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Coronary disease complexity is commonly used to guide revascularization strategy in patients with multivessel disease (MVD). The aim of this study was to assess the interactive effects of coronary complexity on percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) outcomes and identify the optimal threshold at which PCI can be considered a reasonable option. A total of 1,444 of 1,500 patients with MVD from the FAME (Fractional Flow Reserve versus Angiography for Multi-vessel Evaluation) 3 randomized trial were included in the analysis (710 CABG vs 734 PCI). SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) scores were transformed into restricted cubic splines, and logistic regression models were fitted, with multiplicative interaction terms for revascularization strategy. Optimal thresholds at which PCI is a reasonable alternative to CABG were determined on the basis of Cox regression model performance. The mean SYNTAX score (SS) was 25.9 ± 7.1. SS was associated with 1-year major adverse cardiac and cerebrovascular events among PCI patients and 3-year death, myocardial infarction, and stroke among CABG patients. Significant interactions were present between revascularization strategy and SS for 1- and 3-year composite endpoints (P for interaction <0.05 for all). In Cox regression models, outcomes were comparable between CABG and PCI for the 3-year primary endpoint for SS ≤24 (P = 0.332), with 44% of patients below this threshold and 32% below the conventional SS threshold of ≤22. In patients with MVD without left main disease, PCI and CABG outcomes remain comparable up to SS values in the mid- rather than low 20s, which allows the identification of a greater proportion of patients in whom PCI may be a reasonable alternative to CABG. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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. The distal reference lumen diameter by CCTA and OCT were 2.75 ​± ​0.53 ​mm and 2.72 ​± ​0.55 ​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%. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

To identify anatomical and morphological plaque features predictors of PCI and create a multiparametric score to increase the predictive yield. Moreover, we assessed the incremental predictive value of FFR CT (Fractional Flow Reserve derived from CCTA) trans -lesion gradient (ΔFFR CT) when integrated into the score. Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with FFR CT available, referred to invasive coronary angiogram and assessment of fractional flow reserve. Plaque analysis was performed using validated semi-automated software. Logistic regression was performed to identify anatomical and morphological plaque features predictive of PCI. Optimal thresholds were defined by area under the receiver-operating characteristics curve (AUC) analysis. A scoring system was developed in a derivation cohort (70 ​% of the study population) and tested in a validation cohort (30 ​% of patients). The overall study population included 340 patients (455 vessels), among which 238 patients (320 vessels) were included in the derivation cohort. At multivariate logistic regression analysis, absence of left main disease, diameter stenosis (DS), non-calcified plaque (NCP) volume, and percent atheroma volume (PAV) were independent predictors of PCI. Optimal thresholds were: DS ​≥ ​50 ​%, volume of NCP>113 ​mm3 and PAV>17 ​%. A weighted score (CT-PCI Score) ranging from 0 to 11 was obtained. The AUC of the score was 0.80 (95%CI 0.74–0.86). The integration of ΔFFR CT in the CT-PCI score led to a mild albeit not significant increase in the AUC (0.82, 95%CI 0.77–0.87, p ​= ​0.328). Plaque anatomy and morphology derived from CCTA could aid in identifying patients amenable to PCI. Derivation of the "CT-PCI score". At the top, each variable included in the score with the relative score assigned is described. At the bottom, the ROC curve of the score to predict PCI is reported. [Display omitted] Coronary CT Angiography (CCTA) has become an established tool in the diagnostic work-up of patients with a low-to-intermediate likelihood of coronary artery disease (CAD), allowing the evaluation of anatomical, morphological, and functional plaque features. CCTA could aid decision-making for treatment strategy. We derived a CCTA score (CT-PCI score) based on plaque anatomy and morphology able to predict PCI referral in a cohort of patients undergoing CCTA for suspected CAD, with FFR CT available, referred to invasive coronary angiography and physiological assessment. The AUC of the score was 0.80 (95%CI 0.74–0.86), sensitivity ​= ​68.0 ​%, specificity ​= ​84.0 ​%, accuracy ​= ​80.0 ​%. The integration of ΔFFR CT in the CT-PCI score led to a mild albeit not significant increase in the accuracy. [ABSTRACT FROM AUTHOR]

The interplay between coronary hemodynamics and plaque characteristics remains poorly understood. The aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics. This multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value. A total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87). Atherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688) [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] [ABSTRACT FROM AUTHOR]

The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD). This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG). The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG. The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively. By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate. [Display omitted] [ABSTRACT FROM AUTHOR]

