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.).

Aspirin Versus Clopidogrel for Long-Term Maintenance Monotherapy After Percutaneous Coronary Intervention: The HOST-EXAM Extended Study.

BACKGROUND: Long-term outcomes of antiplatelet monotherapy in patients who receive percutaneous coronary intervention are unknown. The HOST-EXAM (Harmonizing Optimal Strategy for Treatment of Coronary Artery Stenosis-Extended Antiplatelet Monotherapy) Extended study reports the posttrial follow-up results of the original HOST-EXAM trial. METHODS: From March 2014 through May 2018, 5438 patients who maintained dual antiplatelet therapy without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents were randomly assigned in a 1:1 ratio to receive clopidogrel (75 mg once daily) or aspirin (100 mg once daily). The primary end point (a composite of all-cause death, nonfatal myocardial infarction, stroke, readmission attributable to acute coronary syndrome, and Bleeding Academic Research Consortium type 3 or greater bleeding), secondary thrombotic end point (cardiac death, nonfatal myocardial infarction, ischemic stroke, readmission attributable to acute coronary syndrome, and definite or probable stent thrombosis), and bleeding end point (Bleeding Academic Research Consortium type 2 or greater bleeding) were analyzed during the extended follow-up period. Analysis was performed on the per-protocol population (2431 patients in the clopidogrel group and 2286 patients in the aspirin group). RESULTS: During a median follow-up of 5.8 years (interquartile range, 4.8-6.2 years), the primary end point occurred in 12.8% and 16.9% in the clopidogrel and aspirin groups, respectively (hazard ratio, 0.74 [95% CI, 0.63-0.86]; P<0.001). The clopidogrel group had a lower risk for the secondary thrombotic end point (7.9% versus 11.9%; hazard ratio, 0.66 [95% CI, 0.55-0.79]; P<0.001) and secondary bleeding end point (4.5% versus 6.1%; hazard ratio, 0.74 [95% CI, 0.57-0.94]; P=0.016). There was no significant difference in the incidence of all-cause death between the 2 groups (6.2% versus 6.0%; hazard ratio, 1.04 [95% CI, 0.82-1.31]; P=0.742). Landmark analysis at 2 years showed that the beneficial effect of clopidogrel was consistent throughout the follow-up period. CONCLUSIONS: During an extended follow-up of >5 years after randomization, clopidogrel monotherapy compared with aspirin monotherapy was associated with lower rates of the composite net clinical outcome in patients without clinical events for 12±6 months after percutaneous coronary intervention with drug-eluting stents. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02044250.

Comparison of 3- to 6-Month Versus 12-Month Dual Antiplatelet Therapy After Coronary Intervention Using the Contemporary Drug-Eluting Stents With Ultrathin Struts: The HOST-IDEA Randomized Clinical Trial.

BACKGROUND: Limited data are available on short-term dual antiplatelet therapy (DAPT) after percutaneous coronary intervention using third-generation drug-eluting stents with ultrathin struts and advanced polymer technology. We investigated whether 3- to 6-month DAPT was noninferior to 12-month DAPT after implantation of drug-eluting stents with ultrathin struts and advanced polymer technology. METHODS: We performed an open-label, randomized trial at 37 centers in South Korea. We enrolled patients undergoing percutaneous coronary intervention using the Orsiro biodegradable-polymer sirolimus-eluting stents or the Coroflex ISAR polymer-free sirolimus-eluting stents. Patients with ST-segment-elevation myocardial infarction were excluded. Patients were randomly assigned to receive either 3- to 6-month or 12-month DAPT after percutaneous coronary intervention. The choice of antiplatelet medications was at the physician's discretion. The primary outcome was a net adverse clinical event, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, stent thrombosis, or major bleeding, defined as Bleeding Academic Research Consortium type 3 or 5 at 12 months. The major secondary outcomes were target lesion failure, a composite of cardiac death, target vessel myocardial infarction, clinically driven target lesion revascularization, and major bleeding. RESULTS: A total of 2013 patients (mean age, 65.7±10.5 years; 1487 males [73.9%]; 1110 [55.1%] presented with acute coronary syndrome) were randomly assigned to 3- to 6-month DAPT (n=1002) or 12-month DAPT (n=1011). The primary outcome occurred in 37 (3.7%) patients in the 3- to 6-month DAPT group and 41 (4.1%) in the 12-month DAPT group. The noninferiority of the 3- to 6-month DAPT group to the 12-month DAPT group was met (absolute risk difference, -0.4% [1-sided 95% CI, -∞% to 1.1%]; P<0.001 for noninferiority). There were no significant differences in target lesion failure (hazard ratio, 0.98 [95% CI, 0.56-1.71], P=0.94) or major bleeding (hazard ratio, 0.82 [95% CI, 0.41-1.61], P=0.56) between the 2 groups. Across various subgroups, the treatment effect of 3- to 6-month DAPT was consistent for net adverse clinical event. CONCLUSIONS: Among patients undergoing percutaneous coronary intervention using third-generation drug-eluting stents, 3- to 6-month DAPT was noninferior to 12-month DAPT for net adverse clinical event. Further research is needed to generalize this finding to other populations and to determine the ideal regimen for 3- to 6-month DAPT. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02601157.

