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.

Ticagrelor with or without aspirin following percutaneous coronary intervention in high-risk patients with concomitant peripheral artery disease: A subgroup analysis of the TWILIGHT randomized clinical trial.

BACKGROUND: The optimal antiplatelet regimen after percutaneous coronary intervention (PCI) in patients with peripheral artery disease (PAD) is still debated. This analysis aimed to compare the effect of ticagrelor monotherapy versus ticagrelor plus aspirin in patients with PAD undergoing PCI. METHODS: In the TWILIGHT trial, patients at high ischemic or bleeding risk that underwent PCI were randomized after 3 months of dual antiplatelet therapy (DAPT) to aspirin or matching placebo in addition to open-label ticagrelor for 12 additional months. In this post-hoc analysis, patient cohorts were examined according to the presence or absence of PAD. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction (MI), or stroke. Endpoints were assessed at 12 months after randomization. RESULTS: Among 7,119 patients, 489 (7%) had PAD and were older, more likely to have comorbidities, and multivessel disease. PAD patients had more bleeding or ischemic complications than no-PAD patients. Ticagrelor monotherapy compared to ticagrelor plus aspirin was associated with less BARC 2, 3, or 5 bleeding in PAD (4.6% vs 8.7%; HR 0.52; 95%CI 0.25-1.07) and no-PAD patients (4.0% vs 7.0%; HR 0.56; 95%CI 0.45-0.69; interaction P-value .830) and a similar risk of death, MI, or stroke in these 2 groups (interaction P-value .446). CONCLUSIONS: Despite their higher ischemic and bleeding risk, patients with PAD undergoing PCI derived a consistent benefit from ticagrelor monotherapy after 3 months of DAPT in terms of bleeding reduction without any relevant increase in ischemic events. CLINICAL TRIAL REGISTRY INFORMATION:: https://www. CLINICALTRIALS: gov/study/NCT02270242.

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.

Impact of Calcium Eccentricity on the Safety and Effectiveness of Coronary Intravascular Lithotripsy: Pooled Analysis From the Disrupt CAD Studies.

BACKGROUND: Coronary intravascular lithotripsy (IVL) safely facilitates successful stent implantation in severely calcified lesions. This analysis sought to determine the relative impact of lesion calcium eccentricity on the safety and effectiveness of IVL using high-resolution optical coherence tomography imaging. METHODS: Individual patient-level data (n=262) were pooled from 4 distinct international prospective studies (Disrupt CAD I, II, III, and IV) and analyzed by an independent optical coherence tomography core laboratory. IVL performance in eccentric versus concentric calcification was analyzed by dividing calcified lesions into quartiles (≤180° [most eccentric], 181°-270°, 271°-359°, and 360° [concentric]) by maximum continuous calcium arc. RESULTS: In the 230 patients with clear imaging field on optical coherence tomography, there were no differences in preprocedure minimum lumen area, diameter stenosis, or maximum calcium thickness. The calcium length and volume index increased progressively with increasing mean and maximum continuous calcium arc (ie, concentricity). Conversely, the minimum calcium thickness decreased progressively with increasing concentricity. Post-procedure, the number of calcium fractures, fracture depth, and fracture width increased with increasing concentricity, with a 4-fold increase in the number of fractures in lesions with 360° of calcium arc compared with ≤180°. This increase in IVL-induced calcium fracture with increasing calcium burden and concentricity facilitated stent expansion and luminal gain such that there were no significant differences across quartiles. CONCLUSIONS: IVL induced calcium fractures proportional to the magnitude of coronary artery calcium, including in eccentric calcium, leading to consistent improvements in stent expansion and luminal gain in both eccentric and concentric calcified coronary lesions.

Clinically Driven Revascularization in High-Risk Patients Treated With Ticagrelor Monotherapy After PCI: Insights from the Randomized TWILIGHT Trial.

Repeat coronary revascularization is a common adverse event after successful percutaneous coronary intervention. This analysis aimed to assess the effects of ticagrelor monotherapy on repeat clinically driven revascularization (CDR). In the TWILIGHT (Ticagrelor With Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomly allocated to aspirin or placebo for 1 year. The primary end point of this analysis was CDR within 12 months after randomization. The key secondary end points were major adverse cardiovascular and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, stroke, or CDR, and net adverse clinical events (NACEs), including the individual components of MACCEs and clinically relevant bleeding. The analysis was performed in the per-protocol population. CDR occurred in 473 of 7,039 patients and was associated with a significantly higher risk of subsequent all-cause death, myocardial infarction, or stroke (adjusted hazard ratios [HRs] 2.92, 95% confidence interval [CI] 1.82 to 4.67). Ticagrelor monotherapy was associated with a similar 12-month risk of CDR (7.1% vs 6.6%; HR 1.09, 95% CI 0.90 to 1.30, p = 0.363) and MACCEs (8.9% vs 8.6%; HR 1.04, 95% CI 0.89 to 1.22, p = 0.619), and a lower risk of NACEs (12.2% vs 14.6%; HR 0.83 95% CI 0.73 to 0.94, p = 0.004) than ticagrelor plus aspirin. In conclusion, among high-risk patients who underwent percutaneous coronary intervention, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a similar risk of CDR and MACCEs and a decrease of NACEs (TWILIGHT: NCT02270242).

