Hsuan-Li Huang

Dual vascular access for critical limb ischemia: immediate and follow-up results.

Purpose: To describe a procedural technique involving a combined antegrade femoral and retrograde tibial approach for treatment of complex popliteal and infrapopliteal occlusions, and to determine the safety and efficacy of this technique. Materials and Methods: From May 2008 to March 2010, seven patients presenting with critical limb ischemia received dual vascular access intervention in this institution. Five legs were treated via the retrograde tibial approach after failure of antegrade intervention. A dual access approach was planned and adopted in another two legs. The target vessels were located at popliteal or infrapopliteal arteries. Results: We successfully gained all retrograde tibial access sites and achieved 100% procedural success and immediate hemodynamic improvement. Five legs required stent implantation to optimize the procedural results. No major complication occurred at the tibial access site. During the follow‐up period (11.3 ± 7.2, range 3–23 months), no patients required any major amputation; only one patient underwent a mid‐foot amputation. The target vessel revascularization rate at 3 and 6 months was 0 and 28.6%, respectively. Conclusion: Dual vascular access was successfully used in a small number of selected patients and this technique may hold promise in improving the success rates in the treatment of complex popliteal and infrapopliteal occlusions.

Feasibility and Clinical Outcomes of Peripheral Drug-Coated Balloon in High-Risk Patients with Femoropopliteal Disease

Background Clinical outcomes of the drug-coated balloon (DCB) procedure in high-risk patients with femoropopliteal (FP) disease have not been investigated sufficiently. Methods This retrospective, single-center study analyzed 87 patients (39% dialysis) and 97 affected legs (64% critical limb ischemia [CLI]) that underwent DCB for symptomatic FP disease from March 2013 to September 2014. Risk stratification was based on FeDCLIP (female, diabetes, dialysis, CLI, lesion length >150 mm and poor runoff) score. The DCB outcomes among the different risk groups were compared and factors predicting restenosis were analyzed during follow-up. Results Most of study participants (84%) were moderate to high-risk patients. The procedural success rate was 100% and the 30-day major adverse vascular event rate was 2.1%. The mean lesion length was 178 ± 106 mm and the mean follow-up time was 428 ± 145 (range 50–782) days. The binary restenosis-free and clinically driven target lesion revascularization (CD-TLR)-free rates at 12 months were 77.5% and 84.3%, respectively, for all participants. No significant differences were observed in 1-year binary restenosis and CD-TLR rates in the low-, moderate-, and high-risk groups (60%, 84%, and 73%: p = 0.396; 78%, 89%, and 80%: p = 0.635, respectively). In multivariate analysis, lesion length >150 mm (Hazard ratio [HR]: 8.00, 95% confidence interval (CI) 1.12 to 55.6, p = 0.038) and Rutherford class 6 (HR: 7.09, 95% CI, 1.15 to 43.5, p = 0.034) were identified as independent predictors of binary restenosis. Conclusions Despite general comorbidities and advanced limb ischemia, 1-year outcomes of DCB in high-risk patients with FP disease were effective. The DCB procedure holds promise to improve vessel patency; however, lesion length >150 mm and major tissue loss were independent predictors for binary restenosis after the treatment.

Circulating YKL-40 Level, but not CHI3L1 Gene Variants, Is Associated with Atherosclerosis-Related Quantitative Traits and the Risk of Peripheral Artery Disease

YKL-40, a pleotropic cytokine, is emerging as a risk factor and a prognostic predictor of atherosclerotic cardiovascular disease. We attempted to elucidate the genetic, clinical and biochemical correlates of circulating YKL-40 level and, by combining it with CHI3L1 gene variants, with the risk and long-term mortality of peripheral artery disease (PAD). Plasma YKL-40 concentrations were measured in 612 Taiwanese individuals who had no clinically overt systemic disease. Clinical parameters, CHI3L1 gene promoter variants and 18 biomarker levels were analyzed. Eighty-six PAD patients were further enrolled for analysis. Significant associations were found between CHI3L1 genotypes/haplotypes and YKL-40 levels for the health examination subjects (smallest p = 8.36 × 10−7 for rs4950928 and smallest p = 1.72 × 10−10 for haplotype TGG) and also for PAD patients. For the health examination subjects, circulating YKL-40 level, but not CHI3L1 gene variants, were positively associated with age, smoking, and circulating levels of triglyceride, lipocalin 2 and multiple inflammatory biomarkers and negatively associated with low-density-lipoprotein cholesterol levels. Circulating YKL-40 level is also significantly associated with the risk of PAD (p = 3.3 × 10−23). Circulating YKL40 level, but not CHI3L1 gene promoter variants, is associated with the risk of PAD in Taiwanese. The association of YKL-40 levels with multiple quantitative traits relating to the risk of PAD may provide a molecular basis linking YKL-40 to atherosclerotic cardiovascular disease.

Clinical predictors of long-term outcomes in patients with critical limb ischemia who have undergone endovascular therapy.

