Inverted nucleation for photoinduced nonequilibrium melting.

Ultrafast photoinduced melting provides an essential platform for studying nonequilibrium phase transitions by linking the kinetics of electron dynamics to ionic motions. Knowledge of dynamic balance in their energetics is essential to understanding how the ionic reaction is influenced by femtosecond photoexcited electrons with notable time lag depending on reaction mechanisms. Here, by directly imaging fluctuating density distributions and evaluating the ionic pressure and Gibbs free energy from two-temperature molecular dynamics that verified experimental results, we uncovered that transient ionic pressure, triggered by photoexcited electrons, controls the overall melting kinetics. In particular, ultrafast nonequilibrium melting can be described by the reverse nucleation process with voids as nucleation seeds. The strongly driven solid-to-liquid transition of metallic gold is successfully explained by void nucleation facilitated by photoexcited electron-initiated ionic pressure, establishing a solid knowledge base for understanding ultrafast nonequilibrium kinetics.

Development of the multiplex imaging chamber at PAL-XFEL.

Various X-ray techniques are employed to investigate specimens in diverse fields. Generally, scattering and absorption/emission processes occur due to the interaction of X-rays with matter. The output signals from these processes contain structural information and the electronic structure of specimens, respectively. The combination of complementary X-ray techniques improves the understanding of complex systems holistically. In this context, we introduce a multiplex imaging instrument that can collect small-/wide-angle X-ray diffraction and X-ray emission spectra simultaneously to investigate morphological information with nanoscale resolution, crystal arrangement at the atomic scale and the electronic structure of specimens.

Distal Radial Access for Coronary Procedures in a Large Prospective Multicenter Registry: The KODRA Trial.

BACKGROUND: Distal radial access (DRA) as an alternative access route lacks evidence, despite its recent reputation. OBJECTIVES: The aim of this study was to evaluate the safety and feasibility of DRA on the basis of daily practice. METHODS: The KODRA (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach) trial was a prospective multicenter registry conducted at 14 hospitals between September 2019 and September 2021. The primary endpoints were the success rates of coronary angiography (CAG) and percutaneous coronary intervention (PCI). The secondary endpoints included successful distal radial artery puncture, access-site crossover, access site-related complications, bleeding events, and predictors of puncture failure. RESULTS: A total of 4,977 among 5,712 screened patients were recruited after the exclusion of 735 patients. The primary endpoints, the success rates of CAG and PCI via DRA, were 100% and 98.8%, respectively, among successful punctures of the distal radial artery (94.4%). Access-site crossover occurred in 333 patients (6.7%). The rates of distal radial artery occlusion and radial artery occlusion by palpation were 0.8% (36 of 4,340) and 0.8% (33 of 4,340) at 1-month follow-up. DRA-related bleeding events were observed in 3.3% of patients, without serious hematoma. Multilevel logistic regression analysis identified weak pulse (OR: 9.994; 95% CI: 7.252-13.774) and DRA experience <100 cases (OR: 2.187; 95% CI: 1.383-3.456) as predictors of puncture failure. CONCLUSIONS: In this large-scale prospective multicenter registry, DRA demonstrated high success rates of CAG and PCI, with a high rate of puncture success but low rates of distal radial artery occlusion, radial artery occlusion, bleeding events, and procedure-related complications. Weak pulse and DRA experience <100 cases were predictors of puncture failure. (Korean Prospective Registry for Evaluating the Safety and Efficacy of Distal Radial Approach [KODRA]; NCT04080700).

Nanoscale Three-Dimensional Network Structure of a Mesoporous Particle Unveiled via Adaptive Multidistance Coherent X-ray Tomography.

Mesoporous nanoparticles provide rich platforms to devise functional materials by customizing the three-dimensional (3D) structures of nanopores. With the pore network as a key tuning parameter, the noninvasive and quantitative characterization of these 3D structures is crucial for the rational design of functional materials. This has prompted researchers to develop versatile nanoprobes with a high penetration power to inspect various specimens sized a few micrometers at nanoscale 3D resolutions. Here, with adaptive phase retrievals on independent data sets with different sampling frequencies, we introduce multidistance coherent X-ray tomography as a noninvasive and quantitative nanoprobe to realize high-resolution 3D imaging of micrometer-sized specimens. The 3D density distribution of an entire mesoporous silica nanoparticle was obtained at 13 nm 3D resolution for quantitative physical and morphological analyses of its 3D pore structure. The morphological features of the whole 3D pore network and pore connectivity were examined to gain insight into the potential functions of the particles. The proposed multidistance tomographic imaging scheme with quantitative structural analyses is expected to advance studies of functional materials by facilitating their structure-based rational design.

