Detecting T-cell receptor clonality in patients with severe atopic dermatitis refractory to dupilumab.

BACKGROUND: Trials and real-life studies demonstrated clinically meaningful improvements of disease activity in the majority of patients with moderate to severe atopic dermatitis (AD) treated with the anti-IL-4RA-antibody dupilumab. However, misdiagnosis or confounding skin diseases in particular cutaneous T-cell lymphoma (CTCL) may lead to inadequate response. OBJECTIVE: To investigate the clinical and pathological features of patients with AD who showed insufficient response to dupilumab. METHODS: We reviewed the medical records of 371 patients treated with dupilumab for severe AD. Insufficient response was defined as failure to achieve an improvement of the eczema area severity index (EASI) of at least 50% (EASI-50) at Week 16 and of 75% (EASI-75) at Week 52. Among 46 patients with insufficient response, 35 patients consented to a re-evaluation including a full physical exam, biopsies and laboratory assessments including immunohistochemistry and T-cell receptor gene rearrangement analysis to differentiate CTCL. RESULTS: Of the 371 patients treated with dupilumab, 46 (12.3%) patients showed insufficient response to dupilumab. Of these, 35 underwent further evaluation, and 19 (54.2% of inadequate responders) were finally diagnosed with mycosis fungoides (MF). In these patients, transition to or addition of conventional MF treatment led to clinical improvements. CONCLUSIONS: Insufficient response to dupilumab treatment may help uncover early MF on an existing AD background.

Drug Eluting Stent vs. Drug Coated Balloon for Native Femoropopliteal Artery Disease: A Two Centre Experience.

OBJECTIVE: There have been limited clinical trials comparing drug eluting stents (DESs) and drug coated balloons (DCBs) in the treatment of femoropopliteal artery disease. This two centre retrospective and prospective cohort study sought to compare DES with DCB for the treatment of native femoropopliteal artery disease. METHODS: A total of 288 limbs (242 patients) with native femoropopliteal artery disease were treated with DESs (Zilver PTX; 102 limbs) or DCBs (IN.PACT Admiral; 186 limbs) in two Korean endovascular centres between 19 January 2013 and 5 May 2018 and followed for a median duration of 19.6 months. The primary endpoint was primary clinical patency. Propensity score matching (PSM, 162 limbs) and inverse probability weighted (IPW) adjustment were performed to adjust for confounding baseline characteristics. RESULTS: The DCB group had fewer lesions with Trans-Atlantic Inter-Society Consensus (TASC) II type C/D (55.9% vs. 70.6%, p = .021) or total occlusions (43.5% vs. 77.5%, p < .001) and showed shorter lesion lengths (164.2 ± 105.4 mm vs. 194.8 ± 86.8 mm, p = .009) than the DES group. After PSM, baseline clinical and lesion characteristics of the two groups were comparable except for larger reference vessel diameter in the DES group (5.4 ± 0.6 vs. 5.1 ± 0.7, p = .025). Adjunctive atherectomy was performed in 32.1% of the DCB group and in 2.5% of the DES group (p < .001). The provisional stenting was required in 14.8% of the DCB group. At two year follow up, the DCB group showed higher primary clinical patency (74.6% vs. 56.7%, hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.27-0.96, p = .032) and freedom from target lesion revascularisation (85.9% vs. 71.3%, HR 0.39, 95% CI 0.17-0.89, p = .021) than the DES group. Survival from all cause death did not differ between groups (87.6% vs. 92.1%, HR 1.85, 95% CI 0.62-5.52, p = .26). CONCLUSION: In this two centre cohort, DCBs with selective use of adjunctive atherectomy achieved more favourable outcomes than DESs for native femoropopliteal artery disease.

A comparison between drug-eluting stent implantation and drug-coated balloon angioplasty in patients with left main bifurcation in-stent restenotic lesions.

