Numerical study of the uniformity of balloon-expandable stent deployment.

Stents are small tubelike structures, implanted in coronary and peripheral arteries to reopen narrowed vessel sections. This endovascular intervention remains suboptimal, as the success rate is limited by restenosis. This renarrowing of a stented vessel is related to the arterial injury caused by stent-artery and balloon-artery interactions, and a local subsequent inflammatory process. Therefore, efforts to optimize the stent deployment remain very meaningful. Several authors have studied with finite element modeling the mechanical behavior of balloon-expandable stents, but none of the proposed models incorporates the folding pattern of the balloon. We developed a numerical model in which the CYPHER stent is combined with a realistic trifolded balloon. In this paper, the impact of several parameters such as balloon length, folding pattern, and relative position of the stent with respect to the balloon catheter on the free stent expansion has been investigated. Quantitative validation of the modeling strategy shows excellent agreement with data provided by the manufacturer and, therefore, the model serves as a solid basis for further investigations. The parametric analyses showed that both the balloon length and the folding pattern have a considerable influence on the uniformity and symmetry of the transient stent expansion. Consequently, this approach can be used to select the most appropriate balloon length and folding pattern for a particular stent design in order to optimize the stent deployment. Furthermore, it was demonstrated that small positioning inaccuracies may change the expansion behavior of a stent. Therefore, the placement of the stent on the balloon catheter should be accurately carried out, again in order to decrease the endothelial damage.

Coronary microvascular dysfunction after myocardial infarction: increased coronary zero flow pressure both in the infarcted and in the remote myocardium is mainly related to left ventricular filling pressure.

OBJECTIVE: To investigate the underlying mechanisms of a decreased coronary flow reserve after myocardial infarction (MI) by analysing the characteristics of the diastolic hyperaemic coronary pressure-flow relationship. DESIGN: Prospective study. SETTING: Tertiary care hospital. PATIENTS: 68 patients with a recent MI and 27 patients with stable angina pectoris (AP; control group). MAIN OUTCOME MEASURES: The intercept with the pressure axis (the zero flow pressure or Pzf) and slope index of the pressure-flow relationship (SIPF) were calculated from the simultaneously recorded hyperaemic intracoronary blood flow velocity and aortic pressure after successful coronary stenting. RESULTS: A stepwise increase in Pzf from AP (14.6 (8.0) mm Hg), over non-Q-wave MI (22.5 (9.1) mm Hg), to Q-wave MI (37.1 (12.9) mm Hg; p<0.001) was observed. Similar changes in Pzf were found in a reference artery perfusing the non-infarcted myocardium. Multivariate analysis showed that in both regions the left ventricular end-diastolic pressure (LVEDP) was the most important determinant of the Pzf. The SIPF was not statistically different in the treated vessel between patients with MI and AP, but was increased in MI patients with a markedly increased LVEDP. CONCLUSIONS: After an MI, the coronary pressure-flow relationship is shifted to the right both in the infarcted and in the non-infarcted remote myocardium, as shown by the increased Pzf. The correlation with Pzf suggests that elevated left ventricular filling pressures contribute to the impediment of myocardial perfusion in patients with infarction.

Influence of arterial compliance on presence and extent of ischaemia during stress echocardiography.

OBJECTIVE: To seek an association between total arterial compliance (TAC) and the extent of ischaemia at stress echocardiography. DESIGN: Cohort study. SETTING: Regional cardiac centre. METHODS: 255 consecutive patients (147 men; mean (SD) age 58 (8)) presenting for stress echocardiography for clinical indications were studied. Wall motion score index (WMSI) was calculated and ischaemia was defined by an inducible or worsening wall motion abnormality. Peak WMSI was used to reflect the extent of dysfunction (ischaemia or scar), and DeltaWMSI was indicative of extent of ischaemia. TAC was assessed at rest by simultaneous radial applanation tonometry and pulsed wave Doppler in all patients. RESULTS: Ischaemia was identified by stress echocardiography in 65 patients (25%). TAC was similar in the groups with negative and positive echocardiograms (1.08 (0.41) v 1.17 (0.51) ml/mm Hg, not significant). However, the extent of dysfunction was associated with TAC independently of age, blood pressure, risk factors, and use of a beta blocker. Moreover, the extent of ischaemia was determined by TAC, risk factors, and use of a beta blocker. CONCLUSION: While traditional cardiovascular risk factors are strong predictors of ischaemia on stress echocardiography, TAC is an independent predictor of the extent of ischaemia.

