A stepwise strategy integrating dynamic stress CT myocardial perfusion and deep learning-based FFRCT in the work-up of stable coronary artery disease.

OBJECTIVES: To validate a novel stepwise strategy in which computed tomography-derived fractional flow reserve (FFRCT) is restricted to intermediate stenosis on coronary computed tomography angiography (CCTA) and computed tomography myocardial perfusion imaging (CT-MPI) was reserved for vessels with gray zone FFRCT values. MATERIALS AND METHODS: This retrospective study included 87 consecutive patients (age, 58 ± 10 years; 70% male) who underwent CCTA, dynamic CT-MPI, interventional coronary angiography (ICA), and fractional flow reserve (FFR) for suspected or known coronary artery disease. FFRCT was computed using a deep learning-based platform. Three stepwise strategies (CCTA + FFRCT + CT-MPI, CCTA + FFRCT, CCTA + CT-MPI) were constructed and their diagnostic performance was evaluated using ICA/FFR as the reference standard. The proportions of vessels requiring further ICA/FFR measurement based on different strategies were noted. Furthermore, the net reclassification index (NRI) was calculated to ascertain the superior model. RESULTS: The CCTA + FFRCT + CT-MPI strategy yielded the lowest proportion of vessels requiring additional ICA/FFR measurement when compared to the CCTA + FFRCT and CCTA + CT-MPI strategies (12%, 22%, and 24%). The CCTA + FFRCT + CT-MPI strategy exhibited the highest accuracy for ruling-out (91%, 84%, and 85%) and ruling-in (90%, 85%, and 85%) functionally significant lesions. All strategies exhibited comparable sensitivity for ruling-out functionally significant lesions and specificity for ruling-in functionally significant lesions (p > 0.05). The NRI indicated that the CCTA + FFRCT + CT-MPI strategy outperformed the CCTA + FFRCT strategy (NRI = 0.238, p < 0.001) and the CCTA + CT-MPI strategy (NRI = 0.233%, p < 0.001). CONCLUSIONS: The CCTA + FFRCT + CT-MPI stepwise strategy was superior to the CCTA + FFRCT strategy and CCTA+ CT-MPI strategy by minimizing unnecessary invasive diagnostic catheterization without compromising the agreement rate with ICA/FFR. CLINICAL RELEVANCE STATEMENT: Our novel stepwise strategy facilitates greater confidence and accuracy when clinicians need to decide on interventional coronary angiography referral or deferral, reducing the burden of invasive investigations on patients. KEY POINTS: • A stepwise CCTA + FFRCT + CT-MPI strategy holds promise as a viable method to reduce the need for invasive diagnostic catheterization, while maintaining a high level of agreement with ICA/FFR. • The CCTA + FFRCT + CT-MPI strategy performed better than the CCTA + FFRCT and CCTA + CT-MPI strategies. • A stepwise CCTA + FFRCT + CT-MPI strategy allows to minimize unnecessary invasive diagnostic catheterization and helps clinicians to referral or deferral for ICA/FFR with more confidence.

Nucleon Energy Correlators for the Color Glass Condensate.

We demonstrate the recently proposed nucleon energy-energy correlator (NEEC) f_{EEC}(x,θ) can unveil the gluon saturation in the small-x regime in eA collisions. The novelty of this probe is that it is fully inclusive just like the deep-inelastic scattering (DIS), with no requirements of jets or hadrons but still provides an evident portal to the small-x dynamics through the shape of the θ distribution. We find that the saturation prediction is significantly different from the expectation of the collinear factorization.

Optimized O(α_{s}

The failure of observing the e^{+}e^{-}→J/ψJ/ψ events at B factories to date is often attributed to the significant negative order-α_{s} correction. In this work we compute the O(α_{s}^{2}) correction to this process for the first time. The magnitude of the next-to-next-to-leading order (NNLO) perturbative correction is substantially negative so that the standard nonrelativistic QCD prediction would suffer from an unphysical, negative cross section. This dilemma may be traced in the fact that the bulk contribution of the fixed-order radiative corrections stems from the perturbative corrections to the J/ψ decay constant. We thus implement an improved nonrelativistic QCD factorization framework, by decomposing the amplitude into the photon-fragmentation piece and the nonfragmentation piece. With the measured J/ψ decay constant as input, which amounts to resumming a specific class of radiative and relativistic corrections to all orders, the fragmentation-induced production rate can be predicted accurately and serves a benchmark prediction. The nonfragmentation type of the amplitude is then computed through NNLO in α_{s} and at lowest order in velocity. Both the O(α_{s}) and O(α_{s}^{2}) corrections in the interference term become positive and exhibit a decent convergence behavior. Our finest prediction is σ(e^{+}e^{-}→J/ψJ/ψ)=2.13_{-0.06}^{+0.30} fb at sqrt[s]=10.58 GeV. With the projected integrated luminosity of 50 ab^{-1}, the prospect to observe this exclusive process at Belle 2 experiment appears to be bright.

Association between BRCA mutations and endometrial carcinoma: a systematic review with meta-analysis.

