Cost-effectiveness analysis of paclitaxel-coated balloons for endovascular therapy of femoropopliteal arterial obstructions.

PURPOSE To explore the cost-effectiveness of using drug-eluting balloon (DEB) angioplasty for the treatment of femoropopliteal arterial lesions, which has been shown to significantly lower the rates of target lesion revascularization (TLR) compared with standard balloon angioplasty (BA). METHODS A simplified decision-analytic model based on TLR rates reported in the literature was applied to baseline and follow-up costs associated with in-hospital patient treatment during 1 year of follow-up. Costs were expressed in Swiss Francs (sFr) and calculated per 100 patients treated. Budgets were analyzed in the context of current SwissDRG reimbursement figures and calculated from two different perspectives: a general budget on total treatment costs (third-party healthcare payer) as well as a budget focusing on the physician/facility provider perspective. RESULTS After 1 year, use of DEB was associated with substantially lower total inpatient treatment costs when compared with BA (sFr 861,916 vs. sFr 951,877) despite the need for a greater investment at baseline related to higher prices for DEBs. In the absence of dedicated reimbursement incentives, however, use of DEB was shown to be the financially less favorable treatment approach from the physician/facility provider perspective (12-month total earnings: sFr 179,238 vs. sFr 333,678). CONCLUSION Use of DEBs may be cost-effective through prevention of TLR at 1 year of follow-up. The introduction of dedicated financial incentives aimed at improving DEB reimbursements may help lower total healthcare costs.

Revascularisation versus medical treatment in patients with stable coronary artery disease: network meta-analysis

OBJECTIVE To investigate whether revascularisation improves prognosis compared with medical treatment among patients with stable coronary artery disease. DESIGN Bayesian network meta-analyses to combine direct within trial comparisons between treatments with indirect evidence from other trials while maintaining randomisation. ELIGIBILITY CRITERIA FOR SELECTING STUDIES A strategy of initial medical treatment compared with revascularisation by coronary artery bypass grafting or Food and Drug Administration approved techniques for percutaneous revascularization: balloon angioplasty, bare metal stent, early generation paclitaxel eluting stent, sirolimus eluting stent, and zotarolimus eluting (Endeavor) stent, and new generation everolimus eluting stent, and zotarolimus eluting (Resolute) stent among patients with stable coronary artery disease. DATA SOURCES Medline and Embase from 1980 to 2013 for randomised trials comparing medical treatment with revascularisation. MAIN OUTCOME MEASURE All cause mortality. RESULTS 100 trials in 93 553 patients with 262 090 patient years of follow-up were included. Coronary artery bypass grafting was associated with a survival benefit (rate ratio 0.80, 95% credibility interval 0.70 to 0.91) compared with medical treatment. New generation drug eluting stents (everolimus: 0.75, 0.59 to 0.96; zotarolimus (Resolute): 0.65, 0.42 to 1.00) but not balloon angioplasty (0.85, 0.68 to 1.04), bare metal stents (0.92, 0.79 to 1.05), or early generation drug eluting stents (paclitaxel: 0.92, 0.75 to 1.12; sirolimus: 0.91, 0.75 to 1.10; zotarolimus (Endeavor): 0.88, 0.69 to 1.10) were associated with improved survival compared with medical treatment. Coronary artery bypass grafting reduced the risk of myocardial infarction compared with medical treatment (0.79, 0.63 to 0.99), and everolimus eluting stents showed a trend towards a reduced risk of myocardial infarction (0.75, 0.55 to 1.01). The risk of subsequent revascularisation was noticeably reduced by coronary artery bypass grafting (0.16, 0.13 to 0.20) followed by new generation drug eluting stents (zotarolimus (Resolute): 0.26, 0.17 to 0.40; everolimus: 0.27, 0.21 to 0.35), early generation drug eluting stents (zotarolimus (Endeavor): 0.37, 0.28 to 0.50; sirolimus: 0.29, 0.24 to 0.36; paclitaxel: 0.44, 0.35 to 0.54), and bare metal stents (0.69, 0.59 to 0.81) compared with medical treatment. CONCLUSION Among patients with stable coronary artery disease, coronary artery bypass grafting reduces the risk of death, myocardial infarction, and subsequent revascularisation compared with medical treatment. All stent based coronary revascularisation technologies reduce the need for revascularisation to a variable degree. Our results provide evidence for improved survival with new generation drug eluting stents but no other percutaneous revascularisation technology compared with medical treatment.

