Determination of lipid-rich plaques by artificial intelligence-enabled quantitative computed tomography using near-infrared spectroscopy as reference.

BACKGROUND AND AIMS: Artificial intelligence quantitative CT (AI-QCT) determines coronary plaque morphology with high efficiency and accuracy. Yet, its performance to quantify lipid-rich plaque remains unclear. This study investigated the performance of AI-QCT for the detection of low-density noncalcified plaque (LD-NCP) using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). METHODS: The INVICTUS Registry is a multi-center registry enrolling patients undergoing clinically indicated coronary CT angiography and IVUS, NIRS-IVUS, or optical coherence tomography. We assessed the performance of various Hounsfield unit (HU) and volume thresholds of LD-NCP using maxLCBI4mm ≥ 400 as the reference standard and the correlation of the vessel area, lumen area, plaque burden, and lesion length between AI-QCT and IVUS. RESULTS: This study included 133 atherosclerotic plaques from 47 patients who underwent coronary CT angiography and NIRS-IVUS The area under the curve of LD-NCP<30HU was 0.97 (95% confidence interval [CI]: 0.93-1.00] with an optimal volume threshold of 2.30 mm3. Accuracy, sensitivity, and specificity were 94% (95% CI: 88-96%], 93% (95% CI: 76-98%), and 94% (95% CI: 88-98%), respectively, using <30 HU and 2.3 mm3, versus 42%, 100%, and 27% using <30 HU and >0 mm3 volume of LD-NCP (p < 0.001 for accuracy and specificity). AI-QCT strongly correlated with IVUS measurements; vessel area (r2 = 0.87), lumen area (r2 = 0.87), plaque burden (r2 = 0.78) and lesion length (r2 = 0.88), respectively. CONCLUSIONS: AI-QCT demonstrated excellent diagnostic performance in detecting significant LD-NCP using maxLCBI4mm ≥ 400 as the reference standard. Additionally, vessel area, lumen area, plaque burden, and lesion length derived from AI-QCT strongly correlated with respective IVUS measurements.

Physiology-guided PCI versus CABG for left main coronary artery disease: insights from the DEFINE-LM registry.

There have been no studies comparing clinical outcomes of physiology-guided revascularization in patients with unprotected left main coronary disease (ULMD) between percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG). The aim of this study was to assess the long-term clinical outcomes between PCI and CABG of patients with physiologically significant ULMD. From an international multicenter registry of ULMD patients interrogated with instantaneous wave-free ratio (iFR), we analyzed data from 151 patients (85 PCI vs. 66 CABG) who underwent revascularization according to the cutoff value of iFR ≤ 0.89. Propensity score matching was employed to adjust for baseline clinical characteristics. The primary endpoint was a composite of all-cause death, non-fatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were the individual components of the primary endpoint. Mean age was 66.6 (± 9.2) years, 79.2% male. Mean SYNTAX score was 22.6 (± 8.4) and median iFR was 0.83 (IQR 0.74-0.87). After performing propensity score matching analysis, 48 patients treated with CABG were matched to those who underwent PCI. At a median follow-up period of 2.8 years, the primary endpoint occurred in 8.3% in PCI group and 20.8% in CABG group, respectively (HR 3.80; 95% CI 1.04-13.9; p = 0.043). There was no difference in each component of the primary event (p > 0.05 for all). Within the present study, iFR-guided PCI was associated with lower cardiovascular events rate in patients with ULMD and intermediate SYNTAX score, as compared to CABG. State-of-the-art PCI vs. CABG for ULMD. Study design and primary endpoint in patients with physiologically significant ULMD. MACE was defined as the composite of all-cause death, non-fatal myocardial infarction, and target lesion revascularization. The blue line denotes the PCI arm, and the red line denotes the CABG arm. PCI was associated with significantly lower risk of MACE than CABG. CABG: coronary artery bypass grafting; iFR: instantaneous wave-free ratio; MACE: major adverse cardiovascular events; PCI: percutaneous coronary intervention; ULMD: unprotected left main coronary artery disease.

