Clinical Value of Single-Projection Angiography-Derived FFR in Noninfarct-Related Artery.

BACKGROUND: The Murray law-based quantitative flow ratio (µFR) is an emerging technique that requires only 1 projection of coronary angiography with similar accuracy to quantitative flow ratio (QFR). However, it has not been validated for the evaluation of noninfarct-related artery (non-IRA) in acute myocardial infarction (AMI) settings. Therefore, our study aimed to evaluate the diagnostic accuracy of µFR and the safety of deferring non-IRA lesions with µFR >0.80 in the setting of AMI. METHODS: µFR and QFR were analyzed for non-IRA lesions of patients with AMI enrolled in the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infarction Related Artery Stenosis in Patients With Acute Myocardial Infarction), consisting of fractional flow reserve (FFR)-guided percutaneous coronary intervention and angiography-guided percutaneous coronary intervention groups. The diagnostic accuracy of µFR was compared with QFR and FFR. Patients were classified by the non-IRA µFR value of 0.80 as a cutoff value. The primary outcome was a vessel-oriented composite outcome, a composite of cardiac death, non-IRA-related myocardial infarction, and non-IRA-related repeat revascularization. RESULTS: µFR and QFR analyses were feasible in 443 patients (552 lesions). µFR showed acceptable correlation with FFR (R=0.777; P<0.001), comparable C-index with QFR to predict FFR ≤0.80 (µFR versus QFR: 0.926 versus 0.961, P=0.070), and shorter total analysis time (mean, 32.7 versus 186.9 s; P<0.001). Non-IRA with µFR >0.80 and deferred percutaneous coronary intervention had a significantly lower risk of vessel-oriented composite outcome than non-IRA with performed percutaneous coronary intervention (3.4% versus 10.5%; hazard ratio, 0.37 [95% CI, 0.14-0.99]; P=0.048). CONCLUSIONS: In patients with multivessel AMI, µFR of non-IRA showed acceptable diagnostic accuracy comparable to that of QFR to predict FFR ≤0.80. Deferred non-IRA with µFR >0.80 showed a lower risk of vessel-oriented composite outcome than revascularized non-IRA. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Long-acting cilostazol versus isosorbide mononitrate for patients with vasospastic angina: a randomized controlled trial.

BACKGROUND: Cilostazol has a vasodilatory function that may be beneficial for patients with vasospastic angina (VSA). We conducted a randomized, open-label, controlled trial to compare the efficacy and safety of long-acting cilostazol and isosorbide mononitrate (ISMN) for VSA. METHODS: The study included patients with confirmed VSA between September 2019 and May 2021. Participants were randomly assigned to receive long-acting cilostazol (test group, 200 mg once daily) or conventional ISMN therapy (control group, 20 mg twice daily) for 4 weeks. The clinical efficacy and safety were evaluated using weekly questionnaires. RESULTS: Forty patients were enrolled in the study (long-acting cilostazol, n = 20; ISMN, n = 20). Baseline characteristics were balanced between the two groups. Long acting cilostazol showed better angina symptom control within the first week compared to ISMN [reduction of pain intensity score, 6.0 (4.0-8.0) vs. 4.0 (1.0-5.0), P = 0.005; frequency of angina symptom, 0 (0-2.0) vs. 2.0 (0-3.0), P = 0.027, respectively]. The rate of neurological adverse reactions was lower in the cilostazol group than in the ISMN group (headache or dizziness, 40 vs. 85%, P = 0.009; headache, 30 vs. 70%, P = 0.027). CONCLUSION: Long-acting cilostazol provided comparable control of angina and fewer adverse neurologic reactions within 4 weeks compared to ISMN. Long-acting cilostazol provides more intensive control of angina within 1 week, suggesting that it may be an initial choice for the treatment of VSA.

Intravascular Imaging-Guided Optimization of Complex Percutaneous Coronary Intervention by Sex: A Subgroup Analysis of the RENOVATE-COMPLEX-PCI Trial.

