Prognostic value of CAD-RADS classification by coronary CTA in patients with suspected CAD.

BACKGROUND: The study sought to compare Coronary Artery Disease Reporting and Data System (CAD-RADS) classification with traditional coronary artery disease (CAD) classifications and Duke Prognostic CAD Index for predicting the risk of all-cause mortality in patients with suspected CAD. METHODS: 9625 consecutive suspected CAD patients were assessed by coronary CTA for CAD-RADS classification, traditional CAD classifications and Duke Prognostic CAD Index. Kaplan-Meier and multivariable Cox models were used to estimate all-cause mortality. Discriminatory ability of classifications was assessed using time dependent receiver-operating characteristic (ROC) curves and The Hosmer-Lemeshow goodness-of-fit test was employed to evaluate calibration. RESULTS: A total of 540 patients died from all causes with a median follow-up of 4.3 ± 2.1 years. Kaplan-Meier survival curves showed the cumulative events increased significantly associated with CAD-RADS, three traditional CAD classifications and Duke Prognostic CAD Index. In multivariate Cox regressions, the risk for the all-cause death increased from HR 0.861 (95% CI 0.420-1.764) for CAD-RADS 1 to HR 2.761 (95% CI 1.961-3.887) for CAD-RADS 4B&5, using CAD-RADS 0 as the reference group. The relative HRs for all-cause death increased proportionally with the grades of the three traditional CAD classifications and Duke Prognostic CAD Index. The area under the time dependent ROC curve for prediction of all-cause death was 0.7917, 0.7805, 0.7991for CAD-RADS in 1 year, 3 year, 5 year, respectively, which was non-inferior to the traditional CAD classifications and Duke Prognostic CAD Index. CONCLUSIONS: The CAD-RADS classification provided important prognostic information for patients with suspected CAD with noninvasive evaluation, which was non-inferior than Duke Prognostic CAD Index and traditional stenosis-based grading schemes in prognostic value of all-cause mortality. Traditional and simplest CAD classification should be preferable, given the more number of groups and complexity of CAD-RADS and Duke prognostic index, without using more time consuming classification.

Determinants of Periprocedural Myocardial Infarction in Current Elective Percutaneous Coronary Interventions.

Periprocedural myocardial infarction (PMI) is closely associated with long-term cardiovascular events. The factors associated with PMI are not fully understood. The purpose of this study was to investigate the determinants of PMI in contemporary elective percutaneous coronary intervention (PCI). Overall, 731 elective PCI was divided into the PMI (n = 27) and non-PMI (n = 704) groups. Univariate and multivariate logistic regression analysis was used to find factors associated with PMI. In the univariate analysis, PMI was associated with complex lesion characteristics, such as the lesion length, lesion angle, calcification, and Medina classification. In the multivariate logistic regression analysis, the lesion length (per 10-mm increase: odds ratio (OR), 1.477; 95% confidence interval (CI), 1.161‒1.879; P = 0.002), lesion angle ≥ 45° (versus lesion angle < 45°: OR, 4.244; 95% CI, 1.187‒15.171; P = 0.026), and Medina classification (0,1,1) / (1,1,1) (versus other lesions: OR, 14.843; 95% CI, 6.235‒35.334; P < 0.001) were significantly associated with PMI. Of the 24 lesions with lesion angle ≥ 45° in the PMI group, 14 had final TIMI flow grade ≤ 2 in side branches and 9 had transient slow flow in main branches/transient ST elevation during PCI. Of the 87 lesions with Medina classification (1,1,1) / (0,1,1), 19 had final TIMI grade ≤ 2 in side branches. In conclusion, the lesion length, lesion angle ≥ 45°, and Medina classification (0,1,1) / (1,1,1) were significantly associated with PMI in contemporary elective PCI. Preventing flow limitation in both side branches and main vessels in elective PCI for the diffuse long, angulated, or true bifurcation lesions is important.

Comparison of Computed Tomography Angiography Versus Invasive Angiography to Assess Medina Classification in Coronary Bifurcations.