Clinical predictors of long-term outcomes in patients with critical limb ischemia (CLI) treated with endovascular therapy (EVT) remain unclear. In this study, clinical predictors of long-term outcomes in EVT-treated patients with CLI were investigated. In this prospective, observational study, we analyzed a total of 253 Taiwanese patients with CLI with 314 limbs who underwent EVT between 2005 and 2012. Cox models were used to estimate hazard ratios of death, limb loss, and sustained clinical success (SCS). Multivariate analysis showed that age, atrial fibrillation (AF), end-stage renal disease (ESRD), and albumin were significant predictors of mortality. Patients with coronary artery disease and low albumin levels had a significant risk of major limb amputation, while AF, ESRD, and albumin were significant, independent predictors of SCS. In addition to previously reported predictors, we showed that AF and malnutrition can be used to predict long-term outcome in EVT-treated patients with CLI.

Growth Differentiation Factor 15 May Predict Mortality of Peripheral and Coronary Artery Diseases and Correlate with Their Risk Factors

Plasma GDF15 concentrations were measured in 612 Taiwanese individuals without overt systemic disease. Clinical parameters, GDF15 genetic variants, and 22 biomarker levels were analyzed. We further enrolled 86 patients with PAD and 481 patients with CAD, who received endovascular intervention and coronary angiography, respectively, to examine the role of GDF15 level in predicting all-cause mortality. Significant associations were found between GDF15 genotypes/haplotypes and GDF15 levels. The circulating GDF15 level was positively associated with age, smoking, hypertension, and diabetes mellitus as well as circulating levels of lipocalin 2 and various biomarkers of inflammation and oxidative stress. Kaplan-Meier survival analysis showed that baseline GDF15 levels of above 3096 pg/mL and 1123 pg/mL were strong predictors of death for patients with PAD and CAD, respectively (P = 0.011 and P < 0.001). GDF15 more accurately reclassified 17.3% and 29.2% of patients with PAD and CAD, respectively (P = 0.0046 and P = 0.0197), compared to C-reactive protein. Both genetic and nongenetic factors, including cardiometabolic and inflammatory markers and adipokines, were significantly associated with GDF15 level. A high level of GDF15 was significantly associated with an increase of all-cause mortality in patients with high-risk PAD and in patients with angiographically documented CAD.

Genetic variants associated with circulating MMP1 levels near matrix metalloproteinase genes on chromosome 11q21-22 in Taiwanese: interaction with obesity

BackgroundMMP1 is implicated in the pathogenesis of atherothrombotic cardiovascular disease. We aimed to elucidate genetic determinants of inflammatory marker levels, including circulating MMP1, in Taiwanese, and their association with obesity.MethodsFive genetic polymorphisms around matrix metalloproteinase genes on chromosome 11q21-22 region were genotyped in 519 subjects.ResultsAfter adjusting for clinical covariates, two polymorphisms were significantly associated with MMP1 levels, rs1799750 and rs495366, using an additive inheritance model (P = 1.5x10-4 and P = 2.57x10-5, respectively). Using dominant model, minor alleles of rs1799750 and rs495366 were associated with higher MMP1 levels (P = 1.3x10-4 and P = 1.95x10-5, respectively). In haplotype analysis, two haplotypes inferred from five SNPs (A2GATA and A1GATG) were associated with MMP1 levels (P = 5x10-4 and P = 8.47x10-5, respectively). Subgroup and interaction analysis revealed an association of rs1799750 and rs495366 with MMP1 levels only in non-obese subjects (P = 6.66x10-6 and P = 4.38x10-5, respectively, and interaction P = 0.008 for rs1799750). Haplotype interaction analysis also showed significant interaction for haplotype A1GATG (interaction P = 0.003).ConclusionsGenotypes/haplotypes around MMP1 locus are associated with MMP1 levels in Taiwanese. Further, since genotypes/haplotypes near MMP1 locus interact with obesity to set MMP1 levels, genetic determinants for MMP1 level may be different between obese and non-obese individuals.

Endovascular intervention in Taiwanese patients with critical limb ischemia: Patient outcomes in 333 consecutive limb procedures with a 3-year follow-up

BACKGROUND/PURPOSE Midterm outcomes of endovascular intervention (EVI) for critical limb ischemia (CLI) have not been previously reported in Taiwan. This study assessed the safety, feasibility, and patient-oriented outcomes for CLI patients after EVI. METHODS From June 2005 to December 2011, 270 patients underwent EVI for CLI of 333 limbs. Primary patency (PP), assisted primary patency (AP), limb salvage, sustained clinical success (SCS), secondary SCS (SSCS), and survival were assessed using Kaplan-Meier analysis. RESULTS The procedural success rate was 89%, and the periprocedural mortality and major complication rates within 30 days were 0.6% and 6.9%, respectively. During the mean follow-up time of 27 ± 20 months (1-77), 64 patients died and 25 legs required major amputation. Eighty-one percent of the patients with tissue loss had wound healing at 6 months and 75% of the patients were ambulatory, with or without assisting devices, at 1 year. The overall survival and limb salvage rates at 3 years were 70% and 90%, respectively. The PP and AP at 1 and 3 years were 58% and 37% and 79% and 61%, respectively. The SCS and SSCS were 65% and 46% and 80% and 64% at 1 and 3 years, respectively. CONCLUSION In Taiwan, EVI was a safe and feasible procedure for CLI patients, with a high procedural success rate and lower complication rate. Sustained limb salvage and clinical success can be afforded with an active surveillance program and prompt intervention during midterm follow-up.