Diagnostic Accuracy of Artificial Intelligence-Based Angiography-Derived Fractional Flow Reserve Using Pressure Wire-Based Fractional Flow Reserve as a Reference.

BACKGROUND: Angiographic fractional flow reserve (angioFFR) is a novel artificial intelligence (AI)-based angiography-derived fractional flow reserve (FFR) application. We investigated the diagnostic accuracy of angioFFR to detect hemodynamically relevant coronary artery disease.Methods and Results: Consecutive patients with 30-90% angiographic stenoses and invasive FFR measurements were included in this prospective, single-center study conducted between November 2018 and February 2020. Diagnostic accuracy was assessed using invasive FFR as the reference standard. In patients undergoing percutaneous coronary intervention, gradients of invasive FFR and angioFFR in the pre-senting segments were compared. We assessed 253 vessels (200 patients). The accuracy of angioFFR was 87.7% (95% confidence interval [CI] 83.1-91.5%), with a sensitivity of 76.8% (95% CI 67.1-84.9%), specificity of 94.3% (95% CI 89.5-97.4%), and area under the curve of 0.90 (95% CI 0.86-0.93%). AngioFFR was well correlated with invasive FFR (r=0.76; 95% CI 0.71-0.81; P<0.001). The agreement was 0.003 (limits of agreement: -0.13, 0.14). The FFR gradients of angioFFR and invasive FFR were comparable (n=51; mean [±SD] 0.22±0.10 vs. 0.22±0.11, respectively; P=0.87). CONCLUSIONS: AI-based angioFFR showed good diagnostic accuracy for detecting hemodynamically relevant stenosis using invasive FFR as the reference standard. The gradients of invasive FFR and angioFFR in the pre-stenting segments were comparable.

Physiological Approach for Coronary Artery Bifurcation Disease: Position Statement by Korean, Japanese, and European Bifurcation Clubs.

Coronary artery bifurcation lesions are frequently encountered in cardiac catheterization laboratories and are associated with more complex procedures and worse clinical outcomes than nonbifurcation lesions. Therefore, anatomical and physiological assessment of bifurcation lesions before, during, and after percutaneous coronary intervention is of paramount clinical importance. Physiological assessment can help interventionalists appreciate the hemodynamic significance of coronary artery disease and guide ischemia-directed revascularization. However, it is important to understand that the physiological approach for bifurcation disease is more important than simply using physiological indexes for its assessment. This joint consensus document by the Korean, Japanese, and European bifurcation clubs presents the concept of a physiological approach for coronary bifurcation lesions, as well as current knowledge, practical tips, pitfalls, and future directions of applying physiological indexes in bifurcation percutaneous coronary intervention. This document aims to guide interventionalists in performing appropriate physiology-based assessments and treatment decisions for coronary bifurcation lesions.

Fractional Flow Reserve Versus Instantaneous Wave-Free Ratio in Assessment of Lesion Hemodynamic Significance and Explanation of their Discrepancies. International, Multicenter and Prospective Trial: The FiGARO Study.

Background The FiGARO (FFR versus iFR in Assessment of Hemodynamic Lesion Significance, and an Explanation of Their Discrepancies) trial is a prospective registry searching for predictors of fractional flow reserve/instantaneous wave-free ratio (FFR/iFR) discrepancy. Methods and Results FFR/iFR were analyzed using a Verrata wire, and coronary flow reserve was analyzed using a Combomap machine (both Philips-Volcano). The risk polymorphisms for endothelial nitric oxide synthase and for heme oxygenase-1 were analyzed. In total, 1884 FFR/iFR measurements from 1564 patients were included. The FFR/iFR discrepancy occurred in 393 measurements (20.9%): FFRp (positive)/iFRn (negative) type (264 lesions, 14.0%) and FFRn/iFRp (129 lesions, 6.8%) type. Coronary flow reserve was measured in 343 lesions, correlating better with iFR (R=0.56, P<0.0001) than FFR (R=0.36, P<0.0001). The coronary flow reserve value in FFRp/iFRn lesions (2.24±0.7) was significantly higher compared with both FFRp/iFRp (1.39±0.36), and FFRn/iFRn lesions (1.8±0.64, P<0.0001). Multivariable logistic regression analysis confirmed (1) sex, age, and lesion location in the right coronary artery as predictors for FFRp/iFRn discrepancy; and (2) hemoglobin level, smoking, and renal insufficiency as predictors for FFRn/iFRp discrepancy. The FFRn/iFRp type of discrepancy was significantly more frequent in patients with both risk types of polymorphisms (endothelial nitric oxide synthaser+heme oxygenase-1r): 8 patients (24.2%) compared with FFRp/iFRn type of discrepancy: 2 patients (5.9%), P=0.03. Conclusions Predictors for FFRp/iFRn discrepancy were sex, age, and location in the right coronary artery. Predictors for FFRn/iFRp were hemoglobin level, smoking, and renal insufficiency. The risk type of polymorphism in endothelial nitric oxide synthase and heme oxygenase-1 genes was more frequently found in patients with FFRn/iFRp type of discrepancy. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03033810.