Importance: There have been heterogeneous results related to sex differences in prognosis after percutaneous coronary artery intervention (PCI) for complex coronary artery lesions. Objective: To evaluate potential differences in outcomes with intravascular imaging-guided PCI of complex coronary artery lesions between women and men. Design, Setting, and Participants: This prespecified substudy evaluates the interaction of sex in the investigator-initiated, open-label, multicenter RENOVATE-COMPLEX-PCI randomized clinical trial, which demonstrated the superiority of intravascular imaging-guided PCI compared with angiography-guided PCI in patients with complex coronary artery lesions. The trial was conducted at 20 sites in Korea. Patients with complex coronary artery lesions undergoing PCI were enrolled between May 2018 and May 2021, and the median (IQR) follow-up period was 2.1 (1.4-3.0) years. Data were analyzed from December 2022 to December 2023. Interventions: After diagnostic coronary angiography, eligible patients were randomly assigned in a 2:1 ratio to receive intravascular imaging-guided PCI or angiography-guided PCI. The choice and timing of the intravascular imaging device were left to the operators' discretion. Main Outcomes and Measures: The primary end point was target vessel failure, defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. Secondary end points included individual components of the primary end point. Results: Of 1639 included patients, 339 (20.7%) were women, and the mean (SD) age was 65.6 (10.2) years. There was no difference in the risk of the primary end point between women and men (9.4% vs 8.3%; adjusted hazard ratio [HR], 1.39; 95% CI, 0.89-2.18; P = .15). Intravascular imaging-guided PCI tended to have lower incidence of the primary end point than angiography-guided PCI in both women (5.2% vs 14.5%; adjusted HR, 0.34; 95% CI, 0.15-0.78; P = .01) and men (8.3% vs 11.7%; adjusted HR, 0.72; 95% CI, 0.49-1.05; P = .09) without significant interaction (P for interaction = .86). Conclusions and Relevance: In patients undergoing complex PCI, compared with angiographic guidance, intravascular imaging guidance was associated with similar reduction in the risk of target vessel failure among women and men. The treatment benefit of intravascular imaging-guided PCI showed no significant interaction between treatment strategy and sex. Trial Registration: ClinicalTrials.gov Identifier: NCT03381872.

Cost-Effectiveness of Fractional Flow Reserve-Guided Treatment for Acute Myocardial Infarction and Multivessel Disease: A Prespecified Analysis of the FRAME-AMI Randomized Clinical Trial.

Importance: Complete revascularization by non-infarct-related artery (IRA) percutaneous coronary intervention (PCI) in patients with acute myocardial infarction is standard practice to improve patient prognosis. However, it is unclear whether a fractional flow reserve (FFR)-guided or angiography-guided treatment strategy for non-IRA PCI would be more cost-effective. Objective: To evaluate the cost-effectiveness of FFR-guided compared with angiography-guided PCI in patients with acute myocardial infarction and multivessel disease. Design, Setting, and Participants: In this prespecified cost-effectiveness analysis of the FRAME-AMI randomized clinical trial, patients were randomly allocated to either FFR-guided or angiography-guided PCI for non-IRA lesions between August 19, 2016, and December 24, 2020. Patients were aged 19 years or older, had ST-segment elevation myocardial infarction (STEMI) or non-STEMI and underwent successful primary or urgent PCI, and had at least 1 non-IRA lesion (diameter stenosis >50% in a major epicardial coronary artery or major side branch with a vessel diameter of ≥2.0 mm). Data analysis was performed on August 27, 2023. Intervention: Fractional flow reserve-guided vs angiography-guided PCI for non-IRA lesions. Main Outcomes and Measures: The model simulated death, myocardial infarction, and repeat revascularization. Future medical costs and benefits were discounted by 4.5% per year. The main outcomes were quality-adjusted life-years (QALYs), direct medical costs, incremental cost-effectiveness ratio (ICER), and incremental net monetary benefit (INB) of FFR-guided PCI compared with angiography-guided PCI. State-transition Markov models were applied to the Korean, US, and European health care systems using medical cost (presented in US dollars), utilities data, and transition probabilities from meta-analysis of previous trials. Results: The FRAME-AMI trial randomized 562 patients, with a mean (SD) age of 63.3 (11.4) years. Most patients were men (474 [84.3%]). Fractional flow reserve-guided PCI increased QALYs by 0.06 compared with angiography-guided PCI. The total cumulative cost per patient was estimated as $1208 less for FFR-guided compared with angiography-guided PCI. The ICER was -$19 484 and the INB was $3378, indicating that FFR-guided PCI was more cost-effective for patients with acute myocardial infarction and multivessel disease. Probabilistic sensitivity analysis showed consistent results and the likelihood iteration of cost-effectiveness in FFR-guided PCI was 97%. When transition probabilities from the pairwise meta-analysis of the FLOWER-MI and FRAME-AMI trials were used, FFR-guided PCI was more cost-effective than angiography-guided PCI in the Korean, US, and European health care systems, with an INB of $3910, $8557, and $2210, respectively. In probabilistic sensitivity analysis, the likelihood iteration of cost-effectiveness with FFR-guided PCI was 85%, 82%, and 31% for the Korean, US, and European health care systems, respectively. Conclusions and Relevance: This cost-effectiveness analysis suggests that FFR-guided PCI for non-IRA lesions saved medical costs and increased quality of life better than angiography-guided PCI for patients with acute myocardial infarction and multivessel disease. Fractional flow reserve-guided PCI should be considered in determining the treatment strategy for non-IRA stenoses in these patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02715518.

