Attila Thury

Strain distribution over plaques in human coronary arteries relates to shear stress

Once plaques intrude into the lumen, the shear stress they are exposed to alters with hitherto unknown consequences for plaque composition. We investigated the relationship between shear stress and strain, a marker for plaque composition, in human coronary arteries. We imaged 31 plaques in coronary arteries with angiography and intravascular ultrasound. Computational fluid dynamics was used to obtain shear stress. Palpography was applied to measure strain. Each plaque was divided into four regions: upstream, throat, shoulder, and downstream. Average shear stress and strain were determined in each region. Shear stress in the upstream, shoulder, throat, and downstream region was 2.55+/-0.89, 2.07+/-0.98, 2.32+/-1.11, and 0.67+/-0.35 Pa, respectively. Shear stress in the downstream region was significantly lower. Strain in the downstream region was also significantly lower than the values in the other regions (0.23+/-0.08% vs. 0.48+/-0.15%, 0.43+/-0.17%, and 0.47+/-0.12%, for the upstream, shoulder, and throat regions, respectively). Pooling all regions, dividing shear stress per plaque into tertiles, and computing average strain showed a positive correlation; for low, medium, and high shear stress, strain was 0.23+/-0.10%, 0.40+/-0.15%, and 0.60+/-0.18%, respectively. Low strain colocalizes with low shear stress downstream of plaques. Higher strain can be found in all other plaque regions, with the highest strain found in regions exposed to the highest shear stresses. This indicates that high shear stress might destabilize plaques, which could lead to plaque rupture.

Simulation of stent deployment in a realistic human coronary artery

BackgroundThe process of restenosis after a stenting procedure is related to local biomechanical environment. Arterial wall stresses caused by the interaction of the stent with the vascular wall and possibly stress induced stent strut fracture are two important parameters. The knowledge of these parameters after stent deployment in a patient derived 3D reconstruction of a diseased coronary artery might give insights in the understanding of the process of restenosis.Methods3D reconstruction of a mildly stenosed coronary artery was carried out based on a combination of biplane angiography and intravascular ultrasound. Finite element method computations were performed to simulate the deployment of a stent inside the reconstructed coronary artery model at inflation pressure of 1.0 MPa. Strut thickness of the stent was varied to investigate stresses in the stent and the vessel wall.ResultsDeformed configurations, pressure-lumen area relationship and stress distribution in the arterial wall and stent struts were studied. The simulations show how the stent pushes the arterial wall towards the outside allowing the expansion of the occluded artery. Higher stresses in the arterial wall are present behind the stent struts and in regions where the arterial wall was thin. Values of 200 MPa for the peak stresses in the stent strut were detected near the connecting parts between the stent struts, and they were only just below the fatigue stress. Decreasing strut thickness might reduce arterial damage without increasing stresses in the struts significantly.ConclusionThe method presented in this paper can be used to predict stresses in the stent struts and the vessel wall, and thus evaluate whether a specific stent design is optimal for a specific patient.

Radioactive Stents Delay but Do Not Prevent In-Stent Neointimal Hyperplasia

Background—Restenosis after conventional stenting is almost exclusively caused by neointimal hyperplasia. &bgr;-Particle–emitting radioactive stents decrease in-stent neointimal hyperplasia at 6-month follow-up. The purpose of this study was to evaluate the 1-year outcome of 32P radioactive stents with an initial activity of 6 to 12 &mgr;Ci using serial quantitative coronary angiography and volumetric ECG-gated 3D intravascular ultrasound (IVUS). Methods and Results—Of 40 patients undergoing initial stent implantation, 26 were event-free after the 6-month follow-up period and 22 underwent repeat catheterization and IVUS at 1 year; they comprised half of the study population. Significant luminal deterioration was observed within the stents between 6 months and 1 year, as evidenced by a decrease in the angiographic minimum lumen diameter (−0.43±0.56 mm;P =0.028) and in the mean lumen diameter in the stent (−0.55±0.63 mm;P =0.001); a significant increase in in-stent neointimal hyperplasia by IVUS (18.16±12.59 mm3 at 6 months to 27.75±11.99 mm3 at 1 year;P =0.001) was also observed. Target vessel revascularization was performed in 5 patients (23%). No patient experienced late occlusion, myocardial infarction, or death. By 1 year, 21 of the initial 40 patients (65%) remained event-free. Conclusions—Neointimal proliferation is delayed rather than prevented by radioactive stent implantation. Clinical outcome 1 year after the implantation of stents with an initial activity of 6 to 12 &mgr;Ci is not favorable when compared with conventional stenting.

Images in cardiovascular medicine. Focal in-stent restenosis near step-up: roles of low and oscillating shear stress?

