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1.
Pneumologie ; 77(11): 926-936, 2023 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-37963482

RESUMEN

Pulmonary hypertension associated with left heart disease (PH-LHD) corresponds to group two of pulmonary hypertension according to clinical classification. Haemodynamically, this group includes isolated post-capillary pulmonary hypertension (IpcPH) and combined post- and pre-capillary pulmonary hypertension (CpcPH). PH-LHD is defined by an mPAP > 20 mmHg and a PAWP > 15 mmHg, pulmonary vascular resistance (PVR) with a cut-off value of 2 Wood Units (WU) is used to differentiate between IpcPH and CpcPH. A PVR greater than 5 WU indicates a dominant precapillary component. PH-LHD is the most common form of pulmonary hypertension, the leading cause being left heart failure with preserved (HFpEF) or reduced ejection fraction (HFmrEF, HFrEF), valvular heart disease and, less commonly, congenital heart disease. The presence of pulmonary hypertension is associated with increased symptom burden and poorer outcome across the spectrum of left heart disease. Differentiating between group 1 pulmonary hypertension with cardiac comorbidities and PH-LHD, especially due to HFpEF, is a particular challenge. Therapeutically, no general recommendation for the use of PDE5 inhibitors in HFpEF-associated CpcPH can be made at this time. There is currently no reliable rationale for the use of PAH drugs in IpcPH, nor is therapy with endothelin receptor antagonists or prostacyclin analogues recommended for all forms of PH-LHD.


Asunto(s)
Cardiopatías , Insuficiencia Cardíaca , Hipertensión Pulmonar , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/etiología , Insuficiencia Cardíaca/complicaciones , Volumen Sistólico , Cardiopatías/complicaciones , Resistencia Vascular
2.
Artículo en Alemán | MEDLINE | ID: mdl-27188620

RESUMEN

BACKGROUND AND OBJECTIVE: Percutaneous coronary interventions (PCIs) are increasingly being performed in the treatment of coronary artery disease. The aim of this study is to describe the frequency of PCIs by age, sex, type, and setting of the intervention in Germany. METHODS: Based on routine data of more than eight million insurants from three statutory health insurance funds, quarterly sex- and age-specific intervention rates were calculated between 2004 and 2012. Moreover, inpatient PCIs were subdivided into PCIs with conventional bare metal stents (BMS) and PCIs with drug-eluting stents (DES). Rates were age- and sex-standardized according to the age and sex distribution of the particular years in Germany. RESULTS: Standardized rates increased from 277.3 to 382.2 per 100,000 person-years between 2004 and 2012. The intervention rate was three times higher in men than in women. The relative increase in the overall rate and in the rate of PCI with DES during the study period were 38 and 548 % respectively, whereas the rate of PCI with BMS declined by 48 %. Of all PCIs, 7-11 % were outpatient PCIs during the study period. CONCLUSIONS: PCIs are increasingly being performed in Germany, particularly PCI with DES. The frequency of PCI with BMS implantation is decreasing. Sex-specific differences in the frequency of PCI go beyond differences that would have been expected because of a differing morbidity profile. Our analyses indicate that comparatively few outpatient PCIs are performed.


Asunto(s)
Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/cirugía , Intervención Coronaria Percutánea/estadística & datos numéricos , Intervención Coronaria Percutánea/tendencias , Pautas de la Práctica en Medicina/estadística & datos numéricos , Pautas de la Práctica en Medicina/tendencias , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Alemania/epidemiología , Humanos , Lactante , Recién Nacido , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Distribución por Sexo , Revisión de Utilización de Recursos , Adulto Joven
3.
J Mater Sci Mater Med ; 24(1): 241-55, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23053808

RESUMEN

In-stent restenosis is still an important issue and stent thrombosis is an unresolved risk after coronary intervention. Biodegradable stents would provide initial scaffolding of the stenosed segment and disappear subsequently. The additive manufacturing technology Selective Laser Melting (SLM) enables rapid, parallel, and raw material saving generation of complex 3- dimensional structures with extensive geometric freedom and is currently in use in orthopedic or dental applications. Here, SLM process parameters were adapted for poly-L-lactid acid (PLLA) and PLLA-co-poly-ε-caprolactone (PCL) powders to generate degradable coronary stent prototypes. Biocompatibility of both polymers was evidenced by assessment of cell morphology and of metabolic and adhesive activity at direct and indirect contact with human coronary artery smooth muscle cells, umbilical vein endothelial cells, and endothelial progenitor cells. γ-sterilization was demonstrated to guarantee safety of SLM-processed parts. From PLLA and PCL, stent prototypes were successfully generated and post-processing by spray- and dip-coating proved to thoroughly smoothen stent surfaces. In conclusion, for the first time, biodegradable polymers and the SLM technique were combined for the manufacturing of customized biodegradable coronary artery stent prototypes. SLM is advocated for the development of biodegradable coronary PLLA and PCL stents, potentially optimized for future bifurcation applications.


