FFR- Versus Angiography-Guided Revascularization for Nonculprit Stenosis in STEMI and Multivessel Disease: A Network Meta-Analysis

ObjectivesThe aim of this study was to examine the efficacy and safety of fractional flow reserve (FFR)–guided versus angiography-guided approaches for nonculprit stenosis among patients with acute ST-segment elevation myocardial infarction (STEMI) and multivessel disease.BackgroundThe optimal strategy to guide revascularization of nonculprit stenosis among patients with STEMI and multivessel disease remains uncertain.MethodsElectronic databases were searched for randomized trials evaluating the outcomes of culprit-only revascularization, angiography-guided complete revascularization (CR), or FFR-guided CR. A pairwise meta-analysis comparing CR versus culprit-only revascularization and a network meta-analysis comparing the different revascularization techniques were conducted. The primary outcome was major adverse cardiac events (MACE).ResultsThe analysis included 11 trials with 8,195 patients. CR (ie, angiography-guided or FFR-guided CR) was associated with a lower incidence of MACE (odds ratio [OR]: 0.46; 95% CI: 0.35 to 0.59), cardiovascular mortality (OR: 0.63; 95% CI: 0.41 to 0.98), recurrent myocardial infarction (OR: 0.67; 95% CI: 0.48 to 0.95), and repeat ischemia-driven revascularization (OR: 0.26; 95% CI: 0.19 to 0.35). Network meta-analysis demonstrated that the incidence of MACE was lower with both angiography-guided CR (OR: 0.43; 95% CI: 0.31 to 0.58) and FFR-guided CR (OR: 0.52; 95% CI: 0.35 to 0.78) compared with a culprit-only approach, while there was no difference in risk for MACE between angiography-guided and FFR-guided CR (OR: 0.81; 95% CI: 0.51 to 1.29).ConclusionsAmong patients with STEMI and multivessel disease, CR, with angiographic or FFR guidance for nonculprit stenosis, was associated with lower incidence of adverse events compared with culprit-only revascularization. FFR-guided CR was not superior to angiography-guided CR in reducing the incidence of adverse events. Future studies investigating other tools to risk-stratify nonculprit stenoses are encouraged.     

Differential Prognostic Value of Revascularization for Coronary Stenosis With Intermediate FFR by Coronary Flow Reserve

ObjectivesThe authors sought to evaluate comparative prognosis between deferred versus performed percutaneous coronary intervention (PCI) according to coronary flow reserve (CFR) values of patients with intermediate fractional flow reserve (FFR).BackgroundFor coronary stenosis with intermediate FFR, the prognostic value of PCI remains controversial. The prognostic impact of PCI may be different according to CFR in patients with intermediate FFR.MethodsFrom the ILIAS Registry (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry, N = 2,322), 400 patients (412 vessels) with intermediate FFR (0.75-0.80) were selected. Patients were stratified into preserved CFR (>2.0, n = 253) and depressed CFR (≤2.0, n = 147) cohorts. Per-vessel clinical outcomes during 5 years of follow-up were compared between deferred versus performed PCI groups in both cohorts. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization.ResultsAmong the study population, PCI was deferred for 210 patients (219 vessels, 53.2%) (deferred group) and performed for 190 patients (193 vessels, 46.8%) (performed group). The risk of TVF was comparable between the deferred and performed groups (12.8% vs 14.2%; adjusted HR: 1.403; 95% CI: 0.584-3.369; P = 0.448). When stratified by CFR, PCI was performed in 39.1% (100/261 vessels) of the preserved CFR cohort and 61.9% (93/151 vessels) of the depressed CFR cohort. Within the preserved CFR cohort, the risk of TVF did not differ significantly between the deferred and performed groups (11.0% vs 13.9%; adjusted HR: 0.770; 95% CI: 0.262-2.266; P = 0.635). However, in the depressed CFR cohort, the deferred group had a significantly higher risk of TVF than the performed group (17.2% vs 14.2%; adjusted HR: 4.932; 95% CI: 1.312-18.53; P = 0.018). A significant interaction was observed between CFR and the treatment decision (interaction P = 0.049). Results were consistent after inverse probability weighting adjustment.ConclusionsIn patients with intermediate FFR of 0.75 to 0.80, the prognostic value of PCI differed according to CFR, with a significant interaction. PCI was associated with a lower risk of TVF compared with the deferral strategy when CFR was depressed (≤2.0), but there was no difference when CFR was preserved (>2.0). CFR could be used as an additional risk stratification tool to determine treatment strategies in patients with intermediate FFR. (Inclusive Invasive Physiological Assessment in Angina Syndromes Registry [ILIAS Registry]; NCT04485234)     

