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A novel biomarker panel was proposed to quantify macro and microstructural biomarkers from the normal- appearing brain matter (NABM) in multicentre fluid-attenuation inversion recovery (FLAIR) MRI. The NABM is composed of the white and gray matter regions of the brain, with the lesions and cerebrospinal fluid removed. The primary hypothesis was that NABM biomarkers from FLAIR MRI are related to cognitive outcome as determined by MoCA score. There were three groups of features designed for this task based on 1) texture: microstructural integrity (MII), macrostructural damage (MAD), microstructural damage (MID), 2) intensity: median, skewness, kurtosis and 3) volume: NABM to ICV volume ratio. Biomarkers were extracted from over 1400 imaging volumes from more than 87 centres and unadjusted ANOVA analysis revealed significant differences in means of the MII, MAD, and NABM volume biomarkers across all cognitive groups. In an adjusted ANCOVA model, a significant relationship between MoCA categories was found that was dependent on subject age for MII, MAD, intensity, kurtosis and NABM volume biomarkers. These results demonstrate that structural brain changes in the NABM are related to cognitive outcome (with different relationships depending on the age of the subjects). Therefore these biomarkers have high potential for clinical translation. As a secondary hypothesis, we investigated whether texture features from FLAIR MRI can quantify microstructural changes related to how “structured” or “damaged” the tissue is. Based on correlation analysis with diffusion weighted MRI (dMRI), it was shown that FLAIR MRI texture biomarkers (MII and MAD) had strong correlations to mean diffusivity (MD) which is related to tissue degeneration in the GM and WM regions. As FLAIR MRI is routinely collected for clinical neurological examinations, novel biomarkers from FLAIR MRI could be used to supplement current clinical biomarkers and for monitoring disease progression. Biomarkers could also be used to stratify patients into homogeneous disease subgroups for clinical trials, or to learn more about mechanistic development of dementia disease.

The study of anatomical irregularities in tree rings has recently gained momentum as a complement to traditional tree-ring measurements as they may provide information on extreme climatic events. Two anomalies, blue rings (BR) and frost rings (FR), were analyzed in bristlecone pine (Pinus longaeva D.K. Bailey) trees located along an elevation gradient in northeastern Nevada. These two subannual ring anomalies were systematically compiled for two periods; one centered on 536 CE (well-known for a volcanically-induced period of climatic cooling) and the other on 1965 CE (useful due to the availability of instrumental climate data). During the period 523–545 CE (n ≥ 10 trees), both BR and latewood FR (LWFR) were recorded abundantly in 532 and 536, as well as a BR cluster from 539 to 542 CE. Years when trees solely recorded a BR (without an accompanying LWFR) were more frequent in the earlier period than in the modern period (1954–2006 CE; n ≥ 10 trees) when both anomalies tended to co-occur. These results suggest a shorter growing season in the 536 period than in the 20th century. Modern BR/LWFR were most abundant in 1965 and 1978 CE. Both anomalies were mainly observed in the highest elevation trees and both were produced in years characterized by cooler than average temperatures throughout the growing season. Anatomically, BR and LWFR did not differ significantly in tracheid dimensions except that LWFR clearly showed damages associated with sub-freezing temperatures. The main feature distinguishing BR and LWFR from “normal” tree rings was a significant reduction in latewood secondary wall thickness. In P. longaeva, BR like pale latewood (light) rings, result from short and cool growing seasons which leads to reduced (or interrupted) lignification of tracheids. In species producing extremely narrow latewood like P. longaeva it may be difficult to macroscopically identify pale latewood years, thus rendering microscopic investigation of BR as a climate proxy useful in paleoclimatic research.

