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Background: The antioxidant probucol reduced coronary restenosis in the MultiVitamins and Probucol (MVP) trial by improving vascular remodelling. Whether calcification limits the extent of adaptive vessel enlargement is not known., Objective: To determine whether plaque composition at the dilated site affects probucol-induced vascular remodelling after angioplasty., Patients and Methods: Beginning 30 days before percutaneous transluminal coronary angioplasty (PTCA), 317 patients received either probucol, vitamins, probucol and vitamins, or placebo. Patients were then treated for six months after PTCA. Intravascular ultrasound (IVUS) was performed post-PTCA and at follow-up in 94 patients (111 segments). The cross-section for serial analysis was the one at the angioplasty site with the smallest lumen area at follow-up. Quantitative analysis consisted of measurements of lumen area and external elastic membrane (EEM) area. The selected cross-section was also divided into five regions according to the type of plaque present (calcific, fibrotic, hypoechoic, fibrohypoechoic or normal). Plaque characterization scores (PCS) (PCS for arc, area, inner perimeter and outer perimeter) were calculated using weighting factors., Results: There were no interactions between potential PCS covariates and probucol main effect on changes in lumenal, EEM and wall area. There were no significant PCS covariates in the model for change in EEM as they were all removed using a backward stepwise procedure. The last potential covariate (area PCS) had a significance level of P=0.48. In contrast, probucol significantly influenced the change in EEM over time (P=0.003)., Conclusion: Plaque composition at the dilated site does not appear to influence probucol-induced vascular remodelling after angioplasty.

The aim of this review is to give an overview of the field of restenosis prevention with antioxidants, put in the perspective of their potential use for the prevention of atherosclerosis progression. Compelling evidence points to oxidative stress as an important trigger in the complex chain of events leading to atherosclerosis. There is also evidence that oxidative stress occurs early after angioplasty. Reactive oxygen species (ROS) can induce endothelial dysfunction and macrophage activation, resulting in the release of cytokines and growth factors that stimulate matrix remodeling and smooth muscle cell proliferation. The accumulation of new extracellular matrix and smooth muscle cells will result in the neointimal formation responsible for lumen narrowing after stent deployment and which contributes to that after balloon angioplasty. In addition, oxidation processes are involved in the cross-linking of collagen fibers, and this coupled with smooth muscle cell contraction and endothelial dysfunction may result in long-term vascular constriction or lack of adaptive vascular remodeling after balloon angioplasty. The powerful antioxidant probucol has been shown to prevent coronary restenosis after balloon angioplasty in the Multivitamins and Probucol (MVP) trial and other clinical studies. However, prolongation of the QT interval with probucol remains a long-term safety concern. AGI-1067, a metabolically stable analog of probucol, is a vascular protectant with strong antioxidant properties as potent to those of probucol. There has been no evidence of prolongation of the QT interval with AGI-1067 in initial clinical studies. The anti-restenosis properties of AGI-1067 are being assessed in the Canadian Antioxidant Restenosis Trial (CART)-1. Considering that oxidative stress and inflammation may persist for a prolonged period after stent placement, treatment with AGI-1067 for the entire period of risk after percutaneous coronary intervention (PCI) [instead of only 4 weeks in CART-1] may result in enhanced protection against luminal renarrowing. This hypothesis will be tested in the randomized, multicenter CART-2 trial. AGI-1067 has been effective at preventing atherosclerosis in all tested animal models, including the low density lipoprotein receptor-deficient and apo-E knockout mice. This has potentially important implications, as PCI and local approaches to prevent restenosis such as coated stents are not expected to prevent atherosclerosis progression, myocardial infarction and cardiovascular death. As the ultimate goal of therapy for patients with coronary artery disease must remain prevention of disease progression and atherosclerosis-related events, CART-2 will test the value of AGI-1067 for the reduction of both post-PCI restenosis and atherosclerosis progression.

