Different Lower Extremity Arterial Calcification Patterns in Patients with Chronic Limb-Threatening Ischemia Compared with Asymptomatic Controls.

OBJECTIVES: The most severe type of peripheral arterial disease (PAD) is critical limb-threatening ischemia (CLI). In CLI, calcification of the vessel wall plays an important role in symptoms, amputation rate, and mortality. However, calcified arteries are also found in asymptomatic persons (non-PAD patients). We investigated whether the calcification pattern in CLI patients and non- PAD patients are different and could possibly explain the symptoms in CLI patients. MATERIALS AND METHODS: 130 CLI and 204 non-PAD patients underwent a CT of the lower extremities. This resulted in 118 CLI patients (mean age 72 ± 12, 70.3% male) that were age-matched with 118 non-PAD patients (mean age 71 ± 11, 51.7% male). The characteristics severity, annularity, thickness, and continuity were assessed in the femoral and crural arteries and analyzed by binary multiple logistic regression. RESULTS: Nearly all CLI patients have calcifications and these are equally frequent in the femoropopliteal (98.3%) and crural arteries (97.5%), while the non-PAD patients had in just 67% any calcifications with more calcifications in the femoropopliteal (70.3%) than in the crural arteries (55.9%, p < 0.005). The crural arteries of CLI patients had significantly more complete annular calcifications (OR 2.92, p = 0.001), while in non-PAD patients dot-like calcifications dominated. In CLI patients, the femoropopliteal arteries had more severe, irregular/patchy, and thick calcifications (OR 2.40, 3.27, 1.81, p ≤ 0.05, respectively) while in non-PAD patients, thin continuous calcifications prevailed. CONCLUSIONS: Compared with non-PAD patients, arteries of the lower extremities of CLI patients are more frequently and extensively calcified. Annular calcifications were found in the crural arteries of CLI patients while dot-like calcifications were mostly present in non-PAD patients. These different patterns of calcifications in CLI point at different etiology and can have prognostic and eventually therapeutic consequences.

Arterial calcification and long-term outcome in chronic limb-threatening ischemia patients.

PURPOSE: Within five years after presentation 50-60% of patients with chronic limb-threatening ischemia (CLI) have died or had an amputation. We assessed the predictive value of lower extremity arterial calcification on computed tomography (CT) characteristics on both 7-years amputation-free survival and 10-years all-cause mortality in patients with CLI. METHOD: Included were 89 CLI patients (mean age 73.1 ±â€¯11.6 years) who underwent a CT angiography of the lower extremities. In the femoropopliteal and crural arteries based on a CT score the following calcification characteristics were assessed: severity, annularity, thickness and continuity. The predictive value of different arterial calcification characteristics was analysed by age- and sex-adjusted multivariate Cox regression analysis. RESULTS: Complete annular calcifications were common (femoropopliteal 43.7%, n = 38; crural, 63.2%, n = 55). Mean survival was 278.4 weeks (95% CI 238.77-318.0 weeks). Patients with complete annular calcifications had a higher all-cause 10-year mortality (femoropopliteal unadjusted HR 1.64, p = 0.04 and adjusted for age and sex HR 1.68, p = 0.04; crural unadjusted HR 1.92, p = 0.02, adjusted for age and sex HR 2.29, p = 0.006) than patients with other calcification characteristics. CONCLUSIONS: Annularity of calcification of both femoropopliteal and crural arteries is a predictor for 10-year all-cause survival, its hazard being even higher than the traditional prognostic risk factors for CLI and therefore could be involved in the poor survival of these patients.

10-Year Paclitaxel Dose-Related Outcomes of Drug-Eluting Stents Treated Below the Knee in Patients with Chronic Limb-Threatening Ischemia (The PADI Trial).

