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 Value of Computed Tomography-Derived Fractional Flow Reserve Comparison With Myocardial Perfusion Imaging

ObjectivesThe aim of this study was to compare the incremental prognostic value of coronary computed tomography (CT) angiography (CCTA)-derived machine learning fractional flow reserve CT (ML-FFRct) versus that of ischemia detected on single-photon emission-computed tomography (SPECT) myocardial perfusion imaging (MPI) on incident cardiovascular outcomes.BackgroundSPECT MPI and ML-FFRct are noninvasive tools that can assess the hemodynamic significance of coronary atherosclerotic disease.MethodsWe studied a retrospective cohort of consecutive patients who underwent clinically indicated CCTA and SPECT MPI. ML-FFRct was computed using a ML prototype. The primary outcome was all-cause mortality and nonfatal myocardial infarction (D/MI), and the secondary outcome was D/MI and unplanned revascularization, percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) occurring more than 90 days postimaging. Multiple nested multivariate cox regression was used to model a scenario wherein an initial anatomical assessment was followed by a functional assessment.ResultsA total of 471 patients (mean age: 64 ± 13 year; 53% males) were included. Comorbidities were prevalent (78% hypertension, 66% diabetes, 81% dyslipidemia). ML-FFRct was <0.8 in at least 1 proximal/midsegment was present in 41.6% of patients, and ischemia on MPI was present in 13.8%. After a median follow-up of 18 months, 7% of patients (n = 33) experienced D/MI. On multivariate Cox proportional analysis, the presence of ischemia on MPI but not ML-FFRct significantly predicted D/MI (HR: 2.3; 95% CI: 1.0-5.0; P = 0.047; or HR: 0.7; 95% CI: 0.3-1.4; P = 0.306 respectively) when added to CCTA obstructive stenosis. Furthermore, the model with SPECT ischemia had higher global chi-square result and significantly improved reclassification. Results were similar using the secondary outcome and on several sensitivity analyses.ConclusionsIn a high-risk patient cohort, SPECT MPI but not ML-FFRct adds independent and incremental prognostic information to CCTA-based anatomical assessment and clinical risk factors in predicting incident outcomes.     

Utilization and Outcomes of Measuring Fractional Flow Reserve in Patients With Stable Ischemic Heart Disease

BackgroundThe use and clinical outcomes of fractional flow reserve (FFR) measurement in patients with stable ischemic heart disease (SIHD) are uncertain, as prior studies have been based on selected populations.ObjectivesThis study sought to evaluate contemporary, real-world patterns of FFR use and its effect on outcomes among unselected patients with SIHD and angiographically intermediate stenoses.MethodsThe authors used data from the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program to analyze patients who underwent coronary angiography between January 1, 2009, and September 30, 2017, and had SIHD with angiographically intermediate disease (40% to 69% diameter stenosis on visual inspection). The authors documented trends in FFR utilization and evaluated predictors using generalized mixed models. They applied Cox proportional hazards models to determine the association between an FFR-guided revascularization strategy and all-cause mortality at 1 year.ResultsA total of 17,989 patients at 66 sites were included. The rate of FFR use gradually increased from 14.8% to 18.5% among all patients with intermediate lesions, and from 44% to 75% among patients who underwent percutaneous coronary intervention. One-year mortality was 2.8% in the FFR group and 5.9% in the angiography-only group (p < 0.0001). After adjustment for patient, site-level, and procedural factors, FFR-guided revascularization was associated with a 43% lower risk of mortality at 1 year compared with angiography-only revascularization (hazard ratio: 0.57; 95% confidence interval: 0.45 to 0.71; p < 0.0001).ConclusionsIn patients with SIHD and angiographically intermediate stenoses, use of FFR has slowly risen, and was associated with significantly lower 1-year mortality.     

