Marcadores genéticos y séricos relacionados con una rápida progresión clínica de la arteriosclerosis coronaria / Serum and genetic markers related to rapid clinical progression of coronary artery disease

Introducción y objetivos: La progresión de la enfermedad coronaria una vez se hace evidente a la clínica tiene una gran variabilidad interindividual. El objetivo es determinar marcadores séricos y genéticos en pacientes con rápida progresión clínica (RPC) de la enfermedad coronaria frente a pacientes con estabilidad clínica mantenida (ECM). Métodos: Estudio retrospectivo de casos (RPC) y controles (ECM) (1:2). Se consideró RPC a los pacientes que precisaron al menos 2 revascularizaciones por progresión de la ateroesclerosis en los 10 años posteriores a una primera angioplastia y ECM a aquellos sin eventos durante el mismo periodo tras la primera angioplastia. Una vez seleccionados, se determinaron los valores séricos, la expresión de ácido ribonucleico mensajero (ARNm) y polimorfismos genéticos de interleucina 6, proteína C reactiva y factor de necrosis tumoral alfa (TNFα) como marcadores de inflamación y proproteína convertasa subtilisina/kexina tipo 9 (PCSK9), receptor de lipoproteínas de baja densidad, proteína 2 de unión a elementos reguladores de esteroles y apolipoproteína B como marcadores aterogénicos. Resultados: Se incluyó a 180 pacientes (58 en RPC y 122 en ECM). Las características basales demográficas, del perfil de riesgo clásico y de la extensión de la enfermedad coronaria fueron comparables. El grupo de RPC presentó valores séricos más altos de interleucina 6 y PCSK9 y mayor expresión de ARNm de TNF. Los alelos de Interleucina-6 rs180075C, de TNF rs3093664 non-G y de PCSK9 rs2483205 T confieren riesgo de RPC (p<0,05 en todos los casos). Un 51,7% de los pacientes del grupo RPC presentaron los tres alelos de riesgo frente al 18% de los pacientes del grupo en ECM (p<0,001). Conclusiones: Se propone la existencia de marcadores genotípicos y fenotípicos asociados con la RPC de enfermedad coronaria y que podrían servir para individualizar la intensidad y el tipo de tratamiento.(AU)

Introduction and objectives: Patients with clinically evident coronary artery disease differ in their rate of progression, which impacts prognosis. We aimed to characterize serum and genetic markers in patients with rapid clinical progression (RCP) of coronary artery disease vs those with long standing stable (LSS) disease. Methods: Retrospective study of cases (RCP) and controls (LSS) (1:2). Patients requiring ≥ 2 revascularizations due to atherosclerotic progression in the 10 years after a first angioplasty were considered to be RCP and those without events during the same period after the first angioplasty were considered to have LSS disease. After patient selection, we analyzed serum values, mRNA expression and genetic polymorphisms of inflammatory markers, including interleukin-6, C-reactive protein, and tumor necrosis factor (TNF)-a, and atherogenic markers consisted of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, sterol regulatory element binding transcription factor 2, and apolipoprotein-B. Results: The study included 180 patients (58 RCP and 122 LSS). Demographic characteristics, classic risk factors and the extent of coronary disease were similar in the 2 groups. Patients with RCP showed higher serum levels of interleukin-6 and PCSK9 and higher TNF mRNA expression. Interleukin-6 rs180075C, TNF rs3093664 non-G and PCSK9 rs2483205 T alleles conferred a risk of RCP (P<.05 in all cases). Among patients with RCP, 51.7% had all 3 risk alleles vs 18% of those with LSS (P<.001). Conclusions: We suggest the existence of specific phenotypic and genotypic markers associated with RCP of coronary artery disease that could help to individualize the type and intensity of treatment.(AU)

First description and validation of a new method for estimating aortic stenosis burden and predicting the functional response to TAVI.

