Gaston A. Rodriguez-Granillo

Long-Term Safety and Efficacy of Percutaneous Coronary Intervention With Stenting and Coronary Artery Bypass Surgery for Multivessel Coronary Artery Disease: A Meta-Analysis With 5-Year Patient-Level Data From the ARTS, ERACI-II, MASS-II, and SoS Trials

Background— Randomized trials that studied clinical outcomes after percutaneous coronary intervention (PCI) with bare metal stenting versus coronary artery bypass grafting (CABG) are underpowered to properly assess safety end points like death, stroke, and myocardial infarction. Pooling data from randomized controlled trials increases the statistical power and allows better assessment of the treatment effect in high-risk subgroups. Methods and Results— We performed a pooled analysis of 3051 patients in 4 randomized trials evaluating the relative safety and efficacy of PCI with stenting and CABG at 5 years for the treatment of multivessel coronary artery disease. The primary end point was the composite end point of death, stroke, or myocardial infarction. The secondary end point was the occurrence of major adverse cardiac and cerebrovascular accidents, death, stroke, myocardial infarction, and repeat revascularization. We tested for heterogeneities in treatment effect in patient subgroups. At 5 years, the cumulative incidence of death, myocardial infarction, and stroke was similar in patients randomized to PCI with stenting versus CABG (16.7% versus 16.9%, respectively; hazard ratio, 1.04, 95% confidence interval, 0.86 to 1.27; P=0.69). Repeat revascularization, however, occurred significantly more frequently after PCI than CABG (29.0% versus 7.9%, respectively; hazard ratio, 0.23; 95% confidence interval, 0.18 to 0.29; P<0.001). Major adverse cardiac and cerebrovascular events were significantly higher in the PCI than the CABG group (39.2% versus 23.0%, respectively; hazard ratio, 0.53; 95% confidence interval, 0.45 to 0.61; P<0.001). No heterogeneity of treatment effect was found in the subgroups, including diabetic patients and those presenting with 3-vessel disease. Conclusions— In this pooled analysis of 4 randomized trials, PCI with stenting was associated with a long-term safety profile similar to that of CABG. However, as a result of persistently lower repeat revascularization rates in the CABG patients, overall major adverse cardiac and cerebrovascular event rates were significantly lower in the CABG group at 5 years.

Coronary artery remodelling is related to plaque composition

Objective: To assess the potential relation between plaque composition and vascular remodelling by using spectral analysis of intravascular ultrasound (IVUS) radiofrequency data. Methods and results: 41 coronary vessels with non-significant (< 50% diameter stenosis by angiography), ⩽ 20 mm, non-ostial lesions located in non-culprit vessels underwent IVUS interrogation. IVUS radiofrequency data obtained with a 30 MHz catheter, were analysed with IVUS virtual histology software. A remodelling index (RI) was calculated and divided into three groups. Lesions with RI ⩾ 1.05 were considered to have positive remodelling and lesions with RI ⩽ 0.95 were considered to have negative remodelling. Lesions with RI ⩾ 1.05 had a significantly larger lipid core than lesions with RI 0.96–1.04 and RI ⩽ 0.95 (22.1 (6.3) v 15.1 (7.6) v 6.6 (6.9), p < 0.0001). A positive correlation between lipid core and RI (r  =  0.83, p < 0.0001) and an inverse correlation between fibrous tissue and RI (r  =  −0.45, p  =  0.003) were also significant. All of the positively remodelled lesions were thin cap fibroatheroma or fibroatheromatous lesions, whereas negatively remodelled lesions had a more stable phenotype, with 64% having pathological intimal thickening, 29% being fibrocalcific lesions, and only 7% fibroatheromatous lesions (p < 0.0001). Conclusions: In this study, in vivo plaque composition and morphology assessed by spectral analysis of IVUS radiofrequency data were related to coronary artery remodelling.

