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.).

Defining Strategies of Modulation of Antiplatelet Therapy in Patients With Coronary Artery Disease: A Consensus Document from the Academic Research Consortium.

Antiplatelet therapy is the mainstay of pharmacologic treatment to prevent thrombotic or ischemic events in patients with coronary artery disease treated with percutaneous coronary intervention and those treated medically for an acute coronary syndrome. The use of antiplatelet therapy comes at the expense of an increased risk of bleeding complications. Defining the optimal intensity of platelet inhibition according to the clinical presentation of atherosclerotic cardiovascular disease and individual patient factors is a clinical challenge. Modulation of antiplatelet therapy is a medical action that is frequently performed to balance the risk of thrombotic or ischemic events and the risk of bleeding. This aim may be achieved by reducing (ie, de-escalation) or increasing (ie, escalation) the intensity of platelet inhibition by changing the type, dose, or number of antiplatelet drugs. Because de-escalation or escalation can be achieved in different ways, with a number of emerging approaches, confusion arises with terminologies that are often used interchangeably. To address this issue, this Academic Research Consortium collaboration provides an overview and definitions of different strategies of antiplatelet therapy modulation for patients with coronary artery disease, including but not limited to those undergoing percutaneous coronary intervention, and consensus statements on standardized definitions.

Prognostic Implications of N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Non-ST-Elevation Myocardial Infarction.

BACKGROUND: Limited data exist regarding the prognostic implications of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients with non-ST-elevation myocardial infarction (NSTEMI) who undergo percutaneous coronary intervention (PCI).Methods and Results: Of 13,104 patients in the nationwide Korea Acute Myocardial Infarction Registry-National Institutes of Health, 3,083 patients with NSTEMI who underwent PCI were included in the present study. The primary endpoint was major adverse cardiovascular events (MACE) at 3 years, a composite of all-cause death, recurrent myocardial infarction, unplanned repeat revascularization, and admission for heart failure. NT-proBNP was measured at the time of initial presentation for the management of NSTEMI, and patients were divided into a low (<700 pg/mL; n=1,813) and high (≥700 pg/mL; n=1,270) NT-proBNP group. The high NT-proBNP group had a significantly higher risk of MACE, driven primarily by a higher risk of cardiac death or admission for heart failure. These results were consistent after confounder adjustment by propensity score matching and inverse probability weighting analysis. CONCLUSIONS: In patients with NSTEMI who underwent PCI, an initial elevated NT-proBNP concentration was associated with higher risk of MACE at 3 years, driven primarily by higher risks of cardiac death or admission for heart failure. These results suggest that the initial NT-proBNP concentration may have a clinically significant prognostic value in NSTEMI patients undergoing PCI.

Association between intensive care unit nursing grade and mortality in patients with cardiogenic shock and its cost-effectiveness.

BACKGROUND: Despite the high workload of cardiac intensive care unit (ICU), there is a paucity of evidence on the association between nurse workforce and mortality in patients with cardiogenic shock (CS). This study aimed to evaluate the prognostic impact of the ICU nursing grade on mortality and cost-effectiveness in CS. METHODS: A nationwide analysis was performed using the K-NHIS database. Patients diagnosed with CS and admitted to the ICU at tertiary hospitals were enrolled. ICU nursing grade was defined according to the bed-to-nurse ratio: grade1 (bed-to-nurse ratio < 0.5), grade2 (0.5 ≤ bed-to-nurse ratio < 0.63), and grade3 (0.63 ≤ bed-to-nurse ratio < 0.77) or above. The primary endpoint was in-hospital mortality. Cost-effective analysis was also performed. RESULTS: Of the 72,950 patients with CS, 27,216 (37.3%) were in ICU nursing grade 1, 29,710 (40.7%) in grade 2, and 16,024 (22.0%) in grade ≥ 3. The adjusted-OR for in-hospital mortality was significantly higher in patients with grade 2 (grade 1 vs. grade 2, 30.6% vs. 37.5%, adjusted-OR 1.14, 95% CI1.09-1.19) and grade ≥ 3 (40.6%) with an adjusted-OR of 1.29 (95% CI 1.23-1.36) than those with grade 1. The incremental cost-effectiveness ratio of grade1 compared with grade 2 and ≥ 3 was $25,047/year and $42,888/year for hospitalization and $5151/year and $5269/year for 1-year follow-up, suggesting that grade 1 was cost-effective. In subgroup analysis, the beneficial effects of the high-intensity nursing grade on mortality were more prominent in patients who received CPR or multiple vasopressors usage. CONCLUSIONS: For patients with CS, ICU grade 1 with a high-intensity nursing staff was associated with reduced mortality and more cost-effectiveness during hospitalization compared to grade 2 and grade ≥ 3, and its beneficial effects were more pronounced in subjects at high risk of CS.

