A Clinician's Contribution to Biomedical Engineering in Experimental Echocardiography

The research of this thesis has been focused on the biomedical engineering aspects of new techniques of echocardiography. In close collaboration with the engineers of the Experimental Echocardiography Department of the Thoraxcentre, Erasmus University, Rotterdam, new methods to measure coronary blood flow and arterial wall elasticity with intravascular ultrasound (IVUS) have been developed. We have also investigated the clinical application of these measurements and have tried to improve traditional techniques based on intracoronary Doppler wires. In another field, we have developed a method to determine the radiation dose delivered in the wall of coronary arteries treated with brachytherapy. in collaboration with the Emory University, Atlanta, GA. This method utilizes 3-dimensional IVUS reconstruction combined with radiotherapy treatment planning. Finally, the tools developed for the recording of the signals of intracoronary Doppler wires have been adapted, during a stay at the Cleveland Clinic Foundation, OK for the study of left ventricular mechanics and the compliance of the large arteries. This has been achieved by simultaneous acquisition of non-invasive pressure (with tonometry) and flow (with transthoracic Doppler echocardiography) signals. The fruits of an old and close collaboration with the Institute Biomedical Technology of the Ghent University can also be found in different chapters. This work is subdivided in five major parts, and a detailed introductory chapter precedes each one

Decreased coronary flow reserve in hypertrophic cardiomyopathy is related to remodeling of the coronary microcirculation

BACKGROUND: Ischemia occurs frequently in hypertrophic cardiomyopathy (HCM) without evidence of epicardial stenosis. This study evaluates the hypothesis that the occurrence of ischemia in HCM is related to remodeling of the coronary microcirculation. METHODS AND RESULTS: End-diastolic septal wall thickness was significantly increased in patients with HCM (25.8+/-2.9 mm) in comparison with cardiac transplant recipients (control subjects: 11.4+/-3.0 mm; P<0.05). Although the diameter of the left anterior descending coronary artery was similar in both groups (3.0+/-0.8 versus 3.0+/-0.5 mm, P=NS), the coronary resistance reserve (CRR=CRRbasal/CRRhyperemic), corrected for extravascular compression (end-diastolic left ventricular pressure), was reduced to 1.5+/-0.6 in HCM (P<.05; control, 2.6+/-0.8). Arteriolar lumen (AL) divided by wall area was lower in HCM (21+/-5% versus 30+/-4%; P<.05), and capillary density tended to decrease (from 1824+/-424 to 1445+/-513 per mm2, P=.11) in HCM. CRR was linearly related to normalized AL according to the formula CRR=O.1 AL-0.45 (r=.57; P<.05). Further analysis revealed that CRR, AL, and capillary density were all linearly related to the degree of hypertrophy. CONCLUSIONS: Decrements in CRR were related to changes of the coronary microcirculation. Both the decrease in CRR and these changes in the coronary microcirculation were related to the degree of hypertrophy. All these factors might contribute to the well-known occurrence of ischemia in this patient group

Preserved endothelium-dependent vasodilation in coronary segments previously treated with balloon angioplasty and intracoronary irradiation

BACKGROUND: Abnormal endothelium-dependent coronary vasomotion has been reported after balloon angioplasty (BA), as well as after intracoronary radiation. However, the long-term effect on coronary vasomotion is not known. The aim of this study was to evaluate the long-term vasomotion of coronary segments treated with BA and brachytherapy. METHODS AND RESULTS: Patients with single de novo lesions treated either with BA followed by intracoronary beta-irradiation (according to the Beta Energy Restenosis Trial-1.5) or with BA alone were eligible. Of these groups, those patients in stable condition who returned for 6-month angiographic follow-up formed the study population (n=19, irradiated group and n=11, control group). Endothelium-dependent coronary vasomotion was assessed by selective infusion of serial doses of acetylcholine (ACh) proximally to the treated area. Mean luminal diameter was calculated by quantitative coronary angiography both in the treated area and in distal segments. Endothelial dysfunction was defined as a vasoconstriction after the maximal dose of ACh (10(-6) mol/L). Seventeen irradiated segments (89.5%) demonstrated normal endothelial function. In contrast, 10 distal nonirradiated segments (53%) and 5 control segments (45%) demonstrated endothelium-dependent vasoconstriction (-19+/-17% and -9.0+/-5%, respectively). Mean percentage of change in mean luminal diameter after ACh was significantly higher in irradiated segments (P=0.01). CONCLUSIONS: Endothelium-dependent vasomotion of coronary segments treated with BA followed by beta-radiation is restored in the majority of stabl