Clinical impact of PCSK9 inhibitor on stabilization and regression of lipid-rich coronary plaques: a near-infrared spectroscopy study.

AIMS: This study aimed to determine the effects of a proprotein convertase subtilisin-kexin type 9 inhibitor (PCSK9i) on coronary plaque volume and lipid components in patients with a history of coronary artery disease (CAD). METHODS AND RESULTS: This prospective, open-label, single-centre study analysed non-culprit coronary segments using near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) at baseline and follow-up angiography. Following changes in the lipid-lowering treatment based on the most recent guideline, the enrolled subjects were divided into two groups: treatment with PCSK9i and statins (PCSK9i: 21 patients and 40 segments) and statins only (control: 32 patients and 50 segments). The absolute and percent LDL-C reductions were significantly greater in the PCSK9i group than in the control group (between group difference: 59.3 mg/dL and 46.4%; P < 0.001 for both). The percent reduction in normalized atheroma volume and absolute reduction in percent atheroma volume (PAV) were also significantly greater in the PCSK9i group (P < 0.001 for both). Furthermore, the PCSK9i group showed greater regression of maximal lipid core burden index for each of the 4-mm segments (maxLCBI4mm) than the control group (57.0 vs. 25.5; P = 0.010). A significant linear correlation was found between the percent changes in LDL-C and maxLCBI4mm (r = 0.318; P = 0.002), alongside the reduction in PAV (r = 0.386; P < 0.001). CONCLUSION: The lipid component of non-culprit coronary plaques was significantly decreased by PCSK9i. The effects of statin combined with PCSK9i might be attributed to the stabilization and regression of residual vulnerable coronary plaques in patients with CAD.

Stress Myocardial Perfusion Imaging Interpretation From the Viewpoint of Fractional Flow Reserve.

BACKGROUND: Myocardial perfusion imaging (MPI) and fractional flow reserve (FFR) are established approaches to the assessment of myocardial ischemia. Recently, various FFR cutoff values were proposed, but the diagnostic accuracy of MPI in identifying positive FFR using various cutoff values is not well established.Methods and Results:We retrospectively studied 273 patients who underwent stress MPI and FFR within a 3-month period. Results for FFR were obtained from 218 left anterior descending artery (LAD) lesions and 207 non-LAD lesions. Stress MPI and FFR demonstrated a good correlation in the detection of myocardial ischemia. However, the positive predictive value (PPV) of FFR for detecting MPI-positive lesions at the optimal FFR thresholds was insufficient (44% for LAD and 65% for non-LAD lesions). This was caused by a sharp drop in PPV at an FFR threshold of 0.7 or more. Notably, 41% of the lesions with normal MPI demonstrated FFRs <0.80. However, MPI-negative lesions had an extremely low lesion rate with FFR <0.65 (6%). Conversely, 78% and 41% of MPI-positive lesions had FFR <0.80 and <0.65, respectively. CONCLUSIONS: The data confirmed that decisions based on MPI are reasonable because MPI-negative patients have an extremely low rate of lesions with a FFR below the cutoff point for a hard event, and MPI-positive lesions include many lesions with FFR <0.65.

