Impact of Direct Measurement of Small Dense Low-Density Lipoprotein Cholesterol for Long-Term Secondary Prevention in Patients with Stable Coronary Artery Disease.

BACKGROUND: This study investigated whether directly measured small dense low-density lipoprotein cholesterol (D-sdLDL-C) can predict long-term coronary artery disease (CAD) events compared with low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (apoB), and estimated small dense low-density lipoprotein cholesterol (E-sdLDL-C) determined by the Sampson equation in patients with stable CAD. METHODS: D-sdLDL-C measured at Showa University between 2010 and 2022, and E-sdLDL-C were evaluated in 790 male and 244 female patients with stable CAD. CAD events, defined as sudden cardiac death, onset of acute coronary syndrome, and/or need for coronary revascularization, were monitored for 12 years. Cutoff lipid levels were determined by receiver operating characteristic curves. RESULTS: CAD events were observed in 238 male and 67 female patients. The Kaplan-Meier event-free survival curves showed that patients with D-sdLDL-C ≥32.1 mg/dL (0.83 mmol/L) had an increased risk for CAD events (P = 0.007), whereas risk in patients with E-sdLDL-C ≥36.2 mg/dL (0.94 mmol/L) was not increased. In the group with high D-sdLDL-C, the multivariable-adjusted hazard ratio (HR) was 1.47 (95% CI, 1.15-1.89), and it remained significant after adjustment for LDL-C, non-HDL-C, or apoB and in patients treated with statins. HRs for high LDL-C, non-HDL-C, or apoB were not statistically significant after adjustment for high D-sdLDL-C. Higher D-sdLDL-C was associated with enhanced risk of high LDL-C, non-HDL-C, and apoB (HR 1.73; 95% CI, 1.27-2.37). CONCLUSIONS: Higher D-sdLDL-C can predict long-term recurrence of CAD in stable CAD patients independently of apoB and non-HDL-C. D-sdLDL-C is an independent risk enhancer for secondary CAD prevention, whereas E-sdLDL-C is not.UMIN-CTR Clinical Trial Number: UMIN000027504.

Effect of Novel Stratified Lipid Risk by "LDL-Window" and Flow-Mediated Dilation on the Prognosis of Coronary Artery Disease Using the FMD-J Study A Data.

BACKGROUND: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index.Methods and Results: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE. CONCLUSIONS: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.

Fibrinolytic markers could be useful predictors of severity in patients with pulmonary arterial hypertension: a retrospective study.

BACKGROUND: The severity of pulmonary arterial hypertension (PAH) is classified based on mean pulmonary artery pressure (mPAP) levels. However, other markers have not been elucidated. Fibrinolytic markers, such as total plasminogen activator inhibitor-1 (tPAI-1) and thrombomodulin (TM), are known to reflect arterial endothelial function. However, the relationship between serum tPAI-1, TM and pulmonary circulation has not been completely determined. METHODS: This study included 100 consecutive patients (38 men), with a mean age of 68.9 ± 12.0 years, with cardiac diseases who underwent right heart catheterization. Serum coagulation and fibrinolytic marker levels were measured. RESULTS: The average mPAP value was 25.1 ± 13.1 mmHg for all patients. The mPAP levels revealed a significant positive correlation with serum tPAI-1 (ρ = 0.24, p = 0.042) and uric acid (ρ = 0.29, p = 0.0031) levels. In the group with mPAP levels less than 25 mmHg (n = 58, ave. 17.3 ± 4.3 mmHg), mPAP levels showed a significant positive correlation with serum tPA-1 (ρ = 0.34, p = 0.034) and TM (ρ = 0.34, p = 0.043) values. The mean tPAI-1 (29.8 ± 23.3 ng/ml, p = 0.047) and uric acid (5.7 ± 1.8 mg/dl, p = 0.026) levels were significantly less in those with lower mPAP levels. A multivariate analysis revealed that tPAI-1 alone was a significant independent characteristic marker of PAH (odds ratio 1.02, 95%CI 1.000-1.036, p = 0.034). CONCLUSIONS: These results indicate that serum tPAI-1 and TM may be useful predictors of severity, similar to mPAP in patients with PAH. They could be beneficial in predicting PAH among patients in the early stage of the disease.

