William O. Suddath

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.

Correlates and Long-Term Outcomes of Angiographically Proven Stent Thrombosis With Sirolimus- and Paclitaxel-Eluting Stents

Background— Stent thrombosis (ST) is a serious complication of drug-eluting stent (DES) implantation regardless of the timing (acute, subacute, or late). The correlates of ST with DES are not yet completely elucidated. Methods and Results— From a total cohort of 2974 consecutive patients treated with DES since April 2003, we identified 38 patients who presented with angiographic evidence of ST (1.27%). The ST occurred acutely in 5 patients, subacutely (≤30 days) in 25 patients, and late (>30 days) in 8 patients. The clinical, angiographic, and procedural variables of these patients were compared with the remaining 2936 consecutive patients who underwent DES implantation and did not experience ST during a follow-up of 12 months. Logistic regression analysis was conducted to determine the correlates of ST. Compared with patients without ST, patients with ST had a higher frequency of diabetes, acute postprocedural renal failure, and chronic renal failure. There were more bifurcation lesions, type C lesions, and a trend for smaller-diameter stents. Discontinuation of clopidogrel was higher in these patients (36.8% versus 10.7%; P<0.0001). The mean duration to ST from the stent implantation was 8.9±8.5 days in subacute and 152.7±100.4 days in late thrombosis cases. Mortality was significantly higher in patients with ST compared with those without ST at 6 months (31% versus 3%; P<0.001). Multivariate analysis detected cessation of clopidogrel therapy, renal failure, bifurcation lesions, and in-stent restenosis as significant correlates of ST (P<0.05). Conclusions— ST continues to be a serious complication of contemporary DES use. Careful management is warranted in patients with renal failure and in those undergoing treatment for in-stent restenosis and bifurcations. Special focus on clopidogrel compliance may minimize the incidence of ST after DES implantation.

The impact of obesity on the short-term andlong-term outcomes after percutaneous coronary intervention: the obesity paradox?

OBJECTIVES The purpose of this study was to assess the impact of body mass index (BMI) on the short- and long-term outcomes after percutaneous coronary intervention (PCI). BACKGROUND Obesity is associated with advanced coronary artery disease (CAD). However, the relation between BMI and outcome after PCI remains controversial. METHODS We studied 9,633 consecutive patients who underwent PCI between January 1994 and December 1999. Patients were divided into three groups according to BMI: normal, BMI between 18.5 and 24.9 (n = 1,923); overweight, BMI between 25 and 30 (n = 4,813); and obese, BMI >30 (n = 2,897). RESULTS Obese patients were significantly younger and had consistently worse baseline clinical characteristics than normal or overweight patients, with a higher incidence of hypertension, diabetes, hypercholesterolemia and smoking history (p < 0.0001). Despite similar angiographic success rates among the three groups, normal BMI patients had a higher incidence of major in-hospital complications, including cardiac death (p = 0.001). At one-year follow-up, overall mortality rates were significantly higher for normal BMI patients compared with overweight or obese patients (p < 0.0001). Myocardial infarction and revascularization rates did not differ among the three groups. By multivariate Cox regression analysis, diabetes, hypertension, age, BMI and left ventricular function were independent predictors of long-term mortality. CONCLUSIONS In patients with known CAD who undergo PCI, very lean patients (BMI <18.5) and those with BMI within the normal range are at the highest risk for in-hospital complications and cardiac death and for increased one-year mortality.

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

OBJECTIVES This study was designed to report the clinical and angiographic correlates of plaque rupture detected by intravascular ultrasound (IVUS). BACKGROUND Acute coronary syndromes result from spontaneous plaque rupture and thrombosis. METHODS We 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. RESULTS Multiple 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%. CONCLUSIONS Plaque ruptures occur with varying clinical presentations, strongly correlate with angiographic complex lesion morphology, may be multiple, and usually do not cause lumen compromise.

