Intravascular imaging-guided percutaneous coronary intervention for heavily calcified coronary lesions: a systematic review and meta-analysis.

Although multiple randomized clinical trials (RCTs) have shown that intravascular imaging (IVI)-guided percutaneous coronary intervention (PCI) is associated with improved clinical outcomes compared with angiography-guided PCI, its benefits specifically in calcified coronary lesions is unclear due to the small number of patients included in individual trials. We performed a meta-analysis of RCTs to investigate benefits of IVI-guided PCI compared with angiography-guided PCI in heavily calcified coronary lesions. The primary endpoint was major adverse cardiac events (MACE), a composite of cardiac death, target-vessel or target-lesion myocardial infarction, and target-vessel or target lesion revascularization. Pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated by using a random-effects meta-analysis based on the restricted maximum likelihood method. A search PubMed, EMBASE, and Cochrane Library from their inception to January 2024 identified 4 trials that randomized 1319 patients with angiographically moderate or severe or severe coronary calcification to IVI-guided (n = 702) vs. angiography-guided PCI (n = 617). IVI-guided PCI resulted in a significantly lower odds of MACE (OR 0.57, 95% CI 0.40-0.80) compared with angiography-guided PCI at a weighted median follow-up duration of 27.3 months. There was no evidence of heterogeneity among the studies (I2 = 0.0%), and included trials were judged to be low risk of bias. Compared with angiography-guided PCI, IVI-guided PCI was associated with a significantly lower MACE in angiographically heavily calcified coronary lesions.

OCT-Guided versus Angiography-Guided Coronary Stent Implantation in Complex Lesions: An ILUMIEN IV Substudy.

BACKGROUND: ILUMIEN IV was the first large-scale, multicenter, randomized trial comparing optical coherence tomography (OCT)-guided versus angiography-guided stent implantation in patients with high-risk clinical characteristics and/or complex angiographic lesions. OBJECTIVE: Here, we aimed to specifically examine outcomes in the complex angiographic lesions subgroup. METHODS: From the original trial population (n=2487), high-risk patients without complex angiographic lesions were excluded (n=514). Complex angiographic lesion characteristics included 1) long or multiple lesions with intended total stent length ≥28 mm; 2) bifurcation lesion with intended two-stent strategy; 3) severely calcified lesion; 4) chronic total occlusion; or 5) in-stent restenosis. The study endpoints were 1) final minimal stent area (MSA); 2) 2-year composite of serious major adverse cardiovascular events (MACE; cardiac death, target-vessel myocardial infarction (MI), or stent thrombosis); and 3) 2-year effectiveness, defined as target-vessel failure (TVF), a composite of cardiac death, target-vessel MI, or ischemia-driven target-vessel revascularization. RESULTS: The post-PCI MSA was larger in the OCT- (n=992) versus angiography-guided (n=981) group (5.56±1.95 versus 5.26±1.81mm2; difference, 0.30; 95% confidence interval [CI], 0.14-0.47; P<0.001). Compared with angiography-guided PCI, OCT-guided PCI resulted in a lower risk of serious MACE (3.1% versus 4.9%; hazard ratio [HR], 0.63; 95% CI, 0.40-0.99; P=0.04). TVF was not significantly different between groups (7.3% versus 8.8%; HR, 0.82; 95% CI, 0.59-1.12; P=0.20). CONCLUSIONS: In complex angiographic lesions, OCT-guided PCI led to a larger MSA and reduced the serious MACE composite of cardiac death, target-vessel MI, or stent thrombosis compared with angiography-guided PCI at 2 years, but did not significantly improve TVF.

Calcified Nodule in Percutaneous Coronary Intervention: Therapeutic Challenges.