Activin A Predicts Left Ventricular Remodeling and Mortality in Patients with ST-Elevation Myocardial Infarction.

BACKGROUND Activin A levels increase in a variety of heart diseases including ST-elevation myocardial infarction (STEMI). The aim of this study is to investigate whether the level of activin A can be beneficial in predicting left ventricular remodeling, heart failure, and death in patients with ST-elevation myocardial infarction (STEMI). METHODS We enrolled 278 patients with STEMI who had their activin A levels measured on day 2 of hospitalization. Echocardiographic studies were performed at baseline and were repeated 6 months later. Thereafter, the clinical events of these patients were followed for a maximum of 3 years, including all-cause death and readmission for heart failure. RESULTS During hospitalization, higher activin A level was associated with higher triglyceride level, lower left ventricular ejection fraction (LVEF), and lower left ventricular end diastolic ventricular volume index (LVEDVI) in multivariable linear regression model. During follow-up, patients with activin A levels > 129 pg/ml had significantly lower LVEF, and higher LVEDVI at 6 months. Kaplan-Meier survival curves showed that activin A level > 129 pg/ml was a predictor of all-cause death (p = 0.022), but not a predictor of heart failure (p = 0.767). CONCLUSIONS Activin A level > 129 pg/ml predicts worse left ventricular remodeling and all-cause death in STEMI.

Clinical Outcomes of Repetition of Drug-Coated Balloon for Femoropopliteal Restenosis After Drug-Coated Balloon Treatment

BACKGROUND To compare the clinical outcomes of patients undergoing repeated drug-coated balloon (DCB) treatment for femoropopliteal (FP) DCB restenosis with those of patients without repetition-DCB.Methods and Results:From March 2013 to September 2014, 102 patients (118 affected legs) underwent DCB for symptomatic FP disease; 47 patients had restenosis, and 37 underwent reintervention over a 45-month follow-up. We compared the outcomes of repetition-DCB for DCB restenosis with those of patients without repetition. The baseline patient and lesion characteristics were similar between groups. The mean lesion length was 200.8±113.1 and 195.2±134.6 mm, P=0.894, respectively. In addition, the procedural and follow-up outcomes were not different. The rates of freedom from binary restenosis (70% vs. 14%, P=0.001) and clinically driven target lesion revascularization (CD-TLR) (78% vs. 38%, P=0.026) at 1 year were statistically different between groups. Cox regression analysis showed that repetition of DCB was the only predictor for freedom from binary restenosis (hazard ratio [HR]: 6.15, 95% confidence interval (CI) 1.60 to 23.6, P=0.008) and CD-TLR (HR: 5.37, 95% CI 1.32-22.0, P=0.019). CONCLUSIONS For FP DCB restenosis, repetition of DCB can potentially improve vessel patency and significantly reduce the need for reintervention compared with conventional treatment. However, these observations require further confirmation in larger scale studies.

Outcomes of Endovascular Therapy With the Controlled Antegrade Retrograde Subintimal Tracking (CART) or Reverse CART Technique for Long Infrainguinal Occlusions

Purpose: To compare the safety, efficacy, and clinical outcomes associated with the controlled antegrade retrograde subintimal tracking (CART) or reverse CART (r-CART) technique to the conventional retrograde approach in the treatment of patients with long infrainguinal occlusions. Methods: From May 2008 to April 2014, 121 patients failed antegrade recanalization and underwent a retrograde approach to recanalize long infrainguinal occlusions. Patients who underwent successful endovascular therapy (EVT) by the conventional retrograde approach (CRA group) were compared to patients who had successful EVT using the CART/r-CART technique (CART group) after failure of a bidirectional approach. The efficacy, safety, vessel patency, and other clinical outcomes were compared between the groups. Results: Fifty-eight patients (mean age 71.6±12.2 years; 32 men) underwent successful EVT (47.9%, 58/121) using the conventional retrograde approach (CRA group), while 44 patients (mean age 70.8±11.1 years; 31 men) among the 50 patients who underwent the CART/r-CART technique were successfully treated (88.0%, 44/50). Both groups had similar average occlusion lengths and gained 100% immediate hemodynamic success after EVT. There was no significant difference between the groups regarding procedure-related complications. During follow-up, 28 patients died (p=0.380), but there were no differences in the rates of major (p=0.279) or minor amputation (p=0.417) between the groups. There was no difference in the 2-year primary patency (31% vs 24%, p=0.686), assisted primary patency (66% vs 76%, p=0.251), target vessel revascularization (65% vs 54%, p=0.845), or sustained clinical success (52% vs 46%, p=0.995) rates between the CRA and CART groups, respectively. Conclusion: Based on acceptable safety, efficacy, and follow-up results in this study, the CART/r-CART technique can salvage patients with long peripheral occlusions after failure of the conventional antegrade or retrograde approach.