Genetic characterization of a locus responsible for low pungency using EMS-induced mutants in Capsicum annuum L.

KEY MESSAGE: The pepper mutants ('221-2-1a' and '1559-1-2h') with very low pungency were genetically characterized. The Pun4 locus, responsible for the reduced pungency of the mutant fruits, was localized to a 208 Mb region on chromosome 6. DEMF06G16460, encoding 3-ketoacyl-CoA synthase, was proposed as a strong candidate gene based on the genetic analyses of bulked segregants, DEG, and expression analyses. Capsaicinoids are unique alkaloids present in pepper (Capsicum spp.), synthesized through the condensation of by-products from the phenylpropanoid and branched-chain fatty acid pathways, and accumulating in the placenta. In this study, we characterized two allelic ethyl methanesulfonate-induced mutant lines with extremely low pungency ('221-2-1a' and '1559-1-2h'). These mutants, derived from the pungent Korean landrace 'Yuwolcho,' exhibited lower capsaicinoid content than Yuwolcho but still contained a small amount of capsaicinoid with functional capsaicinoid biosynthetic genes. Genetic crosses between the mutants and Yuwolcho or pungent lines indicated that a single recessive mutation was responsible for the low-pungency phenotype of mutant 221-2-1a; we named the causal locus Pungency 4 (Pun4). To identify Pun4, we combined genome-wide polymorphism analysis and transcriptome analysis with bulked-segregant analysis. We narrowed down the location of Pun4 to a 208-Mb region on chromosome 6 containing five candidate genes, of which DEMF06G16460, encoding a 3-ketoacyl-CoA synthase associated with branched-chain fatty acid biosynthesis, is the most likely candidate for Pun4. The expression of capsaicinoid biosynthetic genes in placental tissues in Yuwolcho and the mutant was consistent with the branched-chain fatty acid pathway playing a pivotal role in the lower pungency observed in the mutant. We also obtained a list of differentially expressed genes in placental tissues between the mutant and Yuwolcho, from which we selected candidate genes using gene co-expression analysis. In summary, we characterized the capsaicinoid biosynthesis-related locus Pun4 through integrated of genetic, genomic, and transcriptome analyses. These findings will contribute to our understanding of capsaicinoid biosynthesis in pepper.

Dual antiplatelet therapy de-escalation in acute coronary syndrome: an individual patient meta-analysis.

AIMS: Dual-antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is the standard treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). De-escalation of the potent P2Y12 inhibtor is an appealing concept to balance the ischaemic and bleeding risks after PCI. An individual patient data meta-analysis was performed to compare de-escalation versus standard DAPT in patients with ACS. METHODS AND RESULTS: Electronic databases, including PubMed, Embase, and the Cochrane database, were searched to identify randomised clinical trials (RCTs) comparing the de-escalation strategy with the standard DAPT after PCI in patients with ACS. Individual patient-level data were collected from the relevant trials. The co-primary endpoints of interest were the ischaemic composite endpoint (a composite of cardiac death, myocardial infarction, and cerebrovascular events) and bleeding endpoint (any bleeding) at 1-year post-PCI. Four RCTs (the TROPICAL-ACS, POPular Genetics, HOST-REDUCE-POLYTECH-ACS, and TALOS-AMI trials) including 10 133 patients were analysed. The ischaemic endpoint was significantly lower in the patients assigned to the de-escalation strategy than in those assigned to the standard strategy (2.3% vs. 3.0%, hazard ratio [HR] 0.761, 95% confidence interval [CI] 0.597-0.972, log rank P = 0.029). Bleeding was also significantly lower in the de-escalation strategy group (6.5% vs. 9.1%, HR 0.701, 95% CI 0.606-0.811, log rank P < 0.001). No significant intergroup differences were observed in terms of all-cause death and major bleeding events. Subgroup analyses revealed that compared to guided de-escalation, unguided de-escalation had a significantly larger impact on bleeding endpoint reduction (P for interaction = 0.007); no intergroup differences were observed for the ischaemic endpoints. CONCLUSION: In this individual patient data meta-analysis, DAPT-based de-escalation was associated with both decreased ischaemic and bleeding endpoints. Reduction in bleeding endpoints was more prominent for the unguided than the guided de-escalation strategy. STUDY REGISTRATION NUMBER: This study was registered in the PROSPERO (ID: CRD42021245477).

