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1.
Catheter Cardiovasc Interv ; 102(5): 823-833, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37668088

RESUMEN

BACKGROUND: Severely calcified coronary lesions present a particular challenge for percutaneous coronary intervention. AIMS: The aim of this randomized study was to determine whether coronary intravascular lithotripsy (IVL) is non-inferior to rotational atherectomy (RA) regarding minimal stent area (MSA). METHODS: The randomized, prospective non-inferiority ROTA.shock trial enrolled 70 patients between July 2019 and November 2021. Patients were randomly (1:1) assigned to undergo either IVL or RA before percutaneous coronary intervention of severely calcified coronary lesions. Optical coherence tomography was performed at the end of the procedure for primary endpoint analysis. RESULTS: The primary endpoint MSA was lower but non-inferior after IVL (mean: 6.10 mm2 , 95% confidence interval [95% CI]: 5.32-6.87 mm2 ) versus RA (6.60 mm2 , 95% CI: 5.66-7.54 mm2 ; difference in MSA: -0.50 mm2 , 95% CI: -1.52-0.52 mm2 ; non-inferiority margin: -1.60 mm2 ). Stent expansion was similar (RA: 0.83 ± 0.10 vs. IVL: 0.82 ± 0.11; p = 0.79). There were no significant differences regarding contrast media consumption (RA: 183.1 ± 68.8 vs. IVL: 163.3 ± 55.0 mL; p = 0.47), radiation dose (RA: 7269 ± 11288 vs. IVL: 5010 ± 4140 cGy cm2 ; p = 0.68), and procedure time (RA: 79.5 ± 34.5 vs. IVL: 66.0 ± 19.4 min; p = 0.18). CONCLUSION: IVL is non-inferior regarding MSA and results in a similar stent expansion in a random comparison with RA. Procedure time, contrast volume, and dose-area product do not differ significantly.


Asunto(s)
Aterectomía Coronaria , Enfermedad de la Arteria Coronaria , Litotricia , Calcificación Vascular , Humanos , Aterectomía Coronaria/efectos adversos , Aterectomía Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/terapia , Constricción Patológica , Estudios Prospectivos , Angiografía Coronaria/métodos , Resultado del Tratamiento , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/terapia
2.
Herz ; 45(Suppl 1): 95-104, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31209520

RESUMEN

BACKGROUND: Limited data exist on bioresorbable scaffolds (BRS) in patients with acute coronary syndrome (ACS). The aim of the present study was to evaluate novolimus-eluting BRS (DESolve) as interventional treatment for patients with ACS, and to compare its 12-month outcomes with the everolimus-eluting bioresorbable scaffolds (Absorb). METHODS: In this retrospective study, patients with ACS (including unstable angina pectoris, ST-segment elevation myocardial infarction, or non-ST-segment elevation myocardial infarction) treated with either the Absorb or the DESolve BRS were evaluated in a 1:1 matched-pair analysis. Major adverse cardiac events (MACE), including death, myocardial infarction, and target lesion revascularization, were evaluated as a major endpoint. The occurrence of scaffold thrombosis was also assessed. RESULTS: A total of 102 patients were eligible for this analysis. The rate of MACE at 12 months was comparable between the Absorb and the DESolve group (8.3% vs. 6.8%, p = 0.738). The occurrence of target lesion revascularization (6.2% vs. 4.7%; p = 0.700) and scaffold thrombosis (4.1% vs. 2.1%; p = 0.580) was comparable as well. All instances of scaffold thrombosis occurred within 30 days of the index procedure. CONCLUSION: In this study, similar 12-month event rates were observed for both BRS types after implantation for the treatment of ACS.


Asunto(s)
Síndrome Coronario Agudo , Fármacos Cardiovasculares , Enfermedad de la Arteria Coronaria , Intervención Coronaria Percutánea , Implantes Absorbibles , Síndrome Coronario Agudo/cirugía , Everolimus , Humanos , Macrólidos , Diseño de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento
3.
Anaesthesist ; 69(2): 108-116, 2020 02.
Artículo en Alemán | MEDLINE | ID: mdl-31802173