BACKGROUND: The current guidelines recommend both repeat stenting and drug-coated balloons (DCB) for in-stent restenosis (ISR) lesions, if technically feasible. However, real-world clinical data on the interventional strategies in patients with left main bifurcation (LMB)-ISR have not been elucidated. METHODS: Seventy-five patients with LMB-ISR, who underwent percutaneous coronary intervention (PCI) between January 2009 and July 2015, were retrospectively reviewed for the present study (repeat drug eluting stent [DES] implantation [n = 51], DCB angioplasty [n = 24]). RESULTS: Analysis of the baseline characteristics showed that the patients in the DCB group had a lower incidence of non-ST segment elevation myocardial infarction/ST segment elevation myocardial infarction at the index PCI (8.3% vs. 25.5%; p = 0.12), higher low-density lipoprotein-cholesterol level (92.9 mg/dL vs. 81.7 mg/dL; p = 0.09), and more "stent-in-stent" lesions (25% vs. 7.8%; p = 0.07) than those in the DES group. A smaller post-procedural minimal target lesion lumen diameter was also noted in the DCB group than in the DES group (2.71 mm vs. 2.85 mm; p = 0.03). The cumulative incidence rates of major adverse cardiac events (MACEs) were similar between both groups (median follow-up duration, 868 days; MACE rate, 25% in the DCB group vs. 25.5% in the DES group; p = 0.96). The multivariate Cox regression analysis indicated that the true bifurcation of ISR was an independent risk predictor of MACEs (hazard ratio, 4.62; 95% confidence interval, 1.572-13.561; p < 0.01). CONCLUSIONS: DES and DCB showed comparable long-term clinical results in patients with LMB-ISR lesions.

Savior in Desperate Situation: Successful TAVI for Critically Ill Patient with Severe Aortic Stenosis and Concomitant Constrictive Pericarditis Accompanied by Radiation Dermatitis, Complicated by Cold Abscess in Anterior Chest Wall.

BACKGROUND: Constrictive pericarditis (CP) can coexist with severe aortic stenosis (AS), especially in patients with previous mediastinal radiation. Because impaired diastolic filling by CP may aggravate hemodynamic abnormalities from severe AS, leading to very low cardiac output, concomitant AS and CP result in a critical debilitating condition and pose a challenge to therapy. CASE REPORT: A 79-year-old woman was brought to our hospital with New York Heart Association class IV dyspnea and severe frailty (clinical frailty scale 8). She had a history of chronic constrictive pericarditis, severe aortic stenosis with reduced left ventricular systolic function (ejection fraction 40%), paroxysmal atrial fibrillation, diabetes mellitus, and radiation dermatitis complicated by a cold abscess in the anterior chest wall from previous mediastinal radiation. She continually complained of dizziness, general weakness, and dyspnea despite optimal medical treatment, and her symptoms worsened recently while bedridden. Although simultaneous surgical pericardiectomy and aortic valve replacement is curative treatment, and the surgical risk was not high (Society of Thoracic Surgery score 4.745), her other comorbidities (radiation dermatitis, cold abscess, and severe frailty) eliminated the possibility of surgical treatment. Therefore, we decided on palliative treatment for CP after performing transcatheter aortic valve implantation (TAVI) for severe AS. We could not predict how she would recover from these conditions and were concerned about the high procedural risk associated with TAVI. Indeed, the patient had cardiac arrest during the TAVI procedure, and we implanted a 31-mm CoreValve while performing cardiac massage. After the patient recovered from cardiac arrest, we safely completed the TAVI procedure with a temporary pacemaker because of complete atrioventricular block. She recovered remarkably after TAVI with permanent pacemaker implantation, and is now able to walk without support. CONCLUSION: Reduced diastolic filling by chronic CP aggravates hemodynamic deterioration through severe AS, leading to a very serious debilitating condition including severe frailty and decompensated heart failure. Although surgical pericardiectomy and aortic valve replacement are recommended as optimal therapy, TAVI alone can be an alternative therapeutic option if surgery is not possible.

Unnecessary PCI Attempt for Presumed CTO Which Was Revealed To Be Anomalous Coronary Arteries - Role of Coronary CT Angiography.

Herein, we present a brief case of anomalous coronary arteries mistaken to be chronic total occlusion. Since we first presumed the anomalous coronary arteries to be chronic total occlusion of the distal right coronary artery, percutaneous coronary intervention was attempted for the presumed lesion, but it failed. Before the second attempt of percutaneous coronary intervention, coronary computed tomography angiography revealed the coronary artery from the left anterior descending artery corresponding with the distal part of the right coronary artery without connection to the right coronary artery. Therefore, we recognized the patient had anomalous coronary arteries with no connection of the vascular wall between the main and distal segments of the right coronary artery. This case may give insights to the importance of meticulous examination of coronary computed tomography angiography imaging before chronic total occlusion percutaneous coronary intervention to avoid the unnecessary procedure.