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

Outcome from balloon induced coronary artery dissection after intracoronary beta radiation

OBJECTIVE: To evaluate the healing of balloon induced coronary artery dissection in individuals who have received beta radiation treatment and to propose a new intravascular ultrasound (IVUS) dissection score to facilitate the comparison of dissection through time. DESIGN: Retrospective study. SETTING: Tertiary referral centre. PATIENTS: 31 patients with stable angina pectoris, enrolled in the beta energy restenosis trial (BERT-1.5), were included. After excluding those who underwent stent implantation, the evaluable population was 22 patients. INTERVENTIONS: Balloon angioplasty and intracoronary radiation followed by quantitative coronary angiography (QCA) and IVUS. Repeat QCA and IVUS were performed at six month follow up. MAIN OUTCOME MEASURES: QCA and IVUS evidence of healing of dissection. Dissection classification for angiography was by the National Heart Lung Blood Institute scale. IVUS proven dissection was defined as partial or complete. The following IVUS defined characteristics of dissection were described in the affected coronary segments: length, depth, arc circumference, presence of flap, and dissection score. Dissection was defined as healed when all features of dissection had resolved. The calculated dose of radiation received by the dissected area in those with healed versus non-healed dissection was also compared. RESULTS: Angiography (type A = 5, B = 7, C = 4) and IVUS proven (partial = 12, complete = 4) dissections were seen in 16 patients following intervention. At six month follow up, six and eight unhealed dissections were seen by angiography (A = 2, B = 4) and IVUS (partial = 7, complete = 1), respectively. The mean IVUS dissection score was 5.2 (range 3-8) following the procedure, and 4.6 (range 3-7) at follow up. No correlation was found between the dose prescribed in the treated area and the presence of unhealed disse

Randomized comparison of primary stenting and provisional balloon angioplasty guided by flow velocity measurement.

BACKGROUND: Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may have other disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive. METHODS AND RESULTS: To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is "optimal." An optimal result was defined as a flow reserve >2.5 and a diameter stenosis <36%. Bailout stenting was needed in 129 patients (25%) who were randomized to balloon angioplasty, and an optimal result was obtained in 184 of the 523 patients (35%). There was no significant difference in event-free survival at 1 year between primary stenting (86.6%) and provisional angioplasty (85.6%). Costs after 1 year were significantly higher for provisional angioplasty (EUR 6573 versus EUR 5885; P:=0.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P:=0. 066). CONCLUSIONS: After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty

Residual Plaque Burden, Delivered Dose, and Tissue Composition Predict 6-Month Outcome After Balloon Angioplasty and Beta-Radiation Therapy

Background—Inhomogeneity of dose distribution and anatomic aspects of the atherosclerotic plaque may influence the outcome of irradiated lesions after balloon angioplasty (BA). We evaluated the influence of delivered dose and morphological characteristics of coronary stenoses treated with ß-radiation after BA. Methods and Results—Eighteen consecutive patients treated according to the Beta Energy Restenosis Trial 1.5 were included in the study. The site of angioplasty was irradiated with the use of a ß-emitting 90Sr/90Y source. With the side branches used as anatomic landmarks, the irradiated area was identified and volumetric assessment was performed by 3D intracoronary ultrasound imaging after treatment and at 6 months. The type of tissue, the presence of dissection, and the vessel volumes were assessed every 2 mm within the irradiated area. The minimal dose absorbed by 90% of the adventitial volume (Dv90Adv) was calculated in each 2-mm segment. Diffuse calcified subsegments and those containing side branches were excluded. Two hundred six coronary subsegments were studied. Of those, 55 were defined as soft, 129 as hard, and 22 as normal/intimal thickening. Plaque volume showed less increase in hard segments as compared with soft and normal/intimal thickening segments (P<0.0001). Dv90Adv was associated with plaque volume at follow-up after a polynomial equation with linear and nonlinear components (r=0.71; P=0.0001). The multivariate regression analysis identified the independent predictors of the plaque volume at follow-up: plaque volume after treatment, Dv90Adv, and type of plaque. Conclusions—Residual plaque burden, delivered dose, and tissue composition play a fundamental role in the volumetric outcome at 6-month follow-up after ß-radiation therapy and BA