Rabago, G. (Gregorio)

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    Autologous intramyocardial injection of cultured skeletal muscle-derived stem cells in patients with non-acute myocardial infarction
    (Oxford University Press, 2003) Herreros, J. (Jesús); Cañizo, C. (C.) del; Marti-Climent, J.M. (Josep María); Gonzalez-Santos, J.M. (José María); Gavira, J.J. (Juan José); Sanchez, P.L. (Pedro L.); Alegria, E. (Eduardo); Martin-Luengo, C. (Cándido); Lopez-Holgado, N. (Natalia); Barba, J. (Joaquín); Garcia-Velloso, M. J. (María José); Hernandez, M. (Milagros); Rabago, G. (Gregorio); Prosper-Cardoso, F. (Felipe); Perez, A. (Ana)
    AIM: Experimental animal studies suggest that the use of skeletal myoblast in patients with myocardial infarction may result in improved cardiac function. The aim of the study was to assess the feasibility and safety of this therapy in patients with myocardial infarction. METHODS AND RESULTS: Twelve patients with old myocardial infarction and ischaemic coronary artery disease underwent treatment with coronary artery bypass surgery and intramyocardial injection of autologous skeletal myoblasts obtained from a muscle biopsy of vastus lateralis and cultured with autologous serum for 3 weeks. Global and regional cardiac function was assessed by 2D and ABD echocardiogram. 18F-FDG and 13N-ammonia PET studies were used to determine perfusion and viability. Left ventricular ejection fraction (LVEF) improved from 35.5+/-2.3% before surgery to 53.5+/-4.98% at 3 months (P=0.002). Echocardiography revealed a marked improvement in regional contractility in those cardiac segments treated with skeletal myoblast (wall motion score index 2.64+/-0.13 at baseline vs 1.64+/-0.16 at 3 months P=0.0001). Quantitative 18F-FDG PET studies showed a significant (P=0.012) increased in cardiac viability in the infarct zone 3 months after surgery. No statistically significant differences were found in 13N-ammonia PET studies. Skeletal myoblast implant was not associated with an increase in adverse events. No cardiac arrhythmias were detected during early follow-up. CONCLUSIONS: In patients with old myocardial infarction, treatment with skeletal myoblast in conjunction with coronary artery bypass is safe and feasible and is associated with an increased global and regional left ventricular function,improvement in the viability of cardiac tissue in the infarct area and no induction of arrhythmias.
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    Association of cystatin C with heart failure with preserved ejection fraction in elderly hypertensive patients: potential role of altered collagen metabolism
    (Lippincott Williams & Wilkins, 2016) Huerta, A. (Ana); Brugnolaro, C. (Cristina); Beloqui, O. (Óscar); Zubillaga, E. (Elena); Querejeta, R. (Ramón); Ravassa, S. (Susana); Gonzalez, A. (Arantxa); Rabago, G. (Gregorio); San-Jose, G. (Gorka); López, B. (Begoña); Diez, J. (Javier)
    Objectives: Cystatin C has been shown to be associated with heart failure with preserved ejection fraction (HFPEF). In addition, myocardial fibrosis has been involved in diastolic dysfunction in HFPEF. Therefore, we hypothesized that increased cystatin C levels may be associated with altered collagen metabolism, contributing to diastolic dysfunction in patients with HFPEF. Methods: One hundred and forty-one elderly hypertensive patients with HFPEF were included. Cardiac morphology and function was assessed by echocardiography. Circulating levels of cystatin C, biomarkers of collagen type I synthesis (carboxy-terminal propeptide of procollagen type I) and degradation [matrix metalloproteinase-1 (MMP- 1) and its inhibitor TIMP-1] and osteopontin were analyzed by ELISA. Twenty elderly sex-matched patients with no identifiable cardiac disease were used as controls. In-vitro studies were performed in human cardiac fibroblasts. Results: Compared with controls, cystatin C was increased (P < 0.001) in patients with HFPEF, even in those with a normal estimated glomerular filtration rate (eGFR; P < 0.05). Cystatin C was directly correlated with the estimated pulmonary capillary wedge pressure (P < 0.01), TIMP-1 and osteopontin (P < 0.001) and inversely correlated with MMP-1:TIMP-1 (P < 0.01), but not with carboxy-terminal propeptide of procollagen type I or MMP- 1 in all patients with HFPEF. These associations were independent of eGFR. In vitro, osteopontin (P < 0.01) and TIMP-1 (P < 0.001) increased in the supernatant of cardiac fibroblasts exposed to cystatin C. Conclusion: In patients with HFPEF of hypertensive origin, cystatin C is increased and associated with diastolic dysfunction and alterations in collagen metabolism independently of eGFR. An excess of cystatin C might contribute to diastolic dysfunction in HFPEF by facilitating myocardial fibrosis via accumulation of osteopontin and TIMP-1.