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)     

Effect of Sex Difference of Coronary Microvascular Dysfunction on Long-Term Outcomes in Deferred Lesions

ObjectivesThis study investigated the sex difference of long-term cardiovascular outcomes on coronary flow reserve (CFR) and index of microcirculatory resistance (IMR) in patients with deferred coronary artery lesions.BackgroundCoronary microvascular dysfunction is associated with poorer long-term outcomes. It can be assessed by CFR and the IMR.MethodsThe study prospectively enrolled 434 patients (133 women and 301 men) and analyzed CFR, IMR, fractional flow reserve, and quantitative coronary angiography. Clinical outcomes were assessed by major adverse cardiovascular event(s) (MACE) of cardiac death, myocardial infarction, and revascularization during 5 years of follow-up. The study protocol was approved by the Institutional Review Board or Ethics Committee at each participating center, and all patients provided written informed consent. The study protocol was in accordance with the Declaration of Helsinki.ResultsWomen had milder epicardial disease compared with men (fractional flow reserve: 0.91 [interquartile range (IQR): 0.87 to 0.96] vs. 0.90 [IQR: 0.86 to 0.95]; p = 0.037). IMR was similar between the sexes, but CFR was lower in women (2.69 [IQR: 2.08 to 3.90] vs. 3.20 [IQR: 2.20 to 4.31]; p = 0.006) due to a shorter resting mean transit time, whereas hyperemic mean transit times were similar. At 5-year follow-up, MACE was significantly lower in women compared with men (1.1% vs. 5.5%; p = 0.017). Sex, diabetes mellitus, and CFR were independent predictors for MACE for all patients. The risk of MACE was significantly higher in men with low versus high CFR (hazard ratio: 4.58; 95% confidence interval: 1.85 to 11.30; p = 0.011) which was not seen in women.ConclusionsThere was no sex difference in microvascular function by IMR. CFR was lower in women due to a higher resting coronary flow; however, long-term clinical outcomes in deferred lesions were better in women compared with men. (Clinical, Physiological and Prognostic Implication of Microvascular Status; NCT02186093).     

Implicaciones pronósticas de los índices fisiológicos coronarios en pacientes con diabetes mellitus

Introduction and objectivesNo thorough investigation has been performed of the prognostic value of coronary physiological indices in patients with diabetes mellitus (DM) after coronary revascularization deferral.MethodsWe analyzed 714 patients (235 with DM) with deferred revascularization according to fractional flow reserve (> 0.80). A comprehensive physiological evaluation including coronary flow reserve (CFR), index of microcirculatory resistance, and fractional flow reserve was performed at the time of revascularization deferral. The median values of the CFR (2.88), fractional flow reserve (0.88), and index of microcirculatory resistance (17.85) were used to classify patients into high- or low-index groups. The primary outcome was the patient-oriented composite outcome (POCO) at 5 years, comprising all-cause death, any myocardial infarction, and any revascularization.ResultsCompared with the non-DM population, the DM population showed higher risk of POCO (HR, 2.49; 95%CI, 1.64-3.78; P < .001). In the DM population, the low-CFR group had a higher risk of POCO than the high-CFR group (HR, 3.22; 95%CI, 1.74-5.97; P < .001). In contrast, CFR values could not differentiate the risk of POCO in the non-DM population. There was a significant interaction between CFR and the presence of DM regarding the risk of POCO (P for interaction = .025). Independent predictors of POCO were a low CFR and family history of coronary artery disease in the DM population and percent diameter stenosis and multivessel disease in the non-DM population.ConclusionsThe association between coronary physiological indices and clinical outcomes differs according to the presence of DM. In deferred patients, CFR is the most important prognostic factor in patients with DM, but not in those without DM.     

