Background: Coronary artery disease patients undergoing percutaneous coronary intervention (PCI) often exhibit reduced left ventricular ejection fraction (LVEF). However, the impact of LV dysfunction status in conjunction with platelet reactivity on clinical outcomes has not been previously investigated. Methods: From the multicenter PTRG-DES (Platelet function and genoType-Related long-term prognosis in DES-treated patients) consortium, the patients were classified as preserved-EF (PEF: LVEF ≥ 50%) and reduced-EF (REF: LVEF< 5 0%) group by echocardiography. Platelet reactivity was measured using VerifyNow P2Y 12 assay and high platelet reactivity (HPR) was defined as PRU ≥ 252. The major adverse cardiac and cerebrovascular events (MACCEs) were a composite of death, myocardial infarction, stent thrombosis and stroke at 5 years after PCI. Major bleeding was defined as Bleeding Academic Research Consortium bleeding types 3–5. Results: A total of 13,160 patients from PTRG-DES, 9,319 (79.6%) patients with the results of both PRU and LVEF were analyzed. The incidence of MACCE and major bleeding was higher in REF group as compared with PEF group (MACCEs: hazard ratio [HR] 2.17, P < 0.001, 95% confidence interval [CI] 1.85–2.55; major bleeding: HR 1.78, P < 0.001, 95% CI 1.39–2.78).The highest rate of MACCEs was found in patients with REF and HPR, and the difference between the groups was statistically significant (HR 3.14 in REF(+)/HPR(+) vs. PEF(+)/HPR(-) group,P <0.01, 95% CI 2.51–3.91). The frequency of major bleeding was not associated with the HPR in either group. Conclusion LV dysfunction was associated with an increased incidence of MACCEs and major bleeding in patients who underwent PCI. The HPR status further exhibited significant increase of MACCEs in patients with LV dysfunction in a large, real-world registry.Trial Registration: ClinicalTrials.gov Identifier: NCT04734028

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). Conclusions 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.

Purpose: Data are limited on the long-term efficacy and safety of drug-coated balloon (DCB) treatment in comparison to drugeluting stent (DES) for de novo coronary lesions. We investigated the long-term clinical outcomes of DCB treatment in percutaneous coronary intervention (PCI) for de novo coronary lesions. Materials and Methods: A total of 103 patients scheduled for elective PCI for de novo non-small coronary lesions (≥2.5 mm) who were successfully treated with DCB alone were retrospectively compared with 103 propensity-matched patients treated with second-generation DES from the PTRG-DES registry (n=13160). All patients were followed for 5 years. The primary endpoint was major adverse cardiac events [MACE; cardiac death, myocardial infarction, stroke, target lesion thrombosis, target vessel revascularization (TVR), and major bleeding] at 5 years. Results: At 5-year clinical follow-up, Kaplan-Meier estimates of the rate of MACE were significantly lower in the DCB group [2.9% vs. 10.7%; hazard ratio (HR): 0.26; 95% confidence interval (CI): 0.07–0.96; log-rank p=0.027]. There was a significantly lower incidence of TVR in the DCB group (1.0% vs. 7.8%; HR: 0.12; 95% CI: 0.01–0.98; long-rank p=0.015), and there was major bleeding only in the DES group (0.0% vs. 1.9%; log-rank p=0.156). Conclusion At 5-year follow-up, DCB treatment was significantly associated with reduced incidences of MACE and TVR, compared with DES implantation, for de novo coronary lesions.

Given the progressive improvements in antithrombotic strategies, management of cardiovascular disease has become sophisticated/refined. However, the optimal perioperative management of antithrombotic therapy in patients with acute coronary syndrome or who are scheduled for percutaneous coronary intervention remains unclear. Assessments of the thrombotic and hemorrhagic risks are essential to reduce the rates of mortality and major cardiac events. However, the existing guidelines do not mention these topics. This case-based consensus document deals with common clinical scenarios and offers evidence-based guidelines for individualized perioperative management of antithrombotic therapy in the real world.

