Association between corrected QT interval and long-term cardiovascular outcomes in elderly patients who had undergone endovascular therapy for lower extremity arterial disease.

Background: Population-based studies have reported the association between prolonged corrected QT (QTc) intervals and an increased risk of adverse cardiovascular events. Data regarding the association between longer QTc intervals and incident cardiovascular outcomes in patients with lower extremity arterial disease (LEAD) are scarce. Objective: To examine the impact of QTc interval on long-term cardiovascular outcomes in elderly patients with symptomatic LEAD. Methods: This cohort study extracted data from the Tzu-chi Registry of ENDovascular Intervention for Peripheral Artery Disease (TRENDPAD) and enrolled 504 patients aged ≥ 70 treated with endovascular therapy for atherosclerotic LEAD from July 1, 2005, to December 31, 2019. The main outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE). Multivariate analysis was conducted using the Cox proportional hazard model to determine independent variables. We performed interaction analysis between corrected QT and other covariates and Kaplan-Meier analysis to compare the outcome of interest among the groups stratified by the tercile of QTc intervals. Results: A total of 504 patients [235 men (46.6%); mean age, 79.9 ± 6.2 years; mean QTc interval, 459 ± 33 msec] entered the final data analysis. We categorized the baseline patient characteristics according to terciles of QTc intervals. During the median follow-up time of 3.15 (interquartile ranges, 1.65-5.42) years, we noted 264 deaths and 145 MACEs. The 5-year rates of freedom from all-cause mortality (71% vs. 57% vs. 31%, P < 0.001) and MACEs (83% vs. 67% vs. 46%, P < 0.001) were significantly different among the tercile groups. Multivariate analysis showed that a 1-SD increase in the QTc interval increased the risk of all-cause mortality [hazard ratio (HR) 1.49, P < 0.001] and MACEs (HR 1.59, P < 0.001) after adjusting for other covariates. The interaction analysis showed that QTc interval and C-reactive protein levels were most strongly associated with death (HR = 4.88, 95% CI 3.09-7.73, interaction P < 0.001) and MACEs (HR = 7.83, 95% CI 4.14-14.79, interaction P < 0.001). Conclusions: In elderly patients with symptomatic atherosclerotic LEAD, a prolonged QTc interval is associated with advanced limb ischemia, multiple medical comorbidities, increased risk of MACEs, and all-cause mortality.

Repetition of Paclitaxel-Coated Devices for the Treatment of Lower Extremity Artery Disease: Mortality Outcomes and Predictors.

Background: A recent meta-analysis reported late excess mortality in patients treated with paclitaxel-coated devices (PCDs) for symptomatic femoropopliteal disease. However, this finding is controversial. Objectives: To investigate the impact on mortality and predictors of repeat exposure to PCDs in patients with lower extremity peripheral arterial disease (LE-PAD). Methods: We analyzed registry patient-level data from two centers. A total of 214 patients were enrolled, and stratified based on terciles of cumulative dose of paclitaxel. We treated 134 patients with a single PCD exposure and 80 with multiple PCD exposures. We used the follow-up index (FUI) in Kaplan-Meier survival estimates to minimize potential selection bias. We used Cox proportional hazard and splines models to determine the predictors of mortality and assess their relationships with mortality. Results: The mean cumulative dose of paclitaxel was significantly different among groups (6.40 mg vs. 15.06 mg vs. 38.57 mg, p < 0.001). The 5-year FUI (0.93 ± 0.19 vs. 0.94 ± 0.18 vs. 0.95 ± 0.15, p = 0.836) and survival rates were not different (65.4% vs. 51.9% vs. 72.0%, p = 0.148). There was no dose-response association between paclitaxel dosage and death (p = 0.297). The predictors of death were congestive heart failure, stroke, dialysis dependence, neutrophil-lymphocyte ratio (NLR) > 3, age > 71 years, and body mass index (BMI) < 20 kg/m2. Spline model analysis validated the non-linear associations between mortality, age, BMI, and NLR. Conclusions: Repeated PCD exposure for LE-PAD did not result in excess late mortality. Predictors of mortality might change over time, and continuous variables had non-linear relationships with death.

Pleiotropic Effects of APOB Variants on Lipid Profiles, Metabolic Syndrome, and the Risk of Diabetes Mellitus.