Efficacy and Safety of Triple Therapy of Telmisartan/Amlodipine/Rosuvastatin in Patients with Dyslipidemia and Hypertension: A Multicenter Randomized Clinical Trial.

Background: Hypertension and dyslipidemia significantly contribute to cardiovascular disease development. Their coexistence poses challenges in managing multiple medications, influencing treatment adherence. Objective: This study aimed to assess the efficacy and safety of a combined treatment approach using a fixed-dose combination therapy. Methods: This multicenter, 8-week, randomized, double-blind, Phase IV trial was named Telmisartan/Amlodipine/Rosuvastatin from Samjin Pharmaceuticals and evaluated the efficacy and safety of fixed-dose combination treatment in patients with essential hypertension and dyslipidemia. They were randomly assigned to 2 fixed-dose combination therapy groups, telmisartan 40 mg/amlodipine 5 mg/rosuvastatin 10 mg (TEL/ALD/RSV) or amlodipine 5 mg/atorvastatin 10 mg (ALD/ATV) after washout/run-in period. The primary outcomes were the change in mean sitting systolic blood pressure and the percentage change of LDL-C after 8 weeks of medical treatment. Adverse drug reactions and events were assessed. Results: Of a total of 304 patients who underwent screening, 252 were randomized to the TEL/ALD/RSV group (125 patients) and the ALD/ATV group (127 patients). The mean (SD) ages of the TEL/ALD/RSV group and the ALD/ATV group were 67.4 (11.3) and 68.2 (10.6) years, respectively (P = 0.563). The least-squares mean (SE) in mean sitting systolic blood pressure changes between the 2 groups were -16.27 (0.93) mm Hg in the TEL/ALD/RSV group, -6.85 (0.92) mm Hg in the ALD/ATV group (LSM difference = -9.42 mm Hg; 95% CI, -11.99 to -6.84; P < .001). For LDL-C level changes, a significant difference was noted between the 2 groups: -50.03% (1.18%) in the TEL/ALD/RSV group, -39.60% (1.17%) in the ALD/ATV group (LSM difference = -10.43%; 95% CI, -13.70 to -7.16; P < .001). No severe adverse events were observed. Conclusions: TEL/ALD/RSV proved to be more efficient than ALD/ATV in lowering blood pressure and reducing LDL-C levels among patients with hypertension and dyslipidemia, with no notable safety concerns. (Curr Ther Res Clin Exp. 2024; XX:XXX-XXX). ClinicalTrials.gov identifier: NCT03860220.

Safety and Efficacy of Everolimus-Eluting Bioresorbable Vascular Scaffold Versus Second-Generation Drug-Eluting Stents in Real-World Practice.

