Drug-coated balloon versus drug-eluting stent for femoropopliteal total occlusions: intraluminal versus subintimal approaches.

Because there is a lack of comparative studies assessing drug-coated balloon (DCB) and drug-eluting stent (DES) outcomes with respect to intraluminal (IL) and subintimal (SI) approaches in femoropopliteal (FP) total occlusive lesions, we compared the outcomes between DCB (including bailout stenting) and DES treatments for this lesion. A total of 487 limbs (434 patients) were divided into the IL (n = 344, DCB: n = 268, DES: n = 76) and SI (n = 143, DCB: n = 83, DES: n = 60) approach groups. The primary outcome was a major adverse limb event (MALE), defined as above-ankle amputation or repeat revascularization of the index limb. Secondary outcomes included clinically driven target lesion revascularization (TLR), loss of clinical patency, and all-cause death. After adjustment, in each IL and SI approach, the 2-year rates of MALE (p = 0.180 and p = 0.236, respectively), TLR, loss of clinical patency, and all-cause death were similar between the DCB and DES groups. In the DCB and DES groups, both primary and secondary outcomes were similar between the IL and SI approaches. DCB and DES strategies for patients presenting with FP total occlusive lesions demonstrated similar outcomes regardless of the IL or SI approach.Clinical Trial Registration: NCT02748226.

Treatment extent of femoropopliteal disease and clinical outcomes following endovascular therapy.

BACKGROUND: Endovascular therapy (EVT) has become the preferred treatment modality for femoropopliteal disease. However, there is limited evidence regarding its procedural and clinical outcomes according to the affected area. AIMS: The aim of this study is to investigate clinical outcomes and device effectiveness according to treatment extent in the superficial femoral artery (SFA), popliteal artery (PA), or both. METHODS: In this study, we analysed EVT for SFA (2,404 limbs), PA (155 limbs), SFA/PA (383 limbs) using the population in the K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) registry. The primary endpoint was target lesion revascularisation (TLR) at 2 years. RESULTS: The SFA/PA group exhibited a higher prevalence of anatomical complexity, characterised by long lesions, moderate to severe calcification, and total occlusion. The procedures were successful in 97.2% of SFA, 92.9% of PA, and 95.6% of SFA/PA EVTs. The 2-year TLR rates were 21.1%, 18.6%, and 32.7% in the SFA, PA, and SFA/PA groups, respectively. SFA/PA EVT was associated with a significantly increased risk for TLR compared to the SFA group (adjusted hazard ratio [HR] 1.48 [1.09-2.00]; p=0.008) and a trend towards an increased risk compared to the PA group (adjusted HR 1.80 [1.00-3.27]; p=0.052). After overlap weighting, the use of a drug-coated balloon (DCB) was shown to be beneficial, with the lowest TLR rate after SFA and SFA/PA EVT. CONCLUSIONS: In this large real-world registry, SFA/PA EVT was associated with an increased risk for TLR at 2 years compared to the SFA or PA EVT groups, with favourable outcomes when using a DCB or drug-eluting stent in the SFA/PA EVT group.

Korean Multicenter Registry of ELUVIA Stent for Femoropopliteal Artery Disease: K-ELUVIA Registry.

BACKGROUND AND OBJECTIVES: The K-ELUVIA study aimed to investigate the clinical effectiveness and safety of Eluvia™, a polymer-coated, paclitaxel-eluting stent, for femoropopliteal artery disease using data from a prospective Korean multicenter registry. METHODS: A total of 105 patients with femoropopliteal artery disease who received endovascular treatment (EVT) with Eluvia™ stents at 7 Korean sites were enrolled in a prospective cohort and followed for 2 years. The primary endpoint was the 2-year clinical patency. The secondary endpoint was 2-year freedom from clinically driven target lesion revascularization (TLR). RESULTS: Mean patient age was 68.2±10.4 years, and most patients (82.7%) were male. Mean lesion length was 168.3±117.6 mm. Chronic total occlusion was found in 57.7% of patients. Trans-Atlantic Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) type C or D lesions were present in 46.1% of patients. Procedural success was achieved in 99.0% of patients. The clinical patency rate was 84.4% at 1 year after EVT and 76.3% at 2 years post-EVT. The freedom from TLR rate was 89.1% at 1 year after EVT and 79.1% at 2 years post-EVT. Chronic total occlusion (hazard ratio [HR], 3.53; 95% confidence interval [CI], 1.08-11.67; p=0.039) and smaller mean stent diameter (HR, 0.40; 95% CI, 0.16-0.98; p=0.044) were identified as independent predictors of loss of clinical patency at 2 years. CONCLUSIONS: The K-ELUVIA study demonstrated favorable 2-year clinical effectiveness and safety outcomes of Eluvia stent for femoropopliteal artery lesions in real-world practice.