Optical Coherence Tomography Fractional Flow Reserve and Cardiovascular Outcomes in Patients With Acute Coronary Syndrome

BackgroundOptical coherence tomography–derived fractional flow reserve (OCT-FFR) correlates strongly with wire-based FFR; however, its clinical significance remains uncertain.ObjectivesThis study sought to investigate the relationship between post–percutaneous coronary intervention (PCI) OCT-FFR and long-term clinical outcomes in acute coronary syndrome (ACS).MethodsThis retrospective, multicenter, observational cohort study included consecutive patients with ACS who underwent OCT-guided emergency PCI. We analyzed post-PCI OCT images and calculated OCT-FFR to identify independent factors associated with target vessel failure (TVF) after PCI.ResultsAmong 364 enrolled patients, 54 experienced TVF during a median follow-up of 36 (IQR: 26-48) months. Vessel-level OCT-FFR was significantly lower in the TVF group than in the non-TVF group (0.87 vs 0.94; P < 0.001). In the multivariable Cox regression analysis, low vessel-level OCT-FFR (HR per 0.1 increase: 0.38; 95% CI: 0.29-0.49; P < 0.001) and thin-cap fibroatheroma in the nonculprit lesion were independently associated with TVF. The TVF rate of vessels with both low vessel-level OCT-FFR (<0.90) and thin-cap fibroatheroma in the nonculprit lesion was 8.1 times higher than that of all other vessels (69.3% vs 12.4%; HR: 8.13; 95% CI: 4.33-15.25; log-rank P < 0.001). Furthermore, adding vessel-level OCT-FFR to baseline characteristics and post-PCI OCT findings improved discriminatory and reclassification ability in identifying patients with subsequent TVF.ConclusionsVessel-level OCT-FFR was an independent factor associated with TVF after PCI in patients with ACS. Adding the OCT-FFR measurement to post-PCI OCT findings may enable better discrimination of patients with subsequent TVF after PCI for ACS. (Relationship between Intracoronary Optical Coherence Tomography Derived Virtual Fractional Flow Reserve and cardiovascular outcome on Acute coronary syndrome; UMIN000043858)     

Dynamic Stress Computed Tomography Perfusion With a Whole-Heart Coverage Scanner in Addition to Coronary Computed Tomography Angiography and Fractional Flow Reserve Computed Tomography Derived

ObjectivesThe aims of the study were to test the diagnostic accuracy of integrated evaluation of dynamic myocardial computed tomography perfusion (CTP) on top of coronary computed tomography angiography (cCTA) plus fractional flow reserve computed tomography derived (FFR_CT) by using a whole-heart coverage computed tomography (CT) scanner as compared with clinically indicated invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR).BackgroundRecently, new techniques such as dynamic stress computed tomography perfusion (stress-CTP) emerged as potential strategies to combine anatomical and functional evaluation in a one-shot scan. However, previous experiences with this technique were associated with high radiation exposure.MethodsEighty-five consecutive symptomatic patients scheduled for ICA were prospectively enrolled. All patients underwent rest cCTA followed by stress dynamic CTP with a whole-heart coverage CT scanner (Revolution CT, GE Healthcare, Milwaukee, Wisconsin). FFR_CT was also measured by using the rest cCTA dataset. The diagnostic accuracy to detect functionally significant coronary artery disease (CAD) in a vessel-based model of cCTA alone, cCTA+FFR_CT, cCTA+CTP, or cCTA+FFR_CT+CTP were assessed and compared by using ICA and invasive FFR as reference. The overall effective dose of dynamic CTP was also measured.ResultsThe prevalence of obstructive CAD and functionally significant CAD was 77% and 57%, respectively. The sensitivity and specificity of cCTA alone, cCTA+FFR_CT, and cCTA+CTP were 83% and 66%, 86% and 75%, and 73% and 86%, respectively. Both the addition of FFR_CT and CTP improves the area under the curve (AUC: 0.876 and 0.878, respectively) as compared with cCTA alone (0.826; p < 0.05). The sequential strategy of cCTA+FFR_CT+CTP showed the highest AUC (0.919; p < 0.05) as compared with all other strategies. The mean effective radiation dose (ED) for cCTA and stress CTP was 2.8 ± 1.2 mSv and 5.3 ± 0.7 mSv, respectively.ConclusionsThe addition of dynamic stress CTP on top of cCTA and FFR_CT provides additional diagnostic accuracy with acceptable radiation exposure.     