Randomized, multicenter, parallel, open, phase 4 study to compare the efficacy and safety of rosuvastatin/amlodipine polypill versus atorvastatin/amlodipine polypill in hypertension patient with dyslipidemia.

The authors performed this study to investigate the efficacy and safety of a rosuvastatin (RSV)/amlodipine (AML) polypill compared with those of atorvastatin (ATV)/AML polypill. We included 259 patients from 21 institutions in Korea. Patients were randomly assigned to 1 of 3 treatment groups: RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, or ATV 20 mg /AML 5 mg. The primary endpoint was the efficacy of the RSV 10.20 mg/AML 5 mg via percentage changes in LDL-C after 8 weeks of treatment, compared with the ATV 20 mg /AML 5 mg. There was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 10 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (full analysis set [FAS]: -7.08%, 95% CI: -11.79 to -2.38, p = .0034, per-protocol analysis set [PPS]: -6.97%, 95% CI: -11.76 to -2.19, p = .0046). Also, there was a significant difference in the mean percentage change of LDL-C at 8 weeks between the RSV 20 mg/AML 5 mg and the ATV 20 mg/AML 5 mg (FAS: -10.13%, 95% CI: -15.41 to -4.84, p = .0002, PPS: -10.96%, 95% CI: -15.98 to -5.93, p < .0001). There was no significant difference in the adverse events rates between RSV 10 mg/AML 5 mg, RSV 20 mg/AML 5 mg, and ATV 20 mg/AML 5 mg. In conclusion, while maintaining safety, RSV 10 mg/AML 5 mg and the RSV 20 mg/AML 5 mg more effectively reduced LDL-C compared with the ATV 20 mg /AML 5 mg (Clinical trial: NCT03951207).

Prediction of Extrusion Machine Stem Fatigue Life Using Structural and Fatigue Analysis.

In this study, the characteristics of the SKD61 material used for the stem of an extruder were analyzed through structural analysis, tensile testing, and fatigue testing. The extruder works by pushing a cylindrical billet into a die with a stem to reduce its cross-sectional area and increase its length, and it is currently used to extrude complex and diverse shapes of products in the field of plastic deformation processes. Finite element analysis was used to determine the maximum stress on the stem, which was found to be 1152 MPa, lower than the yield strength of 1325 MPa obtained from tensile testing. Fatigue testing was conducted using the stress-life (S-N) method, considering the characteristics of the stem, and statistical fatigue testing was employed to create an S-N curve. The predicted minimum fatigue life of the stem at room temperature was 424,998 cycles at the location with the highest stress, and the fatigue life decreased with increasing temperature. Overall, this study provides useful information for predicting the fatigue life of extruder stems and improving their durability.

Sex-related impact on clinical outcomes of patients treated with drug-eluting stents according to clinical presentation: Patient-level pooled analysis from the GRAND-DES registry.

BACKGROUND: The contribution of sex and initial clinical presentation to the long-term outcomes in patients undergoing percutaneous coronary intervention (PCI) is still debated. METHODS: Individual patient data from 5 Korean-multicenter drug-eluting stent (DES) registries (The GRAND-DES) were pooled. A total of 17,286 patients completed 3-year follow-up (5216 women and 12,070 men). The median follow-up duration was 1125 days (interquartile range 1097-1140 days), and the primary endpoint was cardiac death at 3 years. RESULTS: The clinical indication for PCI was stable angina pectoris (SAP) in 36.8%, unstable angina pectoris (UAP) or non-ST-segment elevation myocardial infarction (NSTEMI) in 47.4%, and ST-segment elevation myocardial (STEMI) in 15.8%. In all groups, women were older and had a higher proportion of hypertension and diabetes mellitus compared with men. Women presenting with STEMI were older than women with SAP, with the opposite seen in men. There was no sex difference in cardiac death for SAP or UAP/NSTEMI. In STEMI patients, the incidence of cardiac death (7.9% vs. 4.4%, p = 0.001), all-cause mortality (11.1% vs. 6.9%, p = 0.001), and minor bleeding (2.2% vs. 1.2%, p = 0.043) was significantly higher in women. After multivariable adjustment, cardiac death was lower in women for UAP/NSTEMI (HR 0.69, 95% CI 0.53-0.89, p = 0.005), while it was similar for STEMI (HR 0.97, 95% CI 0.65-1.44, p = 0.884). CONCLUSIONS: There was no sex difference in cardiac death after PCI with DES for SAP and UAP/NSTEMI patients. In STEMI patients, women had worse outcomes compared with men; however, after the adjustment of confounders, female sex was not an independent predictor of mortality.