Angiographic Severity of the Nonculprit Lesion and the Efficacy of Fractional Flow Reserve-Guided Complete Revascularization in Patients With AMI: FRAME-AMI Substudy.

BACKGROUND: The benefit of fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) for noninfarct-related artery (IRA) lesions with angiographically severe stenosis in patients with acute myocardial infarction is unclear. METHODS: Among 562 patients from the FRAME-AMI trial (Fractional Flow Reserve Versus Angiography-Guided Strategy for Management of Non-Infraction Related Artery Stenosis in Patients With Acute Myocardial Infarction) who were randomly allocated into either FFR-guided or angiography-guided PCI for non-IRA lesions, the current study evaluated the relationship between non-IRA stenosis measured by quantitative coronary angiography (QCA) and the efficacy of FFR-guided PCI. The incidence of the primary end point (death, myocardial infarction, or repeat revascularization) was compared between FFR- and angiography-guided PCI according to non-IRA stenosis severity (QCA stenosis ≥70% or <70%). RESULTS: A total of 562 patients were assigned to FFR-guided (n=284) versus angiography-guided PCI (n=278). At a median follow-up of 3.5 years, the primary end point occurred in 14 of 181 patients with FFR-guided PCI and 31 of 197 patients with angiography-guided PCI among patients with QCA stenosis ≥70% (8.5% versus 19.2%; hazard ratio, 0.41 [95% CI, 0.22-0.80]; P=0.008), while occurred in 4 of 103 patients with FFR-guided PCI and 9 of 81 patients with angiography-guided PCI among those with QCA stenosis <70% (3.9% versus 11.1%; P=0.315). There was no significant interaction between treatment strategy and non-IRA stenosis severity (P for interaction=0.636). FFR-guided PCI was associated with the reduction of death and myocardial infarction in both patients with QCA stenosis ≥70% (6.7% versus 15.1%; P=0.008) and those with QCA stenosis <70% (1.0% versus 9.6%; P=0.042) compared with angiography-guided PCI. CONCLUSIONS: In patients with acute myocardial infarction and multivessel disease, FFR-guided PCI tended to have a lower risk of primary end point than angiography-guided PCI regardless of non-IRA stenosis severity without significant interaction. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02715518.

Clinical Benefit of Intravascular Imaging Compared With Conventional Angiography in Left Main Coronary Artery Intervention.