Optimal Antithrombotic Therapy Beyond 1-Year After Coronary Revascularization in Patients With Atrial Fibrillation.

BACKGROUND: Currently, non-vitamin K-antagonist oral anticoagulant (NOAC) monotherapy has been suggested as the optimal antithrombotic therapy for atrial fibrillation (AF) beyond one year after coronary revascularization. The aim of this study was to compare the outcomes between NOAC monotherapy and NOAC plus antiplatelet combination therapy using real-world data. METHODS: Between 2015 and 2020, patients with AF who had received NOACs beyond one year after coronary revascularization were enrolled from Korean national insurance data. We emulated a pragmatic sequence of trials between the NOAC monotherapy and the antiplatelet combination therapy followed by propensity score matching. The primary endpoint was major adverse cardiac and cerebrovascular events (MACCEs), a composite of all-cause death, myocardial infarction, and stroke. RESULTS: Among 206,407 person-trials from 4,465 individuals, we compared 3,275 pairs of the monotherapy and the matched combination therapy. During a median follow-up of 1.24 years, the incidence rate of MACCE was 19.4% and 20.0% per patient-year in the monotherapy group and the antiplatelet combination group, respectively (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.88-1.05; P = 0.422). Compared with the antiplatelet combination group, the monotherapy group had a significantly lower incidence rate of major bleeding, defined as intracranial bleeding or gastrointestinal bleeding requiring hospitalization (2.8% vs. 3.6% per patient-year; HR, 0.78; 95% CI, 0.62-0.97; P = 0.024). CONCLUSION: As an antithrombotic therapy for AF beyond one year after coronary revascularization, NOAC monotherapy was associated with a similar risk of MACCE and a lower risk of major bleeding compared to NOAC plus antiplatelet combination therapy.

Dual antiplatelet therapy duration after percutaneous coronary intervention in high bleeding risk: a meta-analysis of randomized trials.

AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in patients at high bleeding risk (HBR) is still debated. The current study, using the totality of existing evidence, evaluated the impact of an abbreviated DAPT regimen in HBR patients. METHODS AND RESULTS: A systematic review and meta-analysis was performed to search randomized clinical trials comparing abbreviated [i.e. very-short (1 month) or short (3 months)] with standard (≥6 months) DAPT in HBR patients without indication for oral anticoagulation. A total of 11 trials, including 9006 HBR patients, were included. Abbreviated DAPT reduced major or clinically relevant non-major bleeding [risk ratio (RR): 0.76, 95% confidence interval (CI): 0.61-0.94; I2 = 28%], major bleeding (RR: 0.80, 95% CI: 0.64-0.99, I2 = 0%), and cardiovascular mortality (RR: 0.79, 95% CI: 0.65-0.95, I2 = 0%) compared with standard DAPT. No difference in all-cause mortality, major adverse cardiovascular events, myocardial infarction, or stent thrombosis was observed. Results were consistent, irrespective of HBR definition and clinical presentation. CONCLUSION: In HBR patients undergoing PCI, a 1- or 3-month abbreviated DAPT regimen was associated with lower bleeding and cardiovascular mortality, without increasing ischaemic events, compared with a ≥6-month DAPT regimen. STUDY REGISTRATION: PROSPERO registration number CRD42021284004.

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.

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.

Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization: A Cohort Study.

PURPOSE: Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. METHOD: Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10-20 mg or rosuvastatin 5-10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. RESULTS: At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86-1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74-1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. CONCLUSIONS: Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.

Comparison Between Fimasartan Versus Other Angiotensin Receptor Blockers in Patients With Heart Failure After Acute Myocardial Infarction.