Sex Differences in Coronary Computed Tomography Angiography–Derived Fractional Flow Reserve: Lessons From ADVANCE

ObjectivesThis study is to determine the management and clinical outcomes of patients investigated with coronary computed tomography angiography (CCTA)–derived fractional flow reserve (FFR_CT) according to sex.BackgroundWomen are underdiagnosed with conventional ischemia testing, have lower rates of obstructive coronary artery disease (CAD) at invasive coronary angiography (ICA), yet higher mortality compared to men. Whether FFR_CT improves sex-based patient management decisions compared to CCTA alone is unknown.MethodsSubjects with symptoms and CAD on CCTA were enrolled (2015 to 2017). Demographics, symptom status, CCTA anatomy, coronary volume to myocardial mass ratio (V/M), lowest FFR_CT values, and management plans were captured. Endpoints included reclassification rate between CCTA and FFR_CT management plans, incidence of ICA demonstrating obstructive CAD (≥50% stenosis) and revascularization rates.ResultsA total of 4,737 patients (n = 1,603 females, 33.8%) underwent CCTA and FFR_CT. Women were older (age 68 ± 10 years vs. 65 ± 10 years; p < 0.0001) with more atypical symptoms (41.5% vs. 33.9%; p < 0.0001). Women had less obstructive CAD (65.4% vs. 74.7%; p < 0.0001) at CCTA, higher FFR_CT (0.76 ± 0.10 vs. 0.73 ± 0.10; p < 0.0001), and lower likelihood of positive FFR_CT ≤ 0.80 for the same degree stenosis (p < 0.0001). A positive FFR_CT ≤0.80 resulted in equal referral to ICA (n = 510 [54.5%] vs. n = 1,249 [56.5%]; p = 0.31), but more nonobstructive CAD (n = 208 [32.1%] vs. n = 354 [24.5%]; p = 0.0003) and less revascularization (n = 294 [31.4%] vs. n = 800 [36.2%]; p < 0.0001) in women, unless the FFR_CT was ≤0.75 where revascularization rates were similar (n = 253 [41.9%] vs. n = 715 [46.4%]; p = 0.06). Women have a higher V/M ratio (26.17 ± 7.58 mm³/g vs. 24.76 ± 7.22 mm³/g; p < 0.0001) that is associated with higher FFR_CT independent of degree stenosis (p < 0.001). Predictors of revascularization included stenosis severity, FFR_CT, symptoms, and V/M ratio (p < 0.001) but not female sex (p = 0.284).ConclusionsFFR_CT differs between the sexes, as women have a higher FFR_CT for the same degree of stenosis. In FFR_CT-positive CAD, women have less obstructive CAD at ICA and less revascularization, which is associated with higher V/M ratio. The findings suggest that CAD and FFR_CT variations by sex need specific interpretation as these differences may affect therapeutic decision making and clinical outcomes. (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care [ADVANCE]; NCT02499679)     

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)     

Cardiac Magnetic Resonance for Evaluating Nonculprit Lesions After Myocardial Infarction: Comparison With Fractional Flow Reserve

ObjectivesThis study sought to determine the agreement between cardiac magnetic resonance (CMR) imaging and invasive measurements of fractional flow reserve (FFR) in the evaluation of nonculprit lesions after ST-segment elevation myocardial infarction (STEMI). In addition, we investigated whether fully quantitative analysis of myocardial perfusion is superior to semiquantitative and visual analysis.BackgroundThe agreement between CMR and FFR in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease is unknown.MethodsSeventy-seven patients with STEMI with at least 1 intermediate (diameter stenosis 50% to 90%) nonculprit lesion underwent CMR and invasive coronary angiography in conjunction with FFR measurements at 1 month after primary intervention. The imaging protocol included stress and rest perfusion, cine imaging, and late gadolinium enhancement. Fully quantitative, semiquantitative, and visual analysis of myocardial perfusion were compared against a reference of FFR. Hemodynamically obstructive was defined as FFR ≤0.80.ResultsHemodynamically obstructive nonculprit lesions were present in 31 (40%) patients. Visual analysis displayed an area under the curve (AUC) of 0.74 (95% confidence interval [CI]: 0.62 to 0.83), with a sensitivity of 73% and a specificity of 70%. For semiquantitative analysis, the relative upslope of the stress signal intensity time curve and the relative upslope derived myocardial flow reserve had respective AUCs of 0.66 (95% CI: 0.54 to 0.77) and 0.71 (95% CI: 0.59 to 0.81). Fully quantitative analysis did not augment diagnostic performance (all p > 0.05). Stress myocardial blood flow displayed an AUC of 0.76 (95% CI: 0.64 to 0.85), with a sensitivity of 69% and a specificity of 77%. Similarly, MFR displayed an AUC of 0.82 (95% CI: 0.71 to 0.90), with a sensitivity of 82% and a specificity of 71%.ConclusionsCMR and FFR have moderate-good agreement in the evaluation of nonculprit lesions in patients with STEMI with multivessel disease. Fully quantitative, semiquantitative, and visual analysis yield similar diagnostic performance.     

