Safety of Revascularization Deferral of Left Main Stenosis Based on Instantaneous Wave-Free Ratio Evaluation

ObjectivesThe aim of this study was to assess the long-term clinical outcomes of patients with left main coronary artery (LM) stenosis in whom treatment strategy was based on the instantaneous wave-free ratio (iFR).BackgroundThe overall safety of iFR to guide revascularization decision making in patients with stable coronary artery disease has been established. However, no study has examined the safety of deferral of revascularization of LM disease on the basis of iFR.MethodsThis multicenter observational study included 314 patients in whom LM stenosis was deferred (n = 163 [51.9%]) or revascularized (n = 151 [48.1%]) according to the iFR cutoff ≤0.89. The primary endpoint was a composite of all-cause death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization. The secondary endpoints were each individual component of the primary endpoint and also cardiac death.ResultsAt a median follow-up period of 30 months, the primary endpoint occurred in 15 patients (9.2%) in the deferred group and 22 patients (14.6%) in the revascularized group (hazard ratio: 1.45; 95% confidence interval: 0.75 to 2.81; p = 0.26), indicating no evidence of a significant difference between the 2 groups. For the secondary endpoints, findings in the iFR-based deferral and revascularization groups were as follows: all-cause death, 3.7% versus 4.6%; cardiac death, 1.2% versus 2.0%; nonfatal myocardial infarction, 2.5% versus 5.3%; and target lesion revascularization, 4.3% versus 5.3% (p > 0.05 for all).ConclusionsDeferral of revascularization of LM stenosis on the basis of iFR appears to be safe, with similar long-term outcomes to those in patients in whom LM revascularization was performed according to iFR values.     

El cociente de flujo cuantitativo en pacientes con estenosis aórtica grave y lesiones coronarias intermedias

Introduction and objectivesQuantitative flow ratio (QFR) is a novel noninvasive method for evaluating coronary physiology. However, data on the QFR in patients with aortic stenosis (AS) and coronary artery disease are scarce. Thus, we compared the diagnostic performance of the QFR with that of the resting distal to aortic coronary pressure (Pd/Pa) ratio, fractional flow reserve (FFR), and instantaneous wave-free ratio (iFR), as well as angiographic indices.MethodsA total of 221 AS patients with 416 vessels undergoing FFR/iFR measurements were enrolled in the study.ResultsThe mean percent diameter stenosis (%DS) was 58.6% ± 13.4% and the mean Pd/Pa ratio, FFR, iFR, and QFR were 0.95 ± 0.03, 0.85 ± 0.07, 0.90 ± 0.04, and 0.84 ± 0.07, respectively. A FFR ≤ 0.80 was noted in 26.0% of interrogated vessels, as well as an iFR ≤ 0.89 in 33.2% and QFR ≤ 0.80 in 31.7%. The QFR had better agreement with FFR (intraclass correlation coefficient [ICC], 0.96; 95% confidence interval [95%CI], 0.95-0.96) than with the iFR (ICC, 0.79; 95%CI, 0.75-0.82) and Pd/Pa ratio (ICC, 0.52; 95%CI, 0.44-0.58). In addition, the QFR showed better diagnostic accuracy (98.6% vs 94.2%; P < .001) and discriminant function (area under the curve = 0.996 vs 0.988; P < .001) when the iFR was used as the reference instead of FFR.ConclusionsIn patients with AS, the QFR has good agreement with both FFR and iFR. However, the agreement appears to be even better when the iFR is used as the reference, presumably due to the complex nature of the coronary physiology in the assessment of coronary artery disease in patients with severe AS.     

Prognostic Implications of Post-Intervention Resting Pd/Pa and Fractional Flow Reserve in Patients With Stent Implantation

