Prognostic Implication of Platelet Reactivity According to Left Ventricular Systolic Dysfunction Status in Patients Treated With Drug-Eluting Stent Implantation: Analysis of the PTRG-DES Consortium.

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 P2Y12 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.

Drug-coated balloon-based versus drug-eluting stent-only revascularization in patients with diabetes and multivessel coronary artery disease.

BACKGROUND: Data on drug-coated balloon (DCB) treatment in the context of diabetes mellitus (DM) and multivessel coronary artery disease (CAD) are limited. We aimed to investigate the clinical impact of DCB-based revascularization on percutaneous coronary intervention (PCI) in patients with DM and multivessel CAD. METHODS: A total of 254 patients with multivessel disease (104 patients with DM) successfully treated with DCB alone or combined with drug-eluting stent (DES) were retrospectively enrolled (DCB-based group) and compared with 254 propensity-matched patients treated with second-generation DES from the PTRG-DES registry (n = 13,160 patients) (DES-only group). Major adverse cardiovascular events (MACE) comprised cardiac death, myocardial infarction, stroke, stent or target lesion thrombosis, target vessel revascularization, and major bleeding at 2 years. RESULTS: The DCB-based group was associated with a reduced risk of MACE in patients with DM (hazard ratio [HR] 0.19, 95% confidence interval [CI] 0.05-0.68, p = 0.003], but not in those without DM (HR 0.52, 95% CI 0.20-1.38, p = 0.167) at the 2-year follow-up. In patients with DM, the risk of cardiac death was lower in the DCB-based group than the DES-only group, but not in those without DM. In both patients with or without DM, the burdens of DES and small DES (less than 2.5 mm) used were lower in the DCB-based group than in the DES-only group. CONCLUSIONS: In multivessel CAD, the clinical benefit of a DCB-based revascularization strategy appears to be more evident in patients with DM than in those without DM after 2 years of follow-up. (Impact of Drug-Coated Balloon Treatment in De Novo Coronary Lesion; NCT04619277).

Implication of diabetic status on platelet reactivity and clinical outcomes after drug-eluting stent implantation: results from the PTRG-DES consortium.

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 < 0.001) and greater prevalence of HPR compared to non-diabetic patients (38.1% vs. 32.0%, P < 0.001). PRU level and prevalence of HPR were significantly associated with insulin requirement and HbA1c level, as well as diabetic status. DM status and HPR phenotype had a similar prognostic implication, which showed the synergistic clinical impact on MACCE. Association between PRU level and MACCE occurrence seemed higher in diabetic vs. non-diabetic patients. In non-DM patients, HPR phenotype did not significantly increase the risk of MACCE (adjusted hazard ratio [HRadj]: 1.073; 95% confidence interval [CI]: 0.869-1.325; P = 0.511), whereas HPR was an independent determinant for MACCE occurrence among diabetic patients (HRadj: 1.507; 95% CI: 1.193-1.902; P < 0.001). CONCLUSION: The levels of on-clopidogrel platelet reactivity are determined by diabetic status and the severity of DM. In addition, HPR phenotype significantly increases the risk of MACCE only in diabetic patients. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifier: NCT04734028.

Clinical impact of preoperative and postoperative sarcopenia on oncological outcomes in non-metastatic colorectal cancer.