Pulse pressure, an indirect measure of vascular stiffness and pulsatile load, predicts clinical events in congestive heart failure (CHF), suggesting that abnormal pulsatile load may contribute to CHF. This study was designed to assess more direct measures of central pulsatile load in CHF. Noninvasive hemodynamic evaluations were performed in 28 subjects with CHF and 40 controls using calibrated tonometry of the brachial, radial, femoral, and carotid arteries along with echocardiographic assessment of left ventricular outflow tract (LVOT) diameter and Doppler flow. Characteristic impedance (Z(c)) was calculated as the ratio of DeltaP (carotid) and DeltaQ (LVOT flow) in early systole. Carotid-radial (CR-PWV) and carotid-femoral (CF-PWV) pulse wave velocities were calculated from tonometry. Augmentation index was assessed from the carotid waveform. Total arterial compliance (TAC) was calculated using the area method. Brachial pulse pressure was elevated (62+/-16 versus 53+/-15 mm Hg, P=0.015) in CHF because of lower diastolic pressure (66+/-10 versus 73+/-9 mm Hg, P=0.003). CHF had higher Z(c) (225+/-76 versus 184+/-66 dyne. sec. cm(-5), P=0.020). CF-PWV did not differ (9.7+/-2.7 versus 9.2+/-2.0, P=0.337), whereas CR-PWV was lower in CHF (8.6+/-1.4 versus 9.4+/-1.5, P=0.038). There was no difference in TAC (1.4+/-0.5 versus 1.4+/-0.6 mL/mmHg, P=0.685), and augmentation index was lower in CHF (8+/-17 versus 21+/-13%, P=0.001). CHF subjects have elevated central pulsatile load (Z(c)), which is not apparent in global measures such as augmentation index or TAC, possibly because of contrasting changes in central and peripheral conduit vessels. This increased pulsatile load represents an important therapeutic target in CHF.

Objectives: Atrial tachycardia-induced remodeling (ATR) and ventricular tachypacing-induced heart failure (HF) create experimental substrates for atrial fibrillation (AF), and both have been reported to produce atrial dilation and hypocontractility. The relative importance of changes in atrial size and contractility in the two models is unknown. This study compared changes in atrial dimensions and emptying in ATR versus HF dog models and related them to AF promotion., Methods: In ATR dogs (n=11), the right atrium (RA) was paced at 400/min for 42 days. In HF dogs (n=10), the right ventricle was paced at 240 bpm for 2 weeks, followed by 3 weeks at 220 bpm. Transthoracic echocardiography was performed at baseline and weekly thereafter. At a terminal electrophysiological study, RA effective refractory period (ERP) was recorded and AF induced repeatedly by atrial burst pacing to measure mean AF duration (DAF)., Results: Left atrial (LA) systolic area increased by 10.0% in ATR versus 48.2% in HF dogs (P=0.008), with significant time-dependent changes in HF (P=0.0001), but not ATR (P=0.16). LA diastolic area increased over time in both groups (P=0.004, 0.0001 for ATR and HF respectively), but increases were much larger in CHF (80.2%) compared to ATR (24.2%, P=0.0002). Similar findings were obtained for RA. Fractional area shortening (FAS) decreased by 19.4% (ATR) versus 41.8% (HF, P=0.007) in LA and 13.7% (ATR) versus 33.7% (HF, P=0.03) in RA. RA ERP correlated with DAF in ATR dogs (r=-0.79, P<0.001), but not in HF dogs (r=0.20, P=NS). DAF and diastolic areas of RA and LA were highly correlated (r=0.71, 0.77; P<0.01 for each) in HF dogs, but not in ATR dogs (r=-0.18, 0.29; P=NS)., Conclusions: Remodeling of atrial size and emptying function is much greater in HF than in ATR. Whereas in ATR, electrophysiological remodeling is of prime importance in AF promotion, structural remodeling (as reflected in changes in atrial size and contraction) appears much more important in HF-induced AF.

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.

Modern pacemakers offer many programming options regarding the AV interval including the ability to vary AV intervals depending on whether atrial activity is paced or spontaneous and to shorten AV intervals with increasing rates. To determine if optimization of these features improves exercise tolerance, 14 patients with intact sinus node function and AV block treated with dual chamber pacemakers were enrolled in a randomized double-blind crossover trial. Doppler echocardiographic measurements of cardiac index and mitral flow were assessed over a range of programmable AV intervals at rest to determine each patient's optimal AV interval. Eleven patients completed serial graded exercise tests with spiroergometry after randomly programming the AV interval three ways in a crossover manner: fixed AV interval = 150 ms without rate adaptation (150/Fixed), fixed AVinterval = 150 ms with rate adaptation (150/R), or optimized AV interval with rate adaptive AV interval shortening (optimized/R). Exercise capacity was determined by maximum oxygen uptake. Ten men and four women, age 64 +/- 8 years, were enrolled. At rest, optimization of the AVintervalimproved the cardiac index by 21% (P < 0.001) and mitral flow by 13.4% (P < 0.001) when compared to least-favorable AV intervals. During exercise, no differences in maximum heart rates were noted. Maximum oxygen uptake was increased in both groups with rate adaptive AVinterval shortening when compared tofixed AVinterval without rate adaptation: 13.9% (adjusted P < 0.04) and 14.6% (adjusted P < 0.02) in optimized/R and 150/R, respectively. No differences were noted between optimized/R and 150/R. In conclusion, rate adaptive AV interval shortening improved exercise tolerance independent of changes in heart rate. However, optimization of the AV interval with Doppler echocardiography at rest did not further improve exercise capacity.