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    Long-term prognostic value of coronary CTA in orthotopic heart transplant recipients
    (ARRS, 2021) García-Baizán, A. (Alejandra); Bastarrika, G. (Gorka); Gavira, J.J. (Juan José); Ezponda, A. (Ana); Rabago, G. (Gregorio); Caballeros, M. (Meylin); Manrique, R. (Rebeca)
    OBJECTIVE. This study aimed to evaluate the long-term prognostic value of coronary CTA (CCTA) in heart transplant recipients. MATERIALS AND METHODS. The records of 114 patients who had undergone a heart transplant (mean age, 61.7 ± 11.1 [SD] years; 83.3% men) and who underwent CCTA for the surveillance of coronary allograft vasculopathy (CAV) from June 2007 to December 2017 were retrospectively evaluated for the occurrence of major adverse cardiovascular events (MACEs) (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, coronary revascularization, cardiac arrhythmias, stroke, and retransplant). Patients were classified according to the presence of nonobstructive CAV (lumen reduction < 50%) or obstructive disease (lumen reduction ≥ 50%) and using a coronary segment involvement score (SIS). Differences in MACE rate between groups were compared. RESULTS. Obstructive CAV was observed in 12 heart transplant recipients (10.5%). During a mean follow-up of 67.5 ± 41.4 months the overall rates of MACE were 50% and 14.7% in patients with obstructive and nonobstructive CAV, respectively (p < .05), resulting in an odds ratio for MACE of 6 (95% CI, 1.7–21.2). Comparison of event-free survival showed a hazard ratio (HR) of 5 (95% CI, 1.95–13; p =. 004) for patients with obstructive disease. The presence of four or more stenotic coronary segments (SIS ≥ 4) was associated with a higher rate of events (HR, 3.46; 95% CI, 1.46–8.23). CONCLUSION. In patients who have undergone a heart transplant, CCTA offers a significant long-term prognostic impact on the prediction of MACEs.
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    Giant left atrial thrombus 17 years after orthotopic heart transplantation
    (Oxford University Press, 2010) Bastarrika, G. (Gorka); Dell’Aquila, A.M. (Angelo Maria); Levy-Praschker, B.G. (Beltran G.); Rabago, G. (Gregorio)
    We present the case of a 66-year-old woman who underwent orthotopic heart transplantation 17 years earlier for dilated cardiomyopathy. After 7 years allograft coronary vasculopathy developed requiring coronary artery angioplasty. In year 15 postoperatively she experienced congestive heart failure and she became symptomatic requiring diuretics and digoxin treatment. In year 16 postoperatively a routine coronary computed tomography (CT) angiography study revealed a giant thrombus in the left atrium. The patient had had no thromboembolicrelated symptoms. Anticoagulation therapy was introduced and the patient has not presented any thromboembolic-related complication. As the symptoms of cardiac insufficiency worsened we decided to evaluate the patient for re-transplantation.