RESUMEN

BACKGROUND: Despite an increasing incidence of patients suffering from acute coronary syndrome (ACS) under simultaneous treatment with direct oral anticoagulants (DOAC), neither sufficient scientific data nor uniform guidelines for the anticoagulation treatment of these patients are currently available. OBJECTIVE: The aim of this study was to determine the current practice of preclinical treatment of ACS in patients under DOAC treatment. MATERIAL AND METHODS: An internet and paper-based survey of emergency physicians, specialists of internal medicine, anesthesiologists, emergency and intensive care physicians was performed concerning the prehospital treatment of ACS in patients under long-term DOAC treatment. RESULTS: Overall, 284 questionnaires were answered. Substantial differences in the current treatment of ACS under long-term DOAC therapy were identified. While 39% of the respondents stated that they administer a combination treatment of heparin and acetylsalicylic acid (ASA), 36% renounced the administration of heparin. If a dose reduction was performed, 71% answered that they reduce the heparin dosage. Also, in cases of ST-segment elevation myocardial infarction 48% of the physicians renounced the administration of heparin. CONCLUSION: In Germany there is currently a heterogeneous practice of emergency treatment of ACS patients under DOAC therapy with respect to the administration of heparin and ASA. Therefore, guidelines of the specialist medical societies should address the prehospital emergency anticoagulation management of ACS in patients under therapy with DOAC, which correspond to the needs of patients and emergency physicians.


Asunto(s)
Síndrome Coronario Agudo/etiología , Síndrome Coronario Agudo/terapia , Anticoagulantes/efectos adversos , Anticoagulantes/administración & dosificación , Servicios Médicos de Urgencia , Alemania , Heparina/administración & dosificación , Heparina/efectos adversos , Humanos
4.
Herz ; 43(8): 759-770, 2018 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-30328479

RESUMEN

In recent years it has been observed with increasing interest that there is a group of patients with electrocardiographic and laboratory features of myocardial infarction (MI) but no obstructive coronary artery disease (<50% diameter stenosis). For this entity the term myocardial infarction with non-obstructive coronary arteries (MINOCA) has been coined. The prevalence of MINOCA is estimated to be 6-9% among patients diagnosed with MI and it is more common in women than men as well as in patients presenting with NSTEMI than in those presenting with STEMI. The MINOCA is a working diagnosis that requires a further diagnostic work-up by invasive techniques, such as intravascular ultrasound (IVUS) and optical coherence tomography (OCT) or non-invasive imaging with cardiac magnetic resonance imaging (CMRI). When it is ascertained that obstructive coronary artery disease has not been inadvertently overlooked, other coronary disorders, such as plaque rupture or erosion, thrombosis, dissection, spasms or microvascular dysfunction should be evaluated. Furthermore, myocarditis or tako-tsubo cardiomyopathy should be excluded by CMRI as non-coronary causes. The further treatment and prognosis of patients with MINOCA depend on the underlying cause and the final diagnosis.


Asunto(s)
Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Cardiomiopatía de Takotsubo , Angiografía Coronaria , Vasos Coronarios , Femenino , Humanos , Masculino
5.
Internist (Berl) ; 59(9): 981-992, 2018 09.
Artículo en Alemán | MEDLINE | ID: mdl-29978350

RESUMEN

BACKGROUND: Approximately 40-50% of patients with cryptogenic stroke have a patent foramen ovale (PFO). A concomitant atrial septal aneurysm aggravates the risk of recurrent stroke. OBJECTIVE: The most important changes regarding the evidence for interventional closure of a PFO in patients with cryptogenic stroke are described. This includes the prerequisites for making a diagnosis and the indications for interventional treatment. The article also provides an overview about platelet aggregation inhibitor treatment with and without oral anticoagulation. CURRENT DATA: The balance between benefits and risks of interventional versus pharmaceutical treatment in patients with cryptogenic stroke and PFO has so far not been sufficiently proven. In 2017 two prospective randomized trials (CLOSE and REDUCE) and the long-term follow-up results of the RESPECT study were published, followed by the results of the DEFENSE-PFO study in 2018. A better assessment of the weighing up of the treatment options can now be made. All four studies showed that the interventional treatment of PFO is superior to pharmaceutical treatment alone for patients with cryptogenic stroke under 60 years of age. CONCLUSION: There was a significant reduction in the incidence of recurrent stroke in patients with interventional PFO closure compared with pharmaceutical treatment. The complication rate of PFO closure is very low and younger patients (<60 years) in particular benefit from PFO closure.