Pulse pressure vs. total arterial compliance as a marker of arterial health.

BACKGROUND: Brachial pulse pressure (BPP) is a predictor of outcome in epidemiologic studies, but brachial and aortic pulse pressure (AoPP) may not correspond and both are influenced by multiple parameters including arterial properties and cardiac output. We sought to what extent pulse pressure (PP) measurements reflected direct measurement of arterial properties, assessed as total arterial compliance (TAC). METHODS: We studied 123 patients (76 men; age 55 +/- 11); 31 normal controls, 46 patients with coronary artery disease and 46 patients with hypertension. PP was determined from brachial cuff pressure and TAC was measured by simultaneous radial applanation tonometry and pulsed wave Doppler of the LV outflow. AoPP was calculated using a transfer function from the radial waveform. RESULTS: There was a significant difference between BPP and AoPP (57 +/- 16 vs. 45 +/- 14; P < 0.0001), although TAC correlated with BPP (r = -0.72; P = 0.01) and AoPP (r = -0.66; P = 0.01). In a multiple linear regression, the difference between BPP and AoPP was predicted by cardiac output (CO) (P = 0.002) and gender (P = 0.03). Bland-Altman analysis showed the best correspondence between BPP and AoPP in the middle tertile (CO 4.7 to 5.7 L min(-1)) with less correlation in the low and high tertiles. The same analysis by gender showed a higher difference in women than men (14 +/- 6 vs. 10 +/- 5; P < 0.0001). The difference between BPP and AoPP showed the best correlation in the control group and the worst in the hypertension group. CONCLUSION: BPP correlates with TAC in men with normal cardiac function. However, in women, in patients at the low and high extremes of function, and in patients with preclinical and overt cardiovascular disease, there appears to be incremental value in measuring TAC.

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.

Coronary circulation and interventional cardiology.

Cardiovascular disease has long been the leading cause of death in developed countries and it is rapidly becoming the number one killer in developing countries. Sudden heart attacks remain the primary cause of death in the United States: over 1.4 million attacks are suffered every year, more than half of which prove fatal. Interventional Cardiology is aimed to alleviate symptoms of cardiac pains and poor coronary circulation, and reduce the risk of death and nonfatal myocardial infarction. Our understanding of the coronary circulation has improved several folds due to the introduction of advance technologies. Yet, the microcirculatory flow needs future investigation.

Sonotherapy, antirestenotic therapeutic ultrasound in coronary arteries: the first clinical experience.

We studied the safety and feasibility of intracoronary sonotherapy (IST) and its effect on the coronary vessel at 6 months. Thirty-seven patients with stable or unstable angina were included (40 lesions). The indication was de novo lesion (n = 26), restenosis (n = 2), in-stent restenosis (n = 11), and a total occlusion of a venous bypass graft. After successful angioplasty, IST was performed using a 5 Fr catheter with three serial ultrasound transducers operating at 1 MHz. IST was successfully performed in 36 lesions (success rate, 90%). IST exposure time per lesion was 718 +/- 127 sec. During hospital stay, one patient died due to a bleeding complication. At 6-month follow-up, one patient experienced acute myocardial infarction, eight patients underwent repeat PTCA. No patient underwent CABG. Late lumen loss was 1.05 +/- 0.70 mm with a restenosis rate of 25%. IVUS analysis revealed a neointima burden of 25% +/- 11%. IST can be applied safely and with high acute procedural success. Sonotherapy-related major adverse events were not observed. Late lumen loss and neointimal growth were similar to conventional PTCA approaches. These results justify the initiation of randomized clinical efficacy studies.

Value of coronary stenotic flow velocity acceleration in prediction of angiographic restenosis following balloon angioplasty.

INTRODUCTION: Quantitative angiographic assessment after balloon angioplasty is a poor predictor of immediate and long-term outcome. However, the measurement of blood flow velocity during angioplasty has been proved clinically useful. AIMS: To analyse the value of the maximal stenotic flow velocity and the presence of stenotic flow velocity acceleration (aSV) for the long-term outcome after balloon angioplasty. METHODS AND RESULTS: Patients undergoing single lesion angioplasty within the DEBATE trial were included. aSV was defined as acceleration in the stenotic coronary flow velocity >50% baseline velocity assessed at a reference site of the target vessel. After balloon angioplasty diameter stenosis, minimal lumen diameter (MLD) and coronary flow velocity reserve were similar between the aSV (n=54) and non-aSV group (n=125). At follow-up, the aSV group had a higher restenosis rate (52% vs 30%, P=0.006) The presence of aSV was the strongest independent predictor of restenosis (OR 3.08, 95% CI 1.35 to 7.05, P=0.008). The best predictive cut-off value of SV was 101cm.s(-1) (sensitivity of 46%, specificity of 81%, positive predictive value of 85% and a negative predictive value of 58%). CONCLUSION: Following angioplasty, SV appears to be exquisitely sensitive to the changes experienced at the treated area without depending on the status of the microcirculation.