AIM: This study investigated the association between preoperative and postoperative changes in skeletal muscle mass and long-term oncological outcomes in patients with non-metastatic colorectal cancer. METHOD: Patients who underwent surgery for Stages I-III colorectal cancer from January 2014 to December 2015 were included. Skeletal muscle mass was evaluated through preoperative and postoperative abdominopelvic CT scans. A multivariable analysis was conducted to determine the factors affecting disease-free survival rates. RESULTS: A total of 238 patients were analysed. Forty-nine (25.9%) patients had preoperative sarcopenia. Patients with preoperative sarcopenia showed lower 3-year disease-free survival (58.5% vs. 78.4%, P = 0.001). Patients with postoperative sarcopenia also showed significantly lower 3-year disease-free survival compared to postoperative patients without sarcopenia at 6, 12 and 18 months, respectively (53.9% vs. 77.8%; 69.7% vs. 81.8%; 69.1% vs. 87.7%, P = 0.004). In a subgroup analysis, patients with both preoperative and postoperative sarcopenia showed the lowest 3-year disease-free survival rates (50.9%). The incidence of tumour recurrence was higher among the patients who had lost more skeletal muscle mass at 12, 18 and 24 months (-14.3 cm2 /m2 vs. -1.5 cm2 /m2 , P < 0.001; -24.5 cm2 /m2 vs. -1.1 cm2 /m2 , P < 0.001; and -31.6 cm2 /m2 vs. -1.4 cm2 /m2 , P < 0.001, respectively). A multivariable analysis demonstrated that the factors associated with disease-free survival included tumour stage, venous invasion, adjuvant chemotherapy, and preoperative or postoperative sarcopenia. CONCLUSION: Not only preoperative but also postoperative sarcopenic changes adversely affect oncological outcomes following curative resection of colorectal cancer. Careful attention should be given to correcting sarcopenic status from the preoperative to the postoperative period.

Objective recovery time with end-to-side versus side-to-side anastomosis after laparoscopic right hemicolectomy for colon cancer: a randomized controlled trial.

BACKGROUND: Despite reports of the short-term benefits of end-to-side versus side-to-side anastomosis, we are aware of no prospective studies in which these methods were compared. We hypothesized the superiority of end-to-side over side-to-side anastomosis in terms of recovery after laparoscopic right hemicolectomy for colon cancer under an enhanced recovery program. METHODS: From September 2016 to August 2019, 130 patients were randomly allocated to receive end-to-side or side-to-side anastomosis at a single tertiary hospital in Korea. The primary outcome was the cumulative recovery rate seven days after surgery, defined as the percentage of patients who met all four recovery criteria: diet tolerance, no analgesia, safe ambulation, and an afebrile status. Student's t test, the Mann-Whitney U test, the χ2 test, and Fisher's exact test were used to compare variables, as applicable. RESULTS: The cumulative recovery rate at seven days did not differ between patients receiving end-to-side (92.3%, 60/65) or side-to-side anastomosis (92.3%, 60/65; P ≥ 0.999). The end-to-side and side-to-side groups had similar cumulative recovery rates at postoperative days 4, 5, and 6 (end-to-side vs. side-to-side: 41.5% vs 35.4%, P = 0.589; 73.8% vs 63.1%, P = 0.257; and 86.2% vs 81.5%, P = 0.634, respectively). None of the secondary endpoints differed for end-to-side vs. side-to-side anastomosis: the median length of postoperative hospitalization (5 [IQR 5-7] vs. 6 [IQR 5-7] days, respectively, P = 0.376), the 30-day complication rate (16.9% vs. 12.3%, respectively, P = 0.620), the enhanced recovery protocol failure rate (10.8% vs. 7.7%, respectively, P = 0.763), and the 30-day readmission rate (4.6% vs. 3.1%, respectively, P ≥ 0.999). CONCLUSIONS: End-to-side anastomosis was not superior to side-to-side anastomosis in terms of recovery criteria after laparoscopic right hemicolectomy. These findings do not provide evidence for a functional advantage of end-to-side compared to side-to-side anastomosis.

Effects of probiotics on bowel function restoration following ileostomy closure in rectal cancer patients: a randomized controlled trial.