Psoriasis is a chronic immune-mediated disease with a prevalence as high as 3%. Several studies have reported that psoriasis is an independent risk factor for myocardial infarction, however some studies failed to show an increased risk of myocardial infarction in patients with psoriasis and the subject remains controversial. This article is protected by copyright. All rights reserved.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Background and purpose: Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A-I (ApoA-I) mimetic peptide infusions could induce regression of AVS. Experimental approach: Fifteen New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D2 until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline (control group, n=8) or an ApoA-I mimetic peptide (treated group, n=7), three times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed. Key results: Aortic valve area increased significantly by 25% in the treated group after 14 days of treatment (P=0.012). Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls (P=0.0006). Histological analysis revealed that the extent of lesions at the base of valve leaflets and sinuses of Valsalva was smaller in the treated group compared with controls (P=0.032). The treatment also reduced calcification, as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcification area and aortic valve thickness. Conclusions and implications: Infusions of ApoA-I mimetic peptide lead to regression of experimental AVS. These positive results justify the further testing of high-density lipoprotein (HDL)-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform the clinical treatment of this disease. British Journal of Pharmacology (2008) 154, 765–773; doi:10.1038/bjp.2008.122; published online 14 April 2008

Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to ‘treat IMT values’ nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

Background In the Determining the Efficacy and Tolerability of cholesteryl ester transfer protein (CETP) INhibition with AnacEtrapib (DEFINE) trial, anacetrapib added to statin produced robust low-density lipoprotein cholesterol (LDL-C)-lowering and high-density lipoprotein cholesterol (HDL-C)-raising vs placebo in patients with coronary heart disease (CHD). Predictors of the degree of LDL-C and HDL-C responses to anacetrapib, however, are poorly understood. Objective Lipid effects of anacetrapib in patient subgroups within the DEFINE trial (clinicaltrials.gov: NCT00685776) are reported. Methods The percent of placebo-corrected changes from baseline for LDL-C (estimated by Friedewald calculation [Fc-LDL-C]) and HDL-C after 24 weeks of anacetrapib 100 mg/day were compared among patients by age, gender, race, diabetes status, type of concomitant statin with or without other lipid therapies, and baseline HDL-C, Fc-LDL-C, and triglyceride (TG) levels. Results Percent decreases in Fc-LDL-C and increases in HDL-C with anacetrapib were similar (magnitude of difference generally

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

Accurate simulation of blood hemolytic potential (i.e. the destruction of red blood cells) would be a valuable tool to evaluate blood-interacting devices. Indeed, such a model would alleviate several practical problems with manipulating real blood (addition of anticoagulants and antibiotics, filtration, etc.). In the present study, we have developed a blood analog which is a suspension of micron-sized natural polymeric gel particles, each encapsulating a dye agent. These particles release the dye agent through shear-induced diffusion and fragmentation from exposure to high, non-physiological shear rates. A controlled shear field was applied to blood analog samples using a custom-made grooved parallel plate geometry device as previously reported in the literature. The device was designed to apply a shear stress and shear exposure duration in the range of 0.15 – 269.18 Pa and 156 - 1297 ms, respectively. From the results obtained, a correlation between the human index of hemolysis and the concentration of the released dye agent can be found. Therefore, the use of the proposed suspensions appears suitable as a blood analog for the in vitro evaluation of the destructive effects of cardiovascular devices.

Recent data suggest that masked hypertension (MH) carries a cardiovascular risk similar to that of uncontrolled hypertension.The objective of this study was to determine the prevalence and determinants of MH in patients treated for hypertension in a Canadian primary care setting.Office blood pressure (OBP) was measured at baseline and after 3 months of valsartan-based therapy in 5636 hypertensive patients who had recorded their home blood pressure monitoring (HBPM) for seven consecutive days at month 3 using an Omron HEM-711 apparatus. MH was defined in nondiabetic patients as an OBP140/90 mmHg and an HBPM ≥135/85 mmHg, and in those with diabetes as an OBP130/80 mmHg and an HBPM ≥125/75 mmHg.Of the 5636 patients, 1025 had diabetes. OBP was controlled at 3 months in 268 (26.1%) of them, but 167 (62.3%) had MH. OBP was controlled in 2728 (59.1%) of the 4611 patients without diabetes, and 935 (34.3%) of them had MH. Overall, 1102 patients had MH, representing 36.8% of patients with controlled OBP and 19.6% of the entire hypertensive study population. Stepwise multiple logistic regression analysis in nondiabetic patients with controlled OBP at 3 months revealed that older age, male sex, higher body mass index and higher office systolic blood pressure were determinants of MH.Our results indicate that one of five hypertensive patients and more than one of three with controlled OBP will have MH. MH is associated with other cardiovascular risk factors, such as diabetes, and in nondiabetics, with male sex, older age and obesity.