Background: Up to one-fifth of patients continue to have poor quality of life after transcatheter aortic valve implantation (TAVI), with an additional similar proportion not surviving 1 year after the procedure. We aimed to assess the value of a new method based on an integrated analysis of left ventricular outflow tract flow velocity and aortic pressure to predict objective functional improvement and prognosis after TAVI. Methods: In a cohort of consecutive patients undergoing TAVI, flow velocity-pressure integrated analysis was obtained from simultaneous pressure recordings in the ascending aorta and flow velocity recordings in the left ventricular outflow tract by echocardiography. Objective functional improvement 6 months after TAVI was assessed through changes in a 6-min walk test and NT-proBNP levels. A clinical follow-up was conducted at 2 years. Results: Of the 102 patients studied, 82 (80.4%) showed objective functional improvement. The 2-year mortality of these patients was significantly lower (9% vs. 44%, p = 0.001). In multivariate analysis, parameter "(Pressure at Vmax - Pressure at Vo)/Vmax" was found to be an independent predictor for objective improvement. The C-statistic was 0.70 in the overall population and 0.78 in the low-gradient subgroup. All echocardiographic parameters and the valvuloarterial impedance showed a C-statistic of <0.6 for the overall and low-gradient patients. In a validation cohort of 119 patients, the C-statistic was 0.67 for the total cohort and 0.76 for the low-gradient subgroup. Conclusion: This new method allows predicting objective functional improvement after TAVI more precisely than the conventional parameters used to assess the severity of aortic stenosis, particularly in low-gradient patients.

Serum and genetic markers related to rapid clinical progression of coronary artery disease.

INTRODUCTION AND OBJECTIVES: Patients with clinically evident coronary artery disease differ in their rate of progression, which impacts prognosis. We aimed to characterize serum and genetic markers in patients with rapid clinical progression (RCP) of coronary artery disease vs those with long standing stable (LSS) disease. METHODS: Retrospective study of cases (RCP) and controls (LSS) (1:2). Patients requiring ≥ 2 revascularizations due to atherosclerotic progression in the 10 years after a first angioplasty were considered to be RCP and those without events during the same period after the first angioplasty were considered to have LSS disease. After patient selection, we analyzed serum values, mRNA expression and genetic polymorphisms of inflammatory markers, including interleukin-6, C-reactive protein, and tumor necrosis factor (TNF)-a, and atherogenic markers consisted of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, sterol regulatory element binding transcription factor 2, and apolipoprotein-B. RESULTS: The study included 180 patients (58 RCP and 122 LSS). Demographic characteristics, classic risk factors and the extent of coronary disease were similar in the 2 groups. Patients with RCP showed higher serum levels of interleukin-6 and PCSK9 and higher TNF mRNA expression. Interleukin-6 rs180075C, TNF rs3093664 non-G and PCSK9 rs2483205 T alleles conferred a risk of RCP (P<.05 in all cases). Among patients with RCP, 51.7% had all 3 risk alleles vs 18% of those with LSS (P<.001). CONCLUSIONS: We suggest the existence of specific phenotypic and genotypic markers associated with RCP of coronary artery disease that could help to individualize the type and intensity of treatment.

Intraprocedural delayed reassessment of paravalvular regurgitation in TAVR significantly reduces the use of postdilatation.

OBJECTIVES: We sought to investigate the effect of a 15-min delayed intraprocedural reassessment of paravalvular aortic regurgitation (PVR) after an immediate evaluation of posttranscatheter aortic valve replacement (TAVR) on the regurgitation grading and usage of postdilatation. BACKGROUND: PVR after TAVR is associated with poor prognosis, but postdilatation may increase the risk of other complications. METHODS: In a prospective cohort of consecutive patients treated with balloon-expandable valve ES-3 ultra, the degree of PVR was assessed immediately and 15 min after that first evaluation (excluded severe cases), with the indication of postdilatation based on the delayed assessment. As a control group, the previous consecutive series of patients also treated with the same model of valve prosthesis was used. RESULTS: A total of 180 patients were included in the prospective study cohort and 152 in the retrospective control group. In the study group, the immediate PVR assessment showed none-trace 27.5%, mild 52%, moderate 19%, and severe 1.5%, and the delayed re-evaluation graded PVR as none-trace 83%, mild 15.6%, and moderate 1.2% (p < 0.001 as compared to immediate). In the control group, the immediate PVR assessment showed none-trace 33.5%, mild 52%, moderate 13%, and severe 1.5%. The rate of postdilatation was 2.8% in the study group versus 10.5% in the control group (p = 0.006). At discharge, no differences were observed between groups in PVR echocardiographic grading. CONCLUSIONS: A post-TAVR delayed intraprocedural reassessment of the PVR shows a clearly lower degree of regurgitation as compared to immediate evaluation, which significantly decreased the indication of postdilatation.