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    Chronic aneurysm of the descending thoracic aorta presenting with right pleural effusion and left phrenic paralysis
    (Texas Heart Institute, 1999) Lopez-Coronado, J.L. (José Luis); Rabago, G. (Gregorio); Martin-Trenor, A. (Alejandro)
    A 62-year-old man was admitted to the emergency department with chronic dysphagia and lower back pain. Chest radiography revealed a wide mediastinal shadow and an elevated left diaphragm, which proved to be secondary to left phrenic paralysis. The patient was diagnosed with an aneurysm of the descending thoracic aorta and was admitted to the hospital. After the patient was admitted, the aneurysm ruptured into the right chest. The patient underwent an emergency operation to replace the ruptured segment with a synthetic graft. Postoperative recovery and follow-up were uneventful. This report describes an unusual presentation of a thoracic aortic aneurysm. Hemidiaphragmatic paralysis caused by compression of the phrenic nerve is an unusual complication that, to our knowledge, has not been previously reported.
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    Utilización de células madre en terapia regenerativa cardíaca
    (Servicio de Publicaciones de la Universidad de Navarra, 2002) Herreros, J. (Jesús); Hernández, M. (M.); Rifon, J. J. (Jose J.); Rocha, E. (Eduardo); Cosin, J. (Juan); Inoges, S. (Susana); Perez-Calvo, J. (Javier); Rabago, G. (Gregorio); Panizo, A. (Ángel); Prosper-Cardoso, F. (Felipe); Perez, A. (Ana)
    One of the most important challenges in modern medicine is the use of stem cells for the treatment of human disease such as diabetes, Parkinson ́s disease or isquemic cardiomyopathy. A number of problems need to be solved before stem cells can be applied clinically. In this paper we will review some concepts related to the potential of stem cells, focusing on adult stem cells as they have recently been described by the group of Catherine Verfaillie. We will also present our initial clinical results using adult stem cells for cardiac regenerative therapy. In the studies mentioned above, autologous muscle stem cells (satelite cells) were infused directly in the periphery of the scar tissue of the infarct. We describe the technique for ex vivo expansion and purification of muscle stem cells.
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    Incidence and prognosis of colorectal cancer after heart transplantation: data from the Spanish Post-Heart Transplant Tumor Registry
    (2023) Muñiz, J. (Javier); Almenar-Bonet, L. (Luis); Gómez, M. (Manuel); Blasco-Peiro, T. (Teresa); García-Romero, E. (Elena); Garrido-Bravo, I. (Iris); Fuente-Galán, L. (Luis) de la; Sobrino-Márquez, J.M. (Jose M.); Morán, L. (Laura); López-Granados, A. (Amador); Rabago, G. (Gregorio); González-Vílchez, F. (Francisco); Castel-Lavilla, M.A. (Maria Angels); Díaz-Molina, B. (Beatriz); Blázquez-Bermejo, Z. (Zorba); Sagastagoitia-Fornie, M. (Marta); Crespo-Leiro, M.G. (María G.); Mirabet-Pérez, S. (Sonia)
    In this observational and multicenter study, that included all patients who underwent a heart transplantation (HT) in Spain from 1984 to 2018, we analyzed the incidence, management, and prognosis of colorectal cancer (CRC) after HT. Of 6,244 patients with a HT and a median follow-up of 8.8 years since the procedure, 116 CRC cases (11.5% of noncutaneous solid cancers other than lymphoma registered) were diagnosed, mainly adenocarcinomas, after a mean of 9.3 years post-HT. The incidence of CRC increased with age at HT from 56.6 per 100,000 person-years among under 45 year olds to 436.4 per 100,000 person-years among over 64 year olds. The incidence rates for age-at-diagnosis groups were significantly greater than those estimated for the general Spanish population. Curative surgery, performed for 62 of 74 operable tumors, increased the probability of patient survival since a diagnosis of CRC, from 31.6% to 75.7% at 2 years, and from 15.8% to 48.6% at 5 years, compared to patients with inoperable tumors. Our results suggest that the incidence of CRC among HT patients is greater than in the general population, increasing with age at HT.