Aortic cross-clamp time remains a significant marker of mortality and morbidity after coronary artery bypass graft (CABG) surgery. Pyridoxal-5-phosphate (MC-1), blocking purinergic receptors and intracellular influx of calcium, was shown to decrease the incidence of perioperative myocardial infarction in the prospective, randomized, double-blinded MC-1 to Eliminate Necrosis and Damage in CABG (MEND-CABG) clinical trial.We studied the relationship between treatment with MC-1 and aortic cross-clamping relative to the incidence of cardiovascular (CV) death and myocardial infarction (MI) in the trial that enrolled 901 high-risk patients undergoing CABG with cardiopulmonary bypass. Patients were randomized to receive either placebo, MC-1 250 mg/day or MC-1 750 mg/day starting 3-10 h before CABG and continued for 30 days after surgery. Serial creatine kinase-myocardial band (CK-MB) determinations, ECGs and clinical evaluations were performed.Cross-clamping time increased the event rate of death and MI with an odds ratio (95% confidence interval) of 1.67 (1.17-2.37, P=0.0044). Treatment with MC-1 decreased the rate of events (P=0.0073) with odds ratios of 0.52 (0.31-0.88 for MC-1 250 mg/day versus placebo) and 0.48 (0.29-0.82 for MC-1 750 mg/day versus placebo). There was no interaction between cross-clamp time and treatment (P=0.61) on the occurrence of the combined endpoint.MC-1 decreased the incidence of CV death and MI (CK-MBor=100 ng/mL) during the first 90 days after CABG in the MEND-CABG trial. Although longer aortic clamping time increased the risk of cardiovascular events, the protective effect of MC-1 was independent of ischemic time during CABG.

Aortic valve stenosis (AVS) is the most common valvular heart disease, and standard curative therapy remains open heart surgical valve replacement. The aim of our experimental study was to determine if apolipoprotein A-I (ApoA-I) mimetic peptide infusions could induce regression of AVS.Fifteen New Zealand White male rabbits received a cholesterol-enriched diet and vitamin D(2) until significant AVS was detected by echocardiography. The enriched diet was then stopped to mimic cholesterol-lowering therapy and animals were allocated randomly to receive saline (control group, n=8) or an ApoA-I mimetic peptide (treated group, n=7), three times per week for 2 weeks. Serial echocardiograms and post mortem valve histology were performed.Aortic valve area increased significantly by 25% in the treated group after 14 days of treatment (P=0.012). Likewise, aortic valve thickness decreased by 21% in the treated group, whereas it was unchanged in controls (P=0.0006). Histological analysis revealed that the extent of lesions at the base of valve leaflets and sinuses of Valsalva was smaller in the treated group compared with controls (P=0.032). The treatment also reduced calcification, as revealed by the loss of the positive relationship observed in the control group (r=0.87, P=0.004) between calcification area and aortic valve thickness.Infusions of ApoA-I mimetic peptide lead to regression of experimental AVS. These positive results justify the further testing of high-density lipoprotein (HDL)-based therapies in patients with valvular aortic stenosis. Regression of aortic stenosis, if achieved safely, could transform the clinical treatment of this disease.