Asunto(s)
Estenosis Coronaria/prevención & control , Ácido Láctico , Rayos Láser , Polímeros , Stents , Materiales Biocompatibles , Células Cultivadas , Cromatografía en Gel , Humanos , Microscopía Electrónica de Rastreo , Microscopía Fluorescente , Músculo Liso Vascular/citología , Poliésteres
4.
Am J Cardiol ; 101(2): 139-43, 2008 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-18178395

RESUMEN

Recent studies emphasized the non-lipid-lowering effects of hydroxymethylglutaryl coenzyme A reductase inhibitors on endothelial function, inflammation, and platelet activation in patients with stable atherosclerosis. This study sought to evaluate the impact of statin pretreatment in patients with acute myocardial infarction (AMI) on level of systemic inflammation and myocardial perfusion. A total of 253 consecutive patients undergoing primary angioplasty on a native vessel within 12 hours of AMI were divided into a group with statin pretreatment (n = 86) and control patients (n = 167). Angiographic myocardial blush grade (MBG) after revascularization of the infarct-related artery was determined to evaluate myocardial perfusion. Statin pretreatment was associated with a lower frequency of increased C-reactive protein (>or=5 mg/L) on admission compared with the control group (48% vs 64%; p = 0.019). The frequency of normal perfusion (MBG 3) was higher in the statin-pretreatment group than the control group (45% vs 26%, respectively; p <0.001). Statin pretreatment was an independent predictor of normal myocardial perfusion (MBG 3; odds ratio 2.53, 95% confidence interval 1.15 to 9.53, p = 0.022) in addition to age

Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Angioplastia Coronaria con Balón , Proteína C-Reactiva , Angiografía Coronaria , Circulación Coronaria , Esquema de Medicación , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Masculino , Persona de Mediana Edad , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/terapia , Cuidados Preoperatorios , Resultado del Tratamiento
5.
Int J Cardiol ; 272S: 53-62, 2018 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-30527996

RESUMEN

In the summer of 2016, delegates from the German Society of Cardiology (DGK), the German Respiratory Society (DGP), and the German Society of Pediatric Cardiology (DGPK) met in Cologne, Germany, to define consensus-based practice recommendations for the management of patients with pulmonary hypertension (PH). These recommendations were built on the 2015 European Pulmonary Hypertension guidelines, aiming at their practical implementation, considering country-specific issues, and including new evidence, where available. To this end, a number of working groups was initiated, one of which was specifically dedicated to PH associated with left heart disease. In this context, the European Guidelines point out that the drugs currently approved to treat patients with PAH (prostanoids, endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, sGC stimulators) have not sufficiently been investigated in other forms of PH. However, despite the lack of respective efficacy data, an uncritical use of targeted PAH drugs in patients with PH associated with left heart disease is currently observed at an increasing rate. This development is a matter of concern. On the other hand, PH is a frequent problem that is highly relevant for morbidity and mortality in patients with left heart disease. In that sense, the distinction between isolated post-capillary pulmonary hypertension (IpcPH) and combined post- and pre-capillary pulmonary hypertension (CpcPH) and their proper definition may be of particular relevance. The detailed results and recommendations of the working group on PH associated with left heart disease, which were last updated in the spring of 2018, are summarized in this article.


Asunto(s)
Conferencias de Consenso como Asunto , Insuficiencia Cardíaca/terapia , Hipertensión Pulmonar/terapia , Guías de Práctica Clínica como Asunto/normas , Disfunción Ventricular Izquierda/terapia , Alemania/epidemiología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/epidemiología , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/epidemiología , Disfunción Ventricular Izquierda/diagnóstico , Disfunción Ventricular Izquierda/epidemiología
6.
Atherosclerosis ; 192(2): 413-20, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-16837000

