Prospective Deep Learning-based Quantitative Assessment of Coronary Plaque by CT Angiography Compared with Intravascular Ultrasound.

AIMS: Coronary computed tomography angiography provides noninvasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicenter international study compared an automated deep-learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). METHODS AND RESULTS: The study included clinically stable patients with known coronary artery disease from 15 centers in the U.S. and Japan. An artificial intelligence (AI)-enabled plaque analysis service was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm. Mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. CONCLUSIONS: Artificial intelligence enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.[ClinicalTrails.gov identifier: NCT05138289].

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.

1-Year Outcomes of Blinded Physiological Assessment of Residual Ischemia After Successful PCI: DEFINE PCI Trial.

OBJECTIVES: The aim of this study was to identify the post-percutaneous coronary intervention (PCI) target value of instantaneous wave-free ratio (iFR) that would best discriminate clinical events at 1 year in the DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) study. BACKGROUND: The impact of residual ischemia detected by iFR post-PCI on clinical and symptom-related outcomes is unknown. METHODS: Blinded iFR pull back was performed after successful stent implantation in 500 patients. The primary endpoint was the rate of residual ischemia, defined as iFR ≤0.89, after operator-assessed angiographically successful PCI. Secondary endpoints included clinical events at 1 year and change in Seattle Angina Questionnaire angina frequency (SAQ-AF) score during follow-up. RESULTS: As reported, 24.0% of patients had residual ischemia (iFR ≤0.89) after successful PCI, with 81.6% of cases attributable to angiographically inapparent focal lesions. Post-PCI iFR ≥0.95 (present in 182 cases [39%]) was associated with a significant reduction in the composite of cardiac death, spontaneous myocardial infarction, or clinically driven target vessel revascularization compared with post-PCI iFR <0.95 (1.8% vs 5.7%; P = 0.04). Baseline SAQ-AF score was 73.3 ± 22.8. For highly symptomatic patients (baseline SAQ-AF score ≤60), SAQ-AF score increased by ≥10 points more frequently in patients with versus without post-PCI iFR ≥0.95 (100.0% vs 88.5%; P = 0.01). CONCLUSIONS: In DEFINE PCI, despite angiographically successful PCI, highly symptomatic patients at baseline without residual ischemia by post-PCI iFR had greater reductions in anginal symptoms at 1 year compared with patients with residual ischemia. Achieving post-PCI iFR ≥0.95 was also associated with improved 1-year event-free survival. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367).

Clinical determinants of coronary artery disease burden and vulnerability using optical coherence tomography co-registered with intravascular ultrasound.

OBJECTIVES: We investigated clinical determinants of disease burden and vulnerability using optical coherence tomography (OCT) co-registered with intravascular ultrasound (IVUS) in a large cohort of patients. METHODS: A total of 704 patients [44.5% with acute coronary syndromes (ACS)] underwent coronary intervention. IVUS plaque burden and OCT lipid, macrophage and calcium indices and the presence of thrombus, plaque rupture and thin-cap fibroatheroma (TCFA) were analyzed. RESULTS: Median patient age was 66 years with 81.8% men, 34.4% with diabetes mellitus and 15.5% with preadmission statins. Median lesion length was 25.7 mm, and 33.0% had a TCFA. Adjusted models indicated (1) older patient age was related to more calcium, but fewer macrophages; (2) men were related to more thrombus with plaque rupture while women had more thrombus without plaque rupture; (3) ACS presentation was related to morphological acute thrombotic events (more thrombus with/without rupture) and plaque vulnerability (more TCFA, more lipid and macrophages and larger plaque burden); (4) diabetes mellitus was related to a greater atherosclerotic disease burden (more lipid and calcium and larger plaque burden) and more thrombus without rupture; (5) hypertension was related to more macrophages; (6) current smoking was related to less calcium; and (7) renal insufficiency and preadmission statin therapy were not independently associated with IVUS or OCT plaque morphology. CONCLUSION: Patient characteristics, especially diabetes mellitus and aging, affect underlying atherosclerotic burden, among which a greater lipidic burden along with sex differences influence local thrombotic morphology that affects clinical presentation.

Blinded Physiological Assessment of Residual Ischemia After Successful Angiographic Percutaneous Coronary Intervention: The DEFINE PCI Study.