Intima-media thickness (IMT) is increasingly used as a surrogate end point of vascular outcomes in clinical trials aimed at determining the success of interventions that lower risk factors for atherosclerosis and associated diseases (stroke, myocardial infarction and peripheral artery diseases). The necessity to promote further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT and to standardize IMT measurements is expressed through this updated consensus. Plaque is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. Standard use of IMT measurements is based on physics, technical and disease-related principles as well as agreements on how to perform, interpret and document study results. Harmonization of carotid image acquisition and analysis is needed for the comparison of the IMT results obtained from epidemiological and interventional studies around the world. The consensus concludes that there is no need to 'treat IMT values' nor to monitor IMT values in individual patients apart from exceptions named, which emphasize that inside randomized clinical trials should be performed. Although IMT has been suggested to represent an important risk marker, according to the current evidence it does not fulfill the characteristics of an accepted risk factor. Standardized methods recommended in this consensus statement will foster homogenous data collection and analysis. This will help to improve the power of randomized clinical trials incorporating IMT measurements and to facilitate the merging of large databases for meta-analyses.

Intravascular ultrasound (IVUS) is an imaging modality that experienced a tremendous development over the last 20 years. Phantoms for IVUS are rare and poorly documented. The aim of this paper is to propose an original IVUS phantom that has geometries and specular textures closer to those of coronary arteries than conventional tube-like phantoms. The proposed phantom has a three-layer aspect, reproducing the intima, media and adventitia that compose the arterial wall. It is made of an agar-based compound, with water, glycerol and cellulose particles. Fourteen phantoms were quantified using IVUS. Six phantoms were evaluated by both photomacroscopy and IVUS. There was an excellent correlation between phantom dimensions evaluated by photomacroscopy and the nominal values (mold dimensions). The IVUS quantification of the phantom was closely correlated to the measurements obtained by photomacroscopy. These results demonstrate that a multilayer phantom, with known and reproducible dimensions and with realistic geometric and echographic properties has been developed.

Intracoronary ultrasound (ICUS) imaging uses miniaturized transducers at the tip of catheters to supply tomographic, cross-sectional images of coronary arteries [1, 2]. ICUS provides detailed information not only on the degree of arterial stenosis but also on the atherosclerotic lesions and the vessel wall [3]. The traditional angiographic approach used to evaluate coronary artery disease has well-known limitations. One shortcoming is that coronary angiography provides only a planar perspective of the arterial lumen. Depiction of the coronary lumen, and not the wall, is another important limitation of angiography, atherosclerosis being primarily a disease of the arterial wall. The severity of stenosis may be underestimated by angiography because the reference segment used to quantitate the lesion is involved in the diffuse atherosclerotic process. In addition, the composition and morphology of atherosclerotic lesions, which cannot be assessed with angiography, are major determinants of the clinical expression of coronary atherosclerosis and of the response to percutaneous interventions.

Both mechanical and multi-element intravascular ultrasound designs have potential advantages and limitations that may impact on their value for clinical and research purposes. Determination of the reproducibility of measurements is critical before a given system can be used in studies such as regression of atherosclerosis trials.We performed serial intravascular ultrasound imaging with catheters using mechanical and phased-array designs in stented and non-stented coronary arteries in dogs and in patients.Both systems correlated well for areas (ror = 0.90, p0.0001) and diameters (ror = 0.84. p0.0001) in dogs and in patients. There was a slight difference between multi-element and mechanical designs for measurements of area (mean difference in dogs and in patients: -0.24 and 0.96 mm2, p0.055) and diameter (-0.08 and 0.16 mm, p0.0001). The reproducibility of the multi-element system for reanalysis of the same frames and for analysis of serial pullbacks was similar to the same measurements with the mechanical system (ror = 0.96 for all measurements). The differences in absolute and relative variability between the mechanical and phased-array designs, both for reanalysis of same frames and serial pullbacks, were very small.Although multi-element and mechanical intravascular ultrasound designs are not strictly interchangeable, their similar reproducibility and the small differences in measurements demonstrate that both designs are acceptable alternatives for trials of regression of atherosclerosis. Determination of the variability for serial pullbacks of both designs was also important to assess the statistical power of such trials.