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    Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed
    (Elsevier, 2003) Belzunce, M. (Miriam); Paramo, J.A. (José Antonio); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Fernandez-Alonso, L. (Leopoldo); Monasterio, A. (Alberto); Rabago, G. (Gregorio); Roncal, C. (Carmen)
    BACKGROUND: Proteolytic imbalance might determine arterial remodeling and plaque destabilization in atherosclerotic vessels. The aim of this study was to examine differences in the patterns of metalloproteinases (MMPs) and MMP inhibitor (TIMP-1) expression in advanced human atheromas, both in relation to the plaque features and the vascular bed involved. METHODS AND RESULTS: Immunohistochemistry for MMP-1, -3, -9 and TIMP-1 as well as the collagen content were measured in vascular sections from patients undergoing peripheral revascularization (carotid n=11, femoral n=23) and aorto-coronary bypass surgery (mammary arteries n=20, as controls). Increased expression of all MMPs was detected in atherosclerotic as compared with control sections (P<0.01). Aneurysmal plaques showed a significant increase of MMP-1 and-3 and a reduction in total collagen (P<0.05) in relation to occlusive lesions. Calcification areas in atherosclerotic plaques were consistently associated with increased TIMP-1 expression (P<0.01). Finally, MMP-9 expression was higher in occlusive lesions from carotid than femoral arteries (P<0.01). CONCLUSIONS: Aneurysm lesions expressed higher MMP-1 and-3 expression than occlusive plaques, and MMP-9 was mainly detected in carotid as compared with femoral arteries. TIMP-1 was associated with arterial calcification. These differences in the MMPs/TIMP-1 expression might determine the evolution of advanced atherosclerotic plaques and contribute to its vulnerability.
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    Cirugía de la fibrilación auricular
    (Gobierno de Navarra. Departamento de Salud, 2011-01) Hernandez-Estefania, R. (Rafael); Levy-Praschker, B.G. (Beltran G.); Rabago, G. (Gregorio); Martin-Trenor, A. (Alejandro)
    Atrial fibrillation surgery is based on creating scars in the atrium, in order to avoid re-entry phenomena that may initiate and perpetuate arrhythmia, and driving the normal stimuli from the sinus node to the atrio-ventricular node. The complexity and increased risk of the initial surgical technique, based on a "cut-and-sew" procedure, have enhanced other current procedures, in which different energies are used making it possible to perform scars in a safer and less invasive way. At present, atrial fibrillation surgery is not performed routinely in all cardiothoracic surgical centers, and there is no consensus in which is the best type of technique. Even if the results are good, they depend on multiples factors such as duration of arrhythmia, atrial size and type of technique employed. In addition, there is some variability in the description within the scientific community of the results and procedures used, which makes its analysis confusing. In this paper we review the different techniques described, the results and their application in minimally invasive surgery.
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    Combined surgical approach for sarcoma lung metastasis with atrial involvement
    (Georg Thieme Verlag, 1999) Torre, W. (Wenceslao); Baixauli-Fons, J. (Jorge); Sierrasesumaga, L. (Luis); Barba, J. (Joaquín); Rabago, G. (Gregorio); Galbis, J.M. (J. M.)
    A 20-year-old patient, who had been treated for a femur sarcoma with pulmonary metastases 8 years before, arrived at our institution with a new metastatic hilar lung nodule. During the standard lobectomy procedure an unexpected atrial invasion by the tumor was discovered. Intraoperative transesophageal echocardiography (TEE) showed a big pediculated tumor in the atrium. Cardiopulmonary bypass (CPB) was required in order to safely resect the atrial wall with the tumor. The atrial defect was repaired with a pericardial patch. Postoperative course was uneventful. After 14 months, the patient is asymptomatic and free of disease.