Validation of virtual fractional flow reserve pullback curves.

BACKGROUND: Angiography-derived fractional flow reserve (virtual FFR) has shown excellent diagnostic performance compared with wire-based FFR. However, virtual FFR pullback curves have not been validated yet. OBJECTIVES: To validate the accuracy of virtual FFR pullback curves compared to wire-based FFR pullbacks and to assess their clinical utility using patient-reported outcomes. METHODS: Pooled analysis of two prospective studies, including patients with hemodynamically significant (FFR ≤ 0.80) coronary artery disease (CAD). Virtual and wire-based FFR pullbacks were compared to assess the accuracy of virtual pullbacks to characterize CAD as focal or diffuse. Pullbacks were analyzed visually and quantitatively using the pullback pressure gradient (PPG). Patients underwent PCI, and the Seattle Angina Questionnaire (SAQ) was administered at 3-month follow-up. RESULTS: A total of 298 patients (300 vessels) with both virtual and wire-based pullbacks who underwent PCI were included in the analysis. The mean age was 61.8 ± 8.8, and 15% were female. The agreement on the visual adjudication of the CAD pattern was fair (Cohen's Kappa: 0.31, 95% confidence interval: 0.18-0.45). The mean PPG were 0.65 ± 0.18 from virtual pullbacks and 0.65 ± 0.13 from wire-based pullbacks (r = 0.68, mean difference 0, limits of agreement -0.27 to 0.28). At follow-up, patients with high virtual PPG (>0.67) had higher SAQ angina frequency scores (i.e., less angina) than those with low virtual PPG (SAQ scores 92.0 ± 14.3 vs. 85.5 ± 23.1, p = 0.022). CONCLUSION: Virtual FFR pullback curves showed moderate agreement with wire-based FFR pullbacks. Nonetheless, patients with focal disease based on virtual PPG reported greater improvement in angina after PCI.

Optical frequency domain imaging-guided versus intravascular ultrasound-guided percutaneous coronary intervention for acute coronary syndromes: the OPINION ACS randomised trial.

BACKGROUND: The clinical benefits of optical frequency domain imaging (OFDI)-guided percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remain unclear. AIMS: We sought to compare intravascular ultrasound (IVUS)- and OFDI-guided PCI in patients with ACS. METHODS: OPINION ACS is a multicentre, prospective, randomised, non-inferiority trial that compared OFDI-guided PCI with IVUS-guided PCI using current-generation drug-eluting stents in ACS patients (n=158). The primary endpoint was in-stent minimum lumen area (MLA), assessed using 8-month follow-up OFDI. RESULTS: Patients presented with ST-segment elevation myocardial infarction (55%), non-ST-segment elevation myocardial infarction (29%), or unstable angina pectoris (16%). PCI procedural success was achieved in all patients, with comparably low periprocedural complications rates in both groups. Immediately after PCI, the minimum stent area (p=0.096) tended to be smaller for OFDI versus IVUS guidance. Proximal stent edge dissection (p=0.012) and irregular protrusion (p=0.03) were significantly less frequent in OFDI-guided procedures than in IVUS-guided procedures. Post-PCI coronary flow, assessed using corrected Thrombolysis in Myocardial Infarction frame counts, was significantly better in the OFDI-guided group than in the IVUS-guided group (p<0.001). The least squares mean (95% confidence interval [CI]) in-stent MLA at 8 months was 4.91 (95% CI: 4.53-5.30) mm2 and 4.76 (95% CI: 4.35-5.17) mm2 in the OFDI- and IVUS-guided groups, respectively, demonstrating the non-inferiority of OFDI guidance (pnon-inferiority<0.001). The average neointima area tended to be smaller in the OFDI-guided group. The frequency of major adverse cardiac events was similar. CONCLUSIONS: Among ACS patients, OFDI-guided PCI and IVUS-guided PCI were equally safe and feasible, with comparable in-stent MLA at 8 months. OFDI guidance may be a potential option in ACS patients. This study was registered in the Japan Registry of Clinical Trials (jrct.niph.go.jp: jRCTs052190093).

