A.D. Pichard

Late thrombosis in drug-eluting coronary stents after discontinuation of antiplatelet therapy

Although the safety profiles of coronary stents eluting sirolimus or paclitaxel do not seem to differ from those of bare metal stents in the short-to-medium term, concern has arisen about the potential for late stent thromboses related to delayed endothelialisation of the stent struts. We report four cases of angiographically-confirmed stent thrombosis that occurred late after elective implantation of polymer-based paxlitaxel-eluting (343 and 442 days) or sirolimus-eluting (335 and 375 days) stents, and resulted in myocardial infarction. All cases arose soon after antiplatelet therapy was interrupted. If confirmed in systematic long-term follow-up studies, our findings have potentially serious clinical implications.

Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound

OBJECTIVESnThis study was designed to report the clinical and angiographic correlates of plaque rupture detected by intravascular ultrasound (IVUS).nnnBACKGROUNDnAcute coronary syndromes result from spontaneous plaque rupture and thrombosis.nnnMETHODSnWe report 300 plaque ruptures in 257 arteries in 254 patients. Plaque ruptures were detected during pre-intervention IVUS. Standard clinical, angiographic, and IVUS parameters were collected and/or measured. One lesion per patient was analyzed.nnnRESULTSnMultiple ruptures were observed in 39 of 254 patients (15%), 36 in the same artery. Plaque rupture occurred not only in patients with unstable angina (46%) or myocardial infarction (MI, 33%), but also stable angina (11%) or no symptoms (11%). The tear in the fibrous cap could be identified in 157 of 254 patients; 63% occurred at the shoulder of the plaque and 37% in the center of the plaque. Thrombi were more common in patients with unstable angina or MI (p = 0.02) and in multiple ruptures (p = 0.04). The plaque rupture site contained the minimum lumen area (MLA) site in only 28% of patients; rupture sites had larger arterial and lumen areas and more positive remodeling than MLA sites. Intravascular ultrasound plaque rupture strongly correlated with complex angiographic lesion morphology: ulceration in 81%, intimal flap in 40%, thrombus in 7%, and aneurysm in 7%.nnnCONCLUSIONSnPlaque ruptures occur with varying clinical presentations, strongly correlate with angiographic complex lesion morphology, may be multiple, and usually do not cause lumen compromise.

Vascular complications after balloon and new device angioplasty.

BackgroundDespite their potential advantages, new coronary angioplasty devices may be associated with more frequent vascular complications than noted after standard balloon angioplasty, theoretically due to the larger sheaths and prolonged periods of anticoagulation required by some of these devices. This study sought to identify the incidence, predictors, and clinical outcome of vascular complications after new device angioplasty. Methods and ResultsThe clinical course of 1413 patients was reviewed after balloon or new device angioplasty. Vascular complications were defined as formation of a pseudoaneurysm, arteriovenous fistula, retroperitoneal hematoma, or groin hematoma associated with a >15-point hematocrit drop or the need for surgical repair. Stepwise logistic regression was used to identify independent predictors for vascular complications. Vascular complications developed after 84 (5.9%o) procedures; they occurred more frequently after intracoronary stenting (14.0%o) and extraction atherectomy (12.5%) than after balloon angioplasty (3.2%) (odds ratios, 4.86; P<.001, and 4.26, p<.05, respectively). Independent predictors of vascular complications included the use of intraprocedural thrombolytic agents (P<.01), intracoronary stenting (P<.005), or extraction atherectomy (P<.05); high maximum creatinine level (P<.005); low nadir platelet count (P<.001); longer periods of excess anticoagulation (P<.05); and the need for repeat coronary angioplasty (P<.005). Vascular complications were not related to the size of the arterial sheath used. ConclusionsVascular complications developed more frequently after new device angioplasty than after balloon angioplasty, with the risk for vascular complications directly related to the degree of periprocedural anticoagulation.

Intravascular ultrasound evaluation of the effect of rotational atherectomy in obstructive atherosclerotic coronary artery disease.