PURPOSE: To first investigate on the association between BRCA mutations and endometrial carcinoma. To first evaluate the contribution of tamoxifen use and risk-reducing bilateral salping-oophenrectomy (BSO) on endometrial carcinoma in BRCA carriers. METHODS: A systematic search of electronic databases including the PubMed and EMBASE was conducted to identify publications exploring the association between BRCA mutations and endometrial carcinoma. Finally, single rate meta-analysis and diagnostic meta-analysis were performed. RESULTS: 11 retrospective studies and 3 prospective studies were included in the meta-analysis, single rate meta-analysis was performed on retrospective studies and prospective studies respectively. We got that incidence of BRCA mutations in patients with endometrial carcinoma is about 0.035, the incidence of endometrial carcinoma in BRCA carriers is about 0.004. Diagnostic meta-analysis performed on prospective studies found that tamoxifen increased incidence of endometrial carcinoma in BRCA carriers. CONCLUSIONS: The incidence of BRCA mutations in patients with endometrial carcinoma is about 0.035 according to present studies, the incidence of endometrial carcinoma in BRCA carriers is about 0.004. Tamoxifen use is a certain risk factor for subsequent endometrial carcinoma, while history of breast cancer or risk-reducing BSO is not associated with incidence of follow-up endometrial carcinoma. The necessity and rationality of prophylactic hysterectomy for BRCA carriers remained to be discussed.

The value of myocardial work in the estimation of left ventricular systolic function in patients with coronary microvascular disease: A study based on adenosine stress echocardiography.

Background: Coronary microvascular dysfunction (CMD) is associated with increased cardiovascular events in patients with angina with non-obstructive coronary (ANOCA), especially heart failure. Conventional echocardiography is difficult to identify early alterations in cardiac function due to CMD. Methods: We recruited 78 ANOCA patients. All patients underwent conventional echocardiography examination, adenosine stress echocardiography and examination of coronary flow reserve (CFR) by transthoracic echocardiography. Based on the CFR results, patients were divided into the CMD group (CFR < 2.5) and the non-CMD group (CFVR ≥ 2.5). Demographic data, conventional echocardiographic parameters, two-dimensional speckle-tracking echocardiography (2D-STE) parameters and myocardial work (MW) were compared between the two groups at rest and at stress. Logistic regression was used to analyze the factors associated with CMD. Results: There was no significant difference in conventional echocardiography parameters, 2D-STE related indices or MW at rest between the two groups. Global work index (GWI), global contractive work (GCW), and global work efficiency (GWE) were lower in the CMD group than in the non-CMD group at stress (p = 0.040, 0.044, <0.001, respectively), but global waste work (GWW) and peak strain dispersion (PSD) were higher (both p < 0.001). GWI and GCW were associated with systolic blood pressure, diastolic blood pressure, product of heart rate and blood pressure, GLS and coronary flow velocity. While GWW was mainly correlated with PSD, GWE was correlated with PSD and GLS. In the non-CMD group, the responses to adenosine was mainly manifested as an increase in GWI, GCW and GWE (p = 0.001, 0.001, 0.009, respectively) and a decrease in PSD and GWW (p = 0.001, 0.015, respectively). In the CMD group, the response to adenosine was mainly manifested as an increase in GWW and a decrease in GWE (p = 0.002, and 0.006, respectively). In the multivariate regression analysis, we found that ΔGWW (difference in GWW before vs. after adenosine stress) and ΔPSD (difference in PSD before vs. after adenosine stress) were independent factors associated with CMD. The ROC curves showed that the composite prediction model consisting of ΔGWW and ΔPSD had excellent diagnostic value for CMD (area under the curve = 0.913). Conclusion: In the present study, we found that CMD caused deterioration of myocardial work in ANOCA patients under adenosine stress, and that increased cardiac contraction asynchrony and wasted work may be the main changes caused by CMD.

Association between resting myocardial work indices and stress myocardial perfusion in patients with angina and non-obstructive coronary artery disease.

Background: Myocardial work (MW) indices and longitudinal strain (LS) are sensitive markers of early left ventricular systolic dysfunction. Stress computed tomography myocardial perfusion imaging (CT-MPI) can assess early myocardial ischemia. The association between resting MW indices and stress myocardial perfusion remains unclear. This study compares resting MW indices with LS to assess stress myocardial perfusion in angina patients with non-obstructive coronary artery disease (CAD). Methods: Eighty-four patients who underwent resting echocardiography, coronary computed tomography angiography, and stress CT-MPI were reviewed. Seventeen myocardial segments were divided into three regions according to the epicardial coronary arteries. Global indices included global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE). Regional indices included regional longitudinal strain (RLS), regional work index (RWI), and regional work efficiency (RWE). Reduced global perfusion was defined as an average stress myocardial blood flow (MBF) <116 mL/100 mL/min for the whole heart. Reduced regional perfusion was defined as an average stress MBF <116 mL/100 mL/min for the coronary territories. No patients demonstrated obstructions in the epicardial coronary arteries (stenosis diameter <50%). The MW indices and LS were compared. Receiver operating characteristic curves were constructed and logistic regression analyses were used to investigate the predictors of reduced myocardial perfusion. Results: Patients with reduced stress perfusion demonstrated reduced GLS, GWI, GCW, and GWE (P<0.05) and increased GWW (P<0.05). After adjustment for age and sex, GWE was still independently associated with reduced myocardial perfusion (odds ratio =0.386, 95% confidence interval: 0.214-0.697; P<0.05). Receiver operating characteristic curves reflected the good diagnostic ability of GWE and its superiority to GLS (area under the curve: 0.858 vs. 0.741). The optimal cutoff GWE value was 95% (sensitivity, 70%; specificity, 90%). Regions with lower stress perfusion showed lower RLS, RWI, and RWE (P<0.05). The optimal cutoff value of RWE for predicting reduced regional perfusion was 95%, with an area under the curve of 0.780, a sensitivity of 62%, and a specificity of 83%. Conclusions: Resting MW indices perform well in assessing global and regional stress myocardial perfusion in angina patients with non-obstructive CAD, and GWE is superior to GLS in the global evaluations.