AIM: The aim was to determine the efficacy of probiotics in restoring bowel function following ileostomy reversal in patients with rectal cancer. METHOD: This was a pilot, randomized, double-blind, placebo-controlled trial. The probiotic used in this study, Lactobacillus plantarum CJLP243, was derived from kimchi. Patients were randomly allocated to a probiotic or placebo group and medication was taken once daily from preoperative day 1 to day 21. Primary outcomes were the Memorial Sloan Kettering Cancer Centre Bowel Function Index (MSKCC BFI) instrument and the low anterior resection syndrome score. The secondary outcomes were the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 and CR29 questionnaire responses. RESULTS: Forty patients were enrolled, and 36 patients (probiotics, n = 17; placebo, n = 19) completed the primary outcomes. Total scores for the MSKCC questionnaire (56.2 ± 12.0 vs. 55.0 ± 10.7, P = 0.356) and low anterior resection syndrome scores (33.3 ± 7.6 vs. 36.0 ± 5.3, P = 0.257) were not significantly different between the probiotic and placebo groups, respectively. In the MSKCC BFI, the postoperative dietary scale score at week 1 was significantly higher in the probiotic group (13.1 ± 3.8 vs. 9.0 ± 3.0, P < 0.001). There were no other significant differences between the two groups for any other questionnaire scores. CONCLUSION: There were no significant effects supporting the use of a probiotic for improved bowel function in patients following ileostomy reversal. Nevertheless, the administration of probiotics showed trends toward improvements in some subscale bowel function measures, suggesting further studies may be warranted.

Characteristics and prognosis of patients with cryptogenic stroke and suggestive of patent foramen ovale.

AIMS: The purpose of this study were to identify the usefulness of screening for PFO using agitated saline echocardiography (ASE) and characteristics and prognosis of patients with suggestive of patent foramen ovale (PFO). METHODS: Three hundred three patients (mean age, 53 ± 9 years; 199 [66%] men) admitted with acute stroke or suspicion of stroke were included. Patients were classified into those with and without right-to-left shunt (RLS) according to the ASE results (positive ASE [n = 92] vs. negative ASE [n = 211]). Fifty-one out of ninety-two patients with positive ASE and twenty-one out of two hundred eleven patients with negative ASE underwent TEE with ASE to confirm PFO. RESULTS: Ninety-two were positive for ASE and thirty-six of the fifty-one patients who underwent TEE were confirmed as having PFO. Of the patients with RLS grade 1, 50% were diagnosed with PFO and all patients with RLS grade ≥ 2 were diagnosed with PFO. All patients with negative ASE had no PFO (sensitivity of 100% and specificity of 58%). Patients with positive ASE were younger, had a lower body mass, and a lower prevalence of hypertension. The positive ASE patients had a higher mean S' velocity and better diastolic function. Four of ninety-one patients with positive ASE and thirteen of one hundred seventy-seven showed recurrence of stroke and suspicion of stroke. CONCLUSION: Transthoracic ASE is a good method to screen for PFO. Patients with suggestive of PFO had lower risk factors, less atherosclerosis, and better cardiac performance.

COVID-19 and the heart: what we have learnt so far.

Since the outbreak of COVID-19 or coronavirus disease caused by severe acute respiratory syndrome coronavirus 2 from Wuhan, China, the cardiology fraternity's interest has been drawn towards the pandemic with a high case fatality rate of 10.5% and 6% in patients with heart disease and hypertension, respectively. One of the postulated mechanisms for this high fatality rate is the possible abundance of ACE type 2 receptor in the cardiovascular system that strongly binds with the spike protein of COVID-19 and helps internalise into the cell resulting in acute cardiac injury (ACI). More than 7% of cases with COVID-19 are reported to have this type of ACI. A tenfold rise in mortality has been observed in patients with COVID-19 who experience a rise in high-sensitivity (hs)-troponin. All most half of the patients who died of COVID-19 had a rise in hs-troponin. More than 15% of cases with COVID-19 experienced different types of arrhythmias. All these statistics denote how important cardiovascular pathology is in patients with COVID-19. Controversies of renin-angiotensin-aldosterone system inhibitors usage in patients with COVID-19 and meticulous handling of case with acute coronary syndrome categorically stresses cardiologists to bust the myths hovering around and set a standard guideline to counterfeit the fatality with timely diagnosis and treatment of COVID-19-induced ACI. In this review, we sought to summarise the current evidence of COVID-19-associated cardiac injury and suggest the implications for its proper diagnosis and treatment.

Features of Patients Receiving Extracorporeal Membrane Oxygenation Relative to Cardiogenic Shock Onset: A Single-Centre Experience.

