Intracoronary imaging in PCI for acute coronary syndrome: Insights from British Cardiovascular Intervention Society registry

Background: While previous studies have demonstrated the superiority of ICI-guided PCI over an angiography-based approach, there are limited data on all-comer ACS patients. This study aimed to identify the characteristics and in-hospital outcomes of patients undergoing intracoronary imaging (ICI) guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Methods: All patient undergoing PCI for ACS in England and Wales between 2006 and 2019 were retrospectively analyzed and strati ﬁ ed according to ICI utilization. The outcomes assessed were in-hospital all-cause mortality and major adverse cardiovascular and cerebrovascular events (MACCE) using multivariable logistic regression models. Results: 598,921 patients underwent PCI for ACS, of which 41,716 (7.0 %) had ICI which was predominantly driven byIVUS use(5.6 %). ICI use steadily increased from 1.4 % in2006to 13.5% in2019. Adjustedodds of mortality(OR0.69,95%CI0.58 – 0.83)andMACCE(OR0.77,95%CI0.73 – 0.83)weresigni ﬁ cantlylowerintheICIgroup. The association betweenICI and improved outcomes variedaccording tovesseltreatedwith both leftmainstem (LMS)andLMS/leftanteriordescending(LAD)PCIassociatedwithsigni ﬁ cantlyloweroddsofmortality(OR0.34, 95%CI 0.27 – 0.44, OR 0.51 95%CI 0.45 – 0.56) and MACCE (OR 0.44 95%CI 0.35 – 0.54, OR 0.67 95%CI 0.62 – 0.72) respectively. Conclusions: Although ICI use has steadily increased, less than one in seven patients underwent ICI-guided PCI. The association between ICI use and improved in-hospital outcomes was mainly observed in PCI procedures involving LMS and LAD. © 2023 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).


Summary
Previous studies have demonstrated superior clinical outcomes with ICI-guided PCI compared to an angiography-based approach; however, there are limited contemporary data on ICI use in an all-comer ACS population.This national analysis demonstrates that the use of ICI in the setting of ACS remains low, despite increasing trends during the study period.The potential benefits of ICI seem to be mainly in LMS/ LAD PCI procedures, with significantly lowers odd of in-hospital mortality and MACCE.

Introduction
Invasive coronary angiography allows the identification and treatment of the culprit lesion in an acute coronary syndrome (ACS) setting.However, many ACS patients do not demonstrate significant obstructive coronary artery disease (CAD) or may have multiple culprit lesions [1,2].In cases of diagnostic uncertainty, intra-coronary imaging (ICI) in the form of either intravascular ultrasound (IVUS) or optical coherence tomography (OCT) plays a pivotal role in the identification of the hallmarks of the culprit lesion, which may subsequently lead to an alternate nonstenting strategy.In those with plaque rupture events or significant coronary disease, ICI provides important additional information over angiography alone with more precise assessment of lesion characteristics, including distribution of calcium, lesion length, reference vessel diameter and stent expansion, thereby improving procedural outcomes [3,4].
Current European Association of Percutaneous Coronary Intervention (EAPCI) expert opinion advocates the adjunctive use of ICI in patients with ACS [5].Previous studies have reported better clinical outcomes for ACS patients undergoing ICI-guided PCI compared to a conventional angiography-based approach [4,[6][7][8][9][10][11].A recent analysis of 13,104 patients with ACS showed that IVUS was associated with significantly lower target lesion failure at 3 years compared to an angiography-based approach [12].However, limited contemporary data exist on the uptake of ICI, temporal trends and associated clinical outcomes in an all-comer national ACS cohort as previous studies have been limited to either an IVUS or OCT approach or focused predominantly on NSTEMI or STEMI only [4,[7][8][9][10]13].Furthermore, there is little data regarding whether any benefit of ICI-guided PCI varies according to the treated vessel.
This study aims to study the temporal growth in the use of ICI, clinical characteristics and angiographic profiles of ACS patients who underwent ICI-guided PCI.We investigated the associations between ICI utilization and clinical outcomes (in-hospital all-cause mortality and MACCE), and the impact of ICI on clinical outcomes in individual coronary vessels.In addition, we aim to assess the individual impact of IVUS and OCT on clinical outcomes compared to angiography-guided PCI.

