Felix Mahler

Nitinol Stent Implantation Versus Percutaneous Transluminal Angioplasty in Superficial Femoral Artery Lesions up to 10 cm in Length: The Femoral Artery Stenting Trial (FAST)

Background— Endoluminal treatment of superficial femoral artery lesions is a matter of controversy. The present study was designed to investigate the impact of nitinol stenting of superficial femoral artery lesions with a maximum length of 10 cm on restenosis and clinical outcomes at 1 year. Methods and Results— Two hundred forty-four patients (168 men; 66±9 years) with a single superficial femoral artery lesion and chronic limb ischemia were randomized to implantation of a single Bard Luminexx 3 stent (123 patients) or stand-alone percutaneous transluminal angioplasty (PTA) (121 patients). Mean lesion length was 45 mm. Technical success (residual stenosis <50% for PTA, <30% for stenting) was achieved in 96 patients assigned to PTA (79%) and 117 patients assigned to stenting (95%); 13 PTA group patients (11%) “crossed over” to stenting. At 1 year, the primary end point of ultrasound-assessed binary restenosis was reached in 39 of 101 PTA group patients (38.6%) and 32 of 101 stent group patients (31.7%; absolute treatment difference, −6.9%; 95% CI, −19.7% to 6.2%; P=0.377). Target lesion revascularization rates at 1 year were 18.3% and 14.9%, respectively (absolute treatment difference, −3.3%; 95% CI, −13.0% to 6.4%; P=0.595). No statistically significant difference between treatment groups was observed at 12 months in the improvement by at least 1 Rutherford category of peripheral arterial disease. Conclusions— In the present study of patients with short superficial femoral artery lesions, the hypothesized absolute difference of 20% in binary restenosis at 1 year between the implantation of a single Luminexx nitinol stent and stand-alone PTA could not be demonstrated. A smaller difference requiring a larger trial might have been missed.

Pharmacologic and Hemodynamic Influences on the Rate of Isovolumic Left Ventricular Relaxation in the Normal Conscious Dog

We studied the effects of acute pharmacologic and hemodynamic interventions on isovolumic left ventricular relaxation in 19 conscious dogs using micromanometer tip catheters. Isoproterenol (11 studies) augmented peak rate of rise of left ventricular pressure [(+) dP/dt] by 1,275+/-227 (SE) mm Hg/s (P < 0.001) and dP/dt at an isopressure point of 35 mm Hg during isovolumic relaxation [(-) dP/dt(35)] by 435+/-80 mm Hg/s (P < 0.001). Peak (-) dP/dt decreased by 467+/-89 mm Hg/s (P < 0.002). The time constant, T, derived from the logarithmic fall of pressure during isovolumic relaxation, shortened from 20+/-2.8 to 14.9+/-1.8 ms (P < 0.003). Calcium (11 studies) increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.0001); peak (-) dP/dt was unchanged. T shortened from 20.4+/-1.8 to 17.3+/-1.5 ms (P < 0.002). Volume (13 studies) did not affect either dP/dt or T. Phenylephrine (13 studies) augmented peak (-) dP/dt, but reduced (-) dP/dt(35) (both P < 0.01); T lengthened from 22.1+/-1.5 to 32.5+/-1.5 ms (P < 0.01). In 15 studies, rapid atrial pacing increased peak (+) dP/dt and (-) dP/dt(35) (both P < 0.01). In the first post-pacing beat, peak (-) dP/dt and (-) dP/dt(35) decreased (both P < 0.01), although peak (+) dP/dt increased further. T paralleled values of (-) dP/dt(35). In five dogs, beta adrenergic blockade had no significant effect on any variable after calcium, volume, or phenylephrine infusion or during or after atrial pacing when the pre-and post-propranolol states were compared. We conclude that positive inotropic interventions augment both left ventricular contraction and relaxation. The changes in isovolumic relaxation are independent of alterations in sympathetic tone produced by beta-adrenergic blockade. Peak (-) dP/dt may not be a valid measure of left ventricular relaxation rate during acute alterations in inotropic state or afterload.