Knowledge of Hyperemic Myocardial Blood Flow in Healthy Subjects Helps Identify Myocardial Ischemia in Patients With Coronary Artery Disease.

BACKGROUNDS: Dynamic CT myocardial perfusion imaging (CT-MPI) allows absolute quantification of myocardial blood flow (MBF). Although appealing, CT-MPI has not yet been widely applied in clinical practice, partly due to our relatively limited knowledge of CT-MPI. Knowledge of distribution and variability of MBF in healthy subjects helps in recognition of physiological and pathological states of coronary artery disease (CAD). OBJECTIVES: To describe the distribution and normal range of hyperemic MBF in healthy subjects obtained by dynamic CT-MPI and validate whether it can accurately identify functional myocardial ischemia when the cut-off value of hyperemia MBF is set to the lower limit of the normal range. MATERIALS AND METHODS: Fifty-one healthy volunteers (age, 38 ± 12 years; 15 men) were prospectively recruited. Eighty patients (age, 58 ± 10 years; 55 men) with suspected or known CAD who underwent interventional coronary angiography (ICA) examinations were retrospectively recruited. Comprehensive CCTA + dynamic CT-MPI protocol was performed by the third - generation dual-source CT scanner. Invasive fractional flow reserve (FFR) measurements were performed in vessels with 30-90% diameter reduction. ICA/FFR was used as the reference standard for diagnosing functional ischemia. The normal range for the hyperemic MBF were defined as the mean ± 1.96 SD. The cut-off value of hyperemic MBF was set to the lower limit of the normal range. RESULTS: The global hyperemic MBF were 164 ± 24 ml/100 ml/min and 123 ± 26 ml/100 ml/min for healthy participants and patients. The normal range of the hyperemic MBF was 116-211 ml/100 ml/min. Of vessels with an ICA/FFR result (n = 198), 67 (34%) were functionally significant. In the per-vessel analysis, an MBF cutoff value of <116 ml/100 ml/min can identify myocardial ischemia with a diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 85.9% (170/198), 91.0% (61/67), 83.2 % (109/131), 73.5% (61/83), and 94.8% (109/115). CT-MPI showed good consistency with ICA/FFR in diagnosing functional ischemia, with a Cohen's kappa statistic of 0.7016 (95%CI, 0.6009 - 0.8023). CONCLUSION: Recognizing hyperemic MBF in healthy subjects helps better understand myocardial ischemia in CAD patients.

Identification of Flow-Limiting Coronary Stenosis With PCS: A New Cost-Effective Index Derived From the Product of Corrected TIMI Frame Count and Percent Diameter Stenosis.

Background: Identifying functional coronary stenosis with simple and cost-effective methods during invasive coronary angiography is still challenging. Corrected TIMI frame count (CTFC) is considered to be the frame count velocity of coronary blood flow. We aimed to propose a simple and cost-effective index based on CTFC and percent diameter stenosis (DS) to identify flow-limiting coronary stenosis. For this, a new index was put forward as the product of CTFC and DS (PCS). PCS can be regarded as the loss of coronary blood flow due to diameter stenosis. Methods: DS, CTFC, PCS, and Fractional flow reserve (FFR) of 111 vessels in 84 patients with suspected coronary heart disease were measured. FFR ≤0.80 was defined as flow-limiting. Models involving CTFC, DS, and PCS were developed. Logistic regression was performed to evaluate the values on diagnosing flow-limiting stenosis. Results: Vessels with flow-limiting coronary stenosis exhibited higher CTFC values than those without (28.56 vs. 21.64). The performance including the AUC (0.887), sensitivity (87.8%), and Youden index (0.678) for detecting flow-limiting stenosis was improved by adding the CTFC to the DS, while PCS had the largest positive predictive value (PPV) and diagnostic accuracy (DA) being 72.0 and 82.9%, respectively. For vessels with ≥50% lesions, PCS still had the best DA (80.9%), specificity (85.9%), and PPV (72.9%). At the same stenosis severity level, the AUC, Youden index and, DA of PCS were higher than those of CTFC. Conclusions: PCS is simple and accurate to identify flow-limiting coronary stenosis, especially at vessels with moderate to severe stenosis.