BACKGROUND: The risk of device thrombosis and device-oriented clinical outcomes with bioresorbable vascular scaffold (BVS) was reported to be significantly higher than with contemporary drug-eluting stents (DESs). However, optimal device implantation may improve clinical outcomes in patients receiving BVS. The current study evaluated mid-term safety and efficacy of Absorb BVS with meticulous device optimization under intravascular imaging guidance. METHODS: The SMART-REWARD and PERSPECTIVE-PCI registries in Korea prospectively enrolled 390 patients with BVS and 675 patients with DES, respectively. The primary endpoint was target vessel failure (TVF) at 2 years and the secondary major endpoint was patient-oriented composite outcome (POCO) at 2 years. RESULTS: Patient-level pooled analysis evaluated 1,003 patients (377 patients with BVS and 626 patients with DES). Mean scaffold diameter per lesion was 3.24 ± 0.30 mm in BVS group. Most BVSs were implanted with pre-dilatation (90.9%), intravascular imaging guidance (74.9%), and post-dilatation (73.1%) at proximal to mid segment (81.9%) in target vessel. Patients treated with BVS showed comparable risks of 2-year TVF (2.9% vs. 3.7%, adjusted hazard ratio [HR], 1.283, 95% confidence interval [CI], 0.487-3.378, P = 0.615) and 2-year POCO (4.5% vs. 5.9%, adjusted HR, 1.413, 95% CI, 0.663-3.012, P = 0.370) than those with DES. The rate of 2-year definite or probable device thrombosis (0.3% vs. 0.5%, P = 0.424) was also similar. The sensitivity analyses consistently showed comparable risk of TVF and POCO between the 2 groups. CONCLUSION: With meticulous device optimization under imaging guidance and avoidance of implantation in small vessels, BVS showed comparable risks of 2-year TVF and device thrombosis with DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02601404, NCT04265443.

Durable Polymer Versus Biodegradable Polymer Drug-Eluting Stents After Percutaneous Coronary Intervention in Patients with Acute Coronary Syndrome: The HOST-REDUCE-POLYTECH-ACS Trial.

BACKGROUND: Large-scale randomized comparison of drug-eluting stents (DES) based on durable polymer versus biodegradable polymer technology is currently insufficient in patients with acute coronary syndrome (ACS). The present study aimed to prove the noninferiority of the durable polymer DES (DP-DES) compared with the biodegradable polymer DES (BP-DES) in such patients. METHODS: The HOST-REDUCE-POLYTECH-ACS (Harmonizing Optimal Strategy for Treatment of Coronary Artery Diseases-Comparison of Reduction of Prasugrel Dose or Polymer Technology in ACS Patients) trial is an investigator-initiated, randomized, open-label, adjudicator-blinded, multicenter, noninferiority trial comparing the efficacy and safety of DP-DES and BP-DES in patients with ACS. The primary end point was a patient-oriented composite outcome (a composite of all-cause death, nonfatal myocardial infarction, and any repeat revascularization) at 12 months. The key secondary end point was device-oriented composite outcome (a composite of cardiac death, target-vessel myocardial infarction, or target lesion revascularization) at 12 months. RESULTS: A total of 3413 patients were randomized to receive the DP-DES (1713 patients) and BP-DES (1700 patients). At 12 months, patient-oriented composite outcome occurred in 5.2% in the DP-DES group and 6.4% in the BP-DES group (absolute risk difference, -1.2%; Pnoninferiority<0.001). The key secondary end point, device-oriented composite outcome, occurred less frequently in the DP-DES group (DP-DES vs BP-DES, 2.6% vs 3.9%; hazard ratio, 0.67 [95% CI, 0.46-0.98]; P=0.038), mostly because of a reduction in target lesion revascularization. The rate of spontaneous nonfatal myocardial infarction and stent thrombosis were extremely low, with no significant difference between the 2 groups (0.6% versus 0.8%; P=0.513 and 0.1% versus 0.4%; P=0.174, respectively). CONCLUSIONS: In ACS patients receiving percutaneous coronary intervention, DP-DES was noninferior to BP-DES with regard to patient-oriented composite outcomes at 12 months after index percutaneous coronary intervention. Registration: URL: https://wwwclinicaltrials.gov; Unique identifier: NCT02193971.

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.

Angiographic complete revascularization versus incomplete revascularization in patients with diabetes mellitus.

BACKGROUND: Considering the nature of diabetes mellitus (DM) in coronary artery disease, it is unclear whether complete revascularization is beneficial or not in patients with DM. We investigated the clinical impact of angiographic complete revascularization in patients with DM. METHODS: A total of 5516 consecutive patients (2003 patients with DM) who underwent coronary stenting with 2nd generation drug-eluting stent were analyzed. Angiographic complete revascularization was defined as a residual SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score of 0. The patient-oriented composite outcome (POCO, including all-cause death, any myocardial infarction, and any revascularization) and target lesion failure (TLF) at three years were analyzed. RESULTS: Complete revascularization was associated with a reduced risk of POCO in DM population [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.52-0.93, p = 0.016], but not in non-DM population (adjusted HR 0.90, 95% CI 0.69-1.17, p = 0.423). The risk of TLF was comparable between the complete and incomplete revascularization groups in both DM (adjusted HR 0.75, 95% CI 0.49-1.16, p = 0.195) and non-DM populations (adjusted HR 1.11, 95% CI 0.75-1.63, p = 0.611). The independent predictors of POCO were incomplete revascularization, multivessel disease, left main disease and low ejection fraction in the DM population, and old age, peripheral vessel disease, and low ejection fraction in the non-DM population. CONCLUSIONS: The clinical benefit of angiographic complete revascularization is more prominent in patients with DM than those without DM after three years of follow-up. Relieving residual disease might be more critical in the DM population than the non-DM population. Trial registration The Grand Drug-Eluting Stent registry NCT03507205.

