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: 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.

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: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. Methods: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. Results: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI;additionally, age (65–74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. Conclusions Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.

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.

Background: Early identification of patients with coronavirus disease 2019 (COVID-19) who are at high risk of mortality is of vital importance for appropriate clinical decision making and delivering optimal treatment. We aimed to develop and validate a clinical risk score for predicting mortality at the time of admission of patients hospitalized with COVID-19. Methods: Collaborating with the Korea Centers for Disease Control and Prevention (KCDC), we established a prospective consecutive cohort of 5,628 patients with confirmed COVID-19 infection who were admitted to 120 hospitals in Korea between January 20, 2020, and April 30, 2020. The cohort was randomly divided using a 7:3 ratio into a development (n = 3,940) and validation (n = 1,688) set. Clinical information and complete blood count (CBC) detected at admission were investigated using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-Mortality Score).The discriminative power of the risk model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curves. Results: The incidence of mortality was 4.3% in both the development and validation set.A COVID-Mortality Score consisting of age, sex, body mass index, combined comorbidity, clinical symptoms, and CBC was developed. AUCs of the scoring system were 0.96 (95% confidence interval [CI], 0.85–0.91) and 0.97 (95% CI, 0.84–0.93) in the development and validation set, respectively. If the model was optimized for > 90% sensitivity, accuracies were 81.0% and 80.2% with sensitivities of 91.7% and 86.1% in the development and validation set, respectively. The optimized scoring system has been applied to the public online risk calculator (https://www.diseaseriskscore.com). Conclusion This clinically developed and validated COVID-Mortality Score, using clinical data available at the time of admission, will aid clinicians in predicting in-hospital mortality.

Background: Early identification of patients with coronavirus disease 2019 (COVID-19) who are at high risk of mortality is of vital importance for appropriate clinical decision making and delivering optimal treatment. We aimed to develop and validate a clinical risk score for predicting mortality at the time of admission of patients hospitalized with COVID-19. Methods: Collaborating with the Korea Centers for Disease Control and Prevention (KCDC), we established a prospective consecutive cohort of 5,628 patients with confirmed COVID-19 infection who were admitted to 120 hospitals in Korea between January 20, 2020, and April 30, 2020. The cohort was randomly divided using a 7:3 ratio into a development (n = 3,940) and validation (n = 1,688) set. Clinical information and complete blood count (CBC) detected at admission were investigated using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-Mortality Score).The discriminative power of the risk model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curves. Results: The incidence of mortality was 4.3% in both the development and validation set.A COVID-Mortality Score consisting of age, sex, body mass index, combined comorbidity, clinical symptoms, and CBC was developed. AUCs of the scoring system were 0.96 (95% confidence interval [CI], 0.85–0.91) and 0.97 (95% CI, 0.84–0.93) in the development and validation set, respectively. If the model was optimized for > 90% sensitivity, accuracies were 81.0% and 80.2% with sensitivities of 91.7% and 86.1% in the development and validation set, respectively. The optimized scoring system has been applied to the public online risk calculator (https://www.diseaseriskscore.com). Conclusion This clinically developed and validated COVID-Mortality Score, using clinical data available at the time of admission, will aid clinicians in predicting in-hospital mortality.

OBJECTIVE: We investigated the clinical characteristics of men with testosterone replacement therapy (TRT)-induced hypogonadism and its effect on assisted reproductive technology (ART) in infertile couples.METHODS: This study examined the records of 20 consecutive male patients diagnosed with azoospermia or severe oligozoospermia (<5×10⁶/mL) who visited a single infertility center from January 2008 to July 2018. All patients were treated at a primary clinic for erectile dysfunction or androgen deficiency symptoms combined with low serum testosterone. All men received a phosphodiesterase 5 inhibitor and TRT with testosterone undecanoate (Nebido®) or testosterone enanthate (Jenasteron®). Patients older than 50 years or with a chronic medical disease such as diabetes were excluded.RESULTS: The mean age of patients was 37 years and the mean duration of infertility was 16.3±11.6 months. At the initial presentation, eight patients had azoospermia, nine had cryptozoospermia, and three had severe oligozoospermia. Serum follicle-stimulating hormone levels were below 1.0 mIU/mL in most patients. Three ongoing ART programs with female factor infertility were cancelled due to male spermatogenic dysfunction; two of these men had normal semen parameters in the previous cycle. After withholding TRT, serum hormone levels and sperm concentrations returned to normal range after a median duration of 8 months.CONCLUSION: TRT with high-dose testosterone can cause spermatogenic dysfunction due to suppression of the hypothalamic-pituitary-testicular axis, with adverse effects on infertility treatment programs. TRT is therefore contraindicated for infertile couples attempting to conceive, and the patient's desire for fertility must be considered before initiation of TRT in a hypogonadal man.
Azoospermia ; Cyclic Nucleotide Phosphodiesterases, Type 5 ; Erectile Dysfunction ; Family Characteristics ; Female ; Fertility ; Follicle Stimulating Hormone ; Humans ; Hypogonadism ; Infertility ; Infertility, Male ; Male ; Oligospermia ; Reference Values ; Reproductive Techniques, Assisted ; Semen ; Spermatozoa ; Testosterone

PURPOSE: Sperm cryopreservation before cancer treatment is the most effective method to preserve the fertility of male patients. We present our 21 years experience with sperm cryopreservation for cancer patients, including an examination of semen quality, the current status of cryopreserved sperm, and the rate of sperm use for assisted reproductive technology (ART). MATERIALS AND METHODS: A total of 721 cancer patients at Fertility Center of CHA Gangnam Medical Center successfully performed sperm cryopreservation for fertility preservation from January 1996 to December 2016. Medical chart review was used to analyze patient age, marital status, cancer type, semen volume, sperm counts and motility, length of storage, and current banking status. RESULTS: The major cancers of the 721 patients were leukemia (28.4%), lymphoma (18.3%), testis cancer (10.0%). The mean age at cryopreservation was 27.0 years, and 111 patients (15.4%) performed sperm cryopreservation during or after cancer treatment. The mean sperm concentration was 66.7±66.3 ×106/mL and the mean sperm motility was 33.8%±16.3%. During median follow-up duration of 75 months (range, 1–226 months), 44 patients (6.1%) used their banked sperm at our fertility center for ART and 9 patients (1.2%) transferred their banked sperm to another center. The median duration from cryopreservation to use was 51 months (range, 1–158 months). CONCLUSIONS: Sperm cryopreservation before gonadotoxic treatment is the most reliable method to preserve the fertility of male cancer patients. Sperm cryopreservation should be offered as a standard of care for all men planning cancer therapy.
Cryopreservation ; Fertility Preservation ; Fertility ; Follow-Up Studies ; Humans ; Leukemia ; Lymphoma ; Male ; Marital Status ; Methods ; Reproductive Techniques, Assisted ; Semen ; Semen Analysis ; Semen Preservation ; Sperm Count ; Sperm Motility ; Spermatozoa ; Standard of Care ; Testicular Neoplasms