Methods
We queried the British Cardiovascular Intervention Society (BCIS) PCI registry to include all patients aged>18 years undergoing PCI for ACS between 1st January 2006 to 31st December 2019.The registry collects information from all National Health Service (NHS) acute hospitals about co-morbidities, angiographic findings, procedural pharmacology, and in-hospital outcomes in patients undergoing PCI, constituting over 95 % of all PCI activity in the UK. 14 The encrypted and pseudonymized data are used for audit, research purposes and public reporting without formal individual patient consent under section 251 of NHS act 2006; therefore, the data was processed without individual identifiable information and did not require institutional review board ethical approval [14].
The use of ICI was defined as the use of any imaging modality such as intravascular ultrasound (IVUS), optical coherence tomography (OCT) and optical frequency domain imaging (OFDI).We excluded patients lacking information regarding age, in-hospital death, and ICI use.The final study cohort was then grouped into ICI versus non-ICI groups based on ICI utilization, with further subgroup analysis according to the type of vessel treated using ICI (Supplementary Fig. 1).
The primary outcome was in-hospital mortality, secondary outcomes were major adverse cardiovascular and cerebrovascular events (MACCE; composite of death, acute stroke/transient ischemic attack and reinfarction) and procedural complications as defined in the BCIS registry previously [14].
The patient profiles and procedural characteristics of the ICI group were compared with the non-ICI group.The t-test was used to compare continuous variables, normally distributed and presented as mean values with standard deviations (SD).Categorical variables were reported as numbers and percentages and compared using the Chisquared test.The data were assumed to be missing at random and were accounted for by using multiple imputations with chained equations.The imputation models included linear regression for continuous variables, logistic regression for binary variables and multinomial models for nominal variables.A total of ten imputed datasets were generated before model fitting [15,16].Rubin's rules were used to combine model estimates late [17].Multivariable logistic regression models were performed to assess A) the association between ICI utilization and aforementioned outcomes (in-hospital mortality and MACCE) overall and then stratified according to the type of ICI modality used and type of vessel treated, B) the predictors of receipt of ICI in the overall cohort.Variables adjusted for in the models included: age, sex, ethnicity, clinical syndrome (ST-elevation myocardial infarction (STEMI) or non-STEMI),

Results
A total of 598,921 patients underwent PCI for ACS during the study period, of which 41,716 (7.0 %) had ICI performed.Amongst those undergoing ICI, 36772 (5.6 %) and 8044 (1.4 %) underwent IVUS and OCT, respectively.The percentage of ICI undertaken for an ACS indication steadily increased from 1.4 % in 2006 to 13.5 % in 2019, with a steady increase in the use of both IVUS and OCT (Fig. 1).
Further stratification by EAPCI recommendations for ICI revealed that the uptake of ICI was consistently higher in the NSTEMI group for all indications compared to the STEMI group (Fig. 2).

