Intravascular Imaging-Guided or Angiography-Guided Complex PCI.

BACKGROUND: Data regarding clinical outcomes after intravascular imaging-guided percutaneous coronary intervention (PCI) for complex coronary-artery lesions, as compared with outcomes after angiography-guided PCI, are limited. METHODS: In this prospective, multicenter, open-label trial in South Korea, we randomly assigned patients with complex coronary-artery lesions in a 2:1 ratio to undergo either intravascular imaging-guided PCI or angiography-guided PCI. In the intravascular imaging group, the choice between intravascular ultrasonography and optical coherence tomography was at the operators' discretion. The primary end point was a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization. Safety was also assessed. RESULTS: A total of 1639 patients underwent randomization, with 1092 assigned to undergo intravascular imaging-guided PCI and 547 assigned to undergo angiography-guided PCI. At a median follow-up of 2.1 years (interquartile range, 1.4 to 3.0), a primary end-point event had occurred in 76 patients (cumulative incidence, 7.7%) in the intravascular imaging group and in 60 patients (cumulative incidence, 12.3%) in the angiography group (hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.89; P = 0.008). Death from cardiac causes occurred in 16 patients (cumulative incidence, 1.7%) in the intravascular imaging group and in 17 patients (cumulative incidence, 3.8%) in the angiography group; target-vessel-related myocardial infarction occurred in 38 (cumulative incidence, 3.7%) and 30 (cumulative incidence, 5.6%), respectively; and clinically driven target-vessel revascularization in 32 (cumulative incidence, 3.4%) and 25 (cumulative incidence, 5.5%), respectively. There were no apparent between-group differences in the incidence of procedure-related safety events. CONCLUSIONS: Among patients with complex coronary-artery lesions, intravascular imaging-guided PCI led to a lower risk of a composite of death from cardiac causes, target-vessel-related myocardial infarction, or clinically driven target-vessel revascularization than angiography-guided PCI. (Supported by Abbott Vascular and Boston Scientific; RENOVATE-COMPLEX-PCI ClinicalTrials.gov number, NCT03381872).

Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial.

BACKGROUND: Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. METHODS: PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. FINDINGS: Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). INTERPRETATION: In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. FUNDING: The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.

Fractional Flow Reserve or Intravascular Ultrasonography to Guide PCI.

BACKGROUND: In patients with coronary artery disease who are being evaluated for percutaneous coronary intervention (PCI), procedures can be guided by fractional flow reserve (FFR) or intravascular ultrasonography (IVUS) for decision making regarding revascularization and stent implantation. However, the differences in clinical outcomes when only one method is used for both purposes are unclear. METHODS: We randomly assigned 1682 patients who were being evaluated for PCI for the treatment of intermediate stenosis (40 to 70% occlusion by visual estimation on coronary angiography) in a 1:1 ratio to undergo either an FFR-guided or IVUS-guided procedure. FFR or IVUS was to be used to determine whether to perform PCI and to assess PCI success. In the FFR group, PCI was to be performed if the FFR was 0.80 or less. In the IVUS group, the criteria for PCI were a minimal lumen area measuring either 3 mm2 or less or measuring 3 to 4 mm2 with a plaque burden of more than 70%. The primary outcome was a composite of death, myocardial infarction, or revascularization at 24 months after randomization. We tested the noninferiority of the FFR group as compared with the IVUS group (noninferiority margin, 2.5 percentage points). RESULTS: The frequency of PCI was 44.4% among patients in the FFR group and 65.3% among those in the IVUS group. At 24 months, a primary-outcome event had occurred in 8.1% of the patients in the FFR group and in 8.5% of those in the IVUS group (absolute difference, -0.4 percentage points; upper boundary of the one-sided 97.5% confidence interval, 2.2 percentage points; P = 0.01 for noninferiority). Patient-reported outcomes as reported on the Seattle Angina Questionnaire were similar in the two groups. CONCLUSIONS: In patients with intermediate stenosis who were being evaluated for PCI, FFR guidance was noninferior to IVUS guidance with respect to the composite primary outcome of death, myocardial infarction, or revascularization at 24 months. (Funded by Boston Scientific; FLAVOUR ClinicalTrials.gov number, NCT02673424.).

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Fractional flow reserve versus angiography-guided strategy in acute myocardial infarction with multivessel disease: a randomized trial.