A new integrative approach to assess aortic stenosis burden and predict objective functional improvement after TAVR.

Background: A non-negligible rate of patients undergoing transcatheter aortic valve replacement (TAVR) do not report symptomatic improvement or even die in the short-midterm. We sought to assess the degree of objective functional recovery after TAVR and its prognostic implications and to develop a predictive model. Methods: In a cohort of patients undergoing TAVR, a prospective evaluation of clinical, anatomical, and physiological parameters was conducted before and after the procedure. These parameters were derived from echocardiography, non-invasive analysis of arterial pulse waves, and cardiac tomography. Objective functional improvement 6 months after TAVR was assessed using a 6-min walk test and nitro-terminal pro-brain natriuretic peptide (NT-proBNP) levels. The derived predictive model was prospectively validated in a different cohort. A clinical follow-up was conducted at 2 years. Results: Among the 212 patients included, objective functional improvement was observed in 169 patients (80%) and subjective improvement in 187 (88%). Patients with objective functional improvement showed a much lower death rate at 2 years (9% vs. 31% p = 0.0002). Independent predictors of improvement were as follows: mean aortic gradient of ≥40 mmHg, augmentation index75 of ≥45%, the posterior wall thickness of ≤12 mm, and absence of atrial fibrillation. A simple integer-based point score was developed (GAPA score), which showed an area under the curve of 0.81 for the overall cohort and 0.78 for the low-gradient subgroup. In a validation cohort of 216 patients, these values were 0.75 and 0.76, respectively. Conclusion: A total of 80% of patients experienced objective functional improvement after TAVR, showing a significantly lower 2-year mortality rate. A predictive score was built that showed a good discriminative performance in overall and low-gradient populations.

Validation study to determine the accuracy of central blood pressure measurement using the SphygmoCor XCEL cuff device in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Central aortic blood pressure could be helpful in the evaluation of patients with aortic stenosis (AS). The SphygmoCor XCEL device estimates central blood pressure (BP) measurement with its easy-to-use, operator-independent procedure. However, this device has not been properly validated against invasive measurement in patients with severe AS. We evaluated the relationship between cuff-brachial BP, transfer function-estimated and invasively measured central aortic pressure in patients with severe AS before and after transcatheter aortic valve replacement (TAVR). Agreement between techniques was analyzed and, according to the ARTERY Society recommendations, the minimum acceptable error was a mean difference ± SD ≤5 ± ≤8 mm Hg. A total of 94 patients with AS undergoing TAVR had simultaneous non-invasive and invasive measurements of central BP before and after the procedure. Before TAVR central systolic BP was in average slightly underestimated, though with wide variability, when using the default calibration of brachial-cuff SBP (mean difference ± SD, -3 ± 15 mm Hg), and after TAVR the degree of underestimation increased (mean difference ± SD, -9 ± 13 mm Hg). The agreement tended to improve for those patients with low aortic gradient stenosis compared to those with high gradient at baseline (mean difference ± SD, -2 ± 11 mm Hg vs. -4 ± 17, respectively, p = .3). The cuff-brachial systolic BP yielded numerically lower degree of agreement and weaker correlation with invasive measurements than SphygmoCor XCEL. In patients with severe AS the SphygmoCor XCEL cuff device, despite showing strong correlation, does not meet the ARTERY Society accuracy criteria for non-invasive measurement of central SBP.

First-in-Man Evaluation of a Sirolimus-Eluting Stent With Abluminal Fluoropolymeric/Triflusal Coating With Ultrathin Struts by OCT at 9 Months' Follow-Up: The PROMETHEUS Study.