Optical Coherence Tomography-Guided versus Angiography-Guided PCI.

BACKGROUND: Data regarding clinical outcomes after optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) as compared with angiography-guided PCI are limited. METHODS: In this prospective, randomized, single-blind trial, we randomly assigned patients with medication-treated diabetes or complex coronary-artery lesions to undergo OCT-guided PCI or angiography-guided PCI. A final blinded OCT procedure was performed in patients in the angiography group. The two primary efficacy end points were the minimum stent area after PCI as assessed with OCT and target-vessel failure at 2 years, defined as a composite of death from cardiac causes, target-vessel myocardial infarction, or ischemia-driven target-vessel revascularization. Safety was also assessed. RESULTS: The trial was conducted at 80 sites in 18 countries. A total of 2487 patients underwent randomization: 1233 patients were assigned to undergo OCT-guided PCI, and 1254 to undergo angiography-guided PCI. The minimum stent area after PCI was 5.72±2.04 mm2 in the OCT group and 5.36±1.87 mm2 in the angiography group (mean difference, 0.36 mm2; 95% confidence interval [CI], 0.21 to 0.51; P<0.001). Target-vessel failure within 2 years occurred in 88 patients in the OCT group and in 99 patients in the angiography group (Kaplan-Meier estimates, 7.4% and 8.2%, respectively; hazard ratio, 0.90; 95% CI, 0.67 to 1.19; P = 0.45). OCT-related adverse events occurred in 1 patient in the OCT group and in 2 patients in the angiography group. Stent thrombosis within 2 years occurred in 6 patients (0.5%) in the OCT group and in 17 patients (1.4%) in the angiography group. CONCLUSIONS: Among patients undergoing PCI, OCT guidance resulted in a larger minimum stent area than angiography guidance, but there was no apparent between-group difference in the percentage of patients with target-vessel failure at 2 years. (Funded by Abbott; ILUMIEN IV: OPTIMAL PCI ClinicalTrials.gov number, NCT03507777.).

Impact of Eruptive vs Noneruptive Calcified Nodule Morphology on Acute and Long-Term Outcomes After Stenting.

BACKGROUND: Whether an eruptive or noneruptive target lesion calcified nodule (CN) portends worse acute and long-term clinical outcomes after stenting has not been established. OBJECTIVES: The authors sought to compare acute and long-term clinical outcomes in eruptive CN vs noneruptive CN morphology. METHODS: Using optical coherence tomography, an eruptive CN was defined as an accumulation of small calcium fragments protruding and disrupting the overlying fibrous cap, typically with small amount of thrombus. A noneruptive CN was defined as an accumulation of small calcium fragments with a smooth intact fibrous cap without an overlying thrombus. The primary endpoint was target lesion failure (TLF) including cardiac death, target vessel myocardial infarction, or clinically driven target lesion revascularization in patients with ≥6-month follow-up. RESULTS: Among 3,231 patients with evaluable pre- and postintervention OCT, 236 patients had lesions with CNs (7.3%). After eliminating 4 secondary lesions and 6 patients without ≥6-month follow-up, 126 (54.8%) lesions with eruptive CNs and 104 (45.2%) lesions with noneruptive CNs formed the current report. Compared with noneruptive CNs, eruptive CNs were independently associated with greater stent expansion (89.2% ± 18.7% vs. 81.5% ± 18.9%; P = 0.003) after adjusting for morphologic and procedural factors. At 2 years, eruptive CNs trended toward more TLF compared with noneruptive CNs (Kaplan-Meier estimates, 19.8% vs 12.5%; P = 0.11) and significantly more target lesion revascularization (18.3% vs 9.6%; P = 0.04). In the adjusted model, eruptive CNs were independently associated with 2-year TLF (HR: 2.07; 95% CI: 1.01-4.50; P = 0.048). CONCLUSIONS: Compared with noneruptive CN morphology, lesions with an eruptive CN appearance on optical coherence tomography had a worse poststent long-term clinical outcome despite better acute stent expansion.

Optical Coherence Tomography-Guided Percutaneous Coronary Intervention: Practical Application.