BackgroundHigh-speed rotational atherectomy uses a diamxond-coated, elliptical burr to abrade occlusive atherosclerosis, especially noncompliant calcified plaque. Methods and ResultsIntravascular ultrasound (IVUS) was used to analyze 28 patients after atherectomy. Arteries treated and imaged were left main (three), left anterior descending (12), left circumflex (five), right coronary (seven), and saphenous vein graft (one). Twenty patients had adjunct balloon angioplasty. Twenty-two (79%) target lesions were calcified; the intimal arc of calcium was 160±126° (range, 0–360°). After atherectomy, the intima-lumen interface was unusually distinct and circular. The lumen was larger than the largest burr used for both stand-alone (1.19±0.19-fold the largest burr size) and adjunct balloon procedures (1.30±0.15-fold the largest burr). Three-dimensional reconstruction of the ultrasound images showed a smooth lumen, especially in calcified plaque. Deviations from cylindrical geometry occurred only in areas of soft plaque or superficial tissue disruption of calcified plaque. Five patients were studied before and after rotational atherectomy. IVUS showed an increase in lumen size, a decrease in plaque-plus-media area and in arc of target lesion calcification, and no change in target lesion external elastic membrane cross-sectional area. ConclusionsRotational atherectomy causes atheroablation with only moderate evidence ofbarotrauma in heavily calcified arteries, even after adjunct balloon angioplasty. The lumen is cylindrical, especially in areas of calcified plaque, and somewhat larger than the largest burr tip used.

Intravascular ultrasound assessment of spontaneous coronary artery dissection.

IVUS can diagnose spontaneous coronary dissections, especially those that are angiographically inapparent. IVUS features also include medial dissection with intramural hematoma, absence of an intimal tear, and minimal atherosclerosis.

Paradoxic Decreases in Atherosclerotic Plaque Mass in Insulin-Treated Diabetic Patients ☆

This study assessed the impact of diabetes mellitus on atherosclerotic lesion formation. Seventy insulin-treated diabetics, 150 non-insulin-treated diabetics, and 607 nondiabetics with chronic anginal syndromes and de novo native coronary stenoses were studied using (1) angiography, and (2) intravascular ultrasound (reference and lesion arterial, lumen, and plaque areas; area stenosis [reference-lesion/reference lumen area]; remodeling index [reference-lesion lumen area/lesion-reference plaque area]; and slope of the regression line relating lumen area to plaque burden [plaque/arterial area]). Despite being diabetic for longer and having similar lumen compromise, insulin-treated patients had (1) less reference plaque (8.3 +/- 3.4 vs 10.5 +/- 4.5 mm2, p = 0.0015), (2) less stenosis plaque (13.0 +/- 4.9 vs 16.9 mm2, p <0.0001), (3) smaller reference arterial areas (17.1 +/- 5.4 vs 19.7 +/- 6.2 mm2, p = 0.0063), and (4) smaller stenosis arterial areas (15.3 +/- 4.9 vs 19.5 +/- 6.5 mm2, p <0.0001) than non-insulin-treated diabetics. With use of multivariate linear regression analysis, insulin use was an independent (and negative) predictor of reference plaque and arterial areas (p = 0.0308 and p = 0.0179) and stenosis plaque and arterial areas (p = 0.0117 and p = 0.0066). This was also true when normalized for body surface area. The remodeling index showed that insulin treatment resulted in an exaggerated impact of plaque accumulation on lumen compromise. This was confirmed by the slope of the regression line relating lumen area to plaque burden. Patients with a longer duration of diabetes who were treated with insulin for > or = 1 year had (paradoxically) less reference segment and stenosis plaque accumulation. Possible explanations include impaired adaptive remodeling and/or arterial (and plaque) shrinkage.

An intravascular ultrasound classification of angiographic coronary artery aneurysms

The purpose of this study was to use intravascular ultrasound (IVUS) to clarify the morphology of coronary aneurysms diagnosed by angiography. Seventy-seven consecutive patients with an aneurysmal dilatation in a native coronary artery diagnosed by angiography (defined as a lesion lumen diameter 25% larger than reference) were evaluated by IVUS. IVUS true aneurysms were defined as having an intact vessel wall and a maximum lumen area 50% larger than proximal reference. IVUS pseudoaneurysms had a loss of vessel wall integrity and damage to adventitia or perivascular tissue. Complex plaques were lesions with ruptured plaque or spontaneous or unhealed dissection. Aneurysmal dilatation and reference segments were assessed using standard IVUS quantitative techniques. Twenty-one lesions (27%) were classified as true aneurysms, 3 (4%) were classified as pseudoaneurysms, 12 (16%) were complex plaques, and the other 41 (53%) were normal arterial segments adjacent to > or =1 stenosis. The maximum lumen area within the aneurysmal segment was largest for pseudoaneurysm (35.1 +/- 10.4 mm(2)), 22.1 +/- 9.9 mm(2) for true aneurysm, and similar for complex plaques (11.2 +/- 3.5 mm(2)) and normal segments with adjacent stenoses (13.8 +/- 6.4 mm(2)): analysis of variance, p <0.0001. Only one third of angiographically diagnosed aneurysms had the IVUS appearance of a true or pseudoaneurysm. Instead, most angiographically diagnosed aneurysms had the morphology of complex plaques or normal segments with adjacent stenoses.