Enhanced Plaque Stabilization Effects of Alirocumab　- Insights From Artificial Intelligence-Aided Optical Coherence Tomography Analysis of the Alirocumab for Thin-Cap Fibroatheroma in Patients With Coronary Artery Disease Estimated by Optical Coherence Tomography (ALTAIR) Study.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 inhibitors stabilize vulnerable plaque, reducing cardiovascular events. However, manual optical coherence tomography (OCT) analysis of drug efficacy is challenging because of signal attenuation within lipid plaques. METHODS AND RESULTS: Twenty-four patients with thin-cap fibroatheroma were prospectively enrolled and randomized to receive alirocumab (75 mg every 2 weeks) plus rosuvastatin (10 mg/day) or rosuvastatin (10 mg/day) alone. OCT images at baseline and 36 weeks were analyzed manually and with artificial intelligence (AI)-aided software. AI-aided OCT analysis showed significantly greater percentage changes in the alirocumab+rosuvastatin vs. rosuvastatin-alone group in fibrous cap thickness (FCT; median [interquartile range] 212.3% [140.5-253.5%] vs. 88.6% [63.0-119.6%]; P=0.006) and lipid volume (median [interquartile range] -30.8% [-51.8%, -16.6%] vs. -2.1% [-21.6%, 4.3%]; P=0.015). Interobserver reproducibility for changes in minimum FCT and lipid index was relatively low for manual analysis (interobserver intraclass correlation coefficient [ICC] 0.780 and 0.499, respectively), but high for AI-aided analysis (interobserver ICC 0.999 and 1.000, respectively). Agreements between manual and AI-aided OCT analyses of FCT and the lipid index were acceptable (concordance correlation coefficients 0.859 and 0.833, respectively). CONCLUSIONS: AI-aided OCT analysis objectively showed greater plaque stabilization of adding alirocumab to rosuvastatin. Our results highlight the benefits of a fully automated AI-assisted approach for assessing drug efficacy, offering greater objectivity in evaluating serial changes in plaque stability vs. conventional OCT assessment.

Predictors for Vulnerable Plaque in Functionally Significant Lesions.

BACKGROUND: Vulnerable plaque presents prognostic implications in addition to functional significance. OBJECTIVES: The aim of this study was to identify relevant features of vulnerable plaque in functionally significant lesions. METHODS: In this multicenter, prospective study conducted across 5 countries, including patients who had invasive fractional flow reserve (FFR) ≤0.80, a total of 95 patients with available pullback pressure gradient (PPG) and plaque analysis on coronary computed tomographic angiography and optical coherence tomography were analyzed. Vulnerable plaque was defined as the presence of plaque rupture or thin-cap fibroatheroma on optical coherence tomography. Among the 25 clinical characteristics, invasive angiographic findings, physiological indexes, and coronary computed tomographic angiographic findings, significant predictors of vulnerable plaque were identified. RESULTS: Mean percentage diameter stenosis, FFR, and PPG were 77.8% ± 14.6%, 0.66 ± 0.13, and 0.65 ± 0.13, respectively. Vulnerable plaque was present in 53 lesions (55.8%). PPG and FFR were identified as significant predictors of vulnerable plaque (P < 0.05 for all). PPG >0.65 and FFR ≤0.70 were significantly related to a higher probability of vulnerable plaque after adjustment for each other (OR: 6.75 [95% CI: 2.39-19.1]; P < 0.001] for PPG >0.65; OR: 4.61 [95% CI: 1.66-12.8]; P = 0.003 for FFR ≤0.70). When categorizing lesions according to combined PPG >0.65 and FFR ≤0.70, the prevalence of vulnerable plaque was 20.0%, 57.1%, 66.7%, and 88.2% in the order of PPG ≤0.65 and FFR >0.70, PPG ≤0.65 and FFR ≤0.70, PPG >0.65 and FFR >0.70, and PPG >0.65 and FFR ≤0.70 (P for trend < 0.001), respectively. CONCLUSIONS: Among low-FFR lesions, the presence of vulnerable plaque can be predicted by PPG combined with FFR without additional anatomical or plaque characteristics. (Precise Percutaneous Coronary Intervention Plan [P3] Study; NCT03782688).