Circulating oxidized LDL, increased in patients with acute myocardial infarction, is accompanied by heavily modified HDL.

Oxidized LDL (oxLDL) is a known risk factor for atherogenesis. This study aimed to reveal structural features of oxLDL present in human circulation related to atherosclerosis. When LDL was fractionated on an anion-exchange column, in vivo-oxLDL, detected by the anti-oxidized PC (oxPC) mAb, was recovered in flow-through and electronegative LDL [LDL(-)] fractions. The amount of the electronegative in vivo-oxLDL, namely oxLDL in the LDL(-) fraction, present in patients with acute MI was 3-fold higher than that observed in healthy subjects. Surprisingly, the LDL(-) fraction contained apoA1 in addition to apoB, and HDL-sized particles were observed with transmission electron microscopy. In LDL(-) fractions, acrolein adducts were identified at all lysine residues in apoA1, with only a small number of acrolein-modified residues identified in apoB. The amount of oxPC adducts of apoB was higher in the LDL(-) than in the L1 fraction, as determined using Western blotting. The electronegative in vivo-oxLDL was immunologically purified from the LDL(-) fraction with an anti-oxPC mAb. The majority of PC species were not oxidized, whereas oxPC and lysoPC did not accumulate. Here, we propose that there are two types of in vivo-oxLDL in human circulating plasma and the electronegative in vivo-oxLDL accompanies oxidized HDL.

Dapagliflozin Influences Ventricular Hemodynamics and Exercise-Induced Pulmonary Hypertension in Type 2 Diabetes Patients　- A Randomized Controlled Trial.

BACKGROUND: This prospective randomized multicenter open-label trial evaluated whether sodium-glucose cotransporter-2 inhibitor (SGLT2-i) improves left ventricular (LV) pump function and suppresses elevation of LV filling pressure (LVFP) and right ventricular systolic pressure (RVSP) during exercise in type 2 diabetes mellitus (T2DM) patients.Methods and Results:Based on HbA1c and LV ejection fraction, 78 patients with poorly controlled T2DM were randomly assigned to D-group (dapagliflozin 5 mg/day add-on) or C-group (conventional therapy add-on). Physical examination, home and office blood pressure examination, blood tests, and echocardiography at rest and during ergometer exercise were performed at baseline and at 1.5 and 6 months after treatment. The primary endpoint was defined as the change in RVSP (mmHg) between baseline and 6-month follow up. The secondary endpoints were changes in LVFP (ratio), stroke volume index (SVi; mL/m2), and cardiac index (CI; L/min/m2). Both RVSP and LVFP during exercise significantly decreased from baseline to 6 months after starting treatment in the D-group (P<0.001). No changes to either parameter was observed in the C-group. The SVi and CI did not improve in either group. Both home and office blood pressure significantly decreased in the D-group. Decreases in HbA1c were somewhat greater in the C-group. CONCLUSIONS: Dapagliflozin significantly improved RVSP and LVFP during exercise in patients with T2DM and cardiovascular risk, which may contribute to favorable effects on heart failure.

Target of Triglycerides as Residual Risk for Cardiovascular Events in Patients With Coronary Artery Disease　- Post Hoc Analysis of the FMD-J Study A.

BACKGROUND: Circulating triglyceride (TG) levels are a current focus as a residual risk for cardiovascular (CV) events. We evaluated the relationship between circulating TG levels and future CV events in patients with coronary artery disease (CAD) who were treated with conventional therapy. Methods and Results: We analyzed data for 652 patients who were enrolled in the FMD-J Study A. We investigated the associations between serum TG levels and first major CV events (death from CV cause, nonfatal acute coronary syndrome (ACS), nonfatal stroke, and CAD) for a 3-year follow-up period. Patients were divided into 4 groups based on serum TG level: low-normal (<100 mg/dL), high-normal (100-149 mg/dL), borderline hypertriglyceridemia (150-199 mg/dL), and moderate hypertriglyceridemia (≥200 mg/dL). During a median follow-up period of 46.6 months, 14 patients died (9 from CV causes), 16 had nonfatal ACS, 6 had nonfatal stroke, and 54 had CAD. The Kaplan-Meier curves for first major CV event among the 4 groups were significantly different (P=0.04). After adjustment for various confounders, serum TG level ≥100 mg/dL were significantly associated with an increased risk of first major CV events compared with serum TG level <100 mg/dL. CONCLUSIONS: Serum TG level may be a surrogate marker for predicting CV events in patients with CAD.

Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis.

Tumor necrosis factor-stimulated gene-6 (TSG-6) is a 35-kDa glycoprotein that has been shown to exert anti-inflammatory effects in experimental models of arthritis, acute myocardial infarction, and acute cerebral infarction. Several lines of evidence have shed light on the pathophysiological roles of TSG-6 in atherosclerosis. TSG-6 suppresses inflammatory responses of endothelial cells, neutrophils, and macrophages as well as macrophage foam cell formation and vascular smooth muscle cell (VSMC) migration and proliferation. Exogenous TSG-6 infusion and endogenous TSG-6 attenuation with a neutralizing antibody for four weeks retards and accelerates, respectively, the development of aortic atherosclerotic lesions in ApoE-deficient mice. TSG-6 also decreases the macrophage/VSMC ratio (a marker of plaque instability) and promotes collagen fibers in atheromatous plaques. In patients with coronary artery disease (CAD), plasma TSG-6 levels are increased and TSG-6 is abundantly expressed in the fibrous cap within coronary atheromatous plaques, indicating that TSG-6 increases to counteract the progression of atherosclerosis and stabilize the plaque. These findings indicate that endogenous TSG-6 enhancement and exogenous TSG-6 replacement treatments are expected to emerge as new lines of therapy against atherosclerosis and related CAD. Therefore, this review provides support for the clinical utility of TSG-6 in the diagnosis and treatment of atherosclerotic cardiovascular diseases.

Association Between Waist-to-Height Ratio and Endothelial Dysfunction in Patients With Morbidity　- A Report From the FMD-J Study.

BACKGROUND: Waist circumference (WC), waist-to-height ratio (WHtR) and body mass index (BMI) are known as easy anthropometric markers of abnormal obesity and screening tools for predicting cardiovascular outcomes, but which indices are best is unclear. We therefore investigated the superiority and association between each index and low flow-mediated dilatation (FMD) as a surrogate marker for cardiovascular outcomes in patients with morbidity in a large Japanese prospective cohort.Methods and Results:A total of 1,645 Japanese patients who had coronary artery disease and hypertension or diabetes mellitus were enrolled, and 1,087 of them were analyzed. The high-WHtR group (≥0.5) showed greater morbidity and increased inflammation in association with atherosclerosis compared with the low-WHtR group. High WHtR and advanced age were identified as predictors of low FMD (odds ratio (OR) 1.39, 95% confidence interval (CI) 1.02-1.88, P=0.037 and OR 1.55, 95% CI 1.19-2.01, P=0.001, respectively). However, WC was not associated with that risk in either sex (male: OR 1.37, 95% CI 0.97-1.93, P=0.076; female: OR 1.08, 95% CI 0.68-1.73, P=0.74), and no association was evident between high BMI and low FMD (OR 0.92, 95% CI 0.71-1.19, P=0.54). CONCLUSIONS: WHtR offers a superior predictor of decreased FMD than other anthropometric indices, and progression of arteriosclerosis might be detected more sensitively. Further study is needed to investigate the relationship between cardiovascular mortality and WHtR.

Does Treatment of Impaired Glucose Tolerance Improve Cardiovascular Outcomes in Patients with Previous Myocardial Infarction?

PURPOSE: We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT). METHODS: This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure. RESULTS: The age, ratio of males, and HbA1C were 65 vs. 65 years, 86 vs. 87%, and 5.6 vs. 5.5% in the groups with and without voglibose, respectively. Voglibose improved IGT; however, Kaplan-Meier analysis showed no significant between-group difference with respect to cardiovascular events [12.5% with voglibose vs. 10.1% without voglibose for the primary endpoint (95% confidence interval, 0.82-1.86)]; there were no significant differences in secondary endpoints. CONCLUSION: Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT00212017.

Method for estimating high sdLDL-C by measuring triglyceride and apolipoprotein B levels.