Morphological and mechanical information of coronary arteries obtained with intravascular elastography; feasibility study in vivo.

AIMS: Plaque composition is a major determinant of coronary related clinical syndromes. In vitro experiments on human coronary and femoral arteries have demonstrated that different plaque types were detectable with intravascular ultrasound elastography. The aim of this study was to investigate the feasibility of applying intravascular elastography during interventional catheterization procedures. METHODS AND RESULTS: Data were acquired in patients (n=12) during PTCA procedures with an EndoSonics InVision echoapparatus equipped with radiofrequency output. The systemic pressure was used to strain the tissue, and the strain was determined using cross-correlation analysis of sequential frames. A likelihood function was determined to obtain the frames with minimal motion of the catheter in the lumen, since motion of the catheter prevents reliable strain estimation. Minimal motion was observed near end-diastole. Reproducible strain estimates were obtained within one pressure cycle and over several pressure cycles. Validation of the results was limited to the information provided by the echogram. Strain in calcified material (0.20%+/-0.07) was lower (P<0.001) than in non-calcified tissue (0.51%+/-0.20). CONCLUSION: In vivo intravascular elastography is feasible. Significantly higher strain values were found in non-calcified plaques than in calcified plaques.

Flow velocity and predictors of a suboptimal coronary flow velocity reserve after coronary balloon angioplasty.

AIMS: This study was conducted to analyse flow velocity parameters and predictors of a suboptimal coronary flow reserve (<2.5) following balloon angioplasty. METHODS: Two hundred and twenty-five patients underwent sequential intracoronary Doppler as part of the DEBATE I study. Of these, 183, with complete angiography and Doppler at the 6-month follow-up, were included. Univariate and multivariate logistic analysis was performed to identify independent predictors of post-procedural suboptimal coronary flow reserve, defined as coronary flow reserve <2.5. RESULTS: Forty-eight per cent (n=88) of the patients achieved a suboptimal coronary flow reserve. These patients had higher baseline velocities (cm.s(-1)) before balloon angioplasty (18+/-9 vs 14+/-6, P=0.004), after balloon angioplasty (22+/-11 vs 14+/-5, P<0.001) and at follow-up (19+/-9 vs 16+/-6, P=0.011) than the optimal coronary flow reserve group. Although the suboptimal group had lower hyperaemic velocities (cm.s(-1)) after balloon angioplasty than the optimal group (42+/-17 vs 49+/-16, P=0.008), these velocities became similar at follow-up. Increasing age (odds ratio, OR 1.071, P=0.0002), female gender (OR 2.52, P=0.014) and increasing pre-procedural baseline average peak velocities (OR 1.056, P<0.001) were found to be independent predictors of a suboptimal coronary flow reserve following balloon angioplasty. CONCLUSION: A suboptimal coronary flow reserve was associated with (1) a chronically elevated baseline average peak velocity (2) a transient deficit in the hyperaemic average peak velocity (3) the elderly, and female gender.

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.

Uncomplicated moderate coronary artery dissections after balloon angioplasty: good outcome without stenting

Objective—To study the relation between moderate coronary dissections, coronary flow velocity reserve (CFVR), and long term outcome. Methods—523 patients undergoing balloon angioplasty and sequential intracoronary Doppler measurements were examined as part of the DEBATE II trial (Doppler endpoints balloon angioplasty trial Europe). After successful balloon angioplasty, patients were randomised to stenting or no further treatment. Dissections were graded at the core laboratory by two observers and divided into four categories: none, mild (type A-B), moderate (type C), severe (types D to F). Patients with severe dissections (n = 128) or without available reference vessel CFVR (n = 139) were excluded. The remaining 256 patients were divided into two groups according to the presence (group A, n = 45) or absence (group B, n = 211) of moderate dissection. Results—Following balloon angioplasty, there was no difference in CFVR between the two groups. At 12 months follow up, a higher rate of major adverse cardiac events was observed overall in group A than in group B (10 (22%) v 23 (11%), p = 0.041). However, the risk of major adverse events was similar in the subgroups receiving balloon angioplasty (group A, 6 (19%) v group B, 16 (16%), NS). Among group A patients, the adverse events risk was greater in those randomised to stenting (odds ratios 6.603 v 1.197, p = 0.046), whereas there was no difference in risk if the group was analysed according to whether the CFVR was 2.5 after balloon angioplasty. Conclusions—Moderate dissections left untreated result in no increased risk of major adverse cardiac events. Additional stenting does not improve the long term outcome.