Heat shock response enhanced by cell culture treatment in mouse embryonic stem cell-derived proliferating neural stem cells.

Cells have a regulatory mechanism known as heat shock (HS) response, which induces the expression of HS genes and proteins in response to heat and other cellular stresses. Exposure to moderate HS results in beneficial effects, such as thermotolerance and promotes survival, whereas excessive HS causes cell death. The effect of HS on cells depends on both exogenous factors, including the temperature and duration of heat application, and endogenous factors, such as the degree of cell differentiation. Neural stem cells (NSCs) can self-renew and differentiate into neurons and glial cells, but the changes in the HS response of symmetrically proliferating NSCs in culture are unclear. We evaluated the HS response of homogeneous proliferating NSCs derived from mouse embryonic stem cells during the proliferative phase and its effect on survival and cell death in vitro. The number of adherent cells and the expression ratios of HS protein (Hsp)40 and Hsp70 genes after exposure to HS for 20 min at temperatures above 43°C significantly increased with the extension of the culture period before exposure to HS. In contrast, caspase activity was significantly decreased by extension of the culture period before exposure to HS and suppressed the decrease in cell viability. These results suggest that the culture period before HS remarkably affects the HS response, influencing the expression of HS genes and cell survival of proliferating NSCs in culture.

Determination of the Optimal Measurement Point for Fractional Flow Reserve Derived From CTA Using Pressure Wire Assessment as Reference.

BACKGROUND. For clinical decision making, it was recently recommended that values of fractional flow reserve (FFR) derived from coronary CTA (FFRCT) be measured 1-2 cm distal to the stenosis, given the potential for overestimation of ischemia when FFRCT values at far distal segments are used. Supporting data are, however, lacking. OBJECTIVE. The purpose of the present study was to evaluate the diagnostic performance of FFRCT values measured 1-2 cm distal to the stenosis and at more distal locations relative to invasive FFR values. METHODS. FFRCT and invasive FFR values for 365 vessels in 253 patients identified from the Assessing Diagnostic Value of Noninvasive FFRCT in Coronary Care (ADVANCE) registry were prospectively assessed. FFRCT values were measured 1-2 cm distal to the stenosis and at the pressure wire position and far distal segments. The diagnostic accuracy of FFRCT was assessed on the basis of the ROC AUC. The AUC of FFRCT was calculated using FFRCT as an explanatory variable and an invasive FFR of 0.80 or less as the dichotomous dependent variable. RESULTS. The AUC of FFRCT values measured 1-2 cm distal to the stenosis (0.85; 95% CI, 0.80-0.88) was higher (p = .002) than that of FFRCT values measured at far distal segments (0.80; 95% CI, 0.76-0.84) and similar (p = .16) to that of FFRCT values measured at the pressure wire position (0.86; 95% CI, 0.81-0.89). FFRCT values measured 1-2 cm distal to the stenosis and at far distal segments had sensitivity of 87% versus 92% (p = .003), specificity of 73% versus 42% (p < .001), PPV of 75% versus 59% (p < .001), and NPV of 86% versus 85% (p = .72), respectively. Subgroup analyses of lesions of the left anterior descending coronary artery, left circumflex coronary artery, and right coronary artery all showed improved specificity and PPV (all p < .005) for FFRCT values measured 1-2 cm distal to the stenosis compared with values measured at the pressure wire position. However, the AUC was higher for measurements obtained 1-2 cm distal to the stenosis versus those obtained at far distal segments, for left anterior descending coronary artery lesions (p < .001) but not for left circumflex coronary artery lesions (p = .27) or right coronary artery lesions (p = .91). CONCLUSION. The diagnostic performance of FFRCT values measured 1-2 cm distal to the stenosis was higher than that of FFRCT values measured at far distal segments and was similar to that of FFRCT values measured at the pressure wire position in evaluating ischemic status, particularly for left anterior descending coronary artery lesions. CLINICAL IMPACT. The present study supports recent recommendations from experts to use FFRCT measured 1-2 cm distal to the stenosis, rather than measurements obtained at far distal segments, in clinical decision making.