Relationship Between Calcified Plaque Burden, Vascular Inflammation, and Plaque Vulnerability in Patients With Coronary Atherosclerosis.

BACKGROUND: Coronary artery calcification is an integral part of atherosclerosis. It has been suggested that early coronary artery calcification is associated with active inflammation, and advanced calcification forms as inflammation subsides. Inflammation is also an important factor in plaque vulnerability. However, the relationship between coronary artery calcium burden, vascular inflammation, and plaque vulnerability has not been fully investigated. OBJECTIVES: This study aimed to correlate calcified plaque burden (CPB) at the culprit lesion with vascular inflammation and plaque vulnerability. METHODS: Patients with coronary artery disease who had both computed tomography angiography and optical coherence tomography were included. The authors divided the patients into 4 groups: 1 group without calcification at the culprit lesion; and 3 groups based on the CPB tertiles. CPB was calculated as calcified plaque volume divided by vessel volume in the culprit lesion. The authors compared pericoronary adipose tissue (PCAT) attenuation for vascular inflammation and optical coherence tomography-derived vulnerable features among the 4 groups. RESULTS: Among 578 patients, the highest CPB tertile showed significantly lower PCAT attenuation of culprit vessel compared with the other groups. The prevalence of features of plaque vulnerability (including lipid-rich plaque, macrophage, and microvessel) was also lowest in the highest CPB tertile. In the patients with calcification, higher age, statin use, and lower PCAT attenuation were independently associated with CPB. CONCLUSIONS: Greater calcium burden is associated with a lower level of vascular inflammation and plaque vulnerability. A greater calcium burden may represent advanced stable plaque without significant inflammatory activity. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194).

Impact of morphofunctional assessment with quantitative flow ratio and optical coherence tomography in patients with acute coronary syndromes.

BACKGROUND: Combining morphological and physiological evaluations might improve the risk stratification of patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) culprit lesions. AIMS: We aimed to investigate the clinical utility of morphofunctional evaluation after PCI for identifying ACS patients with increased risk of subsequent clinical events. METHODS: We retrospectively studied 298 consecutive ACS patients who had undergone optical coherence tomography (OCT)-guided PCI. We performed OCT-based morphological analysis and quantitative flow ratio (QFR)-based physiological assessment immediately after PCI. The non-culprit segment (NCS) was defined as the most stenotic untreated segment in the culprit vessel. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, and ischaemia-driven target vessel revascularisation. RESULTS: During a median follow-up period of 990 days, 42 patients experienced TVF. Cox regression analysis revealed that the presence of thin-cap fibroatheroma (TCFA) in the NCS and a low post-PCI QFR, or the presence of TCFA in the NCS and a high ΔQFR in the NCS (QFRNCS), were independently associated with TVF. The subgroup with TCFA in the NCS and a low post-PCI QFR had a significantly higher incidence of TVF (75%) than the other subgroups, and those with TCFA in the NCS and a high ΔQFRNCS had a significantly higher incidence of TVF (86%) than the other subgroups. The integration of TCFA in NCS, post-PCI QFR, and ΔQFRNCS with traditional risk factors significantly enhanced the identification of subsequent TVF cases. CONCLUSIONS: Combining post-PCI OCT and QFR evaluation may enhance risk stratification for ACS patients after successful PCI, particularly in predicting subsequent TVF.

Overview of the 88th Annual Scientific Meeting of the Japanese Circulation Society (JCS2024)　- The Future of Cardiology - Challenges in Overcoming Cardiovascular Disease.

The 88thAnnual Scientific Meeting of the Japanese Circulation Society (JCS2024) was held from Friday, March 8thto Sunday, March 10thin Kobe, Japan. The main theme of this 3-day meeting was "The Future of Cardiology: Challenges in Overcoming Cardiovascular Disease". As COVID-19 has been finally conquered, with revision of its categorization under the Infectious Disease Control Law and relaxation of infection prevention measures, it was once again possible to have face-to-face presentations and lively discussion. JCS2024 was a major success, with 19,209 participants and attendees, thanks to the greatly appreciated cooperation and support from all affiliates.