Functional assessment of collaterals in the human coronary circulation.

The coronary collateral circulation is an alternative source of blood supply to a myocardial area jeopardized by the failure of the stenotic or occluded vessel to provide enough blood flow to this region. Until recently, only qualitative or semiqualitative methods have been available for the assessment of the coronary collateral circulation in humans, such as the patient's history of walk-through angina pectoris, the registration of intracoronary ECG signs for myocardial ischaemia or angina pectoris during coronary occlusion, or coronary angiographic classification (score 0-3) of collaterals. Studies of coronary wedge pressure measurements distal of a balloon-occluded coronary artery and the recent advent of ultrathin pressure and Doppler angioplasty guidewires have made it possible to obtain pressure or flow velocity data in remote vascular areas and, thus, to calculate functional variables for coronary collateral flow. Those coronary occlusive pressure- and flow velocity-derived parameters express collateral flow as a fraction of antegrade coronary flow during vessel patency of the collateral-receiving vessel. They are both interchangeable, and they have been validated in comparison to 'traditional' methods and against each other. The possibility of accurately measuring coronary collateral flow indices in humans undergoing coronary balloon angioplasty opens areas of investigation of the pathogenesis, pathophysiology and therapeutic promotion of the collateral circulation previously reserved for exclusively experimental studies. The purpose of this article is to review several clinically available methods for the functional characterization of the coronary collateral circulation.

Ultrasound-assisted versus conventional catheter-directed thrombolysis for acute iliofemoral deep vein thrombosis

BACKGROUND For patients with acute iliofemoral deep vein thrombosis, it remains unclear whether the addition of intravascular high-frequency, low-power ultrasound energy facilitates the resolution of thrombosis during catheter-directed thrombolysis. METHODS AND RESULTS In a controlled clinical trial, 48 patients (mean age 50±21 years, 52% women) with acute iliofemoral deep vein thrombosis were randomized to receive ultrasound-assisted catheter-directed thrombolysis (N=24) or conventional catheter-directed thrombolysis (N=24). Thrombolysis regimen (20 mg r-tPA over 15 hours) was identical in all patients. The primary efficacy end point was the percentage of thrombus load reduction from baseline to 15 hours according to the length-adjusted thrombus score, obtained from standardized venograms and evaluated by a core laboratory blinded to group assignment. The percentage of thrombus load reduction was 55%±27% in the ultrasound-assisted catheter-directed thrombolysis group and 54%±27% in the conventional catheter-directed thrombolysis group (P=0.91). Adjunctive angioplasty and stenting was performed in 19 (80%) patients and in 20 (83%) patients, respectively (P>0.99). Treatment-related complications occurred in 3 (12%) and 2 (8%) patients, respectively (P>0.99). At 3-month follow-up, primary venous patency was 100% in the ultrasound-assisted catheter-directed thrombolysis group and 96% in the conventional catheter-directed thrombolysis group (P=0.33), and there was no difference in the severity of the post-thrombotic syndrome (mean Villalta score: 3.0±3.9 [range 0-15] versus 1.9±1.9 [range 0-7]; P=0.21), respectively. CONCLUSIONS In this randomized controlled clinical trial of patients with acute iliofemoral deep vein thrombosis treated with a fixed-dose catheter thrombolysis regimen, the addition of intravascular ultrasound did not facilitate thrombus resolution. CLINICAL TRIAL REGISTRATION URL http://www.clinicaltrials.gov. Unique identifier: NCT01482273.

Aortic valve replacement and concomitant procedures with the Perceval valve: results of European trials.