It has been shown in the MultiVitamins and Probucol (MVP) trial that probucol reduces angiographic lumen loss by 68% after percutaneous transluminal coronary angioplasty (PTCA). Restenosis occurred in 40% of patients not treated with probucol and in 20% of those in the probucol alone group.To determine the morphological predictors of restenosis in patients treated with probucol.Beginning 30 days before angioplasty, 317 patients were randomly assigned to receive probucol, multivitamins, the combined treatment or placebo. Patients were then treated for six months after angioplasty. Intravascular ultrasound (IVUS) examination was performed immediately after angioplasty and at follow-up in 94 patients (108 segments). The angioplasty operator was blinded to the IVUS results. The cross-section selected for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. Receiver operating characteristic curves were used to determine the performance of criteria to predict angiographic restenosis at follow-up.In probucol-treated patients, the cross-sectional area (CSA) narrowing of 67.6% or less was the best IVUS predictor for the absence of restenosis (P=0.03). Diameter stenosis of 35% or less almost reached significance as a predictor in these patients (P=0.056). The restenosis rate when either of these predictors was met was less than 13%. Rates of repeat PTCA in patients treated with probucol were 9.7% when CSA narrowing was 67.6% or less on IVUS and 3.1% with a post-PTCA stenosis of 35% or less on quantitative coronary angiography (QCA). No predictor of the absence of restenosis in patients not treated with probucol was identified.The presence after balloon angioplasty of a CSA narrowing of 67.6% or less on IVUS or a diameter stenosis of 35% or less on QCA is associated, in patients treated with probucol, with extremely low rates of coronary restenosis and repeat angioplasty.

Stenosis severity may be underestimated by angiography because the reference segment used to quantify the lesion is itself narrowed by atherosclerotic plaque. Even assessment of the absolute change in lumen diameter on arteriography cannot consistently reflect changes in plaque burden because of the variable presence of vascular remodelling. Intravascular ultrasound (IVUS) differs radically from angiography by providing cross-sectional images of both the coronary arterial lumen and the wall with high resolution. The diffuse nature of coronary artery disease is readily seen and the majority of angiographically normal reference segments are involved in the atherosclerotic process on IVUS imaging. The precise assessment of plaque burden by IVUS makes it the ideal tool for a clinical trial of progression and regression of atherosclerosis.

To determine whether patients with cardiac tamponade are subject to delays and clinical deterioration before undergoing echocardiography and pericardial drainage.Retrospective study.The Montreal Heart Institute, Montreal, Quebec, a cardiology referral centre.The charts of 50 patients who presented with tamponade were reviewed. Intervals between the appearance of symptoms, consultation, echocardiography and drainage were noted. The presence of clinical deterioration before drainage was evaluated. Causes for delays were investigated.Previous cardiac surgery (74%) was the most common etiology of tamponade. Symptoms were present 6.6+/-5.8 days before consultation. The delay between consultation and echocardiography was 1.2+/-2.0 days (range 0 to 12), and that between echocardiography and drainage was 0.8+/-0.9 days (range 0 to four). Patients underwent drainage 1. 9+/-2.5 days (range 0 to 16) after the initial consultation. Deterioration of the clinical status was noted in 34% of patients before pericardial drainage. An error in the initial diagnosis was present in 36% of patients; the majority of these were incorrectly diagnosed with heart failure. Another 44% of patients had no mention of either a working diagnosis in the chart at admission or the desire to rule out tamponade on the request for echocardiography.The proper diagnosis does not appear to be initially considered in up to 80% of patients who present with cardiac tamponade. Clinical deterioration occurs in approximately a third of patients during the interval between consultation and pericardial drainage.