The Medina classification is used to determine the presence of significant stenosis (≥50%) within each of the 3 arterial segments of coronary bifurcation in invasive coronary angiography (ICA). The utility of coronary computed tomography angiography (coronary CTA) for assessment of Medina classification is unknown. We aimed to compare the agreement and reproducibility of Medina classification between ICA and coronary CTA, and evaluate its ability to predict side branch (SB) occlusion following percutaneous coronary intervention (PCI). In total 363 patients with 400 bifurcations were included, and 28 (7%) SB occlusions among 26 patients were noted. Total agreement between CTA and ICA for assessment of Medina class was poor (kappa = 0.189), and discordance between both modalities was noted in 253 (63.3%) lesions. Larger diameter ratio between main vessel and SB in CTA, and larger bifurcation angle in ICA were independently associated with discordant Medina assessment. Whereas the interobserver agreement on Medina classification in CTA was moderate (kappa = 0.557), only fair agreement (kappa = 0.346) was observed for ICA. Finally, Medina class with any proximal involvement of main vessel and SB (1.X.1) on CTA or ICA was the most predictive of SB occlusion following PCI with no significant differences between both modalities (area under the curve 0.686 vs 0.663, p = 0.693, respectively). In conclusion, Medina classification was significantly affected by the imaging modality, and coronary CTA improved reproducibility of Medina classification compared with ICA. Both CTA and ICA-derived Medina class with any involvement of the proximal main vessel and SB was predictive of SB occlusion following PCI.

Instantaneous wave-free ratio cutoff values for nonculprit stenosis classification in patients with ST-segment elevation myocardial infarction (an iSTEMI substudy).

OBJECTIVES: The instantaneous wave-free ratio cutoff value of <0.90 for hemodynamic significance of coronary stenoses has been validated in stable patients. We examined different cutoff values in the evaluation of nonculprit stenoses in patients with ST-segment elevation myocardial infarction. METHODS: We measured instantaneous wave-free ratio across nonculprit stenoses in the acute setting and at follow-up in 120 patients with ST-segment elevation myocardial infarction and 157 nonculprit stenoses, of which, 113 patients with 147 nonculprit stenoses completed follow-up. METHODS: The prevalence of nonculprit stenosis hemodynamic significance was 52% in the acute setting and 41% at follow-up. With follow-up, instantaneous wave-free ratio as reference, acute instantaneous wave-free ratio >0.90 had a negative predictive value of 89%. Acute instantaneous wave-free ratio <0.90 had a positive predictive value of 68%. Acute instantaneous wave-free ratio >0.93 had a negative predictive value of 100%. Acute instantaneous wave-free ratio <0.86 and <0.83 had positive predictive values of 71 and 77%. Using acute instantaneous wave-free ratio <0.90 as cutoff for hemodynamic significance yielded the highest degree of classification agreement between acute and follow-up instantaneous wave-free ratio. CONCLUSIONS: In patients with ST-segment elevation myocardial infarction, acute instantaneous wave-free ratio with the cutoff values <0.90 for hemodynamic significance appears optimal in the evaluation of nonculprit stenoses and has a high negative predictive value and a moderate positive predictive value.

Coronary artery disease risk reclassification by a new acoustic-based score.

To determine the potential of a non-invasive acoustic device (CADScor®System) to reclassify patients with intermediate pre-test probability (PTP) and clinically suspected stable coronary artery disease (CAD) into a low probability group thereby ruling out significant CAD. Audio recordings and clinical data from three studies were collected in a single database. In all studies, patients with a coronary CT angiography indicating CAD were referred to coronary angiography. Audio recordings of heart sounds were processed to construct a CAD-score. PTP was calculated using the updated Diamond-Forrester score and patients were classified according to the current ESC guidelines for stable CAD: low < 15%, intermediate 15-85% and high > 85% PTP. Intermediate PTP patients were re-classified to low probability if the CAD-score was ≤ 20. Of 2245 patients, 212 (9.4%) had significant CAD confirmed by coronary angiography ( ≥ 50% diameter stenosis). The average CAD-score was higher in patients with significant CAD (38.4 ± 13.9) compared to the remaining patients (25.1 ± 13.8; p < 0.001). The reclassification increased the proportion of low PTP patients from 13.6% to 41.8%, reducing the proportion of intermediate PTP patients from 83.4% to 55.2%. Before reclassification 7 (3.1%) low PTP patients had CAD, whereas post-reclassification this number increased to 28 (4.0%) (p = 0.52). The net reclassification index was 0.209. Utilization of a low-cost acoustic device in patients with intermediate PTP could potentially reduce the number of patients referred for further testing, without a significant increase in the false negative rate, and thus improve the cost-effectiveness for patients with suspected stable CAD.