Apolipoprotein B (ApoB) plays a crucial role in lipid and lipoprotein metabolism. The effects of APOB locus variants on lipid profiles, metabolic syndrome, and the risk of diabetes mellitus (DM) in Asian populations are unclear. We included 1478 Taiwan Biobank participants with whole-genome sequence (WGS) data and 115,088 TWB participants with Axiom genome-wide CHB array data and subjected them to genotype-phenotype analyses using APOB locus variants. Five APOB nonsynonymous mutations, including Asian-specific rs144467873 and rs13306194 variants, were selected from participants with the WGS data. Using a combination of regional association studies, a linkage disequilibrium map, and multivariate analysis, we revealed that the APOB locus variants rs144467873, rs13306194, and rs1367117 were independently associated with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol levels; rs1318006 was associated with HDL cholesterol levels; rs13306194 and rs35131127 were associated with serum triglyceride levels; rs144467873, rs13306194, rs56213756, and rs679899 were associated with remnant cholesterol levels; and rs144467873 and rs4665709 were associated with metabolic syndrome. Mendelian randomization (MR) analyses conducted using weighted genetic risk scores from three or two LDL-cholesterol-level-associated APOB variants revealed significant association with prevalent DM (p = 0.0029 and 8.2 × 10-5, respectively), which became insignificant after adjustment for LDL-C levels. In conclusion, these results indicate that common and rare APOB variants are independently associated with various lipid levels and metabolic syndrome in Taiwanese individuals. MR analyses supported APOB variants associated with the risk of DM through their associations with LDL cholesterol levels.

Association Rule Mining and Prognostic Stratification of 2-Year Longevity in Octogenarians Undergoing Endovascular Therapy for Lower Extremity Arterial Disease: Observational Cohort Study.

BACKGROUND: Two-year longevity is a crucial consideration in revascularization strategies for patients with symptomatic lower extremity arterial disease (LEAD). However, factors associated with 2-year longevity and risk stratification in octogenarians or nonagenarians have been underreported. OBJECTIVE: This paper aims to investigate the associated variables and stratify the 2-year prognosis in older patients with LEAD. METHODS: We performed logistic regression and association rule mining based on the Apriori algorithm to discover independent variables and validate their associations with 2-year longevity. Malnutrition, inflammation, and stroke factors were identified. C statistics and Kaplan-Meier analysis were used to assess the impact of different numbers of malnutrition, inflammation, and stroke factors on 2-year longevity. RESULTS: We recruited a total of 232 octogenarians or nonagenarians (mean age 85 years, SD 4.2 years) treated with endovascular therapy. During the study period, 81 patients died, and 27 of those (33%) died from a cardiac origin within 2 years. Association rules analysis showed the interrelationships between 2-year longevity and the neutrophil-lymphocyte ratio (NLR) and nutritional status as determined by the Controlling Nutritional Status (CONUT) score or Geriatric Nutritional Risk Index (GNRI). The cut-off values of NLR, GNRI, and CONUT were ≥3.89, ≤90.3, and >3, respectively. The C statistics for the predictive power for 2-year longevity were similar between the CONUT score and the GNRI-based models (0.773 vs 0.760; P=.57). The Kaplan-Meier analysis showed that 2-year longevity was worse as the number of malnutrition, inflammation, and stroke factors increased from 0 to 3 in both the GNRI-based model (92% vs 68% vs 46% vs 12%, respectively; P<.001) and the CONUT score model (87% vs 75% vs 49% vs 10%, respectively; P<.001). The hazard ratio between those with 3 factors and those without was 18.2 (95% CI 7.0-47.2; P<.001) in the GNRI and 13.6 (95% CI 5.9-31.5; P<.001) in the CONUT score model. CONCLUSIONS: This study demonstrated the association and crucial role of malnutrition, inflammation, and stroke factors in assessing 2-year longevity in older patients with LEAD. Using this simple risk score might assist clinicians in selecting the appropriate treatment.

Contemporary cardiovascular outcomes in Taiwanese patients undergoing endovascular therapy for symptomatic lower extremity peripheral arterial disease.