Background: Measurements of pulmonary pressure and resistance are still considered to be the "gold standard" in the evaluation of pulmonary hypertension (PH), despite their limitations in predicting irreversible disease. Hemodynamic assessment also only provides a global evaluation of the pulmonary vascular bed, whereas PH is an inhomogeneous disease of the vessel wall., Methods and Results: We assessed the value of intravascular ultrasound (IVUS) in 30 patients with suspected PH and correlated the structural changes in distal pulmonary arteries found on IVUS with conventional hemodynamic data. Plasma endothelin (ET)-1 levels and pulmonary ET-1 extraction also were measured as markers of the severity of PH. The anatomic abnormalities revealed by IVUS were more severe in the lower lobes than in the upper lobes, as evidenced by the greater percentage of wall thickness (WT), the smaller lumen diameter/WT and lumen area/total vessel area (p < 0.05 for each). IVUS anatomic indexes correlated directly with hemodynamic data (eg, with pulmonary arterial systolic pressure; r = 0.56; p < 0.001) and ET-1 levels but inversely with pulmonary ET-1 extraction., Conclusion: Patients with PH have greater pulmonary arterial WT that is more severe in the lower lobes than in the upper lobes. The severity of structural abnormalities found on IVUS is directly correlated with hemodynamic findings and ET-1 levels. IVUS may provide useful additional information in the assessment of patients with PH.

Using transgenesis as a paradigm, we show here that alpha1-adrenergic receptors (alpha1AR) play an important role in cardiac homeostasis. Cardiomyocyte-specific overexpression of the alpha(1B)AR subtype resulted in the development of dilated cardiomyopathy and death at ~9 mo of age with typical signs of heart failure. Histological analyses showed the enlargement of all four cardiac chambers and cardiomyocyte disarray in the failing hearts. Transgenic animals showed increased left ventricular areas, as assessed by echocardiography. In addition, a progressive decrease in left ventricular systolic function was revealed. The abundance and activity of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) were reduced, and the ratio of phospholamban to SERCA2 was increased. alpha-Myosin heavy chain (MHC) mRNA was less abundant in older transgenic ventricles, whereas beta-MHC was induced in the failing hearts. Titin mRNA abundance was decreased at 9 mo, whereas atrial natriuretic factor mRNA was elevated at all times. This model mimics structural and functional features of idiopathic dilated cardiomyopathy. The results of this study suggest that chronic alpha1AR activity is deleterious for cardiac function.

Introduction: Recent animal studies demonstrated the feasibility and safety of applying percutaneous catheter cryoablation technology for ablation of arrhythmogenic sites. The studies also showed that reversible "ice mapping" can be performed before creating permanent lesions. We investigated the feasibility and safety of applying this new technology in man., Methods and Results: Cryoablation of the AV node (AVN) using a 9-French quadripolar catheter with a 4-mm electrode tip was attempted in 12 patients (mean age 67.8 +/- 11.4 years) with refractory atrial fibrillation. Whereas technical issues prevented adequate tissue contact in two patients, complete AVN block was obtained in the remaining 10 patients after 4.8 +/- 1.9 cryoapplications lasting 5.5 +/- 0.2 minutes resulting in temperatures of -58.1 degrees +/- 5.4 degrees C. In all patients with sinus rhythm at the time of the procedure, cryomapping at warmer temperatures induced reversible AVN block and allowed confirmation of a successful site before definitive ablation. Intracardiac echocardiography was performed in three patients and allowed visualization of the cryocatheter-endocardial contact and cryolesion formation. No major procedural complications were reported. After 6 months of follow-up, 8 of 10 initially successful patients remained in complete block; 1 had partial recovery of AVN conduction manifested by atrial fibrillation with a slow ventricular response, and 1 fully recovered AVN conduction., Conclusion: (1) Catheter cryoablation of the AVN can be performed safely in man. (2) Reversible cryomapping is feasible and may offer an advantage over radiofrequency ablation. (3) Cryocatheter-endocardial contact and cryolesion growth can be monitored with intracardiac echocardiography.

Background: 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., Objective: To determine the morphological predictors of restenosis in patients treated with probucol., Patients and Methods: 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., Results: 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., Conclusions: 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.

Background: 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., Methods: 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., Results: Both systems correlated well for areas (r > or = 0.90, p < 0.0001) and diameters (r > or = 0.84. p < 0.0001) 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, p < 0.055) and diameter (-0.08 and 0.16 mm, p < 0.0001). 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 (r > or = 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., Conclusions: 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.

Echocardiography is the modality of choice for the noninvasive recognition of vegetations and abscesses that complicate endocarditis. Vegetation size is highly variable, and it has been suggested that large vegetations are related to a more complicated course. The case we present is unusual in that the echocardiographically detected vegetation was very large, highly mobile, and caused severe obstruction of the left ventricular outflow tract, which led to impaction and cardiac arrest.

