Primary Percutaneous Coronary Intervention Guided by High‐Definition Intravascular Ultrasound (The SPECTRUM Study)

ABSTRACT

Background

Limited data are available on the use of intravascular ultrasound (IVUS) in patients presenting with ST‐segment elevation myocardial infarction (STEMI).

Aims

This study aimed to assess the impact of IVUS‐guided primary percutaneous coronary intervention (PCI).

Methods

SPECTRUM (NCT05007535) was a prospective, single‐center, observational cohort study. STEMI patients presenting within 12 h after symptom onset with stable hemodynamics and undergoing primary PCI of a native culprit lesion (angiographic reference diameter ≥ 2.25 mm) were eligible. Pre‐intervention, post‐intervention and post‐optimization (if applicable) HD‐IVUS pullbacks were obtained per protocol. The primary endpoint was target vessel failure (TVF) at 12 months, a composite of cardiovascular death, target vessel myocardial infarction, and target vessel revascularization. The secondary endpoint was presence of IVUS‐guided optimization.

Results

A total of 200 STEMI patients were included. Mean age was 62.1 (±12.5) years, 69% were male, 11.0% had diabetes and the left anterior descending was the culprit vessel in 44.0%. IVUS‐guided optimization was performed in 41.1%. Optimal PCI, based on predefined IVUS criteria, increased from 52.1% post intervention to 65.5% post optimization (p < 0.001). A stent‐edge plaque burden > 50% was the main reason for not achieving optimal PCI results after IVUS‐guided optimization (94.4%). TVF at 12 months occurred in 3.0% (95% CI 1.1%−6.4%).

Conclusions

SPECTRUM is the first dedicated prospective study demonstrating the potential of IVUS to optimize outcomes in a primary PCI setting. IVUS guidance in primary PCI was safe, significantly increased the number of STEMI patients with an optimal PCI result and resulted in low rates of TVF at 12 months.

1. Introduction

In patients with coronary artery disease undergoing percutaneous coronary intervention (PCI), intravascular ultrasound (IVUS) facilitates tailored lesion preparation, accurate stent sizing and optimization guidance, resulting in superior clinical outcome as compared to angiography‐guided PCI [1, 2, 3, 4, 5, 6, 7].

A wealth of data supporting the use of intravascular imaging resulted in a class IA recommendation to use either IVUS or optical coherence tomography in patients with chronic coronary syndrome [8]. However, studies supporting the use of IVUS in a primary PCI setting are limited to a single randomized trial in a more general acute coronary syndrome (ACS) population and a meta‐analysis of observational studies suggesting that the beneficial impact of IVUS‐guided PCI may also be extended to patients with acute myocardial infarction [9, 10, 11, 12].

As primary PCI can be challenged by spasm, (spontaneous) dissection, more complex lesion morphology (e.g. plaque ruptures, calcified nodules and thrombus), stent thrombosis, and no‐reflow, patients presenting with ST‐segment elevation myocardial infarction (STEMI) may derive particular benefit from IVUS‐guided procedures [13, 14, 15, 16]. In addition to its general advantages, recent data demonstrated that high‐definition IVUS (HD‐IVUS, i.e., 40−60 MHz) can be used for culprit lesion plaque characterization and thrombus assessment in these patients [17, 18].

Nevertheless, the impact of IVUS‐guided primary PCI on optimization strategies and clinical outcome remains unclear. “Tissue characterization and primary PCI guidance using IVUS” (SPECTRUM) is the first dedicated prospective study assessing the safety and efficacy of IVUS guidance in patients presenting with STEMI [19].

2. Methods

2.1. Study Design and Patient Population

The design of the study has been described previously [19]. SPECTRUM was a prospective, investigator‐initiated, single‐center, observational cohort study performed at the Erasmus University Medical Center, Rotterdam, the Netherlands (NCT05007535). The study was approved by the local ethics committee on October 7, 2020, and was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice. All patients provided written informed consent.

Adult STEMI patients undergoing primary PCI for a native coronary artery culprit lesion with an angiographic vessel reference diameter ≥ 2.25 mm were eligible. STEMI was defined according to the fourth universal definition of myocardial infarction [20]. Cardiogenic shock (i.e., systolic blood pressure < 90 mmHg or the need for vasopressor or mechanical circulatory support) and presentation ≥ 12 h after symptom onset were exclusion criteria.