The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents

AIMS To assess the impact on clinical outcomes of intravascular ultrasound (IVUS) guidance during drug-eluting stent (DES) implantation. IVUS guidance during percutaneous coronary intervention (PCI) has been demonstrated to be useful in optimizing stent deployment. However, it is not proved that routine use of IVUS guidance with DES implantation can prevent stent thrombosis or restenosis. METHODS AND RESULTS The clinical outcomes of 884 patients undergoing IVUS-guided intracoronary DES implantation from April 2003 to May 2006 were compared with the outcomes of a propensity-score matched population undergoing DES implantation with angiographic guidance alone. The primary endpoint of the study was definite stent thrombosis at 12 months. The secondary endpoint was major adverse cardiac events (MACE). After propensity-score matching, the two groups were well matched for clinical and angiographic characteristics. Patients undergoing IVUS-guided DES implantation underwent less direct stenting, more post-dilation, and had greater cutting balloon and rotational atherectomy use. At 30 days and at 12 months, a higher rate of definite stent thrombosis was seen in the No IVUS group (0.5 vs. 1.4%; P = 0.046) and (0.7 vs. 2.0%; P = 0.014), respectively. There were no major differences in late stent thrombosis and MACE (14.5 vs. 16.2%; P = 0.33) at 12 month follow-up between the groups. Rates of death and Q-wave myocardial infarction were similar, and there was no significant difference between groups in target vessel revascularization. However, a trend was seen in favour of the IVUS group in target lesion revascularization (5.1 vs. 7.2%; P = 0.07). IVUS guidance was an independent predictor of freedom from cumulative stent thrombosis at 12 months (adjusted HR 0.5, CI 0.1-0.8; P = 0.02). CONCLUSION IVUS guidance during DES implantation has the potential to influence treatment strategy and reduce both DES thrombosis and the need for repeat revascularization.

Intravascular Ultrasound Analysis of Infarct-Related and Non–Infarct-Related Arteries in Patients Who Presented With an Acute Myocardial Infarction

Background Previous studies have reported diffuse destabilization of atherosclerotic plaques in acute myocardial infarction (AMI). Methods and Results We used intravascular ultrasound (IVUS) to assess 78 coronary arteries (38 infarct‐related arteries [IRAs] with culprit and nonculprit lesions and 40 non‐IRAs) from 38 consecutive AMI patients. IVUS analysis included qualitative and quantitative measurements of reference and lesion external elastic membrane (EEM), lumen, and plaque plus media (P&M) area. Positive remodeling was defined as lesion/mean reference EEM>1.0. Culprit lesions were identified by a combination of ECG, wall motion abnormalities (ventriculogram or echocardiogram), scintigraphic perfusion defects, and coronary angiogram. Culprit lesions contained more thrombus (23.7% versus 3.4% in nonculprit IRA plaques and 3.1% in non‐IRA plaques; P<0.0011). Culprit lesions were predominantly hypoechoic (63.2% versus 37.9% of nonculprit IRA plaques and 28.1% of non‐IRA plaques; P=0.0022). Culprit lesions were longer (17.5±10.1, 9.8±4.0, and 10.3±5.7 mm, respectively; P<0.0001), had larger EEM area (15.0±6.0, 11.5±5.7, and 12.6±5.6 mm2, respectively; P±0.0353) and P&M area (13.0±6.0, 7.5±3.7, 9.3±4.3 mm2, respectively; P<0.0001), smaller lumens (2.0±0.9,4.1±3.1, and 3.4±2.5mm2, respectively; P=0.0009), and more positive remodeling (79.4%, 59.0%, and 50.8%, respectively; P=0.0155). The frequency of plaque rupture/dissection was greater in culprit, nonculprit IRA, and non‐IRA plaques in AMI patients than in a control group of chronic stable angina patients with multivessel IVUS imaging. Conclusions Culprit plaques have more markers of instability (thrombus, positive remodeling, and large plaque mass); however, these markers of instability are not typically found elsewhere. This suggests that the vascular event in AMI patients is determined by local pre‐event lesion morphologies. (Circulation. 2003;107:2889‐2893.)

A First-in-Man, Randomized, Placebo-Controlled Study to Evaluate the Safety and Feasibility of Autologous Delipidated High-Density Lipoprotein Plasma Infusions in Patients With Acute Coronary Syndrome

OBJECTIVES This study aimed to determine whether serial autologous infusions of selective high-density lipoprotein (HDL) delipidated plasma are feasible and well tolerated in patients with acute coronary syndrome (ACS). BACKGROUND Low HDL is associated with increased risk of cardiovascular disease. Plasma selective delipidation converts alphaHDL to prebeta-like HDL, the most effective form of HDL for lipid removal from arterial plaques. METHODS ACS patients undergoing cardiac catheterization with >or=1 nonobstructive native coronary artery atheroma were randomized to either 7 weekly HDL selective delipidated or control plasma apheresis/reinfusions. Patients underwent intravascular ultrasound (IVUS) evaluation of the target vessel during the catheterization for ACS and up to 14 days following the final apheresis/reinfusion session. 2-D gel electrophoresis of delipidated plasmas established successful conversion of alphaHDL to prebeta-like HDL. The trial was complete with 28 patients randomized. RESULTS All reinfusion sessions were tolerated well by all patients. The levels of prebeta-like HDL and alphaHDL in the delipidated plasma converted from 5.6% to 79.1% and 92.8% to 20.9%, respectively. The IVUS data demonstrated a numeric trend toward regression in the total atheroma volume of -12.18 +/- 36.75 mm(3) in the delipidated group versus an increase of total atheroma volume of 2.80 +/- 21.25 mm(3) in the control group (p = 0.268). CONCLUSIONS In ACS patients, serial autologous infusions of selective HDL delipidated plasma are clinically feasible and well tolerated. This therapy may offer a novel adjunct treatment for patients presenting with ACS. Further study will be needed to determine its ability to reduce clinical cardiovascular events.