RESUMEN

While statin treatment may transiently mobilize endothelial progenitor cells (EPCs), the dose-dependent effects of a continuous statin therapy on EPCs in patients with chronic coronary artery disease (CAD) have not been analyzed. In 209 patients with angiographically documented CAD, 144 of which received 10-40 mg/day of statins for >8 weeks, the EPC number was determined by flow cytometry directly (CD34(+)/KDR(+), n=58) and after in vitro-culture (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled Ac-LDL (DiI-Ac-LDL(+))/lectin(+), n=209). EPC function was assessed by the formation of colony forming units (CFUs). Univariate analysis revealed that the dose of continuous statin therapy inversely correlated with the EPC number. Treatment with 40 mg/day significantly reduced EPC counts. Multivariate analysis unveiled the statin dose and extent of CAD as independent predictors of reduced EPC numbers. Conversely, obesity predicted increased counts, while CFU development was not detectable in all patients and augmented in females and smokers but not in statin-treated patients. Compared with matched controls, statin-treated patients showed significantly reduced absolute and relative EPC counts. In a prospective analysis, initiation of statin therapy significantly diminished the number of circulating and isolated EPCs after 3 but not after 1 month(s). Thus, the statin dose during chronic and continuous treatment independently predicts reduced numbers of circulating as well as isolated EPCs in patients with CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Células Endoteliales/citología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Células Madre/citología , Antígenos CD34/análisis , Recuento de Células , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Células Madre/efectos de los fármacos , Receptor 2 de Factores de Crecimiento Endotelial Vascular/sangre
7.
Thromb Haemost ; 98(6): 1329-34, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18064332

RESUMEN

Low-response to the P2Y12 adenosine diphosphate (ADP)-receptor antagonist clopidogrel was suggested to correspond to a higher incidence of stent thrombosis (ST). This prospective observational study assessed the capability of two platelet function assays, e.g. direct measurement of the phosphorylation status of vasodilator-stimulated phosphoprotein (VASP) and ADP-induced platelet aggregation for definition of the individual risk to develop ST. Ninety-nine patients with an elevated high risk to develop ST were enrolled. All patients received a dual antiplatelet therapy consisting of 100 mg aspirin and 75 mg clopidogrel during an observation period of six months. Flow cytometry of VASP phosphorylation and densitometrically-determined measurement of ADP-induced platelet aggregation was performed 72-96 hours after stent implantation. These data were related to angiographically confirmed ST. Nine patients suffered from angiographically confirmed ST (9.1%). The meanVASP-platelet reactivity indices (VASP-PRI) and values for ADP-induced platelet aggregation in the ST group were significantly higher (60.8 +/- 13.0 and 60.9 +/- 13.1, respectively) compared to patients without ST (41.3 +/- 14.0 and 50.8 +/- 14.4, P < 0.001 vs. 0.048, respectively). There was a fair correlation between both methods using non-linear regression analysis (r = 0.332). In a multivariate analysis, VASP was the only independent predictor of ST and was superior to previously identified angiographic parameters. Receiver- operator characteristic (ROC) curve analysis revealed a cut-off value for VASP-PRI of <48% to be associated with low risk of ST. In conclusion, determination of VASP phosphorylation is superior to conventional platelet aggregometry and angiographic parameters for assessing the risk of ST. Patients with a VASP-PRI >48% seem to have a significantly increased risk.


Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Moléculas de Adhesión Celular/sangre , Proteínas de Microfilamentos/sangre , Fosfoproteínas/sangre , Inhibidores de Agregación Plaquetaria/uso terapéutico , Agregación Plaquetaria , Pruebas de Función Plaquetaria , Stents , Trombosis/diagnóstico , Adenosina Difosfato , Anciano , Angioplastia Coronaria con Balón/instrumentación , Aspirina/uso terapéutico , Clopidogrel , Angiografía Coronaria , Quimioterapia Combinada , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Fosforilación , Pruebas de Función Plaquetaria/métodos , Valor Predictivo de las Pruebas , Estudios Prospectivos , Curva ROC , Reproducibilidad de los Resultados , Proyectos de Investigación , Medición de Riesgo , Factores de Riesgo , Sensibilidad y Especificidad , Trombosis/sangre , Trombosis/diagnóstico por imagen , Trombosis/etiología , Trombosis/prevención & control , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento
8.
Am J Cardiol ; 100(9): 1347-52, 2007 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-17950788

