Coma-Canella, I. (Isabel)
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- The activity of circulating dipeptidyl peptidase-4 is associated with subclinical left ventricular dysfunction in patients with type 2 diabetes mellitus(2013) Huerta, A. (Ana); Lopez-Salazar, M.B. (María Begoña); Diez-Martinez, J. (Javier); Ravassa, S. (Susana); Barba, J. (Joaquín); Gonzalez, A. (Arantxa); Coma-Canella, I. (Isabel)Background: Patients with type 2 diabetes mellitus (T2DM) present subclinical left ventricular systolic and/or diastolic dysfunction (LVD). Dipeptidyl peptidase-4 (DPP4) inactivates peptides that possess cardioprotective actions. Our aim was to analyze whether the activity of circulating DPP4 is associated with echocardiographically defined LVD in asymptomatic patients with T2DM. Methods: In this cross-sectional study, we examined 83 T2DM patients with no coronary or valve heart disease and 59 age and gender-matched non-diabetic subjects. Plasma DPP4 activity (DPP4a) was measured by enzymatic assay and serum amino-terminal pro-brain natriuretic peptide (NT-proBNP) was measured by enzyme-linked immunosorbent assay. LV function was assessed by two-dimensional echocardiographic imaging, targeted M-mode recordings and Doppler ultrasound measurements. Differences in means were assessed by t-tests and one-way ANOVA. Associations were assessed by adjusted multiple linear regression and logistic regression analyses. Results: DPP4a was increased in T2DM patients as compared with non-diabetic subjects (5855 ± 1632 vs 5208 ± 957 pmol/min/mL, p < 0.05). Clinical characteristics and echocardiographic parameters assessing LV morphology were similar across DPP4a tertiles in T2DM patients. However, prevalence of LVD progressively increased across incremental DPP4a tertiles (13%, 39% and 71%, all p < 0.001). Multivariate regression analysis confirmed the independent associations of DPP4a with LVD in T2DM patients (p < 0.05). Similarly, multiple logistic regression analysis showed that an increase of 100 pmol/min/min plasma DPP4a was independently associated with an increased frequency of LVD with an adjusted odds ratio of 1.10 (95% CI, 1.04 to 1.15, p = 0.001). Conclusions: An excessive activity of circulating DPP4 is independently associated with subclinical LVD in T2DM patients. Albeit descriptive, these findings suggest that DPP4 may be involved in the mechanisms of LVD in T2DM.
- A case of capecitabine-induced coronary microspasm in a patient with rectal cancer(Baishideng Publishing Group, 2007) Martinez-Monge, R. (Rafael); Arbea-Moreno, L. (Leire); Garcia-Foncillas, J. (Jesús); Coma-Canella, I. (Isabel)5-Fluorouracil (5-FU) is the most frequently used chemotherapy agent concomitant with radiotherapy in the management of patients with rectal cancer. Capecitabine is an oral fluoropyrimidine that mimics the pharmaconkinetics of infusional 5-FU. This new drug is replacing 5-FU as a part of the combined-modality treatment of a number of gastrointestinal cancers. While cardiac events associated with the use of 5-FU are a well known side effect, capecitabine-induced cardiotoxicity has been only rarely reported. Here, we reviewed the case of a patient with rectal cancer who had a capecitabine-induced coronary vasospasm. The most prominent mutation of the dihydropyrimidine dehydrogenase gene was also analyzed.
