Alistair C. Lindsay

Dynamic Changes of Edema and Late Gadolinium Enhancement after Acute Myocardial Infarction and Their Relationship to Functional Recovery and Salvage Index

Background— Changes in the myocardium in acute ischemia are dynamic and complex, and the characteristics of myocardial tissue on cardiovascular magnetic resonance in the acute setting are not fully defined. We investigated changes in edema and late gadolinium enhancement (LGE) with serial imaging early after acute myocardial infarction, relating these to global and segmental myocardial function at 6 months. Methods and Results— Cardiovascular magnetic resonance scans were performed on 30 patients with ST-elevation–myocardial infarction treated by primary percutaneous coronary intervention at each of 4 time points: 12 to 48 hours; 5 to 7 days; 14 to 17 days; and 6 months. All patients showed edema at 24 hours. The mean volume of edema (% left ventricle) was 37±16 at 24 hours and 39±17 at 1 week, with a reduction to 24±13 (P<0.01) by 2 weeks. Myocardial segments with edema also had increased signal on LGE at 24 hours (&kgr;=0.77; P<0.001). The volume of LGE decreased significantly between 24 hours and 6 months (27±15% versus 22±12%; P=0.002). Of segments showing LGE at 24 hours, 50% showed resolution by 6 months. In segments with such a reduction in LGE, 65% also showed improved wall motion (P<0.0001). The area of LGE measured at 6 months correlated more strongly with troponin at 48 hours (r=0.9; P<0.01) than LGE at 24 hours (r=0.7). The difference in LGE between 24 hours and 6 months had profound effects on the calculation of salvage index (26±21% at 24 hours versus 42±23% at 6 months; P=0.02). Conclusions— Myocardial edema is maximal and constant over the first week after myocardial infarction, providing a stable window for the retrospective evaluation of area at risk. By contrast, myocardial areas with high signal intensity in LGE images recede over time with corresponding recovery of function, indicating that acutely detected LGE does not necessarily equate with irreversible injury and may severely underestimate salvaged myocardium.

Systemic and Vascular Oxidation Limits the Efficacy of Oral Tetrahydrobiopterin Treatment in Patients With Coronary Artery Disease

Background— The endothelial nitric oxide synthase cofactor tetrahydrobiopterin (BH4) plays a pivotal role in maintaining endothelial function in experimental vascular disease models and in humans. Augmentation of endogenous BH4 levels by oral BH4 treatment has been proposed as a potential therapeutic strategy in vascular disease states. We sought to determine the mechanisms relating exogenous BH4 to human vascular function and to determine oral BH4 pharmacokinetics in both plasma and vascular tissue in patients with coronary artery disease. Methods and Results— Forty-nine patients with coronary artery disease were randomized to receive low-dose (400 mg/d) or high-dose (700 mg/d) BH4 or placebo for 2 to 6 weeks before coronary artery bypass surgery. Vascular function was quantified by magnetic resonance imaging before and after treatment, along with plasma BH4 levels. Vascular superoxide, endothelial function, and BH4 levels were determined in segments of saphenous vein and internal mammary artery. Oral BH4 treatment significantly augmented BH4 levels in plasma and in saphenous vein (but not internal mammary artery) but also increased levels of the oxidation product dihydrobiopterin (BH2), which lacks endothelial nitric oxide synthase cofactor activity. There was no effect of BH4 treatment on vascular function or superoxide production. Supplementation of human vessels and blood with BH4 ex vivo revealed rapid oxidation of BH4 to BH2 with predominant BH2 uptake by vascular tissue. Conclusions— Oral BH4 treatment augments total biopterin levels in patients with established coronary artery disease but has no net effect on vascular redox state or endothelial function owing to systemic and vascular oxidation of BH4. Alternative strategies are required to target BH4-dependent endothelial function in established vascular disease states. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00423280.

Optical coherence tomography for guidance of distal cell recrossing in bifurcation stenting: choosing the right cell matters

AIMS The aim of this study was to assess the ability of optical coherence tomography (OCT) to guide recrossing during percutaneous coronary interventions in bifurcations and to reduce strut malapposition. METHODS AND RESULTS Fifty-two patients undergoing elective treatment of bifurcation lesions using provisional stenting as default strategy were included in the study. Patients were divided into two groups: OCT-guided stent recrossing (group 1, n=12), and angiography-guided recrossing (group 2, n=40). Malapposition in the various bifurcation segments was compared in the two groups, using propensity score analysis to correct for confounders. In 4/12 patients (33%) of the OCT-guided group after the first attempt to recross the stent towards the SB the wire was found to have crossed in a proximal cell, requiring a second and in one case a third attempt to successfully cross through a distal cell. Patients who were treated using OCT-guided recrossing had a significantly lower number of malapposed stent struts, especially in the quadrants towards the SB ostium (9.5%[7.5-17.4%] vs 42.3%[31.2-54.7%] in the angiography-guided group, p<0.0001). CONCLUSIONS The rate of strut malapposition was significantly reduced when OCT was used to confirm that wire recrossing was performed in a distal cell of the SB ostium.

