RESUMEN
BACKGROUND: Despite excellent data on lowering long-term stroke and all-cause mortality rates, currently, only 25-40% of atrial fibrillation (AF) patients undergo simultaneous surgical ablation therapy (SA) during cardiac surgery. Surgeon's fear exposing their patients to an additional, unjustified, and disproportionate risk when performing SA in AF patients presenting with sinus rhythm (SR) before surgery. To clarify the influence of preoperative SR before SA for AF, we conducted a subgroup analysis of the German Cardiosurgical Atrial Fibrillation (CASE-AF) register. METHODS: Between September 2016 and August 2020, 964 AF patients with an underlying cardiac disease were scheduled for surgery with SA and enrolled in the CASE-AF register. Data prospectively were collected and analyzed retrospectively. We divided the entire cohort into an SR-group (38.2%, N = 368) and an AF-group (61.8%, N = 596), based on preoperative heart rhythm. RESULTS: Over half of the patients were moderately affected by their AF, with no difference between the groups (European Heart Rhythm Association class ≥IIb: SR-group 54.2% versus AF-group 58.5%, P = .238). The AF-group had a higher preoperative EuroSCORE II (4.8 ± 8.0% versus 4.2 ± 6.3%, P = .014). In-hospital mortality (SR-group 0.8% versus AF-group 1.7%, P = .261), major perioperative adverse cardiac and cerebrovascular events (SR-group 2.7% versus AF-group 3.5%, P = .500), and the new pacemaker implantation rate (SR-group 6.0% versus AF-group 5.9%, P = .939) were low and showed and no group difference. Logistic regression analysis showed a protective effect for preoperative SR to perioperative complications in AF patients undergoing SA (odds ratio (OR) 0.72 (95% CI 0.52 - 0.998); P = .0485). CONCLUSIONS: Concomitant SA in AF patients presenting in SR before cardiac surgery is safe, has a low perioperative risk profile, and should be carried out with almost no exceptions.
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Fibrilación Atrial/cirugía , Ablación por Catéter/métodos , Sistema de Conducción Cardíaco/fisiopatología , Frecuencia Cardíaca/fisiología , Complicaciones Posoperatorias/epidemiología , Anciano , Fibrilación Atrial/fisiopatología , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Periodo Preoperatorio , Estudios ProspectivosRESUMEN
Mesenchymal stem cells (MSC) have been used to treat different clinical conditions although the mechanisms by which pathogenetic processes are affected are still poorly understood. We have previously analyzed the homing of bone marrow-derived MSC to diseased tissues characterized by a high degree of mononuclear cell infiltration and postulated that MSC might modulate inflammatory responses. Here, we demonstrate that MSC mitigate adverse tissue remodeling, improve organ function, and extend lifespan in a mouse model of inflammatory dilative cardiomyopathy (DCM). Furthermore, MSC attenuate Lipopolysaccharide-induced acute lung injury indicating a general role in the suppression of inflammatory processes. We found that MSC released sTNF-RI, which suppressed activation of the NFκBp65 pathway in cardiomyocytes during DCM in vivo. Substitution of MSC by recombinant soluble TNF-R partially recapitulated the beneficial effects of MSC while knockdown of TNF-R prevented MSC-mediated suppression of the NFκBp65 pathway and improvement of tissue pathology. We conclude that sTNF-RI is a major part of the paracrine machinery by which MSC effect local inflammatory reactions.