Calcified nodules (CNs) are among the most challenging lesions to treat in contemporary percutaneous coronary intervention. CNs may be divided into 2 subtypes, eruptive and noneruptive, which have distinct histopathological and prognostic features. An eruptive CN is a biologically active lesion with a disrupted fibrous cap and possibly adherent thrombus, whereas a noneruptive CN has an intact fibrous cap and no adherent thrombus. The use of intravascular imaging may allow differentiation between the 2 subtypes, thus potentially guiding treatment strategy. Compared with noneruptive CNs, eruptive CNs are more likely to be deformable, resulting in better stent expansion, but are paradoxically associated with worse clinical outcomes, in part because of their frequent initial presentation as an acute coronary syndrome and subsequent reprotrusion of the CN into the vessel lumen through the stent struts. Pending the results of ongoing studies, a tailored therapeutic approach based on the distinct features of the different CNs may be of value.

Distinct Challenges of Eruptive and Non-Eruptive Calcified Nodules in Percutaneous Coronary Intervention.

PURPOSE OF REVIEW: To provide a summary of prevalence, pathogenesis, and treatment of coronary calcified nodules (CNs). RECENT FINDINGS: CNs are most frequently detected at the sites of hinge motion of severely calcified lesions such as in the middle segment of right coronary artery and left main coronary bifurcation. On histopathology, CNs exhibit two distinctive morphologies: eruptive and non-eruptive. Eruptive CNs, which have a disrupted fibrous cap with adherent thrombi, are biologically active. Non-eruptive CNs, which have an intact fibrous cap without thrombi, are biologically inactive, representing either healed eruptive CNs or protrusion of calcium due to plaque progression. Recent studies using optical coherence tomography (OCT) have shown a difference in the mechanism of stent failure in the two subtypes, demonstrating early reappearance of eruptive CNs in the stent (at ~ 6 months) as a unique mechanism of stent failure that does not seem to be preventable by simply achieving adequate stent expansion. The cause of CN reappearance in stent is not known and could be due to acute or subacute intrusion or continued growth of the CN. Whether modification of CN is needed, the most effective calcium modification modality and effectiveness of stent implantation in eruptive CNs has not been elucidated. In this review, we discuss pathogenesis of CNs and how intravascular imaging can help diagnose and manage patients with CNs. We also discuss medical and transcatheter therapies beyond conventional stent implantation for effective treatment of eruptive CNs that warrant testing in prospective studies.

Prevalence and anatomical factors associated with stent under-expansion in non-severely calcified lesions.

BACKGROUND: Stent underexpansion, typically related to lesion calcification, is the strongest predictor of adverse events after percutaneous coronary intervention (PCI). Although uncommon, underexpansion may also occur in non-severely calcified lesions. AIM: We sought to identify the prevalence and anatomical characteristics of underexpansion in non-severely calcified lesions. METHODS: We included 993 patients who underwent optical coherence tomography-guided PCI of 1051 de novo lesions with maximum calcium arc <180°. Negative remodeling (NR) was the smallest lesion site external elastic lamina diameter that was also smaller than the distal reference. Stent expansion was evaluated using a linear regression model accounting for vessel tapering; underexpansion required both stent expansion <70% and stent area <4.5mm2. RESULTS: Underexpansion was observed in 3.6% of non-heavily calcified lesions (38/1051). Pre-stent maximum calcium arc and thickness were greater in lesions with versus without underexpansion (median 119° vs. 85°, p = 0.002; median 0.95 mm vs. 0.78 mm, p = 0.008). NR was also more common in lesions with underexpansion (44.7% vs. 24.5%, p = 0.007). In the multivariable logistic regression model, larger and thicker eccentric calcium, mid left anterior descending artery (LAD) location, and NR were associated with underexpansion in non-severely calcified lesions. The rate of underexpansion was especially high (30.7%) in lesions exhibiting all three morphologies. Two-year TLF tended to be higher in underexpanded versus non-underexpanded stents (9.7% vs. 3.7%, unadjusted hazard ratio [95% confidence interval] = 3.02 [0.92, 9.58], p = 0.06). CONCLUSION: Although underexpansion in the absence of severe calcium (<180°) is uncommon, mid-LAD lesions with NR and large and thick eccentric calcium were associated with underexpansion.

Optical Coherence Tomography-Based Functional Stenosis Assessment: FUSION-A Prospective Multicenter Trial.

