Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Background: and Purpose In young patients (aged 18–60 years) with patent foramen ovale (PFO)- associated stroke, percutaneous closure has been found to be useful for preventing recurrent ischemic stroke or transient ischemic attack (TIA). However, it remains unknown whether PFO closure is also beneficial in older patients. Methods: Patients aged ≥60 years who had a cryptogenic stroke and PFO from ten hospitals in South Korea were included. The effect of PFO closure plus medical therapy over medical therapy alone was assessed by a propensity-score matching method in the overall cohort and in those with a high-risk PFO, characterized by the presence of an atrial septal aneurysm or a large shunt. Results: Out of the 437 patients (mean age, 68.1), 303 (69%) had a high-risk PFO and 161 (37%) patients underwent PFO closure. Over a median follow-up of 3.9 years, recurrent ischemic stroke or TIA developed in 64 (14.6%) patients. In the propensity score-matched cohort of the overall patients (130 pairs), PFO closure was associated with a significantly lower risk of a composite of ischemic stroke or TIA (hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.24–0.84; P=0.012), but not for ischemic stroke. In a subgroup analysis of confined to the high-risk PFO patients (116 pairs), PFO closure was associated with significantly lower risks of both the composite of ischemic stroke or TIA (HR: 0.40; 95% CI: 0.21–0.77; P=0.006) and ischemic stroke (HR: 0.47; 95% CI: 0.23–0.95; P=0.035). Conclusion Elderly patients with cryptogenic stroke and PFO have a high recurrence rate of ischemic stroke or TIA, which may be significantly reduced by device closure.

Background and Objectives: Concerns remain that early aspirin cessation may be associated with potential harm in subsets at high risk of ischemic events. This study aimed to assess the effects of P2Y12 inhibitor monotherapy after 3-month dual antiplatelet therapy (DAPT) vs.prolonged DAPT (12-month or longer) based on the ischemic risk stratification, the CHADSP2A2RC, after percutaneous coronary intervention (PCI). Methods: This was a sub-study of the SMART-CHOICE trial. The effect of the randomized antiplatelet strategies was assessed across 3 CHADS-P2A2RC risk score categories. The primary outcome was a major adverse cardiac and cerebral event (MACCE), a composite of all-cause death, myocardial infarction, or stroke. Results: Up to 3 years, the high CHADS-P2A2RC risk score group had the highest incidence of MACCE (105 [12.1%], adjusted hazard ratio [HR], 2.927; 95% confidence interval [CI], 1.358–6.309; p=0.006) followed by moderate-risk (40 [1.4%], adjusted HR, 1.786; 95% CI, 0.868–3.674; p=0.115) and low-risk (9 [0.5%], reference). In secondary analyses, P2Y12 inhibitor monotherapy reduced the Bleeding Academic Research Consortium (BARC) types 2, 3, or 5 bleeding without increasing the risk of MACCE as compared with prolonged DAPT across the 3 CHADS-P2A2RC risk strata without significant interaction term (interaction p for MACCE=0.705 and interaction p for BARC types 2, 3, or 5 bleeding=0.055). Conclusions The CHADS-P2A2RC risk score is valuable in discriminating high-ischemicrisk patients. Even in such patients with a high risk of ischemic events, P2Y12 inhibitor monotherapy was associated with a lower incidence of bleeding without increased risk of ischemic events compared with prolonged DAPT.

Background and Objectives: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in realworld practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors. Methods: From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention). Results: Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471;p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3–4 years. Conclusions In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes.

Background and Objectives: Limited data are available regarding long-term clinical outcomes of iliac artery endovascular therapy (EVT) in real-world practice. This study investigated long-term outcomes according to Trans-Atlantic Inter-Society Consensus (TASC) classifications. Methods: We analyzed data from 1,705 limbs of 1,364 patients from the retrospective cohort of the multicenter Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry. The primary endpoint was target lesion revascularization (TLR)-free survival. Results: TASC A, B, C, and D lesions were present in 19.4%, 26.2%, 28.7%, and 25.7% of the treated limbs, respectively. The technical success rate was 96.2% and did not differ between TASC lesion types. Complications occurred in 6.8% of cases and more occurred in TASC D (11.8%). Iliac artery EVT showed a 5-year TLR-free survival of 89.2%. The TASC D group had the lowest TLR-free rate of 79.3%. TASC D (hazard ratio [HR], 1.75; 95% confidence interval [CI], 1.12–2.73; p=0.014), plain old balloon angioplasty (HR, 4.25; 95% CI, 2.03–8.88; p<0.001), current smoker (HR, 1.89; 95% CI, 1.26–2.83; p=0.002), previous bypass surgery (HR, 3.04;95% CI, 1.28–7.19; p=0.011), combined femoropopliteal treatment (HR, 4.89; 95% CI, 3.19–7.50; p<0.001), combined below the knee treatment (HR, 2.20; 95% CI, 1.25–3.89; p=0.007), and complications (HR, 1.86; 95% CI, 1.07–3.24; p=0.028) were predictors for TLR. Conclusions Iliac artery EVT achieved excellent technical success and 5-year TLR-free survival. TASC D showed a favorable but lower 5-year TLR-free survival rate and higher complication rate compared with other TASC groups.

