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Background and objectivesThe optimal timing for complete revascularization (CR) in patients with acute myocardial infarction (AMI) and multivessel disease (MVD) remain uncertain.MethodsThis post-hoc analysis of the FRAME-AMI trial included AMI patients with MVD (n = 549). They were classified into immediate (n = 329) and staged CR (n = 220) groups. All percutaneous coronary interventions were performed during inex hospitalization. The primary endpoint was a composite of all-cause death, acute myocardial infarction, and repeated revascularization. Secondary endpoints included each component of the primary endpoint. Additional comparisons for the outcomes in ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) were also performed.ResultsThe incidence of the primary endpoint was not significantly different in any of the AMI patients [12.7% [immediate CR] vs. 17.4% [staged CR], p = 0.905, adjusted hazard ratio [HR] of staged CR = 0.81, 95% confidence interval = 0.43–1.53, p = 0.528]. Other secondary endpoints were also not significantly different. Analyses of STEMI and Neither the primary or secondary endpoints of NSTEMI patients were significantly different.ConclusionsIn this post-hoc analysis of the FRAME-AMI trial, no significant difference in clinical outcomes was observed between the immediate and staged CR strategies for AMI with MVD and the subgroups, such as STEMI or NSTEMI. However, the results should be interpreted carefully because of the many limitations, including a limited sample size and a lack of statistical power. Trial Registration: FRAME-AMI clinicaltrials.gov, identifier (NCT02715518).

Aims: Calcium channel blockers (CCBs) are frequently co-administered with clopidogrel in cardiovascular disease. Although an inhibitory drug interaction exists between them, comprehensive large-scale studies for its validation are lacking. We investigated interactions between CCBs and clopidogrel using a large-scale national registry of patients who underwent percutaneous coronary intervention (PCI). Methods and Results: The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test consortium investigates the association between platelet function test and long-term prognosis during dual antiplatelet therapy including clopidogrel in patients using drug-eluting stents. We compared the ex vivo platelet reactivity using the VerifyNow P2Y12 test and clinical outcomes between CCB users and non-users. Between 2003 and 2018, 11 714 patients were enrolled and categorized into two groups according to CCB usage. A composite endpoint encompassing all-cause mortality, myocardial infarction, stent thrombosis, or stroke was defined as a major adverse cardiac and cerebrovascular event (MACCE). During the 5-year follow-up period, no significant differences were observed in P2Y12 reaction units (215.8 ± 84.7 vs 218.4 ± 76.7, P = .156), MACCEs, major bleeding, or high platelet reactivity rates, even after adjusting for propensity score matching (PSM) and inverse probability of treatment weighting (IPTW). When limited to the high platelet reactivity cohort (≥252 PRU), the results remained consistent for MACCE [PSM-adjusted, HR: 0.923 (0.644-1.323), P -value .663; IPTW-adjusted, HR: 1.300 (0.822-2.056), P -value .262]. Conclusions: CCB and clopidogrel co-administration does not appear to significantly impact clopidogrel responsiveness or clinical outcomes. Despite these promising results, further investigation may be warranted. Clinical trial registration: Platelet Function and genoType-Related Long-term progGosis in DES-treated Patients: A Consortium From Multi-centered Registries [PTRG-DES]; NCT04734028

BackgroundLeft ventricular ejection fraction (LVEF) is a crucial prognostic indicator of acute myocardial infarction (AMI). However, there is a lack of studies on the clinical characteristics and prognosis of patients with mildly reduced ejection fraction (EF) after AMI.MethodsWe categorized 6,553 patients with AMI from the Korea Acute Myocardial Infarction Registry-National Institutes of Health (KAMIR-NIH) between November 2011 and December 2015 into three groups based on their EF, as assessed by echocardiography during index hospitalization: reduced EF (LVEF ≤40%), mildly reduced EF (LVEF 41%–49%), and preserved EF (LVEF ≥50%). The primary outcome was all-cause death within 2 years. The secondary outcomes included myocardial infarction (MI), revascularization, and patient-oriented composite endpoint (POCE), which was defined as a composite of all-cause death, any MI, or revascularization.ResultsOf the total 6,553 patients, 884 (13.5%) were classified into the reduced EF group, 1,749 (26.7%) into the mildly reduced EF group, and 3,920 (59.8%) into the preserved EF group. Patients with mildly reduced EF exhibited intermediate mortality (reduced EF, 24.7%; mildly reduced EF, 8.3%; preserved EF, 4.6%; p