2.2. Study Procedure, Study Materials and Imaging Analysis

Medical therapy, including the use of antithrombotic therapy, occurred per current clinical practice guidelines [13]. PCI was performed using standard techniques at the discretion of the operator.

Intravascular imaging was intentionally performed with the multifrequency high‐definition (40–60 MHz) IVUS system (Kodama, ACIST Medical Systems, Eden Prairie, Minnesota, USA), while stenting was performed with the Firehawk Sirolimus Target Eluting Coronary Stent System (Microport, Shanghai, China). Pullbacks were conducted at an automated pullback speed of 2.5 mm/s, acquiring 60 frames per second (24 frames per mm).

In brief, each patient underwent the following IVUS assessments: (1) A “pre‐intervention IVUS pullback” directly after vessel wiring (i.e., before any lesion preparation, including aspiration thrombectomy); (2) a “post‐intervention IVUS pullback” following PCI (preferably after angiographically successful results, starting at least 2 cm distal to the most distal stent edge or treated segment); (3) a “post‐optimization IVUS pullback“ in case PCI optimization was performed. The predefined criteria for IVUS‐guided optimization were as follows: (1) a residual focal lesion proximal or distal of the stented segment with either a percentage area stenosis ≥ 75% or a percentage area stenosis of 50%−75% accompanied by a minimal lumen area (MLA) of < 2.5 mm²; (2) edge dissections involving the media with a length of >3.0 mm; (3) underexpansion with a minimal stent area (MSA) < 5.0 mm² and < 90% stent expansion (based on the MLA of the distal stent edge reference segment [5 mm]); (4) an average plaque burden > 50% at the proximal or distal stent edge reference segments (5 mm). The PCI result was considered “optimal” if all IVUS criteria were met. Given the uncertain clinical relevance of stent malapposition and thrombus protrusion and their association with subsequent adverse events, these findings were systematically recorded but were not included among the predefined IVUS criteria for PCI optimization. A detailed description of the protocolized use of IVUS, all quantitative and qualitative intravascular imaging definitions, as well as the results of the pre‐intervention IVUS pullbacks (i.e., culprit lesion findings) have been published previously [18, 19].

Quantitative and qualitative IVUS measurements were performed systematically by the Erasmus University Medical Center academic corelab, using dedicated software (QCU‐CMS, Leiden University Medical Center, LKEB, Division of Imaging Processing, V.4.69) and according to a previously defined methodology [19, 21].

2.3. Study Endpoints

The primary endpoint was TVF at 12 months, defined as a composite of cardiovascular death, target vessel myocardial infarction (TVMI) and clinically‐driven target vessel revascularization (TVR) [22]. The secondary outcome of interest was the presence of IVUS‐guided PCI optimization, defined as additional treatment (including balloon dilatation, stent placement or aspiration thrombectomy) following the “post‐intervention IVUS pullback.”

Other endpoints included TVF at 30 days, as well as major adverse cardiovascular events (MACE) and stent thrombosis at 30 days and 12 months [19, 22]. MACE was a composite of all‐cause mortality, any myocardial infarction and repeat revascularization (not including a staged PCI or coronary artery bypass graft surgery for multivessel disease).

2.4. Data Management and Follow‐Up

All study data were stored in a dedicated local research database. Follow‐up was obtained using an in‐house developed dedicated platform (CathSuite), facilitating online patient‐reported outcome measurements, renouncing the need for sending printed questionnaires, standardized telephone calls, or outpatient clinic visits [19]. All events were adjudicated by an independent clinical event committee.

2.5. Sample Size

With 400 to 500 STEMI patients undergoing primary PCI annually at our hospital, and assuming that approximately 40% of patients would be eligible for inclusion (due to exclusion criteria, lack of informed consent, or participation in other registered cardiovascular trials), the sample size of 200 patients was chosen as a pragmatic target allowing both calculation of an acceptably narrow confidence interval (CI) for the primary endpoint, as well as completion of study inclusion within 12−18 months. Assuming a 12‐month TVF rate of 10% as a conservative estimate, a sample size of 200 patients would allow for a 95% CI ranging from 6% to 14% [19].