AIMS: In patients with acute myocardial infarction (MI) and multivessel coronary artery disease, percutaneous coronary intervention (PCI) of non-infarct-related artery reduces death or MI. However, whether selective PCI guided by fractional flow reserve (FFR) is superior to routine PCI guided by angiography alone is unclear. The current trial sought to compare FFR-guided PCI with angiography-guided PCI for non-infarct-related artery lesions among patients with acute MI and multivessel disease. METHODS AND RESULTS: Patients with acute MI and multivessel coronary artery disease who had undergone successful PCI of the infarct-related artery were randomly assigned to either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis of >50%) for non-infarct-related artery lesions. The primary end point was a composite of time to death, MI, or repeat revascularization. A total of 562 patients underwent randomization. Among them, 60.0% underwent immediate PCI for non-infarct-related artery lesions and 40.0% were treated by a staged procedure during the same hospitalization. PCI was performed for non-infarct-related artery in 64.1% in the FFR-guided PCI group and 97.1% in the angiography-guided PCI group, and resulted in significantly fewer stent used in the FFR-guided PCI group (2.2 ± 1.1 vs. 2.5 ± 0.9, P < 0.001). At a median follow-up of 3.5 years (interquartile range: 2.7-4.1 years), the primary end point occurred in 18 patients of 284 patients in the FFR-guided PCI group and in 40 of 278 patients in the angiography-guided PCI group (7.4% vs. 19.7%; hazard ratio, 0.43; 95% confidence interval, 0.25-0.75; P = 0.003). The death occurred in five patients (2.1%) in the FFR-guided PCI group and in 16 patients (8.5%) in the angiography-guided PCI group; MI in seven (2.5%) and 21 (8.9%), respectively; and unplanned revascularization in 10 (4.3%) and 16 (9.0%), respectively. CONCLUSION: In patients with acute MI and multivessel coronary artery disease, a strategy of selective PCI using FFR-guided decision-making was superior to a strategy of routine PCI based on angiographic diameter stenosis for treatment of non-infarct-related artery lesions regarding the risk of death, MI, or repeat revascularization.

Microvascular resistance reserve: diagnostic and prognostic performance in the ILIAS registry.

AIMS: The microvascular resistance reserve (MRR) was introduced as a means to characterize the vasodilator reserve capacity of the coronary microcirculation while accounting for the influence of concomitant epicardial disease and the impact of administration of potent vasodilators on aortic pressure. This study aimed to evaluate the diagnostic and prognostic performance of MRR. METHODS AND RESULTS: A total of 1481 patients with stable symptoms and a clinical indication for coronary angiography were included from the global ILIAS Registry. MRR was derived as a function of the coronary flow reserve (CFR) divided by the fractional flow reserve (FFR) and corrected for driving pressure. The median MRR was 2.97 [Q1-Q3: 2.32-3.86] and the overall relationship between MRR and CFR was good [correlation coefficient (Rs) = 0.88, P < 0.005]. The difference between CFR and MRR increased with decreasing FFR [coefficient of determination (R2) = 0.34; Coef.-2.88, 95% confidence interval (CI): -3.05--2.73; P < 0.005]. MRR was independently associated with major adverse cardiac events (MACE) at 5-year follow-up [hazard ratio (HR) 0.78; 95% CI 0.63-0.95; P = 0.024] and with target vessel failure (TVF) at 5-year follow-up (HR 0.83; 95% CI 0.76-0.97; P = 0.047). The optimal cut-off value of MRR was 3.0. Based on this cut-off value, only abnormal MRR was significantly associated with MACE and TVF at 5-year follow-up in vessels with functionally significant epicardial disease (FFR <0.75). CONCLUSION: MRR seems a robust indicator of the microvascular vasodilator reserve capacity. Moreover, in line with its theoretical background, this study suggests a diagnostic advantage of MRR over other indices of vasodilatory capacity in patients with hemodynamically significant epicardial coronary artery disease.

Preventive PCI or medical therapy alone for vulnerable atherosclerotic coronary plaque: Rationale and design of the randomized, controlled PREVENT trial.