OBJECTIVES: We sought to investigate stent healing and neointimal hyperplasia with ihtDEStiny drug-eluting stent (DES) by optical coherence tomography (OCT) examination conducted 9 months after implantation. BACKGROUND: The currently used DES present certain features that have been linked separately to their better performance in terms of efficacy and safety. METHODS: First-in-man, prospective and multicenter study including patients treated with ihtDEStiny stent undergoing OCT examination at 9 months follow up. The ihtDEStiny stent is a sirolimus eluting stent with an oval shape ultrathin struts (68 µm) and an abluminal coating of a fluoropolymer containing the antiplatelet agent triflusal. Primary endpoint was the percentage of obstruction of the in-stent volume by the neointima. RESULTS: In 58 patients (63 lesions) in-stent late lumen loss was 0.11 ± 0.23 mm (95% CI 0.05-0.16) with only in 6% of stents being > 0.5 mm and in-segment binary stenosis was 1.6%. In OCT mean neointima volume obstruction was 10.5 ± 6.9% with a mean neointima thickness of 110.9 ± 89.8 µm. The proportion of uncovered struts was 2.5%, malapposed struts 1.1% and malapposed/uncovered struts 0.7% and no subclinical thrombi detected. Mean incomplete stent apposition area was 0.1 ± 0.1 mm2. At 12 months target lesion revascularization rate was 3% and no stent thrombosis was reported. CONCLUSIONS: In this study the ihtDEStiny stent has shown a very low degree of neointimal proliferation associated with a low rate of uncovered/malapposed struts and total absence of subclinical thrombi at 9 months follow up.

Comparison of One-Year Outcomes Between the ihtDEStiny BD Stent and the Durable-Polymer Everolimus- and Zotarolimus-Eluting Stents: A Propensity-Score-Matched Analysis.

OBJECTIVES: We sought to evaluate clinical outcomes in patients treated with the drug-eluting stent ihtDEStiny BD. BACKGROUND: The ihtDEStiny BD stent is a metallic sirolimus eluting stent with a biodegradable polymer with both drug and polymer coating the abluminal surface of the stent and balloon. METHODS: In this study, the clinical outcomes of a multicenter prospective registry of patients treated with this stent (DEStiny group) were analyzed and compared with those of a control group of patients treated with durable polymer everolimus or zotarolimus eluting stents (CONTROL group) paired by propensity score matching. Primary outcome was the target vessel failure (TVF) at 12 months defined as a composite of cardiac death, target vessel myocardial infarction (TV-MI) and target vessel revascularization (TVR). RESULTS: A total of 350 patients were included in the DESTtiny group. The control group consisted initially of 1368 patients, but after matching (1:1) 350 patients were selected as CONTROL group. The baseline clinical, angiographic and procedural characteristics were quite comparable in both groups. At 12 months follow up the TVF was 6.6% in DEStiny group and 6.3% in CONTROL group (p = 0.8). No differences were observed for any of the individual components of the primary endpoint: cardiac death 1.1% vs. 1.4%, TV-MI 3.4% vs. 3.7% and TVR 2.6% vs. 2.3% respectively. CONCLUSIONS: The use of ihtDEStiny stent in real practice is associated with a clinical performance at 12 months follow up that appears to be non-inferior to the most widely used and largely evidence supported durable polymer drug eluting stents. A longer follow up is warranted.

Outcomes of predefined optimisation criteria for intravascular ultrasound guidance of left main stenting.

AIMS: This study sought to investigate the prognostic effect of a protocol with optimisation targets for intravascular ultrasound (IVUS)-guided left main (LM) revascularisation. METHODS AND RESULTS: A protocol was prospectively applied for IVUS-guided LM revascularisation (IVUS-PRO group) including predefined optimisation targets. Using propensity score matching, we selected as control groups patients with angiography-guided PCI (ANGIO group) and IVUS-guided PCI (IVUS group) from a large multicentre registry. The primary endpoint was a composite of cardiac death, LM-related infarction and LM revascularisation at 12 months. In each group, 124 patients with comparable characteristics were included. The incidence of the primary outcome was significantly higher in the ANGIO group compared to the IVUS-PRO group (12.9% vs 4.8%, HR 0.35, 95% CI: 0.15 to 0.82, p=0.02), but not with respect to the IVUS group (12.9% vs 8%, HR 0.51, 95% CI: 0.20 to 1.22, p=0.1), driven by a lower rate of LM revascularisation (8% in the ANGIO group, 6.4% in the IVUS group and 3.2% in the IVUS-PRO group). IVUS-PRO resulted in being an independent risk predictor (HR 0.45, 95% CI: 0.15 to 0.98; p=0.041). CONCLUSIONS: IVUS guidance of LM stenting provides prognostic benefit with respect to the use of angiography alone, particularly when following a protocol with these predefined optimisation criteria.

