Author Correction: Comparison of 1D and 3D Models for the Estimation of Fractional Flow Reserve.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Comparison of 1D and 3D Models for the Estimation of Fractional Flow Reserve.

In this work we propose to validate the predictive capabilities of one-dimensional (1D) blood flow models with full three-dimensional (3D) models in the context of patient-specific coronary hemodynamics in hyperemic conditions. Such conditions mimic the state of coronary circulation during the acquisition of the Fractional Flow Reserve (FFR) index. Demonstrating that 1D models accurately reproduce FFR estimates obtained with 3D models has implications in the approach to computationally estimate FFR. To this end, a sample of 20 patients was employed from which 29 3D geometries of arterial trees were constructed, 9 obtained from coronary computed tomography angiography (CCTA) and 20 from intra-vascular ultrasound (IVUS). For each 3D arterial model, a 1D counterpart was generated. The same outflow and inlet pressure boundary conditions were applied to both (3D and 1D) models. In the 1D setting, pressure losses at stenoses and bifurcations were accounted for through specific lumped models. Comparisons between 1D models (FFR1D) and 3D models (FFR3D) were performed in terms of predicted FFR value. Compared to FFR3D, FFR1D resulted with a difference of 0.00 ± 0.03 and overall predictive capability AUC, Acc, Spe, Sen, PPV and NPV of 0.97, 0.98, 0.90, 0.99, 0.82, and 0.99, with an FFR threshold of 0.8. We conclude that inexpensive FFR1D simulations can be reliably used as a surrogate of demanding FFR3D computations.

Avaliação clínica inicial de novo balão farmacológico com sirolimus e nano partículas no tratamento de lesões reestenóticas / Initial clinical evaluation of a new sirolimus and nanoparticle pharmacological balloon in the treatment of restenosis lesions

INTRODUÇÃO: Recentemente, o conceito dos chamados balões farmacológicos tem sido testado no tratamento da reestenose intra stent, como uma alternativa de tratamento sem implante adicional de outra camada de metal no sítio previamente tratado. Ainda que os balões farmacológicos com paclitaxel tenham se mostrado eficazes para esta finalidade, esta tecnologia ainda apresenta alguns desafios: o paclitaxel é sabidamente menos efetivo e mais tóxico que outros fármacos anti-proliferativos, em especial quando comparado ao sirolimus e seus análogos/derivados. No presente estudo avaliamos um novo balão-farmacológico (Magic Touch), que utiliza sirolimus na dose de 1,27µg/mm2 , depositado em solução excipiente (nano partícula), na concentração de 1:1. MÉTODOS: Estudo prospectivo, multicêntrico, de braço único, incluindo pacientes com reestenose tanto de stents nãofarmacológicos como farmacológicos, tratados com balão Magic Touch. Não foram incluídas reestenoses do tipo oclusiva. Os pacientes foram submetidos a avaliação angiográfica e com ultrassom (USIC) aos seis meses. O desfecho primário foi a avaliação do grau de supressão neointinamal aos seis meses pela angiografia (perda luminal) e USIC (% de obstrução luminal). RESULTADO: Um total de 17 pacientes foram incluídos, sendo a maioria do sexo masculino (59%), com média de idade de 58 anos e com 60% de diabéticos. Metade da população tratada apresentava reestenose de stents farmacológicos e em 62% dos casos a reestenose era do tipo difusa/proliferativa. Sucesso angiográfico foi obtido em 100% dos casos. Aos 6 meses, a mediana da perda luminal tardia intra stent foi de 0,21mm [0,07; 0,51] ao passo que ao USIC, o% de obstrução luminal foi de 20% [18; 24]. Do ponto de vista clínico, ocorreu apenas um óbito, de causa não cardíaca. CONCLUSÃO: Neste estudo inicial em humanos, o balão farmacológico com sirolimus e nano partículas mostrou-se eficaz em reduzir a proliferação neointimal em pacientes com reestenose prévia de stents não-farmacológicos e/ou farmacológicos. (AU)

A head-to-head comparison between CT- and IVUS-derived coronary blood flow models.

The goal of this work is to compare coronary hemodynamics as predicted by computational blood flow models derived from two imaging modalities: coronary computed tomography angiography (CCTA) and intravascular ultrasound integrated with angiography (IVUS). Criteria to define boundary conditions are proposed to overcome the dissimilar anatomical definition delivered by both modalities. The strategy to define boundary conditions is novel in the present context, and naturally accounts for the flow redistribution induced by the resistance of coronary vessels. Hyperemic conditions are assumed to assess model predictions under stressed hemodynamic environments similar to those encountered in Fractional Flow Reserve (FFR) calculations. As results, it was found that CCTA models predict larger pressure drops, higher average blood velocity and smaller FFR. Concerning the flow rate at distal locations in the major vessels of interest, it was found that CCTA predicted smaller flow than IVUS, which is a consequence of a larger sensitivity of CCTA models to coronary steal phenomena. Comparisons to in-vivo measurements of FFR are shown.