Determinants and effects of microvascular obstruction on serial change in left ventricular diastolic function after reperfused acute myocardial infarction.

Background: Although left ventricular (LV) diastolic dysfunction is more related to functional capacity after acute myocardial infarction (AMI), the determinants of LV diastolic functional change after reperfused AMI remain unknown. This study aimed to investigate the effects of microvascular obstruction (MVO) on mid-term changes in LV diastolic function after reperfused AMI. Methods: In a cohort of 72 AMI patients who underwent successful revascularization, echocardiography and cardiovascular magnetic resonance imaging were repeated at 9-month intervals. The late gadolinium enhancement (LGE) amount, segmental extracellular volume fraction, global LV, and left atrial (LA) phasic functions, along with mitral inflow and tissue Doppler measurements, were repeated. Results: Among the included patients, 31 (43%) patients had MVO. During the 9-month interval, LV ejection fraction (EF) and LV global longitudinal strain (GLS) were significantly improved in accordance with a decrease in LGE amount (from 18.2 to 10.3 g, p < 0.001) and LV mass. The deceleration time (DT) of early mitral inflow (188.6 ms-226.3 ms, p < 0.001) and LV elastance index (Ed; 0.133 1/ml-0.127 1/ml, p = 0.049) were significantly improved, but not in conventional diastolic functional indexes. Their improvements occurred in both groups; however, the degree was less prominent in patients with MVO. The degree of decrease in LGE amount and increase in LVEF was significantly correlated with improvement in LV-Ed or LA phasic function, but not with conventional diastolic functional indexes. Conclusions: In patients with reperfused AMI, DT of early mitral inflow, phasic LA function, and LV-Ed were more sensitive diastolic functional indexes. The degree of their improvement was less prominent in patients with MVO.

P2Y12 Inhibitor Monotherapy vs Dual Antiplatelet Therapy After Deployment of a Drug-Eluting Stent: The SHARE Randomized Clinical Trial.

Importance: P2Y12 inhibitor monotherapy after dual antiplatelet therapy (DAPT; a P2Y12 inhibitor plus aspirin) for a brief duration has recently emerged as an attractive alternative for patients undergoing percutaneous coronary intervention (PCI) with a drug-eluting stent. Objective: To investigate whether P2Y12 inhibitor monotherapy after 3 months of DAPT was noninferior to 12 months of DAPT following PCI with a drug-eluting stent. Design, Setting, and Participants: The Short-Term Dual Antiplatelet Therapy After Deployment of Bioabsorbable Polymer Everolimus-Eluting Stent (SHARE) open-label, noninferiority randomized clinical trial was conducted from December 15, 2017, through December 14, 2020. Final 1-year clinical follow-up was completed in January 2022. This study was a multicenter trial that was conducted at 20 hospitals in South Korea. Patients who underwent successful PCI with bioabsorbable polymer everolimus-eluting stents were enrolled. Interventions: Patients were randomly assigned to receive P2Y12 inhibitor monotherapy after 3 months of DAPT (n = 694) or 12 months of DAPT (n = 693). Main Outcomes and Measures: The primary outcome was a net adverse clinical event, a composite of major bleeding (based on Bleeding Academic Research Consortium type 3 or type 5 bleeding) and major adverse cardiac and cerebrovascular events (cardiac death, myocardial infarction, stent thrombosis, stroke, or ischemia-driven target lesion revascularization) between 3 and 12 months after the index PCI. The major secondary outcomes were major adverse cardiac and cerebrovascular events and major bleeding. The noninferiority margin was 3.0%. Results: Of the total 1452 eligible patients, 65 patients were excluded before the 3-month follow-up, and 1387 patients (mean [SD] age, 63.0 [10.7] years; 1055 men [76.1%]) were assigned to P2Y12 inhibitor monotherapy (n = 694) or DAPT (n = 693). Between 3 and 12 months of follow-up, the primary outcome (using Kaplan-Meier estimates) occurred in 9 patients (1.7%) in the P2Y12 inhibitor monotherapy group and in 16 patients (2.6%) in the DAPT group (absolute difference, -0.93 [1-sided 95% CI, -2.64 to 0.77] percentage points; P < .001 for noninferiority). For the major secondary outcomes (using Kaplan-Meier estimates), major adverse cardiac and cerebrovascular events occurred in 8 patients (1.5%) in the P2Y12 inhibitor monotherapy group and in 12 patients (2.0%) in the DAPT group (absolute difference, -0.49 [95% CI, -2.07 to 1.09] percentage points; P = .54). Major bleeding occurred in 1 patient (0.2%) in the P2Y12 inhibitor monotherapy group and in 5 patients (0.8%) in the DAPT group (absolute difference, -0.60 [95% CI, -1.33 to 0.12] percentage points; P = .10). Conclusions and Relevance: In patients with coronary artery disease undergoing PCI with the latest generation of drug-eluting stents, P2Y12 inhibitor monotherapy after 3-month DAPT was not inferior to 12-month DAPT for net adverse clinical events. Considering the study population and lower-than-expected event rates, further research is required in other populations. Trial Registration: ClinicalTrials.gov Identifier: NCT03447379.

