Two-year outcome after treatment of severely calcified lesions with newer-generation drug-eluting stents in acute coronary syndromes: A patient-level pooled analysis from TWENTE and DUTCH PEERS.

BACKGROUND: Data on medium-term outcome of patients with acute coronary syndrome (ACS), treated with newer-generation durable polymer drug-eluting stents (DES) in severely calcified coronary lesions, are scarce. We aimed to assess the impact of severe coronary lesion calcification on clinical outcome of patients with ACS, treated with newer-generation DES. METHODS: The TWENTE and DUTCH PEERS randomized trials comprise 1779 ACS patients, who were categorized into patients with versus without severe target lesion calcification. We performed a patient-level pooled analysis to assess 2-year outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS: Patients with severe target lesion calcification (n=340, 19.1%) were older (66.8±10.6 years vs. 62.8±11.5 years, p<0.001) and had more often diabetes (22.1% vs. 16.8%, p=0.02) and hypercholesterolemia (51.5% vs. 42.9%, p=0.005) than other patients (n=1439, 79.9%). In addition they showed a higher TVF rate (12.4% vs.7.0%, p=0.001), mainly related to a difference in TVR (6.8% vs. 3.3%, p=0.003). There was a borderline significant between-group difference in cardiac death (3.6% vs. 1.8%, p=0.05), but not in target vessel MI (3.8% vs.2.6%, p=0.23) and definite stent thrombosis (0.9% vs. 0.6%, p=0.71). Multivariate analysis demonstrated that severe lesion calcification was an independent risk factor of TVF (adjusted HR; 1.58, 95% CI: 1.23-2.03; p<0.001). CONCLUSIONS: In patients with ACS, treatment of severely calcified lesions with newer-generation DES was associated with an overall higher clinical event risk - related in particular to a higher TVR rate, while the risk of MI was low.

Impact of severe lesion calcification on clinical outcome of patients with stable angina, treated with newer generation permanent polymer-coated drug-eluting stents: A patient-level pooled analysis from TWENTE and DUTCH PEERS (TWENTE II).

BACKGROUND: The outcome of percutaneous coronary intervention with newer generation permanent polymer-coated drug-eluting stents (DES) in patients with severely calcified lesions is greatly unknown. We assessed the impact of severe lesion calcification on clinical outcome in patients with stable angina who underwent percutaneous coronary intervention with newer generation DES. METHODS: TWENTE and DUTCH PEERS randomized trials enrolled 1423 patients with stable angina, who were categorized into patients with versus without severe target lesion calcification. A patient-level pooled analysis assessed clinical outcome, including target vessel failure (TVF), a composite of cardiac death, target vessel-related myocardial infarction, or target vessel revascularization (TVR). RESULTS: Patients with severe calcification (n = 342) were older (66.6 ± 9.1 vs 64.2 ± 9.8 years, P < .001) and had more diabetes (25.7% vs 20.4%, P = .04) than other patients (n = 1081). Patients with calcified lesions had higher rates of TVF (16.4% vs 9.8%, pLogrank = .001), cardiac death (4.4% vs 1.5%, P = .03), target vessel myocardial infarction (7.6% vs 3.4%, P = .001), and definite stent thrombosis (1.8% vs 0.4%, P = .02). Multivariate analysis demonstrated that severe calcification was an independent risk factor of 2-year TVF (HR 1.42, 95% CI: 1.02-1.99, pLogrank = .04); landmark analysis showed that this was based on a difference during the first year (periprocedural: 5.8% vs. 3.1%, pLogrank = .02; first year: 7.5% vs. 3.8%, pLogrank = .007; second year: 4.1% vs. 3.3%, pLogrank = .54). CONCLUSION: In patients with stable angina, severe target lesion calcification is associated with an increased risk of adverse cardiovascular events following treatment with newer generation permanent polymer-coated DES. This increase in risk is restricted to the first year of follow-up, which is an encouraging finding.

Multicenter assessment of the reproducibility of volumetric radiofrequency-based intravascular ultrasound measurements in coronary lesions that were consecutively stented.