Luminal stenosis, computed-tomography derived fractional-flow reserve (FFRCT), and high-risk plaque features on coronary computed tomography angiography (CCTA), are all known to be associated with adverse clinical outcomes. To assess the interactions between these variables, patient outcomes, and quantitative plaque volumes, have not been previously described. Patients with CCTAs (n=4,430) and one-year outcome data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry underwent AI enabled quantitative coronary plaque analysis. Optimal cutoffs for coronary total plaque volume (TPV) and each plaque subtype were derived using ROC analysis. The resulting plaque volumes were adjusted for age, sex, hypertension, smoking status, type 2 diabetes, hyperlipidemia, luminal stenosis, distal FFRCT, and translesional delta-FFRCT. Median plaque volumes and optimal cutoffs for these adjusted variables were compared with major adverse cardiac events (MACE), late revascularization, a composite of the two, and cardiovascular death & myocardial infarction (MI). At one-year, 55 patients (1.2%) had experienced MACE, and 123 (2.8%) had undergone late revascularization (>90 days). Following adjustment for age, sex, risk factors, stenosis and FFRCT, TPV above the ROC-derived optimal cutoff (TPV > 564 mm3) was associated with the MACE/late revascularization composite (adjusted HR 1.515, 95%CI 1.093-2.099, p=0.0126), and both components. Total percent atheroma volume greater than the optimal cutoff was associated with both MACE/late revascularization (TPAV >24.4%, HR 2.046, 95%CI 1.474-2.839, p<0.0001) and cardiovascular death/MI (TPAV >37.17%, HR 4.53, 95%CI 1.943-10.576, p=0.0005). Calcified, non-calcified and low-attenuation percentage atheroma volumes above the optimal cutoff were associated with all adverse outcomes, although this relationship was not maintained for cardiovascular death/MI in analyses stratified by median plaque volumes. Analysis of the ADVANCE registry using AI-enabled quantitative plaque analysis shows that total plaque volume is associated with one-year adverse clinical events, with incremental predictive value over luminal stenosis or abnormal physiology by FFRCT. [ABSTRACT FROM AUTHOR]

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An increase in fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with improvement in angina. Coronary artery disease (CAD) patterns (focal vs diffuse) influence the FFR change after stenting and may predict angina relief. The aim of this study was to investigate the differential improvement in patient-reported outcomes after PCI in focal and diffuse CAD as defined by the pullback pressure gradient (PPG). This is a subanalysis of the TARGET-FFR (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve) randomized clinical trial. The 7-item Seattle Angina Questionnaire (SAQ-7) was administered at baseline and 3 months after PCI. The PPG index was calculated from manual pre-PCI FFR pullbacks. The median PPG value was used to define focal and diffuse CAD. Residual angina was defined as an SAQ-7 score <100. A total of 103 patients were analyzed. There were no differences in the baseline characteristics between patients with focal and diffuse CAD. Focal disease had larger increases in FFR after PCI than patients with diffuse disease (0.30 ± 0.14 vs 0.19 ± 0.12; P < 0.001). Patients with focal disease who underwent PCI for focal CAD had significantly higher SAQ-7 summary scores at follow-up than those with diffuse CAD (87.1 ± 20.3 vs 75.6 ± 24.4; mean difference = 11.5 [95% CI: 2.8-20.3]; P = 0.01). After PCI, residual angina was present in 39.8% but was significantly less in those with treated focal CAD (27.5% vs 51.9%; P = 0.020). Residual angina after PCI was almost twice as common in patients with a low PPG (diffuse disease), whereas patients with a high PPG (focal disease) reported greater improvement in angina and quality of life. The baseline pattern of CAD can predict the likelihood of angina relief. (Trial of Angiography vs. pressure-Ratio-Guided Enhancement Techniques–Fractional Flow Reserve [TARGET-FFR]; NCT03259815) [Display omitted] [ABSTRACT FROM AUTHOR]