BACKGROUND: Acute coronary syndromes are commonly caused by the rupture of vulnerable plaque, which often appear angiographically not severe. Although pharmacologic management is considered standard therapy for stabilizing plaque vulnerability, the potential role of preventive local treatment for vulnerable plaque has not yet been determined. The PREVENT trial was designed to compare preventive percutaneous coronary intervention (PCI) plus optimal medical therapy (OMT) with OMT alone in patients with functionally nonsignificant high-risk vulnerable plaques. METHODS: The PREVENT trial is a multinational, multicenter, prospective, open-label, active-treatment-controlled randomized trial. Eligible patients have at least 1 angiographically significant stenosis (diameter stenosis >50% by visual estimation) without functional significance (fractional flow reserve [FFR] >0.80). Target lesions are assessed by intracoronary imaging and must meet at least 2 imaging criteria for vulnerable plaque; (1) minimal lumen area <4.0 mm2; (2) plaque burden >70%; (3) maximal lipid core burden index in a 4 mm segment >315 by near infrared spectroscopy; and (4) thin cap fibroatheroma as determined by virtual histology or optical coherence tomography. Enrolled patients are randomly assigned in a 1:1 ratio to either preventive PCI with either bioabsorbable vascular scaffolds or metallic everolimus-eluting stents plus OMT or OMT alone. The primary endpoint is target-vessel failure, defined as the composite of death from cardiac causes, target-vessel myocardial infarction, ischemic-driven target-vessel revascularization, or hospitalization for unstable or progressive angina, at 2 years after randomization. RESULTS: Enrollment of a total of 1,608 patients has been completed. Follow-up of the last enrolled patient will be completed in September 2023 and primary results are expected to be available in early 2024. CONCLUSIONS: The PREVENT trial is the first large-scale, randomized trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaques containing multiple high-risk features that is appropriately powered for clinical outcomes. PREVENT will provide compelling evidence as to whether preventive PCI of vulnerable plaques plus OMT improves patient outcomes compared with OMT alone. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT02316886. KEY POINTS: The PREVENT trial is the first, large-scale randomized clinical trial to evaluate the effect of preventive PCI on non-flow-limiting vulnerable plaque with high-risk features. It will provide compelling evidence to determine whether PCI of focal vulnerable plaques on top of OMT improves patient outcomes.

Impact of diabetes on long-term outcomes of bifurcation percutaneous coronary intervention. An analysis from the BIFURCAT registry.

BACKGROUND: It is still unclear the impact of diabetes mellitus (DM) in complex coronary lesions treated with percutaneous coronary intervention (PCI) which themselves are at increased incidence of adverse events. METHODS: BIFURCAT registry encompassed patients treated with PCI for coronary bifurcation lesion from the COBIS III and the RAIN registry. The primary endpoint was the occurrence of major cardiovascular adverse event (MACE), a composite and mutual exclusive of all-cause death or myocardial infarction (MI) or target-lesion revascularization (TLR). A total of 5537 patients were included in the analysis and 1834 (33%) suffered from DM. RESULTS: After a median follow-up of 21 months, diabetic patients had a higher incidence of MACE (17% vs. 9%, p < 0.001), all-cause mortality (9% vs. 4%, p < 0.001), TLR (5% vs. 3%, p = 0.001), MI (4% vs. 2%, p < 0.001), and stent thrombosis (ST) (2% vs. 1%, p = 0.007). After multivariate analysis, diabetes remained significantly associated with MACE (hazard ratio [HR]: 1.37; confidence interval [CI]: 1.13-1.65; p = 0.001), all-cause death (HR: 1.65; 95% CI: 1.24-2.19, p = 0.001), TLR (HR: 1.45; CI: 1.03-2.04; p = 0.031) and ST (HR: 1.73, CI: 1.04-2.88; p = 0.036), but not with MI (HR: 1.34; CI: 0.93-1.92; p = 0.11). Among diabetics, chronic kidney disease (HR: 2.99; CI: 2.21-4.04), baseline left ventricular ejection fraction (HR: 0.98; CI: 0.97-0.99), femoral access (HR: 1.62; CI: 1.23-2.15), left main coronary artery (HR: 1.44; CI: 1.06-1.94), main branch diameter (HR: 0.79; CI: 0.66-0.94) and final kissing balloon (HR: 0.70; CI: 0.52-0.93) were independent predictors of MACE at follow-up. CONCLUSIONS: Patients with DM treated with PCI for coronary bifurcations have a worse prognosis due to higher incidence of MACE, all-cause mortality, TLR and ST compared to the non-diabetics.

Performance of a Novel CT-Derived Fractional Flow Reserve Measurement to Detect Hemodynamically Significant Coronary Stenosis.