To assess in a multicenter design the between-center reproducibility of volumetric virtual histology intravascular ultrasound (VH-IVUS) measurements with a semi-automated, computer-assisted contour detection system in coronary lesions that were consecutively stented. To evaluate the reproducibility of volumetric VH-IVUS measurements, experienced analysts of 4 European IVUS centers performed independent analyses (in total 8,052 cross-sectional analyses) to obtain volumetric data of 40 coronary segments (length 20.0 ± 0.3 mm) from target lesions prior to percutaneous intervention that were performed in the setting of stable (65%) or unstable angina pectoris (35%). Geometric and compositional VH-IVUS measurements were highly correlated for the different comparisons. Overall intraclass correlation for vessel, lumen, plaque volume and plaque burden was 0.99, 0.92, 0.96, and 0.83, respectively; for fibrous, fibro-lipidic, necrotic core and calcified volumes overall intraclass correlation was 0.96, 0.94, 0.98, and 0.99, respectively. Nevertheless, significant differences for both geometrical and compositional measurements were seen. Of the plaque components, fibrous tissue and necrotic core showed on average the highest measurement reproducibility. A central analysis for VH-IVUS multicenter studies of lesions prior to PCI should be pursued. Moreover, it may be problematical to pool VH-IVUS data of individual trials analyzed by independent centers.

Incidence of periprocedural myocardial infarction following stent implantation: comparison between first- and second-generation drug-eluting stents.

BACKGROUND: First- and second-generation drug-eluting stents (DES) differ in coating materials, which may influence the incidence of periprocedural myocardial infarction (PMI). OBJECTIVE: To compare the incidence of PMI between first- and second-generation DES, using the current Academic Research Consortium (ARC) definition of PMI. METHODS: We assessed 800 patients treated with first- (Taxus Liberté or Endeavor) or second-generation DES (Xience V or Resolute). Each DES group consisted of 200 consecutive patients, who were treated during the transition from first- to second-generation DES. Routine peri-interventional assessment of cardiac biomarkers was performed to compare the incidence of PMI between DES groups according to the updated definition by the ARC: 2x upper reference limit of creatine kinase (CK), confirmed by CK-MB elevation. RESULTS: In 800 patients, a total of 1,522 DES (363 Taxus; 385 Endeavor; 382 Xience V; 392 Resolute) were implanted to treat 1,232 lesions. Patient characteristics did not differ between groups. In patients receiving second-generation DES, more multivessel percutaneous coronary interventions were performed (P = 0.01). The overall incidence of PMI was 4.75%. Between first- and second-generation DES, there was no significant difference in PMI (5.5% vs. 4.0%; P = 0.29). In a multivariate analysis, only the total number of stents implanted (P < 0.001) and presentation with acute coronary syndrome (P = 0.02) were independent predictors of PMI. CONCLUSION: Using the revised ARC definition, we found no significant difference in PMI between first- and second-generation DES. Overall, PMI occurred in 4.75%, which is 58% lower than with use of the historical PMI definition.

Impact of analyzing fewer image frames per segment during offline volumetric radiofrequency-based intravascular ultrasound measurements of target lesions prior to percutaneous coronary interventions.

In the present study, we evaluated the impact of a 50% reduction in number of image frames (every second frame) on the analysis time and variability of offline volumetric radiofrequency-based intravascular ultrasound (RF-IVUS) measurements in target lesions prior to percutaneous coronary interventions (PCI). Volumetric RF-IVUS data of vessel geometry and plaque composition are generally obtained by a semi-automated analysis process that includes time-consuming manual contour editing. A reduction in the number of frames used for volumetric analysis may speed up the analysis, but could increase measurement variability. We repeatedly performed offline volumetric analyses in RF-IVUS image sets of 20 mm-long coronary segments that contained 30 de novo lesions prior to PCI. A 50% reduction in frames decreased the analysis time significantly (from 57.5 ± 7.3 to 35.7 ± 3.7 min; P < 0.0001) while geometric and compositional RF-IVUS measurements did not differ significantly from measurements obtained from all frames. The variability between measurements on the reduced number of frames versus all frames was comparable to the intra-observer measurement variability. In target lesions prior to PCI, offline volumetric RF-IVUS analyses can be performed using a reduced number of image frames (every second frame). This reduces the time of analysis without substantially increasing measurement variability.