RESUMEN

Patients with metabolic syndrome (MS) are at increased risk for cardiovascular events. Although the number of patients with MS requiring coronary revascularization is increasing rapidly, the impact of MS on clinical events and restenosis in patients who undergo stent placement is not well defined. Seven hundred thirty-four consecutive patients with 734 de novo coronary lesions (<50 mm lesion length, reference vessel diameter <3.5 mm) were enrolled in this study. Four hundred thirty-seven patients were treated with bare-metal stents, and 297 patients were treated with sirolimus-eluting stents. Patients with bifurcation lesions, left main lesions, and ST-segment-elevation myocardial infarctions were excluded from the study. Patients were categorized into 3 groups: those with (1) diabetes mellitus (DM), (2) MS without DM, and (3) no MS and no DM. MS was defined according to American Heart Association and National Heart, Lung, and Blood Institute criteria (the presence of > or =3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, and increased fasting glucose). Clinical follow-up was performed for > or =1 year (mean 27.5 +/- 18.1 months). One hundred sixty-four patients (22%) had DM, 180 patients (25%) had MS without DM, and 390 patients (53%) had no MS and no DM. Baseline clinical and angiographic parameters were comparable among the 3 groups, including lesion length and reference vessel diameter. In patients treated with bare-metal stents, the rates of major adverse cardiac events (MACEs) at 12 months were 14% in patients without DM or MS, 18% in those with MS but no DM, and 33% in those with DM (p = 0.046). In patients treated with sirolimus-eluting stents, the MACE rates were 3% in patients without DM or MS, 4% in those with MS, and 13% in those with DM (p = 0.034). DM (odds ratio 2.14, 95% confidence interval 1.48 to 3.07, p <0.001) and bare-metal stent (odds ratio 2.51, 95% confidence interval 1.49 to 4.22, p <0.001) implantation were independent predictors of MACEs during follow-up, whereas MS was not predictive. Similarly, MS was not a predictor of target lesion revascularization. In conclusion, patients with MS did not have an increased risk for target lesion revascularization or a greater MACE rate compared with control patients during a 12 month follow-up period after bare-metal or drug-eluting stent placement. In contrast, DM is associated with significantly increased event rates.


Asunto(s)
Angioplastia Coronaria con Balón , Enfermedad Coronaria/terapia , Reestenosis Coronaria/epidemiología , Angiopatías Diabéticas/terapia , Síndrome Metabólico/epidemiología , Síndrome Coronario Agudo/terapia , Anciano , Angiografía Coronaria , Reestenosis Coronaria/diagnóstico por imagen , Angiopatías Diabéticas/epidemiología , Femenino , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Sirolimus/administración & dosificación , Stents
9.
AJR Am J Roentgenol ; 188(2): 361-9, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17242243

RESUMEN

OBJECTIVE: The objective of our study was to determine the accuracy of 16-MDCT for evaluation of stent patency and in-stent stenosis in venous coronary bypass grafts. SUBJECTS AND METHODS: Fourteen patients who had previous stent placements in stenosed venous coronary bypass grafts underwent contrast-enhanced MDCT of the heart (collimation, 16 x 0.75 mm; 120 kV; 550 mAs(eff)) and invasive coronary angiography. A total of 20 stents were evaluated: Vessel and stent diameters proximal to, distal to, and at various sites inside the stent were measured on both techniques, and Bland-Altman plots and correlations were calculated. Image noise and image quality were also assessed applying a Student's t test for data comparison of image noise. RESULTS: All 20 bypass stents were correctly classified as patent. Vessel diameters outside the stent showed an excellent correlation (r = 0.90) and in-stent diameters showed a good correlation (r = 0.72), with lower values for MDCT due to blooming artifacts. All significant in-stent stenoses were correctly classified. CONCLUSION: In patients suspected of bypass in-stent stenosis, 16-MDCT may be considered as a valuable alternative to conventional angiography for evaluating bypass patency and in-stent stenosis.


Asunto(s)
Prótesis Vascular/efectos adversos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/instrumentación , Oclusión de Injerto Vascular/diagnóstico por imagen , Oclusión de Injerto Vascular/etiología , Stents/efectos adversos , Tomografía Computarizada por Rayos X/métodos , Cateterismo Cardíaco , Angiografía Coronaria , Puente de Arteria Coronaria/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Implantación de Prótesis/efectos adversos , Implantación de Prótesis/métodos , Tomografía Computarizada por Rayos X/instrumentación , Resultado del Tratamiento
10.
Coron Artery Dis ; 18(8): 601-6, 2007 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18004109