Artificial Intelligence-Enabled Quantitative Coronary Plaque and Hemodynamic Analysis for Predicting Acute Coronary Syndrome.

BACKGROUND: A lesion-level risk prediction for acute coronary syndrome (ACS) needs better characterization. OBJECTIVES: This study sought to investigate the additive value of artificial intelligence-enabled quantitative coronary plaque and hemodynamic analysis (AI-QCPHA). METHODS: Among ACS patients who underwent coronary computed tomography angiography (CTA) from 1 month to 3 years before the ACS event, culprit and nonculprit lesions on coronary CTA were adjudicated based on invasive coronary angiography. The primary endpoint was the predictability of the risk models for ACS culprit lesions. The reference model included the Coronary Artery Disease Reporting and Data System, a standardized classification for stenosis severity, and high-risk plaque, defined as lesions with ≥2 adverse plaque characteristics. The new prediction model was the reference model plus AI-QCPHA features, selected by hierarchical clustering and information gain in the derivation cohort. The model performance was assessed in the validation cohort. RESULTS: Among 351 patients (age: 65.9 ± 11.7 years) with 2,088 nonculprit and 363 culprit lesions, the median interval from coronary CTA to ACS event was 375 days (Q1-Q3: 95-645 days), and 223 patients (63.5%) presented with myocardial infarction. In the derivation cohort (n = 243), the best AI-QCPHA features were fractional flow reserve across the lesion, plaque burden, total plaque volume, low-attenuation plaque volume, and averaged percent total myocardial blood flow. The addition of AI-QCPHA features showed higher predictability than the reference model in the validation cohort (n = 108) (AUC: 0.84 vs 0.78; P < 0.001). The additive value of AI-QCPHA features was consistent across different timepoints from coronary CTA. CONCLUSIONS: AI-enabled plaque and hemodynamic quantification enhanced the predictability for ACS culprit lesions over the conventional coronary CTA analysis. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary Computed Tomography Angiography and Computational Fluid Dynamics II [EMERALD-II]; NCT03591328).

Stent sizing by coronary CT angiography compared with optical coherence tomography.

BACKGROUND: Coronary CT angiography (CCTA) is well-established for diagnosis and stratification of coronary artery disease (CAD). Its usefulness in guiding percutaneous coronary interventions (PCI) and stent sizing is unknown. METHODS: This is a sub-analysis of the Precise Percutaneous Coronary Intervention Plan (P3) study (NCT03782688). We analyzed 65 vessels with matched CCTA and pre-PCI optical coherence tomography (OCT) assessment. The CCTA-guided stent size was defined by the mean distal reference lumen diameter rounded up to the nearest stent diameter. The OCT lumen-guided stent size was the mean distal reference lumen diameter rounded to the closest stent diameter. The agreement on stent diameters was determined with Kappa statistics, Passing-Bablok regression analysis, and the Bland-Altman method. RESULTS: The distal reference lumen diameter by CCTA and OCT were 2.75 â€‹± â€‹0.53 â€‹mm and 2.72 â€‹± â€‹0.55 â€‹mm (mean difference 0.06, limits of agreement -0.7 to 0.82). There were no proportional or systematic differences (coefficient A 1.06, 95% CI 0.84 to 1.3 and coefficient B -0.22, 95% CI -0.83 to 0.36) between methods. The agreement between the CCTA and OCT stent size was substantial (Cohen's weighted Kappa 0.74, 95% CI 0.64 to 0.85). Compared to OCT stent diameter, CCTA stent size was concordant in 52.3% of the cases; CCTA overestimated stent size in 20.0% and underestimated in 27.7%. CONCLUSION: CCTA accurately assessed the reference vessel diameter used for stent sizing. CCTA-based stent sizing showed a substantial agreement with OCT. CCTA allows for PCI planning and may aid in selecting stent diameter.

Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute Coronary Syndrome in Humans-Brief Report.

BACKGROUND: Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS. METHODS: We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis. RESULTS: CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells. CONCLUSIONS: For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS. REGISTRATION: URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.