To investigate the learning curve and the minimum number of cases required for a cardiologist in training to acquire the skills to an accurate pre-TAVI cardiac CT (CCT) analysis using a semi-automatic software. In this prospective, observational study, 40 CCTs of patients scheduled for TAVI were independently evaluated twice by 5 readers (80 readings each, 400 in total): a certified TAVI-CT specialist served as the reference reader (RR) and 4 cardiology fellows (2 interventional and 2 non-invasive cardiac imaging) as readers. The primary outcome was the minimum number of cases required to achieve an accuracy in imaging interpretation ≥80%, defined as the agreement between each reader and the RR in both balloon and self-expandable valve size choice. The secondary outcomes were the intra- and inter-observer variability. After 50 readings (25 cases repeated twice) cardiology fellows were able to select the appropriate valve size with ≥ 80% of accuracy compared to the RR, independently of valve calcification, image quality and slice thickness. Learning curves of both interventional and non-invasive cardiac imaging fellows showed a similar trend. Cardiology fellows achieved a very high intra- and inter-observer reliability for both perimeter and area assessment, with an intraclass correlation coefficient (ICC) ranging from 0.96 to 0.99. Despite the individual differences, cardiology fellows required 50 readings (25 cases repeated twice) to get adequately skilled in the pre-TAVI CCT interpretation. These results provide valuable information for developing adequate training sessions and education protocols for both companies and cardiologists involved. We prospectively investigated the learning curve for a cardiologist in training to acquire the skills to an accurate pre-TAVI cardiac-CT (CCT) analysis, using a semi-automatic software. Forty CCTs of patients scheduled for TAVI were evaluated twice by 5 readers (80 readings each, 400 in total): a certified TAVI-CT specialist served as reference reader (RR) and 4 cardiology fellows as readers. After 50 readings (25 cases repeated twice) cardiology fellows were able to select the appropriate valve size with ≥80% of accuracy compared to RR. These results provide valuable information for developing adequate training sessions for companies and cardiologists involved. [Display omitted] [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) has become the most common pediatric liver disease. The intrauterine and early life environment can have an important impact on long-term metabolic health. We investigated the impact of maternal prepregnancy obesity, (pre)gestational diabetes, breastfeeding, and birth anthropometrics/preterm birth on the development of NAFLD in children and adolescents. A comprehensive search was performed in MEDLINE, PubMed Central, EMBASE, and grey literature databases through August 2020. The primary outcome was the prevalence of pediatric NAFLD, whereas the histologic severity of steatohepatitis and/or fibrosis were secondary outcomes. Study selection, data extraction, and quality assessment were performed by 2 independent reviewers. Our systematic review included 33 articles. Study heterogeneity regarding patient populations, diagnostic tools, and overall quality was considerable. Eight studies determined the impact of maternal prepregnancy overweight/obesity and identified this as a possible modifiable risk factor for pediatric NAFLD. Conversely, 8 studies investigated (pre)gestational diabetes, yet the evidence on its impact is conflicting. Breastfeeding was associated with a reduced risk for NAFLD, steatohepatitis, and fibrosis, especially in studies that evaluated longer periods of breastfeeding. Being born preterm or small for gestational age has an unclear impact on the development of NAFLD, although an early catch-up growth might drive NAFLD. In a systematic review, we found that maternal prepregnancy overweight and obesity were associated with an increased risk of pediatric NAFLD. Breastfeeding might be protective against the development of NAFLD when the duration of breastfeeding is sufficiently long (≥6 months). [Display omitted] [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the safety of selective intracoronary hypothermia during primary percutaneous coronary intervention (PPCI) in patients with anterior ST-segment elevation myocardial infarction (STEMI). Selective intracoronary hypothermia is a novel treatment designed to reduce myocardial reperfusion injury and is currently being investigated in the ongoing randomized controlled EURO-ICE (European Intracoronary Cooling Evaluation in Patients With ST-Elevation Myocardial Infarction) trial (NCT03447834). Data on the safety of such a procedure during PPCI are still limited. The first 50 patients with anterior STEMI treated with selective intracoronary hypothermia during PPCI were included in this analysis and compared for safety with the first 50 patients randomized to the control group undergoing standard PPCI. In-hospital mortality, occurrence of rhythm or conduction disturbances, stent thrombosis, onset of heart failure during the procedure, and subsequent hospital admission were assessed. In-hospital mortality was 0%. One patient in both groups developed cardiogenic shock. Atrial fibrillation occurred in 0 and 3 patients (P = 0.24), and ventricular fibrillation occurred in 5 and 3 patients (P = 0.72) in the intracoronary hypothermia group and control group, respectively. Stent thrombosis occurred in 2 patients in the intracoronary hypothermia group; 1 instance was intraprocedural, and the other occurred following interruption of dual-antiplatelet therapy consequent to an intracranial hemorrhage 6 days after enrollment. No stent thrombosis was observed in the control group (P = 0.50). Selective intracoronary hypothermia during PPCI in patients with anterior STEMI can be implemented within the routine of PPCI and seems to be safe. The final safety results will be reported at the end of the trial. [Display omitted] [ABSTRACT FROM AUTHOR]

Coronary computed tomography angiography (CCTA) is now an established tool in the diagnostic work-up of patients suspected to have coronary artery disease. Yet, its usefulness beyond this phase has not been fully explored. The current review focuses on the implementation of CCTA as a tool to plan and guide coronary interventions in the catheterization laboratory. Specifically, we explore the potential of CCTA to improve patient selection for percutaneous revascularization, provide the rationale for better resource use, and present a novel approach to incorporate 3-dimensional CT guidance for percutaneous coronary interventions. [Display omitted] • The role of CCTA for the diagnosis and stratification of CAD is well established; however, its usefulness beyond the diagnostic phase remains to be determined. • For patients referred to the cath lab, CCTA aids evaluating the likelihood of functional revascularization, adapting the cath lab resources to the case complexity, complementing conventional angiography based on the information of 3-dimensional model and by online real-time integration of CCTA data in the cath lab. • Online CT-guidance for coronary procedures has the potential to improve diagnostic and therapeutic intervention. • The clinical benefit of this CT-guided PCI warrants demonstration is a randomized trial. [ABSTRACT FROM AUTHOR]

