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Type-2 diabetes (T2DM) and arterial hypertension (HTN) are major risk factors for heart failure. Importantly, these pathologies could induce synergetic alterations in the heart, and the discovery of key common molecular signaling may suggest new targets for therapy. Intraoperative cardiac biopsies were obtained from patients with coronary heart disease and preserved systolic function, with or without HTN and/or T2DM, who underwent coronary artery bypass grafting (CABG). Control (n = 5), HTN (n = 7), and HTN + T2DM (n = 7) samples were analysed by proteomics and bioinformatics. Additionally, cultured rat cardiomyocytes were used for the analysis (protein level and activation, mRNA expression, and bioenergetic performance) of key molecular mediators under stimulation of main components of HTN and T2DM (high glucose and/or fatty acids and angiotensin-II). As results, in cardiac biopsies, we found significant alterations of 677 proteins and after filtering for non-cardiac factors, 529 and 41 were changed in HTN-T2DM and in HTN subjects, respectively, against the control. Interestingly, 81% of proteins in HTN-T2DM were distinct from HTN, while 95% from HTN were common with HTN-T2DM. In addition, 78 factors were differentially expressed in HTN-T2DM against HTN, predominantly downregulated proteins of mitochondrial respiration and lipid oxidation. Bioinformatic analyses suggested the implication of mTOR signaling and reduction of AMPK and PPARα activation, and regulation of PGC1α, fatty acid oxidation, and oxidative phosphorylation. In cultured cardiomyocytes, an excess of the palmitate activated mTORC1 complex and subsequent attenuation of PGC1α-PPARα transcription of ß-oxidation and mitochondrial electron chain factors affect mitochondrial/glycolytic ATP synthesis. Silencing of PGC1α further reduced total ATP and both mitochondrial and glycolytic ATP. Thus, the coexistence of HTN and T2DM induced higher alterations in cardiac proteins than HTN. HTN-T2DM subjects exhibited a marked downregulation of mitochondrial respiration and lipid metabolism and the mTORC1-PGC1α-PPARα axis might account as a target for therapeutical strategies.
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Diabetes Mellitus Tipo 2 , Hipertensión , Humanos , Ratas , Animales , PPAR alfa/genética , PPAR alfa/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Hipertensión/complicaciones , Hipertensión/genética , Hipertensión/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Miocitos Cardíacos/metabolismo , Adenosina Trifosfato/metabolismoRESUMEN
OBJECTIVES: Patient-prosthesis mismatch has been identified as a risk factor for mortality after aortic valve replacement and for structural valve deterioration (SVD) in patients receiving a bioprosthetic aortic valve. The aim of the present study was to compare the incidence of aortic valve bioprosthesis replacement for SVD in patients with mismatch to a population without mismatch. METHODS: Three hundred eighty-seven adult patients who underwent aortic valve replacement with a bioprosthesis from 1974 to 2009 were retrospectively reviewed. Mismatch was considered to be present if the anticipated indexed effective orifice area was <0.70 cm(2) /m(2) . The median follow-up period was 7.2 years. Follow-up was 97% complete. RESULTS: Patient-prosthesis mismatch was present in 12% of the study population (n = 47). Ten-year freedom from reoperation for aortic bioprosthesis replacement was 74.3 ± 3.2%. During follow-up, 111 patients underwent reoperation for aortic bioprosthesis replacement. Causes of aortic bioprosthesis replacement were SVD of the bioprosthesis (n = 96), paravalvular leak (n = 10), and acute endocarditis (n = 5). According to unadjusted Kaplan-Meier analysis, patients with mismatch had a higher incidence of aortic bioprosthesis replacement for SVD when compared with patients without mismatch (log rank test: p 0.05). This result was confirmed by multivariable Cox regression analysis, which identified two independent predictors of aortic bioprosthesis replacement for SVD: patients' age (hazard ratio (HR) 0.967) and patient-prosthesis mismatch (HR 2.161). CONCLUSION: Patients suffering from mismatch were twice as likely to undergo reoperation for aortic bioprosthesis replacement for SVD than those without mismatch.
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Válvula Aórtica/cirugía , Bioprótesis/efectos adversos , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Prótesis Valvulares Cardíacas/efectos adversos , Diseño de Prótesis , Falla de Prótesis/etiología , Adulto , Anciano , Anciano de 80 o más Años , Bioprótesis/estadística & datos numéricos , Femenino , Estudios de Seguimiento , Implantación de Prótesis de Válvulas Cardíacas/estadística & datos numéricos , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Reoperación/estadística & datos numéricos , Riesgo , Factores de Riesgo , Factores de TiempoRESUMEN
Introduction: The presence of non-coronary atherosclerosis (NCA) in patients with coronary artery disease is associated with a poor prognosis. We have studied whether NCA is also a predictor of poorer outcomes in patients undergoing coronary artery bypass grafting (CABG). Materials and methods: This is an observational study involving 567 consecutive patients who underwent CABG. Variables and prognosis were analysed based on the presence or absence of NCA, defined as previous stroke, transient ischaemic attack (TIA), or peripheral artery disease (PAD) [lower extremity artery disease (LEAD), carotid disease, previous lower limb vascular surgery, or abdominal aortic aneurysm (AAA)]. The primary outcome was a combination of TIA/stroke, acute myocardial infarction, new revascularization procedure, or death. The secondary outcome added the need for LEAD revascularization or AAA surgery. Results: One-hundred thirty-eight patients (24%) had NCA. Among them, traditional cardiovascular risk factors and older age were more frequently present. At multivariate analysis, NCA [hazard ratio (HR) = 1.84, 95% confidence interval (CI) 1.27-2.69], age (HR = 1.35, 95% CI 1.09-1.67, p = 0.004), and diabetes mellitus (HR = 1.50, 95% CI 1.05-2.15, p = 0.025), were positively associated with the development of the primary outcome, while estimated glomerular filtration rate (HR = 0.86, 95% CI 0.80-0.93, p = 0.001) and use of left internal mammary artery (HR = 0.36, 95% CI 0.15-0.82, p = 0.035), were inversely associated with this outcome. NCA was also an independent predictor of the secondary outcome. Mortality was also higher in NCA patients (27.5% vs. 9%, p < 0.001). Conclusions: Among patients undergoing CABG, the presence of NCA doubled the risk of developing cardiovascular events, and it was associated with higher mortality.
