Optimal antithrombotic strategy in patients with atrial fibrillation beyond 1 year after drug-eluting stent implantation: Design and rationale of the randomized ADAPT AF-DES trial.

BACKGROUND: Both anticoagulation and antiplatelet therapies are recommended after percutaneous coronary intervention (PCI) in patients with atrial fibrillation (AF). Although contemporary guidelines recommend discontinuation of antiplatelet therapy 1 year after drug-eluting stent (DES) implantation due to excessive bleeding risk, supporting randomized trials are still lacking. METHODS: The ADAPT AF-DES trial is a multicenter, prospective, open-label, randomized, non-inferiority trial, enrolling 960 patients with AF with a CHA2DS2-VASc score > 1, who underwent PCI with DES implantation at least 12 months before enrollment. Eligible patients are randomly assigned to receive either non-vitamin K antagonist oral anticoagulant (NOAC) monotherapy or NOAC plus clopidogrel combination therapy. The primary outcome is net adverse clinical event (NACE) at 1 year after randomization, defined as a composite of all-cause death, myocardial infarction, stent thrombosis, stroke, systemic embolism, and major or clinically relevant non-major bleeding, as defined by the International Society on Thrombosis and Hemostasis criteria. We hypothesize that NOAC monotherapy would be non-inferior to NOAC plus clopidogrel combination therapy for NACE in patients with AF beyond 12 months after DES implantation. CONCLUSIONS: The ADAPT AF-DES trial will evaluate the efficacy and safety of NOAC monotherapy versus NOAC plus clopidogrel combination therapy in patients with AF beyond 12 months after PCI with DES implantation. The ADAPT AF-DES trial will provide robust evidence for an optimal antithrombotic strategy in patients with AF after DES implantation. CLINICAL TRIAL REGISTRATION: https://www. CLINICALTRIALS: gov. Unique identifier: NCT04250116.

Transradial Versus Transfemoral Access for Bifurcation Percutaneous Coronary Intervention Using Second-Generation Drug-Eluting Stent.

BACKGROUND: The benefits of transradial access (TRA) over transfemoral access (TFA) for bifurcation percutaneous coronary intervention (PCI) are uncertain because of the limited availability of device selection. This study aimed to compare the procedural differences and the in-hospital and long-term outcomes of TRA and TFA for bifurcation PCI using second-generation drug-eluting stents (DESs). METHODS: Based on data from the Coronary Bifurcation Stenting Registry III, a retrospective registry of 2,648 patients undergoing bifurcation PCI with second-generation DES from 21 centers in South Korea, patients were categorized into the TRA group (n = 1,507) or the TFA group (n = 1,141). After propensity score matching (PSM), procedural differences, in-hospital outcomes, and device-oriented composite outcomes (DOCOs; a composite of cardiac death, target vessel-related myocardial infarction, and target lesion revascularization) were compared between the two groups (772 matched patients each group). RESULTS: Despite well-balanced baseline clinical and lesion characteristics after PSM, the use of the two-stent strategy (14.2% vs. 23.7%, P = 0.001) and the incidence of in-hospital adverse outcomes, primarily driven by access site complications (2.2% vs. 4.4%, P = 0.015), were significantly lower in the TRA group than in the TFA group. At the 5-year follow-up, the incidence of DOCOs was similar between the groups (6.3% vs. 7.1%, P = 0.639). CONCLUSION: The findings suggested that TRA may be safer than TFA for bifurcation PCI using second-generation DESs. Despite differences in treatment strategy, TRA was associated with similar long-term clinical outcomes as those of TFA. Therefore, TRA might be the preferred access for bifurcation PCI using second-generation DES. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03068494.

Long-term efficacy and safety of moderate-intensity statin with ezetimibe combination therapy versus high-intensity statin monotherapy in patients with atherosclerotic cardiovascular disease (RACING): a randomised, open-label, non-inferiority trial.