Body Mass Index and Major Adverse Events During Chronic Antiplatelet Monotherapy After Percutaneous Coronary Intervention With Drug-Eluting Stents　- Results From the HOST-EXAM Trial.

BACKGROUND: This study evaluated the association of body mass index (BMI) with adverse clinical outcomes during chronic maintenance antiplatelet monotherapy after percutaneous coronary intervention (PCI) with drug-eluting stents (DES).Methods and Results: Overall, 5,112 patients were stratified (in kg/m2) into underweight (BMI ≤18.4), normal weight (18.5-22.9), overweight (23.0-24.9), obesity (25.0-29.9) and severe obesity (≥30.0) categories with randomized antiplatelet monotherapy of aspirin 100 mg or clopidogrel 75 mg once daily for 24 months. The primary endpoint was the composite of all-cause death, non-fatal myocardial infarction, stroke, readmission due to acute coronary syndrome and major bleeding of Bleeding Academic Research Consortium type ≥3. Compared with normal weight, the risk of primary composite outcomes was higher in the underweight (hazard ratio [HR] 2.183 [1.199-3.974]), but lower in the obesity (HR 0.730 [0.558-0.954]) and severe obesity (HR 0.518 [0.278-0.966]) categories, which is partly driven by the difference in all-cause death. The risk of major bleeding was significantly higher in the underweight (HR 4.140 [1.704-10.059]) than in the normal weight category. A decrease in categorical BMI was independently associated with the increased risk of primary composite outcomes. CONCLUSIONS: Lower BMI is associated with a higher risk of primary composite outcomes, which is primarily related to the events of all-cause death or major bleeding during chronic maintenance antiplatelet monotherapy after PCI with DES.

A Multicenter, Randomized, Double-blind, Active-controlled, Factorial Design, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Combination Therapy of Pitavastatin and Ezetimibe Versus Monotherapy of Pitavastatin in Patients With Primary Hypercholesterolemia.

PURPOSE: Pitavastatin is a unique lipophilic statin with moderate efficacy in lowering LDL-C levels by 30% to 50% with a tolerable safety profile. However, the efficacy of adding ezetimibe to pitavastatin in patients with dyslipidemia has not been well investigated. Therefore, the objective of this double-blind, multicenter, randomized, Phase III study was to compare the efficacy and safety of pitavastatin and ezetimibe combination therapy with those of pitavastatin monotherapy in Korean patients with primary hypercholesterolemia. METHODS: Korean men and women aged >19 and <80 years with primary hypercholesterolemia requiring medical treatment were included in this study. During the 8-week screening period, all patients were instructed to make therapeutic lifestyle changes. The screening period consisted of a 4-week washout period and a placebo run-in period (4-8 weeks). During treatment period I, patients were randomly assigned to receive 1 of 4 treatments: pitavastatin 2 mg plus ezetimibe 10 mg, pitavastatin 2 mg, pitavastatin 4 mg plus ezetimibe 10 mg, or pitavastatin 4 mg. The 8-week double-blind treatment period then commenced. Adverse events (AEs), clinical laboratory data, and vital signs were assessed in all patients. FINDINGS: The percentages in LDL-C from baseline after 8 weeks of double-blind treatment decreased significantly in the pooled pitavastatin/ezetimibe (-52.8% [11.2%]) and pooled pitavastatin (-37.1% [14.1%]) groups. Treatment with pitavastatin/ezetimibe resulted in a significantly greater LDL-C-lowering effect than that with pitavastatin (difference, -15.8 mg/dL; 95% CI, -18.7 to -12.9; P < 0.001). The precentages of achieving LDL-C goal in pooled pitavastatin/ezetimibe and pooled pitavastatin groups were 94.2% and 69.1%, respectively (P < 0.001). There were no significant differences in the incidence of overall AEs and adverse drug reactions. Serious AEs were comparable between the groups. IMPLICATIONS: Pitavastatin and ezetimibe combinations effectively and safely decreased LDL-C levels by >50% in patients with dyslipidemia. The safety and tolerability of pitavastatin and ezetimibe combination therapy were comparable with those of pitavastatin monotherapy. CLINICALTRIALS: gov identifier: NCT04584736.