ObjectivesThis study sought to investigate the prognostic implications of post–percutaneous coronary intervention (PCI) nonhyperemic pressure ratios compared with that of post-PCI fractional flow reserve (FFR).BackgroundFFR measured after PCI has been shown to possess prognostic implications. However, the prognostic value of post-PCI nonhyperemic pressure ratios has not yet been clarified.MethodsA total of 588 patients who underwent PCI with available both post-PCI FFR and resting distal coronary pressure-to-aortic pressure ratio (Pd/Pa) were analyzed. Post-PCI FFR and Pd/Pa were measured after successful angiographic stent implantation. The primary outcome was target vessel failure (TVF) up to 2 years, defined as a composite of cardiac death, target vessel–related myocardial infarction, and clinically driven target vessel revascularization. Prognosis of patients according to post-PCI Pd/Pa was compared with that of post-PCI FFR.ResultsDespite angiographically successful PCI, 18.5% had post-PCI FFR ≤0.80 and 36.9% showed post-PCI Pd/Pa ≤0.92. In post-PCI Pd/Pa >0.92 group, 93.8% of patients showed post-PCI FFR >0.80. Conversely, 60.4% of patients showed post-PCI FFR >0.80 in post-PCI Pd/Pa ≤0.92 group. Although there was significant difference in TVF according to post-PCI FFR (≤0.80 vs. >0.80: 10.3% vs. 2.5%; p < 0.001) and Pd/Pa (≤0.92 vs. >0.92: 6.2% vs. 2.5%; p = 0.029), the reclassification ability of model for TVF was increased only with post-PCI FFR (net reclassification index 0.627; p = 0.003; integrated discrimination index 0.019; p = 0.015), but not with post-PCI Pd/Pa, compared with model including clinical factors. Compared with patients with post-PCI Pd/Pa >0.92, patients with post-PCI Pd/Pa ≤0.92 and FFR ≤0.80 had significantly higher risk of TVF (10.4% vs. 2.5%; adjusted hazard ratio: 4.204; 95% confidence interval: 1.521 to 11.618; p = 0.006); however, those with post-PCI Pd/Pa ≤0.92 but FFR >0.80 showed similar risk of TVF (3.5% vs. 2.5%; adjusted hazard ratio: 1.327; 95% confidence interval: 0.398 to 4.428; p = 0.645).ConclusionsOver one-half of the patients with abnormal post-PCI Pd/Pa ≤0.92 showed post-PCI FFR >0.80. Compared with post-PCI FFR, post-PCI Pd/Pa showed limited reclassification ability for the occurrence of TVF. Among patients with abnormal post-PCI Pd/Pa, only patients with positive post-PCI FFR showed significantly higher risk of TVF than did those with post-PCI Pd/Pa >0.92. (Prognostic Perspective of Invasive Hyperemic and Non-Hyperemic Physiologic Indices Measured After Percutaneous Coronary Intervention [PERSPECTIVEPCI]; NCT04265443)     

Prognostic Implications of Plaque Characteristics and Stenosis Severity in Patients With Coronary Artery Disease

BackgroundAlthough the presence of ischemia is a key prognostic factor in patients with coronary artery disease, the presence of high-risk plaque characteristics (HRPC) is also associated with increased risk of cardiovascular events. Limited data exist regarding the prognostic implications of combined information on physiological stenosis severity assessed by fractional flow reserve (FFR) and plaque vulnerability by coronary computed tomography angiography (CTA)–defined HRPC.ObjectivesThe current study aimed to evaluate the: 1) association between physiological stenosis severity and coronary CTA-defined HRPC; and 2) prognostic implications of coronary CTA-defined HRPC according to physiological stenosis severity in patients with coronary artery disease.MethodsA total of 772 vessels (299 patients) evaluated by both coronary CTA and FFR were analyzed. The presence and number of HRPC (minimum lumen area <4 mm², plaque burden ≥70%, low attenuating plaque, positive remodeling, napkin-ring sign, or spotty calcification) were assessed using coronary CTA images. The risk of vessel-oriented composite outcome (VOCO) (a composite of vessel-related ischemia-driven revascularization, vessel-related myocardial infarction, or cardiac death) at 5 years was compared according to the number of HRPC and FFR categories.ResultsThe proportion of lesions with ≥3 HRPC was significantly decreased according to the increase in FFR values (58.6%, 46.5%, 36.8%, 15.7%, and 3.5% for FFR ≤0.60, 0.61 to ≤0.70, 0.71 to ≤0.80, 0.81 to ≤0.90, and >0.90, respectively; overall p value <0.001). Both FFR and number of HRPC showed significant association with the estimated risk of VOCO (p = 0.008 and p = 0.023, respectively). In the FFR >0.80 group, lesions with ≥3 HRPC showed significantly higher risk of VOCO than those with <3 HRPC (15.0% vs. 4.3%; hazard ratio: 3.964; 95% confidence interval: 1.451 to 10.828; p = 0.007). However, there was no significant difference in the risk of VOCO according to HRPC in the FFR ≤0.80 group. By multivariable analysis, the presence of ≥3 HRPC was independently associated with the risk of VOCO in the FFR >0.80 group.ConclusionsPhysiological stenosis severity and the number of HRPC were closely related, and both components had significant association with the risk of clinical events. However, the prognostic implication of HRPC was different according to FFR. Integration of both physiological stenosis severity and plaque vulnerability would provide better prognostic stratification of patients than either individual component alone, especially in patients with FFR >0.80. (Clinical Implication of 3-vessel Fractional Flow Reserve [3V FFR-FRIENDS study]; NCT01621438)     