Form to function: current and future roles for atherosclerosis imaging in drug development

There is a pressing need for robust imaging markers to assist in the development of drugs for the treatment of atherosclerosis. Conventional imaging methods provide quantitative and morphological data but may be inadequate for assessing a new generation of therapies that modify plaque biology directly. Here, we compare the main imaging modalities used to image atherosclerosis in the clinical-trial setting, and assess their ability to predict clinical outcomes for a given sample size. We consider how emerging molecular and cellular imaging techniques could offer the possibility to quantify changes in biological function at the level of the plaque, even without gross structural change.

Optical coherence tomography: from research to practice

Optical coherence tomography (OCT) is a high-resolution imaging technique with great versatility of applications. In cardiology, OCT has remained hitherto as a research tool for characterization of vulnerable plaques and evaluation of neointimal healing after stenting. However, OCT is now successfully applied in different clinical scenarios, and the introduction of frequency domain analysis simplified its application to the point it can be considered a potential alternative to intravascular ultrasound for clinical decision-making in some cases. This article reviews the use of OCT for assessment of lesion severity, characterization of acute coronary syndromes, guidance of intracoronary stenting, and evaluation of long-term results.

Optical coherence tomography for guidance in bifurcation lesion treatment.

Optical coherence tomography (OCT) has higher resolution than IVUS (approximately 10 times), with the potential to precisely measure lumen diameters in the variable geometry of a bifurcational lesion and to identify superficial lipid laden plaques and calcium, relevant to confirm the severity of the lumen obstruction before treatment and guide location and diameter of the stent. In addition, OCT produces fewer strut-induced artifacts and offers precise evaluation of strut apposition in a real-life clinical setting. The increase in the speed of image acquisition consequent to the introduction of frequency domain OCT allows rapid pull-back at a speed of 2 cm/sec, minimising the amount of contrast required to clear blood during image acquisition, with an average injection of 10-18 ml required for the maximal length currently available of 5.6 cm. This allows serial OCT acquisitions, typically before treatment if the lesion is not very severe and flow is expected to be present around the OCT catheter, after predilatation and to assess and guide stent expansion. Repeated OCT examinations at follow-up may help to detect presence and characteristics of strut coverage, a potential predictor of late stent thrombosis. These applications are of particular interest in the context of bifurcational lesion treatment because this condition is still associated with a higher number of malapposed stent struts and frequent impairment of stent expansion, explaining the higher incidence of stent thrombosis and restenosis. In this article, all potential applications of OCT for bifurcational lesion treatment are explored. The use of OCT to characterise plaque components, and to optimise stent expansion and strut apposition are first discussed in detail. The conclusion of the article highlights some future research and technological developments that promise to expand the role of OCT further still.

Increase in J-CTO lesion complexity score explains the disparity between recanalisation success and evolution of chronic total occlusion strategies: insights from a single-centre 10-year experience

Objective To investigate whether treatment of lesions of greater complexity is now undertaken and to assess the rates of procedural success per class of lesion complexity. Design Observational study. Setting Despite impressive progress in treatment strategies and equipment, the success rate of percutaneous coronary intervention for chronic total occlusion (CTO) has remained relatively stable. Participants 483 patients consecutively treated with CTO from 2003 to 2012. Main outcome measures The Multicenter CTO Registry of Japan (J-CTO) score was used to classify lesion complexity. The study population was subdivided into an early (period 1, n=288) and a late (period 2, n=195) period according to the routine implementation of novel techniques and advanced equipment. Results Period 2 was marked by more ‘difficult’ and ‘very difficult’ lesions (J-CTO grades 2 and 3) being attempted, with procedural success increasing from 68.4% to 88.1% (p<0.001) and from 42.0% to 78.9% (p<0.001), respectively. ‘Easy’ and ‘intermediate’ lesions (J-CTO grades 0 and 1) were less common, but with similarly high success rates (89.1% vs 96.6% (p=0.45) for easy, and 86.3% vs 86.1% (p=0.99) for intermediate). Period 2 was characterised by a trend for more successful procedures overall (by 6.1%, p=0.09). Procedural complications were similarly low in both periods. J-CTO score and technical era were identified as independent correlates of success in the total population by logistic regression analysis. Conclusions Advanced CTO techniques and equipment have resulted in an increase in the successful treatment of highly complex lesions. Total success rate did not substantially improve, as it was counterbalanced by the increased rate at which complex lesions were attempted.