Background and Objectives: Extracorporeal membrane oxygenation (ECMO) can be helpful in patients with cardiogenic shock associated with myocardial infarction, and its early use can improve the patient survival rate. In this study, we report a mortality rate-difference analysis that examined the time and location of shock occurrence. Materials and Methods: We enrolled patients who underwent ECMO due to cardiogenic shock related to myocardial infarction and assigned them to either a pre- or post-admission shock group. The primary outcome was the 1-month mortality rate; a subgroup analysis was conducted to assess the effect of bailout ECMO. Results: Of the 113 patients enrolled, 67 (38 with pre-admission shock, 29 with post-admission shock) were analysed. Asystole was more frequently detected in the pre-admission shock group than in the post-admission group. In both groups, the commonest culprit lesion location was in the left anterior descending artery. Cardiopulmonary resuscitation was performed significantly more frequently and earlier in the pre-admission group. The 1-month mortality rate was significantly lower in the pre-admission group than in the post-admission group. Male sex and ECMO duration (≥6 days) were factors significantly related to the reduced mortality rate in the pre-admission group. In the subgroup analysis, the mortality rate was lower in patients receiving bailout ECMO than in those not receiving it; the difference was not statistically significant. Conclusions: ECMO application resulted in lower short-term mortality rate among patients with out-of-hospital cardiogenic shock onset than with in-hospital shock onset; early cardiopulmonary resuscitation and ECMO might be helpful in select patients.

Surgical outcomes according to the type of monopolar electrocautery device used in laparoscopic surgery for right colon cancer: a comparison of endo-hook versus endo-shears.

BACKGROUND: Although monopolar electrocautery is preferred by many laparoscopic surgeons and is more cost-effective than bipolar or ultrasonic scissors, few studies have compared these outcomes between different monopolar electrocautery devices used in laparoscopic surgery. Therefore, this study compared the surgical outcomes between monopolar endo-hook versus endo-shears during laparoscopic right hemicolectomy for right colon cancer. METHODS: Using a prospective database of patients treated at our institute, we analyzed the surgical outcomes of 358 consecutive patients with right colon cancer who underwent curative laparoscopic surgery with a monopolar endo-hook (n = 164) or endo-shears (n = 194) between March 2009 and March 2017. RESULTS: There were no differences in age, sex, body mass index, American Society of Anesthesiologists' grade, previous operative history, or clinical stage between the endo-hook and endo-shears groups. The estimated blood loss was similar between the endo-hook and endo-shears groups (90.9 ± 60.3 vs. 92.0 ± 89.3 mL; P = 0.893). The number of harvested lymph nodes was greater in the endo-hook group (53.5 ± 20.3 vs. 48.1 ± 18.5; P = 0.008). Hospital stay was shorter in the endo-hook group (6.8 ± 2.2 vs. 7.8 ± 4.8 days; P = 0.013). Although chylous ascites was more frequent in the endo-hook group (21.3% vs. 7.7%, P < 0.001), the postoperative morbidity rate was lower in this group (9.8% vs. 18.0%; P = 0.025). All instances of chylous ascites healed spontaneously without intervention. CONCLUSIONS: This study showed that the use of a monopolar endo-hook during laparoscopic right hemicolectomy might permit more meticulous lymph-node dissection and reduce morbidity compared with the use of monopolar endo-shears. Therefore, we suggest that the outcomes of laparoscopic surgery might be associated with the type of electrocautery device used.

Resting vector volume measured before ileostomy reversal may be a predictor of major fecal incontinence in patients with mid or low rectal cancer: a longitudinal cohort study using a prospective clinical database.