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Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Dilatada/patología , Trasplante de Células Madre Mesenquimatosas/métodos , Factor de Necrosis Tumoral alfa/metabolismo , Animales , Western Blotting , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente , Técnicas de Silenciamiento del Gen , Corazón , Inflamación/inmunología , Inflamación/patología , Pulmón/inmunología , Pulmón/patología , Espectrometría de Masas , Ratones , Ratones Transgénicos , Transducción de Señal/inmunología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
AIMS: Initial studies of catheter-based renal arterial sympathetic denervation to lower blood pressure in resistant hypertensive patients renewed interest in the sympathetic nervous system's role in the pathogenesis of hypertension. However, the SYMPLICITY HTN-3 study failed to meet its prespecified blood pressure lowering efficacy endpoint. To date, only a limited number of studies have described the microanatomy of renal nerves, of which, only two involve humans. METHODS AND RESULTS: Renal arteries were harvested from 15 cadavers from the Klinikum Osnabruck and Schuchtermann Klinik, Bad Rothenfelde. Each artery was divided longitudinally in equal thirds (proximal, middle, and distal), with each section then divided into equal superior, inferior, anterior, and posterior quadrants, which were then stained. Segments containing no renal nerves were given a score value = 0, 1-2 nerves with diameter <300 µm a score = 1; 3-4 nerves or nerve diameter 300-599 µm a score = 2, and >4 nerves or nerve diameter ≥600 µm a score = 3. A total of 22 renal arteries (9 right-sided, 13 left-sided) were suitable for examination. Overall, 691 sections of 5 mm thickness were prepared. Right renal arteries had significantly higher mean innervation grade (1.56 ± 0.85) compared to left renal arteries (1.09 ± 0.87) (P < 0.001). Medial (1.30 ± 0.59) and distal (1.39 ± 0.62) innervation was higher than the proximal (1.17 ± 0.55) segments (p < 0.001). When divided in quadrants, the anterior (1.52 ± 0.96) and superior (1.71 ± 0.89) segments were more innervated compared to posterior (0.96 ± 0.72) and inferior (0.90 ± 0.68) segments (P < 0.001). CONCLUSIONS: That the right renal artery has significantly higher innervation scores than the left. The anterior and superior quadrants of the renal arteries scored higher in innervation than the posterior and inferior quadrants did. The distal third of the renal arteries are more innervated than the more proximal segments. These findings warrant further evaluation of the spatial innervation patterns of the renal artery in order to understand how it may enhance catheter-based renal arterial denervation procedural strategy and outcomes. CONDENSED ABSTRACT: The SYMPLICITY HTN-3 study dealt a blow to the idea of the catheter-based renal arterial sympathetic denervation. We investigated the location and patterns of periarterial renal nerves in cadaveric human renal arteries. To quantify the density of the renal nerves we created a novel innervation score. On average the right renal arteries were significantly more densely innervated than the left renal arteries, the anterior and superior segments were significantly more innervated compared to the posterior and inferior segments, absolute innervation scores in the proximal third of the left or right renal arteries were always lower when compared to distal segments. These findings may enhance catheter-based renal arterial denervation procedural strategy and outcomes.
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Hipertensión/cirugía , Arteria Renal , Simpatectomía , Sistema Nervioso Simpático/cirugía , Anciano , Presión Sanguínea/fisiología , Cadáver , Femenino , Humanos , Riñón/irrigación sanguínea , Masculino , Persona de Mediana Edad , Modelos Anatómicos , Arteria Renal/inervación , Arteria Renal/patología , Simpatectomía/efectos adversos , Simpatectomía/métodosRESUMEN
Cardiomyocytes continuously generate the contractile force to circulate blood through the body. Imbalances in contractile performance or energy supply cause adaptive responses of the heart resulting in adverse rearrangement of regular structures, which in turn might lead to heart failure. At the cellular level, cardiomyocyte remodeling includes (1) restructuring of the contractile apparatus; (2) rearrangement of the cytoskeleton; and (3) changes in energy metabolism. Dedifferentiation represents a key feature of cardiomyocyte remodeling. It is characterized by reciprocal changes in the expression pattern of "mature" and "immature" cardiomyocyte-specific genes. Dedifferentiation may enable cardiomyocytes to cope with hypoxic stress by disassembly of the energy demanding contractile machinery and by reduction of the cellular energy demand. Dedifferentiation during myocardial repair might provide cardiomyocytes with additional plasticity, enabling survival under hypoxic conditions and increasing the propensity to enter the cell cycle. Although dedifferentiation of cardiomyocytes has been described during tissue regeneration in zebrafish and newts, little is known about corresponding mechanisms and regulatory circuits in mammals. The recent finding that the cytokine oncostatin M (OSM) is pivotal for cardiomyocyte dedifferentiation and exerts strong protective effects during myocardial infarction highlights the role of cytokines as potent stimulators of cardiac remodeling. Here, we summarize the current knowledge about transient dedifferentiation of cardiomyocytes in the context of myocardial remodeling, and propose a model for the role of OSM in this process.