RESUMEN

BACKGROUND: Patients with metabolic syndrome (MetS) are at increased risk of cardiovascular events. The impact of MetS on clinical events and restenosis after drug-eluting stent placement is not well defined. METHODS: Two hundred and seventy-four consecutive patients with 298 de-novo coronary lesions (<50 mm lesion length, reference diameter<3.5 mm) successfully treated with sirolimus-eluting stents (SES) were enrolled in the study. Bifurcation lesions, left main lesions and ST-segment elevation myocardial infarcts were excluded. Patients were categorized into three groups: (i) diabetes, (ii) MetS without diabetes, (iii) controls without MetS or diabetes. MetS was defined as presence of > or =3 of the following criteria: obesity, hypertension, hypertriglyceridemia, low high-density lipoprotein cholesterol, raised fasting glucose. RESULTS: One hundred and twenty-one patients (44%) with 134 lesions had neither MetS nor diabetes, 84 patients (31%) with 89 lesions had MetS without diabetes and 69 patients (25%) with 75 lesions had diabetes. Baseline angiographic parameters were comparable between the three groups. Clinically driven target lesion revascularization rates and major adverse cardiac event rates at 12 months were 1, 1, 7% (P=0.039) and 3, 6 and 14% (P=0.032), respectively, for controls, patients with MetS/no diabetes and diabetic patients. Follow-up angiography at 6 months demonstrated late loss in lesion, which was 0.10+/-0.33 mm in the controls, 0.10+/-0.20 mm in patients with MetS/no diabetes and 0.36+/-0.66 mm in diabetic patients (P=0.009). CONCLUSION: MetS without diabetes does not result in an increase in target lesion revascularization, major adverse cardiac event rates or angiographic late loss compared with control patients after implantation of SES in de-novo coronary lesions.


Asunto(s)
Angiografía Coronaria , Síndrome Metabólico/fisiopatología , Sirolimus/administración & dosificación , Stents , Anciano , Sistemas de Liberación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad
11.
Atherosclerosis ; 186(1): 177-83, 2006 May.
Artículo en Inglés | MEDLINE | ID: mdl-16140308

RESUMEN

This study sought to evaluate the relation between C-reactive protein (CRP) on admission of patients with acute myocardial infarction (AMI) and myocardial perfusion as defined by postintervention angiographic myocardial blush grade (MBG) and their impact on subsequent mortality. The patient population comprised 191 consecutive patients with AMI undergoing PTCA within 12h of symptom onset on a native vessel. Patients were divided based on the CRP level on admission (Rolf Greiner BioChemica, Germany, cutpoint for the assay CRP: 5mg/l) into a group with elevated CRP (>or=5mg/l) and a group with normal CRP. Angiographic myocardial blush grade (MBG) after revascularization of the infarct-related artery was determined to evaluate myocardial reperfusion. Revascularization of the infarct-related artery was successful in 176 (92.6%) patients. The frequency of impaired perfusion (MBG 0-2) was higher in the elevated CRP group than in the normal CRP group (74.5% versus 59.7%, respectively, p=0.046). Elevated CRP on admission was an independent predictor of impaired myocardial perfusion (MBG 0-2, OR 1.92, 95% CI 1.02-4.01, p=0.042) in addition to age >70 years. Elevated CRP (OR 2.64, 95% CI 1.26-5.53, p=0.009) and MBG 0-2 (OR 4.58; 95% 1.73-12.20, p=0.002) were independent predictors of mortality during a 22.4+/-15.3 months follow-up in addition to heart rate on admission >100 beats/min (OR 3.07; 95% CI 1.30-7.25, p=0.009). In sequential Cox models, the predictive power of clinical data and MBG for mortality (model chi-squared 18.3) was strengthened by the inclusion of CRP levels (model chi-squared 24.3). In conclusion, there is a relation between elevated admission CRP and impaired reperfusion in the myocardium subtended to the infarct-related artery. The combination of clinical data, myocardial reperfusion levels after primary angioplasty for AMI and admission CRP increases the predictive value for subsequent survival.


Asunto(s)
Proteína C-Reactiva/metabolismo , Circulación Coronaria/fisiología , Electrocardiografía , Infarto del Miocardio/sangre , Anciano , Biomarcadores/sangre , Angiografía Coronaria , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Infarto del Miocardio/fisiopatología , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia
12.
Am J Cardiol ; 98(8): 1022-7, 2006 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-17027564