BACKGROUND The Perceval (Sorin Group, Milan, Italy) is a self-anchoring sutureless aortic valve prosthesis. We report the short- to midterm results of combined aortic valve replacement (AVR) with concomitant procedures in elderly patients undergoing operation as part of 3 consecutive prospective multicenter European studies. METHODS From April 2007 to February 2013, 243 patients (mean age, 79.7 ± 5.1 years; female patients, 61%; median EuroSCORE, 9%) underwent AVR with concomitant procedures. The concomitant procedures were coronary artery bypass grafting (CABG) (182 cases), septal myectomy (21 cases), CABG + other procedures (18 cases), and 22 other procedures. Primary and secondary end points included implant feasibility and safety (for mortality and morbidity) and efficacy (New York Heart Association [NYHA] class improvement and hemodynamic results) of the prosthesis at the different follow-up periods. Data were expressed as mean ± standard deviation. Kaplan-Meier analysis was performed for survival analysis. RESULTS Mean aortic cross-clamp and extracorporeal circulation (ECC) times were 50.7 ± 22.8 minutes and 78.9 ± 32.3 minutes, respectively. Thirty-day mortality was 2.1%. Mean postoperative gradient and effective orifice area were 10.1 ± 4.7 mm Hg and 1.5 ± 0.4 cm(2) and 8.9 ± 5.6 mm Hg and 1.6 ± 0.4 cm(2), respectively, at 1 year. There were early explantations, 4 of which resulted from paravalvular leaks. One additional valve explantation resulted from aortic root bleeding, probably caused by excessively extensive decalcification. In the late period, there was 1 mild paravalvular leak and no intravalvular insufficiency. No migration, dislodgement, or degeneration of the valve occurred during follow-up. Median follow-up was 444 days. CONCLUSIONS These trials confirm the safety and efficacy of the Perceval sutureless aortic valve, especially in elderly patients requiring AVR + concomitant procedures. In this patient group, sutureless valves may be advantageous compared to transcatheter valve implantations as concomitant procedures other than percutaneous coronary artery angioplasty are not always possible in the latter.

Percutaneous coronary interventional strategies for treatment of in-stent restenosis: a network meta-analysis.

BACKGROUND Percutaneous coronary intervention (PCI) with drug-eluting stents is the standard of care for treatment of native coronary artery stenoses, but optimum treatment strategies for bare metal stent and drug-eluting stent in-stent restenosis (ISR) have not been established. We aimed to compare and rank percutaneous treatment strategies for ISR. METHODS We did a network meta-analysis to synthesise both direct and indirect evidence from relevant trials. We searched PubMed, the Cochrane Library Central Register of Controlled Trials, and Embase for randomised controlled trials published up to Oct 31, 2014, of different PCI strategies for treatment of any type of coronary ISR. The primary outcome was percent diameter stenosis at angiographic follow-up. This study is registered with PROSPERO, number CRD42014014191. FINDINGS We deemed 27 trials eligible, including 5923 patients, with follow-up ranging from 6 months to 60 months after the index intervention. Angiographic follow-up was available for 4975 (84%) of 5923 patients 6-12 months after the intervention. PCI with everolimus-eluting stents was the most effective treatment for percent diameter stenosis, with a difference of -9·0% (95% CI -15·8 to -2·2) versus drug-coated balloons (DCB), -9·4% (-17·4 to -1·4) versus sirolimus-eluting stents, -10·2% (-18·4 to -2·0) versus paclitaxel-eluting stents, -19·2% (-28·2 to -10·4) versus vascular brachytherapy, -23·4% (-36·2 to -10·8) versus bare metal stents, -24·2% (-32·2 to -16·4) versus balloon angioplasty, and -31·8% (-44·8 to -18·6) versus rotablation. DCB were ranked as the second most effective treatment, but without significant differences from sirolimus-eluting (-0·2% [95% CI -6·2 to 5·6]) or paclitaxel-eluting (-1·2% [-6·4 to 4·2]) stents. INTERPRETATION These findings suggest that two strategies should be considered for treatment of any type of coronary ISR: PCI with everolimus-eluting stents because of the best angiographic and clinical outcomes, and DCB because of its ability to provide favourable results without adding a new stent layer. FUNDING None.

The Importance of Patency in Patients with Critical Limb Ischemia Undergoing Endovascular Revascularization for Infrapopliteal Arterial Disease.