Durable polymer versus biodegradable polymer drug-eluting stents in patients with acute coronary syndrome undergoing complex percutaneous coronary intervention: a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS trial.

BACKGROUND: Comparative data of durable polymer (DP) versus biodegradable polymer (BP) drug-eluting stents (DES) are limited in patients presenting with acute coronary syndrome (ACS) undergoing complex percutaneous coronary intervention (PCI). AIMS: We sought to evaluate the efficacy and safety of DP-DES and BP-DES in ACS patients receiving complex PCI. METHODS: This study was a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS trial. ACS patients were randomly assigned 1:1 to DP-DES or BP-DES in the HOST-REDUCE-POLYTECH-ACS trial. Complex PCI was defined as having at least 1 of the following features: ≥3 stents implanted, ≥3 lesions treated, total stent length ≥60 mm, bifurcation PCI with 2 stents, left main PCI, or heavy calcification. Patient-oriented (POCO, a composite of all-cause death, non-fatal myocardial infarction, and any repeat revascularisation) and device-oriented composite outcomes (DOCO, a composite of cardiac death, target vessel myocardial infarction, or target lesion revascularisation) were evaluated at 12 months. RESULTS: Among 3,301 patients for whom full procedural data were available, 1,140 patients received complex PCI. Complex PCI was associated with higher risks of POCO and DOCO. The risks of POCO were comparable between DP-DES and BP-DES in both the complex (HR 0.87, 95% confidence interval [CI]: 0.57-1.33; p=0.522) and non-complex (HR 0.83, 95% CI: 0.56-1.24; p=0.368; p for interaction=0.884) PCI groups. DOCO was also not significantly different between DP-DES and BP-DES in both the complex (HR 0.74, 95% CI: 0.43-1.27; p=0.278) and non-complex (HR 0.67, 95% CI: 0.38-1.19; p=0.175; p for interaction=0.814) PCI groups. CONCLUSIONS: In ACS patients, DP-DES and BP-DES showed similar clinical outcomes irrespective of PCI complexity.

Efficacy and Safety of 3 Versus 6 Months of Dual-Antiplatelet Therapy in Patients Implanted With a Coroflex ISAR Stents: A Prospective, Multicenter, Randomized Clinical Trial.

BACKGROUND: The optimal duration of dual-antiplatelet therapy (DAPT) after implantation of a drug-eluting stent (DES), especially recently developed polymer-free DESs, is unknown. This study examined the efficacy and safety of 3- versus 6-month DAPT in patients implanted with Coroflex ISAR polymer-free DESs. METHODS: Between May 2015 and August 2020, 488 patients who underwent Coroflex ISAR stent implantation were enrolled in the study and randomly assigned to the 3-month (n=244) or 6-month (n=244) DAPT group. RESULTS: At 1 year, the primary endpoint (composite of cardiovascular death, myocardial infarction, target vessel revascularization, and Bleeding Academic Research Consortium [BARC] type 2-5 bleeding) occurred in 9 (3.7%) patients in the 3-month DAPT group and in 7 (2.9%) patients in the 6-month DAPT group (hazard ratio 1.31; P=.60). There was no difference between the 3- and 6-month DAPT groups in either BARC type 2-5 bleeding (1.6% vs 0.8%; hazard ratio 2.00; P=.42) or any bleeding (2.9% vs 3.3%; hazard ratio 0.87; P=.80). CONCLUSION: Compared with 6 months of DAPT, 3 months of DAPT did not increase the risk of primary endpoint 1 year after Coroflex ISAR stent implantation, although it should be noted that the trial has limited power to see differences due to low event rate and low recruitment rate.

The Clinical Impact of ß-Blocker Therapy on Patients With Chronic Coronary Artery Disease After Percutaneous Coronary Intervention.