A computational framework to characterize and compare the geometry of coronary networks.

This work presents a computational framework to perform a systematic and comprehensive assessment of the morphometry of coronary arteries from in vivo medical images. The methodology embraces image segmentation, arterial vessel representation, characterization and comparison, data storage, and finally analysis. Validation is performed using a sample of 48 patients. Data mining of morphometric information of several coronary arteries is presented. Results agree to medical reports in terms of basic geometric and anatomical variables. Concerning geometric descriptors, inter-artery and intra-artery correlations are studied. Data reported here can be useful for the construction and setup of blood flow models of the coronary circulation. Finally, as an application example, similarity criterion to assess vasculature likelihood based on geometric features is presented and used to test geometric similarity among sibling patients. Results indicate that likelihood, measured through geometric descriptors, is stronger between siblings compared with non-relative patients. Copyright © 2016 John Wiley & Sons, Ltd.

Randomised comparison of the efficacy and safety of a novelDES with biodegradable polymer and cobalt-chromium alloy -Inspiron I trial

Aims: The efficacy of a novel drug eluting stents with biodegradable polymer andcobalt-chromium alloy should be tested in the context of randomised trials, evenwhen using drugs known to be effective, such as sirolimus. The objective of thepresent study was to evaluate the safety and efficacy of a novel formulation of asirolimus-eluting stent with biodegradable polymer and cobalt-chromium alloyagainst a stent with the same metallic structure but without polymer coating or drugelution.Methods and results: The INSPIRON-I trial is a multicenter 2-arm randomisedtrial, conducted in 4 Brazilian institutions, which included 58 patients allocated forthe Inspiron sirolimus-eluting stent or the Cronus bare metal stent in a 2:1 ratio.Patients had de novo coronary lesions in native vessels with a diameter between2.5 and 3.5 mm, amenable for treatment with a single stent of 19 mm or less in length. The primary objective was to compare the in-stent late loss at 6 months of the sirolimus-eluting versus the control bare metal stent. Important secondary objectives included the comparison of major adverse cardiac events (MACE) ofdeath, myocardial infarction and target lesion revascularisation at 12 months. The study randomised 58 patients, 39 in the Inspiron group and 19 in the Cronusgroup. The great majority of the patients included had stable angina (76%).Baseline clinical and angiographic characteristics from both groups were similar, and 55.6% of the lesions were B2/C. The angiographic restudy at 6 months showed that percent diameter stenosis was significantly lower in the Inspiron group (15.8% vs. 38.7%, respectively; p=0.03), as well as late lumen loss (0.18 vs. 0.67 mm; p=0.009). Binary restenosis was also lower for Inspiron group, but without statistical difference (p=0.42)...

One year cost effectiveness of sirolimus eluting stents compared with bare metal stents in the treatment of single native de novo coronary lesions: an analysis from the RAVEL trial.

OBJECTIVE: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. DESIGN: Multicentre, double blind, randomised trial. SETTING: Percutaneous coronary intervention for single de novo coronary lesions. PATIENTS: 238 patients with stable or unstable angina. INTERVENTIONS: Randomisation to sirolimus eluting stent or bare stent implantation. MAIN OUTCOME MEASURES: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. RESULTS: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the additional one year costs at 166. CONCLUSIONS: The one year data from RAVEL suggest an attractive balance between costs and effects for sirolimus eluting stents in the treatment of single native de novo coronary lesions. The cost effectiveness of drug eluting stents in more complex lesion subsets remains to be determined.

Drug-eluting stents: from randomized trials to the real world.

Drug-eluting stents have been developed to prevent in-stent restenosis following percutaneous coronary revascularization. In a number of randomized trials, polymer-coated sirolimus- and paclitaxel-eluting stents have been proven to markedly reduce the incidence of angiographic restenosis and repeat revascularization when compared to bare metal stents. Effectiveness of sirolimus-eluting stents in the prevention of restenosis has been confirmed in many subsets of patients and lesions not included in randomized trials, such as in-stent restenosis, chronic total occlusion, acute myocardial infarction, and others. Very promising data in the real world are emerging for utilization of paclitaxel-eluting stents as well. Other drug-eluting stents gave less brilliant results or even true failures, whilst a number of new drugs and stent platforms are under clinical or preclinical evaluation. In this review we describe the main clinical trials on drug-eluting stents, and the most recent informations derived from observational studies and registries. Moreover, preliminary results on new drug-eluting stents are summarized.