A novel approach for quantitative analysis of intracoronary optical coherence tomography: High inter-observer agreement with computer-assisted contour detection

Objective: This study aims to examine observer‐related variability of quantitative optical coherence tomography (OCT) derived measurements from both in vitro and in vivo pullback data. Background: Intravascular OCT is a new imaging modality using infrared light and offering 10 times higher image resolution (15 μm) compared to intravascular ultrasound. The quantitative analysis of in vivo intracoronary OCT imaging is complicated by the presence of blood, motion artifacts and the large quantity of information that has to be processed. Methods: We developed a standardized, automated quantification process for intracoronary OCT pullback data with inter‐observer variability assessed both in vitro by using postmortem human coronary arteries and in vivo by studying simple and complex coronary pathology and outcomes following stent implantation. The consensus between measurements by two observers was analyzed using the intraclass and interclass correlation coefficient and the reliability coefficients. Bland–Altman plots were generated to assess the relationship between variability and absolute measurements. Results: In vitro OCT assessment was performed in nine postmortem coronary arteries. The time needed for semiautomated contour detection of a 15‐mm long coronary segment was ∼40 min. The absolute and relative difference between lumen area measurements derived from two observers was low [0.02 ± 0.10 mm2; (0.3 ± 0.5)% respectively] with excellent correlation confirmed by linear regression analysis (R2 = 0.99; P < 0.001). Similarly, in vivo measurements demonstrated a high correlation with the main source of inter‐observer variation occurring as a result of coronary dissection and motion artifact. The absolute and relative difference between measurements were 0.11 ± 0.33 mm2 (1.57 ± 0.05)% for lumen area (R2 = 0.98; P < 0.001), 0.17 ± 0.68 mm2 (1.44 ± 0.08)% for stent area (R2 = 0.94; P < 0.001), and 0.26 ± 0.72 mm2 (14.08 ± 0.37)% for neointimal area (R2 = 0.78; P < 0.001). Conclusions: Highly accurate computer‐assisted quantitative analysis ofintracoronary OCT pullbacks is feasible with low inter‐observer variability. The presented approach allows for observer independent analysis of detailed vessel structures, and may be a valuable tool for future longitudinal studies incorporating OCT.

Early Assessment of Myocardial Viability by the Use of Delayed Enhancement Computed Tomography After Primary Percutaneous Coronary Intervention

OBJECTIVES We sought to explore the relationship between established parameters of reperfusion and the extent of myocardial damage measured by the delayed enhancement (DE) of iodinated contrast by multidetector computed tomography (MDCT) immediately after primary percutaneous coronary intervention (PCI). BACKGROUND Early detection of myocardial viability should be valuable for risk stratification of patients with reperfused acute myocardial infarction (AMI). METHODS Consecutive patients without a history of previous AMI who underwent primary PCI for an ST-segment elevation AMI were examined by DE-MDCT without an additional contrast injection immediately after completion of PCI. No medication was administrated to lower the heart rate. Dose modulation lead to an approximate mean radiation dose of 5.5 mSv. RESULTS Thirty patients constituted the study population. Mean age was 61.4 +/- 15.6 years, 24 (80%) were men, and 4 (13%) were diabetic. Although post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 was achieved in all patients, DE was detected in 14 (47%) patients. Age, sex, hypertension, diabetes, smoking history, serum creatinine levels, and pain duration were not associated with the presence of DE. Door-to-balloon time (DE 70.3 +/- 33.6 min vs. non-DE 98.3 +/- 70.7 min, p = 0.19) and lesion crossing time (DE 18.6 +/- 11.4 min vs. non-DE 16.4 +/- 9.6 min, p = 0.58) did not differ between groups. The TIMI myocardial perfusion grade (0 to 1 vs. 2 to 3) after stent implantation and electrocardiogram ST-segment resolution (<50% or >/=50%) were associated with the presence of DE (p = 0.001 and p = 0.02, respectively). Pre-discharge left ventricular ejection fraction was lower in DE than in non-DE patients (44.6 +/- 12.4% vs. 54.1 +/- 10.3%, respectively, p = 0.05). Hospitalization days (DE 5.6 +/- 3.8 vs. non-DE 4.8 +/- 1.0, p = 0.41) and 6-month cardiac events (DE 3 of 14 vs. non-DE 1 of 16, p = 0.22) did not differ between groups. CONCLUSIONS Early detection of myocardial viability immediately after primary PCI by the use of DE-MDCT is related to clinical and angiographic parameters of myocardial reperfusion.