Incidence of new-onset diabetes with 1 mg versus 4 mg pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up.

BACKGROUND: Statin therapy reduces the risk of cardiovascular events across a broad spectrum of patients; however, it increases the risk of new-onset diabetes (NOD). Although the highest dose pitavastatin is considered to not be associated with NOD, there are limited data regarding the impact of long-term highest dose pitavastatin use on the development of NOD in patients at high risk of developing diabetes. Therefore, we prospectively compared the differences in the development of NOD between the lowest and the highest dose of pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up. METHODS: This post hoc analysis of a prospective, single-blinded, randomized study compared the risk of NOD between the highest dose of pitavastatin (4 mg) and the lowest dose of pitavastatin (1 mg) over a 3-year follow-up in patients with acute coronary syndrome. Among 1044 patients of the original study, 667 patients at high risk of developing type 2 diabetes mellitus were in the subgroup analysis. The primary endpoint was a comparison of the differences in the cumulative incidence of NOD in the pitavastatin 1 mg and 4 mg groups during a 3-year follow-up. RESULTS: With propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups. Incidence of NOD was similar between the pitavastatin 1 mg and 4 mg groups [12 of 289 patients (4.2%) and 8 of 289 patients (2.8%), respectively; p = 0.36]. In a prespecified analysis, there were no significant differences in NOD events according to sex, age, diagnosis, body mass index, glucose intolerance, or dyslipidemia. CONCLUSIONS: Administration of highest-dose pitavastatin did not increase the risk of NOD in patients at high risk of developing diabetes during the 3-year follow-up. Moreover, various risk factors for NOD such as metabolic syndrome components, glucose intolerance, dyslipidemia, obesity, or hypertension did not affect the development of NOD during pitavastatin administration. Thus, the highest dose pitavastatin can be safely used in patients with metabolic syndrome who are at high risk of developing diabetes. Trial registration Clinical Trial registration information. URL: https://clinicaltrials.gov/ct2/show/NCT02545231. Unique identifier: NCT02545231.

Impact of hyperuricemia on clinical outcomes after percutaneous coronary intervention for in-stent restenosis.

BACKGROUND: There have been limited data on the impact of hyperuricemia on long-term clinical outcomes after percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). METHODS: From January 2009 to July 2015, 317 patients who underwent repeat PCI for ISR were divided into two groups: patients with normal serum uric acid (UA) levels (normal UA group) and patients with higher serum UA levels (higher UA group). The higher UA group included patients with serum UA levels > 6.8 mg/dL or patients who were taking anti-hyperuricemic medication. RESULTS: During a median follow-up period of 1088 days, the cumulative incidence rates of major adverse event (MAE), including a composite of all-cause death, non-fatal myocardial infarction, and any revascularization, were similar between the two groups (higher UA 36.4% vs. normal UA 29.9%, p = 0.389, log-rank p = 0.367). Follow-up angiographic data showed similar outcomes of late lumen loss (0.8 ± 0.9 mm vs. 0.8 ± 1.1 mm, p = 0.895) and binary restenosis rate (28.1% vs. 34.7%, p = 0.622). Multivariate Cox regression analysis indicated higher levels of low-density lipoprotein cholesterol (hazard ratio [HR] 1.011, 95% confidence interval [CI] 1.003-1.019, p = 0.006) and lower left ventricular ejection fraction (HR 0.972, 95% CI 0.948-0.996, p = 0.022), but not UA levels, to be the independent risk predictors of MAE. CONCLUSION: Hyperuricemia is not associated with poor clinical outcomes after repeat PCI for ISR lesions.

Association of office blood pressure with ischemic and bleeding events in patients undergoing percutaneous coronary intervention.