Objectives: The aim of this study was to determine the natural history of postangioplasty intravascular ultrasound (IVUS)-detected dissections and to assess the influence of intracoronary beta-radiation on dissection resolution., Background: Intracoronary radiotherapy is considered to impair exaggerated vessel healing. Conversely, excessive healing impairment may increase the risk of complications due to unhealed dissection. Alternatively, residual dissection may represent an innocent marker of adequate therapy., Methods: Immediate postangioplasty and six-month follow-up IVUS studies of 94 patients in the IVUS substudy of the MultiVitamins and Probucol (MVP) trial and 26 nonstented patients in the Beta Energy Restenosis Trial (BERT) were analyzed for the presence or absence of dissection., Results: Of the 28 patients with postangioplasty dissections in MVP, only one had evidence of residual dissection at six months (95% confidence interval [CI] for failure rate 0.2%; 20.2%). Conversely, 9 of 16 dissections had healed in BERT (95% CI for failure rate 30.6%; 79.2%) (p < 0.0002). Nevertheless, an index based on dissection arc and length demonstrated improvement in the irradiated patients. Irradiated patients with residual dissections showed significant increase in lumen area at six-months (5.10 +/- 0.98 to 7.11 +/- 2.61 mm2, p < 0.02) not noted when there was resolution of the dissection (6.03 +/- 2.38 to 6.36 +/- 3.33 mm2, p = NS). In both groups the external elastic membrane area was unchanged at follow-up., Conclusions: Resolution appears to be the natural history of IVUS-detected dissections in most cases. Significant resolution of dissection occurs following intracoronary beta-radiation as reflected in reduced dissection index at six-months in these patients, although significant impairment of vessel wall healing was noted.

Compelling evidence points to oxidative stress as an important trigger in the complex chain of events leading to atherosclerosis. Randomized clinical trials have not provided definitive evidence of the beneficial effect of antioxidant vitamins. Problems associated with the use of vitamins include their potential pro-oxidant effects and the decreased absorption of natural gamma-tocopherol caused by alpha-tocopherol supplements. Probucol and amlodipine are more powerful lipophilic antioxidants than vitamin E. They also do not appear to have significant pro-oxidant properties. Probucol has been shown to prevent coronary restenosis after balloon angioplasty in clinical trials. Its high density lipoprotein-lowering effect, however, prevents it from being protective against progression of coronary atherosclerosis. Slowing or reversing the atherosclerotic process with an antioxidant likely requires the use of a powerful lipophilic antioxidant that has neutral or positive effects on serum lipids when given alone or in combination with a lipid-lowering agent.

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.

Background: The treatment of unstable angina targets the specific pathophysiological thrombotic process at the site of the active culprit lesion. In unstable angina due to a restenotic lesion, smooth muscle cell proliferation and increased vasoreactivity may play a more important role than thrombus formation. Therefore, the relative benefits of nitroglycerin and heparin might differ in unstable angina associated with restenosis compared with classic unstable angina., Methods and Results: We randomized 200 patients hospitalized for unstable angina within 6 months after angioplasty (excluding those with intracoronary stents) to double-blind administration of intravenous nitroglycerin, heparin, their combination, or placebo for 63+/-30 hours. Recurrent angina occurred in 75% of patients in the placebo and heparin-alone groups, compared with 42.6% of patients in the nitroglycerin-alone group and 41.7% of patients in the nitroglycerin-plus-heparin group (P<0.003). Refractory angina requiring angiography occurred in 22.9%, 29.2%, 4. 3%, and 4.2% of patients, respectively (P<0.002). The odds ratios for being event free were 0.24 (95% CI, -0.13 to 0.45, P=0.0001) for nitroglycerin versus no nitroglycerin and 0.98 (95% CI, -0.55 to 1. 73, P=NS) for heparin versus no heparin. No patient died or suffered myocardial infarction., Conclusions: Intravenous nitroglycerin is highly effective in preventing adverse ischemic events (recurrent or refractory angina) in patients with unstable angina secondary to restenosis, whereas heparin has no effect.

Objective: To determine whether patients with cardiac tamponade are subject to delays and clinical deterioration before undergoing echocardiography and pericardial drainage., Design: Retrospective study., Setting: The Montreal Heart Institute, Montreal, Quebec, a cardiology referral centre., Patients: 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., Results: 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., Conclusion: 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.

This study compared the rapidity of onset, the magnitude, and the duration of action of 2 short-acting nitroglycerin preparations using high-resolution brachial ultrasound. Both sublingual tablet and lingual spray formulations caused maximal vasodilation at 3 minutes; however, the spray provided faster (at 2 minutes), greater, and more prolonged (15 minutes) vasodilation than the tablet.