Coronary Circulatory Indexes in Non-Infarct-Related Vascular Territories in a Porcine Acute Myocardial Infarction Model

ObjectivesThe aim of this study was to evaluate temporal changes in coronary hemodynamic and physiological indexes in the non-infarct-related artery (IRA), which might be affected by adjacent infarcted myocardium, using an experimental animal model of acute myocardial infarction.BackgroundThere has been debate on the reliability of fractional flow reserve and resting pressure-derived indexes, including instantaneous wave-free ratio, in the non-IRA in patients with acute ST-segment elevation myocardial infarction.MethodsIn Yorkshire swine, acute myocardial infarction was simulated with selective balloon occlusion at the left circumflex coronary artery as the IRA for 30 min. Non-IRA stenosis was created using bare-metal stent implantation in the left anterior descending coronary artery 4 weeks before the experiments. Serial changes in systemic hemodynamic status, coronary pressure, and Doppler-derived coronary flow velocity were measured in a nonoccluded left anterior descending coronary artery as the non-IRA from baseline, balloon occlusion of the left circumflex coronary artery, and 15 min after reperfusion of the left circumflex coronary artery.ResultsAmong the 6 experimental subjects, the median diameter stenosis of the non-IRA was 33.9% (interquartile range: 21.7% to 46.1%). During balloon occlusion of the IRA, there were transient significant changes in both resting and hyperemic aortic pressure, distal coronary pressure, averaged peak velocity, transstenotic pressure gradient, and microvascular resistance of the non-IRA (p < 0.020 for all). After reperfusion of the IRA, the resting averaged peak velocity (p = 0.002) and resting transstenotic pressure gradient (p = 0.004) were significantly increased and resting microvascular resistance (p = 0.004) was significantly decreased compared with their values in the baseline phase. However, the hyperemic averaged peak velocity (p = 0.479), hyperemic transstenotic pressure gradient (p = 0.778), and hyperemic microvascular resistance (p = 0.816) were not significantly different compared with those in the baseline phase. After reperfusion, fractional flow reserve in the non-IRA was not significantly different (0.94 ± 0.01 vs. 0.93 ± 0.01; p = 0.353), while coronary flow reserve (1.93 ± 0.07 vs. 1.36 ± 0.07; p = 0.025) and instantaneous wave-free ratio (0.97 ± 0.01 vs. 0.93 ± 0.01; p = 0.001) were significantly lower than baseline values.ConclusionsIn a porcine model of acute myocardial infarction, occlusion of the IRA induced significant changes in systemic hemodynamic status and coronary circulatory indexes of the non-IRA. However, after reperfusion of the IRA, fractional flow reserve did not change significantly, whereas coronary flow reserve and instantaneous wave-free ratio showed significant changes compared with baseline values.     

Contribution of Age-Related Microvascular Dysfunction to Abnormal Coronary: Hemodynamics in Patients With Ischemic Heart Disease

ObjectivesThis study sought to investigate the contribution of age-related microcirculatory dysfunction to abnormal coronary hemodynamics in patients with coronary atherosclerosis.BackgroundImpairment in myocardial blood supply in patients with coronary atherosclerosis can be accentuated due to age-related changes in microcirculatory function.MethodsIntracoronary pressure and flow were measured with the Doppler technique in 299 vessels (228 patients), and the thermodilution technique in 120 vessels (99 patients). In 172 patients, Doppler measurements were also performed in unobstructed vessels. Associations of coronary hemodynamics with aging were studied in both the stenosed and unobstructed arteries.ResultsAging was associated with a progressive increase in minimal microvascular resistance and a progressive decrease in hyperemic flow in both obstructed and nonobstructed coronary arteries. As such, coronary flow reserve decreased with advancing age. Epicardial stenosis severity assessed by resting Pd/Pa, basal stenosis resistance index, and hyperemic stenosis resistance index was equivalent across age groups. By contrast, fractional flow reserve increased with advancing age. Consequently, the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of concomitant focal epicardial and diffuse or microvascular disease (relative risk: 1.6; 95% confidence interval: 1.1 to 2.3; p = 0.017) increased with advancing age, whilst the adjusted risk of a fractional flow reserve/coronary flow reserve pattern reflective of non–flow-limiting stenosis with a healthy microcirculation decreased (relative risk: 0.7; 95% CI: 0.5 to 1.0; p = 0.022).ConclusionsAging is associated with progressive pan-myocardial impairment of coronary vasodilatory capacity due to an increase in minimal microvascular resistance. Concomitant aging-related impairment in microvascular function impacts the pathophysiology of ischemic heart disease in the individual patient and is not adequately identified by hyperemic coronary pressure measurements alone.     