BACKGROUNDS: Fimasartan is the most recently developed, potent, and long-acting angiotensin II receptor blocker (ARB). However, data are limited regarding treatment effects of fimasartan in patients with heart failure. METHODS: Between 2010 and 2016, patients who underwent coronary revascularization for myocardial infarction (MI) with heart failure and prescription of ARB at hospital discharge were enrolled from the Korean nationwide medical insurance data. Clinical outcomes were compared between patients receiving fimasartan and those receiving other ARBs (candesartan, valsartan, losartan, telmisartan, olmesartan, and irbesartan). The primary outcome was a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke. RESULTS: Of 2,802 eligible patients, fimasartan was prescribed to 124 patients (4.4%). During a median follow-up of 2.2 years (interquartile range, 1.0-3.9), 613 events of the primary outcome occurred. There was no significant difference in the primary outcome between patients receiving fimasartan and those receiving other ARBs (adjusted hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.46-1.45). Compared with patients receiving other ARBs, those receiving fimasartan had comparable incidence of all-cause death (adjusted HR, 0.70; 95% CI, 0.30-1.63), recurrent MI (adjusted HR, 1.28; 95% CI, 0.49-3.34), hospitalization for heart failure (adjusted HR, 0.70; 95% CI, 0.27-1.84), and stroke (adjusted HR, 0.59; 95% CI, 0.18-1.96). CONCLUSION: In this nationwide cohort, fimasartan, compared with other ARBs, had comparable treatment effects for a composite of all-cause death, recurrent MI, hospitalization for heart failure, and stroke in patients with heart failure after MI.

Sex-Based Outcomes of P2Y12 Inhibitor Monotherapy After Three Months of Dual Antiplatelet Therapy in Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND: In patients undergoing percutaneous coronary intervention (PCI) in the SMART-CHOICE trial, P2Y12 inhibitor monotherapy after three months of dual antiplatelet therapy (DAPT) achieved clinical outcomes comparable to those of 12 months of DAPT. Nonetheless, the effects of sex on these outcomes remain unknown. METHODS: This open-label, non-inferiority, randomized study, conducted in 33 hospitals in South Korea, included 2,993 patients undergoing PCI with drug-eluting stents. Patients were randomly assigned to receive DAPT (aspirin plus a P2Y12 inhibitor) for three months then P2Y12 inhibitor alone for nine months, or DAPT for the entire 12 months. The primary endpoints were major adverse cardiac and cerebrovascular events (a composite of all-cause death, myocardial infarction, or stroke) 12 months after the index procedure. The bleeding endpoints were Bleeding Academic Research Consortium (BARC) bleeding types 2 to 5. RESULTS: Of the patients, 795 (26.6%) were women, who were older and had a higher prevalence of hypertension, diabetes, and dyslipidemia than men. The sexes exhibited comparable primary endpoints (adjusted hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.55-1.55; P = 0.770) and bleeding endpoints (adjusted HR, 1.07; 95% CI, 0.63-1.81; P = 0.811). P2Y12 inhibitor monotherapy vs DAPT was associated with lower risk of BARC type 2 to 5 bleeding in women (adjusted HR, 0.40; 95% CI, 0.16-0.98; P = 0.045) but the difference was not statistically significant when using the Bonferroni correction. The primary endpoints were similar between treatment groups in both sexes. CONCLUSION: In both sexes undergoing PCI, P2Y12 inhibitor monotherapy after three months of DAPT achieved similar risks of the primary endpoints and the bleeding events compared with prolonged DAPT. Therefore, the benefits of early aspirin withdrawal with ongoing P2Y12 inhibitors may be comparable in women and men. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02079194.

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.

Coronary Microcirculatory Dysfunction and Acute Cellular Rejection After Heart Transplantation.