A 64-year-old man with exercise-induced chest pain underwent coronary angioplasty of his stenosed left anterior descending coronary artery (segments 6 and 7). We recanalized the artery and placed a 3.0×18-mm stent distally and a 3.0×28-mm stent proximally. The residual diameter stenosis at the proximal edge was 26% on quantitative coronary angiography (QCA). Intravascular ultrasound (IVUS) showed an in-stent lumen area of 7.5 mm2, which exceeded that immediate proximal of the stent (5.6±0.8 mm2) and caused a so-called “step-up” phenomenon (Figure 1A and 1B, open arrow). Although the stent was well apposed and deployed as indicated by IVUS, the patient presented with worsening anginal symptoms 4 months later; both the angiogram and IVUS showed focal in-stent restenosis at the proximal edge of the proximal stent (78% on QCA) and mild diffuse neointimal hyperplasia (NIH) through the entire length of the stent. Figure 1. A, Lateral angiographic view …

Is Bare-Metal Stent Implantation Still Justifiable in High Bleeding Risk Patients Undergoing Percutaneous Coronary Intervention?: A Pre-Specified Analysis From the ZEUS Trial.

OBJECTIVES This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease. BACKGROUND DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns. METHODS The ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) is a multinational, randomized single-blinded trial that randomized among others, in a stratified manner, 828 patients fulfilling pre-defined clinical or biochemical HBR criteria-including advanced age, indication to oral anticoagulants or other pro-hemorrhagic medications, history of bleeding and known anemia-to receive E-ZES or BMS followed by a protocol-mandated 30-day DAPT regimen. The primary endpoint of the study was the 12-month major adverse cardiovascular event rate, consisting of death, myocardial infarction, or target vessel revascularization. RESULTS Compared with patients without, those with 1 or more HBR criteria had worse outcomes, owing to higher ischemic and bleeding risks. Among HBR patients, major adverse cardiovascular events occurred in 22.6% of the E-ZES and 29% of the BMS patients (hazard ratio: 0.75; 95% confidence interval: 0.57 to 0.98; p = 0.033), driven by lower myocardial infarction (3.5% vs. 10.4%; p < 0.001) and target vessel revascularization (5.9% vs. 11.4%; p = 0.005) rates in the E-ZES arm. The composite of definite or probable stent thrombosis was significantly reduced in E-ZES recipients, whereas bleeding events did not differ between stent groups. CONCLUSIONS Among HBR patients with stable or unstable coronary artery disease, E-ZES implantation provides superior efficacy and safety as compared with conventional BMS. (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS]; NCT01385319).

Five-year experience with transradial coronary angioplasty in ST-segment-elevation myocardial infarction

BACKGROUND AND PURPOSE Percutaneous coronary intervention (PCI) via radial approach has been shown to be an alternative to femoral approach in emergency cases; however, its feasibility has been questioned. This single-center study was performed to compare the outcomes and complication rates between transradial (TR) and transfemoral (TF) PCI in ST-segment-elevation myocardial infarction (STEMI). METHODS AND MATERIALS The clinical and angiographic data of 582 consecutive STEMI patients treated with PCI between 2001 and 2006 were evaluated in a retrospective study. Forty-three patients were excluded from the present study due to cardiogenic shock or rescue PCI. Patients (n=539) were categorized into the TR group (n=167) or the TF group (n=372), and several parameters were evaluated to assess the advantages and drawbacks of TR access: access-site crossover, rate of access-site complications, procedure time, fluoroscopy time, X-ray area dose, major adverse cardiac events (MACE) at 1 month, and consumption of angioplasty equipment. RESULTS In the TR group, the crossover rate to femoral access was 5%, while in the TF group, it was 0.8% (P<.05). There was a significant difference, in both major and minor access-site complications, between the TR group and the TF group (0% vs. 5%, P<.05, and 4% vs. 9%, P<.05, respectively). Consumption of angioplasty equipment proved to be the same for the two groups. The MACE rate was 4% in the TR group and 11% in the TF group (P<.05). CONCLUSIONS Our results suggest that the TR approach is a safe and effective way to treat STEMI; furthermore, site-related complications are less common with this approach.

The effect of aortic valve replacement on coronary flow reserve in patients with a normal coronary angiogram.