Endothelium-dependent vasodilation is impaired in asymptomatic subjects with risk factors for atherosclerosis.To determine whether a three-month integrative primary prevention program can improve endothelial function in asymptomatic subjects with risk factors for atherosclerosis.Twenty-two asymptomatic middle-aged men and women (13 men and nine women) aged 55 +/- 7 years with sedentary lifestyle and dyslipidemia (low density lipoprotein [LDL] level greater than 3.4 mmol/L) underwent an exercise test, determination of fasting blood lipid levels and noninvasive measurement of brachial artery reactivity before and three months after the beginning of a prevention program. The program consisted of exercise training (three times per week) and National Cholesterol Education Program step 1 diet in all subjects. A smoking cessation program was offered when applicable (six patients). Brachial artery diameter was measured by using high resolution ultrasound at rest, during reactive hyperemia (flow-mediated dilation [FMD], which is endothelium-dependent) and after sublingual nitroglycerin (NTG) (endothelium-independent vasodilation).After three months, peak oxygen uptake increased significantly from 25.4 +/- 4.9 to 27.5 +/- 4.8 mL/kg/min (P0.005), and LDL level decreased significantly from 4.48 +/- 0.92 to 4.00 +/- 0.83 mmol/L (P0.005). FMD and NTG responses assessed as percentage of diameter change from baseline, however, did not change (FMD 5.4 +/- 4.3% before and 5.1 +/- 3.9% at three months, not significant; NTG 8.4 +/- 3.8% before and 7.4 +/- 4.5% at three months, not significant).Short-term application of the currently recommended lifestyle intervention in adults with coronary risk factors did not improve vascular endothelial function. Longer and more aggressive programs may be needed to improve vascular function in subjects with risk factors for atherosclerosis.

Recently, the use of ionizing radiations has received much interest as a new treatment tool to reduce restenosis after angioplasty or stent implantation. There are two main approaches for delivering endovascular radiation: one is based on gamma or beta sources with very high activities to deliver locally through a catheter the dose in a limited period of time. The other approach is based on a stent rendered radioactive for long exposure and continuous low-dose rate treatment. External radiation is also contemplated but indications seem more oriented towards the peripheral vascular system. After a brief introduction to fundamentals of radiobiology, radiation physics and radioprotection, we review the experimental data which have led to large ongoing multicenter trials. The results of these trials involving more than 2000 patients will be available in the next few years and will allow to better define the risk/benefit ratio of this potentially new indication for radiotherapy.

We have shown that probucol reduces restenosis after balloon angioplasty. Whether probucol acted via prevention of neointimal formation or improvement in vascular remodeling could not be addressed by angiography and required the use of intravascular ultrasound (IVUS).Beginning 30 days before angioplasty, 317 patients were randomly assigned to receive probucol, multivitamins, combined treatment, or placebo. Patients were then treated for 6 months after angioplasty. IVUS examination was performed immediately after angioplasty and at follow-up in 94 patients (111 segments). The cross section selected for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. In the placebo group, lumen area decreased by -1. 21+/-1.88 mm2 at follow-up, and wall area and external elastic membrane (EEM) area increased by 1.50+/-2.50 and 0.29+/-2.93 mm2, respectively. Change in lumen area, however, correlated more strongly with the change in EEM area (r=0.53, P=0.002) than with the change in wall area (r=-0.13, P=0.49). Lumen loss was -1.21+/-1.88 mm2 for placebo, -0.83+/-1.22 mm2 for vitamins, -0.25+/-1.17 mm2 for combined treatment, and -0.15+/-1.70 mm2 for probucol alone (P=0.002 for probucol, P=0.84 for vitamins). Change in wall area was similar for all groups. EEM area increased by 0.29+/-2.93 mm2 for placebo, 0. 09+/-2.33 mm2 for vitamins only, 1.17+/-1.61 mm2 for combined treatment, and 1.74+/-1.80 mm2 for probucol only (P=0.005 for probucol).Lumen loss after balloon angioplasty is due to inadequate vessel remodeling in response to neointimal formation. Probucol exerts its antirestenotic effects by improving vascular remodeling after angioplasty.