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)     

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.     

Outcomes of Functionally Complete vs Incomplete Revascularization: Insights From the FAVOR III China Trial

BackgroundFunctional complete revascularization (FCR) after percutaneous coronary intervention (PCI) as determined by the residual functional SYNTAX score (rFSS) based on pressure wire fractional flow reserve assessment has been associated with an improved prognosis.ObjectivesThis study sought to determine the rates and clinical implications of FCR as assessed by the quantitative flow ratio (QFR), and to determine the outcomes of pre-PCI QFR guidance compared with standard angiography guidance in patients achieving and not achieving FCR after PCI.MethodsIn the randomized, sham-controlled, blinded, multicenter FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial, QFR-guided PCI reduced the 1-year rate of major adverse cardiac events (MACE) compared with angiography-guided PCI. In the present prespecified substudy, the incidence of MACE was compared according to the presence of post-PCI FCR (rFSS = 0 based on core laboratory–assessed QFR) in the QFR-guided and angiography-guided groups.ResultsAmong 3,781 patients with available rFSS assessments, 3,221 (85.2%) achieved FCR, including 88.1% after QFR guidance and 82.2% after angiography guidance (P < 0.001). Patients with FCR had a markedly lower rate of 1-year MACE compared with those with functional incomplete revascularization (FIR) (rFSS ≥1) (5.1% vs 19.7%; P < 0.001). Prognostic models including the rFSS had higher discrimination and reclassification ability than those with the anatomic residual SYNTAX score. The relative risks for 1-year MACE with QFR-guided compared with the angiography-guided lesion selection were consistent in patients achieving FCR (4.1% vs 6.3%; HR: 0.65; 95% CI: 0.47-0.88) and in those with FIR (18.7% vs 20.4%; HR: 0.90; 95% CI: 0.61-1.32) (P_interaction = 0.19).ConclusionsIn this large-scale trial, achieving FCR after PCI was associated with markedly lower 1-year rates of MACE. Compared with standard angiography guidance, QFR-guided PCI lesion selection improved the likelihood of achieving FCR and improved 1-year clinical outcomes in patients with both FCR and FIR.     

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.     

Transient vs In-Hospital Persistent Acute Kidney Injury in Patients With Acute Coronary Syndrome

BackgroundThe occurrence of acute kidney injury (AKI) among patients with acute coronary syndrome (ACS) undergoing invasive management is associated with worse outcomes. However, the prognostic implications of transient or in-hospital persistent AKI may differ.ObjectivesThe aim of this study was to evaluate the prognostic implications of transient or in-hospital persistent AKI in patients with ACS.MethodsIn the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox) trial, 203 subjects were excluded because of incomplete information or end-stage renal disease, with a study population of 8,201 patients. Transient and persistent AKI were defined as renal dysfunction no longer or still fulfilling the AKI criteria (>0.5 mg/dL or a relative >25% increase in creatinine) at discharge, respectively. Thirty-day coprimary outcomes were the out-of-hospital composite of death, myocardial infarction, or stroke (major adverse cardiovascular events [MACE]) and net adverse cardiovascular events (NACE), defined as the composite of MACE or Bleeding Academic Research Consortium type 3 or 5 bleeding.ResultsPersistent and transient AKI occurred in 750 (9.1%) and 587 (7.2%) subjects, respectively. After multivariable adjustment, compared with patients without AKI, the risk for 30-day coprimary outcomes was higher in patients with persistent AKI (MACE: adjusted HR: 2.32; 95% CI: 1.48-3.64; P < 0.001; NACE: adjusted HR: 2.29; 95% CI: 1.48-3.52; P < 0.001), driven mainly by all-cause mortality (adjusted HR: 3.43; 95% CI: 2.03-5.82; P < 0.001), whereas transient AKI was not associated with higher rates of MACE or NACE. Results remained consistent when implementing the KDIGO (Kidney Disease Improving Global Outcomes) criteria.ConclusionsAmong patients with ACS undergoing invasive management, in-hospital persistent but not transient AKI was associated with higher risk for 30-day MACE and NACE. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of Angiox [MATRIX]; NCT01433627)     