Critical limb ischemia (CLI) represents the most severe form of peripheral arterial disease (PAD) and frequently occurs in medically frail patients. CLI patients frequently exhibit multi-segmental PAD commonly including the tibial arterial segment. Endovascular therapy has been established as first-line revascularization strategy for most CLI patients. Restenosis was reported to occur in up to more than two-thirds of CLI patients undergoing angioplasty of complex tibial arterial obstructions. Nevertheless, favorable clinical outcomes were observed for infrapopliteal angioplasty when compared with bypass surgery, despite higher patency rates for the latter. Based on these observations, infrapopliteal patency was considered to be only of secondary importance upon clinical outcomes in CLI patients. In contrast to these earlier observations, however, recent findings from two randomized clinical trials indicate that infrapopliteal patency does impact on clinical outcomes in CLI patients. The purpose of the present manuscript is to provide a critical reappraisal of the present literature on the clinical importance of tibial arterial patency in CLI patients undergoing endovascular revascularization and to discuss utility and limitations of currently available anti-restenosis technologies.

Perspectives on the 2014 ESC/EACTS Guidelines on Myocardial Revascularization: Fifty Years of Revascularization: Where Are We and Where Are We Heading?

The joint European Society of Cardiology and European Association of Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization collect and summarize the evidence regarding decision-making, diagnostics, and therapeutics in various clinical scenarios of coronary artery disease, including elective, urgent, and emergency settings. The 2014 document updates and extends the effort started in 2010, year of the first edition of these guidelines. Importantly, this latest edition provides a systematic review of all randomized clinical trials performed since 1980, comparing different strategies of myocardial revascularization, including coronary artery bypass graft (CABG), balloon angioplasty, percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and first- and second-generation drug-eluting stents (DES). This review aims to highlight the most relevant novelties introduced by the 2014 edition of the ESC/EACTS myocardial revascularization guidelines as compared with the previous edition and to describe similarities and differences with the American societies' guidelines.

A double-blind randomised study to evaluate the efficacy and safety of bindarit in preventing coronary stent restenosis.

AIMS Bindarit (BND) is a selective inhibitor of monocyte chemotactic protein-1 (MCP-1/CCL2), which plays an important role in generating intimal hyperplasia. Our aim was to explore the efficacy and safety of bindarit in preventing restenosis following percutaneous coronary intervention. METHODS AND RESULTS A phase II, double-blind, multicentre randomised trial included 148 patients randomised into three arms (BND 600 mg, n=48; BND 1,200 mg, n=49; PLB, n=51). Bindarit was given following PCI and continued for 180 days. Monthly clinical follow-up and six-month coronary angiography were conducted. The primary endpoint was in-segment late loss; the main secondary endpoints were in-stent late loss and major adverse cardiovascular events. Efficacy analysis was carried out on two populations, ITT and PP. There were no significant differences in the baseline characteristics among the three treatment groups. In-segment and in-stent late loss at six months in BND 600, BND 1,200 and PLB were: (ITT 0.54 vs. 0.52 vs. 0.72; p=0.21), (PP 0.46 vs. 0.53 vs. 0.72; p=0.12) and (ITT 0.74 vs. 0.74 vs. 1.05; p=0.01), (PP 0.66 vs. 0.73 vs. 1.06; p=0.003), respectively. The MACE rates at nine months among treatment groups were 20.8% vs. 28.6% vs. 25.5% (p=0.54), respectively. CONCLUSIONS This was a negative study with the primary endpoint not being met. However, significant reduction in the in-stent late loss suggests that bindarit probably exerts a favourable action on the vessel wall following angioplasty. Bindarit was well tolerated with a compliance rate of over 90%. A larger study utilising a loading dose and targeting a specific patient cohort may demonstrate more significant results.

Endovascular stent reconstruction of a chronic total occlusion of the inferior vena cava using bidirectional wire access and a balloon puncture by a re-entry device.

Venous angioplasty with stenting of iliac veins is an important treatment option for patients suffering from post-thrombotic syndrome due to chronic venous obstruction. Interventional treatment of a chronically occluded vena cava, however, is challenging and often associated with failure. We describe a case of a chronic total occlusion of the entire inferior vena cava that was successfully recanalized using bidirectional wire access and a balloon puncture by a re-entry catheter to establish patency of the inferior vena cava.

An analysis of IN.PACT DEEP randomized trial on the limitations of the societal guidelines-recommended hemodynamic parameters to diagnose critical limb ischemia.