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)     

Myocardial Flow Reserve and Coronary Calcification in Prognosis of Patients With Suspected Coronary Artery Disease

ObjectivesThe aim of this analysis is to examine the incremental prognostic value of coronary artery calcium (CAC) score and myocardial flow reserve (MFR) in patients with suspected coronary artery disease (CAD) undergoing positron emission tomography (PET) myocardial perfusion imaging (MPI).BackgroundAdvances in cardiac PET and computed tomography imaging enabled the simultaneous acquisition of anatomic and physiological data for patients suspected of CAD.MethodsConsecutive patients who underwent PET MPI and CAC score calculation at King Abdulaziz Cardiac Center, Riyadh, Saudi Arabia, between May 2011 and May 2018 were included in the study. MPI and CAC images were obtained in the same setting. The primary endpoint of the study was a composite of cardiac death and nonfatal myocardial infarction. Cox proportional hazard regression was used to assess the incremental prognostic value of CAC and MFR by sequentially adding the variables to a model that included clinical and PET variables.ResultsA total of 4,008 patients (mean age 59.7 ± 11.6 years, 55% women) were included in the analysis. Risk factors were prevalent (77.6% hypertension, 58.1% diabetes). In total, 35.9% of the cohort had CAC of 0, 16.5% had CAC ≥400, and 43.9% had MFR <2. Over a median follow up of 1.9 years, 130 (3.2%) patients had cardiac death/nonfatal myocardial infarction. CAC and MFR score added incremental prognostic value over clinical and perfusion variables (base model: c-index 0.8137; Akaike information criterion [AIC]: 1,865.877; p = 0.0011; CAC model: c-index = 0.8330; AIC: 1,850.810; p = 0.045 vs. base model; MFR model: c-index = 0.8279; AIC: 1,859.235; p = 0.024). Combining CAC and MFR did not enhance risk prediction (c-index = 0.8435; AIC: 1,846.334; p = 0.074 vs. MFR model; p = 0.21 vs. CAC model.)ConclusionsIn this large cohort of patients referred for PET MPI, both CAC and MFR independently added incremental prognostic value over clinical and MPI variables. Although combining both may have synergetic prognostic effect, this relation was not shown in multivariable model of this analysis.     

Thrombotic Risk and Cardiovascular Events in Patients With Revascularization Deferral After Fractional Flow Reserve Assessment

ObjectivesThe aim of this study was to evaluate the impact of thrombotic risk on the occurrence of cardiovascular events in patients with coronary artery disease with deferred revascularization after fractional flow reserve (FFR) measurements.BackgroundDeferral of revascularization on the basis of FFR is generally considered to be safe, but after deferral, some patients have cardiovascular events over time.MethodsFrom J-CONFIRM registry (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry), 1,263 patients with deferral of revascularization on the basis of FFR were evaluated. The association between thrombotic risk as assessed by CREDO-Kyoto (Coronary Revascularization Demonstrating Outcome Study in Kyoto) thrombotic score and 5-year target vessel failure (TVF) and major adverse cardiac and cerebrovascular events (MACCE) was investigated.ResultsFFR and high thrombotic risk (HTR) were associated with increased risk for 5-year TVF (FFR per 0.01-unit decrease: HR: 1.08; 95% CI: 1.05-1.11; P < 0.001; HTR: HR: 2.16; 95% CI: 1.37-3.39; P < 0.001) and MACCE (FFR per 0.01-unit decrease: HR: 1.05; 95% CI: 1.02-1.06; P < 0.001; HTR: HR: 2.11; 95% CI: 1.56-2.84; P = 0.001). Patients with HTR had higher risk for 5-year TVF (HR: 2.30; 95% CI: 1.45-3.66; P < 0.001) and MACCE (HR: 2.34; 95% CI: 1.75-3.13; P < 0.001) than those without HTR, even when they had negative FFR.ConclusionsAssessment of thrombotic risk provides additional prognostic value to FFR in predicting 5-year TVF and MACCE in patients with deferral of revascularization after FFR measurements. (Long-Term Outcomes of Japanese Patients With Deferral of Coronary Intervention Based on Fractional Flow Reserve in Multicenter Registry; UMIN000014473)     