In vivo Variability in Quantitative Coronary Ultrasound and Tissue Characterization Measurements with Mechanical and Phased-array Catheters

Background: Both mechanical and phased-array catheters are used in clinical trials to assess quantitative parameters. Only limited evaluation of the in vivo agreement of volumetrical measurements between such systems has been performed, despite the fact that such information is essential for the conduction of atherosclerosis regression trials. Methods and results: We prospectively evaluated the agreement in morphometric measurements and intravascular ultrasound (IVUS)-based plaque characterization between a 40 MHz rotating transducer (3.2 F Atlantis, Boston Scientific Corp.) and a 20 MHz phased-array catheter (2.9 F Eagle Eye, Volcano Therapeutics, Rancho Cordova, California) in 16 patients. Lumen (7.3 ± 2.0 mm2 vs. 6.7 ± 1.8 mm2, p = 0.001) and vessel (11.8 ± 3.3 mm2 vs. 11.0 ± 2.9 mm2, p = 0.02) cross-sectional areas (CSA) were significantly greater with the 20 MHz system. Plaque CSA measurements showed no significant difference between systems (4.4 ± 2.3 mm2 vs. 4.4 ± 2.1). The relative differences were less than 10% for the three variables. On IVUS-based tissue characterization (13 patients), calculated percentage hypoechogenic volume was significantly higher for the 20 MHz system (96.7 ± 2.38 vs. 88.4 ± 5.53, p < 0.0001). Conclusions: Quantitative IVUS analyses display significant catheter type-dependent variability. It is unclear whether the variability reflects overestimation of measurements with the phased-array or underestimation with the mechanical system. Although plaque burden measurements did not differ significantly between systems, it appears prudent to recommend the use of a single system for progression/regression studies.

Geometrical validation of intravascular ultrasound radiofrequency data analysis (Virtual Histology) acquired with a 30 MHz boston scientific corporation imaging catheter.

Recently, the plaque characterization field was explored with the use of the substrate (frequency domain analysis) rather than the envelope (amplitude or gray‐scale imaging) of the intravascular ultrasound (IVUS) radiofrequency data. However, there is no data about the agreement of quantitative outcome between the two methods. The aim of this study was to assess the correlation and agreement between quantitative coronary ultrasound and the geometrical measurements provided by the spectral analysis of ultrasound radiofrequency data [IVUS‐Virtual Histology (IVUS‐VH), Volcano Therapeutics). Twenty‐five patients were included in this study. The IVUS catheter used was a commercially available mechanical sector scanner (Ultracross 2.9 Fr 30 MHz catheter, Boston Scientific) covered with an outer sheath. IVUS‐VH significantly underestimated lumen [relative difference (RD) = 14.8 ± 5.6; P < 0.001], vessel (RD = 14.1 ± 4.8; P < 0.001), and plaque (RD = 11.5 ± 10.8; P < 0.001) cross‐sectional areas (CSAs). Nevertheless, when adjusted for the ultrasound propagation delay caused by the sheath, relative differences of measurements were remarkably low (0.49% ± 6.3%, P = 0.64 for lumen; 2.33% ± 4.6%, P = 0.007 for vessel; and 4.2% ± 10.4%, P = 0.005 for plaque CSA). These data suggest that the volumetric output of the IVUS‐VH software underestimates measurements when acquired with a 30 MHz catheter. However, after applying a mathematical adjustment method for the ultrasound propagation delay caused by the outer sheath of the 30 MHz catheter, relative differences of direct measurements were negligible. These results suggest that ultrasound radiofrequency data analysis could provide, aside from precise compositional data, an accurate geometrical output.

Incremental value of myocardial perfusion over coronary angiography by spectral computed tomography in patients with intermediate to high likelihood of coronary artery disease

PURPOSE We sought to explore the diagnostic performance of dual energy computed tomography (DECT) for the evaluation of myocardial perfusion in patients with intermediate to high likelihood of coronary artery disease (CAD). MATERIALS AND METHODS Consecutive patients with known or suspected CAD referred for myocardial perfusion imaging by single-photon emission computed tomography (SPECT) constituted the study population and were scanned using a DECT scanner equipped with gemstone detectors for spectral imaging, and a SPECT. The same pharmacological stress was used for both scans. RESULTS Twenty-five patients were prospectively included in the study protocol. The mean age was 63.4±10.6 years. The total mean effective radiation dose was 7.5±1.2 mSv with DECT and 8.2±1.7 mSv with SPECT (p=0.007). A total of 425 left ventricular segments were evaluated by DECT, showing a reliable accuracy for the detection of reversible perfusion defects [area under ROC curve (AUC) 0.84 (0.80-0.87)]. Furthermore, adding stress myocardial perfusion provided a significant incremental value over anatomical evaluation alone by computed tomography coronary angiography [AUC 0.70 (0.65-0.74), p=0.003]. CONCLUSIONS In this pilot investigation, stress myocardial perfusion by DECT demonstrated a significant incremental value over anatomical evaluation alone by CTCA for the detection of reversible perfusion defects.