Asunto(s)
Foramen Oval Permeable , Dispositivo Oclusor Septal , Accidente Cerebrovascular , Foramen Oval Permeable/tratamiento farmacológico , Foramen Oval Permeable/cirugía , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Recurrencia , Accidente Cerebrovascular/prevención & control , Resultado del Tratamiento
6.
Herz ; 42(2): 211-228, 2017 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-28233037

RESUMEN

Acute coronary syndrome without persistent ST-segment elevation (non-ST segment elevation myocardial infarction and instable angina pectoris NSTEMI-ACS) is common and is associated with a high mortality. In addition to 12-channel echocardiograph (ECG) assessment, measurement of cardiac troponins I and T are important for risk stratification and diagnosis. The introduction of high-sensitivity cardiac troponin assays and their implementation into clinical practice has influenced risk stratification and treatment of these patients. Additional diagnostic validation must supplement routine clinical chemistry testing following the initial measurement to distinguish between different possible causes of troponin elevation above the 99th percentile. The time point for the additional troponin measurement depends on the different protocols and troponin assays and is stipulated in the current guidelines. The use of both 1­hour and 3­hour protocols together with the clinical presentation and work-up of possible differential diagnoses provide optimal care of patients. Patients who test positive for troponin dynamics should undergo invasive diagnostics and treatment within 24 h of presentation and within 2 h is recommended for unstable patients. Clopidogrel is indicated only in patients requiring oral anticoagulation.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/terapia , Cuidados Críticos/métodos , Revascularización Miocárdica/métodos , Troponina I/sangre , Troponina T/sangre , Síndrome Coronario Agudo/sangre , Biomarcadores/sangre , Diagnóstico Diferencial , Medicina Basada en la Evidencia , Humanos , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/complicaciones , Infarto del Miocardio con Elevación del ST/diagnóstico , Resultado del Tratamiento
7.
Herz ; 42(1): 51-57, 2017 Feb.
Artículo en Alemán | MEDLINE | ID: mdl-27255115

RESUMEN

Coronary computed tomography angiography (cCTA) has been established for the non-invasive diagnosis of coronary artery disease (CAD). Previous studies demonstrated the high diagnostic accuracy of cCTA, particularly for ruling out CAD. As a known limitation of cCTA a large number of visually significant coronary stenoses are found to be hemodynamically not relevant by invasive fractional flow reserve (FFR). CT-based FFR (CT-FFR) builds on recent advances in computational fluid dynamics and image simulation techniques. Along with CT myocardial perfusion imaging, CT-FFR is a promising approach towards a more accurate estimation of the hemodynamic relevance of coronary artery stenoses. CT-FFR is derived from regular CT datasets without additional image acquisitions, contrast material, or medication. Two CT-FFR techniques can be differentiated. The initial method requires external use of supercomputers and has gained approval for clinical use in the USA. Furthermore, a prototype-software has been introduced which is less computationally demanding via integration of reduced-order models for on-site calculation of CT-FFR. The present article reviews these methods in the context of available study results and meta-analyses. Furthermore, limitations and future concepts of CT-FFR are discussed.


Asunto(s)
Angina Estable/diagnóstico , Angina Estable/fisiopatología , Velocidad del Flujo Sanguíneo , Angiografía por Tomografía Computarizada/métodos , Angiografía Coronaria/métodos , Reserva del Flujo Fraccional Miocárdico , Medicina Basada en la Evidencia , Humanos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
8.
Exp Eye Res ; 143: 75-88, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26450656

RESUMEN

The aim of this study was to develop a novel in vivo corneal model of fibrosis in dogs utilizing alkali burn and determine the ability of suberanilohydroxamic acid (SAHA) to inhibit corneal fibrosis using this large animal model. To accomplish this, we used seven research Beagle dogs. An axial corneal alkali burn in dogs was created using 1 N NaOH topically. Six dogs were randomly and equally assigned into 2 groups: A) vehicle (DMSO, 2 µL/mL); B) anti-fibrotic treatment (50 µM SAHA). The degree of corneal opacity, ocular health, and anti-fibrotic effects of SAHA were determined utilizing the Fantes grading scale, modified McDonald-Shadduck (mMS) scoring system, optical coherence tomography (OCT), corneal histopathology, immunohistochemistry (IHC), and transmission electron microscopy (TEM). The used alkali burn dose to produce corneal fibrosis was well tolerated as no significant difference in mMS scores between control and treatment groups (p = 0.89) were detected. The corneas of alkali burned dogs showed significantly greater levels of α-smooth muscle actin, the fibrotic marker, than the controls (p = 0.018). Total corneal thickness of all dogs post-burn was significantly greater than baseline OCT images irrespective of treatment (p = 0.004); TEM showed that alkali burned corneas had significantly greater minimum and maximum interfibrillar distances than the controls (p = 0.026, p = 0.018). The tested topical corneal alkali burn dose generated significant opacity and fibrosis in dog corneas without damaging the limbus as evidenced by histopathology, IHC, TEM, and OCT findings, and represents a viable large animal corneal fibrosis in vivo model. Additional in vivo SAHA dosing studies with larger sample size are warranted.