In vivo validation of resting full-cycle ratio and diastolic pressure ratio: simultaneous measurement with instantaneous wave-free ratio.

The diastolic pressure ratio (dPR) and resting full-cycle ratio (RFR) are considered to be almost identical to the instantaneous wave-free ratio (iFR) in the retrospective analysis of pooled data. The aim of this study was to investigate the direct comparison of iFR and these new resting indexes in real world practice. Two pressure wires were inserted and placed in the distal part of the same coronary artery. The measurement of the iFR and the other resting indexes was performed simultaneously. A total of 54 lesions from 23 patients were subject to physiological study. In 49 lesions, iFR and other resting indexes were also measured in hyperemic conditions. The general correlation between iFR and other resting indexes was excellent in both resting and hyperemic conditions (r2 = 0.99; mean difference - 0.001 ± 0.021; p < 0.001; and r2 = 0.99; mean difference - 0.012 ± 0.025; p < 0.001, respectively). This correlation was maintained in various subgroup analyses. A diagnostic change between iFR and other resting indexes occurred in three cases (3%) when a fixed cut-off point (≤ 0.89) was applied. There was no diagnostic change when a hybrid zone (0.86 ≤ iFR ≤ 0.93) was considered. The new resting indexes and iFR showed very high correlation in real world practice. A diagnostic change only occurred in three cases (3%) when a fixed cut-off point (≤ 0.89) was applied.

Comparisons of Nonhyperemic Pressure Ratios: Predicting Functional Results of Coronary Revascularization Using Longitudinal Vessel Interrogation.

OBJECTIVES: The aim of this study was to investigate the accuracy of pre-percutaneous coronary intervention (PCI) predicted nonhyperemic pressure ratios (NHPRs) with actual post-PCI NHPRs and to assess the efficacy of PCI strategy using pre-PCI NHPR pullback. BACKGROUND: Predicting the functional results of PCI is feasible using pre-PCI longitudinal vessel interrogation with the instantaneous wave-free ratio (iFR), a pressure-based, adenosine-free NHPR. However, the reliability of novel NHPRs (resting full-cycle ratio [RFR] and diastolic pressure ratio [dPR]) for this purpose remains uncertain. METHODS: In this prospective, multicenter, randomized controlled trial, vessels were randomly assigned to receive pre-PCI iFR, RFR, or dPR pullback (50 vessels each). The pre-PCI predicted NHPRs were compared with actual NHPRs after contemporary PCI using intravascular imaging. The number and the total length of treated lesions were compared between NHPR pullback-guided and angiography-guided strategies. RESULTS: The predicted NHPRs were strongly correlated with actual NHPRs: iFR, r = 0.83 (95% confidence interval: 0.72 to 0.90; p < 0.001); RFR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001), and dPR, r = 0.84 (95% confidence interval: 0.73 to 0.91; p < 0.001). The number and the total length of treated lesions were lower with the NHPR pullback strategy than with the angiography-guided strategy, leading to physiological improvement. CONCLUSIONS: Predicting functional PCI results on the basis of pre-procedural RFR and dPR pullbacks yields similar results to iFR. Compared with an angiography-guided strategy, a pullback-guided PCI strategy with any of the 3 NHPRs reduced the number and the total length of treated lesions. (Study to Examine Correlation Between Predictive Value and Post PCI Value of iFR, RFR and dPR; UMIN000033534).

Difference in functional assessment of individual stenosis severity in serial coronary lesions between resting and hyperemic pressure-wire pullback: Insights from the GIFT registry.