BACKGROUND: The RENOVATE-COMPLEX-PCI (Randomized Controlled Trial of Intravascular Imaging Guidance Versus Angiography-Guidance on Clinical Outcomes After Complex Percutaneous Coronary Intervention) demonstrated that intravascular imaging-guided percutaneous coronary intervention (PCI) improved clinical outcome compared with angiography-guided PCI for patients with complex coronary artery lesions. This study aims to assess whether the prognostic benefit of intravascular imaging-guided procedural optimization persists in patients undergoing PCI for left main coronary artery disease. METHODS: Of 1639 patients enrolled in the RENOVATE-COMPLEX-PCI, 192 patients with left main coronary artery disease were selected for the current prespecified substudy. Selected patients were randomly assigned to either the intravascular imaging-guided PCI group (n=138) or the angiography-guided PCI group (n=54). The primary end point was target vessel failure defined as a composite of cardiac death, target vessel-related myocardial infarction, or clinically driven target vessel revascularization. RESULTS: At a median follow-up of 2.1 years (interquartile range 1.1 to 3.0 years), intravascular imaging-guided PCI was associated with lower incidence of primary end point compared with angiography-guided PCI (6.8% versus 25.1%; hazard ratio, 0.31 [95% CI, 0.13-0.76]; P=0.010). This significant reduction in primary end point was mainly driven by a lower risk of cardiac death or spontaneous target vessel-related myocardial infarction (1.6% versus 12.7%; hazard ratio, 0.16 [95% CI, 0.03-0.82]; P=0.028). Intravascular imaging-guided PCI was independently associated with a lower risk of primary end point, even after adjusting for various clinical factors (hazard ratio, 0.29 [95% CI, 0.12-0.72]; P=0.007). CONCLUSIONS: Intravascular imaging-guided PCI showed clinical benefit over angiography-guided PCI for left main coronary artery disease in reducing the risk of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03381872.

QFR Assessment and Prognosis After Nonculprit PCI in Patients With Acute Myocardial Infarction.

BACKGROUND: Complete revascularization using either angiography-guided or fractional flow reserve (FFR)-guided strategy can improve clinical outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, there is concern that angiography-guided percutaneous coronary intervention (PCI) may result in un-necessary PCI of the non-infarct-related artery (non-IRA), and its long-term prognosis is still unclear. OBJECTIVES: This study sought to evaluate clinical outcomes after non-IRA PCI according to the quantitative flow ratio (QFR). METHODS: We performed post hoc QFR analysis of non-IRA lesions of AMI patients enrolled in the FRAME-AMI (FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease) trial, which randomly allocated 562 patients into either FFR-guided PCI (FFR ≤0.80) or angiography-guided PCI (diameter stenosis >50%) for non-IRA lesions. Patients were classified by non-IRA QFR values into the QFR ≤0.80 and QFR >0.80 groups. The primary outcome was a major adverse cardiac event (MACE), a composite of cardiac death, myocardial infarction, and repeat revascularization. RESULTS: A total of 443 patients (552 lesions) were eligible for QFR analysis. Of 209 patients in the angiography-guided PCI group, 30.0% (n = 60) underwent non-IRA PCI despite having QFR >0.80 in the non-IRA. Conversely, only 2.7% (n = 4) among 209 patients in the FFR-guided PCI group had QFR >0.80 in the non-IRA. At a median follow-up of 3.5 years, the rate of MACEs was significantly higher among patients with non-IRA PCI despite QFR >0.80 than in patients with deferred PCI for non-IRA lesions (12.9% vs 3.1%; HR: 4.13; 95% CI: 1.10-15.57; P = 0.036). Non-IRA PCI despite QFR >0.80 was associated with a higher risk of non-IRA MACEs than patients with deferred PCI for non-IRA lesions (12.9% vs 2.1%; HR: 5.44; 95% CI: 1.13-26.19; P = 0.035). CONCLUSIONS: In AMI patients with multivessel disease, 30.0% of angiography-guided PCI resulted in un-necessary PCI for the non-IRA with QFR >0.80, which was significantly associated with an increased risk of MACEs than in those with deferred PCI for non-IRA lesions. (FFR Versus Angiography-Guided Strategy for Management of AMI With Multivessel Disease [FRAME-AMI] ClinicalTrials.gov number; NCT02715518).

Impact of height difference between coronary ostium and location of intracoronary pressure sensor on fractional flow reserve measurements.