Impaired Coronary Vasodilator Reserve and Adverse Prognosis in Patients With Systemic Inflammatory Disorders

ObjectivesThe purpose of this study was to evaluate the prognostic value of quantitative myocardial blood flow (MBF) and myocardial flow reserve (MFR), reflecting the integrated effects of diffuse atherosclerosis and microvascular dysfunction in patients with systemic inflammatory disorders.BackgroundRheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and psoriasis (PsO) are common inflammatory conditions with excess cardiovascular (CV) risk compared to the general population. Systemic inflammation perturbs endothelial function and has been linked to coronary vasomotor dysfunction. However, the prognostic significance of this vascular dysfunction is not known.MethodsThis was a retrospective study of patients with RA, SLE, and PsO undergoing clinically indicated rest and stress myocardial perfusion positron emission tomography (PET). Patients with an abnormal myocardial perfusion study or left ventricular dysfunction were excluded. MFR was calculated as the ratio of myocardial blood flow (MBF, ml/min/g) at peak stress compared to that at rest.ResultsAmong the 198 patients (median age: 65 years; 80% female), 20.7% had SLE, 31.8% had PsO, and 47.5% had RA. There were no differences in mean MFR between these conditions. Over a median follow-up of 7.8 years, there were 51 deaths and 63 major adverse cardiovascular events (MACE). Patients in the lowest tertile (MFR <1.65) had higher all-cause mortality than the highest tertile, which remained significant after adjusting for age, sex, and the pre-test clinical risk score (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.05 to 5.4; p = 0.038). Similarly, compared to the highest MFR tertile, those in the lowest tertile had a lower MACE-free survival after adjusting for age, sex, and the pre-test clinical risk score (HR: 3.6; 95% CI: 1.7 to 7.6; p = 0.001).ConclusionsIn patients with systemic inflammatory disorders, impaired coronary vasodilator reserve was associated with worse cardiovascular outcomes and all-cause mortality.     

Differences in Progression to Obstructive Lesions per High-Risk Plaque Features and Plaque Volumes With CCTA

ObjectivesThis study explored whether the pattern of nonobstructive lesion progression into obstructive lesions would differ according to the presence of high-risk plaque (HRP).BackgroundIt is still debatable whether HRP simply represents a certain phase during the natural history of coronary atherosclerotic plaques or if disease progression would differ according to the presence of HRP.MethodsPatients with nonobstructive coronary artery disease, defined as percent diameter stenosis (%DS) <50%, were enrolled from a prospective, multinational registry of consecutive patients who underwent serial coronary computed tomography angiography at an interscan interval of ≥2 years. HRP was defined as lesions with ≥2 features of positive remodeling, spotty calcification, or low-attenuation plaque. Quantitative total and compositional percent atheroma volume (PAV) at baseline and annualized PAV change were compared between non-HRP and HRP lesions.ResultsA total of 3,049 nonobstructive lesions were identified from 1,297 patients (mean age 60.3 ± 9.3 years; 56.8% men). There were 2,624 non-HRP and 425 HRP lesions. HRP lesions had a greater total PAV and all noncalcified components of PAV and %DS at baseline compared with non-HRP lesions. However, the annualized total PAV changes were greater in non-HRP lesions than in HRP lesions. On multivariate analysis adjusted for clinical risk factors, drug use, change in lipid level, total PAV, %DS, and HRP, only the baseline total PAV and %DS independently predicted the development of obstructive lesions (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07, and HR: 1.07; 95% CI: 1.04 to 1.10, respectively, all p < 0.05), whereas the presence of HRP did not (p > 0.05).ConclusionsThe pattern of individual coronary atherosclerotic plaque progression differed according to the presence of HRP. Baseline PAV, not the presence of HRP features, was the most important predictor of lesions developing into obstructive lesions. (Progression of Atherosclerotic Plaque Determined By Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)     

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.     