Optimal blood pressure (BP) for patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI) remains unclear. This study aims to identify the optimal BP by investigating the association between average office BP and future clinical events in patients undergoing PCI. Consecutive patients undergoing PCI from 2012 to 2016 were included. They were divided into five groups according to the average follow-up BP after discharge. The co-primary outcomes were net adverse clinical events (NACE) and major adverse cardiac and cerebrovascular events (MACCE) up to 5 years. NACE was defined as a composite of MACCE (all-cause death, non-fatal myocardial infarction (MI), non-fatal stroke, or any revascularization) or major bleeding. A total of 2845 patients were included, and among them, 787 (27.7%) experienced the NACE during the follow-up period. Patients in the highest SBP group (adjusted hazard ratio [HR] 1.495, confidence interval [CI] 1.189-1.880) and lowest SBP group (adjusted HR 1.625, CI 1.214-2.176) had a significantly higher risk of 5-year NACE. Similar associations were observed between SBP and the risk of MACCE, and similar results based on DBP categories were also observed. There was a J-curve relationship between SBP and DBP with respect to 5-year NACE and MACCE. The nadir point of risk for NACE and MACCE was found at 121.4/74.8 and 120.4/73.7 mmHg. In patients underwent PCI, there is a significant correlation between office BP level and clinical events, indicates the importance of efforts for optimal BP control to reduce ischemic and bleeding events.Trial registration: HanYang University Medical Center (HYUMC) Registry, NCT05935397.

Comparing blood pressure measurements between sitting in chairs and sitting on the floor.

BACKGROUND: The current standard approach to measuring home blood pressure (BP) involves taking measurements while sitting in a chair. In cultures where floor sitting is common, including Korea, assessing BP while sitting on the floor would be more feasible. However, there is still a lack of research investigating whether BP measurements obtained while seated in a chair and while sitting on the floor can be regarded as interchangeable. The aim of the study was to evaluate whether there is a difference between BP measurements taken while sitting in a chair and while sitting on the floor in a Korean adult. METHODS: Among the participants who visited for evaluation of pulse wave velocity, a total of 116 participants who agreed to participate in the study were randomly selected. All subjects rested for 5 min, and BP measurements were taken at 1-min intervals according to a randomly assigned order of standard method (chair-sitting) and BP in a seated on the floor (floor-sitting). RESULTS: Of the 116 participants, the median age was 68 (with an interquartile range of 59 to 75), and 82% were men. There were no significant differences in systolic BP (SBP, 129.1 ± 17.8 mmHg in chair-sitting and 130.1 ± 18.9 mmHg in floor-sitting, P = 0.228) and diastolic BP (DBP, 73.9 ± 11.4 mmHg in chair-sitting and 73.7 ± 11.4 mmHg in floor-sitting, P = 0.839) between the two positions. In addition, there was a high level of agreement between BP measurements taken in the two positions (intraclass correlation coefficients: 0.882 for SBP and 0.890 for DBP). CONCLUSION: These findings provide important insights into securing the reliability of home BP measurements through the commonly practiced floor-sitting posture in cultures where floor sitting is common. Furthermore, this could serve as substantial evidence for providing specific home BP measurement guidelines to patients who adhere to a floor-sitting lifestyle.

Prediction of In-Hospital Mortality for Ischemic Cardiogenic Shock Requiring Venoarterial Extracorporeal Membrane Oxygenation.

BACKGROUND: Clinical outcome of ischemic cardiogenic shock (CS) requiring extracorporeal membrane oxygenation is highly variable, necessitating appropriate assessment of prognosis. However, a systemic predictive model estimating the mortality of refractory ischemic CS is lacking. The PRECISE (Prediction of In-Hospital Mortality for Patients With Refractory Ischemic Cardiogenic Shock Requiring Veno-Arterial Extracorporeal Membrane Oxygenation Support) score was developed to predict the prognosis of refractory ischemic CS due to acute myocardial infarction. METHODS AND RESULTS: Data were obtained from the multicenter CS registry RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Device for Korean Patients With Cardiogenic Shock) that consists of 322 patients with acute myocardial infarction complicated by refractory ischemic CS requiring extracorporeal membrane oxygenation support. Fifteen parameters were selected to assess in-hospital mortality. The developed model was validated internally and externally using an independent external cohort (n=138). Among 322 patients, 138 (42.9%) survived postdischarge. Fifteen predictors were included for model development: age, diastolic blood pressure, hypertension, chronic kidney disease, peak lactic acid, serum creatinine, lowest left ventricular ejection fraction, vasoactive inotropic score, shock to extracorporeal membrane oxygenation insertion time, extracorporeal cardiopulmonary resuscitation, use of intra-aortic balloon pump, continuous renal replacement therapy, mechanical ventilator, successful coronary revascularization, and staged percutaneous coronary intervention. The PRECISE score yielded a high area under the receiver-operating characteristic curve (0.894 [95% CI, 0.860-0.927]). External validation and calibration resulted in competent sensitivity (area under the receiver-operating characteristic curve, 0.895 [95% CI, 0.853-0.930]). CONCLUSIONS: The PRECISE score demonstrated high predictive performance and directly translates into the expected in-hospital mortality rate. The PRECISE score may be used to support clinical decision-making in ischemic CS (www.theprecisescore.com). REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02985008.