Background and Objectives: Studies evaluating the nature of ischemic burden of chronic total occlusion (CTO) vessels are still lacking. Methods: A total of 165 patients with single vessel CTO >2.5 mm in an epicardial coronary artery who underwent single photon emission computed tomography (SPECT) were enrolled in the study. Ischemic burden was calculated with the use of semi-quantitative SPECT analysis, and was defined as the summed difference score (SDS) divided by the maximal limit of the score (=SDS/68). Results: The mean age of the participants was 59.5 years and the CTO of the left anterior descending coronary artery (LAD), left circumplex coronary artery (LCX), and right coronary artery (RCA) accounted for 93 (56.4%), 18 (10.9%), and 54 (32.7%) patients, respectively. The median ischemic burden of the total population was 8.8%, and it was highest in the LAD CTO (10.3%) compared with the LCX (5.9%) and RCA CTO (5.9%, p<0.001). High-ischemic burden (ischemic burden >10%) was observed in 66 patients (40.0%), and in 47 patients (50.5%) of the LAD CTO. Ischemic burden was different according to the CTO location only in LAD CTO. The statistically significant predictors for high-ischemic burden were hypertension, baseline ejection fraction >45%, LAD CTO, proximal CTO location, and de novo CTO. Japanese-CTO score and Rentrop scale collateral grade were not associated with high-ischemic burden. Conclusions Only 40% of patients with single vessel CTO had ischemic burden >10%. For CTO vessels, measurement of ischemic burden using SPECT prior to revascularization may be helpful in identifying beneficial subjects.

Background: Outcomes of traditional treatment for osteonecrosis of the femoral head (ONFH) are not always satisfactory. Hence, cell-supplementation therapy has been attempted to facilitate necrotic-tissue regeneration. Adipose-derived mesenchymal stem cell (ADMSC) transplantation is potentially advantageous over bone marrow-derived MSC implantation, but its outcomes for ONFH remain unclear. The aim of this study was to determine 2-year radiological and clinical outcomes of culture-expanded autologous ADMSC implantation for ONFH. Methods: Eighteen hips with necrotic lesions involving ≥ 30% of the femoral head were included. ADMSCs were harvested by liposuction and culture expanded for 3 passages over 3 weeks. With a 6-mm single drilling, ADMSCs were implanted into the necrotic zone. All patients underwent magnetic resonance imaging (MRI), single-photon emission computed tomography/computed tomography (SPECT/CT) at screening and 6 months, 12 months, and 24 months postoperatively. The primary outcome was the change in the size of necrotic area on MRI. Secondary outcomes were changes in clinical scores and radioisotope uptake on SPECT/CT. Conversion total hip arthroplasty (THA) was defined as the endpoint. Results: Preoperatively, the necrotic lesion extent was 63.0% (38.4%–96.7%) of the femoral head. The mean Harris hip score was 89.2, the University of California at Los Angeles (UCLA) score was 5.6, and Western Ontario and McMaster Universities Arthritis index (WOMAC) was 79.4. Three patients underwent THA and 1 patient died in an accident. Finally, 11 patients (14 hips) were available for ≥ 2-year follow-up. At the last follow-up, no surgery-related complications occurred, and 14 of 17 hips (82%) were able to perform daily activities without THA requirement. There was no significant decrease in lesion size between any 2 intervals on MRI.However, widening of high signal intensity bands on T2-weighted images inside the necrotic lesion was observed in 9 of 14 hips (64%); 11 of 14 hips (79%) showed increased vascularity on SPECT/CT at 2 years postoperatively. No significant differences were observed between preoperative and 24-month mean Harris hip score (89.2 vs. 88.6), WOMAC (79.4 vs. 75.7), and UCLA score (5.6 vs. 6.2). Conclusions Our outcomes suggest that culture-expanded ADMSC implantation is a viable option for ONFH treatment without adverse events.