RESUMEN

Although polymer coating of coronary stents enables sufficient loading and release of incorporated drugs, it has also been associated with potentially negative effects. This study compared the clinical, angiographic, and intravascular ultrasound (IVUS) outcomes of patients treated with polymer- versus nonpolymer-based paclitaxel-eluting stents (PESs). Sixty-five consecutive patients (70 de novo lesions) treated with polymer-based PESs (TAXUS, 1 microg/mm2 of paclitaxel; Boston Scientific Corp.) and 65 consecutive patients (65 de novo lesions) treated with nonpolymer-based PESs (V-Flex Plus, 2.7 microg/mm2 of paclitaxel; Cook, Inc.) were enrolled in the study. Six-month angiographic follow-up was performed on 54 lesions of the polymer-based PES group and 51 lesions of the nonpolymer-based PES group. IVUS at angiographic follow-up was performed in 61 of the first 70 included lesions. At 6-month IVUS follow-up, mean intimal hyperplasia cross-sectional area was 2.36 +/- 1.60 mm2 in the nonpolymer-based PES group versus 0.62 +/- 0.41 mm2 in the polymer-based PES group (p = 0.003). Implantation of polymer-based PESs resulted in significantly lower in-stent late lumen loss (0.22 +/- 0.27 vs 0.74 +/- 0.61 mm, respectively, p <0.001). In-stent binary restenosis rate was 5% versus 20%, respectively (p <0.001). Target lesion revascularization rate was 9% after implantation of polymer-based PES versus 18% (p = 0.128) after implantation of nonpolymer-based PES, and the major adverse cardiac event rate was 9% versus 23%, respectively (p = 0.032). In conclusion, polymer-based PESs result in superior angiographic and IVUS follow-up findings compared with nonpolymer-based PESs.


Asunto(s)
Estenosis Coronaria/terapia , Paclitaxel/administración & dosificación , Stents , Moduladores de Tubulina/administración & dosificación , Angiografía Coronaria , Estenosis Coronaria/mortalidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Tasa de Supervivencia , Resultado del Tratamiento , Ultrasonografía Intervencional
13.
Cardiovasc Res ; 62(1): 212-22, 2004 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-15023568

RESUMEN

OBJECTIVE: The aim of the study was to analyze whether cadherin- and Rho-family GTPases-mediated dynamic rearrangement of cell-cell adhesion play an important role during human arterial smooth muscle cell (haSMC) migration. METHODS: Expression patterns of N-cadherin and beta-catenin were analyzed in a domestic pig restenosis model after 14, 28, and 90 days as well as in quiescent and migratory haSMCs in vitro. N-cadherin expression was upregulated by transient sense; downregulation was induced by antisense transfection. For functional inhibition, antibody GC-4 was used. Cell migration was quantified using Boyden chamber assays. Regulation of RhoA GTPase was tested by assessment of RhoA activity. RESULTS: In vivo analysis of N-cadherin expression in a porcine restenosis model revealed downregulation in the neointima after 14 days. After 28 days, N-cadherin expression was slightly restored, while after 90 days, no difference between medial and neointimal expression was detectable. beta-Catenin levels remained unchanged during the whole period. According to the in vivo situation, N-cadherin was significantly downregulated in migratory haSMCs compared to quiescent cells in vitro. After N-cadherin overexpression, haSMC migration was reduced by 87% (P<0.001). By contrast, inhibition of N-cadherin in quiescent haSMCs by GC-4 increased the migratory potential by 87% (P<0.01). In haSMCs overexpressing N-cadherin, a significant upregulation of RhoA activity was demonstrated, while RhoA activity was blocked by GC-4. CONCLUSIONS: These results indicate that the regulation of haSMC attachment by N-cadherins is essential for haSMC migration. Modification of N-cadherin expression and activity induces RhoA signaling with relevance for the reorganization of the actin cytoskeleton.


Asunto(s)
Cadherinas/análisis , Reestenosis Coronaria/metabolismo , Músculo Liso/metabolismo , Túnica Íntima/metabolismo , Proteína de Unión al GTP rhoA/metabolismo , Animales , Anticuerpos Monoclonales/farmacología , Cadherinas/genética , Movimiento Celular , Proteínas del Citoesqueleto/metabolismo , Humanos , Inmunohistoquímica/métodos , Modelos Animales , Músculo Liso/patología , Neovascularización Patológica , Oligonucleótidos Antisentido/genética , Porcinos , Transactivadores/metabolismo , Transfección/métodos , beta Catenina
14.
Cardiovasc Res ; 54(3): 630-9, 2002 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12031709