2.6. Statistical Analysis

Categorical variables are presented as counts and percentages and compared using Pearson's Chi‐Square test or Fisher's exact test (as appropriate). Continuous variables are reported as mean ± standard deviation (SD) for normally distributed variables and as medians with 25th−75th percentiles for non‐normally distributed variables. The Shapiro−Wilk test was used to investigate whether continuous variables were normally distributed. Changes in continuous and categorical IVUS measurements between post‐intervention and post‐optimization IVUS pullbacks were investigated using paired t‐tests (normally distributed variables), Wilcoxon signed‐rank tests (non‐normally distributed variables) and the McNemar test (binary variables) as appropriate.

TVF is presented as a count with percentage, including the Clopper–Pearson 95% CI for a binomial proportion. Univariable Cox proportional hazards regression analysis was performed to assess the association between (sub)optimal PCI based on the predefined IVUS criteria and TVF.

SPSS version 28 was used for statistical analysis. A 2‐sided p < 0.05 was considered statistically significant.

3. Results

3.1. Study Population and Patient Characteristics

From November 2020 to February 2022, a total of 200 STEMI patients were included (Supporting Information S1: Figure 1). Mean (±SD) age was 62.1 (±12.5) years, and 138 (69.0%) patients were male (Table 1). In brief, 22 (11.0%) patients had diabetes (medication dependent), and 36 (18.0%) patients had prior coronary revascularization. The median (25th−75th percentiles) time from symptom onset to start of the procedure was 124.0 (89.5−219.5) min.

Table 1.

Baseline characteristics.

Variable	n = 200
Age (years)	62.1 ± 12.5
Male gender	138 (69.0)
Cardiovascular risk factors
Hypertension	84 (42.0)
Hypercholesterolemia	62 (31.0)
Diabetes, medication dependent	22 (11.0)
Active smoker	93 (46.5)
Family history	59 (29.5)
Cardiovascular history
Prior myocardial infarction	25 (12.5)
Prior revascularization	36 (18.0)
Time from symptom onset to start procedure (min)	124 (90−220)
Pre procedural use of oral anticoagulation
Aspirin	198 (99.0)
P2Y12 inhibitor	200 (100.0)
Clopidogrel	8 (4.0)
Prasugrel	135 (67.5)
Ticagrelor	57 (28.5)

Note: Values are mean ± standard deviation, median (25th−75th percentiles) or n (%).

3.2. Angiographic and Procedural Characteristics

The left anterior descending (LAD) was the culprit vessel in 88 (44.0%) of the patients (Table 2). In total, 94 (47.0%) patients presented with Thrombolysis in Myocardial Infarction (TIMI) flow grade 0 and 19 (9.5%) patients with stent thrombosis (Supporting Information S1: Table 1).

Table 2.

Procedural characteristics.

Variable	n = 200
Radial access	199 (99.5)
Culprit vessel
RCA	88 (44.0)
LAD/D	88 (44.0)
LCx/OM/Anterolateral	24 (12.0)
Preintervention IVUS pullback performeda	189 (94.5)
Lesion preparation
Predilatation	82 (41.0)
Aspiration thrombectomy	40 (20.0)
Treatment strategy
Balloon dilatation only	7 (3.5)
Drug‐eluting stent	193 (96.5)
Direct stenting	111/193 (57.5)
Total number of stents	1.0 (1.0−2.0)
Total stent length (mm)	38.0 (26.0−51.0)
Max stent diameter (mm)	3.5 (3.0−4.0)
Type of drug‐eluting stent
Microport firehawk	173/193 (89.6)
Other	20/193 (10.4)
Postdilatation	157/193 (81.3)
NC balloon	139/157 (88.5)
Per‐procedural use of glycoprotein IIb/IIIa antagonist	48 (24.0)
Final TIMI 3 flow	175 (87.5)
Final myocardial blush grade
Not assessable	26 (13.0)
Grade 0	5 (2.5)
Grade 1	31 (15.5)
Grade 2	85 (42.5)
Grade 3	53 (26.5)
Complete ST‐segment resolution (>70%)	73 (36.5)
Multivessel disease	60 (30.0)
Immediate PCI non‐culprit vessel	36/60 (60.0)
IVUS‐guided	26/36 (72.2)
Staged PCI non‐culprit vessel	12/60 (20.0)
IVUS‐guided	5/12 (41.7)
Staged CABG	4/60 (6.7)
Procedure time (min)	55.5 (41.8−72.0)
Contrast use (mL)	100.0 (80.0−140.0)