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Corazón/fisiología , Miocitos Cardíacos/citología , Animales , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Desdiferenciación Celular , Humanos , Miocitos Cardíacos/metabolismo , Oncostatina M/metabolismo , Receptores de Oncostatina M/antagonistas & inhibidores , Receptores de Oncostatina M/genética , Receptores de Oncostatina M/metabolismo , Regeneración , Remodelación VentricularRESUMEN
BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a recognized therapeutic option for high-risk and inoperable patients with aortic valve stenosis. The choice of access route is a matter of debate. We are presenting our 5-year experience of transapical TAVI dominance. PATIENTS: This single-center study includes 575 patients. Two groups were compared: transapical (TA) and transfemoral (TF) with 454 and 121 patients, respectively. Individual access route decision was made by our heart team following a clinical and computed tomography (CT) data based nonbiased strategy. The same team performed all procedures. The mean logistic EuroSCORE was significantly higher in the TA group, however, without difference in STS score. The number of patients with coronary artery disease, previous cardiac surgery, and low left ventricular ejection fraction was higher in the TA group. There were no significant differences in age and presence of other comorbidities. RESULTS: Procedural success in both TA and TF groups was high (97.9% and 97.6%). No patient died during the procedure. Patient survival (30 days: TF, 97.5% vs. TA, 95.7%; 1 year: TF, 94.6% vs. TA, 81.8%; 2 years: TF, 84.7% vs. TA, 76.7%; 3 years: TF, 59.9% vs. TA, 67.8%) and a low TF vascular complication rate (1.6%) are encouraging compared with other registry data. CONCLUSION: A "no competition" team approach strategy along with an experienced hybrid team leads to fewer vascular complications and better outcomes for both TA and TF TAVI patients.
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Estenosis de la Válvula Aórtica/cirugía , Cateterismo Cardíaco/métodos , Complicaciones Posoperatorias/epidemiología , Guías de Práctica Clínica como Asunto , Medición de Riesgo/métodos , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Anciano de 80 o más Años , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Cateterismo Cardíaco/normas , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Ingle , Humanos , Incidencia , Masculino , Complicaciones Posoperatorias/prevención & control , Radiografía , Sistema de Registros , Estudios Retrospectivos , Reemplazo de la Válvula Aórtica Transcatéter/normas , Resultado del TratamientoRESUMEN
Heart failure (HF) is a common and potentially deadly condition, which frequently develops as a consequence of various diseases of the heart. The incidence of heart failure continuously increases in aging societies illustrating the need for new therapeutic approaches. We recently discovered that continuous activation of oncostatin M (OSM), a cytokine of the interleukin-6 family that induces dedifferentiation of cardiomyocytes, promotes progression of heart failure in dilative cardiomyopathy. To evaluate whether inhibition of OSM signaling represents a meaningful therapeutic approach to prevent heart failure we attenuated OSM-receptor (Oß) signaling in a mouse model of inflammatory dilative cardiomyopathy. We found that administration of an antibody directed against the extracellular domain of Oß or genetic inactivation of a single allele of the Oß gene reduced cardiomyocyte remodeling and dedifferentiation resulting in improved cardiac performance and increased survival. We conclude that pharmacological attenuation of long-lasting Oß signaling is a promising strategy to treat different types and stages of HF that go along with infiltration by OSM-releasing inflammatory cells.
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Anticuerpos Neutralizantes/farmacología , Cardiomiopatía Dilatada/metabolismo , Subunidad beta del Receptor de Oncostatina M/antagonistas & inhibidores , Transducción de Señal/fisiología , Animales , Western Blotting , Desdiferenciación Celular , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/metabolismo , Humanos , Inflamación/metabolismo , Factor I del Crecimiento Similar a la Insulina , Imagen por Resonancia Magnética , Ratones , Ratones Noqueados , Ratones Transgénicos , Microscopía Fluorescente , Miocitos Cardíacos/citología , Miocitos Cardíacos/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
OBJECTIVE: Collateral artery growth or arteriogenesis is the primary means of the circulatory system to maintain blood flow in the face of major arterial occlusions. Arteriogenesis depends on activation of fibroblast growth factor (FGF) receptors, but relatively little is known about downstream mediators of FGF signaling. METHODS AND RESULTS: We screened for signaling components that are activated in response to administration of FGF-2 to cultured vascular smooth muscle cells (VSMCs) and detected a significant increase of Rap2 but not of other Ras family members, which corresponded to a strong upregulation of Rap2 and C-Raf in growing collaterals from rabbits with femoral artery occlusion. Small interfering RNAs directed against Rap2 did not affect FGF-2 induced proliferation of VSMC but strongly inhibited their migration. Inhibition of FGF receptor-1 (FGFR1) signaling by infusion of a sulfonic acid polymer or infection with a dominant-negative FGFR1 adenovirus inhibited Rap2 upregulation and collateral vessel growth. Similarly, expression of dominant-negative Rap2 blocked arteriogenesis, whereas constitutive active Rap2 enhanced collateral vessel growth. CONCLUSIONS: Rap2 is part of the arteriogenic program and acts downstream of the FGFR1 to stimulate VSMC migration. Specific modulation of Rap2 might be an attractive target to manipulate VSMC migration, which plays a role in numerous pathological processes.