Stress Myocardial Blood Flow Ratio by Dynamic CT Perfusion Identifies Hemodynamically Significant CAD

ObjectivesThe aim of this study was to evaluate the diagnostic accuracy of stress myocardial blood flow ratio (SFR), a novel parameter derived from stress dynamic computed tomographic perfusion (CTP), for the detection of hemodynamically significant coronary stenosis.BackgroundA comprehensive cardiac computed tomographic protocol combining coronary computed tomographic angiography (CTA) and CTP can provide a simultaneous assessment of both coronary artery anatomy and ischemia.MethodsPatients with chest pain scheduled for invasive angiography were prospectively enrolled in this study. Stress dynamic CTP was performed followed by coronary CTA using a second-generation dual-source computed tomographic system. At subsequent invasive angiography, fractional flow reserve was performed to identify hemodynamically significant stenosis. For each coronary territory, SFR was defined as the ratio of hyperemic myocardial blood flow (MBF) in an artery with stenosis to hyperemic MBF in a nondiseased artery. The diagnostic accuracy of SFR to identify hemodynamically significant stenosis was determined against the reference standard of invasive fractional flow reserve ≤0.80.ResultsA total of 82 patients (mean age 58.5 ± 10 years) with 101 vessels with either 1- or 2-vessel disease were included. By FFR, 48 (47.5%) vessels were deemed hemodynamically significant. Hyperemic MBF and SFR were lower for vessels with hemodynamically significant lesions (95.1 ± 32.4 ml/100 ml/min vs. 142.5 ± 31.2 ml/100 ml/min and 0.66 ± 0.14 vs. 0.90 ± 0.07, respectively; p < 0.01 for both). When compared with ≥50% stenosis by CTA, the specificity for detecting ischemia by SFR increased from 43% to 91%, while the sensitivity decreased from 95% to 62%. Accordingly, the positive and negative predictive values were 85% and 73%, respectively. The combination of stenosis ≥50% by CTA and SFR resulted in an area under the curve of 0.91, which was significantly higher compared with hyperemic MBF (area under the curve = 0.79; p = 0.013).ConclusionsCalculation of SFR by dynamic CTP provides a novel and accurate method to identify flow-limiting coronary stenosis.     

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement

ObjectivesThis study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis.BackgroundThe prognostic value of stress dynamic CTP with CTDE is unknown.MethodsParticipants were 540 patients with suspected or known CAD. Major adverse cardiac event(s) (MACE) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score ≥4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE.ResultsDuring a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD (≥50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p = 0.028) and from 0.61 to 0.73 in patients with known CAD (p = 0.004). IPD and scar score of ≥4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p = 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p = 0.001] and 3.2 [p = 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or ≥70% stenosis (12.4% vs. 3.6%; p < 0.001).ConclusionsStress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification.     

Comparison Between the Performance of Quantitative Flow Ratio and Perfusion Imaging for Diagnosing Myocardial Ischemia

ObjectivesThis study compared the performance of the quantitative flow ratio (QFR) with single-photon emission computed tomography (SPECT) and positron emission tomography (PET) myocardial perfusion imaging (MPI) for the diagnosis of fractional flow reserve (FFR)−defined coronary artery disease (CAD).BackgroundQFR estimates FFR solely based on cine contrast images acquired during invasive coronary angiography (ICA). Head-to-head studies comparing QFR with noninvasive MPI are lacking.MethodsA total of 208 (624 vessels) patients underwent technetium-⁹⁹m tetrofosmin SPECT and [¹⁵O]H₂O PET imaging before ICA in conjunction with FFR measurements. ICA was obtained without using a dedicated QFR acquisition protocol, and QFR computation was attempted in all vessels interrogated by FFR (552 vessels).ResultsQFR computation succeeded in 286 (52%) vessels. QFR correlated well with invasive FFR overall (R = 0.79; p < 0.001) and in the subset of vessels with an intermediate (30% to 90%) diameter stenosis (R = 0.76; p < 0.001). Overall, per-vessel analysis demonstrated QFR to exhibit a superior sensitivity (70%) in comparison with SPECT (29%; p < 0.001), whereas it was similar to PET (75%; p = 1.000). Specificity of QFR (93%) was higher than PET (79%; p < 0.001) and not different from SPECT (96%; p = 1.000). As such, the accuracy of QFR (88%) was superior to both SPECT (82%; p = 0.010) and PET (78%; p = 0.004). Lastly, the area under the receiver operating characteristics curve of QFR, in the overall sample (0.94) and among vessels with an intermediate lesion (0.90) was higher than SPECT (0.63 and 0.61; p < 0.001 for both) and PET (0.82; p < 0.001 and 0.77; p = 0.002), respectively.ConclusionsIn this head-to-head comparative study, QFR exhibited a higher diagnostic value for detecting FFR-defined significant CAD compared with perfusion imaging by SPECT or PET.     