OBJECTIVE Recent small single-center data indicate that the current hemodynamic parameters used to diagnose critical limb ischemia are insensitive. We investigated the validity of the societal guidelines-recommended hemodynamic parameters against core laboratory-adjudicated angiographic data from the multicenter IN.PACT DEEP (RandomIzed AmPhirion DEEP DEB vs StAndard PTA for the treatment of below the knee Critical limb ischemia) Trial. METHODS Of the 358 patients in the IN.PACT DEEP Trial to assess drug-eluting balloon vs standard balloon angioplasty for infrapopliteal disease, 237 had isolated infrapopliteal disease with an available ankle-brachial index (ABI), and only 40 of the latter had available toe pressure measurements. The associations between ABI, ankle pressure, and toe pressure with tibial runoff, Rutherford category, and plantar arch were examined according to the cutoff points recommended by the societal guidelines. Abnormal tibial runoff was defined as severely stenotic (≥70%) or occluded and scored as one-, two-, or three-vessel disease. A stenotic or occluded plantar arch was considered abnormal. RESULTS Only 14 of 237 patients (6%) had an ABI <0.4. Abnormal ankle pressure, defined as <50 mm Hg if Rutherford category 4 and <70 mm Hg if Rutherford category 5 or 6, was found only in 37 patients (16%). Abnormal toe pressure, defined as <30 mm Hg if Rutherford category 4 and <50 mm Hg if Rutherford category 5 or 6, was found in 24 of 40 patients (60%) with available measurements. Importantly, 29% of these 24 patients had an ABI within normal reference ranges. A univariate multinomial logistic regression found no association between the above hemodynamic parameters and the number of diseased infrapopliteal vessels. However, there was a significant paradoxic association where patients with Rutherford category 6 had higher ABI and ankle pressure than those with Rutherford category 5. Similarly, there was no association between ABI and pedal arch patency. CONCLUSIONS The current recommended hemodynamic parameters fail to identify a significant portion of patients with lower extremity ulcers and angiographically proven severe disease. Toe pressure has better sensitivity and should be considered in all patients with critical limb ischemia.

Thrombolytic therapy for acute myocardial infarction: A cohort study to evaluate a selective approach to invasive diagnosis and therapy. The Corpus Christi Heart Project

Coronary perfusion with thrombolytic therapy and selective reperfusion by percutaneous transluminal coronary angioplasty (PTCA) were examined in the Corpus Christi Heart Project, a population-based surveillance program for hospitalized acute myocardial infarction (MI) patients in a biethnic community of Mexican-Americans (MAs) and non-Hispanic whites (NHWs). Results were based on 250 (12.4%) patients who received thromobolytic therapy in a cohort of 2011 acute MI cases. Out of these 107 (42.8%) underwent PTCA with a mean follow-up of 25 months. There were 186 (74.4%) men and 64 (25.6%) women; 148 (59.2%) were NHWs, 86 (34.4%) were MAs. Thrombolysis and PTCA were performed less frequently in women than in men, and less frequently in MAs than in NHWs.^ According to the coronary reperfusion interventions used, patients were divided in two groups, those that received no-PTCA (57.2%) and the other that underwent PTCA (42.8%) after thrombolysis. The case-fatality rate was higher in no-PTCA patients than in the PTCA (7.7% versus 5.6%), as was mortality at one year (16.2% versus 10.5%). Reperfusion was successful in 48.0% in the entire cohort and (51.4% versus 45.6%) in the PTCA and no-PTCA groups. Mortality in the successful reperfusion patients was 5.0% compared to 22.3% in the unsuccessful reperfusion group (p = 0.00016, 95% CI: 1.98-11.6).^ Cardiac catheterization was performed in 86.4% thrombolytic patients. Severe stenosis ($>$75%) obstruction was present most commonly in the left descending artery (52.8%) and in the right coronary artery (52.8%). The occurrence of adverse in-hospital clinical events was higher in the no-PTCA as compared to the PTCA and catheterized patients with the exception of reperfusion arrythmias (p = 0.140; Fisher's exact test p = 0.129).^ Cox regression analysis was used to study the relationship between selected variables and mortality. Apart from successful reperfusion, age group (p = 0.028, 95% CI: 2.1-12.42), site of acute MI index (p = 0.050) and ejection-fraction (p = 0.052) were predictors of long-term survival. The ejection-fraction in the PTCA group was higher than (median 78% versus 53%) in the no-PTCA group. Assessed by logistic regression analysis history of high cholesterol ($>$200mg/dl) and diabetes mellites did have significant prognostic value (p = 0.0233; p = 0.0318) in long-term survival irrespective of treatment status.^ In conclusion, the results of this study support the idea that the use of PTCA as a selective intervention following thrombolysis improves survival of patients with acute MI. The use of PTCA in this setting appears to be safe. However, we can not exclude the possibility that some of these results may have occurred due to the exclusion from PTCA of high risk patients (selection bias). ^