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Arteriopatías Oclusivas/metabolismo , Movimiento Celular , Músculo Liso Vascular/metabolismo , Miocitos del Músculo Liso/metabolismo , Neovascularización Fisiológica , Proteínas de Unión al GTP rap/metabolismo , Animales , Arteriopatías Oclusivas/genética , Arteriopatías Oclusivas/patología , Arteriopatías Oclusivas/fisiopatología , Proliferación Celular , Circulación Colateral , Modelos Animales de Enfermedad , Arteria Femoral/metabolismo , Arteria Femoral/patología , Arteria Femoral/fisiopatología , Arteria Femoral/cirugía , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Células HEK293 , Humanos , Ligadura , Ratones , Músculo Liso Vascular/patología , Miocitos del Músculo Liso/patología , Interferencia de ARN , Conejos , Receptor Tipo 1 de Factor de Crecimiento de Fibroblastos/metabolismo , Flujo Sanguíneo Regional , Factores de Tiempo , Transfección , Proteínas de Unión al GTP rap/genéticaRESUMEN
Background: A logistic European System for Cardiac Operative Risk Evaluation (logEuroSCORE) ≥20% is frequently recognised as a finite criteria for transcatheter aortic valve implantation (TAVI) reimbursement, despite guideline modifications to reflect the appropriacy of TAVI in selected lower-risk patients. The aim was to evaluate the clinical value of this threshold cut-off in TAVI patients and to identify factors associated with mortality in those below this threshold. Methods: We analysed data from a single-centre, German, observational, TAVI-patient registry, gathered between 2008 and 2016. Patients were stratified by logEuroSCORE (≥ or <20%) for comparisons. Logistic regression was performed to identify predictors of mortality at 1 year, with this analysis used to generate a calculated ('real') risk value for each patient. Results: 1679 patients (logEuroSCORE <20%: n=789; logEuroSCORE ≥20%: n=890) were included. LogEuroSCORE <20% patients were significantly younger (80.1 vs 81.6 years; p<0.001) and less comorbid than logEuroSCORE ≥20% patients, with a higher rate of transfemoral TAVI (35.6% vs 26.1%; p<0.001) and predilation (70.0% vs 63.3%; p=0.004). Patients with a logEuroSCORE <20% experienced more vascular complications (3.4% vs 1.5%; p=0.010). One-year survival was 88.3% in the logEuroSCORE <20% and 81.8% in the logEuroSCORE ≥20% group (p=0.005), with the calculated mortality risk falling within 2% of the logEuroSCORE in just 12.9% of patients. In the logEuroSCORE <20% group, only coronary artery disease was significantly predictive of 1-year mortality (OR 2.408; 95% CI 1.361 to 4.262; p=0.003). Conclusions: At our institution, patients with a logEuroSCORE <20% selected for TAVI have excellent outcomes. The decision not to reimburse TAVI in such patients may be viewed as inappropriate.
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Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Toma de Decisiones Clínicas , Técnicas de Apoyo para la Decisión , Determinación de la Elegibilidad , Selección de Paciente , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/mortalidad , Estenosis de la Válvula Aórtica/fisiopatología , Determinación de la Elegibilidad/economía , Planes de Aranceles por Servicios , Femenino , Alemania , Humanos , Masculino , Valor Predictivo de las Pruebas , Sistema de Registros , Medición de Riesgo , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de Tiempo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Reemplazo de la Válvula Aórtica Transcatéter/economía , Reemplazo de la Válvula Aórtica Transcatéter/mortalidad , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to validate myocardial microdialysis measurements in patients after myocardial infarction with or without associated postoperative functional recovery in order to develop a highly sensitive tool for real-time in vivo detection of microcellular disorder during cardiac operations. METHODS: In 20 patients undergoing coronary artery bypass grafting, microdialysis catheters were implanted into scar or hibernating segments detected by means of magnetic resonance imaging, and into a vital area of the right ventricle (control). Myocardial glucose, lactate and pyruvate were analyzed perioperatively. Myocardial ethanol washout was measured as a sign of recovered local blood flow. RESULTS: After surgical revascularization, improvement of wall motion was found in all hibernating segments compared to the scar segments paralleling an increased glucose delivery to the tissue and increased myocardial tissue flow. The myocardial glucose/lactate ratio and pyruvate also showed significantly higher values. Microdialytic measurements of the viable segments were comparable with those of the right ventricle. CONCLUSIONS: Our results indicate that microdialysis measurements parallel magnetic resonance imaging findings in patients with revascularization of chronic ischemic myocardium with dyskinetic segments. The metabolism of those segments is characterized by a significantly increased tissue flow, an increased utilization of glucose and a better oxidative nutrition.