Predictors of in-hospital mortality after successful weaning of venoarterial extracorporeal membrane oxygenation in cardiogenic shock.

Limited knowledge exists regarding the predictors of mortality after successful weaning of venoarterial extracorporeal membrane oxygenation (ECMO). We aimed to identify predictors of in-hospital mortality in patients with cardiogenic shock (CS) after successful weaning from ECMO. Data were obtained from a multicenter registry of CS. Successful ECMO weaning was defined as survival with minimal mean arterial pressure (> 65 mmHg) for > 24 h after ECMO removal. The primary outcome was in-hospital mortality after successful ECMO weaning. Among 1247 patients with CS, 485 received ECMO, and 262 were successfully weaned from ECMO. In-hospital mortality occurred in 48 patients (18.3%). Survivors at discharge differed significantly from non-survivors in age, cardiovascular comorbidities, cause of CS, left ventricular ejection fraction, and use of adjunctive therapy. Five independent predictors for in-hospital mortality were identified: use of continuous renal replacement therapy (odds ratio 5.429, 95% confidence interval [CI] 2.468-11.940; p < 0.001), use of intra-aortic balloon pump (3.204, 1.105-9.287; p = 0.032), diabetes mellitus (3.152, 1.414-7.023; p = 0.005), age (1.050, 1.016-1.084; p = 0.003), and left ventricular ejection fraction after ECMO insertion (0.957, 0.927-0.987; p = 0.006). Even after successful weaning of ECMO, patients with irreversible risk factors should be recognized, and careful monitoring should be done for sign of deconditioning.

Effect of Cilostazol on Patients With Diabetes Who Underwent Endovascular Treatment for Peripheral Artery Disease.

Background No large-scale study has compared the clinical impact of triple antiplatelet therapy (TAPT: aspirin, clopidogrel, and cilostazol) and dual antiplatelet therapy (DAPT) on adverse limb events in patients with diabetes after endovascular therapy (EVT) for peripheral artery disease. Thus, we investigate the effect of cilostazol added to a DAPT on the clinical outcomes after EVT in patients with diabetes using a nationwide, multicenter, real-world registry. Methods and Results A total of 990 patients with diabetes who underwent EVT were enrolled from the retrospective cohorts of a Korean multicenter EVT registry and were divided according to the antiplatelet regimen (TAPT [n=350; 35.4%] versus DAPT [n=640; 64.6%]). After propensity score matching based on clinical characteristics, a total of 350 pairs were compared for clinical outcomes. The primary end points were major adverse limb events, a composite of major amputation, minor amputation, and reintervention. For the matched study groups, the lesion length was 125.4±102.0 mm, and severe calcification was observed in 47.4%. The technical success rate (96.9% versus 94.0%; P=0.102) and the complication rate (6.9% versus 6.6%; P>0.999) were similar between the TAPT and DAPT groups. At 2-year follow-up, the incidence of major adverse limb events (16.6% versus 19.4%; P=0.260) did not differ between the 2 groups. However, the TAPT group showed less minor amputation than the DAPT group (2.0% versus 6.3%; P=0.004). In multivariate analysis, TAPT was an independent predictor of minor amputation (adjusted hazard ratio, 0.354 [95% CI, 0.158-0.794]; P=0.012). Conclusions In patients with diabetes undergoing EVT for peripheral artery disease, TAPT did not decrease the incidence of major adverse limb events but may be associated with a decreased risk of minor amputation.