Beneficial effects of fluvastatin following percutaneous coronary intervention in patients with unstable and stable angina: results from the Lescol intervention prevention study (LIPS).

AIMS: To investigate the effect on risk of major adverse cardiac events (MACE) of lipid lowering treatment with fluvastatin 80 mg/day after a first percutaneous coronary intervention in patients with stable and unstable angina. METHOD AND RESULTS: This prespecified subgroup analysis of the LIPS (Lescol intervention prevention study) analysed 1658 patients with documented diagnosis; 824 had unstable angina (417 randomly assigned to fluvastatin, 407 to placebo) and 834 had stable angina (including silent ischaemia; fluvastatin, 418; placebo, 416). Median follow up was 3.9 years. There was no significant effect of anginal status on long term risk of MACE. Fluvastatin treatment reduced the risk of MACE by 28% compared with placebo (p = 0.03) among patients with unstable angina, with no difference between patients with stable and patients with unstable angina (relative risk 1.07, 95% confidence interval 0.87 to 1.30, p = 0.53). Fluvastatin reduced coronary atherosclerotic events (MACE excluding restenosis) by 36% (p = 0.006) among patients with unstable angina and 31% (p = 0.02) among patients with stable angina. Fluvastatin caused similar reductions in total cholesterol and low density lipoprotein cholesterol concentrations in both patient groups. CONCLUSION: Treatment with fluvastatin 80 mg/day produced significant reductions in MACE and coronary atherosclerotic events after percutaneous coronary intervention in patients with average cholesterol concentrations. The beneficial effects of fluvastatin are observed in patients with unstable or stable angina alike.

Routine sirolimus eluting stent implantation for unselected in-stent restenosis: insights from the rapamycin eluting stent evaluated at Rotterdam Cardiology Hospital (RESEARCH) registry.

OBJECTIVE: To assess the effectiveness of routine sirolimus eluting stent (SES) implantation for unselected patients with in-stent restenosis and to provide preliminary information about the angiographic outcome for lesion subgroups and for different in-stent restenosis patterns. DESIGN: Prospective, single centre registry. SETTING: Tertiary referral centre. PATIENTS: 44 consecutive patients (53 lesions) without previous brachytherapy who were treated with SES for in-stent restenosis were evaluated. Routine angiographic follow up was obtained at six months and the incidence of major adverse cardiovascular events was evaluated. RESULTS: At baseline, 42% of the lesions were focal, 21% diffuse, 26% proliferative, and 11% total occlusions. Small vessel size (reference diameter < or = 2.5 mm) was present in 49%, long lesions (> 20 mm) in 30%, treatment of bypass grafts in 13%, and bifurcation stenting in 18%. At follow up, post-SES restenosis was observed in 14.6%. No restenosis was observed in focal lesions. For more complex lesions, restenosis rates ranged from 20-25%. At the one year follow up, the incidence of death was 0, myocardial infarction 4.7% (n = 2), and target lesion revascularisation 16.3% (n = 7). The target lesion was revascularised because of restenosis in 11.6% (n = 5). CONCLUSIONS: Routine SES implantation is highly effective for focal in-stent restenosis and appears to be a promising strategy for more complex patterns of restenosis.

Renoprotective effect of high periprocedural doses of oral N-acetylcysteine in patients scheduled to undergo a same-day angiography

BACKGROUND: Few studies that have assessed the effect of abbreviated oral N-acetylcysteine (NAC) regimens in radiocontrast-induced nephropathy (RCIN) yield mixed results. OBJECTIVE: To evaluate the renoprotective effect of high periprocedural oral doses (HPOD) of NAC in patients with chronic renal impairment undergoing a same-day angiography. METHODS: Sixty one patients with renal impaired function scheduled to undergo a same-day angiography were randomly assigned to NAC 1200 mg orally 3 hours before and 3 after the procedure, or a placebo. All patients received 0.9% saline intravenous. RCIN was defined as an increase in SCC > 0.5 mg/dl 48 hours after the procedure. RESULTS: The mean baseline SCC for all patients was 1.44 +/- 0.42 mg/dl. A significant difference in SCC change at 48 hours after the angiography was found (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P = 0.04). RCIN occurred in 1 (3%) patient of NAC group and in 2 (7.1%) patients of placebo group (P = 0.59). Adverse effects were similar in both groups. CONCLUSIONS: In patients with mild renal impairment patients undergoing angiographic procedures, HPOD of NAC were more effective than placebo in preventing SCC change 48 hours. A non significant benefit in RCIN incidence was found.