Background: In patients with aortic stenosis and a normal coronary angiogram, a coronary flow reserve (CFR) is impaired. The aim of the present study was to examine the effect of aortic valve replacement (AVR) on the CFR after a long-term follow-up. Patients and Methods: 30 patients with aortic stenosis and a normal coronary angiogram were enrolled in the study. CFR measurements were made on 21 patients 123 ± 137 days before and 497 ± 167 days after AVR. CFR measurements were carried out according to a standard protocol, with a vasodilator stimulus dipyridamole (0.56 mg/kg for 4 min) and peak diastolic velocity measurements at 6 min. Results: Initially, the average peak gradient of aortic stenosis was 89.5 ± 22.4 mm Hg. After AVR, it decreased to 26.2 ± 9 mm Hg. Left ventricular mass was significantly lower after AVR: 354.9 ± 107.9 g versus 223.8 ± 73.6 g (p < 0.001). The average baseline diastolic velocity measured by pulsed Doppler in the left anterior descending coronary artery amounted to 62.2 ± 25.5 cm/s before and 40.1 ± 13.6 cm/s after AVR. The difference was statistically significant (p < 0.01). The average diastolic velocity at maximum stress equaled 117 ± 42.8 cm/s pre- and 91.5 ± 34 cm/s postoperatively (p < 0.005). The calculated CFR before AVR amounted to 1.96 ± 0.5 and increased to 2.37 ± 0.8 postoperatively. The difference was statistically significant (p < 0.05). Conclusion: Prosthetic AVR is of considerable benefit concerning the CFR in patients with a normal coronary angiogram after a long-term follow-up.Hintergrund: Bei Patienten mit Aortenklappenstenose und anatomisch normalem Koronarsystem ist die Koronarflussreserve (CFR) vermindert. Ziel dieser Studie war, die Auswirkungen von Aortenklappenersatzoperationen (AVR) auf die CFR im Langzeitverlauf zu untersuchen. Patienten und Methodik: 30 Patienten mit Aortenklappenstenose wurden in die Studie einbezogen. Die CFR wurde bei 21 Patienten 123 ± 137 Tage vor und 497 ± 167 Tage nach AVR mit einer standardisierten echokardiographischen Methode transösophageal bestimmt. Die Doppler-Messungen erfolgten im Normalzustand und nach maximaler Vasodilatation durch 4-min-Infusion von 0,56 mg/kg Dipyridamol. Ergebnisse: Der durchschnittliche Druckgradient über den Aortenklappen lag bei 89,5 ± 22,4 mm Hg vor und 26,2 ± 9 mm Hg nach AVR. Das linksventrikuläre Gewicht war nach der Operation signifikant vermindert (354,9 ± 107,9 vs. 223,8 ± 73,6 g; p < 0.001). Die durchschnittliche diastolische Geschwindigkeit in den Ramus-interventricularis-anterior-Arterien lag präoperativ bei 62,2 ± 25,5 cm/s und postoperativ bei 40,1 ± 13,6 cm/s (p < 0.01). Die durchschnittliche diastolische Geschwindigkeit bei maximaler Vasodilatation betrug 117 ± 42,8 cm/s vor und 91,5 ± 34 cm/s nach AVR (p < 0.05). Der kalkulierte CFR-Wert lag präoperativ bei 1,96 ± 0,5 und erhöhte sich nach der Operation auf 2,37 ± 0,8 (p < 0,05). Schlussfolgerung: Die Implantation von Aortenklappenprothesen hat eine positive Wirkung auf die CFR von Patienten mit anatomisch normalen Koronararterien.

The comparative value of the aortic atherosclerosis and the coronary flow velocity reserve evaluated by stress transesophageal echocardiography in the prediction of patients with aortic stenosis with coronary artery disease.

Background: The present study was conducted to examine whether it is possible to differentiate patients with aortic stenosis (AOS) with or without significant stenosis of the left anterior descending coronary artery (LAD) on the basis of the age, gender, hypertension, diabetes mellitus, hypercholesterolemia, the coronary flow velocity reserve (CFVR) and the grade of aortic atherosclerosis (AA) evaluated by TEE in the course of the same semi-invasive examination. Patients and methods: Thirty-nine consecutive AOS patients who had undergone coronary angiography were examined by dipyridamole stress TEE to assess the CFVR. From this patient population, 21 AOS patients with anatomically normal coronary arteries (group 1), and 18 AOS patients with >75% stenosis of the LAD (group 2) were selected for the present study. The CFVR was calculated as the ratio of the average peak diastolic flow velocity (APV) during hyperemia to the resting APV. The grade of AA in the descending aorta was determined by means of the same TEE examination. Results: The demographic, clinical and transthoracic echocardiographic data, the coronary flow velocities and the CFVRs were similar in the two patient groups. Only the grade of AA (ROC area, 73%, p <0.02) appears useful for the distinction of AOS patients with or without significant LAD stenosis. Conclusions: These results demonstrate that only the grade of AA furnishes additional help in the prediction of AOS patients with severe LAD disease. CFVR has no any diagnostic power in the differentiation of AOS patients with or without significant LAD stenosis.

Focus on the research utility of intravascular ultrasound - comparison with other invasive modalities

Intravascular ultrasound (IVUS) is an invasive modality which provides cross-sectional images of a coronary artery. In these images both the lumen and outer vessel wall can be identified and accurate estimations of their dimensions and of the plaque burden can be obtained. In addition, further processing of the IVUS backscatter signal helps in the characterization of the type of the plaque and thus it has been used to study the natural history of the atherosclerotic evolution. On the other hand its indigenous limitations do not allow IVUS to assess accurately stent struts coverage, existence of thrombus or exact site of plaque rupture and to identify some of the features associated with increased plaque vulnerability. In order this information to be obtained, other modalities such as optical coherence tomography, angioscopy, near infrared spectroscopy and intravascular magnetic resonance imaging have either been utilized or are under evaluation. The aim of this review article is to present the current utilities of IVUS in research and to discuss its advantages and disadvantages over the other imaging techniques.

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. Catheter Cardiovasc Interv 2003;60:9–17.