BACKGROUND: Intravascular imaging and intracoronary physiology may both be used to guide and optimize percutaneous coronary intervention; however, they are rarely used together. The virtual flow reserve (VFR) is an optical coherence tomography (OCT)-based model of fractional flow reserve (FFR) facilitating the assessment of the physiological significance of coronary lesions. We aimed to validate the VFR assessment of intermediate coronary artery stenoses. METHODS: FUSION (Validation of OCT-Based Functional Diagnosis of Coronary Stenosis) was a multicenter, prospective, observational study comparing OCT-derived VFR to invasive FFR. VFR was mathematically derived from a lumped parameter flow model based on 3-dimensional lumen morphology. Patients undergoing coronary angiography with intermediate angiographic stenosis (40%-90%) requiring physiological assessment were enrolled. Investigational sites were blinded to the VFR analysis, and all OCT and FFR data were reviewed by an independent core laboratory. The coprimary end points were the sensitivity and specificity of VFR against FFR as the reference standard, each of which was tested against prespecified performance goals. RESULTS: After core laboratory review, 266 vessels in 224 patients from 25 US centers were included in the analysis. The mean angiographic diameter stenosis was 65.5%±14.9%, and the mean FFR was 0.83±0.11. Overall accuracy, sensitivity, and specificity of VFR versus FFR using a binary cutoff point of 0.80 were 82.0%, 80.4%, and 82.9%, respectively. The 97.5% lower confidence bound met the prespecified performance goal for sensitivity (71.6% versus 70%; P=0.01) and specificity (76.6% versus 75%; P=0.01). The area under the curve was 0.88 (95% CI, 0.84-0.92; P<0.0001). CONCLUSIONS: OCT-derived VFR demonstrates high sensitivity and specificity for predicting invasive FFR. Integrating high-resolution intravascular imaging with imaging-derived physiology may provide synergistic benefits as an adjunct to percutaneous coronary intervention. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04356027.

Impact of Incomplete Revascularization After PCI in Left Main Disease: The EXCEL Trial.

BACKGROUND: The importance of complete revascularization after percutaneous coronary intervention (PCI) in patients with left main coronary artery disease is uncertain. We investigated the clinical impact of complete revascularization in patients with left main coronary artery disease undergoing PCI in the EXCEL trial (Evaluation of XIENCE Versus Coronary Artery Bypass Surgery for Effectiveness of Left Main Revascularization). METHODS: Composite rates of death or myocardial infarction (MI) following PCI during 5-year follow-up were examined in 903 patients based on core laboratory definitions of anatomic and functional complete revascularization, residual SYNTAX score (The Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery), and residual Jeopardy Score (rJS). RESULTS: The risk of death or MI did not vary based on anatomic, functional, or residual SYNTAX score complete revascularization but did differ according to the rJS (5-year rates 17.6%, 19.5%, and 38.9% with rJS 0, 2, and ≥4, respectively; P=0.006). The higher rate of death or MI with rJS≥4 versus rJS≤2 was driven conjointly by increased mortality (adjusted hazard ratio, 2.29 [95% CI, 1.11-4.71]; P=0.02) and spontaneous MI (adjusted hazard ratio, 2.89 [95% CI, 1.17-7.17]; P=0.02). The most common location for untreated severe stenoses in the rJS≥4 group was the left circumflex artery (LCX), and the post-PCI absence, compared with the presence, of any untreated lesion with diameter stenosis ≥70% in the LCX was associated with reduced 5-year rates of death or MI (18.9% versus 35.2%; hazard ratio, 0.48 [95% CI, 0.32-0.74]; P<0.001). The risk was the highest for residual ostial/proximal LCX lesions. CONCLUSIONS: Among patients undergoing PCI in EXCEL trial, incomplete revascularization according to the rJS was associated with increased rates of death and spontaneous MI. Post-PCI untreated high-grade lesions in the LCX (especially the ostial/proximal LCX) drove these outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01205776.

Intravascular imaging-guided coronary drug-eluting stent implantation: an updated network meta-analysis.

