ABSTRACT: Background. Predictors of target lesion revascularization (TLR) have not been well defined in patients undergoing peripheral percutaneous interventions (PPI). In this study we analyze predictors of TLR in a consecutive cohort of patients from two medical centers. Methods. Data were extracted from a prospectively collected peripheral vascular registry. Of 105 consecutive patients (175 vessels) undergoing PPI, follow up was achieved in 104 patients (172 vessels) at 8.06 ± 4.51 months. Univariate analysis was performed between the groups with (n = 19, vessels = 25) and without (n = 85, vessels = 147) TLR. Logistic regression analysis was utilized to model for the predictors of TLR. Results. TLR occurred in 14% of vessels treated at 8.06 ± 4.51 months. By univariate analysis, vessels with TLR on follow up had longer treated segments (167.0 ± 139.16 mm vs. 98.49 ± 113.33 mm; p = 0.027), more severe lesions (91.96 ± 12.56% vs. 85.51 ± 14.43%; p = 0.037) and were younger (63.0 ± 10.1 years vs. 69.1 ± 11.1 years; p = 0.032). Also, there was a trend toward a higher hs-CRP (11.35 ± 17.85 vs. 7.45 ± 9.57 mg/L) and more total occlusions (44.0% vs. 22.6%) in the TLR group, but these did not reach statistical significance. Logistic regression analysis with backward elimination including all these variables showed that younger age (p = 0.007), female gender (p = 0.033) and treated vessel length (p = 0.028) were the only independent predictors of TLR. Conclusions. Younger age, female gender and longer treated vessel length are independent predictors of TLR in patients undergoing PPI. The cost-effectiveness in treating these patients with PPI versus surgery needs to be defined in future studies.
J INVASIVE CARDIOL 2009;21:266–269
Key words: Target lesion revascularization, peripheral intervention, femoropopliteal, clinical outcome
A high rate of restenosis remains the Achille’s heel of peripheral percutaneous intervention (PPI).1,2 In a meta-analysis of 1,003 patients undergoing PPI of the superficial femoral artery (SFA), the patency rate was 59% at 1 year, 52% at 3 years and 45% at 5 years.1 In the renal arteries, restenosis occurs up to 22 months after intervention.3
The mechanisms of restenosis in the periphery are likely to be different from the coronary vasculature, likely due to a higher burden of atherosclerosis, longer lesions, and a heightened inflammatory state in the peripheral vascular patient. Also, significant differences in blood flow rates and impedance in vascular beds between the heart and the skeletal muscle might be contributory reasons.4 In addition, inflammation markers increase significantly in certain peripheral arterial beds compared to others following PPI and a higher inflammatory response to PPI predicts a higher rate of restenosis.5–7
Several biomarkers of inflammation and coagulation were reported as predictors of restenosis in the periphery including high-sensitivity C-reactive protein (hs-CRP),8 fibrinogen,9 complement component C5a,10 D-dimer,11 baseline monocyte count12 and plasma tissue factor.13 These findings, however, are not consistent among all studies. Schillinger et al14 reported that restenosis post femoropopliteal angioplasty is related to post dilatation residual stenosis in the target segment (odds ratio 3.6, p = 0.001) and baseline C-reactive protein (CRP) (odds ratio 4.2; p = 0.02), but in their study, neither white blood cells nor fibrinogen levels were associated with restenosis.
Multiple clinical and angiographic predictors of restenosis post PPI have also been reported. These include limb ischemia and total occlusions,15 number of tibial runoff vessels,16,17 diabetes,11 lesion length,18 diffuse atherosclerotic cardiovascular disease or threatened limb loss.19 In this study, we evaluate the predictors of TLR in a cohort of consecutive patients undergoing PPI at our institution.
Methods
Data were extracted from a prospectively collected peripheral vascular registry at two medical centers. Consecutive patients with claudication (76%) or limb ischemia (24%) and who underwent PPI were included in the analysis. The registry tracks demographics, clinical, procedural and in-hospital outcome data on peripheral vascular patients in these 2 centers (Tables 1–3). In addition, all patients had an hs-CRP level measured as part of a routine preadmission testing (typically within a week of the procedure) for global risk assessment. Out-of-hospital follow up was achieved by phone calls and medical records. A standardized institutional review board (IRB)-approved script was utilized with phone calls. The study was approved by the IRB of each medical center.
Of 105 consecutive patients (175 vessels) undergoing PPI, follow up was achieved in 104 patients (172 vessels) at 8.06 ± 4.51 months. All patients who underwent follow up were included in the analysis. Also, a subgroup of patients followed for a minimum of 6 months (10.5 ± 2.7 months) (n = 74, 120 vessels) was separately analyzed. The primary endpoint of the study was target lesion revascularization (TLR). Secondary endpoints were target vessel revascularization and major adverse events that included death, stroke, major bleeding (loss of > 3 gm of hemoglobin with a source of bleed, retroperitoneal bleeding and/or intracranial bleeding), vascular access site complication (pseudoaneurysm or arteriovenous fistula), unplanned major amputation, and renal failure (rise of creatinine by > 0.5 from preprocedure levels).