Los escasos estudios que han evaluados los efectos de regimenes abreviados de Nacetilcisteína (NAC) oral en la nefropatía por contraste (NC) han encontrado resultados contrapuestos. OBJETIVO: Evaluar el efecto renoprotector de altas dosis orales periprocedimiento (ADOP) de NAC en pacientes con insuficiencia renal con angiografía programada el mismo día. MATERIAL y METODOS: Sesenta y un pacientes con insuficiencia renal y angiografía programada para el mismo día fueron asignados aleatoriamente a 1200 mg de NAC 3 horas previas y 3 horas posteriores al cateterismo o un placebo. Todos los pacientes recibieron hidratación endovenosa con solución salina al 0.9%. La NC se definió como el aumento en la creatinina sérica (CS) > 0.5 mg/dl a las 48 horas del procedimiento. RESULTADOS: La CS media en todos los pacientes fue 1.44: t 0.42 mg/dl. Se encontró una diferencia significativa entre ambos grupos en el cambio de CS a las 48 horas de la angiografía (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P=0.04). La NC se presentó en 1 (3%) paciente del grupo NAC y en 2 (7.1 %) pacientes del grupo placebo (P=0.59). Los efectos adversos fueron similares en ambos grupos. CONCLUSION: En pacientes con insuficiencia renal leve sometidos a angiografía en el mismo día, las ADOP de NAC fueron más efectivas que el placebo en la prevención del cambio de CS a las 48 horas del procedimiento. Se encontró un beneficio no significativo en la incidencia de NC.

Renoprotective effect of high periprocedural doses of oral N-acetylcysteine in patients scheduled to undergo a same-day angiography

BACKGROUND: Few studies that have assessed the effect of abbreviated oral N-acetylcysteine (NAC) regimens in radiocontrast-induced nephropathy (RCIN) yield mixed results. OBJECTIVE: To evaluate the renoprotective effect of high periprocedural oral doses (HPOD) of NAC in patients with chronic renal impairment undergoing a same-day angiography. METHODS: Sixty one patients with renal impaired function scheduled to undergo a same-day angiography were randomly assigned to NAC 1200 mg orally 3 hours before and 3 after the procedure, or a placebo. All patients received 0.9% saline intravenous. RCIN was defined as an increase in SCC > 0.5 mg/dl 48 hours after the procedure. RESULTS: The mean baseline SCC for all patients was 1.44 +/- 0.42 mg/dl. A significant difference in SCC change at 48 hours after the angiography was found (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P = 0.04). RCIN occurred in 1 (3%) patient of NAC group and in 2 (7.1%) patients of placebo group (P = 0.59). Adverse effects were similar in both groups. CONCLUSIONS: In patients with mild renal impairment patients undergoing angiographic procedures, HPOD of NAC were more effective than placebo in preventing SCC change 48 hours. A non significant benefit in RCIN incidence was found.(AU)

Los escasos estudios que han evaluados los efectos de regimenes abreviados de Nacetilcisteína (NAC) oral en la nefropatía por contraste (NC) han encontrado resultados contrapuestos. OBJETIVO: Evaluar el efecto renoprotector de altas dosis orales periprocedimiento (ADOP) de NAC en pacientes con insuficiencia renal con angiografía programada el mismo día. MATERIAL y METODOS: Sesenta y un pacientes con insuficiencia renal y angiografía programada para el mismo día fueron asignados aleatoriamente a 1200 mg de NAC 3 horas previas y 3 horas posteriores al cateterismo o un placebo. Todos los pacientes recibieron hidratación endovenosa con solución salina al 0.9%. La NC se definió como el aumento en la creatinina sérica (CS) > 0.5 mg/dl a las 48 horas del procedimiento. RESULTADOS: La CS media en todos los pacientes fue 1.44: t 0.42 mg/dl. Se encontró una diferencia significativa entre ambos grupos en el cambio de CS a las 48 horas de la angiografía (-0.07 mg/dl NAC, 0.09 mg/dl placebo, P=0.04). La NC se presentó en 1 (3%) paciente del grupo NAC y en 2 (7.1 %) pacientes del grupo placebo (P=0.59). Los efectos adversos fueron similares en ambos grupos. CONCLUSION: En pacientes con insuficiencia renal leve sometidos a angiografía en el mismo día, las ADOP de NAC fueron más efectivas que el placebo en la prevención del cambio de CS a las 48 horas del procedimiento. Se encontró un beneficio no significativo en la incidencia de NC.(AU)

Sirolimus-eluting stents for the treatment of in-stent restenosis.