BACKGROUND: During fractional flow reserve (FFR) measurements, distal coronary pressure (Pd) can be influenced by hydrostatic pressure changes resulting from the height difference (HD) between the coronary ostium and the location of the distal pressure sensor. AIMS: We investigated the effect of aortocoronary HD on the FFR measurements in each coronary artery. METHODS: In this retrospective cohort study, we analyzed 257 patients who underwent FFR measurements and coronary computed tomography (CCTA) within a year. Using CCTA, we measured HD as the vertical distance between the coronary ostium and a matched point of the distal coronary pressure sensor identified on coronary angiography. RESULTS: The location of the Pd sensor was higher than the coronary ostium in the left anterior descending artery (LAD) (-4.64 ± 1.15 cm) and lower than the coronary ostium in the left circumflex artery (LCX) (2.54 ± 1.05 cm) and right coronary artery (RCA) (2.03 ± 1.28 cm). The corrected FFR values by HD were higher in the LAD (0.78 ± 0.09 to 0.82 ± 0.09, P<0.01) and lower in the LCX and RCA than the original FFR values (0.87 ± 0.07 to 0.85 ± 0.08, P<0.01; 0.87 ± 0.10 to 0.86 ± 0.10, P<0.01, respectively). Using an FFR cut-off value of 0.8, the concordance rates between the FFR and corrected FFR values were 77.8%, 95.2%, and 100% in the LAD, LCX, and RCA, respectively. CONCLUSION: HD between the coronary ostium and the distal coronary pressure sensor may affect FFR measurements and FFR-guided treatment decisions for coronary artery disease.

Role and Clinical Importance of Progressive Changes in Echocardiographic Parameters in Predicting Outcomes in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The prognostic utility of follow-up transthoracic echocardiography (FU-TTE) in patients with hypertrophic cardiomyopathy (HCM) is unclear, specifically in terms of whether changes in echocardiographic parameters in routine FU-TTE parameters are associated with cardiovascular outcomes. METHODS: From 2010 to 2017, 162 patients with HCM were retrospectively enrolled in this study. Using echocardiography, HCM was diagnosed based on morphological criteria. Patients with other diseases that cause cardiac hypertrophy were excluded. TTE parameters at baseline and FU were analyzed. FU-TTE was designated as the last recorded value in patients who did not develop any cardiovascular event or the latest exam before event development. Clinical outcomes were acute heart failure, cardiac death, arrhythmia, ischemic stroke, and cardiogenic syncope. RESULTS: Median interval between the baseline TTE and FU-TTE was 3.3 years. Median clinical FU duration was 4.7 years. Septal trans-mitral velocity/mitral annular tissue Doppler velocity (E/e'), tricuspid regurgitation velocity, left ventricular ejection fraction (LVEF), and left atrial volume index (LAVI) at baseline were recorded. LVEF, LAVI, and E/e' values were associated with poor outcomes. However, no delta values predicted HCM-related cardiovascular outcomes. Logistic regression models incorporating changes in TTE parameters had no significant findings. Baseline LAVI was the best predictor of a poor prognosis. In survival analysis, an already enlarged or increased size LAVI was associated with poorer clinical outcomes. CONCLUSIONS: Changes in echocardiographic parameters extracted from TTE did not assist in predicting clinical outcomes. Cross-sectionally evaluated TTE parameters were superior to changes in TTE parameters between baseline and FU at predicting cardiovascular events.

Influence of an abnormal ankle-brachial index on ischemic and bleeding events in patients undergoing percutaneous coronary intervention.