Discussion
This national report from an all-comer national PCI registry demonstrates that the use of ICI in ACS patients has gradually increased more than ten-fold over the study period.However, even by 2019 less than one in seven patients receive ICI-guided PCI.ICI utilization was predominantly driven by IVUS use, although OCT use was more common in patients presenting with STEMI, previous PCI, and in-stent restenosis.OCT and IVUS use were consistently associated with significantly better clinical outcomes than the non-ICI group.The association between use of ICI and lower odds of in-hospital mortality and MACCE appeared to be only evident in PCI procedures undertaken in LMS/LAD.ICI utilization has previously been reported at <15 % for all comer PCI in the UK [18].In the setting of ACS, we found this was around 7 %, although there was a temporal increase from 1.4 % to 13.5 % during the study period.This is lower than other national reports; a recent Korean study reported IVUS utilization in myocardial infarction at 21.0 %. 12 Similarly, a Japanese report on ICI use in the ACS setting quoted 60 % uptake [19].The results from our study demonstrate low volumes in the context of accumulating evidence for the benefits of ICI [4,12,19,20].Potential explanations for this may be time pressures, lack of operator experience in using and interpreting ICI, and concerns around the risk of downstream embolization of thrombus due to increased instrumentation, particularly in STEMI patients.Although ICI is associated with a high up-front cost, in the UK National Health Service (NHS), operators do not have to seek reimbursement meaning this is less of an issue compared to other countries globally [21].Interestingly, ICI has been shown to be cost-saving in ACS patients and may be more economical than a non-ICI-guided approach at longer term [22].Whilst previous registry data has provided evidence of benefit for ICI in LMS PCI, [23,24] this is the first report to demonstrate that the association between ICI and better outcomes in ACS appears to be mainly in PCI procedures undertaken in the LMS/LAD.The LMS and LAD subtend the largest area of the myocardium, and it is plausible that the most significant prognostic benefit from ICI will come when treating these vessels.Furthermore, ICI aids in identifying areas of high plaque burden requiring specific treatment and assessment of LMS vessel size, which is challenging to assess angiographically due to the lack of a proximal reference vessel [23].
Overall, there was a higher use of IVUS compared to OCT (5.6 % vs 1.3 %), which may be due to the higher rates of IVUS use in patients with LMS PCI, multi-vessel PCI, ostial disease and renal disease.The requirement for blood clearance along with contrast use reduces the applicability of OCT in these patient groups [5].Between 2006 and 2010, there was minimal OCT use likely due to it being a newer ICI method and suggestive of a lag in operators' availability/learning curve.The use of OCT was more prevalent in the setting of STEMI and in-stent restenosis.The strongest predictors of stent thrombosis/restenosis are small luminal areas due to stent under expansion and reference segment disease, including edge dissections and untreated plaque burden [25][26][27].The best modality to identify and treat these issues is ICI, with OCT being the most sensitive technique [5].Nevertheless, both OCT and IVUS were associated with reduced in-hospital mortality and MACCE compared to the non-ICI group across the entire ACS population.
ICI enables accurate lesion sizing and morphological characterization, which improves procedural planning, i.e., correct balloon/stent sizing, calcium modification, and aspiration thrombectomy.It allows for treatment of angiographically unapparent high-risk plaque within and in close proximity to stented segments, thereby reducing the chance of future in-stent restenosis or acute stent thrombosis.Lastly, it allows for the treatment of under-expansion, mal-apposition, significant edge dissections and marked plaque burden at the stent edges which are the main causes of stent failure.Indeed, ICI criteria of suboptimal stent expansion have been shown to be associated with an increased risk of MACCE [28][29][30].
Given the study's observational nature, we could not adjust for variables not collected in the original database.The study does not report on outcome measures such as target vessel repeat revascularization, recurrent MI or MACCE beyond the index hospital admission that would enable us to assess the prognostic benefit of ICI beyond the hospital stay.The BCIS database does not capture the raw IVUS/OCT measurement data, and we could not provide details of the minimal luminal/stent area and correlate these with the outcomes noted in the ICI group.Furthermore, as this information is unavailable, we could not distinguish between upfront imaging use or use later in the procedure.Although there was a clear trend to reduce MACCE with ICI use, the improved outcomes may be confounded by operators' experience and equipment improvement.
This contemporary national report of an all-comer ACS population undergoing PCI shows that less than one in seven patients presenting with ACS undergo ICI-guided PCI despite increasing temporal trends.Although the uptake of ICI was predominantly driven by IVUS use, IVUS and OCT were associated with improved in-hospital mortality and MACCE compared to stand-alone angiography-guided PCI.There was a trend towards greater benefit of ICI-guided PCI in LMS/LAD PCI, which was less evident in PCI to other coronary vessels.

Fig. 1 .
Fig. 1.ICI temporal trends -Temporal trends in the use of ICI between 2006 and 2019 in the overall cohort.

Fig. 2 .
Fig. 2. ICI use in subgroups -Use of ICI as per EAPCI guidelines recommendations in different patient groups EAPCI: European Association of Percutaneous Coronary Intervention, CR: Creatinine, ISR: In-stent restenosis, LMS PCI: Left main stem, PCI: Percutaneous coronary intervention.

Table 2
Baseline characteristics of patients undergoing PCI with no intracoronary imaging (ICI) compared to IVUS or OCT guided PCI.

Table 3
Adjusted odds ratios (OR) and 95 % confidence intervals (CI) of in-hospital outcomes in the intracoronary imaging (ICI) groups (vs.no imaging).

Table 4
Adjusted odds ratios (OR) and 95 % confidence intervals (CI) of in-hospital outcomes in the intracoronary imaging (ICI) groups (vs.no imaging) stratified by vessel.
CI: Confidence Interval, LAD: Left anterior descending, LMS: Left main stem, MACCE: Major adverse cardiovascular and cerebrovascular events.a Any other vessel = left circumflex, right coronary artery, vein graft.