Asunto(s)
Quemaduras Químicas/patología , Córnea/patología , Enfermedades de la Córnea/patología , Modelos Animales de Enfermedad , Actinas/metabolismo , Animales , Biomarcadores/metabolismo , Quemaduras Químicas/tratamiento farmacológico , Quemaduras Químicas/metabolismo , Córnea/metabolismo , Enfermedades de la Córnea/tratamiento farmacológico , Enfermedades de la Córnea/metabolismo , Perros , Quemaduras Oculares/inducido químicamente , Femenino , Fibrosis , Inhibidores de Histona Desacetilasas/uso terapéutico , Ácidos Hidroxámicos/uso terapéutico , Inmunohistoquímica , Hidróxido de Sodio/toxicidad , Tomografía de Coherencia Óptica , Vorinostat
9.
Internist (Berl) ; 57(4): 304-16, 2016 Apr.
Artículo en Alemán | MEDLINE | ID: mdl-26902868

RESUMEN

BACKGROUND: Transcatheter aortic valve implantation (TAVI) has gained importance in recent years for the treatment of symptomatic aortic stenosis in Germany. OBJECTIVE: This article discusses the indications, the procedure itself and safety issues in TAVI. MATERIAL AND METHODS: Randomized controlled trials, registry studies, guidelines and expert recommendations are discussed. RESULTS: Inoperable patients as well as patients ≥ 75 years with a high perioperative risk and patients ≥ 85 years should primarily be treated by TAVI. The decision must be made following discussions in a heart team. If no contraindications are detected the TAVI procedure should be performed via the transfemoral approach with the patient under conscious sedation. In recent years there has been a significant reduction in complication rates. CONCLUSION: In Germany TAVI is the standard of care for surgical high-risk and inoperable patients with aortic valve stenosis.


Asunto(s)
Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/cirugía , Cardiología/normas , Prótesis Valvulares Cardíacas/normas , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Reemplazo de la Válvula Aórtica Transcatéter/normas , Medicina Basada en la Evidencia , Alemania , Humanos , Guías de Práctica Clínica como Asunto , Cuidados Preoperatorios/normas , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
10.
Herz ; 39(8): 913-8, 2014 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-25406330

RESUMEN

One of the most important treatment principles in interventional cardiology relies on myocardial revascularization by percutaneous coronary intervention (PCI) or surgical placement of coronary artery bypass grafts (CABG). However, in order to apply these principles effectively, it is important to identify patients who require revascularization. Consequently, the appropriate method has to be selected to effectively restore blood flow. Patients will only benefit from the interventional or surgical procedures when those revascularization measures that can cause more harm than good are avoided. In the new European Society of Cardiology and European Association for Cardio-Thoracic Surgery (ESC/EACTS) guidelines on myocardial revascularization some new aspects will be addressed.


Asunto(s)
Cardiología/normas , Puente de Arteria Coronaria/normas , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/cirugía , Técnicas de Diagnóstico Cardiovascular/normas , Selección de Paciente , Intervención Coronaria Percutánea/normas , Europa (Continente) , Humanos
11.
Herz ; 39(6): 685-91, 2014 Sep.
Artículo en Alemán | MEDLINE | ID: mdl-25070211

RESUMEN

Acute myocardial infarction was one of the most common causes of death in Germany in 2011. According to the guidelines of the European Society for Cardiology, systemic fibrinolysis and primary percutaneous coronary intervention (PCI) are the methods of choice for acute treatment. Primary PCI should be given priority due to its superiority. The transradial access should be preferred due to the lower bleeding complication rate. In the selection of stents the new generation of drug-eluting stents (DES) are superior to the first generation of bare metal stents (BMS). It has now been demonstrated that the incident rates of DES (e.g. mortality, target vessel revascularization, early and late stent thrombosis and myocardial infarction) are significantly lower. For bioresorbable scaffolds (BRS) long-term results for the use in treatment of ST-elevation myocardial infarction (STEMI) are not yet available but initial results are very promising. However, the selection of a stent needs to be done on an individual basis in order to do justice to all aspects. Data with respect to thrombectomy in acute treatment are heterogeneous. Currently, a thorough consideration of all aspects is necessary because thrombus aspiration can also be associated with an increased rate of incidents. In a state of hemodynamic stability only so-called culprit lesions should currently be treated with a stent. Elective interventions on further stenoses should be carried out after consideration of individual factors and if necessary evaluation of the hemodynamic relevance.