Procedural resources utilization and clinical outcomes with bioresorbable everolimus-eluting scaffolds and Pt-Cr everolimus-eluting stent with resorbable abluminal polymer in clinical practice. A randomized trial.

OBJECTIVES: We sought to compare the procedural implications of using bioresorbable everolimus-eluting scaffolds (BVS) and Pt-Cr everolimus-eluting stent with abluminal bioabsorbable polymer (Synergy). BACKGROUND: There are important differences in the respective platforms, which could impact on procedural performance, complications and outcomes. METHODS: A prospective, randomized single center study including consecutive patients in stable clinical condition and with lesions amenable to be treated with BVS according to predefined criteria. Patients were randomized to either treatment with BVS or Synergy. All procedural data were collected and 12 months clinical follow up conducted. Primary objectives were fluoroscopy time, median dose-area product, contras agent volumen, and peri-procedural troponin release. RESULTS: A total of 200 patients were included, 100 in BVS group and 100 in Synergy group. No significant differences were observed in baseline clinical and angiographic characteristics. Predilatation (97.6 vs. 25.4%; P < 0.001), postdilatation (64.8 vs. 38.4%: P < 0.01), and use of 2 wires (20.8 vs. 10%; P = 0.02) were more frequent with BVS. The BVS group showed a significant increase in fluoroscopy time (18%), dose-area product (20%), and contrast volume (10%). Post-procedural increase of creatinine was similar and amount of TnI release was significantly higher with BVS but incidence of peri-procedural infarction was comparable. Clinical outcomes at 12 months were similar with definite thrombosis being 1% with BVS and 0% with Synergy. CONCLUSIONS: The use of BVS in comparison with the Synergy stent in a similar lesional setting is associated with a higher use of resources in the procedure, more radiation, and higher TnI release. © 2016 Wiley Periodicals, Inc.

Clinical outcomes after intravascular ultrasound and fractional flow reserve assessment of intermediate coronary lesions. Propensity score matching of large cohorts from two institutions with a differential approach.

AIMS: Assessment of intermediate coronary lesions can be done with fractional flow reserve (FFR) and intravascular ultrasound (IVUS). There are no randomised trials and only a small registry from one centre is available but this is subject to important bias. We sought to evaluate the clinical outcomes of an FFR strategy compared with an IVUS strategy for intermediate lesion assessment. METHODS AND RESULTS: We compared the outcome of patients assessed with FFR and IVUS in two centres with a differential approach. After propensity score matching 400 pairs of patients were included. Revascularisation was done when FFR was <0.75 or minimum lumen area was <4 mm2 in vessels >3 mm, and <3.5 mm2 in vessels 2.5-3 mm, along with plaque burden >50%. After FFR and IVUS, 72% and 51.2% of lesions, respectively, were left untreated (p<0.001). At one and two years no significant differences in MACE-free survival were observed in overall groups (97.7% at one year and 93.1% at two years in the FFR group and 97.7% at one year and 95.6% at two years in the IVUS group; p=0.35) and among those with deferred intervention (97.9% at one year and 94.2% at two years in the FFR group and 96.5% at one year and 93.6% at two years in the IVUS group; p=0.7). CONCLUSIONS: IVUS and FFR may be safely used to defer revascularisation of intermediate lesions. IVUS induces a higher degree of revascularisation but much lower than previously reported and does not affect the clinical outcome.

A real all-comers randomized trial comparing Xience Prime and Promus Element stents.