PURPOSE: Despite a high incidence of fecal incontinence following sphincter-preservation surgery (SPS), there are no definitive factors measured before ileostomy reversal that predict fecal incontinence. We investigated whether vector volume anorectal manometry before ileostomy reversal predicts major fecal incontinence following SPS in patients with mid or low rectal cancer. METHODS: This longitudinal prospective cohort study comprised 173 patients who underwent vector volume anorectal manometry before ileostomy reversal. The Fecal Incontinence Severity Index was measured 1 year after the primary SPS and classified as major incontinence (FISI score ≥ 25) or continent/minor incontinence (FISI score < 25). Multivariable logistic regression analysis was used to identify predictors of major incontinence. RESULTS: Ninety-two patients (53.1%) had major incontinence. Although tumor stage, location, and neoadjuvant chemoradiotherapy were comparable, the major incontinence group had lower resting pressure (28.4 vs. 34.3 mmHg, P = 0.027), greater asymmetry at rest (39.1% vs. 34.1%, P = 0.002) and squeezing (34.2% vs. 31.4%, P = 0.046), shorter sphincter length (3.3 vs. 3.7 cm, P = 0.034), and lower resting vector volume (143,601 vs. 278,922 mmHg2 mm, P < 0.001) compared with the continent/minor incontinence group. Resting vector volume was the only independent predictor of major incontinence (odds ratio = 0.675 per 100,000 mmHg2 mm, 95% confidence interval, 0.532-0.823; P = 0.006). CONCLUSIONS: This study revealed that resting vector volume before ileostomy reversal may predict major fecal incontinence. We suggest that the physiology of the anorectum should be discussed with patients before ileostomy reversal in patients at high risk of fecal incontinence.

Pharmacodynamic Comparison of Prasugrel Versus Ticagrelor in Patients With Type 2 Diabetes Mellitus and Coronary Artery Disease: The OPTIMUS (Optimizing Antiplatelet Therapy in Diabetes Mellitus)-4 Study.

BACKGROUND: Patients with diabetes mellitus (DM) are at increased risk of atherothrombotic events, underscoring the importance of effective platelet inhibiting therapies. Prasugrel and ticagrelor reduce thrombotic complications to a greater extent than clopidogrel. Subgroup analyses of pivotal clinical trials testing prasugrel and ticagrelor versus clopidogrel showed DM patients to have benefits that were consistent with the overall trial populations, although the magnitude of the ischemic risk reduction appeared to be enhanced with prasugrel. Whether these findings may be attributed to differences in the pharmacodynamic profiles of these drugs in DM patients remains poorly explored and represented the aim of this study. METHODS: In this prospective, randomized, double-blind, double-dummy, crossover pharmacodynamic study, aspirin-treated DM patients (n=50) with coronary artery disease were randomly assigned to receive prasugrel (60 mg loading dose [LD]/10 mg maintenance dose once daily) or ticagrelor (180 mg LD/90 mg maintenance dose twice daily) for 1 week. Pharmacodynamic assessments were conducted using 4 different assays, including VerifyNow P2Y12, vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate, which allowed us to explore ADP- and non-ADP-induced (arachidonic acid-, collagen-, thrombin receptor-activating, peptide-induced) platelet signaling pathways. The acute (baseline, 30 minutes, and 2 hours post-LD) and maintenance (1 week) effects of therapy were assessed. The primary end point of the study was the comparison of P2Y12 reaction units determined by VerifyNow P2Y12 at 1 week between prasugrel and ticagrelor. RESULTS: ADP- and non-ADP-induced measures of platelet reactivity reduced significantly with both prasugrel and ticagrelor LD and maintenance dose. P2Y12 reaction units defined by VerifyNow were similar between prasugrel and ticagrelor at 30 minutes and 2 hours post-LD. At 1 week, P2Y12 reaction units were significantly lower with ticagrelor than with prasugrel (52 [32-72] versus 83 [63-103]; least-square means difference: -31; 95% confidence interval, -57 to -4; P=0.022; primary end point). Pharmacodynamic assessments measured by vasodilator-stimulated phosphoprotein, light transmittance aggregometry, and Multiplate were similar between prasugrel and ticagrelor at each time point, including at 1 week. Rates of high on-treatment platelet reactivity were similar between groups with all assays at all time points. CONCLUSIONS: In DM patients with coronary artery disease, ticagrelor exerts similar or greater inhibition of ADP-induced platelet reactivity in comparison with prasugrel in the acute and chronic phases of treatment, whereas the inhibition of measures of non-ADP-induced platelet reactivity was not significantly different between the 2 agents. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01852214.