Invasive coronary angiography findings across the CAD-RADS classification spectrum.

The recently introduced coronary artery disease reporting and data system (CAD-RADS) evaluated by computed tomography and based on stenosis severity, might not adequately reflect the complexity of CAD. We explored the relationship between CAD-RADS and the spatial distribution, burden, and complexity of lesions by invasive coronary angiography (ICA). Stable patients who underwent coronary computed tomography angiography (CCTA) and ICA comprised the study population. Patients were classified according to the CAD-RADS: 0, No plaque; 1, 1-24% stenosis; 2, 25-49%; 3, 50-69%; 4A, 70-99%; 4B, left main stenosis or 3-vessel obstructive disease; and 5, total occlusion. Based on ICA findings, we calculated the SYNTAX score and the CAD extension index. Ninety-one patients were included, with a mean age of 61.4 ± 10.5 years (74% male). We found significant relationships between CAD-RADS and both the SYNTAX score (p < 0.0001) and the CAD extension index (p < 0.0001), although the complexity of coronary anatomy differed among patients with CAD-RADS ≥ 4A. Among patients with CAD-RADS < 4, the mean segment involvement score (SIS) was 8.4 ± 4.0, 52% of them with a SIS > 5. Of the 30 patients with CAD-RADS 5, 9 (30%) affected distal segments or secondary branches, and 9 (30%) had concomitant severe non-extensive disease at ICA. Regarding the spatial distribution of the non-occluded most severe lesions, 27 (44%) comprised distal segments or secondary branches. In the present study including a high-risk population, we identified diverse coronary anatomy complexity scenarios and relevant differences in spatial distribution sharing the same CAD-RADS classification.

Association between blood neutrophil-to-lymphocyte ratio and severity of coronary artery disease: Evidence from 17 observational studies involving 7017 cases.

This study aimed to evaluate the association between blood neutrophil-to-lymphocyte ratio (NLR) and severity of coronary artery disease (CAD), and investigate the diagnostic ability and optimal cut-off value of NLR in predicting severe stenosis in CAD.A systematic search was conducted in public databases to identify all relevant studies. Weighted mean difference (MD) and 95% confidence interval (CI) were pooled for continuous univariate data, and odds ratios (OR) and 95% CI were calculated for dichotomous multivariate data.Seventeen studies were included in this meta-analysis with a total of 7017 CAD cases. For continuous univariate data, the cases with the highest stenosis category had a significantly higher NLR level than those with lowest stenosis category (MD: 1.57, 95% CI: 1.06-2.09; n = 17). After further classification according to the Gensini or SYNTAX score, the cases with severe stenosis demonstrated a higher NLR than those with mild stenosis (MD: 2.33, 95% CI: 1.22-3.43; n = 6) and moderate stenosis (MD: 1.92, 95% CI: 0.80-3.04; n = 6). Compared with mild stenosis, NLR was also higher in those with moderate-to-severe stenosis (MD: 1.34, 95% CI: 0.77-1.92; n = 6) and moderate stenosis (MD: 0.52, 95% CI: 0.36-0.68; n = 6). For dichotomous multivariate data, high NLR levels were recognized as an independent predictor for severe stenosis in CAD (OR: 1.50, 95% CI: 1.32-1.72; n = 11). NLR showed a diagnostic ability in predicting severe stenosis in CAD (area under receiver operating characteristics [ROC] curve [AUC]: 0.66, 95% CI: 0.64-0.68; n = 8), with the cut-off ranging from 1.95 to 3.97. Subgroup analysis and sensitivity analysis showed the results were robust. Begg's test detected no significant publication biases.This study suggested that high blood NLR was associated with the severity of CAD, and it might be useful for predicting severe stenosis in CAD.

Impact of Routine Invasive Physiology at Time of Angiography in Patients With Multivessel Coronary Artery Disease on Reclassification of Revascularization Strategy: Results From the DEFINE REAL Study.