17β-Estradiol inhibits proliferation and migration of human vascular smooth muscle cells: similar effects in cells from postmenopausal females and in males

Objectives: Cardiovascular disease is rare in premenopausal women, but increases after the menopause when hormone replacement therapy reduces coronary events. Vascular smooth muscle cell (SMC) proliferation and migration occur in atherosclerosis, restenosis and venous graft disease. We studied the effects of 17β-estradiol on SMC proliferation and migration. Methods: SMC were cultured from saphenous veins of postmenopausal women and age-matched men. Cell growth was determined by 3H-thymidine incorporation and cell counting. Migration of SMC was assessed in 4-well chambers. SMC were seeded in one corner and PDGF-BB in filter paper glued onto the opposite wall. Results: PDGF-BB (5 ng/ml for 24 h) similarly stimulated 3H-thymidine incorporation in female (511 ± 57%; n = 8) and male (528 ± 62%; n = 12) SMC. This was reduced by 17β-estradiol (10−8–10−6 M; female 313 ± 52%; male 337 ± 54%; P < 0.05). PDGF-BB increased the number of SMC ( P < 0.0001 at 10 days) obtained from females (153 ± 3%; n = 5) and males (150 ± 4%; n = 5), which was inhibited by 17 β-estradiol (10−6 M; female 134 ± 7%; male 128 ± 5%; P < 0.05). Similar results were obtained with basic fibroblast growth factor. In contrast to 17β-estradiol, another steroid (dexamethasone) had no effects on 3H-thymidine incorporation in these cells stimulated with PDGF-BB. PDGF-BB (0.01–1 ng) stimulated SMC migration ( P < 0.05) which was inhibited by 17β-estradiol (10−10–10−6 M; n = 5; P < 0.005). Conclusion: 17β-Estradiol inhibits growth-factor-induced SMC proliferation and migration regardless of gender. These effects of 17β-estradiol may contribute to its cardiovascular protective properties in postmenopausal women during replacement therapy.

Effects of Percutaneous Transluminal Angioplasty and Endovascular Brachytherapy on Vascular Remodeling of Human Femoropopliteal Artery by Noninvasive Magnetic Resonance Imaging

Background—Percutaneous transluminal angioplasty (PTA) of severely stenotic peripheral vascular lesions is hampered by a higher restenosis rate. The effects of PTA on vascular wall as well as the effects of the antirestenotic properties of endovascular brachytherapy (EVBT) remain unclear. MRI allows in vivo noninvasive assessment of the vascular effects of such treatment strategies. We sought to elucidate the vascular effect of PTA and PTA+EVBT by serial MRI. Methods and Results—Twenty symptomatic patients with severe stenosis of the femoropopliteal artery were randomly assigned to PTA (n=10) or PTA+EVBT (n=10; 14 Gy by &ggr;-irradiation source) and imaged by high-resolution MRI before and 24 hours and 3 months after intervention. An independent observer blinded to the procedure analyzed the MRI data. At 24 hours, cross-sectional MRI revealed that lumen area (86% and 67%) and total vessel area (47% and 34%) increased similarly in the PTA and PTA+EVBT groups, respectively. All patients showed severe splitting of the atherosclerotic plaque, resulting in an irregularly shaped lumen. At 3 months, MRI revealed a significant difference in lumen area change between the PTA and PTA+EVBT groups (40% and 106%, respectively; P=0.026) and in the total vessel area (14% and 39%, respectively; P=0.018). At 3 months, plaque disruption was still present in 50% of the patients treated with PTA+EVBT. Conclusions—After PTA, there is deep disruption of the atherosclerotic plaques and an extensive remodeling process of the arterial wall. Luminal loss after PTA is partially due to inward vessel remodeling. Brachytherapy prevents inward remodeling and induces an increase in lumen area but partially prevents healing of disrupted vessel surface.

Late acute thrombotic occlusion after endovascular brachytherapy and stenting of femoropopliteal arteries