BACKGROUND: Identifying the individual hemodynamic significance of tandem coronary artery lesions can be complicated by the crosstalk phenomenon which occurs between serial stenoses under hyperemic conditions. Physiological assessments performed under resting conditions are considered to be, theoretically, less affected by the hemodynamic interaction between serial coronary stenoses. The purpose of this study was to assess whether pressure-wire (PW) pullback measurements at rest and during hyperemia provided different information as to which stenosis appeared to be most functionally significant. METHODS: In consecutive patients with angiographically discrete serial lesions, physiological lesion predominance (i.e. proximal or distal) was defined according to the pressure gradient along the vessels on PW-pullback trace. We used instantaneous wave-free ratio (iFR) based assessment as the reference standard and compared fractional flow reserve (FFR) based and hyperemic-iFR based lesion predominance. RESULTS: Eighty-eight vessels (70 patients, mean age 70.3 ± 9.4 years, 80% male) were included in this study. Median iFR, FFR and hyperemic-iFR were 0.85 (interquartile range [IQR]: 0.74 to 0.91), 0.73 (IQR: 0.65 to 0.80) and 0.60 (IQR: 0.49 to 0.71), respectively. When judged against iFR-pullback based physiological assessment, lesion predominance changed in 22.7% (20/88) in FFR and in 20.5% (18/88) in hyperemic-iFR, respectively. There was no statistical difference between FFR and hyperemic-iFR for the impact on these changes (p = 0.77). CONCLUSIONS: In serial coronary lesions, hyperemic PW-pullback disagreed with resting PW-pullback on the lesion-specific identification of ischemia in approximately 20% of cases, either in whole cardiac cycle or in wave-free period.

Per-Vessel Level Analysis of Fractional Flow Reserve and Instantaneous Wave-Free Ratio Discordance　- Insights From the AJIP Registry.

BACKGROUND: The per-vessel level impact of physiological pattern of disease on the discordance between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) has not been clarified.Methods and Results:Using the AJIP registry, vessels with FFR/iFR discordance (133/671 [19.8%]) were analyzed. In the left anterior descending artery (LAD), physiologically diffuse disease, as assessed by pressure-wire pullback, was associated with FFR-/iFR+ (83.3% [40/48]), while physiologically focal disease was associated with FFR+/iFR- (57.4% [31/54]), significantly (P<0.0001). These differences were not significant in non-LAD (P=0.17). CONCLUSIONS: The impact of physiological pattern of disease on FFR/iFR discordance is more pronounced in the LAD.

Endothelial dysfunction assessed by digital tonometry and discrepancy between fraction flow reserve and instantaneous wave free ratio.

Background: We tested whether the level of endothelial dysfunction assessed by digital tonometry, and expressed as reactive hyperemia index (RHI), is related to occurrences of a discrepancy between fractional flow reserve (FFR) and the instantaneous wave free ratio (iFR) (ClinicalTrials.gov identifier: NCT03033810).Methods: We examined patients with coronary stenosis in the range of 40-70%, assessed by both FFR and iFR (system Philips-Volcano) for stable angina. We included consecutive patients with FFR and iFR in one native coronary artery, and who had had no previous intervention.Results: We included 138 patients. Out of those, 24 patients (17.4%) had a negative FFR (with an FFR value >0.8) and positive iFR (with a iFR value ≤0.89) - designated the FFRn/iFRp discrepancy group, and 22 patients (15.9%) had a positive FFR (≤0.8) and negative iFR (>0.89) - designated the FFRp/iFRn discrepancy. RHI was higher in the discrepancy groups compared the group without discrepancy (1.73 ± 0.79 vs. 1.48 ± 0.50, p = 0.025). However, this finding was not confirmed in multivariant logistic regression analyses. Patients with any type of discrepancy differed from the agreement group by having a higher occurrence of diabetes mellitus [9 patients (21.4%) vs. 36 patients (39.6%), p = 0.029], active smoking (23 patients or 54.8% vs. 26 patients or 28.6%, p = 0.003) and lower use of calcium channel blockers (9 patients, 21.4%, vs. 43 patients, 46.7%, p = 0.004).Conclusion: The presence of endothelial dysfunction can be associated with a discrepancy in FFR/iFR. However, RHI correlated with risk factors of atherosclerosis, not with FFR or iFR.

QFR Versus FFR Derived From Computed Tomography for Functional Assessment of Coronary Artery Stenosis.