OBJECTIVES: This study sought to prospectively assess the impact of routine invasive physiology at the time of angiography on reclassification of therapeutic management of multivessel disease (MVD) patients, and to assess how implementation of instantaneous wave-free ratio (iFR) alters the process. BACKGROUND: Routine invasive physiology in intermediate coronary lesions at the time of diagnostic angiography, primarily in patients with single-vessel disease and using fractional flow reserve (FFR), reclassifies coronary revascularization management in 26% to 44% of patients. The role of invasive physiology in patients with MVD is unclear. METHODS: In 18 centers, 484 patients undergoing diagnostic angiography disclosing MVD with lesions >40% by visual assessment were included. Investigators were asked to prospectively define their initial management strategy based on angiography and clinical information. Invasive physiology (FFR or iFR driven) was then performed and final strategy defined. Initial and final vessel, patient, procedural, and overall management were described. Reclassification was defined as the difference between initial and final strategy. RESULTS: The majority of patients were clinically stable (82.2%). Two- and 3-vessel disease was present in 73.3% and 26.7% of patients, respectively. Lesions investigated were "intermediate" with median percent stenosis, median FFR, and median iFR at 60% (interquartile range [IQR]: 50% to 70%), 0.84 (IQR: 0.78 to 0.90), and 0.92 (IQR: 0.85 to 0.96), respectively. Vessel management was reclassified by physiology in 30.0% (249 of 828) of vessels. Patient and overall management were reclassified in 26.9% (130 of 484) and 45.7% (211 of 484) of patients, respectively. Reclassification rates were high irrespective of initial management (optimal medical therapy, percutaneous coronary intervention, or coronary artery bypass grafting), and performance and results of pre-procedural noninvasive tests. Reclassification of overall management in particular increased with the number of vessels investigated (1 vessel: 37.3%; 2 vessels: 45.0%; 3 vessels: 66.7%; p = 0.002). Incorporating iFR in the decision process was associated with investigation of more vessels (p = 0.04) and higher reclassification (p = 0.0001). CONCLUSIONS: In patients with MVD and intermediate coronary lesions, invasive physiology at time of angiography reclassifies revascularization strategy in a large proportion of cases (26.9%) and investigation of more vessels is associated with higher reclassification rates.

Fractional flow reserve derived from coronary computed tomography angiography reclassification rate using value distal to lesion compared to lowest value.

INTRODUCTION: A standardised approach to the interpretation of FFRCT data is currently lacking. We evaluated the rate of reclassification of FFRCT positivity using the FFRCT value distal to an anatomical stenoses compared to the lowest FFRCT value. METHOD: Patients who underwent coronary CTA and FFRCT analysis were eligible. FFRCT value of ≤ 0.80 was considered positive. Positive FFRCT distal to stenosis was defined as those with a stenoses of ≥ 25% with an associated FFRCT value of ≤ 0.80 within 2cm distal to the lesion. Outcome data on subsequent invasive coronary angiography (ICA) and coronary revascularisation were collected with a minimum follow-up of 60 days to account for delay between referral for invasive testing and/or revascularisation and receiving the procedure. RESULT: 192 patients (mean age 60.7 ± 10.6 years, 67.5% men) were included. FFRCT was positive for lowest FFRCT value in 55.7% of patients. Positive FFRCT value distal to stenosis was found in 31.3%. The overall reclassification rate of those positive for lowest FFRCT value to negative for FFRCT value distal to stenosis was 43.9% (p < 0.01). The reclassification rates were most pronounced for those with intermediate stenoses - 67% for those with < 50% stenoses, p < 0.01; 49% for 50-69% stenoses, p < 0.01. Amongst those who underwent ICA, the rate of revascularization was significant higher for those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value (revascularization/ICA = 0.53 vs 0.44, p < 0.01). CONCLUSION: Using FFRCT values distal to a anatomical stenoses, 44% of patients positive for lowest FFRCT value were reclassified as negative for FFRCT value distal to stenosis. Those who underwent ICA, the rate of revascularisation was higher amongst those with positive FFRCT distal to stenosis compared to those positive for lowest FFRCT value.

CAD-RADS(TM) Coronary Artery Disease - Reporting and Data System. An expert consensus document of the Society of Cardiovascular Computed Tomography (SCCT), the American College of Radiology (ACR) and the North American Society for Cardiovascular Imaging (NASCI). Endorsed by the American College of Cardiology.