Note: Values are median (25th−75th percentiles) or n (%). Abbreviations: CABG = coronary artery bypass graft; D = diagonal; IVUS = intravascular ultrasound; LAD = left anterior descending; LCx = left circumflex; NC = non‐compliant; OM = obtuse marginal; PCI = percutaneous coronary intervention; RCA = right coronary artery; TIMI = thrombolysis in myocardial infarction.

^aDirectly after vessel wiring, so before any lesion preparation (i.e., predilatation, aspiration thrombectomy or stent placement).

A pre‐intervention IVUS pullback (i.e., before any lesion preparation) was performed in 189 (94.5%) patients, followed by predilatation in 41.0% and aspiration thrombectomy in 20.0% (Table 2). In total, 193 (96.5%) patients were treated with drug‐eluting stents, followed by postdilatation in 81.3%. In 48 (24.0%) patients, a glycoprotein IIb/IIIa antagonist was used. Final TIMI flow grade 3 was observed in 175 (87.5%) patients.

3.3. Post‐Intervention IVUS Pullback Findings

A fully analyzable post‐intervention IVUS pullback was available in 95% of cases. The median total stent length was 34.3 (23.0−43.3) mm and median MSA was 5.7 (4.5−7.2) mm² (Table 3). A residual focal lesion was observed in 7.9%, a submedial edge dissection > 3 mm in 4.7%, underexpansion in 8.4%, and edge plaque burden > 50% in 40.5% (Figure 1). Furthermore, malapposition was found in 15.8% and thrombus protrusion in 53.2%.

Table 3.

Postintervention IVUS characteristics.

Variable	n = 190
Proximal reference segment
Average plaque burden (%)	44.5 ± 10.2
> 50%	52/190 (27.4)
Edge dissection	10/190 (5.3)
Submedial	3/10 (30.0)
Length > 3.0 mm	3/3 (100.0)
Residual focal lesiona	4/190 (2.1)
Stented/treated segment
Total length (mm)	34.3 (23.0−43.3)
Minimal stent area (mm2)	5.7 (4.5−7.2)
< 5.0 mm2	68/190 (35.8)
Stent expansion (%)b	117.6 (94.9−145.3)
< 90%	41/190 (21.6)
Thrombus protrusion	101/190 (53.2)
Malapposition	30/190 (15.8)
Distal reference segment
Average plaque burden (%)	39.5 (29.3−48.3)
> 50%	41/190 (21.6)
Edge dissection	22/190 (11.6)
Submedial	12/22 (54.5)
Length > 3.0 mm	7/12 (58.3)
Residual focal lesiona	11/190 (5.8)

Note: Values are mean ± standard deviation, median (25th−75th percentiles) or n (%).

Abbreviation: IVUS = intravascular ultrasound.

^aLesion in the reference or rest segment with a percentage area stenosis ≥ 75% or percentage area stenosis 50%−75% with a minimal lumen area < 2.5 mm²;

^bCalculated as minimal stent area/minimal lumen area distal reference segment * 100%.

Figure 1.

Main post‐intervention and post‐optimization IVUS pullback findings, including the predefined IVUS criteria for PCI optimization. Values are counts with percentages. The yellow arrow indicates a submedial edge dissection. The yellow asterisks show a submedial hematoma. The pink arrows indicate thrombus protrusion. *Performed and fully analyzable. DR = distal reference segment, IVUS = intravascular ultrasound, PCI = percutaneous coronary intervention, PR = proximal reference segment. [Color figure can be viewed at wileyonlinelibrary.com]

Optimal stenting criteria were not met in 91/190 (47.9%) patients, predominantly due to residual plaque burden > 50% at either the proximal or distal stent edge (84.6%).