The use of invasive myocardial revascularization procedures following myocardial infarction and the effectiveness of these procedures in the biethnic community of Nueces County, Texas, 1988--1991

High levels of poverty and unemployment, and low levels of health insurance coverage may pose barriers to obtaining cardiac care by Mexican Americans. We undertook this study to investigate differences in the use of invasive myocardial revascularization procedures received within the 4-month period following hospitalization for a myocardial infarction (MI) between Mexican Americans and non-Hispanic whites in the Corpus Christi Heart Project (CCHP). The CCHP is a population-based surveillance program for hospitalized MI, percutaneous transluminal coronary angioplasty (PTCA), and aortocoronary bypass surgery (ACBS). Medical record data were available for 1706 patients identified over a three-year period. Mexican Americans had significantly lower rates of receiving a PTCA following MI than non-Hispanic Whites (RR: 0.56, 95% CI: 0.44-0.70). No meaningful ethnic difference was seen in the rates of ACBS use. History of PTCA use appeared to interact with ethnicity. Among patients without a history of PTCA use, Mexican Americans were less likely to receive a PTCA than non-Hispanic whites (RR: 0.59; 95% CI: 0.46-0.76). Among patients with a history of PTCA use, however, Mexican Americans were more likely to receive a PTCA than non-Hispanic whites (RR: 1.47; 95% CI: 0.75-2.87).^ Differences in the effectiveness of a first-time PTCA and first-time ACBS between Mexican Americans and non-Hispanic whites in the CCHP were also investigated. Mexican Americans were more likely to receive a 2nd PTCA (RR: 1.56, 95% CI: 1.11-2.17) and suffer a subsequent MI (RR: 1.42, 95% CI: 1.03-1.96) following a first-time PTCA than non-Hispanic whites. No meaningful ethnic differences were found in the rates of death and rates of ACBS following a first-time PTCA. Also, no significant ethnic differences were found in the rates of any of the events following a first-time ACBS. After adjusting for potential demographic, socioeconomic, clinical and angiographic confounders using Cox regression analysis, Mexican Americans were still more likely to receive a 2nd PTCA (HR: 1.38; 95% CI: 0.99-1.93) following a first-time PTCA than non-Hispanic whites. A significant difference in the rates of a subsequent MI following a first-time PTCA persisted (HR: 1.39, 95% CI: 1.01-1.93). (Abstract shortened by UMI.) ^

Estudio del flujo sanguíneo para diferentes técnicas de implantación de stents en bifurcaciones coronarias