BACKGROUND AND OBJECTIVES: The outcome benefits of ß-blockers in chronic coronary artery disease (CAD) have not been fully assessed. We evaluated the prognostic impact of ß-blockers on patients with chronic CAD after percutaneous coronary intervention (PCI). METHODS: A total of 3,075 patients with chronic CAD were included from the Grand Drug-Eluting Stent registry. We analyzed ß-blocker prescriptions, including doses and types, in each patient at 3-month intervals from discharge. After propensity score matching, 1,170 pairs of patients (ß-blockers vs. no ß-blockers) were derived. Primary outcome was defined as a composite endpoint of all-cause death and myocardial infarction (MI). We further analyzed the outcome benefits of different doses (low-, medium-, and high-dose) and types (conventional or vasodilating) of ß-blockers. RESULTS: During a median (interquartile range) follow-up of 3.1 (3.0-3.1) years, 134 (5.7%) patients experienced primary outcome. Overall, ß-blockers demonstrated no significant benefit in primary outcome (hazard ratio [HR], 0.88; 95% confidence interval [CI], 0.63-1.24), all-cause death (HR, 0.87; 95% CI, 0.60-1.25), and MI (HR, 1.25; 95% CI, 0.49-3.15). In subgroup analysis, ß-blockers were associated with a lower risk of all-cause death in patients with previous MI and/or revascularization (HR, 0.38; 95% CI, 0.14-0.99) (p for interaction=0.045). No significant associations were found for the clinical outcomes with different doses and types of ß-blockers. CONCLUSIONS: Overall, ß-blocker therapy was not associated with better clinical outcomes in patients with chronic CAD undergoing PCI. Limited mortality benefit of ß-blockers may exist for patients with previous MI and/or revascularization. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03507205.

Prasugrel Dose De-escalation Therapy After Complex Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: A Post Hoc Analysis From the HOST-REDUCE-POLYTECH-ACS Trial.

Importance: De-escalation of dual-antiplatelet therapy through dose reduction of prasugrel improved net adverse clinical events after acute coronary syndrome (ACS), mainly through the reduction of bleeding without an increase in ischemic outcomes. However, whether such benefits are similarly observed in those receiving complex procedures is unknown. Objective: To investigate whether the benefits of prasugrel dose de-escalation therapy are maintained in the complex percutaneous coronary intervention (PCI) subgroup. Design, Setting, and Participants: This was a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS trial, a randomized, open-label, adjudicator-blinded, multicenter trial performed at 35 hospitals in South Korea. Study participants included patients with ACS who were receiving PCI. Data were collected from September 30, 2014, to December 18, 2015, and analyzed from September 17, 2020, to June 15, 2021. Interventions and Exposures: Patients were randomized to a prasugrel dose de-escalation (5 mg daily) at 1 month post-PCI group or a conventional (10 mg daily) group. Complex PCI was defined as having at least 1 of the following features: 3 or more stents implanted, 3 or more lesions treated, bifurcation PCI, total stent length 60 mm or larger, left main PCI, or heavy calcification. Main Outcomes and Measures: The main analysis end points were MACE (major adverse cardiac event, a composite of cardiovascular death, nonfatal myocardial infarction, stent thrombosis, and repeat revascularization) at 1 year for ischemic outcomes, and BARC (Bleeding Academic Research Consortium) class 2 or higher bleeding events at 1 year for bleeding outcomes. Results: Of 2271 patients (mean [SD] age, 58.9 [9.0] years; 2024 [89%] male patients) for whom full procedural data were available, 705 patients received complex PCI, and 1566 patients received noncomplex PCI. Complex PCI was associated with higher rates of ischemic outcomes but not with bleeding outcomes. Prasugrel dose de-escalation did not increase the risk of MACE (hazard ratio [HR], 0.88; 95% CI, 0.47-1.66; P = .70 in complex PCI; HR, 0.81; 95% CI, 0.45-1.46; P = .48 in noncomplex PCI; P for interaction = .84) but decreased BARC class 2 or higher bleeding events (HR, 0.25; 95% CI, 0.10-0.61; P = .002 in complex PCI; HR, 0.62; 95% CI, 0.38-1.00; P = .05 in noncomplex PCI; P for interaction = .08), albeit with wide 95% CIs. Conclusions and Relevance: In this post hoc analysis of patients with ACS, prasugrel dose de-escalation compared with conventional therapy was not associated with an increased risk of ischemic outcomes but may reduce the risk of minor bleeding events at 1 year, irrespective of PCI complexity. Trial Registration: ClinicalTrials.gov Identifier: NCT02193971.

Impact of chronic kidney disease on clinical outcomes in patients with Stage B progressive aortic regurgitation (mild to moderate and moderate grades).