The ADVANCE registry is a large prospective study of outcomes and resource utilization in patients undergoing coronary computed tomography angiography (CCTA) and CT-based fractional flow reserve (FFR CT). As experience with new technologies and practices develops over time, we investigated temporal changes in the use of FFR CT within the ADVANCE registry. 5083 patients with coronary artery disease (CAD) on CCTA were prospectively enrolled in the ADVANCE registry and were divided into 3 equally sized cohorts based on the temporal order of enrollment per site. Demographics, CCTA and FFR CT findings, and clinical outcomes through 1-year follow-up, were recorded and compared between tertiles. The number of patients with a ≥70% stenosis on CCTA was similar over time (33.6%, 30.9%, and 33.8% for cohort 1–3). The rate of positive FFR CT ≤0.80 was higher for cohorts 2 (67.3%) and 3 (74.6%) than for cohort 1 (57.1%, p < 0.001). Invasive FFR rates decreased from 25.8% to 22.4% between cohort 1 and 3 (p = 0.023). Moreover, patients with a FFR CT ≤0.80 were less frequently referred for invasive coronary angiography (ICA) (from 62.9% to 52.9%, p < 0.001), and underwent fewer revascularizations between cohort 1 and 3 (from 41.9% to 32.0%, p < 0.001). The prevalence of major events was low (1.2%) and similar between cohorts. Growing experience with FFR CT improved the likelihood of identifying hemodynamically significant CAD and safely reduced the need for ICA and revascularization in patients with anatomically significant disease even in the instance of an abnormal FFR CT. [ABSTRACT FROM AUTHOR]

This in vitro study sought to compare the efficacy of a sonic irrigant activation device with ultrasonic activation and needle irrigation in removing hard tissue debris (HTD) from anatomic complexities of the root canal system. Twenty-seven mesial roots of extracted human mandibular molars with 2 canals connected by an isthmus were selected based on micro–computed tomography scans (12-μm voxel size). The mesial canals were mechanically prepared to ProTaper Next X3 (Dentsply Maillefer, Ballaigues, Switzerland) and anatomically distributed into 3 groups (n = 9) according to the final irrigation protocol: sonically activated irrigation (SAI) using the EDDY system (VDW GbmH, Munich, Germany) for 3 × 20 seconds, ultrasonically activated irrigation (UAI) using a size 20 Irrisafe tip (Satelec Acteon, Mérignac, France) for 3 × 20 seconds, and conventional irrigation using a 30-G needle adapted to a syringe. Micro–computed tomographic scans were taken after instrumentation and after supplementary activation of the irrigant. After reconstruction and coregistration, the volume filled with HTD before and after irrigant activation was calculated, and the mean percentage of HTD reduction after final irrigation was compared within and among groups using the paired sample t test and 1-way analysis of variance post hoc Tukey test, respectively (α = 5%). A significant reduction in the volume filled with HTD after irrigant activation was observed in all groups (P <.05). The percentage reduction of HTD in the UAI group (66.8%) was significantly higher than that in the SAI group (36.4%) (P <.05), whereas the conventional irrigation group result (43.7%) did not differ statistically from the UAI or SAI groups (P >.05). All tested supplementary irrigation steps significantly reduced the amount of debris created during root canal preparation. Ultrasonic activation resulted in the highest mean debris reduction. [ABSTRACT FROM AUTHOR]

The identification of factors determining whether a lesion progresses, destabilizes or becomes quiescent remains a challenge. Wall or endothelial shear stress (WSS or ESS, respectively), the frictional force acting on the lumen wall, is strongly associated with changes in the natural history of lesions. Several clinical intravascular imaging studies have shown a clear link between disturbed flow, typically characterized by low WSS, and plaque growth. In support of these studies, in-vitro experiments of shear stress have identified several mechanisms promoting atherosclerosis. More recently, the relationship between WSS and major adverse cardiac events has been explored. Improvements in coronary computed tomography angiography (CCTA) image resolution and quality has allowed for the calculation of WSS from CT. In this review, we provide an introduction to WSS, highlight important human and animal intravascular-based WSS studies, and discuss CT-based WSS studies to date. Finally, we discuss future directions of CCTA and WSS computation. [ABSTRACT FROM AUTHOR]