- Los pacientes con placas coronarias vulnerables presentan mayores niveles séricos de metaloproteinasa-1(2017) Paramo, J.A. (José Antonio); Sanchez-Elvira, G. (Guillermo); Calabuig, J. (José); Barba, J. (Joaquín); Coma-Canella, I. (Isabel); Artaiz, M. (Miguel)Fundamento. Las placas ateroscleróticas que producen la mayoría de los síndromes coronarios agudos al romperse son los fibroateromas de cápsula fina, denominados placas vulnerables. Éstas pueden ser detectadas únicamente con técnicas invasivas de imagen intracoronaria. Es preciso encontrar un biomarcador no invasivo que permita identificar a los pacientes con estas placas sin necesidad de cateterismo cardiaco. La metaloproteinasa-1 es una enzima involucrada en el metabolismo de la matriz extracelular que ha sido relacionada con la ruptura de las placas ateroscleróticas. Se desconocen sus niveles séricos en pacientes con placas vulnerables. Material y métodos. Se incluyeron pacientes sometidos a cateterismo cardiaco por enfermedad coronaria estable. Se estudiaron las arterias coronarias con tomografía de coherencia óptica para detectar placas vulnerables. Se extrajeron muestras de sangre periférica y del seno coronario para analizar la concentración de metaloproteinasa-1. Resultados. Se incluyeron 51 pacientes. Trece tenían al menos un fibroateroma de cápsula fina. No se encontraron diferencias significativas en las características clínicas, perfil lipídico ni proteína C reactiva entre los pacientes con y sin placas vulnerables. Los pacientes con placas vulnerables presentaron concentraciones significativamente mayores de metaloproteinasa-1, tanto en sangre periférica (7330±5541 vs 2894±1783 pg/ml, p=0,025) como en seno coronario (6012±3854 vs 2707±1252 pg/ml, p=0,047). Conclusiones. Los pacientes con placas vulnerables presentaron niveles séricos significativamente mayores de metaloproteinasa- 1. Se requieren estudios con seguimiento clínico para evaluar el valor pronóstico de la metaloproteinasa-1 sérica.
- Insuficiencia cardíaca. Tratamiento farmacológico actual(Ediciones Universidad de Navarra, 2005) Nasarre, E. (Emilio); Coma-Canella, I. (Isabel); Castaño, S. (Sara)Treatment of heart failure (HF) has changed in recent years, despite the paucity of new approved drugs. Current treatment is directed not only towards improving symptoms, but also to preventing the development from asymptomatic systolic dysfunction to symptomatic heart failure, to preventing cardiac remodelling, renal dysfunction and to reducing mortality. The main families of drugs currently used are: cardiac glycosides, diuretics, angiotensin-converting enzyme inhibitors (ACEI), beta-blocking drugs (BB), angiotensin-II receptor blockers (ARB) and aldosterone receptor antagonists. The combination isosorbide dinitrate + hydralazine is hardly used due to its side effects and none of the new positive inotropic drugs has been approved in chronic HF, because all of them increase mortality. Levosimendan is a new positive inotropic agent approved for acute HF by an intravenous route, with a favourable effect on prognosis vs placebo and vs dobutamine (which worsens the prognosis). The approved oral drugs can be given at the same time if the patient tolerates them, because their beneficial effect is additive. Mortality in two years in mild to moderate HF is 34% with glycosides + diuretics. It falls to 22% when an ACEI is added, to 14% when a BB is added and to 10% when an aldosterone antagonist is added. ARB can be given instead of an ACEI or be added to the other drugs.
- Disminución de la reserva de flujo coronario en pacientes con insuficiencia cardíaca no isquémica(Elsevier España, 2003) Villar, L. (Luis); Marti-Climent, J.M. (Josep María); Cosin, J. (Juan); Garcia-Velloso, M. J. (María José); Macias, A. (Alfonso); Coma-Canella, I. (Isabel); Artaiz, M. (Miguel)Introduction and objectives. Coronary flow reserve (CFR) is impaired not only in ischemic heart disease, but also in cardiac diseases that may or may not course with heart failure. The aim of the present study was to determine if the severity of heart failure can influence CFR impairment. Methods. Forty patients with non-ischemic heart disease and heart failure were studied 41 times. Four groups were established: 1. 10 patients in functional class III-IV; 2. 10 patients in functional class II not taking beta-blockers; 3. 11 patients in class II treated with carvedilol, and 4. 10 patients in class I. These patients had a history of heart failure and systolic dysfunction. Myocardial blood flow (MBF) was measured with positron emission tomography (PET) and N-13 ammonia at rest (r) and during adenosine triphosphate (ATP) infusion. Results. MBF and CFR were significantly higher in group 4 (1.95 ± 0.58 and 2.40 ± 0.95 ml/min/g) than in group 1 (1.02 ± 0.52 and 1.46 ± 0.48 ml/min/g). CFR tended to be higher in groups 2 (1.73 ± 0.72), and 3 (1.89 ± 0.75) vs group 1. No significant correlation was found between CFR and the following variables: age, systolic blood pressure, ventricular mass index, ventricular volume indexes, and ejection fraction. Conclusions. Coronary microvascular function is impaired in non-ischemic heart failure, and the impairment is related to functional class, regardless of the underlying responsible heart disease.