Hospital Outbreaks of Middle East Respiratory Syndrome, Daejeon, South Korea, 2015.

From May through July 2015, a total of 26 cases of Middle East Respiratory Syndrome were reported from 2 hospitals in Daejeon, South Korea, including 1 index case and 25 new cases. We examined the epidemiologic features of these cases and found an estimated median incubation period of 6.1 days (8.8 days in hospital A and 4.6 days in hospital B). The overall attack rate was 3.7% (4.7% in hospital A and 3.0% in hospital B), and the attack rates among inpatients and caregivers in the same ward were 12.3% and 22.5%, respectively. The overall case-fatality rate was 44.0% (28.6% in hospital A and 63.6% in hospital B). The use of cohort quarantine may have played a role in preventing community spread, but additional transmission occurred among members of the hospital cohort quarantined together. Caregivers may have contributed in part to the transmission.

Lower diastolic wall strain is associated with coronary revascularization in patients with stable angina.

BACKGROUND: Left ventricular (LV) diastolic dysfunction occurs earlier in the ischemic cascade than LV systolic dysfunction and electrocardiographic changes. Diastolic wall strain (DWS) has been proposed as a marker of LV diastolic stiffness. Therefore, the objectives of this study were to define the relationship between DWS and coronary revascularization and to evaluate other echocardiographic parameters in patients with stable angina who were undergoing coronary angiography (CAG). METHODS: Four hundred forty patients [mean age: 61 ± 10; 249 (57%) men] undergoing CAG and with normal left ventricular systolic function without regional wall motion abnormalities were enrolled. Among them, 128 (29%) patients underwent revascularization (percutaneous intervention: 117, bypass surgery: 11). All patients underwent echocardiography before CAG and the DWS was defined using posterior wall thickness (PWT) measurements from standard echocardiographic images [DWS = PWT(systole)-PWT(diastole)/PWT(systole)]. RESULTS: Patients who underwent revascularization had a significantly lower DWS than those who did not (0.26 ± 0.08 vs. 0.38 ± 0.09, p < 0.001). Age was comparable between the two groups (61 ± 9 vs. 60 ± 11, p = 0.337), but the proportion of males was significantly higher among patients who underwent revascularization (69 vs. 52%, p = 0.001). The LV ejection fraction was similar but slightly decreased (60.9 ± 5.7 vs. 62.4 ± 6.2%, p = 0.019) and the E/E' ratio was elevated (10.3 ± 4.0 vs. 9.0 ± 3.1, p < 0.001) among patients who underwent revascularization. In multiple regression analysis, lower DWS was an independent predictor of revascularization (cut-off value: 0.34; sensitivity: 89%; AUC: 0.870; SE: 0.025; p < 0.001). CONCLUSION: DWS, a simple parameter that can be calculated from routine 2D echocardiography, is inversely associated with the presence of coronary artery disease and the need for revascularization.

A head-to-head pharmacodynamic comparison of prasugrel vs. ticagrelor after switching from clopidogrel in patients with coronary artery disease: results of a prospective randomized study.

AIMS: Pharmacodynamic (PD) studies comparing prasugrel and ticagrelor have reached inconsistent findings. Therefore, a comprehensive investigation comparing the PD effects of prasugrel vs. ticagrelor after switching from clopidogrel therapy, exploring both loading dose (LD) and maintenance dose (MD) regimens represented the aim of this study. METHODS AND RESULTS: Patients (n = 110) with coronary artery disease were randomized to prasugrel (60 mg LD/10 mg MD q.d.) or ticagrelor (180 mg LD/90 mg MD b.i.d) therapy for 1 week. Pharmacodynamic assessments were conducted using three assays (vasodilator-stimulated phosphoprotein, VerifyNow P2Y12, and light transmittance aggregometry, LTA) at baseline, 30 min, 2, 24 h, and 1 week. The impact of initiating ticagrelor MD 12 vs. 24 h after LD administration was also assessed. Switching clopidogrel-treated patients to an LD of prasugrel or ticagrelor was associated with a reduction in platelet reactivity at 30 min and was sustained at all time points up to 1 week with the MD (P < 0.001 for all assays). Platelet reactivity was similar with prasugrel and ticagrelor with all assays at 30 min, 2 h, and 1 week (P > 0.05 for all time points), with the exception of LTA at 30 min (lower with prasugrel; P = 0.003). At 24 h, platelet reactivity was lower among patients initiating ticagrelor MD after 12 vs. 24 h post-LD. Rates of high platelet reactivity (HPR) were markedly reduced and similar between groups. CONCLUSION: Prasugrel and ticagrelor exert similar levels of P2Y12 inhibition achieving more potent PD effects and reduced HPR rates compared with clopidogrel which are reached promptly following LD and sustained with MD. CLINICALTRIALSGOV IDENTIFIER: NCT01852175.

