Optimizing vessel healing following drug eluting stent implantation with biodegradable polymer DES.

The introduction of coronary drug eluting stents (DES) more than 10 years ago drastically decreased the occurrence of restenosis, compared with first generation bare metal stents (BMS). However, the optimism created by the first studies was soon shadowed by the demonstration of higher rates of late and very late stent thrombosis (ST). The research performed in this phenomenon highlighted the causative role played by incomplete stent strut coverage, hypersensitivity reactions caused by the drug eluting polymer, and neoatherosclerosis, all markers of an inadequate vascular response to DES implantation. Over the following years, new development in stent and eluting polymer technologies have been incorporated in second generation DES to optimize the process of vessel healing and, thus, to avoid these complications. Furthermore, it is envisaged that adequate vessel healing would be followed by less dependence on double antiplatelet, a limiting aspect for DES use in different clinical scenarios. In this review, we focused on the use of biodegradable eluting polymers to increase DES safety, revisiting the rationale for its use and the synergic action with other changes in stent technology aimed to optimize vessel healing after DES implantation.

Técnicas de imagen no invasivas para el estudio de los aneurismas coronarios / Noninvasive imaging techniques to study coronary artery aneurysms

Ante la evidencia del uso cada vez mayor de las endoprótesis con membrana para tratar los aneurismas coronarios, resulta fundamental conocer con precisión la anatomía del aneurisma para seleccionar correctamente a los pacientes. La coronariografía invasiva presenta limitaciones diagnósticas y puede subestimar el verdadero tamaño del aneurisma. En el presente artículo se realiza una revisión acerca de las técnicas de imagen no invasivas disponibles en la actualidad para estudiar los aneurismas coronarios, y se muestran ejemplos de la utilidad de cada una de ellas (AU)

Given the growing evidence about the use of membrane-covered stents to treat coronary artery aneurysms, it is fundamental to know the exact anatomy of the aneurysm to enable patients to be selected correctly. Invasive heart catheterization has limitations for diagnostic purposes and can underestimate the size of the aneurysm. In this article, we review the noninvasive diagnostic imaging techniques for the study of coronary artery aneurysms, illustrating the usefulness of each technique (AU)

[Noninvasive imaging techniques to study coronary artery aneurysms]. / Técnicas de imagen no invasivas para el estudio de los aneurismas coronarios.

Given the growing evidence about the use of membrane-covered stents to treat coronary artery aneurysms, it is fundamental to know the exact anatomy of the aneurysm to enable patients to be selected correctly. Invasive heart catheterization has limitations for diagnostic purposes and can underestimate the size of the aneurysm. In this article, we review the noninvasive diagnostic imaging techniques for the study of coronary artery aneurysms, illustrating the usefulness of each technique.

Relevancia clínica del tratamiento farmacológico completo precoz en el pronóstico del síndrome coronario agudo sin elevación del ST / Clinical importance of early intensive medical treatment for improving prognosis in non-ST-elevation acute coronary syndrome

Objetivo: Las guías actuales insisten en la relevancia de un tratamiento farmacológico optimizado para mejorar el pronóstico de los pacientes diagnosticados de síndrome coronario agudo sin elevación del segmento ST (SCASEST), pero son pocos los estudios que analizan sus resultados. El presente estudio analiza este aspecto. Método: Se incluyeron en una cohorte retrospectiva 1.118 pacientes ingresados en la unidad coronaria con el diagnóstico de SCASEST, y se analizaron sus (..) (AU)

Background and objective: Current guidelines emphasize the importance of optimal medical treatment for improving the prognosis of patients diagnosed with acute coronary syndrome without persistent ST-segment elevation, although few studies have analyzed the importance of implementing prescribing guidelines on (..) (AU)

Heart failure and non-ST-segment elevation myocardial infarction: a review for a widespread situation.