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BACKGROUND: A National Spanish Registry to compile all patients treated with high intensity focused ultrasound (HIFU) energy for atrial fibrillation (AF) was created to evaluate the safety and efficacy of AF surgical ablation. METHODS: A national Spanish registry was created, and ten hospitals using HIFU to ablate AF joined it. A total of 412 patients undergoing cardiac surgery between 2006 and February 2013 were included. AF was divided between paroxysmal AF (33%) and persistent AF (67%) with a mean AF duration of 29.3±108.2 months. Mean left atrial diameter was 51.2±6.5 mm. Mean underlying heart disease were aortic valve disease (49.3%), ischemic disease (25.2%) and mitral disease (33.2%) Clinical follow-up of patients and a 6 months postoperative echocardiogram were performed in all patients. RESULTS: A pacemaker implantation was needed in 4.9% of patients with a perioperative stroke in 2.5%. Rhythm at discharge from hospital was sinus rhythm in 58%, AF in 35.9% and atrial flutter in 0.8% of patients. Sinus rhythm restoration at 6, 12, 24 and 36 months follow-up was achieved in 66.1%, 63.8%, 63.9% and 45.9% of patients respectively. Multivariate analysis showed paroxysmal AF and sinus rhythm restoration in the operating theatre as factors related to sinus rhythm long term restoration. CONCLUSIONS: The Spanish national registry showed an efficacy of AF ablation with the HIFU Epicor system of 66.1%, 63.8%, 63.9% and 45.9% at 6, 12, 24 and 36 months follow-up. There were no device-related complications.
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Fibrilación Atrial/epidemiología , Fibrilación Atrial/terapia , Procedimientos Quirúrgicos Cardíacos/estadística & datos numéricos , Ultrasonido Enfocado de Alta Intensidad de Ablación/estadística & datos numéricos , Anciano , Fibrilación Atrial/diagnóstico por imagen , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Ecocardiografía , Femenino , Ultrasonido Enfocado de Alta Intensidad de Ablación/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial , Sistema de Registros , España/epidemiología , Resultado del TratamientoRESUMEN
Cardiac transplantation has been rarely performed in patients with infective endocarditis. A 31-year-old man developed aortic endocarditis due to Brucella melitensis. He presented with fever and developed acute myocardial infarct, severe aortic regurgitation, and heart failure. Aortic valve replacement did not improve cardiac function; hence, an emergent cardiac transplantation was carried out. Eighteen years later, he is doing well and living an active and productive life. Only 6 patients have received a cardiac transplant as part of the treatment of active infective endocarditis. This patient shows how cardiac transplantation may be successfully used as salvage therapy for patients with infective endocarditis who are not candidates for valve replacement or have severe and irreversible myocardial damage.
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Brucella melitensis , Brucelosis/cirugía , Endocarditis Bacteriana/cirugía , Trasplante de Corazón , Adulto , Humanos , Masculino , Sobrevivientes , Factores de TiempoRESUMEN
INTRODUCTION AND OBJECTIVES: The relationship between the annual number of cardiac procedures at a particular center (i.e., volume) and surgical outcome is controversial. Several studies in western countries indicate that there is an inverse relationship between surgical volume and mortality. We studied the number of procedures carried out at several cardiac surgery units in Spain and their relationship to overall and risk-adjusted mortality. METHODS: This prospective observational study carried out in 6054 patients undergoing cardiac surgery at 16 hospitals represents 34% of all cardiac surgery performed in Spain during 2004. Data on risk factors and outcomes for each patient treated at participating institutions were analyzed. Data from each center were checked by an external referee. Surgical risk was evaluated for each patient using the Parsonnet and EuroSCORE methods, with the aim of determining risk-adjusted mortality. RESULTS: Overall mortality was 7.7% (95% confidence interval, 7.0%-8.4%). The risk-adjusted mortality index was calculated to be 0.81 using the Parsonnet method, and 1.12 using EuroSCORE. The Pearson correlation coefficient for the relationship between the number of procedures carried out at a center and mortality was 0.065 for overall mortality, 0.092 for risk-adjusted mortality (Parsonnet method), and 0.111 for risk-adjusted mortality (EuroSCORE method). After discarding data from the two centers with highest and lowest mortality rates, respectively, the correlations were -0.464, -0.420 and -0.267, respectively. CONCLUSIONS: No statistically significant relationship was found between the number of cardiac procedures carried out at a particular center in Spain and inhospital mortality.