BACKGROUND: The cobalt chromium everolimus-eluting stent (CoCr-EES) has shown the best safety and efficacy profile in the trials conducted so far. Recently, a new EES with a platinum-based platform (PtCr-EES) has been introduced in the market. There is only one study comparing both stents, but with important exclusion criteria. OBJECTIVES: We sought to evaluate clinical outcomes with the PtCr-EES compared with the CoCr-EES in an all-comers population. We have conducted a randomized all-comers study aimed to compare these stents in a real-practice scenario. METHODS: A total of 300 patients undergoing revascularization and suitable for long-term dual-antiplatelet therapy were randomized 1:1 to CoCr-EES or PtCr-EES. No exclusion criteria based on clinical presentation or lesion characteristics were applied. RESULTS: The clinical and angiographic characteristics were well balanced in both groups without significant differences. At 18 months, the survival free from death and infarction was 93.9% for CoCr-EES and 91.3% for PtCr-EES (P=.3), the survival free from revascularization was 95.2% vs 94.5% (P=.6) and the survival free from death, infarction, and revascularization was 90.6% vs 88%, respectively (P=.4). The incidence of definite or probable thrombosis was 1.3% for CoCr-EES and 0.66% for PtCr-EES (P=.9). No cases of longitudinal stent compression were observed. CONCLUSIONS: The results of this all-comers trial do not show significant differences between CoCr-EES and PtCr-EES. However, the sample size is not powered to exclude potential differences between stents.

Comparison of paclitaxel-eluting vs. everolimus-eluting stents implanted simultaneously in different lesions of the same coronary artery: 12-month follow-up with optical coherence tomography.

AIMS: Optical coherence tomography (OCT) allows a detailed assessment of intimal coverage and strut apposition which are well known substrates for late thrombosis. This study sought to assess and compare long-term coverage and apposition of PES and EES implanted in different lesions of the same coronary artery (and in the same patient). METHODS AND RESULTS: A total of 30 patients were included. In these patients PES and EES were implanted in the same vessel in two similar lesions. The selection of the stent for each lesion was random. At 12 months, 30 PES were examined analysing 154±90 struts/stents and 30 EES analysing 158±72 struts/stents. The proportion of uncovered struts was 0.8±1.3% for EES and 1.5±2.9% for PES (p=0.3), and the proportion of malapposed struts was 1.25±2.1% and 0.98±2%, respectively (p=0.2). A pooled analysis was performed using the random effects model, given the significant heterogeneity found, which did not show significant differences between EES and PES for non-coverage (RR 0.73, 95% CI: 0.32-1.67) or malapposition (RR 1.60, 95% CI: 0.56-4.61). The presence of non-coverage in malapposed struts was 62% with PES and 15% with EES (p<0.0001), the maximal malapposition area being significantly larger with PES (0.6±0.3 vs. 0.25±0.2 mm², p=0.001). CONCLUSIONS: In highly matched conditions, with PES and EES implanted in the same artery, both DES showed a comparable degree of intimal coverage and apposition at one-year follow-up. A smaller area of malapposition with non-covered struts was found with EES.

Impact of drug eluting stents on the clinical practice of revascularisation of coronary artery disease.

AIMS: Drug-eluting stents (DES) have shown to reduce restenosis rates in all lesional subsets. This has expanded the application of percutaneous intervention (PCI). In this study we address the impact of the high DES penetration on the management of patients referred for coronary angiography. METHODS AND RESULTS: We have studied the cohorts of patients referred for coronary angiography in 2000-2001 prior to DES availability, and in 2005-2006 with a 73% DES implementation. In 2000-1 of 2,458 coronary angiographic studies, 84% had significant lesions (>50%), 56% had PCI, 8.8% had CABG and in 443 (18%) with significant lesions no revascularisation was attempted. In 2005-6 out of 2,600 angiographies, 84% had significant lesions, 64% had PCI, 6% had CABG and in 312 (12%) with significant lesions no revascularisation was done. The increase in PCI, the reduction in CABG and the decrease in non-revascularised diseased cases were all significant (p<0,001). The PCI and CABG groups in 2005-6 compared to 2000-1 had a more complex lesion profile with, however, less in-stent restenotic lesions treated (10% vs 4.2%; p<0.001). CONCLUSIONS: The wide clinical introduction of DES was associated with a significant increase in patients undergoing any kind of revascularisation, increasing the PCI volume to the detriment of CABG activity. Patients with PCI in 2006 had more complex lesions treated, whereas restenosis was less frequent.