Up to 15% of patients with NSTEMI present at admission with heart failure. Scientific evidence for its management is limited but much progress has been made during the last years. Our purpose was to review the last data concerning heart failure in NSTEMI and perform an update on the subject, with the following findings as main highlights. As Killip classes III and IV, Killip class II onset in the context of NSTEMI has also proven bad prognosis significance. Beta-blocker therapy has proven benefit to patients with Killip class II in observational studies and small trials. Angiotensin-converting enzyme inhibitor therapy shows stronger evidence of benefit in patients with heart failure than in patients without it. Eplerenone is indicated for patients with left ventricular dysfunction and heart failure or diabetes mellitus. Implantable cardioverter defibrillators improve survival in patients with severe ventricular dysfunction after a myocardial infarction. Cardiac resynchronization therapy indications must be carefully assessed due to the high rate of implants that do not fulfill guidelines indications. In conclusion, heart failure during a NSTEMI is a common and meaningful situation which warrants careful management and further investigation to reach stronger evidence for clinical recommendations.

Increased cyclic guanosine monophosphate production and endothelial nitric oxide synthase level in mononuclear cells from sildenafil citrate-treated patients with erectile dysfunction.

Mononuclear cells express enzymes involved in the NO/cyclic guanosine monophosphate (cGMP) generating system, as well as PDE5. The objective of the study was to determine the effect of sildenafil citrate administration on the level of proteins involved in the NO/cGMP generating system in mononuclear cells from patients with ED. Twenty-one patients with ED (International Index of Erectile Function-Erectile Function Domain (IIEF-EFD) 17.9+/-0.8) were enrolled and 100 mg sildenafil citrate on-demand was administered during 12 weeks. All patients showed cardiovascular risk factors. After sildenafil citrate administration, IIEF-EFD score was improved (26+/-1.2 P<0.05). In the mononuclear cells, the protein level of endothelial NO synthase (eNOS) was higher after sildenafil citrate treatment. It was accompanied by reduction in the circulating plasma levels of both high-sensitive C-reactive protein and soluble intercellular adhesive molecule-1. The protein level of soluble guanylate cyclase and PDE5 did not change in the mononuclear cells after sildenafil citrate treatment. However, in the mononuclear cells exogenous NO induced a higher cGMP production after 12-weeks sildenafil citrate administration. In conclusion, in mononuclear cells from patients with ED sildenafil citrate administration increased the level of eNOS protein and increased cGMP production in response to NO. Moreover, sildenafil citrate administration reduced the plasma circulating levels of two biomarkers associated with inflammation.

Sirolimus-eluting stents, bare metal stents or coronary artery bypass grafting for patients with multivessel disease including involvement of the proximal left anterior descending artery: analysis of the Arterial Revascularization Therapies study part 2 (ARTS-II).

OBJECTIVE: The The Arterial Revascularization Therapies Study (ARTS)-II trial found no differences in survival or overall adverse events between sirolimus-eluting stents (SES) and the surgical arm of ARTS-I. Nevertheless, existing data suggest that patients with disease of the proximal left anterior descending artery (LAD) may derive particular benefit from coronary artery bypass grafting (CABG). We therefore analysed the clinical outcome of patients in ARTS-I and ARTS-II with proximal LAD involvement. DESIGN: Multicentre observational study. SETTING: Forty-five European academic hospitals. PATIENTS: Patients with multivessel coronary artery disease. INTERVENTIONS: Patients in ARTS-II with proximal LAD disease treated with SES (289/607, 48%) were compared with 187/600 (31%) bare metal stent patients (ARTS-I BMS) and 206/605 (34%) surgical patients (ARTS-I CABG) with proximal LAD involvement from ARTS-I. MAIN OUTCOME MEASURES: Major adverse cardiac and cerebrovascular events after 3 years. RESULTS: The Arterial Revascularization Therapies study part 2 (ARTS-II) subgroup had better survival than both ARTS-I groups (ARTS-II 98.6% vs ARTS-I BMS 95.7%, p = 0.05 and vs ARTS-I CABG 94.7%, p = 0.01) and lower rates of the hard clinical composite endpoint of death or non-fatal myocardial infarction (ARTS-II 3.1% vs ARTS-I BMS 9.6%, p = 0.002 and vs ARTS-I CABG 9.7%, p = 0.002). Although the ARTS-I CABG patients had a lower need for repeat revascularisation than ARTS-II (5.3% vs 13.1%, p = 0.002), the overall composite adverse event rates (death, myocardial infarction, stroke or any repeat revascularisation) were not significantly different between the ARTS-I CABG and ARTS-II patients (15.0% vs 18.0%, p = 0.4). CONCLUSIONS: SES are not inferior to CABG or bare metal stents for the treatment of patients with multivessel coronary disease including involvement of the proximal LAD.