Diagnostic accuracy of Murray law-based quantitative flow ratio in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

BACKGROUND: Murray law-based quantitative flow ratio (µQFR) is a novel computational method that enables accurate estimation of fractional flow reserve (FFR) using a single angiographic projection. However, its diagnostic value in patients with severe aortic stenosis (AS) remains unclear. METHOD: We included 25 consecutive patients who underwent transcatheter aortic valve replacement (TAVR) for severe AS with intermediate or greater (30-90%) coronary artery disease (CAD). Pre- and post-TAVR µQFR, QFR, instantaneous flow reserve (iFR), and post-TAVR invasive FFR values were measured. We evaluated the diagnostic performance of pre-TAVR µQFR, QFR, and iFR using post-TAVR FFR ≤ 0.80 as a reference standard of ischemia. RESULT: Pre-TAVR µQFR was significantly correlated with post-TAVR FFR (r = 0.73, p < 0.0001). The area under the curve of pre-TAVR µQFR on post-TAVR FFR ≤ 0.8 was 0.91 (95% confidence interval [CI] 0.77-0.98), comparable to that of pre-TAVR iFR (0.86 [95% CI 0.71-0.98], p = 0.97). The accuracy, sensitivity, specificity, and positive and negative predictive values of pre-TAVR µQFR on post-TAVR FFR ≤ 0.8 were 84.2% (95% CI 68.7-93.4), 61.6% (95% CI 31.6-86.1), 96.0% (95% CI 79.6-99.9), 88.9% (95% CI 52.9-98.3), and 82.8% (95% CI 70.6-90.6), respectively. For pre-TAVR iFR, these values were 76.5% (95% CI 58.8-89.3), 90.9% (95% CI 58.7-99.8), 69.6% (95% CI 47.1-86.8), 58.8% (95% CI 42.8-73.1), and 94.1% (95% CI 70.8-99.1), respectively. CONCLUSION: µQFR could be useful for the physiological evaluation of patients with severe AS with concomitant CAD.

Intravascular Imaging Findings After PCI in Patients With Focal and Diffuse Coronary Artery Disease.

BACKGROUND: Following percutaneous coronary intervention (PCI), optical coherence tomography provides prognosis information. The pullback pressure gradient is a novel index that discriminates focal from diffuse coronary artery disease based on fractional flow reserve pullbacks. We sought to investigate the association between coronary artery disease patterns, defined by coronary physiology, and optical coherence tomography after stent implantation in stable patients undergoing PCI. METHODS AND RESULTS: This multicenter, prospective, single-arm study was conducted in 5 countries (NCT03782688). Subjects underwent motorized fractional flow reserve pullbacks evaluation followed by optical coherence tomography-guided PCI. Post-PCI optical coherence tomography minimum stent area, stent expansion, and the presence of suboptimal findings such as incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were compared between patients with focal versus diffuse disease. Overall, 102 patients (105 vessels) were included. Fractional flow reserve before PCI was 0.65±0.14, pullback pressure gradient was 0.66±0.14, and post-PCI fractional flow reserve was 0.88±0.06. The mean minimum stent area was 5.69±1.99 mm2 and was significantly larger in vessels with focal disease (6.18±2.12 mm2 versus 5.19±1.72 mm2, P=0.01). After PCI, incomplete stent apposition, stent edge dissection, and irregular tissue protrusion were observed in 27.6%, 10.5%, and 51.4% of the cases, respectively. Vessels with focal disease at baseline had a lower prevalence of incomplete stent apposition (11.3% versus 44.2%, P=0.002) and more irregular tissue protrusion (69.8% versus 32.7%, P<0.001). CONCLUSIONS: Baseline coronary pathophysiological patterns are associated with suboptimal imaging findings after PCI. Patients with focal disease had larger minimum stent area and a higher incidence of tissue protrusion, whereas stent malapposition was more frequent in patients with diffuse disease.

Impact of Pericoronary Adipose Tissue Attenuation on Periprocedural Myocardial Injury in Patients With Chronic Coronary Syndrome.