Comparison of neoatherosclerosis and a clinical outcomes between bioabsorbable versus durable polymer drug-eluting stent: Verification by optical coherence tomography analysis.

BACKGROUND: Neoatherosclerosis after drug-eluting stent (DES) implantation is known to be related with increased risk of late restenosis and stent thrombosis. Neoatherosclerosis and relevant clinical outcomes between bioabsorbable polymer DES (BP-DES) and second-generation durable polymer DES (DP-DES) were evaluated by optical coherence tomography (OCT) analysis. METHODS: A total of 311 patients (319 lesions) undergoing OCT analysis after DES implantation were enrolled and divided into two groups according to stent type (BP-DES [150 patients, 153 lesions] and DP-DES [161 patients, 166 lesions]). Follow-up OCT analysis was performed at least 9 months after index stent implantation. Neoatherosclerosis was defined as presence of thin-cap fibroatheroma, calcified plaque, and lipid plaque. Primary endpoint was the incidence of neoatherosclerosis, and the secondary endpoints were the occurrence of major adverse cardiac events (MACE), defined as a composite of death, myocardial infarction, target lesion revascularization, or stent thrombosis and to find independent predictors of neoatherosclerosis. RESULTS: The incidence of neoatherosclerosis was lower in the BP-DES group than the DP-DES group (5.2% vs. 14.5%, p = 0.008), which was driven by lipid plaque. However, the incidence of MACE did not show statistical difference between the two groups in median 4-year follow-up (3.3% vs. 7.8%, hazard ratio 1.964, 95% confidence interval 0.688-5.611, p = 0.207). Less use of angiotensin converting enzyme inhibitors/angiotensin II receptor blockade and higher degree of neointimal hyperplasia remained independent predictors of neoatherosclerosis on Cox regression analysis. CONCLUSIONS: Patients undergoing BP-DES implantation had lower incidence of neoatherosclerosis than DP-DES, which did not reach statistically better clinical outcomes.

Influence of concomitant percutaneous transluminal angioplasty with percutaneous coronary intervention on clinical outcomes of stable lower extremity artery diseases.

Concomitant percutaneous transluminal angioplasty (PTA) at the time of percutaneous coronary intervention (PCI) is often performed because lower extremity artery disease (LEAD) commonly coincides with coronary artery disease. We investigated the impact of concomitant PTA on both cardiovascular and limb outcomes in the Korean National Health Insurance Service registry. Among 78,185 patients undergoing PCI, 6563 patients with stable LEAD without limb ischemia were included. After 1:5 propensity score matching was conducted, 279 patients in the PTA + PCI group and 1385 patients in the PCI group were compared. Multivariate Cox proportional hazard models showed that the risk of all-cause death was higher in the PTA + PCI group than in the PCI group, whereas the risks of myocardial infarction, repeat revascularization, stroke, cardiovascular death and bleeding events were not different between the 2 groups. In contrast, the risks of end-stage renal disease and unfavorable limb outcomes were higher in the PTA + PCI group. Mediation analyses revealed that amputation and PTA after discharge significantly mediated the association between concomitant PTA and all-cause death. Concomitant PTA was not associated with an increased risk of cardiovascular events but may increase the risk of all-cause death mediated by unfavorable renal and limb outcomes in patients with stable LEAD.

Association between Age of Onset of Hypertension and Incident Atrial Fibrillation.

We investigated whether age at hypertension (HTN) onset was associated with the risk of atrial fibrillation (AF) in the general population. This prospective longitudinal community-based cohort study included 9892 participants without AF at baseline, who underwent biennial electrocardiography for a median duration of 11.5 years. The participants were divided into five groups, consisting of a normotensive group (Group-N) and four HTN groups based on HTN onset age: <45 years (Group-H1); 45−54 years (Group-H2); 55−64 years (Group-H3); and ≥65 years (Group-H4). A multivariate Cox proportional hazards model showed that the presence of HTN at baseline was associated with higher AF risk (hazard ratio [HR], 1.93; 95% confidence interval [CI] 1.32−2.80). The participants in Group-H1 had the highest risk of AF (HR 3.18; CI 1.74−5.82), and the risk of AF decreased as HTN onset age increased across the four HTN groups (p for trend = 0.014). The AF onset age was significantly younger in participants in Group-H1 than in Groups-H2−H4. Early-onset HTN was associated with an increased risk of AF, and younger onset of AF in the general population. Surveillance for AF should be considered at a younger age in individuals with HTN.