Asunto(s)
Prótesis Vascular , Estenosis Coronaria/cirugía , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea/instrumentación , Ajuste de Prótesis/métodos , Stents , Trombectomía/instrumentación , Terapia Combinada/instrumentación , Terapia Combinada/métodos , Estenosis Coronaria/complicaciones , Humanos , Infarto del Miocardio/etiología , Intervención Coronaria Percutánea/métodos , Trombectomía/métodos
12.
J Cell Mol Med ; 15(1): 52-62, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19941631

RESUMEN

Recently, we demonstrated that a fully differentiated tissue developed on a ventricular septal occluder that had been implanted due to infarct-related septum rupture. We suggested that this tissue originated from circulating stem cells. The aim of the present study was to evaluate this hypothesis and to investigate the physiological differentiation and transdifferentiation potential of circulating stem cells. We developed an animal model in which a freely floating membrane was inserted into each the left ventricle and the descending aorta. Membranes were removed after pre-specified intervals of 3 days, and 2, 6 and 12 weeks; the newly developed tissue was evaluated using quantitative RT-PCR, immunohistochemistry and in situ hybridization. The contribution of stem cells was directly evaluated in another group of animals that were by treated with granulocyte macrophage colony-stimulating factor (GM-CSF) early after implantation. We demonstrated the time-dependent generation of a fully differentiated tissue composed of fibroblasts, myofibroblasts, smooth muscle cells, endothelial cells and new blood vessels. Cells differentiated into early cardiomyocytes on membranes implanted in the left ventricles but not on those implanted in the aortas. Stem cell mobilization with GM-CSF led to more rapid tissue growth and differentiation. The GM-CSF effect on cell proliferation outlasted the treat ment period by several weeks. Circulating stem cells contributed to the development of a fully differentiated tissue on membranes placed within the left ventricle or descending aorta under physiological conditions. Early cardiomyocyte generation was identified only on membranes positioned within the left ventricle.


Asunto(s)
Diferenciación Celular , Factor Estimulante de Colonias de Granulocitos y Macrófagos/farmacología , Movilización de Célula Madre Hematopoyética , Células Madre Hematopoyéticas , Células Madre Pluripotentes , Disfunción Ventricular Izquierda/tratamiento farmacológico , Animales , Western Blotting , Fibroblastos/metabolismo , Técnicas para Inmunoenzimas , Miocitos Cardíacos/citología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos del Músculo Liso/metabolismo , ARN Mensajero/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Porcinos , Ingeniería de Tejidos
13.
Clin Res Cardiol ; 110(2): 194-199, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32671467

RESUMEN

BACKGROUND: Evidence is sparse and inconsistent on the role of a dual marker strategy (DMS) combining Copeptin with cardiac troponin T (cTnT) for instant rule-out of a non-ST-segment myocardial infarction (NSTEMI) when high sensitivity cardiac troponin T (hs-cTnT) is used. METHODS: Data on 10,329 patients from 5 trials were pooled to evaluate initial Copeptin in combination with hs-cTnT against a single marker strategy (SMS) based on hs-cTnT < limit of detection. Endpoints were sensitivities and negative predictive values (NPV) for rule-out of NSTEMI, 30-day all-cause mortality and rates of applicability for DMS or SMS. RESULTS: NPV for rule-out of NSTEMI was high, exceeding 99.0% for the lower limits of the 95% confidence intervals (99.0% vs 99.2%) for DMS and SMS, and NPV for all cause death at 30 days was similar with very low mortality after rule-out [0.07% (0.0-0.4%) vs 0.0% (0.0-1.2%), p = 1.0], but applicability was 2.4-fold higher [64.6% (63.0-66.2%) vs 27.9% (26.2%-29.7%), p < 0.001] with DMS than SMS. In a secondary analysis on DMS after inclusion of high risk patients, performance and applicability were similar. CONCLUSION: Findings corroborate the 2015 European Society of Cardiology recommendation to use dual marker strategy for instant rule-out of NSTEMI, extending evidence to hs-cTnT. Novel data demonstrate a comparably safe and effective instant rule-out with Copeptin in combination with hs-cTnT versus a single marker strategy based on very low hs-cTnT but a more than twofold higher applicability of the dual marker strategy without the need to exclude very early presenters or other important subgroups. Dual marker strategy using hs-cTnT at 99th percentile and Copeptin versus ESC 0-h immediate rule-out based on hs-cTnT < limit of detection.