Fractional Flow Reserve and Instantaneous Wave-Free Ratio for Nonculprit Stenosis in Patients With Acute Myocardial Infarction

Objectives

The aim of this study was to compare the changes of fractional flow reserve (FFR) or instantaneous wave-free ratio (iFR) with severity of epicardial coronary stenosis between nonculprit vessel of acute myocardial infarction (AMI) and stable ischemic heart disease (SIHD).

CT FFR for Ischemia-Specific CAD With a New Computational Fluid Dynamics Algorithm: A Chinese Multicenter Study

ObjectivesThe aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics–based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia.BackgroundA new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated.MethodsA total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics–based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and “gray zone” lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed.ResultsPer vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p < 0.001 for all). No significant difference in diagnostic accuracy was observed in the “gray zone” range versus the other 2 lesion groups (FFR ≤0.75 and >0.80; p = 0.397) and in patients with “gray zone” versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and <400 (p = 0.393).ConclusionsThis novel computational fluid dynamics–based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.     

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

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

Risk Stratification With the Use of Coronary Computed Tomographic Angiography in Patients With Nonobstructive Coronary Artery Disease

ObjectivesThe purpose of this study was to develop a risk prediction model for patients with nonobstructive CAD.BackgroundAmong stable chest pain patients, most cardiovascular (CV) events occur in those with nonobstructive coronary artery disease (CAD). Thus, developing tailored risk prediction approaches in this group of patients, including CV risk factors and CAD characteristics, is needed.MethodsIn PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) computed tomographic angiography patients, a core laboratory assessed prevalence of CAD (nonobstructive 1% to 49% left main or 1% to 69% stenosis any coronary artery), degree of stenosis (minimal: 1% to 29%; mild: 30% to 49%; or moderate: 50% to 69%), high-risk plaque (HRP) features (positive remodeling, low-attenuation plaque, and napkin-ring sign), segment involvement score (SIS), and coronary artery calcium (CAC). The primary end point was an adjudicated composite of unstable angina pectoris, nonfatal myocardial infarction, and death. Cox regression analysis determined independent predictors in nonobstructive CAD.ResultsOf 2,890 patients (age 61.7 years, 46% women) with any CAD, 90.4% (n = 2,614) had nonobstructive CAD (mean age 61.6 yrs, 46% women, atherosclerotic cardiovascular disease [ASCVD] risk 16.2%). Composite events were independently predicted by ASCVD risk (hazard ratio [HR]: 1.03; p = 0.001), degree of stenosis (30% to 69%; HR: 1.91; p = 0.011), and presence of ≥2 HRP features (HR: 2.40; p = 0.008). Addition of ≥2 HRP features to: 1) ASCVD and CAC; 2) ASCVD and SIS; or 3) ASCVD and degree of stenosis resulted in a statistically significant improvement in model fit (p = 0.0036; p = 0.0176; and p = 0.0318; respectively). Patients with ASCVD ≥7.5%, any HRP, and mild/moderate stenosis had significantly higher event rates than those who did not meet those criteria (3.0% vs. 6.2%; p = 0.007).ConclusionsAdvanced coronary plaque features have incremental value over total plaque burden for the discrimination of clinical events in low-risk stable chest pain patients with nonobstructive CAD. This may be a first step to improve prevention in this cohort with the highest absolute risk for CV events.     

Survival of Patients With Angina Pectoris Undergoing Percutaneous Coronary Intervention With Intracoronary Pressure Wire Guidance

BackgroundIntracoronary pressure wire measurement of fractional flow reserve (FFR) provides decision-making guidance during percutaneous coronary intervention (PCI). However, limited data exist on the effect of FFR on long-term clinical outcomes in patients with stable angina pectoris.ObjectivesThe purpose of this study was to determine the association between the usage of FFR and all-cause mortality in patients with stable angina undergoing PCI.MethodsData was used from the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) on all patients undergoing PCI (with or without FFR guidance) for stable angina pectoris in Sweden between January 2005 and March 2016. The primary endpoint was all-cause mortality, and the secondary endpoints were stent thrombosis (ST) or restenosis and peri-procedural complications. The primary model was multilevel Cox proportional hazards regression adjusted with Kernel-based propensity score matching.ResultsIn total, 23,860 patients underwent PCI for stable angina pectoris; of these, FFR guidance was used in 3,367. After a median follow-up of 4.7 years (range 0 to 11.2 years), the FFR group had lower adjusted risk estimates for all-cause mortality (hazard ratio: 0.81; 95% confidence interval [CI]: 0.73 to 0.89; p < 0.001), and ST and restenosis (hazard ratio: 0.74; 95% CI: 0.57 to 0.96; p = 0.022). The number of peri-procedural complications did not differ between the groups (adjusted odds ratio: 0.96; 95% CI: 0.77 to 1.19; p = 0.697).ConclusionsIn this observational study, the use of FFR was associated with a lower risk of long-term mortality, ST, and restenosis in patients undergoing PCI for stable angina pectoris. This study supports the current European and American guidelines for the use of FFR during PCI and shows that intracoronary pressure wire guidance confers prognostic benefit in patients with stable angina pectoris.     

