Adverse Cardiovascular Events Arising From Atherosclerotic Lesions With and Without Angiographic Disease Progression

ObjectivesThe aim of this study was to use angiography and grayscale and intravascular ultrasound–virtual histology to assess coronary lesions that caused events during a median follow-up period of 3.4 years.BackgroundVulnerable plaque-related events are assumed to be the result of substantial progression of insignificant lesions.MethodsIn the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with acute coronary syndromes underwent treatment of all culprit lesions followed by 3-vessel imaging to assess the natural history of culprit and untreated nonculprit (NC) lesions. Future adverse cardiovascular events adjudicated to NC lesions were divided into those with versus without substantial lesion progression (SLP) (≥20% angiographic diameter stenosis increase).ResultsNC lesion events occurred in 72 patients, 44 (61%) with and 28 (39%) without SLP. Myocardial infarctions (n = 6) occurred only in patients with SLP. Conversely, patients without SLP presented only with unstable or increasing angina requiring rehospitalization. Lesions with versus without SLP occurred later (median time to event 401 vs. 223 days, p = 0.07); were less severe at baseline (median diameter stenosis 26.4% vs. 53.8%, p < 0.0001) but more severe at the time of the event (mean diameter stenosis 73.8% vs. 56%, p < 0.0001); and had comparable baseline median plaque burden (68.7% vs. 70.1%, p = 0.17), minimum luminal area (3.7 vs. 4.0 mm2, p = 0.60), and intravascular ultrasound–virtual histology phenotype (83.3% vs. 90.9%, p = 0.68; classified as fibroatheromas at baseline).ConclusionsNC lesions responsible for future cardiovascular events showed angiographic increase during 3.4 years of follow-up, whereas SLP underlay many but not all of them. NC events due to lesions with SLP were angiographically less severe and presented with a delayed time course but were otherwise indistinguishable from NC events that were not associated with SLP

Effect of everolimus introduction on cardiac allograft vasculopathy--results of a randomized, multicenter trial.

BACKGROUND Everolimus reduces the progression of cardiac allograft vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown. METHODS In this Nordic Certican Trial in Heart and lung Transplantation substudy, 111 maintenance HTx recipients (time post-HTx 5.8 ± 4.3 years) randomized to everolimus+reduced calcineurin inhibitor (CNI) or standard CNI had matching (intravascular ultrasound) examinations at baseline and 12 months allowing accurate assessment of CAV progression. RESULTS No significant difference in CAV progression was evident between the treatment groups (P = 0.30). When considering patients receiving concomitant azathioprine (AZA) therapy (n = 39), CAV progression was attenuated with everolimus versus standard CNI (Δmaximal intimal thickness 0.00 ± 0.04 and 0.04 ± 0.04 mm, Δpercent atheroma volume 0.2% ± 3.0% and 2.6% ± 2.5%, and Δtotal atheroma volume 0.25 ± 14.1 and 19.8 ± 20.4 mm(3), respectively [P < 0.05]). When considering patients receiving mycophenolate mofetil (MMF), accelerated CAV progression occurred with everolimus versus standard CNI (Δmaximal intimal thickness 0.06 ± 0.12 vs. 0.02 ± 0.06 mm and Δpercent atheroma volume 4.0% ± 6.3% vs. 1.4% ± 3.1%, respectively; P < 0.05). The levels of C-reactive protein and vascular cell adhesion molecule-1 declined significantly with AZA+everolimus, whereas MMF+everolimus patients demonstrated a significant increase in levels of C-reactive protein, vascular cell adhesion molecule-1, and von Willebrand factor. CONCLUSIONS Conversion to everolimus and reduced CNI does not influence CAV progression among maintenance HTx recipients. However, background immunosuppressive therapy is important as AZA+everolimus patients demonstrated attenuated CAV progression and a decline in inflammatory markers, whereas the opposite pattern was seen with everolimus+MMF. The different effect of everolimus when combined with AZA versus MMF could potentially reflect hitherto unknown interactions

Coronary Plaque Composition, Morphology, and Outcomes in Patients With and Without Chronic Kidney Disease Presenting With Acute Coronary Syndromes

ObjectivesThis study sought to evaluate the impact of chronic kidney disease (CKD) on coronary atherosclerotic plaque composition, morphology, and outcomes in patients with acute coronary syndromes (ACS).BackgroundCKD patients presenting with ACS are at increased risk for adverse events. Whether or not this increased risk reflects differences in coronary plaque composition remains unknown.MethodsIn the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with ACS in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and radiofrequency intravascular ultrasound imaging. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. We conducted a patient-level and lesion-level analysis of study participants by comparing intravascular ultrasound parameters of untreated nonculprit lesions in patients with and without CKD.ResultsPatients with CKD (n = 73, 11.3%) were older, more often female and diabetic compared to those without CKD (n = 573). Nonculprit lesions in patients with (n = 280) versus without (n = 2,390) CKD were more likely to have plaque burden ≥70% (11.8% vs. 8.5%, p = 0.05) and minimal luminal area ≤4.0 mm2 (25.9% vs. 19.2%, p = 0.005). The percentage of plaque comprised of necrotic core (15.0% vs. 13.0%, p = 0.0001) and dense calcium (8.2% vs. 6.4%, p < 0.0001) was higher while fibrous tissue (57.7% vs. 59.8%, p < 0.0001) was lower in CKD versus non-CKD lesions. The 3-year composite rate of cardiac death, cardiac arrest, or myocardial infarction (15.1% vs. 3.3%, p < 0.0001) was significantly higher in patients with than in those without CKD, although there were no differences in the rates of events adjudicated to nonculprit lesions.ConclusionsFollowing percutaneous coronary intervention of all culprit lesions in ACS, patients with versus without CKD have more extensive and severe atherosclerosis remaining in their coronary tree with plaque composed of greater necrotic core and less fibrous tissue. These influences resulted in nonsignificantly different rates of non-culprit lesion–related adverse events, although cardiac death, arrest, or myocardial infarction were more common in patients with CKD