Device Effectiveness for Femoropopliteal Artery Disease Treatment: An Analysis of K-VIS ELLA Registry.

BACKGROUND: Although drug-coated balloons (DCBs) and drug-eluting stents (DES) are frequently used for the treatment of femoropopliteal artery (FPA) disease, their mid- or long-term clinical efficacy in real-world practice is still limited. OBJECTIVES: From the K-VIS ELLA (Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases) multicenter registry cohort, clinical outcomes of drug-eluting devices for FPA lesions in comparison with bare-metal stents (BMS) were evaluated. METHODS: Limbs that underwent percutaneous transluminal angioplasty for FPA lesions with plain old balloon angioplasty (POBA, n = 826), BMS (n = 943), DCBs (n = 778), or DES (n = 227) between 2012 and 2020 were included. The primary outcome was target lesion revascularization (TLR) at 2 years. Inverse probability of treatment weighting was used to account for confounding. RESULTS: After inverse probability of treatment weighting, baseline characteristics were well-balanced among groups. Compared with the 2-year cumulative incidence of TLR with BMS (26.5%), the incidence of TLR was significantly lower in limbs treated with DCBs (15.9%; HR: 0.44; 95% CI: 0.30-0.64; P < 0.001) or DES (15.9%; HR: 0.51; 95% CI: 0.29-0.87; P = 0.014). No significant differences were observed in the risk of TLR between DCBs vs DES (HR: 0.87; 95% CI: 0.51-1.49; P = 0.613) and POBA vs BMS (HR: 0.94; 95% CI: 0.73-1.21; P = 0.626). All-cause mortality was comparable in the 4 groups. Treatment with DCBs showed a more pronounced favorable outcome in limbs with Trans-Atlantic Inter-Society Consensus II type C/D lesions or long lesions (≥150 mm) compared with POBA, BMS, or DES (Pinteraction< 0.05). CONCLUSIONS: In real-world practice, DCBs and DES demonstrated comparably superior midterm outcomes over POBA or BMS in the treatment of FPA lesions.

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.

Arterial Stiffness is Associated with False-Positive ST-Segment Depression in Supine Bicycle Exercise Stress Echocardiography.