Intravascular ultrasound assessment of the stenoses location and morphology in the left main coronary artery in relation to anatomic left main length.

Eighty-seven left main stenoses were evaluated by angiography and intravascular ultrasound. Intravascular ultrasound analysis included left main length (bifurcation to ostium), stenosis location, stenosis length, stenosis external elastic membrane, lumen, plaque & media cross-sectional area (CSA), plaque burden (plaque & media/external elastic membrane CSA), calcium arc, calcium length, eccentricity, and remodeling index (stenosis/reference external elastic membrane CSA). Long anatomic left main arteries (length > or =10 mm, n = 43) were compared with short anatomic left main arteries (length <10 mm, n = 44) regarding stenosis location. Ostial (proximal third of left main artery) (n = 32) and nonostial (midthird and distal third) stenoses (n = 55) were compared regarding stenosis morphology. Short anatomic left main arteries developed stenoses more frequently near the ostium (ostium 55%, bifurcation 38%). Conversely, long anatomic left main arteries developed stenoses more frequently near the bifurcation (ostium 18%, bifurcation 77%, p = 0.001). Ostial left main stenoses were more common in women (44% vs 20%, p = 0.02), had larger lumen area (6.2 +/- 2.2 vs 4.6 +/- 2.3 mm(2), p = 0.002), less plaque burden (62 +/- 15% vs 80 +/- 9%, p <0.0001), less calcification (arc = 78 +/- 65 degrees vs 195 +/- 101 degrees, p <0.0001), and more negative remodeling (remodeling index = 0.87 +/- 0.19 vs 1.01 +/- 0.21, p = 0.005) than nonostial left main stenoses. Most ostial left main stenoses were categorized as eccentric (97% vs 76%, p = 0.01). Short and long left main arteries develop stenoses at different locations. Stenosis morphology was significantly different in these 2 locations.

Mechanism of lumen enlargement with direct stenting versus predilatation stenting: influence of remodelling and plaque characteristics assessed by volumetric intracoronary ultrasound

Objective: To compare the effects of arterial remodelling and plaque characteristics on the mechanisms of direct stenting and predilatation stenting. Direct stenting has become routine in some laboratories and differs technically from predilatation stenting. Methods: Pre- and post-interventional volumetric intravascular ultrasound (IVUS) was undertaken in 30 patients with direct stenting and in 30 with predilatation stenting of non-calcified native coronary lesions, using the same stent design and stent length. Lumen, vessel (external elastic membrane (EEM)), and plaque (plaque + media) volumes were calculated. Remodelling was determined by comparing the EEM area at the centre of the lesion with the EEM areas at proximal and distal reference sites. Plaque eccentricity was defined as the thinnest plaque diameter to the thickest plaque diameter ratio. Plaque composition was characterised as soft, mixed, or dense. Results: All volumetric IVUS changes were similar in the two groups. Pre-intervention remodelling remained uninfluenced after direct stenting, but was neutralised after predilatation stenting. Eccentric lesions responded to intervention by a greater luminal gain owing to greater vessel expansion in direct stenting. Plaque composition influenced luminal gain in direct stenting, the gain being greatest in the softest plaques; in predilatation stenting, luminal gain was equivalent but vessel expansion was greater for “dense” plaque and plaque reduction greater for “soft” plaque. Conclusions: In non-calcified lesions, the mechanisms of lumen enlargement after direct or predilatation stenting are significantly influenced by atherosclerotic remodelling, plaque eccentricity, and plaque composition.

Emergence of the concept of platelet reactivity monitoring of response to thienopyridines

Clinical trials have demonstrated the beneficial impact of clopidogrel in preventing major adverse cardiovascular events (MACE), particularly in patients undergoing percutaneous coronary intervention (PCI). The concept of biological clopidogrel resistance emerged with the finding of persistent platelet activation despite clopidogrel therapy in some patients. Further, a link between biological clopidogrel resistance and thrombotic recurrence after PCI was observed and a threshold of platelet reactivity (PR) for thrombotic events was suggested. Consistently, in recent trials, enhanced PR inhibition translated into a reduction in the rate of MACE after PCI. This review aims to present the emergence of the concept of PR monitoring in patients undergoing PCI following recent advances in this field.