[Show abstract][Hide abstract] ABSTRACT: Purpose: Atherosclerotic plaques progress in a highly individual manner. Plaque eccentricity has been associated with a rupture-prone phenotype and adverse coronary events in humans. Endothelial shear stress (ESS) critically determines plaque growth and low ESS leads to high-risk lesions. However, the factors responsible for rapid disease progression with increasing plaque eccentricity have not been studied. We investigated in vivo the effect of local hemodynamic and plaque characteristics on progressive luminal narrowing with increasing plaque eccentricity in humans.
Methods: Three-dimensional coronary artery reconstruction using angiographic and intravascular ultrasound data was performed in 374 patients at baseline (BL) and 6-10 months later (FU) to assess plaque natural history as part of the PREDICTION Trial. A total of 874 coronary arteries were divided into consecutive 3-mm segments. We identified 408 BL discrete luminal narrowings with a throat in the middle surrounded by gradual narrowing proximal and distal to the throat. Local BL ESS was assessed by computational fluid dynamics. The eccentricity index (EI) at BL and FU was computed as the ratio of max to min plaque thickness at the throat. Mixed-effects logistic regression was used to investigate the effect of BL variables on the combined endpoint of substantial worsening of luminal narrowing (decrease in lumen area >1.8 mm2 or >20%) with an increase in plaque EI.
Results: Lumen worsening with an increase in plaque EI was evident in 73 luminal narrowings (18%). Independent predictors of worsening lumen narrowing with plaque EI increase were low BL ESS (<1 Pa) distal to the throat (odds ratio [OR] =2.2 [95% CI: 1.3-3.7]; p=0.003) and large BL plaque burden (>51%) at the throat (OR=1.7 [95% CI: 1.0-2.8]; p=0.051). The incidence of worsening lumen narrowing with increasing plaque eccentricity was 30% in the presence of both predictors versus 15% in luminal narrowings without this combination of characteristics (OR=2.4 [95% CI: 1.4-4.3]; p=0.002).
Conclusions: Low local ESS independently predicts areas with rapidly progressive luminal narrowing and increasing plaque eccentricity. Coronary regions manifesting an abrupt anatomic change, i.e., at highest risk to cause an adverse event, can be identified early by assessment of ESS and plaque burden.
[Show abstract][Hide abstract] ABSTRACT: The time course of atherosclerosis burden in distinct vascular territories remains poorly understood. We longitudinally evaluated the natural history of atherosclerotic progression in two different arterial territories using high spatial resolution magnetic resonance imaging (HR-MRI), a powerful, safe, and non-invasive tool.
We prospectively studied a cohort of 30 patients (mean age 68.3, n = 9 females) with high Framingham general cardiovascular disease 10-year risk score (29.5%) and standard medical therapy with mild-to-moderate atherosclerosis intra-individually at the level of both carotid and femoral arteries. A total of 178 HR-MRI studies of carotid and femoral arteries performed at baseline and at 1- and 2-year follow-up were evaluated in consensus reading by two experienced readers for lumen area (LA), total vessel area (TVA), vessel wall area (VWA = TVA - LA), and normalized wall area index (NWI = VWA/TVA). At the carotid level, LA decreased (-3.19%/year, P = 0.018), VWA increased (+3.83%/year, P = 0.019), and TVA remained unchanged. At the femoral level, LA remained unchanged, VWA and TVA increased (+5.23%/year and +3.11%/year, both P < 0.01), and NWI increased for both carotid and femoral arteries (+2.28%/year, P = 0.01, and +1.8%/year, P = 0.033).
The atherosclerotic burden increased significantly in both carotid and femoral arteries. However, carotid plaque progression was associated with negative remodelling, whereas the increase in femoral plaque burden was compensated by positive remodelling. This finding could be related to anatomic and flow differences and/or to the distinct degree of obstruction in the two arterial territories.
European Heart Journal 09/2011; 33(2):230-7. DOI:10.1093/eurheartj/ehr332 · 15.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to assess in vivo the long-term effects of percutaneous transluminal angioplasty (PTA) and endovascular brachytherapy (EVBT) on vessel wall by serial MRI.
Twenty patients with symptomatic stenosis of the femoropopliteal artery were randomly assigned to PTA (n=10) or PTA+EVBT (n=10, 14Gy by gamma-source). High-resolution MRI was performed prior, at 24-hours, 3-months, and 24-months after intervention. MRI data were analyzed by an independent, blinded observer.
The effects of both procedures on vessel wall at 24-hours and 3-months have been reported. Despite similar percent decrease in lumen area between 3- and 24-months in both groups (-8% for PTA and -11% for PTA+EVBT), at 24-months lumen area gain compared to baseline was +30% in PTA versus +82% in PTA+EVBT (p<0.05). Total vessel area, which was increased at 24-hours and 3-months, returned to pre-treatment value in both groups.
We demonstrated non-invasively that restenosis and inward remodeling after PTA are delayed by EVBT. At 24-months, patients treated with brachytherapy have larger lumen than those treated with PTA alone. The decrease in luminal and total vessel area between 3- and 24-months after EVBT indicates that the restenotic and remodeling process is not abolished but delayed with this therapy.
European Journal of Vascular and Endovascular Surgery 11/2007; 34(4):416-23. DOI:10.1016/j.ejvs.2007.05.017 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the effect of probucol and/or of endovascular brachytherapy (EVBT) on restenosis after percutaneous transluminal angioplasty (PTA) of femoropopliteal arteries.
A total of 335 patients (206 men; mean age 72+/-9 years) with intermittent claudication were randomized according to a 2x2 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.
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.
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.