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Puente de Arteria Coronaria , Isquemia Miocárdica/metabolismo , Miocardio/metabolismo , Circulación Coronaria , Etanol , Glucosa/metabolismo , Humanos , Ácido Láctico/metabolismo , Imagen por Resonancia Magnética , Microdiálisis , Contracción Miocárdica , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/cirugía , Ácido Pirúvico/metabolismo , Recuperación de la Función , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
OBJECTIVES: It may be expected that patients with left ventricular dysfunction may be at greater risk of complications after transcatheter aortic valve implantation (TAVI) via transapical (TA) access compared with via transfemoral (TF) access. There is a lack of data comparing the outcomes of TAVI using TA and TF access in patients with a reduced left ventricular ejection fraction (EF). METHODS: This is a retrospective analysis of data from a high-volume heart centre in Germany. TAVI access route assignment was based on a 'best for TF' approach, where only patients who met a strict set of criteria underwent TF-TAVI, with the remainder receiving TA-TAVI. For this analysis, patients were included if they had a pre-TAVI EF of ≤ 40%. Early mortality and late (1-year) mortality were compared through multivariate logistic regression. RESULTS: A total of 342 patients in the registry had an EF of ≤ 40%, of which 74.9% underwent TA-TAVI and 25.1% underwent TF-TAVI. Higher proportions of the TA group presented with certain comorbidities, and their logistic EuroSCORE and Society of Thoracic Surgeons (STS) risk scores were higher than in the TF group. At 1 year, TA access was associated with greater mortality in the univariate analysis (odd ratio 2.43; 95% confidence interval 1.04-5.69). However, after multivariate adjustment, no significant differences were found in either 30-day or 1-year mortality rates. CONCLUSIONS: The data suggest that, for patients with a reduced EF, TA-TAVI is not associated with a poorer outcome compared with TF-TAVI. Therefore, TA access should not be discounted based on the presence of left ventricular dysfunction alone.
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Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Sistema de Registros , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/fisiopatología , Ecocardiografía , Femenino , Prótesis Valvulares Cardíacas , Humanos , Masculino , Oportunidad Relativa , Estudios Retrospectivos , Volumen SistólicoRESUMEN
Aims: Myocardial infarction (MI) causes a massive increase of macrophages in the heart, which serve various non-redundant functions for cardiac repair. The identities of signals controlling recruitment of functionally distinct cardiac macrophages to sites of injury are only partially known. Previous work identified Regenerating islet-derived protein 3 beta (Reg3ß) as a novel factor directing macrophages to sites of myocardial injury. Herein, we aim to characterize functionally distinct macrophage subsets and understand the impact of different members of the Reg protein family including Reg3ß, Reg3γ, and Reg4 on their accumulation in the infarcted heart. Methods and results: We have determined dynamic changes of three phenotypically distinct tissue macrophage subpopulations in the mouse heart after MI by flow cytometry. RNA sequencing and bioinformatics analysis identified inflammatory gene expression patterns in MHC-IIhi/Ly6Clo and MHC-IIlo/Ly6Clo cardiac tissue macrophages while Ly6Chi cardiac tissue macrophages are characterized by gene activities associated with healing and revascularization of damaged tissue. Loss- and gain-of-function experiments revealed specific roles of Reg proteins for recruitment of cardiac tissue macrophage subpopulations to the site of myocardial injury. We found that expression of Reg3ß, Reg3γ, and Reg4 is strongly increased after MI in mouse and human hearts with Reg3ß providing the lead, followed by Reg3γ and Reg4. Inactivation of the Reg3ß gene prevented the increase of all types of cardiac tissue macrophages shortly after MI whereas local delivery of Reg3ß, Reg3γ, and Reg4 selectively stimulated recruitment of MHC-IIhi/Ly6Clo and MHC-IIlo/Ly6Clo but repressed accumulation of Ly6Chi cardiac tissue macrophages. Conclusion: We conclude that distinct cardiac macrophage subpopulations are characterized by substantially different gene expression patterns reflecting their pathophysiological role after MI. We argue that sequential, local production of Reg proteins orchestrates accumulation of macrophage subsets, which seem to act in a parallel or partially overlapping rather than in a successive manner.