Background: In ST-elevation myocardial infarction (STEMI) patients presenting with multivessel disease (MVD), recent studies have demonstrated the superiority of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for non-culprit lesions compared to culprit lesion treatment-only therapy. FFR- and angio-guided PCI have however never been compared in STEMI patients.Trial Design: FLOWER-MI is an open-label multicenter national randomized clinical trial. The aim is to investigate FFR-guided complete revascularization in comparison to angio-guided complete revascularization in STEMI patients with successful PCI of the culprit lesion and ≥50% stenosis in at least one additional non-culprit lesion requiring PCI. Eligible patients will be randomized after successful primary PCI in a 1:1 fashion to either FFR-guided or angio-guided complete revascularization during the index procedure or a staged procedure before discharge (≤5 days). Patients assigned to FFR guidance first have FFR measured in each non-culprit vessel and only undergo PCI if FFR is ≤0.80. The primary end point of the study is a composite of major adverse cardiac events, including all-cause death, non-fatal MI, and unplanned hospitalization leading to urgent revascularization at 1 year. Secondary end points will include the individual adverse events, cost-effectiveness, quality of life, and 30-day, 6-month, and 3-year outcomes. Based on estimated event rates, a sample size of 1170 patients is needed to show superiority of the FFR-guided revascularization with 80% power.Conclusion: The aim of FLOWER-MI trial is to assess whether FFR-guided complete revascularization in the acute setting is superior angio-guided complete revascularization. [ABSTRACT FROM AUTHOR]

Fractional flow reserve (FFR) pullback allows to assess the distribution of pressure loss along the coronary vessels. FFR derived from CT (FFR CT) provides a virtual pullback curve that may also aid in the assessment of the distribution of epicardial coronary resistance in the non-invasive setting. The present study aims to determine the accuracy of the virtual FFR CT pullback curve using a motorized invasive FFR pullback as reference in patients with stable coronary artery disease. FFR values were extracted from coronary vessels at approximately 1 mm to generate pullback curves. Invasive motorized FFR pullbacks were acquired using a dedicated device at a speed of 1 mm/s. A total of 3172 matched FFR CT and FFR values were obtained in 24 vessels. The correlation coefficient between FFR CT and FFR was 0.76 (95%CI 0.75 to 0.78; p < 0.001). The area under the pullback curve was similar between FFR CT and invasive FFR (79.0 ± 16.1 vs. 85.3 ± 16.4, p = 0.097). The mean difference in lesion gradient between FFR CT and FFR was −0.07 (LOA -0.26 to 0.13) whereas in non-obstructive segments was −0.01 (LOA -0.06 to 0.05). The evaluation of epicardial coronary resistance using coronary CT angiography with FFR CT was feasible. FFR CT virtual pullback appears to be accurate for the evaluation of pressure gradients. FFR CT has the potential to identify the pathophysiological pattern of coronary artery disease in the non-invasive setting. [ABSTRACT FROM AUTHOR]

This study sought to assess the diagnostic performance of FFRangio (CathWorks, Kfar Saba, Israel), an angiogram-derived fractional flow reserve (FFR) technology. Despite practice guidelines recommendations, the use of coronary physiologic assessment in daily practice remains low for patients undergoing coronary angiography. Angiogram-derived FFR technologies have the potential to promote the integration of physiologic assessment in daily practice. The study performed an analysis of pooled patient- and lesion-level data from 5 prospective cohort studies that examined the diagnostic performance of FFRangio compared with the reference standard wire-based FFR. A total of 700 lesions from 588 patients were analyzed. Mean age was 65 years, 71% were men, and 40% presented with acute coronary syndromes. Mean FFR and FFRangio were 0.81 ± 0.12 and 0.81 ± 0.11, with 31.6% and 31.4% of lesions were in the 0.75 to 0.85 range, respectively. When using a binary cutoff FFR value of 0.80, FFRangio showed a sensitivity of 91%, a specificity of 94%, and a diagnostic accuracy of 93%. The mean difference between FFR and FFRangio was 0.00 ± 0.12. The correlation coefficient between FFR and FFRangio was 0.83 (p < 0.001). The C-statistic for FFRangio was 0.95 (p < 0.001). The accuracy of FFRangio was consistent across all subgroups examined. In the largest reported cohort examining the performance of angiogram-derived FFR technology, FFRangio showed excellent diagnostic performance, which was robust and consistent across all patient and lesion subgroups. Additional studies are needed allow FFRangio and fulfill its potential expand the implementation of functional assessment of coronary lesions in routine clinical practice. [ABSTRACT FROM AUTHOR]