Background: Although exercise stress electrocardiography (ECG) is a popular tool for detecting coronary artery disease (CAD), the induced ST-depression without coronary artery stenosis (FST) remains a challenge for accurate diagnosis. Exercise-induced ST depression is related to poor prognosis even in non-obstructive disease; however, its determinants have not been fully defined. We sought to investigate whether ventriculo-vascular interactional indexes such as arterial stiffness index, exercise hemodynamic parameters and echocardiographic left ventricular (LV) functional parameters were related to FST. Methods: In the current study, 609 participants who underwent both supine bicycle exercise echocardiography and brachial-ankle pulse wave velocity (baPWV) measurement without exercise-induced regional wall motion abnormalities (RWMA) were analyzed. Referral reasons for stress test were CAD detection or evaluation of patency of previous revascularization. Stepwise graded supine bicycle exercise was performed with simultaneous ECG recording and echocardiography after full conventional resting echocardiography. The FST was defined as newly developed > 1 mm ST depression without RWMA during exercise. Results: The median age of the study participants was 65 (59.0-70.5) years, and 222 (37%) patients were women. Among them, 103 (17%) patients showed FST during the exercise or recovery phase. The prevalence of FST did not differ between sexes. Older age, higher pulmonary arterial systolic pressure (PASP), left atrial volume index, baPWV and ankle brachial index at rest and hypertensive response, higher heart rate and rate-pressure product at peak exercise were significantly associated with FST. In multivariate analysis, higher peak heart rate, PASP, and baPWV were independently related to FST. Conclusions: Stress-induced RWMA in addition to ECG should be evaluated to detect CAD in patients with higher baPWV and PASP. FST might be linked to subclinical myocardial ischemia through arterial stiffness and diastolic dysfunction.

Long coverage with drug-eluting stents is superior to spot coverage for long femoropopliteal artery disease: PARADE II study.

Background: The efficacy of spot stenting using drug-eluting stents (DES) for the treatment of long femoropopliteal (FP) lesion is unknown. This study aimed to compare clinical outcomes of long full coverage vs. spot coverage with DES for long FP artery disease. Methods: This multicenter randomized trial compared long DES vs. spot DES for FP lesions longer than 150 mm. All lesions were treated with paclitaxel-eluting stents (Zilver PTX). The primary endpoint was primary patency at 12 months. Results: The study was terminated early after an interim analysis. A total of 103 patients (55 in the long DES group; 48 in the spot DES group) were eligible for analysis. There were no significant differences in baseline and lesion characteristics between groups. Total stent length was longer in the long DES group than in the spot DES group (225.6 ± 67.2 vs. 131.3 ± 48.7 mm, p < 0.001). Technical success was achieved in all patients. There was a trend toward a higher primary patency rate at 12 months in the long DES group than in the spot DES group (87.5% vs. 67.5%, p = 0.120). The rate of survival free from target lesion revascularization was significantly higher in the long DES group than in the spot DES group (91.7% vs. 72.0%, p = 0.044). In multivariate Cox regression analysis, spot DES [hazard ratio (HR) 2.42, 95% confidence interval (CI) 1.14-5.12, p = 0.021] and postdilation (HR 0.27, 95% CI 0.09-0.79, p = 0.018) were identified as independent predictors for loss of patency at 12 months post-procedure. Conclusions: Long DES were more effective than spot DES for treating long FP lesions. Clinical trial registration: Clinicaltrials.gov, identifier: NCT02701881.

The association between cardiac involvement and long-term clinical outcomes in patients with Duchenne muscular dystrophy.

AIMS: Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long-term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long-term clinical outcomes and their associated factors in patients with late-stage DMD. METHODS AND RESULTS: A total of 116 patients with late-stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all-cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow-up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log-rank P = 0.005). In the multivariable Cox regression analysis, brain-natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019-1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651-52.148, P = 0.011) were significant predictors of all-cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log-rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005-1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704-10.296, P = 0.002) were significant predictors of the composite event in patients with DMD. CONCLUSIONS: Patients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late-stage DMD, irrespective of LVEF.

Long-Term Clinical Outcomes of Iliac Artery Endovascular Therapy in the Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Diseases (K-VIS ELLA) Registry.

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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Long-term Clinical Outcomes and Prognostic Factors After Endovascular Treatment in Patients With Chronic Limb Threatening Ischemia.

BACKGROUND AND OBJECTIVES: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world 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. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Impact of aortic atheroma and distensibility on diastolic function and prognosis in patients with ischemic stroke.