BACKGROUND: Drug combinations rather than increasing doses of one drug can achieve greater efficacy and lower risks. Thus, as an alternative to high-intensity statin monotherapy, moderate-intensity statin with ezetimibe combination therapy can lower LDL cholesterol concentrations effectively while reducing adverse effects. However, evidence from randomised trials to compare long-term clinical outcomes is needed. METHODS: In this randomised, open-label, non-inferiority trial, patients with atherosclerotic cardiovascular disease (ASCVD) at 26 clinical centres in South Korea were randomly assigned (1:1) to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 10 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg). The primary endpoint was the 3-year composite of cardiovascular death, major cardiovascular events, or non-fatal stroke, in the intention-to-treat population with a non-inferiority margin of 2·0%. This trial is registered with ClinicalTrials.gov, NCT03044665 and is complete. FINDINGS: Between Feb 14, 2017, and Dec 18, 2018, 3780 patients were enrolled: 1894 patients to the combination therapy group and 1886 to the high-intensity statin monotherapy group. The primary endpoint occurred in 172 patients (9·1%) in the combination therapy group and 186 patients (9·9%) in the high-intensity statin monotherapy group (absolute difference -0·78%; 90% CI -2·39 to 0·83). LDL cholesterol concentrations of less than 70 mg/dL at 1, 2, and 3 years were observed in 73%, 75%, and 72% of patients in the combination therapy group, and 55%, 60%, and 58% of patients in the high-intensity statin monotherapy group (all p<0·0001). Discontinuation or dose reduction of the study drug by intolerance was observed in 88 patients (4·8%) and 150 patients (8·2%), respectively (p<0·0001). INTERPRETATION: Among patients with ASCVD, moderate-intensity statin with ezetimibe combination therapy was non-inferior to high-intensity statin monotherapy for the 3-year composite outcomes with a higher proportion of patients with LDL cholesterol concentrations of less than 70 mg/dL and lower intolerance-related drug discontinuation or dose reduction. FUNDING: Hanmi Pharmaceutical.

Long-Term Clinical Outcomes and Its Predictors Between the 1- and 2-Stent Strategy in Coronary Bifurcation Lesions　- A Baseline Clinical and Lesion Characteristic-Matched Analysis.

BACKGROUND: Differences in the impact of the 1- or 2-stent strategy in similar coronary bifurcation lesion conditions are not well understood. This study investigated the clinical outcomes and its predictors between 1 or 2 stents in propensity score-matched (PSM) complex bifurcation lesions.Methods and Results: We analyzed the data of patients with bifurcation lesions, obtained from a multicenter registry of 2,648 patients (median follow up, 53 months). The patients were treated by second generation drug-eluting stents (DESs). The primary outcome was target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TVMI), and ischemia-driven target lesion revascularization (TLR). PSM was performed to balance baseline clinical and angiographic discrepancies between 1 and 2 stents. After PSM (N=333 from each group), the 2-stent group had more TLRs (hazard ratio [HR] 3.14, 95% confidence interval [CI] 1.42-6.97, P=0.005) and fewer hard endpoints (composite of cardiac death and TVMI; HR 0.44, 95% CI 0.19-1.01, P=0.054), which resulted in a similar TLF rate (HR 1.40, 95% CI 0.83-2.37, P=0.209) compared to the 1-stent group. Compared with 1-stent, the 2-stent technique was more frequently associated with less TLF in the presence of main vessel (pinteraction=0.008) and side branch calcification (pinteraction=0.010). CONCLUSIONS: The 2-stent strategy should be considered to reduce hard clinical endpoints in complex bifurcation lesions, particularly those with calcifications.

Comparison of 2-Stenting Strategies Depending on Sequence or Technique for Bifurcation Lesions in the Second-Generation Drug-Eluting Stent Era　- Analysis From the COBIS (Coronary Bifurcation Stenting) III Registry.