Influence of Anatomical and Clinical Characteristics on Long-Term Prognosis of FFR-Guided Deferred Coronary Lesions

ObjectivesThe aim of this study was to evaluate the clinical and anatomical features to predict the long-term outcomes in patients with fractional flow reserve (FFR)–guided deferred lesions, verified by intravascular ultrasound (IVUS).BackgroundDeferral of nonsignificant lesion by FFR is associated with a low risk of clinical events. However, the impact of combined information on clinical and anatomical factors is not well known.MethodsThe study included 459 patients with 552 intermediate lesions who had deferred revascularization on the basis of a nonischemic FFR (>0.80). Grayscale IVUS was examined simultaneously. The primary endpoint was patient-oriented composite outcome (POCO) (a composite of all-cause death, myocardial infarction, and any revascularization) during 5-year follow-up.ResultsThe rate of 5-year POCO was 9.8%. Diabetes mellitus (hazard ratio: 3.50; 95% confidence interval [CI]: 1.86 to 6.57; p < 0.001), left ventricular ejection fraction ≤40% (hazard ratio: 4.80; 95% CI: 1.57 to 14.63; p = 0.006), and positive remodeling (hazard ratio: 2.04; 95% CI: 1.03 to 4.03; p = 0.041) were independent predictors for POCO. When the lesions were classified according to the presence of the adverse clinical characteristics (diabetes, left ventricular ejection fraction ≤40%) or adverse plaque characteristics (positive remodeling, plaque burden ≥70%), the risk of POCO was incrementally increased (4.3%, 13.6%, and 21.3%, respectively; p < 0.001).ConclusionsIn patients with FFR-guided deferred lesions, 5-year clinical outcomes were excellent. Lesion-related anatomical factors from intravascular imaging as well as patient-related clinical factors could provide incremental information about future clinical risks.     

Invasive Approaches in the Management of Cocaine-Associated Non–ST-Segment Elevation Myocardial Infarction

ObjectivesThe aim of this study was to determine the impact of invasive approaches and revascularization in patients with cocaine-associated non–ST-segment elevation myocardial infarction (NSTEMI).BackgroundThe role of invasive approaches in cocaine-associated NSTEMI is uncertain.MethodsThis retrospective cohort study identified 3,735 patients with NSTEMI and history of cocaine use from the Nationwide Readmissions Database from 2016 to 2017. Invasive approaches were defined as coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). Revascularization was defined as PCI and CABG. The primary efficacy outcome was major adverse cardiac events (MACE), and the primary safety outcome was emergent revascularization. Nonadherence was identified using appropriate International Classification of Diseases-Tenth Revision codes. Two propensity-matched cohorts were generated (noninvasive vs. invasive and noninvasive vs. revascularization) through multivariate logistic regression.ResultsIn the propensity score–matched cohorts, an invasive approach (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.56 to 0.92; p = 0.008) and revascularization (HR: 0.54; 95% CI: 0.40 to 0.73; p < 0.001) (compared with a noninvasive approach) were associated with a lower rate of MACE, without an increase in emergent revascularization. On stratification, PCI and CABG individually were associated with a lower rate of MACE. Emergent revascularization was increased with PCI (HR: 1.78; 95% CI: 1.12 to 2.81; p = 0.014) but not with CABG. Nonadherent patients after PCI and CABG did not have significant difference in rate of MACE. PCI in nonadherent patients was associated with an increase in emergent revascularization (HR: 4.45; 95% CI: 2.07 to 9.57; p < 0.001).ConclusionsInvasive approaches and revascularization for cocaine-associated NSTEMI are associated with lower morbidity. A history of medical nonadherence was not associated with a difference in morbidity but was associated with an increased risk for emergent revascularization with PCI.     