BACKGROUND: Previous meta-analyses have shown reduced risks of composite adverse events with intravascular imaging-guided percutaneous coronary intervention (PCI) compared with angiography guidance alone. However, these studies have been insufficiently powered to show whether all-cause death or all myocardial infarction are reduced with intravascular imaging guidance, and most previous intravascular imaging studies were done with intravascular ultrasound rather than optical coherence tomography (OCT), a newer imaging modality. We aimed to assess the comparative performance of intravascular imaging-guided PCI and angiography-guided PCI with drug-eluting stents. METHODS: For this systematic review and updated meta-analysis, we searched the MEDLINE, Embase, and Cochrane databases from inception to Aug 30, 2023, for studies that randomly assigned patients undergoing PCI with drug-eluting stents either to intravascular ultrasound or OCT, or both, or to angiography alone to guide the intervention. The searches were done and study-level data were extracted independently by two investigators. The primary endpoint was target lesion failure, defined as the composite of cardiac death, target vessel-myocardial infarction (TV-MI), or target lesion revascularisation, assessed in patients randomly assigned to intravascular imaging guidance (intravascular ultrasound or OCT) versus angiography guidance. We did a standard frequentist meta-analysis to generate direct data, and a network meta-analysis to generate indirect data and overall treatment effects. Outcomes were expressed as relative risks (RRs) with 95% CIs at the longest reported follow-up duration. This study was registered with the international prospective register of systematic reviews (PROSPERO, number CRD42023455662). FINDINGS: 22 trials were identified in which 15 964 patients were randomised and followed for a weighted mean duration of 24·7 months (longest duration of follow-up in each study ranging from 6 to 60 months). Compared with angiography-guided PCI, intravascular imaging-guided PCI resulted in a decreased risk of target lesion failure (RR 0·71 [95% CI 0·63-0·80]; p<0·0001), driven by reductions in the risks of cardiac death (RR 0·55 [95% CI 0·41-0·75]; p=0·0001), TV-MI (RR 0·82 [95% CI 0·68-0·98]; p=0·030), and target lesion revascularisation (RR 0·72 [95% CI 0·60-0·86]; p=0·0002). Intravascular imaging guidance also reduced the risks of stent thrombosis (RR 0·52 [95% CI 0·34-0·81]; p=0·0036), all myocardial infarction (RR 0·83 [95% CI 0·71-0·99]; p=0·033), and all-cause death (RR 0·75 [95% CI 0·60-0·93]; p=0·0091). Outcomes were similar for OCT-guided and intravascular ultrasound-guided PCI. INTERPRETATION: Compared with angiography guidance, intravascular imaging guidance of coronary stent implantation with OCT or intravascular ultrasound enhances both the safety and effectiveness of PCI, reducing the risks of death, myocardial infarction, repeat revascularisation, and stent thrombosis. FUNDING: Abbott.

Presence and Relevance of Myocardial Bridge in LAD-PCI of CTO and Non-CTO Lesions.

BACKGROUND: Intravascular ultrasound (IVUS) studies show that one-quarter of left anterior descending (LAD) arteries have a myocardial bridge. An MB may be associated with stent failure when the stent extends into the MB. OBJECTIVES: The aim of this study was to investigate: 1) the association between an MB and chronic total occlusion (CTO) in any LAD lesions; and 2) the association between an MB and subsequent clinical outcomes after percutaneous coronary intervention in LAD CTOs. METHODS: A total of 3,342 LAD lesions with IVUS-guided percutaneous coronary intervention (280 CTO and 3,062 non-CTO lesions) were included. The primary outcome was target lesion failure (cardiac death, target vessel myocardial infarction, definite stent thrombosis, and ischemic-driven target lesion revascularization). RESULTS: An MB by IVUS was significantly more prevalent in LAD CTOs than LAD non-CTOs (40.4% [113/280] vs 25.8% [789/3,062]; P < 0.0001). The discrepancy in CTO length between angiography and IVUS was greater in 113 LAD CTOs with an MB than 167 LAD CTOs without an MB (6.0 [Q1, Q3: 0.1, 12.2] mm vs 0.2 [Q1, Q3: -1.4, 8.4] mm; P < 0.0001). Overall, 48.7% (55/113) of LAD CTOs had a stent that extended into an MB after which target lesion failure was significantly higher compared to a stent that did not extend into an MB (26.3% vs 0%; P = 0.0004) or compared to an LAD CTO without an MB (26.3% vs 9.6%; P = 0.02). CONCLUSIONS: An MB was more common in LAD CTO than non-CTO LAD lesions. If present, approximately one-half of LAD CTOs had a stent extending into an MB that, in turn, was associated with worse outcomes.