BACKGROUND: We previously developed an assay to directly measure small dense (sd) low-density lipoprotein cholesterol (LDL-C) levels, which is not widely used in general clinical practice. Therefore, we propose a simpler method, "LDL window," that uses conventional methods for estimating high sdLDL-C levels. METHODS: We analyzed our previous studies (2006-2008) on healthy subjects and patients with type 2 diabetes and coronary artery disease (CAD). The sdLDL-C level was measured using the precipitation method, and LDL size was determined using gradient gel electrophoresis. The "LDL window" comprises the estimation of LDL particle number and size. We adopted apolipoprotein B (apoB) for the estimation of the LDL particle number and used 110 mg/dL as the cutoff value for hyper-apoB. Triglycerides (TGs) are a powerful inverse determinant of LDL particle size. Therefore, we adopted TG for the estimation of the LDL particle size and used 150 mg/dL as the cutoff value for hyper-TG. Subjects were stratified into the following four subgroups: normal, hyper-TG, hyper-apoB, and hyper-TG/-apoB. Non-high-density lipoprotein cholesterol (non-HDL-C) is a surrogate marker for apoB; therefore, the "alternative LDL window" comprised non-HDL-C (cutoff, 170 mg/dL) and TG. RESULTS: The top quartile (Q4) of sdLDL-C (>31 mg/dL) doubled in patients with diabetes and CAD. The hyper-TG/-apoB group in the "LDL window" represented >90% Q4 and <4% Q1 and Q2, irrespective of the subjects. The sdLDL-C levels in the hyper-TG/-apoB group were 50% higher in patients with diabetes and CAD than those in controls. Similar results were obtained using the "alternative LDL window." CONCLUSIONS: Our proposed "LDL window" may help identify patients at high risk of CAD independent of LDL-C.

Effects of Phase II Comprehensive Cardiac Rehabilitation on Coronary Plaque Volume After Acute Coronary Syndrome.

The present study aimed to determine the effects of phase II (PII) comprehensive cardiac rehabilitation (CR) on coronary plaque volume in patients after acute coronary syndrome (ACS).We assigned 46 patients with ACS who had undergone standard phase I CR into groups who proceeded with PII-CR (PII-CR; n = 21) and those who did not (non-PII-CR; n = 25). We then measured anthropometric parameters and daily physical activity using a pedometer for up to 60 days. The isokinetic strength of the knee extensor and flexor muscles and exercise tolerance were tested and non-culprit lesions were analyzed using volumetric intravascular ultrasound at baseline and 6 months later.Baseline characteristics did not significantly differ between the two groups and exercise tolerance was significantly improved in both. Waist size and fat weight were significantly decreased, and muscle strength was significantly increased in the PII-CR group but not in the non-PII-CR group. The percent change in plaque volume (primary endpoint) did not differ significantly between the two groups. The percent change in plaque volume was significantly and negatively correlated with daily physical activity.Although risk factors, muscle strength, and exercise tolerance were improved by PII-CR, plaque regression did not differ significantly between the two study groups. A significant correlation between percent change in coronary plaque volume and physical activity was observed. A comprehensive phase II-CR, including frequent supervised exercise sessions and a program encouraging an increase in daily physical activity, may reduce plaque volume in patients after ACS (UMIN000006038).

Higher Cholesterol Absorption Marker at Baseline Predicts Fewer Cardiovascular Events in Elderly Patients Receiving Hypercholesterolemia Treatment: The KEEP Study.

