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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]

BACKGROUND: Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF). METHODS: Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery--related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery--related mass. RESULTS: Patients with HFrEF showed a higher left ventricular and left anterior descending artery--related myocardial mass compared with HF with preserved ejection fraction (P<0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P=0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P≤0.030). CONCLUSIONS: Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up. [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]

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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]

Background: We evaluate the prognostic value of measuring fractional flow reserve (FFR) after percutaneous coronary intervention (post-PCI FFR) and intravascular imaging in patients undergoing PCI for 3-vessel coronary artery disease in the FAME 3 trial (Fractional Flow Reserve versus Angiography for Multivessel Evaluation). Methods: The FAME 3 trial is a multicenter, international, randomized study comparing FFR-guided PCI with coronary artery bypass grafting in patients with multivessel coronary artery disease. PCI was not noninferior with respect to the primary end point of death, myocardial infarction, stroke, or repeat revascularization at 1 year. Post-PCI FFR data were acquired on a patient and vessel-related basis. Intravascular imaging guidance was tracked. The primary end point is a comparison of target vessel failure (TVF) defined as a composite of cardiac death, target vessel myocardial infarction, and target vessel revascularization at 1 year based on post-PCI FFR values. Cox regression with robust SEs was used for analysis. Results: Of the 757 patients randomized to PCI, 461 (61%) had post-PCI FFR measurement and 11.1% had intravascular imaging performed. The median post-PCI FFR was 0.89 [IQR‚ 0.85–0.94]. On a vessel-level, post-PCI FFR was found to be a significant predictor of TVF univariately (hazard ratio=0.67 [95% CI‚ 0.48–0.93] for 0.1 unit increase, P =0.0165). On a patient-level, the single lowest post-PCI FFR value was also found to be a significant predictor of TVF univariately (hazard ratio=0.65 [95% CI‚ 0.48–0.89] for 0.1 unit increase, P =0.0074). Post-PCI FFR was an independent predictor of TVF in multivariable analysis adjusted for key clinical parameters. Outcomes were similar between patients who had intravascular imaging guidance and those who did not. Conclusions: Post-PCI FFR measurement was a significant predictor of TVF on a vessel and patient level and an independent predictor of outcomes in a population with complex 3-vessel coronary artery disease eligible for coronary artery bypass grafting. The limited use of intravascular imaging did not affect outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02100722. [ABSTRACT FROM AUTHOR]

Background: Hemodynamic assessment of untreated nonculprit lesions was not studied in the PROSPECT study (Providing Regional Observations to Study Predictors of Events in the Coronary Tree). We developed a virtual intravascular ultrasound–derived lesion-specific fractional flow reserve (lesion-specific IVUS-FFR) algorithm to assess individual lesion-level FFR. We sought to investigate the relation between lesion-specific IVUS-FFR and major adverse cardiovascular events (MACE) arising from untreated nonculprit lesions in the PROSPECT study. Methods: In PROSPECT, 697 patients with acute coronary syndromes underwent 3-vessel grayscale and virtual histology–IVUS to correlate untreated nonculprit plaque morphology with 3-year nonculprit related MACE (composite of cardiac death, cardiac arrest, myocardial infarction, or rehospitalization due to unstable or progressive angina). Lesion-specific IVUS-FFR was calculated from volumetric IVUS lumen area measurements at 0.4 mm intervals by applying a mathematical circulation model using basic fluid dynamics equations. Results: Lesion-specific IVUS-FFR was analyzable in 3227 nonculprit lesions in 660 patients among whom 54 nonculprit MACE events (3 myocardial infarctions) occurred at median 3.4-year follow-up. By receiver-operating characteristic analysis, the best cutoff value of lesion-specific IVUS-FFR to predict nonculprit MACE was ≤0.95. After adjusting for patient and lesion characteristics, lesion-specific IVUS-FFR (hazard ratio, 4.83 [95% CI, 2.20–10.61]; P <0.001) was an independent predictor of 3-year nonculprit MACE, in addition to minimum lumen area≤4.0 mm2, plaque burden ≥70%, and virtual histology thin-cap fibroatheroma. Conclusions: Minor reductions in lesion-specific IVUS-FFR were independently associated with future nonculprit MACE arising from untreated angiographically mild stenoses along with previously established high-risk lesion morphological characteristics. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00180466. [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]