The 1-year data from the international ADVANCE (Assessing Diagnostic Value of Non-invasive FFR CT in Coronary Care) Registry of patients undergoing coronary computed tomography angiography (CTA) was used to evaluate the relationship of fractional flow reserve derived from coronary CTA (FFR CT) with downstream care and clinical outcomes. Guidelines for management of chest pain using noninvasive imaging pathways are based on short- to intermediate-term outcomes. Patients (N = 5,083) evaluated for clinically suspected coronary artery disease and in whom atherosclerosis was identified by coronary CTA were prospectively enrolled at 38 international sites from July 15, 2015, to October 20, 2017. Demographics, symptom status, coronary CTA and FFR CT findings and resultant site-based treatment plans, and clinical outcomes through 1 year were recorded and adjudicated by a blinded core laboratory. Major adverse cardiac events (MACE), death, myocardial infarction (MI), and acute coronary syndrome leading to urgent revascularization were captured. At 1 year, 449 patients did not have follow-up data. Revascularization occurred in 1,208 (38.40%) patients with an FFR CT ≤0.80 and in 89 (5.60%) with an FFR CT >0.80 (relative risk [RR]: 6.87; 95% confidence interval [CI]: 5.59 to 8.45; p < 0.001). MACE occurred in 55 patients, 43 events occurred in patients with an FFR CT ≤0.80 and 12 occurred in those with an FFR CT >0.80 (RR: 1.81; 95% CI: 0.96 to 3.43; p = 0.06). Time to first event (all-cause death or MI) occurred in 38 (1.20%) patients with an FFR CT ≤0.80 compared with 10 (0.60%) patients with an FFR CT >0.80 (RR: 1.92; 95% CI: 0.96 to 3.85; p = 0.06). Time to first event (cardiovascular death or MI) occurred cardiovascular death or MI occurred more in patients with an FFR CT ≤0.80 compared with patients with an FFR CT >0.80 (25 [0.80%] vs. 3 [0.20%]; RR: 4.22; 95% CI: 1.28 to 13.95; p = 0.01). The 1-year outcomes from the ADVANCE FFR CT Registry show low rates of events in all patients, with less revascularization and a trend toward lower MACE and significantly lower cardiovascular death or MI in patients with a negative FFR CT compared with patients with abnormal FFR CT values. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Wave [ADVANCE]; NCT02499679) [ABSTRACT FROM AUTHOR]

Abstract Objectives The aim of this study was to investigate the impact of pre-diabetes (pre-DM) on coronary plaque characteristics and ischemic outcomes in patients with acute coronary syndromes (ACS). Background Pre-DM (i.e., the early stages of glucometabolic disturbance) is common among patients with ACS, but the extent to which pre-DM influences coronary plaque characteristics and the risk for adverse ischemic events is unclear. Methods In the PROSPECT (Providing Regional Observations to Study Predictors of Events in Coronary Tree) study, patients with ACS underwent quantitative coronary angiography, grayscale intravascular ultrasound, and radiofrequency intravascular ultrasound after successful percutaneous coronary intervention. Patients were divided into 3 groups according to their glucometabolic status, as defined by the American Diabetes Association: normal glucose metabolism (NGM), pre-DM, and diabetes mellitus (DM). These groups were compared with regard to coronary plaque characteristics and the risk for major adverse cardiac events (MACEs) (defined as cardiac death or arrest, myocardial infarction, or rehospitalization for unstable or progressive angina). Results Among 547 patients, 162 (29.6%) had NGM, 202 (36.9%) had pre-DM, and 183 (33.4%) had DM. There were no significant differences between the groups with regard to intravascular ultrasound findings indicative of vulnerable plaques. Patients with DM had a higher crude rate of MACEs than those with pre-DM or NGM (25.9% vs. 16.3% and 16.1%; p = 0.03 and p = 0.02, respectively). In an adjusted Cox regression model using NGM as the reference group, DM (hazard ratio: 2.20; 95% confidence interval: 1.25 to 3.86; p = 0.006) but not pre-DM (hazard ratio: 1.29; 95% confidence interval: 0.71 to 2.33; p = 0.41) was associated with increased risk for MACEs. Conclusions Impaired glucose metabolism is common among patients presenting with ACS. DM but not pre-DM is associated with an increased risk for MACEs. Thus, preventing patients from progressing from pre-DM to DM is important. (PROSPECT: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466) Graphical abstract [ABSTRACT FROM AUTHOR]

Abstract Introduction The purpose of this study was to compare in vitro the canal and isthmus debridement of manual-dynamic, passive ultrasonic, and laser-activated irrigation with an Er:YAG laser in mesial roots of human mandibular molars. Methods Fifty extracted mandibular molars with an isthmus were embedded in resin and sectioned axially 4 mm from the apex. The teeth were reassembled with guide pins and bolts, and the mesial canals were instrumented up to a ProTaper F2 rotary file (Dentsply Maillefer, Ballaigues, Switzerland). Teeth were randomly assigned to the following irrigant activation groups (n = 10): conventional needle irrigation (NI), manual-dynamic irrigation with a ProTaper F2 gutta-percha cone, ultrasonically activated irrigation using a size 20 Irrisafe (Satelec Acteon, Mérignac, France), and laser-activated irrigation (LAI) with an Er:YAG laser and a conical 400-μm fiber tip in the canal entrance or a 600-μm tip over the canal entrance. Root cross-sectional images were taken before and after final irrigation, and the area occupied by debris in the main canal and the isthmus was determined using image analysis software. Differences in debris before and after activation were statistically compared within and across groups. Results Significant reductions in debris levels were observed in all groups, except for NI and manual-dynamic irrigation (canal only). None of the methods rendered the canal systems debris free. In the canal, LAI with an Er:YAG laser and a 600-μm tip over the canal entrance removed significantly more debris than NI. In the isthmus, LAI with an Er:YAG laser and a conical 400-μm fiber tip in the canal entrance removed significantly more debris than NI. Conclusions Within the limitations of this in vitro study, canal and isthmus cleanliness significantly improved after irrigant activation. Highlights • A modified K-Kube model was used to investigate canal system debridement of different irrigant activation methods. • Canal system cleanliness significantly improved with all activation methods. • Laser-activated irrigation regimens resulted in the highest debris reductions, but they were not significantly different from the other groups. [ABSTRACT FROM AUTHOR]