Uncomplicated moderate coronary artery dissections after balloon angioplasty: good outcome without stenting.

OBJECTIVE: To study the relation between moderate coronary dissections, coronary flow velocity reserve (CFVR), and long term outcome. METHODS: 523 patients undergoing balloon angioplasty and sequential intracoronary Doppler measurements were examined as part of the DEBATE II trial (Doppler endpoints balloon angioplasty trial Europe). After successful balloon angioplasty, patients were randomised to stenting or no further treatment. Dissections were graded at the core laboratory by two observers and divided into four categories: none, mild (type A-B), moderate (type C), severe (types D to F). Patients with severe dissections (n = 128) or without available reference vessel CFVR (n = 139) were excluded. The remaining 256 patients were divided into two groups according to the presence (group A, n = 45) or absence (group B, n = 211) of moderate dissection. RESULTS: Following balloon angioplasty, there was no difference in CFVR between the two groups. At 12 months follow up, a higher rate of major adverse cardiac events was observed overall in group A than in group B (10 (22%) v 23 (11%), p = 0.041). However, the risk of major adverse events was similar in the subgroups receiving balloon angioplasty (group A, 6 (19%) v group B, 16 (16%), NS). Among group A patients, the adverse events risk was greater in those randomised to stenting (odds ratios 6.603 v 1.197, p = 0.046), whereas there was no difference in risk if the group was analysed according to whether the CFVR was < 2.5 or >/= 2.5 after balloon angioplasty. CONCLUSIONS: Moderate dissections left untreated result in no increased risk of major adverse cardiac events. Additional stenting does not improve the long term outcome.

Value of coronary stenotic flow velocity acceleration on the prediction of long-term improvement in functional status after angioplasty.

BACKGROUND: The coronary flow velocity acceleration at the stenotic site (SVA), defined as a > or = 50% increase in resting stenotic velocity when compared with the reference segment, has been shown to be highly sensitive and specific for the diagnosis of a hemodynamically significant stenosis. In this study, we describe the value of postprocedural SVA for the prediction of a lack of improvement in functional activity at long-term follow-up balloon angioplasty (BA). METHODS: We investigated the improvement in functional activity in patients undergoing single native vessel angioplasty and intracoronary Doppler (before BA, after BA, and again at 6-month follow-up) as part of the Doppler Endpoints Balloon Angioplasty Trial Europe (DEBATE) I trial. Lack of improvement was defined as no change in Duke Activity Status Index (DASI) at 6-month follow-up, whereas SVA was defined as > or = 50% elevation in resting velocity at the treated area compared with the distal measurement. RESULTS: SVA was found more frequently in patients without improvement in DASI (45% vs 31%, P =.03). Similar percent diameter stenosis and coronary flow velocity reserve were observed in patients with and those without improvement in DASI at follow-up. By multivariate regression analysis, the presence of SVA (P = .029; odds ratio, 1.97; 95% confidence interval, 1.07 to 3.63) and an elevated DASI at baseline (P < .001; odds ratio, 1.05; 95% confidence interval, 1.03 to 1.07) were associated with a lack of improvement at follow-up. CONCLUSIONS: The detection of SVA was associated with failure of improvement in functional activity at follow-up after coronary intervention.

Comparison of different methods to define a target volume for external beam radiation therapy of restenotic coronary arteries.

PURPOSE: Different methods have been described to define a target volume for the treatment of restenotic (stented) coronary arteries by external beam radiation therapy (EBRT). The purpose of this study was to explore two methods to define a target for such therapy, and to compare these with previously investigated methods. MATERIALS AND METHODS: The 3-D position of a stent throughout the cardiac cycle in the three major epicardial coronary arteries was measured in three patients by single-breathhold multislice spiral CT and breathhold biplane conventional X-ray angiography, both indexed in time with the ECG. The volume through which the stent traversed (STV) during the cardiac cycle was determined by use of displacement measurements. RESULTS: For multislice CT and biplane angiography, respectively, the mean STV was 1.23 cm(3) (range 0.65-2.22 cm(3)) and 2.81 cm(3) (range 1.60-4.99 cm(3)). The STV represented only a fraction of the whole heart volume in all patients, that is, equal to or less than 0.4%. CONCLUSIONS: Multislice CT and biplane angiography allowed the measurement of a relatively small potential target, that is the STV, for EBRT of restenotic stented coronary arteries. Both studied imaging modalities are instrumental for targeting the STV by highly conformal radiation therapy in case of restenotic stented coronary arteries.