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Quimiotaxis , Macrófagos/metabolismo , Infarto del Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Asociadas a Pancreatitis/metabolismo , Animales , Antígenos Ly/metabolismo , Línea Celular , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Antígenos de Histocompatibilidad Clase II/metabolismo , Humanos , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Miocitos Cardíacos/patología , Proteínas de Neoplasias/genética , Subunidad beta del Receptor de Oncostatina M/genética , Subunidad beta del Receptor de Oncostatina M/metabolismo , Proteínas Asociadas a Pancreatitis/deficiencia , Proteínas Asociadas a Pancreatitis/genética , Fenotipo , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
BACKGROUND: Regenerating islet-derived protein 3 beta (Reg3ß) is a cardiomyocyte-derived chemokine for macrophages that is upregulated after myocardial infarction (MI) in mice. Here, we hypothesized that monitoring Reg3ß expression might provide specific information on the degree of cardiac inflammation, which is a key determinant in disease progression and prognosis of patients with acute coronary syndrome (ACS). METHODS AND RESULTS: The expression of Reg3ß and other inflammatory markers including C-reactive protein (CRP) and myeloperoxidase (MPO) was measured by immunoblotting at serial time points in the hearts and serum of mice with acute MI. We identified a rapid increase of Reg3ß, CRP and MPO expression in cardiac tissue and serum within the first 24â¯h after MI. The expression of Reg3ß peaked at day 4 and thereby paralleled the kinetic profile of the early immune-inflammatory response at sites of cardiac injury, which has been characterized by multicolor flow cytometry. In a retrospective analysis including 322 ACS patients and 117 apparently healthy individuals, we detected increased Reg3ß serum concentrations in ACS patients on admission by ELISA. Multiple regression analysis revealed significant relationships between Reg3ß and hs-CRP, age, diabetes and NT-proBNP in ACS. Moreover, elevated Reg3ß levels on admission were associated with an increased risk of death independent of cardiovascular risk factors and hs-CRP. CONCLUSIONS: Reg3ß is a prognostic biomarker for ACS and is strongly associated with the intensity of cardiac inflammation. Accordingly, Reg3ß may complement established strategies of acute risk assessment in the management of ACS.
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Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/fisiopatología , Proteínas Asociadas a Pancreatitis/sangre , Síndrome Coronario Agudo/diagnóstico , Adulto , Animales , Biomarcadores/sangre , Estudios de Cohortes , Electrocardiografía/tendencias , Femenino , Estudios de Seguimiento , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , PronósticoRESUMEN
Subcoronary implantation of the Medtronic stentless bioprosthesis and an extension using a vascular tube prosthesis provide a safer alternative to the more invasive conventional composite graft replacement or a full root replacement using a homograft or a stentless valve. The advantage lies in eliminating the need for coronary mobilisation and anastomosis which actually lead to the increased risk in those procedures.
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Válvula Aórtica/cirugía , Bioprótesis , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Anciano , Anciano de 80 o más Años , Enfermedades de la Aorta/complicaciones , Enfermedades de la Aorta/cirugía , Enfermedades de las Válvulas Cardíacas/complicaciones , Prótesis Valvulares Cardíacas , Humanos , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVE: Mutations in the genes encoding fibrillin-1 (FBN1) and transforming growth factor beta receptor type II (TGFBR2) are known causes of Marfan syndrome (MFS) and related disorders. However, a sound correlation between the genotype and the cardiovascular phenotype has not yet been established. The objective of the present study was to identify novel mutations in FBN1 and TGFBR2 and to assess whether the type of mutation is linked to a particular clinical subtype of the cardiovascular condition. METHODS: The clinical records of 36 patients referred to us for molecular genetic diagnosis were reviewed to assess the course and severity of the vascular deterioration. A semiautomatic protocol was established enabling a rapid and cost-effective screening of the genes FBN1 and TGFBR2 by direct sequencing of all coding exons and flanking intronic regions. RESULTS: Novel mutations in FBN1 and TGFBR2 were detected in 12 and 2 patients, respectively. Four individuals carried a recurrent mutation in FBN1. Throughout the study cohort, the incidence of aortic dissections per se did not depend on the type of mutation. However, we found that mutations affecting the calcium-binding epidermal growth factor-like domain were more frequently associated with a dissection of distal parts of the aorta than mutations that lead to a premature termination codon (chi(1)(2): p=0.013), suggesting that the spatio-temporal pattern of vascular deterioration may vary with the type of mutation. CONCLUSIONS: Detecting a mutation in the genes FBN1 and TGFBR2 proves the genetic origin of vascular findings and allows the identification of family members at risk who should undergo preventive checkups. Routine genetic testing of patients with suspected MFS or thoracic aortic aneurysms/dissections could provide further insight into genotype/phenotype correlations related to aortic dissection.