PURPOSE: Recently, two meta-analyses concluded that there appears to be an increased risk of long-term mortality of paclitaxel-coated balloons and stents in the superficial femoral and popliteal artery, and paclitaxel-coated balloons below the knee. In this post hoc study of the PADI Trial, we investigated the long-term safety of first-generation paclitaxel-coated drug-eluting stents (DES) below the knee and the dose-mortality relationships of paclitaxel in patients with chronic limb-threatening ischemia (CLI). MATERIALS AND METHODS: The PADI Trial compared paclitaxel-coated DES with percutaneous transluminal angioplasty with bail-out bare-metal stents (PTA ± BMS) in patients with CLI treated below the knee. Follow-up was extended to 10 years after the first inclusion, and survival analyses were performed. In addition, dose-related mortality and dose per patient weight-related mortality relations were examined. RESULTS: A total of 140 limbs in 137 patients were included in the PADI Trial. Ten years after the first inclusion, 109/137 (79.6%) patients had died. There was no significant difference between mortality in the DES group compared with the PTA ± BMS group (Log-rank p value = 0.12). No specific dose-related mortality (HR 1.00, 95% CI 0.99-1.00, p = 0.99) or dose per weight mortality (HR 1.05, 95% CI 0.93-1.18, p = 0.46) relationships were identified in the Cox-proportional Hazard models or by Kaplan-Meier survival analyses. CONCLUSIONS: There is a poor 10-year survival in both paclitaxel-coated DES and PTA ± BMS in patients with CLI treated below the knee. No dose-related adverse effects of paclitaxel-coated DES were observed in our study of patients with CLI treated below the knee. LEVEL OF EVIDENCE: The PADI Trial: level 1, randomized clinical trial.

CT calcification patterns of peripheral arteries in patients without known peripheral arterial disease.

PURPOSE: In the last few years histologic studies of peripheral arteries have shown that both intimal and medial calcifications are found in patients in an early, asymptomatic stage and that differentiation between medial and intimal calcifications is possible. The aim of this study was to assess the computed tomography (CT) calcification characteristics in peripheral arteries and to explore potential patterns in subjects without peripheral arterial disease (PAD). METHOD: Retrospectively, 204 patients without known PAD were studied. The thin slice CT-imaging characteristics severity, annularity, thickness and continuity were scored in the following arteries: plantar and dorsal, crural, femoro-popliteal, iliac and the abdominal aorta. Interrelation was assessed using linear regression and significance was tested by Chi-Square tests. RESULTS: In the crural arteries two calcification patterns with strong associations were found. Pattern 1: continuous-annular 93.5 % (29/31), continuous-thin and thin-annular both 73 % (27/37, p < 0.001) and pattern 2: thick-discontinuous 91.7 % (44/48), thick-dotted 68.8 % (33/48), patchy-dotted 59.3 % (16/27, p < 0.001). Similar associations were found in the femoro-popliteal artery, but not in the plantar, dorsal, iliac arteries and aorta. CONCLUSIONS: In the crural and femoropopliteal arteries at least two morphological patterns can be distinguished on CT that, compared to a CT-histologically validated score, may represent an intimal and medial calcification pattern.

Cost-Effectiveness of Drug-Eluting Stents for Infrapopliteal Lesions in Patients with Critical Limb Ischemia: The PADI Trial.

PURPOSE: Drug-eluting stents (DES) improve clinical and morphological long-term results compared to percutaneous transluminal angioplasty (PTA) with bailout bare metal stenting (BMS) in patients with critical limb ischemia (CLI) and infrapopliteal lesions (PADI trial). We performed a cost-effectiveness analysis of DES compared to PTA ± BMS in cooperation with Dutch health insurance company VGZ, using data from the PADI trial. MATERIALS AND METHODS: In the PADI trial, adults with CLI (Rutherford category ≥ 4) and infrapopliteal lesions were randomized to receive DES with paclitaxel or PTA ± BMS. Seventy-four limbs (73 patients) were treated with DES and 66 limbs (64 patients) with PTA ± BMS. The costs were calculated by using the mean costs per stent multiplied by the mean number of stents used per patient (€750 × 1.8 for DES vs €250 × 0.3 for PTA ± BMS). These costs were compared with the costs of major amputation (€16.000) and rehabilitation (first year €15.750, second year €7.375 and third year €3.600). RESULTS: The 5-year major amputation rate was lower in the DES group (19.3% vs 34.0% for PTA ± BMS; p = 0.091). In addition, the 5-year amputation-free survival and event-free survival were significantly higher in the DES group (31.8% vs 20.4%, p=0.043; and 26.2% vs 15.3%, p=0.041, respectively). After 1 year, the cost difference per patient between DES and PTA ± BMS is €1.679 in favor of DES and €2.694 after 3 years. CONCLUSION: In our analysis, DES are cost-effective due to the higher hospital costs of amputation and rehabilitation in the PTA ± BMS group. LEVEL OF EVIDENCE: Level 1b, analysis based on clinically sensible costs and randomized controlled trial.