While radiofrequency catheter ablation is very effective, it does not allow for prediction of success prior to full delivery of the energy. We investigated the use of cryoablation using a new catheter on the AV node to determine (1) if a successful site might be identified prior to the ablation itself, and (2) the parameters of cryoablation of the AV node using a new cryocatheter. In eight dogs, the cryoablation catheter was advanced to the AV node to produce transient high degree AV block by lowering the temperature to a minimum of -40 degrees C (ice mapping). Transient high degree AV node block was obtained in seven of eight animals at a mean temperature of -39.9 +/- 11.6 degrees C. No significant pathological modification was found in all animals but one and, in all cases, electrophysiological parameters of the AV node measured before, 20 minutes, 60 minutes, and up to 56 days after cryoapplication were not significantly different. In the 12 other dogs, after ice mapping, cryoablation of the AV node was attempted with a single freeze-thaw cycle in 6 dogs (group I) and a double freeze-thaw cycle in the other 6 dogs (group II). Chronic complete AV block was obtained in only one animal in group I compared to all animals in group II. Ablation of the AV node is effective with a double freeze-thaw cycle using a percutaneous catheter cryoablation system. Ice mapping of the area allows for identification of the targeted site.

Exercise treadmill testing (ETT) is considered an unreliable method for detection of restenosis after percutaneous transluminal coronary angioplasty (PTCA). The studies on which this belief is based have used quantitative coronary angiography (QCA) as a reference. The inherent limitations of angiography have been demonstrated by intravascular ultrasound (IVUS). To determine the value of ETT for detecting restenosis when IVUS criteria are used to define restenosis, we studied 29 patients with angiographically documented 1-vessel coronary disease (<35% stenosis in all nondilated segments) who underwent angioplasty. ETT was performed < or =2 weeks before follow-up angiography and IVUS imaging. Only patients without any abnormalities precluding an accurate reading of the ST segment during ETT were included. Restenosis was defined as a > or =50% diameter stenosis by QCA criteria and as a cross-sectional area narrowing of > or =75% by IVUS. The ETT was positive in 12 patients and restenosis was documented by QCA and IVUS in 38% and 48% of cases, respectively. Sensitivity, specificity, and positive and negative predictive values of ETT when QCA was used as a reference were 55%, 67%, 50%, and 71%, respectively. This corresponded to an accuracy of 62% when compared with QCA. Sensitivity, specificity, and positive and negative predictive values were 79%, 93%, 92%, and 82% when ETT was compared with IVUS, with an accuracy of 86% (p = 0.002). Thus, ETT is a reliable noninvasive method for detecting the presence of restenosis after PTCA in patients with 1-vessel coronary artery disease. The presence of > or =75% cross-sectional narrowing shown by IVUS is well correlated with > or =1-mm ST-segment depression at follow-up ETT after PTCA.

Background: Cholesterol lowering reduces coronary events. One mechanism could be improvement of endothelial function. In line with this hypothesis, this study investigates whether cholesterol reduction can result in rapid improvement of endothelial function after acute coronary syndromes., Methods and Results: Patients with acute myocardial infarction or unstable angina and total cholesterol levels at admission >/=5.2 mmol/L or LDL >/=3.4 mmol/L were randomized to placebo (n=30) or pravastatin 40 mg daily (n=30) for 6 weeks. Brachial ultrasound was used to measure endothelium-dependent flow-mediated dilatation (FMD) and response to endothelium-independent nitroglycerin. Changes in the levels of markers of platelet activation, coagulation factors, and plasma endothelin levels were also assessed. Total and LDL cholesterol levels were similar at admission and before randomization in both groups. With pravastatin, but not with placebo, they decreased by 23% (P<0.05) and 33% (P<0.01), respectively. FMD was unchanged with placebo, 5.43+/-0.74% (mean+/-SEM) to 5.84+/-0.81%, but increased with pravastatin, 4.93+/-0.81% to 7.0+/-0.79% (P=0.02), representing a 42% relative increase. Responses to nitroglycerin were similar during the time course of the study in the 2 groups. Markers of platelet activity, coagulation factors, and endothelin levels were not affected by pravastatin., Conclusions: Cholesterol reduction with pravastatin initiated early after acute coronary syndromes rapidly improves endothelial function after 6 weeks of therapy.