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Aneurisma de la Aorta/genética , Disección Aórtica/genética , Adolescente , Adulto , Disección Aórtica/cirugía , Aorta/cirugía , Aneurisma de la Aorta/cirugía , Proteínas de Unión al Calcio/genética , Estudios de Cohortes , Factor de Crecimiento Epidérmico/genética , Femenino , Fibrilina-1 , Fibrilinas , Genotipo , Válvulas Cardíacas/cirugía , Humanos , Masculino , Síndrome de Marfan/complicaciones , Síndrome de Marfan/genética , Síndrome de Marfan/cirugía , Proteínas de Microfilamentos/genética , Persona de Mediana Edad , Mutación , Fenotipo , Proyectos Piloto , Proteínas Serina-Treonina Quinasas , Receptor Tipo II de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/genéticaRESUMEN
INTRODUCTION: The "transfemoral (TF) first" approach to access route selection in transcatheter aortic valve implantation (TAVI) is popular; however, the risk of major vascular complications is substantial. The "best for TF" approach identifies only the patients with ideal anatomy for TF-TAVI, potentially minimizing complications. AIM: To characterize the outcomes of patients undergoing TAVI at a large-volume site that employs this approach. MATERIAL AND METHODS: Patients who underwent TAVI at the Bad Rothenfelde Heart Centre between 2008 and 2016 were consecutively enrolled. Findings were compared to those from large, multicenter registries. RESULTS: Of the 1,644 patients enrolled, 1,140 underwent TA- and 504 TF-TAVI. Comorbidities were more frequent in TA patients, who also had higher risk scores (EuroSCORE: 25.5% vs. 21.2%; STS score: 11.0% vs. 7.5%; p < 0.001 for both). Rates of conversion to open surgery, major vascular complications and intra-procedural mortality did not differ between groups. At 30 days, mortality rates were higher in the TA group (3.9% vs. 1.9%, p = 0.036). Stroke/transient ischemic attack and permanent pacemaker implantation rates did not differ significantly between groups (2.0% and 9.1% overall, respectively). Compared to multicenter registries, trends in mortality and complication rates were similar, though magnitudes were lower in the present study. In contrast with the present study, major vascular complication rates in multicenter registries are significantly higher for TF compared to TA patients. CONCLUSIONS: At this high-volume center, the use of a "best for TF" approach to TAVI resulted in low mortality and complication rates.
RESUMEN
BACKGROUND: For the first time, microdialysis was used to investigate in vivo and online the myocardial metabolism during and after cardiac surgery in patients treated with two different methods of myocardial protection. METHODS: Thirty patients underwent standard CABG with one of two different methods of myocardial protection. The patients were randomised to receive either cold blood (COLD group) or warm modified Calafiore cardioplegia (WARM group). Microdialysis probes were implanted into the myocardium of left ventricular apical region of the heart. Cardioplegia was given antegrade only. Microdialysis measurements were performed at time intervals before, during and 24 h after cardiopulmonary bypass and analysed for glucose, lactate, pyruvate and glycerol. RESULTS: Myocardial lactate concentrations were significantly higher in the WARM group compared with that of the COLD group, while serum lactate was comparable. Glycerol was significantly higher at the end of the clamping time in the WARM group. At the same time the glucose-lactate ratio as a marker of nutritional disorder had significantly lower levels in the WARM group. The cumulative CK-MB release over 24 h was significantly higher in those hearts protected with warm blood. CONCLUSIONS: The oxidative stress measured was significantly higher in patients undergoing CABG using modified Calafiore cardioplegia, whereas the cold cardioplegia minimised the effects of aortic clamping. The results indicate that cold cardioplegia offers superior protection of the heart, in terms of more rapid normalisation of myocardial metabolism. In elective myocardial revascularisation, intermittent antegrade warm blood cardioplegia is a comparable safe method of myocardial protection. However, in patients referring to a long clamping time, advantages of cold cardioplegia for myocardial revascularisation may be magnified.