3.4. IVUS‐Guided Optimization

IVUS‐guided optimization was performed in 78/190 (41.1%) patients (Figure 2).

Figure 2.

Treatment strategy in the SPECTRUM study, including IVUS‐guided optimization and final PCI results based on the IVUS criteria. IVUS = intravascular ultrasound, PCI = percutaneous coronary intervention, STEMI = ST‐segment elevation myocardial infarction. [Color figure can be viewed at wileyonlinelibrary.com]

PCI optimization was performed in 29/99 (29.3%) patients despite an IVUS‐defined optimal PCI result on post‐intervention assessment, and consisted of postdilatation in 25/29 patients (86.2%). Conversely, PCI optimization was performed in 49/91 (53.8%) patients who did not meet the IVUS‐defined optimal stenting criteria on post‐intervention assessment. In these cases, optimization was achieved by means of postdilatation in 45/49 patients (91.8%) and additional stenting in 32/49 patients (65.3%) (Figure 2).

Of interest, PCI optimization was performed despite angiographically successful PCI (i.e., TIMI flow grade 3 with <30% residual stenosis) in 37/78 (47.4%) patients, after angiographically unsuccessful PCI (e.g., no TIMI flow grade 3) in 21/78 (26.9%) patients, and without knowledge of the angiographic result (purely based on post‐intervention IVUS) in 20/78 (25.6%) patients. In 24/37 (64.9%) patients with an angiographically successful PCI result but suboptimal IVUS findings, triggers for PCI optimization were a residual focal lesion in 25.0%, a submedial edge dissection > 3 mm in 4.2%, underexpansion in 20.8%, and edge plaque burden > 50% in 79.2%. Optimization was achieved by means of postdilatation in 91.7% and additional stenting in 58.3%.

3.5. Post‐Optimization IVUS Pullback Findings

A fully analyzable post‐optimization IVUS pullback was available in 62/78 (79.5%) patients (Figure 2). The median total stent length was 37.8 (26.8−50.0) mm and median MSA was 5.7 (4.1−7.5) mm² (Table 4). The mean increase in MSA was 0.72 ± 0.79 mm² (p < 0.001). A residual focal lesion was observed in 1.6%, a submedial edge dissection > 3 mm in 1.6%, underexpansion in 4.8%, and plaque burden > 50% in 27.4% (Figure 1). Furthermore, malapposition was found in 9.7% and thrombus protrusion in 50.0%.

Table 4.

Post‐optimization IVUS characteristics.

Variable	n = 62
Proximal reference segment
Average plaque burden (%)	43.9 ± 10.3
> 50%	12/62 (19.4)
Edge dissection	0/62 (0.0)
Submedial	NA
Length > 3.0 mm	NA
Residual focal lesiona	0/62 (0.0)
Stented/treated segment
Total length (mm)	37.8 (26.8−50.0)
Minimal stent area (mm2)	5.7 (4.1−7.5)
< 5.0 mm2	26/62 (41.9)
Increase (mm2)b	0.72 ± 0.79
Stent expansion (%)c	112.4 (99.6−131.5)
< 90%	9/62 (14.5)
Increase (%)b	11.0 (−5.9 to 23.3)
Thrombus protrusion	31/62 (50.0)
Malapposition	6/62 (9.7)
Distal reference segment
Average plaque burden (%)	34.7 (27.4−46.4)
> 50%	7/62 (11.3)
Edge dissection	7/62 (11.3)
Submedial	4/7 (57.1)
Length > 3.0 mm	1/4 (25.0)
Residual focal lesiona	1/62 (1.6)

Note: Values are mean ± standard deviation, median (25th−75th percentiles) or n (%).

Abbreviation: IVUS = intravascular ultrasound.

^aLesion in the reference or rest segment with a percentage area stenosis ≥ 75% or percentage area stenosis 50%−75% with a minimal lumen area < 2.5 mm²;

^bOnly calculated in patients with postdilatation of initial stent without additional stent placement. p value for increase in minimal stent area < 0.001. p value for increase in stent expansion = 0.031;

^cCalculated as minimal stent area/minimal lumen area distal reference segment * 100%.