The prevalence of ischemic heart disease is steadily growing as populations age. Antithrombotic treatment is a key therapeutic modality for the prevention of secondary cerebro-cardiovascular disease. Patients with acute coronary syndrome or who are undergoing percutaneous coronary intervention must be treated with dual antiplatelet therapy for a mandatory period. The optimal perioperative antithrombotic regimen remains debatable; antithrombotics can cause bleeding. Inadequate antithrombotic regimens are associated with perioperative ischemic events, but continuation of therapy may increase the risks of perioperative hemorrhagic complications (including mortality). Many guidelines on the perioperative management of antithrombotic agents have been established by academic societies. However, the existing guidelines do not cover all specialties, nor do they describe the thrombotic and hemorrhagic risks associated with various surgical interventions. Moreover, few practical recommendations on the modification of antithrombotic regimens in patients who require non-deferrable interventions/surgeries or procedures associated with a high risk of hemorrhage have appeared. Therefore, cardiologists, specialists performing invasive procedures, surgeons, dentists, and anesthesiologists have not come to a consensus on optimal perioperative antithrombotic regimens. The Korean Platelet-Thrombosis Research Group presented a positioning paper on perioperative antithrombotic management. We here discuss commonly encountered clinical scenarios and engage in evidence-based discussion to assist individualized, perioperative antithrombotic management in clinical practice.

Purpose: Platelet function test (PFT) results and genotype hold unique prognostic implications in East Asian patients. The aim of the PTRG-DES (Platelet function and genoType-Related long-term proGnosis in Drug-Eluting Stent-treated Patients with coronary artery disease) consortium is to assess the clinical impact thereof on long-term clinical outcomes in Korean patients with coronary artery disease during dual antiplatelet therapy (DAPT) including clopidogrel. Materials and Methods: Searching publications on the PubMed, we reviewed clopidogrel treatment studies with PFT and/or genotype data for potential inclusion in this study. Lead investigators were invited to share PFT/genotype results, patient characteristics, and clinical outcomes to evaluate relationships among them. Results: Nine registries from 32 academic centers participated in the PTRG-DES consortium, contributing individual patient data from 13160 patients who underwent DES implantation between July 2003 and August 2018. The PTRG-PFT cohort was composed of 11714 patients with available VerifyNow assay results. Platelet reactivity levels reached 218±79 P2Y12 reaction units (PRU), and high on-clopidogrel platelet reactivity based on a consensus-recommended cutoff (PRU >208) was observed in 55.9%. The PTRGGenotype cohort consisted of 8163 patients with candidate genotypes related with clopidogrel responsiveness. Of those with cytochrome P450 (CYP) 2C19 genotype, frequencies of carrying one and two loss-of-function allele (s) (*2 or *3) were 47.9% (intermediate metabolizers) and 14.2% (poor metabolizers), respectively. Conclusion The PTRG-DES consortium highlights unique values for on-clopidogrel platelet reactivity and CYP2C19 phenotype that may be important to developing optimal antiplatelet regimens in East Asian patients.

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS: HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534
Blood Platelets ; Echocardiography, Three-Dimensional ; Follow-Up Studies ; Humans ; Korea ; Models, Animal ; Myocardial Infarction ; Myocardium ; Natriuretic Peptide, Brain ; Percutaneous Coronary Intervention ; Random Allocation ; Reperfusion Injury ; Ventricular Remodeling

BACKGROUND AND OBJECTIVES: Impaired recovery from left ventricular (LV) dysfunction is a major prognostic factor after myocardial infarction (MI). Because P2Y12 receptor blockade inhibits myocardial injury, ticagrelor with off-target properties may have myocardial protection over clopidogrel. In animal models, ticagrelor vs. clopidogrel protects myocardium against reperfusion injury and improves remodeling after MI. We aimed to investigate the effect of ticagrelor on sequential myocardial remodeling process after MI. METHODS: High platelet inhibition with ticagrelor to improve LV remodeling in patients with ST-segment elevation MI (HEALING-AMI) is an investigator-initiated, randomized, open-label, assessor-blinded, multi-center trial done at 10 sites in Korea. Patients will be enrolled if they have ST-segment elevation MI (STEMI) treated with primary percutaneous coronary intervention and a planned duration of dual antiplatelet treatment of at least 6 months. Screened patients will be randomly assigned (1:1) using an internet-based randomization with a computer-generated blocking with stratification across study sites to either ticagrelor or clopidogrel treatment. The co-primary primary endpoints are LV remodeling index with three-dimensional echocardiography and the level of N-terminal prohormone B-type natriuretic peptide (NT-proBNP) at 6 months representing post-MI remodeling processes. Changes of LV end-systolic/diastolic volume indices and LV ejection fraction between baseline and 6-month follow-up will be also evaluated. Analysis is per protocol. CONCLUSIONS HEALING-AMI is testing the effect of ticagrelor in reducing adverse LV remodeling following STEMI. Our trial would show the benefit of ticagrelor vs. clopidogrel related to the recovery of post-MI LV dysfunction beyond potent platelet inhibition.TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02224534