BACKGROUND: Patients with ischemic stroke are vulnerable to heart failure with preserved ejection fraction (HFpEF) because these conditions share common risk factors. Although evaluation of the ascending aorta, aortic arch, and proximal descending thoracic aorta is an essential step to determine the source of the causative embolism, the relationship between the degree of aortic atheroma and left ventricular (LV) diastolic function has not been extensively investigated. METHODS: We analyzed the transesophageal and transthoracic echocardiography in ischemic stroke patients. Patients with previous coronary artery disease, valvular heart disease of more than moderate degree, and an LV ejection fraction of less than 50% were excluded. The relationships between the grade of the aortic atheroma, aortic stiffness indexes, and diastolic functional indexes were evaluated. RESULTS: In 295 patients, the atheroma grade was significantly correlated with aortic stiffness index, ratio of mitral annular and inflow velocities (E/e'), left atrial volume index, and LV diastolic elastance. With further adjustment for age, hypertension, diabetes, estimated glomerular filtration rate, left atrial volume index, and LV mass index, the significance of the atheroma grade was attenuated. In the subgroup analysis, the atheroma grade was significantly and independently related to E/e' in women (ß = 0.181, p = 0.032), but not in men. However, atheroma grade was not associated with poor clinical outcomes in either sex. CONCLUSIONS: Aortic atheroma grade was significantly and independently related to LV diastolic function, especially in women. This suggests that aortic atheroma is an index of arterial stiffness and a potential risk factor for HFpEF through ventricular-vascular interactions, especially in women.

Comparison of risk profiles for new-onset atrial fibrillation between patients aged <60 and ≥60 years.

BACKGROUND: Atrial fibrillation (AF) has a heterogeneous pathophysiology according to individual patient characteristics. This study aimed to identify the effects of widely known risk factors on AF incidence according to age and to elucidate the clinical implications of these effects. METHODS AND RESULTS: We analyzed data from 501,668 subjects (≥18years old) without AF and valvular heart disease from the Korean National Health Insurance Service-National Sample Cohort. The total population was divided into two groups according to age, <60years and ≥60years. AF occurred in 0.7% of the overall population (3,416 of 501,668) during the follow-up period (mean 47.6 months). In Cox regression analysis, age, male sex, previous ischemic stroke, heart failure, and hypertension were related to increased risk of new-onset AF in both age groups. Especially in the <60years age group, risk of new-onset AF was increased by relatively modifiable risk factors: obesity (body mass index ≥25kg/m2; hazard ratio[HR] 1.37 [1.22-1.55], p<0.001, interaction p<0.001), and hypertension (HR 1.93[1.69-2.22], p<0.001, interaction p<0.001). Although interactions were not significant, chronic obstructive pulmonary disease (HR 1.41[1.24-1.60], p<0.001) and chronic kidney disease (HR 1.28[1.15-1.41], p<0.001) showed increased trends of the risk of new-onset AF in the ≥60years age group. CONCLUSION: The risk profile for new-onset AF was somewhat different between the <60years and the ≥60years age groups. Compared to the ≥60years group, relatively modifiable risk factors (such as obesity and hypertension) had a greater impact on AF incidence in the <60years age group. Different management strategies to prevent AF development according to age may be needed.

Association between Body Mass Index and Clinical Outcomes of Peripheral Artery Disease after Endovascular Therapy: Data from K-VIS ELLA Registry.

BACKGROUND AND OBJECTIVES: Few studies have investigated the obesity paradox in clinical outcomes of peripheral artery disease (PAD). We investigated the association between body mass index (BMI) and clinical outcomes in PAD patients undergoing endovascular therapy (EVT). METHODS: Patients (n=2,914) from the retrospective Korean Vascular Intervention Society Endovascular Therapy in Lower Limb Artery Disease registry were categorized according to BMI: underweight (<18.5 kg/m², n=204), normal weight (18.5-25 kg/m², n=1,818), overweight (25-30 kg/m², n=766), or obese (≥30 kg/m², n=126). Groups were compared for major adverse cardiovascular events (MACE) and major adverse limb events (MALE). RESULTS: The underweight and obese groups were older and had more frequent critical limb ischemia and infrapopliteal artery disease than the normal or overweight groups (all p<0.001). Hypertension and diabetes were more frequent and current smoking was less frequent in the overweight and obese groups than the underweight or normal weight groups (all p <0.001). The underweight group showed the higher rates of MACE and MALE at 3 years (17.2%, 15.7%) compared with the normal weight (10.8%, 11.7%), overweight (8.4%, 10.7%), or obese groups (8.7%, 14.3%) (log-rank p<0.001, p=0.015). In contrast, the risk of MACE was lower in the overweight than the normal weight group (adjusted hazard ratio, 0.706; 95% CI, 0.537-0.928). CONCLUSIONS: In PAD patients undergoing EVT, underweight was an independent predictor for MACE and MALE, whereas MACE risk was lower for overweight than normal weight patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Korean Multicenter Registry Study of EPIC Stents for the Treatment of Iliac Artery Disease: K-EPIC Registry.