BACKGROUND: It has not been determined which specific 2-stenting strategy is the best for bifurcation lesions. Our aim was to investigate the clinical outcomes of various 2-stenting strategies in the era of 2nd-generation drug-eluting stents (2G-DES).Methods and Results:We analyzed 454 patients who finally underwent 2-stenting for a bifurcation lesion, from among 2,648 patients enrolled in the COBIS III registry. The primary outcome was target lesion failure (TLF). Patients were analyzed according to stenting sequence (provisional [main vessel stenting first] vs. systemic [side branch stenting first]) and stenting technique (crush vs. T vs. culotte vs. kissing/V stenting). Overall, 4.4 years' TLF after 2-stenting treatment for bifurcation lesion was excellent: TLF 11.2% and stent thrombosis 1.3%. There was no difference in TLF according to 2-stenting strategy (11.1% vs. 10.5%, P=0.990 for provisional and systemic sequence; 8.6% vs. 14.4% vs. 12.9% vs. 12.2%, P=0.326 for crush, T, culotte, kissing/V technique, respectively). Only left main (LM) disease and a shorter duration of dual antiplatelet therapy (DAPT) were associated with TLF. The distribution of DAPT duration differed between patients with and without TLF, and the time-point of intersection was 2.5 years. Also, the side branch was the most common site of restenosis. CONCLUSIONS: The stenting sequence or technique did not affect clinical outcomes, but LM disease and shorter DAPT were associated with TLF, in patients with bifurcation lesions undergoing 2-stenting with 2G-DES.

Impact of duration and dosage of statin treatment and epicardial fat thickness on the recurrence of atrial fibrillation after electrical cardioversion.

The purpose of this study was to investigate the time-dependent effect of statin treatment and echocardiographic epicardial fat thickness (EFT) on the maintenance of sinus rhythm (SR) in atrial fibrillation (AF) patients after electrical cardioversion (EC). One hundred sixty-three AF patients without previous statin treatment who underwent EC were consecutively enrolled. The maintenance rate of SR after EC (1, 3, 6, and 12 months) as documented by electrocardiogram and EFT were compared between patients with statin treatment (statin group, n = 63) and those without (no statin group, n = 100). There was no significant difference in the maintenance rate of SR between the groups soon after EC (statin group; 85.7 % vs. no statin; 84.8%, p = 0.535), after 1 month (71.0 vs. 59.1%, p = 0.091), and after 3 months (63.2 vs. 50.0%, p = 0.086). However, the maintenance rate of SR was significantly higher in the statin group compared to no statin group (61.8 vs. 42.9%, p = 0.024) after 6 months, and this significant difference persisted up to 12 months of follow up (60.1 vs. 36.4%, p = 0.001). Patients with recurrence showed higher baseline EFT (7.4 ± 2.7 vs. 8.5 ± 3.0 mm, p = 0.014). Multivariate linear regression analysis indicated that EFT, left atrial diameter, high-density lipoprotein cholesterol, statin treatment, and dose were the significant contributors to the maintenance of SR for all periods after EC. Statin treatment and low EFT were associated with a higher maintenance rate of SR in AF patients after EC. Significant benefit of statin was realized 6 months after EC, and this benefit was shown to be maintained over time.

Determinants of high cardiovascular risk in relation to plaque-composition of a non-culprit coronary segment visualized by near-infrared spectroscopy in patients undergoing percutaneous coronary intervention.