Physiological Distribution and Local Severity of Coronary Artery Disease and Outcomes After Percutaneous Coronary Intervention

ObjectivesThe aim of this study was to evaluate prognostic implications of physiological 2-dimensional disease patterns on the basis of distribution and local severity of coronary atherosclerosis determined by quantitative flow ratio (QFR) virtual pull back.BackgroundThe beneficial effect of percutaneous coronary intervention (PCI) is determined by physiological distribution and local severity of coronary atherosclerosis.MethodsThe study population included 341 patients who underwent angiographically successful PCI and post-PCI fractional flow reserve (FFR) measurement. Using pre-PCI virtual pull backs of QFR, physiological distribution was determined by pull back pressure gradient index, with a cutoff value of 0.78 to define predominant focal versus diffuse disease. Physiological local severity was assessed by instantaneous QFR gradient per unit length, with a cutoff value of ≥0.025/mm to define a major gradient. Suboptimal post-PCI physiological results were defined as both post-PCI FFR ≤0.85 and percentage FFR increase ≤15%. Clinical outcome was assessed by target vessel failure (TVF) at 2 years.ResultsQFR pull back pressure gradient index was correlated with post-PCI FFR (R = 0.423; P < 0.001), and instantaneous QFR gradient per unit length was correlated with percentage FFR increase (R = 0.370; P < 0.001). Using the 2 QFR-derived indexes, disease patterns were classified into 4 categories: predominant focal disease with and without major gradient (group 1 [n = 150] and group 2 [n = 21], respectively) and predominant diffuse disease with and without major gradient (group 3 [n = 115] and group 4 [n = 55], respectively). Proportions of suboptimal post-PCI physiological results were significantly different according to the 4 disease patterns (18.7%, 23.8%, 22.6%, and 56.4% from group 1 to group 4, respectively; P < 0.001). Cumulative incidence of TVF after PCI was significantly higher in patients with predominant diffuse disease (8.1% in group 3 and 9.9% in group 4 vs 1.4% in group 1 and 0.0% in group 2; overall P = 0.024).ConclusionsBoth physiological distribution and local severity of coronary atherosclerosis could be characterized without pressure-wire pull backs, which determined post-PCI physiological results. After successful PCI, TVF risk was determined mainly by the physiological distribution of coronary atherosclerosis. (Automated Algorithm Detecting Physiologic Major Stenosis and Its Relationship With Post-PCI Clinical Outcomes [Algorithm-PCI], NCT04304677; Influence of FFR on the Clinical Outcome After Percutaneous Coronary Intervention [PERSPECTIVE], NCT01873560)     

AI Evaluation of Stenosis on Coronary CTA,Comparison With Quantitative Coronary Angiography and Fractional Flow Reserve: A CREDENCE Trial Substudy

BackgroundClinical reads of coronary computed tomography angiography (CTA), especially by less experienced readers, may result in overestimation of coronary artery disease stenosis severity compared with expert interpretation. Artificial intelligence (AI)-based solutions applied to coronary CTA may overcome these limitations.ObjectivesThis study compared the performance for detection and grading of coronary stenoses using artificial intelligence–enabled quantitative coronary computed tomography (AI-QCT) angiography analyses to core lab–interpreted coronary CTA, core lab quantitative coronary angiography (QCA), and invasive fractional flow reserve (FFR).MethodsCoronary CTA, FFR, and QCA data from 303 stable patients (64 ± 10 years of age, 71% male) from the CREDENCE (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia) trial were retrospectively analyzed using an Food and Drug Administration–cleared cloud-based software that performs AI-enabled coronary segmentation, lumen and vessel wall determination, plaque quantification and characterization, and stenosis determination.ResultsDisease prevalence was high, with 32.0%, 35.0%, 21.0%, and 13.0% demonstrating ≥50% stenosis in 0, 1, 2, and 3 coronary vessel territories, respectively. Average AI-QCT analysis time was 10.3 ± 2.7 minutes. AI-QCT evaluation demonstrated per-patient sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94%, 68%, 81%, 90%, and 84%, respectively, for ≥50% stenosis, and of 94%, 82%, 69%, 97%, and 86%, respectively, for detection of ≥70% stenosis. There was high correlation between stenosis detected on AI-QCT evaluation vs QCA on a per-vessel and per-patient basis (intraclass correlation coefficient = 0.73 and 0.73, respectively; P < 0.001 for both). False positive AI-QCT findings were noted in in 62 of 848 (7.3%) vessels (stenosis of ≥70% by AI-QCT and QCA of <70%); however, 41 (66.1%) of these had an FFR of <0.8.ConclusionsA novel AI-based evaluation of coronary CTA enables rapid and accurate identification and exclusion of high-grade stenosis and with close agreement to blinded, core lab–interpreted quantitative coronary angiography. (Computed TomogRaphic Evaluation of Atherosclerotic DEtermiNants of Myocardial IsChEmia [CREDENCE]; NCT02173275)     