Background Carriers of CYP2C19 loss‐of‐function alleles have increased adverse events after percutaneous coronary intervention, but limited data are available for older patients. We aimed to evaluate the prognostic impact of CYP2C19 genotypes on clinical outcomes in older patients after percutaneous coronary intervention. Methods and Results The study included 1201 older patients (aged ≥75 years) who underwent percutaneous coronary intervention and received clopidogrel‐based dual antiplatelet therapy in South Korea. Patients were grouped on the basis of CYP2C19 genotypes. The primary outcome was 3‐year major adverse cardiac events, defined as a composite of cardiac death, myocardial infarction, and stent thrombosis. Older patients were grouped into 3 groups: normal metabolizer (36.6%), intermediate metabolizer (48.1%), and poor metabolizer (15.2%). The occurrence of the primary outcome was significantly different among the groups (3.1, 7.0, and 6.2% in the normal metabolizer, intermediate metabolizer, and poor metabolizer groups, respectively; P=0.02). The incidence rate of all‐cause death at 3 years was greater in the intermediate metabolizer and poor metabolizer groups (8.1% and 9.2%, respectively) compared with that in the normal metabolizer group (3.5%, P=0.03) without significant differences in major bleeding. In the multivariable analysis, the intermediate metabolizer and poor metabolizer groups were independent predictors of 3‐year clinical outcomes. Conclusions In older patients, the presence of any CYP2C19 loss‐of‐function allele was found to be predictive of a higher incidence of major adverse cardiac events within 3 years following percutaneous coronary intervention. This finding suggests a need for further investigation into an optimal antiplatelet strategy for older patients. Registration URL: https://clinicaltrials.gov. Identifier: NCT04734028.

Background Although age and body mass index (BMI) significantly affect platelet reactivity units and clinical outcomes after percutaneous coronary intervention, there are limited data on the relationship between high on‐treatment platelet reactivity (HPR) and clinical outcomes on age and BMI differences. Thus, we investigated the association of HPR with clinical outcomes according to age and BMI. Methods and Results The study analyzed 11 714 patients who underwent platelet function tests after percutaneous coronary intervention. The primary end point was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), whereas the secondary end point was major bleeding. HPR was defined as platelet reactivity units ≥252. Patients were categorized by age (22.6 kg/m2). Patients 22.6 kg/m2 had increases in MACCEs (adjusted HR, 1.387 [95% CI, 1.140–1.688]; P=0.001). No differences were shown in major bleeding. Conclusions HPR was linked to an increase in MACCEs or a decrease in major bleeding in patients after percutaneous coronary intervention, depending on age and BMI. This study is the first to observe that clinical outcomes in patients with HPR after percutaneous coronary intervention may vary based on age and BMI. Because the study is observational, the results should be viewed as hypothesis generating and emphasize the need for randomized clinical trials.

Abstract Background Diabetes mellitus (DM) is associated with thrombogenicity, clinically manifested with atherothrombotic events after percutaneous cutaneous intervention (PCI). This study aimed to investigate association between DM status and platelet reactivity, and their prognostic implication in PCI-treated patients. Methods The Platelet function and genoType-Related long-term Prognosis-Platelet Function Test (PTRG-PFT) cohort was established to determine the linkage of platelet function test (PFT) with long-term prognosis during dual antiplatelet therapy including clopidogrel in patients treated with drug-eluting stent (DES). We assessed platelet reactivity using VerifyNow and ‘high platelet reactivity (HPR)’ was defined as ≥ 252 P2Y12 reaction unit (PRU). Major adverse cardiac and cerebrovascular event (MACCE) was a composite of all-cause death, myocardial infarction, stent thrombosis or stroke. Results Between July 2003 and Aug 2018, DES-treated patients with available PFT were enrolled (n = 11,714). Diabetic patients demonstrated significant higher levels of platelet reactivity (DM vs. non-DM: 225.7 ± 77.5 vs. 213.6 ± 79.1 PRU, P