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.

Determination of [N-13]-ammonia extraction fraction in patients with coronary artery disease by calibration to invasive coronary and fractional flow reserve.

BACKGROUND: This study presents a new extraction fraction (EF) model based on physiological measures of invasive coronary flow reserve (CFR) and fractional flow reserve (FFR) in patients with suspected coronary artery disease (CAD) and normal index microcirculatory resistance (IMR). To ascertain the clinical relevance of the new EFs, flow measurements using the newly patient-determined EFs were compared to flow measurements using traditional animal-determined EFs. METHODS: 39 patients were retrospectively selected that included a total of 91 vascular territories with invasive coronary angiography physiological measures. [N-13]-ammonia dynamic rest/adenosine-stress PET imaging was conducted in all patients and absolute myocardial flow was estimated using four published compartmental models. The extraction fraction during hyperemic flow was iteratively estimated by maximizing the agreement between invasive CFR and FFR with the non-invasive analogs myocardial flow reserve (MFR) and relative flow reserve (RFR) at similar physiological states, respectively. RESULTS: Using the new patient-determined EFs, agreement between CFR vs MFR for Model 1 and 2 was moderate and poor for Model 3 and 4. All models showed moderate agreement for FFR vs RFR. When using published models of animal-determined EFs, agreement between CFR vs MFR remained moderate for Model 1 and 2, and poor for Model 3 and 4. Similarly, all models showed moderate agreement for FFR vs RFR using animal-determined EF values. None of the observed differences were statistically significant. CONCLUSIONS: Flow measurements using extraction fraction correction for [N-13]-ammonia based on calibration to invasive intracoronary angiography physiological measures in patients with CAD were not discordant from those reported in the literature. Either patient-determined or traditional animal-determined EF correction, when used with the appropriate flow model, yields moderate agreement with invasive measurements of coronary flow reserve and fractional flow reserve.

Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial.

BACKGROUND: A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy. METHODS: HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971. RESULTS: From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference -2·9%, pnon-inferiority<0·0001; hazard ratio 0·70 [95% CI 0·52-0·92], pequivalence=0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 [0·40-1·45]; p=0·40), and the risk of bleeding events was significantly decreased (0·48 [0·32-0·73]; p=0·0007). INTERPRETATION: In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia. FUNDING: Daiichi Sankyo, Boston Scientific, Terumo, Biotronik, Qualitech Korea, and Dio.

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.

Analysis of risk factors for delayed bleeding after semi-closed hemorrhoidectomy.

PURPOSE: The aim of this study was to determine the incidence of delayed post-hemorrhoidectomy bleeding (DPHB) after hemorrhoidectomy using a semi-closed procedure. We also investigated risk factors associated with DPHB. METHODS: This retrospective study enrolled a total of 1645 consecutive patients with symptomatic grade II to IV hemorrhoids who underwent a semi-closed procedure at the Seoul Songdo Hospital between September 2018 and May 2019. All patients underwent a semi-closed procedure with submucosal feeding vessel ligation, a method commonly performed at our institution. RESULTS: A total of 1645 patients (mean age: 48.67 (±14.38) years, 823 (50.0%) male/822 (50.0%) female) underwent semi-closed hemorrhoidectomy. Critically, 24 (1.5%) patients experienced DPHB. Of these patients, 13 (0.8%) experienced stump bleeding, whereas 11 (0.7%) experienced marginal bleeding. The mean bleeding period was 8.21±4.45 days. Multivariate analysis showed that male sex, drinking history, more than four hemorrhoid piles, and laxative agents were independent risk factors for DPHB. The risk of stump bleeding was significantly associated with male sex (OR=5.55, 95% CI 1.23-25.14, p=0.026), more than four hemorrhoid piles (OR=5.90, 95% CI 1.62-21.53, p=0.007), and laxative usage (OR=3.92, 95% CI 1.31-11.74, p=0.015). Conversely, the risk of marginal bleeding were significantly associated with drinking history (OR=10.48, 95% CI 1.34-82.03, p=0.025) and more than four hemorrhoid piles (OR=4.71, 95% CI 1.24-17.81, p=0.023). CONCLUSION: Male sex, drinking history, more than four hemorrhoid piles, and laxative usage were independent risk factors for DPHB in patients undergoing semi-closed hemorrhoidectomy. The risk factors for stump bleeding included male sex, more than four hemorrhoid piles, and laxative usage. In contrast, the risk factors for marginal bleeding were drinking history and more than four hemorrhoid piles.