Virtual histology intravascular ultrasound assessment of cardiac allograft vasculopathy from 1 to 20 years after heart transplantation.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is the main cause of graft loss and death in heart transplant (HTx) recipients surviving >1 year. There is a dual etiology for coronary disease in HTx: classic atherosclerosis and an immunologically mediated disease. Intravascular ultrasound (IVUS) is highly sensitive for CAV detection; however, gray-scale IVUS is of limited value for identification of specific plaque components. We sought to characterize graft coronary artery disease by means of IVUS-virtual histology (IVUS-VH) at different time-points of follow-up and to correlate plaque composition with clinical factors. METHODS: In our study we included 67 patients, who were 7.6 +/- 5.7 years post-HTx. IVUS gray-scale evaluation was performed on all patients. IVUS-VH analysis was done in those patients showing intimal thickening >0.5 mm at the three more significant lesions (three cross-sections for each) of the left anterior descending artery. RESULTS: IVUS-VH analysis was obtained done on 58 patients (86.5%). We found a significant correlation between time of HTx and IVUS gray-scale parameters (plaque area and plaque burden), with both increasing over time. We also found a significant correlation between time and IVUS-VH-derived plaque components, necrotic core and calcium, which increased with time, and fibrous and fibrofatty components, both decreased at follow-up. IVUS-VH results were also related to donor age and cardiovascular risk factors. CONCLUSIONS: We observed a time-related change in IVUS-VH-derived plaque composition. Necrotic core and calcium, typical atheromatous components, become more prevalent with time after HTx, especially when influenced by cardiovascular risk factors. The presence of a necrotic core in the early stages was linked to older donor age.

[Prospective use of an intravascular ultrasound-derived minimum lumen area cut-off value in the assessment of intermediate left main coronary artery lesions]. / Aplicación prospectiva de un valor de corte de área luminal mínima por ecografía intravascular en la evaluación de lesiones intermedias del tronco.

BACKGROUND AND OBJECTIVES: Angiographic assessment of the severity of intermediate lesions in the left main coronary artery (LMCA) is subject to significant limitations. Intravascular ultrasound (IVUS) can provide accurate measurement, but there is no agreement on the minimum lumen cross-sectional area (MLA) that indicates significant disease. The aim of this study was to determine the long-term safety of applying a cut-off value of 6 mm2 for the MLA in the LMCA. METHODS: The study included patients with intermediate lesions (i.e., 25-50%) in unprotected LMCAs, with no previous evidence of associated ischemia. An IVUS examination was carried out and revascularization was indicated when the MLA was < or =6 mm2. RESULTS: In total, 79 patients were recruited between 2000-2005. In 31 (39%), the MLA was < or =6 mm2, and they underwent LMCA revascularization; in the remaining 48 (61%), the MLA was >6 mm2, and patients either underwent angioplasty for other lesions (n=37) or continued medical treatment (n=11). In a follow-up period of 40 [17] months, four patients (8.3%) died from heart disease, all of whom had an MLA between 9-10 mm2 in the baseline study. Revascularization of the LMCA was necessary in only two patients (4.2%), both of whom had elective surgery more than 2 years after the initial study. CONCLUSIONS: Intravascular ultrasound assessment of intermediate LMCA lesions using an MLA cut-off value of 6 mm2 appears safe over the long term provided the clinical and angiographic criteria applied to patient selection are similar to those used in this study.

Aplicación prospectiva de un valor de corte de área luminal mínima por ecografía intravascular en la evaluación de lesiones intermedias del tronco / Prospective use of an intravascular ultrasound-derived minimum lumen area cut-off value in the assessment of intermediate left main coronary artery lesions