OBJECTIVES The aim of this article is to underline the importance of this complication after endovascular brachytherapy (EVBT) and intravascular stenting of the femoropopliteal arteries occurring in a running randomized trial. BACKGROUND Endovascular brachytherapy has been proposed as a promising treatment modality to reduce restenosis after angioplasty. However, the phenomenon of late acute thrombotic occlusion (LATO) in patients receiving EVBT after stenting is of major concern. METHODS In an ongoing prospective multicenter trial, patients were randomized to undergo EVBT (iridium 192; 14 Gy at a depth of the radius of the vessel +2 mm) after percutaneous recanalization of femoropopliteal obstructions. Of the 204 patients who completed the six months follow-up, 94 were randomized to EVBT. RESULTS Late acute thrombotic occlusion occurred exclusively in 6 of 22 patients (27%) receiving EVBT after intravascular stenting and always in concomitance with reduction of antithrombotic drug prevention (clopidogrel). Conversely, none of the 13 patients with stents and without EVBT (0%; p < 0.05) and none of the 72 patients (0%; p < 0.01) undergoing EVBT after simple balloon angioplasty presented LATO. CONCLUSIONS Late thrombotic occlusion occurs not only in patients undergoing EVBT after percutaneous coronary recanalization but also after stenting of the femoropopliteal arteries and may compromise the benefits of endovascular radiation. The fact that all our cases with LATO occurred concomitantly with stopping clopidogrel may indicate a possible rebound mechanism. An intensive and prolonged antithrombotic prevention is probably indicated in these patients.

Does deep femoral artery revascularization as an isolated procedure play a role in chronic critical limb ischemia

Purpose: To prospectively evaluate the midterm outcome after balloon angioplasty or surgical profundaplasty of the deep femoral artery (DFA) as an isolated procedure in chronic critical limb ischemia (CLI). Methods: Between 1995 and 2001, 21 limbs in 20 patients (mean age 77±8 years) were treated by revascularization of the deep femoral artery (DFA) as an isolated procedure for limb salvage. All patients had long-segment femoropopliteal occlusions unsuitable for revascularization and critical obstruction of the DFA. Clinical outcome was assessed at 1, 3, 6, and 12 months. Clinical treatment efficacy was defined as resolved CLI in surviving patients without major amputation after isolated DFA revascularization. Repeat target limb revascularization, major amputation, and death were solitary study endpoints; survival analyses were performed using the Kaplan-Meyer method. Results: Angioplasty with or without stenting was performed in 14 (67%) limbs and surgical profundaplasty in 7 (33%) limbs, with a technical success rate of 100%. Clinical treatment efficacy was 25% at 12 months; the cumulative rates of repeat target limb revascularization, major amputation, and death were 49%, 36%, and 55%, respectively. Major amputation and persistent CLI dominated in patients with stage IV disease (89%), whereas rest pain resolved in the majority of patients with stage III disease (67%; p<0.05). Conclusions: Isolated DFA revascularization seems insufficient to support wound healing in CLI, but might be a treatment option in CLI patients with rest pain.

Endovascular brachytherapy after femoropopliteal balloon angioplasty fails to show robust clinical benefit over time.

Purpose: To determine if the short-term efficacy of adjunctive endovascular brachytherapy (EVBT) is maintained over time in patients undergoing balloon angioplasty (BA) of femoropopliteal atherosclerotic lesions. Methods: To evaluate the long-term clinical and angiographic outcome of EVBT, 147 consecutive patients (82 men; mean age 70.8±8.5 years) with 147 treated limbs were randomized to BA with (n=72, 49%) or without (n=75, 51%) adjunctive EVBT (12 or 14-Gy from an 192Ir source, no centering, a 5-mm reference depth). Sixty-eight (46%) limbs were treated for de novo and 79 (54%) for recurrent femoropopliteal lesions. Clinical follow-up at 1, 3, 6, and 12 months and annually thereafter included evaluation of symptoms, ankle-brachial index (ABI), and intra-arterial angiography for new/worsening symptoms or at follow-up between 2 and 5 years. Sustained clinical success was defined as improvement in ABI ≥0.1 and/or of symptoms without repeated target lesion revascularization. Angiographic restenosis was defined as ≥50% diameter reduction. Subgroup analysis was performed for de novo versus recurrent lesions. Results: Mean clinical follow-up was 32.3±21.5 months. Angiographic follow-up was available in 83 (56%) patients (41 BA and 42 BA+EVBT) at a mean 31.8±20.7 months. Cumulative sustained clinical success rates at 1, 2, and 3 years, respectively, were 84.3%, 82.1%, and 76.4% after BA versus 82.4%, 69.8%, and 67.5% after BA+EVBT (p=0.26 by log-rank). Although the proportion of patients undergoing follow-up angiography was moderate, the freedom from angiographic restenosis at 1, 2, and 3 years was 70.7%, 63.1%, and 47.1% after BA versus 82.7%, 64.3%, and 64.3% after BA+EVBT (p=0.16 by log-rank). No differences were found between BA and BA+EVBT outcomes in patients with de novo versus recurrent femoropopliteal lesions. Conclusion: The seemingly beneficial short-term effects of BA+EVBT are not sustained in the longer term, with no robust clinical improvement after angioplasty of atherosclerotic de novo or recurrent femoropopliteal lesions at up to 5 years.