Cooled ablation reduces pulmonary vein isolation time: results of a prospective randomised trial.

BACKGROUND: Currently, selection of the ablation catheter for pulmonary vein (PV) isolation is a matter of choice. OBJECTIVE: To evaluate the efficiency of cooled ablation for PV isolation. METHODS: A prospective randomised trial was carried out comparing the time required to disconnect each targeted PV using cooled ablation (open irrigation at 15 ml/min, group A) or standard temperature-controlled 4 mm tip catheter ablation (group B). The ablation parameter limit settings were 45 degrees C, 35 (5) W in group A, and 55 degrees C, 35 (5) W in group B. RESULTS: Thirty-six patients referred for a first atrial fibrillation (AF) ablation procedure were randomised to group A or group B (18 patients in each group). There were no significant differences in baseline characteristics between the groups. Bidirectional block was achieved in 61/61 PVs from group A (100%) and 59/61 PVs from group B (97%); p = NS. Time to PV disconnection was significantly shorter in group A than in group B (median (25th-75th centiles) 14 (5-28) min vs 19 (14-32) min, respectively; p = 0.003). Five asymptomatic PV stenoses were identified by MRI, all in group B (p = 0.05). After 1-year minimum follow-up, AF recurrences were less frequently documented in patients treated with cooled ablation (6% vs 33%; p = 0.05). CONCLUSION: Cooled ablation is more efficient than standard ablation in achieving PV isolation. Results obtained from this study also suggest a potential benefit of clinical efficacy and safety from cooled ablation, which should be further evaluated in larger clinical trials.

Aspectos proteómicos y genéticos de la resistencia a la aspirina / Proteomics and genetics aspects of aspirin resistance

Objetivo: Analizar si existe alguna asociación entre la resistencia a aspirina (RA) y la presencia de polimorfismos genéticos de un único nucleótido (SNPs) en el gen de la COX-1, así como su relación con modificaciones en la expresión de proteínas plasmáticas en pacientes con enfermedad isquémica estable y tratamiento continuado de aspirina. Materiales y métodos: Analizamos el proteoma plasmático de 19 pacientes sensibles, 19 resistentes. RA se definió mediante el sistema PFA-100. Se realizó electroforesis bidimensional (IPG 17cm, pH(4-7), geles SDS-PAGE 10%) y tinción con plata. Se analizaron cambios en tres SNPs (A-842G, C22T y C50T) en 50 pacientes sensibles, 33 resistentes y 83 controles mediante PCR a tiempo real. Resultados: La expresión de cuatro isoformas de alfa1-antitripsina estaba aumentada en los pacientes resistentes. No encontramos diferencias en la expresión de ceruloplasmina, precursor de haptoglobina, apolipoproteína AI y precursor de albúmina entre ambos tipos de pacientes. Ningún paciente presentó cambios en el SNP A-842G. La frecuencia de cambio en C22T y C50T fue relativamente baja con respecto a la población total. Conclusiones: No encontramos asociación entre la presencia de polimorfismos en el gen de la COX-1 y la peor respuesta a la aspirina. Los cambios en observados alfa1-antitripsina podrían estar relacionados con un diferente estado inflamatorio entre ambos tipos de pacientes (AU)

Aim: To evaluate the existence of a possible association between Aspirin resistance (AR), COX-1 single-nucleotide polymorphisms (SNPs) and the modifications in the plasma proteome of clinically stable coronary patients. Materials and methods: AR was defined according to the PFA-100 assay. AR-sensitive and AR-resistant patients had been taken aspirin for the last 9 months. The proteomic study (19 AR-sensitive, 19 AR-resistant) was performed using IPG strips (17cm, pH 4-7), SDS-PAGE gels (10%) and silver staining. We study three SNPs (A- 842G, C22T y C50T) in 50 AR-sensitive patients, 33 AR-resistant and 83 controls using a real-time PCR. Results: The expression of four alpha1-antitripsin isoforms was increased in the aspirin-resistant patients. No differences were found in the expression of ceruloplasmin, haptoglobin-precursor, apolipoprotein-AI and albumin- precursor between both groups of patients. The A-842G SNP was undetectable in all subjects. The remaining two SNPs (C22T y C50T) showed a low frequency with respect the global population. Conclusions: The low SNPs frequencies were unlikely to explain the difference in aspirin responsiveness between both groups of patients. The changes in alpha1-antitripsin could be linked with a different inflammatory state in these patients (AU)