Background: Limitations of the dog model of orthotopic heart transplantation to study rejection include the need for extracorporeal circulation and transfusions. Heterotopic cervical heart transplantation may improve on these limitations. It is not known whether the natural history after heterotopic transplant is similar to that after orthotopic grafting., Methods: Twenty-one dogs underwent cervical heterotopic heart transplantation. Serial echocardiographic studies were performed 1 to 3 hours after surgery, at 24 hours, 48 hours later, and immediately before killing (5 to 7 days)., Results: LV diastolic and systolic areas were elevated immediately after transplantation (4.95+/- 1.49 cm2 and 3.36+/-1.18 cm2 respectively) but decreased at 24 hours (3.93+/-1.20 cm2, p = 0.0003 and 2.44+/-0.96 cm2, p = 0.16). Thereafter, a progressive increase in LV diastolic and systolic areas was observed until sacrifice (5.53+/-2.20 cm2 and 4.59 +/-2.14 cm2, p < 0.001 vs 24 hours). LV fractional area shortening (FAS) and fractional volume change were depressed immediately after transplantation (28.2+/- 12.8% and 40.4+/-12.3%, respectively), but increased at 24 hours (35.7+/-10.0%,p = 0.11 and 50.3+/-4.0%,p = 0.02). FAS decreased at 48 hours to 19.6+/-11.1% (p = 0.01 vs 24 hours). The centractility indexes were markedly reduced before killing (FAS = 14.0+/-8.2% and LVEF = 18.4+/-1.3%, p < 0.0005 vs 24 hours). The thickness of the interventricular septum increased from 11.9+/-2.0 mm at baseline to 14.4+/-4.2 mm before sacrifice (p = 0.007)., Conclusion: The evolution of dogs after heterotopic cervical heart transplant is comparable to that after the more standard orthotopic graft. Considering its multiple practical advantages including the easy echocardiographic follow-up, heterotopic transplantation may become a very practical model to use for the study of rejection after heart transplantation.

We report a case of severe aortic regurgitation occurring immediately after the insertion of a mitral annuloplasty ring. On transesophageal echocardiography, regurgitation was found to originate from the retracted left coronary cusp. On direct examination, part of the aortic wall was folded, but no suture could be identified. It was reasoned that tension created by the ring caused the retraction. The problem was corrected by releasing three sutures on the ring. Postoperative course was uneventful.

Background: Endovascular radiation is emerging as a potential solution for the prevention and treatment of restenosis. Its effects on the morphology of unstented vessels cannot be determined by angiography and therefore require the use of intravascular ultrasound., Methods and Results: Through a 5F noncentered catheter for delivery of a 90Sr/Y source train, 12, 14, or 16 Gy at 2 mm was delivered to native coronary arteries after successful balloon angioplasty in 30 patients. Four patients required stent deployment in the first week. Quantitative coronary angiography and IVUS were performed during the initial procedure and at 6-month follow-up. Binary angiographic restenosis was present in 3 of 30 patients, with target lesion and vessel revascularization performed in 3 and 5 patients, respectively. Angiographic late loss was -0.02+/-0.60 mm, with a -0.09+/-0.46 loss index. IVUS demonstrated no significant reduction in lumen area (from 5.69+/-1.72 mm2 after treatment to 6. 04+/-2.63 mm2 at follow-up), with no significant change in external elastic membrane area (13.71+/-4.54 to 14.22+/-4.71 mm2) over the 6-month follow-up. Wall area was 8.01+/-3.85 mm2 after radiation therapy and 8.19+/-3.44 mm2 at follow-up (P=NS). No significant differences were noted between the different dose groups., Conclusions: beta-Radiation therapy resulted in a low restenosis rate with negligible late loss by angiography. By IVUS, beta-radiation was shown to inhibit neointima formation, with no reduction of total vessel area at 6-month follow-up.

Background: 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)., Methods and Results: 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)., Conclusions: 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.

The purpose of this study was to explore the potential of intracardiac echocardiography in monitoring lesion formation and assisting with the assessment of ablative lesions using microwave energy. Microwave energy is a promising modality for catheter ablation. Because microwave lesions may have considerable variability in dimension, the ability to assess them may be particularly useful. One hundred twenty-five microwave lesions were created in vitro in ovine left ventricles. Correct assessment of catheter-endocardial contact was possible in virtually all cases. Intracardiac imaging always identified correctly whether or not an ablation was performed. During ablation, gas formation was observed in all instances. Sensitivity, specificity, and predictive values for identification of ablation lesions were 88% to 92%. Although the correlations with pathology for lesion dimensions were relatively poor, intracardiac imaging had a predictive accuracy of 80% to 85% to discriminate small from large lesions. Intracardiac guidance for microwave ablation is useful for verifying tissue-electrode contact, monitoring lesion formation, and localizing lesions. It is also a useful tool for the assessment of lesion size. These attributes, combined with the ability to facilitate transseptal catheterization and to identify complications such as hemopericardium, make intracardiac echocardiography a potentially useful method for guiding microwave ablation of arrhythmic foci.