BACKGROUND: Chronic kidney disease (CKD) is a significant comorbidity in patients with heart failure and valvular heart disease. Renal impairment is not well evaluated in the patients with Stage B progressive aortic regurgitation (AR) (mild to moderate and moderate grades in this study), for estimating outcome. HYPOTHESIS: We sought to investigate the prognostic factor, especially CKD, in the patients with progressive AR. METHODS: We enrolled 262 patients with Stage B progressive AR and preserved left ventricular systolic function (ejection fraction ≥ 50%). Based on the presence of CKD, the patients were divided into CKD (n = 70) and non-CKD (n = 192) groups, which CKD was defined as estimated glomerular filtration rate < 60 ml/min/1.73 m2 . The primary outcome was major adverse cardiac events (MACEs), including cardiac death, myocardial infarction, hospitalization for heart failure, and aortic valve replacement. RESULTS: The median follow-up duration was 41.5 (interquartile range: 16.2-71.7) months. Between groups, the CKD patients were older; they had a higher pulse pressure and higher incidence of hypertension, diabetes mellitus, dyslipidemia, cerebrovascular accident, and atrial fibrillation. Compared to the non-CKD group, the CKD group had lower e' velocity (4.36 ± 2.21 vs. 5.20 ± 2.30 cm/s, p = .009), higher right ventricular systolic pressure (38.02 ± 15.79 vs. 33.86 ± 11.77 mmHg, p = .047). The CKD group was associated with increased risk of MACEs (41.4% vs. 22.4%; unadjusted hazard ratio [HR]: 1.78, 95% confidence interval [CI]: 1.11-2.85, p = .017). In multivariate Cox regression analyses, the risk of MACEs was significantly different between groups (adjusted HR: 1.71, 95% CI: 1.11-2.62, p = .015); furthermore, the risk of hospitalization for heart failure (10.0% vs. 2.6%; adjusted HR: 2.30, 95% CI: 1.16-4.55, p = .017) was significantly higher in the CKD group than in the non-CKD group. CONCLUSIONS: In patients with Stage B progressive AR, CKD is an independent prognostic factor for clinical outcomes (composite clinical outcome, hospitalization for heart failure).

Algorithm for diagnosing hypertension using out-of-office blood pressure measurements.

The authors developed and validated a diagnostic algorithm using the optimal upper and lower cut-off values of office and home BP at which ambulatory BP measurements need to be applied. Patients presenting with high BP (≥140/90 mm Hg) at the outpatient clinic were referred to measure office, home, and ambulatory BP. Office and home BP were divided into hypertension, intermediate (requiring diagnosis using ambulatory BP), and normotension zones. The upper and lower BP cut-off levels of intermediate zone were determined corresponding to a level of 95% specificity and 95% sensitivity for detecting daytime ambulatory hypertension by using the receiver operator characteristic curve. A diagnostic algorithm using three methods, OBP-ABP: office BP measurement and subsequent ambulatory BP measurements if office BP is intermediate zone; OBP-HBP-ABP: office BP, subsequent home BP measurement if office BP is within intermediate zone and subsequent ambulatory BP measurement if home BP is within intermediate zone; and HBP-ABP: home BP measurement and subsequent ambulatory BP measurements if home BP is within intermediate zone, were developed and validated. In the development population (n = 256), the developed algorithm yielded better diagnostic accuracies than 75.8% (95%CI 70.1-80.9) for office BP alone and 76.2% (95%CI 70.5-81.3) for home BP alone as follows: 96.5% (95%CI: 93.4-98.4) for OBP-ABP, 93.4% (95%CI: 89.6-96.1) for OBP-HBP-ABP, and 94.9% (95%CI: 91.5-97.3%) for HBP-ABP.  In the validation population (n = 399), the developed algorithm showed similarly improved diagnostic accuracy. The developed algorithm applying ambulatory BP measurement to the intermediate zone of office and home BP improves the diagnostic accuracy for hypertension.

A Randomized, Double-blind, Active-controlled, Two Parallel-Group, Optional Titration, Multicenter, Phase IIIb Study to Evaluate the Efficacy and Safety of Fimasartan Versus Perindopril Monotherapy With and Without a Diuretic Combination in Elderly Patients With Essential Hypertension.