RESUMEN

Migrating cells like coronary smooth muscle cells in restenosis change their cell shape and form cellular protrusions called filopodia. A prerequisite for filopodia formation is the rearrangement of the actin cytoskeleton. An essential role of the 78-kDa protein Moesin is described for Rho- and Rac-dependent assembly of actin filaments. In vivo Moesin is not observed in mature smooth muscle cells. The objective of this study was to demonstrate that Moesin is upregulated in migrating coronary smooth muscle cells during restenosis development. In vivo expression of Moesin was upregulated in neointimal coronary smooth muscle cells of dilated porcine coronary arteries compared to the undilated left circumflex coronary artery of the same swine. Concordant to these results Moesin expression was upregulated in migrating and invading human arterial smooth muscle cells in vitro analyzed by FACS, Western blotting and RT-PCR. In addition, the invasive potential of Moesin-positive Mel Im cells transfected with Moesin sense DNA increased by 28% as compared to mock-transfected control, whereas antisense transfected cells had a decreased invasive potential of 32%. Transfection of Moesin-negative HepG2 with Moesin sense cDNA increased the invasive potential by 43%. Finally, transfection of human arterial smooth muscle cells with Moesin sense cDNA caused an increased invasive potential of 30%. Transfection of haSMCs with antisense cDNA decreased the invasive potential by 37% in comparison to mock-transfected control. These results demonstrate for the first time an upregulation of Moesin expression in coronary smooth muscle cells of the neointima after arterial injury. The increased migrative and invasive potential of cells transfected with Moesin confirmed the functional role of Moesin in cell migration. This indicates an important role of Moesin during restenosis development.


Asunto(s)
Angioplastia Coronaria con Balón , Estenosis Coronaria/metabolismo , Proteínas de Microfilamentos/análisis , Túnica Íntima/metabolismo , Actinas/análisis , Animales , Biomarcadores/análisis , Movimiento Celular , Células Cultivadas , Estenosis Coronaria/patología , Vasos Coronarios , Citometría de Flujo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Modelos Animales , Músculo Liso Vascular/patología , Porcinos , Transfección
15.
Am J Cardiol ; 93(6): 760-2, 2004 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-15019887

RESUMEN

Treatment of in-stent restenosis remains a therapeutic challenge. Twenty-seven lesions with in-stent restenosis were treated with non-polymer-based paclitaxel-eluting stents. At 6-month follow-up, in-stent late loss was 0.44 +/- 0.54 mm and the restenosis rate was 20%, indicating effective treatment for reduction of recurrent restenosis.


Asunto(s)
Reestenosis Coronaria , Reestenosis Coronaria/terapia , Inhibidores de Crecimiento/administración & dosificación , Paclitaxel/administración & dosificación , Stents , Angiografía Coronaria , Reestenosis Coronaria/diagnóstico por imagen , Reestenosis Coronaria/patología , Europa (Continente) , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polímeros , Resultado del Tratamiento
16.
Am J Cardiol ; 92(9): 1015-9, 2003 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-14583349

RESUMEN

This study sought to analyze the evolution of myocardial perfusion during follow-up after primary angioplasty for acute myocardial infarction (AMI) and relate it to final left ventricular (LV) function. In 101 patients with a first AMI, angiographic myocardial blush grade (MBG) was analyzed immediately after intervention and at follow-up 7.5 +/- 5.6 months later. Cine ventriculography was performed at follow-up angiography to define LV function. Five patients had occluded stents or flow-limiting restenosis. In the remaining patients, myocardial perfusion at follow-up, as defined by MBG, was persistently abnormal in 19 patients (20%), had become normalized from previously abnormal MBG in 30 patients (31%), remained normal in 40 patients (42%), and deteriorated from normal to abnormal in 7 patients (7%). Patients with improvement of abnormal blush determined immediately after intervention to normal blush at follow-up (n = 30) compared with patients with persistently abnormal blush (n = 19) had a better LV ejection fraction at follow-up (53.7 +/- 11.1 vs. 37.4 +/- 9.7%, p <0.001). Evolution of MBG had a better predictive value for LV ejection fraction at follow-up than acute MBG only. Multivariate analysis proved evolution of MBG from AMI to follow-up to be an independent predictor of LV function (R(2) = 0.177, p <0.001) in addition to the initial size of jeopardized myocardium as defined by the sum of ST-segment elevation (R(2) = 0.138, p = 0.001) and infarct location (R(2) = 0.044, p = 0.033). In conclusion, tissue reperfusion after angioplasty for AMI is characterized by frequent improvement over time, as indicated by repeated MBG analysis. Patients with recovery of perfusion have better, final LV function.


Asunto(s)
Angioplastia Coronaria con Balón , Angiografía Coronaria , Circulación Coronaria/fisiología , Infarto del Miocardio/diagnóstico por imagen , Infarto del Miocardio/fisiopatología , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/terapia , Evaluación de Resultado en la Atención de Salud , Valor Predictivo de las Pruebas , Índice de Severidad de la Enfermedad , Volumen Sistólico/fisiología , Factores de Tiempo
17.
Am J Cardiol ; 94(12): 1548-50, 2004 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-15589014

RESUMEN

Intravascular ultrasound studies were performed at angiographic follow-up on 121 native coronary lesions treated with 1 bare metal stent (n = 50), high-dose dexamethasone-eluting stents (n = 18), non-polymer-based paclitaxel-eluting stents (n = 18), or sirolimus-eluting stents (n = 35). Paclitaxel- and sirolimus-eluting stents reduced mean intimal hyperplasia thickness compared with bare metal stents by 49% and 90% (p = 0.048 and p <0.001), respectively, whereas mean intimal hyperplasia thickness treated with dexamethasone-eluting stents was similar to those lesions treated with bare metal stents.