Las enfermedades arteriales vienen presididas por la aterosclerosis, que es un proceso crónico de degeneración, que evoluciona hacia la obstrucción de la luz arterial. La pared de la arteria se engrosa debido al depósito de elementos grasos tales como el colesterol. Los stents intraluminales son diminutas estructuras tubulares autoexpandibles de malla de metal, que se colocan dentro de la arteria coronaria después de una angioplastia con balón para prevenir el cierre de dicha arteria. A pesar de estar diseñados para ser compatibles con el tejido humano, a menudo se da una reacción en cadena de consecuencias indeseables. La reestenosis intra-stent es un problema creciente debido al importante incremento que se ha producido en la utilización del stent intracoronario como forma de revascularización percutánea. Se habla de una incidencia global del 28%, siendo la causa principal de su aparición la proliferación neointimal a través de una compleja cascada de sucesos que pueden tardar meses en desarrollarse. Una de las reacciones más importantes es la trombosis o la formación de una fina capa de coágulo como respuesta a la presencia de un material extraño. Este proceso es multifactorial, y en él intervienen la regresión de la pared como consecuencia del estiramiento previo, la denudación endotelial, lo que permite la agregación plaquetaria, la proliferación neointimal, lo que facilita a los receptores de membrana desencadenar un proceso de agregación posterior y, por último, el remodelado negativo inadecuado de la pared, lo que produce pérdida de luz arterial. Se ha observado frecuentemente que el depósito de ateroma en la pared arterial está relacionado con el valor de los esfuerzos cortantes en la misma. Hay mayores probabilidades de engrosamiento de la pared en las zonas donde son bajos los esfuerzos cortantes, quizá por el mayor tiempo de residencia de las partículas circulantes por el torrente sanguíneo. Si nos centramos en la afirmación anterior, el siguiente paso sería buscar las zonas susceptibles de presentar un valor bajo de dichos esfuerzos. Las zonas potencialmente peligrosas son los codos y bifurcaciones, entre otras. Nos hemos centrado en una bifurcación coronaria, ya que los patrones de flujo que se suelen presentar, tales como recirculación y desprendimiento de vórtices están íntimamente relacionados con las técnicas de implantación de stents en esta zona. Proyectamos nuestros esfuerzos en el estudio de dos técnicas de implante, utilizando un único stent y una tercera a través de una configuración de culotte con el uso de dos stents. El primer caso trata de una bifurcación con un único stent en la rama principal cuyos struts cierran el orificio lateral que da salida a la rama secundaria de la bifurcación, es decir sería un stent sin orificio. El segundo consiste en un único stent también, pero con la diferencia de que éste presenta un orificio de comunicación con la rama lateral. Todas estas técnicas se aplicaron a bifurcaciones de 45º y de 90º. Introdujimos las geometrías -una vez confeccionadas con el código comercial Gambit- en el programa Ansys-Fluent contemplando régimen estacionario. Los resultados obtenidos fueron cotejados con los experimentales, que se realizaron paralelamente, con el fin de corroborarlos. Una vez validados, el estudio computacional ya contó con la fiabilidad suficiente como para abordar el régimen no estacionario, tanto en la versión de reposo como en la de ejercicio –hiperemia- El comportamiento reológico de la sangre para régimen no estacionario en estado de reposo es otra de las tareas abordadas, realizando una comparativa de los modelos Newtoniano, Carreau y Ley de Potencias. Finalmente, en una última etapa, debido a la reciente incursión de los stents diseñados específicamente frente a los convencionales, se aborda el comportamiento hemodinámico de los mismos. Concretamente, se comparó el patrón de flujo en un modelo de bifurcación coronaria con los nuevos stents (Stentys) y los convencionales. Se estudiaron cuatro modelos, a saber, stent simple en la rama principal, stent simple en la rama secundaria, culotte desplegando el primer stent en la rama principal y culotte desplegando el primer stent en la rama secundaria. La bifurcación estudiada presenta un ángulo de apertura de 45º y la relación de diámetros de las ramas hija se ajustaron de acuerdo a la ley de Finet. Se recogieron resultados experimentales en el laboratorio y se corrieron simulaciones numéricas con Ansys Fluent paralelamente. Las magnitudes que se tuvieron en cuenta con el fin de ubicar las regiones potencialmente ateroscleróticas fueron los esfuerzos cortantes, vorticidad y caída de presión. ABSTRACT Nowadays, restenosis after percutaneous dilation is the major drawback of coronary angioplasty. It represents a special form of atherosclerosis due to the healing process secondary to extensive vessel trauma induced after intracoronary balloon inflation. The use of coronary stents may decrease the incidence of this phenomenon. Unfortunately, intra-stent restenosis still occurs in 20-30% of the cases following the stent implantation. Most experiments suggest a correlation between low wall shear stress and wall thickness. The preferential locations for the atherosclerotic plaque are bifurcations. The objective of this work is to analyze the local hemodynamic changes caused in a coronary bifurcation by three different stenting techniques: simple stenting of the main vessel, simple stenting of the main vessel with kissing balloon in the side branch and culotte. To carry out this study an idealized geometry of a coronary bifurcation is used, and two bifurcation angles, 45º and 90º, are chosen as representative of the wide variety of real configurations. Both numerical simulations and experimental measurements are performed. First, steady simulations are carried out with the commercial code Ansys-Fluent, then, experimental measurements with PIV (Particle Image Velocimetry), obtained in the laboratory, are used to validate the numerical simulations. The steady computational simulations show a good overall agreement with the experimental data. Then, pulsatile flow is considered to take into account the transient effects. The time averaged wall shear stress, oscillatory shear index and pressure drop obtained numerically are used to compare the behavior of the stenting techniques. In a second step, the rheologic behavior of blood was considered comparing Newtonian, Carreau and Power Law models. Finally, as a result of previous investigations with conventional stents and after the recent emergence of several devices specifically designed for coronary bifurcations angioplasty, the hemodynamic performance of these new devices (Stentys) was compared to conventional ones and techniques in a coronary bifurcation model. Four different stenting techniques: simple stenting of the main vessel, simple stenting of the side vessel, culotte deploying the first stent in the main vessel and culotte deploying the first stent in the side vessel have been considered. To carry out this study an idealized geometry of a coronary bifurcation is used. A 45 degrees bifurcation angle is considered and the daughter branches diameters are obtained according to the Finet law. Both experiments in the laboratory and numerical simulations were used , focusing on important factors for the atherosclerosis development, like the wall shear stress, the oscillation shear index, the pressure loss and the vorticity.