The intent of CAD-RADS - Coronary Artery Disease Reporting and Data System is to create a standardized method to communicate findings of coronary CT angiography (coronary CTA) in order to facilitate decision-making regarding further patient management. The suggested CAD-RADS classification is applied on a per-patient basis and represents the highest-grade coronary artery lesion documented by coronary CTA. It ranges from CAD-RADS 0 (Zero) for the complete absence of stenosis and plaque to CAD-RADS 5 for the presence of at least one totally occluded coronary artery and should always be interpreted in conjunction with the impression found in the report. Specific recommendations are provided for further management of patients with stable or acute chest pain based on the CAD-RADS classification. The main goal of CAD-RADS is to standardize reporting of coronary CTA results and to facilitate communication of test results to referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will provide a framework of standardization that may benefit education, research, peer-review and quality assurance with the potential to ultimately result in improved quality of care.

Quantification of the Effect of Pressure Wire Drift on the Diagnostic Performance of Fractional Flow Reserve, Instantaneous Wave-Free Ratio, and Whole-Cycle Pd/Pa.

BACKGROUND: Small drifts in intracoronary pressure measurements (±2 mm Hg) can affect stenosis categorization using pressure indices. This has not previously been assessed for fractional flow reserve (FFR), instantaneous wave-free ratio (iFR), and whole-cycle distal pressure/proximal pressure (Pd/Pa) indices. METHODS AND RESULTS: Four hundred forty-seven stenoses were assessed with FFR, iFR, and whole-cycle Pd/Pa. Cut point values for significance were predefined as ≤0.8, <0.90, and <0.93, respectively. Pressure wire drift was simulated by offsetting the distal coronary pressure trace by ±2 mm Hg. FFR, iFR, and whole-cycle Pd/Pa indices were recalculated and stenosis misclassification quantified. Median (±median absolute deviation) values for FFR, iFR, and whole-cycle Pd/Pa were 0.81 (±0.11), 0.90 (±0.07), and 0.93 (±0.06), respectively. For the cut point of FFR, iFR, and whole-cycle Pd/Pa, 34.6% (155), 50.1% (224), and 62.2% (278) of values, respectively, lay within ±0.05 U. With ±2 mm Hg pressure wire drift, 21% (94), 25% (110), and 33% (148) of the study population were misclassified with FFR, iFR, and whole-cycle Pd/Pa, respectively. Both FFR and iFR had significantly lower misclassification than whole-cycle Pd/Pa (P<0.001). There was no statistically significant difference between the diagnostic performance of FFR and iFR (P=0.125). CONCLUSIONS: In a substantial proportion of cases, small amounts of pressure wire drift are enough to cause stenoses to change classification. Whole-cycle Pd/Pa is more vulnerable to such reclassification than FFR and iFR.

Trends in Coronary Atherosclerosis: A Tale of Two Population Subgroups.

BACKGROUND: We previously investigated trends in subclinical coronary artery disease and associated risk factors among autopsied non-elderly adults who died from nonnatural causes. Although grade of atherosclerosis declined from 1981 through 2009, the trend was nonlinear, ending in 1995, concurrent with increasing obesity/diabetes in this population. The previous study used linear regression and examined trends for all 4 major epicardial coronary arteries combined. The present investigation of coronary artery disease trends for the period 1995 through 2012 was prompted by a desire for more detailed examination of more recent coronary artery disease trends in light of reports that the epidemics of obesity and diabetes have slowed and are perhaps ending. METHODS: This population-based series of cross-sectional investigations identified all Olmsted County, Minnesota residents aged 16-64 years who died 1995 through 2012 (N = 2931). For decedents with nonnatural manner of death, pathology reports were reviewed for grade of atherosclerosis assigned each major epicardial coronary artery. Using logistic regression, we estimated calendar-year trends in grade (unadjusted and age- and sex-adjusted) for each artery, initially as an ordinal measure (range, 0-4); then, based on evidence of nonproportional odds, as a dichotomous variable (any atherosclerosis, yes/no) and as an ordinal measure for persons with atherosclerosis (range, 1-4). RESULTS: Of 474 nonnatural deaths, 453 (96%) were autopsied; 426 (90%) had coronary stenosis graded. In the ordinal-logistic model for trends in coronary artery disease grade (range, 0-4), the proportional odds assumption did not hold. In subsequent analysis as a dichotomous outcome (grades 0 vs 1-4), each artery exhibited a significant temporal decline in the proportion with any atherosclerosis. Conversely, for subjects with coronary artery disease grade 1-4, age- and sex-adjusted ordinal regression revealed no change over time in 2 arteries and statistically significant temporal increases in severity in 2 arteries. CONCLUSIONS: Findings suggest that efforts to prevent coronary artery disease onset have been relatively successful. However, statistically significant increases in the grade of atherosclerosis in 2 arteries among persons with coronary artery disease may be indicative of a major public health challenge.

Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II).

OBJECTIVES: The purpose of this study was to assess the diagnostic accuracy of the instantaneous wave-free ratio (iFR) to characterize, outside of a pre-specified range of values, stenosis severity, as defined by fractional flow reserve (FFR) ≤0.80, in a prospective, independent, controlled, core laboratory-based environment. BACKGROUND: Studies with methodological heterogeneity have reported some discrepancies in the classification agreement between iFR and FFR. The ADVISE II (ADenosine Vasodilator Independent Stenosis Evaluation II) study was designed to overcome limitations of previous iFR versus FFR comparisons. METHODS: A total of 919 intermediate coronary stenoses were investigated during baseline and hyperemia. From these, 690 pressure recordings (n = 598 patients) met core laboratory physiology criteria and are included in this report. RESULTS: The pre-specified iFR cut-off of 0.89 was optimal for the study and correctly classified 82.5% of the stenoses, with a sensitivity of 73.0% and specificity of 87.8% (C statistic: 0.90 [95% confidence interval (CI): 0.88 to 0.92, p < 0.001]). The proportion of stenoses properly classified by iFR outside of the pre-specified treatment (≤0.85) and deferral (≥0.94) values was 91.6% (95% CI: 88.8% to 93.9%). When combined with FFR use within these cut-offs, the percent of stenoses properly classified by such a pre-specified hybrid iFR-FFR approach was 94.2% (95% CI: 92.2% to 95.8%). The hybrid iFR-FFR approach obviated vasodilators from 65.1% (95% CI: 61.1% to 68.9%) of patients and 69.1% (95% CI: 65.5% to 72.6%) of stenoses. CONCLUSIONS: The ADVISE II study supports, on the basis rigorous methodology, the diagnostic value of iFR in establishing the functional significance of coronary stenoses, and highlights its complementariness with FFR when used in a hybrid iFR-FFR approach. (ADenosine Vasodilator Independent Stenosis Evaluation II-ADVISE II; NCT01740895).

Definitions and classifications of bifurcation lesions and treatment.

This article introduces the new terminology proposed by the European Bifurcation Club in order to simplify the identification, description, localisation and measurement of coronary bifurcation lesions as well as the selection of appropriate treatment strategies. A bifurcation lesion is a coronary artery narrowing occurring adjacent to, and/or involving, the origin of a significant side branch that you do not want to lose. The very simple Medina classification is intended for exchange and clinical research purposes. It is combined with a clear side branch definition and is associated with multiple measurement and imaging modalities, which take into account the complexity of lesions and treatments. Dedicated angiography as well as 3D angiography and multislice computed tomography are absolutely necessary for measurement of the bifurcation angles. The MADS (Main, Across, Distal, Side) classification is based on the final position of the stents in the bifurcation and on the order in which stents are implanted according to a strategy reflecting lesion and technique complexity. Although this classification still seems exhaustive, it does not involve the numerous guide and balloon manoeuvres, which would require a thorough a posteriori electronic classification of all inherent specific technical details.

Disturbed coronary hemodynamics in vessels with intermediate stenoses evaluated with fractional flow reserve: a combined analysis of epicardial and microcirculatory involvement in ischemic heart disease.