Asunto(s)
Vasos Coronarios/patología , Stents , Reestenosis Coronaria/etiología , Vasos Coronarios/diagnóstico por imagen , Dexametasona , Humanos , Hiperplasia , Paclitaxel , Diseño de Prótesis , Sirolimus , Stents/efectos adversos , Túnica Íntima/patología , Ultrasonografía Intervencional
18.
Am J Cardiol ; 94(2): 193-5, 2004 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-15246899

RESUMEN

This study evaluated the safety and efficacy of a dexamethasone-eluting stent with a special high dexamethasone-loading dose for treatment of de novo coronary lesions in 30 patients. Eight patients had in-stent restenosis (restenosis rate 31%) at 6-month follow-up, and the in-stent late lumen loss was 0.96 +/- 0.63 mm due to an average intimal hyperplasia area obstruction of 32 +/- 21%, indicating that high-dose dexamethasone-loaded stents do not significantly reduce neointimal proliferation.


Asunto(s)
Antiinflamatorios/administración & dosificación , Reestenosis Coronaria/prevención & control , Dexametasona/administración & dosificación , Stents , Adulto , Angiografía Coronaria , Reestenosis Coronaria/diagnóstico por imagen , Femenino , Humanos , Masculino , Proyectos Piloto , Diseño de Prótesis , Ultrasonografía Intervencional
19.
Invest Radiol ; 39(1): 27-33, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14701986

RESUMEN

RATIONALE AND OBJECTIVE: The aim of this study was to systematically compare the ability to assess the coronary artery lumen in the presence of coronary artery stents in multislice spiral CT (MSCT). METHODS: Ten different coronary artery stents were examined with 4- and 16-detector row MSCT scanners. For image reconstruction, a standard and a dedicated convolution kernel for coronary artery stent visualization were used. Images were analyzed regarding lumen visibility, intraluminal attenuation, and artifacts outside the stent lumen. Results were compared using repeated-measure analysis of variance. RESULTS: Depending on stent type, scanner hardware, and convolution kernel, artificial lumen narrowing ranged from 20% to 100%. The convolution kernel had the most significant influence on the visibility of the stent lumen. Artificial lumen narrowing and intraluminal attenuation changes decreased significantly using the dedicated convolution kernel. In general, most severe artifacts were caused by gold or gold-coated stents. CONCLUSIONS: Independent of the scanner hardware or dedicated convolution kernels, routine evaluation of most coronary artery stents is not yet feasible using MSCT.


Asunto(s)
Artefactos , Estenosis Coronaria/diagnóstico por imagen , Stents , Tomografía Computarizada Espiral , Análisis de Varianza , Angiografía Coronaria , Estenosis Coronaria/terapia , Diseño de Equipo , Humanos , Técnicas In Vitro
20.
Tissue Eng ; 8(2): 235-45, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12031113

RESUMEN

Transfection of primary cells and stem cells is a problem in the laboratory routine and further in tissue engineering and gene therapy. Most methods working effectively for cell lines in culture fail to transfect primary cells. Here we describe the use of the Nucleofector technology developed by amaxa biosystems. We were able to transfect primary human melanocytes, human coronary smooth muscle cells, human chondrocytes, and human mesenchymal stem cells with high efficiencies (28.9-45.3%). All primary cell types failed to be transfected satisfactorily by methods based on liposome-mediated transfection in our hands. The viability of the transfected cells varied between 11.2% and 75% in comparison to untreated cells. Only 200,000 cells per transfection sample were needed. In summary, this method presents an effective and fast mean for transfection of primary and stem cells demonstrated by four cell types which are only transfected with low efficiency by other methods.


Asunto(s)
Terapia Genética/métodos , Ingeniería de Tejidos/métodos , Transfección/métodos , Supervivencia Celular , Condrocitos/citología , Condrocitos/fisiología , Humanos , Melanocitos/citología , Melanocitos/fisiología , Mesodermo/fisiología , Músculo Liso Vascular/citología , Músculo Liso Vascular/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Madre/citología , Células Madre/fisiología , Transfección/instrumentación
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