A 72-year-old woman presented to hospital with rapidly progressive dyspnea and chest pain on exertion. Physical findings included a grade 3/6 systolic murmur increased by the Valsalva manoeuvre. Transthoracic echocardiography revealed concentric left ventricular hypertrophy, systolic anterior motion of the mitral valve and critical dynamic outflow tract obstruction. The myocardium was strikingly heterogeneous with hyperdynamic left ventricular systolic function. Laboratory findings included severe hypercalcemia secondary to primary hyperparathyroidism. The patient's outcome was unfavourable with nephrogenic diabetes insipidus, pancreatitis, shock, severe acidosis and death. Postmortem examination confirmed the presence of severe concentric left ventricular hypertrophy, a narrowed left ventricular outflow tract and localized endocardial fibrosis of the left interventricular septum. Microscopic findings showed diffuse calcium deposits of the myocardium, coronary arteries, kidneys and lungs. This appears to be the first report of two-dimensional and Doppler echocardiographic findings in hypercalcemic cardiomyopathy mimicking obstructive hypertrophic cardiomyopathy.

Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty.One month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach.The mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol).The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

Three patients were referred for suspicion of intracardiac tumour on transthoracic echocardiography. In all patients, the mass appeared as a nonobstructive oval structure measuring approximately 12 x 4 mm, located near the posterior third of the interatrial septum in the right atrium in the apical four-chamber view. The characteristics of the mass were not those of a Eustachian valve or a Chiari network. Multiplane transesophageal echocardiography performed in each of these patients did not reveal a tumour but rather a fibrous band in the right atrium, extending from the inferior to the superior vena cava. These findings are consistent with remnants of the right valve of the sinus venosus. Inclusion of a persistent right valve of the sinus venosus in the differential diagnosis of a right atrial mass can alleviate concern and spare an unnecessary transesophageal examination when the typical transthoracic echocardiographic characteristics are identified.

The purpose of this study was to determine the impact of changes in flow on aortic valve area (AVA) as measured by the Gorlin formula and transesophageal echocardiographic (TEE) planimetry.The meaning of flow-related changes in AVA calculations using the Gorlin formula in patients with aortic stenosis remains controversial. It has been suggested that flow dependence of the calculated area could be due to a true widening of the orifice as flow increases or to a disproportionate flow dependence of the formula itself. Alternatively, anatomic AVA can be measured by direct planimetry of the valve orifice with TEE.Simultaneous measurement of the planimetered and Gorlin valve area was performed intraoperatively under different hemodynamic conditions in 11 patients. Left ventricular and ascending aortic pressures were measured simultaneously after transventricular and aortic punctures. Changes in flow were induced by dobutamine infusion. Using multiplane TEE, AVA was planimetered at the level of the leaflet tips in the short-axis view.Overall, cardiac output, stroke volume and transvalvular volume flow rate ranged from 2.5 to 7.3 liters/min, from 43 to 86 ml and from 102 to 306 ml/min, respectively. During dobutamine infusion, cardiac-output increased by 42% and mean aortic valve gradient by 54%. When minimal flow was compared with maximal flow, the Gorlin area varied from (mean +/- SD) 0.44 +/- 0.12 to 0.60 +/- 0.14 cm2 (p0.005). The mean change in Gorlin area under different flow rates was 36 +/- 32%. Despite these changes, there was no significant change in the planimetered area when minimal flow was compared with maximal flow. The mean difference in planimetered area under different flow rates was 0.002 +/- 0.01 cm2 (p = 0.86).By simultaneous determination of Gorlin formula and TEE planimetry valve areas, we showed that acute changes in transvalvular volume flow substantially altered valve area calculated by the Gorlin formula but did not result in significant alterations of the anatomic valve area in aortic stenosis. These results suggest that the flow-related variation in the Gorlin AVA is due to a disproportionate flow dependence of the formula itself and not a true change in valve area.