Efficacy and Safety of SID142 in Patients With Peripheral Arterial Disease: A Multicenter, Randomized, Double-Blind, Active-Controlled, Parallel-Group, Phase III Clinical Trial.

PURPOSE: Renexin® is a combination pill of cilostazol and Ginkgo biloba leaf extract that is used for the improvement of ischemic symptoms associated with peripheral arterial disease (PAD). SID142 is a controlled-release tablet of cilostazol (200 mg) and G biloba leaf extract (160 mg) that was developed to address the limitation of BID administration with Renexin. This study aimed to verify that SID142 was not inferior to Renexin in the treatment of patients with PAD. METHODS: This was a multicenter, randomized, double-blind, active-controlled, parallel-group, Phase III clinical trial. Study subjects were randomized to receive SID142 once daily or Renexin twice a day for 12 weeks. The primary end point was a change in the patient assessment of lower leg pain intensity with the use of a visual analog scale (VAS) after 12 weeks of treatment. If the lower limit of the two-sided 95% CI was greater than -10, the study drug was declared noninferior to the reference drug. Secondary efficacy end points included cold sensation, ankle-brachial index, ankle systolic pressure, maximum walking distance, pain-free walking distance, and investigator's global assessment. Study group results were compared 4, 8, and 12 weeks after treatment. Adverse events were assessed as a safety end point. FINDINGS: In total, 344 subjects from 19 medical centers were screened, and a total of 170 subjects were randomly assigned to either the SID142 (n = 86) or the Renexin (n = 84) group. Analysis of the change in lower extremity pain at 12 weeks compared with baseline revealed that SID142 was not inferior to Renexin (21.44 [19.23] vs 22.30 [17.75]; 95% CI, -7.70 to 5.97; P = 0.5942). No significant differences were found between groups in any secondary efficacy end point. However, the incidence of adverse reactions was significantly lower in the SID142 group (22.35% vs 39.29%; P = 0.0171). IMPLICATIONS: SID142 once daily was not inferior to Renexin twice a day for efficacy in patients with PAD. SID142 had a favorable safety profile. CLINICALTRIALS: gov identifier: NCT03318276.

Impact of carotid atherosclerosis in CHA2DS2-VASc-based risk score on predicting ischemic stroke in patients with atrial fibrillation.

BACKGROUND/AIMS: Vascular disease is an established risk factor for stroke in patients with atrial fibrillation (AF), which is included in CHA2DS2-VASc score. However, the role of carotid atherosclerosis remains to be determined. METHODS: Three hundred-ten patients with AF who underwent carotid sonography were enrolled. RESULTS: During a median follow-up of 31 months, 18 events (5.8%) of stroke were identified. Patients with stroke had higher carotid intima-media thickness (CIMT) (1.16 ± 0.33 mm vs. 0.98 ± 0.25 mm, p = 0.017). CIMT was significantly increased according to the CHA2DS2-VASc score (p < 0.001) and it was correlated with left ventricular mass index and early diastolic mitral annular velocity (e'), a ratio of early transmitral flow velocity to e' (E/e') and pulmonary artery systolic pressure (all p < 0.05). Cox regression using multivariate models showed that carotid plaque was associated with the risk of stroke (hazard ratio, 3.748; 95% confidence interval [CI], 1.107 to 12.688; p = 0.034). C-statistics increased from 0.648 (95% CI, 0.538 to 0.757) to 0.716 (95% CI, 0.628 to 0.804) in the CHA2DS2-VASc score model after the addition of CIMT and carotid plaque as a vascular component (p = 0.013). CONCLUSION: Increased CIMT and presence of carotid plaque are associated with a high risk of ischemic stroke, and CIMT is related to myocardial remodeling and diastolic dysfunction, suggesting that carotid atherosclerosis can improve risk prediction of stroke in patients with AF, when included under vascular disease in the CHA2DS2-VASc scoring system.