BACKGROUND: Perivascular inflammation contributes to the development of atherosclerosis and microcirculatory dysfunction. Pericoronary adipose tissue (PCAT) attenuation, measured by coronary computed tomography angiography, is a potential indicator of coronary inflammation. However, the relationship between PCAT attenuation, microcirculatory dysfunction, and periprocedural myocardial injury (PMI) remains unclear. METHODS AND RESULTS: Patients with chronic coronary syndrome who underwent coronary computed tomography angiography before percutaneous coronary intervention were retrospectively identified. PCAT attenuation and adverse plaque characteristics were assessed using coronary computed tomography angiography. The extent of microcirculatory dysfunction was evaluated using the angio-based index of microcirculatory resistance before and after percutaneous coronary intervention. Overall, 125 consecutive patients were included, with 50 experiencing PMI (PMI group) and 75 without PMI (non-PMI group). Multivariable analysis showed that older age, higher angio-based index of microcirculatory resistance, presence of adverse plaque characteristics, and higher lesion-based PCAT attenuation were independently associated with PMI occurrence (odds ratio [OR], 1.07 [95% CI, 1.01-1.13]; P=0.02; OR, 1.06 [95% CI, 1.00-1.12]; P=0.04; OR, 6.62 [95% CI, 2.13-20.6]; P=0.001; and OR, 2.89 [95% CI, 1.63-5.11]; P<0.001, respectively). High PCAT attenuation was correlated with microcirculatory dysfunction before and after percutaneous coronary intervention and its exacerbation during percutaneous coronary intervention. Adding lesion-based PCAT attenuation to the presence of adverse plaque characteristics improved the discriminatory and reclassification ability in predicting PMI. CONCLUSIONS: Adding PCAT attenuation at the culprit lesion level to coronary computed tomography angiography-derived adverse plaque characteristics may provide incremental benefit in identifying patients at risk of PMI. Our results highlight the importance of microcirculatory dysfunction in PMI development, particularly in the presence of lesions with high PCAT attenuation. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000057722; Unique identifier: UMIN000050662.

Impact of coronary CT image quality on the accuracy of the FFRCT Planner.

OBJECTIVE: To assess the accuracy of a virtual stenting tool based on coronary CT angiography (CCTA) and fractional flow reserve (FFR) derived from CCTA (FFRCT Planner) across different levels of image quality. MATERIALS AND METHODS: Prospective, multicenter, single-arm study of patients with chronic coronary syndromes and lesions with FFR ≤ 0.80. All patients underwent CCTA performed with recent-generation scanners. CCTA image quality was adjudicated using the four-point Likert scale at a per-vessel level by an independent committee blinded to the FFRCT Planner. Patient- and technical-related factors that could affect the FFRCT Planner accuracy were evaluated. The FFRCT Planner was applied mirroring percutaneous coronary intervention (PCI) to determine the agreement with invasively measured post-PCI FFR. RESULTS: Overall, 120 patients (123 vessels) were included. Invasive post-PCI FFR was 0.88 ± 0.06 and Planner FFRCT was 0.86 ± 0.06 (mean difference 0.02 FFR units, the lower limit of agreement (LLA) - 0.12, upper limit of agreement (ULA) 0.15). CCTA image quality was assessed as excellent (Likert score 4) in 48.3%, good (Likert score 3) in 45%, and sufficient (Likert score 2) in 6.7% of patients. The FFRCT Planner was accurate across different levels of image quality with a mean difference between FFRCT Planner and invasive post-PCI FFR of 0.02 ± 0.07 in Likert score 4, 0.02 ± 0.07 in Likert score 3 and 0.03 ± 0.08 in Likert score 2, p = 0.695. Nitrate dose ≥ 0.8mg was the only independent factor associated with the accuracy of the FFRCT Planner (95%CI - 0.06 to - 0.001, p = 0.040). CONCLUSION: The FFRCT Planner was accurate in predicting post-PCI FFR independent of CCTA image quality. CLINICAL RELEVANCE STATEMENT: Being accurate in predicting post-PCI FFR across a wide spectrum of CT image quality, the FFRCT Planner could potentially enhance and guide the invasive treatment. Adequate vasodilation during CT acquisition is relevant to improve the accuracy of the FFRCT Planner. KEY POINTS: • The fractional flow reserve derived from coronary CT angiography (FFRCT) Planner is a novel tool able to accurately predict fractional flow reserve after percutaneous coronary intervention. • The accuracy of the FFRCT Planner was confirmed across a wide spectrum of CT image quality. Nitrates dose at CT acquisition was the only independent predictor of its accuracy. • The FFRCT Planner could potentially enhance and guide the invasive treatment.