- Neurohormonas y citocinas en la insuficiencia cardíaca. Correlación con la reserva de flujo coronario(Elsevier España, 2005) Macias, A. (Alfonso); Coma-Canella, I. (Isabel); Sanchez-Ibarrola, A. (Alfonso); Varo-Cenarruzabeitia, M.N. (Miren Nerea)Introduction and objectives. In heart failure, the coronary flow reserve (CFR) measured by positron-emission tomography (PET) is reduced. As neurohormone and cytokine levels are also altered in patients with the condition, our aim was to determine whether there is a correlation between CFR and neurohormone and cytokine levels. Patients and method. The study included 40 patients with heart failure but without ischemic heart disease. Myocardial blood flow was measured by PET using nitrogen- 13 ammonia at baseline and during ATP infusion. The CFR was calculated for each patient. In addition, levels of the following were determined: norepinephrine, endothelin- 1, angiotensin-II, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), tumor necrosis factor-alpha, interleukin (IL)-1β, soluble IL-2 receptor, and IL-6. Results. All neurohormone levels were elevated above reference values. The levels of all cytokines, except IL-1β, were also elevated. There was a significant negative correlation between CFR and the levels of several neurohormones: ANP (r=–0.476), BNP (r=–0.442), and IL-6 (r=–0.509). Conclusions. In heart failure, the decrease in CFR is correlated with increases in the levels of certain neurohormones (i.e., ANP and BNP) and cytokines (i.e., IL-6), with vasodilatory effect. These increases are probably are related to compensatory mechanisms that are unable to correct for the endothelial dysfunction present in these patients.
- Increased thrombin generation after acute versus chronic coronary disease as assessed by the thrombin generation test(Schattauer, 2008) Paramo, J.A. (José Antonio); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Serrano, R. (Rosario); Coma-Canella, I. (Isabel); Martinez-de-Lizarrondo, S. (Sara); Zudaire, M. (Maite)Atherosclerosis is the most common pathophysiologic substrate of coronary artery disease (CAD). Whereas plaque progression and arterial remodeling are critical components in chronic CAD, intracoronary thrombosis over plaque disruption is causally related to acute CAD. It was the objective of this study to investigate the differences between prior acute CAD and chronic CAD by a simple global coagulation assay measuring thrombin generation. A cross-sectional study involving 15 healthy controls, 35 patients with chronic stable CAD, and 60 patients after an episode of acute myocardial infarction (AMI) was performed. Thrombin generation was measured between three and 11 months after the initial diagnosis (mean 6 months) by a commercially available fluorogenic assay (Technothrombin TGA). In each patient the lag phase, velocity index and peak thrombin were obtained from the thrombogram profile. Traditional cardiovascular risk factors were recorded, and the inflammatory markers, fibrinogen and hs-C-reactive protein were determined. Compared with stable CAD patients, showing normal thrombograms, those with previous AMI showed earlier lag phase (p < 0.05) and significant increase of both the velocity index (p < 0.001) and peak thrombin (p < 0.05), indicating faster and higher thrombin generation in the AMI group. Differences in thrombin generation between stable and acute CAD patients remained significant (p < 0.001) after adjusting for conventional CAD risk factors (age, gender, diabetes, hypertension, smoking, and hypercholesterolemia). In conclusion, patients with a previous history of acute CAD showed earlier, faster and higher thrombin generation than stable chronic CAD patients. The thrombin generation test may be of clinical value to monitor hypercoagulable/vulnerable blood and/or guide therapy in CAD.