BACKGROUND: Fractional flow reserve (FFR) based on computed tomography (CT) has been shown to better identify ischemia-causing coronary stenosis. However, this current technology requires high computational power, which inhibits its widespread implementation in clinical practice. This prospective, multicenter study aimed at validating the diagnostic performance of a novel simple CT based fractional flow reserve (CT-FFR) calculation method in patients with coronary artery disease. METHODS: Patients who underwent coronary CT angiography (CCTA) within 90 days and invasive coronary angiography (ICA) were prospectively enrolled. A hemodynamically significant lesion was defined as an FFR ≤ 0.80, and the area under the receiver operating characteristic curve (AUC) was the primary measure. After the planned analysis for the initial algorithm A, we performed another set of exploratory analyses for an improved algorithm B. RESULTS: Of 184 patients who agreed to participate in the study, 151 were finally analyzed. Hemodynamically significant lesions were observed in 79 patients (52.3%). The AUC was 0.71 (95% confidence interval [CI], 0.63-0.80) for CCTA, 0.65 (95% CI, 0.56-0.74) for CT-FFR algorithm A (P = 0.866), and 0.78 (95% CI, 0.70-0.86) for algorithm B (P = 0.112). Diagnostic accuracy was 0.63 (0.55-0.71) for CCTA alone, 0.66 (0.58-0.74) for algorithm A, and 0.76 (0.68-0.82) for algorithm B. CONCLUSION: This study suggests the feasibility of automated CT-FFR, which can be performed on-site within several hours. However, the diagnostic performance of the current algorithm does not meet the a priori criteria for superiority. Future research is required to improve the accuracy.

Relationship of Plaque Features at Coronary CT to Coronary Hemodynamics and Cardiovascular Events.

Background Plaque assessments with coronary CT angiography (CCTA) and coronary flow indexes have prognostic implications. Purpose To investigate the association and additive prognostic value of plaque burden and characteristics at CCTA with coronary pressure and flow. Materials and Methods Data of patients with coronary artery disease who underwent CCTA within 90 days before physiologic assessments at tertiary cardiovascular centers between January 2011 and December 2018 were retrospectively analyzed, which included fractional flow reserve (FFR), resting distal coronary artery pressure (Pd)-to-aortic pressure (Pa) ratio (hereafter, Pd/Pa), coronary flow reserve (CFR), hyperemic flow (1/hyperemic mean transit time [Tmn]), resting flow (1/resting Tmn), and index of microcirculatory resistance (IMR). Four high-risk plaque (HRP) attributes at CCTA defined high disease burden (plaque burden, ≥70%; minimum lumen area, <4 mm2) and adverse plaque (low-attenuation plaque, positive remodeling). Their lesion-specific relationships with coronary hemodynamic parameters and major adverse cardiovascular events (MACE) were investigated using a generalized estimating equation and marginal Cox model. Results Among 406 lesions from 335 patients (mean age, 67 years ± 10 [SD]; 259 men), high disease burden is predicted by FFR (odds ratio [OR], 0.55; P < .001), resting Pd/Pa (OR, 0.47; P < .001), CFR (OR, 0.85; P = .004), and hyperemic flow (OR, 0.91; P = .03), and adverse plaque by FFR (OR, 0.67; P < .001), resting Pd/Pa (OR, 0.69; P = .001), hyperemic flow (OR, 0.76; P = .006), resting flow (OR, 0.54; P = .001), and IMR (OR, 1.27; P = .008). High disease burden (hazard ratio [HR], 4.0; P = .004) and adverse plaque (HR, 2.7; P = .02) were associated with a higher risk of MACE (n = 27) over median 2.9-year follow-up. In six lesion subsets with normal flow or pressure, at least three HRP attributes predicted a higher MACE rate (HR range, 2.6-6.3). Conclusion High-risk plaque features and plaque burden at coronary CT angiography were associated with cardiovascular events independent of coronary hemodynamic parameters. Clinical trial registration no. NCT04037163 © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Leipsic and Tzimas in this issue.

Association between patient age, microcirculation, and coronary stenosis assessment with fractional flow reserve and instantaneous wave-free ratio.

OBJECTIVES: To investigate the effect of aging on coronary stenosis functional assessment with fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). BACKGROUND: Limited data exist regarding the impact of patient age on these coronary pressure indices. METHODS: We analyzed 514 patients with coronary stenosis interrogated with intravascular physiology. The influence of patient age on FFR, iFR, and microcirculation-related indices was investigated. Vessel-oriented composite outcome (VOCO) was assessed in the FFR-based deferred population according to iFR, coronary flow reserve (CFR), and age. RESULTS: FFR increased (r = 0.128, p = 0.004), iFR remained unchanged (r = -0.001, p = 0.980), and CFR decreased (r = -0.095, p = 0.001) with patient age. Relationship between FFR and CFR differed across age groups (r = 0.263 in <60 years old vs. r = 0.124 in ≥60 years old, p = 0.0056), whereas iFR correlated to CFR similarly regardless age (r = 0.283 in <60 years old vs. r = 0.219 in ≥60 years old, p = 0.3781). No differences were found on angiographic stenosis severity (%DS 47.4 in <60 years old and 49.8 in ≥60 years old, p = 0.317). At 5 years, FFR-based revascularisation deferral in patients ≥60 years old was associated with more VOCO when either iFR (25%) or CFR (16.9%) were abnormal, compared to patients with normal iFR (6.3%) or normal CFR (4.6%) (log-rank p < 0.001). This difference in clinical outcomes was not observed in younger patients. CONCLUSIONS: FFR values increased progressively with patient age, potentially associated with age-related changes in the coronary microcirculation. Conversely, iFR values remained unchanged across the patient age spectrum. In ≥60 years old patients with revascularisation deferral based on FFR, both abnormal iFR and CFR values were associated with worse long-term patient outcomes.