Effects of probucol versus aspirin and versus brachytherapy on restenosis after femoropopliteal angioplasty: the PAB randomized multicenter trial.

Purpose: To evaluate the effect of probucol and/or of endovascular brachytherapy (EVBT) on restenosis after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries. Methods: A total of 335 patients (206 men; mean age 72±9 years) with intermittent claudication were randomized according to a 2×2 factorial design to 1 of the 4 groups: probucol, placebo, EVBT, and EVBT+probucol. Probucol (1 g/d) or placebo were given in double-blinded fashion 1 month before and for 6 months after PTA. Gamma irradiation (192Iridium, 14 Gy, 5-mm reference depth) was randomly applied in an unblinded manner from a noncentered endoluminal catheter. All patients received aspirin (100 mg/d). Primary endpoint was restenosis (>50% diameter reduction) detected by duplex ultrasound 6 months after PTA. Secondary endpoints included clinical and hemodynamic assessment. Results: Restenosis in patients undergoing EVBT was 17% (23/133) versus 35% (50/142) in patients without EVBT (p<0.001); in patients treated with probucol versus placebo, the rates were 23% (31/135) and 30% (43/140, p<0.001). Three quarters (77%, 102/133) of patients were free of claudication after EVBT therapy versus 61% (87/142) without EVBT (p<0.05). Need for target vessel revascularization was 6% (8/133) with EVBT versus 14% (20/142) without EVBT (p<0.01). Late thrombotic occlusions occurred in 4% (6/133), exclusively in patients treated with EVBT after stent implantation. Conclusions: Endovascular brachytherapy significantly reduces restenosis, improves symptoms, and reduces reinterventions after PTA of femoropopliteal arteries. Probucol reduces restenosis but has no additive effect when combined with brachytherapy.

Endovascular Brachytherapy after Percutaneous Transluminal Angioplasty of Recurrent Femoropopliteal Obstructions

Purpose: To test the preventive effect of endovascular brachytherapy (EVBT) on restenosis following secondary angioplasty in patients with presumed neointimal restenosis in the femoropopliteal segment. Methods: From March 1997 through May 2000, 100 patients (58 men; mean age 70 years, range 45–87) with postangioplasty femoropopliteal segment restenoses were enrolled and randomized to treatment with repeat angioplasty and EVBT (n = 51) or to angioplasty alone (n=49) as control. The groups were similar with regard to demographics and lesion characteristics. High-dose-rate EVBT was performed with 192Ir irradiation without a centering device (12 Gy for a reference vessel radius of 3 mm and a 2-mm reference depth). Primary endpoint in the 1-year follow-up was recurrent obstruction >50% documented by duplex ultrasound; the secondary endpoint was clinical improvement. Results: Only 44 (86%) of 51 patients received adequate EVBT due to technical failure, so the 7 failures were included with the controls in the per-protocol adherence analysis. At 1 year, the patients receiving EVBT had a restenosis rate of 23% (10/44), which differed significantly (p<0.028) from the 42% (23/56) rate in controls. Clinical results tended to be better with EVBT, but differences did not achieve statistical significance. Conclusions: EVBT without a centering device reduced restenosis significantly in patients with recurrent stenosis after angioplasty, which confirms previous results in primary long-segment femoropopliteal obstructions.

Influences of C3a anaphylatoxin compared to other vasoactive agents on the microcirculation of the rabbit omentum

Abstract The vasoactive effects of human C3a on arteriolar pressures and diameters of rabbit omenta were compared to the actions of norepinephrine, angiotensin II and histamine. Topical application of C3a reduced pressures in feeding or terminal arterioles (range 15–35 μm) to 56 ± 4% and diameters to 69 ± 4% of control values (both p i ) was not an effective constrictor but blocked the action of C3a and norepinephrine. Histamine produced a decrease in arteriolar pressure to 56 ± 7% ( p p i , suggest that the effect of C3a is related to the alpha-receptors and is independent of histamine release.