AIM: The aim of this study was to determine the relationship between clinical and blood characteristics of a vascular inflammatory milieu and coronary plaque composition visualized by near-infrared spectroscopy (NIRS) in percutaneous coronary intervention (PCI) patients. METHODS AND RESULTS: Between April 2009 and January 2011, we performed NIRS in 208 patients who underwent PCI or invasive diagnostic coronary exploration for various indications. Imaging was performed of one non-intervened coronary segment after the initial procedure. Univariate and multivariate linear regression analyses were applied to evaluate the relationship between the acquired NIRS-derived lipid core burden index (LCBI) and clinical and blood (lipids and hs-C-reactive protein) characteristics. Patients with a history of hypercholesterolaemia [median 48 (inter-quartile range 21-101) vs. 38 (13-70), P = 0.043] and multi-vessel disease [55 (24-104) vs. 32 (12-71), P = 0.012] had higher LCBI levels. Men had higher LCBI than women [48 (21-95) vs. 27 (9-59), P = 0.003]. Hypercholesterolaemia and gender remained significant in multivariate regression analysis, whereas also a history of non-cardiac vascular disease and beta-blockers were positively associated with LCBI. Altogether 23.2% of the variability in LCBI could be explained by clinical and blood characteristics. CONCLUSION: Clinical characteristics reflecting patients with a high cardiovascular risk profile explained 23.2% of the variability in LCBI, whereas blood biomarkers added little. Further research is warranted to evaluate whether NIRS has the potential to provide additional prognostic information about patients' cardiovascular risk.

In vivo detection of high-risk coronary plaques by radiofrequency intravascular ultrasound and cardiovascular outcome: results of the ATHEROREMO-IVUS study.

AIMS: Acute coronary syndromes (ACS) are mostly caused by plaque rupture. This study aims to investigate the prognostic value of in vivo detection of high-risk coronary plaques by intravascular ultrasound (IVUS) in patients undergoing coronary angiography. METHODS AND RESULTS: Between November 2008 and January 2011, IVUS of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for ACS (n = 318) or stable angina (n = 263). Primary endpoint was major adverse cardiac events (MACEs) defined as mortality, ACS, or unplanned coronary revascularization. Culprit lesion-related events were not counted. Cumulative Kaplan-Meier incidence of 1-year MACE was 7.8%. The presence of IVUS virtual histology-derived thin-cap fibroatheroma (TCFA) lesions (present 10.8% vs. absent 5.6%; adjusted HR: 1.98, 95% CI: 1.09-3.60; P = 0.026) and lesions with a plaque burden of ≥70% (present 16.2% vs. absent 5.5%; adjusted HR: 2.90, 95% CI: 1.60-5.25; P < 0.001) were independently associated with a higher MACE rate. Thin-cap fibroatheroma lesions were also independently associated with the composite of death or ACS only (present 7.5% vs. absent 3.0%; adjusted HR: 2.51, 95% CI: 1.15-5.49; P = 0.021). Thin-cap fibroatheroma lesions with a plaque burden of ≥70% were associated with a higher MACE rate within (P = 0.011) and after (P < 0.001) 6 months of follow-up, while smaller TCFA lesions were only associated with a higher MACE rate after 6 months (P = 0.033). CONCLUSION: In patients undergoing coronary angiography, the presence of IVUS virtual histology-derived TCFA lesions in a non-culprit coronary artery is strongly and independently predictive for the occurrence of MACE within 1 year, particularly of death and ACS. Thin-cap fibroatheroma lesions with a large plaque burden carry higher risk than small TCFA lesions, especially on the short term.

Reproducibility of intravascular ultrasound iMAP for radiofrequency data analysis: implications for design of longitudinal studies.