Asunto(s)
Glicopéptidos/sangre , Infarto del Miocardio sin Elevación del ST/sangre , Troponina T/sangre , Anciano , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/diagnóstico , Pronóstico , Reproducibilidad de los Resultados
14.
J Mol Cell Cardiol ; 49(1): 142-51, 2010 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20363225

RESUMEN

We investigated the effect of pharmacological activation of the Ca(2+)-channel transient receptor potential cation channel, subfamily V, member 4 (TRPV4) on collateral growth in a pig hind limb-ischemia model thereby identifying subcellular mechanisms. Domestic pigs received femoral artery ligature and were randomly assigned to one of the following groups (each n=6): (1) 4alpha-phorbol 12,13-didecanoate (4alphaPDD) treatment; (2) treatment with an arterio-venous shunt (AV-shunt) distal to the occlusion; or (3) implantation of NaCl-filled minipump. Six sham-operated pigs acted as controls. Aortic and peripheral mean arterial pressure (MAP) measurements were performed to assess the collateral flow index (CFI). Tissue was isolated from M. quadriceps for immunohistochemistry and from isolated collateral arteries for quantitative real time PCR (qRT-PCR). Shortly after ligature the CFI dropped from 0.96+/-0.02 to 0.21+/-0.02 in all ligature-treated groups. In ligature-only-treated pigs CFI increased to 0.56+/-0.03 after 7days. Treatment with 4alphaPDD led to an enhancement of CFI compared with ligature alone (0.73+/-0.03). CD31-staining showed improved arteriolar density. Increased Ki67 staining in collaterals indicated proliferation. qRT-PCR and Western blot analysis showed upregulation or modulation of Ca(2+)-dependent transcription factors nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), Kv channel interacting protein 3, calsenilin (KCNIP3/CSEN/DREAM), and myocyte enhancer factor 2C (MEF2C) in 4alphaPDD- and AV-shunt-treated pigs compared with controls. Improved CFI after 4alphaPDD treatment identifies TRPV4 as an initial fluid shear-stress sensor and collateral remodelling and growth trigger. Subcellularly, modulation of Ca(2+)-dependent transcription factors indicates a pivotal role for Ca(2+)-signalling during arteriogenesis.


Asunto(s)
Miembro Posterior/irrigación sanguínea , Isquemia/fisiopatología , Animales , Aorta/metabolismo , Aorta/fisiopatología , Arterias/metabolismo , Arterias/fisiopatología , Vasos Sanguíneos/metabolismo , Vasos Sanguíneos/fisiopatología , Señalización del Calcio , Arteria Femoral/metabolismo , Arteria Femoral/fisiopatología , Arteria Femoral/cirugía , Miembro Posterior/metabolismo , Miembro Posterior/fisiopatología , Isquemia/metabolismo , Extremidad Inferior/irrigación sanguínea , Extremidad Inferior/fisiopatología , Masculino , Factores de Transcripción NFATC/metabolismo , Factores de Transcripción NFATC/farmacología , Forboles , Distribución Aleatoria , Estrés Mecánico , Sus scrofa/metabolismo
15.
Herz ; 35(4): 258-64, 2010 Jun.
Artículo en Alemán | MEDLINE | ID: mdl-22086477

RESUMEN

Tako-Tsubo cardiomyopathy (TTC), also referred to as stress cardiomyopathy (SCM), was first described in the 1990s and is characterized by transient left ventricular dysfunction. Its incidence represents 1-2% of all acute coronary syndromes (ACS). In most cases extreme emotional or physical stress precedes this syndrome. The majority of patients affected are postmenopausal women. Since its first description, various hypotheses regarding the pathophysiology of TTC have been discussed. From a historical perspective, coronary vasospasm has often been proposed as a possible cause of this disorder. However, reviews from numerous registries were able to demonstrate that coronary vasospasm plays only a minor role in the pathogenesis of TTC. Several groups showed disturbances in myocardial microcirculation and energy metabolism in the acute phase of TTC. Nevertheless, with regard to the data currently available, it cannot be differentiated whether these changes are the cause or rather the result of TTC. However, recent concepts include an excessive catecholamine overload and morphological changes which are unequivocally documented in TTC. The relation between elevated catecholamine levels and myocardial dysfunction analogous to TTC could be confirmed in animal experiments.In summary, it can be assumed that TTC is caused by an excessive cardiotoxic release of catecholamines. Ventricular dysfunction can be explained by increased numbers of ß-adrenergic receptors in the apex, leading to greater vulnerability to catecholamine overload. Individual anatomical differences in the sympathoadrenergic system and distribution from ß-adrenergic receptors are presumably responsible for the interindividual occurrence of wall motion abnormalities in TTC.