Descriptive analysis was performed on all variables. Univariate analysis was performed between the groups with and without TLR. All angiographic variables that are vessel-specific (lesion severity, lesion length…) were analyzed by number of vessels in the denominator. Demographics and other variables that are patient-specific (such as age, gender…) were analyzed by number of patients in the denominator. Logistic regression analysis was utilized to model for the predictors of TLR.
Results
A total of 105 consecutive patients (175 vessels) who underwent PPI were included. Follow up was achieved in 104 patients (172 vessels) at 8.06 ± 4.51 months. Of these patients, 74 were followed for a minimum of 6 months (120 vessels) and were analyzed separately.
Table 1 describes the demographics, clinical and procedural variables of the cohort included in the analysis. Patients had a high baseline hs-CRP (8.17 ± 11.41) and a long treated segment (107.49 ± 119.10 mm). Of all vessels included, 35% had moderate-to-severe calcification, 25.4% were totally occluded, 9.8% had an angiographic thrombus and 77.7% were femoropopliteal. Almost half the patients were diabetic and 24% had limb ischemia.
TLR and target vessel revascularization (TVR) occurred in 14% and 16.3% of vessels, respectively at 8.06 ± 4.51 months. By univariate analysis, vessels with TLR on follow up had longer treated segments (167.0 ± 139.16 mm vs. 98.49 ± 113.33 mm; p = 0.027), more severe lesions (91.96 ± 12.56% vs. 85.51 ± 14.43%; p = 0.037) and were younger (63.0 ± 10.1 years vs. 69.1 ± 11.1 years; p = 0.032). Also there was a trend toward a higher h-CRP (11.35 ± 17.85 vs. 7.45 ± 9.57 mg/L) and more total occlusions (44.0% vs. 22.6%) in the TLR group, but these did not reach statistical significance. Logistic regression analysis with backward elimination including age, treated vessel length, lesion severity, gender, Rutherford Class (II–III versus IV–V), number of tibial runoff vessels and hs-CRP showed that younger age (p = 0.007), female gender (p = 0.033) and treated vessel length (p = 0.028) were the only independent predictors of TLR.
In the cohort of patients followed for at least 6 months, TLR and TVR occurred in 15.8% and 18.3% of vessels at 10.5 ± 2.7 months. A slight increase in TLR and TVR was seen with longer follow up, but logistic regression analysis continued to show that female gender (p = 0.029) and longer lesion length (p = 0.032) were the only independent predictors of TLR.
Discussion
In our study, lesion length was an independent predictor of TLR. Lesion length has been previously described as an important predictor of 5-year patency. Gallino et al18 reported predictors of 5-year patency of the arteries of the lower limbs post PPI in 411 patients (482 vessels). Patients with stenoses or occlusions 3 cm, or poor distal runoff had an elevated rate of reocclusion.
In contrast to Schillinger et al,14 hs-CRP was not a predictor of TLR in our study when controlling for lesion length and gender. Schillinger14 reported that restenosis post femoropopliteal angioplasty is related to baseline CRP (odds ratio 4.2; p = 0.02), but not white blood cells or fibrinogen. In their study, however, the primary endpoint was restenosis as assessed by oscillography, ankle brachial index, duplex sonography and angiography, rather than symptom-driven TLR, as in our cohort of patients. Also, in their studies, the mean length of the lesion treated was less than half the mean lesion length in our study (5 cm vs. 11.4 cm). Hs-CRP might be a strong predictor of restenosis in patients with shorter lesions, but does not appear to be an independent predictor of symptom-driven TLR in patients with excessively long lesions, as in our study. However, despite longer lesions, the overall TLR was relatively low in our patients and major adverse events were minimal (Table 2). Treatment of these long lesions is therefore feasible and safe.
In our study, female gender was also an independent predictor of TLR. This finding is consistent with several published reports indicating that female gender is a high risk for restenosis in carotid,20 iliac21 and femoropopliteal interventions.22 Several other studies, however, do not support this conclusion,23,24 which needs to be validated in a larger cohort of patients.
Study limitations. Our study is limited by its relatively small number of patients, but excellent overall follow up was achieved. Also, operator bias in treating patients might have influenced the TLR rate in the absence of predefined prospective criteria for reintervention. Furthermore, there were no set criteria for lesion revascularization in this study. The presence of claudication or limb ischemia, however, was the driving factor to retreat these patients, as asymptomatic patient were not treated in this cohort.
_________________________
From the Midwest Cardiovascular Research Foundation, Davenport, Iowa.
The authors report no conflicts of interest regarding the content herein.
Supported by the Nicolas and Gail Shammas Research Fund at the Midwest Cardiovascular Research Foundation.
Abstract presented at Transcatheter Cardiovascular Therapeutics (TCT) conference, Washington D.C., October 12–17, 2008.
Manuscript submitted December 8, 2008, provisional acceptance given February 4, 2009, final version accepted March 12, 2009.
Address for correspondence: Nicolas W. Shammas, MS, MD, Genesis Heart Institute, Cardiovascular Medicine, PC, 1236 E. Rusholme, Davenport, IA 52803. E-mail: shammas@mchsi.com
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