PURPOSE: The efficacy and tolerability of fimasartan in elderly patients have not been fully evaluated. This study was therefore conducted to determine the efficacy and tolerability of fimasartan compared with perindopril in elderly Korean patients aged >70 years with essential hypertension (defined by a mean sitting systolic blood pressure [SBP] ≥140 mm Hg). METHODS: This randomized, double-blind, active-controlled, 2 parallel-group, optional titration, multicenter, Phase IIIb trial (FITNESS [Fimasartan in the Senior Subjects]) enrolled 241 patients from 23 cardiac centers in the Republic of Korea between August 2017 and December 2019. After the placebo run-in period, treatment started with fimasartan 30 mg or perindopril arginine 2.5 mg once daily at a 1:1 ratio; if BP was not controlled at week 4, the dose was doubled. If BP was not controlled at week 8, a diuretic combination (fimasartan 60 mg/hydrochlorothiazide 12.5 mg or perindopril arginine 5 mg/indapamide 1.25 mg) was administered. After 16 weeks of the double-blind treatment, the patients with controlled BP participated in an 8-week open-label extension study, with the 2 groups unified by fimasartan 60 mg with or without hydrochlorothiazide 12.5 mg for 8 weeks. The primary outcome was a change in SBP for 8 weeks. The secondary outcomes included a change in sitting diastolic BP (DBP) for 8 weeks and changes in SBP and DBP for 4, 16, and 24 weeks. FINDINGS: At week 8, mean SBP significantly decreased from baseline in both groups: -14.2 (14.4) mm Hg in the fimasartan group and -9.0 (16.1) mm Hg in the perindopril group. The difference between the 2 groups was 5.4 (2.1) mm Hg, indicating the noninferiority of fimasartan to perindopril. Moreover, fimasartan exhibited a higher BP-lowering effect than perindopril (P = 0.0108). In addition, reductions in SBP and DBP from baseline to weeks 4, 8, and 16 were significantly greater in the fimasartan group than in the perindopril group, although the SBP reduction was comparable at week 16. Both groups reported an excellent mean compliance rate of 97.4% (4.7%) through week 16. During the study period, 82 adverse events were reported in 52 patients, 40 in the fimasartan group and 42 in the perindopril group (P = 0.4647). Dizziness was the most commonly reported adverse event (7 cases). Remarkably, only 1 case of orthostatic hypotension was reported during the study period. IMPLICATIONS: In elderly patients with essential hypertension, fimasartan 30 to 60 mg with a possible hydrochlorothiazide 12.5-mg combination was noninferior to perindopril 2.5 to 5 mg with a possible indapamide 1.25-mg combination. Furthermore, fimasartan exhibited higher BP-lowering efficacy than perindopril. There was no difference in tolerability between the 2 groups. Clinicaltrials.gov Identifier: NCT03246555.

Safety and usefulness of a novel short track sliding balloon catheter.

OBJECTIVES: To evaluate the safety and technical utility of the short track sliding (STS) balloon catheter. BACKGROUND: An STS balloon catheter is designed to ensure a low profile at the shaft and perform distal anchoring using a single guidewire. However, its clinical practice with the STS balloon catheter has not been reported. METHODS: This prospective multi-center registry enrolled 100 patients with significant coronary artery disease who had undergone percutaneous coronary intervention using an STS balloon catheter at three hospitals in Korea from March 2019 to July 2020. Overall safety was assessed as any occurrences of device-related malfunction during the pre-dilation of the lesions. Its technical success rates of the kissing balloon technique or the distal anchoring technique using a single guidewire were also evaluated. RESULTS: Of the 118 lesions pre-dilated using the STS balloon, no significant complication was observed except for three significant coronary dissections, which were completely covered with stents. There was no incidence of balloon catheter malfunction, such as fracture, entrapment, or perforation. With 13 attempts of kissing ballooning techniques with the STS balloon with a 6F guiding catheter, all cases were successful. The distal anchoring techniques were attempted in 10 cases, the stent was successfully crossed to the target lesion in all 10 cases. CONCLUSIONS: The novel STS balloon catheter can be safely applied in routine coronary intervention with minimal complications. In addition, this catheter could be useful for performing the kissing balloon technique with a small-caliber guiding catheter and distal anchoring technique with a single guidewire.

Predictors of Favorable Angiographic Outcomes After Drug-Coated Balloon Use for de novo Small Vessel Coronary Disease (DCB-ONLY).