Methodological considerations and approach to cross-technique comparisons using in vivo coronary plaque characterization based on intravascular ultrasound radiofrequency data analysis: insights from the Integrated Biomarker and Imaging Study (IBIS).

Grey scale intravascular ultrasound (IVUS) is a valuable clinical tool to assess the extent and severity of coronary atheroma. However, it cannot reliably identify plaques with a high‐risk of future clinical events. Serial IVUS studies to assess the progression and/or regression of atherosclerotic plaques demonstrated only modest effects, of pharmacological intervention on plaque burden, even when clinical efficacy is documented. Spectral analysis of radiofrequency ultrasound data (IVUS‐virtual histologyTM (IVUS‐VH), Volcano Therapeutics, Rancho Cordova, CA) has the potential to characterize accurately plaque composition. The Integrated Biomarker and Imaging Study (IBIS) evaluated both invasive and non‐invasive imaging techniques along with the assessment of novel biomarkers to characterize sub‐clinical atherosclerosis. IVUS‐VH was not included at the start of the IBIS protocol. The purpose of this paper is to describe the methodology we used to obtain and analyse IVUS‐VH images and the approach to cross‐correlations with the other techniques.

Monochromatic image reconstruction by dual energy imaging allows half iodine load computed tomography coronary angiography

PURPOSE To compare image interpretability and diagnostic performance of dual-energy CT coronary angiography (DE-CTCA) performed with 50% iodine load reduction versus single energy acquisitions (SE-CTCA) with full iodine load. MATERIALS AND METHODS The present prospective study involved patients with suspected coronary artery disease (CAD) clinically referred for CTCA. DE-CTCA with 50% iodine volume load was performed first, and after heart rate returned to baseline SE-CTCA was performed using full iodine volume load. The primary endpoint was to compare image interpretability between groups. DE-CTCA was performed by rapid switching between low and high tube potentials (80-140 kV) from a single source, allowing the generation of monochromatic image reconstructions ranging from 40 to 140 keV. Image quality assessment was performed using a 5-point Likert scale. RESULTS Thirty-six patients constituted the study population. The mean heart rate before the CT scan (DE-CTCA 57.3 ± 10.7 bpm vs. SE-CTCA 58.5 ± 11.2 bpm, p=0.29) and the mean effective radiation dose (3.5 ± 1.9 mSv vs. 3.8 ± 0.9 mSv, p=0.48) did not differ between groups. Likert image quality scores were similar between groups (DE-CTCA 4.42 ± 0.98 vs. SE-CTCA 4.43 ± 0.84, p=0.67). Signal-to-noise and contrast-to-noise ratios were significantly lower with DE-CTCA, driven by lower signal density levels at 60 keV compared to SE-CTCA. The sensitivity and specificity for the detection of stenosis >50% was indistinguishable between groups (DE-CTCA 84.4% (69.9-93.0%), 87.1% (81.6-91.2%); SE-CTCA 84.4% (69.9-93.0%), 87.1% (81.6-91.2%). CONCLUSIONS In this pilot, prospective study, dual energy CTCA imaging with half iodine load achieved comparable interpretability than full iodine load with single energy CTCA.

Advantages and disadvantages of biodegradable platforms in drug eluting stents

Coronary angioplasty with drug-eluting stent (DES) implantation is currently the most common stent procedure worldwide. Since the introduction of DES, coronary restenosis as well as the incidence of target vessel and target lesion revascularization have been significantly reduced. However, the incidence of very late stent thrombosis beyond the first year after stent deployment has more commonly been linked to DES than to bare-metal stent (BMS) implantation. Several factors have been associated with very late stent thrombosis after DES implantation, such as delayed healing, inflammation, stent mal-apposition and endothelial dysfunction. Some of these adverse events were associated with the presence of durable polymers, which were essential to allow the elution of the immunosuppressive drug in the first DES designs. The introduction of erodable polymers in DES technology has provided the potential to complete the degradation of the polymer simultaneously or immediately after the release of the immunosuppressive drug, after which a BMS remains in place. Several DES designs with biodegradable (BIO) polymers have been introduced in preclinical and clinical studies, including randomized trials. In this review, we analyze the clinical results from 6 observational and randomized studies with BIO polymers and discuss advantages and disadvantages of this new technology.