Introducción y objetivos. La angiografía presenta limitaciones importantes para definir la severidad de las lesiones intermedias del tronco común. La ecografía endovascular (EEV) permite realizar una evaluación precisa, pero no hay consenso respecto a los valores de área luminal mínima (ALM) que indican significación. El objetivo de este estudio es evaluar la seguridad a largo plazo de la aplicación de un valor de corte de 6 mm2 para el ALM en el tronco. Métodos. Se ha incluido a pacientes con lesiones intermedias (25-50%) de tronco no protegido, sin datos previos indicativos de isquemia atribuible. Se realizó estudio con EEV y se indicó revascularización en los pacientes con ALM ≤ 6 mm2. Resultados. En el período 2000-2005 se ha incluido a 79 pacientes, en 31 (39%) el ALM fue ≤ 6 mm2 y recibieron revascularización del tronco, en los restantes 48 (61%) el ALM fue > 6 mm2 y sólo se actuó sobre otras lesiones (n = 37) o continuaron con tratamiento médico (n = 11). En un seguimiento de 40 ± 17 meses se han producido 4 muertes cardiacas (8,3%), que ocurrieron en casos con un ALM de 9-10 mm2 en el estudio basal. Sólo en 2 casos (4,2%) fue preciso efectuar procedimientos de revascularización del tronco que consistieron en cirugías electivas tras más de 2 años del estudio inicial. Conclusiones. La evaluación con EEV de las lesiones intermedias de tronco y la consideración de un valor de corte de 6 mm2 para el ALM resulta segura a largo plazo, siempre que se consideren unos criterios clinicoangiográficos de aplicabilidad como los considerados en este estudio (AU)

Background and objectives. Angiographic assessment of the severity of intermediate lesions in the left main coronary artery (LMCA) is subject to significant limitations. Intravascular ultrasound (IVUS) can provide accurate measurement, but there is no agreement on the minimum lumen cross-sectional area (MLA) that indicates significant disease. The aim of this study was to determine the long-term safety of applying a cut-off value of 6 mm2 for the MLA in the LMCA. Methods. The study included patients with intermediate lesions (i.e., 25­50%) in unprotected LMCAs, with no previous evidence of associated ischemia. An IVUS examination was carried out and revascularization was indicated when the MLA was ≤6 mm2. Results. In total, 79 patients were recruited between 2000­2005. In 31 (39%), the MLA was ≤6 mm2, and they underwent LMCA revascularization; in the remaining 48 (61%), the MLA was >6 mm2, and patients either underwent angioplasty for other lesions (n=37) or continued medical treatment (n=11). In a follow-up period of 40 [17] months, four patients (8.3%) died from heart disease, all of whom had an MLA between 9­10 mm2 in the baseline study. Revascularization of the LMCA was necessary in only two patients (4.2%), both of whom had elective surgery more than 2 years after the initial study. Conclusions. Intravascular ultrasound assessment of intermediate LMCA lesions using an MLA cut-off value of 6 mm2 appears safe over the long term provided the clinical and angiographic criteria applied to patient selection are similar to those used in this study (AU)

[Two-year clinical follow-up in 200 patients receiving sirolimus-eluting stents in lesions at a high risk of restenosis]. / Seguimiento clínico a 2 años de 200 pacientes tratados con stent liberador de rapamicina en lesiones de alto riesgo de reestenosis.

INTRODUCTION AND OBJECTIVES: Sirolimus-eluting stents (SESs) have been shown to reduce the rate of restenosis significantly in all types of coronary lesion. However, reports of late cases of thrombosis and restenosis have raised questions about long-term outcome in patients treated with these stents. Our aim was to evaluate long-term outcome in patients undergoing SES placement in lesions at a high risk of restenosis. PATIENTS AND METHOD: Since SESs became available, we have used them to treat lesions at risk of restenosis. We studied clinical outcomes in consecutive patients treated with SESs who were followed up for more than 2 years. RESULTS: The study included 200 patients (age 60[11] years, 22% diabetics) who were treated between June 2002 and April 2003 for 309 lesions: 16% were total occlusions, 16.8% in-stent restenoses, 28% diffuse lesions, and 30% small-vessel lesions. The total stent length per patient was 29 (16) mm and the mean diameter was 2.78 (0.27) mm. In a mean clinical follow-up period of 29 (3.2) months (range 24-34 months), there were four deaths, two (1%) of which were cardiac, four (2%) non-fatal infarctions, four (2%) in-stent thromboses (all occurred late, at 3, 7, 26 and 31 months), four (2%) cases requiring target lesion revascularization (at 3, 5, 14 and 15 months), and six (3%) requiring revascularization of a new lesion. CONCLUSIONS: Long-term follow-up of patients undergoing SES placement in lesions at a high risk of restenosis revealed a very low restenosis rate. However, the incidence of late thrombosis appeared to be elevated and warrants further evaluation in larger studies.