BACKGROUND: Higher cholesterol absorption has been reported to be related to a higher incidence of cardiovascular events (CVEs). The KEEP (Kyushu Elderly Ezetimibe Phytosterol) study, a substudy of the EWTOPIA 75 (Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older) study, investigated the relationships of cholesterol absorption and synthesis markers with CVEs in older old individuals with hypercholesterolemia, particularly in relation to ezetimibe treatment. METHODS AND RESULTS: Eligible patients were those aged ≥75 years who had low-density lipoprotein cholesterol ≥140 mg/dL, no history of coronary artery disease, and no recent use of lipid-lowering drugs. Participants were randomly assigned into a diet-only or diet-plus-ezetimibe group. Baseline and 24-week follow-up blood samples were analyzed for cholesterol absorption (eg, campesterol) and synthesis markers (eg, lathosterol). Of 1287 patients, 1061 patients with baseline measurement were analyzed. Over a median follow-up of 4.0 years, 64 CVEs occurred. Higher campesterol levels at baseline were significantly associated with a lower risk of CVEs. After adjustment for sex, age, and treatment, the hazard ratios for the lowest to highest quartile categories of baseline campesterol were 1.00 (reference), 0.59 (95% CI, 0.30-1.17), 0.44 (95% CI, 0.21-0.94), and 0.44 (95% CI, 0.21-0.93), respectively (trend P=0.01). This association persisted after further adjustment for hypertension, diabetes, and other cardiovascular risk factors. Neither interactions with ezetimibe treatment nor mediating effects of the changes in cholesterol absorption markers were observed. CONCLUSIONS: The KEEP study indicated that higher campesterol levels without lipid-lowering drugs were associated with a lower incidence of CVEs in older old individuals with hypercholesterolemia who were subsequently treated with diet or ezetimibe. REGISTRATION: URL: https://www.umin.ac.jp; unique identifier: UMIN000017769.

Role of Small Dense Low-density Lipoprotein Cholesterol in Cardiovascular Events in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Receiving Statin Treatment.

AIM: There is little information on the relationships of serum small dense low-density lipoprotein cholesterol (sdLDL-C) levels and serum triglyceride (TG) levels with cardiovascular events in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (DM) who are receiving statins. The aim of this study was to evaluate the relationships of serum TG levels and sdLDL-C levels as residual risks for cardiovascular events in patients with CAD and type 2 DM who were being treated with statins. METHODS: The subjects were divided into four groups based on TG levels and sdLDL-C levels: sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL, sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, and sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL. During a median follow-up period of 1419 days, cardiovascular events occurred in 34 patients. RESULTS: The incidences of cardiovascular events were significantly higher in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ＜150 mg/dL and in patients with sdLDL-C of ≥ 40.0 mg/dL and TG of ≥ 150 mg/dL, but not in patients with sdLDL-C of ＜40.0 mg/dL and TG of ≥ 150 mg/dL, than in patients with sdLDL-C of ＜40.0 mg/dL and TG of ＜150 mg/dL. CONCLUSIONS: Under the condition of treatment with statins, patients with CAD and type 2 DM who had sdLDL-C levels of ≥ 40.0 mg/dL had a high risk for cardiovascular events even though serum TG levels were controlled at ＜150 mg/dL.

[Statin therapy for atherogenic hypertriglyceridemia].

LDL-cholesterol lowering by statins substantially reduces morbidity and mortality of coronary heart disease (CHD) and ischemic stroke. Statins are the most potent agents for lowering circulating LDL particles. Accumulation of triglyceride-rich remnant lipoproteins in both fasting and postprandial state is strongly associated with the formation of highly atherogenic small dense LDL. Although dose-dependent reductions in levels of atherogenic lipids are observed with all statin, strong statins such as rosuvastatin, atorvastatin, and pitavastatin, can reduce the triglyceride and small dense LDL greater than other statins. Statin is one of the first-line drugs for management of hypertriglyceridemia with elevated LDL-cholesterol and/or non HDL-cholesterol. Aggressive LDL-cholesterol lowering may be required for the management of high-risk CHD patients with both high LDL-cholesterol and triglyceride.

Reduced reactive hyperemia of the brachial artery in diabetic patients assessed by repeated measurements: The FMD-J B study.

Type 2 diabetes mellitus (T2DM) is a major cause of microvascular dysfunction. However, its effect on blood flow patterns during ischemic demand has not been adequately elucidated. In this study, we investigated the hypothesis that microvascular dysfunction in patients with T2DM manifests as brachial reactive hyperemia (BRH), defined as the ratio of peak blood flow velocities in a brachial artery before and after forearm cuff occlusion. The study enrolled 943 subjects (men, n = 152 [T2DM] and n = 371 [non-T2DM]; women, n = 107 [T2DM] and n = 313 [non-T2DM], respectively) with no history of cardiovascular disease. Semiautomatic measurements were obtained three times at 1.5-year intervals to confirm the reproducibility of factors involved in BRH for each sex. An age-adjusted mixed model demonstrated attenuated BRH in the presence of T2DM in both men (p = 0.022) and women (p = 0.031) throughout the study period. Post hoc analysis showed that the estimated BRH was significantly attenuated in patients with T2DM regardless of sex, except at baseline in women. In multivariate regression analysis, T2DM was a negative predictor of BRH at every measurement in men. For women, BRH was more strongly associated with alcohol consumption. Repeated measurements analysis revealed that T2DM was associated with attenuated postocclusion reactive hyperemia.