2-Year Outcomes After Stenting of Lipid-Rich and Nonrich Coronary Plaques

BackgroundAutopsy studies suggest that implanting stents in lipid-rich plaque (LRP) may be associated with adverse outcomes.ObjectivesThe purpose of this study was to evaluate the association between LRP detected by near-infrared spectroscopy (NIRS) and clinical outcomes in patients with coronary artery disease treated with contemporary drug-eluting stents.MethodsIn this prospective, multicenter registry, NIRS was performed in patients undergoing coronary angiography and possible percutaneous coronary intervention (PCI). Lipid core burden index (LCBI) was calculated as the fraction of pixels with the probability of LRP >0.6 within a region of interest. MaxLCBI_4mm was defined as the maximum LCBI within any 4-mm-long segment. Major adverse cardiac events (MACE) included cardiac death, myocardial infarction, definite or probable stent thrombosis, or unplanned revascularization or rehospitalization for progressive angina or unstable angina. Events were subcategorized as culprit (treated) lesion–related, nonculprit (untreated) lesion–related, or indeterminate.ResultsAmong 1,999 patients who were enrolled in the COLOR (Chemometric Observations of Lipid Core Plaques of Interest in Native Coronary Arteries Registry), PCI was performed in 1,621 patients and MACE occurred in 18.0% of patients, of which 8.3% were culprit lesion–related, 10.7% were nonculprit lesion–related, and 3.1% were indeterminate during 2-year follow-up. Complications from NIRS imaging occurred in 9 patients (0.45%), which resulted in 1 peri-procedural myocardial infarction and 1 emergent coronary bypass. Pre-PCI NIRS imaging was obtained in 1,189 patients, and the 2-year rate of culprit lesion–related MACE was not significantly associated with maxLCBI_4mm (hazard ratio of maxLCBI_4mm per 100: 1.06; 95% confidence interval: 0.96 to 1.17; p = 0.28) after adjusting clinical and procedural factors.ConclusionsFollowing PCI with contemporary drug-eluting stents, stent implantation in NIRS-defined LRPs was not associated with increased periprocedural or late adverse outcomes compared with those without significant lipid.     

Prognostic Value of Quantitative Metrics From Positron Emission Tomography in Ischemic Heart Failure

ObjectivesThe aim of this study was to investigate the prognostic and clinical value of quantitative positron emission tomographic (PET) metrics in patients with ischemic heart failure.BackgroundAlthough myocardial flow reserve (MFR) is a strong predictor of cardiac risk in patients without heart failure, it is unknown whether quantitative PET metrics improve risk stratification in patients with ischemic heart failure.MethodsThe study included 254 patients referred for stress and rest myocardial perfusion imaging and viability testing using PET. Major adverse cardiac event(s) (MACE) consisted of death, resuscitated sudden cardiac death, heart transplantation, acute coronary syndrome, hospitalization for heart failure, and late revascularization.ResultsMACE occurred in 170 patients (67%) during a median follow-up of 3.3 years. In a multivariate Cox proportional hazards model including multiple quantitative PET metrics, only MFR predicted MACE significantly (p = 0.013). Beyond age, symptom severity, diabetes mellitus, previous myocardial infarction or revascularization, 3-vessel disease, renal insufficiency, ejection fraction, as well as presence and burden of ischemia, scar, and hibernating myocardium, MFR was strongly associated with MACE (adjusted hazard ratio per increase in MFR by 1: 0.63; 95% confidence interval: 0.45 to 0.91). Incorporation of MFR into a risk assessment model incrementally improved the prediction of MACE (likelihood ratio chi-square test [16] = 48.61 vs. chi-square test [15] = 39.20; p = 0.002).ConclusionsIn this retrospective analysis of a single-center cohort, quantitative PET metrics of myocardial blood flow all improved risk stratification in patients with ischemic heart failure. However, in a hypothesis-generating analysis, MFR appears modestly superior to the other metrics as a prognostic index.     