Diagnostic Accuracy of Pre-Transcatheter Aortic Valve Replacement Nitroglycerin-Free Fractional Flow Reserve-Computed Tomography-Based Physiological Assessment in Patients With Severe Aortic Stenosis for Predicting Post-Transcatheter Aortic Valve Replacement Ischemia.

BACKGROUND: Fractional flow reserve-computed tomography (FFRCT) has not been validated in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) for coronary artery disease due to theoretical difficulties in using nitroglycerin for such patients.Methods and Results: In this single-center study, we prospectively enrolled 21 patients (34 vessels) and performed pre-TAVR FFRCTwithout nitroglycerin, pre-TAVR invasive instantaneous wave-free ratio (iFR) measurements, and post-TAVR FFR measurements using a pressure wire. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of pre-TAVR FFRCT≤0.80 to predict post-TAVR invasive FFR ≤0.80 were 82%, 83%, 82%, 71%, and 90%, respectively. A receiver operating characteristic analysis demonstrated an optimal cutoff of 0.78 for pre-TAVR FFRCTto indicate post-TAVR FFR ≤0.80, with an area under the curve (AUC) of 0.84, and the counterpart cutoff of pre-TAVR iFR was 0.89 with an AUC of 0.86. CONCLUSIONS: FFRCTwithout nitroglycerin could be a useful non-invasive imaging modality for assessing the severity of coronary artery lesions in patients with severe AS.

Influence of intracoronary hemodynamic forces on atherosclerotic plaque phenotypes.

BACKGROUND AND AIMS: Coronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition. METHODS: Prospective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained. RESULTS: One hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56-0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30-0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6-24.3] vs. 7.03 [4.8-11.7] Pa, p < 0.001) and TSVI (163.9 [117.6-249.2] vs. 76.8 [23.1-140.9] m-1, p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00-1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19-9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11-7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002). CONCLUSIONS: Focal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features. CLINICAL TRIAL REGISTRATION: https://clinicaltrials,gov/ct2/show/NCT03782688.

Coronary air embolism during transcatheter patent foramen ovale closure for platypnea-orthodeoxia syndrome in a patient with severe respiratory disorder: a case report.

Background: Coronary air embolism (CAE) is a rare and life-threatening complication of endovascular procedures, mostly due to procedure-related causes. Case summary: A 70-year-old man with severe respiratory disorder presented with patent foramen ovale (PFO)-related platypnea-orthodeoxia syndrome (POS). Transcatheter PFO closure was performed under local anaesthesia and intracardiac echocardiographic guidance. After a 5-Fr catheter was passed through the PFO via a 7-Fr femoral vein sheath, the patient suddenly coughed and breathed deeply. Thereafter, intracardiac echocardiography showed massive microbubbles in all cardiac chambers and the ascending aorta, and an electrocardiogram showed ST-segment elevations in the anterior and inferior leads. Emergency coronary angiography confirmed occlusion of the mid-left anterior descending artery, suggesting CAE. As the intracoronary infusion of saline, nitroglycerine, and nicorandil was ineffective, we performed air aspiration using a thrombectomy device, achieving coronary blood flow improvement and ST-segment resolution. Thereafter, positive pressure support using manual bag-valve-mask ventilation under intravenous sedation supported successful transcatheter PFO closure without further air embolization. Discussion: In this case with severe respiratory dysfunction, spontaneous deep breathing (spontaneous Valsalva manoeuvre) caused negative intrathoracic pressure and large drops in intravascular pressure. This phenomenon might have induced air contamination during device advancement, either by entrapping or leaving residual air in the gaps between the catheter and the sheath. Additionally, PFO with right-to-left shunts is more likely to cause paradoxical air embolization. Thus, the spontaneous Valsalva manoeuvre should be avoided with appropriate respiratory management to prevent paradoxical air embolization, including CAE, during transcatheter PFO closure under local anaesthesia in severe respiratory dysfunction patients.