Hospitalizaciones por insuficiencia cardiaca descompensada en España / Hospitalizations due to decompensated cardiac insufficiency in Spain

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Clinical variables related with in-stent restenosis late regression after bare metal coronary stenting

In-stent restenosis (ISR) has an incidence between 20% and 30% using bare metal stents. ISR late regression phenomenon (ISRLR) has been previously described, but clinical variables related with this phenomenon remain unclear. The aim of the study was to identify the variables related with ISRLR. METHODS: We identified from our data base 30 patients between November 1995 and September 2002 that fulfilled the following criteria: 1) Documented ISR at follow-up angiography (CA-1); 2) treated medically; and 3) Referred for a second follow-up angiography (CA-2). at least 3 months after CA-1. ISRLR was defined as a > 0.2 mm increase in MLD between CA-1 and CA-2, calculated as the 2-fold of our inter-observer variability. ISR late progression was defined as a > 0.2 mm decrease in minimum lumen diameter (MLD) between CA-1 and CA-2. RESULTS: At the time of CA-2 only 2 patients (6.7%) had symptoms related with the previously stented vessel. We found a mean MLD of 1.03+/-0.34 mm and 1.54+/-0.48 mm at CA-1 and CA-2 respectively (AMLD = 0.51 +/-0.34 mm; p < 0.001). Twenty four patients (80.0%) had ISRLR. Two variables were related to the presence or absence ISRLR: Current smoking at the time of coronary stenting (70.8% vs 20.0% respectively, p = 0.026) and acute coronary syndrome as clinical indication for coronary stenting (and 83.5% vs 40.0% respectively, p = 0.029). CONCLUSION: ISRLR is a frequent phenomenon in patients with ISR treated medically, probably contributing to the benign long-term clinical outcome that has been previously described in patients with asymptomatic or mildly symptomatic ISR. Current smoking at the time of coronary stenting and acute coronary syndrome as clinical indication for coronary stenting are associated with this phenomenon.

WITHDRAWN: Effect of Intensive Diuretic Treatment over Right Ventricular Behaviour. Evidence Provided from Colour and Pulsed-wave Doppler Echocardiography.

The publisher regrets that this was an accidental duplication of an article that has already been published in Eur. J. Echocardiogr., 4 (2003) 226-228, . The duplicate article has therefore been withdrawn.

Occupational radiation doses in interventional cardiology: a 15-year follow-up.

This report describes occupational radiation doses of interventional cardiologists over 15 years and assesses action undertaken to optimize radiation protection. Personal dosimetry records of nine staff cardiologists and eight interventional cardiology fellows were recorded using personal dosemeters worn over and under their lead aprons. The hospital in which this study was conducted currently performs 5000 cardiology procedures per year. The hospital has improved its facilities since 1989, when it had two old-fashioned theatres, to include four rooms with more advanced and safer equipment. Intensive radiation protection training was also implemented since 1989. Initially, some individual dose values in the range of 100-300 mSv month(-1), which risked exceeding some regulatory dose limits, were measured over the lead apron. Several doses in the range of 5-11 mSv month(-1) were recorded under the apron (mean = 10.2 mSv year(-1)). During the last 5 years of the study, after the implementation of the radiation protection actions and a programme of patient-dose optimization, the mean dose under the apron was reduced to 1.2 mSv year(-1). Current mean occupational doses recorded under the lead apron are 14% of those recorded during 1989-1992 and those recorded over the apron are 14-fold less than those recorded during 1989-1992. The regulatory dose limits and the threshold for lens injuries might have been exceeded if radiation protection facilities had not been used systematically. The most effective actions involved in reducing the radiation risk were training in radiation protection, a programme of patient-dose reduction and the systematic use of radiation protection facilities, specifically ceiling-suspended protective screens.

Soluble guanylate cyclase beta1-subunit expression is increased in mononuclear cells from patients with erectile dysfunction.