Ticagrelor vs Prasugrel in a Contemporary Real-World Cohort Undergoing Percutaneous Coronary Intervention

BackgroundPotent P2Y₁₂ agents such as ticagrelor and prasugrel are increasingly utilized across the clinical spectrum of patients undergoing percutaneous coronary intervention (PCI). There is a paucity of data supporting their use in a patient population inclusive of both acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) patients.ObjectivesThe authors compared the efficacy and safety of ticagrelor and prasugrel in a real-world contemporary PCI cohort.MethodsConsecutive patients undergoing PCI between 2014 and 2019 discharged on either prasugrel or ticagrelor were included from the prospectively collected institutional PCI registry. Primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularization at 1 year.ResultsOverall, 3,858 patients were included in the study (ticagrelor: n = 2,771; prasugrel: n = 1,087), and a majority (48.4%) underwent PCI in the context of CCS. Patients prescribed ticagrelor were more likely to be female, have a history of cerebrovascular disease, and have ACS presentation, while those receiving prasugrel were more likely to be White with a higher prevalence of prior revascularization. No difference in the risk of death or MI was noted across the groups (ticagrelor vs prasugrel: 3.3% vs 3.1%; HR: 0.88; 95% CI: 0.54-1.43; P = 0.59). Rates of target vessel revascularization were significantly lower in the ticagrelor cohort (9.3% vs 14.0%; adjusted HR: 0.71; 95% CI: 0.55-0.91; P = 0.007) with no differences in stroke or bleeding. The results were consistent in patients with CCS (HR: 0.84; 95% CI: 0.46-1.54) and ACS (HR: 1.18; 95% CI: 0.46-1.54), without evidence of interaction (P = 0.37), and confirmed across multivariable adjustment and propensity score stratification analysis.ConclusionsIn this contemporary patient population undergoing PCI, prasugrel and ticagrelor were associated with similar 1-year efficacy and safety.     

Identification of High-Risk Plaques Destined to Cause Acute Coronary Syndrome Using Coronary Computed Tomographic Angiography and Computational Fluid Dynamics

ObjectivesThe authors investigated the utility of noninvasive hemodynamic assessment in the identification of high-risk plaques that caused subsequent acute coronary syndrome (ACS).BackgroundACS is a critical event that impacts the prognosis of patients with coronary artery disease. However, the role of hemodynamic factors in the development of ACS is not well-known.MethodsSeventy-two patients with clearly documented ACS and available coronary computed tomographic angiography (CTA) acquired between 1 month and 2 years before the development of ACS were included. In 66 culprit and 150 nonculprit lesions as a case-control design, the presence of adverse plaque characteristics (APC) was assessed and hemodynamic parameters (fractional flow reserve derived by coronary computed tomographic angiography [FFR_CT], change in FFR_CT across the lesion [△FFR_CT], wall shear stress [WSS], and axial plaque stress) were analyzed using computational fluid dynamics. The best cut-off values for FFR_CT, △FFR_CT, WSS, and axial plaque stress were used to define the presence of adverse hemodynamic characteristics (AHC). The incremental discriminant and reclassification abilities for ACS prediction were compared among 3 models (model 1: percent diameter stenosis [%DS] and lesion length, model 2: model 1 + APC, and model 3: model 2 + AHC).ResultsThe culprit lesions showed higher %DS (55.5 ± 15.4% vs. 43.1 ± 15.0%; p < 0.001) and higher prevalence of APC (80.3% vs. 42.0%; p < 0.001) than nonculprit lesions. Regarding hemodynamic parameters, culprit lesions showed lower FFR_CT and higher △FFR_CT, WSS, and axial plaque stress than nonculprit lesions (all p values <0.01). Among the 3 models, model 3, which included hemodynamic parameters, showed the highest c-index, and better discrimination (concordance statistic [c-index] 0.789 vs. 0.747; p = 0.014) and reclassification abilities (category-free net reclassification index 0.287; p = 0.047; relative integrated discrimination improvement 0.368; p < 0.001) than model 2. Lesions with both APC and AHC showed significantly higher risk of the culprit for subsequent ACS than those with no APC/AHC (hazard ratio: 11.75; 95% confidence interval: 2.85 to 48.51; p = 0.001) and with either APC or AHC (hazard ratio: 3.22; 95% confidence interval: 1.86 to 5.55; p < 0.001).ConclusionsNoninvasive hemodynamic assessment enhanced the identification of high-risk plaques that subsequently caused ACS. The integration of noninvasive hemodynamic assessments may improve the identification of culprit lesions for future ACS. (Exploring the Mechanism of Plaque Rupture in Acute Coronary Syndrome Using Coronary CT Angiography and Computational Fluid Dynamic [EMERALD]; NCT02374775)     

