S.G. Carlier

Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience.

OBJECTIVES In this study, we assess the value of sirolimus eluting stent (SES) implantation in patients with complex in-stent restenosis (ISR). BACKGROUND The treatment of ISR remains a therapeutic challenge, since many pharmacological and mechanical approaches have shown disappointing results. The SESs have been reported to be effective in de-novo coronary lesions. METHODS Sixteen patients with severe, recurrent ISR in a native coronary artery (average lesion length 18.4 mm) and objective evidence of ischemia were included. They received one or more 18 mm Bx VELOCITY SESs (Cordis Waterloo, Belgium). Quantitative angiographic and three-dimensional intravascular ultrasound (IVUS) follow-up was performed at four months, and clinical follow-up at nine months. RESULTS The SES implantation (n = 26) was successful in all 16 patients. Four patients had recurrent restenosis following brachytherapy, and three patients had totally occluded vessels preprocedure. At four months follow-up, one patient had died and three patients had angiographic evidence of restenosis (one in-stent and two in-lesion). In-stent late lumen loss averaged 0.21 mm and the volume obstruction of the stent by IVUS was 1.1%. At nine months clinical follow-up, three patients had experienced four major adverse cardiac events (two deaths and one acute myocardial infarction necessitating repeat target vessel angioplasty). CONCLUSIONS The SES implantation in patients with severe ISR lesions effectively prevents neointima formation and recurrent restenosis at four months angiographic follow-up.

Advancing intravascular ultrasonic palpation toward clinical applications

This paper describes the first reported attempt to develop a real-time intravascular ultrasonic palpation system. We also report on our first experience in the catherization laboratory with this new elastographic imaging technique. The prototype system was based on commercially available intravascular ultrasound (US) scanner that was equipped with a 20-MHz array catheter. Digital beam-formed radiofrequency (RF) echo data (i.e., 12 bits, 100 Hz) was captured at full frame rate from the scanner and transferred to personal computer (PC) memory using a fast data-acquisition system. Composite palpograms were created by applying a one-dimensional (1-D) echo tracking technique in combination with global motion compensation and multiframe averaging to several pairs of RF echo frames that were obtained in the diastolic phase of the cardiac cycle. The quality of palpograms was assessed by conducting experiments on vessel phantoms and on patients. The results demonstrated that robust and consistent palpograms could be generated in almost real-time using the proposed system. Good correlation was observed between low strain values and regions of calcification as identified from the intravascular US (IVUS) sonograms. Although the clinical results are clearly preliminary, it was concluded that the prototype system performed sufficiently well to warrant further and more in-depth clinical investigation.

Novel developments in intravascular imaging

In the development of intravascular ultrasound (IVUS), a serious emphasis has been given to the improvement of the image quality in terms of resolution. The image quality is indeed a very important issue, but there is lot more information hidden in the ultrasound signals than is currently exploited by commercially available IVUS equipment. Over the past few years, at the Thorax centre we have been exploring the possibilities of analysing sequences of radiofrequency (RF) traces. This could provide a significant extension of the functionality of the IVUS machines. It gives possibilities for local elasticity assessment, flow estimation and enhanced lumen detection. This paper is an up to date impression of where RF-data analysis has taken us.

Ultrafiltration improves aortic compliance in haemodialysis patients.