BACKGROUND: iMAP is a new intravascular ultrasound (IVUS) derived technique for tissue characterization using spectral analysis. Since there is a need for reproducibility data to design longitudinal studies, we sought to assess the in vivo reproducibility of this imaging technique. METHODS: iMAP (40 MHz, Boston Scientific Corporation) was performed in patients referred for elective percutaneous intervention and in whom a nonintervened vessel was judged suitable for a safe IVUS analysis. Overall 20 patients with 20 non-angiographically significant lesions were assessed by two independent observers. Five of these 20 patients received an additional iMAP analysis using a new IVUS catheter and using the same catheter after its engagement and reengagement. RESULTS: The interobserver relative difference in plaque area was 2.5%. Limits of agreement for lumen, vessel, and plaque area measurements were 1.62, -2.47 mm(2) ; 2.09, -3.71 mm(2) ; 2.80, -3.72 mm(2) ; respectively. Limits of agreement for fibrotic, lipidic, necrotic, and calcified measurements were 1.32, -1.44 mm(2) ; 0.24, -0.36 mm(2) ; 1.50, -2.26 mm(2) ; 0.09, -0.11 mm(2) ; respectively. The intercatheter and intracatheter relative difference in plaque area were 0.9% and 4.1%, respectively. Although the variability for compositional measurements increased using two different catheters or using the same catheter twice, the variability for compositional measurements keeps always below 10%. CONCLUSIONS: Our analysis demonstrates that the geometrical and compositional iMAP analysis is acceptably reproducible.

Simvastatin attenuates the oxidative stress, endothelial thrombogenicity and the inducibility of atrial fibrillation in a rat model of ischemic heart failure.

Increased atrial oxidative stress has an important role in inducing and maintaining atrial fibrillation (AF), and the activation of the small GTPase Rac1 contributes to the oxidative stress. We investigated the relationship of Rac1, atrial endothelial thromboprotective markers and AF inducibility and if simvastatin has a potential beneficial effect on a myocardial infarction (MI)-induced heart failure (HF) rat model. Rats were randomized into three groups (shams, MI group and simvastatin treatment group) and underwent echocardiography, AF induction studies and left atrial (LA) fibrosis analysis. Atrial Rac 1, sodium calcium exchanger (INCX), sarcoplasmic reticulum calcium ATPase (SERCA), endothelial nitric oxide synthase (eNOS) and induced nitric oxide synthase (iNOS) were measured. AF inducibility, AF duration and LA fibrosis were significantly higher in the MI group (p < 0.001 vs. sham), which were significantly reduced by simvastatin (p < 0.05 vs. MI). The reduced expressions of atrial eNOS, SERCA, thrombomodulin, tissue factor pathway inhibitor and tissue plasminogen activator in the MI group were significantly improved by simvastatin. Furthermore, the increased expression of atrial iNOS, INCX and Rac1 activity were significantly decreased by the simvastatin. Oxidative stress, endothelial dysfunction and thrombogenicity are associated with the promotion of AF in a rat model of ischemic HF. These were associated with increased Rac1 activity, and simvastatin treatment prevents these changes.

Pre- and post-hemodialysis differences in heart failure diagnosis by current heart failure guidelines in patients with end-stage renal disease.

BACKGROUND: Patients with end-stage renal disease (ESRD) who are on hemodialysis (HD) have reduced vascular compliance and are likely to develop heart failure (HF). In this study, we estimated the prevalence of HF pre- and post-HD in ESRD using the current guidelines. METHODS: We prospectively investigated HF in ESRD patients on HD using echocardiography pre- and post-HD. We used the structural and functional abnormality criteria of the 2021 European Society of Cardiology guidelines. RESULTS: A total of 54 patients were enrolled. The mean age was 62.6 years, and 40.1% were male. Forty-five patients (83.3%) had hypertension, 28 (51.9%) had diabetes, and 20 (37.0%) had ischemic heart disease. The mean N-terminal-pro brain natriuretic peptide BNP (NT-proBNP) level was 12,388.8 ± 2,592.2 pg/dL. The mean ideal body weight was 59.3 kg, mean hemodialysis time was 237.4 min, and mean real filtration was 2.8 kg. The mean left ventricular ejection fraction (LVEF) was 62.4%, and mean left ventricular end-diastolic diameter was 52.0 mm in pre-HD. Post-HD echocardiography showed significantly lower left atrial volume index (33.3 ± 15.9 vs. 40.6 ± 17.1, p = 0.030), tricuspid regurgitation jet V (2.5 ± 0.4 vs. 2.8 ± 0.4 m/s, p < 0.001), and right ventricular systolic pressure (32.1 ± 10.3 vs. 38.4 ± 11.6, p = 0.005) compared with pre-HD. There were no differences in LVEF, E/E' ratio, or left ventricular global longitudinal strain. A total of 88.9% of pre-HD patients and 66.7% of post-HD patients had either structural or functional abnormalities in echocardiographic parameters according to recent HF guidelines (p = 0.007). CONCLUSIONS: Our data showed that the majority of patients undergoing hemodialysis satisfy the diagnostic criteria for HF according to current HF guidelines. Pre-HD patients had a 22.2% higher incidence in the prevalence of functional or structural abnormalities as compared with post-HD patients.