The aim was to determine in circulating mononuclear cells from patients with erectile dysfunction (ED), the level of expression of endothelial nitric oxide synthase (eNOS), soluble guanylate cyclase (sGC) beta1-subunit and phosphodiesterase type-V (PDE-V). Peripheral mononuclear cells from nine patients with ED of vascular origin and nine patients with ED of neurological origin were obtained. Fourteen age-matched volunteers with normal erectile function were used as control. Reduction in eNOS protein was observed in the mononuclear cells from patients with ED of vascular origin but not in those from neurological origin. Although sGC beta1-subunit expression was increased in mononuclear cells from patients with ED, the sGC activity was reduced. However, only the patients with ED of vascular origin showed an increased expression of PDE-V. This work shows for the first time that, independently of the aetiology of ED, the expression of sGC beta1-subunit was increased in circulating mononuclear cells; however, the expression of both eNOS and PDE-V was only modified in the circulating mononuclear cells from patients with ED of vascular origin.

Involvement of endothelium and endothelin-1 in lead-induced smooth muscle cell dysfunction in rats.

Lead exposure induces dysfunction of the cyclic guanosine monophosphate-dependent vasodilator system through downregulation of soluble guanylate cyclase (sGC) expression. The endothelium not only releases vasodilators but also vasoconstrictors such as endothelin-1 (ET-1). Our aim was to explore the role of the vascular endothelium and ET-1 as possible mediators of lead-induced downregulation of sGC. Isolated aortic segments from Wistar Kyoto rats were incubated in the presence or absence of lead (1 parts per million) for 24 h. Endothelium was mechanically removed in some of the aorta segments. As reported previously, lead exposure induced downregulation of sGC protein expression in the intact aortic segments. However, lead exposure failed to significantly modify sGC-beta1 subunit expression in the endothelium-denuded aortic segments. Incubation with a selective ETA-type receptor inhibitor, BQ-123 (10(-6) mol/l), restored sGC protein expression in lead-exposed intact aortic segments. As it has also been previously observed, incubation in lead-containing medium resulted in the upregulation of cyclooxygenase-2 (COX-2) in the intact aortic segments. Denudation of endothelium partially abrogated this effect of lead. Incubation with BQ-123 prevented the lead-induced upregulation COX-2 in the intact aortic segments. However, neither ET-1 content nor ETA-type receptor expression were modified by lead exposure of the aortic segments. As conclusion, the endothelium through the activation of ETA-type receptors mediates the downregulation of sGC expression by lead in the vascular wall.

Findings of intravascular ultrasound during acute stent thrombosis.

OBJECTIVE: To evaluate the potential role of intravascular ultrasound (IVUS) in evaluating patients experiencing an episode of acute stent thrombosis. DESIGN AND SETTING: Prospective observational study in a cardiac catheterisation laboratory in a university teaching hospital. PATIENTS AND INTERVENTIONS: IVUS was used to examine 12 patients undergoing coronary interventions for stent thrombosis to gain further mechanistic insights and to guide treatment. IVUS studies were obtained before and after intervention with a motorised pullback device. MAIN OUTCOME MEASURES: Qualitative and volumetric IVUS analyses. RESULTS: Angiographically, 10 patients had occluded vessels and two patients had intraluminal filling defects within the stent. IVUS showed an occlusive thrombus in all patients. Thrombus volume was 90 (77) mm3, which was 51 (21)% of total stent volume. There was evidence of severe stent underexpansion in most patients and no patient fulfilled standard criteria for optimal stent implantation. Stent malapposition was detected in four patients, edge dissections were seen in two patients, and significant inflow-outflow disease was present in 11 patients. During interventions IVUS findings led to the use of higher pressures or larger balloons than those used during initial stenting in 10 patients. In addition, four patients required additional stenting, whereas a thrombectomy device alone was selected for one patient. After the procedure final minimum stent area (7.1 (2.1) v 5.3 (2) mm2, p < 0.005) and stent expansion (83.2 (17) v 62.1 (15)%, p < 0.005) improved compared with pre-interventional values. However, residual lining thrombus was still visualised in eight patients (25 (19) mm3, accounting for a 17% of final stent volume). CONCLUSIONS: IVUS provides an attractive technique to characterise fully the pattern of stent thrombosis, to identify readily the underlying mechanical predisposing factors, and to guide repeated coronary interventions.