Asunto(s)
Catecolaminas/sangre , Ventrículos Cardíacos/fisiopatología , Modelos Cardiovasculares , Contracción Miocárdica , Receptores Adrenérgicos beta/metabolismo , Cardiomiopatía de Takotsubo/fisiopatología , Animales , Femenino , Humanos , Masculino
16.
J Int Med Res ; 36(4): 810-4, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18652778

RESUMEN

Rapamycin is an increasingly important immunosuppressive drug and reduces restenosis after coronary stenting, but its effects on cardiac contractility are largely unknown. We investigated the acute inotropic effects of rapamycin on isolated human cardiomyocytes. Cardiomyocytes were enzymatically isolated from right atrial appendages obtained during routine coronary artery bypass surgery. Cell morphology was examined by confocal microscopy. Cell contraction was recorded after electrical stimulation. Rapamycin elicited a concentration-dependent decrease in fractional cell shortening ranging from 14.3 +/- 2.6% at 10(-8) M rapamycin to 26.4 +/- 4.2% at 10(-5) M. Rapamycin also caused a concentration-dependent decrease in diastolic cell length. Contractile performance of isolated cardiomyocytes was well preserved, as evidenced by the profound positive inotropic effects of high extracellular calcium concentration and the beta-adrenoreceptor agonist isoproterenol. The acute negative inotropic effect of rapamycin on human cardiomyocytes might be due to altered calcium homeostasis through the binding of rapamycin to FKBP12.6 and its regulatory function on the ryanodine receptor, with increased calcium leakage from the sarcoplasmic reticulum.


Asunto(s)
Inmunosupresores/farmacología , Contracción Miocárdica/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Sirolimus/farmacología , Calcio/metabolismo , Forma de la Célula , Células Cultivadas , Relación Dosis-Respuesta a Droga , Humanos , Contracción Miocárdica/fisiología , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo
17.
J Int Med Res ; 36(5): 986-91, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18831892

RESUMEN

2-Deoxy-D-glucose (2-DG) is a glucose analogue that has been proposed for cancer therapy due to its cytostatic properties. Its effect on the proliferation of smooth muscle cells and endothelial cells has not been fully clarified. The aims of this study were to investigate the effects of 2-DG on the proliferation of porcine aortic endothelial cells (PAEC) and porcine smooth muscle cells (PSMC), to establish an overview of its dose-dependent inhibitory capacity and to examine whether the short-term incubation of cells with 2-DG has an impact on cell proliferation in culture. Our results showed a dose-dependent significant inhibitory effect on proliferation, which was more pronounced in PSMC than in PAEC. Even after short-term incubation of cells with 2-DG, relevant inhibition of proliferation was documented. The clinical application of 2-DG might be a promising concept by inhibiting cells that show a potentially rapid proliferation in response to non-malignant stimuli, such as smooth muscle cells after intracoronary stenting.


Asunto(s)
Antimetabolitos/farmacología , Proliferación Celular/efectos de los fármacos , Desoxiglucosa/farmacología , Células Endoteliales , Músculo Liso Vascular/citología , Miocitos del Músculo Liso , Animales , Aorta/citología , Relación Dosis-Respuesta a Droga , Células Endoteliales/efectos de los fármacos , Células Endoteliales/fisiología , Miocitos del Músculo Liso/efectos de los fármacos , Miocitos del Músculo Liso/fisiología , Porcinos
18.
Clin Res Cardiol ; 107(11): 1033-1039, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29752526

RESUMEN

BACKGROUND: The presence of left bundle branch block (LBBB) represents a particular challenge in properly measuring the QT interval. Here we demonstrate the applicability of the "Bogossian formula" in pacemaker patients with LBBB due to apical or nonapical right ventricular (RV) pacing and preserved left ventricular function. METHODS: A total of 163 patients with a cardiac one- or two-chamber pacemaker were included in this prospective, multicentre observational study. Twelve-lead ECG recordings were obtained during both intrinsic rhythm and RV pacing with induced LBBB. The QT interval measured during LBBB was corrected using the Bogossian formula to obtain the "modified QT" (QTm). The QTmc interval was calculated with the Bazett formula, and this was compared with the QTc interval during intrinsic rhythm. RESULTS: Eighty-three patients (78 ± 9 years; male n = 83) with apical and eighty patients (71 ± 13 years; male n = 80) with non-apical RV pacing were included in this study. In the apical group the QTmc was determined to be 444 ± 39 ms in paced rhythm and the QTc interval 413 ± 36 ms in intrinsic rhythm. In the non-apical group these values were 430 ± 34 ms in paced and 416 ± 32 ms in intrinsic rhythm. CONCLUSION: The Bogossian formula is a reliable tool for QTc interval evaluation in pacemaker patients with LBBB due to apical or non-apical RV pacing. However, an overestimation of 30 ms should be included in the calculation.