BACKGROUND: Acute cellular rejection is a major determinant of mortality and retransplantation after heart transplantation. We sought to evaluate the prognostic implications of coronary microcirculatory dysfunction assessed by index of microcirculatory resistance (IMR) for the risk of acute cellular rejection after heart transplantation. METHODS: The present study prospectively enrolled 154 heart transplant recipients who underwent scheduled coronary angiography and invasive coronary physiological assessment 1 month after transplantation. IMR is microcirculatory resistance under maximal hyperemia. By measuring hyperemic mean transit time using 3 injections (4 mL each) of room-temperature saline under maximal hyperemia, IMR was calculated as hyperemic distal coronary pressure×hyperemic mean transit time. The primary end point was biopsy-proven acute cellular rejection of grade ≥2R during 2 years of follow-up after transplantation and was compared by using multivariable Cox proportional hazards regression according to IMR. The incremental prognostic value of IMR, in addition to the model with clinical factors, was evaluated by comparison of C-index, net reclassification index, and integrated discrimination index. RESULTS: The mean age of recipients was 51.2±13.1 years (81.2% male), and the cumulative incidence of acute cellular rejection was 19.0% at 2 years. Patients with acute cellular rejection had significantly higher IMR values at 1 month than those without acute cellular rejection (23.1±8.6 versus 16.8±11.1, P=0.002). IMR was significantly associated with the risk of acute cellular rejection (per 5-U increase: adjusted hazard ratio, 1.18 [95% CI, 1.04-1.34], P=0.011) and the optimal cutoff value of IMR to predict acute cellular rejection was 15. Patients with IMR≥15 showed significantly higher risk of acute cellular rejection than those with IMR<15 (34.4% versus 3.8%; adjusted hazard ratio, 15.3 [95% CI 3.6-65.7], P<0.001). Addition of IMR to clinical variables showed significantly higher discriminant and reclassification ability for risk of acute cellular rejection (C-index 0.87 versus 0.74, P<0.001; net reclassification index 1.05, P<0.001; integrated discrimination index 0.20, P<0.001). CONCLUSIONS: Coronary microcirculatory dysfunction assessed by IMR measured early after heart transplantation showed significant association with the risk of acute cellular rejection. In addition to surveillance endomyocardial biopsy, early stratification using IMR could be a clinically useful tool to identify patients at higher risk of future acute cellular rejection after heart transplantation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02798731.

Association Between Preexisting Elevated Left Ventricular Filling Pressure and Clinical Outcomes of Future Acute Myocardial Infarction.

BACKGROUND: Because no data were available regarding the effect of preexisting left ventricular filling pressure (LVFP) on clinical outcomes in patients with acute myocardial infarction (AMI), we evaluated whether preexisting high LVFP can determine outcomes of subsequent AMI events.Methods and Results:Among 399,613 subjects who underwent echocardiography for various reason from August 2004 to June 2019, 231 had experienced subsequent AMI and were stratified according to preexisting LVFP: low LVFP (E/e' ≤14) and high LVFP (E/e' >14). The primary outcome was cardiac death at 30 days and 1 year after AMI. Overall, 19.5% had high LVFP prior to AMI events. Preexisting high LVFP was associated with an increased risk of cardiac death at 30 days (3.8% vs. 11.6%; adjusted hazard ratio (HR) 4.56, 95% confidence interval (CI) 1.20-17.24, P=0.026) and 1 year after AMI (7.9% vs. 35.9%; adjusted HR 4.14, 95% CI 1.79-9.57, P<0.001). Preexisting E/e' as a continuous value was significantly associated with 1-year risk of cardiac death (adjusted HR 1.08, 95% CI 1.02-1.15, P=0.007). Follow-up echocardiography showed that patients with high LVFP did not show improvement in systolic or diastolic function. CONCLUSIONS: Preexisting high LVFP was associated with poor clinical course and 1-year cardiac death after subsequent AMI, as well as no improvement in systolic or diastolic function.

Differential Prognostic Implications of Vasoactive Inotropic Score for Patients With Acute Myocardial Infarction Complicated by Cardiogenic Shock According to Use of Mechanical Circulatory Support.

OBJECTIVES: To identify whether the prognostic implications of Vasoactive Inotropic Score according to use of mechanical circulatory support differ in the treatment of acute myocardial infarction complicated by cardiogenic shock. DESIGN: A multicenter retrospective and prospective observational cohort study. SETTING/PATIENT: The REtrospective and prospective observational Study to investigate Clinical oUtcomes and Efficacy registry includes 1,247 patients with cardiogenic shock from 12 centers in Korea. A total of 836 patients with acute myocardial infarction complicated by cardiogenic shock were finally selected, and the study population was stratified by quartiles of Vasoactive Inotropic Score (< 10, 10-30, 30-90, and > 90) for the present study. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Primary endpoint was in-hospital mortality and secondary endpoint was follow-up mortality. Among the study population, 326 patients (39.0%) received medical treatment alone, 218 (26.1%) received intra-aortic balloon pump, and 292 (34.9%) received extracorporeal membrane oxygenation. In-hospital mortality occurred in 305 patients (36.5%) and was significantly higher in patients with higher Vasoactive Inotropic Score (15.6%, 20.8%, 40.2%, and 67.3%, for < 10, 10-30, 30-90, and > 90; p < 0.001). Vasoactive Inotropic Score showed better ability to predict in-hospital mortality in acute myocardial infarction patients with cardiogenic shock who received medical treatment alone (area under the curve: 0.797; 95% CI, 0.728-0.865) than in those who received intra-aortic balloon pump (area under the curve, 0.704; 95% CI, 0.625-0.783) or extracorporeal membrane oxygenation (area under the curve, 0.644; 95% CI, 0.580-0.709). The best cutoff value of Vasoactive Inotropic Score for the prediction of in-hospital mortality also differed according to the use of mechanical circulatory support (16.5, 40.1, and 84.0 for medical treatment alone, intra-aortic balloon pump, and extracorporeal membrane oxygenation, respectively). There was a significant interaction between Vasoactive Inotropic Score as a continuous value and the use of mechanical circulatory support including intra-aortic balloon pump (interaction-p = 0.006) and extracorporeal membrane oxygenation (interaction-p < 0.001) for all-cause mortality during follow-up. CONCLUSIONS: High Vasoactive Inotropic Score was associated with significantly higher in-hospital and follow-up mortality in patients with acute myocardial infarction complicated by cardiogenic shock. The predictive value of Vasoactive Inotropic Score for mortality was significantly higher in acute myocardial infarction patients with cardiogenic shock treated by medical treatment alone than in those treated by mechanical circulatory support such as intra-aortic balloon pump or extracorporeal membrane oxygenation.