Incidence and Outcomes of Acute Coronary Syndrome After Transcatheter Aortic Valve Replacement

ObjectivesThis study sought to address a knowledge gap by examining the incidence, timing, and predictors of acute coronary syndrome (ACS) after transcatheter aortic valve replacement (TAVR) in Medicare beneficiaries.BackgroundEvidence about incidence and outcomes of ACS after TAVR is scarce.MethodsWe identified Medicare patients who underwent TAVR from 2012 to 2017 and were admitted with ACS during follow-up. We compared outcomes based on the type of ACS: ST-segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI), and unstable angina. In patients with non–ST-segment elevation ACS, we compared outcomes based on the treatment strategy (invasive vs. conservative) using inverse probability weighting analysis.ResultsOut of 142,845 patients with TAVR, 6,741 patients (4.7%) were admitted with ACS after a median time of 297 days (interquartile range: 85 to 662 days), with 48% of admissions occurring within 6 months. The most common presentation was NSTEMI. Predictors of ACS were history of coronary artery disease, prior revascularization, diabetes, valve-in-TAVR, and acute kidney injury. STEMI was associated with higher 30-day and 1-year mortality compared with NSTEMI (31.4% vs. 15.5% and 51.2% vs. 41.3%, respectively; p < 0.01). Overall, 30.3% of patients with non–ST-segment elevation ACS were treated with invasive approach. On inverse probability weighting analysis, invasive approach was associated with lower adjusted long-term mortality (adjusted hazard ratio: 0.69; 95% confidence interval: 0.66 to 0.73; p < 0.01) and higher risk of repeat revascularization (adjusted hazard ratio: 1.29; 95% confidence interval: 1.16 to 1.43; p < 0.001).ConclusionsAfter TAVR, ACS is infrequent (<5%), and the most common presentation is NSTEMI. Occurrence of STEMI after TAVR is associated with a high mortality with nearly one-third of patients dying within 30 days. Optimization of care is needed for post-TAVR ACS patients and if feasible, invasive approach should be considered in these high-risk patients.     

Prognostic Value of Stress Cardiac Magnetic Resonance in Patients With Known Coronary Artery Disease

ObjectivesThis study sought to determine whether stress cardiac magnetic resonance (CMR) provides clinically relevant risk reclassification in patients with known coronary artery disease (CAD) in a multicenter setting in the United States.BackgroundDespite improvements in medical therapy and coronary revascularization, patients with previous CAD account for a disproportionately large portion of CV events and pose a challenge for noninvasive stress testing.MethodsFrom the Stress Perfusion Imaging in the United States (SPINS) registry, we identified consecutive patients with documented CAD who were referred to stress CMR for evaluation of myocardial ischemia. The primary outcome was nonfatal myocardial infarction (MI) or cardiovascular (CV) death. Major adverse CV events (MACE) included MI/CV death, hospitalization for heart failure or unstable angina, and late unplanned coronary artery bypass graft. The prognostic association and net reclassification improvement by ischemia for MI/CV death were determined.ResultsOut of 755 patients (age 64 ± 11 years, 64% male), we observed 97 MI/CV deaths and 210 MACE over a median follow-up of 5.3 years. Presence of ischemia demonstrated a significant association with MI/CV death (HR: 2.30; 95% CI: 1.54-3.44; P < 0.001) and MACE (HR: 2.24 ([95% CI: 1.69-2.95; P < 0.001). In a multivariate model adjusted for CV risk factors, ischemia maintained strong association with MI/CV death (HR: 1.84; 95% CI: 1.17-2.88; P = 0.008) and MACE (HR: 1.77; 95% CI: 1.31-2.40; P < 0.001) and reclassified 95% of patients at intermediate pretest risk (62% to low risk, 33% to high risk) with corresponding changes in the observed event rates of 1.4% and 5.3% per year for low and high post-test risk, respectively.ConclusionsIn a multicenter cohort of patients with known CAD, CMR-assessed ischemia was strongly associated with MI/CV death and reclassified patient risk beyond CV risk factors, especially in those considered to be at intermediate risk. Absence of ischemia was associated with a <2% annual rate of MI/CV death. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891)     