Stroke Complicating Percutaneous Coronary Interventions Incidence, Predictors, and Prognostic Implications

Background—Stroke associated with percutaneous coronary intervention (PCI) is an infrequent although devastating complication. We investigated the incidence, predictors, and prognostic impact of periprocedural stroke in unselected patients undergoing PCI. Methods and Results—A total of 9662 patients who underwent 12 407 PCIs between January 1990 and July 1999 were retrospectively studied. Stroke was diagnosed in 43 patients (0.38% of procedures). Patients with stroke were older (72±11 versus 64±11 years, P <0.001), had lower left ventricular ejection fraction (42±12 versus 46±13%, P =0.04) and more diabetes (39.5% versus 27.2%, P =0.07), and experienced a higher rate of intraprocedural complications necessitating emergency use of intra-aortic balloon pump (IABP) (23.3% versus 3.3%, P <0.001). In-hospital mortality (37.2% versus 1.1%, P <0.001) and 1-year mortality (56.1% versus 6.5%, P <0.001) were higher in patients with stroke. Compared with hemorrhagic stroke, patients with ischemic stroke had higher rate of in-hospital major adverse cardiac events (57.1% versus 25%, P =0.037). Multivariate logistic regression analysis identified emergency use of IABP as the strongest predictors for stroke (OR=9.6, CI 3.9 to 23.9, P <0.001), followed by prophylactic use of IABP (OR=5.1), age >80 years (OR=3.2, compared with age <50 years), and vein graft intervention (OR=2.7). Conclusions—Stroke associated with contemporary PCI is associated with substantial increased mortality. Elderly patients who experience intraprocedural complications necessitating the use of IABP are at particularly high risk.

Outcomes of Coronary Artery Bypass Grafting Versus Percutaneous Coronary Intervention With Drug-Eluting Stents for Patients With Multivessel Coronary Artery Disease

Background— Advances in coronary artery bypass grafting (CABG) surgery and percutaneous coronary intervention (PCI) with drug-eluting stents have dramatically improved results of these procedures. The optimal treatment for patients with multivessel coronary artery disease is uncertain given the lack of prospective, randomized data reflecting current practice. This study represents a “real-world” evaluation of current technology in the treatment of multivessel coronary artery disease. Methods and Results— A total of 1680 patients undergoing revascularization for multivessel coronary artery disease were identified. Of these, 1080 patients were treated for 2-vessel disease (196 CABG and 884 PCI) and 600 for 3-vessel disease (505 CABG and 95 PCI). One-year mortality, cerebrovascular events, Q-wave myocardial infarction, target vessel failure, and composite major adverse cardiovascular and cerebrovascular events were compared between the CABG and PCI cohorts. Outcomes were adjusted for baseline covariates and reported as hazard ratios. The unadjusted major adverse cardiovascular and cerebrovascular event rate was reduced with CABG for patients with 2-vessel disease (9.7% CABG versus 21.2% PCI; P<0.001) and 3-vessel disease (10.8% CABG versus 28.4% PCI; P<0.001). Adjusted outcomes showed increased major adverse cardiovascular and cerebrovascular event with PCI for patients with 2-vessel (hazard ratio 2.29; 95% CI 1.39 to 3.76; P=0.01) and 3-vessel disease (hazard ratio 2.90; 95% CI 1.76 to 4.78; P<0.001). Adjusted outcomes for the nondiabetic subpopulation demonstrated equivalent major adverse cardiovascular and cerebrovascular event with PCI for 2-vessel (hazard ratio 1.77; 95% CI 0.96 to 3.25; P=0.07) and 3-vessel disease (hazard ratio 1.70; 95% CI 0.77 to 3.61; P=0.19). Conclusions— Compared with PCI with drug-eluting stents, CABG resulted in improved major adverse cardiovascular and cerebrovascular event in patients with 2- and 3-vessel coronary artery disease, primarily in those with underlying diabetes. Coronary artery bypass surgery may be the preferred revascularization strategy in diabetic patients with multivessel coronary artery disease.

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.