Hemodialysis Efficiency Predictor in End-Stage Kidney Disease Using Real-Time Heart Rate Variability.

BACKGROUND: Autonomic dysfunction as a long-term complication may occur in end-stage kidney disease (ESKD) patients and can be diagnosed using heart rate variability (HRV) analyzed from electrocardiogram (ECG) recordings. There is limited data about HRV using real-time ECG to predict hemodialysis (HD) efficiency in patients with ESKD who are routinely doing HD in the real world. METHODS: A total of 50 patients (62.1 ± 10.7 years) with ESKD underwent continuous real-time ECG monitoring (237.4 ± 15.3 min) during HD for HRV using remote monitoring system. Their electrolyte levels were checked before and after HD. We compared HRV according to electrolyte levels. RESULTS: During the monitor, we checked the ECG and electrolyte levels simultaneously a total of 2374 times for all of the patients. Both time and frequency domain HRV were higher when the patients had lower K+ level (<0.5 mEq/L) and P+ level change (<2 mEq/L) before and after HD as compared to those with a higher K+ level (≥0.5 mEq/L) and P+ level change (≥2 mEq/L). Additionally, patients with lower K+ and P+ level change groups had higher incidences of arrhythmic events including atrial/ventricular premature complexes, despite no difference of mean heart rate (p < 0.001). CONCLUSIONS: Higher HRV was independently associated with a poorly controlled K+ and P+ level during HD in patients with ESKD. This is consistently evidenced by the independent association between higher HRV, K+ and P+ levels in real time, suggesting that low electrolyte changes before and after HD alone may cause cardiac autonomic dysfunction.

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).

Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: the ASPIRE (efficAcy and safety of aPixaban in rEal-world practice in Korean frail patients with atrial fibrillation) study.

Background: Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce. Objectives: We prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion. Methods: The multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose. Results: Of 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the "marginal zone," defined as age 75-80 years, weight 60-65 kg, and creatinine levels 1.2-1.5 mg/dL. Conclusions: In real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

Efficacy and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe in patients with dyslipidemia and hypertension: A randomized, double-blind, multicenter, therapeutic confirmatory, phase III clinical trial.

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles.

Assessment of plaque evolution in coronary bifurcations located beyond everolimus eluting scaffolds: serial intravascular ultrasound virtual histology study.