Age-related changes in the coronary microcirculation influencing the diagnostic performance of invasive pressure-based indices and long-term patient prognosis.

OBJECTIVES: Investigate age-related changes in coronary microvascular function, its effect on hyperemic and non-hyperemic indices of stenosis relevance, and its prognostic implications. BACKGROUND: Evidence assessing the effect of age on fractional flow reserve (FFR), resting mean distal intracoronary pressure/mean aortic pressure (Pd/Pa), and microcirculatory function remains scarce. METHODS: This is a post hoc study of a large prospective international registry (NCT03690713) including 1134 patients (1326 vessels) with coronary stenoses interrogated with pressure and flow guidewires. Age-dependent correlations with functional indices were analyzed. Prevalences of FFR, resting Pd/Pa, and coronary flow reserve (CFR) classification agreement were assessed. At 5 years follow-up, the relation between resting Pd/Pa, CFR, and their age-dependent implications on FFR-guided percutaneous coronary intervention (PCI) deferral (deferred if FFR > 0.80) were investigated using vessel-oriented composite outcomes (VOCO) composed of death, myocardial infarction, and repeated revascularization. RESULTS: Age correlated positively with FFR (r = 0.08, 95% confidence interval [CI]: 0.03 to 0.13, p = 0.005), but not with resting Pd/Pa (r = -0.03, 95% CI:-0.09 to 0.02, p = 0.242). CFR correlated negatively with age (r = -0.15, 95% CI: -0.21 to -0.10, p < 0.001) due to a significant decrease in maximal hyperemic flow in older patients. Patients over 60 years of age with FFR-guided deferred-PCI abnormal resting Pd/Pa or abnormal CFR had increased risk of VOCO (hazard ratio [HR]: 2.10, 95% CI: 1.15 to 4.36, p = 0.048; HR: 2.46, 95% CI:1.23 to 4.96, p = 0.011; respectively). CONLUSIONS: Aging is associated with decrease in microcirculatory vasodilation, as assessed with adenosine-based methods like CFR. In patients older than 60 years in whom PCI is deferred according to FFR > 0.80, CFR and resting Pd/Pa have an incremental value in predicting future vessel-oriented patient outcomes.

Prediction of functional results of percutaneous coronary interventions with virtual stenting and quantitative flow ratio.

BACKGROUND: The clinical value of residual quantitative flow ratio (rQFR), a novel function of QFR technique, is unknown. AIM: We investigated the clinical value of rQFR, aimed to predict residual ischemia after virtual percutaneous coronary intervention (vPCI). METHODS: This is a substudy of the COE-PERSPECTIVE registry, which investigated the prognostic value of post-PCI fractional flow reserve (FFR). From pre-PCI angiograms, QFR and rQFR were analyzed and their diagnostic performance was assessed at blinded fashion using pre-PCI FFR and post-PCI FFR as reference, respectively. The prognostic value of rQFR after vPCI was assessed according to vessel-oriented composite outcome (VOCO) at 2 years. RESULTS: We analyzed 274 patients (274 vessels) with FFR-based ischemic causing lesions (49%) from 555 screened patients. Pre-PCI QFR and FFR were 0.63 ± 0.10 and 0.66 ± 0.11 (R = 0.756, p < 0.001). rQFR after vPCI and FFR after real PCI were 0.93 ± 0.06 and 0.86 ± 0.07 (R = 0.528, p < 0.001). The mean difference between rQFR and post-PCI FFR was 0.068 (95% limit of agreement: -0.05 to 0.19). Diagnostic performance of rQFR to predict residual ischemia after PCI was good (area under the curve [AUC]: 0.856 [0.804-0.909], p < 0.001). rQFR predicted well the incidence of 2-year VOCO after index PCI (AUC: 0.712 [0.555-0.869], p = 0.041), being similar to that of actual post-PCI FFR (AUC: 0.691 [0.512-0.870], p = 0.061). rQFR ≤0.89 was associated with increased risk of 2-year VOCO (hazard ratio [HR]: 12.9 [2.32-71.3], p = 0.0035). This difference was mainly driven by a higher rate of target vessel revascularization (HR: 16.98 [2.33-123.29], p = 0.0051). CONCLUSIONS: rQFR estimated from pre-PCI angiography and virtual coronary stenting mildly overestimated functional benefit of PCI. However, it well predicted suboptimal functional result and long-term vessel-related clinical events. CLINICAL TRIAL REGISTRATION: Influence of fractional flow reserve on the Clinical OutcomEs of PERcutaneouS Coronary Intervention (COE-PESPECTIVE) Registry, NCT01873560.