Ostial right coronary artery lesion morphology and outcomes after treatment with drug-eluting stents.

BACKGROUND: Outcomes after percutaneous coronary intervention (PCI) for de novo ostial right coronary artery (RCA) lesions are poor. AIMS: We used intravascular ultrasound (IVUS) to clarify the morphological patterns of de novo ostial RCA lesions and their associated clinical outcome. METHODS: Among 5,102 RCA IVUS studies, 170 de novo ostial RCA stenoses (within 3 mm from the aorto-ostium) were identified. These were classified as 1) isolated ostial lesions (no disease extending beyond 10 mm from the ostium and without a calcified nodule [CN]); 2) ostial CN, typically with diffuse disease (disease extending beyond 10 mm); and 3) ostial lesions with diffuse disease but without a CN. The primary outcome was target lesion failure (TLF: cardiac death, target vessel myocardial infarction, definite stent thrombosis, and ischaemia-driven target lesion revascularisation). RESULTS: The prevalence of an isolated ostial lesion was 11.8% (n=20), 47.6% (n=81) were ostial CN, and 40.6% (n=69) were ostial lesions with diffuse disease. Compared to ostial lesions with diffuse disease, isolated lesions were more common in women (75.0% vs 42.0%; p=0.01), and CN were associated with older age (median [first, third quartile] 76 [70, 83] vs 69 [63, 81] years old; p=0.002). The Kaplan-Meier rate of TLF at 2 years was significantly higher in patients with CN (21.6%) compared to diffuse lesions (8.2%) (p=0.04), and patients with isolated lesions had no events. A multivariable Cox proportional hazard model revealed that CN were significantly associated with TLF (hazard ratio 6.63, 95% confidence interval: 1.28-34.3; p=0.02). CONCLUSIONS: Ostial RCA lesions have specific morphologies - detectable by IVUS - that may be associated with long-term clinical outcomes.

Intravascular Imaging-Guided Versus Angiography-Guided Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Trials.

BACKGROUND: Despite the initial evidence supporting the utility of intravascular imaging to guide percutaneous coronary intervention (PCI), adoption remains low. Recent new trial data have become available. An updated study-level meta-analysis comparing intravascular imaging to angiography to guide PCI was performed. This study aimed to evaluate the clinical outcomes of intravascular imaging-guided PCI compared with angiography-guided PCI. METHODS AND RESULTS: A random-effects meta-analysis was performed on the basis of the intention-to-treat principle. The primary outcomes were major adverse cardiac events, cardiac death, and all-cause death. Mixed-effects meta-regression was performed to investigate the impact of complex PCI on the primary outcomes. A total of 16 trials with 7814 patients were included. The weighted mean follow-up duration was 28.8 months. Intravascular imaging led to a lower risk of major adverse cardiac events (relative risk [RR], 0.67 [95% CI, 0.55-0.82]; P<0.001), cardiac death (RR, 0.49 [95% CI, 0.34-0.71]; P<0.001), stent thrombosis (RR, 0.63 [95% CI, 0.40-0.99]; P=0.046), target-lesion revascularization (RR, 0.67 [95% CI, 0.49-0.91]; P=0.01), and target-vessel revascularization (RR, 0.60 [95% CI, 0.45-0.80]; P<0.001). In complex lesion subsets, the point estimate for imaging-guided PCI compared with angiography-guided PCI for all-cause death was a RR of 0.75 (95% CI, 0.55-1.02; P=0.07). CONCLUSIONS: In patients undergoing PCI, intravascular imaging is associated with reductions in major adverse cardiac events, cardiac death, stent thrombosis, target-lesion revascularization, and target-vessel revascularization. The magnitude of benefit is large and consistent across all included studies. There may also be benefits in all-cause death, particularly in complex lesion subsets. These results support the use of intravascular imaging as standard of care and updates of clinical guidelines.