Following PCI optimization, optimal stenting criteria were not met in 18/62 (29.0%) patients, predominantly due to residual plaque burden > 50% at either the proximal or distal stent edge (94.4%).

Following IVUS‐guided PCI optimization, the overall rate of patients with an optimal PCI result based on the predefined criteria increased from 52.1% (99/190 patients) to 65.5% (114/174 patients) (Figure 2, p < 0.001). The success rate for IVUS‐guided PCI optimization was highest for a residual focal lesion (89.9%, p < 0.001) and lowest for plaque burden > 50% (48.5%, p = 0.174) (Supporting Information S1: Figure 2).

3.6. Major Procedural Complications and Clinical Outcomes

No reflow (TIMI flow grade 0 or 1) assessed during the final angiographic imaging was present in four patients (2.0%), and vessel perforations were observed in two patients (1.0%) (Supporting Information S1: Table 2).

Follow‐up was complete for 194 patients (97.0%). TVF at 12 months occurred in six patients (3.0%, 95% CI 1.1%−6.4%), while cardiac death, TVMI and TVR occurred in two patients (1.0%), four patients (2.0%), and three patients (1.5%), respectively (Table 5).

Table 5.

Clinical outcomes at 30 days and 12 months.

Variable	n = 200
30 days
Target vessel failure	4 (2.0)
Cardiac death	2 (1.0)
Target vessel myocardial infarction	2 (1.0)
Target vessel revascularization	1 (0.5)
Major adverse cardiovascular event	4 (2.0)
All‐cause mortality	2 (1.0)
Any myocardial infarction	2 (1.0)
Any unplanned repeat revascularization	1 (0.5)
Stent thrombosis	1 (0.5)
12 months
Target vessel failure	6 (3.0)
Cardiac death	2 (1.0)
Target vessel myocardial infarction	4 (2.0)
Target vessel revascularization	3 (1.5)
Major adverse cardiovascular event	7 (3.5)
All‐cause mortality	3 (1.5)
Any myocardial infarction	4 (2.0)
Any unplanned repeat revascularization	3 (1.5)
Stent thrombosis	1 (0.5)

Note: Values are n (%). The individual components of TVF are not mutually exclusive, as some patients experienced more than one qualifying event. Therefore, the total number of events may exceed the number of patients with TVF.

Optimal PCI based on IVUS was not significantly associated with lower TVF at 12 months (2.6% vs. 3.3%; HR 0.78, 95% CI 0.13−4.69, p = 0.79).

4. Discussion

The SPECTRUM study provides a dedicated evaluation of the protocolized use of IVUS to guide primary PCI in patients presenting with STEMI. The main findings can be summarized as follows: (1) IVUS‐guided PCI was safe and resulted in low TVF rates at 12 months (3%); (2) IVUS‐guided optimization was performed in 41.1%; (3) IVUS‐guided optimization significantly increased the number of cases with an optimal PCI result (from 52.1% to 65.5%) (Central Illustration 1).

Central Illustration 1.

The SPECTRUM study investigated the protocolized use of IVUS‐guided primary PCI in patients presenting with STEMI. IVUS‐guided PCI was safe and resulted in low TVF rates at 12 months (3%). Furthermore, IVUS‐guided optimization was performed in 41.1% and significantly increased the number of cases with an optimal PCI result (52.1% to 65.5%; p < 0.001). [Color figure can be viewed at wileyonlinelibrary.com]

The 2023 ESC guidelines for the management of ACS provide a class IIa indication for the use of intravascular imaging to guide PCI of a clear culprit lesion in patients presenting with ACS [13]. However, data to support the use of IVUS in this subset of patients are mostly derived from subgroup analyses of large trials in which STEMI patients were vastly underrepresented or excluded. Several studies have proposed that the beneficial impact of IVUS‐guided PCI can be extended to patients with acute myocardial infarction, and more specifically to STEMI [9, 10, 11]. In the recently published IVUS‐ACS trial, which compared IVUS‐ versus angiography‐guided PCI in 3505 ACS patients, the beneficial impact of IVUS guidance on 12‐month TVF persisted in a subgroup analysis including 973 STEMI patients (6.0% vs. 11.5% [HR 0.54, 95% CI 0.34−0.85]) [12]. Although the trial represents a stronger dataset in terms of design and statistical power, it unfortunately refrained from providing detailed insights into the actual mechanisms by which IVUS improved outcomes.