Coronary CTA With AI-QCT Interpretation: Comparison With Myocardial Perfusion Imaging for Detection of Obstructive Stenosis Using Invasive Angiography as Reference Standard.

BACKGROUND. Deep learning frameworks have been applied to interpretation of coronary CTA performed for coronary artery disease (CAD) evaluation. OBJECTIVE. The purpose of our study was to compare the diagnostic performance of myocardial perfusion imaging (MPI) and coronary CTA with artificial intelligence quantitative CT (AI-QCT) interpretation for detection of obstructive CAD on invasive angiography and to assess the downstream impact of including coronary CTA with AI-QCT in diagnostic algorithms. METHODS. This study entailed a retrospective post hoc analysis of the derivation cohort of the prospective 23-center Computed Tomographic Evaluation of Atherosclerotic Determinants of Myocardial Ischemia (CREDENCE) trial. The study included 301 patients (88 women and 213 men; mean age, 64.4 ± 10.2 [SD] years) recruited from May 2014 to May 2017 with stable symptoms of myocardial ischemia referred for nonemergent invasive angiography. Patients underwent coronary CTA and MPI before angiography with quantitative coronary angiography (QCA) measurements and fractional flow reserve (FFR). CTA examinations were analyzed using an FDA-cleared cloud-based software platform that performs AI-QCT for stenosis determination. Diagnostic performance was evaluated. Diagnostic algorithms were compared. RESULTS. Among 102 patients with no ischemia on MPI, AI-QCT identified obstructive (≥ 50%) stenosis in 54% of patients, including severe (≥ 70%) stenosis in 20%. Among 199 patients with ischemia on MPI, AI-QCT identified nonobstructive (1-49%) stenosis in 23%. AI-QCT had significantly higher AUC (all p < .001) than MPI for predicting ≥ 50% stenosis by QCA (0.88 vs 0.66), ≥ 70% stenosis by QCA (0.92 vs 0.81), and FFR < 0.80 (0.90 vs 0.71). An AI-QCT result of ≥ 50% stenosis and ischemia on stress MPI had sensitivity of 95% versus 74% and specificity of 63% versus 43% for detecting ≥ 50% stenosis by QCA measurement. Compared with performing MPI in all patients and those showing ischemia undergoing invasive angiography, a scenario of performing coronary CTA with AIQCT in all patients and those showing ≥ 70% stenosis undergoing invasive angiography would reduce invasive angiography utilization by 39%; a scenario of performing MPI in all patients and those showing ischemia undergoing coronary CTA with AI-QCT and those with ≥ 70% stenosis on AI-QCT undergoing invasive angiography would reduce invasive angiography utilization by 49%. CONCLUSION. Coronary CTA with AI-QCT had higher diagnostic performance than MPI for detecting obstructive CAD. CLINICAL IMPACT. A diagnostic algorithm incorporating AI-QCT could substantially reduce unnecessary downstream invasive testing and costs. TRIAL REGISTRATION. Clinicaltrials.gov NCT02173275.

Long-Term Clinical Outcomes and Its Predictors Between the 1- and 2-Stent Strategy in Coronary Bifurcation Lesions　- A Baseline Clinical and Lesion Characteristic-Matched Analysis.

BACKGROUND: Differences in the impact of the 1- or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions.Methods and Results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (pinteraction=0.008) and side branch calcification (pinteraction=0.010). CONCLUSIONS: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.

Impact of stent designs of second-generation drug-eluting stents on long-term outcomes in coronary bifurcation lesions.