Comparison of clinical outcomes between multiple antithrombotic therapy versus left atrial appendage occlusion with dual antiplatelet therapy in patients with atrial fibrillation undergoing drug-eluting stent implantation.

BACKGROUND: Complex antithrombotic regimens are recommended for patients with atrial fibrillation (AF) undergoing drug-eluting stent (DES) implantation but carry high bleeding risk. HYPOTHESIS: We aimed to evaluate whether left atrial appendage occlusion (LAAO) with dual antiplatelet therapy (DAPT) improve clinical outcomes when compared with multiple antithrombotic therapy (MAT) in patients with AF undergoing DES implantation. METHODS: Among 475 AF patients who underwent DES, 41 patients treated by LAAO with DAPT and 434 patients on MAT were compared. MAT was defined as any combination of warfarin-based antithrombotic therapy. Among the MAT group, 34.8% were on triple antithrombotic therapy. The primary endpoint was a net adverse clinical event (NACE), a composite of cerebrovascular accident (CVA) and major bleeding. Secondary endpoints were CVA, major bleeding, major adverse cardiac and cerebral event (MACCE), MI, cardiovascular death, and all-cause death. Additional analysis between the new oral anticoagulant (NOAC)-based antithrombotic therapy group (n = 45) and the LAAO group was performed for the same endpoints. To adjust the confounding factors, inverse probability of treatment weighting (IPTW) was applied during the endpoint analysis. RESULTS: The LAAO group showed higher incidences of diabetes mellitus, prior CVA, higher CHA2DS2-VASc score (4.56±1.55 vs. 2.96±1.60; P<0.0001), and higher HAS-BLED score (3.24±1.20 vs. 2.13±0.75; P<0.0001). NACE occurred less frequently in the LAAO group than the MAT group at 24 months (9.4% vs. 15.3%; hazard ratio 0.274; 95% confidence interval 0.136 - 0.553; P = 0.0003), mainly driven by the reduction in major bleeding (2.4% vs. 9.3%; hazard ratio 0.119; 95% confidence interval 0.032 - 0.438; P = 0.001). The LAAO group with greater thrombotic and hemorrhagic risks showed comparable primary/secondary outcomes with the NOAC-based anti-thrombotic therapy group. CONCLUSIONS: Among patients with AF who underwent DES implantation, the LAAO group had better net clinical outcomes for preventing CVA and major bleeding than the MAT group. Further large-scale trials including comparisons with NOACs are warranted.

Effects of deferred versus immediate stenting on left ventricular function in patients with ST elevation myocardial infarction.

BACKGROUND: Previous studies have shown conflicting results on the benefits of deferred stenting (DS) in infarct size and the incidence of microvascular obstruction in patients with ST elevation myocardial infarction (STEMI). However, effect of DS on left ventricular (LV) function was not known. We aimed to evaluate whether DS improve LV function and relevant clinical outcomes after STEMI, using follow-up data from the INNOVATION study (NCT02324348). METHODS: In total, 114 patients were randomly assigned to DS group or immediate stenting (IS) group at a 1:1 ratio. LV functional remodeling indices and MACE (major adverse cardiac events: a composite of death, non-fatal MI, unplanned target vessel revascularization, or hospitalization due to heart failure) were compared between DS and IS groups. RESULTS: Serial echocardiographic analyses were completed in 89 subjects (78%). There were no significant changes in LV volume in either group. While LV ejection fraction and wall motion score index (WMSI) improved in both groups during follow-up, the increments were not statistically different between the 2 groups (4.3 ±â€Š8.2 vs 3.2 ±â€Š7.1, P = .504 for ΔLV ejection fraction; -0.16 ±â€Š0.25 vs -0.16 ±â€Š0.25, P = .99 for ΔWMSI). However, E/e'' was decreased and e' was increased only in the DS group (-3.31 ±â€Š5.60 vs -0.46 ±â€Š3.10, P = .005 for ΔE/e'; 0.77 ±â€Š1.71 vs -0.22 ±â€Š1.64, P = .009 for Δe'). The incidence of major adverse cardiac events was numerically lower in the DS group than in the IS group without a statistical significance at 1-year follow-up. CONCLUSIONS: Routine DS improved LV diastolic function but not systolic function compared with IS in patients with STEMI.