BACKGROUND/AIMS: Although a low triiodothyronine (T3) state is closely associated with heart failure (HF), it is uncertain whether total T3 levels on admission is correlated with the clinical outcomes of acute myocardial infarction (AMI). The aim of this study is to investigate the prognostic value of total T3 levels for major adverse cardiovascular and cerebrovascular events (MACCEs) in patients with AMI undergone percutaneous coronary intervention (PCI). METHODS: A total of 765 PCI-treated AMI patients (65.4 ± 12.6 years old, 215 women) between January 2012 and July 2014 were included and 1-year MACCEs were analyzed. We assessed the correlation of total T3 and free thyroxine (fT4) with prevalence of 1-year MACCEs and the predictive values of total T3, fT4, and the ratio of total T3 to fT4 (T3/fT4), especially for HF requiring re-hospitalization. RESULTS: Thirty patients (3.9%) were re-hospitalized within 12 months to control HF symptoms. Total T3 levels were lower in the HF group than in the non-HF group (84.32 ± 21.04 ng/dL vs. 101.20 ± 20.30 ng/dL, p < 0.001). Receiver operating characteristic curve analysis showed the cut-offs of total T3 levels (≤ 85 ng/dL) and T3/fT4 (≤ 60) for HF (area under curve [AUC] = 0.734, p < 0.001; AUC = 0.774, p < 0.001, respectively). In multivariate analysis, lower T3/fT4 was an independent predictor for 1-year HF in PCI-treated AMI patients (odds ratio, 1.035; 95% confidential interval, 1.007 to 1.064; p = 0.015). CONCLUSIONS: Lower levels of total T3 were well correlated with 1-year HF in PCI-treated AMI patients. The T3/fT4 levels can be an additional marker to predict HF.
Area Under Curve ; Heart Failure* ; Heart* ; Humans ; Multivariate Analysis ; Myocardial Infarction* ; Percutaneous Coronary Intervention ; Prevalence ; Prognosis ; ROC Curve ; Thyroxine* ; Triiodothyronine*

BACKGROUND AND OBJECTIVES: After the first acute myocardial infarction (AMI), a considerable proportion of patients are newly diagnosed with diabetes mellitus (DM). However, in AMI, controversy remains regarding the disparity in prognosis between previously diagnosed DM (known-DM) and newly diagnosed DM (new-DM). METHODS: The study included 10,455 patients with AMI (non-DM, 6,236; new-DM, 659; known-DM, 3,560) admitted to one of 15 participating centers in Korea between November 2011 and January 2016 (average follow-up, 523 days). We compared the characteristics and clinical course of patients with known-DM and those with new- or non-DM. RESULTS: Compared to patients with known-DM, those with new-DM or non-DM were younger, more likely to be male, and less likely to have hypertension, dyslipidemia, prior stroke, angina, or myocardial infarction. Compared to patients with new-DM or non-DM (reference), those with known-DM had higher risks of major adverse cardiac events (hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.06–1.35; p=0.004), cardiac death (HR, 1.26; 95% CI, 1.01–1.57; p=0.042), and congestive heart failure (HR, 1.58; 95% CI, 1.20–2.08). Unlike known-DM, new-DM did not increase the risk of cardiac events (including death). CONCLUSIONS: Known-DM was associated with a significantly higher risk of cardiovascular events after AMI, while new-DM had a similar risk of cardiac events as that noted for non-DM. There were different cardiovascular outcomes according to diabetes status in patients with AMI.
Death ; Diabetes Mellitus ; Dyslipidemias ; Follow-Up Studies ; Heart Failure ; Humans ; Hypertension ; Korea ; Male ; Myocardial Infarction ; Prognosis ; Stroke