Background: Endothelium-dependent vasodilation is impaired in asymptomatic subjects with risk factors for atherosclerosis., Purpose: To determine whether a three-month integrative primary prevention program can improve endothelial function in asymptomatic subjects with risk factors for atherosclerosis., Patients and Methods: 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)., Results: After three months, peak oxygen uptake increased significantly from 25.4 +/- 4.9 to 27.5 +/- 4.8 mL/kg/min (P < 0.005), and LDL level decreased significantly from 4.48 +/- 0.92 to 4.00 +/- 0.83 mmol/L (P < 0.005). 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)., Conclusions: 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.

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.

Stent implantation represents a major step forward since the introduction of coronary angioplasty. As indications continue to expand, better understanding of the early and late biocompatibility issues appears critical. Persisting challenges to the use of intracoronary stents include the prevention of early thrombus formation and late neointima development. Different metals and designs have been evaluated in animal models and subsequently in patients. Polymer coatings have been proposed to improve the biocompatibility of metallic stents or to serve as matrix for drug delivery and they are currently undergoing clinical studies. The promises of a biodegradable stent have not yet been fulfilled although encouraging results have recently been reported. Continuous low dose-rate brachytherapy combining the scaffolding effect of the stent with localized radiation therapy has witnessed the development and early clinical testing of radioactive stents. The combined efforts of basic scientists and clinicians will undoubtedly contribute to the improvement of stent biocompatibility in the future.

Retrograde cardioplegia is relatively safe, with a rate of coronary sinus rupture of 0.6%. With the advent of perioperative transesophageal echocardiography, it is now possible to detect and evaluate the extent of damage consequent to the use of retrograde cardioplegia and better formulate an intraoperative course of action. The evolution of these lesions can also be monitored by transesophageal echocardiography during the postoperative period.

We report the case of a coronary aneurysm observed 6 mo after cutting balloon angioplasty complicated by a mild perforation. Intravascular ultrasound allowed characterization of the malformation as a true aneurysm. The clinical course was uneventful.

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.

Objective: Pulmonary hypertension (PHT) is associated with increased endothelin-1 (ET-1) levels that correlate with the severity of the disease. The pulmonary circulation is an important site for ET-1 metabolism and may modulate plasma ET-1 through an increase in production, a reduction in removal, or a combination of both. We measured and compared pulmonary metabolism of circulating ET-1 in controls and in patients with PHT., Methods and Results: The indicator-dilution technique was combined with measurements of ET-1 levels to quantify pulmonary metabolism of ET-1 in controls (n = 13) and in patients with PHT (n = 17). ET-1 levels doubled in PHT (p < 0.05) and, although there was no difference between aortic and pulmonary artery levels in controls (0.68+/-0.09 and 0.61+/-0.08 pg/ml, respectively, p = 0.22), they tended to be higher in PHT (1.23+/-0.26 vs 1.07+/-0.19 pg/ml, p = 0.08). Pulmonary extraction of tracer iodine-125-ET-1 was reduced from 47%+/-2.0% in the controls to 34%+/-3.6% in PHT (p = 0.005) and inversely correlated with the severity of pulmonary hypertension (r = -0.524, p = 0.03). Consequently, circulating ET-1 clearance was reduced by PHT from 1424+/-77 ml/min to 892+/-119 ml/min (p < 0.001). Pulmonary production of circulating ET-1 (in picograms per minute) was not different but the quantity of ET-1 that survives passage through the lungs was increased by PHT (1860+/-359 pg/min vs 992+/-152 pg/min, p = 0.037)., Conclusion: PHT is associated with a reduced pulmonary clearance of ET-1 that contributes to the increase in circulating levels.

Background: Restenosis remains the major limitation of coronary angioplasty. Coronary stents have reduced the incidence of restenosis in selected patients with relatively large vessels. No strategies to date have demonstrated a beneficial effect in vessels < 3.0 mm in diameter. We have shown in the MultiVitamins and Probucol (MVP) Trial that probucol, a potent antioxidant, reduces restenosis after balloon angioplasty. The purpose of this study was to determine whether the benefit of probucol therapy is maintained in the subgroup of patients with smaller coronary vessels., Methods and Results: We studied a subgroup of 189 patients included in the MVP trial who underwent successful balloon angioplasty of at least one coronary segment with a reference diameter < 3.0 mm. One month before angioplasty, patients were randomly assigned to one of four treatments: placebo, probucol (500 mg), multivitamins (beta-carotene 30000 IU, vitamin C 500 mg, and vitamin E 700 IU), or probucol plus multivitamins twice daily. The treatment was maintained until follow-up angiography was performed at 6 months. The mean reference diameter of this study population was 2.49+/-0.34 mm. Lumen loss was 0.12+/-0.34 mm for probucol, 0.25+/-0.43 mm for the combined treatment, 0.35+/-0.56 mm for vitamins, and 0.38+/-0.51 mm for placebo (P=.005 for probucol). Restenosis rates per segment were 20.0% for probucol, 28.6% for the combined treatment, 45.1% for vitamins, and 37.3% for placebo (P=.006 for probucol)., Conclusions: Probucol reduces lumen loss and restenosis rate after balloon angioplasty in small coronary arteries.