Optical coherence tomography (OCT) provides high-resolution imaging of coronary arteries and can be used to optimize percutaneous coronary intervention (PCI). Intracoronary OCT, however, has had limited adoption in clinical practice. Novelty and relative complexity of OCT interpretation compared with the more established intravascular ultrasound, lack of a standardized algorithm for PCI guidance, paucity of data from randomized trials, and lack of rebate for intravascular imaging have contributed to the modest practical adoption of OCT. We provide a practical step-by-step guide on how to use OCT in PCI, including device set-up, simplified image interpretation, and an algorithmic approach for PCI. optimization.

Ticagrelor with or without aspirin in high-risk patients with anaemia undergoing percutaneous coronary intervention: a subgroup analysis of the TWILIGHT trial.

AIM: The aim of this study was to assess the effect of ticagrelor monotherapy among high-risk patients with anaemia undergoing percutaneous coronary intervention (PCI). METHODS AND RESULTS: In the TWILIGHT (Ticagrelor with Aspirin or Alone in High-Risk Patients after Coronary Intervention) trial, after 3 months of ticagrelor plus aspirin, high-risk patients were maintained on ticagrelor and randomized to aspirin or placebo for 1 year. Anaemia was defined as haemoglobin <13 g/dL for men and <12 g/dL for women. The primary endpoint was Bleeding Academic Research Consortium (BARC) 2, 3, or 5 bleeding. The key secondary endpoint was a composite of all-cause death, myocardial infarction, or stroke.Out of 6828 patients, 1329 (19.5%) had anaemia and were more likely to have comorbidities, multivessel disease, and to experience bleeding or ischaemic complications than non-anaemic patients. Among anaemic patients, BARC 2, 3, or 5 bleeding occurred less frequently with ticagrelor monotherapy than with ticagrelor plus aspirin [6.4% vs. 10.7%; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41-0.88; P = 0.009]; the rate of the key secondary endpoint was similar in the two arms (5.2% vs. 4.8%; HR 1.07; 95% CI 0.66-1.74; P = 0.779). These effects were consistent in patients without anaemia (interaction P values 0.671 and 0.835, respectively). CONCLUSION: In high-risk patients undergoing PCI, ticagrelor monotherapy after 3 months of ticagrelor-based dual antiplatelet therapy was associated with a reduced risk of clinically relevant bleeding without any increase in ischaemic events irrespective of anaemia status (TWILIGHT: NCT02270242).

Visualizing Inside Conduits-Intraoperative Screening of Grafts by Optical Coherence Tomography.

PURPOSE: Saphenous vein graft (SVG) failure is a complex phenomenon, with technical, biologic, and local factors contributing to early and medium- and long-term failure after coronary artery bypass graft. Both technical and conduit factors may have significant impact on early SVG failure. DESCRIPTION: We review the complex factors that play a pathogenic role in SVG failure, followed by review of the existing literature on potential utility of high-definition optical coherence tomography (OCT) in comprehensive intraoperative assessment of SVGs. EVALUATION: We describe a new technique for intraoperative acquisition of OCT images in the harvested SVGs and introduce a classification system for pathologic processes that can be detected in the harvested SVG conduits by OCT. CONCLUSIONS: The potential impact on early graft failure of the exclusion of segments of SVGs that are less than optimal (ie, containing fibroatheroma, retained thrombus, sclerotic valves, or procurement injury) will be examined in the randomized controlled OCTOCAB (Intraoperative Optical Coherence Tomography of the Saphenous Vein Conduit in Patients Undergoing Coronary Artery Bypass Surgery) trial.

Optical coherence tomography versus angiography and intravascular ultrasound to guide coronary stent implantation: A systematic review and meta-analysis.