An elevated pulse pressure leads to an increased pulsatile cardiac load, and results from arterial stiffening. The aim of our study was to test whether a reduction in volume overload by ultrafiltration (UF) during haemodialysis (HD) leads to an improvement of aortic compliance. In 18 patients, aortic compliance was estimated noninvasively before and after HD with UF using a pulse pressure method based on the Windkessel model. This technique has not been applied before in a dialysis population, and combines carotid pulse contour analysis by applanation tonometry with aortic outflow measurements by Doppler echocardiography. The median UF volume was 2450 ml (range 1000–4000 ml). The aortic outflow volume after HD (39 ml; 32–53 ml) was lower (P=0.01) than before (46 ml; 29–60 ml). Carotid pulse pressure after HD (42 mmHg; 25–85 mmHg) was lower (P=0.01) than before (46 mmHg; 35–93 mmHg). Carotid augmentation index after HD (22%; 3–30%) was lower (P=0.001) than before (31%; 7–53%). Carotid–femoral pulse wave velocity was not different after HD (8.7 m/s; 5.6–28.9 m/s vs 7.7 m/s; 4.7–36.8 m/s). Aortic compliance after HD (1.10 ml/mmHg; 0.60–2.43 ml/mmHg) was higher (P=0.02) than before (1.05 ml/mmHg; 0.45–1.69 ml/mmHg). The increase in aortic stiffness in HD patients is partly caused by a reversible reduction of aortic compliance due to volume expansion. Volume withdrawal by HD moves the arterial wall characteristics back to a more favourable position on the nonlinear pressure–volume curve, reflected in a concomitant decrease in arterial pressure and improved aortic compliance.

Quantification of plaque volume, shear stress on the endothelium, and mechanical properties of the arterial wall with intravascular ultrasound imaging

Present intravascular echographic imaging (IVUS) is based on either the mechanically rotated single element catheter or the multi-element phased array catheter principle. In both methods the ultrasonic beam is rotated through 360 degrees and the cross-sectional echo image of plaque and wall structures is visualised. A new development based on intravascular ultrasound is calculation of mechanical properties of the arterial wall. In this so-called elastographic approach, high frequency information obtained at identical positions in the arterial wall is compared under systolic and diastolic pressures. Minute shifts in the echo data indicate local compressibility. It thus becomes possible to indicate areas of high or low strain, which correspond to soft and hard material. Three-dimensional information can be obtained if the position of cross sectional slices is recorded with a pull-back device and slices are united into a 3D image. On the basis of such information it has become possible to view stents in 3D, and which interactive software, to calculate automatically plaque volume. With pull-back information only, the artery is reconstructed as a “straight pipe”. Only when the biplane X-ray information is combined with the intravascular pull-back echo information can the true 3D reconstruction of the artery be constructed. Given the true geometric lumen information, it becomes possible, under certain assumptions, to derive the luminal fluid dynamics. From this, shear stress values close to the arterial wall can be evaluated. Under the assumption that low values for local shear stress are areas prone to restenosis, predictions of endangered areas can be made.

Flow estimation using an intravascular imaging catheter

Coronary flow assessment can be useful for determining the hemodynamic severity of a stenosis and to evaluate the outcome of interventional therapy. We developed a method for measuring the transverse flow through the imaging plane of an intravascular ultrasound (IVUS) catheter. This possibility has raised great clinical interest since it permits simultaneous assessment of vessel geometry and function with the same device. Furthermore, it should give more accurate information than combination devices because lumen diameter and velocity are determined at the same location. Flow velocity is estimated based on decorrelation estimation from sequences of radiofrequency (RF) traces acquired at nearly the same position. Signal gating yields a local estimate of the velocity. Integrating the local velocity over the lumen gives the quantitative flow. This principle has been calibrated and tested through computer modeling, in vitro experiments using a flow phantom and in vivo experiments in a porcine animal model, and validated against a Doppler element containing guide wire (Flowire) in humans. Originally the method was developed and tested for a rotating single element device. Currently the method is being developed for an array system. The great advantage of an array over the single element approach would be that the transducer has no intrinsic motion. This intrinsic motion sets a minimal threshold in the detectable velocity components. Although the principle is the same, the method needs some adaptation through the inherent different beamforming of the transducer. In this paper various aspects of the development of IVUS flow are reviewed.

In vivo validation of blood flow estimation using the decorrelation of radiofrequency intravascular echo signals

Last year we reported on a method for flow estimation from the decorrelation properties of radio frequency intravascular ultrasound signals from blood. This year optimization of the method and validation in an animal study and the first human applications are reported. In vivo validation results obtained in various flow conditions indicate that this method is able to provide accurate and reproducible measure of blood volume flow rate, offering a unique opportunity to simultaneously assess physiologic and anatomic parameters in humans.