Background Although high platelet reactivity (HPR) on clopidogrel is associated with higher ischemic events and lower bleeding events in patients who have undergone percutaneous coronary intervention with drug‐eluting stents, the differential risk of HPR in East Asian women versus men is unknown. Methods and Results We compared 11 714 patients enrolled in the PTRG‐DES (Platelet Function and Genotype‐Related Long‐Term Prognosis in Drug‐Eluting Stent–Treated Patients With Coronary Artery Disease) Consortium according to sex and the presence/absence of HPR on clopidogrel (defined as ≥252 P2Y12 reactivity units). The primary study end point was major adverse cardiac and cerebrovascular events (MACCEs; comprising all‐cause mortality, myocardial infarction, cerebrovascular accident, and stent thrombosis). HPR was more common in women (46.7%) than in men (28.1%). In propensity‐adjusted models, HPR was an independent predictor of MACCEs (men with HPR: hazard ratio [HR], 1.60 [95% CI, 1.20–2.12]; women with HPR: HR, 0.99 [95% CI, 0.69–1.42]) and all‐cause mortality (men with HPR: HR, 1.61 [95% CI, 1.07–2.44]; women with HPR: HR, 0.92 [95% CI, 0.57–1.50]) in men, although those associations were insignificant among women. In addition, a significant interaction between sex was noted in the associations between HPR and MACCE (Pinteraction=0.013) or all‐cause mortality (Pinteraction=0.025). Conclusions In this study, HPR was a differential risk factor for 1‐year MACCEs and all‐cause mortality in women and men. And it was an independent predictor of 1‐year MACCEs and all‐cause mortality in men but not in women. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04734028. Registered July 9, 2003, https://clinicaltrials.gov/ct2/show/NCT04734028

BackgroundThe role of high-flow arteriovenous fistula (AVF) in cardiovascular morbidity in hemodialysis (HD) patients is very likely under-recognized. We assessed the relationship between high access flow (Qa) and myocardial fibrosis in HD patients.MethodsMyocardial fibrosis was assessed by native T1 relaxation times on non-contrast cardiac magnetic resonance imaging and a potential marker of fibrosis. Serum levels of galectin-3, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and monocyte chemoattractant protein 1 (MCP-1) were measured in 101 HD patients who underwent regular monitoring of AVF Qa. A high-flow AVF was defined as a Qa >2 L/min.ResultsHemodialysis patients showed significantly higher galectin-3 value and increased T1 relaxation time compared to healthy volunteers, suggesting increased myocardial fibrosis in uremic cardiomyopathy. In HD patients, 20 (19.8%) had a Qa > 2L/min, and they had significantly higher cardiac output, cardiac index, left ventricular mass, and increased T1 times than those with a Qa ≤ 2 L/min. Also, serum galectin-3 and NT-proBNP levels were much higher in the high Qa group, indicating a close relationship between the high Qa, increased myocardial fibrosis, and the risk of heart failure (HF) in HD patients. It is interesting that a higher AVF Qa for myocardial fibrosis was independent of several traditional cardiovascular risk factors as well as serum levels of NT-proBNP and MCP-1.ConclusionsA supra-physiologically high Qa can be related to myocardial fibrosis and increased risk of HF in HD patients. Regular Qa monitoring could allow early detection of a high-flow AVF that could arise cardiac complications.

Background Although antiplatelet therapy (APT) has been recommended to balance ischemic‐bleeding risks, it has been left to an individualized decision‐making based on physicians' perspectives before non‐cardiac surgery. The study aimed to assess the advantages of a consensus among physicians, surgeons, and anesthesiologists on continuation and regimen of preoperative APT in patients with coronary drug‐eluting stents. Methods and Results A total of 3582 adult patients undergoing non‐cardiac surgery after percutaneous coronary intervention with second‐generation stents was retrospectively included from a multicenter cohort. Physicians determined whether APT should be continued or discontinued for a recommended period before non‐cardiac surgery. There were 3103 patients who complied with a consensus decision. Arbitrary APT, not based on a consensus decision, was associated with urgent surgery, high bleeding risk of surgery, female sex, and dual APT at the time of preoperative evaluation. Arbitrary APT independently increased the net clinical adverse event (adjusted odds ratio [ORadj], 1.98; 95% CI, 1.98–3.11), major adverse cardiac event (ORadj, 3.11; 95% CI, 1.31–7.34), and major bleeding (ORadj, 2.34; 95% CI, 1.45–3.76) risks. The association was consistently noted, irrespective of the surgical risks, recommendations, and practice on discontinuation of APT. Conclusions Most patients were treated in agreement with a consensus decision about preoperative APT based on a referral system among physicians, surgeons, and anesthesiologists. The risk of perioperative adverse events increased if complying with a consensus decision was failed. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03908463.