Physiological and Clinical Assessment of Resting Physiological Indexes.

BACKGROUND: Recently, resting pressure-derived indexes such as resting full-cycle ratio (RFR) and diastolic pressure ratio (dPR) have been introduced to assess the functional significance of epicardial coronary stenosis. The present study sought to investigate the agreement of RFR or dPR with other pressure-derived indexes (instantaneous wave-free ratio [iFR] or fractional flow reserve), the sensitivity of RFR or dPR for anatomic or hemodynamic stenosis severity, and the prognostic implications of RFR or dPR compared with iFR Methods: RFR and dPR were calculated from resting pressure tracings by an independent core laboratory in 1024 vessels (435 patients). The changes in resting physiological indexes according to diameter stenosis were compared among iFR, RFR, and dPR. Among 115 patients who underwent 13N-ammonia positron emission tomography, the changes in those indexes according to basal and hyperemic stenosis resistance and absolute hyperemic myocardial blood flow were compared. The association between resting physiological indexes and the risk of 2-year vessel-oriented composite outcomes (a composite of cardiac death, vessel-related myocardial infarction, and vessel-related ischemia-driven revascularization) was analyzed among 864 deferred vessels. RESULTS: Both RFR and dPR showed a significant correlation with iFR ( R=0.979, P<0.001 for RFR; and R=0.985, P<0.001 for dPR), which was higher than that with fractional flow reserve ( R=0.822, P<0.001; and R=0.819, P<0.001, respectively). RFR and dPR showed a very high agreement with iFR (C index, 0.987 and 0.993). Percent difference of iFR, RFR, and dPR according to the increase in anatomic and hemodynamic severity was almost identical. The diagnostic performance of iFR, RFR, and dPR was not different in the prediction of myocardial ischemia defined by both low hyperemic myocardial blood flow and low coronary flow reserve by 13N-ammonia positron emission tomography. All resting physiological indexes showed significant association with the risk of 2-year vessel-oriented composite outcomes (iFR per 0.1 increase: hazard ratio, 0.514 [95% CI, 0.370-0.715], P<0.001; RFR per 0.1 increase: hazard ratio, 0.524 [95% CI, 0.378-0.725], P<0.001; dPR per 0.1 increase: hazard ratio, 0.587 [95% CI, 0.436-0.791], P<0.001) in deferred vessels. CONCLUSIONS: All resting pressure-derived physiological indexes (iFR, RFR, and dPR) can be used as invasive tools to guide treatment strategy in patients with coronary artery disease. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01621438.

Relevance of anatomical, plaque, and hemodynamic characteristics of non-obstructive coronary lesions in the prediction of risk for acute coronary syndrome.