OBJECTIVES: This study sought to evaluate the incidence and causes of an abnormal instantaneous wave-free ratio (iFR) after angiographically successful percutaneous coronary intervention (PCI). BACKGROUND: Impaired coronary physiology as assessed by fractional flow reserve is present in some patients after PCI and is prognostically relevant. METHODS: DEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) was a multicenter, prospective, observational study in which a blinded iFR pull back was performed after angiographically successful PCI in 562 vessels in 500 patients. Inclusion criteria were angina with either multivessel or multilesion coronary artery disease with an abnormal baseline iFR. The primary endpoint of the study was the rate of residual ischemia after operator-assessed angiographically successful PCI, defined as an iFR <0.90. The causes of impaired iFR were categorized as stent related, untreated proximal or distal focal stenosis, or diffuse atherosclerosis. RESULTS: An average of 1.1 vessels per patient had abnormal baseline iFRs, with a mean value of 0.69 ± 0.22, which improved to 0.93 ± 0.07 post-PCI. Residual ischemia after angiographically successful PCI was present in 112 patients (24.0%), with a mean iFR in that population of 0.84 ± 0.06 (range 0.60 to 0.89). Among patients with impaired post-PCI iFRs, 81.6% had untreated focal stenoses that were angiographically inapparent, and 18.4% had diffuse disease. Among the focal lesions, 38.4% were located within the stent segment, while 31.5% were proximal and 30.1% were distal to the stent. Post-PCI vessel angiographic diameter stenosis was not a predictor of impaired post-procedural iFR. CONCLUSIONS: Blinded post-PCI physiological assessment detected residual ischemia in nearly 1 in 4 patients after coronary stenting despite an operator-determined angiographically successful result. Most cases of residual ischemia were due to inapparent focal lesions potentially amenable to treatment with additional PCI. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367).

Intravascular Ultrasound Assessment of In-Stent Restenosis in Saphenous Vein Grafts.

Outcomes after percutaneous coronary interventions (PCI) in saphenous vein grafts (SVG) are inferior compared with native coronary arteries, but the mechanisms of SVG in-stent restenosis (ISR) have not been well-described. Thus, we aimed to evaluate the patterns of SVG ISR using intravascular ultrasound (IVUS) in 54 SVG ISR lesions. Stent underexpansion was defined as minimum stent area (MSA) <5 mm2. The time from stent implantation to presentation with ISR (9 BMS, 18 first-generation DES, and 27 second-generation DES) was 3.7 ± 3.0 years. IVUS-defined ISR patterns were categorized as mechanical (33%) or biological (67%). Mechanical patterns comprised 10 cases of stent underexpansion (MSA = 4.2 ± 0.9 mm2), 6 stent fractures or deformations, and 2 uncovered aorto-anastomotic lesions. Biological patterns comprised 19 cases of neoatherosclerosis, 13 excessive neointimal hyperplasia (NIH, 65 ± 11%), and 4 thrombi. Compared with biological patterns of ISR, mechanical patterns were more frequently located at the SVG anastomosis (72% vs 39%, p = 0.04) and at the SVG hinge motion site (55% vs 21%, p = 0.02). Although patients with mechanical patterns of ISR presented earlier than those with biological patterns (2.3 vs 4.4 years, p = 0.009), 61% of them were diagnosed >1 year after stent implantation. In conclusion, SVG ISR is dominated by biological patterns including neoatherosclerosis. Mechanical patterns of SVG ISR are associated with earlier presentation and location at graft anastomosis or hinge motion site.

Optical Coherence Tomography Assessment of Morphological Characteristics in Suspected Coronary Artery Disease, but Angiographically Nonobstructive Lesions.

BACKGROUND/PURPOSE: We sought to evaluate the morphological characteristics of nonobstructive coronary lesions in patients with ischemic symptoms and/or signs. MATERIALS/METHODS: We used optical coherence tomography (OCT) to assess the presumed culprit lesion in 142 patients with suspected coronary artery disease in whom coronary angiography showed no lesion with a diameter stenosis ≥50%. Patients with a clinical diagnosis of acute coronary syndrome (ACS, n = 31, including 2 ST-elevation myocardial infarction, 9 non-ST-elevation myocardial infarction, and 20 unstable angina pectoris) were compared to those with stable coronary artery disease (CAD) (n = 111) including 79 patients with stable angina and 32 patients with silent ischemia (positive non-invasive stress test only). RESULTS: The overall prevalence of thrombus, plaque rupture, intimal laceration, or calcified nodule in the combined groups was 23.2% (33/142) including 15 thrombus, 12 plaque rupture, 9 calcified nodule, and 8 intimal laceration (not mutually exclusive) without differences between ACS and stable CAD patients. Also the prevalence of thin-cap fibroatheroma was not significantly different between ACS and stable patients (12.9% vs 6.3%, p = 0.22). Minimum lumen area (3.1 mm2 [2.3, 4.1] versus 3.2 mm2 [2.4, 4.7], p = 0.7) and area stenosis (49.9% [37.1, 56.4] versus 48.1% [37.8, 55.8], p = 0.9) were similar between ACS and stable CAD patients. CONCLUSION: In patients presenting with ischemic symptoms and/or signs, but angiographically nonobstructive culprit lesions, approximately 25% had abnormal findings by OCT-whether patients presented with acute/unstable or stable CAD.