OBJECTIVES: The aim of this study was to compare diagnostic performance between quantitative flow ratio (QFR) derived from coronary angiography and fractional flow reserve derived from computed tomography (FFRCT) using fractional flow reserve (FFR) as the reference standard. BACKGROUND: QFR and FFRCT are recently developed, less invasive techniques for functional assessment of coronary artery disease. METHODS: QFR, FFRCT, and FFR were measured in 152 patients (233 vessels) with stable coronary artery disease. RESULTS: QFR was highly correlated with FFR (r = 0.78; p < 0.001), whereas FFRCT was moderately correlated with FFR (r = 0.63; p < 0.001). Both QFR and FFRCT showed moderately good agreement with FFR, presenting small values of mean difference but large values of root mean squared deviation (FFR-QFR, 0.02 ± 0.09; FFR-FFRCT, 0.03 ± 0.11). The sensitivity, specificity, positive predictive value, and negative predictive value of QFR ≤0.80 for predicting FFR ≤0.80 were 90%, 82%, 81%, and 90%, respectively. Those of FFRCT ≤0.80 for predicting FFR ≤0.80 were 82%, 70%, 70%, and 82%, respectively. The diagnostic accuracy of QFR ≤0.80 for predicting FFR ≤0.80 was 85% (95% confidence interval [CI]: 81% to 89%), whereas that of FFRCT ≤0.80 for predicting FFR ≤0.80 was 76% (95% CI: 70% to 80%). CONCLUSIONS: QFR and FFRCT showed significant correlation with FFR. Mismatches between QFR and FFR and between FFRCT and FFR were frequent.

Inhibition of epidermal growth factor receptor stimulates prolactin expression in primary culture of the mouse pituitary gland.

The roles of epidermal growth factor (EGF) in the regulation of prolactin (PRL) gene expression in the normal pituitary gland remain poorly understood. In the present study, the effects of EGF and an inhibitor of the EGF receptor, erlotinib, on PRL gene expression were examined both in the pituitary tumour cell line GH3 and in a primary culture of the mouse pituitary gland under similar experimental conditions. The results showed that EGF stimulated PRL expression in GH3 cells, but not in normal cells. Erlotinib was found to counteract EGF in GH3 cells inhibiting the PRL expression enhanced by EGF. By contrast, erlotinib induced an elevation in the PRL mRNA levels in the primary culture of the adult pituitary gland and the initiation of PRL production in the culture of the foetal pituitary gland in which PRL production had not yet occurred. Western blot analyses showed that EGF induced and erlotinib inhibited the activation of extracellular regulated protein kinase equally in GH3 and normal cells. These results suggest that the consequences of EGF receptor activation in normal PRL cells contradict those in adenomatous PRL cells.

Feasibility and safety of jailed-pressure wire technique using durable optical fiber pressure wire for intervention of coronary bifurcation lesions.

OBJECTIVES: The objective was to evaluate the safety, feasibility, and accuracy of the jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure dilatation using a non-compliant balloon after main vessel stenting. BACKGROUND: Fractional flow reserve (FFR) information can help interventionists determine whether they should treat a jailed-side branch (SB). However, re-crossing a pressure wire into a jailed-SB is sometimes technically difficult. METHODS: Fifty-one consecutive lesions from 48 patients who underwent the jailed-pressure wire technique were retrospectively investigated. The primary endpoint was complication rate and secondary endpoints included success rate of FFR measurement, incidence of wire disruption, and final drift rate. The usability of FFR for percutaneous coronary intervention of coronary bifurcation lesion was also evaluated. RESULTS: Median age of the patients was 69 years and 80.4% were men. The most frequent underlying disease was stable angina (70.6%) and 68.6% were type B2 lesions. Our main findings were: the procedure was performed successfully in all cases without any complications or wire disruption, FFR could be measured without significant final drift in 95.9% of cases, and FFR measurements helped interventionists determine whether to perform a final kissing balloon dilatation in 49.0% cases. CONCLUSIONS: The jailed-pressure wire technique using a durable optical fiber-based pressure wire with high-pressure post-dilatation maneuver was safe, feasible, and accurate.