OBJECTIVES: We explored the anatomical, plaque, and hemodynamic characteristics of high-risk non-obstructive coronary lesions that caused acute coronary syndrome (ACS). METHODS: From the EMERALD study which included ACS patients with available coronary CT angiography (CCTA) before the ACS, non-obstructive lesions (percent diameter stenosis < 50%) were selected. CCTA images were analyzed for lesion characteristics by independent CCTA and computational fluid dynamics core laboratories. The relative importance of each characteristic was assessed by information gain. RESULTS: Of the 132 lesions, 24 were the culprit for ACS. The culprit lesions showed a larger change in FFRCT across the lesion (ΔFFRCT) than non-culprit lesions (0.08 ± 0.07 vs 0.05 ± 0.05, p = 0.012). ΔFFRCT showed the highest information gain (0.051, 95% confidence interval [CI] 0.050-0.052), followed by low-attenuation plaque (0.028, 95% CI 0.027-0.029) and plaque volume (0.023, 95% CI 0.022-0.024). Lesions with higher ΔFFRCT or low-attenuation plaque showed an increased risk of ACS (hazard ratio [HR] 3.25, 95% CI 1.31-8.04, p = 0.010 for ΔFFRCT; HR 2.60, 95% CI 1.36-4.95, p = 0.004 for low-attenuation plaque). The prediction model including ΔFFRCT, low-attenuation plaque and plaque volume showed the highest ability in ACS prediction (AUC 0.725, 95% CI 0.724-0.727). CONCLUSION: Non-obstructive lesions with higher ΔFFRCT or low-attenuation plaque showed a higher risk of ACS. The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk in non-obstructive lesions. KEY POINTS: • Change in FFR CT across the lesion (ΔFFR CT ) was the most important predictor of ACS risk in non-obstructive lesions. • Non-obstructive lesions with higher ΔFFR CT or low-attenuation plaque were associated with a higher risk of ACS. • The integration of anatomical, plaque, and hemodynamic characteristics can improve the noninvasive prediction of ACS risk.

Clinical Outcome of Lesions With Discordant Results Among Different Invasive Physiologic Indices　- Resting Distal Coronary to Aortic Pressure Ratio, Resting Full-Cycle Ratio, Diastolic Pressure Ratio, Instantaneous Wave-Free Ratio, and Fractional Flow Reserve.

BACKGROUND: We evaluated the 2-year clinical outcomes of deferred lesions with discordant results between resting and hyperemic pressure-derived physiologic indices, including resting distal to aortic coronary pressure (resting Pd/Pa), instantaneous wave-free ratio (iFR), resting full-cycle ratio (RFR), diastolic pressure ratio (dPR), and fractional flow reserve (FFR).Methods and Results:The 2-year clinical outcomes of 1,024 vessels (435 patients) with available resting Pd/Pa, iFR, RFR, dPR, and FFR data were analyzed according to a 4-group classification using known cutoff values (resting Pd/Pa ≤0.92, iFR/RFR/dPR ≤0.89, and FFR ≤0.80): Group 1 (concordant normal), Group 2 (high resting index and low FFR), Group 3 (low resting index and high FFR), and Group 4 (concordance abnormal). The primary outcome was vessel-oriented composite outcomes (VOCO) in deferred vessels at 2 years. In the comparison of VOCO risk among 4 groups classified according to FFR and 4 resting physiologic indices, Group 4 consistently showed a significantly higher risk of VOCO than Group 1. Comparison of VOCO risk among 4 groups classified according to iFR and other resting physiologic indices also showed the same results. The presence of discordance, either between hyperemic and resting indices or among resting indices, was not an independent predictor for VOCO. CONCLUSIONS: Discordant results between resting physiologic indices and FFR and among the resting indices were not associated with increased risk of VOCO in deferred lesions.

Prognostic Impact of ß-Blocker Dose After Acute Myocardial Infarction.

BACKGROUND: The differential prognostic impact of ß-blocker dose after acute myocardial infarction (AMI) has been under debate. The current study sought to compare clinical outcome after AMI according to ß-blocker dose using the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH). Methods and Results: Of the total population of 13,104 consecutive AMI patients enrolled in the KAMIR-NIH, the current study analyzed 11,909 patients. These patients were classified into 3 groups (no ß-blocker; low-dose [<25% of target dose]; and high-dose [≥25% of target dose]). The primary outcome was cardiac death at 1 year. Compared with the no ß-blocker group, both the low-dose and high-dose groups had significantly lower risk of cardiac death (HR, 0.435; 95% CI: 0.363-0.521, P<0.001; HR, 0.519; 95% CI: 0.350-0.772, P=0.001, respectively). The risk of cardiac death, however, was similar between the high- and low-dose groups (HR, 1.194; 95% CI: 0.789-1.808, P=0.402). On multivariable adjustment and inverse probability weighted analysis, the result was the same. CONCLUSIONS: The use of ß-blockers in post-AMI patients had significant survival benefit compared with no use of ß-blockers. There was no significant additional benefit of high-dose ß-blockers compared with low-dose ß-blockers, however, in terms of 1-year risk of cardiac death.