BACKGROUND AND OBJECTIVES: The EPIC™ stent is a self-expanding, nitinol stent that has been designed to enhance flexibility and provide expansion within vessels. The aim of the present study was to investigate the clinical efficacy and safety of the EPIC™ stent when used to treat iliac artery diseases in a prospective Korean multicenter registry. METHODS: A total of 138 patients with iliac artery diseases who received endovascular treatment with EPIC™ stents at 9 Korean sites were enrolled in a prospective cohort and followed for 1 year. The primary endpoint was the 1-year freedom from target lesion revascularization (TLR). The secondary endpoints were 1-year clinical patency and freedom from major adverse events (MAEs). RESULTS: The mean age of the study subjects was 66.8±8.5 years and most subjects were male (86.2%). The most frequent lesion type was Trans-Atlantic Inter-Society Consensus B (43.5%) and the majority (56.5%) of the target lesions were located in the common iliac artery. Procedural success was obtained in 99.3% of patients. The freedom from TLR and the clinical patency at 1-year follow-up were 94.9% and 92.3%, respectively. The 1-year rate of MAEs was 5.1%. Combined coronary artery disease (hazard ratio [HR], 5.91; 95% confidence interval [CI], 1.13-30.89; p=0.035) and smaller stent diameter (HR, 0.38; 95% CI, 0.17-0.88; p=0.023) were identified as independent risk factors of TLR after EPIC™ stent implantation. CONCLUSIONS: The EPIC™ stents demonstrated excellent immediate and 1-year efficacy and safety outcomes in iliac artery lesions in this multicenter, prospective, registry-based study.

Coronary calcification is associated with elevated serum lipoprotein (a) levels in asymptomatic men over the age of 45 years: A cross-sectional study of the Korean national health checkup data.

ABSTRACT: Lipoprotein a (Lp (a)) and coronary artery calcification (CAC) are markers of coronary artery and cardiovascular diseases. However, the association between Lp (a) and CAC in asymptomatic individuals remains unclear. In this study, we aimed to determine the influence of Lp (a) on CAC in asymptomatic individuals.We included 2019 asymptomatic Korean adults who underwent testing for a coronary artery calcium score (CACS) and Lp (a) at the Gangnam Severance Hospital Health Checkup Center in Korea from January 2017 to August 2019. Participants were divided into 2 groups: CACS = 0 and CACS > 0. Factors affecting the CACS were analyzed by sex. Because age is a major risk factor for atherosclerosis, ≥45 years in men and ≥55 years in women, we further divided participants into 4 subgroups (≥45 and <45 in men, ≥55 and <55 in women). Factors affecting the CACS in the 4 groups were analyzed.There was a positive correlation between the CACS and traditional cardiovascular risk factors. Lp (a) positively correlated with the CACS in men (P < .01) and remained significant after multivariable logistic regression (P < .01). The same result was observed in men aged ≥45 years (P < .01).Lp (a) is an independently associated factor of CAC and a marker of coronary atherosclerosis in asymptomatic men aged ≥45 years. In asymptomatic men aged ≥45 years, Lp (a) should be measured, and intensive Lp (a)-lowering treatment should be considered.

Effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis is an important prognostic factor in hypertrophic cardiomyopathy (HCM). However, the contribution from a wide spectrum of genetic mutations has not been well defined. We sought to investigate effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in HCM. METHODS: In 133 HCM patients, comprehensive genetic analysis was performed in 82 nuclear DNA (33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNA. In all patients, cardiovascular magnetic resonance (CMR) was performed, including 16-segmental thickness, late gadolinium enhancement (LGE), native and post-T1, extracellular volume fraction (ECV), and T2, along with echo-Doppler evaluations. RESULTS: Patients with sarcomere mutation (SM, n = 41) had higher LGE involved segment, % LGE mass, ECV and lower post-T1 compared to patients without SM (n = 92, all p < 0.05). When classified into, non-mutation (n = 67), only mitochondria-related mutation (MM, n = 24), only-SM (n = 36) and both SM and MM (n = 5) groups, only-SM group had higher ECV and LGE than the non-mutation group (all p < 0.05). In non-LGE-involved segments, ECV was significantly higher in patients with SM. Within non-SM group, patients with any sarcomere variants of uncertain significance had higher echocardiographic Doppler E/e' (p < 0.05) and tendency of higher LGE amount and ECV (p > 0.05). However, MM group did not have significantly higher ECV or LGE amount than non-mutation group. CONCLUSIONS: SMs are significantly related to increase in myocardial fibrosis. Although, some HCM patients had pathogenic MMs, it was not associated with an increase in myocardial fibrosis.

Effect of Renal and Left Ventricular Function on Serial Pulmonary Arterial Pressure Changes after Device Closure of Atrial Septal Defect.

BACKGROUND: The age of candidates for device closure of atrial septal defect (ASD) has been increasing. Thus, concerns exist about dyspnea aggravation or atrial fibrillation development after device closure due to augmentation of left ventricular (LV) and left atrial (LA) preload. This study aimed to examine patterns and determinants of serial pulmonary arterial pressure and left ventricular filling pressure changes after device closure of ASD. METHODS: Among the 86 consecutive patients who underwent percutaneous device closure of ASD, those with end-stage renal disease or those without pre- or postprocedural Doppler data were excluded. The clinical, transesophageal, and transthoracic echocardiographic findings of 78 patients were collected at baseline, one-day postprocedure, and one-year follow-up. RESULTS: The mean age of study patients was 49.8 ± 15.0 years, and the average maximal defect diameter and device size were 20.2 ± 6.0 mm and 23.8 ± 6.4 mm. Four patients (5.6%) underwent new-onset atrial fibrillation, and five patients (6.4%) took diuretics within one-year after closure. Some patients (n = 21; 27%) exhibited paradoxically increased tricuspid regurgitant velocity (TRV) one-day postprocedure; they also were older with lower e', glomerular filtration rate, and LV ejection fraction and a higher LA volume index. However, even in these patients, TRV deceased below baseline levels one-year later. Both E/e' and LA volume index significantly increased immediately after device closure, but all decreased one-year later. Larger defect size and higher TRV were significantly correlated with immediate E/e' elevation. CONCLUSION: In older, renal, diastolic, and systolic dysfunctional patients with larger LA and scheduled for larger device implantation, peri-interventional preload reduction therapy would be beneficial.

Development of a novel fluorescent biosensor for dynamic monitoring of metabolic methionine redox status in cells and tissues.

Aberrant production of reactive oxygen species (ROS) leads to tissue damage accumulation, which is associated with a myriad of human pathologies. Although several sensors have been developed for ROS quantification, their applications for ROS-related human physiologies and pathologies still remain problematic due to the unstable nature of ROS. Herein, we developed Trx1-cpYFP-fRMsr (TYfR), a genetically-encoded fluorescent biosensor with the remarkable specificity and sensitivity toward fMetRO (free Methionine-R-sulfoxide), allowing for dynamic quantification of physiological levels of fMetRO, a novel indicator of ROS and methionine redox status in vitro and in vivo. Moreover, using the sensor, we observed a significant fMetRO enrichment in serum from patients with acute coronary syndrome, one of the most severe cardiovascular diseases, which becomes more evident following percutaneous coronary intervention. Collectively, this study proposes that fMetRO is a novel biomarker of tissue damage accumulation in ROS-associated human pathologies, and that TYfR is a promising tool for quantifying fMetRO with potentials in versatile applications.