BACKGROUND: In chronic ischemic heart disease, focal stenosis, diffuse atherosclerotic narrowings, and microcirculatory dysfunction (MCD) contribute to limit myocardial flow. The prevalence of these ischemic heart disease levels in fractional flow reserve (FFR) interrogated vessels remains largely unknown. METHODS AND RESULTS: Using intracoronary measurements, 91 coronaries (78 patients) with intermediate stenoses were classified in 4 FFR and coronary flow reserve (CFR) agreement groups, using FFR>0.80 and CFR<2 as cutoffs. Index of microcirculatory resistance (IMR) and atherosclerotic burden (Gensini score) were also assessed. MCD was assumed when IMR≥29.1 (75(th) percentile). Fifty-four (59.3%) vessels had normal FFR, from which only 20 (37%) presented both normal CFR and IMR. Among vessels with FFR>0.80, most (63%) presented disturbed hemodynamics: abnormal CFR in 28 (52%) and MCD in 18 (33%). Vessels with FFR>0.80 presented higher IMR [adjusted mean 27.6 (95% confidence interval, 23.4-31.8)] than those with FFR≤0.80 [17.3 (95% confidence interval, 13.0-21.7), p=0.001]. Atherosclerotic burden was inversely correlated with CFR (r=-0.207, P=0.055), and in vessels with FFR>0.80 and CFR<2 (n=28, 39%), IMR had a wide dispersion (7-72.7 U), suggesting a combination of diffuse atherosclerotic narrowings and MCD. Vessels with FFR≤0.80 and normal CFR presented the lowest IMR, suggesting a preserved microcirculation. CONCLUSIONS: A substantial number of coronary arteries with stenoses showing an FFR>0.80 present disturbed hemodynamics. Integration of FFR, CFR, and IMR supports the existence of differentiated patterns of ischemic heart disease that combine focal and diffuse coronary narrowings with variable degrees of MCD.

Additional value of adenosine-stress dynamic CT myocardial perfusion imaging in the reclassification of severity of coronary artery stenosis at coronary CT angiography.

AIM: To assess the additional value of adenosine-stress dynamic computed tomography (CT) perfusion (ASDCTP) imaging compared with coronary CT angiography (CCTA) alone to detect significant coronary artery stenosis for each threshold of 50% and 70% diameter stenosis. MATERIALS AND METHODS: The study included 34 patients (65 ± 11 years, 79% men) with suspected coronary artery diseases who underwent ASDCTP imaging using a 128-section dual-source CT (DSCT) and invasive coronary angiography (ICA). Two investigators classified coronary artery stenosis on CCTA as severe or not. If appropriate image quality could not be acquired due to artefacts, the segment was classified as a lesion with significant stenosis. After the interpretation of ASDCTP imaging, the degree of stenosis was reclassified. All parameters of diagnostic accuracy were calculated before and after ASDCTP analysis for detection of significant coronary artery stenosis with ICA as the reference standard. RESULTS: The diagnostic accuracy parameters per vessel for the detection of ≥50% stenosis before and after ASDCTP analysis changed as follows: sensitivity, from 80% to 83%; specificity, from 83% to 98%; positive predictive value (PPV), from 87% to 98%; and negative predictive value (NPV), from 75% to 80%. The addition of ASDCTP resulted in reclassification from one class of stenosis severity to another in a significant number of vessels with threshold of 50% stenosis [net reclassification improvement (NRI), 0.176; p < 0.01]. Conversely, the addition of ASDCTP did not result in significant reclassification of stenosis severity in vessels with threshold of 70% stenosis (NRI, 0.034; p = 0.51). CONCLUSIONS: ASDCTP imaging provides incremental value in the detection of significant coronary artery stenosis using a threshold of 50%.

Classification performance of instantaneous wave-free ratio (iFR) and fractional flow reserve in a clinical population of intermediate coronary stenoses: results of the ADVISE registry.

AIMS: To evaluate the classification agreement between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR) in patients with angiographic intermediate coronary stenoses. METHODS AND RESULTS: Three hundred and twelve patients (339 stenoses) with angiographically intermediate stenoses were included in this international clinical registry. The iFR was calculated using fully automated algorithms. The receiver operating characteristic (ROC) curve was used to identify the iFR optimal cut-point corresponding to FFR 0.8. The classification agreement of coronary stenoses as significant or non-significant was established between iFR and FFR and between repeated FFR measurements for each 0.05 quantile of FFR values, from 0.2 to 1. Close agreement was observed between iFR and FFR (area under ROC curve= 86%). The optimal iFR cut-off (for an FFR of 0.80) was 0.89. After adjustment for the intrinsic variability of FFR, the classification agreement (accuracy) between iFR and FFR was 94%. Amongst the stenoses classified as non-significant by iFR (>0.89) and as significant by FFR (≤0.8), 81% had associated FFR values located within the FFR "grey-zone" (0.75-0.8) and 41% within the 0.79-0.80 FFR range. CONCLUSIONS: In a population of intermediate coronary stenoses, the classification agreement between iFR and FFR is excellent and similar to that of repeated FFR measurements in the same sample. Vasodilator-independent assessment of intermediate stenosis seems applicable and may foster adoption of coronary physiology in the catheterisation laboratory.