Evaluation of the efficacy and safety of an integrated telerehabilitation platform for home-based cardiac REHABilitation in patients with heart failure (E-REHAB): protocol for a randomised controlled trial.

INTRODUCTION: Cardiac rehabilitation (CR) is strongly recommended as a medical treatment to improve the prognosis and quality of life of patients with heart failure (HF); however, participation rates in CR are low compared with other evidence-based treatments. One reason for this is the geographical distance between patients' homes and hospitals. To address this issue, we developed an integrated telerehabilitation platform, RH-01, for home-based CR. We hypothesised that using the RH-01 platform for home-based CR would demonstrate non-inferiority compared with traditional centre-based CR. METHODS AND ANALYSIS: The E-REHAB trial aims to evaluate the efficacy and safety of RH-01 for home-based CR compared with traditional centre-based CR for patients with HF. This clinical trial will be conducted under a prospective, randomised, controlled and non-inferiority design with a primary focus on HF patients. Further, to assess the generalisability of the results in HF to other cardiovascular disease (CVD), the study will also include patients with other CVDs. The trial will enrol 108 patients with HF and 20 patients with other CVD. Eligible HF patients will be randomly assigned to either traditional centre-based CR or home-based CR in a 1:1 fashion. Patients with other CVDs will not be randomised, as safety assessment will be the primary focus. The intervention group will receive a 12-week programme conducted two or three times per week consisting of a remotely supervised home-based CR programme using RH-01, while the control group will receive a traditional centre-based CR programme. The primary endpoint of this trial is change in 6 min walk distance. ETHICS AND DISSEMINATION: The conduct of the study has been approved by an institutional review board at each participating site, and all patients will provide written informed consent before entry. The report of the study will be disseminated via scientific fora, including peer-reviewed publications and presentations at conferences. TRIAL REGISTRATION NUMBER: jRCT:2052200064.

Assessment of Residual Vasospasm in Patients with Plaque Rupture or Plaque Erosion using Optical Coherence Tomography.

AIMS: Coronary vasospasm is associated with acute coronary syndrome (ACS) and may persist during primary percutaneous coronary intervention (PCI). We aimed to elucidate the incidence, morphological characteristics, and prognostic impact of residual vasospasm in plaque rupture (PR) and plaque erosion (PE) lesions using optical coherence tomography (OCT). METHODS: We enrolled 142 patients with ACS who underwent OCT-guided primary PCI. All patients received intracoronary vasodilators before OCT examination. Residual vasospasm was identified as intimal gathering and categorised as polygonal- or wavy- patterned depending on the luminal shape. A wavy pattern was defined as a curved intimal surface line. A polygonal pattern was defined as a lumen with multiple angles. The incidence of major cardiovascular events, defined as death, non-fatal myocardial infarction, stroke, and any revascularization, within 1-year of PCI was identified. RESULTS: The prevalence of residual vasospasm in PR and PE was 15.1% (13 of 86) and 21.4% (12 of 56), respectively. Wavy pattern was the major shape of the residual vasospasm. Polygonal-patterned lumen was more frequently observed in PR than in PE (38.5 vs. 8.3 %). The polygonal-patterned lumens had significantly larger lipid arcs (257.9 vs. 78.0 °; P＜0.01), and significantly smaller areas (1.27 vs. 1.88 mm2; P=0.05) than wavy patterned lumens. Residual vasospasm had a prognostic impact on PR but not PE at 1-year of successful primary PCI. CONCLUSION: Considerable proportion of ACS including both PR and PE had residual vasospasm with variable morphological feature and different prognostic impact.