Total arterial compliance is a major determinant of peak oxygen uptake.

Total arterial compliance (TAC, defined as dV/dP), is a major component of the arterial system. A decreased TAC increases left ventricular load and has a detrimental effect on coronary perfusion. We sought to assess the influence of TAC on the functional reserve (VO2max). Fourteen patients (mean age 64 +/- 14y) with known or suspected coronary artery disease and eleven controls (34 +/- 5y) underwent supine bicycle exercise echocardiography. Audio Doppler signal output of the echocardiographic machine was digitized with a customized hardware and software interface simultaneously with carotid tonometry and ECG. TAC at rest was calculated by the pulse pressure method (PPM). By step-wise forward multivariate analysis, independent predictors of VO2max were patient versus control status, peak exercise cardiac output and TAC. The described PC-based acquisition system for tonometry and Doppler signals permits the assessment of ventricular function and arterial biomechanics.

Current management of primary pulmonary hypertension.

Primary pulmonary hypertension (PPH) is a rare disorder of the lung vasculature characterised by an increase in pulmonary artery pressure. Although the aetiology of this disease remains unknown, knowledge of the pathophysiology of the disease has advanced considerably. Diagnosis of PPH is largely by exclusion. The clinical symptoms associated with PPH are aspecific and similar to those seen in other cardiovascular and pulmonary diseases. Electrocardiography, echocardiography, pulmonary function tests, and a lung perfusion scan are necessary to exclude secondary forms of pulmonary hypertension and also help to confirm the diagnosis of PPH. A definite diagnosis of PPH is established by right-heart catheterisation which gives a precise measure of the blood pressure in the right side of the heart and the pulmonary artery, right ventricular function and cardiac output. Once a diagnosis of PPH is established, treatment involving drug therapy or surgery is commenced on the basis of the New York Heart Association functional class. Conventional treatment consists of lifetime administration of anticoagulants, oxygen, diuretics, and digoxin. Vasodilator therapy with calcium channel antagonists is indicated in patients who are 'vasoreactive' to acute vasodilator challenge as assessed by right-heart catheterisation. Promising results are obtained by continuous intravenous administration of epoprostenol (prostacyclin). Newer therapies for PPH include prostacyclin analogues, endothelin receptor antagonists, nitric oxide, phosphodiesterase-5 inhibitors, elastase inhibitors, and gene therapy. Surgical treatment consists of atrial septostomy, thromboendarterectomy, and lung or heart-lung transplantation.

Relationship between tensile stress and plaque growth after balloon angioplasty treated with and without intracoronary beta-brachytherapy.

AIMS: We investigated the influence of tensile stress on plaque growth after balloon angioplasty with and without beta-radiation therapy. METHODS AND RESULTS: Thirty-one consecutive patients successfully treated with balloon angioplasty were analysed qualitatively and quantitatively by means of an ECG-gated three-dimensional intravascular ultrasound post-procedure and at follow-up. Eighteen patients were irradiated with catheter-based beta-radiation ((90)Sr/(90)Y source) and 13 were not (control). Studied segments were divided into 2 mm subsegments. Thus 184 irradiated and 111 non-irradiated subsegments were included. Tensile stress was calculated according to Laplace's law. The radiation dose was calculated by means of dose-volume histograms. Plaque growth was positively correlated to tensile stress in both the radiation and control groups (r=0.374, P=0.0001 and r=0.305, P=0.001). Low-dose subsegments (<6 Gy) had a significant correlation (r=0.410, P=0.0001) whereas no correlation was observed in the effective-dose subsegments (> or = 6 Gy). Multivariate analysis identified tensile stress as the only independent predictor of plaque increase in non-irradiated subsegments, whereas actual dose and plaque morphology were stronger predictors in irradiated subsegments. CONCLUSION: The results of this study suggest that plaque growth is related to tensile stress after balloon angioplasty. Intracoronary brachytherapy may alter the biophysical process on plaque growth when the prescribed dose is effectively delivered.