OBJECTIVES: We compared the long-term clinical outcomes of four different types of second-generation drug-eluting stents (DESs) in coronary bifurcation lesions. BACKGROUND: Clinical outcomes of different designs of second-generation DESs are not well known in bifurcation lesions. METHODS: Patients who underwent percutaneous coronary intervention with second-generation DESs for coronary bifurcation lesion were enrolled from 21 centers in South Korea. A total of 2,526 patients was evaluated and divided into four treatment groups according to DES type: bioabsorbable polymer biolimus-eluting stent (BP-BES group, n = 514), platinum chromium everolimus-eluting stent (PtCr-EES group, n = 473), cobalt nickel zotarolimus-eluting stent (CoNi-ZES group, n = 736), or cobalt chromium everolimus-eluting stent (CoCr-EES group, n = 803). Primary outcome was target lesion failure (TLF, defined as a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularization). Inverse probability of treatment weighting (IPTW) was performed to reduce selection bias and potential confounding factors. RESULTS: For 5 years of follow-up, the rates of TLF among the four DES groups were not significantly different (6.2% for BP-BES group, 8.2% for PtCr-EES group, 6.5% for CoNi-ZES group, and 8.6% for CoCr-EES group, p = .434). The results were consistent after IPTW adjustment (6.8, 8.4, 6.0, and 7.5%, respectively, p = .554). In subgroup analysis, the similarity of long-term outcomes among the four different types of second-generation DES was consistent across subgroups regardless of side branch treatment (p for interaction = .691). CONCLUSION: There seems to be no significant difference in long-term clinical outcomes among patients who received different types of second-generation DES for coronary bifurcation lesion.

Residual functional SYNTAX score by quantitative flow ratio and improvement of exercise capacity after revascularization.

OBJECTIVES: This study aimed to evaluate the association between improvement in exercise capacity and functional completeness of revascularization, determined by residual functional SYNTAX score (rFSS), which is the sum of residual SYNTAX score of the vessels with post- percutaneous coronary intervention (PCI) quantitative flow ratio (QFR) ≤0.80. BACKGROUND: In patients with stable ischemic heart disease (SIHD), the efficacy of PCI in improving exercise capacity has been under debate and the differential effect of PCI for exercise capacity, according to functional completeness of revascularization, has not been evaluated. METHODS: Among patients enrolled in the QFR multicenter registry, 110 patients who underwent routine exercise treadmill tests before and after PCI were analyzed. Patients were classified into functional complete revascularization (CR) group (rFSS = 0) and functional incomplete revascularization (IR) group (rFSS ≥ 1). Increase of exercise time after PCI was compared between the two groups. Improvement of exercise capacity was defined as ≥10% increase of exercise time after PCI. RESULTS: Functional CR was achieved in 79 patients (71.8%), otherwise classified as functional IR in 31 patients (28.2%) without differences in baseline characteristics including medication profiles. Increase of exercise time was significantly associated with increase of 3-vessel QFR (sum of QFRs in all three vessels; r = .198, p = .038) and rFSS (r = -.312, p < .001), but not with decrease of SYNTAX score (r = .097, p = .313). The rFSS showed significantly higher c-index to predict the improvement of exercise capacity after PCI than increase of 3-vessel QFR or decrease of SYNTAX score (0.722 vs. 0.627 vs. 0.492, respectively, p < 0.001). Patients with functional CR, defined by rFSS, showed significantly higher absolute and relative increase in exercise time than those with functional IR (97.7 s vs. 12.5 s, p < .001; 25.4% vs. 3.6%, p = .001). Functional CR was an independent predictor for improvement of exercise capacity after PCI (adjusted OR 4.656, 95% CI 1.678-12.920, p = .002). CONCLUSIONS: Integrated anatomic and functional scoring system (rFSS) was significantly associated with improvement of exercise capacity after PCI. SIHD patients with functional CR, defined by rFSS, showed significantly higher exercise capacity after PCI than those with functional IR.

Characteristic findings of microvascular dysfunction on coronary computed tomography angiography in patients with intermediate coronary stenosis.