BACKGROUND/AIMS: Bleeding events after percutaneous coronary intervention (PCI) have important prognostic implications. Data on the influence of an abnormal ankle-brachial index (ABI) on both ischemic and bleeding events in patients undergoing PCI are limited. METHODS: We included patients who underwent PCI with available ABI data (abnormal ABI, ≤ 0.9 or > 1.4). The primary endpoint was the composite of all-cause death, myocardial infarction (MI), stroke, and major bleeding. RESULTS: Among 4,747 patients, an abnormal ABI was observed in 610 patients (12.9%). During follow-up (median, 31 months), the 5-year cumulative incidence of adverse clinical events was higher in the abnormal ABI group than in the normal ABI group: primary endpoint (36.0% vs. 14.5%, log-rank test, p < 0.001); all-cause death (19.4% vs. 5.1%, log-rank test, p < 0.001); MI (6.3% vs. 4.1%, log-rank test, p = 0.013); stroke (6.2% vs. 2.7%, log-rank test, p = 0.001); and major bleeding (8.9% vs. 3.7%, log-rank test, p < 0.001). An abnormal ABI was an independent risk factor for all-cause death (hazard ratio [HR], 3.05; p < 0.001), stroke (HR, 1.79; p = 0.042), and major bleeding (HR, 1.61; p = 0.034). CONCLUSION: An abnormal ABI is a risk factor for both ischemic and bleeding events after PCI. Our study findings may be helpful in determining the optimal method for secondary prevention after PCI.

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).

Prognostic impact of hypercoagulability and impaired fibrinolysis in acute myocardial infarction.

AIMS: Atherothrombotic events are influenced by systemic hypercoagulability and fibrinolytic activity. The present study evaluated thrombogenicity indices and their prognostic implications according to disease acuity. METHODS AND RESULTS: From the consecutive patients undergoing percutaneous coronary intervention (PCI), those with thrombogenicity indices (n = 2705) were grouped according to disease acuity [acute myocardial infarction (AMI) vs. non-AMI]. Thrombogenicity indices were measured by thromboelastography (TEG). Blood samples for TEG were obtained immediately after insertion of the PCI sheath, and TEG tracing was performed within 4 h post-sampling. Major adverse cardiovascular events (MACE, a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke) were evaluated for up to 4 years. Compared with non-AMI patients, AMI patients had higher platelet-fibrin clot strength [maximal amplitude (MA): 66.5 ± 7.8 vs. 65.3 ± 7.2 mm, P < 0.001] and lower fibrinolytic activity [clot lysis at 30 min (LY30): 0.9 ± 1.8% vs. 1.1 ± 1.9%, P < 0.001]. Index AMI presentation was associated with MA [per one-mm increase: odds ratio (OR): 1.024; 95% confidence interval (CI): 1.013-1.036; P < 0.001] and LY30 (per one% increase: OR: 0.934; 95% CI: 0.893-0.978; P = 0.004). The presence of high platelet-fibrin clot strength (MA ≥68 mm) and low fibrinolytic activity (LY30 < 0.2%) was synergistically associated with MACE occurrence. In the multivariable analysis, the combined phenotype of 'MA ≥ 68 mm' and 'LY30 < 0.2%' was a major predictor of post-PCI MACE in the AMI group [adjusted hazard ratio (HR): 1.744; 95% CI: 1.135-2.679; P = 0.011], but not in the non-AMI group (adjusted HR: 1.031; 95% CI: 0.499-2.129; P = 0.935). CONCLUSION: AMI occurrence is significantly associated with hypercoagulability and impaired fibrinolysis. Their combined phenotype increases the risk of post-PCI atherothrombotic event only in AMI patients. These observations may support individualized therapy that targets thrombogenicity for better outcomes in patients with AMI. CLINICAL TRIAL REGISTRATION: Gyeongsang National University Hospital (G-NUH) Registry, NCT04650529.

Post-PCI Risk Assessment by Inflammation Activity According to Disease Acuity and Time from Procedure.