Percutaneous coronary intervention and atrial fibrillation: the triple therapy dilemma.

Atrial fibrillation (AF) represents the most common cardiac arrhythmia and chronic oral anticoagulation (OAC) is the cornerstone therapy to prevent cerebrovascular events among those having high thromboembolic risk. However, 20-30% of patients with AF have co-existing coronary artery disease (CAD). Importantly, since the prevalence of both AF and CAD increase with age, management of these patients has become an emerging clinical problem with the ever growing elderly population. In particular, many of these patients may develop an acute coronary syndrome (ACS) or require percutaneous coronary intervention (PCI), leading to the concomitant use of dual antiplatelet therapy (DAPT) including aspirin and a P2Y12 receptor inhibitor in addition to OAC, also known as triple antithrombotic therapy (TAT). However, TAT comes at the expense of an increased risk of bleeding complications. This viewpoint focuses on the current evidence of treatment, areas of unmet needs and future perspectives in the management of these high-risk patients.

Role of thromboelastography and rapid thromboelastography to assess the pharmacodynamic effects of vitamin K antagonists.

Thromboelastography (TEG) measures the effects of antithrombotic agents by assessing global functional clotting status by evaluating the viscoelastic properties of in vitro clot formation. Recently, rapid TEG (r-TEG), which uses tissue factor in addition to standard kaolin to accelerate activation of the clotting cascade, has been proposed to obtain more immediate results. The correlation between results of TEG or r-TEG with international normalized ratio (INR) in patients on vitamin K antagonist (VKA) therapy has not been explored and represents the aim of this study. Patients on chronic therapy with VKAs (n = 100) were included in an observational prospective pharmacodynamic study. The correlation between TEG parameters, in particular markers of thrombus generation [Reaction time (R), maximum rate of thrombus generation (MRTG), and time to maximum rate of thrombus generation (TMRTG)], and INR values as well as the concordance between these parameters and therapeutic INR ranges were evaluated. In addition, in a subgroup of subjects (n = 17), the correlation of r-TEG parameters with TEG parameters and INR values was also assessed. No correlation was found between INR and TEG parameters of thrombus generation, in particular between INR and R (r = 0.189, p = 0.06), MRTG (r = -0.027, p = 0.79), and TMRTG (r = 0.188, p = 0.06). Further, no concordance was found between these parameters and recommended INR ranges. Significant Spearman correlations were found between INR and activated clotting time (rS = 0.546, p < 0.001), r-R (rS = 0.572, p = 0.017), and r-TMRTG (rS = 0.510, p = 0.037), but not r-MRTG (rS = 0.131, p = 0.617). Results were obtained in 24 ± 6 versus 12 ± 4 min with TEG and r-TEG, respectively (p < 0.001). In patients on chronic VKA therapy, TEG is not a useful tool to evaluate VKA anticoagulant effect, compared with standard INR measurements. However, r-TEG parameters of thrombus generation correlate with INR levels, suggesting a possible role of this assay for measuring more expeditiously anticoagulant treatment effects.

High platelet reactivity strongly predicts early stent thrombosis in patients with drug-eluting stent implantation.