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Soluciones Cardiopléjicas , Puente Cardiopulmonar/métodos , Puente de Arteria Coronaria , Paro Cardíaco Inducido/métodos , Miocardio/metabolismo , Anciano , Glucemia/análisis , Enfermedad Coronaria/metabolismo , Forma MB de la Creatina-Quinasa/análisis , Femenino , Glicerol/análisis , Humanos , Periodo Intraoperatorio , Lactatos/análisis , Masculino , Persona de Mediana Edad , Estrés Oxidativo , Piruvatos/análisis , Estadísticas no Paramétricas , Temperatura , Factores de TiempoRESUMEN
The subxiphoid access became the standard technique for epicardial ablation of ventricular tachycardia. However, it may prove difficult in certain situations. Here, we report an alternative method of epicardial and endocardial ablation performed via submammary minimal thoracotomy guided by pericardioscopy. Two male patients with structural heart disease and incessant ventricular tachycardia were successfully ablated using this technique. The described technique can be considered as an alternative to the standard technique. Moreover, it permits real-time visualization of cardiac vessels and fat tissue, and is safe in terms of damage to the phrenic nerve or potential bleeding complications.
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Ablación por Catéter/métodos , Endoscopía , Pericardio/cirugía , Taquicardia Ventricular/cirugía , Toracotomía , Anciano , Técnicas Electrofisiológicas Cardíacas , Humanos , Masculino , Persona de Mediana Edad , Pericardio/fisiopatología , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatología , Resultado del TratamientoRESUMEN
Transcatheter transfemoral mitral valve repair using the MitraClip system (Abbott Vascular, USA) is used in high-risk or inoperable patients with severe mitral regurgitation. We report the first-in-human simultaneous transfemoral clipping of the mitral and tricuspid valve completed by occlusion of an atrial septal defect (ASD). The procedure was performed in an 84-year-old patient in October 2015. After effective reduction of mitral and tricuspid regurgitations using the MitraClip system a PFO Occluder (St. Jude Medical, USA) was implanted. Transfemoral simultaneous mitral and tricuspid valve repair using the MitraClip system with ASD occlusion seems to be an effective therapy for high-risk or inoperable patients.
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Cardiac healing after myocardial ischemia depends on the recruitment and local expansion of myeloid cells, particularly macrophages. Here we identify Reg3ß as an essential regulator of macrophage trafficking to the damaged heart. Using mass spectrometry-based secretome analysis, we found that dedifferentiating cardiomyocytes release Reg3ß in response to the cytokine OSM, which signals through Jak1 and Stat3. Loss of Reg3ß led to a large decrease in the number of macrophages in the ischemic heart, accompanied by increased ventricular dilatation and insufficient removal of neutrophils. This defect in neutrophil removal in turn caused enhanced matrix degradation, delayed collagen deposition and increased susceptibility to cardiac rupture. Our data indicate that OSM, acting through distinct intracellular pathways, regulates both cardiomyocyte dedifferentiation and cardiomyocyte-dependent regulation of macrophage trafficking. Release of OSM from infiltrating neutrophils and macrophages initiates a positive feedback loop in which OSM-induced production of Reg3ß in cardiomyocytes attracts additional OSM-secreting macrophages. The activity of the feedback loop controls the degree of macrophage accumulation in the heart, which is instrumental in myocardial healing.
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Antígenos de Neoplasias/metabolismo , Biomarcadores de Tumor/metabolismo , Lectinas Tipo C/metabolismo , Macrófagos/metabolismo , Isquemia Miocárdica/patología , Miocardio/patología , Oncostatina M/metabolismo , Proteínas/metabolismo , Animales , Antígenos de Neoplasias/genética , Biomarcadores de Tumor/genética , Colágeno/metabolismo , Electroforesis en Gel Bidimensional , Femenino , Corazón/fisiología , Ventrículos Cardíacos/metabolismo , Inflamación , Interleucina-6/metabolismo , Lectinas Tipo C/genética , Macrófagos/citología , Masculino , Ratones , Ratones Transgénicos , Miocitos Cardíacos/metabolismo , Proteínas Asociadas a Pancreatitis , Proteínas/genética , Ratas , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction. Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become chronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead to compromised pump function and patient death. It is, therefore, of major importance to understand key events in the progression from a compensatory left ventricular (LV) systolic dysfunction to a decompensatory LV systolic dysfunction and HF. To achieve this, various animal models in combination with an "omics" toolbox can be used. These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future.