Objectives The goal of this study was to investigate sex differences in adenosine-free coronary pressure indexes. Background Several adenosine-free coronary pressure wire indexes have been proposed to assess the functional significance of coronary artery lesions; however, there is a theoretical concern that sex differences may affect diagnostic performance because of differences in resting flow and distal myocardial mass. Methods In this CONTRAST (Can Contrast Injection Better Approximate FFR Compared to Pure Resting Physiology?) substudy, contrast fractional flow reserve (cFFR), obtained during contrast-induced submaximal hyperemia, the instantaneous wave-free ratio (iFR), and distal/proximal coronary pressure ratio (Pd/Pa) were compared with fractional flow reserve (FFR) in 547 men and 216 women. Using FFR ≤0.8 as a reference, the diagnostic performance of each index was compared. Results Men and women had similar diameter stenosis (p = 0.78), but women were less likely to have FFR ≤0.80 than men (42.5% vs. 51.5%, p = 0.04). Sensitivity was similar among cFFR, iFR, and Pd/Pa when comparing women and men, respectively (cFFR, 77.5% vs. 75.3%; p = 0.69; iFR, 84.9% vs. 79.4%; p = 0.30; Pd/Pa, 78.8% vs. 77.3%; p = 0.78). cFFR was more specific than iFR or Pd/Pa regardless of sex (cFFR, 94.3% vs. 95.8%; p = 0.56; iFR, 75.6% vs. 80.1%; p = 0.38; Pd/Pa, 80.6% vs. 78.7%; p = 0.69). By receiver-operating characteristic curve analysis, cFFR provided better diagnostic accuracy than resting indexes irrespective of sex (p ≤ 0.0001). Conclusions Despite the theoretical concern, the diagnostic sensitivity and specificity of cFFR, iFR, and Pd/Pa did not differ between the sexes. Irrespective of sex, cFFR provides the best diagnostic performance. [ABSTRACT FROM AUTHOR]

Objectives The aims of the present study were: 1) to investigate the contribution of the extent of luminal stenosis and other lesion composition-related factors in predicting invasive fractional flow reserve (FFR); and 2) to explore the distribution of various combinations of morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR. Background In patients with stable ischemic heart disease, FFR-guided revascularization, as compared with medical therapy alone, is reported to improve outcomes. Because morphological characteristics are the basis of plaque rupture and acute coronary events, a relationship between FFR and lesion characteristics may exist. Methods This is a subanalysis of NXT (HeartFlowNXT: HeartFlow Analysis of Coronary Blood Flow Using Coronary CT Angiography), a prospective, multicenter study of 254 patients (age 64 ± 10 years, 64% male) with suspected stable ischemic heart disease; coronary computed tomography angiography including plaque morphology assessment, invasive angiography, and FFR were obtained for 383 lesions. Ischemia was defined by invasive FFR ≤0.80. Computed tomography angiography–defined morphological characteristics of plaques and their vascular location were used in univariate and multivariate analyses to examine their predictive value for invasive FFR. The distribution of various combinations of plaque morphological characteristics and the severity of stenosis among lesions demonstrating normal and abnormal FFR were examined. Results The percentage of luminal stenosis, low-attenuation plaque (LAP) or necrotic core volume, left anterior descending coronary artery territory, and the presence of multiple lesions per vessel were the predictors of FFR. When grouped on the basis of degree of luminal stenosis, FFR-negative lesions had consistently smaller LAP volumes compared with FFR-positive lesions. The distribution of plaque characteristics in lesions with normal and abnormal FFR demonstrated that whereas FFR-negative lesions excluded likelihood of stenotic plaques with moderate to high LAP volumes, only one-third of FFR-positive lesions demonstrated obstructive plaques with moderate to high LAP volumes. Conclusions In addition to the severity of luminal stenosis, necrotic core volume is an independent predictor of FFR. The distribution of plaque characteristics among lesions with varying luminal stenosis and normal and abnormal FFR may explain the outcomes associated with FFR-guided therapy. [ABSTRACT FROM AUTHOR]