Serial intravascular ultrasound assessment of changes in coronary atherosclerotic plaque dimensions and composition: an update.

This manuscript reviews the use of serial intravascular ultrasound (IVUS) examination of coronary atherosclerosis in recent observational studies and randomized trials that revealed the effects of cholesterol-lowering and lipid-modifying therapies and offered novel insight into plaque progression and regression. We discuss the value of plaque progression-regression as complementary imaging endpoint and potential surrogate marker of cardiovascular event risk. In addition, the progress in serial assessment of coronary plaque composition and plaque vulnerability by radiofrequency-based analyses is reviewed. Finally, we report on the evaluation of true vessel remodelling in recent serial IVUS trials and discuss the future perspective of serial invasive imaging of coronary atherosclerosis.

Ultrasound and light: friend or foe? On the role of intravascular ultrasound in the era of optical coherence tomography.

More than 20 years after its introduction, intravascular ultrasound (IVUS) has outlived many other intracoronary techniques. IVUS was useful to solve many interventional problems and assisted us in understanding the dynamics of atherosclerosis. It serves as an established imaging endpoint in large progression-regression trial and as an important workhorse in many catheterization laboratories. Nowadays, increasingly complex lesions are treated with drug-eluting stents. The application of IVUS during such interventions can be very useful. Recently, optical coherence tomography (OCT), a light-based imaging technique, has entered the clinical arena. The "omnipresence" of OCT during scientific sessions and live courses with PCI may raise in many the question: Does IVUS have a future in the "era of OCT"? Three review articles, highlighted by this editorial, demonstrate the broad spectrum of current IVUS applications and underline the significant role of IVUS during the last two decades. OCT, the much younger technique, still has to prove its value. Yet OCT is likely to take over some of the current indications of IVUS as a research tool. In addition, OCT is currently gaining clinical significance for stent optimization during complex interventional procedures. Nevertheless, there is little doubt that IVUS still has a major role in studies on coronary atherosclerosis and for guidance of coronary stenting. Thus, ultrasound and light--are they friend or foe? In fact, both methods are good in their own rights. They are complementary rather than competitive. Moreover, in combination, at least for certain indications, they could be even better.

Between-centre reproducibility of volumetric intravascular ultrasound radiofrequency-based analyses in mild-to-moderate coronary atherosclerosis: an international multicentre study.

AIMS: To assess for the first time in a multicentre design the between-centre reproducibility of volumetric virtual histology intravascular ultrasound (VH-IVUS) measurements with a semi-automated, computerassisted contour detection system in mild-to-moderately diseased coronary segments. METHODS AND RESULTS: Analysts of four European IVUS centres performed independent IVUS analyses (in total 7,188 cross-sectional analyses) and obtained volumetric data to evaluate the reproducibility of volumetric VH-IVUS measurements in 36 coronary segments (length 20.0+/-0.4 mm) from patients with stable angina. Geometric and compositional VH-IVUS measurements were highly correlated for the different comparisons. Overall intraclass correlation for vessel, lumen, plaque volume and plaque burden were 0.98, 0.92 0.95, and 0.86, respectively; for fibrous, fibro-lipidic, necrotic core and calcified volumes overall intraclass correlations were 0.95, 0.93, 0.99, and 1.00, respectively. There were significant but small differences for vessel, lumen, fibrous and calcified volumes, and there was no significant difference for plaque volume. Of the plaque components necrotic core and calcified volume showed on average the highest reproducibility. CONCLUSIONS: These findings underline the necessity to centrally analyse IVUS data obtained in multicentre studies addressing mild-to-moderately diseased coronary arteries. In addition, pooling VH-IVUS data from different studies, analysed at different centres, may be problematical.