Background: 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., Methods: 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., Results: 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)., Conclusions: The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

Resistant coronary lesions remain a challenge for modern angioplasty. Classical approaches include high-pressure inflations, prolonged inflations, or balloon oversizing. More recently, new technologies like rotablator, atherectomy, or laser have been proposed as adjunct to balloon angioplasty for the treatment of these specific lesions. However, all these technologies remain more difficult to handle, costly, and they do not offer long-term benefit over conventional methods. Therefore, a simple device such as the cutting balloon catheter which has been developed from a standard over the wire balloon catheter, may prove to be useful in resistant coronary lesions. We present our single center experience using the new cutting balloon catheter in six resistant lesions.

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.

Objectives: 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., Background: 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., Methods: 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., Results: 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 (p < 0.005). 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)., Conclusions: 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.

Mechanical prostheses induce artifacts that decrease the accuracy of conventional transthoracic echocardiographic imaging for the detection and quantitation of periprosthetic mitral regurgitation. In 15 patients undergoing transthoracic echocardiography, injection of sonicated albumin significantly enhanced the assessment of periprosthetic mitral regurgitation with an accuracy similar to that of transesophageal echocardiography.

The mean dP/dt during isovolumetric contraction (mean dP/dt(ic)) is a new echocardiographic index of ventricular function that has been shown to approximate and closely correlate with invasively measured peak dP/dt. It is amenable to rapid measurement via transesophageal echocardiography (TEE) and is theoretically independent of variations in ventricular anatomy and wall motion. It is therefore well suited for the assessment of ventricular function during surgery. The purpose of this study was to assess the clinical value of TEE determinations of mean dP/dt(ic) before and after cardiopulmonary bypass (CPB). The mean dP/dt(ic) of 50 patients undergoing open heart surgery for a variety of congenital and acquired heart defects was measured before and 15-30 minutes after CPB. Mean dP/dt(ic) averaged 1147 +/- 492 before and 1428 +/- 702 mmHg/sec after CPB (P < 0.01). Mean dP/dt(ic) was unchanged or increased in 45 patients and fell in only 5 patients. It increased significantly even among patients who did not receive supplemental inotropic agents. Mean dP/dt(ic) correlated well with the shortening fraction, especially among patients without segmental left ventricular wall-motion abnormalities. The general patterns observed for mean dP/dt(ic) were also seen when the data was corrected for variations in heart rate. A preoperative mean dP/dt(ic) < 765 mmHg/sec or a heart rate corrected mean dP/dt(ic) < 620 mmHg/sec indicated a high likelihood that inotropic support would be needed to facilitate weaning from CPB. Mean dP/dt(ic) may be a clinically useful, quantitative TEE index of perioperative changes in ventricular contractility.

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.

Angiosarcoma of the heart is a rare tumor. This tumor is most frequently located in the right atrium and pericardium. Localization of a tumor in the interatrial septum usually suggests atrial myxoma. We report two cases of angiosarcoma originating from the interatrial septum, one extending into the right atrium and the other into the left atrium, mimicking atrial myxomas. Transesophageal echocardiography allowed the diagnosis and comprehensive assessment of compromised structures.

Assessment of cardiac diseases commonly involves the use of spectral Doppler echocardiography. Its use, however, often requires manual digitization of various transvalvular flow profiles. A new approach has been developed for on-line analysis of Doppler data, which involves thresholding based on the signal/noise ratio, calculating instantaneous values, and plotting on the spectral display in real time. We examined the reliability of this new method in 32 patients with 59 various flow jets by comparing it with the data derived by manual analysis. Correlations between the algorithm analysis and manual analysis for peak velocity, peak gradient, velocity-time integral, and acceleration time were excellent. These indexes were obtained with the algorithm in a shorter time and with better reproducibility than with manual analysis. Thus this new adaptive Doppler analysis algorithm yields reliable on-line quantification of valuable hemodynamic variables and represents an advance in quantitative echocardiography.

Aneurysm of the membranous portion of the ventricular septum and accessory valvular tissue are two infrequent congenital lesions. This case illustrates a rare association of aneurysm of the membranous septum and accessory valvular tissue originating from the mitral valve, causing right-sided ventricular outflow tract obstruction in a patient with corrected transposition. Multiplane transesophageal echocardiography allowed for determination of the dual nature of the obstruction.