Intravascular ultrasound (IVUS) is an imaging method which uses one or several ultrasound transducers at the tip of catheters to visualize the morphology of arteries. IVUS was developed to provide precise information not only about arterial stenoses, but also about atherosclerotic lesions and lesions of the vessel wall. Indications for IVUS are currently being developed. One application is for the evaluation of disease of the common trunk when a doubt persists after angiography. Ambiguous lesions on angiography, particularly situated at coronary bifurcations, can also be clarified by IVUS. The precise evaluation of the real extent of atherosclerosis by IVUS makes it an ideal tool for clinical trials of regression of coronary disease. It also provides a better understanding of the apparent paradox between the minimal reduction of atheromatous plaques on angiography and the dramatic reduction of coronary events. IVUS is extremely useful to elucidate the mechanisms and complications of percutaneous interventional procedures. For example, IVUS allows a better understanding of restenosis after angioplasty (whether it is due to intimal proliferation or to vascular remodelling), elastic recall and sudden occlusion. In view of the large atheromatous mass visible on IVUS at the dilated site even after an angiographically adequate operation, insufficient angioplasty can be considered to be the third mechanism contributing to restenosis. This finding has important clinical implications, as ultrasound guidance could possibly result in better short-term and medium-term results of angioplasty. IVUS could also allow better selection of the type of operation in these patients. IVUS is also useful to facilitate adequate deployment of coronary stents, as angiographic criteria predicting ultrasonographically adequate expansion of the stent have still not been developed. By complementing angiography for the diagnosis of atheromatous disease and by monitoring percutaneous coronary operations, the role of IVUS as a clinically useful tool should continue to grow over the next few years.

Coronary angiography has many limitations for the assessment of coronary artery disease. Intracoronary ultrasound imaging may overcome some of these limitations by providing direct visualization of the luminal area. This report describes a case where intracoronary ultrasound imaging was useful for correct assessment of left main coronary artery disease which enabled avoidance of coronary artery bypass grafting in this patient. Intravascular ultrasound may be a good complement to coronary angiography in selected cases of left main coronary artery lesion.

Diastolic dysfunction is a syndrome characterized by impaired ventricular filling. Abnormalities in diastolic function can generally be classified as being the result of abnormal relaxation or of abnormal compliance. Diastolic dysfunction is frequently present in patients with heart failure and it is occasionally the dominant or sole cause of symptoms. It is frequently the result of the convergence of factors such as advanced age, renal dysfunction, left ventricular hypertrophy and impaired coronary perfusion. A good history and physical examination are essential for the diagnosis of diastolic dysfunction. Because it uniquely allows for the noninvasive evaluation of mitral and pulmonary venous flow and provides critical information on the cause of diastolic dysfunction and on associated abnormalities, two-dimensional and Doppler echocardiography is the most useful tool in the comprehensive assessment of diastolic function. Treatment of diastolic dysfunction is difficult and should not only focus on controlling symptoms but also include attempts at resolving the underlying cause. Relief of myocardial ischemia, control of arterial hypertension and regression of ventricular hypertrophy are important objectives of treatment.

Transesophageal echocardiography (TEE) is one of the most significant developments in cardiology and cardiac imaging in the last decade. While monoplane TEE clearly showed the advantages of imaging from the esophagus, biplane TEE was the next important step forward. The combination of transverse and longitudinal axis images served to provide incremental information about various cardiac pathologies. Multiplane TEE is a further advancement that allows continuous visualization of cardiac anatomy by electronic or manual steering of the ultrasound beam through 180 degrees. The intermediate views obtained by beam steering provides an unlimited perspective of normal and abnormal cardiac anatomy. This ability to view cardiac structures in multiple planes aids the understanding of the spatial arrangement of normal cardiac structures and complex disorders of cardiac anatomy. Multiplane TEE technology also eases the examination by reducing the need for probe manipulation. The ability to obtain multiplane images in a sequential manner lays the foundation for three-dimensional imaging of the heart. Ongoing developments in transducer technology should further strengthen the clinical role of TEE.