A study of the mechanical behaviour of the human aortic artery by means of non-linear finite element models

En la presente tesis desarrollamos una estrategia para la simulación numérica del comportamiento mecánico de la aorta humana usando modelos de elementos finitos no lineales. Prestamos especial atención a tres aspectos claves relacionados con la biomecánica de los tejidos blandos. Primero, el análisis del comportamiento anisótropo característico de los tejidos blandos debido a las familias de fibras de colágeno. Segundo, el análisis del ablandamiento presentado por los vasos sanguíneos cuando estos soportan cargas fuera del rango de funcionamiento fisiológico. Y finalmente, la inclusión de las tensiones residuales en las simulaciones en concordancia con el experimento de apertura de ángulo. El análisis del daño se aborda mediante dos aproximaciones diferentes. En la primera aproximación se presenta una formulación de daño local con regularización. Esta formulación tiene dos ingredientes principales. Por una parte, usa los principios de la teoría de la fisura difusa para garantizar la objetividad de los resultados con diferentes mallas. Por otra parte, usa el modelo bidimensional de Hodge-Petruska para describir el comportamiento mesoscópico de los fibriles. Partiendo de este modelo mesoscópico, las propiedades macroscópicas de las fibras de colágeno son obtenidas a través de un proceso de homogenización. En la segunda aproximación se presenta un modelo de daño no-local enriquecido con el gradiente de la variable de daño. El modelo se construye a partir del enriquecimiento de la función de energía con un término que contiene el gradiente material de la variable de daño no-local. La inclusión de este término asegura una regularización implícita de la implementación por elementos finitos, dando lugar a resultados de las simulaciones que no dependen de la malla. La aplicabilidad de este último modelo a problemas de biomecánica se estudia por medio de una simulación de un procedimiento quirúrgico típico conocido como angioplastia de balón. In the present thesis we develop a framework for the numerical simulation of the mechanical behaviour of the human aorta using non-linear finite element models. Special attention is paid to three key aspects related to the biomechanics of soft tissues. First, the modelling of the characteristic anisotropic behaviour of the softue due to the collagen fibre families. Secondly, the modelling of damage-related softening that blood vessels exhibit when subjected to loads beyond their physiological range. And finally, the inclusion of the residual stresses in the simulations in accordance with the opening-angle experiment The modelling of damage is addressed with two major and different approaches. In the first approach a continuum local damage formulation with regularisation is presented. This formulation has two principal ingredients. On the one hand, it makes use of the principles of the smeared crack theory to avoid the mesh size dependence of the structural response in softening. On the other hand, it uses a Hodge-Petruska bidimensional model to describe the fibrils as staggered arrays of tropocollagen molecules, and from this mesoscopic model the macroscopic material properties of the collagen fibres are obtained using an homogenisation process. In the second approach a non-local gradient-enhanced damage formulation is introduced. The model is built around the enhancement of the free energy function by means of a term that contains the referential gradient of the non-local damage variable. The inclusion of this term ensures an implicit regularisation of the finite element implementation, yielding mesh-objective results of the simulations. The applicability of the later model to biomechanically-related problems is studied by means of the simulation of a typical surgical procedure, namely, the balloon angioplasty.