Sex difference in long-term clinical outcomes after percutaneous coronary intervention: A propensity-matched analysis of National Health Insurance data in Republic of Korea.

OBJECTIVE: We investigated the gender difference in the 5-year outcome after percutaneous coronary intervention (PCI) using an unselected population data. BACKGROUND: Sex-specific outcome after percutaneous coronary intervention (PCI) is not consistent among studies. METHODS: A total of 48,783 patients were enrolled from a Korean nationwide cohort of PCI in year 2011. Outcomes adjusted with age and propensity for clinical characteristics were compared. Primary outcome was 5-year cumulative incidence of all-cause death. Nonfatal major adverse clinical event (MACE) consisting of revascularization, shock, or stroke was also assessed. RESULTS: In unadjusted analysis, women were older and had higher frequency of comorbidities including hypertension, hyperlipidemia, and diabetes compared to men (p < .001, all). Women had higher 5-year death risk than men (21.8 vs. 17.3%; hazard ratio [HR] 1.29, 95% confidential interval [CI] 1.23-1.34). In propensity score-matched analysis (N = 28,924), women had lower 5-year death risk (20.2 vs. 26.1%, HR 0.75, 95% CI 0.71-0.78). This lower death risk in women was consistent in subgroup analyses of age, risk factors, and clinical diagnosis including angina or acute myocardial infarction (p < .05, all). CONCLUSIONS: Older age and more common comorbidities in women contributed to the apparent worse outcome after PCI in women. After adjusting these disadvantages, women had better outcome after PCI than men.

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.

Effects of Prolonged Dual Antiplatelet Therapy in ST-Segment Elevation vs. Non-ST-Segment Elevation Myocardial Infarction.

BACKGROUND: The benefits and risks of prolonged dual antiplatelet therapy (DAPT) have not been studied extensively across a broad spectrum of acute coronary syndromes. In this study we investigated whether treatment effects of prolonged DAPT were consistent in patients presenting with ST-segment elevation myocardial infarction (STEMI) vs. non-STEMI (NSTEMI).Methods and Results:As a post hoc analysis of the SMART-DATE trial, effects of ≥12 vs. 6 months DAPT were compared among 1,023 patients presenting with STEMI and 853 NSTEMI patients. The primary outcome was a composite of recurrent myocardial infarction (MI) or stent thrombosis at 18 months after the index procedure. Compared with the 6-month DAPT group, the rate of the composite endpoint was significantly lower in the ≥12-month DAPT group (1.2% vs. 3.8%; hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.12-0.77; P=0.012). The treatment effect of ≥12- vs. 6-month DAPT on the composite endpoint was consistent among NSTEMI patients (0.2% vs. 1.2%, respectively; HR 0.20, 95% CI 0.02-1.70; P=0.140; Pinteraction=0.718). In addition, ≥12-month DAPT increased Bleeding Academic Research Consortium (BARC) Type 2-5 bleeding among both STEMI (4.4% vs. 2.0%; HR 2.18, 95% CI 1.03-4.60; P=0.041) and NSTEMI (5.1% vs. 2.2%; HR 2.37, 95% CI 1.08-5.17; P=0.031; Pinteraction=0.885) patients. CONCLUSIONS: Compared with 6-month DAPT, ≥12-month DAPT reduced recurrent MI or stent thrombosis regardless of the type of MI at presentation.