The treatment of in-stent restenosis (ISR) remains one of the major therapeutic challenge for the interventional cardiologist. All percutaneous mechanical approaches have shown disappointing results and the recurrence of ISR was reported to be unacceptably high. Currently, the only proven effective therapy available for the treatment of ISR, at least for the most complex lesions, is vascular brachytherapy. However, this therapy is limited by potential side effects and logistic requirements. The introduction of drug-eluting stents, that carry and release antiproliferative agents, have demonstrated to virtually eliminate ISR in de novo lesions. In the light of this promising results for de novo lesions, sirolimus-eluting stents (SES) were recently used for the treatment of ISR in 2 pilot studies. In Sao Paulo, 25 patients with ISR treated with SES (1.4 stent per lesion) presented 4% ISR and no clinical events at 1 year. In Rotterdam, 16 patients with severe ISR were treated with 26 SES. Intravascular ultrasound evaluation demonstrated successful inhibition of neointimal hyperplasia with 1.1% volume obstruction of the stent, which is similar to the Sao Paulo series (0.8%). At 9 months clinical follow-up, 3 patients had experienced 4 major adverse cardiac events (2 deaths and 1 acute myocardial infarction necessitating repeat target vessel angioplasty). With the results presently available, SES implantation can be considered safe and potentially efficacious in the treatment of ISR. However, multicenter, long-term randomized studies are warranted in order to evaluate this new treatment concept.

Coronary artery bypass surgery and percutaneous transluminal coronary angioplasty in patients with multivessel disease.

Since its introduction in the early 1970s, coronary artery bypass grafting (CABG) surgery has been proven to relief anginal symptoms in patients with severe myocardial ischemia. Percutaneous coronary intervention (PCI) was introduced in clinical practice at the end of the 1970s and this treatment has also been established to be effective. PCI has now surpassed CABG as the most common means for treating coronary artery disease (CAD). However, restenosis remains its Achille's heel. Until the mid-1990s, a coronary reintervention was needed in 35% to 40% of the patients. Since then, interventional techniques and technology have evolved with improved success in more complex and anatomical settings, and restenosis has been now consistently decreased to around 20%. Despite all these improvements, the incidence of restenosis, especially in the 1(st) year, is still an important limitation to PCI. The major determinants of restenosis are elastic recoil, negative vessel remodeling and neointimal proliferation as a response to vessel injury induced by angioplasty devices. The use of conventional stents has provided an efficient method to face the first 2 problems, but neointimal proliferation is not affected by stenting. A new approach consists of using the stent as a drug carrier to the target site in order to inhibit restenosis. The first results of utilization of these fascinating drug-eluting stents (DES) to treat relatively simple lesions are very promising, but further analyses for more complex lesions such as those commonly found in daily practice are needed before any definitive conclusions can be made.

Extrinsic compression of the left main coronary artery by a dilated pulmonary artery: clinical, angiographic, and hemodynamic determinants.

Extrinsic compression of the left main coronary artery (LMC) by the pulmonary artery (PA) is a very unusual and poorly understood entity, usually associated with the presence of adult congenital heart disease. We identified 12 patients (age range, 6 months to 55 years) with LMC stenosis (> or = 50%) presumably secondary to compression by a dilated main PA and related to various forms of heart disease (11 congenital, 1 pulmonary hypertension). In all cases, the main PA was dilated with the main PA/aortic root diameter increased (mean, 2.0; normal value, < or = 1.0), and in all but two, PA pressures were increased (> 30 mm Hg systolic). Left coronary trunk stenosis was usually visualized in only one angiographic view (best seen in 45 degrees left anterior oblique, 30 degrees cranial projection). The LMC also appeared to be inferiorly displaced and in close contact with the left aortic sinus (mean angle between sinus and LMC was 23 degrees +/- 13 degrees, a control group was 70 degrees +/- 15 degrees ). In one patient, surgical correction of the dilated PA was associated with a reduction in LMC stenosis from 85% to < 50% and less inferior left main displacement (from 25 degrees to 50 degrees ). Patients with a dilated main PA may exhibit extrinsic LMC compression leading to significant eccentric narrowing and downward displacement of the LMC. In the presence of significant dilatation of the main PA from any etiology, functional and/or anatomic studies should be performed to exclude significant LM obstruction.