PURPOSE: To evaluate the atherosclerotic evolution in coronary bifurcations located proximally and distally to a bioresorbable scaffold. METHODS: Thirty bifurcations located >5 mm beyond the scaffolded segment, being investigated with serial intravascular ultrasound virtual histology (IVUS-VH) examinations, at baseline and 2-years, in patients enrolled in the ABSORB cohort B1 study were included in this analysis. In each bifurcation, the frames portraying the proximal rim, in-bifurcation, and distal rim of the ostium of the side branch were analyzed. The geometric parameters and plaque types were evaluated at baseline and 2-years follow-up. RESULTS: There were no significant differences in the geometrical parameters such as lumen, vessel and plaque areas as well as in the composition of the atheroma between baseline and 2-years follow-up.When we separately examined the bifurcations located proximally and distally to the scaffolded segment, no changes were found at the distal bifurcations, while at the proximal bifurcations there was a statistical significant decrease in the plaque burden (36.67 ± 13.33% at baseline vs. 35.06 ± 13.20% at 2 years follow-up, p = 0.04).Ten necrotic core rich plaques were found at baseline, of which 2 regressed to either fibrotic plaque or to intimal thickening at 2 years follow-up. The other 8 did not change. Disease progression was noted in 3 plaques (1 adaptive intimal thickening, 1 fibrotic and 1 fibrocalcific plaque) that evolved to necrotic rich plaques. CONCLUSIONS: Plaque regression was noted at the bifurcations located proximally to the bioresorbable scaffold but not at these located distally. Additional studies are required to confirm this finding and examine further the effect of drug elution on atherosclerotic evolution.

Left atrial responses to acute right ventricular apical pacing in patients with sick sinus syndrome.

Chronic right ventricular apical (RVA) pacing can lead to an increased risk of heart failure and atrial fibrillation, but the acute effects of RVA pacing on left atrial (LA) function are not well known. Twenty-four patients with sick sinus syndrome and intact intrinsic atrioventricular conduction were included. All patients received dual-chamber pacemaker implants with the atrial lead in the right atrial appendage and the ventricular lead in the right ventricular (RV) apex. Transthoracic standard and strain echocardiography (measured by tissue Doppler imaging and speckle tracking image) were performed to identify functional changes in the left ventricle (LV) and LA before and after 1 hour of RVA pacing. The LA volume index did not change after pacing; however, the ratio of peak early diastolic mitral flow velocity (E) to peak early diastolic mitral annular velocity (Ea) was significantly increased and peak systolic LA strain (Sm), mean peak systolic LA strain rate (SmSR), peak early diastolic LA strain rate (EmSR), and peak late diastolic LA strain rate (AmSR) were significantly reduced after RV pacing. LV dyssynchrony, induced by RV pacing, had a significant correlation with E/Ea, Sm, and SmSR after pacing. E/Ea also had a negative correlation with Sm and SmSR after pacing. Multivariate regression analysis identified LV dyssynchrony and E/Ea as important factors that affect Sm, SmSR, EmSR, and AmSR after acute RVA pacing. Acute RVA pacing results in LA functional change and LV dyssynchrony and higher LV filling pressures reflected by E/Ea are important causes of LA dysfunction after acute RVA pacing.

Endothelial-dependent vasomotion in a coronary segment treated by ABSORB everolimus-eluting bioresorbable vascular scaffold system is related to plaque composition at the time of bioresorption of the polymer: indirect finding of vascular reparative therapy?

AIMS: To analyse the vasoreactivity of a coronary segment, previously scaffolded by the ABSORB bioresorbable vascular scaffold (BVS) device, in relationship to its intravascular ultrasound-virtual histology (IVUS-VH) composition and reduction in greyscale echogenicity of the struts. Coronary segments, transiently scaffolded by a polymeric device, may in the long-term recover a normal vasomotor tone. Recovery of a normal endothelial-dependent vasomotion may be enabled by scaffold bioresorption, composition of the underlying tissue, or a combination of both mechanisms. METHODS AND RESULTS: All patients from the ABSORB Cohort A and B trials, who underwent a vasomotion test and IVUS-VH investigation at 12 and 24 months, were included. Acetylcholine (Ach) and nitroglycerin were used to test either the endothelial-dependent or -independent vasomotion of the treated segment. Changes in polymeric strut echogenicity-a surrogate for bioresorption-IVUS-VH composition of the tissue underneath the scaffold and their relationship with the pharmacologically induced vasomotion were all evaluated. Overall, 26 patients underwent the vasomotion test (18 at 12 and 8 at 24 months). Vasodilatory response to Ach was quantitatively associated with larger reductions over time in polymeric strut echogenicity (y= -0.159x- 6.85; r= -0.781, P< 0.001). Scaffolded segments with vasoconstriction to Ach had larger vessel areas (14.37 ± 2.50 vs. 11.85 ± 2.54 mm(2), P= 0.030), larger plaque burden (57.31 ± 5.96 vs. 49.09 ± 9.10%, P= 0.018), and larger necrotic core (NC) areas [1.39 (+1.14, +1.74) vs. 0.78 mm(2) (+0.20, +0.98), P= 0.006] compared with those with vasodilation. CONCLUSION: Vasodilatory response to Ach, in coronary segments scaffolded by the ABSORB BVS device, is associated with a reduction in echogenicity of the scaffold over time, and a low amount of NC. In particular, the latter finding resembles the behaviour of a native coronary artery not caged by an intracoronary device.