Primary PCI has been recognized as one of the most challenging PCI scenarios for several reasons: (1) presence of spasm with an inherent risk of stent undersizing; (2) presence of (spontaneous) dissection; (3) high thrombus burden and no‐reflow; (4) presence of complex lesion morphology, including plaque ruptures, calcified nodules and stent thrombosis [13, 14, 15, 16, 18]. The latter strengthens the rationale for IVUS guidance to assure optimal PCI results. More specifically, IVUS allows detailed culprit lesion characterization, including the visualization of both calcium and plaque rupture, and the assessment of thrombus [17, 18]. These insights allow tailored use of aspiration thrombectomy, plaque preparation and calcium modification, ensure true lumen stenting, and could potentially guide the use of per‐procedural glycoprotein IIb/IIIa receptor antagonists. Additionally, post‐intervention pullbacks allow PCI optimization specifically tailored to a primary PCI setting, including restrictive bailout stenting and a less aggressive postdilatation approach in case of much thrombus protrusion or no‐reflow.

In the present study, IVUS‐guided optimization was performed in 41.1% of patients. In almost 3 out of 4 patients, additional treatment occurred despite an angiographically successful PCI or without knowledge of the angiographic result. This finding clearly demonstrates how IVUS augments angiography by enabling the identification of optimization targets and reducing contrast use. Several remarkable imaging findings and subsequent optimization strategies should be discussed. First, post‐intervention optimal stenting criteria were not achieved in 47.9% of patients, mostly due to a remaining plaque burden > 50% at the stent edges (84.6%). In over half of these cases (53.8%), further optimization was performed, resulting in a final optimal stenting result as defined by IVUS in 65.6%. Conversely, it remains intriguing that IVUS guidance did not prevent geographic miss in 84.6% of patients with a suboptimal post‐intervention result, and operators refrained from performing optimization in 46.2%. The latter is in line with previous work from our group in more stable patients enrolled within the randomized FFR REACT trial, in which optimal IVUS criteria following optimization were not met in 80.2%, largely due to a remaining plaque burden > 50% at the edges in 75.6% [23]. A potential explanation could lie in the evaluation of edge plaque composition, which, regrettably, was not included in the scope of this study. Second, in patients who did meet all the predefined IVUS criteria following initial PCI, additional PCI optimization was still performed in 29.3%. Optimization mostly consisted of postdilatation only, in cases in which the mean MSA was 5.72 mm², which may have been considered suboptimal in patients in whom larger stent sizes were used. This finding is not surprising given the fact that IVUS guidance is known to result in higher postdilatation rates [3, 24]. Third, direct stenting rate was as high as 57.5%, aspiration thrombectomy was performed in 7.7% of patients following initial PCI, and in 24.0% of patients glycoprotein IIb/IIIa antagonists were used. The latter, in part driven by IVUS‐derived findings, could have contributed to a final TIMI flow grade 0 or 1 in merely 2.0% of cases. Larger studies are needed to investigate the association between non‐calcified plaque amenable to direct stenting, high thrombus burden, thrombus protrusion, malapposition, and subsequent no reflow, in relation to IVUS‐guided treatment strategies.

As mentioned, in the present study, the rate of IVUS‐defined optimal stenting criteria significantly augmented to 65.5% following PCI optimization. This final number is significantly lower as compared to the 79.9% of patients with an optimal PCI result within the IVUS‐ACS trial, a difference that may be explained by the different threshold for stent‐edge plaque burden (50% vs. 55%) [12]. Although this difference may seem trivial, at least 25 patients within the present study ended with an average stent‐edge plaque burden between 50% and 55%, indicating that the proportion of patients with an optimal PCI result would have been higher if a less strict threshold had been applied. Conversely, within our study, IVUS triggered treatment of residual focal lesions which were not readily apparent on angiography in 26.5% of cases. Hypothetically, this finding may have contributed to the lower‐than‐expected TVF rates observed. However, this study was not powered to assess whether IVUS‐guided optimization of specific predefined targets was associated with improved clinical outcomes.