OBJECTIVES: We aimed to assess the prevalence of coexistence of coronary microvascular dysfunction (CMD) in patients with intermediate epicardial stenosis and to explore coronary computed tomography angiography (CCTA)-derived lesion-, vessel-, and cardiac fat-related characteristic findings associated with CMD. METHODS: A retrospective cross-sectional single-center study included a total of 177 patients with intermediate stenosis in the left anterior descending artery (LAD) who underwent CCTA and invasive physiological measurements. The 320-slice CCTA analysis included qualitative and quantitative assessments of plaque, vessel, epicardial fat volume (ECFV) and epicardial fat attenuation (ECFA), and pericoronary fat attenuation (FAI). CMD was defined by the index of microcirculatory resistance (IMR) ≥ 25. RESULTS: In the entire cohort, median fractional flow reserve (FFR) and median IMR values were 0.77 (0.69-0.84) and 19.0 (13.7-27.7), respectively. The prevalence of CMD was 32.8 % (58/177) in the total cohort. The coexistence of CMD and functionally significant stenosis was 34.3 % (37/108), whereas CMD in nonsignificant intermediate stenosis was 30.4 % (21/69). CMD was significantly associated with greater lumen volume (p = 0.031), greater fibrofatty and necrotic component (FFNC) volume (p = 0.030), and greater ECFV (p = 0.030), but not with FAI (p = 0.832) and ECFA (p = 0.445). On multivariable logistic regression analysis, vessel volume, vessel lumen volume, lesion remodeling index, ECFV, and lesion FFNC volume were independent predictors of CMD. CONCLUSIONS: The prevalence of CMD was about one-third in patients with intermediate stenosis in LAD regardless of the presence or absence of functional stenosis significance. The integrated CCTA assessment may help in the identification of CMD. KEY POINTS: • The coexistence of coronary microvascular dysfunction (CMD) and functionally significant stenosis was 34.3 %, whereas CMD in nonsignificant intermediate stenosis was 30.4 %. • Coronary computed tomography angiography (CCTA)-derived CMD characteristics were vessel volume, vessel lumen volume, remodeling index, epicardial fat volume, and fibrofatty necrotic core volume. • Integrated CCTA assessment may help identify the coexistence of CMD and epicardial stenosis.

Comparison of 2-Stenting Strategies Depending on Sequence or Technique for Bifurcation Lesions in the Second-Generation Drug-Eluting Stent Era　- Analysis From the COBIS (Coronary Bifurcation Stenting) III Registry.

BACKGROUND: It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years' TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis. CONCLUSIONS: The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.

Impact of Cardiovascular Risk Factors and Cardiovascular Diseases on Outcomes in Patients Hospitalized with COVID-19 in Daegu Metropolitan City.

BACKGROUND: Data regarding the association between preexisting cardiovascular risk factors (CVRFs) and cardiovascular diseases (CVDs) and the outcomes of patients requiring hospitalization for coronavirus disease 2019 (COVID-19) are limited. Therefore, the aim of this study was to investigate the impact of preexisting CVRFs or CVDs on the outcomes of patients with COVID-19 hospitalized in a Korean healthcare system. METHODS: Patients with COVID-19 admitted to 10 hospitals in Daegu Metropolitan City, Korea, were examined. All sequentially hospitalized patients between February 15, 2020, and April 24, 2020, were enrolled in this study. All patients were confirmed to have COVID-19 based on the positive results on the polymerase chain reaction testing of nasopharyngeal samples. Clinical outcomes during hospitalization, such as requiring intensive care and invasive mechanical ventilation (MV) and death, were evaluated. Moreover, data on baseline comorbidities such as a history of diabetes, hypertension, dyslipidemia, current smoking, heart failure, coronary artery disease, cerebrovascular accidents, and other chronic cardiac diseases were obtained. RESULTS: Of all the patients enrolled, 954 (42.0%) had preexisting CVRFs or CVDs. Among the CVRFs, the most common were hypertension (28.8%) and diabetes mellitus (17.0%). The prevalence rates of preexisting CVRFs or CVDs increased with age (P < 0.001). The number of patients requiring intensive care (P < 0.001) and invasive MV (P < 0.001) increased with age. The in-hospital death rate increased with age (P < 0.001). Patients requiring intensive care (5.3% vs. 1.6%; P < 0.001) and invasive MV (4.3% vs. 1.7%; P < 0.001) were significantly greater in patients with preexisting CVRFs or CVDs. In-hospital mortality (12.9% vs. 3.1%; P < 0.001) was significantly higher in patients with preexisting CVRFs or CVDs. Among the CVRFs, diabetes mellitus and hypertension were associated with increased requirement of intensive care and invasive MV and in-hospital death. Among the known CVDs, coronary artery disease and congestive heart failure were associated with invasive MV and in-hospital death. In multivariate analysis, preexisting CVRFs or CVDs (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.07-3.01; P = 0.027) were independent predictors of in-hospital death after adjusting for confounding variables. Among individual preexisting CVRF or CVD components, diabetes mellitus (OR, 2.43; 95% CI, 1.51-3.90; P < 0.001) and congestive heart failure (OR, 2.43; 95% CI, 1.06-5.87; P = 0.049) were independent predictors of in-hospital death. CONCLUSION: Based on the findings of this study, the patients with confirmed COVID-19 with preexisting CVRFs or CVDs had worse clinical outcomes. Caution is required in dealing with these patients at triage.