Asunto(s)
Bloqueo de Rama/diagnóstico , Estimulación Cardíaca Artificial/métodos , Diagnóstico por Computador/métodos , Electrocardiografía , Ventrículos Cardíacos/fisiopatología , Función Ventricular Izquierda/fisiología , Anciano , Bloqueo de Rama/fisiopatología , Bloqueo de Rama/terapia , Femenino , Estudios de Seguimiento , Humanos , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados
19.
Int J Cardiol ; 265: 40-46, 2018 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-29885699

RESUMEN

BACKGROUND: N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) levels correlate with higher peri-procedural mortality after transcatheter aortic valve replacement (TAVR). The long-term prognostic value of NT-proBNP within the first days after TAVR, however, remains unclear. This study examined early changes in NT-proBNP prior to and within 6 days after TAVR, the diagnostic value of this biomarker regarding aortic regurgitation (AR), and its prognostic value regarding one-year mortality. METHODS AND RESULTS: NT-proBNP concentrations were measured in 504 consecutive patients undergoing transapical (TA) or transfemoral (TF) TAVR before and directly after TAVR as well as 4 h and 1, 2, 3, and 6 days after TAVR. The follow-up period was 1 year. NT-proBNP was elevated in all patients at baseline (median 2141 ng/L [IQR 1021-5319 ng/L]). NT-proBNP changes in the first 6 days after TAVR showed significant differences depending on the approach, with a greater and more prolonged rise evident in TA-TAVR patients. NT-proBNP was an independent predictor of mortality in TA patients with AR, with an AUC of 0.794 (95% CI 0.663-0.925; P = 0.003) when measured on day 3 after TAVR. For TF patients with AR and reduced left ventricular systolic function, the AUC for prediction of mortality was 0.897 (95% CI 0.778-1.0; P = 0.004) on day 2. CONCLUSIONS: The prognostic information of early post-procedural NT-proBNP concentrations is superior to pre-procedural values regarding all-cause mortality within 1 year. Post-procedural NT-proBNP must be interpreted in relation to the TAVR approach. NT-proBNP predicts mortality in TF-TAVR patients with AR and reduced left ventricular function.


Asunto(s)
Insuficiencia de la Válvula Aórtica/sangre , Insuficiencia de la Válvula Aórtica/mortalidad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Disfunción Ventricular Izquierda/sangre , Disfunción Ventricular Izquierda/mortalidad , Anciano , Anciano de 80 o más Años , Insuficiencia de la Válvula Aórtica/cirugía , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Mortalidad/tendencias , Estudios Prospectivos , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/tendencias , Disfunción Ventricular Izquierda/cirugía
20.
J Interv Card Electrophysiol ; 47(1): 75-82, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27033358

RESUMEN

PURPOSE: Lesion formation is a critical determinant of technical and clinical success of pulmonary vein isolation. Different catheter designs aim to enhance tissue contact during ablation to enable optimized lesion formation. We analyzed procedural characteristics and predictors of clinical success in patients ablated with three different contemporary ablation catheters. METHODS: Two hundred sixty-eight sequentially included patients receiving pulmonary vein isolation (PVI) with conventional (n = 122), contact-force (n = 96) and flexible-tip (n = 60) catheters were followed for a median of 14.1 months with 7d-Holter-monitoring and TTE at 3, 6, 12, and 24 months. Baseline characteristics and follow-up times were homogeneous across all groups. RESULTS: Multivariable Cox proportional hazard regression for arrhythmia recurrence demonstrated a favorable hazard ratio for contact-force and flexible-tip catheters vs. conventional open irrigation catheters. Procedure time and fluoroscopy time were shorter for contact-force and flexible-tip catheters versus conventional catheters, but equal between. Linear lesions were applied in 58 % of contact-force and 66 % of flexible-tip cases, and CFAEs were targeted in 26 % of either. CONCLUSIONS: Our non-randomized prospectively collected data do not show a difference in observed procedure characteristics and in clinical outcome for flexible-tip versus contact-force catheter designs, while both display improved performance against conventional open irrigated-tip catheters. Linear lesions and CFAEs ablation were not associated with improved arrhythmia-free survival.


Asunto(s)
Fibrilación Atrial/epidemiología , Fibrilación Atrial/cirugía , Ablación por Catéter/instrumentación , Ablación por Catéter/estadística & datos numéricos , Monitoreo Intraoperatorio/instrumentación , Monitoreo Intraoperatorio/estadística & datos numéricos , Anciano , Fibrilación Atrial/diagnóstico , Ablación por Catéter/métodos , Supervivencia sin Enfermedad , Módulo de Elasticidad , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Prevalencia , Recurrencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estrés Mecánico , Resultado del Tratamiento
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