Comparative Outcomes After Percutaneous Coronary Intervention in Unconscious and Conscious Patients With Out-of-Hospital Cardiac Arrest

BackgroundUp to 70% of out-of-hospital cardiac arrest (OHCA) patients have a relevant coronary stenosis which may need revascularization. The short- and long-term ischemic and bleeding risk of unconscious and conscious OHCA patients undergoing percutaneous coronary intervention (PCI) is largely unknown.ObjectivesThis study sought to compare the occurrence of 1-year outcomes after PCI between OHCA patients, stratified on the basis of state of consciousness, with patients with acute coronary syndrome (ACS) not preceded by OHCA.MethodsThe study assessed the unadjusted and adjusted risk of cardiovascular events in a prospective single-center cohort of 9,303 consecutive PCI patients.ResultsAt 1 year, all-cause mortality was higher in unconscious (49.5%) but not in conscious OHCA (8.9%) patients than in ACS patients (8.0%), and both unconscious and conscious OHCA patients were more likely than ACS patients to experience definite stent thrombosis (4.4% and 3.5% vs 1.3%) and Bleeding Academic Research Consortium 3 or 5 bleeding (17.8% and 9.0% vs 5.1%). The higher hazards were largely determined by events occurring in the first 30 days. After multivariable adjustment, only unconscious OHCA patients remained at increased risk of death (adjusted HR: 3.27; 95% CI: 2.65-4.05), definite stent thrombosis (adjusted HR: 2.40; 95% CI: 1.30-4.43), and Bleeding Academic Research Consortium 3 or 5 bleeding (adjusted HR: 2.51; 95% CI: 1.82-3.47) at 1 year.ConclusionsAt 1 year after PCI, unconscious OHCA patients were at higher risk of death, definite stent thrombosis, and bleeding, while conscious OHCA patients had similar hazards compared with an all-comer ACS population without OHCA. Dedicated PCI strategies for OHCA patients taking into account their state of consciousness after resuscitation are warranted.     

Impact of Early Revascularization on Major Adverse Cardiovascular Events in Relation to Automatically Quantified Ischemia

ObjectivesUsing a contemporary, multicenter international single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) registry, this study characterized the potential major adverse cardiovascular event(s) (MACE) benefit of early revascularization based on automatic quantification of ischemia.BackgroundPrior single-center data reported an association between moderate to severe ischemia SPECT-MPI and reduced cardiac death with early revascularization.MethodsConsecutive patients from a multicenter, international registry who underwent ^99mTc SPECT-MPI between 2009 and 2014 with solid-state scanners were included. Ischemia was quantified automatically as ischemic total perfusion deficit (TPD). Early revascularization was defined as within 90 days. The primary outcome was MACE (death, myocardial infarction, and unstable angina). A propensity score was developed to adjust for nonrandomization of revascularization; then, multivariable Cox modeling adjusted for propensity score and demographics was used to predict MACE.ResultsIn total, 19,088 patients were included, with a mean follow-up of 4.7 ± 1.6 years, during which MACE occurred in 1,836 (9.6%) patients. There was a significant interaction between ischemic TPD modeled as a continuous variable and early revascularization (interaction p value: 0.012). In this model, there was a trend toward reduced MACE in patients with >5.4% ischemic TPD and a significant association with reduced MACE in patients with >10.2% ischemic TPD.ConclusionsIn this large, international, multicenter study reflecting contemporary cardiology practice, early revascularization of patients with >10.2% ischemia on SPECT-MPI, quantified automatically, was associated with reduced MACE.