BACKGROUND: High-sensitivity C-reactive protein (hs-CRP) has been proposed as an indicator of inflammation and cardiovascular risk. However, little is known of the comparative temporal profile of hs-CRP and its relation to outcomes according to the disease acuity. METHODS: We enrolled 4,263 East Asian patients who underwent percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) and stable disease. hs-CRP was measured at baseline and 1 month post-PCI. Major adverse cardiovascular events (MACE: the composite occurrence of death, myocardial infarction, or stroke) and major bleeding were followed up to 4 years. RESULT: The AMI group (n = 2,376; 55.7%) had higher hs-CRPbaseline than the non-AMI group (n = 1,887; 44.3%) (median: 1.5 vs. 1.0 mg/L; p < 0.001), which remained higher at 1 month post-PCI (median: 1.0 vs. 0.9 mg/L; p = 0.001). During 1 month, a high inflammatory-risk phenotype (upper tertile: hs-CRPbaseline ≥ 2.4 mg/L) was associated with a greater MACE in the AMI group (adjusted hazard ratio [HRadj]: 7.66; 95% confidence interval [CI]: 2.29-25.59; p < 0.001), but not in the non-AMI group (HRadj: 0.74; 95% CI: 0.12-4.40; p = 0.736). Between 1 month and 4 years, a high inflammatory-risk phenotype (upper tertile: hs-CRP1 month ≥ 1.6 mg/L) was associated with greater MACE compared to the other phenotype in both the AMI (HRadj: 2.40; 95% CI: 1.73-3.45; p < 0.001) and non-AMI groups (HRadj: 2.67; 95% CI: 1.80-3.94; p < 0.001). CONCLUSION: AMI patients have greater inflammation during the early and late phases than non-AMI patients. Risk phenotype of hs-CRPbaseline correlates with 1-month outcomes only in AMI patients. However, the prognostic implications of this risk phenotype appears similar during the late phase, irrespective of the disease acuity.

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.

Prevalence of adverse events during ticagrelor versus clopidogrel treatment and its association with premature discontinuation of dual antiplatelet therapy in East Asian patients with acute coronary syndrome.

Background: Clinical evidence raises the issues regarding the high risk of adverse events and serious bleeding in East Asian patients receiving standard-dose ticagrelor treatment. We sought to evaluate the association between adverse events and their associations with premature discontinuation of dual antiplatelet therapy (DAPT). Methods: We enrolled East Asian patients presented with acute coronary syndrome who took DAPT with 90-mg ticagrelor (n = 270) or 75-mg clopidogrel (n = 674). During 1-month treatment, antiplatelet effect was evaluated with the VerifyNow P2Y12 assay, and the occurrence of Bleeding Academic Research Consortium (BARC) bleeding and modified Medical Research Council (mMRC) dyspnea was assessed with the dedicated questionnaire. Results: During 1-month follow-up, patients on ticagrelor showed the higher risks of bleeding (any BARC type: 45.6% vs. 23.6%; odds ratio [OR], 2.71 and BARC 1 or 2 type: 45.2% vs. 22.1%; OR, 2.90, respectively) and dyspnea (26.3% vs. 13.6%; OR, 2.25) compared with those on clopidogrel. In a receiver-operating characteristics curve analysis to predict bleeding risk, ticagrelor showed a lower cutoff of low platelet reactivity (LPR) (P2Y12 reaction unit [PRU] ≤ 20) than clopidogrel (PRU ≤ 110). Early occurrence of bleeding episode was significantly associated with LPR phenotype (OR, 2.68), not type of P2Y12 inhibitor. In multivariate analysis, type of P2Y12 inhibitor (ticagrelor vs. clopidogrel: OR, 2.19) and bleeding episode (OR, 2.94) were independent predictors for dyspnea occurrence. During 1-year follow-up, DAPT with ticagrelor showed a higher risk of premature discontinuation compared to DAPT with clopidogrel (27.8% vs. 4.7%; adjusted HR, 8.84), which risk appeared frequent during the first month (14.4%) during DAPT with ticagrelor. Early occurrence of bleeding and dyspnea synergistically increased a risk of DAPT non-adherence, irrespective of type of P2Y12 inhibitor. Conclusion: This analysis is the first evidence to show the different cutoff of low platelet reactivity during the reversible (ticagrelor) versus irreversible P2Y12 inhibitor (clopidogrel). Early occurrence of bleeding and dyspnea is very common during standard-dose ticagrelor treatment in East Asian patients, which show a close association with premature DAPT discontinuation. Clinical trial registration: [https://www.clinicaltrials.gov], identifier[NCT046 50529].

Residual Inflammatory Risk and its Association With Events in East Asian Patients After Coronary Intervention.