Predictors and Long-Term Clinical Impact of Acute Stent Malapposition: An Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents (ADAPT-DES) Intravascular Ultrasound Substudy.

BACKGROUND: The impact of acute stent malapposition (ASM) on long-term clinical outcomes in patients undergoing percutaneous coronary intervention is still controversial. We sought to evaluate predictors and long-term clinical outcomes of ASM. METHODS AND RESULTS: ADAPT-DES (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) was a prospective multicenter study of 8663 patients undergoing percutaneous coronary intervention using drug-eluting stents. In a prespecified intravascular ultrasound-guided substudy, 2072 patients with 2446 culprit lesions had post-percutaneous coronary intervention intravascular ultrasound and were classified according to the presence or absence of ASM. After intravascular ultrasound-guided percutaneous coronary intervention, the overall prevalence of ASM after successful drug-eluting stents implantation was 14.4% per patient and 12.6% per lesion. Compared to lesions without ASM, lesions with ASM had larger in-stent lumen areas, larger stent areas, and larger in-stent vessel areas. A larger mean plaque area along with more attenuated plaque was observed in lesions with ASM versus lesions without ASM. Lesions with ASM had greater proximal and distal reference lumen areas and more distal, but not proximal, reference calcium compared to lesions without ASM. At 2-year follow-up, there was no significant difference in the incidence of cardiac death; myocardial infarction; early, late, or very late stent thrombosis; or clinically driven target lesion revascularization in patients with ASM versus those without ASM. Furthermore, ASM was not an independent predictor of 2-year major adverse cardiac events or target lesion revascularization even when forced into the multivariate model. CONCLUSIONS: In patients treated with intravascular ultrasound-guided drug-eluting stents implantation, ASM was not associated with adverse clinical events during long-term follow-up including, but not limited to, stent thrombosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00638794.

Continuum of Vasodilator Stress From Rest to Contrast Medium to Adenosine Hyperemia for Fractional Flow Reserve Assessment.

OBJECTIVES: This study compared the diagnostic performance with adenosine-derived fractional flow reserve (FFR) ≤0.8 of contrast-based FFR (cFFR), resting distal pressure (Pd)/aortic pressure (Pa), and the instantaneous wave-free ratio (iFR). BACKGROUND: FFR objectively identifies lesions that benefit from medical therapy versus revascularization. However, FFR requires maximal vasodilation, usually achieved with adenosine. Radiographic contrast injection causes submaximal coronary hyperemia. Therefore, intracoronary contrast could provide an easy and inexpensive tool for predicting FFR. METHODS: We recruited patients undergoing routine FFR assessment and made paired, repeated measurements of all physiology metrics (Pd/Pa, iFR, cFFR, and FFR). Contrast medium and dose were per local practice, as was the dose of intracoronary adenosine. Operators were encouraged to perform both intracoronary and intravenous adenosine assessments and a final drift check to assess wire calibration. A central core lab analyzed blinded pressure tracings in a standardized fashion. RESULTS: A total of 763 subjects were enrolled from 12 international centers. Contrast volume was 8 ± 2 ml per measurement, and 8 different contrast media were used. Repeated measurements of each metric showed a bias <0.005, but a lower SD (less variability) for cFFR than resting indexes. Although Pd/Pa and iFR demonstrated equivalent performance against FFR ≤0.8 (78.5% vs. 79.9% accuracy; p = 0.78; area under the receiver-operating characteristic curve: 0.875 vs. 0.881; p = 0.35), cFFR improved both metrics (85.8% accuracy and 0.930 area; p < 0.001 for each) with an optimal binary threshold of 0.83. A hybrid decision-making strategy using cFFR required adenosine less often than when based on either Pd/Pa or iFR. CONCLUSIONS: cFFR provides diagnostic performance superior to that of Pd/Pa or iFR for predicting FFR. For clinical scenarios or health care systems in which adenosine is contraindicated or prohibitively expensive, cFFR offers a universal technique to simplify invasive coronary physiological assessments. Yet FFR remains the reference standard for diagnostic certainty as even cFFR reached only ∼85% agreement.

Assessment and Quantitation of Stent Results by Intracoronary Optical Coherence Tomography.

Optical coherence tomography evaluation of poststent results includes stent expansion as the absolute minimum stent area ratio by comparing the minimum stent area with the proximal and distal reference lumen areas or mean stent area defined as the total stent volume divided by the analyzed stent length; stent strut malapposition defined when the distance from the center of the blooming artifact and the surface of plaque is greater than the sum of stent thickness and polymer thickness; tissue protrusion through the stent struts; semiquantitative residual thrombus evaluation; and stent edge dissection.