Acknowledging the limited sample size of our study, the TVF rate at 12 months was merely 3.0% whereas TVMI and TVR were observed in only 2.0% and 1.5%, respectively, with no major procedural safety events noted. Of note, these results should be interpreted in light of primary PCI care in an urban Dutch area with streamlined logistics resulting in a median ischemia time of 124 min. Substantiated by an analysis of Sharp et al. demonstrating that IVUS guidance in ACS is highly cost‐effective, and the eagerly awaited results of the ongoing iSTEMI trial (NCT04775914), future guidelines may further strengthen the recommendations of IVUS in STEMI patients [25].

4.1. Limitations

The main limitation of our study is its single‐arm observational design, precluding a direct comparison with angiography‐guided primary PCI. All potential types of bias inherent to this design should be considered. In particular, not all consecutive eligible patients were included, which might limit the generalizability of our findings due to a potentially selected population. Furthermore, although institutional research support was provided by the manufacturers of the IVUS system and stent used in this study, the absence of an angiography‐guided comparator limited our ability to distinguish the independent contribution of IVUS‐guided optimization from potential effects related to the stent platform or institutional expertise.

Second, study procedures were performed at the Erasmus University Medical Center, a high‐volume, “level 3,” catheterization laboratory with extensive expertise in intravascular imaging. We acknowledge that the implementation of IVUS‐guided primary PCI, particularly when including multiple IVUS pullbacks, may be challenging in routine clinical practice due to factors such as limited operator expertise, procedural time constraints, and resource limitations. Developments of AI‐based technologies are currently being implemented in widely used imaging systems and may enhance the feasibility of careful examination of multiple pullbacks.

Third, in certain cases operators deviated from the protocolized use of IVUS, and adherence to the predefined criteria for PCI optimization was not uniform. We believe this reflects real‐world clinical practice.

Fourth, since the use of nitroglycerine was not protocolized, vasospasm may have influenced vessel and lumen parameters with a potential impact on subsequent stent sizing and IVUS‐defined results.

Finally, although clinically reassuring, the observed TVF rate of 3.0% was substantially lower than the anticipated 10% used for sample size calculation, resulting in reduced statistical power. The low number of events precluded subgroup analyses as well as multivariable adjustment to assess the association between IVUS findings and TVF. The in‐house CathSuite follow‐up platform, based on online patient‐reported outcome measurements without standardized telephone calls or clinical visits, may have resulted in underreporting of clinical outcomes.

5. Conclusions

SPECTRUM is the first dedicated prospective study demonstrating the potential of IVUS to optimize outcomes in a primary PCI setting. IVUS guidance in primary PCI was safe, significantly increased the number of STEMI patients with an optimal PCI result, and resulted in low rates of TVF at 12 months.

Conflicts of Interest

Joost Daemen has received institutional grant/research support from Abbott Vascular, ACIST Medical, Boston Scientific, Medtronic, Pie Medical, and ReCor Medical, and consultancy and speaker fees from Abbott Vascular, ACIST Medical, Boston Scientific, Cardialysis BV, CardiacBooster, Kaminari Medical, Medtronic, Pie Medical, ReCor Medical, Sanofi, and Siemens Health Care. Nicolas van Mieghem has received institutional research grant support from Abbott Vascular, Biotronik, Boston Scientific, Daiichi Sankyo, Edwards Lifesciences, and Medtronic, and consultancy fees from Abbott, Abiomed, Amgen, Anteris, Boston Scientific, Daiichi Sankyo, JenaValve, Medtronic, PulseCath BV, and Teleflex. Karim Mahmoud has received educational grants from Boston Scientific and Novartis. Roberto Diletti has received institutional research grants from ACIST Medical, Biotronik, Boston Scientific and Medtronic. Rutger‐Jan Nuis has received research grant support from Merill and Vifor Pharma, and consulting fees from Abbott, Boston Scientific, and Edwards Lifesciences. The other authors declare no conflicts of interest.

Supporting information

Figure S1: Flowchart for study participants.

Figure S2: PCI optimization success rates for each of the predefined IVUS criteria.

Table S1: Baseline angiographic culprit lesion characteristics.

Table S2: Major intraprocedural complications.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.