Influence of Coronary Calcium on Diagnostic Performance of Machine Learning CT-FFR: Results From MACHINE Registry

ObjectivesThis study was conducted to investigate the influence of coronary artery calcium (CAC) score on the diagnostic performance of machine-learning–based coronary computed tomography (CT) angiography (cCTA)–derived fractional flow reserve (CT-FFR).BackgroundCT-FFR is used reliably to detect lesion-specific ischemia. Novel CT-FFR algorithms using machine-learning artificial intelligence techniques perform fast and require less complex computational fluid dynamics. Yet, influence of CAC score on diagnostic performance of the machine-learning approach has not been investigated.MethodsA total of 482 vessels from 314 patients (age 62.3 ± 9.3 years, 77% male) who underwent cCTA followed by invasive FFR were investigated from the MACHINE (Machine Learning based CT Angiography derived FFR: a Multi-center Registry) registry data. CAC scores were quantified using the Agatston convention. The diagnostic performance of CT-FFR to detect lesion-specific ischemia was assessed across all Agatston score categories (CAC 0, >0 to <100, 100 to <400, and ≥400) on a per-vessel level with invasive FFR as the reference standard.ResultsThe diagnostic accuracy of CT-FFR versus invasive FFR was superior to cCTA alone on a per-vessel level (78% vs. 60%) and per patient level (83% vs. 73%) across all Agatston score categories. No statistically significant differences in the diagnostic accuracy, sensitivity, or specificity of CT-FFR were observed across the categories. CT-FFR showed good discriminatory power in vessels with high Agatston scores (CAC ≥400) and high performance in low-to-intermediate Agatston scores (CAC >0 to <400) with a statistically significant difference in the area under the receiver-operating characteristic curve (AUC) (AUC: 0.71 [95% confidence interval (CI): 0.57 to 0.85] vs. 0.85 [95% CI: 0.82 to 0.89], p = 0.04). CT-FFR showed superior diagnostic value over cCTA in vessels with high Agatston scores (CAC ≥ 400: AUC 0.71 vs. 0.55, p = 0.04) and low-to-intermediate Agatston scores (CAC >0 to <400: AUC 0.86 vs. 0.63, p < 0.001).ConclusionsMachine-learning–based CT-FFR showed superior diagnostic performance over cCTA alone in CAC with a significant difference in the performance of CT-FFR as calcium burden/Agatston calcium score increased. (Machine Learning Based CT Angiography Derived FFR: a Multicenter, Registry [MACHINE] NCT02805621).     

CT Angiographic and Plaque Predictors of Functionally Significant Coronary Disease and Outcome Using Machine Learning

ObjectivesThe goal of this study was to investigate the association of stenosis and plaque features with myocardial ischemia and their prognostic implications.BackgroundVarious anatomic, functional, and morphological attributes of coronary artery disease (CAD) have been independently explored to define ischemia and prognosis.MethodsA total of 1,013 vessels with fractional flow reserve (FFR) measurement and available coronary computed tomography angiography were analyzed. Stenosis and plaque features of the target lesion and vessel were evaluated by an independent core laboratory. Relevant features associated with low FFR (≤0.80) were identified by using machine learning, and their predictability of 5-year risk of vessel-oriented composite outcome, including cardiac death, target vessel myocardial infarction, or target vessel revascularization, were evaluated.ResultsThe mean percent diameter stenosis and invasive FFR were 48.5 ± 17.4% and 0.81 ± 0.14, respectively. Machine learning interrogation identified 6 clusters for low FFR, and the most relevant feature from each cluster was minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index (in order of importance). These 6 features showed predictability for low FFR (area under the receiver-operating characteristic curve: 0.797). The risk of 5-year vessel-oriented composite outcome increased with every increment of the number of 6 relevant features, and it had incremental prognostic value over percent diameter stenosis and FFR (area under the receiver-operating characteristic curve: 0.706 vs. 0.611; p = 0.031).ConclusionsSix functionally relevant features, including minimum lumen area, percent atheroma volume, fibrofatty and necrotic core volume, plaque volume, proximal left anterior descending coronary artery lesion, and remodeling index, help define the presence of myocardial ischemia and provide better prognostication in patients with CAD. (CCTA-FFR Registry for Risk Prediction; NCT04037163)     

