, for example one or two stents strategy depends on ostial LCx or LAD. Ostial of LM is often not clearly visualized by angiography alone. Because of an unclear reference diameter, accurate sizing of the stent is often challenging. Angiography alone is also limited in its ability to accurately detect stent expansion, which is the most important predictor for in-stent restenosis and in-stent thrombosis [2].

Intravascular ultrasound (IVUS) is an intravascular imaging technique that provides information regarding wall composition on coronary vascular lesions. IVUS allows visualization of the coronary arterial wall using a transducer at the end of the catheter. This transducer emits ultrasound waves which will be reflected by the surroundings and generate detailed information regarding the tunica intima, media, and adventitia of the vessel [3, 4]. Traditionally the usage of coronary angiography only provided information on stenotic vs non-stenotic segments in the coronary arteries. IVUS allows further details to be visualized such as types of plaque, dissections, and calcium depositions [5]. IVUS has also demonstrated that the normal areas on angiography are often markedly abnormal, thus redefining the known extent of atherosclerosis in patients with Coronary Artery Disease (CAD) [5]. Meanwhile, the ability of the angiography to assess the extent of atherosclerotic disease is limited because atherosclerosis has a diffuse nature, intricate shapes within the lumen, and can enlarge coronary vessels [6]. IVUS can provide information for appropriate intervention strategies, for example heavily calcified plaque requiring plaque modification prior to stenting or strategy based on ostial lesions found in side-branches and LM. Additionally, IVUS can accurately detect complications such as geographical miss, stent underexpansion, edge dissection, stent protrusion into the aorta, stent deformation after final kissing balloon dilation, and tissue protrusion into the stent. The advantage of IVUS in cardiovascular outcomes is achieved by the ability to detect abnormalities that were not obvious by angiography. The common angiography procedure has limited ability to detect early atherogenesis in the coronary system. In this meta-analysis we analyzed studies that employed IVUS as a guidance in stent placement in percutaneous coronary interventions. Patients with left main coronary artery disease (LMCAD) tend to have a worse prognosis due to the large ischemic area, thus effective stent placement would benefit this patient group greatly.

It is not surprising that several trials have already proved the superiority of IVUS-guided left main PCI over angiography alone guidance. However, despite these results, the penetration of IVUS guidance of LM PCI is still low. Our meta-analysis aims to evaluate and summarize the current evidence on whether IVUS-guided drug-eluting stent (DES) placement resulted in a better outcome than the angiography-guided DES placement in patients with LMCA disease.

This meta-analysis adheres to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline.

This meta-analysis showed that IVUS-guided DES placement had lower cardiovascular mortality, all-cause mortality, target lesion revascularization, myocardial infarction, and stent thrombosis than angiography alone guided DES placement in both stable and unstable coronary artery disease.

The advantage of IVUS in cardiovascular outcomes is achieved by the ability to detect abnormalities that were not identified or occultly identified by angiography. The common angiography procedure has limited ability to detect early atherogenesis in the coronary system. Coronary angiography also does not offer means to quantify plaque burden or compensatory arterial remodeling [20]. Detection of angiographically occult CAD has significant prognostic value. The results of this meta-analysis are similar to a previous PROSPECT study (Providing Regional Observations to Study Predictors of Events in Coronary Tree), that found major adverse cardiac events after a median follow-up of 3.4 years in patients with lesions deemed non-culprit by initial angiography. These lesions were responsible for future cardiovascular events showed mild abnormalities on angiography at baseline [21].

IVUS offers details regarding the size and structure of the affected vessel, composition and morphology of plaque, and extent of disease. These IVUS-derived parameters are relevant in coronary stenting which will include measurement of stent size, identification of stent morphological change including enlargement and apposition, and avoidance of misplacement at the target location [22].

The capability of IVUS in detecting occult angiographical disease was also observed in patients with stable coronary disease. While the value of PCI in stable coronary disease is highly debated, using IVUS-guided PCI, the Japan Stable Angina Pectoris (JSAP) trial showed a reduction in the incidence of Acute Coronary Syndrome (ACS) in IVUS-guided PCI patients compared to patients receiving medical therapy [23]. On the other hand, this benefit was not seen in the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial in which only conventional angiographically guided PCI was performed [24].

The result of this meta-analysis is similar to the results of the ADAPT-DES study (The Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) which observed a significantly lower rate of myocardial infarction, stent thrombosis, and major adverse cardiovascular event (MACE) in patients with IVUS guided procedures versus angiography alone at 1-year post-PCI follow up, this benefit was particularly seen in ACS patients [25].

In this study, we observed the protective effects of IVUS against future myocardial infarction (HR 0.66 [95% CI 0.48, 0.90], p = 0.008; I${}^2$: 0%, p = 0.98) and stent thrombosis (HR 0.38 [95% CI 0.26, 0.57], p 0.001; I${}^2$: 0%, p = 0.50). This effect seems to be mediated by the ability of IVUS to detect stents under expansion at the time of placement as previously described by a study by Kang et al. [26], in which the author found that patients with under expansion of $>$1 segment had a significantly lower survival rate (2-year MACE free) than patients with no under expansion (90 $\pm$ 3% and 98 $\pm$ 1%, respectively; log-rank p 0.001). Furthermore, IVUS assessed LMCA DES under expansion were a good predictor of MACE using regression analysis (adjusted HR = 5.56; 95% CI, 1.99–15.49; p = 0.001).

Based on the results of this meta-analysis and comparable studies, IVUS shows potential in guiding PCI procedures, patients with IVUS-guided PCI shows lower rates of mortality, stent thrombosis, and myocardial infarction, with these benefits IVUS shows potential in detecting subtle plaques in the left main section of the coronary artery. The expected increase in the cost of procedure/care with the usage of IVUS in LM lesion patients are justified by the potential benefit of using this guidance. PCI guidance using IVUS should be performed by adequately trained professionals to obtain optimal results.

The limitation of this study was the different study designs and follow-up duration of the included studies. 2 RCT and 9 observational studies were analysed for meta-analysis. Studies which was largely different to the rest may responsible for the bias in this meta analysis.

This meta-analysis showed that PCI using IVUS guidance resulted in lower all-cause mortality, cardiovascular mortality, target lesion revascularization, myocardial infarction, and stent thrombosis compared to angiography guidance alone.

The datasets in this meta-analysis are available upon reasonable request.

KK and MRA conceived and designed the study. KK, MRA, MP, and JWM performed extensive search of relevant topics. MRA, MP, and JWM performed review and extensive editing of the manuscript. All authors contributed significantly to the writing of the manuscript. All authors approved the final manuscript. All authors have participated sufficiently in the work and agreed to be accountable for all aspects of the work.

Not applicable.

The authors acknowledge the support from the Dr. Hasan Sadikin General Hospital Bandung for providing the access to many journals for literature searching.

This research received no external funding.

The authors declare no conflict of interest.