Rotational atherectomy combined with cutting balloon to optimise stent expansion in calcified lesions: the ROTA-CUT randomised trial.

BACKGROUND: Percutaneous coronary intervention (PCI) of calcified lesions remains challenging for interventionalists. AIMS: We aimed to investigate whether combining rotational atherectomy (RA) with cutting balloon angioplasty (RA+CBA) results in more optimal stent expansion compared with RA followed by non-compliant balloon angioplasty (RA+NCBA). METHODS: ROTA-CUT is a prospective, multicentre, randomised trial of 60 patients with coronary artery disease undergoing PCI of moderately or severely calcified lesions with drug-eluting stent implantation. Patients were randomised 1:1 to either RA+CBA or RA+NCBA. The primary endpoint was the minimum stent area on intravascular ultrasound (IVUS). Secondary endpoints included minimum lumen area and stent expansion assessed by IVUS and acute lumen gain, final residual diameter stenosis and minimum lumen diameter assessed by angiography. Clinical endpoints were obtained at 30 days. RESULTS: The mean age was 71.1±9.4 years, and 22% were women. The procedural details of RA were similar between groups, as were procedure duration and contrast use. Minimum stent area was similar with RA+CBA versus RA+NCBA (6.7±1.7 mm2 vs 6.9±1.8 mm2; p=0.685). Furthermore, there were no significant differences regarding the other IVUS and angiographic endpoints. Procedural complications were rare, and 30-day clinical events included 2 myocardial infarctions and 1 target vessel revascularisation in the RA+CBA group and 1 myocardial infarction in the RA+NCBA group. CONCLUSIONS: Combining RA with CBA resulted in a similar minimum stent area compared with RA followed by NCBA in patients undergoing PCI of moderately or severely calcified lesions. RA followed by CBA was safe with rare procedural complications and few clinical adverse events at 30 days.

Changes in post-PCI physiology based on anatomical vessel location: a DEFINE PCI substudy.

BACKGROUND: Anatomical vessel location affects post-percutaneous coronary intervention (PCI) physiology. AIMS: We aimed to compare the post-PCI instantaneous wave-free ratio (iFR) in left anterior descending (LAD) versus non-LAD vessels and to identify the factors associated with a suboptimal post-PCI iFR. METHODS: DEFINE PCI was a multicentre, prospective, observational study in which a blinded post-PCI iFR pullback was used to assess residual ischaemia following angiographically successful PCI. RESULTS: Pre- and post-PCI iFR recordings of 311 LAD and 195 non-LAD vessels were compared. Though pre-PCI iFR in the LAD vessels (median 0.82 [0.63, 0.86]) were higher compared with those in non-LAD vessels (median 0.72 [0.49, 0.84]; p<0.0001), post-PCI iFR were lower in the LAD vessels (median 0.92 [0.88, 0.94] vs 0.98 [0.95, 1.00]; p<0.0001). The prevalence of a suboptimal post-PCI iFR of <0.95 was higher in the LAD vessels (77.8% vs 22.6%; p<0.0001). While the overall frequency of residual physiological diffuse disease (31.4% vs 38.6%; p=0.26) and residual focal disease in the non-stented segment (49.6% vs 50.0%; p=0.99) were similar in both groups, residual focal disease within the stented segment was more common in LAD versus non-LAD vessels (53.7% vs 27.3%; p=0.0009). Improvement in iFR from pre- to post-PCI was associated with angina relief regardless of vessel location. CONCLUSIONS: After angiographically successful PCI, post-PCI iFR is lower in the LAD compared with non-LAD vessels, resulting in a higher prevalence of suboptimal post-PCI iFR in LAD vessels. This difference is, in part, due to a greater frequency of a residual focal pressure gradient within the stented segment which may be amenable to more aggressive PCI.