Stent thrombosis (ST) is a fatal complication after percutaneous coronary intervention (PCI). The association between P2Y12 reaction unit (PRU) level and stent thrombosis occurrence remains unclear. Based on the multicenter, observational PTRG-DES (Platelet function and genoType-Related long-term proGnosis in DES-treated patients) registry of patients with drug-eluting stents (DES) implantation, a total of 11,714 patients with PRU values were analyzed. We sought to identify the predictors of early stent thrombosis (EST) and compared the primary outcome, a composite of cardiac death, myocardial infarction, and revascularization, between EST and non-EST groups. EST, defined as definite ST within 1 month after index PCI, occurred in 51 patients. PRU values were significantly higher in the EST group (263.5 ± 70.8 vs. 217.5 ± 78.7, p < 0.001). In multivariable analysis, PRU ≥ 252 (OR, 5.10; 95% CI 1.58-16.46; p = 0.006) and aspirin reaction unit ≥ 414 (OR 4.85; 95% CI 1.07-21.97; p = 0.040) were independent predictors of EST. The cumulative incidence of primary composite outcome at one year was significantly higher in the EST group (38.2% vs. 3.9%, Log-rank p < 0.001). In patients treated with clopidogrel after successful DES implantation, EST was associated with higher platelet reactivities, and a greater risk of cardiovascular events.Trial Registration: clinicaltrials.gov Identifier: NCT04734028.

Prognostic Implication of Platelet Reactivity According to Procedural Complexity After PCI: Subanalysis of PTRG-DES Consortium.

Background: Complex percutaneous coronary intervention (C-PCI) and high platelet reactivity (HPR) have been proposed as representative risk factors for the high ischemic phenotype. Uncertainty remains regarding the relative prognostic importance of these factors. Objectives: This study aimed to investigate the prognostic implication of HPR according to procedural complexity. Methods: Patients treated with drug-eluting stent implantation (PTRG-PFT cohort; N = 11,714) were classified according to procedural complexity. HPR criteria were determined using VerifyNow (≥252 P2Y12 reaction units). The major adverse cardiac and cerebrovascular events (MACCE) (the composite of all-cause death, myocardial infarction, definite stent thrombosis, or stroke) and major bleeding were assessed for up to 3 years. Results: C-PCI was performed in 3,152 patients (26.9%). C-PCI significantly increased the risk of MACCE (HRadjusted: 1.21; 95% CI: 1.01-1.44; P = 0.035), driven by a higher rate of all-cause death (HRadjusted: 1.45; 95% CI: 1.15-1.83; P = 0.002), although it did not increase the risk of major bleeding. Irrespective of procedural complexity, the HPR phenotype was significantly associated with MACCE (Pinteraction = 0.731) and all-cause mortality (Pinteraction = 0.978), in which the prognostic implication appeared prominent within 1 year. The HPR phenotype did not show a significant interaction with any type of C-PCI. In addition, the number of complexity features per procedure did not proportionally increase the risk of MACCE. Conclusions: C-PCI was significantly associated with 3-year risk of MACCE and all-cause death. The HPR phenotype appears to have a similar prognostic implication irrespective of the type and extent of procedural complexity. (Platelet Function and Genotype-Related Long-Term Prognosis in DES-Treated Patients [PTRG-DES]; NCT04734028).

Association of Age- and Body Mass Index-Stratified High On-Treatment Platelet Reactivity With Coronary Intervention Outcomes in East Asian Patients.

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 (<67 years of age or ≥67 years of age) and BMI (≤22.6 kg/m2 or >22.6 kg/m2). Patients <67 years of age with HPR had increases in both MACCEs (adjusted hazard ratio [HR], 1.436 [95% CI, 1.106-1.867]; P=0.007) and major bleeding (adjusted HR, 1.584 [95% CI, 1.095-2.290]; P=0.015) compared with the those with non-HPR, respectively. In patients ≥67 years of age with HPR, there were no differences in MACCEs, but there was a decrease in major bleeding (adjusted HR, 0.721 [95% CI, 0.542-0.959]; P=0.024). Meanwhile, patients with HPR with BMI >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.