Background Continuing antiplatelet therapy (APT) has been generally recommended during noncardiac surgery, but it is uncertain if preoperative discontinuation of APT has been avoided or harmful in patients with second‐generation drug‐eluting coronary stents. Methods and Results Patients undergoing noncardiac surgery after second‐generation drug‐eluting coronary stent implantation were assessed in a multicenter cohort in Korea. Net adverse clinical events within 30 days postoperatively, defined as all‐cause death, major adverse cardiac events, and major bleeding, were evaluated. Of 3582 eligible patients, 49% patients discontinued APT during noncardiac surgery. The incidence of net adverse clinical events was comparable between patients with continuation versus discontinuation (4.1% versus 3.4%; P=0.257) of APT during noncardiac surgery. Perioperative discontinuation of APT did not impact on net adverse clinical events (adjusted hazard ratio [HR], 1.00; 95% CI, 0.69–1.44; P=0.995). In subgroup analysis, patients undergoing intra‐abdominal surgery were exposed to less risk of major bleeding by discontinuing APT (adjusted HR, 0.26; 95% CI, 0.08–0.91; P=0.035). Prolonged discontinuation of APT for ≥9 days was associated with higher risk of a major adverse cardiac event compared with continuing APT (adjusted HR, 3.38; 95% CI, 1.36–8.38; P=0.009). Conclusions APT was discontinued preoperatively in almost half of patients with second‐generation drug‐eluting coronary stents. Our explorative analysis showed that there was no significant impact of discontinuing APT on the risk of perioperative adverse events except that discontinuing APT may be associated with decreased hemorrhagic risk in patients undergoing intra‐abdominal surgery. Registration URL: https://www.clini​caltr​ials.gov; Unique identifier: NCT03908463.

Abstract Background B-type natriuretic peptide (BNP) has prognostic significance in heart failure (HF), and reductions in BNP may predict clinical improvement. However, there are limited data regarding the prognostic value of BNP during short-term follow-up. The aim of this study was to evaluate the relationship between short-term follow-up BNP and mortality after discharge in patients with HF. Methods We analyzed 427 patients hospitalized with HF from the Wonju Severance Christian Hospital Heart Failure Registry from April 2011 to December 2013, with a planned follow-up period through February 2016. Of the 427 patients, 240 (mean age, 75 years; 102 males, 42.5%) had BNP measured on admission and within the short-term follow-up period (3 months). We compared all-cause mortality during the clinical follow-up period (median length of follow-up, 709.5 days) according to the median value of BNP on admission (as a baseline value) and over a short-term follow-up period after discharge. Results Median BNP at admission was 816.5 pg/ml, and median follow-up BNP was 369.7 pg/ml. Multivariate analysis revealed a positive association between risk of death and high BNP. High BNP during follow-up was significantly associated with a greater risk of all-cause mortality compared to low BNP (P

BackgroundWe hypothesized that nebivolol, a β‐blocker with nitric oxide–mediated activity, compared with atenolol, a β‐blocker without such activity, would decrease oxidative stress and improve the effects of endothelial dysfunction and wall shear stress (WSS), thereby reducing atherosclerosis progression and vulnerability in patients with nonobstructive coronary artery disease. Methods and ResultsIn this pilot double‐blinded randomized controlled trial, 24 patients treated for 1 year with nebivolol 10 mg versus atenolol 100 mg plus standard medical therapy underwent baseline and follow‐up coronary angiography with assessments of inflammatory and oxidative stress biomarkers, microvascular function, endothelial function, and virtual histology intravascular ultrasound. WSS was calculated from computational fluid dynamics. Virtual histology intravascular ultrasound segments were assessed for vessel volumetrics and remodeling. There was a trend toward more low‐WSS segments in the nebivolol cohort (P=0.06). Low‐WSS regions were associated with greater plaque progression (P