- Técnica de primera elección para la valoración de la viabilidad miocárdica. Gammagrafía cardiaca de perfusión(Elsevier España, 1998) Coma-Canella, I. (Isabel)Stress echocardiography and perfusion scintigraphy are both useful techniques in the assessment of myocardial viability. The use of one technique or the other as the first choice test depends mainly on each hospital’s experience. Perfusion scintigraphy should be chosen as the first technique in the following situations: a) hospitals with little experience in stress echocardiography and a good Nuclear Medicine department; b) patients with a bad acoustic window in rest echocardiography; c) contraindication of a high dobutamine dose, and d) need of quantification of viable area. When having chosen echocardiography as the first technique, perfusion scintigraphy is indicated when the response to dobutamine of the asynergic area does not allow the confirmation or the rejection of the presence of viability.
- Modificaciones de la función ventricular izquierda con dosis crecientes de dobutamina en individuos sanos(Elsevier España, 1999) Maceira, A.M. (Alicia M.); Garcia-Velloso, M. J. (María José); Cabrera, A. (A.); Albaladejo, V.J. (V.J.); Coma-Canella, I. (Isabel)E1 objetivo fue valorar los cambios de la función ventricular con dosis crecientes de dobutamina en jóvenes sanos. Se realizó ventriculografía isotópica en situación basal, con dosis baja (10 µg/Kg/min) y alta (40 µg/Kg/min) del fármaco. Se estudiaron la fracción de eyección global, segmentaria y del primer tercio de la sístole, la velocidad máxima de llenado diastólico y el tiempo hasta la velocidad máxima de llenado. Se observó un aumento progresivo de la fracción de eyección global con las dosis sucesivas del fármaco. La fracción de eyección segmentaria, fracción de eyección del primer tercio de la sístole y la velocidad máxima de llenado aumentaron con la dosis baja sin mostrar diferencias con la alta. Se concluye que la dobutamina en jóvenes sanos y en estas dosis induce un aumento significativo de todos los parámetros sistólicos y de la velocidad máxima de llenado, sin modificar el tiempo hasta la velocidad máxima de llenado.
- Captación de Talio-201 en pulmón y corazón con diferentes tipos de estrés. Estudio en voluntarios sanos(Elsevier España, 1999) Maceira, A.M. (Alicia M.); Richter, J.A. (José Ángel); Garcia-Velloso, M. J. (María José); Cabrera, A. (A.); Albaladejo, V.J. (V.J.); Coma-Canella, I. (Isabel)Para comprobar si existen diferencias en la captación pulmonar y miocárdica de Talio-201 entre distintos tipos de estrés se estudiaron 40 voluntarios varones de edad 21,7 ± 0,9 años. A todos se les practicó una gammagrafía de perfusión miocárdica con Talio-201 mediante SPECT. Los 40 individuos fueron aleatorizados en 4 grupos de 10 sujetos cada uno, siendo cada grupo sometido a un tipo de estrés: ejercicio físico, dobutamina, dipiridamol y adenosina trifosfato (ATP). Se observaron diferencias significativas en la captación pulmonar y cardíaca del isótopo, siendo ambas menores con ejercicio físico que con los tres tipos de estrés farmacológico; el índice pulmón/corazón fue equivalente en los cuatro grupos. Se concluye que, aunque el ejercicio físico induce una menor captación pulmonar y cardíaca de Talio-201 que el estrés farmacológico, el índice pulmón/corazón es equivalente para los cuatro grupos y de un valor de 0,28 ± 0,03 en individuos jóvenes sanos