We evaluated the angiographic parameter and clinical outcomes of drug-coated balloon (DCB) to assess the optimal angiographic criteria in de novo small vessel disease (SVD). Patients (n = 424, mean age: 64.4 ± 11.2 years, men: 69.8%) at 20 sites in Korea were prospectively enrolled. The primary end point was late luminal loss (LLL) at 9-month follow-up angiography. Secondary end points included restenosis rates, target lesion failure (TLF), and DCB-related thrombosis during the 12-month follow-up period. We included 403 patients for analysis excluding 21 patients who required bailout stenting. Baseline mean reference vessel .diameter was 2.52 ± 0.39 mm and mean minimal luminal diameter (MLD) was 0.71 ± 0.40 mm. The mean MLD was 1.54 ± 0.37 mm after DCB. Late luminal loss was -0.01 ± 0.43 mm and restenosis was noted in 26 patients (12.2%). Minimal luminal diameter >1.6 mm and %diameter stenosis (DS) <45% after DCB was associated maintenance of MLD without LLL at 9-months. Multivariate analysis demonstrated that %DS at baseline and post-MLD was associated with the restenosis. During 12-month follow-up, TLF was 2.6% including 1 cardiac death, 1 myocardial infarction, and 10 ischemia-driven target lesion revascularizations. Drug-coated balloon showed a low restenosis and lower LLL despite high in-segment DS. Post-MLD and % DS may be helpful to get optimal results in de novo SVD after DCB.

Adherence to triple-component antihypertensive regimens is higher with single-pill than equivalent two-pill regimens: A randomized controlled trial.

Using a single-pill combination (SPC) for hypertension (HTN) treatment resulted in better adherence and persistence than a free-equivalent combination in previous observational studies. The aim of this study is to confirm superior adherence with a triple-component SPC compared with an equivalent two-pill regimen in a randomized controlled trial (RCT) using a medication event monitoring system (MEMS). This is a multicenter, open-label, RCT. Subjects were persons with HTN whose clinic blood pressure was not adequately controlled (systolic >140 mmHg or diastolic >90 mmHg) with a dual combination. Eligible patients were randomized to either the triple-component SPC (olmesartan/amlodipine/hydrochlorothiazide 20/5/12.5 mg) group or the equivalent two-pill (olmesartan/hydrochlorothiazide 20/12.5 mg + amlodipine 5 mg) group and maintained for 12 weeks. Primary outcomes were the difference in percentage of doses taken (PDT) and percentage of days with the prescribed dose taken correctly (PDTc) between the single- and two-pill therapy groups, calculated from MEMS data. From 8 hospitals, 145 patients with HTN were randomized. The single-pill group had significantly higher PDT and PDTc than the two-pill group: median (25-75 percentile) PDT 95.1 (86.7-100.0) versus 92.1 (73.0-97.3); and PDTc 91.0 (79.4-96.5) versus 88.6 (69.2-96.3%), P = 0.04 for both by the Wilcoxon rank sum test. The single-pill combination of the triple-component antihypertensive regimen showed better adherence than the equivalent two-pill therapy. Reducing pill burden by means of a single-pill combination is an effective strategy for enhancing adherence to multiple-agent antihypertensive therapy. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Previous studies suggested that the use of a single-pill combination (SPC) in hypertension (HTN) treatment produced better adherence and persistence than a free-equivalent combination. However, supportive data are confined to dual-component SPC and came from observational studies using medication possession ratio as an outcome. WHAT QUESTION DID THIS STUDY ADDRESS? The objective of this study is to investigate whether a triple-component SPC improved medication adherence over an equivalent two-pill combination therapy in a randomized controlled trial using medication event monitoring systems. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Medication adherence in the SPC group was superior to that of two-pill group, confirming previous findings from observational studies. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? This finding strongly supports the current HTN treatment guideline to prefer SPC with a higher level of evidence.

High-Throughput 3D Ensemble Characterization of Individual Core-Shell Nanoparticles with X-ray Free Electron Laser Single-Particle Imaging.

The structures as building blocks for designing functional nanomaterials have fueled the development of versatile nanoprobes to understand local structures of noncrystalline specimens. Progress in analyzing structures of individual specimens with atomic scale accuracy has been notable recently. In most cases, however, only a limited number of specimens are inspected lacking statistics to represent the systems with structural inhomogeneity. Here, by employing single-particle imaging with X-ray free electron lasers and algorithms for multiple-model 3D imaging, we succeeded in investigating several thousand specimens in a couple of hours and identified intrinsic heterogeneities with 3D structures. Quantitative analysis has unveiled 3D morphology, facet indices, and elastic strain. The 3D elastic energy distribution is further corroborated by molecular dynamics simulations to gain mechanical insight at the atomic level. This work establishes a route to high-throughput characterization of individual specimens in large ensembles, hence overcoming statistical deficiency while providing quantitative information at the nanoscale.