Plaque Rupture,Compared With Plaque Erosion,Is Associated With a Higher Level of Pancoronary Inflammation

ObjectivesThe aim of this study was to compare the level of coronary inflammation between plaque rupture and plaque erosion using pericoronary adipose tissue (PCAT) attenuation.BackgroundVascular inflammation plays a key role in plaque rupture, while the role of inflammation in plaque erosion remains less well defined. PCAT attenuation determined using computed tomography has emerged as a marker specific for coronary artery inflammation.MethodsPatients with non–ST-segment elevation acute coronary syndromes who underwent preintervention coronary computed tomographic angiography and optical coherence tomographic culprit lesion imaging were enrolled. PCAT attenuation was measured around the culprit lesion and in the proximal 40 mm of all coronary arteries.ResultsAmong 198 patients, plaque rupture was the underlying mechanism in 107 (54.0%) and plaque erosion in 91 (46.0%). Plaque rupture had higher PCAT attenuation than plaque erosion both at the culprit plaque level (?65.8 ± 7.5 HU vs ?69.5 ± 11.4 HU; P = 0.010) and at the culprit vessel level (?67.1 ± 7.1 HU vs ?69.6 ± 8.2 HU; P = 0.024). The mean PCAT attenuation of all 3 coronary arteries was also significantly higher in patients with plaque rupture than in plaque erosion, indicating a higher level of inflammation (?67.9 ± 5.7 HU vs ?69.9 ± 6.8 HU; P = 0.030). In multivariable analysis, plaque rupture was significantly associated with high PCAT attenuation.ConclusionsPCAT attenuation in culprit plaque, culprit vessel, and all 3 coronary arteries was higher in plaque rupture than in plaque erosion. The results suggest that pancoronary inflammation plays a more significant role in plaque rupture than in plaque erosion. (Massachusetts General Hospital and Tsuchiura Kyodo General Hospital Coronary Imaging Collaboration; NCT04523194)     

Fractional Flow Reserve or Optical Coherence Tomography to Guide Management of Angiographically Intermediate Coronary Stenosis: A Single-Center Trial

ObjectivesThe aim of this study was to compare optical coherence tomographic (OCT) guidance and fractional flow reserve (FFR) guidance in patients with angiographically intermediate coronary lesions (AICLs) in a single-center, prospective, 1:1 randomized trial.BackgroundFFR and OCT imaging may help both in the assessment of AICLs and in percutaneous coronary intervention optimization.MethodsPatients with AICLs were randomized to FFR or OCT imaging. In the FFR arm, PCI was performed if FFR was ≤0.80. In the OCT imaging arm, PCI was performed if area stenosis was ≥75% or 50% to 75% with minimal luminal area <2.5 mm² or plaque rupture. Angina (evaluated using the Seattle Angina Questionnaire), major adverse cardiac events, and cost were assessed at the end of follow-up. The pre-defined primary endpoint was the composite of major adverse cardiac events or significant angina (defined as Seattle Angina Questionnaire frequency scale score <90) at 13 months.ResultsA total of 350 patients (with 446 AICLs) were enrolled (176 randomized to FFR and 174 to OCT imaging). The primary endpoint of major adverse cardiac events or significant angina at 13 months occurred in 14.8% of patients in the FFR arm and in 8.0% in the OCT imaging arm (p = 0.048). This result was driven by a statistically nonsignificant lower occurrence of all primary endpoint components. Up to 13 months, the rate of medically managed patients was significantly higher (p < 0.001) and total cost significantly lower (p < 0.001) with FFR in comparison with OCT imaging.ConclusionsIn patients with AICLs, OCT guidance is associated with lower occurrence of the composite of major adverse cardiac events or significant angina. FFR guidance is associated with a higher rate of medical management and lower costs. FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty [FORZA]; NCT01824030)     