Background To date, the clinical utility of coronary computed tomography angiography (CTA)-derived fractional flow reserve (FFRCT) has been limited to trials and single center experiences. We herein report the incidence of abnormal FFRCT (≤0.80) and the relationship of lesion-specific ischemia to subject demographics, symptoms, and degree of stenosis in the multicenter, prospective ADVANCE registry. Methods One thousand patients with suspected angina having documented coronary artery disease on coronary CTA and clinically referred for FFR CT were prospectively enrolled in the registry. Patient demographics, symptom status, coronary CTA and FFR CT findings were recorded. Univariate and multivariate analyses were performed to investigate the predictors related to abnormal FFR CT . Results FFR CT data were analyzed in 952 patients (95.2%). Overall, 51.1% patients had a positive FFR CT value (≤0.80). Patients with ≥3 risk factors had a significantly higher rate of abnormal FFR CT than those with <3 risk factors (60.2% vs. 43.9%, p = 0.0001). On multivariate analysis, baseline diabetes (odds ratio [OR] 1.52, 95% confidence interval [CI] 1.04–2.21, p = 0.030) and hypertension (OR 1.56, 95%CI 1.14–2.14, p = 0.005) were both predictive of abnormal FFR CT . In addition, >70% stenosis was significantly associated with low FFR CT (OR 31.16, 95%CI 12.25–79.22, p < 0.0001) vs. <30% stenosis. Notably, stenosis 30–49% vs. <30% had an increased likelihood of ischemia (OR 3.74, 95%CI 1.52–9.17, p < 0.0001). Conclusions In this real-world registry, CT angiographic stenosis severity in addition to baseline cardiovascular risk factors conferred an increased likelihood of an abnormal FFR CT . Importantly, however, mild CT angiographic stenoses were noted to have an increased hazard for ischemia and the converse holding true for more severe stenoses as well. [ABSTRACT FROM AUTHOR]

To investigate the technical outcome, clinical outcome, and patency of transjugular intrahepatic portosystemic shunt (TIPS) in pediatric portal hypertension (PHT). A systematic search of MEDLINE/PubMed, EMBASE, Cochrane databases, ClinicalTrials.gov , and WHO ICTRP registries was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. An a priori protocol was registered at the PROSPERO database. Original full-text articles on pediatric patients (sample size of ≥5 patients with upper age limit of 21 years) with PHT who underwent TIPS creation for any indication were included. Seventeen studies with 284 patients (average-weighted age of 10.1 years) were included, with an average-weighted follow-up of 3.6 years. TIPS was technically successful in 93.3% (95% confidence interval [CI], 88.5%–97.1%) of patients, with a major adverse event rate of 3.2% (95% CI, 0.7–6.9) and adjusted hepatic encephalopathy rate of 2.9% (95% CI, 0.6–6.3). The pooled 2-year primary and secondary patency rates were 61.8% (95% CI, 50.0–72.4) and 99.8% (95% CI, 96.2%–100.0%), respectively. Stent type (P =.002) and age (P =.04) were identified as a significant source of heterogeneity for clinical success. In subgroup analysis, the clinical success rate was 85.9% (95% CI, 77.8–91.4) in studies with a majority of covered stents, and 87.6% (95% CI, 74.1–94.6) in studies with a median age of 12 years or older. This systematic review and meta-analysis demonstrates that a TIPS is a feasible and safe treatment for pediatric PHT. To improve clinical outcome and patency on the long term, the use of covered stents should be encouraged. [Display omitted] [ABSTRACT FROM AUTHOR]

Summary The evidence for organic pathogenetic factors in enuresis and the discovery of effective therapies targeting the bladder and/or nocturnal diuresis have overwhelmed every potential role of psychological factors in pathogenesis and treatment. However, psychopathology is still important in enuresis because according to the document of the International Children's Continence Society (ICCS) 20–30% of the children with enuresis have at least one psychological/psychiatric disorder at rates two times higher than non-wetting children. The most common comorbid disorder with enuresis is attention deficit hyperactivity disorder. The aim of this review is to translate the existing evidence on the importance of a psychological screening into daily clinical practice of the medical practitioner. The use of the minimal psychological screening tool should be considered mandatory in each primary setting. If psychological problems are indicated, referral of the patient to a multidisciplinary setting should be considered, not only to allow psychological assessment to screen for a possible psychopathology, but also since therapy resistance might be expected. This review concentrates on two items from psychopathology/psychotherapy that might predict insufficient treatment response: the psychological comorbidities as described according to the DSM-5 criteria and the underestimated importance of therapy adherence. Adherence is a cornerstone of effective therapy in enuresis. It is a problem involving the doctor, the patient, and the parents. Increasing adherence takes effort and is time-consuming. But it is worthwhile knowing that several studies have demonstrated that high adherence is associated with high therapy success of enuresis. Eventually, this is the ultimate goal of treatment. [ABSTRACT FROM AUTHOR]