Blinded Physiological Assessment of Residual Ischemia After Successful Angiographic Percutaneous Coronary Intervention: The DEFINE PCI Study

ObjectivesThis study sought to evaluate the incidence and causes of an abnormal instantaneous wave-free ratio (iFR) after angiographically successful percutaneous coronary intervention (PCI).BackgroundImpaired coronary physiology as assessed by fractional flow reserve is present in some patients after PCI and is prognostically relevant.MethodsDEFINE PCI (Physiologic Assessment of Coronary Stenosis Following PCI) was a multicenter, prospective, observational study in which a blinded iFR pull back was performed after angiographically successful PCI in 562 vessels in 500 patients. Inclusion criteria were angina with either multivessel or multilesion coronary artery disease with an abnormal baseline iFR. The primary endpoint of the study was the rate of residual ischemia after operator-assessed angiographically successful PCI, defined as an iFR <0.90. The causes of impaired iFR were categorized as stent related, untreated proximal or distal focal stenosis, or diffuse atherosclerosis.ResultsAn average of 1.1 vessels per patient had abnormal baseline iFRs, with a mean value of 0.69 ± 0.22, which improved to 0.93 ± 0.07 post-PCI. Residual ischemia after angiographically successful PCI was present in 112 patients (24.0%), with a mean iFR in that population of 0.84 ± 0.06 (range 0.60 to 0.89). Among patients with impaired post-PCI iFRs, 81.6% had untreated focal stenoses that were angiographically inapparent, and 18.4% had diffuse disease. Among the focal lesions, 38.4% were located within the stent segment, while 31.5% were proximal and 30.1% were distal to the stent. Post-PCI vessel angiographic diameter stenosis was not a predictor of impaired post-procedural iFR.ConclusionsBlinded post-PCI physiological assessment detected residual ischemia in nearly 1 in 4 patients after coronary stenting despite an operator-determined angiographically successful result. Most cases of residual ischemia were due to inapparent focal lesions potentially amenable to treatment with additional PCI. (Physiologic Assessment of Coronary Stenosis Following PCI [DEFINE PCI]; NCT03084367)     

Superior Risk Stratification With Coronary Computed Tomography Angiography Using a Comprehensive Atherosclerotic Risk Score

ObjectivesThis study was designed to assess the prognostic value of a new comprehensive coronary computed tomography angiography (CTA) score compared with the stenosis severity component of the Coronary Artery Disease-Reporting and Data System (CAD-RADS).BackgroundCurrent risk assessment with coronary CTA is mainly focused on maximal stenosis severity. Integration of plaque extent, location, and composition in a comprehensive model may improve risk stratification.MethodsA total of 2,134 patients with suspected but without known CAD were included. The predictive value of the comprehensive CTA score (ranging from 0 to 42 and divided into 3 groups: 0 to 5, 6 to 20, and >20) was compared with the CAD-RADS combined into 3 groups (0% to 30%, 30% to 70% and ≥70% stenosis). Its predictive performance was internally and externally validated (using the 5-year follow-up dataset of the CONFIRM [Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter Registry], n = 1,971).ResultsThe mean age of patients was 55 ± 13 years, mean follow-up 3.6 ± 2.8 years, and 130 events (myocardial infarction or death) occurred. The new, comprehensive CTA score showed strong and independent predictive value using the Cox proportional hazard analysis. A model including clinical variables plus comprehensive CTA score showed better discrimination of events compared with a model consisting of clinical variables plus CAD-RADS (0.768 vs. 0.742, p = 0.001). Also, the comprehensive CTA score correctly reclassified a significant proportion of patients compared with the CAD-RADS (net reclassification improvement 12.4%, p < 0.001). Good predictive accuracy was reproduced in the external validation cohort.ConclusionsThe new comprehensive CTA score provides better discrimination and reclassification of events compared with the CAD-RADS score based on stenosis severity only. The score retained similar prognostic accuracy when externally validated. Anatomic risk scores can be improved with the addition of extent, location, and compositional measures of atherosclerotic plaque. (Comprehensive CTA risk score calculator is available at: http://18.224.14.19/calcApp/)