BACKGROUND: Optical coherence tomography (OCT) is an adjunct to angiography-guided coronary stent placement. However, in the absence of dedicated, appropriately powered randomized controlled trials, the impact of OCT on clinical outcomes is unclear. OBJECTIVE: To conduct a systematic review and meta-analysis of all available studies comparing OCT-guided versus angiography-guided and intravascular ultrasound (IVUS)-guided coronary stent implantation. METHODS: MEDLINE and Cochrane Central were queried from their inception through July 2022 for all studies that sought to compare OCT-guided percutaneous coronary intervention (PCI) to angiography-guided and IVUS-guided PCI. The primary endpoint was minimal stent area (MSA) compared between modalities. Clinical endpoints of interest were all-cause and cardiovascular mortality, major adverse cardiovascular events (MACE), myocardial infarction (MI), target lesion revascularization (TLR), target vessel revascularization (TVR), and stent thrombosis (ST). Risk ratios (RRs) and mean differences (MDs) with their corresponding 95% confidence intervals (CIs) were pooled using a random-effects model. RESULTS: Thirteen studies (8 randomized control trials and 5 observational studies) enrolling 6312 participants were included. OCT was associated with a strong trend toward increased MSA compared to angiography (MD = 0.36, p = 0.06). OCT-guided PCI was also associated with a reduction in the incidence of all-cause mortality [RR = 0.59, 95% CI (0.35, 0.97), p = 0.04] and cardiovascular mortality [RR = 0.41, 95% CI (0.21, 0.80), p = 0.009] compared with angiography-guided PCI. Point estimates favored OCT relative to angiography in MACE [RR = 0.75, 95% CI (0.47, 1.20), p = 0.22] and MI [RR = 0.75, 95% CI (0.53, 1.07), p = 0.12]. No differences were detected in ST [RR = 0.71, 95% CI (0.21, 2.44), p = 0.58], TLR [RR = 0.71, 95% CI (0.17, 3.05), p = 0.65], or TVR rates [RR = 0.89, 95% CI (0.46, 1.73), p = 0.73]. Compared with IVUS guidance, OCT guidance was associated with a nonsignificant reduction in the MSA (MD = -0.16, p = 0.27). The rates of all-cause and cardiovascular mortality, MACE, MI, TLR, TVR, or ST were similar between OCT-guided and IVUS-guided PCI. CONCLUSIONS: OCT-guided PCI was associated with reduced all-cause and cardiovascular mortality compared to angiography-guided PCI. These results should be considered hypothesis generating as the mechanisms for the improved outcomes were unclear as no differences were detected in the rates of TLR, TVR, or ST. OCT- and IVUS-guided PCI resulted in similar post-PCI outcomes.

Calcium Modification in Percutaneous Coronary Interventions.

Moderate-severe calcification increases procedural complications and impairs long-term prognosis post-PCI. Intravascular imaging (particularly optical coherence tomography [OCT]) is useful in guiding the treatment of calcified lesions. Weighted sum of calcium length, arc, and thickness on OCT can predict adequate stent expansion, identifying when atherectomy is required. With intravascular imaging guidance, various techniques alone or in combination may be used in an algorithmic fashion to modify calcified lesions. Calcium fracture by balloon angioplasty, cutting/scoring balloons, intravascular lithotripsy (IVL), atherectomy devices, or Excimer laser improves stent expansion. Intravascular imaging is essential in the treatment of in-stent restenosis when luminal and/or abluminal peri-strut calcium is present.

Intravascular Lithotripsy for Treatment of Calcified Coronary Artery Disease.

Intravascular lithotripsy (IVL) uses acoustic shock waves in a balloon-based delivery system to modify severely calcified atherosclerotic coronary vascular lesions in preparation for stent implantation. IVL results in circumferential and longitudinal calcium fracture, which improves transmural vessel compliance and facilitates subsequent stent expansion without requiring high-pressure balloon dilation. Clinical trials have demonstrated IVL to be safe (low rates of major adverse cardiac events in hospital and to 1 year; low rates of severe angiographic complications), effective (high rates of procedural success), and easy to use (little or no learning curve) when applied in the treatment of severely calcified coronary arteries.

Prevalence and Impact of Neoatherosclerosis on Clinical Outcomes After Percutaneous Treatment of Second-Generation Drug-Eluting Stent Restenosis.

BACKGROUND: Clinical and morphological factors associated with lipidic versus calcified neoatherosclerosis within second-generation drug-eluting stents and the impact of lipidic versus calcified neoatherosclerosis on long-term outcomes after repeat intervention have not been well studied. METHODS: A total of 512 patients undergoing optical coherence tomography before percutaneous coronary intervention for second-generation drug-eluting stents in-stent restenosis were included. Neoatherosclerosis was defined as lipidic or calcified neointimal hyperplasia in ≥3 consecutive frames or ruptured lipidic neointimal hyperplasia. The primary outcome was target lesion failure (cardiac death, target vessel myocardial infarction, definite stent thrombosis, or clinically driven target lesion revascularization). RESULTS: The overall prevalence of neoatherosclerosis was 28.5% (146/512): 56.8% lipidic, 30.8% calcified, and 12.3% both lipidic and calcific. The prevalence increased as a function of time from stent implantation: 20% at 1 to 3 years, 30% at 3 to 7 years, and 75% >7 years. Renal insufficiency, poor lipid profile, and time from stent implantation were associated with lipidic neoatherosclerosis, whereas severe renal insufficiency, female sex, and time from stent implantation were associated with calcified neoatherosclerosis. Multivariable Cox regression revealed that female sex and lipidic neoatherosclerosis were associated with more target lesion failure, whereas stent age and final minimum lumen diameter after reintervention were related to lower target lesion failure. Calcified neoatherosclerosis was not related to adverse events after reintervention for in-stent restenosis given a large enough minimum lumen diameter was achieved. CONCLUSIONS: Lipidic but not calcified neoatherosclerosis was associated with poor subsequent outcomes after repeat revascularization if optimal stent expansion was achieved in lesions with calcified neoatherosclerosis.