BACKGROUND/PURPOSE: To investigate contemporary cardiovascular (CV) outcomes in Taiwanese patients with symptomatic low extremity peripheral artery disease treated with endovascular therapy. METHODS: An observational cohort study with up to 155 months of follow-up was conducted using a single-center registry database between July 2005 and June 2017. Long-term outcomes and predictors of future CV events were analyzed in 936 patients with 1246 affected legs. RESULTS: This study cohort comprised 21% claudicants and 79% critical limb ischemia (CLI) patients. Compared with claudicants, CLI patients had higher rates of medical comorbidities, tissue inflammation, and lesion complexities. During the study period, 349 patients died (130 CV deaths and 219 non-CV deaths), 306 had non-fatal CV events. The rates of 5-year freedom from all-cause mortality, major CV events (MACEs), and non-fatal CV events were 54.9%, 67.1%, and 56.6% respectively. For CLI patients, independent factors for all-cause mortality were age (odds ratio [OR] 1.03), atrial fibrillation (OR 1.79), albumin (OR 0.62), hematocrit (OR 0.96), body mass index (OR 0.94), C-reactive protein (OR 1.18), dialysis (OR 2.16), and non-ambulance (OR 2.05). Congestive heart failure, dialysis, and non-ambulance independently predicted the MACEs (OR 2.04, 1.93, and 1.67, respectively). For claudicants, coronary artery disease (CAD) was the essential factor for all-cause mortality (OR 2.24), MACE (OR 2.76) and non-fatal CV events (OR 1.82). CONCLUSION: Long-term survival and MACE-free rates were significantly worse in CLI patients than in claudicants. Malnutrition and inflammation were associated with long-term survival. CAD, low hematocrit, dialysis, CHF, and ambulatory status predicted future CV events.

Risk stratification for low extremity amputation in critical limb ischemia patients who have undergone endovascular revascularization: A survival tree analysis.

Patients with peripheral artery disease (PAD) are a heterogeneous population and differ in risk of mortality and low extremity amputation (LEA), which complicates clinical decision-making. This study aimed to develop a simple risk scale using decision tree methodology to guide physicians in managing critical limb ischemia (CLI) patients who will benefit from endovascular therapy (EVT).A total of 736 patients with CLI, Rutherford classification (RC) stage ≥4, and prior successful EVT were included. Variables significantly associated with LEA by univariate analysis (P < .05) were selected and put into classification tree analysis using the Classification and Regression Tree (CART) model with a dependent variable, amputation, and depth of tree = 3. Four risk groups were generated according to the order of amputation rate. The amputation-free survival (AFS) times between groups were compared using the Kaplan-Meier curve with the log-rank test.Patients were classified as high risk for amputation (G4) (WBC counts ≥10,000/µl, and platelet-lymphocyte ratio (PLR) ≥130.337); intermediate risk group 1 (G3) (WBC < 10,000/µl and RC stage before EVT > 5); intermediate risk group 2 (G2) (WBC count ≥ 10,000/µl, and PLR < 130.337) and low-risk group (G1) (WBC < 10,000/µl, RC before EVT ≤ 5). G2, G3, and G4 risk groups had shorter AFS time (range, 58.7 to 65.5 months) than the G1 risk group (100 months) (P < .05). Risk of LEA was significantly higher in the G4, G3, and G2 groups than in the G1 group (P ≤ .05). The G4 group had the highest risk of amputation (odds ratio = 6.84, P < .001).This simple risk scale model can help healthcare professionals more easily identify and appropriately treat patients with CLI who are at different levels of risk for LEA following endovascular revascularization.

Feasibility and Mid-Term Outcomes of Drug-Coated Balloon Angioplasty Between Intermittent Claudication and Critical Limb Ischemia in Patients with Femoropopliteal Disease.

BACKGROUND: The efficacy of drug-coated balloons (DCBs) in critical limb ischemia (CLI) is unclear. To investigate the clinical characteristics and outcomes of DCBs in symptomatic femoropopliteal disease between patients with intermittent claudication (IC) and CLI. METHODS: Data were retrospectively collected from three centers in Taiwan on patients who received DCBs for femoropopliteal lesions between March 2013 and June 2017. We compared the clinical characteristics and outcomes regarding binary restenosis, amputation-free survival (AFS), and major adverse limb events (MALEs) between groups. Cox proportional hazards analysis was used to identify predictors of outcome endpoints. RESULTS: We enrolled a total of 200 affected limbs in 174 patients, including 83 limbs in 71 patients with IC and 117 limbs in 103 patients with CLI. Compared to the patients with claudication, those with CLI were older and had higher proportions of medical comorbidities, tissue inflammation, poor runoff, and vessel calcification. The 3-year rates of freedom from binary restenosis (57% vs. 59%, p = 0.781), and MALEs (77% vs. 67%, p = 0.507) were similar between the two groups. However, the 3-year AFS was significantly higher in the IC group compared to the CLI group (91% vs. 73%, p = 0.001). Lesion length and severe calcification independently predicted binary restenosis, and restenotic lesion predicted MALEs. Age, congestive heart failure, and dialysis were independently associated with AFS. CONCLUSIONS: Despite advanced limb ischemia and comorbidities, the mid-term outcomes in surviving CLI patients were similar to those in the IC patients after treatment with DCBs for femoropopliteal disease.