Angiographic lesion severity and subsequent myocardial infarction.

We sought to determine the angiographic severity of coronary lesions leading to ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) with a focus on determining the impact of interval from initial angiogram to subsequent clinical event. In the late 1980s angiographic data on lesion characteristics that culminated in STEMI and NSTEMI were obtained from angiograms obtained several months before MI. It is not clear whether the conclusions on lesion severity would be different if elapsed interval from baseline angiogram to clinical event was factored in the analysis. From 2003 through 2010, we identified 84 patients with NSTEMI and 41 patients with STEMI in vessels without previous intervention. These patients had ≥1 previous angiographic study at our center. Angiograms were reanalyzed with quantitative coronary angiography, and relevant clinical data were obtained from medical records. Similar to previous studies, 71% of patients with STEMI and 63% of patients with NSTEMI had <50% baseline stenosis at the culprit site when the interval from initial angiogram to MI was >3 months. Interestingly, lesions that led to STEMI ≤3 months after evaluation were more severe than those leading to STEMI in >3 months (59 ± 31% vs 36 ± 21%, p = 0.02) with 57% of lesions having >50% stenosis. Although most MIs occurred at sites that did not have significant obstruction when examined >3 months before MI, most baseline lesions showed significant luminal narrowing when examined ≤3 months before STEMI. In conclusion, high-grade coronary stenosis may be an important predictor of STEMI in subsequent months.

Definitions and methodology for the grayscale and radiofrequency intravascular ultrasound and coronary angiographic analyses.

OBJECTIVES: In a prospective study of the natural history of coronary atherosclerosis using angiography and grayscale and radiofrequency intravascular ultrasound (IVUS)-virtual histology (VH), larger plaque burden, smaller luminal area, and plaque composition thin-cap fibroatheroma emerged as independent predictors of future adverse cardiovascular events. BACKGROUND: The methodology for IVUS-VH classification for an in vivo natural history study and the prospective image mapping by angiography and grayscale and IVUS-VH have not been established. METHODS: All culprit and nonculprit lesions (defined as ≥ 30% angiographic visual diameter stenoses) were analyzed. Three epicardial vessels as well as all ≥ 1.5-mm-diameter side branches were divided into 29 CASS (Coronary Artery Surgery Study) segments. Each CASS segment was then subdivided into 1.5-mm-long subsegments, and dimensions were analyzed. All grayscale and IVUS-VH slices from the proximal 6 to 8 cm of the 3 coronary arteries were analyzed, with lesions defined as having more than 3 consecutive slices with ≥ 40% plaque burden categorized as: 1) VH thin-cap fibroatheroma; 2) thick-cap fibroatheroma; 3) pathological intimal thickening; 4) fibrotic plaque; or 5) fibrocalcific plaque. The locations of angiographic and grayscale and IVUS-VH lesions were recorded in relation to the corresponding coronary artery ostium and nearby side branches. RESULTS: The 3-year cumulative rate of major adverse cardiovascular events was 20.4%. Events were adjudicated to culprit lesions in 12.9% of patients and to nonculprit lesions in 11.6%. On multivariate analysis, nonculprit lesions associated with recurrent events were characterized by a plaque burden ≥ 70% (hazard ratio: 5.03; 95% confidence interval: 2.51 to 10.11; p < 0.0001), a minimal luminal area ≤ 4.0 mm(2) (hazard ratio: 3.21; 95% confidence interval: 1.61 to 6.42; p = 0.001), and IVUS-VH phenotype of a thin-cap fibroatheroma (hazard ratio: 3.35; 95% confidence interval: 1.77 to 6.36; p < 0.001). CONCLUSIONS: Three-vessel multimodality coronary artery imaging was feasible and allowed the identification of lesion-level predictors for future events in this natural history study.