Stenting “Vulnerable” But Fractional Flow Reserve–Negative Lesions: Potential Statistical Limitations of Ongoing and Future Trials

Can imaging provide sufficient risk stratification to warrant revascularization of a stable plaque with negative fractional flow reserve (FFR)? Prophylactic stenting could at best be applied selectively since the composite group of FFR-negative lesions has a death or myocardial infarction rate of approximately 1%/year or less but modern stents have a rate of 2% to 3.5%/year. Because vulnerable features exist in a minority of lesions, at least 9,000 patients must be screened in order to enroll a cohort with sufficient risk. While several ongoing randomized trials are testing the concept of plaque sealing in FFR-negative lesions, preventive stenting depends on such a small effect that sample sizes to validate or refute its benefit become prohibitive. Since FFR provides a quantitative, straightforward, and reproducible metric of plaque vulnerability and burden without the need for or expense of additional catheter devices, intracoronary imaging cannot meaningfully guide prophylactic stenting when faced with a negative FFR.     

Fractional Flow Reserve–Based Coronary Artery Bypass Surgery: Current Evidence and Future Directions

Fractional flow reserve (FFR) provides an objective measurement of the severity of ischemia caused by coronary stenoses in downstream myocardial regions. Data from the interventional cardiology realm have suggested benefits of a FFR-guided percutaneous coronary intervention (PCI) strategy. Limited evidence is available on the use of FFR to guide coronary artery bypass grafting (CABG). The most recent data have shown that FFR might simplify CABG procedures and optimize patency of arterial grafts without any clear impact on clinical outcomes. The aim of this review was to summarize the available data on FFR-based CABG and discuss the rationale and potential consequences of a switch toward FFR-based surgical revascularization strategy.     

Association of Tube Voltage With Plaque Composition on Coronary CT Angiography: Results From PARADIGM Registry

ObjectivesThis study sought to investigate the impact of low tube voltage scanning heterogeneity of coronary luminal attenuation on plaque quantification and characterization with coronary computed tomography angiography (CCTA).BackgroundThe impact of low tube voltage and coronary luminal attenuation on quantitative coronary plaque remains uncertain.MethodsA total of 1,236 consecutive patients (age: 60 ± 9 years; 41% female) who underwent serial CCTA at an interval of ≥2 years were included from an international registry. Patients with prior revascularization or nonanalyzable coronary CTAs were excluded. Total coronary plaque volume was assessed and subclassified based on specific Hounsfield unit (HU) threshold: necrotic core, fibrofatty plaque, and fibrous plaque and dense calcium. Luminal attenuation was measured in the aorta.ResultsWith increasing luminal HU (<350, 350-500, and >500 HU), percent calcified plaque was increased (16%, 27%, and 40% in the median; P < 0.001), and fibrofatty plaque (26%, 13%, and 4%; P < 0.001) and necrotic core (1.6%, 0.3%, and 0.0%; P < 0.001) were decreased. Higher tube voltage scanning (80, 100, and 120 kV) resulted in decreasing luminal attenuation (689 ± 135, 497 ± 89, and 391 ± 73 HU; P < 0.001) and calcified plaque volume (59%, 34%, and 23%; P < 0.001) and increased fibrofatty plaque (3%, 9%, and 18%; P < 0.001) and necrotic core (0.2%, 0.1%, and 0.6%; P < 0.001). Mediation analysis showed that the impact of 100 kV on plaque composition, compared with 120 kV, was primarily caused by an indirect effect through blood pool attenuation. Tube voltage scanning of 80 kV maintained a direct effect on fibrofatty plaque and necrotic core in addition to an indirect effect through the luminal attenuation.ConclusionsLow tube voltage usage affected plaque morphology, mainly through an increase in luminal HU with a resultant increase in calcified plaque and a reduction in fibrofatty and necrotic core. These findings should be considered as CCTA-based plaque measures are being used to guide medical management and, in particular, when being used as a measure of treatment response. (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging [PARADIGM]; NCT02803411)