Diagnosis and Prognostic Value of the Underlying Cause of Acute Coronary Syndrome in Optical Coherence Tomography-Guided Emergency Percutaneous Coronary Intervention.

Background The prognostic impact of optical coherence tomography-diagnosed culprit lesion morphology in acute coronary syndrome (ACS) has not been systematically examined in real-world settings. Methods and Results This investigator-initiated, prospective, multicenter, observational study was conducted at 22 Japanese hospitals to identify the prevalence of underlying ACS causes (plaque rupture [PR], plaque erosion [PE], and calcified nodules [CN]) and their impact on clinical outcomes. Patients with ACS diagnosed within 24 hours of symptom onset undergoing emergency percutaneous coronary intervention were enrolled. Optical coherence tomography-guided percutaneous coronary intervention recipients were assessed for underlying ACS causes and followed up for major adverse cardiac events (cardiovascular death, myocardial infarction, heart failure, or ischemia-driven revascularization) at 1 year. Of 1702 patients with ACS, 702 (40.7%) underwent optical coherence tomography-guided percutaneous coronary intervention for analysis. PR, PE, and CN prevalence was 59.1%, 25.6%, and 4.0%, respectively. One-year major adverse cardiac events occurred most frequently in patients with CN (32.1%), followed by PR (12.4%) and PE (6.2%) (log-rank P<0.0001), primarily driven by increased cardiovascular death (CN, 25.0%; PR, 0.7%; PE, 1.1%; log-rank P<0.0001) and heart failure trend (CN, 7.1%; PR, 6.8%; PE, 2.2%; log-rank P<0.075). On multivariate Cox regression analysis, the underlying ACS cause was associated with 1-year major adverse cardiac events (CN [hazard ratio (HR), 4.49 [95% CI, 1.35-14.89], P=0.014]; PR (HR, 2.18 [95% CI, 1.05-4.53], P=0.036]; PE as reference). Conclusions Despite being the least common, CN was a clinically significant underlying ACS cause, associated with the highest future major adverse cardiac events risk, followed by PR and PE. Future studies should evaluate the possibility of ACS underlying cause-based optical coherence tomography-guided optimization.

Impact of coronary bifurcation angle on stent malapposition in a randomized comparison between proximal optimization technique followed by side branch dilatation and kissing balloon inflation.

Background: The impact of coronary bifurcation angle (BA) on incomplete stent apposition (ISA) after crossover stenting followed by side branch (SB) intervention has not been established. Methods: A total of 100 crossover stentings randomly treated with proximal optimization technique followed by short balloon dilation in the SB (POT-SBD group, 48 patients) and final kissing balloon technique (KBT group, 52 patients) were analyzed in the PROPOT trial. Major ISA with maximum distance > 400 µm and its location was determined using optical coherence tomography before SB intervention and at the final procedure. The BA was defined as the angle between the distal main vessel and SB. Optimal POT was determined when the difference in stent volume index between the proximal and distal bifurcation was greater than the median value (0.86 mm3/mm) before SB intervention. Result: Major ISA was more frequently observed in the POT-SBD than in the KBT group (35% versus 17%, p < 0.05). In the POT-SBD group, worsening ISA after SBD was prominent at the distal bifurcation. The BA was an independent predictor of major ISA (odds ratio 1.04, 95% confidence interval 1.00-1.07, p < 0.05) with a cut-off value of 59.5° (p < 0.05). However, the cases treated with optimal POT in the short BA (<60°) indicated the lowest incidence of major ISA. In the KBT group, BA had no significant impact. Conclusion: A wide BA has a potential risk for the occurrence of major ISA after POT followed by SBD in coronary bifurcation stenting.