Impact of analyzing less image frames per segment for radiofrequency-based volumetric intravascular ultrasound measurements in mild-to-moderate coronary atherosclerosis.

Volumetric radiofrequency-based intravascular ultrasound (RF-IVUS) data of coronary segments are increasingly used as endpoints in serial trials of novel anti-atherosclerotic therapies. In a relatively time-consuming process, vessel and lumen contours are defined; these contours are first automatically detected, then visually checked, and finally (in most cases) manually edited to generate reliable volumetric data of vessel geometry and plaque composition. Reduction in number of cross-sectional images for volumetric analysis could save analysis time but may also increase measurement variability of volumetric data. To assess whether a 50% reduction in number of frames per segment (every second frame) alters the reproducibility of volumetric measurements, we performed repeated RF-IVUS analyses of 15 coronary segments with mild-to-moderate atherosclerosis (20.2 +/- 0.2 mm-long segments with 46 +/- 13% plaque burden). Volumes were calculated based on a total of 731 image frames. Reducing the number of cross-sectional image frames for volumetric measurements saved analysis time (38 +/- 9 vs. 68 +/- 17 min/segment; P < 0.0001) and resulted for only a few parameters in (borderline) significant but mild differences versus measurements based on all frames (fibrous volume, P < 0.05; necrotic-core volume, P = 0.07). Compared to the intra-observer variability, there was a mild increase in measurement variability for most geometrical and compositional volumetric RF-IVUS parameters. In RF-IVUS studies of mild-to-moderate coronary disease, analyzing less image frames saved analysis time, left most volumetric parameters greatly unaffected, and resulted in a no more than mild increase in measurement variability of volumetric data.

Reproducibility of volumetric intravascular ultrasound radiofrequency-based analysis of coronary plaque composition in vivo.

Intravascular ultrasound radiofrequency (RF-IVUS) data permit the analysis of coronary plaque composition in vivo and is used as an endpoint of ongoing pharmacological intervention trials. We assessed the reproducibility of volumetric RF-IVUS analyses in mild-to-moderately diseased atherosclerotic human coronary arteries in vivo. A total of 9,212 IVUS analyses on cross-sectional IVUS frames was performed to evaluate the reproducibility of volumetric RF-IVUS measurements in 33 coronary segments with a length of 27 +/- 7 mm. For vessel, lumen, and plaque + media volume the relative measurement differences (P = NS for all) were (A = intraobserver comparison, same pullback) -0.40 +/- 1.0%; -0.48 +/- 1.4%; -0.35 +/- 1.6%, (B = intraobserver comparison, repeated pullback) -0.42 +/- 1.2%; -0.52 +/- 1.8%; -0.43 +/- 4.5% (C = interobserver comparison, same pullback) 0.71 +/- 1.8%; 0.71 +/- 2.2%, and 0.89 +/- 5.0%, respectively. For fibrous, fibro-lipidic, calcium, and necrotic-core volumes the relative measurement differences (P = NS for all) were (A) 0.45 +/- 2.1%; -1.12 +/- 4.9%; -0.84 +/- 2.1%; -0.22 +/- 1.8%, (B) 1.40 +/- 4.1%; 1.26 +/- 6.7%; 2.66 +/- 7.4%; 0.85 +/- 4.4%, and (C) -1.60 +/- 4.9%; 3.85 +/- 8.2%; 1.66 +/- 7.5%, and -1.58 +/- 4.7%, respectively. Of note, necrotic-core volume showed on average the lowest measurement variability. Thus, in mild-to-moderate atherosclerotic coronary artery disease the reproducibility of volumetric compositional RF-IVUS measurements from the same pullback is relatively high, but lower than the reproducibility of geometrical IVUS measurements. Measurements from repeated pullbacks and by different observers show acceptable reproducibilities; the volumetric measurement of the necrotic-core shows on average the highest reproducibility of the compositional RF-IVUS measurements.