A comparison of methods for assessing total arterial compliance

There are several methods of assessing total arterial compliance (TAC) based on the two element Windkessel model, which is a ratio of pressure and volume, but the optimal technique is unclear. In this study, three methods of estimating TAC were compared to determine which was the most robust in a large group of patients with and without cardiovascular risk. In all, 320 patients (170 men; age 55±10) were studied; TAC was determined by the pulse-pressure method (PPM), the area method (AM) and the stroke volume/pulse-pressure method (SVPP). We obtained arterial waveforms using radial applanation tonometry, dimensions using two-dimensional echocardiography and flow data by Doppler. Clinical data, risk factors, echo parameters and TAC by all three methods were then compared. TAC (ml mm Hg–1) by the PPM was 1.24±0.51, by the AM 1.84±0.90 and by the SVPP 1.96±0.76 (P<0.0001 between groups). Correlation was good between all methods: PPM/AM r=0.83, PPM/SVPP r=0.94 and AM/SVPP r=0.80 (all P<0.0001). Subgroup analysis showed significant differences between patients with and those without cardiovascular risk for all three methods; TAC–AM and TAC–SVPP values were similar and significantly higher than TAC–PPM. The only significant relationships observed with TAC and echo parameters were in left ventricular (LV) septal thickness (R2=0.07; P<0.0001) and LV mass (R2=0.04; P=0.004). Normal and abnormal values of TAC vary according to method, which should be expressed. Each of the techniques shows good correlation with each other, however, values for TAC–PPM are significantly lower. TAC–PPM and TAC–SVPP are comparable in determining differences between groups with and without cardiovascular risk.

Nigh resolution IVUS elastography in patients

Intravascular ultrasound (IVUS) elastography is a new imaging technique that reveals local mechanical properties of the vascular wall by measuring the local strain. Last year, low resolution elastograms (64 angles) were presented. In this study, we present high resolution elastograms. Patients (n=8) referred for Percutaneous Transluminal Coronary Angioplasty were investigated with an EndoSonics InVision echoapparatus. The beam-formed image mode (512 angles) ultrasound data (Fc=20 MHz) was acquired with an acquisition system that was assembled in collaboration with EndoSonics. Elastograms were determined using data acquired near end-diastole. In this phase of the pressure cycle, catheter motion was minimal. Frames with a pressure difference of approx. 5 mmHg were taken to determine the elastograms. Elastograms of soft, calcified and stented plaques were determined. The elastogram of a soft plaque, as identified from the deformation during the pressure cycle, reveals strain values up to 2% with increased strain regions at the shoulders of the plaque. Calcified material, as identified from the echogram, shows strain values of 0-0.2%. The elastogram of stented plaques reveals very low strain values, except for two regions: these are between the stent struts and at the shoulders of the plaque.

Intracoronary elastography in the catheterisation laboratory: preliminary patient results

Intravascular ultrasound (IVUS) elastography is a new imaging technique that reveals regional mechanical properties of the vascular wall by measuring the local strain. In this study, the Feasibility and potential of the technique during cardiac catheterization are investigated. Presently, nine patients scheduled for percutaneous transluminal coronary angioplasty (PTCA) have been investigated. The intracoronary pressure was used as a mechanical stimulus. Local strain was estimated by cross-correlation analysis of the radio-frequency IVUS signals, obtained from two frames acquired at different pressures. Since errors are incurred with catheter motion, the phase in the heart cycle with minimal catheter motion was determined. The relation between mean strain (average strain value over the full cross-sectional circumference) and the systolo-diastolic change in lumen area was also investigated. Reliable elastographic results were obtained on sequential echo-frames near end-diastole. The elastograms reveal that regions with calcified material (as identified from the echogram) have low strain values: 0 to 0.1%. Normal vessel wall and other plaques demonstrated strain ranging from 0.1 to 1%. A high correlation was found between the mean strain at end diastole and the change in lumen over the cardiac cycle (r/sup 2/=0.81, p=0.005). The results of this preliminary clinical experience suggest that it is feasible to produce clinically useful elastograms.