Isovolumic contraction time by pulsed-wave Doppler tissue imaging in aortic stenosis.

BACKGROUND: Doppler Tissue Imaging (DTI) has been evaluated in ischaemic heart disease and some cardiomyopathies. In patients with aortic stenosis (AS), left ventricular contraction is slowered. This study aimed to evaluate the possible role of the measurement of isovolumic contraction time (ICT) by DTI in the evaluation of AS severity. METHODS: The study population constitutes 30 patients: 15 with AS (nine severe and six non-severe) and 15 control subjects. All of them had normal systolic function, sinus rhythm, and absence of ischaemic heart disease of conduction abnormalities. ICT was defined as the time from the onset of the QRS complex to the beginning of the DTI systolic wave. The correlation between ICT and aortic area obtained by continuity equation, as well as the diagnostic value of ICT in the identification of severe AS were studied. RESULTS: ICT was significantly increased in patients with severe AS (98+/-27 versus 65+/-21 ms, p=0.024). There was a significant correlation between ICT and aortic area (r=-0.56; p=0.035). The receiver operator characteristic curve of ICT in the identification of severe AS yielded an area under the curve of 0.852 (95% confidence interval: 0.665-1.0). The two best cut-points were >73 ms (88% sensitivity, 77% specificity) and >85 ms (78% sensitivity, 83% specificity). A value of >41 ms had a 100% sensitivity, but only a 17% specificity, and >91 ms showed a 100% specificity, but only a 44% sensitivity. CONCLUSIONS: ICT measured by pulsed-wave DTI is increased in patients with aortic stenosis.

Long term outcome of patients with postinfarction left ventricular pseudoaneurysm.

BACKGROUND: It is debatable whether surgical repair is routinely indicated in asymptomatic patients with left ventricular pseudoaneurysms. OBJECTIVE: To evaluate the long term outcome of patients with pseudoaneurysm after myocardial infarction, focusing on those treated conservatively. METHODS: 10 patients with postinfarction left ventricular pseudoaneurysm were followed up over a mean (SD) period of 3.8 (5.2) years. RESULTS: In those treated conservatively (n = 9), cumulative survival was 88.9 (10.5)% and 74.1 (16.1)% at one and four years, respectively. The probability of being free of cardiac death was 88.9 (10.5)% at both one and four years. No patient had complete fatal heart rupture during follow up. Three patients suffered ischaemic stroke (at 1, 11, and 62 months). The cumulative incidence of ischaemic stroke was 10% at one year and 32.5% at four years. CONCLUSIONS: Long term outcome of patients with postinfarction left ventricular pseudoaneurysm is relatively benign, with a very low risk (none in this series) of fatal rupture. Taking into consideration the relatively high risk of stroke, chronic anticoagulant treatment could be considered.

Effects of bosentan on neointimal response following coronary angioplasty.

BACKGROUND: Endothelins are important vasoconstrictors and cellular-growth promoters. ETA-specific antagonists have been shown to reduce neointimal response to injury in some experimental angioplasty models. However, there is little information on the effects of dual ETA/ETB receptor blockers, such as bosentan, on neointimal proliferation following experimental coronary angioplasty. MATERIALS AND METHODS: Coronary injury was achieved by directional atherectomy in the left anterior descending artery of 20 pigs. Animals were randomly assigned to receive a daily dose of oral bosentan (30 mg kg-1) (group I, n = 10) or no treatment (group II, n = 10). At 4 weeks, arteries were processed for histomorphometry and endothelin characterization. RESULTS: Vessel injury score was similar among the two groups. Overall, a linear correlation was found between injury and neointimal development (r = 0.57, P = 0.01). This correlation had a lower slope in group I compared with group II (P < 0.001), indicating a smaller amount of neointimal development for a similar degree of injury in bosentan-treated animals. Multivariate regression showed that neointimal response was reduced by oral treatment with bosentan (beta: -0.59 mm2, 95% CI: -1.11/-0.06 mm2). In addition, immunostaining revealed fewer positive endothelin areas in group I arteries. CONCLUSIONS: Oral treatment with bosentan reduces neointimal development following coronary angioplasty in this experimental model.