In-vivo quantitative T2 mapping of carotid arteries in atherosclerotic patients: segmentation and T2 measurement of plaque components

BackgroundAtherosclerotic plaques in carotid arteries can be characterized in-vivo by multicontrast cardiovascular magnetic resonance (CMR), which has been thoroughly validated with histology. However, the non-quantitative nature of multicontrast CMR and the need for extensive post-acquisition interpretation limit the widespread clinical application of in-vivo CMR plaque characterization. Quantitative T2 mapping is a promising alternative since it can provide absolute physical measurements of plaque components that can be standardized among different CMR systems and widely adopted in multi-centre studies. The purpose of this study was to investigate the use of in-vivo T2 mapping for atherosclerotic plaque characterization by performing American Heart Association (AHA) plaque type classification, segmenting carotid T2 maps and measuring in-vivo T2 values of plaque components.MethodsThe carotid arteries of 15 atherosclerotic patients (11 males, 71 ± 10 years) were imaged at 3 T using the conventional multicontrast protocol and Multiple-Spin-Echo (Multi-SE). T2 maps of carotid arteries were generated by mono-exponential fitting to the series of images acquired by Multi-SE using nonlinear least-squares regression. Two reviewers independently classified carotid plaque types following the CMR-modified AHA scheme, one using multicontrast CMR and the other using T2 maps and time-of-flight (TOF) angiography. A semi-automated method based on Bayes classifiers segmented the T2 maps of carotid arteries into 4 classes: calcification, lipid-rich necrotic core (LRNC), fibrous tissue and recent IPH. Mean ± SD of the T2 values of voxels classified as LRNC, fibrous tissue and recent IPH were calculated.ResultsIn 37 images of carotid arteries from 15 patients, AHA plaque type classified by multicontrast CMR and by T2 maps (+ TOF) showed good agreement (76% of matching classifications and Cohen’s κ = 0.68). The T2 maps of 14 normal arteries were used to measure T2 of tunica intima and media (T2 = 54 ± 13 ms). From 11865 voxels in the T2 maps of 15 arteries with advanced atherosclerosis, 2394 voxels were classified by the segmentation algorithm as LRNC (T2 = 37 ± 5 ms) and 7511 voxels as fibrous tissue (T2 = 56 ± 9 ms); 192 voxels were identified as calcification and one recent IPH (236 voxels, T2 = 107 ± 25 ms) was detected on T2 maps and confirmed by multicontrast CMR.ConclusionsThis carotid CMR study shows the potential of in-vivo T2 mapping for atherosclerotic plaque characterization. Agreement between AHA plaque types classified by T2 maps (+TOF) and by conventional multicontrast CMR was good, and T2 measured in-vivo in LRNC, fibrous tissue and recent IPH demonstrated the ability to discriminate plaque components on T2 maps.

The biophysics of renal sympathetic denervation using radiofrequency energy

Renal sympathetic denervation is currently performed in the treatment of resistant hypertension by interventionists who otherwise do not typically use radio-frequency (RF) energy ablation in their clinical practice. Adequate RF lesion formation is dependent upon good electrode-tissue contact, power delivery, electrode-tissue interface temperature, target-tissue impedance and the size of the catheter’s active electrode. There is significant interplay between these variables and hence an appreciation of the biophysical determinants of RF lesion formation is required to provide effective and safe clinical care to our patients. In this review article, we summarize the biophysics of RF ablation and explain why and how complications of renal sympathetic denervation may occur and discuss methods to minimise them.

Frequency domain optical coherence tomography for guidance of coronary stenting

OBJECTIVE To evaluate the role of Frequency domain optical coherence tomography (FD-OCT) in guiding stent implantation procedures. METHODS Dragonfly-imaging catheter was used pre-intervention, after pre-dilatation or at various stages of stent deployment/post-dilatation to assess lesion severity, characteristics and guide stent expansion/apposition. RESULTS We performed 398 OCT pull-backs in 108 consecutive patients. The 371 pull-backs analysable, had an average length of 35 mm and encompassed 193 lesions (1.8 lesions per patient). Seventy-six percent of patient had AHA-ACC-class B-C lesions. In the pre-intervention group deferral of treatment was decided for 13/68 pullbacks (19.1%), whereas strategies different from conventional predilatation (e.g. thrombectomy, rotablator, cutting-balloon) were decided in 23 cases (33.8%). After full lesion dilatation 96 pullbacks (25.9%, pre-stenting group) were performed, 46 (47.9%) of which suggested proceeding directly with stenting while 50 (52.1%) suggesting further treatment. Out of the 207 pullbacks in post-stenting group, 29 (14%) suggested new stent implantation because of dissection or residual stenosis; 64 (30.9%) suggested further optimization with high pressure/larger-sized balloon. Average number of pull-backs per patient was 3.4 requiring 75.8 ± 19.3 ml of iopamidol. No major complications were observed. Five cases (4.6%) of contrast-induced nephropathy were reported. CONCLUSIONS Repeated examinations with FD-OCT can be safely used to guide stent selection and improve stent expansion and apposition.