Background: East Asian population has a low level of inflammation compared with Western population. The prognostic implication of residual inflammatory risk (RIR) remains uncertain in East Asians. Objectives: This study sought to provide an analysis to estimate early-determined RIR and its association with clinical outcomes in East Asian patients with coronary artery disease (CAD). Methods: In an East Asian registry including patients with CAD undergoing percutaneous coronary intervention (PCI) (n = 4,562), RIR status was determined by measuring high-sensitivity C-reactive protein (hsCRP) serially at admission and at 1-month follow-up. Patients were stratified into 4 groups according to hsCRP criteria (≥2 mg/L): 1) persistent low RIR (lowon admission-low1 month: 51.0%); 2) fortified RIR (lowon admission-high 1 month: 10.3%); 3) attenuated RIR (highon admission-low1 month: 20.5%); and 4) persistent high RIR (highon admission-high1 month: 18.3%). The risks of all-cause death, ischemic events, and major bleeding were evaluated. Results: In our cohort, median levels of hsCRP were significantly decreased over time (1.3 to 0.9 mg/L; P < 0.001). Compared with hsCRP on admission, hsCRP at 1 month showed the greater associations with all-cause death and ischemic event. During clinical follow-up, risks of clinical events were significantly different across the groups (log-rank test, P < 0.001). Compared with other RIR groups, persistent high RIR showed the higher risk for all-cause death (HRadjusted, 1.92; 95% CI: 1.44 to 2.55; P < 0.001), ischemic events (HRadjusted, 1.26; 95% CI: 1.02 to 1.56; P = 0.032), and major bleeding (HRadjusted, 1.98; 95% CI: 1.30 to 2.99; P < 0.001), respectively. Conclusions: Approximately one-fifth of East Asian patients with CAD have persistent high RIR, which shows the close association with occurrence of ischemic and bleeding events. (Gyeongsang National University Hospital Registry [GNUH]; NCT04650529).

Native Aortic Valve Thrombus Complicating Intermittent Occlusion of a Left Main Coronary Artery.

Intermittent left main coronary artery ostium obstruction (LMOO) caused by native aortic valve thrombus (NAVT) is an extremely rare condition. It may therefore be challenging to identify the cause using only coronary angiography, even though the clinical presentation and electrocardiography (ECG) strongly suggest myocardial infarction. We herein report a 53-year-old man with NAVT complicating intermittent occlusion of left main disease in preexisting coronary artery stenosis.

Serum microRNA-185 Levels and Myocardial Injury in Patients with Acute ST-segment Elevation Myocardial Infarction.

Objective Human microRNA-185 (miR-185) has been reported to act as a regulator of fibrosis and angiogenesis in cancer. However, miR-185 has not been investigated in patients with ST-segment elevation myocardial infarction (STEMI). We hypothesized that the changes in miR-185 levels in STEMI patients are related to the processes of myocardial healing and remodeling. Methods Between January 2011 and December 2013, 145 patients with STEMI (65.9±11.6 years old; 41 women) were enrolled. Initial and discharge serum samples collected from 20 patients with STEMI and mixed sera from 8 healthy controls were analyzed by a microarray. A quantitative reverse transcription polymerase chain reaction (RT-qPCR) analysis of miR-185 was performed in all 145 patients. The correlation between the miR-185 levels and the clinical, laboratory, angiographic, and echocardiographic parameters was analyzed. Results The microarray analysis revealed a biphasic pattern in miR-185 levels, with an initial decrease followed by an increase at discharge. The miR-185 levels at discharge were significantly correlated with the troponin-I, CK-MB, and area under the curve of CK-MB levels. There was a positive correlation between the transforming growth factor-ß and miR-185 levels at discharge (ρ=0.242, p=0.026). A high wall motion score index and a low ejection fraction, as measured by echocardiography, and high B-type natriuretic peptide level at one month after STEMI were related to high miR-185 levels. Conclusion Our results showed that elevated miR-185 levels at the late stage of STEMI were related to a large amount of myocardial injury and adverse remodeling.