Effects of the beta-blocker carvedilol on arrhythmia and long-term clinical outcomes in benign prostate hypertrophy patients.

Benign prostatic hypertrophy (BPH) is associated with autonomic dysfunction and sympathetic nervous system mediated by the alpha receptor. However, limited data exist regarding the effects of the beta-blocker (BB) carvedilol on arrhythmia and urologic outcomes in BPH patients. Our database of patients diagnosed with BPH from 2015 to 2020 was used to obtain echocardiography and electrocardiogram data. Inclusion criteria were BPH patients taking BBs. International Prostate Symptom Score questionnaire were used to evaluate the urinary symptoms and quality of life. Among 448 patients with BPH (69.2 ± 10.9 years) taking BBs, 219 patients took carvedilol (48.9%) and 229 patients took a non-carvedilol BB (51.1%; bisoprolol, 184 patients, 80% or nebivolol, 45 patients, 20%). Difference in the baseline characteristics was not observed. During the median 36-month follow-up, a lower incidence of arrhythmic events (P = .029), total urologic events (P < .001), and less use of additive alpha-blocker was observed in the carvedilol group (P = .022). In multivariate analysis, less carvedilol use (P = .019), heart failure (P < .001), stroke (P < .001), and cardiomyopathy (P = .046) were independent risk factors for arrhythmic events. In addition, less carvedilol use (P = .009) and older age (P = .005) were independent risk factors for urologic events based on BB type at the median 36-month follow-up. The use of carvedilol was associated with less arrhythmic events in BPH patients with palpitation and decreased the incidence of urologic events in BPH compared with the use of non-carvedilol BBs in long-term follow-up.

Real-time heart rate variability according to ambulatory glucose profile in patients with diabetes mellitus.

Background: Autonomic neuropathy commonly occurs as a long-term complication of diabetes mellitus (DM) and can be diagnosed based on heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There are limited data on HRV using real-time ECG and ambulatory glucose monitoring in patients with DM. The aim of this study was to investigate real-time HRV according to ambulatory glucose levels in patients with DM. Methods: A total of 43 patients (66.3 ± 7.5 years) with DM underwent continuous real-time ECG monitoring (225.7 ± 107.3 h) for HRV and ambulatory glucose monitoring using a remote monitoring system. We compared the HRV according to the ambulatory glucose profile. Data were analyzed according to the target in glucose range (TIR). Results: There were no significant differences in the baseline characteristics of the patients according to the TIR. During monitoring, we checked ECG and ambulatory glucose levels (a total of 15,090 times) simultaneously for all patients. Both time- and frequency-domain HRVs were lower when the patients had poorly controlled glucose levels (TIR < 70%) compared with well controlled glucose levels (TIR > 70%). In addition, heart and respiratory rates increased with real-time glucose levels (P < 0.001). Conclusions: Poorly controlled glucose levels were independently associated with lower HRV in patients with DM. This was further substantiated by the independent continuous association between real-time measurements of hyperglycemia and lower HRV. These data strongly suggest that cardiac autonomic dysfunction is caused by elevated blood sugar levels.